The Clinician's Guide to Dermatologic Differential Diagnosis 3030635260, 9783030635268

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Paul I. Schneiderman Marc E. Grossman

The Clinician’s Guide to Dermatologic Differential Diagnosis Second Edition

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The Clinician’s Guide to Dermatologic Differential Diagnosis

Paul I. Schneiderman • Marc E. Grossman

The Clinician’s Guide to Dermatologic Differential Diagnosis Second Edition

Paul I. Schneiderman Clinical Professor of Dermatology Columbia University New York, NY USA

Marc E. Grossman Associate Clinical Professor of Dermatology Department of Dermatology Yale University School of Medicine New Haven, CT USA Adjunct Clinical Professor of Dermatology Department of Dermatology Hofstra/Northwell Donald and Barbara Zucker School of Medicine New Hyde Park, NY USA

ISBN 978-3-030-63526-8    ISBN 978-3-030-63527-5 (eBook) https://doi.org/10.1007/978-3-030-63527-5 © Springer Nature Switzerland AG 2022 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

There are a great number of people who made significant contributions to my personal and professional development, provided me with nurturing love and guidance, the opportunity to succeed, mentorship and encouragement, and valuable professional support which has enabled me to make a difference for my patients and my specialty. I am deeply grateful and indebted to them all. It is to these members of my life family that this book is lovingly dedicated. Miriam and Morris Schneiderman Steven and Arthur Schneiderman Judy Schneiderman Hyman Karmen Arthur and Marcia Karmen Etta and Louis Biblowitz Iris and Jerry Schwartzbaum Kenneth Barnett, PhD Eric Tash Bette Schneiderman Andy and Scott Schneiderman Judy and Morty Eydenberg John J. Gullo, MD Robert O. Knapp, MD Frank Call, MD Edward W. Hook, MD

Dwight Wooster, MD David Stone, MD Kenneth E. Greer, MD Richard L. Edelson, MD Barry S. Coller, MD Edward P. Cawley, MD Louis E. Harman, MD Peyton E. Weary, MD Larry Legum, MD Steven R, Kohn, MD Larry Bilsky, MD Lindy Peta Fox, MD Kristin Magnuson Nord, MD Nicole LeBoeuf, MD My co-author Marc E. Grossman, MD, FACP Paul I. Schneiderman

To Alexander and Natalie For bringing pure joy to my life Marc E. Grossman

Preface to the Second Edition

More than a decade has passed since the publication of the first edition of this textbook, A Clinician’s Guide to Dermatologic Differential Diagnosis. In that period of time, the medical literature has expanded exponentially in print and online. We have updated, edited, and incorporated new material into all of the “old chapters” of the Text. Almost a hundred additional new chapters have been added to the text. The expansion of topics was mostly the cutaneous manifestations of systemic disorders of the subspecialties of medicine and surgery for the adult and pediatric patient. The atlas has been improved and expanded. All the new images are 20% larger, making them easier to visualize, with more emphasis on morphologic detail to increase diagnostic acumen. The fine points of the physical examination enable the pictures to do the teaching. This second edition atlas contains 6000 completely new and different images from the 4000 original non-digital photographs of the first edition. Some of the new illustrations are different views or perspectives of the diagnostic images, different time periods in the evolution of skin disease, or more complete images of the entire patient providing high-­ power and low-power or scanning views of the clinical disorder represented. On a personal note, the atlas contains the only published photograph of the first case of cutaneous anthrax as a weapon of bioterrorism in New York City in 2001 (diagnosed, photographed, and treated by the author MG). Our collection of photographs of Nazi concentration camp serial identification number tattoos on the left forearms of survivors will outlive our patients and memorialize the Holocaust for the six million. The original concepts, expectations, and usefulness of our textbook have been confirmed by its continued value as a reference in the hospital, in the classroom, and in the office by the seasoned practitioner, the resident, and medical student. The first edition passed the “use test.” The correct dermatologic diagnosis is essential for the treatment to be effective. Starting with a symptom, sign, or organ system dysfunction from the table of contents, a perusal of the differential diagnosis lists has successfully led us to a diagnosis we had not considered beforehand. The text provides the essential comprehensive differential diagnosis to avoid diagnostic traps and errors of dermatologic heuristics (cognitive shortcuts). The atlas augments visual observational skills by providing focused photographs of characteristic findings in common and exotic diseases. Common findings in rare diseases and rare or unusual findings in common diseases are illustrated as well as atypical locations for both. For the patient that defies diagnosis, going systematically through check lists of diseases ensures that none is missed before concluding that the patient has a new or undescribed disorder, or that the rash has not yet evolved into its recognizable form. Writing and editing the “Red Books” have been as much self-education for us as teaching has been for us over the past 40 years. Education is a lifelong process augmented by historical perspective, remarkable one-case experiences, and gestalt/gut feeling/intuition. Most of our dermatology resident and medical student teaching has been in the Washington Heights section of Manhattan at Columbia Presbyterian Medical Center; in New Haven, Connecticut, at Yale University School of Medicine; and in New Hyde Park, New York, at Hofstra/ Northwell Donald and Barbara Zucker School of Medicine. We expect that these companion volumes will be helpful in all clinical settings and used by all healthcare providers on the academic campus or in the community environment, anywhere in the world. New York, NY, USA New Haven, CT, USA 

Paul I. Schneiderman Marc E. Grossman

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Contents

The Text

Blaschko-esque Entities��������������������������������������������������������   134

Abdominal Pain, Cutaneous Manifestations���������������������������    1

Blindness, Cutaneous Manifestations�����������������������������������   139

Abscess (Sterile and Non-sterile)�������������������������������������������    4

Blue Lunulae/Blue Nails��������������������������������������������������������   142

Acanthosis Nigricans-Like Lesions�����������������������������������������    11

Blue Sclerae��������������������������������������������������������������������������   143

Acidosis and Rash in the Newborn����������������������������������������   15

Blue Spots�����������������������������������������������������������������������������   143

Acneiform Eruptions���������������������������������������������������������������   15

Blueberry Muffin Lesions, Neonate���������������������������������������   153

Acral Cyanosis�����������������������������������������������������������������������   22

Breast Asymmetry�����������������������������������������������������������������   154

Acral Erythema and Scale With or Without Linear Cutoff�������   27

Breast Cancer, Cutaneous Manifestations����������������������������   154

Acral Erythema�����������������������������������������������������������������������   28

Breast Hypertrophy (Gynecomastia) and Breast Masses�����   155

Acral Papules and Nodules; Knuckle Papules; Papules,

Breast Lesions�����������������������������������������������������������������������   158

Digital���������������������������������������������������������������������������������   32

Buffalo Hump (Cervicodorsal Lipodystrophy)������������������������   161

Acrochordons (Skin Tags)������������������������������������������������������   43

Bullae and/or Vesicles�����������������������������������������������������������   162

Acromegalic Features������������������������������������������������������������   43

Bullae, Hemorrhagic��������������������������������������������������������������   176

Acro-Osteolysis����������������������������������������������������������������������   44

Bullae, Hemorrhagic, Septic��������������������������������������������������   180

Adrenal Disease, Cutaneous Manifestations�������������������������   45

Bullae in Newborn�����������������������������������������������������������������   181

Ainhum�����������������������������������������������������������������������������������   45

Bullae in Infants and Children�����������������������������������������������   183

Alopecia and Structural Abnormalities of the Nose and

Bullae of the Fingers or Toes�������������������������������������������������   187

Hands���������������������������������������������������������������������������������   47

Bullae, Transient, in Infants���������������������������������������������������   190

Alopecia, Eyebrows����������������������������������������������������������������   48

Burning Tongue���������������������������������������������������������������������   190

Alopecia in Neonates, Infants, and Toddlers��������������������������   52

Butterfly Rash������������������������������������������������������������������������   190

Alopecia����������������������������������������������������������������������������������   54

Café au lait macules (CALMs), Associations�������������������������   195

Alveolar Hemorrhage�������������������������������������������������������������   73

Cardiac and/or Cardiovascular Disease and Skin Lesions���   197

Angioedema���������������������������������������������������������������������������   75

CDKN2A with p14 Loss���������������������������������������������������������   205

Angiokeratoma Corporis Diffusum������������������������������������������   76

Cellulitis in the Immunocompromised Host���������������������������   205

Annular Lesions of Penis with Surface Changes�������������������   77

Cellulitis, INFECTIOUS, in the Immunocompetent Host�������   207

Annular Lesions with Surface Changes���������������������������������   77

Cellulitis (Pseudocellulitis), Non-­infectious Etiologies�����������   207

Annular Lesions Without Surface Changes����������������������������   83

Cerebriform Lesions��������������������������������������������������������������   208

Annular Scars�������������������������������������������������������������������������   90

Chalky Material Extruded from Lesions����������������������������������  211

Aortic Disease in the Young���������������������������������������������������   91

Cheilitis (Crusted Lips)�����������������������������������������������������������  211

Aphthous Stomatitis���������������������������������������������������������������   92

Chemotherapy, Cutaneous Manifestations����������������������������   216

Arthritis and Rash (Polyarthritis and Monoarthritis)����������������   94

Chest Wall Tumors����������������������������������������������������������������   219

Aseptic Meningitis, Cutaneous Manifestations����������������������   107

Cleft Lip and/or Palate (Associated SKIN Disorders)������������   219

Atrichia and Nail Abnormalities����������������������������������������������   107

Coarse facies and Coarse Facial Skin����������������������������������   221

Atrophic Glossitis�������������������������������������������������������������������   108

Cobblestone Appearance of Skin������������������������������������������   222

Atrophic Lesions��������������������������������������������������������������������   109

Cobblestone Appearance of the Oral Mucosa�����������������������   227

Autoinflammatory Diseases���������������������������������������������������   126

Cocaine Use, Cutaneous Manifestations������������������������������   230

Bariatric Surgery, Cutaneous Signs of Nutrient Deficiency���   128

Concentric Lesions����������������������������������������������������������������   230

Basal Cell Carcinomas: Syndromes with Basal Cell

Conjunctival Lesions, Pigmented������������������������������������������   231

Carcinomas�����������������������������������������������������������������������   129

Craniosynostosis�������������������������������������������������������������������   231

Bioweapons���������������������������������������������������������������������������   129

Cutaneous Horns������������������������������������������������������������������   231

“Black” Dermatologic Entities������������������������������������������������   130

Cutis Laxa-Like Appearance�������������������������������������������������   233

Black Oral Lesions����������������������������������������������������������������   134

Cutis Verticis Gyrata��������������������������������������������������������������   236 ix

x

CONTENTS

Cysts with or Without Drainage���������������������������������������������   238

Freckling of Hands����������������������������������������������������������������   444

Deafness or Hearing Impairment, Cutaneous Manifestations  243

Gastrointestinal Cancer and Skin Lesions����������������������������   445

Dermatitis (Spongiotic Dermatitis), Differential Diagnosis�����   248

Gastrointestinal Hemorrhage and Skin Lesions��������������������   445

Dermatitis, Facial, Pediatric���������������������������������������������������   258

Gastrointestinal Polyposis and Skin��������������������������������������   446

Dermatitis, Periorbital������������������������������������������������������������   261

Gingival Hyperplasia�������������������������������������������������������������   446

Dermatitis, Periorificial�����������������������������������������������������������   263

Gingivitis��������������������������������������������������������������������������������   450

Dermatographism������������������������������������������������������������������   267

Glomerulonephritis, Cutaneous Manifestations���������������������   454

Desmoplakin Mutations���������������������������������������������������������   268

Granulomas���������������������������������������������������������������������������   455

Diabetes Mellitus, Cutaneous Manifestations�����������������������   268

Granulomatosis with Polyangiitis, Cutaneous Manifestations  456

Diarrhea, Cutaneous Manifestations�������������������������������������   269

Green Pigmentation��������������������������������������������������������������   456

Dimples���������������������������������������������������������������������������������   274

Hair Abnormalities�����������������������������������������������������������������   458

Doughy Skin��������������������������������������������������������������������������   275

Hair Breakage�����������������������������������������������������������������������   459

Drug Abuse, Cutaneous Manifestations��������������������������������   276

Hair Shaft Nodules or Nits (Particulate Matter)���������������������   461

Dyschromatosis (Hypopigmentation and

Hair, Premature Graying��������������������������������������������������������   461

Hyperpigmentation)�����������������������������������������������������������   278

Heart Block and Rash�����������������������������������������������������������   463

Dyshidrosis����������������������������������������������������������������������������   282

Heart Failure, Cutaneous Manifestations������������������������������   464

Ear, Hard (Petrified Auricles)�������������������������������������������������   284

Heliotrope������������������������������������������������������������������������������   465

Ear Lesions���������������������������������������������������������������������������   285

Hematologic Malignancies, Cutaneous Signs�����������������������   466

Ears, Red, with or Without Nodules��������������������������������������   296

Hemihypertrophy (Asymmetric Overgrowth Syndromes)������   467

Edema�����������������������������������������������������������������������������������   299

Herpetiform Lesions��������������������������������������������������������������   469

Edema, Hands�����������������������������������������������������������������������   307

Heterochromia Iridum (IRIDIS)����������������������������������������������   471

Edema, Head�������������������������������������������������������������������������  311

Hoarseness, Cutaneous Manifestations��������������������������������   471

Edema, Legs�������������������������������������������������������������������������   312

Human Papilloma Virus-Associated Immunodeficiency

Erosions (Superficial Ulcers)�������������������������������������������������   317

Syndromes������������������������������������������������������������������������   473

Erythrodermas (Exfoliative Erythroderma)����������������������������   323

Hyperhidrosis������������������������������������������������������������������������   474

Erythrodermic Infant��������������������������������������������������������������   329

Hyperkeratotic Lesions����������������������������������������������������������   479

Eschars���������������������������������������������������������������������������������   332

Hyperkeratotic Lesions of Feet����������������������������������������������   489

Esophageal and Cutaneous Disease������������������������������������   334

Hyperkeratotic Lesions of the Hands������������������������������������   493

Exanthem������������������������������������������������������������������������������   336

Hyperkeratotic Papules of the Nipple������������������������������������   497

Exfoliation (Desquamation)���������������������������������������������������   347

Hyperpigmentation in Blaschko’s Lines���������������������������������   498

Eyelid Lesions�����������������������������������������������������������������������   350

Hyperpigmentation, Diffuse���������������������������������������������������   499

Eyes, Red and Rash�������������������������������������������������������������   363

Hyperpigmentation, Flagellate�����������������������������������������������   503

Facial Asymmetry������������������������������������������������������������������   375

Hyperpigmentation, Paronychial�������������������������������������������   503

Facial Dermatitis, Scaly���������������������������������������������������������   375

Hyperpigmentation, Patchy���������������������������������������������������   504

FACIAL EDEMA���������������������������������������������������������������������   378

Hyperpigmentation, Segmental or Zosteriform����������������������   513

Facial Papules and Plaques��������������������������������������������������   382

Hyperpigmented Lesions, Discrete Annular��������������������������   514

Facial Papules�����������������������������������������������������������������������   385

Hypertrichosis, Generalized��������������������������������������������������   519

Facial Plaques, Scarring and Non-scarring���������������������������   395

Hypertrichosis, Localized������������������������������������������������������   522

Facial Scars���������������������������������������������������������������������������   400

Hypohidrosis (Anhidrosis)�����������������������������������������������������   531

Facial Ulcers��������������������������������������������������������������������������   402

Hypopigmented Patches or Plaques�������������������������������������   537

Facies������������������������������������������������������������������������������������   405

Hypoplasia of Distal Phalanges���������������������������������������������   544

Fetal Akinesia Deformation Sequence����������������������������������   420

Hypotrichosis with Growth and Mental Retardation��������������   545

Fever and Rash, Noninfectious���������������������������������������������   421

Ichthyosiform Eruptions���������������������������������������������������������   546

Fever, Arthritis, and Exanthem����������������������������������������������   423

Immune Deficiency Syndromes with Bacterial Infections������   555

Fibromatoses in Children������������������������������������������������������   427

Inguinal Lymphadenitis and Rash�����������������������������������������   558

Fibrous Tumors, Differential Diagnosis����������������������������������   428

Intertrigo, Including Diaper Dermatitis�����������������������������������   560

Figurate Erythemas���������������������������������������������������������������   428

Iris Lesions, Pigmented���������������������������������������������������������   566

Fingertip Lesions�������������������������������������������������������������������   429

Islands of Sparing������������������������������������������������������������������   566

Fingertip Necrosis�����������������������������������������������������������������   432

Kaposi’s Sarcoma, Differential Diagnosis������������������������������   568

Fingertip Ulcers���������������������������������������������������������������������   434

Kinky Hair������������������������������������������������������������������������������   569

Flushing Disorders����������������������������������������������������������������   436

Knuckle Papules��������������������������������������������������������������������   569

Follicular Plugging�����������������������������������������������������������������   441

Knuckles, Pebbly, with Scarring��������������������������������������������   572

Foot Ulcers����������������������������������������������������������������������������   442

Lacrimal Gland, Enlarged������������������������������������������������������   573

CONTENTS

xi

Lentigines������������������������������������������������������������������������������   573

Nodules, Multilobulated���������������������������������������������������������   717

Leonine Facies����������������������������������������������������������������������   576

Nodules, Multiple, Subcutaneous������������������������������������������   723

Leukoderma, Guttate�������������������������������������������������������������   578

Nodules, Red, Extremities�����������������������������������������������������   727

Leukonychia��������������������������������������������������������������������������   578

Nodules, Red, Face���������������������������������������������������������������   740

Leukoplakia���������������������������������������������������������������������������   580

Nodules, Red, Hand��������������������������������������������������������������   744

Linear Erythronychia�������������������������������������������������������������   583

Nodules, Red or Violaceous, Vascular Appearance��������������   746

Linear Hypopigmentation������������������������������������������������������   583

Nodules, Skin Colored�����������������������������������������������������������   756

Linear Lesions�����������������������������������������������������������������������   584

Nodules, Ulcerated����������������������������������������������������������������   769

Linear Lesions Following Veins���������������������������������������������   596

Nodules, Unspecified Location����������������������������������������������   775

Lip Lesions, Pigmented���������������������������������������������������������   599

Normal Skin (Barely Perceptible Plaque)������������������������������   779

Lip Papules����������������������������������������������������������������������������   600

Obesity Syndromes/Protuberant Abdomen���������������������������   781

Lip Pits�����������������������������������������������������������������������������������   603

Onycholysis���������������������������������������������������������������������������   781

Lipoma Syndromes���������������������������������������������������������������   604

Oral Mucosal Hyperpigmentation������������������������������������������   784

Lips, Swollen�������������������������������������������������������������������������   605

Oral Mucosa, Blue Pigmentation�������������������������������������������   787

Lithium, Cutaneous Side Effects�������������������������������������������   610

Oral Mucosa, Cysts���������������������������������������������������������������   788

Livedo Reticularis with or Without Necrosis��������������������������   610

Oral Mucosa, Nodules�����������������������������������������������������������   789

Liver Disease, Cutaneous Manifestations and Hepatic

Oral Mucosa, Ulceration��������������������������������������������������������   794

Abnormalities of Skin Disease������������������������������������������   617

Oral Mucosa, Verrucous and Vegetating Lesions�����������������   803

Lymphadenopathy for the Dermatologist�������������������������������   622

Osteoma Cutis�����������������������������������������������������������������������   804

Macrocephaly������������������������������������������������������������������������   627

Overgrowth Syndromes���������������������������������������������������������   805

Macrodactyly (Enlarged Digit)�����������������������������������������������   628

P63-Associated Disorders�����������������������������������������������������   807

Malodorous Skin Conditions��������������������������������������������������   633

Painful Tumors����������������������������������������������������������������������   807

Marfanoid Features���������������������������������������������������������������   634

Palatal Necrosis (Necrotic Ulcers of the Palate)�������������������   808

Masses of the Head and Neck����������������������������������������������   635

Palmar and/or Plantar Erythema�������������������������������������������   809

Melanoma, Clinical Simulators����������������������������������������������   639

Palmar and/or Plantar Nodules���������������������������������������������   813

Melanonychia������������������������������������������������������������������������   640

Palmar Pits and Punctate Keratoses/Dyshidrosis-Like

Microcephaly�������������������������������������������������������������������������   642

Lesions������������������������������������������������������������������������������   814

Micronychia and Anonychia���������������������������������������������������   646

Palmoplantar Keratodermas��������������������������������������������������   818

Midline Facial Nodules of Children����������������������������������������   648

Palmoplantar Keratoderma with Atrichia or Hypotrichosis����   831

Midline Nasal Mass���������������������������������������������������������������   648

Papules, Crusted�������������������������������������������������������������������   831

Milia or Milia-Like Lesions (Fine White Papules)�������������������   649

Papules, Digital���������������������������������������������������������������������   836

Monoclonal Gammopathy, Cutaneous Manifestations����������   652

Papules, Dirty Brown�������������������������������������������������������������   841

Mucinoses�����������������������������������������������������������������������������   653

Papules, Distal Digital, White������������������������������������������������   842

Mucocutaneous Candidiasis Syndromes������������������������������   654

Papules, Solitary Facial���������������������������������������������������������   842

Muscle Weakness and Rash�������������������������������������������������   654

Papules, Flat-Topped������������������������������������������������������������   844

Myocarditis, Cutaneous Manifestations���������������������������������   657

Papules, Follicular (Folliculocentric, Including Folliculitis)�����   848

Nail Abnormalities������������������������������������������������������������������   659

Papules, Hyperkeratotic��������������������������������������������������������   857

Nasal Infiltration or Enlargement�������������������������������������������   666

Papules, Hyperpigmented with Hypertrichosis (Hyperpigmented

Nasal Septal Ulcerations/Perforations (Rhinophagic Ulceration)��������������������������������������������������   670

Hairy Papules)������������������������������������������������������������������   864 Papules and Nodules, Hyperpigmented (with or Without

Neck Lesions�������������������������������������������������������������������������   673

Hyperkeratosis)�����������������������������������������������������������������   865

Neck Papules������������������������������������������������������������������������   682

Papules, Periorbital���������������������������������������������������������������   870

Necrosis��������������������������������������������������������������������������������   686

Papules, Red�������������������������������������������������������������������������   872

Neural Tube Dysraphism�������������������������������������������������������   699

Papules, Skin Colored�����������������������������������������������������������   884

Nevi, Associated Syndromes�������������������������������������������������   699

Papulosquamous Eruptions��������������������������������������������������   887

Nipple Dermatitis�������������������������������������������������������������������   702

Paraneoplastic Dermatoses��������������������������������������������������   889

Nipple Lesions, Including Areola with Multiple Papules��������   703

Paraproteinemias, Cutaneous Manifestations�����������������������   892

No Fingerprint Syndromes (Adermatoglyphia, Absent

Parathyroid Disease, Cutaneous Manifestations������������������   893

Dermatoglyphics)��������������������������������������������������������������   708

Paronychia����������������������������������������������������������������������������   894

Nodules, Congenital��������������������������������������������������������������   708

Parotid Gland Enlargement���������������������������������������������������   898

Nodules, Foot������������������������������������������������������������������������   710

Particulate Matter/Exfoliation�������������������������������������������������   901

Nodules, Juxta-Articular��������������������������������������������������������   713

Pedunculated (Polypoid) Lesions������������������������������������������   902

Nodules, Knee�����������������������������������������������������������������������   716

Penile Edema, Acute and Chronic�����������������������������������������   907

xii

CONTENTS

Penile Lesions�����������������������������������������������������������������������   908

Red Chest�����������������������������������������������������������������������������  1061

Penile Ulcers�������������������������������������������������������������������������   916

Red Elbow�����������������������������������������������������������������������������  1062

Perianal Dermatitis and Hypertrophic Plaques����������������������   918

Red Face�������������������������������������������������������������������������������  1063

Perianal Ulcers, Single or Multiple����������������������������������������   922

Red Feet��������������������������������������������������������������������������������  1068

Periorbital Edema/Erythema (Dermatitis)������������������������������   925

Red Nose������������������������������������������������������������������������������  1071

Periorbital Congenital Nodules, Pediatric������������������������������   933

Red Patch������������������������������������������������������������������������������  1074

Periostitis�������������������������������������������������������������������������������   933

Red Plaque����������������������������������������������������������������������������  1085

Peripheral Eosinophilia����������������������������������������������������������   934

Red Scrotum�������������������������������������������������������������������������� 1100

Peripheral Neuropathy, Cutaneous Manifestations���������������   936

Redundant Skin���������������������������������������������������������������������� 1101

Phakomatoses�����������������������������������������������������������������������   939

Renal Failure, Cutaneous Manifestations������������������������������ 1104

Pharyngitis�����������������������������������������������������������������������������   948

Renal Tumor, Cutaneous Manifestations������������������������������� 1109

Photoeruption and Seborrheic Dermatitis-Like Eruption�������   951

Reticulated Eruptions������������������������������������������������������������� 1110

Pigmentary Retinopathy or Cone-Rod Dystrophy with

Reticulated Hyperpigmentation���������������������������������������������� 1116

Dermatologic Manifestations���������������������������������������������   965

Rhinophymatous Eruptions���������������������������������������������������� 1119

Pituitary Disease, Cutaneous Manifestations������������������������   966

Rippling of Skin���������������������������������������������������������������������� 1119

Pityriasis Rosea-Like Eruptions���������������������������������������������   967

Rosette Lesions���������������������������������������������������������������������� 1119

Exogenous Agents����������������������������������������������������������������   968

Saddle Nose Deformity���������������������������������������������������������� 1121

Infections and Infestations�����������������������������������������������������   968

Scalp Cysts���������������������������������������������������������������������������� 1121

Plantar Erythema�������������������������������������������������������������������   969

Scalp Dermatitis��������������������������������������������������������������������� 1123

Pneumonia and Pneumonia-Associated Disease, Cutaneous

Scalp Nodules������������������������������������������������������������������������ 1126

Manifestations�������������������������������������������������������������������   971

Scalp Poliosis������������������������������������������������������������������������� 1135

Poikilodermas of Adulthood���������������������������������������������������   978

Scalp, Red Plaques���������������������������������������������������������������� 1135

Poikilodermas of Childhood���������������������������������������������������   979

Scarring of Neck��������������������������������������������������������������������� 1136

Poliosis, Localized or Generalized (Canities)������������������������   980

Scars, Lesions in Scars���������������������������������������������������������� 1137

Polydactyly (PPD, PAP, and Complex Types)�����������������������   982

Sclerodermoid Changes��������������������������������������������������������� 1140

Pore���������������������������������������������������������������������������������������   983

Scrotal Nodules with Erosions������������������������������������������������ 1147

Port Wine Stain���������������������������������������������������������������������   984

Scrotal Papules and Nodules������������������������������������������������� 1148

Preauricular Sinuses (Ear Pits)���������������������������������������������   985

Scrotal Ulcerations����������������������������������������������������������������� 1150

Pregnancy, Cutaneous Manifestations����������������������������������   986

Serpiginous Lesions��������������������������������������������������������������� 1152

Premature Aging Syndromes (Progeroid Syndromes)����������   987

Short Stature�������������������������������������������������������������������������� 1158

Primary Immunodeficiencies with Granuloma Formation������   989

Sickle Cell Disease, Cutaneous Manifestations��������������������� 1169

Proptosis�������������������������������������������������������������������������������   989

Sinus Tracts���������������������������������������������������������������������������� 1170

Pruritic Tumors����������������������������������������������������������������������   990

Spiky Skin������������������������������������������������������������������������������� 1173

Pruritus, Anal�������������������������������������������������������������������������   991

Spinal Dysraphism (Cutaneous Stigmata)����������������������������� 1173

Pruritus, Erythematous Papules��������������������������������������������   992

Splinter Hemorrhages������������������������������������������������������������ 1174

Pruritus, Generalized, Without Primary Skin Lesions������������   994

Sporotrichoid Lesions������������������������������������������������������������� 1174

Pruritus, Vulvar����������������������������������������������������������������������   998

Spotty Pigmentation of the Face�������������������������������������������� 1176

Pseudoxanthoma Elasticum-Like Changes���������������������������   999

Striae Distensae (Stretch Marks)������������������������������������������� 1176

Psoriasiform Dermatitis���������������������������������������������������������  1000

Stroke Syndromes, Cutaneous Manifestations���������������������� 1177

Psoriasiform Plaque, Focal or Solitary����������������������������������  1006

Swollen Calf��������������������������������������������������������������������������� 1178

Pterygium (Webbing)�������������������������������������������������������������  1008

Syndactyly������������������������������������������������������������������������������ 1179

Pterygium of the Nail�������������������������������������������������������������  1008

Synophrys������������������������������������������������������������������������������ 1183

Puberty, Delayed (Hypogonadism)����������������������������������������  1010

Tails���������������������������������������������������������������������������������������� 1184

Puberty, Premature����������������������������������������������������������������  1013

Tall Stature Syndromes���������������������������������������������������������� 1184

Pulmonary Disease Associated with Skin Disease���������������  1015

Target Lesions������������������������������������������������������������������������ 1184

Pulsatile Papules�������������������������������������������������������������������  1021

Tattoo, Palpable/Lesions in a Tattoo��������������������������������������� 1189

Punctate and Reticulate Hyperpigmentation�������������������������  1021

Teeth��������������������������������������������������������������������������������������� 1191

Purpura����������������������������������������������������������������������������������  1023

Telangiectasias����������������������������������������������������������������������� 1199

Purpura, Neonatal�����������������������������������������������������������������  1040

Testicular Enlargement����������������������������������������������������������  1206

Purpuric Rash and Fever������������������������������������������������������  1041

Thumbs���������������������������������������������������������������������������������  1207

Pustular and Vesicopustular Eruptions in the Newborn��������  1046

Thyroid Disease, Cutaneous Manifestations�������������������������  1207

Pustules and Pustular Eruptions of the Palms and Soles�����  1048

Tongue, Enlarged (Macroglossia)������������������������������������������  1209

Pustules and Pustular Eruptions�������������������������������������������  1049

Tongue, Hyperpigmentation��������������������������������������������������  1213

CONTENTS

xiii

Tongue, Multilobulated����������������������������������������������������������  1214

Acral Erythema����������������������������������������������������������������������  1374

Tongue Necrosis (Lingual Necrosis)��������������������������������������  1216

Acral Erythema and Scale�����������������������������������������������������  1377

Tongue Nodules, Solitary������������������������������������������������������  1216

Acral Necrosis�����������������������������������������������������������������������  1379

Tongue, Red��������������������������������������������������������������������������  1217

Acral Nodules������������������������������������������������������������������������  1380

Tongue, Scrotal (Plicated Tongue, Fissured Tongue)������������  1219

Acral Papules������������������������������������������������������������������������  1383

Tongue, Ulcers����������������������������������������������������������������������  1220

Acral Papules and Nodules���������������������������������������������������  1396

Trichomegaly�������������������������������������������������������������������������  1222

Acral Pits�������������������������������������������������������������������������������  1397

Tropical Fever And Rash�������������������������������������������������������  1224

Acromegalic Features�����������������������������������������������������������  1397

Tumors, Giant������������������������������������������������������������������������  1227

Ainhum����������������������������������������������������������������������������������  1398

Ulcers, Leg����������������������������������������������������������������������������  1233

Alopecia���������������������������������������������������������������������������������  1400

Ulcers, Leg, in a Young Patient���������������������������������������������  1239

Alopecia of the Eyebrows������������������������������������������������������  1410

Ulcers������������������������������������������������������������������������������������  1242

Angioedema��������������������������������������������������������������������������� 1411

Umbilical Lesions������������������������������������������������������������������  1255

Annular Lesions of the Penis�������������������������������������������������� 1411

Umbilical Nodules������������������������������������������������������������������  1259

Annular Lesions with Scars���������������������������������������������������  1412

Umbilicated Lesions��������������������������������������������������������������  1261

Annular Lesions with Surface Change����������������������������������  1412

Unilateral Foot Edema�����������������������������������������������������������  1265

Annular Lesions Without Surface Change����������������������������  1423

Urticaria and Urticaria-Like Lesions��������������������������������������  1265

Aphthae���������������������������������������������������������������������������������  1431

Uveitis, Cutaneous Manifestations����������������������������������������  1273

Arthritis and Rash������������������������������������������������������������������  1433

Uvula, Enlarged���������������������������������������������������������������������  1275

Atrophic Glossitis�������������������������������������������������������������������  1440

Valvular Heart Disease, Cutaneous Manifestations��������������  1277

Atrophy����������������������������������������������������������������������������������  1442

Vasculitis, Granulomatous�����������������������������������������������������  1278

Black Lesions������������������������������������������������������������������������  1452

Vasculitis, Leukocytoclastic���������������������������������������������������  1278

Blaschko-Esque Entities��������������������������������������������������������  1458

Vasculitis, Thrombotic������������������������������������������������������������  1280

Blue Spots�����������������������������������������������������������������������������  1465

Vasculitis, Types��������������������������������������������������������������������  1281

Blueberry Muffin Lesions, Neonate���������������������������������������  1477

Vegetating Lesions����������������������������������������������������������������  1282

Breast Asymmetry�����������������������������������������������������������������  1477

Verrucous Lesions of the Legs����������������������������������������������  1284

Breast Lesions�����������������������������������������������������������������������  1478

Verrucous Lesions, Periungual����������������������������������������������  1285

Bullae������������������������������������������������������������������������������������  1485

Verrucous Plaques����������������������������������������������������������������  1286

Bullae in Children������������������������������������������������������������������  1498

Vulva, Hypertrophic, and/or Edematous Lesions������������������  1293

Bullae in Children, Acral��������������������������������������������������������  1498

Vulvar Edema������������������������������������������������������������������������  1296

Bullae, Fingers and Toes�������������������������������������������������������  1499

Vulvar Erythema With or Without Pruritus�����������������������������  1297

Bullae, Giant��������������������������������������������������������������������������  1502

Vulvar Papules and Nodules�������������������������������������������������  1299

Bullae, Hemorrhagic��������������������������������������������������������������  1508

Vulvar Ulcers�������������������������������������������������������������������������  1303

Bullae, Hemorrhagic Septic���������������������������������������������������  1514

White Feet�����������������������������������������������������������������������������  1307

Bullae, Neonatal��������������������������������������������������������������������  1518

White Macules�����������������������������������������������������������������������  1307

Butterfly Rash������������������������������������������������������������������������  1518

White Papules, Nodules, and Plaques����������������������������������  1314

Cafe au lait macules, Associations����������������������������������������  1530

Woolly Hair����������������������������������������������������������������������������  1318

Cellulitis-Like Lesions������������������������������������������������������������  1530

Xanthomatous Lesions����������������������������������������������������������  1320

Cerebriform Lesions��������������������������������������������������������������  1532

Xerosis, Associations and Causes����������������������������������������  1320

Cheilitis, Including Swollen Lips��������������������������������������������  1534

Yellow Nails���������������������������������������������������������������������������  1325

Clitoromegaly������������������������������������������������������������������������  1544

Yellow or Skin-Colored Papules of the Neck�������������������������  1325

Clubbing��������������������������������������������������������������������������������  1545

Yellow Papules and Plaques�������������������������������������������������  1327

Cobblestoned Oral Mucosa���������������������������������������������������  1546

Yellow Plaque������������������������������������������������������������������������  1332

Cobblestoned Skin����������������������������������������������������������������  1548

Yellow Skin (Xanthoderma)���������������������������������������������������  1334

Cocaine Abuse����������������������������������������������������������������������  1561

Zebra Stripes�������������������������������������������������������������������������  1337

Columbia Presbyterian Medical Center���������������������������������  1563

Zosteriform Lesions/Segmental Disorders����������������������������  1340

Concentric Lesions����������������������������������������������������������������  1563 Conjunctivae, Hyperpigmented���������������������������������������������  1564

The Atlas

Conjunctivae, Red�����������������������������������������������������������������  1565

Abscess���������������������������������������������������������������������������������  1346

Covid-19 Rashes�������������������������������������������������������������������  1567

Acanthosis Nigricans-Like Lesions����������������������������������������  1353

Crix Belly�������������������������������������������������������������������������������  1569

Acneiform Lesions�����������������������������������������������������������������  1355

Cushingoid Appearance��������������������������������������������������������  1569

Acral Bullae���������������������������������������������������������������������������  1368

Cutaneous Horn��������������������������������������������������������������������  1570

Acral Cyanosis����������������������������������������������������������������������  1369

Cutis Laxa-Like Appearance�������������������������������������������������  1572

xiv

CONTENTS

Cysts��������������������������������������������������������������������������������������  1574

Hair Nodules (Particulate Matter)������������������������������������������� 1811

Dermatitis������������������������������������������������������������������������������  1578

Hair, Unruly����������������������������������������������������������������������������� 1811

Dermatitis of Hands or Feet��������������������������������������������������  1586

Hemihypertrophy�������������������������������������������������������������������  1813

Dermatitis of the Palms���������������������������������������������������������  1589

Herpetiform Lesions��������������������������������������������������������������  1814

Dermatitis, Facial, Adult���������������������������������������������������������  1591

Hyperelastic Skin�������������������������������������������������������������������  1817

Dermatitis, Facial, Pediatric���������������������������������������������������  1600

Hyperkeratotic Lesions����������������������������������������������������������  1818

Dermatitis, Fingertips������������������������������������������������������������  1604

Hyperkeratotic Lesions of Feet����������������������������������������������  1827

Dermatitis, Perianal���������������������������������������������������������������  1605

Hyperkeratotic Lesions of Hands������������������������������������������  1830

Dermatitis, Periorificial, Adult�������������������������������������������������  1605

Hyperpigmentation, Discrete Annular������������������������������������  1832

Dermatitis, Periorificial, Pediatric�������������������������������������������  1609

Hyperpigmentation, Generalized�������������������������������������������  1838

Desquamatian (Exfoliation)���������������������������������������������������  1610

Hyperpigmentation, Patchy���������������������������������������������������  1844

Dimples���������������������������������������������������������������������������������  1615

Hyperpigmented Plaques������������������������������������������������������  1848

Dyschromatosis���������������������������������������������������������������������  1617

Hypertrichosis, Generalized��������������������������������������������������  1850

Dyshidrosiform Lesions���������������������������������������������������������  1620

Hypertrichosis, Localized������������������������������������������������������  1850

Ear Lesions���������������������������������������������������������������������������  1625

Hypopigmented Papules�������������������������������������������������������  1854

Ear, Hard�������������������������������������������������������������������������������  1633

Hypopigmented Patches�������������������������������������������������������  1855

Ear, Red��������������������������������������������������������������������������������  1635

Ichthyosiform Eruptions���������������������������������������������������������  1859

Ear, Swollen��������������������������������������������������������������������������  1637

Intertrigo��������������������������������������������������������������������������������  1870

Edema�����������������������������������������������������������������������������������  1638

Iris lesions, Pigmented����������������������������������������������������������  1880

Edema of Fingers or Toes�����������������������������������������������������  1641

Islands of Sparing������������������������������������������������������������������  1881

Edema of the Foot�����������������������������������������������������������������  1644

Knee Lesions�������������������������������������������������������������������������  1884

Edema of the Hands��������������������������������������������������������������  1647

Knuckle Papules��������������������������������������������������������������������  1884

Edema of the Legs����������������������������������������������������������������  1652

Koilonychia����������������������������������������������������������������������������  1890

Elbow Plaques�����������������������������������������������������������������������  1655

Lacrimal Gland Enlargement�������������������������������������������������  1891

Enanthem������������������������������������������������������������������������������  1656

Lentigines������������������������������������������������������������������������������  1892

Erosions��������������������������������������������������������������������������������  1657

Leonine Facies����������������������������������������������������������������������  1895

Erythroderma�������������������������������������������������������������������������  1668

Leukonychia��������������������������������������������������������������������������  1897

Erythroderma in Infancy��������������������������������������������������������  1679

Leukoplakia���������������������������������������������������������������������������  1899

Eschar�����������������������������������������������������������������������������������  1681

Linear Lesions�����������������������������������������������������������������������  1903

Exanthem������������������������������������������������������������������������������  1683

Linear Lesions Over Veins or Lymphatics�����������������������������  1913

Exophthalmos������������������������������������������������������������������������  1699

Lip Lesions����������������������������������������������������������������������������  1918

Eyelid Lesions�����������������������������������������������������������������������  1700

Lip Papules����������������������������������������������������������������������������  1919

Eyes, Red������������������������������������������������������������������������������  1710

Lip Pigmentation��������������������������������������������������������������������  1921

Facial Asymmetry������������������������������������������������������������������  1717

Lip Ulcer��������������������������������������������������������������������������������  1922

Facial Edema������������������������������������������������������������������������  1722

Livedo Reticularis With or Without Necrosis�������������������������  1923

Facial Papules�����������������������������������������������������������������������  1734

Lymphadenopathy�����������������������������������������������������������������  1933

Facial Papules and Plaques��������������������������������������������������  1743

Macrocephaly������������������������������������������������������������������������  1936

Facial Plaques�����������������������������������������������������������������������  1747

Macrodactyly�������������������������������������������������������������������������  1937

Facial Scars���������������������������������������������������������������������������  1755

Macromano���������������������������������������������������������������������������  1939

Facial Ulcer���������������������������������������������������������������������������  1758

Marfanoid Features���������������������������������������������������������������  1940

Facies������������������������������������������������������������������������������������  1764

Melanoma Mimickers������������������������������������������������������������  1943

Fever and Rash���������������������������������������������������������������������  1784

Melanonychia������������������������������������������������������������������������  1943

Filiform Lesions���������������������������������������������������������������������  1785

Micronychia and Anonychia���������������������������������������������������  1944

Fingertip Lesions�������������������������������������������������������������������  1785

Milia���������������������������������������������������������������������������������������  1947

Fingertip or Toetip Necrosis���������������������������������������������������  1790

Mountain Range Lesions�������������������������������������������������������  1949

Fingertip or Toetip Ulcer��������������������������������������������������������  1795

Nails��������������������������������������������������������������������������������������  1956

Fissures���������������������������������������������������������������������������������  1797

Nails, Hyperkeratotic�������������������������������������������������������������  1964

Flagellate�������������������������������������������������������������������������������  1797

Nasal Destruction, Septal Perforation, or Ulcerations�����������  1967

Flushing���������������������������������������������������������������������������������  1798

Nasal Infiltration and/or Enlargement������������������������������������  1968

Foot Ulcers����������������������������������������������������������������������������  1804

Neck Lesions�������������������������������������������������������������������������  1970

Gingival Hyperplasia�������������������������������������������������������������  1805

Neck Papules������������������������������������������������������������������������  1979

Gingivitis��������������������������������������������������������������������������������  1806

Necrosis��������������������������������������������������������������������������������  1981

Green Skin����������������������������������������������������������������������������  1808

Nevi���������������������������������������������������������������������������������������  1999

CONTENTS

xv

Nipple Dermatitis�������������������������������������������������������������������  1999

Pityriasis Rosea-Like�������������������������������������������������������������  2167

Nipple Lesions�����������������������������������������������������������������������  2000

Plantar Nodules���������������������������������������������������������������������  2171

Nodules of the Elbows�����������������������������������������������������������  2004

Poikilodermas, Childhood and Adulthood������������������������������  2172

Nodules of the Foot���������������������������������������������������������������  2004

Pore���������������������������������������������������������������������������������������  2173

Nodules of the Hands������������������������������������������������������������  2006

Pruritus Without Rash�����������������������������������������������������������  2174

Nodules of the Knee��������������������������������������������������������������  2007

Pseudoxanthoma Elasticum-Like Changes���������������������������  2177

Nodules, Juxtaarticular����������������������������������������������������������  2007

Psoriasiform Dermatitis���������������������������������������������������������  2179

Nodules, Multilobulated���������������������������������������������������������  2010

Psoriasiform Plaque, Solitary or Localized����������������������������  2190

Nodules, Multiple Subcutaneous�������������������������������������������  2017

Pterygium of the Nails�����������������������������������������������������������  2194

Nodules, Purple Plum������������������������������������������������������������  2018

Pterygium Unguis Inversum��������������������������������������������������  2195

Nodules, Red�������������������������������������������������������������������������  2020

Purpura����������������������������������������������������������������������������������  2195

Nodules, Red, of the Extremities�������������������������������������������  2021

Purpura in the Neonate���������������������������������������������������������  2209

Nodules, Red, of the Face�����������������������������������������������������  2032

Purpura of the Face���������������������������������������������������������������  2210

Nodules, Red, of the Hand����������������������������������������������������  2037

Purpura with Fever����������������������������������������������������������������� 2211

Nodules, Skin Colored�����������������������������������������������������������  2038

Pustular Eruptions�����������������������������������������������������������������  2216

Nodules, Ulcerated����������������������������������������������������������������  2044

Pustular Eruptions of Infancy������������������������������������������������  2225

Nodules, Vascular Appearance���������������������������������������������  2052

Pustular Eruptions of the Face����������������������������������������������  2226

Normal Skin (Barely Perceptible Lesions)�����������������������������  2058

Pustular Eruptions of the Neonate����������������������������������������  2228

Onycholysis���������������������������������������������������������������������������  2060

Pustular Eruptions of the Palms and Soles���������������������������  2229

Oral Mucosa, Red Plaques���������������������������������������������������  2061

Red Elbow�����������������������������������������������������������������������������  2232

Oral Mucosa, Ulceration��������������������������������������������������������  2062

Red Face�������������������������������������������������������������������������������  2234

Oral Mucosal Pigmentation���������������������������������������������������  2065

Red Feet��������������������������������������������������������������������������������  2255

Oral Nodules�������������������������������������������������������������������������  2066

Red Hand������������������������������������������������������������������������������  2259

Oral Vegetative Lesions��������������������������������������������������������  2068

Red Knee������������������������������������������������������������������������������  2260

Palmar and/or Plantar Pits and Punctate Keratoses�������������  2069

Red Leg���������������������������������������������������������������������������������  2260

Palmar Erythema�������������������������������������������������������������������  2071

Red Lunula����������������������������������������������������������������������������  2261

Palmoplantar Keratoderma���������������������������������������������������  2074

Red Nose������������������������������������������������������������������������������  2261

Papules and Nodules, Hyperpigmented��������������������������������  2081

Red Patch������������������������������������������������������������������������������  2263

Papules, Crusted�������������������������������������������������������������������  2085

Red Plaque����������������������������������������������������������������������������  2269

Papules, Dirty Brown�������������������������������������������������������������  2089

Red scrotum��������������������������������������������������������������������������  2281

Papules, Flat-Topped������������������������������������������������������������  2089

Redundant Skin���������������������������������������������������������������������  2283

Papules, Follicular�����������������������������������������������������������������  2092

Reticulated����������������������������������������������������������������������������  2284

Papules, Hyperkeratotic��������������������������������������������������������  2101

Reticulated Hyperpigmentation���������������������������������������������  2288

Papules, Red�������������������������������������������������������������������������  2104

Rosette Lesions���������������������������������������������������������������������  2290

Papulosquamous Eruptions��������������������������������������������������� 2114

Scalp Dermatitis��������������������������������������������������������������������  2292

Papulovesicles����������������������������������������������������������������������� 2119

Scalp Nodules�����������������������������������������������������������������������  2297

Paraneoplastic Disorders������������������������������������������������������� 2119

Scalp Ulcers��������������������������������������������������������������������������  2302

Paronychia����������������������������������������������������������������������������  2120

Scalp, Red Plaques���������������������������������������������������������������  2305

Parotid Gland Enlargement���������������������������������������������������  2123

Scars, Lesions in Scars���������������������������������������������������������  2306

Particulate Matter������������������������������������������������������������������  2124

Sclerodermoid Changes��������������������������������������������������������  2315

Peau d’orange�����������������������������������������������������������������������  2125

Scrotal Edema�����������������������������������������������������������������������  2320

Pebbly Skin���������������������������������������������������������������������������  2128

Scrotal Papules and Nodules������������������������������������������������  2321

Pedunculated Lesions�����������������������������������������������������������  2128

Scrotal Ulcers������������������������������������������������������������������������  2323

Penile Lesions�����������������������������������������������������������������������  2130

Serpiginous Lesions��������������������������������������������������������������  2325

Penile Ulcers�������������������������������������������������������������������������  2137

Short Stature�������������������������������������������������������������������������  2334

Perianal Ulcers, Single or Multiple����������������������������������������  2138

Sinus Tracts���������������������������������������������������������������������������  2335

Perianal Dermatitis����������������������������������������������������������������  2140

Sporotrichoid Pattern�������������������������������������������������������������  2338

Perianal Nodules�������������������������������������������������������������������  2144

Stellate Lesions���������������������������������������������������������������������  2340

Periarticular Erythema�����������������������������������������������������������  2144

Strange But True�������������������������������������������������������������������  2341

Perifollicular Erythema����������������������������������������������������������  2145

Striae�������������������������������������������������������������������������������������  2342

Periorbital Edema, Erythema������������������������������������������������  2145

Syndactyly�����������������������������������������������������������������������������  2343

Periorbital Papules����������������������������������������������������������������  2151

Targetoid Lesions������������������������������������������������������������������  2345

Photodermatitis – Seborrheic Dermatitis�������������������������������  2152

Tattoos�����������������������������������������������������������������������������������  2350

xvi

CONTENTS

Tattoos, Concentration Camp������������������������������������������������  2354

Uvula�������������������������������������������������������������������������������������  2414

Teeth, Abnormalities��������������������������������������������������������������  2355

Vegetative Plaques����������������������������������������������������������������  2415

Telangiectasias����������������������������������������������������������������������  2358

Verrucous Plaques����������������������������������������������������������������  2417

Tongue Hyperpigmentation���������������������������������������������������  2362

Vulvar Edema������������������������������������������������������������������������  2424

Tongue Lesions���������������������������������������������������������������������  2362

Vulvar Erythema��������������������������������������������������������������������  2425

Tongue Papules���������������������������������������������������������������������  2363

Vulvar Hyperpigmentation�����������������������������������������������������  2426

Tongue Ulcers�����������������������������������������������������������������������  2365

Vulvar Hypertrophic Lesions��������������������������������������������������  2426

Tongue, Enlarged (Macroglossia)������������������������������������������  2370

Vulvar Hypertrophic Plaques�������������������������������������������������  2426

Tongue, Multilobulated����������������������������������������������������������  2371

Vulvar Papules and Nodules�������������������������������������������������  2428

Tongue, Red��������������������������������������������������������������������������  2372

Vulvar Ulcers�������������������������������������������������������������������������  2428

Trichomegaly�������������������������������������������������������������������������  2374

Wallace’s Line�����������������������������������������������������������������������  2432

Tumors, Giant������������������������������������������������������������������������  2374

White Macules or Patches�����������������������������������������������������  2433

Ulcers������������������������������������������������������������������������������������  2381

White Papules, Nodules, or Plaques�������������������������������������  2440

Ulcers of the foot�������������������������������������������������������������������  2386

Xerosis����������������������������������������������������������������������������������  2449

Ulcers of the hand�����������������������������������������������������������������  2390

Yellow Papules and Nodules�������������������������������������������������  2452

Ulcers of the Leg�������������������������������������������������������������������  2391

Yellow Skin����������������������������������������������������������������������������  2456

Umbilical lesions��������������������������������������������������������������������  2399

Zebra Stripes�������������������������������������������������������������������������  2459

Umbilicated lesions���������������������������������������������������������������  2402

Zosteriform Eruptions������������������������������������������������������������  2465

Urticaria and Urticarial-Like Lesions��������������������������������������  2408

Index���������������������������������������������������������������������������������������� 2475

 BDOMINAL PAIN, CUTANEOUS A MANIFESTATIONS

40:447–454, 2011; abdominal venous thrombosis BMJ Case Rep June 29, 2011; cytomegalovirus infection Int J Surg Case Rep 23:7073, 2016 Adult onset Still’s disease Medicine (Balt)96:e6318, 2017

 UTOIMMUNE DISORDERS AND DISORDERS A OF IMMUNE DYSREGULATION

DEVELOPMENTAL ANOMALIES

Acute graft vs. host disease

Horseshoe kidneys- flushing, nausea, abdominal pain (Rovsing’s syndrome) JAAD 55:1075–1077, 2006; JAAD 55:193–208, 2006

Anaphylaxis – flushing, urticaria, angioedema; hypotension, upper airway edema, pulmonary symptoms, abdominal pain, rhinitis, headaches, substernal chest pain JAAD 55:193–208, 2006

Omphalomesenteric duct (connects yolk sac to midgut) remnants cutaneous remnants of the omphalomesenteric duct - completely patent duct – red nodule (raspberry tumor) with a fistula with fecal discharge or intestinal prolapse; melena, anemia, abdominal pain, intussusception, intestinal obstruction JAAD 72:1066–1073, 2015; Am J Surg 88:829–834, 1954

Angioedema JAAD 25:155–161, 1991 Chronic granulomatous disease – hepatic abscesses Case Rep Gastroenterol 6:20–25, 2012; J Intern Med 228:409–410, 1990; Digestion 39:1–6, 1988 Dermatitis herpetiformis – dapsone-induced pancreatitis Ann Pharmacother 37:1438–1440, 2003 Dermatomyositis – gastrointestinal carcinoma; colonic vasculopathy and perforation BMJ Case Rep Jan 12, 2016; small bowel perforation Int J Surg Case Rep 65:245–248, 2019

DRUG-INDUCED Dimethyl fumarate – treatment for multiple sclerosis J Drugs in Dermatol 13:1144–1147, 2014

Familial cold autoinflammatory syndrome (cold urticaria) – autosomal dominant; non-pruritic urticarial (papules and plaques) rash precipitated by cold lasting 12 hours; ocular pain, conjunctivitis, blurred vision, arthralgias of knees and ankles and arthritis; fever and rash more severe in evening; abdominal pain, headache, nausea, sweating, drowsiness, extreme thirst, mutation in gene encoding NALP3 (cryopyrin); CIAS1 JAAD 68:834–853, 2013; AD 144:392–402, 2008; Ped Derm 24:85–89, 2007; AD 142:1591– 1597, 2006; JAAD 54:319–321, 2006; BJD 150:1029–1031, 2004; JAMA 114:1067–1068, 1940

EXOGENOUS AGENTS Marijuana - hyperemesis syndrome – periods of nausea, vomiting, abdominal pain; compulsive bathing Clin Inf Dis 61:1840–1849, 2015 Scombroid fish poisoning – abdominal pain, flushing JAAD 77:391–402, 2017 Sulfites – cured meats; flushing JAAD 55:193–208, 2006

Hereditary angioedema – autosomal dominant; C’1 INH deficiency NEJM 359:1027–1036, 2008; J Allergy Clin Immunol 106:546–550, 2000; Lancet 356:213–217, 2000; NEJM 334:1666–1667, 1996; JAAD 53:373–388, 2005; BJD 150:157–158, 2004; Eur J Gastroenterol Hepatol 24:353–361, 2012; type III in men and women BJD 154:542–545, 2006; serpiginous erythema; triad of circumscribed edema of the skin, laryngeal edema, and abdominal pain Case Rep Hematol Jan 19, 2018; BJD 161:1153–1158, 2009; Hosp TID No.40.1 rk 4:741–747, 1886; Monatsschr Prakt Dermatol 1:129–131, 1882

INFECTIOUS DISEASES Acanthamoeba Clin Inf Dis 27:1547–1548, 1998; Clin Inf Dis 20:1207–1216, 1995 Anaplasmosis (Anaplasm phagocytophilum) (human granulocytic anaplasmosis) – acute pancreatitis MMWR 65:1–44, May 23, 2016 Anthrax – due to heroin skin popping; edema, necrosis, blistering, compartment syndrome, necrotizing fasciitis; abdominal pain, nausea, vomiting; meningitis, intracranial hemorrhage Clin Inf Dis 61:1840–1849, 2015; Lancet 356:1574–1575, 2000

Hyper IgD syndrome - autosomal recessive; morbilliform eruptions, red macules or papules, urticaria, red nodules, combinations of recurrent periodic fever, no arthritis, rather arthralgias, and rash, annular erythema, and pustules, abdominal pain with vomiting and diarrhea, oral and vaginal aphthae; splenomegaly, cervical lymphadenopathy; elevated IgD and IgA - mevalonate kinase deficiency (MVK); seen in Dutch Ped Derm 35:482–485, 2018; JAAD 68:834–853, 2013; AD 144:392–402, 2008; Ped Derm 22:138–141, 2005; AD 136:1487–1494, 2000; AD 130:59–65, 1994; Medicine 73:133–144, 1994; Lancet 1:1084–1090, 1984

Ascariasis – unilateral eyelid edema Klin Oczna 97:346–347, 1995 (Polish) Brazilian spotted fever (Rickettsii) An Bras Dermatol 90:248–250, 2015 Brucellosis Infez Med 22:326–330, 2014 Chagas’ disease – megacolon, intestinal perforation; unilateral painful bipalpebral edema, conjunctivitis, local lymphadenopathy, periorbital cellulitis, furuncular lesions (chagomas), panniculitis, cardiac involvement JAAD 75:19–30, 2016

Leukocyte adhesion deficiency(beta-2 integrin deficiency) – peritonitis, abscesses, cellulitis, skin ulcerations, pyoderma gangrenosum; ulcerative stomatitis BJD 139:1064–1067, 1998; J Pediatr 119:343– 354, 1991; Ann Rev Med 38: 175–194, 1987; J Infect Dis 152:668– 689, 1985; congenital deficiency of leucocyte-adherence glycoproteins (CD11a (LFA-1), CD11b, CD11c, CD18) – necrotic cutaneous abscesses, psoriasiform dermatitis, gingivitis, periodontitis, septicemia, ulcerative stomatitis, pharyngitis, otitis, pneumonia J Clin Immunol 34:788–791, 2014; Hematol Oncol Clin NA 27:101– 116, 2013; BJD 123:395–401, 1990

Cysticercosis (Taenia solium)(Cysticercus cellulosae) – undercooked pork; multiple asymptomatic subcutaneous nodules; multiple red painless nodules of legs; abdominal pain, muscle edema and pain; diarrhea; neurocysticercosis JAAD 73:929–944, 2015; JAAD 43:538–540, 2000; JAAD 25:409–414, 1991; NEJM 330:1887, 1994; JAAD 12:304–307, 1985 Cytomegalovirus infection – abdominal pain and diarrhea; ulceration of GI tract may lead to hemorrhage and/or perforation

Systemic lupus erythematosus – vasculitis and abdominal pain Lupus 23:1426–1429, 2014; J Rheumatol 40:2015–2022, 2013; lupus enteritis Am J Med 132:e557–558, 2019; Semin Arthr Rheum

Dengue fever (Flavivirus) – palmar erythema and edema; morbilliform or scarlatiniform eruption (classic dengue fever) – initially (first

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

24 hours) flushing of face, neck, and chest; morbilliform or macular erythema with white islands of sparing and petechiae (“white islands in a sea of red”) Clin Inf Dis 36:1004–1005,1074–1075, 2003; acral and/or periorbital edema, petechial mucosae, headache, fever, retroorbital pain, arthralgia, myalgia, leukopenia; absence of sore throat and cough; conjunctival hemorrhages, abdominal pain; platelet count under 240,000; incubation period 3–14 days; Aedes aegypti/A. albopictus Dermatol Clinics 29:33–38, 2011; Am J trop Med Hyg 82:922, 2010; JAAD 58:308–316, 2008; JAAD 46:430– 433, 2002; Dermatol Clinics 17:29–40, 1999; Inf Dis Clin NA 8:107, 1994; Ebola virus hemorrhagic fever (Filovirus) – morbilliform exanthem which becomes purpuric with desquamation of palms and soles; high fever, body aches, myalgia, arthralgias, prostration, abdominal pain, watery diarrhea; disseminated intravascular coagulation Int J Dermatol 51:1037–1043, 2012; JAMA 287:2391–2002; Int J Dermatol 51:1037–1043, 2012; JAAD 65:1213–1218, 2011; MMWR 44, No.19, 382, 1995 Ehrlichia chaffeensis (human monocytic ehrlichiosis) – fever, headache, malaise, myalgia; nausea, vomiting, diarrhea, abdominal pain; 1/3 with petechial or morbilliform eruption or diffuse erythema MMWR 65:1–44, May 23, 2016; Clin Inf Dis 34:1206–1212, 2002; J Clin Gastroenterol 25:544–545, 1997 Fasciola hepatica Clin Microbiol Infect 18:91–96, 2012 Gnathostomiasis – intermittent migratory swellings and nodules; subcutaneous hemorrhages along tracks of migration; urticarial, abdominal pain, nausea and vomiting, diarrhea; South East Asia JAAD 73:929–944, 2015 Herpes zoster Ped Inf Dis 2008.PMID.18277922Tohoku J Exp Med 2001.PMID.11780725 Lassa fever – capillary leak syndrome with severe swelling of head and neck, oral ulcers, tonsillar patches JAAD 65:1213–1218, 2011 Melioidosis (Burkholderia pseudomallei) – abscesses, abdominal pain, nausea, vomiting, necrotizing pneumonia Clin Inf Dis 60:243—250, 2015 Meningococcemia Mumps - orchitis, meningitis, pancreatitis in post-vaccine era Medicine (Balt)89:96–116, 2010 Mycobacterium tuberculosis – abdominal pain, rash, and lymphadenopathy; papulonecrotic tuberculid NEJM 380:275–283, 2019 Parechovirus type 3 – young infants; high fever, poor perfusion, irritability; sepsis-like presentation; erythrodermic rash, abdominal distension, edema, hepatitis; recovery common Clin Inf Dis 60:228–236, 2015 Rocky Mountain spotted fever – acute abdominal pain mimicking appendicitis Am J Dis Child 140:742–744, 1986; mimicking acute cholecystitis Arch Int Med 145:2194–2196, 1985 Salmonella – erythema nodosum Case Rep Gastroenterol 13:456–461, 2019 Scrub typhus (Orientia (Rickettsia) tsutsugamushi)(larval stage of trombiculid mites (chiggers)) – headache and conjunctivitis; eschar with black crust (“cigarette burn-like: eschar); generalized macular or morbilliform rash; jaundice and abdominal pain Clin Inf Dis 60:1828,1864–1865, 2015; Clin Inf Dis 39:1329–1335, 2004; AD 139:1545–1552, 2003; JAAD 2:359–373, 1980; eschar and ulceration JAAD 47:766–769, 2002 Severe fever with thrombocytopenia (SFTS bunyavirus) – fever, nausea and vomiting, abdominal pain, myalgia, lymphadenopathy, confusion, headache, conjunctival congestion, and cough NEJM 364:1523–1532, 2011

Strongyloidiasis hyperinfection (Strongyloides stercoralis) NEJM 371:1051–1060, 2014; Clin Inf Dis 59:559,601–602, 2014; SKINMed 9:199–202, 2011; Semin Arthr Rheum 36:135–143, 2006 Syphilis, secondary Trichinosis – initially have abdominal pain and diarrhea Clin Inf Dis 59:1750–1756, 2014 Tuberculosis – sinus tracts; abdominal tuberculosis – fever, weight loss, abdominal pain and doughy abdomen Scand J Gastroenterol 36:528–532, 2001 Tularemia – Francisella tularensis (non-encapsulated gram-negative coccobacillus); transmitted in tick feces; skin, eye, respiratory, gastrointestinal portals of entry; ulceroglandular, oculoglandular, glandular types; typhoidal, pneumonic, oropharyngeal, and gastrointestinal types; toxemic stage heralds macular, generalized morbilliform eruption, vesicular, pustular, nodular or plaque-like secondary eruption JAAD 49:363–392, 2003; erythema multiformelike rash, crops of red nodules on extremities Cutis 54:279–286, 1994; Medicine 54:252–269, 1985; vesiculopapular lesions of trunk and extremities Photodermatology 2:122–123, 1985 Viral gastroenteritis Whipple’s disease (Tropheryma whipplie) – non-palpable purpura, chronic leg edema, arthralgias; large dilated abdominal lymphatics; diarrhea, weight loss, abdominal pain, generalized hyperpigmentation, pulmonary hypertension, eye, cardiovascular, and neurologic disease Clin Infect Dis 41:519–520,557–559, 2005

INFILTRATIVE DISORDERS Mastocytosis Ped Derm 31:271–275, 2014

INFLAMMATORY DISORDERS Abdominal-cutaneous fistulas J Am Coll Surg 190:588–592, 2000 Crohn’s disease – perianal ulcers, fissures, sinus tracts; rectal bleeding, perianal abscess, abdominal pain, perianal pustule, anal skin tags, scrotal swelling and erythema, labial erythema and edema, perianal erythema, granulomatous cheilitis, fissured lips, angular cheilitis with ulceration, multiple aphthae, cobblestoning of buccal mucosa, linear ulcers of sulci. pyostomatitis vegetans, nodules of gingival and alveolar mucosa Ped Derm 35:566–574, 2018; NEJM 371:2418–2427, 2014; J Pediatr Gastroenterol Nutr 32:339–341,2001; AD 135:439–442, 1999; Eur J Dermatol 8:1238–1240, 1998; JAAD 36:986–988, 1997; NEJM 330:1870, 1994; J R Soc Med 75:414–417, 1982; JAAD 5:689–695, 1981; metastatic JAAD 36:697–704, 1997; fistulae and abscesses Int J Colorectal Dis 11:222–226, 1996; JAAD 10:33–38, 1984; BJD 80:1–8, 1968; penile abscesses Cutis 72:432–437, 2003; pustular pyoderma gangrenosum SKINMed 9:196–198, 2011 Cullen’s sign – periumbilical purpura; hemorrhagic pancreatitis, intra-abdominal bleeding Int J Surg Case Reports 3:143–146, 2012 Erythema nodosum – Salmonella, Shigella, Yersinia Febrile idiopathic lobar panniculitis of childhood – abdominal pain, arthralgia, fever, red nodules of face, legs, trunk, lipoatrophy Ped Derm 31:652, 2014 Pancreatic panniculitis - cutaneous pseudoabscess JAAD 34:362– 364, 1996; Am J Gastroenterol 83:177–179, 1988; Arthritis Rheum 22:547–553, 1979; polyarthritis, simulating cellulitis and gouty arthritis Korean J Gastroenterol 74:175–182, 2019 Pyoderma gangrenosum – ulcerative colitis

Abdominal Pain, Cutaneous Manifestations Pyostomatitis vegetans - lip ulcers; lip swelling with cobblestoning, micropustules NEJM 368:1918, 2013; manifestation of ulcerative colitis Reactive arthritis Grey-Turner sign – purpura of flank associated with retroperitoneal hemorrhage (hemorrhagic pancreatitis) Br J Surg 7:394–395, 1920

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Hypertrichosis lanuginosa – gastric carcinoma Neuroendocrine tumor – facial flushing, abdominal pain, diarrhea; hepatic metastases; elevated chromogranin and 5-hydroxyindoleacetic acid levels; tricuspid regurgitation NEJM 371:260, 2014 Kaposi’s sarcoma NA J Med Sci 5:666–668, 2013 Melanoma Rev Gastroenterol Mex May 3, 2020 Pancreatic carcinoma – pancreatic panniculitis

METABOLIC DISORDERS Acquired zinc deficiency

PRIMARY CUTANEOUS DISEASES

Acrodermatitis enteropathica

Lichen planus – hepatitis C hepatitis

Alpha-1 antitrypsin deficiency – pancreatitis; panniculitis

Umbilical hair sinus – bacterial peritonitis

Celiac disease – oral aphthae Eur J Oral Sci 106:899–906, 1998; BJD 103:111, 1980; acquired cutis laxa JAAD 46:128–130, 2002; BJD 135:130–134, 1996

SYNDROMES

Dumping syndrome – abdominal pain, diarrhea, flushing JAAD 77:391–402, 2017 Fabry’s disease - angiokeratoma corporis diffusum (alpha galactosidase A) – X-linked recessive; initially, telangiectatic macules; perioral telangiectasias Dig Liver Dis 50:429–437, 2018;NEJM 276:1163–1167, 1967 Familial hypercholesterolemia Pancreatitis, acute and chronic; pancreatic panniculitis NEJM 370:1542–1550, 2014 Paroxysmal nocturnal hemoglobinuria – petechiae, ecchymoses, red plaques which become hemorrhagic bullae with necrosis; lesions occur on legs, abdomen, chest, nose, and ears; deficiency of enzymes – decay-accelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL); acquired intravascular hemolytic anemia; due to a drop in pH of serum during sleep; Ham test (acid hemolysis); sucrose lysis test, low leukocyte alkaline phosphatase; anemia, hemoglobinuria (dark urine), increased serum hemoglobin, hemosiderinuria; abdominal pain, recurrent infections, headache, venous thrombosis, progressive bone marrow failure, and ultimately lymphoreticular malignancy (especially, leukemia) Clinical Case Rep 7:175–179, 2019; AD 148:660–662, 2012; AD 138:831–836, 2002; AD 122:1325–1330, 1986; AD 114:560–563, 1978 Porphyrias J Clin Transl Hepatol 3:17–26, 2015; NEJM 370:1542– 1550, 2014; Int J Dermatol 52:1464–1480, 2013   Acute intermittent porphyria Stat Pearls May 23, 2020  Hereditary coproporphyria (ALAD deficiency) Gene Reviews Dec 13, 2012; in lead worker  Plumboporphyria   Variegate porphyria J Emerg Med 43:e235–238, 2012 Ulcerative colitis

NEOPLASTIC DISEASES Plasma cell leukemia – violaceous plaques, abdominal pain, fatigue, anorexia J Drugs in Dermatol 13:994–995, 2014

PARANEOPLASTIC DISORDERS Acanthosis nigricans – gastric cancer Carcinoid syndrome – abdominal pain and urticarial World Allergy Organ J 8:34 Dec 10, 2015

Behcet’s disease – arthritis BJD 159:555–560, 2008; JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999; JAAD 36:689–696, 1997; Ped Derm 11:95–101, 1994 Carcinoid syndrome – pellagrous dermatitis (skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, salivation, lacrimation, abdominal cramping, wheezing, diarrhea BJD 152:71–75, 2005; AD 77:86–90, 1958 Constitutional mismatch repair deficiency syndrome (CMMR-D) – café au lait macules; hypopigmented macules; hematologic malignancies, rhabdomyosarcoma, brain tumors, early onset gastrointestinal tumors; mutations in MLH1, MSH2, MSH6, OR PMS2 BJD 164:245–256, 2011; Hum Genet 124:105–122, 2008; Eur J Hum Genet 16:62–72, 2008; J Med Genet 46:41803420, 2009 Cronkhite-Canada syndrome – gastrointestinal polyposis, nail dystrophy, alopecia, hyperpigmentation of upper extremities or diffuse hyperpigmentation, diarrhea, weight loss, abdominal pain Degos’ disease (malignant atrophic papulosis) - white atrophic papules AD 145:321–326, 2009; BJD 139:708–712, 1998; AD 128:255–260, 1992; lower extremity hypoplasia Turk J Pediatr 43:159–161, 2001; BJD 100:21–36, 1979; Ann DV 79:410–417, 1954; ulceropustular lesions Ann DV 79:410–417, 1954 Ehlers-Danlos syndrome type IV – visceral rupture Familial Mediterranean fever – fever for 6–72 hours; monoarticular arthritis, severe abdominal pain, pleurisy, leukocytoclastic vasculitis; scrotal pain and edema, AA amyloid JAAD 68:834–853, 2013; AD 144:392–402, 2008; Medicine 77:268–297, 1998; AD 134:929–931, 1998; QJMed 75:607–616, 1990; autosomal recessive; erysipelas-­ like erythema - mutation in MEFV/pyrin/marenostrin JAAD 68:834– 853, 2013; JAAD 42:791–795, 2000; AD 136:1487–1494, 2000; mimicking infectious cellulitis; Ann Int Med 142:47–55, 2005; NEJM 350:904–912, 2004; Isr Med Assoc J 1:31–36, 1999; Q J Med 75:607–616, 1990; red patch with pale areas AD 143:1080–1081, 2007; sterile peritonitis Gardner’s syndrome IgG4 disease – sclerosing mesenteritis Muckle–Wells syndrome – abdominal pain Multiple mucosal neuroma syndrome – colonic distention due to intestinal ganglioneuromatosis NEJM 373:756, 2015 Neurofibromatosis BMJ Case Rep 13:e234383 June 3, 2020 NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic self-limiting fever, polyarthritis, polyarthralgia, red plaques of face

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013 Peutz-Jeghers syndrome – intussusception Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) - erythematous patches, tender red plaques, fever, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia, abdominal pain, headache; Irish and Scottish predominance; mutation in TNFRSF1A - gene encoding 55kDa TNF receptor AD 136:1487– 1494, 2000

symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014; right upper quadrant abdominal pain BMJ Case Rep Feb 22, 2017 Vasculitis - with paraproteinemia, inflammatory bowel disease, pregnancy, myeloma, sarcoid JAAD 43:955–957, 2000; leukocytoclastic vasculitis due to chlorzoxazone BJD 150:153, 2004

ABSCESS (STERILE AND NON-STERILE)  UTOIMMUNE AND DISEASES OF IMMUNE A DYSFUNCTION

TOXINS

Agranulocytosis - infantile genetic agranulocytosis – subcutaneous abscesses Acta Paediatr Scand 64:362–368, 1975

Acrodynia (pink disease) - mercury poisoning; acral erythema and pain, hypertension, tachycardia, mental status changes Arch Dis Child 86:453–2002; Ped Derm 21:254–259, 2004; Ann DV 121:309– 314, 1994; profuse sweating; red edematous hands and feet, severe periumbilical pain, irritability Ped Derm 29:199–201, 2012; Pediatr Nephrol 22:903–906, 2009; Arch Dis Child 62:293–295, 1987; Lancet 29:829–830, 1948; Arch Dermatol Syphilol 26:215–237, 1932; Rev Med Fr 3:51–74, 1830

Allergic contact dermatitis – to aluminum in vaccination site Ped Derm 29:68–72, 2012

Ciguatera fish poisoning – marine algae (Gambierdiscus toxicus) sea bass, grouper, red snapper, barracuda, amberjack, surgeonfish (herbivorous species that consume coral); flushing, diarrhea, vomiting, abdominal pain, pruritus, temperature reversal, dysesthesia, diffuse tingling pain, burning tongue, gingiva, teeth, myalgia, weakness, vomiting, dysesthesia, and ataxia; ciguatoxin produced by coral reef dinoflagellate plankton species ingested by herbivorous fish; incubation period is 15 minutes to 3 hours JAAD 55:193– 208, 2006 Lead poisoning NEJM 370:1542–1550, 2016

TRAUMA Ruptured urinary bladder – abdominal distension NEJM 373:1865– 1870, 2015

VASCULAR DISEASES Abdominal arteriovenous fistulae Cutis 87:284–286, 2011 Disseminated intravascular coagulation (DIC) - associated with sepsis, snake envenomation, amniotic fluid embolization, fat emboli, abruptio placentae, severe head injury, Kasabach-Merritt syndrome JAAD 61:325–332, 2009; JAAD 25:882–888, 1991; peripheral symmetric gangrene AD 137:139–140, 2001 Hemophagocytic lymphohistiocytosis (HLH) – abdominal pain, fever NEJM 374:165–173, 2016 Henoch-Schonlein purpura Postgrad Med 131:295–298, 2019; BMC Ped 18:157, 2018; JAAD 43:955–957, 2000; rosettes AD 139:215– 220, 2003 Polyarteritis nodosa - acrocyanosis and/or Raynaud’s phenomenon; livedo reticularis with surrounding erythema; ulcers, papules JAAD 57:840–848, 2007; JAAD 52:1009–1019, 2005; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal

Chediak-Higashi syndrome – photophobia, nystagmus, decreased pigmentation of iris BJD 178:335–349, 2018 Chronic familial neutropenia Chronic granulomatous disease - bacterial abscesses, perianal abscesses JAAD 36:899–907, 1997; AD 130:105–110, 1994; AD 103:351–357, 1971; gene carriers may develop abscesses, hidradenitis suppurativa, and ulcerative stomatitis BJD 178:335– 349, 2018; Ped Derm 3:376–379, 1986; female X-linked carriers of chronic granulomatous disease – infections with Burkholderia cepacia complex, Aspergillus fumigatus, Trichosporon inkin, Nocardia spp. J Allergy Clin Immunol 141:365–371, 2018 Common variable immunodeficiency Ped Derm 26:155–158, 2009; BJD 147:364–367, 2002; J Allergy Clin Immunol 109:581, 1999 Complement deficiencies – C1q Clin Exp Immunol 38:52–63, 1979 Congenital cyclic neutropenia – periodic fevers BJD 178:335–349, 2018; Blood Rev 2:178–185, 1988; Am J Med 61:849–861, 1976 Cyclic neutropenia BJD 178:335–349, 2018; Ped Derm 18:426–432, 2001; Am J Med 61:849–861, 1976 Dock8 deficiency syndrome (dedicator of cytokinesis 8 gene) (autosomal recessive hyper IgE syndrome) – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE, decreased IgM, increased eosinophilia; cold abscesses, recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; warts, dermatitis, asthma, , cutaneous staphylococcal abscesses; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation BJD 178:335–349, 2018; AD 148:79–84, 2012 Hyper-IgE syndrome (Job’s syndrome) – cold abscesses BJD 178:335–349, 2018 Hyper IgM immunodeficiency syndromes - X-linked recessive - perirectal abscesses JAAD 38:191–196, 1998 ICF syndrome – immunodeficiency, centromere instability, and facial anomaly syndrome – cold abscesses BJD 178:335–349, 2018 IL-1 receptor-associated kinase 4 gene (IRAK-4) mutations – cellulitis, abscesses, impetigo JAAD 54:951–983, 2006; Science 299:2076–2079, 2003 IL-10 defect – perianal abscess BJD 178:335–349, 2018

Abscess (Sterile and Non-sterile) Lactoferrin deficient neutrophils (neutrophil-specific granule deficiency) – autosomal recessive Ann Rev Med 36:263–274, 1985; J Clin Immunol 4:23–30, 1984 Leukocyte adhesion deficiency (beta-2 integrin deficiency) – abscesses, cellulitis, skin ulcerations, pyoderma gangrenosum; ulcerative stomatitis BJD 178:335–349, 2018;

DRUG BCG (Bacille-Calmette-Guerin) reactions BJD 164:1402–1403, 2011 Calcium gluconate extravasation AD 138:405–410, 2002; AD 134:97–102, 1998

BJD 139:1064–1067, 1998; J Pediatr 119:343–354, 1991; Ann Rev Med 38: 175–194, 1987; J Infect Dis 152:668–689, 1985; congenital deficiency of leucocyte-adherence glycoproteins (CD11a (LFA-1), CD11b, CD11c, CD18) – necrotic cutaneous abscesses, psoriasiform dermatitis, gingivitis, periodontitis, septicemia, ulcerative stomatitis, pharyngitis, otitis, pneumonia, peritonitis BJD 123:395– 401, 1990

Epidermal growth factor inhibitors – abscess-like lesions JAAD 55:657–670, 2006

Leukocyte glucose-6-phosphatase deficiency J Pediatr 87:1121– 1124, 1975

Interferon-beta injection site JAAD 34:365–367, 1996

Mammalian sterile 20-like 1 deficiency BJD 178:335–349, 2018 Mendelian susceptibility to mycobacterial disease (MSMD) – Mycobacterium bovis, non-tuberculous mycobacteria, Salmonella – mutations in IL-12, interferon gamma, IFNGR1, IFNGR2, STAT1, IL-12B, aIL-12RB1, IKBKG Ped Derm 31:236–240, 2014 Mycobacteriosis (atypical) BJD 178:335–349, 2018   GATA2 deficiency   IFN gammaR1/2 defects   IRF8 defects   ISG15 disease   Macrophages-gp91-phox defect   MSMD (Mendelian susceptibility to mycobacterial disease)   NEMO deficiency   STAT-1 defects

5

Granulocyte colony stimulating factor - cystic acne and hidradenitis suppurativa associated with myelodysplastic syndrome AD 144:643–648, 2008 Infliximab – polyarthritis and abscess formation during infliximab treatment of hidradenitis suppurativa BJD 165:194–198, 2011 Iododerma – carbuncular lesions Australas J Dermatol 28:119–122, 1987 Isotretinoin – lip abscess JAMA Derm 149:960–961, 2013; J Drugs Dermatol 8:1034–1036, 2009 Vemurafenib (BRAF inhibitor) – cystic lesions of face, hidradenitis suppurativa, keratosis pilaris-like eruptions, eruptive melanocytic nevi; hyperkeratotic plantar papules, squamous cell carcinoma; multiple nodules of cheeks; follicular plugging; exuberant seborrheic dermatitis-like hyperkeratosis of face; hand and foot reaction; diffuse spiny follicular hyperkeratosis; cobblestoning of forehead AD 1428:-1429, 2012; JAAD 67:1375–1379, 2012; AD 148:357–361, 2012 Zinc – furuncles at injection site Zyderm collagen implant (bovine collagen) JAAD 25:319–326, 1991

Neutrophilic-specific granule deficiency; mutations in CEBPE, GF11 BJD 178:335–349, 2018 Papillon-Lefevre syndrome – perianal abscess BJD 178:335–349, 2018 Perforating neutrophilic and granulomatous dermatitis of the newborn – cutaneous eruption of immunodeficiency; papules, plaques, vesicles, crusts, ulcers; boggy pustular masses; purpuric lesions; prominent involvement of palms and soles; sparing of trunk Ped Derm 24:211–215, 2007

EXOGENOUS AGENTS Drug abuse, intravenous JAAD 69:135–142, 2013; NEJM 277:473– 475, 1967 Foreign body, including foreign body granuloma Hair sinus – of the hand JAAD 47:S281–282, 2002; barber’s sinus and cyst AD 112:523–524, 1976; of the breast Clin Exp Dermatol 7:445–447, 1982

Transcobalamin II deficiency Primary Immunodeficiencies. Amsterdam: Elsevier 353–362, 1980

Milk injections – suppurative panniculitis Rook p. 2422, 1998, Sixth Edition

Tuftsin deficiency J Pediatr 111:852–854, 1987

Paraffin granuloma Bolognia, p.1477, 2003

X-linked hypogammaglobulinemia – perianal abscess BJD 178:335–349, 2018; Medicine (Baltimore)85:193–202, 2006

Pilonidal sinus - of umbilicus Lancet 2:281–2, 1956; of suprapubic region

X-linked inhibitor of apoptosis-deficiency – perianal abscess BJD 178:335–349, 2018

Silicone granuloma AD 141:13–15, 2005; Derm Surg 27:198–200, 2001

CONGENITAL

INFECTIONS OR INFESTATIONS

Congenital agranulocytosis

Abdominal-cutaneous fistulas J Am Coll Surg 190:588–592, 2000

Fetal scalp electrode placement AD 135:697–203, 1999; JAAD 18: 239–259, 1988; scalp abscess of 3 day old infant Am J Obstet Gynecol 129:185–189, 1977

Abdominal wall abscesses AD 131:275–277, 1995   Candida krusei   Crohn’s disease   Infected lipoma   Post-operative wound infection

First branchial cleft Peristernal dermal sinus connecting to pectoralis major – swelling, suppuration, and pain Ped Derm 37:40–51, 2020 Pre-auricular cyst with secondary infection (Staphylococcus, Proteus, Streptococcus, Peptococcus) J Oral Maxillofac Surg 56:827–831, 1998 Subcutaneous fat necrosis of newborn AD 146:882–885, 2010; Ped Derm 27:317–318, 2010

Abscess in a prepatellar bursa – personal observation Abscess over ECMO port - personal observation Abscess with sepsis - personal observation Acanthamoeba Clin Inf Dis 27:1547–1548, 1998; Clin Inf Dis 20:1207–1216, 1995

6

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Acinetobacter baumannii JAAD 75:1–16, 2016; JAMA Derm 150:905–906, 2014

carbuncle JAAD 14:511–12,1986; Candida krusei AD 131:275–277, 1995

Actinomycosis, multiple species Med J Aust 169:120, 1998; Clin Inf Dis 19:143–145,1994; AD 124:121–126, 1988; Ann Int Med 132:328–332, 1981; JAMA 228:1397–1400, 1974; A. meyeri Clin Inf Dis 22:185–186, 1996

Carbuncle - following herpes zoster - personal observation; perianal - personal observation

Aeromonas hydrophila JAAD 61:733–750, 2009

Chagas’ disease (Trypanosoma cruzi) – chagoma; furuncle-like violaceous lesions with central edema and regional adenopathy JAAD 60:897–925, 2009; Chagas’ disease – megacolon, intestinal perforation; unilateral painful bipalpebral edema, conjunctivitis, local lymphadenopathy, periorbital cellulitis, panniculitis, cardiac involvement JAAD 75:19–30, 2016

African histoplasmosis (Histoplasma duboisii) BJD 82:435–444, 1970 Alternariosis JAAD 52:653–659, 2005; Int J Derm 39:293–295, 2000 Amebic abscess Clin Inf Dis 20:1207–1216, 1995; Pediatrics 71:595–598, 1983; rectal abscess Int J Dermatol 41:676–680, 2002;

Cat scratch disease (suppurative adenopathy) Ped Derm 5:1–9, 1988

Chancroid

Anal gland infection - perianal abscess

Clostridium botulinum – wound botulism in drug addicts Clin Inf Dis 31:1018–1024, 2000

Apophysomyces elegans

Clostridium dificile Clin Inf Dis 20:1560–1562, 1995

Aspergillosis - abscess or kerion-like JAAD 80:869–880, 2019; JAAD 29:654–655, 1993; BJD 85 (suppl):95–97, 1971; A. fumigatus East Afr Med J 75:436–438, 1998; ulcers with satellite abscesses Ped Derm 19:439–444, 2002; A. Flavus – heart transplant patient personal observation

Coccidioidomycosis JAAD 55:929–942, 2006; JAAD 26:79–85, 1992; primary cutaneous coccidioidomycosis JAAD 49:944–949, 2003

Bacillary angiomatosis AD 131:933–936, 1995 Bacille-Calmette-Guerin (BCG) cold abscesses - single or multiple; Ped Derm 208–212, 2000; Ped Derm 14:365–368, 1997; in patient with severe combined immunodeficiency disease – abscesses, nodules, papules and pustules Ped Derm 36:672–676, 2019 Bacteroides – sepsis with abscesses Bilophila wadsworthia J Clin Inf Dis 25 (Suppl 2):S88–93, 1997 Botryomycosis – granulomatous reaction to bacteria with granule formation; single or multiple abscesses of skin and subcutaneous tissue break down to yield multiple sinus tracts; small papule; extremities, perianal sinus tracts, face Cutis 80:45–47, 2007; Int J Dermatol 22:455–459, 1983; AD 115:609–610, 1979 Breast abscess Clin Inf Dis 59:410,454–455, 2014   Anaerobic species in non-puerperal women   Brucella melitensis J Infect 33:219–220, 1996   Cat scratch disease Clin Inf Dis 59:410,454–455, 2014   Cryptococcus neoformans Scand J Infect Dis 34:309–310, 2002   Cystic neutrophilic granulomatous mastitis presenting as recurrent breast abscess; Corynebacterium species include C. kroppenstedtii, C, amycolatum, C. tuberculostearicum, C. accolens, C. striatum, C. minutissimum Clin Inf Dis 59:410, 454–455, 2014   Escherichia coli   Granulomatosis with polyangiitis Acta Clin Belg 54:207–210, 1999   Mycobacterium chelonei   Periareolar pilonidal abscesses  Sarcoidosis Pathologica 102:104–107, 2010   Squamous metaplasia of lactiferous ducts   Staphylococcus aureus – most common cause in lactating women Clin Inf Dis 59:410, 454–455, 2014 Brucellosis (Brucella melitensis) – primary inoculation abscesses Cutis 63:25–27, 1999; AD 117:40–42, 1981; breast abscess J Infect 33:219–220, 1996; testicular abscess with Brucella epididymoorchitis – scrotal swelling, pain, fever, diaphoresis Clin Inf Dis 33:2017–2027, 2001 Campylobacter jejuni - perirectal abscess Candida - Candida albicans Arch Dis Child 59:479–480, 1984; abscess in heroin abusers Dermatologica 177:115–119, 1988; JAAD 16:386–387, 1987; Candida tropicalis - nodular subcutaneous abscesses JAAD 16:623–624, 1987; abscess or kerion-like

Cold abscess/Job’s syndrome Cowpox – human cowpox with fingertip necrosis and arm abscess, lymphangitis, lymphadenopathy Clin Inf Dis 69:179– 181, 2019 Corynebacterium pseudotuberculosis Aust NZ Med 15:85–6, 1985; C. xerosis - abscess and sternal wound infection J Clin Inf Dis 19:1171–1172, 1994 Cryptococcosis Pediatr Infect Dis J 19:85–86, 2000; JAAD 37:116–117, 1997; Cryptococcus albidis – scalp abscess Ped Derm 24:285–288, 2007 Demodex folliculitis – demodectic facial abscesses JAAD 49:S272– 274, 2003; Ann DV 113:1047–1058, 1986 Dental sinus J Am Dent Assoc 130:832–836, 1999; Cutis 43:22–24, 1989; JAAD 2:521–524, 1980; facial abscess Ped Derm 29:421– 425, 2012 Dermatophilus congolensis – contact with infected animals BJD 145:170–171, 2001 Dermatophyte infections - pustules and abscesses JAAD 30:1021–1022, 1994; Trichophyton rubrum, invasive Cutis 67:457–462, 2001 Dissecting cellulitis Dracunculosis Edwardsiella tarda – myonecrosis with cutaneous abscesses Clin Inf Dis 32:143–1433, 2001 Eikenella corrodens – cheek abscess, forehead wound, scalp wound, neck wound, periorbital abscess Clin Inf Dis 33:70–75, 2001; submandibular and cervicofacial abscesses Cutis 60:101– 102, 1997; thigh abscess Diabetes Care 19:1011–1013, 1996 Enterobius vermicularis - perianal abscesses Cutis 71:268–270, 2003 Escherichia coli Eugonic fermenter (EF-4) – dog bites J Clin Microbiol 8:667–672, 1978 Exophiala species Exserohilum rostratum JAAD 28:340–344, 1993 Fasciola hepatica (fluke parasite) JAAD 42:900–902, 2000 Felon Filariasis – abscesses from reactions to adult filariae Dermatol Clin 7:313–321, 1989

Abscess (Sterile and Non-sterile)

7

Folliculitis decalvans

Legionella micdadei Ann Int Med 102:630–632, 1985

Fournier’s gangrene – may start as perirectal abscess Surgery 91:49–51, 1982 Frontal sinusitis with abscess

Leishmaniasis (L. major) - acute cutaneous form (wet, rural, zoonotic form); localized furuncle-like nodule JAAD 73:897–908, 2015

Furunculosis J Drugs in Dermatol 12:369–374, 2013

Listeria monocytogenes J Clin Inf Dis 19:988–989, 1994

Fusarium solani Cutis 63:267–270, 1999

Lymphogranuloma venereum – Jersild syndrome – perirectal abscesses, fistulae, sclerosis JAAD 54:559–578, 2006; inguinal adenitis with abscess formation and draining chronic sinus tracts; rectal syndrome in women with pelvic adenopathy, periproctitis with rectal stricture and fistulae; esthiomene – scarring and fistulae of the buttocks and thighs with elephantiasic lymphedema of the vulva; lymphatics may develop abscesses which drain and form ulcers Int J Dermatol 15:26–33, 1976

Fusobacterium – abscesses with necrosis Gemella morbillorum Acta DV 79:398, 1999 Glanders (melioidosis) – Burkholderia (Pseudomonas) mallei – cellulitis which ulcerates with purulent foul-smelling discharge, regional lymphatics become abscesses; nasal and palatal necrosis and destruction; metastatic papules, pustules, bullae over joints and face, then ulcerate; deep abscesses with sinus tracts occur; polyarthritis, septic arthritis, meningitis, pneumonia Clin Inf Dis 31:981–986, 2000; single or multiple abscesses AD 135:311–322, 1999 Gnathostomiasis JAAD 33:825–828, 1995 Gram negative enteric bacteria - perianal abscess Gram negative web space infection with abscess - personal observation Hafnei alvei Clin Inf Dis 20:1426, 1995 Hemophilus influenzae - hand abscesses with oropharyngeal infection J Hand Surg 11A:844–846, 1986 Histoplasmosis Diagnostic Challenges Vol V;77–79, 1994; BJD 82:435–447, 1970 Stye (hordeolum) – staphylococcal abscess of eyelid margin Intersphincteric ulcers of men having sex with men (MSM) Br J Surg 76:1064–1066, 1989 Intravenous drug users Clin Inf Dis 33:35–40, 2001  Anaerobes   Fusobacterium nucleatum   Peptostreptococcus micros   Actinomyces odontolyticus   Pigmented Prevotella  Non-anaerobes   Staphylococcus aureus   Streptococcus milleri group, viridans group, group A   Facultative gram-negative bacteria Abscesses in non-intravenous drug users  Anaerobes   Peptostreptococcus (P. magnus, P. micros, P. saccharolyticus)   Pigmented Prevotella   Actinomyces species   Fusobacterium nucleatum  Non-anaerobes   Staphylococcus aureus    Streptococcus - S. milleri group, viridans group, group A Kerion – crusted nodules and abscess of scalp Ped Derm 28:655– 657, 2011 Kerion-like lesions JAAD 29:654–655, 1993     Aspergillus and rhizopus infection in AIDS JAAD 26:1017, 1991    Candidal carbuncles     Metastatic adenocarcinoma to scalp JAAD 29:654–655, 1993 Lacrimal gland abscess – adjacent to medial canthus Lactation mastitis (breast feeding) - cracked nipples; deep abscesses, mastitis JAMA 289:1609–1612, 2003 Lagochilascaris minor – subcutaneous abscesses; Surinam and Central America Rook p.1395, 1998, Sixth Edition

Melioidosis – Burkholderia pseudomallei – especially found in Thailand; pustules or subcutaneous abscesses JAAD 75:1–16, 2016; Clin Inf Dis 60:21–26, 2015; Clin Inf Dis 60:243–250, 2015; Ped Derm 29:692, 2012; JAAD 54:559–578, 2006; Clin Inf Dis 40:988–989,1053–1054, 2005 Molluscum contagiosum AD 148:1257–1264, 2012; JAAD 43:409– 432, 2000; Ped Derm 6:118–121, 1989; inflammatory reaction surrounding molluscum contagiosum lesions due to immune reconstitution inflammatory syndrome (IRIS) Ped Derm 27:631–634, 2010 Mucormycosis Mycetoma – early in course; sterile abscesses late in course JAAD 53:931–951, 2005; Hautarzt 45:402–405, 1994; scalp abscesses due to Microsporum canis (pseudomycetoma) Cutis 78:473–475, 2006; M. canis and Trichophyton mentagrophytes Mycopathologia 81:41–48, 1983 Mycobacterium abscessus – breast abscesses due to adulterated intramammary silicone injections JAAD 50:450–454, 2004; post-injection abscesses Clin Inf Dis 24:1147–1153, 1997; Clin Inf Dis 19:263–273, 1994; AD 142:1287–1292, 2006; Am J Respir Crit Care Med 156 (pt 2):S1–S25, 1997; Rev Infect Dis 5:657–679, 1983; leg abscess Ped Derm 23:128–131, 2006; pedicure-associated furunculosis Clin Inf Dis 53:787–792, 2011; abscess Ped Derm 32:488–494, 2015 Mycobacterium avium complex – abscess J Drugs Dermatol 13:1491–1493, 2014; Rev Inf Dis 11:625–628, 1989 Mycobacterium avium-intracellulare BJD 136:121–123, 1997; Clin Inf Dis 19:263–273, 1994; JAAD 27:1019, 1992; AD 124:1545– 1549, 1988; perianal abscess Mycobacterium bollettii – leg plaques, pustules, and abscesses due to foot baths for pedicures AD 147:454–458, 2011 Mycobacterium chelonei-fortuitum – BJD 171:79–89, 2014; JAAD 60:177–179, 2009; AD 142:1287–1292, 2006; Am J Respir Crit Care Med 156 (pt 2):S1–S25, 1997; JAAD 30:269–270, 1994; Clin Inf Dis 19:263–273, 1994; AD 122:695–697, 1986; Rev Infect Dis 5:657–679, 1983; Medicine 60:95–109, 1981; ; pedicure-associated furunculosis Clin Inf Dis 53:787–792, 2011; facial abscess Ped Inf Dis 3:335–340, 1984; cold abscesses; breast abscess Clin Inf Dis 26:760–761, 1998; multiple draining abscesses of leg AD 143:951–952, 2007 Mycobacterium fortuitum – AD 142:1287–1292, 2006; Am J Respir Crit Care Med 156 (pt 2):S1–S25, 1997; Rev Infect Dis 5:657–679, 1983; injection abscesses Lancet ii:691, 1969; leg abscesses from foot bath in nail salon JAAD 54:520–524, 2006; NEJM 346:1366– 1371, 2002; at sites of subcutaneous insulin infusion BJD 171:418– 420, 2014; after amateur tattooing J Med Assoc Thai 95:834–837, 2012; after treatment of molluscum contagiosum Infect Chemother 45:85–93, 2013; J Eur Acad Dermatol and Venereol 24:604–606, 2010

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Mycobacterium haemophilum Ped Derm 32:488–494, 2015; Ann Int Med 97:723–724, 1982

Myositis - bacterial, filarial, post-traumatic

Mycobacterium kansasii Ped Derm 32:488–494, 2015; JAAD 41:854–856, 1999; JAAD 36:497–499, 1997; Clin Inf Dis 19:263– 273, 1994

Neisseria gonorrhea - newborn with gonococcal scalp abscess South Med J 73:396–397, 1980; Am J Obstet Gynecol 127:437– 438, 1977; foot abscess Clin Orthop 234:209–210, 1988; Med J Aust 141:902, 1984; gonococcal furunculoid lesions of penis and scrotum Br J Inf Dis 49:364–367, 1973

Mycobacterium leprae - peripheral nerve abscess Indian J Lepr 69:143–147, 1997; Acta Leprol 10:45–50, 1996; suppuration of erythema nodosum leprosum Rook p.1227, 1998, Sixth Edition Mycobacterium mageritense J Clin Microbiol 42:1813–1817, 2004 Mycobacterium marinum – tender red nodule or pustule which evolves into crusted ulcer with underlying suppurative abscess Cutis 79:33–36, 2007; Clin Inf Dis 19:263–273, 1994 Mycobacterium massiliense – leg plaques, pustules, and abscesses due to foot baths for pedicures AD 147:454–458, 2011 Mycobacterium mucogenicum – suppurative nodule Med Cl (Barcelona) 132:370, 2009 Mycobacterium peregrinum Mycobacterium scrofulaceum AD 138:689–694, 2002; Clin Inf Dis 19:263–273, 1994; AD 123:369–370, 1987; Mycobacterium smegmatis Mycobacterium szulgai – carbuncle Tubercle 66:65–67, 1985 Mycobacterium thermoresistible Mycobacterium tuberculosis – scrofuloderma – neck abscess JAMA Derm 150:909–910, 2014; Cutis 85:85–89, 2010; abscess Ped Derm 30:7–16, 2013; hot abscess; cold abscess (tuberculous gumma) SKINmed 10:28–33, 2012; tuberculous gumma (metastatic tuberculous ulcer) – firm subcutaneous nodule or fluctuant swelling breaks down to form undermined ulcer; bluish surrounding skin bound to the inflammatory mass; sporotrichoid lesions along draining lymphatics; extremities more than trunk Am J Clin Dermatol 3:319–328, 2002; BJD 142:387–388, 2000; Scand J Infect Dis 32:37–40, 2000; Scand J Inf Dis 35:149–152, 1993; JAAD 19:1067– 1072, 1988; JAAD 6:101–106, 1982; Semin Hosp Paris 43:868–888, 1967; of the neck BJD 142:387–388, 2000; paradoxical subcutaneous tuberculous abscess J Clin Inf Dis 26:231–232, 1998; J Clin Inf Dis 24:734, 1997; cutaneous metastatic tuberculous abscess Ped Derm 19:90–91, 2002; Cutis 66:277–279, 2000; lupus vulgaris Mycobacterium ulcerans Derm Clinics 17:151–185, 1999 Myiasis, furuncular – face, scalp, arms, legs; house fly JAAD 75:19–30, 2016; BJD 76:218–222, 1964; New World screw worm (Cochliomyia), Old World screw worm (Chrysomya), Tumbu fly, skin maggot fly, putzi fly, mango fly, ver du Cayor (Cordyloba anthropophaga)(tropical Africa) JAAD 58:907–926, 2008; Int J Derm 34:624–626, 1995; BJD 85:226–231, 1971; black blowflies (Phormia) J Med Entomol 23:578–579, 1986; greenbottle (Lucilia), bluebottle (Calliphora), flesh flies (Sarcophaga, Wohlfartia vigil) (eastern and central North America, central and southern Europe, Russia, Pakistan) JAAD 58:907–926, 2008; Neurosurgery 18:361– 362, 1986; Wohlfartia opaca (western and southwest North America) JAAD 58:907–926, 2008; rabbit or rodent botflies (Cuterebra spp.)(eastern US, Ontario, Pacific Northwest) JAAD 58:907–926, 2008; JAAD 21:763–772, 1989; Wohlfartia magnifica – scalp abscess Cutis 82:396–398, 2008; human botflies (Dermatobia hominis)(Central and South America) JAAD 58:907–926, 2008; JAAD 57:716–718, 2007; AD 121:1195–1196, 1985; sheep nostril fly (Oestrus ovis) Ann Trop Med Parasitol 82:221–223, 1988; warble flies (Hypoderma) – migratory myiasis AD 90:180–184, 1964; AD 126:199–202, 1990; myiasis – creeping eruption (migratory myiasis); horse botfly (Gasterophilus)(worldwide) JAAD 58:907– 926, 2008; heel fly, gad fly, cattle grubs (Hypoderma bovis, lineatum) JAAD 58:907–926, 2008; BJD 143:912–914, 2000; blowfly JAAD 67:331–344, 2012; furunculoid myiasis (tumbu fly) – pore overlying furuncular lesion JAMA Derm 154:737–738, 2018

Necrotizing fasciitis JAAD 20:774–781, 1989

Nocardiosis - Cutis 89:75–77, 2012; actinomycetomas of trunk, extremities, feet– N. brasiliensis, N. otitidiscaviarum, N. asteroides BJD 156:308–311, 2007; J Dermatol 26:829–833, 1999; AD 130:243–248, 1994; JAAD 21:137–139, 1989; JAAD 13:125–133, 1985; N. brasiliensis J Inf Dis 134:286–289, 1976; N. asteroides BJD 144:639–641, 2001; JAAD 39:793–794, 1998; J Clin Inf Dis 24:1154–1160, 1997; N. farcinica Ann Med Interne (Paris) 150:582– 584, 1999; JAAD 38:874–876, 1998; N. otidiscaviarum Clin Inf Dis 20:1266–1270, 1995; J Trop Med Hyg 98:395–403, 1995; N. otitidiscaviarum – multiple abscesses with draining sinus tracts AD 143:1086–1087, 2007; lymphocutaneous nocardiosis – crusted verrucous plaques with sporotrichoid nodules, abscesses, and pustules Cutis 85:73–76, 2010; nocardia abscess with osteomyelitis - personal observation North American blastomycosis (Blastomyces dermatitidis) JAAD 21:1285–1293, 1989 Olecranson bursal sac abscess - personal observation Orf Ann Chir Main 5:129–132, 1986 Osteomyelitis Paracoccidioidomycosis – hematogenous or lymphatic spread Rook p.1370, 1998, Sixth Edition Paragonimiasis - cold abscesses Rev Ecuator Hig Med Trop 36:69–82, 1979 Paronychial abscess Dermatol Clin 33:207–241, 2015 Parotid gland abscess – Staphylococcus aureus; personal observation Pasteurella multocida – periocular abscess and cellulitis; tenosynovitis, septic arthritis Am J Ophthalmol 128:514–515, 1999; JAAD 33:1019–1029, 1995 Perianal abscesses   Anal gland infection   Campylobacter jejuni   Enterobius vermicularis   Gram negative enteric bacteria   IL-10 defect BJD 178:335–349, 2018   Mycobacterium avium   Papillon-Lefevre syndrome BJD 178:335–349, 2018   X-linked agammaglobulinemia BJD 178:335–349, 2018   X-linked inhibitor of apoptosis-deficiency BJD 178:335–349, 2018 Perifolliculitis capitis Perirectal abscess NEJM 343:794–800, 2000  Actinomycosis  Carcinoma   Crohn’s disease   Cryptoglandular infection   Foreign body  Leukemia  Lymphoma   Lymphogranuloma venereum   Mycobacterium tuberculosis   Pelvic inflammation  Radiation   Trauma (operative, enema, impalement) Phaeohyphomycosis JAAD 19:478–481, 1988; AD 123:1346–1350, 1987; subcutaneous phaeohyphomycosis JAAD 36:863–866, 1997;

Abscess (Sterile and Non-sterile)

9

diffuse infiltrated pigmented plaques; subcutaneous cysts, abscesses, ulcerated plaques, hemorrhagic pustules, necrotic papulonodules, cellulitis JAAD 75:19–30, 2016; JAAD 40:364–366, 1999; JAAD 28:34–44, 1993; AD 127:721–726, 1991; JAAD 19:478–481, 1988; AD 123:1346–1350, 1987

Staphylococcus aureus, coagulase-negative (staphylococcus epidermidis) – abscesses of scalp and breast in the neonate Textbook of Neonatal Dermatology, p.190, 2001

Phialophora

Sternoclavicular joint septic arthritis J Clin Inf Dis 19:964–966, 1994

Phlegmon - perirectal abscess - Pseudomonas Clin Inf Dis 20:302–308, 1995; Serratia marcescens - personal observation

Streptococcus milleri group (S. intermedius, S.constellatus, S. anginosus) Clin Inf Dis 32:1511–1515, 2001

Porphyromonas asaccharolytica – abscesses below waistline

Streptococcus pneumoniae Clin Inf Dis 21:697–698, 1995; neck Clin Inf Dis 19:149–151, 1994

Pott’s puffy tumor – subperiosteal abscess of forehead with frontal bone osteomyelitis secondary to frontal sinusitis Ped Derm 27:406–408, 2010  Differential diagnosis of Pott’s puffy tumor Ped Derm 27:406–408, 2010   Carbuncle   Dermoid cyst   Epidermoid cyst    Giant frontal mucocele   Infected hematoma    Intracranial malignant meningioma   Intraosseous lipoma   Lipoblastoma   Lipoma    Superficial temporal artery pseudoaneurysm Prevotella species – abscesses below waistline J Clin Inf Dis 25 (suppl 2):S88–93, 1997 Protothecosis AD 112:829–832, 1976; draining abscesses of cheeks following fat injection J Clin Aesthet Dermatol 12:13–16, 2019 Pseudomonas sepsis Am J Med 80:525–529, 1986 Pyomyositis JAAD 51:308–314, 2004 Rat bite fever (Streptobacillus moniliformis) - acral hemorrhagic pustules and abscesses JAAD 38:330–332, 1998; BJD 129:95–96, 1993; chronic abscesses AD 148:1411–1416, 2012; MMWR 53:1198–1202, 2005; Cleveland Clin Q 52 (2):203–205, 1985; Pediatr Clin N Am 26:377–411, 1979 Rhizopus in AIDS - kerion-like JAAD 26:1017, 1992 Rhodococcus equi Clin Inf Dis 34:1379–1385, 2002; Clin Inf Dis 20:478–479, 1995 Salmonella – S. enteritidis J Infect 27:204–205, 1993; JR Soc Med 83:190, 1990; neck abscess Head Neck 13:153–155, 1991; S. typhimurium Scalp abscess - subgaleal abscess JAAD 18:239–259, 1988; posterior scalp abscess due to sinusitis-associated epidural abscess Int J Pediatr Otorhinolaryngol 43:147–151, 1998; neonatal abscess - coagulase-negative staphylococcus Textbook of Neonatal Dermatology, p.190, 2001

Staphylococcus lugdunensis – associated with molluscum contagiosum Ped Derm 32:289–291, 2015

Streptococcus pyogenes – soft tissue infections Clin Inf Dis 61:1840–1849, 2015 Subungual abscess - personal observation Sweat gland periporitis JAAD 38:1–17, 1998 Sycosis – deep staphylococcal folliculitis Dermatol Wochenschr 152:153–167, 1966 Syphilis - syphilitic gumma Talaromyces marneffei (Penicillium marneffei) – facial abscess JAMA Derm 155:1195–1197, 2019; JAAD 37:450–472, 1997 Tinea capitis (T. verrucosum, T. mentagrophytes) – kerion AD 114:371–372, 1978; tinea capitis mimicking dissecting cellulitis – alopecia and inflammatory nodules of scalp Ped Derm 30:753–754, 2013 Tinea corporis, invasive(T.violaceum) BJD 101:177–183, 1979 Tinea faciei Clin Exp Dermatol 25:608–610, 2000 Toxocariasis JAAD 33:825–828, 1995 Trichomonas – penile abscesses Bull Soc Gr Dermatol Syphiligr 76:345, 1969 Trypanosomiasis – trypanosomal chancre – red tender 2–5 cm nodule with blister on surface of forearm or leg Tsukamurella paurometobolum J Clin Inf Dis 23:839–840, 1996 Tularemia - bubo Tungiasis – abscess-like lesion of sole or between toes JAAD 67:331–344, 2012; AD 141:389–394, 2005; JAAD 20:941–944, 1989; JAAD 15:117–119, 1986 Yersinia enterocolitica Yersinia species (plague) - near bubo Clin Inf Dis 19:655–663, 1994; J Inf Dis 165:740–743, 1992; Yersinia pestis – carbuncle AD 135:311–322, 1999 Xylohypha emmonsii Zygomycosis - primary cutaneous - including Apophysomyces elegans, Saksenaza vasiformis J Clin Inf Dis 24:580–583, 1997

Scrotal abscess - bacterial, filariasis, Guinea worm, tumbu fly

INFLAMMATORY DISORDERS

Serratia marcescens - frontal sinusitis with abscess; cutaneous abscess Cutis 66:461–463, 2000; JAAD 41:319–321, 1999; multiple abscesses JAAD 58:891–893, 2008

Acute dacryocystitis - lacrimal gland inflammation Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.189

Sparganosis

Crohn’s disease – perianal abscess Ped Derm 35:566–574, 2018; metastatic - red papules and plaques with overlying scale/crust; red scaly plaque with shallow ulcer; red plaques and nodules; abscesslike lesions JAAD 71:804–813, 2014; J Eur Acad Dermatol Venereol 15:343–345, 2001; JAAD 36:697–704, 1997; fistulae and abscesses Int J Colorectal Dis 11:222–226, 1996; JAAD 10:33–38, 1984; BJD 80:1–8, 1968; penile abscesses Cutis 72:432–437, 2003

Sporotrichosis - hot and cold abscesses Derm Clinics 17:151–185, 1999; perirectal abscess Am Rev Respir Dis 112:119–123, 1975 Staphylococcus aureus – abscess (furuncle) – face, neck, arms, wrists, fingers (including felon), buttocks, anogenital area NEJM 370:1039–1047, 2014; J Drugs in Dermatol 13:119–124, 2014; methicillin-resistant S. aureus Cutis 78:113–116, 2006; MRSA abscess – necrotic papule with surrounding erythema AD 144:952– 954, 2008; carbuncle; multiple abscesses in bone marrow transplant patient; intravenous drug abuse - soft tissue infections Clin Inf Dis 61:1840–1849, 2015

Cystic neutrophilic granulomatous mastitis – abscess-like lesion of breast; Corynebacterium kroppenstedtii, C. amycolatum, C. tuberculostearicum, C. accolens, C. striatum, C. minutissimum Clin Inf Dis 59:410,454–455, 2014

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Dissecting cellulitis of the scalp (perifolliculitis capitis abscedens et suffodiens) – painful, sterile abscesses with interconnecting sinus tracts; scarring; keloids JAMA Derm 152:1280–1281, 2016; JAAD 62:534–536, 2010; JAAD 23:752–753, 1990; Dermatol Clin 6:387–395, 1988; Ann Plast Surg 18:230–237, 1987; Cutis 32:378– 380, 1983; Minn Med 34:319–325, 1951; AD 23:503–518, 1931

METABOLIC DISEASES

Granulomatous mastitis – abscess, sinus tract, or subcutaneous nodule of breast The Breast Journal 14:588–590, 2008

Pancreatic panniculitis - cutaneous pseudoabscess NEJM 375:1972–1981, 2016; Rook p. 2414, 1998, Sixth Edition; JAAD 34:362–364, 1996; Am J Gastroenterol 83:177–179, 1988; Arthritis Rheum 22:547–553, 1979

Hidradenitis suppurativa – inflammatory nodules JAMA Derm 149:1192–1194, 2013; BJD 165:415–418, 2011; BJD 162:195–197, 2010; JAAD 62:205–217, 2010; BJD 161:831–839, 2009; AD 145:580–584, 2009; JAAD 60:539–561, 2009; Ped Derm 24:465– 473, 2007; AD 142:1110–1112, 2006; Derm Surg 26:638–643,3207, 2000; BJD 141:231–239, 1999  Diseases associated with hidradenitis suppurativa: JAAD 60:539–561, 2009   Acanthosis nigricans   Acne conglobata    Acne vulgaris Br Med J 292:245–248, 1986; Surg Gynecol Obstet 95:455–464, 1952   Bazex-Dupre-Christol syndrome    Crohn’s disease Inflammatory Bowel Dis 7:33–326, 2001; Int J Colorectal Dis 8:117–119, 1993; BJD 126:523, 1992    Dissecting cellulitis of the scalp    Dowling-Degos disease Clin Exp Dermatol 31:454–456, 2006; Clin Exp Dermaol 29:622–624, 2004; Hautarzt 52:642–645, 2001; Australas J Dermatol 38:209–211, 1997; Clin Exp Dermatol 21:305–306, 1996; Ann DV 120:120:705–708, 1993; JAAD 24:888–892, 1991; Cutis 45:446–450, 1990   Fox-Fordyce disease JID 31:127–135, 1958   Interstitial keratitis AD 95:473–475, 1967    Keratitis-ichthyosis-deafness syndrome Eur J Dermatol 15:347–352, 2005; JAAD 51:377–382, 2004    Obesity Acta DV 85:225–232, 2005; J Eur Acad Dermatol Venereol 17:276–279, 2003    Pachyonychia congenita JID Symp Proc 10:3–17, 2005; BJD 123:663–666, 1990; JAAD 19:705–711, 1988   PAPA (pyogenic arthritis, pyoderma gangrenosum, acne) syndrome Mayo Clin roc 72:611–615, 1997    Pilonidal cysts and sinuses   Pyoderma gangrenosum   Reflex sympathetic dystrophy Arch Phys Med Rehabil 82:412–414, 2001   SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome J Clin Rheumatol 8:13–22, 2002    Scrotal elephantiasis    Smoking Acta DV 85:225–232, 2005; J Cut Med Surg 8:415– 423, 2004; J Eur Acad Dermatol Venereol 17:276–279, 2003; Dermatology 198:261–264, 1999 Mamillary fistula (periareolar abscess) Br J Surg 73:367–368, 1986 Panniculitis Pyoderma fistulans sinifica (fox den disease) Clin Inf Dis 21:162– 170, 1995

Alpha-1 antitrypsin deficiency-associated panniculitis JAAD 51:645–655, 2004; AD 123:1655–1661, 1987 Niemann-Pick disease - suppurative lesions of the face Rook p. 2644, 1998, Sixth Edition

NEOPLASTIC DISORDERS Anorectal carcinoma - ischiorectal abscess Br J Med 285:1393, 1982; anal squamous cell carcinoma in situ J Clin Inf Dis 21:603– 607, 1995 Epidermoid cyst, inflamed (ruptured)/infected Extramammary Paget’s disease – may resemble ischiorectal abscess Rook p.3181, 1998, Sixth Edition Giant condyloma of Buschke and Lowenstein AD 136:707–710, 2000 Kaposi’s sarcoma Lipoma - inflamed/infected Lymphoma - CTCL JAAD 33:850–851, 1995; CD30+ large T cell lymphoma of upper lip Br J Oral Maxillofac Surg 35:193–195, 1997; primary B-cell lymphoma – abscess of lower back JAAD 55:S24–27, 2006; cutaneous extranodal natural killer T-cell lymphoma – multiple violaceous or red nodules of extremities, subcutaneous nodules, cellulitis, abscess-like lesions JAAD 70:1002–1009, 2014 Metastases – necrotic fluctuant metastasis mimicking abscess personal observation; to scalp - kerion-like JAAD 29:654–655, 1993; Metastasis – necrotic fluctuant metastasis mimicking abscess - personal observation Myxoid cyst with secondary Staphylococcus aureus - personal observation Perforated intra-abdominal tumor - abdominal wall abscess AD 131:275–277, 1995 Squamous cell carcinoma - finger lesion mimicking abscess Scand J Plast Reconstr Surg Hand Surg 34:91–92, 2000

PRIMARY CUTANEOUS DISEASE Acne keloidalis nuchae JAAD 39:661, 1998 Cheilitis glandularis (Volkmann’s cheilitis) – enlarged lip with crusts and scale; deep-seated abscesses and fistulae J Derm Surg 1:372–375, 1985

Pyodermia chronica glutealis – hidradenitis suppurativa like draining nodules in genitofemoral region and/or buttocks J Dermatol 25:242–245, 1998

Malakoplakia – perianal nodules, vulvar nodules, skin colored nodules, ulcerations, abscesses, red papules, masses Dermatol Online June 15, 2019; Arch Pathol Lab Med 132:113–117, 2008; AD 134:244–245, 1998; Am J Dermatopathol 20:185–188, 1998; JAAD 34:325–332, 1996

Pyoderma gangrenosum – with granulomatosis and polyangiitis personal observation

Pyoderma faciale (form of acne rosacea) – sudden onset of nodules, abscesses, sinuses AD 128:1611–1617, 1992

Subcutaneous fat necrosis of the newborn Cutis 70:169–173, 2002 Ulcerative colitis - sterile abscesses JAAD 42:363–365, 2000

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis – fluctuant subcutaneous lesions JAAD 1:391–407, 1979; factitial injection of hydrocarbons AD 128:997– 998, 1992

Acanthosis Nigricans-Like Lesions

SYNDROMES Anti-phospholipid antibody syndrome – sterile abscesses Cutis 283–286, 2001 Behcet’s syndrome JAAD 40:1–18, 1999 Chediak-Higashi syndrome – photophobia, nystagmus, decreased iris pigmentation, neutropenia, hyperglobulinemia, decreased platelet dense bodies, giant inclusion bodies; mutation in LYST BJD 178:335–349, 2018 Chronic granulomatous disease BJD 178:335–349, 2018 Down’s syndrome – furunculosis Griscelli syndrome Am J Med 65:691–702, 1978 Hyper IgE syndrome (Job’s, Buckley’s, Quie-Hill syndromes (allergic rhinitis)) – autosomal dominant; dermatitis, cold abscesses of neck and trunk, coarse facial skin with broad nose; rough thickened skin with prominent follicular ostia; atrophoderma vermiculatum; retained primary dentition, bone abnormalities, cyst-forming pneumonia, elevated IgE levels; papular, pustular, excoriated dermatitis of scalp, buttocks, neck, axillae, groin; furunculosis; folliculitis-like papular and papulopustular lesions; oral candida; chronic paronychia; growth failure; otitis media common; STAT3 (transcription 3 gene activator and signal transducer) mutations (abnormality of JAK-STAT cytokine signaling pathway BJD 178:335–349, 2018; Ped Derm 30:621–622, 2013; JAAD 65:1167–1172, 2011; NEJM 357:1608–1619, 2007; JAAD 54:855–865, 2006; Dermatol Therapy 18:176–183, 2005; AD 140:1119–1125, 2004; Pediatr 141:572–575, 2002; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983 IRAK-4 deficiency (homozygous mutations of IL-receptorassociated kinase 4 gene) – cutaneous infections with Staphylococcus aureus; abscesses, cellulitis, impetigo JAAD 54:951–983, 2006 Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990; JAAD 23:385–388, 1990; JAAD 19:1124–1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915 Leukocyte adhesion deficiency – lack of pus, abnormal wound healing; mutations in TGB2, FERMT3, SLC3C1 BJD 178:335–349, 2018 NOMID syndrome (neonatal onset multisystem inflammatory disease) PAPA syndrome – pyoderma gangrenosum, cystic acne, aseptic arthritis; sterile abscesses at injection sites; mutation in CD2 binding protein-1 Am J Clin Dermatol 18:555–562, 2017; Ped Derm 22:262–265, 2005; Proc Natl Acad Sci USA 100:13501–13506, 2003; Mayo Clin Proc 72:611–615, 1997 PAPASH syndrome – pyogenic arthritis, pyoderma gangrenosum, acne, hidradenitis suppurativa; autoinflammatory syndrome; mutation in PSTPIP1 gene JAMA Derm 149:762–764, 2013

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Papillon-Lefevre syndrome – abscesses and pneumonia Cutis 93:193–198, 2014; Ped Derm 18:45–47, 2001; Curr Prob in Derm VIII:41–96, 1996; Ped Derm 14:354–357, 1994 PASH syndrome (pyoderma gangrenosum, acne, and hidradenitis suppurativa) BJD 176:1588–1598, 2017; JAAD 66:409–415, 2012 Rosai-Dorfman disease – hidradenitis suppurativa-like lesions Ped Derm 4:247–253, 1987 SAPHO syndrome - palmoplantar pustulosis with sternoclavicular hyperostosis; acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis Sem Arthr Rheum 42:254–265, 2012; Cutis 71:63–67, 2003; Curr Opinion Rheumatol 15:61–69, 2003; Cutis 64:253–258, 1999; Cutis 62:75–76, 1998; Rev Rheum Mol Osteoarthritic 54:187–196, 1987; Ann Rev Rheum Dis 40:547–553, 1981 Schwachman-Diamond syndrome – periodontal disease and caries; abscesses, short stature, delayed puberty, skeletal changes, pancreatic exocrine deficiency, pancytopenia, failure to thrive, hepatomegaly, pneumonia, otitis media, osteomyelitis Ped Derm 28:568–569, 2011 Steatocystoma multiplex Sweet’s syndrome – abscess-like lesions J Dermatol 27:794–797, 2000; JAAD 31:535–556, 1994 WHIM syndrome – warts, hypogammaglobulinemia, infections, myelokathexis (neutrophil retention in bone marrow); abscesses, sinusitis, otitis media, pneumonia; chronic neutropenia; mutation in chemokine receptor CXCR4 family gene Br J Haematol 164:15–23, 2014; JAAD 66:292–311, 2012; Curr Opin Hematol 16:20–26, 2009; Ped Derm 26:155–158, 2009; AD 144:366–372, 2008; Nat Genet 34:70–74, 2003; J Biol Chem 276:42826–42833, 2001 Wiskott-Aldrich syndrome Int J Dermatol 24:77–81, 1985

TRAUMA Body piercing Ann Plast Surg 45:374–381, 2000 Drug addiction - skin popping; abscesses with ulceration BJD 150:1–10, 2004 Injection of chemotherapy into intra-abdominal fat space - abdominal wall abscess Complication of liposuction

VASCULAR Granulomatosis with polyangiitis – abscess-like pyoderma gangrenosum Pseudo-Kaposi’s sarcoma Vascular anomaly

ACANTHOSIS NIGRICANS-LIKE LESIONS JAAD 57:502–508, 2007

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE FUNCTION Dermatomyositis - longstanding dermatomyositis with lipodystrophylike appearance (hirsutism, loss of subcutaneous tissue, acanthosis

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nigricans) JAAD 57:502–508, 2007; J Rheumatol 23:1487–1488, 1996 Lupus erythematosus JAAD 57:502–508, 2007; Lupus 6:275–278, 1997 Pemphigus foliaceus - acanthosis nigricans-like changes Pemphigus vulgaris J Dermatol 8:550–552, 1998; Dermatology 185:309–310, 1992; AD 118:115–116, 1982 Scleroderma – axillary verrucous pigmentation JAAD 57:502–508, 2007; Br Med J ii:1642–1645, 1966

DEGENERATIVE DISEASES Pyramidal tract degeneration JAAD 57:502–508, 2007

DRUG-INDUCED Birth control pills AD 111:1069, 1975 Corticosteroids JAAD 57:502–508, 2007 Diethylstilbestrol Fusidic acid JAAD 28:501–502, 1993 Heroin JAAD 57:502–508, 2007 Hydantoin derivatives JAAD 57:502–508, 2007 Insulin reaction – localized acanthosis nigricans at sites of injection AD 144:126–127, 2008; AD 122:1054–1056, 1986 Melphalan flexural dermatitis - personal observation Methyl-testosterone JAAD 57:502–508, 2007 Niacinamide Nicotinic acid Dermatology 189:203–206, 1994; JAAD 5:709–710, 1981; AD 89:222–223, 1964 Palifermin – flexural hyperpigmentation, papillomatosis, and erythema; also on elbows and knees BJD 159:1200–1203, 2008 Somatotropin-induced acanthosis nigricans BJD 141:390–391, 1999 Triazinate AD 121:232–235, 1985

INFECTIONS Tinea corporis - acanthosis nigricans-like changes

  Lipoatrophic diabetes    Familial lipodystrophy of the limbs and lower trunk (facesparing lipodystrophy) (familial partial lipodystrophy) (Kobberling-Dunnigan syndrome, Dunnigan variety) – normal at birth with onset of lipoatrophy at puberty, extreme muscularity and lack of subcutaneous fat in all extremities, excess adipose tissue of face and neck, acanthosis nigricans, mild to moderate fasting or postprandial hyperinsulinemia, impaired glucose tolerance or diabetes mellitus after age 20 years, hypertriglyceridemia/low HDL-C levels and pancreatitis J Clin Endocrinol Metab 85:1776–1782, 2000; Australas J Dermatol 39:100–105, 1998; QJM 90:27–36, 1997    Lawrence-Seip syndrome AD 91:326–334, 1965    Lipodystrophy, total AD 91:320–325, 1965;    Partial lipodystrophy Pediatrics 33:593–612, 1964  Leprechaunism AD 117:531–535, 1981  Pinealoma  Pineal hyperplasia syndrome (Rabson-Mendenhall syndrome) autosomal recessive, insulin-resistant diabetes mellitus, coarse facies, hirsutism   Hyperandrogenic states    Types A and B syndromes   Polycystic ovarian disease (Stein-Leventhal syndrome) Clin Endocrinol 30:459–464, 1989   Ovarian stromal hyperthecosis and the hyperandrogenism, insulin resistance and acanthosis nigricans syndrome J Reprod Med 40:491–494, 1995   Stromal luteoma    Ovarian dermoid cysts   Cushing’s disease  Hormone therapy - corticosteroids, oral contraceptives, estrogens, pituitary extract, insulin   Pituitary basophilism  Obesity  Hypothyroidism   Addison’s disease   Hypogonadal syndrome with insulin resistance Familial hypertrophy of the pineal body JAAD 57:502–508, 2007 Familial insulin resistance with acanthosis nigricans, acral hypertrophy, and muscle cramps Gigantism JAAD 57:502–508, 2007 Hashimoto’s thyroiditis Hemochromatosis Hyperinsulinemia Ped Derm 12:323–326, 1995

METABOLIC DISEASES Acral hypertrophy syndrome

Hyperphosphatasemia (juvenile Paget’s disease of bone) Clin Exp Dermatol 7:605–609, 1982

Acromegaly JAAD 57:502–508, 2007; JAMA 198:619–623, 1966

Hyperthyroidism JAAD 21:461–469, 1989; Hashimoto’s thyroiditis JAAD 57:502–508, 2007

Addison’s disease

Hypothyroidism JAAD 21:461–469, 1989

Cirrhosis

Insulin resistance, type A – JAMA Derm 149:875–877, 2013; acanthosis nigricans, ovarian hyperandrogenism Ped Derm 19:267–270, 2002

Cushing’s syndrome Diabetes insipidus Encephalopathy, benign JAAD 57:502–508, 2007 Endocrine associations of acanthosis nigricans   Acral hypertrophy syndrome  Acromegaly JAAD 57:502–508, 2007; JAMA 198:619–623, 1966   Insulin-resistant states    Type A syndrome    Type B syndrome   Diabetes mellitus - sign of insulin resistance Ped Derm 19:12–14, 2002; Dermatology 198:164–166, 1999; J Basic Clin Physiol Pharmacol 9:419–439, 1998

Insulin-resistant acanthosis nigricans – Type B (autoantibodies); Type C (postreceptor level); obesity Insulin-resistant diabetes mellitus with acanthosis nigricans and hypertension – autosomal recessive; severe hyperinsulinemia, amenorrhea, hirsutism; mutation in muscle-specific regulatory subunit of protein phosphatase 1 (PPAR-gamma and PP1R3A) BJD 147:1096–1011, 2002 Insulin-resistant diabetes mellitus with acanthosis nigricans – autosomal dominant, autosomal recessive; polycystic ovarian disease in some cases BJD 147:1096–1011, 2002

Acanthosis Nigricans-Like Lesions

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Lipodystrophic diabetes

PRIMARY CUTANEOUS DISEASES

Lupoid hepatitis JAAD 57:502–508, 2007

Acanthosis nigricans, benign – sporadic JAAD 31:1–19, 1994; familial (autosomal dominant) Int J Dermatol 35:126–127, 1996; J R Soc Med 87:169, 1994; BJD 133:104–108, 1995; AD 120:1351– 1354, 1984; Arch Surg 47:517–552, 1943; JAMA 53:1369–1373, 1909; International atlas of rare skin diseases. London: HK Lewis & Co; 1891. pp 1–3; pp 4–5; familial acanthosis nigricans with hyperpigmented plaques – K6507FGFR3 mutation AD 143:1153– 1156, 2007; benign generalized Ped Derm 21:277–279, 2004; Ped Derm 20:254–256, 2003; acral acanthosis nigricans (acral acanthotic anomaly) – hyperpigmentation of elbows, knees, and knuckles JAAD 5:345–346, 1981; malignant – gastrointestinal malignancies, especially gastric carcinoma BJD 141:714–716, 1999; rarely lymphoma JAAD 31:1–19, 1994; autosomal recessive acanthosis nigricans – insulin receptor mutation BJD 169:476–478, 2013

Lupoid nephritis Metabolic syndrome - personal observation Obesity JAAD 81:1037–1057, 2019; JAAD 57:502–508, 2007; J Reprod Med 32:531–536, 1987 Phenylketonuria JAAD 57:502–508, 2007 Pituitary hypogonadism JAAD 57:502–508, 2007 Polycystic ovarian disease (Stein-Leventhal syndrome) – acanthosis nigricans, acne vulgaris, hirsutism, hair loss JAAD 71:847–856, 2014; JAAD 57:502–508, 2007; NEJM 352:1223–1236, 2005; Clin Endocrinol 30:459–464, 1989; NEJM 294:739–745, 1976; Am J Obstet Gynecol 29:181–191, 1935   Differential diagnosis:   Cushing’s syndrome   Hyperprolactinemia   Hypothyroidism   Late onset congenital adrenal hyperplasia – increased 17 hydroxy-progesterone   Pregnancy   Premature ovarian failure – increased FSH, increased LH, decreased or normal estradiol   Virilizing ovarian or adrenal tumor – total testosterone >200ng/ dl; DHEAS >700 ug/dl; increased androstenedione Pregnancy BJD 146:925–927, 2002 Primary biliary cirrhosis J Gastroenterol Hepatol 11:1021–1023, 1996

Atopic dermatitis - acanthosis nigricans-like changes Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) - acanthosis nigricans-like changes Confluent and reticulated papillomatosis AD 129:961–963, 1993 Granular parakeratosis Ped Derm 20:215–220, 2003 Ichthyosis hystrix - acanthosis nigricans-like changes Transverse nasal groove Ped Derm 36:973–974, 2019 Unilateral nevoid acanthosis nigricans – may be epidermal nevus resembling acanthosis nigricans JAAD 58:S102–103, 2008; JAAD 57:502–508, 2007; Acta DV 84:234–235, 2004; Int J Dermatol 30:452–453, 1991; BJD 95:433–436, 1976

Pseudo-acanthosis nigricans Streak gonads JAAD 57:502–508, 2007 Vulvar acanthosis nigricans - marker for insulin resistance in hirsute women Fertil Steril 59:583–586, 1993 Wilson’s disease JAAD 57:502–508, 2007

SYNDROMES Acanthosis nigricans and hypochondroplasia – café au lait macules, nevi, lentigines, seborrheic keratosis; mutation in FGFR3 Ped Derm 36:242=246, 2019 Acral hypertrophy syndrome

NEOPLASTIC DISEASES Familial hyperplasia of the pineal body/pinealoma Linear epidermal nevus – acanthosis nigricans form of epidermal nevus JAAD 55:696–698, 2006; BJD 95:433–436, 1976 Lymphoma - lesions of CTCL simulating acanthosis nigricans Am J Dermatopath 7:367–371, 1985 Melanocytic nevi - giant melanocytic lesions - acanthosis nigricanslike changes Parapsoriasis en plaque Ann Dermatol Venereol 118:23–26, 1991

PARANEOPLASTIC DISORDERS Apudomas Leser-Trelat JAAD 42:357–362, 2000 Malignant acanthosis nigricans – verrucous papules at corners of mouth; cobblestoned hard palate; fissured tongue; velvety dorsal fingers; Adenocarcinoma of breast, lung, colon, esophagus, gallbladder, kidney, liver, ovary, pancreas, prostate, rectum, uterus, gastrointestinal tract Cutis 89:14–16, 2012; Int J Dermatol 43:530–532, 2004; Cancer 15:433–439, 1962; Arch Surg 47:517–552, 1943; malignant acanthosis nigricans and tripe palms; cobblestoned lips, buccal mucosa, and tongue – pancreatic carcinoma Cutis 78:37–40, 2006 Pituitary basophilism and other pituitary tumors JAAD 57:502–508, 2007 Sezary syndrome BJD 174:233–234, 2016

Adrenogenital syndrome Alstrom syndrome – retinitis pigmentosa, sensorineural deafness, obesity, diabetes mellitus BJD 164:878–880, 2011; AD 143:1153– 1156, 2007; BJD 147:1096–1011, 2002; Acta Paediatr Taiwan 41:270–272, 2000; Hum Mol Genet 6:213–219, 1997; Arch Dis Child 50:703–708, 1975 Ataxia-telangiectasia – acanthosis nigricans and hirsutism Ped Derm 28:494–501, 2011; JAAD 57:502–508, 2007; JAAD 10:431– 438, 1984 Bannayan-Riley-Ruvalcaba-Zonana syndrome (PTEN phosphatase and tensin homolog hamartoma) – dolichocephaly, frontal bossing, macrocephaly, ocular hypertelorism, long philtrum, thin upper lip, broad mouth, relative micrognathia, lipomas, penile or vulvar lentigines, facial verruca-like or acanthosis nigricans-like papules, multiple acrochordons, angiokeratomas, transverse palmar crease, accessory nipple, syndactyly, brachydactyly, vascular malformations, arteriovenous malformations, lymphangiokeratoma, goiter, hamartomatous intestinal polyposis JAAD 68:189–209, 2013; JAAD 53:639–643, 2005; AD 132:1214–1218, 1996 Bartter’s syndrome JAAD 57:502–508, 2007 Beare-Stevenson syndrome – autosomal dominant; acanthosis nigricans, cutis verticis gyrata (furrowed skin), craniosynostosis with other craniofacial anomalies; hypertelorism, swollen lips, swollen fingers, prominent eyes, ear anomalies, and anogenital anomalies, umbilical herniation with prominent umbilical stump; defect in FGFR 3 gene JAAD 57:502–508, 2007; Ped Derm 20:358–360, 2003; BJD

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147:1096–1011, 2002; Am J Med Genet 44:82–89, 1992; AD 128:1379–1386, 1992 Becker’s nevus - acanthosis nigricans-like changes Berardinelli’s (Berardinelli-Seip) syndrome – congenital generalized (total) lipodystrophy; extreme muscularity and generalized loss of body fat from birth, acanthosis nigricans, acromegalic features, umbilical hernia, hirsutism and clitoromegaly, severe fasting and postprandial hyperinsulinemia, early onset diabetes mellitus, hypertriglyceridemia; 1-acylglycerol-3-phosphate O-acyltransferase 2; seipin AD 143:1153–1156, 2007; JAAD 52:341–344, 2005; AD 139:81–83, 2003; J Clin Endocrinol Metab 85:1776–1782, 2000 Bloom’s syndrome JAAD 57:502–508, 2007 Capozucca syndrome JAAD 57:502–508, 2007 Cardio-facio-cutaneous syndrome (Noonan-like short stature syndrome) – autosomal dominant, acanthosis nigricans, xerosis/ ichthyosis, eczematous dermatitis, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, nevi, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly short scalp hair and eyebrows and lashes, hemangiomas, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects JAAD 46:161–183, 2002; Ped Derm 17:231–234, 2000; JAAD 28:815– 819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992 Chondrodystrophy with dwarfism JAAD 57:502–508, 2007 Costello syndrome – acanthosis nigricans; palmar hyperkeratosis, warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet, thick, redundant palmoplantar surfaces, hypoplastic nails, short stature, craniofacial abnormalities JAAD 57:502–508, 2007; Eur J Dermatol 11:453–457, 2001; Am J Med Genet 82:187–193, 1999; Eur J Dermatol 9:533–536, 1999; J Pediatr 133:441–448, 1998; J Med Genet 35:238–240, 1998; JAAD 32:904–907, 1995; Am J Med Genet 47:176–183, 1993; Aust Paediat J 13:114–118, 1977 Crouzon syndrome (craniofacial dysostosis) – autosomal dominant; craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, prognathism JAAD 57:502–508, 2007; BJD 147:1096–1011, 2002; Cleft Palate Craniofac J 37:78–82, 2000; J Med Genet 33:744–748, 1996;acanthosis nigricans AD 128:1378–1386, 1992; Ped Derm 13:18–21, 1996; Crouzon’s syndrome with acanthosis nigricans (CAN) – onset of acanthosis nigricans during childhood, melanocytic nevi, craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hypertelorism, anti-Mongoloid slant, posteriorly placed ears, hydrocephalus; mutation in FGFR3 Ped Derm 27:43–47, 2010; Am J med Genet 84:74, 1999   FGFR-related craniosynostoses   Apert syndrome   Beare-Stevenson syndrome   Crouzon syndrome    Crouzon syndrome with acanthosis nigricans    FGFR-2-related isolated coronal synostosis   Jackson-Weiss syndrome   Muenke syndrome   Pfeiffer syndrome Dowling-Degos syndrome (reticulated pigmented anomaly of the flexures) AD 114:1150–1157, 1978 Down’s syndrome J Eur Acad Dermatol Venereol 15:325–327, 2001 Dunnigan syndrome (familial partial lipodystrophy)- lamin A/C mutation AD 143:1153–1156, 2007; JAAD 57:502–508, 2007

Edwards syndrome Familial insulin resistance with acanthosis nigricans, acral hypertrophy, and muscle cramps Genetic Skin Disorders, Second Edition, 2010, pp.94–97 HAIR-AN syndrome (type A insulin resistance syndrome) – acne, muscular physique, alopecia (hyperandrogenism), hidradenitis suppurativa, insulin-resistance, acanthosis nigricans AD 145:492– 494, 2009; JAAD 57:502–508, 2007; AD 133:431–433, 1997; J Reprod Med 39:327–336, 1994; JAAD 31:1–19, 1994; JAAD 21:461–469, 1989; J Reprod Med 32:531–536, 1987; polycystic ovaries and signs of virilization NEJM 294:739–745, 1976 Hermansky-Pudlak syndrome - hypertrichosis of the eyebrows, and trichomegaly of the arms and legs AD 135:774–780, 1999 Hirschowitz (Groll-Hirschowitz) syndrome - nerve deafness, peripheral sensory demyelinization, loss of gastric motility, ileal and jejunal diverticulae with ulcers JAAD 57:502–508, 2007; Clin Genet 28:76–78, 1985 Hypochondrodysplasia – acanthosis nigricans, short stature, frontal bossing, high forehead, prognathism, thick lips, large broad hands Ped Derm 27:664–666, 2010 Insulin resistant diabetes mellitus, acanthosis, and hypertension peroxisome proliferator activated receptor gamma AD 143:1153– 1156, 2007; JAAD 57:502–508, 2007 Keratosis-ichthyosis-deafness syndrome (KID syndrome) - nipple lesions; flexural acanthosis nigricans-like lesions JAAD 51:377–382, 2004 Laurence-Moon-Bardet-Biedel syndrome JAAD 57:502–508, 2007; JAAD 21:461–469, 1989 Lawrence-Seip syndrome JAAD 57:502–508, 2007 Lelis syndrome – acanthosis nigricans with hypohidrosis, hypotrichosis with absent lower eyelashes, pubic and axillary hair absent, hystrix-like ichthyosis of axillae, hypodontia, furrowed tongue, hyperconvex nail dystrophy, palmoplantar keratoderma, vitiligo; facies including long narrow face with upslanting palpebral fissures, strabismus, proptosis, midface hypoplasia, perioral radial furrows and perioral hyperpigmentation, prognathism, hypodontia, furrowed tongue, high arched palate Ped Derm 33:563, 2016; Am J Med Genet 146:2155–2158, 2008; J Coll Physicians’ Surg Pak 14:626– 627, 2004; Am J Med Genet A 149:1612–1613, 2002; Am J Med Genet 113:381–384, 2002 Leprechaunism (Donohue’s syndrome) – autosomal recessive; insulin resistance with extreme hyper-insulinemia, intrauterine growth retardation, elfin facies; abnormal skin with hypertrichosis; decreased subcutaneous fat, protuberant ears, distended abdomen, large hands, feet, genitalia, gonadal cystic and pancreatic islet cell hyperplasia; mutation in insulin receptor AD 143:1153–1156, 2007; JAAD 57:502–508, 2007; BJD 147:1096–1011, 2002; J Pediatr 32:739–748, 1948 Partial congenital lipodystrophy – adipose tissue depots variably affected by lipoatrophy or lipohypertrophy, hepatosplenomegaly, cardiomyopathy, features of acromegaly or hypertriglyceridemia Ped Derm 19:267–270, 2002 Miescher’s syndrome - generalized lipodystrophy, acanthosis nigricans, hypertrichosis, insulin-resistant diabetes MORFAN syndrome - mental retardation, prenatal and postnatal overgrowth, peculiar facies, acanthosis nigricans JAAD 57:502–508, 2007; Am J Med Genet 45:525–528, 1993 Multiple endocrine neoplasia syndrome (MEN I) – angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia,

ACNEIFORM ERUPTIONS kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia; mutation in menin, a nuclear protein involved in cell cycle regulation and proliferation JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004; AD 133:853–857, 1997 Olmsted syndrome Int J Derm 36:359–360, 1997; Sem Derm 14:145–151, 1995 Prader-Willi syndrome JAAD 57:502–508, 2007; JAAD 21:461–469, 1989 Pseudoacromegaly syndrome – Type A insulin resistance syndrome with acral enlargement, muscle hypertrophy, widened teeth spacing, muscle cramps JAAD 57:502–508, 2007; Ped Derm 19:267–270, 2002 Rabson-Mendenhall syndrome – autosomal recessive; insulinresistant diabetes mellitus, growth retardation, fissured tongue, unusual facies (prominent jaw), dental precocity, hypertrichosis, acanthosis nigricans, onychauxis (thick fingernails), abdominal protuberance and phallic enlargement; mentally precocious; early dentition; and premature sexual development, pineal hyperplasia, hyperplasia of the adrenal cortex; mutation in insulin receptor AD 143:1153–1156, 2007; JAAD 57:502–508, 2007; BJD 147:1096– 1011, 2002; Ped Derm 19:267–270, 2002; Am J Clin Pathol 26:283–290, 1956 Rud’s syndrome - ichthyosis, epilepsy, mental retardation, retinitis pigmentosa JAAD 57:502–508, 2007 SADDAN syndrome – autosomal dominant; short stature, severe tibial bowing, severe achondroplasia with profound developmental delay and acanthosis nigricans BJD 147:1096–1011, 2002; Am J Med Genet 85:53–65, 1999 Sjogren-Larsson syndrome – acanthosis nigricans-like lesions Ped Derm 22:569–571, 2005; Ped Derm 20:180–182, 2003 Thanatophoric dysplasia – autosomal dominant; micromelic dwarfism; defect in FGFR3 BJD 147:1096–1011, 2002 Total congenital lipoatrophy – severe insulin resistance with Type A features, hepatosplenomegaly, cardiomyopathy, features of acromegaly, hypertriglyceridemia, or genital hypertrophy Ped Derm 19:267–270, 2002 Type B insulin resistance syndrome – acanthosis nigricans in fourth decade JAAD 57:502–508, 2007; generalized acanthosis nigricans; production of autoantibodies against the insulin receptor Cutis 86:299–302, 2010 Werner’s syndrome JAAD 57:502–508, 2007

 CIDOSIS AND RASH A IN THE NEWBORN Ped Derm 23:142–144, 2006 Mitochondrial DNA syndromes Mevalonic aciduria Epidermolytic hyperkeratosis Holocarboxylase synthetase deficiency – autosomal recessive disorder of biotin metabolism; multiple carboxylase deficiency Maple syrup urine disease – acrodermatitis enteropathica-like skin manifestations Acta Ped Taiwan 44:246–248, 2003 Pseudohypoaldosteronism – miliaria rubra-like skin rash aggravated at the time of salt-losing crisis BMJ Case Rep March 20, 2014

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ACNEIFORM ERUPTIONS  UTOIMMUNE AND DISEASES OF IMMUNE A DYSFUNCTION Chronic granulomatous disease - severe acneiform eruptions JAAD 36:899–907, 1997; X-linked chronic granulomatous disease – photosensitivity, rosacea-like lesions of face Ped Derm 3:376–379, 1986 Dermatitis herpetiformis – vesiculopustular facial eruption AD 140:353–358, 2004 Hyper-IgE syndrome – neonatal acne-like eruption; resembles eosinophilic pustular folliculitis of infancy AD 140:1119–1125, 2004; Ped Derm 1:202–206, 1984 Lupus erythematosus - systemic, discoid lupus erythematosus – follicular plugging within ear resembling comedones NEJM 269:1155– 1161, 1963; DLE resembling acne rosacea Lupus 1:222–237, 1992; umbilicated papular eruption of the back with acneiform hypertrophic follicular scars BJD 87:642–649, 1972; familial systemic lupus erythematosus with white blood cell killing defect - personal observation Pemphigus vulgaris STAT1 gain of function mutation – most common cause of chronic mucocutaneous candidiasis; demodicidosis with facial papulopustular eruptions, blepharitis, chalazion, dermatitis of the neck, nail dystrophy, congenital candidiasis Ped Derm 37:159–161, 2020

CONGENITAL LESIONS Cephalic pustulosis (neonatal acne) Int J Derm 38:128–130, 1999; AD 134:995–998, 1998 Disseminated congenital comedones Ped Derm 28:58–59, 2011  vs. Familial dyskeratotic comedones Indian J Dermatol Venereol Leprol 74:142–144, 2008; Eur J Derm 14:214–215, 2004; BJD 140:956–959, 1999 Infantile and neonatal acne Cutis 94:13–16, 2014 Toxic erythema of the newborn Transient neonatal pustular melanosis

DRUG-INDUCED Drug-induced acne   Accutane - flare of pustules  ACTH JAAD 21:1179–1181, 1989  Actinomycin D – papulopustular sterile folliculitis NEJM 281:1094–1096, 1969  Afatinib (epidermal growth factor receptor-tyrosine kinase inhibitor) – acneiform eruptions, pruritus, exerosis, paronychia JAMA Derm 152:340–342, 2016  Aminopterin Eur J Dermatol 9:491–492, 1999; Arch Derm Research 282:103–107, 1990  Ampicillin - acneiform pustular eruption of cheeks Cutis 56:163– 164, 1995   Anabolic steroids Cutis 50:113–116, 1992; Cutis 44:30–35, 1989  Androgenic hormones – in adults; infantile acne JAAD 56:S15– 18, 2007  Antiepidermal growth factor receptor antibody C225 BJD 144:1169–1176, 2001; others in this group of drugs JAAD 56:317–326, 2007; J Clin Oncol 20:2240–2250, 2002

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 Azathioprine hypersensitivity reaction – occurs within first four weeks of treatment; acneiform lesions; fever, malaise, arthralgias, myalgias, nausea, vomiting, diarrhea; morbilliform eruption, leukocytoclastic vasculitis, acute generalized exanthematous pustulosis, erythema nodosum, Sweet’s syndrome; red papulonodules with pustules JAAD 65:184–191, 2011  Bevacizumab (VEGF inhibitor) J Drugs Dermatol 1:1052–1055, 2013; AD 146:577, 2010  Bromoderma JAAD 58:682–684, 2008; AD 115:1334–1335, 1979  Cetuximab (epidermal growth factor receptor inhibitor) – rosacealike JAAD 56:317–326, 2007; JAAD 55:657–670, 2006; JAAD 55:429–437, 2006; AD 141:1173–1174, 2005; J Clin Oncol 18:904–914, 2000   Chloral hydrate  Chlorides   Chlorinated hydrocarbons  Corticosteroids – oral, inhaled, topical; acne rosacea – papules, pustules, atrophy, telangiectasia Cutis 83:198–204, 2009; JAAD 54:1–15, 2006; Clin Exp Dermatol 18:148–150, 1993; JAAD 21:1179–1181, 1989; AD Forsch 247:29–52, 1973; perianal comedones due to topical steroids JAAD 7:407, 1982; Dermatologica 119:211–220, 1959; childhood acne due to inhaled corticosteroids Ped Derm 31:712–715, 2014; desonide perioral dermatitis - personal observation; topical corticosteroid rosacea - personal observation  Cyclosporine Dermatologica 172:24–31, 1986; cysts of face in infancy AD 145:797–799, 2009  Dabrafenib – keratoacanthomas; plantar calluses, seborrheic keratosis, acneiform eruptions, epidermoid cysts, alopecia, verruca vulgaris BJD 167:1153–1160, 2012  Danazol Cutis 24:431–432, 1979  Dantrolene BJD 104:465–468, 1981 Dilantin NEJM 287:148, 1972; fetal hydantoin syndrome (childhood acne) Ped Derm 14:17–21, 1997  Disulfiram  Epidermal growth factor receptor inhibitors - cetuximab and panitumumab; erlotinib and gefitinib; lapatinib; canertinib; vandetanib JAMA Derm 153:939–940, 2017; JAAD 72:203–218, 2015; follicular papules, pustules, acneiform eruption JAAD 69:657–658, 2013; Cutis 90:77–80, 2012; JAAD 56:500–505, 2007; JAAD 56:460–465, 2007  Erlotinib (Tarceva) – epidermal growth factor receptor inhibitor acneiform eruptions, pruritus, xerosis, paronychia JAMA Derm 152:340–342, 2016; – acneiform eruption of chest JAAD 69:463–472, 2013; Clin in Dermatol 29:587–601, 2011;   AD 144:949–950, 2008; JAAD 56:317–326, 2007; JAAD 55:429–437, 2006; JAAD 54:358–360, 2006   Etanercept – cystic acne Cutis 94:31–32, 2014  Ethambutol  Ethionamide  Etretinate  Everolimus – mTOR inhibitor; broad red patches of face, scalp, upper trunk; also widespread dermatitis, acneiform eruptions The Dermatologist July 2015; pp.47–48  Gefitinib (epidermal growth factor receptor-tyrosine kinase inhibitor) – acneiform eruptions, pruritus, exerosis, paronychia JAMA Derm 152:340–342, 2016   Gemzar - rosacea  Gold Acta DV 57:165, 1977  Gonadotrophins  Granulocyte colony-stimulating factor JAAD 34:855–856, 1996; cystic acne and hidradenitis suppurativa associated with myelodysplastic syndrome AD 144:643–648, 2008  Haloperidol  Halothane

 Infliximab BJD 156:402–403, 2007  INH AD 109:377–381, 1974  Iododerma JAAD 36:1014–1016, 1997; radioactive iodine for thyroid ablation – acneiform and generalized pustular eruption J Drugs in Dermatol 9:1070–1071, 2011  IRESSA (inhibitor of epidermal growth factor receptor) – acneiform eruption of face and chest BJD 147:598–601, 2002  Levofloxacin – localized exanthematous pustulosis of forehead BJD 152:1076–1077, 2005  Lithium J Dermatol 18:481–483, 1991; BJD 106:107–109, 1982  MEK inhibitors – C1-1040, selumetinib, trametinib – morbilliform eruption, papulopustular eruptions, xerosis, paronychia Ped Derm 34:90–94, 2017; JAAD 72:221–236, 2015  Nardil  Nivolumab – lichen planus follicularis tumidus JAMA Derm 155:1197–1198, 2019  Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015  Olanzapine Cutis 66:97–100, 2000   Oral contraceptives  Panitumumab – epidermal growth factor receptor inhibitor JAAD 71:754–759, 2014; AD 146:926–927, 2010; cerebriform and acneiform eruption – associated with Demodex infection of follicles BJD 174:686–687, 2016  Phenobarbital  Phosphodiesterase 5 inhibitors (sildenafil, vardenafil, tadalafil) – facial erythema and rosacea BJD 160:719–720, 2009   Prostacycline – rosacea - personal observation   Pustular drug eruption  PUVA Br Med J ii:866, 1977  Quinidine AD 117:603–604, 1981  Quinine  Rifampicin   Selective serotonin reuptake inhibitors JAAD 56:848–853, 2007  Sirolimus (Rapamune) – acneiform eruptions of face, neck, and trunk JAAD 55:139–142, 2006  Sulfur  Tacrolimus ointment – rosacea-like dermatosis with overgrowth of Demodex folliculorum AD 140:457–460, 2004; JAAD 62:1050– 1052, 2010; focal acne AD 143:1223–1224, 2007  Thiouracil  Thiourea  Traxidone  Trimethadione  Trametinib – acneiform eruption in children with neurofibromatosis for plexiform neurofibromas; due to Demodex JAMA Derm 156:706–708, 2020  Tyrosine kinase inhibitors (second generation tyrosine kinase inhibitors in chronic myelogenous inhibitors) – dasatinib, radotinib, nilotinib BJD 174:456–458, 2016   Vemurafenib/dabrafenib – papulopustular facial rash JAAD 71:217–227, 2014   Vitamin B12 Cutis 24:119–120, 1979

EXOGENOUS AGENTS Acne cosmetica AD 106:843–850, 1972 Acne venenata (contact) – malar regions, angles of jaw, behind ears are involved; nose spared

Acneiform Eruptions   Chloracne - halogenated aromatic hydrocarbons – multiple comedones of cheeks, retroauricular areas with infrequent inflammatory lesions; chloronaphthalenes, chlorobiphenyls, chlorobiphenyl oxides used as dielectrics in conductors and insulators, chlorophenols in insecticides, fungicides, herbicides, and wood preservatives Int J Derm 35:643–645, 1996; triazoloquinoxalines BJD 161:939–943, 2009; Clin Exp Dermatol 18:523–525, 1993; Muench Med Wochenschr 46:268, 1899; organochlorine exposure (agent orange) – chloracne with comedones, gray dyschromia, hypertrichosis, folliculitis, porphyria cutanea tarda, melanoma and non-melanoma skin cancer, non-Hodgkin’s lymphoma, dermatofibrosarcoma protuberans JAAD 74:143–170, 2016   Coal tars, pitch and creosote (coal tar distillates), crude coal tar (tar acne) JAAD 39:712–720, 1998; pitch tar – periorbital comedones JAAD 42:624–627, 2000; pitch or creosote  DDT   Petroleum products (oil acne)

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nose Ped Derm 20:28–30, 2003; BJD 144:139–142, 2001; Ann DV 113:1047–1058, 1986; acneiform eruption with conjunctivitis and red face JAMA Derm 150:61–63, 2014; papular facial dermatitis in children with acute lymphoblastic leukemia Ped Derm 22:407–411, 2005; acne rosacea-like (papulopustular eruption) JAAD 60:453– 462, 2009; Gram negative folliculitis – Enterobacter aerogenes, Pseudomonas, Klebsiella pneumoniae, Proteus, Escherichia coli NEJM 352:1463– 1472, 2005; Cutis 69:261–264, 2002; AD 115:1203–1206, 1979; AD 98:349–353, 1968 Herpes simplex, including herpetic folliculitis AD 137:97–98, 2001; herpes gladiatorum Cutis 87:146–147, 2011 Herpes zoster, including comedones status-post herpes zoster AD 133:1316–1317, 1997

Asbestos

Histoplasmosis in AIDS; disseminated histoplasmosis BJD 144:205–207, 2001; AD 123:341–346, 1996; JAAD 22:1260–1269, 1990; Am J Med Sci 298:407–409, 1989; rosacea-like Int J Derm 29:649–650, 1990

Bubble gum oil – granulomatous facial eruption Acta DV (Stockh) 58:433–436, 1978

HIV disease - acne rosacea with HIV disease JAAD 30:139–140, 1994

Dental procedure – pustular contact dermatitis - personal observation

Hot tub folliculitis - personal observation

Ecstasy pimples JAAD 69:135–142, 2013

Leishmaniasis - disseminated cutaneous form Clin Dermatol 38:140–151, 2020; Ped Derm 13:455–463, 1996; post-kala azar dermal leishmaniasis – papules of cheeks, chin, ears, extensor forearms, buttocks, lower legs; in India, hypopigmented macules; nodules develop after years; tongue, palate, genitalia

Mallorca acne (tropical acne) Medicated oils – grouped comedones of infancy Neat (insoluble) cutting oils – impure paraffin-oil mixtures JAAD 30:491–492, 1994; Hautarzt 4:371, 1953 Pesticides – weed sprayer with sclerodactyly of fingers and toes with hyperkeratosis of palms and chloracne Clin Exp Dermatol 19:264–267, 1994 Pomade acne AD 110:465, 1974; AD 101:580–584, 1970 Smoker’s acne BJD 157:1070–1071, 2007 Whey – worsening acne vulgaris Cutis 90:70–72, 2012

INFECTIONS AND INFESTATIONS Acanthamebiasis – in heart transplant patient - personal observation Actinomycosis AIDS – papular dermatitis of AIDS Ascariasis Aspergillosis Bacterial cellulitis Candida - Candida folliculitis; candidal sepsis in drug addicts – purulent nodules of scalp and follicular pustules of beard, axilla, and pubis Br Med J 287:861–862, 1983; Candida parapsilosis; congenital candidiasis; rosacea-like eruption AD 142:945–946, 2006 Cercarial dermatitis (swimmer’s itch) – facial papules JAAD 60:174–176, 2009 Coccidioidomycosis – acneiform or rosacea-like papules JAAD 46:743–747, 2002 Cryptococcosis – acneiform papules and pustules around nose and mouth AD 112:1734–1740, 1976; BJD 74:43–49, 1962 Demodicidosis - Demodex folliculitis – acneiform papulopustular eruption in children Ped Derm 36:651–654, 2019; BJD 170:1219– 1225, 2014;Cutis 80:149–151, 2007; JAAD 49:S272–274, 2003; JAAD 41:775–777, 1999; JAAD 27:799–780, 1992; Ann DV 113:1047–1058, 1986; rosacea-like papules – cheeks, periorally,

Klebsiella folliculitis - personal observation

Malassezia furfura pustulosis (neonatal acne) AD 132:190–193, 1996 Maxillary sinusitis Mucormycosis Mycetoma Mycobacterium chelonae – facial lesions BJD 170:471–473, 2014; mimicking Demodex folliculitis Clin Exp Dermatol 45:469–470, 2020 Mycobacterium kansasii – rhinophyma-like lesions JAAD 41:854– 856, 1999 Mycobacterium tuberculosis – lupus vulgaris Clin Exp Dermatol 2:235–242, 1977; acne scrofulosorum - tuberculid tuberculous abscess, acute miliary tuberculosis Nocardiosis JAAD 20:889–892, 1989 Paracoccidioidomycosis JAAD 31:S91–S102, 1994 Pityrosporum folliculitis J Dermatol 27:49–51, 2000; Int J Dermatol 38:453–456, 1999; JAAD 234:693–696, 1991; Ann Int Med 108:560–563, 1988; JAAD 12:56–61, 1985 Rat bite fever (Streptobacillus moniliformis) – fever, arthritis, exanthema; papules and papulopustules of face and hand; hand and foot swellings Ped Derm 29:767–768, 2012 Rickettsial pox - personal observation Ruptured molluscum contagiosum Sporotrichosis, fixed cutaneous; rosacea-like Cutis 33:549–551, 1984 Staphylococcal folliculitis or furunculosis Swimmer’s itch - personal observation Sycosis barbae - personal observation Syphilis – secondary JAAD 82:1–145, 2020 Talaromyces (Penicillium) marneffei JAAD 54:730–732, 2006; JAAD 37:450–472, 1997

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Tinea barbae

METABOLIC DISEASES

Tinea faciei AD 114:250–252, 1978

Accelerated adrenarche – infantile acne JAAD 56:S15–18, 2007

Tinea incognito, treated with topical corticosteroids Cutis 77:293– 296, 2006; Mycoses 49:383–387, 2006 Trichodysplasia spinulosa(trichodysplasia of immunosuppression) (viral-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy) – DNA polyoma virus in renal transplant patient; alopecia, particulate matter, follicular papules, thickened skin, eyebrow alopecia, leonine facies; acneiform eruptions; inflammatory papules and pustules JID 139:255– 292, 2019; AD 148:726–733, 2012; AD 146:871–874, 2010; Ped Derm 27:509–513, 2010; JAAD 60:169–172, 2009; J Cutan Pathol 34:721–725, 2007; AD 142:1643–1648, 2006; Am J Surg Pathol 29:241–246, 2005; JAAD 52:540–541, 2005; JAAD 50:310–315, 2004; JAAD 50:318–322, 2004;JAAD 43:118–122, 2000; J Invest Dermatol Symp Proc 4:268–271, 1999; Hautarzt 46:871–874, 1995 Trichosporon beigelii sepsis - personal observation Varicella - personal observation Verrucae planae

INFILTRATIVE DISEASES Langerhans cell histiocytosis - deep painful acneiform nodules JAAD 78:1047–1056, 2018; JAAD 16:385–386, 1987 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy – acneiform red papules of face, conglobate acneiform, or red plaques with pustules JAAD 50:159–161, 2004; JAAD 41:335– 337, 1999; J Cutan Pathol 20:368–374, 1993; violaceous, red papules and nodules; cervical lymphadenopathy; also axillary, inguinal, and mediastinal adenopathy JAMA Derm 150:787–788, 2014; Cutis 87:296–299, 2011; Am J Dermatopathol 17:384–388, 1995; Cancer 30:1174–1188, 1972

INFLAMMATORY DISEASES Chronic recurrent multifocal osteomyelitis (CRMO) – seen with varied neutrophilic dermatoses including SAPHO syndrome, pyoderma gangrenosum, acne fulminans, pustular psoriasis, Sweet’s syndrome Ped Derm 26:497–505, 2009 Crohn’s disease - rosacea-like eruption JAAD 36:697–704, 1997; metastatic Crohn’s disease Ped Derm 13:25–28, 1996 Dental sinus – mimics acne cyst Eosinophilic pustular folliculitis of AIDS Ann DV 123:456–459, 1996 Eosinophilic pustular folliculitis(Ofuji’s disease) – face, trunk, upper arms; palmoplantar pustules, groups of papulopustules; annular plaques with central clearing J Dermatol 25:178–184, 1998; AD 121:917–920, 1985; eosinophilic pustular folliculitis of AIDS AD 141:1227–1231, 2005; AD 141:1203–1208, 2005; JAAD 14:1020– 1022, 1986; infantile eosinophilic pustular folliculitis Ped Derm 25:52–55, 2008 Hidradenitis suppurativa – comedones, cystic nodules, bridged scarring BJD 158:370–374, 2008; Ped Derm 24:465–473, 2007; Derm Surg 26:638–643, 2000; BJD 141:231–239, 1999; nodulocystic lesions of posterior neck and post-auricular areas AD 147:1343– 1344, 2011; association with obesity JAAD 81:1037–1057, 2019

Acrodermatitis enteropathica Acromegaly – increased susceptibility to acne Adrenal hyperactivity – hyperactive fetal adrenal during first year of life; enlarged zona reticularis secreting high levels of DHEA Dermatology 196:95–97, 1998 Adrenocortical tumors – infantile acne JAAD 56:S15–18, 2007 Androgen-producing tumors - infantile acne JAAD 56:S15–18, 2007; anovulation and hyperandrogenism JAAD 71:847–856, 2014 Aspartylglucosaminuria – acne vulgaris J Med Genet 36:398–404, 1999 Carcinoid syndrome – rosacea-like appearance BJD 152:71–75, 2005 Congenital adrenal hyperplasia – 21-hydroxylase deficiency most common; anovulation and hyperandrogenism JAAD 71:847–856, 2014; J Clin Endocrinol Metab 63:418–423, 1986 Cushing’s disease – with recurrent pituitary tumor - personal observation Cushing’s syndrome – acne and hirsutism Semin Dermatol 3:287–294, 1984; anovulation and hyperandrogenism JAAD 71:847–856, 2014 HAIR-AN syndrome – acne, muscular physique, alopecia (hyperandrogenism), hidradenitis suppurativa, insulin-­resistance, acanthosis nigricans AD 133:431–433, 1997 Necrobiosis lipoidica diabeticorum, perforating – comedone-like lesions at periphery BJD 96:83–86, 1977 Polycystic ovarian disease – acanthosis nigricans, acne vulgaris, hirsutism, hair loss JAAD 71:847–856, 2014; NEJM 352:1223– 1236, 2005; Clin Endocrinol 30:459–464, 1989; Am J Obstet Gynecol 29:181–191, 1935   Differential diagnosis:   Cushing’s syndrome   Hyperprolactinemia   Hypothyroidism   Late onset congenital adrenal hyperplasia – increased 17 hydroxy-progesterone   Pregnancy   Premature ovarian failure – increased FSH, increased LH, decreased or normal estradiol   Virilizing ovarian or adrenal tumor – total testosterone >200ng/ dl; DHEAS >700 ug/dl; increased androstenedione Precocious puberty - infantile acne JAAD 56:S15–18, 2007 Pruritic folliculitis of pregnancy – limbs and abdomen; resembles steroid-induced acne JAAD 43:132–134, 2000; Semin Derm 8:23–25, 1989; AD 117:20–22, 1981 Scurvy - exacerbation of acne JAAD 41:895–906, 1999 Transient sensitivity to circulating androgens – due to delayed maturation of gonadal inhibitory feedback system leading to transient increases in luteinizing hormone, follicle stimulating hormone and testosterone resulting in infantile acne JAAD 33:676–678, 1995; Br Med J Clin Res Ed 282:1275–1276, 1981 Zinc deficiency – papulopustular acneiform eruption - personal observation

Miliaria rubra Necrotizing infundibular crystalline folliculitis BJD 145:165–168, 2001 Neutrophilic sebaceous adenitis JAAD 55:931–932, 2019 Pyoderma gangrenosum JAAD 32:912–914, 1995 Sarcoidosis – rosacea-like lesions JAAD 44:725–743, 2001

NEOPLASTIC DISEASES Acne nevus Clin Exp Dermatol 15:154–155, 1990 Androluteoma of pregnancy - childhood acne Ped Derm 14:17–21, 1997

Acneiform Eruptions Angiosarcoma J Eur Acad Dermatol Venereol 175:574–575, 2003; rosacea-like JAAD 38:837–840, 1998 Basal cell carcinoma – pore JAAD 47:727–732, 2002 Basal cell nevus (linear basal cell nevus) – resemble comedones; usually linear translucent telangiectatic papules, may ulcerate; macular hypopigmentation, alopecia, cysts, striae Cutis 46:493– 494, 1990; BJD 74:20–23, 1962; follicular basal cell nevus – comedo-like lesions Acta DV 63:77–79, 1983 Becker’s nevus - acneiform lesions within a Becker’s nevus JAAD 10:234–238, 1984; Cutis 21:617–619, 1978 Comedo nevus of the palm (porokeratotic eccrine duct and hair follicle nevus) BJD 101:717–722, 1979 Dermoid cysts – multiple dermoid cysts of face presenting as closed comedones BJD 152:1387–1389, 2005 Dilated pore nevus – clinically resembles nevus comedonicus but has aggregated dilated follicular cysts Am J Dermatopathol 15:169–171, 1993 Eccrine nevus – dilated pore discharging mucoid secretion Arch Klin Exp Dermatol 214:600–621, 1962 Epidermal nevus – acneiform changes Ped Derm 24:534–535, 2007; BJD 96:287–290, 1977 Epidermoid cyst, ruptured – mimics acne cyst Eruptive vellus hair cysts Fibrofolliculomas resembling comedones JAAD 17:493–496, 1987 Folliculocystic and collagen hamartoma of tuberous sclerosis – pink plaque of scalp with comedones Ped Derm 31:249–250, 2014 Hydroa vacciniforme-like lymphoproliferative disorder, Epstein-Barr virus-related JAAD 81:534–540, 2019; Epstein-Barr virus-associated lymphoproliferative lesions BJD 151:372–380, 2004 Leukemia - chronic lymphocytic leukemia – transient annular erythema with pustular folliculitis BJD 150:1129–1135, 2004; chronic lymphocytic leukemic infiltrates – rosacea-like appearance BJD 150:1129–1135, 2004; Am J Surg Pathol 20:1000–1010, 1996; CLL appearing as rhinophymatous rosacea BJD 163:443, 2010 Lymphoma – pilotropic (follicular) (folliculotropic) CTCL – comedolike lesions or follicular keratotic papules; comedones, cysts, nodular prurigo, plaques JAAD 70:205–220, 2014; AD 146:607–613, 2010; JAAD 62:418–426, 2010; BJD 152:193–194, 2005; JAAD 48:448– 452, 2003; AD 138:191–198, 2002; AD 137:657–662, 2001; Ann DV 126:243–246, 1999; AD 132:683–687, 1996; cutaneous T cell lymphoma – mimicking perioral dermatitis Clin Exp Dermatol 17:132–134, 1992; poorly differentiated lymphoma – granulomatous rosacea-like facial lesions AD 122:1303–1305, 1986; lymphoplasmacytoid lymphoma (B-cell lymphoma, immunocytoma) JAAD 49:1159–1162, 2003; nasal lymphoma - rosacea-like JAAD 38:310–313, 1998; primary cutaneous follicular center lymphoma JAAD 65:887–889, 2011; B-cell lymphomas mimicking rosacea or rhinophyma AD 148:824–831, 2012; syringotropic cutaneous T-cell lymphoma – red plaques, leg ulcers, comedo-like lesions, palmoplantar hyperkeratosis JAAD 71:926–934, 2014 Lymphocytoma cutis Lymphomatoid papulosis AD 140:306–312, 2004 Melanocytic nevi Melanoma – rhinophymatous amelanotic melanoma Cutis 79:383– 386, 2007

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Munro’s acne nevus – mosaic Apert’s syndrome; inflammatory acne lesions J Dtsch Dermtol Ges 6:721–728, 2009; Lancet 352:704– 705, 1998 Nasal septal carcinoma – mimicking rosacea J Derm Surg 13:1021–1024, 1987 Nevus comedonicus NEJM 372:2541, 2015; Ped Derm 32:216–219, 2015; AD 139:93–98, 2003; AD 116:1048–1050, 1980; Trans St John’s Hosp Dermatol Soc Lond 59:45–51, 1973; with well-differentiated follicular tumors JAAD 15:1123–1127, 1986; inflammatory nevus comedonicus JAAD 38:834–836, 1998; extensive nevus comedonicus AD 116:1048–1050, 1980; with ipsilateral cataract, skeletal, and neurologic manifestations JAAD 63:1–22, 2010; AD 118:1, 1982; Int J Derm 17:745–749, 1978 Nevus corniculatus – filiform keratoses, cutaneous horns, and giant comedones BJD 122:107–112, 1990 Nevus lipomatosis superficialis – comedo-like plugs BJD 93:121– 133, 1975 Nevus tricholemmocysticus – multiple pilar cysts; filiform hyperkeratoses, comedo-like plugs, osteomalacia, bone lesions JAAD 57 (Suppl):S72–77, 2007 Pilar cyst, ruptured - mimics acne cyst Pilar sheath acanthoma - pore JAAD 47:727–732, 2002 Porokeratotic adnexal ostial nevus (cornifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic lesions with comedones; presents as red patch with red and atrophic linear and curvilinear erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAAD 61:1060–1069, 2009; BJD 103:435–441, 1980; BJD 101:717–722, 1979 Porokeratotic eccrine ostial and dermal duct nevus (linear eccrine nevus with comedones) Ped Derm 23:465–466, 2006; AD 138:1309–1314, 2002; JAAD 43:364–367, 2000; Ped Derm 15:140–142, 1998; JAAD 24:300–301, 1991; Cutis 46:495–497, 1990; BJD 101:717–722, 1979 Sebaceous hyperplasia - pore JAAD 47:727–732, 2002 Syringomas Trichilemmal cyst nevus – multiple subcutaneous nodules with cystic lesions with and without comedones in Blaschko distribution, filiform hyperkeratoses JAAD 57:S72–77, 2007 Trichilemmal cysts in a nevus comedonicus BJD 96:545–548, 1977 Trichoblastoma – with dilated pore JAAD 54:357–358, 2006 Trichodiscomas, multiple – flat-topped papules of central face JAAD 15:603–607, 1986 Trichoepitheliomas (Brooke’s tumor) - multiple – cheeks, eyelids, nasolabial folds; yellow to pink, bluish, telangiectasias on surface AD 126:953,956, 1990; J Cutan Pathol 13:111–117, 1986

PARANEOPLASTIC DISORDERS Eosinophilic pustular folliculitis associated with mantle cell lymphoma – papulopustular eruption of face Cutis 101:454–457, 2018 Sterile suppurative folliculitis associated with acute myelogenous leukemia BJD 146:904–907, 2002

Merkel cell carcinoma – rosacea-like papule J Drugs in Dermatol 9:779–784, 2010

PHOTODERMATOSES

Metastases from gastric carcinoma Cutis 52:173–176, 1993; rhinophyma-like metastatic carcinoma JAAD 34:33–36, 1996

Actinic comedonal plaque – red-blue nodular plaque with comedones Cutis 60:145–146, 1997

Multiple follicular hamartomas

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Actinic superficial folliculitis BJD 139:359–360, 1998; BJD 138:1070–1074, 1998; Clin Exp Dermatol 14:69–71, 1989; BJD 113:630–631, 1985

Galli-Galli disease – autosomal dominant; reticulated hyperpigmentation, perioral pitted scars, comedones JAMA Derm 152:461–462, 2016

Favre-Racouchot syndrome – actinic comedones JAMA Derm 151:770–774, 2015; Cutis 31:306–310, 1983; Cutis 31:296–303, 1983

Giant pore of Winer (dilated pore of Winer) JAAD 47:727–732, 2002; JID 23:181–188, 1954

PRIMARY CUTANEOUS DISEASES Acne aestivalis (Mallorca acne) Acne conglobata Hautarzt 46:417–420, 1995 Acne excoriee des jeunes filles Int J Derm 33:846–848, 1994; Clin Exp Dermatol 8:65–68, 1983 Acne fulminans (acute febrile ulcerative conglobate acne)-with myositis, polyarthralgias, inflammatory bowel disease JAAD 77:109–117, 2017; JAAD 28:572–579, 1993; Clin Rheumatol 5:118–123, 1986; AD 104:182–187, 1971

Idiopathic disseminated comedones Ped Derm 23:163–166, 2006 Infantile or juvenile acne (acne infantum) – comedones, papules, pustules, nodules, cysts, scarring Ped Derm 30:513–518, 2013; Ped Derm 25:434–438, 2008; Ped Derm 22:357–359, 2005; Cutis 52:16, 1993 Keratosis lichenoides chronica - rosacea-like JAAD 38:306–309, 1998; reticulated keratotic papules, linear arrays, atrophy, comedolike lesions, prominent telangiectasia AD 144:405–410, 2008 Keratosis pilaris rubra faciei Lichen planopilaris with cysts and comedones Clin Exp Dermatol 17:346–348, 1992

Acne keloidalis nuchae

Lupus miliaris disseminata faciei Clin Exp Dermatol 16:295–296, 1991

Acne necrotica miliaris AD 132:1365–1370, 1996

Miliaria pustulosa

Acne necrotica varioliformis AD 132:1365–1370, 1996

Perianal comedones, idiopathic AD 145:1447–1452, 2009

Acne neonatorum (neonatal cephalic pustulosis) Int J Derm 38:128–130, 1999; AD 134:995–998, 1998; due to Malassezia sympodialis AD 138:215–218, 2002

Perioral dermatitis – idiopathic or topical corticosteroid-associated granulomatous perioral dermatitis of infancy and childhood

Acne rosacea AD 134:679–683, 1998; acne agminata (granulomatous rosacea) – monomorphic brown papules of chin, cheeks, eyelids BJD 134:1098–1100, 1996; lupoid rosacea

Pityriasis lichenoides et varioliformis acuta

Acne tropicalis – pustules, cysts, and nodules of back and buttocks; sparing of face Acne vulgaris BJD 168:474–485, 2013; NEJM 352:1463–1472, 2005 Adult female cyclical acne J Drugs in Dermatol 13:126–129, 2014 Alopecia mucinosa (follicular mucinosis) JAAD 47:856–862, 2002; JAAD 38:849–851, 1998; JAAD 20:441–446, 1989 Amicrobial pustulosis – associated with systemic autoimmune disorders; scalp, axillae, ears, thighs JAAD 57:523–526, 2007; Communication no.11. Journees Dermatologiques de Paris, March 1991. Benign cephalic pustulosis (neonatal acne) JAAD 57:1012–1018, 2007 Childhood flexural comedones – double opening J Eur Acad Dermatol Venereol 23:366–367, 2009; AD 143:909–911, 2007

Pili multigemini – along jawline; with inflammatory nodules; scars Pityriasis rosea - personal observation Post-adolescent acne of the back Preadolescent acne vulgaris Ped Derm 31:27–32, 2014 Premenstrual acne Pseudoacne of transverse nasal crease JAMA Derm 151:770–774, 2015 Pseudofolliculitis barbae Pyoderma faciale (form of acne rosacea) – sudden onset of nodules, abscesses, sinuses BJD 151:917–919, 2004; AD 128:1611–1617, 1992 Rosacea fulminans - acute pustular eruption of face; pustules; red eyes BJD 163:877–879, 2010; Dermatology 188:251–254, 1994; AD 41:451–462, 1940 Transient acantholytic dermatosis (Grover’s disease) JAAD 35:653–666, 1996 Trichostasis spinulosa BJD 84:311–316, 1971

Chronic acquired dyskeratotic papulosis of the face Cutis 69:469– 471, 2002 Comedo-like acantholytic dyskeratosis of the face BJD 142:1047– 1048, 2000 Darier’s disease (keratosis follicularis) – early may be confused with acne vulgaris Clin Dermatol 19:193–205, 1994; JAAD 27:40–50, 1992; JAAD 27:40–50, 1992; comedonal Darier’s disease; nodules, cysts, ice pick scars BJD 162:687–689, 2010 Eosinophilic pustular dermatitis of infancy – acneiform pustules of chin and feet BJD 167:1189–1191, 2012 Explosive post-adolescent facial acne in women Facial Afro-Caribbean childhood eruption (FACE) – resembles perioral dermatitis Clin Exp Dermatol 15:163–166, 1990; BJD 91:435–438, 1976 Familial comedones Familial dyskeratotic comedones Eur J Dermatol 14:214–215, 2004; AD 105:249–251, 1972

PSYCHOCUTANEOUS DISEASES Anorexia nervosa - refeeding acne in anorexia nervosa Aust J Derm 31:9, 1990

SYNDROMES Acne conglobata, hidradenitis suppurativa, pili torti, and cataracts (familial) JAAD 14:207, 1986 Acne fulminans with myositis, inflammatory bowel disease, arthritis, or aseptic osteomyelitis Apert’s syndrome (acrocephalosyndactyly/ectrodactyly) – craniosynostosis, mid-facial malformations (hypoplasia), symmetrical syndactyly; a hallmark of Apert’s syndrome is an extensive often severe acneiform eruption that typically appears on the arms, chest, and back, but is relatively absent from the face; hypopigmentation

Acneiform Eruptions and hyperseborrhea; craniosynostosis, hypoplastic and retruded central face, proptosis, and short stature; mutation of fibroblast growth factor receptor-2 Ped Derm 24:186–188, 2007; Ped Derm 22:561–565, 2005; JAAD 53:173–174, 2005; Eur J Dermatol 12:496–498, 2002; Ped Derm 14:31–35, 1997; AD 128:1379–1386, 1992; Proc R Soc Med 69:517–518, 1976; AD 102:381–385, 1970; Ann Hum Genet 24:151–164, 1960; Bull Soc Med Hop (Paris) 23:1310–1330, 1906; Munro’s acne nevus – mosaic Apert’s syndrome; inflammatory acne lesions J Dtsch Dermtol Ges 6:721–728, 2009; Lancet 352:704–705, 1998 Basaloid follicular hamartoma syndrome - autosomal dominant; milia, comedone-like lesions, dermatosis papulosa nigra, skin tag-like lesions, hypotrichosis, multiple skin-colored, red, and hyperpigmented papules of the face in periorificial distribution, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes); hypohidrosis AD 144:933–938, 2008; Cutis 78:42–46, 2006; JAAD 49:698–705, 2003; BJD 146:1068–1070, 2002; JAAD 45:644–645, 2001; JAAD 43:189–206, 2000; JAAD 27:237–240, 1992 Bazex syndrome – open comedones, milia, multiple basal cell carcinomas of face, hypotrichosis, hypohidrosis, follicular atrophoderma AD 130:337–342, 1994 Becker’s nevus syndrome Am J Med Genet 68:357–361, 1997 Behcet’s disease AD 145:171–175, 2009; BJD 147:331–336, 2002; JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284– 1290, 1999; JAAD 36:689–696, 1997; JAAD 19:767–779, 1988; Behcet’s in children - erythema nodosum-like lesions, papulopustules, acneiform, folliculitis lesions, erythema multiforme-like lesions, thrombophlebitis, ulcers, abscesses, pyoderma, bullous necrotizing vasculitis, Sweet’s syndrome-like lesions Ped Derm 11:95–101, 1994; JAAD 21:327–330, 1989 Birt-Hogg-Dube syndrome - fibrofolliculomas - comedone-like lesions; mutation in FLCN gene JAMA Derm 151:770–774, 2015; BJD 162:527–537, 2010; AD 135:1195–1202, 1999 Borrone dermatocardioskeletal syndrome – autosomal recessive or X-linked; gingival hypertrophy, coarse facies, late eruption of teeth, loss of teeth, thick skin, acne conglobata, osteolysis, large joint flexion contractures, short stature, brachydactyly, camptodactyly, mitral valve prolapse, congestive heart failure Ped Derm 18:534– 536, 2001 Branchio-skeleto-genital syndrome (Elsahy-Waters syndrome) Plast Reconstr Surg 48:542–550, 1971 Carcinoid syndrome - cyanotic nose and face, rosacea JAAD 68:189–209, 2013; Acta DV (Stockh) 41:264–276, 1961 CHILD syndrome without congenital hemidysplasia – extensive lentigo simplex, linear epidermolytic nevus, and epidermolytic nevus comedonicus; mutation in KRT10 BJD 173:293–296, 2015 CRMO – chronic recurrent multifocal osteomyelitis and synovitis; acne, pustulosis, hyperostosis, osteitis; palmoplantar pustules, Sweet’s syndrome, pyoderma gangrenosum JAAD 70:767–773, 2014 Darier’s disease JAMA Derm 151:770–774, 2015; Ann Dermatol 23 (suppl 3):S398–401, 2011 Dowling-Degos syndrome mimicking chloracne – autosomal dominant; mutation in KRT5; reticulated hyperpigmentation of flexures, pitted perioral scars, comedo-like hyperkeratotic follicular papules JAAD 37:884–886, 1997; JAAD 27:345–348, 1992; comedone-like lesions on upper eyelids; comedones of neck and axilla BJD 147:568–571, 2002; AD 114:1150–1157, 1978 Ectrodactyly, ectodermal dysplasia, clefting (EEC) syndrome – nevus comedonicus Dermatologica 169:80–85, 1984

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Familial comedones Indian J Dermatol 20:6–7, 1974 Familial diffuse comedone syndrome Ped Derm 21:84–86, 2004; AD 114:1807–1809, 1978 Familial dyskeratotic comedone syndrome – face, trunk, arms, legs, penis Ped Derm 21:84–86, 2004; BJD 140:956–959, 1999; Eur J Dermatol 9:491–492, 1999; Arch Derm Research 282:103–107, 1990; JAAD 17:808–814, 1987; AD 105:249–251, 1972 Haber’s syndrome - rosacea-like acneiform eruption with erythema, telangiectasia, prominent follicles, comedones, small papules, atrophic pitted scars; with keratotic plaques of the trunk and extremities; seborrheic keratosis-like keratotic papules BJD 160:215–217, 2009; AD 103:452–455, 1971; BJD 77:1–8, 1965 Job’s syndrome Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, follicular occlusion triad, scalp cysts, nodules (trichilemmal tumors, squamous cell carcinoma), bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation JAAD 69:127–134, 2013; Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; JAAD 19:1124– 1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915 Kikuchi’s disease (histiocytic necrotizing lymphadenitis) – red papules of face, back, arms; red plaques; erythema and acneiform lesions of face; morbilliform, urticarial, and rubella-like exanthems; red or ulcerated pharynx; cervical adenopathy; associations with SLE, lymphoma, tuberculous adenitis, viral lymphadenitis, infectious mononucleosis, and drug eruptions Am J Surg Pathol 14:872–876, 1990 Masculinizing syndromes   Adrenal cancer  Choriocarcinoma   Cushing’s syndrome   Ovarian tumor   Stein-Leventhal syndrome Multiple endocrine neoplasia syndrome (MEN I) (Wermer’s syndrome) - angiofibromas of face and nose J Clin Endocrinol Metab 89:5328–5336, 2004; Endocr J 47:569–573, 2000; JAAD 42:939– 969, 2000; JAAD 41:890–892, 1999; AD 133:853–857, 1997 Nevoid basal cell carcinoma syndrome - comedones JAAD 11:98–104, 1984; AD 114:95–97, 1978; Birth Defects 8:140–148, 1971; linear nevoid basal cell carcinoma syndrome with overlying comedones Ped Derm 21:84–86, 2004 Nevus comedonicus syndrome – with ipsilateral polysyndactyly and bilateral oligodontia Ped Derm 27:377–379, 2010 PAM1 (PSTPIP1-associated myeloid related proteinemia) – autoinflammatory syndrome – acne vulgaris, pyoderma gangrenosum, thrombocytopenia, anemia, sterile osteomyelitis, sterile arthritis BJD 179:982–983, 2018 PAPA syndrome – autosomal dominant; pyoderma gangrenosum, cystic acne, aseptic arthritis; sterile abscesses at injection sites; mutation in CD2 binding protein-1 JAAD 68:834–853, 2013; Ped Derm 22:262–265, 2005; Proc Natl Acad Sci USA 100:13501– 13506, 2003; Mayo Clin Proc 72:611–615, 1997

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PAPASH (PAPA-like syndrome) (auto-inflammatory syndrome) – autosomal recessive; pyogenic arthritis, acneiform lesions; pyoderma gangrenosum, hidradenitis suppurativa, skin ulcers; mutation in proline-serine-threonine phosphatase-interacting protein 1 JAMA Derm 149: 762–763, 2013; JAMA Derm 149:209–215, 2013 PASH syndrome (pyoderma gangrenosum, acne, and hidradenitis suppurativa) BJD 176:1588–1598, 2017; JAAD 66:409–415, 2012; PSTPIP3 mutation BJD 175:194–198, 2016 Patau syndrome (trisomy 13) – comedonal and cystic acne; aplasia cutis congenita, cleft lip and/or palate, glabellar stains Ped Derm 27:199–200, 2010 Pili torti, acne conglobata, early onset cataracts BJD 91 (Suppl 10):54–57, 1974 Pseudohypoaldosteronism type I – pustular miliaria, acneiform eruptions, extensive scaling of the scalp Ped Derm 19:317–319, 2002 Pseudoxanthoma elasticum – extensive comedo formation Dermatologica 154:318–319, 1977 Pyogenic sterile arthritis, pyoderma gangrenosum, and acne – autosomal dominant; mutation in proline-serine-­threonine phosphatase interacting protein-1 (CD2-binding protein 1) JAAD 70:767–773, 2014 SAPPHO syndrome - palmoplantar pustulosis with sternoclavicular hyperostosis; acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis JAAD 68:834–853, 2013; JAAD 62:333–336, 2010; JAAD 61:123–125, 2009; Cutis 71:63–67, 2003; Curr Opinion Rheumatol 15:61–69, 2003; Cutis 64:253–258, 1999; Cutis 62:75–76, 1998; Ballieres Clin Rheumatol 8:333–362, 1994; Rev Rheum Mol Osteoarthritic 54:187–196, 1987; Ann Rev Rheum Dis 40:547–553, 1981 Steatocystoma multiplex Sweet’s syndrome JAAD 31:535–556, 1994 Tuberous sclerosis – folliculocystic and collagen hamartoma – comedo-like openings, multilobulated cysts, scalp cysts and nodules JAAD 66:617–621, 2012 47, XYY - acne conglobata AD 105:913–919, 1972

TOXINS Arsenic poisoning – at 3 months BJD 149:757–762, 2003 Chloracne – pale yellow keratin cysts and large prominent comedones on malar cheeks, post-auricular areas, ears, neck, and scrotum JAAD 13:539–558, 1985

Radiation AD 146:439–449, 2010; Hautarzt 51:187–191, 2000; AD 106:73–75, 1972; radiation-induced Favre-­Racouchot disease JAAD 49:117–119, 2003; acute or chronic radiation dermatitis – comedones JAAD 54:28–46, 2006 Radiation - acnegenic radiation dermatitis – red plaque with acneiform lesions AD 146:439–444, 2010; Br J Radiol 75:478–481, 2002 Scar - pore JAAD 47:727–732, 2002; with comedones Spinal cord injury – acne of back and buttocks BJD 112:569–573, 1985 Stump acne – a form of acne mechanica BJD 144:647–648, 2001

VASCULAR DISORDERS Angiosarcoma - rosacea-like JAAD 38:837–840, 1998; Dermatologica 181:252–254, 1990 Granulomatosis with polyangiitis – acneiform facial and truncal lesions with crusted necrotic papules, ulcers; palpable purpura JAAD 72:859–867, 2015; AD 136:171–172, 2000; mimics acne rosacea BJD 155:221–222, 2006 Hemangioma – rhinophyma J Derm Surg Oncol 19:206–212, 1993

ACRAL CYANOSIS  UTOIMMUNE AND DISEASES OF IMMUNE A DYSFUNCTION Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – loss of function mutation in cat eye syndrome chromosome candidate 1 gene (CECR1); painless leg nodules with intermittent livedo reticularis, Raynaud’s phenomenon, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae; vasculitis of small and medium arteries with necrosis, fever, early recurrent ischemic and hemorrhagic strokes, peripheral and cranial neuropathy, and gastrointestinal involvement (diarrhea); hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:199–201, 2020; NEJM 380:1582–1584, 2019; Ped Derm 33:602–614, 2016; NEJM 370:911–920, 2014; NEJM 370:921–931, 2014 Anti-phospholipid antibodies – acral necrosis of toes Cutis 100:206,209–210, 2017

Iododerma – radiocontrast material - personal observation

C1q deficiency – atrophic fingers and toes, hypopigmentation, finger tapering, butterfly rash, discoid lupus lesions, Raynaud’s phenomenon; renal disease – segmental mesangiopathic glomerulonephritis; increased interferon 1 levels Ped Derm 33:602–614, 2016

Polychlorinated biphenyl poisoning – chloracne, goiter, arthritis, and anemia Environ Health Perspect 107:715–719, 1999

Dermatomyositis with Raynaud’s phenomenon JAAD 59:633–653, 2008

Thallium - anagen effluvium JAAD 50:258–261, 2004; nausea, vomiting, stomatitis, painful glossitis, diarrhea; severe dysesthesias and paresthesias in distal extremities, facial rashes of cheeks and perioral region, acneiform eruptions of face, hyperkeratosis of palms and soles, hair loss, Mees’ lines AD 143:93–98, 2007

Hypersensitivity angiitis AD 138:1296–1298, 2002

Dioxin - late sequela JAAD 19:812–819, 1988

TRAUMA Acne mechanica – fiddler’s neck, headbands, turtle neck sweaters AD 111:481–483, 1975; comedones of thigh due to friction Ped Derm 36:546–547, 2019 Detergent acne – excessive washing AD 11:65–68, 1975

IgG4 disease – Raynaud’s phenomenon, digital gangrene, and hyperglobulinemic purpura BJD 165:1364–1366, 2011 Lupus erythematosus - systemic lupus erythematosus – Raynaud’s phenomenon JAAD 59:633–653, 2008; BJD 135:355–362, 1996; Raynaud’s phenomenon with C1q deficiency BJD 142:521–524, 2000; lupus chilblains AD 132:459–464, 1996; chilblain lupus in children Ped Derm 33:200–208, 2016; familial chilblain lupus – autosomal dominant; TREX1 mutation JAMA Derm 155:342–346, 2019 Mixed connective tissue disease – vasculitis; Raynaud’s phenomenon JAAD 59:633–653, 2008; Am J Med 52:148–159, 1972

Acral Cyanosis

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Rheumatoid arthritis, including rheumatoid vasculitis AD 135:648– 650, 1999; Raynaud’s phenomenon JAAD 59:633–653, 2008

Cetirizine - blue toes JAAD 64:1218–1219, 2011

Scleroderma, including CREST syndrome – Raynaud’s phenomenon JAAD 59:633–653, 2008

Eur Heart J 9:552–561, 1988

Sclerodermatomyositis – Gottron’s papules, periorbital erythema, Raynaud’s phenomenon, acrosteolysis, dysphagia, digital ulcers; high risk of interstitial lung disease Arthr Research Therapy 16:R111, 2014; AD 144:1351–1359, 2008; Arthr Rheum 50:565– 569, 2004; J Clin Immunol 4:40–44, 1984

Crack inhalation – acrocyanosis, necrotizing livedo reticularis (livedo racemosa), and muscle infarction Ann Int Med 108:843, 1988

Cisplatin – Raynaud’s phenomenon JAAD 59:633–653, 2008; Coumarin purple toe syndrome JAAD 61:325–332, 2009; Thromb Haemost 78:785–790, 1997; Ann Int Med 113:893–895, 1990

Cyclosporine – Raynaud’s phenomenon JAAD 59:633–653, 2008

Sjogren’s syndrome – Raynaud’s phenomenon JAAD 59:633–653, 2008; JAAD 48:311–340, 2003

d-lysergic acid amide and d-lysergamide (LSA) - blue toes JAAD 64:1218–1219, 2011

STING-associated vasculopathy with onset in infancy – red facial plaques, acral violaceous plaques and acral cyanosis, distal ulcerative lesions with infarcts, gangrene of fingers or toes, nasal septal perforation, nail dystrophy; paratracheal adenopathy,; interstitial lung disease with fibrosis; gain of function mutation in TMEM173 (stimulator of interferon genes) NEJM 371:507–518, 2014

Epinephrine Am J Emerg Med 8:46–47, 1990

CONGENITAL DISORDERS Congenital Volkmann ischemic contracture (neonatal compartment syndrome) – upper extremity circumferential contracture from wrist to elbow; necrosis, cyanosis, edema, eschar, bullae, purpura; irregular border with central white ischemic tissue with formation of bullae, edema, or spotted bluish color with necrosis, a reticulated eschar or whorled pattern with contracture of arm; differentiate from necrotizing fasciitis, congenital varicella, neonatal gangrene, aplasia cutis congenital, amniotic band syndrome, subcutaneous fat necrosis, epidermolysis bullosa BJD 150:357–363, 2004

Ergots - Raynaud’s phenomenon JAAD 59:633–653, 2008 Imipramine Arch Dis Child 63:204–205, 1988 Interferon alpha - Raynaud’s phenomenon JAAD 59:633–653, 2008 Lysergic acid diethylamide (LSD) - blue toes JAAD 64:1218–1219, 2011 Norepinephrine - blue toes JAAD 64:1218–1219, 2011 Oxymetazoline - intra-arterial injection AD 138:1296–1298, 2002 Pembrolizumab – anti-phospholipid antibody syndrome with Raynaud’s phenomenon JAMA Derm 154:1354–1356, 2018 Phenylephrine-induced microvascular occlusion syndrome – livedo racemosa, acral cyanosis and necrosis with hemorrhagic bullae AD 143:1314–1317, 2007 Propranolol – for hemangiomas Ped Derm 30:182–191, 2013; propranolol treatment of PHACES syndrome Ped Derm 30:71–89, 2013

Neonatal vasomotor instability temperature-dependent acrocyanosis; transient neonatal rubor due to vasodilatation and hyperemia, especially of the head JAAD 60:669–675, 2009

Pseudoephedrine/phenylephrine - blue toes JAAD 64:1218–1219, 2011

Spinal dysraphism

Quinine sulfate Hautarzt 51:332–335, 2000

Umbilical artery catheterization – acrocyanosis, necrosis, livedo reticularis

Tetrahydrozoline - blue toes JAAD 64:1218–1219, 2011

Psilocybine - blue toes JAAD 64:1218–1219, 2011

Vasculitis, drug-induced AD 138:1296–1298, 2002 Vinblastine - Raynaud’s phenomenon JAAD 59:633–653, 2008

DEGENERATIVE DISEASES

Warfarin - blue toes JAAD 64:1218–1219, 2011; JAAD 60:1–20, 2009

Syringomyelia – skin of fingers and knuckles becomes cyanotic, thickened, edematous, and keratotic

EXOGENOUS AGENTS DRUGS

Cannabis arteritis JAAD 58:S65–67, 2008

Acetylcholine - blue toes JAAD 64:1218–1219, 2011

Cocaine abuse – Raynaud’s phenomenon JAAD 59:483–487, 2008; Clin Rheumatol 21:343–344, 2002

Amphetamines – Raynaud’s phenomenon JAAD 59:633–653, 2008; amphetamine and methylphenidate; mixed amphetamine salts for attention deficit disorder (Adderall) – blue toes JAAD 64:1218–1219, 2011 Amphotericin B deoxycholate - blue toes JAAD 64:1218–1219, 2011 Benzocaine, topical – induced methemoglobinemia NEJM 381:1158, 2019 Beta-adrenergic blockers - Raynaud’s phenomenon JAAD 59:633– 653, 2008 Blasticidin (fungicide) Vet Hum Toxicol 38:107–112, 1996 Bleomycin – Raynaud’s phenomenon JAAD 71:203–214, 2014; JAAD 59:633–653, 2008; Clin Rheumatol 18:422–424, 1999; JAAD 33:851–852, 1995; AD 107:553–555, 1973 Buprenorphine – intra-arterial injection AD 138:1296–1298, 2002 Butyl nitrite abuse AD 135:90–91, 1999

INFECTIONS AND INFESTATIONS Capnocytophaga canimorsus – bacteremia with purpura fulminans; blue hands with generalized livedo reticularis NEJM 369:1238– 1248, 2014 Chikungunya fever, congenital – acrocyanosis Indian Pediatr 49:51–53, 2012 Covid-19 – coronavirus; chilblain-like lesions in children with mild disease Curr Rheumatol Rep 19:61, 2017 Endocarditis – subacute bacterial endocarditis Erythema induratum Hepatitis C – with cryoglobulins; thrombotic vasculitis AD 131:1185– 1193, 1995 Infectious mononucleosis Am J Med 134:159–160, 1980

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Meningococcemia Parvovirus B19 - Raynaud’s phenomenon JAAD 59:633–653, 2008 Pneumocystis carinii septicemia Ann Int Med 111:681–682, 1989 Poliomyelitis - personal observation Rubella, congenital JAAD 12:697–706, 1985 Sepsis Streptococcus pneumoniae – with DIC after splenectomy Syphilis - secondary syphilis

METABOLIC DISEASES Anti-cardiolipin and IgG cryoglobulins – leukocytoclastic vasculitis personal observation Antithrombin III deficiency - Raynaud’s phenomenon JAAD 59:633–653, 2008 Bisalbuminemia – cold, blue hands; inability to extend fingers BJD 95 (Suppl.14):54–55, 1977

Mitochondrial disorders – acrocyanosis; hypertrichosis of the back or diffusely on the back, forearms, and forehead; erythematous photodistributed eruptions followed by mottled or reticulated hyperpigmentation; alopecia with or without hair shaft abnormalities including trichothiodystrophy, trichoschisis, tiger tail pattern, pili torti, longitudinal grooving, and trichorrhexis nodosa Pediatrics 103:428– 433, 1999 Oxalosis (primary oxalosis) – autosomal recessive; livedo reticularis, acrocyanosis, peripheral gangrene, ulcerations, sclerodermoid changes (woody induration of extremities), eschar of hand (calcium oxalate); acral and/or facial papules or nodules; end stage renal disease; primary hyperoxalosis – deficiency of alanine: glyoxylate aminotransferase; primary hyperoxalosis – deficiency of D-glycerate dehydrogenase/glyoxylate reductase AD 147:1277– 1282, 2011 JAAD 49:725–728, 2003; AD 131:821–823, 1995 Paraproteinemia Raynaud’s phenomenon JAAD 59:633–653, 2008; Paroxysmal nocturnal hemoglobinuria

Cholesterol emboli - personal observation

Platelet aggregation

Cold agglutinin disease – acrocyanosis and Raynaud’s phenomenon JAAD 59:633–653, 2008; Postgrad Med 60:89–94, 1976

Polycythemia vera - Raynaud’s phenomenon JAAD 59:633–653, 2008

Cryofibrinogenemia – hands, feet, ears, nose, buttocks AD 144:405–410, 2008; Am J Med 116:332–337, 2004; Raynaud’s phenomenon JAAD 59:633–653, 2008

Protein C deficiency - Raynaud’s phenomenon JAAD 59:633–653, 2008

Cryoglobulinemia – type 1 cryoglobulinemia in multiple myeloma – acral cyanosis, Raynaud’s phenomenon; livedoid necrosis of arms, ears JAMA Derm 151:659–660, 2015; type 1 cryoglobulinemia in Waldenstrom’s macroglobulinemia or myeloma Medicine (Balt) 92:61–68, 2013; Am J Med 57:775–788, 1974; Raynaud’s phenomenon JAAD 59:633–653, 2008; acrocyanosis JAAD 48:311–340, 2003; Disseminated intravascular coagulation – obstetric complications, extensive tissue damage, pneumococcal sepsis, gram-negative septicemias, immune reactions, malignancy, snake bites, angiomas, protein S or protein C deficiency Br Med J 312:683–687, 1996; BJD 88:221–229, 1973; symmetrical peripheral gangrene (DIC) AD 121:1057–1061, 1985 Ethylmalonic aciduria and normal fatty acid oxidation J Ped 124:79–86, 1994; J Pediatr 125:843–844, 1994 Factor V Leiden mutation - Raynaud’s phenomenon JAAD 59:633– 653, 2008

Protein S deficiency - Raynaud’s phenomenon JAAD 59:633–653, 2008

NEOPLASTIC DISEASES Aortic tumors, primary Oncology 39:167–172, 1982 Atrial myxoma Cutis 62:275–280, 1998; JAAD 32:881–883, 1995; JAAD 21:1080–1084, 1989 Fibroma with pressure and occlusion Lymphoma – CTCL with ischemic foot JAAD 47:914–918, 2002; angiocentric lymphoma – Raynaud’s phenomenon BJD 142:1013– 1016, 2000 Myeloma Myeloproliferative diseases – chronic myelogenous leukemia with leukostasis; acrocyanosis as a sign AD 123:921–924, 1987

Functionally abnormal plasminogen

Pheochromocytoma

Hyperleukocytosis - acral livedo AD 123:921–924, 1987

Polycythemia vera

Hyperparathyroidism

Thrombocythemia – livedo reticularis, acrocyanosis, erythromelalgia, gangrene, pyoderma gangrenosum; essential thrombocythemia with JAK2V617F Br J Haematol 36:553–564, 1977; AD 87:302–305, 1963

Hyperviscosity JAAD 60:1–20, 2009 Interferonopathies Orphan Diseases Online J Aug 26, 2017   Aicardi-Goutieres syndrome – chilblain-like lesions  CANDLE syndrome – rash, fever, lipodystrophy, neurologic manifestations, muscular atrophy, joint contractures   Familial chilblain lupus - chilblain-like lesions   STING-associated vasculopathy (SAVI) - chilblain-like lesions  Retinal vasculopathy with cerebral leukodystrophy – blindness, cerebrovascular disease, and dementia  Spondyloenchondrolasia – neurologic disease and lupus-like symptoms  Singleton-Merten syndrome – progressive vascular calcification, osteoporosis, and osteolysis Kwashiorkor - personal observation Methylenetetrahydrofolate reductase deficiency – microcephaly and episodic cyanosis NEJM 371:847–858, 2014

Tumor emboli - melanoma AD 129:1205–1207, 1993; aortic angiosarcoma with cutaneous metastases JAAD 43:930–933, 2000 Waldenstrom’s macroglobulinemia - cryoglobulin-associated acrocyanosis, Raynaud’s phenomenon JAAD 45:S202–206, 2001

PARANEOPLASTIC DISEASES Digital ischemia Br Med J iii:208–212, 1967 Disseminated intravascular coagulation – with prostate cancer - personal observation Paraneoplastic acral vascular syndrome – acral cyanosis and gangrene JAAD 47:47–52, 2002; AD 138:1296–1298, 2002

Acral Cyanosis Paraneoplastic Raynaud’s phenomenon – neoplasms of the gastrointestinal tract, lung, breast, ovary, uterine, renal, multiple myeloma, leukemia, Hodgkin’s disease, metastatic squamous cell carcinoma; anti-cardiolipin antibodies and beta2-glycoprotein 1 IgG AD 143:1342–1343, 2007; J Clin Oncol 20:4600–4601, 2002; Clin Rheumatol 12:281–282, 1993; J Rheumatol 12:800–802, 1985 Robboy’s acral cyanosis - associated with gastric adenocarcinoma Rev Esp Enferm Apar Dig 74:562–564, 1988

PRIMARY CUTANEOUS DISEASES Erythromelalgia AD 139:1337–1343, 2003; JAAD 43:841–847, 2000; AD 136:330–336, 2000 Nodular erythrocyanosis Palmoplantar keratoderma Acta DV 75:331, 1995 Symmetrical lividity of the soles (hyperhidrosis)

PSYCHOCUTANEOUS DISEASES Anorexia nervosa Am J Clin Dermatol 6:165–173, 2005; Postgrad Med J 67:33–35, 1991

SYNDROMES Acrocyanosis – hands, feet, nose, ears, lips, nipples JAAD S207–208, 2001; Rook p.962, 1998, Sixth Edition Acrocyanosis of infancy JAAD S207–208, 2001 Aicardi-Goutieres syndrome (interferonopathy) – autosomal recessive; neurodegenerative disease; narrow facial features; chilblains, acrocyanosis, livedo reticularis, puffy hands and feet; distal tapering of fingertips; red periungual lesions; red earlobes; blueberry muffin baby; congenital progressive encephalopathy with developmental delay, ; seizures, spasticity, dystonic posturing microcephaly; basal ganglia intracranial calcification with enlarged ventricles; increased interferon alpha in blood and cerebrospinal fluid and CSF lymphocytosis; mutation in three-prime repair exonuclease 1 (TREX1;AGS1); mutation in sterile alpha motif domain and HD domain-­containing protein1 (SAMHD1;AGS5); mutation in 3 genes encoding for components of ribonuclease H2 subunit A endonuclease complex (AGS2–4); mutation in gene for RNA-specific adenosine deaminase 1 (AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1 (AGS7); Ped Derm 33:602–614, 2016; Ped Derm 26:432–435, 2009; JAAD 61:727–728, 2009; Ped Derm 26:432–435, 2009; Am J Hum Genet 81:713–725, 2007; Eur J Paediatr Neurol 69 (Suppl A):A1–A7, 2002; Ann Neurol 44:900–907, 1998 Angiokeratoma corporis diffusum (Fabry’s disease) (alpha galactosidase A deficiency) – X-linked recessive; acral areas cyanotic or blanched due to autonomic dysfunction NEJM 276:1163–1167, 1967

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Cockayne’s syndrome – acral cyanosis and edema JAMA Derm 149:1414–1418, 2013 Coffin-Lowry syndrome - loose easily stretched skin and acrocyanosis Compartment syndrome – crush injury of thorax AD 138:1296– 1298, 2002 Cornelia de Lange (Brachmann-de Lange) syndrome – generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, posterior neck, and arms, low set ears, arched palate, antimongoloid palpebrae; congenital eyelashes; xerosis, especially over hands and feet, nevi, facial cyanosis, lymphedema Ped Derm 24:421–423, 2007; JAAD 56:541–564, 2007; JAAD 48:161–179, 2003 JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993 DaCosta’s syndrome Acta DV 18:265–283, 1937 Diffuse PPK associated with acrocyanosis Down’s syndrome – short stature, cutis marmorata, acrocyanosis, low-set, small ears JAAD 46:161–183, 2002 Dyskeratosis congenita Fibroblastic rheumatism – symmetrical polyarthritis, nodules over joints and on palms, elbows, knees, ears, neck, Raynaud’s phenomenon, sclerodactyly; joint contractures, thick palmar fascia; scalp nodules, red tender swelling of toe tips, periarticular nodule; skin lesions resolve spontaneously Cutis 100:354, 356–357, 2017; JAAD 66:959–965, 2012; Ped Derm 19:532–535, 2002; AD 131:710–712, 1995 Hereditary acrolabial telangiectasia – telangiectasias, blue lips, nipples, hands, feet, elbows, knees AD 115:474–478, 1979 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) – pulmonary arteriovenous fistulae Am J Med 82:989–997, 1987 Hypereosinophilic syndrome – Raynaud’s phenomenon; acrocyanosis with superficial thrombophlebitis AD 142:1606–1610, 2006; BJD 143:641–644, 2000 Kawasaki’s disease – peripheral gangrene JAAD 69:501–510, 2013 Mitochondrial DNA syndrome Pediatrics 103:428–433, 1999; JAAD 39:819–823, 1998 POEMS syndrome – acrocyanosis, Raynaud’s phenomenon AD 146:615–623, 2010; Cutis 61:329–334, 1998 Reflex sympathetic dystrophy JAAD 35:843–845, 1996; JAAD 22:513–520, 1990; Arch Neurol 44:555–561, 1987

Antiphospholipid antibody syndrome – Raynaud’s phenomenon, acral cyanosis NEJM 346:752–763, 2002; Semin Arthritis Rheum 31:127–132, 2001; JAAD 36:149–168, 1997; JAAD 36:970–982, 1997; BJD 120:419–429, 1989

ROMBO syndrome - peripheral vasodilatation and cyanosis; vermiculate atrophoderma, milia, trichoepitheliomas Ped Derm 23:149–151, 2006; BJD 144:1215–1218, 2001; Acta DV 61: 497–503, 1981

Bazex syndrome - bulbous/violaceous fingertips; clubbing-like

Rowell’s syndrome - chilblains JAAD 21:374–377, 1989

CANDLE syndrome – acral perniotic lesions in infancy JAAD 80:291–295, 2019

Scalenus anticus syndrome (thoracic outlet) - Raynaud’s phenomenon JAAD 59:633–653, 2008

Carcinoid syndrome – cyanotic nose and face, rosacea Acta DV (Stockh) 41:264–276, 1961

Thoracic outlet obstruction Muscle Nerve 55:782–793, 2017; AD 138:1296–1298, 2002

Carpal tunnel syndrome AD 120:517–519, 1984

XXYY syndrome – features of Klinefelter’s; sparse body hair; multiple angiomas, acrocyanosis, and premature peripheral vascular disease AD 94:695–698, 1966

Cervical rib (thoracic outlet)- Raynaud’s phenomenon JAAD 59:633–653, 2008

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

TOXINS Heavy metal intoxication Methemoglobinemia Perchlorethylene (dry-cleaning) - Raynaud’s phenomenon Polyvinyl chloride exposure – Raynaud’s phenomenon Toxic oil syndrome, acute phase JAAD 18:313–324, 1988

TRAUMA Asphyxia – facial congestion, facial edema, cyanosis, periorbital or conjunctival petechiae JAAD 64811–824, 2011 Blunt trauma – repetitive blunt trauma AD 138:1296–1298, 2002 Chilblains (chronic pernio) JAAD 23:257–262, 1990; chilblains in patients with anorexia nervosa or bulimia Ped Derm 11:1–5, 1994 Crush injury AD 138:1296–1298, 2002 Electric shock AD 138:1296–1298, 2002 Frostbite - Raynaud’s phenomenon JAAD 59:633–653, 2008 Hypothenar hammer syndrome AD 138:1296–1298, 2002 Immersion foot due to ice, cold water, and fans – acral cyanosis, mottled coloration, marked edema of feet, maceration, bullae, erosions, painful ulcers, pain JAAD 69:169–171, 2013; Dermatol Clinics 17:1–17, 1999 Invasive angiography Neonatal cold injury – facial erythema or cyanosis; firm pitting edema of extremities spreads centrally; cold skin; mortality of 25% Br Med J 1:303–309, 1960 Radial or ulnar artery cannulation AD 138:1296–1298, 2002; N Y State J Med 90:375–376, 1990; radial or ulnar artery catherization Hand Surg 4:151–157, 1999 Spinal cord injury Phys Ther 70:45–49, 1990 Vibration - tools, pneumatic, typing, piano – erythrocyanosis, pain and swelling Occup Med 1:515–550, 1946; hand-arm vibration syndrome – Raynaud’s phenomenon with fingertip ulceration JAAD 59:633–653, 2008; AD 143:1343–1344, 2007; Rheumatology (Oxford) 44:587–596, 2005; J Hand Surg (Br) 26:471–474, 2001

VASCULAR DISEASES Acrocyanosis of newborn – of perioral region and palms and soles Rook p.451, 1998, Sixth Edition Aneurysmal disease - femoropopliteal arteries Angiokeratoma of Mibelli – acral dark red papules of dorsal fingers and toes of young women with recurrent chilblains and acrocyanosis AD 95:166–175, 1967 Arterial fibromuscular dysplasia AD 138:1296–1298, 2002 Arteriovenous fistulae – vascular steal syndrome in hemodialysis patients with arteriovenous fistulae Ann Dermatol Venereol 133:264–267, 2006; Curr Surg 63:130–136, 2006; AD 138:1296– 1298, 2002; acrocyanosis and/or Raynaud’s phenomenon abdominal arteriovenous fistulae – lower extremity cyanosis, pulsatile varicose veins, and scrotal edema Cutis 87:284–286, 2011 Atherosclerosis AD 138:1296–1298, 2002; Raynaud’s phenomenon JAAD 59:633–653, 2008 Buerger’s disease (thromboangiitis obliterans) - acrocyanosis and/or Raynaud’s phenomenon JAAD 59:633–653, 2008 Cutaneous collagenous vasculopathy – widespread telangiectasias, indistinguishable from generalized essential telangiectasia; telangiectatic patches of trunk and extremities; paresthesias and

Raynaud’s phenomenon JAMA Derm 149:97–102, 2013; Ped Derm 28:598–599, 2011; JAAD 63:882–885, 2010; Am J Clin Dermatol 11:63–66, 2010; Actas Dermosifiliogr 101:444–447, 2010; J Cutan Pathol 35:967–970, 2008; J Cutan Pathol 27:40–48, 2000 Cutaneous polyarteritis nodosa – atrophie blanche lesions, acrocyanosis, Raynaud’s phenomenon, peripheral gangrene, red plaques and peripheral nodules, myalgias; macular lymphocytic arteritis – red or hyperpigmented reticulated patches of legs JAAD 73:1013–1020, 2015 Embolic arterial occlusion – acrocyanosis and/or Raynaud’s phenomenon   Aneurysm of subclavian or axillary arteries  Atrial myxoma – Raynaud’s phenomenon, digital cyanosis BJD 147:379–382, 2002  Cholesterol emboli JAAD 55:786–793, 2006; BJD 146:1107– 1108, 2002; BJD 146:511–517, 2002; Medicine 74:350–358, 1995; Angiology 38:769–784, 1987; AD 122:1194–1198, 1986   Mural thrombus   Non-bacterial thrombotic (marantic) endocarditis   Paradoxic emboli   Subacute bacterial endocarditis  Thromboembolic phenomena – cardiac source, arterial source, aneurysm (subclavian or axillary arteries), infection, hypercoagulable state AD 138:1296–1298, 2002; Raynaud’s phenomenon JAAD 59:633–653, 2008 Erythrocyanosis – may have ulceration, erythema, keratosis pilaris, desquamation, nodular lesions, edema, and fibrosis Erythrocyanosis with nodules (nodular vasculitis) Glomus tumor with pressure and occlusion Granulomatosis with polyangiitis Henoch-Schonlein purpura – with antiphospholipid antibodies Arch Dis Child 86:132–133, 2002 Ischemic gangrene following shock - personal observation Hypertensive ulcer (Martorell’s ulcer) – starts as area of cyanosis with progression to ulcer of lower lateral leg with livedo at edges Phlebology 3:139–142, 1988 Peripheral digital ischemia – thrombotic microangiopathy (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome) J Invest Med 50:201–206, 2002 Peripheral vascular disease with necrosis of vein donor site - personal observation Phlegmasia cerulea dolens (venous gangrene) – massive proximal venous thrombosis resulting in arterial insufficiency; triad of asymmetric leg edema, hemorrhagic bullae, cyanosis, acral necrosis, pain NEJM 370:1742–1748, 2014; associated with HIT or as paraneoplastic phenomenon POEMS syndrome – flushing, hyperpigmentation, hypertrichosis, acrocyanosis Clin Med Res 16:16–28, 2018 Polyarteritis nodosa, including cutaneous polyarteritis nodosa acrocyanosis and/or Raynaud’s phenomenon; livedo reticularis with surrounding erythema; acrocyanosis, ulcers, peripheral gangrene, red plaques and peripheral nodules, papules, myalgias JAAD 73:1013–1020, 2015; JAAD 57:840–848, 2007; JAAD 52:1009– 1019, 2005; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014 Post-reperfusion syndrome – massive edema of muscles; may lead to amputation; peripheral cyanosis, livedo reticularis, edema

Acral Erythema and Scale With or Without Linear Cutoff of foot; myocardial injury, renal failure Int Wound J March 3, 2014; Semin Vasc Surg 22:52–57, 2009; Plast Reconstr Surg 117:1024– 1033, 2006 Pseudo-Kaposi’s sarcoma due to arterio-venous fistula AD 121:1038–1040, 1985 Purpura fulminans – disseminated intravascular coagulation (DIC); symmetric peripheral gangrene; meningococcemia, staphylococcal sepsis, Capnocytophaga canimorsus JAAD 57:944, 956, 2007; Br Med J 2:8–9, 1891 Radial artery removal for coronary bypass grafting AD 138: 1296–1298, 2002 Sneddon’s syndrome

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   Calcific vasculopathy (calciphylaxis) Impaired venous outflow   Extensive venous thrombosis    Phlegmasia cerulean dolens and venous gangrene Intravascular flow abnormalities   Paraproteinemia with hyperviscosity   Myeloproliferative disorders   Polycythemia vera   Essential thrombocythemia  Cryofibrinogenemia  Cryoglobulinemia   Cold agglutinins

Subclavian occlusive disease JAAD 10:523–525, 1984 Takayasu’s arteritis - Raynaud’s phenomenon Thrombotic thrombocytopenic purpura (TTP) Thrombotic vasculopathy - personal observation Vascular malformation Vasculitis - small, medium and large vessel; leukocytoclastic, thrombotic, granulomatous; Raynaud’s phenomenon JAAD 59:633–653, 2008 Vasospasm   Carpal tunnel syndrome  Cold  Fear   Shoulder girdle compression  Syringomyelia   Vasoconstrictors - nicotine, ergot, beta blockers Venous gangrene AD 139:1126–128, 2003; reported with heparininduced thrombocytopenia or as paraneoplastic phenomenon Venous malformations – blue toes mimicking acral cyanosis AD 144:861–867, 2008

 CRAL ERYTHEMA AND SCALE A WITH OR WITHOUT LINEAR CUTOFF  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – to essential oils (lavender, peppermint lemongrass); hand dermatitis 27:227–228, 2016 Atopic dermatitis Dermatomyositis Familial chilblain lupus – autosomal dominant; violaceous erythema and scaling of toes; ulcers, arthralgias and arthritis; mutation in SAMHD1 and TREX 1 Ped Derm 33:602–614, 2016 Graft vs. host disease, chronic – acral erythema and scaling of palms JAAD 66:515–532, 2012 Lupus erythematosus – systemic, discoid lupus erythematosus; NEJM 269:1155–1161, 1963

Venous thrombosis Blue Toe Syndrome JAAD 60:1–20, 2009

CONGENITAL LESIONS

Decreased arterial flow  Emboli   Atheroemboli    Coral reef aorta    Cardiac or aortic tumor     Myxoma     Intimal aortic angiosarcoma   Cardiac vegetations     Infective endocarditis     Nonbacterial (marantic) thrombotic endocarditis  Thrombosis   Antiphospholipid syndrome    Malignancy (paraneoplastic acral vascular syndrome)    Thrombotic thrombocytopenic purpura    Disseminated intravascular coagulation   Coumarin necrosis   Vasoconstrictive disorders   Acrocyanosis   Perniosis    Chilblain lupus erythematosus   Drug-induced vasoconstriction – amphotericin B deoxycholate, imipramine, epinephrine, systemic vasopressors, arginine vasopressin, dopamine, norepinephrine, phenylephrine, ergots   Infectious and noninfectious inflammation   Syphilis   Bacterial infection   Behcet’s disease    Other vasculitides – leukocytoclastic vasculitis   Other vascular obstruction

Vernix caseosa; normal infant

DRUG-INDUCED Acral dysesthesia syndrome, chemotherapy-induced Capecitabine – hand-foot syndrome AD 147:1418–1423, 2011 Dilantin Drug-induced photosensitivity - doxycycline Etretinate Hepatitis B vaccine – necrolytic acral erythema; psoriasiform dermatitis, acral erythema and scale, cheilitis, verrucous papules of eyelids and around nose BJD 171:1255–1256, 2014 Methotrexate photo-recall reaction

EXOGENOUS AGENTS Irritant contact dermatitis

INFECTIONS AND INFESTATIONS Candida albicans - chronic mucocutaneous candidiasis Erythrasma Hepatitis C infection - necrolytic acral erythema; red to hyperpigmented psoriasiform plaques of feet and shins with variable scale or erosions JAAD 53:247–251, 2005; Int J Derm 35:252–256, 1996

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Lymphogranuloma venereum

PRIMARY CUTANEOUS DISEASE

Scabies - personal observation Staphylococcal toxic shock syndrome NEJM 369:852, 2013

Acral necrolytic erythema – associated with hepatitis C infection AD 100:354–355, 2004; Int J Derm 35:252–256, 1996; zinc deficiency JAAD 55:S109–110, 2006;

Syphilis - primary or secondary

Apron dermatitis

Tinea manuum

Atopic dermatitis, including photoaggravated atopic dermatitis

Tinea pedis

Chronic acral dermatitis

Scarlet fever

Erythema annulare centrifugum

INFLAMMATORY DISEASES Erythema multiforme

METABOLIC Acrodermatitis enteropathica Ped Derm 25;56–59, 2008; Ped Derm 16:95–102, 1999 Carcinoid syndrome – pellagrous dermatitis (skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea BJD 152:71– 75, 2005; AD 77:86–90, 1958 Citrullinemia

Fingertip dermatitis Housewives’ dermatitis (hand dermatitis) Hyperkeratotic dermatitis of the palms BJD 109:205–208, 1983; BJD 107:195–202, 1982 Juvenile plantar dermatosis Clin Exp Dermatol 11:529–534, 1986; Semin Dermatol 1:67–75, 1982; Clin Exp Dermatol 1:253–260, 1976 Lichen planus - personal observation Necrolytic acral erythema AD 141:85–87, 2005; hepatitis C-associated necrolytic acral erythema - hyperkeratotic plaques with rim of dusky erythema Cutis 98: 16,19–20, 2016; Int J Derm 35:252–256, 2016; AD 136:755–757, 2000; Int J Derm 35:252–256, 1996 Necrolytic migratory erythema without glucagonoma JAAD 32:604–609, 1995

Cystic fibrosis – acrodermatitis enteropathica-like changes JAAD 25:896–897, 1991; AD 119:51–55, 1983

Nummular dermatitis

Essential fatty acid deficiency

Progressive symmetric erythrokeratoderma

Hartnup’s disease Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; presenting in adulthood Clin Exp Dermatol 19:407–408, 1994

Pityriasis rubra pilaris - personal observation

Maple syrup urine disease

Psoriasis - pustular psoriasis; acral pustular psoriasis associated with SLE, Sjogren’s syndrome, and Hashimoto’s thyroiditis J Dermatol 22:125–128, 1995

Multiple carboxylase deficiency

Slaughterhouse dermatitis

Pellagra AD 121:255–257, 1985 Porphyrias Propionic and methylmalonic acidemia Zinc deficiency, acquired JAAD 69:616–624, 2013; in cystic fibrosis - personal observation

SYNDROMES Bloom’s syndrome Kawasaki’s disease Kindler’s syndrome

NEOPLASTIC Lymphoma - cutaneous T-cell lymphoma; Sezary syndrome - personal observation Melanoma - amelanotic acral melanoma – JAAD 69:700–707, 2013

Netherton’s syndrome - personal observation Wiskott-Aldrich syndrome

TRAUMATIC Chilblains Sunburn

PARANEOPLASTIC DISEASES Bazex syndrome (acrokeratosis paraneoplastica) – paronychia; acral psoriasiform dermatitis with linear cutoff AD 141: 389–394, 2005; Bull Soc Fr Dermatol Syphilol 72:182, 1965

VASCULAR DISEASES Pigmented purpuric eruptions

Glucagonoma syndrome - necrolytic migratory erythema

PHOTODERMATITIS

ACRAL ERYTHEMA

Lime phototoxicity

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Photocontact dermatitis

Allergic contact dermatitis – red hands

Polymorphic light eruption

Bullous pemphigoid

Hydroa aestivale

Acral Erythema Dermatomyositis – periungual erythema JAAD 46:S159–160, 2002 Graft vs. host disease, acute - red palms and soles AD 134:602– 612, 1998; pediatric - red macules or folliculocentric papules of face, ears, palms and soles, periungual areas, upper back and neck AD 143:67–71, 2007 Lupus erythematosus - systemic lupus – characteristic erythema of dorsum of hands between knuckles; systemic lupus with erythromelalgia AD 112:688–692, 1963; subacute cutaneous LE; tumid lupus (lupus erythematosus telangiectoides) – reticulate telangiectasias of face, neck ears, hands, breasts, heels, sides of feet; punctate atrophy JAAD 41:250–253, 1999; periungual erythema JAAD 46:S159–160, 2002; red lunulae systemic lupus erythematosus with anti-phospholipid antibodies - erythema of thenar and hypothenar eminences and fingertips BJD 168:213–215, 2013; lupus vasculitis personal observation Mixed connective tissue disease Morphea Pemphigus erythematosus Rheumatoid arthritis - palmar erythema (Dawson’s palms) Scleroderma - periungual erythema JAAD 46:S159–160, 2002 Serum sickness amoxicillin - personal observation Still’s disease (juvenile rheumatoid arthritis) Urticaria

DEGENERATIVE DISEASES Peripheral neuropathy JAAD 50:456–460, 2004 Thermally-induced cutaneous vasodilatation in aging J Gerontol 48:M53–57, 1993

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Drug-induced erythema of proximal nail fold and onychodermal band due to cyclophosphamide and vincristine Cutis 52:43–44, 1993 Drug rash Eccrine squamous syringometaplasia - secondary to chemotherapy AD 133:873–878, 1997; JAAD 26:284, 1992 Erythromelalgia - calcium channel blockers (felodipine, nifedipine, amlodipine, diltiazem) JAAD 45:323–324, 2001; BJD 136:974–975, 1997 Etanercept-induced dermatomyositis – acral erythema, paronychial erythema JAMA Derm 149:1204–1208, 2013 Etoposide/teniposide/amsacrine – hand/foot syndrome JAAD 71:203–214, 2014 Everolimus – inhibitor of mTOR; used in metastatic renal ell carcinoma The Dermatologist July 2015, pp.47–48 5-fluorouracil - acral dysesthesia syndrome JAAD 58:545–570, 2008; 5-fluorouracil, capecitabine, tegafur – hand/foot syndrome JAAD 71:203–214, 2014 Fixed drug eruption – periungual and subungual erythema BJD 162:1397–1398, 2010 Hydroxyurea AD 135:818–820, 1999; AD 111:183–187, 1975; dermatomyositis-like rash JAAD 49:339–341, 2003 Imatinib – red hands and feet AD 144:1400–1402, 2008; pseudo-PCT; hemorrhagic bullae of side of hand; crusts and erythema of dorsal hands Ped Derm 31:603–607, 2014Methotrexate – acral erythema Ped Derm 24:541–546, 2007; methotrexate photo-recall Nifedipine – erythromelalgia-like erythema Br Med J 298:1252– 1253, 1989 Paclitaxel – acral dysesthesia syndrome JAAD 71:203–214, 2014

DRUG-INDUCED Acral dysesthesia syndrome (chemotherapy-induced acral erythema) (toxic erythema of chemotherapy) – intertriginous eroded plaques and acral erythema; multiple chemotherapeutic agents including cytarabine, 5-fluorouracil, taxanes (taxotere), anthracyclines, methotrexate JAAD 63:175–177, 2010; AD 133:499–504, 1997; JAAD 40:367–398, 1999; Dermatologica 148:90—92, 1974; methotrexate Ped Derm 16:398–400, 2000; polyethylene glycol-­coated liposomal doxorubicin AD 136:1475– 1480, 2000; docetaxel BJD 142:808–811, 2000; cisplatin BJD 139:750–751, 1998; etoposide Cancer Chemother Pharmacol 34:181, 1994; cytarabine JAAD 24:1023–1025, 1991; tegafur ; Acta DV 77:80–81, 1997; AD 131:364–365, 1995; 5-fluorouracil; capecitabine (Xeloda) Am J Clin Dermatol 1:225–234, 2000; sorafenib JAAD 60:299–305, 2009 Bromocriptine – erythromelalgia JAAD 43:841–847,2000 Cabozantinib – VEGFR2 inhibitor; c-met; RET multitargets; tyrosine kinase inhibitor; hand foot skin reactions with bullae, hyperkeratosis, acral erythema; skin and hair depigmentation, splinter hemorrhages, xerosis, red scrotum JAMA Derm 151:170–177, 2015

Pembrolizumab – red palms with erythema multiforme JAMA Derm 154:1057–1061, 2018 Piroxicam photodermatitis Prostacycline – continuous infusion Quinolones Therapie 51:601–602, 1996 Romiplostim (thrombopoietin agonist) – erythromelalgia BJD 161:482–484, 2009 6-mercaptopurine and mesalamine – erythrodysesthesia; red and eroded palms and soles AD 144:1079–1080, 2008 Sorafenib (multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of feet, hyperkeratotic plaque or blister of feet, red patches on pressure points, red swollen fingertips, gray blisters of fingerwebs, angular cheilitis, perianal dermatitis JAAD 71:217–227, 2014; AD 144:886–892, 2008; JAAD 58:545–570, 2008; BJD 158:592–596, 2008 Sunitinib (multikinase inhibitor) – acral erythema with hyperkeratotic plaques JAAD 71:217–227, 2014; JAAD 58:545–570, 2008 Tetracycline-induced porphyria cutanea tarda-like syndrome

Calcitonin - personal observation

Vemurafenib – toxic erythema of chemotherapy BJD 167:987–994, 2012

Calcium channel blockers – erythromelalgia JAAD 43:841–847,2000

Vincristine/vinblastine/vinorelbine – hand/foot syndrome JAAD 71:203–214, 2014

Docetaxel – acral dysesthesia syndrome JAAD 71:203–214, 2014; JAAD 58:545–570, 2008; extravasation AD 141:1326–1327, 2005 Doxorubicin/daunorubicin – hand/foot syndrome JAAD 71:203–214, 2014 Doxycycline phototoxicity; photo-onycholysis

EXOGENOUS AGENTS Contact dermatitis – capsicum (red peppers); red hands and red lips Cutis 72:21–23, 2003

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFECTIONS AND INFESTATIONS

INFLAMMATORY DISEASES

Cellulitis/erysipelas - personal observation

Erythema multiforme; Stevens-Johnson syndrome

Dengue fever (Flavivirus) – palmar erythema and edema; morbilliform or scarlatiniform eruption (classic dengue fever) – initially (first 24 hours) flushing of face, neck, and chest; morbilliform or macular eruption with white islands of sparing and petechiae; acral and/or periorbital edema, petechial mucosae, headache, fever, retroorbital pain, arthralgia, myalgia, leukopenia; absence of sore throat and cough; conjunctival hemorrhages, abdominal pain; platelet count under 240,000; incubation period 3–14 days; Aedes aegypti/A. albopictus Dermatol Clinics 29:33–38, 2011; Am J trop Med Hyg 82:922, 2010; JAAD 58:308–316, 2008; JAAD 46:430–433, 2002; Tyring, p.477, 2002; Dermatol Clinics 17:29–40, 1999; Inf Dis Clin NA 8:107, 1994; exanthem with islands of sparing (“white islands in a sea of red”) Clin Inf Dis 36:1004–1005,1074–1075, 2003; clinical differential diagnosis includes typhoid fever, leptospirosis, meningococcal disease, streptococcal disease, staph, rickettsial disease, malaria, arbovirus (chikungunya, o’nyon nyong fevers), Kawasaki’s disease

Interstitial granulomatous dermatitis - personal observation

Erysipeloid - red plaque of thumb AD 147:1456–1458, 2011

Liver disease, chronic – palmar erythema

Erythrasma

Neuropathic – alcoholic, diabetic, lepromatous

Felon

Pellagra

Fusarium solani – digital cellulitis

Polycythemia vera

Hepatitis C - periungual erythema JAAD 46:S159–160, 2002

Porphyria - congenital erythropoietic porphyria Semin Liver Dis 2:154–63, 1982

Acute HIV infection Cutis 40:171–175, 1987 Human herpesvirus 8 – relapsing inflammatory syndrome; fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, exanthem of hands, wrists, and elbows NEJM 353:156–163, 2005 Infectious eczematoid dermatitis Insect bite reaction - personal observation Janeway lesion – faint red macular lesions of thenar and hypothenar eminences NEJM 295:1500–1505, 1976

Panniculitis Toxic epidermal necrolysis

METABOLIC DISORDERS Acrodermatitis enteropathica; acquired zinc deficiency – red scaly palms and soles Cutis 81:314, 324–326, 2008 Chronic obstructive pulmonary disease (COPD) - red lunulae Cryoglobulinemia - personal observation Diabetic neuropathy - personal observation Gout - personal observation Hyperthyroidism Myxedema

Thrombocythemia – livedo reticularis, acrocyanosis, erythromelalgia, gangrene, pyoderma gangrenosum Leuk Lymphoma 22 Suppl 1:47–56, 1996; Br J Haematol 36:553–564, 1977; AD 87:302–305, 1963 Vitamin B6 (pyridoxine) deficiency – J Lab Clin Med 42:335–337, 1953;

Lepromatous leprosy

NEOPLASTIC DISORDERS

Majocchi’s granuloma

Atrial myxoma

Measles, atypical

Hodgkin’s disease - periungual erythema JAAD 46:S159–160, 2002

Parvovirus B19(erythema infectiosum) Hum Pathol 31:488–497, 2000; including papular pruritic petechial gloves and socks syndrome - hands, wrists, feet, and ankles; acral edema and erythema as initial signs BJD 151:201–206, 2004;Tyring, p.300– 301, 2002; Cutis 54:335–340, 1994; oral ulceration AD 120:891– 896, 1984

Kaposi’s sarcoma - classical or HIV-associated Metastatic gastric carcinoma JAAD 27:117–118, 1992; also breast, lung, kidney, colon (mimic felon, whitlow, paronychia)

Scarlet fever

PARANEOPLASTIC DISEASES

Pseudomonas aeruginosa – hot hand –foot syndrome (with hot tub folliculitis) JAAD 57:596–600, 2007

Bazex syndrome

Seal finger – painful, swollen red finger; synovitis J Rheumatol 13:647–648, 1986 Staphylococcal toxic shock syndrome NEJM 369:852, 2013 Syphilis - primary or secondary Tinea manuum

PHOTODERMATOSES Creosote phototoxicity Drug-induced phototoxicity

Tinea versicolor Toxic shock syndrome, either staphylococcal or streptococcal - erythema and edema of the palms and soles JAAD 39:383–398, 1998

PRIMARY CUTANEOUS DISEASES

Viral exanthem

Acral necrolytic erythema – associated with hepatitis C infection AD 100:354–355, 2004; Int J Derm 35:252–256, 1996; zinc deficiency, acquired JAAD 69:616–624, 2013; JAAD 55:S108–110, 2006

INFILTRATIVE DISEASES

Circumscribed palmar or plantar hypokeratosis – red atrophic patch JAAD 51:319–321, 2004; JAAD 49:1197–1198, 2003; JAAD 47:21–27, 2002

Mastocytosis

Acral Erythema Epidermolysis bullosa dystrophica Erythema elevatum diutinum Erythema palmare hereditarum (Lane’s disease) – red palms Ped Derm 34:590–594, 2017; Ann DV 143:32–35, 2016; JAAD 63:e46, 2010; Int J Derm 53:458–461, 2014; Case Rep Dermatol 6:245– 247, 2014; Arch Dermatol Syphilol 20:445–448, 1929 Erythrokeratolysis hiemalis (Oudsthoorn disease) (keratolytic winter erythema) – palmoplantar erythema, cyclical and centrifugal peeling of affected sites, targetoid lesions of the hands and feet – seen in South African whites; precipitated by cold weather or fever BJD 98:491–495, 1978 Familial acral erythema AD 95:483–486, 1967 Gravitational erythema Ped Derm 24:316–317, 2007; BJD 148:1267, 2003; Clin Exp Dermatol 13:259, 1988

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Hypereosinophilic syndrome – palmoplantar erythema JAAD 46:s133–136, 2002 Ichthyosis follicularis with atrichia and photophobia (IFAP) – palmoplantar erythema; collodion membrane and erythema at birth; ichthyosis, spiny (keratotic) follicular papules (generalized follicular keratoses), non-scarring alopecia, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis, photophobia; nail dystrophy, psychomotor delay, short stature; enamel dysplasia, beefy red tongue and gingiva, angular stomatitis, atopy, lamellar scales, psoriasiform plaques Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; AD 125:103–106, 1989; Ped Derm 12:195, 1995; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999 Kawasaki’s disease JAAD 39:383–398, 1998

Greither’s palmoplantar keratoderma (transgrediens et progrediens palmoplantar keratoderma) – red hands and feet; hyperkeratoses extending over Achilles tendon, backs of hands, elbows, knees; livid erythema at margins Ped Derm 20:272–275, 2003; Cutis 65:141– 145, 2000

Keratitis, ichthyosis, deafness (KID) syndrome – red hands and feet Ped Derm 23:81–83, 2006

Hand dermatitis – irritant contact dermatitis

Olmsted syndrome with erythromelalgia – palmoplantar keratoderma with erythromelalgia; mutation in transient receptor potential vanilloid 3 (TRPV3) (autosomal recessive); or membrane-bound transcription factor protease, site 2 (MBTJPS2) (X-linked recessive) BJD 171:675, 2014; JAMA Derm 150:303–306, 2014

Juvenile plantar dermatosis Lamellar ichthyosis Lichen planus Mal de Meleda – autosomal dominant, autosomal recessive transgrediens with acral erythema in glove-like distribution Dermatology 203:7–13, 2001; AD 136:1247–1252, 2000; J Dermatol 27:664–668, 2000; Dermatologica 171:30–37, 1985 Nagashima type palmoplantar keratoderma – autosomal recessive; transgradiens; acral erythema of palms and soles; hyperkeratosis of elbows and knees and ears; toenail dystrophy; mutation in SERPINB7 BJD 171:847–853, 2014; AD 144:375–379, 2008 Necrolytic migratory erythema without glucagonoma - personal observation; glucagonoma syndrome Pityriasis rubra pilaris Primary erythromelalgia – red hands; mutation in SCN9A J Med Genet 41:171–174, 2004 Progressive symmetric erythrokeratoderma Psoriasis, including pustular psoriasis Symmetrical lividity of the soles (hyperhidrosis) BJD 37:123–125, 1925 Tennis shoe dermatitis Vernix caseosa

PSYCHOCUTANEOUS DISEASES Anorexia nervosa Schweiz Med Wochenschr 22:565–575, 2000

Kindler’s syndrome Netherton’s syndrome

Red ear syndrome – may be manifestation of erythromelalgia; irritation of third cervical root; temporomandibular joint dysfunction, thalamic syndrome, headache, antiphospholipid antibody syndrome, neuropsychiatric lupus erythematosus, idiopathic; red hands and feet Ped Derm 36:686–689, 2019; Lupus 9:301–303, 2000; Neurology 47:617, 620, 1996; rare migraine variant Reflex sympathetic dystrophy (complex regional pain syndrome) JAAD 50:456–460, 2004; JAAD 22:513–520, 1990 Reactive arthritis Rombo syndrome – acral erythema, cyanotic redness, follicular atrophy (atrophoderma vermiculata), milia-like papules, telangiectasias, red ears with telangiectasia, thin eyebrows, sparse beard hair, basal cell carcinomas, short stature BJD 144:1215–1218, 2001 Schopf-Schulz-Passarge syndrome – psoriasiform plantar dermatitis (palmoplantar keratoderma); eyelid cysts (apocrine hidrocystomas), hypotrichosis, decreased number of teeth, brittle and furrowed nails AD 140:231–236, 2004; BJD 127:33–35, 1992; JAAD 10:922–925, 1984; Birth Defects XII:219–221, 1971 Scleroatrophic syndrome of Huriez - red hands and feet early in disease Ped Derm 15:207–209, 1998 Sweet’s syndrome Wells’ syndrome – red plaques of soles Cutis 72:209–212, 2003 Wiskott-Aldrich syndrome

SYNDROMES Cockayne syndrome - erythema of hands Fabry’s disease JAAD 50:456–460, 2004 Familial chilblain lupus – paronychia, acral erythema, acral papules, necrotic ulcers, facial ulcers, mutilation of fingers, ear lesions; mutation of exonuclease III domain of 3’ repair exonuclease 1 (TREX1) JAMA Derm 151:426–431, 2015 Familial Mediterranean fever - erythema and edema of the foot AD 134:929–931, 1998 Hereditary lactate dehydrogenase M-subunit deficiency – annually recurring acroerythema JAAD 27:262–263, 1992

TOXINS Acrodynia (pink disease) - mercury poisoning; acral erythema and pain, hypertension, tachycardia, mental status changes Arch Dis Child 86:453–2002; Ped Derm 21:254–259, 2004; Ann DV 121:309– 314, 1994; profuse sweating; red edematous hands and feet, hypertension, severe periumbilical pain, irritability Ped Derm 29:199–201, 2012; Pediatr Nephrol 22:903–906, 2009; Arch Dis Child 62:293–295, 1987; Lancet 29:829–830, 1948; Arch Dermatol Syphilol 26:215–237, 1932; Rev Med Fr 3:51–74, 1830 Carbon monoxide – cherry red skin

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TRAUMA Chilblains The Dermatologist June 2015: pp. 47–48 Cold erythema JAMA 180:639–42, 1962 Hair/thread tourniquet syndrome Ped Derm 19:555–556, 1988 Nerve injury, traumatic; nerve compression JAAD 50:456–460, 2004 Radiodermatitis - acute or chronic

VASCULAR DISORDERS Acquired progressive lymphangioma – brown, red, violaceous, yellow, or apple-jelly plaque; plantar red plaques JAAD 49:S250– 251, 2003 Angiodyskinesia – dependent erythema after prolonged exercise or idiopathic Surgery 61:880–890, 1967 Atherosclerosis – dependent erythema of the dorsum of the foot (Buerger’s sign) - peripheral vascular disease JAAD 50:456–460, 2004 Buerger’s disease (thromboangiitis obliterans) JAAD 50:456–460, 2004 Chilblains Congenital heart disease - personal observation Dialysis shunt-associated steal syndrome Ann Dermatol Venereol 133:264–267, 2006; Curr Surg 63:130–136, 2006; AD 138: 1296–1298, 2002 Erythromelalgia - associations include essential thrombocythemia, polycythermia vera, diabetes mellitus, peripheral neuropathy, systemic lupus erythematosus, rheumatoid arthritis, hypertension, frostbite, colon cancer, gout, calcium channel blockers, bromocriptine AD 147:309–314, 2011; AD 142:1583–1588, 2006; AD 142:283–286, 2006; BJD 153:174–177, 2005; JAAD 50:456–460, 2004; all types exacerbated by warmth; may affect one finger or toe; ischemic necrosis JAAD 22:107–111, 1990; primary (idiopathic) – lower legs, no ischemia JAAD 21:1128–1130, 1989; secondary to peripheral vascular disease JAAD 43:841–847, 2000; AD 136:330– 336, 2000; pediatric erythromelalgia – mutation in SCN9A; encodes sodium channel protein Na(v)1.7 subunit – red feet, red hands, red legs (cellulitis-like), red face, ears, nose; purple hue, cool, painful JAAD 66:416–423, 2012 Lipodermatosclerosis (hypodermatitis sclerodermiformis; sclerosing panniculitis) – chronic venous insufficiency with hyperpigmentation, induration, inflammation; champagne bottle legs Lancet ii:243–245, 1982 Pigmented purpuric eruptions Polyarteritis nodosa - cutaneous or systemic Port wine stain Primary pulmonary hypertension Vascular malformation Vasculitis - leukocytoclastic, other Venous insufficiency – stasis, acute or chronic

 CRAL PAPULES AND NODULES; A KNUCKLE PAPULES; PAPULES, DIGITAL  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Aicardi-Goutieres syndrome (interferonopathy) – autosomal recessive; neurodegenerative disease; mutation in three-prime repair exonuclease 1 (TREX1;AGS1); mutation in sterile alpha motif

domain and HD domain-­containing protein1 (SAMHD1;AGS5); mutation in 3 genes encoding for components of ribonuclease H@ subunit A endonuclease complex (AGS2–4); mutation in gene for RNA-specific adenosine deaminase 1 (AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1 (AGS7); increased interferon alpha in blood and cerebrospinal fluid and CSF lymphocytosis; chilblain-like lesions; acrocyanosis; red periungual lesions; puffy hands and feet; distal tapering of fingertips; red earlobes; livedo reticularis, blueberry muffin baby; congenital progressive encephalopathy with developmental delay; microcephaly; narrow facial features; seizures, spasticity, dystonic posturing; basal ganglia intracranial calcification with enlarged ventricles; Ped Derm 33:602–614, 2016; Ped Derm 26:432–435, 2009; JAAD 61:727–728, 2009; Ped Derm 26:432–435, 2009; Am J Hum Genet 81:713–725, 2007; Eur J Paediatr Neurol 69 (Suppl A):A1–A7, 2002; Ann Neurol 44:900–907, 1998 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis, epididymitis, cold-induced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, conjunctivitis Ped Derm 33:602–614, 2016 Chronic granulomatous disease - chilblains JAAD 36:899–907, 1997; X-linked chronic granulomatous disease – photosensitivity, chilblain lupus of fingertips and toes Ped Derm 3:376–379, 1986 Common variable immunodeficiency (Gottron-like papules) – granulomas presenting as acral skin colored or red papules and plaques with central scaling, scarring, atrophy, ulceration JAAD 73:350–352, 2015; Cutis 52:221–222, 1993 Cutaneous extravascular necrotizing granuloma (and elbow papules) JAAD 34:753–759, 1996 Dermatitis herpetiformis Dermatomyositis Curr Opin Rheum 11:475–482, 1999; tender hyperkeratotic palmar papules in palmar creases of fingers with central white coloration; palmar papules - dermatomyositis with MDA-5 (CADM-40) (melanoma differentiation-associated gene 5) MDA 5 – RNA-specific helicase; all with interstitial lung disease JAAD 78:776–785, 2018; JAAD 65:25–34, 2011 Epidermolysis bullosa acquisita - hypertrophic scars of childhood EBA JAAD 24:706–714, 1991 Graft vs. host disease, chronic JAAD 38:369–392, 1998 Hyper IgD syndrome – recurrent transient and fixed pink plaques and nodules of face and extremities; cephalic pustulosis; mevalonate kinase deficiency Ped Derm 35:482–485, 2018 Lichen planus pemphigoides – papules of dorsal hands; palmar bullae AD 146:439–444, 2010 Lupus erythematosus - acral papulonodular dermal mucinosis JAAD 27:312–315, 1992; chilblain lupus – fingers, toes, elbows, knees, calves, knuckles, nose, ears BJD 143:1050–1054, 2000; Lupus 6:122–131, 1997; BJD 98:497–506, 1978; systemic lupus – recurrent Osler’s nodes Angiology 20:33–37, 1969; anti-phospholipid antibodies with thrombotic vasculopathy; neonatal lupus erythematosus – annular plaque of sole AD 142:1351–1356, 2006; hypertrophic DLE – hyperkeratotic nodule of hand AD 145:479–484, 2009; chilblain lupus erythematosus - personal observation Pemphigoid nodularis BJD 142:143–147, 2000 Rheumatoid arthritis - rheumatoid nodule (digital papule) JAAD 11:713–723, 1984; rheumatoid papules (rheumatoid neutrophilic dermatitis) JAAD 20:348–352, 1988; rheumatoid neutrophilic dermatitis – nodules over joints AD 133:757–760, 1997; AD 125:1105–1108, 1989; violaceous papules of fingertips Cutis 78:133–136, 2006; rheumatoid nodulosis - personal observation

Acral Papules and Nodules; Knuckle Papules; Papules, Digital

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Rheumatoid vasculitis – Bywater’s lesions; purpuric papules Cutis 71:462, 464, 2003; BJD 77:207–210, 1965

Etanercept – figurate lupus erythematosus - personal observation

SAVI – STING-associated vasculopathy with onset in infancy syndrome – autosomal dominant; gain of function mutation in transmembrane protein 173 (STING) leading to chronic activation of Type I interferon pathway; violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of arms and legs violaceous scaling plaques of fingers, toes, nose, ears, cheeks; red ears which ulcerate with necrosis; progressive digital necrosis, swelling of fingers, amputation of several digits, nail loss, nail dystrophy, nasal septal perforation, severe interstitial lung disease JAAD 74:186–189, 2016; Ped Derm 33:602–614, 2016

Lenalidomide-associated Sweet’s syndrome – lesions of lateral hand AD 142:1070–1071, 2006

Scleroderma - CREST syndrome with calcinosis cutis - digital papule; knuckle hyperkeratosis in systemic scleroderma Severe combined immunodeficiency – multiple warts of hands AD 148:659–660, 2012 Adult Still’s disease – salmon colored macules and papules of dorsal hands JAAD 79:1009–1022, 2018

Imatinib-associated Sweet’s syndrome AD 141:368–370, 2005

Lichen planus-like drug reactions Methotrexate-induced rheumatoid nodulosis (acceleration MIARN) – new painful nodules of hands in chronic rheumatoid arthritis Medicine (Baltimore) 80:271–278, 2001; Arthritis Rheum 29:822– 831, 1986; Arthritis Rheum 29:822–831, 1986 Pembrolizumab – eruptive keratoacanthomas JAMA Derm 15 3:694, 2017; lichenoid papules of dorsal hand JAMA Derm 154:1057–1061, 2018 Phenytoin reaction - keratotic finger papules Cutis 61:101–102, 1998 Ranitidine (Zantac) Sorafenib – interstitial granulomatous dermatitis; red papules, nodules, and plaques of palms AD 147:1118–1119, 2011

EXOGENOUS AGENTS CONGENITAL ANOMALY

Barber’s sinus

Congenital infantile digital fibromatosis Ped Derm 19:370–371, 2002

Bullet foreign body reaction - personal observation

Congenital (infantile) pedal papules JAAD 53:333–334, 2005

Cactus spine granuloma – pink palmar distal digital papules Cutis 79:208–210, 2007; cholla cactus (genus Cylindropuntia) – painful acral papules of dorsal fingers Cutis 105:143–145, 2020

Congenital neuroblastoma, metastatic Ped Derm 37:565–567, 2020 Congenital plantar nodules - personal observation Ectopic nail with polydactyly JAAD 53:1092–1093, 2005

Catheter-related thrombus (sterile) – Janeway lesions and Osler’s nodes AD 141:1049, 2005

Precalcaneal congenital fibrolipomatous hamartoma – skin colored nodule of medial foot Ped Derm 24:74–75, 2007; of heel Ped Derm 24:339–340, 2007

Foreign body granuloma - digital papule; cactus spine (Opuntia cactus) granulomas Cutis 65:290–292, 2000; sea urchin granulomas

Supernumerary digit - digital papule Ped Derm 27:39–42, 2010; Cutis 77:365–366, 2006; Ped Derm 20:108–112, 2003

Paraffinoma – grease gun injury; nodule, plaque, sinus of hand BJD 115:379–381, 1986

DEGENERATIVE Carpal tunnel syndrome - chilblain-like lesions with necrosis Collagenous and elastotic marginal plaques of hands – thick plaques on radial aspects of second fingers and ulnar aspects of thumbs AD 147:499–504, 2011 Heberden’s nodes of knuckles - degenerative joint disease JAAD 43:892, 2000

DRUG Acral dysesthesia syndrome Azathioprine hypersensitivity reaction – occurs within first four weeks of treatment; red papules of palms; fever, malaise, arthralgias, myalgias, nausea, vomiting, diarrhea; morbilliform eruption, leukocytoclastic vasculitis, acute generalized exanthematous pustulosis, erythema nodosum, Sweet’s syndrome; red papulonodules with pustules JAAD 65:184–191, 2011 BCG vaccination Ped Derm 13:451–454, 1996 Bleomycin JAAD 33:851–852, 1995 Captopril-induced lichen planus - personal observation Cyclophosphamide – necrotizing eccrine hidradenitis JAAD 71:203–214, 2014 Dilantin – thickening of the heel pad due to long term dilantin therapy Am J Roentgenol Radium Ther Nucl Med 124:52–56, 1975

Pencil tip granuloma – graphite, clay, wax, and lacquer; blue papule of distal phalanx NEJM 366:2408, 2012 Podoconiosis – multilobulated hyperkeratotic nodules of feet; cobblestoned; bare feet exposed to red clay from alkaline volcanic rock BJD 168:550–554, 2013; JAAD 65:214–215, 2011 Silicone granulomas – firm skin colored papules of dorsum of hand after rupture of breast implants AD 147:1215–1220, 2011 Sea urchin spine – plantar nodule

INFECTIONS AND INFESTATIONS Abscesses Adenovirus - fatal disseminated adenovirus in patient with stem cell transplant – follicular papules with keratotic papules of palms and soles BJD 174:885–888, 2016 AIDS – papular mucinosis of AIDS Alternariosis – red nodule of foot Clin Inf Dis 30:13,174–175, 2000 Aspergillosis A. fumigatus in myeloma - personal observation Bartonellosis – 2–3mm papules of the dorsum of the foot Clin Inf Dis 33:772–779, 2001 Benign acral papulovesicular eruptions following smallpox vaccination (ACAM 2000); pruritic painful papulovesicular and vesiculopustular and/or bullous eruptions over extensor areas, palms and soles, dorsal hands and feet on day 10–18; generalized vaccinia AD 146:656–661, 2010 Botryomycosis – papule at base of great toe; Staphylococcus aureus JAMA Derm 153:321–322, 2017

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Bovine papular stomatitis Buruli ulcer (Mycobacteria ulcerans subspecies shinshuense) – ulcerated red nodule of hand JAMA Derm 150:64–67, 2014 Candida parapsilosis – superficial candidiasis; verrucous vegetative nodules of dorsal hands JAMA Derm 149:1431–1432, 2013 Candida - candidal sepsis, congenital candidiasis Cat scratch disease, inoculation papule Clinics in Dermatol 28:483–488, 2010; Ped Derm 5:1–9, 1988; multiple leg papules Cutis 49:318–320, 1992

1989; post kala-azar dermal leishmaniasis - digital papule; L. martiniquensis – multiple subcutaneous fibrotic; nodules of dorsal hands BJD 173:663–670, 2015; diffuse cutaneous leishmaniasis – L. aithiopica, L. Mexicana - multiple nodules of hand JAAD 73:897–908, 2015 Leprosy, lepromatous - digital papule JAAD 11:713–723, 1984 Madura foot (mycetoma) Measles – atypical measles - personal observation Milker’s nodules JAAD 49:910–911, 2003; digital papule

Caterpillar dermatitis – puss caterpillar (larval stage of flannel moth, Megalopyge opercularis) Cutis 71:445–448, 2003; Gypsy moth caterpillar vibrissae of soles

Molluscum contagiosum - painful plantar papules Cutis 90:35–41, 2012; Cutis 87:173–174, 2011; dorsal toes in AIDS Clin Dermatol 38:160–175, 2020

Cellulitis - plantar nodule Ped Derm 15:97–102, 1998

Mycetoma – eumycetoma AD 141:793–794, 2005

Chromomycosis – red papules on dorsum of hand (Chaetomium funicola); verrucous plaque BJD 157:1025–1029, 2007

Mycobacterium avium complex – plantar plaque Clin Dermatol 38:152–159, 2020; wrist nodule Clin Exp Dermatol 23:214–221, 1998

Cladosporium - personal observation Coccidioidomycosis – granuloma of foot; primary cutaneous coccidioidomycosis JAAD 49:944–949, 2003 Covid-19 – coronavirus; chilblain-like lesions in children with mild disease Curr Rheumatol Rep 19:61, 2017 Cowpox Coxsackie A16 - Gianotti-Crosti-like rash JAAD 6:862–866, 1982 Cryptococcosis (nodule) JAAD 21:167–179, 1989; cryptococcal panniculitis – nodules of lower legs and dorsal feet Cutis 85:303– 306, 2010 Cytomegalovirus Dermatophytosis, generalized Dirofilaria – hand nodule Cutis 72:269–272, 2003; Dirofilaria immitis blue papule; zoonotic deep cutaneous filariasis Ped Derm 25:230– 232, 2008 Ecthyma - personal observation Endocarditis - acute bacterial endocarditis; subacute bacterial endocarditis with Janeway lesion – faint red macular lesions of thenar and hypothenar eminences J Cut Pathol 36:1095–1098, 2009; Clin Inf Dis 32:63,149, 2001; NEJM 295:1500–1505, 1976; hemorrhagic lesions Med News 75:257–262, 1899; Osler’s node (subacute bacterial endocarditis) – small, red papules on distal finger and toe pads Austral J of Dermatol 48:251–255, 2007; Clin Inf Dis 32:63,149, 2001; JAAD 22:1088–1090, 1990; Ann Int Med 85:471–473, 1976; NEJM 295:1500–1505, 1976 Epidermodysplasia verruciformis BJD 121:463–469, 1989; Arch Dermatol Res 278:153–160, 1985; acquired epidermodysplasia verruciformis of HIV – flat topped papules of hand, forehead, scalp AD 146:903–905, 2010 Furuncle Gianotti-Crosti syndrome – Epstein-Barr virus, hepatitis B, cytomegalovirus, HHV6, Coxsackie viruses, Rotavirus, Parvovirus B 19, molluscum contagiosum, respiratory syncytial virus, parainfluenza viruses types 1,2, Bartonella henselae, Mycoplasma pneumonia, beta-hemolytic streptococcus Cutis 89:169–172, 2012; JAAD 54:136–145, 2006; Ped Derm 21:542–547, 2004; JAAD 18:239– 259, 1988; G Ital Dermatol 96:678, 1955; due to Epstein-Barr virus

Mycobacterium chelonae and fortuitum BJD 147:781–784, 2002 Mycobacterium haemophilum JAAD 59:139–142, 2008; Ped Derm 23:481–483, 2006 Mycobacterium marinum - nodule or papule of hands, elbows, knees becomes crusted ulcer or abscess; or verrucous papule; sporotrichoid; rarely widespread lesions Br Med J 300:1069–1070, 1990; AD 122:698–703, 1986; J Hyg 94:135–149, 1985; digital papule AD 142:1241–1242, 2006; Clin Inf Dis 31:439–443, 2000; crusted nodule on dorsum of hand with sporotrichoid nodules Cutis 79:33–36, 2007 Mycobacterium scrofulaceum – palmar nodule AD 138:689–694, 2002 Mycobacterium tuberculosis - papulonecrotic tuberculid – dusky red crusted or ulcerated papules occur in crops on elbows, hands, feet, knees, legs; also ears, face, buttock, and penis Cutis 75:341–346, 2005; Ped Derm 15:450–455, 1998; Int J Dermatol 30:487–490, 1991; Ped Derm 7:191–195, 1990; tuberculosis verrucosa cutis Mycobacterium xenopi Cutis 67:81–82, 2001 North American blastomycosis – verrucous nodules of toes AD 143:653–658, 2007 Orf – Parapoxvirus (genus); Family Poxviridae – red papule of finger JAMA Derm 150:1112–1113, 2014; AD 145:607–608, 2009; AD 145:321–326, 2009; Cutis 71:288–290, 2003; AD 126:235–240, 1990 Papular urticaria Paracoccidiodomycosis - exophytic verrucous nodules of feet BJD 158:624–626, 2008; paracoccidioidomycosis, disseminated (Paracoccidioides brasiliensis) – disseminated purpuric ulcerated nodules in HIV disease; ulcerated nodule of dorsal hand Clin Inf Dis 58:1431–1432,2014 Parapoxvirus from deer AD 127:79–82, 1991 Parvovirus B19 – dermatomyositis-like Gottron’s papules Hum Pathol 31:488–497, 2000 Phaeohyphomycosis (phaeohyphomycotic cyst) - subcutaneous phaeomycotic cyst - Exophiala jeanselmei Cutis 56:41–43, 1995; of finger (Exophiala) JAAD 61:977–985, 2009

Gonococcemia

Protothecosis

Hand, foot, and mouth disease - personal observation

Pseudallescheria boydii – hand nodules in pancreatic transplant patient Clin Inf Dis 64:971, 2017

Hepatitis B – papular acrodermatitis Insect bites – fleas; plantar nodule Ped Derm 15:97–102, 1998 Jelly fish envenomation - personal observation Leishmaniasis – chancre JAAD 60:897–925, 2009; acute L. major; crusted papules JAAD 51:S125–128, 2004; AD 125:1540–1542,

Pseudomonas aeruginosa – hot hand –foot syndrome (with hot tub folliculitis) JAAD 57:596–600, 2007 Rat bite fever - macular and petechial rash on palms and soles; palmar papules and pustules with necrosis; acral hemorrhagic pustules; acral morbilliform eruption with petechiae, vesicles, and

Acral Papules and Nodules; Knuckle Papules; Papules, Digital pustules; headache, migratory polyarthralgias AD 148:1411–1416, 2012; Clin Inf Dis 43:1585–1586, 1616–1617, 2006; JAAD 38:330– 332, 1998

Cutaneous mucinosis of infancy - grouped skin-colored papules resembles connective tissue nevus BJD 144:590–593, 2001; Ped Derm 18:159–161, 2001; AD 116:198–200, 1980

Rickettsial pox

Diffuse cutaneous histiocytosis

Rocky Mountain spotted fever - personal observation

Eosinophilic endomyocarditis – Janeway lesions and splinter hemorrhages JAMA Derm 151:907–908, 2015

Scabies nodule of wrist in infant Cutis 100:287–289, 2017; crusted (Norwegian); hyperkeratotic papules of knuckles; hyperkeratotic nodule of instep Ped Derm 27:93–94, 2010; hyperkeratotic nodules of the soles AD 134:1019–1024, 1998 Scedosporium apiospermum – red nodules of dorsal hand Clin Inf Dis 51:255–257, 2010 Sealpox (parapoxvirus) – gray concentric nodules with superimposed bullae BJD 152:791–793, 2005 Septic emboli JAAD 47:S263–265, 2002 Sporotrichosis Staphylococcal sepsis JAAD 47:S263–265, 2002 Syphilis – primary chancre; secondary – papulosquamous lesions of palms (acral pebbles) JAAD 82:1–145, 2020; NEJM 374:372, 2016; Clin Inf Dis 62:82–83,123–124, 2016; red plaques of soles JAAD 69:640–642, 2013; condylomata lata between toes Clin Inf Dis 55:1106,1164–1166, 2012; condyloma lata of toe webs Cutis 57:38–40, 1996; palmar red papules – congenital syphilis Ped Derm 27:308–309, 2010; Talaromyces marneffei – brown papules of fingers JAAD 49:344– 346, 2003 Tinea pedis, manuum - Trichophyton rubrum, invasive - personal observation; tinea incognito; Majocchi’s granuloma Trichosporon louberi – red papule of palm in patient with leukopenia and fever AD 147:975–980, 2011 Tularemia - digital papule Tungiasis (Tunga penetrans) (Tunga trimamillata) (toe-tip or subungual nodule) - crusted or ulcerated; interdigital eroded papule of toe JAAD 82:551–559, 2020; Clin Inf Dis 55:1227, 1273–1274, 2012; Acta Dermatovenerol (Stockh)76:495, 1996; JAAD 20:941– 944, 1989; AD 124:429–434, 1988; plantar papule JAAD 70:961– 963, 2014 Verruca vulgaris - digital papule, knuckle pads Derm Surg 27:591– 593, 2001; flat warts; plantar warts; myrmecia (deep periungual or plantar warts) BMJ 1:912–915, 1951; subungual papule JAAD 50:S45–52, 2004; toe web warts; HPV-7 BJD 162:579–586, 2010

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Fibroxanthoma Juvenile xanthogranuloma of palm Ped Derm 33:669–670, 2016; Ped Derm 13:146–147, 1996; of sole Ped Derm 15:203–206, 1998; of finger Ped Derm 23:53–55, 2006; subcutaneous nodule of heel Am J Surg Pathol 15:150–159, 1991; red plantar nodule Ped Derm 35:523–524, 2018 Langerhans cell histiocytosis – plantar nodules in infant Clin Dermatol 38:223–234, 2020 Lichen myxedematosis – resembling acral persistent papular mucinosis BJD 144:594–596, 2001; Dermatology 185:81, 1992; mimicking knuckle pads; scleromyxedema JAAD 33:37–43, 1995 Mastocytoma Ped Derm 15:386–387, 1998; knuckle pads Myxedema – palmar myxedema AD 140:121–126, 2004 Myxoma JAAD 22:343–345, 1990 Myxoid cyst JAAD 50:134–136, 2004 Recurrent self-healing cutaneous mucinosis – red papules of palms and fingertips with pustules and vesicles BJD 143:650–652, 2000 Sea blue histiocytosis – facial macular brown hyperpigmentation; nodules of face, trunk, hands, and feet; eyelid infiltration; puffy face; leonine facies JAAD 57:1031–1045, 2007 Self-healing juvenile cutaneous mucinosis - knuckle nodules JAAD 11:327–332, 1984; JAAD 31:815–816, 1994; Dermatology 189:93–94, 1994 Verruciform xanthoma of toes in patient with Milroy’s disease due to persistent leg edema Ped Derm 20:44–47, 2003; JAAD 20:313–317, 1989; disseminated verruciform xanthoma – hyperkeratotic yellow plaques; subungual pink papules Cutis 93:307–310, 2014 Xanthogranulomas - personal observation Xanthoma disseminatum JAAD 20:313–317, 1989

INFLAMMATORY DISEASES

Viral exanthem

Eccrine neutrophilic hidradenitis – due to Playstation BJD 160:892– 894, 2009

INFILTRATIVE DISEASES

Eosinophilic pustular folliculitis of infancy – plantar papules Ped Derm 21:615–616, 2004; eosinophilic folliculitis of AIDS – papules over ankles Clin Dermatol 38:160–175, 2020

Acral persistent papular mucinosis – translucent skin colored acral papules JAAD 76:S10–11, 2017; AD 143:791–796, 2007; JAAD 51:982–988, 2004; AD 122:1237–1239, 1986; mimicking knuckle pads AD 140:121–126, 2004; JAAD 27:1026–1029, 1992; focal cutaneous mucinosis - personal observation Amyloidosis – skin colored or hyperpigmented plantar papules or plaque (primary cutaneous nodular amyloid) AD 146:557–562, 2010; Cutis 59:142–144, 1997; primary cutaneous nodular amyloidosis of the toe Cutis 93:89–94, 2014; AD 139:1157–1159, 2003; primary systemic amyloidosis associated with myeloma BJD 147:602, 2002 Colloid milium Clin Exp Dermatol 18:347–350, 1993; BJD 125:80– 81, 1991 Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease) – fingertip papule Ped Derm 23:273–275, 2006; JAAD 48:S75–77, 2003; keratotic plantar papules AD 146:149–156, 2010

Erythema multiforme Medicine 68:133–140, 1989; JAAD 8:763– 765, 1983; plantar nodules Ped Derm 15:97–102, 1998 Erythema nodosum – nodules of ankles plantar erythema nodosum JAAD 26:259–260, 1992; JAAD 20:701–702, 1989 Interstitial granulomatous dermatitis - personal observation Neutrophilic dermatosis of the dorsal hands (variant of Sweet’s syndrome) JAAD 79:987–1006, 2018; AD 142:57–63, 2006 Nodular fasciitis Palisaded neutrophilic and granulomatous dermatitis – annular papules of dorsal foot BJD 159:488–489, 2008 Palmoplantar eccrine neutrophilic hidradenitis (idiopathic recurrent palmoplantar hidradenitis) (idiopathic plantar hidradenitis) Ped Derm 21:30–32, 2004; JAAD 47:S263–265, 2002; J Pediatr 160:189–191, 2001; J Pediatr 160:189–191, 2001; AD 134:76–79, 1998; Ped Derm 15:97–102, 1998; J Eur Acad Dermatovenereol 10:257–261, 1998; AD 131:817–820, 1995

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Pancreatitis with subcutaneous fat necrosis JAAD 17:359–366, 1987

fibrokeratoma Cutis 80:137–140, 2007; hyperpigmented nodule of palm Ped Derm 29:111–112, 2012

Panniculitis - plantar nodule Ped Derm 15:97–102, 1998

Acquired periungual fibrokeratoma – linear fleshy nodule emanating from proximal nail fold overlying nail JAMA Derm 150:456–457, 2014

Pyoderma gangrenosum Ped Derm 25:509–519, 2008 Recurrent idiopathic plantar eccrine hidradenitis – red nodules of soles AD 148:1357–1359, 2012 Sarcoid – nodules of hands and fingers JAMA Derm 153:681–685, 2017; fingertip nodules JAAD 44:725–743, 2001; JAAD 11:713– 723, 1984; on palmar aspects of fingers AD 132:459–464, 1996; lupus pernio JAAD 16:534–540, 1987; BJD 112:315–322, 1985

METABOLIC DISEASES Alport’s syndrome with gouty tophi, nephritis, and deafness - personal observation

Acquired reactive digital fibroma – subungual tumor with enlarged paronychium and macrodactyly JAAD 69:603–608, 2013   Differential diagnosis   Fibro-osseous pseudotumor of the digits; myofibroblastic proliferation in females; affects flexor digits and palms Chir Main 28:107–112, 2009; Cancer 58:2103–2109, 1986   Superficial acral fibromyxoma – subungual tumor Am J Surg Pathol 36:789–798, 2012   Cellular digital fibromas – resemble acquired digital fibrokeratoma and superficial acral fibromyxoma JAAD 69:603–608, 2013

Calcinosis cutis - digital papules Cutis 66:465–467, 2000; milia-like calcinosis cutis on dorsal hands in Down’s syndrome Ped Derm 19:271–273, 2002; tumoral calcinosis - acral papules and nodules; metastatic calcification in chronic renal failure - personal observation

Acral calcified vascular leiomyoma – swollen fingertip; plantar or heel nodule JAAD 59:1000–1004, 2008

Calcium oxalate Am J Kid Dis 25:492–497, 1995; secondary oxalosis – papules on palmar skin of fingers JAAD 31:368–372, 1994; cutaneous oxalate granuloma JAAD 22:316–318, 1990

Actinic keratoses; in transplant patients JAAD 47:1–17, 2002

Cerebrotendinous xanthomatosis Cholesterol crystals (subcutaneous) J Rheumatol 18:743–745, 1991 Dyslipoprotein E2 homozygous familial dysbetalipoproteinemia – xanthomas; yellow/red palmar nodules JAMA Derm 152:1275–1276, 2016 Erythropoietic protoporphyria (EPP) in the adult - plaques on dorsum of hand JAMA Derm 153:221–222, 2017; AD 121:1309– 1312, 1985 Gout - tophus - digital papule (s) Cutis 64:233–236, 1999; AD 134:499–504, 1998; microtophi in lung transplant patient - personal observation Osteoclastic activity due to tertiary hyperparathyroidism – brown tumor of fingertip Annual Meeting AAD 2000 Oxalosis (primary oxalosis) – autosomal recessive; livedo reticularis, acrocyanosis, peripheral gangrene, ulcerations, sclerodermoid changes (woody induration of extremities), eschar of hand (calcium oxalate); acral and/or facial papules or nodules; end stage renal disease; primary hyperoxalosis – deficiency of alanine: glyoxylate aminotransferase; primary hyperoxalosis – deficiency of D-glycerate dehydrogenase/glyoxylate reductase AD 147:1277– 1282, 2011 Pretibial myxedema (thyroid acropachy) Pseudohypoparathyroidism - periarticular calcified nodules JAAD 15:353–356, 1986 Sitosterolemia and xanthomatosis Verruciform xanthoma, disseminated BJD 151:717–719, 2004; papules of feet JAAD 17:695–698, 1987

Acral mucinous fibrokeratoma JAAD 50:134–136, 2004 Acral myxo-inflammatory fibroblastic sarcoma BJD 159:1315–1321, 2008 Aggressive digital papillary eccrine adenocarcinoma – occur on fingers and toes; paronychial skin colored nodule JAAD 77:549– 558, 2017; AD 146:191–196, 2010; JAAD 60:331–339, 2009; AD 145:1183–1188, 2009; Cutis 72:145–147, 2003; Dermatol Surg 26:580–583, 2000; Am J Surg Pathol 24:775–784, 2000; JAAD 23:331–334, 1990; J Cutan Pathol 14:129–146, 1987; exophytic friable multilobulated tumor JAAD 60:331–339, 2009 Aggressive digital papillary adenoma (this is now thought to be aggressive digital papillary adenocarcinoma) Cutis 69:179–182, 2002; AD 120:1612, 1984 Aggressive infantile fibromatosis AD 107:574–579, 1973 Alveolar rhabdomyosarcoma Ped Derm 12:343–347, 1995 Angioleiomyoma - pink nodule of heel Cutis 81:123,140–141, 2008 Angiolipoleiomyoma JAAD 23:1093–1098, 1990; ears, fingers, and toes JAAD 38:147–175, 1998 Apocrine hidrocystoma of fingertip BJD 152:379–380, 2005 Aponeurotic fibroma AD 107:574–579, 1973 Atrial myxoma - acral red papules with claudication JAAD 32:881–883, 1995; tender red fingertip papule JAAD 21:1080– 1084, 1989 Atypical fibroxanthoma Cancer 31:1541–1552, 1973 Basal cell carcinoma - including palmar basal cell carcinoma JAAD 33:823–824, 1995; palmar basal cell carcinoma in nevoid basal cell carcinoma syndrome AD 143:813–814, 2007; periungual – basal cell carcinoma of toenail unit JAAD 48:277–278, 2003 Blue nevus - hypopigmented blue nevus of dorsum of foot; pink papule AD 138:1091–1096, 2002; J Cutan Pathol 24:494–498, 1997; of nail fold Bony exostosis - personal observation

Xanthomas - xanthomas with lymphedema - acral plaques JAAD 36:631–633, 1997; tendinous xanthomas JAAD 13:1–30, 1985;

Bowen’s disease AD 129:1045–1048, 1995; brown hyperkeratotic papule of sole BJD 152:120–123, 2005

tuberous xanthomas JAAD 11:713–723, 1984

Calcifying aponeurotic fibroma Cancer 26:857, 1970

NEOPLASTIC DISEASE Acquired digital fibrokeratoma - digital papule Cutis 79:129–132, 2007; AD 124:1559–1564, 1988; JAAD 12:816–821, 1985; of the nail bed Dermatology 190:169–171, 1995; acquired periungual

Chondroblastoma, subungual – toe tip Ped Derm 21:452–453, 2004 Clear cell sarcoma Ped Derm 23:53–55, 2006 Clear cell syringofibroadenoma of Mascaro – subungual papule BJD 144:625–627, 2001 Collagenoma; acquired collagenoma - personal observation

Acral Papules and Nodules; Knuckle Papules; Papules, Digital Comedo nevus of the palm (porokeratotic eccrine duct and hair follicle nevus) BJD 101:717–722, 1979 Congenital self-healing reticulohistiocytosis Cutaneous epithelioid sarcoma-like hemangioendothelioma – papules of toes AD 149:459–465, 2013 Dermatofibroma - digital papule; papule of foot

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Fibroma of the tendon sheath JAAD 11:625–628, 1984 Fibro-osseous pseudotumor of the digit – hyperkeratotic brown papule of the toe tip AD 147:975–980, 2011; Cancer 58:2103–2109, 1986 Fibrous hamartoma of infancy – congenital plantar nodule Ped Derm 21:506–507, 2004

Dermatofibrosarcoma protuberans – of the sole Dermatology 192:280–282, 1996

Fibrous histiocytoma JAAD 50:134–136, 2004

Digital fibrous tumor of childhood – toe nodule AD 131:1195–1198, 1995

Fibrosarcoma - congenital fibrosarcoma Ped Derm 23:330–334, 2006; JAAD 50:S23–25, 2004; Ped Derm 14:241–243, 1997

Digital myxoid cyst Derm Surg 27:591–593, 2001; JAAD 43:892, 2000

Fibrous dermatofibroma – periungual fibroma

Fibrous papule of the finger

Digital neurofibrosarcoma J Pediatr 51:566–70, 1957

Ganglion cyst of ankle (retinacular ganglion) JAAD 13:873–837, 1985; of finger Ped Derm 23:53–55, 2006

Dupuytren’s contracture (palmar fibromatosis) (fascial thickening) – starts as palmar nodule Clin in Dermatol 37:675–678, 2019;

Garlic clove tumor (fibroma) (acquired periungual fibrokeratoma) Rook p. 2846, 1998, Sixth Edition; AD 97:120–129, 1968

Am J Surg Pathol 1:255–270, 1977

Generalized eruptive histiocytoma

Eccrine angiokeratomatous hamartoma – red-violaceous keratotic nodule of lateral malleolus JAAD 55:S104–106, 2006

Giant cell tumor of the tendon sheath - single or multiple BJD 147:403–405, 2002; JAAD 43:892, 2000; nodules of the fingers J Dermatol 23:290–292, 1996; overlying dorsal digital interphalangeal crease J Hand Surg 5:39–50, 1980; subungual giant cell tumor of the tendon sheath Cutis 58:273–275, 1996 (nail dystrophy and swelling)

Eccrine angiomatous hamartoma - toes, fingers, palms and soles- skin-colored to blue Ped Derm 27:93–94, 2010; Cutis 71:449–455, 2003; JAAD 47:429–435, 2002; Ped Derm 13:139– 142, 1996; JAAD 37:523–549, 1997; Ped Derm 14:401–402, 1997; Ped Derm 18:117–119, 2001; Ped Derm 14:401–402, 1997; skin-colored nodule with blue papules JAAD 41:109–111, 1999; red plaque of palm Ped Derm 27:548–549, 2010 Primary eccrine porocarcinoma – acral red papules BJD 169:1059– 1061, 2013 Eccrine poroma – plantar red nodule AD 74:511–521, 1956; digital papule AD 74:511–512, 1956; palmar and plantar papules JAAD 55:S46–49, 2006; giant eccrine poroma Cutis 88:227–229, 2011; AMA Arch Derm 74:511–521, 1956 Eccrine spiradenoma – papule of proximal nail fold AD 140:1003– 1008, 2004 Eccrine syringofibroadenomatosis JAAD 39:356–358, 1998 Elastofibromas AAD 50:126–129, 2004; South Med J 77:1194– 1196, 1984; J Bone Joint Surg Br 69:468–469, 1987 Enchondroma Derm Surg 27:591–593, 2001; may be subungual Epidermal nevus - digital papule Epidermoid cyst - digital papule JAAD 43:892, 2000; palmar nodule subungual tumor Epithelioid sarcoma – red nodule of flexor finger or palm Cutis 95:83–86, 2015; JAAD 14:893–898, 1986; AD 121:389–393, 1985; Cancer 26:1029–1041, 1970; of sole Exostosis, subungual (variant of osteochondroma) Ped Derm 26:747–748,2009; JAAD 45:S200–201, 2001; Derm Surg 27:591– 593, 2001; Cutis 68:57–58, 2001; AD 128:847–852, 1992;JAAD 26:295–298, 1992; differentiate from carcinoma of the nailbed, Koenen’s tumor, pyogenic granuloma, verruca, glomus tumor, melanoma

Granular cell tumor (Abrikossoff tumor) - digital papule, paronychial nodule Cutis 35:355–356, 1985; Cutis 62:147–148, 1998; tip of great toe Ped Derm 24:235–237, 2007; red nodule of palm Ped Derm 27:656–657, 2010; plantar skin colored nodule Ped Derm 28:473–474, 2011 Infantile digital fibromatosis – skin-colored papule or nodule on dorsal or lateral aspect of digits at birth; multiple soft fibromas on dorsal digits AD 146:667–672, 2010; JAAD 60:535–537, 2009; Rare Tumors 47:146–147, 2009; Ped Derm 25:72–75, 2008; Ped Derm 24:280–284, 2007; Dermatol Surg 33:385–387, 2007; JAAD 49:974–975, 2003; AD 138:1245–1251, 2002; BJD 143:1107–1108, 2000; Ped Derm 8:137–139, 1991; J Cut Pathol 5:339–346, 1978; Arch Pathol 80:228–231, 1965; on lateral fifth finger AD 141:549– 550, 2005; solitary lesion of wrist Cancer 48:1807–1818, 1981; pink multilobulated nodule of toe Ped Dem 26:347–348, 2009; toe tip papule Ped Derm 33:453–454, 2016; giant tumor of 2nd toe Cutis 105:16, 20, 2020Infantile myofibromatosis - skin colored to pink, red, brown, multilobulated or purple-red multiple nodules or papules; multilobulated Ped Derm 27:29–33, 2010; JAAD 57:S30–32, 2007; Cutis 73:229–231, 2004; Cancer 7:953–978, 1954 Infundibular follicular cyst - digital papule Intraosseous epidermoid cysts JAAD 27:454–455, 1992 Juvenile aponeurotic fibroma (calcifying fibroma, juvenile palmoplantar fibromatosis) Ped Derm 24:280–284, 2007 Juvenile elastoma Juvenile digital fibromatosis (inclusion body fibromatosis) Kaposi’s sarcoma JAAD 59:179–206, 2008; digital papules JAAD 47:641–655, 2002; toes and feet BJD 162:854–859, 2010

Fibrolipomatous hamartoma – plantar nodule; heel nodule; annular hyperpigmented patch with cigarette paper wrinkling; resembles nevus lipomatosis superficialis and fibrous hamartoma of infancy Ped Derm 35:498–501, 2018; AD 148:1073–1078, 2012; subcutaneous of heels and hypothenar eminence of hand Ped Derm 36:728–729, 2019

Keloid

Superficial acral fibromyxoma – red keratotic toe nodule obliterating nail bed Cutis 97:260,281–282, 2016; Hum Pathol 32:704–714, 2016; Am J Surg Pathol 36:789–798, 2016

Leiomyosarcoma Ped Derm 14:241–243, 1997

Fibroma - digital papule or subungual fibroma Dermatol Clin 33:207–241, 2015; Derm Surg 27:591–593, 2001

Keratoacanthoma – backs of hands; digital papule AD 120:736–740, 1984; subungual AD 124:1074–1076, 1990; Cutis 46:26–28, 1990; of ankle Leiomyoma – of ankle Ped Derm 26:621–623, 2009 Leukemia cutis - digital papule; preleukemic state of monocytosis and neutropenia – perniotic lesions BJD 81:327–332, 1969; chronic myelomonocytic leukemia – chilblain-like lesions BJD 115:607–609, 1986; AD 121:1048–1052, 1985; chilblain-like leukemia cutis in

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

juvenile myelomonocytic leukemia Ped Derm 24:38–41, 2007; chronic myelomonocytic leukemia – chilblain-like lesions JAAD 50:S42–44, 2004; HTLV-1 leukemia/lymphoma - personal observation Lipoblastoma Ped Derm 23:514–515, 2006 Lipoma – periungual lipoma JAAD 51:S91–93, 2004; subungual lipoma BJD 149:418, 2003; adipose plantar nodules (congenital) BJD 142:1262–1264, 2000; palmar subcutaneous lipoma Cutis 40:29–32, 1987; multiple palmar lipomas BJD 159:757–758, 2008 Liposarcoma, myxoid variant JAAD 43:892, 2000 Low grade myxofibrosarcoma BJD 159:1315–1321, 2008 Lymphocytoma cutis

Multiple mucocutaneous neuromas (palisaded encapsulated and non-encapsulated neuromas) – lip, palmar, dorsal hand red papules AD 149:498–500, 2013 Myofibroma – skin-colored to hyperpigmented nodules of hand, mouth, genitals, shoulders JAAD 46:953–956, 2002; JAAD 46:477–490, 2002 Myopericytoma – periungual papules JAAD 54:1107–1108, 2006 Myxoid neurofibroma, periungual Cutis 69:54–56, 2002 Nerve sheath myxoma – most common on hands, fingers, knees AD 145:195–200, 2009 Neural fibrolipoma (neurolipomatosis, lipofibromatous hamartoma of nerves, macrodystrophia lipomatosa) AD 135:707–712, 1999; palmar nodule JAAD 53:528–529, 2005

Lymphoma, including cutaneous T-cell lymphoma (CTCL); CTCL -punctate red papules of soles AD 143:921–932, 2007; Woringer-Kolopp disease (pagetoid reticulosis) – red plaque of foot Cutis 99:311,354–355, 2017; acral plaques of hands Am J Dermatopathol 20:271–275, 1998; B-cell lymphoma overlying acrodermatitis chronica atrophicans associated with Borrelia burgdorferi infection JAAD 24:584–590, 1991; histiocytic lymphoma (true histiocytic lymphoma) JAAD 50:S9–10, 2004

Neurilemmoma - personal observation

Lymphomatoid papulosis Ped Derm 15:146–147, 1998; acral lymphomatoid papulosis JAAD 62:530–531, 2010; nodule of palmar surface of thumb in child BJD 171:138–146, 2014

Nevus sebaceus

Macroglobulinosis – Waldenstrom’s macroglobulinemia; ulcerated nodules and plaques with central necrosis; skin colored papules of dorsal hands with central crusts; peripheral neuropathy AD 146:165–169, 2010; bullous macroglobulinosis – bullae, scars, erosions, papules of dorsal hands JAAD 77:1145–1158, 2017 Malignant fibrous histiocytoma, myxoid variant – papule or nodule of ankle JAAD 48:S39–40, 2003; JAAD 43:892, 2000

Onycholemmal carcinoma – paronychia, crusted ulcer of nailfold, onycholysis JAAD 68:290–295, 2013

Neurofibroma - digital papule AD 124:1185–1186, 1988; of nail fold Neuroma, traumatic - digital papule; palisaded encapsulated neuroma AD 140:1003–1008, 2004; interdigital neuroma JAAD 38:815–819, 1998 Neurothekoma, subungual JAAD 52:159–162, 2005; red nodule of wrist Ped Derm 37:187–189, 2020 Nodular fibromatosis Nodular hidradenoma - personal observation

Onychomatricoma – red nodule of proximal nail bed AD 146:911– 916, 2010 Osteochondroma, subungual Ped Derm 24:584–585, 2007; Derm Surg 27:591–593, 2001

Malignant proliferating onycholemmal cyst J Cut Pathol 21:183, 1994

Osteoma cutis JAAD 39:527–544, 1998; JAAD 20:973–978, 1989

Melanocytic nevus

Perineurioma – soft tissue perineurioma; finger papule Cutis 75:233–237, 2005; subungual BJD 146:125–128, 2002

Melanoma Derm Surg 27:591–593, 2001; acral lentiginous melanoma BJD 155:561–569, 2006; amelanotic acral melanoma – red plaque of toe tip JAAD 69:700–707, 2013; subungual melanoma Melanoma of the soft parts (clear cell sarcoma) - foot, ankle, hand, wrist JAAD 38:815–819, 1998; plantar nodule Cutis 68:219–222, 2001; nodule of tendons of foot Cancer 65:367–374, 1990; subungual red papule AD 141:398–399, 2005 Merkel cell tumor Metastatic tumors – paronychial nodule of great toe – metastatic renal cell carcinoma AD 143:1067–1072, 2007; papule of distal paronychial fold – metastatic rectal carcinoma BJD 171:663–665, 2014; subungual keratotic papule – metastatic thyroid carcinoma NEJM 370:2131, 2014; plantar nodule of toe; pancreatic carcinoma AD 139:1497–1502, 2003; bronchogenic carcinoma - subungual papule Cutis 35:121–124, 1985; squamous cell carcinoma - palmar nodule; metastatic thyroid carcinoma - subungual crusted nodule of fifth finger NEJM 370:2131, 2014 Milia including multiple eruptive milia Mucinous carcinoma of skin JAAD 36:323–326, 1997 Multinucleate cell angiohistiocytoma - hands and wrists with grouped dome shaped 2–15 mm red to purple papules; women over 50 years old; thighs, knees, dorsal hands and fingers; red-brownviolaceous knuckle papules AD 147:975–980, 2011; New England Dermatological Society Conference, Sept 15, 2007; JAAD 38:143–175, 1998; AD 132:703–708, 1996; JAAD 30:417– 422, 1994; BJD 121:113–121, 1989; BJD 113:15, 1985

Osteosarcoma Derm Surg 27:591–593, 2001

Peripheral nerve sheath tumor Ped Derm 14:241–243, 1997 Pinkus tumors (fibroepithelioma of Pinkus) – variant of basal cell carcinoma; red papule of foot Am Fam Physician 77:1449–1450 Plantar fibromatosis (Ledderhose’s disease) – red plantar nodule; painful; may ulcerate Cutis 68:219–222, 2001; Curr Prob in Derm 8:137–188, 1996; skin colored plantar nodule AD 144:547–552, 2008; Postgrad Med J 79:158, 2003 Porokeratosis - punctate and palmoplantar porokeratosis Porokeratotic eccrine ostial and dermal duct nevus Ped Derm 23:465–466, 2006; J Cutan Pathol 15:393–395, 1988; BJD 101:717–722, 1979 Precalcaneal congenital fibrolipomatous hamartoma (bilateral pedal papules of the newborn) – plantar nodules over medial plantar heel AD 141:1161–1166, 2005; Ped Derm 22:355–356, 2005; Ped Derm 21:655–656, 2004; Med Cut Ibero Lat Am 18:9–12, 1990 Progressive nodular fibrosis of the skin - nodules on fingers JID 87:210–216, 1986 Pseudomyogenic hemangioendothelioma (epithelioid sarcoma-like hemangioendothelioma) – multifocal acral papules and nodules JAMA Derm 149:459–465, 2013 Reactive fibrous papule of the fingers (giant-cell fibroma) – fingers and palms Dermatologica 143:368–375, 1971 Rhabdomyosarcoma Curr Prob Derm 14:41–70, 2002; Ped Derm 14:241–243, 1997 Schwannoma Ped Derm 23:53–55, 2006

Acral Papules and Nodules; Knuckle Papules; Papules, Digital

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Sclerosing perineuroma – palmar nodule, digital nodule Ped Derm 21:606–607, 2004; BJD 146:129–133, 2002; tender pink papule of dorsal finger AD 147:975–980, 2011

PRIMARY CUTANEOUS DISEASE

Seborrheic keratosis and stucco keratosis – especially around ankles and dorsal aspects of fee AD 105:859–861, 1972

Acral psoriasiform hemispherical papulosis Dermatology 189:159– 161, 1994

Sinus histiocytosis with massive lymphadenopathy (RosaiDorfman disease) - granuloma annulare-like lesion JAAD 37:643–646, 1997

Acrokeratoelastoidosis of Costa J Cut Pathol 25:580–582, 1998; J Cutan Pathol 17:358–370, 1990; Dermatologica 171:8–11, 1985; AD 82:362–366, 1960;

Spindle cell hemangioendothelioma – multiple subcutaneous nodules; palmar giant cobblestoning; hypertrophy of hand Cutis 79:125–128, 2007

Acrokeratosis verruciformis of Hopf Ped Derm 27:93–94, 2010; AD 141:515–520, 2005;

Spiradenocarcinoma – nodule of hand Cutis 69:455–458, 2002; J Surg Oncol 43:131–133, 1990 Spitz nevus Squamous cell carcinoma; Derm Surg 27:591–593, 2001; subungual squamous cell carcinoma JAAD 11:291–298, 1984; periungual Cutis 78:173–174, 2006

Acanthosis nigricans

AD 130:508–512, 1994; Ann DV 115:1229–1232, 1988; Dermatol Zeitschr 60:227–250, 1931 Acute parapsoriasis (pityriasis lichenoides et varioliformis acuta) (Mucha-Habermann disease) – rare lesions of palms and soles AD 123:1335–1339, 1987; AD 118:478, 1982 Circumscribed acral hypokeratosis – pink atrophic patch of medial hand AD 145:195–200, 2009

Storiform collagenoma (sclerotic fibroma) Cutis 64:203–204, 1999

Congenital hypertrophy of the lateral nail folds of the hallux

Superficial acral fibromyxoma – fingers, toes, palms and soles BJD 159:1315–1321, 2008; nodule in paronychial fold AD 145:479–484, 2009

Ped Derm 5:243–245, 1989

Synovial sarcoma Ped Derm 23:53–55, 2006

Dermatitis herpetiformis-like spongiotic dermatitis - personal observation

Syringomas AD 140:1161–1166, 2004; Cutis 59:213–216, 1997; AD 113:1435–1436, 1977; with calcinosis cutis resembling milia JAAD 23:372–375, 1990 Syringomatous carcinoma – multilobulated digital nodule BJD 144:438–439, 2001

Darier’s disease - acrally distributed JAAD 30:860–862, 1994; hemorrhagic acral Darier’s disease Hautarzt 51:857–861, 2000

Digital papular calcific elastosis J Cutan Pathol 17:358–370, 1990 Distal subungual corn – tender acral pigmented keratotic subungual papule BJD 171:69–72, 2014 Ectopic plantar nail BJD 149:1071–1074, 2003

Trigger finger

Eosinophilic pustular folliculitis

Vascular and myxoid fibromas of the fingers – multiple warty lesions of palms and fingers JAAD 2:425–431, 1980

Epidermolysis bullosa – dystrophic

Verrucous acanthoma - digital papule Verrucous carcinoma – epithelioma cuniculatum of sole; of feet and legs JAAD 56:S2–32, 2007 Waldenstrom’s macroglobulinemia with cutaneous granulomas; IgM storage papules - red papules of lower legs AD 145:77–82, 2009

Epidermolysis bullosa simplex with mottled pigmentation of neck, upper trunk, arms and leg with or without keratoderma (punctate palmoplantar keratoses); cutaneous atrophy, nail dystrophy; wart-like hyperkeratotic papules of axillae, wrists, dorsae of hands, palms and soles; P25L mutation of keratin 5 JAAD 52:172–173, 2005; BJD 150:609–611, 2004; Clin Genet 15:228–238, 1979; dominant dystrophic

Xanthomatized giant cell tumor of the tendon sheath – yellow nodule of fingertip AD 145:931–936, 2009

Epidermolysis bullosa - ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013

PARANEOPLASTIC DISORDERS

Epidermolytic hyperkeratosis

Neutrophilic panniculitis of myelodysplasia – red nodules of legs and soles; MYSM1 deficiency; short stature Ped Derm 36:258–259, 2019

Erythema elevatum diutinum - knuckle pads (juxta-articular nodules), papules BJD 164:675–677, 2011; JAAD 49:764–767, 2003; Cutis 67:381–384, 2001; Ped Derm 15:411–412, 1998; violaceous plaques over lower legs BJD 159:733–735, 2008; including EED associated with HIV disease - digital papule; of feet cobblestoned multilobular nodules of foot in HIV disease AD 144:933–938, 2008; red-brown plaques of fingers and knees JAAD 65:469–471, 2011; papules of proximal nail fold

Paraneoplastic granuloma annulare – annular papules of sole JAAD 79:913–920, 2018

Filiform hyperkeratosis of the palms (multiple minute digitate hyperkeratosis) AD 142:235–240, 2006

Erythema elevatum diutinum – associated with hairy cell leukemia, chronic lymphocytic leukemia Necrobiotic xanthogranuloma with paraproteinemia AD 133:97–102, 1997

Flegel’s disease (hyperkeratosis lenticularis perstans)

PHOTODERMATITIS Actinic granuloma Degenerative collagenous plaques of the hands Dermatologica 107:164–168, 1953; BJD 106:337–344, 1982 Digital papular calcific elastosis AD 137:379–381, 2001 Polymorphic light eruption

Focal acral hyperkeratosis – papules of knuckles and along Wallace’s lines AD 142:235–240, 2006; Ped Derm 21:128–130, 2004; AD 132:1365–1370, 1996; Dermatology 188:28–31, 1994; BJD 109:97–103, 1983 Granuloma annulare - of dorsal fingers and palms AD 142:49–54, 2006; JAAD 3:217–230, 1980; subcutaneous granuloma annulare mimicking knuckle pads; painful acral granuloma annulare – red nodules of palms AD 142:49–54, 2006; red papules of palms

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

mimicking erythema multiforme J Drugs in Dermatol 12:694–697, 2013

Pityriasis rubra pilaris

Greither’s palmoplantar keratoderma (transgradiens et progradiens palmoplantar keratoderma) Cutis 65:141–145, 2000

Psoriasis

Infantile acropustulosis – acral papules and pustules JAAD 65:763–767, 2011; AD 115:831–833, 1979; AD 115:834–836, 1979 Keratoelastoidosis marginalis of the hands – hyperkeratotic papules of hands in elderly Dermatologica 131:169–175, 1954 Keratosis lichenoides chronica – vesicular and papular lesions of palms and soles BJD 144:422–424, 2001; JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; AD 131:609–614, 1995; AD 105:739–743, 1972 Knuckle pads (heloderma) – familial, autosomal dominant; idiopathic (fibromatosis), keratotic knuckle pads unassociated with palmoplantar keratoderma Caputo, 2000, p.47; Rook p.1555–1556, 1998, Sixth Edition; AD 129:1043–1048, 1993; trauma-induced, associated with Dupuytren’s contracture, Ledderhose’s disease, Peyronie’s disease, Bart-­Pumphrey syndrome – mixed sensorineural and conductive deafness, leukonychia, and knuckle pads; autosomal dominant Ped Derm 17:450–452, 2000; Cutis 57:241–242, 1996; associated with palmoplantar keratoderma, acrokeratoelastoidosis of Costa, keratoderma hereditaria mutilans, pseudoxanthoma elasticum; secondary knuckle pads due to chewing, bulimia; occupational – plumbers, carpet layers, mechanics, tailors, textile workers, plasterers, live chicken hangers; sports – football, surfers, boxers AD 143:1458–1460, 2007 Lenticular acral keratosis in washerwomen Int J Dermatol 37:532– 537, 1998 Lichen nitidus - digital papule, knuckle pads AD 134:1302–1303, 1998 Lichen planus follicularis tumidus – brown-violaceous acral plaques, cysts, milia, comedonal openings Clin Exp Dermatol 45:638–641, 2020 Lichen planus photo-induced lichen planus - personal observation Lichen simplex chronicus - knuckle pads

Progressive symmetric erythrokeratoderma - personal observation Reactive perforating collagenosis of childhood - digital papule

PSYCHOCUTANEOUS DISEASES Bulimia nervosa - Russell’s sign (crusted knuckle nodules) Clin Orthop 343:107–109, 1997; JAAD 12:725–726, 1985; perniosis Clin Sci 61:559–567, 1981; pseudo knuckle pads (calluses on 2nd 5th MCP joints) Psychol Med 9;429–48, 1979

SYNDROMES Acral pseudolymphomatous angiokeratoma in children (APACHE) unilateral multiple persistent vascular papules on hands and feet (cutaneous pseudolymphoma) JAAD 48:S15–17, 2003; BJD 145:512–514, 2001; JAAD 38:143–175, 1998; BJD 124:387–388, 1991; red papules JAAD S209–211, 2001; acral pseudolymphomatous angiokeratoma Am J Dermatopathol 16:130–133, 1994 Adams-Oliver syndrome – autosomal dominant; terminal transverse limb anomalies, aplasia cutis congenita, cutis marmorata telangiectatica congenita, severe growth retardation, aplasia cutis congenita of knee, short palpebral fissures, dilated scalp veins, simple pinnae, skin tags on toes, hemangioma, undescended testes, supernumerary nipples, hypoplastic optic nerve, congenital heart defects Ped Derm 24:651–653, 2007 Bart-Pumphrey syndrome - knuckle pads, leukonychia, deafness, and palmoplantar hyperkeratosis Congenital hemidysplasia, ichthyosiform erythroderma, and limb defects (CHILD syndrome) – hyperkeratotic papules of ears, dorsal foot Ped Derm 30:250–252, 2013; fingertip nodules (verruciform xanthomas) JAAD 50:S31–33, 2004; verruciform xanthoma – giant red plaque of lateral foot in CHILD syndrome Ped Derm 27:551– 553, 2010

Lichen sclerosus et atrophicus – wrists, palms, soles AD 115:884, 1979

Cowden’s syndrome - acrokeratosis verruciformis-like lesions AD 142:625–632, 2006; AD 106:682–690, 1972; Ann Int Med 48:136– 142, 1963; translucent papules on palms and soles JAAD 11:1127– 1141, 1984; AD 114:743–746, 1978

Migratory angioedema - plantar nodule Ped Derm 15:97–102, 1998

Dermo-chondro-corneal dystrophy

Mosaic acral keratosis Clin Exp Dermatol 15:361–362, 1990

Digitocutaneous dysplasia – X-linked dominant; digital fibromas, atrophic plaques with appearance of hyperpigmentation, metacarpal and metatarsal disorganization with resultant brachydactyly and clinodactyly, dysmorphic features including frontal bossing, broad nasal root, telecanthus and epicanthal folds, ptosis of the eyelids, conical teeth, dental fissures, hypodontia, accessory gingival frenula, enamel hypoplasia JAAD 56:S6–9, 2007

Lichen striatus - personal observation

Necrolytic acral erythema – serpiginous, verrucous plaques of dorsal aspects of hands, legs; associated with hepatitis C infection JAAD 50:S121–124, 2004 Onychoheterotopia – mimics polydactyly; nail tissue growing outside of classic nail unit; congenital or familial; seen in Pierre-Robin syndrome and abnormal long arm chromosome 6 JAAD 64:161– 166, 2011 Pachydermodactyly – bilateral asymptomatic swelling of soft tissues surrounding the PIP joints of second and fourth fingers; benign fibromatosis of fingers of young men; thought to be trauma-related AD 144:1651–1656, 2008; Clin Rheumatol 26:962–964, 2007; Clin Exp Dermatol 28:674–675,2003; Ann DV 125:247–250, 1998; BJD 133:433–437, 1995; AD 111:524, 1975; Bull Soc Fr Dermatol Syphiligr 80:455–458, 1973

Ehlers-Danlos syndrome (molluscum pseudotumor) - knuckle pads Ellis van Creveld syndrome – polydactyly JAAD 46:161–183, 2002; Ped Derm 18:68–70, 2001 Epidermodysplasia verruciformis J Cut Med Surg 8:357–360, 2004; J Eur Acad Derm Venereol 17:382–386, 2003; Curr Top Microbiol Immunol 186:157–175, 1994

Palmoplantar keratoderma, epidermolytic (Vorner’s) - papules on knuckles BJD 125:496, 1991; Collie-Davies palmoplantar keratoderma - personal observation

Familial chilblain lupus erythematosus – acral cyanotic papules; paronychia, acral erythema, acral papules, necrotic ulcers, facial ulcers, mutilation of fingers, ear lesions; mutation of exonuclease III domain of 3’ repair exonuclease 1 (TREX1) JAMA Derm 151:426– 431, 2015; BJD 166:212–214, 2012

Pityriasis lichenoides chronica (guttate parapsoriasis) JAAD 55:557–572, 2006Pityriasis rosea - personal observation

Familial multiple acral mucinous fibrokeratomas - verrucous papules of the fingers JAAD 38:999–1001, 1998

Acral Papules and Nodules; Knuckle Papules; Papules, Digital Familial histiocytic dermatoarthritis - knuckle pads Farber’s disease (disseminated lipogranulomatosis) – red papules and nodules of joints and tendons of hands and feet; deforming arthritis; papules, plaques, and nodules of ears, back of scalp and trunk Am J Dis Child 84:449–500, 1952 Fibroblastic rheumatism – symmetrical polyarthritis, nodules over joints and on dorsal hands, palms, elbows, knees, ears, neck, Raynaud’s phenomenon, sclerodactyly; joint contractures, thick palmar fascia; scalp nodules, red tender swelling of toe tips, periarticular nodule; skin lesions resolve spontaneously Cutis 100:354, 356–357, 2017; JAAD 66:959–965, 2012; AD 139:657– 662, 2003; Ped Derm 19:532–535, 2002; AD 139:657–662, 2003; AD 131:710–712, 1995; Clin Exp Dermatol 19:268–270, 1994; AD 131:710–712, 1995; Clin Exp Dermatol 19:268–270, 1994; JAAD 14:1086–1088, 1986; Rev Rheum Ed Fr 47:345–351, 1980; periungual papules Ped Derm 19:532–535, 2002

Ledderhose’s nodules (plantar fibromatosis) JAAD 41:106–108, 1999; Dupuytren’s contracture (palmar fibromatosis) and/or Peyronie’s disease - knuckle pads Lipoid proteinosis – acral papules on fingers; mutation in extracellular matrix protein-1 (ECM1) AD 147:857–862, 2011; BJD 151:413– 423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002; digital papule AD 132:1239–1244, 1996; Virchows Arch (Pathol Anat) 273:285–319, 1929 Lipomatosis of the hands - Madelung-Launois-Bensalide syndrome Maffucci’s syndrome (enchondromatosis) – enchondromas and multiple venous malformations; spindle cell hemangioendothelioma; oral and intra-abdominal venous and lymphatic anomalies; short stature, shortened long bones with pathologic fractures; enchondromas undergo sarcomatous change in 30–40%; breast, ovarian, pancreatic, parathyroid, pituitary tumors Ped Derm 25:205–209, 2008; JAAD 56:541–564, 2007;

Francois syndrome (dermochondrocorneal dystrophy) - knuckle pads; nodules on hands, nose, and ears Ann DV 104:475–478, 1977; AD 124:424–428, 1988

Cutis 79:115–117, 2007; Cutis 69:21–22, 2002; J Laryngol Otol 115:845–847, 2001; Ped Derm 17:270–276, 2000; Ped Derm 12:55–58, 1995;

Goltz’s syndrome (focal dermal hypoplasia) – papillomas of toes and lips AD 145:218–219, 2009; syndactyly, hypoplasia or aplasia of digits, clawhand or foot (gampsodactyly), polydactyly, oligodactyly, asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberry-like papillomas of lips, perineum, acrally, at perineum, buccal mucosa; linear alopecia, xerosis; scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones AD 143:109–114, 2007; Cutis 53:309–312, 1994; J Dermatol 21:122–124, 1994; JAAD 25:879–881, 1991; AD 86:708–717, 1962

Mal de Meleda - knuckle pads Ped Derm 14:186–191, 1997

Hereditary acrokeratotic poikiloderma of Weary – vesiculopustules of hands and feet at age 1–3 months which resolve; widespread atopic dermatitis-like dermatitis; diffuse poikiloderma with striate and reticulate atrophy; keratotic papules of hands and feet, elbows and knees; autosomal dominant AD 103:409–422, 1971 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) Am J Med 82:989–997, 1987 Hereditary papulotranslucent acrokeratoderma AD 108:108–110, 1973 Hereditary progressive mucinous histiocytosis – autosomal dominant; skin-colored or red-brown papules; nose, hands, forearms, thighs JAAD 35:298–303, 1996; AD 130:1300–1304, 1994 Hidrotic ectodermal dysplasia (Clouston’s syndrome) – syringofibroadenomas – flat-topped coalescing papules (acral) JAAD 40:259–262, 1999 Hunter’s syndrome - MPS II - knuckle pads Ped Derm 12:370–372, 1995 Incontinentia pigmenti – painful subungual keratotic tumor of IP JAAD 52:727–729, 2005; JAAD 50:S45–52, 2004; JAAD 47:169– 187, 2002; J Hand Surg 18B:667–669, 1993; AD 124:29–30, 1988; JAAD 13:913–918, 1985; AD 94:632–635, 1966 Infantile systemic hyalinosis - knuckle pads Ped Derm 11:52–60, 1994

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MEN2A – multiple sclerotic fibromas presenting as elongated papules of trunk and heel nodules AMA Derm 153:1298–1301, 2017 Multicentric reticulohistiocytosis – digital papule; multiple papules on proximal nail folds (periungual papules) (“coral beads”) knuckle pads; lateral finger papules, yellow papules and plaques AD 148:228–232, 2012; Cutis 85:153–155, 2010; BJD 161:470–472, 2009; AD 144:1383–1388, 2008; AD 144:1360–1366, 2008; AD 144:105–110, 2008; JAAD 58:541–543, 2008; JAAD 56:302–316, 2007; JAAD 53:1075–1079, 2005; AD 140:919–921, 2004; JAAD 49:1125–1127, 2003; JAAD 25:948–951, 1991; AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; Clin Exp Dermatol 5:267–279, 1980; AD 97:543–547, 1968 Multiple exostoses syndrome JAAD 25:333–335, 1991 Multiple symmetric lipomatosis of the soles JAAD 26:860–862, 1992; of the hands Clin Exp Dermatol 14:58–59, 1989 Nager acrofacial dysostosis - personal observation Neurofibromatosis type 1 - digital papule, knuckle pads Neutrophilic dermatosis (pustular vasculitis) of the dorsal hands – variant of Sweet’s syndrome – acral papules AD 138:361–365, 2002 Nevoid basal cell carcinoma syndrome – acral popular basal cell carcinomas in children BJD 171:1227–1229, 2014 Novel fibrosing disorder – subcutaneous fibrotic nodules, progressive distal joint contractures, marfanoid stature, forehead nodules, skin tightening (sclerodermoid changes), palmoplantar nodules, nodules of elbows and knees, linear arrays of nodules later in course; differentiate from Marfan’s syndrome, congenital contractural arachnodactyly, Winchester syndrome, multicentric osteolysis nodulosis and arthropathy (MONA) syndrome BJD 163:1102–1115, 2010

Juvenile hyaline fibromatosis – pearly white papules of face and neck; larger papules and nodules around nose, behind ears, on fingertips, knuckle pads; multiple subcutaneous nodules of scalp, trunk, and hands, feet, and extremities, papillomatous perianal papules; joint contractures, skeletal lesions, gingival hyperplasia, stunted growth ; mutation of capillary morphogenesis protein 2 gene BJD 157:1037–1039, 2007; AD 121:1062–1063, 1985; AD 107:574–579, 1973

Ollier syndrome – multiple enchondromas

Kindler’s syndrome - acral keratoses

Palmar fibromatosis

Olmsted syndrome – plantar squamous cell carcinoma BJD 145:685–686, 2001 Pachydermodactyly – benign fibromatosis of fingers of young men; knobby knuckles Ped Derm 24:280–284, 2007; AD 129:247–248, 1993; JAAD 27:303–305, 1992; AD 111:524, 1975 Pachyonychia congenita - papules on the fingers

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Patau’s syndrome (trisomy 13) – polydactyly, simian crease of hand, loose skin of posterior neck, parieto-occipital scalp defects, abnormal helices, low set ears, hyperconvex narrow nails Ped Derm 22:270–275, 2005 Proteus syndrome – cerebriform connective tissue nevus JAAD 78:725–732, 2018; Ped Derm 5:14–21, 1988 Pseudohypoparathyroidism and pseudopseudohypoparathyroidism – osteoma cutis; nodule of heel or toe; short 5th digit, short stature; GNAS mutation Ped Derm 36:365–367, 2019 PTEN hamartoma-tumor syndrome – neuromas; corneal nerve hypertrophy AD 142:625–632, 2006 Reflex sympathetic dystrophy with chilblain-like lesions - digital papule - personal observation Reactive arthritis – keratoderma blenorrhagicum Semin Arthritis Rheum 3:253–286, 1974 Relapsing eosinophilic perimyositis – fever, fatigue, and episodic muscle swelling; erythema over swollen muscles; red palmar papules BJD 133:109–114, 1995 Relapsing polychondritis - personal observation Reticular erythematous mucinosis syndrome (REM syndrome)

ground water consumption; especially in Bangladesh and West Bengal, India; also in India, Argentina, China, Chile, Thailand, and Mexico SkinMed 11:211–216, 2013 Mercury poisoning – skin colored to slightly red papules or papulovesicles of palms or soles JAAD 49:1109–1111, 2003

TRAUMA Athletes’ nodules – skin colored nodules of ankle and dorsal foot AD 145:1325–1330, 2009 Callosities - occupational (carpenters, live chicken hangers, frictional) Contact Derm 17:13–16, 1987 Chilblains (perniosis) – tender, pruritic red or purple digital papules Mayo Clin Proc 89:207–215, 2014; BJD 163:645–646, 2010; Cutis 84:15,27–29, 2009; JAAD 47:S263–265, 2002; JAAD 45:924–929, 2001; plantar nodule Ped Derm 15:97–102, 1998; toe tips JAMA Derm 150:329–330, 2014 Clavus Delayed pressure urticaria – nodules of soles JAAD 29:954–958, 1993

Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – papules, annular targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAAD 21:374–377, 1989

Dermatophagia ("wolf-biter") Cutis 59:19–20, 1997

Schopf-Schulz-Passarge syndrome(congenital ectodermal dysplasia) – acral papules of syringocystadenoma papilliferum and syringofibroadenoma; reticulated palmoplantar keratoderma, hypodontia, hypotrichosis, nail dystrophy, multiple eyelid apocrine hidrocystomas, no dermatoglyphics of fingertips; mutation in WNT10A JAAD 65:1066–169, 2011

Frictional lichenoid dermatitis

Scleroatrophic syndrome of Huriez - palmar nodule, scleroatrophy of the hands BJD 137:114–118, 1997

Painful piezogenic pedal papules (fat herniation) JAAD 55:290–301, 2006

Stiff skin syndrome - knuckle pads Ped Derm 3:48–53, 1985

Plantar trauma - plantar nodule Ped Derm 15:97–102, 1998

Sweet’s syndrome JAAD 40:838–841, 1999; drug-induced Sweet’s syndrome – red plaques, nasal ulcers, perianal ulcers - celecoxib, G-CSF, all-trans retinoic acid JAAD 45:300–302, 2001; subcutaneous Sweet’s syndrome – nodules of hands and feet; mimicking panniculitis Ped Derm 36:723–724, 2019

Skier’s thumb Acta Orthop Belg 65:440–446, 1999; Sports Med 19:73–79, 1995

Terminal osseous dysplasia and pigmentary defects – X-linked dominant; digital fibromas, punched out pigmentary anomalies of face and scalp, eye anomalies (colobomas, hypertelorism) Ped Derm 24:280–284, 2007; Am J Med Genet 94:102–112, 2000

Writer’s callus - digital papule

Trichorhinophalangeal dysplasia syndrome (Laugier-Gideon syndrome) Ped Derm 13:212–218, 1996 Tuberous sclerosis – periungual angiofibromas (Koenen’s tumors) JAAD 64:442–444, 2011; JAAD 63:244–251, 2010; NEJM 359:1381, 2008; JAAD 18:369–372, 1988; digital papules J Clin Neurol 7:221–224, 1992 WHIM syndrome – warts, hypoglobulinemia, infections, myelokathexis; mutation in CXCR4 AD 146:931–932, 2010

Ectopic nail – post-traumatic JAAD 50:323–324, 2004; acquired post-traumatic ectopic nail (onychoheterotopia) SKINmed 12:306– 307, 2014 Garrod’s pads - violinist’s knuckles - thickened skin over the interphalangeal joints from intense flexion of the tendons of the fingers Hypertrophic scar – plantar giant nodule BJD 145:1005–1007, 2001

Surfer’s nodules of foot Traumatic neuroma due to treatment of supernumerary digit Ped Derm 20:108–112, 2003

VASCULAR Acquired digital arteriovenous malformation – periungual vascular papule JAAD 56:S122–124, 2007 Acral pseudolymphomatous angiokeratoma of children (APACHE) unilateral multiple persistent vascular papules on hands and feet; may have keratotic surface or collar JAAD 38:143–175, 1998; BJD 124:387–388, 1991; AD 126:1524–1525, 1990; BJD 119 (Suppl):135, 1988

Winchester’s syndrome AD 111:230–236, 1975

Acroangiodermatitis of Mali - pseudo-Kaposi’s sarcoma (BluefarbStewart syndrome); chronic venous insufficiency, arteriovenous malformations, paralysis – tops of first and second toes Acta DV (Stockh) 75:475–478, 1995; Int J Dermatol 33:179–183, 1994

Xeroderma pigmentosum

Angiofibroma - digital papule

WILD syndrome – warts, immune deficiency, lymphedema, anogenital dysplasia AD 146:1196–1197, 2010

TOXINS Arsenical keratoses – palms and soles; resemble corns; fingers, backs of hands JID 4:365–383, 1941; squamous cell carcinoma of palm; arsenical keratosis; arsenic toxicity due to contaminated

Angiokeratoma circumscriptum – foot; angiokeratoma of Mibelli – autosomal dominant; acral dark red papules of dorsal fingers and toes of young women with recurrent chilblains and acrocyanosis JAAD 45:764–766, 2001; AD 106:726–728, 1972; AD 95:166–175, 1967; eruptive unilateral angiokeratomas AD 144:1663–1664, 2008

Acrochordons (Skin Tags) Angiokeratomas – plantar; of nail fold; acral angiokeratomas of Mibelli in Turner’s syndrome – blue-black keratotic vascular papules Ped Derm 27:662–664, 2010 Angiolymphoid hyperplasia with eosinophilia Cutis 58:345–348, 1996 Arteriovenous aneurysms

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Vasculitis - plantar nodule JAAD 47:S263–265, 2002; Ped Derm 15:97–102, 1998 Venous aneurysm – painful blue nodule of hand AD 140:1393– 1398, 2004 Venous lake Verrucous hemangioma JAAD 42:516–518, 2000

Arteriovenous malformation, digital – red papule, subungual blue papule BJD 147:1007–1011, 2002; BJD 136:472–473, 1997 Blue rubber bleb nevus syndrome – blue palmar and plantar nodules; nail fold lesions

ACROCHORDONS (SKIN TAGS)

Cholesterol emboli AD 122:1194–1198, 1986

Acrochordon (skin tag); normal finding Dermatologica 174:180–183, 1987; giant lumbar polypoid tumor with bullae Acta DV Croat 27:127–128, 2019

Chylous lymphedema – xanthomas of toes and feet BJD 146:134– 137, 2002 Cutaneous keratotic hemangioma AD 132:705, 1996 Digital verrucous fibroangioma Acta DV 72:303–304, 1992 Disseminated congenital hemangiomatosis - personal observation Emboli - plantar nodule Ped Derm 15:97–102, 1998; atrial myxoma – acral papule; painful pink or purpuric papules as a manifestation of Carney complex JAAD 55:551–553, 2006; BJD 147:379–382, 2002 Epithelioid hemangioendothelioma JAAD 36:1026–1028, 1997 Epithelioid hemangioma JAAD 35:851–853, 1996 Glomus tumors - digital papule, subungual Derm Surg 27:591–593, 2001 Granulomatosis with polyangiitis – acral plaque JAAD 82:799– 816, 2020Hemangioma – of foot or toes subungual Histiocytoid hemangioma JAAD 21:404–409, 1989 Infantile hemangiopericytoma Ped Derm 14:241–243, 1997 Intravascular papillary endothelial hyperplasia - vascular nodule of palmar third finger BJD 166:1147–1149, 2012 Lymphangioma circumscriptum Masson’s intravascular papillary endothelial hyperplasia (pseudoangiosarcoma) Cutis 59:148–150, 1997 Neonatal hemangiomatosis - digital papule Palmar varices – of palmar creases of elderly BJD 91:305–314, 1974 Polyarteritis nodosa - palmar and plantar nodules AD 130:884–889, 1994; Ped Derm 15:103–107, 1998; nodules along the course of superficial arteries around knee, anterior lower leg and dorsum of foot Ann Int Med 89:666–676, 1978; cutaneous infarcts presenting as tender nodules Pseudopyogenic granuloma Ann DV 110:251–257, 1983 Pyogenic granuloma - digital papule Dermatol Surg 27:591–593, 2001; of nail bed BJD 163:941–953, 2010 Retiform hemangioendothelioma JAAD 38:143–175, 1998; macrodactyly with swelling of distal finger JAAD 65:233–235, 2011 Spindle cell hemangioendothelioma (hemangioma) – red-blue or hyperkeratotic nodules of soles AD 142:641–646, 2006; BJD 142:1238–1239, 2000 Spindle cell vascular anomaly - personal observation Takayasu’s arteritis - red or flesh colored nodule AD 123:796–800, 1987, AD 122:201–204, 1986 Thrombosis of deep palmar vein JAMA 111:2007–2008, 1938; plantar nodule Ped Derm 15:97–102, 1998; thrombosed vein – plantar surface Clin Podiatr Med Surg 13:85–89, 1996 Tufted angioma of the palm Ped Derm 18:456–457, 2001

Associations with multiple acrochordons:  Acanthosis nigricans with insulin resistance Indian J Dermatol 65:112–117, 2020   Acromegaly Clin Dermatol 24:256–259, 2006  Aicardi-Goutieres syndrome – infantile spasms, agenesis of corpus callosum, chorioretinal lacunae; multiple nevi, skin tags, hemangiomas, angiosarcoma Am J Med Genet A 138:254–258, 2005   Bannayan-Riley-Ruvalcaba syndrome JAAD 53:639–643, 2005  Beare-Stevenson cutis gyrate syndrome – corrugated skin furrows, acanthosis nigricans, craniofacial anomalies, skin tags, prominent umbilical stump Am J Med Genet 44:82–89, 1992   Birt-Hogg-Dube syndrome Am J Clin Dermatol 19:87–101, 2018   Cowden’s syndrome – personal observation   Crohn’s disease – perianal skin tags Br J Surg 91:801–814, 2004  Duane anomaly, familial and urogenital abnormalities with bisatellited marker derived from chromosome 22 – Duane retraction syndrome – congenital cranial dysinnervation disorder with paradoxical lateral rectus muscle innervation of the affected eye by aons meant to innervate the ipsilateral medial rectus muscle (resultant varying degrees of cocontraction); sensorineural deafness and preauricular skin tags Am J Med Genet 47:925–930, 1993   Familial idiopathic fibroepithelial skin tags  Multiple basaloid follicular hamartoma syndrome – chondrosarcoma, acrochordons, and seborrheic keratosis BJD 146:1068– 1070, 2002   Nevoid basal cell carcinoma syndrome JAAD 44:789–794, 2001  Obesity – metabolic syndrome JAAD 81:1037–1057, 2019; JAAD 56:901–916, 2007  Oculocerebrocutaneous syndrome – orbital cyst, cerebral malformations, skin tags, focal hypoplasia skin lesions Am J Ophthalmol 99:142–148, 1985   Sign of Leser-Trelat NEJM 317:1582–1587, 1987  Tuberous sclerosis – pancreatic islet-cell tumors and acrochordons; TSC2 mutations J Eur Acad DV 31:e507–508, 2017; Am J Med Genet A 140:1669–1672, 2006

ACROMEGALIC FEATURES Acquired generalized lipodystrophy – acromegalic features Acromegaloid phenotype with cutis verticis gyrata of scalp and corneal leukoma (opaque cornea) (Rosenthal-­Kloepfer syndrome) – autosomal dominant; hyperplasia and folding of facial skin Arch Ophthalmol 68:722–726, 1962 Acromegaly – prognathism, frontal bossing, widely spaced teeth, protruding thick lower lip, edematous thick eyelids, large triangular ears, large pores, oily hyperhidrotic skin, elongated blunt thickened fingers, large, furrowed tongue, hyperpigmentation mutation in GPR101 NEJM 371:2363–2374, 2014

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Beckwith-Wiedemann syndrome (IGF2) Bronchial carcinoid Neurosurg 50:1356–1359, 2002; Asian Cardiovasc Thorac Ann 10:273–274, 2002; insulin-like growth facor-1 Ann Thoracic Surg 88:1350–1352, 2009

ACRO-OSTEOLYSIS Clin Rheumatol 36:9–14, 2017; JAMA 255:2058, 1986; Am J Med 65:632, 1978

Cantu syndrome – congenital hypertrichosis, cardiomegaly, osteochondrodysplasia, coarse acromegalic facial features, deep plantar creases; mutation in ABCC9 Appl Clin Genet 17:15–21, 2018; Am J Med 92:191–194, 2000; Am J Med Genet 94:421–427, 2000; Am J Med Genet 69:138–151, 1997

Biliary cirrhosis with arthritis

Carney complex – acromegaly, facial lentigines, cutaneous myxoma, blue nevus of vulva; gain of function mutation of PRKACB (catalytic subunit alpha of cAMP-dependent protein kinase Ped Derm 36:160–162, 2019; NEJM 370:1065–1067, 2014

Epidermolysis bullosa

Congenital macrogingivae – profuse hypertrichosis of lower face, trunk, and extremities with acromegalic features Plast Reconstr Surg 27:608–612, 1962

Gaucher’s disease

Congenital total lipodystrophy (Berardinelli syndrome, Seip syndrome) – extreme muscularity and generalized loss of body fat from birth, acanthosis nigricans, acromegalic features, umbilical hernia, hyperinsulinemia (fasting and postprandial), early onset diabetes mellitus or glucose intolerance, hypertriglyceridemia/low HDL-C level, hirsutism, clitoromegaly J Clin Endocrinol Metab 85:1776–1782, 2000

Hajdu-Cheney syndrome

Hughes syndrome – acromegaloid features and thickened oral mucosa J Med Genet 22:119–125, 1985 Lichen myxedematosus Malan syndrome (NFIX) Minoxidil – pseudoacromegaly JAAD 48:962–965, 2003

Burns Diabetes mellitus Electrical injuries Ergot toxicity Frostbite Gout Granulomatosis with polyangiitis Hereditary sensory neuropathy Hyperparathyroidism Intestinal lymphangiectasia Juvenile rheumatoid arthritis Laminopathies Leprosy Lipodermatoarthritis Lipogranulomatosis, disseminated Lupus erythematosus, systemic

Multiple endocrine neoplasia syndrome

Mixed connective tissue disease

Pachydermoperiostosis primary (Touraine-Solente–Gole syndrome), secondary no macroglossia or prognathism; fingers clubbed

Mucopolysaccharidoses Neurogenic ulcerative acropathy

Phenytoin – fetal phenytoin syndrome; coarse facial features, enlarged lips and nose JAAD 18:721–741, 1988

Neuropathic arthritis

Pseudoacromegaly – autosomal recessive; skin ulcers, arthro-osteolysis, keratitis, oligodontia J Endocrine Soc1:1104–1109, 2017; Am J Med Genet 15:205–210, 1983; in Fabry’s disease Clin Exp Dermatol 38:137–139, 2013

Occlusive vascular disease

Pyoderma chronica glutealis complicated by acromegalic gigantism J Dermatol 25:242–245, 1998

Pachydermoperiostosis

Sanfilippo’s syndrome Short stature with pleonosteosis and periarticular fibrosis (Leri’s syndrome) – autosomal dominant; short stature and Mongoloid facies, thick palms and soles with accentuated creases, flexion contractures of digits, broad thumbs, genu recurvatum J Bone Joint Surg Am 41:397–408, 1959 Soto’s syndrome (cerebral gigantism) - acromegalic features, increased height and weight, large hands and feet, mental retardation; mutation in NSD1 gene Clin Chim Acta 470:31–35, 2017; Dev Med Child Neurol 11:796–797, 1969 Tatton-Brown-Rahman syndrome (DNMT3) Tumors – endometrial, pancreatic cell, small-cell lung cancer, adrenal adenomas, pheochromocytomas producing ectopic growth hormone releasing hormone Pituitary 9:221–229, 2006; Ann Oncol 12 Suppl 2: 589–594, 2001

Noggin mutations Osteoarthritis Osteomalacia Palmoplantar keratoderma, pes planus, onychogryphosis, periodontosis, arachnodactyly, and acroosteolysis BJD 115:243–248, 1986 Penttinen syndrome Polymyositis Porphyria cutanea tarda Progeria Psoriasis, pustular psoriasis, acrodermatitis continua of Hallopeau Pycnodysostosis Raynaud’s disease Reactive arthritis Rheumatoid arthritis Sarcoidosis Scleroderma Sezary syndrome

Weaver syndrome (E2H2))

Sjogren’s syndrome

X-linked acrogigantism NEJM 371:2363–2374, 2014

Syphilis

Adrenal Disease, Cutaneous Manifestations Trauma – repetitive trauma of digits/toes Vinyl chloride toxicity Werner’s syndrome

 DRENAL DISEASE, CUTANEOUS A MANIFESTATIONS Addison’s disease – diffuse hyperpigmentation, accentuated in flexures, palmar and plantar creases, nipples, genitalia, buccal mucosa, conjunctiva, vagina Cutis 76:97–99, 2005; universal melanosis; oral spots or patches JAAD 56:828–834, 2007; Cutis 76:97–99, 2005; Cutis 66:72–74, 2000; hyperpigmentation of vermilion border of lips, tongue, gingiva Ped Derm 25:215–218, 2008; tongue hyperpigmentation Cutis 76:97–99, 2005; vitiligo-like patches

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ronodular adrenal hyperplasia NEJM 369:2115–2125, 2013; NEJM 369:2105–2114, 2013 Multiple endocrine neoplasia syndrome (MEN I) – autosomal dominant; angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones; meningioma, ependymoma, prolactinoma, gastrinoma, bilateral adrenal hyperplasia AD 148:1317–1322, 2012; JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004; AD 133:853–857, 1997 Multiple endocrine neoplasia syndrome (MEN IIA) – cutaneous neuromas, itchy papules of scapulae and amyloid, medullary carcinoma of thyroid, pheochromocytoma, primary hyperparathyroidism; mutation in ret proto-oncogene BJD 164:245–256, 2011 Nelson’s syndrome – post-adrenalectomy diffuse hypermelanosis Ann Int Med 52:560–569, 1960

Adrenal disease – increased peripheral conversion of estrogen – breast hypertrophy Adrenal tumor with hemihypertrophy – macrodactyly JAAD 33:154–155, 1995

CORTICOTROPIN-INDEPENDENT CUSHING’S SYNDROME

Adrenocortical tumors

Adrenal carcinoma NEJM 332:791–803, 1995

Adrenocorticotropic hormone (ACTH) deficiency - breast hypertrophy J Endocrinol Invest 10:127–129, 1987 Adrenogenital syndrome – natal teeth; acne vulgaris Adrenoleukodystrophy (Siemerling-Creutzfeld disease) – diffuse hyperpigmentation Am J Hum Genet 27:547–553, 1975 APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy) syndrome (autoimmune polyendocrine syndrome type 1) – autosomal recessive; mutation in AIRE gene (autoimmune regulator gene); chronic mucocutaneous candidiasis, hypoparathyroidism, Addison’s disease, diabetes mellitus type 1, thyroid autoimmune disease, gonadal failure, hepatitis, vitiligo, alopecia areata, pernicious anemia, intestinal malabsorption, keratinopathy, dystrophy of dental enamel and nails JAAD 62:864–868, 2010; Beckwith-Wiedemann syndrome (Exomphalos-MacroglossiaGigantism) (EMG) syndrome – autosomal dominant; zosteriform rash at birth, exomphalos, macroglossia, visceromegaly, facial salmon patch of forehead, upper eyelids, nose, and upper lip and gigantism; linear earlobe grooves, circular depressions of helices; increased risk of Wilms’ tumor, adrenal carcinoma, hepatoblastoma, and rhabdomyosarcoma JAAD 37:523–549, 1997; Am J Dis Child 122:515–519, 1971 Carney complex – café au lait macules; myxoma (cutaneous and mucosal), blue nevus, epithelioid blue nevus, intense freckling, multiple skin tags, lipomas; pigmented nodular adrenocortical disease; thyroid, colon, pancreatic, ovarian carcinoma Ped Derm 36:160–162, 2019; BJD 164:245–256, 2011 Congenital adrenal hyperplasia - breast hypertrophy; clitoromegaly Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 108; non-classic congenital adrenal hyperplasia, 21-hydroxylase deficiency; PCOS-like Human Reprod Update 23:580–598, 2017 Cushing’s disease - Addisonian pattern of hyperpigmentation Ped Derm 15:253–258, 1998; oral pigmentation; Cushing’s syndrome – bilateral macronodular adrenal hyperplasia NEJM 369:2115–2125, 2013; NEJM 369:2105–2114, 2013; Cushing’s syndrome/disease – atrophic striae Semin Dermatol 3:287–294, 1984; bilateral mac-

Bilateral adrenocortical adenomas Surg Today 24:538–543, 1994 Cushing’s syndrome Ann Int Med 138:980–991, 2003; bilateral macronodular adrenal hyperplasia NEJM 369:2115–2125, 2013; NEJM 369:2105–2114, 2013 Familial Cushing’s syndrome – micronodular adrenocortical dysplasia Arch Int Med 148:1133–1136, 1988 Food dependent Cushing’s syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide NEJM 327:974–980, 1992; NEJM 327:981–986, 1992 Macronodular adrenal hyperplasia Endocrinol Jpn 36:101–116, 1989 Micronodular adrenal hyperplasia Endocrinol Jpn 36:101–116, 1989 Pigmented adenoma of the adrenal cortex Urology 7:641–645, 1976 Primary adrenocortical nodular hyperplasia associated with Carney complex J Clin Endocrinol Metab 82:1274–1278, 1997; Nippon Naibunpi Gakkai Zasshi 68:607–622, 1992

AINHUM TRUE AINHUM Dactylosis spontanea - ainhum NY State Med J 81:1779–1781, 1981; J Am Podiatr Assoc 61:44–54, 1971; Ann Trop Med Parasitol 55:314–320, 1961; Ann Surg 132:312–314, 1950 Familial ainhum JAMA 76:560, 1921

PSEUDOAINHUM JAAD 44:381–384, 2001

AUTOIMMUNE DISEASES CREST syndrome Lupus erythematosus, discoid J Dermatol 25:275–276, 1998

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Morphea Acta DV (Stockh) 76:162, 1996 Reynold’s syndrome – CREST syndrome and primary biliary cirrhosis JAAD 44:381–384, 2001 Rheumatoid arthritis Rheumatology 22:1–6, 1970 Scleroderma (progressive systemic sclerosis) JAAD 44:381–384, 2001; linear scleroderma AD 132:1520–1521, 1996

CONGENITAL DISORDERS Congenital pseudoainhum AD 105:434–438, 1972; Ulster Med J 34:99–102, 1965; to be differentiated from aplasia of the limbs with rudimentary digits, acromelia (part of limb does not develop), hypoplasia (poorly developed limb parts) Syringomyelia JAAD 44:381–384, 2001

EXOGENOUS AGENTS Hair/thread tourniquet syndrome (strangulation syndrome) Ped Derm 19:555–556, 1988; J Pediatr 69:136–138, 1966

INFECTIONS Leprosy JAAD 44:381–384, 2001 Syphilis, tertiary JAAD 44:381–384, 2001 Warts - bone destruction of distal phalanx AD 107:275–276, 1973 INFLAMMATORY DISORDERS Sarcoidosis - mutilating form AD 133:882–888, 1997

METABOLIC DISORDERS Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia JAMA Derm 149:969– 970, 2013; BJD 167:988–900, 2012 Diabetes mellitus; diabetic neuropathy – personal observation Erythropoietic porphyria

Loricrin keratoderma – ichthyosis, palmoplantar keratoderma, pseudoainhum BJD 159:714–719, 2008; Ped Derm 19:285–292, 2002 Mal de Meleda (keratosis palmoplantaris transgrediens et progressiens – constricting bands of terminal phalanges Cutis 93:193–198, 2014; Curr Prob Derm 14:71–116, 2002; Ped Derm 14:186–191, 1997; BJD 128:207–212, 1993; Dermatology 184:78– 82, 1992 Palmoplantar keratoderma, pseudoainhum (constriction bands), knuckle pads, hearing loss – mutation in GJB6 encoding connexin 30 BJD 161:452–455, 2009 Palmoplantar keratoderma of Gamborg Nielsen JAAD 44:381–384, 2001 Palmoplantar keratoderma of Sybert - autosomal dominant; autosomal dominant; palmoplantar erythema and keratoderma with transgrediens distribution, intertriginous hyperkeratosis, pseudoainhum with spontaneous amputations Curr Prob Derm 14:71–116, 2002; JAAD 44:381–384, 2001; JAAD 18:75–86, 1988 Papillon-Lefevre syndrome JAAD 51:S134–136, 2004 Pityriasis rubra pilaris Actas Dermosifiliogr 64:245–248, 1974 Progressive symmetric erythrokeratoderma Am J Hum Genet 61:581–589, 1997 Psoriasis BJD 149:1064–1066, 2003; JAAD 7:130–132, 1982 Vohwinkel’s syndrome (keratoderma hereditaria mutilans) – autosomal dominant; honeycomb palmoplantar keratoderma, hyperkeratotic knuckle papules with starfish keratoses; ichthyosis, pseudoainhum; JAAD 44:376–378, 2001; with congenital sensorineural deafness – mutation in GJB2 (connexin 26) (gap junction protein), D66H; or loricrin mutations BJD 164:197–199, 2011; Clinics in Dermatol 23:23–32, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 44:376–378, 2001; BJD 145:657–660, 2001; Hum Mol Genet 8:1237–1243, 1999; loricrin mutation JID 111:702–704, 1998; Nat Genet 13:70–77, 1996; Hautarzt 44:738–741, 1993 Vorner’s palmoplantar keratoderma – epidermolytic PPK, knuckle pads and digital mutilation; KRT9 mutation BJD 165:199–201, 2011

PSYCHOCUTANEOUS SYNDROMES Factitial dermatitis Plica neuropathica, hair matting, schizophrenia Cutis 28:629–630, 1981

Erythropoietic protoporphyria BJD 118:113–116, 1988

SYNDROMES

NEOPLASTIC DISEASES

Adams-Oliver syndrome - personal observation

Porokeratosis of Mibelli Cutis 49:129–130, 1992; loss of distal phalanges (mutilation) Cutis 86:77–80, 2010

Amnion rupture malformation sequence (congenital ring constrictions and intrauterine amputations; amniotic band syndrome); after amniocentesis Int J Dermatol 27:312–314, 1988

PRIMARY CUTANEOUS DISEASES Acral keratoderma JAAD 44:381–384, 2001 Epidermolysis bullosa, dominant dystrophic, recessive dystrophic personal observation Harlequin fetus (harlequin ichthyosis) – constrictions BJD 174:689– 691, 2016; Ped Derm 31:625–629, 2014 Keratosis palmoplantaris (Unna-Thost type?) with polydactyly and eosinophilia Dermatologica 138:39–44, 1969 Lamellar ichthyosis Ped Derm 21:181, 2004; Ann DV 128:1037– 1039, 2001

Autosomal recessive ectodermal dysplasia with cataracts, alopecia, and sclerodactyly Am J Hum Genet 32:500–503, 1989 Buschke-Fischer-Brauer keratoderma (punctate palmoplantar keratoderma) (keratodermia palmo-plantaris papulosa) (keratodermia palmoplantare papuloverrucoides progressiva) (keratosis hereditarium dissipatum palmare et plantare) - clinical subtypes include pinhead papules, spiky filiform lesions, dense round 1–2mm papules, clavus-like lesions, hard warty masses, cupuliform lesions, and focal translucent lesions BJD 128:104–105, 1993; JAAD 8:700–702, 1983; Hum Genet 60:14–19, 1982; with ainhum Actas Dermosifiliogr 73:105–110, 1982 Carpal tunnel syndrome BJD 150:166–167, 2004

Alopecia and Structural Abnormalities of the Nose and Hands Clouston’s disease Int J Dermatol 29:225–226, 1990

TOXINS

Congenital ichthyosiform dermatosis with linear keratotic flexural papules and sclerosing palmoplantar keratoderma AD 125:103– 106, 1989

Alcoholic toxic polyneuropathy Z Hautkr 55:349–354, 1980

Congenital sensory neuropathy with anhidrosis Ped Derm 11:231– 236, 1994; JAAD 21:736–739, 1989 Dermatopathia pigmentosa reticularis hyperkeratosis et mutilans – infantile bullae, reticular hyperpigmentation of flexures, punctate palmoplantar keratoderma, ainhum-like contraction, periodontopathy Ehlers-Danlos syndrome Epidermal nevus syndrome Ped Derm 349–352, 2002 Focal acral hyperkeratosis and angiodysplasia with pseudoainhum J R Soc Med 78 (Supp 11)13–15, 1985 Hereditary sensory and autonomic neuropathy Type II JAAD 21:736–739, 1989 Kindler’s syndrome (hereditary bullous acrokeratotic poikiloderma of Weary-Kindler) (hereditary bullous acrokeratotic poikiloderma of Weary-Kindler) – constriction bands of fingers Ped Derm 35:864– 865, 2018; poor dentition and premature loss of teeth due to periodontitis, gingivitis; teeth enamel defects; bullous disease in infancy, photosensitivity, poikiloderma, atrophic skin of dorsal hands, pseudoainhum; erythroderma, palmoplantar keratoderma, red elbows and knees; mutation in FERMT1 gene BJD 159:1192–1196, 2008; BJD 158:1375–1377, 2008; Ped Derm 23:586–588, 2006; AD 142:1619–1624, 2006; AD 142:620–624, 2006; AD 140:939–944, 2004; Int J Dermatol 36:529–533, 1997; AD 1487–1490, 1996; BJD 66:104–111, 1954 KLICK syndrome (keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – autosomal recessive; polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; BJD 153:461, 2005; Am J Hum Genet 61:581–589, 1997; Acta DV 77:225–227, 1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989 Olmsted syndrome BJD 174:209–211, 2016; Ped Derm 21:603– 605, 2004; Ped Derm 20:323–326, 2003; BJD 136:935–938, 1997; AD 132:797–800, 1996; AD 131:738–739, 1995; JAAD 10:600–610, 1984

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Ergot poisoning JAAD 44:381–384, 2001

TRAUMA Amniocentesis Burns JAAD 44:381–384, 2001 Cold injury – frostbite JAAD 44:381–384, 2001 Physical trauma JAAD 44:381–384, 2001 Post-traumatic scars Ped Derm 19:555–556, 2002 Umbilical artery catheterization (unintentional) – anonychia, hyponychia, and spontaneous amputation of distal phalanges due to ischemic necrosis BJD 157:1299–1301, 2007

VASCULAR DISORDERS Arteriovenous malformation Raynaud’s phenomenon JAAD 44:381–384, 2001

 LOPECIA AND STRUCTURAL A ABNORMALITIES OF THE NOSE AND HANDS Alopecia-onychodysplasia-hypohidrosis-deafness syndrome – small teeth, thick dystrophic toenails, hypohidrosis, hyperkeratosis of palms and soles, elbows and knees, sensorineural deafness Human Hered 27:127–337, 1977 Ankyloblepharon, ectodermal dysplasia, cleft lip/palate with ectrodactyly (AEC) syndrome – diffuse erythema with fine scaling and shallow erosions; no scalp hair or eyebrows or eyelashes; ectropion and ankyloblepharon; low set ears, broad and beaked nose; downturned mouth; ectrodactyly of right foot, choanal stenosis; erosive scalp and diaper dermatitis Ped Derm 28:15–19, 2011 Chondroectodermal dysplasia (Ellis van Creveld syndrome) Ped 26:301–309, 1960

Pachyonychia congenita JAAD 44:381–384, 2001

Clouston’s syndrome

Simonart syndrome Hautarzt 54:163–166, 2003

Coffin-Siris syndrome Am J Dis Child 119:433–439, 1970

STING-associated vasculopathy with onset in infancy (SAVI) (type 1 interferonopathy) – red plaques of face and hands; chilblain-like lesions; atrophic plaques of hands, telangiectasias of cheeks, nose, chin, lips, acral violaceous plaques and acral cyanosis (livedo reticularis of feet, cheeks, and knees), distal ulcerative lesions with infarcts (necrosis of cheeks and ears), gangrene of fingers or toes with ainhum, reticulate erythema of arms and legs; nasal septal perforation, nail dystrophy; small for gestational age; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis with ground glass and reticulate opacities; gain of function mutation in TMEM173 (stimulator of interferon genes); mimics granulomatosis with polyangiitis JAAD 74:186–189, 2016; JAMA Derm 151:872–877, 2015; NEJM 371:507–518, 2014

GAPO syndrome - growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy; midface hypoplasia; frontal bossing, wide anterior fontanelle, saddle nose, protruding thick lips, low set ears, anti-Mongoloid slant, diffuse scalp hypotrichosis, prominent scalp veins, sparse eyebrows and eyelashes, absent teeth, slightly redundant skin, impacted teeth Ped Derm 27:156–161, 2010; Ped Derm 19:226, 2002; J Craniofac Genet Dev Biol 19:189–200, 1999; Birth Defects 24:205–207, 1988; Am J Med Genet 19:209– 216, 1984; Syndr Ident 8:14–16, 1982; Odont Tilster 55:484–493, 1947

Woolly hair and striate palmoplantar keratoderma - mutation in KANK2; leukonychia, pseudoainhum of 5th toe; no cardiac abnormalities Ped Derm 34:724–725, 2017

Hidrotic ectodermal dysplasia (Clouston’s syndrome) J Can Med Ass 21:18–31, 1929 Langer-Gideon syndrome Orthop Rev 21:31–35, 1992 Larsen’s syndrome J Ped 37:574–581, 1950 Neu-Laxova syndrome - resembles harlequin fetus; resembles restrictive dermopathy Oral facial digital syndrome Arch Dis Child 44:729–731, 1969

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Pure hair and nail ectodermal dysplasia, autosomal recessive – hypotrichosis, dystrophic nails; HOXC13 Ped Derm 34:172–175, 2017 Trichoonychodental dysplasia Oral Surg 46:376–385, 1978 Trichorhinophalangeal syndrome types I, II, III JAAD 31:331–336, 1994

ALOPECIA, EYEBROWS

papules, thickened skin, eyebrow alopecia, leonine facies; madarosis of eyebrows; cobblestoning of nose, forehead, and glabella acneiform eruptions; inflammatory papules and pustules JID 139:255–292, 2019; AD 148:726–733, 2012; AD 146:871–874, 2010; Ped Derm 27:509–513, 2010; JAAD 60:169–172, 2009; J Cutan Pathol 34:721–725, 2007; AD 142:1643–1648, 2006; Am J Surg Pathol 29:241–246, 2005; JAAD 52:540–541, 2005; JAAD 50:310–315, 2004; JAAD 50:318–322, 2004;JAAD 43:118–122, 2000; J Invest Dermatol Symp Proc 4:268–271, 1999; Hautarzt 46:871–874, 1995

AUTOIMMUNE DISEASES

INFILTRATIVE LESIONS

Alopecia areata NEJM 366:1515–1525, 2012; JAAD 62:177–188, 2010; Int J Derm 37:617–621, 1998

Alopecia mucinosa (follicular mucinosis) BJD 163:420–423, 2010;

Lupus erythematosus - discoid lupus erythematosus NEJM 269:1155–1161, 1963 Morphea – including linear morphea (en coup de sabre) Rook p. 2504–2508, 1998, Sixth Edition

Dermatology 197:178–180, 1998; AD 125:287–292, 1989; JAAD 10:760–768, 1984; AD 76:419–426, 1957

INFLAMMATORY DISORDERS Folliculitis decalvans

CONGENITAL DISORDERS Aplasia cutis congenita

Sarcoidosis - personal observation

Amniotic adhesions

METABOLIC DISORDERS

Cutaneous trauma

Hypoparathyroidism, idiopathic

Epidermolysis bullosa Focal dermal hypoplasia

Hypothyroidism (myxedema) – loss of lateral eyebrows JAAD 26:885–902, 1992

Intrauterine infection

Hyperthyroidism

Intrauterine or perinatal trauma Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis Ped Derm 29:756–758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985

DRUGS Cyclosporine-induced folliculodystrophy – partial alopecia of eyebrows and eyelashes JAAD 50:310–315, 2004

EXOGENOUS AGENTS Cocaine – crack cocaine; madarosis JAAD 69:135–142, 2013; NEJM 314:1324, 1986

INFECTIONS Leprosy – lepromatous with leonine facies JAMA Derm 153:313– 314, 2017; tuberculoid Syphilis - secondary Sex Transm Dis 9:43–44, 1982 Tinea faciei

NEOPLASTIC DISEASES Keratoacanthomas – Grzybowski eruptive keratoacanthomas BJD 147:793–796, 2002 Leukemia cutis Krygowski 103:212, 2019 Lymphoma - cutaneous T-cell lymphoma; CD4+ small to medium size pleomorphic T-cell lymphoma – red swollen eyelid with alopecia of eyebrow Ped Derm 30:595–599, 2013

PHOTODERMATOSES Actinic prurigo – cheilitis, conjunctivitis, eyebrow alopecia, dermatitis, facial scars JAAD 67:1093–1110, 2012 BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981 Chronic actinic dermatitis – acute, subacute, or chronic dermatitis with lichenification, papules, plaques, erythroderma, stubby scalp and eyebrow hair AD 136:1215–1220, 2000; AD 130:1284–1289, 1994; JAAD 28:240–249, 1993; AD 126:317–323, 1990; sensitization by sesquiterpene lactone mix BJD 132:543–547, 1995; associated with musk ambrette Cutis 54:167–170, 1994; JAAD 3:384–393, 1980 Polymorphous light eruption - suboccipital actinic alopecia and actinic madurosis Int J Dermatol 30:375–376, 1991

Tuberculosis – lupus vulgaris Trichodysplasia spinulosa(trichodysplasia of immunosuppression) (viral-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy) – DNA polyoma virus in renal transplant patient; alopecia, particulate matter, follicular

PRIMARY CUTANEOUS DISEASES Acne necrotica varioliformis BJD 160:482–501, 2009 Atopic dermatitis – Hertoghe’s sign

Alopecia, Eyebrows Autosomal recessive hypotrichosis simplex – mutations in desmoglein 4, phospholipase H (LIPH), and 6 protein coupled receptor (P2RY5); sparse to absent scalp hair, eyebrows, and eyelashes, axillary, and body hair; normal beard BJD 160:1006–1010, 2009; BJD 160:194–196, 2009 Epidermolysis bullosa – GABEB (generalized atrophic benign epidermolysis bullosa) BJD 138:859–866, 1998; polydysplastic Erythroderma Frontal fibrosing alopecia JAAD 79:789–804, 2018; BJD 175:1099– 1101, 2016; JAAD 70:670–678, 2014; BJD 166:208–210, 2012; BJD 166:440–442, 2012; JAAD 63:653–660, 2010; JAAD 52:55–60, 2005; AD 130:770–774, 1994 Keratosis lichenoides chronica - in children JAAD 56:S1–5, 2007 Keratosis follicularis spinulosa decalvans BJD 160:482–501, 2009 Lamellar ichthyosis Lichen simplex chronicus (neurodermatitis) Marie-Unna hereditary hypotrichosis – autosomal dominant; sparse curly hair; begins at puberty; at vertex; starts affects eyebrows, eyelashes, body and pubic hair; 50% with widely spaced incisors; 8p21 JAMA Derm 150:567–568, 2014; Ped Derm 28:202–204, 2011; BJD 160:194–196, 2009; Ped Derm 19:250–252, 2002; Derm Wschr 82:1167–1178, 1925 Monilethrix JAAD 59:1–22, 2008; AD 132:577–578, 1996 Pili torti – isolated defect Cutis 84:143–147, 2009; Rook p. 2947– 2948, 1998, Sixth Edition; Acta DV 53:385–392, 1973; associated with Menkes’ kinky hair syndrome Ann DV 102:269–271, 1980; Pediatrics 50:181–183, 1972; Pediatrics 29:764–779, 1962; Beare syndrome BJD 64:366–372, 1952; Bjornstad’s syndrome Eur J Dermatol 10:91–97, 2000; Bazex syndrome, Crandall’s syndrome, Rapp-Hodgkin syndrome J Med Genet 5:269–272, 1968; trichodysplasia-xeroderma Clin Genet 31:337–342, 1987; trichothiodystrophy AD 116:1375–1384, 1980; hidrotic ectodermal dysplasia, pseudomonilethrix, oral retinoids Cutis 35:466–470, 1985; anorexia nervosa Cutis 57:151–152, 1996 Pseudomonilethrix – trauma with artefactual microscopic appearance AD 122:688–692, 1986 Psoriasis Ulerythema oophyrogenes (keratosis pilaris atrophicans) Cutis 93:83–87, 2014; Rook p. 2936, 1998, Sixth Edition   Cardiofaciocutaneous syndrome   Cornelia de Lange syndrome   Noonan syndrome   Rubinstein-Taybi syndrome

PSYCHOCUTANEOUS DISEASES Factitial dermatitis Trichotillomania Curr Prob in Derm VIII:97–136, 1996; Aust NZ J Ophthalmol 23:59–61, 1995; J Clin Psychol Psychiatry 32:401–409, 1991

SYNDROMES Ablepharon-macrostomia syndrome - absent eyelids, eyebrows, and eyelashes at birth Br J Ophthalmol 25:317–319, 1991 AEC syndrome (Hay-Wells syndrome) - ankyloblepharon, ectodermal dysplasia, cleft lip/palate syndrome – blepharitis, eyelid papillomas, periorbital wrinkling; microcephaly, widespread congenital scalp erosions; alopecic ulcerated plaques of scalp, trunk, groin; alopecia of scalp and eyebrows; congenital erythroderma; depig-

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mented patches; syndactyly; bony abnormalities; widely spaced nipples; TP63 mutation Ped Derm 28:15–19, 2011; Ped Derm 26:617–618, 2009; AD 141:1591–1594, 2005; AD 141:1567–1573, 2005; AD 134:1121–1124, 1998; Ped Derm 14:149–150, 1997; BJD 94:287–289, 1976; generalized fissured erosions of trunk BJD 149:395–399, 2003; Textbook of Neonatal Dermatology, p.468, 2001; TP63 mutations seen in AEC syndrome, EEC syndrome, RappHodgkin syndrome, limb-mammary syndrome, split-hand split-foot malformation type 4, acro-dermatoungual-­lacrimal-tooth syndrome AD 141:1567–1573, 2005 Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) J Dermatol 26:44–47, 1999; X-linked recessive – premature aged appearance with soft, dry, finely wrinkled skin, especially around eyes; absent or reduced sweating, hypotrichosis, and total or partial anodontia J Med Genet 28:181–185, 1991; autosomal recessive Ped Derm 7:242, 1990 Apert’s syndrome – interrupted eyebrows Cutis 52:205–208, 1993 Atrichia congenita Atrichia with papular lesions JAAD 47:519–523, 2002 Multiple basaloid follicular hamartoma syndrome J Dermatol 23:821–824, 1996 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Syndrome Ident 8:6–9, 1982 Basan syndrome - sparse coarse scalp hair, hypohidrosis, nail dystrophy, abnormal dermatoglyphics, dental abnormalities Arch Klin Exp Dermatol 222:546–557, 1965 Bazex-Dupre-Christol-like syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Ped Derm 23:286–290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Cardio-facio-cutaneous syndrome (Noonan-like short stature syndrome) – autosomal dominant, acanthosis nigricans, xerosis/ ichthyosis, eczematous dermatitis, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, lentigines, nevi of palms and soles, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly short scalp hair and eyebrows and lashes, temporal alopecia, palmoplantar keratoderma of pressure points, hemangiomas, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects BJD 180:172–180, 2019; JAAD 46:161–183, 2002; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992; JAAD 22:920–922, 1990 Cartilage hair hypoplasia syndrome J Med Genet 32:39–43, 1995 Centrofacial trichoblastomatosis – leonine facies, cobblestoning of glabella and nose, eyebrow alopecia BJD 169:224–226, 2013 Chromosome 4 deletion syndrome Congenital hypotrichosis Int J Derm 38 (Suppl 1):25–33, 1999

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CRIE syndrome - congenital reticulated ichthyosiform erythroderma – formerly ichthyosis en confetti (includes ichthyosis variegate, MAUIE syndrome); minor criteria include collodion membrane, nail dystrophy, large lunulae, palmoplantar hyperkeratosis, ectropion, strabismus, nystagmus, joint contractures, small weight and length; decreased finger length, decreased eyebrows and eyelashes JAMA Derm 151:64–69, 2015; JAMA Derm 151:15–16, 2015; Acta DV 94:579–582, 2014; Dermatology 188:40–45, 1994 Dermatopathia pigmentosa reticularis – autosomal dominant; reticulate pigmentation of trunk, neck, and proximal extremities, alopecia, nail changes (mild onychodystrophy), palmoplantar hyperkeratosis, loss of dermatoglyphics, hyperpigmented tongue, hypo- or hyperhidrosis, non-scarring blisters of dorsal hands and feet, dark areolae, thin eyebrows, Ped Derm 24:566–570, 2007; J Dermatol 24:266–269, 1997; JAAD 26:298–301, 1992; AD 126:935–939, 1990; Dermatol Wochenschr 138:1337, 1958

Familial hypoplasia of the eyebrows Focal facial dermal dysplasia with other facial anomalies (Setleis syndrome) – leonine aged facies with absent eyelashes, eyebrows, puckered periorbital skin, scar-like defects of temples AD 110:615– 618, 1974 GAPO syndrome - growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy; midface hypoplasia; frontal bossing, wide anterior fontanelle, saddle nose, protruding thick lips, low set ears, anti-Mongoloid slant, diffuse scalp hypotrichosis, prominent scalp veins, sparse eyebrows and eyelashes, absent teeth, slightly redundant skin, impacted teeth Ped Derm 27156–161, 2010; Ped Derm 19:226, 2002; J Craniofac Genet Dev Biol 19:189–200, 1999; Birth Defects 24:205–207, 1988; Am J Med Genet 19:209– 216, 1984; Syndr Ident 8:14–16, 1982; Odont Tilster 55:484–493, 1947

Down’s syndrome

Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa, thin eyebrows, corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005

Dubowitz syndrome – autosomal recessive, erythema and scaling of face and extremities in infancy, sparse blond scalp and eyebrow hair, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities Am J Med Genet 63:277– 289, 1996; Am J Med Genet 47:959–964, 1993

Hallerman-Streiff syndrome – pinched beak nose, extraordinary retrognathia, parrot-like appearance, frontal and/or occipital bossing, atrophy of skin especially of nose, proportionate dwarfism, microphthalmos, cataracts, sparse eyebrows and eyelashes Clin Exp Dermatol 29:477–479, 2004

Ectodermal dysplasia – ankyloblepharon, absent lower eyelashes, hypoplasia of upper lids, coloboma, seborrheic dermatitis, cribriform scrotal atrophy, ectropion, lacrimal duct hypoplasia, malaligned great toenails, gastroesophageal reflux, ear infections, laryngeal cleft, dental anomalies, scalp hair coarse and curly, sparse eyebrows, xerosis, hypohidrosis, short nose absent philtrum, flat upper lip BJD 152:365–367, 2005

Happle syndrome - cicatricial alopecia - X-linked dominant erythrodermic ichthyosis at birth, cataracts, generalized follicular atrophoderma, asymmetric shortening of limbs with chondrodysplasia punctata Ped Derm 18:442–444, 2001; Ped Derm 13:1–4, 1996

Ectodermal dysplasia with pili torti and syndactyly – sparse hair, eyebrows and lashes, severe dental dysplasia, yellow thickened nails, lordosis, high arched palate, and syndactyly Ped Derm 16:220–221, 1999 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Ectrodactyly-ectodermal dysplasia-clefting syndrome – alopecia of scalp, eyebrows, and eyelashes, xerosis, atopic dermatitis, nail dystrophy, hypodontia with peg shaped teeth, reduced sweat glands and salivary glands, syndactyly, mammary gland and nipple hypoplasia, conductive or sensorineural hearing loss, urogenital anomalies, lacrimal duct abnormalities; TP63 mutations BJD 162:201–207, 2010 Encephalocraniocutaneous lipomatosis - alopecia, scalp nodules, skin-colored nodules, facial and eyelid papules - lipomas and lipofibromas; unilateral or bilateral skin-colored or yellow domed papules or nodules of scalp (hairless plaque), head, and neck; ipsilateral cranial and facial asymmetry, cranial and ocular abnormalities, spasticity, mental retardation Ped Derm 23:27–30, 2006; JAAD 37:102–104, 1998; JAAD 32:387–389, 1995; Ped Derm 10:164–168, 1993; Arch Neurol 22:144–155, 1970

Hereditary focal transgressive palmoplantar keratoderma – autosomal recessive; hyperkeratotic lichenoid papules of elbows and knees, psoriasiform lesions of scalp and groin, spotty and reticulate hyperpigmentation of face, trunk, and extremities, alopecia of eyebrows and eyelashes BJD 146:490–494, 2002 Hidrotic ectodermal dysplasia (Clouston syndrome) – alopecia of outer two-thirds of eyebrows; thin eyelashes Rook p.394, 1998, Sixth Edition; Can Med Assoc J 21:18–31, 1929 Hutchinson-Gilford syndrome (progeria) – sparse or absent eyelashes and eyebrows Am J Med Genet 82:242–248, 1999; J Pediatr 80:697–724, 1972 Ichthyosis-cheek-eyebrow syndrome - ICE syndrome – ichthyosis vulgaris, fullness of cheeks, thinning of eyebrows; dysmorphic features, skeletal anomalies Clin Genet 31:137–142, 1987 Ichthyosis follicularis with atrichia and photophobia (IFAP) – collodion membrane and erythema at birth; generalized follicular keratoses, non-scarring alopecia, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis; mutation in MBTPS2 (membrane-bound transcription factor peptidase, site 2) (zinc metalloproteinase) BJD 163:886–889, 2010; JAAD 46:S156–158, 2002; Am J Med Genet 85:365–368, 1999 AD 125:103–106, 1989; Dermatologica 177:341–347, 1988 Ichthyosis, follicular atrophoderma, eyebrow hypotrichosis, woolly hair BJD 147:604–606, 2002; Am J Med Genet 75:186–189, 1998 Incontinentia pigmenti JAAD 47:169–187, 2002; AD 116:701–703, 1980 Kabuki makeup syndrome (Niikawa-Kuroki syndrome) – short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperexten-

Alopecia, Eyebrows sible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly; preauricular dimple/fistula World J Ped 15:328–352, 2019; Orphanet J Rare Dis 14:255, 2019; Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 570–573, 1981 Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, follicular occlusion triad, scalp cysts, nodules (trichilemmal tumors, squamous cell carcinoma), bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation JAAD 69:127–134, 2013; Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; JAAD 19:1124– 1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915 Keratosis follicularis spinulosa decalvans (Siemens syndrome) – scarring alopecia of scalp and eyebrows; conjunctivitis; keratosis pilaris, follicular atrophoderma, facial erythema, scarring alopecia, ulerythema oophyrogenes, photophobia JAAD 58:499–502, 2008; AD 119:22–26, 1983; Arch Dermatol Syphilol 151:384–387, 1926 Koraxitrachitic syndrome – self-healing collodion baby; heals with mottled reticulated atrophy; alopecia, absent eyelashes and eyebrows, conjunctival pannus, hypertelorism, prominent nasal root, large mouth, micrognathia, brachydactyly, syndactyly of interdigital spaces Am J Med Genet 86:454–458, 1999 Leprechaunism (Donohue’s syndrome) – decreased subcutaneous tissue and muscle mass, characteristic facies, severe intrauterine growth retardation, broad nose, low set ears, hypertrichosis of forehead and cheeks, loose folded skin at flexures, gyrate folds of skin of hands and feet; breasts, penis, and clitoris hypertrophic Endocrinologie 26:205–209, 1988 Lipoid proteinosis Marie Unna’s hereditary hypotrichosis (hereditary hypotrichosis simplex) – autosomal dominant;, coarse sparse scalp hair and eyebrows; progressive coarsening JAMA Derm 150:567–568, 2014; Am J Med Genetics A 152:A:2628–2633, 2010; JAAD 59:1–22, 2008; BJD 150:837–842, 2004; Ped Derm 19:250–255, 2002; Ped Derm 19:148–150, 2002; BJD 143:811–814, 2000; Dermatology 196:339–342, 1998; Dermatology 191:139–141, 1995; Clin Genet 32:120–124, 1987; JID 57:389–400, 1971 Meige syndrome - conjunctival edema and alopecia of the lateral third of the eyebrow Graefes Arch Clin Exp Ophthalmol 238:98–100, 2000 Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation (nevus depigmentosus); small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Neonatal ichthyosis sclerosing cholangitis syndrome (NISCH) – autosomal recessive; sparse scalp hair, lamellar ichthyosis, thin eyelashes and eyebrows; mutation in CLDN1 gene (claudin) (tight

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junction protein); teeth anomalies, mental retardation bilateral uveal synechiae BJD 170:976–978, 2014 Netherton’s syndrome Ped Derm 13:183–199, 1996 Noonan’s syndrome Sem Derm 14:140–144, 1995 Oculo-dento-osseous dysplasia – sparse scalp hair, eyebrows and eyelashes sparse or absent, small closely set sunken eyes, small mouth, enamel hypoplasia producing yellow teeth, syndactyly, camptodactyly, iris anomalies, hypertelorism J Pediatr 63:69–75, 1963 Oculomandibular dysostosis Oculovertebral dysplasia Omenn syndrome (familial reticuloendotheliosis with eosinophilia) – autosomal recessive; neonatal exfoliative erythroderma, subacute combined immunodeficiency, diarrhea, hepatosplenomegaly, alopecia of scalp and eyebrows, failure to thrive, lymphadenopathy BJD 158:1153–1156, 2008; AD 136:875–880, 2000; Ped Derm 17:91–96, 2000; Ped Derm 14:49–52, 1997; JAAD 25:442–446, 1991 Popliteal pterygium syndrome Progeria Rapp-Hodgkin hypohidrotic ectodermal dysplasia - autosomal dominant; alopecia of wide area of scalp in frontal to crown area, short eyebrows and eyelashes, coarse wiry sparse hypopigmented scalp hair, sparse body hair, scalp dermatitis, ankyloblepharon, syndactyly, nipple anomalies, cleft lip and/or palate; nails narrow and dystrophic, small stature, hypospadias, conical teeth and anodontia or hypodontia; distinctive facies, short stature JAAD 53:729–735, 2005; Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968 ROMBO syndrome - hypotrichosis of eyebrows BJD 144:1215– 1218, 2001 Rothmund-Thomson syndrome – poikiloderma, photosensitivity (early erythema, edema, blistering of face); sparse hair, sparse eyebrows and eyelashes, small stature, palmoplantar keratoderma, skeletal anomalies, cataracts; osteosarcoma in 30%; JAAD 75:855–870, 2016; JAAD 67:1113–1127, 2012; Curr Prob Derm 14:41–70, 2002; BJD 139:1113–1115, 1998; Ped Derm 6:325–328, 1989; Ped Derm 6:321–324, 1989; JAAD 17:332–338, 1987; mutations in DNA helicase gene RECQL4 Nat Genet 22:82–84, 1999; Arch Ophthalmol (German) 4:159, 1887 Tietz’s syndrome – autosomal dominant; absence of pigment, deaf-mutism, hypoplastic eyebrows Am J Hum Genet 15:259–264, 1963 Trichodental syndrome – fine short hair, madurosis BJD 116:259– 263, 1987 Trichorhinophalangeal syndrome type I – autosomal dominant; slow growing hair, receding frontotemporal hairline with high bossed forehead; thin nails, koilonychias, leukonychia, facial pallor, pear-shaped nose with bulbous nose tip, wide long philtrum, thin upper lip, triangular face, receding chin, tubercle of normal skin below the lower lip, protruding ears, distension and deviation with fusiform swelling of the PIP joints; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, lateral eyebrows sparse and brittle,, dense medially, bone deformities (hands short and stubby), cone-shaped epiphyses of bones of hand, lateral deviation of interphalangeal joints, flat feet, hip malformations, high arched palate, supernumerary teeth, dental malocclusion, mild short stature; hypotonia, deep voice, recurrent respiratory infections, hypoglycemia, diabetes mellitus, hypothyroidism, decreased growth hormone, renal and cardiac defects, mutation in zinc finger nuclear transcription factor (TRPS1 gene) Cutis 89:56,73–74, 2012; BJD 163:416–419, 2010; Ped Derm 26:171–175, 2009; Ped Derm

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25:557–558, 2008; BJD 157:1021–1024, 2007; AD 137:1429–1434, 2001; JAAD 31:331–336, 1994; Hum Genet 74:188–189, 1986; Helv Paediatr Acta 21:475–482, 1966 Trichorhinophalangeal syndrome type II (Langer-Giedion syndrome) – microcephaly with mental retardation, deep set eyes, exotropia, long nose with bulbous tip, broad nasal bridge, thick ala nasi, high palate, crowded teeth, micrognathia, long neck, short metacarpals, thin nails, small feet with brachydactyly, vaginal stenosis, short stature, thin sparse hair, long face, prominent ears, madarosis, cartilaginous exostoses, foot deformities, joint laxity; EXT gene BJD 171:1581–1583, 2014; BJD 157:1021–1024, 2007 Trichothiodystrophy syndromes (Tay syndrome) - BIDS, IBIDS, PIBIDS – autosomal recessive; collodion baby, congenital erythroderma, sparse or absent eyelashes and eyebrows, sulfur deficient short brittle hair with tiger tail banding on polarized microscopy, trichomegaly, brittle soft nails with koilonychia, premature aging, very short stature, microcephaly, sexual immaturity, ichthyosis, photosensitivity, hypohidrosis, high arched palate, dysmyelination of white matter, bird-like facies, abnormal teeth with dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; recurrent infections with neutropenia; ocular abnormalities, osteopenia; socially engaging personality; mutation in one of 3 DNA repair genes (XPB, XPA, TTDA, or TTDN1 JAAD 63:323–328, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Pediatrics 87:571–574, 1991; Am J Med Genet 35:566–573, 1990; JAAD 16:940–947, 1987; Eur J Pediatr 141:147–152, 1984 Trisomy 18 (Edward’s syndrome) Orphanet J Rare Dis 2012 Woodhouse-Sakati syndrome – autosomal recessive; triangular shaped face with prominent forehead, large low set ears, dystonia, hypotrichosis, with sparse eyebrows and eyelashes; alopecia, hypogonadism, diabetes mellitus, mental retardation, sensorineural deafness, extrapyramidal signs, low insulin-like growth factor 1; must be differentiated from congenital hypotrichosis; mutation in C2orf37 Ped Derm 31:83–87, 2014; Am J Med Genet 143:149–160, 2007; J Med Genet 20:216–219, 1983

TRAUMA Burns – chemical, thermal Radiation

 LOPECIA IN NEONATES, INFANTS, A AND TODDLERS Acrodermatitis enteropathica - periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche JAAD 56:116–124, 2008; Ped Derm 19:426–431, 2002 AEC syndrome (Hay-Wells syndrome) - ankyloblepharon, ectodermal dysplasia, cleft lip/palate syndrome – sparse wiry hair with patchy scarring alopecia; blepharitis, eyelid papillomas, periorbital wrinkling; microcephaly, widespread congenital scalp erosions; alopecic ulcerated plaques of scalp, trunk, groin; alopecia of scalp and eyebrows; congenital erythroderma; depigmented patches; syndactyly; bony abnormalities; widely spaced nipples; TP63 mutation Ped Derm 28:313–317, 2011; Ped Derm 26:617–618, 2009; AD 141:1591–1594, 2005; AD 141:1567–1573, 2005; AD 134:1121–1124, 1998; Ped Derm 14:149–150, 1997; generalized fissured erosions of trunk BJD 149:395–399, 2003; TP63 mutations

seen in AEC syndrome, EEC syndrome, Rapp-Hodgkin syndrome, limb-­mammary syndrome, split-hand split-foot malformation type 4, acro-dermatoungual-lacrimal-tooth syndrome AD 141:1567–1573, 2005 Alopecia-mental retardation syndrome BJD 159:748–751, 2008 Alopecia mucinosa of scalp BJD 157:609–610, 2007 Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) J Dermatol 26:44–47, 1999; X-linked recessive – absent or reduced sweating, hypotrichosis, and total or partial anodontia with conical pointed teeth J Med Genet 28:181–185, 1991; autosomal recessive Ped Derm 7:242, 1990; mutation in ectodysplasin A (TNF family) Ped Derm 23:396–398,2006 Aplasia cutis congenita   Differential diagnosis – congenital herpes simplex virus, varicella zoster virus, staphylococcal scalded skin syndrome, epidermolysis bullosa, incontinentia pigmenti, Goltz’s syndrome, pemphigoid gestations, pemphigus vulgaris, pemphigus foliaceus, congenital vesicular and erosive dermatosis with supple and reticulated scarring JAAD 69:909–915, 2013; AD 121:361–367, 1985 Arthrogryposis, renal tubular dysfunction, and cholestasis (ARC) syndrome – ichthyosis, scarring alopecia, ectropion, arthrogryposis of wrist, knee, and hip Ped Derm 22:539–542, 2005 Atrichia with papular lesions JAAD 47:519–523, 2002 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Syndrome Ident 8:6–9, 1982 Bazex-Dupre-Christol syndrome (X-linked dominant) - milia and comedo-like papules, congenital hypotrichosis, anhidrosis, X-linked dominant, follicular (vermiculate) atrophoderma of the face, elbows and hands, hypohidrosis, basal cell nevi and basal cell carcinomas, trichoepitheliomas, pinched nose, keratosis pilaris, scrotal tongue, joint hypermobility; UBE 2A gene Ped Derm 28:727–728, 2011; Ped Derm 25:112–113, 2008; Ped Derm 23:149–151, 2006; BJD 153:682–684, 2005; Dermatol Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999;JAAD 39:853–857, 1998; AD 130:337–342, 1994; Hautarzt 44:385–391, 1993; J Cutan Pathol 18:20–27, 1991; Ann Dermatol Syphilgr (Paris) 93:241–254, 1966; Bull Soc Franc Derm Syph 71:206, 1964 BDC syndrome – hypotrichosis early in life; must be differentiated from hypotrichosis simplex and hypohidrotic ectodermal dysplasia BJD 201–203, 2011 Cardiofaciocutaneous syndrome – brittle, dark, sparse curly hair; increased numbers of melanocytic nevi; characteristic facies with thick facial appearance, broad nose, frontal bossing, ulerythema ophryogenes, sparse eyebrows; 1–2 café au lait macules; palmoplantar keratoderma; pulmonic stenosis, hypertrophic cardiomyopathy, congenital heart defects, psychomotor delay, failure to thrive; RASopathy (BRAF, MAP2K1, MAP2K2, KRAS mutations) BJD 164:521–529, 2011   Differentiate from:   Capillary malformation/arteriovenous malformation syndrome – RASA1 mutation   Costello syndrome – pulmonic stenosis and hypertrophic cardiomyopathy; papillomas of nose and perianal regions; palmoplantar keratoderma, redundant skin of face; mild failure to thrive, developmental delay, outgoing personality; associated with rhabdomyosarcoma, neuroblastoma, transitional cell carcinoma

Alopecia in Neonates, Infants, and Toddlers   LEOPARD syndrome – pulmonic stenosis and hypertrophic cardiomyopathy; ocular hypertelorism, sensorineural hearing loss, short stature; lentigines, café au lait macules   Noonan’s syndrome – pulmonic stenosis and hypertrophic cardiomyopathy; congenital lymphedema, café au lait macules; low posterior hairline, webbed neck, pectus excavatum, short stature, bleeding tendency Cartilage hair hypoplasia – congenital hypotrichosis Ped Derm 28:494–501, 2011 Cockayne’s syndrome – sparse hair JAMA Derm 149:1414–1418, 2013 Collodion baby – eclabium; congenital erythroderma, ectropion, deformed ears, alopecia; mutation in ABCA12 BJD 166:218–221, 2012 Congenital alopecia areata JAAD 52:S8–11, 2005 Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis Ped Derm 29:756–758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985   Differential diagnosis:   Aplasia cutis congenita   Amniotic adhesions   Cutaneous trauma   Epidermolysis bullosa   Focal dermal hypoplasia   Intrauterine infection   Intrauterine or perinatal trauma Desmoplakin mutations – syndrome of dilated cardiomyopathy with severe left ventricular dysfunction, congenital alopecia, striate palmoplantar keratoderma, nail dystrophy, follicular hyperkeratosis with hyperpigmented plaques of elbows Ped Derm 32:102–108, 2015 Erythrokeratoderma-cardiomyopathy syndrome – recurrent infections, wiry or absent hair, dental enamel defects, nail dystrophy, sudden onset congestive heart failure; early death; dominant mutation in desmoplakin Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016 Halo scalp ring – associated with caput succedaneum; diffuse edema of scalp with serosanguinous extravasation above the periosteum Ped Derm 26:706–708, 2009 Hereditary fibrosing poikiloderma with tendon contracture, myopathy, fibrosis, and alopecia; FAM IIIB mutation – mimics RothmundThomson syndrome Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016   Poikiloderma of cheeks  Alopecia   Myopathy – fatty infiltration of muscles  Hypohidrosis   Lymphedema of hands and legs   Exocrine pancreatic insufficiency   Extraocular muscle weakness   Tendon contractures   Pulmonary fibrosis Hereditary hypotrichosis of scalp Ped Derm 19:148–150, 2002; Clin Genet 32:120–124, 1987 Hypohidrotic ectodermal dysplasia BJD 201–203, 2011 Hypotrichosis simplex BJD 201–203, 2011 Hutchinson-Gilford progeria syndrome – initial changes include alopecia, sclerodermoid changes of chest and abdomen, prominent

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superficial veins and dyspigmentation JAMA Derm 150:197–198, 2014 Hypotrichosis-Lymphedema-Telangiectasia-Renal failure syndrome – diffuse reticulated capillary malformation, hypertensive emergency with transient ischemic attack, dilatation or aortic root, pleural effusions, acute kidney injury, thin facies with telangiectasias of cheeks, livedo reticularis of trunk and extremities; mutation in SOX18 gene Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016 Ichthyosis prematurity syndrome (“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; erythrodermic infant with caseous vernix-like desquamation; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine scaling of scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin (thick vernix caseosa-like covering) (hyperkeratotic scalp) neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4 (FATP4) JAAD 66:606– 616, 2012; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008 Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, follicular occlusion triad, scalp cysts, nodules (trichilemmal tumors, squamous cell carcinoma), bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation JAAD 69:127–134, 2013; Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; JAAD 19:1124– 1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915 Loose anagen syndrome AD 133:1089–1093, 1997; AD 128:1349– 1353, 1992 Marie-Unna hypotrichosis Ped Derm 19:250–255, 2002 Meningeal heterotopia (ectopic rests of meningeal tissue that have lost central nervous system connection) and rudimentary or atretic meningoceles – exophytic nodular or cystic mass of occipital or parietal scalp – normal skin; glistening or bullous appearance, alopecia, hair collar Ped Derm 32:161–170, 2015 Netherton’s syndrome – short sparse hair Ped Derm 31:90–94, 2014 Neutral lipid storage disease (Chanarin-Dorfman disease) – autosomal recessive; focal or diffuse alopecia; congenital non-bullous ichthyosiform erythroderma, collodion baby; seborrheic dermatitislike rash of face and scalp; leukonychia; erythrokeratoderma variabilis-like presentation; mutation in ABHD5 which encodes protein of esterase/lipase/thioesterase subfamily BJD 153:838–841, 2005 Oculodentodigital dysplasia – autosomal dominant; hypotrichosis, curly hair, nail dystrophy, enamel hypoplasia Clinics in Dermatol 23:23–32, 2005 Omenn syndrome (familial reticulendotheliosis with eosinophilia) – neonatal exfoliative erythroderma, subacute combined immunodeficiency, diarrhea, hepatosplenomegaly, alopecia, failure to thrive, lymphadenopathy BJD 158:1153–1156, 2008; AD 136:875–880, 2000

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Severe combined immunodeficiency syndrome – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks); erythroderma, seborrheic dermatitis-like eruption; recurrent otitis media; mutations in cytokine common gamma chain (X-linked recessive), JAK3, RAG1 or RAG2, IL-7Rgamma, adenosine deaminase (autosomal recessive) AD 146:191–196, 2010; Ped Derm 26:213–214, 2009; AD 144:342–346, 2008; AD 136:875–880, 2000; J Pediatr 123:564–572, 1993

coloration; dermatomyositis with MDA-5 (CADM-40) (melanoma differentiation-associated gene 5) MDA 5 – RNA-specific helicase; all with interstitial lung disease; ulcers of nail folds, Gottron’s papules, and elbows; these patients demonstrate oral ulcers, hair loss, hand edema, arthritis/arthralgia, punched out ulcers of shoulder or metacarpophalangeal joints, digital necrosis, erythema of elbows and knees (Gottron’s sign), and tender gingiva JAAD 78:776–785, 2018; JAAD 65:25–34, 2011

Syphilis, congenital Ped Derm 23:564–566, 2006

Epidermolysis bullosa acquisita – scarring alopecia with erosions BJD 171:1022–1030, 2014; AD 131:618–95, 1995

Tinea capitis Ped Derm 28:188, 2011; J Eur Acad Dermatol Venereol 17:239–240, 2003; JAAD 42:1–20, 2000 Triangular alopecia Ped Derm 19:127–128, 2002; JAAD 31:205– 209, 1994 Vitamin D-resistant rickets Am J Med 77:805–811, 1984

ALOPECIA N = non-scarring S = scarring

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allogeneic hematopoietic cell transplant – amelanocytic anhidrotic alopecia areata-like phenotype after stem cell transplant AD 148:931–934, 2012 Alopecia areata – associations with adrenal disease, atopy, cytomegalovirus, Down’s syndrome, Hashimoto’s thyroiditis, pernicious anemia, vitiligo J Dermatol Sci 78:11–20, 2015; NEJM 366:1515–1525, 2012; JAAD 62:177–188, 2010; Cutis 82:104–110, 2008; acute diffuse and total alopecia JAAD 60:85–93, 2009; white overnight (Marie Antionette syndrome) AD 145:656, 2009; alopecia universalis JAMA Derm 150:1341–1344, 2014; perinevoid alopecia BJD 179:969–970, 2019 APECED (polyglandular autoimmune syndrome type 1) (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy) syndrome (autoimmune polyendocrine syndrome type 1) – autosomal recessive; mutation in AIRE gene (autoimmune regulator gene); chronic mucocutaneous candidiasis, hypoparathyroidism, Addison’s disease, diabetes mellitus type 1, thyroid autoimmune disease, gonadal failure, hepatitis, vitiligo, alopecia areata, pernicious anemia, intestinal malabsorption, keratinopathy, dystrophy of dental enamel and nails BJD 178:335–349, 2018; JAAD 73:255–264, 2015; JAAD 62:864–868, 2010 Atrichia with severe T-cell immunodeficiency and nail dystrophy Nature 398:473–474, 1999 Autosomal dominant ectodermal dysplasia with immunodeficiency BJD 178:335–349, 2018 Brunsting-Perry cicatricial pemphigoid (S) – scalp erosions, bullae, oral bullae and ulcers, scarring alopecia BJD 170:743–745, 2014 Chronic mucocutaneous candidiasis - crusted plaques, cicatricial alopecia, leukoplakia, dystrophic nails Ped Derm 34:609–611, 2017; NEJM 300:164–168, 1979; with dermatophytosis without endocrinopathy Cicatricial pemphigoid (S) AD 131:580–581, 1995; BJD 118:209– 217, 1988; Oral Surg 54:656–662, 1982 Dermatomyositis (NS or S) – diffuse hair loss; tender hyperkeratotic palmar papules in palmar creases of fingers with central white

Graft vs. host disease, chronic (S) – scarring and non-scarring alopecia JAAD 81:1134–1141, 2019; vitiligo and alopecia areata in chronic graft vs host disease JAMA Derm 151:23–332, 2015; JAAD 38:369–392, 1998 Immunodeficiency diseases (Wiskott-Aldrich syndrome, immunoglobulin deficiency diseases, severe combined immunodeficiency) – alopecia and dermatitis Ped Derm 16:95–102, 1999; combined immunodeficiency – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks) with progressive alopecia Rook p.498–499, 1998, Sixth Edition; common variable immunodeficiency – scarring alopecia with sarcoidal granulomas BJD 144:597–600, 2001; alopecia and infantile erythroderma highly suggestive of an immunodeficiency syndrome including Omenn syndrome AD 136:875–880, 2000 IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, pemphigoid nodularis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash; thyroid dysfunction, diabetes mellitus, hepatitis, nephritis, onychodystrophy, alopecia universalis; mutations in FOXP3 (forkhead box protein 3) gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia JAAD 73:355–364, 2015; BJD 160:645–651, 2009; ichthyosiform eruptions Blood 109:383–385, 2007; BJD 152:409–417, 2005; NEJM 344:1758– 1762, 2001; alopecia areata AD 140:466–472, 2004 Lupus erythematosus - systemic LE (NS or S) - diffuse, patchy, or anterior with broken hairs ("lupus hair") JAAD 81:1319–1329, 2019; Dermatol Clin 31:75–91, 2013; J Dermatol 34:451–455, 2007; Rook p. 2475, 1998, Sixth Edition; J Rheumatol 18:1185–1186, 1991; subacute cutaneous lupus erythematosus – non-scarring alopecia Med Clin North Am 73:1073–1090, 1989; JAAD 19:1957–1062, 1988; bullous LE, discoid LE (S), neonatal LE JAAD 50:25–32, 2004; Ped Derm 15:38–42, 1998; discoid LE (S) JAAD 75:1101– 1099, 2016; JAAD 71:415–428, 2014; BJD 160:482–501, 2009; BJD 159:1–22, 2008   Anagen effluvium   Discoid lupus erythematosus   Female pattern hair loss  Lupus hair – thin unruly hair along frontal hairline which easily fractures   Telogen effluvium   Non-scarring patch alopecia Morphea – including linear morphea (en coup de sabre) JAAD 75:1101–1099, 2016; pansclerotic morphea JAAD 53:S115–119, 2005; hypotrichosis Ped Derm 19:151–154, 2002 NEMO deficiency (X chromosomal ectodermal dysplasia with immunodeficiency) – brittle hair, hypotrichosis, alopecia BJD 178:335–349, 2018 Pemphigus erythematosus NEJM 369:2438–2449, 2013 Pemphigus foliaceus, juvenile – non-scarring alopecia BJD 161:472–474, 2009; fogo selvagem

Alopecia Pemphigus vulgaris Clin in Dermatol 37:618–628, 2019 Scleroderma (S) Clin in Dermatol 37:618–628, 2019 Severe combined immunodeficiency disorder JAAD 64:53–63, 2011 Sjogren’s syndrome – patchy alopecia; diffuse alopecia Winged helix deficiency (FOXN1 disease) BJD 178:335–349, 2018 X-linked agammaglobulinemia BJD 178:335–349, 2018

CONGENITAL Alopecia universalis congenita (congenital atrichia) – autosomal recessive; facial papules (atrichia with papular lesions); mutation in hairless (HR) gene BJD 158:834–835, 2008 Aplasia cutis congenita Atrichia congenitale (total alopecia) BJD 165:1127–1132, 2011 Congenital atrichia, palmoplantar keratoderma, mental retardation, early loss of teeth JAAD 30:893–898, 1994 Congenital atrichia, nail dystrophy, abnormal facies, retarded psychomotor development Ped Derm 5:236–242, 1988 Congenital atrichia – hairless gene 8q12 BJD 160:194–196, 2009 Congenital generalized hypotrichosis – short wiry hair; X-linked recessive Ped Derm 35:388–391, 2018; Ped Derm 28:133–134, 2011; Clin in Dermatol 23:47–55, 2005; JAAD 53:S130–134, 2005; BJD 143:612–617, 2000

Halo scalp ring – annular ring of alopecia; prolonged pressure on vertex by cervix Arch Pediatr Adolesc Med 156:188–190, 2002; AD 123:992–994, 1987; Ped Derm 2:52–54, 1984; associated with caput succedaneum; diffuse edema of scalp with serosanguinous extravasation above the periosteum Ped Derm 26:706–708, 2009; scarring AD 123:992–993, 1987 Heterotopic brain tissue – blue-red cystic mass with overlying alopecia JAAD 46:934–941, 2002 Meningothelial hamartoma (rudimentary meningocele) – alopecic fibrotic blue-purple plaque of scalp; may be tan-gray, red skin colored; nodular Ped Derm 28:677–680, 2011 Sequestrated meningocele (rudimentary meningocele) (type I cutaneous meningioma) AD 137:45–50, 2001; indented scarred patch of vertex of scalp JAAD 57:1101–1102, 2007 Unilateral localized failure of hair growth

DEGENERATIVE DISEASES Follicular degeneration syndrome in black patients (S) AD 130:763– 769, 1994; AD 128:68–74, 1992 Senescent balding Clin Dermatol 6:108–118, 1988

DRUGS

Congenital hypotrichosis simplex – autosomal dominant; corneodesmin 6p21.3 BJD 160:194–196, 2009; Ped Derm 16:301–304, 1999

Adalimumab AD 142:1654–1655, 2006

Congenital erosive dermatosis with reticulated supple scarring – most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails JAAD 45:946–948, 2001; AD 126:544–546, 1990; decrease in eyelashes Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; alopecia including eyelashes Ped Derm 26:735–738, 2009

Amitriptyline

Congenital hypotrichosis Congenital hypotrichosis with milia

Albendazole Allopurinol Amphetamine Anabolic steroids Anti-tumor necrosis factor agents – erythematous boggy crusted alopecic plaque of scalp Ped Derm 29:454–459, 2012 Beta blockers Bleomycin JAAD 40:367–398, 1999

Congenital ichthyosiform erythroderma

Bromocriptine Am J Pathol 162:1611–1621, 2003; Rook p. 3395, 1998, Sixth Edition

Congenital ichthyosis, alopecia, eclabion, ectropion, mental retardation – autosomal recessive Clin Genet 31:102–108, 1987

Busulfan – permanent alopecia BJD 152:1056–1058, 2005

Congenital ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis Am J Med Genet 13:186–189, 1998

Carbamazepine

Congenital triangular alopecia (temporal triangular alopecia) (may or may not be congenital) JAAD 75:634–637, 2016; JAAD 65:1071– 1072, 2011; Ped Derm 19:127–128, 2002; Cutis 69:255–256, 2002; JAAD 40:842–844, 1999; Ped Derm 12:301–303, 1995; JAAD 31:205–209, 1994; overlying frontotemporal suture or nape of neck JAAD 16:991–993, 1987; Cutis 28:196–197, 1981

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Captopril Chemotherapeutic agents – anagen and/or telogen effluvium JAAD 80:1179–1196, 2019; JAAD 40:367–398, 1999; permanent alopecia JAAD 63:333–336, 2010 Cholestyramine Cimetidine Int J Derm 22:202–203, 1983 Clofibrate

ECMO (extracorporeal membrane oxygenation) – erythema, edema, crusted ulcerations, scarring alopecia

Colchicine - anagen effluvium BJD 150:581–588, 2004; Hautarzt 31:161–163, 1980

Encephalocele

Coumarin JAAD 61:325–332, 2009

Hair collar sign JAAD 76:478–487, 2017  Cranial/bone defects with direct communication with the central nervous system   Venous malformations   Central nervous system abnormalities   Combined nevus   Meningeal heterotopia   Sinus pericranii  Paraganglioma

Dabrafenib – keratoacanthomas; plantar calluses, seborrheic keratosis, acneiform eruptions, epidermoid cysts, alopecia, verruca vulgaris BJD 167:1153–1160, 2012 Danazol – generalized alopecia Am J Obstet Gynecol 141:349–350, 1981 Dextran Dilantin Dixyrazine Acta DV (Stockh) 61:85–88, 1981

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Docetaxel/paclitaxel JAAD 71:203–214, 2014

Propranolol Cutis 24:63–65, 1979

Doxepin

Pyridostigmine

Pegylated liposomal doxorubicin – red hands and feet (acral erythrodysesthesia); follicular exanthema, intertrigo, alopecia, nail changes, stomatitis BJD 176:507–509, 2017

Quinacrine

Efalizumab AD 142:1653, 2006 Epidermal growth factor receptor inhibitors (chemotherapy) – curlier, finer more brittle hair Clin in Dermatol 29:587–601, 2011; JAAD 55:657–670, 2006 Erlotinib – scarring alopecia JAAD 64:998–999, 2011 Etanercept – lichen planopilaris (S) BJD 158:1161–1163, 2008 Etoposide/teniposide/amsacrine JAAD 71:203–214, 2014 5-fluorouracil, capecitabine, tegafur – alopecia JAAD 71:203–214, 2014

RAF inhibitors (MAPK pathway) – vemurafenib and dabrafenib – exanthema warts and other hyperkeratotic lesions, keratoacanthomas, squamous cell carcinoma, melanocytic nevi, keratosis pilaris, seborrheic dermatitis, hyperkeratotic hand-foot reactions, photosensitivity, panniculitis with arthralgias, alopecia JAAD 72:221–236, 2015 Retinoids – acitretin, isotretinoin BJD 122:751–756, 1990 Selective serotonin reuptake inhibitors – diffuse, non-scarring, generalized alopecia JAAD 56:848–853, 2007 Selenocystathionine (Leucena glauca) Nature 205:1185–1186, 1965 Sorafenib BJD 161:1045–1051, 2009; JAAD 60:299–305, 2009

Fluoxetine JAAD 71:415–428, 2014

Sunitinib BJD 161:1045–1051, 2009

Gefitinib (epidermal growth factor receptor inhibitor) – non-scarring inflammatory alopecia JAAD 55:349–353, 2006

Sulfasalazine

Gentamicin

Taxanes and adjuvant hormonal therapy – permanent alopecia JAAD 76:948–957, 2017

Gold

Testosterone

Griseofulvin – toxic epidermal necrolysis - personal observation

Thallium (manufacture of optical lenses) - anagen effluvium South Med J 59:436, 1966; JAMA 183:516–522, 1963

Haloperidol Hedgehog inhibitors BJD 173:262–264, 2015 Heparin JAAD 61:325–332, 2009; Heparinoids Hypocholesterolemic drugs Hydroxyurea JAAD 49:339–341, 2003 Ibuprofen

Thioureas Thyroid antagonists - thiouracil, carbimazole Acta Med Scand 124:266–281, 1946 Timolol Trametinib (MAP kinase inhibitor) (MEK inhibitor) – angular cheilitis, xerosis, bacterial folliculitis, acneiform eruptions, paronychia, thinning hair Ped Derm 34:90–94, 2017

Indinavir – retinoid-like side effects JAAD 63:549–561, 2010; JAAD 46:284–293, 2002

Trimethadione

Indomethacin

Tumor necrosis factor alpha antagonists – alopecia areata J Drugs in Dermatol 12:713–714, 2013

Infliximab AD 142:1653, 2006 Iodine-induced hypothyroidism BJD 79:103–105, 1967 Ipilimumab JAAD 71:161–169, 2014 Levodopa Br Med J ii:47, 1971 Lithium JAAD 71:415–428, 2014 Methotrexate/antimetabolites Metoprolol JAAD 71:415–428, 2014 Nicotinic acid Nilotinib (multiple tyrosine kinase inhibitor) – inflammatory nonscarring alopecia JAMA Derm 149:330–332, 2013 Nitrofurantoin

Triparanol AD 87:372–377, 1963

Valproic acid JAAD 71:415–428, 2014; Rook p. 3395, 1998, Sixth Edition Vismodegib (hedgehog pathway inhibitor) – alopecia, dysgeusia, muscle spasms BJD 172:1671–1672, 2015; JAAD 72:221–236, 2015; JAAD 71:217–227, 2014

EXOGENOUS AGENTS Bismuth - anagen effluvium Colchicum (tubers of Gloriosa superba, Lecythis ollaria, Leucaena leucocephala, cucurbit) JAMA Derm 254:617–618, 2018

Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-­like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015

Drug overdose

Non-steroidal anti-inflammatory drugs

Lead - anagen effluvium

Octreotide BJD 149:655–656, 2003

Mimosine – amino acid of legumes

Oral contraceptives

Niacin

PDL-1 inhibitors – alopecia areata BJD 176:1649–1652, 2017 Potassium thiocyanate

Synthetic opioid MT-45 – hair depigmentation, hair loss, Mees’ lines BJD 176:1021–1027, 2017

Pramipexole (dopamine agonist) JAAD 55:S103–104, 2006

Vincristine/vinblastine/vinorelbine JAAD 71:203–214, 2014

Probenecid

Vitamin A intoxication Arch Intern Med 112:462–466, 1963

Hair cosmetics Acute hair relaxer BJD 156:1394–1397, 2007 Hairpin-induced scarring alopecia Cutis 85:242–245, 2010 Hypervitaminosis A - personal observation Irritant contact dermatitis

Alopecia

INFECTIONS AND INFESTATIONS AIDS Cutis 76:361–366, 2005; JAAD 34:63–68, 1996 Ant infestation (Pheidole) – hair breakage Cutis 96:221–222, 2015; Ped Derm 23:519–520, 2006 Bacterial infections, sycosis Candida infection

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JAAD 60:169–171, 2009; J Cutan Pathol 34:721–725, 2007; AD 142:1643–1648, 2006; JAAD 52:540–541, 2005; Am J Surg Pathol 29:241–246, 2005; JAAD 52:540, 2005; JAAD 50:318–322, 2004; JAAD 50:310–315, 2004; JAAD 43:118–122, 2000; J Invest Dermatol Symp Proc 4:268–271, 1999; Hautarzt 46:841–846, 1995 Tufted folliculitis (S) BJD 160:482–501, 2009; JAAD 21:1096–1099, 1989

Carbuncle (S) Demodicidosis – mimicking favus; hyperkeratotic patchy alopecia, papules, vesicles, pustules JAAD 57:S19–21, 2007

INFILTRATIVE DISEASES

Favus (S)

Amyloidosis – patchy or diffuse alopecia – scarring and non-scarring Dermatol Online J 19:11, 2013; JAAD 46:434–436, 2002; AD 127:1067–1068, 1991; Medicine 54:271–299, 1975; alopecia universalis AD 117:818–826, 1981; secondary systemic (AA amyloidosis) – occasional purpura, easy bruisability, alopecia BJD 152:250–257, 2005

Folliculitis (NS) Furuncles (NS and S) Herpes zoster (S) Kerion (NS and S) Clin Dermatol 18:735–743, 2000 Leishmaniasis (S)- Old World leishmaniasis – brown plaque of scalp with alopecia AD 147:1097–1102, 2011 Leprosy - borderline tuberculoid, tuberculoid – well-defined edge, red, copper or purple colored plaque with hypopigmented center; hairless hypopigmented macule with dry, hairless anesthetic surface with fine wrinkling JAMA Derm 153:313–314, 2017; Int J Lepr Other Mycobact Dis 67:388–391, 1999; lepromatous with leonine facies; Lucio’s phenomenon – gradual loss of eyebrow, eyelash, and body hair with generalized sclerodermoid thickening of skin Lyme disease JAAD 49:363–392, 2003 Merkel cell polyoma virus – widespread follicular papules; alopecia BJD 175:1410, 2016 Mycobacterium neoaurum – scarring alopecia BJD 157:204–206, 2007 Mycobacterium tuberculosis (S)- lupus vulgaris Myiasis Pheidole ants – non-scarring alopecia due to hair nibbling AD 144:1526–1527, 2008 Scabies - crusted Cutis 61:87–88, 1998 Syphilitic alopecia - patchy (symptomatic alopecia) or diffuse (essential syphilitic alopecia) Cutis 76:361–366, 2005; JAAD 32:840–844, 1995; tertiary syphilis (S) Tick bite – alopecia at site of tick attachment to scalp Cutis 98:88–90, 2016; JAAD 49:363–392, 2003; Clin Exp Dermatol 7:537–542, 1982; pigeon tick (Argus reflexus) Dermatologica 135:60–65, 1967; moth-eaten alopecia JAAD 49:363–392, 2003 Tick-borne lymphadenopathy (Rickettsia slovaca, R . rioja, R. raoultii); Dermacentor marginatus – scalp eschar with facial edema; residual alopecia JAAD 75:1–16, 2016 Tinea barbae Tinea capitis (S or NS) – mimicking scarring alopecia JAAD 60:490–495, 2009; in infants BJD 151:886–890, 2004; favus (S) yellowish cup-shaped crusts (scutula) JAAD 53:931–951, 2006; Dermatologica 125:369–381, 1962; in elderly BJD 144:898–900, 2001; tinea incognito; tinea capitis mimicking dissecting cellulitis – alopecia and inflammatory nodules of scalp Ped Derm 30:753–754, 2013 Trichodysplasia of immunosuppression (trichodysplasia spinulosa, DNA polyoma viral-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy) - transplant patient; particulate matter, progressive alopecia of eyebrows initially, then scalp and body hair and red follicular papules of nose, ears, forehead; thickened skin, eyebrow alopecia, leonine facies JAAD 75:1–16, 2016; AD 148:726–733, 2012; AD 146:871–874, 2010;

Langerhans cell histiocytosis Follicular mucinosis (alopecia mucinosa) (S) JAAD 75:1099–1101, 2016; including scalp alopecia JAAD 75:1101–1099, 2016; ; BJD 163:420–423, 2010; BJD 160:482–501, 2009; BJD 159:1–22, 2008; AD 136:235–242, 2000; JAAD 38:622–624, 1998; Dermatology 197:178–180, 1998; JAAD 10:760–768, 1984; AD 76:419–426, 1957; alopecic scaly plaque of face (follicular mucinosis in childhood) Ped Derm 30:192–198, 2013 Lichen myxedematosis (scleromyxedema, papular mucinosis) Mastocytosis (S) (urticaria pigmentosa) Cutis 58:329–336, 1996

INFLAMMATORY DISEASES Acne keloidalis nuchae (S) BJD 160:482–501, 2009; BJD 159:1–22, 2008; Clin Dermatol 19:211–225, 2001; Dermatol Clin 6:387–395, 1988 Blepharitis – loss of eyelashes Chronic illness Dissecting cellulitis of the scalp (perifolliculitis capitis abscedens et suffodiens) (Hoffman’s disease) (S) – painful, sterile abscesses with interconnecting sinus tracts; scarring; keloids JAAD 75:1101–1099, 2016; BJD 174:916–918, 2016; JAAD 71:415–428, 2014; JAAD 62:534–536, 2010; BJD 160:482–501, 2009; BJD 159:1–22, 2008; BJD 152:777–779, 2005; AD 136:235–242, 2000; Dermatol Clin 6:387–395, 1988; Cutis 32:378–380, 1983; Minn Med 34:319–325, 1951; AD 23:503–518, 1931 Folliculitis decalvans (S) – progressive purulent folliculitis; painful pustules; boggy indurated scarring JAAD 79:878–883, 2018; JAAD 75:1099–1101, 2016; JAAD 72:1085–1087, 2015; JAAD 71:415– 428, 2014; BJD 160:482–501, 2009; BJD 159:1–22, 2008; Cutis 78:162–164, 2006; Clin Dermatol 18:735–743, 2000; AD 136:235– 242, 2000 Folliculitis spinulosa decalvans – pustules, keratotic papules of scalp, scarring alopecia Cutis 98:175–178, 2016; Ped Derm 23:255–258, 2006 Keratosis follicularis spinulosa decalvans (S) – widespread keratosis pilaris and scarring alopecia; scalp pustules, photophobia, corneal dystrophy, focal palmoplantar keratoderma, and atopy JAAD 75:1101–1099, 2016; Ped Derm 30:674–682, 2013; BJD 160:482– 501, 2009; BJD 159:1–22, 2008 Kikuchi-Fujimoto disease – young Asians; fever, lymphadenopathy, respiratory symptoms, arthralgias and myalgias; ulcers, red plaques, and papules, facial erythema, red macules and patches; scattered indurated nodules, photoeruptions; leukocytoclastic vasculitis; pruritus, conjunctival injection, oral ulcers NEJM 369:2333–2343,

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2013; Int J Dermatol 51:564–567, 2012; Indian J Otolaryngol Head Neck Surg 63:Suppl 1:110–112, 2011; Arch Pathol Lab Med 134:289–293, 2010; Clin Rheumatol 26:50–54, 2007; BJD 144:885– 889, 2001 Pyoderma gangrenosum (S) Sarcoidosis (S) - red plaques of scalp with scarring alopecia JAAD 75:1101–1099, 2016; Dermatol Clin 33:509–630, 2015; JAAD 59:143–145, 2008; AD 138:259–264, 2002; JAAD 44:725–743, 2001; AD 133:882–888, 1997; extensive depigmented scars on scalp JAAD 59:S126–127, 2008; alopecia of shin BJD 109 (Suppl.24):66–67, 1983; ulcerative sarcoid of scalp with alopecia JAMA Derm 155:238, 2019; cicatricial alopecia AD 107:758, 1973

METABOLIC DISEASES Acrodermatitis enteropathica (NS) - periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche; mutation in SLC39A4 encodes ZIP4 zinc transporter BJD 161:184– 186, 2009; JAAD 56:116–124, 2008;Ped Derm 19:426–431, 2002; Acta DV (Stockh) 59:177–178, 1979; with anorexia nervosa JAMA 288:2655–2656, 2002 Acromegaly Addison’s disease – decreased axillary and pubic hair in females JAAD 58:522–524, 2008 Androgenetic alopecia Argininosuccinic aminoaciduria – argininosuccinate lyase deficiency; impaired nitrogen metabolism; multiorgan toxicity seizures, hyperammonemic coma, growth retardation; trichorrhexis nodosa, fractured hair, and other hair shaft abnormalities BJD 161:1379– 1383, 2009; JAAD 59:1–22, 2008; Ped Derm 24:25–27, 2007; Clin in Dermatol 23:47–55, 2005; JID 48:260, 1967 Biotin deficiency (multiple carboxylase deficiencies) – psoriasiform, periorificial intertriginous dermatitis; diarrhea, alopecia Ped Derm 33:457–458, 2016; NEJM 304:820–823, 1981 Biotin-responsive multiple carboxylase deficiency – alopecia, developmental delay, hypotonia, seizures, biotinidase deficiency Am J Med Genet 66:378–398, 1996; diffuse alopecia Adv Pediatr 38:1–21, 1991; AD 123:1696–1698, 1987 Biotinidase deficiency – trichorrhexis nodosa with broken hairs JAMA Derm 149:357–362, 2013; Clin in Dermatol 23:47–55, 2005 Citrullinemia – deficiency of argininosuccinic acid synthetase; trichorrhexis nodosa and other hair shaft abnormalities JAAD 59:1–22, 2008; JAAD 12:203–206, 1986; Arch Dis Child 49:579– 581, 1974 Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 167:988–900, 2012 Cretinism – coarse facial features, lethargy, macroglossia, cold dry skin, livedo, umbilical hernia, poor muscle tone, coarse scalp hair, synophrys, no pubic or axillary hair at puberty Rook p. 2708, 1998, Sixth Edition

Defect in incorporation of histidine, tyrosine, and arginine into hair keratin Pediatrics 37:498–502, 1966 Essential fatty acid deficiency - telogen effluvium; severe xerosis with underlying erythema, hair loss with hypopigmentation, and weeping intertriginous rash Ped Derm 16:95–102, 1999 Estrogen excess Hair loss metabolic workup   Serum ammonia   Urine organic acids   Plasma amino acids   Urine ketones   Blood gases   Basic metabolic panel  Carnitine  Acylcarnitine  Biotinidase Hartnup disease – autosomal recessive; defective transport of tryptophan in small intestine and kidneys; pellagra-­like photosensitive eruption; cerebellar ataxia; psoriasiform red scaly plaques, generalized alopecia, widespread edema Ped Derm 23:262–265, 2006 Hemochromatosis – especially axillary and pubic hair J Drugs in Dermatol 9:719–722, 2010; Cleve Clin J Med 76:599–606, 2009; AD 113:161–165, 1977; Medicine 34:381–430, 1955 Hereditary Vitamin D-resistant rickets – autosomal recessive; normal hair at birth; alopecia, growth failure, developmental delay Ped Derma 31:519–520, 2014 Holocarboxylase deficiency AD 123:1696–1698, 1987; Pediatrics 68:113–118, 1981 Homocystinuria – cystathionine-beta synthase deficiency; fine sparse, brittle hair, marfanoid habitus, malar rash, larger facial pores, livedo reticularis, tissue paper scars, superficial thrombophlebitis JAAD 46:161–183, 2002; JAAD 40:279–281, 1999; JAAD 40:279–281, 1999 Hyperandrogenism  Postmenopausal hyperandrogenism (hirsutism and alopecia) NEJM 373 1660–1666 , 2015   Functional hyperandrogenism     Polycystic ovarian syndrome     Congenital adrenal hyperplasia     Ovarian hyperthecosis     Cushing’s syndrome     Acromegaly     Exposure to testosterone or dehydroepiandrosterone dione sulfate    Tumor-related hyperandrogenism     Androgen-secreting adrenal adenomas and carcinomas     Androgen-secreting ovarian tumors     Metastatic neuroendocrine tumors Hyperlysinemia - fine sparse hypopigmented hair Hyperthyroidism JAAD 26:885–902, 1992 Hypocalcemia AD 121:646–647, 1985 Hypoparathyroidism, idiopathic - non-scarring JAAD 15:353–356, 1986 Hypopituitarism – loss of axillary and pubic hair; Sheehan’s syndrome – skin is yellow, dry

Cushing’s disease due to recurrent pituitary tumor - personal observation

Hypothyroidism (myxedema) – coarse, sparse scalp hair, loss of pubic, axillary, facial hair NEJM 372:764, 2015; JAAD 26:885–902, 1992; AD 106:349–352, 1972

Cushing’s syndrome – acne and hirsutism; male pattern alopecia; Semin Dermatol 3:287–294, 1984

Iron deficiency BJD 84:83–85, 1971; Acta DV (Stockh) 43:652–659, 1963

Alopecia Isovaleric acidemia Kwashiorkor - protein and caloric deprivation – dry, brittle, lusterless prematurely gray hair which becomes sparse JAMA Derm 150:910– 911, 2014; JAMA Derm 150:85–86, 2014; JAAD 21:1–30, 1989; telogen effluvium AD 137:630–636, 2001; Cutis 67:321–327, 2001 Leydig cell rumor - personal observation Liver disease, chronic – body and pubic hair thinned Rook p. 2725, 1998, Sixth Edition; cirrhosis – zinc deficiency; generalized dermatitis of erythema craquele (crackled and reticulated dermatitis) with perianal and perigenital erosions and crusts; cheilitis, hair loss Ann DV 114:39–53, 1987 Malabsorption Malnutrition Seminars in Dermatol Vol 4:53–64, 1985 Marasmus (NS) JAAD 21:1–30, 1990 Meralgia paresthetica Methylmalonic acidemia - deficiency of methylmalonyl coenzyme A mutase or its cofactors adenosylcobalamin (vitamin B12) and methylcobalamin; affects metabolism of four amino acids (valine isoleucine, threonine, methionine); these patients fed low protein diets limited in branched chain amino acids Ped Derm 24:455–456, 2007; Dermatol Pediatr Lat 1:46–48, 2003; Ped Derm 16:95–102, 1999; AD 133:1563–1566, 1997; J Pediatr 124:416–420, 1994; BJD 131:93–98, 1994 Mitochondrial disorders – alopecia with or without hair shaft abnormalities including trichothiodystrophy, trichoschisis, tiger tail pattern, pili torti, longitudinal grooving, and trichorrhexis nodosa Pediatrics 103:428–433, 1999

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Pseudoglucagonoma syndrome due to malnutrition AD 141:914– 916, 2005 Renal disease, chronic – uremia; sparse body hair Ghatan, Second Edition, 2002, p.177 Scurvy Ped Derm 25:644–646, 2008; JAAD 41:895–906, 1999 Selenium deficiency - xerosis, alopecia, leukotrichia, leukonychia; pancytopenia, muscle weakness, muscle pain, cardiac arrhythmia, unsteady gait, distal paresthesias JAAD 80:1215–1231, 2019; Nutrition 23:782–787, 2007; Nutrition 12:40–43, 1996 Telogen effluvium AD 83:175–198, 1961; postpartum telogen effluvium J Drugs Dermatol 14:512–513, 2015 Vitamin B12 deficiency – sparse thin scalp hairs, generalized hyperpigmentation, hyperpigmentation over dorsal hands and feet, reticulate hyperpigmentation, glossitis, cheilitis Ped Derm 35:796– 799, 2018 Vitamin D deficiency Cutis 102:53–55, 2018 Vitamin D-dependent resistant rickets type IIA – autosomal recessive; hair present at birth then lost in first 12 months; mutation in hairless (HR) gene AD 141:343–351, 2005; Clin in Dermatol 23:47–55, 2005; AD 139:1591–1596, 2003; JID 117:612–617, 2001; Am J Med 77:805–811, 1984; congenital rickets Clin Dermatol 18:735–743, 2000; clinically and histologically similar to atrichia with papular lesions Zinc deficiency, acquired JAAD 69:616–624, 2013; cystic fibrosis personal observation

Myotonic dystrophy – frontal balding JAAD 50:S1–3, 2004

NEOPLASTIC DISEASES

Multiple carboxylase deficiency – total scalp and universal alopecia Ped Derm 21:231–235, 2004; Ped Derm 16:95–102, 1999

Adenoid cystic carcinoma – skin colored scalp nodule with alopecia Cutis 81:243–246, 2008

Necrobiosis lipoidica diabeticorum (S) Dermatologica 135:11–26, 1967

Angiosarcoma JAAD 38:837–840, 1998; (S)AD 116:683–686, 1980

Orotic aciduria Br Med J i:546–552, 1965

Aplastic nevus – complete absence of skin appendages Cutis 12:386–389, 1973

Osteoma cutis – scarring alopecia BJD 146:1075–1080, 2002

Basal cell carcinoma (S)

Ovarian arrhenoblastoma - personal observation

Basal cell nevus (linear basal cell nevus) – resemble comedones; usually linear translucent telangiectatic papules, may ulcerate; macular hypopigmentation, alopecia, cysts, striae Cutis 46:493– 494, 1990; BJD 74:20–23, 1962

Phenylketonuria – fine sparse hypopigmented hair (alopecia with hair breakage); trichorrhexis nodosa Ped Derm 30:674–682, 2013; Phrynoderma (hypovitaminosis A) Polycystic ovarian disease – acanthosis nigricans, acne vulgaris, hirsutism, hair loss JAAD 71:847–856, 2014; NEJM 352:1223– 1236, 2005; Clin Endocrinol 30:459–464, 1989; Am J Obstet Gynecol 29:181–191, 1935   Differential diagnosis:   Cushing’s syndrome   Hyperprolactinemia   Hypothyroidism   Late onset congenital adrenal hyperplasia – increased 17 hydroxy-progesterone   Pregnancy   Premature ovarian failure – increased FSH, increased LH, decreased or normal estradiol   Virilizing ovarian or adrenal tumor – total testosterone >200ng/ dl; DHEAS >700 ug/dl; increased androstenedione Porphyria – congenital erythropoietic porphyria (S) Rook p. 2595, 1998, Sixth Edition; porphyria cutanea tarda, variegate porphyria, hepatoerythropoietic porphyria; pseudosclerodermatous PCT Cutis 76:329–333, 2005; Clin Liver Dis 5:979–1008, 2001

Basaloid follicular hamartoma – solitary plaque of alopecia BJD 146:1068–1070, 2002 Benign cephalic histiocytosis Blue nevus - giant alopecic nodule (cellular blue nevus) BJD 126:375–377, 1992 Cellular blue nevi Ped Derm 14:199–203, 1997 Cerebriform intradermal nevus Ped Derm 24:141–143, 2007; J Eur Acad DV 16:529–531, 2002 Cylindroma Dermatofibrosarcoma protuberans, congenital – annular red plaque, pink alopecic plaque, red macule, blue plaque, hypopigmented plaque AD 143:203–210, 2007 Eccrine sweat gland hamartoma AD 99:478–493, 1969 Epidermal nevus (NS and S) Rook p. 2912, 1998, Sixth Edition Epidermoid cyst - personal observation Generalized follicular harmatoma (S) AD 131:454–8, 1995; AD 107:435–440, 1973; AD 99:478–493, 1969 Hair follicle hamartoma BJD 143:1103–1105, 2000; follicular hamartoma of the face with myasthenia gravis Clin Exp Derm 6:283–289, 1981; JAAD 39:853–857, 1998

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Leukemia - T-cell prolymphocytic leukemia – facial purpuric plaques; petechial periorbital eruption JAAD 55:467–477, 2006; HTLV-1 leukemia/lymphoma - personal observation Lymphomas, including CTCL (S) JAAD 70:205–220, 2014; JAAD 47:914–918, 2002; Hodgkin’s disease – due to rubbing, ichthyosiform changes, endocrine dysfunction, cellular infiltration folliculotropic (pilotropic) CTCL –JAAD 48:448–452, 2003; alopecia with nodules AD 146:607–613, 2010; annular red plaque of scalp with scarring alopecia – primary cutaneous follicle center B-cell lymphoma BJD 165:204–208, 2011; syringotropic CTCL – hypopigmented alopecic plaque with follicular papules JAAD 61:133–138, 2009; JAAD 60:152–154, 2009; subcutaneous panniculitis-like T-cell lymphoma mimicking alopecia areata BJD 147:785–788, 2002; scarring alopecia of scalp; large milia with facial alopecia - cerebriform lesions of scalp - folliculotropic cutaneous T-cell lymphoma AD 144:738–746, 2008; alopecia areata-like in CTCL JAAD 64:53–63, 2011; patchy alopecia at sites of CTCL cutaneous B-cell lymphoblastic lymphoma JAAD 66:51–57, 2012; Sezary syndrome NEJM 369:559–569, 2013; Woringer-Kolopp disease – personal observation; primary cutaneous B-cell lymphoma – acute alopecia with pruritic erythema of scalp JAAD 73:893–894, 2015 Melanocytic nevus Meningioma, congenital - nodule with overlying alopecia or hypertrichosis JAAD 46:934–941, 2002; Eur J Pediatr Surg 10:387–389, 2000; primary cutaneous meningioma – overlying alopecia Cancer 34:728–744, 1974 Metastatic tumors (S) (alopecia neoplastica) – breast, lung, kidney the most common JAAD 63:545–547, 2010; JAAD 62:536–538, 2010; Cancer 19:162–168, 1966 Multicentric reticulohistiocytosis JAAD 10:296–297, 1984 Myeloma Nerve sheath myxoma JAAD 16:209–211, 1987 Nevus psiloliparus – well-demarcated, smooth alopecic plaque of scalp; mesodermal nevus with paucity of hair and excess fat tissue; appears in encephalocranial lipomatosis Ped Derm 31:746–748, 2014; Ped Derm 22:206–209, 2005 Nevus sebaceus with or without malignancy (S) Ped Derm 26:236–237, 2009; BJD 82:99–117, 1970 Papular xanthoma Porokeratosis of Mibelli (S) Porokeratotic eccrine ostial and dermal duct nevus, generalized blaschko-distributed verrucous plaques; non-scarring alopecia, hypohidrosis, teeth in disarray, deafness JAAD 59:S43–45, 2008 Primary cutaneous adenoid cystic carcinoma Rare Tumors 3 (1):e3. doi,10.408/rt2011e3 Proliferating trichilemmal cysts and cicatricial alopecia AD 107:435– 438, 1973 Seborrheic keratosis Squamous cell carcinoma (S) Syringocystadenoma papilliferum AD 71:361–372, 1955 Syringomas JAAD 13:528–529, 1985 (NS); AD 116:843–844, 1980 (S) Woolly hair nevus Ped Derm 27:100–101, 2010

PARANEOPLASTIC DISORDERS Brain tumors of mid-brain and brainstem Arch Dermatol Syphilol 176:196–199, 1937 Necrobiotic xanthogranuloma with paraproteinemia

Glucagonoma syndrome – periorbital and perioral erythema; alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; skin rash, angular stomatitis, cheilosis, beefy red glossitis, blepharitis, conjunctivitis, alopecia, crumbling nails; rarely, associated with MEN I or IIA syndromes BJD 174:1092–1095, 2016; JAMA Derm 345–347, 2016; JAAD 54:745–762, 2006; JAAD 12:1032–1039, 1985; Int J Derm 43:12–18, 2004; AD 133:909, 912, 1997; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979; AD 45:1069–1080, 1942

PHOTODERMATOSES Chronic actinic dermatitis – acute, subacute, or chronic dermatitis with lichenification, papules, plaques, erythroderma, stubby scalp and eyebrow hair AD 136:1215–1220, 2000; AD 130:1284–1289, 1994; JAAD 28:240–249, 1993; AD 126:317–323, 1990; sensitization by sesquiterpene lactone mix BJD 132:543–547, 1995; associated with musk ambrette Cutis 54:167–170, 1994; JAAD 3:384–393, 1980 Polymorphic light eruption - suboccipital actinic alopecia and actinic madurosis Int J Dermatol 30:375–376, 1991

PRIMARY CUTANEOUS DISEASES Acne keloidalis JAAD 75:1101–1099, 2016 Acne necrotica (S) JAAD 75:1101–1099, 2016 Acne necrotica varioliformis (necrotizing lymphocytic folliculitis) – edematous lesions with central umbilication; then scalp papulopustules with central necrosis and scarring BJD 160:482–501, 2009; BJD 159:1–22, 2008 Adolescent onset ichthyosiform erythroderma BJD 144:1063–1066, 2001 Alopecia and follicular papules Int J Derm 38 (Suppl 1):31, 1999   Alopecia, keratosis pilaris, cataracts and psoriasis  Alopecia mucinosa (follicular mucinosis) Dermatology 197:178– 180, 1998; AD 125:287–292, 1989; JAAD 10:760–768, 1984; AD 76:419–426, 1957  Cardiofaciocutaneous syndrome – sporadic, congenital atrichia, follicular keratotic papules, dermatitis, chylosis, keratosis pilaris atrophicans, seborrheic dermatitis, café au lait macules, nevi, hemangiomas, hyperpigmentation Ped Derm 20:48–51, 2003   Down’s syndrome   Hayden’s disease  Hereditary mucoepithelial dyskeratosis – autosomal dominant; keratitis, non-scarring alopecia, keratosis pilaris, erythema of oral and nasal mucous membranes, cervix, vagina, and urethra; increased risk of infections, fibrocystic lung disease JAAD 21:351–357, 1989  Ichthyosis follicularis with atrichia and photophobia (IFAP) – collodion membrane and erythema at birth; generalized follicular keratoses, non-scarring alopecia, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis JAAD 46:S156–158, 2002; Am J Med Genet 85:365–368, 1999   AD 125:103–106, 1989; Dermatologica 177:341–347, 1988  Monilethrix   Noonan’s syndrome   Pachyonychia congenita   Schopf-Schulz-Passarge syndrome Alopecia and neuropsychiatric manifestations Ped Derm 20:48–51, 2003   Dubowitz syndrome   Hereditary ectodermal dysplasia   Menkes’ kinky hair syndrome

Alopecia   Moynihan syndrome   Nicolaides-Baraitser syndrome   Periniolas syndrome   Shapiro syndrome   Shokeir syndrome   Steijlen syndrome  Trichothiodystrophy Alopecia areata JAMA Derm 150:748–751, 2014; JAMA Derm 149:877–879, 2013 Alopecia parvimacularis (S) – irregular angular areas of scarring and non-scarring alopecia Dermatol Wochenschr 149:381–388, 1964 Alopecia with twisted hair AD 148:143, 2012   Anhidrotic ectodermal dysplasia   Bazex syndrome   Bjornstad syndrome   Crandall’s syndrome  Holocarboxylase deficiency (biotin-responsive multiple carboxylase deficiency)   Menkes’ kinky hair syndrome   Pili torti   Pollitt syndrome  Pseudomonilethrix Amicrobial pustulosis – exudative erythema, erosions, pustules, diffuse alopecia with dermatitis; associated with systemic autoimmune disorders; scalp, axillae, ears, thighs JAAD 57:523–526, 2007; BJD 154:568–569, 2006; Communication no.11. Journees Dermatologiques de Paris, March 1991. Anagen effluvium Clin Dermatol 18:735–743, 2000 Androgenetic alopecia JAAD 18:1073–1078, 1988 Anterolateral leg alopecia Cutis 70: 215–216, 200 Atopic dermatitis JAAD 64:53–63, 2011 Atrichia with papular lesions BJD 158:834–835, 2008; AD 141:343– 351, 2005 Atrophoderma vermiculata – honeycomb atrophy of cheeks with scarring alopecia of scalp AD 75:283–289, 1957 Autosomal recessive ectodermal dysplasia – alopecia, hypodontia BJD 179:758–760, 2018 Autosomal recessive hypotrichosis simplex – mutations in desmoglein 4, phospholipase H (LIPH), and 6 protein coupled receptor (P2RY5); 13q14.11-q21.33; sparse to absent scalp hair, eyebrows, and eyelashes, axillary, and body hair; normal beard BJD 160:1006–1010, 2009; BJD 160:194–196, 2009 Autosomal recessive hypotrichosis simplex – phospholipase H (LIPH); sparse scalp hair and sparse eyebrows BJD 160:194–196, 2009 Bubble hair – increased hair fragility JAAD 71:415–428, 2014 Central centrifugal cicatricial alopecia (follicular degeneration syndrome) - papules of scalp Ped Derm 34:133–137, 2017; JAAD 75:1101–1099, 2016; JAAD 71:415–428, 2014; AD 147:909–914, 2011; JAAD 64:245–252, 2011; JAAD 60:660–668, 2009; JAAD 60:574–578, 2009; BJD 160:482–501, 2009; BJD 159:1–22, 2008; BJD 157:981–988, 2007; JAAD 53:1–37, 2005; AD 136:235–242, 2000 Cicatricial marginal alopecia BJD 161:213–215, 2009; BJD 160:62–68, 2009 Cutis laxa – generalized cutis laxa – autosomal dominant – lesions often preceded in infancy by episodes of edema; infantile genitalia; scant body hair Rook p. 2019–2020, 1998, Sixth Edition Darier’s disease (S) Eosinophilic cellulitis (S)

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Eosinophilic pustular folliculitis of Ofuji – scarring alopecia Dermatologica 157:193–205, 1974 Epidermolysis bullosa – epidermolysis bullosa simplex with alopecia Ped Derm 36:430–436, 2019; EBS – lethal acantholytic; EBS, plakophilin deficiency, JEB, Herlitz type, JEB, non-Herlitz type generalized; DDEB, generalized; RDEB severe generalized, RDEBm generalized other JAAD 58:931–950, 2008; Clin in Dermatol 23:47–55, 2005; non-Herlitz junctional EB JAAD 46:510– 516, 2002; generalized atrophic benign EB (GABEB) (mitis) – nonlethal junctional – generalized blistering beginning in infancy; atrophic scarring; alopecia of scalp, partial alopecia of eyebrows, eyelashes JAAD 46:510–516, 2002; AD 145:150, 1996; Dermatologica 152:72–86, 1976; cicatricial junctional EB – scarring, alopecia, syndactyly, contractures JAAD 12:836–844, 1985; dominant or recessive dystrophic (S) BJD 146:267–274, 2002; Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 135–151; epidermolysis bullosa simplex with anodontia/hypodontia (Kallin syndrome) – thickened or curved nails, alopecia with brittle hair, bullae of hands and feet, nail dystrophy, anodontia, alopecia, deafness Acta DV 65:526–531, 1985 Epidermolysis bullosa simplex with ectodermal dysplasia and skin fragility – autosomal recessive; plakophilin 1 mutation; palmoplantar keratoderma, woolly hair and alopecia, anhidrosis until first year Epidermolysis bullosa, autosomal recessive – blisters and erosions, mild skin fragility, fatal interstitial lung disease, nephrotic syndrome, sparse fine hair, large dystrophic toenails with distal onycholysis; integrin alpha-B mutation NEJM 366:1508–1514, 2012 Epidermolysis bullosa - ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013 Epidermolytic hyperkeratosis – patchy scarring alopecia Rook p.1506, 1998, Sixth Edition Erosive pustular dermatosis of the scalp – in elderly; erosions, sterile pustules, scarring alopecia; sign of chronic actinic damage JAAD 76:1109–1114, 2017; JAAD 75:1101–1099, 2016; AD 147:1368–1370, 2011; AD 147:252–253, 2011; AD 145:1340–1341, 2009; JAAD 60:521–522, 2009; AD 144:795–800, 2008; Ped Derm 23:533–536, 2006; AD 139:712–714, 2003; Dermatol Surg 27:766–767, 2001; JAAD 28:96–98, 1993; Hautarzt 43:576–579, 1992; BJD 118:441–444, 1988 (S); BJD 100:559–566, 1979; chronic atrophic erosive dermatosis of the scalp and extremities JAAD 57:421–427, 2007 Exfoliative dermatitis (NS) Facial hemiatrophy (Romberg’s syndrome) (S) Familial focal alopecia (pseudopelade-like) AD 123:234–237, 1987 Female pattern hair loss JAAD 71:415–428, 2014; SKINmed 11:227–236, 2013; BJD 162:1135–1137, 2010 Focal alopecia – initial sign of female pattern alopecia JAAD 80:1544–1549, 2019 Folliculitis decalvans JAAD 75:1101–1099, 2016 Folliculitis necrotica Folliculitis spinulosa decalvans - pustular variant Frontal fibrosing alopecia (postmenopausal frontal fibrosing alopecia) (S) – a form of lichen planopilaris; scalp, eyebrow, eyelashes, and body hair loss Cutis 102:335–338, 2018; JAAD 79:789–804, 2018; JAAD 75:1101–1099, 2016; Clin Dermatol 32:784–799, 2014; JAAD 71:415–428, 2014; JAAD 70:670–678, 2014; BJD 169:939–941, 2013; BJD 166:440–442, 2012; BJD 166:208–210, 2012; AD 147:1240, 2011; JAAD 63:653–660, 2010; BJD 160:482–501, 2009; BJD 160:75–79, 2009; BJD 159:1–22, 2008; JAAD 57:S15–18, 2007; JAAD 52:55–60, 2005; AD

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139:1363–1368, 2003; AD 137:365–370, 2001; JAAD 36:59–66, 1997; AD 130:770–774, 1994; facial follicular papules BJD 169:217–218, 2013; scarring alopecia of sideburns in men AD 148:1091–1092, 2012 Hereditary hypotrichosis simplex of the scalp – mutation in corneodesmosin BJD 166:36–45, 2012; Ped Derm 19:250–255, 2002; Dermatology 191:139–141, 1995 Hypohidrotic ectodermal dysplasia (loose anagen syndrome) Ped Derm 13:29–32, 1996 Hypotrichosis simplex, hereditary BJD 167:952–954, 2012; Clin in Dermatol 23:47–55, 2005 Hypotrichosis simplex with woolly hair – autosomal recessive; mutation in lipase H JAAD 61:813–818, 2009 Hypotrichosis and vesicles – mutation in DSC3 (desmocollin3) BJD 166:36–45, 2012 Hypotrichosis due to desmoplakin mutations Ped Derm 36:1010– 1011, 2019 Ichthyosis follicularis JAAD 21:351–357, 1989 Increased hair fragility JAAD 71:415–428, 2014   Bubble hair   Trichorrhexis nodosa  Monilethrix   Pili torti   Trichorrhexis invaginata  Trichothiodystrophy Intermittent hair follicle dystrophy JAAD 15:54–60, 1986 Keratosis lichenoides chronica - in children; alopecia of anterior scalp line and eyebrows JAAD 56:S1–5, 2007 Keratosis pilaris atrophicans including ulerythema ophyrogenes Lamellar ichthyosis (S) – autosomal recessive, autosomal dominant Leiner’s disease Lethal acantholytic epidermolysis bullosa – autosomal recessive, universal alopecia, cutaneous and mucosal shedding, skin fragility, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010; JID 130:2680–2683, 2010; BJD 162:138801394, 2010; Dermatol Clin 28:131–135, 2010; mutation in JUP gene Hum Med Genet 20:1811–1819, 2011 Lichen planus – lichen planopilaris (S) (Graham-Little syndrome) JAAD 75:1101–1099, 2016; JAAD 71:415–428, 2014; BJD 160:482–501, 2009; BJD 159:1–22, 2008; JAAD 50:25–32, 2004; Rook p. 1904–1912, 1998, Sixth Edition; Dermatol Clin 14:773–782, 1996; JAAD 22:594–598, 1990; AD Syphilol 5:102–113, 1922 Lichen sclerosus et atrophicus (S) AD 145:1458–1460, 2009; BJD 103:197–200, 1980 Lichen simplex chronicus Clin Dermatol 18:735–743, 2000 Lipedematous alopecia (S)– boggy (“spongy”) scalp with diffuse alopecia; seen particularly in black women Cutis 80:321–324, 2007; JAAD 52:152–156, 2005; AD 138:1517–1518, 2002; J Cutan Pathol 27:49–53, 2000; Dermatology 201:168–170, 2000; Cutis 65:199– 202, 2000; J Cutan Pathol 27:49–53, 2000; AD 134:499–500, 502–503, 1998; AD 130:802–803, 1994; AD 89:819–820, 1964; AD 84:619–622, 1961; Arch Dermatol Syphilol 32:688, 1935 Localized autosomal recessive hypotrichosis Clin in Dermatol 23:47–55, 2005 Localized hereditary hypotrichosis – autosomal dominant; LAH1 – 18q12.1; DSG 4; LAH2 – 3q26.33; LAH3 – 13Q14.11-Q21.32 BJD 166:36–45, 2012 Male pattern alopecia

Marie-Unna hereditary hypotrichosis – autosomal dominant; sparse curly (“funny”) hair (coarse and wiry like horse’s mane); begins at puberty; patches of alopecia, at vertex; affects temporal and frontal scalp lines; starts affects eyebrows, eyelashes, body and pubic hair; 50% with widely spaced incisors; 8p21; mutation in U2HR JAMA Derm 150:567–568, 2014; Ped Derm 28:202–204, 2011; BJD 160:194–196, 2009; Ped Derm 19:250–252, 2002; Derm Wochenschr 82:1167–1178, 1925 Monilethrix – occipital alopecia with increased hair fragility JAAD 71:415–428, 2014; BJD 159:741–743, 2008; JAAD 59:1–22, 2008; Clin in Dermatol 23:6–14, 2005; Ped Derm 16:297–300, 1999; AD 132:577–582, 1996; Scot Med J 3:356–360, 1958; hair that won’t grow long JAAD 53:S130–134, 2005; autosomal recessive/ autosomal dominant; alopecia, keratosis pilaris, xerosis; autosomal recessive - Dsg4 mutation; autosomal dominant KRT81,KRT83, KRT86 BJD 165:425–431, 2011 Non-bullous CIE (congenital ichthyosiform erythroderma) (erythrodermic lamellar ichthyosis) – autosomal recessive – patchy scarring alopecia AD 121:477–488, 1985 Phylloid hypermelanosis – cicatricial alopecia, onychodystrophy, deafness, malformed ear, mental retardation, umbilicated nipples JAAD 19:1037–1044, 1988; Rev Neurol (Paris)95:48–54, 1956 Pili annulati – hair shaft abnormality JAAD 71:415–428, 2014 Pili bifurcate – hypotrichosis Ped Derm 26:169–170, 2009; AD 108:403–407, 1973 Pili torti – autosomal recessive, autosomal dominant, sporadic; isolated defect hair that won’t grow long with increased fragility Ped Derm 33:451–452, 2016; JAAD 71:415–428, 2014; Cutis 84:143– 147, 2009; JAAD 59:1–22, 2008; JAAD 53:S130–134, 2005; Acta DV 53:385–392, 1973; Arch Dermatol Syphilol 26:98–109, 1932; associated with Menkes’ kinky hair syndrome – X-linked recessive; facies including pudgy cheeks, Cupid’s bow upper lip, horizontal eyebrows, diffuse cutaneous hypopigmentation, doughy skin sparse brittle, lusterless, kinky scalp hair; early growth retardation, abnormal hair, focal cerebral and cerebellar degeneration; ATP7A (copper-transporting P-type ATPase) Ann DV 102:269–271, 1980; Pediatrics 50:181–183, 1972; Pediatrics 29:764–779, 1962; Beare syndrome – late onset pili torti with black scalp hair, sparse body and beard hair, patchy alopecia after puberty BJD 64:366–372, 1952; Bjornstad’s syndrome – autosomal recessive, autosomal dominant; congenital sensorineural hearing loss; mutation in BCSIL JAAD 71:415–428, 2014; Eur J Dermatol 10:91–97, 2000; , Bazex syndrome, Crandall’s syndrome - congenital sensorineural hearing loss and hypogonadism, hidrotic ectodermal dysplasia, pseudomonilethrix, oral retinoids Cutis 35:466–470, 1985; Rapp-­Hodgkin syndrome – autosomal dominant, sporadic; anhidrotic ectodermal dysplasia, cleft lip, palate, pili torti, hypodontia, abnormal fingernails, hypospadias J Med Genet 5:269–272, 1968; citrullinemia – hyperammonemia, lethargy Ped Derm 33:451–452, 2016; trichodysplasia-xeroderma – autosomal dominant; xerosis, abnormal hair (alopecia, pili torti, trichorrhexis nodosa) Clin Genet 31:337–342, 1987; trichothiodystrophy – autosomal recessive AD 116:1375– 1384, 1980; Ronchese variants – autosomal recessive, autosomal dominant, sporadic; early onset pili torti; leukonychia, dental abnormalities, keratosis pilaris, dystrophic nails, ichthyosis Arch Dermatol Syphilol 26:98–109, 1932; anorexia nervosa Cutis 57:151–152, 1996; with cleft lip and palate, malformed ears, syndactyly, and mental retardation J Med Genet 25:37–40, 1988; in Rapp-Hodgkin syndrome Oral Surg Oral Med Oral Pathol 67:50–62, 1989; anorexia nervosa Cutis 57:151–152, 1996; monilethrix, woolly hair, mitochondrial disorders, Netherton’s syndrome, Bazex syndrome, longitudinal grooves, trichorrhexis nodosa, citrullinemia, Laron syndrome;

Alopecia   Ectodermal dysplasia associated with pili torti include:    Widely spaced teeth and enamel hypoplasia    Acrofacial dysostosis of the palagonia type    Tooth agenesis   Arthrogryposis    Nail dystrophy Dermatologica 182:184–187, 1991   Clefting   Corneal opacities   Trichodysplasiaxeroderma    Hypohidrotic ectodermal dysplasia   Ichthyosis

PSYCHOCUTANEOUS DISEASE

Acquired pili torti JAMA Derm 155:488, 2019

Trichotemnomania – obsessive cutting of hair JAAD 52:157–159, 2005; Hautarzt 22:335–337, 1971; Hautarzt 19:551–553, 1968

Pili torti and onychodysplasia Dermatologica 182:184–187, 1991 Pohl-Pinkus constriction – increased hair fragility Ghatan, Second Edition, 2002, p.70 Porokeratosis of Mibelli of the scalp Dermatologica 134:269–272, 1967 Progressive patterned scalp hypotrichosis – curly hair, thinning of parietal and vertex scalp, onycholysis, cleft lip and palate JID Symp Proc 8:121–125, 2003 Pseudomonilethrix Pseudopelade of Brocq (S) JAAD 75:1101–1099, 2016; JAAD 71:415–428, 2014; BJD 160:482–501, 2009; BJD 159:1–22, 2008; JAAD 50:25–32, 2004; Curr Prob in Derm VIII:97–136, 1996 Psoriasis - tinea amientacea Clin in Dermatol 37:618–628, 2019; Clin Exp Dermatol 2:137–143, 1977; pustular psoriasis, erythrodermic psoriasis Seborrheic dermatitis JAAD 64:53–63, 2011 Self-healing collodion baby (lamellar ichthyosis of the newborn) Syringolymphoid hyperplasia with alopecia AD 143:921–932, 2007; JAAD 49:1177–1180, 2003; Proc R Soc Med 62:157–159, 2001 Telogen effluvium Cutis 21:543–544, 1978; of the newborn AD 83:175–198, 1961 Trichomalacia – increased hair fragility Trichoptilosis - increased hair fragility Trichorrhexis invaginata (bamboo hair) – increased hair fragility JAAD 71:415–428, 2014 Trichorrhexis nodosa – increased hair fragility JAAD 71:415–428, 2014; JAAD 16:1–24, 1987 Trichothiodystrophy - BIDS, IBIDS, PIBIDS, Pollitt syndrome, Sabinas syndrome, trichothiodystrophy with immune defects; increased hair fragility JAAD 71:415–428, 2014; JAAD 53:S130– 134, 2005; JAAD 20:195–202, 1989 Uncombable hair JAAD 71:415–428, 2014 Vertical alopecia (circumscribed non-scarring alopecia of vertex) Rook p. 2912, 1998, Sixth Edition Woolly hair hypotrichosis – sparse hair BJD 173:865–866, 2015; JAAD 71:415–428, 2014; JAAD 54:165–166, 2006; diffuse partial woolly hair JAAD 59:1–22, 2008; BJD 116:401–405, 1987; woolly hair hypotrichosis – follicular papules (keratosis pilaris) – mutations in LPAR6 (PZRY5) or LIPH genes BJD 165:425–431, 2011 X-linked dominant ichthyosis(Happle’s syndrome) (ConradiHunermann syndrome) – chondrodysplasia punctata, ichthyosis, cataract syndrome; collodion baby or ichthyosiform erythroderma; Blaschko pattern of erythroderma and scaling; plantar hyperkeratosis; resolves with time to reveal swirls of fine scale, linear hyperpigmentation, follicular atrophoderma of arms and legs, cicatricial alopecia; skeletal defects with short stature severe autosomal rhizomelic type; X-linked recessive variant

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Anorexia nervosa – diffuse non-scarring alopecia – telogen effluvium Am J Clin Dermatol 6:165–173, 2005 Delusions of parasitosis - personal observation Factitial alopecia Ped Derm 21:205–211, 2004 Trichodaganomania (compulsive biting of one’s own hair) – alopecia of forearm JAAD 60:689–691, 2009 Trichoteiromania – obsessive rubbing of hair Dtsch Dermatol Ges 1:22–28, 2003; Eur J Dermatol 11:369–371, 2001

Trichotillomania JAAD 76:779–791, 2017; BJD 171:1253–1255, 2014; JAAD 46:807–821, 2002; Curr Prob in Derm VIII:97–136, 1996; J Clin Psychol Psychiatry 32:401–409, 1991; follicular hyperkeratosis BJD 145:1034–1035, 2001

SYNDROMES ACD mental retardation syndrome Am J Med Genet 13:383–387, 1982 Acrocephalopolysyndactyly Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, superficial blisters and desquamation of hands and feet; lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears hooked nose, sparse thin blond hair, frontal alopecia, hypohidrosis, lacrimal duct atresia, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene (encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes BJD 172:276–278, 2015; Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993 Adams-Oliver syndrome – aplasia cutis congenita, distal limb reduction abnormalities, cutis marmorata telangiectasia congenital, central nervous system defects, with cardiovascular malformations BJD 157:836–837, 2007; Am J Med Genet 136A:269–274, 2005; Plast Reconstr Surg 100:1491–1496, 1997; Int J Dermatol 32:52–53, 1993; Eur J Pediatr 126:289–295, 1977 Alopecia-anosmia-deafness hypogonadism syndrome Am J Med Genet 26:925–927, 1987 Alopecia, epilepsy, oligophrenia syndrome of Moynahan Proc R Soc Med 55:411–412, 1962 Alopecia, contractures, mental retardation, dwarfism syndrome Alopecia, keratosis pilaris, cataracts, and psoriasis JAAD 21:351– 357, 1989 Alopecia-mental retardation syndrome BJD 159:748–751, 2008; J Med Genet 20:64–65, 1983 Alopecia, psychomotor epilepsy, pyorrhea, mental retardation Clin Genet 11:13–17, 1977 Alstrom syndrome – dermatologic and pigmentary retinopathy or cone-rod dystrophy; acanthosis nigricans, alopecia, hirsutism; mutation in ALMS1; subcapsular cataracts, cone-rod dystrophy, photophobia, nystagmus, blindness BJD 164:878–880, 2011 Androgen insensitivity syndrome – X-linked recessive Clin in Dermatol 23:47–55, 2005 Anhidrotic ectodermal dysplasia (hypohidrotic ectodermal dysplasia) (Christ-Siemens-Touraine syndrome) J Dermatol 26:44–47, 1999; X-linked recessive – premature aged appearance with soft, dry, finely wrinkled skin, especially around eyes; absent or reduced

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sweating, sparse fine scalp hair, eyebrows, eyelashes, , and total or partial anodontia with conical pointed teeth; mutation in TRAF 6 (TNF receptor-associated factor 6 gene) BJD 168:629–633, 2013; Ped Derm 19:226, 2002; J Med Genet 28:181–185, 1991; autosomal recessive Ped Derm 7:242, 1990; carrier state of X-linked anhidrotic ectodermal dysplasia; mutation in ectodysplasin A (TNF family) Ped Derm 23:396–398,2006 Anhidrotic ectodermal dysplasia with immunodeficiency – conical teeth, sparse hair, hypohidrosis; mutation in NEMO with I-KB gain of function Ped Derm 23:396–398, 2005; JAAD 58:316–320, 2008 AEC syndrome (Hay-Wells syndrome) - ankyloblepharon, ectodermal dysplasia, cleft lip/palate syndrome – blepharitis, eyelid papillomas, periorbital wrinkling; microcephaly, widespread congenital scalp erosions; alopecic ulcerated plaques of scalp, trunk, groin; alopecia of scalp and eyebrows; congenital erythroderma; depigmented patches; syndactyly; bony abnormalities; widely spaced nipples; TP63 mutation BJD 166:134–144, 2012; Ped Derm 28:15–19, 2011; Ped Derm 26:617–618, 2009; AD 141:1591– 1594, 2005; AD 141:1567–1573, 2005; Textbook of Neonatal Dermatology, p.468, 2001; AD 134:1121–1124, 1998; Ped Derm 14:149–150, 1997; BJD 94:287–289, 1976; generalized fissured erosions of trunk BJD 149:395–399, 2003; TP63 mutations seen in AEC syndrome, EEC syndrome, Rapp-Hodgkin syndrome, limb-mammary syndrome, split-hand split-foot malformation type 4, acro-dermatoungual-lacrimal-tooth syndrome AD 141:1567–1573, 2005 Anonychia with bizarre flexural pigmentation – autosomal dominant, absent nails, dry peeling palmoplantar skin, coarse and sparse frontal hair; mottled hyper- and hypopigmentation of the axillae, groin, and natal cleft BJD 92:469–474, 1975 ANOTHER syndrome – alopecia, nail dystrophy, ophthalmic complications, thyroid dysfunction, hypohidrosis, ephelides and enteropathy, respiratory tract infections Clin Genet 35:237–242, 1989; J Pediatr 108:109–111, 1986 Arthrogryposis, renal tubular dysfunction, and cholestasis (ARC) syndrome – ichthyosis, scarring alopecia, ectropion, arthrogryposis of wrist, knee, and hip Ped Derm 22:539–542, 2005 Atrichia congenita with papular lesions – autosomal recessive; infantile hair loss follicular papules; follicular cysts and milia-like lesions; no photophobia Ped Derm 29:519–520, 2012; Clin in Dermatol 23:47–55, 2005; AD 139:1591–1596, 2003; JAAD 47:519–523, 2002; Ped Derm 19:155–158, 2002; Eur J Dermatol 11:375–377, 2001; Dermatology 185:284–288, 1992; Dermatologica 108:114–121, 1954; atrichia with keratin cysts – face, neck, scalp then trunk and extremities; blue cystic papules of face, scalp, neck JID 118:887–890, 2002; JID 117:612–617, 2001; Ann DV 121:802– 804, 1994 Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) – sparse scalp, facial, and body hair, chronic mucocutaneous candidiasis, adrenal insufficiency, hypoparathyroidism, nail dystrophy, keratoconjunctivitis, vitiligo, enamel hypoplasia, mutation in autoimmune regulator gene (AIRE) Ped Derm 24:529– 533, 2007

palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Syndrome Ident 8:6–9, 1982 Basaloid follicular hamartoma syndrome - autosomal dominant; milia, comedone-like lesions, dermatosis papulosa nigra, skin tag-like lesions, hypotrichosis, multiple skin-colored, red, and hyperpigmented papules of the face in periorificial distribution, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes); hypohidrosis AD 144:933–938, 2008; Cutis 78:42–46, 2006; JAAD 49:698–705, 2003; BJD 146:1068–1070, 2002; JAAD 45:644–645, 2001; JAAD 43:189–206, 2000; JAAD 27:237–240, 1992 Basan syndrome (ectodermal dysplasia) - sparse coarse scalp hair, hypohidrosis, nail dystrophy, abnormal dermatoglyphics, dental abnormalities Arch Klin Exp Dermatol 222:546–557, 1965 Bazex-Dupre-Christol-like syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene JAAD 74:437–451, 2016; Ped Derm 25:112–113, 2008; Ped Derm 23:286–290, 2006; Clin in Dermatol 23:47–55, 2005; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Berardinelli-Seip syndrome – autosomal recessive Clin in Dermatol 23:47–55, 2005 Berlin syndrome – no vellus hairs; mottled pigmentation and leukoderma, flat saddle nose, thick lips, fine wrinkling around the eyes and mouth (similar to Christ-Siemens ectodermal dysplasia); stunted growth, bird-like legs, mental retardation Dermatologica 123:227–243, 1961 Bjornstad syndrome (Crandall syndrome) - pili torti with increased hair fragility, short coarse spangled hair; sensorineural deafness; missense mutations in BCS1L gene (necessary for complex III assembly in mitochondria) JAAD 71:415–428, 2014; Ped Derm 30:674–682, 2013; NEJM 356:809–819, 2007; Clin in Dermatol 23:47–55, 2005; JAAD 46:301–303, 2002; Ped Derm 16:220–221, 1999; chromosome 2q34–36 Am J Hum Genet 62:1107–1112, 1998; Crandall’s syndrome – pili torti, sensorineural deafness, hypogonadism JAAD 46:301–303, 2002; J Pediatr 82:461–465, 1973 Brachymetapody syndrome (Tuomaala-Haapanen syndrome) (brachymetapody, anodontia, hypotrichosis, albinoid trait) – albinoid skin – short stature, shortening of all digits but thumbs, hypoplastic maxilla, anodontia, hypotrichosis, hypoplastic breasts and genitalia, strabismus, distichiasis Acta Ophthalmol 46:365–371, 1968 Brown-Crounse syndrome - 1–2 mm papules, plaques, and nodules, diffuse hypotrichosis resembling alopecia areata, basaloid follicular hamartomas, trichoepitheliomas, myasthenia gravis AD 99:478–493, 1969

Bamforth-Lazarus syndrome – autosomal recessive Clin in Dermatol 23:47–55, 2005

Buschke-Ollendorff syndrome - annular plaque with broken hairs JAAD 24:822–824, 1991

Baraitser syndrome (premature aging with short stature and pigmented nevi) – lack of facial subcutaneous fat, fine hair, hypospadias, dental abnormalities, hepatomegaly J Med Genet 25:53–56, 1988; J Med Genet 20:64–75, 1983

Calcitriol-resistant rickets with alopecia

Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft

CAPK – autosomal recessive; arrhythmogenic right ventricular cardiomyopathy, alopecia, palmoplantar keratoderma; mutation of plakoglobin (JUP) BJD 165:917–921, 2011 Carvajal-like syndrome - blisters, woolly hair, palmoplantar kertoderma, cardiac abnormalities; heterozygotes of DSP (desmoplakin) BJD 166:894–896, 2012; Clin Genet 80:50–58, 2011; J Cutan Pathol 36:553–559, 2009

Alopecia Cardio-facio-cutaneous syndrome (Noonan-like short stature syndrome) – autosomal dominant, acanthosis nigricans, xerosis/ ichthyosis, eczematous dermatitis, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, lentigines, nevi of palms and soles, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly short scalp hair and eyebrows and lashes, temporal alopecia, palmoplantar keratoderma of pressure points, hemangiomas, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects BJD 180:172–180, 2019; JAAD 46:161–183, 2002; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992 Cartilage-hair hypoplasia (metaphyseal chondrodysplasia of McKusick) (disproportionate short stature; short limb skeletal dysplasia) – autosomal recessive; dwarfism, mild leg bowing with short limbs, short sparse, lightly colored hair; some with total baldness, immune defects (severe end of the spectrum of severe combined immunodeficiency); mutation in mitochondrial RNA processing; endoribonuclease; 9p13; uniparental disomy BJD 178:335–349, 2018; Ped Derm 22:482–487, 2005; JAAD 54:S8–10, 2006; Clin in Dermatol 23:47–55, 2005; Am J Med Genet 66:378– 398, 1996; Eur J Pediatr 155:286–290, 1996; Eur J Pediatr 142:211–217, 1993; Am J Med Genet 41:371–380, 1991; Bull Johns Hopkins Hosp 116:285–326, 1965 Cataracts, alopecia, and sclerodactyly – ectodermal dysplasia syndrome on the island of Rodrigues Am J Med Genet 32:500–532, 1989 CEDNIK syndrome (cerebral dysgenesis-neuropathy-ichthyosiskeratoderma) – microcephaly; dysmorphic face with small anterior fontanelles; pointed prominent nasal tip, small chin, inverted nipples and long toes, high palate, thick gingivae, cradle cap, sparse brittle coarse hair, scarring alopecia, fixed flexion posture; decreased SNAP 29 protein; mutation in SNARE proteins mediating vesicle trafficking; mutation in ABCA12 gene BJD 164:610–616, 2011; AD 144:334–340, 2008 CHILD syndrome (hemidysplasia, ichthyosiform erythroderma, unilateral limb defects (hypoplasia)) – X-linked dominant; unilateral alopecia; unilateral inflammatory epidermal nevus or unilateral ichthyosiform erythroderma with skeletal abnormalities Clin in Dermatol 23:47–55, 2005; AD 123:503–509, 1987 Chondrodysplasia punctate – X-linked dominant Clin in Dermatol 23:47–55, 2005 Chondroectodermal dysplasia (Ellis van Creveld syndrome) – autosomal recessive; chondrodysplasia, polydactyly, short arms and legs, teeth small and defective, nails dystrophic, hair normal or sparse and brittle; scant or fine hair JAAD 46:161–183, 2002; Ped Derm 18:68–70, 2001; J Med Genet 17:349–356, 1980 Ciliary and superciliary hypotrichosis Cleft lip-palate with ectodermal dysplasia with syndactyly Clouston’s syndrome – mild sensorineural hearing loss, alopecia, thick dystrophic nail plates, palmoplantar keratoderma, photophobia; mutation in GJB2 and GJB6 JAMA Derm 149:1350–1351, 2013 Cockayne syndrome – sparse dry hair in infancy and early childhood JAMA Derm 149:1414–1418, 2013; Ped Derm 20:538– 540, 2003; Textbook of Neonatal Dermatology, p.493, 2001 Coffin-Siris syndrome – autosomal dominant; coarse facial features, sparse scalp hair, bushy eyebrows, absent fifth fingernails and toenails, short distal phalanges, lax joints, delayed eruption of small teeth; microcephaly, retarded growth, skeletal abnormalities Clin in Dermatol 23:47–55, 2005; Clin Genet 26:374–378, 1984; Am J Dis Child 119:433–439, 1970 Complete testicular feminization syndrome - hairless women NEJM 302:198–209, 1980

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Congenital ichthyosis-follicular atrophoderma-hypotrichosis-hypohidrosis syndrome JAAD 63:607–641, 2010; JID 129:862–869, 2009; Am J Med Genet 75:186–189, 1998 Conradi-Hunermann syndrome (chondrodysplasia punctata X-linked dominant) – linear and whorled hyperkeratosis, follicular atrophoderma of forearms in Blaschko distribution; linear atrophic lesions with follicular plugging of scalp; cicatricial alopecia of scalp; patchy patterned alopecia, generalized xerosis; cataracts, chondrodysplasia punctata; asymmetric shortening of long bones epiphyseal stippling, short stature, short limbs, kyphoscoliosis, craniofacial abnormalities); short arms and legs; cataracts; X-linked; mutation in emopamil binding protein (EBP) Ped Derm 31:493–496, 2014; BJD 160:1335–1337, 2009; Curr Prob in Derm VII:143–198, 1995; AD 121:1064–1065, 1985; ichthyotic and psoriasiform lesions (Blaschko hyperkeratotic scaling), nail defects, cicatricial alopecia, follicular pitted scars, skeletal anomalies JAAD 33:356–360, 1995; Hum Genet 53:65–73, 1979; neonatal transient scaly plaques of limbs, trunk, and scalp; scaly rash disappears in months leaving hypo- or hyperpigmented streaks with follicular atrophoderma and patchy scarring alopecia; CDPX2 – X-linked lethal in males; X-linked dominant (mosaic for emopamil-binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309– 1313, 2012 Costello syndrome - warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi, short limbs, failure to thrive; linear papillomatous papules of upper lip BJD 168:903–904, 2013; Clin in Dermatol 23:47–55, 2005; Am J Med Genet 117:42–48, 2003; Ped Derm 20:447–450, 2003 JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977 Cranio-ectodermal dysplasia – short, fine hair, craniofacial abnormalities Birth Defects XI:372–379, 1975 Craniofaciocutaneous syndrome - ulerythema ophryogenes Craniosynostosis, anal anomalies, and porokeratosis (CAP/ CDAGS) – autosomal recessive; craniosynostosis, clavicular hypoplasia, delayed fontanel closure, cranial defects (parietal foramina), deafness, imperforate anus or anterior placement of anus, genitourinary abnormalities (hypospadias and urethrorectal fistula), and skin eruption (porokeratosis-like lesions), mental retardation, scant hair, Staphylococcus aureus infections JAAD 68:881–884, 2013; Am J Hum Genet 77:161–168, 2005; J Med Genet 35:763–766, 1998 Cronkhite-Canada syndrome - lentigo-like macules of face, extremities, and diffuse pigmentation of palms; hyper- and hypopigmented macules of dorsal fingers; gastrointestinal polyposis, malabsorption, alopecia, dystrophic nails JAAD 63:172–174, 2010; AD 135:212, 1999; Cutis 61:229–232, 1998 De Barsy syndrome - sparse hair, thin skin, cutis laxa-like changes, pinched nose Dermatopathia pigmentosa reticularis – autosomal dominant; reticulate pigmentation of trunk, neck, and proximal extremities, alopecia, nail changes (mild onychodystrophy), palmoplantar hyperkeratosis, loss of dermatoglyphics, hyperpigmented tongue, hypo- or hyperhidrosis, non-scarring blisters of dorsal hands and feet, dark areolae, thin eyebrows, Ped Derm 24:566–570, 2007; J Dermatol 24:266–269, 1997; JAAD 26:298–301, 1992; AD 126:935–939, 1990; Dermatol Wochenschr 138:1337, 1958 Dermo-odonto-dysplasia – autosomal dominant; dry skin, small teeth, dysplastic brittle nails, slow growing hair; hair thin with alopecia of vertex Ped Derm 19:226, 2002; Clin Genet 24:58–68, 1983

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Dermotrichic syndrome – X-linked recessive, congenital alopecia universalis (atrichia), generalized ichthyosis, hypohidrosis, vertebral defects, congenital megacolon; no photophobia Am J Med Genet 44:233–236, 1992 Dorfman-Chanarin syndrome (neutral lipid storage disease) – cicatricial alopecia AD 110:261–266, 1974; total alopecia BJD 144:430– 432, 2001 Down’s syndrome – high incidence of alopecia areata Br Med J 1:191–194, 1975; fine sparse hair Dubowitz syndrome – autosomal recessive, erythema and scaling of face and extremities in infancy, sparse blond scalp and eyebrow hair, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities Am J Med Genet 63:277– 289, 1996; Am J Med Genet 47:959–964, 1993 Dwarfism-alopecia-pseudoanodontia- cutis laxa – autosomal recessive; generalized atrichia, unerupted teeth, hyperconvex nails, cutis laxa with fragile skin, dwarfism, deafness, eye anomalies Cienc Cult 34 (Suppl): 705, 1982 Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) – Xq28; hair sparse and dry; loss of eyelashes JAAD 77:1194– 1196, 2017; J Blood Med 5:157–167, 2014; Br J Haematol 145:164–172, 2009; Semin Cut Med Surg 16:72–80, 1997; Clin in Dermatol 23:47–55, 2005; J Med Genet 33:993–995, 1996; Dermatol Clin 13:33–39, 1995; BJD 105:321–325, 1981 Ectodermal dysplasia with corkscrew hair – light lusterless, corkscrew hair with alopecia Ped Derm 19:226, 2002 Ectodermal dysplasia with pili torti and syndactyly – sparse hair, eyebrows and lashes, severe dental dysplasia, yellow thickened nails, lordosis, high arched palate, and syndactyly Ped Derm 16:220–221, 1999 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143– 148, 1999 Ectodermal dysplasia with sparse hair, short stature, hypoplastic thumbs, single upper incisor, and abnormal skin pigmentation Am J Clin Genet 29:209–216, 1988 Ectodermal dysplasia and clefting – alopecia, tooth abnormalities, reticulated hyperpigmentation Ped Derm 28:707–710, 2011 Ectrodactyly, ectodermal dysplasia, cleft lip and palate syndrome (EEC syndrome) – fine, dry, wiry hypopigmented sparse hair, scarring alopecia, peg-shaped teeth, mental retardation; alopecia of scalp, eyebrows, and eyelashes, xerosis, atopic dermatitis, nail dystrophy, hypodontia with peg shaped teeth, reduced sweat glands and salivary glands, syndactyly, mammary gland and nipple hypoplasia, conductive or sensorineural hearing loss, urogenital anomalies, lacrimal duct abnormalities; TP63 mutations BJD 162:201–207, 2010; Ped Derm 20:113–118, 2003; Clin Dysmorphol 5:115–127, 1996; Clin Genet 9:35–40, 1976 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); autosomal dominant; skin peeling;

generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 166:36–45, 2012; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Ehlers-Danlos syndrome Ellis van Creveld syndrome – autosomal recessive Clin in Dermatol 23:47–55, 2005 Encephalocraniocutaneous lipomatosis (Haberland syndrome) – red soft plaque of bulbar conjunctiva (limbal dermoids) (pterygium like lesion) lipomatous hamartomas of scalp and eyelids; linear yellow papules of forehead extending to eyelids; patchy alopecia and ocular christomas; scalp nodules, skin colored nodules, facial and eyelid papules, lipomas, and fibrolipomas; subcutaneous fatty masses of frontotemporal or zygomatic region; nodular tags from outer canthus to tragus; nevus psiloliparus – well-demarcated, smooth alopecic plaque of scalp; mesodermal nevus with paucity of hair and excess fat tissue; appears in encephalocranial lipomatosis Ped Derm 22:206–209, 2005; ophthalmologic manifestations; seizures, mental retardation; mandibular or maxillary ossifying fibromas and odontomas; cranial asymmetry; developmental delay, mental retardation, seizures, spasms of contralateral limbs; unilateral porocephalic cysts with cortical atrophy Ped Derm 35:825–826, 2018; Ped Derm 30:491–492, 2013; Ped Derm 23:27–30, 2006; Ped Derm 22:206–209, 2005; JAAD 47:S196–200, 2002; Am J Med Genet 191:261–266, 2000; JAAD 37:102–104, 1998; BJD 104:89–96, 1981; Arch Neurol 22:144–155, 1970; AD 144:266–268, 2008; Ped Derm 23:27–30, 2006; JAAD 37:102–104, 1998; JAAD 32:387–389, 1995; Ped Derm 10:164–168, 1993; Arch Neurol 22:144–155, 1970 Eosinophilic cellulitis (Wells’ syndrome) Exudative retinopathy with bone marrow failure (Revesz syndrome) – intrauterine growth retardation, reticulate hyperpigmentation of trunk, palms, and soles; fine sparse hair, ataxia with cerebellar hypoplasia, hypertonia, progressive psychomotor retardation J Med Genet 29:673–675, 1992 Eyelid cysts, hypodontia and hypotrichosis JAAD 10:922–925, 1984 Facial hemiatrophy Familial acne conglobata, hidradenitis suppurativa, pili torti, and cataracts Familial focal alopecia Familial gigantic melanocytosis (familial melanopathy with gigantic melanocytes) – diffuse brown hyperpigmentation with raindrop hypopigmentation, light colored scalp and body hair; sparse pubic and axillary hair; large melanocytes filled with late stage melanosomes Int J Derm 44:1010–1015, 2005; Am J Dermatopathol 6:31–34, 1984 Familial mandibuloacral dysplasia (craniomandibular dermatodysostosis) – onset at age 3–5 years; atrophy of skin over hands and feet with club shaped terminal phalanges and acro-osteolysis, mandibular dysplasia, delayed cranial suture closure, short stature, dysplastic clavicles, prominent eyes and sharp nose, alopecia, sharp nose, loss of lower teeth, multiple Wormian bones, acroosteolysis Ped Derm 22:75–78, 2005; BJD 105:719–723, 1981; Birth Defects 10:99–105, 1974

Alopecia Familial partial lipodystrophy, mandibuloacral dysplasia variety – autosomal recessive; short stature, high pitched voice, mandibular and clavicular hypoplasia, dental anomalies, acro-osteolysis, stiff joints, cutaneous atrophy, alopecia, nail dysplasia Am J Med 108:143–152, 2000 Fatal infantile diarrhea with abnormal hair Fibrodysplasia ossificans progressive – multiple neonatal scalp nodules associated with malformation of the great toes (hallux valgus) JAAD 64:97–101, 2011; Flynn-Aird syndrome - skin atrophy, ulceration, alopecia, and dental caries J Neurol Sci 2:161–182, 1965 Follicular atrophoderma Fraser syndrome JAAD 64:53–63, 2011 Fried’s tooth and nail syndrome – fine, short hair, few peg-shaped teeth, nails dystrophic J Med Genet 14:137–139, 1977 GAPO syndrome - growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy; midface hypoplasia; frontal bossing, wide anterior fontanelle, saddle nose, protruding thick lips, low set ears, anti-Mongoloid slant, diffuse scalp hypotrichosis, prominent scalp veins, sparse eyebrows and eyelashes, absent teeth, slightly redundant skin, impacted teeth Ped Derm 27:156–161, 2010; Ped Derm 19:226, 2002; J Craniofac Genet Dev Biol 19:189–200, 1999; Birth Defects 24:205–207, 1988; Am J Med Genet 19:209–216, 1984; Syndr Ident 8:14–16, 1982; Odont Tilster 55:484–493, 1947 Genee-Wiedemann syndrome - acrofacial dysostosis of the predominantly post-axial type - sparse eyelashes Goltz’s syndrome – male mosaic Goltz’s syndrome; blaschko-linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011 Gomez-Lopez-Hernandez syndrome – cerebello-trigeminal-dermal dysplasia – focal scalp alopecia resembling temporal triangular alopecia; cerebellar malformation, trigeminal anesthesia, craniosynostosis; alopecia may be frontal, temporal parietal, or occipital in band-like pattern Am J Med Genet 138A:369–373, 2005 Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa, thin scalp hair with frontotemporal baldness, corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005 Giant axonal neuropathy with kinky light hair – autosomal recessive Clin in Dermatol 23:47–55, 2005 Glucagonoma syndrome (NS) Goltz’s syndrome(focal dermal hypoplasia) (S) – diffuse alopecia AD 145:218–219, 2009; linear alopecia Cutis 53:309–312, 1994; J Dermatol 21:122–124, 1994; asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberrylike papillomas of lips, perineum, acrally, at perineum, buccal mucosa; xerosis; scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones JAAD 25:879–881, 1991 Gomez-Lopez-Hernandez (cerebello-trigeminal-dermal dysplasia) syndrome – parietal alopecia Am J Med Genet 72:34–39, 1997; Brain Dev 1:253–256, 1979 Greither type ectodermal dysplasia – almost total alopecia, loss of teeth, corneal and lens opacities, dystrophic nails, transgradiens palmoplantar keratoderma Arch Klin Exp Dermatol 216:50–62, 1963 HAIR-AN syndrome – acne, muscular physique, alopecia (hyperandrogenism), hidradenitis suppurativa, insulin-­resistance, acanthosis nigricans AD 133:431–433, 1997 Hallermann-Streiff-Francois syndrome (mandibulo-oculofacial syndrome) - scalp margin or sutural alopecia; beak-like nose;

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atrophy over nose and cranial sutures; central facial atrophy and telangiectasia JAAD 50:644, 2004; Ped Derm 13:255–257, 1996; atrophic alopecia Clin Exp Dermatol 14:250–252, 1989 Happle’s syndrome - cicatricial alopecia - X-linked dominant erythrodermic ichthyosis at birth, cataracts, generalized follicular atrophoderma, asymmetric shortening of limbs with chondrodysplasia punctata Ped Derm 18:442–444, 2001; Ped Derm 13:1–4, 1996 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia , coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hartnup’s disease Hay-Wells syndrome – autosomal dominant Clin in Dermatol 23:47–55, 2005 Hereditary hypotrichosis simplex - hair that won’t grow long JAAD 53:S130–134, 2005 Hereditary mucoepithelial dysplasia (dyskeratosis) (Gap junction disease, Witkop disease) – autosomal dominant; non-scarring alopecia; dry rough skin; red eyes, non-scarring alopecia, follicular keratosis (keratosis pilaris), erythema of oral (hard palate, gingival, tongue) and nasal mucous membranes, cervix, vagina, and urethra; perineal and perigenital psoriasiform dermatitis (perineal erythema); hyperpigmented hyperkeratotic lesions of flexures (neck, antecubital and popliteal fossae); esophageal stenosis; keratitis (visual impairment) increased risk of infections, fibrocystic lung disease Ped Derm 29:311–315, 2012; BJD 153:310–318, 2005; Ped Derm 11:133–138, 1994; Am J Med Genet 39:338–341, 1991; JAAD 21:351–357, 1989; Am J Hum Genet 31:414–427, 1979; Oral Surg Oral Med Oral Pathol 46:645–657, 1978 Hidrotic ectodermal dysplasia (Clouston’s syndrome) – pebbly cobblestoned fingertips; alopecia, thick nails Ped Derm 27:651–652, 2010 Hidrotic ectodermal dysplasia (Clouston syndrome) type 2 – scalp hair sparse, fine, pale, and brittle or absent; outer two-thirds of eyebrows; thin eyelashes; GJB6; connexin 30 JID 127:2713–2725, 2007; Clin in Dermatol 23:23–32, 2005; Ped Derm 19:226, 2002; Am J Med Genetics 100:164–168, 2001; Nature Genetics 26:142– 144, 2000; Rook p.394, 1998, Sixth Edition; Can Med Assoc J 21:18–31, 1929 Hutchinson-Gilford syndrome (progeria) – sparse downy scalp hair with eventual generalized alopecia; scleroderma-­like skin changes, wrinkled atrophic skin, hyperpigmentation, abnormal facies Ped Derm 19:226, 2002; Am J Med Genet 82:242–248, 1999; AD 125:540–544, 1989; J Pediatr 80:697–724, 1972 Hypodontia and nail dysgenesis – autosomal dominant; fine brittle hair, few conical and widely spaced teeth, small dystrophic nails, lips everted Oral Surg Oral Med Oral Pathol 39:409–423, 1975 Hypodontia, taurodontism, sparse hair Oral Surg 33:841–845, 1972 Hypogonadism, diabetes mellitus, alopecia, mental retardation and ECG abnormalities Hypohidrosis and diabetes insipidus (Fleck syndrome) – hypohidrosis, hypotrichosis, diabetes insipidus, syndactyly, coloboma, disturbed hematopoiesis Dermatol Wochenschr 132:994–1007, 1955

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Hypohidrotic ectodermal dysplasia – mutation in TRAF6; mutation in TNF- alpha-like path (EDAR, EDARADD, EDA, NEMO) NJD 166:1353–1356, 2012; Clin in Dermatol 23:47–55, 2005 Hypomelia, hypotrichosis, facial hemangioma syndrome (pseudothalidomide syndrome) – sparse silvery blond hair Am J Dis Child 123:602–606, 1972 Hypothyroidism (athyroidal) with spiky hair and cleft palate Hypotrichosis with juvenile macular dystrophy Clin in Dermatol 23:47–55, 2005 Hypotrichosis-lymphedema-telangiectasis syndrome (chronic edema, monoclonal dysglobulinemia and profuse telangiectasia) vascular nevi on palms and soles; autosomal recessive Clin in Dermatol 23:47–55, 2005;Eur J Dermatol 11:515–517, 2001; Ann DV 124:717–720, 1997; palmar telangiectasias Am J Hum Genet 72:1470–1478, 2003; Eur J Dermatol 11:515–517, 2001 HOPP syndrome - hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, lingua plicata, onychogryphosis, ventricular arrhythmias, periodontitis BJD 150:1032–1033, 2004; BJD 147:575–581, 2002 Hypotrichosis and juvenile macular dystrophy – autosomal recessive; mutations in cadherin gene CDH3 Ophthalmol Gen 16:11–15, 1995; Arch Klin Exp Ophthalmol 134:71, 1935 Hypotrichosis with keratosis pilaris Arch Klin Exp Dermatol 210:123–127, 1960 Hypotrichosis with keratosis pilaris and lentiginosis Arch Klin Exp Dermatol 210:123–127, 1960 Hypotrichosis with light colored hair and facial milia Ped Derm 16:108–110, 1999 Hypotrichosis with juvenile retinal macular dystrophy – autosomal recessive; mutation in CDH3 encoding P-cadherin; short sparse scalp hair BJD 153:635–638, 2005; BJD 143:902–904, 2000 Hypotrichosis simplex – bald scalp; corneodesmosin (CDSN) mutation BJD 169:1322–1325, 2013 HID syndrome (hystrix-like ichthyosis with deafness) – autosomal dominant; shark-skin appearance, sensorineural deafness, spiky and cobblestoned hyperkeratosis, neonatal erythroderma, scarring alopecia, occasional punctate keratitis; probably variant of KID syndrome with mutation of connexin 26 (gap junction protein) BJD 146:938–942, 2002 Hutchinson-Gilford progeria syndrome JAMA Derm 150:197–198, 2014 Ichthyosis-cheek-eyebrow syndrome - ICE syndrome – ichthyosis vulgaris, fullness of cheeks, thinning of eyebrows; dysmorphic features, skeletal anomalies Clin Genet 31:137–142, 1987 Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked recessive; hyperkeratotic plaques overlying Achilles tendons; atopic dermatitis; collodion membrane and erythema at birth; ichthyosis, spiny (keratotic) follicular papules (generalized follicular keratoses), non-scarring alopecia totalis, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis, photophobia with progressive corneal scarring; nail dystrophy, paronychia, psychomotor delay, short stature; enamel dysplasia, beefy red tongue and gingiva, angular stomatitis (angular cheilitis), lamellar scales, psoriasiform plaques, palmoplantar erythema; mutation of MBTPS2 (intramembrane zinc metalloproteinase needed for cholesterol homeostasis and endoplasmic reticulum stress response) Clin Exp Dermatol 45:505–507, 2020; JAAD 64:716–722, 2011; BJD 163:886–889, 2010; Ped Derm 26:427–431, 2009; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; Ped Derm 12:195, 1995; AD 125:103–106, 1989; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999; BJD 21:165–189, 1909

Ichthyosis hypotrichosis syndrome Am J Hum Genet 80:467–477, 2007 Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis Clin in Dermatol 23:47–55, 2005 Ichthyosis prematurity syndrome (“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; erythrodermic infant with caseous vernix-like desquamation; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine scaling of scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin (thick vernix caseosa-like covering) (hyperkeratotic scalp) neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4 (FATP4) JAAD 66:606– 616, 2012; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008 Immuno-osseous dysplasia – widespread dermatitis, alopecia, renal disease, short-limbed dwarfism, immunodeficiency with impaired humoral immunity, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation) Ped Derm 23:373–377, 2006; J Pediatr 84:200–203, 1974; J Pediatr 5:675– 684, 1969; spondylo-epithelial dysplasia and mixed immune defect with widespread dermatitis J Med Genet 28:10–17, 1991; J Pediatr 80:1010–1017, 1980 Incontinentia pigmenti (S) – vertex alopecia AD 112:535–542, 1976; pale atrophic hairless patches in stage 4 JAAD 64:508–515, 2011; Hypotrichosis with juvenile macular dystrophy Clin in Dermatol 23:47–55, 2005; AD 139:1163–1170, 2003; JAAD 47:169–187, 2002; JAAD 31:853–857, 1994; J Med Genet 30:53–59, 1993; whorled alopecia JAAD 49:929–931, 2003 IPEX syndrome – X-linked; immune dysregulation, polyendocrinopathy (diabetes mellitus, thyroiditis), autoimmune enteropathy; mutation of FOXP3 gene encodes DNA-binding protein that suppresses transcription of multiple genes involved in cytokine production and T cell proliferation; atopic-like or nummular dermatitis, urticaria, scaly psoriasiform plaques of trunk and extremities, penile rash, alopecia universalis, trachyonychia, bullae; pemphigoid nodularis (bullae and prurigo nodularis) JAAD 55:143–148, 2006; AD 140:466–472, 2004; J Pediatr 100:731–737, 1982 Jackli syndrome – generalized reticulated hyperpigmentation with alopecia, microdontia, and childhood cataracts Johanson-Blizzard syndrome - aplasia cutis congenita of the scalp, sparse hair, deafness, absence of permanent tooth buds, hypoplastic ala nasi, dwarfism, microcephaly, mental retardation, hypotonia, pancreatic insufficiency with malabsorption, hypothyroidism, genital and rectal anomalies Clin Genet 14:247–250, 1978; J Pediatr 79:982–987, 1971 Johnson-McMillin syndrome – autosomal dominant, facial nerve palsy, hearing loss, hyposmia, hypogonadism, microtia, alopecia Bolognia, p.859, 2003 Juvenile macular dystrophy and congenital hypokeratosis - hair that won’t grow long JAAD 53:S130–134, 2005 Keratoderma, hypotrichosis, and leukonychia totalis – dry, brittle, sparse hair Ped Derm 19:226, 2002 Keratosis-ichthyosis-deafness (KID) syndrome – reticulated severe diffuse hyperkeratosis of palms and soles, well marginated, serpiginous erythematous verrucous plaques, perioral furrows, leukoplakia, sensory deafness, photophobia with vascularizing keratitis, blindness Ped Derm 29:349–357, 2012; Ped Derm 23:81–83,2006; Clin in Dermatol 23:47–55, 2005; JAAD 23:385– 388, 1990; AD 123:777–782, 1987; AD 117:285–289, 1981; Keratosis follicularis spinulosa decalvans (Siemens syndrome) (S) – X-linked dominant and autosomal dominant; scarring alopecia

Alopecia

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of scalp and eyebrows, and eyelashes; xerosis, thickened nails, photophobia, spiny follicular papules (keratosis pilaris), scalp pustules, palmoplantar keratoderma, follicular atrophoderma, facial erythema JAAD 58:499–502, 2008; Ped Derm 22:170–174, 2005; JAAD 47:S275–278, 2002; AD 136:235–242, 2000; AD 128:397– 402, 1992; JAAD 16:89–95, 1987; AD 119:22–26, 1983; Arch Dermatol Syphilol 151:384–387, 1926

woolly hair nevus, uncombable hair syndrome, ectrodactyly-ectodermal dysplasia-clefting syndrome, ocular coloboma, hyperhidrotic ectodermal dysplasia, other ectodermal dysplasias JAAD 64:129– 134, 2011

Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, follicular occlusion triad, scalp cysts, nodules (trichilemmal tumors, squamous cell carcinoma), bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation JAAD 69:127–134, 2013; BJD 166:222–224, 2012; Ped Derm 27:651– 652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; JAAD 19:1124–1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915

Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high pitched voice; mutation in RIN2 JAAD 66:842–851, 2012

Keratosis linearis-ichthyosis-congenital sclerosing keratoderma JAAD 63:607–641, 2010; AD 125:103–106, 1989 Kirman syndrome - anhidrosis, total alopecia, and severe mental retardation BJD 67:303–307, 1953 KLICK syndrome (keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; Acta DV 77:225–227, 1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989 Klinefelter’s syndrome – scant hair on beard, trunk, and extremities Klinefelter’s syndrome. Berlin: Springer-Verlag, 1984 Koraxitrachitic syndrome – self-healing collodion baby; heals with mottled reticulated atrophy; alopecia, absent eyelashes and eyebrows, conjunctival pannus, hypertelorism, prominent nasal root, large mouth, micrognathia, brachydactyly, syndactyly of interdigital spaces Am J Med Genet 86:454–458, 1999 Lelis syndrome – acanthosis nigricans with hypohidrosis, hypotrichosis, hypodontia, furrowed tongue, nail dystrophy, palmoplantar keratoderma Genetic Skin Disorders, Second Edition, 2010, pp.94–97 Lipodystrophy associated with mandibuloacral dysplasia – bird-like facies, acro-osteolysis, mottled cutaneous pigmentation, dental abnormalities, skin atrophy, alopecia J Clin Endocrinol Metab 87:776–785, 2002 Lipoid proteinosis - patchy alopecia BJD 151:413–423, 2004; JID 120:345–350, 2003; Hum Molec Genet 11:833–840, 2002; JAAD 39:149–171, 1998; eyelash alopecia due to beaded papules along lash margin Loose anagen syndrome – “hair that won’t grow long”; diffuse thinning of scalp hair with alopecia; blonde or light brown hair; 3-year old Ped Derm 33:507–510, 2016; Ped Derm 31:389–390, 2014; Ped Derm 30:579–583, 2013; JAAD 64:129–134, 2011; AD 145:1123–1128, 2009; JAAD 59:1–22, 2008; JAAD 53:S130–134, 2005; Clin in Dermatol 23:47–55, 2005; JAAD 20:249–256, 1989; loose anagen hairs may be seen with alopecia areata Noonan’s syndrome, nail-patella syndrome, tricho-rhino-phalangeal syndrome,

Lumpy scalp syndrome – autosomal dominant; irregular scalp nodules, deformed pinnae, rudimentary nipples Clin Exp Dermatol 15:240, 1989

Marie Unna’s hereditary hypotrichosis (hereditary hypotrichosis simplex) – autosomal dominant;, coarse sparse scalp hair (”funny hair”) and eyebrows; progressive coarsening JAMA Derm 150:567– 568, 2014; JAAD 59:1–22, 2008; Clin in Dermatol 23:47–55, 2005; BJD 150:837–842, 2004; Ped Derm 19:250–255, 2002; Ped Derm 19:148–150, 2002; BJD 143:811–814, 2000; Dermatology 196:339– 342, 1998; Dermatology 191:139–141, 1995; Clin Genet 32:120– 124, 1987; JID 57:389–400, 1971 Marinesco-Sjogren syndrome – sparse, fine, short, fair, brittle hair, short stature, congenital cataracts, cerebellar ataxia J Ped 65:431–437, 1964 MAUIE syndrome - micropinna, alopecia, ichthyosis, and ectropion JAAD 37:1000–1002, 1997 MC/MR syndrome with multiple circumferential skin creases – multiple congenital anomalies including high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals, posteriorly angulated ears, short stature, hypotonia, pectus excavatum, inguinal and umbilical hernias, scoliosis, hypoplastic scrotum, long fingers, overlapping toes, severe psychomotor retardation, resembles Michelin tire baby syndrome Am J Med Genet 62:23–25, 1996 Meige syndrome JAAD 64:53–63, 2011 Mendes de Costa syndrome – generalized reticulate hyperpigmentation on face and limbs, intraepidermal blisters, microcephaly, mental retardation, atrichia, short conical fingers JAAD 50:S65–69, 2004 Menkes’ kinky hair syndrome – alopecia with increased hair fragility, silvery hair, generalized hypopigmentation, lax skin of brows, neck, and thighs JAAD 71:415–428, 2014; Clin in Dermatol 23:47–55, 2005; Ped Derm 15:137–139, 1998; pili torti Ped Derm 16:220–221, 1999; Pediatrics 50:181–183, 1972 Metaphyseal chondrodysplasia – hypotrichosis Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation (nevus depigmentosus); small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Mitochondrial disease – slow growing, sparse and fragile hair, and hair shaft abnormalities including trichorrhexis nodosa and pili torti JAAD 59:1–22, 2008; J Pediatr 16:459–461, 2003; Pediatrics 103:428–433, 1999 Monilethrix with scalp pruritus, posterior subcapsular cataracts, abnormal facies, severe growth retardation Ped Derm 21:486–490, 2004 Moynahan’s syndrome – autosomal recessive; congenital alopecia, mental retardation, seizures Proc R Soc Med 55:411–412, 1962

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Mucoepithelial dysplasia (gap junction disease) - thin scalp hair Multiple follicular hamartomas with sweat gland and sebaceous differentiation, vermiculate atrophoderma, milia, hypotrichosis, and late development of basal cell carcinomas JAAD 39:853–857, 1998 Myotonic dystrophy - frontal balding - muscle wasting, weakness, cataracts, expressionless face, testicular atrophy JAAD 37:268–269, 1997 Naegeli-Franceschetti-Jadassohn syndrome Clin in Dermatol 23:47–55, 2005 Naxos disease Clin in Dermatol 23:47–55, 2005 Neonatal ichthyosis-sclerosing cholangitis syndrome – autosomal recessive; lamellar ichthyosis, scalp hypotrichosis, scarring alopecia, sclerosing cholangitis; congenital paucity of bile ducts; oligodontia, hypodontia, dysplastic enamel; mutation in CLDN1 (claudin-1; a tight junction component) BJD 170:976–978, 2014; JAAD 63:607–641, 2010; BJD 163:205–207, 2010; Hum Mutat 27:408–410, 2006; Clin in Dermtol 23:47–55, 2005; Gastroenterol 127:1386–1390, 2004; JID 119:70–76, 2002 Netherton’s syndrome - trichorrhexis invaginata (bamboo hair) – increased hair fragility with crew cut appearance Ped Derm 31:90–94, 2014; JAAD 59:1–22, 2008; AD 135:823–832, 1999; BJD 141:1097–1100, 1999; Ped Derm 14:473–476, 1997; Ped Derm 13:183–199, 1996; BJD 131:615–619, 1994; Ped Derm 9:158–160, 1992; AD 78:483–487, 1958 Neutral lipid storage disease (Chanarin-Dorfman disease) – autosomal recessive; focal or diffuse alopecia; congenital non-bullous ichthyosiform erythroderma, collodion baby; seborrheic dermatitislike rash of face and scalp; leukonychia; erythrokeratoderma variabilis-like presentation; mutation in ABHD5 which encodes protein of esterase/lipase/thioesterase subfamily BJD 153:838–841, 2005 Nicolaides-Baraitser syndrome – congenital hypotrichosis, unusual facies (inverted triangular shaped face, low frontal hairline, mild facial hirsutism, deep set eyes, pointed nasal tip, thin nasal bridge, high arched palate, thick lower lip), interphalangeal swelling, short metacarpals (“drumstick fingers”), growth and mental retardation JAAD 59:92–98, 2008 Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, growth retardation, epicanthal folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of face, café au lait macules, vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair 3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000 Noonan’s syndrome – webbed neck, short stature, malformed ears, nevi, keloids, transient lymphedema, ulerythema ophyrogenes, keratosis follicularis spinulosa decalvans JAAD 46:161–183, 2002; Rook p. 3016, 1998, Sixth Edition; Ped Derm 15:18–22, 1998; J Med Genet 24:9–13, 1987 Occipital horn syndrome (Menkes’ disease) – pili torti, soft doughy skin, bony projections from occipital bone of skull; mutation in XLCL, ATP7A JAAD 59:1–22, 2008 Oculo-auricular vertebral syndrome – epibulbar dermoid tumors, abnormal hair, short neck Ped Derm 20:182–184, 2003 Oculocutaneous albinism types I and II – autosomal recessive Clin in Dermatol 23:47–55, 2005 Oculo-dento-osseous (oculo-dento-digital) dysplasia – sparse scalp hair, eyebrows and eyelashes sparse or absent, small closely set sunken eyes, small mouth, enamel hypoplasia producing yellow

teeth, syndactyly, camptodactyly, iris anomalies, hypertelorism autosomal dominant; hypotrichosis, curly hair, nail dystrophy, Clinics in Dermatol 23:23–32, 2005; J Pediatr 63:69–75, 1963 Oculo-osteocutaneous syndrome – sparse, fair hair, limb and digit abnormalities, hypoplastic nipples, abnormal genitalia Ped Derm 19:226, 2002 Odonto-onycho-dermal dysplasia – telangiectatic atrophic patches of face, sparse hair, conical teeth, oligodontia, hyperkeratosis of palms and soles, smooth tongue, dystrophic nails; WNT10A mutation JAAD 65:1066–1069, 2011; Am J Med Genet 14:335–346, 1983 Odonto-onychodysplasia with alopecia – small widely spaced teeth, brittle fingernails, supernumerary nipples, palmoplantar hyperkeratosis Cienc Cult 33 (Suppl):696, 1981 Odonto-trichomelic syndrome – autosomal recessive; severe hypotrichosis, few small conical teeth, hypoplastic or absent areolae, cleft lip, tetramelic dysplasia, short stature Hum Hered 22:91–95, 1972 Olmsted syndrome – diffuse alopecia or sparse hair anteriorly Ped Derm 36:942–943, 2019; JAAD 53:s266–272, 2005; Ped Derm 21:603–605, 2004; Ped Derm 20:323–326, 2003; BJD 136:935– 938, 1997; AD 132:797–800, 1996; AD 131:738–739, 1995; Semin Dermatol 14:145–151, 1995; JAAD 10:600–610, 1984; Am J Dis Child 33:757–764, 1927 Omenn syndrome (familial reticulendotheliosis with eosinophilia) – neonatal exfoliative erythroderma, subacute combined immunodeficiency, diarrhea, hepatosplenomegaly, diffuse alopecia, alopecia of scalp and eyebrows, failure to thrive, lymphadenopathy BJD 178:335–349, 2018; BJD 158:1153–1156, 2008; AD 136:875–880, 2000; Ped Derm 17:91–96, 2000; Ped Derm 14:49–52, 1997 Onycho-trichodysplasia with chronic neutropenia Birth Defects 11:63–66, 1975 Oral-facial-digital syndrome type 1 (Papillon-League-Psaume syndrome) – X-linked dominant; congenital facial milia which resolve with pitted scars; milia of face, scalp, pinnae, and dorsal hands; short stature, hypotrichosis with dry and brittle hair, short upper lip, hypoplastic ala nasi and lower jaw, pseudoclefting of upper lip, hooked pug nose, hypertrophied labial frenulum, bifid or multilobed tongue with small white tumors within clefts, ankyloglossia, multiple soft hamartomas of oral cavity, clefting of hard and soft palate, teeth widely spaced with dental caries, trident hand or brachydactyly, syndactyly, clinodactyly, ulnar deviation of index finger, or polydactyly; hair dry and brittle, alopecic, numerous milia of face, ears, backs of hands, mental retardation with multiple central nervous system abnormalities, frontal bossing, hypertelorism, telecanthus, broad depressed nasal bridge; polycystic renal disease; combination of polycystic renal disease, milia, and hypotrichosis is highly suggestive of OFD 1 Ped Derm 27:669–670, 2010; JAAD 59:1050–1063, 2008; Ped Derm 25:474–476, 2008; Clin in Dermatol 23:47–55, 2005; Ped Derm 9:52–56, 1992; Am J Med Genet 86:269–273, 1999; JAAD 31:157–190, 1994; Ped Derm 9:52–56, 1992; Pediatrics 29:985–995, 1962; Rev Stomatol 55:209–227, 1954 Oral-facial-digital syndrome - X-linked dominant oral-facial-digital syndrome – hairless streaks along Blaschko’s lines Am J Med Genet 85:324–329, 1999 Osteopetrosis-lymphedema-ectodermal dysplasia (OL-HED-ID) syndrome Ped Derm 31:716–721, 2014; AD 144:342–346, 2008; Curr Opin Immunol 16:34–41, 2004; Hum Mol Genet 11:2371–2375, 2002 Pallister-Killian syndrome – short neck; streaks of hypo- and hyperpigmentation, mental retardation, coarse facies with prominent forehead with abnormally high anterior hairline, sparse temporal hair and sparse anterior scalp hair, hypertelorism, short nose with anteverted nostrils, flat nasal bridge, flat occiput, sparse eyelashes,

Alopecia long philtrum with thin upper lip, horizontal palpebral fissure, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i (12p) (tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 24:426– 428, 2007; Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005 Pachyonychia congenita – occasional sparse scalp hair Ped Derm 19:226, 2002; Am J Dermatopathol 19:180–184, 1997 Palmoplantar keratoderma, large ears, sparse hypopigmented scalp hair, frontal bossing Ped Derm 19:224–228, 2002 Papillon-Lefevre syndrome Parry-Romberg syndrome JAAD 64:53–63, 2011 Peeling skin syndrome - personal observation Pili torti, acne conglobata, early onset cataracts BJD 91 (Suppl10):54–57, 1974 Pili torti, defective teeth, webbed fingers JAAD 46:301–303, 2002 POEMS syndrome (Takatsuki syndrome, Crow-Fukase syndrome) osteosclerotic bone lesions, peripheral polyneuropathy, hypothyroidism, and hypogonadism JAAD 21:1061–1068, 1989; Cutis 61:329–334, 1998; cicatricial alopecia with underlying plasmacytoma JAAD 40:808–812, 1999 Poland’s chest wall deformity - breast and pectoralis muscle hypoplasia; absence of axillary hair, ipsilateral syndactyly, dermatoglyphic abnormalities NEJM 378:72, 2017; Plast Reconstr Surg 99:429–436, 1997 Polycystic brain associated with ectodermal dysplasia – thin hair, brain cysts, irregular retinal pigment epithelium, dystrophic nails, dental abnormalities Pediatr Radiol 24:116–118, 1994 Polyostotic fibrous dysplasia – scarring alopecia AD 112:715–719, 1976 Popliteal pterygium syndrome Primary hypogonadism and partial alopecia Progeria syndrome – autosomal dominant Clin in Dermatol 23:47–55, 2005 Proteus syndrome AD 140:947–953, 2004 Pure hair and nail ectodermal dysplasia – autosomal dominant or autosomal recessive; alopecia of scalp; may be generalized; nail dystrophy; mutation in HOXC13 BJD 169:478–480, 2013 PYCR1-related cutis laxa – hair loss, prominent scalp veins, triangular shaped face, microcephaly, short stature, hypermobility of joints, thin atrophic skin, wrinkled skin, muscle weakness, finger contractures Dtsch Arztebl Int 16:489–496, 2019 Rapp-Hodgkin hypohidrotic ectodermal dysplasia - autosomal dominant; alopecia of wide area of scalp in frontal to crown area, short eyebrows and eyelashes, coarse wiry sparse hypopigmented scalp hair, sparse body hair, scalp dermatitis, ankyloblepharon, syndactyly, nipple anomalies, cleft lip and/or palate; nails narrow and dystrophic, small stature, hypospadias, conical teeth and anodontia or hypodontia; distinctive facies, short stature JAAD 53:729–735, 2005; Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968 Reactive arthritis Reflex sympathetic dystrophy JAAD 58:320–322, 2008; JAAD 35:843–845, 1996; JAAD 22:513–520, 1990; Arch Neurol 44: 555–561, 1987 Robert’s syndrome (pseudothalidomide syndrome) - hypotrichosis, growth retardation, cleft lip, mild facial port wine stain JAAD 37:523–549, 1997 Romberg syndrome (facial hemiatrophy) – frontoparietal alopecia Arch Neurol 39:44–46, 1982

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Rombo syndrome – papules and cysts of the face and trunk, basal cell carcinomas, vermiculate atrophoderma, milia, sparse beard hair and thin eyebrows, trichoepitheliomas, peripheral vasodilatation with cyanosis BJD 144:1215–1218, 2001; JAAD 39:853–857, 1998; JAAD 28:1011–1014, 1993; Acta DV 61:497–503, 1981 Rosselli-Gulinetti syndrome (ectodermal dysplasia) – autosomal recessive, hypohidrosis, fine, dry, sparse scalp hair, dystrophic nails and teeth, cleft lip and palate, syndactyly, defects of external genitalia Ped Derm 19:226, 2002; J Plast Surg 14:190–204, 1961 Rothmund-Thomson syndrome – poikiloderma, photosensitivity (early erythema, edema, blistering of face); sparse hair, sparse eyebrows, small stature, palmoplantar keratoderma, skeletal anomalies, cataracts, osteosarcoma in 30% JAAD 67:1113–1127, 2012; Curr Prob Derm 14:41–70, 2002; BJD 139:1113–1115, 1998; Ped Derm 6:325–328, 1989; Ped Derm 6:321–324, 1989; JAAD 17:332–338, 1987; mutations in DNA helicase gene RECQL4 Nat Genet 22:82–84, 1999; Ped Derm 18:210–212, 2001; Am J Med Genet 22:102:11–17, 2001; Ped Derm 18:210–212, 2001; Ped Derm 16:59–61, 1999; Dermatol Clin 13:143–150, 1995; JAAD 27:75–762, 1992; JAAD 17:332–338, 1987; Arch Ophthalmol (German) 4:159, 1887 Sakati syndrome – patchy alopecia with atrophic skin above ears, submental linear scars, acrocephalopolysyndactyly, short limbs, congenital heart disease, abnormally shaped low-set ears, ear tag, short neck with low hairline J Pediatr 79:104–109, 1971 Salamon’s syndrome - woolly hair, hypotrichosis, dystrophic nails, ophthalmologic abnormalities, everted lower lip, outstanding ears Arch Klin Exp Dermatol 220:564–575, 1964 SASH1 related lentigines, hyper- and hypopigmentation, alopecia, nail dystrophy, palmoplantar keratoderma, skin cancer BJD 177:945–959, 2017 Satoyoshi syndrome – alopecia areata (universalis) with progressive painful intermittent muscle spasms, diarrhea or unusual malabsorption, endocrinopathy with amenorrhea (hypothalamic dysfunction), very short stature, flexion contractures, skeletal abnormalities Ped Derm 18:406–410, 2001; AD 135:91–92, 1999 Schopf-Schulz-Passarge syndrome - eyelid cysts (apocrine hidrocystomas), palmoplantar keratoderma, hypotrichosis, decreased number of teeth, brittle and furrowed nails; mutation in WNT10A BJD 171:1211–1214, 2014; Ped Derm 30:491–492, 2013; JAAD 65:1066–1069, 2011; Acta DV 88:607–612, 2008; AD 140:231–236, 2004; BJD 127:33–35, 1992; JAAD 10:922–925, 1984; Birth Defects XII:219–221, 1971 Seckel’s syndrome – autosomal recessive; hair sparse and prematurely gray, growth retardation, beak-like nose, large eyes, skeletal defects Am J Med Genet 12:7–21, 1982 Short anagen syndrome – short blond hair Ped Derm 35:388–391, 2018; Ped Derm 28:133–134, 2011; JAAD 53:S130–134, 2005; J Clin Dermatol 2:30–32, 1999; hypotrichosis; hair that won’t grow long JAAD 63:1092–1093, 2010; JAAD 53:S130–134, 2005; BJD 143:612–617, 2000; differential diagnosis includes trichodental syndrome (short anagen syndrome with hypodontia) BJD 116:259– 263, 1987; also Noonan syndrome, loose anagen syndrome, peeling skin syndrome, telogen effluvium Sotos syndrome Clin in Dermatol 23:47–55, 2005 Sparse brittle hair and spondyloepimetaphyseal dysplasia Sternal cleft with hemagiomas of the face and anterior trunk Swirled alopecia (Blaschko-esque) in:   Aplasia cutis congenita   Conradi’s syndrome Human Genetics 70:200–206, 1985   Oral facial digital syndrome JAAD 31:157–190, 1994 Syringomyelia, syringobulbia Dermatol Wochenschr 143:543–545, 1961

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Taurodontism, oligodontia, sparse hair Birth Defects 11:39–50, 1975 Tay syndrome – brittle and sparse hair, progeric appearance, low birthweight Ped Derm 19:226, 2002 T-cell immunodeficiency, congenital alopecia, and nail dystrophy Clin in Dermatol 23:47–55, 2005 Thumb deformity and alopecia Treacher-Collins syndrome (mandibulofacial dysostosis) – partial or total alopecia of lower eyelashes, scarring alopecia, characteristic facies, malformed pinnae, extension of scalp hair onto cheeks; blind fistulae between ear and angle of mouth Am J Dis Child 113:405– 410, 1967 Tricho-dental dysplasia JAAD 53:S130–134, 2005 Trichodysplasia with xeroderma Trichodentoosseous syndrome – autosomal dominant Clin in Dermatol 23:47–55, 2005 Tricho-oculo-dermo-vertebral syndrome (Alves syndrome) – dry, sparse, brittle hair, dystrophic nails, plantar keratoderma, short stature, cataracts Am J Med Genet 46:313–315, 1993 Tricho-odonto-onychodysplasia syndrome – autosomal recessive; alopecia of vertex; hair dry, brittle, and sparse, curly, easily plucked, enamel hypoplasia of teeth, nail dystrophy, supernumerary nipples, palmoplantar hyperkeratosis, melanocytic nevi Ped Derm 19:226, 2002; Am J Med Genet 15:67–70, 1983 Tricho-odonto onycho-ectodermal dysplasia (linear dermal hypoplasia) - hypotrichosis, hypodontia, focal linear dermal hypoplasia of the tip of the nose, irregular hyperpigmentation of the back, bilateral amastia and athelia, nerve hearing loss AD 122: 1047–1053, 1986 Trichorhinophalangeal syndrome type I – autosomal dominant; slow growing hair, receding frontotemporal hairline with high bossed forehead; thin nails, koilonychias, leukonychia, facial pallor, pear-shaped nose with bulbous nose tip, wide long philtrum, thin upper lip, triangular face, receding chin, tubercle of normal skin below the lower lip, protruding ears, distension and deviation with fusiform swelling of the PIP joints; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, lateral eyebrows sparse and brittle,, dense medially, bone deformities (hands short and stubby), cone-shaped epiphyses of bones of hand, lateral deviation of interphalangeal joints, flat feet, hip malformations, high arched palate, supernumerary teeth, dental malocclusion, mild short stature; hypotonia, deep voice, recurrent respiratory infections, hypoglycemia, diabetes mellitus, hypothyroidism, decreased growth hormone, renal and cardiac defects, mutation in zinc finger nuclear transcription factor (TRPS1 gene) Cutis 89:56, 73–74, 2012; BJD 163:420–423, 2010; Ped Derm 26:171–175, 2009; Ped Derm 25:557–558, 2008; BJD 157:1021–1024, 2007; AD 137:1429–1434, 2001; JAAD 31:331–336, 1994; Hum Genet 74:188–189, 1986; Helv Paediatr Acta 21:475–482, 1966 Tricho-rhino-phalangeal syndrome type II (Langer-Giedion syndrome) – facies, bulbous nose, and sparse hair as in TRPS-I microcephaly, loose, redundant skin, exostoses, mental retardation, microcephaly, multiple skeletal exostoses; EXT gene BJD 171:1581–1583, 2014; Am J Med Genet 19:81–111, 1984; Birth Defects X:147–164, 1974 Trichothiodystrophy syndromes - BIDS, IBIDS, PIBIDS – brittle hair, premature aging, sexual immaturity with sparse or absent axillary, pubic, and body hair, few vibrissae and otic hair, sparse or absent eyelashes and eyebrows, fragile hair, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; socially engaging personality; mutation in one of 3 DNA repair genes (XPB, XPA, TTDA, or TTDN1 Ped Derm 32:865–866,

2015; JAAD 63:323–328, 2010; Ped Derm 25:264–267, 2008; JAAD 52:224–232, 2005; JAAD 44:891–920, 2001; Ped Derm 14:441– 445, 1997; JAAD 22:705–717, 1990; Sabinas syndrome – brittle hair, impaired intelligence, decreased fertility/ BIDS (short stature)/ IBIDS (ichthyosis)/PIBIDS (photosensitivity)/Marinesco-Sjogren syndrome – cerebellar ataxia, physical and mental retardation, dysarthria, cataracts, fine brittle hair; PIBIDS and chronic neutropenia, recurrent infections, folliculitis, conjunctivitis; Pollitt syndrome; Tay syndrome; Amish brittle hair syndrome; non-photosensitive trichothiodystrophy with mental retardation and/or decreased fertility JAAD 59:1–22, 2008 Turner’s syndrome – alopecia areata; frontal alopecia JAAD 74:231–244, 2016 Vohwinkel’s syndrome – occasional diffuse or scarring alopecia Ped Derm 19:226, 2002 Vogt-Koyanagi-Harada syndrome – alopecia areata or diffuse hair loss Ped Derm 31:99–101, 2014 Waardenburg syndrome types I and IIA – autosomal dominant Clin in Dermatol 23:47–55, 2005 Wallenberg syndrome Werner’s syndrome (pangeria) – graying of temples in teenage years with progressive alopecia; sparse or absent pubic and axillary hair Clin in Dermatol 23:47–55, 2005; Medicine 45:177–221, 1966 Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – autosomal recessive, sparse hair, generalized lipoatrophy, macrocephaly, premature aging, wide open sutures, aged and triangular face with hypoplasia of facial bones, persistent fontanelles, prominent scalp veins, growth retardation, low set ears, beak shaped nose, neonatal teeth, slender limbs, large hands and feet with long fingers, large penis, pseudohydrocephalus, psychomotor retardation Ped Derm 22:75–78, 2005; J Med Genet 34:433–437, 1997; Eur J Pediatr 130:65–70, 1979; Eur J Pediatr 124:101–111, 1977 Woodhouse-Sakati syndrome – autosomal recessive; triangular shaped face with prominent forehead, large low set ears, dystonia, hypotrichosis, with sparse eyebrows and eyelashes; alopecia, hypogonadism, diabetes mellitus, mental retardation, sensorineural deafness, extrapyramidal signs, low insulin-like growth factor 1; must be differentiated from congenital hypotrichosis; mutation in C2orf37 Ped Derm 31:83–87, 2014; Am J Med Genet 143:149–160, 2007; J Med Genet 20:216–219, 1983 Woolly hair, alopecia, premature loss of teeth, nail dystrophy, reticulate acral hyperkeratosis, facial abnormalities BJD 145:157– 161, 2001 X-linked adrenoleukodystrophy (Addisonian) JAAD 860–861, 2012 X-linked ectodermal dysplasia with immunodeficiency – NEMO mutation; erythroderma, alopecia, red scaly scalp, frontal bossing, periorbital wrinkling, intertrigo, thick everted lower lip AD 144:342– 346, 2008; Curr Opin Allergy Clin Immunol 5:513–518, 2005; Immunol Rev 203:21–37, 2005; Textbook of Neonatal Dermatology, p.266, 2001; J Pediatr 114:600–602, 1989 X-linked hypohidrotic ectodermal dysplasia, mosaicism – V-shaped hypopigmented linear lesions, patchy hypotrichosis, abnormal teeth Ped Derm 24:551–554, 2007 XXYY syndrome – features of Klinefelter’s; sparse body hair; also multiple angiomas, acrocyanosis, and premature peripheral vascular disease AD 94:695–698, 1966 Xeroderma pigmentosum, group D – fractured hair BJD 161:1379– 1383, 2009 Yunis-Varon syndrome (dysplastic clavicles, sparse hair, digital anomalies) – anonychia Am J Dis Child 134:649–653, 1980 Zunich neuroectodermal syndrome Ped Derm 13:363–371, 1996

Alveolar Hemorrhage

TOXINS Arsenic poisoning – acute BJD 149:757–762, 2003; acute arsenic beer poisoning – garlic odor of skin; yellow-­brown pigment, sore tongue, photophobia, alopecia, shedding nails BJD 165:209–210, 2011; anagen effluvium Bismuth Boric acid (pesticides) - anagen effluvium JAAD 44:599–602, 2001 Chemical scalp burn – hair highlighting with persulfate and hydrogen peroxide; red plaque with granulation tissue Ped Derm 27:74–78, 2010 Eosinophilia myalgia syndrome (l-tryptophan related) – morphea, urticaria, papular lesions; arthralgia BJD 127:138–146, 1992; Int J Dermatol 31:223–228, 1992; Mayo Clin Proc 66:457–463, 1991; Ann Int Med 112:758–762, 1990; JAAD 23:1063–1069, 1990

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Post-operative alopecia (pressure-induced alopecia) JAAD 57:550–551, 2007; Cutis 54:21–22, 1994 (S and NS); Ped Derm 10:32–33, 1993; surgery in Trendelenburg position; cardiac surgery J Thorac Cardiovasc Surg 71:342–345, 1976; Anesthesiology 25:869–871, 1964 Radiodermatitis (S and NS) - acute radiation gives anagen effluvium; chronic radiation dermatitis; acute or chronic JAAD 54:28–46, 2006 Pseudoglucagonoma syndrome – periorificial erythema, crusted migratory plaques, hair loss, brittle nails, diarrhea, poor weight gain, onycholysis; associated with cirrhosis, celiac disease inflammatory bowel disease, small cell lung cancers Am J Med 126:387–389, 2013 Scalp vein infusion – extensive cicatricial alopecia Clin Exp Dermatol 4:197–199, 1979

Mercury and other heavy metals (lead, cadmium) - anagen effluvium

Sleep-related rhythmic movement disorder Ped Derm 37:350–351, 2020

Phenyl glycidyl ether inhalation J Toxicol Environ Health 3:859–869, 1977

Sock alopecia - personal observation

Selenium toxicity – transverse white nail bands; exfoliative scalp dermatitis with hair loss, dizziness, fatigue, amenorrhea, nausea and vomiting, joint pain; “Total Body Formula” dietary supplement JAAD 63:168–169, 2010 Thallium - anagen effluvium JAMA Derm 152:724–726, 2016; JAAD 50:258–261, 2004; nausea, vomiting, stomatitis, painful glossitis, diarrhea; severe dysesthesias and paresthesias in distal extremities (polyneuropathy), facial rashes of cheeks and perioral region, acneiform eruptions of face, hyperkeratosis of palms and soles, hair loss, Mees’ lines AD 143:93–98, 2007

TRAUMA Accidental trauma Balance beam alopecia AD 114:968, 1978 Burns (S and NS) - thermal, electrical, radiation, chemical Clin Dermatol 18:735–743, 2000 Carpenter’s nodules - personal observation Ceramic flat irons – hair breakage JAAD 62:145–147, 2010 Radiation – scarring alopecia Cutis 81:147–153, 2008

Surgical embolization – occipital scalp necrosis and scarring Surg Neurol 25:357–366, 1988 Tattoo removal JAAD 64:53–63, 2011 Traction alopecia (NS and S) JAAD 75:606–611, 2016; Cutis 89:213–216, 2012; BJD 157:981–988, 2007; Curr Prob in Derm VIII:97–136, 1996; Dermatol Clin 6:387–395, 1988; frontal traction alopecia from religious hair décor Ped Derm 28:336–338, 2011

VASCULAR Atherosclerosis – loss of hair of lower legs Capillary malformation-arteriovenous malformation syndrome – telangiectasias of chest; central punctate red spots; nevus anemicus surrounded by pale halo; absence of vellus hairs over the AVM BJD 172:450–454, 2015 Involuted hemangioma personal observation Sinus pericranii – alopecic red or blue nodule of scalp JAAD 46:934–941, 2002 Temporal arteritis (S) – alopecia of affected area of scalp Lancet 359:1199, 2002; BJ Rheum 36:814–816, 1997

Cephalohematoma Child abuse Ped Derm 23:311–320, 2006 Cosmetic alopecia mechanica (hairdressing procedures) – hair straightening, brush roller alopecia, hot comb alopecia Rook p. 2927, 1998, Sixth Edition; Dermatol Clin 6:387–395, 1988;

ALVEOLAR HEMORRHAGE

Fetal intravenous needle (S) Clin Exp Dermatol 4:197–199, 1979

Patients present with dyspnea, cough, hemoptysis, and new alveolar infiltrates

Fetal scalp electrode (S) Am J Obstet Gynecol 129:351–360, 1977; perinatal fetal scalp monitor - scarring alopecia AD 135:697–703, 1999 Fluoroscopically guided vascular surgery - non-scarring alopecia AD 135:1555–1556, 1999 Forceps delivery Frictional alopecia Head banging – in sleep-related rhythmic movement disorder Ped Derm 37:350–351, 2020 Head injuries Mechanical trauma (S and NS) – pressure, brush alopecia, hair weaving, massage, water slides, gymnasts, breakdancing, headphones JAAD 81:1021–1023, 2019; Cutis 67:399–400, 2001 Neonatal occipital alopecia – rubbing

NEJM 367:1547, 2012; Cleveland Clin J Med 75:258–280, 2008

VASCULITIS OR CAPILLARITIS Acute lung-graft rejection Anti-glomerulo-basement membrane (GBM) disease Antiphospholipid antibody syndrome Behcet’s syndrome Eosinophilic granulomatosis with polyangiitis Combined anti-GBM disease and ANCA-associated disease (antimyeloperoxidase) Connective tissue disorders Cryoglobulinemia, mixed (IgG and IgM)

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Drug hypersensitivity  Hydralazine  Nitrofurantoin  Penicillamine  Phenytoin  Propylthiouracil Goodpasture’s syndrome Granulomatosis with polyangiitis ANCA + (antiproteinase 3) Henoch-Schonlein purpura Idiopathic pulmonary hemosiderosis (with delayed anti-GBM disease) Idiopathic thrombocytopenic purpura IgA nephropathy Isolated pauci-immune pulmonary capillaritis Lupus erythematosus, systemic – with or without ANCA, anti-GBM antibody, or antiphospholipid antibody

 LVEOLAR BLEEDING ASSOCIATED A WITH ANOTHER PROCESS OR CONDITION Angiosarcoma, pulmonary Aspergillosis, invasive Bacterial pneumonia Cytomegalovirus infection Diffuse alveolar damage Hantavirus infection Herpes simplex virus infection High altitude pulmonary edema Kaposi’s sarcoma Legionellosis Leptospirosis Leukemia – acute promyelocytic leukemia

Microscopic polyangiitis – renal and pulmonary involvement only or multisystem; ANCA+(antimyeloperoxidase)

Lymphangiography

Mixed connective tissue disease

Multiple myeloma

Pauci-immune glomerulonephritis, immune complex-associated glomerulonephritis

Mycoplasma pneumonia infection

Progressive systemic sclerosis

Pulmonary embolism

Urticaria-vasculitis syndrome

Sarcoid

Thrombotic thrombocytopenic purpura

Serratia marcescens pneumonia – red sputum from alveolar flooding of the organism (pseudo-hemoptysis)

 LAND PULMONARY HEMORRHAGE WITHOUT B CAPILLARITIS OR VASCULITIS Anticoagulants, antiplatelet agents, or thrombolytics Crack cocaine Detergents Disseminated intravascular coagulation Drugs   All-trans retinoic acid  Amiodarone  Bleomycin  Diphenylhydantoin  D-penicillamine  Gold  Haloperidol  Infliximab  Methotrexate  Mitomycin  Montelukast  Nitrofurantoin  Sirolimus  Zafirlukast Idiopathic pulmonary hemosiderosis HIV infection

Lymphangioleiomyomatosis

Pulmonary capillary hemangiomatosis

Tuberous sclerosis

INFECTIONS Aspergillosis - pulmonary or systemic infection with glomerulonephritis or interstitial nephritis Cryptococcosis Cytomegalovirus infection – pulmonary or systemic infection with glomerulonephritis or interstitial nephritis HIV disease Legionnaire’s disease Leptospirosis - pulmonary or systemic infection with glomerulonephritis or interstitial nephritis Paragonimiasis - pulmonary or systemic infection with glomerulonephritis or interstitial nephritis Staphylococcal sepsis - pulmonary or systemic infection with glomerulonephritis or interstitial nephritis Streptococcal sepsis - pulmonary or systemic infection with glomerulonephritis or interstitial nephritis Zygomycosis - pulmonary or systemic infection with glomerulonephritis or interstitial nephritis

Infective endocarditis

OTHER DISORDERS

Mitral stenosis or mitral regurgitation

Acute tubular necrosis

Pesticides

Advanced diabetic nephropathy

Pulmonary veno-occlusive disease

Focal and segmental glomerulosclerosis

Trimellitic anhydride (toxin)

Hemolytic uremic syndrome with glomerular thrombotic microangiopathy

Angioedema Lung cancer with associated glomerular disease Malignant hypertension with glomerular fibrinoid necrosis Membranoproliferative glomerulonephritis Multiple pulmonary emboli with coexistent renal disease (membranous glomerulopathy) Silica dust exposure with anti-GBM antibody or ANCA Transplantation – lung or stem-cell transplantation Uremic pneumonitis with advanced renal failure

ANGIOEDEMA JAAD 53:373–388, 2005

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Allergic contact dermatitis Allergic contact urticaria JAAD 53:373–388, 2005; Clin Dermatol 15:619–672, 1997 Antibody against the C1 esterase inhibitor without associated disease Allergic angioedema JAAD 53:373–388, 2005 Angioedema associated with idiopathic or chronic urticaria JAAD 53:373–388, 2005

release from basophils and mast cells; may be caused by ciprofloxacin, amphotericin B, rifampicin, and teicoplanin JAAD 60:890– 891, 2009; Postgrad Med 75:41–43, 1999

EXOGENOUS AGENTS Aquagenic urticaria JAAD 53:373–388, 2005 Acquired cold urticaria JAAD 49:714–716, 2003 Betel nut (areca nut) chewing – betel quid (areca nut, leaf of betel pepper, slaked lime paste from shells, coral, or limestone) autonomic and psychoneurologic effects; cholinergic activation, flushing, tachycardia, warmth, euphoria, alertness, hypotension, angioedema, hyperhidrosis, myocardial infarction Clin Toxicol 39:355– 360, 2001 Cold urticaria JAAD 53:373–388, 2005; J Clin Lab Med 74:902–910, 1969 Foods – peanuts, shellfish, milk, eggs, tree nuts, and foods which cross-react with latex (kiwi, banana, avocado, chestnut) JAAD 53:373–388, 2005; peanut allergy – urticaria, angioedema, anaphylaxis JAAD 66:136–143, 2012 Henna (Lawsonia inermis) Poster Session, European Academy of Dermatology and Venereology, 2002 Solar urticaria JAAD 59:909–920, 2008; JAAD 53:373–388, 2005; Photodermatol Photoimmunol Photomed 21:226–228, 2005; Arch Dermatol Res 220:19–37, 1964

Autoimmune progesterone urticaria

INFECTIONS

Complement deficiencies Ped Derm 28:494–501, 2011

Angioedema associated with infections and infestations JAAD 53:373–388, 2005

Lupus erythematosus - systemic lupus erythematosus JAAD 7:255–264, 1982

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Ascariasis

Serum sickness - personal observation

Caterpillar envenomation - Spanish pine processionary caterpillar (Thaumetopoea pityocampa) – urticaria, angioedema, anaphylaxis JAAD 62:1–10, 2010; Cutis 80:110–112, 2007

DRUGS

Insect venoms JAAD 53:373–388, 2005

Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema Cutis 91:30–35, 2013; NEJM 355:295, 2006; JAAD 53:373–388, 2005; AD 116:902–905, 1980

Loiasis

Angiotensin converting enzyme in face and oral mucosa; not associated with urticaria BJD 136:153–158, 1997 Clopidogrel – morbilliform eruption; angioedema Curr Allergy Asthma Rep 11:52–57, 2011

Parvovirus B19 – neonatal angioedema due to intrauterine infection with Parvovirus B19 BJD 143:428–430, 2000

INFLAMMATORY DISORDERS Eosinophilic myositis/perimyositis JAAD 37:385–391, 1997

Drug reaction JAAD 53:373–388, 2005 Estrogen-dependent inherited angioedema J Allergy Clin Immunol 106:546–550, 2000

METABOLIC DISEASES

Fidaxomicin (macrolide antibiotic) – facial, tongue, and throat swelling Clin Inf Dis 58:537–538, 2014

Acquired C 1 esterase inhibitor deficiency Am J Med 95:169–175, 1993; B-cell lymphoma BJD 146:343–344, 2002

Leukotriene antagonist (montelukast) administration concurrently with aspirin JAAD 53:373–388, 2005

Gleich’s syndrome (episodic angioedema with eosinophilia) (fluid retention syndrome) – angioedema, urticaria, fever, periodic weight gain, eosinophilia, oliguria, increased IgM AD 141:633–638, 2005; Am J Nephrol 24:154–161, 2001; JAAD 20:21–27, 1989; NEJM 310:1621–1626, 1984; swollen feet BJD 159:738–740, 2008; NEJM 310:1621–1626, 2008; JAAD 53:373–388, 2005; Clin Exp Immunol 82:38–43, 1990; NEJM 310:1621–1626, 1984

NSAID (including aspirin)-induced angioedema JAAD 53:373–388, 2005 Radiocontrast media JAAD 53:373–388, 2005 Tissue plasminogen activator, intravenous (t-PA) NEJM 382:2449, 2020 Vancomycin – red man syndrome, acute erythroderma, angioedema, hypotension, dyspnea, chest pain – due to histamine

Graves’ disease JAAD 48:641–659, 2003

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

NEOPLASTIC DISEASES Angiosarcoma – recurrent angioedema BJD 143:1346–1348, 2000 Waldenstrom’s macroglobulinemia

PARANEOPLASTIC DISORDERS Leukemia – chronic lymphocytic leukemia Ghatan, Second Edition, 2002, p.122; acute lymphoblastic leukemia with eosinophilia Ped Derm 20:502–505, 2003 Lymphoma - angioimmunoblastic T-cell lymphoma Indian J Otolaryngol Head Neck Surg 71 (Suppl 1):96–99, 2019 Monoclonal gammopathy Myeloma Necrobiotic xanthogranuloma with paraproteinemia – antibody mediated decreased levels of C1 esterase inhibitor Hautarzt 45:339–343, 1994

PRIMARY CUTANEOUS DISEASES Angioedema (idiopathic acquired angioedema) – lips, eyelids, genitalia BJD 154:542–545, 2006; JAAD 53:373–388, 2005; JAAD 25:155–161, 1991 Cholinergic angioedema AD 123:462–467, 1987 Cholinergic urticaria Cyclic edema Urticaria BJD 154:542–545, 2006; Urticaria multiforme – large polycyclic and annular wheals with dusky centers, acral and facial angioedema Ped Derm 28:436–438, 2011

SYNDROMES AHA syndrome (arthritis or arthralgia, hives, angioedema) Rheumatol Int 7:277–279, 1987

98:44–46, 1983; Am J Med Genet 9:307–315, 1981; J Allergy Clin Immunol 50:174–182, 1972

VASCULAR DISORDERS Angioedema associated with urticarial vasculitis JAAD 53:373–388, 2005; Medicine 74:24–41, 1995 Capillary leak syndrome JAAD 32:364–6, 1995 Cutaneous polyarteritis nodosa – angioedema; livedo reticularis, lower leg ulcers JAMA Derm 150:880–884, 2014 Hereditary angioedema – autosomal dominant; C’1 INH deficiency NEJM 359:1027–1036, 2008; J Allergy Clin Immunol 106:546–550, 2000; Lancet 356:213–217, 2000; NEJM 334:1666–1667, 1996; Medicine 71:206–215, 1992; Am J Med 35:37–44, 1963; Am J Med Si 95:362–367, 1888; type III - normal C1 INH activity in women with relationship to estrogenic activity JAAD 53:373–388, 2005; BJD 150:157–158, 2004; type III in men and women BJD 154:542–545, 2006; serpiginous erythema; triad of circumscribed edema of the skin, laryngeal edema, and abdominal pain BJD 161:1153–1158, 2009; Hosp TID No.40.1 rk 4:741–747, 1886; Monatsschr Prakt Dermatol 1:129–131, 1882; hereditary angioedema with normal C’1 INH in women JAAD 53:373–388, 2005 Hypocomplementemic vasculitis JAAD 48:311–340, 2003 Recurrent cutaneous necrotizing eosinophilic vasculitis AD 130:1159–66, 1994 Superior vena cava syndrome Urticarial vasculitis JAAD 49:S283–285, 2003; Clin Rev Allergy Immunol 23:201–216, 2002; JAAD 38:899–905, 1998; JAAD 38:899– 905, 1998; Medicine 74:24–41, 1995; JAAD 26:441–448, 1992

ANGIOKERATOMA CORPORIS DIFFUSUM BJD 149:405–409, 2003; JAAD 37:523–549, 1997 Acid sphingomyelinase deficiency Ped Derm 36:906–908, 2019

Angioedema with eosinophilia – transient variant BJD 144:169–174, 2001

Aspartylglycosaminuria (aspartylglycosaminidase) Paediatr Acta 36:179–189, 1991

Carcinoid syndrome AD 144:691–692, 2008; Allergol Immunopathol (Madrid) 32:235–237, 2004; Ann Int Med 123:636–637, 1995; Ann Surg 196:33=37, 1982

Beta mannosidase deficiency (beta-mannosidosis) BJD 152:177– 178, 2005

Familial Mediterranean fever Hypereosinophilic syndrome – red macules, red papules, plaques, and nodules, urticaria, angioedema Allergy 59:673–689, 2004; Am J Hematol 80:148–157, 2005; BJD 144:639, 2001; AD 132:535–541, 1996; Blood 83:2759–2779, 1994; AD 114:531–535, 1978; Medicine 54:1–27, 1975

TRAUMA Contact heat urticaria JAAD 53:373–388, 2005 Exercise-induced anaphylaxis, with or without food ingestion JAAD 55:290–301, 2006; JAAD 53:373–388, 2005; Sports Med 15:365– 373, 1993 Vibratory angioedema Dermatitis 20:346–347, 2009; BJD 156:1056–1058, 2007; JAAD 53:373–388, 2005; BJD 120:93–99, 1989; J Allergy Clin Immunol 71:546–551, 1983; Ann Int Med

Fabry’s disease - alpha galactosidase A deficiency NEJM 276:1163–1167, 1967 Fucosidosis type II (alpha-l-fucosidase) AD 107:754–757, 1973 Galactosialidosis – combined deficiency of beta-galactosidase and neuraminidase; due to defect of lysosomal protein (protective protein); conjunctival telangiectasia, telangiectasias of joints, Mongolian-like spots, café au lait macules, skin hyperextensibility, nevus of Ito BJD 149:405–409, 2003; AD 120:1344–1346, 1984 Galactosidosis type II Adult onset GM1 gangliosidosis (beta galactosidase) Clin Genet 17:21–26, 1980 Idiopathic (no enzyme deficiency) AD 123:1125–1127, 1987; JAAD 12:885–886, 1985) – telangiectasias or small angiokeratomas; and arteriovenous fistulae without metabolic disorders - papules AD 131:57–62, 1995 Kanzaki disease (Kanzaki-Schindler disease) (alpha-N-acetylgalactosidase) ( acetylgalactosaminidase) AD 129:460–465, 1993 Sialidosis type II BJD 152:177–178, 2005

ANNULAR LESIONS OF PENIS WITH SURFACE CHANGES 77

 NNULAR LESIONS OF PENIS A WITH SURFACE CHANGES

Bullous eruption in CREST syndrome, primary biliary cirrhosis and Sjogren’s syndrome JAAD 29:648–650, 1993

Bowenoid papulosis

Bullous pemphigoid erythema annulare centrifugum-like Acta Derm Croat 25:255–256, 2017; erythema gyratum repens Clin Exp Dermatol 77:401–406, 1982

Chancroid

Chronic granulomatous disease, neonatal AD 130:105–110, 1994

Erythema multiforme Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 65

Combined immunodeficiency syndrome - cutaneous granuloma JAAD 25:761–766, 1991

Erythroplasia of Queyrat Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 82

Common variable immunodeficiency – granulomatous dermatitis with annular atrophic scarred and scaly plaques J Clin Immunol 33:84–95, 2013; Dermatovenereol 18:107–113, 2010; J Clin Immunol 117:878–882, 2006; BJD 147:364–367, 2002; Mt Sinai Med J 68:326–330, 2001;

Factitial dermatitis Fixed drug eruptions Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 62 Herpes simplex virus infection, chronic Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p.16–17 Leishmaniasis BJD 139:111–113, 1998 Lichen planus – JAAD 79:789–804, 2018; JAAD 50:595–599, 2004; Cutis 51:116–118, 1993 Lichen sclerosus et atrophicus Linear IgA disease Lupus erythematosus, annular Mucha-Habermann syndrome Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p. 53 Necrobiosis lipoidica diabeticorum – chronic balanitis Dermatology 188:222–225, 1994 Nevus flammeus Non-venereal sclerosing lymphangitis Pityriasis rosea; JAAD 15:159–167, 1986 Porokeratosis BJD 144:643–644, 2001; Dermatology 196:256–259, 1998 Psoriasis Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p. 51 Reactive arthritis – circinate balanitis Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p. 52; Arthr Rheum 24:844– 849, 1981; Semin Arthritis Rheum 3:253–286, 1974 Seborrheic dermatitis Syphilis – primary - hard penile circumferential fold at coronal sulcus; secondary – annular syphilis JAAD 82:1–14, 2020 Tinea cruris (E. floccosum, T. rubrum) Tinea versicolor Trauma Warts (condylomata acuminata) Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p. 13 Zoon’s balanitis (plasma cell balanitis) Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p. 44

 NNULAR LESIONS WITH SURFACE A CHANGES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – paraphenylenediamine in hair dye – annular dermatitis of neck and back AD 148:1299–1301, 2012; allergic contact dermatitis to vanadium in titanium implant - widespread nummular plaques Cutis 99:245–249, 2017

Dermatitis herpetiformis – annular and rosette lesions Dermatomyositis – oval palatal erythematous patch in dermatomyositis with anti-TIF1gamma (p155) antibodies JAMA Derm 152:1049, 2016 Epidermolysis bullosa acquisita AD 133:1122–1126, 1997; annular bullae BJD 147:592–597, 2002 Graft vs. host disease – annular scaly papules of epithelioid granulomas BJD 149:898–899, 2003 IgA pemphigus with rosettes JAAD 25:383–386, 1991 IgA pemphigus (intraepidermal (subcorneal IgA pemphigus) - vesicles, pustules JAAD 82:1386–1392, 2020; BJD 171:650–656, 2014; Eur J Dermatol 11:41–44, 2001; JAAD 43:546–549, 2000; vesiculopustules JAAD 43:923–926, 2000; JAAD 32:352–357, 1995; JAAD 31:502–504, 1994; JAAD 24:993, 1992; intercellular IgA dermatosis resembling subcorneal pustular dermatosis AD 123:1062–1065, 1987 Intercellular IgA dermatosis of childhood AD 127:221–224, 1991 Interstitial granulomatous dermatitis with arthritis JAAD 34:957–961, 1996 Linear IgA disease (chronic bullous disease of childhood) – perioral, eyelids, ears, scalp, perineum, vulva; rosettes of bullae BJD 144:870–873, 2001; annular polycyclic bullae; palmar and plantar bullae in infancy; may have hemorrhagic bullae Ped Derm 15:108– 111, 1998; neonatal linear IgA disease Ped Derm 10:171–176, 1993; perfect annulus with peripheral bullae JAMA Derm 155:373– 374, 2019; annular psoriasiform, serpiginous red plaques of palms JAAD 51:S112–117, 2004; resembling erythema annulare centrifugum JAAD 51:S112–117, 2004 Lupus erythematosus – systemic lupus erythematosus – annular erythema Rook p. 2473, 1998, Sixth Edition; bullous or vesicular (annular bullae) JAAD 27:389–394, 1992; Arthritis Rheum 21:58– 61, 1978; discoid lupus erythematosus NEJM 269:1155–1161, 1963; neonatal – macular erythema or thin red plaque of forehead, periorbital, temples, upper cheeks, scalp, neck JAAD 40:675–681, 1999; Clin Exp Rheumatol 6:169–172, 1988; neonatal - annular scaling lesions with central atrophy of scalp and around ears Ped Derm 28:115–121, 2011; BJD 158:626–628, 2008; subacute cutaneous lupus erythematosus – annular, serpiginous, and polycyclic papulosquamous lesions Cutis 91:25–29, 2013; AD 148:190–193, 2012; BJD 156:1321–1327, 2007; Med Clin North Am 73:1073–1090, 1989; JAAD 19:1057–1062, 1988; Cutis 28:90–92, 1981; SCLE in children – annular and polycyclic Ped Derm 20:31–34, 2003; erythema gyratum repens Clin Exp Dermatol 77:129–134, 1982; systemic LE; arcuate scaly plantar plaques JAAD 49:S270–271, 2003 Morphea Pemphigoid gestationis (formerly herpes gestationes) – annular erythematous vesicular plaques Cutis 88:21–26, 2011; JAAD 40:847–849, 1999

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Pemphigus foliaceus, pemphigus herpetiformis variant AD 129:6973, 1993; pemphigus foliaceus of children – arcuate, circinate, polycyclic lesions JAAD 46:419–422, 2002; Ped Derm 3:459–463, 1986; erythema annulare centrifugum-like lesions BJD 171:1558– 1559, 2014 Pemphigus herpetiformis – annular erythematous patches with hyperpigmentation with or without vesicles; annular arcuate red plaques with edematous borders with erosions and vesicles AD 148:531–536, 2012; rosette lesions Ped Derm 27:488–491, 2010 Pemphigus vulgaris; IgG/IgA pemphigus – herpetiform, targetoid lesions BJD 147:1012–1017, 2002 Rheumatoid neutrophilic dermatitis Cutis 60:203–205, 1997 Sjogren’s syndrome - annular erythema of Sjogren’s syndrome JAAD 42:1069–1073, 2000 X-linked hypogammaglobulinemia

2004; chlorthalidone - SCLE associated with Hygroton JAAD 18:38–42, 1988; anastrozole (aromatase inhibitor)-induced SCLE BJD 158:628–629, 2008; golimumab (anti-TNF antibody)-induced SCLE AD 148:1186–1190, 2012; bevacizumab – recombinant humanized antibody against endothelial growth factor; annular plaques of scalp (SCLE) J Drugs Dermatol 1:1052–1055, 2013; mitotane-induced SCLE JAMA Derm 152:109–111, 2016; tiotropium bromide AD 141:911–912, 2005; leflunomide, antihistamines, gold Cutis 76:189–192, 2005; capecitabine and 5-fluorouracil JAAD 59:S4–6, 2008; capecitabine AD 145:340–341, 2009; gemcitabine JAMA Derm 149:1071–1075, 2013; proton pump inhibitors BJD 170:342–345, 2014; pantoprazole JAMA 314:1740–1743, 2015 Penicillamine-induced elastosis perforans serpiginosa JAMA Derm 150:785–787, 2014 Penicillin-induced bullous pemphigoid mimicking erythema multiforme JAAD 18:345–349, 1988 Prilosec – mimicking SCLE

CONGENITAL Congenital constriction band of the trunk (variant of amniotic band syndrome) Ped Derm 14:470–472, 1997

DRUG-INDUCED Cholesterol lowering drug – annular granulomatous reaction Dermatol Clin 33:509–630, 2015 Clindamycin-induced acute generalized exanthematous pustulosis AD 142:1080–1081, 2006 Cyclophosphamide and doxorubicin – SCLE AD 146:1113–1116, 2010 Erlotinib – painful annular pustular eruption; targetoid lesions Cutis 88:281–283, 2012 Erythema annulare centrifugum – drug-induced; cimetidine, chloroquine, estrogens, hydroxychloroquine, penicillin, progestogens, salicylates

Ranitidine (Zantac) Quinidine - lichen planus-like eruption Scopolamine patch - allergic contact dermatitis JAAD 13:247–251, 1985 Terbinafine – drug-induced SCLE BJD 148:1056, 2003; JAAD 44:925–931, 2001; AD 137:1196–1198, 2001 Tetanus shot reaction - personal observation Vitamin K reaction Cutis 61:81–83, 1998

EXOGENOUS AGENTS Fixed food eruption - strawberries JAAD 35:638–639, 1996 Irritant contact dermatitis ECG electrode dermatitis (parachlorometaxylenol) JAAD 15:348– 350, 1986 Nail – in the eye NEJM 372:1945–1952, 2015 Paraffinoma – morphea-like reaction

Fixed drug eruption – multiple drugs; JAMA 312:2281–2282, 2014 personal observation G-CSF JAAD 34:455–459, 1996 Heparin (subcutaneous) allergy JAAD 21:703–707, 1989 Interferon – erythema gyratum repens due to pegylated interferon AD 148:1213–1214, 2012 Linear IgA disease, drug-induced – annular bullae; amiodarone, captopril, cefamandole, cyclosporin, diclofenac, euglucon, furosemide, interleukin, lithium, phenytoin, somatostatin, sulfa, vigabatrin, piroxicam, vancomycin Cutis 73:65–67, 2004; JAAD 45:691–696, 2001 Lupus erythematosus – subacute cutaneous LE – malar rash, bullous lesions, vasculitic lesions of legs, crusted and necrotic annular, polycyclic scaly lesions in a photodistribution including the legs – terbinafine, thiazides, piroxicam, D-penicillamine, sulfonylureas, procainamide, oxyprenelol, chrysotherapy, griseofulvin, naproxen, spironolactone, diltiazem, cinnarizine, captopril, cilazapril, verapamil, nifedipine, interferon beta, ranitidine, infliximab, etanercept Cutis 81:156–157, 2008; AD 139:45–49, 2003; Lancet 359:579–580, 2002; JAAD 44:925–931, 2001; Ann Int Med 103:49–51, 1985; anti-tumor necrosis factor inhibitors JAAD 61:486–504, 2009; Mayo Clin Proc 84:979–984, 2009; adalimumabinduced SCLE Ped Derm 2015; Apr 6; JAAD 56:S114–116, 2007; etanercept-­induced SCLE Rheumatology (Oxford)40:1317–1319, 2000; infliximab-induced SCLE Clin Exp Dermatol 29:150–153,

INFECTIONS AND INFESTATIONS Anthrax - rosette of blisters surrounding central eschar Clin Inf Dis 19:1009–1014, 1994 Bejel (endemic syphilis) – annular lesions of trunk and extremities Campylobacter – red, annular, and serpiginous plaques of lower leg in HIV+ patient AD 142:1240–1241, 2006 Candida - chronic mucocutaneous candidiasis – tinea corporis- like changes Ann Rev Med 32:491–497, 1981 Chromomycosis AD 131:399–401, 1995 Cutaneous larva migrans Dermatophilus congolensis – due to contact with infected animals BJD 145:170–171, 2001 Erythrasma – disciform erythrasma Herpes simplex, chronic Am J Med 80:486–490, 1986 Impetigo – bullous (Staphylococcal) and Streptococcal Insect bites Leishmaniasis - chronic lupoid leishmaniasis AD 132:198–202, 1996; post-kala azar dermal leishmaniasis Acta DV 78:353–354, 1998; leishmaniasis recidivans – circinate papules at periphery of old scars Clin Inf Dis 33:1076–1079, 2001; JAAD 34:257–72, 1996 Leprosy – tuberculoid; borderline JAAD 68:879–881, 2013

Annular Lesions with Surface Changes Lobomycosis Lyme disease - erythema (chronicum) migrans – Borrelia burgdorferi JAAD 64:619–636, 2011; Am J Med 99:412–419, 1995 Mucormycosis - primary cutaneous JAAD 24:882–885, 1991 Mycobacterium africanum (tuberculosis) Clin Inf Dis 21:653–655, 1995 Mycobacterium haemophilum BJD 149:200–202, 2003 Mycobacterium tuberculosis - lupus vulgaris Dermatol Clin 33:541–562, 2015; lichen scrofulosorum – yellow to red-brown flat-topped papules, slightly scaly, surmounted with minute pustule; trunk AD 124:1421–1426, 1988; lupus vulgaris AD 126:1227, 1990; erythema induratum; pulmonary tuberculosis – erythema gyratum repens BJD 98:465–468, 1975; tuberculosis verrucosa cutis Ped Derm 33:264–274, 2016; Cutis 78:309–316, 2006; hematogenous disseminated tuberculosis – annular verrucous plaques of buttocks, scrotal ulcers, hyperkeratotic plaques of sole Clin Inf Dis 49:1402– 1404,1450–1451, 2009 Parvovirus B19 – subacute cutaneous lupus-like annular scaling erythematous rash Hum Pathol 31:488–497, 2000 Phaeohyphomycosis (Exserohilum rostratum) - porokeratosis-like JAAD 28:340–344, 1993

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Trypanosomiasis (African trypanosomiasis) AD 131:1178–1182, 1995 Vaccinia – generalized vaccinia Cutis 73:115–122, 2004 Warts - giant disseminated verrucosis (HPV2) (giant annular warts of trunk and verrucous claw hands and feet) associated with idiopathic CD4 lymphopenia AD 146:69–73, 2010 Yaws – secondary yaws Ped Derm 27:364–367, 2010; Cutis 85:85–89, 2010; ulcerated primary stage (mother yaw) – ulcerated nodule of glans

INFILTRATIVE LESIONS Alopecia mucinosa (follicular mucinosis) in children – annular hypopigmented plaque with raised annular border ; Ped Derm 30:192–198, 2013; in adults Dermatology 197:178–180, 2018; BJD 163:420–423, 2010; JAAD 10:760–768, 1984; AD 76:419–426, 1957 Erdheim-Chester disease, pediatric - facial plaques, psoriasiform plaques, papulosquamous lesions, annular lesions, central atrophic scarring; osteolysis and osteosclerosis BJD 178:261–264, 2018 Lichen amyloidosis

Pinta Scabies – annular patches Ped Derm 31:408–409, 2014 Sporotrichosis – annular crusted plaques of forearm and hand NEJM 380:771, 2019; fixed cutaneous JAAD 12:1007–1012, 1985 "Spotless" Rocky Mountain Spotted Fever - erythema migrans - like skin lesion Clin Inf Dis 21:1328–1329, 1995

INFLAMMATORY DISEASES Crohn’s disease - annular vegetative perianal plaque JAAD 63:165–166, 2010 Eosinophilic pustular folliculitis JAAD 55:285–289, 2006;

Syncephalastrum infection – annular lesion with scale in neonate Ped Derm 31:267–270, 2014

BJD 145:514–515, 2001; AD 132:341–346, 1996; JAAD 14:469– 474, 1986; annular plaque with pustules JAAD 51:S71–73, 2004

Syphilis - congenital -targetoid erythema multiforme-like lesions scalp JAAD 82:1–14, 2020; NEJM 371:2017, 2014; JAAD 55:S11– 15, 2006; BJD 149:658–660, 2003; Genitourin Med 68:195–196, 1992; secondary syphilis mimicking tinea imbricata JAAD 61:165– 167, 2009; secondary and tertiary Cutis 59:135–137, 1997; nodular tertiary syphilis – circinate and annular lesions JAAD 42:378–380, 2000; annular verrucous perianal dermatitis in secondary syphilis BJD 152:1343–1345, 2005;

Erythema multiforme Medicine 68:133–140, 1989; JAAD 8:763– 765, 1983

Tinea corporis – Trichophyton rubrum, T. megninii, E.floccosum; Trichophyton verrucosum – extensive annular lesions of trunk and neck JAMA 315:508–509, 2016; AD 94:35–37, 1966; tinea corporis, pedis - bullous or scaly; Majocchi’s granuloma - personal observation; Trichophyton mentagrophytes – annular bullae JAAD 55:153– 154, 2006; Nature Genet 17:241–244, 1997; tinea capitis; tinea faciei AD 114:250–252, 1978; tinea cruris The Clinical Management of Itching; Parthenon Publishing, 2000; p. xi; Trichophyton rubrum, invasive; radiation port dermatophytosis JAAD 19:1053–1056, 1988; dermatophyte immune restoration inflammatory syndrome (IRIS) Clin Inf Dis 40:113, 182–183, 2005 Tinea imbricata- Trichophyton concentricum – extensive involvement with pruritus and lichenification Curr Ped Rev 15:170–174, 2019; Cutis 83:186–191, 2009; Clin Exp Dermatol 13:232–233, 1988; Trans R Soc Trop Med Hyg 78:246–251, 1984

Post-inflammatory elastolysis and cutis laxa (PECL) in children – severe variant of anetoderma in black girls; begins as indurated annular plaque with collarette of scale; progress to finely wrinkled skin JAAD 51:165–185, 2004; JAAD 22:40–48, 1990; S Afr Med J 40:1016–1022, 1966 Reactive granulomatous dermatitis Dermatol Clin 33:509–630, 2015 Sarcoid Dermatol Clin 33:509–630, 2015; AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; Clinics in Chest Medicine 18:663– 679, 1997; necrotizing sarcoidal granulomatosis Cutis 80:313–316, 2007; atrophic sarcoid - annular plaques with cigarette paper wrinkling SkinMed 8:59–60, 2010; AD 122:320–322, 1986; Acta DV 57:367–379, 1977; BJD 83:255–262, 1970; annular plaques with peripheral hyperpigmentation of scalp The Dermatologist, January 2016, pp.47–48, 50

METABOLIC DISEASES Cystic fibrosis - scaly annular plaques AD 128:1358–1364, 1992; polycyclic psoriasiform dermatitis, resembling necrolytic migratory erythema JAAD 58:S29–30, 2008

Tinea versicolor - tinea versicolor with EAC-like lesions AD 120:380–382, 1984

Hereditary LDH-M subunit deficiency JAAD 24:339–342, 1991; AD 122:1420–1424, 1986; with acroerythema JAAD 27:262–263, 1992

Trichophyton mentagrophytes – tinea manuum; African pygmy hedgehog Cutis 105:314–316, 2020

Necrobiosis lipoidica diabeticorum Int J Derm 33:605–617, 1994; JAAD 18:530–537, 1988; NLD with perforating elastosis Cutis 57:326–328, 1996

Trichophyton tonsurans – tinea incognito; red plaque of face Cutis 102:370–372, 2018 Trichosporon – hyperpigmented and red annular plaque with surface change JAMA Derm 151:1139–1141, 2015

Necrolytic migratory erythema – recurrent seborrheic, serpiginous, annular papulosquamous eruptions; glucagonoma, chronic liver disease, inflammatory bowel disease, heroin abuse, pancreatitis,

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malabsorption syndromes JAMA Derm 155:1180, 2019; Int J Dermatol 49:24–29, 2010; J Eur Acad Dermatol 18:591–595, 2004 Necrotizing infundibular crystalline folliculitis – follicular papules with waxy keratotic plugs BJD 145:165–168, 2001 Phrynoderma – phrynoderma as sign of general malnutrition not specific for Vitamins A, B, E or essential fatty acid deficiency Ped Derm 22:60–63, 2005 Prolidase deficiency AD 127:124–125, 1991 Pseudoglucagonoma syndrome - with alcoholic liver disease AD 138:405–410, 2002; due to malnutrition AD 141:914–916, 2005; with chronic liver disease, chronic pancreatitis, traumatic necrotizing pancreatitis, celiac disease, jejunal adenocarcinoma AD 115:1429– 1432, 1979

NEOPLASTIC DISEASES Basal cell carcinoma Bowen’s disease - personal observation Desmoplastic trichoepithelioma AD 132:1239–1244, 1996 Extramammary Paget’s disease JAAD 17:910–913, 1987 Kaposi’s sarcoma Keloid Keratoacanthoma - resolving keratoacanthoma; multiple KAs on DLE JAAD 21:805–810, 1989; keratoacanthoma centrifugum JAAD 48:282–285, 2003 Keratoacanthoma centrifugum marginatum Cutis 73:257–262, 2004; JAAD 30:1–19, 1994; AD 111:1024–1026, 1975; Hautarzt 13:348– 352, 1962 Large cell acanthomas AD 123:1071–1076, 1987; JAAD 8:840–845, 1983 Lentigo Leukemia – HTLV-1 leukemia/lymphoma - personal observation Lichen planus-like keratosis - personal observation Lymphocytoma cutis Lymphoma - cutaneous T-cell lymphoma Practical Dermatol pp.34–38, March 2010; CTCL with malignancy of FOXP3 regulatory cells – red arciform and annular patches JAAD 61:348–355, 2009; CD8+ cytotoxic cutaneous T-cell lymphoma NEJM 357:2496–2505, 2007; hyperpigmented patches JAAD 60:359–375, 2009; CTCL mimicking EAC in a child BJD 152:565–566, 2005; CTCL mimicking porokeratosis of Mibelli JAAD 29:1046–1048, 1993; JAAD 27:327–330, 1992; annular necrosis with gamma/delta T cell lymphoma JAAD 26:865–870, 1992; Woringer-Kolopp disease (pagetoid reticulosis) – annular hyperkeratotic plaque JAAD 14:898–901, 1986; of hands and feet BJD 163:651–653, 2010; CTCL mimicking annular and gyrate erythema JAAD 47:914–918, 2002; primary cutaneous anaplastic large cell lymphoma AD 143:255–260, 2007; CD30+ anaplastic lymphoma BJD 159:240–242, 2008; adult T-cell leukemia/lymphoma with granuloma annulare-like lesions JAAD 60:848–852, 2009; subcutaneous panniculitis-like B-cell lymphoma Medallion-like dermal dendrocyte hamartoma – dumb-bell shaped atrophic hyperpigmented plaque of chest surface JAAD 59:169– 171, 2008; yellow-brown, blue-brown annular or oval depression of back of neonate; wrinkled surface, telangiectasias; thin hair on AD 142:921–926, 2006 Melanoma; Semin Oncol 2:5–118, 1975 Meyerson’s nevus – dermatitic halos surrounding melanocytic nevi, atypical nevi, seborrheic keratoses, stucco keratoses, keloids, benign lentigo, insect bite, basal cell carcinoma, squamous cell carcinoma, dermatofibroma, pityriasis rosea AD 139:1209–1214, 2003

Papular epidermal nevus with skyline basal cell layer (PENS) – flat topped hyperkeratotic papules, some annular Ped Derm 33:296– 300, 2016; JAAD 64:888–892, 2011 Porokeratosis - of Mibelli; pink-white plaque; autosomal dominant Cutis 79:22,53–54, 2007; JAAD 52:553–555, 2005; Cutis 72:391– 393, 2003; Curr Prob Derm 14:71–116, 2002; AD 122:586–587, 589–590, 1986; Gior Ital d Mal Ven 28:313–355, 1893;perioral erythematous plaque JAMA Derm 151:85–86, 2015 loss of distal phalanges (mutilation) Cutis 86:77–80, 2010; giant porokeratosis Hautarzt 41:633–635, 1990; hyperkeratotic porokeratosis Int J Dermatol 32:902–903, 1993; linear Ped Derm 21:682–683, 2004; Cutis 44:216–219, 1989; Int J Dermatol 27:589–590, 1988; disseminated superficial (actinic) porokeratosis – autosomal dominant Curr Prob Derm 14:71–116, 2002; Int J Dermatol 34:71–72, 1998; BJD 123:249–254, 1996; Cutis 42:345–348, 1988; palmoplantar porokeratosis JAAD 21:415–418, 1989; genital porokeratosis AD 145:715–720, 2009; at site of ionizing radiation for prostate cancer AD 146:1318–1320, 2010; disseminated superficial porokeratosis – annular keratotic facial papules BJD 171:427–429, 2014; porokeratosis palmaris et plantaris disseminata JAAD 21:415–418, 1989; porokeratosis ptychotropica – verrucous annular plaques of buttocks in butterfly distribution; Blaschko-esque, serpiginous, annular, hyperpigmented verrucous plaques of intertriginous areas and buttocks Ped Derm 37:248– 250, 2020; JAMA Derm 155:845, 2019; Australasian J Derm 58:e149–150, 2017; JAMA Derm 149:1099–1100, 2013; BJD 132:150–151, 1995 Seborrheic keratosis - personal observation Squamous cell carcinoma Stucco keratosis Woringer-Kolopp disease (pagetoid reticulosis) JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939

PARANEOPLASTIC DISEASES Erythema annulare centrifugum - leukemia – chronic lymphocytic leukemia BJD 157:1044–1045;1045–1047, 2007 Erythema gyratum repens - seen with malignancy, benign breast hypertrophy, CREST syndrome, ichthyosis, palmoplantar hyperkeratosis AD 111:227–229, 1975 Glucagonoma syndrome (necrolytic migratory erythema) JAAD 54:745–762, 2006; JAAD 24:473–477, 1991; JAAD 12:1032–1039, 1985; nummular dermatitis-like lesions Cutis 81:25,30–32, 2008 Interstitial granulomatous dermatitis, paraneoplastic (myeloma) JAMA Derm 151:1141–1142, 2015 Lupus erythematosus – paraneoplastic subacute cutaneous lupus erythematosus Cutis 91:25–29, 2013 Necrobiotic xanthogranuloma with paraproteinemia Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) - arciform and polycyclic lesions AD 137:193–206, 2001 Pityriasis rotunda Cutis 58:406–408, 1996; AD 119:607–6098, 1983 Porokeratosis of Mibelli BJD 156:1384–1385, 2007

PHOTODERMATOSES Actinic lichen planus AD 135:1543–1548, 1999 Annular elastolytic granuloma (actinic granuloma) – annular lesion with central wrinkling, atrophy, and white depigmentation JAMA Derm 152:1045–1046, 2016

Annular Lesions with Surface Changes

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Disseminated superficial actinic porokeratosis AD 146:1193–1194, 2010; JAAD 40:479–480, 1999; Int J Derm 38:204–206, 1999

upper arms, shoulders – seen in South African whites; precipitated by cold weather or fever BJD 98:491–495, 1978

Phototoxic dermatitis Polymorphic light eruption

Erythrokeratoderma variabilis (Mendes da Costa syndrome) – autosomal dominant – dark red fixed plaques with transient polycyclic red macules with fine scale JID 113:1119–1122, 1999; Ped Derm 12:351–354, 1995

PRIMARY CUTANEOUS DISEASES

Familial annular erythema – autosomal dominant; early infancy to puberty; vesiculation or scaling

Annular atrophic plaques of the face AD 100:703–716, 1969 Annular bullous congenital ichthyosiform erythroderma – annular desquamation; novel KRT10 mutation BJD 157:602–604, 2007 Annular epidermolytic ichthyosis BJD 141:642–646, 1999; JAAD 27:348–355, 1992 Annular erythema of infancy Annular lichenoid dermatitis of youth – annular lesion with scale with red palpable border and central hypopigmentation JAMA Derm 154:357–358, 2018; Ped Derm 24:582–584, 2007; JAAD 49:1029– 1036, 2003 Atrophia maculosa varioliformis cutis – linear, varioliform scars Ped Derm 18:230–233, 2001; JAAD 21:309, 1989; BJD 115:105–109, 1986 Atrophoderma of Pasini and Pierini JAAD 30:441–446, 1994 Circumscribed palmar or plantar hypokeratosis – red depressed or atrophic patch with ridged border JAAD 51:319–321, 2004; JAAD 49:1197–1198, 2003; JAAD 47:21–27, 2002 Confluent and reticulated papillomatosis Dyshidrosis Cutis 23:819–821, 1979 Elastosis perforans serpiginosa JAMA Derm 150:645–646, 2014; Ped Derm 23:219–224, 2006; AD 141:1457–1462, 2005; JAAD 51:1–21, 2004; AD 129:205–207, 1993; seen in Down’s syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, Rothmund-Thomson syndrome, acrogeria, Ehlers-Danlos type IV, scleroderma, penicillamine JAAD 46:161–183, 2002; elastosis perforans serpiginosa with pseudoxanthoma elasticum-like changes in Moya-Moya disease (bilateral stenosis and occlusion of basa intracranial vessels and carotid arteries) BJD 153:431–434, 2005 Epidermolysis bullosa simplex – migratory circinate erythema Ped Derm 37:358–361, 2020 Eosinophilic annular erythema Ped Derm 35:e255–256, 2018; Int J Dermatol 54:e96–98, 2015 Eosinophilic pustular folliculitis of Ofuji – circinate and serpiginous plaques with overlying papules and pustules in seborrheic areas; pustules are follicular JAAD 51:571–573, 2004; J Dermatol 16:388–391, 1989; Hautarzt 39:527–530, 1988; Acta DV 50:195– 203, 1970; red plaque with pustules JAAD 46:827–833, 2002 Epidermolysis bullosa simplex, dystrophica; epidermolysis bullosa herpetiformis (Dowling-Meara) JAAD 28:859–861, 1993; epidermolysis bullosa S/P ECG Epidermolytic hyperkeratosis – annular and polycyclic plaques JAAD 27:348–355, 1992 Erythema annulare centrifugum Ped Derm 33:501–506 2016; BJD 160:119–126, 2009; Ann Dermatol Syphil 6:57–76, 1916 Erythema dyschromicum perstans JAAD 21:438–442, 1989 Erythema elevatum diutinum BJD 67:121–145, 1955 Erythema papulosa semicircularis recidivans Dermatitis 23:44–47, 2012 Erythrokeratoderma hiemalis (erythrokeratolysis hiemalis (Oudtshoorn disease)) – palmoplantar erythema, cyclical and centrifugal peeling of affected sites, targetoid lesions of the hands and feet; annular serpiginous lesions of lower legs, knees, thighs,

Figurate erythemas  Erythema annulare centrifugum Ped Derm 33:501–506 2016; BJD 160:119–126, 2009; Ann Dermatol Syphilol 6:57–76, 1916; Am J Dermatopathol 25:451–462, 2003in infancy JAAD 14:339– 343, 1986   Associations with erythema annulare centrifugum   Acute myeloblastic leukemia Ann Dermatol Venereol 116:6–7, 1989   AIDS   Alendronate JAAD 48:945–946, 2003   Ampicillin J Indian Med Assoc 65:307–308, 1975   Ascariasis AD 117:582–585, 1981   Blood dyscrasia Arch Klin Exp Dermatol 195:434–446, 1953   Breast cancer Cutis 26:282–284, 1980   Breast hypertrophy, erythema annulare centrifugum, generalized melanoderma, verrucae vulgaris and SLE Acta DV (Stockh) 52:33, 1972   Bullous pemphigoid Br J Dermatol 110:378–379, 1984   Candida Hautarzt 236:466–470, 1975   Carcinoid tumor NtJ Frtmsyol 94:452–456, 2976    Cat scratch disease Int J Derm 17:656–658, 1988   Chloroquine AD 95:37–39, 1967   Chronic polyarthritis J Rheumatol 38:59–66, 1979   Cimetidine Br Med J [Clin Res Ed] 283:698, 1981   Dysproteinemia Br J Dermatol 85:546–560, 1971   Epstein-Barr virus Acta Paediatr Scand 63:788–792, 1974   Familial Cutis 44:139–170, 1989   Gold thiomalate therapy JAAD 25:557–560, 1991; JAAD 27:284–287, 1992   Graves’ disease AD 118:623, 1982   Hodgkin’s diseases Int J Dermatol 32:59–61, 1993   Hydrochlorothiazide Int J Dermatol 27:129–130, 1988   Hydroxychloroquine sulfate Cutis 36:129–30, 1985    Hypereosinophilic syndrome Med Cutan Ibero Lat Am 16:299–304, 1988; Cutis 35:53–55, 1985   Congenital ichthyosis Dermatologica 140:75, 1970   Infectious mononucleosis    Ingested fungus (cheese) AD 90:54–58, 1964   Inflammatory carcinoma (carcinoma erysipelatoides) Acta Derm Venereol (Stockh) 73:138–140, 1993   Internal malignancy AD 87:246–251, 1963   Leukemia – chronic lymphocytic leukemia BJD 157:1044– 1045;1045–1047, 2007   Liver disease AD 122:1239–1270, 1986   Lyme disease Dermatol Clin 3:129–139, 1985   Malignant histiocytosis Clin Exp Dermatol 9:608–613, 1984   Molluscum contagiosum AD 114:1853, 1978   Phenothiazine Hautarzt 41:161–163, 1990    Phthirus pubis infestation BJD 149:1291, 2003   Piroxicam JAAD 13:840–841, 1985   Polycythemia vera Ann Dermatol Venereol 111:767–768, 1984    Prostate adenocarcinoma Ann Dermatol Venereol 106:789–92, 1979   Psoriasis Hautarzt 38:509–520, 1987   Sarcoidosis Br J Dermatol 1060:713–716, 1982   Sjogren’s syndrome and systemic lupus erythematosus JAAD 25:557–560, 1991

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  Spironolactone Ann DV 114:375–376, 1987   Terbinafine AD 131:960–961, 1995   Thiacetazone Australas J Dermatol 28:44, 1987    Tinea pedis Arch Dermatol Syphilol 70;355–359, 1954   Tuberculosis Int J Dermatol 21:538–539, 1982    Urinary tract infection Hautarzt 30:673–675, 1979  Annular recurring erythema annularis centrifugum – spring and summer JAAD 54:1091–1095, 2006   Erythema chronicum migrans   Erythema gyratum atrophicans  Erythema gyratum perstans  Erythema gyratum repens  Erythema marginatum – rheumatic fever JAAD 8:724–728, 1983; Ann Int Med 11:2223–2272, 1937–1938   Familial annular erythema  Glucagonoma  Infantile epidermolytic erythema gyratum AD 120:1601–1603, 1984   Keratolytic winter erythema   Persistent annular erythema of infancy Ped Derm 10:46–48, 1993   Pityriasis rubra pilaris   Psoriasis    Subacute cutaneous lupus erythematosus    Tinea corporis    Tinea imbricata

Parakeratosis variegata

Geographic tongue (benign migratory glossitis) J Am Dent Assoc 115:421–424, 1987

Progressive symmetric erythrokeratoderma

Granuloma annulare, disseminated - personal observation

Psoriasis – recurrent circinate erythematous psoriasis of Bloch and Lapiere; annular plaque type psoriasis Ped Derm 22:15–18, 2005; annular pustular psoriasis Ped Derm 19:19–25, 2002; JAAD 24:186–194, 1991; Cutis 45:439–442, 1990; AD 108:687–688, 1973; psoriasis mimicking porokeratosis

Granuloma multiforme Int J Dermatol 4:441–443, 2004 Hailey-Hailey disease – arciform and circinate plaques Australas J Dermatol 37:196–198, 1996; BJD 126:275–282, 1992; Arch Dermatol Syphilol 39:679–685, 1939 Ichthyosis bullosa of Siemens – mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray rippled hyperkeratosis of extremities, lower trunk, flexures; hypertrichosis; circumscribed patchy scaling (mauserung); palmoplantar blistering with hyperhidrosis BJD 140:689–695, 1999; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986 Juvenile circumscribed pityriasis rubra pilaris Ped Derm 25:125– 126, 2008 Keratolysis exfoliativa - personal observation Keratosis follicularis squamosa – follicular hyperkeratotic papule; annular with scale BJD 144:1070–1072, 2001 Lichen planus  Annular atrophic lichen planus AD 141:93–98, 2005; JAAD 25:392–394, 1991; of breasts JAMA Derm 155:1187–1188, 2019  Annular JAAD 50:595–599, 2004; J Dermatol 19:414–419, 1992; J Cutan Dis 37:639–670, 1919 Hypertrophic  Lichen planus atrophicus annularis (actinic lichen planus) Ped Derm 34:713–714, 2017; JAAD 25:392–394, 1991   Lichen planus pigmentosus - personal observation Lichen sclerosus et atrophicus – wrinkled lesions, atrophic vulvar with shrinkage Cutis 67:249–250, 2001; Trans St John’s Hosp Dermatol Soc 57:9–30, 1971 Lichen simplex chronicus Lichen striatus, annular BJD 101:351–352, 1979 Lipoatrophia semicircularis Miescher’s granuloma Nummular dermatitis Ped Derm 35:611–615, 2018; BJD 95:653– 656, 1976

Parapsoriasis en plaque (large plaque parapsoriasis) – personal observation Perforating granuloma annulare JAAD 3:217–230, 1980 Perifollicular macular atrophy (perifollicular elastolysis) – gray-white finely wrinkled round areas of atrophy with central hair follicle BJD 83:143–150, 1970 Peristomal irritant contact dermatitis – annular scaling dermatitis BJD 166:103–109, 2012 Pityriasis alba Pityriasis lichenoides chronica Pityriasis rosea JAAD 15:159–167, 1986; pityriasis rosea with erythema multiforme-like lesions JAAD 17:135–136, 1987 Pityriasis rotunda – large annular hyperpigmented scaly patches; mutation in profilaggrin N-terminal domain BJD 166:227–229, 2012; may be paraneoplastic phenomenon; or with leprosy AD 144:1509– 1514, 2008; Ped Derm 19:200–203, 2002; JAAD 31:866–871, 1994; JAAD 14:74–78, 1986; BJD 76:223–227, 1964; familial pityriasis rotunda BJD 156:1365–1367, 2007 Pityriasis rubra pilaris – erythema gyratum repens JAAD 37:811– 815, 1997 Poikiloderma vasculare atrophicans with or without CTCL Pseudo-ainhum

Recurrent erythema annulare BJD 135:972–975, 1996; Ann DV 192:457, 2002 Seborrheic dermatitis petalloid - personal observation Subcorneal pustular dermatosis of Sneddon-Wilkinson – pustules which expand to annular and serpiginous lesions with scaly edge; heal with hyperpigmentation BJD 176:1341–1344, 2017; Ped Derm 20:57–59, 2003; BJD 145:852–854, 2001; J Dermatol 27:669–672, 2000; Cutis 61:203–208, 1998; JAAD 19:854–858, 1988; BJD 68:385–394, 1956 Symmetric progressive erythrokeratoderma Transient acantholytic dermatosis (Grover’s disease) - nummular plaques with scale/crust JAAD 35:653–666, 1996 Vitiligo - inflammatory vitiligo with figurate papulosquamous lesions Dermatology 200:270–274, 2000

PSYCHOCUTANEOUS DISEASE Factitial dermatitis

SYNDROMES Acquired progressive kinking of the hair Ped Derm 21:265–268, 2004 Acrogeria – elastosis perforans serpiginosa Annular epidermolytic ichthyosis – variant of bullous congenital ichthyosiform erythroderma – mutation in keratin 10 JID 111:1220– 1223, 1998 Ataxia telangiectasia – facial granulomas BJD 153:194–199, 2005 Conradi-Hunermann-Happle syndrome – transient scaly plaques of limbs, trunk, and scalp; X-linked dominant (mosaic for emopamil-

Annular Lesions Without Surface Changes binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309–1313, 2012

Laser hair removal - personal observation

Down’s syndrome – elastosis perforans serpiginosa

Radiation dermatitis - chronic

Ehlers-Danlos syndrome, type IV – elastosis perforans serpiginosa JAMA Derm 153:595–596, 2017

Radiation-induced pemphigus foliaceus of the breast JAAD 54:S251–252, 2006

Genodermatosis en cocarde of Degos – autosomal dominant – large annular scaling plaques

Suction device trauma of newborn

Hereditary LDH M-subunit deficiency – annular red rash in summer, resolves in autumn; muscular symptoms; small papules and annular red centrifugal spread BJD 172:1674–1676, 2015; AD 122:1420– 1424, 1986

VASCULAR

Hypereosinophilic syndrome – multiple round and oval red patches of trunk; FIP1L1-PDGFRA fusion gene Brit Med J Case Rep Oct 15, 2019; BJD 157:1284–1287, 2007; annular scaly red plaque of necrotizing vasculitis associated with deep vein thrombosis AD 141:1051–1053, 2005 Ichthyosis exfoliativa - annular epidermal ichthyosis Kawasaki’s disease - macular, morbilliform, urticarial, scarlatiniform, erythema multiforme-like, pustular, erythema marginatum-like exanthems, annular lesions with peripheral pustules Cutis 72:354– 356, 2003; JAAD 39:383–398, 1998 KLICK syndrome (keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; Acta DV 77:225–227, 1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989 Lipoid proteinosis – early lesions BJD 148:180–182, 2003 Netherton’s syndrome - ichthyosis linearis circumflexa Ped Derm 25:253–254, 2008; BJD 131:615–621, 1994; AD 122:1420–1424, 1986; JAAD 13:329–337, 1985 Osteogenesis imperfecta - elastosis perforans serpiginosa Pseudoxanthoma elasticum - elastosis perforans serpiginosa Reactive arthritis – circinate balanitis Ped Derm 37:199–201, 2020; keratoderma blenorrhagicum; flexural confluent circinate lesions; Semin Arthritis Rheum 3:253–286, 1974 Reticular erythematous mucinosis syndrome (REM syndrome) Rothmund-Thomson syndrome – elastosis perforans serpiginosa Rowell’s syndrome JAAD 21:374–377, 1989 Sweet’s syndrome - pustules and/or pustular plaques Hautarzt 46:283–284, 1995; JAAD 16:458–462, 1987; AD 123:519–524, 1987; BJD 76:349–356, 1964; in infancy; Sweet’s syndrome in infancy with acquired cutis laxa Ped Derm 26:358–360, 2009 Wells’ syndrome - annular plaques with collarette of bullae BJD 143:425–427, 2000; AD 133:1579–1584, 1997

TOXINS Dioxin - erythema elevatum diutinum-like lesions of late dioxin exposure JAAD 19:812–819, 1988

TRAUMA Chilblains Childbirth - annular blisters due to vacuum extraction AD 135:697– 703, 1999 Cupping – annulus with bullae JAMA Derm 155:237, 2019

83

Lip licker’s dermatitis - personal observation

Granulomatosis with polyangiitis – ulcerated annular plaque of forehead Ped Derm 33:551–552, 2016 Leukocytoclastic vasculitis, including Henoch-Schonlein purpura Osler-Weber-Rendu disease Pigmented purpuric eruption (eczematoid) Pustular vasculitis – annular pustular plaques with central necrosis Spider telangiectasia Urticarial vasculitis

ANNULAR LESIONS WITHOUT SURFACE CHANGES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Autoimmune-related granulomatous dermatitis – confluent widespread red plaques; annular red plaques; autoimmune thyroid disease; autoimmune hepatitis Case Rep Dermatol Med 2013; Case Rep Dermatol 4:80–84, 2012 Autoimmune progesterone dermatitis JAAD 47:311–313, 2002 Bullous pemphigoid – figurate lesions; IgA anti-p200 pemphigoid (p200 is laminin gamma 1) – blisters with serpiginous urticarial and annular plaques AD 147:1306–1310, 2011 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis, epididymitis, cold-induced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, conjunctivitis Ped Derm 33:602–614, 2016 Chronic granulomatous disease - arcuate dermal erythema AD 113:798–800, 1977 Dermatitis herpetiformis Graft vs. host disease – chronic, sclerodermoid GVH with mucin BJD 142:529–532, 2000 Lupus erythematosus  Annular erythema of face with anti-Ro/SSA antibodies BJD 150:1005–1008, 2004  Lupus erythematosus gyratum repens – migratory gyrate annular erythema Clin Exp Dermatol 7:129, 1982  Neonatal – annular erythema without scale Cutis 80:278, 281–283, 2007; Japanese infants Medicine 63:362–378, 1984   Subacute cutaneous lupus erythermatosus (SCLE)  Anti-Ro/SSA associated recurrent annular erythema J Dermatol Sci 12:127–131, 1996  Tumid lupus – annular plaque without scale BJD 162:64–73, 2010; JAAD 48:901–908, 2003; Cutis 69:228–230, 2002; Am J Dermatopathol 21:356–360, 1999   Urticarial vasculitis - personal observation

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Morphea - personal observation Pemphigoid gestationes; JAAD 40:847–849, 1999 Rheumatoid arthritis - palisaded neutrophilic granulomatous dermatitis of rheumatoid arthritis (rheumatoid neutrophilic dermatosis) JAAD 47:251–257, 2002; AD 133:757–760, 1997; Cutis 60:203–205, 1997

Fixed drug reaction – round or oval edematous dusky red macules SKINmed 10:373–383, 2012; flat gray-brown patches due to Baczol Antigripal, Baczol Expectorante, Bactrizole Balsamico Forte Suspension (El Salvadoran OTC containing trimethoprim/sulfamethoxazole) MMWR 62:914–916, 2013 G-CSF JAAD 34:455–459, 1996

Serum sickness - personal observation

Heparin hypersensitivity reactions Thromb Haemost 96:611–617, 2006

Sjogren’s syndrome - annular purpura J Korean Med Sci 15:115– 118, 2000; annular erythema of forehead, temples, neck, and thigh Clin Exp Rheumatol 22:55–62, 2004; JAAD 20:596–601, 1989

Immune checkpoint inhibitors – granuloma annulare JAAD 81:1165–1175, 2019

Still’s disease, including adult Still’s disease erythema chronicum migrans-like lesion J Eur Acad Dermatol Venereol 19:360–363, 2005 Urticaria – acute or chronic

CONGENITAL LESIONS

Interferon alpha (pegylated) and ribavirin as treatment for hepatitis C infection – sarcoidosis AD 141:865–868, 2005 Interstitial granulomatous drug reaction – red to violaceous annular plaques in skin folds, medial arms; calcium channel blockers, ACE inhibitors, beta blockers, lipid lowering agents, antihistamines, anticonvulsants, antidepressants, diuretics, NSAIDS, sennoside, herbal medications Advances in Dermatol 22:31–53, 2007; JAAD 52:712–713, 2005; J Cutan Pathol 25:72–78, 1998

Annular erythema of infancy JAMA Derm 154:1213–1214, 2018; Ped Derm 34:101–102, 2017; JAMA Derm 150:565–566, 2014; Australas J Dermatol 43:55–61, 2002; Clin Exp Dermatol 25:404– 405, 2000; Ped Derm 10:46–48, 1993; AD 117:145–148, 1981;

Iohexol (intravenous contrast material) – annular plaque of breast J Drugs in Dermtol 10:802–804, 2011

Aplasia cutis congenita

Linear IgA disease, drug-induced – red annular plaques; amiodarone, captopril, cefamandole, cyclosporin, diclofenac, euglucon, furosemide, interleukin, lithium, phenytoin, somatostatin, sulfa, vigabatrin, piroxicam, vancomycin JAAD 45:691–696, 2001

Hair collar sign - as sign of spinal neural tube defects Ped Derm 24:138–140, 2007 Hair whorl – parietal scalp

Isotretinoin - acquired kinking of the hair Clin Exp Dermatol 15:14–145, 1990

Halo scalp ring – prolonged pressure on vertex by cervix AD 123:992–994, 1987

Morbilliform drug eruption with accentuation under cardiac leads

Medallion-like dendritic hamartoma - personal observation

Propranolol – annular telangiectatic perivascular angiomatosis – red to violaceous hyperpigmented annular plaques with central clearing and radial telangiectasia BJD 169:1369–1371, 2013

Meningocele (rudimentary meningocele; primary cutaneous meningioma) - annular tuft of hair over sequestrated meningocele Ped Derm 14:315–318, 1994; Ped Derm 15:388–389, 1998 Neonatal erythema of infancy – recurrent annular diffuse red plaques JAMA Derm 150:565–566, 2014; AD 117:145–148, 1981   Differential diagnosis:   Urticaria    Neonatal lupus erythematosus    Erythema gyratum atrophicans transient neonatale    Erythema annulare centrifugum    Familial annular erythema    Erythema gyratum perstans

Non-pigmenting fixed drug eruption JAAD 23:379–381, 1990

Prostaglandin E – in neonate; migratory polycyclic macular eruption Cases of the Year, Pre-AAD Pediatric Dermatology Meeting Ranitidine (Zantac) Sorafenib - erythema marginatum hemorrhagicum – annular scalloped hemorrhagic macules JAAD 64:1194–1196, 2011; annular leukocytoclastic vasculitis J Drugs in Dermatol 9:697–698, 2010 TNF alpha inhibitors - interstitial granulomatous dermatitis; annular papules with clear centers AD 142:198–202, 2006 Vitamin K injection allergy JAAD 27:105–106, 1992

Raised limb bands BJD 147:359–363, 2002

EXOGENEOUS AGENTS DRUG-INDUCED Acitretin – acquired kinking of hair J Drugs Dermatol 6:937–938, 2007

Exogenous ochronosis - annular granulomatous lesions Am J Dermatopathol 17:18–22, 1995 Eyebrow ring

Anakinra – interstitial granulomatous dermatitis; periaxillary annular red plaque JAAD 59:S25–27, 2008

Pili migrans Ped Derm 21:612–613, 2004

Anthralin - post-inflammatory hyperpigmentation after anthralin therapy

Tongue ring

Chlorthalidone - subacute cutaneous lupus erythematosus JAAD 18:38–42, 1988

Tattoo Zirconium granuloma

Corticosteroids, topical – tinea incognito

INFECTIONS AND INFESTATIONS

Docetaxel recall after docetaxel extravasation – annular serpiginous patch AD 146:1190–1191, 2010

Arcanobacterium haemolyticum - annular urticarial lesions JAAD 48:298–299, 2003

Drug rash, morbilliform, accentuated under cardiac leads

Aspergillus sepsis

Etretinate – acquired kinking of the hair Clin Exp Dermatol 10:426–431, 1985

Cutaneous Borreliosis – acrodermatitis chronica atrophicans, cutis laxa-like changes, red patches, erythema migrans, erythema and

Annular Lesions Without Surface Changes edema of foot, poikilodermatous changes, red macules and telangiectasias JAAD 72:683–689, 2015 Candida sepsis Cat scratch disease - erythema marginatum-like lesions, erythema multiforme-like lesions Derm Times pp.39–40, Aug 1997 Chromomycosis - multinodular annular brown plaque of thigh; Fonsecaea pedrosoi JAAD 63:1083–1087, 2010 Demodicidosis in childhood acute lymphocytic leukemia J Pediatr 127:751–754, 1995 Epstein-Barr virus infection, chronic (infectious mononucleosis) granuloma annulare-like eruption AD 124:250–255, 1988 Erysipelas Erysipeloid Clin Microbiol Rev 2:354–359, 1989 Fusarium roseum infection - granuloma annulare like lesion AD 123:167–168, 1987 Fusarium sepsis – annular lesions with or without central necrosis Hawaiian box jellyfish sting (Carybdea alata) JAAD 36:991–993, 1996 Herpes simplex - dystrophic calcinosis due to intrauterine herpes simplex infection Ped Derm 3:208–211, 1986

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  Anaplasma phagocytophilum   Babesia microti   Borrelia miyamotoi    Deer tick virus (Powassan virus)   Ehrlichia species Wisconsin Mycobacterium hemophilum JAAD 43:913–915, 2000 Mycobacterium tuberculosis - lupus vulgaris Medicine 60:95–109, 1980; M. africanum (M. tuberculosis complex) - circinate and annular facial plaques, around nose J Clin Inf Dis 21:653–655, 1995 Parvovirus B19 – papular purpuric gloves and socks syndrome; annular purpura of palms and feet JAAD 54:896–899, 2006 Rheumatic fever – erythema marginatum Trans St John’s Hsop Dermatol Soc 50:105–112, 1964 Rhizopus oryzae - personal observation Rickettsia slovaca (Hungary) – Dermacentor marginatus or D. reticulatus tick bite; erythema marginatum-like lesions; scalp papules, crusted scalp papules and subsequent alopecia; tick-borne lymphadenopathy Clin Inf Dis 34:1331–1336, 2002 Rocky Mountain spotted fever (spotless RMSF) - erythema migrans-like lesions J Clin Inf Dis 21:1328–1329, 1995 Scarlet fever – erythema marginatum

Human bite

Schistosoma mansoni BJD 103:205, 1980

Insect bite reaction

Southern tick-associated rash infection (erythema migrans-like illness) – Borrelia lonestari; targetoid erythema migrans lesions without evidence of Borrelia infection; reported from Georgia, Kentucky, Maryland, Missouri, North Carolina, and South Carolina JAAD 72:371–372, 2015; Clin Inf Dis 40:429, 475–476, 2005; J Clin Microbiol 42:1163–1169, 2004; JAAD 49:363–392, 2003; Emerg Inf Dis 7:471–473, 2001; AD 135:1317–1326, 1999; AD 134:955–960, 1998; Arch Int Med 157:2635–2641, 1997; J Inf Dis 172:470–480, 1995

JC virus annular erythema - personal observation Leishmaniasis recidivans – circinate papules at periphery of old scars Clin Inf Dis 33:1076–1079, 2001; JAAD 34:257–72, 1996; post-kala azar dermal leishmanoid - personal observation Leprosy (Mycobacterium leprae) - macular lepromatous leprosy AD 113:1027–1032, 1997; tuberculoid leprosy - annular pink plaque of temple JAAD 60:1018–1021, 2009; JAAD 57:914–917, 2007; borderline leprosy – annular, linear, and serpiginous plaques Clin Inf Dis 68:1241–1243, 2019; JAMA Derm 154:1076–1077, 2018; targetoid and annular lesions Cutis 92:187–189, 2013; NEJM 364:1657, 2011; borderline lupus vulgaris; id reaction to Mycobacterium leprae Cutis 54:282–286, 1994; type 1 leprosy reaction JAMA Derm 149:74–78, 2013; reversal reaction JAAD 20:857–860, 1989; lepromatous phlebitis of external jugular vein (post-auricular red annular plaque) JAAD 49:1180–1182, 2003; trichophytid leprosy – annular lesion with raised edges and central healing JAAD 54:559–578, 2006; lepromatous leprosy Clin Inf Dis 52:1342, 1388–1389, 2011 Lyme disease - erythema migrans; annular red plaque NEJM 370:1724–1731, 2014; BJD 171:528–543, 2014; JAAD 64:619–636, 2011; JAAD 49:363–392, 2003;Clin Inf Dis 31:533–542, 2000; NEJM 321:586–596, 1989; AD 120:1017–1021, 1984; Science 216:1317–1319, 1982; acrodermatitis chronica atrophicans – Borrelia afzelii; annular erythematous slightly atrophic patches of ankles and feet Clin Inf Dis 57:1751,1782–1783, 2013 Differential diagnosis of Lyme disease NEJM 370:1724–1731, 2014   Cellulitis   Erythema multiforme   Granuloma annulare    Hypersensitivity to insect bite   Insect bite   Nummular dermatitis   Spider bite   Tinea   Urticaria    Wells’ syndrome   Coinfections with Lyme disease NEJM 370:1724–1731, 2014

Sporotrichosis, fixed cutaneous JAAD 12:1007–1012, 1985 Stingray bite Cutis 58:208–210, 1996 Syphilis - primary – hard penile circumferential fold JAAD 82:1–14, 2020; JAAD 26:700–703, 1992; secondary – discoid, annular, circinate papules and plaques AD 147:869–870, 2011; secondary syphilis mimicking tinea imbricate (atypical annular morphology) Clin Inf Dis 51:929–930,980–982, 2010; JAAD 61:165–167, 2009; nodular tertiary lesions mimicking granuloma annulare JAAD 42:378–380, 2000 Tick bite - personal observation Tinea corporis, pedis, manuum, faciei – steroid modified tinea – concentric rings of erythema or plaques Int J Dermatol 22:39–42, 1983 Trypanosomiasis (Trypanosomiasis brucei rhodesiense (African trypanosomiasis)) – edema of face, hands, feet with transient red macular, morbilliform, petechial or urticarial dermatitis; circinate, annular of trunk annular red patch of thigh NEJM 342:1254, 2000 Verrucae - flat warts Viral exanthem Wasp sting - personal observation

INFILTRATIVE DISEASES Acral persistent papular mucinosis JAAD 21:293–297, 1989 Jessner’s lymphocytic infiltrate – annular, arciform lesions JAAD 58: 217–223, 2008; BJD 157:402–403, 2007; AD 125:1525–1530, 1989 Lymphocytoma cutis (pseudolymphoma) - personal observation Urticaria pigmentosa

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INFLAMMATORY DISEASES Annular atrophic connective tissue panniculitis – erythematous nodules and plaques of ankles followed by circumferential band of atrophy Ped Derm 28:146–148, 2011; Ped Derm 28:142–145, 2011; J Cut Pathol 38:270–274, 2011; AD 146:877–881, 2010 Eosinophilic pustular folliculitis (plaque-type) JAAD 14:469–474, 1986; Ofuji’s disease – giant annular erythematous plaques of face, chest, and back Cutis 86:190–194, 2010 Erythema multiforme Medicine 68:133–140, 1989; JAAD 8:763– 765, 1983

Subacute migratory nodular panniculitis (Villanova) (erythema nodosum migrans) – red leg plaque AD 128:1643–1648, 1992; Cutis 54:383–385, 1994; Acta DV (Stockh) 53:313–317, 1973; AD 89:170–179, 1964 Urticaria-like neutrophilic dermatosis - annular urticarial plaques without scale – IgA gammopathy BJD 170:1189–1191, 2014; Medicine (Balt)88:23–31, 2009 Urticaria multiforme – wheals, fever, arcuate, annular, polycyclic lesions; ecchymotic (dusky) center or central pallor; edema of hands and feet; aged 4 months to 4 years Cutis 89:260:262–264, 2012; Ped Derm 28:436–438, 2011; Pediatrics 119:e1177–1183, 2007

Erythema nodosum Goodpasture’s syndrome - annular erythematous macule AD 121:1442–1444, 1982

METABOLIC DISEASES

Inflammatory bowel disease – cutaneous granulomata

Arcus (annulus) senilis (atherosclerosis)

Interstitial granulomatous dermatitis – annular plaques, linear erythematous cords BJD 152:814–816, 2005; JAAD 47:251–257, 2002; JAAD 46:892–899, 2002; JAAD 45:286–291, 2001; pink annular plaque JAAD 58:S100–102, 2008; interstitial granulomatous dermatitis with arthritis JAAD 34;957–961, 1996; giant annulus JAAD 55:S32–37, 2006; annular polycyclic hyperpigmented plaques associated with coccidioidomycosis BJD 174:881–884, 2016 ­  Associated medications:   ACE inhibitors  Adalimumab  Anticonvulsants  Antidepressants  Antihistamines   Calcium channel blockers  Diuretics  Etanercept  Ganciclovir   Herbal medications  Infliximab   Lipid lowering agents  Sennoside

Calcinosis cutis due to EEG paste – annular forehead plaque AD 138:405–410, 2002

Kawasaki’s disease – polycyclic figurate erythema Ped Derm 30:491–492, 2013

Atrial myxoma – violaceous, annular and serpiginous lesions Cutis 62:275–280, 1998; JAAD 21:1080–1084, 1989; JAAD 32:881–883, 1995

Lipoatrophic panniculitis (lipophagic panniculitis of childhood; annular atrophy of the ankles) – red nodules and red plaques of extremities; annular atrophy of ankle and/or dorsal foot AD 146:877–881, 2010 Neutrophilic eccrine hidradenitis Ann DV 119:605–611, 1992; AD 118:263–266, 1982; large annuli of breasts BJD 151:507–508, 2004 Neutrophilic sebaceous adenitis – annular erythematous indurated plaques of face and chest in photodistribution; persistent malar erythema with atrophy; JAMA Derm 154:1215–1216, 2018; JAAD 36:845–846, 1997; AD 129:910–911, 1993; JAAD 60:887–888, 2009; annular expanding red plaques of face and back with fever, lymphadenopathy JAMADerm 150:1225–1226, 2014; AD 129:910– 911, 1993 Palisaded neutrophilic and granulomatous dermatitis – annular papules and plaques Ped Derm 36:156–157, 2019; BJD 159:488– 489, 2008 Relapsing polychondritis – papular and annular fixed urticarial eruption; associated with myelodysplasia JAAD 65:1161–1166, 2011 Sarcoid JAAD 66:699–716, 2012; AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; Clinics in Chest Medicine 18:663–679, 1997; annular atrophic plaques Cutis 103:124,130–131, 2019 Sebaceous adenitis - arcuate lesion JAAD 36:845–846, 1997 Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) - annular granulomatous papules Int J Derm 37:271–274, 1998; granuloma annulare-like lesions JAAD 37:643–646, 1997

Hepatoerythropoietic porphyria – annular plaques of nose and face BJD 151:920–923, 2004 LDH M-subunit deficiency - annular papules JAAD 41:469–473, 1999 Miescher’s granuloma Necrobiosis lipoidica diabeticorum Acta DV 58:276–277, 1978 Nephrogenic fibrosing dermopathy JAAD 58:336–339, 2008 Pruritic urticarial papules and plaques of pregnancy JAAD 10:473–480, 1984; Clin Exp Dermatol 7:65–73, 1982; JAMA 241:1696–1699, 1979 Wilson’s disease – Kayser-Fleischer ring of cornea Br Med J 289:273–276, 1984 Xanthomas, including eruptive xanthomas - personal observation

NEOPLASTIC DISEASES

Basal cell carcinoma, morpheaform - personal observation Dermatofibrosarcoma protuberans, congenital – annular red plaque, pink alopecic plaque, red macule, blue plaque, hypopigmented plaque AD 143:203–210, 2007 Desmoplastic trichoepithelioma - annular facial plaque AD 138:1091–1096, 2002; AD 132:1239–1240, 1996; Cancer 40:2979– 2986, 1977 Epithelioid sarcoma Fibrofolliculomas BJD 141:332–334, 1999 Halo nevi Keloid J Drugs Dermatol 10:468–480, 2011 Leukemia cutis including juvenile chronic myelogenous leukemia BJD 138:1058–1060, 1998; Ped Derm 7:122–125, 1990; Ped Derm 12:364–368, 1995; chronic lymphocytic leukemia – transient annular erythema with pustular folliculitis BJD 150:1129–1135, 2004 Lymphoma - cutaneous T cell lymphoma (CTCL) JAAD 72:286– 292, 2015; BJD 148:591, 2003; CTCL mimicking erythema gyratum repens (concentric annuli without scale) AD 144:673– 678, 2008; CTCL mimicking pigmented purpuric eruption Ped Derm 23:350–354, 2006; JAAD 19:25–31, 1988; CTCL mimicking granuloma annulare BJD 146:1102–1104, 2002; lymphoepithelial cell lymphoma (Lennert’s lymphoma) presenting as atypical granuloma annulare BJD 142:776–780, 2000; lymphomatoid granulomatosis (angiocentric lymphoma) AD 122:303–306,

Annular Lesions Without Surface Changes 1986; JAAD 17: 621–631, 1987; HIV-associated lymphoma Tyring, p.374, 2002; primary cutaneous B-cell lymphoma, follicular center type – stains with bcl-6 New England Dermatological Society Conference, Sept 15, 2007; BJD 157:1205–1211, 2007; Blood 105:3768–3785, 2005; J Cutan Pathol 32:647–674, 2005; cutaneous anaplastic large cell lymphoma – arciform lesions AD 145:1399–1404, 2009; primary cutaneous diffuse large cell B-cell lymphoma, leg type – large red annular patches or thin plaques JAAD 72:1016–1020, 2015; primary cutaneous CD30+ anaplastic large cell lymphoma – arciform lesions Ped Derm 26:721–724, 2009; HTLV-1 leukemia/ lymphoma - personal observation Medallion-like dermal dendrocyte hamartoma (overlap with fibroblastic connective tissue nevus) – atrophic annular plaque Ped Derm 36:397–399, 2019 Melanoma Semin Oncol 2:5–118, 1975; metastatic melanoma – erythematous annular plaques of trunk AD 148:531–536, 2012 Metastases – multiple primary systemic cancers; annular red halo after stroking neuroblastoma metastases J Ped 77:297–300, 1970 Mongolian spots - dermal melanocytosis; congenital, persistent JAAD 16:788–792, 1987; Clin Pediatr 20:714–719, 1981 Multinucleate cell angiohistiocytoma JAAD 30:417–422, 1994; Cutis 59:190–192, 1997 Primary cutaneous alveolar rhabdomyosarcoma – annular multinodular mass of chest Ped Derm 37:184–186, 2020 Sebaceous hyperplasia – annular sebaceous hyperplasias of the penis JAAD 48:149–150, 2003 Syringomas Cutis 79:369–370, 2007

PARANEOPLASTIC DISEASES Cutaneous myeloid dendritic cell dyscrasia – associated with myelodysplasia, acute or chronic myelocytic leukemia – papulonodular generalized exanthem Ann Diagn Pathol 25:85–91, 2016 Erythema gyratum repens Necrobiotic xanthogranuloma with paraproteinemia JAMA Derm 152: 589–590, 2016; SkinMed 11:121–123, 2013; AD 133:97–102, 1997 Paraneoplastic granuloma annulare – annular papules of sole JAAD 79:913–920, 2018

PHOTODERMATOSES Actinic granuloma (annular elastolytic giant cell granuloma, Miescher’s granuloma) NEJM 376:475, 2017; BJD 160:1126–1128, 2009; Eur J Dermatol 9:647–649, 1999; Cutis 62:181–187, 1998; JAAD 1:413–421, 1979; AD 111:460–466, 1975 Actinic lichen planus AD 59:308, 1989; JAAD 20:226–231, 1989 Photo-induced granuloma annulare in AIDS Polymorphic light eruption Transcutaneous oxygen monitor – photo-induced burns with annular erythema

PRIMARY CUTANEOUS DISEASES Acquired progressive kinking of the hair AD 135:1223–1226, 1999; Arch Derm Syphilogr 21:99–110, 1932 Alopecia areata Alopecia mucinosa AD 125:287–292, 1989 Annular and semicircular lipoatrophy

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Annular atrophic plaques of the face Cutis 24:90–93, 1979 Annular constriction of the glans penis JAAD 15:351–353, 1986 Annular dystrophic calcinosis in infancy JAAD 26:1015–1017, 1992 Annular erythema of infancy Clin Exp Dermatol 25:404–405, 2000; AD 123:510–3, 1987; persistent annular erythema of infancy Ped Derm 10:46–48, 1993 Annular lichenoid dermatitis of youth – red-brown annular plaques with hypopigmented centers Ped Derm 27:584–585, 2010; JAAD 49:1029, 2003 Annular lipoatrophy of the ankles Ped Derm 28:142–145, 2011; JAAD 54:S40–42, 2006; Acta DV 55:135–140, 1975; circumferential annular plaques Ped Derm 28:146–148, 2011; Clin Exp Dermatol 13:111–113, 1988; AD 102:326–329, 1970 Annular lichenoid dermatitis of youth JAAD 49:1029–1036, 2003 Atrophoderma of Pasini and Pierini Centrifugal lipodystrophy Circle hairs JAAD 634–635, 1996; JAAD 8:423–427, 1983 Circumscribed palmar or plantar hypokeratosis – red depressed or atrophic patch with ridged border JAAD 51:319–321, 2004; JAAD 49:1197–1198, 2003; JAAD 47:21–27, 2002 Eosinophilic annular erythema (annular erythema of infancy) – large annular plaques without surface change JAMA Derm 150:895–896, 2014; Actos Dermosifilogr 101:473–484, 2010; AD 117:145–148, 1981 Erythema dyschromicum perstans JAAD 21:438–442, 1989 Erythema elevatum diutinum – giant annuli JAAD 43:955–957, 2000; BJD 143:415–420, 2000 Erythema papulosa semicircularis recidivans – serpiginous annular eruption; seasonal recurrence in summer JAMA Derm 154:1340– 1341, 2018; Eur J Dermatol 26:306–307, 2016; Dermatitis 23:44– 47, 2012 Erythrokeratoderma hiemalis (erythrokeratolysis hiemalis (Oudtshoorn disease)) – palmoplantar erythema, cyclical and centrifugal peeling of affected sites, targetoid lesions of the hands and feet; annular serpiginous lesions of lower legs, knees, thighs, upper arms, shoulders – seen in South African whites; precipitated by cold weather or fever BJD 98:491–495, 1978 Erythrokeratoderma variabilis (Mendes da Costa syndrome) – autosomal dominant – dark red fixed plaques with transient polycyclic red macules with fine scale JID 113:1119–1122, 1999; Ped Derm 12:351–354, 1995 Familial annular erythema – annular urticarial plaques Ped Derm 28: 56–58, 2011; BJD 78:60–68, 1966   vs. Erythema gyratum repens – desquamation and vesiculation  vs. Annular erythema of infancy – arcuate and polycyclic plaques with central scale Cutis 44:139–140, 1989 Figurate erythema  Annular erythema of infancy JAAD 14:339–343, 1986; Ped Derm 10:46–48, 1993  Annular erythema of Sjogren’s syndrome JAAD 20:596–601, 1989   Disseminated superficial porokeratosis  Erythema annulare centrifugum (deep type) JAAD 27:281–287, 1992; Int J Derm 17:656–658, 1988, Cutis 35:53–55, 1985   Erythema chronicum migrans   Erythema gyratum atrophicans  Erythema gyratum atrophicans transiens neonatal AD 111:615– 616, 1975   Erythema gyratum perstans BJD 58:111–121, 1946  Erythema marginatum – rheumatic fever JAAD 8:724–728, 1983; Ann Int Med 11:2223–2272, 1937–1938   Erythema multiforme

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 Erythema multiforme-like lesions in sarcoid Cutis 34:461–463, 1984   Familial annular erythema BJD 78:59–68, 1966  Infantile epidermodysplastic erythema gyratum AD 120:1601– 1603, 1984 Granuloma annulare JAAD 75:457–465, 2016; BJD 152:552–555, 2005; JAAD 3:217–230, 1980; generalized granuloma annulare JAAD 57:917–918, 2007; EAC-like generalized granuloma annulare JAAD 20:39–47, 1989; GA as a tuberculid JAAD 46:948–952, 2002; photo-GA of AIDS; due to octopus bite South Med J 79:1434–1436, 1986 Granuloma faciale and extrafacial granuloma faciale JAAD 53:1002–1009, 2005; Cutis 67:413–415, 2001

CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks and arms, chondritis with progressive ear and saddle nose deformities, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, splenomegaly, protuberant abdomen JAAD 62:489–495, 2010 Ped Derm 26:654, 2009

Granuloma multiforme – upper trunk and arms; papules evolving into annular plaques with geographical, polycyclic borders; heal centrally with depigmented macules; Central Africa

Carvajal syndrome – autosomal recessive; biventricular dilated cardiomyopathy, palmoplantar keratoderma and woolly hair; mutation in desmoplakin JAAD 59:1–22, 2008

Halo scalp ring AD 123:992–993, 1987

Curled kinked and giant axonal neuropathy Arch Neurol 31:312–316, 1974

Lichen myxedematosus AD 83:230–242, 1961 Lichen planus – annular lichen planus JAAD 50:595–599, 2004; J Cutan Dis 37:639–670, 1919; atrophic lichen planus JAAD 25:392–394, 1991 Lipoatrophia semicircularis Miliaria - giant centrifugal miliaria profunda Ped Derm 7:140–146, 1990 Multiple benign annular creases of the extremities – deep creases around arms and legs Eur J Paediatr 138:301–303, 1982

Curly hair-ankyloblepharon-nail dysplasia syndrome – abnormal dentition (form of hypohidrotic ectodermal dysplasia) Birth Defects Orig Art Ser 7:100–102, 1971 Familial Mediterranean fever - annular recurrent plaque of buttocks Clin Inf Dis 58:1273–1338, 2014 Frey’s syndrome – large annular post-prandial flushing in infancy NEJM 382:1456, 2020

Neutrophilic figurate erythema of infancy Ped Derm 25:255–260, 2008; Am J Dermatopathol 19:403–406, 1997; AD 123:510–513, 1987

Hereditary angioedema – autosomal dominant; prodrome of erythema marginatum (annular urticarial eruption); facial, lip, eyelid, tongue, and hand edema NEJM 382:1136–1148, 2020; JAAD 65:843–850, 2011; Monatsh Prakt Derm 1:129–131, 1882; Edinb Med J 22:513–526, 1876

Palpable migratory arciform erythema J Drugs Dermatol 13:1288–1289, 2014; AD 133:763–766, 1977; Hum Pathol 5:25–43, 1974

Hyper IgD syndrome – periodic fever, red macules, urticaria, annular erythema, nodules, arthralgias, abdominal pain, lymphadenopathy AD 130:59–65, 1994

Relapsing annular erythema (neutrophilic figurate erythema of infancy) – facial, polycyclic borders; may be bullous, purpuric, or targetoid Ped Derm 37:209–210, 2020; recurrent annular erythema with purpura – leukocytoclastic vasculitis BJD 135:972–975, 1996; Ann DV 192:457, 2002

Hypereosinophilic syndrome - annular erythema Semin Dermatol 14:122–128, 1995

Rolled hairs JAAD 35:634–635, 1996 Sclerotic panatrophy – may follow morphea or occur spontaneously; linear or annular or circumferential bands around limbs Sock line bands of infancy – circumferential raised bands BJD 157:1063–1064, 2007; sock line hyperpigmentation AD 143:428– 430, 2007; JAAD 2:S162–164, 2007 Urticaria - personal observation Urticaria multiforme – annular, serpiginous, urticarial lesions; edema of hands, feet, face NEJM 375:470, 2016

Kawasaki’s disease - erythema multiforme-like, erythema marginatum-like, macular, morbilliform, urticarial, scarlatiniform, pustular JAAD 39:383–398, 1998 MC/MR syndrome with multiple circumferential skin creases – multiple congenital anomalies including high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals, posteriorly angulated ears, short stature, hypotonia, pectus excavatum, inguinal and umbilical hernias, scoliosis, hypoplastic scrotum, long fingers, overlapping toes, severe psychomotor retardation, resembles

Woolly hair – autosomal dominant, autosomal recessive JAAD 59:1–22, 2008; Q J Med 1:331–347, 1907; Trans St Johns Hosp Soc 60:160–177, 1974; symmetrical allotrichia (acquired progressive kinking) Cutis 24:322–324, 1979; woolly hair nevus JAAD 22:377– 381, 1990; woolly hair seen in Noonan’s, cardiofaciocutaneous, Naxos, Carvajal, and skin fragility-woolly hair syndromes JAAD 61:813–818, 2009

Menkes’ syndrome – kinky hair, characteristic face with pallor, full cheeks, cupid’s bow upper lip, lethargy, spasticity, seizures J Med Genet 34:265–274, 1997

SYNDROMES

Naxos-like disease – autosomal recessive; arrhythmogenic right ventricular cardiomyopathy, woolly hair, early-­onset blisters of knees, palms, and soles; xerosis; mutation in desmoplakin JAAD 59:1–22, 2008

Amnion rupture malformation sequence (amniotic band syndrome) - congenital ring constrictions and intrauterine amputations; secondary syndactyly JAAD 32:528–529, 1995; Cutis 44:64–66, 1989 Buschke-Ollendorff syndrome of scalp JAAD 24:882–885, 1991

Michelin tire baby syndrome Am J Med Genet 62:23–25, 1996 Naxos syndrome – autosomal recessive; woolly hair, palmoplantar keratoderma, arrhythmogenic right ventricular cardiomyopathy; mutation in plakoglobin JAAD 59:1–22, 2008; Br Heart J 56:321–326, 1986

Neurofibromatosis type I - paraspinal hair whorl indicating mediastinal plexiform neurofibroma Ped Derm 14:196–198, 1997

Annular Lesions Without Surface Changes Noonan’s syndrome – autosomal dominant; curly hair or woolly hair; dysmorphic facies, ear, eye, and cardiovascular anomalies, nevi, short stature, keratosis pilaris atrophicans, webbed neck; gain of function mutation in PTPN11 (encodes SHP-2 tyrosine phosphatase) JAAD 59:1–22, 2008; JAAD 54:S35–39, 2006

TOXINS

Reticular erythematous mucinosis (REM) syndrome

TRAUMA

Ring chromosome 13 syndrome - symmetrical arciform hypopigmentation Rubenstein-Taybi syndrome – arciform keloids, hypertrichosis, long eyelashes, thick eyebrows, keratosis pilaris or ulerythema ophyrogenes, low set ears, very short stature, broad terminal phalanges of thumbs and great toes, hemangiomas, nevus flammeus, café au lait macules, pilomatrixomas, cardiac anomalies, mental retardation Ped Derm 19:177–179, 2002; Am J Dis Child 105:588–608, 1963 Skin fragility-woolly hair syndrome – autosomal recessive; woolly hair, palmoplantar keratoderma, skin fragility; desmoplakin abnormality JID 118:232–238, 2002 Sweet’s syndrome - chronic recurrent Sweet’s syndrome of myelodysplasia; pustules, plaques, and papules AD 142:1170– 1176, 2006; histiocytoid Sweet’s syndrome – multiple deep purple plaques of hand, trunk and extremities JAMA Derm 153:651–659, 2017; JAAD 72:131–139, 2015; histiocytoid Sweet’s syndrome associated with relapsing polychondritis – annular red plaques of chest BJD 174:691–694, 2016 Tricho-dento-osseous syndrome – curly hair, hypoplastic enamel Pediatrics 37:498–502, 1966; Hum Molec Genet 7:563–569, 1998; J Med Genet 35:825–828, 1998 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) - erythematous patches, tender red plaques, fever, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia, abdominal pain, headache; Irish and Scottish predominance; mutation in TNFRSF1A - gene encoding 55kDa TNF receptor AD 136:1487– 1494, 2000 Wells’ syndrome - annular red plaques AD 142:1157–1161, 2006; AD 133:1579–1584, 1997 Winchester syndrome – annular and serpiginous thickenings of skin; arthropathy, gargoyle-like face, gingival hypertrophy, macroglossia, osteolysis (multilayered symmetric restrictive banding), generalized hypertrichosis, very short stature, thickening and stiffness of skin with annular and serpiginous thickenings of skin, multiple subcutaneous nodules JAAD 50:S53–56, 2004 Woolly hair nevus – may be associated with ipsilateral epidermal or congenital melanocytic nevus, bony abnormalities, precocious puberty, dental anomalies JAAD 59:1–22, 2008; AD 132:573–574, 1996; JAAD 27:60, 1992 Woolly hair and cardiomyopathy without keratoderma – desmoplakin mutation JAAD 59:1–22, 2008 Woolly hair and intractable diarrhea Arch Dis Child 57:212–216, 1982; J Pediatr 125:36–42, 1994 Woolly hair and keratosis pilaris (ulerythema oophyrogenes JAAD 54:S35–39, 2006 Woolly hair and skin fragility syndrome – blistering of heels and lower legs, focal and diffuse palmoplantar keratoderma; mutation in desmoplakin JAAD 59:1–22, 2008

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Dioxin exposure - erythema elevatum diutinum-like lesions JAAD 19:812–819, 1988

Annular erythema - due to impending pacemaker extrusion Acta DV 79:385–387, 1999 Bite marks – human bite marks; annular erythema with central bruising JAAD 64:811–824, 2011 Candle suction (chope) - annular skin lesions AD 120:1379–1380, 1984 Chilblains Child abuse – loop purpura JAAD 57:371–392, 2007; Ped Derm 23:311–320, 2006; linear and arcuate purpura – human bites Ped Derm 33:223–224, 2016 Cupping JAAD 57:371–392, 2007; Aust J Dermatol 12:89–96, 1971 Delayed pressure urticaria JAAD 29:954–958, 1993 Equestrian perniosis – annular, arcuate, concentric purpuric plaques of lateral thighs JAMA Derm 153:83–84, 2017 Gardner-Diamond syndrome Hardball injury – annular purpura Cutis 43:363–365, 1989 Octopus bite – resulting in granuloma annulare South Med J 79:1434–1436, 1986 Paintball purpura JAAD 53:901–902, 2005; Cutis 75:157–158, 2005 Suction purpura AD 128:822–824, 1992

VASCULAR DISEASES Acute hemorrhagic edema of infancy – annular purpura AD 146:1037–1042, 2010; JAAD 43:955–957, 2000 Capillary malformation-arteriovenous malformation syndrome – annular red patch with narrow anemic halos; RASA1 mutations Ped Derm 31:744–745, 2014; AD 148:1334–1335, 2012 Congenital self-healing tufted angioma – annular red plaque AD 142:749–751,2006 Cutaneous polyarteritis nodosa – inflammatory red plaque with peripheral nodules JAAD 60:320–325, 2009 Emboli – from cardiac myxomas; violaceous annular and serpiginous lesions BJD 147:379–382, 2002Generalized essential telangiectasia JAAD 37:321–325, 1997 Henoch-Schonlein purpura JAAD 43:955–957, 2000; rosettes AD 139:215–220, 2003 Leukocytoclastic vasculitis – annular erythema with purpura BJD 135:972–975, 1996 Pseudo-Kaposi’s sarcoma Int J Dermatol 37:223–225, 1998 Purpura annularis telangiectoides (Majocchi’s pigmented purpuric eruption) Dermatologica 140:45–53, 1970 Recurrent annular erythema with purpura BJD 135:972–975, 1996 Targetoid hemosiderotic hemangioma – annular red papule Cutis 92:91–93, 2013 Tufted angioma Dermatology 201:68–70, 2000 Urticarial vasculitis - personal observation Vasculitis - with paraproteinemia, inflammatory bowel disease, pregnancy, myeloma, sarcoid JAAD 43:955–957, 2000; leukocytoclastic vasculitis due to chlorzoxazone BJD 150:153, 2004

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ANNULAR SCARS

telangiectasia, purpura, premature graying, lymphedema AD 127:124–125, 1991; Ped Derm 13:58–60, 1996

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

NEOPLASTIC DISEASES

Lupus erythematosus - discoid lupus erythematosus NEJM 269:1155–1161, 1963; lupus profundus

Dermatofibrosarcoma protuberans arising in BCG vaccination scar AD 124:496–497, 1988

Morphea

Desmoplastic trichoepithelioma

Keloidal scleroderma (Addisonian keloid) JAAD 11:1111–1114, 1984

Kaposi’s sarcoma (papules within scars) JAAD 27:273–274, 1992 Keratoacanthoma Leukemia cutis in scar AD 123:88–90, 1987

CONGENITAL ANOMALIES Amniotic band Ped Derm 3:153–157, 1986

Lymphomatoid papulosis – papules or nodules with central necrosis Am J Dermatopathol 18:221–235, 1996; JAAD 17:632–636, 1987; JAAD 13:736–743, 1985

Aplasia cutis congenita

Nevus comedonicus with cribriform scars Ped Derm 8:300–305, 1991

Congenital varicella syndrome – pox-like scars JAAD 43:864–866, 2000; AD 126:546–547, 1990

Sebaceous carcinoma - scar-like plaque on eyelid AD 123:653–658, 1987

Trisomy 13

DRUG-INDUCED Status-post corticosteroid injections

PHOTODERMATOSES Hydroa vacciniforme - atrophic, macular, or hypertrophic scars JAAD 25:892–895, 1991; AD 114:1193–1196, 1978

D-penicillamine therapy - cribriform scars JAAD 20:979–988, 1989

PRIMARY CUTANEOUS DISEASES INFECTIONS AND INFESTATIONS Deep mycoses

Acne excoriee

Herpes simplex, resolved

Acne necrotica varioliformis - varioliform scars JAAD 16:1007–1014, 1987

Herpes zoster, healed

Acne scarring

Osteomyelitis with draining sinus tracts

Acute parapsoriasis (pityriasis lichenoides et varioliformis acuta) (Mucha-Habermann disease) AD 123:1335–1339, 1987; AD 118:478, 1982

Papulonecrotic tuberculid - varioliform scars JAAD 14:815–826, 1986 Pyodermas Smallpox Syphilis, tertiary

INFILTRATIVE DISEASES Disseminated xanthosiderohistiocytosis (form of xanthoma disseminatum)- keloidal plaques JAAD 11:750–755, 1984

INFLAMMATORY DISEASES Pancreatic panniculitis, healed Pyoderma gangrenosum - cigarette paper scars JAAD 18:559–568, 1988 Sarcoidosis

METABOLIC DISEASES Necrobiosis lipoidica diabeticorum Porphyria - erythropoietic protoporphyria Eur J Pediatr 159:719– 725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751– 766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976; congenital erythropoietic porphyria - shallow facial scars AD 128:1243–1248, 1992 Prolidase deficiency – autosomal recessive; skin spongy and fragile with annular pitting and scarring; leg ulcers; photosensitivity,

Anetoderma of Jadassohn Aplasia cutis congenita Textbook of Neonatal Dermatology, W.B. Saunders, pp. 126–127, 2001   Type 1 - ACC of scalp without multiple anomalies   Type 2 - ACC of scalp with limb reduction abnormalities   Type 3 - ACC of scalp with epidermal and organoid nevi   Type 4 - ACC with overlying developmental malformations   Type 5 - ACC with fetus papyraceus or placental infarcts   Type 6 - ACC with epidermolysis bullosa   Type 7 - ACC due to teratogens   Type 8 - ACC due to intrauterine infections   Type 9 - ACC as feature of malformation syndromes   Junctional EB with pyloric atresia   ACC localized to extremities without blistering (group 7)   Adams-Oliver syndrome – large irregular scalp defects; distal limb reduction abnormalities   Chromosome 16–18 defect – large scalp defects; arteriovenous malformation of scalp with underlying bony defect   Trisomy 13 (trisomy D (13–15)) – membranous aplasia cutis; holoprosencephaly, seizures, ocular abnormalities, deafness, neural tube defects   Deletion of short arm of chromosome 4 (4p (-) syndrome) – mental retardation, deafness, seizures, ocular abnormalities   Oculocerebrocutaneous syndrome – membranous aplasia cutis; orbital cysts, cerebral malformations, facial skin tags, seizures, developmental delay   Opitz syndrome – membranous aplasia cutis; hypertelorism, cleft lip/palate, hypospadias, cryptorchidism

Aortic Disease in the Young   Johnson-Blizzard syndrome – small stellate defects; membranous aplasia cutis; dwarfism, mental retardation, deafness, hypothyroidism, pancreatic insufficiency    Focal dermal hypoplasia    Bitemporal aplasia cutis congenita (Setleis syndrome)    Focal facial dermal dysplasia    Amnion rupture malformation sequence   Congenital erosive and vesicular dermatosis with reticulate supple scarring    Lumpy scalp, odd ears, and rudimentary nipples   Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome   Scalp-ear-nipple syndrome – autosomal dominant; aplasia cutis congenita of the scalp, irregularly shaped pinna, hypoplastic nipple, widely spaced teeth, partial syndactyly Am J Med Genet 50:247–250, 1994    Tricho-odonto-onychodermal dysplasia syndrome    Others - cleft lip and palate, ear pits, ear deformities   Xp22 microdeletion syndrome – bilateral linear defects of malar region; microphthalmia, sclerocornea Atrophia maculosa varioliformis cutis Atrophoderma of Pasini and Pierini Collagenome perforante verruciform Ann DV 90:29–36, 1963 Epidermolysis bullosa - benign juvenile epidermolysis bullosa - cigarette paper scars JAAD 14:508–509, 1986; cicatricial junctional epidermolysis bullosa JAAD 12:836–844, 1985; epidermolysis bullosa dystrophica inverse - pitted heel scars AD 124:544–547, 1988; dominant dystrophic epidermolysis bullosa; junctional epidermolysis bullosa Familial acne conglobata - pitted antecubital scars JAAD 14:207– 214, 1986

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VASCULAR Atrophie blanche en plaque Degos’ disease Livedo vasculitis AD 124:684–687, 1988 PHACES syndrome – annular ventral scars with infantile hemangiomas around them Sem Cut Med Surg 35:108–116, 2016 Granulomatosis with polyangiitis Vasculitis, including koebnerization of leukocytoclastic vasculitis lesions within scars JAAD 22:775–781, 1990

AORTIC DISEASE IN THE YOUNG Int J Vasc Med 2013; Article ID 267215 Ankylosing spondylitis – associated findings include psoriasis, anterior uveitis, inflammatory bowel disease, lung abnormalities, heart conduction defects, aortic insufficiency, renal abnormalities, osteoporosis, vertebral fractures Euro J Intern Med 2011:1–7; Int J Rheumatol 2011:1–10 Axenfeld-Rieger syndrome FOXC1 mutation; autosomal dominant; ophthalmic anterior segment abnormalities, dental anomalies, redundant periumbilical skin Am J Med Genetics A 161A:114–119, 2013 Bacterial endocarditis Behcet’s disease – aortic valve regurgitation, aortic root dilatation, pulmonary artery aneurysms, intracardiac thrombi Echocardiography 31:783–787, 2014 Bicuspid aortic valve

Focal facial dermal dysplasias JAAD 27:575–582, 1992; bitemporal scarring JAAD 18:1203–1207, 1988

Bier’s spots and hypoplasia of the aorta Dermatology 215:166–167, 2007

Hidradenitis suppurativa

Cutis laxa type 1B (ARCL1B) – mutations in EFEMP2 (FBLN4) gene; aortopathy with aneurysm formation and vascular tortuosity Eur J Pediatr 173:671–675, 2014

Mid-dermal elastolysis - wrinkled scars JAAD 26:169–173, 1992 Pityriasis rosea, vesicular

PSYCHOCUTANEOUS DISEASES Factitial dermatitis

SYNDROMES Behcet’s syndrome Dowling-Degos syndrome - pitted scars Ehlers-Danlos syndrome Goltz’s syndrome - annular atrophic plaques Cutis 53:309–312, 1994 Lipoid proteinosis – pock-like annular scars Acta Paediatr 85:1003– 1005, 1996; JAAD 27:293–297, 1992 Progeria - scars and keloid-like lesions AD 124:1261–1266, 1988

TRAUMA Amniocentesis scar Drug abuse - skin popping Paintball injury – annular white scars Cutis 80:49–50, 2007

DOCK 8 deficiency Dermatol Clinics 35:11–19, 2017 Ehlers-Danlos syndrome  Classical  Hypermobile  Vascular (EDS type IV) – autosomal dominant; mutations in COL3A1 Epidermolysis bullosa – dystrophic, junctional; dilated cardiomyopathy; ventricular dysfunction and aortic dilatation BJD 174:671–673, 2016; Ped Derm 27:238–243, 2010 Fabry’s disease – alpha-galactosidase A deficiency Curr Pharm Des 19:5974–5976, 2013 Familial aortic aneurysm and/or dissection syndromes (FAAD) – ascending aorta TGFBR2, MYH11, ACTA2 Homozygous familial hypercholesterolemia – aortic stenosis Hunter syndrome – deficiency of lysosomal enzyme iduronate2-sulphatase; coarse facial features; ivory colored skin papules of upper back and sides of arms; umbilical and inguinal hernias, coarse straight bristly hair; short stature, joint stiffness, short neck, broad chest, skeletal changes, progressive and profound mental retardation, retinal degeneration, hearing loss, cardiomyopathy, mitral and aortic regurgitation and stenosis Pediatr Endocrinol Rev 12:107–113, 2014 Hypotrichosis-Lymphedema-Telangiectasia-Renal failure syndrome – diffuse reticulated capillary malformation, hypertensive emergency with transient ischemic attack, dilatation or aortic root, pleural effusions, acute kidney injury, thin facies with telangiectasias

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of cheeks, livedo reticularis of trunk and extremities; mutation in SOX18 gene Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016 IgG4-related disease – aortitis; papules, nodules, plaques JAMA Derm 156:451, 2020; JAAD 75:197–202, 2016; NEJM 373:1762– 1772, 2015; Radiology 261:625–633, 2011 Loeys-Dietz syndrome – autosomal dominant; premature and aggressive aortic aneurysms; autosomal dominant; TGFBR1 or TGFBR2 (transforming growth factor beta receptor genes); marfanoid habitus, delicate triangular face, multiple facial milia, velvety and translucent skin, easy bruising, varicose veins, atrophic scars, malar hypoplasia, retrognathia, craniosynostosis, hypertelorism, cleft lip and palate, bifid uvula, malar hypoplasia, blue sclerae, arachnodactyly, joint laxity, pectus deformities, scoliosis, camptodactyly, high arched palate, aortic root aneurysm and dissection, arterial tortuosity JAMA Derm 151:675– 676, 2015; AD 147:223–226, 2011; JAAD 59:1050–1063, 2008; JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005; mutations in transforming growth factor beta receptor genes 1 and 2; widely spaced eyes, increased signaling of TGF beta and overproduction of collagen, loss of elastin and disarray of elastic fibers Marfan’s syndrome – fibrillin 1 mutation (FBN1) gene; ascending aortic aneurysm Am J Med 126:670–678, 2013 Marshall’s syndrome – neutrophilic dermatosis with cutis laxa; aortic disease and other aneurysms Ped Derm 32:437–446, 2015; S Afr Med J 40:1016–1022, 1966 Minocycline (lifelong) – black pigmented aortic valve Interact Cardiovasc Thorac Surg 19:339–340, 2014

APHTHOUS STOMATITIS JAAD 52:500–508, 2005; JAAD 40:1–18, 1999

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSREGULATION Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – loss of function mutation in cat eye syndrome chromosome candidate 1 gene (CECR1); painless leg nodules with intermittent livedo reticularis, Raynaud’s phenomenon, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae; vasculitis of small and medium arteries with necrosis, fever, early recurrent ischemic and hemorrhagic strokes, peripheral and cranial neuropathy, and gastrointestinal involvement (diarrhea); hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:199–201, 2020; NEJM 380:1582–1584, 2019; Ped Derm 33:602–614, 2016; NEJM 370:911–920, 2014; NEJM 370:921–931, 2014 Food allergies NEJM 369:265–274, 2013 Systemic lupus erythematosus Mucous membrane pemphigoid NEJM 369:265–274, 2013 Pemphigus vulgaris X-linked chronic granulomatous disease - discoid lupus-like lesions of face and hands in female carriers of X-linked chronic granulomatous disease BJD 104:495–505, 1981

Neurofibromatosis Ochronosis (alkaptonuria) – deficiency of homogentisic acid oxidase; dark brown color of urine; aortic valve stenosis, regurgitation

DRUGS Azithromycin

Osteogenesis imperfecta – aortic dissection Am J Med Sci 336:70–72, 2008

Captopril Lancet Dec15;2 (8155)):1297–1298, 1979

Pallister-Killian syndrome – facial dysmorphism, diaphragmatic hernia, congenital heart defects, hypotonia, hearing loss, seizures, differences in skin pigmentation, temporal alopecia Am J Med Genetic A 164A:1130–1135, 2014

Doxorubicin

PHACES syndrome – aortic coarctation, aneurysm, aberrant origin of subclavian artery Sem Cut Med Surg 35:108–116, 2016; Curr Med Chem 21:3153–3164, 2014

Docetaxel 5-fluorouracil Gold Imiquimod JAAD 53:360–361, 2005 Losartan Clin Nephrol 50:197, 1998 Methotrexate

Autosomal dominant polycystic kidney disease – PKD1 AND PKD2

Mycophenolate mofetil

Progeria J Pak Med Assoc 63:1182–1185, 2013

Nicorandil (potassium channel blocker) BJD 138:712–713, 1998

Pseudoxanthoma elasticum Arterioscler Thromb Vasc Biol 33:2646–2652, 2013

NSAIDS- naproxen

Psoriasis – increased risk of aortic aneurysm JAAD 75:747–754, 2016

Piroxicam JAAD 50:648–649, 2004

Reactive arthritis – aortic insufficiency

Sirolimus - personal observation

Relapsing polychondritis – regurgitation or aneurysm

Trimethoprim-sulfamethoxazole

Penicillamine Br Dent J 149:180–181, 1980

Sarcoidosis – childhood aortic abdominal aneurysm (large vessel vasculitis) Clin Rheumatol Jan 24,2015 Singleton-Merten syndrome – psoriatic skin lesions, aortic calcification, supra-aortic stenosis BMJ Case Rep Sept 5, 2014 Syphilitic aortitis – secondary syphilis JAMA Derm 150:790–791, 2014 Takayasu’s arteritis J Rheumatol 40:734–738, 2013 Turner’s syndrome – coarctation of the aorta JAAD 74:231–244, 2016 Varicella, congenital – patent ductus arteriosus NEJM 375:1468, 2016

EXOGENOUS AGENTS Fluoride Dermatology 208:181, 2004 Foreign bodies at distant locations Intrauterine device Contact lenses Lancet 1:857, 1974 Smoking cessation Tobacco Control 12:86–88, 2003 Sodium lauryl sulfate in dentifrices NEJM 369:265–274, 2013

Aphthous Stomatitis

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 autoimmune Oral Surg Oral Med Oral Pathol 78:178–180, 1994

AIDS J Oral Pathol Med 21:409–411, 1992

 cyclic

Chikungunya fever JAAD 75:1–16, 2016

 chemotherapy-induced

Cytomegalovirus, including aphthous ulcer of the tongue Otolaryngol Head Neck Surg 110:463–464, 1994

Zinc deficiency Oral Surg Oral Med Oral Pathol 72:559–561, 1991

Dengue fever - hyperpigmentation of nose (chik sign); transient flushing, purpuric lesions, scleral injection, morbilliform exanthem with circular islands of sparing, aphthous ulcers, lichenoid papules, flagellated pigmentation, urticarial lesions, erythema multiforme-like Ped Derm 36:737–739, 2019; Indian Dermatol Online J 8:336–342, 2017; Indian J DV Leprol 76:671–676, 2010

Steatorrhea BJD 78:546–547, 1966

NEOPLASTIC DISEASES Carcinoma Dent Update 19:353, 1992

Hand, foot, and mouth disease – Coxsackie A16, Enterovirus 71, Coxsackie A6 JAAD 75:1–16, 2016; NEJM 369:265–274, 2013

PRIMARY CUTANEOUS DISEASES

Herpes simplex

Aphthae – major, minor, herpetiform

Histoplasmosis Ned Tijdschr Geneeskd 144:1201–1205, 2000

Idiopathic Dermatol Clin 5:761–768, 1987

HIV disease NEJM 369:265–274, 2013; HIV thrombotic vasculopathy with major aphthae - personal observation

Pityriasis rosea AD 122:503–504, 1986

Mycobacterium tuberculosis

Recurrent aphthous stomatitis Ped Derm 36:986–987, 2019; Ped Derm 32:476–480, 2015; AD 147:282–283, 2011

Myospherulosis Int J Oral Maxillofacial Surg 22:234–235, 1993 Paracoccidioidomycosis Parvovirus B19 – bullous papular-purpuric gloves and socks syndrome JAAD 60691–695, 2009 Rhinoscleroma Rhinosporidiosis Syphilis – primary, secondary, or tertiary; including endemic syphilis (bejel) Ulcus vulvae acutum JAAD 52:500–508, 2005 Vitamin B1, B2, B6, and B12 deficiency Clinics in Derm 17:457– 461, 1999; South Med J 83:475–477, 1990 Yersinia enterocolita

Primary complex aphthosis

Sutton’s disease (periadenitis mucosa necrotica recurrens) AD 133:1162–1163, 1165–1166, 1997

SYNDROMES Behcet’s syndrome - JAAD 77:809–830, 2017 Cancrum oris (noma) Br J Plast Surg 45:193–198, 1992 FAPA – periodic fever, aphthosis, stomatitis, pharyngitis, adenitis; predominantly in young children J Pediatr 146:283–285, 2005; JAAD 52:500–508, 2005 Hypereosinophilic syndrome Eur J Dermatol 13:207–208, 2003 MAGIC syndrome – mouth and genital ulcers with inflamed cartilage JAAD 52:500–508, 2005

INFILTRATIVE DISORDERS

Muckle-Wells syndrome Am J Med Genet 53:72–74, 1994

Orofacial granulomatosis – oral ulcers, aphthous ulcers, swollen lip (s), gingivitis, and/or gingival hypertrophy JAAD 62:611–620, 2010

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) NEJM 369:265–274, 2013; Curr Opin Pediatr 12:563–566, 2000; Curr Opin Pediatr 12:253–256, 2000; J Pediatr 135:98–101, 1999 Reactive arthritis

INFLAMMATORY DISORDERS Crohn’s disease JAAD 77:795–806, 2017; NEJM 369:265–274, 2013; Eur J Dermatol 8:1238–1240, 1998; NEJM 330:1870, 1994 Erythema multiforme NEJM 369:265–274, 2013 Ulcerative colitis Indian J Gastroenterol 10:88–89, 1991

METABOLIC DISEASES

Relapsing polychondritis with or without associated Behcet’s disease Am J Med 79:665, 1985; J Rheum 4:559, 1984 Sweet’s syndrome Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) J Ped 146:283–285, 2005

TRAUMA

Agranulocytosis

Bednar’s ulcer – palatal aphthous ulcer in infant; due to trauma from pacifier Ped Derm 37:213–214, 2020

Celiac disease (gluten-sensitive enteropathy) NEJM 369:265–274, 2013 Eur J Oral Sci 106:899–906, 1998; BJD 103:111, 1980

Radiation ulcer

Cyclic neutropenia JAAD 52:500–508, 2005

Trauma – biting the lip

Fanconi’s anemia Int J Ped Dent 14:214–217, 2004 Folate deficiency JAAD 52:500–508, 2005

VASCULAR DISORDERS

Inflammatory bowel disease

Granulomatosis with polyangiitis

Iron deficiency NEJM 369:265–274, 2013; JAAD 52:500–508, 2005

Polyarteritis nodosa Oral Surg 56:597–601, 1983; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon,

Luteal phase of the menstrual cycle Neutropenia

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digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014

 RTHRITIS AND RASH A (POLYARTHRITIS AND MONOARTHRITIS)  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Angioedema AD 134:929–931, 1998 Antineutrophil cytoplasmic antibody syndrome – polyarthritis, purpuric vasculitis, orogenital ulceration, fingertip necrosis, pyoderma gangrenosum-like ulcers BJD 134:924–928, 1996 APLAID (autoinflammation and PLAID) – sinopulmonary infections, interstitial pneumonitis, eye inflammation, colitis, arthralgias; epidermolysis bullosa-like eruptions in infancy with vesiculopustular lesions and red plaques JAAD 73:367–381, 2015 Autoimmune hepatitis – itching, fatigue, lethargy, anorexia, nausea, abdominal pain, and arthralgia NEJM 354:54–66, 2006 Autoimmune progesterone dermatitis AD 107:896, 1973 Bowel arthritis-dermatitis syndrome - pustular vasculitis, erythema nodosum-like lesions; tenosynovitis, non-­destructive polyarthritis BJD 142:373–374, 2000; AD 135:1409–1414, 1999; Cutis 63:17– 20, 1999; JAAD 14:792–796, 1986; Mayo Clin Proc 59:43–46, 1984; AD 115:837–839, 1979 Common variable immunodeficiency BJD 144:597–600, 2001 Deficiency of interleukin-1 receptor antagonist (DIRA) (IL-1 receptor deficiency) – loss of function mutation of IL1RN; neutrophilic pustular dermatosis with confluent pustules and lakes of pus; infantile pustulosis and exfoliative erythroderma; oral ulcers, joint swelling; periostitis, aseptic multifocal osteomyelitis; increased acute phase reactants Ped Derm 30:758–760, 2013; AD 148:747–752, 2012 Dermatomyositis – bursitis of shoulders and hips, joint effusions Rook p. 2558, 1998, Sixth Edition; Am J Med 67:287–292, 1979; arthralgias JAAD 51:427–439, 2004; periorbital edema and arthralgias of dermatomyositis with anti-PL-12 autoantibodies (antisynthetase syndrome) NEJM 367:2134–2146, 2012; tender hyperkeratotic palmar papules in palmar creases of fingers with central white coloration; dermatomyositis with MDA-5 (CADM-40) (melanoma differentiation-associated gene 5) MDA 5 – RNAspecific helicase; all with interstitial lung disease; ulcers of nail folds, Gottron’s papules, and elbows; these patients demonstrate oral ulcers, hair loss, hand edema, arthritis/arthralgia, diffuse hair loss, punched out ulcers of shoulder or metacarpophalangeal joints, digital necrosis, erythema of elbows and knees (Gottron’s sign), and tender gingiva JAAD 78:776–785, 2018; JAAD 65:25–34, 2011 Familial chilblain lupus – autosomal dominant; violaceous erythema and scaling of toes; ulcers, arthralgias and arthritis; mutation in SAMHD1 and TREX 1 Ped Derm 33:602–614, 2016 Fogo selvagem (endemic pemphigus) - arthralgias JID 107:68–75, 1996; JAAD 32:949–956, 1995 Gain of function mutation of NLRC4 (inflammasome) – fever, periodic urticarial rash, conjunctivitis, arthralgias, painful red nodules of foot or leg, enterocolitis, splenomegaly, macrophage activation syndrome; increased IL-18 BJD 176:244–248, 2017; Nat

Genet 46:1135–1139, 2014; Nat Genet 46:1140–1146, 2014; J Exp Med 211:2385–2396, 2014 Graft vs, host disease, chronic – joint stiffness JAAD 66:515–532, 2012 H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism and azoospermia; short stature; mutation in SLC29A3 gene (equilabrative nucleoside transporter) Arabic Palestinian population; gluteal lipoatrophy; diabetes mellitus, lymphadenopathy, chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 Ped Derm 33:602–614, 2016; JAAD 70;80–88, 2014; BJD 162:1132–1134, 2010; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008 Hyper-IgD syndrome – autosomal recessive; oral ulcers; myositis, myalgias; urticarial plaques; abdominal pain, vomiting, diarrhea; arthralgias; recurrent transient and fixed pink plaques and nodules of face and extremities; cephalic pustulosis; mevalonate kinase deficiency; red macules or papules, urticaria, red nodules, urticaria, combinations of periodic fever, arthritis, arthralgias, and rash, annular erythema, and pustules, abdominal pain with vomiting and diarrhea, lymphadenopathy; elevated IgD and IgA - mevalonate kinase deficiency Ped Derm 35:482–485, 2018; Ped Derm 22:138–141, 2005; AD 136:1487–1494, 2000; AD 130:59–65, 1994; Medicine 73:133–144, 1994; Lancet 1:1084–1090, 1984 Hyper IgE syndrome – hyperextensible joints JAAD 54:855–865, 2006; Pediatr 141:572–575, 2002; Curr Prob in Derm 10:41–92, 1998 IgG4 disease – joint effusions, lymphadenopathy, enlarged nodular temporal arteritis, lacrimal gland enlargement, enlarged sublingual glands, palpable purpura NEJM 376:775–786, 2017 Juvenile rheumatoid arthritis (Still’s disease) - salmon pink macules, papules, evanescent non-pruritic, not migratory, with single or double quotidian fever with wide diurnal swings ("resident’s rash"); on trunk, extremities; pressure areas; pharyngitis at presentation; migratory arthritis becomes chronic, lymphadenopathy, neutrophilic leukocytosis, elevated ESR (2/3 of patients with ESR of 100 or greater), elevated liver function tests, elevated ferritin Med Chir Trans 80:47, 1897; urticaria Clin Rheumatol 19:389–391, 2000 Linear IgA disease BJD 119:789–792, 1988 Lupus erythematosus – systemic; discoid lupus erythematosus; NEJM 269:1155–1161, 1963 Mixed connective tissue disease Am J Med 52:148–159, 1972 Morphea JAAD 47–51, 2018; AD 145:127–130, 2009; Semin Cutan Med Surg 26:90–95, 2007; Mayo Clin Proc 70:1068–1076, 1995; pansclerotic morphea – mutilating form of morphea AD 116:169– 173, 1980; generalized morphea Pemphigus vulgaris - association with autoimmune thyroid disease, rheumatoid arthritis, type 1 diabetes mellitus BJD 172:729–738, 2015 Relapsing polychondritis - auricular chondritis limited to cartilagenous portion of ears with lobules spared; erythema may involve retroauricular soft tissues; residual permanent induration (cauliflower ear); nasal chondritis with saddle nose deformity; seronegative, non-destructive arthritis; non-nodular, asymmetric without

Arthritis and Rash (Polyarthritis and Monoarthritis) deformity; polyarthralgia - mimics rheumatoid arthritis; involves costal cartilage, sternoclavicular, manubrial-sternal joint

Minocycline-induced p-ANCA+ cutaneous polyarteritis nodosa (vasculitis) JAAD 48:311–340, 2003; JAAD 44:198–206, 2001

Rheumatoid arthritis-associated lesions   Rheumatoid neutrophilic dermatitis   Rheumatoid vasculitis   Dawson’s palms (palmar erythema)   Yellow discoloration of skin   Skin transparency

Non-pigmenting fixed drug eruption

Subcutaneous nodules   Sweet’s syndrome   Erythema elevatum diutinum   Pyoderma gangrenosum Scleroderma – systemic sclerosis – arthralgia NEJM 372:1056–167, 2015; nodular scleroderma JAAD 66:959–965, 2012; tenderness and swelling of joints as presenting signs Serum sickness NEJM 311:1407–1413, 1984; Dermatol Clin 3:107–117, 1985; associated with hepatitis B Arch Int Med 141:623–629, 1981 Sjogren’s syndrome – arthritis and arthralgias A Clinician’s Pearls and Myths in Rheumatology pp.107–130; ed John Stone; Springer 2009 X-linked chronic granulomatous disease - discoid lupus-like lesions of face and hands in female carriers of X-linked chronic granulomatous disease BJD 104:495–505, 1981 X-linked hypogammaglobulinemia (agammaglobulinemia) J Allergy 33:406–411, 1962

DEGENERATIVE DISEASE Osteoarthritis - Heberden’s nodes on DIP joints; Bouchard’s nodes on PIP joints

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Propylthiouracil vasculitis – blue necrotic ear lesions; fever, arthralgias, and myalgias JAMA Derm 151:551–552, 2015 RAF inhibitors (MAPK pathway) – vemurafenib and dabrafenib – exanthema warts and other hyperkeratotic lesions, keratoacanthomas, squamous cell carcinoma, melanocytic nevi, keratosis pilaris, seborrheic dermatitis, hyperkeratotic hand-foot reactions, photosensitivity, panniculitis with arthralgias, alopecia JAAD 72:221–236, 2015 Sweet’s syndrome – drug-induced JAAD 34:918–923, 1996 Voriconazole-induced fluoride excess; periostitis with swollen joints of hands Clin Inf Dis 57:562–563,616–617, 2013 Ustekinumab BJD 168:21–212, 2013 Vemurafenib – panniculitis with arthralgias AD 148:363–366, 2012

EXOGENOUS AGENTS Epoxy resin-associated fibrosis with arthralgia Dermatologica 161:33–44, 1980 Levamisole vasculopathy JAAD 67:791–792, 2012; Ann Int Med 152:758–759, 2010; JAAD 63:530–535, 2010 Plants – sharp-tipped leaves of palms or yuccas, rose thorns – deeply embedded - septic arthritis mimicking bony tumor J Bone Joint Surg Am 34:386–388, 1952 Sea urchin spine granulomas – initial edema; delayed onset of bluish papules and nodules (granulomas); fusiform swelling of digits (synovitis) Clin Exp Dermatol 2:405–407, 1977; tenosynovitis and arthritis Joint Bone Spine 67:94–100, 2000 Silicone gel breast implants - fever, rash, and arthritis West J Med 167:149–158, 1997

DRUG Azathioprine hypersensitivity reaction – occurs within first four weeks of treatment; fever, malaise, arthralgias, myalgias, nausea, vomiting, diarrhea; morbilliform eruption, leukocytoclastic vasculitis, acute generalized exanthematous pustulosis, erythema nodosum, Sweet’s syndrome Clin Inf Dis 68:1427–1430, 2019; JAAD 65:184–191, 2011 BCG vaccination – morbilliform or purpuric eruptions with arthralgia, abdominal pain BJD 75:181–192, 1963; lichenoid and red papules and papulopustules Ped Derm 13:451–454, 1996 BRAF inhibitors (vemurafenib or dabrafenib) – panniculitis and arthralgia AD 148:357–361, 2012 Drug hypersensitivity syndrome AD 132:1315–1321, 1996 Infliximab – polyarthritis and abscess formation during infliximab treatment of hidradenitis suppurativa BJD 165:194–198, 2011 Intralesional corticosteroid - periarticular rash Arthritis Rheum 26:231–233, 1983 Isotretinoin therapy for acne vulgaris – sacroiliitis Ped Derm 37:171–175, 2020; JAAD 15:1061–1062, 1986 Jarisch-Herxheimer reaction – treatment of syphilis, onchocerciasis, Lyme disease, strongyloidiasis AD 125:77–81, 1989; Hautarzt 35:588–590, 1984 Methotrexate osteopathy in low dose treatment of psoriasis AD 132:184–187, 1996 Minocycline hypersensitivity syndrome or lupus-like syndrome Br Med J 312:169–172, 1996; BJ Rheumatol 674–676, 1994

INFECTIONS AND INFESTATIONS Actinomycosis of long duration Clin Inf Dis 27:889, 1998 Acute bacterial endocarditis Adenovirus infection African histoplasmosis African tick bite fever (Rickettsia africae) – hemorrhagic pustule, purpuric papules; transmitted by Amblyomma ticks) – high fever, arthralgia, myalgia, fatigue, rash in 2–3 days, with eschar, maculopapules, vesicles, and pustules JAAD 48:S18–19, 2003 Arbovirus fever  Dengue fever (flavivirus) – in first 24 hours, flushing of face, neck, and chest; morbilliform or scarlatiniform eruption on day 3–4, then becomes petechial; classic dengue fever with joint and bone pain (breakbone fever) with severe backache JAAD 58:308–316, 2008; JAAD 49:979–1000, 2003; JAAD 46:430–433, 2002; Bull Soc Pathol Exot 86:7–11, 1993  Mayaro virus – arbovirus; fever, headache, myalgia, arthralgia; exanthema of trunk and extremities; Brazil and Trinidad JAAD 58:308–316, 2008  O’Nyong-Nyong fever –fever, arthritis, lymphadenopathy; morbilliform exanthem of face, trunk, extremities, especially the neck, back, inner thighs, and arms; sub-Saharan Africa JAAD 58:308–316, 2008 Oropouche fever Phlebotomus fever

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 Ross River virus fever (disease) (togavirus) - fatigue, arthralgia, arthritis, morbilliform eruption of trunk, palms and soles, face, and scalp JAAD 58:308–316, 2008; Clin Rheum Dis 12:369–388, 1986; Australia – mosquito-­borne Emerging Inf dis 25:1793– 1801, 2019  Sindbis – fever, rash, arthritis; Europe, Asia, Africa, Australia  Togavirus - morbilliform, maculopapular-petechial (Sindbis BJD 135:320–323, 1996; BJD 80:67–74, 1968; chikungunya Trans R Soc Trop Med Hyg 49:28–32, 1955; and O’Nyong-Nyong fever Trans R Soc Med Hyg 55:361–373, 1961; bunyavirus fevers) with joint pains; West Nile fever JAAD 51:820–823, 2004 Barmah Forest virus – similar to Ross River virus Med J Aust 152:463–466, 1990 Bee and wasp stings – serum sickness as late onset manifestation NEJM 133:523–527, 1994; J Allergy Clin Immunol 84:331–337, 1989 Bejel (endemic syphilis) Black widow spider bite – lactrodectism; pruritus, urticarial, diaphoresis, severe muscle cramping, joint stiffness, headache, nausea, vomiting Am J Emerg Med 30:836e1–2, 2012 Brown recluse spider bite – purpuric morbilliform eruption in children at 24–48 hours JAAD 44:561–573, 2001 Calymmatobacterium granulomatis (Donovanosis) - joint pain and swelling J Clin Inf Dis 25:24–32, 1997 Candida - disseminated Candidiasis JAAD 26:295–297, 1992 Capnocytophagia canimorsus Eur J Epidemiol 12:521–533, 1996 Cat scratch disease – Bartonella henselae; red papule, becomes vesicle, crusts, ulcerates, heals with scar Am J Dis Child 139:1124– 1133, 1985; JAMA 154:1247–1251, 1954 Caterpillars – dendrolimiasis (Masson pine caterpillar (Dendrolimus) and Premolis semirufa (Amazon region) caterpillar hairs – periarticular fibrosis and ankylosis of hand (pararama) JAAD 67:331–344, 2012; JAAD 62:1–10, 2010 Chagas’ disease - personal observation Chikungunya fever - morbilliform exanthem of trunk and limbs with islands of sparing; high fever, headache, photophobia, myalgia, arthralgias and arthritis of large joints with periarticular erythema; severe joint pain lasting up to 2 years; purpuric butterfly rash of face with necrosis of skin of nose JAAD 75:1–16, 2016; Clin Inf Dis 62:78–81, 2016; NEJM 372:1657–1664, 2015; JAMA Derm 151:257–258, 2015; Ped Derm 33:238–240, 2016;- JAAD 58:308– 316, 2008; Clin Inf Dis 20:225–231, 1995  Fever, flush of face and upper chest, chills, severe pain in large joints  Maculopapular eruption of the trunk, extensor surfaces with islands of sparing; burning pinnae, severe conjunctival injection   East Africa, India Coccidioidomycosis – tenosynovitis of hand and wrist Clin Inf Dis 61:1514–1520, 2015 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of fingers, palmar erythema, red papules of ears, red papules of antecubital fossa, perioral papulovesicles, vesicles of posterior pharynx; crusted papules of scalp, ears, and face; purpuric targetoid painful vesicular lesions of hands and feet, arthritis, fissured scrotum; headache, arthralgias JAMA Derm 153:219–220, 2017; J Clin Virol 60:381–386, 2014; J Clin Virol 59:201–203, 2014; JAMA Derm 149:1419–1421, 2013; JAAD 69:736–741, 2013; MMWR 61:213–214, 2012 Cryptococcosis, disseminated J Inf Dis 56:117,159–160, 2013 Dematiaceous fungal infections in organ transplant recipients - all lesions on extremities - bursitis, synovitis   Alternaria

         

Bipolaris hawaiiensis Exophiala jeanselmei, E. spinifera, E. pisciphera, E. castellani Exserohilum rostratum Fonsacaea pedrosoi Phialophora parasitica

Dirofilaria – parasitic rheumatism Cutis 72:269–272, 2003; subcutaneous dirofilariasis JAAD 35:260–262, 1996 Dracunculosis (Dracunculus medinensis) (Guinea worm) – migration of this nematode into joints Dermatol Clinic 7:323–330, 1989; swollen knee with linear periarticular calcifications Clin Inf Dis 57:1308,1362, 2013 Ebola virus hemorrhagic fever (Filovirus) – exanthem which becomes purpuric with desquamation of palms and soles; high fever, body aches, myalgia, arthralgias, prostration, abdominal pain, watery diarrhea; disseminated intravascular coagulation Int J Dermatol 51:1037–1043, 2012; JAMA 287:2391–2002; Int J Dermatol 51:1037–1043, 2012; JAAD 65:1213–1218, 2011; MMWR 44, No.19, 382, 1995 Echovirus Erysipeloid Glanders – Pseudomonas mallei – cellulitis which ulcerates with purulent foul-smelling discharge, regional lymphatics become abscesses; nasal and palatal necrosis and destruction; metastatic papules, pustules, bullae over joints and face, then ulcerate; deep abscesses with sinus tracts occur; polyarthritis, meningitis, pneumonia Gonococcemia - acral purpuric vesicles, pustules, gray necrotic centers, hemorrhagic bullae; mean number of lesions is 10–16; skin lesions resolve in 3–5 days; polyarticular arthritis, especially wrist, ankle, extensor tendon sheaths, tenosynovitis; monoarticular arthritis; women during or after menses; men having sex with men Am Fam Phys 34:77–79, 1986 Helicobacter cinaedi - cellulitis and monoarticular arthritis Clin Inf Dis 20:564–570, 1995 Hepatitis A JAAD 37:659–661, 1997 Hepatitis B - serum sickness with angioneurotic edema - reticulated fine red blanching erythema; urticaria - "yellow hives, morbilliform eruptions; nonthrombocytopenic petechiae; pruritus; fever, myalgias, acute migratory or additive polyarthritis which subsides with onset of jaundice NEJM 368:1239–1245, 2013; JAAD 8:539–548, 1983 Hepatitis C associated mixed cryoglobulinema AD 131:1185–1193, 1995; JAAD 34:219–223, 1996; livedo reticularis JAAD 37:659, 1997 HIV-1 acute infection - erythematous macules, morbilliform eruptions on trunk and face, also palms and soles with arthralgias JAAD 28:167–173, 1993; AD 134:1279–1284, 1998 Human bite Human herpesvirus 8 – relapsing inflammatory syndrome; fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, exanthem of hands, wrists, and elbows NEJM 353:156–163, 2005 Infectious mononucleosis Lassa fever (arenavirus) – morbilliform or petechial rash with conjunctivitis J Infect Dis 155:445–455, 1985 Leishmaniasis - dactylitis Lemierre’s syndrome (human necrobacillosis) – Fusobacterium necrophorum; suppurative thrombophlebitis of tonsillar and peritonsillar veins and internal jugular vein; oropharyngeal pain, neck swelling, pulmonary symptoms, arthralgias Clin Inf Dis 31:524–532, 2000 Leprosy – lepromatous leprosy JAMA Derm 153:313–314, 2017; polyarthritis, dactylitis with erythema nodosum leprosum JAAD

Arthritis and Rash (Polyarthritis and Monoarthritis) 51:416–426, 2004; AD 138:1607–1612, 2002; Rook p.1227, 1998, Sixth Edition; type 1 reaction demonstrates reappearance of resolved lesions, acute peripheral neuritis, edema of hands, feet, and face; type 2 reactions – erythema nodosum leprosum, with fever, malaise, arthritis, orchitis and/or glomerulonephritis; 70% of leprosy patients present with joint pain JAAD 83:17–30, 2020; JAAD 57:914–917, 2007; leprous dactylitis; new painful dermal or subcutaneous nodules with fever, anorexia, malaise, arthralgias and myalgias, epidydimitis, orchitis, periostitis, dactylitis, lymphadenitis, hepatosplenomegaly, glomerulonephritis, iridocyclitis, panniculitis, edema of dermis JAAD 71:795–803, 2014 Lyme disease - erythema migrans (erythema chronicum migrans); tick bite, red papule 3–32 days later, bright red outer borders, flat, raised; central clearing, indurated, vesicular, bullous, necrotic Clin Inf Dis 31:533–542, 2000; Secondary lesions - multiple recurrent annular, smaller, migrate less; lack indurated centers; Borrelial lymphocytoma (blue-red nodule of earlobe, scrotum, breast) - acrodermatitis chronica atrophicans, Arthritis; late manifestation, from several weeks to years later; intermittent, recurring in up to 40% of untreated patients Lymphogranuloma venereum JAAD 41:511–529, 1999 Mansonella perstans – pericardial inflammation, subcutaneous nodules, peritoneal or pleural cavity involvement, angioedema, pruritus, fever, headaches, arthralgias, neurologic symptoms JAAD 75:19–30, 2016 Melioidosis – Burkholderia pseudomallei; septic arthritis, abscesses, ulcers JAAD 75:1–16, 2016; Clin Inf Dis 31:981–986, 2000 Meningococcemia Ped Derm 13:483–487, 1996; chronic - fever and arthralgias Clin Exp Rheumatol 20:553–554, 2002; BJD 153:669– 671, 2005; Med J Aust 153:556–559, 1990 Moraxella osloensis – gonococcemia-like infection Cutis 21:657– 659, 1978 Mumps - adult males Murine typhus (Rickettsia typhi) – arthralgia MMWR 52:1224–1226, 2003 Mycetoma Mycobacterium abscessus – breast abscesses with tenosynovitis; erythema over joints associated with intramammary silicone breast implants with serum sickness-like syndrome JAAD 50:450–454, 2004 Mycobacterium haemophilum BJD 149:200–202, 2003; AD 138:229–230, 2002 Mycobacterium kansasii – swollen fingers JAAD 45:620–624, 2001 Mycobacterium marinum J Clin Microbiol 28:2570–2572, 1990; acute bursitis Dermatol Clin 33:509–630, 2015 Mycobacterium tuberculosis – multifocal scrofuloderma Ped Derm 22:440–443, 2005; lichen scrofulosorum – dactylitis Rook p.1200, 1998, Sixth Edition; yellow to red-brown flat-topped papules, slightly scaly, surmounted with minute pustule; trunk scrofulosorum Ped Derm 17:373–376, 2000; AD 124:1421–1426, 1988; Clin Exp Dermatol 1:391–394, 1976; lupus vulgaris; dactylitis; presenting as tophaceous gout J Rheumatol 16:700–702, 1989 Mycoplasma phocacerbrale – seal finger; swollen digit with drainage Clin Infect Dis 27:1168–1170, 1998; novel Mycoplasma species Clin Inf Dis 62:491–493, 2016 Mycotic aneurysm, femoral - arthritis and purpura Br J Rheumatol 24:364–366, 1985 Nocardia asteroides - personal observation Ockelbo disease - arthritis, exanthem - due to Sindbis-virus like agent Lancet Apr3;1 (8275);795–796, 1982

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Onchocerciasis Cutis 65:293–297, 2000 Parvovirus B19 (erythema infectiosum, fifth disease) JAAD 27:466, 1992; J Clin Inf Dis 21:1424–1430, 1995   Adults seldom have typical "slapped cheeks"  Papular-purpuric glove and socks syndrome Ped Derm 15:413, 1998   Macular, lacy or reticulate erythema on the extremities  Bullous papular-purpuric gloves and socks syndrome with oral aphthae of tongue JAAD 60:691–695, 2009  Pruritus, sometimes severe, with or without rash in a patient with acute onset arthritis   Sudden onset, symmetric polyarthritis, particularly of hands   Lupus-like presentation J Rheumatol 19:169–171, 1992 Pasteurella multocida – periocular abscess and cellulitis; tenosynovitis, septic arthritis Am J Ophthalmol 128:514–515, 1999; JAAD 33:1019–1029, 1995 Pine moth caterpillar disease – skin nodules and arthritis Skeletal Radiol 15:422–427, 1986 Pogost disease - alphavirus infection with rash and arthritis J Clin Lab Immunol 21:77–82, 1986 Rat bite fever (Streptococcus moniliformis) - fever, arthritis, exanthem; papules and papulopustules of face and hand; hand and foot swellings; eschar JAMA Derm 152:723–724, 2016; Clin Inf Dis 60:1388,1436–1437, 2015; Ped Derm 29:767–768, 2012; acral hemorrhagic pustules JAAD 38:330–332, 1998; septic arthritis; arthralgias AD 148:1411–1416, 2012; Clin Microbiol Rev 20:13–22, 2007; Clin Infect Dis 43:1586–1587,1616–1617, 2006; MMWR 53:1198–1202, 2005; Clin Orthop 380:173–176, 2000   Erythematous macules, papules 2–3 days after symptoms:    most marked on the extremities, particularly about joints;    measles-like, involves palms and soles   Fever, chills, headache, myalgias, arthritis after rat bite  healed  Haverhill fever - erythema arthriticum epidemicum ("Sodoku") Spirillium minus Relapsing fever (tick-borne relapsing fever) – Ornithodoros soft ticks transmitting Borrelia hermsii, B.turicata, or B. parkeri; 1–2cm rose-colored macules, papules, petechiae, purpura, facial flushing; arthralgias, iritis, myalgia JAAD 49:363–392, 2003; diffuse macular rash Rheumatic fever NEJM 369:75–80, 2013; JAAD 8:724–728, 1983   Abrupt onset polyarthritis, fever in adults   1/3 adults have no recollection of pharyngitis   Spreading erythematous rings (erythema marginatum)   Duration of rash - few hours; pattern changing hourly   Trunk and extremities  Carditis   Migratory arthritis   Dramatic response to salicylates Rickettsia parkeri rickettsiosis – Gulf coast tick (Amblyomma maculatum); eschar with surrounding petechiae, fever, fatigue, headache, myalgia, arthralgia, morbilliform or vesiculopapular rash of trunk and extremities, palms and soles, and occasionally the face; some lesions with small vesicle or pustule Clin Inf Dis 47:1188–1196, 2008 Rocky Mountain spotted fever Roseola – adults Rubella NEJM 369:558, 2013 Rubella vaccination - 1–2 days fever, respiratory symptoms, sub-occipital lymphadenopathy; generalized pink-red morbilliform rash lasting 3 1/2 days; additive symmetric polyarthritis with predilection young adult females

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Scarlet fever with septic arthritis – Streptococcus pyogenes; scarlatiniform (sandpaper) rash JAAD 39:383–398, 1998; JAAD 21:891–903, 1989 Scedosporium apiospermum – septic arthritis; periarticular erythema Clin Inf Dis 56:1778,1838–1839, 2013 Schistosomiasis (S. japonicum) - Katayama fever – purpura, arthralgia, systemic symptoms BJD 135:110–112, 1996; Dermatol Clin 7:291–300, 1989 Seal finger – painful, swollen red finger; synovitis J Rheumatol 13:647–648, 1986 Sporotrichosis JAAD 28:879–884, 1993; tenosynovitis J Rheumatol 16:550–553, 1989; bursitis Br J Rheumatol 37:461–462, 1998; prepatellar bursal sporotrichosis Clin Inf Dis 31:615–616, 2000 Subacute bacterial endocarditis – petechiae; proximal splinter hemorrhages, proximal; cryoglobulins causing purpura; leukocytoclatic vasculitis causing palpable purpura; Osler’s nodes - painful erythematous nodule with pale center; suddenly appears, usually on the fingertips; persists for hours to days; Janeway lesion - hemorrhagic and non-tender; may be nodular and commonly occurring on palms and soles JAAD 22:1088–1090, 1990 Syphilis - secondary Infect Dis Clin North Amer 1:83–85, 1987; congenital – osteochondritis – tibia and fibula at birth; later see osteomyelitis syphilitica (syphilitic dactylitis); Clutton’s joint – painless synovitis of the knees; sabre shins; Higoumenakis’ sign – sternoclavicular swelling in congenital syphilis; malignant lues Int J STDs and AIDS 23:599, 2012; Sex Trans Dis 36:512–514, 2009 Tick-borne relapsing fever – Ornithodoros (soft tick); Borrelia genus; high fever in irregular pattern, chills, headache, myalgia, arthralgia, fatigue, macular rash, conjunctival injection, hepatosplenomegaly, epistaxis, meningeal signs Cutis 82:38–46, 2008; Pediatr Drugs 7:163–176, 2005 Trench fever – red macules, 1cm or less; fever, malaise, chills, conjunctivitis, myalgias, arthralgias Clinics in Dermatol 28:483–488, 2010 Trypanosomiasis, African (Trypanosoma brucei rhodesiense) – joint pain during parasitemia; fever, headache, malaise; 3–10 days after appearance of chancre; ascites and peripheral edema JAAD 60:897–925, 2009; AD 131:1178–1182, 1995 Varicella - 1–5 large joints, may last up to 3 years J Clin Pathol 45:267–269, 1992 West Nile virus JAAD 51:820–823, 2004 Whipple’s disease (Tropheryma whipplei) – septal panniculitis associated with Whipple’s disease BJD 151:907–911, 2004; subcutaneous Whipple’s disease Clin Inf Dis 41:519–520,557–559, 2005; JAAD 16:188–190, 1987 Yaws – primary, secondary NEJM 372:693–695, 2015; Clin Dermatol 18:687–700, 2000; tertiary – hydrarthrosis JAAD 54:559–578, 2006; secondary yaws - osteitis, periostitis of long bones, polydactylitis of metacarpals, metatarsals Ped Derm 27:364–367, 2010; tertiary yaws - sabre shins; chronic arthritis in children; synovial inflammation and tendinous synovitis of elbows, knees, ankles Ped Derm 27:364–367, 2010 Yersiniosis Zika virus – fever, pinpoint red papules coalescing into morbilliform (macular and papular exanthem) eruption, arthralgia, palmar desquamation; conjunctivitis, myalgia, headache, retro-orbital pain, edema; palatal petechiae; microcephaly; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) MMWR 65:1161– 1165, 2016; JAAD 75:1–16, 2016; JAMA Derm 152:691–693, 2016; Clin Inf Dis 61:1445,1485–1486, 2015; NEJM 360:2536–2543, 2009

INFILTRATIVE DISEASES Amyloidosis – primary systemic; periarticular deposition of amyloid with decreased joint mobility Cutis 80:193–200, 2007; beta-2 microglobulin amyloidosis arthropathy – shoulder pain, carpal tunnel syndrome, flexor tendon deposits of hands, lichenoid papules, hyperpigmentation, subcutaneous nodules (amyloidomas); carpal tunnel syndrome JAMA Derm 151:564–565, 2015; Int J Exp Clin Inves 4:187–211, 1997 Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – limb contractures, sclerodermoid changes; gigantic lip fibromas, giant fibrous nodules of scalp and ears; giant nodules of frontal scalp and face; periarticular nodules of knees; gingival hypertrophy, bone deformities; mutation in gene encoding capillary morphogenesis protein 2 (ANTRX2 (CMG2)) Ped Derm 23:458–464, 2006; JAAD 55:1036–1043, 2006; Ped Derm 11:52–60, 1994; Pediatrics 87:228–234, 1991 Mastocytosis – arthralgias Scleromyxedema Dermatol Clin 20:493–501, 2002; JAAD 43:403– 408, 2000; JAAD 33:37–43, 1995; linear papules, leonine facies, arthritis and rash, sclerodermoid changes JAAD 44:273–281, 2001 Self-healing (papular) juvenile cutaneous mucinosis – arthralgias; skin colored nodules AD 148:755–760, 2012; JAAD 55:1036–1043, 2006; JAAD 50:S97–100, 2004; JAAD 44:273–281, 2001; Ped Derm 20:35–39, 2003; Dermatology 199:57–59, 1999; Ped Derm 14:460–462, 1997; AD 131:459–461, 1995; JAAD 11:327–332, 1984; Ann DV 107:51–57, 1980  Acute onset, polyarthritis, young age; rapid spontaneous resolution  Non-tender ivory white papules of the head, neck, trunk; periarticular   Deep nodules on face and periarticular regions   Hard periorbital edema, cheek bone areas

INFLAMMATORY DISEASES Ankylosing spondylitis – associated findings include psoriasis, anterior uveitis, inflammatory bowel disease, lung abnormalities, heart conduction defects, aortic insufficiency, renal abnormalities, osteoporosis, vertebral fractures Euro J Intern Med 22:554–560, 2011; Int J Rheumatol 2011:1–10 Aphthous stomatitis, recurrent Clin Exper Rheumatol 14:407–412, 1996 Chronic recurrent multifocal osteomyelitis (CRMO) – seen with varied neutrophilic dermatoses including SAPHO syndrome, pyoderma gangrenosum, acne fulminans, pustular psoriasis, Sweet’s syndrome JAAD 70:767–773, 2014; Ped Derm 26:497–505, 2009 Eosinophilic fasciitis – symmetric polyarthritis JAAD 49:1170–1174, 2003; AD 131:1329–1334, 1995 Erythema multiforme, Stevens-Johnson syndrome - polyarthritis Erythema nodosum Ann Rheum Dis 19:174–180, 1960; Lofgren’s syndrome – erythema nodosum with sarcoidosis and arthralgias Ped Derm 22:366–368, 2005 Febrile idiopathic lobar panniculitis of childhood – abdominal pain, arthralgia, fever, red nodules of face, legs, trunk, lipoatrophy Ped Derm 31:652, 2014 Hidradenitis suppurativa spondyloarthropathy Idiopathic granulomatous mastitis Ann DV 146:571, 2019; with erythema nodosum J Eur Acad DV 31:e391–393, 2017; arthritis Rheumatol Int 31:1093–1095, 2011

Arthritis and Rash (Polyarthritis and Monoarthritis) Interstitial granulomatous dermatitis with plaques (aka linear rheumatoid nodule, railway track dermatitis, linear granuloma annulare) – red, linear plaques with arthritis JAAD 46:892–899, 2002; linear erythematous cords JAAD 45:286–291, 2001; JAAD 34:957–961, 1996 Neutrophilic urticarial dermatosis – urticaria with polymorphonuclear leukocytes, joint inflammation; increased white blood cell count, increased C-reactive protein JAMA Derm 149:1244–1245, 2013; Medicine (Baltimore)88:23–31, 2009 Periostitis Annals Rheum Dis 64:1373–1374, 2005  Hypertrophic osteoarthropathy – distal diaphysis of long bones and metacarpal joints   Psoriatic onycho-pachydermo periostitis – terminal phalanx   Psoriatic arthritis – phalanges of fingers and toes   Reiter’s syndrome – phalanges of fingers and toes   Athletics – upper and lower extremities   Ossifying fasciitis – variable   Periostitis ossificans – variable   Polyarteritis nodosa – lower extremities   Systemic lupus erythematosus – variable   Facial infections – mandible, orbits   Florid reactive periostitis – phalanges of hands and feet   Osteoblastoma – variable  Bizarre parosteal osteochondromatous proliferation (Nora’s tumor) – hands and feet   Chondrosarcoma – variable   Interleukin-11 therapy – clavicle, long bones   Osteomyelitis – variable   Leg ulcers, chronic – tibia   SAPHO syndrome – variable Pruritic linear urticarial rash, fever, and systemic inflammatory disease of adolescents – urticaria, linear lesions, periorbital edema and erythema, and arthralgia Ped Derm 21:580–588, 2004 Pyoderma gangrenosum – association with rheumatoid arthritis, Behcet’s disease with polyarthritis; inflammatory bowel disease AD 125:57–64, 1989; pyoderma gangrenosum, palmoplantar pustulosis, and chronic recurrent multifocal osteomyelitis Ped Derm 15:435–438, 1998 Remitting seronegative symmetrical synovitis with pitting edema of hands BJD 174:1420–1421, 2016; AD 148:1217–1218, 2012; JAMA 254:2763–2767, 1985 Sarcoid – dactylitis and nail dystrophy; lupus pernio associated with sausage shaped digits; associated with chronic progressive fibrotic pulmonary disease, upper respiratory mucosal disease, bone cysts of the fingers, fusiform swelling of the digits; nasal ulceration, septal perforation JAAD 66:699–716, 2012; AD 111:362, 1975 Clinics in Chest Medicine 18:663–679, 1997; AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; juvenile sarcoid JAAD 48:S99–102, 2003 Ulcerative colitis, regional enteritis

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Cystic fibrosis-associated episodic arthritis – pink macules, urticarial papules, arthritis, purpura of legs, erythema nodosum, cutaneous vasculitis JAMA Derm 155:375–376, 2019; Respir Med 88:567–570, 1994; Am J Dis Child 143:1030–1032, 1989; Ann Rheum Dis 47:218–223, 1988; Arch Dis Child 59:377–379, 1984 Diabetes - neuropathy - Charcot joint; diabetic cheiropathy (stiff joints and waxy skin) NEJM 305:191–194, 1981 Gout Cutis 48:445–451, 1991; Ann Rheum Dis 29:461–468, 1970 Hemochromatosis – arthropathy JAMA 312:743–744, 2014; JAAD 51:205–211, 2004; Hum Molec Genet 9:2377–2382, 2000; Schweiz Med Wochenschr 122:842–849, 1992; AD 113:161–165, 1977; Medicine 34:381–430, 1955 Homocystinuria - joint dysplasia Hyperlipidemia   Type II hyperlipoproteinemia    Tendinous xanthomas or nodules    Achilles tendon, patella tendon, extensor tendons of hands and feet     Migratory polyarthritis that affects large joints     Acute episodes of Achilles tendonitis Mixed cryoglobulinemia Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) (scleromyxedema-like cutaneous fibrosing disorder) - associated with chronic renal failure with or without hemodialysis; patterned cobblestoned rippled red to violaceous thin fixed plaques with polygonal, reticular, or ameboid patterns; sclerodermoid changes; edema of fingers, wrists, toes, ankles; decreased range of motion; induced by gadolinium BJD 165:828–836, 2011; JAAD 61:868–874, 2009; AD 145:1164–1169, 2009; AD 145:183–187, 2009; BJD 158:1358–1362, 2008; JAAD 56:21–26, 2007; Semin Dialysis 19:191–194, 2006; JAAD 54:S31–34, 2006; Semin Arthritis Rheum 35:238–249, 2006; Semin Arthritis Rheum 35:208–210, 2006; Curr Opin Rheumatol 18:614–617, 2006; BJD 152:531–536, 2005; Arthritis Rheum 50:2660–2666, 2004; JAAD 48:55–60, 2003; JAAD 48:42–47, 2003; Am J Med 114:563–572, 2003; AD 139:903–906, 2003; Am J Dermatopathol 25:358, 2003; Am J Dermatopathol 23:383–393, 2001; Lancet 356:1000–1001, 2000 Ochronosis (alkaptonuria) - autosomal recessive; homogentisic acid dioxygenase deficiency JAAD 52:122–124, 2005; NEJM 347:2111– 2121, 2002; Am J Med 34:813–838, 1963   Diaper discoloration with alkaline soap   Brown-black cerumen, apocrine, eccrine sweat  Grey-blue discoloration of thin skin overlying pigmented cartilage, tendon; nose tip, extensor tendons, ears   Scleral discoloration   Onset of arthritis in 40s  Males>females   Shoulders, knees, hips  Spine    Calcified intervertebral discs    Lumbar pain, kyphosis, lordosis, sciatica

METABOLIC DISEASES

Olecranon bursitis in psoriasis - personal observation

Alpha-1 antitrypsin deficiency panniculitis – polyarthritis BJD 174:753–762, 2016

Oxalosis – primary hyperoxaluria JAAD 49:725–728, 2003; livedo and arthritis) AD 125:551–556, 1989; AD 116:213–214, 1980

Angiokeratoma corporis diffusum (Fabry’s disease (alpha galactosidase A) – X-linked recessive; arthritis of terminal phalanges JAAD 17:883–887, 1987; NEJM 276:1163–1167, 1967

Pancreatic panniculitis – periarticular subcutaneous nodules JAAD 45:325–361, 2001; JAAD 34:362–364, 1996; J Rheumatol 19:630– 632, 1992; Arthritis Rheum 22:547–553, 1979   Subcutaneous erythematous nodules   Often tender   Legs - posterior, lateral not tibial   Buttocks, trunk   Occasionally fluctuant

Complement deficiency - deficiency of beta subunit of the eighth component of complement - arthritis and exanthem Arthritis Fheum 37:1704–1706, 1994 Cryoglobulinemia JAAD 48:311–340, 2003

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  Spontaneous breakdown, drain creamy sterile material   Arthritis, periarthritis   Ankles, feet   Fat necrosis   Periarticular   Synovial membrane   Marrow cavity Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary aminopeptidase; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987 Scurvy - hemarthrosis or subperiosteal hemorrhage NEJM 374:1369–1374, 2016; Ped Derm 28:444–446, 2011; JAAD 41:895–906, 1999; NEJM 314:892–902, 1986

1991; Sezary syndrome and seronegative polyarthritis JAAD 48:220–226, 2003; angioimmunoblastic T-cell lymphoma (angioimmunoblastic lymphadenopathy with dysproteinemia) - morbilliform eruption; arthralgias, purpura, petechiae, urticaria, nodules JAAD 65:855–862, 2011; NEJM 361:900–911, 2009; BJD 144:878–884, 2001; JAAD 36:290–295, 1997; JAAD 1:227–32, 1979 Metastases - metastatic breast cancer presenting with fever, rash, and arthritis Cancer 75:1608–1611, 1995; acrometastases – initial presentation as diffuse ankle pain J Am Podiatr Med Assoc 84:625–627, 1994 Myelodysplastic syndrome - polyarthritis, mononeuritis multiplex, dermatitis Clin Exp Rheumatol 9:629–633, 1991 Nuchal fibroma – solitary subcutaneous mass of back of neck; multiple lesions associated with Gardner’s syndrome JAAD 66:959–965, 2012

PARANEOPLASTIC DISORDERS Pancreatic panniculitis - acinar cell carcinoma of pancreas; red nodules of legs; fever and arthritis Cutis 91:186–190, 2013 Paraneoplastic vasculitis J Rheumatol 18:721–727, 1991; in chronic myelogenous leukemia Am J Med 80:1027–1030, 1986

Sickle cell anemia – dactylitis with unequal growth of digits Sitosterolemia - arthritis and tuberous xanthomas J Lipid Research 33:945–955, 1992

PRIMARY CUTANEOUS DISEASES

Vitamin A intoxication – bone aches in children

Acne conglobata Ann Int Med 97:520–525, 1982

Waldenstrom’s hypergammaglobulinemic purpura

Acne fulminans JAAD 28:572–579, 1993; Clin Rheumatol 5:118–123, 1986

NEOPLASTIC DISEASES

Acrodermatitis continua of Hallopeau (variant of pustular psoriasis of fingers and toes

Angioimmunoblastic T-cell lymphoma (lymphadenopathy) - polyarthritis, rash, and lymphadenopathy Clin Rheumatol 17:148–151, 1998

Acute parapsoriasis (pityriasis lichenoides et varioliformis acuta) (Mucha-Habermann disease) AD 123:1335–1339, 1987; AD 118:478, 1982

Atrial myxoma – arthralgias; cutaneous findings include acral cyanosis, blue toes, red acral macules and papules, petechiae, splinter hemorrhages, livedo reticularis, ulcers, red-violet malar flush, Raynaud’s phenomenon, serpiginous and annular, violaceous blanching lesions JAAD 60:1–20, 2009

Ainhum

Fibromatosis JAAD 66:959–965, 2012

Cutis laxa – lax joints with hypermobility JAAD 46:161–183, 2002

Giant cell tumor of the tendon sheath – strong association with osteoarthritis; multilobulated single or multiple JAAD 43:892, 2000; nodules of the fingers J Dermatol 23:290–292, 1996; J Bone Joint Surg Am 66:76–94, 1984

Delayed pressure urticaria – arthralgia Cutis 79:41–49, 2007; JAAD 29:954–958, 1993

Inflammatory linear verrucous epidermal nevus (ILVEN) – arthritis typical of psoriatic arthritis (asymmetric large and small joints with dactylitis) but skin lesion unresponsive to methotrexate J Pediatr 138:602–604, 2001 Juvenile hyaline fibromatosis JAAD 18:881–883, 1987   Progressive and disabling   Gingival hypertrophy, stunted growth   Osteolytic defects   Flexion contractures of the joints Kikuchi’s disease – red macules, malar erythema, oral ulcers, photosensitivity, conjunctival injection, lymphadenopathy, fever, arthralgia JAAD 59:130–136, 2008; morbilliform eruption Ped Derm 24:459–460, 2007

Autosomal recessive congenital ichthyosis – ichthyosis, erythroderma, collodion baby, contractures of large joints, palmoplantar hyperlinearity, edema of fingers; CYP4F22 mutation BJD 176:1068– 1073m 2017

Erythema elevatum diutinum – arthralgias Cutis 67:381–384, 2001; Ped Derm 15:411–412, 1998; Cutis 93:124–126, 1994 Febrile ulceronecrotic Mucha- Habermann disease (pityriasis lichenoides et varioliformis acuta) J Rheumatol 16:387–389, 1989; crusted ulcerated red plaques; diarrhea, pulmonary involvement, abdominal pain, CNS symptoms, arthritis Ped Derm 29:53–58, 2012 Granuloma annulare - painful acral granuloma annulare AD 142:49–54, 2006 Ichthyosis en confetti – joint contractures JAMA Derm 151:64–69, 2015 Lamellar ichthyosis – limitation of joint movement, flexion contractures, digital sclerodactyly Ledderhose’s disease – hallux varus NEJM 369:2137, 2013

Leukemia - natural killer cell CD 56- large granular lymphocytic leukemia with pseudo-Felty syndrome – arthritis, leg ulcer associated with thigh telangiectasia JAAD 62:496–501, 2010

Lipoatrophia semicircularis – anterolateral thighs; band-like circular depression; lipoatrophy of ankles BJD 105:591–593, 1981; JAAD 39:879–881, 1998

Lymphoma, including cutaneous T cell lymphoma (CTCL) – rheumatoid arthritis-like JAAD 51:111–117, 2004; Ann Int Med 114:571,

Long thumbs - personal observation

Arthritis and Rash (Polyarthritis and Monoarthritis) Pachydermodactyly – digital fibromatosis; bilateral asymptomatic swelling of soft tissues surrounding the PIP joints of second and fourth fingers; benign fibromatosis of fingers of young men; thought to be trauma-related; large knuckles Ped Derm 34:719–720, 2017; Reumatologia 54:136–140, 2016; AD 148:925–928, 2012; Ped Derm 27:306–307, 2010; AD 144:1651–1656, 2008; Clin Rheumatol 26:962–964, 2007; Clin Exp Dermatol 28:674–675,2003; Ann DV 125:247–250, 1998; Ped Derm 13:288–291, 1996; BJD 133:433– 437, 1995; AD 111:524, 1975; Bull Soc Fr Dermatol Syphiligr 80:455–458, 1973 Pityriasis rubra pilaris JAAD 81:638–640, 2019; Arthr Rheum 42:1998–2001, 1999 Psoriasis – psoriatic arthritis – peripheral asymmetric oligoarthritis, distal interphalangeal arthritis, symmetrical rheumatoid arthritis-like polyarthritis, arthritis mutilans, spondylitis or sacroiliitis NEJM 376:957–970, 2017; Semin Arthritis Rheum 3:55–78, 1973; pustular palmoplantar – chronic recurrent multifocal osteomyelitis JAAD 12:927–930, 1985; Dermatologica 159:37–45, 1979; sternoclavicular hyperostosis (SAPPHO) J Bone Joint Surg Am 68:103–112, 1986 Psoriatic onycho-pachydermo-periostitis AD 132:176–180, 1996 Pustulosis acuta generalisata – pustular eruption of palms, trunk; scattered sterile pustules with red inflammatory haloes; arthropathy; post-streptococcal JAAD 58:1056–1058, 2008; Ped Derm 24:272– 276, 2007 Pustulosis palmaris plantaris JAAD 18:666–671, 1988 Scleredema of Buschke (pseudoscleroderma) – stiffness and restricted movement of joints JAAD 11:128–134, 1984

SYNDROMES Activated STING in Vascular and Pulmonary syndrome – autoinflammatory disease; butterfly telangiectatic facies; acral violaceous psoriasiform, papulosquamous and atrophic vasculitis of hands; nodules of face, nose, and ears; fingertip ulcers with necrosis; nail dystrophy; nasal septal perforation; interstitial lung disease with fibrosis; polyarthritis; myositis NEJM 371:507–518, 2014 Adams-Oliver syndrome - personal observation AHA syndrome (arthritis or arthralgia, hives, angioedema) Rheumatol Int 7:277–279, 1987 Albright’s hereditary osteodystrophy (pseudohypoparathyroidism) – osteoma cutis – brachymetaphalangism and brachydactyly; periarticular calcified or ossified nodules (ectopic ossification); short stocky build; round face; low flat nasal bridge; short neck, developmental delay, cataracts, hearing loss, seizures, poor dentition, basal ganglia calcification, osteomalacia, rickets, osteoporosis JAMA Derm 149:975–976, 2013; JAAD 15:353–356, 1986; AD 104:636– 642, 1971; Medicine 37:317–352, 1958 Anti-phospholipid antibody syndrome (anticardiolipin antibody syndrome) Arthritis Rheum 46:1019–1027, 2002Lupus 4Suppl1:S27–31, 1995 Apert’s syndrome Bannayan-Riley-Ruvalcaba syndrome – autosomal dominant, hyperextensible joints, macrocephaly, developmental delay, pseudopapilledema, pigmented macules of glans penis, hamartomatous growths including subcutaneous and visceral lipomas, gastrointestinal polyposis, capillary and combined malformations, café au lait macules, testicular enlargement, thyroiditis, pectus excavatum, scoliosis; PTEN mutation JAAD 56: JAAD 56:541–564, 2007 Bazex-Dupre-Christol-like syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis,

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hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Ped Derm 23:286–290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Behcet’s disease – asymmetric non-destructive polyarthritis knees>>ankles, elbows, wrists BJD 159:555–560, 2008; JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999; JAAD 36:689–696, 1997; Ped Derm 11:95–101, 1994; J Oral Pathol 7:347, 1978 Benign joint hypermobility syndrome – arthralgia, joint dislocation, hyperextensible skin, laxity of eyelids, normal skin texture and thickness (unlike Ehlers-Danlos syndrome) J Rheumatol 13:239– 243, 1986 Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; translucent skin-colored papules (non-caseating granulomas) of trunk and extremities with uveitis, synovitis, symmetric polyarthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints); uveitis, iritis, vitritis, closed-angle glaucoma; mutations in NOD2 (nucleotide-binding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) JAAD 68:834– 853, 2013; AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996; chromosome 16p12-q21 JAAD 49:299–302, 2003; Am J Hum Genet 76:217–221, 1998; Am J Hum Genet 59:1097–1107, 1996 Borrone dermatocardioskeletal syndrome – autosomal recessive or X-linked; gingival hypertrophy, coarse facies, late eruption of teeth, loss of teeth, thick skin, acne conglobata, osteolysis, large joint flexion contractures, short stature, brachydactyly, camptodactyly, mitral valve prolapse, congestive heart failure Ped Derm 18:534– 536, 2001 Buschke-Ollendorff syndrome – osteopoikilosis with connective tissue nevi; elastomas, collagenomas, dermatofibrosis lenticularis; LEMD3 mutation; joint stiffness BJD 144:890–893, 2001; JID 99:129–137, 1992 Camptodactyly – flexion deformity of PIP joint of one or more fingers; may be associated with inflammatory arthritis; Blau’s syndrome – familial camptodactyly, granulomatous arthritis, uveitis, red rash BJD 163:1102–1115, 2010; Am J Dis Child 147:842–848, 1993; Weaver syndrome – camptodactyly with unusual facies, hoarse low-pitched cry, hypertonia J Pediatr 84:547–552, 1974 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of lateral forehead, cold-induced pernio-like lesions of hands and feet, gynecomastia, wide spaced nipples, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, lymphadenopathy, splenomegaly, protuberant abdomen Ped Derm 33:602–614, 2016; BJD 170:215–217, 2014; JAAD 68:834–853, 2013; Ped Derm 28:538–541, 2011; JAAD 62:487–495, 2010 Cerebro-oculo-facial-skeletal syndrome – microcephaly, cataracts, microphthalmia, facial dysmorphism, arthrogryphosis JAAD 75:873–882, 2016; JAMA Derm 149:1414–1418, 2013

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1

Chromosome 6q deletion syndrome - joint laxity Hum Hered 27:242–246, 1977

Familial histiocytic dermatoarthritis syndrome - uveitis, destructive arthritis; papulonodular eruption Am J Med 54:793–800, 1973

Chronic infantile neurological cutaneous articular syndrome (CINCA) (neonatal onset multisystem inflammatory disorder (NOMID)) – urticarial rash at birth, unique deforming arthropathy – bulging knees (premature patellar and long bone ossification), uveitis, mental retardation, short stature Ped Derm 22:222–226, 2005; AD 136:431–433, 2000; Eur J Ped 156:624–626, 1997; J Pediatr 99:79–83, 1981; IOMID - infantile-onset multisystem inflammatory disease - arthropathy, rash, and central nervous system involvement AD 136:1487–1494, 2000

Familial Mediterranean fever – monoarthritis in 75% Medicine 77:268–297, 1998; AD 134:929–931, 1998; QJMed 75:607–616, 1990; autosomal recessive; erysipelas-like erythema - mutation in MEFV (pyrin/marenostrin) JAAD 42:791–795, 2000; AD 136:1487– 1494, 2000

Congenital fascial dystrophy (stiff skin syndrome) – hirsutism, limited joint mobility, localized areas of stony hard skin of buttocks and legs JAAD 21:943–950, 1989; restrictive dermopathy - autosomal recessive - joint contractures AD 134:577–579, 1998 Congenital myosclerosis – joint contractures secondary to muscle sclerosis BJD 163:1102–1115, 2010 Conradi’s disease (chondrodysplasia punctata) – stiff joints Hautarzt 30:590–594, 1979 Costello syndrome – hyperextensible fingers with limited joint mobility, warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi Am J Med Genet 117:42–48, 2003; Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977 Cutis laxa type II – autosomal recessive; facial dysmorphism with all the changes of wrinkly skin syndrome; pre and postnatal growth retardation, delayed motor development, delayed closure of large fontanelle, congenital hip dislocation, bone dysplasias, parallel strips of redundant skin of back Ped Derm 23:225–230, 2006; Ped Derm 21:167–170, 2004 Cutis marmorata telangiectatica congenita syndrome – body asymmetry, 2–3 toe syndactyly, hypotonia, developmental delay, midfacial vascular stains, joint laxity, loose skin Ped Derm 24:555– 556, 2007 Congenital contractural arachnodactyly – due to tendon shortening; joint contractures, frontal bossing, and kyphoscoliosis BJD 163:1102–1115, 2010 Cryopyrin-associated periodic syndrome (CAPS) – urticarial-like eruptions, fever, distal arthralgia, neurologic symptoms, eye disease, amyloidosis JAAD 68:834–853, 2013 Distal arthrogryposis syndromes – joint contractures BJD 163:1102–1115, 2010 Ehlers-Danlos syndrome - joint hypermobility and laxity; soft velvety skin hyperextensible skin; thin translucent skin; tenascin-X deficiency BJD 163:1340–1345, 2010; type VI – blue sclerae, scleral fragility, joint hypermobility, pes planus (flat feet); osteoarthritis at age 30–40; skin hyperextensibility, easy bruising, thinned atrophic scarring, pseudotumors, marfanoid habitus, scoliosis, neonatal hypotonia, arterial dissection; varicose veins Cutis 82:242–248, 2008 Familial cold autoinflammatory syndrome (cold urticaria) – nonpruritic urticarial rash precipitated by cold; conjunctivitis, arthralgias of knees and ankles and arthritis; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin); CIAS1 Ped Derm 24:85–89, 2007; AD 142:1591–1597, 2006; JAAD 54:319– 321, 2006; BJD 150:1029–1031, 2004; JAMA 114:1067–1068, 1940 Familial dysautonomia (Riley-Day syndrome) (hereditary sensory and autonomic neuropathy type III) – Charcot joints BMJ iv:277– 278, 1967

Familial milia and absent dermatoglyphics – digital flexion contractures, webbed toes, palmoplantar hypohidrosis, painful fissured calluses, acral blistering, simian crease JAAD 59:1050–1063, 2008 Familial partial lipodystrophy, mandibuloacral dysplasia variety – autosomal recessive; short stature, high pitched voice, mandibular and clavicular hypoplasia, dental anomalies, acro-osteolysis, stiff joints, cutaneous atrophy, alopecia, nail dysplasia Am J Med 108:143–152, 2000 Farber’s disease (lipogranulomatosis) - deformed or stiff joints and periarticular subcutaneous nodules; coarse facial features Ped Derm 21:154–159, 2004; Eur J Ped 157:515–516, 1998; AD 130:1350–1354, 1994 Fibroblastic rheumatism – symmetrical polyarthritis, nodules over joints and on palms, elbows, knees, ears, neck, Raynaud’s phenomenon, sclerodactyly; joint contractures, thick palmar fascia; scalp nodules, red tender swelling of toe tips, periarticular nodule; skin lesions resolve spontaneously Cutis 100:354, 356–357, 2017; JAAD 66:959–965, 2012; JAAD 55:1036–143, 2006; AD 139:657– 662, 2003; Ped Derm 19:532–535, 2002; AD 139:657–662, 2003; AD 131:710–712, 1995; Clin Exp Dermatol 19:268–270, 1994; AD 131:710–712, 1995; Clin Exp Dermatol 19:268–270, 1994; JAAD 14:1086–1088, 1986; Rev Rheum Ed Fr 47:345–351, 1980; periungual papules Ped Derm 19:532–535, 2002 Francois syndrome GEMSS syndrome - autosomal dominant; glaucoma, lens ectopia, microspherophakia, stiff joints, shortness, gingival hypertrophy, flexion contractures of joints, osteolytic defects, stunted growth, stocky pseudoathletic build, sclerosis of upper back and extremities AD 131:1170–1174, 1995 Generalized progressive fibromatosis – contractures of hands, shoulders, knees JAAD 55:S32–37, 2006 Geroderma osteodysplastica (Bamatter syndrome) (osteodysplastic geroderma) – autosomal recessive; short stature, cutis laxa-like changes with drooping eyelids and jowls (characteristic facies with hypoplastic midface), osteoporosis and skeletal abnormalities; lax wrinkled, atrophic skin, joint hyperextensibility, growth retardation Ped Derm 23:467–472, 2006; Ped Derm 16:113–117, 1999; Am J Med Genet 3:389–395, 1979; Hum Genet 40:311–324, 1978 Haim-Munk syndrome – autosomal recessive; palmoplantar keratoderma, periodontitis, psoriasiform plaques of palms and soles, onychogryphosis, arachnodactyly, acro-osteolysis, flexion contractures; mutation of lysosomal protease cathepsin C JAAD 58:339–344, 2008; pes planus BJD 77:42–54, 1965 Hand-heart syndrome (Holt-Oram syndrome) - personal observation Hemophagocytic lymphohistiocytosis syndrome – fever, pancytopenia, lymphadenopathy, hepatomegaly, splenomegaly, neurologic, joint, purpura, morbilliform eruption, kidney, and cardiac involvement, central nervous system dysfunction Eur Rev Med Pharmacol Sci, 16:1414–1424, 2012; Genes Immunol 13:289–298, 2012   Familial HLH – known genetic defects (perforin)   Immune deficiencies   Chediak-Higash syndrome   Griscelli syndrome    X-linked lymphoproliferative syndrome  Acquired   Infections

Arthritis and Rash (Polyarthritis and Monoarthritis)   Endogenous products   Rheumatic diseases   Neoplasms Hereditary angioedema – autosomal dominant; joint swelling; serpiginous erythema; triad of circumscribed edema of the skin, laryngeal edema, and abdominal pain BJD 161:1153–1158, 2009; Sybert’s Genetic Skin Disorders; Hosp TID No.40.1 rk 4:741–747, 1886; Monatsschr Prakt Dermatol 1:129–131, 1882; C’1 INH deficiency NEJM 359:1027–1036, 2008; J Allergy Clin Immunol 106:546–550, 2000; Lancet 356:213–217, 2000; NEJM 334:1666–1667, 1996; Medicine 71:206–215, 1992; Am J Med 35:37–44, 1963; Am J Med Si 95:362–367, 1888; type III - normal C1 INH activity in women with relationship to estrogenic activity JAAD 53:373–388, 2005; BJD 150:157–158, 2004; type III in men and women BJD 154:542–545, 2006 Huriez syndrome – autosomal dominant; palmoplantar keratoderma with sclerodactyly and scleroatrophy of distal extremities with nail changes (hypoplasia, longitudinal ridging, distal splitting); hypohidrosis, poikilodermatous changes of nose, flexion contractures of fingers AD 146:1419–1424, 2010; TIG 13:229, 1997 Hystrix-like keratosis with nail and joint involvement Dermatology 192:321–324, 1996 Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked recessive; hyperextensible joints; atopic dermatitis; collodion membrane and erythema at birth; ichthyosis, spiny (keratotic) follicular papules (generalized follicular keratoses), non-scarring alopecia totalis, keratotic papules of elbows, knees, fingers, Achilles tendons; extensor surfaces, xerosis; punctate keratitis, photophobia with progressive corneal scarring; nail dystrophy, paronychia, psychomotor delay, short stature; enamel dysplasia, beefy red tongue and gingiva, angular stomatitis (angular cheilitis), lamellar scales, psoriasiform plaques, palmoplantar erythema; mutation of MBTPS2 (intramembrane zinc metalloproteinase needed for cholesterol homeostasis and endoplasmic reticulum stress response) JAAD 64:716–722, 2011; Ped Derm 26:427–431, 2009; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; AD 125:103–106, 1989; Ped Derm 12:195, 1995; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999; BJD 21:165–189, 1909 Infantile restrictive dermopathy – autosomal recessive; taut shiny skin with flexion of joints Eur J Ped 155:987–989, 1996; Am J Med Genet 24:631–648, 1986 Juvenile hyaline fibromatosis (infantile systemic hyalinosis) (Murray-Puretic-Drescher syndrome) – autosomal recessive; gingival fibromatosis with hypertrophy, focal skin nodularity with multiple subcutaneous tumors (nodular perianal lesions, facial red or pearly papules (paranasal, periauricular), dusky red plaques of buttocks, ears, lips), synophrys, thickened skin with sclerodermiform atrophy, osteolytic (osteoporotic) skeletal lesions, stiff muscles with massive stiffness, flexural joint contractures (frog leg position), hyperpigmentation, flexion contractures of joints, juxta-articular nodules (knuckle pads), nodules of ears, diarrhea, recurrent suppurative infections failure to thrive with stunted growth (growth failure) and death in infancy; CMG2 (capillary morphogenesis protein 2) (transmembrane protein); deposition of collagen type VI (bound to laminin and collagen 4) mutation (chromosome 4q21) JAAD 61:629–638, 2009; Ped Derm 25:557–558, 2008; JAAD 58:303–307, 2008; Ped Derm 21:154–159, 2004; JAAD 50:S61–64, 2004; Ped Derm 18:534–536, 2001; Ped Derm 18:400–402, 2001; Dermatology 198:18–25, 1999; Int J Paediatr Dent 6:39–43, 1996; J Periodontol 67:451–453, 1996; Dermatology 190:148–151, 1995; Ped Derm 11:52–60, 1994; Ped Derm 6:68–75, 1989; Oral Surg 63:71–77, 1987; Arch Fr Pediatr 35:1063–1074, 1978; nodular perianal lesions, ears, lips, gingival hypertrophy, hyperpigmentation;

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mutation of capillary morphogenesis protein 2 gene BJD 157:1037– 1039, 2007; AD 112:86–88, 1976 Kabuki makeup syndrome (Niikawa-Kuroki syndrome) – short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly; preauricular dimple/fistula Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 570–573, 1981 Kawasaki’s disease- arthralgias, especially in adults JAAD 69:501–510, 2013 Kindler’s syndrome – joint laxity AD 140:939–944, 2004 Laband syndrome (Zimmermann-Laband syndrome) – gingival fibromatosis, aplasia or dysplasia of fingernails, hypertrophy of nasal tip and ears, hypermobility, limb asymmetry Am J Med Genet 31:691–695, 1988; Am J Med Genet 25:543–548, 1986 Loeys-Dietz syndrome – joint hypermobility, thin skin with prominent veins, marfanoid body habitus, triangular delicate face, hypertelorism, bifid uvula or cleft palate, arterial dissection and rupture, prominent eyes, blue sclerae, aortic aneurysms, generalized arterial tortuosity; type I and II TGF beta receptor JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005 MAGIC syndrome – mouth and genital ulcers with inflamed cartilage Majeed syndrome – autosomal recessive; chronic recurrent multifocal osteomyelitis; congenital dyserythropoietic anemia, periodic fevers; Sweet’s syndrome; chronic pustulosis; mutation in LPIN2 J Clin Immunol 28 (Suppl 1)S73–83, 2008; J Med Genet 4:551–557, 2005; Eur J Pediatr 160:705–710, 2001 Marfan’s syndrome – joint hypermobility, tight joints with contractures JAAD 46:161–183, 2002; Int J Dermatol 28:291–299, 1989 Marfanoid hypermobility syndrome – marked joint hypermobility, cutaneous hyperextensibility, aortic dissection, no easy bruising JAAD 55:S41–45, 2006 McCune-Albright’s syndrome (polyostotic fibrous dysplasia) Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome – macrocephaly, face and limb asymmetry, craniofacial abnormalities, joint laxity or soft skin, distal limb malformation; developmental delay Ped Derm 30:541–548, 2013; Nat Genet 44:934–940, 2012 Michelin tire baby syndrome – either nevus lipomatosis or diffuse smooth muscle hamartoma; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques; mental retardation, tendinous hyperlaxity, seizures, mastocytosis, complex malformations syndrome (bilateral calcaneovalgus deformity, cleft palate, inguinal hernia, hip deformity, clefting of lateral mouth commissures, shawl scrotum, absent foreskin Ped Derm 24:628–231, 2007; Ped Derm 22:245–249, 2005; BJD 129:60–68,1993; JAAD 28:364–370, 1993; Ped Derm 6:329–331, 1989; diffuse lipomatous hypertrophy AD 100:320–323, 1969 Moore-Federman syndrome - short stature, stiffness of joints, characteristic facies J Med Gen 26:320–325, 1989

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Muckle-Wells syndrome – autosomal dominant; macular erythema (evanescent red macules), urticaria (cold air urticaria), deafness, extremity pain, arthralgias of knees and ankles with arthritis; nephropathy, AA amyloidosis with neuropathy; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin) SkinMed 11:80–83, 2013; AD 142:1591–1597, 2006; BJD 151:99– 104, 2004; JAAD 39:290–291, 1998; BJD 100:87–92, 1979; QJMed 31:235–248, 1962 Multicentric reticulohistiocytosis (reticulohistiocytoma cutis – destructive arthritis with rheumatoid-like nodules); periarticular brown papulonodules of face and hands, periungual coral beads; mucosal lesions; xanthelasma; rapidly destructive arthritis mutilans JAAD 56:302–316, 2007; JAAD 53:1075–1079, 2005; Clin Exp Rheumatol 23:97–99, 2005; AD 140:919–921, 2004; Clin Exp Dermatol 15:1–6, 1990; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968 Nail patella syndrome – hyperextensible joints; absence of distal interphalangeal creases; webbing between digits Ped Derm 27:93–94, 2010; Dermatology 213:153–155, 2006NERDS - nodules, eosinophilia, rheumatism, dermatitis, and swelling Dermatology 191:133–138, 1995 Neutrophilic urticarial (neutrophilic urticarial with systemic inflammation) – urticaria, night sweats, fever, polyarticular arthritis; increased IL-1; treated with anakinra AD 149:453–458, 2013 NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic self-limiting fever, polyarthritis, polyarthralgia, red plaques of face and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – urticarial lesions, chronic meningitis, arthralgias of knees and ankles with deforming arthropathy with epiphyseal bone formation, deafness, hepatosplenomegaly, uveitis, vitreitis, papilledema, corneal stromal keratopathy; mental retardation; fever and rash more severe in evening; mutation in NLRP3 (CIAS 1) which encodes cryopyrin AD 144:392–402, 2008; AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319– 321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005; Noonan’s syndrome – malformed ears, nevi, keloids, transient lymphedema, ulerythema ophyrogenes, keratosis follicularis spinulosa decalvans, joint hyperextensibility, hypertelorism, webbed neck, down slanting of palpebral fissures, keratosis pilaris atrophicans, short stature, chest deformity (pectus carinatum and pectus excavatum), cubitus valgus, radioulnar synostosis, clino-brachydactyly, congenital heart disease; PTPN 11 gene on chromosome 12; gain of function of non-receptor protein tyrosine phosphate SHP-2 or KRAS gene Ped Derm 24:417–418, 2007; JAAD 46:161–183, 2002; J Med Genet 24:9–13, 1987; J Pediatr 63:468–470, 1963 Novel fibrosing disorder – subcutaneous fibrotic nodules, progressive distal joint contractures, marfanoid stature, forehead nodules, skin tightening (sclerodermoid changes), palmoplantar nodules, nodules of elbows and knees, linear arrays of nodules later in course; differentiate from Marfan’s syndrome, congenital contractural arachnodactyly, Winchester syndrome, multicentric osteolysis nodulosis and arthropathy (MONA) syndrome BJD 163:1102–1115, 2010 Oligodontia, keratitis, skin ulceration, and arthroosteolysis Am J Med Genet 15:205–210, 1983 Osteogenesis imperfecta Pachydermodactyly - swollen fingers (fibromatosis) JAAD 38:359– 362, 1998

Pachydermoperiostosis JAAD 38:359–362, 1998   Spade-like enlargement of hands and feet   Warmth of fingertips, paronychia   Excessive sweating of hands and feet   Coarsening facial features mimicking acromegaly    Leonine facies, worried or angry look    Cutis verticis gyrata   Palmar plantar keratoderma   Greasiness to skin   Clubbing + periostitis + acromegalic features   Asymptomatic periosteal reaction   Mild arthralgia  Severe deep-seated aching or burning pain, aggravated by dependency   Tenderness over distal long bones   Insidious onset, mild rheumatic complaints   Idiopathic, suppurative pulmonary disease   Rapidly progressive, prominent joint pain   Malignant disease Palmar fasciitis and polyarthritis syndrome – painful swelling over palmar PIP joints – indurated palmar skin; flexion contractures; may be paraneoplastic (transitional cell carcinoma of the bladder) JAAD 64:1159–1163, 2011; Ann Int Med 96:424–431, 1982 PAM1 (PSTPIP1-associated myeloid related proteinemia) – autoinflammatory syndrome – acne vulgaris, pyoderma gangrenosum, thrombocytopenia, anemia, sterile osteomyelitis, sterile arthritis BJD 179:982–983, 2018 PAPA (pyogenic arthritis with pyoderma gangrenosum) syndrome – pyoderma gangrenosum, cystic acne, acne fulminans, non-axial destructive aseptic arthritis; sterile abscesses at injection sites; attacks last 5 days; mutation in CD2 binding protein-1 Ped Derm 22:262–265, 2005; Proc Natl Acad Sci USA 100:13501–13506, 2003; Mayo Clin Proc 72:611–615, 1997 PAPASH syndrome – pyogenic arthritis, pyoderma gangrenosum, acne, hidradenitis suppurativa; autoinflammatory syndrome; mutation in PSTPIP1 gene JAMA Derm 149:762–764, 2013 Parana hard skin syndrome – frozen joints secondary to skin tightening BJD 163:1102–1115, 2010 Partial lipodystrophy, complement abnormalities, vasculitis – macroglossia, polyarthralgia, mononeuritis, hypertrophy of subcutaneous tissue Ann DV 114:1083–1091, 1987 Periodic fever BJD 151:99–104, 2004 POEMS syndrome (Crow-Fukasi syndrome, Takatsuki syndrome) – plethora, angiomas (cherry, globular, glomeruloid) presenting as rd nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, scleroderma-­like changes, hyperhidrosis, clubbing, leukonychia, polyneuropathy, papilledema, sclerotic bone lesions, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss, fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias JAAD 55:149–152, 2006; – bilateral Charcot joints Dtsch Med Wochenschr 124:346–350, 1999 Progeria (Hutchinson-Guilford syndrome) AD 125:540–544, 1989 Progressive osseous heteroplasia – ankylosis, contractures, growth retardation Proteus syndrome – skeletal overgrowth of arms and legs limiting joint mobility AD 140:947–953, 2004 Pseudoacromegaly – autosomal recessive; skin ulcers, arthro-osteolysis, keratitis, oligodontia Am J Med Genet 15:205–210, 1983 PYCR1-related cutis laxa – hair loss, prominent scalp veins, triangular shaped face, microcephaly, short stature, hypermobility of joints, thin atrophic skin, wrinkled skin, muscle weakness, finger contractures Dtsch Arztebl Intl 16:489–496, 2019

Arthritis and Rash (Polyarthritis and Monoarthritis) Pyogenic sterile arthritis, pyoderma gangrenosum, and acne – autosomal dominant; mutation in proline-serine-­threonine phosphatase interacting protein-1 (CD2-binding protein 1) JAAD 70:767–773, 2014 Reflex sympathetic dystrophy (complex regional pain syndrome) – limited joint mobility Cutis 68:179–182, 2001 Reactive arthritis JAAD 59:113–121, 2008   Circinate balanitis – annular or serpiginous   Asymptomatic oral mucosal erosions   Keratoderma blennorrhagica   Pustular psoriasis   Psoriasiform plaques   Nail changes   Geographic tongue   Aortic insufficiency   Cardiac conduction abnormalities   Conjunctivitis, uveitis, keratitis – sterile mucopurulent discharge   IgA nephropathy  Myelopathy   Palatal erosions, oral ulcers, glossitis  Seronegative non-suppurative arthritis – polyarticular knees, ankles, metatarsophalangeal, sacroiliac joints; relative sparing of hands and wrists; occasionally monoarticular; enthesitis  Spondylitis   Achilles tendonitis   Plantar fasciitis   Sausage digits – dactylitis  Urethritis   Ulcerative vulvitis – red crusted plaques of vulva and perineum Relapsing polychondritis – may mimic rheumatoid arthritis Clin Rheumatol 6:453–457, 1987; Medicine 55:193–216, 1976 REM syndrome (reticular erythematous mucinosis syndrome) Acta DV 66:442–445, 1986 Rosai-Dorfman syndrome Am J Clin Pathol 82:515–525, 1984 SAPHO syndrome - palmoplantar pustulosis with sternoclavicular hyperostosis; acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis Cutis 71:63–67, 2003; Cutis 64:253–258, 1999; Cutis 62:75–76, 1998; Ann Rheum Dis 56:52–58, 1997: AD 128:699–700, 1992; JAAD 18:666–671, 1988; Rev Rheum Mal Osteoarthritic 54:187–196, 1987; Clin Rheumatol 5:118–123, 1986; Ann Rev Rheum Dis 40:547–553, 1981 Scheie syndrome (mucopolysaccaridosis type I) – autosomal recessive; alpha-l-iduronate deficiency; disorder of glycosaminoglycans; corneal clouding, joint stiffness, cardiac valvular disease Ped Derm 33:594–601, 2016 Schnitzler’s syndrome - chronic urticaria, intermittent fever, and IgM monoclonal gammopathy (macroglobulinemia), high ESR, leukocytosis, arthralgia, arthritis, with disabling bone pain (osteosclerotic) of distal femur and proximal tibia, palpable lymphadenopathy, hepatosplenomegaly AD 143:1046–1050, 2007; JAAD 56:S120– 122, 2007; J Eur Acad Dermatol Venereol 16:267–270, 2007; BJD 142:954–959, 2000; JAAD 30:316–318, 1994; AD 130:1193–1198, 1994; JAAD 20:855–857, 1989; JAAD 20:206–211, 1989 Schopf-Schulz-Passarge syndrome Schwartz-Jampel syndrome (Stuve-Wiedemann syndrome) – autosomal recessive; primary skeletal dysplasia; joint restrictions; hyperthermic episodes, dysautonomia, respiratory and feeding difficulties, early mortality, eruptive vellus hair cysts and clefted tongue Ped Derm 37:381–382, 2020 SHORT syndrome – short stature, hyperextensible joints, ocular depression, Reiger (ocular and dental) anomaly, teething delay, loss of subcutaneous fat of face, upper extremities, chest and

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Sjogren’s syndrome Soto’s syndrome – joint hyperextensibility; cutis laxa; cerebral gigantism J Med Genet 36:51–56, 1999 Stiff skin syndrome – sclerodermoid changes of pelvic or shoulder girdle, limited joint mobility, mild overlying hypertrichosis, especially over lumbosacral area JAAD 75:163–168, 2016; AD 144:1351– 1359, 2008; Ped Derm 20:339–341, 2003; Ped Derm 19:67–72, 2002; Ped Derm 2:87–97, 1984; Pediatrics 47:360–369, 1971 Still’s disease – adult onset juvenile rheumatoid arthritis Sweet’s syndrome JAAD 23:494–498, 1990; Arthritis Rheum 18:35–41, 1975; BJD 76:349–356, 1964; including drug-induced Sweet’s syndrome - red plaques, nasal ulcers, perianal ulcers celecoxib, G-CSF, all-trans retinoic acid JAAD 45:300–302, 2001; Sweet’s syndrome in children – arthritis, arthralgia, tibial pain, osteomyelitis Ped Derm 26:452–457, 2009 Synovitis of the wrists, carpal joints, and fingers with pain swelling and pitting edema (boxing glove hand) or feet Clin Exp Rheumatol 18:553–555, 2000 Systemic-onset juvenile idiopathic arthritis – spiking fevers, daily evanescent morbilliform eruption, polyarticular arthritis JAAD 68:834–853, 2013 Trichorhinophalangeal syndrome type I – autosomal dominant; slow growing short blond hair, receding frontotemporal hairline with high bossed forehead; thin nails, koilonychias, leukonychia, facial pallor, pear-shaped nose with bulbous nose tip, wide long philtrum, thin upper lip, triangular face, receding chin, tubercle of normal skin below the lower lip, protruding ears, distension and deviation with fusiform swelling of the PIP joints; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, lateral eyebrows sparse and brittle,, dense medially, bone deformities (hands short and stubby), joint hyperextensibility, cone-shaped epiphyses of bones of hand, lateral deviation of interphalangeal joints, flat feet, hip malformations, high arched palate, supernumerary teeth, dental malocclusion, mild short stature; hypotonia, hoarse deep voice, recurrent respiratory infections, hypoglycemia, diabetes mellitus, hypothyroidism, decreased growth hormone, renal and cardiac defects, mutation in zinc finger nuclear transcription factor (TRPS1 gene) Cutis 89:56,73–74, 2012; Ped Derm 26:171–175, 2009; Ped Derm 25:557–558, 2008; BJD 157:1021–1024, 2007; AD 137:1429– 1434, 2001; JAAD 31:331–336, 1994; Hum Genet 74:188–189, 1986; Helv Paediatr Acta 21:475–482, 1966 Trichorhinophalangeal syndrome type II – joint laxity, microcephaly, deep set eyes, exotropia, broad nasal bridge, thick ala nasi, foot deformities BJD 157:1021–1024, 2007; J Ped Orthop 6:133–138, 1986 Tuberous sclerosis – pseudocysts of the phalanges Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) - erythematous patches, tender red plaques, fever, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia with limitation of joint movement, abdominal pain, headache; Irish and Scottish predominance; mutation in TNFRSF1A - gene encoding 55kDa TNF receptor AD 136:1487–1494, 2000; Mayo Clin Proc 72:806–817, 1997 Weill-Marchesani syndrome Wells’ syndrome (eosinophilic cellulitis) JAAD 52:187–189, 2005; Trans St. Johns Hosp Dermatol Soc 57:46–56, 1971 Werner’s syndrome

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Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – autosomal recessive; present at birth, generalized lipoatrophy, macrocephaly, sparse hair, premature aging, wide open sutures, aged and triangular face with hypoplasia of facial bones, persistent fontanelles, prominent scalp veins, growth retardation, low set ears, beak shaped nose, neonatal teeth, slender limbs, large hands and feet with long fingers, joint contractures, large penis, pseudohydrocephalus, psychomotor retardation Ped Derm 22:75–78, 2005; J Med Genet 34:433–437, 1997; Am J Med Genet 35:91–94, 1990; Eur J Pediatr 130:65–70, 1979; Eur J Pediatr 124:101–111, 1977 Winchester syndrome – autosomal recessive; systemic hyalinosis with joint contractures JAAD 55:1036–1043, 2006; JAAD 50:S53– 56, 2004   Coarse facies   Dwarfism, corneal opacities   Osteoporosis, osteolysis   Rheumatoid-like joint destruction (carpal-tarsal osteolysis)   Gingival hypertrophy Ped Derm 23:458–464, 2006  Hyperpigmentation (patches of thickened hyperpigmented and hypertrichotic skin)  Hypertrichosis (patches of thickened hyperpigmented and hypertrichotic skin)  Thickening of the skin (patches of thickened hyperpigmented and hypertrichotic skin)  Widespread nodular lesions J Med Genet 26:772–775, 1989; Am J Med Genet 26:123–131, 1987; J Pediatr 84:701–709, 1974; Pediatrics 47:360–369, 1971 Wrinkly skin syndrome - autosomal recessive Clin Genet 38:307– 313, 1990; same as cutis laxa with growth and developmental delay; increased palmoplantar creases, prominent venous pattern over chest, mental retardation, microcephaly, hypotonia (joint laxity), musculoskeletal (decreased muscle mass, hip dislocation, winging of scapulae, vertebral deformities), short stature, craniofacial abnormalities, and connective tissue abnormalities Ped Derm 23:225–230, 2006; Am J Med Genet 101:213–220, 2001; Ped Derm 6:113–117, 1999; Am J Med Genet 85:194, 1999; Clin Genet 4:186–192, 1973

TOXINS Eosinophilia myalgia syndrome (l-tryptophan related) – arthralgia Int J Dermatol 31:223–228, 1992; Mayo Clin Proc 66:457–463, 1991; Ann Int Med 112:758–762, 1990 Hypervitaminosis A – bone pain Arch Intern Med 112:462–466, 1963 Polychlorinated biphenyl poisoning – chloracne, goiter, arthritis, and anemia Environ Health Perspect 107:715–719, 1999 Selenium toxicity – transverse white nail bands; exfoliative scalp dermatitis with hair loss, dizziness, fatigue, amenorrhea, nausea and vomiting, joint pain; ”Total Body Formula” dietary supplement JAAD 63:168–169, 2010

TRAUMA Familial cold urticaria - autosomal dominant AD 129:343–346, 1993 Pachydermodactyly due to obsessive compulsive behavior AD 130:387, 1994   vs. spina ventosa, osteitis multiplex cystoides Jungling, true knuckle pads, tuberous sclerosis

VASCULAR Acute hemorrhagic edema of infancy- personal observation Eosinophilic granulomatosis with polyangiitis - arthralgia BJD 127:199–204, 1992 Granulomatosis with polyangiitis presenting as reactive arthritis and synovitis - personal observation; breast necrosis, livedo reticularis, arthralgias Rev Med Brux 33:112–115, 2012; Br Med J ii:265–270, 1958 Henoch-Schonlein purpura JAAD 48:311–340, 2003; Ped Derm 15:357–359, 1998; Ped Derm 12:314–317, 1995; Am J Dis Child 99:833–854, 1960 Lymphatic malformations – knee arthropathy due to recurrent bleeding in subsynovial vascular plexus within the knee joint JAAD 65:893–906, 2011 Lymphostasis verrucosa cutis (chronic lymphedema, multiple causes) – brawny edema with impaired small joint mobility Macrocephaly-cutis marmorata telangiectatica congenita, macrocephalic neonatal hypotonia; midline facial nevus flammeus, congenital macrocephaly, macrosomia, segmental overgrowth, central nervous system malformations (hydrocephalus), connective tissue abnormalities, skin and joint hypermobility, toe syndactyly, frontal bossing, mental retardation JAAD 56:541–564, 2007 Multifocal lymphangioendotheliomatosis with thrombocytopenia – congenital appearance of hundreds of flat vascular papules and plaques associated with gastrointestinal bleeding, thrombocytopenia with bone and joint involvement; spontaneous resolution; flat or indurated red-brown or burgundy papules, plaques, nodules, and tumors; involvement of gastrointestinal tract, lungs, brain, spleen, synovium, muscle BJD 171:474–484, 2014; JAAD 67:898–903, 2012;J Pediatr Orthop 24:87–91, 2004 Polyarteritis nodosa, systemic or cutaneous Ped Derm 15:103–107, 1998; Ann Rheum Dis 54:134–136, 1995; cutaneous (livedo with nodules) – arthritis; arthralgias; painful or asymptomatic red or skin colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk; leg ulcers, atrophie blanchelike lesions; reticulate hyperpigmentation JAAD 63:602–606, 2010; JAAD 57:840–848, 2007; BJD 146:694–699, 2002; anti-phosphatidylserine-prothrombin complex JAAD 63:602–606, 2010; microscopic PAN JAAD 48:311–340, 2003; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014 Urticarial vasculitis, including urticarial vasculitis associated with mixed cryoglobulins, hepatitis B or C infection, IgA multiple myeloma, infectious mononucleosis, monoclonal IgM gammopathy (Schnitzler’s syndrome), fluoxetine ingestion, metastatic testicular teratoma, serum sickness, Sjogren’s syndrome, systemic lupus erythematous – arthralgias, arthritis Cutis 79:41–49, 2007; JAAD 49:S283–285, 2003; JAAD 38:899–905, 1998; Medicine 74:24–41, 1995; JAAD 26:441–448, 1992; hypocomplementemic vasculitis (urticarial vasculitis) – arthralgias JAAD 48:311–340, 2003 Vasculitis - leukocytoclastic vasculitis AD 134:309–315, 1998 Venous leg ulcers and arthropathy Br J Rheumatol 29:142–144, 1990 Venous malformations (genuine diffuse phlebectasia) (Bockenheimer syndrome) – musculoskeletal hypotrophy with

Aseptic Meningitis, Cutaneous Manifestations synovial siderosis; degenerative arthritis with amyotrophy of leg, flexions contractures; ankylosis of the knee JAAD 65:893–906, 2011

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Herpes zoster BMJ Case Reports Feb 17, 2015 HIV acute infection NEJM 360:1540–1548, 2009 Kawasaki’s disease

 SEPTIC MENINGITIS, CUTANEOUS A MANIFESTATIONS Acanthamoeba Am J Med 67:891, 1979 Aicardi-Goutieres syndrome – autosomal recessive; chilblains, acrocyanosis, livedo reticularis, puffy hands and feet; distal tapering of fingertips; blueberry muffin baby; congenital progressive encephalopathy, basal ganglia intracranial calcification with enlarged ventricles; increased interferon alpha in blood and cerebrospinal fluid and CSF lymphocytosis Ped Derm 26:432–435, 2009; JAAD 61:727–728, 2009; Ped Derm 26:432–435, 2009; Am J Hum Genet 81:713–725, 2007; Eur J Paediatr Neurol 69 (Suppl A):A1–A7, 2002; Ann Neurol 44:900–907, 1998 Arthropathy, rash, chronic meningitis, eye lesions, mental retardation Jnl Ped 99:79, 1981 Behcet’s syndrome CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of lateral forehead, gynecomastia, wide spaced nipples, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, splenomegaly, protuberant abdomen bjd 170:215–217, 2014; JAAD 68:834–853, 2013; Ped Derm 28:538–541, 2011; JAAD 62:487–495, 2010 Chlamydia pneumonia – atypical erythema nodosum Scand J Inf Dis 25:259–261, 1993 Ciguatera dermatitis – ciguatoxin produced by dinoflagellates (Gambierdiscus toxicus) – Caribbean and Gulf of Mexico JAAD 61:733–750, 2009 Coxsackie A9 – generalized non-pruritic morbilliform eruption and aseptic meningitis BMC Inf Dis Jan 24, 2013

Kikuchi’s disease (histiocytic necrotizing lymphadenitis) Medicine 93:372–382, 2014 Systemic lupus erythematosus Lyme disease (Borrelia burgdorferi) Neuro-Sweet’s syndrome JAAD 71:192–193, 2014 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – urticarial lesions, chronic meningitis, arthralgias of knees and ankles with deforming arthropathy with epiphyseal bone formation, deafness, hepatosplenomegaly, uveitis, vitreitis, papilledema, corneal stromal keratopathy; mental retardation; fever and rash more severe in evening; mutation in NLRP3 (CIAS 1) which encodes cryopyrin AD 144:392–402, 2008; AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319– 321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005 Parvovirus B19 infection Ped Inf Dis J 25:898–901, 2006 Relapsing polychondritis Rickettsia japonica Intern Med 51:783–786, 2012 Rocky Mountain spotted fever Sarcoidosis Scleromyxedema – neurocutaneous syndrome Scrub typhus Strongyloidiasis, hyperinfection JAAD 70:1130–1134, 2014 Sweet’s syndrome Ocul Immunol Inflamm 19:167–170, 2011 Syphilis, secondary TRAPS syndrome; CINCA syndrome Vogt-Koyanagi-Harada syndrome West Nile virus J Neurol Sci 200:63–66, 2002

ATRICHIA AND NAIL ABNORMALITIES

Cryopyrin-associated periodic syndrome (CAPS) – early childhood, periodic fever, skin rash, osteoarthropathy, aseptic meningitis, sensorineural hearing loss, optic neuritis

Ped Derm 5:236–342, 1988

Cytomegalovirus

Alopecia, onychodysplasia, hypohidrosis

DRESS syndrome – meningitis, encephalitis, cerebral vasculitis, SIADH; headache, seizure, coma, speech abnormalities, cranial nerve palsies, muscle weakness Intern Med 52:1403–1405, 2013; Ann Neurol 51:771–774, 2002

Arthrogryposis and ectodermal dysplasia

Agammaglobulinemia, dwarfism, ectodysplasia Alopecia, onychodysplasia, hypohidrosis, deafness

Atrichia with nail dystrophy, abnormal facies and retarded psychomotor development

Drug-induced  Dapsone Korean J Ped 56:260–264, 2013  Ipilimumab PLOS One 8:e53745, 2013

Atrichia with papular lesions - autosomal recessive

Echovirus 18 J Med Micro 60:1360–1365, 2011

Dermotrichic syndrome

Enterovirus – persistent enterovirus encephalitis in X-linked agammaglobulinemia and dermatomyositis NEJM 304:1278, 1981

Ectodysplasia with severe mental retardation

Familial Mediterranean fever

Hayden’s syndrome

Granulomatosis with polyangiitis

Hidrotic ectodermal dysplasia of Clouston - autosomal dominant

Herpes simplex

Infantile progeria - autosomal recessive

Herpes virus 6 – roseola infantum J Formos Med Assoc 90:579– 582, 1991

Odontoonychodysplasia with alopecia

Atrichia - isolated atrichia - autosomal dominant; autosomal recessive

GAPO - autosomal recessive

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Palmoplantar hyperkeratosis and alopecia

METABOLIC DISORDERS

Skeletal anomalies, ectodermal dysplasia, growth and mental retardation

Acrodermatitis enteropathica Cutis 81:314, 324–326, 2008; Ped Derm 19:180–182, 2002; J Oral Pathol Med 23:168–171, 1994; AD 116:562–564, 1980; Dermatologica 156:155–166, 1978; acquired zinc deficiency

Trichoonychodysplasia with keratoderma X-linked hypohidrotic ectodermal dysplasia

Celiac disease – atrophic burning tongue NEJM 356:2547, 2007; Dermatol Clin 21:123–124, 2003

ATROPHIC GLOSSITIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSREGULATION Bullous diseases, chronic Graft vs. host reaction, chronic AD 134:602–612, 1998 Morphea, linear (en coup de sabre) Scleroderma Sjogren’s syndrome Dermatol Clin 21:123–124, 2003

CONGENITAL DISORDERS Congenital erosive and vesicular dermatosis healing with reticulated supple scarring – atrophic tongue, anonychia AD 121:361–367, 1985

Deficiency of:   folic acid J Gen Intern Med 6:137–140, 1991    iron J Nutrition 120:28, 1999; transferrin deficiency   niacin – pellagra Int J Derm 43:1–5, 2004; JCI 31:533–542, 1952   pyridoxine (B6)  riboflavin (B2) – tongue is purple, red, and smooth Clinics in Derm 17:457–461, 1999; J Gen Intern Med 6:137–140, 1991; AD 112:70–72, 1976  thiamine J Gen Intern Med 6:137–140, 1991; JCI 31:533–542, 1952   Vitamin A J Gen Intern Med 6:137–140, 1991   Vitamin B12 - pernicious anemia NEJM 370:773–773–776, 2014; Ann DV 130:191–194, 2003   Vitamin E J Am College Nutrition 12:14–20, 1993   zinc Malabsorption Malnutrition Pernicious anemia

DRUGS Cancer chemotherapy Corticosteroids - inhaled Am Rev Resp Dis 141:S89–96, 1990

Plummer-Vinson syndrome – iron deficiency; esophageal cancer of post-cricoid area; koilonychias, atrophic tongue, pallor due to Arch Int Med 155:2008–2010, 1995 Protein/calorie deficiency Age Aging 29:47–50, 2000; J Gen Intern Med 6:137–140, 1991

EXOGENOUS AGENTS

Pseudoglucagonoma syndrome due to malnutrition AD 141:914– 916, 2005

Betel nut chewing - smooth tongue JAAD 37:81–88, 1998

Vitamin A intoxication

Bidi smokers in India J Oral Pathol Med 18:475–480, 1989

Vitamin B12 deficiency (pernicious anemia) – Hunter’s glossitis (Moeller’s glossitis) – beefy red tongue with atrophy of lingual papillae NEJM 370:773–776, 2014; JAAD 60:498–500, 2009

INFECTIONS AND INFESTATIONS AIDS Candidiasis; post-open heart surgery atrophic glossitis Scand J Thorac Cardiovasc Surg 22:143–144, 1988; candida atrophic glossitis due to steroid inhalant - personal observation Coliform bacteria – Pseudomonas, Klebsiella species, Proteus J Oral Pathol Med 23:168–171, 1994 Median rhomboid glossitis (central papillary atrophy of the tongue); Int J Oral Maxillofac Surg 15:32–325, 1986 Staphylococcus aureus J Oral Pathol Med 23:168–171, 1994 Syphilis, tertiary Diseases of the Tongue 1986, Van der Waal/ Pinburg; OSOMOP 30:192–195, 1970

INFILTRATIVE DISORDERS

NEOPLASTIC DISEASES Submucous fibrosis Squamous cell carcinoma

PRIMARY CUTANEOUS DISEASES Epidermolysis bullosa, recessive dystrophic - symblepharon Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 135–151 Geographic tongue J Am Dent Assoc 115:421–424, 1987 Lichen planus – loss of filiform papillae J Oral Pathol 14:431–458, 1985 Lichen sclerosus et atrophicus

Amyloidosis Dermatol Clin 21:123–124, 2003

Xerostomia in terminally ill patients Oral Oncol 34:123–126, 1998

INFLAMMATORY DISORDERS

SYNDROMES

Stevens-Johnson syndrome, sequela BJD 177:924–935, 2017; AD 145:1332–1333, 2009

Cronkhite-Canada syndrome - smooth tongue Cutis 61:229–232, 1998

Toxic epidermal necrolysis, healed

Dyskeratosis congenita- personal observation

Atrophic Lesions Familial dysautonomia(Riley-Day syndrome) (hereditary sensory and autonomic neuropathy type III) – absent fungiform papillae Genetic Skin Disorders, Second Edition, 2010, pp.479–482; AD 89:190–195, 1964; smooth tongue; absent fungiform papillae Cesk Pediatrics 46;347–348, 1991Glucagonoma syndrome - alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; skin rash, angular stomatitis, cheilosis, beefy red glossitis, blepharitis, conjunctivitis, alopecia, crumbling nails; rarely, associated with MEN I or IIA syndromes JAAD 68:189–209, 2013; AD 143:1221–1222, 2007; AD 133:909, 912, 1997; JAAD 24:473–477, 1991; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979 Kawasaki’s syndrome – red strawberry tongue NEJM 373;467, 2015 Odonto-onycho-dermal dysplasia – telangiectatic atrophic patches of face, sparse hair, conical teeth, oligodontia, hyperkeratosis of palms and soles, smooth tongue, dystrophic nails; WNT10A mutation JAAD 65:1066–1069, 2011; Am J Med Genet 14:335–346, 1983 Romberg syndrome Arch Neurol 39:44–49, 1982 Xeroderma pigmentosum – atrophic lips and tongue JAAD 75:855–870, 2016

TOXINS Alcoholism - chronic alcoholism Diseases of the Tongue 1986, Van der Waal/Pinburg

TRAUMA Denture use Lingual nerve damage Br Dent J 167:332, 1989 Radiation for squamous cell carcinoma - personal observation Traumatic atrophic glossitis (Riga-Fede disease) Cesk Pediatr 46:347–348, 1991

ATROPHIC LESIONS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Autoimmune lipodystrophy – ¼ associated with dermatomyositis NEJM 350:1220–1234, 2004; J Rheumatol 28:610–615, 2001 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques of face and trunk which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, –limitation of range of motion with plaques over interphalangeal joints; panniculitis, lipoatrophy of cheeks and arms, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis with progressive ear and saddle nose deformities, epidydimitis, cold-induced pernio-like lesions of hands and feet, delayed physical development with short stature, hepato-splenomegaly, protuberant abdomen, conjunctivitis Ped Derm 33:602–614, 2016; JAAD 68:834–853, 2013; JAAD 62:489–495, 2010; Ped Derm 26:654, 2009 C1q deficiency – atrophic fingers and toes, hypopigmentation, finger tapering, butterfly rash, discoid lupus lesions, Raynaud’s phenomenon; renal disease – segmental mesangiopathic glomerulonephritis; increased interferon 1 levels Ped Derm 33:602–614, 2016

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Common variable immunodeficiency (Gottron-like papules) – granulomas presenting as acral red papules and plaques with central scaling, scarring, atrophy, ulceration Cutis 52:221–222, 1993; granulomatous dermatitis with annular atrophic scarred and scaly plaques J Clin Immunol 33:84–95, 2013; Dermatovenereol 18:107–113, 2010; J Clin Immunol 117:878–882, 2006; BJD 147:364–367, 2002; Mt Sinai Med J 68:326–330, 2001 Dermatomyositis – panniculitis with lipoatrophy in children JAAD 55:947–950, 2006; lipoatrophy associated with juvenile dermatomyositis – associated with anti-p155 antibodies JAMA 305:183–190, 2011; J Rheumatol 28:610–615, 2001; Ped Derm 13:477–482, 1996; JAAD 28:348–351, 1993; JAAD 22:966–969, 1990; lipoatrophy associated with adult dermatomyositis JAAD 57:S85–87, 2007; nodules and plaques on arms, thighs, buttocks, abdomen with lipoatrophy AD 127:1846–1847, 1991; JAAD 23:127–128, 1990; association with hypocomplementemia (C3 nephritic factor) NEJM 294:461–465, 1976; associated with partial lipodystrophy JAAD 28:348–351, 1993; asymmetric lipoatrophy JAAD 22:966–969, 1990; longstanding dermatomyositis - lipodystrophy-like appearance (hirsutism, loss of subcutaneous fat, acanthosis nigricans) Epidermolysis bullosa acquisita JAAD 24:706–714, 1991; extensive scarring and mutilation in EBA AD 131:590–595, 1995 Graft vs. host disease, chronic - atrophic hyperpigmented plaques BJD 156:1032–1038, 2007; JAAD 38:369–392, 1998; anetoderma AD 138:924–934, 2002 Lupus erythematosus - discoid lupus erythematosus NEJM 269:1155–1161, 1963; DLE with spindly atrophy of fingers with hyperextension of distal phalanges Rook p. 2448, 1998, Sixth Edition; lupus panniculitis (lupus profundus) – atrophic scarring J Cutan Pathol 28:235–247, 2001; Lupus 10:514–516, 2001; J Rheumatol 26:68–72, 1999; AD 103:231–242, 1971; lupus profundus with secondary anetoderma Rook p. 2451, 1998, Sixth Edition; neonatal lupus Ped Derm 15:38–42, 1998; acquired generalized lipodystrophy in systemic lupus erythematosus BJD 175:225–226, 2016; congenital lupus erythematosus - erosions with atrophy and scarring Ped Derm 27:109–111, 2010; generalized elastolysis with SLE JAAD 8:869–873, 1983; nodular cutaneous lupus mucinosis - atrophie blanche-like lesions J Dermatol 21:674–679, 1994; secondary anetoderma with SLE, DLE, or lupus profundus Ann DV 115:679–685, 1988; partial lipodystrophy - association with hypocomplementemia (C3 nephritic factor) NEJM 294:461–465, 1976; tumid lupus (lupus erythematosus telangiectoides) – reticulate telangiectasias of face, neck ears, hands, breasts, heels, sides of feet; punctate atrophy JAAD 41:250–253, 1999; discoid lupus with annular atrophic plaques of face, neck, behind ears AD 112:1143–1145, 1976; neonatal lupus Ped Derm 22:240– 242, 2005 Mixed connective tissue disease Morphea – generalized deep morphea (subcutaneous morphea) leading to deep atrophy Semin Cutan Med Surg 26:90–95, 2007; Clin Dermatol 24:374–392, 2006; Mayo Clin Proc 70:1068–1076, 1995; linear JAAD 59:385–396, 2008; linear (en coup de sabre) – linear atrophy BJD 169:1265–1271, 2013; Ped Derm 29:738–748, 2012; JAAD 56:257–263, 2007; generalized morphea pansclerotic morphea – marked decrease of subcutaneous fat; reduced acral bone density Ped Derm 19:151–154, 2002; superficial morphea personal observation PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears,

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chin; atopy; recurrent sinopulmonary infections JAMA Derm 151:627–634, 2015 Rheumatoid arthritis - generalized thinning of skin (transparent skin) JAAD 53:191–209, 2005; Am J Med 54:445–452, 1973; Ann Rheum Dis 24:219–223, 1965 Scleroderma – atrophy of skin of face, hands; sclerodactyly with tapered fingers; atrophy of terminal phalanges linear scleroderma of the leg BJD 156:1363–1365, 2007; pitted scars of finger tips (acral pits), ulnar border of thumb, radial borders of second and third fingers, dorsal fingers over joints; sclerosis with atrophic phalanges; mandibular atrophy Dermatology 187:104–108, 1993; atrophie blanche around ankles STING-associated vasculopathy with onset in infancy (SAVI) (type 1 interferonopathy) – red plaques of face and hands; violaceous and telangiectatic malar plaques, chilblain-like lesions with red-purpuric plaques over cold-­sensitive areas (acral areas) (cheeks, nasal tip, ears),; reticulate erythema of arms and legs; atrophic plaques of hands, telangiectasias of cheeks, nose, chin, lips, acral violaceous plaques and acral cyanosis (livedo reticularis of feet, cheeks, and knees), distal ulcerative lesions with infarcts (necrosis of cheeks and ears), progressive digital necrosis with gangrene of fingers or toes with ainhum, swelling of fingers, amputation of several digits, chronic leg myalgias, atrophic skin over knees, nasal septal perforation, nail dystrophy; small for gestational age; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis with ground glass and reticulate opacities; gain of function mutation in TMEM173 (stimulator of interferon genes); mimics granulomatosis with polyangiitis JAAD 74:186–189, 2016; JAMA Derm 151:872–877, 2015; NEJM 371:507–518, 2014

CONGENITAL Amniocentesis – punctate scars and dimples Ped Derm 2:140–142, 1984; Am J Obstet Gynecol 126:247–252, 1976 Anetoderma of prematurity Clin in Dermatol 29:633–643, 2011; AD 146:565–567, 2010 Aplasia cutis congenita associated with fetus papyraceus – cutaneous ulcers, linear atrophic scars, atrophic scars of scalp, dystrophic nails Ped Derm 32:858–861, 2015 Atrophic linear bands (acquired raised bands of infancy) – associated with amniotic band syndrome Int J Dermatol 27:312–314, 1988 Ped Derm 22:346–349, 2005 Congenital atrophic patch of branchial cleft - personal observation Congenital anetoderma Ped Derm 25:626–629, 2008; in twins JAAD 36:483–485, 1997 Congenital constriction band of the trunk (variant of amniotic band syndrome) Ped Derm 14:470–472, 1997 Congenital enteric sinus cyst (split notochord syndrome) – pit Ped Derm 20:221–224, 2003 Congenital erosive and vesicular dermatitis with reticulate supple scarring - thin and translucent skin Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995, Ped Derm 15:214–218, 1998; JAAD 17:369–376, 1987; AD 121:361–367, 1985 Congenital midline fusion defect - personal observation Congenital cutis laxa – abdomen; dysplasia of abdominal muscles Congenital ulcer of the buttock with pits of knees Ped Derm 31:726–728, 2014 Dorsal dermal sinus

Facial fusion defect (focal preauricular dermal dysplasia) (form of aplasia cutis congenital) – linear array of white atrophic patches of lateral cheeks Ped Derm 25:344–348, 2008Linear telangiectatic erythema and mild atrophoderma Cutis 39:69–70, 1987 Hair collar sign - with protruding scalp mass – aplasia cutis with sinus pericranii; irregular plaque of aplasia with yellow crusts and prominent blood vessels Ped Derm 37:40–51, 2020 Melanocytic nevus - hypoplasia underlying a giant congenital melanocytic nevus Ped Derm 17:387–390, 200 Midline cervical clefts – vertically oriented atrophic area of lower anterior neck, associated skin tags or sinus tracts, fibrous bands connect to platysma muscle AD 141:1161–1166, 2005; Int J Derm 19:479–486, 1980 Myelomeningocele Myxo-papillary ependymal rest – dimple; skin-colored pedunculated papule near gluteal cleft; heterotopic neuroglial tissue JAAD 65:851–854, 2011 Nasal dermoid sinus cyst – pit of central nose with wisps of terminal hair Ped Derm 24:646–650, 2007 Pre-auricular skin defects AD 133:1551–1554, 1997 Ring chromosome 13 syndrome - scalp defect Sacral dimples Semicircular lipoatrophy of thighs Cutis 80:464, 477–478, 2008 Sequestrated meningocele (rudimentary meningocele) (type I cutaneous meningioma) AD 137:45–50, 2001; indented scarred patch of vertex of scalp JAAD 57:1101–1102, 2007 Smooth muscle hamartoma – follicular indentations; generalized congenital smooth muscle hamartoma – inguinal and sacral redundancy with hypertrichosis Ped Derm 25:236–239, 2008 Spinal dysraphism with overlying dimple, sinus, lipoma, faun tail nevus, dermoid cyst, hemangioma, port wine stain BJD 156:1065– 1066, 2007; Eur J Paediatr Neurol 2:179–185, 1998; Pediatr Clin North Am 47:813–823, 2000; AD 112:1724–1728, 1976 Sternal cleft (congenital midline presternal atrophic defect of the chest) - congenital atrophic dimple or scar of upper chest Supraumbilical cleft Trisomy 13 - scalp defects Varicella – scarring over dermatomes, limb hypoplasia, low birth weight, mild mental retardation, cataract, chorioretinitis Lancet i:1547–1550, 1994 Congenital xanthogranulomas Ped Derm 35:582–587   Yellow scalp nodule   Ulcerated pink nodule   Subcutaneous nodule with pink papules   Brown-gray patch with pink yellow papules   Atrophic patch with yellow macules and papules

DEGENERATIVE Age-related fine wrinkling (crinkling) and laxity Age-related facial lipoatrophy JAAD 59:923–933, 2008 Amyotrophic lateral sclerosis – interosseous muscle atrophy - personal observation Inclusion body myositis – forearm atrophy Neuralgic amyotrophy – asymmetric atrophy of shoulder muscles NEJM 362:2304, 2010 Neuropathic skin atrophy - personal observation

Atrophic Lesions

DRUG-INDUCED Anti-HIV drugs, including nucleoside reverse transcriptase inhibitors, protease inhibitors, and non-nucleoside reverse transcriptase inhibitors – lipoatrophy, lipohypertrophy, gynecomastia; with metabolic syndrome JAAD 63:549–561, 2010 Bleomycin - scaly linear erythema of dorsa of hands with atrophy and telangiectasia (dermatomyositis-like) JAAD 48:439–441, 2003; intralesional bleomycin A5 for infantile hemangiomas – subcutaneous atrophy Ped Derm 32:188–191, 2015 Corticosteroid atrophy – systemic, intralesional, topical corticosteroids J Drugs Dermatol 6:550–551, 2013; JAAD 54:1–15, 2006; AD 126:1013–1014, 1990; perilesional linear atrophic streaks JAAD 55:947–950, 2006; JAAD 45:325–361, 2001; Ped Derm 4:259–260, 1987; linear atrophy due to intralesional corticosteroid injections of de Quervain tendonitis Cutis 73:197–198, 2004; oral, inhaled, topical-induced acne rosacea – papules, pustules, atrophy, telangiectasia Clin Exp Dermatol 18:148–150, 1993; AD Forsch 247:29–52, 1973; multifocal lipoatrophy due to intravenous cortisol JAAD 46:S130–132, 2002; striae; intra-articular corticosteroid injection Drug-induced lipodystrophy (post-injection lipodystrophy) – insulin, corticosteroids, antibiotics JAAD 55:947–950, 2006; JAAD 45:325–361, 2001; Am J Med 108:143–152, 2000 Hydroxyurea – atrophic, scaling, poikilodermatous patches with erosions on the backs of the hands, sides of the feet JAAD 45:321–322, 2001; atrophy of skin and subcutaneous tissue JAAD 36:178–182, 1997 Indinavir (protease inhibitor) - striae JAAD 41:467–469, 1999; lipodystrophy and abnormal fat distribution (crix belly – central adiposity) JAAD 46:284–293, 2002 Insulin injection lipoatrophy – dimple or more extensive area of atrophy Ped Derm 11:310–314, 1994 Pegylated alpha-interferon injection sites – Degos’ disease (atrophic papulosis) BJD 170:992–994, 2014 Methimazole and carbimazole - aplasia cutis congenita Ped Derm 3:327–330, 1986 Methotrexate – semicircular lipoatrophy Ped Derm 19:432–435, 2002 Misoprostol – extensive frontotemporal defects of scalp and temporal bones Clin Dysmorphol 2:76–80, 1993 Nelfinavir (protease inhibitor) – lipodystrophy and abnormal fat distribution (crix belly – central adiposity); striae JAAD 46:284–293, 2002 Penicillamine dermatopathy AD 125:92–97, 1989; atrophic elastosis of mucosal lip JAAD 60:700–703, 2009 Phytonadione (fat soluble Vitamin K) injection - sclerodermiform atrophic plaques AD 137:957–962, 2001; AD 121:1421–1423, 1985; Cutis 43:364–368, 1989; JAAD 38:322–324, 1998; Cutis 61:81–83, 1998 Protease inhibitors, including indinavir, ritonavir, saquinavir, nelfinavir, lopinavir, amprenavir and fosamprenavir, atazanavir, tipranavir – facial lipoatrophy BJD 142:496–500, 2000; lipodystrophy of face, arms, legs, and buttocks with central fat accumulation of abdomen, breasts, and dorsocervical fat pad JAAD 63:549–561, 2010; JAAD 50:809–810, 2004 Saltpeter-induced PXE like changes Saquinavir (protease inhibitor) – lipodystrophy and abnormal fat distribution (crix belly – central adiposity); striae JAAD 46:284–293, 2002

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Stavudine (nucleoside reverse transcriptase inhibitor) +/- didanosine – lipoatrophy, lipohypertrophy, gynecomastia JAAD 63:549– 561, 2010 Subcutaneous injection of anti-sense oligonucleotides – lipodystrophy JAMA Derm 155:1084–1086, 2019 Voriconazole – advanced photoaging AD 146:300–304, 2010; JAAD 52:S81–85, 2005

EXOGENOUS AGENTS Coal tar products – pitch, asphalt, creosote – diffuse melanosis of exposed skin; evolves to atrophy, telangiectasia, lichenoid papules, follicular keratosis Smoker’s face – linear wrinkling and atrophy AD 128:255–262, 1992 Sulfur spring dermatitis – painful punched out erosions and pits Cutis 94:223–225, 2014

INFECTIONS AND INFESTATIONS AIDS - lipoatrophy of face, arms, and legs (associated with increase fat of neck and abdomen); SREBP and PPARgamma dysfunction NEJM 350:1220–1234, 2004; JAAD 59:923–933, 2008; JAAD 42:727–730, 2000; Am J Med 108:143–152, 2000 Cutaneous Borreliosis – acrodermatitis chronica atrophicans, cutis laxa-like changes, red patches, erythema migrans, erythema and edema of foot, poikilodermatous changes, red macules and telangiectasias JAAD 72:683–689, 2015 Botryomycosis – granulomatous reaction to bacteria with granule formation; single or multiple abscesses of skin and subcutaneous tissue break down to yield multiple sinus tracts; small papule; heals with atrophic scars; extremities, perianal sinus tracts, face Int J Dermatol 22:455–459, 1983; AD 115:609–610, 1979 Chronic tropical folliculitis Herpes simplex; congenital herpes simplex infection due to intrauterine infection - generalized cigarette paper atrophy J Pediatr 110:97–101, 1987; Ped Derm 4:336–340, 1987 HIV disease - anetoderma AD 128:661–662, 1992; lipodystrophy of AIDS Am J Med 108:143–152, 2000 Leishmaniasis – atrophic depressed scars JAAD 73:897–908, 2015; leishmania recidivans – central atrophy with verrucous border Clin Dermatol 38:140–151, 2020 Leprosy - secondary anetoderma; Lucio’s phenomenon – atrophic scars JAAD 48:958–961, 2003 Lyme borreliosis (Borrelia burgdorferi) - acrodermatitis chronica atrophicans – red to blue nodules or plaques; tissue-paper-like wrinkling; pigmented; poikilodermatous; dorsal hands, feet, elbows, knees; subcutaneous nodules of elbows and knees, with ulnar fibrous bands; sclerosis of lower legs with ulceration; violaceous patches JAAD 74:685–692, 2016; Clin Inf Dis 59:866,903, 2014; BJD 171:528–543, 2014; JAAD 64:619–636, 2011; JAAD 49:363– 392, 2003; BJD 121:263–269, 1989; Int J Derm 18:595–601, 1979; annular erythematous slightly atrophic patches of ankles and feet Clin Inf Dis 57:1751,1782–1783, 2013 Molluscum contagiosum, healed – cribriform scarring BJD 144:1094–1095, 2001 Mycobacterium tuberculosis – red plaque with papules and central atrophy SKINmed 10:28–33, 2012; secondary anetoderma; varioliform scars of papulonecrotic tuberculid JAAD 76:730–735, 2017

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Onchocerciasis – atrophic changes earliest of buttock, shoulders, and legs; fine wrinkling and xerotic skin; dermatitis and depigmentation JAAD 73:929–944, 2015; BJD 171:1078–1083, 2014; AD 140:1161–1166, 2004; JAAD 45:435–437, 2001; BJD 121:187–198, 1989; atrophic white macules, "hanging groin" due to destruction of elastic fibers Cutis 65:293–297, 2000

atrophy Ped Derm 28:146–148, 2011; Ped Derm 28:142–145, 2011; J Cut Pathol 38:270–274, 2011; AD 146:877–881, 2010

Pinta – late secondary phase hypopigmented, depigmented hyperpigmented atrophic skin; tertiary (late phase) – atrophy with thinning and wrinkling of skin overlying large joints

Febrile idiopathic lobar panniculitis of childhood – abdominal pain, arthralgia, fever, red nodules of face, legs, trunk, lipoatrophy Ped Derm 31:652, 2014

Pustular dermatitis atrophicans of the legs - folliculitis in Lagos, West Africa

Lipoatrophic panniculitis(lipophagic panniculitis of childhood; annular atrophy of the ankles) (mimics atrophoderma of Pasini and Pierini) - red nodules and red plaques of extremities; annular atrophy of ankle and/or dorsal foot AD 146:877–881, 2010; Ped Derm 29:363–364, 2012; AD 123:1662–1666, 1987; primary lipophagic panniculitis of adults Ped Derm 27:53–57, 2010; BJD 124:291–295, 1991; lipoatrophy in lipophagic panniculitis of childhood JAAD 21:971–978, 1989

Rubella, congenital – deep dimples over bony prominences (patellae); blueberry muffin baby J Pediatr 39:291–292, 1967 Syphilis - secondary anetoderma; tertiary syphilis – atrophic scars Tinea versicolor, atrophic variant JAAD 76:730–735, 2017 Varicella – congenital (fetal) varicella syndrome – infection between first and second trimester; dermatomal scars; low birth weight, localized absence of skin, papular lesions resembling connective tissue nevi, limb paresis, limb hypoplasia (atrophic scarred limb), malformed digits, ocular anomalies (chorioretinitis), central nervous system abnormalities BJD 150:357–363, 2004; varicella scars – small circular atrophic scars Yaws – primary red papule, ulcerates, crusted; satellite papules; become round ulcers, papillomatous or vegetative friable nodules which bleed easily (raspberry-like) (framboesia); heals with large atrophic scar with white center with dark halo; tertiary – gumma; multiple subcutaneous nodules; overlying skin ulcerates with purulent discharge; atrophic pigmented scars (tissue paper scars)

Connective tissue panniculitis – nodules, atrophic linear plaques of face, upper trunk, or extremities AD 116:291–294, 1980; connective tissue panniculitis of the ankles (annular atrophy) JAAD 21:1152– 1156, 1989

Panniculitis, various types in children – lipoatrophy Ped Derm 37:572–573, 2020; JAAD 55:947–950, 2006; localized lipoatrophy Am J Med 108:143–152, 2000 Panniculitis and localized lipodystrophy Am J Med 108:143–152, 2000 Nodular panniculitis, idiopathic – heals with atrophic pigmented patch Medicine 64:181–191, 1985 Post-inflammatory elastolysis and cutis laxa (PECL) in children – severe variant of anetoderma in black girls; begins as indurated annular plaque with collarette of scale; progress to finely wrinkled skin JAAD 51:165–185, 2004; JAAD 22:40–48, 1990; S Afr Med J 40:1016–1022, 1966

INFILTRATIVE DISEASES

Pyoderma gangrenosum with cigarette paper atrophy JAAD 18:559–568, 1988; cribriform atrophic scarring

Amyloid - atrophic outpouchings of abdominal skin (nodular cutanous amyloidosis) AD 132:223–224, 226–227, 1996; wrinkling of the fingers with hemodialysis-induced cutaneous amyloid Am J Dermatopathol 16:179–184, 1994; primary cutaneous nodular amyloid – anetoderma Cutis 91:271, 283–284, 2014; J Eur Acad Dermatol Venereol 18:224–226, 2006; AD 122:1425–1439, 1986; familial amyloid polyneuropathy – atrophic scars BJD 152:250–257, 2005;

Sarcoid - atrophic sarcoid – red pretibial plaques with atrophic scars, telangiectasias, venous prominence JAMA Derm 154:955– 956, 2018; annular plaques with cigarette paper wrinkling; elastophagocytosis; annular atrophic plaques Cutis 103:124,130–131, 2019; BJD 172:1156–1158, 2015; Skinmed 8:59–60, 2010; AD 122:320–322, 1986; Acta DV 57:367–379, 1977; BJD 83:255–262, 1970

Benign cephalic histiocytosis - after clearing Ped Derm 11:164–167, 1994

Subcutaneous fat necrosis of the newborn Cutis 54:383–385, 1994

Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease) – generalized scaling atrophic and erosive patches BJD 149:191–192, 2003; anetoderma-like lesions with milia J Pediatr Hematol Oncol 25:270–273, 2003 Erdheim-Chester disease, pediatric - facial plaques, psoriasiform plaques, papulosquamous lesions, annular lesions, central atrophic scarring; osteolysis and osteosclerosis BJD 178:261–264, 2018 Juvenile xanthogranuloma – congenital giant xanthogranuloma after resolution Ped Derm 21:121–123, 2004 Langerhans cell histiocytosis - urticating Langerhans cell histiocytosis (Hashimoto-Pritzker disease) – atrophic chicken pox-like scars Ped Derm 18:41–44, 2001 Lymphoid hyperplasia, benign cutaneous – secondary anetoderma AD 131:365–366, 1995

METABOLIC DISEASES Alpha-1 antitrypsin deficiency panniculitis BJD 174:753–762, 2016 Cachexia in cancer NEJM 351:2124–2125, 2004 Complement deficiency (C3) disorders – partial lipodystrophy Clin Exp Dermatol 21:131–134, 1996 Congenital disorders of glycosylation (CDG-If) – pitting of fat Ped Derm 22:457–460, 2005 Cushing’s disease – striae Ped Derm 15:253–258, 1998; slender wasted extremities Semin Dermatol 3:287–294, 1984 Cystinosis – skin atrophy and telangiectasia mimicking premature aging; normal skin; subcutaneous plaques JAAD 62:AB26, 2010; JAAD 68:e111–116, 2013

INFLAMMATORY DISEASES

Diabetes mellitus – diabetic dermopathy (annular atrophic patches of legs) JAAD 58:447–451, 2008; Am J Med Sci 251:570–575, 1966; AD 93:282–286, 1966; AD 92:625–634, 1965; Acta Med Scand 176 (Suppl)1–75, 1964; pigmented hypertrichotic indurated plaques of thighs Ped Derm 24:101–107, 2007; atrophic brown scars Cutis 3:955–958, 1967

Annular atrophic connective tissue panniculitis – erythematous nodules and plaques of ankles followed by circumferential band of

Hepatocutaneous syndrome – in chronic active hepatitis; firm red papules leaving atrophic scars Br Med J i:817, 1977

Urticaria pigmentosa (mastocytosis) with secondary anetoderma AD 128:105–110, 1992

Atrophic Lesions Homocystinuria – cystathionine-beta synthase deficiency; thin transparent skin; striae; tissue paper scarring of hands JAAD 64:1175–1178, 2011; Int J Cardiol 134:251–254, 2009; Indian J Dermatol Venereol Leprol 74:375–378, 2008; JAAD 46:161–183, 2002; JAAD 40:279–281, 1999 Hypophosphatasia – generalized wasting NEJM 370:959–966, 2014; shallow depressions to deep pits of skin Hypopituitarism – fine wrinkling with aged appearance Dermatol in Gen Med 7th Edition, pp.1483–1484, 2008 Hypothyroidism – pale, cold, scaly, wrinkled skin JAAD 26:885–902, 1992 Leukocyte adhesion deficiency type 1 – autosomal recessive; pyoderma gangrenosum leg ulcers healing with flaccid scarring; absence of defect of beta2 integrin subunit (CD 18); delayed separation of umbilical stump; recurrent skin and systemic infections; abnormal wound healing Ped Derm 27:500–503, 2010; Nat Rev Immunol 7:678–689, 2007; BJD 139:1064–1067, 1998 Malabsorption – generalized atrophic skin Marasmus – severe protein and caloric deprivation; wrinkled, loose, dry skin; extensive loss of subcutaneous fat JAAD 21:1–30, 1989 Menopause - atrophic vulvovaginitis Necrobiosis lipoidica diabeticorum Int J Derm 33:605–617, 1994; JAAD 18:530–537, 1988 Neonatal thyrotoxicosis – generalized loss of subcutaneous fat; exophthalmos NEJM 370:1237, 2014 Nephrogenic fibrosing dermopathy – generalized elastolysis following resolution of nephrogenic fibrosing dermopathy AD 145:183–187, 2009; JAAD 53:174–176, 2005 Nephrogenic systemic fibrosis – shiny skin, sclerodermoid changes, joint contractures JAAD 61:868–874, 2009; late stage anetoderma (cutaneous wrinkling); due to gadolinium AD 145:183–187, 2009 Obesity – striae distensae JAAD 81:1037–1057, 2019 Osteogenesis imperfecta

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NEOPLASTIC DISEASES Basal cell carcinoma, morphea-like Basal cell nevus (linear basal cell nevus) – resemble comedones; usually linear translucent telangiectatic papules, may ulcerate; macular hypopigmentation, alopecia, cysts, striae Cutis 46:493– 494, 1990; BJD 74:20–23, 1962 Becker’s nevus – with underlying lipoatrophy BJD 129:213, 1993; underlying ipsilateral hypoplasia of the breast, hypoplasia of underlying musculature, lipoatrophy, underlying skeletal anomalies (scoliosis, hemivertebrae, fused or accessory cervical ribs, pectus excavatum or carinatum, internal tibial torsion) Semin Cut Med Surg 26:221–230, 2007; Becker’s nevus over entire leg with lipoatrophy JAMA Derm 149:1115, 2013 Dermal dendrocyte hamartoma – medallion-like; annular brown or red-brown congenital lesion of central chest with slightly atrophic wrinkled surface JAAD 51:359–363, 2004; AD 126:794–796, 1990; oval atrophic plaque BJD 160:190–193, 2009 Dermatofibroma - atrophic dermatofibroma Dermatol Surg 28:1085–1087, 2002; J Dermatol 22:334–339, 1995; JAAD 25:1081–1082, 1991; depressed pigmented lesion BJD 158:840– 842, 2008; dermatofibroma with secondary anetoderma Dermatofibrosarcoma protuberans - in adenosine deaminase deficiency (form of SCID) (atrophic variant of dermatofibrosarcoma protuberans); atrophic plaque mimicking dermal dendritic hamartoma; 3–6mm atrophic hyperpigmented papules and plaques JAMA Derm 155:1075–1076, 2019; Ped Derm 33:359–360, 2016;Ped Derm 31:676–682, 2014; Cutis 74:237–242, 2004; Cutis 74:237– 242, 2004; JAAD 49:761–764, 2003; BJD 139:719–725, 1998; congenital Ped Derm 25:455–459, 2008; atrophic blue patch Ped Derm 25:317–325, 2008; AD 139:207–211, 2003 Congenital multiple clustered dermatofibroma – hyperpigmented patch with papules and some depressed areas Ped Derm 31:105– 106, 2014; J Cutan Pathol 37:e42–45, 2010; BJD 142:1040–1043, 2000

Phenylketonuria – morphea resulting in atrophoderma of Pasini and Pierini with subcutaneous atrophy JAAD 49:S190–192, 2003

Desmoplastic trichoepithelioma – atrophic scar-like lesions

Porphyria - porphyria cutanea tarda Am J Med 67:277–286, 1979; congenital erythropoietic porphyria – atrophic scarring; sclerodactyly with crusted papules on dorsal hands; atrophic scars, erythrodontia BJD 166:697–699, 2012; Ped Derm 20:498–501, 2003; Semin Liver Dis 2:154–63, 1982; X-linked dominant variant; mutation in delta-aminolevulinate synthase 2 (ALAS2 gene) BJD 162:642–646, 2010; erythropoietic protoporphyria – weathered wrinkled appearance JAMA Derm 152:1258–1261, 2016; BJD 171:412–414, 2014

Fibroblastic connective tissue nevus Ped Derm 36:397–399, 2019

Pregnancy – striae Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987 Starvation, cachexia, refeeding NEJM 328:490–495, 1993; J Clin Endocrinol Metab 41:60–69, 1975 Thyrotoxicosis, neonatal – retraction of eyelids (thyroid stare), loss of subcutaneous fat NEJM 370:1237, 2014

Extramammary Paget’s disease Fibrous hamartoma of infancy – dimpled subcutaneous mass with hypertrichosis; bony remodeling and muscle atrophy Ped Derm 36:677–680, 2019 Granulomatous slack skin syndrome – due to CD30+ T-cell lymphoproliferative disorder JAAD 50:54–58, 2004; BJD 147:998– 1002, 2002 Infantile myofibromatosis - dimple Ped Derm 8:306–309, 1991; atrophic scarring after resolution Ped Derm 19:520–522, 2002; Curr Prob Derm 14:41–70, 2002; JAAD 41:508, 1999; atrophic dells in the newborn Cutis 78:33–35, 2006 Lymphoma - cutaneous T-cell lymphoma (CTCL) granulomatous slack skin syndrome AD 141:1178–1179, 2005; JAAD 51:165–185, 2004; AD 107:271–274, 1973; BJD 82:397–401, 1970; secondary anetoderma; anetodermic CTCL BJD 158:157–162, 2008; acquired localized cutis laxa due to lymphoplasmacytoid lymphoma AD 131:110–111, 1995; lymphomatoid granulomatosis (angiocentric lymphoma) - red, brown, or violaceous plaques with epidermal atrophy and purpura JAAD 20:571–578, 1989; AD 124:571–576, 1988; B-cell lymphoma overlying acrodermatitis chronica atrophicans associated with Borrelia burgdorferi infection JAAD 24:584– 590, 1991; syringotropic cutaneous T-cell lymphoma – atrophic white papules AD 145:77–82, 2009; anetodermic primary cutaneous B-cell lymphoma – associated with anti-phospholipid antibodies AD 146:175–182, 2010; Arthritis Rheum 36:133–134, 2010; Clin Exp Dermatol 31:130–131, 2006; Actas Dermosifiligr 94:243–246,

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2003; Am J Dermatopathol 23:124–132, 2001; BJD 143:165–170, 2000; lymphoplasmacytoid lymphoma (immunocytoma) – secondary anetoderma AD 131:110–111, 1995; granulomatous slack skin JAAD 50:S4–8, 2004 Medallion-like dermal dendrocyte hamartoma – yellow-brown, blue-brown annular or oval depression of back of neonate; wrinkled surface, telangiectasias; thin hair on surface JAAD 59:169–171, 2008; AD 142:921–926, 2006; wrinkled pliable pink-yellow atrophic patch with plucked chicken appearance of lateral neck Ped Derm 36:397–399, 2019; Ped Derm 27:638–642, 2010

PHOTODERMATITIS Actinic cheilitis J Derm Surg Oncol 7:289–295, 1981 Actinic granuloma (annular elastolytic giant cell granuloma, Miescher’s granuloma) – central wrinkling and atrophy JAMA Derm 152:1045–1046, 2016; AD 142:775–780, 2006; AD 111:460–466, 1975; JAAD 1:413–421, 1979; Eur J Dermatol 9:647–649, 1999; Cutis 62:181–187, 1998; annular lesion with central wrinkling, atrophy, and white depigmentation JAMA Derm 152:1045–1046, 2016

Melanocytic nevus – atrophy (decreased fat and muscle) underlying giant congenital melanocytic nevus BJD 173:1471–1478, 2015; Ped Derm 17:387–390, 2000; Ped Derm 12:272–274, 1995; giant congenital melanocytic nevus with atrophy of an extremity Ped Derm 15:287–289, 1998; anetoderma associated with congenital melanocytic nevi JAAD 39: 843–845, 1998; atrophic nevi

Dermatoheliosis (actinic damage) (photoaging)

Myeloma - acral acquired cutis laxa with myeloma AD 112:835–835, 1976

Abdominal lipoatrophy JAAD 45:325–361, 2001

Myofibroma, infantile – congenital area of atrophy Textbook of Neonatal Dermatology, p.398, 2001; myofibromatosis – atrophic plaque Ped Derm 27:481–484, 2010 Neurofibroma - pseudoatrophic macular variant Cutis 57:100–102, 1996 Nevus anelasticus Int J Dermatol 25:171–173, 1986 Nevus lipomatosis superficialis Nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris) – one case of facial hemiatrophy BJD 67:317–319, 1955 Nevus of striated muscle – atrophic plaque with rippled surface on palmar surface Ped Derm 31:254–256, 2014 Pilomatrixoma – pink nodule of back – anetodermic pilomatrixoma; secondary anetoderma Ped Derm 35:513–514, 2018; JAAD 39:191–195, 1998; JAAD 25:1072–1076, 1991 Porokeratotic adnexal ostial nevus (conifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic lesions with comedones; presents as red patch with red and atrophic linear and curvilinear erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAAD 61:1060–1069, 2009; BJD 103:435–441, 1980; BJD 101:717–722, 1979 Precalcaneal congenital fibrolipomatous hamartoma – annular hyperpigmented patch with cigarette paper wrinkling; resembles nevus lipomatosis superficialis and fibrous hamartoma of infancy AD 148:1073–1078, 2012 Primary cutaneous meningioma – scalp or paraspinal region of children and teenagers with central depression epidermal atrophy Cancer 34:728–744, 1974 Rhabdomyomatous mesenchymal hamartoma – resembling en coup de saber; linear atrophic plaque of chin Ped Derm 36:716– 717, 2019; BJD 162:222–224, 2010; atrophic pink plaque Ped Derm 32:256–262, 2015 Seborrheic keratosis Sequestrated meningioma of scalp with overlying atrophy Ped Derm 14:315–318, 1994 Smooth muscle hamartoma - linear atrophic plaque Ped Derm 13:222–225, 1996

PARANEOPLASTIC Necrobiotic xanthogranuloma with paraproteinemia – atrophy and ulceration of xanthomatous plaques of trunk and extremities Hautarzt 46:330–334, 1995 JAAD 3:257–270, 1980

Stellate pseudoscars BJD 159:479–480, 2008; AD 105:551–554, 1972

PRIMARY CUTANEOUS DISEASES Acne vulgaris – scarring follicular atrophoderma Ped Derm 21:14–17, 2004; secondary anetoderma S/P acne vulgaris Acquired acral lipodystrophy Ped Derm 26:566–568, 2009 Acquired generalized lipodystrophy – acromegalic features JAAD 32:130–133, 1995 Acquired partial lipodystrophy (Weir-Mitchell phenotype) – facial lipoatrophy SKINmed 12:271–275, 2014 Acral localized acquired cutis laxa (palms and soles) JAAD 21:33–40, 1989 Acrodermatitis chronica atrophicans – bluish-red edema of extremities Clin Inf Dis 59:866,903, 2014; Cutis 85:247–252, 2010; BJD 147:375–378, 2002; Arch Dermatol Syph 51:32–45, 1945; Arch Dermatol (Berl) 61:57–76, 1902; Very Ges Dtsch Nature 66, Verslg Wien 1894 II, p.336 Leipzig, 1895; J Cutan Dis 13:1–10, 1895 Acromial dimples Ped Derm 22:412–414, 2005; Ped Derm 11:83, 1994; Ped Derm 9:321–323, 1992; autosomal dominant Hum Genet 76:206, 1987; Arch Dis Child 42:140–146, 1967   Supraspinous (acromial) dimples   Chromosome 18q long arm deletion syndrome – hypotonic children with facial dysmorphy, and mental retardation    Generalized atrophic benign epidermolysis bullosa (GABEB)    Russell Silver syndrome    Trisomy 9p Acute parapsoriasis (Mucha-Habermann disease) – varioliform scarring JAAD 55:557–572, 2006; AD 123:1335–1339, 1987; AD 118:478, 1982; Dermtol Z 45:42–48, 1925; Arch Dermatol Syph (Wien) 123:586–592, 1916; Veth Dtsch Dermatol Ges 4:495–499, 1894 Adermatoglyphia – mutation in SMARCAD1 BJD 171:1521–1524, 2014 Anetoderma of Jadassohn-Pellizari (primary anetoderma) Cutis 81:501–506, 2008; AD 120:1032–1039, 1984; anetoderma of Schweninger-Buzzi Anetodermas, secondary Dermatology 13:123–125, 1998   Acne vulgaris   Alopecia areata AD 128:799–803, 1992   Addison’s disease AD 128:799–803, 1992   Amyloid, nodular AD 122:1425–1430, 1986   Angular cheilitis – linear anetoderma BJD 138:923–924, 1998  Antiphospholipid antibody syndrome or anti-phospholipid antibodies JAAD 60:1–20, 2009; JAAD 56:881–882, 2007; AD 143:109–114, 2007; JAAD 36:149–168, 970–982, 1997   Benign cutaneous lymphoid hyperplasia   B-cell lymphoma  Cutaneous B-cell lymphoproliferative disease Am J Dermatopathol 23:124–132, 2001

Atrophic Lesions  Dermatofibroma Bolognia, p.1542, 2003   Down’s syndrome Ann DV 79:245, 1999   Exocytoses with anetoderma and brachydactyly   Familial anetoderma JAAD 16:341–345, 1987  Folliculitis   Graft vs. host disease AD 138:924–934, 2002   Granuloma annulare JAAD 42:335–338, 2000   Hamartomatous congenital melanocytic nevus   Hepatitis B immunization   Human immunodeficiency virus  Hypothyroidism with antithyroid antibodies AD 128:799–803, 1992   Immunocytoma, multiple cutaneous BJD 143:165–170, 2000  Juvenile xanthogranuloma Ann DV 128:291, 2001; BJD 140:541– 542, 1999  Langerhans cell histiocytosis, vesicular (Hashimoto-Pritzker disease) Clin Exp Dermatol 19:350–352, 1994  Leeches Int J Derm 35 (3):226–227, 1996   Leprosy - lepromatous Dermatologica 135:329, 1967   Lichen planus - personal observation; Bolognia, p.1542, 2003   Lupus erythematosus – systemic or DLE AD 128:799–803, 1992   Lyme disease JAAD 48:S86–88, 2003   Lymphocytoma cutis   Lymphoma – B cell lymphoma, CTCL  Mastocytosis   Melanocytic nevi   Molluscum contagiosum Ped Derm 25:626–629, 2008   Nephrogenic systemic fibrosis - personal observation   Overlying inflammatory processes  Penicillamine  Perifolliculitis  Pilomatrixoma JAAD 25:1072–1076, 1991  Plasmacytoma or benign cutaneous lymphoid hyperplasia AD 131:365–6, 19995  Porphyria (congenital poikiloderma and anetoderma) Arch Argent Dermatol 16:190–194, 1966  Post-inflammatory elastolysis and cutis laxa (PECL) BJD 92:183–190, 1975  Anetoderma of prematurity Eichenfeld, 2001, p.105; AD 133:789, 1997; AD 132:671–674, 1996; anetoderma of prematurity in association with ECG electrodes JAAD 40:479–481, 1999   Prurigo nodularis  Sarcoid   Sjogren’s syndrome Ped Derm 25:626–629, 2008   Staphylococcus epidermidis – perifollicular macular atrophy  Succinate dehydrogenase gene mutation JAMA Derm 155:1317– 1318, 2019   Sweet’s syndrome Ped Derm 25:626–629, 2008   Syphilis – congenital, secondary, tertiary, latent   Takayasu’s arteritis AD 123:796–800, 1987   Tinea versicolor  Tuberculosis   Upper respiratory infection AD 79:516–518, 1959   Urticaria pigmentosa (mastocytosis) Ann DV 108:269–275, 1981  Varicella  Vitiligo AD 128:799–803, 1992  Xanthomas Annular and semicircular lipoatrophies JAAD 20:433–436, 1989 Annular atrophic plaques of the face AD 100:703–716, 1969 Annular lipoatrophy of the ankles – circumferential annular plaques Ped Derm 28:142–145, 2011; Ped Derm 28:146–148, 2011; AD 146:877–881, 2010; JAAD 54:S40–42, 2006; Clin Exp Dermatol 13:111–113, 1988; Acta DV 55:135–140, 1975; AD 102:326–329, 1970

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Aplasia cutis congenita Ped Derm 19:326–329, 2002; giant variant Ped Derm 21:150–153, 2004   I - ACC without multiple anomalies  II - Scalp ACC with associated limb anomalies; hypoplastic or absent distal phalanges, syndactyly, club foot, others (most cases are Adams-Oliver syndrome)   III - Scalp ACC with associated epidermal and organoid nevi  IV - ACC overlying embryologic malformations, such as gastroschisis, omphalocele, meningomyelocele, and others  V - ACC with associated fetus papyraceus or placental infarcts; symmetric linear erosions of extremities Ped Derm 28:467–469, 2011   VI - ACC with epidermolysis bullosa  Junctional EB with pyloric atresia; ACC with gastrointestinal atresia   VII - ACC localized to extremities without blistering   VIII - ACC caused by specific teratogens  IX - ACC associated with malformation syndromes, such as Goltz syndrome, trisomy 13, ectodermal dysplasia, others   Cranial stenosis (Spear-Mickle syndrome) Plast Reconstr Surg 71:413–417, 1983   4p deletion syndrome (chromosome 4 short arm deletion syndrome)   Cutis marmorata telangiectatica congenita JAAD 56:541–564, 2007   Delleman-Orthuys syndrome    Focal facial dermal dysplasia   Johanson-Blizzard syndrome   Goltz syndrome    Amniotic band syndrome    XY gonadal dysgenesis   Adams-Oliver syndrome – cutis marmorata telangiectatica congenita with aplasia cutis congenita of scalp and bony abnormalities of limbs and cranium; congenital cardiac abnormalities JAAD 56:541–564, 2007   SCALP syndrome – sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis JAAD 58:884–888, 2008 Atrophia maculosa varioliformis cutis – linear, varioliform scars JAMA Derm 155:245–246, 2019; BJD 153:821–824, 2005; Ped Derm 18:230–233, 2001; JAAD 30:837–840, 1994; JAAD 21:309, 1989; BJD 115:105–109, 1986; AD 64:59–61, 1951; J Cutan Dis 36:285–288, 1918 Atrophoderma elastolytica discreta Am J Dermatopathol 18:212– 217, 1996 Atrophoderma of Moulin (linear atrophoderma of Moulin) – zosteriform atrophic hyperpigmentation; acquired atrophic pigmented band-like lesions following Blaschko’s lines; reticulated, atrophic, Blaschko lesions JAMA Derm 156:581, 2020; Ped Derm 31:373– 377, 2014; JAAD 65:232–233, 2011; JAAD 49:492–498, 2003; Eur J Dermatol 10:611–613, 2000; Int J Dermatol 39:846–852, 2000; JAAD 38:366–368, 1998; BJD 135:277–279, 1996; Ann DV 119:729–736, 1992 Atrophoderma of Pasini and Pierini JAAD 77:930–937, 2017; Dermatol 190:203–206, 1995; JAAD 30:441–446, 1994; Int J Derm 10:643–645, 1984 Atrophoderma vermiculatum (folliculitis ulerythematosa reticulata) scarring with cribriform depressions; worm-­eaten, reticular, or honeycomb atrophy Cutis 83:83–86, 2009;JAAD 43:310–312, 2000; JAAD 18:538–542, 1988; AD 124:1101–1106, 1988 Balanitis xerotica obliterans

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Blepharochalasis Br J Ophthalmol 72:863–867, 1988; AD 115:479– 481, 1979 Brauer lines – associated with aplasia cutis congenita Centrifugal lipodystrophy – of abdomen in Japanese children AD 126:206–209, 1990; of face BJD 127:407–410, 1992; of neck Dermatology 188:142–144, 1994 Circumscribed palmar or plantar hypokeratosis – red depressed or atrophic pink patch with ridged border of thenar palm BJD 164:211– 213, 2011; JAAD 61:1090–1091, 2009; AD 145:195–200, 2009; JAAD 57:285–291, 2007; JAAD 51:319–321, 2004; JAAD 49:1197– 1198, 2003; JAAD 47:21–27, 2002 Congenital total lipodystrophy (Seip-Berardinelli) JAAD 32:130–133, 1995 Congenital vertex alopecia Cutis laxa – congenital; acquired – with amyloidosis, myeloma AD 112:853–855, 1976; lupus erythematosus, hypersensitivity reaction to penicillin Hautarzt 26:191–198, 1975; complement deficiency, penicillamine, inflammatory skin disease; sarcoidosis, syphilis, Klippel-Trenaunay syndrome JID 75:399–403, 1980; after urticaria and angioedema AD 103:661–669, 1971; generalized cutis laxa – autosomal dominant or autosomal recessive post-inflammatory elastosis and cutis laxa in African children BJD 92:183–190, 1975 Dimples - acromial, facial dimples of the cheeks (familial), sacral Curr Prob Dermatol 13:249–300, 2001 Dimples associated with aberrant positioning during fetal life  Arthrogryposis   Metaphyseal chondrodysplasia   Camptomelic dysplasia   Kyphomelic dysplasia   Mesomelic dysplasia  Hypophosphatasia Dimples of the chin   Whistling face syndrome   Simosa craniofacial syndrome   Weaver syndrome Dimples of the shoulder (acromial dimples)   Autosomal dominant   18q deletion syndrome   Trisomy 9p   Russell-Silver syndrome   Popliteal pterygium syndrome Dimples of the sacrum   Bloom’s syndrome   Carpenter’s syndrome   Dubowitz’s syndrome   FG syndrome   Robinow’s syndrome   Smith-Lemli-Opitz syndrome   Spina bifida occulta   X-linked dysmorphic syndrome with mental retardation   Zellweger’s syndrome Dimples, other associations   Maternal rubella syndrome   Joubert’s syndrome   Caudal dysplasia sequence Dunnigan-Cobberling lipodystrophy – involves trunk, spares face JAAD 49:768–769, 2003 Ehlers-Danlos syndrome (periodontal EDS) – type VIII; periodontitis, marked skin fragility, over shins, pretibial bruising, cigarette paper scars, atrophy, wrinkling, skin thin and translucent with visible venous pattern, marfanoid habitus with triangular face, long nose,

thin philtrum; decrease types III and I collagen BJD 158:825–830, 2008; Ped Derm 24:189–191, 2007; Clin Pediatr 34:552–555, 1995; Clin Oral Investing 4:66–69, 2000; Birth Defects 13:85–93, 1983; JAAD 5:297–303, 1981 Elastoderma - cutis laxa-like changes JAAD 33:389–392, 1995 Elastosis perforans serpiginosa with pseudoxanthoma elasticumlike changes in Moya-Moya disease (bilateral stenosis and occlusion of basa intracranial vessels and carotid arteries) BJD 153:431–434, 2005 Epidermolysis bullosa – atrophic scarring; seen in multiple variants of epidermolysis bullosa including EBS Dowling-Meara; EBS, other generalized; EBS with muscular dystrophy, EBS with pyloric atresia; JEB, Herlitz type, JEB, non-Herlitz type, generalized; JEB non-Herlitz type, localized; JEB with pyloric atresia, JEB inversa; laryngo-­ onycho-­cutaneous syndrome; DDEB generalized; RDEB, severe generalized; RDEB, generalized other DDEB (acral) and RDEB (acral); DDEB (pretibial) and RDEB (pretibial), DEB pruriginosa; RDEB inversa; RDEB centripetalis JAAD 58:931–950, 2008 Epidermolysis bullosa, recessive dystrophic - symblepharon Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 135–151; dominant dystrophic – atrophic scars BJD 146:267–274, 2002; junctional EB, mitis type – ulcers, crusts, and atrophy; anonychia; pitted enamel of teeth; hyperkeratotic lesions of legs BJD 170:1056–1064, 2014; epidermolysis bullosa progressiva cigarette paper atrophy (junctional EB) JAAD 16:195–200, 1987; cicatricial junctional EB; generalized atrophic benign epidermolysis bullosa (GABEB) – atrophic scarring and follicular atrophy; atrophic nail beds and nails; COL17A1 mutations BJD 156:861–870, 2007; Dermatologica 176:83–90, 1988; epidermolysis bullosa superficialis – atrophic scarring, oral, conjunctival blisters AD 125:633–638, 1989; epidermolysis bullosa simplex with or without associated neuromuscular disease; thin or atrophic nails epidermolysis bullosa pruriginosa (DDEB) – nail dystrophy, atrophic skin with erosions, hypertrophic scarring, hypopigmentation, and linear scars BJD 172:778–781, 2015; AD 147:956–960, 2011; JAAD 56:S77–81, 2007; junctional epidermolysis bullosa of late onset (formerly junctional epidermolysis bullosa progressive) – loss of dermatoglyphic, waxy hyperkeratosis of dorsal hand, atrophic skin of lower leg, transverse ridging and enamel pits of teeth, nail atrophy, amelogenesis imperfect, hyperhidrosis, blisters on elbows, knees, and oral cavity BJD 164:1280–1284, 2011 Febrile ulceronecrotic Mucha-Habermann disease – atrophic scars JAAD 55:557–572, 2006; NJAAD 54:1113–1114, 2006; Ped Derm 22:360–365, 2005; BJD 152:794–799, 2005; JAAD 49:1142–1148, 2003; BJD 147:1249–1253, 2002; Ped Derm 8:51–57, 1991; Ann DV 93:481–496, 1966 Focal facial dermal dysplasia – scar-like depressions of pre-auricular regions of face JAAD 27:575–582, 1992 Follicular atrophoderma Ped Derm 25:112–113, 2008 Bazex-Dupre-Christol syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Ped Derm 25:112–113, 2008; Ped Derm 23:286–290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Atrophoderma vermiculata (basaloid follicular hamartoma syndrome) JAAD 39:853–857, 1998

Atrophic Lesions Chondrodysplasia punctata (Happle syndrome) Ann DV 121:297– 301, 1994   Rombo syndrome   Nevoid basal cell carcinoma syndrome Folliculitis ulerythematosa reticulata Generalized lipodystrophy Granuloma gluteale infantum with atrophic scars Clin Exp Dermatol 6:23–29, 1981 Inflammatory lipoatrophies   Connective tissue panniculitis   LE profundus  Morphea  Rothman-Makai   Weber Christian Non-inflammatory lipoatrophies   Annular atrophy of the ankles   Atrophic connective tissue panniculitis   Lipoatrophia annularis   Lipoatrophia semicircularis   Localized involutional lipoatrophy JAAD 35:523–528, 1996   Partial lipodystrophy with glomerulonephritis and complement abnormalities   Panatrophy of Gowers Junctional epidermolysis bullosa of late onset (skin fragility in childhood) - speckled hyperpigmentation of elbows; hemorrhagic bullae, teeth and nail abnormalities, oral blisters, disappearance of dermatoglyphs, palmoplantar keratoderma, small vesicles, atrophy of skin of hands BJD 169:714–716, 2013 Keratosis follicularis spinulosa decalvans Keratosis lichenoides chronica (Nekam’s disease) – reticulated keratotic papules, linear arrays, atrophy, comedo-­like lesions, prominent telangiectasia AD 144:405–410, 2008 Keratosis pilaris atrophicans Lateral facial clefts (macrostomia) – isolated; associated with Treacher-Collins syndrome, oculo-auriculo-vertebral spectrum, Nager acrofacial dysostosis, amniotic rupture sequence Syndromes of the Head and Neck, p. 709, 1990; J Laryngol Otol 87:309–313, 1973 Lichen planus – annular atrophic lichen planus AD 141:93–98, 2005; JAAD 25:392–394, 1991; atrophic variant JAAD 12:844–851, 1985; of breasts JAMA Derm 155:1187–1188, 2019; secondary anetoderma; atrophic nails Lichen sclerosus et atrophicus – wrinkled lesions, atrophic vulvar with shrinkage Cutis 67:249–250, 2001; Trans St John’s Hosp Dermatol Soc 57:9–30, 1971; lichen sclerosus of vulva and vagina – cobblestoned vagina, white atrophic plaques JAMA Derm 149:1199–1202, 2013 Linear focal elastosis (striae) – yellow linear bands of lower back JAAD 20:633–636, 1989 Lipoatrophia semicircularis – anterolateral thighs; band-like circular depression; lipoatrophy of ankles Cutis 80:464,477–478, 2008; BJD 105:591–593, 1981; JAAD 39:879–881, 1998 Lipoatrophy, acquired JAAD 60:519–521, 2009; JAAD 57:S85–87, 2007  associated with HIV disease – loss of subcutaneous fat from face, arms, legs; excess fat of neck and abdomen  acquired partial lipodystrophy – loss of fat of face, neck, arms, trunk, sparing legs  acquired generalized lipodystrophy –generalized loss of fat; tender subcutaneous nodules, autoimmune diseases   localized lipodystrophy

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Lipoatrophy, inherited JAAD 57:S85–87, 2007  Congenital generalized lipodystrophy type 1 (AGPAT2) – autosomal recessive; severe loss of adipose tissue from birth; type 2 (seipin) – autosomal recessive; severe lack of adipose tissue from birth, mild mental retardation, cardiomyopathy  Familial partial lipodystrophy, Dunnigan variety (LMNA) – autosomal dominant – loss of subcutaneous fat from arms, legs, trunk, sparing face and neck; appears at puberty  Familial partial lipodystrophy, PPAR gamma mutations (PPARgamma) – autosomal dominant; loss of subcutaneous fat from face, arms, legs  Mandibuloacral dysplasia, type A (LMNA) – autosomal recessive; skeletal anomalies; loss of subcutaneous fat of arms, legs, and trunk  Mandibuloacral dysplasia, type B (ZMPSTE24) – autosomal recessive; skeletal anomalies; generalized loss of fat; premature renal failure, progeroid features Lipodystrophia centrifugalis abdominalis infantilis – annular, atrophic patches and plaques Ped Derm 18:13–16, 2001; JAAD 11:203–209, 1984; AD 104:291–298, 1971 Lipodystrophia centrifugalis abdominalis infantilis -malformations of face, skull, hands Ped Derm 29:437–441, 2012; Ped Derm 19:365–367, 2002; hypopigmented and vulvar lesions Ped Derm 21:538–541, 2004; AD 104:291–298, 1971 Lipodystrophy Am J Med 108:143–152, 2000; JAAD 32:130–133, 1995  Congenital total lipodystrophy (congenital generalized lipodystrophy) (Berardinelli syndrome, Seip syndrome) – congenital total lipodystrophy; extreme muscularity and generalized loss of body fat from birth, acanthosis nigricans, acromegalic features, umbilical hernia, severe fasting and postprandial; hyperinsulinemia (fasting and postprandial), early onset diabetes mellitus or glucose intolerance, hypertriglyceridemia/low HDL-C level, hirsutism, clitoromegaly Cutis 70:65–69, 2002; J Clin Endocrinol Metab 85:1776–1782, 2000 J Clin Endocrinol Metab 85:1776–1782, 2000  Familial partial lipodystrophy of the limbs and lower trunk (Kobberling-Dunnigan syndrome, Dunnigan variety) – onset of lipoatrophy at puberty, extreme muscularity and lack of subcutaneous fat in all extremities, excess fat of face and neck, acanthosis nigricans, mild to moderate fasting or postprandial hyperinsulinemia, impaired glucose tolerance or diabetes mellitus after age 20 years, hypertriglyceridemia/low HDL-C levels Cutis 70:65–69, 2002; J Clin Endocrinol Metab 85:1776–1782, 2000  Familial partial lipodystrophy, mandibuloacral dysplasia variety – autosomal recessive; short stature, high pitched voice, mandibular and clavicular hypoplasia, dental anomalies, acro-osteolysis, stiff joints, cutaneous atrophy, alopecia, nail dysplasia Am J Med 108:143–152, 2000  Familial lipodystrophies, other – autosomal dominant; acromegalic features Am J Med 108:143–152, 2000  Acquired total lipodystrophy (acquired generalized lipodystrophy) (Lawrence-Seip syndrome) – extreme muscularity; generalized lack of fat during childhood or later, loss of subcutaneous fat from palms and soles, severe fasting or postprandial hyperinsulinemia, impaired glucose tolerance or diabetes mellitus, hypertriglyceridemia/low HDL-C levels; presence of other autoimmune diseases Cutis 70:65–69, 2002; J Clin Endocrinol Metab 85:1776–1782, 2000; AD 91:326–334, 1965  Acquired partial lipodystrophy ((partial cephalothoracic) progressive lipodystrophy, partial lipoatrophy, Barraquer-­Simons syndrome) – gradual onset loss of subcutaneous fat in cephalocaudal fashion from face, neck, trunk, and upper extremities in childhood, normal or increased fat of hips and lower extremities, proteinuria or mesangiocapillary glomerulonephritis, low C3 and

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presence of C3 nephritic factor, absence of insulin resistance; presence of other autoimmune diseases NEJM 350:1220–1234, 2004; JAAD 49:768–769, 2003; Cutis 70:65–69, 2002; J Clin Endocrinol Metab 85:1776–1782, 2000; JAAD 32:130–133, 1995   Generalized lipodystrophy JAAD 45:325–361, 2001   Pressure-induced lipodystrophy Am J Med 108:143–152, 2000   Partial lipodystrophy with renal disease - personal observation   Centrifugal lipodystrophy Am J Med 108:143–152, 2000  Lipodystrophia centrifugalis abdominalis infantilis – depression of skin of abdomen, groin, axillae due to loss of subcutaneous fat Ped Derm 29:308–310, 2012; AD 144:1651–1656, 2008; Ped Derm 21:538–541, 2004; BJD 140:1161–1164, 1999; JAAD 11:203–209, 1984; BJD 110:107–110, 1984; AD 104:291–298, 1971

Reactive perforating collagenosis – early childhood, precipitated by trauma; skin colored umbilicated papules; heal with hypopigmentation or scar AD 121:1554–1555, 1557–1558, 1985

Lipodystrophies, acquired and inherited NEJM 350:1220–1234, 2004

Spontaneous atrophic patches in extremely premature infants AD 132:671–674, 1996

Mid-dermal elastolysis (perifollicular atrophy) (atrophy and finely wrinkled skin) – well-circumscribed patches of fine wrinkling of trunk and proximal extremities of young women; perifollicular papular protrusions; persistent reticular erythema and fine wrinkling AD 146:1167–1172, 2010; Arch Dermatol Res 302:85–93, 2010; BJD 161:203–205, 2009; J Dtsch Dermatol Ges 7:68–69, 2009; BJD 156:1377–1379, 2007; JAAD 48:846–851, 2003; Cutis 71:312–314, 2003; J Cut Med Surg 4:40–44, 2000; BJD 132:487, 1995; JAAD 26:490–492, 1992; JAAD 26:169–173, 1992; AD 125:950–951, 1989; BJD 97:441–445, 1977

Striae distensae (striae atrophicans)

Reticulated atrophoderma Rudimentary meningocele and membranous aplasia cutis with hair collar AD 131:1427–31, 1995 Sclerotic panatrophy – may follow morphea or occur spontaneously; linear or annular or circumferential bands around limbs SHORT syndrome – short stature, hyperextensible joints, ocular depression, Reiger (ocular and dental) anomaly, teething delay, loss of subcutaneous fat of face, upper extremities, chest and abdomen Am J Med 108:143–152, 2000

Ulerythema ophryogenes Upper dermal elastolysis – yellow papules of neck with coarse furrows or wrinkles JAAD 51:165–185, 2004 Vermiculate atrophoderma – honeycomb atrophy

Panatrophy of Gowers – irregular sharply defined areas of atrophy; trunk and extremities

X-linked dominant ichthyosis (Happle’s syndrome) (ConradiHunermann syndrome) – chondrodysplasia punctata, ichthyosis, cataract syndrome; collodion baby or ichthyosiform erythroderma; Blaschko pattern of erythroderma and scaling; plantar hyperkeratosis; resolves with time to reveal swirls of fine scale, linear hyperpigmentation, follicular atrophoderma of arms and legs, cicatricial alopecia; skeletal defects with short stature severe autosomal rhizomelic type; X-linked recessive variant

Papular elastorrhexis – wrinkled skin colored papules Dermatology 205:198–200, 2002; Clin Exp Dermatol 27:454–457, 2002; JAAD 19:409–414, 1988; AD 123:433–434, 1987

PSYCHOCUTANEOUS DISEASES

Multiple benign annular creases of the extremities – deep creases around arms and legs Eur J Paediatr 138:301–303, 1982

Parakeratosis variegata – reticulated and atrophic Dermatology 201:54–57, 2000; BJD 137:983–987, 1997; Dermatology 190:124– 127, 1995 Partial face-sparing lipodystrophy (Kobberling-Dunnegan syndrome) AD 132:223–228, 1996; JAAD 32:130–133, 1995 Partial lipodystrophy (Barraquer-Simons disease) – disappearance of facial fat; upper half of body (Seir-Mitchell type); hypertrophy of lower part of body (Laignel-Lavastine and Viard type) Q J Med 41:343–354, 1972; association with hypocomplementemia (C3 nephritic factor) NEJM 294:461–465, 1976 Perifollicular atrophoderma Perifollicular macular atrophy (perifollicular elastolysis) – gray-white follicular papules or finely wrinkled round areas of atrophy with central hair follicle; upper trunk, neck, earlobes, arms JAAD 51:165–185, 2004; BJD 83:143–150, 1970 Perioral pigmented follicular atrophoderma BJD 139:713–718, 1998 Periumbilical pseudoxanthoma elasticum Pohl-Pinkus constriction of hair BJD 79:43–50, 1967 Poikiloderma vasculare atrophicans - personal observation Porokeratosis - of Mibelli – central atrophy AD 122:586–587, 1986; disseminated superficial (actinic) porokeratosis Int J Dermatol 34:71–72, 1998; BJD 123:249–254, 1996; Cutis 42:345–348, 1988; palmoplantar porokeratosis JAAD 21:415–418, 1989 Primary atrophy of the lip - personal observation Prurigo nodularis - anetodermic prurigo nodularis JAAD 25:437– 442, 1991 Psoriasis – absence of psoriasis in polio-afflicted leg BJD 171:429– 431, 2014

Delusions of parasitosis – white atrophic scars with erosions and ulcers NEJM 371:2115–2123, 2014 Factitial traumatic panniculitis mimicking acrodermatitis atrophicans JAAD 13:988–994, 1985 Neurotic excoriations – atrophic scars Compr Psychiatry 27:381– 386, 1986

SYNDROMES Achenbach’s syndrome (paroxysmal hematoma of the finger) – mimics bruising or steroid atrophy; BJD 132:319, 1995 Acquired partial lipodystrophy (progressive lipodystrophy, partial lipodystrophy, Barraquer-Simons syndrome) – gradual-onset loss of subcutaneous fat from face, neck, trunk, and upper extremities during childhood; normal or excess amount of subcutaneous fat in hips and lower extremities, proteinuria or mesangiocapillary glomerulonephritis, low C3, presence of C3-nephritic factor, no insulin resistance; presence of other autoimmune diseases; anti-phospholipid and anticardiolipin antibodies Ped Derm 27:504– 508, 2010; Lab Med 36:546–549, 2005; Medicine (Balt) 83:18–34, 2004; NEJM 350:1220–1234, 2004; JAAD 49:768–769, 2003; J Clin Endocrinol Metab 85:1776–1782, 2000; JAAD 32:130–133, 2000 Acrocephalopolysyndactyly Acrogeria – atrophy and mottled hyperpigmentation of acral skin; thick or thin nails, micrognathia, atrophic tip of nose BJD 151:497– 501, 2004; BJD 142:178–180, 2000; BJD 103:213–223, 1980; Arch Dermatol Syphiligr 181:571–583, 1941 Adams-Oliver syndrome - congenital scalp ACC and amniotic bands with reduction of terminal phalanges of fingers and toes (terminal transverse limb defects); occasionally severe bony defects with

Atrophic Lesions absent hands, feet, or lower legs; bony abnormalities of cranium; cutis marmorata telangiectatica congenita, severe growth retardation, aplasia cutis congenita of knee, short palpebral fissures, dilated scalp veins, simple pinnae, skin tags on toes, hemangioma, undescended testes, supernumerary nipples, hypoplastic optic nerve, central nervous system and congenital heart defects Ped Derm 25:115–116, 2008; Ped Derm 24:651–653, 2007; BJD 157:836–837, 2007; Am J Med Genet 136A:269–274, 2005; Plast Reconstr Surg 100:1491–1496, 1997; Clin Genet 47:80–84, 1995; Int J Dermatol 32:52–53, 1993; Eur J Pediatr 126:289–295, 1977; JAAD 56:541–564, 2007; J Hered 36:3–7, 1945 Aesop syndrome – extensive red violaceous skin patch or plaque of chest overlying a solitary bone plasmacytoma with regional adenopathy; dermal mucin and vascular hyperplasia (mucinous angiomatosis) JAAD 55:909–910, 2006; atrophic plaque Medicine 82:51–59, 2003 Albright’s hereditary osteodystrophy (pseudohypoparathyroidism) – absence of fourth knuckles of hands and feet; atrophic pink patches of neck with striations containing white papules (subcutaneous ossification); white papules of trunk and ear; dry, rough keratotic puffy skin; short stature, obesity, frontal bossing, depressed nasal bridge; brachydactyly with dimples over 4th and 5th metacarpal bones; mutation in GNAS1 gene NEJM 367:2527, 2012; BJD 162:690–694, 2010; Ergeb Inn Med Kinderheilkd 42:191–221, 1979; Endocrinology 30:922–932, 1942 Amniotic band syndrome Int J Dermatol 27:312–4, 1988 Anhidrotic ectodermal dysplasia Anonychia with ectrodactyly Antiphospholipid antibody syndrome – anetoderma JAAD 60:1–20, 2009 AREDYLD syndrome – ectodermal dysplasia, lipoatrophy, diabetes, mellitus, amastia Am J Med Genet 44:374–377, 1992; Am J Med Genet 16:29–33, 1983 Ascher’s syndrome – periorbital edema; edema of lips, double lip, blepharochalasis AD 139:1075–1080, 2003; Klin Monatsbl Augenheilkd 65:86–97, 1920 Ataxia telangiectasia - lipoatrophy JAAD 42:939–969, 2000; JAAD 10:431–438, 1984; atrophic plaque of cutaneous granuloma of ataxia telangiectasia AD 134:1145–1150, 1998; atrophy of skin Baraitser syndrome (premature aging with short stature and pigmented nevi) – lack of facial subcutaneous fat, fine hair, hypospadias, dental abnormalities, hepatomegaly J Med Genet 25:53–56, 1988 Barber-Say syndrome – autosomal dominant or X-linked; generalized hypertrichosis, dysmorphic facies (bilateral ablepharon, ectropion of lower eyelids, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Am J Med Genet 73:366–367, 1997; Am J Med Genet 47:20–23, 1993; Syndrome Ident 8:6–9, 1982 Bart’s syndrome – aplasia cutis congenita of the legs with dystrophic epidermolysis bullosa Bazex-Dupre-Christol syndrome (X-linked dominant) - milia and comedo-like papules, congenital hypotrichosis, anhidrosis, X-linked dominant, follicular (vermiculate) atrophoderma of the face, elbows and hands, hypohidrosis, basal cell nevi and basal cell carcinomas, trichoepitheliomas, pinched nose, keratosis pilaris, scrotal tongue, joint hypermobility; UBE 2A gene JAAD 74:437–451, 2016; Ped Derm 28:727–728, 2011; Ped Derm 25:112–113, 2008; Ped Derm 23:149–151, 2006; BJD 153:682–684, 2005; Dermatol Surg

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26:152–154, 2000; Ped Derm 16:108–110, 1999;JAAD 39:853–857, 1998; AD 130:337–342, 1994; Hautarzt 44:385–391, 1993; J Cutan Pathol 18:20–27, 1991; Ann Dermatol Syphilgr (Paris) 93:241–254, 1966; Bull Soc Franc Derm Syph 71:206, 1964 Beckwith-Wiedemann syndrome (Exomphalos-MacroglossiaGigantism) (EMG) syndrome – autosomal dominant; zosteriform rash at birth, circular depressions of helices, exomphalos, macroglossia, visceromegaly, facial nevus flammeus and gigantism; earlobe grooves, punched-out depressions of posterior pinna JAAD 37:523–549, 1997; Am J Dis Child 122:515–519, 1971 Bencze syndrome – hemifacial atrophy with esotropia, amblyopia, and submucous cleft palate Clin Genet 16:301–304, 1979 Berlin syndrome – fine wrinkling around the eyes and mouth (similar to Christ-Siemens ectodermal dysplasia); no vellus hairs; mottled pigmentation and leukoderma, flat saddle nose, thick lips, stunted growth, bird-like legs, mental retardation Dermatologica 123:227– 243, 1961 Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; translucent skin-colored papules (non-caseating granulomas) of trunk and extremities; may resolve with pitted scars with follicular atrophoderma; with uveitis, synovitis, arthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints) mutations in NOD2 (nucleotide-binding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996 Bloom’s syndrome – decreased subcutaneous fat JAAD 75:855– 870, 2016 Branchio-oculo-facial syndrome - linear atrophic patches of neck, ears, eyes, mouth; hemangiomatous aplastic skin overlying branchial or supraauricular defects; atrophic neck lesions Ped Derm 29:383–384, 2012; Ped Derm 12:24–27, 1995; Am J Med Genet 56:42–59, 1995 Buschke-Ollendorff syndrome – depressed indurated plaque with elastorrhexis Ped Derm 37:385–386, 2020 Carbohydrate-deficient glycoprotein syndrome – emaciated appearance; lipoatrophy over buttocks; lipoatrophic streaks extend down legs; high nasal bridge, prominent jaw, large ears, inverted nipples, fat over suprapubic area and labia majora, fat pads over buttocks; hypotonia Cardio-facio-cutaneous syndrome Dev Med Child Neurol 35:727– 732, 1993 Charcot-Marie-Tooth disease (axonal peripheral neuropathy) – atrophy of calves and interosseous muscles of hands; associated with Unna-Thost palmoplantar keratoderma BJD 177:284–286 2017 Chromosome 16–18 defect – large scalp defects; scalp arteriovenous malformation with underlying bony defect CLOVES syndrome (congenital lipomatous overgrowth with vascular, epidermal, and spinal and skeletal abnormalities; lipoatrophy – somatic activating mutation in PIK3CA Ped Derm 34:735–736, 2017; JAAD 68:885–896, 2013; Am J Hum Genet 90:1108–1115, 2012 Cockayne’s syndrome (cachectic dwarfism) – autosomal recessive; thin skin, dry hair, anhidrosis, short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes (enophthalmos with loss of periorbital fat), lipoatrophy of temples; canities, nail dystrophy, hair loss, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects, demyelination JAAD 75:873–882, 2016; Ped Derm 20:538–540, 2003; J Med Genet 18:288–293, 1981

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Congenital generalized lipodystrophy – autosomal recessive; APGAT2 (1-acylglycerol-3-phophate-O-­­acyltransferase2 Ped Derm 27:504–508, 2010 Congenital ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis Am J Med Geneet 13:186–189, 1998 Conradi-Hunermann syndrome (chondrodysplasia punctata X-linked dominant) – linear and whorled hyperkeratosis, follicular atrophoderma of forearms in Blaschko distribution; linear atrophic lesions with follicular plugging of scalp; cicatricial alopecia of scalp; patchy patterned alopecia, generalized xerosis; cataracts, chondrodysplasia punctata; asymmetric shortening of long bones epiphyseal stippling, short stature, short limbs, kyphoscoliosis, craniofacial abnormalities); short arms and legs; cataracts X-linked; mutation in emopamil binding protein (EBP) Ped Derm 31:493–496, 2014; BJD 160:1335–1337, 2009; Curr Prob in Derm VII:143–198, 1995; AD 121:1064–1065, 1985; ichthyotic and psoriasiform lesions (Blaschko hyperkeratotic scaling), nail defects, cicatricial alopecia, follicular pitted scars, skeletal anomalies JAAD 33:356–360, 1995; Hum Genet 53:65–73, 1979; neonatal transient scaly plaques of limbs, trunk, and scalp; scaly rash disappears in months leaving hypo- or hyperpigmented streaks with follicular atrophoderma and patchy scarring alopecia; CDPX2 – X-linked lethal in males; X-linked dominant (mosaic for emopamil-binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309–1313, 2012; BJD 157:1225–1229, 2007; Eur J Dermatol 10:425–428, 2000; Hum Genet 53:65–73, 1979 Cornelia de Lange (Brachmann-de Lange) syndrome – hypoplastic epidermal ridges of palms, soles, fingers, and toes; single palmar crease, hypoplastic nipples and umbilicus, umbilical hernia Syndromes of the Head and Neck, p.303, 1990; generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, posterior neck, and arms, low set ears, arched palate, antimongoloid palpebrae; congenital eyelashes; xerosis, especially over hands and feet, nevi, facial cyanosis, lymphedema Ped Derm 24:421–423, 2007; JAAD 56:541–564, 2007; JAAD 48:161–179, 2003; JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993 Curry-Jones syndrome – linear hypo- or hyperpigmented lesions, palmoplantar pitting, streaks of atrophy, hypertrichosis, trichoblastomas and nevus sebaceous, polydactyly or preaxial polysyndactyly, dysmorphic facies, macrocephaly, microcephaly, dental anomalies, craniosynostosis, anal stenosis, myofibromas and smooth muscle hamartomas, medulloblastomas, cerebral malformations (agenesis of corpus callosum), developmental delay, cataracts, microphthalmia, coloboma, glaucoma, cryptorchidism; mutation in SMOc.1234C>T BJD 182:212–217, 2020; Clin Dysmorphol 4:116–129, 1995 DeBarsy syndrome – autosomal recessive progeroid syndrome; lax wrinkled skin; cloudy corneas, mental retardation, pseudoathetoid movements, synophrys, pinched nose, thin skin, lack of subcutaneous tissue, sparse hair Ped Derm 19:412–414, 2002; Eur J Pediatr 144:348–354, 1985 Delleman-Oorthuys syndrome – oculocerebrocutaneous syndrome – membranous aplasia cutis, eyelid tag, periorbital tags, facial tags, orbital cysts, focal punched-out skin defects of the ala nasi, cerebral malformations, developmental delay AD 147:345– 350, 2010; Textbook of Neonatal Dermatology, p. 127, 2001; Clin

Dysmorphol 7:279–283, 1998; Clin Genetics 19:191–198, 1981; pedunculated facial papules and atrophic patches of neck; accessory tragi and aplasia cutis congenita AD 147:345–350, 2011; J Med Genet 25:773–778, 1988 Dermatopathia pigmentosa retularis – autosomal dominant, reticulate hyperpigmentation of trunk, onychodystrophy, alopecia, oral hyperpigmentation, punctate hyperkeratosis of palms and soles, hypohidrosis; atrophic macules over joints with hypertrophic scarring Semin Cut Med Surg 16:72–80, 1997; AD 126:935–939, 1990; Hautarzt 6:262, 1960 Didymosis aplasticosebacea – aplasia cutis congenita in a nevus sebaceus (Schimmelpenning syndrome); coloboma of eyelid Ped 24:514–516, 2007 Diffuse and macular atrophic dermatosis – generalized poikilodermatous prematurely aged (sun-damaged) appearance Clin Exp Dermatol 5:57–60, 1980 Digitocutaneous dysplasia – X-linked dominant; digital fibromas, atrophic plaques with appearance of hyperpigmentation, metacarpal and metatarsal disorganization with resultant brachydactyly and clinodactyly, dysmorphic features including frontal bossing, broad nasal root, telecanthus and epicanthal folds, conical teeth, dental fissures, hypodontia, accessory gingival frenula, enamel hypoplasia JAAD 56:S6–9, 2007 Dowling-Degos syndrome (reticulated pigmented anomaly of the flexures) – pitted atrophic scars at corners and around mouth (perioral pits), reticulated pigmentation of axillae, groin, and other intertriginous areas, freckles of vulva, comedo-like lesions JAAD 57:327–334, 2007; BJD 147:568–571, 2002; JAAD 40:462–467, 1999; Semin Cut Med Surg 16:72–80, 1997; Clin Exp Dermatol 9:439–350, 1984; AD 114:1150, 1978; acantholytic variant (Galli-­Galli disease) JAAD 45:760–763, 2001; JAAD 24:888–892, 1991; Hautarzt 33:378–383, 1982; reticulated pigmentation of the vulva and perianal skin AD 148:113–118, 2012 Dunnigan partial lipodystrophy – autosomal dominant; loss of fat from extremities with face and neck spared; mutation in nuclear lamina proteins A and C (LMNA) NEJM 350:1220–1234, 2004; Ped Derm 27:504–508, 2010 Dunnigan syndrome autosomal recessive; acanthosis nigricans, decreased subcutaneous fat, enlarged clitoris, insulin-resistant diabetes mellitus, thickened nails, pineal hyperplasia, premature eruption of teeth, macrodontia, enlarged filiform and fungiform papillae of the tongue J Med Genet 23:128–130, 1986 Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) – Xq28; leukoplakia and nail atrophy; DKC1 mutation; defective telomere maintenance Ped Derm 28:464–466, 2011; J Med Genet 33:993– 995, 1996; Dermatol Clin 13:33–39, 1995; BJD 105:321–325, 1981; thin or atrophic nails Ehlers-Danlos syndrome – EDS I, II - atrophic fish-mouth and cigarette paper scarring; redundant folds around eyes; EDS II with features of cutis laxa Cutis 82:242–248, 2008; type IV – acrogeric skin type; prominent eyes; dry wrinkled pigmented skin of arms and legs; pinched nose; lobeless ears; thin translucent skin with bruising; joint hyperextensibility; abnormal type III collagen and defect in type III collagen synthesis; spontaneous vascular rupture; BJD 163:704– 710, 2010; type VII – lax facial skin giving chubby appearance J Med Genet 24:698–701, 1987; type VI – blue sclerae, scleral fragility, joint hypermobility, skin hyperextensibility, easy bruising, atrophic scarring, marfanoid habitus, scoliosis, neonatal hypotonia, arterial dissection; type VIII – autosomal dominant; skin fragility, abnormal scarring, severe early periodontitis with loss of adult dentition by end of third decade; cigarette paper scars of shin; marfanoid habitus (tall, long limbs, arachnodactyly); triangular face, prominent eyes, thin nose, prematurely aged appearance, thin skin

Atrophic Lesions with prominent veins, no joint hypermobility, easy bruising, blue sclerae JAAD 55:S41–45, 2006; Heritable Disorders of Connective Tissue, 4th Ed, St. Louis: Mosby 1972; Ehlers-Danlos syndrome type VIII – gingivitis, atrophic translucent hyperpigmented skin of shins Ped Derm 24:189–191, 2007; Clin Pediatr 34:552–555, 1995 Ellis van Creveld syndrome - thin or atrophic nails Familial mandibuloacral dysplasia (craniomandibular dermatodysostosis) – atrophy of skin over hands and feet with club shaped terminal phalanges and acro-osteolysis, mandibular dysplasia, delayed cranial suture closure, short stature, prominent eyes and sharp nose BJD 105:719–723, 1981; Birth Defects x:99–105, 1974 Familial partial lipodystrophy (Kobberling-Dunning syndrome, Dunnigan variety) – extreme muscularity and lack of subcutaneous fat in all extremities with onset at puberty; normal at birth; excess adipose tissue of face and neck, acanthosis nigricans, post-prandial hyperinsulinemia, diabetes mellitus after age 20, hypertriglyceridemia and pancreatitis J Clin Endocrinol Metab 85:1776–1782, 2000 Finlay-Marks syndrome (scalp-ear-nipple syndrome) – nipple or breast hypoplasia or aplasia, aplasia cutis congenita of scalp, abnormal ears and teeth, nail dystrophy, syndactyly, reduced apocrine secretion Focal facial dermal dysplasia; bitemporal atrophy with scar-like atrophic macules on one or both temples (Brauer’s syndrome); type I is AD; type II is AR JAAD 25:389–391, 1991; JAAD 18:1203–1207, 1988 Flynn-Aird syndrome - atrophy of shins and dorsae of feet, ulceration, alopecia, dental caries J Neurol Sci 2:161–182, 1965 Focal facial dermal dysplasia type IV – atrophic scars of face Ped Derm 36:251–252, 2019 Follicular atrophoderma  Bazex-Dupre-Christol syndrome, X-linked dominant AD 130:337– 342, 1994  Conradi-Hunermann syndrome JAAD 21:248–256, 1989, Ped Derm 15:299–303, 1998; Hum Genet 53:65–73, 1979  Happle syndrome - X-linked dominant chondrodysplasia puntata - streaks Ped Derm 13:1–4, 1996   Rasmussen’s syndrome AD 111:610–614, 1975   Rombo syndrome 4p (-) syndrome – aplasia cutis, mental retardation, deafness, seizures, ocular abnormalities Fragile X syndrome – fine skin, hyperextensible joints, flat feet Lancet 338:289–292, 1991 Geroderma osteodysplastica (Bamatter syndrome) (osteodysplastic geroderma) – autosomal recessive; short stature, cutis laxa-like changes with drooping eyelids and jowls (sad characteristic facies), osteoporosis and skeletal abnormalities; lax wrinkled, atrophic skin and hyperextensible joints, osteoporosis, growth retardation Ped Derm 23:467–472, 2006; Ped Derm 16:113–117, 1999; Am J Med Genet 3:389–395, 1979; Hum Genet 40:311–324, 1978; Ann Paediatr 176:126–127, 1950 Gobello syndrome –systematized linear velvety orthokeratotic nevus, hypertrichosis and follicular hyperkeratosis, bony defects with hemihypoplasia of limbs Dermatology 201:51–53, 2000 Goldenhar syndrome (oculo-auriculo-vertebral syndrome) – facial hemiatrophy; accessory tragi (preauricular tags); ocular lipodermoids, epibulbar dermoids; multiple vertebral anomalies, gastrointestinal anomalies, microphthalmia, anophthalmia, colobomata, genital anomalies, micrognathia, microtia, cleft lip/palate, hemifacial microsomia, urologic anomalies, cardiac anomalies, pulmonary anomalies Ped Derm 24:657–658, 2007; JAAD 50:S11–13, 2004;

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Syndromes of the Head and Neck, p. 641–649, 1990; aplasia cutis congenita JAAD 50:S11–13, 2004 Goltz’s syndrome (focal dermal hypoplasia) – asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberry-like papillomas of lips, perineum, acrally, at perineum, buccal mucosa; xerosis; hypopigmented atrophic macules, Blaschko-esque hyperpigmentation, yellow nodulaes of hand, oligodontia, wide-spaced teeth, cleft hand, syndactyly, mammary hypoplasia, scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones; thin or atrophic nails JAMA Derm 152:209–210, 2016; AD 148:85–88, 2012; AD 143:109–114, 2007; ) Nature Genet 39:836–838, 2007; AD 128:1108–1111, 1992 JAAD 25:879–881, 1991; AD 86:708–717, 1962; aplasia cutis congenita AD 145:218–219, 2009; male mosaic Goltz’s syndrome; blaschko-linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011; unilateral focal dermal hypoplasia, unilateral – PORCN gene mutation; PORCN encodes O-acyltransferase involved in palmitoylation and secretion of Wnt signaling proteins important in embryonic tissue development, fibroblast proliferation and osteogenesis AD 148:85–88, 2012; focal dermal hypoplasia, morning glory anomaly, and polymicrogyria – swirling pattern of hypopigmentation, papular hypopigmented and herniated skin lesions of face, head, hands, and feet, basaloid follicular hamartomas, mild mental retardation, macrocephaly, microphthalmia, unilateral morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly Am J Med Genet 124A:202–208, 2004Granddad syndrome - Am J Hum Gen 45 (suppl)A53, 1989 H syndrome – autosomal recessive; Arabic Palestinian population; gluteal lipoatrophy; hyperpigmentation, phalangeal flexion contractures, hearing loss, short stature, diabetes mellitus, lymphadenopathy, hypertrichosis, hepatosplenomegaly, heart anomalies, hypogonadism, micropenis, hallus valgus, hyperpigmentation induration and hypertrichosis of inner thighs and shins, chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, facial telangiectasia, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 JAAD 70;80–88, 2014 Haber’s syndrome - rosacea-like acneiform eruption with erythema, telangiectasia, prominent follicles, comedones, small papules, atrophic pitted scars; with keratotic plaques of the trunk and extremities BJD 160:215–217, 2009; AD 103:452–455, 1971; BJD 77:1–8, 1965 Haim-Munk syndrome – autosomal recessive; mutation in cathepsin C gene (like Papillon-Lefevre syndrome); atrophic nails, palmoplantar keratoderma, scaly red patches on elbows, knees, forearms, shins, gingivitis with destruction of periodontium, onychogryphosis, arachnodactyly, recurrent pyogenic infections BJD 152:353–356, 2005 Hallermann-Streiff syndrome - central facial atrophy and telangiectasia Ped Derm 13:255–257, 1996; atrophic alopecia Clin Exp Dermatol 14:250–252, 1989 Happle syndrome (X-linked dominant chondrodysplasia punctata) – scalp dermatitis at birth; Blaschko hyperkeratoses, follicular atrophoderma, cicatricial alopecia Ped Derm 18:442–444, 2001 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifesta-

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tion, developmental delay, optic glioma or meningioma, cataracts, microphthalmia , coloboma; mutation in SMOc.1234C>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hereditary acrokeratotic poikiloderma Hereditary focal transgressive palmoplantar keratoderma – autosomal recessive; hyperkeratotic lichenoid papules of elbows and knees, psoriasiform lesions of scalp and groin, spotty and reticulate hyperpigmentation of face, trunk, and extremities, alopecia of eyebrows and eyelashes BJD 146:490–494, 2002 Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa with generalized cutaneous atrophy, corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005 Hereditary perioral pigmented follicular atrophoderma associated with milia and epidermoid cysts BJD 139:713–718, 1998 Hereditary sclerosing poikiloderma Huriez syndrome – autosomal dominant; palmoplantar keratoderma with sclerodactyly and scleroatrophy of distal extremities with nail changes (hypoplasia, longitudinal ridging, distal splitting); hypohidrosis, poikilodermatous changes of nose, flexion contractures of fingers AD 146:1419–1424, 2010; TIG 13:229, 1997 Hutchinson-Gilford syndrome (progeria) - loss of subcutaneous tissue with atrophic wrinkled skin, hyper and hypomelanosis, alopecia, mid-facial cyanosis around mouth and nasolabial folds, decreased sweating, sclerodermoid changes, cobblestoning of soft pebbly nodules JAMA Derm 150:197–199, 2014; Am J Med Genet 82:242–248, 1999; earliest initial changes include alopecia, sclerodermoid changes of chest and abdomen, prominent superficial veins and dyspigmentation JAMA Derm 150:197–198, 2014 Hypertrichosis, pigmentary retinopathy, and facial anomalies – lipoatrophy of buttocks Am J Med Genet 62:386–390, 1996 Hypohidrotic ectodermal dysplasia - facial wrinkling; bilateral amastia BJD 171:671–673, 2014 Ichthyosis cerebriformis – keratotic plugs, depressions, thick skin, palmoplantar keratoderma JAAD 58:505–507, 2008 Ichthyosis, follicular atrophoderma, eyebrow hypotrichosis, woolly hair BJD 147:604–606, 2002; Am J Med Genet 75:186–189, 1998 Incontinentia pigmenti – pale atrophic hairless patches in stage 4 JAAD 64:508–515, 2011; AD 139:1163–1170, 2003; JAAD 47:169–187, 2002; atrophic vermiculate scarring of legs Atlantic Derm Society Meeting, 2000; Dermatol 191 (2):161–163, 1995; thin or atrophic nails; foreshortened hand Ped Derm 26:83–86, 2009 Job’s syndrome (hyper IgE syndrome) – autosomal dominant or sporadic; atrophoderma vermiculatum; coarse facial features with broad nose, rough thickened skin with prominent follicular ostia; papular and papulopustular folliculitis-like eruptions; oral candidiasis; chronic paronychia; cold abscesses of neck and trunk; otitis media common; mutation in STAT3 (transcription 3 gene activator and signal transducer JAAD 65:1167–1172, 2011 Johanson-Blizzard syndrome – small stellate defects of frontal scalp and membranous aplasia cutis, dwarfism, mental retardation, deafness, hypothyroidism, pancreatic insufficiency, midline skin dimples or defects J Med Genet 19:302–303, 1981 Juvenile hyaline fibromatosis (Murray-Puretic-Drescher syndrome) – autosomal recessive; gingival fibromatosis, multiple subcutaneous tumors, sclerodermiform atrophy, osteolytic skeletal lesions, recurrent suppurative infections, flexural joint contractures, stunted growth, early death Ped Derm 18:400–402, 2001 Kabuki makeup syndrome – pre-auricular dimple/fistula, short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower

eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170– 173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849– 850, 1984; J Pediatr 99:565–569, 570–573, 1981 Keratosis follicularis spinulosa decalvans – conjunctivitis; keratosis pilaris, follicular atrophoderma, facial erythema, scarring alopecia, ulerythema oophyrogenes, photophobia JAAD 58:499–502, 2008; Arch Dermatol Syphilol 151:384–387, 1926 Kindler’s syndrome - diffuse atrophy or cigarette paper atrophy of dorsal hands; atrophied gingivae; atrophic nail plates; Kindler’s syndrome – acral blistering at birth; progressive poikiloderma; cigarette paper atrophy of hands and feet (scleroatrophy), atrophied gingiva, photosensitivity JAMA 306:767–768, 2011; BJD 160:1119–1122, 2009; BJD 160:233–242, 2009; BJD 159:1192– 1196, 2008; BJD 158:1375–1377, 2008; BJD 157:1252–1256, 2007; AD 142:1619–1624, 2006; AD 142:620–624, 2006; Ped Derm 23:586–588, 2006; Actas Dermosifiliogr 96:677–680, 2005; AD 140:939–944, 2004; BJD 144:1284–1286, 2001; JAAD 46:447–450, 2001; AD 132:1487–1490, 1996; AD 133:1111–1117, 1997; Ped Derm 6:82–90, 1989; Ped Derm 6:91–101, 1989; BJD 66:104–111, 1954 Klippel-Trenaunay-Weber syndrome – atrophy of limb BJD 156:391–3392, 2007; Rontgenpraxis 52:312–316, 2000; Clin Exp Dermatol 13:237–239, 1988; venous malformation, arteriovenous fistula, or mixed venous lymphatic malformation Br J Surg 72:232– 236, 1985; Arch Gen Med 3:641–672, 1900 Koraxitrachitic syndrome – self-healing collodion baby with residual dappled atrophy Am J Med Genet 86:454–458, 1999 Lenz-Majewski syndrome – loose, wrinkled atrophic skin of hands with short digits and partial syndactyly Radiology 149:129–131, 1983 Lipoid proteinosis – crusted erosions leading to linear pitted scars Ped Derm 18:21–26, 2001 Leprechaunism (Donohue’s syndrome) – decreased subcutaneous tissue and muscle mass (lipoatrophy), characteristic facies, severe intrauterine growth retardation, broad nose, low set ears, hypertrichosis of forehead and cheeks, loose folded skin at flexures, gyrate folds of skin of hands and feet; breasts, penis, clitoris hypertrophic Endocrinologie 26:205–209, 1988 Lipodystrophy associated with mandibuloacral dysplasia – bird-like facies, acro-osteolysis, mottled cutaneous pigmentation, dental abnormalities, skin atrophy, alopecia J Clin Endocrinol Metab 87:776–785, 2002 Lipoid proteinosis – pock-like annular scars Ped Derm 19:359–362, 2002; Ped Derm 18:21–26, 2001; weathered appearance of face; Acta Paediatr 85:1003–1005, 1996; JAAD 27:293–297, 1992 Loeys-Dietz syndrome – autosomal dominant; TGFBR1 or TGFBR2 (transforming growth factor beta receptor genes); marfanoid habitus, delicate triangular face, multiple facial milia, velvety and translucent skin, easy bruising, varicose veins, atrophic scars, malar hypoplasia, retrognathia, craniosynostosis, hypertelorism, cleft lip and palate, bifid uvula, malar hypoplasia, blue sclerae, arachnodactyly, joint laxity, pectus deformities, scoliosis, camptodactyly, high arched palate, aortic root aneurysm and dissection, arterial tortuosity AD 147:223–226, 2011; JAAD 59:1050–1063, 2008; JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005

Atrophic Lesions LUMBAR syndrome – patch of hypo- and hyperpigmentation with atrophic macule Ped Derm 37:78–85, 2020 Macrostomia, ectropion, atrophic skin, hypertrichosis and growth retardation Mandibuloacral dysplasia – acral poikiloderma over hands and feet, subcutaneous atrophy Am J Med Genet 95:293–295, 2000; Clin Genet 26:133–138, 1984 Marfan’s syndrome – progressive striae JAAD 64:290–295, 2011; Int J Dermatol 28:291–299, 1989 Marshall’s syndrome - Sweet’s syndrome followed by acquired cutis laxa AD 131:1175–1177, 1995 MASS phenotype – atrophic skin patches (anetodermas) (prolapsed mitral valve, myopia, aortic root enlargement, skeletal and skin manifestations) (Marfan’s-like syndrome) – slender habitus, loss of subcutaneous fat JAMA Derm 150:885–889, 2014; JAMA Derm 262:523–528, 1989 Mendenhall’s syndrome - pineal hyperplasia, insulin resistant diabetes mellitus, lipodystrophy Mendes da Costa syndrome (dystrophia bullosa, typus maculatus) – X-linked recessive; tense bullae, alopecia, coarse reticulated hyperpigmentation of face and extremities with atrophy, mental retardation Acta DV (Stockh) 18:265, 1937 Metageria Metaphyseal dysplasia, anetoderma, optic atrophy Microphthalmia with linear skin defects syndrome (MLS syndrome) (microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome) – X-linked dominant; atrophic Blaschko linear scars of face and neck; linear red atrophic skin (resembles aplasia cutis) Am J Med Genet 124A:202–208, 2004; Am J Med Genet 49:229–234, 1994 Multiple benign annular creases of the extremities Multiple follicular hamartomas with sweat gland and sebaceous differentiation, vermiculate atrophoderma, milia, hypotrichosis, and late development of basal cell carcinomas JAAD 39:853–857, 1998 Nail-patella syndrome – hypoplasia of distal phalanges Ped Derm 19:454–456, 2002; thin or atrophic nails Nestor-Guillermo syndrome – secondary laminopathy; failure to thrive with onset at age 2; atrophic skin with senile shin spots, generalized lipoatrophy, prominent superficial vein, osteoporosis, scoliosis “chronic progeria”, longer survival; mutation in BANF1 Nucleus 9:249–260, 2018 Neurofibromatosis type 1 - pseudoatrophic macules (neurofibroma presenting as gray-white atrophic patch) JAAD 61:1–14, 2009; Ped Derm 26:231–232, 2009; Cutis 57:100–102, 1996; BJD 112:435– 441, 1985; AD 118:577–581, 1982; congenital reddish neurofibromatous dermal hypoplasia with follicular papules Cutis 68:253–256, 2001 Neutrophilic dermatosis (pustular vasculitis) of the dorsal hands – variant of Sweet’s syndrome – atrophic scars AD 138:361–365, 2002 Nevoid basal cell carcinoma syndrome with type 2 mosaicism – Blaschko-esque atrophy, Blaschko-esque pits of palms; linear papules of foot; white papules and plaques; segmental hyper- and hypopigmented patches BJD 169:1342–1345, 2013 Nicolau-Balus syndrome - vermiculate atrophoderma of cheeks, eruptive syringomas and milia on trunk and extremities Nijmegen breakage syndrome – autosomal recessive; microcephaly, growth retardation, chromosomal instability, and combined immunodeficiency; pink to red-brown firm papules and plaques with sclerosis and atrophy, clinodactyly, syndactyly, vitiligo, café au lait macules Ped Derm 27:285–289, 2010

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Noonan’s syndrome - ulerythema ophryogenes Oculocerebrocutaneous syndrome –orbital cyst, cerebral malformations, skin tags, focal hypoplasia skin lesions Am J Ophthalmol 99:142–148, 1985; regional skin hypoplasia Am J Med Genet 124A:202–208, 2004 Oculo-ectodermal syndrome – macrocephaly, cutis aplasia, abnormal pigmentation, scalp nodules, corneal epibulbar dermoid cysts BJD 151:953–960, 2004 Odonto-onycho-dermal dysplasia – oligodontia with small widely spaced conical peg-shaped teeth, hypodontia, absence of secondary teeth; palmoplantar keratoderma, hyperhidrosis, dystrophic nails, erythematous telangiectatic, reticulated atrophic malar and ala nasal patches with vermiculate scarring JAAD 57:732–733, 2007; Am J Med Genet 14:335–346, 1983 Opitz syndrome – membranous aplasia cutis with hypertelorism, cleft lip/palate, hypospadias, cryptorchidism Osteodysplastic geroderma (Walt Disney dwarfism) – short stature, cutis laxa-like changes with drooping eyelids and jowls, osteoporosis and skeletal abnormalities Am J Med Genet 3:389–395, 1979 Osteogenesis imperfecta - blue sclerae; thin fragile skin J Med Genet 16:101–116, 1979 Panhypopituitary dwarfism – short stature, excess subcutaneous fat, high pitched voice, soft, wrinkled skin, child-like facies Birth Defects 12:15–29, 1976 Parry-Romberg syndrome Ped Derm 36:223–226, 2019; JAAD 67:769–784, 2012; JAAD 56:257–263, 2007; Ped Derm 21:48–50, 2004; Hautarzt 47:599–603, 1996; JAAD 22:531–533, 1990; Klinische Ergebnisse. Berlin. Forstner; 1846. pp.75–81 Partial lipodystrophy, complement abnormalities, vasculitis – macroglossia, polyarthralgia, mononeuritis, hypertrophy of subcutaneous tissue Ann DV 114:1083–1091, 1987 Patau syndrome (Trisomy 13) – capillary hemangiomas of the forehead, localized scalp defects G Ital DV 121:25–28, 1986 Patterson David syndrome - pseudoleprechaunism Penttinen syndrome – progeroid disorder with overgrowth; resembles mandibuloacral dysplasia (which has micrognathia); hypertelorism, malar hypoplasia, prognathia, narrow nose; open font, shallow orbits, lipoatrophy with thin translucent skin; scars overlying joints; acroosteolysis Am J Med Genet A 161A:1786–1791, 2013; Am J Med Genet 69:182–187, 1997 Perilipin deficiency and autosomal dominant partial lipodystrophy – partial lipodystrophy, severe dyslipidemia, insulin-resistant diabetes; paucity of subcutaneous fat and muscular appearance mutation in PLIN1 NEJM 364:740–748, 2011 Phakomatosis pigmentokeratotica – hemiatrophy; hemihypertrophy; coexistence of an organoid nevus and a checkerboard papular speckled lentiginous nevus; organoid nevus associated with hypophosphatemic vitamin D-resistant rickets Ped Derm 25:76–80, 2008; JAAD 55:S16–20, 2006 PHACES syndrome – sternal depression BJD 155:192–194, 2006 POEMS syndrome – facial lipoatrophy, hemangiomas, diffuse hyperpigmentation, skin thickening (pseudosclerosis), acrocyanosis, hypertrichosis of head and legs, white nails, livedo racemosa, Raynaud’s phenomenon AD 146:615–623, 2010 Poikiloderma with neutropenia – autosomal recessive; Navajo Indians; erythematous rash of limbs, trunk, and face beginning in infancy; evolves into poikiloderma; recurrent infections; palmoplantar keratoderma; pachyonychia of great toenails, photosensitivity; growth retardation; dental caries; atrophic scars; mutation in C16orf57 BJD 163:866–869, 2010; Am J Med Genet A 146A:2762– 2769, 2008; Am J Hum Genet 86:72–76, 1991

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Poland syndrome – unilateral chest wall and upper extremity hypoplasia due to subclavian artery hypoplasia; oligodactyly NEJM 378:72, 2017; JAMA Derm 150:1019–1020, 2014

144:1215–1218, 2001; JAAD 39:853–857, 1998; Acta DV 61:497– 503, 1981

PPAR gamma familial partial lipodystrophy – facial and forearm and calf lipoatrophy NEJM 350:1220–1234, 2004

Ruvalcaba syndrome - atrophic plaques on trunk

Premature aging and short stature syndrome (Mulvihill-Smith syndrome) - loss of facial subcutaneous tissue Proteus syndrome – lipohypoplasia and patchy dermal hypoplasia AD 140:947–953, 2004; AD 133:77–80, 1997 Prune belly syndrome (aplastic abdominal musculature syndrome) (Triad syndrome; Eagle-Barrett syndrome, urethral obstruction malformation sequence) – abdominal muscle hypoplasia, urinary tract abnormalities, bilateral cryptorchidism, pulmonary, skeletal, cardiac and gastrointestinal abnormalities; cerebriform appearance of abdomen; loose and wrinkled skin at birth JAAD 72:1066–1073, 2015; Ped Derm 23:342–345, 2006; J Urol 139:335–337, 1988

Rothmund-Thomson syndrome (poikiloderma congenitale) Sakati syndrome – patchy alopecia with atrophic skin above ears, submental linear scars, acrocephalopolysyndactyly, short limbs, congenital heart disease, abnormally shaped low-set ears, ear tag, short neck with low hairline J Pediatr 79:104–109, 1971 SAM syndrome (severe dermatitis, multiple allergies, metabolic wasting) – biallelic loss of function mutations in desmoglein1 (Dsg1); palmoplantar keratoderma, psoriasiform plaques, multiple allergies BJD 172:257–261, 2015 Say-Barber syndrome – short stature, microcephaly, large ears, flexion contractures, decreased subcutaneous fat; dermatitis in infancy with transient hypogammaglobulinemia Am J Med Genet 86:165–167, 1999

Pseudoxanthoma elasticum penicillamine-induced pseudoxanthoma elasticum JAAD 30:103–107, 1994; Dermatology 184:12–18, 1992; saltpetre-induced pseudoxanthoma elasticum Acta DV 58:323–327, 1978

SCALP syndrome – sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis JAAD 58:884–888, 2008

PYCR1-related cutis laxa – hair loss, prominent scalp veins, triangular shaped face, microcephaly, short stature, hypermobility of joints, thin atrophic skin, wrinkled skin, muscle weakness, finger contractures Dtsch Arztebl Intl 16:489–496, 2019

Scleroatrophic and keratotic dermatosis of limbs (scleroatrophic syndrome of Huriez) - autosomal dominant; scleroatrophy of hands, sclerodactyly, palmoplantar keratoderma, xerosis, hypoplastic nails BJD 143:1091–1096, 2000; BJD 134:512–518, 1996; Bull Soc Fr Dermatol Syphiligr 70:24–28, 1963

Rapp-Hodgkin ectodermal dysplasia Reflex sympathetic dystrophy – glossy edematous, sclerodermatous skin, taut fingers, alopecia JAAD 58:320–322, 2008; Cutis 68:179– 182, 2001; AD 127:1541–1544, 1991; JAAD 22:513–520, 1990 Restrictive dermopathy (stiff skin syndrome) – autosomal recessive; rigid translucent inelastic skin; prominent vessels, skin erosion, dysmorphism including hypertelorism, antimongoloid axis, sparse eyelashes and eyebrows, pinched nose, O-shaped mouth, natal teeth, microretrognathia, multiple joint contractures, dysplastic clavicles, thin ribs; rocker-bottom feet; severe intrauterine growth retardation; micrognathia, fixed facial expression, low set ears; pulmonary hypoplasia; zinc metalloproteinase (ZMPSTE24 or dominant lamin A/C gene mutations), Ped Derm 28:408–411, 2011; AD 138:831–836, 2002 Reticulolinear aplasia cutis congenita of the face and neck – Xp deletion syndrome, MIDAS (microphthalmia, dermal aplasia, sclerocornea), MLS (microphthalmia and linear skin defects), and Gazali-Temple syndrome; lethal in males; residual facial scarring in females, short stature, organ malformations BJD 138:1046–1052, 1998 Robert’s pseudothalidomide syndrome (hypomelia-hypotrichosisfacial hemangioma syndrome) (Roberts/SC phocomelia syndrome) – autosomal recessive; mid-facial port wine stain extending from forehead to nose and philtrum, cleft lip +/- cleft palate, sparse silver-blond hair, limb reduction malformation, characteristic facies, malformed ears with hypoplastic lobules, micrognathia; hypoplastic nares, marked growth retardation JAAD 56:541–564, 2007; Curr Probl Dermatol 3:69–107, 1995; Clin Genet 31:170–177, 1987; Clin Genet 5:1–16, 1974 Romberg syndrome (facial hemiatrophy) Arch Neurol 39:44–46, 1982 Rombo syndrome – autosomal dominant; acral erythema, cyanotic redness of hands and lips, follicular atrophy (atrophoderma vermiculata), milia-like papules and cysts of the face and trunk, telangiectasias, red face, red ears with telangiectasia, thin eyebrows, sparse beard hair, basal cell carcinomas, trichoepitheliomas, short stature with short trunk Ped Derm 23:149–151, 2006; BJD

Segmental neurofibromatosis – blue-red pseudoatrophic plaques Cutis 94:149–152, 2014 Setleis syndrome (focal facial dermal dysplasia type III) – aged leonine appearance, bi-temporal scar-like defects, absent or multiple rows of upper eyelashes, eyebrows slanted up and out, scar-like median furrow of chin Ped Derm 24:555–556, 2007; BJD 130:645–649, 1994; Pediatrics 32:540–548, 1963 SHORT syndrome Syndromes of the Head and Neck, p. 826, 1990 Sjogren’s syndrome – atrophic vulvitis, anal mucosa Sweet’s syndrome – in infancy with acquired cutis laxa Ped Derm 26:358–360, 2009 Terminal osseous dysplasia and pigmentary defects – regional skin hypoplasia; X-linked dominant; digital fibromas, punched out pigmentary anomalies of face and scalp, eye anomalies (colobomas, hypertelorism) Ped Derm 24:280–284, 2007; Am J Med Genet 124A:202–208, 2004 Thoracic outlet syndrome Treacher-Collins syndrome Tricho-odonto onycho-ectodermal dysplasia (linear dermal hypoplasia) - hypotrichosis, hypodontia, focal linear dermal hypoplasia of the tip of the nose, irregular hyperpigmentation of the back, bilateral amastia and athelia, nerve hearing loss AD 122: 1047–1053, 1986 Trichothiodystrophy syndromes - BIDS, IBIDS, PIBIDS – facial hemiatrophy, lipoatrophy, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation Ped Derm 14:441–445, 1997; JAAD 44:891– 920, 2001 Trisomy D (13–15) – membranous aplasia cutis, holoprosencephaly, seizures, ocular abnormalities, deafness, neural tube defects Trisomy 13/18 – scalp defects BJD 151:953–960, 2004; thin or atrophic nails

Atrophic Lesions Tuberous sclerosis - hypoplasia of the hand BJD 135:1–5, 1996; dental pits JAAD 57:189–202, 2007 Turner’s syndrome - thinning and wrinkling of palmar skin; thin or atrophic nails Unusual facies, lipodystrophy, joint contractures (Werner-like disorder) Hum Genet 83:209–216, 1989

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Semicircular lipoatrophy – pressure from leg crossing; anterolateral thigh, lateral calf NEJM 350:1220–1234, 2004

VASCULAR Acrocyanosis with atrophy AD 124:263–268, 1988

Van der Woude syndrome – congenital lower lip pits

Arteriovenous malformation - personal observation

Vertebral and eye anomalies, cutis aplasia, and short stature (VECS) Am J Med Genet 77:225–227, 1998

Atrophie blanche (livedo with ulceration) – ivory white plaque of sclerosis with stippled telangiectasias and surrounding hyperpigmentation; venous insufficiency, thalassemia minor Acta DV (Stockh)50:125–128, 1970; cryoglobulinemia, systemic lupus erythematosus, scleroderma Arch Pathol Lab Med 110:517–519, 1986; JAAD 8:792–798, 1983; AD 119:963–969, 1983

Werner’s syndrome – loss of subcutaneous tissue; bird-like facies, spindly legs Am J Med 108:143–152, 2000; AD 124:90–101, 1988 Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – generalized lipoatrophy, macrocephaly, premature aging, wide open sutures, hypoplasia of facial bones, low set ears, beak shaped nose, neonatal teeth, slender limbs, large hands and feet with long fingers, large penis J Med Genet 34:433–437, 1997 Williams syndrome – premature laxity of skin, congenital heart disease (supravalvular aortic stenosis), baggy eyes, full cheeks, prominent lips, dental malocclusion, delayed motor skills, cocktail party personality J Pediatr 113:318–326, 1988 Wolf-Hirschhorn syndrome (del (4p) syndrome) – midline scalp defect BJD 151:953–960, 2004; Am J Med Genet 21:351–358, 1985 Wrinkly skin syndrome(possibly same as geroderma osteodysplastica) – autosomal recessive; aged appearance with wrinkled skin on abdomen and dorsal aspects of hands and feet, increase palmoplantar creases, prominent venous pattern on chest, intrauterine growth retardation, mental retardation, microcephaly, hypotonia, musculoskeletal abnormalities Ped Derm 25:66–71, 2008; Ped Derm 23:467–472, 2006; Am J Med Genet 101:213–220, 2001; Ped Derm 16:113–117, 1999 X-linked ectodermal dysplasia with immunodeficiency – NEMO mutation; erythroderma, alopecia, red scaly scalp, frontal bossing, periorbital wrinkling, intertrigo, thick everted lower lip AD 144:342– 346, 2008 X-p22 microdeletion syndrome – bilateral reticulated and linear defects of malar region of face, microphthalmia, sclerocornea Xeroderma pigmentosum

Capillary malformation in segmental distribution – central atrophy; serpiginous; geographic JAAD 83:213–214, 2020 Cerebral large venous malformations (cavernomas) associated with en coup de sabre (hyperpigmentation and atrophy) Ped Derm 37:237–238, 2020 Congenital plaque type glomuvenous malformations – glomulin gene on 1p21; loss of function mutation; atrophic at birth; livedoid plaques, blue plaques, vascular nodules, red patches, cerebriform, targetoid; atrophic patch with redundant skin Soc Ped Derm Annual Meeting, July 2005; AD 142:892–896, 2006 Cutis marmorata telangiectatica congenita – facial or limb hypoplasia with livedo reticularis BJD 170:681–686, 2014; JAAD 56:541–564, 2007; JAAD 48:950–954, 2003; Ped Derm 17:100–104, 2000; JAAD 20:1098–1104, 1989; may be associated with aplasia cutis congenital JAAD 56:541–564, 2007 Degos’ disease (malignant atrophic papulosis) - flat, white papules with erythematous telangiectatic halos NEJM 370:2327–2337, 2014; white atrophic papules AD 145:321–326, 2009; BJD 139:708–712, 1998; AD 128:255–260, 1992; lower extremity hypoplasia Turk J Pediatr 43:159–161, 2001 Edema - acute leg edema; stria-like distension of skin AD 138:641– 642, 2002 Gorham-Stout phenomenon – lymphatic malformations with bone resorption JAAD 65:893–906, 2011 Hemangiomas, resolved – atrophy, telangiectasia, redundant skin

TRAUMA Acupuncture – atrophic round scars BJD 150:364, 2004 Amniocentesis dimples Am J Obstet Gynecol 126:247–252, 1976; JAAD 39:888–890, 1998; AD 120:1360–1362, 1984 Cardioversion (defibrillation) – hypopigmented, atrophic, telangiectatic, crusted erythematous plaque of back with rim of hyperpigmentation; delayed onset of years AD 145:1411–1414, 2009 Compression from tight fitting clothes - lipoatrophy JAAD 45:325– 361, 2001 IVDA - skin popping BJD 150:1–10, 2004 Injection-induced lipoatrophy – corticosteroid and insulin NEJM 350:1220–1234, 2004 Injury due to obstetric forceps or scalp electrodes Localized involutional lipoatrophy – secondary to injection, suction, massage JAAD 58:490–493, 2008 Radiation dermatitis, chronic JAAD 54:28–46, 2006 Reflex sympathetic dystrophy (complex regional pain syndrome) – erythema and edema; muscle wasting JAMA Derm 150:640–642, 2014 Scars

Klippel-Trenaunay syndrome (port wine stain, varicosities) – limb atrophy (hypoplasia); ectrodactyly (absence of digits) JAAD 61:621–628, 2009; J Pediatr Orthop 12:401–402, 1992 Livedoid vasculopathy (atrophie blanche en plaque; atrophie blanche with summer ulceration) – painful purpuric papules and plaques; leg and ankle ulcers; atrophic white scars; livedo reticularis JAAD 69:1033–1042, 2013 Lymphangioma – erythematous depressed patch of upper back as sign of underlying systemic lymphangiomatosis; history of chylothorax BJD 163:875–877, 2010 PHACES syndrome – midline sternal notch; cervicofacial hemangioma; structural arterial brain malformations Eur J Pediatr Jan, 2007; JAAD 55:1072–1074, 2006; Clin Pediatr 44:747, 2005 Rapidly involuting congenital hemangioma (RICH) – residual patch of thin skin with prominent veins after involution JAAD 50: 875–882, 2004; of face with cutis laxa-like appearance; post-involutional subcutaneous atrophy Soc Ped Derm Annual Meeting, July, 2006 Reticular infantile hemangioma with minimal or arrested growth associated with lipoatrophy JAAD 72:828–833, 2015 Servelle-Martorell syndrome – association of capillary stains and dysplastic veins with undergrowth of affected limb JAAD 65:893–

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

906, 2011; JAAD 56:541–564, 2007; Curr Prob in Dermatol 13:249–300, 2002 Varicose veins – acquired localized elastolysis Clin Exp Dermatol 20:492–495, 1995 Venous malformations (genuine diffuse phlebectasia) (Bockenheimer syndrome) – musculoskeletal hypotrophy with synovial siderosis; degenerative arthritis with amyotrophy of leg, flexions contractures; ankylosis of the knee JAAD 65:893–906, 2011

SYNDROMES WITH THINNESS OR EMACIATION AIDS Cockayne syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.166–167 Congenital generalized lipodystrophy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.280–281 Diencephalic tumor-emaciation syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.284–285 Hutchinson-Gilford syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.270–271 Rigid spine syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp446–447 SHORT syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.549–550 Xeroderma pigmentosum – atrophic skin, atrophic lips JAAD 75:855–870, 2016 Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – generalized lipoatrophy, macrocephaly, premature aging, wide open sutures, hypoplasia of facial bones, low set ears, beak shaped nose, neonatal teeth, slender limbs, large hands and feet with long fingers, large penis J Med Genet 34:433–437, 1997

AUTOINFLAMMATORY DISEASES Ped Derm 33:602–614, 2016 A20 haploinsufficiency (HA 20) – loss of function mutation in TNF AIP3 - mimics pediatric Behcet’s disease Ped Derm 33:602–614, 2016 Autoinflammatory syndrome with lymphedema (AISLE) – fever and urticarial, progressive edema of scrotum and legs; mutation in MyoD family inhibitor domain-containing protein Ped Derm 33:602–614, 2016 Behcet’s disease CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis, epidydimitis, coldinduced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, conjunctivitis Ped Derm 33:602–614, 2016 C1q deficiency – atrophic fingers and toes, hypopigmentation, finger tapering, butterfly rash, discoid lupus lesions, Raynaud’s phenomenon; renal disease – segmental mesangiopathic glomerulonephritis; increased interferon 1 levels Ped Derm 33:602–614, 2016

Cryopyrin-associated periodic syndromes (CAPS) – urticarial-like eruptions, fever, distal arthralgia, neurologic symptoms, eye disease, amyloidosis; NLRP3 gene Ped Derm 33:602–614, 2016; JAAD 68:834–853, 2013   Familial cold autoinflammatory syndrome   Muckle-Wells syndrome   Neonatal-onset multisystem inflammatory disease (NOMID) Familial Mediterranean fever; autosomal recessive; erysipelas-like erythema of lower leg, ankle, or foot; MEFV gene Ped Derm 33:602–614, 2016 H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; mutation in SLC29A3 gene (equilabrative nucleoside transporter) Ped Derm 33:602–614, 2016 Juvenile systemic granulomatosis (Blau syndrome, early onset sarcoid) – granulomatous dermatitis, arthritis, uveitis; NOD2 gene Ped Derm 33:602–614, 2016 Mevalonate kinase deficiency Ped Derm 33:602–614, 2016   Hyper IgD with periodic fever syndrome (HID syndrome)   Mevalonic aciduria   Morbilliform eruption of palms and soles Inflammatory bone diseases Ped Derm 33:602–614, 2016   Deficiency of IL-1 receptor antagonist (DIRA)   Chronic multifocal osteomyelitis   Cutaneous pustules, joint swelling, periostitis, fever  Majeed syndrome – autosomal recessive; chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, inflammatory dermatosis Macrophage activation diseases Ped Derm 33:602–614, 2016   Systemic onset juvenile idiopathic arthritis  Adult-onset Still’s disease – evanescent salmon colored eruption, atypical persistent papules and plaques Clin Derm 37:668–674, 2019   Primary familial hemophagocytic lymphohistiocytosis NLRP 1-associated autoinflammatory arthritis and dyskeratosis – phrynoderma; increased caspase 1 function; increased IL-18 Ped Derm 33:602–614, 2016 Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) Ped Derm 33:602–614, 2016 Periodic fever, immunodeficiency, and thrombocytopenia – severe oral ulcers leading to scarring and microstomy; fever, poor growth, infections, thrombocytopenia Ped Derm 33:602–614, 2016 Pyogenic diseases Ped Derm 33:602–614, 2016  Deficiency of IL-36R antagonist (DITRA) – generalized pustular eruption, neutrophilia, fever, nail dystrophies, glossitis, oligoarthritis   Familial psoriasis (PSORS2)  Pyogenic sterile arthritis, pyoderma gangrenosum, acne vulgaris (PAPA) – autosomal dominant; mutation in PSTPIP1  PASH – pyoderma gangrenosum, acne, suppurative hidradenitis); mutation in nicastrin, a gamma-secretase gene and PSTPIP1 Clin Exp Dermatol 44:918–920, 2019 PLCG2-associated diseases Ped Derm 33:602–614, 2016  PLCG2- associated antibody deficiency and immune dysregulation (APLAID)  Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation

Autoinflammatory Diseases Pyrin-associated autoinflammatory neutrophilic disease (PAAND) – autosomal dominant; facial pustules, pyoderma gangrenosum lesions; mutation in MEFV Ped Derm 33:602–614, 2016 SAVI – STING-associated vasculopathy with onset in infancy syndrome – autosomal dominant; gain of function mutation in transmembrane protein 173 (STING) leading to chronic activation of Type I interferon pathway; violaceous scaling plaques of fingers, toes, nose, ears, cheeks; red ears which ulcerate with necrosis; nail loss, nail dystrophy, nasal septal perforation, severe interstitial lung disease Ped Derm 33:602–614, 2016 Schnitzler’s syndrome – IgM kappa paraprotein (rarely IgG) and recurrent urticarial, fever, leukocytosis, abnormal bone remodeling +/- pain Ped Derm 33:602–614, 2016 Tumor necrosis factor receptor associated periodic fever (TRAPS) – autosomal dominant; erythematous migratory rash on torso or extremity; mutation in TNFRSF1A gene Ped Derm 33:602–614, 2016 X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with unswept hair, flared eyebrows; female carriers display blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

 ISORDERS OF MANAGEMENT OF NUCLEIC ACID D CONTENTS H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; mutation in SLC29A3 gene (equilabrative nucleoside transporter) Ped Derm 33:602–614, 2016 Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – autosomal recessive; mutation in cat eye syndrome chromosome candidate 1

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gene; livedo reticularis, Raynaud’s phenomenon, necrosis, fever, early recurrent strokes, hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 33:602–614, 2016

TYPE I INTERFERONOPATHIES  Aicardi-Goutieres syndrome – autosomal recessive; neurodegenerative disease; mutation in three-prime repair exonuclease 1 (TREX1;AGS1); mutation in sterile alpha motif domain and HD domain-containing protein1 (SAMHD1;AGS5); mutation in 3 genes encoding for components of ribonuclease H@ subunit A endonuclease complex (AGS2–4); mutation in gene for RNAspecific adenosine deaminase 1 (AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1 (AGS7); chilblain-like lesions; acrocyanosis; red periungual lesions; red earlobes; livedo reticularis, blueberry muffin baby; congenital encephalopathy with developmental delay; microcephaly; narrow facial features; seizures, spasticity, dystonic posturing Ped Derm 33:602–614, 2016  C1q deficiency – atrophic fingers and toes, hypopigmentation, finger tapering, butterfly rash, discoid lupus lesions, Raynaud’s phenomenon; renal disease – segmental mesangiopathic glomerulonephritis; increased interferon 1 levels Ped Derm 33:602–614, 2016  SAVI – STING-associated vasculopathy with onset in infancy syndrome – autosomal dominant; gain of function mutation in transmembrane protein 173 (STING) leading to chronic activation of Type I interferon pathway; violaceous scaling plaques of fingers, toes, nose, ears, cheeks; red ears which ulcerate with necrosis; nail loss, nail dystrophy, nasal septal perforation, severe interstitial lung disease Ped Derm 33:602–614, 2016  Familial chilblain lupus – autosomal dominant; violaceous erythema and scaling of toes; ulcers, arthralgias and arthritis; mutation in SAMHD1 and TREX 1 Ped Derm 33:602–614, 2016  X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with unswept hair, flared eyebrows; female carriers display blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

 ARIATRIC SURGERY, CUTANEOUS B SIGNS OF NUTRIENT DEFICIENCY NEJM 368:e29, 2013; CMAJ 185, 2013; Clin Dermatol 28:669–685, 2010; NEJM 356:2176–2183, 2007; An Bras Dermatol 90:157–168, 2015; Pediatr Clin N Amer 45:245–260, 1998

TYPES OF BARIATRIC SURGERY 1. Restrictive – no major nutrient deficiency; folate deficiency possible Vertical banded gastroplasty Laparoscopic adjustable gastric banding Sleeve gastrectomy 2. Malabsorptive – macronutrient (protein, carbohydrate, fat) and micronutrient (vitamins and minerals) deficiency Biliopancreatic diversion Biliopancreatic diversion with duodenal switch 3. Mixed restrictive and malabsorptive – micronutrient deficiency (vitamins and minerals)

METABOLIC AND NUTRITIONAL DISORDERS Biotin – from egg yolks, liver, nuts, peanuts, mushrooms, cow’s milk, soy  Alopecia  Glossitis   Keratosis pilaris   Periorificial dermatitis   Seborrheic dermatitis  Erythroderma  Conjunctivitis Copper – meat, seafood, vegetables, grains, nuts   Hypopigmentation of the hair; premature gray hair   Brittle hair  Pallor   Delayed wound healing   Pancytopenia, unsteady gait, and distal paresthesias Iron – red meat, eggs, dairy  Pallor  Glossitis  Koilonychia  Pruritus Selenium – rice, beans, flour  Alopecia  Hypopigmentation   Impaired wound healing  Leukonychia   Psoriasis (increased risk)   Skin cancer risk  Xerosis   Muscle pain and weakness Vitamin A (retinol) – protein is necessary for vitamin A assimilation; animal products (milk, liver, eggs); green and brightly colored vegetables   Bitot’s spots – xerophthalmia leading to blindness  Phrynoderma – follicular keratotic papules of anterolateral thighs and arms  Xeroderma   Brittle hair   Dry mouth

Vitamin B2 (riboflavin) – absorbed in proximal small intestine; dairy products, fish, eggs, leafy greens, whole grains  Mucositis   Angular cheilitis  Cheilitis  Glossitis  Xerosis   Seborrheic dermatitis   Scrotal/vulvar dermatitis  Erythroderma   Toxic epidermal necrolysis Vitamin B3 (niacin) – meat, poultry, nuts, eggs, fish, coffee, beans  Pellagra – diarrhea, dermatitis (symmetrical sun-exposed areas, Casal’s necklace) – sharply demarcated symmetrical hyperpigmentation of the hands and feet; glove, gauntlet, or boot distribution; small yellow flakes from dilated orifices of the nose, face; rough powdery appearance, dementia  Cheilitis  Glossitis   Skin thickening and pigmentation over bony prominences   Black tongue Vitamin B5 (pantothenic acid) – egg yolk, liver, kidney, broccoli, chicken, beef, milk, potatoes, whole grains  Purpura   Leukotrichia (white hair)   Seborrheic dermatitis   Angular stomatitis  Glossitis   Burning feet syndrome Vitamin B6 – absorbed in jejunum and ileum; meat, whole grains, nuts   Seborrheic dermatitis  Glossitis   Oral ulcers   Lip and angular cheilitis Vitamin B9 (folic acid) – liver, grains, leafy green vegetables, dried beans   Angular cheilitis   Hunter’s glossitis – atrophy of filiform papillae, erythema, pain  Diffuse, symmetric hair and mucocutaneous hypo- and hyperpigmentation   Hyperpigmentation of the palms and soles   Canities (premature graying of the hair) Vitamin B12 (cobalamin) – liver, eggs, milk, beef, organ meats   Angular cheilitis   Hunter’s glossitis – atrophy of filiform papillae, erythema, pain  Diffuse, symmetric hair and mucocutaneous hypo- and hyperpigmentation   Hyperpigmentation of the palms and soles   Canities (premature graying of the hair) Vitamin C (ascorbic acid) – absorbed in upper 1/3 of intestine; citrus fruits, strawberries, tomatoes, vegetables, potatoes  Scurvy – keratosis pilaris, hemorrhage, bleeding gums, conjunctivae, and gastrointestinal tract, xerosis, keratoconjunctivitis, linear nail hemorrhages, corkscrew hair; nonthrombocytopenic non-palpable purpura; follicular hyperkeratosis with perifollicular hemorrhage   Poor wound healing  Subperiosteal hemorrhage with hip and knee pain; “pseudoparalysis”   “Scorbutic rosary” – swelling of costochondral joints Vitamin D – fish oils, egg, liver, shiitake mushrooms, fortified milk and orange juice   Atopic dermatitis

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Basal Cell Carcinomas: Syndromes with Basal Cell Carcinomas  Psoriasis   Skin infections   Acne vulgaris   Autoimmune cutaneous diseases   Skin cancer Vitamin E – vegetable oils   Atopic dermatitis   Acne vulgaris Vitamin K – leafy greens, liver, lentil, soy, vegetable oils  Purpura (petechiae, ecchymosis, hematoma) Zinc – animal products, legumes, whole grains, dairy  Acrodermatitis enteropathica – diarrhea, alopecia, acral and periorificial rash NEJM 371:67, 2014   Dry, brittle hair   Vitiligo-like lesions   Delayed wound healing  Paronychia   Stomatitis, angular cheilitis, blepharitis   Psoriasiform dermatitis Protein – meat, poultry, beans, eggs, soy, nuts   Kwashiorkor (protein) and marasmus (protein and calorie)  Dry, wrinkled skin; “flaky paint,” “crazy paving,” “enamel paint dermatitis” –well-demarcated, hyperpigmented plaques, thick scales, fissures, and erosions   Erythematous, hypochromic flexures  Onychomadesis   Follicular hyperkeratosis   Dry, brittle, thin hair  Flag sign – reddish-brown hair with intermittent grayish-white hair   Angular cheilitis  Xerophthalmia  Stomatitis  Vulvovaginitis

BARIATRIC SURGERY-SPECIFIC SKIN CHANGES Psoriasis remission Necrobiosis lipoidica diabeticorum resolution Post-bariatric surgery skin excess

 ASAL CELL CARCINOMAS: B SYNDROMES WITH BASAL CELL CARCINOMAS Bazex-Dupre-Christol syndrome (X-linked dominant) – milia and comedo-like papules, congenital hypotrichosis, anhidrosis of the face and head, facial hyperpigmentation, follicular (vermiculate) atrophoderma of the face, elbows, and dorsal hands; basal cell carcinomas resemble nevi; multiple follicular hamartomas with sweat gland and sebaceous differentiation; trichoepitheliomas JAAD 74:437–451, 2016; Ped Derm 28:727–728, 2011; BJD 165:30–34, 2011; Ped Derm 25:112– 113, 2008; Derm Surg 26:152–154, 2000; Ped Derm 16:108– 110, 1999; JAAD 39:853–857, 1998; J Med Genet 33:493–497, 1996; AD 130:337–342, 1994; Clin Exp Dermatol 6:31–41, 1981; Ann Dermatol Syphilgr (Paris) 93:241–254, 1966

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Coarse sparse hair and milia syndrome JAAD 50:489–494, 2004 Happle-Tinschert syndrome – basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, palmoplantar pitting, atrophoderma, hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia, coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020 Multiple hereditary nonsyndromic basal cell carcinomas JAAD 50:489–494, 2004 Nevoid basal cell carcinoma syndrome(Gorlin’s syndrome) – autosomal dominant; basal cell carcinomas, basaloid follicular hamartomas, linear hypo- or hyperpigmented lesions; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microphthalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors (fibromas), mesenteric cysts, cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism, BJD 182:212–217, 2020; BJD 165:30–34, 2011; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908–912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004 Nevus sebaceus syndrome Oculocutaneous albinism Oley syndrome – coarse sparse hair, milia, basal cell carcinomas BJD 165:30–34, 2011; Am J Med Genet 43:799–804, 1992 Rombo syndrome – autosomal dominant; acral erythema, cyanotic redness of the hands and lips, follicular atrophy (atrophoderma vermiculata) of sun-exposed skin (cheeks and elbows), milia-like papules and cysts of the face and trunk, telangiectasias, red face with perioral cyanotic erythema, red ears with telangiectasia, thin eyebrows, sparse beard hair, basal cell carcinomas, trichoepitheliomas, short stature with short trunk JAAD 74:437–451, 2016; BJD 165:30–34, 2011; Ped Derm 23:149–151, 2006; BJD 144:1215– 1218, 2001; JAAD 39:853–857, 1998; Acta DV 61:497–503, 1981 Xeroderma pigmentosum JAAD 50:489–494, 2004; New Sydenham Soc 61:252–258, 1874

BIOWEAPONS CATEGORY A JAAD 65:1213–1218, 2011 Anthrax Botulism Plague Smallpox Tularemia Viral hemorrhagic fevers

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

“BLACK” DERMATOLOGIC ENTITIES

Imipramine – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Lansoprazole (proton pump inhibitor) – black tongue AD 137:968– 969, 2001; BJD 144:1293–1294, 2001

Allergic contact dermatitis – “black” poison ivy due to oxidation of resin Ped Derm 27:395–396, 2010; Dermatitis 19:48–51, 2008; JAAD 45:246–249, 2001; JAAD 6:363–368, 1982; black lacquer dermatitis Autoimmune blistering disorders – blisters with central black dots Dermatitis herpetiformis – black palmar lesions in purpuric dermatitis herpetiformis Ped Derm 14:319–322, 1994

Levofloxacin – blue-black macules of the hands and legs AD 143:1441–1446, 2007 Methyldopa – black tongue AD 137:968–969, 2001; AD 136:427– 428, 2000 Minocycline – black galactorrhea AD 121:417–418, 1985; black tongue AD 137:968–969, 2001; BJD 134:943–944, 1996; AD 131:620, 1995; AD 121:417–418, 1985; black nails

Dermatomyositis – epidermal necrosis Cutis 61:190–194, 1998

Nortryptiline – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

Graft vs. host disease – linear epidermal necrosis with black line JAAD 1/94

Penicillins – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

Lupus erythematosus – lupus profundus; LE hypertrophicus et profundus – verrucous brown-black plaque BJD 96:75–78, 1977

Phenothiazine – black galactorrhea AD 121:417–418, 1985

CONGENITAL LESIONS Dermoid cyst – personal observation

DRUG-INDUCED Amitriptyline – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

Psychotropic drugs, including chlorpromazine, thioridazine, imipramine, desipramine hydrochloride, amitriptyline hydrochloride – gray to blue-black hyperpigmentation JAMADerm 150:984–989, 2014 Sparfloxacin – blue-black pigmentation Clin in Derm 37:468–486, 2019 Streptomycin – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Sulfonamides – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

Argyria – blue-black pigmentation Clin in Derm 37:468–486, 2019

Telaprevir – perforating disorder – black hyperkeratotic nodules JAMADerm 150:1371–1372, 2014

Benztropine – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

Tetracycline – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003

Bismuth subsalicylate – black dots after oral ingestion of PeptoBismol JAAD 37:489–490, 1997

Vasopressive agents – peripheral ischemia with black toes NEJM 369:1047–1054, 2013

Black hairy tongue – multiple antibiotics Calcium gluconate, extravasated – linear and dot-like black necrosis Cephalosporins – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Clarithromycin – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Clofazimine – red to purple black Clonazepam – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Corticosteroids – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Diltiazem – blue-black, photodistributed hyperpigmentation JAAD 46:468–469, 2002 Etanercept – 1 mm angiokeratomas at injection sites JAAD 59:S124–125, 2008 Fluoxetine – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Gefitinib – blue-black pigmentation Clin in Derm 37:468–486, 2019 Gold salts – black nails Griseofulvin – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003 Heparin, low molecular weight – intraepidermal bullous hemorrhage BJD 161:191–193, 2009; heparin-induced skin necrosis – black necrotic bullae of the abdomen JAAD 71:1033–1035, 2014 Hydroxychloroquine – blue-black pigmentation

EXOGENOUS AGENTS Acupuncture beads Anthralin staining Bismuth subsalicylate – pseudo-black hairy tongue Cutis 105:288,293, 2020 Black dermatographism – blackening of skin by metals; rubbing of metal with zinc oxide, ferric oxide, pumice, titanium dioxide Cutis 52:17–19, 1993; JAMA 121:485–490, 1943 Black tattoos – carbon (India ink), iron oxide, or logwood – tattoo reaction JAAD 35:477–479, 1996 Cactus – dome-shaped skin-colored papules with central black dot Cocaine abuse – black hyperkeratotic hands (crack hands); freebase cocaine crack pipe; black burns of the fingertips Curr Drug Abuse Rev 5:64–83, 2012; JAAD 59:483–487, 2008; Chest 121:289–291, 2002; Cutis 50:193–194, 1992 Clothing dyes – released by sweating Crack cocaine – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003; AD 137:968–969, 2001 Foreign body, including foreign body granuloma; delayed reaction to graphite pencil Cutis 42:199–201, 1988; blackthorn granuloma; sea urchin spines of the soles Inhaled heroin smoke – black tongue (not hairy) AD 143:813, 2007 Ink stain

“Black” Dermatologic Entities Phenol – blue-black pigmentation Clin in Derm 37:468–486, 2019 Sea urchin spicules Skin graft – pseudomelanoma Tobacco – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003; AD 137:968–969, 2001 Vegetable dyes – black tongue (not hairy) AD 143:813, 2007; J Contemp Dent Pract 4:10–31, 2003; AD 137:968–969, 2001

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Mucormycosis – rhino-orbital-cerebral mucormycosis – black necrotic plaque of medial eyelids Cutis 94:168, 195–196, 2014 Mycetoma – black grains; Madurella mycetomatis – brown or black grains JAAD 53:931–951, 2005 Myiasis due to Cordylobia anthropophaga JAAD 126:199–202, 1990 Necrotizing fasciitis – periorbital blue-black necrosis AD 140:664– 666, 2004 Onychomycosis – black nail

INFECTIONS AND INFESTATIONS African tick-bite fever (Rickettsia africae) J Emerg Med 53:904–906, 2017

Osteomyelitis – subungual black macules associated with osteomyelitis of distal phalanges AD 124:418–423, 1988 Pinta – black nails

Anthrax – eschar

Pitted keratolysis

Aspergillosis – primary cutaneous – blisters with central black dots JAAD 31:344–347, 1994; black eschar AD 141:633–638, 2005; Aspergillus fumigatus – necrotic purpura with ulcers; verrucous crusted black giant plaque of the back Ped Derm 27:403–404, 2010

Pseudochromhidrosis – colorless sweat becomes pigmented due to chromogenic bacteria (Corynebacteria)

Bacillus cereus – cutaneous infection begins with vesicle and/or pustule and becomes cellulitis; then a nonhealing ulcer with a black eschar Cutis 79:371–377, 2007; Lancet Mar 18;1(8638):601–603, 1989 Bedbugs (Cimex lectularius) Ped Derm 22:183–187, 2005 Black blowfly (maggot, genus Phormia) Black death (plague, Yersinia pestis) and kala-azar Black dot ringworm Blackflies Black piedra – Piedraia hortae favus(S) JAAD 53:931–951, 2006 Black widow spider bite Condyloma acuminata Coniosporium epidermidis – black macules of the dorsal toes; superficial fungal infection JAAD 63:725–727, 2010 Deer tick – personal observation Diphtheria, cutaneous (Corynebacterium diphtheriae) – black necrotic ulcers of the penis and scrotum Cutis 79:371–377, 2007 Ecthyma – personal observation Emmonsia pasteurina – verrucous and black necrotic nodule JAMADerm 151:1263–1264, 2015 Enterobacter cloacae – black tongue (not hairy) AD 143:813, 2007 Fungal melanonychia (onychomycosis) JAAD 31:311–316, 1994   Acrotherium nigrum   Alternaria grisea tenuis   Alternaria numiocola   Blastomycetes   Candida   Chaetomium kunze   Fusarium oxysporum   Hormodendrum elatum   Phyllosticta sydow   Scytalidium dimidiatum – superficial black onychomycosis AD 140:696–701, 2004   Trichophyton rubrum   Trichophyton soudanense   Wangiella dermatitidis Fusarium and Mucormycosis – black plaques and white nodules JAMADerm 150:1355–1356, 2014 Insect bite reaction – blister with central black dot Lyme disease – blister with central black dot; necrotic bulla Molluscum contagiosum – involuting

Rhizopus oryzae – multiple myeloma; personal observation Rickettsialpox – eschar (tache noire) JAAD 2:359–373, 1980 Scrub typhus (Rickettsia tsutsugamushi) (mites) – headache and conjunctivitis; eschar with black crust; generalized macular or morbilliform rash JAAD 2:359–373, 1980 Streptococcus pyogenes – ecthyma gangrenosum-like lesion (erythematous plaque with central black necrosis) in disseminated streptococcal disease JAMA 311:957–958, 2014 Tick, engorged or non-engorged Br Med J 309:1693, 1994; larval tick infestation (Ixodes dammini) Cutis 82:38–46, 2008 Tick typhus(boutonneuse fever, Kenya tick typhus, African and Indian tick typhus) (ixodid ticks) – small ulcer at the site of tick bite (tache noire) – black necrotic center with red halo; pink morbilliform eruption of forearms, then generalizes, involving face, palms, and soles; may be hemorrhagic; recovery uneventful JAAD 2:359–373, 1980 Tinea capitis – endothrix (T. tonsurans and T. violaceum) – black dots of swollen hair shafts as hairs break at the surface of the scalp JAAD 8:322–330, 1983 Tinea nigra palmaris – Phaeoannellomyces (Exophiala) werneckii Cutis 84:292, 299–300, 2009; JAAD 53:931–951, 2006; Ped Derm 20:315–317, 2003; AD 11:904–905, 1975 Tinea capitis – black dot ringworm Cutis 78:189–196, 2006 Trichomycosis axillaris Tungiasis with central black pit or dot AD 141:389–394, 2005; JAAD 20:941–944, 1989; JAAD 15:117–119, 1986 Zygomycosis – black eschar edema with black discoloration JAAD 75:19–30, 2016; J Pediatr Surg 37:1607–1611, 2002

INFILTRATIVE Dorsal mucoid cysts of the finger AD 129:633–638, 1993 Reactive intravascular histiocytosis – black necrotic eschar of the scrotum and gluteal cleft; associated with tonsillitis; possibly related to reactive angioendotheliomatosis BJD 154:560–563, 2006

INFLAMMATORY DISEASES Erythema multiforme with epidermal necrosis Stevens-Johnson syndrome – personal observation

METABOLIC Aspartylglucosaminuria – angiokeratoma corporis diffusum BJD 147:760–764, 2002

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Calcification – metastatic calcification in chronic renal failure – personal observation

Hemangioma

Calciphylaxis – stellate necrosis and retiform purpura unassociated with renal disease (non-uremic calciphylaxis) – stellate necrosis beginning as mottled purpuric reticulated patches; associated with hyperparathyroidism, malignancy, alcoholic liver disease, connective tissue disease, diabetes mellitus, chemotherapy-induced protein C or S deficiency JAAD 77:241–246, 2017; JAMA 310:1281–1282, 2013

Hidrocystoma – apocrine or eccrine – clear or blue or blue-black; black macules (apocrine) JAAD 54:S53–54, 2006 Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, pp. 153–155; eyelid or facial cyst AD 137:657– 662, 2001; AD 134:1627–1632, 1998; AD 115:194–200, 1979

Hidroacanthoma, pigmented AD 130:913–918, 1994

Diabetes mellitus – finger sticks

Infantile myofibromatosis – purple-black papules and macules AD 136:597–600, 2000; JAAD 41:508, 1999; black plaque with central necrosis JAAD 71:264–270, 2014

Fabry’s disease – angiokeratomas AD 140:1440–1446, 2004

Ink spot lentigo AD 128:934–940, 1992

Hemochromatosis – black hyperpigmented speckling of edematous legs; hyperpigmentation of areolae, flexures, and mucous membranes AD 143:1441–1446, 2007

Kaposi’s sarcoma

Ochronosis – black or blue-black cerumen, urine, cartilage of the nose, sclerae, skin of axillae, around areolae, ends of fingers, cheeks, scleral deposits NEJM 347:2111–2121, 2002; Am J Med 34:813–838, 1963; black nails Peripheral symmetric gangrene, disseminated intravascular coagulation, purpura fulminans; symmetric peripheral gangrene – meningococcemia, staphylococcal sepsis, Capnocytophaga canimorsus JAAD 57:944, 956, 2007; Br Med J 2:8–9, 1891 Vitamin B12 deficiency – black nails

NEOPLASMS Aneurysmal fibrous histiocytomas (variant of dermatofibroma) BJD 153:664–665, 2005 Angiosarcoma – red-black breast nodules following breast irradiation for breast cancer JAAD 54:499–504, 2006; black crusted nodules and plaques Dermatol Online J 25:13030, Dec 15, 2019 Atypical nevus Basal cell carcinoma, pigmented – blue-black papule AD 148:947– 952, 2012; Cutis 71:404–406, 2003 Acta Pathol Microbiol Scand 88A:5–9, 1980; linear black macule Cutis 97:384,406–407, 2016 Blue nevus JAAD 49:924–929, 2003; multiple congenital blue nevi BJD 152:391–393, 2005 Bowenoid papulosis – black papules; Ped Derm 2:297–301, 1985; Proc R Soc Med 68:345–346, 1975 Combined spindle and melanocytic nevus Combined type blue nevus Ped Derm 14:358–360, 1994 Deep penetrating nevus – black or darkly pigmented nevus of the head, neck, and scalp JAAD 71:1234–1240, 2014 Dermatofibrosarcoma protuberans – congenital blue-black patch JAAD 42:907–913, 2000; Bednar tumor (pigmented DFSP) Am J Surg Pathol 9:630–639, 1985

Lymphoma – intravascular large cell lymphoma – black macules JAAD 39:318–321, 1998; cutaneous extranodal natural killer/T-cell lymphoma – black nasal papules; edematous cheek; red plaques of the arms JAAD 70:716–723, 2014; folliculotropic cutaneous T-cell lymphoma – mimicking black dot tinea capitis Ped Derm 36:386– 387, 2019 Malignant blue nevus with a blue nevus – blue-black plaque with nodule Ped Derm 29:651–655, 2012 Pigmented epithelioid melanocytoma – blue-black papule BJD 174:1115–1117, 2016 Melanocytic nevus – congenital melanocytic nevus – giant black plaque NEJM 369:264, 2013; deep penetrating nevus JAAD 59:518–520, 2008; Ped Derm 25:97–98, 2008; black nail; traumatized nevus; desmoplastic hairless hypopigmented nevus BJD 148:1253–1257, 2003; large congenital nevi BJD 156:1251–1257, 2007; congenital nevus with black tuft of the hair – personal observation; melanocytic nevus in nail matrix JAAD 75:535–540, 2016 Melanoma – black vulva JAAD 81:1387–1396, 2019; nodular, congenital malignant melanoma BJD 151:693–697, 2004; of the lip BJD 152:1324–1326, 2005; black nail – subungual in situ melanoma BJD 174:935, 2016; JAMA 311:1350–1351, 2014; pigment-synthesizing (animal-type) melanoma JAAD 73:1031–1039, 2015; BJD 162:129–136, 2010; JAAD 62:324–329, 2010; AD 145:55–62, 2009; JAAD 54:547–548, 2006; Am J Surg Pathol 28:31–40, 2004; Histopathology 45:433–451, 2004; congenital pigment-synthesizing melanoma of the scalp (animal-type melanoma); black, pedunculated, ulcerated scalp nodule JAAD 62:324–329, 2010; seborrheic keratosis-like melanoma AD 143:373–376, 2007; acral lentiginous melanoma NEJM 373:1864, 2015; BJD 162:765–771, 2010; metastatic melanoma – exophytic black nodule Cutis 89:125–128, 2012; melanoma in situ – personal observation Nevus comedonicus Ped Derm 32:216–219, 2015; AD 139:93–98, 2003; extensive nevus comedonicus AD 116:1048–1050, 1980 Nevus of Ota – blue-black pigmentation Clin in Derm 37:468–486, 2019

Dermatosis papulosa nigra AD 89:655–658, 1964

Nevus sebaceus AD 140:1393–1398, 2004

Eccrine hidrocystomas JAAD 35:480–482, 1996

Pilomatrixoma AD 110:773–774, 1974

Eccrine poroma – blue-black pedunculated tumor of the chin BJD 152:1070–1072, 2005

Psammomatous melanotic schwannoma (Carney complex) AD 129:202–204, 1993

Epidermal nevus

Seborrheic keratosis

Epidermoid cyst – pink and black JAMADerm 151:1386–1388, 2015

Skin tag – necrosed due to torsion

Familial dyskeratotic comedones – discrete black papules with firm central keratotic plugs SkinMed 16:273–274, 2018; Indian Dermatol Online J 7:46–48, 2016

Spindle cell nevus of Reed – black papule or plaque – brown-black papule or nodule JAAD 71:1234–1240, 2014; Ped Derm 47:137– 139, 2002

Fibrous histiocytoma – aneurysmal variant; dark brown-black tender nodular mass of the thigh Ped Derm 35:836–838, 2018

Spitz nevus, including agminated Spitz nevi – black or black-pink nodule JAAD 52:S48–50, 2005; eruptive disseminated Spitz nevi; diffuse progressive proliferation of black papules JAMADERM 152:1273–1274, 2016; JAAD 57:519–523, 2007; Spitz tumors of

Granular cell schwannoma

“Black” Dermatologic Entities

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uncertain malignant potential (“STUMP” lesions) – black-brown papules JAAD 64:559–572, 2011

Peutz-Jeghers syndrome – blue-black pigmentation Clin in Derm 37:468–486, 2019

Spitzoid nevus – personal observation Squamous cell carcinoma – personal observation

Universal acquired melanosis (carbon baby) – deep black color of entire integument

Syringocystadenocarcinoma papilliferum – black cauliflower-like verrucous plaque JAAD 45:755–759, 2001

Xeroderma pigmentosum – black lentigines, melanoma JAAD 75:855–870, 2016

Trichofolliculoma – black pore Tumoral melanosis – multilobulated nodule as marker of regressed melanoma BJD 175:391–393, 2016; pigmented macule at the site of regression of melanoma BJD 155:627–628, 2006

TOXINS

PHOTODERMATOSES

TRAUMA

Ephelides

Black dot heel (talon noir) – hemorrhage in stratum corneum or dermal papillae JAAD 55:290–301, 2006; Trans St John’s Hosp Dermatol Soc 51:80–84, 1965

Favre-Racouchot syndrome – personal observation Melasma

Lead – black nails

Black palm Blast tattoos from black powder firearms JAAD 17;819–825, 1987

PRIMARY CUTANEOUS DISEASE

Burn blister with central necrosis

Acanthosis nigricans

Collier’s stripes (traumatic tattoos of coal miners) JAAD 20:137– 138, 1989

Acne vulgaris – open comedones (blackheads) Acquired universal melanosis (carbon baby syndrome) Ped Derm 31:620–622, 2014; AD 114:775–778, 1978 Alopecia areata – black dots (exclamation point hairs) Axillary granular parakeratosis – personal observation Black hairy tongue – personal observation Childhood flexural comedones – double opening AD 143:909–911, 2007 Chromhidrosis JAAD 52:89–91, 2005 Familial dyskeratotic comedones AD 105:249–251, 1972 Galactorrhea Giant comedone

Crack fingers – personal observation Flash pump dye laser therapy – blue-black pigmentation Clin in Derm 37:468–486, 2019 Frostbite – epidermal necrosis Hemorrhage – black nails Lead pencil injury Radiation – black nails; postradiation angiosarcoma Tongue necrosis – temporal arteritis (giant cell arteritis); endotracheal tube pressure Trauma with hemorrhagic crust Traumatic tattoo from swim goggles – personal observation

Hidradenitis suppurativa Hyperkeratosis of the nipple Ichthyosis – X-linked ichthyosis Idiopathic disseminated comedones Ped Derm 23:163–166, 2006 Lichen planopilaris Mal de Meleda – black pits Cutis 56:235–238, 1995 Pseudo-acanthosis nigricans – personal observation Reactive perforating collagenosis – black line Terra firme – personal observation

VASCULAR Angiokeratoma, solitary papular – blue-black BJD 157:210–212, 2007; plaque type JAAD 56:353–370, 2007; eruptive unilateral angiokeratomas AD 144:1663–1664, 2008; acral angiokeratomas of Mibelli in Turner’s syndrome – blue-black keratotic vascular papules Ped Derm 27:662–664, 2010 Angiosarcoma of the breast post-irradiation for breast cancer; black nodules JAAD 49:532–538, 2003

SYNDROMES

Cerebral cavernous malformations (cutaneous hyperkeratotic capillary-­venous malformation associated with familial cerebral cavernous malformations) (familial cerebral cavernomas) type 1 – autosomal dominant; localized dark red hyperkeratotic plaques; violaceous to blue-black plaques (malformations); red blanchable patches; red hyperkeratotic plaques; deep blue nodules; cutaneous venous malformations; mutations in CCM-1 gene which encodes for Krev-1 interaction TRAP 1 protein (KRIT1) Cutis 96:329–332, 2015; Ped Derm 26:666–667, 2009; JAAD 56:541–564, 2007; BJD 157:210–212, 2007; Hum Molec Genet 9:1351–1355, 2000; Ann Neurol 45:250–254, 1999; Lancet 352:1892–1897, 1998; CCM2 – malcaverin protein; CCM3 – PDCD10 protein

Atypical nevus syndrome

Cherry angioma, traumatized (Campbell de Morgan spots)

LEOPARD syndrome – café noir spots Ped Derm 25:444–448, 2008

Gangrene – black nails

Nevoid basal cell carcinoma syndrome Summer Meeting, American Academy of Dermatology, July 31, 2004; Int J Oral Maxillofac Surg 33:117–124, 2004; Am J Med Genet 69:299–308, 1997

Intravascular thrombosis (e.g., cryoglobulins) – epidermal necrosis

Trichostasis spinulosa JAAD 72:890–900, 2015; BJD 84:311–316, 1971

PSYCHOCUTANEOUS DISORDERS Delusions of parasitosis – debris presented by the patient Trichotillomania – personal observation

Kasabach-Merritt syndrome – blue-black tumid mass Ped Derm 34:261–265, 2017

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Lymphangioma circumscriptum – blue-black BJD 83:519–527, 1970

Silver amalgam tattoos

Martorell hypertensive ulcer (hypertensive ischemic leg ulcer) – violaceous black necrotic ulcer AD 146:961–968, 2010; JID 9:285–298, 1947; Proc Staff Meet Mayo Clin 21:337–346, 1946; Policlinico Barcelona 1(1):6–9, 1945

Smoker’s melanosis

Nevus flammeus with pyogenic granuloma – personal observation

Submucous hemorrhage Tattoos, ornamental Varicose veins

Polyarteritis nodosa – in children; fever, peripheral gangrene, black necrosis, livedo reticularis, ulcers, nodules, vesiculobullous lesions, arthralgia, nodules of the face and extremities, conjunctivitis JAAD 53:724–728, 2005; Ann Rheum Dis 54:134–136, 1995

BLASCHKO-ESQUE ENTITIES

Pyogenic granuloma

Am J Med Genet 85:324–329, 1999

Thrombosed capillary aneurysm – personal observation Vascular insufficiency – epidermal necrosis Verrucous hemangioma – linear along Blaschko’s lines JAAD 42:516–518, 2000

BLACK ORAL LESIONS Addison’s disease Amalgam tattoo Antimalarials (blue-gray) AZT (zidovudine) Black hairy tongue Blue nevus Carney complex Dalbavancin – related to vancomycin; black tongue Graphite tattoo – accidental injury with graphite pencil Hemangioma Hemochromatosis Hemorrhage – black papules of the buccal mucosa due to ITP Cutis 79:456–458, 2007 HIV disease Intramucous nevus Kaposi’s sarcoma Labial melanotic macule Laugier-Hunziker syndrome

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Localized unilateral chronic graft vs. host eruption after bone marrow transplant JAMADerm 154:494–495, 2018; JAAD 57:690– 699, 2007; BJD 147(Suppl):78–79, 2002; JAAD 37:1004–1006, 1997; AD 130:1206–1207, 1994; JAAD 28:888–892, 1993 Intraepidermal IgA dermatosis Lupus erythematosus – discoid LE Ped Derm 28:205–207, 2011; Ped Derm 24:125–129, 2007; Ped Derm 18:396–399, 2001; Ped Derm 16:128–133, 1999; BJD 139:307–310, 1998; Hautarzt 37:335–337, 1986; bullous LE Dermatology 199:60–62, 1999; Ped Derm 12:138–144, 1995; lupus profundus BJD 140:177–178, 1999; subacute cutaneous lupus erythematosus Eur J Dermatol 16:302– 310, 2006 Morphea JAAD 64:1012–1013, 2011; BJD 159:175–181, 2008; AD 143:953–955, 2007; Indian J Dermatol Venereol Leprol 71:421–422, 2005; nodular morphea AD 143:953–954, 2007; BJD 134:594–595, 1996; morphea/lichen sclerosus overlap AD 147:857–862, 2011 Pemphigus vulgaris Scleroderma – linear scleroderma; linear morphea Clin Exp Dermatol 24:467–468, 1999; JAAD 38:366–368, 1998; BJD 134:594–595, 1996 X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with upswept hair, flared eyebrows; female carriers display Blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

Lead poisoning (plumbism) – Burtonian line LEOPARD syndrome Linezolid – black tongue

CONGENITAL DISEASES

McCune-Albright syndrome

Aplasia cutis congenita Human Genet 90:467–471, 1992

Medications – minocycline, cyclophosphamide, busulfan, bleomycin, fluorouracil

Linear telangiectatic erythema and mild atrophoderma Cutis 39:69–70, 1987

Melanocytic nevi; compound nevus Singapore Dental J 37:33–35, 2006

Mosaic hypopigmentation – generalized Blaschko-esque hypopigmented patches NEJM 367:1245, 2012

Melanoma, gingival NEJM 369:1452, 2013 Neurofibromatosis – intraoral café au lait macule Normal variant Oral melanotic macule Oritavancin – related to vancomycin; black tongue Peutz-Jeghers syndrome Post-inflammatory hyperpigmentation – lichen planus, lichenoid reactions Pseudo-black hairy tongue – bismuth salicylate Cutis 105:288, 293, 2020

DRUG ERUPTIONS Linear fixed drug eruption Lichenoid drug eruption Dermatology 193:66–67, 1996; nicergoline (alpha-blocker)

INFECTIONS AND INFESTATIONS Measles Leprosy Int J Dermatol 58:729–732, 2019

Blaschko-esque Entities Scarlet fever in hypomelanosis of Ito Ped Derm 19:423–425, 2002

INFILTRATIVE DISORDERS Amyloidosis – primary cutaneous macular amyloidosis with Blaschko-­esque hyperpigmentation BJD 127:641–644, 1992; X-linked cutaneous amyloidosis (female carriers) Curr Prob in Derm VII:143–198, 1995; macular amyloid in incontinentia pigmenti-like pattern BJD 142:371–373, 2000

INFLAMMATORY DISEASES Blaschkitis (acquired relapsing self-healing Blaschko dermatitis) Eur J Dermatol 29:281–286, 2019; J Cut Pathol 41:950–954, 2014; J Dermatol 23:639–642, 1996; JAAD 31:849–852, 1994 Erythema multiforme J Eur Acad Dermatol Venereol 14:203–204, 2000

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Linear progressive fibromatosis Bull Soc Fr Derm Syph 83:278–279, 1976 Leiomyomas (piloleiomyomas) Melanocytic nevi – congenital, Spitz, blue, speckled lentiginous Acta DV 78:378–380, 1998; JAAD 27:853–854, 1992 Metastatic pancreatic cancer – inflammatory red plaque JAAD 31:877–80, 1994 Munro’s acne nevus – mosaic Apert’s syndrome; inflammatory acne lesions J Dtsch Dermatol Ges 6:721–728, 2009; Lancet 352:704– 705, 1998 Nevus angiolipomatosis Nevus comedonicus NEJM 372:2541, 2015; Ped Derm 21:432–439, 2004 Nevus corniculatus BJD 122:107–112, 1990 Nevus depigmentosus Nevus lipomatosus superficialis Nevus sebaceus and nevus sebaceus syndrome JAAD 44: 612–615, 2001

METABOLIC DISEASES

Nevus spilus Acta DV 78:378–380, 1998; JAAD 31:157–190, 1994

Xanthomas with hyperlipidemia

Nevus tricholemmocysticus – multiple pilar cysts; filiform hyperkeratoses of the face and arm, filiform papules, comedo-like plugs, osteomalacia, bone lesions; verrucous papules, yellow plaques, cysts; Blaschko distribution Ped Derm 30:261–261, 2013; Ped Derm 28:286–289, 2011; JAAD 57(Suppl):S72–77, 2007

NEOPLASMS Acantholytic dyskeratotic epidermal nevus JAMADerm 155:633– 635, 2019; JAMADerm 151:1259–1260, 2015 Achromic nevus Acquired dermal melanocytosis JAAD 31:157–190, 1994 Adnexal tumors Basal cell nevus, linear unilateral Cutis 78:122–124, 2006; Arch Dermatol Syphilol 65:471–476, 1952 Basaloid follicular hamartoma – guttate macules Int J Derm 44:361–365, 2005; congenital systematized basaloid follicular hamartoma with microphthalmia and hemimegalencephaly; unilateral linear hypopigmented macules and streaks Ped Derm 28:555–560, 2011 Becker’s nevus Cutis 75:122–124, 2005 Café au lait macules Acta DV 78:378–380, 1998 Connective tissue nevi Ped Derm 24:439–441, 2007; JAAD 54:S240, 2006 Cylindromas BJD 166:1376–1378, 2012 Eccrine nevus Eccrine poromas JAAD 31:157–190, 1994 Eccrine spiradenoma Ped Derm 26:180–183, 2009; Cutis 70:73–75, 2002; Ann DV 119:897–898, 1992 Epidermal nevi – linear and systematized (ichthyosis hystrix) (linear epidermolytic hyperkeratosis) BJD 122:417–422, 1990; JAAD 16:899–906, 1987; AD 120:223–236, 1984; acanthosis nigricans form of epidermal nevus JAAD 55:696–698, 2006 Follicular mucinosis Hair follicle nevus – skin-colored facial papules JAAD 46:S125–127, 2002 Hamartoma of follicular infundibulum Ichthyosis hystrix – personal observation Inflammatory linear verrucous epidermal nevus (ILVEN) – pink keratotic plaque Ped Derm 36:404–405, 2019; JAAD 49:976, 2003

Organoid nevus phakomatosis Pigmentary mosaicism – personal observation Palmoplantar verrucous nevus Porokeratosis, linear JAMADerm 155:548–555, 2019; Ped Derm 36:346–348, 2019; JAMADerm 150:194–196, 2014; JAAD 62:136–138, 2010; AD 142:1059–1064, 2006; J Dermatol 20:489–492, 1993; congenital linear porokeratosis Ped Derm 17:466–468, 2000; generalized porokeratosis AD 143:670–673, 2007; unilateral systematized linear porokeratosis JAAD 60:713714, 2009; porokeratosis of Mibelli; porokeratosis ptychotropica – Blaschko-esque, serpiginous, annular, hyperpigmented verrucous plaques of intertriginous areas and buttocks Ped Derm 37:248–250, 2020; JAMADerm 149:1099–1100, 2013; BJD 132:150–151, 1995 Porokeratotic eccrine and hair follicle nevus BJD 141:1092–1096, 1999 Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) – Blaschko red plaque with hyperkeratosis; mutation in GJB2 JAMADerm 151:638–641, 2015; Ped Derm 26:473–474, 2009; Ped Derm 24:162–167, 2007; Ped Derm 23:465–466, 2006; J Cutan Pathol 15:393–395, 1988; BJD 101:717–722, 1979; seen in KID syndrome Ped Derm 27:514–517, 2010; generalized porokeratotic eccrine ostial and dermal duct nevus – Blaschko-distributed verrucous plaques; non-scarring alopecia, hypohidrosis, teeth in disarray, deafness JAAD 59:S43–45, 2008 Porokeratotic adnexal ostial nevus cornifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic lesions with comedones; presents as red patch with red and atrophic linear and curvilinear erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAMADerm 154:1078–1079, 2018; JAAD 61:1060– 1069, 2009; BJD 103:435–441, 1980; BJD 101:717–722, 1979 Syringomas JAAD 31:157–190, 1994 Syringocystadenoma papilliferum JAAD 31:157–190, 1994

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Trichilemmal cyst nevus – multiple subcutaneous nodules with cystic lesions with and without comedones in Blaschko distribution, filiform hyperkeratoses JAAD 57:S72–77, 2007

Lichen striatus-like leukoderma J Eur Acad DV 10:152–154, 1998

Trichodiscomas

Linear atrophoderma of Moulin – acquired atrophic pigmented band-like lesions following Blaschko’s lines JAMADerm 156:581,583–584, 2020; JAAD 65:232–233, 2011; Eur J Dermatol 10:611–613, 2000; Int J Dermatol 39:850–852, 2000; JAAD 38:366–368, 1998; BJD 135:277–279, 1996; Ann DV 119:729– 736, 1992

Trichoepitheliomas Ped Derm 23:149–151, 2006; Verruciform xanthoma in epidermal nevus or CHILD syndrome

PRIMARY CUTANEOUS DISEASES Acne vulgaris – mosaic acne Lancet 352:704–705, 1998; Blaschko acne with F6FR2 mutation (Apert’s syndrome mutation) BJD 172:115–1127, 2015 Alopecia mucinosa Acta DV 72:155–156, 1992 Atopic dermatitis – loss of heterozygosity JAAD 57:690–699, 2007; JAAD 53:S221–224, 2005 Atrophoderma of Moulin – acquired atrophic pigmented band-like lesions following Blaschko’s lines; reticulated, atrophic, Blaschko lesions Ped Derm 31:373–377, 2014; JAAD 65:232–233, 2011; Ped Derm 22:350–354, 2005; JAAD 49:492–498, 2003; Eur J Dermatol 10:611–613, 2000; Int J Dermatol 39:850–852, 2000; JAAD 38:366– 368, 1998; BJD 135:277–279, 1996; Hautarzt 45:231–236, 1994; Ann DV 119:729–736, 1992; with lentigines BJD 163:1138–1140, 2010 Atrophoderma vermiculata Ped Derm 16:165, 1999 Blaschkoid dyspigmentation Ped Derm 31:471–476, 2014 Linear bullous ichthyosiform erythroderma Coexistent hyper- and hypopigmentation AD 132:1167–1179, 1996 Darier’s disease Cutis 86:224,237–238, 2010; BJD 149; 185–188, 2003; JAAD 32:284–286, 1995; BJD 105:207–214, 1981 Granuloma annulare BJD 157:1056–1058, 2007 Grover’s disease JAAD 47:319–320, 2002; JAAD 33:920–922, 1995

Linear and whorled nevoid hypermelanosis JAAD 60:328–331, 2009; Ped Derm 10:156–158, 1993; JAAD 19:1037–1044, 1988

Lipoatrophy – mosaic lipoatrophy JAAD 60:519–521, 2009 Psoriasis Clin Exp Dermatol 41:775–778, 2016; BJD 157:191–192, 2007; JAAD 50:S81–83, 2004; Ped Derm 21:70–73, 2004; Cutis 65:167–170, 2000; Ped Derm 13:219–221, 1996; pustular psoriasis JAAD 42:329–331, 2000; psoriasis occurring at the site of previous episode of lichen striatus Relapsing linear acantholytic dermatosis JAAD 33:920–922, 1995; BJD 112:349–355, 1985 Spiny hyperkeratosis – mosaic mutation in connexin 26 (GJB2) Ped Derm 33:322–326, 2016   Mutations in GJB2 Ped Derm 33:322–326, 2016    Autosomal recessive deafness    Autosomal dominant deafness   Bart-Pumphrey syndrome    Ichthyosis hystrix with deafness   Keratitis-ichthyosis-deafness syndrome    Palmoplantar keratoderma with deafness    Vohwinkel syndrome Tetragametic chimerism (“cutis bicolor”) – hyper- and hypopigmentation (Blaschko) AD 144:327–330, 2008 Vitiligo, segmental Blaschko-esque vitiligo JAAD 65:965–971, 2011

Hailey-Hailey disease

SYNDROMES

Heterochromic hair – Blaschko distribution Ped Derm 32:740–741, 2015

Bart’s syndrome – congenital localized absence of skin with dominant dystrophic epidermolysis bullosa Ped Derm 17:179–182, 2000

Hypermelanosis in a phylloid pattern – also Blaschko hyperpigmentation of the face; associated with spina bifida; musculoskeletal abnormalities JAAD 60:697–700, 2009 Hypomelanosis of Ito – lines of Blaschko Ichthyosis hystrix, epidermolytic hyperkeratosis with diffuse or striate PPK Kerinokeratosis papulosa (waxy keratoses of childhood) (nevus kerinokeratoticus) JAAD 50:S84–85, 2004; Clin Exp Dermatol 19:173–176, 1994 Lentigines within segmental achromic nevi JAAD 39:330–331, 1998 Lichen aureus Ped Derm 33:351–352, 2016; Ped Derm 28:727– 728, 2011 Lichen planus Ped Derm 27:34–38, 2010; JAAD 49:1190–1191, 2003; Ped Derm 19:541–545, 2002; Dermatology 202:340, 2001; BJD 135:275–276, 1996

Basaloid follicular hamartoma syndrome, segmental – osseous, dental, and cerebral anomalies Dermatology 218:221–225, 2009; Blaschko-­esque lesions of the face Clin Exp Dermatol 30:30–34, 2005 Brooke-Spiegler syndrome – linear papular eruption of eccrine spiradenomas Australas J Dermatol 44:144–148, 2003 CHILD syndrome(hemidysplasia, ichthyosiform erythroderma, unilateral limb defects (hypoplasia)) – X-linked dominant; unilateral inflammatory epidermal nevus or unilateral ichthyosiform erythroderma with skeletal abnormalities; linear hyperkeratotic plaques of the feet (unilateral inflammatory ichthyosiform nevus); ptychotropism, shortening and absence of the limbs, short stature mutations in NSDHL gene which encodes 3-beta hydroxysteroid dehydrogenase BJD 161:714–715, 2009;

Lichen planus pigmentosus SkinMed 11:96–103, 2013; JAAD 50:S78–80, 2004

AD 123:503–509, 1987; verruciform xanthoma – Blaschko red cobblestoned verrucous hypertrophic plaque of the vulva with linear extension onto leg Ped Derm 32:135–137, 2015

Lichen sclerosus et atrophicus J Korean Med Sci 19:152–154, 2004; JAAD 38:831–833, 1998; JAAD 43:903–904, 2000; JAAD 38:831–833, 1998

CHILD syndrome without congenital hemidysplasia – extensive lentigo simplex, linear epidermolytic nevus, and epidermolytic nevus comedonicus; mutation in KRT10 BJD 173:293–296, 2015

Lichen striatus Ped Derm 30:364–366, 2013; Ped Derm 21:197– 204, 2004; Ped Derm 13:95–99, 1996; Int J Dermatol 25:584–585, 1986; Ann Dermatol Syphilig 9:258, 1898; simultaneously in siblings Ped Derm 26:50–54, 2009

Chimerism (human chimera) – Blaschko hyperpigmentation Curr Prob in Derm VII:143–198, 1995; BJD 103:489–498, 1980

Blaschko-esque Entities Chromosomal mosaicism (segmental hypermelanosis) Textbook of Neonatal Dermatology, pp. 376–377, 2001; Curr Prob in Derm VII:143–198, 1995 Conradi-Hunermann syndrome (chondrodysplasia punctata – X-linked dominant) – linear and whorled hyperkeratosis, follicular atrophoderma of forearms in Blaschko distribution; linear atrophic lesions with follicular plugging of the scalp; cicatricial alopecia of the scalp; patchy patterned alopecia, generalized xerosis; cataracts, chondrodysplasia punctata; asymmetric shortening of long bones epiphyseal stippling, short stature, short limbs, kyphoscoliosis, craniofacial abnormalities; short arms and legs; cataracts – X-linked; mutation in emopamil-binding protein (EBP) Ped Derm 31:493–496, 2014; BJD 160:1335–1337, 2009; Curr Prob in Derm VII:143–198, 1995; AD 121:1064–1065, 1985; ichthyotic and psoriasiform lesions (Blaschko hyperkeratotic scaling), nail defects, cicatricial alopecia, follicular pitted scars, skeletal anomalies JAAD 33:356–360, 1995; Hum Genet 53:65–73, 1979; neonatal transient scaly plaques of the limbs, trunk, and scalp; scaly rash disappears in months leaving hypo- or hyperpigmented streaks with follicular atrophoderma and patchy scarring alopecia; CDPX2 – X-linked lethal in males; X-linked dominant (mosaic for emopamil-binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309– 1313, 2012

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of Wnt signaling proteins important in embryonic tissue development, fibroblast proliferation, and osteogenesis AD 148:85–88, 2012; protruding ears, midfacial hypoplasia, pointed chin, lower limb hypoplasia, Blaschko-esque atrophy, red and hypopigmented Blaschko streaks, painful exophytic granulation tissue, giant cell tumor of the bone (large subcutaneous nodule) BJD 160:1103– 1109, 2009; AD 143:109–114, 2007; JAAD 44: 612–615, 2001; JAAD 28:86–89, 1993; AD 86:708–717, 1962; male mosaic Goltz’s syndrome; Blaschko-linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011 Happle syndrome (X-linked chondrodysplasia punctata) – scalp dermatitis at birth; Blaschko hyperkeratoses, follicular atrophoderma, cicatricial alopecia Ped Derm 18:442–444, 2001; whorled ichthyosis Ped Derm 13:1–4, 1996 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas (Blaschko skin-colored or hyperpigmented papules); ipsilateral hypertrichosis; hypo- and hyperpigmentation; linear atrophoderma; osseous, dental, and/or cerebral defects; asymmetric shortened digits; mutation in SMO BJD 1108, 2016; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221–225, 2009; Acta DV 88:382–387, 2008

Male emopamil-binding protein disorder (MEND) with neurologic defects – severe neurologic defects, mild ichthyosis BJD 166:1309– 1313, 2012

Hypohidrotic ectodermal dysplasia – X-linked anhidrotic ectodermal dysplasia – female carrier or post-zygotic mutation in a male AD 136:217–224, 2000; Clin Genet 27:468–471, 1985

Depigmented hypertrichosis with dilated follicular pores, short stature, scoliosis, short broad feet, macrocephaly, dysmorphic facies, supernumerary nipple, and mental retardation (cerebralocular malformations) BJD 142:1204–1207, 2000

Hypomelanosis of Ito (incontinentia pigmenti achromians) – whorled depigmented patches in Blaschko pattern; associated musculoskeletal, teeth, eye, and central nervous system abnormalities; translocations between an X chromosome and an autosome NEJM 367:1245, 2012; Ped Derm 19:536–540, 2002; Indian J Ped 63:573–575, 1996; JID 103:141S–143S, 1994; JAAD 19:217–255, 1988; AD 119:391–395, 1983; J Pediatr 90:236–240, 1977; Jpn J Dermatol 61:31–32, 1951

Ectodermal dysplasia with immune deficiency Bolognia, p. 873, 2003 Encephalo-cranio-cutaneous lipomatosis Bolognia, p. 873, 2003 Erythrokeratoderma variabilis – ichthyosis hystrix-like appearance Clinics in Dermatol 23:23–32, 2005 Focal dermal hypoplasia, morning glory anomaly, and polymicrogyria – swirling pattern of hypopigmentation, papular hypopigmented and herniated skin lesions of the face, head, hands, and feet, basaloid follicular hamartomas, mild mental retardation, macrocephaly, microphthalmia, unilateral morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly Am J Med Genet 124A:202– 208, 2004 Naegeli-Franceschetti-Jadassohn syndrome Garcia-Hafner-Happle syndrome – fibroblast growth factor receptor 3 epidermal nevus syndrome BJD 166:202–204, 2012 Goltz’s syndrome (focal dermal hypoplasia) – asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberry-like papillomas of the lips, perineum, acrally, at perineum, buccal mucosa; xerosis; hypopigmented atrophic macules, Blaschko-­esque hyperpigmentation, yellow nodules of the hand, oligodontia, wide-spaced teeth, cleft hand, syndactyly (lobster claw foot), mammary hypoplasia, scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones; thin or atrophic nails Ped Derm 35:519–520, 2018; JAMADerm 152:713–714, 2016; AD 148:85–88, 2012; AD 143:109– 114, 2007; JAAD 25:879–881, 1991; AD 86:708–717, 1962; aplasia cutis congenita AD 145:218–219, 2009; male mosaic Goltz’s syndrome; Blaschko-linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011; unilateral focal dermal hypoplasia, unilateral – PORCN gene mutation; PORCN encodes O-acyltransferase involved in palmitoylation and secretion

Hypophosphatemic vitamin D-resistant rickets, precocious puberty, and epidermal nevus syndrome AD 133:1557–1561, 1997 Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome – X-linked; linear lesions with atrophy and scale in heterozygous women; mutation in MBTPS2 (membrane-bound transcription factor peptidase, site 2) (zinc metalloproteinase) BJD 163:886–889, 2010; Am J Med Genet 85:365–368, 1999 Incontinentia pigmenti – X-linked dominant; JAAD 81:1142–1149, 2019; AD 139:1163–1170, 2003; JAAD 47:169–187, 2002; Ped Derm 19:550–552, 2002; Curr Prob in Derm VII:143–198, 1995; Arch Dermatol Syphilol 38:57–69, 1938; Schweitz Med Wochenschr 56:404–405, 1926; involvement of NF-kappaB signaling Cell Signal 15:1–7, 2003; in males JAAD 56:264–267, 2007; JAAD 55:251–255, 2006; stage 4 – linear atrophic hairless patches, reticulated linear hyperpigmented patches JAAD 64:508–515, 2011; incontinentia pigmenti in male BJD 175:1059–1060, 2016 Kindler’s syndrome – personal observation Patau’s syndrome(non-mosaic trisomy 13) – parieto-occipital scalp defects, cleft lip/palate, Blaschko pigmentation, abnormal helices, low-set ears, loose skin of the posterior neck, simian crease of the hand, hyperconvex narrow nails, polydactyly, microcephaly, microphthalmia, anophthalmia, severe central nervous system anomalies, congenital heart defects, holoprosencephaly; death in first year Ped Derm 31:580–583, 2014; Am J Med Genet 143A:1739–1748, 2007; Ped Derm 22:270–275, 2005 Maffucci’s syndrome McCune-Albright syndrome – melanotic macules in Blaschko’s lines BJD 130:215–220, 1994; Int J Derm 23:370–375, 1984

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Menkes’ kinky hair syndrome – female carrier – X-linked recessive Microphthalmia with linear skin defects (MIDAS syndrome) (MLS syndrome, Xp deletion syndrome, Xp22.3 microdeletion syndrome) – Xp22.3 deletion – X-linked dominant; linear jagged skin defects of the scalp, face, neck, and occasionally upper trunk, Blaschko-esque depressed patches of the face, linear red atrophic patches (aplasia cutis-like), hyperpigmented Blaschko thin facial patches, reticulate skin defects of the head and neck, preauricular ear pit, severe short stature, congenital heart defects, agenesis of the corpus callosum, ambiguous genitalia, nail dystrophy, microphthalmia, sclerocornea; mutation in holocytochrome c synthase Ped Derm 29:217–218, 2012; Ped Derm 25:548–552, 2008; Ped Derm 20:153–157, 2003; JAAD 44: 612–615, 2001; Am J Med Genet 49:229–234, 1994 Mosaicism AD 129:1460–1470, 1993; Am J Hum Genet 45:193– 205, 1989 Neurofibromatosis, segmental (type V) Bolognia, p. 873, 2003 Nevoid basal cell carcinoma syndrome, including unilateral nevoid basal cell carcinoma syndrome Bolognia, p. 873, 2003; nevoid basal cell carcinoma syndrome with type 2 mosaicism – linear atrophic plaques; linear white papules; white papules and plaques; segmental hyper- and hypopigmented patches; Blaschko-esque atrophy and Blaschko-esque pits of the palms BJD 169:1342–1351, 2013 Nevus comedonicus syndrome Nevus sebaceus syndrome (Schimmelpenning syndrome)

Proteus syndrome – Blaschko epidermal nevi JAAD 56:353–370, 2007; JAAD 52:834–838, 2005; port-wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation AD 140:947–953, 2004; Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation Am J Med Genet 27:87–97, 1987; Pediatrics 76:984–989, 1985; Eur J Pediatr 140:5–12, 1983 Somatic mosaic RASopathy – epidermal nevi with cutaneous hypophosphatemia syndrome; FGF-R3 (phosphatonin); Blaschkoesque epidermal nevi JAAD 75:420–427, 2016 Sotos syndrome AD 132:1167–1170, 1996 Trisomy 13 – phylloid pigmentary pattern Ped Derm 14:278–280, 1998 Trisomy 14 – partial trisomy 14p Annual Meeting AAD 2000 Tuberous sclerosis – segmental ash leaf spot; leukodermic macules Mosaic Turner’s syndrome – Blaschko-distributed hyperpigmented macules BJD 175:1379–1381, 2016 Wells’ syndrome (eosinophilic cellulitis) Clin Exp Dermatol 24:449– 451, 1999; Blaschko-linear purpura J Drugs Dermatol 16:1036– 1038, 2017

Oculo-cerebro-cutaneous syndrome

Woolly hair nevus, Blaschko-linear pigmentation, epidermal nevi; HRAS mutation Ped Derm 36:368–371, 2019

Oral-facial-digital syndrome – X-linked dominant oral-facial-digital syndrome – hairless streaks along Blaschko’s lines Am J Med Genet 85:324–329, 1999; Ped Derm 16:367–370, 1999

X-linked hypohidrotic ectodermal dysplasia – female carriers, mosaicism – V-shaped hypopigmented linear lesions, patchy hypotrichosis, abnormal teeth Ped Derm 24:551–554, 2007

Pallister-Killian syndrome (Killian-Teschler-Nicola syndrome) – short neck; Blaschko hyperpigmentation, streaks of hypo- and hyperpigmentation, mental retardation, coarse facies with hypertelorism and prominent forehead, flat occiput, short nose with anteverted nostrils, flat nasal bridge, chubby cheeks, sparse eyelashes, long philtrum with thin upper lip, horizontal palpebral fissures, large low-set ears with thick lobules, sparse temporal hair and high frontal hairline, hypo- and hyperpigmentation, supernumerary nipples, Blaschko-linear hypopigmented bands of the face and shoulder; short neck; i(12p) (tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 26:195–196, 2009; Ped Derm 24:426–428, 2007; Ped Derm 23:382–385, 2006; Ped Derm 22:270–75, 2005; Ped Derm 17:151–153, 2000

X-linked reticulate pigmentary disorder with systemic manifestations (familial cutaneous amyloidosis) (Partington syndrome II) – X-linked; rare; Xp21–22; boys with generalized reticulated muddy brown pigmentation (dyschromatosis) with hypopigmented corneal dystrophy (dyskeratosis), coarse unruly hair, unswept eyebrows, silvery hair, hypohidrosis, recurrent pneumonia with chronic obstructive disease, clubbing; failure to thrive, female carriers with linear macular nevoid Blaschko-esque hyperpigmentation Ped Derm 22:122–126, 2005; Textbook of Neonatal Dermatology, p. 376, 2001; Semin Cut Med Surg 16:72–80, 1997; Am J Med Gen 10:65:1981

Partington syndrome – X-linked reticulate pigmentary disorder (amyloid) (amyloidosis carrier)

VASCULAR

Phakomatosis pigmentokeratotica – hemiatrophy NEJM 381:1458, 2019; BJD 155:225–226, 2006; AD 134:333–337, 1998; coexistence of a Blaschko-esque organoid nevus (nevus sebaceus/epidermal nevus) and connective tissue nevus SkinMed 11:125–128, 2013; Ped Derm 25:76–80, 2008; Ped Derm 22:44–47, 2005; AD 134:333–337, 1998 Phakomatosis pigmentovascularis – port-wine stain, oculocutaneous (dermal and scleral) melanosis, CNS manifestations; type I – PWS and linear epidermal nevus; type II – PWS and dermal melanocytosis; type III – PWS and nevus spilus; type IV – PWS, dermal melanocytosis, and nevus spilus; types II, III, and IV may also have nevus anemicus Ped Derm 21:642–645, 2004; J Dermatol 26:834–836, 1999; Ped Derm 15:321–323, 1998; Ped Derm 13:33–35, 1996; AD 121:651–653, 1985; Jpn J Dermatol 52:1–3, 1947 Poland syndrome with Blaschko-esque congenital nevi – unilateral chest wall and upper extremity hypoplasia due to subclavian artery hypoplasia; oligodactyly JAMADerm 150:1019–1020, 2014

Angiofibromas Angiokeratoma circumscriptum/verrucous hemangioma Angioma serpiginosum Ped Derm 20:167–168, 2003 Glomus tumors – congenital plaquelike glomuvenous malformations – targetoid blue Blaschko-esque plaques Cutis 84:16–18, 2009 Lymphangioma circumscriptum Lymphatic net-like malformation – Blaschko-esque livedo reticularislike lesions of the buttocks, thighs, and upper back; superficial lymphatic malformation high in dermis Cases of the Year, Pre-AAD Pediatric Dermatology Meeting Pigmented purpuric eruptions – lichen aureus – personal observation Unilateral nevoid telangiectasia Venous malformations Verrucous hemangioma JAAD 42:516–518, 2000; AD 132:703–708, 1996

Blindness, Cutaneous Manifestations

BLINDNESS, CUTANEOUS MANIFESTATIONS AUTOIMMUNE DISEASES Anti-laminin 332 mucous membrane pemphigoid – conjunctivitis with symblepharon; desquamative gingivitis BJD 169:100–105, 2013; JAAD 42:841–844, 2000 Antiphospholipid antibody syndrome – retinal arterial and venous thrombosis NEJM 379:2152–2159, 2018; presenting as transient visual loss Surv Ophthalmol 53:301–305, 2008 Atopic keratoconjunctivitis JAAD 70:569–575, 2014 Bardet-Biedl syndrome – postaxial polydactyly (ulnar), retinal dystrophy, retinitis pigmentosa, obesity, neuropathy, mental disturbance J Med Genet 36:599–603, 1999 Cicatricial pemphigoid (mucous membrane pemphigoid) Ped Derm 27:119–124, 2010; AD 138:370–379, 2002; ocular cicatricial pemphigoid AD 129:456–459, 1993; anti-epiligrin cicatricial pemphigoid JAAD 42:841–844, 2000 Epidermolysis bullosa acquisita JAAD 16:439–443, 1987; EBA with predominant IgA autoantibodies BJD 141:887–892, 1999; AD 135:954–959, 1999 GAPO syndrome (growth retardation, alopecia, pseudoanodontia, optic atrophy) – doughy appearance of the face with coarse wrinkling, full lips, cherubic appearance of jaws, frontal bossing, midfacial hypoplasia Genetic Skin Disorders, Second Edition, 2010, pp. 284–286 Linear IgA disease JAAD 30:355–357, 1994; JAAD 19:792–805, 1988; linear IgA disease vs. 290 kD-cicatricial pemphigoid-like syndrome JAAD 31:884–888, 1994; JAAD 20:761–770, 1989 Linear IgA disease vs. 290 kD-cicatricial pemphigoid-like syndrome JAAD 31:884–888, 1994; JAAD 20761–770, 1989 Lupus erythematosus – episcleritis NEJM 370:159–166, 2014; BJD 135:355–362, 1996; systemic – arterial and venous retinal occlusions; retinal vasculitis; antiphospholipid antibody and vaso-occlusive retinopathy NEJM 379:2152–2159, 2018; CMAJ 184:315–319, 2012; subacute cutaneous LE and keratoconjunctivitis sicca AD 128:1265–1270, 1992; discoid lupus erythematosus with punctate keratopathy or stromal keratitis Arch Ophthalmol 107:545–547, 1989 Mucous membrane pemphigoid J Ophthalmic Vis Res 14:195–210, 2019 Rheumatoid arthritis – episcleritis, scleritis NEJM 370:159–166, 2014; JAAD 46:161–183, 2002; peripheral ulcerative keratitis associated with neutrophilic disorders JAAD 40:331–334, 1999; bilateral corneal perforations NEJM 370:650, 2014 Scleroderma NEJM 370:159–166, 2014 Sjögren’s syndrome – keratoconjunctivitis sicca NEJM 370:159– 166, 2014 X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with unswept hair, flared eyebrows; female carriers display Blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

DEGENERATIVE DISORDERS Morgagnian cataract – yellow opacity NEJM 370:2326, 2014 Vitreochorioretinal degeneration – trichomegaly Ann Ophthalmol 8:811–815, 1976

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DRUG REACTIONS Antimalarials – cataracts, corneal deposits JAAD 70:821–838, 2014 Corticosteroids, topical – cataracts, glaucoma JAAD 70:821–838, 2014 Cyclosporine – cerebral blindness JAAD 70:821–838, 2014; posterior reversible encephalopathy syndrome Hong Kong Med J 15:153–154, 2009 Hydroxychloroquine – retinopathy Med J Aust 192:668–669, 2010 Interferon alpha – retinal hemorrhages, retinal microaneurysms JAAD 70:821–838, 2014 Retinoids – night and color blindness; cataracts JAAD 70:821–838, 2014; isotretinoin – blepharoconjunctivitis JAAD 19:209–211, 1988; night blindness due to hypovitaminosis A Australas J Dermatol 40:208–210, 1999; TNF inhibitors – endophthalmitis, uveitis, optic neuritis JAAD 70:821–838, 2014

EXOGENOUS AGENTS Crack cocaine, inhaled – toxic to corneal nerves, corneal anesthesia, exposure keratopathy NEJM 370:159–166, 2014 Methamphetamine, inhaled – toxic to corneal nerves, corneal anesthesia, exposure keratopathy NEJM 370:159–166, 2014

INFECTIONS AND INFESTATIONS Aspergillosis – angioinvasive fungus NEJM 379:2152–2159, 2018 Bacteria and fungi in inhalational drugs – corneal melting; Capnocytophaga, Candida albicans, Streptococcus mitis – corneal ulcers NEJM 370:159–166, 2014 Cat scratch disease – unilateral conjunctivitis with lymphadenopathy (Parinaud oculoglandular syndrome); optic nerve swelling, neuroretinitis with blindness JAAD 70:795–819, 2014 Cellulitis Cryptococcosis – cryptococcal meningitis in AIDS Rev Iberoam Micol 27:207–209, 2010 Cytomegalovirus infection – retinal vasculitis NEJM 379:2152–2159, 2018; retinitis Niger J Clin Pract 10:283–286, 2007 Erysipelas Herpes simplex virus – follicular conjunctivitis, episcleritis, keratitis, dendritic ulcer, anterior uveitis, central retinal vein occlusion, eczema herpeticum, periocular zosteriform eruption NEJM 370:159–166, 2014; J Virol 75:5069, 5075, 2001; Medicine 78:395–409, 1999; Arch Ophthalmol 107:1155–1159, 1989; Nephron 50:368–370, 1988; Am J Med Sci 277:39–47, 1979; scarring keratitis, dendritic corneal ulcers, conjunctivitis, blepharoconjunctivitis, stromal keratitis, retinitis JAAD 70:795–819, 2014 Herpes zoster – acute retinal necrosis, optic neuritis, acute glaucoma, episcleritis, scleritis, keratitis NEJM 369;255–263, 2013; Rook pp. 2992, 3006, 1998; J Laryngol Otol 100:337–340, 1986 Gnathostomiasis – consumption of raw fish, cutaneous migratory swellings, eosinophilia, acute unilateral visual loss J Neurophthalmol 26:184–186, 2006 Leprosy – exposure keratitis, corneal opacities, chronic uveitis JAAD 70:795–819, 2014; reversal reaction in leprosy – periarticular erythema and edema of the hand with edema of red plaques of the trunk; existing lesions become red and tumid with edema of the hands, neuritis, sensory and motor loss with foot drop, wrist drop, facial palsy, lagophthalmos, keratitis, and blindness JAAD 71:795– 803, 2014; lepromatous leprosy with infiltration of corneal nerves leading to anesthesia, infection, blindness Chin Med J (Engl)

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116:682–684, 2003; erythema nodosum leprosum with uveitis, edema, and hyperemia AD 138:1607–1612, 2002 Lyme disease – conjunctivitis leading to blindness; keratitis, optic neuritis, periorbital edema; uveitis JAAD 70:795–819, 2014; Br J Ophthalmol 107:581–587, 2000 Meningococcal conjunctivitis and cellulitis Pediatr 60:104–106, 1977; meningococcemia with orbital hemorrhage and DIC – periorbital edema and subconjunctival hemorrhage Eye 16:190–193, 2002; cryptococcal meningitis in AIDS – sudden blindness Rev Iberoam Micol 27:207–209, 2010; meningococcemia with disseminated intravascular dissemination J Foot Ankle Surg 49:489, 2010 Millipede bites – erythema, hyperpigmentation, blindness JAAD 67:347–354, 2012

Erythema multiforme major (Stevens-Johnson syndrome) – conjunctival scarring BJD 177:924–935, 2017; Am J Clin Dermatol 1:349–360, 2000 Polymyalgia rheumatica/temporal arteritis Vasa 34:128–130, 2005 Sarcoid – anterior uveitis, vitritis, posterior uveitis, retinal vasculitis NEJM 379:2152–2159, 2018; conjunctivitis, iridocyclitis, uveitis; Lofgren’s syndrome – erythema nodosum, bilateral hilar adenopathy, acute iridocyclitis; Heerfordt’s syndrome (uveoparotid fever) – uveitis, parotid gland enlargement, fever, cranial nerve (facial nerve) palsies Clin Dermatol 4:129–135, 1986 Stevens-Johnson syndrome Ulcerative colitis – corneal ulceration NEJM 370:159–166, 2014

Moraxella liquefaciens NEJM 370:159–166, 2014 Mycobacterium tuberculosis – granulomatous intraocular disease; severe inflammatory retinal vasculitis (Eales’s syndrome) NEJM 379:2152–2159, 2018; tuberculous meningitis South Med J 100:228–229, 2007; ocular tuberculosis Niger J Clin Pract 9:68–76, 2006 Myiasis – Hypoderma tarandi; bumblebee-like fly of subarctic regions; eggs deposited on reindeer (caribou); larvae penetrate skin, hatch, and result in migratory swellings; ophthalmomyiasis may result in blindness NEJM 367:2456–2457, 2012; JAAD 58:907–926, 2008 Onchocerciasis Onchocerciasis – corneal inflammation surrounding dead microfilariae leads to punctate keratitis, then sclerosing keratitis or iridocyclitis and blindness Clin Dermatol 24:176–180, 2006; edema and injection leading to scarring keratitis; river blindness JAAD 73:929–944, 2015; JAAD 70:795–819, 2014 Schistosomiasis – uveitis and subretinal granulomas JAAD 70:795–819, 2014 Staphylococcus aureus – keratitis, scleritis, and episcleritis NEJM 370:159–166, 2014 Streptococcus pneumoniae NEJM 370:159–166, 2014 Syphilis – secondary syphilis with retinal vasculitis NEJM 379:2152– 2159, 2018; optic neuritis NEJM 363:865–874, 2010; Sex Transm Infec 86:512–513, 2010; syphilitic uveitis Ann Dermatol 21:399–401, 2009 Toxoplasmosis – retinal vasculitis NEJM 379:2152–2159, 2018 Varicella-zoster virus – occlusive retinal vasculitis, episcleritis, conjunctivitis, stromal keratitis, neurotrophic keratitis, uveitis, retrobulbar optic neuritis, retinitis, scleritis, choroiditis NEJM 379:2152–2159, 2018; JAAD 70:795–819, 2014; congenital cataracts NEJM 375:1468, 2016

INFILTRATIVE DISEASES Juvenile xanthogranuloma – hemorrhage into anterior chamber, uveitis, iritis, congenital glaucoma with conjunctival hyperemia Ped Derm 26:232–234, 2009 Xanthoma disseminatum – multiple cerebral and cerebellar lesions progressing to blindness JAAD 23:341–346, 1990

INFLAMMATORY DISORDERS Ankylosing spondylitis – associated scleritis or peripheral ulcerative keratopathy NEJM 370:159–166, 2014; Rheum Dis Clin North Am 33:835–854, 2007

METABOLIC DISORDERS Diabetes mellitus – diabetic retinopathy Clin Ophthalmol 4:1291– 1298, 2010 Homocystinuria – cystathionine beta-synthase deficiency; severe myopia; facies – midfacial hypoplasia, dental crowding, protruding maxilla, frontal bossing, downward lateral canthi, symmetric hypoplasia of the midface and maxilla, relative mandibular hyperplasia; pectus excavatum and pectus carinatum, severe myopia NEJM 375:1879–1890, 2016 Hypoplasminogenemia – autosomal recessive; red eyes, oral ulcers, gingival edema; ligneous conjunctivitis with red eyes, ligneous periodontitis, blindness, tooth loss; decreased wound healing JAMADerm 150:1227–12228, 2014 Porphyria – congenital erythropoietic porphyria – blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, keratoconjunctivitis, cataracts JAAD 67:1093– 1110, 2012; Semin Liver Dis 2:154–163, 1982 Protein C or S deficiency – retinal vein thrombosis NEJM 379:2152– 2159, 2018 Tyrosinemia type II (Richner-Hanhart syndrome) Vitamin A deficiency (phrynoderma) – night blindness, bilateral dry eyes, punctate keratitis, corneal neovascularization, and keratomalacia (corneal melting), squamous metaplasia with hyperkeratinization; with xerophthalmia NEJM 382:1629–1637, 2020; J Inv Med High Impact Case Rep Vol 7, 2019; NEJM 370:159–166, 2014; Clin in Derm 17:457–461, 1999; NEJM 331:551, 1994

NEOPLASMS Basal cell carcinoma – invasion by tumor JAAD 70:821–838, 2014; BJD 127:164–167, 1992 Basal cell nevus syndrome – cataracts, retinal hamartomas JAAD 70:795–819, 2014 Leukemia – juvenile myelomonocytic leukemia Ann Hematol 78:568–570, 1999 Lymphoma – cutaneous T-cell lymphoma – uveitis, retinal vasculitis JAAD 70:821–838, 2014 Lymphoma – HTLV-I/II leukemia/lymphoma – conjunctivitis JAAD 38:502, 1998; cutaneous T-cell lymphoma – keratitis, uveitis Arch Ophthalmol 99:272–274, 1981 Melanoma – uveal melanoma Indian J Ophthalmol 57:223–225, 2009; ocular metastasis from cutaneous melanoma Optometry 80:572–578, 2009 Squamous cell carcinoma – patient with epidermodysplasia verruciformis JAAD 49:S262–264, 2003

Blindness, Cutaneous Manifestations

PARANEOPLASTIC DISORDERS Melanoma-associated retinopathy (MAR) – night blindness, light sensations, visual loss, defect in visual fields BJD 149:74–78, 2003 Paraneoplastic pemphigus – conjunctivitis Cutis 61:94–96, 1998; Dermatol Clin 10:557–571, 1992; NEJM 323:1729–1735, 1990

PRIMARY CUTANEOUS DISEASES Acne rosacea – rosaceal conjunctivitis Eur J Ophthalmol 10:11–14, 2000

SYNDROMES Alström syndrome – dermatologic and pigmentary retinopathy or cone-rod dystrophy; acanthosis nigricans, alopecia, hirsutism; mutation in ALMS1; subcapsular cataracts, cone-rod dystrophy, photophobia, nystagmus, blindness BJD 164:878–880, 2011 ANCA-associated vasculitis NEJM 379:2152–2159, 2018 Behcet’s disease – severe necrotizing retinal vasculitis NEJM 379:2152–2159, 2018; relapsing iritis, conjunctivitis, episcleritis, keratitis, blindness Semin Cutan Med Surg 20:53–57, 2001; JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999 Blau syndrome J Clin Rheum 6:30–34, 2000 Blue rubber bleb nevus syndrome – bleeding in cavernomas with resultant cortical blindness Australas J Dermatol 46:192–195, 2005 Cerebro-oculo-facio-skeletal syndrome (in Aboriginal families) – microcephaly, facies – micrognathia, small eyes, enlarged ears, bulbous nose, prominent nasal bridge, microphthalmia with poor vision, cataracts, blepharophimosis, short palpebral fissures, onychogryphosis, photosensitivity, mental retardation, hyperkinesis, failure to thrive, developmental delay, hypotonia, orthopedic anomalies (kyphoscoliosis), joint contractures; overhanging upper lip, small jaw JAAD 75:873–882, 2016; Ped Derm 26:97–99, 2009; Atlas of Clinical Syndromes: A Visual Aid to Diagnosis, 1992, p. 556; JAMADerm 149:1414–1418, 2013 Chediak-Higashi syndrome – decreased vision JAAD 70:795–819, 2014 Cockayne syndrome – xerosis with rough, dry skin, anhidrosis, erythema of the hands, hypogonadism; autosomal recessive; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, prematurely aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects including retinal degeneration, demyelination JAMADerm 149:1414–1418, 2013; Ped Derm 20:538–540, 2003; Am J Hum Genet 50:677–689, 1992; J Med Genet 18:288–293, 1981; bird-headed dwarfism Epidermolysis bullosa acquisita JAAD 16:439–443, 1987; EBA patients with predominant IgA autoantibodies more frequently develop severe ocular involvement BJD 141:887–892, 1999: AD 135:954–959, 1999 Hermansky-Pudlak syndrome – decreased vision JAAD 70:795– 819, 2014 Hurler’s syndrome (mucopolysaccharidosis type I–H) – disorder of glycosaminoglycans accumulation; autosomal recessive; coarse facies, macroglossia, short stature, macrocephaly, hepatosplenomegaly, hernias, corneal clouding, vision and hearing loss; cardiac anomalies; respiratory infections; alpha-L-iduronate deficiency Ped Derm 33:594–601, 2016; Atlas of Clinical Syndromes: A Visual Aid to Diagnosis, 1992, pp. 118–119

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Hypotrichosis with juvenile macular dystrophy – autosomal recessive; hypotrichosis, short scalp hair, progressive macular dystrophy; blindness in second to fourth decades of life Dermatology 220:208–212, 2010; Clin in Dermatol 23:47–55, 2005 Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked recessive; linear plantar hyperkeratosis of the heels; linear hairless scalp area in female carriers; ichthyosis, atopic dermatitis, alopecia, follicular papules, nail dystrophy, hyperextensible joints, photophobia, cheilitis, growth and psychomotor retardation, recurrent respiratory and skin infections, cryptorchidism, muscular hypotonia, skeletal abnormalities, inguinal hernia, congenital aganglionic megacolon, corneal vascularization and blindness; mutation in MBTPS2 (membrane-bound transcription factor protease, site 2) (zinc metalloprotease) JAAD 64:716–722, 2011; Am J Med Genet 85:365–368, 1999 Incontinentia pigmenti JAAD 81:1142–1149, 2019; JAAD 75:1101– 1117, 2016 Keratosis-ichthyosis-deafness (KID) syndrome – reticulated severe diffuse hyperkeratosis of the palms and soles, well-marginated, serpiginous erythematous verrucous plaques, perioral furrows, leukoplakia, sensory deafness, photophobia with vascularizing keratitis, blindness Ped Derm 29:349–357, 2012; Ped Derm 23:81–83,2006; JAAD 23:385–388, 1990; AD 123:777–782, 1987; AD 117:285–289, 1981; neovascularization of the cornea JAAD 70:795–819, 2014 Laryngo-onycho-cutaneous syndrome – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of the mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3 (LAMA3A) BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedica 2:15–25, 1986 Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) – autosomal recessive; coarse facies; corneal clouding, endocardial fibroelastosis with cardiomyopathy, dysostosis multiplex Ped Derm 33:594–601, 2016; Atlas of Clinical Syndromes: A Visual Aid to Diagnosis, 1992, pp. 126–127 McCune-Albright syndrome – visual loss from craniofacial fibrous dysplasia; café au lait macules; premature puberty Ped Derm 31:80–82, 2014 Morquio’s syndrome (mucopolysaccharidosis type IV) – autosomal recessive; short neck, skeletal abnormalities, corneal clouding, cardiac valvulopathies, odontoid hypoplasia, hypermobile joints Ped Derm 33:594–601, 2016 Neurofibromatosis type I – acute monocular blindness due to malignant melanocytic schwannomas J Neurooncol 76:277–281, 2006 Pseudoxanthoma elasticum – presenting with blindness; angioid streaks J R Soc Med 82:627–628, 1989 Richner-Hanhart syndrome (tyrosinemia type II) – bullae of the palms and soles; palmoplantar keratoderma; photophobia; excessive tearing; pseudodendritic corneal ulcers Rothmund-Thomson syndrome – juvenile subcapsular cataracts JAAD 75:855–870, 2016 Scheie syndrome (mucopolysaccharidosis type I) – autosomal recessive; alpha-L-iduronate deficiency; disorder of glycosaminoglycans; corneal clouding, joint stiffness, cardiac valvular disease Ped Derm 33:594–601, 2016

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von Hippel-Lindau syndrome – blindness due to retinal hemangioblastoma, café au lait macules, capillary malformations JAAD 74:231–244, 2016

Leprosy – lagophthalmos (inability to completely close the eyes); corneal and conjunctival anesthesia (facial and trigeminal nerve involvement)

Xeroderma pigmentosum – superficial ulcers of the eyelids leading to scarring, ectropion; photophobia, conjunctivitis, symblepharon, neurologic abnormalities Adv Genet 43:71–102, 2001; Hum Mutat 14:9–22, 1999; Mol Med Today 5:86–94, 1999; Derm Surg 23:447–455, 1997; Dermatol Clin 13:169–209, 1995; Recent Results Cancer Res 128:275–297, 1993; AD 123:241–250, 1987; Ann Int Med 80:221–248, 1974; XP variant AD 128:1233–1237, 1992; corneal opacification, exposure keratitis JAAD 70:795–819, 2014

Mucormycosis

TOXINS Thallium poisoning – visual impairment JAMADerm 152:724–726, 2016

Toxoplasmosis – infectious posterior uveitis

BLUE LUNULAE/BLUE NAILS Alkaptonuria (ochronosis) Amodiaquine Clin Derm 37:468–486, 2019 Argyria Br J Dermatol Syph 47:441–455, 1935; galvanizers (silver or cyanide) Bleomycin, dactinomycin, vinblastine combination Arch Int Med 136:1117–1118, 1976 Bony deformity and verrucae J Drugs Dermatol 12:223–226, 2013 Chloroquine AD 88:419–426, 1963

VASCULAR DISORDERS

Cisplatin, ifosfamide, temozolomide, vincristine J Drugs Dermatol 12:223–226, 2013

Cholesterol emboli NEJM 379:2152–2159, 2018

Cupric acid

Eosinophilic granulomatosis with polyangiitis Am J Case Rep 17:864–868,2016

Cyclophosphamide, dacarbazine, doxorubicin, vincristine JAAD 34:943–953, 1996

Granulomatosis with polyangiitis – bilateral central retinal artery occlusions J Neuroophthalmol 25:29–32, 2005; corneal ulceration NEJM 370:159–166, 2014

Docetaxel SkinMed 8:179–180, 2010

Infantile hemangiomas – of eyelid, intraconal, extraconal Sem Cut Med Surg 35:108–116, 2016; periocular J Plast Reconstr Aesthet Surg 63:1–8, 2010

Enchondromas 5-Fluorouracil, cyclophosphamide, doxorubicin JAAD 34:943–953, 1996 Formaldehyde nail hardeners

PHACES syndrome – morning glory disc anomaly; microphthalmia JAAD 70:821–838, 2014

Hemochromatosis

Platelet-fibrin emboli NEJM 379:2152–2159, 2018

Hereditary acrolabial telangiectasia AD 115:474–478, 1979

Stroke

HIV infection

Sturge-Weber syndrome – decreased vision JAAD 70:821–838, 2014

Hydroxyurea J Dermatol 30:628–630, 2003

Temporal arteritis (giant cell arteritis) – ischemic optic neuropathy, occlusion of central retinal and cilioretinal arteries, ocular ischemic and infarction syndromes, and posterior ischemic optic neuropathy NEJM 371:1652, 2014; NEJM 371:50–57, 2014; Rheum Dis Clin North Am 27:781–797, 2001; Am J Ophthalmol 125:509–520, 1998

Hemoglobin M disease Bull Yamaguchi Med Sch 14:141, 1967

Idiopathic Mepacrine BJD 130:794–795, 1994 Mercury bichloride, topical Metal cleaners Clin Derm 37:468–486, 2019 Minocycline Am J Med 119:832–834, 2006 Myxoid cyst Clin in Derm 37:468–486, 2019

BLINDNESS AND CUTANEOUS ULCERS/ESCHARS Acanthamoeba – keratitis in contact lens wearers; ocular pain, photophobia, red eye, excessive tearing, reduced vision Antiphospholipid antibody syndrome Calciphylaxis Cholesterol emboli Cocaine abuse – levamisole-induced cutaneous vasculopathy Cryofibrinogenemia Cryoglobulinemia Cytomegalovirus infection Ecthyma gangrenosum – bacterial keratitis, scleral abscess, endophthalmitis Granulomatous vasculitis – granulomatous inflammation of orbit, optic nerve leading to ophthalmoplegia and blindness; associated with lymphoproliferative disorders or granulomatosis with polyangiitis Herpes simplex virus – dendritic corneal ulcer

Normal variant J Drugs Dermatol 12:223–226, 2013 Subungual onycholemmal cyst Cutis 98:102–110, 2016 Oxalic acid in radiators Clin Derm 37:468–486, 2019 Paint remover Clin Derm 37:468–486, 2019 Pernicious anemia, congenital Phenolphthalein (Ex-Lax) BJD 43:186–187, 1931 Picric acid Pseudo-blue lunulae SkinMed 8:363–364, 2010 PUVA Quinacrine, campoquine Clin Derm 37:468–486, 2019 Rispiradone Clin Derm 37:468–486, 2019 Subungual hematoma Thallium Wilson’s disease (hepatolenticular degeneration) JAMA 166:904– 906, 1958 Zidovudine (AZT) Clin Derm 37:468–486, 2019; JAAD 22:327–330, 1990

Blue Sclerae

BLUE SCLERAE Oral Surg Oral Med Oral Pathol Oral Radiol 126:252–263, 2018  Caplan syndrome Clin Derm 37:468–486, 2019  Collagen necrosis due to autoimmune disorders (rheumatoid arthritis)   Newborn infants Clin Derm 37:468–486, 2019  Glaucoma   High myopia   Senile hyaline plaque – blue sclerae at 3 and 9 o’clock  Chlorpromazine – blue-gray pigmentation; corneal and lens opacities Cutis 93:247–250, 2014  Corticosteroids Clin Derm 37:468–486, 2019  Minocycline – blue or blue-gray pigmentation Clin in Derm 37:468–486, 2019; Arthr Rheum 50:3698–3701, 2004  Mitoxantrone Clin Derm 37:468–486, 2019  Ochronosis (alkaptonuria) JAMADerm 152:465–466, 2016; NEJM 347:2111–2121, 2003   Ehlers-Danlos syndrome type VII Clin Derm 37:468–486, 2019  Ezogabine – blue-gray mucocutaneous pigmentation; black pigment of the conjunctivae JAMADerm 150:984–989, 2014   Hallermann-Streiff syndrome Clin Derm 37:468–486, 2019   Kabuki syndrome Clin Derm 37:468–486, 2019   Laron syndrome Clin Derm 37:468–486, 2019   Loeys-Dietz syndrome type 1 Clin Derm 37:468–486, 2019   Marshall-Smith syndrome Clin Derm 37:468–486, 2019   Osteogenesis imperfecta Clin Derm 37:468–486, 2019   POEMS syndrome Clin Derm 37:468–486, 2019

OTHER CAUSES   Argyria – blue-gray pigmentation Clin in Derm 37:468–486, 2019  Chrysiasis Clin Derm 37:468–486, 2019   HIV infection Clin Derm 37:468–486, 2019  Hyperhomocysteinemia Clin Derm 37:468–486, 2019   Iron deficiency Clin Derm 37:468–486, 2019  Melanoma Clin Derm 37:468–486, 2019   Myasthenia gravis Clin Derm 37:468–486, 2019   Nevus of Ota Clin Derm 37:468–486, 2019  Ochronosis Clin Derm 37:468–486, 2019

BLUE SPOTS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

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of nasolacrimal duct Ped Derm 28:70–72, 2011; JAAD 61:1088– 1090, 2009   vs. Encephalocele   Nasal glioma   Infantile hemangioma   Congenital hemangioma   Dermoid cyst Dermoid cyst – blue nodule JAAD 46:934–941, 2002 Embryonal rhabdomyosarcoma Ped Derm 26:473–474, 2009 Ewing’s tumor, congenital Ped Derm 26:473–474, 2009 Fibrous hamartoma of infancy – blue plaque of the neck AD 144:547–552, 2008 Heterotopic brain tissue (heterotopic meningeal nodules) – blue-red cystic mass with overlying alopecia Dermatol Therapy 18:104–116, 2005; JAAD 46:934–941, 2002; bald cyst of the scalp with surrounding hypertrichosis AD 131:731, 1995; JAAD 28:1015, 1993; BJD 129:183–185, 1993; AD 125:1253–1256, 1989 Mucocele of lacrimal sac – blue cystic swelling below medial canthus Infantile hemangioma – blue blush of sacrum with pit – dermosacral fistula Ped Derm 37:40–51, 2020 Infantile myofibromatosis – blue nodule of neonate Soc Ped Derm Annual Meeting, July 2006 Infantile myofibrosarcoma – blue nodule of neonate Soc Ped Derm Annual Meeting, July 2006 Leukemia, congenital Ped Derm 26:473–474, 2009; acute monocytic leukemia Ped Derm 30:387–388, 2013 Lymphoma, congenital Ped Derm 26:473–474, 2009 Meningothelial hamartoma (rudimentary meningocele) – alopecic fibrotic blue-purple plaque of the scalp Ped Derm 28:677–680, 2011 Dermal melanocytosis; congenital, persistent Ped Derm 36:755– 757, 2019; JAAD 16:788–792, 1987; Clin Pediatr 20:714–719, 1981; J Dermatol 7:449–450, 1980; superimposed Mongolian spots Ped Derm 25:233–235, 2008; blue-green pigmentation Ped Derm 30:683–688, 2013 Nasal encephalocele Dermatol Therapy 18:104–116, 2005 Nasal glioma Dermatol Therapy 18:104–116, 2005 Neuroblastoma – blue nodule of neonate Soc Ped Derm Annual Meeting, July 2006 Rhabdoid tumor – blue nodules Ped Derm 28:85–93, 2011; rhabdomyosarcoma Undifferentiated juvenile sarcoma – blue nodule of neonate Soc Ped Derm Annual Meeting, July 2006

Autoerythrocyte sensitization Graft vs. host disease Lupus erythematosus, neonatal

CONGENITAL ANOMALIES Branchial cleft cyst (cystic papule) AD 128:1395–1400, 1992 Cephalocele – includes anterior encephalocele JAAD 51:577–579, 2004; meningomyelocele; blue nodule with overlying hypertrichosis JAAD 46:934–941, 2002; AD 137:45–50, 2001 Congenital hemangioma of the eccrine sweat gland Ped Derm 10:341–343, 1993 Dacryocystocele – congenital blue/red firm nodule of medial canthus or medial lower eyelid due to congenital obstruction

DEGENERATIVE DISEASES Digital mucous pseudocyst – Arthr Rheum 20:997–1002, 1977

DRUG-INDUCED Acrocyanosis  Acetylcholine – blue toes JAAD 64:1218–1219, 2011  Amphetamines – Raynaud’s phenomenon JAAD 59:633–653, 2008; amphetamine and methylphenidate; mixed amphetamine salts for attention deficit disorder (Adderall) – blue toes JAAD 64:1218–1219, 2011  Amphotericin B deoxycholate – blue toes JAAD 64:1218–1219, 2011

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 Beta–adrenergic blockers – Raynaud’s phenomenon JAAD 59:633–653, 2008  Blasticidin (fungicide) Vet Hum Toxicol 38:107–112, 1996  Bleomycin – Raynaud’s phenomenon JAAD 59:633–653, 2008;

Doxorubicin, liposomal – blue-gray hyperpigmentation JAAD 58:545–570, 2008

Clin Rheumatol 18:422–424, 1999; JAAD 33:851–852, 1995; AD 107:553–555, 1973  Buprenorphine – intra-arterial injection AD 138:1296–1298, 2002  Butyl nitrite abuse AD 135:90–91, 1999  Cetirizine – blue toes JAAD 64:1218–1219, 2011  Cisplatin – Raynaud’s phenomenon JAAD 59:633–653, 2008; Eur Heart J 9:552–561, 1988  Coumarin purple toe syndrome JAAD 61:325–332, 2009; Thromb Haemost 78:785–790, 1997; Ann Int Med 113:893–895, 1990  Crack inhalation – acrocyanosis, necrotizing livedo reticularis (livedo racemosa), and muscle infarction Ann Int Med 108:843, 1988  Cyclosporine – Raynaud’s phenomenon JAAD 59:633–653, 2008  d-Lysergic acid amide and d-lysergamide (LSA) – blue toes JAAD 64:1218–1219, 2011  Epinephrine Am J Emerg Med 8:46–47, 1990  Ergots – Raynaud’s phenomenon JAAD 59:633–653, 2008  Imipramine Arch Dis Child 63:204–205, 1988  Interferon alpha – Raynaud’s phenomenon JAAD 59:633–653, 2008  Lysergic acid diethylamide (LSD) – blue toes JAAD 64:1218– 1219, 2011  Norepinephrine – blue toes JAAD 64:1218–1219, 2011  Oxymetazoline – intra-arterial injection AD 138:1296–1298, 2002  Phenylephrine-induced microvascular occlusion syndrome – livedo racemosa, acral cyanosis and necrosis with hemorrhagic bullae AD 143:1314–1317, 2007  Pseudoephedrine/phenylephrine – blue toes JAAD 64:1218– 1219, 2011  Psilocybin – blue toes JAAD 64:1218–1219, 2011  Quinine sulfate Hautarzt 51:332–335, 2000  Oxymetazoline – intra-arterial injection AD 138:1296–1298, 2002  Tetrahydrozoline – blue toes JAAD 64:1218–1219, 2011  Vasculitis, drug-induced AD 138:1296–1298, 2002  Vinblastine – Raynaud’s phenomenon JAAD 59:633–653, 2008  Warfarin – blue toes JAAD 64:1218–1219, 2011

Fixed drug eruptions

Ametantrone Clin Derm 37:468–486, 2019

Psychotropic drugs, including chlorpromazine, thioridazine, imipramine, desipramine hydrochloride, amitriptyline hydrochloride – gray to blue-black hyperpigmentation JAMADerm 150:984–989, 2014

Amiodarone – blue, blue-gray, slate gray JAMADerm 150:984–989, 2014; AD 144:92–96, 2008; Clin Cardiol 19:592–594, 1996; JAAD 11:898–900, 1984; BJD 110:451–456, 1984

Ezogabine – blue-gray mucocutaneous pigmentation; black pigment of the conjunctivae JAMADerm 150:984–989, 2014 Gold (chrysiasis) – blue-gray pigmentation JAMADerm 150:984– 989, 2014; BJD 133:671–678, 1995 Haloperidol – blue oral mucosa Clin Derm 37:468–486, 2019 Hydroxychloroquine – blue-green pigmentation of shins JAMADerm 149:935–940, 2013; gray to blue-black pigmentation JAMADerm 150:984–989, 2014; blue-black pigmentation Imipramine JAAD 25:357–361, 1991 Imatinib – blue-gray hyperpigmentation JAAD 77:902–910, 2017 Iron Levofloxacin – blue-gray pigmentation JAMADerm 149:1111–1112, 2013; blue-black macules of the hands and legs AD 143:1441– 1446, 2007 Mercury Metoclopramide – blue oral mucosa Clin Derm 37:468–486, 2019 Methylene blue by intravenous injection – blue macules or blue skin; mimics cyanosis Cutis 63:103–106, 1999; NEJM 320:1756–1757, 1989 Minocycline – blue-black scleral, dental, and blue-gray cutaneous pigmentation JAMADerm 151:1026–1028, 2015; JAAD 68:879–881, 2013; JAAD 65:689–697, 2011; Cutis 84:22–26, 2009; Rook p. 1960, 1998, Sixth Edition; Am J Ophthalmol 125:396–397, 1998; JAMA 220:1323–1335, 1972; including pseudo-Mongolian spot AD 128:565–566, 1992; post-acne osteoma cutis treated with minocycline JAAD 24:851–853, 1991; blue epithelial buds Mitoxantrone Clin Derm 37:468–486, 2019 Olanzapine – blue-gray pigmentation Int J Dermatol 43:778–779, 2004 Perfloxin – blue-black pretibial hyperpigmentation JAAD 37:365– 381, 1997 Phenothiazine Clin Derm 37:468–486, 2019 Propylthiouracil vasculitis – blue necrotic ear lesions; fever, arthralgias, and myalgias JAMADerm 151:551–552, 2015

Quinacrine

Amlodipine – photolichenoid dermatitis – personal observation

Quinidine AD 122:1062–1064, 1986

Antimalarials – blue-gray pigmentation of the face, neck, forearms, lower legs AD 88:419–426, 1963; yellow and blue pigmentation of pretibial areas and hard palate JAAD 39:524–525, 1998

Quinine – exogenous ochronosis from quinine injections JAAD 15:357–361, 1986

Bismuth – blue linear hyperpigmentation of gingival margin, soft palate, lead JAAD 37:489–490, 1997; AD 129:474–476, 1993

Silver – blue-gray pigmentation JAMADerm 150:984–989, 2014

Chloroquine – blue-gray pigmentation of shins Chlorpromazine – blue-gray pigmentation; corneal and lens opacities Cutis 93:247–250, 2014; JAAD 53:S105–107, 2005 Chrysiasis – blue-gray facial pigmentation following Q-switched Nd:YAG laser following systemic gold therapy JAMADerm 151:1021–1022, 2015 Clofazimine in DLE JAAD 17:867–871, 1987 Clomipramine Am J Psychiatry 146:552–553, 1989 Desipramine photopigmentation AD 129:474–476, 1993 Diltiazem – reticulated, blue-gray, photodistributed hyperpigmentation JAAD 46:468–469, 2002; AD 137:179–182, 2001

Retigabine (ezogabine) Clin Derm 37:468–486, 2019 Silver sulfadiazine cream – blue-gray spots (topical argyria) BJD 163:1124–1126, 2010 Sorafenib – blue-gray hyperpigmentation JAAD 77:902–910, 2017 Tetracycline – blue-green pigmentation of the legs following trauma Ped Derm 21:164–166, 2004; blue-gray pigmentation JAMADerm 150:984–989, 2014 Thorazine ochronosis Vandetanib (kinase and growth factor receptor inhibitor) – photosensitivity, xerosis, and blue-gray perifollicular macules JAAD 77:902– 910, 2017; AD 148:1418–1420, 2012; AD 147:364–365, 2011; also blue-gray pigment within scars AD 145:923–925, 2009 Vitamin K injection reaction

Blue Spots

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EXOGENOUS AGENTS

Metal sutures

Accidental tattoos – collier’s stripes Br J Dermatol Syphilol 52:129–130, 1940; silversmith, IVDA

Pencil tip granuloma – graphite, clay, wax, and lacquer; blue papule of distal phalanx NEJM 366:2408, 2012

Amalgam tattoo Clin Derm 37:468–486, 2019 Argyria – blue-gray generalized hyperpigmentation; cutaneous blue pigmentation – silver salts, colloidal silver dietary supplements, nose drops (Argyrol); topical silver sulfadiazine JAAD 76:S66–68, 2017; JAMADerm 149:623–624, 2013; BJD 159:740–741, 2008; NEJM 351:2349–2350, 2004; Cutis 66:373–374, 2000; topical silver nitrate cream JAAD 55:S92–94, 2006; Histopathol 20:73–75, 1992; Adv Dermatol 2:171–183, 1987; BJD 104:19–26, 1981; AD 113:1077–1079, 1977; argyria due to ingestion of colloidal silver proteins Cutis 89:221–224, 2012; blue nails; occupational – blue nevus-like annulus; from silver ring traumatically implanted AD 132:459–464, 1996; blue nevi-like dotted occupational argyria JAAD 27:1015–1016, 1992; localized argyria and chrysiasis from implanted silver and gold tipped acupuncture needles J Drugs Dermatol 9:1019–1020, 2010; Cutis 80:423–426, 2007; JAAD 29:833–837, 1993; AD 122:1550–1552, 1985; exogenous argyria due to silver mining, manufacture of silverware and metal alloys, electroplating solutions, photographic processing, jewelry, surgical and dental procedures, silver earrings, acupuncture needles JAAD 46:222–227, 2002; homebrew silver solution AD 145:1053–1058, 2009; silversmith – blue macules BJD 175:1052–1055, 2016

Picric acid – yellow skin and hair; blue lips and fingernails Cutis 71:441–442, 448, 2003; Pigment Cell Res 15:119–126, 2002; Rook p. 2965, 1998, Sixth Edition Q-switched alexandrite laser-induced chrysiasis – blue-brown pigmentation Clin in Derm 37:468–486, 2019 Skin metallosis – blue-gray pigmentation due to high-speed drill or barrel trimmer when inserting joint prosthesis BJD 157:1074–1076, 2007; BJD 149:653, 2003 Tattoo pigment fanning – blue periorbital hyperpigmentation Cutis 68:53–55, 2001 Textile dyes – staining Clin Derm 37:468–486, 2019; Cutis 66:287–288, 2000

INFECTIONS AND INFESTATIONS AIDS – blue nails without AZT Cutis 57:243–244, 1996; blue fingernails and toenails Int J STD AIDS 10:479–482, 1999 Aspergillus fumigatus – in CTCL; personal observation

Black dermatographism

Brown recluse spider bite – blue-gray halo around bite; cyanotic pale hemorrhagic bulla progresses to eschar; sunken bluish patch JAAD 67:347–354, 2012; Dermatol Clin 15:307–311, 1997

Black and blue dye – oral mucosal hyperpigmentation Clin Derm 37:468–486, 2019

Brucellosis (panniculitis and fasciitis of the legs) Int J Derm Jan 1994

Blue chromhidrosis – ammonium and copper in drinking water in infants Ped Derm 35:448–452, 2018

Filariasis (Dirofilaria immitis) – zoonotic deep cutaneous filariasis Ped Derm 25:230–232, 2008

Blue suede shoes

Gram-negative web space infection

Butyl nitrate inhalation – blue nose AD 135:90–91, 1999

Haemophilus influenzae facial cellulitis of children Ped Derm 21:90–91, 2004

Bismuth poisoning

Carbolic acid dressings – for chronic ulcers JAAD 52:122–124, 2005 Chrysiasis (gold) – Q-switched laser-induced chrysiasis; prior gold therapy JAAD 55:S59–60, 2006; AD 138:1012–1014, 2002 Clothing dye – textile dye staining Cutis 66:287–288, 2000 Cutaneous pili migrans (embedded hair) – resembling cutaneous larva migrans BJD 144:219, 2001; AD 76:254, 1957 Earring-induced localized iron tattoo JAAD 24:788–789, 1991; silver earrings; blue macules of the posterior earlobe Dermatologica 177:189–191, 1988 Ethnobotanical tattoos – oral mucosal pigmentation Clin in Derm 37:468–486, 2019 Exogenous ochronosis – hydroquinone, phenol, resorcinol, picric acid, chloroquine (intramuscular or oral) Clin in Derm 37:447–467, 2019; BJD 93:613–622, 1975 FD&C blue dye no. 1 – blue discoloration of entire cutaneous surface due to enteral feedings tinted with blue dye NEJM 343:1047–1048, 2000 Foreign bodies (gravel, shrapnel) Gardenia fruit (Shishihakuhito) – contains genipin; blue-gray pigmentation; mesenteric phlebosclerosis JAMADerm 156:351–353. 2020

Leprosy Listeria monocytogenes – neonatal purpuric, bluish papules of the trunk and legs, pustular and morbilliform eruptions AD 130:245,248, 1994; red papules with central pustulation in veterinarians Hautarzt 11:201–204, 1960 Lyme borreliosis(Borrelia burgdorferi) – acrodermatitis chronica atrophicans – red to blue nodules or plaques; tissue-paper-like wrinkling; pigmented; poikilodermatous; hands, feet, elbows, knees JAAD 49:363–392, 2003; BJD 121:263–269, 1989; Int J Derm 18:595–601, 1979; lymphocytoma cutis – bluish-red plaque of earlobes in children and nipple or areola in adults JAAD 49:363– 392, 2003; blue-red edema of the extremities BJD 147:375–378, 2002 Measles – Koplik spots (blue-white spots on buccal mucous membrane with red areola) Mucormycosis – gray-violet plaque (in acute lymphocytic leukemia) JAMADerm 153:923–924, 2017 Mycobacterium tuberculosis – miliary tuberculosis; large crops of blue papules, vesicles, pustules, hemorrhagic papules; red nodules; vesicles become necrotic to form ulcers Practitioner 222:390–393, 1979; Am J Med 56:459–505, 1974; AD 99:64–69, 1969 Necrotizing fasciitis Clin in Derm 37:468–486, 2019

India ink tattoo – oral pigmentation Clin Derm 37:468–486, 2019

Pediculosis pubis – maculae cerulae Int J Dermatol 25:383–384, 1986

Ink – artificial dye Clin Derm 37:468–486, 2019

Pinta – slate blue hyperpigmentation AD 135:685–688, 1999

Mercury-containing bleaching agents – blue-gray pigmentation Cutis 61:248, 1998

Pneumocystis carinii (macule) AD 127:1699–1701, 1991

Hyaluronic acid gel Clin Derm 37:468–486, 2019

Pubic lice – maculae cerulae Clin in Derm 37:468–486, 2019

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Rubella, congenital – blueberry muffin baby Sea urchin spines – initial edema; delayed onset of bluish papules and nodules (granulomas); fusiform swelling of digits Clin Exp Dermatol 2:405–407, 1977 Seal finger Sepsis, neonatal – extramedullary hematopoiesis

Neoplastic infiltrates  Congenital leukemia, including biphenotypic congenital leukemia (acute myelogenous leukemia and acute lymphocytic leukemia) Ped Derm 24:587–588, 2007  Neuroblastoma  Congenital rhabdomyosarcoma (embryonal) AD 138:689–694, 2002

Tick – personal observation

Other disorders  Langerhans cell histiocytosis JAAD 53:S143–146, 2005; Ann DV 119:111–117, 1992   Neonatal lupus erythematosus

TORCH syndrome – extramedullary hematopoiesis, blueberry muffin baby – widespread blue, purple, or red macules, papules, or nodules of the trunk, head, and neck; may develop petechiae on surface; toxoplasmosis, rubella, CMV, Coxsackie B2, herpes simplex, syphilis

Cryoglobulinemia – personal observation

Sporotrichosis (blue nodules) Syphilis – macular syphilid

Carcinoid syndrome – flushing, patchy cyanosis (blue nose), hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea Acta DV (Stockh) 41:264–276, 1961; AD 77:86–90, 1958 Cyanosis JAAD 53:S105–107, 2005

INFILTRATIVE DISEASES Alpha-mannosidosis – dermal melanocytosis AD 139:916–920, 2003 Amyloid, primary systemic – bluish hue to skin of the palms, knees, nares JAAD 77:1145–1158, 2017 Congenital self-healing histiocytosis (Hashimoto-Pritzker disease) – congenital crusted red or blue nodules Skin and Allergy News, Feb 2001, p. 31 GM1 gangliosidosis – dermal melanocytosis AD 139:916–920, 2003 Langerhans cell histiocytosis; urticating Langerhans cell histiocytosis (Hashimoto-Pritzker disease) – red-blue papules Ped Derm 18:41–44, 2001; JAAD 14:867–873, 1986; blueberry muffin baby JAAD 53:S143–146, 2005 Urticaria pigmentosa Hunter’s disease – dermal melanocytosis AD 139:916–920, 2003 Niemann-Pick disease – dermal melanocytosis AD 139:916–920, 2003

INFLAMMATORY DISEASES Neutrophilic eccrine hidradenitis Post-inflammatory hyperpigmentation Subcutaneous fat necrosis – blue plaques BJD 150:357–363, 2004

METABOLIC DISEASES Addison’s disease – slate-like hyperpigmentation JAMADerm 150:984–989, 2014; JAAD 53:S105–107, 2005 Alpha-mannosidase – extensive Mongolian spots Clin Genet 81:379–383, 2012 Dermal erythropoiesis (extramedullary hematopoiesis) – widespread blue, purple, or red macules, papules, or nodules of the trunk, head, and neck; may develop petechiae on surface; JAAD 20:1104–1110, 1989  Congenital infections   Herpes simplex JAAD 53:S143–146, 2005   Rubella   Coxsackie B2   Cytomegalovirus   Syphilis   Toxoplasmosis   Hereditary spherocytosis   Rh incompatibility   ABO blood group incompatibility   Twin-twin transfusion syndrome Pediatrics 74:527–529, 1984

Disseminated intravascular coagulation – personal observation Endometriosis – umbilical blue cutaneous nodule Clin in Derm 37:468–486, 2019; duVivier p. 686, 2003; firm blue nodules of the vulva J Cutan Pathol 13:89, 1986; Obstetrics 40:28–34, 1972 Gangliosidosis type 1 – extensive Mongolian spots JAMADerm 151:1249–1250, 2015; J Pediatr 162:1070, 2013; Indian J Dermatol 56:98–100, 2011; Ped Derm 24:98–99, 2007; Pediatr Neurol 34:143–145, 2006; AD 139:916–920, 2003; Am J Med Genet 87:276–277, 1999; JR Soc Med 86:120–121, 1993; JAAD 20:878– 882, 1989; BJD 104:195–200, 1981; GM1 gangliosidosis type 1 – angiokeratoma corporis diffusum Clin Genet 36:59–64, 1989 Hemochromatosis JAAD 53:S105–107, 2005 Lysosomal storage disease – anterior and posterior dermal melanocytosis in Hurler’s disease, GM, gangliosidosis type 1, Niemann–Pick disease, Hunter’s disease, alpha-mannosidosis AD 139:916–920, 2003 Methemoglobinemia – chloroquine, dapsone, indoxacarb, nail polish remover Clin Derm 37:468–486, 2019; JAAD 53:S105–107, 2005 Myelofibrosis – extramedullary hematopoiesis Nutritional deficiency, chronic Ochronosis (alkaptonuria) – homogentisic acid dioxygenase deficiency; autosomal recessive; blue-black earwax, urine, blue cartilage of the nose and ear, blue tarsal plates of the eyelids, blue-black patches of sclerae; skin of axillae, around areolae, ends of the fingers, cheeks, scleral deposits; blue pigmentation overlying extensor tendons of knuckles JAMADerm 152:465–466, 2016; J Clin Pathol 66:367–373, 2013; JAAD 52:122–124, 2005; NEJM 347:2111–2121, 2002; Biochim Biophys Acta 177:94–105, 1969; Am J Med 34:813–838, 1963; J Biol Chem 230:251–260, 1958 Osteoma cutis – blue papules Cutis 86:100–102, 2010; BJD 146:1075–1080, 2002; osteoma cutis with minocycline AD 134:861–866, 1998; multiple miliary osteoma cutis of the chest AD 141:389–394, 2005 Progressive osseous heteroplasia AD 132:787–791, 1996 Wilson’s disease – generalized blue-gray pigmentation JAMADerm 150:984–989, 2014

NEOPLASTIC Acrospiroma – blue-red nodule Cutis 58:349–351, 1996 Adenoid cystic carcinoma – personal observation; primary cutaneous of the scalp Clin in Derm 37:468–486, 2019 Aggressive digital papillary adenocarcinoma – metastasis presenting as blue papule of the dorsum of the hand JAAD 60:331–339, 2009

Blue Spots Alveolar rhabdomyosarcoma, congenital Angioleiomyoma JAAD Dec 1993; of the tongue Clin in Derm 37:468–486, 2019 Angiolipoleiomyoma – blue nodule JAAD 54:167–171, 2006 Angiolipoma (nodule) AD 126:666–667, 669, 1990; AD 82:924–931, 1960 Angiosarcoma (lymphangiosarcoma) (Stewart-Treves tumor) – ulcerated blue hemorrhagic nodule and plaque in chronic lymphedema AD 146:337–342, 2010; blue nodules in lymphedematous extremity Arch Surg 94:223–230, 1967; Cancer 1:64–81, 1948 Angiosarcoma Cancer 44:1106–1113, 1979; blue plaque JAAD 12:922–926, 1985; resembling arteriovenous malformation JAAD 49:530–531, 2003; angiosarcoma of the breast JAAD 49:532–538, 2003; blue nodules JAAD 50:867–874, 2004 Aneurysmal fibrous histiocytomas (variant of dermatofibroma) BJD 153:664–665, 2005 Apocrine hidrocystoma – blue cystic papule AD 115:194–200, 1979 Basal cell carcinoma – cystic – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 26; pigmented basal cell carcinoma Bednar tumor – congenital dermatofibrosarcoma protuberans; blue–brown nodule of the dorsal foot Ped Derm 28:583–585, 2011 Blue nevi Cutis 80:42–44, 2007; JAAD 49:924–929, 2003; JID 22:225–236, 1954; Bull Assoc Fr Cancer 14:221–249, 1925; common blue nevus with satellitosis mimicking melanoma – multiple blue macules and papules of the scalp AD 145:1183–1188, 2009  Acquired multiple blue nevi BJD 144:440–442, 2001  Agminated Dermatology 186:144–148, 1993; JAAD 4:50–53, 1981  Cellular – blue-gray papules JAAD 71:1241–1249, 2014; Cancer 21:393–405, 1968; Bull Assoc Fr Cancer 14:221–249, 1925  Combination blue nevus and neurocristic hamartoma JAAD 49:924–929, 2003  Combined nevus – blue-black Ped Derm 14:358–360, 1994  Common  Compound  Congenital  Eruptive JAAD 4:50–53, 1981  Familial multiple blue nevi Clin Exp Dermatol 16:308–309, 1991  Large congenital combined nevus – plaque-type blue nevus with a nevus spilus-like background  Malignant JAAD 19:712–722, 1988, Cutis 58:40–42, 1996  Plaque type AD 127:587, 1991  Subungual JAAD 58:1021–1024, 2008; AD 143:937–942, 2007 Carcinoid – primary cutaneous carcinoid of the chest Virchows Arch 408:99–103, 1985; bluish discoloration of the chin, nose, and malar areas JAAD 55:193–208, 2006

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Cylindromas – bluish, pink, red, or skin-colored nodules of the scalp, face, nose, and around ears and neck Cystic hidradenoma Deep penetrating nevus – black, blue, brown, gray, or darkly pigmented nevus of the head, neck, and scalp JAAD 71:1234–1240, 2014 Dermal melanocytic hamartoma AD 117:102–104, 1981 Dermal melanocytosis – blue pigmentation of helix of auricle Ped Derm 27:305–306, 2010; diffuse dermal melanocytosis at birth with development at age 30 of eruptive blue nevi and bilateral nevus of Ota AD 147:1339–1340, 2001; acquired dermal melanocytosis JAAD 73:348–351, 2015; disseminated dermal melanocytosis BJD 101:197–205, 1979 Dermal melanocytosis within an angiosarcoma J Cutan Pathol 16:149–153, 1989 Dermatofibroma (sclerosing hemangioma) Clin in Derm 37:468– 486, 2019 Dermatofibrosarcoma protuberans – congenital blue-black patch, blue plaque, atrophic indurated blue plaque, annular red plaque, pink alopecic plaque, red macule, hypopigmented plaque Ped Derm 25:317–325, 2008; AD 143:203–210, 2007; JAAD 42:907–913, 2000 Digital myxoid cyst – personal observation Eccrine acrospiroma – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 55; giant JAAD 23:663–668, 1990 Eccrine angiomatous hamartoma – vascular nodule; macule, red plaque, acral nodule of infants or neonates; painful, red, purple, blue, blue-red, yellow, brown, skin-colored plaque on extremities, trunk, buttocks, neck Ped Derm 26:316–319, 2009; AD 142:1351– 1356, 2006; Ped Derm 23:365–368, 2006; Ped Derm 23:516–517, 2006; Ped Derm 22:175–176, 2005; JAAD 47:429–435, 2002; JAAD 37:523–549, 1997; Ped Derm 14:401–402, 1997; Ped Derm 13:139–142, 1996; Virchow Arch Pathol Anat 16:160, 1859; skin-colored nodule with blue papules JAAD 41:109–111, 1999 Eccrine hidrocystoma (cystic) AD 124:935–940, 1988; AD 108:676– 679, 1973; blue papules of the nose AD 148:641–646, 2012 Eccrine papillary adenoma – personal observation Eccrine poroma – blue-black pedunculated tumor of the chin BJD 152:1070–1072, 2005 Eccrine spiradenoma – solitary, painful, blue nodule of anterior trunk and proximal extremities Dermatol Surg 26:877–882, 2000; JAAD 2:59–61, 1980 Epidermoid cyst JAAD 52:921–922, 2005

Chordoma, metastatic JAAD 55:S6–10, 2006; AD 141:1595–1600, 2005; Derm Surg 26:259–262, 2000; Cutis 54:250–252, 1994

Eruptive vellus hair cysts AD 131:341–6, 1995; AD 124:1101–1106, 1988; JAAD 3:425–429, 1980; blue-gray discoloration of the face masquerading as nevus of Ota BJD 157:188–189, 2007; AD 113:500–503, 1977

Clear cell hidradenoma Ped Derm 17:235–237, 2000; Cancer 23:641–657, 1969

Extraosseous Ewing’s sarcoma – red-blue congenital sacral mass Soc Ped Derm Annual Meeting, July 2005

Congenital hamartoma of the eccrine sweat gland – blue painless swelling JAAD 47:429–435, 2002

Fibrous histiocytoma

Congenital primitive neuroectodermal tumors Congenital segmental dermal melanocytosis AD 128:521–525, 1992   vs. Acquired bilateral nevus of Ota-like macules   Blue nevus    Mongolian spot    Nevus of Ito    Nevus of Ota

Generalized eruptive histiocytoma – hundreds of skin-colored, brown, blue-red papules; resolve with macular pigmentation; face, trunk, proximal extremities JAAD 20:958–964, 1989; JAAD 17:499–454, 1987; AD 117:216–221, 1981; AD 116:565–567, 1980; Proc R Soc Med 56:1175–1178, 1973; AD 96:11–17, 1967 Glomus tumors (glomangioma), multiple or plaque type J Eur Acad Dermatol Venereol 28:1123–1125, 2014; Photodermtatol Photoimmunol Photomed 29:212–14, 2013; Cutis 83:24–27, 2009; AD 141:1595–1600, 2005; Ped Derm 19:402–408, 2002; hemifacial

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JAAD 45:239–245, 2001; Ped Derm 18:223–226, 2001; AD 127:1717–1722, 1991; Am J Pathol 11:915–936, 1935; subungual or solitary; familial glomangiomas AD 144:1383–1388, 2008; congenital plaquelike glomuvenous malformations – targetoid blue Blaschko-­esque plaques Cutis 84:16–18, 2009 Glomuvenous malformation (plaque-type glomus tumor) (congenital plaque-type glomuvenous malformations) – blue macules, papules, plaques; may be hyperkeratotic; mutation in glomulin gene (GLMN) JAMADerm 152:1379–1380, 2016; Ped Derm 28:528–531, 2011; Ped Derm 26:70–74, 2009; Ped Derm 25:381–382, 2008; JAAD 58:S92–93, 2008; BJD 154:450–452, 2006; Ped Derm 18:223–226, 2001; Am J Human Genet 65:125–133, 1999; Lyon Chir 21:257– 280, 1924; blue-purple nodules with pebbly surface JAAD 56:353– 370, 2007; congenital plaque-type glomuvenous malformation – may resemble capillary malformation (red patch), venous malformation, or blue nevus JAAD 56:353–370, 2007; familial GVM Bull Soc Fr Dermatol Syphiligr 43:736–740, 1936; malignant glomus tumor Am J Surg Pathol 20:233–238, 1996 Granular cell tumor – personal observation Hamartoma of neural origin (blue blebs) JAAD 13:1046–1047, 1985 Hematoma Clin in Derm 37:468–486, 2019 Hidradenoma – blue nodule of interlabial sulcus of the vulva JAAD 75:380–384, 2016 Hidrocystoma – eccrine or apocrine; multiple hidrocystomas Cutis 88:178–181, 2011; eyelid cyst Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, pp. 153–155 Histiocytic lymphoma (reticulum cell sarcoma) – blue-red nodules Am J Dermatopathol 14:511–517, 1992; Cancer 62:1970–1980, 1988 Hybrid cyst – pilomatrixoma and infundibular cyst within a nevus sebaceus (blue-brown papule) Ped Derm 29:213–216, 2012 Kaposi’s sarcoma JAAD 38:143–175, 1998; Dermatology 190:324– 326, 1995; intraoral bluish macule or nodule JAAD 41:860–862, 1999; JAAD 38:143–175, 1998; Dermatology 190:324–326, 1995 Leiomyoma Leiomyosarcoma – blue-black nodule JAAD 48:S51–53, 2003; J Cutan Pathol 15:129–141, 1988; Pathol Eur 9:307–315, 1974; red, brown, yellow, or hypopigmented JAAD 46:477–490, 2002 Leukemia cutis – chloroma – blue-gray plaques of acute or chronic myelogenous leukemia AD 123:251–256, 1987; AD 71:605–614, 1955; congenital monoblastic leukemia JAAD 21:347–351, 1989; biphenotypic congenital leukemia (acute myelogenous leukemia and acute lymphocytic leukemia) – blueberry muffin baby Ped Derm 24:587–588, 2007; acute monoblastic leukemia (M5a) – blue-purple congenital perianal nodule Ped Derm 27:651–652, 2010 Lymphoma – cutaneous T-cell lymphoma – blue polka dots Cutis 34:373–374, 1984; nasal lymphoma – blue nose JAAD 38:310–313, 1998; immunocytoma (low-grade B-cell lymphoma) – blue or reddish-brown papules JAAD 44:324–329, 2001; angiotropic large cell lymphoma – blue plaques of the breasts and shoulders JAAD 48:633, 2003; NK/T-cell lymphoma – blue plaque of the thigh Soc Ped Derm Annual Meeting, 2005; subcutaneous panniculitis-like T-cell lymphoma (with hemophagocytic syndrome) – blue-red nodules of the extremities and face Ped Derm 23:537–540, 2006; Am J Surg Pathol 15:17–27, 1991; intravascular lymphoma – painful gray–brown, red, blue-livid patches, plaques, nodules, with telangiectasia and underlying induration; 40% of patients with intravascular lymphoma present with cutaneous lesions BJD 157:16–25, 2007; primary cutaneous diffuse large B-cell lymphoma, leg type; Bcl-2 expression – red to bluish nodules of one or both legs and ankles JAAD 69:329–340, 2013; JAAD 66:650–654, 2012;

BJD 160:713–716, 2009; AD 143:1520–1526, 2007; AD 143:1144– 1150, 2007 Malignant deep sclerosing blue nevus – blue plaque BJD 151:508– 511, 2004 Malignant fibrous histiocytoma (multilobulated nodule) Medallion-like dermal dendrocyte hamartoma – blue-brown oval depression of the back of neonate; thin hair on surface AD 142:921–926, 2006 Melanocytic nevus, congenital; traumatized, combined compound and blue nevus; congenital nevus – red, white, and blue plaque on flank of newborn mimicking a vascular tumor Ped Derm 30:749– 750, 2013 Melanoacanthoma – blue-gray, brown-gray annular plaque JAMADerm 151:1129–1130, 2015 Pigmented epithelioid melanocytoma – blue-black papule BJD 174:1115–1117, 2016 Melanoma – primary JAAD 20:261–266, 1989; thin nodular AD 146:311–318, 2010; metastatic melanoma BJD 168:428–430, 2013; metastatic melanoma – diffuse melanosis JAAD 50:293–298, 2004; JAAD 35:295–297, 1996; metastatic melanoma – diffuse blue-gray hyperpigmentation JAAD 68:482–486, 2013; primary dermal melanoma AD 140:121–126, 2004; blue scalp nodule AD 144:49– 56, 2008; dermal melanosis Arch Dermatol Syphiligr 28:395–403, 1972; slate blue Dermatology 197:338–342, 1998; JAAD 35:295– 297, 1996; primary or metastatic melanoma mimicking blue nevi Am J Surg Pathol 23:276–282, 1999; generalized melanosis of the leg in metastatic melanoma – multiple blue spots Cutis 93:145–150, 20014; generalized melanosis due to melanoma in acne scars AD 134:861–866, 1998; JAAD 20:261–266, 1989; lentigo maligna; lentigo maligna melanoma; primary dermal melanoma – pedunculated pink papule, dark macule, blue pigmented nevus, domeshaped hemorrhagic papule, changing pigmented nevus JAAD 71:1083–1091, 2014; animal-type melanoma JAAD 73:1031–1039, 2015; tumoral melanosis JAMADerm 150:767–768, 2014 Melanotic neuroectodermal tumor of infancy (odontoameloblastoma) – pigmented oral mass of early infancy Can J Plast Surg 16:41–44, 2008; J Oral Maxillogac Surg 65:1595–1599, 2007; Acta Pathol Jpn 39:465–468, 1989; Cancer 22:151–161, 1968; Beitr Pathol Anat 82:165–169, 1918; gingival and maxillary mass in 7-month-old AD 146:337–342, 2010  Differential diagnosis of rapidly growing mass of anterior maxilla in an infant: AD 146:337–342, 2010   Congenital epulis   Ewing’s sarcoma   Lymphoma   Melanoma    Melanotic neuroectodermal tumor   Metastatic retinoblastoma   Neuroblastoma   Rhabdomyosarcoma   Teratoma Malignant blue nevus with a blue nevus – blue-black plaque with nodule Ped Derm 29:651–655, 2012 Merkel cell carcinoma – reddish-blue nodules; legs, lip, eyelid, scalp, nose JAAD 58:375–381, 2008; Histopathology 7:229–249, 1983 Metaplastic synovial cyst – blue-gray periumbilical nodule near surgical scar AD 142:775–780, 2006 Metastasis – renal cell carcinoma – red-blue scalp nodule Cutis 99:14,25–26, 2017 Mucinous carcinoma of skin – blue-gray nodule SkinMed 11:254– 255, 2013; JAAD 36:323–326, 1997; of the eyelid JAAD 49:941– 943, 2003

Blue Spots Mucocele – intraoral blue cyst AD 101:673–678, 1970 Multiple pigmented terminal hair cysts JAAD 23:1183, 1990

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Spiradenocarcinoma – dark-blue nodule of the chest Ped Derm 32:122–127, 2015

Nerve sheath myxoma – blue-black Am J Dermatopathol 21:55–62, 1999

Spitz nevus Cutis 58:35–39, 1996

Neurilemmoma

Stewart-Treves angiosarcoma – reddish-blue macules and/or nodules which become polypoid; pachydermatous changes, blue nodules, telangiectasias, palpable subcutaneous mass, ulcer JAAD 67:1342–1348, 2012

Neuroblastoma, cutaneous metastases – blanching blue or blue-gray papules or nodules in infant – become white when stroked; most common tumor of infancy Ped Derm 26:473–474, 2009; AD 145:77–82, 2009; Curr Prob Derm 14:41–70, 2002; AD 133:775–780, 1997; JAAD 30:243–249, 1994; JAAD 26:620–628, 1992; JAAD 24:1025–1027, 1991 Neurocristic hamartoma – verrucous blue plaque of the scalp JAAD 49:924–929, 2003; pilar neurocristic hamartoma AD 118:592–596, 1982

Steatocystoma multiplex JAAD 43:396–399, 2000

Trichoepitheliomas (Brooke’s tumor) – multiple – cheeks, eyelids, nasolabial folds; upper trunk and arms; yellow to pink, bluish, telangiectasias on surface AD 126:953,956, 1990; J Cutan Pathol 13:111–117, 1986

Neurothekeoma cellular – mimics melanocytic nevi Am J Surg Pathol 14:113–120, 1990

PHOTODERMATOSES

Nevus of Ito (nevus fuscoceruleus acromio-deltoideus) Tohoku J Exp Med 60:10–20, 1954; J Exp Med 60:10, 1939

Lichen planus actinicus – blue-gray Cutis 72:377–381, 2003

Nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris) JAAD 47:S257–259, 2002; Clin Dermatol 7:11–27, 1989; AD 85:195–208, 1962; BJD 67:317–319, 1955; Jpn J Dermatol 46:369–374, 1939

Riehl’s melanosis

Nevus of Ota-like macules (acquired bilateral nevus of Ota-like macules) (acquired symmetrical dermal melanocytosis) (Hori’s nevus) BJD 152:903–908, 2005; JAAD 48:584–591, 2003; JAAD 10:961–964, 1984

Chronic sun damage – blue nose; personal observation Melasma

PRIMARY CUTANEOUS DISEASES Acne rosacea

Phylloides tumor of the breast Clin in Derm 37:468–486, 2019

Acne vulgaris – open comedones; inflamed acne cyst with hemorrhage

Pigment-synthesizing melanocytic neoplasm with protein kinase C alpha (PRKCA) fusion – ATPase calcium transporting plasma membrane 4 (ATp2B4)-protein kinase C-alpha (PRKCA) fusion transcript JAMADerm 152:318–322, 2016

Acquired bilateral nevus of Ota-like macules (Hori’s nevus) – bluebrown or slate-gray macules, speckled or confluent JAAD 61:88–93, 2009; BJD 154:50–53, 2006; BJD 117:545–553, 1987; JAAD 10:961–964, 1984

Pigmented epithelioid melanocytoma – dark-blue dome-shaped papule Am J Surg Pathol 28:31–40, 2004; Am J Surg Pathol 28:1114–1115. 2004

Acquired dermal melanocytosis (acquired dermal melanocytic hamartoma) – blue-black JAAD 73:348–350, 2015; Int J Dermatol 47:307–308, 2008; J Dermatol 34:178–182, 2007; JAAD 45:609– 613, 2001

Pigmented epithelioid melanocytoma JAAD 77:328–332, 2017 Pigmented spindle cell nevus of Reed JAAD 28:565–571, 1993 Pilomatrixoma – papule; activating mutations in beta-catenin gene Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 71; Rook p. 1700, 1998, Sixth Edition; Pediatr Rev 11(9):262–267, 1990; Cancer 45:2368– 2373, 1980; AD 83:606–618, 1961; Prog Med 8:826, 1880; association with myotonic dystrophy Curschmann-Steinert, Gardner’s syndrome, Rubinstein-Taybi syndrome, and gliomatosis cerebri Ped Derm 26:75–78, 2009   Multiple pilomatrixomas Ped Derm 35:513–514, 548–551, 2018    Constitutional mismatch RPAR deficiency   Rubinstein-Taybi syndrome   Kabuki syndrome    Steinert myotonic dystrophy    Turner’s syndrome   Gardner’s syndrome    Trisomy 9 Plasmacytoma – extramedullary plasmacytoma – blue nodule JAAD 19:879–890, 1988; AD 127:69–74, 1991 Poroid hidradenoma – painful deep red, blue, brown, or violaceous nodule of the arm, scalp, face, or trunk Ped Derm 28:60–61, 2011; AD 146:557–562, 2010 Ranula – intraoral blue lesion Salivary duct cyst – intraoral blue lesion Seborrheic keratosis Clin in Derm 37:468–486, 2019 Smooth muscle hamartoma – bluish-brown pigmentation J Derm Surg 11:714–717, 1985

Acrodermatitis chronica atrophicans – bluish-red edema of the extremities BJD 147:375–378, 2002 Anetoderma, primary AD 120:1032–1039, 1984 Apocrine chromhidrosis (blue dots) JAAD 21:418–420, 1989 Atrophoderma of Pasini and Pierini JAAD 30:441–446, 1994 Chromhidrosis – personal observation Cutis laxa, type 2 – blue sclerae Ped Derm 24:349, 2007 Erythema dyschromicum perstans (ashy dermatosis) – blue-gray patches Int J Dermatol 46:1267–1270, 2007; Cutis 68:25–28, 2001; AD 124:1258–1260, 1988 Giant comedone Granuloma faciale Granuloma multiforme Int J Derm Jan 1994 Idiopathic eruptive macular pigmentation JID Nov. 94 Vol 103 Lichen planus – active in dark-skinned patients; resolving; linear; psoriasiform, lichenoid dermatitis – personal observation Lichen sclerosus et atrophicus – bluish-white plaques of the mouth Macular amyloid Pacinian corpuscle hyperplasia with foreign body giant cell reaction – painful blue macule on palmar thumb JAMADerm 149:97–102, 2013 Pigmented pityriasis alba Ped Derm 10:1–5, 1993 Pityriasis rosea

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Prurigo pigmentosa – flexural reticulated blue-gray pigmentation JAMADerm 155:377–378, 2019 Pseudomyxoma peritonei – blue translucent umbilical lesion AD 96:462–463, 1967 Psoriasis in black patients Striae distensae (striae atrophicans) Terra firme – personal observation Vitiligo – blue vitiligo JAAD 30:829–833, 1994

PSYCHOCUTANEOUS DISEASES

severe early periodontitis with loss of adult dentition by the end of the third decade; cigarette paper scars of shin; marfanoid habitus (tall, long limbs, arachnodactyly); triangular face, prominent eyes, thin nose, prematurely aged appearance, thin skin with prominent veins, no joint hypermobility, easy bruising, blue sclerae JAAD 55:S41–45, 2006; Heritable Disorders of Connective Tissue, 4th Ed, St. Louis: Mosby 1972 Fabry’s disease – angiokeratoma corporis diffusum BJD 166:712– 720, 2012 Familial chilblain lupus erythematosus – acral cyanotic papules; mutation in TREX1 BJD 166:212–214, 2012 Franceschetti-Jadassohn syndrome

Factitial injection of blue ink – blue forearm AD 143937–942, 2007

Goltz’s syndrome – blue sclerae

Factitial purpura

Hallermann-Streiff syndrome – blue sclerae J Pediatr 93:892–893, 1978

SYNDROMES Albright’s hereditary osteodystrophy (pseudohypoparathyroidism) – osteoma cutis; blue–tinged stony–hard papules Antiphospholipid antibody syndrome – blue fingers and toes Semin Arthritis Rheum 31:127–132, 2001; JAAD 36:149–168, 1997; JAAD 36:970–982, 1997; BJD 120:419–429, 1989 Atrichia with papular lesions – blue cystic papules of the face, scalp, neck JID 118:887–890, 2002; JID 117:612–617, 2001 Blue rubber bleb nevus syndrome (Bean syndrome) – autosomal dominant, sporadic; blue lesions of skin and mucous membranes; venous malformations; localized hyperhidrosis; venous malformations of small intestine and colon; also central nervous system, orbit, genitourinary tract BJD 166:1143–1145, 2012; Ped Derm 29:524– 525, 2012; JAAD 65:893–906, 2011; JAAD 56:541–564, 2007; JAAD 50:S101–106, 2004; Ped Derm 16:222–227, 1999; Cutis 62:97–98, 1998; Trans Pathol Soc 11:267, 1860 Caplan syndrome – blue sclerae Clin Derm 37:468–486, 2019 Carney complex (NAME/LAMB) – epithelioid blue nevi JAAD 61:80–87, 2009; Medicine (Baltimore) 64:270–283, 1985; JAAD 46:161–183, 2002; Br Heart J 35:874–876, 1973; acromegaly, facial lentigines, cutaneous myxoma, blue nevus of the vulva; gain-offunction mutation of PRKACB (catalytic subunit alpha of cAMPdependent protein kinase) NEJM 370:1065–1067, 2014 Cerebral cavernous malformations (cutaneous hyperkeratotic capillary-­venous malformation associated with familial cerebral cavernous malformations) (familial cerebral cavernomas) type 1 – autosomal dominant; localized dark red hyperkeratotic plaques; violaceous to blue-black plaques (malformations); red blanchable patches; red hyperkeratotic plaques; deep blue nodules; cutaneous venous malformations; mutations in CCM-1 gene which encodes for Krev-1 interaction TRAP 1 protein (KRIT1) Cutis 96:329–332, 2015; Ped Derm 26:666–667, 2009; JAAD 56:541–564, 2007; BJD 157:210–212, 2007; Hum Molec Genet 9:1351–1355, 2000; Ann Neurol 45:250–254, 1999; Lancet 352:1892–1897, 1998; CCM2 – malcaverin protein; CCM3 – PDCD10 protein Cornelia de Lange syndrome – specific facies, skin around eyes and nose with bluish tinge, hypertrichosis of the forehead, face, back, shoulders, and extremities, synophrys; long delicate eyelashes, cutis marmorata Ehlers-Danlos syndrome – blue sclerae; blue-gray molluscoid pseudotumors (hematomas) over pressure points, pretibially, and on forearms JAAD 46:161–183, 2002; Rook pp. 2032–2038, 1998, Sixth Edition; type VI – blue sclerae, scleral fragility, joint hypermobility, skin hyperextensibility, easy bruising, atrophic scarring, marfanoid habitus, scoliosis, neonatal hypotonia, arterial dissection; type VIII – autosomal dominant; skin fragility, abnormal scarring,

Hemimaxillofacial dysplasia (segmental odontomaxillary dysplasia) (HATS – hemimaxillary enlargement, asymmetry of the face, tooth findings, skin findings)– facial asymmetry, hypertrichosis of the face, unilateral maxillary enlargement, partial anodontia, delayed eruption of teeth, gingival thickening of the affected segment, Becker’s nevus, hairy nevus (hypertrichosis), lip hypopigmentation, depression of the cheek, erythema, hypoplastic teeth Ped Derm 21:448– 451, 2004; JAAD 48:161–179, 2003; Oral Surg Oral Med Oral Pathol 64:445–448, 1987 Hereditary acrolabial telangiectasia – blue lips, areolae, blue lunulae and nail beds, telangiectasias on hands, chest, and elbows, dorsa of the hands, varicosities of the legs, migraine headaches AD 115:474–478, 1979 Hunter’s syndrome – extensive (extrasacral) Mongolian spots Ped Derm 33:594–601, 2016; Clin Genet 81:379–383, 2012; AD 139:916–920, 2003; BJD 148:1173–1178, 2003; AD 134:108–109, 1998; JAAD 39:1013–1015, 1998; Am J Med Genet 47:456–457, 1993 Hurler’s syndrome – extensive Mongolian spots Ped Derm 33:594–601, 2016; J Eur Acad Dermatol Venereol 21:1082–1085, 2007; BJD 148:1173–1178, 2003; AD 139:916–920, 2003; Ann DV 126:35–37, 1999; AD 134:108–109, 1998; JAAD 39:1013–1015, 1998 Hurler-Scheie syndrome – extensive Mongolian spots Clin Genet 81:379–383, 2012 Hutchinson-Gilford syndrome – midfacial cyanosis Incontinentia pigmenti – blue-gray hyperpigmentation of third stage; blue sclerae; atrophic stage Ped Derm 15:108–111, 1998; Curr Prob in Derm VII:143–198, 1995; AD 112:535–542, 1976 Kabuki makeup syndrome – short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high-arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low-set ears with thick helix), low-cut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly; preauricular dimple/fistula Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170– 173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849– 850, 1984; J Pediatr 99:565–569, 570–573, 1981 Loeys-Dietz syndrome – joint hypermobility, thin skin with prominent veins, marfanoid body habitus, triangular delicate face, hypertelorism, bifid uvula or cleft palate, arterial dissection and rupture,

Blue Spots

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prominent eyes, blue sclerae, aortic aneurysms, generalized arterial tortuosity; type I and II TGF beta receptor JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005

Russell-Silver syndrome – blue sclerae; café au lait macules, short immature bones, triangular facies JAAD 40:877–890, 1999; J Med Genet 36:837–842, 1999

Maffucci’s syndrome (enchondromatosis) – enchondromas and multiple venous malformations; spindle cell hemangioendothelioma; oral and intra-abdominal venous and lymphatic anomalies; blue papule or nodule; short stature, shortened long bones with pathologic fractures; enchondromas undergo sarcomatous change in 30–40%; breast, ovarian, pancreatic, parathyroid, pituitary tumors AD 142:641–646, 2008; Cutis 79:115–117, 2007; JAAD 56:541– 564, 2007; AD 142:641–646, 2006; AD 138:259–264, 2002; AD 138:259–264, 2002; JAAD 42:275–279, 2000; Ped Derm 17:270– 276, 2000; JAAD 37:887–920, 1997; Ped Derm 12:55–58, 1995

Segmental neurofibromatosis – blue-red pseudoatrophic plaques Cutis 94:149–152, 2014 Spondyloepimetaphyseal dysplasia with joint laxity – blue sclerae Skel Radiol 5:205–212, 1980 Turner’s syndrome – blue sclerae JAAD 36:1002–1004, 1996

TOXINS Lead JAAD 37:489–490, 1987

Marfan syndrome – blue sclerae; long extremities, arachnodactyly, skeletal, ocular, cardiovascular defects; Int J Derm 28:291–299, 1989

TRAUMA

Marshall-Smith syndrome J Med Genet 17:174–178, 1980

Chilblains

Morquio’s syndrome (mucopolysaccharidosis type IV) – blue-gray teeth due to enamel hypoplasia Atlas of Clinical Syndromes: A Visual Aid to Diagnosis, 1992, pp. 124–125

Child abuse mimicking soft tissue sarcoma – blue subcutaneous tumor of the shoulder Ped Derm 31:708–711, 2014

Neurofibromatosis type I – blue-red macules JAAD 61:1–14, 2009; Ann DV 129:180–181, 2002; AD 118: 577–581, 1982; subungual glomus tumors JAAD 32:277–278, 1995; multiple glomus tumors JAAD 71:44–48, 2014; J Med Genet 39:e45, 2002; J Dermatol 26:418–419, 1999; JAAD 32:277–278, 1995

Radiation – postradiation angiosarcoma; radiation tattoo Clin Derm 37:468–486, 2019

Niemann-Pick disease – Mongolian spots of skin and oral mucosa AD 139:916–920, 2003

Road rash tattoo Clin Derm 37:468–486, 2019

Osteogenesis imperfecta (Cole-Carpenter syndrome) – blue sclerae; thin fragile skin NEJM 371:465–472, 2014; Am J Med Genet 31:1470–1481, 2014; Eur J Med Genet 51:383–408, 2008; J Pediatr 110:76–80, 1987; Trans Ophthalmol Soc UK 104:191–195, 1985; J Med Genet 16:101–116, 1979; blue teeth JAAD 46:161– 183, 2002; mutation in WNT1 NEJM 368:1809–1816, 2013

Traumatic tattoos

Phakomatosis pigmentokeratotica – speckled lentiginous nevus in association with nevus sebaceus Dermatology 197:377–380, 1998 Phakomatosis pigmentovascularis – cutis marmorata telangiectatica congenita and Mongolian spots JAAD 66:341–342, 2012; port-wine stain, oculocutaneous (dermal and scleral) melanosis, CNS manifestations; type I – PWS and linear epidermal nevus; type II – PWS and dermal melanocytosis Ped Derm 27:303–304, 2010; type IIb – nevus flammeus and aberrant Mongolian spots AD 129:340– 342, 1993; type III – PWS and nevus spilus; type IV – PWS, dermal melanocytosis, and nevus spilus; types II, III, and IV may also have nevus anemicus Ped Derm 21:642–645, 2004; J Dermatol 26:834– 836, 1999; Ped Derm 15:321–323, 1998; Ped Derm 13:33–35, 1996; AD 121:651–653, 1985; Jpn J Dermatol 52:1–3, 1947; type V – extensive Mongolian spot, nevus flammeus, cutis marmorata telangiectatica Ped Derm 25:198–200, 2008; BJD 156:1068–1071, 2007; phakomatosis cesioflammea – Mongolian spots or dermal melanocytosis with one or more port-wine stains AD 141:385–388, 2005; phakomatosis cesiomarmorata – Mongolian spot and cutis marmorata telangiectatica congenita AD 141:385–388, 2005 POEMS syndrome – cutaneous angiomas, blue dermal papules associated with Castleman’s disease (benign reactive angioendotheliomatosis), diffuse hyperpigmentation, morphea-like changes, maculopapular brown-violaceous lesions, purple nodules JAAD 44:324–329, 2001; JAAD 40:808–812, 1999; Cutis 61:329–334, 1998; JAAD 21:1061–1068, 1989; AD 124:695–698, 1988; JAAD 12:961–964, 1985 Pseudoxanthoma elasticum – blue sclerae AD 124:1559, 1988; JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999 Roberts-pseudothalidomide syndrome – blue sclerae Hum Genet 61:372–374, 1982

IVDA – skin popping; intravenous drugs

Rectus sheath hematoma of the abdomen Ritualistic behavior (cupping) Subungual hematoma

VASCULAR Acquired phlebectasia of the glans penis JAAD 13:824–826, 1985 Acquired progressive lymphangioma JAAD 24:813–815, 1991 Acral arteriovenous hemangioma Dermatologica 113:129–141, 1956 Acroangiodermatitis – resembles Kaposi’s sarcoma BJD 120:575– 580, 1989; acroangiodermatitis of the amputation stump BJD 131:915–917, 1994 Acrocyanosis – blue hands, nails, feet, nose, ears, lips, nipples JAAD S207–208, 2001 Acute hemorrhagic edema of infancy – Seidlmayer’s syndrome Aneurysmal dilatation of the internal jugular vein – soft blue neck mass Ped Clin North Amer 6:1151–1160, 1993 Angiokeratoma circumscriptum AD 117:138–139, 1981 Angiokeratoma of Mibelli – autosomal dominant; associated with chilblains; on the dorsum of the fingers, toes, hands, feet AD 106:726–728, 1972 Angiokeratoma, solitary papular – occur after trauma in adult life – red to blue-black BJD 157:210–212, 2007; may rapidly enlarge or bleed and simulate melanoma AD 117:138–139, 1981; AD 95:166–175, 1967; acral angiokeratomas of Mibelli in Turner’s syndrome – blue-black keratotic vascular papules Ped Derm 27:662–664, 2010 Arteriovenous fistula (traumatic) – of the lip Cutis 62:235–237, 1998 Arteriovenous malformation – faint blue macule of the scalp JAAD 46:934–941, 2002; giant arteriovenous malformation with mountain range appearance AD 143:1043–1045, 2007 Bockenheimer’s syndrome (genuine diffuse phlebectasia) – extensive venous malformation; diffuse phlebectasia; blue network of dilated veins JAAD 56:541–564, 2007; Ped Derm 23:294–297, 2006

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Buerger’s disease Capillary-venous malformation with phlebectasia of the lower limb – hemihypertrophy with small well-defined blotchy blue patches amid prominent leg veins; prominent veins of the popliteal fossa, knee, and dorsal foot Ped Derm 30:541–548, 2013 Cerebral cavernous malformations (cutaneous hyperkeratotic capillary-­venous malformation associated with familial cerebral cavernous malformations) (familial cerebral cavernomas) type 1 – autosomal dominant; localized dark red hyperkeratotic plaques; violaceous to blue-black plaques (malformations); red blanchable patches; red hyperkeratotic plaques; deep blue nodules; cutaneous venous malformations; mutations in CCM-1 gene which encodes for Krev-1 interaction TRAP 1 protein (KRIT1) Ped Derm 26:666–667, 2009; JAAD 56:541–564, 2007; BJD 157:210–212, 2007; Hum Molec Genet 9:1351–1355, 2000; Ann Neurol 45:250–254, 1999; Lancet 352:1892– 1897, 1998; CCM2 – malcaverin protein; CCM3 – PDCD10 protein

396, 2010; JAAD 54:S214–217, 2006; Pediatrics 117:e810–813, 2006; AD 140:599–606, 2004; multifocal lymphangioendotheliomatosis without thrombocytopenia or gastrointestinal bleeding Ped Derm 36:965–966, 2019 Multiple progressive angioma – blue compressible nodules on the face of children or teenagers; may be distributed along the vein Acta DV (Stockh) 31:304–307, 1951 Non-involuting congenital hemangioma (NICH) – red patch; blue patch; red nodules; blue plaque with central telangiectasia and peripheral rim of pallor Ped Derm 36:835–853, 2019; Ped Derm 32:710–713, 2015; JAAD 70:899–903, 2014; blue nodules BJD 171:466–473, 2014 Pernio, chronic – blue toes Int Angiol 11:46–50, 1992

Cherry angioma

Phlegmasia cerulea dolens – massive proximal venous thrombosis resulting in arterial insufficiency; triad of asymmetric leg edema, hemorrhagic bullae, cyanosis, blue feet, acral necrosis, pain NEJM 370:1742–1748, 2014

Cholesterol emboli – blue toes JAAD 55:786–793, 2006

Pigmented purpuric eruption

Cirsoid aneurysm (arteriovenous fistula) – blue non-pulsatile nodules of nail fold BJD 115:361–366, 1986; digital arteriovenous malformation – subungual blue papule BJD 147:1007–1011, 2002; BJD 136:472–473, 1997

Polyangiitis with granulomatosis – blue gingival hypertrophy

Coagulopathy Cobb’s syndrome Congenital nonprogressive hemangiomas – blue nodules AD 137:1607–1620, 2001 Congenital plaque-type glomuvenous malformations – glomulin gene on 1p21; loss of function mutation; atrophic at birth; livedoid plaques, blue plaques, vascular nodules, red patches, cerebriform, targetoid AD 142:892–896, 2006 Cutaneous polyarteritis nodosa – plaque JAAD 13:661–663, 1985 Cutaneomucosal venous malformation – skin, mucosa, and joints; painful on awakening and after activity; not painful on palpation; difficult to distinguish from glomuvenous malformation; TIE2/TEK, 9p2 gain-of-function mutation Ped Derm 26:7074, 2009 Cutis marmorata telangiectatica congenita Ecchymoses (normal bruising) Familial cerebral cavernous malformation – blue papules JAMADerm 149:97–102 Granulomatosis with polyangiitis – personal observation Hemangioma, Clin in Derm 37:468–486, 2019; blue mass of the breast Ped Derm 37:40–1, 2020; Ped Derm 32:690–695, 2015; especially deep infantile hemangiomas Intravascular papillary endothelial hyperplasia (Masson’s tumor) (pseudoangiosarcoma) – mimics angiosarcoma; red-blue tender nodule Cutis 59:148–150, 1997; AD 114:723–726, 1978; blue-gray firm nodule of the arm within congenital vascular anomaly in newborn Ped Derm 30:745–747, 2013 Kasabach-Merritt syndrome – blue-black tumid mass Ped Derm 34:261–265, 2017

Pseudoaneurysm – pulsatile nodule of the wrist following transradial coronary angiography NEJM 373:1361, 2015 Purpura fulminans (DIC) – peripheral symmetric gangrene with blue nose JAAD 47:493–496, 2002 Purpura simplex Pyogenic granuloma – blue-black papule Rapidly involuting congenital hemangioma – blue nodules BJD 171:466–473, 2014; blue leg BJD 158:1363–1370, 2008; large violaceous gray-blue nodule of the scalp with overlying telangiectasia Soc Ped Derm Annual Meeting, 2005 Reactive hemangioendotheliomatosis – red-blue patch JAAD 42:903–906, 2000 Sinus pericranii – alopecic blue nodule of the scalp JAAD 46:934– 941, 2002 Superficial hemosiderotic lymphovascular malformation (hobnail hemangioma) (targetoid hemosiderotic hemangioma) – red-brown papule; blue-purple papule; yellow/green blue papule Ped Derm 31:281–285, 2014 Telangiectasias Derm Surg 23:55–59, 1997 Thrombosed capillary aneurysm – personal observation Thrombosis of palmar digital vein – painful firm blue nodule Ann Dermatol 24:351–354, 2012 Thrombosed vein Clin Podiatr Med Surg 13:85–89, 1996 Tufted angioma – blue macule Ped Derm 35:808–816, 2018; blue plaque or nodule Ped Derm 19:394–401, 2002; oral red or blue papule BJD 142:794–799, 2000 Varicosities, including thrombosed varix of the eyelid – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999. p. 119

Lymphangiosarcoma of Stewart-Treves

Vascular anomaly (malformation) – syndromes associated with vascular malformations include:    Blue rubber bleb nevus syndrome   Klippel-Trenaunay syndrome   Maffucci’s syndrome   Osler-Weber-Rendu disease   Parkes-Weber syndrome   Proteus syndrome   Sturge-Weber syndrome

Malignant angioendotheliomatosis JAAD 18:407–412, 1988

Vasculitis, including urticarial vasculitis

Multifocal lymphangioendotheliomatosis with thrombocytopenia – blue-red 2–4 mm papules; red-brown macules Ped Derm 27:395–

Venous aneurysm – painful blue nodule of the hand AD 140:1393– 1398, 2004

Kaposiform hemangioendothelioma – red-blue tumid swelling Am J Surg Pathol 17:321–328, 1993; swollen blue finger Cases of the Year, Pre-AAD Pediatric Dermatology Meeting Klippel-Trenaunay-Weber syndrome – blue nails Lymphangioma of alveolar ridges of black infants Pediatrics 56:881, 1976

Blueberry Muffin Lesions, Neonate Venous and mixed venous and lymphatic malformations AD 146:1347–1352, 2010; AD 144:861–867, 2008; JAAD 56:353–370, 2007; AD 139:1409–1416, 2003; JAAD 46:934–941, 2002; JAAD 45:239–245, 2001

METABOLIC DISORDERS

Venous lake AD 74:459–463, 1956

Twin transfusion syndrome Pediatrics 74:527–529, 1984

Venous malformation, multiple cutaneous and mucosal syndrome – TIE2/TEK; no visceral venous malformations JAAD 56:541–564, 2007; venous malformation – discrete mass with soft tissue swelling; may be blue or with skin discoloration Ped Derm 30:534–540, 2013; zosteriform venous malformation Clin in Derm 37:468–486, 2019 Venous stasis ulceration (chronic venous insufficiency) – bluish discoloration precedes ulceration Rook p. 2258, 1998, Sixth Edition Verrucous hemangioma – bluish-red Ped Derm 17:213–217, 2000; keratotic blue plaque BJD 171:466–473, 2014 Congenital Volkmann ischemic contracture (neonatal compartment syndrome) – upper extremity circumferential contracture from wrist to elbow; necrosis, cyanosis, edema, eschar, bullae, purpura; irregular border with central white ischemic tissue with formation of bullae, edema, or spotted bluish color with necrosis, a reticulated eschar or whorled pattern with contracture of the arm; differentiate from necrotizing fasciitis, congenital varicella, neonatal gangrene, aplasia cutis congenital, amniotic band syndrome, subcutaneous fat necrosis, epidermolysis bullosa BJD 150:357–363, 2004 Zosteriform venous malformations Dermatologica 161:347–354, 1980; AD 113:848–849, 1977

 LUEBERRY MUFFIN LESIONS, B NEONATE Ped Derm 28:85–93, 2011; Adv Dermatol 21:153–192, 2005; Semin Dermatol 14:179–186, 1995

AUTOIMMUNE DISEASES Hemophagocytic lymphohistiocytosis (HLH) Ped Derm 34:e150– 151, 2017 Neonatal lupus erythematosus

INFECTIONS AIDS Coxsackie virus B2 JAAD 37:673–705, 1997 Cytomegalovirus, congenital NEJM 362, 833, 2010; AD 126:113, 1988 Herpes simplex Rubella, congenital – Ped 40:627–635, 1967 Sepsis, neonatal Parvovirus B19 JAAD 37:673–705, 1997; J Pediatr 128:579–586, 1996 Syphilis Toxoplasmosis

INFILTRATIVE DISORDERS Langerhans cell histiocytosis JAAD 53:S143–146, 2005; Ped Derm 20:335–338, 2003; Hashimoto-Pritzker disease Dermpath 7:37–40, 2019 Xanthogranulomas – congenital systemic juvenile xanthogranulomatosis Ped Derm 28:606, 2011

153

Transient neonatal myeloproliferative disorder JAAD 54:S22–27, 2006; An Pediatrics (Barc) 61:546–550, 2004

NEOPLASMS Adrenocortical carcinoma Ped Derm 28:85–93, 2011 Alveolar cell rhabdomyosarcoma Acta Paediatr 89:115–117, 2000; J Dermatol 16:409–411, 1989 Choriocarcinoma Ped Derm 28:85–93, 2011 Dermal erythropoiesis and metastatic neuroblastoma, simultaneous in the same lesion JAAD 64:1197–1198, 2011 Leukemia – congenital leukemia – acute myelogenous leukemia AD 145:321–326, 2009; Ped Derm 21:458–461, 2004; JAAD 21:347, 1989; monocytic leukemia AD 132:341–346, 1996; monoblastic leukemia Ann DV 126:157–159, 1999; JAAD 21:347–351, 1989; aleukemic congenital leukemia cutis Ped Derm 21:458–461, 2004 Malignant histiocytosis JAAD 54:S22–27, 2006 Multifocal lymphangioendotheliomatosis Adv Dermatol 21:153–192, 2005 Myofibromatosis Adv Dermatol 21:153–192, 2005 Neuroblastoma metastases to skin J Urol 104:193, 1970; ganglioneuroblastoma J Med Case Rep 11:239, 2017 Primitive neuroectodermal tumor Ped Derm 28:85–93, 2011 Rhabdoid tumor Ped Derm 28:85–93, 2011 Rhabdomyosarcoma (alveolar cell rhabdomyosarcoma), congenital Ped Derm 20:335–338, 2003; J Dermatol 16:409–411, 1989

PRIMARY CUTANEOUS DISEASES Normals JAAD 37:673–705, 1997

SYNDROMES Aicardi-Goutières syndrome (interferonopathy) – autosomal recessive; intracranial calcification with enlarged ventricles; progressive encephalopathy; increased cerebrospinal fluid interferon alpha and lymphocytosis; neurodegenerative disease; mutation in threeprime repair exonuclease 1 (TREX1; AGS1); mutation in sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1; AGS5); mutation in three genes encoding for components of ribonuclease H@ subunit A endonuclease complex (AGS2-4); mutation in gene for RNA-specific adenosine deaminase 1 (AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1 (AGS7); chilblain-like lesions; acrocyanosis; red periungual lesions; red earlobes; livedo reticularis, blueberry muffin baby; congenital encephalopathy with developmental delay; microcephaly; narrow facial features; seizures, spasticity, dystonic posturing Ped Derm 33:602–614, 2016; Ped Derm 26:432–435, 2009 Chromosome 20, genetic anomaly Ann DV 125:199–201, 1998

VASCULAR DISORDERS Blue rubber bleb nevus syndrome Adv Dermatol 21:153–192, 2005 Chronic fetomaternal hemorrhage Diffuse neonatal hemangiomatosis Ped Derm 14:383–386, 1997 Extramedullary hematopoiesis – epsilon gamma delta beta thalassemia Ped Dev Path 22:599–600. 2019

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Glomangiomas Adv Dermatol 21:153–192, 2005 Hemolytic anemia – severe and chronic prenatal anemias; congenital spherocytosis Hemolytic disease of newborn (Rh or ABO incompatibility) J Ped 107:799, 1985 Hereditary spherocytosis Cutis 101:111–114, 2018; AD 117:492, 1981 Intracranial hemorrhage (severe internal bleeding)

BREAST ASYMMETRY CONGENITAL ADULT (acro-dermato-ungual lacrimal tooth syndrome) – limb mammary-like syndrome with ectrodactyly, mammary hypoplasia, excess freckling without facial freckling Hum Mol Genet 11:799– 804, 2002

erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAAD 61:1060–1069, 2009 Supernumerary breasts Aesth Plast Surg 18:399–403, 1994 Tricho-odonto-onycho-ectodermal dysplasia (linear dermal hypoplasia) – hypotrichosis, hypodontia, focal linear dermal hypoplasia of the tip of the nose, irregular hyperpigmentation of the back, bilateral amastia and athelia, nerve hearing loss AD 122: 1047–1053, 1986 Tuberous breast deformity (constricting ring) JAAD 80:1467–1481, 2019 Uneven bilateral hypertrophy Aesth Plast Surg 18:399–403, 1994 Unilateral hypoplasia or hypertrophy Aesth Plast Surg 18:399–403, 1994

ACQUIRED

Aplasia

Abscesses – Staphylococcus aureus, coagulase-negative (Staphylococcus epidermidis) – abscesses of the breast in the neonate; Mycobacterium abscessus mastitis following body piercing Clin Inf Dis 33:131–134, 2001

Asymmetry with ptosis of the breast Aesth Plast Surg 13:47–53, 1989

Becker’s nevus – unilateral breast hypoplasia Clin Exp Derm 22:240–241, 1997; AD 128:992–993, 1992

Becker’s nevus syndrome – unilateral breast hypoplasia accompanying Becker’s nevus JAAD 63:1–22, 2010; Semin Cutan Med Surg 26:221–230, 2007; Am J Med Genet 68:357–361, 1997

Breast carcinoma, including male breast cancer – unilateral gynecomastia Cutis 69:98–102, 2002

Breast hypoplasia – personal observation

Epidermal nevus – personal observation

Byars-Jurkiewicz syndrome – giant fibroadenomas of the breast, secondary kyphosis, hypertrichosis, gingival fibromatosis Plast Reconstr Surg 27:608–612, 1961

Fibroadenomas, giant S Afr J Surg 27:171–172, 1989

Amastia

Congenital asymmetry (idiopathic) Aesth Plast Surg 18:399–403, 1994 Ectrodactyly-ectodermal dysplasia-clefting syndrome – mammary or nipple hypoplasia; kidney or urologic abnormalities Ped Derm 28:15–19, 2011 Finlay-Marks syndrome (scalp-ear-nipple syndrome) – nipple or breast hypoplasia or aplasia, aplasia cutis congenita of the scalp, cleft lip/palate, cardiac malformations, polydactyly, narrow convex nails Hamartoma of the breast Scand J Plast Reconstr Surg Hand Surg 31:365–369, 1997 Hypoplasia associated with hypertrophy Aesth Plast Surg 18:399– 403, 1994

Chest burns Aesth Plast Surg 18:399–403, 1994

Filariasis – chronic edema of the breast with elephantiasis Dermatol Clin 7:313–321, 1989 Finasteride – unilateral gynecomastia AD 138:543–544, 2002 Intralesional steroids Leukemia – acute lymphoblastic leukemia masquerading as gynecomastia Am J Med 108:677–679, 2000 Lupus erythematosus – lupus panniculitis (lupus profundus) – thighs, buttocks, arms, breasts, face AD 122:576, 1986; AD 103:231–242, 1971 Morphea – morphea in hypoplastic breast BJD 93(Suppl 11):44–45, 1975 Neoplasm Aesth Plast Surg 18:399–403, 1994

Incontinentia pigmenti – breast hypoplasia or aplasia JAAD 47:169–187, 2002

Oleomas – multiple subcutaneous oleomas due to injection with sesame seed oil BJD 149:1289–1290, 2003

Infantile hemangioma – blue mass of the breast Ped Derm 37:40–1, 2020

Q fever (Coxiella burnetii) – hypertrophy of the breast Clin Inf Dis 66:793–795, 2018

Limb mammary syndrome – ectrodactyly, mammary gland/nipple hypoplasia, cleft palate Am J Hum Genet 64:481–492, 2001

Radiation therapy in childhood Aesth Plast Surg 18:399–403, 1994

Pigmented hairy epidermal nevus syndrome – unilateral brown hyperpigmented plaques with hypertrichosis; generalized checkerboard pattern, ipsilateral hypoplasia of the breast, skeletal abnormalities JAAD 50:957–961, 2004

Scarring due to infection, surgery, or burns

Poland’s chest wall deformity (Poland syndrome) – breast and pectoralis muscle hypoplasia; ichthyosis, absence of axillary hair, ipsilateral chest wall and upper extremity defects, syndactyly, dermatoglyphic abnormalities JAAD 80:1467–1481, 2019; Plast Reconstr Surg 106:98–101, 2000; Plast Reconstr Surg 99:429–436, 1997; J Bone Joint Surg 58(11):52–58, 1976 Porokeratotic adnexal ostial nevus (cornifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic lesions with comedones; presents as red patch with red and atrophic linear and curvilinear

Resolving hemangioma Silicone collapse – rupture of silicone bag gel implant; red inflamed asymmetric breasts JAAD 64:1–34, 2011 Superpotent topical steroids

 REAST CANCER, CUTANEOUS B MANIFESTATIONS Am J Dermatopathol 34:347–392, 2012 Breast cancer, increased risk JAAD 80:1467–1481, 2019   Ataxia telangiectasia   Cowden’s syndrome

Breast Hypertrophy (Gynecomastia) and Breast Masses                  

Bloom’s syndrome Down’s syndrome Fanconi’s anemia McCune-Albright syndrome Muir-Torre syndrome Nevoid basal cell carcinoma syndrome Peutz-Jeghers syndrome Poland syndrome Scalp-ear-nipple syndrome

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Mimicking pyogenic granuloma G Ital DV 154:95–96, 2019; Cancer Invest 17:385–390, 1999 Mimicking cutaneous vasculitis Cancer 59:1184–1186, 1987 Male breast cancer metastases Med J Malaysia 68:168–170, 2013; JAAD 55:1101–1102, 2006

PARANEOPLASTIC SYNDROMES

Nodular carcinoma – diffuse subcutaneous nodules, no surface change Cutis 101:219–223, 2018; Dermatol Ther 23:581–589, 2010

Dermatomyositis Rheumatol Int 30:1091–1093, 2010; amyopathic JAAD 41:874–875, 1999

Alopecia neoplastica – scalp metastases as initial sign of occult primary breast carcinoma Int J Women’s Dermatol 4:230–235, 2018; AD 84:490–492, 1961

Paraneoplastic pemphigus Oral Oncol 40:553–562, 2004

Telangiectatic carcinoma JAAD 60:633–638, 2009 Malignant melanoma-like metastases Int Wond J 16:1570–1571, 2019; Dermatol Online J 14:12 Nov 15, 2008 Carcinoma erysipelatoides (inflammatory breast cancer) JAMA Oncol 3:1579–1580, 2017 Subungual metastases Dermatol Surg 27:290–293, 2001 Carcinoma en cuirasse Proc (Baylor Univ Med Cent)32:263–265, 2019; Dermatol Surg 30:226–228, 2004; indurated plaques with ulceration Dermatol Online J 02115, 2012 Carcinoma hemorrhagiectoides Dermatol Online J 2017 June 15:23(6):13030/qt3hm3z850 Sclerodermiform metastases An Bras Dermatol 89:360–363, 2014 Umbilical metastases – Sister Mary Joseph nodule J Cutan Pathol 36:702–705, 2009 Widespread generalized cutaneous metastases Clin Case Rep 8:667–671, 2020; Eur J Case Rep Intern Med April 18, 2019

Pemphigus foliaceus Clin Exp Dermatol 43:817–818, 2018; Dermatol Online J Dec 16, 2014 Scleroderma Front Immunol Jan 10, 2019; Acta DV Croat 24:75–80, 2016 Palmar fasciitis J Clin Rheumatol 18:112, 2012; Clin Rheumatol 30:569–572, 2011 Paraneoplastic fasciitis and polyarthritis Int J Rheu Dis 20:1876– 1878, 2017 Herpes zoster – gangrenous or bullous Bazex syndrome Eur J Dermatol 17:557–558, 2007; Clin Exp Dermatol 29:429–430, 2004 Cowden’s syndrome Ectopic ACTH Clin Endocrinol (Oxf) 50:675–678, 1999; Southern Med J 77:518–520, 1984 Multicentric reticulohistiocytosis J Dtsch Dermtol Ges 17:746–748, 2019; JAAD 39:864–866, 1998; Med Pediatr Oncol 13:273–279, 1985 Sweet’s syndrome Cancer 72:2723–2731, 1993

Zosteriform metastases Clin Exp Dermatol 43:734–736, 2018; Indian J Pathol Microbiol 54:803–804, 2011; Indian J DV Leprol 76:447, 2010; J Dermatol Surg Oncol 18:97–100, 1992

Erythema annulare centrifugum Acta DV Croat 18:264–266, 2010

Eyelid lesions Cutis 70:291–293, 2002; eyelid swelling Dermatology 205:636, 2002; JAAD 37:362–364, 1997; J Surg Oncol 29:233–236, 1985

Hypertrichosis lanuginosa acquisita BJD 157:1087–1092, 2007; concurrent acanthosis nigricans, hypertrophy of the tongue, glossitis J Surg Oncol 68:199–203, 1998

Mask-like metastases Am J Dermatopathol 32:9–14, 2010 “Clown nose” Z Hautkr 65:929–931, 1990 Unilateral indurated plaque of axilla Dermatol Online J July 15, 2016

Erythema gyratum repens Granuloma annulare Acta DV 99:244–245, 2019

Paget’s disease of the nipple Acanthosis nigricans

Implantation metastases

Stiff person syndrome J Neurol Neurosurg Psychiatry 86:840–848, 2015

Dermatitis-like (eczematoid) Indian J Dermatol 60:106, 2015

Digital ischemia Acta Rheumatol Pot 41:378–379, 2016

Metastases to antecedent rhytidectomy scar JAAD 4:392–395, 2018

Erythromelalgia Int J Dermatol 51:878–880, 2012

Breast implant-associated anaplastic large cell lymphoma J Cutan Pathol 43:602–608, 2016; solid peri-implant mass; skin papules; seroma in the fibrous scar Int J Women’s Dermatol 3:140–144, 2017

Henoch-Schonlein purpura Semin Arthr Rheum 29:360–367, 2000

Inframammary fold involvement

Superficial thrombophlebitis Vasa 38:167–170, 2009 Vasculitis Clin Immunol 129:3–9, 2008

Pagetoid/Bowenoid Pigmented macule NEJM 377:1777, 2017 Mimicking angiosarcoma JAAD 48:635–636, 2003 Mimicking cutaneous infection Acta DV Croat 24:154–157, 2016; Clin Exp Dermatol 34:e409–410, 2009 Mimicking multiple dermatofibromas Int J Dermatol 55:574–576, 2016 Mimicking eruptive angiokeratomas Am J Dermatopathol 38:302– 304, 2016 Mimicking erythema annulare centrifugum Clin Exp Dermatol 41:906–910, 2016; Cutis 26:282–284, 1980 Mimicking granular cell tumor J Cutan Pathol 16:218–221, 1989 Mimicking granuloma annulare Mimicking keratoacanthoma

BREAST HYPERTROPHY (GYNECOMASTIA) AND BREAST MASSES Indian J Endocrinol Metab 18:150–158, 2014; Ped Derm 17:277– 281, 2000; JAAD 43:733–751, 2000

AUTOIMMUNE DISEASES Lupus mastitis (lupus panniculitis of the breast) – single or multiple painful nodules with erythema, poikiloderma, or ulcer overlying the nodules Acta Dermatovenereol Croat 25:305–306, 2017; red breast

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AD 142:398–399, 2006; red plaque of the breast (mimicking carcinoma erysipelatoides) JAAD 60:1074–1076, 2009; nodule JAAD 29:343–346, 1993

Ketoconazole Marijuana Methyldopa Metoclopramide

CONGENITAL

Nifedipine

Dermoid cyst

Nilutamide – anti-androgen

Hermaphroditism

Nitrosoureas

Neonatal breast enlargement – bilateral; due to falling maternal estrogen levels inducing neonatal prolactin secretion NEJM 360:1445, 2009

Omeprazole

Neonatal hypertrophy of the mammary glands – with neonatal lactation (“witch’s milk”)

Phenytoin

DEGENERATIVE

Reserpine

Old age NEJM 328:490–495, 1993

Risperidone

Paraplegia NEJM 328:490–495, 1993

Spironolactone

Penicillamine Arthritis Rheum 21:167–168, 1978 Phenothiazines Protease inhibitor (saquinavir, nelfinavir, indinavir) JAAD 46:284– 293, 2002

Testosterone

DRUGS Expert Opinion on Drug Safety 11:779–795, 2012; NEJM 315:1553, 1986 Alkylating agents Amiloride Amiodarone Amphetamines Anabolic steroids Androgens Anti-androgens Anti-HIV drugs, including nucleoside reverse transcriptase inhibitors, protease inhibitors, and non-nucleoside reverse transcriptase inhibitors – lipoatrophy, lipohypertrophy, gynecomastia; with metabolic syndrome JAAD 63:549–561, 2010 Bicalutamide (androgen-receptor inhibitor) – bilateral gynecomastia NEJM 367:1449, 2012 Busulfan Captopril Chorionic gonadotrophin NEJM 328:490–495, 1993 Cimetidine Cyproterone acetate Cytotoxic agents Diazepam Diethylpropion Digitalis Domperidone Estrogens Exogenous cortisol 5-Alpha reductase analogs Flutamide – anti-androgen GnRH analogs Gonadotropins

Tricyclic antidepressants Verapamil Vincristine

EXOGENOUS AGENTS Alcohol Breast implants Heroin Marijuana Oleomas – multiple subcutaneous oleomas due to injection with sesame seed oil BJD 149:1289–1290, 2003 Opioids Paraffinoma (sclerosing lipogranuloma) Acta Chir Plast 33:163–165, 1991; Plast Reconstr Surg 65:517–524, 1980

INFECTIONS AND INFESTATIONS Actinomycosis (Actinomyces israelii) – painful induration and swelling; fever and chills Clin Inf Dis 60:438,486–487, 2015 AIDS Ann Int Med 107:257, 1987 Brucellosis – breast abscess J Infect 33:219–220, 1996 Cat scratch disease JAD 47:803–804, 2002 Chromomycosis – Phialophora verrucosa BJD 152:560–564, 2005 Coccidioidomycosis – breast nodule or abscess Cryptococcosis – breast nodule or abscess Filariasis – Wuchereria bancrofti, Brugia malayi; chronic edema of the breast with elephantiasis Dermatol Clin 7:313–321, 1989 Leprosy Mastitis – Staphylococcus aureus; neonatal Staphylococcus aureus mastitis Am J Dis Child 129:1031–1034, 1975; Mycobacterium abscessus mastitis following body piercing Clin Inf Dis 33:131–134, 2001; lactation mastitis JAMA 289:1609–1612, 2003; medical tourism, breast implants, infection

Human growth hormone

Mycobacterium abscessus – breast abscesses due to adulterated intramammary silicone injections JAAD 50:450–454, 2004; mastitis Clin Inf Dis 33:131–134, 2001

Isoniazid

Mycobacterium avium-intracellulare – breast nodule or abscess

HAART therapy – gynecomastia Clin Inf Dis 33:891–893, 2001

Breast Hypertrophy (Gynecomastia) and Breast Masses Mycobacterium chelonae – breast nodule or abscess

NEOPLASTIC DISEASES

Mycobacterium fortuitum – breast nodule or abscess Clin Inf Dis 26:760–761, 1998

Adrenocortical tumors

Mycobacterium tuberculosis – tuberculous mastitis; breast nodule which may ulcerate with draining sinuses Indian J Inf Dis 87:135– 142, 2019 Mycobacterium xenopi – breast nodule or abscess Staphylococcus aureus, coagulase-negative (Staphylococcus epidermidis) – abscesses of the scalp and breast in the neonate Subareolar abscess

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Cutaneous radiation-associated angiosarcoma of the breast – livedoid violaceous plaques with nodules of the breast JAMADerm 149:973–974, 2013 Breast carcinoma, including male breast cancer – unilateral gynecomastia Cutis 69:98–102, 2002 Bronchial carcinoma Cystosarcoma phylloides Ductal papillomas Epidermoid cyst

INFLAMMATORY DISEASES

Erdheim-Chester disease Am J Surg Pathol 34:584–588, 2010

Cholesteroloma Breast J 25:1177–1181, 2019

Fibroadenomas – complex fibroadenoma, juvenile fibroadenoma, giant fibroadenoma

Eosinophilic cellulitis – red plaques of the breast AD 148:990–992, 2012 Granulomatous mastitis – abscess, sinus tract, or subcutaneous nodule of the breast The Breast Journal 14:588–590, 2008 Panniculitis – septal and lobular panniculitis with history of breast cancer Ann Med Surg 36:54–57, 2018

METABOLIC DISEASES Adolescent gynecomastia NEJM 328:490–495, 1993 Adrenal disease – increased peripheral conversion of estrogen Adrenocorticotropic hormone (ACTH) deficiency J Endocrinol Invest 10:127–129, 1987 Congenital adrenal hyperplasia Diabetes mellitus, type 1 – diabetic mastopathy Estrogen excess

hCG or aromatase-producing tumors – bilateral gynecomastia JAAD 53:660–662, 2005; metastatic nonseminomatous germ-cell tumor – hCG-­mediated hyperthyroidism and gynecomastia NEJM 373:2358–2369, 2015 Hepatoma Hybrid cysts – epidermoid and apocrine cyst Am J Dermatopathol 18:364–366, 1996 Leukemia – acute myelocytic leukemia BMJ Case Rep Aug 17, 2018; acute lymphoblastic leukemia masquerading as gynecomastia Am J Med 108:677–679, 2000 Lipomas Lymphoma – CTCL mimicking EAC in a child BJD 152:565–566, 2005; CTCL; primary and secondary, large cell B-cell lymphoma; anaplastic large cell lymphoma following textured implants Melanocytic nevi – giant congenital melanocytic nevi; premature thelarche (breast enlargement) BJD 173:1471–1478, 2015

Hemodialysis NEJM 328:490–495, 1993; Ann Int Med 69:67–72, 1968

Metastases – breast carcinoma, other primary malignancies (ovarian, melanoma, gastric carcinoma, head and neck squamous cell carcinoma) Case Rep Radiol Jan 8, 2019; chondrosarcomatous cutaneous metastases Am J Dermatopathol 18:538–542, 1996

Hyperthyroidism NEJM 328:490–495, 1993

Myxoid fibroadenoma Am J Surg Pathol 15:835–841, 1991

Hypogonadism NEJM 328:490–495, 1993

Ovarian follicular cysts

Liver disease NEJM 328:490–495, 1993

Ovarian granulosa cell tumors

Milk stasis during lactation JAMA 289:1609–1612, 2003

Pilomatrixomas

Obesity – pseudogigantomastia

Pituitary tumors

Physiologic – birth – maternal estrogens; puberty in boys JAMA 178:449–454, 1961; elderly men – testicular failure Am J Med 77:633–635, 1984; obesity – increased aromatase J Clin Endocrinol Metab 64:618–623, 1987; Am J Med 77:633–635, 1984

Prolactinoma – bilateral gynecomastia JAAD 53:660–662, 2005

Gravid macromastia Plast Reconstr Surg 80:121–124, 1987 Hemochromatosis – liver disease

Renal failure and dialysis Starvation, cachexia, refeeding NEJM 328:490–495, 1993; J Clin Endocrinol Metab 41:60–69, 1975 Steroid-binding globulins increased – bilateral gynecomastia JAAD 53:660–662, 2005 Steroid dehydrogenase deficiency Testicular failure JAAD 53:660–662, 2005 Testicular feminization – defective estrogen receptors Thyrotoxicosis Virginal breast hypertrophy – sudden massive enlargement of one or both breasts, girls ages 8–16 years – prominent veins, peau d’orange, and rarely necrosis Ped Derm 17:277–281, 2000

Testicular tumors – seminoma, interstitial cell tumor, Sertoli cell tumor, teratomas; all secrete human chorionic gonadotrophin NEJM 328:490–495, 1993

PRIMARY CUTANEOUS DISEASES Benign gynecomastia of the male breast Am J Med 77:633–635, 1984 Duct ectasia Erythroderma NEJM 328:490–495, 1993 Florid papillomatosis Gigantomastia Am J Dis Child 125:293, 1973 Gynecomastia – neonatal, puberty, elderly, cirrhosis, starvation, stress, male hypogonadism, prolactinoma, hyperthyroidism, renal failure and dialysis, ectopic HCG production (large cell lung cancer, hermaphroditism, type 1 diabetes mellitus

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 Drugs   Spironolactone   Cimetidine   Ketoconazole    Human growth hormone   Estrogens   hCG Anti-androgens   GnRH analogs   5-Alpha reductase inhibitors  Risperidone  Verapamil  Nifedipine  Omeprazole   Alkylating agents   HIV medications   Anabolic steroids  Alcohol  Opioids Uneven bilateral hypertrophy Aesth Plast Surg 18:399–403, 1994 Unilateral hypoplasia or hypertrophy Aesth Plast Surg 18:399–403, 1994

SYNDROMES Breast hypertrophy, erythema annulare centrifugum, generalized melanoderma, verrucae vulgaris, and SLE Acta DV (Stockh) 52:33, 1972 Byars-Jurkiewicz syndrome – giant fibroadenomas of the breast, secondary kyphosis, hypertrichosis, gingival fibromatosis Plast Reconstr Surg 27:608–612, 1961 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – annular erythematous edematous plaques of the face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of the lips (thick lips), lipoatrophy of the cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of the lateral forehead, gynecomastia, wide-spaced nipples, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, splenomegaly, protuberant abdomen Ped Derm 28:538–541, 2011; JAAD 62:487–495, 2010 Carney complex – breast myxomas with generalized breast enlargement JAAD 46:161–183, 2002 Cowden’s syndrome – fibrocystic disease leading to enlarged breasts H syndrome – autosomal recessive; facial telangiectasias; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, hyperpigmented hypertrichotic plaques; short stature, facial telangiectasia, gynecomastia, camptodactyly of fifth fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azoospermia, sensorineural hearing loss, cardiac anomalies (atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly); hepatosplenomegaly; Arabic Palestinian population; gluteal lipoatrophy; hyperpigmentation, sensorineural hearing loss, diabetes mellitus, hypogonadism; short stature; lymphadenopathy, hypertrichosis, heart anomalies, micropenis, scrotal masses, flexion contractures of the toes and PIP joints; hallux valgus, hyperpigmentation induration, and hypertrichosis of the inner thighs and shins (sclerodermoid), chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 (equilibrative nucleoside transporter) Ped Derm

33:602–614, 2016; JAAD 70;80–88, 2014; BJD 162:1132–1134, 2010; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008 Hermaphroditism Klinefelter’s syndrome – gynecomastia, scant hair on the beard, trunk, and extremities Klinefelter’s syndrome. Berlin: SpringerVerlag, 1984 Leprechaunism – Donohue’s syndrome – decreased subcutaneous tissue and muscle mass, characteristic facies, severe intrauterine growth retardation, broad nose, low-set ears, hypertrichosis of the forehead and cheeks, loose folded skin at flexures, gyrate folds of skin of the hands and feet; breasts, penis, clitoris hypertrophic Endocrinologie 26:205–209, 1988 Multifocal idiopathic fibrosclerosis (hyper-IgG4 syndrome) – sclerodermoid red plaque of the breast; fibrosis of the thyroid, mediastinum, retroperitoneum, orbits, pancreas, gallbladder AD 148:1335–1336, 2012 Myotonic dystrophy Peutz-Jeghers syndrome – bilateral gynecomastia due to bilateral Sertoli cell tumors of the testes JAAD 53:660–662, 2005 POEMS syndrome (Takatsuki syndrome, Crow-Fukase syndrome) (osteosclerotic myeloma) – peripheral edema, osteosclerotic bone lesions, peripheral polyneuropathy, hypothyroidism, and hypogonadism, hyperpigmented sclerodermoid plaque of the thighs, scrotal edema, testicular hypertrophy, gynecomastia Blood Reviews 21:285–299, 2007; JAAD 55:149–152, 2006; JAAD 45:969–970, 2001; JAAD 21:1061–1068, 1989; Cutis 61:329–334, 1998; Nippon Shinson 26:2444–2456, 1968

TRAUMA Physical trauma

VASCULAR DISEASES Angiosarcoma Am Surg 62:668–672, 1996; angiosarcoma of the breast post–irradiation for breast cancer – late thickening, edema, or induration of the breast JAAD 49:532–538, 2003 Atypical vascular lesion (lymphatic type) – vascular papule of the breast JAMADerm 149:1341–1342, 2013; Am J Clin Pathol 102:757–763, 1994 Venous malformation BJD 162:350–356, 2010

BREAST LESIONS AUTOIMMUNE DISEASES Allergic contact dermatitis Bullous pemphigoid; localized bullous pemphigoid at the site of radiation – tense bullae JAMADerm 149:1427–1428, 2013; Radiation Oncol 82:5–9, 2007 Lupus mastitis – subcutaneous nodules of the breast with atrophy, ulceration, erythema, poikiloderma, hyperkeratosis, color changes, discoid lesions Ann Diagn Pathol 17:230–233, 2013; JAAD 60:1074–1076, 2009; AD 142:398–399, 2006; sclerosis of the breast JAAD 29:343–346, 1993; subacute cutaneous lupus erythematosus – personal observation Morphea – personal observation Pemphigus erythematosus Progressive systemic sclerosis

Breast Lesions

CONGENITAL LESIONS

Scabies

Accessory axillary breasts – personal observation

Subareolar abscess

Accessory nipple Neonatal mastitis JAAD 80:1483–1494, 2019

DRUG Corticosteroid acne Corticosteroid atrophy Indinavir – breast hypertrophy J Clin Inf Dis 25:937–938, 1997

159

Syphilis, secondary; tertiary – breast ulcerations from gumma NEJM 373:2069, 2015 Tinea versicolor

INFILTRATIVE DISEASES Amyloidosis – primary cutaneous – pigmentation of the breast AD 123:1557–1562, 1982

Iohexol (intravenous contrast material) – annular plaque of the breast J Drugs in Dermtol 10:802–804, 2011

Reticular erythematous mucinosis (REM) syndrome – red reticulated plaques of the breasts and central back BJD 169:1207–1211, 2013

Lotrisone atrophy – personal observation

Urticaria pigmentosa

Overanticoagulation – hemorrhage – personal observation

EXOGENOUS AGENTS Hair sinus of the breast Irritant contact dermatitis JAAD 80:1483–1494, 2019 Silicone migration

INFECTIONS AND INFESTATIONS

INFLAMMATORY DISEASES Acute mastitis Cystic neutrophilic granulomatous mastitis – abscess–like lesion of the breast; Corynebacterium kroppenstedtii, C. amycolatum, C. tuberculostearicum, C. accolens, C. striatum, C. minutissimum Clin Inf Dis 59:410,454–455, 2014 Eosinophilic fasciitis – personal observation Hidradenitis suppurativa JAAD 80:1483–1494, 2019

Actinomycosis (Actinomyces israelii) – painful induration and swelling; fever and chills Clin Inf Dis 60:438,486–487, 2015

Idiopathic granulomatous mastitis – red ulcerated nodules of the breast Cutis 103:38–42, 2019

Breast abscess Clin Inf Dis 59:410,454–455, 2014   Anaerobic species in non-puerperal women   Brucella melitensis J Infect 33:219–220, 1996   Cat scratch disease Clin Inf Dis 59:410,454–455, 2014   Cryptococcus neoformans Scand J Infe Dis 34:309–310, 2002  Cystic neutrophilic granulomatous mastitis presenting as recurrent breast abscess; Corynebacterium species include C. kroppenstedtii, C. amycolatum, C. tuberculostearicum, C. accolens, C. striatum, C. minutissimum Clin Inf Dis 59:410, 454–455, 2014   Escherichia coli   Granulomatosis with polyangiitis Acta Clin Belg 54:207–210, 1999   Mycobacterium chelonei    Periareolar pilonidal abscesses  Sarcoidosis Pathologica 102:104–107, 2010    Squamous metaplasia of lactiferous ducts

Pyoderma gangrenosum, postoperative JAAD 73:615–622, 2015

Borrelial lymphocytoma Clin Inf Dis 63:914–921, 2016 Botryomycosis – Staphylococcus aureus; multiple herpetiform and grouped papulopustules Candidal mastitis – areolar erythema and fissuring JAAD 80:1483– 1494, 2019 Cryptococcosis – breast mass J Clin Inf Dis 1166–1169, 1995 Filariasis – breast edema JAAD 73:929–944, 2015 Herpes simplex, including eczema herpeticum Herpes zoster Infectious eczematoid dermatitis Lyme disease – personal observation Mastitis Mycobacterium abscessus – mastitis Clin Inf Dis 33:131–134, 2001 Mycobacterium tuberculosis – nodular tuberculous mastitis (solitary or multiple palpable masses); sinus tract, ulcer; disseminated tuberculous mastitis; tuberculous abscess Int J Inf Dis 87:135–142, 2019; JAAD 80:1483–1494, 2019

Sarcoid

METABOLIC DISEASES Kwashiorkor – personal observation Porphyria cutanea tarda – sclerosis – personal observation Pruritic urticarial papules and plaques of pregnancy (PUPPP) Purpura fulminans – personal observation

NEOPLASTIC DISEASES Angiosarcoma – following breast irradiation for breast cancer JAAD 54:499–504, 2006 Becker’s nevus with homolateral mammary hypoplasia Cutis 68:123–124, 2001; Am J Med Genet 68:357–361, 1997 Breast cancer, primary – women, men JAAD 80:1467–1481, 2019; Eur J Surg Oncol 19:581–586, 1993   Breast cancer, increased risk JAAD 80:1467–1481, 2019   Ataxia telangiectasia   Cowden’s syndrome   Bloom’s syndrome   Down’s syndrome   Fanconi’s anemia   McCune-Albright syndrome   Muir-Torre syndrome    Nevoid basal cell carcinoma syndrome   Peutz-Jeghers syndrome   Poland syndrome   Scalp-ear-nipple syndrome Breast cyst JAAD 80:1467–1481, 2019 Cutaneous T-cell lymphoma JAAD 80:1467–1481, 2019

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Fibroadenoma JAAD 80:1467–1481, 2019

PSYCHOCUTANEOUS DISORDERS

Fibrocystic disease of the breast JAAD 80:1467–1481, 2019

Factitial dermatitis – personal observation

Fibromatosis JAAD 80:1467–1481, 2019 Hamartoma JAAD 80:1467–1481, 2019

Neurotic excoriations – personal observation

Keloids Lactating adenoma JAAD 80:1467–1481, 2019

SYNDROMES

Leiomyomas – personal observation

Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears, hooked nose, sparse hair, hypohidrosis, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene (encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993

Leukemic infiltrates of the breast JAAD 43:733–751, 2000 Lymphoma – primary cutaneous large cell B-cell lymphoma, leg type – red plaque JAMADerm 155:1420–1421, 2019; cutaneous T-cell lymphoma; immunoblastic lymphoma; Burkitt’s lymphoma – indurated breasts JAMADerm 151:223–224, 2015; subcutaneous panniculitis-like T-cell lymphoma – personal observation; intravascular B-cell lymphoma – personal observation Metastatic breast carcinoma, including carcinoma erysipelatoides, carcinoma telangiectaticum – personal observation Nevus sebaceus with tubular apocrine adenoma and syringocystadenoma papilliferum – velvety, grouped nodules BJD 156:1397– 1399, 2007 Paget’s disease JAAD 80:1467–1481, 2019 Phylloides tumor JAAD 80:1467–1481, 2019 Cutaneous histiocytic sarcoma – red nodule of the breast JAAD 76:S5–7, 2017 Sclerosis of the breast   Lupus mastitis JAAD 29:343–346, 1993  Morphea   Scirrhous carcinoma   Scleroderma (progressive systemic sclerosis)   Inflammatory cancer of the breast

Becker’s nevus syndrome – breast hypoplasia Am J Med Genet 68:357–361, 1997; supernumerary nipples BJD 136:471–472, 1997; Clin Exp Dermatol 22:240–241, 1997; hypoplastic nipples Am J Med Genet 77:76–77, 1998 Bloom’s syndrome – breast cancer Byars-Jurkiewicz syndrome – gingival fibromatosis, hypertrichosis, fibroadenomas of the breast Carney complex – breast myxomas with generalized breast enlargement JAAD 46:161–183, 2002; Carney complex – acromegaly, facial lentigines, cutaneous breast myxoma, blue nevus of the vulva; gain-of-function mutation of PRKACB (catalytic subunit alpha of cAMP-dependent protein kinase) NEJM 370:1065–1067, 2014 Cowden’s syndrome – benign gynecomastia in male; breast cancer Fanconi’s anemia – breast cancer

Syringomas

Goltz’s syndrome

PRIMARY CUTANEOUS DISEASES

Hypomelanosis of Ito

Atopic dermatitis JAAD 80:1483–1494, 2019

Incontinentia pigmenti – breast hypoplasia JAAD 64:508–515, 2011

Contact dermatitis – allergic, irritant

Klinefelter’s syndrome – breast cancer

Confluent and reticulated papillomatosis JAAD 80:1483–1494, 2019

McCune-Albright syndrome – breast cancer

Erosive adenomatosis of the nipple

Muir-Torre syndrome – breast cancer

Erythema craquelé

Nevoid basal cell carcinoma syndrome – breast cancer

Fox-Fordyce disease JAAD 80:1483–1494, 2019

Poland syndrome

Granuloma annulare

Reticular erythematous mucinosis syndrome (REM syndrome) – personal observation

Hyperkeratosis of the nipple and areola AD 137:1327–1328, 2001 Ichthyosis en confetti – breast hypoplasia JAMADerm 151:64–69, 2015 Intertrigo JAAD 80:1483–1494, 2019 Lactational dermatitis – fever, red plaque; Staph, Strep, E. coli JAAD 80:1483–1494, 2019

Hypohidrotic ectodermal dysplasia – bilateral amastia BJD 171:671–673, 2014

Romberg syndrome Arch Neurol 39:44–49, 1982 Neurofibromatosis, including segmental neurofibromatosis – personal observation Peutz-Jeghers syndrome – breast cancer Scalp-ear-nipple syndrome – amastia, athelia, hypothelia

Lichen planus, planopilaris – personal observation; annular atrophic plaques of the breasts JAMADerm 155:1187–1188, 2019

Steatocystoma multiplex

Lichen sclerosus et atrophicus

Ulnar-mammary syndrome – autosomal dominant; ulnar defects, nipple or apocrine gland hypoplasia; wide face, nasal base and tip, protruding chin; cardiac abnormalities TXB3 mutation Eplasty 27:14:ic35, e collection 2014, 2014 September

Parapsoriasis en plaque Pityriasis rosea Pityriasis rubra pilaris Psoriasis JAAD 80:1483–1494, 2019

Sweet’s syndrome

Pustular psoriasis

TRAUMA

Striae

Hypertrophic scars secondary to breastfeeding

Superficial vegetating pyoderma

Jogger’s nipples

Buffalo Hump (Cervicodorsal Lipodystrophy) Postradiation lichen sclerosus JAMADerm 153:1067–1069, 2017 Postradiation morphea Pressure-induced panniculitis following back surgery – personal observation Radiation dermatitis, acute and chronic JAAD 80:1483–1494, 2019 Radiation recall dermatitis JAAD 80:1483–1494, 2019

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CORTICOTROPIN-DEPENDENT CUSHING’S SYNDROME Bronchial carcinoid – with ectopic ACTH production Chin Med J 108:338–341, 1995; Mayo Clin Proc 65:1314–1321, 1990; Clin Endocrinol 24:523–529, 1986; ectopic corticotropin-releasing hormone NEJM 332:791–803, 1995 Cervical carcinoma of the uterus with ectopic ACTH production Jpn J Cancer Res 82:710–715, 1991

VASCULAR DISORDERS Atypical vascular lesion (lymphatic type) – vascular papule of the breast JAMADerm 149:1341–1342, 2013; Am J Clin Pathol 102:757–763, 1994

Ectopic ACTH syndrome due to small cell carcinoma Chang Keng I Hsueh 17:371–377, 1994; Am J Med 62:303–307, 1977 Medullary carcinoma of the thyroid gland with ectopic ACTH production Nippon Naibunpi Gakkai Zasshi 53:1279–1291, 1977

Breast lymphedema

Neuroendocrine islet cell tumor Gut 26:426–428, 1985

Cherry angioma

Ovarian steroid tumors Am J Surg Pathol 11:835–845, 1987

Diffuse dermal angiomatosis (reactive angioendotheliomatosis), including diffuse dermal angiomatosis of the breast; reticulated erythema (livedo reticularis) with ulcerations of the breasts; multiple red-violaceous purpuric patches; seen in patients with breast reduction Cutis 103:181–184, 2019; JAAD 71:1212–1217, 2014; AD 144:693–694, 2008; AD 142:343–347, 2006

Pituitary micro- and macroadenomas NEJM 332:791–803, 1995 Pulmonary tumorlets (neuroendocrine cells) – corticotropin secretion NEJM 339:883–886, 1998 Thymic carcinoid – with ectopic ACTH production Chin Med J 108:338–341, 1995; Thorax 49:357–360, 1994

Fat emboli – petechiae Granulomatosis with polyangiitis – breast necrosis, livedo reticularis, arthralgias Rev Med Brux 33:112–115, 2012

CORTICOTROPIN-INDEPENDENT CUSHING’S SYNDROME

Ischemic necrosis – following internal mammary artery after bypass graft – personal observation

Adrenal carcinoma NEJM 332:791–803, 1995

Livedo reticularis of the breast – personal observation Lymphangioma circumscriptum Lymphedema – mediastinal lymphoma – personal observation Superficial thrombophlebitis of the breast (Mondor’s disease) JAAD 80:1483–1494, 2019 Thrombosed angioma Venous malformation BJD 162:350–356, 2010

 UFFALO HUMP (CERVICODORSAL B LIPODYSTROPHY) DRUG-INDUCED Abacavir/lamivudine/zidovudine JAMA 309:1289–1290, 2013 Exogenous corticosteroids Transplantation 59:729–736, 1995; Arch Int Med 140:1507–1508, 1980 Indinavir NEJM 339:1296–1297, 1998 Megestrol acetate – glucocorticoid-like activity Arch Int Med 157:1651–1656, 1997

INFECTIONS HIV infection – lipodystrophy of HIV infection NEJM 339:1296–1297, 1998; Lancet 35:867–870, 1998

ENDOCRINE DISORDERS Cushing’s syndrome Ann Int Med 138:980–991, 2003; bilateral macronodular adrenal hyperplasia NEJM 369:2115–2125, 2013; NEJM 369:2105–2114, 2013

Bilateral adrenocortical adenomas Surg Today 24:538–543, 1994 Familial Cushing’s syndrome – micronodular adrenocortical dysplasia Arch Int Med 148:1133–1136, 1988 Macronodular adrenal hyperplasia Endocrinol Jpn 36:101–116, 1989 Micronodular adrenal hyperplasia Endocrinol Jpn 36:101–116, 1989 Pigmented adenoma of the adrenal cortex Urology 7:641–645, 1976 Primary adrenocortical nodular hyperplasia associated with Carney complex J Clin Endocrinol Metab 82:1274–1278, 1997; Nippon Naibunpi Gakkai Zasshi 68:607–622, 1992 Pseudo-Cushing’s Syndrome Chronic alcoholism Clin Endocrinol (Oxf) 16:73–76, 1982 Common obesity of middle age Adv Exp Med Biol 116:279–280, 1979 Depression – hypercortisolism Ann NY Acad Sci 771:716–729, 1995; NEJM 332:791–803, 1995

MISCELLANEOUS Benign symmetric lipomatosis (Madelung’s disease) Ann Plast Surg 41:671–673, 1998 Cortisol hyperreactive syndrome – hypocortisolism and Cushing’s syndrome-like manifestations J Clin Endocrinol Metab 70:729–737, 1990 Food-dependent Cushing’s syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide NEJM 327:974–980, 1992; NEJM 327:981–986, 1992 Lipoma(s) Mycobacterium tuberculosis – CNS tuberculosis – with Cushing’s syndrome J Neurol Sci 14:341–357, 1971 Paraneoplastic Cushing’s syndrome Eur J Pediatr 153:784–791, 1994

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Renal adenocarcinoma – paraneoplastic Cushing’s syndrome Semin Urol 7:158–171, 1989

BULLAE AND/OR VESICLES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Acquired subepidermal autoimmune bullous disorders – bullous pemphigoid, mucous membrane pemphigoid, anti-laminin 332 mucous membrane pemphigoid, anti-p200 pemphigoid, anti-plectin pemphigoid, linear IgA disease, pemphigoid gestations, lichen planus pemphigoides, epidermolysis bullosa acquisita BJD 169:100–105, 2013 Allergic contact dermatitis, including poison ivy, nickel sensitivity resembling bullous pemphigoid; cinnamic aldehyde Dermatosen 6:186–187, 1988; complicating venous stasis; allergic contact dermatitis to henna – bullae of the palm Ped Derm 28:580–581, 2011; Plantago spp. Clin Dermatol 38:176–192, 2020 Anti-laminin 332 mucous membrane pemphigoid – after diphtheria/ tetanus vaccination JAMADerm 149:858–862, 2013 Anti-laminin-gamma-1 (anti-p200) pemphigoid – vesicles and bullae; autoantibody targeting laminin 311 of the lower lamina lucida; strong association with psoriasis JAMADerm 53:1185–1186, 2017; J Eur Acad Dermatol Venereol, Sep 29, 2016; JAAD 71:185–191, 2014; BJD 168:1367–1369, 2013; BJD 168:647–655, 2013; Ann Dermatol Venereol 140:784–787, 2013; BJD 167:1179–1183, 2012; Dermatol 218:265–271, 2009; J Dermatol 34:1–8, 2007; JID 106:1333, 1996; Med J Rec 130:246–248, 1929 Autoantibodies to BP 230 and laminin gamma 1 – bullae of the lips, periumbilical bullae, giant bullae of the palms BJD 175:619–621, 2016 Autoimmune estrogen dermatitis – papulovesicular eruptions JAAD 32:25–31, 1995; bullae JAAD 49:130–132, 2003 Autoimmune progesterone dermatitis – resembling dermatitis herpetiformis JAMA 190:35–38, 1964 Bowel-associated dermatitis-arthritis syndrome – vesicles evolving into pustules AD 138:973-978, 2002 Brunsting-Perry cicatricial pemphigoid – scalp erosions, bullae, oral bullae and ulcers, scarring alopecia BJD 170:743–745, 2014 Bullous disease with IgA vs. collagen VII and IgG vs. laminin 332 – urticarial plaques and bullae and oral erosions BJD 167:938–941, 2012 Bullous eruption in CREST syndrome, primary biliary cirrhosis and Sjögren’s syndrome JAAD 29:648–650, 1993 Bullous pemphigoid NEJM 373:1659, 2015; of the soles JAMADerm 151:99–100, 2015; following varicella or herpes zoster Ped Derm 31:748–749, 2014; anti-105 kD and anti-200 kD bullous pemphigoid-like disorders AD 135:173–176, 1999; palmoplantar vesicobullae BJD 156:1075–1078, 2007; Acta DV 84:253–254, 2004; bullous pemphigoid in infancy with palmar and plantar bullae Ped Derm 15:108–111, 1998; anti-p105 pemphigoid AD 130:343–347, 1994; anti-p200 pemphigoid BJD 148:1058–1060, 2003; JAAD 46:786– 789, 2002; BJD 143:1043–1049, 2000; anti-p450 pemphigoid Adv Dermatol 16:113–157, 2000; anti-­laminin 332 pemphigoid without mucous membrane involvement BJD 163:1120–1122, 2010; anti-laminin gamma-1 pemphigoid antibodies (200 kDa protein) BJD 163:1134–1136, 2010; J Dermatol 34:1–8, 2007; anti-p200 bullous pemphigoid – bullae of the palms, generalized with oral ulcers and conjunctival erosions BJD 160:462–464, 2009; oral bullae of the hands and feet in infancy AD 143:215–220, 2007; Brunsting-Perry

pemphigoid (possibly epidermolysis bullosa acquisita) – bullae with atrophic scarring of the head, face, neck JAAD 61:715–719, 2009; giant bullae Ped Derm 27:537–539, 2010; bullous pemphigoid associated with renal allograft rejection JAAD 65:217–219, 2011; IgA anti-p200 pemphigoid (p200 is laminin gamma 1) – blisters with serpiginous urticarial and annular plaques AD 147:1306–1310, 2011; localized bullous pemphigoid at the site of radiation – tense bullae JAMADerm 149:1427–1428, 2013; Radiation Oncol 82:5–9, 2007; bullous pemphigoid in patients negative for IgG to BP180 NC16A domain JAMADerm 154:347–350, 2018 Chronic granulomatous disease – vesicular eruptions JAAD 36:899–907, 1997 Cicatricial pemphigoid (mucous membrane pemphigoid) – bullae of the upper trunk and head JAAD 64:1199–1200, 2011; AD 138:370– 379, 2002; generalized bullae BJD 68:128–131, 1956; IgG, IgA, anti-epiligrin JAAD 42:841–844, 2000; JAAD 40:637–639, 1999; AD 130:1521–1529, 1994; bullae of the soft palate Oral Surg 66:37–40, 1988; anti-laminin 332 (anti-epiligrin) cicatricial pemphigoid – blister on bulbar conjunctivum BJD 162:898–899, 2010 Cicatricial pemphigoid-like syndrome due to linear IgA disease directed against a 290 kD antigen JAAD 31:884–888, 1994 Dermatitis herpetiformis – elbows, knees, buttocks, shoulders, trunk, face, and scalp JAAD 64:1017–1024, 2011; JAMA 3:225– 229, 1884; hemorrhagic bullae of the palms and soles Ped Derm 11:319–322, 1994; oral bullae Oral Surg 62:77–80, 1986 Dermatomyositis – vesiculobullous JAAD 49:1136–1139, 2003 Am J Dermatopathol 20:170–174, 1998; with gynecologic malignancies JAAD 34:391–394, 1996; with nasopharyngeal carcinoma Ann Acad Med Singapore 28:855–857, 1999 Epidermolysis bullosa acquisita – BJD 171:1022–1030, 2014; IgG and/or IgA BJD 165:92–98, 2011; AD 135:173–176, 1999; Dermatologic Clinics 11:535–547, 1993; annular bullae BJD 147:592–597, 2002; in children Ped Derm 12:16–20, 1995; oral bullae Rook p. 3085, 1998, Sixth Edition; AD 123:772–776, 1987; of the feet; Brunsting-Perry IgG epidermolysis bullosa acquisita – scalp ulcers BJD 165:92–98, 2011; IgM epidermolysis bullosa acquisita – bullae of the fingers, elbows, dorsal hands BJD 173:1566–1568, 2015; Fogo selvagem (endemic pemphigus) JID 107:68–75, 1996; JAAD 32:949–956, 1995 Graft vs. host disease, acute or chronic – bullae AD 138:924–934, 2002; JAAD 38:369–392, 1998; varicella-like, TEN-like AD 134:602– 612, 1998; bullous scleroderma-like changes in chronic GVHD BJD 171:63–68, 2014; AD 121:1189–1192, 1985 Id reaction IgA-mediated epidermolysis bullosa acquisita JAAD 54:734–736, 2006 IgA pemphigus – vesicles, pustules, circinate plaques JAAD 82:1386–1392, 2020; BJD 171:650–656, 2014 IgM bullous disease – associated with IgM gammopathy BJD 150:392–394, 2004 Intraepidermal neutrophilic IgA dermatosis JAAD 31:502–504, 1994 (IgA pemphigus); intraoral blisters JAAD 20:89–97, 1989; IgA pemphigus – vesicopustules in a 1-month-old JAAD 48:S22–24, 2003 Lichen planus pemphigoides – bullae and flat-topped papules Ped Derm 26:569–574, 2009; AD 139:1363–1368, 2003; JAAD 36:638– 640, 1997; BJD 125:263–271, 1991; JAAD 22:626–631, 1990; palmar bullae AD 146:439–444, 2010; associated with PUVA BJD 142:509–512, 2002; ramipril (ACE inhibitor) BJD 136:412–414, 1997 Linear IgA disease (chronic bullous disease of childhood) – perioral, eyelids, ears, scalp, perineum, vulva; annular polycyclic bullae;

Bullae and/or Vesicles palmar and plantar bullae in infancy; may have hemorrhagic bullae; oral ulcers JAAD 50:109–115, 2004; JAAD 22:362–365, 1990; Ann DV 114:1358–1359, 1987; perfect annulus with peripheral bullae JAMADerm 155:373–374, 2019; conjunctivitis Ped Derm 15:108– 111, 1998; neonatal linear IgA disease Ped Derm 10:171–176, 1993; oral bullae; targetoid bullae BJD 169:210–211, 2013 Linear IgA/IgG bullous dermatosis – targetoid, urticarial, herpetiform lesions, confluent bullae BJD 177:212–222, 2017; dyshidrosiform bullae of the palms, herpetiform bullae, cutaneous erosions, tongue erosions JAMADerm 149:1308–1313, 2013 Lupus erythematosus – systemic lupus – bullous sunburn reaction Rook pp. 2472–2473, 1998, Sixth Edition; bullous dermatosis of SLE (annular bullae) – face, neck, upper trunk, oral bullae JAMADerm 151:539–543, 2015; JAMADerm 150:771–772, 2014; Ped Derm 27:373–376, 2010; Pediatr 12:138–144, 1995; JAAD 27:389–394, 1992; Arthritis Rheum 21:58–61, 1978; subacute cutaneous LE Australas J Dermatol 41:234–237, 2000; Z. Hautkr 67:220–223, 1991; giant bullae and multiple bullae Ped Derm 27:197–198, 2010; lupus panniculitis – plaque with bullae Fitzpatrick J of Clin Derm 2:32–34, 1994; bullous discoid lupus with targetoid lesions Dermatologica 122:6–10, 1961; subacute cutaneous lupus erythematosus – annular and polycyclic lesions with vesicles at border Med Clin North Am 73:1073–1090, 1989; JAAD 19:1957–1062, 1988; SCLE – toxic epidermal necrolysis-like JAAD 16:1265–1267, 1987 Morphea, bullous JAAD 30:937–943, 1994; Dermatology 119:341, 1959; unilateral edema and bullae preceding linear morphea Ped Derm 24:147–150, 2007 Mucous membrane pemphigoid – generalized bullae with perianal ulcers and esophageal ulcers; IgG and IgA antibodies to laminin 332 and type XVII collagen BJD 166:1116–1120, 2012 Pemphigoid gestationis (formerly herpes gestationis) – annular erythematous vesicular plaques JAAD 70:957-959, 2014; Cutis 88:21–26, 2011; BJD 157:388–389, 2007; JAAD 55:823–828, 2006; JAAD 40:847–849, 1999; JAAD 17:539–556, 1987; Clin Exp Dermatol 7:65–73, 1982; concentric bullae JAMADerm 150:445– 446, 2014; herpetiform blisters – antibody vs. NC16A portion of bullous pemphigoid antigen 180 BJD 172:120–129, 2015

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plaques, vesicles, crusts, ulcers; prominent involvement of the palms and soles; sparing of the trunk Ped Derm 24:211–215, 2007 Rheumatoid arthritis – rheumatoid neutrophilic dermatitis – vesicular or bullous JAAD 52:916–918, 2005; Cutis 60:203–205, 1997; bullae due to arteritis BJD 77:207–210, 1965 Systemic contact dermatitis to corticosteroids – red plaques with bullae BJD 172:300–302, 2015

CONGENITAL DISORDERS Aplasia cutis congenita – bulla of the scalp Arch Dis Child 23:61– 62, 1948 Congenital erosive and vesicular dermatosis with reticulate supple scarring – widespread erosions, low-set ears, syndactyly Ped Derm 26:735–738, 2009; JAAD 58:S104–106, 2008; Ped Derm 24:384–386, 2007; Ped Derm 22:55–59, 2005; Clin Exp Derm 30:146–148, 2004; JAAD 45:946–948,2001; Ped Derm 15:214–218, 1998; Dermatol 194:278–280, 1997; JAAD 32:873–877, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985 Neonatal sucking blisters – fingers, lips, forearms Pediatrics 32:1099–1101, 1963 Transient bullous dermolysis of the newborn with pseudosyndactyly – mutation in COL7A1; subtype of dystrophic epidermolysis bullosa BJD 157:179–182, 2007; JAAD 40:471–476, 1999; AD 129:109– 1210, 1993; JAAD 21:708–713, 1989; AD 121:1429–1438, 1985

DEGENERATIVE DISORDERS Hereditary sensory and autonomic neuropathy type I – calluses over metatarsal heads which blister, necrose, and ulcerate Rook p. 2779, 1998, Sixth Edition Neuropathic bullae – personal observation Reflex sympathetic dystrophy – bulla and leg ulceration JAAD 44:1050, 2001; JAAD 35:843–845, 1996; JAAD 28:29–32, 1993

Pemphigoid vegetans – oral bullae of palate and gingivae Arch Dermatol Res 279:S30–37, 1987; Int J Derm 25:17–27, 1986

DRUG-INDUCED

Pemphigus erythematosus NEJM 369:2438–2449, 2013

Acral dysesthesia syndrome – bullae of the hands and feet with systemic chemotherapy including cytosine arabinoside, doxorubicin, and polyethylene glycol-coated liposomal doxorubicin AD 136:1475–1480, 2000; chemotherapy-induced hand-foot syndrome (acral dysesthesia syndrome) (palmoplantar erythrodysesthesia syndrome) – pegylated liposomal doxorubicin, capecitabine, 5-fluorouracil, cytarabine, docetaxel, sorafenib, sunitinib, axitinib, pazopanib, regorafenib, vemurafenib JAAD 71:787–794, 2014

Pemphigus foliaceus AD 148:1173–1178, 2012 Pemphigus herpetiformis (vesicles) – annular erythematous patches with hyperpigmentation with or without vesicles; rosette lesions; annular arcuate red plaques with edematous borders with erosions and vesicles; red plaque with vesicles, circinate desquamation, erosions, urticarial lesions Ped Derm 34:342–346, 2017; JAAD 70:780–787, 2014; Ped Derm 30:760–762, 2013; AD 148:531–536, 2012; Ped Derm 27:488–491, 2010; JAAD 34:40–46, 1996 Pemphigus vegetans, Neumann type – giant cobblestoning with vegetative intertriginous plaques and blisters; oral bullae AD 145:715–720, 2009 Pemphigus vulgaris – bullae, erosions Clin Dermatol 31:374–381, 2013; JID 132:776–784, 2012; oral bullae Oral Surg 54:656–662, 1982; neonatal pemphigus Ped Derm 10:169–170, 1993; pemphigus with giant lymph node hyperplasia JAAD 26:105–109, 1992; association with autoimmune thyroid disease, rheumatoid arthritis, type 1 diabetes mellitus BJD 172:729–738, 2015 Pemphigus- and pemphigoid-like lesions with acquired palmoplantar keratoderma with tripe pattern – antibodies to desmocollin 3 BJD 157:168–173, 2007 Perforating neutrophilic and granulomatous dermatitis of the newborn – cutaneous eruption of immunodeficiency; papules,

Amiodarone JAAD 31:801–811, 1994 Anti-PD-1 therapy (atezolizumab, nivolumab, pembrolizumab, durvalumab) – bullous dermatoses (bullous pemphigoid, IgA dermatosis) – hemorrhagic bullae, urticarial plaques, oral ulcers JAAD 79:1081–1088, 2018 Benznidazole – toxic epidermal necrolysis BJD 175:604–607, 2016 Bromoderma AD 115:1334–1335, 1979 Bullous pemphigoid – drug-induced – amoxicillin J Drugs Dermatol 5:562–564, 2006; ciprofloxacin JAAD 42:847, 2000; furosemide AD 112:75–77, 1976; penicillamine JAAD 35:732–742, 1996; AD 123:1119–1120, 1987; penicillin JAAD 18:345–349, 1988; ibuprofen, phenacetin, Cuprimine, ampicillin Clin Exp Dermatol 15:50–52, 1990; spironolactone AD 132:272–276, 1996; Azulfidine, salicylazosulfapyridine, phenacetin AD 1120:1196–1199, 1984; Novascabin, sulfasalazine, Novoscabin, topical 5FU, PUVA AD 115:988–989, 1979; enalapril JAAD 29:879–882, 1993; Amoxil,

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chloroquine; galantamine hydrobromide Cutis 83:139–140, 2009; spironolactone, chloroquine, beta-blockers JAMADerm 149:243– 245, 2013; linagliptin (2-peptidyl peptidase 4 (DPP-4) inhibitors – bullous pemphigoid JAMADerm 152:224–226, 2016; sitagliptin JAMADerm 149:243–245, 2013; vildagliptin Fundam Clin Pharmacol 29:112–114, 2015; dipeptidyl peptidase-4 inhibitors BJD 175:296– 301, 2016; neurologic and psychiatric drugs JAAD 81:250–253, 2019; dipeptidyl peptidase-4 inhibitors (vildagliptin) JAAD Oct. 5, 2018 Cabozantinib – VEGFR2 inhibitor; c-met; RET multitargets; tyrosine kinase inhibitor; hand-foot skin reactions with bullae, hyperkeratosis, acral erythema; skin and hair depigmentation, splinter hemorrhages, xerosis, red scrotum JAMADerm 151:170–177, 2015 Calcipotriene – bullous phototoxicity JAAD 62:1081–1082, 2010 Cantharidin for warts Checkpoint inhibitors – immunobullous disorders JAAD 80:990–997, 2019 Chemotherapy-induced acral erythema – bullous variant – methotrexate, cytarabine AD 132:590–591, 1996; Cutis 51:175–179, 1993 Cicatricial pemphigoid – drug-induced – topical pilocarpine, topical demecarium, practolol, topical echothiophate iodide, sulfadoxine, penicillamine JAAD 35:732–742, 1996; clonidine BJD 102:715–718, 1980; bromide, indomethacin, idoxuridine, epinephrine Cinnarizine – lichen planus pemphigoides-like eruption BJD 112:607–613, 1985 Cladribine – bullous reactions JAAD 71:203–214, 2014 Cyclosporine – pseudoporphyria cutanea tarda AD 139:1373–1374, 2003 Dilantin Dipyrone-induced pemphigus Doxorubicin – personal observation Doxycycline photodermatitis – personal observation Drug-induced thrombocytopenia – oral hemorrhagic bullae Cutis 62:193–195, 1998 Drug reaction with eosinophilia and systemic symptoms (DRESS) – morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, facial edema, lymphadenopathy JAAD 68:693–705, 2013; Efalizumab – bullous pemphigoid JAAD 62:161–162, 2010 Enoxaparin sodium (low molecular weight heparin)-induced bullous pemphigoid JAAD 51:141–142, 2004 Epsilon aminocaproic acid infusion JAAD 27:880–882, 1992 Estrogen dermatitis – papulovesicular JAAD 32:25–31, 1995 Etoposide – extravasation; edematous bullous red hand Ped Derm 29:264–269, 2012 Extravasation from intravenous infusion Finasteride – pseudoporphyria cutanea tarda AD 147:747–748, 2011 Fixed drug eruption – generalized bullous fixed drug eruption JAAD 70:539–548, 2014; generalized fixed drug eruptions BJD 168:726– 732, 2013 Fludarabine-induced paraneoplastic pemphigus JAAD 58:545–570, 2008; bullous reactions JAAD 71:203–214, 2014 Furosemide – phototoxic blisters BJD 94:495–499, 1976 Gemcitabine – bullous reactions JAAD 71:203–214, 2014 Gliptin-induced bullous pemphigoid JAMADerm 155:147–148, 2019 Heparin-induced skin necrosis – black necrotic bullae of the abdomen JAAD 71:1033–1035, 2014

Heparin-induced thrombocytopenia – personal observation Ibuprofen-induced bullous pemphigoid JAAD 19:91–94, 1988 IL-2 reaction AD 130:890–893, 1994 Infliximab – bullous cutaneous eruption Arthritis Rheum 46:2257– 2258, 2002 Iododerma – vesicular JAAD 36:1014–1016, 1997; bullous Australas J Dermatol 28:119–122, 1987 Immune checkpoint inhibitors – CTLA-4, PD-1/PD-L1 inhibitors – bullous pemphigoid Clin in Dermatol 38:94–104, 2020 Jarisch-Herxheimer reaction – vesicular; treatment of syphilis, onchocerciasis, Lyme disease, strongyloidiasis AD 125:77–81, 1989; Hautarzt 35:588–590, 1984 Leukocytoclastic vasculitis – ibuprofen – personal observation Leuprolide – dermatitis herpetiformis Cutis 75:49–52, 2005 Linagliptin (2-peptidyl peptidase 4 (DPP-4) inhibitors – bullous pemphigoid BJD 176:541–543, 2017; JAMADerm 152:224–226, 2016 Linear IgA disease  Drug-induced JAAD 42:316–323, 2000; JAAD 32:296, 1995   Acetaminophen JAAD 48:289–300, 2003   Amiodarone JAAD 31:809–811, 1994   Ampicillin   Atorvastatin JAAD 44:696–699, 2001   Captopril Cutis 44:393–396, 1989; JAAD 38:352–356, 1998   Carbamazepine JAAD 46:S32–33, 2002    Cefamandole JAAD 48:289–300, 2003; JAAD 38:352–356, 1998   Cyclosporine JAAD 42:316–323, 2000   Diclofenac JAAD 26:45–48, 1992; AD 124:1186–1188, 1988   Glibenclamide AD 123:1121–1122, 1987    Interferon alpha, gamma JAAD 42:316–323, 2000   Interleukin-2    Iodine contrast agent    Lithium carbonate AD 124:1186–1188, 1988; JAAD 26:45–48, 1992    Penicillin G potassium JAAD 42:316–323, 2000   Phenytoin JAAD 38:352–356, 1998   Polychemotherapy JAAD 38:352–356, 1998   PUVA   Somatostatin JAAD 38:352–356, 1998   Sulfisoxazole JAAD 38:352–356, 1998   Vancomycin AD 147:1443–1448, 2011; JAAD 26:45–48, 1992; mimicking TEN JAAD 48:556–557, 2003   Vigabatrin JAAD 42:316–323, 2000 Lupus erythematosus   Drug-induced subacute cutaneous lupus erythematosus   Malar rash   Bullous lesions    Vasculitic lesions of the legs    Crusted and necrotic annular and polycyclic lesions Methimazole-induced vasculitis – vesiculobullous lesions Acta DV 82:206–208, 2002; eschar-like leg ulcers JAMADerm 153:223–224, 2017 Methotrexate – photorecall of Stevens-Johnson syndrome BJD 166:1145–1146, 2012 Methotrexate and leucovorin (palms and soles) AD 123:990–992, 1987 Nalidixic acid – UVA; bullous photoreaction Am J Med 58:576–580, 1975 Nilotinib – bullous Sweet’s syndrome in chronic myelogenous leukemia treated with tyrosine kinase inhibitor nilotinib AD 144:361– 364, 2008

Bullae and/or Vesicles Nivolumab – lichen planus pemphigoides; bullae, erosions, red plaques Cutis 103:224–226, 2019

   Thermal burns    Tincture of benzoin

Oka strain varicella – in immunocompromised patient; vesicular eruption AD 142:943–945, 2006

Pemetrexed – bullous reactions JAAD 71:203–214, 2014

Pegfilgrastim – giant bullae; bullous Sweet’s syndrome due to pegfilgrastim (pegylated G-CSF) JAAD 52:901–905, 2005 Pemphigus vegetans due to captopril JAAD 27:281–284, 1992 Pemphigus – drug-induced – captopril, sulfasalazine, d-penicillamine, bucillamine, Cetapril, thioprinine BJD 171:544–553, 2014; JAAD 39:876–878, 1998; JAAD 26:364–366, 1992; JAAD 30:651– 653, 1994  Antibiotics   Ampicillin   Cephalexin   Cefadroxil   Ceftazidime   Ethambutol   INH   Nalidixic acid   Penicillin   Rifampin   Pyrazalon derivatives   Aminophenazone   Aminopyrine   Azapropazone   Oxyphenbutazone   Phenylbutazone   Sulfur-containing drugs   5-Thiopyridoxine   Captopril   Enalapril   Gold (aurothioglucose)   Mercaptopropionylglycine   Penicillamine   Pyritinol   Sulfasalazine   Tetanus and diphtheria vaccine with a thiol preservative BJD 147:188–189, 2002   Thiamazole   Thiopronine  Miscellaneous   Aspirin   Benzoin   Echinacea JAAD 53:S105–107, 2005   5-Fluorouracil (topical)   Furosemide   Glibenclamide   Heroin   Hydantoin   Ibuprofen   Indomethacin    IL-2 and beta-interferon   Levodopa   Lysine acetylsalicylate   Meprobamate   Nifedipine   Phenacetin   Phenobarbital   Phenylbutene   Piroxicam   Practolol   Progesterone   Propranolol   Pyritinol   PUVA   Spirulina platensis JAAD 53:S105–107, 2005

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Penicillamine AD 128:977–982, 1992; penicillamine-induced pemphigus vulgaris or foliaceus JAAD 37:121–123, 1997; AD 128:977–981, 1992; JAAD 6:317–324, 1982; Am J Dermatopathol 3:85–92, 1981; bullous pemphigoid-like eruption AD 123:1119– 1120, 1987; JAAD 8:548–550, 1983; EBA-like bullae in chronic GVHD disease JAAD 49:1157–1159, 2003 Penicillin-induced bullous pemphigoid mimicking erythema multiforme JAAD 18:345–349, 1988 Phenacetin-induced bullous pemphigoid-like eruption AD 120:1196– 1199, 1984 Phlebogram dye – toxic reaction Piroxicam photodermatitis PPD reaction Pseudoporphyria cutanea tarda JAAD 44:100–108, 2001; JAAD 33:551–573, 1995; JAAD 31:500, 1994  Drug-induced   Acitretin JAAD 53:169–171, 2005   Amiodarone    B complex vitamins   Benoxaprofen   Bumetanide JAAD 23:129–130, 1990   Carisoprodol/aspirin   Chlorthalidone JAAD 21:1026–1029, 1989    Ciprofloxacin – personal observation   Coca-Cola JAAD 44:100–108, 2001   Cyclosporine AD 139:1373–1374, 2003   Dapsone   Diflunisal   Erythropoietin   Etretinate   Finasteride AD 147:747–748, 2011   Fluoroquinolones   5-Fluorouracil   Flutamide   Furosemide Acta Med Scand 202:61–64, 1977   Hydrochlorothiazide/triamterene   Isotretinoin   Ketoprofen   Mefenamic acid   Metformin J Drugs in Dermatol 11:1272, 2012    Nabumetone BJD 142:1067–1069, 2000; BJD 138:549–5500, 1998   Nalidixic acid JID 82:210–213, 1984   Naproxen AD 122:451–454, 1986   Piroxicam   Rofecoxib (Vioxx) JAAD 50:647–648, 2004   Oxaprozin   PUVA   Pyridoxine (vitamin B6) JAAD 14:915–917, 1986; JAAD 10:527–528, 1984   SOMA   Sulfonamides   Sulfonylureas   Tetracycline Clin Exp Dermatol 5:321–325, 1980    Toxic epidermal necrolysis JAAD 69:173–184, 2013    Tiaprofenic acid   Vemurafenib and radiation recall dermatitis JAMADerm 149:855–857, 2013   Voriconazole Photodermatol Photoimmunol Photomed 23:29–31, 2007; JAAD 53:341–345, 2005; Int J Dermatol 43:768–771, 2004 PUVA Cutis 41:199–202, 1988; AD 123:1471–1477, 1987

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Sertraline – giant bulla with necrosis BJD 150:164–166, 2004

Tanning bed AD 125:1236–1237, 1989

Sorafenib (multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of the feet, hyperkeratotic plaque or blister of the feet, red patches on pressure points, red swollen fingertips, gray blisters of the fingerwebs, angular cheilitis, perianal dermatitis BJD 161:1045–1051, 2009; BJD 158:592–596, 2008; bullae of the soles Ped Derm 26:349–350, 2009

Woods Contact Dermatitis 19:224–225, 1988

Sunitinib – multikinase inhibitor; bullous palmoplantar erythrodysesthesia, periungual erythema, perianal erythema, mucositis BJD 161:1045–1051, 2009; AD 144:123–124, 2008 Tiopronin Ann DV 117:9, 1990 Toxic epidermal necrolysis – multiple drugs Ped Derm 36:548–551, 2019  Vaccines – hantavirus, measles virus, MMR vaccine, meningococcal type B, varicella, yellow fever  Over-the-counter medications – acetaminophen, dimenhydrinate, cold medications, ascorbic acid, Ayurvedic drugs, Chinese herbs  Unusual medications – benzodiazepines, albuterol, chemotherapy, d-penicillamine, birth control pills, warfarin  Exogenous agents – insecticides, lambda cyhalothrin, thiamethoxam  Immune dysregulation – bone marrow transplant, graft vs. host disease, linear IgA disease, systemic lupus erythematosus, toxic shock syndrome Toxic erythema of chemotherapy – erythema of the hands and feet with giant bullae Clin in Dermatol 29:587–601, 2011   Cytosine arabinoside   Doxorubicin and other anthracyclines  5-Fluorouracil  Capecitabine   Docetaxel and other taxanes  Methotrexate Trimethoprim – bullous fixed drug eruption; bulla of the leg with surrounding erythema AD 143:535–540, 2007 Vemurafenib – toxic epidermal necrolysis BJD 174:621–624, 2016; BJD 172:1454–1455, 2015 Vasopressin, intravenous JAAD 15:393–398, 1988 Voriconazole – photodermatitis with acute and chronic changes of sun damage JAAD 52:S81–85, 2005; voriconazole in graft vs. host disease – giant bullae of the hands, feet, and legs which progress to necrosis JAAD 58:484–487, 2008; pseudoporphyria Photodermatol Photoimmunol Photomed 23:29–31, 2007; JAAD 53:341–345, 2005; Int J Dermatol 43:768–771, 2004

EXOGENOUS AGENTS Acute iododerma – radiocontrast material; personal observation Buttercup (Ranunculus sp.) Cutis 69:171–172, 2002 Garlic burns Ped Derm 17:475–476, 2000 Hydrogen peroxide – air- and fluid-filled blebs (oxygen bubbles) due to occupational skin injury Dermatology 201:61–64, 2000 Irritant contact dermatitis Clin Dermatol 38:176–192, 2020; plant irritant contact dermatitis, vesiculobullous – buttercup, spurge, manzanillo tree, milfoil, mayweed; Malva Neglecta Wallr Dermatitis 25:140–146, 2014

INFECTIONS AND INFESTATIONS Acinetobacter baumannii – edematous cellulitis with small vesicles and hemorrhagic bullae after war trauma Clin Infect Dis 47:444– 449, 2008; cellulitis with overlying vesicles progress to necrotizing fasciitis with bullae Surg Infect (Larchmt) 11:49–57, 2010 African tick-bite fever (Rickettsia africae) – hemorrhagic pustule, purpuric papules; transmitted by Amblyomma ticks – high fever, arthralgia, myalgia, fatigue, rash in 2–3 days, with eschar, maculopapules, vesicles, and pustules Clin Inf Dis 39:700–701, 741–742, 2004; JAAD 48:S18–19, 2003 Anthrax – Bacillus anthracis; malignant pustule; face, neck, hands, arms; starts as papule, then evolves into bulla on red base; then hemorrhagic crust with edema and erythema with small vesicles; edema of surrounding skin Am J Dermatopathol 19:79–82, 1997; Br J Ophthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981; intravenous drug abuse – edema, necrosis, bullae, compartment syndrome, necrotizing fasciitis Clin Inf Dis 61:1840–1849, 2015 Aspergillosis – primary cutaneous Bacillus cereus – cutaneous infection begins with vesicle and/or pustule and becomes cellulitis; then a nonhealing ulcer with a black eschar JAMADerm 153:1047–1048, 2017; Cutis 79:371–377, 2007; Lancet Mar 18;1(8638):601–603, 1989; necrotic bullae AD 127:543– 546, 1991 Bacteroides – synergistic necrotizing cellulitis Bedbugs – bullae of the face and legs Ped Derm 26:747–748,2009 Beetles – whiplash dermatitis – linear blisters JAAD 22:815–819, 1990; Paederus beetle – vesicular and bullous reactions Cutis 69:277–279, 2002; blister beetles Cutis 104:317–319, 2019 Benign acral papulovesicular eruptions following smallpox vaccination (ACAM 2000); pruritic painful papulovesicular and vesiculopustular and/or bullous eruptions over extensor areas, palms and soles, dorsal hands and feet on days 10–18; generalized vaccinia AD 146:656–661, 2010 Blister beetle dermatosis (Lytta vesicatoria) Ped Derm 9:246–250, 1992; JAAD 22:815–819, 1990; rove beetles (Paederus species) AD 94:175–185, 1966; coconut; Epicauta JAAD 67:331–344, 2012 Blistering distal dactylitis Brown recluse spider bite – blister with purpuric base Clin Inf Dis 32:595,636–637, 2001; small vesicle JAAD 55:888–890, 2006 Brucellosis – vesicular eruptions Cutis 63:25–27, 1999; AD 117:40–42, 1981 Campylobacter jejuni – small vesicles in X-linked agammaglobulinemia J Clin Inf Dis 23:526–531, 1996 Candidiasis – sepsis Med 64:115–133, 1985; congenital cutaneous candidiasis – bullae, maculovesicular eruption JAAD 37:817–823, 1997; AJDC 135:273–275, 1981; Candida kefyr – unilateral red nodules of the leg, bullae, pustules; arterial thrombus of the left iliac artery Cutis 91:137–140, 2013 Caterpillar bites – saddleback caterpillar (Limacodidae) (Acharia stimulea) – urticaria or vesicles; painful sting JAAD 62:1–10, 2010 Cat scratch disease – inoculation vesicle Ped Derm 5:1–9, 1988

Intravenous infiltration

Cellulitis, bullous JAAD 67:163–174, 2012

Intravenous infiltration with compartment syndrome AD 140:798– 800, 2004

Cheyletiella blakei mite dermatitis Cutis 99:335–336, 2017; Ann DV 127:826–829, 2000; JAAD 37:265–266, 1997

Rhus – ingestion of Rhus as folk medicine remedy BJD 142:937– 942, 2000

Chikungunya fever Ped Derm 35:408–409, 2018 Chromobacterium violaceum – vesicles JAAD 54:S224–228, 2006

Bullae and/or Vesicles Chrysaora plocamia (“true jellyfish”) – widespread erythema with bullae JAAD 61:733–750, 2009 Clostridial cellulitis

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Erythema (chronicum) migrans – Borrelia burgdorferi; Lyme disease Am J Med 99:412–419, 1995; vesicular form with secondary necrosis JAAD 49:363–392, 2003; Science 216:1317–1319, 1982

Clostridial myonecrosis (gas gangrene) – C. perfringens, septicum, novyi, or haemolyticum JAAD 6:289–299,1982

Escherichia coli sepsis – bullous cellulitis

Corals (true corals) (Anthozoa) – erythema, bullae, ulcers JAAD 61:733–750, 2009

Fire ant stings (Solenopsis invicta) – clusters of vesicles evolve into umbilicated pustules on red swollen base; crusting, heal with scars; urticaria J S C Med Assoc 95:231–235, 1999; Ann Allergy Asthma Immunol 77:87–95, 1996; Allergy 50:535–544, 1995; Ped Derm 9:44–48, 1992

Covid-19 infection – varicella-like exanthem JAAD 83:280–285, 2020 Cowpox (Orthopoxvirus infection) – cropping of vesicles; resembles orf, anthrax, and impetigo (papulovesiculopustule) – targetoid and umbilicated indurated papules, vesicles, pustules with central necrosis; exposure to pet rat Clin Inf Dis 68:1063–1064, 2019; BJD 153:451–453, 2005; JAAD 49:513–518, 2003; JAAD 44:1–14, 2001; JAAD 42:892–894, 2000; generalized cowpox in Darier’s disease – crusted papules, pustules, and vesicles; cobblestoned appearance; with massive periorbital edema BJD 164:1116–1118, 2011 Coxsackie A (5, 9, 10, 16) – hand, foot, mouth disease; maculopapular-­vesicular; Coxsackie A4 – widespread vesicular eruption Pediatrics 41:873–882, 1968; Coxsackie A6 – generalized vesicular exanthema with flexural vesicles; acral purpuric macules of the palms and soles Ped Derm 33:429–437, 2016 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of the fingers, palmar erythema, red papules of the ears, red papules of the antecubital fossa, perioral papulovesicles, vesicles of the posterior pharynx; crusted papules of the scalp, ears, and face; purpuric targetoid painful vesicular lesions of the hands and feet, arthritis, fissured scrotum; headache, arthralgias JAMADerm 153:219–220, 2017; J Clin Virol 60:381–386, 2014; J Clin Virol 59:201–203, 2014; JAMADerm 149:1419–1421, 2013; JAAD 69:736–741, 2013; MMWR 61:213–214, 2012 Cryptococcosis – vesicles and bullae; may simulate herpes simplex or varicella-zoster virus infection AD 112:1734–1740, 1976 Cutaneous larva migrans Cytomegalovirus infection JAAD 18:1330–1338, 1988; JAAD 12:720–721, 1985; vesiculobullous lesions Dermatology 200:189–195, 2000; JAAD 38:349–351, 1998; JAAD 11:743–747, 1984; pustules, ulcers, bullae, and vesicles in fatal CMV AD 127:396–398, 1991 Diphtheria, cutaneous – painful vesicle evolving into pustule, then anesthetic shallow punched-out ulcer with gray-black membrane Cutis 79:371–377, 2007; heel ulcerations, bullae; fatal heart block Ped Cardiol 21:282–283, 2000; J Med Assoc Thai 56:670–674, 1973 Dracunculosis – small papule or vesicle which ruptures Dermatol Clinic 7:323–330, 1989; Dracunculus medinensis (Guinea worm) – stagnant water with copepods; painful popular lesions, nausea and vomiting, fever, syncope, urticarial, red papulonodular lesions which become vesiculobullous, cellulitis lesions JAAD 73:929–944, 2015 Echovirus 4, 9, 11 – morbilliform, vesicular; Echovirus 11 – vesicular rash AD 113:1705–1706, 1977 Eczema vaccinatum – smallpox vaccination; vesicles, pustules, swollen face with vesicles and eschar (progressive vaccinia, vaccinia necrosum, vaccinia gangrenosum) in patients with cell-mediated immune defects Cutis 101:87–90, 2018 Ehrlichiosis – human monocytic ehrlichiosis; macular and papular erosions, petechiae, edema, vesicles, purpuric plaques JAAD 75:1–16, 2016; JAAD 49:363–392, 2003 Enterobacter cloacae JAAD 27:637–638, 1992 Enteroviral infection – vesicular lesions in AIDS Erysipelas – bullous cellulitis; bullous erysipelas Ped Derm 28:189–190, 2011

Exanthem subitum with vesicular lesions BJD 132:614–616, 1995

Fire corals(Millepora spp.) – urticarial lesions followed by vesiculobullous rash, chronic granulomatous and lichenoid lesions; scuba divers; hemorrhagic bullae, necrosis, ulceration, urticarial JAAD 61:733–750, 2009; Contact Dermatitis 29:285–286, 1993; Int J Dermatol 30:271–273, 1991 Foot and mouth disease (Echovirus) – adults and children in direct contact with infected livestock; vesicles of the buccal mucosa, tongue, lips, palms, soles, interdigital skin Br Med J 4:529–530, 1967 Fournier’s gangrene Fusarium sepsis – F. falciforme – red plaques, vesicles, pustules, necrosis BJD 157:407–409, 2007 Glanders – Pseudomonas mallei – cellulitis which ulcerates with purulent foul-smelling discharge, regional lymphatics become abscesses; nasal and palatal necrosis and destruction; metastatic papules, pustules, bullae over joints and face, then ulcerate; deep abscesses with sinus tracts occur; polyarthritis, meningitis, pneumonia Gonococcemia – periarticular lesions appear in crops with red macules, papules, vesicles with red halo, pustules, bullae becoming hemorrhagic and necrotic; suppurative arthritis and tenosynovitis Ann Int Med 102:229–243, 1985 Gram-negative web space infection Herpangina – Coxsackie A1, A6, A10, A22, B1–5, Echovirus types 9, 11, 17 Prog Med Virol 24:114–157, 1978; oral vesicles Herpes B infection – Macaque monkey bite; herpes simplex-like lesions with vesicles, erythema, and edema near bite site; secondary vesiculopapular eruption JAAD 49:979–1000, 2003; AD 125:1247–1248, 1989 Herpes simplex – primary; neonatal, HIV, disseminated, eczema herpeticum; palmar and plantar bullae in infancy Ped Derm 15:108–111, 1998; AD 114:406, 1978; herpetic whitlow; dyshidrosislike herpes simplex in AIDS JAAD 13:845–852, 1985; eczema herpeticum (Kaposi’s varicelliform eruption) Rook p. 1028, 1998, Sixth Edition; Arch Dis Child 60:338–343, 1985; oral vesicles Herpes zoster – dermatomal grouped vesicles on erythematous base; purpuric, umbilicated, necrotic bullae of the leg AD 147:235– 240, 2011; satellite lesions in herpes zoster BJD 172:1530–1534, 2015 Histoplasmosis, disseminated – vesicular lesions AD 143:255–260, 2007 Impetigo, bullous – staphylococcal; bullae and crusts Curr Prob Dermatol 5:196–204, 1993; non-bullous (streptococcal) – thinwalled vesicle on red base ruptures and crusts; palmar and plantar bullae in infancy Ped Derm 15:108–111, 1998; Br Med J 1:467–469, 1864 Infectious mononucleosis – vesicular and bullous exanthems Tyring, p. 149, 2002 Insect bite reaction – papules with overlying vesicle Rook pp. 1425– 1426, 1998, Sixth Edition; bullae in children, associated with CLL Acta DV (Stockh) 57:81–92, 1977; natural killer cell lymphocytosis AD 126:362–368, 1990; HIV disease JAAD 29:269–272, 1993;

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fleas, mosquitoes, gnats, midges, flies, mites, bugs, beetles, thrips (thunder flies); Haematosiphoniasis (Mexican chicken bug) – wheals, papules, vesicles, pustules, crusts; mites – barley itch, grain-shoveller’s itch, grain itch, straw itch, cotton seed dermatitis; beetles (Paederus fuscipes) – blisters, papules Eur J Ped 152:6–8, 1993; bedbugs (Cimex lectularius, C. hemipterus) The Clinical Management of Itching; Parthenon; p. 63, 2000; sandflies (Phlebotomus, Lutzomyia) – harara, urticaria multiformis endemica in the Middle East The Clinical Management of Itching; Parthenon; p. 64, 2000 Jellyfish stings – “true jellyfish” (Chrysaora plocamia) – widespread erythema with bullae JAAD 61:733–750M 2009 Leprosy – Lucio’s phenomenon AD 114:1023–1028, 1978; erythema nodosum leprosum JAAD 51:416–426, 2004; AD 132:1432–1434, 1996

Omsk hemorrhagic fever virus – infected muskrats in western Siberia; papulovesicular lesions of the soft palate AD 140:656, 2004 Onchocerciasis (Onchocerca volvulus) – acute papular onchodermatitis – papules, vesicles, pustules JAAD 73:929–944, 2015 Orf – vesicopapule – palmar bulla JAMA 308:126–128, 2012; JAAD 44:1–14, 2001; generalized severe blistering eruptions (bullous orf) JAAD 58:49–55, 2008; Int J Derm 6:340–341, 1980; AD 126:356– 358, 1990 Zoonotic orthopoxvirus – teats of cows as source; targetoid bullae of the hands and fingers healing with eschars; edema of the hands; fever; axillary lymphadenopathy NEJM 372:223–230, 2015 Otitis externa Ann Otol Rhinol Laryngol 82(Suppl 8):1–23, 1973 Paecilomyces lilacinus – vesicular lesions JAAD 39:401–409, 1998; papulovesicular lesions Ann Int Med 125:799–806, 1996

Listeria monocytogenes – contact listeriosis; localized vesicles or pustules JAAD 48:759, 2003

Paederus beetle dermatitis – linear papular, vesicular, and pustular dermatitis JAAD 57:297–300, 2007; Cutis 69:277–279, 2002

Marburg virus – maculopapular-vesicular

Parvovirus B19 – bullous papular-purpuric gloves and socks syndrome JAAD 60691–695, 2009

Measles – with extensive bullous eruption NEJM 277:248–250, 1967 Meningococcemia Milker’s nodule – vesicopapule JAAD 44:1–14, 2001 Millipede secretions – conjunctivitis and mahogany pigmentation with bullae Cutis 67:452, 2001 Mites – cheese mite (Glyciphagus) bites – papulovesicles and pustules Dermatol Clin 8:265–275, 1990 Monkeypox – exanthem indistinguishable from smallpox (papulovesiculopustular) (vesicles, umbilicated pustules, crusts) but is centrifugal; fever, chills, headache, back pain, sore throat, myalgias, diaphoresis, cough, nausea, vomiting, nasal congestion, blepharitis, oral ulcers, centrifugally clustered umbilicated papules and pustules, lymphadenopathy; heal with varioliform scarring JAMA 304:1659, 2010; JAAD 55:478–481, 2006; JAAD 55:478–481, 2006; NEJM 355:962–963, 2006; CDC Health Advisory, June 7,2003; JAAD 44:1–14, 2001; J Infect Dis 156:293–298, 1987; Bull World Health Organ 46:593–597, 1972 Morganella morganii JAAD 12:575–576, 1985 Mosquito bite hypersensitivity syndrome in EBV-associated natural killer cell leukemia/lymphoma – clear or hemorrhagic bullae with necrosis, ulceration, and scar formation JAAD 45:569–578, 2001 Mucormycosis – vesicles; Mucor, Rhizopus oryzae, Rhizomucor, Lichtheimia, Saksenaea, Cunninghamella, Apophysomyces pink papules JAAD 80:869–880, 2019; Med 64:115–133, 1985; zygomycosis – annular bullae with central necrosis Ped Derm 24:257–262, 2007 Mycobacterium tuberculosis – miliary tuberculosis; large crops of blue papules, vesicles, pustules, hemorrhagic papules; red nodules; vesicles become necrotic to form ulcers Practitioner 222:390–393, 1979; Am J Med 56:459–505, 1974; AD 99:64–69, 1969 Mycoplasma pneumoniae – varicella-like rash Am J Dis Child 128:254–256, 1974 Necrotizing fasciitis – necrotic bullae; streptococcal Curr Prob in Dermatol 14:183–220, 2002; Ann DV 128:376–381, 2001; Serratia marcescens Clin Inf Dis 23:648–649, 1996; JAAD 20:774–778, 1989; Bacteroides spp. in penile necrotizing fasciitis JAAD 37:1–24, 1997; neonatal Pediatrics 103:e53, 1999; in infancy Ped Derm 2:55–63, 1984; Clostridial cellulitis (gangrene); progressive synergistic gangrene; gangrenous cellulitis (Pseudomonas); Fournier’s gangrene Nocardia asteroides AD 121:898–890, 1985 Non-clostridial crepitant cellulitis Non-clostridial myositis

Pediculid, bullous Cutis 41:281, 1988 Pediculosis – pubic lice (Phthirus pubis) Arch Dermatol Syphilol 65:334–339, 1952 Phaeohyphomycosis JAAD 40:364–366, 1999 Phycomycotic gangrenous cellulitis Portuguese man-of-war stings – vesicular J Emerg Med 10:71–77, 1992 Progressive bacterial synergistic gangrene – postoperative (Meleney’s synergistic gangrene) Protothecosis – vesiculobullous lesions Med 64:115–133, 1985; JAAD 32:758–764, 1995 Pseudoflavobacterium sepsis – personal observation Pseudomonas sepsis – bullae which rupture to yield necrotic ulcers (ecthyma gangrenosum) Medicine 64:115–133, 1985; Ped Derm 4:18–20, 1987; red nodules with bullae atop Ped Derm 28:204–205, 2011 Puss caterpillar – purpuric papulovesicles Cutis 60:125–126, 1997 Q fever – Coxiella burnetii; vesicles JAAD 49:363–392, 2003 Rat-bite fever (Streptobacillus moniliformis (pleomorphic facultative anaerobic bacillus) or Spirillum minor (sodoku)) – macular, petechial, or morbilliform widespread exanthem; palmoplantar rash; arthralgia and chronic arthritis; Haverhill fever (raw milk) – papules, crusted papules, vesicles, papulovesicles, pustules; chronic abscesses Clin Infect Dis 43:1585–1586,1616–1617, 2006; Cleveland Clin Q 52(2):203–205, 1985; Pediatr Clin N Am 26:377– 411, 1979 Rickettsia australis; R. conorii – varicelliform rash – papulovesicular Rickettsialpox (Rickettsia akari) (house mouse mite bite) – fever with generalized papules, vesicles, papulovesicles, crusts with ulceronecrotic plaque Ped Derm: 29:767–768, 2012; NEJM 331:1612–1617, 1994; Clin Inf Dis 18:624–626, 1994 Rickettsia australis (tick typhus) – papulovesicular Clin Inf Dis 18:118–119, 1994 Rickettsia parkeri rickettsiosis – Gulf coast tick (Amblyomma maculatum); eschar with surrounding petechiae, fever, fatigue, headache, myalgia, arthralgia, morbilliform or vesiculopapular rash of the trunk and extremities, palms and soles, and occasionally the face; some lesions with small vesicle or pustule MMWR 65:1–44, May 13, 2016; Clin Inf Dis 47:1188–1196, 2008 Roseola infantum (human herpesvirus 6) – rose-pink macules start on the neck and trunk, then spread to the face and extremities; rarely vesicular BJD 132:614–616, 1995

Bullae and/or Vesicles Salmonella – vesicular eruptions NYS J Med 81:1639–1641, 1981 Scabies with bullous pemphigoid-like eruption (bullous scabies) JAAD 82:533–548, 2020; Ped Derm 36:552–553, 2019; Cutis 350–352, 2008; J Dermatol 30:694–696, 2003; JAAD 20:878–879, 1996; J Dermatol 33:196–201, 2006; JAAD 24:179–181, 1991; vesicles and bullae JAAD 20:134–136, 1989; palmar bullae JAAD 49:346–350, 2003; palmar and plantar bullae in infancy Ped Derm 15:108–111, 1998; JAMA 230:878, 1974; generalized papulovesicular eruption JAMA 321:604–605, 2019

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Tropical ulcer (phagedenic ulcer) – mixed infection with Fusobacterium ulcerans and other organisms; papule or bulla which breaks down to form ulcer with undermined border Int J Dermatol 27:49–53, 1988 Tularemia – vesiculopapular lesions of the trunk and extremities Photodermatology 2:122–123, 1985 Vaccinia – Jennerian vesicle; papulovesiculopustule JAAD 44:1–14, 2001; progressive vaccinia – cellulitis with bullae J Clin Inf Dis 25:911–914, 1997

Sea anemones – erythema, bullae, ulcers JAAD 61:733–750, 2009

Varicella – vesicular JAAD 9:209–212, 1983; oral vesicles; reinfection varicella Clin Inf Dis 52:907–909, 2011

Sealpox (Parapoxvirus) – gray concentric nodule with superimposed bulla on the dorsum of the hand BJD 152:791–793, 2005

Variola – papulovesiculopustule

Serratia marcescens – bullous cellulitis due to iguana bite JAAD 62:1075–1076, 2010 Smallpox – varicella-like JAAD 44:1–14, 2001; smallpox vaccination site; macular and papular exanthems of the face and extremities develop vesicles, pustules, and umbilicated crusts; hemorrhagic smallpox more severe; flat smallpox with sloughing blisters JAAD 65:1213–1218, 2011 Snake bites – edema, erythema, pain, bullae, ecchymosis, and necrosis NEJM 347:347–356, 2002 Spider bites Trans R Soc Trop Med Hyg 92:546–548, 1998; South Med J 69:887–891, 1976; brown recluse spider bite JAAD 44:561– 573, 2001 Staphylococcal cellulitis – personal observation Staphylococcal scalded skin syndrome – erythroderma, bullae, erosions BJD 166:213–215, 2012; toxic epidermal necrolysis JAAD 59:342–346, 2008; Zentralseit Kinderheilkd 2:3–23, 1878 Staphylococcal sepsis (MRSA) – diffuse umbilicated vesicles JAMADerm 149:641–642, 2013 Stink bugs (Pentatomidae) – red plaques and vesicles JAAD 67:331–344, 2012 Straw itch mites – varicella-like JAMA 247:1821, 1982 Streptococcus, Group B – resembles bullous impetigo Streptococcal gangrene (necrotizing fasciitis) JAAD 20:774–778, 1989 Group G streptococcal myositis with toxic shock syndrome Clin Inf Dis 23:1159–1161, 1996 Streptococcal toxic shock syndrome – painful localized edema and erythema; progression to vesicles and bullae Textbook of Neonatal Dermatology, p. 189, 2001 Syphilis, congenital – targetoid erythema multiforme-like lesions JAAD 55:S11–15, 2006; BJD 149:658–660, 2003; vesicular Jarisch-Herxheimer reaction AD 125:77–81, 1989; papulovesicular lesions in AIDS JAAD 22:1061–1067, 1990 Tick bite – soft ticks; argasid ticks Lancet ii:288–289, 1982; Ornithodorus JAAD 49:363–392, 2003 Tinea corporis, pedis – bullous, Trichophyton mentagrophytes – annular bullae JAAD 55:153–154, 2006; Nature Genet 17:241–244, 1997 Toxic shock syndrome, either streptococcal or staphylococcal – widespread macular erythema, scarlatiniform, and papulopustular eruptions; occasional vesicles and bullae; edema of the hands and feet; mucosal erythema; second week morbilliform or urticarial eruption occurs with desquamation at 10–21 days JAAD 39:383–398, 1998; Rev Infect Dis 11(Suppl 1):S1–7, 1989; JAAD 8:343–347, 1983 Toxoplasmosis Trichophyton tonsurans – concentric bullae AD 145:497, 2009 Trichosporon beigelii AD 129:1020–1023, 1993

Vesicular stomatitis virus – vesicles of the fingers, gums, buccal, and pharyngeal mucosa NEJM 277:989–994, 1967 Vibrio vulnificus Clin Inf Dis 40:718,754–755, 2005 Yersinia enterocolitica – vesicles J Clin Inf Dis 21:223–224, 1995 Yersinia pestis (plague) – umbilicated vesicles or pustules J Infect Dis 129:S78–84, 1974

INFILTRATIVE DISEASES Amyloidosis, bullous – flaccid bullae JAAD 71:1035–1037, 2014; AD 144:673–678, 2008; JAAD 54:712–714, 2006; Medicine 24:124– 128, 1994; Cutis 43:346–352, 1989; BJD 113:85–95, 1985; AD 117:782–784, 1981; oral bullae Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:734–740, 2006; lichen amyloidosis Ann Acad Med Singapore 29:105–107, 1990 Congenital self-healing reticulohistiocytosis – papulovesicular lesions Ped Derm 18:35–37, 2001; AD 134:625–630, 1998 Langerhans cell histiocytosis – purpuric vesicles JAAD 37:314–317, 1997; palmar and plantar bullae in infancy Ped Derm 15:108–111, 1998; vesiculopapules AD 127:1049–1054, 1991; Langerhans cell histiocytosis – vulvar vesicles Obstet Gynecol 67:46–49, 1986; umbilicated blisters and pustules Hematol Oncol Clin North Amer 12:269–286, 1998 Mastocytosis, bullous – urticaria pigmentosa Clin Exp Dermatol 24:16–18, 1999; Cutis 58:358–360, 1996; diffuse cutaneous mastocytosis AD 146:557–562, 2010; AD 144:673–678, 2008; Ped Derm 19:375–381, 2002; xanthelasmoidea BJD 144:355–358, 2001 Nodular eosinophilic infiltration JAAD 24:352–355, 1991 Primary chylous reflux – vulvar vesicles AD 146:683–684, 2010

INFLAMMATORY DISORDERS Edematous scarring vasculitic panniculitis – hydroa vacciniformelike lesions with vesicles, deep ulcers, varicelliform scars JAAD 32:37–44, 1995 Erythema multiforme JAMA 312:426–427, 2014; Medicine 68:133– 140, 1989; JAAD 8:763–765, 1983; palmar and plantar bullae in infancy Ped Derm 15:108–111, 1998; widespread bullae; oral bullae Oral Surg 67:36–40, 1989; Oral Surg 52:257–260, 1981; StevensJohnson syndrome Neutrophilic eccrine hidradenitis J Dermatol 22:137–142, 1995 Pyoderma gangrenosum, bullous BJD 178:595–602, 2018; JAAD 79:1009–1022, 2018; JAAD 27:804–808, 1992; mimicking dermatitis herpetiformis AD 77:269–280, 1958 Sarcoid – vesicular variant Braverman's Skin Signs of Systemic Disease Stevens-Johnson syndrome/toxic epidermal necrolysis BJD 174:1194–1227, 2016

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Toxic epidermal necrolysis BJD 174:1194–1227, 2016; Ped Derm 32:704–709, 2015; BJD 171:1583–1585, 2014; BJD 162:860–865, 2010; JAAD 56:181–200, 2007; BJD 68:355–361, 2005; Oral Maxillofac Surg 40:59–61, 1982; TEN in infancy JAAD 27:341–344, 1992

METABOLIC Acrodermatitis enteropathica or acquired zinc deficiency – infant with vesiculobullous dermatitis of the hands, feet, periorificial areas; periorificial dermatitis, generalized dermatitis, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche JAAD 56:116–124, 2008; Ped Derm 19:426–431, 2002; AD 116:562–564, 1980; Acta DV (Stockh) 17:513–546, 1936; with anorexia nervosa JAMA 288:2655–2656, 2002; bullae of the toes (acquired zinc deficiency) AD 145:829–834, 2009 Anasarca – yellow bullae; personal observation Bullous dermatosis of chronic renal failure – chronic renal failure with or without hemodialysis JAAD 44:100–108, 2001; Ann Int Med 83:480–483, 1975 Calciphylaxis Chylous reflux – white milky blisters JAAD 55:1108–1109, 2006 Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of the fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 167:988–900, 2012 Cryofibrinogenemia –of the dorsal feet Am J Med 116:332–337, 2004 Cryoglobulinemia JAAD 48:311–340, 2003 Diabetic bullae – forearms, hands, fingers, legs, feet, toes Int J Derm 39:196–200, 2000; JAAD 13:799–805, 1985 Gout Ann Rheum Dis 36:91–93, 1977 Hypothyroidism with bullae Miliaria crystallina – vesicles AD 140:231–236, 2004; Cutis 47:103–106, 1991 Necrobiosis lipoidica diabeticorum Paroxysmal nocturnal hemoglobinuria AD 122:1327–1330, 1986 Pellagra Porphyrias – hereditary coproporphyria BJD 96:549–554, 1977; Q J Med 46:229–241, 1977; BJD 84:301–310, 1971; congenital erythropoietic porphyria (Gunther’s disease) – blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, keratoconjunctivitis, cataracts; uroporphyrinogen III synthase deficiency Ped Derm 36:951–952, 2019; BJD 171:422– 423, 2014; JAAD 67:1093–1110, 2012; AD 141: 1575–1579, 2005; Ped Derm 20:498–501, 2003; Semin Liver Dis 2:154–63, 1982; hepatoerythropoietic porphyria AD 138:957–960, 2002; JAAD 11:1103–1111, 1984; porphyria cutanea tarda – vesicles, bullae, crusts, skin fragility, atrophic scars, milia; variegate porphyria – vesicles on the face, neck, dorsal hands; hemorrhagic crusts with increased skin fragility JAAD 2:36–43, 1980; Wien Klin Wochenschr 50:830–831, 1937; BMJ ii:89, 1955; erythropoietic protoporphyria Eur J Pediatr 159:719–725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751–766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976 Pruritic urticarial papules and plaques of pregnancy – vesicles BJD 135:102–105, 1996; JAAD 10:473–480, 1984; Clin Exp Dermatol 7:65–73, 1982; JAMA 241:1696–1699, 1979; bullae of forearms with exanthem BJD 162:220–222, 2010

Pseudoglucagonoma syndrome due to malnutrition – vesicles and bullae at expanding margin AD 141:914–916, 2005 Wilson’s disease – pretibial vesicles with hyperpigmentation JAAD 21:1030–1032, 1989 Zinc deficiency – flaccid bullae of the soles and dorsal feet Cutis 101:450–453, 2018; acquired zinc deficiency from parenteral nutrition – acral erosions and bullae, cheilitis Ped Derm 36:520– 523, 2019

NEOPLASTIC DISEASES Epstein-Barr virus-associated lymphoproliferative lesions – vesicles and papulovesicles BJD 151:372–380, 2004 Kaposi’s sarcoma – in HIV disease Am J Dermatopathol 19:379– 383, 1997 Leukemia cutis Cancer 63:2192–2200, 1989; acute myelomonocytic leukemia; chronic lymphocytic leukemia JAAD 15:943–950, 1986; bullous pyoderma as presentation of acute leukemia Clin Exp Dermatol 2:33–38, 1977; adult T-cell leukemia – bullae of the palms and soles JAAD 46:S137–141, 2002; J Dermatol 19:498–502, 1992; chronic lymphocytic leukemia – vesicular lesions JAAD 58:182–184, 2008; HTLV-1 leukemia/lymphoma with lymphangiectasias – personal observation Lymphatic malformation – circumscribed JAMA 321:1213–1214, 2019 Lymphoma – mycosis fungoides bullosa AD 142:793–795, 2006; BJD 142:124–127, 2000; hand blister BJD 165:213–214, 2011; bullae or papulovesicular lesions of CTCL JAAD 46:325–357, 2002; JAAD 45:934–939, 2001; AD 104:402–406, 1971, Dermatologica 174:34–38, 1987; Dermatologica 148:377–381, 1974; CTCL with malignancy of FOXP3 regulatory cells – bullous lesions; erosive and ulcerative hemorrhagic pyoderma gangrenosum-like lesions JAAD 61:348–355, 2009; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of the ears, fever JAAD 69:112–119, 2013; variant of extranodal NK/T-cell lymphoma, nasal type/CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of the hands, subcutaneous nodules; systemic manifestations; occurs on both sun-exposed and non-sun-­exposed skin Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998 (angiocentric CTCL of childhood (hydroa-like lymphoma) – Latin America and Asia, associated with Epstein-Barr virus JAAD 38:574–579, 1998; AD 133:1081–1086, 1997); adult T-cell lymphoma/leukemia – widespread papulovesicular and bullous eruptions J Drugs in Dermatol 10:1469–1471, 2011; JAAD 46:S137–141, 2002; palmoplantar bullae J Dermatol 19: 498–502, 1992; Hodgkin’s disease Am J Dermatopathol 2:363–366, 1980; chronic T-cell lymphocytic leukemia JAAD 8:874–878, 1983; primary cutaneous anaplastic large cell lymphoma AD 143:255–260, 2007 Lymphomatoid papulosis resembling hydroa vacciniforme JAAD 32:378–381, 1995 Metastatic breast carcinoma – vesicular and zosteriform, mimicking herpes zoster JAAD 43:733–751, 2000; carcinoma telangiectoides – vesicles BJD 151:523–524, 2004; carcinoma erysipelatoides (breast carcinoma) JAAD 40:805–807, 1999 Plasmacytic ulcerative stomatitis (myeloma) – bulla Oral Surg 70:587–589, 1990 Superficial mucoceles Oral Surg 66:318–322, 1988 Syringosquamous metaplasia of the eccrine glands – vesicles JAAD 38:1–17, 1998; AD 123:1202–1204, 1987

Bullae and/or Vesicles Waldenström’s IgM storage papules – skin-colored translucent papules on extensor extremities, buttocks, trunk; may be hemorrhagic, crusted, or umbilicated pruritic papules, vesicles, bullae, urticaria JAAD 45:S202–206, 2001; AD 134:1127–1131, 1998; reticulate purpura and bullae Clin Exp Dermatol 26:513–517, 2001; bullous macroglobulinosis – bullae, scars, erosions, papules of the dorsal hands JAAD 77:1145–1158, 2017 Woringer-Kolopp disease (pagetoid reticulosis) JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939

PARANEOPLASTIC DISEASES Acrokeratosis paraneoplastica (Bazex syndrome) – hand edema, desquamation of the hands; hyperkeratotic and lichenified plaques of the hands; vesicles and bullae of the hands JAMADerm 151:677– 678, 2015; bullae of the hands and feet JAAD 40:822–825, 1999

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Barr virus-related) – red macules progress to tender papules or vesiculopapules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of the cheeks, eyelids, ears, and lips BJD 173:801–805, 2015; AD 142:587–595, 2006; typical and atypical associated with latent EBV infection and lymphoma BJD 140:715–721, 1999 Juvenile spring eruption – vesicular eruption of helices, lips, and cheeks due to Parvovirus B19 JAMADerm 154:1356–1357; bullae JAAD 50:S57–60, 2004 Phytophotodermatitis – confluent erythema with bullae of the upper trunk AD 142:1059–1064, 2006; linear and bullous lesions Rook p. 790, 1998, Sixth Edition; meadow dermatitis (Umbelliferae); lemon, lime, celery, parsnip, figs, carrots, dill, parsley, meadow grass, giant hogweed, wheat, clover, cocklebur, buttercup, shepherd’s purse, pigweed JAAD 67:1093–1110, 2012 Polymorphous light eruption – bullous ear lesions

Bullous pyoderma gangrenosum BJD 178:595–602, 2018; JAAD 79:1009–1022, 2018

Pseudoporphyria cutanea tarda from natural sunlight – personal observation

Bullous Sweet’s syndrome

Solar elastosis, bullous JAAD 34:856–858, 1996

Glucagonoma syndrome – alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; skin rash, angular stomatitis, cheilosis, beefy red glossitis, blepharitis, conjunctivitis, alopecia, crumbling nails; rarely, associated with MEN I or IIA syndromes AD 143:1221–1222, 2007; AD 133:909, 912, 1997; JAAD 24:473–477, 1991; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979

Ultraviolet recall manifested as edema, erythema, bullae, hemorrhagic crusting, macules, papules, ulceration, necrosis JAAD 56:494–499, 2007

Eosinophilic dermatitis associated with hematologic malignancy (hypersensitivity to mosquito bites – associated with lymphoma/ leukemia) BJD 153:210–212, 2005; JAAD 45:569–578, 2001; BJD 138:905–906, 1998 IgA subcorneal pustular dermatosis-like pemphigus with myeloma – superficial blisters and erosions BJD 172:296–298, 2015 Paraneoplastic pemphigus – acral bullae, oral crusts and erosions, cheilitis; associated with non-Hodgkin’s B-cell lymphoma, chronic lymphocytic leukemia, Waldenström’s macroglobulinemia, Hodgkin’s disease, T-cell lymphoma, Castleman’s diseases, thymoma, poorly differentiated sarcoma, round-cell liposarcoma, inflammatory fibrosarcoma, uterine adenosarcoma; autoantibodies to plakin family including plectin, envoplakin, periplakin, desmoplakin I and II, bullous pemphigoid antigen I (BP230) JAAD 80:1544– 1549, 2019; JAMADerm 151:439–440, 2015; JAAD 48:S69–72, 2003; JAAD 40:649–671, 1999; JAAD 39:867–871, 1998; AD 129:866–869, 1993; NEJM 323:1729–1735, 1990; paraneoplastic IgA pemphigus – tense bullae, vesicopustules JAAD 56:S73–76, 2007 Paraneoplastic pemphigus resembling bullous pemphigoid JAAD 43:714–717, 2000; JAAD 29:815–817, 1993; JAAD 40:649–671, 1999; JAAD 39:867–871, 1998; AD 129:866–869, 1993; NEJM 323:1729–1735, 1990; tense bullae of the palms and soles BJD 144:1255–1261, 2001

PRIMARY CUTANEOUS DISEASE Acral peeling – autosomal recessive; acral thin flaccid bullae in infancy; older children get skin peeling; transglutaminase 5 mutation Ped Derm 26:328–330, 2009; JAAD 7:606–613, 1982; AD 3:202, 1921 Acropustulosis of infancy – palmoplantar bullae of infancy Ped Derm 15:108–111, 1998 Acute parapsoriasis (pityriasis lichenoides et varioliformis acuta) (Mucha-Habermann disease) – vesiculopapule AD 123:1335–1339, 1987; AD 118:478, 1982; bullous form JAAD 23:473–478, 1990; febrile ulceronecrotic Mucha-Habermann disease – dusky plaque with bullae Ped Derm 29:135–140, 2012 Anetoderma – bullous appearance of anetoderma overlying a pilomatrixoma JAAD 25:1072–1076, 1991 Angina bullosa hemorrhagica Balanitis xerotica obliterans AD Syphilol 56:613, 1928 Bullous congenital ichthyosiform erythroderma Bullous prurigo pigmentosa – pruritic reticulated bullous eruption of the neck and trunk JAMADerm 150:1005–1006, 2014; Dermatologica Sinica 27:103–110, 2009 Darier’s disease AD 118:278–279, 1982 Delayed pressure urticaria, bullous form – urticarial and bullae BJD 166:1151–1152, 2012 Dyshidrotic eczema, including dyshidrotic id reaction – personal observation Eosinophilic cellulitis BJD 146:160–161, 2002

PHOTODERMATITIS Berloque dermatitis Celery ingestion with phototoxic burn AD 126:1334–1336, 1990 Creosote phototoxic burn Hydroa vacciniforme Clin Exp Dermatol 23:70–72, 1998; AD 122:1310–1313, 1986; AD 114:1193–1196, 1978; crusted vesicles BJD 144:874–877, 2001; associated with latent Epstein-Barr virus infection and lymphoma BJD 140:715–721, 1999; bullae of the ears and hands AD 142:515–520, 2006; hydroa vacciniforme (Epstein-

Epidermolysis bullosa – Third International Consensus Meeting JAAD 70:1103–1126, 2014; JAAD 58:931–950, 2008  Epidermolysis bullosa, lethal acantholytic (suprabasal EBS) – autosomal recessive; desmoplakin mutation   Epidermolysis bullosa simplex with cardiomyopathy – loss of dermatoglyphics, hypohidrosis; mutation in KLHL24 BJD 179:1181–1183, 2018   Epidermolysis bullosa simplex with ectodermal dysplasia and skin fragility – autosomal recessive; plakophilin 1 mutation; palmoplantar keratoderma, woolly hair and alopecia, anhidrosis until first year

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  Epidermolysis bullosa pruriginosa – reticulated linear hypopigmented plaques; bullae; scars; zebra stripe appearance; dyschromatosis Ped Derm 32:549–550, 2015  Epidermolysis bullosa simplex BJD 162:980–989, 2010; plantar bullae BJD 162:1004–1013, 2010; Clin in Dermatol 23:6–14, 2005   Epidermolysis bullosa, autosomal recessive – diffuse palmoplantar keratoderma with pitting, pitted palmoplantar keratoderma, dystrophic toenails, blistering, generalized reticulated hyperpigmentation; dental caries with squamous cell carcinoma of the tongue; keratin 14 mutation; must be differentiated from EBS with mottled pigmentation (keratin 5 mutation), Kindler’s syndrome, Naegeli syndrome – inflammatory blisters and hypohidrosis (keratin 14 mutation), and dyskeratosis congenital (telomerase mutation) BJD 162:880–882, 2010   Epidermolysis bullosa, autosomal recessive – blisters and erosions, mild skin fragility, fatal interstitial lung disease, nephrotic syndrome, sparse fine hair, large dystrophic toenails with distal onycholysis; integrin alpha-B mutation NEJM 366:1508–1514, 2012    EBS, localized – acral blisters, rare oral involvement   EBS, Dowling-Meara – generalized, herpetiform blisters, oral involvement    EBS, associated with muscular dystrophy; plectin mutation    EBS, autosomal recessive   EBS superficialis    EBS, lethal acantholytic   EBS, associated with pyloric stenosis (pyloric atresia) – mutations of integrin beta4 gene J Dermatol Sci 78:61–66, 2015   EBS with mottled pigmentation   Junctional epidermolysis bullosa   JEB, Herlitz   JEB, non-Herlitz    JEB, associated with pyloric atresia  Lethal acantholytic epidermolysis bullosa – universal alopecia, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010  Dominant dystrophic epidermolysis bullosa – bullae and large erosions BJD 172:384–391, 2015   DDEB, generalized    DDEB – bullous dermolysis of the newborn   Recessive dystrophic epidermolysis bullosa    RDEB, severe generalized    RDEB, generalized other    RDEB – bullous dermolysis of the newborn Epidermolysis bullosa pruriginosa – autosomal dominant or autosomal recessive; vesicles, erosions, crusting, hypertrophic scars; dystrophic form of epidermolysis bullosa; mutation in COL7A1 AD 147:956–960, 2011 Epidermolysis bullosa simplex BJD 172:384–391, 2015; Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 89–117; oral bullae with epidermolysis bullosa – simplex – generalized, herpetiform, superficialis AD 125:633–638, 1989; junctional – Herlitz, generalized mild, localized, inverse, progressive; dominant dystrophic – hyperplastic, albopapuloid, and polydysplastic dystrophic type; junctional, non-Herlitz type; COL17A1 mutations (GABEB); enamel hypoplasia BJD 156:861– 870, 2007; recessive dystrophic – localized, generalized, mutilating, inverse Oral Surg 43:859–872, 1977; variants Oral Surg 67:555– 563, 1989; Oral Surg Oral Med Oral Pathol 71:440–446, 1991; late onset junctional epidermolysis bullosa (epidermolysis junctionalis progressiva) – bullae of the hands and feet, nail dystrophy, loss of dermatoglyphic pattern, tooth enamel abnormalities, hyperhidrosis BJD 144:1054–1057, 2001; autosomal recessive epidermolysis bullosa with muscular dystrophy or congenital myasthenia gravis AD 125:931–938, 1989; dominant dystrophic epidermolysis bullosa;

dystrophic epidermolysis bullosa inversa – flexural bullae, oral ulcers, dental caries, milia Ped Derm 20:243–248, 2003; epidermolysis bullosa simplex with mutation of collagen 17A1 gene; ITGB4 coding for integrin beta4 BJD 151:669–674, 2004; JID 118:185–192, 2002   EBS generalized severe type Ped Derm 36:132–138, 2019  EBS of the hands and feet – Weber-Cockayne; acral bullae BJD 159:1370–1372, 2008  EBS with anodontia/hypodontia (Kallin’s syndrome) – thickened or curved nails, alopecia with brittle hair Ghatan, Second Edition, 2002, p. 216  EBS – autosomal recessive – dystonin-e (DYSTe) mutation – large bullae of the dorsal feet BJD 172:527–531, 2015   EBS, generalized – Koebner variant   EBS herpetiformis – Dowling-Meara JAAD 28:859–861, 1993  EBS with mottled pigmentation of the neck, upper trunk, arms, and leg with or without keratoderma (punctate keratoses); cutaneous atrophy, nail dystrophy BJD 128:679–685, 1993; Clin Genet 15:228–238, 1979; acral blistering, hemorrhagic bullae, focal punctate keratoderma, dystrophic thick nails BJD 144:40– 45, 2001  EBS Mendes da Costa variant – X-linked recessive  EBS with muscular dystrophy – plectin mutation (premature termination codon) JAAD 41:950–956, 1999  EBS with pyloric atresia – severe blistering, often fatal; plectin mutation Int J Dermatol 50:439–442, 2011; Hum Mutat 31:308– 316, 2010; Dermatol Clin 28:43–54, 2010; mutation of integrin beta4 gene J Dermatol Sci 78:61–66, 2015  EBS superficialis – atrophic scarring, oral, conjunctival blisters AD 125:633–638, 1989  EBS, Ogna variant – autosomal dominant; plectin abnormality; seasonal blistering of the hands and feet, bruising, hemorrhagic bullae, onychogryphotic first toenails Hum Hered 23:189–196, 1973  EBS with or without neuromuscular diseases – autosomal recessive; muscular dystrophy, myasthenia gravis, spinal muscular atrophy; possible mental retardation; early death reported AD 125:931–938, 1989  EBS Mendes da Costa variant (dystrophia bullosa, typus maculatus)  EBS with superficial erosions resembling peeling skin syndrome AD 125:633–638, 1989   ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of the dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013   Junctional epidermolysis bullosa BJD 172:384–391, 2015  Junctional epidermolysis bullosa of late onset (formerly junctional epidermolysis bullosa progressiva) – loss of dermatoglyphs, waxy hyperkeratosis of the dorsal hand, atrophic skin of the lower leg, transverse ridging and enamel pits of teeth, nail atrophy, amelogenesis imperfecta, hyperhidrosis, blisters on elbows, knees, and oral cavity BJD 164:1280–1284, 2011  Kallin’s syndrome – bullae of the hands and feet, nail dystrophy, anodontia, alopecia, deafness Acta DV (Stockh) 65:526–530, 1985  Lethal autosomal recessive EBS BJD 113:135–143, 1985 Junctional EB Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 118–134   Localized forms   JEB inversa (nonlethal inverse junctional EB) – groin, perineum, axillae; heals with atrophic white streaks; late onset Proc R Soc Med 70:576–577, 1977   Nonlethal localized junctional EB – legs and feet only; hyperkeratosis with erosions of the soles J R Soc Med 78(Suppl 11); 32–33, 1985    JEB localized, other

Bullae and/or Vesicles   JEB progressiva (neurotrophic) variant – autosomal recessive Ghatan, Second Edition, 2002, p. 216   Laryngo-onycho-cutaneous syndrome – exuberant granulation tissue of the conjunctiva and larynx   Progressive junctional EB (neurotropic) – partial deafness, bullae of the hands and feet, elbows, and knees, atrophy, oral erosions JAAD 16:195–200, 1987   Cicatricial junctional EB – scarring, alopecia, syndactyly, contractures JAAD 12:836–844, 1985   Generalized forms   EB atrophicans generalisata gravis, Herlitz type – extensive blistering and erosions at birth; perioral and nasal exuberant granulation tissue; bulbous fingertips with crusting and erosions   Generalized atrophic benign EB (GABEB) (mitis) – nonlethal junctional – generalized blistering beginning in infancy; atrophic scarring; alopecia of the scalp, eyebrows, eyelashes Dermatologica 152:72–86, 1976; nevi or acquired macular pigmented lesions with irregular borders AD 122:704–710, 1986; GABEB – giant nevi at sites of blistering AD 132:145– 150, 1996    JEB cicatricial – autosomal recessive; acral muscle deformities   JEB, non-Herlitz – milder; corneal erosions, defective teeth; laminin 332 mutations    JEB, non-Herlitz – collagen 17A1 mutations   Pyloric atresia and junctional epidermolysis bullosa – large areas of denuded skin; focal segmental glomerulosclerosis; alpha6 beta4 integrins JAAD 36:304–310, 1997 Dystrophic EB Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 135–151  Localized    Inversa – waistline bullae JAAD 33:361–365, 1995   Acral   Pretibial AD 122:310–313, 1986   Centripetal   EB pruriginosa – mild acral blistering at birth or early childhood; violaceous papular and nodular lesions in linear array on shins, forearms, trunk; lichenified hypertrophic and verrucous plaques in adults BJD 130:617–625, 1994  Generalized   Dominant dystrophic – albopapuloid (Pasini) Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 152–165   Dominant dystrophic (hyperplastique) (Cockayne-Touraine variant) – nail dystrophy prominent Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 152–165   Transient bullous dermolysis of the newborn AD 121:1429– 1438, 1985    Recessive dystrophic EB, gravis (Hallopeau-Siemens variant)   Recessive dystrophic EB, mitis (mild, non-mutilating recessive dystrophic EB)   Recessive inverse dystrophic – groin, axillae, neck, lower back, nail dystrophy, oral erosions (dermolytic dystrophic), vulvar ulcers BJD 164:1104–1106, 2011; AD 124:544–547, 1988 Epidermolysis bullosa – alpha6-beta4 epidermolysis bullosa – mild blistering and crusting, severe skin fragility, patchy hyperpigmentation of the elbows; onychogryphosis; yellow-brown discoloration of teeth with enamel defects BJD 169:115–124, 2013 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive; plakophilin 1 gene mutation (PKP1) – generalized erythema and peeling at birth; widespread skin fragility and blistering, alopecia of the scalp and eyebrows, focal palmoplantar keratoderma with painful fissures, hypohidrosis; skin peeling; perioral fissuring and cheilitis; perianal erythema and erosions, follicular hyperkeratosis JAAD 58:452–457, 2008; JAAD 55:157–161, 2006; Acta DV

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85:394–399, 2005; JID 122:1321–1324, 2004; BJD 145:297–307, 1999; Nat Genet 17:240–244, 1997 Epidermolytic palmoplantar keratoderma, woolly hair, and dilated cardiomyopathy – striated palmoplantar keratoderma, follicular keratosis, clubbing, vesicles and bullae on the trunk, psoriasiform keratoses on knees, legs, and feet JAAD 39:418–421, 1998 Erythema annulare centrifugum – vesiculation, rarely Rook p. 2088, 1998, Sixth Edition Galli-Galli disease – acantholytic variation of Dowling-Degos disease; reticulated hyperpigmentation with red macules, papules, and papulovesicles JAAD 58:299–302, 2008; BJD 150:350–352, 2004; JAAD 45:760–763, 2001; Akt Dermatol 12:41–46, 1986; Hautarzt 33:378–383, 1982 Grover’s disease (transient acantholytic dermatosis) JAAD 40:471–476, 1999; JAAD 21:708–713, 1989; AD 129:1209–1210, 1993; AD 112:1440–1441, 1976 Hailey-Hailey disease – pemphigoid-like Hailey-Hailey disease – personal observation Ichthyosis bullosa of Siemens – mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray rippled hyperkeratosis of extremities, lower trunk, flexures; hypertrichosis; circumscribed patchy scaling (mauserung); palmoplantar blistering with hyperhidrosis BJD 140:689–695, 1999; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986 Junctional epidermolysis bullosa of late onset (skin fragility in childhood) – speckled hyperpigmentation of the elbows; hemorrhagic bullae, teeth and nail abnormalities, oral blisters, disappearance of dermatoglyphs, palmoplantar keratoderma, small vesicles, atrophy of skin of the hands BJD 169:714–716, 2013 Juvenile spring eruption – vesicles of helices and vermilion of the lips JAMADerm 154:1356–1357, 2018 Keratosis lichenoides chronica – vesicular and papular lesions of the palms and soles BJD 144:422–424, 2001 Lethal acantholytic epidermolysis bullosa – autosomal recessive, universal alopecia, cutaneous and mucosal shedding, skin fragility, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010; JID 130:2680–2683, 2010; BJD 162:138801394, 2010; Dermatol Clin 28:131–135, 2010; mutation in JUP gene Hum Med Genet 20:1811–1819, 2011 Lichen nitidus – vesicular linear eruption JAAD 36:630–631, 1997 Lichen planus – bullous Dermatology 190:156–159, 1995; lichen planus pemphigoides – papules and vesicles Ped Derm 31:103– 104, 2014; BJD 142:509–512, 2000; JAAD 22:626–631, 1990; ulcerative Cutis 79:37–40, 2007 Lichen planus pemphigoides – oral bullae and erosions, flat-topped papules, cutaneous bullae BJD 171:1230–1235, 2014 Lichen sclerosus et atrophicus – generalized extragenital lichen sclerosus et atrophicus – white plaques; intertriginous distribution; bullae AD 145:1303–1308, 2009; BJD 93:215–217, 1975 Necrolytic acral erythema – serpiginous, verrucous plaques of dorsal aspects of the hands, legs, initially with peripheral bullae; associated with hepatitis C infection JAAD 50:S121–124, 2004; Int J Derm 35:252–256, 1996; acral velvety hyperpigmented and hyperkeratotic plaques of distal dorsal feet; red palms with desquamation, erythroderma with flaccid bullae, edema and desquamation of the face, onychodystrophy and onychomadesis Cutis 84:301–304, 2009 Nummular dermatitis Pityriasis lichenoides et varioliformis acuta (PLEVA) Pityriasis rosea – vesicles, papulovesicles Lancet 2:493, 1971; Acta DV 42(Suppl 50):1–68, 1962

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Prurigo pigmentosa – red papules with vesiculation and crusting arranged in reticulated pattern or reticulate plaques in young women; heals with reticulated hyperpigmentation; urticarial red pruritic papules, papulovesicles, vesicles, and plaques with reticulated hyperpigmentation JAMADerm 153:353–354, 2017; JAMADerm 151:796–797, 2015; J Eur Acad Dermatol Venereol 26:1149–1153, 2012; Ped Derm 24:277–279, 2007; JAAD 55:131– 136, 2006; Am J Dermatopathol 25:117–129, 2003; Cutis 63:99– 102, 1999; JAAD 34:509–11, 1996; AD 130:507–12, 1994; BJD 120:705–708, 1989; AD 125:1551–1554, 1989; JAAD 12:165–169, 1985; Jpn J Dermatol 81:78–91, 1971 Striate palmoplantar keratoderma – autosomal dominant; hyperkeratosis of knees, intermittent blisters, and hyperhidrosis; mutation in desmoglein-1 BJD 166:36–45, 2012

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis – linear bullae due to deodorant spray Ped Derm 37:559–560, 2020; tense bulla BJD 143:229–230, 2000 JAAD 1:391–407, 1979 Salt and ice challenge – bullae of the arms; form of factitial dermatitis in teenagers Ped Derm 31:252–254, 2014

SYNDROMES Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, superficial blisters and desquamation of the hands and feet; lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears, hooked nose, sparse thin blond hair, frontal alopecia, hypohidrosis, lacrimal duct atresia, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene (encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes BJD 172:276–278, 2015; Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993 Acro-osteolysis associated with spinal dysraphism – bullae and ulcers of the foot, hyperhidrosis of the affected limb Ped Derm 18:97–101, 2001 Alagille syndrome Amniotic band syndrome Bart’s syndrome Ped Derm 17:179–182, 2000; AD 131:663–668, 1995 Behcet’s disease – vesicles JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999; JAAD 36:689–696, 1997 Bloom’s syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; blisters of the nose and cheeks; slender face, prominent nose; facial telangiectatic erythema with involvement of the eyelids, ears, hands, and forearms; bulbar conjunctival telangiectasias; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, highpitched voice, testicular atrophy; no neurologic deficits Ped Derm 22:147–150, 2005; Ped Derm 14:120–124, 1997; JAAD 17:479– 488, 1987; Am J Hum Genet 21:196–227, 1969; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954 Carvajal-like syndrome – blisters, woolly hair, palmoplantar keratoderma, cardiac abnormalities; heterozygotes of DSP (desmoplakin) BJD 166:894–896, 2012; Clin Genet 80:50–58, 2011; J Cutan Pathol 36:553–559, 2009 Congenital insensitivity to pain – bruises, burns, lacerations, and fractures mimicking child abuse Pediatr Emerg Care 12:116–121, 1996

Degos-Touraine syndrome – incontinentia pigmenti with poikiloderma in photodistribution, bullae of the face, extremities; chronic erythroderma with subsequent hyperpigmentation Soc Gr Dermatol Syph 68:6–10, 1961 Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) – Xq28 – palmar bullae with trauma Dermatol Clin 13:33–39, 1995; BJD 105:321–325, 1981 Ectodermal dysplasia/skin fragility syndrome – skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, defective sweating JAAD 58:452–457, 2008; Nat Genet 17:240–244, 1997 Familial eosinophilic cellulitis, short stature, dysmorphic habitus, and mental retardation – bullae, vesicles, and red plaques JAAD 38:919–928, 1998 Familial Mediterranean fever Cutis 37:290–292, 1986; AD 134:929– 931, 1998 Familial milia and absent dermatoglyphics – digital flexion contractures, webbed toes, palmoplantar hypohidrosis, painful fissured calluses, acral blistering, simian crease JAAD 59:1050–1063, 2008 Familial peeling skin syndrome with eosinophilia Arch Pathol Lab Med 120:662–665, 1996 Fine scaling, keratosis pilaris, periorificial crusting, palmoplantar hyperkeratosis, blistering JAAD 34:379–385, 1996 Glucagonoma syndrome JAAD 30:324–329, 1994 Goltz’s syndrome Gorham-Stout (disappearing bone) disease – lymphatic malformations (vesicle-like) with monostotic or polyostotic osteolysis JAAD 56:S21–25, 2007; J Bone Joint Surg Am 37A:985–1004, 1955; Boston Med Surg J 18:368–369, 1838 Hereditary acrokeratotic poikiloderma of Weary Ped Derm 13:427– 429, 1996; AD 103:409–422, 1971 Hypereosinophilic syndrome – vesiculobullous lesions AD 132:535– 541, 1996; Sem Derm 14:122–128, 1995; Blood 83:2759–2779, 1994 Immuno-osseous dysplasia – spondylo-epiphyseal dysplasia with short-limbed dwarfism, thrombocytopenia, subglottic stenosis, immunodeficiency, hypotonia, sparse scalp hair, bullae with decreased elastic fibers, facial dyschromatosis (mottled hyper- and hypopigmentation) Ped Derm 23:373–377, 2006 Incontinentia pigmenti, including palmar and plantar bullae in infancy Ped Derm 15:108–111, 1998; Curr Prob in Derm VII:143–198, 1995 IPEX syndrome – X-linked; immune dysregulation, polyendocrinopathy (diabetes mellitus, thyroiditis), autoimmune enteropathy; mutation of FOXP3 gene encodes DNA-binding protein that suppresses transcription of multiple genes involved in cytokine production and T-cell proliferation; atopic-like or nummular dermatitis, urticaria, scaly psoriasiform plaques of the trunk and extremities, penile rash, alopecia universalis, trachyonychia, bullae; pemphigoid nodularis (bullae and prurigo nodularis) JAAD 55:143–148, 2006; AD 140:466–472, 2004; J Pediatr 100:731–737, 1982 Job’s syndrome – neonatal vesicular rash; vesicles on the face and scalp Ped Derm 5:175–182, 1988 Kindler’s syndrome BJD 160:233–242, 2009; Ped Derm 23:586– 588, 2006; AD 140:939–944, 2004; BJD 135:503–504, 1996; Ped Derm 13:397–402, 1996; AD 132:1487–1490, 1996; JAAD 6:263–265, 1982 Lipoid proteinosis – vesicular lesions early BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002; JAAD 39: 149–171, 1998 Mendes da Costa syndrome (dystrophia bullosa, typus maculatus) – X-linked recessive; tense intraepidermal bullae, alopecia, coarse

Bullae and/or Vesicles reticulated hyperpigmentation of the face and extremities with atrophy, mental retardation Acta DV (Stockh) 18:265, 1937; intraepidermal blisters, microcephaly, mental retardation, atrichia, short conical fingers JAAD 50:S65–69, 2004 NOMID syndrome Pachyonychia congenita – palmar and plantar bullae; focal plantar keratoderma with erosions SkinMed: Dermatology for the Clinician: 233–234, July, Aug 2004; JAAD 19:705–711, 1988 Peeling skin syndrome, fissured cheilitis, blistering of the palms and soles, and desmosomal abnormalities JAAD 34:379–385, 1996

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telangiectasias and small angiomas, atrophic white macules develop; vesiculobullous lesions, superficial ulcers lead to scarring, ectropion; multiple malignancies; photophobia, conjunctivitis, ectropion, symblepharon, neurologic abnormalities Adv Genet 43:71–102, 2001; Hum Mutat 14:9–22, 1999; Mol Med Today 5:86–94, 1999; Derm Surg 23:447–455, 1997; Dermatol Clin 13:169–209, 1995; Recent Results Cancer Res 128:275–297, 1993; AD 123:241–250, 1987; Ann Int Med 80:221–248, 1974; XP variant AD 128:1233–1237, 1992

Proteus syndrome – lymphangioma circumscriptum, port-wine stains, subcutaneous hemangiomas and lymphangiomas, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation Pediatrics 76:984–989, 1985; Am J Med Genet 27:87–97, 1987; Eur J Pediatr 140:5–12, 1983

TOXINS

Reed syndrome – bullae of the fingers and soles; absence of dermatoglyphics

Mustard gas exposure AD 128:775–780, 1992; JAAD 32:765–766, 1995, JAAD 39:187–190, 1998

Relapsing polychondritis – vesicular eruption Clin Exp Rheumatol 20:89–91, 2002

Self-defense sprays (orthochlorobenzylidene malononitrile) AD 129:913, 1993

Reticulate hyperpigmentation with alopecia, nail changes, and growth retardation with or without blisters Schweiz Med Wochenschr 100:228–233, 1970; Monatsschr Kinderheilkd 78:773–781, 1939

TRAUMA

Richner-Hanhart syndrome (tyrosinemia type II) – bullae of the palms and soles; palmoplantar keratoderma Rothmund-Thomson syndrome (poikiloderma congenitale) – autosomal recessive; occasional blisters after sun exposure Am J Med Genet 22:102:11–17, 2001; Ped Derm 18:210212, 2001; Ped Derm 16:59–61, 1999; Dermatol Clin 13:143–150, 1995; JAAD 27:75–762, 1992 Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – butterfly rash, facial dermatitis, exanthema, papules, annular, atypical targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAMADerm 153:461–462, 2017; BJD 142:343–346, 2000; Clin Exp Dermatol 24:74–77, 1999; JAAD 21:374–377, 1989: AD 88:176–180, 1963

Arsenic – acute arsenic intoxication; initially morbilliform eruption with development of vesicles, pustules on red background; followed by generalized desquamation and palmoplantar lamellar desquamation BJD 141:1106–1109, 1999 Mercury poisoning – skin-colored to slightly red papules or papulovesicles of the palms or soles JAAD 49:1109–1111, 2003 Methyl bromide AD 124:917–921, 1988

Amputation stump friction blisters Burns, second degree – thermal, chemical (hydrofluoric acid) Cutis 86:249–257, 2010; Cutis 59:306–308, 1997), ultraviolet, infrared; chemical burn – bullous pemphigoid induced by chemical burn JAAD 38:337–340, 1998 Chilblains – vesicles, bullae, ischemic necrosis; calcification Child abuse – bullae from burns; stocking or glove distribution; perineal burns – annular with central sparing (doughnut lesions) around buttocks JAAD 57:371–392, 2007; JAAD 5:203–212, 1981 Coma bullae – facial bullae, linear bullae Cutis 69:265–268, 2002; Am J Dermatopathol 15:208–216, 1993; Cutis 45:423–426, 1990

SAPHO syndrome – palmoplantar pustulosis with sternoclavicular hyperostosis; non-palmoplantar pustulosis, acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis Cutis 71:63–67, 2003; Cutis 62:75–76, 1998; Rev Rheum Mol Osteoarthritic 54:187–196, 1987; Ann Rev Rheum Dis 40:547–553, 1981; with neutrophilic dermatosis (ulceronecrotic bullous Sweet’s syndrome) AD 143:275–276, 2007

Cryotherapy

Shulman’s syndrome – eosinophilic fasciitis with superficial blistering JAAD 1:221–226, 1979; Ann Rheum Dis 36:354–359, 1977

Friction blisters – pulling boat hands JAAD 12:649–655, 1985

Sweet’s syndrome – plaques with bullae BJD 178:595–602, 2018; Cutis 84:255–258, 2009; JAAD 31:535–536, 1994; BJD 76:349– 356, 1964; plaques with bullae with acute hepatitis B infection BJD 143:914–916, 2000; classical pseudovesicular border

Cupping – annulus with bullae JAMADerm 155:237, 2019 Electron beam therapy Erythema ab igne BJD 134:1151–1165, 1996 Fracture blisters – hemorrhagic and serous blisters JAMADerm 149:751–756, 2013; JAAD 30:1033–1034, 1994 Frostbite – all fingers and toes NEJM 361:2461, 2009; bullous frostbite of the neck in a snowmobiler (Polaris vulgaris) Cutis 63:21–23, 1999 Hypothermia – pink or brown discoloration with blisters over joints JAAD 64:811–824, 2011

Wells’ syndrome (eosinophilic cellulitis) – bullous, papulovesicular lesions, vesiculobullous plaques JAMADerm 155:617–618, 2019; Ped Derm 29:762–764, 2012; AD 143:791–796, 2007; AD 142:1157–1161, 2006; AD 139:933–938, 2003; BJD 143:425–427, 2000; BJD 140:127–130, 1999; AD 133:1579–1584, 1997; JAAD 33:857–64, 1995; JAAD 18:105–114, 1988; Trans S. Johns Hosp Dermatol Soc 51:46–56, 1971; insect bite-like Wells’ syndrome in association with lymphoma – recurrent papulovesicles, vesicles, and bullae of the face, trunk, and extremities BJD 155:614–616, 2006

Immersion foot due to ice, cold water, and fans – acral cyanosis, mottled coloration, marked edema of the feet, maceration, bullae, erosions, painful ulcers, pain JAAD 69:169–171, 2013; acral bullae Derm Clinics 17:1–17, 1999

Xeroderma pigmentosum – acute sunburn, persistent erythema, freckling – initially discrete, then fuse to irregular patches of hyperpigmentation, dryness on sun-exposed areas; with time

Nerve injury, traumatic – surgical injury to lateral femoral cutaneous nerve with bulla and subsequent ulceration of the lateral lower leg Dermatol Wochenschri 136:971–973, 1957

Inhalant abuse – frostbite; orofacial bullae, finger bullae Intravenous infiltration – personal observation Neonatal sucking blister – fingers, lips, forearms Pediatrics 32:1099–2001, 1963

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Pressure bullae – personal observation Pressure urticaria – bullous delayed pressure urticaria BJD 153:435–439, 2005 Radiation dermatitis, acute JAAD 54:28–46, 2006; Acta DV 49:64–71, 1969; lymphangiomatous papules following radiation therapy Histopathology 35:319–327, 1999; bullae of the breast – lymphangiectasias (benign lymphangiomatous papules) at the site of radiation therapy AMA Arch Derm 74:466–468, 1956; bulla of the legs with pruritic eruption with eosinophilia AD 137:821–822, 2001; eosinophilic polymorphic and pruritic eruption associated with radiotherapy (EPPER) – bullae, red papules, pruritic AD 137:821–822, 2001 Radiation recall – erythema, vesiculation, erosions, hyperpigmentation; dactinomycin and doxorubicin, taxanes, gemcitabine, capecitabine The Oncologist 15:1227–1237, 2010; Mayo Clin Proc 55:711–715, 1980; edatrexate, melphalan, etoposide, vinblastine, bleomycin, fluorouracil, hydroxyurea, methotrexate Subcutaneous emphysema of the eyelids – bullae over medial canthi Superficial mucocele – oral bulla Tape stripping bullae

VASCULAR Chylous reflux BJD 120:695–700, 1989 Churg-Strauss disease – vesicles and bullae JAAD 47:209–216, 2002; Medicine 78:26–37, 1999 Edema – acute edema bullae of the legs BJD 144:580–582, 2001 Erythema elevatum diutinum – PCT-like bullae BJD 124:89–91, 1991; perilesional vesicles and bullae Ann DV 104:75–76, 1977; BJD 80:178–183, 1968 Erythromelalgia – edema and bullae of the legs BJD 151:708–710, 2004 Granulomatosis with polyangiitis JAAD 31:605–612, 1994 Henoch-Schonlein purpura Ped Derm 15:357–359, 1998; Ped Derm 12:314–317, 1995 Lymphangiectasia, acquired – hypertrophic vesicular lesions of the vulva; due to scarring processes such as hysterectomy and radiation; recurrent infections, radiotherapy, scrofuloderma (tuberculous adenitis), tumors, genital Crohn’s disease Cutis 90:291–292, 2012; AD 148:755–760, 2012 Lymphangioma circumscriptum (benign lymphangiectasia) (microcystic lymphatic malformation) JAMA 321:1213–1214, 2019; Cutis 76:310–311, 2005; BJD 83:519–527, 1970 Lymphangioma, diffuse – may or may not have widely distributed vesicles BJD 134:1135–1137, 1996; AD 129:194–197, 1993 Lymphangiosarcoma (Stewart-Treves tumor) – bullae and nodules in lymphedematous extremity Arch Surg 94:223–230, 1967; Cancer 1:64–81, 1948 Lymphatic malformations JAAD 56:S21–25, 2007 Lymphedema, including congenital lymphedema (Milroy’s disease); engorged dermal lymphatics mimicking appearance of vesicles; lymphangiectasias – personal observation Polyarteritis nodosa – in children; fever, peripheral gangrene, black necrosis, livedo reticularis, ulcers, nodules, vesiculobullous lesions, arthralgia, nodules of the face and extremities, conjunctivitis JAAD 53:724–728, 2005; Ann Rheum Dis 54:134–136, 1995 Reactive angioendotheliomatosis – red-purple purpuric patches and plaques; includes acroangiomatosis, diffuse dermal angiomatosis, intravascular histiocytosis, glomeruloid angioendotheliomatosis, angiopericytomatosis: (angiomatosis with cryoproteins); associated with subacute bacterial endocarditis, hepatitis, cholesterol emboli, arteriovenous shunt, antiphospholipid antibody syndrome, chronic

lymphocytic leukemia, monoclonal gammopathy, chronic renal failure, rheumatoid arthritis JAAD 49:887–896, 2003 Reperfusion bulla with limb ischemia – personal observation Sickle cell vaso-occlusion BJD 178:305–306, 2018 Stasis bullae Symmetric peripheral gangrene – personal observation Temporal arteritis – bullae of the scalp BJD 76:299–308, 1964 Urticarial vasculitis, including urticarial vasculitis associated with mixed cryoglobulins, hepatitis B or C infection, IgA multiple myeloma, infectious mononucleosis, monoclonal IgM gammopathy (Schnitzler’s syndrome), fluoxetine ingestion, metastatic testicular teratoma, serum sickness, Sjögren’s syndrome, systemic lupus erythematous JAAD 38:899–905, 1998; Medicine 74:24–41, 1995; JAAD 26:441–448, 1992 Vasculitis – idiopathic, drug-induced Cutis 67:303–307, 2001; acantholytic vesicular dermatitis with leukocytoclastic vasculitis JAAD 15:1083–1089, 1986 Congenital Volkmann ischemic contracture (neonatal compartment syndrome) – upper extremity circumferential contracture from wrist to elbow; necrosis, cyanosis, edema, eschar, bullae, purpura; irregular border with central white ischemic tissue with formation of bullae, edema, or spotted bluish color with necrosis, a reticulated eschar or whorled pattern with contracture of the arm; differentiate from necrotizing fasciitis, congenital varicella, neonatal gangrene, aplasia cutis congenital, amniotic band syndrome, subcutaneous fat necrosis, epidermolysis bullosa BJD 150:357–363, 2004 Venous gangrene – personal observation

BULLAE, HEMORRHAGIC  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis to poison ivy Bullous pemphigoid Clin Exp Dermatol 13:242–243, 1988; hemorrhagic bullae of the hands BJD 168:1357–1360, 2013 Cicatricial pemphigoid – including hemorrhagic bullae of the buccal mucosae; adult or childhood form of cicatricial pemphigoid Dermatitis herpetiformis JAAD 16:1274–1276, 1987; hemorrhagic bullae of the palms and soles Ped Derm 11:319–322, 1994 Epidermolysis bullosa acquisita, including buccal mucosa JAAD 11:820–832, 1984; hemorrhagic bullae of the palms JAAD 54:888– 891, 2006 Graft vs. host disease Linear IgA disease (chronic bullous disease of childhood) – perioral, eyelids, ears, scalp, perineum, vulva; annular polycyclic bullae; hemorrhagic bullae Ped Derm 15:108–111, 1998; neonatal linear IgA disease Ped Derm 10:171–176, 1993 Lupus erythematosus – systemic lupus – bullous sunburn reaction BJD 82:125–128, 1970; AD 83:910–914, 1961 Mixed connective tissue disease – with vasculitis Morphea Cutis 44:118–119, 1989 Pemphigus vulgaris – personal observation Rheumatoid vasculitis JAAD 53:191–209, 2005; BJD 147:905–913, 2002; AD 125:1101–1104, 1989

CONGENITAL LESIONS Aplasia cutis congenita Ped Derm 21:150–153, 2004

Bullae, Hemorrhagic

DRUG-INDUCED

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Anti-PD-1 therapy (atezolizumab, nivolumab, pembrolizumab, durvalumab) – bullous dermatoses (bullous pemphigoid, IgA dermatosis) – hemorrhagic bullae, urticarial plaques, oral ulcers JAAD 79:1081–1088, 2018

Anthrax – Bacillus anthracis; malignant pustule; face, neck, hands, arms; starts as papule, then evolves into bulla on red base; then hemorrhagic and necrotic crust with edema and erythema with small satellite vesicles; edema of surrounding skin; black eschar, then painless ulcer JAAD 65:1213–1218, 2011; Am J Dermatopathol 19:79–82, 1997; J Clin Inf Dis 19:1009–1014, 1994; Br J Ophthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981

Bullous pemphigoid – penicillin, sulfasalazine, topical 5-fluorouracil, PUVA, electron beam radiotherapy Clinics in Derm 11:515–520, 1993; vildagliptin (dipeptidyl peptidase-4 inhibitor)-induced bullous pemphigoid JAMADerm 149:243–245, 2013

Aspergillosis – primary cutaneous JAAD 38:797–798, 1998; primary cutaneous aspergillosis in premature infants Ped Derm 19:439–444, 2002; AD 136:1165–1170, 2000; JAAD 12:313–318, 1985; sepsis in leukemic patients AD 141:633–638, 2005

Chemotherapy extravasation

Brown recluse spider bite – cyanotic pale hemorrhagic bulla progresses to eschar; sunken bluish patch JAAD 67:347–354, 2012

Acute generalized exanthematous pustulosis – pustules and hemorrhagic bullae AD 147:697–670, 2011

Coumarin (warfarin) necrosis – begins as paresthesia, then progresses to edema, petechiae, ecchymosis, hemorrhagic bulla, and necrosis; preferential sites are abdomen, buttocks, thighs, legs, breasts; may occur acrally; associated with protein C deficiency (autosomal dominant); begins 3–5 days after commencing coumarin therapy JAAD 61:325–332, 2009; JAAD 60:1–20, 2009; Acta Med Scand 148:453–462, 1954; NYS J Med 43:1121, 1943; Am J Physiol 41:250–257, 1916 Enoxaparin – bullous hemorrhagic dermatosis JAMADerm 149:871–872, 2013 Fixed drug reaction Gemcitabine extravasation Heparin-induced thrombocytopenia – personal observation Heparin necrosis – at a distant site from subcutaneous heparin injection JAAD 54:55–57, 2006 Imatinib mesylate – pseudo-PCT; hemorrhagic bullae of side of the hand; crusts and erythema of the dorsal hands Ped Derm 31:603– 607, 2014 Iododerma Australas J Dermatol 28:119–122, 1987; intravenous radiocontrast material Clin Exp Dermatol 44:844–860, 2019 Linear IgA disease – somatostatin, vancomycin, captopril, phenytoin, lithium, diclofenac, cefamandole, amiodarone, furosemide JAAD 41:103–105, 1999; Clinics in Derm 11:529–533, 1993 Nilotinib – bullous Sweet’s syndrome in chronic myelogenous leukemia treated with tyrosine kinase inhibitor nilotinib AD 144:361– 364, 2008 Penicillamine – hemorrhagic bullae of the dorsum of the feet AD 95:196–198, 1967 Phenylephrine-induced microvascular occlusion syndrome – livedo racemosa, acral cyanosis and necrosis with hemorrhagic bullae AD 143:1314–1317, 2007 PPD reaction – bullous Rituximab vasculitis AD 142:2446–247, 2006 Ustekinumab – leukocytoclastic vasculitis – purpuric necrotic targetoid bullae J Drugs Dermatol 15:358–361, 2016 Vasculitis, leukocytoclastic – drug-induced

EXOGENOUS AGENTS Levamisole-contaminated cocaine – snorting, injection, smoking; ecchymoses, bullae, stellate lesions with red borders and necrotic center; especially on ears and cheeks Clin Inf Dis 61:1840–1849, 2015

Brucellosis Caterpillar dermatitis – puss caterpillar (larval stage of flannel moth, Megalopyge opercularis) – hemorrhagic papulovesicles or bullae Cutis 71:445–448, 2003 Chromobacterium violaceum – ecthyma gangrenosum JAAD 54:S224–228, 2006 Clostridium perfringens/septicum Ann Emerg Med 10:312–314, 1981 Coxsackie-associated leukocytoclastic vasculitis – personal observation Cowpox – papule progresses to vesicle to hemorrhagic vesicle to umbilicated pustule, then eschar with ulcer JAAD 44:1–14, 2001; BJD 1331:598–607, 1994 Ecthyma gangrenosum   Pseudomonas   Aeromonas hydrophila   Xanthomonas maltophilia   Aspergillus species   Candida albicans   Capnocytophaga canimorsus   Chromobacterium violaceum JAAD 54:S224–228, 2006   Gram-negative rods Endocarditis – subacute bacterial endocarditis; Osler’s nodes (painful hemorrhagic bulla of the thumb tip); extensive distal purpura with necrosis of the legs; Janeway lesion – purpuric macule of the sole; conjunctival hemorrhage JAMADerm 150:494–500, 2014 Enterobacter cloacae JAAD 27:637–638, 1992; Rev Infect Dis 44:13–28, 1982 Erysipelas, bullous – personal observation Fire coral (Millepora spp.) – scuba divers; dermatitis, bullae, hemorrhagic bullae, necrosis, ulceration, urticaria; late lichenoid and granulomatous reactions JAAD 61:733–750, 2009 Flavobacterium odoratum – necrotizing fasciitis J Clin Inf Dis 21:1337–1338, 1995 Gonococcemia – periarticular lesions appear in crops with red macules, papules, vesicles with red halo, pustules, bullae becoming hemorrhagic and necrotic; suppurative arthritis and tenosynovitis Ann Int Med 102:229–243, 1985; NEJM 282:793– 794, 1970 Atypical hand, foot, and mouth disease – Coxsackie A6; hemorrhagic bullae of the palms, dorsal hands, and fingers; perioral papulovesicles JAAD 76:722–729, 2017 Herpes simplex Herpes zoster

INFECTIONS AND/OR INFESTATIONS Aeromonas sobria Pathol Int 49:541–546, 1999

Impetigo Insect bite reaction Klebsiella sepsis

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Leprosy – erythema nodosum leprosum AD 132:1432–1434, 1996; nerve involvement – plantar hemorrhagic bulla

Langerhans cell histiocytosis – purpuric vesicles JAAD 37:314–317, 1997; JAAD 13:481–496, 1985

Lyme disease NEJM 321:586–596, 1989; AD 120:1017–1021, 1984; Science 216:1317–1319, 1982

Mastocytosis – bullous mastocytosis presents before the age of 9 months; occurs in the absence of pigmentary changes and without lesions of urticaria pigmentosa; if present in infancy, extracutaneous involvement is common Ped Derm 19:375–381, 2002; AD 127:1049–1054, 1991; AD 101:547–562, 1970

Meningococcemia – acute or chronic (petechial); acute; initially ecchymoses, purpuric papules and plaques with surrounding erythema, vesicles, bullae, hemorrhagic necrosis, purpura fulminans Morganella morganii JAAD 12:575–576, 1985 Necrotizing fasciitis AD 138:893–898, 2002 Nocardia asteroides AD 121;898, 1985 Orf AD 126:356–358, 1990; Isr J Med Sci 24:54–56, 1988 Papular-purpuric gloves and socks syndrome J Dermatol 29:371– 375, 2002 Pneumococcal cellulitis AD 132:81–86, 1996 Portuguese man-of-war Proteus mirabilis Pseudomonas sepsis Purpura fulminans (disseminated intravascular coagulation) – variety of bacterial, fungal, and viral organisms Salmonella NY State J Med 81:1639–1641, 1981 Scorpion sting – pain, necrosis, hemorrhagic bullae; pulmonary edema, shock, death JAAD 67:347–354, 2012 Sea anemone sting Smallpox Snake bite Spider bites – brown recluse spider bite Clin Inf Dis 32:595,636– 637, 2001 Staphylococcal sepsis Subacute bacterial endocarditis Tropical ulcer (phagedenic ulcer) – mixed infection with Fusobacterium ulcerans and other organisms; papule or bulla (hemorrhagic) which breaks down to form ulcer with undermined border Int J Dermatol 27:49–53, 1988 Typhoid fever Varicella Vibrio cholera non-O1 Clin Inf Dis 21:1330–1333, 1995 Vibrio vulnificus Clin Inf Dis 40:718,754–755, 2005; AD 122:818– 820, 1986

INFILTRATIVE DISORDERS Amyloidosis, bullous – the separation of epidermis and dermis occurs within the dermal deposits of amyloid; protein AL consists of a polypeptide of light chain immunoglobulin composed of fragments of the variable (amino-terminal) region; clinical lesions include petechiae, purpura, ecchymoses, plaques, tumefactive lesions, pigmentary changes, scleroderma-like infiltration, bullae, alopecia, cord-like blood vessel thickening, nail dystrophy, and cutis laxa Eur J Dermatol 10:139–142, 2000; Medicine 24:124–128, 1994; Cutis 43:346–352, 1989; AD 124:1683–1686, 1988; BJD 113:85–95, 1985; AD 117:782–784, 1981; oral hemorrhagic bullae in primary systemic amyloidosis Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:734–740, 2006; blistering purpuric perianal eruption JAMADerm 151:1367–1368, 2015 Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease) Ped Derm 23:273–275, 2006; JAAD 48:S75–77, 2003

INFLAMMATORY DISORDERS Erythema multiforme with epidermal necrosis Neutrophilic dermatosis of the dorsal hand (pustular vasculitis of the hands) AD 144:255–260, 2008; JAAD 43:870–874, 2000; JAAD 32:192–198, 1995 Pyoderma gangrenosum, bullous BJD 102:235–237, 1980; Trans St John’s Hosp Dermatol Soc 60:142–151, 1974; association with polycythemia vera Clin Exp Dermatol 12:375–377, 1987; leukemia JAAD 9:751–758, 1983; CML Proc R Soc Med 67:1239–1240, 1974; hairy cell leukemia JAAD 11:300–302, 1985 Stevens-Johnson syndrome – personal observation Sweet’s syndrome – edematous red nodules, hemorrhagic bullae, subcutaneous red nodule JAAD 79:987–1006, 2018

METABOLIC Acrodermatitis enteropathica Calciphylaxis (vascular calcification cutaneous necrosis syndrome) (cutaneous calcinosis in end-stage renal disease) – necrotic cutaneous ulcers, livedo racemosa, hemorrhagic patches, indurated plaques, hemorrhagic bullae JAAD 56:569–579, 2007; Ped Derm 23:266–272, 2006 Catastrophic antiphospholipid antibody syndrome – personal observation Cryofibrinogenemia AD 144:405–410, 2008 Cryoglobulinemia – mixed cryoglobulinemia secondary to hepatitis C infection Cutis 72:290,295, 2003 Interstitial cryoglobulinosis – non-palpable petechial purpura, necrotic ulcers, hemorrhagic bullae; renal failure JAAD 77:1145– 1158, 2017 Diabetic bulla – intraepidermal or subepidermal separation without acantholysis JAAD 7:427–455, 1982 Disseminated intravascular coagulation – purpura fulminans, symmetric peripheral gangrene; obstetric complications, extensive tissue damage, gram-negative septicemias, immune reactions, malignancy, snake bites, angiomas, protein S or protein C deficiency JAAD 60:1–20, 2009; Br Med J 312:683–687, 1996; BJD 88:221–229, 1973 Hyperhomocysteinemia and antiphospholipid antibodies JAAD 49:S161–163, 2003 Neonatal purpura fulminans – ecchymoses of the limbs at sites of pressure in the first day of life; enlarge rapidly, hemorrhagic bullae with central necrosis; homozygous protein C or protein S deficiency Semin Thromb Hemost 16:299–309, 1990 Paroxysmal nocturnal hemoglobinuria – petechiae, ecchymoses, red plaques which become hemorrhagic bullae with necrosis; lesions occur on the legs, abdomen, chest, nose, and ears; deficiency of enzymes – decay-accelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL); acquired intravascular hemolytic anemia; due to a drop in pH of serum during sleep; Ham test (acid hemolysis); sucrose lysis test, low leukocyte alkaline

Bullae, Hemorrhagic phosphatase; anemia, hemoglobinuria (dark urine), increased serum hemoglobin, hemosiderinuria; abdominal pain, recurrent infections, headache, venous thrombosis, progressive bone marrow failure, and ultimately lymphoreticular malignancy (especially leukemia) AD 148:660–662, 2012; AD 138:831–836, 2002; AD 122:1325–1330, 1986; AD 114:560–563, 1978; livedo racemosa, painful ecchymoses, purpura, hemorrhagic bullae, ulcers; mutation PIGA gene which encodes glycosylphosphatidylinositol-anchored proteins (decrease in GPI proteins in cell membranes); complement-induced intravascular hemolysis; increased thrombosis BJD 171:908–910, 2014 Pellagra Cutis 69:96–98, 2002; Semin Dermatol 10:282,1991 Porphyria cutanea tarda Am J Med 67:277–286, 1979; Med Clin NA 64:807–827, 1980 Pseudo-PCT – hemorrhagic bullae of the dorsal hands JAAD 66:865–866, 2012 Renal failure with or without furosemide Scurvy JAAD 41:895–906, 1999

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Epidermolysis bullosa, many types; EBS herpetiformis – DowlingMeara – begins in infancy with hemorrhagic blisters of the fingers and toes JAAD 28:859–861, 1993; EBS, Ogna variant – autosomal dominant; plectin abnormality; seasonal blistering of the hands and feet, bruising, hemorrhagic bullae, onychogryphotic first toenails Hum Hered 23:189–196, 1973; epidermolysis simplex with mottled pigmentation – acral blistering, hemorrhagic bullae, focal punctate keratoderma, dystrophic thick nails BJD 144:40–45, 2001 Epidermolysis bullosa atrophicans generalisata mitis JAAD 12:836–844, 1985 Erythema elevatum diutinum AD 132:1360–1364, 1996 Febrile ulceronecrotic Mucha-Habermann disease (acute parapsoriasis) JAAD 55:557–572, 2006; NJAAD 54:1113–1114, 2006; Ped Derm 22:360–365, 2005; BJD 152:794–799, 2005; JAAD 49:1142– 1148, 2003; BJD 147:1249–1253, 2002; Ped Derm 8:51–57, 1991; AD 100:200–206, 1969; Ann DV 93:481-496, 1966 Junctional epidermolysis bullosa of late onset (skin fragility in childhood) BJD 169:714–716, 2013

Symmetric peripheral gangrene – pneumococcal sepsis – personal observation

Lichen nitidus AD 105:430–431, 1972

Wilson’s disease JAAD 21:1030, 1989

Lichen sclerosus et atrophicus, bullous JAAD 39:500–501, 1998; JAAD 10:346–350, 1984

NEOPLASTIC DISEASES

Lichen planus, bullous, erosive – personal observation

Toxic erythema of the newborn Transient acantholytic dermatosis (Grover’s disease)

Congenital self-healing reticulohistiocytosis JAAD 48:S75–77, 2003 Lymphoma – cutaneous T-cell lymphoma Bull Soc Fr Derm Syph 73:373–376, 1966; HTLV-1 lymphoma JAAD 46:S137–141, 2002

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis

PARANEOPLASTIC DISEASES Henoch-Schonlein purpura – associated with metastatic prostate cancer JAAD 55:565–570, 2006 Eosinophilic dermatitis of hematologic malignancy (mosquito bite hypersensitivity syndrome in EBV-associated natural killer cell leukemia/lymphoma) – clear or hemorrhagic bullae with necrosis, ulceration, and scar formation JAAD 45:569–578, 2001 Paraneoplastic pemphigus BJD 144:1255–1261, 2001; hemorrhagic bullae of the palms BJD 169:469–472, 2013

PHOTOSENSITIVITY DISORDERS Hydroa vacciniforme – red macules progress to tender papules, hemorrhagic vesicles or bullae of the face and hands, umbilication and crusting; varioliform (pock-like) scars; keratoconjunctivitis and uveitis, blistering of the lips JAAD 67:1093, 1110, 2012; Ped Derm 18:71–73, 2001; JAAD 42:208–213, 2000; Dermatology 189:428– 429, 1994; JAAD 25:892–895, 1991; JAAD 25:401–403, 1991; BJD 118:101–108, 1988; AD 118:588–591, 1982; familial BJD 140:124– 126, 1999; AD 114:1193–1196, 1978; AD 103:223–224, 1971; late onset BJD 144:874–877, 2001 Polymorphous light eruption Sunbed use BMJ 296:1708, 1988

PRIMARY CUTANEOUS DISEASE Angina bullosa hemorrhagica JAAD Case Rep 2:433–435, 2016; AD 135:593–598, 1999 Balanitis xerotica obliterans JAAD 37:1–24, 1997 Benign hemorrhagic bullous stomatitis Ann DV 126:525–526, 1999 Darier’s disease of the hands and feet AD 89:523–527, 1964

SYNDROMES Antiphospholipid antibody syndrome Behcet’s disease JAAD 36:689–696, 1997 Eosinophilic dermatitis of hematologic malignancy (formerly exaggerated insect bite-like reaction associated with hematologic malignancy) (mosquito bite hypersensitivity syndrome in EBVassociated natural killer cell leukemia/lymphoma) – clear or hemorrhagic bullae with necrosis, ulceration, and scar formation JAAD 81:74–75, 2019; JAAD 45:569–578, 2001 Ichthyosiform dermatosis with superficial blister formation and peeling JAAD 34:379–385, 1996 Lipoid proteinosis Ped Derm 23:1–6, 2006 Kindler’s syndrome Reflex sympathetic dystrophy (bullae on the dorsal foot) JAAD 28:29–32,1993 Sweet’s syndrome – predominance of women; upper extremities, neck and upper trunk; arthralgias, conjunctivitis, episcleritis, aphthosis, proteinuria, and high ESR; 10–15% associated with malignancy, most commonly acute myelogenous leukemia, giant cellulitis-like; bullae and purpura JAMADerm 149:79–83, 2013; in malignancy-associated Sweet’s syndrome, male-to-female ratio is 1:1 and patients more likely to have bullous or ulcerative lesions AD 145:344–346, 2009; JAAD 54:745–762, 2006; AD 126:527–532, 1990 Wells’ syndrome AD 143:791–796, 2007

TRAUMATIC Altitude injury – petechiae and hemorrhagic bullae of external auditory canal in pilots descending from high altitudes Laryngoscope 56:225–236, 1946

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Burns, electrical, thermal, ultraviolet Coma bullae – sweat gland necrosis Cutis 45:423, 1990 Cryotherapy Erythema ab igne Fracture bullae (blisters) – hemorrhagic and serous blisters JAMADerm 149:751–756, 2013 Frostbite Intramuscular hematoma – personal observation Pressure bullae, pressure necrosis – personal observation Physical trauma – personal observation Sunburn

Anthrax – Bacillus anthracis; malignant pustule; face, neck, hands, arms; starts as papule, then evolves into bulla on red base; then hemorrhagic crust with edema and erythema with small vesicles; edema of surrounding skin Am J Dermatopathol 19:79–82, 1997; J Clin Inf Dis 19:1009-1014, 1994; Br J Ophthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981 Aspergillosis JAAD 80:869–880, 2019; AD 141:633–638, 2005; AD 136:1165–1170, 2000; JAAD 12:313–318, 1985; Aspergillus fumigatus – ecthyma gangrenosum Clin Microbiol 36:3115–3121, 1998; Rev Infect Dis 2:854–866, 1980; primary cutaneous aspergillosis in premature infants Ped Derm 19:439–444, 2002; primary cutaneous JAAD 38:797–798, 1998 Bacillus cereus AD 127:543, 1991

VASCULAR

Candida albicans – ecthyma gangrenosum JAAD 80:869–880, 2019; Am J Med 70:1133–1135, 1981; AD 115:214–215, 1979

Acquired digital arteriovenous malformation BJD 142:362–365, 2000

Capnocytophaga canimorsus

Eosinophilic granulomatosis with polyangiitis Case Rep Dermatol 11:28–35, 2019; BJD 150:598–600, 2004; JAAD 47:209–216, 2002; J Dermatol 22:46–51, 1995

Cellulitis of the extensor compartment

Granulomatosis with polyangiitis Adv Exp Med Biol 755:307–310, 2013; BJD 143:207–209, 2000; AD 113:175–182, 1977 Henoch-Schonlein purpura BMC Ped 18:157, 2018; Rheumatol Int 30:1355–1359, 2010; Ped Derm 23:139–141, 2006; AD 139:215– 220, 2003; Ped Derm 15:357–359, 1998; Ped Derm 12:314–317, 1995; Wis Med J 84:21–23, 1985; in children Cutis 96:248–25, 2015; Ped Derm 23:139–141, 2006; Ped Int 47:694–697, 2005; J Microbiol Immunol Infect 37:375–378, 2004; Dermatology 197:62– 64, 1998; AD 126:1497–1498, 1990

Cellulitis JAAD 67:163–174, 2012 Chromobacterium violaceum – ecthyma gangrenosum JAAD 54:S224–228, 2006 Citrobacter freundii – ecthyma gangrenosum JAAD 50:s114–117, 2004; JAAD 5:613, 1981 Clostridium perfringens/septicum NEJM 323:1406, 1990; Ann Emerg Med 10:312–314, 1981 Corynebacterium diphtheriae – ecthyma gangrenosum Int J Derm 30:845–847, 1991

Ischemic gangrene; ischemic bullae – personal observation

Cowpox – papule progresses to vesicle to hemorrhagic vesicle to umbilicated pustule, then eschar with ulcer JAAD 44:1–14, 2001; BJD 1331:598–607, 1994

Livedo racemosa – emboli following catheterization; personal observation

Curvularia spp. – ecthyma gangrenosum Bone Marrow Transplant 27:1311–1313, 2001

Polyarteritis nodosa, systemic – cutaneous infarcts presenting as purpuric plaques

Cytomegalovirus JAAD 11:743–747, 1984

Purpura fulminans – symmetric peripheral gangrene; meningococcemia, staphylococcal sepsis, Capnocytophaga canimorsus JAAD 57:944, 956, 2007; Br Med J 2:8–9, 1891

Disseminated intravascular coagulation (DIC) – gram-negative septicemias Br Med J 312:683–687, 1996; BJD 88:221–229, 1973; variety of infections

Pustular vasculitis of the hands JAAD 32:192–198, 1995

Ecthyma gangrenosum   Aeromonas hydrophila NY State J Med 82:1461–1464, 1982   Pseudomonas aeruginosa   Enteric rods   Aeromonas hydrophila   Xanthomonas maltophilia   Aspergillus species   Candida albicans   Capnocytophaga canimorsus  Methicillin-resistant Staphylococcus aureus Cutis 90:67–69, 2012

Reperfusion bulla with vasospasm – personal observation Vasculitis – large and/or small vessel – leukocytoclastic vasculitis; urticarial vasculitis AD 134:231–236, 1998 Venous gangrene (acral) (phlegmasia cerulea dolens) – massive proximal venous thrombosis resulting in arterial insufficiency; triad of asymmetric leg edema, hemorrhagic bullae, cyanosis, acral necrosis, pain; combination of severe pain, extensive edema, and cyanosis of the limb; in arterial gangrene edema is absent or minimal, cutaneous hemorrhage does not occur, skin is pale, subcutaneous veins are poorly filled and empty with leg elevation NEJM 370:1742–1748, 2014; JAAD 60:1–20, 2009; AD 123:933– 936, 1987

BULLAE, HEMORRHAGIC, SEPTIC Acinetobacter baumannii – edematous cellulitis with small vesicles and hemorrhagic bullae after war trauma JAAD 75:1–16, 2016; Clin Infect Dis 47:444–449, 2008 Aeromonas hydrophila – ecthyma gangrenosum NY State J Med 82:1461–1464, 1982 Aeromonas sobria Pathol Int 49:541–546, 1999

Dermatophyte infection

Enterobacter cloacae JAAD 27:637–638, 1992; Rev Infect Dis 44:13–28, 1982 Erysipelas Singapore Med J 49:809–813, 2008 Escherichia coli J Clin Gastroenterol 4:145–148, 1982; AD 110:105– 106, 1974; ecthyma gangrenosum Cutis 84:261–267, 2009; Infect Med 15:798–801, 1998; Postgrad Med 79:44–45, 1986; J Clin Gastroenterol 4:145–148, 1982; S Afr Med J 55:504–508, 1979 Exserohilum spp. – ecthyma gangrenosum Ped Derm 20:495–497, 2003 Flavobacterium odoratum – necrotizing fasciitis J Clin Inf Dis 21:1337–1338, 1995 Fusarium, localized – plantar hemorrhagic bulla JAAD 47:659–666, 2002; Fusarium solani – ecthyma gangrenosum JAAD 80:869–880,

Bullae in Newborn 2019; Clin Microbiol Rev 20:695–704, 2007; Curr Opin Infect Dis 13:121–128, 2000; Clin Exp Dermatol 20:428–430, 1995; AD 123:167–168, 1987; F. falciforme – red plaques, vesicles, pustules, necrosis BJD 157:407–409, 2007 Gonococcemia – periarticular lesions appear in crops with red macules, papules, vesicles with red halo, pustules, bullae becoming hemorrhagic and necrotic; suppurative arthritis and tenosynovitis Ann Int Med 102:229–243, 1985; NEJM 282:793– 794, 1976; AD 96:74–76, 1967; ecthyma gangrenosum AD 96:74–76, 1967 Atypical hand, foot, and mouth disease – Coxsackie A6; hemorrhagic bullae of the palms, dorsal hands, and fingers; perioral papulovesicles JAAD 76:722–729, 2017 Herpes simplex infection – ecthyma gangrenosum Clin Inf Dis 29:454–455, 1999 Herpes zoster Klebsiella pneumoniae – ecthyma gangrenosum Int J Derm 34:216–217, 1995 Lyme disease – personal observation Meningococcemia JAMA 134:513–518, 1947 Metarhizium anisopliae – ecthyma gangrenosum J Clin Microbiol 36:1146–1150, 1998 Morganella morganii – ecthyma gangrenosum BJD 139:520–521, 1998; JAAD 12:575–576, 1985 Mucor pusillus – ecthyma gangrenosum AD 113:1075–1076, 1977 Mucormycosis – Mucor, Rhizopus oryzae, Rhizomucor, Lichtheimia, Saksenaea, Cunninghamella, Apophysomyces JAAD 80:869–880, 2019; AD 113:1075–1076, 1977

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Serratia marcescens – ecthyma gangrenosum Rev Infect Dis 2:854–866, 1980 Smallpox – macular and papular exanthems of the face and extremities develop vesicles, pustules, and umbilicated crusts; hemorrhagic smallpox more severe JAAD 65:1213–1218, 2011 Staphylococcus aureus sepsis – ecthyma gangrenosum Ped Derm 29:320–323, 2012; Arch Int Med 147:1513, 1987; methicillin-resistant Staphylococcus aureus – ecthyma gangrenosum (hemorrhagic necrotic bulla) Cutis 90:67–69, 2012 Streptococcus pneumoniae sepsis AD 132:81–86, 1996 Streptococcus pyogenes, group A – ecthyma gangrenosum Arch Int Med 147:1513, 1987 Subacute bacterial endocarditis – Streptococcus viridans – personal observation Toxic shock syndrome JAAD 10:267–272, 1984 Trichosporon beigelii Mayo Clin Prog 58:684, 1983 Tropical ulcer (phagedenic ulcer) – mixed infection with Fusobacterium ulcerans and other organisms; papule or bulla (hemorrhagic) which breaks down to form ulcer with undermined border Int J Dermatol 27:49–53, 1988 Typhoid fever Non-O1 Vibrio cholerae JAAD 29:909–912, 1993 Vibrio vulnificus – primary or septicemic NEJM 379:375, 2018; JAAD 61:733–750, 2009; Clin Inf Dis 40:718,754–755, 2005; BJD 142:386–387, 2000; Int J Dermatol 28:313–316, 1989; AD 122:818– 820, 1986; JAAD 12:575–576, 1983

Necrotizing fasciitis AD 138:893–898, 2002

Xanthomonas maltophilia – ecthyma gangrenosum Arch Int Med 147:1672–1674, 1987; J Clin Microbiol 24:995–997, 1986; Postgrad Med 79:44–45, 1986

Nocardia asteroides AD 121;898, 1985

Yersinia enterocolitica Am J Med Sci 287:38, 1984

Orf – reactive erythema multiforme Clin Inf Dis 56:1613, 1675– 1676, 2013; AD 126:356, 1990

Yersinia pestis – ecthyma gangrenosum West J Med 142:641–646, 1985

Paronychial bullae – bacterial sepsis Dermatol Clin 33:207–241, 2015 Phaeohyphomycosis – Alternaria, Cladophialophora, Curvularia, Exophiala, Fonsecaea, Phialophora, Wangiella JAAD 80:869–880, 2019 Proteus mirabilis Pseudallescheria boydii – ecthyma gangrenosum Bone Marrow Transplant 27:1311–1313, 2001

BULLAE IN NEWBORN  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSFUNCTION Bullous pemphigoid Clin Exp Dermatol 8:329–332, 1983

Pseudomonas aeruginosa – ecthyma gangrenosum Arch Pediatr 13:S13–16, 2006; JAAD 11:781–787, 1984; Arch Int Med 128:591– 595, 1971; Am J Med 25:877–889, 1958; Arch Dermatol Syphilol 22:655–680, 1930; Wien Klin Wochenschr 10:1093–1101, 1897; JAMA 29:213–216, 1897; neonatal infection

Combined immunodeficiency – desquamative erythematous, morbilliform, or vesiculopapular eruption of newborn (3 weeks)

Pseudomonas cepacia – ecthyma gangrenosum AD 113:199–202, 1977

Maternal bullous disease – pemphigus vulgaris, pemphigoid gestationis, pemphigus foliaceus

Pseudomonas stutzeri – ecthyma gangrenosum Rev Med Interne 25:315–318, 2004

Pemphigoid gestations (herpes gestations), passively transferred AD 143:1168–1172, 2007

Rat-bite fever – hemorrhagic vesicles of the hands and feet with petechiae JAMADerm 153:707–708, 2017; Clin Microbiol Rev 20:13–22, 2007

Pemphigus foliaceus

Epidermolysis bullosa acquisita AD 147:337–341, 2011 Linear IgA disease Curr Opin Ped 28:500–506, 2016; Ped Derm 29:610–613, 2012

Salmonella enteritidis NYS Jnl Med 81:1639–1641, 1981

Pemphigus vulgaris, passively transferred from maternal bullous disease – blisters and erosions Ped Derm 25:97–98, 2008; BJD 157:193–194, 2007; JAAD 55:S113–114, 2006; Ped Derm 23:124–127, 2006; Clin Dermatol 1:42–71, 1983; neonatal pemphigus vulgaris JAMADermatol 150:1223–1224, 2014

Scedosporium – bullous necrotic purpura Ann DV 125:711–714, 1998; Scedosporium apiospermum – septic hemorrhagic necrotic bullae Cutis 84:275–278, 2009

CONGENITAL LESIONS

Scytalidium dimidiatum – ecthyma gangrenosum Eur J Clin Microbiol Infec Dis 12:118–121, 1993

Aplasia cutis congenita, membranous bulla of the scalp AD 137:45–50, 2001; aplasia cutis congenita and epidermolysis bullosa

Rhizopus azygosporus BJD 153:428–430, 2005 Rocky Mountain spotted fever

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(Bart’s syndrome Fetal Ped Pathol 38:72–79, 2019; J Med Chir Pharm 26:556–557, 1767 Bullous dermolysis of the newborn (form of autosomal dominant epidermolysis bullosa or dystrophic epidermolysis bullosa) – hypopigmented patches; giant bullae of the hand and foot; erosions, tongue erosions, milia Ped Derm 34:308–314, 2017; Clin Exp Dermatol 39:550–552, 2014; Ped Derm 30:736–740, 2013; with pseudosyndactyly – mutation in COL7A1; subtype of dystrophic epidermolysis bullosa BJD 157:179–182, 2007; AD 121:1429–1438, 1985 Congenital absence of skin Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of the trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis JAAD 69:909–915, 2013; Ped Derm 29:756–758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985; most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails Ped Derm 30:387-388, 2013; JAAD 58:S104–106, 2008; JAAD 32:873–7, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985   Differential diagnosis:   Aplasia cutis congenita   Amniotic adhesions   Cutaneous trauma   Epidermolysis bullosa   Focal dermal hypoplasia   Intrauterine infection   Intrauterine or perinatal trauma Meningeal heterotopia (ectopic rests of meningeal tissue that have lost central nervous system connection) and rudimentary or atretic meningoceles – exophytic nodular or cystic mass of occipital or parietal scalp – normal skin; glistening or bullous appearance, alopecia, hair collar Ped Derm 32:161–170, 2015 Necrotizing enterocolitis Afr J Ped Surg 10:292–293, 2013 Rudimentary meningocele – bulla of the scalp AD 137:45–50, 2001 Transient bullous dermatosis of the newborn J Cut Pathol 18:328– 332, 1991

INFECTIONS AND INFESTATIONS Bullous impetigo Candidiasis – congenital cutaneous candidiasis – bullae, maculovesicular eruption JAAD 37:817–823, 1997; AJDC 135:273–275, 1981; congenital candidiasis – neonatal papules and vesicles; pneumonia Cutis 93:229–232, 2014; congenital cutaneous candidiasis – bullae, maculovesicular eruption JAAD 37:817–823, 1997; AJDC 135:273–275, 1981 Cytomegalovirus infection AD 148:770–772, 2012 Group B streptococcal infections Herpes simplex, intrauterine Herpes zoster Mucormycosis Indian J Pathol Microbiol 61:103–105, 2018 Pseudomonas infections – hemorrhagic bullae Staphylococcal scalded skin syndrome Zentralseit Kinderheilkd 2:3–23, 1878 Syphilis, congenital; bullae of the scalp and lower legs Clin Infect Dis 46:451–452,472–473, 2008; congenital syphilis – string of pearl blisters Ped Derm 36:735–736, 2019 Varicella – fetal varicella syndrome

INFILTRATIVE DISORDERS Mastocytosis – congenital diffuse cutaneous mastocytosis – neonatal bullous erythroderma Ped Derm 35:525–527, 2018; Ped Derm 28:542–546, 2011

INFLAMMATORY DISORDERS Toxic epidermal necrolysis

METABOLIC DISORDERS Acrodermatitis enteropathica Miliaria crystallina JAAD 47:S270–272, 2002 Porphyrias – congenital erythropoietic porphyria (Gunther’s disease) Ped Derm 28:416–420, 2011; erythropoietic protoporphyria, hepatoerythropoietic porphyria, congenital erythropoietic porphyria, harderoporphyria; erythropoietic porphyria, congenital

PHOTOSENSITIVITY DISORDERS Photosensitive blistering in neonates: Ped Derm 28:416–420, 2011   Congenital erythropoietic porphyria   Hepatoerythropoietic porphyria   Kindler’s syndrome – blisters of the dorsal hand  Transient neonatal porphyrinemia – due to hemolytic disease Ped Derm 35:e272–275, 2018   Xeroderma pigmentosum

NEOPLASTIC DISORDERS Transient myeloproliferative disorder in trisomy 21 – vesiculopustular eruption Ped Derm 28:189–190, 2011

PRIMARY CUTANEOUS DISEASES Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) Rook pp. 1505–1507, 1998, Sixth Edition Epidermolysis bullosa – all types; Herlitz type – uniparental disomy Ped Derm 22:482–487, 2005; Epidermolysis bullosa – Third International Consensus Meeting JAAD 58:931–950, 2008   Epidermolysis bullosa simplex   EBS, localized   EBS, Dowling-Meara    EBS, associated with muscular dystrophy    EBS, autosomal recessive   EBS superficialis    EBS, lethal acantholytic    EBS, associated with pyloric stenosis   Junctional epidermolysis bullosa   JEB, Herlitz   JEB, non-Herlitz    JEB, associated with pyloric atresia   Dominant dystrophic epidermolysis bullosa   DDEB, generalized    DDEB – bullous dermolysis of the newborn   Recessive dystrophic epidermolysis bullosa    RDEB, severe generalized    RDEB, generalized other    RDEB – bullous dermolysis of the newborn   RDEB – inversa recessive dystrophic epidermolysis bullosa – generalized blisters in neonates BJD 164:1104– 1106, 2011

Bullae in Infants and Children Ichthyosis bullosa of Siemens, bullous – superficial flaccid bullae in infancy AD 146:191–196, 2010; BJD 140:689–695, 1999; Arch Dermatol Syph (Berlin) 6:590–608, 1937

SYNDROMES Absent dermal ridges and congenital milia syndrome – multiple bullae of the fingertips and soles AEC syndrome APLAID (autoinflammation and PLAID) – sinopulmonary infections, interstitial pneumonitis, eye inflammation, colitis, arthralgias; epidermolysis bullosa-like eruptions in infancy with vesiculopustular lesions and red plaques JAAD 73:367–381, 2015 Basan syndrome (ectodermal dysplasia) – autosomal dominant; congenital facial milia, nail dystrophy, progressive palmoplantar callosities, absent dermatoglyphics; transient neonatal acral bullae Ped Derm 29:684–685, 2012; Ped Derm 29:527–529, 2012; JAAD 32:315–318, 1995 Down’s syndrome – with transient myeloproliferative disorder (leukemoid reactions) – neonatal pustules, vesicles, papulovesicles Ped Derm 20:232–237, 2003 Focal dermal hypoplasia (Goltz’s syndrome) Generalized mottled pigmentation with postnatal blistering JAAD 50:S65–69, 2004; Arch fur Dermatolgie und Syphilis 139:80–112, 1922 Incontinentia pigmenti AD 139:1163–1170, 2003 Kindler’s syndrome – acral blistering on dorsal aspects of the hands and feet at birth; progressive poikiloderma; atrophy of the hands and feet, photosensitivity BJD 160:1119–1122, 2009; AD 142:1619– 1624, 2006; AD 142:620–624, 2006; AD 140:939–944, 2004; AD 132:1487–1490, 1996; AD 133:1111–1117, 1997; Ped Derm 6:82–90, 1989

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BULLAE IN INFANTS AND CHILDREN  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis Bullous pemphigoid Ped Derm 25:462–465, 2008; JAAD 57:1084– 1089, 2007; Ped Derm 21:160–163, 2004; Ped Derm 19:119–121, 2002; AD 136:527–532, 2000; Ped Derm 15:108–111, 1998; Int J Derm 30:339–342, 1991; bullae of the face, arms, hands, and feet, including palms and soles, in infancy Ped Derm 33:557–558, 2016; JAAD 58:41–48, 2008; AD 143:215–220, 2007; in association with hyper-IgE syndrome Ped Derm 25:28–33, 2008; bullous pemphigoid in infancy – urticarial and bullae BJD 66:1140–1142, 2012; urticaria and bullae in a 3-month-old infant BJD 169:191–192, 2013; bullae of the hands and feet of infant Ped Derm 30:135–136, 2013 Postvaccination bullous pemphigoid in infancy – bullae and urticarial papules Ped Derm 30:741–744, 2013 Chronic bullous disease of childhood (linear IgA disease) Ped Derm 29:529–532, 2012 Cicatricial pemphigoid Combined immunodeficiency – desquamative erythematous, morbilliform, or vesiculopapular eruption of newborn (3 weeks) Dermatitis herpetiformis – hemorrhagic bullae of the palms and soles Ped Derm 11:319–322, 1994 Epidermolysis bullosa acquisita Ped Derm 29:614–617, 2012; JAAD 47:169–187, 2002 Fogo selvagem (endemic pemphigus) JID 107:68–75, 1996; JAAD 32:949–956, 1995 Herpes gestationis – due to transplacental transmission of antibodies AD 112:1129–1131, 1976

Lipoid proteinosis BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002

IgA-mediated epidermolysis bullosa acquisita JAAD 54:734–736, 2006

TRAUMA

Linear IgA disease Ped Derm 26:28–33, 2009; Ped Derm 23:443– 447, 2006; JAAD 47:169–187, 2002; bullae of helices of the ears Ped Derm 28:471–473, 2011; bullae of the face Ped Derm 29:111–112, 2012

Burns, thermal or chemical Sucking blisters – on radial or ulnar side of the wrist; lips Eur J Ped 172:1423–1424, 2013

VASCULAR DISORDERS Lymphangioma Vacuum-assisted delivery – vesicular eruption Ped Derm 31:381– 382, 2014 Volkmann ischemic contracture – cutaneous ulcer with white necrosis of the forearm in newborn; serpiginous border; muscle necrosis and nerve palsy due to increased intracompartmental pressure from amniotic band, oligohydramnios, or abnormal fetal position; begins as large bulla Ped Derm 37:207–208, 2020   Differential diagnosis includes:    Aplasia cutis congenita   Protein C or S deficiency with disseminated intravascular coagulation    Neonatal ecthyma gangrenosum from bacterial infection   Aspergillosis    Varicella-zoster virus infection

IgA pemphigus – neonatal vesicopustules in a 1-month-old JAAD 48:S22–24, 2003

Lupus erythematosus, bullous Cutis 89:17–21, 2012; JAAD 47:169–187, 2002 Pemphigus foliaceus AD 131:1308–1311, 1995; neonatal JAAD 49:S187–189, 2003; JAAD 43:1130–1134, 2000 Pemphigus vulgaris, neonatal – due to transplacental transmission of antibodies JAAD 48:623–625, 2003; BJD 147:801–805, 2002; Ped Derm 3:468–472, 1986

CONGENITAL LESIONS Aplasia cutis congenita – bulla of the scalp JAAD 48:S95–98, 2003; AD 137:45–50, 2001 Congenital absence of skin Congenital erosive dermatosis with reticulated supple scarring – most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985

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Rudimentary meningocele – bulla of the scalp AD 137:45–50, 2001 Transient bullous dermolysis of the newborn with pseudosyndactyly – mutation in COL7A1; subtype of dystrophic epidermolysis bullosa BJD 157:179–182, 2007; AD 121:1429–1438, 1985

Herpes simplex virus – intrauterine infection; neonatal – face and scalp Textbook of Neonatal Dermatology, p. 202, 2001; eczema herpeticum J Infect Dis 158:109–116, 1988; Pediatrics 66:489–494, 1980 Herpes zoster

Transillumination unit – thermal burn

Impetigo, bullous JAAD 47:169–187, 2002; giant bullae due to hypersensitivity to mosquito bites in patients with Epstein-Barr virus infection JAAD 72:1–19, 2015

DRUGS

Meningococcemia

Chemotherapy for acute lymphoblastic leukemia – porphyria cutanea tarda J Drugs Dermatol 13:489–490, 2014

Necrotizing fasciitis – bullae, purpura, lakes of pus, necrosis Ann Surg 199:101–103, 1984

Fixed drug eruptions

Pseudomonas aeruginosa infection

Methotrexate – bullous acral erythema JAAD 52:S93–95, 2005

Rat-bite fever

EXOGENOUS AGENTS

Scabies palmar and plantar bullae in infancy JAAD 82:533–548, 2020; Ped Derm 15:108–111, 1998; JAMA 230:878, 1974 Smallpox NEJM 372:954–962, 2015

Alcohol burn of premature infant Chenopodium album (lamb’s-quarters, white goosefoot) – red face with bullae Ped Derm 28:674–676, 2011 Phototherapy of neonatal jaundice after injection of methylene blue in amniotic cavity – erythema and blistering JAMA 208:1703, 1969 Senneca laxative – blistering erosive diaper dermatitis; diamondshaped erosion of the buttocks with linear borders aligning with diaper edge; spares perianal area and gluteal cleft AD 148:402– 404, 2012; Pediatrics 107:178–179, 2001

INFECTIONS Aspergillus Blistering distal dactylitis – Staphylococcus aureus, Streptococcus pyogenes Candida – congenital cutaneous candidiasis – bullae, maculovesicular eruption JAAD 37:817–823, 1997; AJDC 135:273–275, 1981 Chikungunya fever, congenital – infantile vesicles and bullae Ped Derm 33:264–274, 2016; Ped Derm 33:209–212, 2016; Ped Derm 33:238–240, 2016; Indian Pediatr 49:51–53, 2012 Congenital cytomegalovirus infection Cowpox – tongue ulcer, targetoid and umbilicated indurated papules, vesicles, pustules with central necrosis; exposure to pet rat Clin Inf Dis 68:1063–1064, 2019 Coxsackie A (5, 9, 10, 16) – maculopapular-vesicular; Coxsackie A4 – widespread vesicular eruption Pediatrics 41:873–882, 1968; Coxsackie A16 – hand, foot, and mouth disease; blisters and vesicopustules; perioral dermatitis Cutis 102:353–356, 2018 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of the fingers, palmar erythema, red papules of the ears, red papules of the antecubital fossa, perioral papulovesicles, vesicles of the posterior pharynx; macular purpura of the palms and soles Ped Derm 33:429–437, 2016; JAAD 69:736–741, 2013 Dermatophytosis Ecthyma gangrenosum – anogenital hemorrhagic bulla Ped Derm 36:123–124, 2019 Group B streptococcal infection Hand, foot, and mouth disease (Coxsackie A5, 10, 16) – vesicular; BJD 79:309–317, 1967; Enterovirus 71 Clin Inf Dis 32:236–242, 2001 Hepatitis B virus vaccine – Arthus reaction – vesicles Clin Inf Dis 33:906–908, 2001

Staphylococcal scalded skin syndrome – erythroderma, bullae, erosions BJD 166:213–215, 2012; bullae Ped Derm 27:581, 2010; Zentralseit Kinderheilkd 2:3–23, 1878 Syphilis, congenital – pemphigus syphiliticus Tinea pedis Varicella JAAD 47:169–187, 2002

INFILTRATIVE LESIONS Langerhans cell histiocytosis – varicella-like JAAD 47:169–187, 2002; J Dermatol 21:197–204, 1994; vesicles in newborn JAAD 78:1047–1056, 2018 Mastocytosis, including xanthelasmoidea (diffuse cutaneous mastocytosis) – generalized cutaneous mastocytosis – widespread bullae, including facial bullae JAMADerm 156:212–213, 2020; Ped Derm 28:720–725, 2011; Ped Derm 19:220–223, 2002; AD 138:831–836, 2002; BJD 144:355–358, 2001; urticaria pigmentosa Acta DV (Stockh) 42:433–439, 1962

INFLAMMATORY DISEASES Edematous scarring vasculitic panniculitis – hydroa vacciniformelike lesions with vesicles, deep ulcers, varicelliform scars JAAD 32:37–44, 1995 Erythema multiforme Toxic epidermal necrolysis

METABOLIC DISEASES Acrodermatitis enteropathica – periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche; mutation in SLC39A4 encodes ZIP4 zinc transporter BJD 161:184–186, 2009; JAAD 56:116–124, 2008; Ped Derm 19:426–431, 2002; bullae of the toes (acquired zinc deficiency) AD 145:829–834, 2009 Diabetic bullae Miliaria crystalline, congenital – generalized vesicular eruption Ped Derm 21:171–173, 2004; JAAD 47:S270–272, 2002 Porphyria, congenital; erythropoietic protoporphyria – vesicles; blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, keratoconjunctivitis, cataracts JAAD 67:1093–1110, 2012; BJD 155:574–581, 2006; Eur J Pediatr

Bullae in Infants and Children 159:719–725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751–766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976; porphyria cutanea tarda following chemotherapy for acute lymphoblastic leukemia J Drugs Dermatol 13:489–491, 2014 Protein C deficiency Pseudoporphyria cutanea tarda

NEOPLASTIC Lymphoma – hydroa vacciniforme-like cutaneous T-cell lymphoma (Epstein-Barr virus-associated lymphoproliferative disorder), Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of the ears, pitted scars, fever JAAD 81:534–540, 2019; JAAD 69:112– 119, 2013; BJD 151:372–380, 2004 Pilomatrixoma – red pink bulla with blue base – bullous pilomatrixoma; activating mutation of beta-catenin Ped Derm 32:735–736, 2015; J Dermato Venereol Leprol 78:484–487, 2012; J Dermatol 24:57–59, 1997   Associations of pilomatrixomas    Familial Sotos syndrome   Kabuki syndrome   Myotonic dystrophy   Rubinstein-Taybi syndrome    Turner’s syndrome Transient myeloproliferative disorder associated with mosaicism for trisomy 21 – pustular, papulovesicular, vesiculopustular rash, facial dermatitis Ped Derm 35:831–832, 2018; JAAD 54:S62–64, 2006; NEJM 348:2557–2566, 2003

PHOTODERMATITIS Photosensitive eruption – transient porphyrinemia in infant with hemolytic disease of newborn Polymorphic light eruption

PRIMARY CUTANEOUS DISEASES Acral peeling – autosomal recessive; acral bullae in infancy; older children get skin peeling; transglutaminase 5 mutation Acropustulosis of infancy Acute parapsoriasis mimicking varicella Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) Ectodermal dysplasia – AEC (Hay-Wells) syndrome Ectodermal dysplasia with plakophilin 1 deficiency Epidermolysis bullosa – Third International Consensus Meeting JAAD 58:931–950, 2008   Epidermolysis bullosa simplex   Epidermolysis bullosa, autosomal recessive – blisters and erosions, mild skin fragility, fatal interstitial lung disease, nephrotic syndrome, sparse fine hair, large dystrophic toenails with distal onycholysis; integrin alpha-B mutation NEJM 366:1508–1514, 2012   Epidermolysis bullosa simplex with ectodermal dysplasia and skin fragility – autosomal recessive; plakophilin 1 mutation    EBS, localized – acral blisters with rare oral involvement

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  EBS, Dowling-Meara – severe generalized, herpetiform blisters, oral involvement    EBS, associated with muscular dystrophy    EBS, autosomal recessive   EBS superficialis    EBS, lethal acantholytic    EBS, associated with pyloric stenosis    EBS with mottled pigmentation   Junctional epidermolysis bullosa   JEB, Herlitz Ped Derm 31:530–532, 2014   JEB, non-Herlitz   JEB, associated with pyloric atresia – severe blistering, often fatal; plectin mutation Int J Dermatol 50:439–442, 2011; Hum Mutat 31:308–316, 2010; Dermatol Clin 28:43–54, 2010   Dominant dystrophic epidermolysis bullosa   DDEB, generalized    DDEB – bullous dermolysis of the newborn   Recessive dystrophic epidermolysis bullosa    RDEB, severe generalized Ped Derm 34:166–171, 2017    RDEB, generalized other    RDEB – bullous dermolysis of the newborn    Multiple variants; EBS of the hands and feet – WeberCockayne; EBS, generalized – Koebner variant – bullae of occiput, back, legs in infants; hands and feet in children; EBS herpetiformis – Dowling-Meara JAAD 28:859–861, 1993; EBS with or without neuromuscular diseases – autosomal recessive; muscular dystrophy, myasthenia gravis, spinal muscular atrophy; possible mental retardation; early death reported AD 125:931–938, 1989; lethal autosomal recessive EBS BJD 113:135–143, 1985; Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 89–117; EB atrophicans generalisata gravis, Herlitz type – extensive blistering and erosions at birth; perioral and nasal exuberant granulation tissue; bulbous fingertips with crusting and erosions Rook pp. 1828–1829, 1998, Sixth Edition; Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 118–134; generalized atrophic benign EB (GABEB) (mitis) – nonlethal junctional – generalized blistering beginning in infancy; atrophic scarring; alopecia of the scalp, eyebrows, eyelashes; COL17A1 mutations (GABEB); enamel hypoplasia BJD 156:861–870, 2007; Dermatologica 152:72–86, 1976; pyloric atresia and junctional epidermolysis bullosa JAAD 36:304–310, 1997; EB pruriginosa – mild acral blistering at birth or early childhood; violaceous papular and nodular lesions in linear array on shins, forearms, trunk; lichenified hypertrophic and verrucous plaques in adults BJD 130:617–625, 1994; transient bullous dermolysis of the newborn AD 121:1429–1438, 1985; epidermolysis bullosa simplex with mutation of collagen 17A1 gene; ITGB4 coding for integrin beta4 BJD 151:669–674, 2004; JID 118:185–192, 2002 Epidermolysis bullosa – alpha6-beta4 epidermolysis bullosa – mild blistering and crusting, severe skin fragility, patchy hyperpigmentation of the elbows; onychogryphosis; yellow-brown discoloration of teeth with enamel defects BJD 169:115–124, 2013; autosomal dominant epidermolysis bullosa – acral blisters of the palms and soles and wrists; mutation in ITGB4 JAMADerm 152:558–562, 2016 Erythema toxicum neonatorum JAAD 47:169–187, 2002 Hydroa vacciniforme – vesicles and bullae of the face; association with Epstein-Barr virus JAAD 72:1–19, 2015 Ichthyosis bullosa of Siemens Lethal acantholytic epidermolysis bullosa – autosomal recessive, universal alopecia, cutaneous and mucosal shedding, skin fragility, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010; JID

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130:2680–2683, 2010; BJD 162:138801394, 2010; Dermatol Clin 28:131–135, 2010; mutation in JUP gene Hum Med Genet 20:1811–1819, 2011

Incontinentia pigmenti AD 139:1163–1170, 2003; JAAD 47:169– 187, 2002; palmar and plantar bullae in infancy Ped Derm 15:108– 111, 1998; Curr Prob in Derm VII:143–198, 1995

Miliaria crystallina JAAD 47:S270–272, 2002; Rook p. 455, 1998, Sixth Edition

Kindler’s syndrome – acral bullae in infancy and childhood; progressive poikiloderma with photosensitivity; nail dystrophy, webbing of digits (pseudosyndactyly), esophageal and urethral stenosis, ectropion, poor dentition, periodontitis with gingival fragility and dental caries, dental abnormalities, nail dystrophy, aged hands with fine cigarette paper wrinkling and scarring, hyperkeratosis of the hands and palms and soles (palmoplantar keratoderma), leukoplakia, dyspigmentation, diffuse telangiectasias, short arm chromosome 20; FERMT1 (Kind 1) (fermitin homologue family 1); actin cytoskeleton-extracellular matrix interactions (membraneassociated structural and signaling protein) Ped Derm 37:337–341, 2020; BJD 160:1119–1122, 2009; BJD 160:233–242, 2009; BJD 157:1252–1256, 2007; AD 142:1619–1624, 2006; AD 142:620–624, 2006; BJD 66:104–111, 1954

Pityriasis rosea – cutaneous and intraoral blisters Relapsing annular erythema (neutrophilic figurate erythema of infancy) – facial, polycyclic borders; may be bullous, purpuric, or targetoid Ped Derm 37:209–210, 2020; recurrent annular erythema with purpura – leukocytoclastic vasculitis BJD 135:972–975, 1996; Ann DV 192:457, 2002 Prurigo pigmentosa – initially urticarial papules, then papulovesicles, then vesicles, then crusting or scaling, then reticulated hyperpigmentation; red papules with vesiculation and crusting arranged in reticulated pattern or reticulate plaques in young women; heals with reticulated hyperpigmentation; urticarial red pruritic papules, papulovesicles, vesicles, crusted papules, and plaques with reticulated hyperpigmentation Ped Derm 35:239–241, 2018; JAMADerm 151:796–797, 2015; J Eur Acad Dermatol Venereol 26:1149–1153, 2012; Ped Derm 24:277–279, 2007; JAAD 55:131–136, 2006; Am J Dermatopathol 25:117–129, 2003; Cutis 63:99–102, 1999; JAAD 34:509–11, 1996; AD 130:507–12, 1994; BJD 120:705–708, 1989; AD 125:1551–1554, 1989; JAAD 12:165–169, 1985; J Dermatol 5:61–67, 1978; Jpn J Dermatol 81:78–91, 1971; zosteriform reticulated crusted papules Ped Derm 31:523–525, 2014 Transient bullous dermolysis of the newborn – oral bullae, bullae of newborn Ped Derm 20:535–537, 2003; J Cutan Pathol 18:328–332, 1991; JAAD 21:708–713, 1989; AD 121:1429–1438, 1985

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis Ped Derm 32:604–608, 2015

SYNDROMES

Lipoid proteinosis – vesicles early BJD 148:180–182, 2003 Mendes da Costa syndrome (dystrophia bullosa, typus maculatus) – X-linked recessive; tense bullae, alopecia, coarse reticulated hyperpigmentation of the face and extremities with atrophy, mental retardation Acta DV (Stockh) 18:265, 1937 NOMID syndrome Pachyonychia congenita Peeling skin syndrome Reticulate hyperpigmentation with alopecia, nail changes, and growth retardation with or without blisters Schweiz Med Wochenschr 100:228–233, 1970; Monatsschr Kinderheilkd 78:773–781, 1939 Rothmund-Thomson syndrome – edema, erythema, and blistering of facial skin in infancy which evolves into poikiloderma; sparse scalp hair, eyelashes, and eyebrows; painful focal keratosis of the elbows, knees, palms, and soles Eur J Hum Genet 17:151–158, 2009; Am J Med Genet 102:11–17, 2001 Shabbir’s syndrome (laryngo-onycho-cutaneous syndrome)

Absent dermal ridges and congenital milia syndrome – multiple bullae of the fingertips and soles in neonate

TOXINS

Alagille syndrome – with porphyria cutanea tarda due to retained porphyrins

Laxatives – accidental laxative ingestion in infants; diamond-shaped erythema and bullae; linear borders corresponding to edge of diaper Ped Derm 23:311–320, 2006

Amniotic band syndrome Bloom’s syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; blisters of the nose and cheeks; slender face, prominent nose; facial telangiectatic erythema with involvement of the eyelids, ears, hands, and forearms; bulbar conjunctival telangiectasias; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy; no neurologic deficits Ped Derm 22:147–150, 2005; Curr Prob Derm 14:41–70, 2002; Ped Derm 14:120–124, 1997; JAAD 17:479–488, 1987; AD 114:755–760, 1978; Clin Genet 12:85–96, 1977; Am J Hum Genet 21:196–227, 1969; Am J Dis Child 116:409–413, 1968; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954

TRAUMA Burn, thermal – due to transcutaneous oxygen monitoring Paediatrician 5:335–369, 1976; chemical Child abuse – bullae of the buttocks due to scalding AD 138:318– 320, 2002 Friction blisters Garlic burns Ped Derm 17:475–476, 2000

Ehlers-Danlos syndrome

Sucking blisters, neonatal – fingers, lips, forearms Pediatrics 32:1099–2001, 1963

Generalized mottled pigmentation with postnatal blistering JAAD 50:S65–69, 2004; Arch fur Dermatolgie und Syphilis 139:80–112, 1922

VASCULAR DISEASES

Goltz’s syndrome – neonatal bullae Immuno-osseous dysplasia – short-limbed dwarfism, immunodeficiency, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation) Ped Derm 23:373–377, 2006

Lymphangiectasia (acquired lymphangioma) – due to scarring processes such as recurrent infections, radiotherapy, scrofuloderma, scleroderma, keloids, tumors, tuberculosis, repeated trauma; BJD 132:1014–1016, 1996 Lymphangioma circumscriptum BJD 83:519–527, 1970

Bullae of the Fingers or Toes Lymphedema, congenital (Milroy’s disease) Polyarteritis nodosa – in children; fever, peripheral gangrene, black necrosis, livedo reticularis, ulcers, nodules, vesiculobullous lesions, arthralgia, nodules of the face and extremities, conjunctivitis JAAD 53:724–728, 2005; Ann Rheum Dis 54:134–136, 1995

TRANSIENT BLISTERS IN INFANTS

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Epidermolysis bullosa acquisita – personal observation; IgM epidermolysis bullosa acquisita – bullae of the fingers, elbows, dorsal hands BJD 173:1566–1568, 2015 Graft vs. host disease – bullous scleroderma-like changes AD 121:1189–1192, 1985 Intraepidermal neutrophilic IgA dermatosis (IgA pemphigus) JAAD 31:502–504, 1994 Lupus erythematosus – bullous LE

Congenital self-healing mechanobullous dermatosis

Neonatal linear IgA disease Ped Derm 10:171–176, 1993

Perinatal trauma/iatrogenic injury

Pemphigus vulgaris – neonatal pemphigus Ped Derm 10:169–170, 1993; pemphigus with giant lymph node hyperplasia JAAD 26:105–109, 1992

Self-limited forms of epidermolysis bullosa (Bart’s syndrome) Sucking blisters Transient bullous dermolysis of the newborn Transient maternal autoimmune blistering dermatosis

PAPULOVESICULAR DERMATITIS IN INFANTS

Rheumatoid vasculitis – bullae of the fingertips and toetips with or without purpura; BJD 77:207–210, 1965

DRUG-INDUCED

Behcet’s disease, neonatal

Cabozantinib – VEGFR2 inhibitor; c-met; RET multitargets; tyrosine kinase inhibitor; hand-foot skin reactions with bullae, hyperkeratosis, acral erythema; skin and hair depigmentation, splinter hemorrhages, xerosis, red scrotum JAMADerm 151:170–177, 2015

Congenital candidiasis

Chemotherapy-induced acral erythema Cutis 51:175–179, 1993

Congenital self-healing Langerhans cell histiocytosis JAAD 31:910–6, 1994

Bleomycin – intralesional therapy of warts JAAD 40:367-398, 1999

Eosinophilic pustular folliculitis

Doxycycline – phototoxicity; personal observation

Erythema toxicum neonatorum

Drug-induced pemphigus/penicillamine

Gianotti-Crosti syndrome JAAD 54:136–145, 2006

Epsilon aminocaproic acid infusion JAAD 27:880–882, 1992

Herpes simplex infection

Extravasation from intravenous infusion

Infantile acropustulosis

Fixed drug reaction

Incontinentia pigmenti

Furosemide, in chronic renal failure JAAD 21:1049–1051, 1989

Listeria monocytogenes infection, perinatal

IL-2 reaction AD 130:890–893, 1994

Miliaria

Linear IgA disease  Drug-induced   Amiodarone JAAD 31:809–811, 1994   Ampicillin   Captopril Cutis 44:393–396, 1989   Diclofenac AD 124:1186–1188   Glibenclamide AD 123:1121–1122, 1987   Interferon alpha   Interleukin-2   Iodine   Lithium AD 124:1186–1188, 1988   Penicillin   Vancomycin JAAD 26:45–48, 1992

Absent dermatoglyphics and transient facial milia (vesicles) JAAD 32:315–318, 1995

Transient neonatal pustular melanosis

BULLAE OF THE FINGERS OR TOES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis including nickel sensitivity resembling bullous pemphigoid Anti-epiligrin cicatricial pemphigoid AD 130:1521–1529, 1994 Anti-laminin-gamma-1 (anti-p200) pemphigoid – vesicles and bullae; autoantibody targeting laminin 311 of the lower lamina lucida; strong association with psoriasis J Eur Acad Dermatol Venereol, Sep 29, 2016; JAAD 71:185–191, 2014; BJD 168:1367– 1369, 2013; BJD 168:647–655, 2013; Ann Dermatol Venereol 140:784–787, 2013; BJD 167:1179–1183, 2012; Dermatol 218:265–271, 2009; BJD 158:1354–1357, 2008; J Dermatol 34:1–8, 2007; JID 106:1333, 1996; Med J Rec 130:246–248, 1929

Cantharidin – iatrogenic blisters

Methotrexate and leucovorin (palms and soles) AD 123:990–992, 1987; bullous acral erythema of the toes JAAD 52:S93–95, 2005 Pemphigus vegetans due to captopril JAAD 27:281–284, 1992 Zoonotic orthopoxvirus – teats of cows as source; targetoid bullae of the hands and fingers healing with eschars; edema of the hands; fever; axillary lymphadenopathy NEJM 372:223–230, 2015 Penicillamine AD 128:977–982, 1992

Autoimmune progesterone dermatitis

Penicillamine-induced bullous pemphigoid-like eruption AD 123:1119–1120, 1987

Bullous pemphigoid – periungual blisters; anti-p105 pemphigoid AD 130:343–347, 1994

Penicillin-induced bullous pemphigoid mimicking erythema multiforme JAAD 18:345–349, 1988

Cicatricial pemphigoid – personal observation

Phenacetin-induced bullous pemphigoid-like eruption AD 120:1196– 1199, 1984

Cicatricial pemphigoid-like syndrome due to linear IgA disease directed against a 290 kD antigen JAAD 31:884–888, 1994 Dermatitis herpetiformis Cutis 37:184–187, 1986

Phlebogram dye – toxic reaction Piroxicam photodermatitis

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Pseudo-PCT AD 138:1607–1612, 2002; JAAD 31:500, 1994  Drug-induced   Amiodarone    B complex vitamins   Bumetanide   Chlorthalidone   Ciprofloxacin   Cyclosporine   Dapsone   Etretinate   Finasteride – pseudoporphyria cutanea tarda AD 147:747–748, 2011   Fluoroquinolones   5-Fluorouracil   Furosemide    Hemodialysis in chronic renal failure   Hydrochlorothiazide   Naproxen   Pyridoxine JAAD 14:915–917, 1986   SOMA   Sulfonamides    Tanning bed AD 125:1236–1237, 1989   Tetracycline

vesicles of the posterior pharynx; crusted papules of the scalp, ears, and face; purpuric targetoid painful vesicular lesions of the hands and feet, arthritis, fissured scrotum JAMADerm 149:1419–1421, 2013; JAAD 69:736–741, 2013

PUVA blisters AD 123:1471–1477, 1987

Insect bite reaction

PUVA-induced bullous pemphigoid Cutis 41:199–202, 1988

Leprosy – Lucio’s phenomenon – bullae and necrosis leaving deep painful ulcers Int J Lepr 47:161–166, 1979

Retinoid skin fragility with impetigo

Cytomegalovirus JAAD 18:1330–1338, 1988; JAAD 12:720–721, 1985 Enteroviral infection – vesicular lesions in AIDS Escherichia coli sepsis Gonococcemia – periarticular lesions appear in crops with red macules, papules, vesicles with red halo, pustules, bullae becoming hemorrhagic and necrotic; suppurative arthritis and tenosynovitis Ann Int Med 102:229–243, 1985 Gram-negative web space infection Hand, foot, and mouth disease – Coxsackie A16, A5, A7, A9, A10, B2, B3, B5, enterovirus 7; vesicular Ped Derm 20:52–56, 2003; BJD 79:309–317, 1967 Herpes simplex – dyshidrosis-like herpes simplex in AIDS JAAD 13:845–852, 1985; herpetic whitlow Clin Inf Dis 40:579, 609, 2005; Arch Emerg Med 7:124–125, 1990; herpetic whitlow of the toe Ped Derm 36:406–407, 2019; disseminated herpes simplex infection Herpes zoster

Sorafenib(multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of the feet, hyperkeratotic plaque or blister of the feet, red patches on pressure points, red swollen fingertips, gray blisters of the fingerwebs, angular cheilitis, perianal dermatitis BJD 158:592–596, 2008

Meningococcemia

Tiopronin Ann DV 117:9, 1990

Orf – vesiculopustules of four fingers Cutis 100:148, 158, 2017; AD 126:356–358, 1990

Vasopressin, intravenous JAAD 15:393–398, 1988

Milker’s nodules Necrotizing fasciitis JAAD 20:774–781, 1989 Nocardia asteroides AD 121:898–900, 1985

Papular urticaria Pediculid, bullous Cutis 41:281, 1988

EXOGENOUS AGENTS Acute iododerma from radiocontrast material BJD 170:1377–1379, 2014 Irritant contact dermatitis

Novel poxvirus – equine exposure; targetoid pox-like bullae Clin Inf Dis 60:195–202, 2015 Pseudomonas sepsis Ped Derm 4:18–20, 1987 Rat-bite fever Rheumatoid arthritis – bullae of the fingertips and/or toetips – arteritis BJD 77:207–210, 1965

INFECTIONS AND INFESTATIONS Anthrax – Bacillus anthracis; malignant pustule; face, neck, hands, arms; starts as papule, then evolves into bulla on red base; then hemorrhagic crust with edema and erythema with small vesicles; edema of surrounding skin Am J Dermatopathol 19:79–82, 1997; J Clin Inf Dis 19:1009–1014, 1994; Br J Ophthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981

Scabies – bullous pemphigoid-like eruption JAAD 82:533–548, 2020; JAAD 24:179–181, 1991; non-pruritic bullae Ped Derm 36:552–553, 2019 Snake bites An Trop Med Parasitol 93:401–408, 1999; Am J Trop Hyg 58:22–25, 1998 Staphylococcal sepsis – personal observation

Aspergillosis – primary cutaneous

Syphilis, congenital; vesicular Jarisch-Herxheimer reaction AD 125:77–81, 1989

Bacillus cereus (necrotic bulla) AD 127:543–546, 1991

Tinea manuum, bullous

Blister beetle dermatosis JAAD 22:815–819, 1990; Ped Derm 9:246–250, 1992

Trichosporon beigelii AD 129:1020–1023, 1993

Blistering distal dactylitis (Staphylococcus aureus) JAMADerm 154:1480, 2018; Ped Derm 13:292–293, 1996; AD 118:879–880, 1982; JAAD 5:592–594, 1981

Varicella

Brown recluse spider bite Clin Inf Dis 32:595,636–637, 2001 Bullous impetigo

Vaccinia – progressive vaccinia Verruca vulgaris with secondary infection Vesicular stomatitis virus – vesicles of the fingers, gums, buccal, and pharyngeal mucosa NEJM 277:989–994, 1967

Cat scratch disease (inoculation vesicle) Ped Derm 5:1–9, 1988 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of the fingers, palmar erythema, red papules of the ears, red papules of the antecubital fossa, perioral papulovesicles,

INFILTRATIVE DISEASES Bullous amyloidosis Clin Exp Dermatol 37:788–790, 2012; Cutis 43:346–352, 1989

Bullae of the Fingers or Toes

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Langerhans cell histiocytosis (vesiculopapules) AD 127:1049–1054, 1991

Hydroa vacciniforme AD 114:1193–1196, 1978

Nodular eosinophilic infiltration JAAD 24:352–355, 1991

Phytophotodermatitis – lemon, lime, celery, parsnip, fig tree, carrots, dill, parsley, meadow grass, giant hogweed, wheat, clover, cocklebur, buttercup, shepherd’s purse, pigweed JAAD 67:1093–1110, 2012

Recurrent self-healing cutaneous mucinosis – red papules of the palms and fingertips with pustules and vesicles BJD 143:650–652, 2000

Photoallergic drug reaction

Polymorphic light eruption

INFLAMMATORY DISEASES Eosinophilic pustular folliculitis of the palms and soles

PRIMARY CUTANEOUS DISEASES

Erythema multiforme – personal observation

Acrodermatitis continua

Pyoderma gangrenosum Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988; bullous pyoderma gangrenosum JAAD 27:804– 808, 1992

Anetoderma – bullous appearance of anetoderma overlying a pilomatrixoma JAAD 25:1072–1076, 1991

METABOLIC DISEASES Acrodermatitis enteropathica – tense bullae on all toes; mutation in SLC39A4 encodes ZIP4 zinc transporter BJD 161:184–186, 2009; or acquired zinc deficiency Ped Derm 19:426–431, 2002; bullae of the toes (acquired zinc deficiency) AD 145:829–834, 2009; with anorexia nervosa JAMA 288:2655–2656, 2002 Bullous dermatosis of hemodialysis JAAD 21:1049–1051, 1989 Diabetic bullae Int J Derm 39:196–200, 2000; JAAD 13:799–805, 1985 Bullous gouty tophus NEJM 375:162, 2016 Hypothyroidism with bullae Miliaria crystallina Paroxysmal nocturnal hemoglobinuria AD 122:1327–1330, 1986 Pellagra Porphyria – congenital erythropoietic porphyria BJD 148:160–164, 2003; hepatoerythropoietic porphyria JAAD 11:1103–1111, 1984; porphyria cutanea tarda; variegate porphyria Wien Klin Wochenschr 50:830–831, 1937; BMJ ii:89, 1955 Wilson’s disease – pretibial vesicles with hyperpigmentation JAAD 21:1030–1032, 1989

Carpal tunnel syndrome (necrotic carpal tunnel syndrome) – necrotic fingertips following bullae SkinMed 13:231–232, 2015 Congenital erosive dermatosis with reticulated supple scarring AD 126:544–546, 1990; AD 121:361–367, 1985 Dyshidrotic eczema, including dyshidrotic id reaction Epidermolysis bullosa – simplex, recessive dystrophic AD 133:1111–1117, 1997; epidermolysis bullosa simplex with superficial erosions resembling peeling skin syndrome AD 125:633–638, 1989; EBS herpetiformis – Dowling-Meara – begins in infancy with hemorrhagic blisters of the fingers and toes JAAD 28:859–861, 1993; Kallin’s syndrome – bullae of the hands and feet, nail dystrophy, anodontia, alopecia, deafness Acta DV (Stockh) 65:526–530, 1985; EB atrophicans generalisata gravis, Herlitz type – extensive blistering and erosions at birth; perioral and nasal exuberant granulation tissue; bulbous fingertips with crusting and erosions; Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 118–134; autosomal recessive epidermolysis bullosa with muscular dystrophy or congenital myasthenia gravis AD 125:931–938, 1989; epidermolysis bullosa simplex with mutation of collagen 17A1 gene; ITGB4 coding for integrin beta4 BJD 151:669–674, 2004; JID 118:185–192, 2002 Erythema elevatum diutinum – PCT-like bullae BJD 124:89–91, 1991 Hailey-Hailey disease – pemphigoid-like Hailey-Hailey disease Id reaction Lichen planus, bullous

NEOPLASTIC

Lichen planus pemphigoides JAAD 22:626–631, 1990

Congenital self-healing reticulohistiocytosis AD 126:210–212, 1990

Miliaria

Leukemia – chronic lymphocytic leukemia JAAD 15:943–950, 1986

Pityriasis rosea

Lymphoma – bullous CTCL AD 104:402–406, 1971

Transient bullous dermatosis of infancy JAAD 21:708–713, 1989; AD 129:1209–1210, 1993

Lymphomatoid papulosis – papulovesicles JAAD 38:877–905, 1998 Squamous syringometaplasia of eccrine glands (papulovesicles) AD 129:231–236, 1993 Woringer-Kolopp disease (pagetoid reticulosis) JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939

PSYCHOCUTANEOUS DISEASES Factitial friction blisters Acta DV 55:65–71, 1975

SYNDROMES PARANEOPLASTIC DISEASES

Alagille syndrome

Paraneoplastic pemphigus resembling bullous pemphigoid JAAD 29:815–817, 1993

Amniotic band syndrome

Paraneoplastic scleroderma, edematous phase – personal observation

Behcet’s syndrome JAAD 19:767–779, 1988

PHOTODERMATOSES

Familial Mediterranean fever Cutis 37:290–292, 1986

Celery ingestion with phototoxic burn AD 126:1334–1336, 1990

Bart’s syndrome AD 131:663–668, 1995 Carpal tunnel syndrome – recurrent blistering of the fingertips AD 148:545–546, Glucagonoma syndrome JAAD 30:324–329, 1994

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Goltz’s syndrome Hereditary acral keratotic poikiloderma of Weary Ped Derm 13:427–429, 1996

BULLAE, TRANSIENT, IN INFANTS Bullous pemphigoid

Incontinentia pigmenti

Congenital self-healing mechanobullous dermatosis

Job’s syndrome – vesicles on the face and scalp Ped Derm 5:175–182, 1988

Infants born to mothers with immune-mediated blistering disorders – herpes gestations, pemphigus vulgaris Indian Ped 51:316–317, 2014; pemphigus foliaceus, linear IgA disease JAAD 30:407–411, 1994

Kindler’s syndrome JAAD 6:263–265, 1982 NOMID syndrome Pachyonychia congenita – bullae of the palms and soles JAAD 19:705–711, 1988

Neonatal lupus erythematosus Ped Derm 28:397–400, 2011

Reflex sympathetic dystrophy JAAD 28:29–32, 1993

Perinatal trauma/iatrogenic injury

Rothmund-Thomson syndrome

Self-limited forms of epidermolysis bullosa (Bart’s disease)

Weber-Cockayne syndrome

Sucking blisters

Pemphigoid gestations

Transient bullous dermolysis of the newborn

TOXINS Mustard gas exposure AD 128:775–780, 1992

Transient maternal autoimmune blistering dermatosis Transient porphyrinemia from hemolytic disease in newborn period Ped Derm 35:e272, 275, 2018; JAAD 33:333–336, 1995

Self-defense sprays (orthochlorobenzylidene malononitrile) AD 129:913, 1993

BURNING TONGUE TRAUMA

Anxiety

Chilblains

Burning mouth syndrome J Oral Pathol Med 43:649–655, 2013

Coma blisters Cutis 45:423–426, 1990

Cancerophobia

Cryotherapy or cantharidin for warts

Candidiasis

Erythema ab igne

Contact dermatitis – eugenol Contact Dermatitis 80:54–55, 2019

Fracture blisters JAAD 30:1033–1034, 1994

Drugs

Friction blisters

Fissured tongue JAAD Case Rep 5:923–924, 2019

Frostbite – all fingers and toes NEJM 361:2461, 2009; Hand 15:185–191, 1983

Geographic stomatitis J Clin Exp Dermatol 11:e845–849, 2019

Harpist’s finger Cutis 82:329–334, 2008 Neonatal sucking blisters – on radial forearm, wrist, or hand Cutis 62:16–17, 1998 Nerve injury, traumatic Neurotrophic blisters – neuropathic bullae of the fingers and toes Dermatologica 166:212–214, 1983 Playstation thumb – blisters of thumb S Afr Med J 95:412, 2005; Lancet 363:1080, 2004

Geographic tongue Herpes simplex Herpes zoster Hypertrichosis lanuginosa, acquired Iron deficiency Menopause Nutritional deficiencies (B vitamins) Poor hygiene

Pressure bullae

Squamous cell carcinoma

Pulling boat hands JAAD 12:649–655, 1985

Syphilis, secondary Case Rep Med 2017:1980798

Runner’s blisters – personal observation

Trauma

Thermal burns – personal observation

Vitamin B2 (riboflavin) deficiency Vitamin B12 deficiency

VASCULAR Acantholytic vesicular dermatitis with leukocytoclastic vasculitis JAAD 15:1083–1089, 1986

Xerostomia

BUTTERFLY RASH

Edema bullae – personal observation Congenital lymphedema – Milroy’s disease

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Peripheral vascular disease – vein donor site

Allergic contact dermatitis – personal observation

Reperfusion bullae after cardiac arrest – personal observation

C1q deficiency – atrophic fingers and toes, hypopigmentation, finger tapering, butterfly rash, discoid lupus lesions, Raynaud’s phenomenon; renal disease – segmental mesangiopathic glomerulonephritis; increased interferon 1 levels Ped Derm 33:602–614, 2016

Henoch-Schonlein purpura – personal observation

Acute venous congestion – personal observation

Butterfly Rash

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Dermatomyositis

EXOGENOUS AGENTS

Graft vs. host reaction, acute – malar flush; chronic GVHD – butterfly depigmentation BJD 165:435–437, 2011

Cyprus and geranium products – facial massage; contain furocoumarins NEJM 371:559, 2014

Lupus erythematosus – systemic lupus JAMADerm 155:1417, 2019; Ped Derm 35:808–816, 2018; BJD 170:990–992, 2014; discoid lupus erythematosus Ped Derm 31:113–115, 2014; AD 143:873– 877, 2007; NEJM 269:1155–1161, 1963; neonatal LE NEJM 370:958, 2014; JAAD 40:675–681, 1999; Clin Exp Rheumatol 6:169–172, 1988; systemic lupus

Exogenous ochronosis – personal observation Irritant contact dermatitis Tattoos

Pemphigus erythematosus (Senear-Usher syndrome) JAMADerm 151:1123–1124, 2015; Int J Derm 24:16–25, 1985; JAAD 10:215– 222, 1984; AD 13:761–781, 1926

INFECTIONS AND INFESTATIONS

Pemphigus foliaceus – starts in seborrheic distribution AD 83:52– 70, 1961; pemphigus foliaceus of children – arcuate, circinate, polycyclic lesions AD 148:1173–1178, 2012; JAAD 46:419–422, 2002; Ped Derm 3:459–463, 1986; endemic pemphigus of El Bagre region of Colombia JAAD 49:599–608, 2003

Acute bacterial endocarditis – thrombotic DIC, rheumatic heart disease – personal observation

Pemphigus vulgaris STAT1 gain-of-function mutation – chronic demodicidosis Ped Derm 37:153–155, 2020 STING-associated vasculopathy with onset in infancy (SAVI) – autoinflammatory disease; butterfly telangiectatic facies; red facial plaques, acral atrophic violaceous plaques and acral cyanosis, nodules of the face, nose, and ears; acral violaceous psoriasiform, papulosquamous and atrophic plaques of vasculitis of the hands; distal ulcerative lesions with infarcts, gangrene of the fingers or toes, nasal septal perforation, nail dystrophy; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis; polyarthritis; myositis; gain-of-function mutation in TMEM173 (stimulator of interferon genes) NEJM 371:507–518, 2014 Urticaria

DRUG-INDUCED

AIDS – HIV photosensitivity, seborrheic dermatitis – personal observation

Anaplasmosis – personal observation Candida albicans – chronic mucocutaneous candidiasis; rosacealike eruption AD 142:945–946, 2006 Demodex folliculitis Ped Derm 14:219–220, 1997 Chikungunya fever (Chikungunya virus) – Africa, Middle East, Europe, India, Southeast Asia; fever, arthralgias, morbilliform eruption; polyarthritis and tenosynovitis; hepatitis, myocarditis, hemorrhage, meningitis, encephalitis; palpebral edema; purpuric butterfly eruption of the face; necrosis of skin of the nose Clin Inf Dis 62:78–81, 2016 Crimean-Congo hemorrhagic fever Eur Acad Dermatol Venereol March 21, 2013 Cryptococcosis Clin Inf Dis 56:117, 159–160, 2013 Demodex JAMADerm 150:61–63, 2014 Erysipelas – personal observation Gianotti-Crosti syndrome Herpes simplex – of the face; perianal butterfly rash BJD 147:134– 138, 2002 Impetigo

Chlorpromazine pigmentation

Infectious eczematoid dermatitis

Corticosteroid atrophy and/or telangiectasias – personal observation

Leishmaniasis, including post-kala-azar dermal leishmaniasis – erythema and induration of butterfly region with hypopigmented macules of the trunk and extremities; and infiltrated papules and nodules of the forehead, chin, and central face JAAD 60:897–925, 2009; BJD 157:811–813, 2007; J Coll Phys Surg Pak 17:624–625, 2007; lupoid leishmaniasis Cutis 77:25–28, 2006

Docetaxel-induced recall reaction BJD 153:441–443, 2005 Doxycycline phototoxicity – personal observation Drug hypersensitivity Epidermal growth factor inhibitors – rosacea-like eruption JAAD 55:657–670, 2006 Facial flush due to:    Niacin, nicotinic acid   Nifedipine   Prostacyclin congeners 5-Fluorouracil therapy, systemic or topical Fixed drug eruption Hydroxychloroquine Rheum (Oxford) Oct 23, 2017 Infliximab Mod Rheum 15:223–224, 2005 Lupus erythematosus BJD 165:335–341, 2011   Drug-induced subacute cutaneous lupus erythematosus   Malar rash   Bullous lesions    Vasculitic lesions of the legs    Crusted and necrotic annular and polycyclic lesions

Leprosy – personal observation Lyme disease – malar erythema NEJM 321:586–596, 1989; AD 120:1017–1021, 1984; Borrelia lymphocytoma Am J Dermatopathol 40:216–218, 2018 Measles Mycobacterium tuberculosis – lupus vulgaris Nocardia asteroides BJD 144:639–641, 2001 Papular acrodermatitis of childhood (Gianotti-Crosti syndrome) Parvovirus B19 – erythema infectiosum (fifth disease) Hum Pathol 31:488–497, 2000; J Clin Inf Dis 21:1424–1430, 1995; lupus-like rash Hum Pathol 31:488–497, 2000 Rubella Sporotrichosis – rosacea-like Tinea faciei Cutis 67:7, 2001; tinea incognito Mycoses 49:383–387, 2006

Mycolog rosacea – personal observation

Varicella

Steroid rosacea

Viral exanthem

Tazarotene phototoxicity – personal observation

Yaws

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INFILTRATIVE DISEASES Colloid milium Clin Exp Dermatol 18:347–350, 1993; BJD 125:80– 81, 1991 Jessner’s lymphocytic infiltrate Mastocytosis – telangiectasia macularis eruptiva perstans

INFLAMMATORY DISEASES Eosinophilic pustular folliculitis – annular pustular eruption JAAD 55:285–289, 2006 Erythema multiforme Granuloma annulare, disseminated Kikuchi’s disease (histiocytic necrotizing lymphadenitis) – resembles lupus erythematosus or polymorphic light eruption Lupus 15:384– 387, 2006; Ped Derm 18:403–405, 2001 Lymphocytoma cutis Neutrophilic eccrine hidradenitis – red plaques of the face JAAD 56:693–696, 2007

Lymphoma – angiocentric CTCL of childhood (hydroa-like lymphoma) of Latin America and Asia JAAD 38:574–579, 1998; cutaneous T-cell lymphoma; HTLV-1 lymphoma; lymphoplasmacytoid lymphoma (B-cell lymphoma, immunocytoma) JAAD 49:1159– 1162, 2003 Metastases – metastatic telangiectatic breast carcinoma JAAD Case Rep 2017:3(4)316–318:doi.1016/j.dcr.2017.03.010; JAAD 48:635–636, 2003 Nevus of Ota, bilateral – personal observation Polycythemia vera – suffusion of the face Porokeratosis – porokeratosis ptychotropica – verrucous annular plaques of the buttocks in butterfly distribution JAMADerm 155:845, 2019; Australasian J Derm 58:e149–150, 2017; BJD 132:150–151, 1995 Syringomas

PARANEOPLASTIC DISEASES Necrobiotic xanthogranuloma with paraproteinemia

Neutrophilic sebaceous hidradenitis – persistent malar erythema with atrophy; annular without surface change, photodistributed JAMADerm 154:1215–1216, 2018; JAAD 36:845–846, 1997; AD 129:910–911, 1993

Xanthomas, normolipemic – associated with myeloma

Popsicle panniculitis

Actinic prurigo The Dermatologist May, 2015, pp. 47–48, 50, 2015; BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981

Sarcoid – LE-like and lupus pernio AD 145:905–909, 2009 Stevens-Johnson syndrome – personal observation Whipple’s disease (Tropheryma whipplei) JAAD 60:277–288, 2009

METABOLIC DISEASES Cryoglobulinemia – personal observation Cushing’s syndrome Diabetic rubor Diabetes 14:201–208, 1965 Hartnup disease Homocystinuria – red cheeks JAAD 40:279–281, 1999 Lysinuric protein intolerance – autosomal recessive; defect in membrane transport of cationic amino acids (lysine, arginine, ornithine); hyperammonemia; dermatitis resembling neonatal lupus Lancet 363:1038, 2004; Eur J Pediatr 160:5223, 2001 Melasma Ochronosis – mottled pigmentation of the face Pellagra (niacin deficiency) Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; BJD 125:71–72, 1991

PHOTODERMATOSES

Hydroa vacciniforme – red macules progress to tender papules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars JAAD 42:208–213, 2000; BJD 118:101–108, 1988; Dermatology 189:428–429, 1994; JAAD 25:892–895, 1991; JAAD 25:401–403, 1991; BJD 118:101–108, 1988; AD 118:588–591, 1982; familial BJD 140:124–126, 1999; AD 114:1193–1196, 1978; AD 103:223–224, 1971; late onset BJD 144:874–877, 2001 Kikuchi’s disease – red macules, malar erythema, oral ulcers, photosensitivity, conjunctival injection, lymphadenopathy, fever, arthralgia JAAD 59:130–136, 2008; morbilliform eruption Ped Derm 24:459–460, 2007 Lichen planus actinicus – mimicking melasma JAAD 18:275–278, 1988 Melasma – upper lip, cheeks, forehead, chin BJD 172:1535–1540, 2015; JAAD 65:689–697, 2011; J Drugs in Dermatol 10:517–523, 2011; JAAD 15:894–899, 1986; JAAD 4:698–710, 1981 Phototoxic eruptions

Zinc deficiency

Polymorphic light eruption – papules, plaques, and vesicles BJD 144:446–447, 2001; JID 115:467–470, 2000; JAAD 42:199–207, 2000

NEOPLASTIC DISEASES

PRIMARY CUTANEOUS DISEASES

Angiosarcoma – rosacea-like angiosarcoma JAMADerm 156:587– 588, 2020; indurated red nose JAAD 54:883–885, 2006

Acne rosacea Ophthalmic Vis Res 12:429–433, 2017

Atrial myxoma – red-violet malar flush Cutis 62:275–280, 1998; Br Heart J 36:839, 1994; JAAD 21:1081, 1989

Atopic dermatitis

Diffuse cutaneous reticulohistiocytosis

Epidermolysis bullosa, junctional lethal type (atrophicans generalisata gravis, Herlitz type) – extensive blistering and erosions at birth; perioral and nasal exuberant granulation tissue in butterfly distribution Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 118–134

Pregnancy – hyperpigmentation including melasma

Kaposi’s sarcoma Leukemia – acute myelogenous leukemia Indian J Derm Ven Lep 76:710–712, 2010 Lymphocytoma cutis

Acne vulgaris Darier’s disease

Erythromelanosis follicularis faciei JAAD 32:863–866, 1995

Butterfly Rash Erythrosis pigmentata faciei (erythrose peribuccale pigmentaire of Brocq) Granuloma faciale Granulosis rubra nasi Impetigo herpetiformis Keratosis pilaris Lentiginosis – acquired generalized Ofuji’s disease – eosinophilic pustular folliculitis Dermatology 208:229–230, 2004 Perioral dermatitis Pityriasis rosea Pityriasis rubra pilaris Psoriasis – personal observation

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rosacea Acta DV (Stockh) 41:264–276, 1961; white macules surrounded by erythema and telangiectasia BJD 90:547–551, 1974; pellagrous lesions Am Heart J 47:795–817, 1954 Cockayne syndrome – autosomal recessive; xerosis with rough, dry skin, anhidrosis, erythema of the hands, hypogonadism; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, prematurely aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects, ­demyelination Ped Derm 20:538–540, 2003; Am J Hum Genet 50:677–689, 1992; J Med Genet 18:288–293, 1981 Dubowitz’s syndrome Epidermodysplasia verruciformis with squamous cell carcinoma JAAD 56:882–886, 2007; Arch Dermatol Syphilol 141:193–203, 1922

Seborrheic dermatitis, including AIDS-associated seborrheic dermatitis BJD 111:603–607, 1984

Haber’s syndrome – rosacea-like facial erythema

Ulerythema ophryogenes Vitiligo

Hermansky-Pudlak syndrome – mucocutaneous granulomatous disease in Hermansky-Pudlak syndrome; butterfly red plaques of the face; linear ulcers of the groin and vulva; pink plaques of the thighs; swollen vulva; indurated nodules of the vulva; axillary ulcers, red face JAMADerm 150:1083–1087, 2014

PSYCHOCUTANEOUS DISORDERS

Histiophagocytic syndrome Ann Int Med 114:387–390, 1991

Factitial dermatitis – personal observation

Kindler’s syndrome

Frostbite – personal observation

Reactive arthritis

Urticaria – personal observation

Hartnup disease

Reticular erythematous mucinosis syndrome (REM syndrome)

SYNDROMES Apert’s syndrome – autosomal dominant; FGFR-2 mutation; craniosynostosis with midfacial malformation; cone-shaped calvarium, proptosis, hypertelorism, short nose with bulbous tip; high-arched palate; lips bow-shaped, unable to form a seal; telangiectasias of the face and bulbar conjunctiva, often in butterfly distribution; mottled hyperpigmentation, hypopigmentation and poikiloderma; seborrheic dermatitis, atopic dermatitis, and xerosis common Am J Med Genet 44:82–89, 1992; severe pustular acne at puberty Ped Derm 20:443–446, 2003 Ataxia telangiectasia – telangiectasias in butterfly distribution, of bulbar conjunctivae, tip of the nose, ears, antecubital and popliteal fossae, dorsal hands and feet; atrophy with mottled hypo- and hyperpigmentation, dermatomal CALMs, photosensitivity, canities, acanthosis nigricans, dermatitis; cutaneous granulomas present as papules or nodules, red plaques with atrophy or ulceration JAAD 10:431–438, 1984; Ann Int Med 99:367–379, 1983

Rothmund-Thomson syndrome (poikiloderma congenitale) – autosomal recessive Am J Med Genet 22:102:11–17, 2001; Ped Derm 18:210–212, 2001; Ped Derm 16:59–61, 1999; Dermatol Clin 13:143–150, 1995; JAAD 27:75–762, 1992 Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – butterfly rash, facial dermatitis, exanthema, papules, annular, atypical targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAMADerm 153:461–462, 2017; BJD 142:343–346, 2000; Clin Exp Dermatol 24:74–77, 1999; JAAD 21:374–377, 1989: AD 88:176–180, 1963 SAVI – (STING (stimulator of interferon genes)-associated vasculopathy) – progressive digital necrosis, swelling of the fingers, amputation of several digits, violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of the arms and legs JAAD 74:186–189, 2016 Sjögren’s syndrome – erythema of the nose and cheeks

Bazex syndrome (acrokeratosis paraneoplastica)

Sweet’s syndrome – histiocytoid J Dermatol Sept 25, 2019

Bloom’s syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; slender face, prominent nose; facial telangiectatic erythema with involvement of the eyelids, ears, hands, and forearms; bulbar conjunctival telangiectasias; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy; no neurologic deficits Ped Derm 22:147–150, 2005; Ped Derm 14:120–124, 1997; JAAD 17:479–488, 1987; Am J Hum Genet 21:196–227, 1969; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954

Touraine centrofacial lentiginosis – autosomal dominant, lentigines in butterfly distribution and forehead, central nervous system abnormalities, high forehead, high-arched palate, pectus deformities, kyphosis, spina bifida, umbilical hernias

Carcinoid syndrome – foregut (stomach, lung, pancreas) – bright red geographic flush, sustained, with burning, lacrimation, wheezing, sweating; hindgut (ileal) – patchy, violaceous, intermixed with pallor, short duration edema, telangiectasia, cyanotic nose and face,

BJD 94:39–43, 1976 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial Hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) – Still’s disease-like eruption with erythematous patches, tender red plaques, fever, annular, generalized serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions,

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centrifugal migratory red patch overlying myalgia, red cheeks, morbilliform exanthems; lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia, abdominal pain, headache; Irish and Scottish predominance; mutation in tumor necrosis factor receptor superfamily 1A (TNFRSF1A gene) – gene encoding 55 kDa TNF receptor BJD 161:968–970, 2009; Medicine 81:349–368, 2002; Netherlands Journal of Medicine 59:118–125, 2001; AD 136:1487–1494, 2000; Mayo Clin Proc 62:1095–1100, 1987

VASCULAR DISEASES

Tuberous sclerosis

Mitral stenosis – malar flush

Xeroderma pigmentosum – sunburned infant JAAD 75:855–870, 2016; AD 145:1285–1291, 2009

Primary pulmonary hypertension

Acute hemorrhagic edema of infancy (Finkelstein’s disease) AD 139:531–536, 2003; Cutis 68:127–129, 2001; J Dermatol 28:279– 281, 2001; Cutis 61:283–284, 1998; AD 130:1055–1060, 1994 Emboli – from cardiac myxomas; red-violet malar flush BJD 147:379–382, 2002 Granulomatosis with polyangiitis – mimics acne rosacea BJD 155:221–222, 2006

Superior vena cava obstruction – suffusion of the face Takayasu’s arteritis

TOXINS

Temporal arteritis BJD 76:299–308, 1964

Mercury poisoning – butterfly rash, flushing, perspiration of the face, palmar erythema JAAD 45:966–967, 2001

Vasculitis

Scombroid fish poisoning – facial flush

TRAUMA Air bag dermatitis AD 138:1383–1384, 2002 Post-inflammatory hyperpigmentation secondary to burn Sunburn

Unilateral nevoid telangiectasia, bilateral – personal observation

 AFÉ AU LAIT MACULES (CALMS), C ASSOCIATIONS

retardation, hyperkinesis, failure to thrive, orthopedic anomalies (kyphoscoliosis) Ped Derm 26:97–99, 2009 CHARGE syndrome – café au lait macules with adjacent hypopigmentation (twin spotting) BJD 178:335–349, 2018

Ped Clin N Amer 47:783–812, 2000; JAAD 37:864–869, 1997

CMMR-D syndrome – café au lait macules and widespread lentigines as cutaneous markers for constitutional mismatch repair deficiency; tumors include glioblastoma multiforme, Lynch syndrome (large bowel polyposis), others NEJM 370:2229–2236, 2014

Agminated café au lait macules AKT1 somatic mosaicism – hemihypertrophy, hemimacroglossia, epidermal nevus, café au lait macules BJD 175:612–614, 2016

Congenital diffuse mottling of the skin – mottled pigmentation, café au lait macules, facial lentigines Ped Derm 24:566–570, 2007

Ataxia telangiectasia – café au lait macules may be dermatomal; progeroid appearance with gray hair and skin atrophy; phosphatidylinositol 3-kinase BJD 164:245–256, 2011; BJD 144:369–371, 2001; JAAD 42:939–969, 2000; JAMA 195:746–753, 1966; autosomal recessive; telangiectasias of face, ocular telangiectasia, extensor surfaces of arms and bulbar conjunctiva; hypopigmented macules, melanocytic nevi, facial papulosquamous rash, hypertrichosis, bird-like facies; immunodeficiency, increased risk of leukemia, lymphoma; cerebellar ataxia with eye movement signs, mental retardation, and other neurologic defects; cafe au lait macules JAAD 68:932–936, 2013; Ann Int Med 99:367–379, 1983

Congenital disorders of glycosylation (CDG-I/IIx or III) – depigmented macules, café au lait macules, neurologic abnormalities Ped Derm 22:457–460, 2005 Congenital melanocytic nevus – associated with café au lait macules JAAD 67:495–511, 2012

Bannayan-Riley-Ruvalcaba syndrome – autosomal dominant, macrocephaly, developmental delay, pseudopapilledema, pigmented macules of glans penis, hamartomatous growths including subcutaneous and visceral lipomas, gastrointestinal polyposis, capillary and combined malformations, café au lait macules, testicular enlargement, thyroiditis, hyperextensible joints, pectus excavatum, scoliosis; PTEN mutation JAAD 56:541–564, 2007; Ped Derm 16:77–83,1999

Constitutional mismatch repair deficiency syndrome (CMMR-D) – café au lait macules; hypopigmented macules; hematologic malignancies, rhabdomyosarcoma, brain tumors, early onset gastrointestinal tumors; mutations in MLH1, MSH2, MSH6, OR PMS2 BJD 164:245–256, 2011; Hum Genet 124:105–122, 2008; Eur J Hum Genet 16:62–72, 2008; J Med Genet 46:41803420, 2009 Cowden’s syndrome – café au lait macules; macrocephaly (Lhermite-­Duclos disease – hamartomas of cerebellum, kyphosis, pectus excavatum); keratosis punctate of palms and soles JAAD 68:189–209, 2013; AD 146:337–342, 2010; Ann Intern Med 58:136–142, 1963 Cutis tricolor parvimaculata (twin spotting – didymosis) – small café au lait macules and hypopigmented macules; ring chromosome 15 syndrome; low birth weight, failure to thrive, microcephaly, triangular face, clinodactyly, mental retardation Ped Derm 28:670–673, 2011; Dermatology 211:149–151, 2005

Bloom’s syndrome – large café au lait macules; adjacent areas of hypopigmentation; mutation in DNA helicase BJD 178:335–349, 2018; JAAD 75:855–870, 2016; Curr Prob in Derm VII:143–198, 1995 Café au lait macules with leukemia or glioma – mutations in MLH1 and MSH2 genes Clin in Dermatol 23:56–67, 2005

Darier’s disease Cutis 59:193–195, 1997

CALM and neuroblastoma – autosomal dominant BJD 164:245– 256, 2011

Del (15q) syndrome Am J Med Genet 29:149–154, 1988

CALM and pulmonary stenosis Ann DV 107:313–327, 1980

Dyskeratosis congenita

CALM and ring chromosome 11

Epidermal nevus syndrome Ped Derm 6:316–320, 1989

CALM, temporal dysrhythmia, emotional instability Int J Neuropsychiatry 2:179–187, 1966

FACES (unique facies, anorexia, cachexia, eye, skin lesions) J Craniofac Genet Dev Biol 4:227–231, 1984

Cardio-facio-cutaneous syndrome – autosomal dominant, xerosis/ ichthyosis, eczematous dermatitis, alopecia, growth failure, hyperkeratotic papules, ulerythema ophryogenes (decreased or absent eyebrows), seborrheic dermatitis, CALMs, nevi, hemangiomas, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly scalp hair and sparse eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies with macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of supraorbital ridges, short nose with depressed nasal bridge, high arched palate, low set posteriorly rotated ears with prominent helices, cardiac defects; gain of function sporadic missense mutations in BRAF, KRAS, MEK1, or MEK2, MAP2K1/MAP2K2 BJD 163:881–884, 2010; Ped Derm 27:274–278, 2010; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992

Fair complexions with red or blond hair Ped Derm 33:526–529, 2016

Carney complex – café au lait macules; pigmented nodular adrenocortical disease; thyroid, colon, pancreatic, ovarian carcinoma BJD 164:245–256, 2011 Cerebro-oculo-facial-skeletal syndrome – microcephaly, micrognathia, enlarged ears, bulbous nose, prominent nasal bridge, cataracts, blepharophimosis, short palpebral fissures, mental

Dubowitz syndrome Am J Med Genet 2:275–284, 1978

Familial CALMs – autosomal dominant AD 130:1425–1426, 1994; Curr Probl Cancer 7:1–34, 1982; JAAD 3:157–166, 1980 Familial CALMs – NF type VI Curr Prob in Derm VII:143–198, 1995 Familial hyper- and hypopigmentation – hypopigmentation, hyperpigmentation, lentigines, café au lait macules; mutation in KITLG (kit ligand) BJD 175:1369–1371, 2016 Fanconi’s anemia – autosomal recessive; endocrine abnormalities with hypothyroidism, decreased growth hormone, diabetes mellitus, café au lait macules, diffuse hyperpigmented macules, guttate hypopigmented macules, intertriginous hyperpigmentation, skeletal anomalies (thumb hypoplasia, absent thumbs, radii, carpal bones), oral/genital erythroplasia with development of squamous cell carcinoma, hepatic tumors, microphthalmia, ectopic or horseshoe kidney, broad nose, epicanthal folds, micrognathia, bone marrow failure, acute myelogenous leukemia, solid organ malignancies (brain tumors, Wilms’ tumor) NEJM 370:2229–2236, 2014; BJD 164:245–256, 2011; JAAD 54:1056–1059, 2006;Ped Derm 16:77–83, 1999 Gaucher’s disease BJD 164:245–256, 2011

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Gastro-cutaneous syndrome – peptic ulcer/hiatal hernia, multiple lentigines, café-au-lait macules, hypertelorism, myopia Am J Med Genet 11:161–176, 1982

Mukamel syndrome – autosomal recessive; premature graying in infancy, lentigines, depigmented macules, mental retardation, spastic paraparesis, microcephaly, scoliosis

Hemihyperplasia-Multiple Lipomatosis syndrome – hemihyperplasia at birth, moderate overgrowth, extensive congenital vascular stain (superficial capillary malformation), compressible blue nodule, multiple subcutaneous nodules, hemihypertrophy, hemifacial atrophy, café au lait macules; syndactyly, thickened but not cerebriform soles, ­dermatomyofibroma Ped Derm 31:507–510, 2014; JAAD 56:541–564, 2007; Soc Ped Derm Annual Meeting, July 2005; Am J Med Genet 130A-111–122, 2004; Am J Med Genet 79:311–318, 1998 Hunter’s disease BJD 164:245–256, 2011

Multiple endocrine neoplasia syndrome (MEN I) – autosomal dominant; angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones; meningioma, ependymoma, prolactinoma, gastrinoma, bilateral adrenal hyperplasia AD 148:1317–1322, 2012; JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004; JAAD 42:939–969, 2000; AD 133:853– 857, 1997; Ped Derm 8:124–128, 1991

Jaffe-Campanacci syndrome – coast of Maine CALMs, pigmented nevi and freckle-like macules, fibromas in long bones and jaw, mental retardation, hypogonadism, cryptorchidism, precocious puberty, ocular anomalies, cardiovascular malformations and kyphoscoliosisCurr Prob in Derm VII:143–198, 1995; Clin Orthop Rel Res 168:192–205, 1982

Multiple endocrine neoplasia syndrome (MEN IIA) – cutaneous neuromas, itchy papules of scapulae and amyloid, medullary carcinoma of thyroid, pheochromocytoma, primary hyperparathyroidism; mutation in ret proto-oncogene BJD 164:245–256, 2011; JAAD 42:939–969, 2000; AD 133:853–-857, 1997; Ped Derm 8:124–128, 1991

Johanson-Blizzard syndrome – autosomal recessive; growth retardation, microcephaly, ACC of scalp, sparse hair, hypoplastic ala nasi, CALMs, hypoplastic nipples and areolae, hypothyroidism, sensorineural deafness Clin Genet 14:247–250, 1978

Multiple endocrine neoplasia syndrome (MEN IIB) – Marfanoid habitus, café au lait macules, mucosal neuromas BJD 164:245–256, 2011; JAAD 42:939–969, 2000; AD 133:853–857, 1997; Ped Derm 8:124–128, 1991

Johnson-McMillin syndrome – autosomal dominant, facial nerve palsy, hearing loss, hyposmia, hypogonadism, microtia, alopecia

Neurofibromatosis type I (von Recklinghausen’s syndrome) – café au lait macules, axillary/inguinal freckling, neurofibromas, increased generalized background pigmentation; juvenile xanthogranulomas, glomus tumors, blue-red macules, pseudoatrophic macules, nevus anemicus NEJM 370:2229–2236, 2014; AD 145:883–887, 2009; JAAD 61:1–14, 2009; Dermatol Clinics 13:105–111, 1995; Curr Prob Cancer 7:1–34, 1982; NEJM 305:1617–1627, 1981; giant bathing trunk café au lait macule – type 2 segmental NF1 JAAD 58:493–497, 2008

Juvenile polyposis coli, sporadic juvenile polyps, familial adenomatous polyposis coli Ped Derm 24:350, 2007 Juvenile xanthogranulomas – juvenile chronic myeloid leukemia with familial or sporadic neurofibromatosis Klippel-Trenaunay-Weber syndrome Clin Exp Dermatol 12:12–17, 1987 LEOPARD (Moynahan’s) syndrome – autosomal dominant; CALMs, granular cell myoblastomas, steatocystoma multiplex, small penis, hyperelastic skin, low set ears, short webbed neck, short stature, syndactyly Ped Derm 20:173–175, 2003; JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; J Dermatol 25:341–343, 1998; Am J Med 60:447–456, 1976; AD 107:259–261, 1973; Am J Dis Child 117:652–662, 1969 Leschke’s syndrome – growth retardation, mental retardation, diabetes mellitus, genital hypoplasia, hypothyroidism Lynch syndrome (hereditary non-polyposis colorectal cancer syndrome) J Ped Health Care 34:71–81, 2020 Maffucci’s syndrome JAAD 52:191–195, 2005; Ped Derm 16:77–83, 1999

Neurofibromatosis 1-like phenotype (Legius syndrome) – autosomal dominant; café au lait macules, axillary freckling, and macrocephaly; lipomas, Noonan-like facies; learning and behavioral disorders SPRED1 gene; SPRED-1 protein negatively regulates Ras-mitogen activated protein kinase (MAPK)signaling (like neurofibromin) JAAD 147:735–740, 2011; JAMA 302:2111–2118, 2009; Nat Genet 39:1120–1126, 2007; juvenile myelomonocytic leukemia BJD 164:245–256, 2011 Neurofibromatosis type I-Noonan syndrome Curr Prob in Derm VII:143–198, 1995 Neurofibromatosis type II (central neurofibromatosis) Curr Prob in Derm VII:143–198, 1995 Neurofibromatosis type III (mixed)

Marfan’s syndrome BJD 164:245–256, 2011

Neurofibromatosis type IV (variant)

McCune-Albright syndrome (polyostotic fibrous dysplasia) – giant café au lait macules; triad of fibrous dysplasia of bone (proximal femur and base of skull), café au lait macules and precocious puberty; associated hyperthyroidism, growth hormone excess, renal phosphate wasting with or without rickets, osteomalacia, Cushing’s syndrome; mutation in GNAS (stimulatory G protein) Ped Derm 31:80–82, 2014; Clin in Dermatol 23:56–67, 2005; Ped Derm 8:35–39, 1991; Dermatol Clin 5:193–203, 1987

Neurofibromatosis, segmental – NF type V JAAD 61:1–14, 2009

Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation (nevus depigmentosus); small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008

Niemann-Pick disease – autosomal recessive; sphingomyelinase deficiency

Neurofibromatosis – circumferential, bisegmental – personal observation Neurothekeomas – pink papules on a background of a café au lait macule Ped Derm 28:77–79, 2011 Nevoid basal cell carcinoma syndrome Hered Cancer Clin Pract Oct 29, 2012

Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, prenatal onset short stature, growth retardation, bird-like facies with epicanthal folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of face, café au lait macules,

Cardiac and/or Cardiovascular Disease and Skin Lesions vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair 3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000; Am J Med Genet 66:378–398, 1996 Noonan’s syndrome –with multiple lentigines J Ped Health Care 34:71–81, 2020; NEJM 370:2229–2236, 2014; JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; Curr Prob in Derm VII:143–198, 1995; J Pediatr 66:48–63, 1965 Partial unilateral lentiginosis Patau syndrome (trisomy 13) Peutz- Jegher syndrome BJD 164:245–256, 2011 Phakomatosis pigmentokeratotica – coexistence of CALM, an organoid nevus and a popular speckled lentiginous nevus SkinMed 11:125–128, 2013; Skin and Allergy News, page 34, Sept 2000 Phakomatosis pigmentovascularis type Ia – port wine stain, congenital Becker’s nevus, café au lait macules, and lentigines J Dermatol 26:834–836, 1999 Piebaldism BJD 161:468–469, 2009; Curr Prob in Derm VII:143– 198, 1995 Piebaldism, multiple café au lait macules, and intertriginous freckling – KIT and SPRED1 mutations Ped Derm 30:379–382, 2013

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Tay syndrome – autosomal recessive, growth retardation, triangular face, cirrhosis, trident hands, premature canities, vitiligo Tuberous sclerosis Clin Exp Dermatol 10:562–565, 1985 Turcot syndrome – café au lait macules and intestinal polyposis JAAD 58:902–903, 2008; Clin in Dermatol 23:56–67, 2005 Turner’s syndrome – rare association with NF-1 and tuberous sclerosis Indian J Human Genetics 15:75–77, 2009 Urticaria pigmentosa – simulates cafe au lait macules Verner’s syndrome – café au lait macules and temporal dysrhythmia Von Hippel-Lindau disease – café au lait macules; macular telangiectatic nevi, facial or occipitocervical; retinal angiomatosis, cerebellar or medullary or spinal hemangioblastoma, renal cell carcinoma. pheochromocytoma, café au lait macules Arch Intern Med 136:769–777, 1976 Xanthogranuloma, juvenile BJD 164:245–256, 2011 Watson syndrome – autosomal dominant; intertriginous (axillary and perianal) freckling, CALMs, 1/3 with neurofibromas, Lisch nodules; short stature, intellectual deficit, pulmonary valve stenosis Clin in Dermatol 23:56–67, 2005; JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; Curr Prob in Derm VII:143–198, 1995 Westerhof syndrome – autosomal dominant, hyper- and hypopigmented macules on trunk and extremities, short stature, small sella turcica, cervical ribs AD 114:931–936, 1978

PMS2 defect BJD 178:335–349, 2018 Proteus syndrome – café au lait macules Ped Derm 14:1–5, 1997; port wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, linear and whorled macular pigmentation Am J Med Genet 27:87–97, 1987; Pediatrics 76:984–989, 1985; Eur J Pediatr 140:5–12, 1983 PTEN-hamartoma-tumor syndrome – grossly enlarged hand; recurrent arteriovenous malformations of hand and forearm; macrocephaly, frontal bossing, café au lait macules, congenital nevi, low set ears, downward slanting eyebrows and palpebral fissures Ped Derm 28:466–467, 2011 Ring chromosomes 7, 11, 12, 15, 17 J Ped Health Care 34:71–81, 2020 Ring chromosome 11 – CALMs microcephaly, mental retardation Am J Med Genet 30:911–916, 1988; JAAD 40:877–890, 1999 Ring chromosome 17 – multiple café au lait macules, short stature Ped Derm 22:270–275, 2005 Rubenstein-Taybi syndrome – arciform keloids, hypertrichosis, long eyelashes, thick eyebrows, keratosis pilaris or ulerythema ophryogenes, low set ears, very short stature, broad terminal phalanges of thumbs and great toes, hemangiomas, nevus flammeus, café au lait macules, pilomatrixomas, cardiac anomalies, mental retardation Ped Derm 19:177–179, 2002; Am J Dis Child 105:588–608, 1963 Russell-Silver syndrome – large head, short stature, premature sexual development, CALMs, clinodactyly, syndactyly of toes, small triangular face, ambiguous genitalia, excessive sweating JAAD 40:877–890, 1999; J Med Genet 36:837–842, 1999; Curr Prob in Derm VII:143–198, 1995; Am J Med Genet 35:245–250, 1990 Schimke immuno-osseous dysplasia Eur J Pediatr 159:1–7, 2000 Sporadic, isolated café au lait macules

 ARDIAC AND/OR CARDIOVASCULAR C DISEASE AND SKIN LESIONS JAAD 68:156–166, 2013; NEJM 364:1643–1656, 2011

 UTOIMMUNE DISORDERS AND DISEASES A OF IMMUNE DYSREGULATION Anaphylaxis – cardiovascular collapse Mayo Clin Proc 69:16–23, 1994; exercise-induced Med Sci Sports Exerc 24:849–850, 1992; J Allergy Clin Immunol 75:479–484, 1985; to bacitracin ointment Cutis 83:127–129, 2009; Am J Emerg Med 25:95–96, 2007; J Allergy Clin Immunol 101:136–137, 1998; Am J Contact Derm 6:28–31, 1995; Am J Contact Derm 1:162–164, 1990; AD 120:909–911, 1984; AD 100:450–452, 1969 Dermatomyositis JAMA 305:183–190, 2011 H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; mutation in SLC29A3 gene (equilabrative nucleoside transporter) Ped Derm 33:602–614, 2016 IgG4 disease (sclerosing mesenteritis, sclerodermoid cutaneous changes) – inflammatory periaortitis; coronary arteritis, pericarditis Eur J Radiol 86:169–175, 2017; NEJM 367:2335–2346, 2012 Lupus erythematosus – neonatal lupus erythematosus with RNP antibodies – heart block requiring pacemaker; Libman Sacks endocarditis Ped Derm 30:416–423, 2013 Multiple mitochondrial respiratory chain complex deficiencies – muscle, central nervous system, cardiac, and liver involvement JAMA 312:68–77, 2014

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Scleroderma – left ventricular dysfunction, myocardial fibrosis, arrhythmias Curr Opin Rheum 23:545–554, 2011

pruritus, fever, headaches, arthralgias, neurologic symptoms JAAD 75:19–30, 2016

Still’s disease – pleuropericarditis

Rat bite fever – macular and petechial rash on palms and soles; acral hemorrhagic pustules; palpable purpura; arthritis, pustules; endocarditis, pericarditis, interstitial pneumonia, hepatitis, nephritis, septic arthritis, systemic vasculitis JAMADerm 152:723–724, 2016; J Clin Microbiol 51:1987–1989, 2013; AD 148:1411–1416, 2012; Clin Microbiol Rev 20:13–22, 2007; Clin Inf Dis 43:1585–1586, 1616–1617, 2006; JAAD 38:330–332, 1998

STK4 or Macrophage-stimulating 1 deficiency (MST1) – similar to DOCK 8 deficiency with viral, bacterial, fungal, respiratory infections; cardiac anomalies Dermatol Clinics 35:11–19, 2017

CONGENITAL LESIONS Congenital rubella syndrome – patent ductus arteriosus, pulmonary artery hypoplasia, blueberry muffin baby with cataracts, sensorineural deafness J Maternal Fetal Neonatal Med 30:274–278, 2017

DRUGS All-trans-retinoic acid – Sweet’s syndrome-like neutrophilic panniculitis; solitary red nodule JAAD 56:690—693, 2007; Allretinoic acid syndrome; fever, respiratory distress, weight gain, leg edema, pleural effusions, renal failure, pericardial effusions, hypotension, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum Leuk Lymphoma 44:547–548, 2003

Rheumatic fever – erythema marginatum; abrupt onset polyarthritis, fever in adults; 1/3 adults have no recollection of pharyngitis; spreading erythematous rings (erythema marginatum) of trunk and extremities duration of rash – few hours; pattern changing hourly; carditis; migratory arthritis; dramatic response to salicylates NEJM 369:75–80, 2013; JAAD 8:724–728, 1983; Ann Int Med 11:2223– 2272, 1937–1938 Rocky Mountain spotted fever (Rickettsia rickettsia) NEJM 370:651– 660, 2014 Trichinosis – eosinophilic myocarditis; atrial fibrillation; arrhythmias (most common cause of death); heart block, pericardial effusions Heart 103:651–658, 2017; Clin Inf Dis 59:1750–1756, 2014 Trypanosomiasis

Thalidomide embropathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.370–371

Whipple’s disease(Tropheryma whipplei) – non-palpable purpura, chronic leg edema, arthralgias; large dilated abdominal lymphatics; diarrhea, weight loss, abdominal pain, generalized hyperpigmentation, pulmonary hypertension, eye, cardiovascular, and neurologic disease; blood culture negative endocarditis J Med Case Rep Nov 15, 2015; Clin Infect Dis 41:519–520, 557–559, 2005

EXOGENOUS AGENTS

INFILTRATIVE DISORDERS

Betel nut (areca nut) chewing – betel quid (areca nut, leaf of betel pepper, slaked lime paste from shells, coral, or limestone)autonomic and psychoneurologic effects; cholinergic activation, flushing, tachycardia, warmth, euphoria, alertness, hypotension, angioedema, hyperhidrosis, myocardial infarction Clin Toxicol 39:355– 360, 2001

Amyloidosis – primary systemic amyloidosis; congestive heart failure, purpura; restrictive cardiomyopathy JAAD 77:1145–1158, 2017; NEJM 374:264–274, 2016

DRESS syndrome – acute necrotizing eosinophilic myocarditis, cardiac thrombosis, fibrosis, tachycardia JAAD 66:E229–236, 2012; NEJM 357:2167–2168, 2007; Arch Pathol Lab Med 115:764–769, 1991

Silica dust – occupational scleroderma; digital ulcers, interstitial lung disease, myocardial dysfunction, cancer JAAD 72:456––464, 2015

INFECTIONS AND INFESTATIONS Chagas’ disease (American trypanosomiasis) – megacolon, intestinal perforation; unilateral painful bipalpebral edema, conjunctivitis, local lymphadenopathy, periorbital cellulitis, furuncular lesions (chagomas), panniculitis, myocarditis, inflammatory dilated cardiomyopathy, arrhythmias JAAD 75:19–30, 2016 Endocarditis – acute bacterial endocarditis; subacute bacterial endocarditis with Janeway lesion – faint red macular lesions of thenar and hypothenar eminences Clin Inf Dis 32:63,149, 2001; NEJM 295:1500–1505, 1976; hemorrhagic lesions Med News 75:257–262, 1899; Osler’s node (subacute bacterial endocarditis) – small, red papules on distal finger and toe pads Clin Inf Dis 32:63,149, 2001; NEJM 295:1500–1505, 1976; acute or subacute bacterial endocarditis – acral purpura J Pediatr 120:998–1000, 1992; splinter hemorrhages Br Med J ii:1496–1498, 1963 Erysipeloid (Erysipelothrix rhusiopathiae) – subacute bacterial endocarditis Mansonella perstans – pericardial inflammation, subcutaneous nodules, peritoneal or pleural cavity involvement, angioedema,

Erdheim-Chester disease – pericardial effusion, renal disease, bone pain NEJM 374:470–477, 2016

INFLAMMATORY DISORDERS Ankylosing spondylitis – associated findings include psoriasis, anterior uveitis, inflammatory bowel disease, lung abnormalities, heart conduction defects, aortic insufficiency, renal abnormalities, osteoporosis, vertebral fractures Euro J Intern Med 2011:1–7; Int J Rheumatol 2011:1–10 Eosinophilic myositis/perimyositis – angioedema JAAD 37:385–391, 1997 Sarcoid – cardiomyopathy, ventricular arrhythmias Clin Dermatol 25:203–311, 2007

METABOLIC DISORDERS D-2 hydroxyglutaric aciduria – cardiomyopathy, hypotonia, cortical blindness, macrocephaly Delayed puberty – congenital heart disease Fabry’s disease – biventricular hypertrophy NEJM 368:1732–1738, 2013; Am J Cardiol 106:1492–1499, 2010; angiokeratoma corporis diffusum (alpha galactosidase A deficiency) – X-linked recessive; acral areas cyanotic or blanched due to autonomic dysfunction JAAD 74:231–244, 2016; NEJM 276:1163–1167, 1967

Cardiac and/or Cardiovascular Disease and Skin Lesions GM-1 gangliosidosis – X-linked; gingival hypertrophy, macroglossia, coarse facies, micrognathia, loose skin, inguinal hernia, delayed growth, hepatosplenomegaly, neonatal hypotonia, delayed motor development; kyphosis, cardiomyopathy, cherry red dot of retina, paddle shaped ribs JAMADerm 151:1249–1250, 2015 Hemochromatosis JAMA 312:743–744, 2014 Hemophagocytic lymphohistiocytosis syndrome – fever, pancytopenia, lymphadenopathy, hepatomegaly, splenomegaly, neurologic, joint, purpura, kidney, and cardiac involvement, central nervous system dysfunction Eur Rev Med Pharmacol Sci, 16:1414–1424, 2012; Genes Immunol 13:289–298, 2012   Familial HLH – known genetic defects (perforin)   Immune deficiencies   Chediak-Higashi syndrome   Griscelli syndrome    X-linked lymphoproliferative syndrome  Acquired   Infections   Endogenous products   Rheumatic diseases   Neoplasms Homocystinuria – malar rash; livedo reticularis; ectopic lens, severe osteoporosis, codfish vertebrae, pectus deformity, high arched palate, kyphoscoliosis; tissue paper scars, large facial pores, sparse fine hair, dyspigmentation, superficial thrombophlebitis NEJM 315:1879–1890, 2016 Homozygous familial hypercholesterolemia – cutaneous and tendinous xanthomas; severe aortic and coronary atherosclerosis Sem Vasc Med 4:43–50, 2004 Hyperthyroidism – unilateral eyelid edema JAAD 48:617–619, 2003; hyperpigmentation of eyelids (Jellinek’s sign) JAAD 47:438, 2002; BJD 76:126–139, 1964; Grave’s disease – proptosis due to retraction of eyelids Phosphoglucomutase 1 deficiency – autosomal recessive; disorder of glycosylation with impaired glycoprotein production; liver dysfunction, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, cardiac arrest NEJM 370:533–542, 2014 Selenium deficiency – xerosis, alopecia, leukotrichia, leukonychia; pancytopenia, muscle weakness, muscle pain, cardiac arrhythmia, unsteady gait, distal paresthesias JAAD 80:1215–1231, 2019; Nutrition 23:782–787, 2007; Nutrition 12:40–43, 1996

NEOPLASTIC DISORDERS Atrial myxoma – emboli; violaceous, annular and serpiginous lesions BJD 147:379–382, 2002; Cutis 62:275–280, 1998; JAAD 21:1080–1084, 1989; JAAD 32:881–883, 1995; red-violet malar flush Cutis 62:275–280, 1998; Br Heart J 36:839, 1994; JAAD 21:1081, 1989; necrotic lesions Am J Med 62:792–794, 1977; malar flush with erythema and cyanosis of digit – Br M J 36:839–840, 1974; red feet Br Heart J 36:839–840, 1974; serpiginous lesions of distal finger pads Cutis 62:275–280, 1998; Arthr Rheum 23:240– 243, 1980; leg ulcers, acral red papules with claudication JAAD 32:881–883, 1995; tender red fingertip papule JAAD 21:1080–1084, 1989 Carcinoid tumor – severe fibrotic reaction of right sided valves Sem Cardiothoracic Vasc Anaesth 17:21–223, 2013 Essential thrombocythemia JAAD 24:59–63, 1991 Light chain deposition disease – violaceous plaque of chin; involvement of kidneys (nephropathy), liver, heart, lungs, peripheral nerves Hematol Oncol Clin North Am 13:1235–1248, 1999

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PRIMARY CUTANEOUS DISEASES Cutis laxa – fibulin-4 deficiency (EFEMP2); giant aortic aneurysm; arterial aneurysms and stenosis, aortic root dilatation, furrowing of skin of whole body, abnormal recoil, doughy consistency, emphysema, hernias, joint laxity or contractures, pectus excavatum Turk Ped Ars 54:119–124, 2019 Elastosis perforans serpiginosa – pseudoxanthoma elasticum – linear and reticulated yellow papules and plaques AD 124:1559, 1988; JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; pseudoxanthoma elasticum resembling reticulated pigmented disorders BJD 134:1157–1159, 1996; penicillamine-induced pseudoxanthoma elasticum JAAD 30:103–107, 1994; Dermatology 184:12–18, 1992; saltpetre-induced pseudoxanthoma elasticum Acta DV 58:323–327, 1978 Elastosis perforans serpiginosa with pseudoxanthoma elasticumlike changes in Moya-Moya disease (bilateral stenosis and occlusion of basa intracranial vessels and carotid arteries) BJD 153:431–434, 2005 Lethal acantholytic epidermolysis bullosa – universal alopecia, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010 Epidermolysis bullosa – dystrophic, junctional; dilated cardiomyopathy; ventricular dysfunction and aortic dilatation BJD 174:671–673, 2016; Ped Derm 27:238–243, 2010 Partial congenital lipodystrophy – adipose tissue depots variably affected by lipoatrophy or lipohypertrophy, hepatosplenomegaly, cardiomyopathy, features of acromegaly or hypertriglyceridemia Ped Derm 19:267–270, 2002 Progressive cardiomyopathic lentiginosis Ped Derm 1:146–153, 1953 Psoriasis – metabolic syndrome and coronary artery disease Scleredema of Buschke Total congenital lipoatrophy – severe insulin resistance with Type A features, hepatosplenomegaly, cardiomyopathy, features of acromegaly, hypertriglyceridemia, or genital hypertrophy Ped Derm 19:267–270, 2002 Woolly hair – autosomal dominant, autosomal recessive JAAD 59:1–22, 2008; Q J Med 1:331–347, 1907; Trans St Johns Hosp Soc 60:160–177, 1974; symmetrical allotrichia (acquired progressive kinking) Cutis 24:322–324, 1979; woolly hair nevus JAAD 22:377– 381, 1990; woolly hair seen in Noonan’s, cardiofaciocutaneous, Naxos, Carvajal, and skin fragility-woolly hair syndromes JAAD 61:813–818, 2009

SYNDROMES Adams-Oliver syndrome – congenital scalp ACC and amniotic bands with reduction of terminal phalanges of fingers and toes (terminal transverse limb defects); occasionally severe bony defects with absent hands, feet, or lower legs; bony abnormalities of cranium; cutis marmorata telangiectatica congenita, severe growth retardation, aplasia cutis congenita of knee, short palpebral fissures, dilated scalp veins, simple pinnae, skin tags on toes, hemangioma, undescended testes, supernumerary nipples, hypoplastic optic nerve, central nervous system and congenital heart defects Ped Derm 25:115–116, 2008; Ped Derm 24:651– 653, 2007; BJD 157:836–837, 2007; Am J Med Genet 136A:269– 274, 2005; Plast Reconstr Surg 100:1491–1496, 1997; Clin Genet 47:80–84, 1995; Int J Dermatol 32:52–53, 1993; Eur J Pediatr 126:289–295, 1977; JAAD 56:541–564, 2007; J Hered 36:3–7, 1945

200 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Alagille syndrome (arteriohepatic dysplasia) – paucity of interlobular hepatic ducts; autosomal dominant; pruritus and failure to thrive; wispy hair, dysmorphic facies with triangular face, broad forehead, deep-set eyes, mild hypertelorism, straight nasal bridge with saddle nose, small pointed chin, ventricular hypertrophy, pulmonary artery stenosis; xanthomas; supernumerary digital flexion creases of middle phalanges; JAG1 and Notch2 mutations JAAD 58:S9–11, 2008; cutis laxa-like changes with resolution of xanthomas after liver transplantation Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.553; Ped Derm 15:199–202, 1998; follicular hyperkeratosis BJD 138:150–154, 1998; palmar linear plane xanthomas; porphyria cutanea tarda due to retained porphyrins Behcet’s disease – pericarditis, myocarditis, endocarditis with valvular regurgitation; intracardiac thrombosis, coronary arteritis; +/- myocardial infarctions; aneurysms Cardiol J 21:105–114, 2014; Medicine 91:25–34, 2012 Bifid epiglottis syndrome – accessory auricles with preauricular sinus, polycystic kidney disease with intrahepatic biliary dilatation, endocardial cushion defect, polydactyly Ped Int 52:723–728, 2010 Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; onset under 4 years of age; generalized micropapular rash of trunk and extremities infancy (ichthyosiform); translucent skin-colored papules (non-caseating granulomas) of trunk and extremities or dense lichenoid yellow to red-brown papules with grainy surface with anterior or panuveitis, synovitis, symmetric granulomatous polyarthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; exanthema resolves with pitted scars; camptodactyly (flexion contractures of PIP joints); no involvement of lung or hilar nodes; sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathies, interstitial lung disease, nephritis, arterial hypertension, pericarditis, pulmonary embolism, hepatic granulomas, chronic renal failure; activating mutations in NOD2 (nucleotidebinding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) Ped Derm 34:216–218, 2017; Ped Derm 27:69–73, 2010; AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996; J Pediatr 107:689–693, 1985 Bloom’s syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; blisters of nose and cheeks; slender face, prominent nose; facial telangiectatic erythema with involvement of eyelids, ear, hand and forearms; bulbar conjunctival telangiectasias; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy; no neurologic deficits Ped Derm 22:147–150, 2005; Curr Prob Derm 14:41–70, 2002; Ped Derm 14:120–124, 1997; JAAD 17:479–488, 1987; AD 114:755–760, 1978; Clin Genet 12:85–96, 1977; Am J Hum Genet 21:196–227, 1969; Am J Dis Child 116:409–413, 1968; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954 Borrone dermatocardioskeletal syndrome – autosomal recessive or X-linked; gingival hypertrophy, coarse facies, late eruption of teeth, loss of teeth, thick skin, acne conglobata, osteolysis, large joint flexion contractures, short stature, brachydactyly, camptodactyly, mitral valve prolapse, congestive heart failure Ped Derm 18:534– 536, 2001 Café au lait macules and pulmonary stenosis Ann DV 107:313–327, 1980

Ped Derm 22:75–78, 2005; nuchal skin folds, facial dysmorphism, inverted nipples, hypoplastic nails, petechiae and ecchymoses, edema; neurologic, gastrointestinal and genitourinary abnormalities, pericardial effusion, ascites, oligohydramnios Ped Derm 22:457– 460, 2005 Cardio-acro-facial syndrome (Rabenhorst syndrome) – attached earlobes, cardiac lesions, narrow face with high narrow nose Z Kinderheilk 117:109–114, 1974 Cardio-facio-cutaneous syndrome (NS) – autosomal dominant, characteristic facies with thick facial appearance, broad nose, frontal bossing, ulerythema ophryogenes, sparse or absent eyebrows; xerosis/ichthyosis, eczematous dermatitis, alopecia, growth failure, hyperplastic nipples; hyperkeratotic papules, low set ears with linear earlobe creases; (decreased or absent eyebrows), seborrheic dermatitis, 1–2 café au lait macules; increased numbers of melanocytic nevi; hemangiomas, keratosis pilaris, patchy or widespread ichthyosiform eruption, brittle dark, sparse curly scalp hair and sparse eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies with macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of supraorbital ridges, short nose with depressed nasal bridge, high arched palate, low set posteriorly rotated ears with prominent helices, palmoplantar keratoderma; cardiac defects including pulmonic stenosis, hypertrophic cardiomyopathy, congenital heart defects; psychomotor delay, failure to thrive; gain of function sporadic missense mutations in BRAF, KRAS, MEK1, or MEK2, MAP2K1/MAP2K2 (RASopathy) BJD 164:521–529, 2011; BJD 163:881–884, 2010; Ped Derm 27:274–278, 2010; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992 Cardiomyopathy with alopecia and palmoplantar keratoderma – plakoglobin mutation BJD 166:36–45, 2012 Carney complex – cutaneous and cardiac myxomas, palpitations, diastolic murmur and “tumor plop” J Cardiothoracic Surg March 5, 2011; Clin in Dermatol 23:56–67, 2005 Carpenter syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.22 Carvajal syndrome (ectodermal dysplasia/skin fragility syndrome) – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; mutation in PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; curly hair; perianal erythema and erosions; dilated cardiomyopathy of left side associated with mutation in desmoplakin not with plakophilin Ped Derm 32:641–646, 2015; Ped Derm 32:102–108, 2015; BJD 166:36–45, 2012; Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999

CAPK – autosomal recessive; arrhythmogenic right ventricular cardiomyopathy, alopecia, palmoplantar keratoderma; mutation of plakoglobin (JUP); leg ulcers BJD 165:917–921, 2011

Carvajal-like syndrome – blisters, woolly hair, palmoplantar keratoderma, cardiac abnormalities; heterozygotes of DSP (desmoplakin) BJD 166:894–896, 2012; Clin Genet 80:50–58, 2011; J Cutan Pathol 36:553–559, 2009

Carbohydrate deficient glycoprotein (CDG-Ix) syndrome type I – present at birth; lipodystrophy skin, sticky skin (peau d’orange), strabismus, psychomotor delay, floppy, failure to thrive, mental retardation, liver dysfunction, cerebellar ataxia, pericardial effusions

Cat’s eye syndrome – sporadic; CECR2; iris colobomas, imperforate anus with fistulae, down slanting palpebral fissures, congenital heart anomalies Cutis 88:275–278–280, 2012; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.66–67

Cardiac and/or Cardiovascular Disease and Skin Lesions

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CHARGE syndrome – primary lymphedema, short stature, coloboma of the eye, heart anomalies, choanal atresia, somatic and mental retardation, genitourinary abnormalities, ear anomalies Ped Derm 20:247–248, 2003

Erythrokeratoderma-cardiomyopathy syndrome – recurrent infections, wiry or absent hair, dental enamel defects, nail dystrophy, sudden onset congestive heart failure; early death; dominant mutation in desmoplakin

CHILD syndrome – X-linked dominant; linear hyperkeratosis with brownish scaling of fingers and toes AD 142:348–351, 2006; linear hyperkeratotic plaques of feet (unilateral inflammatory ichthyosiform nevus)with spontaneous involution; strawberry-like papillomatous lesions of toes; macrodactyly; ptychotropism, shortening and absence of limbs, short stature; ipsilateral involvement of bones, lung, kidney, heart, brain; epiphyseal stippling (chondrodysplasia punctata); short stature, scoliosis, clefting of hand or foot, hexadactyly; lateralization and mutations in NSDHL gene which encodes 3-beta hydroxysteroid dehydrogenase JAAD 63:1–22, 2010; BJD 161:714–715, 2009

Finlay-Marks syndrome (scalp-ear-nipple syndrome) – nipple or breast hypoplasia or aplasia, aplasia cutis congenita of scalp, cleft lip/palate, cardiac malformations, polydactyly, narrow convex nails

CHIME syndrome – colobomata, heart defects, ichthyosiform dermatosis of the flexures, mental retardation, and ear defects; congenital ichthyosis with islands of sparing; migratory plaques Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002

H syndrome (low height, heart, hallus valgus, hormonal, hypogonadism, hematologic) – atrial-ventricular septal defects, mitral valve prolapse, cardiomegaly; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; starts on feet and legs and progresses upward; hypertrichosis, short stature, facial telangiectasia, gynecomastia, skeletal deformities (camptodactyly of 5th fingers), scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azoospermia, sensorineural hearing loss, hepatosplenomegaly, mental retardation; mutation in nucleoside transporter Hent3 JAAD 70:80–88, 2014; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008

Ped Derm 18:252–254, 2001; J Med Genet 32:465–469, 1995 Cleft lip and palate, abnormal ears, congenital heart defect, skeletal abnormalities Acta Paediatr Scand 70:767–769, 1981 Cleft palate, absent tibiae, preaxial polydactyly of the feet, and congenital heart defect Am J Dis Child 129:714–716, 1975 Contractural arachnodactyly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.144–145 Costello syndrome – pulmonic stenosis and hypertrophic cardiomyopathy; papillomas of nose and perianal regions; palmoplantar keratoderma, redundant skin of face; mild failure to thrive, developmental delay, outgoing personality; associated with rhabdomyosarcoma, neuroblastoma, transitional cell carcinoma Desmoplakin mutations – syndrome of dilated cardiomyopathy with severe left ventricular dysfunction, congenital alopecia, striate palmoplantar keratoderma, nail dystrophy, follicular hyperkeratosis with hyperpigmented plaques of elbows Ped Derm 32:102–108, 2015 DiGeorge’s syndrome (may be same as velocardiofacial syndrome) – autosomal dominant or sporadic; seborrheic dermatitis, atopic dermatitis; developmental defects of 3rd and 4th pharyngeal pouches, congenital thymic aplasia, neonatal tetany due to absence of parathyroids, cardiac anomalies (truncus arteriosus), short philtrum, low-set malformed ears, hypertelorism, increased susceptibility to Candida, viral, and Pneumocystis carinii infections, loss of portion of proximal long arm of chromosome 22 Down’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.90–91 Dyskeratosis congenita – dilated cardiomyopathy JAAD 77:1194– 1196, 2017 Ehlers-Danlos syndrome – joint hypermobility and laxity; hyperextensible skin; tenascin-X deficiency BJD 163:1340–1345, 2010; type VI – blue sclerae, scleral fragility, joint hypermobility, skin hyperextensibility, easy bruising, atrophic scarring, marfanoid habitus, scoliosis, neonatal hypotonia, arterial dissection; Cutis 82:242–248, 2008 Elejalde syndrome Ellis-van Creveld syndrome (chondroplastic dwarf with defective teeth and nails, and polydactyly) – autosomal recessive; chondrodysplasia, polydactyly, peg-shaped teeth or hypodontia, short upper lip bound down by multiple frenulae; nail dystrophy, hair may be normal or sparse and brittle; cardiac defects; ichthyosis, palmoplantar keratoderma Ped Derm 18:485–489, 2001; Ped Derm 18:68–70, 2001; J Med Genet 17:349–356, 1980; Arch Dis Child 15:65–84, 1940

Goldenhar syndrome (oculo-auriculo-vertebral syndrome) – facial hemiatrophy; accessory tragi (preauricular tags); ocular lipodermoids, epibulbar dermoids; multiple vertebral anomalies, gastrointestinal anomalies, microphthalmia, anophthalmia, colobomata, genital anomalies, micrognathia, microtia, cleft lip/palate, hemifacial microsomia, urologic anomalies, cardiac anomalies, pulmonary anomalies Ped Derm 24:657–658, 2007; JAAD 50:S11–13, 2004; aplasia cutis congenita JAAD 50:S11–13, 2004

Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, bilateral single palmar crease, hirsutism, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac anomalies, hypogammaglobulinemia Ped Derm 23:239–242, 2006 HOPP syndrome – hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, lingua plicata, onychogryphosis, ventricular arrhythmias, periodontitis BJD 150:1032–1033, 2004; BJD 147:575–581, 2002 Horner’s syndrome, including congenital Horner’s syndrome – ptosis, miosis, anhidrosis; contralateral unilateral facial flushing JAAD 55:193–208, 2006; J Neurol Neurosurg Psychiatry 53:85–86; Harlequin sign – hemifacial flushing and contralateral hypohidrosis in Horner’s syndrome Ped Derm 23:358–360, 2006 Holt-Oram syndrome (hand-heart syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.438–439 HOPP syndrome – hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, lingua plicata, onychogryphosis, ventricular arrhythmias, periodontitis BJD 150:1032–1033, 2004; BJD 147:575–581, 2002 Hunter’s syndrome (mucopolysaccharidosis IIb) – X-linked recessive; cardiomyopathy, reticulated 2–10mm skin colored papules over scapulae, chest, neck, arms; cobblestoned skin colored papules also of posterior axillary lines, upper arms, forearms, chest, outer thighs; decreased sulfoiduronate sulfatase; skin-colored papules overlying scapulae; linear and reticular patterns; also on shoulder, upper arms and chest, and lateral thighs; rough thickened skin, coarse scalp hair, and hirsutism; short stature, full lips, coarse facies with frontal bossing, macroglossia, clear corneas (unlike Hurler’s syndrome), progressive neurodegeneration, communicating hydrocephalus, valvular and ischemic heart disease, lower respiratory tract infections, adenotonsillar hypertrophy, otitis media, obstructive sleep apnea, diarrhea, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), widely spaced teeth,

202 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 dolichocephaly, deafness, retinal degeneration, inguinal and umbilical hernias hypertelorism, and thick tongue; dysostosis multiplex; hunched shoulders and characteristic posturing; hepatosplenomegaly; upper respiratory infections due to laryngeal or tracheal stenosis; mental retardation; deafness; retinal degeneration and corneal clouding; umbilical and inguinal hernias; thickened heart valves lead to congestive heart failure; iduronate-2-sulfatase deficiency; lysosomal accumulation of heparin sulfate and dermatan sulfate Ped Derm 33:594–601, 2016; BJD 159:249–250, 2008; Ped Derm 21:679–681, 2004; BJD 148:1173–1178, 2003; Clin Exp Dermatol 24:179–182, 1999; AD 134:108–109, 1998; JAAD 39:1013–1015, 1998; Ped Derm 15:370–373, 1998; Am J Med Genet 47:456–457, 1993; Ped Derm 7:150–152, 1990; AD 113:602–605, 1977

effusion; valvular regurgitation; myocardial infarction; sudden cardiac death

Hurler’s syndrome(mucopolysaccharidosis type I-H)– disorder of glycosaminoglycans accumulation; autosomal recessive; coarse facies, macroglossia, short stature, macrocephaly, hepatosplenomegaly, hernias, corneal clouding, vision and hearing loss; cardiac anomalies; respiratory infections; alpha-l-iduronate deficiency Ped Derm 33:594–601, 2016

Loey’s-Dietz syndrome – autosomal dominant; premature and aggressive aortic aneurysms; mutations in transforming growth factor beta receptor genes 1 and 2; widely spaced eyes, bifid uvula, cleft palate, generalized arterial tortuosity; increased signaling of TGF beta and overproduction of collagen, loss of elastin and disarray of elastic fibers AD 147:223–226, 2011

Hutchinson-Gilford progeria syndrome – initial changes include alopecia, sclerodermoid changes of chest and abdomen, prominent superficial veins and dyspigmentation; premature arteriosclerotic disease JAMADerm 150:197–198, 2014 Hypereosinophilic syndrome – lymphocytic HES associated with cardiac endomyocardial fibrosis with restrictive cardiomyopathy Hypertension – splinter hemorrhages JAAD 50:289–292, 2004 Hypertensive ulcer (Martorell’s ulcer) – very painful ulcer of lower lateral leg with livedo at edges Phlebology 3:139–142, 1988; very painful ulcer of lower lateral leg (above lateral malleolus) with livedo at edges BJD 148:388–401, 2003; Phlebology 3:139–142, 1988; Mayo Clin 21:337–346, 1946; J Cardiovasc Surg (Torino) 19:599– 600, 1978 Hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, periodontitis, lingua plicata, ventricular arrhythmias BJD 147:575–581, 2002 Jaffe-Campanacci syndrome – coast of Maine CALMs, pigmented nevi and freckle-like macules, fibromas in long bones and jaw, mental retardation, hypogonadism, cryptorchidism, precocious puberty, ocular anomalies, cardiovascular malformations and kyphoscoliosis Curr Prob in Derm VII:143–198, 1995; Clin Orthop Rel Res 168:192–205, 1982 Kabuki makeup syndrome – pre-auricular dimple/fistula, short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 570–573, 1981 Kaufman-McKusick syndrome – hydrometrocolpos, hydronephrosis, postaxial polydactyly, congenital heart defect, vaginal atresia J Med Genet 36:599–603, 1999; Eur J Pediatr 136:297–305, 1981 Kawasaki’s disease – coronary artery ectasia and aneurysms; myopericarditis; arrhythmias; ischemic heart disease; pericardial

Kearns-Sayre syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.500–501 Legius syndrome Lentiginosis with arterial dissection syndrome NEJM 332:576–579, 1995 Lentigines with cardiocutaneous myxomas Clin in Dermatol 23:56–67, 2005 LEOPARD syndrome – pulmonic stenosis and hypertrophic obstructive cardiomyopathy; ocular hypertelorism, sensorineural hearing loss, short stature; lentigines, café au lait macules; multiple granular cell myoblastomas; hyperelasticity

Lymphedema-distichiasis syndrome – double row of eyelashes; periorbital edema, vertebral abnormalities, spinal arachnoid cysts, congenital heart disease, thoracic duct abnormalities, hemangiomas, cleft palate, microphthalmia, strabismus, ptosis, short stature, webbed neck Ped Derm 19:139–141, 2002; Hum Genet 39:113–6, 1977 Macrocephaly with intracranial arteriovenous shunt Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.34 Mammalian sterile 20-like kinase 1 deficiency (MST1 deficiency) – autosomal recessive; dermatitis, bacterial, viral, candidal infections; structural cardiac anomalies including atrial septal defect, patent foramen ovale, valvular disease JAAD 73:355–364, 2015 Marfan’s syndrome – aortic root dilatation and dissection; FBN1 mutations; wrist and thumb sign; pectus deformity, increased arm spn/height ratio; reduced upper segment/lower segment ratio; yopia, mitral valve prolapse, striae distensae, ectopic lens, facial features: dolichocephaly, downward slant of palpebral fissures, enophthalmos, retrognathia, malar hypoplasia progressive striae JAAD 64:290–295, 2011; Int J Dermatol 28:291–299, 1989 Marfanoid hypermobility syndrome – marked joint hypermobility, cutaneous hyperextensibility, aortic dissection, no easy bruising JAAD 55:S41–45, 2006 Maroteaux-Lamy syndrome (mucopolysaccaridosis type VI) – autosomal recessive; coarse facies; corneal clouding, endocardial fibroelastosis with cardiomyopathy, dysostosis multiplex Ped Derm 33:594–601, 2016 MASS phenotype – myopia, mitral valve prolapse, mild aortic dilatation, skin striae, skeletal involvement Am J Med Genet 62:417–426, 1996 Meckel syndrome – microcephaly, microphthalmia, congenital heart defects, postaxial polydactyly, polycystic kidneys, cleft lip/palate J Med Genet 8:285–290, 1971 MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes; central nervous system abnormalities, neurosensory hearing loss, dermatomyositis, cardiomyopathy JAAD 65:473–491, 2011 MEND – X-linked recessive; hypomorphic mutation of emopamil-­ binding protein; diffuse mild ichthyosis; telecanthus, prominent nasal bridge, low set ears, micrognathia, cleft palate large anterior fontanelle, polydactyly, 2–3 syndactyly, kyphosis, Dandy-Walker malformation, cerebellar hypoplasia, corpus callosal hypoplasia, hydrocephalus, hypotonia, developmental delay, seizures; bilateral

Cardiac and/or Cardiovascular Disease and Skin Lesions cataracts, glaucoma, hypertelorism; cardiac valvular and septal defects, hypoplastic aortic arch; renal malformation, cryptorchidism, hypospadias BJD 166:1309–1313, 2012 Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation; small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Microphthalmia with linear skin defects (MIDAS syndrome) (MLS syndrome, Xp deletion syndrome, Xp 22.3 microdeletion syndrome) – Xp22.3 deletion – X-linked dominant; linear jagged skin defects of scalp, face, neck, and occasionally upper trunk, Blaschkoesque depressed patches of face, pre-auricular ear pit, severe short stature, congenital heart defects, agenesis of the corpus callosum, ambiguous genitalia, nail dystrophy Ped Derm 25:548–552, 2008; Ped Derm 20:153–157, 2003

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including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microphthalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors (fibromas), lymphomesenteric cysts, ovarian and cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism, BJD 182:212–217, 2020; Ped Derm 32:141–142, 2015; BJD 165:30–34, 2011; AD 146:17–19, 2010; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908–912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004 Nevus sebaceus syndrome – PTEN mutation; hemimegalencephaly, dilated right ventricle, macrocephaly; association with Wilms’ tumor J Med Genet 40:e111, 2003

Myotonic dystrophy (Steinert syndrome) type 1 – autosomal dominant; muscular hypotonia, distal weakness of muscles, frontal alopecia, cataract, sensorineural hearing loss, dysarthria, dysphagia, diabetes mellitus, hypothyroidism, cardiac arrhythmias Dtsch Arztebl Int 116:489–496, 2019; J Med Genet 19:341–348, 1982

Noonan’s syndrome – malformed ears, nevi, keloids, transient lymphedema, ulerythema ophyrogenes, keratosis follicularis spinulosa decalvans, joint hyperextensibility, hypertelorism, webbed neck, down slanting of palpebral fissures, keratosis pilaris atrophicans, short stature, chest deformity (pectus carinatum and pectus excavatum), cubitus valgus, radioulnar synostosis, clinobrachydactyly, congenital heart disease including pulmonary valve stenosis, hypertrophic cardiomyopathy; PTPN 11 gene on chromosome 12; gain of function of non-receptor protein tyrosine phosphate SHP-2 or KRAS gene; other genes SOS1, FAF1, FIT1 Ped Derm 24:417–418, 2007; JAAD 46:161–183, 2002; Cutis 67:315–316, 2001; J Med Genet 24:9–13, 1987; J Pediatr 63:468–470, 1963

Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes, congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321–327, 1996

Noonan’s with multiple lentigines syndrome (formerly LEOPARD syndrome) (cardiocutaneous lentiginosis syndrome); neurofibromatosis

Microphthalmia with linear skin defects (MIDAS syndrome) (MLS syndrome, Xp deletion syndrome, Xp 22.3 microdeletion syndrome) – Xp22.3 deletion – X-linked dominant; linear jagged skin defects of scalp, face, neck, and occasionally upper trunk, Blaschkoesque depressed patches of face, linear red atrophic patches (aplasia cutis-like), hyperpigmented Blascko thin facial patches, reticulate skin defects of head and neck, pre-auricular ear pit, severe short stature, congenital heart defects, agenesis of the corpus callosum, ambiguous genitalia, nail dystrophy, microphthalmia, sclerocornea; mutation in holocytochrome c synthase Ped Derm 29:217–218, 2012; Ped Derm 25:548–552, 2008; Ped Derm 20:153–157, 2003; JAAD 44: 612–615, 2001; Am J Med Genet 49:229–234, 1994

Patau’s syndrome (non-mosaic trisomy 13) – parieto-occipital scalp defects, cleft lip/palate, abnormal helices, low set ears, loose skin of posterior neck, simian crease of hand, hyperconvex narrow nails, polydactyly, microcephaly, microphthalmia, severe central nervous system anomalies, congenital heart defects, holoprosencephaly; death in first year Am J Med Genet 143A:1739–1748, 2007; Ped Derm 22:270–275, 2005; heart malformation affecting interventricular septum Ped Derm 27:199, 2010

Morquio syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.124–125 Myhre syndrome – low birth weight, short stature, muscular build, limited joint mobility, cardiac defects, deafness, skeletal abnormalities, facial dysmorphism, thick skin, keratosis pilaris, coarse facies

Naxos disease – autosomal recessive; palmoplantar keratoderma; woolly scalp hair; right ventricular myopathy; plakoglobin mutation; autosomal recessive; arrhythmogenic right ventricular cardiomyopathy JAAD 59:1–22, 2008; Br Heart J 56:321–326, 1986 Naxos-like disease – autosomal recessive; arrhythmogenic right ventricular cardiomyopathy, woolly hair, early-onset g blisters of knees, palms, and soles; xerosis; mutation in desmoplakin JAAD 59:1–22, 2008; palmoplantar keratoderma with woolly hair AD 130:522–524, 1994; rolled and spiraled hairs Acta DV 65:250–254, 1985; PPK, woolly hair, endomyocardial fibrodysplasia TIG 13:229, 1997 Neurofibromatosis type 1 Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – autosomal dominant; cardiac fibromas; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies,

Peeling skin syndrome – type A (non-inflammatory); type B (inflammatory) – autosomal recessive; erythroderma, congenital onset, pruritus, infections; mutation in CDSN (loss of corneodesmin function); lifelong peeling of skin, recurrent skin infections, angioedema, urticaria, and asthma; dilated cardiomyopathy JID 131:779– 781, 2011; Arch Dermatol Res 304:251–255, 2012; Clin Genet 86:383–386, 2014; Ped Derm 19:382–387, 2002 Progeria – myocardial infarction; heart failure Prune belly syndrome (aplastic abdominal musculature syndrome) (Triad syndrome; Eagle-Barrett syndrome, urethral obstruction malformation sequence) – abdominal muscle hypoplasia, urinary tract abnormalities, bilateral cryptorchidism, pulmonary, skeletal, cardiac and gastrointestinal abnormalities; cerebriform appearance of abdomen; loose and wrinkled skin at birth Ped Derm 23:342–345, 2006; J Urol 139:335–337, 1988 Pseudoxanthoma elasticum – “plucked chicken skin” of flexures and inner lower lip; mitral valve prolapse, restrictive cardiomyopathy, accelerated atherosclerosis, calcification of internal elastic laminae of small and medium sized arteries, myocardial infarction, intermittent claudication, renovascular hypertension premature cardiac disease Clin Dermatol 26:243–254, 2008 Rabenhorst syndrome Dev Period Med 18:289–296, 2014

204

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

RASopathies –   Capillary malformation arteriovenous malformation syndrome  Cardiofaciocutaneous syndrome – ichthyosis-like, keratosis pilaris, sparse curly hair, absent eyebrows, ulerythema oophyrogenes, palmoplantar hyperkeratosis  Costello syndrome – autosomal dominant; short stature, hypotonia with joint laxity; lax skin of hands and feet, deep palmoplantar crease; sparse curly hair   Legius syndrome   LEOPARD syndrome   Neurofibromatosis type 1   Noonan syndrome Reactive arthritis syndrome – erosions with marginal erythema; circinate erosions JAAD 59:113–121, 2008; NEJM 309:1606–1615, 1983; Semin Arthritis Rheum 3:253–286, 1974; Dtsch Med Wochenschr 42:1535–1536, 1916 Ritscher-Schinzel syndrome – autosomal recessive; Dandy Walker-like malformation, atrioventricular canal defect, short stature Am J Med Genet 66:378–398, 1996 Rubenstein-Taybi syndrome – arciform keloids, hypertrichosis, long eyelashes, thick eyebrows, keratosis pilaris or ulerythema ophyrogenes, low set ears, very short stature, broad terminal phalanges of thumbs and great toes, hemangiomas, nevus flammeus, café au lait macules, pilomatrixomas, cardiac anomalies, mental retardation Ped Derm 19:177–179, 2002; Am J Dis Child 105:588–608, 1963 Sakati syndrome – patchy alopecia with atrophic skin above ears, submental linear scars, acrocephalopolysyndactyly, short limbs, congenital heart disease, abnormally shaped low-set ears, ear tag, short neck with low hairline J Pediatr 79:104–109, 1971 Scheie syndrome (mucopolysaccaridosis type I) – autosomal recessive; alpha-l-iduronate deficiency; disorder of glycosaminoglycans; corneal clouding, joint stiffness, cardiac valvular disease Ped Derm 33:594–601, 2016 Shokeir syndrome – proportionate short stature, absent thumbs, anosmia, ichthyosiform dermatosis, congenital heart defect Am J Med Genet 66:378–398, 1996 Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes, congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321–327, 1996 Shprintzen-Goldberg syndrome (velo-cardio-facial syndrome) (familial aneurysm syndrome) – craniosynostosis, marfanoid features, aortic root dilatation Pan Afr Med J April 25, 2016 Steatocystoma multiplex – pilar cysts and Tetralogy of Fallot and clinodactyly – characteristic facies, preauricular pits, fifth finger clinodactyly, tetralogy of Fallot Clin Pediatr (Phila)27:451–454, 1988 Storm syndrome – calcific cardiac valvular degeneration with premature aging; Werner-like syndrome Am J Hum Genet 45 (suppl) A67, 1989

Trisomy 13 – total body milia; polydactyly, congenital cystic adenomatoid malformation, pulmonary hypertension, apnea, atrial septal defect, umbilical hernia, epilepsy, dislocated hip joint, ocular hypertelorism, microphthalmia, retinal hypoplasia, irideremia, small ears, deafness, broad flat nose, cleft palate, micrognathia, mental retardation Ped Derm 27:657–658, 2010; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.86–87 Trisomy 18 (Edward’s syndrome) – characteristic craniofacial features, overriding fingers, nail hypoplasia, 75% with major cardiac structural malformations; septal defects, patent ductus arteriosus, polyvalvular disease) Orphane J Rare Dis Oct 23, 2012 Tuberous sclerosis – cardiac rhabdomyoma Indian J Dermatol 50:13–20, 2011 Turner’s syndrome (XO in 80%) – bicuspid aortic valve, aortic coarctation, aortic dissection; peripheral edema at birth which resolves by age 2; redundant neck skin in newborn; cutis laxa of neck and buttocks; small stature, broad shield-shaped chest with widely spaced nipples, arms show wide carrying angle, webbed neck, low posterior hairline, low misshapen ears, high arched palate, short fourth and fifth metacarpals and metatarsals, hypoplastic nails, keloid formation, increased number of nevi; skeletal, ocular abnormalities; increased pituitary gonadotropins with low estrogen levels JAAD 74:231–244, 2016; JAAD 50:767–776, 2004; JAAD 40:877–890, 1999; Ann Med 31:99–105, 1999 Ulnar-mammary syndrome – autosomal dominant; ulnar defects, nipple or apocrine gland hypoplasia; wide face, nasal base and tip, protruding chin; cardiac abnormalities TXB3 mutation Eplasty 27:14:ic35, e collection 2014, 2014 September VACTERL syndrome (vertebral anomalies, anorectal malformations, cardiac defects, tracheo-esophageal fistulae, renal or radial anomalies, limb malformations) – sporadic J Pediatr 93:270–273, 1978 VATER syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.548–549 Watson syndrome – autosomal dominant; intertriginous (axillary and perianal) freckling, CALMs, short stature, intellectual deficit, pulmonary valve stenosis Clin in Dermatol 23:56–67, 2005; JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; Curr Prob in Derm VII:143–198, 1995 Werner’s syndrome (pangeria) – mottled hyperpigmentation; premature arteriosclerotic cardiovascular disease Medicine 45:177–221, 1966 Williams’ syndrome – premature laxity of skin, congenital heart disease (supravalvular aortic stenosis), baggy eyes, full cheeks, prominent lips, dental malocclusion, delayed motor skills, cocktail party personality Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.484–485; J Pediatr 113:318–326, 1988 Wolf-Hirschhorn syndrome – del (4p) syndrome – preauricular tag or dimple, craniofacial asymmetry, mental and growth retardation, eye lesions, cleft lip and palate, cardiac defects Eur J Hum Genet 8:519–526, 2000

Striate PPK with dilated cardiomyopathy and woolly hair – autosomal recessive; focal striate PPK Curr Prob Derm 14:71–116, 2002; epidermolytic palmoplantar keratoderma with woolly hair and dilated cardiomyopathy JAAD 39:418–421, 1998

XXYY syndrome – features of Klinefelter’s; sparse body hair; also multiple angiomas, acrocyanosis, and premature peripheral vascular disease AD 94:695–698, 1966

Thrombocytopenia-absent radius syndrome (TAR) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.374–375

TOXINS

Townes-Brocks syndrome – autosomal dominant; triad of imperforate anus, lop ears associated with sensorineural and/or conductive hearing loss, preauricular tags, and thumb malformations (triphalangeal thumbs, duplication of thumb, or hypoplasia of thumb; renal failure, congenital heart disease, flat feet, genitourinary malformations; SALL1 mutation Gene Reviews (Internet). Seattle (WA), Jan 24, 2007; Dysmorphol Clin Genet 2:104–108, 1988

Arsenic poisoning – cardiovascular symptoms, garlicky odor, severe diarrhea NEJM 370:1542–1550, 2014 Boric acid ingestion – “boiled lobster” erythema with subsequent desquamation; cardiogenic shock, seizures, renal failure Clinical Toxicology 47:432, 2009; Inf Dis in ObGyn 6:191–194, 1998 Fetal alcohol syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.480–483

CELLULITIS IN THE IMMUNOCOMPROMISED HOST

TRAUMA Cardioversion (defibrillation) – hypopigmented, atrophic, telangiectatic, crusted erythematous plaque of back with rim of hyperpigmentation; delayed onset of years AD 145:1411–1414, 2009 Radial artery puncture – splinter hemorrhages JAAD 50:289–292, 2004

VASCULAR DISORDERS Arteriosclerosis AD 138:1296–1298, 2002; arteriosclerosis obliterans in patients with chronic renal failure JAAD 57:322–326, 2007; livedo reticularis punched out ischemic ulcers over pretibial areas or toes BJD 148:388–401, 2003; peripheral vascular disease with foot ulcerations; xerosis as part of distal trophic changes Arteriovenous fistula (between iliac artery and vein) – right heart failure – edema of lower extremities with erythema (venous congestion) NEJM 367:2241–2247, 2012 Buerger’s disease (thromboangiitis obliterans) – splinter hemorrhages JAAD 50:289–292, 2004; leg ulcers) BJD 148:388–401, 2003; AD 134:1019–1024, 1998; Cutis 51:180–182, 1993; Am J Med Sci 136:566–580, 1908; recurrent venous thrombosis with supravenous erythema Am J Med Sci 136:567–580, 1908; necrosis around nails

Parkes-Weber syndrome – arteriovenous malformation with multiple arteriovenous fistulae along extremity with limb (usually leg) overgrowth; arteriovenous shunting; cutaneous red stain; lymphedema; high output congestive heart failure, hypertrophied digits with severe deformity; red foot JAAD 56:541–564, 2007; Curr Prob in Dermatol 13:249–300, 2002; BJD 19:231–235, 1907 Familial mitral valve prolapse syndrome – marfanoid habitus Am J Med Genet 62:417–426, 1996 Moya-Moya disease – narrowing or occlusion of supraclinoid portion of the internal carotid artery and stems of anterior and middle cerebral arteries; livedo reticularis Ped Derm 20:124–127, 2003; elastosis perforans serpiginosa with pseudoxanthoma elasticum-like changes in Moya-Moya disease (bilateral stenosis and occlusion of basal intracranial vessels and carotid arteries) BJD 153:431–434, 2005 PHACES syndrome – coarctation of the aorta; arterial anomalies Sem Cut Med Surg 35:117–123, 2016 Post-reperfusion syndrome – massive edema of muscles; may lead to amputation; peripheral cyanosis, livedo reticularis, edema of foot; myocardial injury, renal failure Int Wound J March 3, 2014; Semin Vasc Surg 22:52–57, 2009; Plast Reconstr Surg 117:1024–1033, 2006 Rapidly involuting congenital hemangioma of the liver – high output cardiac failure Sem Cut Med Surg 35:124–127, 2016

Capillary malformation-arteriovenous malformation syndrome (CM-AVM syndrome) – RASA1 mutation; vascular stains and cardiac failure; multiple capillary malformations, Parkes-Weber syndrome, multiple infantile hemangiomas, pink patches Ped Derm 32:76–84, 201

CDKN2A WITH P14 LOSS

Cardiac failure – livedo reticularis JAAD 52:1009–1019, 2005

Dysplastic nevi and internal malignancies

Cholesterol emboli – acral cyanosis; livedo reticularis; blue toes JAAD 55:786–793, 2006

Nerve sheath tumors

Coarctation of the aorta – cutaneous mottling of arm BJD 148:1066–1068, 2003

Sarcomas

Congestive heart failure – red nails, red lunulae; periorbital edema; right sided congestive heart failure – peripheral edema Am J Med 113:580–586, 2002

BJD 174:800–802, 2016 Brain tumors

Melanoma

Constrictive pericarditis NEJM 333:45–-48, 1995

CELLULITIS IN THE IMMUNOCOMPROMISED HOST

Degos’ disease – pericarditis pleuritis, visual defects, central nervous system signs and symptoms JAMADerm 156:204, 2020

Absidia corymbifera Ann Hematol 87:687–689, 2008

Diffuse neonatal hemangiomatosis and heart failure Acta Ped 102:e232–238, 2013 Eosinophilic granulomatosis with polyangiitis – endomyocardial infiltration, pericarditis, arrhythmia, valvular defects; primary cause of mortality; carditis, cardiomyopathy with chest pain; retiform purpura JAAD 82:783–796, 2020; JAAD 47:209–216, 2002; JAAD 37:199–203, 1997; JAAD 27:821–824, 1992; JID 17:349–359, 1951; Am J Pathol 25:817, 1949 Hepatic hemangiomas associated with multiple cutaneous infantile hemangiomas – congestive heart failure Seminars Cut Med Surg 35:108–116, 2016

205

Acanthamebiasis in AIDS AD 131:1291–1296, 1995 Alternariosis AD 124:1822–1825, 1988; Alternaria chartarum – red, scaly plaque BJD 142:1261–1262, 2000 Anthrax (Bacillus anthracis) Int J Derm 20:203, 1981 Aspergillosis, primary cutaneous JAAD 12:313–318, 1985; JAAD 31:344–347, 1994 Bacillary angiomatosis – plaque with hyperkeratotic center BJD 126:535–541, 1992 Bipolaris hawaiiensis Campylobacter fetus Acta Clin Belg 64:346–348, 2009

Leukonychia – congestive heart failure – Terry’s nails (proximal 80% of nail plate is white, distal 20% is pink) Indian J Dermatol 62:309– 311, 2017

Campylobacter jejuni – erysipelas-like lesions in patient with hypogammaglobulinemia Eur J Clin Microbiol Infect Dis 11:842– 847, 1992

Mitral stenosis – splinter hemorrhages JAAD 50:289–292, 2004; facial rubor

Candidiasis

Morquio syndrome (mucopolysaccharidosis type IV) – autosomal recessive; short neck, skeletal abnormalities, corneal clouding, cardiac valvulopathies, odontoid hypoplasia, hypermobile joints Ped Derm 33:594–601, 2016

Chagas disease (reactivation post-transplant) Cutis 48:37–40, 1991

Candida tropicalis Cutis 93:204–206, 2014 Clostridium septicum Rev Infect Dis 1:13, 1991 Cryptococcosis – cellulitis JAMA 309:1632–1633, 2013; Cutis 72:320–322;2003; J Dermatol 30:405–410, 2003; Clin Inf Dis

206 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 33:700–705, 2001; Australas J Dermatol 38:29–32, 1997; JAAD 32:844–850, 1995; Scand J Infect Dis 26:623–626, 1994; Clin Inf Dis 16:826–827, 1993; Clin Inf Dis 14:666–672, 1992; Int J Dermatol 29:41–44, 1990; JAAD 17:329–332, 1987; Cutis 34:359– 361, 1984

Mycobacterium haemophilum Am J Transplant 2:476–479, 2002; BJD 149:200–202, 2003; JAAD 40:804–806, 1994

Cunninghamella Am J Clin Pathol 80:98, 1983

Mycobacterium szulgai – diffuse cellulitis, nodules, and sinuses Am Rev Respir Dis 115:695–698, 1977

Curvularia Cutis 89:65–68, 2012 Cytomegalovirus Medicina (B Aires)62:572–574, 2002 Dematiaceous fungal infections in organ transplant recipients   Alternaria   Bipolaris hawaiiensis   Exophiala jeanselmei, E. spinifera, E. pisciphera, E. castellani   Exserohilum rostratum   Fonsecaea pedrosoi   Phialophora parasitica

Mycobacterium kansasii – red plaque JAAD 41:854–856, 1999; JAAD 40:359–363, 1999; JAAD 36:497–499, 1997; Cutis 31:87–89, 1983; Am Rev Resp Dis 112:125,1979

Mycobacterium thermoresistible – violaceous indurated plaque Clin Inf Dis 31:816–817, 2000 Mycobacterium tuberculosis Clin Exp Dermatol 25:222–223, 2000 Myiasis – palpebral myiasis presenting as preseptal cellulitis Arch Ophthalmol 116:684, 1998 Morganella morganii Nocardiosis JAAD 23:399–400, 1990; JAAD 13: 125–133, 1985

Dermatobia hominis (myiasis)

Nocardia asteroides AD 121:898–900, 1985

Escherichia coli Clin Pediatr 26:592, 1987

Onchocerciasis

Erysipelothrix insidiosa

Paecilomyces JAAD 37:270–271, 1997; JAAD 35:779–781, 1996;

Fusarium solani – digital cellulitis Transpl Proc 42:599–600, 2010

AD 122:1169, 1986

Group G streptococcus AD 118:934, 1982

Phaeohyphomycosis JAAD 18:1023–1030, 1988

Helicobacter cinaedi World J Gastro 21:7911–7915, 2015; Ann Int Med 121:90, 1994

Phialophora parasitica

Hemophilus influenzae Am J Med 63:449, 1977

Prevotella species J Clin Inf Dis (Suppl 2):S88–93, 1997

Herpes simplex virus

Protothecosis JAAD 31:920–924, 1994; AD 125:1249–1252, 1989; cellulitis Cutis 63:185–188, 1999; JAAD 32:758, 1995; BJD 146:688–693, 2002

Herpes zoster Histoplasmosis – cellulitis AD 118:3–4, 1982; S Med J 74:635–637, 1981; AD 95:345–350, 1967; panniculitis AD 132:341–346, 1996; JAAD 25:912–914, 1991; JAAD 25:418–422, 1991; Medicine 60:361–373, 1990; AD 118:3–4, 1982 IL-1 receptor-associated kinase 4 gene (IRAK-4) mutations – cellulitis, abscesses, impetigo JAAD 54:951–983, 2006; Science 299:2076–2079, 2003 Klebsiella pneumonia – grossly swollen thigh with focal ulcerations, crepitus, fever, impaired state of consciousness Clin Inf Dis 56:1457,1505–1506, 2013

Phlegmon

Pseudallescheria boydii JAAD 21:167–179, 1989 Pseudomonas aeruginosa JAMA 248:2156, 1982 Rhizopus oryzae Mycopathologia 182:387–392, 2017 Rhizopus pusillus Transpl Infect Dis 21:e13039, 2019; Arch Surg 111:532, 1976 Scedosporium Acute Med 15:88–91, 2016 Serratia marcescens – cellulitis JAAD 49:S193–194, 2003; JAMA 250:2348, 1983

Legionella micdadei Am J Med 92:104–106, 1992

Sporotrichosis (Sporothrix schenckii) JAAD 40:272–274, 1999

Legionella pneumophilia J Infect Chemother 16:439–442, 2010

Staphylococcus aureus Ped 18:249, 1956

Leukocyte adhesion deficiency type 1 – autosomal recessive; pyoderma gangrenosum leg ulcers healing with flaccid scarring; absence of defect of beta2 integrin subunit (CD 18); delayed separation of umbilical stump; recurrent skin and systemic infections; abnormal wound healing Ped Derm 27:500–503, 2010; Nat Rev Immunol 7:678–689, 2007; BJD 139:1064–1067, 1998

Staphylococcus epidermidis AD 120:1099, 1984

Moraxella species – preseptal cellulitis and facial erysipelas Clin Exp Dermatol 19:321–323, 1994

Staphylococcal folliculitis in AIDS JAAD 21:1024, 1026, 1989 Stenotrophomonas maltophilia (formerly Pseudomonas maltophilia) – cellulitis, nodules, ecthyma gangrenosum lesions Eur J Clin Microbiol Infect Dis 28:719–730, 2009l J Eur Acad Dermatol Venereol 21:1298–1300, 2007; Ann Pharmacother 36:63–66, 2002; Can J Infect Dis 7:383–385, 1996 Streptococcus iniae NEJM 337:589–594, 1997

Mucormycosis (Mucor, Absidia, Rhizopus, Saksenaea) – rhinoorbital; rhino-cerebral facial cellulitis

Streptococcus pneumoniae Am J Med 59:293, 1975

Mycobacterium abscessus – cellulitis J Clin Inf Dis 24:1147–1153, 1997

Trichophyton rubrum, invasive Cutis 67:457–462, 2001

Mycobacterium avium intracellulare JAAD 33:528–531, 1995; JAAD 21:574–576, 1989

Streptococcus zooepidemicus Aust NZ J Med 20:177–178, 1990 Trichosporon cutaneum AD 129:1020–1023, 1993 Trypanosomiasis cruzi Int J Dermatol 51:829–834, 2012

Mycobacterium bovis AD 126:123–124, 1990

Vibrio vulnificus Ann Int Med 129:318, 1988

Mycobacterium chelonae – cellulitis J Infect Dis 166:405–412,1992; with pustules JAAD 24:867–870, 1991;

Yersinia enterocolitica

Mycobacterium fortuitum – panniculitis JAAD 39:650–653, 1998; cellulitis Dermatol Surg 26:588–590, 2000

Zygomycosis Ped Inf Dis J 4:672–676, 1985; red plaque with central eschar AD 131:833–834, 836–837, 1995

Xanthomonas maltophilia AD 128:702, 1992

CELLULITIS (PSEUDOCELLULITIS), NON-­INFECTIOUS ETIOLOGIES

CELLULITIS, INFECTIOUS, IN THE IMMUNOCOMPETENT HOST

207

AUTOIMMUNE DISORDERS Allergic contact dermatitis – Rhus; orthopedic implants Dermatomyositis with calcinosis cutis

Semin Cutan Med Surg 26:168–179, 2007

Graft vs host disease

INFECTIONS AND INFESTATIONS

DRUG ERUPTIONS

Aeromonas hydrophilia

Calcium gluconate with calcinosis cutis

Anthrax, cutaneous – cellulitis in intravenous drug abuse Clin Inf Dis 61:1840–1849, 2015

Chlorambucil

Black widow spider bite Brown recluse spider bite Centipede bite Clostridium botulinum, sordelli, novyi – cellulitis in intravenous drug abuse Clin Inf Dis 61:1840–1849, 2015 Contiguous spread of subcutaneous infections Dental sinus or abscess Dermatophytid Dermatophytosis Dirofilaria repens – red plaques (cellulitis-like) and pulmonary nodules BJD 173:788–791, 2015 Dracunculus medinensis (dracunculosis) (Guinea worm) – stagnant water with copepods; painful popular lesions, nausea and vomiting, fever, syncope, urticarial, red papulonodular lesions which become vesiculobullous, cellulitis lesions JAAD 73:929–944, 2015

Clopidogrel bisulfate (systemic inflammatory response syndrome) Coumadin necrosis (early) Fixed drug eruptions, including non-pigmenting fixed drug eruptions Furosemide Gemcitabine Curr Oncol 26:e703–706, 2019; Am J Ther 23:e321– 323, 2016 IL-2 therapy Paracetamol Pemetrexed Clin Exp Dermatol 42:914–916, 2017 L-asparaginase pseudocellulitis Fixed drug eruptions  Topotecan Vitamin K injection reaction Docetaxel extravasation – personal observation Valium, intravenous infiltration – personal observation

Erysipeloid (Erysipelothrix rhusiopathiae) Erythema migrans (Borrelia burgdorferi) Fish stings

EXOGENOUS AGENTS

Hematogenous dissemination from an internal source

Contact dermatitis to underlying mesh/prosthesis

Prevesicular herpes zoster

Irritant contact dermatitis

Insect bite reaction

Milk injections

Leishmaniasis

Paraffinoma

Mucormycosis – ptosis with upper eyelid edema and necrosis JAMA 309:2382–2383, 2013

Silicone reaction/granuloma

Mycobacterium abscessus Mycobacterium chelonae

Vaccinations   Diphtheria-tetanus-acellular pertussis   Wells’ syndrome after DPT vaccine

Mycobacterium kansasii Myiasis (Dermatobia hominis) Necrotizing fasciitis Onchocerciasis (erysipelas de la costa) Parvovirus B19 Phlegmon Pyomyositis Streptococcus pyogenes – intravenous drug abuse Clin Inf Dis 61:1840–1849, 2015; perianal cellulitis JAMA 311:957–958, 2014 Vaccinations – post-vaccination; vaccinia (preseptal cellulitis); Haemophilus influenza B (periorbital and orbital cellulitis) Vibrio vulnificus

CELLULITIS (PSEUDOCELLULITIS), NON-­INFECTIOUS ETIOLOGIES JAAD 67:186–196, 2012; Semin Cutan Med Surg 26:168–179, 2007

INFLAMMATORY DISORDERS Autoinflammatory syndromes  Familial Mediterranean fever – acral erysipelas-like erythema, purpuric lesions, periodic fevers, synovitis, serositis, HenochSchonlein purpura, polyarteritis nodosa, febrile myalgia, amyloidosis JAAD 68:834–853, 2013; giant annular recurrent plaque of buttocks Clin Inf Dis 58:1273–1338, 2014  Tumor necrosis factor receptor-associated periodic syndrome Panniculitis   Erythema nodosum   Subcutaneous fat necrosis of the newborn   Cold panniculitis   Alpha-1 antitrypsin deficiency panniculitis  Lipodermatosclerosis   Lupus panniculitis   Pancreatic panniculitis Neutrophilic diseases   Sweet’s syndrome   Neutrophilic eccrine hidradenitis

208 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Connective tissue diseases   Eosinophilic fasciitis   Eosinophilia myalgia syndrome   Scleroderma (acute edematous phase)   Rheumatoid arthritis with intravascular/lymphatic histiocytosis   Relapsing polychondritis Inflammatory bowel diseases   Metastatic Crohn’s disease Other inflammatory diseases   Wells’ syndrome (eosinophilic cellulitis)   Giant urticarial/angioedema  Autoerythrocyte sensitization syndrome (painful bruising syndrome)  Scleredema   Nephrotic crisis  Erythromelalgia  Erythema overlying infection, inflammation, or tumor (erythema of flank overlying area of bowel perforation)  Sarcoid   Kawasaki’s disease   Compartment syndrome   Breast surgery   Periductal mastitis

         

Genitourinary carcinoma Prostate carcinoma Anaplastic thyroid carcinoma Nasopharyngeal carcinoma Metastatic melanoma

PSYCHOCUTANEOUS DISEASES Factitial dermatitis

SYNDROMES Erythromelalgia

TOXINS Mercury Ricin (with Enterococcus faecalis)

TRAUMA Coma bullae

METABOLIC DISORDERS Calciphylaxis Gout Diabetes mellitus Hematologic diseases   Sickle cell disease   Hereditary spherocytosis

Hematoma Int Wound J 16:297–299, 2019 Occupational high pressure injection injury Pressure bullae; pressure necrosis following back surgery – personal observation Radiation dermatitis Radiation recall reaction

VASCULAR LESIONS NEOPLASTIC DISEASES

Acute inflammatory edema JAAD 81:931–936, 2019

Primary   Inflammatory breast carcinoma  Angiosarcoma   Glucagonoma syndrome   Retinoblastoma (orbital cellulitis)   Multiple myeloma   Epstein-Barr virus-associated lymphoma   Peripheral T-cell lymphoma   NK/T-cell lymphoma   T-cell prolymphocytic leukemia   Primary skeletal muscle hamartoma   Paget’s disease of the breast   Extramammary Paget’s disease   Skeletal muscle lymphoma Cutis 68:223–226, 2001

Acute venous congestion – personal observation

Metastatic carcinoma (carcinoma erysipelatoides)   Ovarian carcinoma   Tonsillar carcinoma   Gastric carcinoma   Uterine carcinoma   Breast carcinoma   Lung carcinoma   Colon carcinoma   Rectal carcinoma   Pancreatic carcinoma   Parotid carcinoma   Squamous cell carcinoma

CEREBRIFORM LESIONS

Generalized essential telangiectasia Leukocytoclastic vasculitis Deep vein thrombosis Phlegmasia cerulea dolens – red swollen leg due to acute extensive venous thrombosis NEJM 378:658, 2018 Popliteal artery occlusion – personal observation Superficial thrombophlebitis Venous insufficiency dermatitis Lymphedema

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSREGULATION Graft vs. host disease, chronic – rippley skin overlying deep sclerodermoid changes JAAD 66:515–532, 2012; AD 138:924–934, 2002 Pemphigus vegetans – cerebriform tongue BJD 104:587–591, 1981; cerebriform lesions over flexures and tongue Indian J Dermatol 6:206–208, 2016 Severe combined immunodeficiency – skin redundancy

Cerebriform Lesions

209

CONGENITAL ANOMALIES

INFLAMMATORY DISORDERS

Abnormal nevoblast migration mimicking neurofibromatosis AD 127:1702–1704, 1991

Dissecting cellulitis of the scalp (perifolliculitis capitis abscessus et suffodiens)- cerebriform scalp nodules JAAD 75:1101–1117, 2016; BJD 174:421–423, 2016; JAAD 53:1–37, 2005

Congenital fascial dystrophy (rippled skin) JAAD 943–950, 1989 Congenital cutaneous plate-like osteoma cutis – mountain range topography Ped Derm 10:371–376, 1993 Double lip Cutis 66:253–254, 2000

DRUG ERUPTIONS Panitumumab (EGFR inhibitor) – cerebriform acneiform eruption; Demodex infestation BJD 174:686–687, 2016

EXOGENOUS AGENTS Aquagenic wrinkling of hands due to rofecoxib Ped Derm 19:353– 355, 2002 Aquagenic wrinkling of hands in cystic fibrosis Ped Derm 25:150– 157, 2008; AD 141:621–624, 2005; Med Biol Immunol 25:205–210, 1975; Lancet 2:953, 1974 Coral dermatitis JAMADerm 155:107, 2019

Hidradenitis suppurativa – personal observation

METABOLIC DISEASES ACTH overproduction in infants – redundant thickened skin Congenital disorders of glycosylation (CDG-Ia) – phosphomannomutase-­2; redundant excess fat; peau d’orange skin; facial dysmorphism, cerebellar hypoplasia, hypotonic neonate, strabismus Ped Derm 22:457–460, 2005 Congenital disorders of glycosylation (CDG-Ix) – nuchal skin folds, facial dysmorphism, inverted nipples, hypoplastic nails, petechiae and ecchymoses, edema; neurologic, gastrointestinal and genitourinary abnormalities, pericardial effusion, ascites, oligohydramnios Ped Derm 22:457–460, 2005 Erythropoietic protoporphyria Hunter’s syndrome – decreased sulfoiduronate sulfatase Ped Derm 15:370–373, 1998 Hyaluronan metabolic abnormality – generalized lax and cerebriform redundant skin J Pediatr 136:62–68, 2000

INFECTIONS AND INFESTATIONS

Obesity – redundant skin

Cellulitis – edema secondary to recurrent bullous cellulitis – personal observation

Tuberous xanthoma

Thyroid acropachy

Chromomycosis Cutis 101:442,447–448, 2018 Giant condyloma of Buschke and Lowenstein – cerebriform, multilobulated giant tumor BJD 166:247–251, 2012 Leprosy AD 148:1096–1097, 2012 Lobomycosis

NEOPLASTIC DISEASES Acrochordon – cerebriform nodule of penis JAAD 59:S35–37, 2008 Apocrine acrosyringeal keratosis arising in syringocystadenoma papilliferum BJD 142:543–547, 2000 Apocrine epithelioma JAAD 13:355–363, 1985

INFILTRATIVE DISEASES

Bowenoid papulosis AD 130:1311–1316, 1994

Amyloidosis – nodular cutaneous amyloidosis AD 133:909–914, 1997; primary systemic amyloidosis – cerebriform plaques of volar fingers AD 148:247–252, 2012; cutis verticis gyrate Indian J Dermatol venereol Leprol 75:394–397, 2009

Clear cell acanthoma (giant) BJD 143:1114–1115, 2000

Juvenile xanthogranuloma Langerhans cell histiocytosis AD 126:1617–1620, 1990 Localized lichen myxedematosus (papular mucinosis) in morbid obesity BJD 148:165–168, 2003 Mastocytoma BJD 144:208–209, 2001; BJD 103:329–34, 1980; diffuse cutaneous mastocytosis – personal observation Pretibial myxedema NEJM 352:918, 2014; Int J Low Extrem Wounds 13:152–154, 2014; Indian J Med Res 137:568, 2013; NEJM 352:918, 2005; AD 127:247–252, 1991 Scleromyxedema (papular mucinosis) – thick folding of skin; cerebriform palmar rippling JAAD 44:273–281, 2001; lichen myxedematosus – cerebriform infiltration of palms and soles Verruciform xanthoma of toes in patient with Milroy’s disease due to persistent leg edema Ped Derm 20:44–47, 2003; JAAD 20:313–317, 1989 Xanthoma disseminatum – mountain range topography AD 121:1313–1317, 1985

Congenital melanocytic nevus JAAD 67:495–511, 2012 Connective tissue nevus (collagenoma) – paving stone nevus Ped Derm 11:84–85, 1994; isolated palmar cerebriform collagenoma AD 133:909–914, 1997; isolated plantar cerebriform collagenoma Ped Derm 11:84–85, 1994; AD 127:1589–1590, 1991; of 5th toe unassociated with Proteus syndrome J Dermatol 42:219–220, 2015; JAAD 58:497–499, 2008 Connective tissue nevi may be seen in:   Buschke-Ollendorff syndrome   Down’s syndrome   Ehlers-Danlos syndrome   Eruptive collagenoma   Familial cutaneous collagenoma   Hunter syndrome (pectoral and scapular)   Knuckle pads   MEN Type I – eruptive collagenomas   Proteus syndrome   Pseudoxanthoma elasticum   Tuberous sclerosis Cylindromas AD 137:219–224, 2001 Dermatofibrosarcoma protuberans Ped Derm 29:707–713, 2012

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Eccrine poroma, giant Cutis 88:227–229, 2011; AMA Arch Derm 74:511–521, 1956 Eccrine syringofibroadenoma AD 126:945–949, 1990; reactive peristomal eccrine syringofibroadenoma – cerebriform verrucous plaque JAAD 58:691–696, 2008

PRIMARY CUTANEOUS DISEASES Aquagenic syringeal acrokeratoderma Dermatology 204:8, 2002; JAAD 45:124, 2001 Cutis laxa – redundant skin

Elastoma in actinically damaged skin JAAD 52:1106–1108, 2005

Cutis verticis gyrata (see separate chapter)

Epidermal nevus – personal observation

Ichthyosis en confetti – neonatal ichthyosiform erythroderma, hyperpigmented verrucous and cerebriform plaques of heels and neck BJD 176:249–251, 2017

Keloid Keratoacanthoma Leiomyomatosis Genetic Skin Disorders, Second Edition, 2010, pp.592–594

Striae, cerebriform

Lipoma

SYNDROMES

Lymphoma – cutaneous T-cell lymphoma AD 138:191–198, 2002; cerebriform lesions of scalp – folliculotropic cutaneous T-cell lymphoma AD 144:738–746, 2008; primary cutaneous large B-cell lymphoma of the legs AD 132:1304–1308, 1996; Ki-1+ lymphoma; adult T-cell leukemia/lymphoma BJD 155:617–620, 2006; ; CD8+ small/medium sized pleomorphic T-cell lymphoma BJD 170:204– 206, 2014

Beare-Stevenson syndrome – cutis verticis gyrata of scalp, cutis gyrata (furrowed skin), corrugated forehead, acanthosis nigricans, macular hyperpigmentation of antecubital and popliteal fossae, hypertelorism, swollen lips, swollen fingers, prominent eyes, ear anomalies, and umbilical herniation Ped Derm 20:358–360, 2003

Melanocytic nevus, congenital (cerebriform intradermal nevus) JAAD 68:441–451, 2013; Ped Derm 26:615–616, 2009; Ped Derm 25:43–46, 2008; Ped Derm 24:141–143, 2007; J Eur Acad DV 16:529–531, 2002; J Pediatr 120:906–911, 1992; Rook p. 1733– 1735, 1998, Sixth Edition; giant cerebriform intradermal nevus Dermatol Surg 28:75–79, 2002; Ann Plast Surg 19:84–88, 1987

Bilateral cerebriform collagenomas and varicose veins; mosaic AKT1 mutation JAMADerm 150:990–993, 2014 Brooke-Spiegler syndrome – giant cerebriform eccrine spiradenoma Int J Surg Case Rep 51:277–281, 2018 Cardio-facio-cutaneous syndrome – skin redundancy

Melanoma JAAD 58:880–884, 2008

Cutis verticis gyrata-mental deficiency syndrome Clin Dysmorphol 7:131–134, 1998

Melanoma arising in a giant cerebriform nevus AD 96:536–539, 1967; nodular amelanotic metastases BJD 142:533–536, 2000

Donahue’s syndrome (leprechaunism) – redundant thickened skin

Mucinous nevus (connective tissue hamartoma) AD 141:897–902, 2005

Ehlers-Danlos syndrome – redundant skin on palms and soles

Nevus lipomatosis superficialis AD 143:1583–1588, 2007; Ped Derm 20:313–314, 2003; Ped Derm 13:345–346, 1996; Arch Dermatol Syphilol 130:327, 1921; pedunculated cerebriform nodule Ped Derm 36:152–153, 2019; nevus lipomatosus superficialis with folliculosebaceous cystic hamartoma – hyperpigmented cerebriform mass JAAD 56:S55–56, 2007 Nevus sebaceus Ped Derm 25:355–358, 2008; papillomatous pedunculated nevus sebaceus BJD 176:204–208, 2017; Rook p.535, 1998, Sixth Edition Sclerotic granular cell tumor – hypertrichotic cerebriform nodule JAMA Derm 149:609–614, 2013 Signet ring cell carcinoma, primary cutaneous JAAD 54:532–536, 2006 Seborrheic keratosis – personal observation Smooth muscle hamartoma Genital squamous cell carcinoma – cerebriform (mulberry-like); multilobulated nodules BJD 171:779–785, 2014 Syringocystadenoma papilliferum – cerebriform multilobulated pink nodules of legs AD 148:1411–1416, 2012 Syringofibrocarcinoma in Clouston’s syndrome – cerebriform plaque of foot JAMADerm 152:484–485, 2016 Trichoblastoma J Dermatol 24:174–178, 1997 Verrucous carcinoma

PARANEOPLASTIC DISORDERS Tripe palms – rippled skin JAAD 54:745–762, 2006; Clinics Derm 11:165–174, 1993

Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa with cerebriform tongue, corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005 Laron dwarfism – redundant thickened skin Maffucci’s syndrome Michelin tire syndrome with smooth muscle hamartoma in males – diffuse smooth muscle hamartoma; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques JAAD 46:477–490, 2002; JAAD 28:364–370, 1992; Ped Derm 6:329–331, 1989; nevus lipomatosis in females JAAD 46:477–490, 2002; congenital diffuse lipomatosis Mucopolysaccharidoses – personal observation Multiple endocrine neoplasia syndrome (MEN I) – angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328– 5336, 2004; AD 133:853–857, 1997 Neurofibromatosis type I – neurofibromas of the feet Rook p.379, 1998, Sixth Edition; Dermatol Clinics 13:105–111, 1995; Curr Prob Cancer 7:1–34, 1982; NEJM 305:1617–1627, 1981 Pachydermoperiostosis – cerebriform facial features JAAD 31:947–953, 1994; Medicine 70:208–214, 1991; AD 124:1831– 1834, 1988; cerebriform rippling of palms and soles J Dermatol 27:106–109, 2000 POEMS syndrome – glomeruloid hemangioma Clin Exp Dermatol 3:775–777, 2006

CHEILITIS (CRUSTED LIPS) Proteus syndrome – cerebroid thickening of palms and soles (cerebriform connective tissue nevi); linear epidermal nevus, asymmetric disproportionate overgrowth; before second decade – ovarian cystadenoma or parotid monomorphic adenoma; lipomas, regional lipo hypoplasia, vascular malformations (capillary, venous, lymphatic), lung cysts, facial phenotype – dolichocehaly, long face, down slanting palpebral fissures and/or mild ptosis, low nasal bridge, wide or anteverted nares, open mouth at rest; dermal hypoplasia, localized hypertrichosis, patchy light scalp hair, phylloid or linear hyperpigmented macules, gingival overgrowth JAAD 78:725–732, 2018; J Drugs in Dermatol 12:586–587, 2013; JAAD 63:799–804, 2010; JAAD 63:1–22, 2010; JAAD 56:353–370, 2007; Am J Med Genet A 143:2944–2958, 2007; JAAD 52:834– 838, 2005; JAMA 285:2240–2243, 2001; AD 133:77–80, 1997; JAAD 25:377–383, 1991; Ped Derm 6:344–345, 1989; AD 125:1109–1114, 1989; Eur J Pediatr 140:5–12, 1983; Birth Defects Orig Artic Ser 15:291–296, 1979; multilobulated cerebriform scalp nodule (connective tissue nevus) JAAD 67:890–897, 2012; must be distinguished from hemihyperplasia-multiple lipomatosis syndrome (CLOVE syndrome) (congenital lipomatous overgrowth, vascular malformation, epidermal nevi) Am J Med Genet 79:311– 318, 1998 Prune belly syndrome (aplastic abdominal musculature syndrome) (Triad syndrome; Eagle-Barrett syndrome, urethral obstruction malformation sequence) – abdominal muscle hypoplasia, urinary tract abnormalities, bilateral cryptorchidism, pulmonary, skeletal, cardiac and gastrointestinal abnormalities; cerebriform appearance of abdomen; loose and wrinkled skin at birth Ped Derm 23:342–345, 2006; J Urol 139:335–337, 1988 Pseudoxanthoma elasticum – redundant skin

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 HALKY MATERIAL EXTRUDED C FROM LESIONS Calcinosis cutis- idiopathic calcinosis cutis Rook p. 2664, 1998, Sixth Edition; dystrophic calcification in chronic renal failure, scleroderma, CREST syndrome Rook p. 2529, 1998, Sixth Edition; tumoral calcinosis – around hip, elbow, ankle, and scapula Seminars in Dermatol 3:53–61, 1984; J Dermatol 23:545–550, 1996; exogenous calcium AD 89:360–363, 1964; EEG/EMG paste – firm yellow plaque with or without extrusion of white material; red nodule with white extrusion Cutis 52:161–164, 1993; calcinosis cutis secondary to subcutaneous calcium heparin injections JAAD 50:210–214, 2004; metastatic calcification Calcium oxalate Epidermoid cyst Gouty tophi Cutis 48:445–451, 1991; Ann Rheum Dis 29:461–468, 1970 Idiopathic calcinosis of the scrotum JAAD 19:1095–1010, 1988; Eur Urol 13:130–131, 1987 Multicentric reticulohistiocytosis Myeloma with cryoglobulinemia – follicular spicules JAAD 32:834– 839, 1995 Osteoma cutis Am J Dermatopathol 15:77–81, 1993 Pilomatrixoma Rheumatoid nodules Xanthomas

Rubinstein-Taybi syndrome SCALP syndrome (didymosis aplasticosebacea) – cerebriform nevus sebaceus; aplasia cutis congenita, pigmented nevi, CNS malformation, limbal dermoid Ped Derm 29:15–23, 2012 Shulman’s syndrome (eosinophilic fasciitis) – rippled skin Turner’s syndrome – lymphedema of the scalp mimicking cutis verticis gyrata Ped Derm 15:18–22, 1998

CHEILITIS (CRUSTED LIPS)  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – multiple allergens

Hemangioma

Dermatitis 21:111–115, 118–120,121–122, 2010; amine fluoride in toothpaste Dermatitis 25:209, 2014; lipsticks, lip salves, mouthwashes, dentifrices, dental preparations, foods, citrus fruits, mango, nail polish, sunscreen Contact Dermatitis 45:173, 2001; AD 134:511–513, 1998; JAAD 39:488–490, 1998; Contact Dermatitis 33:365–370, 1995; cigarettes Dermatitis 20:6–13, 2009; angular cheilitis; granulomatous cheilitis – cobalt Clin Exp Dermatol 15:384–396, 1990; cinnamic aldehyde (food additive) BJD 131:921–922, 1994; toothpaste – multiple allergens Contact Dermatitis 20:95–98, 2009; sodium laurel sulfate in toothpaste Contact Dermatitis 42:111, 2000; potassium persulfate in dental cleanser Contact Dermatitis 41:268–271, 1999; colophonium in dental floss Am J Contact Dermatitis 10:198–200, 1999; castor oil in lipstick Contact Dermatitis 42:114–115, 2000; allergic contact dermatitis to benzoates in cola drinks Ped Derm 33:213–215, 2016

Hemangiopericytoma – solitary violaceous congenital lesion of plantar aspect Ped Derm 23:84–86, 2006

Anti-laminin 332 mucous membrane pemphigoid – after diphtheria/ tetanus vaccination JAMA Derm 149:858–862, 2013

Lymphangioma Lymphedema, congenital (Milroy’s disease)

Chronic granulomatous disease – cheilitis JAAD 36:899–907, 1997; JAAD 23:444–450, 1990

Lymphedema precox

Cicatricial pemphigoid

Lymphostasis verrucosa cutis (chronic lymphedema) (KaposiStemmer sign) – failure to pick up fold of skin

DOCK 8 deficiency – herpes simplex erosive stomatitis and cheilitis JAAD 73:355–364, 2015

TRAUMA Frictional perianal decubitus ulcer – personal observation Immersion foot (rippled skin)

VASCULAR LESIONS Congenital plaque type glomuvenous malformations – glomulin gene on 1p21; loss of function mutation; atrophic at birth; livedoid plaques, blue plaques, vascular nodules, red patches, cerebriform, targetoid AD 142:892–896, 2006 Giant angiofibroma Cutis 42:429–432, 1988

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Familial pyoderma gangrenosum with common variable immunodeficiency – vegetative cheilitis; cutaneous ulcers BJD 169:944–946, 2013 Lupus erythematosus – systemic lupus erythematosus BJD 144:1219–1223, 2001; BJD 135:355–362, 1996; BJD 121:727–741, 1989; cheilitis with erosions in SLE AD 148:113–118, 2012; discoid LE – lip ulcer, systemic lupus erythematosus, subacute cutaneous lupus erythematosus BJD 135:355–362, 1996; Clin Exp Dermatol 11:309–313, 1986; bullous lupus erythematosus Pemphigus vegetans, Neumann variant JAAD 39:872–875, 1998 Pemphigus vulgaris BJD 161:313–319, 2009; in pregnancy Cutis 94:206–209, 2014; IgA/IgG pemphigus Ped Derm 22:321–327, 2005

disease carbamazepine, phenobarbital, hydantoins, INH, azathioprine, chloramphenicol, ethionamide, protionamide; aphthous ulcers and JAAD 67:1113–1127, 2012; JAAD 46:597–599, 2002; Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; BJD 125:71–72, 1991 Penicillamine Arch Int Med 120:374–376, 1967 Pravastatin – cheilitis Cutis 62:197–198, 1998 Protease inhibitors AIDS 14:1289–1291, 2000 Quinidine photo-induced lichen planus – personal observation Radiation recall – capecitabine, doxorubicin, taxanes, gemcitabine; erythema and desquamation; edema; vesicles and papules; ulceration and skin necrosis The Oncologist 15:1227–1237, 2010 Simvastatin Cutis 62:197–198, 1998

Sjogren’s syndrome – red swollen lip J Dermatol 28:47–49, 2001; angular cheilitis

6-mercaptopurine and mesalamine – erythrodysesthesia; swollen red lips; red and eroded palms and soles AD 144:1079–1080, 2008

DEGENERATIVE DISEASES

Sorafenib (multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of feet, hyperkeratotic plaque or blister of feet, red patches on pressure points, red swollen fingertips, gray blisters of finger webs, angular cheilitis, perianal dermatitis BJD 158:592–596, 2008

Angular cheilitis – due to recession of bony support of lower mouth SkinMed 11:198–200, 2013

DRUG-INDUCED Anticholinergics Anticonvulsants Antihistamines Antineoplastics Capecitabine (Xeloda) Indian Dermatol Online J 5:349–352, 2014; JAAD 45:790–791, 2001 Crizotinib-induced lichenoid eruption Cutis 102:403–406, 2018 Diuretics DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome – cheilitis, facial edema, exanthema, erythroderma, oral erosions BJD 169:1071–1080, 2013

Toxic epidermal necrolysis BJD 68:355–361, 1956 Trametinib (MAP kinase inhibitor) (MEK inhibitor) – angular cheilitis, xerosis, bacterial folliculitis, acneiform eruptions, paronychia, thinning hair Ped Derm 34:90–94, 2017 Voriconazole – photodermatitis and photo-cheilitis with acute and chronic changes of sun damage JAAD 62:31–37, 2010; JAAD 52:S81–85, 2005; photodermatitis and retinoid-like dermatitis Ped Derm 21:675–678, 2004; Pediatr Infect Dis J 21:240–248, 2002; Clin Exp Dermatol 26:648–653, 2001

EXOGENOUS AGENTS Betel chewer’s perleche BJD 89:98, 1973 Chlorhexidine

Drug eruptions, multiple types

Cocaine – cracked lips; crack cocaine cheilitis JAAD 69:135–142, 2013

5-fluorouracil, topical treatment of actinic cheilitis – personal observation

Irritant contact dermatitis – many agents; capsicum (red peppers) red hands and red lips Cutis 72:21–23, 2003

Fixed drug eruptions JAMA 312:2281–2282, 2014; Int J Derm 37:833–838, 1998

Silica granuloma – mimics granulomatous cheilitis Dermatologica 181:246–247, 1990

HAART (high activity antiretroviral therapy) therapy – eruptive cheilitis Med Oral 6:19–30, 2001

Tattooing, cosmetic AD 141:918–919, 2005

Hepatitis B vaccine – necrolytic acral erythema; psoriasiform dermatitis, acral erythema and scale, cheilitis, verrucous papules of eyelids and around nose BJD 171:1255–1256, 2014 Imiquimod – hemorrhagic cheilitis Cutis 89:276–277, 2012

Vitamin A toxicity J Hepatol 31:142–148, 1999; Ann DV 118:51–52, 1991

INFECTIONS AND/OR INFESTATIONS

Indinavir (cheilitis) – lip fissures and cheilitis JAAD 63:549–561, 2010; JAAD 46:284–293, 2002; Sex Transm Infect 76:323–324, 2000

Abscess, Staphylococcus aureus – personal observation

Isotretinoin (retinoid cheilitis) Clin Pharm 8:344–351, 1989; Dermatologica 175 Suppl 1:151–157, 1987

Bejel

Itraconazole – photodermatitis and retinoid-like dermatitis J Eur Acad Dermatol Venereol 14:501–503, 2000

Cancrum oris (noma)

Lovastatin – cheilitis Cutis 62:197–198, 1998 Mevastatin – cheilitis Cutis 62:197–198, 1998 Narcotics Postgrad Med J 68:303–304, 1992

AIDS – photo-lichenoid eruption of AIDS Botryomycosis Cutis 55:149–152, 1995 Candida cheilitis (angular cheilitis) (perleche) Med Oral 2:201–208, 1997; J Oral Pathol 15:213–217, 1985; chronic mucocutaneous candidiasis; candidiasis in AIDS

Praliatrexate – personal observation

Elephantiasis nostras of the lips – presumed streptococcal infection Oral Surg Oral Med Oral Pathol Endod 84:297–300, 1997

Pellagrous dermatitis – drug-induced pellagra-like dermatitis – 6-­mercaptopurine, 5-fluorouracil,INH (all of the above – also seborrheic dermatitis-like); fissured cheilitis; resembles Hartnup

Chronic active Epstein-Barr virus – vulvitis, hemorrhagic cheilitis, necrotic ulcers, periorbital erythema and edema, maxillary sinusitis, hepatosplenomegaly BJD 173:1266–1270, 2015

Cheilitis (Crusted Lips) Fuchs syndrome – Stevens-Johnson syndrome without skin lesions AD 148:963–964, 2012 Hand foot and mouth disease (Coxsackie virus) Rook p. 3133–3134, 1998, Sixth Edition Herpes simplex – primary, recurrent, eczema herpeticum Herpes zoster Impetigo – streptococcal or staphylococcal Leishmania brasiliensis J Clin Inf Dis 22:1–13, 1996

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2016; An Bras Dermatol 86:S137–140, 2011; Med Oral Patol Oral Cir Bucal 14:E114–117, 2009; Ann DV 135:753–756, 2008; Dermatology 217:146–148, 2008; Clin Exp Dermatol 29:1–7, 2004 Sarcoid – granulomatous cheilitis JAAD 29:822–824, 1993; split papules Dermatol Clin 33:509–630, 2015 Stevens-Johnson syndrome/toxic epidermal necrolysis – erosive cheilitis BJD 174:1194–1227, 2016 Toxic epidermal necrolysis BJD 68:355–361, 1956

Measles – red granular lips Mycobacterium tuberculosis – orofacial granulomatosis due to tuberculosis; enlarged tongue; vegetative plaques of nose and nasolabial folds Ped Derm 26:108–109, 2009 Orf Br Dent J 173:343–344, 1992 Paracoccidioidomycosis (Paracoccidioides brasiliensis) JAAD 53:931–951, 2005 Parvovirus B 19, including papular-purpuric "gloves and socks" syndrome – swollen lips with painful erosive cheilitis JAAD 41:793–796, 1999 Scarlet fever Scopulariopsis brevicaulis – ulcerous granulomatous cheilitis JAAD 31:881, 1994

METABOLIC Acrodermatitis enteropathica (zinc deficiency) – periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche Cutis 81:314, 324–326, 2008; JAAD 56:116–124, 2008; Ped Derm 19:426–431, 2002; angular cheilitis Cutis 82:60–62, 2008; Ped Derm 19:426–431, 2002; Acta DV 17:513–546, 1936; acquired zinc deficiency with erythema and scaling of entire vermilion in cystic fibrosis – personal observation; acquired zinc deficiency from parenteral nutrition – acral erosions and bullae, cheilitis Ped Derm 36:520–523, 2019 Celiac disease – angular cheilitis

Staphylococcus aureus – angular cheilitis fissuring of midline of lower lip Clin Exp Dermatol 11:289–291, 1986

Folic acid deficiency – angular cheilitis Lancet Aug 28;2(7722):453– 454, 1971

Syphilis – primary chancre; secondary – split papules (angular cheilitis) congenital syphilis – split papules

Hartnup’s disease – cheilitis and angular stomatitis

Trichophyton rubrum Oral Surg Oral Med Oral Pathol 30:201–206, 1970 Vaccinia Br Dent J 143:57–59, 1977 Varicella Yaws

INFILTRATIVE Plasma cell cheilitis – with lip ulcer JAAD 30:789–780, 1994

INFLAMMATORY DISEASES Cheilitis granulomatosa (Miescher’s cheilitis) Oral Dis 3:188–192, 1997; AD 124:1706- 1709, 1988; J Oral Maxillofac Surg 44:474– 478, 1986; Dermatologica 91:57–64, 1945 Crohn’s disease – granulomatous cheilitis, fissures of lips, and angular cheilitis with ulceration; multiple aphthae, cobblestoning of the buccal mucosa, linear ulcers of the sulci, pyostomatitis vegetans, fissures of the lower lip, tiny nodules of the gingival and alveolar mucosa J Pediatr Gastroenterol Nutr 32:339–341,2001; AD 135:439–442, 1999; JAAD 36:986–988, 1997; J R Soc Med 75:414–417, 1982; JAAD 5:689–695, 1981; angular cheilitis Erythema multiforme – hemorrhagic cheilitis with erosions of Stevens-­Johnson syndrome BJD 174:1194–1227, 2016 Granulomatous cheilitis – personal observation Orofacial granulomatosis Br Dent J 163:154–157, 1987 Periadenitis mucosae necrotica recurrens (Sutton’s disease) AD 133:1161–1166, 1997 Pyostomatitis vegetans – swollen, pustular lips and nose; erosive plaques of lips with yellow crusts; association with ulcerative colitis and Crohn’s disease JAMADerm 156:335, 2020; JAAD 75:578–584,

Iron deficiency – angular cheilitis J Am Dent Assoc 99:640–641, 1979 Kwashiorkor (protein and caloric deprivation) – angular cheilitis and cheilitis Cutis 67:321–327, 2001; JAAD 21:1–30, 1989 Liver disease, chronic (cirrhosis) – cheilitis; zinc deficiency; generalized dermatitis of erythema craquele (crackled and reticulated dermatitis) with perianal and perigenital erosions and crusts, hair loss Ann DV 114:39–53, 1987 Malabsorption – angular cheilitis Methylmalonic acidemia, cobalamin C type – red lips Dermatol Pediatr Lat 1:46–48, 2003; AD 133:1563–1566, 1997 Pellagra (niacin deficiency) – angular stomatitis; crusted lips; Casal’s necklace; red pigmented sharply marginated photodistributed rash, including drug-induced pellagra-like dermatitis – 6-mercaptopurine, 5-fluorouracil,INH (all of the above – also seb derm-like); resembles Hartnup disease BJD 164:1188–1200, 2011; Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; BJD 125:71–72, 1991 Pernicious anemia – angular cheilitis Porphyria cutanea tarda – cheilitis of lower lip Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:705–708, 2000; angular cheilitis Pseudoglucagonoma syndrome due to malnutrition – angular cheilitis AD 141:914–916, 2005 Uremic stomatitis – personal observation Vitamin B2 (riboflavin) deficiency – angular cheilitis; sore red lips, tongue, and mouth Ped Derm 35:796–799, 2018; Clinics in Derm 17:457–461, 1999; AD 112:70–72, 1976 Zinc deficiency, acquired – perleche (angular cheilitis) JAMA Derm 149:357–362, 2013; cheilitis JAAD 69:616–624, 2013

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NEOPLASTIC DISEASES

PRIMARY CUTANEOUS DISEASE

Actinic cheilitis – hyperkeratotic, scaling, erosive cheilitis JAAD 66:173–184, 2012; Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:181–186, 1999; Derm Surg 23:15–21, 1997

Angular cheilitis – candida, staphylococci, immune deficiency, dentures, overbite, atopic dermatitis, riboflavin, iron, folate deficiencies, protein malnutrition, hypersalivation (drooling) (Down’s syndrome), edentulous patients, prognathism

Basal cell carcinoma Benign lymphoplasia – pruritic cheilitis; itching of the vermilion border Oral Surg Oral Med Oral Pathol 55:759–767, 1983; Oral Surg Oral Med Oral Pathol 55:359–362, 1983

Atopic cheilitis Am J Contact Dermatitis 10:198–200, 1999; Allergy 46:125–128, 1991; Dermatologica 177:360–364, 1988

Hydroa vacciniforme-like cutaneous T-cell lymphoma (Epstein-Barr virus associated lymphoproliferative disorder), Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, pitted scars, fever JAAD 81::534–540, 2019; JAAD 69:112–119, 2013; BJD 151:372–380, 2004

Cheilitis glandularis (Puente’s disease) – inflammatory condition of the lower lip minor salivary glands; enlargement with a mucus ductal discharge, eversion, erythema, and hardening of the lip JAAD 62:233–238, 2010; AD 142:1643–1648, 2006; JAAD 54:338–340, 2006; Oral Surg Oral Med Oral Pathol 78:319–322, 1994; Oral Surg Oral Med Oral Pathol 62:654–656, 1986; Arch Pathol Anat 50:142–144, 1850

Hyperkeratotic cheilitis in association with proliferative verrucous leukoplakia JAAD 41:481–483, 1999 Leukoplakia Leukemic macrocheilitis JAAD 14:353–358, 1986 Squamous cell carcinoma

Cheilitis exfoliativa (chapped lips) Dermatology 196:253–255, 1998

Chronic fissure cheilitis – due to anterior dental crowding Am J Orthod Dentofacial Orthop 119:71–75, 2001 Focal acantholytic dyskeratosis – crusted patch of lip Am J Dermatopathol 17:189–191, 1995 Ichthyosiform dermatosis with superficial blister formation and peeling JAAD 34:379–385, 1996 Kimura’s disease – hemorrhagic cheilitis JAAD 43:905–907, 2000

PARANEOPLASTIC DISEASES Glucagonoma syndrome (necrolytic migratory erythema) – angular cheilitis; scaling papules and plaques, acral bullae, atrophic glossitis AD 143:1221–1222, 2007; JAAD 24:473–477, 1991 Glucagon cell adenomatosis – necrolytic migratory erythema; cheilitis and painful glossitis JAAD 65:458–459, 2011 Malignant acanthosis nigricans – verrucous papules at corners of mouth Cutis 89:14–16, 2012 Paraneoplastic pemphigus (paraneoplastic autoimmune multiorgan syndrome) – erosive cheilitis; oral crusts and erosions, acral bullae BJD 174:930–932, 2016; BJD 172:831–834, 2015; JAMADerm 151:439–440, 2015; JAMA Derm 149:1116–1117, 2013; Ped Derm 29:656–657, 2012; BJD 160:468–470, 2009; JAAD 54:745–762, 2006; crusted lips BJD 169:469–472, 2013; associated with Castleman’s disease, non-Hodgkin’s lymphoma, thymoma, or follicular dendritic cell sarcoma BJD 153:558–564, 2005; Hautarzt 52:159–172, 2001; NEJM 323:1729–1735, 1990

PHOTODERMATITIS Acute sunburn Actinic prurigo – cheilitis, conjunctivitis, eyebrow alopecia, dermatitis, facial scars SKINmed 13:287–295, 2015; The Dermatologist May, 2015, pp 47–48, 50, 2015; JAAD 67:1093– 1110, 2012; Dermatol Ther 16:40–44, 2003; BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981; with generalized pruritus JAMADerm 156:697– 698, 2020 Hydroa vacciniforme – blistering of lips JAAD 67:1093–1110, 2012; necrotic lip lesions with edema AD 142:651, 2006; AD 122:1310–1313, 1986; hydroa vacciniforme (Epstein-Barr virus-related) – red macules progress to tender papules or vesiculo papules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of cheeks, eyelids, ears, and lips AD 142:587–595, 2006 Phytophotodermatitis

Lichen planus BJD 138:145–146, 1996; BJD 132:1000–1002, 1995; bullous lichen planus – personal observation Median deep vertical fissure of lower lip Xerosis

PSYCHOCUTANEOUS DISEASE Factitial cheilitis (cheilitis exfoliativa, cheilorrhagia and cheilitis glandularis) Ped Derm 16:12–15, 1999; Dermatologica 170:93–97, 1985; JAAD 8:368–372, 1983; AD 117:338–340, 1981

SYNDROMES Acantholytic ectodermal dysplasia (similar to McGrath syndrome) – curly hair, palmoplantar keratoderma, skin fragility, hyperkeratotic fissured plaques with perioral involvement, red fissured lips, nail dystrophy BJD 160:868–874, 2009 Bloom’s syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; blisters of nose and cheeks; slender face, prominent nose; facial telangiectatic erythema and hyperpigmentation with involvement of eyelids, ear, hand and forearms; bulbar conjunctival telangiectasias; cheilitis of upper and lower lips; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy; no neurologic deficits; DNA repair defect with chromosomal breaks, sister chromatid exchanges, and triradial and quadriradial chromosomes; mutation in recQ DNA helicase JAAD 75:855–870, 2016; Ped Derm 27:174–177, 2010; Ped Derm 22:147–150, 2005; Curr Prob Derm 14:41–70, 2002; Ped Derm 14:120–124, 1997; JAAD 17:479–488, 1987; AD 114:755–760, 1978; Clin Genet 12:85–96, 1977; Am J Hum Genet 21:196–227, 1969; Am J Dis Child 116:409–413, 1968; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema

Cheilitis (Crusted Lips) with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks and arms, chondritis with progressive ear and saddle nose deformities, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, splenomegaly, protuberant abdomen JAAD 62:489–495, 2010 Darier’s disease Dowling-Meara syndrome (epidermolysis bullosa simplex) – crusted angular cheilitis Genetic Skin Disorders, Second Edition, 2010, pp.145–149 Down’s syndrome – cheilitis with fissured lip Ped Derm 24:317–320, 2007 Ectodermal dysplasia-skin fragility syndrome – autosomal recessive; plakophilin gene mutation (PKP1) – perioral fissuring and cheilitis; perianal erythema and erosions, follicular hyperkeratosis; widespread skin fragility, alopecia of scalp and eyebrows, focal palmoplantar keratoderma with painful fissures, hypohidrosis; skin peeling; generalized erythema and peeling at birth; JAAD 55:157– 161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004 Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC syndrome) – perioral and labial vegetative papillomatous plaques; perleche; high forehead, maxillary hypoplasia, mandibular protrusion Ped Derm 27:658–660, 2010; J Eur Acad DV 17:356–358, 2003; Ped Derm 19:330–332, 2002 Hermansky-Pudlak syndrome – granulomatous cheilitis Society of Pediatric Dermatology Annual Meeting, July, 2015 Hereditary mucoepithelial dystrophy – autosomal dominant; angular cheilitis; red eyes, non-scarring alopecia, keratosis pilaris, erythema of oral (palate, gingiva) and nasal mucous membranes, cervix, vagina, and urethra; photophobia, keratosis pilaris, non-scarring alopecia, psoriasiform perineal plaques, angular cheilitis, nail deformity, increased risk of infections, fibrocystic lung disease BJD 153:310–318, 2005; Ped Derm 12:195, 1995; JAAD 21:351–357, 1989; Am J Hum Genet 31:414–427, 1979; Oral Surg Oral Med Oral Pathol 46:645–657, 1978 Hemophagocytic syndrome – parvovirus B19-induced hemophagocytic syndrome in systemic lupus erythematosus; violaceous plaques and erythema of scalp, face, and back with erosions and erosive cheilitis JAAD 57:S111–114, 2007 Hughes syndrome – acromegaloid features and thickened oral mucosa; thickened fissured lips J Med Genet 22:119–125, 1985 Hyper IgE syndrome Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked recessive; linear plantar hyperkeratosis of heels; linear hairless scalp area in female carriers; ichthyosis, atopic dermatitis, alopecia, follicular papules, nail dystrophy, hyperextensible joints, photophobia, cheilitis, growth and psychomotor retardation, recurrent respiratory and skin infections, cryptorchidism, muscular hypotonia, skeletal abnormalities, inguinal hernia, congenital aganglionic megacolon, corneal vascularization and blindness; mutation in MBTPS2 (membrane bound transcription factor protease, site 2) (zinc metalloprotease) JAAD 64:716–722, 2011; Am J Med Genet 85:365–368, 1999; Ped Derm 26:427–431, 2009; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; Ped Derm 12:195, 1995; AD 125:103–106, 1989; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999; BJD 21:165–189, 1909 IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash;

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mutations in FOXP3 gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia BJD 160:645–651, 2009; ichthyosiform eruptions Blood 109:383–385, 2007; NEJM 344:1758–1762, 2001; alopecia areata AD 140:466–472, 2004 Kawasaki’s disease – cheilitis, meningitis, and unilateral cervical adenopathy in children Ped Derm 36:274–282, 2019; JAAD 69:501–510, 2013; erythematous and/or fissured lips JAAD 39:383–398, 1998 Keratosis-ichthyosis-deafness (KID) syndrome – reticulated severe diffuse hyperkeratosis of palms and soles, well marginated, serpiginous erythematous verrucous plaques, perioral furrows, leukoplakia, sensory deafness, photophobia with vascularizing keratitis, blindness Ped Derm 29:349–357, 2012; Ped Derm 23:81–83,2006; JAAD 23:385–388, 1990; AD 123:777–782, 1987; AD 117:285–289, 1981; bright red thickened lips; fissured lips; perleche; hyperkeratotic papules and plaques of face, scalp, trunk, extremities; exaggerated diaper dermatitis Clinics in Dermatol 23:23–32, 2005; Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990 KID syndrome with fissured lips – paronychial pustules, blepharitis without keratitis, perineal psoriasiform plaques, tongue erosions, honeycomb palmoplantar keratoderma; red gingivae; mutation in connexin 26 (N14K)GJB2 Kindler’s syndrome – angular cheilitis, desquamative lesions of the gingivae; severe periodontal disease; gingivitis; cigarette paper wrinkling of dorsal hands and feet, webbing of fingers, ectropion BJD 160:1119–1122, 2009; BJD 160:233–242, 2009; BJD 159:1192–1196, 2008; BJD 158:1375–1377, 2008; Ped Derm 23:586–588, 2006; AD 142:620–624, 2006; AD 140:939–944, 2004; Oral Surg BJD 158:1375–1377, 2008 Laryngo-onycho-cutaneous syndrome – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3 (LAMA3A) BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedical 2:15–25, 1986 Lesch-Nyhan syndrome – cheilitis due to biting Ped Derm 13:169– 170, 1996 Mal de Meleda – hyperkeratotic angular cheilitis Genetic Skin Disorders, Second Edition, 2010, pp.81–83 Melkersson-Rosenthal syndrome AD 136:1557–1558, 2000; JAAD 21:1263–1270, 1989 Mucoepithelial dysplasia (gap junction disease) – perleche, squinting eyes with photophobia due to keratitis Genetic Skin Disorders, Second Edition, 2010, pp.698–700 Multiple mucosal neuroma syndrome (MEN 2B) – enlarged lips, papules of tongue, Marfanoid habitus; medullary carcinoma of the thyroid; pheochromocytoma; missense gain of function mutation in RET proto-oncogene JAMADerm 152:939–940, 2016 Olmsted syndrome – angular cheilitis with hyperkeratotic plaques Ped Derm 25:223–229, 2008 Pachyonychia congenita type II – natal teeth, bushy eyebrows, follicular keratoses, angular cheilitis, unruly hair BJD 159:500–501, 2008 Peeling skin syndrome, fissured cheilitis, blistering of palms and soles, and desmosomal abnormalities JAAD 34:379–385, 1996 Progressive symmetric erythrokeratoderma

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Reactive arthritis syndrome Shedding oral mucosa syndrome – may be HIV-associated

Acral erythema of proximal nail fold and onychodermal band due to cyclophosphamide and vincristine Cutis 52:43–44, 1993

Shwachman syndrome Ped Derm 9:57–61, 1992

Actinomycin D extravasation

Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – cheilitis, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation JAAD 44:891–920, 2001; Ped Derm 14:441– 445, 1997

Actinic keratoses lighting up – carboplatin, docetaxel Cases J 9:6946–6948, 2009; dactinomycin-dacarbazine-vincristine JAAD 17:192–197, 1987; fludarabine JAAD 17:192–197, 1987; 5-fluorouracil JAAD 53:529–530, 2005; JAAD 43:54—546, 2000; JAAD 39:839–842, 1998; cytarabine, vincristine, doxorubicin Am J Clin Derm 7:45–63, 2006; capecitabine – personal observation

Xeroderma pigmentosum

AGEP (acute generalized exanthematous pustulosis) – imatinib Dermatology 203:57–59, 2001; docetaxel, paclitaxel Eur J Dermatol 26:427–443, 2016

TOXINS

Alopecia – diffuse non-scarring; topoisomerase inhibitors, taxanes, vinca alkaloids, alkylating agents, antimetabolites

Acrodynia – mercury poisoning Ped Derm 21:254–259, 2004

Antibody drug conjugate therapies – diffuse telangiectatic rash JAMADerm 156:601–602, 2020

TRAUMATIC Biting Burns – heat, irradiation, chemicals, electricity Clarinetist’s cheilitis Cutis 38:183–184, 1986 Cold and wind Dental flossing – angular cheilitis JAAD 15:113–114, 1986 Electrical burn Lip licking Am J Contact Dermatitis 10:198–200, 1999 Mechanical trauma Radiation Teething ring cheilitis Cutis 34:362,364, 1984

VASCULAR DISEASES Arteriovenous malformation Pyogenic granuloma

CHEMOTHERAPY, CUTANEOUS MANIFESTATIONS Acneiform eruption – papulopustular rash; epidermal growth factor inhibitors (small molecule tyrosinase kinase inhibitors – erlotinib, gefitinib, lapatinib, afatinib, and monoclonal antibodies – cetuximab, panitumumab, matuzumab) Derm Res Pract 2014:734249; JAAD 58:545–570, 2008; neratinib J Dermatol Treat 30:487–488, 2019; trastazumab – HER2 inhibitor Clin Breast Ca 15:e77–81, 2015 Acral dysesthesia syndrome (palmoplantar erythrodysesthesia syndrome; hand-foot syndrome) – cytosine arabinoside, doxorubicin, and polyethylene glycol-coated liposomal doxorubicin AD 136:1475–1480, 2000; capecitabine, fluorouracil, vinblastine Am J Clin Dermatol 1:225–234, 2000; JAAD 24:457–461, 1991; Cutis 46:397–404, 1990; AD 122:1023–1027, 1986; Ann Int Med 101:12, 1984; sunitinib AD 144:123–124, 2008; cabozantinib JAMADerm 151:170–177, 2015; dabrafenib – painful hyperkeratotic plaques over pressure points JAMADerm 151:102–103, 2015; docetaxel, dorsal hands and feet Ther Adv Drugs Saf 9:495–499, 2109; accentuation along Wallace’s line; psoriasiform plaque; sorafenib JAAD 64:AB113, 2011; floxuridine, idarubicin, vemurafinib, axitinib, cabozanitinib, pazopanib

Azathioprine hypersensitivity syndrome JAAD 65:184–191, 2011 Bullous pemphigoid – immune checkpoint inhibitors, CTLA4, PD-1, PD-L1 JAAD April 2020; radiation JAAD 81:AB261, 2019; nivolumab Oncologist 23:1119–1126, 2018; radiation-induced Radiation and Onc 82:5–9, 2007; pembrolizumab Case Rep Dermatol 10:154–157, 2018 Cytokine release storm – fever, morbilliform rash, transaminitis, no eosinophilia; onset is 10 days after initiation of drug; tolerance after re-introduction, BRAF/MEK inhibitors after prior immunotherapy Melanoma Research 29:107–108, 2019; Melanoma Research 28:451–457, 2018 Dermatomyositis-like rash – bleomycin JAAD 48:439–441, 2003; capecitabine JAMADerm 156:103–104, 2020; hydroxyurea AD 146:305–310, 2010; AD 135:818–820, 1999; ipilimumab JAMADerm 151:195–199, 2015; heliotrope – imatinib J Postgrad Med 58:331– 334, 2012 Dactinomycin – flexural cutaneous necrosis with post-inflammatory hyperpigmentation; morbilliform, macular desquamative dermatitis, brawny erythema AD 142:1660–1661, 2006; dactinomycindacarbazine-­vincristine sulfate – lighting up of actinic keratoses JAAD 17:192–197, 1987 Eccrine squamous syringometaplasia – cytarabine, mitoxantrone, fluorouracil, cisplatin, doxorubicin, cyclophosphamide, etoposide, methotrexate, busulfan, melphalan, carmustine, thiotepa AD 133:873–878, 1977; hydroxyurea JAAD 136:178–182, 1997; imatinib JAAD 55:S58–59, 2006; capecitabine Indian J Dermatol 64:122–128, 2019 Edema, periorbital and facial – sunitinib BJD 161:1045–1051, 2009; JAAD 58:545–570, 2008 Eosinophilia – docetaxel Cancer Med 8:2005–2012, 2019 Eruptive keratoacanthomas – vemurafenib AD 148:363–366, 2012; squamous cell carcinomas with BRAF inhibitors Erythema multiforme – sorafenib Jap J Clin Oncol 42:820–824, 2012; dasatinib JCAD 10:25, 2017 Erythema nodosum – all-trans retinoic acid JAAD 56:690–693, 2007; vemurafenib Gan To Kogaku Ryoho 43:649–653, 2016; J Eur Acad DV 29:1797–1806, 2015; nivolumab, ipilimumab J Cutan Pathol 44:1080–1086, 2017 Etoposide and cyclophosphamide – ultraviolet recall Clin Exp Dermatol 18:452–453, 1993; etoposide, methotrexate, and total body irradiation – ultraviolet recall manifested as edema, erythema, bullae, hemorrhagic crusting, macules, papules, ulceration, necrosis JAAD 56:494–499, 2007 Exfoliative erythroderma/dermatitis – bevacizumab J Drugs Dermatol 1:1052–1055, 2013; vinca alkaloids; mitomycin Int J

Chemotherapy, Cutaneous Manifestations Dermatol 24:472, 1985; cytarabine J Assoc Mil Derm 14:28–29, 1988 Fingertip necrosis – bleomycin, vincristine, and methotrexate BJD 134:378–379, 1996

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Hyperpigmentation, photo-distributed – 5-fluorouracil Hyperpigmentation, reticulated – bleomycin Dermatologica 180:255–257, 1990; 5-fluorouracil Int J Dermatol 34:219–220, 1995 Hypersensitivity syndrome – azathioprine JAAD 65:184–191, 2011

Fingertip loss – capecitabine JAMADerm 156:103–104, 2020

Hypertrichosis EGFR-inhibitors JAAD 55:657–670, 2006

Fingertips red, swollen, tender – sorafenib AD 144:886–892, 2008; BJD 158:592–596, 2008

Hypopigmentation, generalized – bleomycin AD 107:553–555, 1973; busulfan JAAD 9:645–663, 1983; thiotepa JAAD 58:575–578, 2008; imatinib Cancer 98:2483–2487, 2003; imatinib hypopigmentation of distal fingers J Natl Med Assoc 95:722–724, 2003; sunitinib – facial depigmentation JAAD 61:905–906, 2009

Flagellate erythema/hyperpigmentation – bleomycin JAAD 39:524–525, 1998; docetaxel Clin Exp Dermatol 33:276–277, 2008; bendamustine, peplomycin, trastuzumab Dermtol Ther (Heidelb) 5:253–264, 2015; doxorubicin J Cut Med Surg 20:481– 483, 2016 Flexural or intertriginous erythema/necrosis – dactinomycin AD 142:1660–1661, 2006; doxorubicin; bone marrow transplant regimen (cyclophosphamide, thiotepa, carboplatin) JAAD 64:1092– 1103, 2011; periaxillary erythema – pegylated doxorubicin JAAD 58:S44–46, 2008; cytarabine JAAD 73:821–828, 2015; ifosfamide, carboplatin, and etoposide chemotherapy JAAD 35:705–709, 1996; docetaxel – intertriginous painful bilateral drug rash Eur J Dermatol 26:427–443, 2016 Flushing – cisplatin JAAD 193–208, 2006; mithramycin JAAD 55:193–208, 2006; doxorubicin JAAD 55:193–208, 2006

Keratoacanthomas, eruptive – vermurafenib AD 148:363–366, 2012; and squamous cell carcinomas with BRAF inhibitors Leukonychia – chemotherapy-associated transverse striated leukonychia Lichenoid eruption – nivolumab, pembrolizumab JAAD 74:455–461, 2011; hydroxyurea JAAD 36:178–182, 1997 Lichen sclerosus et atrophicus, extragenital – nivolumab Clin Exp Dermatol 45:350–351, 2020; Clin Exp Dermatol 44:e22–23, 2019 Lipodermatosclerosis-like eruption, acute – gemcitabine JAAD Case Rep 3:190–195, 2017 Lipodystrophy, generalized – pembrolizumab BJD 182:477–480, 2020

Follicular papules – anti-epidermal growth factor receptor inhibitor J Clin Oncol 20:2240–2250, 2002; follicular papules and pustules – cetuximab BJD 161:515–521, 2009; JAAD 58:545–570, 2008; doxorubicin acral erythema with follicular accentuation AD 136:1475–1489, 2000; pityriasis rubra pilaris-like JAAD 65:452– 453, 2011; inflammatory folliculitis of scalp, upper body – taxanes J Natl Canc Inst 95:410, 2003

Livedo reticularis – gemcitabine JAAD 52:1009–1019, 2005; GCSF BJD 142:834–836, 2000

Folliculitis – trametinib, selumetinib (MEK inhibitors) JAMADerm 156:707–708, 2020

Morbilliform eruption (“drug rash”) – bortezomib JAAD 59:545–570, 2008; cladarabine JAAD 71:203–214, 2014; CTLA-4 inhibitors (ipilimumab, tremelimumab) JAAD 72:221–236, 2015;; JAAD 71:161–169, 2014; fludarabine JAAD 71:203–214, 2014; tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib JAAD 71:217–227, 2014; JAAD 58:545–570, 2008; MEK inhibitors (selumetinib, trametinib) JAAD 72:221–236, 2015; JAAD 71:217–227, 2014; pembrolizumab JAMADerm 151:1206–1212, 2015; pemetrexed JAAD 71:203–214, 2014; telaprevir JAMADerm 150:756–759, 2014; vemurafenib BJD 173:1024–1031, 2015; vincristine, vinblastine, vinorelbine, JAAD 71:203–214, 2014; MEK inhibitors (selumetinib, cobimetinib, trametinib) – generalized dusky drug rash JAMADerm 15:78–81, 2014

Granuloma annulare – immune checkpoint inhibitors J Eur Acad DV 32:e124–126, 2019; J Clin Exp Dermatol Res 6:256, 2015 Granulomatous skin reactions- nivolumab, pembrolizumab JAAD April 2020 Hair changes – texture, color or volume, dyspigmented Hair darkening – carbidopa Clin Exp Dermatol 14:317–318, 1989; inidinavir, bromocriptine, zidovudine, tamoxifen, erlotinib Hair lightening – cabozantinib JAMADerm 151:170–177, 2015; imatinib, tamoxifen, interferon-alpha Hand-foot syndrome secondary to chemotherapy – hand dermatitis with fissuring AD 147:1418–1423, 2011  Capecitabine  Cytarabine  Doxorubicin  5-flurouracil  Taxanes

Subacute cutaneous lupus erythematosus – capecitabine JAMADerm 156:103–104, 2020; capecitabine/fluorouracil JAAD 59:S4–6, 2008; docetaxel J Rheumatol 31:818–820, 2004; docetaxel, paclitaxel Eur J Dermatol 26:427–443, 2016; gemcitabine JAAD Case Rep 5:596–601, 2019

Nail toxicities – taxanes (paclitaxel, docetaxel); anthracycline based therapies; brittle nails, slow growth, dyschromia, painful subungual hemorrhage or abscesses, onycholysis, Beau’s or Mee’s lines, onychoschizia, onychomadesis, hyperpigmentation Necrosis – cisplatin Cancer Treatment Reports 67:199, 1983; methotrexate

Hyperhidrosis – dasatinib JCAD 10:25, 2017

Necrosis, cutaneous – methotrexate JAAD 8:677–679, 1983

Hyperpigmentation – of elbows, knees, hands; bleomycin AD 107:553–555, 1973

Neutrophilic eccrine hidradenitis – cytarabine JAAD 11:584–590, 1984; cytarabine facial plaque J Drugs Dermatol 12:231–232, 2013; topotecan J Dermatolog Treat 13:35–37, 2002; actinomycin plus vincristine; carbamazepine, granulocyte stimulating factor, BRAF inhibitors, NRTIs (nucleoside reverse transcriptase inhibitors (tenofovir and emtricitabine)

Hyperpigmentation, ashy gray – osimertinib (EGFR-TK1) JAAD Case Rep 6:86–88, 2020 Hyperpigmenttion, diffuse – bleomycin AD 107:553–555, 1973; busulfan JAAD 9:645–663, 1983; thiotepa JAAD 58:575–578, 2008 Hyperpigmentation, oral – busulfan, doxorubicin JAAD 56:828–834, 2007; 5-fluorouracil JAAD 56:828–834, 2007; tongue – cisplatin, ifosfamide, temozolomide, vincristine J Drugs Dermatol 12:223– 226, 2013; South Med J 72:1615–1616, 1979 Hyperpigmentation of palmar creases – bleomycin Jaad 40:367– 398, 1999; doxorubicin JAAD 39:524–525, 1998

Oral ulcerations/stomatitis – actinomycin D, adriamycin, amsacrine, bleomycin, busulfan, chlorambucil, cyclophosphamide, dactinomycin, daunorubicin, doxorubicin, fluorouracil, IL-2, mercaptopurine, methotrexate, mithramycin, mitomycin, nitrosoureas, procarbazine, vincristine JAAD 40:367–368, 1999 Palmar/plantar fibromatosis – vemurafenib

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Panniculitis – glatiramer acetate JAAD 55:968–974, 2006; GCSF BJD 142:834–836, 2000; granulomatous panniculitis – immune checkpoint inhibitors JAAD Case Reports 4:13–16, 2018; J Cut Pathol 44:1080–1086, 2017; JAMADerm 153:721–722, 2017; dasatinib JCAD 10:25, 2017; neutrophilic panniculitis – vemurafenib Dermatol Online J 19:16 April 15, 2013; all-trans retinoic acid JAAD 56:690–693, 2007; MINE chemotherapy Ann DV 128:756–758, 2001; topotecan and cyclophosphamide Ped Blood Cancer 44:98–99, 2005; neutrophilic panniculitis – imatinib and dasatinib Ann DV 138:135–139, 2011 Papillomas (benign warty dyskeratoma, verrucous keratosis) – dabrafenib, trametinib J Cut Med Surg 21:54–59, 2017 Paronychia, painful – docetaxel Cutis 71:229–232, 2003; pyogenic granuloma-like lesions – capecitabine BJD 147:1270–1272, 2002; gefitinib AD 148:1399–1402, 2012; JAAD 56:317–326, 2007; painful granulation tissue – cetuximab JAAD 69:463–472, 2013; BJD 161:515–521, 2009; JAAD 47:632–633m 2002; erlotinib JAAD 69:463–472, 2013; capecitabine JAMADerm 156:103–104, 2020; panitumumab Postepy Dermatol Alergol 34:418–428, 2017; neratinib J Dermatol Treat 30:487–488, 2019 Pemphigus vulgaris – D-penicillamine JAMADerm 247:2705–2707, 1982; radiation-induced Oxf Med Case Reports Jan 2020; Frontiers Immuno Jan 21, 2020; AD 126:1319–1323, 1990 Perforating dermatosis – interferon alpha Clin Exp Dermatol 45:349–350, 2020; Korean J Dermatol 46:788–791, 2008; telaprevir JAMADerm 150:1371–1372, 2014 Perianal dermatitis – sorafenib BJD 161:1045–1051, 2009; BJD 158:592–596, 2008; sunitinib AD 144:123–124, 2008 Photoeruption – farmorubicin Contact Dermatitis 30:303–304, 1994; 5-fluorouracil JAAD 40:367–398, 1999; hydroxyurea JAAD 51:293–300, 2004; capecitabine JAAD 47:453–2002; lichenoid – vandetanib JAAD Case Rep 1:141–143, 2015 Photorecall reaction – etoposide and cyclophosphamide Clin Exp Dermatol 18:452–453, 1993; etoposide and methotrexate JAAD 56:494–499, 2007; gemcitanine JAAD 56:494–499, 2007; methotrexate JAAD 58:903–905, 2008; AD 118:177–179, 1982 Photosensitivity – dasatinib Photodermatol Photoimmunol Photomed 36:172–178, 2020; JCAD 10:25, 2017; vemurafenib BJD 173L1024–1031, 2015 Phototoxicity – 5-fluorouracil JAAD 40:367–398, 1999; gefitinib JAAD 58:545–570, 2008; vinblastine JAAD 40:367–398, 1999;; AD 111:1168–1170, 1975; vemurafenib BJD 167:997–998, 2012 Pityriasis rosea-like eruption – imatinib JAAD 58:545–570, 2008; JAAD 53:S240–243, 2005; ibrutinib JAAD Case Rep 4:55–57, 2018 Pityriasis rubra pilaris-like – sorafenib JAAD 65:452–453, 2011 Pruritus – panitumumab Postepy Dermatol Alergol 34:418–428, 2017 Pseudocellulitis – gemcitabine Am J Ther 23:e321–323, 2016; JAAD Case Rep 1:178–181, 2015; Clin Inf Dis 45:e72–76, 2007; pemetrexed JAAD Case Rep 3:64–66, 2017; Am J Dermatopathol 39:e1–2, 2017 Psoriasiform dermatitis – mitomycin Arch Esp Urol 42:670–672, 1989; sorafenib J Drugs Dermatol 9:169–171, 2010; immune checkpoint inhibitors JAAD 80:990–997, 2019 Purpura – thrombocytopenia; chemotherapy-induced eccrine neutrophilic hidradenitis JAAD 40:367–398, 1999; purpuric eruption – lenalidomide JAAD 65:654–656, 2011 Radiation recall – docetaxel – butterfly rash BJD 153:441–443, 2005; pemetrexed JAAD 58:545–550, 2008; vemurafenib Dermatology 230:1–4, 2015; JAMADerm 149:855–857, 2013;

gemcitanine J Clin Oncol 18:693–694, 2000; idarubicin Gyn Oncol 57:266–269, 1995 Raynaud’s phenomenon – bleomycin as single agent of part of multiple drug chemotherapeutic regimen Cleve Clin J Med 61:195– 199, 1994 Red face – 5-fluorocytosine JAAD 8:229–235, 1983; 5-fluorouracil JAAD 17:192–197, 1987 Red nodules – face, trunk, neck and extremities – bortezomib JAAD 55:897–900, 2006; ulcerated and non-ulcerated JAAD 61:126–129, 2009 Retinoic acid syndrome – all trans retinoid acid – fever, respiratory distress, weight gain leg edema ,pleural and pericardial effusions, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum JAAD 56:690–693, 2007; Leuk Lymphoma 44:547–548, 2003 Sarcoid-like reaction – immune checkpoint inhibitors (PD-1, PD-L1 – cemiplimab, nivolumab, pembrolizumab, avelumab, durvalumab, atezolizumab, and CTLA-4 inhibitor – ipilimumab JAAD 81:1165–1175, 2019 Sclerodermoid changes – hands – bleomycin Clin Rheumatol 18:422–424, 1999; docetaxel; BJD 156:363–367, 2007; paclitaxel JAAD 59:545–570, 2008; BJD 156:363–367, 2007; edematous scleroderma BJD 164:1193–1195, 2011; peplomycin BJD 157:1213–1214, 2004; gemcitabine – leg edema followed by sclerodermoid changes JAAD 51:S73–76, 2004; radiation port JAAD 35:923–927, 2013 Scrotal dermatitis – sunitinib NEJM 359:975–976, 2008; capecitabine AD 147:1123–1124, 2011; cabozantinib JAMADerm 151:170–177, 2015; scrotal ulceration, all-trans retinoic acid; “malignant intertrigo” – a subset of toxic erythema of chemotherapy JAAD Case Rep 2:476–481, 2016; topical 5-fluorouracil JAAD 19:929–931, 1988 Seborrheic dermatitis – cetuximab, dasatinib, erlotinib, 5-fluorouracil, gefitinib, interferon-alpha, interleukin-2, sorafenib, sunitinib, thalidomide, vemurafenib JCAD 10:25, 2017; JAAD 60:299–305, 2009; BJD 161:1045–1051, 2009; AD 144:886–892, 2008 Seborrheic keratosis, inflamed – sorafenib JAAD 61:360–361, 2009; pemetrexed J Dermatol 44:602–603, 2017; cytarabine J Drugs Dermatol 3:565–566, 2004; gemcitabine Acta DV 28:185–186, 2019; Ann Bras Dermatol 84:410–413, 2009; docetaxel Acta DV 81:316–317, 2001 Supravenous erythema/hyperpigmentation (serpentine supravenous hyperpigmentation) NEJM 363:e8, 2010; bortezomib BJD 158:863– 864, 2008; bromodeoxyuridine JAAD 43:540–546, 2000; CHOP JAAD 43:540–546, 2000; docetaxel BJD 142:1069–1070, 2000; dacarbazine AD 118:1018–1019, 1982; fotemustine JAAD 39:839–842, 1998; vinorelbine JAAD 39:839–842, 1998; doxorubicin JAAD 43:540–546, 2000; 5-­fluorouracil JAAD 29:325–330, 1993; mitomycin JAAD 43:540–546, 2000; actinomycin plus vincristine Sweet’s syndrome – imatinib AD 141:369–370, 2005; lenalidomide – neutrophilic dermatosis JAAD 61:709–710, 2009; GCSF JAAD 50:49, 2004; JAAD 35;995–997, 1996; Ped Derm 18:417– 421, 2001; bortezomib Br J Hematol 131:142, 2005; gemcitabine JAAD 65:1236–1238, 2011; ipilimumab JAAD 70:e85–86, 2014 Thalidomide embryopathy – small malformed ears; Syndromes of the Head and Neck, 1990; p. 29 Tongue hyperpigmentation – cancer chemotherapy South Med J 72:1615–1616, 1979; cisplatin, ifosfamide, temozolomide, and vincristine J Drugs Dermatol 12:223–226, 2013

CLEFT LIP AND/OR PALATE (ASSOCIATED SKIN DISORDERS) Trichodysplasia of immunosuppression (trichodysplasia spinulosa, viral-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy) AD 142:1643–1648, 2006; JAAD 52:540–541, 2005 Ulcers of lower legs and feet hydroxyurea AD 143:1310–1313, 2007; gemcitabine Anticancer Drugs 14:829–832, 2003 Vasculitis, small vessel – bortezomib Br J Hematol 134:391–398, 2006; cisplatin BMC Cancer 17:831, Dec 6, 2017; panitumumab J Med Case Rep 13:13 Jan 16, 2019; blinatumumab JAAD Case Rep 3:395–397, 2017; oxaliplatin Case Rep Oncol 6:609–615, 2013; cytosine arabinoside Mayo Clin Proc 73:239–242, 1998; tamoxifen Ann Rheum Dis 64:3213–215, 2005; GCSF JAAD 31:213–215, 1994; large vessel vasculitis – GCSF (possibly docetaxel) Ann Rheum Dis 78 suppl 2:828, 2019 Vitiligo-like leukoderma – anti-PD-1 therapy ( nivolumab, pembrolizumab) JAAD 74:455–461, 2016; imatinib NEJM 360:160–169, 2009; imatinib – extension of vitiligo BJD 153:691–692, 2005; CTLA-4 inhibitors (ipilimumab, tremelimumab) JAAD 72:221–236, 2015; gefitinib Dermatol Online J Oct 16, 2013 Xerosis – asteatotic dermatitis – cetuximab BJD 161:515–521, 2009; JAAD 58:545–570, 2008; erlotinib JAAD 69:463–472, 2013; gefitinib JAAD 58:5445–570, 2008; AD 142:939, 2006; hydroxyurea AD 135:818–820, 1999; pemetrexed BJD 166:1359–1360, 2012; sorafenib JAAD 60:299–305, 2009; taxanes J Clin Oncol 13:2643– 2655, 1995

CHEST WALL TUMORS J Thoracic Cardiovasc Surg 111:96–105, 1996; Surg Gynecol Obstet 104:390, 1995

219

Metastases Osteosarcoma Plasmacytomas Pleomorphic sarcoma Post-radiation angiosarcoma Rhabdomyosarcoma Soft tissue sarcomas Squamous cell carcinoma J Med Case Rep 11:136, 2017

 LEFT LIP AND/OR PALATE C (ASSOCIATED SKIN DISORDERS) Bolognia, p.930, 2003 AEC (ankyloblepharon, ectodermal defects, cleft lip and palate) syndrome (Hay-Wells syndrome) – neonatal scalp erosions; similar to Rapp-Hodgkin with syndactyly, supernumerary nipple, lacrimal duct aplasia, scalp dermatitis, and recurrent scalp infections; erosive diaper dermatitis, fine papules of trunk with hypopigmentation, papular and pustular scalp dermatitis; hypoplastic nails, angular face with hypoplastic mandible (micrognathia), sparse wiry hair, patchy scarring alopecia, erythroderma with erosions; mutation in TP63 Ped Derm 28:313–317, 2011; Ped Derm 28:15–19, 2011; Ped Derm 26:617–618, 2009; Int J Dermtol 46:1196–1197, 2007; Ped Derm 22:415–419, 2005; BJD 94:277–289, 1976 Apert’s syndrome (acrocephalosyndactyly) – cleft soft palate Ped Derm 22:561–565, 2005

Anetodermic pilomatrixoma J Dtsch Dermatol Ges 16:640–643, 2018

Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Syndrome Ident 8:6–9, 1982

Chondromas

Beare-Stevenson cutis verticis gyrata syndrome

Enchondromas

Branchio-oculo-facial syndrome – autosomal dominant; congenital bilateral cervical ulcerations (bilateral ectopic thymus glands); congenital ulcerated neck mass (ectopic thymus), flattened nasal tip, pseudo-­cleft lip, posterior rotated ears, pre-auricular pit, cleft lip, microphthalmia, coloboma, nasolacrimal duct stenosis or atresia, dolichocephaly; mutation in TFAP2A (retinoic acid responsive gene) Ped Derm 29:759–761, 2012; Mol Vis 16:813–818, 2010; Arch Otolaryngol Head Neck Surg 128:714–717, 2002 (pseudocleft of upper lip, cleft-lip-­palate, and hemangiomatous branchial cleft) – atrophic neck lesions Ped Derm 29:383–384, 2012; Am J Med Genet 27:943–951, 1987

BENIGN TUMORS

Eosinophilic granuloma Fibromas Fibrous dysplasia Lipomas Neurilemmomas Neurofibromas Osteochondromas Osteomyelitis

Chondrosarcomas

Capillary malformations, branchial clefts, lip pseudoclefts, and unusual facies; anomalous retroverted ears, microphthalmia, cleft lip/palate JAAD 56:541–564, 2007; J Laryngol Otol 71:597–603, 1957

Clear cell carcinoma

Cleft lip/palate-ectodermal dysplasia

Dermatofibrosarcoma protuberans J Med Imaging Radiation Oncol 61:9–17, 2017

Dermal melanocytosis

MALIGNANT TUMORS Angiosarcoma Drug Discov Ther 10:114–116, 2016

Desmoid tumor Ewing’s sarcoma BMJ Case Rep Sept 27, 2017 Lymphoma Malignant fibrous histiocytoma

Disorganization syndrome – filiform worm-like projections, syndactyly, popliteal pterygium, polydactyly, cleft lip/palate; ear abnormalities Ped Derm 24:90–92, 2007; J Med Genet 26:417– 420, 1989 Ectodermal dysplasia and clefting – alopecia, tooth abnormalities, reticulated hyperpigmentation Ped Derm 28:707–710, 2011

220 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 EEC (ectrodactyly, ectodermal dysplasia, cleft lip and palate syndrome Am J Dis Child 120:160–163, 170 Encephaloceles Goldenhar syndrome – accessory tragi, auricular defects, hemifacial microsomia, epibulbar dermoids, mandibular hypoplasia, vertebral anomalies, genitourinary, cardiovascular, and gastrointestinal abnormalities, colobomas, cleft lip and palate Ped Derm 24:657– 658, 2007 Kabuki syndrome – vitiligo, developmental delay, short stature, congenital heart defects, skeletal defects, cleft palate, dental ­abnormalities, cryptorchidism, lip pits, prominent fingertip pads, autoimmune disorders, blue sclerae, prominent eyelashes, thinning of central eyebrows, protuberant ears; mutation in MLL2 Ped Derm 30:253–255, 2013; Amer J Med Genet 132A:260–262, 2005 Limb mammary syndrome – ectrodactyly, mammary gland/nipple hypoplasia, cleft palate Am J Hum Genet 64:481–492, 2001 Loeys-Dietz syndrome – joint hypermobility, thin skin with prominent veins, marfanoid body habitus, triangular delicate face, hypertelorism, bifid uvula or cleft palate, arterial dissection and rupture, prominent eyes, blue sclerae, aortic aneurysms, generalized arterial tortuosity, milia; type I and II TGF beta receptor JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005 Meckel syndrome – microcephaly, microphthalmia, congenital heart defects, postaxial polydactyly, polycystic kidneys, cleft lip/palate J Med Genet 8:285–290, 1971 Michelin tire baby syndrome – either nevus lipomatosis or diffuse smooth muscle hamartoma; degenerative collagen, scarring; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques; low set malformed ears with thickened helix and anti-helix; wide or depressed nasal bridge; epicanthal folds, hypertelorism, cleft palate, micro-ophthalmia or deep set eyes, flat or hypoplastic midface, short neck, decreased hearing, hypoplastic malformed genitalia, micrognathia, histologically increased periadnexal fat and subcutaneous fat and smooth muscle hamartomas; mental retardation, tendinous hyperlaxity, seizures, mastocytosis, complex malformations syndrome (bilateral calcaneovalgus deformity, cleft palate, inguinal hernia, hip deformity, clefting of lateral mouth commissures, shawl scrotum, absent foreskin; developmental delay, microcephaly, mental retardation Ped Derm 31:659–663, 2014JAAD 63:1110– 1111, 2010; Ped Derm 27:79–81, 2010; Ped Derm 24:628–231, 2007; Ped Derm 22:245–249, 2005; Ped Derm 20:150–152, 2003; BJD 129:60–68,1993; JAAD 28:364–370, 1993; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.308–309; Ped Derm 6:329–331, 1989; Am J Med Genet 28:225–226, 1987; AD 115:978–979, 1979; diffuse lipomatous hypertrophy AD 100:320– 323, 1969; generalized muscular nevus Ann DV 107:923–927, 1980 Nasal glioma Nail-patella syndrome Nevoid basal cell carcinoma syndrome – cleft lip and palate BJD 182:212–217, 2020; Ped Derm 32:141–142, 2015; AD 146:17–19, 2010 Oculocerebrotendinous syndrome Oral-facial-digital syndrome type 1(Papillon-Leauge-Psaume syndrome) – X-linked dominant; congenital facial milia which resolve with pitted scars; milia of face, scalp, pinnae, and dorsal hands; short stature, hypotrichosis with dry and brittle hair, short upper lip, hypoplastic ala nasi and lower jaw, pseudoclefting of upper lip, hooked pug nose, hypertrophied labial frenulae, bifid or multilobed tongue with small white tumors within clefts, ankyloglossia, multiple soft hamartomas of oral cavity, clefting of hard and soft palate, teeth

widely spaced with dental caries, trident hand or brachydactyly, syndactyly, clinodactyly, ulnar deviation of index finger, or polydactyly; hair dry and brittle, alopecic, numerous milia of face, ears, backs of hands, mental retardation with multiple central nervous system abnormalities, frontal bossing, hypertelorism, telecanthus, broad depressed nasal bridge; polycystic renal disease; combination of polycystic renal disease, milia, and hypotrichosis is highly suggestive of OFD 1 Ped Derm 27:669–670, 2010; JAAD 59:1050– 1063, 2008; Ped Derm 25:474–476, 2008; Ped Derm 9:52–56, 1992; Am J Med Genet 86:269–273, 1999; JAAD 31:157–190, 1994; Ped Derm 9:52–56, 1992; Pediatrics 29:985–995, 1962; Rev Stomatol 55:209–227, 1954 Pai syndrome – facial skin tags, nasal polyps, CNS lipomas Patau’s syndrome (non-mosaic trisomy 13) – parieto-occipital scalp defects, cleft lip/palate, Blaschko pigmentation, abnormal helices, low set ears, loose skin of posterior neck, simian crease of hand, hyperconvex narrow nails, polydactyly, microcephaly, microphthalmia, anophthalmia, severe central nervous system anomalies, congenital heart defects, holoprosencephaly; death in first year Ped Derm 31:580–583, 2014; Am J Med Genet 143A:1739–1748, 2007; Ped Derm 22:270–275, 2005 PHACES syndrome JAAD 55:1072–1074, 2006 Poikiloderma, alopecia, retrognathism, and cleft palate (PARC syndrome) Dermatologica 181:142–144, 1990 Popliteal pterygium (popliteal web) syndrome – autosomal dominant; bilateral popliteal pterygia, intercrural pterygium, hypoplastic digits, absence of labia majora, hypertrophied clitoris, cryptorchidism, bifid scrotum, valgus or varus foot deformities, syndactyly with or without polydactyly, cryptorchidism, umbilical or inguinal hernia, cleft scrotum, lower lip pits, cleft palate, mucous membrane bands (syngnathia) (fibrous bands connecting maxilla and mandible), eyelid adhesions (ankyloblepharon), hypertelorism, defect of alveolar ridge; mutation in IRF6 (this mutation also seen in van der Woude syndrome) Ped derm 28:333–334, 2011: J Med Genet 36:888–892, 1999; Int J Pediatr Otorhinolaryngol 15:17–22, 1988 Rapp-Hodgkin syndrome – autosomal dominant, hypohidrosis, keratoderma, onychodysplasia, hypodontia, trichodysplasia, midface hypoplasia, pinched nasal alae with low nasal bridge and high forehead, ear anomalies, hypospadias, short stature Ped Derm 22:415–419, 2005 Robert’s pseudothalidomide syndrome (hypomelia-hypotrichosisfacial hemangioma syndrome) (Roberts/SC phocomelia syndrome) – autosomal recessive; mid-facial port wine stain extending from forehead to nose and philtrum, cleft lip +/- cleft palate, sparse silver-blond hair, limb reduction malformation, characteristic facies, malformed ears with hypoplastic lobules, marked growth retardation JAAD 56:541–564, 2007; Clin Genet 31:170–177, 1987; Clin Genet 5:1–16, 1974 Segmental odontomaxillary dysplasia (HATS – hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin findings) – localized facial hypertrichosis, commissural lip cleft, hyperlinear palms, abnormal teeth, missing teeth, abnormal spacing Ped Derm 25:491–492, 2008 Trisomy 13 – total body milia; polydactyly, congenital cystic adenomatoid malformation, pulmonary hypertension, apnea, atrial septal defect, umbilical hernia, epilepsy, dislocated hip joint, ocular hypertelorism, microphthalmia, retinal hypoplasia, irideremia, small ears, deafness, broad flat nose, cleft palate, micrognathia, mental retardation Ped Derm 27:657–658, 2010

Coarse facies and Coarse Facial Skin 221 Van der Woude syndrome – autosomal dominant; hypodontia, lip pits, cleft lip and/or palate; mutation in interferon regulatory factor 6 (IRF6) Ped Derm 29:768–770, 2012 Waardenburg syndrome type 1 or 3 4p-syndrome (Wolf-Hirschhorn syndrome)

 OARSE FACIES AND COARSE C FACIAL SKIN Acromegaly Acta DV Croat 21:224–229, 2013 Beare-Stevenson syndrome – skin tags, cutis gyrata (furrowed skin), corrugated forehead, acanthosis nigricans, macular hyperpigmentation of antecubital and popliteal fossae, hypertelorism, swollen lips, swollen fingers, prominent eyes, ear anomalies, and umbilical herniation Ped Derm 20:358–360, 2003 Dermato-cardio-skeletal syndrome – autosomal recessive or X-linked; gingival hypertrophy, coarse facies, late eruption of teeth, loss of teeth, thick skin, acne conglobata, osteolysis, large joint flexion contractures, short stature, brachydactyly, camptodactyly, mitral valve prolapse, congestive heart failure Ped Derm 18:534– 536, 2001 Congenital hypertrichosis lanuginosa with gingival hyperplasia Ped Derm 10:263–265, 1993; profuse hypertrichosis of lower face, trunk, and extremities with acromegalic features Plast Reconstr Surg 27:608–612, 1962 Costello syndrome – coarse face with furrowed forehead and scalp, broad nose, wide anteverted nares, thick lips, dysplastic ears Ped Derm 30:665–673, 2013 Cretinism – coarse facial features, lethargy, macroglossia, cold dry skin, livedo, umbilical hernia, poor muscle tone, coarse scalp hair, synophrys, no pubic or axillary hair at puberty

hydrocephalus, valvular and ischemic heart disease, lower respiratory tract infections, adenotonsillar hypertrophy, otitis media, obstructive sleep apnea, diarrhea, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), widely spaced teeth, dolichocephaly, deafness, retinal degeneration, inguinal and umbilical hernias Ped Derm 37:369–370, 2020; Ped Derm 21:679–681, 2004 Job’s syndrome (hyper IgE syndrome) – autosomal dominant or sporadic; atrophoderma vermiculatum; coarse facial features with broad nose, rough thickened skin with prominent follicular ostia; papular and papulopustular folliculitis-like eruptions; oral candidiasis; chronic paronychia; cold abscesses of neck and trunk; otitis media common; mutation in STAT3 (transcription 3 gene activator and signal transducer JAAD 65:1167–1172, 2011 Leprechaunism (Donohue’s syndrome) – decreased subcutaneous tissue and muscle mass, characteristic facies, severe intrauterine growth retardation, broad nose, low set ears, hypertrichosis of forehead and cheeks, loose folded skin at flexures, gyrate folds of skin of hands and feet; breasts, penis, clitoris hypertrophic Endocrinologie 26:205–209, 1988 Lipoid proteinosis – hyaline-like material is PAS+ and diastase resistant JAAD 16:1193–1201, 1987; cobblestoned papules of dorsal fingers; mutation in ECM 1 (decreased ECM 1 protein) AD 144:1383–1388, 2008; Int J Derm 39:203–204, 2000; Acta Paediatr 85:1003–1005, 1996; JAAD 27:293–297, 1992; Virchows Arch Pathol Anat 273:285–319, 1929 Mucopolysaccharidoses (Hurler’s, Hurler-Schei, Sanfilippo, Morquio, Maroteaux-Lamy, Sly syndromes) – coarse facies Myhre syndrome – low birth weight, short stature, muscular build, limited joint mobility, cardiac defects, deafness, skeletal abnormalities, facial dysmorphism, thick skin, keratosis pilaris, coarse facies Myxedema Nevoid basal cell carcinoma syndrome

Erythropoietic protoporphyria

Pachydermoperiostosis J Dermatol 27:106–109, 2000

Fryns syndrome (cleft palate, diaphragmatic hernia, coarse facies, acral hypoplasia) – anonychia Clin Genet 35:191–201, 1989

Pachyonychia congenita

Fucosidosis type II Turk J Ped 56:430–433, 2014

Phymatous transformation of facial cutaneous vascular malformations JAMA Derm 149:368–369, 2013

Gangliosidosis – X-linked – gingival hypertrophy, macroglossia, coarse facies, micrognathia, loose skin, inguinal hernia, delayed growth, hepatosplenomegaly, neonatal hypotonia, delayed motor development Arch Pediatr 14:903–907, 2007; Ped Derm 18:534– 536, 2001 GAPO syndrome – begins at 1–2 years, growth retardation, alopecia, pseudoanodontia, ocular manifestations (optic atrophy), aged appearance with coarse facial features including frontal bossing, wide anterior fontanelle, saddle nose, micrognathia, protruding thick lips, low set ears, antimongoloid slant, prominent scalp veins, loose skin, small hands, lax joints Ped Derm 27:156– 161, 2010; Ped Derm 22:75–78, 2005; Am J Med Genet 19:209– 216, 1984; Odontol Tillster 55:484–493, 1947 GM1 gangliosidosis – generalized edema in infancy; coarse facies Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.132–133 Hunter’s syndrome – X-linked recessive; macrocheilia; reticulated 2–10mm skin colored papules over scapulae, chest, neck, arms; MPS type II; iduronate-2 sulfatase deficiency; lysosomal accumulation of heparin sulfate and dermatan sulfate; short stature, coarse facies, macroglossia, clear corneas (unlike Hurler’s syndrome), progressive neurodegeneration, communicating

Pallister Killian syndrome Mol Cytogenet 17:11, 2018

Rabson-Mendenhall syndrome (pineal hyperplasia syndrome – autosomal recessive, pineal hyperplasia, insulin-resistant diabetes mellitus, unusual coarse facies, dental precocity, hypertrichosis, acanthosis nigricans, and premature sexual development J Ped Surg 43:e21–26, 2008 Rudiger syndrome – thick single palmar crease; somatic retardation, flexion contractures of hands, small fingers and nails, ureterovesical stenosis, micropenis, inguinal hernias, coarse facies, cleft soft palate J Pediatr 79:977–981, 1971 Wiedemann-Steiner syndrome – hypertrichosis, prominent forehead, low hairline, small ears, hypertelorism, bushy eyebrows, localized thickened cutaneous plaques; dwarfism, peripheral corneal opacities, coarse facial features Winchester syndrome – annular and serpiginous thickenings of skin; arthropathy, gargoyle-like face, gingival hypertrophy, macroglossia, osteolysis (multilayered symmetric restrictive banding), generalized hypertrichosis, very short stature, thickening and stiffness of skin with annular and serpiginous thickenings of skin, multiple subcutaneous nodules JAAD 50:S53–56, 2004; J Pediatr 84:701–709, 1974; Pediatrics 47:360–369, 1971

222 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

COBBLESTONE APPEARANCE OF SKIN  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Blastomycosis-like pyoderma Botryomycosis JAAD 9:428–434, 1983 Condyloma acuminate – condylomata acuminate and molluscum contagiosum of vulva SKINmed 12:310–311, 2014

Dermatomyositis – cutaneous mucinosis JAAD 14:1–18, 1986

Cowpox – generalized cowpox in Darier’s disease – crusted papules, pustules, and vesicles; cobblestoned appearance; with massive periorbital edema BJD 164:1116–1118, 2011

Lupus erythematosus – discoid lupus erythematosus; papular and nodular mucinosis with SLE BJD 115:631–636, 1986

Generalized deep dermatophytosis (trichophytic granuloma) – Trichophyton rubrum AD 140:624–625, 2004

Pemphigus vegetans, Neumann type – giant cobblestoning with vegetative intertriginous plaques and blisters; oral bullae AD 145:715–720, 2009

Gianotti-Crosti syndrome – cobblestoned plaque of elbow; due to H1N1 influenza vaccine Ped Derm 28:595–596, 2011

Scleroderma – cobblestoning of dorsum of hand J Eur Acad DV 26:123–125, 2012

CONGENITAL LESIONS Chin hamartoma – multipapillated yellow-pink papules of chin with underlying infantile hemangioma; biopsy demonstrates sebaceous hamartoma of dermal fibroplasia with prominent vessels Ped Derm 37:78–85, 2020 Smooth muscle hamartoma

Leishmaniasis – post-kala azar dermal leishmaniasis; rippled skin BJD 143:136–143, 2000 Leprosy, lepromatous Lobo’s disease (lobomycosis) (keloidal blastomycosis) – Lacazia loboi; enlarged ear; cobblestoned appearance JAAD 77:197–218, 2017; JAAD 53:931–951, 2005; Cutis 46:227–234, 1990; Int J Derm 17:572–574, 1978 Molluscum contagiosum – in IRIS Cutis 89:212, 219–220, 2012; associated with B-cell lymphoma New England Dermatological Society Conference, Sept 15, 2007; in AIDS Ped Derm 20:436–439, 2003 Mycetoma JAAD 53:931–951, 2005;

DRUG-INDUCED Cyclosporine-induced folliculodystrophy – cobblestoning of nose, forehead, and glabella AD 148:219–223, 2012; cobblestoned follicular facial and earlobe papules (viral associated trichodysplasia) (trichodysplasia spinulosa); polyoma virus JAAD 50:318–322, 2004) JAAD 50:310–315, 2004 Rofecoxib – palmar wrinkling on exposure to water Ped Derm 19:353–355, 2002

Pitted keratolysis Protothecosis Cutis 99:80,87–88, 2017; BJD 146:713–715, 2002 Scabies, crusted BJD 158:1247–1255, 2008 Schistosomiasis – vulvar cobblestoned nodule Am J Surg Pathol 8:787–790, 1984 Small pox scarring Sporotrichosis – fixed cutaneous sporotrichosis – mountain range red plaque of face Cutis 96:218, 227–228, 2015

Vemurafenib – multiple nodules of cheeks; follicular plugging; exuberant seborrheic dermatitis-like hyperkeratosis of face; hand and foot reaction; diffuse spiny follicular hyperkeratosis; cobblestoning of forehead JAAD 67:1375–1379, 2012

Verrucae vulgaris, including flat warts in AIDS – HPV 5,6 or 11 Cutis 63:91–94, 1999; JAAD 23:978–981, 1990; warts in Netherton’s syndrome BJD 144:1044–1049, 2001; warts in GATA2 deficiency syndrome (MONOMAC syndrome) – personal observation

EXOGENOUS AGENTS

INFILTRATIVE

Aquagenic syringeal acrokeratoderma (aquagenic palmoplantar keratoderma, aquagenic keratoderma, aquagenic wrinkling of palms) BJD 167:575–582, 2012; AD 147:609–614, 2011; JAAD 59:S28–32, 2008;Ped Derm 24:564–566, 2007; JAAD 54:899–902, 2006; Ped Derm 23:39–42, 2006; BJD 152:394–395, 2005; Dermatology 204:8, 2002; JAAD 45:124, 2001

Amyloidosis – lichen amyloidosis J Dermatol 36:56–59, 2009; JAAD 37:923–928, 1997; facial cobblestoning Genetic Skin Disorders, Second Edition, 2010, pp.635–638; macular amyloid tumefactive (nodular)amyloidosis – uncommon variant of cutaneous localized amyloid; female predominance; deposits of amyloid in papillary and reticular dermis and subcutaneous fat; 15% of these patients actually have primary systemic amyloidosis AD 124:769–774, 1988; AD 102:8–19, 1970; BJD 82:129–136, 1970; amyloid elastosis (primary systemic amyloid) – white cobblestoned plaque around urethral meatus BJD 158:858–860, 2008; plaque type amyloid in B-cell lymphoma – personal observation; nodular amyloidosis – cobblestoned pink plaque of distal sole JAMADerm 153:79–80, 2017

Cold urticaria – positive ice cube test Exogenous ochronosis (grainy appearance) – topical application of hydroquinone JAAD 22:529–531, 1990 Podoconiosis – silica microparticles in sole; non-filiarial lymphedema JAAD 59:324–331, 2008; multilobulated hyperkeratotic nodules of feet; cobblestoned; bare feet exposed to red clay from alkaline volcanic rock BJD 168:550–554, 2013; JAAD 65:214–215, 2011 Tattoos (red) – pseudoepitheliomatous hyperplasia JAMA Derm 149:630–631, 2013

INFECTIONS AND/OR INFESTATIONS

Benign non-X histiocytosis – including xanthoma disseminatum, generalized eruptive histiocytoma, or indeterminate cell disorder JAAD 18:1282–1289, 1988 Colloid milium Indeterminate cell histiocytosis – widespread erythematous papulonodular eruption BJD 158:838–840, 2008

Actinomycetoma NEJM 372:264, 2015

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) Ped Derm 23:458–464, 2006

Aspergillosis – primary cutaneous aspergillosis; cauliflower-like lesion Am J Dermatopathol 23:224–226, 2001

Langerhans cell histiocytosis Clin Exp Dermatol 27:135–137, 2002; cobblestoned vulva JAAD 78:1035–1044, 2018

Cobblestone Appearance of Skin

223

Lichen myxedematosis (papular mucinosis, scleromyxedema) BJD 144:594–596, 2001; scleromyxedema – associated with paraproteinemia (IgG lambda light chains) (110 Kd 7S IgG); may be missing a portion of the Fc fragment; not usually associated with myeloma (those are IgG kappa light chains) JAAD 69:1062–1066, 2013; JAAD 69:66–72, 2013; Cutis 39:219–223, 1987; facial cobblestoning BJD 157:1058–1060, 2007;

Vernal keratoconjunctivitis – confluent cobblestoned papillae in upper palpebral conjunctivae NEJM 370:1636, 2014

localized lichen myxedematosus (papular mucinosis) in morbid obesity BJD 148:165–168, 2003

Aquagenic wrinkling of the palms in cystic fibrosis AD 145:1296– 1299, 2009; Ped Derm 26:660–661, 2009; Australas J Dermatol 49:19–20, 2008; Dermatology 216:222–226, 2008; AD 141:621– 624, 2005; Med Biol Illustr 25:205–210, 1975; Lancet ii:358–359, 1974; aquagenic keratoderma without cystic fibrosis

Mastocytosis – crocodile-like pachydermic skin; mastocytoma (nodular mastocytoma) JAAD 55:347–349, 2006; BJD 144:208– 209, 2001; BJD 103:329–34, 1980; diffuse cutaneous mastocytosis (xanthelasma) (red leathery skin) – scotch grain leather appearance Ped Derm 28:542–546, 2011; AD 146:557–562, 2010; J Investig Dermatol Symp Proc 6:143–147, 2001; BJD 144:682–695, 2001; leonine facies

METABOLIC Anasarca – with bullae

Diabetic finger pebbling (Huntley’s papules) (finger pebbles) Cutis 69:298–300, 2002; JAAD 14:612–617, 1986 Miliaria profunda – gooseflesh and hypohidrosis AD 143:1323– 1328, 2007

Med Chir Trans 66:329–347, 1883

Myxedema – personal observation

Mucinosis of obesity – personal observation

Nephrogenic systemic fibrosis – gadolinium exposure from MRIs in end stage renal disease; rippled sclerodermoid skin (peau d’orange) BJD 165:828–836, 2011

Papular mucinosis – localized papular mucinosis associated with IgA nephropathy; cobblestoned shiny grouped follicular papules of the neck AD 147:599–602, 2011 Primary cutaneous mucinoses include acral mucinosis, self healing juvenile cutaneous mucinosis, focal cutaneous mucinosis, lichen myxedematosus, and cutaneous mucinosis of infancy JAAD 28:797–798, 1993; self-healing juvenile cutaneous mucinosis – “corrugated” appearance of papules; rapid onset asymptomatic papules in linear arrays; face, neck, scalp, trunk, and thighs; nodules on face and joints with arthritis underlying joints JAAD 11:327–332, 1984 Rosai-Dorfman disease – multinodular tumor with cobblestoning AD 142:428–430, 2006; BJD 149:672–674, 2003 Scleredema Aust Fam Physician 42:876–877, 2013 Verruciform (verrucous) xanthoma – gingiva and alveolar ridge are most common locations; may be found on genitalia or extragenital sites; isolated flat papillomatous (papillated) plaque; no associated ­hyperlipidemia; mimics verrucous carcinoma or squamous cell carcinoma of genitalia; may be seen with ILVEN or in CHILD syndrome Ped Derm 37:355–347, 2020; JAAD 42:343–347, 2000; Cutis 51:369–372, 1993 Xanthoma disseminatum – normolipemic mucocutaneous xanthomatosis; yellow to orange papules in flexures and intertriginous areas; internal involvement of pituitary, bone marrow, brain, respiratory system, heart, kidney, pancreas, lymph nodes, uterus, muscles, and mucous membranes; associated with diabetes insipidus; blindness, cerebellar ataxia, and internal hydrocephalus due to lesions on or near the hypophysis; monoclonal gammopathy JAMADerm 152:715–716, 2016; BJD 150:346–349, 2004; JAAD 23:341–346, 1990

INFLAMMATORY Chronic peristomal papillomatous dermatitis BJD 143:1248–1260, 2000 Crohn’s disease – peristomal Crohn’s disease BJD 143:1248–1260, 2000 Eosinophilic fasciitis Curr Rheum Reports 4:113, 2002; Rheum Dis Clin North Am 21:231, 1995; Assoc Am Physicians 88:70, 1985 Erythema multiforme – personal observation Hidradenitis suppurativa – giant vulva with cobblestoning – severe lymphedema with lymphangiectasias JAAD 64:1223–1224, 2011 Lymphocytoma cutis

Osteomas – multiple miliary facial osteomas (miliary osteoma cutis) Cutis 69:383–386, 2002; platelike osteoma cutis AD 143:109–114, 2007 Porphyria – erythropoietic protoporphyria BJD 155:574–581, 2006; Eur J Pediatr 159:719–725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751–766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976; porphyria cutanea tarda, variegate porphyria – personal observation Pretibial myxedema – occurs in 1–10% of patients with Grave’s disease. Often associated with exophthalmos NEJM 352:918, 2005; JAAD 14:1–18,1986; AD 117:250–251, 1981; elephantiasic pretibial myxedema JAAD 46:723–726, 2002 Thyroid acropachy Xanthomatosis – type II hypercholesterolemia – including tuberous xanthomas of the eyelids Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.139

NEOPLASTIC Acquired digital fibrokeratoma JAAD 48:S67–68, 2003 Angiomyxomas AD 144:1217–1222, 2008 Bowen’s disease, vulvar Ann DV 109:811–812, 1982; Cancer 14:318–329, 1961; velvety plaque of palm JAAD 62:356–357, 2010 Bowenoid papulosis (vulvar)JAAD 29:644–646, 1993 Buschke-Lowenstein tumor (giant condylomata acuminate) JAMA Derm 149:1068–1070, 2013 Chordoma (sacral tumor) – non-tender, firm, flesh colored smooth surfaced nodules; may be painful; tumors arising from the notochord (embryonic precursor of axial skeleton); localize in midline; sacrococcygeal (50%), non-sacral vertebrae (15%), and at base of skull (35%); metastases may occur JAAD 29:63–66, 1993 Clear cell acanthoma (velvety plaque) – usually on legs; 3–20 mm. JAAD 44:314–316, 2001; JAAD 21:313–315, 1989 Connective tissue nevus Ped Derm 11:84–85, 1994; Curr Prob in Derm 8:137–188, 1996; disseminated collagenomas; connective tissue nevus with elastorrhexis or upper chest – skin colored or hypopigmented or yellow papules, plaques, nodules in cobblestoned pattern Ped Derm 32:518–521, 2015 Dermatofibrosarcoma protuberans – starts as indurated dermal plaque which becomes cobblestoned or multilobulated; trunk more

224 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 common than proximal extremities or head and neck JAAD 20:151–152, 1989 Eccrine porocarcinoma – cobblestoned red plaque JAAD 76:S73– 75, 2017 Eccrine syringofibroadenoma – acrosyringeal hamartoma; may be solitary, dermatomal or multiple nevoid tumors; associated with other eccrine tumors or ectodermal dysplasia syndromes; face, back, abdomen, buttock, or extremities; tapioca pudding-like surface; 0.1–25 cm. papules, nodules, fleshy, spongy, or verrucous plaques; AD 126:945–949, 1990 Epidermal nevus – systematized (ichthyosis hystrix); with woolly hair nevus – personal observation

Nevus sebaceus – personal observation Onychomatricoma – parallel white and yellow nail bands with thickening of the nail plate; multiple subungual perforations (cobblestoned appearance) JAAD 76:S19–21, 2017 Osteoma cutis with unilateral linear basal cell nevus – may be seen as multiple primary osteomas of the face of women, diffuse multiple osteomas of the extremities, Albright’s hereditary osteodystrophy (short stature, round face, absence of several knuckles with or without mental retardation), fibrodysplasia ossificans progressiva (ossification of fascia, aponeurosis, and muscular structures, microdactyly) JAAD 20:973–978, 1989 Papillomatosis cutis carcinoides Cutis 62:77–80, 1998

Extramammary Paget’s disease – cobblestoned scrotum BJD 164:200–203, 2011

Penile carcinoma with HPV 18 – either HPV 16 or 18 may be implicated in penile carcinoma JAAD 20:887–889, 1989

Folliculosebaceous cystic hamartoma – cobblestoned umbilicated skin colored nodules covering half of scrotum BJD 157:833–835, 2007; J Dermatol 33:191–195, 2006

Congenital rhabdomyosarcoma – multilobulated cobblestoned nodule of bridge of nose Ped Derm 36:747–749, 2019

Granular cell tumor of the vulva – single or multiple; slow growing solitary nodules or plaques with smooth or hyperkeratotic surface; tongue (35%), head and neck (50%), vulva (5.3%) Ped Derm 10:153–155, 1993 Grzybowski’s eruptive keratoacanthomas – non-familial; crops of pruritic lesions on head and neck; numerous lesions under 1 cm; heal with scarring JAAD 21:1023–1024, 1989 Hair follicle hamartoma – personal observation Hamartomas – multiple hamartomas of the ears JAAD 24:293–295, 1991 Hidrocystomas, multiple – personal observation Kaposi’s sarcoma Dermatol Clin 24:509–520, 2006 Keloids NEJM 372:1453, 2015 Leukemia – adult T-cell leukemia (HTLV-1 leukemia/lymphoma); Southwest Japan, Caribbean, Southeast US, South America, Africa; all areas where HTLV-1 is endemic; 3/4 patients have cutaneous involvement which resembles that of CTCL; acute and progressive course; ATL cells are suppressor T cells and express Tac (IL-2R) on cell surface AD 134:439–444, 1998; JAAD 34:69–76, 1996; BJD 128:483–492, 1993; Am J Med 84:919–928, 1988; JAAD 13:213– 219, 1985 Lymphoma – cutaneous T-cell lymphoma JAAD 23:653–662, 1990; Hodgkin’s disease AD 116:1038–1040, 1980; HTLV-1 l­eukemia/ lymphoma – multiple papules, cobblestoned skin JAMADerm 151:443–444, 2015; primary cutaneous diffuse large B-cell lymphoma, leg type BJD 157:1205–1211, 2007; primary cutaneous epidermotropic CD8+ T-cell lymphoma – mixture of patches, plaques, papulonodules with central ulceration, necrosis, and hemorrhage JAAD 62:300–307, 2010 Melanocytic nevus – congenital melanocytic nevus – cobblestoned, cerebriform, localized hypertrichosis, hyperpigmented discrete annular plaque JAAD 68:441–451, 2013 Mesothelioma, metastatic JAAD 54:563–565, 2006 Metastases – transitional cell carcinoma metastatic to scrotum demonstrating cobblestoned papules AD 143:1067–1072, 2007; bile duct carcinoma (rippled appearance) – percutaneous biliary catheterization may disseminate tumor cells along the catheter tract JAAD 25:848–849, 1991 Mucinous nevus BJD 148:1064–1066, 2003

Sebaceous gland hypertrophy of labia minora Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 104 Seborrheic keratosis Smooth muscle hamartoma Spindle cell hemangioendothelioma – multiple subcutaneous nodules; palmar giant cobblestoning; hypertrophy of hand Cutis 79:125–128, 2007 Spitz nevus Great Cases from the South; AAD Meeting; March 2000 Squamous cell carcinoma – vulvar squamous cell carcinoma – papular and polypoid lesions; verrucous white cobblestoned plaque JAAD 66:867–880, 2012 Syringocystadenoma papilliferum – papillomatous papulonodule Cutis 88:120, 133–134, 2011 Syringomas – hypertrophic, cobblestoned labia majora Ped Derm 23:369–372, 2006; ; giant cobblestoned vulvar nodules SKINmed 11:305–306, 2013 Trichoblastoma AD 137:219–224, 2001 Trichodiscomas – multiple agminated trichodiscomas of earlobe JAAD 49:729–730, 2003 Trichoepitheliomas, multiple JAMADerm 155:1070, 2019; Am J Dermatopathol 24:402–405, 2002; of nose AD 87:102–114, 1963 Verrucous carcinoma – personal observation Xanthogranulomas – generalized lichenoid juvenile xanthogranulomas Br J Derm 126:66–70,1992

PARANEOPLASTIC Acanthosis nigricans, malignant – velvety dorsal fingers, malignant acanthosis nigricans and tripe palms; cobblestoned lips, buccal mucosa, and tongue – pancreatic carcinoma JAMADerm 155:1069, 2019; NEJM 370:558, 2014; Cutis 89:14–16, 2012; Cutis 78:37–40, 2006; tripe palms with cobblestoned lips – urogenital cancer JAMADerm 151:1381–1383, 2015 Bazex syndrome BJD 103:301–306, 1980 Necrobiotic xanthogranuloma Cutis 59:333–336, 1997 Tripe palms NEJM 370:558, 2014; JAAD 54:745–762, 2006; J Clin Oncol 7:669–678, 1989; JAAD 16:217–219, 1987; with psoriasis Clin Exp Dermatol 5:181–189, 1980

Nevoid epidermoid cysts Nevus lipomatosis superficialis Ped Derm 20:313–314, 2003; Arch Dermatol Syphilol 130:327, 1921

PHOTODERMATOSES Actinic damage Clin Dermatol 32:752–762, 2014

Cobblestone Appearance of Skin Actinic reticuloid (chronic actinic dermatitis) – chronic photosensitivity disorder associated with CTCL; sensitive to UVB JAAD 21:1134–1137, 1989; JAAD 38:877–905, 1998; Sem Derm 161, Sept 1982; AD 115:1078–1083, 1979

225

Hyperkeratosis of the nipple and areola (hyperkeratosis areolae mammae) JAAD 41:274–276, 1999; Eur J Dermatol 8:131–132, 1998 JAAD 13:596–598, 1985; AD 126:687, 1990; estrogen-induced Cutis 26:95–96, 1980 Ichthyosis hystrix (Lambert type) JAAD 36:646–647, 1997

PRIMARY CUTANEOUS DISEASE

Lichen nitidus – personal observation

Acantholytic dermatosis of the vulvo-crural area – vulvar papules, cobblestoning of the vulva and thighs Cutis 67:217–219, 2001

Lichen planus

Acanthosis nigricans, pseudo-acanthosis nigricans, benign Acquired plantar hyperkeratosis Acquired epidermodysplasia verruciformis in AIDS – personal observation Acrokeratoelastoidosis of Costa – personal observation Actinic rhinophyma – personal observation Alopecia mucinosa – personal observation Angiolymphoid hyperplasia with eosinophilia – ear lesions AD 143:841–844, 2007; BJD 81:1–14, 1969 Atopic dermatitis – cobblestoning of dorsal hands Ped Derm 29:395–402, 2012 Confluent and reticulated papillomatosis – personal observation Darier’s disease JAAD 27:40–50, 1992 Epidermolysis bullosa – dystrophic epidermolysis bullosa pruriginosa (epidermolysis bullosa pruriginosa) – red, crusted, and lichenified papules BJD 159:464–469, 2008; BJD 130:617–625, 1994

Lichen simplex chronicus Cutis 78:101–102, 2006; of vulva Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 158; nodular lichen simplex chronicus of scrotum BJD 144:915–916, 2001 Mal de Meleda (recessive transgressive palmoplantar keratoderma) – lichenoid cobblestoned plaques on knees Ped Derm 14:186–191, 1997 Ofuji’s disease (eosinophilic pustular folliculitis) – crops of follicular papules and pustules on face, trunk, and extremities; leukocytosis with eosinophilia and elevated IgG, IgA, and IgE JAAD 12:268–273, 1985 Papillary dermal elastolysis J Cutan Pathol 36:1010–1013, 2009; J Dermatol 34:709–711, 2007; J Eur Acad Dermatol Venerol 51:165–185, 2004 Papular acantholytic dyskeratosis of the vulva – personal observation Perforating granuloma annulare AD 137:1647–1652, 2001 Perianal pseudoverrucous papules and nodules AD 128:24–242, 1992

Epidermolytic hyperkeratosis AD 130:1026–1033, 1994

Pityriasis rubra pilaris in AIDS JAAD 27:260–262, 1992

Erythema elevatum diutinum – cobblestoned multilobular nodules of foot in HIV disease AD 144:933–938, 2008

Progressive symmetric erythrokeratoderma – personal observation

Erythema of Jacquet – perianal dermatitis in adult with urinary incontinence Cutis 82:72–74, 2008; resembling keloids AD 144:933–938, 2008 Excess skin folds with cobblestone appearance in:  Dermatosparaxis AD 129:1310–1315, 1993  Cutis laxa – autosomal dominant (good prognosis), autosomal recessive (one form with severe cardiorespiratory symptoms), X-linked recessive (X-linked Ehlers-Danlos syndrome-joint laxity, bladder diverticula, hernia, cranial occipital exostoses), or acquired (may follow febrile illnesses, seen in offspring of mothers with cystinuria taking penicillamine; also DeBarsy syndrome, Patterson syndrome, wrinkly skin syndrome, geroderma osteoplastica, pseudoxanthoma elasticum, SCARF syndrome (skeletal abnormalities, ambiguous genitalia, craniostenosis, retardation, and facial abnormalities), amyloidosis and plasma cell dyscrasia) AD 129:757–762, 1993 Fibroelastolytic papulosis – skin colored papules with cobblestoning of face and neck; possibly same as white fibrous papulosis of neck or PXE-like papillary dermal elastolysis AD 148:849–854, 2012 Folliculitis decalvans – personal observation

FOX-FORDYCE DISEASE

Pseudoepitheliomatous keratotic and micaceous balanitis Cutis 35:77–79, 1985 Pseudoxanthoma elasticum-like papillary dermal elastolysis – side of neck, axilla; post-menopausal and elderly women JAAD 67:128–135, 2012; JAAD 51:165–185, 2004 Rhinophyma Scrotal glans penis Int J Derm 36:762–763, 1997 Striae atrophicae Terra firme – personal observation Vohwinkel’s palmoplantar keratoderma White fibrous papulosis of the neck (fibroelastolytic papulosis) – cobblestoning with 2–4mm skin colored papules JAAD 51:958–964, 2004; Int J Derm 35:720–722, 1996; JAAD 20:1073–1077, 1989 X-linked ichthyosis – cobblestoned hyperkeratotic lesions of dorsal feet Cutis 102:402,414–415, 2018

SYNDROMES Birt-Hogg-Dube syndrome – fibrofolliculomas; autosomal dominant; fibrofolliculomas (of mesodermal and epithelial origin), trichodiscomas (of mesodermal origin), and acrochordons on face, neck, scalp, and upper trunk; differential diagnosis includes multiple trichoepitheliomas (autosomal dominant),

Granular parakeratosis Ped Derm 20:215–220, 2003

Cowden’s syndrome (autosomal dominant), fibrofolliculomas (autosomal dominant), trichodiscomas (autosomal dominant), perifollicular fibromas, and adenoma sebaceum (autosomal dominant); association with renal cell carcinoma JAAD 16:452–457, 1987

Hailey-Hailey disease JAAD 26:951–955, 1992

Brooke-Spiegler syndrome JAMA Derm 149:22–228, 2013

Genitoperineal papular acantholytic dyskeratosis – hypertrophic cobblestoned vulva; perianal hypertrophic dermatitis; mutation in ATP2C1 BJD 166:210–212, 2012

226 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Buschke-Ollendorff syndrome – autosomal dominant; skin-colored to yellow papules; loss of function mutation in LEMD3 (inner nuclear membrane protein that antagonizes transforming growth factor beta and bone morphogenic protein signaling) AD 146:63–68, 2010; Ped Derm 22:133–137, 2005; Nat Genet 36(11):1213–1218, 2004; JAAD 49:1163–1166, 2003; BJD 144:890–893, 2001; Derm Wochenschr 86:257–262, 1928 Centrofacial trichoblastomatosis – leonine facies, cobblestoning of glabella and nose, eyebrow alopecia BJD 169:224–226, 2013 CHILD syndrome – verruciform xanthoma; giant red plaque of lateral foot; cobblestoned, verrucous giant tumor; enlarged foot; exophytic mass; X-linked dominant; mutation in NSDHL (NAD(P)dependent steroid dehydrogenase-like gene) Cutis 88:269–272, 2012; Ped Derm 27:551–553, 2010; Ped Derm 15:360–366, 1998; verruciform xanthoma – blsschko red cobblestoned verrucous hypertrophic plaque of vulva with linear extension onto leg Ped Derm 32:135–137, 2015 Congenital erosive and vesicular dermatitis with reticulate scarring – cobblestoned scars AD 121:361–367, 1985 Cowden’s syndrome (multiple hamartoma syndrome) – trichilemmomas coalescing around the eyes and mouth JAAD 11:1127–1141, 1984; AD 114:743–746, 1978 Epidermodysplasia verruciformis JAAD 32:523–524, 1995; giant cobblestoning of palms BJD 155:218–220, 2006 Goltz’s syndrome – symmetric soft spongy plaques; personal observation Hidrotic ectodermal dysplasia (Clouston’s syndrome) – pebbly cobblestoned fingertips; alopecia, thick nails Ped Derm 27:651–652, 2010 Hunter’s syndrome(mucopolysaccharidosis IIb) – X-linked recessive; scapular papules; cobblestoned skin colored papules also of posterior axillary lines, upper arms, forearms, chest, outer thighs; decreased sulfoiduronate sulfatase; skin colored papules overlying scapulae; linear and reticular patterns; also on shoulder, upper arms and chest, and lateral thighs; rough thickened skin, coarse scalp hair, and hirsutism; coarse facies with frontal bossing, hypertelorism, and thick tongue; dysostosis multiplex; hunched shoulders and characteristic posturing; hepatosplenomegaly; upper respiratory infections due to laryngeal or tracheal stenosis; mental retardation; deafness; retinal degeneration and corneal clouding; umbilical and inguinal hernias; thickened heart valves lead to congestive heart failure; iduronate-2-sulfatase deficiency Ped Derm 33:594–601, 2016; BJD 159:249–250, 2008; BJD 148:1173–1178, 2003; Clin Exp Dermatol 24:179–182, 1999; AD 134:108–109, 1998; JAAD 39:1013–1015, 1998; Ped Derm 15:370–373, 1998; Am J Med Genet 47:456–457, 1993; Ped Derm 7:150–152, 1990 Hurler’s syndrome – scapular papules; pebbling of skin between scapulae or on deltoid region; also posterior axillary lines, upper arms, forearms, chest, outer thighs Acta Paediatr 41:161–167, 1952 Hutchinson-Guilford syndrome – soft and pebbly nodules HID syndrome (hystrix-like ichthyosis with deafness) – autosomal dominant; shark-skin appearance, sensorineural deafness, spiky and cobblestoned hyperkeratosis, neonatal erythroderma, scarring alopecia, occasional punctate keratitis; probably variant of KID syndrome with mutation of connexin 26 (gap junction protein) BJD 146:938–942, 2002 Ichthyosis prematurity syndrome(“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; erythrodermic infant with caseous vernix-like desquamation; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine

scaling of scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin (thick vernix caseosa-like covering) (hyperkeratotic scalp)neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4 (FATP4) JAAD 66:606– 616, 2012; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008; hyperkeratotic cobblestoning of back of neck, flexural hyperpigmented follicular hyperkeratosis, intertriginous hyperpigmentation and hyperkeratotic plaques in the adult JAMADerm 152:1055–1058, 2016 Juvenile hyaline fibromatosis – autosomal recessive; ages 2 to adult; myofibroblastic origin; face, scalp, and back; joint deformities, gingival hyperplasia, and papillomatous perianal lesions Ped Derm 6:68, 1989 Keratitis, ichthyosis, deafness (KID) syndrome – autosomal dominant; cobblestoned palmoplantar keratoderma; sporadic; red face with papillomatous hyperkeratosis of face, scalp, trunk, and extremities; reticulated severe diffuse hyperkeratosis of palms and soles (grainy leather-like surface), well marginated, serpiginous erythematous verrucous plaques, perioral furrows, leukoplakia, sensory deafness, photophobia with vascularizing keratitis, blindness; inflammatory nodules of scalp; connexin 26 (GJB2) mutations Ped Derm 29:349–357, 2012; AD 148:1199–1204, 2012; BJD 156:1015–1019, 2007; Ped Derm 23:81–83, 2006; JAAD 23:385–388, 1990; AD 123:777–782, 1987; AD 117:285–289, 1981 Lipoid proteinosis – hyaline-like material is PAS+ and diastase resistant JAAD 16:1193–1201, 1987; cobblestoned papules of dorsal fingers; mutation in ECM 1 (decreased ECM 1 protein) AD 144:1383–1388, 2008; Int J Derm 39:203–204, 2000; Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.177; Acta Paediatr 85:1003–1005, 1996; JAAD 27:293–297, 1992; Virchows Arch Pathol Anat 273:285–319, 1929 Michelin tire baby syndrome Multicentric reticulohistiocytosis Clin in Derm 11:107–111, 1993; JAAD 11:713–723, 1984 Netherton’s syndrome – personal observation Neurofibromatosis type I – elephantiasis neurofibromatosa; personal observation Pachydermoperiostosis – cobblestoned palmoplantar hyperkeratosis J Dermatol 27:106–109, 2000 Perioral cobblestoning, ichthyosis and deafness AD 124:102–106, 1988 Proteus syndrome – cerebriform hyperplasia or connective tissue nevus of soles; hemihypertrophy, port wine stains, macrodactyly; mosaic activating mutation of AKT1 J Drugs in Dermatol 12:586– 587, 2013; NEJM 365:611–619, 2011; AD 140:947–953, 2004; JAMA 285:2240–2243, 2001; Ped Derm 6:344–345, 1989; Eur J Pediatr 140:5–12, 1983; Birth Defects 15:291–296, 1979 Pseudoxanthoma elasticum – linear and reticulated cobblestoned yellow papules and plaques BJD 161:635–639, 2009; JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; AD 124:1559, 1988; PXE and acrosclerosis Proc Roy Soc Med 70:567–570, 1977 ROMBO syndrome – autosomal dominant; grainy skin, cobblestoning due to aggregated milia of forehead; multiple basal cell carcinomas, vermicular atrophoderma, trichoepitheliomas, hypotrichosis, cyanosis of hands and feet; differential diagnosis includes Bazex syndrome (follicular atrophoderma, hypotrichosis, basal cell carcinomas), Rasmussen syndrome (milia, trichoepitheliomas, and cylindromas), and Birt-Hogg-­Dube BJD 165:30–34, 2011; JAAD 28:1011–1014, 1993 Sweet’s syndrome NEJM 382:1543, 2020

Cobblestone Appearance of the Oral Mucosa 227 Tuberous sclerosis – connective tissue nevus JAMADerm 153:660– 665, 2017; adenoma sebaceum; personal observation

Port wine stain (nevus flammeus) JAMADerm 150:1336–1340, 2014;

TOXINS

JAAD 37:523–549, 1997; old port wine stain AD 120:1453–1455, 1984; JID 74:154–157, 1980; port wine stain with epithelial and mesenchymal hamartomas JAAD 50:608–612, 2004

Eosinophilic myalgia syndrome – l-tryptophan Am J Med 88:542– 546, 1990

TRAUMA Radiation – lymphangiectasia after breast cancer radiation – personal observation

Tufted angioma AD 142:745–751, 2006 Varicosities – chronic congestive heart failure Venous stasis ulceration (chronic venous insufficiency) and stasis dermatitis – cobblestoning and papillomatosis around ulcer Verrucous hemangioma Cutis 99:158,169, 2017

Scar

Verrucous localized lymphedema of penis, scrotum, vulva, pubis – polypoid, verrucous, cobblestoned lesions JAAD 71:320– 326, 2014

Verrucous hyperplasia of the stump

Vulvar papillomatosis (angiofibromas) (vestibular papillae) – papules

Verruciform xanthoma – red-orange plaque; multilobulated, vegetative, cobblestoned; perigenital; seen in KID, CHILD, syndromes and recessive dystrophic epidermolysis bullosa; usually at site of friction or frequent trauma Ped Derm 37:176–179, 2020 Warm weather immersion foot – wrinkled appearance Dermatol Clinics 17:1–17, 1999 Wrestler’s ear

VASCULAR

COBBLESTONE APPEARANCE OF THE ORAL MUCOSA  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – cobblestoning of lips

Acquired progressive lymphangioma Cutis 93:316–319, 2014

Dermatitis herpetiformis – maculopapular lesions on alveolar mucosa

Acral pseudolymphomatous angiokeratoma – cobblestoned pink and purpuric plaque of heel JAAD 76:S25—27, 2017

Desquamative gingivitis

Elephantiasis verrucosa nostra (nostras verrucosa) – lymphostasis verrucosa cutis; chronic lymphedema – congenital, inherited, acquired Int J Surg Case Rep 65:127,-130, 2019; massive localized lymphedema J Clin Pathol 62:808–811, 2009associated with obesity, infection, chronic venous insufficiency; cobblestoning, edema, hyperkeratotic plaques of lower legs and feet NEJM 370:69, 2014; JAAD 64:1104–1110, 2011; Cutis 62:77–80, 1998; elephantiasis nostras of penis AD 137:1095–1100, 2001; lymphedema of vulva Arch Pathol Lab Med 124:1697–1699, 2000; Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 222 Glomangioma JAAD 45:239–245, 2001 Glomuvenous malformation – blue-purple nodules with pebbly surface; loss of function of glomulin JAAD 65:893–906, 2011; Ped Derm 25:381–382, 2008; JAAD 56:353–370, 2007; AD 140:971– 976, 2004 Hemolymphangioma Infantile hemangioma Ped Derm 28:502–506, 2011 Klippel-Trenaunay-Weber syndrome with lymphangiomas Lymphangiectasia (acquired lymphangioma) – due to scarring processes such as recurrent infections, radiotherapy, scrofuloderma, scleroderma, keloids, tumors, tuberculosis, repeated trauma BJD 132:1014–1016, 1996 Lymphangioma circumscriptum JAAD 55:S106–107, 2006; J Derm Surg Oncol 14:357–364, 1988

Graft vs. host disease Pemphigus vegetans AD 128:397–402, 1992; AD 121:271–272, 1985; pemphigus vegetans, Neumann variant – cobblestoned lips, palate, and tongue JAAD 39:872–875, 1998; cerebriform tongue BJD 104:587–591, 1981 Systemic lupus erythematosus; familial lupus erythematosus – personal observation

CONGENITAL LESIONS Fetal hydantoin syndrome – personal observation

DRUGS Corticosteroid atrophy Cyclosporine – gingival hyperplasia Palifermin – personal observation Tacrolimus – gingival and tongue cobblestoning; personal observation

EXOGENOUS AGENTS Aquagenic wrinkling of palms Ped Derm 29:237–242, 2012

Lymphangioma scroti – cobblestoned, furrowed Ped Derm 24:654–656, 2007

Bromides – verrucous or vegetative lesions

Lymphatic malformation, microcystic of scrotum JAMADerm 153:103–105, 2017

Iodides – verrucous or vegetative lesions

Lymphedema, congenital, praecox – personal observation Phymatous transformation of facial cutaneous vascular malformations JAMA Derm 149:368–369, 2013

Dentures – verrucous or vegetative lesions Silica granuloma (white cobblestoned) AD 127:692–694, 1991

228 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFECTIONS AND INFESTATIONS Bartonellosis – verrucous and/or vegetative lesions

Verruciform (verrucous) xanthoma – gingiva and alveolar ridge are most common locations JAAD 42:343–347, 2000; Cutis 51:369– 372, 1993

Bejel (endemic syphilis) – verrucous or vegetative lesions

Xanthoma disseminatum JAAD 26:433–436, 1991

Calymmatobacterium granulomatis (Donovanosis) J Clin Inf Dis 25:24–32, 1997 Candidiasis – chronic nodular candidiasis; papillary hyperplasia of the palate; chronic mucocutaneous candidiasis Ann Rev Med 32:491–497, 1981; atrophic candidiasis; cobblestoning of lips Coccidioidomycosis – verrucous or vegetative lesions Condyloma acuminata Focal epithelial hyperplasia (Heck’s disease) – lips and/or palatal cobblestoning ; multiple pink lip, gingival and buccal mucosal papules; tongue papule; cobblestoned appearance; common in native Americans and Eskimo populations; HPV-13,14,32,55; Ped Derm 28:457–458, 2011; Ped Derm 26:465–468, 2009; Ped Derm 26:87–89, 2009; Cutis 77:233–234, 2006; AD 140:1227–1231, 2004; AD 138:1309–1314, 2002; BJD 144:1067–1069, 2001; Ped Derm 10:240–244, 1993; AD 127:887–892, 1991; JAAD 1:499–502, 1979 Granuloma inguinale Herpes simplex – herpetic gingivostomatitis; herpetic geometric glossitis – personal observation Histoplasmosis Cutis 55:104–106, 1995 Koplik’s spots – measles, Parvovirus B19 Leishmaniasis, mucocutaneous Leprosy Mucormycosis

INFLAMMATORY DISEASES Cheilitis granulomatosa – cobblestoned lips Crohn’s disease – – palatal or intraoral cobblestoning or granular appearance JAAD 77:795–806, 2017; JAAD 68:189–209, 2013; AD 135:439–442, 1999; nodules of gingiva JAAD 36:697–704, 1997; AD 127:887–892, 1991, JAAD 12:260–268, 1985; JAAD 27:40, 1990; cobblestoned lips Desquamative gingivitis Eruptive lingual papillitis – tongue papules composed of fungiform papillae of tip and side of tongue BJD 150:299–303, 2004 Granular appearance JAAD 27:40, 1990 Migratory mucositis of the lip Orofacial granulomatosis – facial edema with swelling of lips, cheeks, eyelids, forehead, mucosal tags, mucosal cobblestoning, gingivitis, oral aphthae BJD 143:1119–1121, 2000; in pediatric liver transplant patients Oral Dis 20:e97–102, 2014 Pyostomatitis vegetans – deep fissures, pustules, papillary projections Oral Surg Oral Med Oral Pathol 75:220–224, 1993; J Oral Pathol Med 21:128–133, 1992; Gastroenterology 103:668–674, 1992; JAAD 21:381–387, 1989; AD 121:94–98, 1985; lip ulcers; lip swelling with cobblestoning, micropustules NEJM 368:1918, 2013; cobblestoning of soft palate BJD 172L811–813, 2015

Mycobacterium tuberculosis – lupus vulgaris Dermatol Clin 26:285–294, 2008; Ped Derm 20:429–431, 2003; tuberculosis verrucosa cutis

Sarcoidosis – red pebbled, mamillated gingival (“strawberry gums”) JAAD 59:S118–120, 2008

North American blastomycosis

Whipple’s disease

Verrucous hyperplasia of the mucosa

Oral hairy leukoplakia (tongue) Paracoccidioidomycosis (palate) Dermatol Clin 26:257–269, 2008; Cutis 40:214–216, 1987

METABOLIC DISEASES

Pinta – verrucous or vegetative lesions

Pernicious anemia – cobblestoned deep red tongue

Rhinoscleroma – verrucous or vegetative lesions

Plane xanthomas

Rhinosporidiosis

Pregnancy gingivitis

Streptococcal gingivostomatitis Syphilis – chancre (primary) – verrucous or vegetative lesion; mucous patch, hyperplastic syphilis, interstitial glossitis (tertiary lues); syphilitic oral condylomata JAAD 29:756, 1993; cobblestoning of lips

NEOPLASTIC DISEASE

Verrucae vulgaris – of lips

Basal cell carcinoma

Yaws – verrucous or vegetative lesions

Bowen’s disease

Acquired dyskeratotic leukoplakia AD 124:117–120, 1988 Adenoid cystic carcinoma

Epithelioma – verrucous or vegetative lesion

INFILTRATIVE DISEASES Amyloidosis Infantile systemic hyalinosis – gingival thickening Juvenile hyaline fibromatosis (infantile systemic hyalinosis) Ped Derm 23:458–464, 2006 Lichen myxedematosus Plasma cell orificial mucositis (lips and tongue) AD 122:1321–1324, 1986

Erythroplasia of Queyrat Fordyce spots Hereditary benign intraepithelial dyskeratosis Kaposi’s sarcoma Dermatol Clin 24:509–520, 2006 Leukemia – acute myelomonocytic leukemia; erythroleukemia Lymphoma – cutaneous T cell lymphoma (CTCL) JAAD 22:569– 577, 1990; Hodgkin’s disease Melanocytic nevi

Cobblestone Appearance of the Oral Mucosa 229 Mucosal neuroma Plasmacytoma – cobblestoning of lips Plasmoacanthoma – cobblestoning of lips Proliferative verrucous hyperplasia (leukoplakia) AD 127:887–892, 1991 Sebaceous adenoma Seborrheic keratosis Squamous cell carcinoma Sublingual keratosis (leukoplakia) Verrucous carcinoma (oral florid papillomatosis) JAAD 32:1–21, 1995; AD 127:887–892, 1991 Verrucous leukoplakia – verrucous lesion

Cowden’s syndrome (multiple hamartoma syndrome) – verrucous and papillomatous lesions on labial and buccal mucosa, fauces, and oropharynx; palatal cobblestoning JAAD 77:809–830, 2017; JAAD 11:1127–1141, 1984; Ann DV 106:453–463, 1979; AD 114:743– 746, 1978; Ann Intern Med 58:136–142, 1963; lingual cobblestoning AD 146:337–342, 2010; smooth pink or whitish papules of palatal, gingival, and labial mucosa Oral Surg 49:314–316, 1980; oral cobblestoning An Bras Dermatol 88 (suppl 1):52–55, 2013 Dermochondrocorneal dystrophy AD 124:424–428, 1988 Down’s syndrome – personal observation Dyskeratosis congenita Epidermal nevus syndrome Syndromes of the Head and Neck, p. 363, 1990; Oral Surg Oral Med Oral Pathol 20:201–212, 1965

White sponge nevus JAAD 77:809–830, 2017; AD 117:73–76, 1981

Goltz’s syndrome- personal observation

PARANEOPLASTIC DISEASES

Melkersson-Rosenthal syndrome

Acanthosis nigricans, malignant Cutis 89:14–16, 2012; JAAD 25:361–365, 1991; lips and/or palatal cobblestoning JAMADerm 151:1381–1383, 2015; AD 130:649–654, 1994; JAAD 31:1–19, 1994; Clin Genet 50:160, 1991; malignant acanthosis nigricans and tripe palms; cobblestoned lips, buccal mucosa, and tongue – pancreatic carcinoma Cutis 78:37–40, 2006

Multicentric reticulohistiocytosis – digital papule; knuckle pads, yellow papules and plaques AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968

PRIMARY CUTANEOUS DISEASES Black hairy tongue – verrucous or vegetative changes Cheilitis glandularis Coated tongue – personal observation Darier’s disease (keratosis follicularis) JAAD 77:809–830, 2017; Clin Dermatol 19:193–205, 1994; JAAD 27:40–50, 1992; JAAD 27:40–50, 1992 Diffuse epithelial hyperplasia Fissured tongue Geographic stomatitis J Oral Pathol Med 20:425–428, 1991 Geographic tongue (normal variant, psoriasis, pustular psoriasis, Reiter’s syndrome) J Oral Pathol Med 20:425–428, 1991

Lipoid proteinosis JAAD 77:809–830, 2017; JAAD 39:149–171, 1998

Multiple endocrine neoplasia syndrome (MEN I) – gingival cobblestoning AD 133:853–857, 1997; angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia; mutation in menin, a nuclear protein involved in cell cycle regulation and proliferation JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004 Multiple mucosal neuroma syndrome – MEN Type II (palate) Neurofibromatosis – papillomatosis of the palate Nevus sebaceous syndrome (Schimmelpenning-Feuerstein-Mims syndrome) – cobblestoning of hard palate JAAD 52:S62–64, 2005; Am J Dis Child 104:675–679, 1962; Fortschr Roentgenstr 87:716– 720, 1957 Pachyonychia congenita

Hypertrophy of fungiform papillae of tongue

Pseudoxanthoma elasticum JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; AD 124:1559, 1988

Lichen planus; lichen planus vegetans

Reactive arthritis syndrome

Scrotal tongue

Sjogren’s syndrome

Transient papillitis of the tongue – personal observation

Sweet’s syndrome Tuberous sclerosis – gingival fibromas

PSYCHOCUTANEOUS DISEASES Factitial cheilitis – cobblestoned lips Ped Derm 16:12–15, 1999

SYNDROMES Bannayan-Riley-Ruvalcaba syndrome AD 132:1214–1218, 1996 Birt Hogg-Dube syndrome – fibrofolliculomas AD 135:1195–1202, 1999 Costello syndrome – linear papillomatous papules of upper lip; HRASopathy; loose redundant palmoplantar skin, sparse curly hair, palmoplantar keratosis and deep creases of hands and feet; nail dystrophy, long eyelashes BJD 168:903–904, 2013

Xerostomia – tongue cobblestoning

TOXINS Nicotine stomatitis Tobacco chewing – diffuse epithelial hyperplasia

TRAUMA Morsicatio buccarum (cheek biting) – oral papillomatosis due to chronic buccal trauma Cutis 43:254–257, 1989; cobblestoning with biting papillomas Dentate tongue – scalloping

230 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Papillary hyperplasia of the palate

VASCULAR Lymphangioma circumscriptum Otolaryngol Head Neck Surg 90:283, 1982

Oral bullae J Acquir Immune Defic Syndr Hum Retroviral 13:87–92, 1996 Palatal perforation Otolaryngol Head Neck Surg 116:565–566, 1997 Palpable purpura (leukocytoclastic vasculitis) Neurol Clin 15:945– 957, 1997 Pott puffy tumor Rev Infect Dis 13:606–608, 1991

Lymphatic malformation BJD 148:1279–1282, 2003

Pseudovasculitis Mayo Clin Proc 80:671–673, 2005

Pyogenic granuloma – verrucous or vegetative lesion

Pyoderma gangrenosum Clin Exp Dermatol 38:878–882, 2013

Granulomatosis with polyangiitis (gingival hyperplasia) – strawberry gingiva AD 130:861–867, 1994; JAMA 246:2610, 1981

Raynaud’s phenomenon Clin Rheumatol 21:343–344, 2002; Eur Respir J 9:175–177, 1996 Red nodules JAAD 21:570–572, 2989

 OCAINE USE, CUTANEOUS C MANIFESTATIONS (COKE, SNOW, FLAKE, BLOW) Acute generalized exanthematous pustulosis (AGEP) AD 143:430– 431, 2007 Acute multifocal skin necrosis Acta DV 76:239–241, 1996 Angioedema Ann Emerg Med 34:296–297, 1999 Buerger’s disease Arch Intern Med 161:486, 2001; Arch Intern Med 160:2057–2060, 2000

Scleroderma BJD 150:1–10, 2004; South Med J 91:961–963, 1998; South Med J 82:1275–1276, 1989 Stevens-Johnson syndrome (erythema multiforme major) Dermatology 201:258–260, 2000 Subcutaneous fat necrosis of the newborn Clin Pediatr (Phila) 33:317–318, 1994 Urticaria Ann Emerg Med 34:296–297, 1999 Urticarial vasculitis; urticaria and urticarial vasculitis Clin Exp Dermatol 45:630–632, 2020; BJD 141:600–601, 1999 Warts – nasal (snorter)warts; transmission of HPV on dollar bills

Cocaine bugs – delusions of parasitosis; formication Am J Addiction 21:180–181, 2012; Cutis 42:273–274, 1988

CONCENTRIC LESIONS

Cocaine-related bullous disease JAAD 12:585–586, 1985

Acute hemorrhagic edema of infancy

Crack hands – blackened hyperkeratotic palms; palmar and digital hyperkeratosis Cutis 50:193–194, 1992 Chronic skin ulcers Ann Plast Surg 24:268–270, 1990 Cocaine-induced midline destructive lesions (CIMDL) – intranasal injection of crack cocaine; Raynaud’s phenomenon, distal ulcers, digital gangrene, Buerge-like diseases, scars, necrotizing panniculitis, granulomas, puffy hands J Eur Acad Dermatol Venereol 32:1420–1426, 2018; midline destructive granulomas – nasal septal perforation; palatal perforation, madarosis NEJM 314:1324, 1986; Eur Arch Otorhinolaryngol 255:446–447, 1998; JAAD 32:286–287, 1995; J Rheumatol 17:838–840, 1990; Arch Otolaryngol Head Neck Surg 114:90–91, 1988 Cutaneous fibrosis AD 18:1647, 1992 Dental caries Int Dent J 55:365–369, 2005 Digital necrosis BJD 150:1–10, 2004; Ann Int Med 133:923–924, 2000 Eosinophilic granulomatosis with polyangiitis Eur Respir J 9:175– 177, 1996 Gingival recession J Periodontol 68:485–488, 1997 Henoch-Schonlein purpura Neurol Clin 15:945–957, 1997 Levamisole contaminated cocaine – acral intravascular thrombotic vasculopathy; atypical ANCA+; acral necrosis Clin Inf Dis 18:40–49, 2015 Lip smacking – cuts and burns on lips Nasal septal perforation Int Dent J 55:365–369, 2005; Br Dent J 198:333–334, 2005 Necrotizing granulomatous vasculitis J Rheumatol 29:1795–1797, 2002 Necrotizing ulcers Acta DV 76:239–241, 1996 Necrotizing vasculitis Neurol Clin 15:945–957, 1997

Bullous pemphigoid – personal observation Cryotherapy of wart – personal observation Equestrian perniosis – annular, arcuate, concentric purpuric plaques of lateral thighs JAMADerm 153:83–84, 2017 Erythema gyratum repens Erythema multiforme JAMADerm 155:108, 2019 Henoch-Schonlein purpura Interferon – erythema gyratum repens due to pegylated interferon AD 148:1213–1214, 2012 Leprosy – personal observation Lupus erythematosus – subacute cutaneous lupus erythematosus Cutis 93:177,183–184, 2014; Ann DV 128:244–246, 2001 Lyme disease – erythema chronicum migrans Cutaneous T-cell lymphoma – personal observation Metastatic breast cancer AD 126:649–652, 1990 Pemphigoid gestations – concentric bullae JAMADerm 150:445– 446, 2014 Pemphigus herpetiformis – concentric targetoid lesions; herpetiform lesions; serpiginous blisters Ped Derm 30:760–762, 2013 Psoriasis – koebnerization of psoriasis under colostomy bag JAMADerm 156:805, 2020; Int J Dermatol 39:695–697, 2000 Bullous pyoderma gangrenosum – associated with myeloproliferative disorders Sarcoid – personal observation Tinea corporis, treated with topical corticosteroids; generalized dermatophytosis – personal observation; Trichophyton rubrum J Cut Med Surg 10:52–56, 2006; Microsporum gypseum Mycoses 49:150–151, 2006 Tinea imbricata (Trichophyton concentricum) Ped Derm 33:253– 263, 2016

CUTANEOUS HORNS

CONJUNCTIVAL LESIONS, PIGMENTED

231

WHITE PIGMENTATION Band keratopathy Nephrogenic systemic fibrosis

JAAD 38:971–978, 1998

NON-MELANOCYTIC Brown pigmentation   Argyria, localized Dermatol Online J 11:12, 2005   Cicatricial pemphigoid with symblepharon   Lupus erythematosus – nodular episcleritis   Gaucher’s disease  Jaundice  Adrenochrome deposits – due to topical epinephrine – flecks of pigmentation in caruncle and plica  Silver  Mascara  Ochronosis  Phakomatosis pigmentokeratotica – organoid nevus and nevus spilus SkinMed 11:125–128, 2013  Quinine  Iron  Hemosiderin   Wilson’s disease  Xanthoma disseminatum JAAD 56:302–316, 2007 Red papule  Conjunctival papilloma – red papule of bulbar conjunctivum Cutis 89:38–40, 2012 Yellow papules   Lupus erythematosus – episcleritis Dendritic melanocytic lesions  Benign epithelial melanosis (congenital melanosis; racial variant)  Secondary acquired melanosis – associated with inflammatory conditions, scar tissue, and conjunctival tumors  Primary acquired melanosis – with or without atypia; may be pre-malignant Fusiform melanocytic lesions  Nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris) BJD 67:317–319, 1955   Pigmented episcleral spot (Axenfeld’s nerve loop) LEOPARD syndrome JAAD 50:S70–74, 2004 Melanoma Nevomelanocytic proliferation   Blue nevi of sclerae or conjunctivum AD 139:1209–1214, 2003  Melanocytic nevi (conjunctival nevi) – brown periphery, blue center   Nevus of Ota   Spitz nevus Pigmented spindle cell tumor of the limbus Farber’s disease (lipogranulomatosis) – lysosomal acid ceramidase deficiency (N-acylsphingosine amidohydrolase) (chromosome 8p22-21.2); deformed or stiff joints with painful limb contractures and red periarticular subcutaneous nodules (proximal and distal interphalangeal joints, wrist, elbow, knees, ankles, metatarsals), and progressive hoarseness; rarely nodules seen in conjunctivae, nostrils, ears, mouth; heart, liver, spleen, lung; progressive psychomotor retardation Ped Derm 26:44–46, 2009; Eur J Ped 157:515–516, 1998; AD 130:1350–1354, 1994

CRANIOSYNOSTOSIS Apert’s syndrome – acneiform lesions Beare-Stevenson syndrome – cutis verticis gyrate Curry-Jones syndrome – linear hypo- or hyperpigmented lesions, palmoplantar pitting, streaks of atrophy, hypertrichosis, trichoblastoma and nevus sebaceous, polydactyly or preaxial polysyndactyly, dysmorphic facies, macrocephaly, microcephaly, dental anomalies, craniosynostosis, anal stenosis, myofibromas and smooth muscle hamartomas, medulloblastomas, cerebral malformations(agenesis of corpus callosum), developmental delay, cataracts, microphthalmia, coloboma, glaucoma, cryptorchidism; mutation in SMOc.1234C>T BJD 182:212–217, 2020; Clin Dysmorphol 4:116–129, 1995 Craniosynostosis, anal anomalies, and porokeratosis (CAP/ CDAGS) – autosomal recessive; craniosynostosis, clavicular hypoplasia, delayed fontanel closure, cranial defects (parietal foramina), deafness, imperforate anus or anterior placement of anus, genitourinary abnormalities (hypospadias and urethrorectal fistula), and skin eruption (porokeratosis-­like lesions), mental retardation, scant hair, Staphylococcus aureus infections JAAD 68:881–884, 2013; Am J Hum Genet 77:161–168, 2005; J Med Genet 35:763–766, 1998 Crouzon syndrome Jason-Weiss syndrome – limb abnormalities Mlonke syndrome – limb abnormalities Pfeiffer syndrome – limb abnormalities Saethre-Chotzen – craniosynostosis and hand abnormalities

CUTANEOUS HORNS Cutis 64:111–112, 1999

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSFUNCTION Chronic mucocutaneous candidiasis An Bras Dermatol 89:641–644, 2014 Lupus erythematosus AD 121:837–838, 1985; discoid lupus erythematosus BMJ Case Rep April 3, 2014; Indian J DV Leprol 80:461–462, 2014 Trichodysplasia of immunosuppression (trichodysplasia spinulosa, polyoma virus-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy) AD 142:1643– 1648, 2006; JAAD 52:540–541, 2005

CONGENITAL LESIONS Congenital ectopic nail – cutaneous horn of fingertip Ped Derm 30:267–269, 2013; congenital palmar nail syndrome, Pierre-Robin

232

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

syndrome, ectodermal dysplasia, polydactyly, congenital onychodysplasia Congenital trichoid keratosis – cutaneous horns on scalp AD 128:1549–15550, 1992

INFECTIONS AND INFESTATIONS

Kaposi’s sarcoma Int J Dermatol 53:e65–67, 2014; JAAD 64:447– 448, 2011; Cutis 64:111–112, 1999; Cutis 31:610–612, 1983; AD 98:37–40, 1968 Keratoacanthoma Ann Dermatol 23:89–91, 2011; Cutis 64:111– 112, 1999; AD 120:736–740, 1984 Lentigo maligna melanoma Dermatol Surg 36:1759–1762, 2010 Melanocytic nevus – intradermal nevus BJD 124:449–452, 1991

Dermatophytes – hyperkeratosis with cutaneous horns Ann DV 125:705–707, 1998

Melanoma Am J Dermatopathol 40:869–871, 2018; Dermatol Reports 5:e3, 2013

Histoplasmosis – transepidermal elimination of histoplasmosis in AIDS Cutis 47:397–400, 1991

Merkel cell carcinoma Dermatol Pract Concept 5:47–50, 2015

Leishmaniasis AD 123:168–169, 1987 Molluscum contagiosum Ann Dermatol 23:262–263, 2011; JAAD 43:409–432, 2000 Rhinosporidiosis Indian Dermatol Online J 10:178–179, 2019 Verruca vulgaris Cutis 80:145–148, 2007; Cutis 64:111–112, 1999; giant disseminated verrucosis (HPV2) (giant verrucous claw hands and feet) associated with idiopathic CD4 lymphopenia AD 146:69– 73, 2010

Metastases –renal cell carcinoma BMJ Case Rep Aug 18, 2017; Cutis 64:111–112, 1999; cutaneous horn of forehead J Derm Surg Oncol 8:815, 1983 Multiple myeloma – follicular spicules Dermatol Online J Oct 15, 2019 Nevus corniculatus – filiform keratoses, cutaneous horns, and giant comedones BJD 122:107–112, 1990 Nevus sebaceus of Jadassohn Organoid nevus Paget’s disease of the nipple J Surg Oncol 29:237–239, 1985

INFILTRATIVE DISORDERS Juvenile xanthogranuloma – finger-like pedunculated papule Clin Case Rep 8:65–67, 2019; Ann Dermatol 28:783–784, 2016; J Clin Diagn Res 9:PD13–14, 2015; Ped Derm 30:261–262, 2013; Ped Derm 24:576–577, 2007

INFLAMMATORY DISORDERS Keratotic and micaceous pseudoepitheliomatous balanitis Pseudoepitheliomatous keratotic and micaceous balanitis Indian J DV Leprol 76:547–549, 2010

Pilar cyst Pilomatrixoma J Cutan Pathol 46:801–804, 2019; Cutis 69:23–24, 2002 Porokeratosis, giant Indian J DV Leprol 83:66–67, 2017 Sebaceous adenoma Cutis 64:111–112, 1999; J Cutan Pathol 22:185–187, 1995; J Cutan Pathol 11:396–414, 1984 Sebaceous carcinoma Br J Ophthalmol 95:1470, 1478, 2011; Br J Ophthalmol 82:1049–1055, 1998; Br J Plast Surg 48:93–96, 1995; JAAD 25:685–690, 1991; J Derm Surg Oncol 11:260–264, 1985; Cutis 31:610–612, 1983 Seborrheic keratosis Am J Ophthalmol Case Rep 4:64–66, 2016

Sarcoidosis Cutis 104:e28–29, 2019

Squamous cell carcinoma Yonago Acta Med 61:140–141, 2018; Arch Craniofac Surg 17:25–27, 2016; BJD 164:973–979, 2011; Cutis 64:111–112, 1999; in scar BJD 164:673–675, 2011

METABOLIC DISORDERS

Syringocystadenoma papilliferum BJD 142:1242–1244, 2000

Calcinosis cutis –subepidermal calcified nodule (Winer’s nodular calcinosis); at base of entrance of external auditory canal; Ped Derm 35:515–516, 2018; Ped Derm 25:253–254, 2008

Trichilemmal carcinoma Ann Saudi Med 32:1–2, 2012; BJD 143:646–647, 2000 Trichilemmal cyst with horn Trichilemmal horn JAAD 39:368–371, 1998; BJD 100:303–309, 1979

NEOPLASTIC DISORDERS

Trichilemmoma – personal observation

Acquired digital fibrokeratoma – personal observation

Trichofolliculoma Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.67

Actinic keratosis Cutis 64:111–112, 1999; JAAD 37:392–394, 1997 Adenoacanthoma Cutis 64:111–112, 1999 Basal cell carcinoma Cutis 64:111–112, 1999; pseudohorn Cutis 48:379, 1991 Benign lichenoid keratosis

Verrucous acanthoma Verrucous carcinoma, including epithelioma cuniculatum J Clin Diagn Res 11:2004–2005, 2017 Warty dyskeratoma Am J Dermatopathol 37:802–804, 2015

Bowen’s disease Cutis 64:111–112, 1999 Dermatofibroma Epidermal inclusion cyst Epidermal nevus Ped Derm 34:e290–291, 2017 Epidermolytic acanthoma Fibroma

PRIMARY CUTANEOUS DISEASES Darier’s disease, cornifying AD 112:495–503, 1976 Ectopic nail JAAD 10:114–116, 1984; post-traumatic ectopic nail JAAD 50:323–324, 2004; ectopic nail with polydactyly JAAD 53:1092–1093, 2005

Giant cutaneous horns J Drugs Dermatol 18:697–698, 2019; Ann Plast Surg 43:674, 1999

Hypertrophic lichen planus BJD 144:424–425, 2001

Granular cell tumor

Palmoplantar keratoderma with cutaneous horns Int J Dermatol 31:369–370, 1992

Inverted follicular keratosis

Lichen simplex chronicus – personal observation

Cutis Laxa-Like Appearance 233 Penile horn JAAD 75:E127–128, 2016; Urology 85:e45, 2015; Urology 30:156–158, 1987; JAAD 13:369–373, 1985; J Urol 132:1192–1193, 1984

DEGENERATIVE DISORDERS Aging

Pityriasis rubra pilaris – spiny hyperkeratoses Prurigo nodularis Acta DV (Stockh)76:85–86, 1996 Psoriasis JAAD 5:681–683, 1981

DRUG-INDUCED Hypersensitivity reaction AD 123:1211–1216, 1987 Isoniazid (INH) – acquired cutis laxa JAAD 46:128–130, 2002

SYNDROMES Buschke-Fischer-Brauer keratoderma (punctate palmoplantar keratoderma) (keratodermia palmo-plantaris papulosa) (keratodermia palmoplantare papuloverrucoides progressiva) Clin Cases Dermatol 4:27, 1992 Focal palmoplantar and oral mucosa (gingival) hyperkeratosis syndrome (MIM:148730) – palmoplantar keratoderma, leukoplakia, and cutaneous horn of the lips BJD 146:680–683, 2002

Minocycline-induced generalized postinflammatory elastolysis Am J Med 109:340–341, 2000 Penicillamine Dermatol Online J May 15, 2016; Cutis 76:49–53, 2005; BJD 142:560–561, 2000; Isr J Med Sci 30:667–669, 1994; Lancet ii:858, 1983 Penicillin allergy – acquired cutis laxa JAAD 46:128–130, 2002; Am J Dermatopathol 5:267–276, 1983

EXOGENOUS AGENTS TOXINS

Leeches applied to skin – anetoderma Int J Derm 35:226–227, 1996

Arsenical keratosis Cutis 64:111–112, 1999

Saltpetre-induced atrophy

TRAUMA

INFECTIONS

Burn scar J Burn Care Res 39:168–170, 2018

Cutaneous Lyme Borreliosis – acrodermatitis chronica atrophicans, cutis laxa-like changes, red patches, erythema migrans, erythema and edema of foot, poikilodermatous changes, red macules and telangiectasias JAAD 72:683–689, 2015

VASCULAR DISORDERS Angiokeratomas J Dermatol 46:e388–390, 2019; solitary angiokeratoma Indian J Dermatol 61:236, 2016; Int J Dermatol 51:313–315, 2012 Angiokeratoma circumscriptum J Dermatol 44:e192–193, 2017 Angioma Pyogenic granuloma Indian Dermatol Online J 7:114–116, 2016; Cutis 31:610–612, 1983

CUTIS LAXA-LIKE APPEARANCE  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Complement deficiency Lancet ii:858, 1983 Cutis laxa with hypocomplementemia and nephrotic syndrome AD 123:1211–1216, 1987 Dermatitis herpetiformis BJD 135:130–134, 1996; JAAD 29:846– 848 1993 Lupus erythematosus – systemic LE JAAD 8:869, 1983; lupus panniculitis (lupus profundus) – thighs, buttocks, arms, breasts, face Ann DV 117:841–844, 1990; urticarial vasculitis Am J Dermatopathol 40:433–437, 2018 Rheumatoid arthritis – acral cutis laxa JAAD 46:128–130, 2002 Urticaria – acquired cutis laxa JAAD 46:128–130, 2002; chronic urticaria JAAD 33:896–899, 1995

Leprosy – blepharochalasis Clinics in Dermatol 33:8–18, 2015 Onchocerciasis – "hanging groin" due to destruction of elastic fibers; redundant stretched abdominal skin JAAD 73:929–944, 2015; Cutis 65:293–297, 2000 Syphilis – localized cutis laxa JAAD 46:128–130, 2002

INFILTRATIVE DISEASES Amyloidosis – acral elastolytic lesions of myeloma-associated amyloidosis of fingertips JAAD 58:S32–33, 2008; Australasian J Dermatol 43:144–146, 2002; AD 126:657–660, 1990; Clin Exp Dermatol 11:87–91, 1986; acrolocalized acquired cutis laxa; depressed fingertip AD 146:1433–1434, 2010; ptosis and dermatochalasis in primary systemic amyloidosis Ophthalmic Surg 18:495– 497, 1987; hemodialysis-­associated beta-2 microglobulin amyloidosis BJD 152:250–257, 2005; cutis laxa JAMADerm 150:1357–1358, 2014; AD 147:323–328, 2011; Cutis 69:114–118, 2002 Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100; xanthoma and xanthelasma-­like lesions (red-brown-yellow papules and plaques); flat wart-like papules of face; lesions occur in folds; skin becomes slack with atrophy of folds and face; also lesions of eyelids, axillae, groin, neck; bony lesions; diabetes insipidus, painless exophthalmos, retroperitoneal, renal, and pulmonary histiocytic infiltration JAAD 57:1031–1045, 2007; AD 143:952–953, 2007; Hautarzt 52:510–517, 2001; Medicine (Baltimore) 75:157– 169, 1996; Virchow Arch Pathol Anat 279:541–542, 1930

INFLAMMATORY DISEASES CONGENITAL LESIONS

Amyotrophic lateral sclerosis JAAD 17:1006–1012, 1987

Congenital cutis laxa Indian Pediatr 49:771, 2012; AD 92:373, 1965

Angioedema

234 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Aortitis – acquired cutis laxa Pediatr Pathol 1:199–210, 1983

PHOTODERMATOSES

Erythema multiforme – acquired cutis laxa JAAD 46:128–130, 2002

Severe actinic damage (dermatoheliosis)

Post-inflammatory cutis laxa Sarcoid – localized cutis laxa JAAD 46:128–130, 2002

METABOLIC DISEASES

PRIMARY CUTANEOUS DISEASES Acanthosis nigricans, generalized – periflexural laxity Ped Derm 18:213–216, 2001

Celiac disease – acquired cutis laxa JAAD 46:128–130, 2002; BJD 135:130–134, 1996

Acral localized acquired cutis laxa BJD 134:973–976, 1996;

Congenital hemolytic anemia

Anetoderma AD 120:1032–1939, 1984

Gangliosidosis – X-linked; gingival hypertrophy, macroglossia, coarse facies, micrognathia, loose skin, inguinal hernia, delayed growth, hepatosplenomegaly, neonatal hypotonia, delayed motor development Ped Derm 18:534–536, 2001

Blepharochalasis (Fuchs syndrome) Hautarzt 29:474–477, 1978

Lysyl oxidase deficiency Clin Genet 51:109–114, 1997 Marasmus – severe protein and caloric deprivation; wrinkled, loose, redundant dry skin; extensive loss of subcutaneous fat JAAD 21:1–30, 1989 Mucopolysaccharidosis Type III (Sanfilippo syndrome) – skin thickened and loose Mucopolysaccharidosis Type VII (Sly syndrome) – skin laxity Necrobiosis lipoidica diabeticorum – localized cutis laxa JAAD 46:128–130, 2002 Nephrogenic systemic fibrosis; anetoderma – personal observation Nephrotic syndrome – acquired cutis laxa JAAD 46:128–130, 2002; AD 123:1211–1216, 1987 Weight loss – cutaneous laxity due to marked weight loss; wasting syndrome

NEOPLASTIC DISEASES Generalized smooth muscle hamartomas with skin folding Granulomatous slack skin syndrome – CD30+ T-cell lymphoproliferative disorder BJD 147:998–1002, 2002; TCR-gamma BJD 157:405–407, 2007 Heavy chain deposition disease – acquired cutis laxa JAMADerm 150:1192–1196, 2014; JAAD 59:S99–101, 2008 Lymphoma – cutaneous angiocentric T-cell lymphoma – acquired cutis laxa Int J Dermatol 36:772–776, 1997; lymphoplasmacytoid lymphoma AD 131:110–111, 1995; cutaneous T-cell lymphoma (CTCL) – granulomatous slack skin – lax skin masses JAAD 70:205–220, 2014; AD 144:1609–1617, 2008; AD 141:1595–1600, 2005; JAAD 51:165–185, 2004; JAAD 46:325–357, 2002; BJD 142:353–357, 2000; Ped Derm 14:204–208, 1997; JID 89:183, 1987; AD 121:250–252, 1985 Myeloma – acquired cutis laxa JAAD 46:128–130, 2002; Cutis 57:267–270, 1996; BJD 110:363–367, 1984; Cutis 26:209–211, 1980; AD 112:853–855, 1976; acral acquired cutis laxa Cutis 69:114–118, 2002; JAAD 21:33–40, 1989; AD 112:853–855, 1976; IgA myeloma JAAD 60:1052–1057, 2009 Neurofibroma – localized cutis laxa JAAD 46:128–130, 2002

JAAD 21:33–40, 1989

Cutis laxa Ped Derm 19:412–414, 2002; JAAD 29:846–848, 1993, Ped Derm 2:282–288, 1985  Inherited (dermatochalasis connata) – mutations in ELN1 (encoding elastin), FBLN5 (encoding fibulin-5), and FBLN4 (encoding fibulin-4)  Autosomal dominant – large earlobes, beaked nose; mutation in elastin gene Ped Derm 31:347–349, 2014; JAAD 66:842–851, 2012; AD 140:1135–1139, 2004; Ped Derm 21:167–170, 2004; Clin Genet 39:321–329, 1991  Autosomal recessive – Types I (FBLN4), IIA (ATP6VOA2), IIB, III (PYCR1); diaphragmatic hernia, GI and GU diverticulae, pulmonary emphysema, cardiac abnormalities Ped Der 21:167– 170, 2004  X-linked dominant (occipital horn syndrome (formerly Ehlers-Danlos syndrome type IX)/ Menkes’ disease Cutis laxa – X-linked recessive (occipital horn syndrome; formerly Ehlers-Danlos type IX) – occipital exostoses; pili torti; lysyl oxidase deficiency, skeletal dysplasias, joint hypermobility, chronic diarrhea, obstructive uropathy Ped Derm 31:347–349, 2014; Ped Derm 21:167–170, 2004; Clin Dysmorphol 8:179–183, 1999 Transient neonatal cutis laxa   Neonatal cutis laxa with Marfan phenotype   Acquired-Associated with:    Type 1 – generalized acquired elastolysis    Complement deficiency AD 123:1211–1216, 1987    Drug hypersensitivity    Heavy chain deposition disease – monoclonal gammopathy JAAD 79:945–947, 2018; JAAD 59:S99–101, 2008    Inflammatory skin disease    Klippel-Trenaunay-Weber syndrome    Lymphoma – angiocentric T-cell lymphoma Int J Dermatol 36:764–768, 1997    Malignancy     Multiple myeloma Eur J Dermatol 127:654–655, 2017; Cutis 57:267–270, 1996; Am J Dermatopathol 18:533–537, 1996    Penicillamine dermatopathy AD 125:92–97, 1989    Sarcoid JAAD 29:846–848, 1993    Systemic lupus erythematosus    Syphilis   Type 2 – Marshall’s syndrome – Sweet’s syndrome followed by cutis laxa J Cut Pathol Aug 22, 2019; JAAD 66:842–851, 2012; Ped Derm 26:452–457, 358–360, 2009; AD 131:1175–1177, 1995    Acrolocalized acquired cutis laxa – face with linear furrows, palms, and soles BJD 176:832–835, 2017; Ped Derm 28:421–423, 2011; BJD 134:973–976, 1996; JAAD 21:33–40, 1989;

PARANEOPLASTIC DISEASES

Elastoderma – localized skin laxity of the neck, trunk or arm JAAD 53:S147–149, 2005; JAAD 33:389–392, 1995

Acquired cutis laxa JAAD 77:1145–1158, 2017

Elastolysis of the earlobes JAAD 14:145–146, 1986

Plasmacytoma – nodal plasmacytoma with IgG-lambda and IgA-kappa gammopathy AD 147:328–330, 2011

Elastosis perforans serpiginosa with pseudoxanthoma elasticumlike changes in Moya-Moya disease (bilateral stenosis and

Cutis Laxa-Like Appearance 235 occlusion of basa intracranial vessels and carotid arteries) BJD 153:431–434, 2005 Lichen myxedematosus Cutis 39:219–223, 1987 Multiple benign ring-shaped skin creases Eur J Ped 138:301–3,1982 Pseudoxanthoma elasticum – linear and reticulated yellow papules and plaques; mutation in GGCX gene BJD 161:635–639, 2009; JAAD 42:324–328, 2000; JAAD 43:337–339, 2000; Dermatology 199:3–7, 1999; AD 133:664–666, 1997; AD 124:1559, 1988; acquired pseudoxanthoma elasticum – farmers exposed to saltpeter (calcium-ammonium-nitrate salts); antecubital fossa JAAD 51:1–21, 2004; Acta DV 78:153–154, 1998; Acta DV 58:319–321, 1978; periumbilical perforating pseudoxanthoma elasticum JAAD 51:1–21, 2004; JAAD 26:642–644, 1992; AD 115:300–303, 1979

SYNDROMES Ablepharon macrostomia syndrome – absent eyelids, ectropion, abnormal ears, hypertelorism, aplasia or rudimentary nipples, dry, lax, redundant skin, macrostomia, ambiguous genitalia Hum Genet 97:532–536, 1996; Am J Med Genet 31:299–304, 1988 Acrogeria of the Gottron type Eur J Dermatol 10:36–40, 2000 Alagille syndrome – cutis laxa-like changes with resolution of xanthomas after liver transplantation Ped Derm 15:199–202, 1998

ARCL1A – supravalvular aortic stenosis; lethal emphysema Ped Derm 31:347–349, 2014   ARCL1B – lethal pulmonary hypertension Ped Derm 31:347–349, 2014   ARCL1C – Urban-Rifkin-Davis syndrome – mild cardiovascular involvement Ped Derm 31:347–349, 2014   ARCL2A – growth and developmental delay; abnormal glycosylation of serum proteins Ped Derm 31:347–349, 2014   ARCL2B – growth and developmental delay; triangular face Ped Derm 31:347–349, 2014   ARCL3A – DeBarsey syndrome; growth and developmental delay, corneal clouding, athetoid movements Ped Derm 31:347–349, 2014 Cutis laxa type II – autosomal recessive; facial dysmorphism with all the changes of wrinkly skin syndrome; pre and postnatal growth retardation, delayed motor development, delayed closure of large fontanelle, congenital hip dislocation, bone dysplasias, parallel strips of redundant skin of back Ped Derm 23:225–230, 2006; Ped Derm 21:167–170, 2004 Cutis laxa type III – autosomal recessive; severe mental retardation, corneal clouding Ped Derm 21:167–170, 2004 Cutis laxa type IIIB – loose folds of wrinkled skin, progeroid facies, osteopenia, central nervous system abnormalities JAMADerm 155:257–259, 2019 Cutis laxa, congenital with ligamentous laxity, delayed development, Dandy-Walker malformation, minor heart and osseous defects Clin Genet 45:318–322, 1994

Ankyloblepharon-ectrodactyly-cleft lip/palate syndrome (AEC syndrome) – periorbital wrinkling

Cutis laxa with bone dystrophy (osteoporosis) Am J Dis Child 137:452–454, 1983

Arterial tortuosity (X-linked cutis laxa syndrome) – mutation in SLC2A10 JAAD 66:842–851, 2012; resembles Loeys-Dietz syndrome

Cutis laxa, craniofacial defects, and hypotonia J Clin Dysmorphol 1:24–25, 1983 Cutis laxa with early onset emphysema Thorax 49:836–837, 1994

Ascher syndrome Int J Derm 31:710–712, 1992

Cutis laxa, late closure of fontanels, intrauterine growth retardation, hyperlaxity of joints Pediatrics 72:850–856, 1983

Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Syndrome Ident 8:6–9, 1982 Beare-Stevenson cutis gyrata syndrome – redundant loose facial skin Cantu syndrome Cardiofaciocutaneous syndrome – shares findings of Costello syndrome such as cutis laxa, thin nails, curly hair, increased nevi, pruritus, hyperhidrosis Ped Derm 30:665–673, 2013 Chromosome 6q deletion syndrome – cutaneous and join laxity Ped Derm 11:281–282, 1994 Coffin-Lowry syndrome – X-linked inheritance; straight coarse hair, prominent forehead, prominent supraorbital ridges, hypertelorism, large nose with broad base, thick lips with mouth held open, large hands, tapering fingers, severe mental retardation; loose skin easily stretched, cutis marmorata, dependent acrocyanosis, varicose veins Clin Genet 34:230–245, 1988; Am J Dis Child 112:205–213, 1966 Costello syndrome – cutis laxa (loose thick skin) of neck, hands, and feet; papillomas around nose and mouth; acanthosis nigricans, thin nails, sparse curly hair, sparse eyebrows; increased numbers of nevi, hyperhidrosis, pruritus; deep palmoplantar creases; HRAS missense mutation Ped Derm 30:665–673, 2013; J Med Genet 31:486–489, 1994

Cutis marmorata telangiectatica congenita syndrome – body asymmetry, 2–3 toe syndactyly, hypotonia, developmental delay, midfacial vascular stains, joint laxity, loose skin Ped Derm 24:555– 556, 2007 DeBarsy syndrome (Type III) – autosomal recessive progeroid (premature aging) syndrome; lax wrinkled skin; cloudy corneas, mental retardation, pseudoathetoid movements, synophrys, pinched nose, thin skin, lack of subcutaneous tissue, sparse hair Ped Derm 19:412–414, 2002; Eur J Pediatr 144:348–354, 1985 Duplication of the eyebrows, stretchable skin and syndactyly Dwarfism-alopecia-pseudoanodontia-cutis laxa Edward’s syndrome (Trisomy 18) – cutis laxa of neck, hypertrichosis of the forehead and back, hemangiomas J Med Genet 15:48–60, 1978 Ehlers-Danlos syndrome – scarring; cutis laxa complicating Ehlers-­Danlos syndrome type II Clin Exp Derm 21(2)135–137, 1996; Ehlers-­Danlos syndrome type IX – X-linked Elejalde syndrome (acrocephalopolydactylous dysplasia) Birth Defects 13:53–67, 1977 Geroderma osteodysplastica (Bamatter syndrome) (osteodysplastic geroderma) – autosomal recessive; short stature, cutis laxa-like changes with drooping eyelids and jowls (characteristic facies with hypoplastic midface), alopecia, bone fragility with osteoporosis and skeletal abnormalities, scoliosis; lax wrinkled, atrophic skin, joint hyperextensibility, growth retardation; macrocephaly Ped Derm 23:467–472, 2006; Ped Derm 16:113–117, 1999; Am J Med Genet 3:389–395, 1979; Hum Genet 40:311–324, 1978; Ann Paediatr 174:126–127, 1950

236 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Hemolytic anemia with emphysema and cutis laxa Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa, corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005 Kabuki makeup syndrome – short stature, distinct face (long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, prominent malformed ears), cutis laxa, hyperextensible joints, syndactyly, fetal finger pads with abnormal dermatoglyphics, mental retardation JAAD S247–251, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 1981 Lenz-Majewski hyperostotic syndrome – cutis laxa, skeletal anomalies, and ambiguous genitalia Leprechaunism (Donohue syndrome) – cutis laxa-like wrinkling Am J Dis Children 122:442–445, 1971 Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high pitched voice; mutation in RIN2 JAAD 66:842–851, 2012 Marfan’s syndrome – lax skin in the neonate Marshall’s syndrome – Sweet’s syndrome followed by cutis laxa JAAD 66:842–851, 2012; AD 131:1175–1177, 1995; neutrophilic dermatosis with cutis laxa; aortic disease and other aneurysms Ped Derm 32:437–446, 2015; S Afr Med J 40:1016–1022, 1966; following Sweet’s syndrome (alpha 1 antitrypsin deficiency) Ped Derm 14:370, 1994; Sweet’s syndrome – healed AD 119:998–1002, 1983; acquired cutis laxa Ped Derm 26:452–457, 2009; Ped Derm 26:358–360, 2009 Menkes’ kinky hair syndrome – loose skin with wrinkling Ped Derm 14:347–350, 1997; silvery hair, generalized hypopigmentation, lax skin of brows, neck, and thighs Ped Derm 15:137–139, 1998; bone fractures with Wormian bones, cervical bone abnormalities, rib fractures, spurring of long bone metaphyses mimicking child abuse Society Pediatric Dermatology Annual Meeting, July, 2015 Michelin tire baby syndrome Neurofibromatosis Noonan’s syndrome – lax skin JAAD 46:161–183, 2002; Curr Prob in Derm VII:143–198, 1995; J Pediatr 66:48–63, 1965 Occipital horn syndrome Patterson David syndrome – pseudoleprechaunism Premature aging with short stature and pigmented nevi (Baraitser syndrome) Progeria AD 125:540–544, 1989 Prune belly syndrome (aplastic abdominal musculature syndrome) (Triad syndrome; Eagle-Barrett syndrome, urethral obstruction malformation sequence) – abdominal muscle hypoplasia, urinary tract abnormalities, bilateral cryptorchidism, pulmonary, skeletal, cardiac and gastrointestinal abnormalities; cerebriform appearance of abdomen; loose and wrinkled skin at birth Ped Derm 23:342–345, 2006 Pseudoxanthoma elasticum – with cutis laxa-like changes; deficiency of vitamin K-dependent clotting factors; mutation in GGCX gene BJD 161:635–639, 2009; JID 127:581–587, 2007 SCARF syndrome – ambiguous genitalia associated with skeletal abnormalities, cutis laxa, joint hyperextensibility, webbed neck, craniostenosis, psychomotor retardation, and facial abnormalities Am J Med Genet 34:305–312, 1989 Soto’s syndrome – joint hyperextensibility; cutis laxa; cerebral gigantism Ped Derm 33:e351–352, 2016; J Med Genet 36:51–56, 1999

Thrombocytopenia-absent radius syndrome (TAR syndrome) – cutis laxa of the neck; congenital thrombocytopenia, bilateral absent or hypoplastic radii, port wine stain of head and neck AD 126:1520– 1521, 1990; Am J Pediatr Hematol Oncol 10:51–64, 1988 Tricho-rhino-phalangeal syndrome type II (Langer-Giedion syndrome) – loose, redundant, wrinkled skin early; facies, bulbous nose, and sparse hair as in TRPS-I – microcephaly, exostoses Birth Defects X:147–164, 1974 Trisomy 13 (Patau syndrome) – neck Trisomy 18 – redundant skin, rocker-bottom feet, clenched fist Turner’s syndrome (XO in 80%) – peripheral edema at birth which resolves by age 2; redundant neck skin in newborn; cutis laxa of neck and buttocks; small stature, broad shield-shaped chest with widely spaced nipples, arms show wide carrying angle, webbed neck, low posterior hairline, low misshapen ears, high arched palate, short fourth and fifth metacarpals and metatarsals, hypoplastic nails, keloid formation, increased number of nevi; skeletal, cardiovascular, ocular abnormalities; increased pituitary gonadotropins with low estrogen levels JAAD 74:231–244, 2016; JAAD 50:767–776, 2004; JAAD 40:877–890, 1999 Urban-Rifkin_Davis syndrome – autosomal recessive; flattened midface; wide nasal bridge long philtrum, micrognathia, hypertelorism, periorbital fullness, receding forehead; severe pulmonary, gastrointestinal, and genitourinary abnormalities; mutation in LTBP4 JAAD 66:842–851, 2012 Weaver syndrome – prenatal overgrowth syndrome Am J Dis Child 138:1113–1115, 1984 Werner’s syndrome Wiedemann-Rautenstrauch syndrome (neonatal pseudohydrocephalic progeroid syndrome of Wiedemann-Rautenstrauch) Clin Genet 51:200–204, 1997; Eur J Pediatr 136:245–248, 1981 Wrinkly skin syndrome – autosomal recessive Clin Genet 38:307– 313, 1990; same as cutis laxa with growth and developmental delay; increased palmoplantar creases, prominent venous pattern over chest, mental retardation, microcephaly, hypotonia (joint laxity), musculoskeletal (decreased muscle mass, hip dislocation, winging of scapulae, vertebral deformities), short stature, craniofacial abnormalities, and connective tissue abnormalities Ped Derm 23:225–230, 2006; Am J Med Genet 101:213–220, 2001; Ped Derm 6:113–117, 1999; Am J Med Genet 85:194, 1999; Clin Genet 4:186–192, 1973

VASCULAR LESIONS Edema – recovery from severe edema Rapidly involuting congenital hemangioma – of face with cutis laxa-like appearance; post-involutional subcutaneous atrophy Soc Ped Derm Annual Meeting, July, 2006 Urticarial vasculitis associated with IgA myeloma– acquired cutis laxa JAAD 60:1052–1057, 2009 Varicose veins – acquired localized elastolysis Clin Exp Dermatol 20:492–495, 1995

CUTIS VERTICIS GYRATA PRIMARY CUTIS VERTICIS GYRATA Cataract Am J Ment Defic 57:613–631, 1953 Cerebral palsy Acta Med Scand 175:115–127, 1964

Cutis Verticis Gyrata Epilepsy Neurology 47:573–575, 1996; Indian J Dermatol Venereol Leprol 62:269–270, 1996 Familial spastic paraplegia Rinsho Shinkeigaku 28:97–101, 1988 Keratoconus Acta Med Scand 175:115–127, 1964 Mental retardation Australas J Dermatol 48:9194, 2007; Acta DV 86:458–459, 2006; Dermatology 191:292–294, 1995; in LennoxGastaut syndrome Neurol Sci 22:253–256 , 2001

237

NEOPLASTIC DISORDERS Angiosarcoma Clin Exp Dermatol 36:806–808, 2011 Cellular blue nevi, congenital Indian J Dermatol 61:126, 2016 Cylindroma Dermatofibroma Fibromas Ann Surg 118:154–158, 1943

Microcephaly in Cohen syndrome Eur J Hum Genet 17:1076–1079, 2009

Glioblastoma multiforme J Comput Assist Tomogr 32:119–123, 2008

Nystagmus Am J Ment Defic 57:613–631, 1953

Leiomyomatosis, cutaneous BJD 163:1337–1339, 2010

Pachydermoperiostosis (Touraine-Solente-Gole’ syndrome) Int J Dermatol 48:882–885, 2009; Ped Derm 20:358–360, 2003;

Leukemia – acute monoblastic leukemia Acta DV 73:148–149, 1993; acute myelogenous leukemia Am J Hematol 8:415–418, 1980

J Dermatol 27:106–109, 2000

Lymphoma – T-cell lymphoma Indian J DV Leprol 81:631–633, 2015

Periventricular calcifications Rofo 179:1074–1075, 2007

Melanocytic nevi J Pediatr Ophthalmol Strabismus 21:47, 2010; Hautarzt 61:929–932, 2010; cerebriform intradermal nevus Dermatol Online J 16:14, 2010; Clin Exp Dermatol 34:e840–842, 2009; congenital Ped Derm 25:43–46, 2008; Ped Derm 24:141–143, 2007; Austral J Dermatol 48:91–94, 2007; Ped Derm 20:358–360, 2003; J Eur Acad DV 1:529, 531, 2002; Dermatology 186:294–297, 1993; Ann Plast Surg 19:84–88, 1987

Polymicrogyria Epilepsia 37:284–286, 1996 Retinitis pigmentosa in Cohen syndrome Eur J Hum Genet 17:1076–1079, 2009 Schizophrenia Biol Psychiatry 25:636–638, 1989 Strabismus Am J Ment Defic 57:613–631, 1953

Intraventricular ependymoma West Afr J Med 18:130–132, 1999

Meningioma J Comput Assist Tomogr 32:119–123, 2008

SECONDARY CUTIS VERTICIS GYRATA

Metastases – intraductal breast carcinoma J Coll Phys Surg Pak 22:120–122, 2012

AUTOIMMUNE DISEASES

Neurocristic hamartoma Am J Dermatopathol 36:e66–69, 2014

Dermatomyositis Ped Derm 20:358–360, 2003

Neurofibroma Clin Exp Dermatol 3:319–322, 1978

Hyper IgE syndrome Acta DV 89:413–414, 2009

Pituitary microadenoma J Comput Assist Tomogr 32:119–123, 2008 Schwannoma J Comput Assist Tomogr 32:119–123, 2008

CONGENITAL LESIONS Neonatal Ped Derm 1:153–156, 1983

PARANEOPLASTIC DISORDERS Internal malignancy AD 125:434–435, 1989

DRUGS Anabolic steroids Clin Exp Dermatol 31:134–136, 2006

PRIMARY CUTANEOUS DISEASES

Vemurafenib and whole brain radiation J Clin Oncol 32:e54–56, 2014

Acanthosis nigricans Am J Ment Defic 57:613–631, 1953

INFECTIONS AND INFESTATIONS

Acne conglobate J Eur Acad Dermatol Venereol 19:772–774, 2005; J Eur Acad Dermatol Venereol 18:499–502, 2004

HIV-related lipodystrophy Dermatol Res Pract 2013:941740

Alopecia areata Yonsei Med J 51:612–614, 2010

Syphilis

Atopic dermatitis Australas J Dermatol 48:91–94, 2007 Darier’s disease Acta DV 86:59–60, 2006

INFILTRATIVE DISORDERS Amyloidosis – primary systemic amyloidosis Indian J Dermatol Venereol Leprol 75:394–397, 2009; Ped Derm 20:358–360, 2003 Cutaneous focal mucinosis Scleromyxedema Indian Dermatol Online J 7:186–189, 2016

SYNDROMES Apert’s syndrome Am J Med Genet 44:82–89, 1992 Autosomal dominant insulin resistant syndrome Clin Exp Dermatol 25:125–128, 2000

Acromegaly NEJM 380:e31, 2019; Int J Dermatol 47:164, 2008; Indian J Dermatol Venereol Lerol 74:139–141, 2008; Endocr Pract 8:475, 2002

Beare-Stevenson syndrome – acanthosis nigricans, hypertelorism, cleft palate, bifid scrotum, large umbilical stump, skin furrows of the face, hands, feet, axilla, and/or perineum, cutis verticis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital anomalies, early death Ped Derm 20:358–360, 2003; Am J Med Genet 44:82–89, 1992; BJD 81:241, 1969

Graves’ disease Thyroid 16:815–816, 2006

Cohen syndrome Eur J Hum Genet 17:1076–1079, 2009

Mental retardation Ped Derm 20:358–360, 2003

Cornelia de Lange syndrome Am J Med Genet C Semin Med Genet 145C:248–260, 2007

METABOLIC DISORDERS

Myxedema Thyroid 16:815–816, 2006; Int J Dermatol 38:781–783, 1999 Pseudoacromegaly JAAD 48:962–965, 2003

Cutis verticis gyrata-mental deficiency syndrome Clin Dysmorphol 7:131–134, 1998

Thyroid aplasia Ped Derm 20:358–360, 2003

Ehlers-Danlos syndrome Ped Derm 20:358–360, 2003;

238 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Proc Staff Meet Mayo Clin 28:631–635, 1953 Empty sella syndrome Eur J Intern Med 19:e23–25, 2008; J Comput Assist Tomogr 32:119–123, 2008 Fragile X syndrome Am J Med Genet 38:249–250, 1991; Lancet July 29;2(8657):279, 1989 Hereditary neuralgic amyotrophy Neurology 57:1963–1968, 2001 Klinefelter’s syndrome Am J Med Genet 103:249–251, 2001 Lennox-Gastaut syndrome (retardation with EEG abnormalities) Dev Med Child Neurol 16:196–200, 1974 Noonan’s syndrome Australas J Dermatol 48:91–94, 2007; Ped Derm 22:142–146, 2005 Tuberous sclerosis Ped Derm 20:358–360, 2003; Am J Ment Defic 57:613–631, 1953

Cyst of first branchial cleft (congenital postauricular swelling) Ped Derm 19:246–249, 2002 Dacryocystocele – congenital blue nodule of medial lower eyelid; blue, pink, or red cystic mass JAAD 61:1088–1090, 2009; Laryngoscope 113:37–40, 2003 Dermoid cyst – midline of nose, lateral eyebrow, scrotum, sternum, perineal raphe, and sacral areas Ped Derm 30:706–711, 2013; Curr Prob in Derm 8:137–188, 1996; Neurosurg Clin N Am 6:359–366, 1995; AD 107:237–239, 1973; presternal dermoid cyst – subcutaneous nodule Ped Derm 30:128–130, 2013 Diastrophic dysplasia – cystic masses of ears Ectopic respiratory epithelium BJD 136:933–934, 1997 Encephalocele Ped Neurosurg 27:214–217, 1997

Turner’s syndrome Clin Dysmorphol 14:149–150, 2005

Epstein’s pearls – keratinous cysts of palatal or alveolar mucosa in neonates Int Dent J 27:261–262, 1988

TRAUMA

Eruption cyst, congenital – fluctuant swelling; blue-red to black translucent, elevated compressible over alveolar ridge; overlie teeth about to erupt; epithelial cyst of oral mucosa on gingival margin Ped Derm 27:671–672, 2010

Post-traumatic Traction alopecia Int J Dermatol 31:671–672, 1992

Follicular atrophoderma (perioral, pigmented), milia, and epidermoid cysts Ped Derm 25:474–476, 2008

VASCULAR LESIONS

Foregut cystic developmental malformation of scapula – soft skin colored nodule of scapula Ped Derm 29:363–364, 2012

Intracranial aneurysm West Afr J Med 18:130–132, 1999

Foreskin cysts

CYSTS WITH OR WITHOUT DRAINAGE

Heterotopic brain tissue – bald cyst of the scalp – hair collar sign AD 125:1253–1256, 1989

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Rheumatoid arthritis – bursal cyst with cholesterol crystals of left elbow NEJM 369:1945, 2013; multiple epidermoid cysts J Hand Surg 25:768–771, 2000 Scleroderma – soft cystic nodules (focal mucinosis) over interphalangeal joints BJD 136:598–600, 1997

CONGENITAL ANOMALIES Branchial cleft cyst and/or sinus and/or fistula – cyst overlying anterior border of the sternocleidomastoid muscle Textbook of Neonatal Dermatology, p. 119, 2001; Int J Oral Maxillofac Surg 25:449–452, 1996; Int J Dermatol 19:479–486, 1980; differential diagnosis includes malignant or tuberculous lymphadenopathy, parotid or thyroid tumor, thymopharyngeal cyst, thyroglossal cyst, dermoid cyst, teratoma, carotid body tumor, hemangioma, neurofibroma; of scalp Ped Derm 27:204–206, 2010 Bronchogenic cyst – keratotic papule, sinus tract or cyst in midline at the suprasternal notch, neck, shoulders, back or chest AD 142:1221–1226, 2006; Ped Derm 15:277–281, 1998; Int J Derm 37:137–140, 1998; JAAD 31:120–122, 1994; subcutaneous bronchogenic cyst J Pediatr Surg 23:993–995, 1988 Cervico-thymic cyst – resembles branchial cleft cyst Congenital sinus or cyst of genitoperineal raphe (mucous cysts of the penile skin) Cutis 34:495–496, 1984; AD 115:1084–1086, 1979 Cutaneous ciliated (mullerian) cyst – lower legs of women and perianal region young females Ped Surg Int 30:548, 2014Pathol Int 51:970–973, 2001

Hereditary perioral pigmented follicular atrophoderma with milia-like epidermoid cysts BJD 139:713–718, 1998

Heterotopic salivary gland tissue JAAD 31:120–122, 1994 Hypotrichosis, eyelid cysts, and hypodontia Laryngocele/pharyngocele with external component Am Fam Physician 42:665–668, 1990 Median raphe canal of the ventral penis – with or without median raphe cysts; yellow cystic papules Ped Derm 27:667–669, 2010; Am J Dermatopathol 23:320–324, 2001; Ped Derm 15:191–193, 1998; Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 80; Cutis 34:495–496, 1984, JAAD 26:273–274, 1992; AD 115:1084–1086, 1979; differential diagnosis includes epidermoid or dermoid cysts, urethral diverticulosis, apocrine hidrocystoma Meningeal heterotopia (ectopic rests of meningeal tissue that have lost central nervous system connection) and rudimentary or atretic meningoceles – exophytic nodular or cystic mass of occipital or parietal scalp – normal skin; glistening or bullous appearance, alopecia, hair collar Ped Derm 32:161–170, 2015 Meningocele, rudimentary – scalp cyst AD 137:45–50, 2001 Meningoencephalocele – midline of bridge of nose, differentiate from dermoid cyst Plast Reconstr Surg 57:692–699, 1976 Midline anterior neck inclusion cyst – sign of midline fusion defect JAMADerm 156:806, 2020 Midline cervical cleft Int J Derm 19:489–486, 1980 Milia Mucocele of lacrimal sac – blue cystic swelling below medial canthus Mucous cyst of retrorectal space Omphalomesenteric duct cyst – umbilical or periumbilical

Cysts with or Without Drainage 239 Pearls (milia) in newborn of areolae, scrotum, and labia majora of newborn Pre-auricular pits, sinuses and cysts  Branchio-oto-renal syndrome (BOR) J Dent Anesth Pain Med17:215–217, 2017   Treacher-Collins syndrome  Goldenhar syndrome – oculo-auriculo-vertebral spectrum (OAVS)  Chromosome 4 deletion syndrome Am J Dis Child 122:421–425, 1971  Melnick-Fraser syndrome (brachio-oto-renal syndrome) Ped Derm 13:507–508, 1998   Cat eye syndrome Hum Genet 57:148–158, 1981 Presternal ciliated cyst (lower neck) AD 120:240–242, 1984 Sacral meningeal cyst Neurosurgery 29:223–231, 1991

Vemurafenib – cystic lesions of face, keratosis pilaris-like eruptions, seborrheic dermatitis rashes, hyperkeratotic plantar papules, squamous cell carcinoma AD 148:357–361, 2012

EXOGENOUS Acne cosmetica Bromoderma Chloracne (halogenated aromatic compounds, agent orange) Foreign body, including blackthorn inflammation Gold acupuncture – multiple epidermal cysts Ann Dermatol 26:405–406, 2014 Iododerma

Seroma (lymphocele) Spinal dysraphism with overlying dermoid cyst, protrusion, dimple, sinus, lipoma, faun tail nevus, hemangioma, port wine stain AD 114:573–577, 1978; AD 112:1724–1728, 1976

INFECTIONS AND INFESTATIONS

Temporomandibular joint cyst Am J Otolaryngol 21:331–332, 2000

Actinomycosis JAAD 29:308–311, 1993

Teratoma JAAD 31: 120–122, 1994

AIDS – lymphoepithelial cysts of the parotid gland Alternariosis – subcutaneous cyst Clin Inf Dis 32:1178–1187, 2001

Thyroglossal duct cyst and/or sinus – midline cervical cleft with sinus tract AD 136:925–930, 2000; Am J Neuroradiol 20:579–582, 1999; JAAD 26:885–902, 1992; J Pediatr Surg 19:437–439, 1984

Brucellosis – presenting as a Baker’s cyst Clin Inf Dis 22:872–873, 1996

Urachal cyst (partial patency of the urachus) – tender midline swellings between the umbilicus and symphysis pubis Br J Urol 28:253–256, 1956

Coccidioidomycosis SKINMed 14:142–144, 2016

Urethral retention cyst – white papule at urethral opening of males

Chromomycosis Pathology 11”389–392, 1979 Cysticercosis (C. cellulosae) (larval form of Toxocara solium) – papulonodules, subcutaneous cysts, cysts in skeletal muscles, mucous membranes, seizures (neurocysticercosis) JAAD 75:19–30, 2016 Dental sinus and cyst – dental sinus mimicking acne cyst

DEGENERATIVE DISEASES Digital myxoid cyst (mucous pseudocyst) Dermatol Clin 33:207– 241, 2015; Arthr Rheum 20:997–1002, 1977; digital myxoid cyst J Derm Surg Oncol 13:723–727, 1987

DRUG-INDUCED Drug-induced acneiform eruptions – glucocorticoids, halogenated compounds, phenytoin, carbamazepine, gabapentin, lithium, isoniazid, growth hormone, oral contraceptives, anabolic steroids, Vitamin B12 Cyclosporine – multiple epidermoid cysts Cutis 50:36–38, 1992; Dermatologica 172:24–30, 1986; cysts of face in infancy AD 145:797–799, 2009 Dabrafenib – keratoacanthomas; plantar calluses, seborrheic keratosis, acneiform eruptions, epidermoid cysts, alopecia, verruca vulgaris BJD 167:1153–1160, 2012 Enfuvirtide – injection site reaction JAAD 49:826–831, 2003 Epidermal growth factor inhibitors – multilobular inflamed cysts JAAD 55:657–670, 2006 Imiquimod – multiple clustered eruptive epidermoid cysts Dermatology 215:352–353, 2007 Nivolumab – lichen planus follicular tumidus mimicking cystic acne JAMADerm 155:1197–1198, 2019 Tacrolimus – epidermoid cysts Ann Dermatol 23:S182—184, 2011

Dracunculosis Echinococcosis – dog tapeworm; hydatid cyst; giant intraperitoneal cyst Focal myositis Cutis 54:189–190, 1994 Herpes zoster – multiple epidermoid cysts at site of healed herpes zoster in renal transplant patient Clin Exp Dermatol 28:555–556, 2003 Leprosy – primary neuritic leprosy with nerve abscess AD 130:243– 248, 1994 Lobomycosis Mycobacterium haemophilum Clin Inf Dis 33–330–337, 2001 Mycobacterium tuberculosis – scrofuloderma Myiasis, furuncular – Dermatobia hominis – scalp cyst in a child Ped Derm 15:116–118, 1998; mimicking ruptured epidermoid cyst Can J Surg 33:145–146, 1990; house fly BJD 76:218–222, 1964; New World screw worm (Cochliomyia), Old World screw worm (Chrysomya), Tumbu fly (Cordylobia) BJD 85:226–231, 1971; black blowflies (Phormia) J Med Entomol 23:578–579, 1986; greenbottle (Lucilia), bluebottle (Calliphora), flesh flies (Sarcophaga, Wohlfartia) Neurosurgery 18:361–362, 1986; rodent botflies (Cuterebra) JAAD 21:763–772, 1989; human botflies (Dermatobia hominis) AD 121:1195–1196, 1985; AD 126:199–202, 1990 Nocardiosis AD 130:243–248, 1994 Phaeohyphomycosis – diffuse infiltrated pigmented plaques; subcutaneous cysts, abscesses, ulcerated plaques, hemorrhagic pustules, necrotic papulonodules, cellulitis The Dermatologist June 2019, p.23–24; JAAD 75:19–30, 2016; JAAD 40:364–366, 1999;

240 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 JAAD 28:34–44, 1993; AD 127:721–726, 1991; JAAD 19:478–481, 1988; AD 123:1346–1350, 1987

Cystic teratoma – large cystic lesion of face Soc Ped Derm Annual Meeting, July, 2006

Tinea profunda cysticum – Trichophyton rubrum; giant cysts JAAD 54:S11–13, 2006

Dermoid cyst in adult – skin colored nodule of nose JAMA Derm 149:609–614, 2013

Verruca vulgaris – plantar epidermoid cysts contain human papillomavirus (HPV 60) J Cutan Pathol 16:375–381, 1989

Eccrine tumors SKINMed 14:175–180, 2016

INFLAMMATORY DISEASES Dissecting cellulitis of the scalp (perifolliculitis capitis abscedens et suffodiens) JAAD 62:534–536, 2010; J Derm Surg Oncol 18:877– 880, 1992 Hidradenitis suppurativa – nodulocystic lesions of posterior neck and post-auricular areas AD 147:1343–1344, 2011 Myospherulosis JAAD 38:274–275, 1998; AD 127:88–90, 1991; JAAD 21:400–403, 1989 Pilonidal cyst and sinus Surg Clin North Am 74:1309–1315, 1994 Subcutaneous fat necrosis of the newborn Cutis 70:169–173, 2002

METABOLIC DISORDERS Calcinosis cutis Idiopathic calcinosis of the scrotum

NEOPLASTIC Acrospiroma (benign acrospiroma) Cutis 83:12,21, 2009 Bartholin’s cyst Basal cell carcinoma – cystic basal cell carcinoma; basal cell carcinoma arising in the wall of an epidermal inclusion cyst Derm Surg 27:585–586, 2001 Basal cell nevus (linear basal cell nevus) – resemble comedones; usually linear translucent telangiectatic papules, may ulcerate; macular hypopigmentation, alopecia, cysts, striae Cutis 46:493– 494, 1990; BJD 74:20–23, 1962

Epidermoid cyst – plantar epidermoid cysts, HPV-60-related BJD 152:961–967, 2005; multiloculated epidermoid cyst – often of plantar surface JAAD 58:S120–122, 2008; Dermatol Surg 31:1323– 1324, 2005; BJD 151:943–945, 2004; Dermatol Surg 28:639–640, 2002; BJD 144:217–218, 2001; of the skull Plast Reconstr Surg 97:1246–1248, 1996 Eruptive vellus hair cysts Cutis 102:367–369, 2018; Ped Derm 29:367–369, 2012; AD 113:500–503, 1977; dark brown papules Ped Derm 31:515–516, 2014; with pachyonychia congenita J Dermatol 26:402–404, 1999 Fibrous hamartoma of infancy Ped Derm 7:157, 1990 Follicular cysts – multiple pigmented follicular cysts BJD 134:758– 762, 1996 Folliculosebaceous cystic hamartoma – skin colored papule or nodule of central face or scalp; pedunculated or dome-shaped and umbilicated; multiple cobblestoned lesions of scrotum BJD 157:833–835, 2007; Clin Exp Dermatol 31:68–79, 2006; AD 139:803–808, 2003; JAAD 34:77–81, 1996; Am J Dermatopathol 13:213–220, 1991; J Cutan Pathol 7:394–403, 1980Ganglion cyst J Hand Surg (Br) 15:342–346, 1990 Generalized follicular hamartoma – with trichilemmal cysts and palmar pits AD 107:435–438, 1973 Hidradenoma papilliferum JAAD 41:115–118, 1999 Hidrocystoma – apocrine or eccrine – clear or blue Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, pp.153–155; eyelid or facial cyst AD 137:657– 662, 2001; AD 134:1627–1632, 1998; JAAD 26:780–782, 1992; AD 115:194–200, 1979; of the penis AD 142:1221–1226, 2006 Hybrid cysts – with features of eruptive vellus hair cysts, steatocystoma, and epidermoid cyst Am J Dermatopathol 18:645–649, 1996 Kaposi’s sarcoma – cystic Kaposi’s sarcoma; fluid-filled cysts JAAD 59:179–206, 2008

Ciliated cyst of vulva JAAD 32:514–515, 1995

Lymphoma – subcutaneous T-cell lymphoma with cytophagic histiocytic panniculitis and membranocystic lesions Am J Dermatopathol 20:276–280, 1998; pilotropic (folliculotropic) CTCL – cystic lesions, follicular keratotic papules, acneiform, comedo-like lesions AD 146:607–613, 2010; JAAD 62:418–426, 2010; BJD 152:193–194, 2005; JAAD 48:448–452, 2003; Ann DV 126:243–246, 1999; AD 132:683–687, 1996; epidermoid cysts AD 138:191–198, 2002; eruptive epidermoid cysts Dermatology 187:273–277, 1993

Clear cell hidradenoma (eccrine acrospiroma) Cutis 58:349–351, 1996; AD 128:1533–1538, 1992

Mammary-like glands of the vulva – cysts Int J Gynecol Pathol 14:184–188, 1995

Clustered cysts   Milia en plaque JAAD 21:311–313, 1989   Pilotropic CTCL AD 132:683–687, 1996  CTCL JAAD 29:331–334, 1993  Eruptive epidermal cysts after CTCL therapy JAAD 25:940–943, 1991  Familial subconjunctival cysts in nevoid basal cell carcinoma syndrome AD 123:23–24, 1987

Marginal cysts of eyelids – occluded glands of Moll; painless white or yellow cyst of lower eyelid close to lacrimal punctum

Bowen’s disease – arising in the wall of an epidermal inclusion cyst Derm Surg 27:585–586, 2001 Chalazion – personal observation Chondroid syringoma Ciliated cyst – of the lower leg Pathol Int 49:354–357, 1999; legs of young women; perianal Am J Dermatopathol 19:93–96, 1997; sole BJD 132:488–490, 1995

Metaplastic synovial cysts JAAD 41:330–332, 1999 Metastases – gastric carcinoma (epidermoid cyst-like); adenocarcinoma of the lung JAAD 36:644–646, 1997; bladder – cystic metastases J R Soc Med 80:314–315, 1987 Microcystic adnexal carcinoma Milia

Cysts with or Without Drainage Mucocele AD 101:673–678, 1970

PHOTODERMATOSIS

Muellerian cyst of vulva

Favre-Racouchot syndrome Ann DV 121:721–723, 1994

Myxoid cyst, digital J Derm Surg Oncol 13:723–727, 1987 Nevus comedonicus, inflammatory JAAD 38:834–836, 1998 Nevus tricholemmocysticus – multiple pilar cysts; filiform hyperkeratoses of face and arm, comedo-like plugs, osteomalacia, bone lesions; verrucous papules, yellow plaques, cysts; Blaschko distribution Ped Derm 28:286–289, 2011; JAAD 57(Suppl):S72–77, 2007 Olecranon bursal cyst – personal observation Paget’s disease – arising in the wall of an epidermal inclusion cyst Derm Surg 27:585–586, 2001 Pilar cyst/ proliferating pilar cyst Pilomatrixoma Pediatr Rev 11(9):262–267, 1990; Cancer 45:2368– 2373, 1980 Pilomatrix carcinoma (cyst-like) JAAD 23:104–108, 1990 Pilonidal cyst – personal observation Post-auricular cysts AD 107:237–239, 1993   Branchial cleft cyst   Dermoid cyst   Epidermoid cyst   Pilar cyst   Pseudocyst of the auricle   Steatocystoma multiplex Proliferating epithelial cysts J Cutan Pathol 22:394–406, 1995 Retention cyst from glands of Zeis Retroauricular, follicular, and keratotic plaques with multiple follicular cysts Med Cutano Ibero Lat Am 13:331–334, 1985 Rhabdomyomatous mesenchymal hamartoma – cystic mass Ped Derm 32:256–262, 2015 Sebaceoma Sebaceous carcinoma – mimicking chalazion of eyelid Am J Surg Pathol 2:305–311, 1978; Trans Am Acad Ophthalmol Otol 72:619– 640, 1968 Squamous cell carcinoma – arising in the wall of an epidermal inclusion cyst Am J Dermatopathol 21:174–177, 1999; Derm Surg 27:585–586, 2001 Steatocystoma – giant cyst of face BJD 167:1395–1397, 2012 Syringocystadenoma papilliferum Syringomas, including eruptive syringomas AD 121:756, 1985; vulvar – discrete white cystic papules JAAD 48:735–739, 2003

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PRIMARY CUTANEOUS DISEASES Acne fulminans Acne rosacea – lupus miliaris disseminate faciei; multiple epidermal cysts Dermatology 214:272–273, 2007 Acne vulgaris Atopic dermatitis – pretibial bursitis JAAD 30:737–742, 1994 Darier’s disease – comedonal Darier’s disease; nodules, cysts, ice pick scars BJD 162:687–689, 2010 Endosalpingiosis – ectopic fallopian tube epithelium; umbilical cystic nodule BJD 151:924–925, 2004 Intramuscular hydatid cyst – giant skin colored subcutaneous tumor (25 × 15 cm) Clin Inf Dis 61:1707, 1759–1760, 2015 Inguinal hernia NEJM 355:601, 2006 Pyoderma faciale AD 128:1611–1617, 1992 Psoriasis – bursal sac of elbow

SYNDROMES Atrichia with keratin cysts – face, neck, scalp; then trunk and extremities Ann DV 121:802–804, 1994 Atrichia with papular lesions – autosomal recessive; follicular cysts AD 139:1591–1596, 2003; JAAD 47:519–523, 2002 Birt-Hogg-Dube syndrome – multiple cystic lesions of face JAMADerm 151:770–774, 2015; epidermoid cysts; mutation of FLCN gene BJD 162:527–537, 2010 Branchio-oto-renal syndrome – pre-auricular sinus or cyst Clin Genet 9:23–34, 1976 Carney complex – multiple myxomatous cysts Cowden’s syndrome – epidermoid cysts Ehlers-Danlos syndrome – firm cyst-like nodules (spheroids) of shins and forearms JAAD 46:161–183, 2002 Eyelid cysts, hypodontia and hypotrichosis JAAD 10:922–925, 1984 Familial dyskeratotic comedones Genetic Skin Disorders, Second Edition, 2010, pp.262–264

Trichilemmal cyst nevus – multiple subcutaneous nodules with cystic lesions with and without comedones in Blaschko distribution, filiform hyperkeratoses JAAD 57:S72–77, 2007

Gardner’s syndrome – epidermoid cysts – of face, scalp, extremities, and trunk; desmoid tumors (subcutaneous nodule/tumor); pilomatrixoma-­like epidermoid cysts; fibromas; neurofibromas; leiomyomas, lipomas; supernumerary or unerupted teeth; congenital hypertrophy of retinal pigmented epithelium JAAD 68:189–209, 2013; JAAD 58:902–903, 2008; Curr Prob Derm 14:41–70, 2002; Dermatol Clin 13:113–125, 1995; Am J Hum Genet 57:1151–1158, 1995; familial pilomatrixomas Ped Derm 12:331–335, 1995

Trichoblastic infundibular cyst with follicular germinative differentiation J Cut Pathol 43:191–199, 2016

Goltz’s syndrome – periocular multiple apocrine hidrocystomas JAAD 65:1066–169, 2011

Trichoblastoma – with dilated pore JAAD 54:357–358, 2006

Hereditary perioral pigmented follicular atrophoderma with milia-like epidermoid cysts BJD 139:713–718, 1998

Teratoid cyst of post-auricular region – 6 types of keratin-filled cysts: epidermoid, dermoid, teratoid, keratinous, trichilemmal, and keratoma cysts Case Rep Pathol 2017:9235925

Trichoepithelioma, cystic Verruciform xanthoma, cystic JAAD 25:330–331, 1991 Verrucous cyst J Cutan Pathol 20:411–417, 1993; AD 127:1810– 1812, 1991 Vulvar epidermal cysts – personal observation

Hidradenitis suppurativa, Dowling-Degos disease, and multiple epidermal cysts (new follicular occlusion triad) Clin Exp Dermatol 29:622–624, 2004 Howel-Evans syndrome – epidermal inclusion cysts Genetic Skin Disorders, Second Edition, 2010, pp.63–65

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Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, follicular occlusion triad, scalp cysts, nodules (trichilemmal tumors, squamous cell carcinoma), bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation JAAD 69:127–134, 2013; Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377– 382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; JAAD 19:1124–1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915 LEOPARD (Moynahan’s) syndrome – CALMs, granular cell myoblastomas, steatocystoma multiplex, small penis, hyperelastic skin, low set ears, short webbed neck, short stature, syndactyly JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; J Dermatol 25:341–343, 1998; Am J Med 60:447–456, 1976; AD 107:259–261, 1973 Lowe syndrome (oculocerebrorenal disease) – multiple epidermal cysts; OCRL1 gene Ann Dermatol 22:444–446, 2010 Multicentric reticulohistiocytosis – cystic swellings around tendon sheaths

Rubenstein-Taybi syndrome – pilomatrixomas JAAD 46:161–183, 2002; JAAD 46:159, 2002 SAPPHO syndrome Schopf-Schulz-Passarge syndrome – eyelid cysts (hidrocystomas), palmoplantar keratoderma, hypotrichosis, decreased number of teeth, brittle and furrowed nails; onychodysplasia; mutation in WNT10A BJD 171:111–1214, 2014; Ped Derm 30:491–492, 2013; JAAD 65:1066–1069, 2011; Acta DV 88:607–612, 2008; AD 140:231–236, 2004; BJD 127:33–35, 1992; JAAD 10:922–925, 1984; Birth Defects XII:219–221, 1971 Schwartz-Jampel syndrome (Stuve-Wiedemann syndrome) – autosomal recessive; primary skeletal dysplasia; joint restrictions; hyperthermic episodes, dysautonomia, respiratory and feeding difficulties, early mortality, eruptive vellus hair cysts and clefted tongue Ped Derm 37:381–382, 2020 Steatocystoma multiplex SKINmed 12:267–269, 2014; JAAD 43:396–399, 2000; AD Syphilol 36:31–36, 1937; steatocystoma multiplex, partial congenital absence of secondary dentition, persistence of primary dentition; mutation in keratin 17 gene BJD 161:1396–1398, 2009 Stuve-Wiedemann syndrome – clefted tongue and multiple eruptive vellus hair cysts Ped Derm 37:381–382, 2020 Tuberous sclerosis – folliculocystic and collagen hamartoma – comedo-­like openings, multilobulated cysts, scalp cysts and nodules JAAD 66:617–621, 2012

Nevoid basal cell carcinoma syndrome (Gorlin syndrome) – multiple epidermoid cysts in 50%; Meibomian gland cysts of eyelids BJD 164:245–256, 2011; AD 145:1341–1342, 2009; JAAD 42:939–969, 2000; Ped Derm 17:484–486, 2000; epidermoid cyst of finger BJD 145:508–509, 2001; cutaneous keratocysts of nevoid basal cell carcinoma syndrome (blue cysts) JAAD 14:572–576, 1986; acral cutaneous keratocysts BJD 135:810–812, 1996; with palmar epidermoid cyst, milia, and maxillary cysts BJD 145:508– 509, 2001

TOXINS

Ocular ectodermal syndrome – epibulbar dermoid and cutaneous myxovascular hamartoma Br J Ophtalmol 84:669–670, 2000

Acne mechanica

Pachyonychia congenita – facial steatocystoma multiplex cysts Ped Derm 35:517–518, 2018; BJD 171:1565–1567, 2014; epidermal inclusion cysts; Jackson-Lawler pachyonychia congenita type 2 (MIM 167210) – white milia-like cysts at birth JAAD 38:1007–1009, 1998; associated with steatocystoma multiplex BJD 114:367–370, 1986; large facial cysts BJD 148:452–455, 2003; natal teeth, bushy eyebrows, follicular keratoses, angular cheilitis, unruly hair, thick nails, palmoplantar keratoderma with hyperhidrosis, hoarseness, cysts oral leukokeratosis; mutations in KRT6A, KRT6B, KRT6C, KRT16, KRT17 BJD 171:343–355, 2014 Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts within a family Dermatology 196:392–396, 1998 Rombo syndrome – papules and cysts of the face and trunk, basal cell carcinomas, vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, peripheral vasodilatation with cyanosis Ped Derm 23:149–151, 2006; BJD 144:1215–1218, 2001; JAAD 39:853–857, 1998; Acta DV 61:497–503, 1981

Chloracne – dioxin; chloracne with cysts BJD 143:1067–1071, 2000; pale yellow keratin cysts and large prominent comedones on malar cheeks, post-auricular areas, ears, neck, and scrotum JAAD 13:539–558, 1985

TRAUMA Amputation stump frictional epidermoid cysts Acta DV 43:56–67, 1963 Pseudocyst of the auricle Cutis 77:102–104, 2006; BJD 122:699– 704, 1990; AD 125:528–530, 1989; Arch Otolaryngol 83:197–202, 1966; associated with atopic dermatitis JAAD 56:858–861, 2007

VASCULAR Cystic angiomatosis Can J Surg 30:277–279, 1987 Lymphangioma circumscriptum, diffuse BJD 83:519–527, 1970 Lymphatic malformation (cystic hygroma) JAAD 56:353–370, 2007; Rook p. 2294, 1998, Sixth Edition; lymphatic malformations are associated with the following syndromes: Soc Ped Derm Annual Meeting, July, 2006   Multiple lymphangiomatosis syndrome   Noonan’s syndrome  Trisomies   Turner’s syndrome

 EAFNESS OR HEARING D IMPAIRMENT, CUTANEOUS MANIFESTATIONS

SYNDROMES Achondroplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.234–235 Acrodysostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.190–191

AUTOIMMUNE DISEASES

Albinism with deafness

Sjogren’s syndrome – sensorineural hearing loss A Clinician’s Pearls and Myths in Rheumatology pp.107–130; ed John Stone; Springer 2009

Albright’s hereditary osteodystrophy (pseudohypoparathyroidism) – osteoma cutis – periarticular calcified or ossified nodules (ectopic ossification); short stocky build; round face; low flat nasal bridge; short neck, brachymetaphalangism and brachydactyly; developmental delay, cataracts, hearing loss, seizures, poor dentition, basal ganglia calcification, osteomalacia, rickets, osteoporosis JAMA Derm 149:975–976, 2013; JAAD 15:353–356, 1986; AD 104:636– 642, 1971; Medicine 37:317–352, 1958

DRUGS Thalidomide embryopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.370–371

Alezzandrini’s syndrome – unilateral degenerative retinitis, ipsilateral facial vitiligo, poliosis, with or without deafness Arch Iranian Med 4, April, 2001; Ophthalmologica 147:409–419, 1964

INFECTIONS

Alkaptonuria

Cytomegalovirus infection Otolaryngol Pol 68:303–307, 2014 Herpes zoster – cranial nerve VIII involvement NEJM 369;255–263, 2013 Lassa fever – capillary leak syndrome with severe swelling of head and neck, eighth nerve deafness; oral ulcers, tonsillar patches JAAD 65:1213–1218, 2011 Malaria J Infect Chemother 23:56–58, 2017 Measles Mumps JAAPA 31:19–22, 2018 Rocky Mountain spotted fever – acute transient hearing loss MMWR 65:1–44, May 13, 2016 Congenital rubella – blueberry muffin baby and deafness Syphilis, congenital, neurosyphilis – Hutchinson’s triad – interstitial keratitis, VIII nerve deafness, Hutchinson’s teeth JAAD 82:1–145, 2020; BMJ Case Rep Dec 2011

Arthro-ophthalmopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.532–533 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Syndrome Ident 8:6–9, 1982

Bart-Pumphrey syndrome – autosomal dominant; connexin 26 mutation; diffuse honeycomb palmoplantar keratoderma, sensorineural deafness, knuckle pads, leukonychia Clinics in Dermatol 23:23–32, 2005; Curr Prob Derm 14:71–116, 2002; NEJM 276:202– 207, 1967

METABOLIC DISEASES Mannosidosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.130–131Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987

Hypohidrotic ectodermal dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.456–457Vitiligo – cochlear dysfunction BJD 172:406–411, 2015

Alport’s syndrome – gouty tophi, nephritis, deafness

Bardet-Biedl Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.288–289

Zika virus – transient unilateral hearing loss in acute Zika infection Clin Inf Dis 64:675–677, 2017

PRIMARY CUTANEOUS DISEASES

Alopecia-onychodysplasia-hypohidrosis-deafness syndrome – small teeth, thick dystrophic toenails, hypohidrosis, hyperkeratosis of palms and soles, elbows and knees, sensorineural deafness Human Hered 27:127–337, 1977

Bazex-Dupre-Christol syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Ped Derm 25:112–113, 2008; Ped Derm 23:286–290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Begeer syndrome – cataracts, deafness, short stature, ataxia, polyneuropathy Clin Dysmorphol 4:283–288, 1995 Bilateral defects, male transmission – bilateral cervical branchial sinuses, bilateral preauricular sinuses, bilateral malformed auricles, bilateral hearing impairment Hum Genet 56:269–273, 1981 Bjornstad syndrome – autosomal recessive; sensorineural hearing loss, pili torti (short coarse spangled hair with breakage); BCS1L gene mutation (ATPase activity) BJD 170:970–973, 2014; Ped Derm 30:674–682, 2013; Eur J Dermatol 10:91–97, 2000

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Blacklock’s albinism deafness syndrome (BADS) Branchio-otic syndrome – autosomal dominant; branchial anomalies, preauricular pits, hearing loss, no renal dysplasia J Med Genet 39:71–73, 2002 Branchio-oto-renal syndrome (BOR) – autosomal dominant; mutation in EYA1 gene; conductive, sensorineural, mixed hearing loss; pre-auricular pits, structural defects of outer, middle, or inner ear; renal anomalies, renal failure, lateral cervical fistulae, cysts, or sinuses; nasolacrimal duct stenosis or fistulae Am J Kidney Dis 37:505–509, 2001; Cutis 68:353–354, 2001 CINCA syndrome (chronic infantile neurologic cutaneous articular syndrome) NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA chronic infantile neurological cutaneous and articular syndrome) – urticarial lesions at birth, chronic meningitis, arthralgias of knees and ankles with deforming arthropathy with epiphyseal bone formation, deafness, hepatosplenomegaly, uveitis, vitreitis, papilledema, corneal stromal keratopathy; frontal bossing; angelic facies, mental retardation; sensorineural hearing loss, fever and rash more severe in evening; mutation in NALP3 (CIAS 1) which encodes cryopyrin AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319– 321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005; Eur J Pediatr 156:624–626, 1997; chronic urticaria AD 136:431–433, 2000; J Pediatr 99:79–83, 1981 Cleft palate and sensorineural hearing loss Helv Paediatr Acta 38:267–280, 1983 Clouston’s syndrome – mild sensorineural hearing loss, alopecia, thick dystrophic nail plates, palmoplantar keratoderma, photophobia; mutation in GJB2 and GJB6 (connexin 30) JAMA Derm 149:1350–1351, 2013 Cockayne syndrome – xerosis with rough, dry skin, anhidrosis, erythema of hands, hypogonadism; autosomal recessive; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects including retinal degeneration, demyelination JAAD 75:873–882, 2016; JAMA Derm 149:1414–1418, 2013; Ped Derm 20:538–540, 2003; Am J Hum Genet 50:677– 689, 1992; J Med Genet 18:288–293, 1981; bird-headed dwarfism Congenital cataracts, sensorineural deafness, hypogonadism, hypertrichosis, short stature Clin Dysmorphol 4:283–288, 1995 Congenital keratosis palmaris et plantaris-deafness-leukonychia totalis syndrome Indian J Dermatol Venereol Leprol 78:107–108, 2012 Cowden’s syndrome Craniometaphyseal dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.104 Craniosynostosis, anal anomalies, and porokeratosis (CAP/ CDAGS) – autosomal recessive; craniosynostosis, clavicular hypoplasia, delayed fontanel closure, cranial defects (parietal foramina), deafness, imperforate anus or anterior placement of anus, genitourinary abnormalities (hypospadias and urethrorectal fistula), and skin eruption (porokeratosis-­like lesions), mental retardation, scant hair, Staphylococcus aureus infections JAAD 68:881–884, 2013; Am J Hum Genet 77:161–168, 2005; J Med Genet 35:763–766, 1998 Crouzon syndrome II Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.12–13

Cytoplasmic body and mitochondrial DNA deletion – marfanoid habitus and perceptive hearing loss J Neurol Sci 99:291–300, 1990 Deafness, pre-auricular sinus, external ear anomaly, and commissural lip pit syndrome – autosomal dominant; pinna dysplasia, mixed or conductive hearing loss Cutis 88:275–278–280, 2012; Laryngoscope 76:1277–1288, 1966; Br Med J ii:1354–1356, 1955 Deafness and lentigines Deafness, vitiligo, and muscle wasting of hands, feet, and legs Arch Otolaryngol 93:194–197, 1971 Deletion of short arm of chromosome 4 (4p (-) syndrome) – mental retardation, deafness, seizures, ocular abnormalities Duane anomaly – familial and urogenital abnormalities with bisatellited marker derived from chromosome 22 – Duane retraction syndrome – congenital cranial dysinnervation disorder with paradoxical lateral rectus muscle innervation of the affected eye by aons meant to innervate the ipsilateral medial rectus muscle (resultant varying degrees of cocontraction); sensorineural deafness and preauricular skin tags Am J Med Genet 47:925–930, 1993 Dwarfism-alopecia-pseudoanodontia- cutis laxa – autosomal recessive; generalized atrichia, unerupted teeth, hyperconvex nails, cutis laxa with fragile skin, dwarfism, deafness, eye anomalies Cien Cult 34 (Suppl): 705, 1982 Dyschromatosis universalis hereditaria – mottled hyperpigmentation, small stature, high tone deafness Ped Derm 24:566–570, 2007; Semin Cut Med Surg 16:72–80, 1997; Clin Exp Derm 2:45, 1977 Ectodermal dysplasia with cataracts and hearing defects (Marshall’s syndrome) – dental defects, cataracts, deafness Am J Ophthalmol 45:143–156, 1958 Ectrodactyly, ectodermal dysplasia, cleft lip and palate syndrome (EEC syndrome) – fine, dry, wiry hypopigmented sparse hair and eyelashes, scarring alopecia, mental retardation; alopecia of scalp, eyebrows, and eyelashes, xerosis, atopic dermatitis, nail dystrophy, hypodontia with peg shaped teeth, reduced sweat glands and salivary glands, syndactyly, mammary gland and nipple hypoplasia, conductive or sensorineural hearing loss, urogenital anomalies, lacrimal duct abnormalities; TP63 mutations BJD 162:201–207, 2010; Ped Derm 20:113–118, 2003; BJD 146:216–220, 2002; Clin Dysmorphol 5:115–127, 1996; Dermatologica 169:80–85, 1984Clin Genet 9:35–40, 1976 Fabry’s disease – tinnitus, deafness JAAD 74:231–244, 2016 Fanconi’s anemia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.440–441 Fisch’s syndrome – early hypopigmented hair, poliosis; impaired hearing; partial heterochromia iridis Clin Genetics 60:301–394, 2001; J Med Genet 3:656–665, 1997 Flynn-Aird syndrome – progressive sensorineural deafness is the first feature, neurologic signs and symptoms, sclerodermoid changes, bony changes Focal palmoplantar keratoderma and sensorineural deafness BJD 143:876–883, 2000 GATA 2 deficiency – multiple warts, multiple soft tissue infections, lower leg lymphedema, sensorineural deafness, squamous cell carcinomas, panniculitis, erythema nodosum, Sweet’s syndrome; GATA 2 – zinc finger transcription factor that regulates vascular and lymphatic development, and hematopoietic maturation JAAD 73:367–381, 2015; JAAD 71:577–580, 2014 GM1-gangliosidosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.132–133 GM2-gangliosidoses Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.116–117

Deafness or Hearing Impairment, Cutaneous Manifestations Gingival fibromatosis with sensorineural hearing loss (Jones) Ped Derm 18:534–536, 2001; Am J Med Genet 22:623–627, 1985 Goldenhar syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.52–53 H syndrome – autosomal recessive; facial telangiectasias; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, short stature, facial telangiectasia, gynecomastia, camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azoospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly; Arabic Palestinian population; gluteal lipoatrophy; hyperpigmentation, hearing loss, diabetes mellitus, lymphadenopathy, hypertrichosis, heart anomalies, micropenis, hallus valgus, hyperpigmentation induration and hypertrichosis of inner thighs and shins (sclerodermoid), chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 Ped Derm 32:731–732, 2015; JAAD 70;80– 88, 2014;JAAD 59:79–85, 2008 Hajdu-Cheney syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.432–433 Hearing loss with atopic dermatitis (familial) – atopic dermatitis-like eruption Acta Otolaryngol 82:242, 1976 Hemifacial microsomia syndrome – bilateral preauricular sinuses, facial steatocystoma multiplex associated with pilar cysts, sensorineural hearing loss, facial palsy, microtia or anotia, cervical appendages containing cartilage Am J Med Genet 22:135–141, 1985 Hereditary diffuse PPK with progressive neurosensory deafness AD 118:605–607, 1982; J Laryngol Otol 89:1143–1146, 1975 HID syndrome (hystrix-like ichthyosis with deafness) – autosomal dominant; shark-skin appearance, sensorineural deafness, spiky and cobblestoned hyperkeratosis, neonatal erythroderma, scarring alopecia, occasional punctate keratitis; probably variant of KID syndrome with mutation of connexin 26 (gap junction protein) BJD 146:938–942, 2002 Hirshowitz (Groll-Hirshowitz) syndrome – nerve deafness, peripheral sensory demyelinization, loss of gastric motility, ileal and jejunal diverticulae with ulcers JAAD 57:502–508, 2007; Clin Genet 28:76–78, 1985 Hunter’s syndrome (mucopolysaccharidosis IIb) – X-linked recessive; MPS type II; iduronate-2 sulfatase deficiency; lysosomal accumulation of heparin sulfate and dermatan sulfate; linear and reticulated 2–10mm skin colored papules over and between scapulae, chest, neck, arms; also posterior axillary lines, upper arms, forearms, chest, outer thighs; rough thickened skin, coarse scalp hair, and hirsutism; short stature, full lips, coarse facies with frontal bossing, hypertelorism, and thick tongue (macroglossia); dysostosis multiplex; hunched shoulders and characteristic posturing; widely spaced teeth, dolichocephaly, deafness, retinal degeneration, inguinal and umbilical hernias hepatosplenomegaly; upper and lower respiratory infections due to laryngeal or tracheal stenosis; mental retardation; deafness; retinal degeneration and corneal clouding; umbilical and inguinal hernias; valvular and ischemic heart disease with thickened heart valves lead to congestive heart failure; clear corneas (unlike Hurler’s syndrome), progressive neurodegeneration, communicating hydrocephalus; adenotonsillar hypertrophy, otitis media, obstructive sleep apnea, diarrhea Ped Derm 21:679–681, 2004; Clin Exp Dermatol 24:179– 182, 1999; Ped Derm 7:150–152, 1990 Hurler’s syndrome (mucopolysaccharidosis type I-H) – disorder of glycosaminoglycans accumulation; autosomal recessive; coarse

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facies, macroglossia, short stature, macrocephaly, hepatosplenomegaly, hernias, corneal clouding, vision and hearing loss; cardiac anomalies; respiratory infections; alpha-l-iduronate deficiency Ped Derm 33:594–601, 2016; Hypodontia, sensorineural hearing loss and dizziness Arch Otolaryngol 104:292–293, 1978 Infantile hemangiomas – within the parotid gland; conductive hearing loss Sem Cut Med Surg 35:108–116, 2016 Johanson-Blizzard syndrome – autosomal recessive; growth retardation, microcephaly, ACC of scalp, sparse hair, hypoplastic ala nasi, CALMs, hypoplastic nipples and areolae, hypothyroidism, sensorineural deafness Clin Genet 14:247–250, 1978 Johnson-McMillin syndrome – autosomal dominant, facial nerve palsy, hearing loss, hyposmia, hypogonadism, microtia, alopecia Kearns-Sayre syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.500–501 Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, follicular occlusion triad, scalp cysts, nodules (trichilemmal tumors, squamous cell carcinoma), bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation Dermatol Ther 28:89–93, 2015; JAAD 69:127–134, 2013; Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; JAAD 19:1124– 1126, 1988; AD 123:777–782, 1987; Ped Derm 2:1–7, 1984; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915 Keutel syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.230–231 Klippel-Feil syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.296–297 Kniest syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.250–261 Knuckle pads-leukonychia-deafness syndrome leukonychia totalis Ped Derm 31:404–405, 2014 Lacrimo-auriculo-dento-digital (LADD) syndrome – cup-shaped ears, hearing loss, nasolacrimal duct obstruction, hypodontia, enamel dysplasia, digital malformations Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.378–379; Eur J Pediatr 146:536–537, 1987; J Med Genet 24:94–95, 1987; J Pediatr 83:438–444, 1973 Langer-Gideon syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.408–409 LEOPARD syndrome (multiple lentigines syndrome; Moynahan syndrome) – autosomal dominant; generalized lentiginosis, especially over neck and trunk; structural cardiac abnormalities, cardiac symptoms, electrocardiographic abnormalities, genitourinary abnormalities (gonadal hypoplasia, hypospadias, delayed puberty), neurologic defects, cephalofacial dysmorphism, short stature or low birth weight, skeletal abnormalities; deafness; mutation in PTPN11 BJD 161:1202–1204, 2009; Ped Derm 21:139–145, 2004; JAAD 46:161–183, 2002; J Med Genet 34:582–586, 1997; Am J Dis Child 117:652–662, 1969; café noir spots Ped Derm 25:444–448, 2008 Leukonychia, deafness, enamel dysplasia Genetic Skin Disorders, Second Edition, 2010, pp.239

246 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Lip pits – preauricular sinuses, conductive deafness, commissural lip pits, external ear abnormalities J Med Genet 24:609–612, 1987; preauricular pits, commissural lip pits, congenital conductive/mixed deafness Ann Otol Rhinol Laryngol 100:928–932, 1991 Maroteaux-Lamy syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.126–127 MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes; central nervous system abnormalities, neurosensory hearing loss, dermatomyositis, cardiomyopathy JAAD 65:473–491, 2011 Melnick-Needles syndrome II Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.30–31 Mental retardation-enteropathy-deafness-neuropathy-ichthyosis-­­ keratodermia syndrome JAAD 63:607–641, 2010; Proc Natl Acad Sci USA 4:1–9, 2009 Michelin tire baby syndrome – either nevus lipomatosis or diffuse smooth muscle hamartoma; degenerative collagen, scarring; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques; low set malformed ears with thickened helix and anti-helix; wide or depressed nasal bridge; epicanthal folds, hypertelorism, cleft palate, micro-ophthalmia or deep set eyes, flat or hypoplastic midface, short neck, decreased hearing, hypoplastic malformed genitalia, micrognathia, histologically increased periadnexal fat and subcutaneous fat and smooth muscle hamartomas; mental retardation, tendinous hyperlaxity, seizures, mastocytosis, complex malformations syndrome (bilateral calcaneovalgus deformity, cleft palate, inguinal hernia, hip deformity, clefting of lateral mouth commissures, shawl scrotum, absent foreskin; developmental delay, microcephaly, mental retardation Ped Derm 31:659–663, 2014JAAD 63:1110– 1111, 2010; Ped Derm 27:79–81, 2010; Ped Derm 24:628–231, 2007; Ped Derm 22:245–249, 2005; Ped Derm 20:150–152, 2003; BJD 129:60–68,1993; JAAD 28:364–370, 1993; Ped Derm 6:329–331, 1989; Am J Med Genet 28:225–226, 1987; AD 115:978–979, 1979; diffuse lipomatous hypertrophy AD 100:320– 323, 1969; generalized muscular nevus Ann DV 107:923–927, 1980 Mobius sequence Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.49–493 Morquio’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.124–125 Muckle-Wells syndrome – autosomal dominant; macular erythema (evanescent red macules), urticaria (cold air urticaria) lesions lasting 1–2 days, deafness, extremity pain, arthralgias of knees and ankles with arthritis; progressive sensorineural hearing loss; nephropathy, AA amyloidosis with neuropathy; fever and rash more severe in evening; mutation in gene encoding CIAS, NALP3 (cryopyrin) JAAD 68:834–853, 2013; AD 144:392–402, 2008; AD 142:1591–1597, 2006; BJD 151:99–104, 2004; JAAD 39:290–291, 1998; BJD 100:87–92, 1979; QJMed 31:235–248, 1962 Myotonic dystrophy (Steinert syndrome) type 1 – autosomal dominant; muscular hypotonia, distal weakness of muscles, frontal alopecia, cataract, sensorineural hearing loss, dysarthria, dysphagia, diabetes mellitus, hypothyroidism, cardiac arrhythmias Dtsch Arztebl Int 116:489–496, 2019; J Med Genet 19:341–348, 1982 Premature aging syndrome (Mulvihill-Smith syndrome) – premature aging and immunodeficiency; multiple congenital melanocytic nevi, freckles, blue nevi, lack of facial subcutaneous tissue, xerosis, telangiectasias, thin skin, fine silky hair, premature aging, low birth weight, short stature, birdlike facies, hypodontia, high-pitched voice, mental retardation, sensorineural hearing loss, hepatomegaly Am J Med Genet 69:56–64, 1997; J Med Genet 31:707–711, 1994; Am J Med Genet 45:597–600, 1993

Myhre syndrome – low birth weight, short stature, muscular build, limited joint mobility, cardiac defects, deafness, skeletal abnormalities, facial dysmorphism, thick skin, keratosis pilaris, coarse facies Nager acrofacial dysostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.50–51 Nerve deafness, eye anomalies, and Marfanoid habitus – autosomal dominant Birth Defects: Original Article Series.07(4):137–139, 1971 Neutral lipid storage disease (Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma (non-bullous congenital ichthyosiform erythroderma and neutral lipid storage disease); thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness; ABHD5 mutation; a necessary cofactor for adipose triglyceride lipase-mediated lipolysis; AD 141:798–800, 2005; Am J Dermatopathol 20:79–85, 1998; JAAD 17:801–808, 1987; AD 121:1000–1008, 1985 hyperkeratosis of the knees; hepatomegaly, ataxia, neurosensory hearing loss, cataracts, nystagmus, short stature, leukocytes with lipid vacuoles BJD 158:1378–1380, 2008 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA chronic infantile neurological cutaneous and articular syndrome) – cryopyrinopathy with mutation in CIAS1 (encodes cryopyrin); edematous papules and plaques, urticarial-like lesions in newborn, lesions, chronic aseptic meningitis, arthralgias of knees and ankles with disabling deforming arthropathy with epiphyseal bone formation (osseous overgrowth), deafness, hepatosplenomegaly, anterior uveitis, vitreitis, papilledema, corneal stromal keratopathy; blindness, mental retardation; high frequency hearing loss, developmental delay; recurrent fever and rash more severe in evening; headache, macrocephaly, cerebral atrophy; mutation in NALP3 (CIAS 1) which encodes cryopyrin JAAD 68:834–853, 2013; AD 144:392–402, 2008; AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319–321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005 Noonan’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.196–197 Oculo-cerebral hypopigmentation syndrome of Preus – very short with thin build, ptosis, high arched palate, dental malocclusion, prominent central upper incisors, hair and skin hypopigmented, deafness, severe mental retardation Ped Derm 24:313–315, 2007 Orofaciodigital syndrome type II Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.416–417 Osteogenesis imperfecta Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.368–369 Oto-palatal-digital syndrome II Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.26–27 Palmoplantar keratoderma with deafness SKINmed 12:107–108, 2014; BJD 134:939–942, 1996; Dermalogica 175:148–151, 1987; A7445G point mutation in mitochondrial genome BJD 143:876–883, 2000; connexin mutations J Med Genet 37:50–51, 2000; Eur J Hum Genet 8:469–472, 2000 Palmoplantar keratoderma, pseudoainhum (constriction bands), knuckle pads, hearing loss – mutation in GJB6 encoding connexin 30 BJD 161:452–455, 2009 Papillon-Lefevre syndrome SKINmed 12:107–109, 2014 Perioral cobblestoning, ichthyosis and deafness AD 124: 102–106, 1988

Deafness or Hearing Impairment, Cutaneous Manifestations Perrault syndrome – gonadal dysgenesis, progressive sensorineural deafness, marfanoid body proportions and skeletal features; normal female karyotype PGM3 deficiency – autosomal recessive; dermatitis, conductive hearing loss, ataxia, myoclonus, narrow palpebral fissures; increased IgE; herpes simplex, molluscum contagiosum viral infections, sinopulmonary infections, chronic mucocutaneous candidiasis, developmental delay JAAD 73:355–364, 2015 PHACES syndrome – hearing loss Sem Cut Med Surg 35:108–116, 2016; Ped Derm 31:290–292, 2014 Phylloid hypermelanosis – cicatricial alopecia, onychodystrophy, deafness, malformed ear, mental retardation, umbilicated nipples JAAD 19:1037–1044, 1988; Rev Neurol (Paris) 95:48–54, 1956 Pili torti – autosomal recessive, autosomal dominant, sporadic; isolated defect hair that won’t grow long Cutis 84:143–147, 2009; JAAD 59:1–22, 2008; JAAD 53:S130–134, 2005; Acta DV 53:385–392, 1973; Arch Dermatol Syphilol 26:98–109, 1932; associated with Menkes’ kinky hair syndrome – X-linked recessive; early growth retardation, abnormal hair, focal cerebral and cerebellar degeneration Ann DV 102:269–271, 1980; Pediatrics 50:181–183, 1972; Pediatrics 29:764–779, 1962; Beare syndrome – late onset pili torti with black scalp hair, sparse body and beard hair, patchy alopecia after puberty BJD 64:366–372, 1952; Bjornstad’s syndrome – autosomal recessive, autosomal dominant; congenital sensorineural hearing loss Eur J Dermatol 10:91–97, 2000; Bazex syndrome, Crandall’s syndrome – congenital sensorineural hearing loss and hypogonadism, hidrotic ectodermal dysplasia, pseudomonilethrix, oral retinoids Cutis 35:466–470, 1985; Rapp-Hodgkin syndrome – autosomal dominant, sporadic; anhidrotic ectodermal dysplasia, cleft lip, palate, pili torti, hypodontia, abnormal fingernails, hypospadias J Med Genet 5:269–272, 1968; trichodysplasia-xeroderma – autosomal dominant; xerosis, abnormal hair (alopecia, pili torti, trichorrhexis nodosa) Clin Genet 31:337–342, 1987; trichothiodystrophy – autosomal recessive AD 116:1375–1384, 1980; Ronchese variants – autosomal recessive, autosomal dominant, sporadic; early onset pili torti; leukonychia, dental abnormalities, keratosis pilaris, dystrophic nails, ichthyosis Arch Dermatol Syphilol 26:98–109, 1932; anorexia nervosa Cutis 57:151–152, 1996; with cleft lip and palate, malformed ears, syndactyly, and mental retardation J Med Genet 25:37–40, 1988; in Rapp-Hodgkin syndrome Oral Surg Oral Med Oral Pathol 67:50–62, 1989; anorexia nervosa Cutis 57:151–152, 1996; monilethrix, woolly hair, mitochondrial disorders, Netherton’s syndrome, Bazex syndrome, longitudinal grooves, trichorrhexis nodosa, citrullinemia, Laron syndrome Ectodermal dysplasias associated with pili torti include:   Widely spaced teeth and enamel hypoplasia   Acrofacial dysostosis of the palagonia type   Tooth agenesis  Arthrogryphosis   Nail dystrophy Dermatologica 182:184–187, 1991  Clefting   Corneal opacities   Trichodysplasia xeroderma   Hypohidrotic ectodermal dysplasia  Ichthyosis Poliosis – deafness, unilateral tapetoretinal degeneration Porokeratotic eccrine ostial and dermal duct nevus – resemble nevus comedonicus; linear keratotic papules with central plugged pit; may be verrucous; filiform; anhidrotic or hyperhidrotic; most common on palms and soles JAAD 43:364–367, 2000; JAAD 24:300–1, 1991; Cutis 46:495–497, 1990; generalized porokeratotic eccrine ostial and dermal duct nevus – blaschko-distributed

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verrucous plaques; non-scarring alopecia, hypohidrosis, teeth in disarray, deafness JAAD 59:S43–45, 2008 Progressive diaphyseal dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.520–521 Primrose syndrome – enlarge calcified ears; distal muscle wasting, diabetes, deafness, basal ganglia calcification Mol Syndromol 9:70–82, 2018 Refsum syndrome – autosomal recessive; ichthyosis, ataxia, peripheral neuropathy, increased CSF protein, retinitis pigmentosa, anosmia, progressive sensorineural hearing loss, cardiac arrhythmias, AV conduction impairment, elevated phytanic acid Rubella embryopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.528–529 San Filippo syndrome (A–D) – autosomal recessive; accumulation of glycosaminoglycans; decreased hearing, skeletal deformities Ped Derm 33:594–601, 2016 Sensorineural hearing loss, periorificial erythrokeratoderma, dental enamel defects, excess granulation tissue JID 121:1221–1223, 2003 Spondyloepiphyseal dysplasia congenita Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.246–247 Stickler syndrome (hereditary arthro-ophthalmopathy) WagnerStickler syndrome (dystrophia vitreoretinal is hereditaria) – autosomal dominant; flat midface, cleft palate, myopia with retinal detachment, cataracts, hearing loss, arthropathy Clinics in Dermatol 24:521–533, 2006; J Med Genet 36:353, 359, 1999; Birth Defects 11:77–103, 1975 Symphalangism-brachydactyly syndrome – conductive hearing impairment Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.424–425 Tietz’s syndrome – autosomal dominant; generalized absence of pigment and hypopigmented patches of skin; congenital deaf-mutism, hypoplastic eyebrows; canities JAAD 69:625–633, 2013; Am J Hum Genet 15:259–264, 1963 Townes-Brocks syndrome – preaxial polydactyly, external ear abnormalities, hearing loss, imperforate anus, renal malformations; autosomal dominant; chromosome 16q12.1 Cutis 77:365–366, 2006 Treacher Collins syndrome (mandibulofacial dysostosis) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.48–49 Triphalangeal thumbs-onychodystrophy-deafness syndrome (triphalangism of the first ray) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.434–435 Trisomy 13 – total body milia; polydactyly, congenital cystic adenomatoid malformation, pulmonary hypertension, apnea, atrial septal defect, umbilical hernia, epilepsy, dislocated hip joint, ocular hypertelorism, microphthalmia, retinal hypoplasia, irideremia, small ears, deafness, broad flat nose, cleft palate, micrognathia, mental retardation Ped Derm 27:657–658, 2010 Turner’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.192–193 Universal dyschromatosis with photosensitivity and neurosensory hearing defect AD 126:1659–1660, 1990 Vogt-Koyanagi-Harada syndrome – occurs primarily in Asians, blacks, and darkly pigmented Causians; Stage 1 – aseptic meningitis; Stage 2 – uveitis (iritis, iridocyclitis) and dysacusis (tinnitus, hearing loss); Stage 3 – depigmentation of skin (60% of patients), depigmentation of hair (poliosis – eyelashes, eyebrows, scalp, and body hair – 90% of patients), alopecia areata; halo nevi Ann DV 127:282–284, 2000; AD 88:146–149, 1980; alopecia, dysacusia, poliosis, uveitis, vitiligo JAAD 44:129–131, 2001; Neurology 20:965–974, 1970

248 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Vohwinkel’s syndrome (keratoderma hereditaria mutilans) – autosomal dominant; honeycomb palmoplantar keratoderma, hyperkeratotic knuckle papules with starfish keratoses; ichthyosis, pseudoainhum; JAAD 44:376–378, 2001; with congenital sensorineural deafness – mutation in GJB2 (connexin 26) (gap junction protein), D66H; or loricrin mutations BJD 164:197–199, 2011; Clinics in Dermatol 23:23–32, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 44:376–378, 2001; BJD 145:657–660, 2001; Hum Mol Genet 8:1237–1243, 1999; loricrin mutation JID 111:702–704, 1998; Nat Genet 13:70–77, 1996 Waardenburg’s Syndrome – autosomal dominant, congenital deafness, heterochromic irides, hypomelanotic macule, lateral displacement of the inner canthi and lacrimal punctae, prominence of nasal root and medial eyebrows, white forelock AD 135:859–861, 1999 Waardenberg’s syndrome – type I – white forelock; dystopia canthorum, broad nasal root, synophrys, iris heterochromia, deafness, canities, piebaldism; hypoplasia of nasal alae, terminal hair on tip of nose; PAX 3 gene mutation; type II – sensorineural hearing loss, heterochromic irides, absence of dystopia canthorum; MITF mutations; type III (Waardenbug-­Klein syndrome) – features of type I, limb abnormalities; PAX 3 gene mutations; type IV (Waardenburg-Shah syndrome) – extensive depigmentation; Hirschsprung’s disease; endothelin receptor B gene mutations NEJM 360:160–169, 2009; Dermatol Clin 6:205–216, 1988 Whistling face syndrome II Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.46–47 Wildervanck syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.298–299 Woodhouse-Sakati syndrome – autosomal recessive; triangular shaped face with prominent forehead, large low set ears, dystonia, ­hypotrichosis, with sparse eyebrows and eyelashes; alopecia, hypogonadism, diabetes mellitus, mental retardation, sensorineural deafness, extrapyramidal signs, low insulin-like growth factor 1; must be differentiated from congenital hypotrichosis; mutation in C2orf37 Ped Derm 31:83–87, 2014; Am J Med Genet 143:149–160, 2007; J Med Genet 20:216–219, 1983 Woolf syndrome – autosomal recessive; piebaldism with congenital nerve deafness JAAD 48:466–468, 2003; Arch Otolaryngol 82:244–250, 1965 Xeroderma pigmentosum – sensorineural deafness JAAD 75:855– 870, 2016 Ziprkowski-Margolis syndrome – X-linked recessive, deaf-mutism, heterochromic irides, piebald-like hypomelanosis, hyperpigmented macules with geographic appearance Cutis 80:411–414, 2007; JAAD 48:466–468, 2003

VASCULAR DISORDERS PHACES – hearing loss in adults Ped Derm 36:618–622, 2019

Allergic contact dermatitis – numerous allergens; systemic contact dermatitis to foods – flexural dermatitis, eyelid, genital, dyshidrosis Cutis 104:337–340, 2019; plantar foot dermatitis due to dialkylurea Ped Derm 36:514–516, 2019 Anti-synthetase syndrome – mechanics’ hands, Raynaud’s phenomenon, interstitial lung disease, anti-Jo-1 antibody AD 141:779–784, 2005 Severe atopic dermatitis, elevated IgE levels, and recurrent infections Dermatol Clin 35:11–19, 2017   DOCK8 syndrome   Hyper IgE syndrome (Job’s syndrome)  Omenn syndrome – severe combined immunodeficiency; severe erythroderma, infections, lymphadenopathy, hepatosplenomegaly  Phosphoglucomutase 3 (PGM3) deficiency – atopy and hypergammaglobulinemia, developmental delay  STK4 or Macrophage-Stimulating 1 (MST1) deficiency – cutaneous viral, bacterial, fungal infections; respiratory infections, cardiac anomalies   Tyk2 deficiency  Wiskott-Aldrich syndrome – X-linked recessive; T-cell lymphopenia, autoimmunity, malignancy recurrent bacterial and viral infections, vascular abnormalities, microthrombocytopenia Autoimmune estrogen dermatitis JAAD 32:25–31, 1995 Autoimmune progesterone dermatitis Acta DV 69:308–310, 1989 Bare lymphocyte syndrome Bruton’s hypogammaglobulinemia – atopic-like dermatitis; dermatomyositis-­like syndrome Bullous pemphigoid – dermatitis lesions JAAD 81:355:363, 2019; JAMA Derm 149:950–953, 2013; JAAD 29:293–299, 1993; subacute prurigo variant JAAD 47:133–136, 2002; early signs of bullous pemphigoid – urticarial lesions, dermatitis, excoriations BJD 167:1111–1117, 2012; C3 deficiency – recurrent infections, vasculitis, LE; C3 inactivator deficiency – dermatitis early in infancy Cell-associated glycoprotein deficiency Chronic granulomatous disease – seborrheic dermatitis-like changes, X-linked or autosomal recessive, Xp21 (distal end of Xp), localized pyodermas, abscesses, granulomas, perioral and intraoral ulcers, lungs/liver/spleen, defect in NADPH oxidase system; including NADPH, phagocyte cytochrome b, and cytosolic proteins; membrane-associate NADPH oxidase system fails to produce superoxide and other toxic oxygen metabolites; Staphylococcus aureus, Klebsiella, Pseudomonas, Escherichia coli, Serratia, Aspergillus, Candida, Cryptococcus, Nocardia Cicatricial pemphigoid Common variable immunodeficiency BJD 178:335–349, 2018 Dermatitis herpetiformis – dermatitis with or without lichenification Rook p. 1890, Sixth Edition Dermatomyositis – personal observation

DERMATITIS (SPONGIOTIC DERMATITIS), DIFFERENTIAL DIAGNOSIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Agammaglobulinemia Curr Prob in Derm 10:41–92, 1998; J Allergy 33:406–411, 1962; X-linked hypogammaglobulinemia (agammaglobulinemia) J Allergy 33:406–411, 1962

DiGeorge’s syndrome (congenital thymic aplasia) – autosomal dominant or sporadic; seborrheic dermatitis, atopic dermatitis; developmental defects of 3rd and 4th pharyngeal pouches, congenital thymic aplasia, neonatal tetany due to absence of parathyroids, cardiac anomalies (truncus arteriosus), short philtrum, low-set malformed ears, hypertelorism, increased susceptibility to Candida, viral, and Pneumocystis carinii infections, loss of portion of proximal long arm of chromosome 22, may be same as velocardiofacial syndrome DOCK8 deficiency syndrome (dedicator of cytokinesis 8 gene) (aka autosomal recessive hyper-IgE syndrome) DOCK8 – autosomal recessive; involved in T cell polarization and activation; atypical guanine exchange factor; interacts with Rho GTPases (CDC42 AND

Dermatitis (Spongiotic Dermatitis), Differential Diagnosis RAC) which mediate actin cytoskeletal reorganization; hematologic stem cell homing and mobilization – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE with multiple allergies, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; herpes simplex, warts, molluscum contagiosum – red papules of neck; widespread dermatitis (atopic dermatitis-like (24% at birth; Job’s 81% dermatitis at birth), food and environmental allergies; 50% with asthma, cutaneous staphylococcal abscesses; sinopulmonary infections; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; cutaneous T-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation BJD 178:335–349, 2018; JAAD 73:355–364, 2015; AD 148:79–84, 2012 Fogo selvagem Graft vs. host disease, chronic – lichenoid dermatitis AD 119:683– 689, 1983; eczematoid graft vs. host disease Ped Derm 35:343– 353, 2018; AD 143:1157–1162, 2007; Ann DV 126:51–53, 1999; J Clin Pathol 37:919–930, 1984; atopic dermatitis-like JAAD 69:34–39, 2013 Hyper-IgE syndrome (Job’s syndrome) –  Autosomal dominant; dermatitis, cold abscesses, skeletal and connective tissue abnormalities; mutation in STAT3 (signal transducer and activator of transcription 3); neonatal papulopustular eruption begins on face and scalp, spreads to generalized distribution; recurrent sinopulmonary infections, chronic mucocutaneous candidiasis; characteristic facies including large bulbous nose, prominent chin, prominent pores, craniosynostosis, Chiari 1 malformation, retained primary teeth, high arched palate, scoliosis, joint hyperextensibility; vascular anomalies including lacunar brain infarcts, coronary aneurysms and tortuosity; increased risk of non-Hodgkin’s lymphoma; high IgE but no increased incidence of allergies JAAD 73:355–364, 2015; also mutation in phosphoglucomutase-3 (PGM3); mutations in tyrosine kinase 2 BJD 178:335–349, 2018; JAAD 73:355–364, 2015; Ped Derm 28:494–501, 2011; Curr Opin Allergy Clin Immunol 7:506–509, 2007; Immunity 25:745–755, 2006 X-linked immunodeficiency with hyper-IgM – atopic dermatitis-like rash Immunologic amnesia syndrome NEJM 281:285–290, 1969 Infant car seat dermatitis – elbows, lower lateral legs, occiput Ped Derm 28:321–326, 2011 IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, pemphigoid nodularis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash; thyroid dysfunction, diabetes mellitus, hepatitis, nephritis, onychodystrophy, alopecia universalis; mutations in FOXP3 (forkhead box protein 3) gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia BJD 178:335–349, 2018; JAAD 73:355–364, 2015; BJD 160:645–651, 2009; ichthyosiform eruptions Blood 109:383–385, 2007; BJD 152:409–417, 2005; NEJM 344:1758–1762, 2001; alopecia areata AD 140:466–472, 2004 Jung’s syndrome (antihistamine responsive immunodeficiency) – atopic dermatitis, pyoderma, folliculitis, blepharitis with defective leukocyte and lymphocyte function Am J Med Genet 66:378–398, 1996; Lancet ii:185–187, 1983

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Leiner’s disease Linear IgA dermatosis Lupus erythematosus – with or without vasculitis Mammalian sterile 20-like kinase 1 deficiency (MST1 deficiency) – autosomal recessive; dermatitis; bacterial, viral, candidal infections; structural cardiac anomalies including atrial septal defect, patent foramen ovale, valvular disease JAAD 73:355–364, 2015 Pemphigoid gestations – personal observation Pemphigus foliaceus – starts in seborrheic distribution (scalp, face, chest, upper back) Mil Med 184:e455–457, 2019; AD 83:52–70, 1961 Pemphigus vulgaris – adult facial dermatitis; personal observation PGM3 deficiency – autosomal recessive; dermatitis, conductive hearing loss, ataxia, myoclonus, narrow palpebral fissures; increased IgE; herpes simplex, molluscum contagiosum viral infections, sinopulmonary infections, chronic mucocutaneous candidiasis, developmental delay BJD 178:335–349, 2018; JAAD 73:355–364, 2015 PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAAD 73:355–364, 2015; JAMA Derm 151:627–634, 2015 Rheumatoid neutrophilic dermatitis J Cut Pathol 19:48–53, 1992 SAM syndrome – severe dermatitis, allergies, metabolic wasting; palmoplantar keratodermas Ped Derm 37:576–578, 2020; BJD 179:755–757, 2018; BJD 172:257–261, 2015 Selective IgA deficiency BJD 178:335–349, 2018; Curr Prob in Derm 10:41–92, 1998 Selective IgM deficiency Severe combined immunodeficiency syndrome – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks); erythroderma, seborrheic dermatitis-like eruption; morbilliform eruptions, lichen planus-like eruptions, dermatitis; dermatitis and alopecia; mutations in cytokine common gamma chain, JAK3, RAG1 or RAG2, IL-7Rgamma, adenosine deaminase JAAD 66:292–311, 2012; Ped Derm 26:213–214, 2009; AD 144:342–346, 2008; Dermatol Therapy 18:176–183, 2005; Ped Derm 17:91–96, 2000; AD 136:875–880, 2000; Ped Derm 16:95– 102, 1999; J Pediatr 123:564–572, 1993; Ped Derm 9:49, 1992; Ped Derm 8:314–321, 1991 STAT5b deficiency – dwarfism, facial dysmorphism, high pitched voice BJD 178:335–349, 2018 STAT1 gain of function mutation – most common cause of chronic mucocutaneous candidiasis; demodicidosis with facial papulopustular eruptions, blepharitis, chalazion, dermatitis of the neck, nail dystrophy, congenital candidiasis Ped Derm 37:159– 161, 2020 Still’s disease – adult onset Still’s disease J Eur Acad Dermatol Venereol 19:360–363, 2005 Toilet seat dermatitis Tuftsin deficiency J. Pediatr 87:1121, 1975 Wiskott-Aldrich syndrome – dermatitis of scalp, face, flexures, napkin area with purpura; alopecia and dermatitis Ped Derm 28:494–501, 2011; Ped Derm 16:95–102, 1999

250 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

CONGENITAL DISORDERS Irritant contact dermatitis of newborn – alcohol burn, perianal, Am J Dis Child 82:429–432, 1951; napkin dermatitis Urachal sinus – presenting as periumbilical psoriasiform dermatitis JAAD 72:1066–1073, 2015; BJD 157:419–420, 2007

135:818–820, 1999; hydroxyurea-associated squamous dysplasia – photodistributed red scaly patches JAAD 51:293–300, 2004 Hypoglycemic agents Indinavir – retinoid-like dermatitis JAAD 63:549–561, 2010 Indomethacin Infliximab – nummular dermatitic drug eruption BJD 151:1272– 1273, 2004

DRUG-INDUCED

INH and ethambutol – generalized dermatitis Cutis 92:121–124, 2013

Acral dysesthesia syndrome – hand dermatitis Aminophylline

Interferon alpha Semin Oncol 14:1–12, 1987; interferon-alpha and ribavirin – nummular dermatitis AD 140:215–217, 2004; peginterferon alpha 2b and ribavirin associated with generalized nummular dermatitis AD 141:102–103, 2005

Ampicillin – baboon syndrome – diffuse erythema of buttocks, inner thighs, axillae Contact Dermatitis 10:97–100, 1984

Ipilimumab – dermatitis, pruritus, enterocolitis, uveitis, iridocyclitis JAAD 71:217–227, 2014

Anti-PD-1 therapy (nivolumab/pembrolizumab – lichenoid eruptions, vitiligo, dermatitis JAAD 74:455–461, 2016

IVIG – widespread dermatitis; dyshidrosiform hand dermatitis JAMA Derm 150:1120–1122, 2014

BCG – instillation for bladder cancer; absorption reaction Cutis 91:145–146,151, 2013

Lichenoid drug eruption – dermatitic appearance JAAD 45:616–619, 2001; – amiphenazole, captopril, gold AD 109:372–376, 1974; isoniazid, levamisole J R Soc Med 73:208–211, 1980; levopromazine, methyldopa, metropromazine, propranolol, exprenolol, labetalol (beta-blockers), chlorpropamide, enalapril, pyrimethamine Clin Exp Dermatol 5:253–256, 1980; antimalarials, penicillamine, thiazide diuretics, streptomycin, hydroxyurea, tiopronin, naproxen, carbamazepine, ethambutol, simvastatin, PAS, pravastatin JAAD 29:249–255, 1993; Cutis 61:98–100, 1998 includes photo-LP (demeclocycline AD 109:97–98, 1974) oral LP, and contact LP; quinacrine – lichenoid dermatitis JAAD 4:239–248, 1981; quinine – lichenoid photodermatitis Clin Exp Dermatol 19:246–248, 1994

Allopurinol

Beta blockers Bismuth JAAD 37:489–490, 1997 Bleomycin Hautarzt 31:616–618, 1980 Butylated hydroxyanisole Calcium channel blockers – chronic dermatitis in the elderly JAMA Derm 149:814–818, 2014 Checkpoint inhibitors – dermatitis JAAD 80:990–997, 2019 Chloramphenicol Cetuximab (epidermal growth factor receptor inhibitor) – painful fissures of fingertips JAAD 55:429–437, 2006

Lovastatin – nummular dermatitis Cutis 62:197–198, 1998

Cimetidine – seborrheic dermatitis-like eruption Clin Dermatol 11:243–251, 1993

Mercurials

Clonidine Demeclocycline – photo-induced lichen planus AD 109:97–98, 1974 Dimethylsulfoxide Disulfiram DRESS syndrome – personal observation Erlotinib (epidermal growth factor receptor inhibitor) – painful fissures of fingertips JAAD 55:429–437, 2006 Everolimus – mTOR inhibitor; broad red patches of face, scalp, upper trunk; also widespread dermatitis, acneiform eruptions The Dermatologist July 2015; pp.47–48 Fixed drug eruption Gold AD 109:372–376, 1974 Hand-foot syndrome secondary to chemotherapy – hand dermatitis with fissuring AD 147:1418–1423, 2011  Capecitabine  Cytarabine  Doxorubicin  5-flurouracil  Taxanes Heparin JAAD 21:1130, 1989; baboon syndrome – diffuse erythema of buttocks, inner thighs, axillae mimicking contact dermatitis Contact Dermatitis 10:97–100, 1984 Hydantoin Hydromorphone, subcutaneous Hydroxyquinone Hydroxyurea – lichenoid dermatitis JAAD 36:178–182, 1997; dermatomyositis-­like scaling eruption of face, hands and feet AD

Lupron – eczematous dermatitis Methyldopa – seborrheic dermatitis-like eruption Clin Dermatol 11:243–251, 1993 Mevastatin – nummular dermatitis Cutis 62:197–198, 1998 Mitomycin (intravesical administration) – exfoliative dermatitis of palms and soles Contact Dermatitis 42:74–76, 2000; dermatitis of face, palms, soles Contact Dermatitis 24:201–209, 1991; BJD 122:217–224, 1990 Nystatin Anti-PD-1 therapy (nivolumab/pembrolizumab – lichenoid eruptions, vitiligo, dermatitis, red papules with scale, red papules and nodules, inflammation surrounding seborrheic keratosis, dyshidrosiform palmar lesions, penile erosions JAMA Derm 152:1128–1136, 2016; JAAD 74:455–461, 2016 Pellagrous dermatitis – phenytoin, INH, 5-fluorouracil, chloramphenicol, pyrazinamide, azathioprine, ethionamide, phenobarbital, 6-­mercaptopurine Semin Dermatol 10:282–292, 1991 Pemetrexed (Alimta) – anti-folate agent; asteatotic dermatitis BJD 166:1359–1360, 2012 Penicillamine – seborrheic dermatitis-like eruption Clin Dermatol 11:243–251, 1993 Penicillin Contact Dermatitis 4:309, 1978 Phenothiazines Pravastatin – nummular dermatitis Contact Derm 30(4):238, 1994; Cutis 62:197–198, 1998 Proton pump inhibitors – airborne contact dermatitis; red face and neck Dermatitis 26:287–290, 2015; lansoprazole and esomeprazole – sticky palms JAMA Derm 152:722–723, 2016 Pyrazolone

Dermatitis (Spongiotic Dermatitis), Differential Diagnosis Quinacrine – lichenoid dermatitis JAAD 4:239–248, 1981

EXOGENOUS AGENTS

Quinine – lichenoid photodermatitis Clin Exp Dermatol 19:246–248, 1994

Benzocaine – erosive papulonodular vulvar dermatitis JAAD 55:S74–80, 2006

Phenothiazines Ranitidine Reactivation of allergic contact dermatitis with systemic agents (systematized contact dermatitis)  Acetohexamide – benzocaine/glyceryl p-aminobenzoic acid sunscreens   Acetylsalicylic acid Semin Dermatol 8:144–148, 1989   Aminophylline suppositories – aminophylline and ethylenediamine  Amlexanox Contact Dermatitis 27:279–280, 1992   Chloral hydrate – chlorobutanol  Chlorothiazide – benzocaine/glyceryl p-aminobenzoic acid sunscreens  Chlorpropamide – benzocaine/glyceryl p-aminobenzoic acid sunscreens  Codeine Contact Dermatitis 32:120, 1995  Disulfiram (Antabuse) – thiuram; baboon syndrome – diffuse erythema of buttocks, inner thighs, axillae Contact Dermatitis 10:97–100, 1984  Enoxolone Contact Dermatitis 30:124, 1994  Ephedrine Contact Dermatitis 29:215–216, 1993  Erythromycin Contact Dermatitis 30:311, 1994   Ethylenediamine – aminophylline and ethylenediamine  Iodochlorhydroxyquinolone – halogenated hydroxyquinolone cream  Iodides, iodinated organic compounds, radiographic contrast media – iodine  Isoniazid Contact Dermatitis 28:110–111, 1993   Nitroglycerin tablets – nitroglycerin ointment  p-amino salicylic acid – benzocaine/glyceryl p-aminobenzoic acid sunscreens   Paraben-containing systemic medications AD 110:640, 1974  Phenobarbital   Piperazine – aminophylline and ethylenediamine  Pseudoephedrine hydrochloride and norephedrine hydrochloride Contact Dermatitis 24:86–88, 1991  Organic and inorganic mercury compounds – ammoniated mercury   Tincture of benzoin inhalation – Balsam of Peru   Procaine – benzocaine/glyceryl p-aminobenzoic acid sunscreens  Streptomycin, kanamycin, paromomycin, gentamicin – neomycin sulfate  Tolbutamide – benzocaine/glyceryl p-aminobenzoic acid sunscreens   Vitamin B1   Vitamin C Retinoid dermatitis – sticky palms JAMA Derm 152:722–723, 2016 SDRIFE – symmetric drug-related intertriginous and flexural exanthema (baboon syndrome) Am J Clin Dermatol 12:171–180, 2011

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Coffee – hand dermatitis of coffee drinkers Cutis 40:421–422, 1987 Contact  Irritant contact dermatitis JAAD 55:891–896, 2006; The Clinical Management of Itching; Parthenon; p. 79, 2000; hand dermatitis Cutis 82(suppl 4)9–15, 2008; Ranunculus kostschyi Dermatitis 25:140–146, 2014; tartar control toothpaste personal observation  Photocontact   Plant irritant dermatitis SKINmed 12:253–255, 2014   Agave americana   Narcissus pseudo-narcissus   Dieffenbachia picta   Philodendron spp.   Ananas cosmosus   Armoracia rusticana   Brassica oleracea   Brassica nigra   Raphanus sativus   Sinapis alba   Euphorbia spp.   Codiaeum variegatum   Hippomane mancinella   Ricinus communis   Hyacinthus orientalis   Rheum rhaponticum   Anemone pavonina   Ranunculus acer   Aquilegia vulgaris   Caltha palustris   Capsicum frutescens   Capsicum annuum   Seaweed dermatitis   Windborne pollen dermatitis Hydroxytoluene Lymphomatoid contact dermatitis JAAD 38:877–905, 1998 Marlex graft, with secondary infection Mercury – baboon syndrome – diffuse erythema of buttocks, inner thighs, axillae Contact Dermatitis 10:97–100, 1984 Nickel – baboon syndrome – diffuse erythema of buttocks, inner thighs, axillae Contact Dermatitis 10:97–100, 1984 Plant irritant contact dermatitis – buttercup, spurge, manzanillo tree, milfoil, mayweed, tulip fingers, daffodil itch (raphides – calcium oxalate) Contact Dermatitis 20:63–78, 2009; barley – interdigital dermatitis Slime – irritant contact dermatitis Ped Derm 36:335–337, 2019; Ped Derm 36:139–141, 2019 Sponge dermatitis Tea tree oil Contact Dermatitis 27:279–280, 1992

Simvastatin – nummular dermatitis Cutis 62:197–198, 1998 Sorafenib – hyperkeratotic dermatitis of palmar creases – personal observation

INFECTIONS AND INFESTATIONS

Sulfonamides

Acanthamebiasis – adult facial dermatitis; personal observation

Sunitinib – erythematous scaling scrotal dermatitis NEJM 359:975– 976, 2008; hand dermatitis – personal observation

African histoplasmosis (Histoplasma capsulatum var. duboisii) -exclusively in Central and West Africa and Madagascar Clin Inf Dis 48:441, 493–494, 2009

Vemurafenib and radiation recall dermatitis JAMA Derm 149:855– 857, 2013 Vitamin K injection

Alternariosis – dermatitic rash BJD 145:484–486, 2001; BJD 143:910–912, 2000

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Ancylostomiasis – papular or papulovesicular rash; feet; generalized urticaria; late changes resemble kwashiorkor Dermatol Clin 7:275–290, 1989 Anemones (Cnidarians) – contact urticaria JAAD 61:733–750, 2009 AIDS – pruritic papular eruption of AIDS; firm discrete red, hyperpigmented urticarial papules JAMA 292:2614–2621, 2004; atopic dermatitis-­like eruption Brucellosis – contact brucellosis with brucella dermatitis Cutis 63:25–27, 1999; AD 117:40–42, 1981 Candidiasis, including chronic mucocutaneous candidiasis; neonatal mucocutaneous candidiasis; invasive systemic candidiasis in premature neonate (C. albicans) – crusted and erosive dermatitis, red plaques Ped Derm 21:260–261, 2004

Impetigo Infectious eczematoid dermatitis Insect bites Jellyfish (Cnidarians) – contact urticaria JAAD 61:733–750, 2009 Leishmaniasis – facial dermatitis resembling syphilis, atopic dermatitis JAAD 60:897–925, 2009; JAAD 51:S125–128, 2004; Clinics in Derm 14:425–431, 1996; hand dermatitis Clin Dermatol 38:140–151, 2020 Leprosy – non-pruritic dermatitis as presenting manifestation Indian J Lepr 62:202–207, 1990 Lyme disease – personal observation Majocchi’s granuloma

Caterpillar dermatitis (lepidopterism) – Io moth, buch moth, puss moth

Molluscum contagiosum – dermatitis surrounding the mollusca (molluscum dermatitis) AD 148:1257–1264, 2012

Ciguatera dermatitis – ciguatoxin produced by dinoflagellates (Gambierdiscus toxicus) – Caribbean and Gulf of Mexico JAAD 61:733–750, 2009

Necator americanus – ground itch

Clam digger’s itch (ghost anemone dermatitis) (Haloclava producta) – vesiculopapular eruption of hands, wrists, knees, inner thighs, ankles JAAD 47:722–726, 2002 Coral dermatitis (Cnidarians) – contact urticaria JAAD 61:733–750, 2009 Cryptococcosis AD 132:545–548, 1996 Cutaneous larva migrans – Ancylostoma brasiliensis, A. caninum, Bunostomum phlebotomum, Uncinaria stenocephala, Gnathostoma spinigerum, Dirofilaria species, Strongyloides procyonis, S. stercoralis Ped Derm 15:367–369, 1998; South Med J 89:609–611, 1996

Onchocerciasis – Onchecerca volvulus; transmitted by Simuliidae (humpbacked black fly) localized acute dermatitis or chronic generalized dermatitis; papules, crusted papules, lichenified plaques; often with hyperpigmented nodules; atrophy and depigmentation JAAD 73:929–944, 2015; BJD 171:1078–1083, 2014; AD 140:1161–1166, 2004; JAAD 45:435–437, 2001; Cutis 65:293–297, 2000; BJD 121:187–198, 1989 Phaeohyphomycosis AD 137:815–820, 2001 Pinworm infection (Enterobius vermicularis) – palmar dermatitis AD 148:1073–1078, 2012 Protothecosis JAAD 32:758–764, 1995 Scabies – widespread dermatitis Ped Derm 27:525–526, 2010;

Cyanobacteria (blue-green algae) – algae microfilaments retained on bathing trunks; contact dermatitis JAAD 61:733–750, 2009

localized nummular plaques; crusted (Norwegian scabies) – may mimic hyperkeratotic dermatitis, psoriasis, contact dermatitis Dermatology 197:306–308, 1998; AD 124:121–126, 1988

Demodicidosis – papular eruption in HIV patients of head and neck, trunk, and arms JAAD 20:306–307, 1989; JAAD 20:197–201, 1989

Seabather’s dermatitis – larvae of Scyphozoa JAAD 61:733–750, 2009

Dermatophilus congolensis – due to contact with infected animals; exudative scaly dermatitis BJD 145:170–171, 2001

Sponge dermatitis (Phylum Poriphera) – spicules JAAD 61:733– 750, 2009; freshwater sponges – generalized papular eruption JAAD 61:733–750, 2009

Dermatophytid Ped Derm 32:635–640, 2015; Acta DV 74:403–404, 1994; Semin Dermatol 2:60, 1983

Staphylococcal scalded skin syndrome

Erythrasma – disciform erythrasma; intertriginous and perigenital; Corynebacterium minutissimum; red to brown irregularly shaped and sharply marginated scaly and slightly creased patches of groin, axillae, intergluteal, submammary flexures, toe clefts are most frequent location; coral-red fluorescence with Wood’s light examination due to coproporphyrin; acanthosis nigricans and normal follicular openings of face and trunk may show coral pink fluorescence Rev Infect Dis 4:1220–1235, 1982

Streptocerciasis – Mansonella streptocerca – similar rash to onchocerciasis; acute or lichenified papules with widespread lichenification and hypopigmented macules; pruritus, lymphadenopathy JAAD 73:929–944 2015 Syphilis – congenital, secondary Sem Diagn Pathol 34:220–225, 2017; scrotal dermatitis in secondary syphilis JAAD 57:1099–1101, 2007

Histoplasmosis JAAD 25:418, 1991; Cutis 43:535–538, 1989

Tinea corporis – Trichophyton rubrum, T. megninii, E.floccosum; dermatitic dermatophytosis; Trichophyton verrucosum – extensive annular lesions of trunk and neck AD 94:35–37, 1966; tinea corporis, pedis – bullous or scaly Rook p.1300–1301, 1998, Sixth Edition; capitis, corporis (also with overlying lichen simplex chronicus), manuum, pedis, cruris; tinea incognito Mycoses 49:383–387, 2006; tinea incognito – hand dermatitis – personal observation

HIV – dermatitis of HIV disease including HIV disease in children JAAD 20:1130, 1989; nummular dermatitis of AIDS; HIV-1 dermatitis – lichenoid photodermatitis JAAD 28:167–173, 1993

Tinea imbricata- Trichophyton concentricum – extensive involvement with pruritus and lichenification Clin Exp Dermatol 13:232– 233, 1988; Trans R Soc Trop Med Hyg 78:246–251, 1984

HTLV-1 infection – infective dermatitis of scalp, upper lip, eyelid margins, perinasal skin, retro-auricular areas, axillae, groin BJD 150:958–965, 2004; generalized papular dermatitis BJD 150:958– 965, 2004; JAAD 49:979–1000, 2003; AD 134:439–444, 1998; Lancet 336:1345–1347, 1990; BJD 79:229–236, 1967; BJD 78:93–100, 1966

Tinea versicolor – personal observation

Fire coral (Millepora spp) – scuba divers; dermatitis, bullae, hemorrhagic bullae, necrosis, ulceration, urticaria; late lichenoid and granulomatous reactions JAAD 61:733–750, 2009 Gianotti-Crosti syndrome Indian J Dermatol Venereol Leprol 74:523–526, 2008

Tungiasis (Tunga penetrans, Tunga trimamillata) – papules on tips of toes, paronychia, and plantar dermatitis JAAD 82:551–569, 2020 Toxocariasis – generalized dermatitis JAAD 75:19–30, 2016; JAAD 59:1031–1042, 2008

Dermatitis (Spongiotic Dermatitis), Differential Diagnosis

INFILTRATIVE DISEASES Amyloidosis – primary cutaneous amyloidosis – lichenified dermatitis; dome-shaped skin colored 3–4mm papules; autosomal dominant; mutation in oncostatin M receptor BJD 161:944–947, 2009 Langerhans cell histiocytosis – cutaneous findings include crops of red-brown or red-yellow papules, vesicopustules, erosions, scaling, and seborrheic dermatitis-like papules, petechiae, purpura, solitary nodules, bronze pigmentation, lipid infiltration of the eyes, white plaques of the oral mucosa, onycholysis, and onychodystrophy Curr Prob Derm VI Jan/Feb 1994; Clin Exp Derm 11:183–187, 1986; JAAD 13:481–496, 1985; purpuric papules in the neonate; masquerading as lichen aureus Ped Derm 8:213–216, 1991; Letterer-Siwe disease JAAD 18:646– 654, 1988; purpuric vesicles JAAD 37:314–317, 1997

INFLAMMATORY DISORDERS Hidradenitis suppurativa Sarcoid – dermatitis-like lesions in children Clin Exp Dermatol 15:60–62, 1990; JAAD 5:566–570, 1981 Stevens-Johnson syndrome – adult facial dermatitis; personal observation Toxic epidermal necrolysis – adult facial dermatitis; personal observation Whipple’s disease – dermatitis; macular and reticulated erythema; Addisonian hyperpigmentation; Tropheryma whipplei JAAD 60:277–288, 2009

METABOLIC Acral necrolytic erythema – hyperpigmented hyperkeratotic palmar dermatitis and dorsal fingers JAAD 60:584–487, 2009; Int J Dermatol 35:252–256, 1996; zinc deficiency JAAD 55:S108–110, 2006 Acrodermatitis enteropathica – hands, feet, anogenital region, periorificial, palmar flexures; periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche; mutation in SLC39A4 encodes ZIP4 zinc transporter BJD 161:184–186, 2009; JAAD 56:116–124, 2008;Ped Derm 19:426–431, 2002; Textbook of Neonatal Dermatology, p. 150, 2001; Curr Prob in Derm 10:41–92, 1998; chronic zinc deficiency – thickened brown dermatitis over elbows, knees, knuckles, malleoli; lichenification with scaling; scrotal dermatitis; zinc deficiency – dermatitis of buttocks Cutis 101:450– 453, 2018 A histidinemia Curr Prob in Derm 10:41–92, 1998 Asymmetric periflexural exanthem of childhood – unilateral laterothoracic exanthem; dermatitic Ped Derm 19:461–462, 2002; Ped Derm 12:112–115, 1995 Atopic eruption of pregnancy J Drugs Dermatol 14:512–513, 2015 Biotinidase deficiency – combination of eczematous dermatitis and neurologic symptoms Carcinoid syndrome – pellagrous dermatitis (skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, salivation, lacrimation, abdominal cramping, wheezing, diarrhea BJD 152:71–75, 2005; AD 77:86–90, 1958; Am Heart J 47:795–817, 1954 Celiac disease – atopic dermatitis-like eruption Rook p.700, 1998, Sixth Edition; Lancet i:115–117, 1976

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Cystic fibrosis – generalized dermatitis in infancy; failure to thrive with diffuse rash, hypoproteinemia, anemia JAAD 58:s1–4, 2008; differential diagnosis includes Wiskott-Aldrich syndrome, Netherton’s syndrome, subacute combined immunodeficiency, acrodermatitis enteropathica, kwashiorkor, biotinidase deficiency; heterozygote Lancet i:990–991, 1976; acrodermatitis enteropathicalike eruption with hypoproteinemia, anemia, and edema AD 146:171–174, 2010; JAAD 58:S5–8, 2008 Glucagonoma syndrome (necrolytic migratory erythema) – scaling papules and plaques Skin and Allergy News Vol 32, July 2001, pp. 1,59; necrolytic migratory erythema also seen in gluten-sensitive enteropathy, celiac disease, cirrhosis, hepatocellular carcinoma, bronchial carcinoma, pancreatitis, hepatitis, and inflammatory bowel disease Hartnup’s disease Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; presenting in adulthood Clin Exp Dermatol 19:407–408, 1994 Hereditary spherocytosis – dermatitis of the legs Ped Derm 20:427–428, 2003 Homocystinuria Kwashiorkor – enamel paint change; may resemble atopic dermatitis on the face; red brown scaly plaques JAAD 52:S69–72, 2005; JAAD 21:1–30, 1989; in elderly, cracked skin on lower abdomen and pretibial areas (geriatric nutritional eczema) Leiner’s disease Pediatrics 49:225–232, 1972 Liver disease, chronic (cirrhosis) – zinc deficiency; generalized dermatitis of erythema craquele (crackled and reticulated dermatitis) with perianal and perigenital erosions and crusts; cheilitis, hair loss Ann DV 114:39–53, 1987 Malabsorption Br Med J ii:937–943, 1962; Q J Med 22:59–79, 1953; scrotal dermatitis Malnutrition – personal observation Multiple Carboxylase Deficiency Nephrotic syndrome – atopic dermatitis-like eruption Lancet i:388–390, 1977 Pellagra – associated with celiac disease Yale J Biol Med 72:1518, 1999; scrotal dermatitis Phenylketonuria – resembles atopic dermatitis JAAD 49:S190–192, 2003; Curr Prob in Derm 10:41–92, 1998 Phosphoglucomutase 3 deficiency (PGM3) – atopic dermatitis, hypergammaglobulinemia, lymphopenia, neutropenia, developmental delay Dermatol Clinics 35:11–19, 2017; J Allergy Clin Immunol 133:1400–1409, 2014 Porphyria – erythropoietic protoporphyria – may be confused with atopic dermatitis BJD 155:574–581, 2006; Eur J Pediatr 159:719– 725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751– 766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976 Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, xerosis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; BJD 144:635–636, 2001; Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987 Prurigo of Besnier

254 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Prurigo of pregnancy – red papules Semin Derm 8:23–25, 1989

PARANEOPLASTIC

Pseudoglucagonoma syndrome due to malnutrition AD 141:914– 916, 2005

Adult-onset recalcitrant eczema – marker of non-cutaneous lymphoma or leukemia JAAD 43:207–210, 2000

Pruritic urticarial papules and plaques of pregnancy (PUPPP) – personal observation Vitamin B2 (riboflavin) deficiency – scrotal dermatitis; crusting of scrotum JAAD 68:211–243, 2013

Bazex syndrome – dermatitis of hands, feet, nose, ears JAAD 40:822–825, 1999

Vitamin B6 (pyridoxine) deficiency

Generalized erythema craquele as a paraneoplastic phenomenon; lymphoma BJD 97:323–326, 1977; angioimmunoblastic lymphadenopathy AD 115:370, 1979; gastric carcinoma BJD 109:277–278, 1983; breast cancer BJD 110:246, 1984

NEOPLASTIC

Necrolytic migratory erythema – nummular dermatitis-like lesions Cutis 81:25,30–32, 2008

Basal cell carcinoma

Paraneoplastic nummular dermatitis – personal observation

Bowen’s disease Cervicothoracic syrinx and thoracic spinal cord tumor – dermatomal lichen simplex chronicus Neurosurgery 30(3):418–421, 1992 Clear cell acanthoma of nipple – psoriasiform plaque JAAD 80:749–755, 2019 Dermatofibroma – halo dermatitis (Meyerson’s phenomenon) BJD 159:496, 2008 Disseminated superficial actinic porokeratosis Epidermal nevus (dermatitic epidermal nevus) Extramammary Paget’s disease of scrotum JAAD 57:S43–45, 2007 Leukemia – HTLV-1 leukemia/lymphoma (acute T-cell leukemia) Leukemia cutis – mimicking stasis dermatitis Cutis 35:47–48, 1985

PHOTODERMATOSES Actinic prurigo (polymorphic light eruption of American Indians) – dermatitis with lichenification The Dermatologist May, 2015,pp47– 48, 50, 2015; JAAD 44:952–956, 2001; Australas J Dermatol 42:192–195, 2001; Photodermatol Photoimmunol Photomed 15:183–187, 1999; Int J Dermatol 34:380–384, 1995; JAAD 26:683–692, 1992; JAAD 5:183–190, 1981; Clin Exp Dermatol 2:365–372, 1977; familial, in North American Indians Int J Dermatol 10:107–114, 1971; occurrence in non-Indians JAAD 34:612–617, 1996; in Caucasians BJD 144:194–196, 2001;; Southeast Asian Photodermatol Photoimmunol Photomed 9:225–228, 1992

Leukemid – personal observation

Actinic reticuloid Sem Derm 161, Sept 1982; JAAD 38:877–905, 1998; AD 115:1078–1083, 1979

Lymphoma – early sign of Sezary syndrome JAAD 77:719–727, 2017; cutaneous B-cell lymphoma AD 123:136–137, 1987; cutaneous T-cell lymphoma; small to medium-sized pleomorphic T-cell lymphoma JAAD 46:531–535, 2002; Woringer-Kolopp disease – red scaly foot dermatitis Cutis 90:307–309, 2012; syringolymphoid hyperplasia with alopecia (CTCL) – nummular dermatitis-like lesions BJD 110:95–101, 1984; HTLV-1 leukemia/ lymphoma – infective dermatitis; adult facial dermatitis JAAD 81:23–41, 2019

Chronic actinic dermatitis – acute, subacute, or chronic dermatitis with lichenification, papules, plaques, erythroderma, stubby scalp and eyebrow hair JAMA Derm 153:427–435, 2017; BJD 152:784– 786, 2005; AD 136:1215–1220, 2000; AD 130:1284–1289, 1994; JAAD 28:240–249, 1993; AD 126:317–323, 1990; sensitization by sesquiterpene lactone mix BJD 132:543–547, 1995; associated with musk ambrette Cutis 54:167–170, 1994; JAAD 3:384–393, 1980

Lymphomatoid papulosis – personal observation Malignant histiocytosis mimicking kwashiorkor Ped Derm 19:5–11, 2002 Melanocytic nevi, congenital – dermatitis within large congenital nevi JAAD 61:766–774, 2009

Juvenile spring eruption Ped Derm 36:533–534, 2019 Photoallergic contact dermatitis Photosensitive eczema Polymorphic light eruption – papulovesicular

Melanoma – “eczema-like melanoma” AD 143:1081–1082, 2007; J Dtsch Dermatol Ges 2:597–600, 2004; Semin Cutan Med Surg 16:122–130, 1997; AD 119:423–425, 1983

PRIMARY CUTANEOUS DISEASES

Meyerson’s nevus – dermatitic halos surrounding melanocytic nevi, atypical nevi, congenital nevus Int J Dermatol 42:895, 2003; seborrheic keratoses Clin Exp Dermatol 27:73, 2002;, stucco keratoses, keloids, benign lentigo, insect bite, basal cell carcinoma, squamous cell carcinoma, dermatofibroma, pityriasis rosea AD 139:1209–1214, 2003; Australas J Dermatol 18:81–83, 1997; Int J Dermatol 24:226–229, 1985; AD 103:510–512, 1971; molluscum contagiosum BJD 131:452, 1994; port wine stain JAAD 35:811– 813, 1996; due to interferon-alpha and ribavirin BJD 152:193–194, 2005; JAAD 40:105–106, 1999; BJD 118:125–129, 1988; Int J Dermatol 24:226–229, 1985; Am J Dermatopathol 6:257–259, 1984; atypical nevus JAAD 34:357–361, 1996; nevus sebaceus Ped Derm 28:176–179, 2011

Acanthosis nigricans – resembling dermatitis Ped Derm 19:12–14, 2002

Nevi – widespread dermatitis with underlying eruptive atypical nevi JAMA Derm 152:1021–1024, 2016

Blaschkitis – in the adult/adult onset lichen striatus Eur J Dermatol 29:281–286, 2019; acquired relapsing self-healing Blaschko dermatitis J Dermatol 23:639–642, 1996

Parapsoriasis en plaque

Absorption reaction – personal observation

Alopecia mucinosa Clin Exp Derm 14:382–384, 1989 Amicrobial pustulosis – exudative erythema, erosions, pustules, diffuse alopecia with dermatitis; associated with systemic autoimmune disorders; scalp, axillae, ears, thighs JAAD 57:523–526, 2007; BJD 154:568–569, 2006; Communication no.11. Journees Dermatologiques de Paris, March 1991. Annular lichenoid dermatitis of youth – pityriasis rosea-like dermatitis JAMA Derm 154:357–358, 2018; Asteatotic dermatitis, including erythema craquele Atopic dermatitis

Dermatitis (Spongiotic Dermatitis), Differential Diagnosis Brachioradial pruritus – lichen simplex chronicus of the arm JAAD 29:783–784, 1983

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Interstitial granulomatous dermatitis

Darier's disease – mimicking dermatitis J Laryngol Otol 106:725– 726, 1992

Juvenile plantar dermatosis Clin Exp Dermatol 11:529–534, 1986; Semin Dermatol 1:67–75, 1982; Clin Exp Dermatol 1:253–260, 1976

Dermatitis herpetiformis-like spongiotic dermatitis – of elbows, knees, buttocks in middle aged women; personal observation

Kawasaki’s-like syndrome of HIV disease – adult facial dermatitis; personal observation

Diaper dermatitis – with rapid dissemination – expanding nummular dermatitis of trunk, and red scaly plaques of neck and axillae (“psoriasiform id”) BJD 78:289–296, 1966

Keratolysis exfoliativa

Digitate dermatosis (small plaque parapsoriasis) (persistent superficial dermatitis) Dyshidrotic dermatitis; dyshidrosis with secondary infection and lymphedema of hand BJD 161:177–180, 2009 Eczematoid-like pigmented purpuric eruption of Doukas and Kapetanakis Ped Derm 32:291–292, 2015 Eosinophilic pustular dermatosis of the palms and soles – personal observation Eosinophilic pustular folliculitis of AIDS Epidermolysis bullosa pruriginosa – mild acral blistering at birth or early childhood; violaceous papular and nodular lesions (prurigo nodularis-­like) in linear array on shins, forearms, trunk; dermatitis with lichenified hypertrophic and verrucous plaques in adults, albopapuloid lesions of the trunk, milia, hyperkeratosis of nails JAMA Derm 149:727–731, 2013; BJD 152:1332–1334, 2005; AD 140:794–796, 2004; BJD 130:617–625, 1994 Epidermolysis bullosa simplex – personal observation Erythema annulare centrifugum Erythrokeratoderma variabilis Curr Prob in Derm 10:41–92, 1998 Exfoliation of the newborn Exfoliative dermatitis/exfoliative erythroderma Int J Dermatol 56:400–404, 2017 Exudative discoid and lichenoid dermatosis of Sulzberger and Garbe (oid-oid disease) BJD 100:13–20, 1979; AD 36:247–272, 1937 Fissured hand dermatitis – loss of function mutation in filaggrin BJD 166:46–53, 2012 Frictional dermatitis of children – pinhead-sized white papules or warty lesions of backs of hands, elbows, and knees

Keratosis lichenoides chronica (Nekam’s disease) – reticulated flat-­topped keratotic papules, linear arrays, atrophy, comedo-like lesions, prominent telangiectasia; conjunctival injection, seborrheic dermatitis-­like eruption; acral dermatitis over toes; punctate keratotic papules of palmar creases Ped Derm 26:615–616, 2009; AD 145:867–69, 2009; AD 144:405–410, 2008;JAAD 49:511–513, 2003; Dermatology 201:261–264, 2000; JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; AD 131:609–614, 1995; AD 105:739–743, 1972; Arch Dermatol Syph (Berlin) 31:1–32, 1895; in children JAAD 56:S1–5, 2007 Kimura’s disease (eosinophilic pustular folliculitis) BJD 157:420– 421, 2007; Pediatr Nephrol 18:1069–1072, 2003; Cutis 70: 57–61, 2002; Dermatology 18:145–148, 1992; HIV-associated Lichen nitidus – palmar lesions resemble chronic fissured dermatitis, palmar hyperkeratosis Clin Exp Dermatol 18:381–383, 1993; minute papules AD 104:538–540, 1971; dyshidrosis-like BJD 82:423–424, 1976 Lichen planus – mimicking hyperkeratotic hand dermatitis Rook p.656, 1998, Sixth Edition; generalized dermatitis Lichen simplex chronicus (neurodermatitis) – personal observation Lichen striatus Int J Dermatol 25:584–585, 1986 Lip lickers dermatitis – perioral dermatitis and hyperpigmentation Necrolytic acral erythema Int J Derm 35:252–256, 1996 Nipple dermatitis Nummular dermatitis Ped Derm 35:611–615, 2018 Pachydermatous eosinophilic dermatitis (hypereosinophilic dermatitis) – resembles severe atopic dermatitis with hypertrophic genital lesions BJD 134:469–474, 1996; Dermatologica 162:444– 450, 1981 Palmar dermatitis AD 131:325–329, 1995 Papular prurigo (chronic prurigo of adults)

Granuloma annulare – personal observation

Parapsoriasis

Granular parakeratosis Ped Derm 20:215–220, 2003

Perioral dermatitis

Grover’s disease (transient acantholytic dermatosis) JAAD 25:653–666, 1996; AD 101:426–434, 1970

Peristomal irritant contact dermatitis – annular scaling dermatitis BJD 166:103–109, 2012

Hailey-Hailey disease Australas J Dermatol 37:196–198, 1996; BJD 126:275–282, 1992; Arch Dermatol Syphilol 39:679–685, 1939

Pityriasis alba Int J Dermatol 32:870–873, 1993

Halo dermatitis Ped Derm 9:275, 1992

Pityriasis rubra pilaris – seborrheic dermatitis facial and scalp rash in infants BJD 157:202–204, 2007; dermatitic patches in atypical adult PRP

Hand dermatitis – numerous etiologies including allergic contact dermatitis (quaternium-15, formaldehyde, nickel sulfate, fragrance, thiuram, balsam of Peru, carba mix, neomycin sulfate, bacitracin, methyldibromoglutaronitrile/phenoxyethanol, rubber, tulip fingers, etc.), irritant contact dermatitis, dyshidrosis, ingested allergens (nickel, chromium), dermatophytid, atopic, water exposure (“housewives dermatitis”) JAAD 77:123–129, 2017; NEJM 367:1829–1837, 2012; JAAD 57:301–314, 2007 Hyperkeratotic dermatitis of the palms and soles JAAD 77:123–129, 2017; BJD 109:205–208, 1983; BJD 107:195–202, 1982 Ichthyosis Id reaction to inflammatory dermatitis – personal observation Infectious eczematoid dermatitis – personal observation

Pityriasis rosea – adult facial dermatitis; personal observation

Progressive symmetric erythrokeratoderma – palmar dermatitis; adult facial dermatitis; personal observation Prurigo pigmentosa Cutis 63:99–102, 1999; BJD 120:705–708, 1989; AD 125:1551–1554, 1989 Psoriasis – hand dermatitis JAAD 77:123–129, 2017; napkin psoriasis Psoriasiform spongiotic dermatitis Sem Diagn Pathol 34:220–225, 2017 Vegetative pustular neutrophilic dermatitis – personal observation Ring dermatitis – due to soap and/or water trapped under a ring; due to radioactive gold JAMA 205:595–596, 1968

256 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Seborrheic dermatitis – scalp, nasolabial folds, umbilicus, groin, axillae; yellow-brown adherent scale of scalp; scales smaller, whiter, and drier of face, axillae Subcorneal pustular dermatitis Sulzberger-Garb exudative discoid and lichenoid chronic dermatosis (“oid-oid” disease); nummular dermatitis with scrotal areolar and back involvement; “executive eczema” Syringolymphoid hyperplasia JAAD 49:1177–1180, 2003 Transient acantholytic dermatosis (Grover’s disease) JAAD 35:653–666, 1996 Unilateral laterothoracic exanthem of childhood – scarlatiniform or dermatitic JAAD 27:693–696, 1992 Vorner’s palmoplantar keratoderma – neonatal BCIE-like dermatitis

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis Ped Derm 21:205–211, 2004 Hand dermatitis – obsessive compulsive disorder with repeated hand washing JAAD 13:965–967, 1985

SYNDROMES Andogsky syndrome – atopic dermatitis and unilateral cataracts Ped Derm 20:419–420, 2003; Klin Monatsbl Augenheilkd 52:824–831, 1914 Anhidrotic ectodermal dysplasia Ankyloblepharon-ectrodactyly-cleft lip/palate (AEC syndrome) – severe dermatitis; congenital scalp erosions AD 134:1121–1124, 1998; Ped Derm 10:334–340,1993; generalized fissured erosions of trunk BJD 149:395–399, 2003 Apert’s syndrome – autosomal dominant; FGFR-2 mutation; craniosynostosis with midfacial malformation; cone shaped calvarium, proptosis, hypertelorism, short nose with bulbous tip; high arched palate; lips bow-shaped, unable to form a seal; telangiectasias of face and bulbar conjunctiva, often in butterfly distribution; mottled hyperpigmentation, hypopigmentation and poikiloderma; seborrheic dermatitis, atopic dermatitis, and xerosis common Am J Med Genet 44:82–89, 1992; severe pustular acne at puberty Ped Derm 20:443–446, 2003 Ataxia telangiectasia – dermatitis; telangiectasias of bulbar conjunctivae, tip of nose, ears, antecubital and popliteal fossae, dorsal hands and feet; atrophy with mottled hypo- and hyperpigmentation, dermatomal CALMs, photosensitivity, canities, acanthosis nigricans, dermatitis; cutaneous granulomas present as papules or nodules, red plaques with atrophy or ulceration BJD 178:335–349, 2018; JAAD 10:431–438, 1984; Ann Int Med 99:367–379, 1983 Bazex syndrome Bazex-Dupre-Christol syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Ped Derm 25:112–113, 2008; Ped Derm 23:286–290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Cardio-facio-cutaneous syndrome – autosomal dominant, xerosis/ ichthyosis, eczematous dermatitis, alopecia, growth failure,

hyperkeratotic papules, ulerythema ophryogenes (decreased or absent eyebrows), seborrheic dermatitis, CALMs, nevi, hemangiomas, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly scalp hair and sparse eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies with macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of supraorbital ridges, short nose with depressed nasal bridge, high arched palate, low set posteriorly rotated ears with prominent helices, cardiac defects; gain of function sporadic missense mutations in BRAF, KRAS, MEK1, or MEK2, MAP2K1/MAP2K2 BJD 163:881–884, 2010; Ped Derm 27:274–278, 2010; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992 Down’s syndrome – lichenified dermatitis of neck and extremities Dubowitz syndrome – autosomal recessive, microcephaly, sloping forehead, telecanthus, erythema and scaling of face and extremities in infancy, sparse blond scalp and arched eyebrow hair, dysplastic low set ear pinnae, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities; syndactyly, cryptorchidism, hypospadias, developmental delay, transitory short stature, hyperactive behavior, blepharophimosis, ptosis of the eyelids, epicanthal folds, broad nose, palate anomalies, micrognathia, and severe atopic dermatitis Ped Derm 22:480–481, 2005; Am J Med Genet 63:277–289, 1996; Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959–964, 1993; Eur J Pediatr 144:574– 578, 1986; Am J Med Genet 4:345–347, 1979; J Med Genet 2:12–17, 1965 Ectrodactyly-ectodermal dysplasia-clefting syndrome – alopecia of scalp, eyebrows, and eyelashes, xerosis, atopic dermatitis, nail dystrophy, hypodontia with peg shaped teeth, reduced sweat glands and salivary glands, syndactyly, mammary gland and nipple hypoplasia, conductive or sensorineural hearing loss, urogenital anomalies, lacrimal duct abnormalities; TP63 mutations BJD 162:201–207, 2010; scalp dermatitis BJD 132:621–625, 1995 Ectodermal dysplasias Hearing loss with atopic dermatitis (familial) – atopic dermatitis-like eruption Acta Otolaryngol 82:242, 1976 Hereditary acrokeratotic poikiloderma – vesicopustules of hands and feet at 1–3 months of age; widespread atopic dermatitis-like dermatitis; keratotic papules of hands, feet, elbows, and knees AD 103:409–422, 1971 Hurler’s syndrome Hyper IgE syndrome (Job’s syndrome) (Buckley’s syndrome) – papular, pustular, excoriated dermatitis of scalp, buttocks, neck, axillae, groin; furunculosis; growth failure; dermatitis of face, behind ears, scalp, axillae, and groin; recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract J Pediatr 141:572–575, 2002; NEJM 340:692–702, 1999; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983; Lancet 1:1013– 1015, 1966; cyst-forming pneumonia, elevated IgE levels; STAT3 mutations AD 144:1662–1663, 2008; NEJM 357:1608–1619, 2007; JAAD 54:855–865, 2006 Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked recessive; atopic dermatitis; collodion membrane and erythema at birth; ichthyosis, spiny (keratotic) follicular papules (generalized follicular keratoses), non-scarring alopecia totalis, keratotic papules of elbows, knees, fingers, Achilles tendons; extensor surfaces, xerosis; punctate keratitis, photophobia with progressive corneal scarring; nail dystrophy, paronychia, psychomotor delay, short stature; enamel dysplasia, beefy red tongue and gingiva, angular

Dermatitis (Spongiotic Dermatitis), Differential Diagnosis stomatitis (angular cheilitis), lamellar scales, psoriasiform plaques, palmoplantar erythema; mutation of MBTPS2 (intramembrane zinc metalloproteinase needed for cholesterol homeostasis and endoplasmic reticulum stress response) JAAD 64:716–722, 2011; Ped Derm 26:427–431, 2009; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; AD 125:103– 106, 1989; Ped Derm 12:195, 1995; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999; BJD 21:165–189, 1909 Hypereosinophilic syndrome, idiopathic AD 142:121501218, 2006; BJD 144:639, 2001; Blood 83:2759–2779, 1994; atopic dermatitislike eruption Immuno-osseous dysplasia – widespread dermatitis, alopecia, renal disease, short-limbed dwarfism, immunodeficiency with impaired humoral immunity, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation) Ped Derm 23:373–377, 2006; J Pediatr 84:200–203, 1974; J Pediatr 5:675– 684, 1969; spondylo-­epithelial dysplasia and mixed immune defect with widespread dermatitis J Med Genet 28:10–17, 1991; J Pediatr 80:1010–1017, 1980 Incontinentia Pigmenti Infantile systemic hyalinosis – mimicking atopic dermatitis; joint contractures, short stature, thickened skin and hyper pigmentation, pearly papules of face, perianal nodules, gingival hyperplasia, increased susceptibility to infection, osteopenia, protein losing enteropathy; mutation in CMG2 (capillary morphogenesis protein 2) JAAD 58:303–307, 2008; Pediatr Pathol 6:55–79, 1986 IPEX syndrome – X-linked; immune dysregulation, polyendocrinopathy (diabetes mellitus, thyroiditis), autoimmune enteropathy; mutation of FOXP3 gene encodes DNA-binding protein that suppresses transcription of multiple genes involved in cytokine production and T cell proliferation; atopic-like or nummular dermatitis, ichthyosiform dermatitis, urticaria, scaly psoriasiform plaques of trunk and extremities, penile rash, alopecia universalis, trachyonychia, bullae; pemphigoid nodularis (bullae and prurigo nodularis), membranous glomerulonephritis, autoimmune thyroid disease, hepatitis, exocrine pancreatitis NEJM 378:1132–1141, 2018; JAAD 55:143–148, 2006; AD 140:466–472, 2004; J Pediatr 100:731–737, 1982 Job’s syndrome (hyperimmunoglobulin E syndrome) Buckley’s syndrome – dermatitis of face, behind ears, scalp, axillae, and groin; retention of primary teeth with double rows of teeth; deep-set eyes, broad nasal bridge, wide fleshy nasal tip, prognathism, ocular hypertelorism recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract AD 140:1119–1125, 2004; Clin Inf Dis 34:1213– 1214,1267–1268, 2002; JAAD S268–269, 2002; J Pediatr 141:572– 575, 2002; NEJM 340:692–702, 1999; Curr Prob in Derm 10:41–92, 1998; Medicine 62:195–208, 1983; Pediatrics 49:59–70, 1972; Lancet 1:1013–1015, 1966 Kawasaki’s disease Kindler’s syndrome Klinefelter’s syndrome – stasis dermatitis Lipoid proteinosis – palmar dermatitis; personal observation Long arm 18 deletion syndrome Netherton’s syndrome – flexural lichenification; trichorrhexis invaginata; NK cell lymphocytopenia (immunodeficiency) BJD 178:335–349, 2018; Ped Derm 19:285–292, 2002; AD 135:823– 832, 1999; BJD 141:1097–1100, 1999; Curr Prob in Derm 10:41– 92, 1998; Ped Derm 14:473–476, 1997; Ped Derm 13:183–199, 1996; BJD 131:615–619, 1994 NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic

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self-limiting fever, polyarthritis, polyarthralgia, red plaques of face and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013 Omenn’s syndrome Acta Derm 782:71, 1988; presents in neonatal period with atopic-like dermatitis Powell syndrome – X-linked, intractable diarrhea, autoimmune polyendocrinopathy, dermatitis, hemolytic anemia Am J Med Genet 66:378–398, 1996 Rapp-Hodgkin hypohidrotic ectodermal dysplasia – autosomal dominant; alopecia of wide area of scalp in frontal to crown area, short eyebrows and eyelashes, coarse wiry sparse hypopigmented scalp hair, sparse body hair, scalp dermatitis, ankyloblepharon, syndactyly, nipple anomalies, cleft lip and/or palate; nails narrow and dystrophic, small stature, hypospadius, conical teeth and anodontia or hypodontia; distinctive facies, short stature JAAD 53:729–735, 2005; Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968 Reactive arthritis syndrome – dermatitis of penis and scrotum Rook p. 2767, 1998; Arthr Rheum 24:844–849, 1981; Semin Arthritis Rheum 3:253–286, 1974 Richner-Hanhart syndrome (tyrosinemia type II) Curr Prob in Derm 10:41–92, 1998 Say-Barber syndrome – short stature, microcephaly, large ears, flexion contractures, decreased subcutaneous fat; dermatitis in infancy with transient hypogammaglobulinemia Am J Med Genet 86:165–167, 1999 SAM syndrome – severe dermatitis, multiple allergies, metabolic wasting, palmoplantar keratoderma – autosomal recessive; mutation in Dsgl-1 BJD 17 4:444–448, 2016 Schopf-Schulz-Passarge syndrome – eyelid cysts (apocrine hidrocystoma), palmoplantar keratoderma (plantar dermatitis), hypotrichosis, decreased number of teeth, brittle and furrowed nails AD 140:231–236, 2004; BJD 127:33–35, 1992; JAAD 10:922–925, 1984; Birth Defects XII:219–221, 1971 Schwachman’s syndrome – neutropenia, malabsorption, failure to thrive; generalized xerosis, follicular hyperkeratosis, widespread dermatitis, palmoplantar hyperkeratosis Ped Derm 9:57–61, 1992; Arch Dis Child 55:531–547, 1980; J Pediatr 65:645–663, 1964 Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes, congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321–327, 1996 Spondyloepimetaphyseal dysplasia, eczema, and hypogammaglobulinemia Clin Dysmorphol 8:79–85, 1999 Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – dermatitis, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation Ped Derm 32:865–866, 2015; JAAD 44:891–920, 2001; Ped Derm 14:441– 445, 1997 Wiskott-Aldrich syndrome – dermatitis of scalp, face, flexures, napkin area with petechiae and purpura; Xp11.22–11.23; WASP gene – actin polymerization Ped Derm 24:417–418, 2007; Dermatol Therapy 18:176–183, 2005; Cell Mol Life Sci 61:2361–2385, 2004; Curr Prob Derm 14:41–70, 2002; Semin Hematol 35:332–345, 1998; J Pediatr 125:876–885, 1994; Int J Dermatol 24:77–81, 1985

TOXINS Alcohol – acute alcohol consumption; dermatitis of legs, trunk, and perineal areas BJD 155:195–197, 2006

258 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Thallium – anagen effluvium JAAD 50:258–261, 2004; nausea, vomiting, stomatitis, painful glossitis, diarrhea; severe dysesthesias and paresthesias in distal extremities, facial rashes of cheeks and perioral region, acneiform eruptions of face, hyperkeratosis of palms and soles, hair loss, Mees’ lines AD 143:93–98, 2007

TRAUMA Airbag dermatitis – bizarre shapes of erythema and dermatitis resembling factitial dermatitis JAAD 33:824–825, 1995 Radiation dermatitis JAAD 54:28–46, 2006 Radiation recall Spinal cord injury – nummular dermatitis below the level of injury AD 83:379–385, 1961 Thermal burn – personal observation

VASCULAR DISEASES Eczematoid pigmented purpuric eruption Infantile hemangioma with arrested growth – overlying dermatitis Ped Derm 35:261–262, 2018 Lymphostasis verrucosa cutis – personal observation Macular arteritis Am J Dermatopathol 30:145–149, 2008 Port wine stain with overlying dermatitis Ped Derm 24:376–379, 2007; BJD 144:1269–1270, 2001; port wine stain with thick lichenified appearance JAAD 67:1214–1219, 2012 Post-phlebitic syndrome – pain, edema, night cramps, hemosiderin deposition, dermatitis Phlebology 11:2–5, 1996 Saphenous vein graft donor site dermatitis Arch Surg 129:609, 1993 Vasculitis simulating eczematous dermatitis – with C2 deficiency Acta DV 67:265–7, 1987

ulcers, lungs/liver/spleen, defect in NADPH oxidase system; including NADPH, phagocyte cytochrome b, and cytosolic proteins; membrane-associate NADPH oxidase system fails to produce superoxide and other toxic oxygen metabolites; Staphylococcus aureus, Klebsiella, Pseudomonas, Escherichia coli, Serratia, Aspergillus, Candida, Cryptococcus, Nocardia DiGeorge’s syndrome (may be same as velocardiofacial syndrome) – autosomal dominant or sporadic; seborrheic dermatitis, atopic dermatitis; developmental defects of 3rd and 4th pharyngeal pouches, congenital thymic aplasia, neonatal tetany due to absence of parathyroids, cardiac anomalies (truncus arteriosus), short philtrum, low-set malformed ears, hypertelorism, increased susceptibility to Candida, viral, and Pneumocystis carinii infections, loss of portion of proximal long arm of chromosome 22 DOCK8 deficiency syndrome (dedicator of cytokinesis 8 gene) (aka autosomal recessive hyper-IgE syndrome) DOCK8 – involved in T cell polarization and activation; atypical guanine exchange factor; interacts with Rho GTPases (CDC42 AND RAC) which mediate actin cytoskeletal reorganization; hematologic stem cell homing and mobilization – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; warts, widespread dermatitis (atopic dermatitis-like (24% at birth; Job’s 81% dermatitis at birth), asthma, cutaneous staphylococcal abscesses; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation AD 148:79–84, 2012; infantile facial dermatitis Ped Derm 36:693–696, 2019 GATA2 disease – granulomatous dermatitis with lupoid facial lesions BJD 178:781–785, 2018; persistent HPV infection; non-tuberculous mycobacterial infection

Venous stasis dermatitis

Graft vs. host disease, pediatric – red macules or folliculocentric papules of face, ears, palms and soles, periungual areas, upper back and neck AD 143:67–71, 2007

DERMATITIS, FACIAL, PEDIATRIC

Jung’s syndrome (antihistamine responsive immunodeficiency) – atopic dermatitis, pyoderma, folliculitis, blepharitis with defective leukocyte and lymphocyte function Lancet ii:185–187, 1983

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Airborne contact dermatitis – beak sign Dermatitis 25:97–98, 2014; chlorhexidine Ped Derm 36:540–541, 2019

Juvenile rheumatoid arthritis – Still’s disease; evanescent rash; persistent pruritic papules and plaques; urticarial and urticarial-like rash, vesiculopustular eruptions, edema of the eyelids, widespread non-pruritic persistent erythema Medicine 96:e6318, 2017

Allergic contact dermatitis, including connubial (mother to infant) dermatitis; fragrance Dermatitis 20:55–56, 2009; allergic contact dermatitis to nickel with id reaction – follicular facial dermatitis Ped Derm 28:276–280, 2011; baby wipes – methylisothiazolinone Pediatr 133:e434–438, 2014

Linear IgA disease (chronic bullous disease of childhood) – personal observation

Atopic dermatitis and transient hypogammaglobulinemia Ped Derm 29:73–78, 2012

Pemphigus foliaceus – blisters, crusts, and erosions JAAD:S187–189, 2003

Bare lymphocyte syndrome – form of severe combined immunodeficiency syndrome Ann NY Acad Med 1356:90–106, 2015;

SAM syndrome – severe dermatitis (facial, especially perioral), palmoplantar keratodermas, multiple allergies, metabolic wasting; mutation in DSP gene (desmoplakin) J Allergy Clin Immunol 136:1268–1276, 2015; monoallelic mutation in DSG1 Ped Derm 37:576–578, 2020; BJD 179:755–757, 2018; BJD 172:257–261, 2015

Bruton’s hypogammaglobulinemia – atopic-like dermatitis; CARD 11 mutation; severe atopic dermatitis J Allergy Clin Immunol 143:1482– 1495, 2019; dermatomyositis-like syndrome C3 deficiency – recurrent infections, vasculitis, LE; C3 inactivator deficiency – dermatitis early in infancy Chronic granulomatous disease – X-linked or autosomal recessive, seborrheic dermatitis-like changes, Xp21 (distal end of Xp), localized pyodermas, abscesses, granulomas, perioral and intraoral

Lupus erythematosus – neonatal LE NEJM 370:958, 2014; JAAD 40:675–681, 1999; Clin Exp Rheumatol 6:169–172, 1988; discoid lupus erythematosus Ped Derm 15:439–442, 1998

Severe combined immunodeficiency syndrome Wiskott-Aldrich syndrome – thrombocytopenia, recurrent infections, atopic dermatitis, autoimmunity, malignancy Ann NY Acad Sci 1285:26–43, 2013

Dermatitis, Facial, Pediatric X-linked hypogammaglobulinemia (agammaglobulinemia) Curr Prob in Derm 10:41–92, 1998; J Allergy 33:406–411, 1962 X-linked immunodeficiency with hyper-IgM – atopic dermatitis-like rash

CONGENITAL LESIONS Collodion baby Exfoliation of the newborn Toxic erythema of newborn

DRUG-INDUCED DRESS syndrome Ped Derm 36:324–329, 2019

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Tinea versicolor Trichodysplasia spinulosa – polyoma virus Ped Derm 27:507–513, 2010

INFILTRATIVE DISORDERS Langerhans cell histiocytosis – cutaneous findings include crops of red-brown or red-yellow papules, vesicopustules, erosions, scaling, and seborrheic dermatitis-like papules, petechiae, purpura, solitary nodules, bronze pigmentation, lipid infiltration of the eyes, white plaques of the oral mucosa, onycholysis, and onychodystrophy Curr Prob Derm VI Jan/Feb 1994; Clin Exp Derm 11:183–187, 1986; JAAD 13:481–496, 1985; purpuric papules in the neonate; Letterer-Siwe disease JAAD 18:646–654, 1988

Multiple drug allergies Retinoid (isotretinoin) dermatitis

EXOGENOUS AGENTS

INFLAMMATORY DISEASES Stevens-Johnson syndrome Toxic epidermal necrolysis

Giant hogweed Irritant contact dermatitis Lemons – furocoumarins Lime phototoxicity (phytophotodermatitis) Wounds 29:E118–124, 2017

INFECTIONS AND INFESTATIONS AIDS – atopic dermatitis-like eruption; dermatitis of HIV disease in children JAAD 20:1130, 1989 Candidiasis, including chronic mucocutaneous candidiasis Demodex folliculitis – demodicidosis – facial dermatitis, seborrheiclike dermatitis, perioral dermatitis, acneiform papulopustular lesions Ped Derm 36:651–654, 2019; papular facial dermatitis in children with acute lymphoblastic leukemia Ped Derm 22:407–411, 2005 Dermatophytid reaction Ped Derm 32:635–640, 2015 Gianotti-Crosti syndrome – personal observation Herpes simplex infection – eczema herpeticum Human T-lymphotrophic virus type 1-associated infective dermatitis – chronic relapsing dermatitis; severe red and exudative dermatitis with scaling and crusting of scalp, forehead, eyelids, paranasal area, neck, retroauricular, external ear, axillae, groin; chronic watery nasal discharge, crusting of anterior nares, blepharoconjunctivitis; generalized fine popular rash with lymph nodes; onset of rash at age 2 years; most common form of transmission is breast feeding; harbinger of development of adult T-cell lymphotropic leukemia and HTLV-1 associated myelopathy (HAM)/tropical spastic paralysis (TSP); Jamaica, Senegal, Brazil (endemic areas) JAAD 64:152–160, 2011; Proc Natl Acad Sci USA 77:7415–7419, 1980; BJD 79:229–236, 1967; BJD 78:93–100, 1966 Impetigo contagiosa Molluscum contagiosum – dermatitis surrounding the mollusca (molluscum dermatitis) AD 74:344–348, 1956

METABOLIC Acrodermatitis enteropathica – autosomal recessive, mutation SCL39A4; encodes ZIP; acquired zinc deficiency; periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche JAAD 56:116–124, 2008 Biotinidase deficiency – combination of eczematous dermatitis and neurologic symptoms Celiac disease – atopic dermatitis-like eruption Lancet i:115–117, 1976 Cystic fibrosis, heterozygote Lancet i:990–991, 1976 Hartnup’s disease Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999 Holocarboxylase synthetase deficiency Ped Derm 28:333–334, 2011 Kwashiorkor – enamel paint change; may resemble atopic dermatitis on the face; red brown scaly plaques JAAD 21:1–30, 1989 Lysinuric protein intolerance – autosomal recessive; defect in membrane transport of cationic amino acids (lysine, arginine, ornithine); hyperammonemia; dermatitis resembling neonatal lupus Lancet 363:1038, 2004; Eur J Pediatr 160:5223, 2001 Methylmalonic acidemia cobalamin C type AD 133:1563–1566, 1997 Multiple carboxylase deficiency (biotin-responsive) – pyruvate carboxylase, propionyl-coenzyme A carboxylase, and 3-methylcrotohyl-­CoA carboxylase; accumulation of urinary organic acids; neonatal – holocarboxylase synthetase deficiency; juvenile or late-onset from – biotinidase deficiency Ped Derm 21:231–235, 2004; Ped Derm 16:95–102, 1999 Pellagra Phenylketonuria Curr Prob in Derm 10:41–92, 1998

Parvovirus B19 (erythema infectiosum) – “slapped cheeks” Staphylococcal scalded skin syndrome Syphilis – congenital syphilis Ped Derm 23:121–123, 2006; secondary Tinea faciei, including tinea incognito Arch Ophthalmol 129:306– 309, 2011

NEOPLASTIC DISEASES Hydroa vacciniforme-like lymphoproliferative disorder, Epstein-Barr virus-related JAAD 81:534–540, 2019 Leukemia cutis – aleukemic juvenile myelomonocytic leukemia

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Transient myeloproliferative disorder associated with mosaicism for trisomy 21 – pustular, papulovesicular, vesiculopustular rash, facial dermatitis JAAD 54:S62–64, 2006; NEJM 348:2557–2566, 2003

PHOTODERMATITIS Actinic prurigo The Dermatologist May, 2015, pp47–48, 50, 2015; BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981

PRIMARY CUTANEOUS DISEASE Atopic dermatitis – infra-auricular fissure JAAD 66:1009–1010, 2012; HIV photodermatitis – photolichenoid dermatitis Cutis 104:242–244, 2019; chronic actinic dermatitis Ann Acad Med Singapore 30:664– 667, 2001 Bullous congenital ichthyosiform erythroderma Epidermolytic hyperkeratosis Exfoliative dermatitis/exfoliative erythroderma J Dermatol 26:507– 511, 1999; Clin Dermatol 37:88–98, 2019

AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964 Bloom’s syndrome CANDLE syndrome Dubowitz syndrome – autosomal recessive, microcephaly, sloping forehead, telecanthus, erythema and scaling of face and extremities in infancy, ichthyosiform eruption, sparse blond scalp and arched eyebrow hair, dysplastic low set ear pinnae, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities; syndactyly, cryptorchidism, hypospadius, developmental delay, transitory short stature, hyperactive behavior, blepharophimosis, ptosis of the eyelids, epicanthal folds, broad nose, palate anomalies, micrognathia, and severe atopic dermatitis Ped Derm 22:480–481, 2005; Am J Med Genet 63:277–289, 1996; Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959– 964, 1993; Eur J Pediatr 144:574–578, 1986; Am J Med Genet 4:345–347, 1979; J Med Genet 2:12–17, 1965 Goltz’s syndrome Hereditary acrokeratotic poikiloderma of Weary – vesiculopustules of hands and feet at age 1–3 months which resolve; widespread atopic dermatitis-like dermatitis; diffuse poikiloderma with striate and reticulate atrophy; keratotic papules of hands and feet, elbows and knees; autosomal dominant AD 103:409–422, 1971

Pityriasis rubra pilaris – seborrheic dermatitis facial and scalp rash in infants BJD 157:202–204, 2007;

Hyper IgE syndrome (Job’s syndrome) (Buckley’s syndrome) – dermatitis of face, scalp, axillae, and groin; recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract; papular, pustular, excoriated dermatitis of scalp, buttocks, neck, axillae, groin; furunculosis; growth failure; dermatitis of face, behind ears, scalp, axillae, and groin; recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract; STAT3 mutations J Pediatr 141:572–575, 2002; NEJM 340:692– 702, 1999; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983; Lancet 1:1013– 1015, 1966 Ped Derm 30:621–622, 2013; NEJM 357:1608–1619; JAAD 54:855–865, 2006; AD 140:1119–1125, 2004; J Pediatr 141:572–575, 2002; Curr Prob in Derm 10:41–92, 1998; Medicine 62:195–208, 1983; Pediatrics 49:59–70, 1972; Lancet 1:1013– 1015, 1966

Progressive symmetric erythrokeratoderma

Kawasaki’s disease

Psoriasis BJD 135:501, 1996

KID syndrome – keratosis, ichthyosis, deafness syndrome – fixed orange, symmetrical hyperkeratotic plaques of scalp, ears, and face with perioral rugae; aged or leonine facies; erythrokeratoderma-like; later hyperkeratotic nodules develop Ped Derm 17:115–117, 2000; Ped Derm 13:105–113, 1996

Keratosis lichenoides chronica Ped Derm 29:511–512, 2012 Leiner’s disease Lichen striatus Ped Derm 30:364–366, 2013 Non-bullous congenital ichthyosiform erythroderma Papular urticaria – personal observation Periorbital dermatitis (periorbital variant of perioral dermatitis) (granulomatous perioral dermatitis) – idiopathic or topical corticosteroid-­associated including facial Afro-Caribbean childhood eruption (FACE) BJD 91:435–438, 1976; granulomatous perioral dermatitis – personal observation Pityriasis lichenoides chronica Pityriasis rosea

Seborrheic dermatitis – pustular seborrheic dermatitis Vorner’s palmoplantar keratoderma

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis Ped Derm 21:205–211, 2004

SYNDROMES Ataxia telangiectasia Bazex-Dupre-Christol-like syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Ped Derm 25:112–113, 2008; Ped Derm 23:286–290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999;

Netherton’s syndrome Rothmund-Thomson syndrome Wiskott-Aldrich syndrome – dermatitis of scalp, face, flexures, napkin area with petechiae and purpura; Xp11.22-11.23; WASP gene – actin polymerization Ped Derm 24:417–418, 2007; Cell Mol Life Sci 61:2361–2385, 2004; Semin Hematol 35:332–345, 1998; J Pediatr 125:876–885, 1994; Int J Dermatol 24:77–81, 1985 Xeroderma pigmentosum

TRAUMA Jelly fish envenomation Eur J Emerg Med 25:434–439, 2018 Lip lickers dermatitis The Clinical Management of Itching; Parthenon; p. 76, 2000 Radiation reaction

Dermatitis, Periorbital

VASCULAR LESIONS

EXOGENOUS AGENTS

Vasculitis – acute hemorrhagic edema of infancy

Irritant contact dermatitis JAAD 47:755–765, 2002

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Food – rice Allerg Immunopathol 20:171–172, 1992

DERMATITIS, PERIORBITAL  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis JAAD 47:755–765, 2002; protein contact dermatitis; eyeglass frames; nail cosmetics, eyedrops, fragrance, preservatives; airborne thiuram dermatitis Contact Dermatitis 73:321–322, 2015

Recurrent facial eczema due to "strike anywhere" matches phosphorus sesquisulphide BJD 106:477, 1982

INFECTIONS AND INFESTATIONS Anthrax Cat scratch disease Chlamydia Coccidioides immitis Ann Ophthalmol 20:391–393, 1988

Dermatomyositis JAAD 47:755–765, 2002

Cutaneous larva migrans

Graft vs. host reaction AD 126:1324–1329, 1990; sclerodermatous graft vs. host reaction – periorbital papules JAAD 26:49–55, 1992; periorbital lichenoid chronic graft vs. host reaction AD 134:602–612, 1998

Demodex folliculorum – periorbital papular dermatitis JAAD 60:453–462, 2009

Juvenile rheumatoid arthritis (Still’s disease) Lupus erythematosus – SLE JAAD 26:334, 1992; discoid LE (eyelid plaques) AD 129:495, 1993; bullous LE; lupus profundus JAAD 24:288, 1991; neonatal LE (raccoon eyes) JAAD 40:675–681, 1999; Clin Exp Rheumatol 6:169–172, 1988 Pemphigus vulgaris, foliaceus – erythema and erosions JAAD 33:312–315,1995 Progressive systemic sclerosis and linear scleroderma JAAD 7:541–544, 1982 Urticaria (systemic, contact, physical) – eyelid dermatitis JAAD 47:755–765, 2002

Dermatophytosis – Microsporum canis Ann Ophthalmol 20:391– 393, 1988 Ecthyma gangrenosum BJD 148:121, 2003 Epidemic keratoconjunctivitis Herpes simplex virus – primary infection; chronic Herpes zoster – including post-zoster dysesthesias HTLV-1 infection – infective dermatitis of scalp, eyelid margins, perinasal skin, retro-auricular areas, axillae, groin; generalized papular dermatitis Lancet 336:1345–1347, 1990; BJD 79:229–236, 1967; BJD 78:93–100, 1966 Impetigo Insect bites Intraocular infections

DRUG-INDUCED

Jellyfish envenomation Leishmaniasis

Atacurium

Lepidopterism

Augmentin drug eruption

Leprosy

Calcium channel blockers JAAD 21:132–133, 1989

Lyme disease

Contrast medium Clin Radiol 40:108, 1989

Lymphogranuloma venereum

Corticosteroids – topical corticosteroid periorbital dermatitis

Malaria

Dilantin AD 114:1350, 1978

Measles

Docetaxel BMJ Case Rep July 21, 2019

Molluscum contagiosum Ann Ophthalmol 20:391–393, 1988

Erythropoietin

Mucormycosis AD 122:329–334, 1986

Fixed drug eruption

Mycobacterium tuberculosis – scrofuloderma

Imatinib Int J Dermatol 57:332–338, 2018

Myiasis

Interleukin 4

Necrotizing fasciitis, bilateral periorbital AD 140:664–666, 2004

Mannitol

Papular urticaria

Methotrexate periorbital radiation recall Ann Pharmacother 45:133, 2011

Russell’s viper bite

Methylprednisolone Am J Ophth 113:588–590, 1992 Nifedipine Am J Cardiol 55:1445, 1985 Phenylephrine Contact Dermatitis 53:298–299, 2005

Scabies – crusted (Norwegian) scabies Ped Derm 17:410–414, 2000 Scarlet fever Sparganosis

Post-influenza vaccination Can Med Assoc J 116:724, 1977

Sporotrichosis – secondary to cat scratch; periorbital papules Ped Derm 28:457–458, 2011; AD 118:429–431, 1982

Rifampin

Syphilis – primary (chancre), secondary

Steroid rosacea

Staphylococcal scalded skin syndrome

Toxic epidermal necrolysis/Stevens-Johnson syndrome

Verrucae planae (flat warts)

262 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFILTRATIVE DISEASES Amyloidosis, including macular amyloidosis with periorbital hyperpigmentation Clin Exp Dermatol 8:195–197, 1983 Colloid milium

Lymphoma, including cutaneous T cell lymphoma (CTCL) JAAD 47:755–765, 2002 Melanoma – amelanotic melanoma BMJ Case Rep March 29, 2018 Merkel cell tumor

Langerhans cell histiocytosis

Metastatic cancer – eyelid enlargement, breast cancer JAAD 37:362–364, 1997; mask like metastases, gastric and breast carcinomas Am J Dermatopathol 32:9–14, 2010

Mucinosis, cutaneous

Myeloma – cutaneous crystalline deposits AD 130:484–488,1994

Orbital pseudotumor Ann Allergy 69:101–105, 1992

Periorbital cutaneous myxomas JAAD 34:928–930, 1995

Scleromyxedema JAAD 928–930, 1996

Sebaceous gland carcinoma

Xanthoma disseminatum – periorbital papules JAAD 15:433–436, 1991

Primary sweat gland carcinoma

Eosinophilic or basophilic granulomas (pseudotumor of orbit)

Syringomas Trichoepithelioma

INFLAMMATORY DISEASES Erythema multiforme Morbihan’s disease – chronic facial edema Dermatol Online J Dec 15, 2012

PHOTODERMATITIS Chronic actinic dermatitis

Neutrophilic eccrine hidradenitis JAAD 38:1–17,1998; JAAD 131:1141–1145, 1995; JAAD 28:775, 1993

Phytophotodermatitis – Ruta graveolens, plant known as rue Ann Emerg Med 72:25–83, 2018

Orbital myositis and giant cell myocarditis JAAD 35:310–312, 1996

Piroxicam (Feldene) photodermatitis

Sarcoid Ann DV 144:440–443, 2017; AD 118:356–357, 1982; Parinaud’s oculoglandular syndrome

Polymorphic light eruption

METABOLIC DISEASES

PRIMARY CUTANEOUS DISEASES

Acrodermatitis enteropathica

Acne rosacea – eyelid dermatitis JAAD 47:755–765, 2002; JAAD 37:346–348, 1997; AD 121:87, 1985

Fabry’s disease Arch Ophthal 74:760, 1965

Quinidine photo-lichen planus

Hartnup’s disease Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; presenting in adulthood Clin Exp Dermatol 19:407–408, 1994

Acne vulgaris

Holocarboxylase synthetase deficiency – periorbital and periorificial erythema and/or dermatitis, intertriginous erythema Ped Derm 28:333–334, 2011

Angiolymphoid hyperplasia with eosinophilia Ped Derm 15:91–96, 1998; Ann Allergy 69:101–5, 1992

Alopecia mucinosa

Type B Niemann-Pick disease Metab Ped Syst Ophthal 15:16–20, 1992

Atopic dermatitis JAAD 47:755–765, 2002; periorbital crusting in atopic dermatitis due to group A beta hemolytic streptococcus; herpetiform lesions Ped Derm 28:230–234, 2011

Xanthelasma

Blepharitis granulomatosa AD 120:1141, 1984

Vitamin B2 (riboflavin) deficiency – dermatitis around nose, eyes, ears, and genitals (oro-oculogenital syndrome) Clinics in Derm 17:457–461, 1999; AD 112:70–72, 1976

Epidermolysis bullosa – Herlitz junctional EB and junctional EB mitis – periorbital erosions Granuloma annulare Lichen planus of eyelids – heliotrope JAAD 27:638, 1992

NEOPLASTIC DISEASES Angiosarcoma of face and scalp (Wilson-Jones angiosarcoma) JAAD 38:143–175, 1998 Atypical lymphoid hyperplasia JAAD 37:839–842, 1997 Basal cell carcinoma Benign and malignant ectodermal and mesodermal tumors (orbital tumors)

Lichen sclerosus et atrophicus Lichen simplex chronicus – eyelid dermatitis JAAD 47:755–765, 2002 Periorbital dermatitis (periorbital variant of perioral dermatitis) – idiopathic or topical corticosteroid-associated, including facial Afro-­ Caribbean childhood eruption (FACE) BJD 91:435–438, 1976 Psoriasis JAAD 47:755–765, 2002

Bowen’s disease

Rosacea – lupus miliaris disseminate faciei J Eur Acad Dermatol Venereol 19:470–473, 2005

Carcinoid syndrome

Seborrheic dermatitis JAAD 47:755–765, 2002

Embryonal rhabdomyosarcoma

Vitiligo and sunburn

Epidermal inclusion cyst Eruptive hidradenoma – papules Cutis 46:69–72, 1990 Juvenile xanthogranuloma JAAD 14:405–411, 1986

PSYCHOCUTANEOUS

Kaposi's sarcoma

Delusions of parasitosis

Leukemia, including HTLV-1 – papules

Factitial dermatitis

Dermatitis, Periorificial

SYNDROMES Anhidrotic ectodermal dysplasia Carcinoid syndrome Fabry’s disease

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dermatitis 26:192–194, 2015; allergic contact dermatitis to anethole (flavoring agent of toothpaste) Dermatitis 28:219–220, 2017 Amicrobial pustulosis associated with autoimmune disease treated with zinc BJD 143:1306–1310, 2000

Familial sea blue histiocytosis

Chronic granulomatous disease – impetiginized perioral dermatitis JAAD 36:899–907, 1997

Hypereosinophilic syndrome

Dermatomyositis – personal observation

Kawasaki’s disease

Dermatitis herpetiformis

Lipoid proteinosis

Hyper IgE syndrome Am J Dis Child 143:1038–1041, 1989

Melkersson-Rosenthal syndrome

IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, pemphigoid nodularis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash; thyroid dysfunction, diabetes mellitus, hepatitis, nephritis, onychodystrophy, alopecia universalis; mutations in FOXP3 (forkhead box protein 3) gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia JAAD 73:355–364, 2015; BJD 160:645–651, 2009; ichthyosiform eruptions Blood 109:383–385, 2007; BJD 152:409–417, 2005; NEJM 344:1758– 1762, 2001; alopecia areata AD 140:466–472, 2004

NAME/LAMB syndromes Netherton’s syndrome Neurofibromatosis Sjogren’s syndrome – eyelid dermatitis JAAD 47:755–765, 2002 SLY syndrome Sturge-Weber syndrome Sweet’s syndrome JAAD 24:140–141, 1991

TOXINS Alkali burn Eosinophilia myalgia syndrome

Linear IgA disease (chronic bullous disease of childhood) – perioral, perivulvar annular polycyclic bullae Ped Derm 15:108–111, 1998; Ped Derm 11:139–144, 1994 Lupus erythematosus, neonatal – personal observation

TRAUMA Asphyxia – facial congestion, facial edema, cyanosis, periorbital or conjunctival petechiae JAAD 64811–824, 2011 Physical trauma Valsalva maneuver – periorbital purpuric eruption

Pemphigus foliaceus Ann DV 126:41–43, 1999 Pemphigus vulgaris, including peristomal pemphigus – personal observation Pemphigus vegetans – personal observation SAM syndrome – severe dermatitis, allergies, and metabolic wasting; perioral accentuation to dermatitis Ped Derm 37:576–578, 2020

VASCULAR DISEASES Disseminated intravascular coagulation Br J Ophth 72:347–379, 1988 Granulomatosis with polyangiitis

CONGENITAL LESIONS Urachal sinus presenting as periumbilical psoriasiform dermatitis BJD 157:419–420, 2007

Hemangiomas Neonatal hemangiomatosis Pyogenic granuloma Recurrent cutaneous necrotizing eosinophilic vasculitis Sem Derm 14:106–110, 1995; AD 130:1159–1166, 1994

DRUGS Chemotherapy – zinc deficiency BJD 135:659–660, 1996

Thrombotic thrombocytopenic purpura

Corticosteroid, topical – perioral dermatitis JAAD 54:1–15, 2006; Int J Derm 26:649, 1987; inhaled budesonide – periorificial dermatitis around mouth and eyes Ped Derm 28:596–597, 2011; rosacea JAAD 54:1–15, 2006

DERMATITIS, PERIORIFICIAL

Fixed drug eruption

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – perioral dermatitis from toothpaste, dental fillings; epoxy diacrylates JAAD 38:116–120, 1998; apple – perioral urticarial dermatitis JAAD 53:736–737, 2005; perianal dermatitis from local anesthetics, fragrances, antifungals, topical corticosteroids peristomal ulcers AD 142:1372–1373, 2006; vulvar or perianal dermatitis – allergic contact dermatitis to Cottonelle moist toilet paper (methylchlorisothiazolinone/methylisothiozolinone) AD 146:886–890, 2010; benzophenone sunscreen agents – perioral

Hepatitis B vaccine – necrolytic acral erythema; psoriasiform dermatitis, acral erythema and scale, cheilitis, verrucous papules of eyelids and around nose BJD 171:1255–1256, 2014 Nicorandil – peristomal ulcers, perianal ulcers; bowel perforation BJD 167:1048–1052, 2012

EXOGENOUS AGENTS Benzocaine – erosive papulonodular vulvar dermatitis JAAD 55:S74–80, 2006 Ecstasy Dermatology 197:171–173, 1998

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Irritant contact dermatitis – peristomal ulcers AD 142:1372–1373, 2006; urostomy JAAD 19:623–628, 1988; Scand J Urol Nephrol 13:201–204, 1979; dentifrice irritant contact dermatitis – personal observation Suture granulomas – peristomal ulcers AD 142:1372–1373, 2006 Tartar control dentifrice dermatitis – perioral JAAD 22:1029–1032

INFECTIONS AIDS, childhood – atopic dermatitis-like eruption acrodermatitis enteropathica-like dermatitis J Pediatr 108:426–428, 1986; zinc deficiency AD 128:415–417, 1992

Syphilis – secondary; congenital syphilis Ped Derm 23:121–123, 2006; periorificial nodules – malignant secondary syphilis JAMA Derm 152:829–830, 2016; AD 99:70–73, 1969; BJD 9:11–26, 1897 Tinea incognito, treated with topical corticosteroids Cutis 77:293– 296, 2006; tinea faciei – around nasal vestibule; Trichophyton mentagrophytes var erinacei (hedgehog) Ped Derm 29:409–413, 2012; Ped Derm 28:210–212, 2011 Yaws – secondary (daughter yaws, pianomas, framboesiomas) – small papules which ulcerate, become crusted; resemble raspberries; periorificial (around mouth, nose, penis, anus, vulva); extend peripherally (circinate yaws); hyperkeratotic plantar plaques (crab yaws); periungual JAAD 29:519–535, 1993

Calymmatobacterium granulomatis (granuloma inguinale) Candidiasis, including chronic mucocutaneous candidiasis; peristomal ulcers AD 142:1372–1373, 2006; perleche Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of fingers, palmar erythema, red papules of ears, red papules of antecubital fossa, perioral papulovesicles, vesicles of posterior pharynx; crusted papules of scalp, ears, and face; purpuric targetoid painful vesicular lesions of hands and feet, arthritis, fissured scrotum JAMA Derm 149:1419–1421, 2013; JAAD 69:736–741, 2013; Coxsackie A16 – hand, foot, and mouth disease; blisters and vesicopustules; perioral dermatitis Cutis 102:353–356, 2018 Deep fungal infections – peristomal ulcers AD 142:1372–1373, 2006 Demodex folliculitis – papular facial dermatitis in children with acute lymphoblastic leukemia Ped Derm 22:407–411, 2005; demodicidosis in adults – perioral papular dermatitis JAAD 60:453–462, 2009; Ann DV 113:1047–1058, 1986 Green shield bug (Palomena prasina) – perioral bullae BJD 119:121–125, 1988

INFILTRATIVE DISEASES Langerhans cell histiocytosis Xanthoma disseminatum – perioral papules; eyelid papules; scrotal papules; intertrigo BJD 170:1177–1181, 2014

INFLAMMATORY DISEASE Crohn’s disease – peristomal ulcers AD 142:1372–1373, 2006 Erythema multiforme Ped Derm 24:334–336, 2007 Hidradenitis suppurativa Hirschsprung disease – perianal papulonodular dermatitis Ann DV 123:549–551, 1996 Pyoderma gangrenosum – peristomal ulcers – JAAD 75:931–939, 2016; J Drugs in Dermatol 10:1059–1061, 2011; BJD 161:1206– 1207, 2009; AD 143:669–670, 2007; BJD 157:618–619, 2007; AD 142:1372–1373, 2006 Pyoderma vegetans Hautarzt 35:132–137, 1984

Hand, foot, and mouth disease – personal observation

Sarcoid

Atypical hand, foot, and mouth disease – Coxsackie A6; hemorrhagic bullae of palms, dorsal hands, and fingers; perioral papulovesicles JAAD 76:722–729, 2017

Stevens-Johnson syndrome – personal observation

Herpes simplex virus – herpes stomatitis Ped Derm 20:289–294, 2003; Drugs Aging 19:503–514, 2002; eczema herpeticum Cutis 73:301, 317, 2004; peristomal ulcers AD 142:1372–1373, 2006 Impetigo Leishmaniasis – post kala azar dermal leishmaniasis – perioral papules and nodules BJD 157:1032–1036, 2007 Mycobacterium tuberculosis – tuberculosis orificialis – perioral crusted vegetative plaque Am J Clin Dermatol 3:319–328, 2002 Non-tuberculous mycobacteria – peristomal ulcers AD 142:1372– 1373, 2006 Paracoccidioidomycosis – oral and perioral crusted granulomatous plaques JAAD 53:931–951, 2005 Parvovirus B19 infection – generalized petechial eruption with perioral accentuation JAAD 52:S109–113, 2005; Clin Inf Dis 35:1558–1561, 2002 Perianal streptococcal cellulitis Pseudomonas – ecthyma gangrenosum in the neonate Pyoderma Staphylococcal scalded skin syndrome Staphylococcus aureus – peristomal ulcers AD 142:1372–1373, 2006

Ulcerative colitis – peristomal ulcers AD 142:1372–1373, 2006

METABOLIC Acrodermatitis dysmetabolica – ornithine transcarbamylase deficiency, maple syrup urine disease, methylmalonic acidemia, propionic acidemia, glutaric aciduria type 1, phenylketonuria – arginine and isoleucine deficiency from restricted diet in all of the above Ped Derm 28:457–458, 2011 Acrodermatitis enteropathica or acquired zinc deficiency – autosomal recessive; zinc is metal moiety of enzymes such as alkaline phosphatase (results in low serum alkaline phosphatase), alcohol dehydrogenase, digestive enzymes; periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche; pustulous paronychia Acta DV 23:127–169, 1942; mutation in SLC39A4 solute carrier family 39 (zinc transporter) member 4 gene encodes histidine-rich protein Hzip4 (zinc transporter protein; member of ZIP (zinc/iron-regulated transporter-like protein) Ped Derm 28:735–736, 2011; Ped Derm 28:697–700 2011; Ped Derm 27:395–396, 2010; BJD 161:184–186, 2009; Cutis 81:314, 324–326, 2008; JAAD 56:116–124, 2008;; BJD 157:386–387, 2007; Ped Derm 19: 426–431, 2002; Ped Derm 19:180–182, 2002; AD 116:562–564, 1980; J Inorg Biochem 12:71–78, 1980; Dermatologica 156:155–166, 1978; Int J Derm 17:380–387, 1978; Lancet 2:399–400, 1974; Lancet 1:676–677, 1973; Acta DV 23:127–169, 1942; Acta DV 17:513–546, 1936; zinc deficiency in

Dermatitis, Periorificial premature infants Ped Derm 27:380–383, 2010; transient neonatal zinc deficiency – mutation in SLC30A2; ZnT-2 protein dysfunction – transporter protein responsible for secreting zinc into breast milk Ped Derm 31:251–252, 2014; acquired zinc deficiency – inadequate intake, low breast milk zinc, weaning to cow’s milk, excessive losses, malabsorption, increased demand; starvation, anorexia nervosa, cystic fibrosis, liver disease, diabetes mellitus, HIV disease, chronic alcoholism, extensive burns, Crohn’s disease, sickle cell anemia, sprue, systemic malignancies, pancreatic insufficiency, renal tubular dysfunction, drugs, defect of mammary zinc secretion, blind loop syndrome, diets high in phytates and calcium, following bariatric surgery NEJM 371:67, 2014; JAAD 69:616–624, 2013; Ped Derm 24:536–540, 2007; Ped Derm 19:426–431, 2002; Ped Derm 17:337–347, 2000; Am J Dis Child 135:968–969, 1981; Down’s syndrome, congenital thymus defects Japan Medical Assoc J 47:359–364, 2004; total parenteral nutrition – zinc deficiency Dermatologica 156:175–183, 1978; Am J Clin Nutr 29:197–204, 1976; prematurity BJD 104:459–464, 1980; alcoholism Cutis 82:60–62, 2008; late acquired acrodermatitis enteropathica NEJM 352:1121, 2005 Alcoholic pancreatitis and cirrhosis – zinc deficiency Int J Dermatol 34:651–652, 1995; AD 114:937–939, 1978 Biotin deficiency, dietary – dermatitis around nose and mouth J Dermatol 32:256–261, 2005; Acta Pediatr 85:872–874, 1996 Biotinidase deficiency – autosomal recessive; pyruvate carboxylase, propionyl-coenzyme A carboxylase, and 3-methylcrotohyl-CoA carboxylase; accumulation of urinary organic acids; neonatal and infantile; neonatal – holocarboxylase synthetase deficient; seen in first 6 weeks of life; fiery red intertriginous dermatitis; infantile, juvenile, or late onset – biotinidase deficient (biotin-responsive multiple carboxylase deficiency); after 3 months of life, intertriginous rash with keratoconjunctivitis, xerosis, generalized pallor, periorificial dermatitis, alopecia, branny desquamation, and atrophic; psoriasiform, periorificial intertriginous dermatitis; diarrhea, alopecia Ped Derm 33:457–458, 2016; NEJM 304:820–823, 1981 glossitis Ped Derm 21:231–235, 2004; Ped Derm 16:95–102, 1999; Semin Dermatol 10:296–302, 1991; JAAD 9:97–103, 1983 Carbamoyl phosphate synthetase (urea cycle) deficiency (arginine deficiency) Am J Dis Child 135:437–442, 1981 Neonatal citrullinemia – autosomal recessive; deficiency of argininosuccinic acid synthetase or ornithine transcarbamylase or carbamoyl phosphate synthetase; acrodermatitis enteropathica-like rash; cutaneous lesions due to arginine deficiency JAAD 59:1–22, 2008; JAAD 46:965–967, 2002; JAAD 14:321–326, 1986; Am J Dis Child 135:437–442, 1981; J Pediatr 90:218–224, 1977; Arch Dis Child 49:579–581, 1974 Crohn’s disease – perioral papular dermatitis; with zinc deficiency J Gastroenterol 33:876–879, 1998 Cystic fibrosis – acrodermatitis enteropathica-like dermatitis AD 146:171–174, 2010; JAAD 58:S5–8, 2008; Ped Derm 17:337–347, 2000; AD 119:51–55, 1983; malnutrition-associated rash of cystic fibrosis Ped Derm 17:337–347, 2000 Essential amino acid deficiencies – isoleucine, valine, methionine, threonine; same clinical picture as acrodermatitis enteropathica Ped Derm 19:180–182, 2002 Essential fatty acid deficiency – unsaturated 18, 20 or 22 carbon chain lengths; n-6 series produces arachidonic acid from linoleic acid; EFAs are precursors of eicosanoids, influence membrane fluidity and are necessary for lamellar granule formation in epidermis; alopecia, generalized xerotic scaling and intertriginous erosions Med Hypotheses 6:277–296, 1980; AD 113:939–941, 1977; Pediatrics 31:171–192, 1963

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Gastrectomy Int J Dermatol 37:134–137, 1998 Glutaric aciduria type I Eur J Dermatol 11:244–246, 2001 Hartnup disease – autosomal recessive; defective transport of tryptophan in small intestine and kidneys; pellagra-like photosensitive eruption; cerebellar ataxia; psoriasiform red scaly plaques, generalized alopecia, widespread edema Ped Derm 23:262–265, 2006 Histidine deficiency Am J Clin Nutr 21:367–375, 1968; Pediatrics 31:786–801, 1963 Holocarboxylase synthetase deficiency – autosomal recessive; scaly eyebrows, eyelashes, scalp Ped Derm 23:142–144, 2006 Intestinal bypass procedure AD 114:1509–1511, 1978 Isoleucine deficiency – diet treatment of propionic acidemia and arginino-succinic acidemia BJD 139:488–491, 1998; JAAD 28:289, 1993; Ped Derm 9:191, 1992 Kwashiorkor – protein/amino acid deficiency – perioral dermatitis; patient has peripheral edema yet only weighs 60–80% of expected weight; patches of hypopigmentation with fine circumoral branny desquamation; extensor surfaces dry, glossy and cracked; edema starts on dorsal aspects of feet and can generalize; enamel paint spots on elbows, knees, ankles, and intertriginous areas; flaky paint describes extensive peeling with erosion and flexural fissuring; red tinge to hair; flag sign AD 137:630–636, 2001; JAAD 21:1–30, 1989; AD 123:1674–1676, 1987 Liver disease, chronic (cirrhosis) – pseudoglucagonoma syndrome BJD 101:581–587, 1979 Maple syrup urine disease – isoleucine, leucine, and/or valine deficiency; impaired degradation of branched chain amino acids; elevated leucine, isoleucine, and valine in blood, urine and tissues; erythematous scaling diaper dermatitis; periorificial and acral dermatitis, diarrhea, alopecia; widespread erythematous dermatitis during treatment with dietary restriction with diet low in branched chain amino acids Ped Derm 26:150–154, 2009; J Pediatr 124:416– 420, 1994; Am J Dis Child 147:954–956, 1993; JAAD 28:289–292, 1993; JID 86:508, 1986 Methylmalonic acidemia – deficiency of methylmalonyl coenzyme A mutase or its cofactors adenosylcobalamin (vitamin B12) and methylcobalamin; affects metabolism of four amino acids (valine isoleucine, threonine, methionine); these patients fed low protein diets limited in branched chain amino acids Ped Derm 26:150–154, 2009; Ped Derm 24:455–456, 2007; Dermatol Pediatr Lat 1:46–48, 2003; Ped Derm 16:95–102, 1999; AD 133:1563–1566, 1997; J Pediatr 124:416–420, 1994; BJD 131:93–98, 1994 Non-ketotic hyperglycinemia J Dermatol 27:604–608, 2000 Nutritional deficiency associated with anorexia nervosa AD 140:521–524, 2004 Ornithine transcarbamylase deficiency – acrodermatitis enteropathica-­like dermatitis Ped Derm 26:150–154, 2009; Ped Derm 24:394–396, 2007; JAAD 46:965–967, 2002 Pellagra – scrotal and perineal erythema; vaginal erythema BJD 164:1188–1200, 2011 Phenylketonuria – severe diaper dermatitis Ped Derm 26:150–154, 2009 Propionic acidemia (aciduria) – these patients fed low protein diets limited in branched chain amino acids Ped Derm 26:150–154, 2009; Ped Derm 16:95–102, 1999; J Pediatr 124:416–420, 1994  Pyridoxine deficiency – pyridoxal phosphate is coenzyme in tryptophan metabolism, alanine aminotransferase, apartate aminotransferase, amino acid cocarboxylases, deaminase, transulfurases, and desulfhydrase enzymes, amino butyric acid synthesis and fatty acid metabolism JAAD 15:1263–1264, 1986

266 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Tyrosinemia type II Ped Derm 17:337–347, 2000 Vitamin B1 deficiency Clinics in Derm 17:457–461, 1999 Vitamin B2 (riboflavin) deficiency – dermatitis around nose, eyes, ears, and genitals (oro-oculogenital syndrome) Clinics in Derm 17:457–461, 1999; AD 112:70–72, 1976

NEOPLASTIC DISORDERS Eccrine syringofibroadenoma – reactive peristomal eccrine syringofibroadenoma – cerebriform verrucous plaque JAAD 58:691–696, 2008 Leukemia – HTLV-1 (acute T-cell leukemia) – perioral, perinasal, retroauricular rashes JAAD 49:979–1000, 2003 Lymphoma – cutaneous T-cell lymphoma; perioral dermatitis Clin Exp Dermatol 17:132–134, 1992; primary cutaneous peripheral T-cell lymphoma BJD 164:677–679, 2011; lymphoma – zinc deficiency Ann DV 120:767–769, 1993 Metastases – peristomal red plaque with ulcers – metastatic adenocarcinoma of the rectum AD 142:1372–1373, 2006 Myelodysplastic syndrome with cutaneous granulomas – personal observation Porokeratosis of Mibelli – perioral erythematous plaque JAMA Derm 151:85–86, 2015 Syringomas, eruptive SKIN Med 10:186–187, 2012

PARANEOPLASTIC DISORDERS Glucagonoma syndrome (necrolytic migratory erythema) – periorbital and perioral erythema; alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; skin rash, angular stomatitis, cheilosis, beefy red glossitis, blepharitis, conjunctivitis, alopecia, crumbling nails; rarely, associated with MEN I or IIA syndromes JAMA Derm 155:1180, 2019;; BJD 174:1092–1095, 2016; JAMA Derm 345–347, 2016; Int J Dermatol 49:24–29, 2010; JAAD 54:745–762, 2006; J Eur Acad Dermatol 18:591–595, 2004; JAAD 12:1032–1039, 1985; Int J Derm 43:12–18, 2004; AD 133:909, 912, 1997; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979; AD 45:1069–1080, 1942 Glucagon cell adenomatosis – necrolytic migratory erythema; cheilitis and painful glossitis JAAD 65:458–459, 2011

PHOTODERMATITIS Euphorbia trigona – phytophotodermatitis SKINmed 12:253–255, 2014

Erythrose peribuccale pigmentaire of Brocq – diffuse brown pigmentation around mouth with narrow perioral sparing; central face, forehead, angles of jaw, temples Facial Afro-Caribbean childhood eruption (FACE) – resembles perioral dermatitis Clin Exp Dermatol 15:163–166, 1990; BJD 91:435–438, 1976 Fine scaling, keratosis pilaris, periorificial crusting, palmoplantar hyperkeratosis, blistering JAAD 34:379–385, 1996 Granulomatous periorificial dermatitis AD 142:775–780, 2006; extrafacial and generalized periorificial dermatitis AD 138:1354– 1358, 2002 Intertrigo Lichen planus, hypertrophic – personal observation Lichen sclerosus et atrophicus – peristomal around ureterostomies BJD 168:643–646, 2013 Lichen simplex chronicus Lip licker’s dermatitis Can Fam Physician 48:1051, 1059, 2002; Napkin psoriasis – personal observation Perianal pseudoverrucous papules and nodules in children – perianal hypertrophic plaques; due to leakage of stool and/or urine Cutis 67:335–338, 2001; J Pediatr 125:914–916, 1994; AD Perioral dermatitis Stat Pearl Nov 17, 2019; Int J Derm 42:514–517, 2003 Periorbital dermatitis (periorbital variant of perioral dermatitis) – idiopathic or topical corticosteroid-associated Rook p. 2110–2111,3551, 1998, Sixth Edition Peristomal papillomatous dermatitis – conduit urinary diversion JAAD 19:623–628, 1988; Scand J Urol Nephrol 13:201–204, 1979 Psoriasis Cutis 43:157–158, 1989; peristomal irritant contact dermatitis – annular scaling dermatitis BJD 166:103–109, 2012 Peristomal pseudoverrucous papules – umbilicated papules Ped Derm 36:713–715, 2019 Psoriasis surrounding enteral feeding tube Ped Derm 31:68–72, 2014 Rosacea – lupus miliaris disseminate faciei Dermatol Ther 19:196–201, 2006 Seborrheic dermatitis Trichodysplasia spinulosa (viral-associated trichodysplasia spinulosa) – acneiform; follicular crusted papules with keratotic spines; lesions of face, neck with eyebrow alopecia; trichodysplasia spinulosa-associated polyoma virus AD 148:863–864, 2012; AD 147:1215–1220, 2011; perioral papules with white spicules – in nevoid basal cell carcinoma syndrome treated with vismodegib JAMA Derm 150:1016–1018, 2014 Vitiligo

PRIMARY CUTANEOUS DISEASE Acanthosis nigricans Atopic dermatitis – personal observation Childhood granulomatous perioral dermatitis J Eur Acad DV 19:470–473, 2005; Cutis 73:399–402, 2004; AD 138:1354–1358, 2002; Ped Derm 13:131–134, 1996; AD 128:1703–1708, 1989 Epidermolysis bullosa, junctional – letalis (atrophicans generalisata gravis, Herlitz type) – extensive blistering and erosions at birth; perioral and nasal exuberant granulation tissue and erosions Epidermolysis Bullosa: Basic and Clinical Aspects. NewYork: Springer, 1992: 118–134; JAAD 12:836–844, 1985; also junctional EB mitis; cicatricial junctional epidermolysis bullosa

PSYCHOCUTANEOUS DISEASES Factitial dermatitis – peristomal ulcers AD 142:1372–1373, 2006

SYNDROMES Acantholytic ectodermal dysplasia (similar to McGrath syndrome) – curly hair, palmoplantar keratoderma, skin fragility, hyperkeratotic fissured plaques with perioral involvement, red fissured lips, nail dystrophy BJD 160:868–874, 2009

Dermatographism Anhidrotic ectodermal dysplasia – hyperpigmentation around mouth and eyes; mutation in ectodysplasin A1 isoform (EDA-1) receptor (ADAR) BJD 157:207–209, 2007

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Basaloid follicular hamartoma syndrome – autosomal dominant; milia, comedone-like lesions, dermatosis papulosa nigra, skin tag-like lesions, hypotrichosis, multiple skin-colored, red, and hyperpigmented papules of the face in periorificial distribution, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes); hypohidrosis Cutis 78:42–46, 2006; JAAD 49:698–705, 2003; BJD 146:1068– 1070, 2002; JAAD 45:644–645, 2001; JAAD 43:189–206, 2000; JAAD 27:237–240, 1992

Olmsted syndrome – periorificial keratotic plaques; congenital diffuse sharply marginated transgradient keratoderma of palms and soles, onychodystrophy, constriction of digits, diffuse alopecia, thin nails, chronic paronychia, leukokeratosis of oral mucosa, linear keratotic streaks, follicular keratosis, constriction of digits (ainhum), anhidrosis, small stature; differential diagnostic considerations include Clouston hidrotic ectodermal dysplasia, pachyonychia congenita, acrodermatitis enteropathica, Vohwinkel’s keratoderma, mal de Meleda, and other palmoplantar keratodermas JAMA Derm 156:196–200, 2020; Ped Derm 36:942–943, 2019; JAAD 53:S266– 272, 2005; Ped Derm 21:603–605, 2004; Ped Derm 20:323–326, 2003; BJD 136:935–938, 1997; AD 132:797–800, 1996; JAAD 10:600–610, 1984; Am J Dis Child 33:757–764, 1927

Cystic fibrosis – autosomal recessive; dermatitis due to dietary deficiencies associated with the patient’s pancreatic dysfunction acrodermatitis enteropathica-like changes AD 128:1358–1364, 1992; JAAD 25:896–897, 1991; AD 119:l51–155, 1983; at initial presentation of cystic fibrosis AD 128:1358, 1992

Pseudoglucagonoma syndrome – periorificial erythema, crusted migratory plaques, hair loss, brittle nails, poor weight gain, onycholysis; associated with cirrhosis, celiac disease inflammatory bowel disease, small cell lung cancers Am J Med 126:387–389, 2013; Int J Derm 49:24–29, 2010

Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; mutation in PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 166:36–45, 2012; Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999

Sensorineural hearing loss, periorificial erythrokeratoderma, dental enamel defects, excess granulation tissue JID 121:1221–1223, 2003

Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC syndrome) – perioral and labial vegetative papillomatous plaques; perleche; high forehead, maxillary hypoplasia, mandibular protrusion Ped Derm 27:658–660, 2010; J Eur Acad DV 17:356–358, 2003; Ped Derm 19:330–332, 2002 Goltz's syndrome – perioral papules Clin Exp Dermatol 30:35–37, 2005; Cutis 53:309–312, 1994 Hereditary mucoepithelial dysplasia (dyskeratosis) (Gap junction disease, Witkop disease) – red eyes, non-scarring alopecia, keratosis pilaris, erythema of oral (palate, gingiva) and nasal mucous membranes, cervix, vagina, and urethra; perineal and perigenital psoriasiform dermatitis; increased risk of infections, fibrocystic lung disease BJD 153:310–318, 2005; Ped Derm 11:133–138, 1994; JAAD 21:351–357, 1989; Am J Hum Genet 31:414–427, 1979; Oral Surg Oral Med Oral Pathol 46:645–657, 1978

Shwachman syndrome – autosomal recessive; exocrine pancreatic insufficiency and bone marrow hypoplasia with neutropenia; cutaneous signs include generalized erythematous scaling eruptions, recurrent skin infections, generalized xerosis, red hands, and follicular keratoses of the trunk Ped Derm 9:57–61, 1992   Wiskott-Aldrich syndrome

TOXINS Thallium – anagen effluvium JAAD 50:258–261, 2004; nausea, vomiting, stomatitis, painful glossitis, diarrhea; severe dysesthesias and paresthesias in distal extremities, facial rashes of cheeks and perioral region, acneiform eruptions of face, hyperkeratosis of palms and soles, hair loss, Mees’ lines AD 143:93–98, 2007

TRAUMA Lip licking dermatitis with post-inflammatory hyperpigmentation

VASCULAR LESIONS Angiokeratoma corporis diffusum (Fabry’s disease (alpha galactosidase A) – X-linked recessive; initially, telangiectatic macules; perioral telangiectasias NEJM 276:1163–1167, 1967

Hereditary perioral pigmented follicular atrophoderma associated with milia and epidermoid cysts BJD 139:713–718, 1998

DERMATOGRAPHISM

KID syndrome – keratosis, ichthyosis, deafness syndrome – fixed orange, symmetrical hyperkeratotic plaques of scalp, ears, and face with perioral rugae; aged or leonine facies; erythrokeratoderma-like; later hyperkeratotic nodules develop Ped Derm 17:115–117, 2000; Ped Derm 13:105–113, 1996

JAAD 11:643, 1984

Mal de Meleda – autosomal dominant, autosomal recessive; transgrediens with acral erythema in glove-like distribution; perioral erythema and hyperkeratosis Dermatology 203:7–13, 2001; AD 136:1247–1252, 2000; J Dermatol 27:664–668, 2000; Dermatologica 171:30–37, 1985 Netherton’s syndrome Bull Soc Fr Dermatol Syphiligr 78:641–644, 1971

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Allergic contact dermatitis to poison ivy Allergic reactions to:  aspirin  sulfonamides  codeine   horse serum

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At site of previous allergic reaction Still’s disease, adult onset Mod Rheum 18:48—485, 2008;

Carvajal syndrome – autosomal recessive; woolly hair, striate palmoplantar keratoderma, dilated left ventricular cardiomyopathy

J Formos Med Assoc 103:844–852, 2004

Clubbing of nails Follicular hyperkeratosis of the elbows and knees

DRUGS

Lethal acantholytic epidermolysis bullosa BJD 166:36–45, 2012; Am J Hum Genet 77:653–660, 2005

Barbiturate and glutethimide poisoning

Leukonychia

Drug ingestion without drug eruption (penicillin)

Nail dystrophy

Famotidine (Pepcid) JAAD 31:671–678, 1994

Palmoplantar keratoderma – diffuse, striate, or linear Pustules of face, hands, hips at birth

INFECTIONS AND INFESTATIONS

Skin fragility-woolly hair syndrome JID 118:232–238, 2002 Oral erosions

Cheyletiella infestation

Tooth abnormalities – abnormal teeth, enamel defects

Helicobacter Rev Alerg Mex 49:99–102, 2002

Vesicular lesions of palms and soles

Hymenoptera stings – immediately following wasp and bee stings

Woolly hair – palmoplantar keratoderma, biventricular cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy

Scabies

Xerosis of palms and soles

INFILTRATIVE DISORDERS Mastocytosis – diffuse and systemic; urticaria pigmentosa Menopause, onset

INFLAMMATORY DISORDERS Eosinophilic synovitis Arthr Rheum 29:1147–1151, 1986

METABOLIC DISEASES

 IABETES MELLITUS, CUTANEOUS D MANIFESTATIONS SKINmed 9:302–308, 2011 Acanthosis nigricans Acquired perforating dermatosis associated with diabetes mellitus, chronic renal failure, hemodialysis Acrochordon (skin tags)

Diabetes mellitus

Anhidrosis – secondary acquired generalized anhidrosis BJD 150:589–593, 2004

Hypothyroidism and hyperthyroidism

Arteriosclerosis – peripheral vascular disease with leg ulcers

Intrahepatic cholestasis of infancy

Calcification of the auricle

Phenylketonuria Pregnancy (esp.last half)

Calluses – plantar calluses; painless hemorrhagic callus JAAD 70:1–18, 2014; neuropathic hemorrhagic calluses of feet

PRIMARY CUTANEOUS DISEASES

Carotenemia JAAD 57:1051–1058, 2007; Cutis 71:441–442, 448, 2003

Idiopathic – 4–5% of normal population

Charcot foot

Candida infection – paronychia, balanitis, angular cheilitis, intertrigo, anal pruritus, erosion interdigitalis blastomycetica

Dermatophytosis

SYNDROMES

Diabetic bulla (bullous diabeticorum) – intraepidermal or subepidermal separation without acantholysis JAAD 7:427–455, 1982

Hypereosinophilic syndrome Am J Hematol 78:33–36, 2005

Diabetic cheiropathy – sclerodermoid changes of hands; prayer sign BJD 171:1402–1408, 2014

Mast cell activation syndrome Am J Med Sci 353:207–215, 2017

TRAUMA Exercise Stress Tattoo sites

Diabetic finger pebbling (Huntley’s papules) Cutis 69:298–300, 2002 Diabetic dermopathy (annular atrophic patches of legs) (pretibial pigmented patches) JAAD 58:447–451, 2008; Am J Med Sci 251:570–575, 1966; AD 93:282–286, 1966; AD 92:625–634, 1965;Acta Med Scand 176 (Suppl) 1–75, 1964; pigmented hypertrichotic indurated plaques of thighs Ped Derm 24:101–107, 2007; linear atrophic brown scars Cutis 3:955–958, 1967 Diabetic lipohypertrophy – giant skin colored tumid mass BJD 171:1402–1406, 2014

DESMOPLAKIN MUTATIONS

Diabetic muscle infarction – swelling of thigh AD 143:1456–1457, 2007; Diabetalogica 1:39–42, 1965

Alopecia – diffuse, decreased body hair, eyelashes, eyebrows, shed hair

Diabetic rubor Dermatol Clin 7:531–546, 1989; Diabetes 14:201– 208, 1965

Cardiomyopathies – arrhythmogenic right ventricular cardiomyopathies

Dupuytren’s contracture Eruptive xanthomas

Diarrhea, Cutaneous Manifestations 269 Erysipelas-like erythema of legs or feet Acta Med Scand 196:333– 342, 1974

Leschke’s syndrome – growth retardation, mental retardation, diabetes mellitus, genital hypoplasia, hypothyroidism

Erythrasma, disciform

Lipodystrophy – insulin lipoatrophy, insulin lipohypertrophy

Gain of function STAT1 mutations – chronic mucocutaneous candidiasis; onychodystrophy, generalized dermatophytosis; disseminated coccidioidomycosis, histoplasmosis, sinopulmonary infections, herpes simplex infections; endocrine, dental, gastrointestinal disease; diabetes mellitus, hypothyroidism, autoimmune hepatitis, cerebral aneurysms, oral and esophageal squamous cell carcinomas; increased levels of interferon results in decreased IL-17A and IL-22 JAAD 73:255–264, 2015

Malignant external otitis infection

Glucagonoma syndrome Granuloma annulare, disseminated Grinspan’s syndrome – oral lichen planus, diabetes mellitus, hypertension

Mucormycosis, rhinocerebral Necrobiosis lipoidica diabeticorum BJD 171:1402–1406, 2014; ulcerated facial plaque AD 130:1433–1436, 1994; Acta DV 58:276–277, 1978; starts as red papule Int J Derm 33:605–617, 1994; JAAD 18:530–537, 1988; necrobiosis lipoidica diabeticorum Ped Derm 27:178–181, 2010; Int J Derm 33:605–617, 1994; JAAD 18:530–537, 1988; yellow nodules AD 143:546–548, 2007; ulcerative necrobiosis lipoidica diabeticorum JAMA Derm 149:879– 881, 2013; Ped Derm 27:178–181, 2010; AD 145:437–439, 2009; AD 142:20–22, 2006; JAAD 17:351–354, 1987 Necrotizing fasciitis

Group B streptococcal infections

Neuropathic ulcers (mal perforans)

H syndrome – autosomal recessive; facial telangiectasias; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, short stature, facial telangiectasia, gynecomastia, camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azoospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly; Arabic Palestinian population; gluteal lipoatrophy; hyperpigmentation, hearing loss, diabetes mellitus, lymphadenopathy, hypertrichosis, heart anomalies, micropenis, hallus valgus, hyperpigmentation induration and hypertrichosis of inner thighs and shins (sclerodermoid), chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 Ped Derm 32:731–732, 2015; JAAD 70;80– 88, 2014; JAAD 59:79–85, 2008

Palmar erythema Cutis 89:84–88, 2012; Cutis 89:84–88, 2012

Hemochromatosis JAMA 312:743–744, 2014 Meralgia paresthetica (Bernhard-Roth syndrome) (lateral femoral cutaneous nerve neuralgia) – pruritus or dysesthesia of lateral or antero-lateral upper thigh; association with diabetes JAAD 74:215– 228, 2016 Migratory ichthyosiform dermatosis (polycyclic ichthyosiform rash) with type 2 diabetes mellitus and insulin resistance AD 135:1237– 1242, 1999; Diabetes Care 21:1032, 1998 Insulin-resistant diabetes mellitus with acanthosis nigricans and hypertension – autosomal recessive; severe hyperinsulinemia, amenorrhea, hirsutism; mutation in muscle-specific regulatory subunit of protein phosphatase 1 (PPAR-gamma and PP1R3A) BJD 147:1096–1011, 2002 Migratory ichthyosiform dermatosis with type 2 diabetes mellitus and insulin resistance; polycyclic ichthyosiform rash AD 135:1237– 1242, 1999 IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash; mutations in FOXP3 gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia BJD 160:645–651, 2009; ichthyosiform eruptions Blood 109:383–385, 2007; NEJM 344:1758–1762, 2001; alopecia areata AD 140:466–472, 2004 Leg ulcers Diabet Med 16:889–909, 1999; Diabetes 40:1305–1313, 1991; necrobiosis lipoidica diabeticorum, ulcerative neuropathic and large vessel and microvascular foot ulcers (mal perforans);

Parotid gland enlargement Oral Surg Oral Med Oral Pathol 52:594–598, 1981; JAMA 232:20, 1975 Pemphigus vulgaris – association with autoimmune thyroid disease, rheumatoid arthritis, type 1 diabetes mellitus BJD 172:729–738, 2015 Perforating folliculitis – keratotic papules JAAD 63:179–182, 2010; Am J Dermatopathol 20:147–154, 1998; AD 97:394–399, 1968; Kyrle’s disease BMJ Case Rep Nov1, 2017 Perineural xanthoma in diabetes mellitus – tender red nodule of back Cutis 92:299–302, 2013 Peripheral neuropathy – livedo reticularis JAAD 52:1009–1019, 2005 Primrose syndrome – enlarge calcified ears; distal muscle wasting, diabetes, deafness, basal ganglia calcification Mol Syndromol 9:70–82, 2018 Polyglandular autoimmune syndrome Post-inflammatory hyperpigmentation – lentigo-like macules BJD 171:1402–1406, 2014 Premature aging syndrome with osteosarcoma, cataracts, diabetes mellitus, osteoporosis, erythroid macrocytosis, severe growth and developmental deficiency Am J Med Genet 69:169– 170, 1997 Reactive perforating collagenosis Scleredema diabeticorum Staphylococcus aureus infections Vitiligo Woodhouse-Sakati syndrome – autosomal recessive; triangular shaped face with prominent forehead, large low set ears, dystonia, hypotrichosis, with sparse eyebrows and eyelashes; alopecia, hypogonadism, diabetes mellitus, mental retardation, sensorineural deafness, extrapyramidal signs, low insulin-like growth factor 1; must be differentiated from congenital hypotrichosis; mutation in C2orf37 Ped Derm 31:83–87, 2014; Am J Med Genet 143:149–160, 2007; J Med Genet 20:216–219, 1983 Xerosis Skin Res Technol 8:250–254, 2002

DIARRHEA, CUTANEOUS MANIFESTATIONS NEJM 365:2306–2316, 2011

270 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

IMMUNE DYSREGULATION Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – loss of function mutation in cat eye syndrome chromosome candidate 1 gene (CECR1); painless leg nodules with intermittent livedo reticularis, Raynaud’s phenomenon, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae; vasculitis of small and medium arteries with necrosis, fever, early recurrent ischemic and hemorrhagic strokes, peripheral and cranial neuropathy, and gastrointestinal involvement (diarrhea); hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:199–201, 2020; NEJM 380:1582–1584, 2019; Ped Derm 33:602–614, 2016; NEJM 370:911–920, 2014; NEJM 370:921–931, 2014

INFECTIONS NEJM 370:1532–1540, 2014 BACTERIAL Bacterial overgrowth of small intestine – malabsorption syndrome Bacteroides Campylobacter jejuni – chronic bloody or inflammatory diarrhea NEJM 370:1524–1531, 2014 Clostridium difficile – bloody or inflammatory diarrhea DOCK2 deficiency – early onset invasive bacterial and viral infections NEJM 372:2409–2422, 2015 Epidemic typhus (Rickettsia prowazekii) – morbilliform eruption becomes petechial exanthema; fever, nausea, diarrhea, delirium, respiratory failure, shock JAAD 82:551–569, 2020 Ehrlichia chaffeensis (human monocytic ehrlichiosis) – fever, headache, malaise, myalgia; nausea, vomiting, diarrhea, abdominal pain; 1/3 with petechial or morbilliform eruption or diffuse erythema MMWR 65:1–44, May 23, 2016; Clin Inf Dis 34:1206–1212, 2002; J Clin Gastroenterol 25:544–545, 1997 Escherichia coli with Shiga toxin production NEJM 370:1524–1531, 2014 Hyper IgM syndrome – recurrent pulmonary and diarrheal infections; mutation in gene encoding CD40 ligand

Yersiniosis (Yersinia enterocolitis) – erythema nodosum MCNA 61:639–653, 1982 FUNGAL All may be associated with simultaneous oral or nasopharyngeal ulcers; impede bile salt reabsorption Cryptococcosis – molluscum-like lesions BMJ Case Rep Dec14, 2012 Histoplasmosis – African histoplasmosis with molluscum-like lesions, HIV J Mycol Med Oct 16, 2019 Paracoccidioides brasiliensis (South American blastomycosis) PROTOZOAL OR PARASITE Amebic ulcers (Entamoeba histolytica) – ulcers of vulva and perineum; often accompanied by diarrhea; serpiginous ulcer Cutis 90:310–314, 2012; JAAD 60:897–925, 2009; AD 144:1369–1372, 2008; Ped Derm 23:231–234, 2006; Ped Derm 10:352–355, 1993; Pediatrics 71:595–598, 1983; Arch Dis Child 55:234–236, 1980; Mod Probl Paediatr 17:259–261, 1975; Am J Proctol 17:58–63, 1966; Dientamoeba fragilis Cryptosporidium hominis; C parvum – prolonged, severe, and potentially life-threatening diarrhea in cellularly immunocompromised host Gnathostomiasis – intermittent migratory swellings and nodules; subcutaneous hemorrhages along tracks of migration; urticarial, abdominal pain, nausea and vomiting, diarrhea; South East Asia JAAD 73:929–944, 2015 Leishmania species – in severe cellularly immunocompromised host Microsporidial (Enterocytozoon bieneusi and Encephalitozoon intestinalis) – in severely immunocompromised host VIRAL INFECTIONS Cytomegalovirus infection – perianal punched out ulcers; bloody diarrhea DOCK2 deficiency – early onset invasive bacterial and viral infections NEJM 372:2409–2422, 2015

Mycobacterium tuberculosis – impede bile salt reabsorption

Ebola virus hemorrhagic fever (Filovirus) – morbilliform exanthem which becomes purpuric with desquamation of palms and soles; high fever, body aches, myalgia, arthralgias, prostration, abdominal pain, watery diarrhea; disseminated intravascular coagulation Int J Dermatol 51:1037–1043, 2012; JAMA 287:2391–2002; Int J Dermatol 51:1037–1043, 2012; JAAD 65:1213–1218, 2011; MMWR 44, No.19, 382, 1995

Rocky Mountain spotted fever MMWR 65:1–44, May 13, 2016

Enteric adenoviruses

Salmonellosis – nontyphoidal salmonellosis; enteric fever, bacteremic salmonellosis, including typhoid fever; chronic carriage of typhoidal salmonella NEJM 370:1524–1531, 2014

Herpes simplex virus – proctitis or colitis; cellularly immunocompromised

Lymphogranuloma venereum – diarrhea and proctitis Clin Inf Dis 67:1775–1776, 2018 Meningococcemia – first symptom is often diarrhea Mycobacterium avium – impede bile salt reabsorption

Shigellosis NEJM 370:1524–1531, 2014 Traveler’s diarrhea and enterotoxigenic E. coli NEJM 370:1524– 1531, 2014 Tularemia – ingesting raw grapes; diarrhea cervical adenopathy, fever, difficulty swallowing NEJM 379:197–198, 2018 Vibrio cholera infection (cholera) NEJM 370:1524–1531, 2014; noncholeraic vibrio diarrhea Whipple’s disease (Tropheryma whipplie) – non-palpable purpura, chronic leg edema, arthralgias; large dilated abdominal lymphatics; diarrhea, weight loss, abdominal pain, generalized hyperpigmentation, pulmonary hypertension, eye, cardiovascular, and neurologic disease Clin Infect Dis 41:519–520,557–559, 2005; arthritis, rash, diarrhea, neurologic symptoms

HHV-6 reactivation in chronic graft vs. host disease – morbilliform eruption, fever, diarrhea JAAD 72:696–702, 2015 HIV enteropathy – acute HIV-1 infection NEJM 16:313, 2009 Lassa fever – capillary leak syndrome with severe swelling of head and neck, oral ulcers, tonsillar patches JAAD 65:1213–1218, 2011 Lipschutz ulcer (ulcus vulvae acutum) (genital ulcers in teenagers) – acute genital (vulvar) ulcer accompanying tonsillitis and fever with flu-like symptoms; Epstein-Barr virus in 1/3 of patients Cutis 91:273–276, 2013; JAAD 63:44–51, 2010; AD 145:38–45, 2009; Ped Derm 25:113–115, 2008; Eur J Dermatol 13:297–298, 2003; J Pediatr 11:185, 1998; Obstet Gynecol 92:642, 1998; Sex Transm Infec 74:296–297, 1998; BJD 135:663–665, 1996; Genitourin Med 70:356, 1994; Acta DV 45:221–222, 1965; Archives of Dermatology Syphilol 20:363–396, 1912; associated with upper respiratory

Diarrhea, Cutaneous Manifestations 271 infections, viral gastroenteritis, Epstein-Barr virus, cytomegalovirus, Mycoplasma, influenza A, streptococcal pharyngitis, mumps JAAD 68:885–896, 2013

Dimethylfumarate – treatment for multiple sclerosis J Drugs in Dermatol 13:1144–1147, 2014

Measles – diarrhea, headache, chills, myalgias, nausea and vomiting, red eyes, exanthema, enanthem, fever and rash Clin Inf Dis 62:1021,1049, 2016; NEJM 372:2217, 2015; NEJM 372:2218– 2223, 2015

Griseofulvin

PARASITIC INFECTIONS Cysticercosis (Taenia solium) (Cysticercus cellulosae) – undercooked pork; multiple asymptomatic subcutaneous nodules; multiple red painless nodules of legs; abdominal pain, muscle edema and pain; diarrhea; neurocysticercosis JAAD 73:929–944, 2015; JAAD 43:538–540, 2000; JAAD 25:409–414, 1991; NEJM 330:1887, 1994; JAAD 12:304–307, 1985 Fascioliasis (Fasciola hepatica, F. gigantica) – liver fluke; urticaria, jaundice, diarrhea, serpiginous tracts, subcutaneous nodules JAAD 73:929–944, 2015; BJD 145:487–489, 2001

DRESS syndrome Ibrutinib – diarrhea, brittle fingernails and toenails with onychorrhexis JAMA Derm 152:698–701, 2016 Toxic shock syndrome EXOGENOUS AGENTS Laxative abuse Marijuana – hyperemesis syndrome – periods of nausea, vomiting, abdominal pain; compulsive bathing Clin Inf Dis 61:1840–1849, 2015 Senneca laxative – blistering erosive diaper dermatitis; diamondshaped erosion of buttocks with linear borders aligning with diaper edge; spares perianal area and gluteal cleft AD 148:402–404, 2012; Pediatrics 107:178–179, 2001

Schistosomiasis (S. japonicum) – Katayama fever (acute schistosomiasis) – red papular exanthem, fever, cough, urticarial eruption, fatigue, pulmonary nodules; purpura, arthralgia, systemic symptoms; diarrhea, edema, headache, arthralgias, abdominal pain, hypereosinophilia occurring 4–6 weeks after infection NEJM 374:469, 2016; JAAD 73:929–944, 2015; BJD 135:110–112, 1996; Dermatol Clin 7:291–300, 1989

Shiitake mushroom dermatitis – raw mushrooms, linear flagellate dermatitis, pruritus, fever, diarrhea, mucosal ulcers Int J Dermatol 56:610–616, 2017

Strongyloidiasis – Strongyloides stercoralis; hyperinfection syndrome – parasitic periumbilical thumbprint purpura NEJM 370:1524–1531, 2014; urticaria, larva currens J Ped Child Health 55:364–366, 2019

Infantile systemic hyalinosis – autosomal recessive; red pearly facial papules, synophrys, thickened skin, perianal nodules, dusky red plaques of buttocks, gingival hypertrophy, joint contractures, juxta-articular nodules (knuckle pads), osteopenia, growth failure, diarrhea, frequent infections; mutation in CMG 2 (capillary morphogenesis protein 2) JAAD 58:303–307, 2008; JAAD 50:S61–64, 2004; Pediatr Pathol 6:55–79, 1986

Trichinosis – initially have abdominal pain and diarrhea; periorbital facial edema, subconjunctival hemorrhage, splinter hemorrhages, macular or petechial rash Clin Inf Dis 59:1750–1756, 2014; Parasite 13:63–70, 2006

NON-INFECTIOUS AUTOIMMUNE DISEASES Dermatitis herpetiformis – gluten sensitive enteropathy Graft vs host disease Am J Dermatopathol 40:754–757, 2018 Gain of function mutation of NLRC4 (inflammasome) – fever, periodic urticarial rash, conjunctivitis, arthralgias, painful red nodules of foot or leg, enterocolitis, splenomegaly, macrophage activation syndrome; increased IL-18 BJD 176:244–248, 2017; Nat Genet 46:1135–1139, 2014; Nat Genet 46:1140–1146, 2014; J Exp Med 211:2385–2396, 2014Scleroderma BMJ Case Rep Sept 28, 2018

INFILTRATIVE DISORDERS Primary cutaneous amyloidosis

Mastocytosis – small pink patches, with flushing and diarrhea Am J Hematol 88:612–624, 2013; Am J Clin Dermatol 12:259–270, 2011; NEJM 363:72–78, 2010 INFLAMMATORY DISORDERS Ankylosing spondylitis – associated findings include psoriasis, anterior uveitis, inflammatory bowel disease, lung abnormalities, heart conduction defects, aortic insufficiency, renal abnormalities, osteoporosis, vertebral fractures Euro J Intern Med 2011:1–7; Int J Rheumatol 2011:1–10 Inflammatory bowel disease – ulcerative colitis, Crohn’s disease, pyoderma gangrenosum; sterile pustules; erythema nodosum; oral aphthae Crohn’s disease – knife cut perineal ulcerations Pan Afr Med J 33:231, 2019

X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with unswept hair, flared eyebrows; female carriers display blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

Microscopic colitis

DRUGS

METABOLIC DISORDERS

Adalimumab – ulcerative colitis BJD 178:551–555, 2018

Acrodermatitis enteropathica (zinc deficiency) – periorificial dermatitis, generalized dermatitis, vesicular, bullous, pustular, desquamative dermatitis, psoriasiform dermatitis, alopecia, paronychia, perleche Cutis 81:314, 324–326, 2008; JAAD 56:116– 124, 2008; Ped Derm 19:426–431, 2002; angular cheilitis Cutis 82:60–62, 2008; Ped Derm 19:426–431, 2002; Acta DV 17:513–

Azathioprine hypersensitivity syndrome – fever, chills, erythema nodosum, Sweet’s syndrome, leukocytoclastic vasculitis, pustular drug eruption, urticarial, purpuric eruption, leukocytosis, nausea, vomiting, diarrhea JAAD 65:184–191, 2011 Colchicine – Behcet’s disease Turk Ped Ass 54:179–184, 2019

Pyostomatitis vegetans – sign of ulcerative colitis Acta DV 81:134–136, 2001; JAAD 31:336–341, 1994 Ulcerative colitis – sterile abscesses JAAD 42:363–365, 2000; peristomal ulcers AD 142:1372–1373, 2006

272 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 546, 1936; acquired zinc deficiency with erythema and scaling of entire vermilion Aphthae – Crohn’s disease, Behcet’s disease, HIV disease, ulcerative colitis Celiac disease – oral aphthae, paronychia Dumping syndrome – flushing, abdominal pain, diarrhea JAAD 55:193–208, 2006 Essential fatty acid deficiency – xerosis, scaly diffuse erythema, intertriginous erosions, capillary fragility, alopecia, brittle nails, poor wound healing Fabry’s disease Hartnup disease – niacin deficiency (pellagrous dermatitis) Hyperthyroidism – urticaria Kwashiorkor – protein malnutrition Lactase deficiency Malabsorption – angular cheilitis; xerosis Marasmus – protein and calorie malnutrition Motility disorders Necrolytic migratory erythema – serpiginous, annular papulosquamous eruptions; glucagonoma, chronic liver disease, inflammatory bowel disease, heroin abuse, pancreatitis, malabsorption syndromes; periorbital and perioral erythema; alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; skin rash, angular stomatitis, cheilosis, beefy red glossitis, blepharitis, conjunctivitis, alopecia, diarrhea, crumbling nails; rarely, associated with MEN I or IIA syndromes BJD 174:1092–1095, 2016; JAMA Derm 345–347, 2016; JAAD 54:745–762, 2006; JAAD 12:1032–1039, 1985; Int J Derm 43:12–18, 2004; AD 133:909, 912, 1997; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979; AD 45:1069–1080, 1942

PARANEOPLASTIC SYNDROME Dermatomyositis South Med J 90:321–324, 1997 Glucagonoma syndrome – alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; recurrent seborrheic, serpiginous, annular papulosquamous eruptions; angular stomatitis, cheilosis, beefy red atrophic glossitis, blepharitis, conjunctivitis, alopecia, crumbling nails; rarely, associated with MEN I or IIA syndromes JAAD 68:189–209, 2013; AD 143:1221–1222, 2007; AD 133:909, 912, 1997; JAAD 24:473–477, 1991; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979 Medullary carcinoma of the thyroid – MEN IIA, IIB – facial flushing, diarrhea, hoarseness, bone pain JAAD 77:391–402, 2017; Clin Med Res 16:16–28, 2018 Neuroendocrine tumor – facial flushing, abdominal pain, diarrhea; hepatic metastases; elevated chromogranin and 5-hydroxyindoleacetic acid levels; tricuspid regurgitation NEJM 371:260, 2014 Pheochromocytoma – episodic sweating, headache, tachycardia, flushing, pallor, Raynaud’s Clin Med Res 16:16–28, 2018 POEMS syndrome – flushing, hyperpigmentation, hypertrichosis, acrocyanosis Clin Med Res 16:16–28, 2018 Vasoactive intestinal peptide-secreting tumors – watery diarrhea (Verner-Morrison syndrome) JAAD 77:391–402, 2017 Zollinger-Ellison syndrome NEJM 368;757–765, 2014 PRIMARY CUTANEOUS DISEASES Acquired ichthyosis – malabsorption Infantile perineal protrusion – differential diagnosis includes hemorrhoids, rectal prolapse, skin tags, sexual abuse, sentinel tag of anal fissure, inflammatory bowel disease, perineal midline malformation, hemangioma JAAD 54:1046–1049, 2006

Pancreatic insufficiency

Jacquet’s erosive diaper dermatitis

Pellagra (niacin deficiency) – angular stomatitis; crusted lips; Casal’s necklace; red pigmented sharply marginated photodistributed rash, including drug-induced pellagra-like dermatitis – 6-mercaptopurine, 5-fluorouracil,INH (all of the above – also seborrheic dermatitis-like); resembles Hartnup disease; carcinoid syndrome NEJM 371:2218– 2223, 2014; BJD 164:1188–1200, 2011; Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; BJD 125:71–72, 1991; vulvitis

Leiner’s disease – seborrheic dermatitis, erythroderma Clin Exp Dermatol 14:364–366, 1989; Dermatol Therapy 18:176–183, 2005

Porphyria – variegate porphyria; acute intermittent porphyria – abdominal scars Serotonin syndrome – tremor, diarrhea, tachycardia, shivering, diaphoresis, mydriasis, nystagmus, hypertonicity, clonus, hyperreflexia, hypertension, hyperthermia, agitation, increased bowel sounds, spasms, salivation, flushing, delirium, rigidity, coma, metabolic acidosis, disseminated intravascular coagulation JAAD 77:391–402, 2017 Short bowel syndrome Tropical sprue – malabsorption syndrome Wilson’s disease – diarrhea, nausea, and weight loss NEJM 371:1238–1247, 2014 NEOPLASTIC DISORDERS Kaposi’s sarcoma Gastrointest Tumor 6:51–55, 2019; J Invest Med High Impact Case Rep June 12, 2017 Lymphoma Villous adenoma – familial adenomatous polyposis Orphanet I Rare Dis Oct 12, 2009

SYNDROMES APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy) syndrome (autoimmune polyendocrine syndrome type 1) – autosomal recessive; mutation in AIRE gene (autoimmune regulator gene); chronic mucocutaneous candidiasis, hypoparathyroidism, Addison’s disease, diabetes mellitus type 1, thyroid autoimmune disease, gonadal failure, hepatitis, vitiligo, alopecia areata, pernicious anemia, intestinal malabsorption, keratopathy, dystrophy of dental enamel and nails JAAD 62:864–868, 2010 APLAID (autoinflammation and PLAID) – sinopulmonary infections, interstitial pneumonitis, eye inflammation, colitis, arthralgias; epidermolysis bullosa-like eruptions in infancy with vesiculopustular lesions and red plaques JAAD 73:367–381, 2015 APLAID (autoinflammation and PLAID) –sinopulmonary infection, interstitial pneumonitis, eye inflammation, colitis, arthralgias; epidermolysis bullosa-like eruptions in infancy with vesiculopustular lesions and red plaques JAAD 73:367–381, 2015 Ballard-Gerold syndrome – poikiloderma, craniosynostosis, radial ray defects, patellar and palatal abnormalities, dislocated joints, diarrhea, short stature, slender nose, normal intellect; RECQL4 mutations JAAD 75:855–870, 2016; Soc Ped Dermatol Annual Meeting, 2006 Behcet’s disease – arthritis, oral aphthae, acneiform eruptions BJD 159:555–560, 2008; JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999; JAAD 36:689–696, 1997; Ped Derm 11:95–101, 1994

Diarrhea, Cutaneous Manifestations 273 Biotinidase deficiency (biotin deficiency) (multiple carboxylase deficiencies) – psoriasiform, periorificial intertriginous dermatitis; diarrhea, alopecia Ped Derm 33:457–458, 2016; NEJM 304:820– 823, 1981 Brainerd’s diarrhea – epidemic chronic diarrhea Carcinoid syndrome – pellagrous dermatitis (skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea JAMA Derm 153:925–926, 2017; BJD 152:71–75, 2005; AD 77:86–90, 1958 Cronkhite-Canada syndrome – lentigo-like macules of face, extremities, and diffuse pigmentation of palms; hyper- and hypopigmented macules of dorsal fingers; gastrointestinal polyposis, malabsorption, alopecia, dystrophic nails; IgG4 infiltration of colonic polyps JAAD 63:172–174, 2010; AD 135:212, 1999; Cutis 61:229– 232, 1998 Fanconi syndrome, ichthyosis, dysmorphism, jaundice, and diarrhea Pediatr Nephrol 4:308–313, 1990 Hereditary angioneurotic edema (Quincke’s edema) Hermansky-Pudlak syndrome – oculocutaneous albinism, hemorrhage, ceroid-like material deposited in several organs; granulomatous colitis, pulmonary fibrosis, renal failure, cardiomyopathy, hypothyroidism Ped Derm 34:638–646, 2017; SKINmed 12:313– 315, 2014 Hypereosinophilic syndrome – intractable pruritus, pulmonary infiltrates, eosinophilic gastroenteritis, endomyocardial fibrosis, thromboembolism NEJM 380:1336–1346, 2019AD 132:535–541, 1996; Med Clin (Barc) 106:304–306, 1996 Hyper IgD syndrome – autosomal recessive; morbilliform eruptions, red macules or papules, urticaria, red nodules, urticaria, combinations of recurrent periodic fever, no arthritis, rather arthralgias, and rash, annular erythema, and pustules, abdominal pain with vomiting and diarrhea, oral and vaginal aphthae; splenomegaly, cervical lymphadenopathy; elevated IgD and IgA – mevalonate kinase deficiency (MVK); seen in Dutch JAAD 68:834–853, 2013; AD 144:392–402, 2008; Ped Derm 22:138–141, 2005; AD 136:1487– 1494, 2000; AD 130:59–65, 1994; Medicine 73:133–144, 1994; Lancet 1:1084–1090, 1984 IPEX syndrome – X-linked; immune dysregulation, polyendocrinopathy (diabetes mellitus, thyroiditis), autoimmune enteropathy (neonatal diarrhea); mutation of FOXP3 gene encodes DNA-binding protein that suppresses transcription of multiple genes involved in cytokine production and T cell proliferation; (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; or nummular dermatitis, ichthyosiform dermatitis, painful fissured cheilitis, edema of lips and perioral area, urticaria, scaly psoriasiform plaques of trunk and extremities, onychodystrophy, penile rash, alopecia universalis, trachyonychia, bullae; pemphigoid nodularis (bullae and prurigo nodularis), membranous glomerulonephritis, autoimmune thyroid disease, hepatitis, nephritis, exocrine pancreatitis; mutations in FOXP3 (forkhead box protein 3) gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia NEJM 378:1132–1141, 2018; JAAD 73:355–364, 2015; BJD 160:645–651, 2009; JAAD 55:143–148, 2006; AD 140:466–472, 2004; J Pediatr 100:731–737, 1982; ichthyosiform eruptions Blood 109:383–385, 2007; BJD 152:409–417, 2005; NEJM 344:1758– 1762, 2001; alopecia areata AD 140:466–472, 2004 X-rash urticaria secondary to foods); Irritable bowel syndrome Kawasaki’s disease POEMS syndrome (Crow-Fukase syndrome, Takatsuki syndrome) (PEP syndrome – plasma cell dyscrasia, endocrinopathy, polyneu-

ropathy) – plethora, angiomas (cherry, globular, glomeruloid) presenting as red nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, scleroderma-like changes, either generalized or localized (legs), hyperhidrosis, clubbing, leukonychia, papilledema, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss, fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias; osteosclerotic myeloma (IgG or IgA lambda) bone lesions, progressive symmetric sensorimotor peripheral polyneuropathy, hypothyroidism, and hypogonadism; peripheral edema, thrombocytosis, cutaneous angiomas, blue dermal papules associated with Castleman’s disease (benign reactive angioendotheliomatosis), maculopapular brown-violaceous lesions, purple nodules; papilledema JAAD 58:671–675, 2008; JAAD 55:149–152, 2006; JAAD 44:324–329, 2001, JAAD 40:808–812, 1999; AD 124:695–698, 1988, Cutis 61:329–334, 1998; JAAD 21:1061–1068, 1989; JAAD 12:961–964, 1985; Nippon Shinson 26:2444–2456, 1968 Mental retardation-enteropathy-deafness-neuropathy-ichthyosis-­­ keratodermia syndrome JAAD 63:607–641, 2010; Proc Natl Acad Sci USA 4:1–9, 2009 NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic self-limiting fever, polyarthritis, polyarthralgia, red plaques of face and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013 Omenn syndrome (familial reticuloendotheliosis with eosinophilia) – autosomal recessive; neonatal exfoliative erythroderma, subacute combined immunodeficiency, diarrhea, hepatosplenomegaly, alopecia of scalp and eyebrows, failure to thrive, lymphadenopathy Clin Exp Dermatol 45:646–649, 2020; BJD 158:1153–1156, 2008; AD 136:875–880, 2000; Ped Derm 17:91–96, 2000; Ped Derm 14:49–52, 1997; JAAD 25:442–446, 1991 Powell syndrome – X-linked, intractable diarrhea, autoimmune polyendocrinopathy, dermatitis, hemolytic anemia Am J Med Genet 66:378–398, 1996 Pseudoglucagonoma syndrome – periorificial erythema, crusted migratory plaques, hair loss, brittle nails, diarrhea, poor weight gain, onycholysis; associated with cirrhosis, celiac disease inflammatory bowel disease, small cell lung cancers Am J Med 126:387–389, 2013 RAPADILINO syndrome – radial ray defects, limb malformations, diarrhea in infancy, short stature; osteosarcoma RECQL4 mutations AD 141:617–620, 2005 Reactive arthritis – keratoderma blenorrhagicum; flexural confluent circinate lesions Rook p. 2765–2766, 1998; Semin Arthritis Rheum 3:253–286, 1974; circinate balanitis; nail changes indistinguishable from psoriasis Rothmund-Thomson syndrome – diarrhea and vomiting JAAD 75:855–870, 2016 Schwachman’s syndrome – neutropenia, malabsorption, failure to thrive; generalized xerosis, follicular hyperkeratosis, widespread dermatitis, palmoplantar hyperkeratosis Ped Derm 9:57–61, 1992; Arch Dis Child 55:531–547, 1980; J Pediatr 65:645–663, 1964 Verner-Morrison syndrome (watery diarrhea syndrome) – flushing; pancreatic cholera X-linked reticulate pigmentary disorder with systemic manifestations (familial cutaneous amyloidosis) (Partington syndrome II) – X-linked; rare; Xp21–22; boys with generalized reticulated muddy brown reticulated pigmentation (dyschromatosis) with hypopigmented corneal dystrophy (dyskeratosis), coarse unruly hair, unswept eyebrows, silvery hair, hypohidrosis, recurrent sinus disease and pneumonia with chronic obstructive disease, clubbing; photophobia, failure to thrive, female carriers with linear macular nevoid Blaschkoesque hyperpigmentation; gastroenteritis, diarrhea; intronic mutation

274

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

of POLA1 gene JAMA Derm 153:817–818, 2017; Ped Derm 32:871–872, 2015; Am J Med Genet 161:1414–1420, 2013; Eur J Dermatol 18:102–103, 2008; Ped Derm 22:122–126, 2005; Semin Cut Med Surg 16:72–80, 1997; Am J Med Genet 32:115–119, 1989; Am J Med Gen 10:65–75:1981   Differential diagnosis includes:   Dermatopathia pigmentosa reticularis – adermatoglyphia, palmoplantar keratoderma, non-scarring alopecia; mutation in K14    Dowling-Degos syndrome – K5 mutation    Dyskeratosis congenita – mutation in DKC1   Naegeli-Franceschetti-Jadassohn syndrome    Amyloidosis cutis dyschromia   Rothmund-Thomson syndrome   Kindler’s syndrome

Henoch-Schonlein purpura

TOXINS

Dermal sinus – diastematomyelia Ped Derm 26:688–695, 2009

Amanita muscaria mushrooms – ingestion; cholinergic mushroom toxicosis; swollen lips and tongue; altered mental status, vomiting, diarrhea, incontinence, sweating, excess salivation MMWR 68:483–484, 2019

Diastematomyelia Ped Derm 26:688–695, 2009

Arsenic poisoning – garlicky odor, severe diarrhea NEJM 370:1542– 1550, 2014

Ischemic bowel disease – abdominal pain and bloody diarrhea Jejunoileal or jejunocolic bypass – leukocytoclastic vasculitis Mesenteric artery thrombosis Vasculitis

DIMPLES Int J Dermatol 53:789–797, 2014; Curr Prob in Dermatol 13:249– 300, 2002; Ped Derm 10:16–18, 1993

CONGENITAL MALFORMATIONS

Dimple of Venus – overlying sacroiliac joints Infantile hemangioma – blue blush of sacrum with pit – dermo sacral fistula Ped Derm 37:40–51, 2020 Intrauterine big toenail imprints Ped Derm 37:226–227, 2020

Ciguatera fish poisoning – marine algae (Gambierdiscus toxicus) sea bass, grouper, red snapper, barracuda, amberjack, surgeonfish (herbivorous species that consume coral); flushing, diarrhea, vomiting, abdominal pain, pruritus, temperature reversal, dysesthesia, diffuse tingling pain, burning tongue, gingiva, teeth, myalgia, weakness, vomiting, dysesthesia, and ataxia; ciguatoxin produced by coral reef dinoflagellate plankton species ingested by herbivorous fish; incubation period is 15 minutes to 3 hours JAAD 55:193– 208, 2006

Maternal rubella syndrome Curr Prob in Dermatol 13:249–300, 2002

Scombroid fish poisoning- incubation period is 10 to 30 minutes; fish tastes tangy, hot, bitter, spicy, peppery; headache, nausea, sweating, oral burning, abdominal pain, diarrhea, vomiting, and urticaria; scombroid mackerel-like fish include tuna, skipjack, bonito, albacore, and mackerel; non-scombroid fish include herring, sardine, pilchard, anchovy, mahimahi, bluefish, marlin, amberjack, yellowtail, kahala, kahawai, mahimahi AD 115:963–965, 1979; and Japanese saury, Western Australian salmon Med J Aust 157:748– 751, 1992

INFECTIONS

Potato poisoning – rash of lower abdomen and medial thighs consisting of red papules which progress to pustules and crusted lesions; facial and abdominal edema; headache, vomiting, diarrhea J R Coll Physicians Edinb 36:336–339, 2007

Spina bifida occulta (occult spinal dysraphism) Ind J Pediatr 66:697–705, 1999; Am J Roentgenol 171:1687–1692, 1998; Clin Pediatr 34:650–654, 1995; dermoids and dermal sinus tracts of the spine Neurosurg Clin N Am 6:359–366, 1995; sacral dimples Curr Prob in Dermatol 13:249–300, 2002

Dental sinus – personal observation Congenital rubella syndrome – patella

METABOLIC DISEASES Hypophosphatasia – associated with aberrant positioning during fetal life Dermatologica 178:179–180, 1989 Mucopolysaccharidosis IV – sacral dimple

Thallium – anagen effluvium JAAD 50:258–261, 2004; nausea, vomiting, stomatitis, painful glossitis, diarrhea; severe dysesthesias and paresthesias in distal extremities, facial rashes of cheeks and perioral region, acneiform eruptions of face, hyperkeratosis of palms and soles, hair loss, Mees’ lines AD 143:93–98, 2007

NEOPLASTIC DISEASES

TRAUMA

Eccrine nevus – pigmented patch, depressed nodule, and/or linear papules JAAD 51:301–304, 2004; Acta DV (Stockh) 82:154–156, 2002

Heat urticaria – urticarial, angioedema, weakness, wheezing, headache, flushing, nausea and vomiting, diarrhea, tachycardia, syncope BJD 175:473–476, 2016 Radiation enteritis – radiation dermatitis VASCULAR DISEASES Cholesterol emboli

Carcinoma of the breast (primary) – puckered nipple Dermatofibroma, facial – extending to buccinator muscle Desmoid tumor – underlying Becker’s nevus of shoulder AD 146:1408–1412, 2010

Ectopic or christomatous salivary gland (heterotopic salivary gland tissue) – skin colored nodule along lower surface of the sternocleidomastoid muscle JAAD 58:251–256, 2008 Infantile myofibromatosis Australas J Dermatol 41:156–161, 2000 Polypoid eccrine nevus – coccygeal papule overlying a depression BJD 157:614–615, 2007

Doughy Skin

PRIMARY CUTANEOUS DISEASES Acquired cheek dimple – gingivobuccal fibrous band AD 117:811– 812, 1981 Acromial dimples – autosomal dominant Ped Derm 31:363–367, 2014; Hum Genet 76:206, 1987; sporadic Ped Derm 31:363–367, 2014

275

Mesomelic shortening of the upper extremities with spur formation with cutaneous dimpling Pediatr Radiol 28:794–797, 1998 Metaphyseal chondrodysplasia – associated with aberrant positioning during fetal life

Familial facial dimples Curr Prob in Dermatol 13:249–300, 2002

Microphthalmia with linear skin defects (MIDAS syndrome) (MLS syndrome, Xp deletion syndrome, Xp 22.3 microdeletion syndrome) – Xp22.3 deletion – X-linked dominant; linear jagged skin defects of scalp, face, neck, and occasionally upper trunk, Blaschkoesque depressed patches of face, pre-auricular ear pit, severe short stature, congenital heart defects, agenesis of the corpus callosum, ambiguous genitalia, nail dystrophy Ped Derm 25:548–552, 2008; Ped Derm 20:153–157, 2003

Faun tail nevus – personal observation

Miller-Dieker syndrome – sacral dimple

Lip pits Ann Plast Surg 45:658–661, 2000

Nail patella syndrome – dimples over area of absent patella

Popliteal dimples – personal observation

Nevoid basal cell carcinoma syndrome – dimpling over 4th knuckle

Preauricular pit – personal observation

Popliteal pterygium syndrome – shoulder dimples

Sacral dimples – sacrococcygeal or coccygeal dimples or pits

Pretibial dimples – with multiple osseous defects Lancet 10;2(7715):98, 1971

Cheek dimples Am J Med Genet 36:376, 1990 Chin dimple Coccygeal pits Pediatrics 105:E69, 2000 Elbow dimples – personal observation

Scapular (shoulder) dimple – autosomal dominant Ped Derm 10:16–18, 1993 Tibial dimple – campomelic dwarf

Prune belly syndrome – elbows and knees Robinow syndrome – sacral dimple Russell-Silver dwarfism – shoulder dimples

SYNDROMES Albright’s hereditary osteodystrophy – dimpling over the 4th and 5th metacarpophalangeal joints; brachymetatarsia; short stature, round facies, brachydactyly, obesity, atrophic pink patches with white papules of ossification; ossification of cutaneous and subcutaneous tissues, endocrine abnormalities (hypocalcemia, hyperphosphatemia); mutation in GNAS1 (gene encoding adenylate cyclase-stimulating G alpha protein) NEJM 367:2527, 2012; BJD 162:690–694, 2010; Medicine 75 (4):171–184, 1996; Endocrinology 30:922–932, 1942 Apert’s syndrome – knuckle, acromial (shoulder), and elbow dimples Ped Derm 31:363–367, 2014; Cutis 52:205–208, 1993 Arthrogryposis – multiple congenital dimples over multiple joint sites; associated with aberrant positioning during fetal life Curr Prob in Dermatol 13:249–300, 2002 Bloom’s syndrome – sacral dimple Campomelic dysplasia – pretibial skin dimple; associated with aberrant positioning during fetal life

Say syndrome – acromial dimples Ped Derm 31:363–367, 2014 Simosa craniofacial syndrome – facial dimples Smith-Lemli-Opitz syndrome – sacral dimple Curr Prob in Dermatol 13:249–300, 2002 Trisomy 9p – shoulder dimples 22q deletion syndrome – nasal dimple Weaver syndrome – facial dimples Whistling face syndrome – H-shaped chin Wolf-Hirschhorn syndrome – preauricular and sacral dimples X-linked dysmorphic syndrome with mental retardation – sacral dimple Zellweger syndrome – sacral dimple

TRAUMA

Carpenter’s syndrome – sacral dimple (pilonidal dimple)

Amniocentesis – dimple-like scars AD 135:697–703, 1999; JAAD 18:239–259, 1988

Caudal dysplasia syndrome

Intramuscular injection site

Chromosome 18q deletion syndrome – acromial dimple Dubowitz’s syndrome – sacral dimple 18q deletion syndrome – acromial (shoulder) dimples Ped Derm 31:363–367, 2014;

VASCULAR LESIONS PHACES syndrome – sternal depression BJD 155:192–194, 2006

FG syndrome – sacral dimple 4p deletion syndrome Freeman Sheldon syndrome – H-shaped dimpling of the shin Frontonasal dysplasia – nasal midline groove with blind dimples Genitopatellar syndrome – knee dimple Hypophosphatasia – skin covered spurs from forearms and legs Joubert syndrome Kabuki syndrome – preauricular dimple Kyphomelic dysplasia – associated with aberrant positioning during fetal life

DOUGHY SKIN Normal variant Cretinism Ehlers-Danlos syndrome, classic type Weaver syndrome – overgrowth syndrome with hypertonic muscles, exaggerated reflexes, micrognathia, thin hair, loose skin, low hoarse cry, soft doughy skin Am J Genetics 161A:2972–2980, 2013

276 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Arterial tortuosity syndrome – severe and widespread arterial tortuosity of aorta and middle sized arteries, increased risk of dissection and aneurysm Menkes syndrome – rare X-linked recessive, lethal, neuro-degenerative disorder of impaired copper transport, hypopigmented wiry hair, doughy skin Myxedema Acromegaly Eur J Clin Invest 356:133–139, 2005 Mastocytosis, bullous, generalized infiltrative (xanthelasmoidea) Indian J Ped 7:261–263, 2004; erythrodermic Cutis 49:189–192, 1992; thickened doughy yellow skin with bullae

Lichenoid drug eruption – crystal methamphetamine Cutis 50:193–194, 1992 Serum sickness like reaction – amphetamine NY State J Med 71:2643–2646, 1971 Stevens-Johnson syndrome – cocaine JAAD 43:97–98, 1994 Toxic epidermal necrolysis – heroin contaminants Med Clin 94:799, 1990 (Barcelona) Urticaria – heroin AD 104:80–86, 1971; cocaine Ann Emerg Med 34:296–297, 1999

Hypopituitarism Eur J Endocrinol 148:609–617, 2003

EXOGENOUS AGENTS

Abdominal tuberculosis – fever, weight loss, abdominal pain and doughy abdomen Scand J Gastroenterol 36:528–532, 2001

Cannabis – marijuana, pot, weed

Gadolinium deposition disease

 RUG ABUSE, CUTANEOUS D MANIFESTATIONS Clin Inf Dis 61:1840–1849, 2015; JAAD 69:135–142, 2013; BJD 150:1–10, 2004; Br J Surg 83:1329–1334, 1996

AUTOIMMUNE DISEASES Hypersensitivity reactions  Urticaria   Morbilliform eruptions   Fixed drug eruption   Toxic epidermal necrolysis   Serum sickness-like reaction Pemphigus vegetans, Neumann variant – INTRANASAL HEROIN JAAD 39:872–875, 1998 Scleroderma – cocaine BJD 150:1–10, 2004; South Med J 91:961–963, 1998; Rev Rheum 65:157–158, 1998; JAAD 10:525, 1984

DRUG-INDUCED Acute generalized exanthematous pustulosis – COCAINE AD 143:430–431, 2007 Angioedema – cocaine Ann Emerg Med 34:296–297, 1999 Cocaine (coke, C, snow, flake, blow)  Halitosis   Lip smacking, cuts and burns on lips   Madarosis (loss of lateral eyebrows)   Palmar and digital hyperkeratosis   Destruction of nasal septum   Snorter warts – transmission of HPV on dollar bills  Drug reactions – acute generalized exanthematous pustulosis; Stevens-Johnson syndrome   Formication – neurotic excoriations   Levamisole ANCA+ vasculitis   Vasculitis – palpable purpura   Nasal septal and palatal perforations  Pneumonitis (“crack lung”) – fever, dyspnea, pleuritic chest pain, hemoptysis Clin Inf Dis 61:1840–1849, 2015 Fixed drug eruption – cocaine, heroin Clin Inf Dis 61:1840–1849, 2015; AD 104:80–86, 1971

Cocaine – snow, flake, blow Ecstasy  Ecstasy pimples – acneiform eruption Dermatology 197:171–173, 1998   Guttate psoriasis Heroin (smack, H, ska, junk) AD 104:80–86, 1971  Urticaria   “High pruritus” – severe pruritus of genitals and face   Penile ulcers   Necrotizing cellulitis of scrotum   Pemphigus vegetans   Fixed drug eruptions   Toxic epidermal necrolysis   Necrolytic migratory erythema   Pseudoacanthosis nigricans DermNet NZ 2014 Injection marks Forensic Sci Inti 40:15–24, 1989 Levamisole-contaminated cocaine – snorting, injection, smoking Clin Inf Dis 61:1840–1849, 2015  Ecchymoses, bullae, stellate lesions with red borders and necrotic center; especially on ears and cheeks   Fixed drug eruptions   Lichen planus  Ulceration   Morbilliform exanthema   Hemorrhagic bullae   Acute kidney failure Necrotizing ulcers BJD 150:1–10, 2004  Cocaine Acta DV 76:239–241, 1996   Morphine sulfate  Quinine Methamphetamine (speed, meth, chalk, ice, crystal, crank, glass); amphetamine (crosses, hearts, magnums, reds, speed, twentytwenty, white crosses, white mole) Ann Int Med 119:1017–1028, 1993  Xerosis  Pruritus   Intense body odor JAAD 69:135–142, 2013   Grayish dry leathery skin with strange odor  Hyperhidrosis   Meth mouth – enamel erosions starting at gum line  Formication   Acne excoriee   Lichenoid drug eruptions Nodules – Red nodules; cocaine JAAD 21:570–572, 1989 Ulcerated nodules – heroin NEJM 277:473–475, 1967 Penile and scrotal necrotizing ulcers Br J Plast Surg 52:324–325, 1999; Cutis 29:62–64, 1982; J Urol 136:111–113, 1986; AD 107:121–122, 1973

Drug Abuse, Cutaneous Manifestations 277 Pentazocine (Talwin) Puffy hand syndrome – camptodactylia – fibrotic scars, inability to flex or extend fingers Addiction 101:1347–1351, 2006; J Bone Joint Surg Am 54:629–633, 1972; NEJM 273:1167, 1965

INFECTIONS AND INFESTATIONS Abscesses Clin Inf Dis 33:35–40, 2001; Clin Inf Dis 20(Suppl2):S279–282, 1995   Abscess – risk factors for infection include:   Skin popping   Non-sterile needles    Speedball injections (heroin and cocaine)    Booting (drawing back into dirty needles)    Staphylococcus aureus    Group A Streptococcus    Other streptococci    Enteric organisms    Anaerobic organisms    Oral flora    Fungi (Candida)    Polymicrobial   Aerobic organisms   Staphylococcus aureus   Streptococcus milleri  Anaerobes   Actinomyces odontolyticus   Fusobacterium nucleatum   Pigmented Prevotella   Peptostreptococcus   Veillonella   Facultative gram-negative bacteria Anthrax – heroin skin popping; edema, necrosis, blistering, compartment syndrome, necrotizing fasciitis; abdominal pain, nausea, vomiting; meningitis, intracranial hemorrhage Clin Inf Dis 61:1840–1849, 2015; Lancet 356:1574–1575, 2000 Bacteremia   50% due to Staphylococcus aureus  Sources:   Cutaneous infections   Septic thrombophlebitis   Endocarditis  Endocarditis   Right-sided   Purpura, pustules, limb ischemia due to peripheral embolism and septic vasculitis   Septic arthritis    Costochondral articulations most commonly involved    Sequela of bacteremia Systemic candidiasis – cocaine ulcers; painful nodules and pustules in hair bearing regions; chorioretinitis, uveitis; sternoclavicular septic arthritis Clin Inf Dis 15:910–923, 1992; J Infect Dis 152:577–591, 1985; NEJM 289:616–618, 1973; disseminated Candida from brown heroin (yeast overgrowth in the lemon juice used to dissolve heroin); osteoarticular (costochondral) Cellulitis – Staphylococcus aureus, Group A streptococci, enteric organisms, anaerobes, oral flora, fungi, polymicrobial infections JAAD 69:135–141, 2013  Cellulitis   Staphylococcus aureus   Group A Streptococcus   Other streptococci   Enteric organisms   Anaerobic organisms

  Oral flora   Fungi (Candida)   Polymicrobial Cervical cellulitis – neck injection Ear Nose Throat J 75:670–676, 1996; descending cervical cellulitis and mediastinitis Ann Thorac Surg 65:1483–1488, 1998 Clostridia botulinum – skin popping of black tar heroin; cellulitis, necrotizing fasciitis, gas gangrene Clin Inf Dis 61:1840–1849, 2015; wound botulism Clin Inf Dis 104:80–86, 1971 Clostridium novyi Clin Inf Dis 61:1840–1849, 2015 Clostridium perfringens Clin Inf Dis 61:1840–1849, 2015 Clostridium sordellii Clin Inf Dis 61:1840–1849, 2015 Clostridium tetani – tetanus MMWR 47:149–151, 1998 Ecthyma gangrenosum – of penis Urology 34:109–110, 1989 Femoral triangle – deep groin infection NYS J Med 84:596–598, 1984 Gas gangrene Eur J Vasc Surg 6:565–566, 1992; Br Med J 303:240–242, 1991 Mediastinitis – neck vein injection Ann Thor Surg 65:1483–1488, 1998 Mycotic aneurysm BJD 150:1–10, 2004  Arterial pseudoaneurysm Br J Surg 83:1329–1334, 1996; Dur J Vasc Surg 6:434–437, 1992   Staphylococcus aureus   Pseudomonas aeruginosa   Venous pseudoaneurysm Br J Surg 83:1329–1334, 1996   Staphylococcus aureus   Escherichia coli   Streptococcus species Necrotizing fasciitis BJD 150:1–10, 2004   Clostridium novyi Morb Mortal Wkly Rep 49:543–545, 2000   Clostridium perfringens Arch Intern Med 162:517–522, 2002   Clostridium sordellii Arch Intern Med 162:517–522, 2002   Clostridium species Necrotizing fasciitis – risk factors include;   Subcutaneous injection   Clostridium novyi   Clostridium perfringens   Other Clostridium Necrotizing ulcers Acta DV 76:239–241, 1996; BJD 150:1–10, 2004   Streptococcal species Acta DV 76:239–241, 1996 Pyoderma BJD 150:1–10, 2004 Sepsis – Candida species, Lactobacillus, Corynebacteria, Bacillus anthracis, Enterobacter agglomerans (cotton fever), non-tuberculous mycobacteria Clin Inf Dis 61:1840–1849, 2015 Septic thrombosis BJD 150:1–10, 2004; Postgrad Med J 76:561– 565, 2000   Staphylococcus aureus Staphylococcus aureus – soft tissue infections Clin Inf Dis 61:1840– 1849, 2015 Streptococcus pyogenes – soft tissue infections Clin Inf Dis 61:1840–1849, 2015 Thrombophlebitis BJD 150:1–10, 2004 Ulcerations AD 104:80–86, 1971

INFLAMMATORY DISORDERS Cheilitis AD 104:80–86, 1971 Dermal fibrosis – pentazocine BJD 150:1–10, 2004

278 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Granuloma – talc or cornstarch Arch Intern Med 123:656–659, 1969

Skin tracks – shooting tattoo AD 104:80–86, 1971

Hyperpigmentation NY State J Med 71:2643–2646, 1971

Tattoos AD 104:80–86, 1971

Panniculitis BJD 150:1–10, 2004

Thermal burns AD 104:80–86, 1971

Sclerosis BJD 150:1–10, 2004

Tourniquet hyperpigmentation AD 104:80–86, 1971

Serotonin syndrome – tachycardia, hypothermia; Ecstasy or Molly Clin Inf Dis 61:1840–1849, 2015

Woody expansive fibrosis, hard skin JAMA 238:1542–1543, 1977; irregularly shaped ulcers extending deep into subcutaneous tissue and muscle JAAD 2:47–55, 1980; multiple depressed atrophic scars JAAD 22:694–695, 1990

METABOLIC DISORDERS Gastroenteritis – swallowing bags of narcotics or cocaine Clin Inf Dis 61:1840–1849, 2015 Gynecomastia Hyperemesis syndrome – marijuana; periods of nausea, vomiting, abdominal pain; compulsive bathing Clin Inf Dis 61:1840–1849, 2015 High pruritus – heroin; immediately following injection for 2–4 hours; skin flushing, dry mouth, watery eyes, runny nose AD 104:80–86, 1971 Meningitis, encephalitis, neurologic syndromes Clin Inf Dis 61:1840–1849, 2015

PRIMARY CUTANEOUS DISEASE Acneiform dermatosis – “ecstasy pimples”; papules and pustules of face; ECSTASY (N-methyl-3,4 methylenedioxyamphetamine, MDMA) Dermatology 197:171–173 Body odor – methamphetamine JAAD 69:135–141, 2013

VASCULAR DISEASES Cannabis arteritis – necrosis of lower limbs (form of thromboangiitis obliterans) Clin Inf Dis 61:1840–1849, 2015; BJD 152:166–169, 2005 Chronic venous insufficiency – occlusive thrombophlebitis of forearms with lymphedema; septic thrombophlebitis with mycotic aneurysm Res Nurs Health 24:423–432, 2001 Digital necrosis – cocaine BJD 150:1–10, 2004; Ann Intern Med 133:923–924, 2000 False aneurysm   Injection marks   Intra-arterial injections   Mycotic aneurysm Femoral pseudoaneurysm World J Surg 21:783–786, 1997 Levamisole-induced ANCA-positive vasculopathy – earlobes and cheeks Ann Intern Med 151:758–759, 2010 Nasal septum perforation

Hyperhidrosis – methamphetamine JAAD 69:135–141, 2013

Panarteritis – purpura fulminans, mononeuritis multiplex, cardiac, gastrointestinal involvement; cocaine; cannabinoids, methamphetamines Intensive Care Med 25:113–117, 1999; necrotizing angiitis NEJM 283:1003–1011, 1970

Hyperkeratosis – palmar and digital Cutis 44:223–225, 1989

Polyarteritis nodosa NEJM 283:1003–1011, 1970

Hyperpigmentation NY State J Med 71:2643–2646, 1971

Puffy hand syndrome – due to lymphatic obstruction and destruction AD 142:1084–1085, 2006; J Bone Joint Surg Am 54:629–633, 1972; AD 104:80–86, 1971; NEJM 273:1167, 1965

Enamel erosions starting at gum line (“meth mouth”) – methamphetamine Oral Dis 15:27–37, 2009

Necrolytic migratory erythema – heroin Dermatology 189:72–74, 1994 Pseudoacanthosis nigricans – heroin AD 104:80–86, 1971 Psoriasis – ecstasy Aust J Derm 45:167–169, 2004 Xerosis – methamphetamine JAAD 69:135–141, 2013

PSYCHOCUTANEOUS DISORDERS

Raynaud’s phenomenon – cocaine BJD 150:1–10, 2004; South Med J 91:961–963, 1998 Thrombophlebitis Vasculitis – cocaine JAAD 69:135–141, 2013; Ann Int Med 133:923–924, 2000 Cannabis (marijuana, pot, weed)

Acne excoriee AD 104:80–86, 1971 Excoriations AD 104:80–86, 1971

TRAUMA

DYSCHROMATOSIS (HYPOPIGMENTATION AND HYPERPIGMENTATION)

BULLAE False aneurysm Eur J Surg 165:505–506, 1999

JAAD 33:835–836, 1995

Injection marks Forensic Sci Inti 40:15–24, 1989  Injection sites by duration of intravenous drug use – initiation; cubital fossa; 3–5 years – upper arms; 4 years – hands; 6 years – neck, foot, leg; 10 years – groin, toes, fingers Drug Alcohol Depend 62:77–82, 2001

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE REGULATION

Madarosis – cocaine NEJM 314:1324, 1986

Contact leucomelanosis

“Pop” scar – atrophic, hypertrophic, keloid of extensor arms and legs; AD 104:80–86, 1971

Dermatomyositis

“Pop” nodules Scarring BJD 150:1–10, 2004

APECED syndrome BJD 178:335–349, 2018

Graft vs. host disease, chronic Ped Derm 35:343–353, 2018; JAAD 38:369–392, 1998; AD 134:602–612, 1998; AD 132:1161–1163, 1996; AD 126:1324–1329, 1990; trichrome vitiligo; vitiligo and

Dyschromatosis (Hypopigmentation and Hyperpigmentation) 279 alopecia areata in chronic graft vs host disease JAMA Derm 151:23–332, 2015

and face AD 128:966–970, 1992; macular amyloidosis – speckled brown macules BJD 167:548–554, 2012

Lupus erythematosus, neonatal, discoid lupus erythematosus JAAD 40:675–681, 1999

Urticaria pigmentosa

Mixed connective tissue disease – with photo-dyschromia Scleroderma – salt and pepper perifollicular hyperpigmentation; hyperpigmentation in sclerotic and non-sclerotic areas; hyperpigmented streaks over blood vessels on a background of depigmented skin of the legs

DRUGS Afloqualone – photoleukomelanodermatitis Ped Derm 19:523–526, 2002 Tetracycline Ped Derm 19:523–526, 2002 Thiazide diuretics Ped Derm 19:523–526, 2002

EXOGENOUS AGENTS Betel leaves – mottled hyperpigmentation evolving into confetti-like hypopigmentation JAAD 40:583–589, 1999 Facial dressings of betel pepper (piper beetle) JAAD 40:583–589, 1999 Diphenylcyclopropenone, topical (dyschromia in confetti) - hypopigmented patches with confetti hypopigmentation at sites of treatment for alopecia areata Ped Derm 19:523–526, 2002; AD 128:518–520, 1992 Monobenzyl ether of hydroquinone, topical – dyschromia with hyper- and hypo- or depigmented macules Ped Derm 19:523–526, 2002 Organochlorine exposure (agent orange) – chloracne with comedones, gray dyschromia, hypertrichosis, folliculitis, porphyria cutanea tarda, melanoma and non-melanoma skin cancer, non-Hodgkin’s lymphoma, dermatofibrosarcoma protuberans JAAD 74:143–170, 2016 Welding foreign bodies – speckled hyperpigmentation of pretibial legs AD 142:790–792, 2006

INFECTIONS AND INFESTATIONS Bejel HTLV-1 Int J Dermatol 58:953–960, 2019 Leishmaniasis – post kala-azar dermal leishmaniasis Onchocerciasis – hyper- and hypopigmentation (leopard skin) Ped Derm 33:264–274, 2016; Cutis 72:298–302, 2003; AD 120:505– 507, 1984 Pinta – generalized cutaneous phase – merging of second and third stages; tertiary Cutis 51:425–430, 1993 Syphilis – secondary; as macular syphilis fades get depigmented macules with hyperpigmented background (leukoderma syphiliticum) on back and sides of neck (necklace of Venus)

INFLAMMATORY DISORDERS Post-inflammatory dyspigmentation

METABOLIC DISEASES Congenital erythropoietic porphyria –mottled pigmentation Ped Derm 20:498–501, 2003; gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 171L422–423, 2014; BJD 167:988–900, 2012 Mixed cryoglobulinemia – personal observation Fanconi’s anemia – autosomal recessive; dyschromatosis; oral leukoplakia, oral and vulvar squamous cell carcinoma, short stature, absent radii, bone marrow failure, endocrine abnormalities, café au lait macules, guttate hypopigmentation, intertriginous hyperpigmentation, broad nose, epicanthal folds, micrognathia JAAD 54:1056–1059, 2006 Iron deficiency anemia – heterochromic scalp hair JAAD 49:1148– 1150, 2003 Kwashiorkor – protein and caloric deprivation; cracked paint; flag sign JAAD 21:1–30, 1989 Malnutrition – dyschromatosis Ped Derm 19:523–526, 2002 Pernicious anemia – diffuse or mottled of face, hands, and feet J Dermatol 28:282–285, 2001 Porphyria cutanea tarda – melasma-like; diffuse hyperpigmentation; dyschromatosis sclerodermoid PCT AD 148:1317–1322, 2012; congenital erythropoietic porphyria Semin Liver Dis 2:154–63, 1982 Whipple’s disease – cachexia with dyschromic generalized pigmentation NEJM 383:68–74, 2020

NEOPLASTIC DISEASES Generalized nevoid hyperpigmentation Lymphoma – cutaneous T-cell lymphoma; personal observation; CD8+ cutaneous T-cell lymphoma JAAD 77:489–496, 2017 Melanocytic nevus- congenital nevi Myeloma with reticulated hyperpigmentation – personal observation Nevus depigmentosus – repigmenting Nevus depigmentosus with lentiginosis JAAD 54:S238–240, 2006 Nevus spilus

PHOTODERMATOSES

Yaws

Acquired brachioradial cutaneous dyschromatosis (dermatoheliosis) Ann Dermatol 30:342–344, 2018; JAAD 42:680–684, 2000

INFILTRATIVE DISEASES

PRIMARY CUTANEOUS DISEASES

Amyloidosis cutis dyschromica – generalized reticulated hyper- and hypopigmented macules of trunk and limbs, sparing the hands, feet,

Atopic dermatitis – in the adult

Vagabond leucoderma – body lice

Blaschkoid dyspigmentation Ped Derm 31:471–476, 2014

280 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Confluent and reticulated papillomatosis Epidermolysis bullosa pruriginosa – reticulated linear hypopigmented plaques; bullae; scars; zebra stripe appearance; dyschromatosis Ped Derm 32:549–550, 2015 Epidermolysis bullosa simplex with stippled and mottled pigmentation – autosomal dominant; bullae heal without scarring, atrophy, or milia; improves with age; mottled macular pigmentation of the trunk, proximal extremities; diffuse or punctate keratoderma with nail dystrophy; mutation in EXPH5 (exophilin 5) (intracellular vesicle trafficking and exosome secretion) Gene Reviews Seattle (WA) University of Washington, Seattle, 1993–2019; JAMA Derm 152:1137–1141, 2016; Ped Derm 30:631–632, 2013; BJD 128:679– 685, 1993; Clin Genet 15:228–238, 1979 Erythromelanosis follicularis faciei et colli (keratosis rubra pilaris faciei atrophicans) – facial erythema, keratosis pilaris, follicular atrophy) – cheeks, arms, and pre-auricular area AD 147:235–240, 2011; Ped Derm 23:31–34, 2006; JAAD 34:714, 1996; JAAD 32:863–866, 1995; JAAD 25:430–432, 1991; Cutis 34:163–170, 1984; JAAD 5:533–534, 1981; BJD 102:323–325, 1980; Dermatologica 132:269–287, 1966; Hautarzt 9:391–393, 1960 Eyelash heterochromia – personal observation Idiopathic eruptive macular hyperpigmentation Ped Derm 13:274, 1996 Junctional epidermolysis bullosa of late onset (skin fragility in childhood) – speckled hyperpigmentation of elbows; hemorrhagic bullae, teeth and nail abnormalities, oral blisters, disappearance of dermatoglyphics, palmoplantar keratoderma, small vesicles, atrophy of skin of hands BJD 169:714–716, 2013 Lichen planus pigmentosus J Clin Aesthet Dermatol 9:44–50, 2016 Lichen simplex chronicus – personal observation Mosaic piebaldism – personal observation Mottled hyperpigmentation, epidermolysis bullosa, and punctate keratoses JAAD 15:1289–1291, 1986 Mottled pigmentation of neck and elbows Z Haut-u Geschl Krankh 32:33–44, 1962 Notalgia paresthetica – personal observation Piebaldism BJD 132:929–935, 1995 Riehl’s melanosis – gray-brown reticulated hyperpigmentation J Drugs in Dermatol 13:356–358, 2014 Scalp hair heterochromia, linear Ped Derm 31:733–734, 2014 Segmental confetti dyschromatosis Photoderm Photoimmunol Photomed 29:266–267, 2013 Universal acquired melanosis (carbon baby) Vitiligo

SYNDROMES Acrogeria (Gottron’s syndrome) – micrognathia, atrophy of tip of nose, atrophic skin of distal extremities with telangiectasia, easy bruising, mottled pigmentation or poikiloderma of extremities, dystrophic nails BJD 151:497–501, 2004; BJD 103:213–223, 1980; Arch Dermatol Syphiligr 181:571–583, 1941 Acromelanosis albo-punctata (Siemen’s) Acropigmentation symmetrica of Dohi (dyschromatosis symmetrica hereditaria) – autosomal dominant, sporadic; Asians with onset under 20 years of age; acral hyperpigmentation (reticulate pattern becoming patches with hypopigmented macules of face, trunk, distal extremities); mottled pigmentation with patchy depigmentation of the back, hands, and feet, sometimes arms and legs; freckle-like macules of the face; pigmentation is lifelong; ADAR1 mutation

(encodes adenosine deaminase) acting on RNA1 p150 isoform Indian J Dermatol 57:42–44, 2012; BJD 169:637–644, 2013; JAAD 63:529–530, 2010; AD 141:193–196, 2005; BJD 150:633–639, 2004; BJD 144:162–168, 2001; JAAD 43:113–117, 2000; Jpn J Dermatol 27:95–96, 1929; sun-exposed areas only JAAD 10:1–16, 1984 Anonychia with bizarre flexural pigmentation – autosomal dominant, absent nails, dry peeling palmoplantar skin, coarse and sparse frontal hair; mottled hyper- and hypopigmentation of the axillae, groin, and natal cleft BJD 92:469–474, 1975 Apert’s syndrome – autosomal dominant; FGFR-2 mutation; craniosynostosis with midfacial malformation; cone shaped calvarium, proptosis, hypertelorism, short nose with bulbous tip; high arched palate; lips bow-shaped, unable to form a seal; telangiectasias of face and bulbar conjunctiva, often in butterfly distribution; mottled hyperpigmentation, hypopigmentation and poikiloderma; seborrheic dermatitis, atopic dermatitis, and xerosis common Am J Med Genet 44:82–89, 1992; severe pustular acne at puberty Ped Derm 20:443–446, 2003 Ataxia telangiectasia – telangiectasias of bulbar conjunctivae, tip of nose, ears, antecubital and popliteal fossae, dorsal hands and feet; atrophy with mottled hypo- and hyperpigmentation, dermatomal CALMs, photosensitivity, canities, acanthosis nigricans, dermatitis; cutaneous granulomas present as papules or nodules, red plaques with atrophy or ulceration JAAD 10:431–438, 1984; Ann Int Med 99:367–379, 1983 Atypical progeroid syndrome – autosomal recessive; diffuse mottled hyperpigmentation, foot ulcers, facial dysmorphism, recurrent infections, intellectual disability; prolidase deficiency; peptidase D deficiency Ped Derm 36:913–917, 2019; Ped Derm 36:926–928, 2019 Berlin syndrome – no vellus hairs; mottled pigmentation and leukoderma, flat saddle nose, thick lips, fine wrinkling around eyes and mouth (similar to Christ-Siemens ectodermal dysplasia); stunted growth, bird-like legs, mental retardation Dermatologica 123:227–243, 1961 Chediak-Higashi syndrome – speckled hyper- and hypopigmentation in sun-exposed areas; pyogenic infections; lysosomal trafficking regulator gene (Lyst); defective microtubule-mediated lysosomal transfer Ped Derm 34:607–608, 2017; JAAD 49:S244–246, 2003 Congenital dyschromia with erythrocyte, platelet, and tryptophan metabolic abnormalities JAAD 19:642–655, 1988 Da Costa’s syndrome Dermatopathia pigmentosa reticularis – generalized reticulate hyperpigmentation; sweating disorders, decreased dermatoglyphics, alopecia, onychodystrophy, palmoplantar keratoses JAAD 50:S65– 69, 2004 Dowling-Degos disease (reticulated pigmented anomaly of the flexures) – autosomal dominant; females mostly affected; dyschromatosis (reticulated pigmentation of axillae, groin, and other intertriginous areas), pitted atrophic scars at corners and around mouth, freckles of vulva, comedo-like lesions BJD 147:568–571, 2002; JAAD 40:462–467, 1999; Clin Exp Dermatol 9:439–350, 1984; generalized Dowling-Degos disease – hyper- and hypopigmented, and erythematous macules JAAD 57:327–334, 2007 Dyschromatosis universalis hereditaria – mottled hyperpigmentation, small stature, high tone deafness Ped Derm 24:566–570, 2007; Semin Cut Med Surg 16:72–80, 1997; Clin Exp Derm 2:45, 1977 Dyschromatosis universalis hereditaria – autosomal dominant, hyperpigmented macules in seborrheic regions, achromic macules or diffuse hypopigmentation, leukotrichia Ped Derm 19:523–526, 2002; Ped Derm 17:70–72, 2000; BJD 85:66–70, 1971

Dyschromatosis (Hypopigmentation and Hyperpigmentation) Dyskeratosis congenita (Zinsser-Cole-Engmann syndrome) – X-linked recessive – cutaneous atrophy and pigmentation; mental retardation, short stature, deafness, conjunctivitis with obstruction of lacrimal ducts, blepharitis, palmoplantar keratoderma, palmoplantar hyperhidrosis, urethral anomalies, esophageal stenosis, choanal atresia, hepatic abnormalities, frontal lobe atrophy, intracranial calcifications, hypogonadism, osteoporosis, avascular necrosis Ped Derm 26:176–179, 2009; J Med Genet 12:339–354, 1975; autosomal dominant dyskeratosis congenital – personal observation; severe form with aplastic anemia, hemophagocytic syndrome is Hoyeraal-Hreidarsson syndrome SKINmed 12:117–118, 2014 Familial gigantic melanocytosis (familial melanopathy with gigantic melanocytes) – autosomal dominant; diffuse brown hyperpigmentation with raindrop hypopigmentation, guttate hypomelanosis; light colored scalp and body hair; sparse pubic and axillary hair; large melanocytes filled with late stage melanosomes J Cut Pathol 45:918–922, 2018; Int J Derm 44:1010–1015, 2005; Am J Dermatopathol 6:31–34, 1984 Familial hyper- and hypopigmentation – hypopigmentation, hyperpigmentation, lentigines, café au lait macules; mutation in KITLG (kit ligand) BJD 175:1369–1371, 2016 Fanconi’s syndrome (pancytopenia with congenital defects) – generalized olive-brown hyperpigmentation, especially of lower trunk, flexures, and neck with depigmented macules (rain-drop like); hypoplastic anemia, slender build, short broad thumbs, tapered fingers, microcephaly, hypogonadism BJD 164:245–256, 2011; Semin Hematol 4:233–240, 1967 Generalized mottled pigmentation with postnatal blistering JAAD 50:S65–69, 2004 Griscelli syndrome – autosomal recessive; dyschromatosis with silvery hair, hypopigmented or normal color skin or bronze-like diffuse tanning on sun-exposed areas; dyschromatosis similar to familial gigantic melanocytosis J Cut Pathol 45:918–922, 2018 Haber’s syndrome – persistent facial erythema, telangiectasias with mild induration, similar to rosacea; darkly pigmented black keratotic papules of axilla, neck, torso; pitted scars

Mendes de Costa syndrome – generalized reticulate hyperpigmentation on face and limbs, intraepidermal blisters, microcephaly, mental retardation, atrichia, short conical fingers JAAD 50:S65–69, 2004 Mitochondrial disorders – erythematous photodistributed eruptions followed by mottled or reticulated hyperpigmentation; alopecia with or without hair shaft abnormalities including trichothiodystrophy, trichoschisis, tiger tail pattern, pili torti, longitudinal grooving, and trichorrhexis nodosa Pediatrics 103:428–433, 1999 Naegeli-Franceschetti-Jadassohn syndrome – autosomal dominant, punctate hyperpigmentation, waist, axillae, neck; hypohidrosis, palmoplantar hyperkeratosis; tooth enamel hypoplasia and nail anomalies JAAD 28:942–950, 1993; Clin Exp Dermatol Jun;1(2):127–140, 1976 Pallister-Killian syndrome – short neck; streaks of hypo- and hyperpigmentation, mental retardation, coarse facies with prominent forehead with abnormally high anterior hairline, sparse temporal hair and sparse anterior scalp hair, hypertelorism, short nose with anteverted nostrils, flat nasal bridge, flat occiput, sparse eyelashes, long philtrum with thin upper lip, horizontal palpebral fissure, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i(12p) (tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 24:426– 428, 2007; Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005 Photoleukomelanodermatitis of Kobori – dyschromic drug eruption after treatment with afloqualone, thiazides, tetracycline and ultraviolet exposure Piebaldism – depigmented patches with hyperpigmented macules adjacent to or within Ped Derm 36:72–84, 2019 Reticulate acropigmentation of Kitamura – reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation of dorsal hands and feet; pigmentation may spread to limbs, neck, and forehead; ADAM10 mutation BJD 177:945–959, 2017; palmar pits J Dermatol 27:745–747, 2000; JAAD 40:462–467, 1999

HOPP syndrome – hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, lingua plicata, onychogryphosis, ventricular arrhythmias, periodontitis BJD 150:1032–1033, 2004; BJD 147:575–581, 2002

Unilateral dermatomal pigmentary dermatosis – segmental dyschromatosis JAAD 27:763–764, 1992

Hutchinson-Gilford syndrome (progeria) – mottled hyperpigmentation Am J Med Genet 82:242–248, 1999; J Pediatr 80:697–724, 1972; initial changes include alopecia, sclerodermoid changes of chest and abdomen, prominent superficial veins and dyspigmentation JAMA Derm 150:197–198, 2014

Werner’s syndrome (pangeria) – mottled hyperpigmentation Medicine 45:177–221, 1966

Immuno-osseous dysplasia – short-limbed dwarfism, immunodeficiency, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation) Ped Derm 23:373–377, 2006 Incontinentia pigmenti JAAD 50:S65–69, 2004 Kindler’s syndrome – acral bullae in infancy; progressive poikiloderma with photosensitivity; nail dystrophy, webbing of digits, esophageal and urethral stenosis, ectropion, poor dentition, gingival fragility, aged hands with fine wrinkling and scarring, hyperkeratosis of hands and palms and soles, dyspigmentation, diffuse telangiectasias, hyp short arm chromosome 20; Kind 1; actin cytoskeletonextracellular matrix interactions (membrane associated structural and signaling protein Ped Derm 23:586–588, 2006; AD 142:620– 624, 2006; BJD 66:104–111, 1954 LUMBAR syndrome – patch of hypo- and hyperpigmentation with atrophic macule Ped Derm 37:78–85, 2020

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Wende-Bauckus/Pegum – zones of normal, yellow-bronze, and black patches of hyperpigmentation; white macules of trunk

Westerhof syndrome – hereditary congenital hypopigmented and hyperpigmented macules BJD 161:1399–1400, 2009; Curr Prob in Derm VII:143–198, 1995; AD 114:931–936, 1978 X-linked reticulate pigmentary disorder with systemic manifestations (familial cutaneous amyloidosis) (Partington syndrome II) – X-linked; rare; Xp21-22; boys with generalized reticulated muddy brown pigmentation (dyschromatosis) with hypopigmented corneal dystrophy (dyskeratosis), coarse unruly hair, unswept eyebrows, silvery hair, hypohidrosis, recurrent pneumonia with chronic obstructive disease, clubbing; failure to thrive, female carriers with linear macular nevoid Blascko-esque hyperpigmentation Ped Derm 22:122–126, 2005; Semin Cut Med Surg 16:72–80, 1997; Am J Med Gen 10:65:1981 Xeroderma pigmentosum Ped Derm 19:523–526, 2002; resembling dyschromatosis symmetrica hereditaria Ped Derm 3:410–413, 1986 Ziprkowski-Margolis syndrome – X-linked recessive; pigmentary dilution of hair and skin, sparing buttocks and genital areas; later multiple hyperpigmented macules with leopard-like appearance; deaf-mutism, heterochromic irides

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

TOXINS

Graft vs. host reaction, chronic AD 134:602–612, 1998

Arsenic – diffuse pigmentation, especially of trunk; with depigmentation yielding rain-drop appearance (freckled raindrop pattern) (“raindrops on a dusty road”); arsenic toxicity due to contaminated ground water consumption; especially in Bangladesh and West Bengal, India; also in India, Argentina, China, Chile, Thailand, and Mexico SkinMed 11:211–216, 2013; Dermatol Clinics 29:45–51, 2011; Cutis 80:305–308, 2007; J Envir Sci Health Part A Tox Hazard Subst Environ Eng 38:141:163, 2003

Immune reconstitution inflammatory syndrome Dermatol Online J 11:31, 2005

Mustard gas AD 128:775–780, 1992

TRAUMA Burns 26:581–586, 2000 Radiation dermatitis, chronic Acta DV 49:64–71, 1969

 IFFUSE FRECKLE-LIKE OR RETICULATE D HYPERPIGMENTATION OF DORSAL ASPECTS OF HANDS AND FEET, EXTREMITIES OR FLEXURES DERMATOL RES PRACT 2017:3518568

Linear IgA disease Clin Exp Dermatol 13:85–86, 1988 Linear IgA/IgG bullous dermatosis – dyshidrosiform bullae of palms, herpetiform bullae, cutaneous erosions, tongue erosions JAMA Derm 149:1308–1313, 2013 Pemphigoid gestationes AD 143:1168–1172, 2007; Clin Exp Dermatol 13:85–86, 1988 Pemphigus vulgaris Dermatol 16:10, 2010; Cutis 35:445–446, 1985 Still’s disease – adult onset Still’s disease – vesicopustules of hands and feet J Eur Acad Dermatol Venereol 19:360–363, 2005

DEGENERATIVE DISEASES Syringomyelia – segmental dyshidrosis J Neurol Neurosurg Psychiatry 67:106–108, 1999

DRUG-INDUCED

Dermatopathia pigmentosa reticularis

Anti-PD-1 therapy (nivolumab/pembrolizumab – lichenoid eruptions, vitiligo, dermatitis, red papules with scale, red papules and nodules, inflammation surrounding seborrheic keratosis, dyshidrosiform palmar lesions, penile erosions JAMA Derm 152:1128–1136, 2016; JAAD 74:455–461, 2016

Dyschromatosis universalis hereditaria

Aspirin Acta DV 68:402–407, 1988

Epidermolysis bullosa simplex with mottled pigmentation

Drug eruption

Hereditary symmetric dyschromatosis of Dohi

DRESS associated with high IgG levels BJD 174:681–683, 2016

Naegeli-Franceschetti-Jadassohn syndrome Heterochromia extremitarum

Intravenous gamma globulin infusion (IVIG) JAAD 66:312–316, 2012; AD 142:213–217,247–248, 2006; J Drugs Dermatol 3:337– 340, 2003; Cutis 69:35–38, 2002; Neurology 54:1879, 2000; Neurology 53:1154–1155, 1999

Dowling-Degos disease

Isotretinoin – personal observation

Acromelanosis progressiva Amyloidosis cutis dyschromica

Reticulate acropigmentation of Kitamura

Mycophenylate mofetil Ann Int Med 132:417, 2000

DYSHIDROSIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – to nickel, poison ivy, preservatives, flowers Ned Tijdschrift Geneeskunde 135:1048–1049, 1991; Contact Dermatitis 23:203–204, 1990; systemic contact dermatitis – ethylenediamine; allergic contact dermatitis to henna – dyshidrosiform bullae of palm

Oral contraceptives Acta DV 68:402–407, 1988 Piroxicam Cutis 485–486, 1985 Vancomycin – giant dyshidrosis; localized palmar vancomycininduced linear IgA disease; bullae in palmar creases AD 145:603– 604, 2009

EXOGENOUS AGENTS Coffee – dyshidrotic dermatosis of coffee drinkers Cutis 40:421–422,1987

Ped Derm 28:580–581, 2011

Foreign body granulomas

Anti-cardiolipin syndrome – personal observation

Ingestions of chromium, cobalt, neomycin Curr Probl Dermatol 51:80–85, 2016

Autoantibodies to BP 230 and laminin gamma 1 – bullae of lips, periumbilical bullae, giant bullae of palms BJD 175:619–621, 2016 Autoimmune progesterone dermatitis Cutis 33:490–491, 1984 Bullous pemphigoid (dyshidrosiform pemphigoid) JAAD 67:1087– 1089, 2012; Acta DV 90:4–5, 2010; BJD 160:451–453, 2009; BJD 149:1079–1081, 2003; Hautarzt 45:97–99, 1994; JAAD 26:651–652, 1992; Clin Exp Dermatol 13:85–86, 1988; AD 115:320–321, 1979; hemorrhagic dyshidrosis Clin Exp Derm 13:342–343, 1988; anti-p200 and anti- alpha3 chain of laminin 5 JAMA Derm 152:897– 904, 2016; JAAD 52:S90–92, 2005 Dermatitis herpetiformis

Irritant contact dermatitis Metal workers exposed to oils Contact Derm 19:184–188, 1988 Phototherapy blisters Post-cast – ipsilateral dyshidrosis Arch Phys Med Rehabil 76:97– 100, 1995 Smoking Acta DV 68:402–407, 1988

INFECTIONS AND INFESTATIONS Cytomegalovirus-associated vasculitis – personal observation

Dyshidrosis Dermatophytid – associated with inflammatory tinea pedis Gypsy moth caterpillar spines Coxsackie virus – hand, foot, and mouth disease; atypical hand foot and mouth disease due to Coxsackie A6 JAMA Derm 153:219–220, 2017 Dermatophytid Herpes simplex virus JAAD 18:169–172, 1988; NEJM 314:686–691, 1986; NEJM 314:749–757, 1986; recurrent HSV Cutis 105:117, 122, 2020 Herpes zoster HIV-associated pompholyx Acta DV 87:378–379, 2007 Mosaic warts

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Lymphoma, including dyshidrosis-like eruption of adult T-cell lymphoma/leukemia Am J Dermatopathol 31:834–837, 2009; JAAD 46:S137–141, 2002; JAAD 13:213–219, 1985; CTCL JAAD 34:295–297, 1996; JAAD 47:914–918, 2002; palmoplantar pustular dermatitis of CTCL Cutis 54:202–204, 1994; leukemic CTCL AD 140:479–484, 2004; vesicular variant cutaneous T-cell lymphoma – personal observation Myxoid cysts – multiple myxoid cysts of the fingers JAAD 53:914– 916, 2005 Syringolymphoid hyperplasia (possible cutaneous T-cell lymphoma) AD 134:753–754, 1998 Woringer-Kolopp disease (pagetoid reticulosis) JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939

Mycobacterium marinum J Clin Aesthet Dermatol 11:45–51, 2018 Petechial glove and sock syndrome (Parvovirus B19) JAAD 27:835–838, 1992

PRIMARY CUTANEOUS DISEASES

Scabies Hautarzt 54:156–159, 2003

Acrodermatitis continua of Hallopeau

Smallpox

Acropustulosis of infancy AD 115:831–833, 1979

Syphilis Ped Inf Dis 31:1315, 2012

Atopic dermatitis Clin Exp Derm 12:189–190, 1987

Tinea manuum Acta DV (Stockh) 36:272–278, 1956; Trichophyton mentagrophytes from African pygmy hedgehog Cutis 105:314–316, 2020

Chronic recalcitrant pustular eruptions of the palms and soles   Acrodermatitis continua of Hallopeau   Pustular bacterid of Andrews   Pustular psoriasis   Reactive arthritis

Tinea pedis, bullous JAAD 42:132–133, 2000; Ped Derm 16:255– 258, 1999 Trichosporon cutaneum AD 129:1020–1023, 1993 Varicella – reactivation varicella (atypical varicella) BJD 151:254– 256, 2004

Dyshidrosis (pompholyx) Am J Clin Dermatol 11:305–314, 2010; ; giant dyshidrosis; dyshidrosis with secondary infection and lymphedema of hand BJD 161:177–180, 2009; Dermatitis 17:165– 181, 2006; pompholyx AD 143:1578–1580, 2007 Epidermolysis bullosa

INFILTRATIVE Primary systemic amyloidosis Clin Exp Dermatol 37:786–801, 2012 Langerhans cell histiocytosis Recurrent self-healing cutaneous mucinosis – red papules of palms and fingertips with pustules and vesicles BJD 143:650–652, 2000

Id reaction – fungal id (dermatophytid); personal observation Internal reactivation from food, drug, or haptenic (nickel) origin AD 143:1504–1508, 2007 Keratolysis exfoliativa BJD 167:1076–1084, 2012 Lichen nitidus BJD 82:423–424, 1976 Lichen planus, bullous – personal observation Lichen ruber planus Cutis 30:401–404, 1982

INFLAMMATORY DERMATOSES

Pityriasis rosea, vesicular variant SKINMed 10:116–118, 2012

Eosinophilic pustular folliculitis JAMA Derm 149:367–368, 2013

Pustular psoriasis, including palmoplantar psoriasis

Erythema multiforme

Subcorneal pustular dermatosis

Sarcoidosis

SYNDROMES METABOLIC Bile pigment deposition (dark brown and green) at sweat pores in patients with liver disease Eur Acad Dermatol Venereol 24:235–236, 2010; JAAD 26:655–656, 1992 Polymorphic dermatitis of pregnancy Ann DV 128:531–533, 2001 Pruritic urticarial papules and plaques of pregnancy (PUPPP) Ann DV 128:531–533, 2001 Tyrosinemia type II (Richner-Hanhart syndrome) – vesicles of fingertips Ped Derm 23:259–261, 2006; Dermatol 182:168–171, 1991 Acquired zinc deficiency – personal observation

NEOPLASTIC Eccrine syringofibroadenomatosis AD 130: 933–934, 1994

Klippel-Trenaunay syndrome – limb hyperplasia with lymphatic malformation of palmar skin Cutis 83:255–262, 2009 Sweet’s syndrome, pustular variant – personal observation

TRAUMA Chilblains – personal observation Friction blisters

VASCULAR DISORDERS Eosinophilic granulomatous with polyangiitis Eur J Dermatol 25:188–189, 2015

EAR, HARD (PETRIFIED AURICLES)

Hypopituitarism Indian J Endocrinol Metab 16:830–832, 2012; J Clin Endocrinol Metab 55:354–357, 1982

Condition with * denotes calcification

Hypothermia – auricular ossification JAMA Derm 152:335–336, 2016 Ochronosis

AUTOIMMUNE DISEASES Relapsing polychondritis

Ossification – auricular ossificans (ectopic ossification of the auricle) JAAD 49:142–144, 2003; Australas J Dermatol 39:268–270, 1998; Laryngoscope 95:566–576, 1985; secondary to frostbite; Addison’s disease South Med J 59:1268–1270, 1966

Scleroderma

Pretibial myxedema AD 122:85, 1986

Epidermolysis bullosa acquisita – ossification

Pseudohypoparathyroidism Pseudopseudohypoparathyroidism – calcified ears BJD 158:409– 410, 2008

DEGENERATIVE DISORDERS Chondromalacia – systemic chondromalacia (Meyenburg's disease)

NEOPLASTIC DISORDERS

Nance-Sweeney chondrodysplasia* Birth Defects 6:25–27, 1970

Exostoses Laryngoscope 95:566–576, 1985 Hypothyroidism JAAD 51:799–800, 2004; familial petrified (calcified) ears JAAD 57:S121–122, 2007

EXOGENOUS AGENTS Auricular prosthesis

Hyperthyroidism

Bluetooth device – petrified ear AD 145:1065–1066, 2009

Leukemia Lymphoma

INFECTIONS AND INFESTATIONS PARANEOPLASTIC DISORDERS

Leprosy, lepromatous – multinodular infiltrated ears Cutis 95:19, 25–26, 2015

Bazex syndrome

Lobomycosis Lyme disease

PHOTODERMATOSES Actinic damage JAAD 51:799–800, 2004

INFILTRATIVE DISORDERS Scleromyxedema (lichen myxedematosus) JAAD 44:273–281, 2001; JAAD 33:37–43, 1995

PRIMARY CUTANEOUS DISEASES Alopecia mucinosa

INFLAMMATORY DISORDERS Perichondral fibrosis and perichondritis JAMA Derm 152:335–336, 2016

Atopic dermatitis – lichenification with fibrosis – personal observation Idiopathic Clin Exp Dermatol 44:310–312, 2019

Sarcoid

Petrified ears JAMA Derm 152:335–336, 2016

METABOLIC DISORDERS

SYNDROMES

Acromegaly

Familial cold hypersensitivity*

ACTH isolated deficiency Intern Med 56:3263–3264, 2017

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – nodular perianal lesions, ears, lips, gingival hypertrophy, hyperpigmentation, flexion contractures of joints, osteolytic defects, stunted growth Dermatology 190:148–151, 1995; Ped Derm 11:52–60, 1994

Addison's disease – calcification/ossification of the auricular cartilage JAMA Derm 152:335–336, 2016; NEJM 364:157, 2011; Int J Derm 17:799–801, 1978; JAAD 19:1, 1988; familial petrified (calcified) ears JAAD 57:S121–122, 2007 Cutaneous calcinosis Laryngoscope 95:566–576, 1985; actinic damage, acromegaly, adrenal insufficiency, mechanical trauma, radiation therapy, diabetes mellitus, following frostbite, hypopituitarism, hypothyroidism, insect bites, chondritis, ochronosis, perichondritis, sarcoid, syphilitic perichondritis, hypertension, alkaptonuria, chondromalacia, familial cold hypersensitivity JAAD 51:799–800, 2004; JAAD 49:142–144, 2003

Keutel syndrome – unusual facies, brachytelephalangy, pulmonary stenosis Am J Med Genet 24:289–294, 1986 Primrose syndrome – enlarge calcified ears; distal muscle wasting, diabetes, deafness, basal ganglia calcification Mol Syndromol 9:70–82, 2018

TRAUMA

Diabetes mellitus – petrified ears JAMA Derm 152:335–336, 2016

Acrobatic ears B J Plast Surg 42:719–721, 1989

Gout

Cauliflower ear (boxer’s ear, wrestler’s ear) – nodular deformity with fibrosis

Hypoparathyroidism Case Rep Dermatol Med 2012:410601

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Ear Lesions Diastrophic dysplasia – cystic ear during hemorrhagic phase; calcifies J Bone Jt Surg 50A:113–118, 1968 Fibrosis due to physical trauma with resolution of hematoma Frostbite – vesicles, bullae, ischemic necrosis; calcification Radiation therapy Trauma – cauliflower ear; wrestler's ear JAMA Derm 152:335–336, 2016

VASCULAR DISORDERS Polyarteritis nodosa

EAR LESIONS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – nickel, gold, palladium, hearing aids, ear drops, occupational contact dermatitis to headphones Contact Dermatitis 42:164, 2000; benign lymphoplasia (lymphocytoma cutis) (red-brown papules and nodules) of the earlobes induced by gold earrings JAAD 27:457–458, 1992; JAAD 16:83–88, 1987; contact urticaria; allergic contact granuloma – to gold sodium thiosulfate Ped Derm 26:620–621, 2009; to palladium JAAD 55:716–720, 2006; Am J Dermatopathol 26:59–62, 2004; to titanium Contact Dermatitis 55:338–341, 2006 Antiphospholipid syndrome – ear necrosis JAMA 316:450–451, 2016 Angioedema

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CONGENITAL LESIONS Accessory tragus (accessory auricle) – ear papule – isolated, Treacher Collins syndrome (mandibulofacial dysostosis; autosomal dominant); Goldenhar syndrome ((oculo-auriculo-vertebral syndrome) – macroglossia, preauricular tags, abnormal pinnae, facial asymmetry, macrostomia, epibulbar dermoids, facial weakness, central nervous system, renal, and skeletal anomalies); frontonasal dysplasia with hair follicle nevi; leptomeningeal angiomatosis; multiple epidermal nevus-like lesions; ipsilateral alopecia J Craniofacial Surg 29:372–375, 2018; Nagers syndrome; Wolf-Hirschhorn syndrome (chromosome 4 deletion syndrome), oculocerebrocutaneous syndrome Int J Dermatol 53:1442–1446, 2014; Ped Derm 17:391–394, 2000; Townes-Brocks syndrome Am J Med Genet 18:147–152, 1984; VACTERL syndrome J Pediatr 93:270–273, 1978 Accessory lobule Congenital calcinosis cutis of the ear Cutis 75:90–91, 2005; JAAD 49:117–119, 2003 Congenital circumferential skin folds – mountain range appearance; dysmorphic features, ear abnormalities, prominent philtrum with central ridge Ped Derm 29:89–95, 2012 Congenital erosive and vesicular dermatosis with reticulate supple scarring – widespread erosions, low set ears, syndactyly Ped Derm 24:384–386, 2007; Ped Derm 22:55–59, 2005; JAAD 45:946– 948,2001; Ped Derm 15:214–218, 1998; Dermatol 194:278–280, 1997; JAAD 32:873–877, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985 Congenital hypertrichosis lanuginosa – deformities of the external ear J Genet Humaine 17:10–13, 1969

Bullous pemphigoid

Congenital postauricular swelling – cyst of first branchial cleft Ped Derm 19:246–249, 2002

Cicatricial pemphigoid – personal observation

Darwinian tubercle – personal observation

Dermatitis herpetiformis – vesicles JAAD 58:S59–60, 2008

Giant antitragi

Hyper IgE syndrome – retroauricular fissures JAAD 54:855–865, 2006; AD 140:1119–1125, 2004

Hypertrichosis of pinnae – infants of diabetic mothers Pediatrics 68:745–746, 1981

IgG4 disease – post-auricular nodules BJD 175:1056–1058, 2016 Linear IgA disease (chronic bullous disease of childhood) – perioral, eyelids, ears, scalp, perineum, vulva; annular polycyclic bullae Ped Derm 15:108–111, 1998; bullae of helices of ears Ped Derm 28:471–473, 2011 Lupus erythematosus – systemic lupus, subacute cutaneous LE, discoid lupus erythematosus NEJM 269:1155–1161, 1963; chilblain lupus BJD 98:497–506, 1978; verrucous plaque Pemphigus foliaceus Pemphigus vegetans – verrucous plaque PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAMA Derm 151:627–634, 2015 Relapsing polychondritis – edematous painful red ear (red puffy ear sign); collapsed ear Clin Exp Dermatol 43:817, 2018; NEJM 362:928, 2010; Medicine 55:193–216, 1976 Rheumatoid nodule – intact or ulcerated JAAD 8:439–457, 1983; NEJM 277:7–9, 1967 Scleroderma – pallor and telangiectasia of external auditory canal Urticaria

PREAURICULAR SINUSES (EAR PITS) Ped Derm 21:191–196, 2004  Sporadic   Familial – autosomal dominant  Branchio-oto-renal syndrome (BOR) – autosomal dominant; mutation in EYA1 gene; conductive, sensorineural, mixed hearing loss; pre-­auricular pits, structural defectso fo outer, middle or inner ear; renal anomalies, renal failure, lateral cervical fistulae, cysts, or sinuses; nasolacrimal duct stenosis or fistulae Am J Kidney Dis 37:505–509, 2001  Branchio-otic syndrome – branchial anomalies, preauricular pits, hearing loss, no renal dysplasia J Med Genet 39:71–73, 2002  Branchio-oto-ureteral syndrome – bilateral sensorineural hearing loss, preauricular pit or tag, duplication of ureters or bifid renal pelvises J Dermatol 29:157–159, 2002  Branchio-oto-costal syndrome – branchial arch anomalies, hearing loss, ear and commissural lip pits, and rib anomalies J Craniofac Genet Dev Biol 1(suppl):287–295, 1985  Branchio-oculo-facial syndrome – abnormal upper lip, malformed nose with broad nasal bridge and flattened tip, lacrimal duct obstruction, malformed ears, branchial cleft sinuses and/or linear skin lesions behind ears Ann Otol Rhinol Laryngol 100:928–932, 1991   Chromosome 4 short arm deletion syndrome

286 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1   Deafness and ear pits   Goldenhar syndrome  Hemifacial microsomia syndrome – bilateral preauricular sinuses, facial steatocystoma multiplex associated with pilar cysts, sensorineural hearing loss, facial palsy, microtia or anotia, cervical appendages containing cartilage Am J Med Genet 22:135–141, 1985  Lip pits – preauricular sinuses, conductive deafness, commissural lip pits, external ear abnormalities J Med Genet 24:609–612, 1987  Bilateral defects, male transmission – bilateral cervical branchial sinuses, bilateral preauricular sinuses, bilateral malformed auricles, bilateral hearing impairment Hum Genet 56:269–273, 1981  Tetralogy of Fallot and clinodactyly – characteristic facies, preauricular pits, fifth finger clinodactyly, tetralogy of Fallot Clin Pediatr (Phila) 27:451–454, 1988  Ectodermal dysplasia – preauricular pits, tetra-amelia, ectodermal dysplasia, hypoplastic lacrimal ducts and sacs opening toward exterior, peculiar facies, developmental retardation Ann Genet 30:101–104, 1987  Waardenburg syndrome – bilateral preauricular sinuses Acta Paediatr 86:17—172, 1997  Incomplete trisomy 22 – complex congenital heart defect, membranous anal atresia without fistula, distal limb hypoplasia, partial cutaneous syndactyly of second and third toes, left preauricular pit Urology 40:259–261, 1992  Complete trisomy 22 – primitive low-set ears, bilateral preauricular pit, broad nasal bridge, antimongoloid palpebral fissures, macroglossia, enlarged sublingual glands, cleft palate, micrognathia, clinodactyly of fifth fingers, hypoplastic fingernails, hypoplastic genitalia, short lower limbs, bilateral sandal gap, deep plantar furrows Pediatrics 108:E32, 2001 Pre-auricular tags and fistulae   Cat eye syndrome Hum Genet 57:148–158, 1981   Chromosome 4 short arm deletion syndrome   Chromosome 5 short arm deletion syndrome   Trisomy 9 Pre-auricular pits, sinuses and cysts   Cat eye syndrome Hum Genet 57:148–158, 1981   Treacher-Collins syndrome   Goldenhar syndrome  Chromosome 4 deletion syndrome Am J Dis Child 122:421–425, 1971  Melnick-Fraser syndrome (branchio-oto-renal syndrome) Ped Derm 13:507–508, 1998 Supernumerary ear

DEGENERATIVE DISORDERS Diastrophic dysplasia – cystic masses of ears Primary open-angle glaucoma – diagonal earlobe creases J R Coll Physicians Lond 26:459–460, 1992

DRUG-INDUCED

Diltiazem – photolichenoid drug eruption Iododerma – verrucous plaque Isotretinoin embryopathy – small or absent or low set ears, microphthalmia, micrognathia, deafness, limb reduction or duplication Ped Derm 29:774–776, 2012; JAAD 46:161–183, 200; systemic retinoids – increased skin fragility of ears Olanzapine – eruptive xanthomas AD 139:1045–1048, 2003 Propylthiouracil vasculitis – blue necrotic ear lesions; fever, arthralgias, and myalgias JAMA Derm 151:551–552, 2015 Thalidomide embryopathy – small malformed ears

EXOGENOUS AGENTS Acupuncture beads Argyria – silver earrings; blue macules of posterior earlobe Dermatologica 177:189–191, 1988 Chloracne – comedones and cysts of posterior aspect of ear and post-auricular crease Contact urticaria Earring – embedded stud; nodule resembling keloid; embedded foreign bodies – presenting as earlobe keloids J Derm Surg Oncol 10:902–904, 1984 Ethyl chloride – frostbite Br Med J 1:125, 1979 Fetal alcohol syndrome – railroad track abnormality with prominence of crus of helix Foreign body Hydroquinone, topical – exogenous ochronosis Levamisole-adulterated cocaine – cutaneous necrosis (livedo racemosa) associated with cocaine abuse (cocaine cut with levamisole); retiform purpura with neutropenia and vasculitis; necrosis and purpura of face, ears, nose, and cheeks, trunk; thrombotic vasculopathy with stellate livedo racemosa; perinuclear ANCA positivity Cutis 102:169–170, 175–176, 2018; Clin Inf Dis 61:1840–1849, 2015; J Drugs in Dermatol 10:1204–1207, 2011; Cutis 91:21–24, 2013; JAAD 69:135–142, 2013; Cutis 91:21–24, 2013; JAAD 65:722–725, 2011; JAAD 63:530–535, 2010; AD 146:1320–1321, 2010; Ann Int Med 152:758–759, 2010; paronychial necrosis BJD 140:948–951, 1999; ear necrosis Pediatr Nephrol 14:1057–1058, 2000; snorting, injection, smoking Clin Inf Dis 61:1840–1849, 2015  Ecchymoses, bullae, stellate lesions with red borders and necrotic center; especially on ears and cheeks   Fixed drug eruptions   Lichen planus  Ulceration   Morbilliform exanthem   Hemorrhagic bullae  Acute kidney failure J Drugs in Dermatol 10:1204–1207, 2011; Pediatr Nephrol 14:1057–1058, 2000 Mudi-chood – hyperpigmented papules with surrounding rim of scale (India) BJD 95:197–198, 1976 Titanium alloy granulomatous reaction – earlobe nodules JAAD 55:716–720, 2006

Bromoderma – verrucous plaque Corticosteroids, topical – milia on pinna Clin Exp Derm Sep2(3):285–286, 1977

INFECTIONS AND INFESTATIONS

Cyclosporine-induced folliculodystrophy – cobblestoned follicular papules JAAD 50:310–315, 2004

Abscess

Dilantin – hypertrophy of retro-auricular folds Cutis 30:207–209, 1982

Aspergillosis – ulcer of ear Ped Derm 19:439–444, 2002

Actinomycosis

Ear Lesions

287

Bacillary angiomatosis – red papules and nodules Clin Dermatol 38:160–175, 2020

polychondritis Case Rep Infect Dis 2016:7802423; histiocytoid variant of lepromatous leprosy Int J Dermatol 52:580—586, 2013

Blastomycosis-like pyoderma – verrucous plaque

Lobo's disease ((lobomycosis) keloidal blastomycosis) – Lacazia loboi; enlarged ear; cobblestoned appearance JAAD 77:197–218, 2017; JAAD 53:931–951, 2005; Cutis 46:227–234, 1990; Int J Derm 17:572–574, 1978

Borrelial lymphocytoma Clin Inf Dis 63:914–921, 2016 Candidal granuloma – verrucous plaque; ear dermatitis in chronic mucocutaneous candidiasis Ped Derm 19:415–418, 2002 Carbuncle Cellulitis Chikungunya fever – in infants, starts with hyperpigmentation of tip of nose (chik sign), ear pinnae, flexures, periorally, then generalizes to entire body; some vesiculobullous lesions JAMA Derm 156:99– 101, 2020 Chromoblastomycosis – verrucous plaque JAAD 53:931–951, 2005; AD 119:87–89, 1983; Fonsacea nubica China Mycoses 59:662– 667, 2016 Cryptococcosis – verrucous plaque Coccidioidomycosis – verrucous plaque Cutis 77:81, 111–112, 2006 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of fingers, palmar erythema, red papules of ears, red papules of antecubital fossa, perioral papulovesicles, vesicles of posterior pharynx; crusted papules of scalp, ears, and face; purpuric targetoid painful vesicular lesions of hands and feet, arthritis, fissured scrotum JAMA Derm 149:1419–1421, 2013; JAAD 69:736–741, 2013 Demodectic frost – white frost of earlobe JAMA Derm 153:356–357, 2017 Diphtheria – superficial round ulcer with overhanging edge; gray adherent membrane; later edge thickens and becomes raised and rolled; umbilicus, post-auricular, groin, finger or toe web; heals with scarring; crusts around nose and mouth with faucial diphtheria Schweiz Rundsch Med Prax 87:1188–1190, 1998; Postgrad Med J 72:619–620, 1996; Am J Epidemiol 102:179–184, 1975 Erysipelas Furuncle Herpes simplex- chronic herpes simplex – verrucous plaque; chronic herpes simplex in AIDS Herpes zoster – Ramsey-Hunt syndrome Histoplasmosis – verrucous plaque Int J Derm 30(2):104–108, 1991 HIV photosensitivity – personal observation Hot tub folliculitis – personal observation HTLV-1 infective dermatitis Am J Dermpathathol 37:944–948, 2015; BJD 150:958–965, 2004 Impetigo contagiosum – staphylococcal, streptococcal Infectious eczematoid dermatitis Insect bite NEJM 373:2070–2077, 2015 Leishmaniasis, American – chiclero ulcer J Drugs in Dermatol 13:210–215, 2014; JAAD 60:897–925, 2009; L. mexicana – may invade cartilage and destroy pinna JAAD 73:897–908, 2015; resembling lymphocytoma of earlobe BJD 157:1042–1043, 2007; L. martiniquensis – fibrotic nodules of helices of ears BJD 173:663– 670, 2015 Leprosy – lepromatous; thickened wrinkled earlobes Ped Derm 32:863–864, 2015; AD 148:1096–1097, 2012; AD 100:407–412, 1969; borderline lepromatous leprosy Clin Inf Dis 50:1015–1016, 1068–1069, 2010; megalobule – elongated hanging loose Int J Dermatol 46:600–606, 2007; type 1 leprosy reaction – papules and plaques on tragus; plaque of face JAMA Derm 149:74–78, 2013; Lucio’s phenomenon – personal observation; mimicking relapsing

Lyme borreliosis (Borrelia burgdorferi) – lymphocytoma cutis of the ear lobe; bluish-red plaque JAAD 49:363–392, 2003; JAAD 38:877–905, 1998; Infection 19:284–286, 1991; adult Clin Infect Dis 63:914–921, 2016 Molluscum contagiosum Mycobacterium avium complex – plaque of earlobe, ear, and cheek Lancet Infect Dis 9:136, 2009 Mycobacterium bovis Ann DV 143:611–615, 2016 Mycobacterium marinum Mycobacterium tuberculosis – lupus vulgaris – “turkey ear” BJD 157:816–818, 2007; – extensive destruction Cutis 15:499–509, 1975; starts as red-brown plaque, enlarges with serpiginous margin or as discoid plaques; apple-jelly nodules; myxomatous form with large tumors of the earlobes Cutis 67:311–314, 2001; Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960; giant infiltrated ear lobe (lupus vulgaris) AD 138:1607–1612, 2002; papulonecrotic tuberculid – dusky red crusted or ulcerated papules occur in crops on elbows, hands, feet, knees, legs; also ears, face, buttock, and penis Ped Derm 15:450–455, 1998; Int J Dermatol 30:487–490, 1991; Ped Derm 7:191–195, 1990multilobulated tumor of the earlobe BJD 150:370– 371, 2004; tuberculosis verrucosa cutis North American blastomycosis – verrucous plaque AD 142:795– 797, 2006 Otitis externa – swimmer’s ear; Pseudomonas aeruginosa NEJM 373:2070–2077, 2015; Clin Otolaryngol 17:150–154, 1992; Arch Environ Health 37:300–305, 1982 Otomycosis – Candida, Aspergillus Paracoccidioidomycosis – enlarged earlobe resembling leprosy Annual Meeting AAD 2000 Pediculosis – head lice with elephantiasis of the ear Acta DV (Stockh) 63:363–365, 1983 Pneumocystis carinii (jirovecii) – classified as fungus (not protozoan); red or skin colored papules or nodules in ear or external auditory canal JAAD 60:897–925, 2009; red nodular infiltrated ear; polyps within external auditory canal Am J Med 85:250–252, 1988 Protothecosis – verrucous plaque Scabies – localized crusted scabies – verrucous plaque Clin Exp Dermatol 17(5):339–341, 1992; hyperkeratotic ears, scaly abdomen and hand Cutis 94:86–88, 95, 2014 South American blastomycosis (paracoccidioidomycosis) – verrucous plaque Sporotrichosis – verrucous plaque AD 115:1229–1230, 1979 Subperichondrial abscess Am Fam Physician 75:1379–1380, 2007 Syphilis – primary chancre secondary Br J Venereol Dis 57:30–32, 1981 Tinea corporis Dermatologica 141:138–142, 1970 Tinea versicolor Trichodysplasia spinulosa – polyomavirus infection of immunocompromised host; progressive alopecia of eyebrows initially, then scalp and body hair and red follicular papules of nose, ears, forehead; leonine facies JID Symposium Proceedings 4:268–271, 1999 Warts – verrucous plaque

288 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFILTRATIVE DISEASES Amyloid – grouped papules of the auricular concha JAAD 62:1078– 1079, 2010; JAAD 18:19–25, 1988; nodular amyloidosis AD 139:1157–1159, 2003; lichen amyloid – hyperkeratotic plaques of conchal bowls BJD 161:1217–1224, 2009 Benign cephalic histiocytosis – cheeks, forehead, earlobes, neck JAAD 47:908–913, 2002; Ped Derm 11:265–267, 1994; Ped Derm 6:198–201, 1989; AD 122:1038–43, 1986; JAAD 13:383–404, 1985

Crohn’s disease – metastatic Crohn’s disease BJD 95:551–554, 1976 Cryoglobulinemia – necrotic ears BJD 143:1330–1331, 2000; type 1 cryoglobulinemia in multiple myeloma – acral cyanosis, Raynaud’s phenomenon; livedoid necrosis of arms, ears JAMA Derm 151:659– 660, 2015; type 1 cryoglobulinemia in Waldenstrom’s macroglobulinemia or myeloma Medicine (Balt) 92:61–68, 2013; Am J Med 57:775–788, 1974

Colloid milium Clin Exp Dermatol 18:347–350, 1993; BJD 125:80– 81, 1991

Gout – tophi JAMA Derm 149:245–246, 2013; Cutis 92:190–192, 2013; Cutis 48:445–451, 1991; Ann Rheum Dis 29:461–468, 1970

IgM storage papule – pink or skin colored BJD 106:217–222, 1982

Liver disease, chronic – telangiectasias of ears

Jessner’s lymphocytic infiltrate

Myxedema AD 122:85–88, 1986

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – limb contractures, sclerodermoid changes; gigantic lip fibromas, giant fibrous nodules of scalp and ears; giant nodules of frontal scalp and face; periarticular nodules of knees; gingival hypertrophy, bone deformities; mutation in gene encoding capillary morphogenesis protein 2 (ANTRX2(CMG2)) Ped Derm 23:458–464, 2006; JAAD 55:1036–143, 2006; Pediatrics 87:228–234, 1991

Ochronosis – blue discoloration of cartilage, black cerumen

Juvenile xanthogranuloma JAAD 36:355–367, 1997 Langerhans cell histiocytosis – cutaneous findings include crops of red-brown or red-yellow papules, vesicopustules, erosions, scaling, and seborrheic dermatitis-like papules, petechiae, purpura, solitary nodules, bronze pigmentation, lipid infiltration of the eyes, white plaques of the oral mucosa, onycholysis, and onychodystrophy Curr Prob Derm VI Jan/Feb 1994; Clin Exp Derm 11:183–187, 1986; JAAD 13:481–496, 1985; Head Neck 17:226–231, 1995 Lymphocytoma cutis – personal observation Scleromyxedema (lichen myxedematosus) JAAD 44:273–281, 2001; JAAD 33:37–43, 1995; JAAD 14:1–18, 1986

INFLAMMATORY DISEASES Chondrodermatitis nodularis chronicus helicis AD 146:1080–1082, 2010; Ped Derm 24:337–339, 2007; AD 68:241–255, 1953

Paroxysmal nocturnal hemoglobinuria – hemorrhagic bullae of ears; petechiae, ecchymoses, red plaques which become hemorrhagic bullae with necrosis; lesions occur on legs, abdomen, chest, nose, and ears; deficiency of enzymes – decay-accelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL) AD 138:831–836, 2002; AD 114:560–563, 1978 Peripheral symmetric gangrene – disseminated intravascular coagulation (DIC); thrombotic thrombocytopenic purpura (TTP) Porphyria - porphyria cutanea tarda – sclerodermoid changes, blisters, erosions, scarring, hyperpigmentation, hypertrichosis; congenital erythropoietic porphyria (Gunther’s disease) – mutilation of the ears Semin Liver Dis 2:154–63, 1982; erythropoietic porphyria – mutilation of ears Pretibial myxedema (thyroid acropachy) – verrucous plaque JAAD 46:723–726, 2002 Verruciform xanthoma, disseminated BJD 151:717–719, 2004; JAAD 25:330–331, 1991 Xanthomas – Alagille syndrome Ped Derm 15:199–202, 1998; normolipemic xanthomatosis – skin-colored ear nodules JAAD 51:663–664, 2004

Extrafacial granuloma faciale JAMA Derm 156:94–95, 2020

NEOPLASTIC DISEASES

Kikuchi's histiocytic necrotizing lymphadenitis – ear papule BJD 144:885–889, 2001; JAAD 36:342–346, 1997

Actinic keratosis

Lymphocytoma cutis – earlobe nodules Cancer 69:717–724, 1992; Acta DV (Stockh) 62:119–124, 1982; Cancer 24:487–502, 1969; idiopathic – ear lobe nodule JAAD 38:877–905, 1998

Adenoid cystic carcinoma (from ceruminous glands) Cancer 29:1169–1178, 1972

Pyoderma gangrenosum J Clin Gastroenterol 11:561–564, 1989 Cutaneous Rosai-Dorfman disease – multiple multilobulated nodules covering entire ear JAMA Derm 150:81–82, 2014

Adenocarcinoma Laryngoscope 87:1601–1612, 1977

Angioleiomyoma Clin Exp Dermatol 44:203–205, 2019 Angiolipoleiomyoma – skin colored or blue nodule JAAD 54:167– 171, 2006

Sarcoid – lupus pernio JAAD 16:534–540, 1987; BJD 112:315–322, 1985; massive enlargement of ear lobes (turkey ears) after ear piercing Clin Exp Dermatol 8:199–200, 1983; swelling and erythema of pinna Am J Otolaryngol 133:631–633, 2012

Angiosarcoma Am J Otol 12:54–56, 1991

Superficial vegetating pyoderma – personal observation

Basal cell carcinoma J Laryngol Otol 115:85–86, 2001

METABOLIC DISEASES Acrodermatitis enteropathica – dermatitis of ears Addison’s disease – hyperpigmentation of ear; petrified auricle Calcinosis cutis – solitary congenital calcified nodule of the ear subepidermal calcified nodule of the ear Ped Derm 34:195–196, 2017; Am J Dermatopathol 4:377–380, 1982; perforating congenital calcinosis cutis – white papule of helix Ped Derm 23:185–186, 2006; nodular calcification of Winer

Apocrine cystadenoma Arch Otolaryngol 106:13–19, 1980 Atypical fibroxanthoma Sem Cut Med Surg 21:159–165, 2002; Cutis 51:47–48, 1993; Cancer 31:1541–1552, 1973 Basaloid squamous cell carcinoma of the pinna ENT J 93:e19–21, 2014 Bowen’s disease Ceruminoma (adenoma of the ceruminous glands) – tumor within ear canal of ceruminous glands Head Neck Pathol 12:350–361, 2018Cancer 29:1169–1178, 1972 ceruminous pleomorphic adenoma Ceruminous adenocarcinoma; ceruminous adenoid cystic carcinoma; ceruminous mucoepidermoid carcinoma NEJM 373:2070– 2077, 2015;

Ear Lesions Ceruminous syringocystadenoma papilliferum Chondroma Collagenomas, eruptive JAAD 39:363–364, 1998 Combined adnexal tumor – papule of helix AD 120:231–233, 1984 Cutaneous horns Cylindromas (Spiegler’s tumor, turban tumor) – multiple nodules of ears AD 145:1277–1284, 2009; nodules around ears Arch Otolaryngol 106:13–19, 1980; Laryngoscope 87:1601–1612, 1977 Dermal melanocytosis – blue pigmentation of helix of auricle Ped Derm 27:305–306, 2010 Dermoid cyst of the auricle AD 130:913–918, 1994 Eccrine porocarcinoma – multilobulated nodule AD 136:1409–1414, 2000; J Derm Surg 25:733–735, 1999; Epidermal nevus – verrucous plaque; megalopinna Acta DV (Stockh) 61:365–367, 1981 Epidermoid cysts – of antihelix; of earlobe J Clin Diagnostic Res 8:167–168, 2014 Extramammary Paget’s disease – external auditory canal JAAD 47:S229–235, 2002 Fibroma – of earlobe Pamminerva Med 22:37–39, 1980 Granular cell schwannoma Granulocytic sarcoma NEJM 373:2070–2077, 2015 Hidradenoma papilliferum – external auditory canal J Laryngol Otol 95:843–848, 1981

small/medium-sized pleomorphic T-cell lymphoma, ear type BJD 164:456–458, 2011; HTLV-1 leukemia/lymphoma – personal observation CD8+ T-cell lymphoproliferative disease of the ear NEJM 373:2070– 2077, 2015 Lymphomatoid papulosis Arch Pediatr (Fr) 2:984–987, 1995 Malignant sweat gland tumors (malignant eccrine poroma, malignant eccrine spiradenoma, malignant hidradenoma, malignant cylindroma, eccrine carcinoma, apocrine carcinoma) Sem Cut Med Surg 21:159–165, 2002 Malignant teratoma Curr Prob Derm 14:41–70, 2002 MALT – personal observation Melanocytic nevus congenital nevus Melanoma – bright red vascular nodule of helix JAMA Derm 151:105–106, 2015; Br J Cancer 73:940–944, 1996; Arch Otolaryngol 92:106–113, 1970; lentigo maligna melanoma Merkel cell carcinoma Cutis 74:350–356, 2004; J Laryngol Otol 102:607–611, 1988; red nodule of earlobe BJD 146:671–673, 2002 Metastases J Laryngol Otol 103:653–656, 1989 Milia, including multiple eruptive milia – face, earlobe JAAD 37:353–356, 1997; Cutis 60:183–184, 1997; Clin Exp Dermatol 21:58–60, 1996 Milia en plaque – ears and ear lobe lesions Ped Derm 15:282–284, 1998 Mucoepidermoid carcinoma Laryngoscope 87:1601–1612, 1977

Hidrocystoma

Multiple myeloma – personal observation

Kaposi’s sarcoma BMJ Case Rep Sept 6, 2013; Ann Med 100:107– 114, 1984

Myoma

Keloid J Drugs Dermatol 10:468–480, 2011; JAAD 36:490–491, 1997; Lancet 335:335–336, 1990

Neurofibroma Plast Reconstr Surg 70:217–219, 1982

Keratoacanthomas – single; multiple self-healing keratoacanthomas of Ferguson-Smith – cluster around ears, nose, scalp; red nodule becomes ulcerated, resolve with crenellated scar; develop singly or in crops Cancer 5:539–550, 1952; one reported unilateral case AD 97:615–623, 1968 Familial lentiginosis – personal observation Leiomyoma Ann Diagn Pathol 41:62–68, 2019

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Neurilemmoma Laryngoscope 87:1760–1764, 1977 Nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris) BJD 67:317–319, 1955 Nevus sebaceus – verrucous plaque Osteoma Ann Diagn Pathol 41:62–68, 2019 Parotid gland carcinoma – local extension Pilomatrixoma Ped Derm 33:347–348, 2016; Derm Surg 21:245– 246, 1995

Leukemia cutis – chronic lymphocytic leukemia BJD 144:1092– 1094, 2001; chronic lymphocytic leukemia – multilobulated helices AD 147:1443–1448, 2011

Pleomorphic adenoma Laryngoscope 87:1601–1612, 1977

Lipofibroma, pedunculated JAAD 31:235–240, 1994

Pseudolymphoma – earlobe nodule BJD 171:1567–1570, 2014

Lymphoid hyperplasia NEJM 373:2070–2077, 2015

Rhabdomyosarcoma Laryngoscope 92:424–440, 1982

Lymphoma – cutaneous T-cell lymphoma presenting on auricular helix Ear Nose Throat J 79:391–394, 2000; primary cutaneous peripheral T-cell lymphoma – ear plaques BJD 164:677–679, 2011; large B-cell lymphoma – red papules along margin of helix AD 143:417–422, 2007; hydroa vacciniforme-like papulovesicular eruptions of angiocentric lymphoma associated with Epstein-Barr virus; edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 69:112–119, 2013; Ped Derm 29:96–100, 2012; AD 133:1081– 1086, 1997; angiocentric lymphoma – earlobe ulcers BJD 142:1013–1016, 2000; B-cell lymphoma – ear lobe papule Cutis 62:69–72, 1998; lymphoplasmacytoid lymphoma (B-cell lymphoma, immunocytoma) JAAD 49:1159–1162, 2003; primary cutaneous epidermotropic CD8+ T-cell lymphoma – mixture of patches, plaques, papulonodules with central ulceration, necrosis, and hemorrhage JAAD 62:300–307, 2010; primary cutaneous CD8+

Sebaceous adenoma – on pinna or in canal

Proliferating epidermoid cysts – of earlobe AD 144:547–552, 2008; J Cutan Pathol 22:394–406, 1995

Sebaceous carcinoma JAAD 48:401–408, 2003 Seborrheic keratosis Squamous cell carcinoma J Laryngol Otol 115:85–86, 2001; Clin Exp Derm 24:337, 1999; ulcer AD 123:253, 255–256, 1987; squamous cell carcinoma of the external auditory canal – ulcerated nodule with extensive destruction and purulent discharge Cancer 59:156–160, 1987 Syringocystadenoma papilliferum Arch Otolaryngol 106:13–19, 1980 Trichodiscomas – multiple agminated trichodiscomas of earlobe JAAD 49:729–730, 2003 Trichoepithelioma – external auditory meatus J Laryngol Otol 95:835–841, 1981 Trichofolliculoma – external auditory meatus J Laryngol Otol 95:623–625, 1981

290 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Verrucous carcinoma

Epidermolytic hyperkeratosis

Waldenstrom’s macroglobulinemia – multilobulated infiltration of helix NEJM 344:816, 2001; with lymphoplasmacytoid B cells – chest, earlobes, facial papules JAAD 45:S202–206, 2001

Flegel's disease (hyperkeratosis lenticularis perstans) – keratinous papules of calves; spread to concha of ears BJD 116:681–691, 1987

Xanthogranuloma Ann Diagn Pathol 41:62–68, 2019

Granuloma annulare Am J Dermatopathol 14:431–433, 1992; JAAD 3:217–230, 1980; perforating granuloma annulare BJD 147:1026– 1028, 2002

PARANEOPLASTIC DERMATOSES

Granuloma faciale, extrafacial JAMA Derm 156:94–95, 2020;

Bazex syndrome (acrokeratosis paraneoplastica) – psoriasiform dermatitis along helices NEJM 373:2161, 2015; Cutis 74:289–292, 2004; Paris Med 43:234–237, 1922; earlobe dermatitis Cutis 55:233–236, 1995

BJD 145:360–362, 2001; Dermatology 198:79–82, 1999; AD 79:42–52, 1959 Hamilton’s sign – hypertrichosis

PHOTODERMATOSES

Harlequin fetus (ichthyosis congenital fetalis) – severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis – rudimentary ears JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982

Annular elastolytic granuloma

Ichthyosis en confetti – microtia JAMA Derm 151:64–69, 2015

Dermatoheliosis

Keratosis lichenoides chronica – ear papules in childhood Clin Exp Dermatol 27:283–285, 2002

Elastotic nodules of the ears (weathering nodules) – white papules along the helix; bilateral nodules of anterior crus of antihelix or helix Cutis 98:392, 2016; AD 149:475–480, 2013; Cutis 44:452–454, 1989; JAAD 50:100, 2004; BJD 135:550–554, 1996; Cutis 44:452– 454, 1989; J Cutan Pathol 8:429–433, 1980 Hydroa vacciniforme – bullae of ears and hands AD 142:515–520, 2006; mutilation of the ear Clin Exp Dermatol 23:70–72, 1998; crusted vesicles and scars BJD 144:874–877, 2001; hydroa vacciniforme (Epstein-Barr virus-related) – red macules progress to tender papules or vesiculopapules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of cheeks, eyelids, ears, and lips AD 142:587–595, 2006 Juvenile spring eruption (variant of polymorphic light eruption) – often vesicular (lambing ears) BJD 168:1066–1072, 2013; JAAD 50:S57–60, 2004; Int J Derm 29:284–286, 1990 Juvenile spring eruption Ped Derm 36:533–534, 2019; vesicular eruption of helices, lips and cheeks due to Parvovirus B19 JAMA Derm 154:1356–1357, 2018

PRIMARY CUTANEOUS DISEASES Acne rosacea – otophyma Facial Plast Surg 14:241–253, 1998 Acne vulgaris – comedones, cysts Alopecia mucinosa Angiolymphoid hyperplasia with eosinophilia – red-brown papules and/or nodules JAAD 74:506–512, 2016; NEJM 373:2070–2077, 2015; AD 143:841–844, 2007; AD 136:837–839, 2000; JAAD 12:781–796, 1985; BJD 81:1–14, 1969; massively enlarged infiltrated ear AD 147:507–508, 2011 Atopic dermatitis – infra-auricular dermatitis and fissures NEJM 373:2070–2077, 2015 Collodion baby – eclabium; congenital erythroderma, ectropion, deformed ears, alopecia; mutation in ABCA12 BJD 166:218–221, 2012 Cutis laxa – pendulous earlobes BJD 164:215–217, 2011; JAAD 24:504–505, 1991; Cutis laxa – acquired cutis laxa of the face; sagging earlobes Ped Derm 28:421–423, 2011 Darier's disease – mimicking dermatitis J Laryngol Otol 106:725– 726, 1992; verrucous plaque Dilated pore of Winer – within external ear canal Auris Nasus Larynx 28:349–352, 2001 Epidermolysis bullosa

Lamellar ichthyosis – hypoplasia of ear cartilage Lethal acantholytic epidermolysis bullosa – universal alopecia, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010 Lichen planus, hypertrophic – verrucous plaque; lichen planus pigmentosus-inversus Low set ears – isolated phenomenon Milia en plaque – earlobes, post-auricular area Derm Surg 28:291–295, 2002; Cutis 22:67–70, 1978; Bull Soc Franc Derm Syph 14:361, 1903; of ears Ped Derm 29:504–506, 2012 Nagashima type palmoplantar keratoderma – autosomal recessive; transgradiens; acral erythema of palms and soles; hyperkeratosis of elbows and knees and ears; toenail dystrophy; mutation in SERPINB7 BJD 171:847–853, 2014; AD 144:375–379, 2008 Phylloid hypermelanosis – serpiginous hyperpigmentation with macrocephaly, frontal bossing, hypertelorism, internal strabismus, ear anomalies Ped Derm 31504–506, 2014 Pityriasis rosea Pityriasis rubra pilaris Perifollicular macular atrophy (perifollicular elastolysis) – gray-white finely wrinkled round areas of atrophy with central hair follicle; earlobes BJD 83:143–150, 1970 Phylloid hypermelanosis – cicatricial alopecia, onychodystrophy, deafness, malformed ear, mental retardation, umbilicated nipples JAAD 19:1037–1044, 1988; Rev Neurol (Paris) 95:48–54, 1956 Psoriasis Retroauricular, follicular, and keratotic plaques with multiple follicular cysts Med Cutano Ibero Lat Am 13:331–334, 1985 Seborrheic dermatitis Ulerythema ophryogenes – ear papules

SYNDROMES Aarskog syndrome – malformed ears Birth Defects 11:25–29, 1975; J Pediatr 77:856–861, 1970 Ablepharon macrostomia syndrome – absent eyelids, ectropion, abnormal ears, hypertelorism, aplasia or rudimentary nipples, dry, lax, redundant skin, macrostomia, ambiguous genitalia Hum Genet 97:532–536, 1996; Am J Med Genet 31:299–304, 1988

Ear Lesions Ablepharon with follicular ichthyosis and hairy pinnae Clin Genet 2:111–114, 1971 Acardi-Goutieres syndrome – chilblains of helices of ears; edema, erythema, ulcerations; gain of function mutations of IFIH1 BJD 173:1369–1370, 2015 Acrocephalosyndactyly – malformed ears Activated STING in Vascular and Pulmonary syndrome – autoinflammatory disease; butterfly telangiectatic facies; acral violaceous psoriasiform, papulosquamous and atrophic plaques of vasculitis of hands; nodules of face, nose, and ears; fingertip ulcers with necrosis; nail dystrophy; nasal septal perforation; interstitial lung disease with fibrosis; polyarthritis; myositis NEJM 371:507–518, 2014 Ambras syndrome – hypertrichosis of external ears Clin Genet 57:157–158, 2000 Ankyloblepharon, ectodermal dysplasia, cleft lip/palate with ectrodactyly (AEC) syndrome – diffuse erythema with fine scaling and shallow erosions; no scalp hair or eyebrows or eyelashes; ectropion and ankyloblepharon; low set ears, broad and beaked nose; downturned mouth; widely spaced teeth, nail dystrophy; ectrodactyly of right foot, choanal stenosis; erosive scalp and diaper dermatitis Ped Derm 28:15–19, 2011 Apert’s syndrome – small ears Ataxia telangiectasia – telangiectasias of bulbar conjunctivae, tip of nose, ears, antecubital and popliteal fossae, dorsal hands and feet; atrophy with mottled hypo- and hyperpigmentation, dermatomal CALMs, photosensitivity, canities, acanthosis nigricans, dermatitis; cutaneous granulomas present as papules or nodules, red plaques with atrophy or ulceration JAAD 10:431–438, 1984 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Syndrome Ident 8:6–9, 1982 Basaloid follicular hamartoma syndrome Beals-Hecht syndrome (contractural arachnodactyly) – autosomal dominant; crumpled ears, arachnodactyly with congenital joint contractures; confused with Marfan’s syndrome J Bone Joint Surg 53:987–993, 1971 Beare-Stevenson cutis gyrata syndrome – malformed ears Ped Derm 20:358–360, 2003 Beckwith-Wiedemann syndrome – diagonal linear grooves of the ear lobes, preauricular tags or pits, nevus flammeus of central forehead and upper eyelids, macroglossia, macrosomia, omphalocele or other umbilical anomalies; hypertrophy of trunk or limbs JAAD 74:231–244, 2016 Birt-Hogg-Dube syndrome – fibrofolliculomas of ears; thyroid nodules or cysts; mutation in FLCN BJD 162:527–537, 2010 Bloom’s syndrome – oversized ears JAAD 75:855–870, 2016 Borjeson-Forssman-Lehmann syndrome – large ears Am J Med Genet 19:653–664, 1984 Branchiooculofacial syndrome – autosomal dominant; congenital bilateral cervical ulcerations (bilateral ectopic thymus glands); congenital ulcerated neck mass (ectopic thymus), flattened nasal tip, pseudo-­cleft lip, posterior rotated ears, pre-auricular pit, cleft lip, microphthalmia, coloboma, nasolacrimal duct stenosis or atresia, dolichocephaly; mutation in TFAP2A (retinoic acid responsive gene) Ped Derm 29:759–761, 2012; Mol Vis 16:813–818, 2010; Arch Otolaryngol Head Neck Surg 128:714–717, 2002; pseudocleft of

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upper lip, cleft-lip-­palate, and hemangiomatous branchial cleft – atrophic neck lesions Ped Derm 29:383–384, 2012; Am J Med Genet 27:943–951, 1987 Branchio-oto-renal syndrome - autosomal dominant, chromosome 8q – abnormal pinna (small malformed ears), prehelical pits, renal anomalies, branchial cleft fistulae and/or cysts C syndrome – malformed ears Birth Defects 5:161–166, 1969 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks and arms, chondritis with progressive ear and saddle nose deformities, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, splenomegaly, protuberant abdomen JAAD 62:489–495, 2010 Carbohydrate-deficient glycoprotein syndrome – large ears; emaciated appearance; lipoatrophy over buttocks; lipoatrophic streaks extend down legs; high nasal bridge, prominent jaw, inverted nipples, fat over suprapubic area and labia majora, fat pads over buttocks; hypotonia Cardio-acro-facial syndrome (Rabenhorst syndrome) – attached earlobes, cardiac lesions, narrow face with high narrow nose Z Kinderheilk 117:109–114, 1974 Cardiofaciocutaneous syndrome – low set ears with linear earlobe creases; brittle, dark, sparse curly hair; increased numbers of melanocytic nevi; characteristic facies with thick facial appearance, broad nose, frontal bossing, ulerythema ophyrogenes, sparse eyebrows; 1–2 café au lait macules; palmoplantar keratoderma; pulmonic stenosis, hypertrophic cardiomyopathy, congenital heart defects, psychomotor delay, failure to thrive; RASopathy (BRAF, MAP2K1, MAP2K2, KRAS mutations) BJD 164:521–529, 2011 Carney complex – cutaneous myxomas (superficial angiomyxoma) of the ears (papules) Cutis 62:275–280, 1998; JAAD 43:377–379, 2000; J Surg Pathol 18:274–280, 1994; lentigines of ears JAAD 46:161–183, 2002 Cat eye syndrome – preauricular tags or pits Acta Pediatr Scand 63:623–626, 1974 Char syndrome – short philtrum, patulous lips, ptosis, low-set pinnae Birth Defects 14(6B):303–305, 1978 CHARGE syndrome – coloboma, heart disease, choanal atresia, somatic and mental retardation, genital hypoplasia, low-set malformed small ears JAAD 46:161–183, 2002; Perspect Pediatr Pathol 2:173–206, 1975 Cleft lip and palate, abnormal ears, congenital heart defect, skeletal abnormalities Acta Paediatr Scand 70:767–769, 1981 Cleft lip and palate, pili torti, malformed ears, partial syndactyly of fingers and toes, mental retardation J Med Genet 24:291–293, 1987 Cockayne's syndrome – autosomal recessive; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects, demyelination J Med Genet 18:288–293, 1981 Coffin-Lowry syndrome – prominent ears Hum Genet 36:271–276, 1977 Cohen syndrome – large ears J Med Genet 17:430–432, 1980 Congenital hemidysplasia, ichthyosiform erythroderma, and limb defects (CHILD syndrome) – hyperkeratotic papules of ears, dorsal foot Ped Derm 30:250–252, 2013

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Costello syndrome – low set protuberant ears with thick earlobes, warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi Ped Derm 30:665–673, 2013; Am J Med Genet 117:42–48, 2003; Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977 Cowden’s syndrome – skin-colored papules AD 146:337–342, 2010 Cri du chat syndrome (chromosome 5, short arm deletion syndrome) – premature greying of the hair, pre-auricular skin tag with low-set malformed ears J Pediatr 102:528–533, 1983 Crouzon’s syndrome – low set ears Crouzon’s syndrome with acanthosis nigricans (CAN) – onset of acanthosis nigricans during childhood, melanocytic nevi, craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hypertelorism, anti-Mongoloid slant, posteriorly placed ears, hydrocephalus; mutation in FGFR3 JAMA Derm 149:737–741, 2013; Ped Derm 27:43–47, 2010; Am J Med Genet 84:74, 1999 Cryptophthalmos syndrome (Fraser syndrome) – malformed ears Am J Med Genet 31:159–168, 1988 Deformed ear and genital lentigines – personal observation Del (18p) syndrome – large ears Eur J Pediatr 123:59–66, 1976 Delleman syndrome (oculocerebrocutaneous syndrome – multiple accessory tragi with aplasia cutis congenital AD 147:345–350, 2010 Diastrophic dysplasia – cystic ear during hemorrhagic phase; calcifies J Bone Jt Surg 50A:113–118, 1968 DiGeorge sequence – small and pointed posteriorly angulated ears JAAD 46:161–183, 2002; J Pediatr 94:883–890, 1979 Deafness, pre-auricular sinus, external ear anomaly, and commissural lip pit syndrome – autosomal dominant; pinna dysplasia, mixed or conductive hearing loss Cutis 88:275–278–280, 2012; Laryngoscope 76:1277–1288, 1966; Br Med J ii:1354–1356, 1955 Deletion of short arm of chromosome 4 (4p- syndrome) – ACC of scalp with hypertelorism, beaked or broad nose, microcephaly, low set ears, pre-auricular tags or pits, mental retardation Am J Dis Child 122:421–425, 1971 Disorganization syndrome – filiform worm-like projections, syndactyly, popliteal pterygium, polydactyly, cleft lip/palate; ear abnormalities Ped Derm 24:90–92, 2007; J Med Genet 26:417–420, 1989 Down’s syndrome – low-set, small ears JAAD 46:161–183, 2002 Duane retraction syndrome – small ears Dubowitz’s syndrome – severe eczema, sparse hair, sparse arched eyebrows, dysplastic ear pinnae Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959–964, 1993 Dup (11q) syndrome – preauricular pits or tags Clin Genet 25:295–299, 1984 Ehlers-Danlos syndrome – unusual appearance of ears; EDS type IV – lobeless ears; acrogeric skin type; prominent eyes; dry wrinkled pigmented skin of arms and legs; pinched nose; thin translucent skin with bruising; joint hyperextensibility; abnormal type III collagen and defect in type III collagen synthesis; spontaneous vascular rupture; BJD 163:704–710, 2010; JAAD 55:S41–45, 2006 Familial chilblain lupus – paronychia, acral erythema, acral papules, necrotic ulcers, facial ulcers, mutilation of fingers, ear lesions; mutation of exonuclease III domain of 3’ repair exonuclease 1 (TREX1) JAMA Derm 151:426–431, 2015

Familial multiple discoid fibromas (Birt-Hogg-Dube look-alike) – red papules of cheeks, around nose, helices and posterior ears, skin-colored papules with overlying telangiectasias; white papules of face and ears BJD 169:177–180, 2013; JAAD 66:259–263, 2012 Farber's disease (disseminated lipogranulomatosis) – lysosomal acid ceramidase deficiency (N-acylsphingosine amidohydrolase) (chromosome 8p22-21.2); red papules and nodules of joints and tendons of hands and feet (proximal and distal interphalangeal joints, wrist, elbow, knees, ankles, metatarsals); deforming arthritis; papules, plaques, and nodules of ears, back of scalp and trunk; and progressive hoarseness; rarely nodules seen in conjunctivae, nostrils, ears, mouth; heart, liver, spleen, lung; progressive psychomotor retardation Ped Derm 26:44–46, 2009; Eur J Ped 157:515–516, 1998; AD 130:1350–1354, 1994; Am J Dis Child 84:449–500, 1952 Fetal alcohol syndrome – malformed ears Drug Alcohol Depend 14:1–10, 1984 Fetal hydantoin syndrome – malformed ears Am J Dis Child 127:758, 1974 FG syndrome – unusual facies, mental retardation, congenital hypotonia, imperforate anus; small ears Am J Med Genet 12:147– 154, 1982 Fibroblastic rheumatism – symmetrical polyarthritis, nodules over joints and on palms, elbows, knees, ears, neck, Raynaud’s phenomenon, sclerodactyly; skin lesions resolve spontaneously AD 139:657–662, 2003; AD 131:710–712, 1995; Clin Exp Dermatol 19:268–270, 1994; Rev Rheum Ed Fr 47:345–351, 1980 Fibrodysplasia ossificans progressiva – heterotopic bone formation within soft tissues; malformed external ear; soft tissue swellings, multiple neonatal scalp nodules associated with malformation of the great toes (hallux valgus); hypoplastic great toes; development of tumors is cranial to caudal, dorsal to ventral and proximal to distal; ossification after infections or trauma; scalp nodules large, firm, and immobile; death from pulmonary disease; mutation in ACVR1 gene JAAD 64:97–101, 2011 Finlay-Marks syndrome (scalp-ear-nipple syndrome) – nipple or breast hypoplasia or aplasia, aplasia cutis congenita of scalp, abnormal ears and teeth, nail dystrophy, syndactyly, reduced apocrine secretion First and second branchial arch cleft syndromes – small ears Fragile X syndrome – large ears J Ment Defic Res 27:211–226, 1983 Francois syndrome (dermochondrocorneal dystrophy) – knuckle pads; nodules on hands, nose, and ears Ann DV 104:475–478, 1977; AD 124:424–428, 1988 Goldenhar syndrome (oculo-auriculo-vertebral syndrome) – macroglossia, preauricular tags, small abnormal pinnae, low-set ears, facial asymmetry, macrostomia, epibulbar dermoids, facial weakness, central nervous system, renal, and skeletal anomalies, Ped Derm 24:657–658, 2007; JAAD 50:S11–13, 2004; Am J Med Genet 26:361–375, 1987 Goltz’s syndrome – protruding ears, mid-facial hypoplasia, pointed chin, lower limb hypoplasia, blaschko-esque atrophy, red and hypopigmented blaschko streaks, painful exophytic granulation tissue, giant cell tumor of bone (large subcutaneous nodule) BJD 160:1103–1109, 2009 Greig cephalopolysyndactyly – malformed ears Clin Genet 24:257–265, 1983 Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and

Ear Lesions penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, bilateral single palmar crease, hirsutism, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006 Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa (floppy ears), corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

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Lacrimo-auriculo-dento-digital (LADD) syndrome – cup-shaped ears, hearing loss, nasolacrimal duct obstruction, hypodontia, enamel dysplasia, digital malformations Eur J Pediatr 146:536–537, 1987; J Med Genet 24:94–95, 1987; J Pediatr 83:438–444, 1973 Langer-Gideon syndrome (trichorhinophalangeal syndrome, type II) – large ears Am J Med Genet 19:113–119, 1984 LEOPARD (Moynahan’s) syndrome – CALMs, granular cell myoblastomas, steatocystoma multiplex, small penis, hyperelastic skin, low set ears, short webbed neck, short stature, syndactyly JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; J Dermatol 25:341–343, 1998; Am J Med 60:447–456, 1976; AD 107:259–261, 1973

Hunter syndrome(mucopolysaccharidosis type II) – accumulation of glycosaminoglycans; X-linked recessive; iduronate 2-sulfatase deficiency; recurrent otitis media, respiratory infections, hepatosplenomegaly, hernias, cardiomyopathy Ped Derm 33:594–601, 2016

Leprechaunism (Donohue syndrome) – large ears Ann Genet 30:221–227, 1987

Hutchinson-Gilford progeria syndrome – mountain range rippling of skin; sclerodermoid changes; facies – mid-frontal bossing, protruding ears with small or absent lobes, prominent eyes, glyphic nose (broad, mildly concave nasal ridge), mild micrognathia, vertical midline groove of chin, thin lips JAMA Derm 150:197–198, 2014; BJD 163:1102–1115, 2010; AD 144:1351–1359, 2008; BJD 156:1308–1314, 2007

Mandibulofacial dysostosis, microtia, talipes, agenesis of the patellae Birth Defects 11:39–50, 1975

Hypertelorism-microtia-clefting syndrome (Bixler syndrome) J Med Genet 19:387–388, 1982

MC/MR syndrome with multiple circumferential skin creases – multiple congenital anomalies including high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals, posteriorly angulated ears, short stature, pectus excavatum, inguinal and umbilical hernias, scoliosis, hypoplastic scrotum, long fingers, overlapping toes, severe psychomotor retardation with hypotonia; resembles Michelin tire baby syndrome Am J Med Genet 62:23–25, 1996

Incontinentia pigmenti – ear anomalies JAAD 47:169–187, 2002 Johnson-McMillin syndrome – autosomal dominant, facial nerve palsy, hearing loss, hyposmia, hypogonadism, microtia, alopecia Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – nodular perianal lesions, ears, lips, gingival hypertrophy, hyperpigmentation, flexion contractures of joints, osteolytic defects, stunted growth Ped Derm 18:400–402, 2001; Dermatology 190:148–151, 1995; Ped Derm 11:52–60, 1994; ear nodules Int J Paediatr Dent 6:39–43, 1996 Kabuki makeup syndrome – short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly (short 5th finger), clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental r­ etardation with microcephaly; preauricular dimple/fistula; mutation in MLL2 Ped Derm 30:253– 255, 2013; Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170– 173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849– 850, 1984; J Pediatr 99:565–569, 570–573, 1981 KID syndrome – keratosis, ichthyosis, deafness syndrome – fixed orange, symmetrical hyperkeratotic plaques of scalp, ears, and face with perioral rugae; aged or leonine facies; erythrokeratoderma-like; later hyperkeratotic nodules develop Ped Derm 17:115–117, 2000; Ped Derm 13:105–113, 1996 Laband syndrome (hereditary gingival fibromatosis) – soft, large floppy ears; bulbous soft nose, gingival fibromatosis; absent nails; atrophic distal phalanges, hyperextensible joints, hepatosplenomegaly, hypertrichosis, mental retardation Ped Derm 10:263–266, 1993; J Otol Pathol Med 19:385–387, 1990; Oral Surg Oral Med Oral Pathol 17:339–351, 1964

Lumpy scalp syndrome – autosomal dominant; irregular scalp nodules, deformed pinnae, rudimentary nipples Clin Exp Dermatol 15:240, 1989; BJD 99:423–430, 1978

MAUIE syndrome – micropinna, alopecia, ichthyosis, and ectropion JAAD 37:1000–1002, 1997 Maxillofacial dysostosis – minor ear abnormalities J Med Genet 14:355–358, 1977; X-linked Am J Med Genet 21:137–142, 1985

Melnick-Needles syndrome – large ears J Pediatr Orthoped 3:387–391, 1983 MEND – X-linked recessive; hypomorphic mutation of emopamil-­ binding protein; diffuse mild ichthyosis; telecanthus, prominent nasal bridge, low set ears, micrognathia, cleft palate large anterior fontanelle, polydactyly, 2–3 syndactyly, kyphosis, Dandy-Walker malformation, cerebellar hypoplasia, corpus callosal hypoplasia, hydrocephalus, hypotonia, developmental delay, seizures; bilateral cataracts, glaucoma, hypertelorism; cardiac valvular and septal defects, hypoplastic aortic arch; renal malformation, cryptorchidism, hypospadias BJD 166:1309–1313, 2012 Microphthalmia with linear skin defects (MIDAS syndrome) (MLS syndrome, Xp deletion syndrome, Xp 22.3 microdeletion syndrome) – Xp22.3 deletion – X-linked dominant; linear jagged skin defects of scalp, face, neck, and occasionally upper trunk, Blaschkoesque depressed patches of face, pre-auricular ear pit, severe short stature, congenital heart defects, agenesis of the corpus callosum, ambiguous genitalia, nail dystrophy Ped Derm 25:548–552, 2008; Ped Derm 20:153–157, 2003 Michelin tire baby syndrome – either nevus lipomatosis or diffuse smooth muscle hamartoma; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques; low set ears with thickened helix and anti-helix; wide nasal bridge; histologically increased periadnexal fat and subcutaneous fat and smooth muscle hamartomas; mental retardation, tendinous hyperlaxity, seizures, mastocytosis, complex malformations syndrome (bilateral calcaneovalgus deformity, cleft palate, inguinal hernia, hip deformity, clefting of lateral mouth

294

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

commissures, shawl scrotum, absent foreskin JAAD 63:1110–1111, 2010; Ped Derm 27:79–81, 2010; Ped Derm 24:628–231, 2007; Ped Derm 22:245–249, 2005; Ped Derm 20:150–152, 2003; BJD 129:60–68,1993; JAAD 28:364–370, 1993; Ped Derm 6:329–331, 1989; Am J Med Genet 28:225–226, 1987; AD 115:978–979, 1979; diffuse lipomatous hypertrophy AD 100:320–323, 1969; generalized muscular nevus Ann DV 107:923–927, 1980 Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation (nevus depigmentosus); small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Mohr’s orofaciodigital syndrome – small ears Multicentric reticulohistiocytosis – ear nodules AD 140:919–921, 2004; Clin Rheumatol 15:62–66, 1996 Nager syndrome (preaxial acrofacial dysostosis) – low set ears Birth Defects 10:109–115, 1974 Neu-Laxova syndrome – large low set ears; mild scaling to harlequin ichthyosis appearance; ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema and mildly edematous feet and hands, absent nails; microcephaly, intrauterine growth retardation, limb contractures, sloping forehead, short neck; small genitalia, eyelid and lip closures, syndactyly, cleft lip and palate, micrognathia; autosomal recessive; uniformly fatal Ped Derm 20:25–27,78–80, 2003; Curr Prob Derm 14:71–116, 2002; Clin Dysmorphol 6:323––328, 1997; Am J Med Genet 35:55–59, 1990 Neurofibromatosis type II – angiofibromas (pink-red papules) grouped on the ear AD 134:760–761, 1998 Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, growth retardation, epicanthal folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of face, café au lait macules, vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair 3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000 Noonan's syndrome – webbed neck, short stature, malformed ears, nevi, keloids, transient lymphedema, ulerythema ophyrogenes, keratosis follicularis spinulosa decalvans JAAD 46:161–183, 2002; J Med Genet 24:9–13, 1987 Opitz BBB/G compound syndrome (oculo-genito-laryngeal syndrome) – malformed ears Am J Med Genet 28:303–309, 1987 Oto-onycho-peroneal syndrome (Pfeiffer’s syndrome) – crumpled pinnae, aplasia of the nails and fibulae Eur J Paediatr 138:137–320, 1982 Pallister-Killian (Killian-Teschler-Nicola syndrome) syndrome – short neck; Blaschko hyperpigmentation, streaks of hypo- and hyperpigmentation, mental retardation, coarse facies with prominent forehead with abnormally high anterior hairline, sparse temporal hair and sparse anterior scalp hair, hypertelorism, short nose with anteverted nostrils, flat nasal bridge, flat occiput, chubby cheeks, sparse eyelashes, long philtrum with thin upper lip, horizontal palpebral fissure, large low set ears with thick lobules, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i(12p) (tetrasomy 12p); tissue mosaicism; pigmentary

mosaicism and localized alopecia Ped Derm 24:426–428, 2007; Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005; Ped Derm 17:151–153, 2000; J Clin Dysmorphol 1:2–3, 1983 Palmoplantar keratoderma, large ears, sparse hypopigmented scalp hair, frontal bossing Ped Derm 19:224–228, 2002 Patau’s syndrome (non-mosaic trisomy 13) – parieto-occipital scalp defects, cleft lip/palate, abnormal helices, low set ears, loose skin of posterior neck, simian crease of hand, hyperconvex narrow nails, polydactyly, microcephaly, microphthalmia, severe central nervous system anomalies, congenital heart defects, holoprosencephaly; death in first year Am J Med Genet 143A:1739–1748, 2007; Ped Derm 22:270–275, 2005 PHACES syndrome Post-axial acrofacial dysostosis – small malformed ears J Pediatr 95:970–975, 1979 Potter sequence (oligohydramnios syndrome) – malformed ears Syndromes of the Head and Neck; 1990, p. 4–11. PTEN-hamartoma-tumor syndrome – grossly enlarged hand; recurrent arteriovenous malformations of hand and forearm; macrocephaly, frontal bossing, café au lait macules, congenital nevi, low set ears, downward slanting eyebrows and palpebral fissures Ped Derm 28:466–467, 2011 Restrictive dermopathy – autosomal recessive, dysplastic low set ears; erythroderma at birth, with extensive erosions and contractures; taut shiny skin; fetal akinesia, multiple joint contractures, dysmorphic facies with fixed open mouth, hypertelorism, pulmonary hypoplasia, bone deformities; uniformly fatal AD 138:831–836, 2002; Ped Derm 19:67–72, 2002; Ped Derm 16:151–153, 1999; AD 134:577–579, 1998; AD 128:228–231, 1992 Reticulolinear aplasia cutis congenita of the face and neck – Xp deletion syndrome, MIDAS (microphthalmia, dermal aplasia, sclerocornea), MLS (microphthalmia and linear skin defects), and Gazali-Temple syndrome; lethal in males; low-set ears; residual facial scarring in females, short stature, organ malformations BJD 138:1046–1052, 1998 Robert's syndrome – hypomelia-hypotrichosis-facial hemangioma (pseudothalidomide) syndrome – hypoplastic ear lobules, mid forehead and midfacial port wine stain, cleft lip and/or palate, sparse silvery blonde hair, limb reduction defects, and marked growth retardation Clin Genet 5:1–16, 1974 Robinow syndrome – overfolded helix Eur J Pediatr 151:586–589, 1992 Rosai-Dorfman disease Semin Diagn Pathol 7:19–73, 1990 Rubinstein-Taybi syndrome – mental deficiency, small head, broad thumbs and great toes, beaked nose, malformed low-set ears, capillary nevus of forehead, hypertrichosis of back and eyebrows, keloids, cardiac defects Cutis 57:346–348, 1996; Am J Dis Child 105:588–608, 1963 Sakati syndrome – patchy alopecia with atrophic skin above ears, submental linear scars, acrocephalopolysyndactyly, short limbs, congenital heart disease, abnormally shaped low-set ears, ear tag, short neck with low hairline J Pediatr 79:104–109, 1971 SAVI – (STING (stimulator of interferon genes)-associated vasculopathy) – progressive digital necrosis, swelling of fingers, amputation of several digits, violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of arms and legs JAAD 74:186–189, 2016 Say syndrome – large ears, short stature, cleft palate, microcephaly Am J Med Genet 45:358–360, 1993

Ear Lesions

295

Scalp-ear-nipple syndrome – autosomal dominant; aplasia cutis congenita of the scalp, irregularly shaped pinna, hypoplastic nipple, widely spaced teeth, partial syndactyly Am J Med Genet 50:247– 250, 1994

Tuberous sclerosis – giant angiofibromas JAAD 67:1319–1326, 2012

Seckel’s syndrome – abnormal teeth, short stature, hypopigmented papules and macules, small deformed ears lacking lobules, syndactyly, clinodactyly Ped Derm 24:53–56, 2007;

Velocardiofacial syndrome – malformed ears J Craniofac Genet Dev Biol 4:39–46, 1984

Eur J Pediatr 137:237–242, 1981 Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes, congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321–327, 1996 Singleton-Merten syndrome – ulcerated chilblains, loss of secondary dentition, broadened phalanges, acral osteolysis, aortic arch and valvular calcification; chilblains of helices of ears; edema, erythema, ulcerations; gain of function mutations of IFIH1 BJD 173:1369–1370, 2015 Steatocystoma multiplex Townes-Brocks syndrome – autosomal dominant; triad of imperforate anus, lop ears associated with sensorineural and/or conductive hearing loss, preauricular tags, and thumb malformations (triphalangeal thumbs, duplication of thumb, or hypoplasia of thumb; renal failure, congenital heart disease, flat feet, genitourinary malformations; SALL1 mutation Gene Reviews (Internet). Seattle (WA), Jan 24, 2007; Dysmorphol Clin Genet 2:104–108, 1988 Treacher-Collins syndrome (mandibulofacial dysostosis) – partial or total alopecia of lower eyelashes, scarring alopecia, characteristic facies, small malformed pinnae, extension of scalp hair onto cheeks; blind fistulae between ear and angle of mouth Ped Derm 23:511– 513, 2006; Am J Dis Child 113:405–410, 1967 Trichorhinophalangeal syndrome type I – autosomal dominant; receding frontotemporal hairline with high bossed for head; facial pallor, pear-shaped nose, long philtrum, thin upper lip, receding chin, tubercle of normal skin below the lower lip, distension and deviation with fusiform swelling of the PIP joints; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, eyebrows sparse laterally, dense medially, short stature; mutation in zinc finger nuclear transcription factor BJD 157:1021–1024, 2007; AD 137:1429–1434, 2001; JAAD 31:331–336, 1994; Hum Genet 74:188–189, 1986; – large ears Cutis 89:56,73–74, 2012; BJD 95(Suppl 14):39–41, 1976 Trichorhinophalangeal syndrome type II (Langer-Giedion syndrome) – microcephaly with mental retardation, deep set eyes, exotropia, long nose with bulbous tip, broad nasal bridge, thick ala nasi, high palate, crowded teeth, micrognathia, long neck, short metacarpals, thin nails, small feet with brachydactyly, vaginal stenosis, short stature, thin sparse hair, long face, prominent ears, madarosis, cartilaginous exostoses, foot deformities, joint laxity; EXT gene BJD 171:1581–1583, 2014; BJD 157:1021–1024, 2007 Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – protruding ears, hypoplastic ears, pre-auricular pits, cleft ear lobes, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation Ped Derm 14:441–445, 1997; JAAD 44:891–920, 2001 Trisomy 18 – posteriorly rotated low-set ears, flat occiput, higharched palate, flexed hands and elbows, psychomotor retardation Clin Genet 22:327–330, 1982 Trisomy 22 syndrome – preauricular tags or pits Birth Defects 11:241–245, 1975

Turner’s syndrome – macrotia (enlarged ears); unusual shape and rotation of ears, low set ears JAAD 50:767–776, 2004

Vogt-Koyanagi-Harada syndrome – hearing aid – personal observation Weaver syndrome – large ears Am J Dis Child 138:1113–1115, 1984 Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – generalized lipoatrophy, macrocephaly, premature aging, wide open sutures, hypoplasia of facial bones, low set ears, beak shaped nose, neonatal teeth, slender limbs, large hands and feet with long fingers, large penis J Med Genet 34:433–437, 1997 Wisconsin syndrome – small malformed ears Syndromes of the Head and Neck, 1990; p. 561 Wolf-Hirschhorn syndrome (del (4p) syndrome) – preauricular tags or pits Clin Genet 10:104–112, 1976 Woodhouse-Sakati syndrome – autosomal recessive; triangular shaped face with prominent forehead, large low set ears, dystonia, hypotrichosis, with sparse eyebrows and eyelashes; alopecia, hypogonadism, diabetes mellitus, mental retardation, sensorineural deafness, extrapyramidal signs, low insulin-like growth factor 1; must be differentiated from congenital hypotrichosis; mutation in C2orf37 Ped Derm 31:83–87, 2014; Am J Med Genet 143:149–160, 2007; J Med Genet 20:216–219, 1983 XYY syndrome – large ears Syndromes of the Head and Neck, 1990; p. 61–62 Yunis-Varon syndrome – dysplastic clavicles, sparse hair, digital anomalies; malformed ears J Med Genet 26:55–58, 1989 Zimmermann-Laband syndrome – autosomal dominant; dysplastic/ absent nails, large ears and nose, hepatosplenomegaly, short terminal phalanges, hyperextensible metacarpophalangeal joints Ped Derm 18:534–536, 2001

TRAUMA Acanthoma fissuratum AD 94:621–622, 1965 Altitude injury – petechiae and hemorrhagic bullae of external auditory canal in pilots descending from high altitudes Laryngoscope 56:225–236, 1946 Bruising – athletics, child abuse (tin ear syndrome) Pediatrics 80:618–622, 1987 Cauliflower ear (boxer’s ear) – child abuse Ped Derm 29:226–227, 2012 Chilblains – with necrosis on fingers, toes, nose, and ears in patients with monocytic leukemia AD 121:1048, 1052, 1985; necrobiotic pernio Australas J Dermatol 30:29–31, 1989 Child abuse Clin Otolaryngol 42:783–804, 2017 Chondrodermatitis nodularis chronicus helicis (Winkle’s nodule) – papule of helix or antihelix; nodule JAAD 76:1103–1108, 2017; Dermatologica 163:376–384, 1981; JAAD 2:148–154, 1980 Earlobe ptosis – drooping of earlobe due to pulling JAMA Derm 130:673–674, 2014 Frostbite Habit helices – callosities on rim of auricle with underlying perichondritis in nuns AD 87:735, 1963 Keloid

296 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Othematoma – hematoma of auricle Am Fam Physician 75:1379– 1380, 2007 Pressure necrosis Prosthetic ear Pseudocyst of the auricle Cutis 77:102–104, 2006; BJD 122:699– 704, 1990; AD 125:528–530, 1989 Radiation dermatitis – acute or chronic Wrestler’s ear

VASCULAR DISEASES Acrocyanosis – blue ears JAAD S207–208, 2001 Acute hemorrhagic edema of infancy – purpura in cockade pattern of face, cheeks, eyelids, and ears; may form reticulate pattern; edema of penis and scrotum JAAD 59:684–695, 2008; JAAD 23:347–350, 1990; necrotic lesions of the ears, urticarial lesions; oral petechiae JAAD 23:347–350, 1990; Ann Pediatr 22:599–606, 1975; edema of limbs and face Cutis 68:127–129, 2001 Arteriovenous malformation – grossly enlarged ear JAAD 72:879– 889, 2015 Angiolymphoid hyperplasia with eosinophilia An Bras Dermatol 92:392–394, 2012 Arteriovenous malformation of the external ear Bras J Otorhinolaryngol 83:683–690, 2017 Atherosclerosis – diagonal earlobe crease (Frank’s sign) NEJM 289:327–328, 1973 Epithelioid hemangioma JAAD 49:113–116, 2003 Erythema elevatum diutinum Granulomatosis with polyangiitis – suppurative otitis Laryngoscope 92:713–717, 1982; destruction of ear Hemangiomas Ped Derm 29:154–159, 2012; J Pediatr Surg 35:420–423, 2000 Kaposiform hemangioendothelioma – red to purple plaque JAAD 52:616–622, 2005 Lymphangioma Plast Reconstr Surg 66:509–527, 1980 Lymphedema – recurrent elephantiasis nostras Cutis 29:441–444, 1982 Lymphostasis verrucosa cutis – verrucous plaque Peripheral symmetric gangrene (DIC) Port wine stain – enlarged ear JAMA Derm 150:1336–1340, 2014 Pyogenic granuloma NEJM 373:2070–2077, 2015 Spindle cell hemangioendotheliomas – papules Cutis 62:23–26, 1998 Vasculitis Venous lakes

 ARS, RED, WITH OR WITHOUT E NODULES

repair exonuclease 1 (TREX1;AGS1); mutation in sterile alpha motif domain and HD domain-containing protein1 (SAMHD1;AGS5); mutation in 3 genes encoding for components of ribonuclease subunit A endonuclease complex (AGS2-4); mutation in gene for RNA-specific adenosine deaminase 1 (AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1 (AGS7); chilblain-like lesions; acrocyanosis; red periungual lesions; red earlobes; livedo reticularis, blueberry muffin baby; congenital encephalopathy with developmental delay; ­microcephaly; narrow facial features; seizures, spasticity, dystonic posturing Ped Derm 33:602–614, 2016 Allergic contact dermatitis – hair care products, jewelry, ear appliances, hairpins, cosmetics, topical medicines (neomycin), nail polish Bullous pemphigoid Dermatomyositis Graft vs host reaction, acute JAAD 38:369–392, 1998; AD 134:602– 612, 1998; AD 127:1673, 1991; in children, red macules or folliculocentric papules of face, ears, palms and soles, periungual areas, upper back, and neck AD 143:67–71, 2007 Hyper IgE syndrome – post-auricular fissuring JAAD 54:855–865, 2006 Lupus erythematosus – systemic lupus erythematosus JAAD 65:54–64, 2011; Lupus 9:301–303, 2000; Clin Exp Rheum 5:349–353, 1987; auricular chondritis with red ear Clin Exp Rheumatol 5:349–353, 1987; chilblain lupus BJD 98:497–506, 1978; perforation of pinna Cutis 32:554–557, 1983; neuropsychiatric lupus 9:301–303, 2000; discoid lupus erythematosus NEJM 269:1155–1161, 1963; neonatal lupus erythematosus, subacute cutaneous lupus erythematosus – personal observation Pemphigus foliaceus/erythematosus Relapsing polychondritis Cutis 103:237–240, 2019; NEJM 378:1715, 2018; NEJM 362:928, 2010; AD 143:89–90, 2007; Medicine 55:193––216, 1976; in children Ped Derm 19:60–63, 2002; with meningoencephalitis Cutis 99:43–46, 2017 SAVI – STING-associated vasculopathy with onset in infancy syndrome – autosomal dominant; gain of function mutation in transmembrane protein 173 (STING) leading to chronic activation of Type I interferon pathway; violaceous scaling plaques of fingers, toes, nose, ears, cheeks; red ears which ulcerate with necrosis; nail loss, nail dystrophy, nasal septal perforation, severe interstitial lung disease Ped Derm 33:602–614, 2016; NEJM 371:507–516, 2014 Urticaria

DRUG Acral dysesthesia syndrome – cytarabine Eur J Cancer 26:649– 650, 1990 Chemotherapy- induced neutrophilic eccrine hidradenitis – personal observation Cocaine/levamisole vasculopathy; vasculitis Fixed drug eruption Hydantoin (Dilantin) hypersensitivity reaction

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Pegfilgastrim – Sweet’s syndrome due to pegfilgrastim (pegylated G-CSF) JAAD 52:901–905, 2005

Aicardi-Goutieres syndrome (interferonopathy) – autosomal recessive; neurodegenerative disease; mutation in three-prime

Piroxicam photoallergic drug reaction Sorafenib erythema – personal observation

Ears, Red, with or Without Nodules 297

EXOGENOUS AGENTS Benign lymphoplasia induced by gold earrings – violaceous earlobe JAAD 16:83–88, 1987

Pneumocystis carinii – red nodular infiltrated ear; polyps within external auditory canal Am J Med 85:250–252, 1988

Irritant contact dermatitis

Pseudomonas chondritis – secondary to ear piercing Ann Plast Surg 24:279–282, 1990; pseudomonas perichondritis Br J Clin Pract 44:512–513, 1990

Photodermatitis – musk ambrette JAAD 21:880–884, 1989

Scabies

INFECTIONS AND INFESTATIONS Borrelia lymphocytoma Ped Derm 29:765–766, 2012 Chikungunya fever – exanthema with red ears JAMA Derm 151:257–258, 2015; red swollen ears NEJM 372:1231–1239, 2015 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of fingers, palmar erythema, red papules of ears, red papules of antecubital fossa, perioral papulovesicles, vesicles of posterior pharynx JAAD 69:736–741, 2013 Dengue fever – exanthema with red ears JAMA Derm 151:257–258, 2015

Sporotrichosis – red ear with nodules and hyperkeratosis AD 143:1441–1446, 2007 Staphylococcal cellulitis – due to ear piercing Syphilis – secondary Tinea – tinea faciei; tinea incognito J Dermatol 22:706–707, 1995; mimicking chondritis Cutis 23:638–639, 1979 Vaccinia – laboratory acquired vaccinia virus infection; painful inflamed ear and periorbital region; MMWR 58:797–800, 2009

INFILTRATIVE DISEASES

Herpes zoster (herpes zoster oticus) – Ramsey-Hunt syndrome Otolaryngol Head Neck Surg 95:292–297, 1986

Langerhans cell histiocytosis – seborrheic dermatitis-like papules, crops of red-brown or red-yellow papules, vesicopustules, erosions, scaling, and petechiae, purpura, solitary nodules, bronze pigmentation, lipid infiltration of the eyes, white plaques of the oral mucosa, onycholysis, and onychodystrophy Head Neck 17:226–231, 1995; Curr Prob Derm VI Jan/Feb 1994; Clin Exp Derm 11:183–187, 1986; JAAD 13:481–496, 1985

Impetigo, bullous

Mastocytosis, localized cutaneous JAAD 15:291–293, 1986

Infectious eczematoid dermatitis

Scleromyxedema (lichen myxedematosus)

Dermatomycosis – Bipolaris spp. Cutis 72:313–319, 2003 Erysipelas/cellulitis – primary or recurrent; Milian’s sign ID Cases 14:e00449, 2018; Int Med 56:2381–2382, 2017 Herpes simplex – eczema herpeticum

Insect bite reaction Leishmaniasis JAAD 28:495–497, 1993; JAAD 23:1178, 1990 Leprosy – lepromatous or tuberculoid leprosy Ann Int Med 98:49, 1983; erythema nodosum leprosum AD 122:1435–1440, 1986; swollen red ear – type 1 leprosy reaction AD 145:349–351, 2009; swollen red ear – borderline lepromatous leprosy Clin Inf Dis 50:1015–1016,1068–1069, 2010

INFLAMMATORY DISEASES Erythema multiforme Lymphocytoma cutis Neutrophilic eccrine hidradenitis – red swollen ears AD 139:531– 536, 2003; JAAD 38:1–17, 1998; BJD 128:696–698, 1993

Lobomycosis Cutis 46:227–234, 1990

Perforating folliculitis

Lyme disease (Lyme borreliosis) – erythema migrans; solitary lymphocytoma JAAD 24:621–625, 1991; lymphocytoma cutis; earlobe bluish-red plaque JAAD 49:363–392, 2003

Pyoderma gangrenosum J Clin Gastroenterol 11:561–564, 1989;

Mycobacterium avium-intracellulare – red indurated plaque of scalp, ear, and lateral face J Drugs in Dermatol 1:490–491, 2013 Mycobacterium bovis – lupus vulgaris BJD 153:220222, 2005 Mycobacterium tuberculosis – lupus vulgaris – “turkey ear” SKINmed 10:42–43, 2012; BJD 157:816–818, 2007; – extensive destruction Cutis 15:499–509, 1975; starts as red-brown plaque, enlarges with serpiginous margin or as discoid plaques; apple-jelly nodules JAAD 18:581–583, 1988; Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960; ear piercing J Pediatr 40:482–485, 2009; J Pediatr 40:482–485, 1952 Myiasis – Cochliomyia hominivorax (New World screwworm) – deposition of larvae in triangular fossa JAAD 27:264–265, 1992 Necrotizing fasciitis (Streptococcal gangrene) Otolaryngol Head Neck Surg 113:467–473, 1995 Otitis externa Clin Otolaryngol 17:150–154, 1992; Arch Environ Health 37:300–305, 1982; malignant otitis externa – pseudomonas Ear Nose Throat J 73:772–774, 777–778, 1994 Papular acrodermatitis of childhood (hemorrhagic variant) Ped Derm 8:169–171, 1991 Parvovirus B19 infection Pediculosis capitis – elephantiasis of ears Acta DV 63:363–365, 1983

JAAD 18:1084–1088, 1988 Sarcoid – lupus pernio JAAD 16:534–540, 1987; BJD 112:315–322, 1985 Stevens-Johnson syndrome

METABOLIC DISEASES Cold agglutinin disease – painful erythema and edema of ears; thrombotic vasculopathy JAMA Derm 151:785–786, 2015 Cryoglobulinemia Diabetes – reactive perforating collagenosis Fabry's disease – telangiectasia of ears Ped Derm 12:215–219, 1995 Porphyrias – congenital erythropoietic porphyria (Gunther’s disease) – mutilation of the ears Semin Liver Dis 2:154–63, 1982; hepatoerythropoietic porphyria JAAD 11:1103–1111, 1984; AD 116:307–311, 1980 Pretibial myxedema AD 122:85–88, 1986

NEOPLASTIC Basal cell carcinoma – in linear nevus sebaceus syndrome JAAD 29:109–111, 1993

298 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Eccrine spiradenomas (multiple) with trichoepitheliomas Cutis 46:46–50, 1990

Lichen simplex chronicus

Eruptive keratoacanthomas JAAD 29:299–304, 1993 Kaposi's sarcoma JAAD 38:143–175, 1998; Int J Dermatol 36:735–740, 1997; Dermatology 190:324–326, 1995

Psoriasis – relapsing polychondritis-like appearance of ears in patients with psoriasis and psoriatic arthritis JAAD 64:1006–1007, 2011; JAAD 20:130–132, 1989; J Rheumatol 14:162–164, 1987; NEJM 263:51058, 1960

Keratoacanthomas of Grzybowski – personal observation

Seborrheic dermatitis

Extramammary Paget's disease AD 131:951–956, 1995

Leukemia cutis – acute myelogenous leukemia; recurrent edema and erythema of ears J Dermatol 31:748–751, 2001 Lymphoma – cutaneous T-cell lymphoma (CTCL) Sezary syndrome; lymphomatoid granulomatosis (angiocentric lymphoma) – purple ear JAAD 20:571–578, 1989; composite T- and B-cell lymphoma of earlobe BJD 143:439–444, 2000; marginal zone B-cell lymphoma (MALT) – red earlobe JAAD 58:S62–63, 2008; histiocytic lymphoma

Pityriasis rubra pilaris

PSYCHOCUTANEOUS DISEASES Delusions of parasitosis Factitial dermatitis

Seborrheic keratosis

SYNDROMES

Squamous cell carcinoma

Antiphospholipid antibody syndrome (purple ear) JAAD 22:356– 359, 1990

Waldenstrom's macroglobulinemia BJD 106:217, 1982 Xanthogranuloma - adult onset JAAD 32:372–374, 1995

PARANEOPLASTIC DISORDERS Bazex syndrome (acrokeratosis paraneoplastica) – psoriasiform dermatitis of helices JAAD 55:1103–1105, 2006; Cutis 74:289–292, 2004; JAAD 16:178–183, 1987; AD 120:502–504, 1984; Paris Med 43:234–237, 1922

PHOTODERMATITIS Actinic prurigo – red ear lobule JAAD 44:952–956, 2001 Chronic actinic dermatitis AD 126:317–323, 1990 Dermatoheliosis – erythema, telangiectasia HIV photosensitivity Juvenile spring eruption (atopic) (lambing ears) BJD 168:1066– 1072, 2013 Polymorphic light eruption AD 117:186–187, 1981

Ataxia telangiectasia – linear telangiectasias of conchal bowl Ann Int Med 99:367–379, 1983 Cardio-facio-cutaneous syndrome Cowden's syndrome Dermochondrocorneal dystrophy AD 124:424–428, 1988 Erythromelalgia Ped Derm 36:686–689, 2019 Erythro-otalgia Pre-AAD Pediatric Dermatology Meeting, March, 2000 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) Am J Med 82:989–997, 1987 Juvenile hyaline fibromatosis Ped Derm 7:68–75, 1989 KID syndrome – keratosis, ichthyosis, deafness syndrome – fixed orange, symmetrical hyperkeratotic plaques of scalp, ears, and face with perioral rugae; aged or leonine facies; erythrokeratoderma-like; later hyperkeratotic nodules develop Ped Derm 13:105–113, 1996; Ped Derm 17:115–117, 2000 MAGIC syndrome (Behcet's disease and relapsing polychondritis) AD 126:940–944, 1990 Multicentric reticulohistiocytosis Clin Rheum 15:62–66, 1996

PRIMARY CUTANEOUS DISEASES Acne rosacea – rhinophyma of the ears AD 134:679–683, 1998; granulomatous rosacea Alopecia mucinosa Angiolymphoid hyperplasia with eosinophilia AD 130:369–374, 1994; JAAD 19:345–349, 1988; JAAD 12:781–796, 1985 Atopic dermatitis Darier's disease – mimicking dermatitis J Laryngol Otol 106:725– 726, 1992 Elastosis perforans serpiginosa Elephantiasis – red swollen ears; dermatitis, psoriasis, chronic streptococcal infection, head lice Cutis 29:441–444, 1982; Acta DV (Stockh) 63:363–365, 1983

PHACES syndrome Red ear syndrome – may be manifestation of erythromelalgia; irritation of third cervical root; temporomandibular joint dysfunction, thalamic syndrome, headache, antiphospholipid antibody syndrome, neuropsychiatric lupus erythematosus, idiopathic; red hands and feet Ped Derm 36:686–689, 2019; Lupus 9:301–303, 2000; Neurology 47:617, 620, 1996; rare migraine variant Reticular erythematous mucinosis syndrome (REM syndrome) Rombo syndrome – acral erythema, cyanotic redness, follicular atrophy (atrophoderma vermiculata), milia-like papules, telangiectasias, red ears with telangiectasia, thin eyebrows, sparse beard hair, basal cell carcinomas, short stature BJD 144:1215–1218, 2001 Sweet’s syndrome J Laryngol Otol 118:48–49, 2004 Xeroderma pigmentosum

Epidermolytic hyperkeratosis Granuloma annulare Hydroa vacciniforme Ped Derm 21:555–557, 2004

TRAUMA

Keratosis pilaris rubra (keratosis rubra pilaris) AD 142:1611–1616, 2006

Acupuncture – chondritis or perichondritis Laryngoscope 91:422– 431, 1981; Laryngoscope 86:664–673, 1976

Kyrle’s disease

Acute chondritis – burns, frostbite, post-surgical, hematoma

Edema

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Burns – thermal or chemical; chondritis or perichondritis Laryngoscope 91:422–431, 1981; Laryngoscope 86:664–673, 1976

Bullous pemphigoid – appearance in lymphedematous extremity Acta DV (Stockh) 73:461–464, 1993

Child abuse – erythema and petechia of ear due to head slap

Congenital lymphedema with hypogammaglobulinemia or selective IgA deficiency Scott Med J 41:22–23, 1996; Postgrad Med J 64:63–65, 1988

Ear piercing – irritant or allergic contact dermatitis (nickel, gold, olive wood, copper, cobalt, chromium, topical antibiotics, dressings), bleeding, infection, edema and hematoma, earlobe tear Frictional erythema Frostbite – chondritis or perichondritis Laryngoscope 91:422–431, 1981; Laryngoscope 86:664–673, 1976 Hematoma Perniosis/frostbite – vesicles, bullae, ischemic necrosis; calcification Physical trauma – chondritis or perichondritis; sports, telephone, head band Laryngoscope 91:422–431, 1981; Laryngoscope 86:664–673, 1976 Post-surgical perichondritis Pressure – chondritis or perichondritis Laryngoscope 91:422–431, 1981; Laryngoscope 86:664–673, 1976 Pseudocyst of the auricle Radiation dermatitis

Connective tissue panniculitis Dermatomyositis – generalized total body edema (anasarca) JAAD 66:144–147, 2012; Rheumatol Int 29:565–567, 2009; Eur J Pediatr 167:831–834, 2008; J Child Neurol 23:1353–1356, 2008; Indian Pediatr 41:752–753, 2004; J Pediatr 138:942–945, 2001 GATA2 deficiency (includes MONOMAC syndrome, DCML, Emberger syndrome (lymphedema and myelodysplasia) (familial acute leukemia and myelodysplasia) – monocytopenia, B-cell and natural killer cell lymphopenia, myeloid leukemias, disseminated mycobacterial infection, human papilloma virus infection, fungal infection; GATA2-transcription factor in early hematopoietic differentiation and lymphatic and vascular development; primary alveolar proteinosis; panniculitis; erythema nodosum-like lesions; primary lymphedema; skin tumors, Sweet’s syndrome with myelodysplastic syndrome BJD 178:781–785, 2018;

Sunburn

BJD 178:593–594, 2018; JAAD 73:367–381, 2015; JAAD 71:577– 580, 2014; BJD 170:1182–1186, 2014

Wrestler’s ear

Lupus erythematosus

VASCULAR DISEASES

Morphea – lymphedema of arms and legs Ped Derm 27:58–61, 2010; generalized morphea – non-pitting edema of trunk and extremities; unilateral edema and bullae preceding linear morphea Ped Derm 24:147–150, 2007

Acute hemorrhagic edema of infancy – purpura in cockade pattern of face, cheeks, eyelids, and ears; may form reticulate pattern; edema of penis and scrotum Cutis 68:127–129, 2001; JAAD 23:347–350, 1990; necrotic lesions of the ears, urticarial lesions; oral petechiae JAAD 23:347–350, 1990; Ann Pediatr 22:599–606, 1975

Rheumatoid arthritis – lymphedema of upper extremities J Rheumatol 22:214–217, 1995 Scleroderma NEJM 372:1056–167, 2015 Urticaria – urticaria of vulva

Arteriovenous malformation JAAD 56:353–370, 2007 Benign (reactive) angioendotheliomatosis – red-brown or violaceous nodules or plaques JAAD 38:143–175, 1998 Erythromelalgia Am J Otolaryngol 25:251–254, 2004; pediatric erythromelalgia – mutation in SCN9A; encodes sodium channel protein Na(v)1.7 subunit – red feet, red hands, red legs (cellulitislike), red face, ears, nose; purple hue, cool, painful JAAD 66:416– 423, 2012 Flushing reactions (see differential diagnosis of flushing) Henoch-Schonlein purpura Granulomatosis with polyangiitis with auricular chondritis – red, swollen ear JAAD 31:605–612, 1994; NEJM 312:1695, 1985; J Rheumatol 7:915, 1980; Arthritis Rheum 20:1286, 1977

CONGENITAL DISEASES Abdominoscrotal hydrocele – lower abdominal swelling and scrotal enlargement; differential diagnosis includes hydrocele, nonincarcerated inguinal hernia, varicocele, spermatocele, nephrotic syndrome, testicular torsion, and testicular cancer JAMA 306:1709–1710, 2011 Congenital lymphedema, hypoparathyroidism, nephropathy, prolapsing mitral valve and brachytelephalangy Facial hemihypertrophy Infantile cortical hyperostosis Lymphedema and cerebral arterio-venous anomaly Lymphedema and microcephaly

Vasculitis

Lymphedema and ptosis

Venous lake

Lymphedema precox McCune-Albright syndrome

EDEMA  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis of hand with lymphedema of arm Contact Dermatitis 9:517–518, 1983; of vulva BJD 126:52–56, 1992; poison ivy

Neonatal cold injury Raised limb bands BJD 147:359–363, 2002 Sturge-Weber syndrome

DEGENERATIVE DISORDERS Muscle disuse

Angioedema – lips, eyelids, genitalia JAAD 25:155–161, 1991

Paralysis

Autoinflammatory syndrome with lymphedema (AISLE) – fever and urticarial, progressive edema of scrotum and legs; mutation in MyoD family inhibitor domain-containing protein

DRUG-INDUCED

Ped Derm 33:602–614, 2016

Acyclovir therapy – peripheral edema JAAD 18:1142–1143, 1988

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Arthus reaction – erythema, edema, hemorrhage, occasional necrosis

Felodipine – erythromelalgia Cutis 75:37–40, 2005

Infant Mex 38:355–361, 1981; preseptal cellulitis and cicatricial ectropion Acta Ophthalmol Scand 79:208–209, 2001; Br J Opthalmol 76:753–754, 1992; Ophthalmic Physiol Opt 10:300–301, 1990; injection anthrax at site of heroin abuse; edema at site of injection; edema, necrosis, bullae, compartment syndrome, necrotizing fasciitis Clin Inf Dis 61:1840–1849, 2015; Eur Surveill 19:20877, 2014

GCSF – recombinant human GCSF; livedo reticularis, edema, with thrombotic and necrotizing panniculitis BJD 142:834–836, 2000

Arthropod bite – hypersensitivity to mosquito bites with intense erythema and edema AD 139:1601–1607

Imatinib (signal transduction inhibitor) – edema of face, forearms, ankles JAAD 58:545–570, 2008; JAAD 48:201–206, 2003

Bee and wasp stings NEJM 133:523–527, 1994

Bromocriptine – erythromelalgia Cutis 75:37–40, 2005 Dilantin hypersensitivity reaction – edema of foot; personal observation

Imiquimod – edema of penis JAMA Derm 150:1370–1371, 2014 Interferon alpha-induced anasarca JAAD 37:118–120, 1997 Methysergide – retroperitoneal fibrosis Nicardipine – erythromelalgia Cutis 75:37–40, 2005 Nifedipine – erythromelalgia Cutis 75:37–40, 2005 Pergolide – erythromelalgia Cutis 75:37–40, 2005 Radiation recall – capecitabine, doxorubicin, taxanes, gemcitabine; erythema and desquamation; edema; vesicles and papules; ulceration and skin necrosis The Oncologist 15:1227–1237, 2010 Sirolimus – lymphedema of legs BJD 160:1322–1326, 2009; renal transplant patient at site of arteriovenous fistula JAMA Derm 150:1023, 2014

Bristleworms (marine) – rash and edema JAAD 61:733–750, 2009 Brucellosis Cutis 63:25–27, 1999; AD 117:40–42, 1981; Brucella epididymoorchitis – scrotal swelling, pain, fever, diaphoresis Clin Inf Dis 33:2017–2027, 2001 Calymmatobacterium granulomatis (Donovanosis) – granuloma inguinale J Clin Inf Dis 25:24–32, 1997; vulvar edema Genitourin Med 63:54–56, 1987 Cat scratch disease Caterpillar dermatitis – Megalopyge caterpillars – burning pain, spreading erythema, edema, lymphangitis; systemic reactions JAAD 62:1–10, 2010; JAMA 175:1155–1158, 1961; saddleback caterpillar (Acharia stimulea), Io moth (Automeris io), hag moth (Phobetron pithecium), buck moth (Hemileuca maia) Cutis 80:110–112, 2007

Sunitinib (multikinase inhibitor) – periorbital and facial edema JAAD 58:545–570, 2008

Cellulitis – acute or recurrent with subtle edema of toes and forefoot; recurrent cellulitis with lymphostasis – personal observation

Toxic epidermal necrolysis – localized to lymphedematous extremity Clin Exp Dermatol 17:456–457, 1991

Centipede bites – erythema and edema JAAD 67:347–354, 2012; Cutis 37:241, 1986; centipede contact dermatitis Dermatophytid – angioedema Ped Derm 32:635–640, 2015

EXOGENOUS AGENTS

Dirofilaria Cutis 72:269–272, 2003

Aquagenic angioedema Cutis 37:465–466, 1986

Dracunculosis – Dracunculus medinensis – initially fever, pruritus, urticaria, painful edema Int J Zoonoses 12:147–149, 1985

Hair penetration of toe cleft skin – edema of the dorsum of the foot; pinhole sinus in interdigital space Liquid nitrogen spray – subcutaneous emphysema JAAD 55:S95– 96, 2006 Paraffinoma – sclerosing lipogranuloma; swelling of penis JAAD 64:1–34, 2011 Podoconiosis – silica microparticles in sole from long-term barefoot exposure to irritant volcanic soils; non-filiarial lymphedema BJD 159:903–906, 2008; JAAD 59:324–331, 2008 Salivary vulvitis Obstet Gynecol 37:238–240, 1971 Seminal vulvitis – vulvar edema, erythema, pruritus Am J Obstet Gynecol 126:442–444, 1976 Silicone – linear edema, nodularity, scarring, and bound-down skin due to leakage of silicone breast implant AD 131:54–56, 1995 Vaccination – extensive limb swelling Clin Inf Dis 37:351–358, 2003

INFECTIONS AND INFESTATIONS Anthrax (malignant pustule) – Bacillus anthracis; painless ulcer with vesicular lesions and surrounding edema; swollen eyelids; face, neck, hands, fingers, arms, foot, knee; starts as painless erythema evolving into papule then into multiple vesicles or bulla on red base; then ulcer with hemorrhagic crust (eschar) with edema and erythema with small vesicles; edema of surrounding skin; takes six weeks to heal; edema of eyelids, lips, perioral area; slaughtering or milking of ill cows, sheep, or goats; handling of raw meat Ped Derm 27:600–606, 2010; Ped Derm 18:456–457, 2001; Br J Opthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp

Ehrlichiosis – macular and papular erosions, petechiae, edema, vesicles, purpuric plaques JAAD 75:1–16, 2016 Eikenella corrodens – cellulitis Clin Infect Dis 33:54–61, 2001 Erysipelas – primary or recurrent; post-infectious lymphedema; including scalp edema; penile erysipelas – edematous penis and/or scrotum with or without necrosis; may result in chronic lymphedema Genital Skin Disorders, Fischer and Margesson, Mosby, 1998, p.20–23 Entophthomucormycosis including basidiobolomycosis and conidiobolomycosis Filariasis – secondary lymphedema; Wuchereria bancrofti, Brugia malayi, Brugia timori; mosquito vector – first sign is edema, pain, and erythema of arms, legs, or scrotum or vulva; chronically lower leg edema, or edema of breast, arms, genitalia with elephantiasis develop JAAD 73:929–944, 2015; Dermatol Clin 7:313–321, 1989; Lymphology 18:148–168, 1985 Fish stings – venomous fish; lesser weever fish, spiny dogfish, stingray, scorpion fish, catfish, rabbit fish, stone fish, stargazers, toadfish – erythema, edema mimicking cellulitis Gnathostomiasis – migratory subcutaneous swellings; painful and red; upper body and periorbitally Clin Inf Dis 16:33–50, 1993; urticarial migratory lesions; nodules; subcutaneous hemorrhages along tracks of migration; abdominal pain, nausea and vomiting, diarrhea; South East Asia JAAD 73:929–944, 2015; JAAD 73:929– 944, 2015; JAAD 11:738–740, 1984; AD 120:508–510, 1984 Granuloma inguinale (donovanosis) – vulvar lymphedema Genitourin Med 63:54–56, 1987 Herpes simplex

Edema Herpes zoster Human herpesvirus 8 – relapsing inflammatory syndrome; fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, exanthema of hands, wrists, and elbows NEJM 353:156–163, 2005 Lassa fever (Old World Arenavirus) – edema due to capillary leak syndrome

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Schistosomiasis of scrotum with pseudo-elephantiasis; fever, edema, urticarial eruption, headache, arthralgias, abdominal pain, hypereosinophilia occurring 4–6 weeks after infection BJD 135:110–112, 1996; Katayama fever – edema of arms and legs, genitalia JAAD 73:929–944, 2015 Scorpion sting – edema Cutis 57:139–141, 1996

Leprosy – type 1 reaction demonstrates reappearance of resolved lesions, with erythema, edema, and paresthesias; acute peripheral neuritis, edema of hands, feet, arms, and face JAAD 83:17–30, 2020; BJD 158:648–649, 2008; JAAD 57:914–917, 2007

Sea urchins – initial edema Clin Exp Dermatol 2:405–407, 1977

Loiasis – Calabar swellings (localized angioedema); pruritic transient localized subcutaneous swellings; focal angioedema, periorbital edema; worm across conjunctiva JAAD 73:929–944, 2015; Clin Inf Dis 60:55–63, 2015; temporary of arm and hand, and elsewhere; angioedema

Spider bites – black widow spider (Latrodectus mactans) – punctum with erythema and edema AD 123:41–43, 1987; brown recluse spider (Loxosceles reclusa) – erythema, edema, central bulla; targetoid lesion with central blue/purple, ischemic halo, outer rim of erythema; at 3–4 days central necrosis, eschar, ulcer, scar South Med J 69:887–891, 1976; wolf spider (Lycosa) – erythema and edema Cutis 39:113–114, 1987

Lymphangitis, infectious (post-cellulitis, erysipelas) Lymphogranuloma venereum – genital lymphedema leading to vulvar elephantiasis or “saxphone penis”; inguinal adenitis with abscess formation and draining chronic sinus tracts; rectal syndrome in women with pelvic adenopathy, periproctitis with rectal stricture and fistulae; esthiomene – scarring and fistulae of the buttocks and thighs with elephantiasic lymphedema of the vulva; lymphatics may develop abscesses which drain and form ulcers Int J Dermatol 15:26–33, 1976 Malignant otitis externa – edema of soft tissues around ear Am J Med 71:603–614, 1981 Mansonella perstans – pericardial inflammation, subcutaneous nodules, peritoneal or pleural cavity involvement, angioedema, pruritus, fever, headaches, arthralgias, neurologic symptoms JAAD 75:19–30, 2016 Mites and ticks – erythema, edema, papules JAAD 67:347–354, 2012 Mycobacterium tuberculosis – lupus vulgaris; starts as red-brown plaque, enlarges with serpiginous margin or as discoid plaques; apple-jelly nodules; myxomatous form with large tumors of the earlobes; lymphedema prominent; head, neck, around nose, extremities, trunk Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960; inguinal lymphadenopathy with genitocrural lymphedema Necrotizing fasciitis AD 138:893–898, 2002; JAAD 20:774–781, 1989; appearance in lymphedematous extremity Int J Derm 29:41–44, 1990 Onchocerciasis – localized edema – swelling of one arm West Afr Med J 11:83–84, 1962; Mazzotti reaction – swelling during therapy Osteomyelitis of the skull – Pott's puffy tumor – scalp edema AD 121:548–549, 1985; of the foot – personal observation Paragonimiasis (Paragonimus westermani) Parechovirus type 3 – young infants; high fever, poor perfusion, irritability; sepsis-like presentation; erythrodermic rash, abdominal distension, edema, hepatitis; recovery common Clin Inf Dis 60:228–236, 2015 Parvovirus B19, congenital – pallor, maceration, and subcutaneous edema Textbook of Neonatal Dermatology, p.214, 2001; bullous papular–purpuric gloves and socks syndrome – starts with edema and erythema of hands and feet JAAD 60:691–695, 2009 Pediculosis – head lice with elephantiasis of the ear Acta DV (Stockh) 63:363–365, 1983 Pyomyositis – with purpura JAAD 10:391–394, 1984; faint erythema overlying edema JAAD 51:308–314, 2004 Sandfly bites – edema of limbs

Snake bites – edema, erythema, pain, and necrosis NEJM 347:347–356, 2002; Med J Aust 159:773–779, 1993 Sparganosis – edematous painful nodules; chronic elephantiasis

Stingray envenomation – erythema and edema due to spines on dorsum of tail JAAD 61:733–750, 2009 Streptococcal infection J Clin Inf Dis 24:516–517, 1997; vulvar edema due to repeated infection J Obstet Gynecol 67:279–280, 1960 Streptococcal toxic shock syndrome – painful localized edema and erythema; progression to vesicles and bullae Syphilis – penile edema in secondary syphilis Indian Dermatol Online J 10:585–586, 2019; leg edema with syphilitic membranous glomerulonephritis; rash and nephrotic syndrome Am J Med 130:285–287, 2017 Trichinosis Trichomoniasis – vulvar edema and erythema Clin Obstet Gynecol 24:407–438, 1981 Trypanosomiasis, American (Chagas’ disease) – cutaneous inoculation (inoculation chagoma); edema with exanthems; edema in chronic Chagasic cardiomyopathy Vibrio vulnificus – edema, erythema, and purpura of ankles BJD 145:280–284, 2001 Zika virus – fever, morbilliform (macular and papular exanthem), arthralgia, conjunctivitis, myalgia, headache, retro-orbital pain, edema of hands and feet; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) JAAD 74:1286–1287, 2016; NEJM 360:2536–2543, 2009 Zygomycosis – edema with black discoloration J Urol 161:1906– 1907, 1999; subcutaneous zygomycosis – Conidiobolus coronatus – lower facial edema AD 124:1392–1396, 1988; Basidiobolus – involves limb or limb-girdle areas in children

INFILTRATIVE DISEASES Amyloidosis – primary systemic; lymphedema of lower extremities Ann Rehab Med 41:887–891, 2017; cardiac and renal amyloid; amyloid granulomatous hepatitis Int Arab Med 5:29, 2012 Mucopolysaccharidoses – edema of hands and feet; personal observation Rosai-Dorfman disease – bilateral eyelid edema Ped Derm 26:633–635, 2009 Scleromyxedema

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INFLAMMATORY DISEASES Atypical lymphocytic lobular panniculitis (T cell dyscrasia) – spontaneously resolves; red plaques and nodules of arms and legs with associated edema; identical presentation as subcutaneous panniculitis-like T-cell lymphoma with hemophagocytosis JAAD 61:875–881, 2009; J Cutan Pathol 31:300–306, 2004

Diabetes – diabetic muscle infarction – swelling of thigh AD 143:1456–1457, 2007; Diabetalogica 1:39–42, 1965; cold, swollen, dry feet Fabry's disease (angiokeratoma corporis diffusum) – edema of hands, arms, eyelids AD 140:1526–1527, 2004

Atypical neutrophilic infiltrate – appearance in lymphedematous extremity Dermatologica 183:230–233, 1991

GM1 gangliosidosis – generalized edema in infancy; coarse facies Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.132–133

Crohn's disease – facial edema; lip edema; penile and scrotal edema, erythema, and fistulae Ped Derm 35:566–574, 2018; JAAD 77:795–806, 2017; JAAD 70:385, 2014; JAAD 36:697–704, 1997; vulvar edema with lymphangiectasias Genitourin Med 65:335–337, 1989; granulomatous lymphangitis – penile and scrotal edema Ped Derm 33:172–177, 2016; Ped Derm 29:765–766, 2012; Ped Derm 27:279–281, 2010; JAAD:S182–183, 2003

Gout – edema of the foot; personal observation Hartnup's disease – edema due to hypoproteinemia and liver disease Pediatrics 31:29–38, 1963; autosomal recessive; defective transport of tryptophan in small intestine and kidneys; pellagra-like photosensitive eruption; cerebellar ataxia; psoriasiform red scaly plaques, generalized alopecia, widespread edema Ped Derm 23:262–265, 2006

Eosinophilic fasciitis – presenting as pitting edema of the extremities Am J Med 111:318–320, 2001

Heavy chain disease (Franklin’s disease) – palatal edema AD 124:1538–1540, 1988

Erythema induratum (Whitfield) – nodules with edematous ankles

Hemochromatosis, neonatal AD 132:1507–1512, 1996

Hidradenitis suppurativa – vulvar lymphedema Urology 44:606–608, 1994; scrotal elephantiasis JAAD 64:993–994, 2011; scrotal edema Plast Reconstr Surg 97:1243–1245, 1996

Hypoalbuminemia

Inflammation – secondary lymphedema Lymphangitis – secondary lymphedema Neutrophilic eccrine hidradenitis – localized edema Arch Ophthalmol 112:1460– 1463, 1994 Panniculitis Pyoderma gangrenosum – vulvar edema BJD 157:1235–1239, 2007 Retractile mesenteritis (IgG4 disease) – edema of abdominal wall, lower extremities, genitalia- personal observation Sarcoid – lymphedema; unilateral leg edema JAAD 44:725–743, 2001; bilateral leg edema Am J Med Sci 318:413–414, 1999; Synovitis of the wrists, carpal joints, and fingers with pain swelling and pitting edema (boxing glove hand) or feet Clin exp Rheumatol 18:553–555, 2000

METABOLIC DISEASES Alpha-1 anti-trypsin deficiency panniculitis with anasarca, generalized edema, pulmonary embolus, and hypogammaglobulinemia; violaceous nodule with yellow pseudovesicles and telangiectasias; ulcerated red nodules BJD 173:289–291, 2015 Anasarca – edema of breast Beriberi (Vitamin B1, thiamine deficiency) – anorexia, weakness, constipation, polyneuritis, cardiac failure with edema, muscle wasting; atrophic glossitis JAAD 21:15–18, 1989 Cardiac disease – congestive heart failure; constrictive pericarditis; edema of breast Congenital disorders of glycosylation (CDG-Ix) – nuchal skin folds, facial dysmorphism, inverted nipples, hypoplastic nails, petechiae and ecchymoses, edema; neurologic, gastrointestinal and genitourinary abnormalities, pericardial effusion, ascites, oligohydramnios Ped Derm 22:457–460, 2005 Cryofibrinogenemia – of dorsal feet Am J Med 116:332–337, 2004 Cystic fibrosis – diaper dermatitis and generalized edema AD 146:171–174, 2010

Hypoparathyroidism – puffy skin JAAD 17:921–940, 1989 Hypothyroidism – edematous and indurated skin; myxedema – also massive localized lymphedema of hypothyroidism Hum Pathol 31:1162–1168, 2000 Kwashiorkor – generalized edema and protuberant abdomen; and “flaky paint” desquamation; varnished hyperkeratosis, dry brittle hair, alternate normal/red bands of hair color JAMA Derm 150:910–911, 2014; JAMA Derm 150:85–86, 2014; Cutis 67:321–327, 2001 ; JAAD 52:S69–72, 2005; AD 137:630–636, 2001; Cutis 67:321–327, 2001; Ped Derm 16:95–102, 1999; facial edema AD 134:107–108, 1998 Liver disease, chronic Menstruation Nephrogenic fibrosing dermopathy (nephrogenic systemic fibrosis) – presenting with anasarca JAAD 48:55–60, 2003; nephrogenic systemic fibrosis with superior vena cava syndrome J Drugs in Dermatol 13:615–618, 2014 Nephrotic syndrome or other forms of chronic renal disease; edema of breast Oasthouse disease – white hair, recurrent edema; increased serum methionine Obesity – lymphedematous mucinosis of the abdomen and legs of obesity JAAD 81:1037–1057, 2019; pendulous abdomen with edema due to lipodermatosclerosis Clin Exp Dermatol 18:164–166, 1993; massive localized lymphedema – red indurated abdominal skin mass with bullae and peau d’orange appearance JAAD 59:S109–110, 2008; massive localized lymphedema of thigh Hum Pathol 31:1162–1168, 2000; Am J Surg Pathol 22:1277–1283, 1998 Porphyrias – erythropoietic protoporphyria; acute facial edema Eur J Pediatr 159:719–725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751–766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976 Pregnancy Pretibial myxedema – solid non-pitting edema of shins and feet; elephantiasic form with edema and nodule formation Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged

Edema abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; Ped Derm 13:58–60, 1996; AD 127:124–125, 1991 Refeeding edema (possibly kwashiorkor) AD 145:1202–1203, 2009 Scurvy – peripheral edema JAAD 41:895–906, 1999 Sickle cell disease – hand-foot syndrome; edema of hands and feet due to underlying bone infarction Clin Pediatr 20:311–317, 1981

303

Metastases JAAD 29:228–236, 1993; carcinoma erysipelatoides – includes metastases from breast, lung, melanoma, ovary, stomach, tonsils, pancreas, kidney, rectum, colon, parotid, uterus JAAD 39:876–878, 1998; JAAD 30:304–307, 1994; JAAD 31:877–880, 1994; larynx Eur J Dermatol 11:124–126, 2001; transitional cell carcinoma with penile and scrotal edema JAAD 51:143–145, 2004; JAAD 36:993–995, 1996; elephantiasis-like cutaneous metastases secondary to signet-ring cell carcinoma of the stomach Cutis 44:455–458, 1989; basal cell carcinoma JAAD 59:S1–3, 2008 Squamous cell carcinoma – occurrence in lymphedematous extremity Cancer 54:943–947, 1984

Xanthoma – appearance in lymphedematous extremity J R Soc Med 81:113–114, 1988

PARANEOPLASTIC DISEASES

NEOPLASTIC DISORDERS

Carcinoid syndrome – foregut (stomach, lung, pancreas) – bright red geographic flush, sustained, with burning, lacrimation, wheezing, sweating; hindgut (ileal) – patchy, violaceous, intermixed with pallor, short duration; edema, telangiectasia, cyanotic nose and face, rosacea Acta DV (Stockh) 41:264–276, 1961

Angiosarcoma – scalp edema JAAD 38:837–840, 1998; Cancer 77:2400–2406, 1996; AD 121:549–550, 1985; angiosarcoma in radiation site – late skin thickening and induration, edema, and dyspigmentation JAAD 49:532–538, 2003 Angiosarcoma of the breast post-irradiation for breast cancer – late thickening, edema, or induration of the breast JAAD 49:532–538, 2003 Baker’s cyst, ruptured – swelling and pain of calf Basal cell carcinoma – occurrence in lymphedematous extremity J Derm Surg Onc 14:781–783, 1988

Thrombophlebitis migrans (Trousseau’s sign) – strong association with internal malignancy Circulation 22:780, 1960

PHOTODERMATOSES Ultraviolet recall manifested as edema, erythema, bullae, hemorrhagic crusting, macules, papules, ulceration, necrosis JAAD 56:494–499, 2007

Carcinoma of the breast (primary) Cancer, advanced – recurrent Castleman's disease, including multicentric Castleman’s disease – ascites, pleural effusions JAMA Derm 153:449–452, 2017 Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) – erythroderma and edema AD 138:1208–1212, 2002; AD 128:193– 200, 1992 Kaposi’s sarcoma – edema of legs and feet JAAD 59:179–206, 2008; JAAD 38:143–175, 1998; Dermatology 190:324–326, 1995 Leiomyosarcoma – diffuse swellings NEJM 266:1027–1030, 1962 Leukemia – chronic lymphocytic leukemia Lymphangiosarcoma (Stewart-Treves tumor) – increasing edema in lymphedematous extremity; red-brown or ecchymotic patch, nodules, plaques in lymphedematous limb Arch Surg 94:223–230, 1967; Cancer 1:64–81, 1948 Lymphoma – facial edema in lymphomatoid granulomatosis Postgrad Med J 68:366–368, 1992; AD 127:1693–1698, 1991; cutaneous-T cell lymphoma; angioimmunoblastic lymphadenopathy (T-cell lymphoma) – edema of arms and legs BJD 144:878–884, 2001; hydroa vacciniforme-­like cutaneous T-cell lymphoma (hydroa vacciniforme-like lymphoproliferative disorder), Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 82:534–540, 2019; JAAD 69:112–119, 2013 Malignant eccrine poroma Malignant fibrous histiocytoma – occurrence in lymphedematous extremity J R Soc Med 78:1497–1498, 1985 Malignant histiocytosis mimicking kwashiorkor Ped Derm 19:5–11, 2002 Melanoma – occurrence in lymphedematous extremity J Surg Oncol 30:16–18, 1985

PRIMARY CUTANEOUS DISEASES Acne rosacea – solid facial edema JAAD 17:843–844, 1987; AD 121:87–90, 1985; periorbital chronic edema Acne vulgaris – symmetric or asymmetric facial edema Acta DV (Stockh) 67:535–537, 1987 Acrodermatitis chronica atrophicans – bluish-red edema of extremities BJD 147:375–378, 2002; cutaneous Borreliosis – acrodermatitis chronica atrophicans, cutis laxa-like changes, red patches, erythema migrans, erythema and edema of foot, poikilodermatous changes, red macules and telangiectasias JAAD 72:683–689, 2015 Blepharochalasis – recurrent eyelid edema with ptosis AD 145:498– 499, 2009; Br J Ophthalmol 72:863–867, 1988; AD 115:479–481, 1979 Milroy-like syndrome – mutation in VEGFC FLT4 BJD 175:628–631, 2016 Cutis laxa – generalized cutis laxa – autosomal dominant – lesions often preceded in infancy by episodes of edema; infantile genitalia; scant body hair; bloodhound appearance of premature aging Ped Derm 19:412–414, 2002 Idiopathic edema – fluid retention syndrome Clin Exp Dermatol 3:411–416, 1978 Lipedema – edema of legs, thighs, and hips; sparing of feet J Dtsch Dermatol Ges 11:225–233, 2013; BJD 166:161–168, 2012; Ann Rehabil Med 35:922–927, 2011; BJD 163:296–301, 2010; JAAD 50:969–972, 2004; Plast Reconstr Surg 94:841–847, 1994; Mayo Clin Proc 15:184–187, 1940 Lipedematous alopecia (S) – boggy (“spongy”) scalp with diffuse alopecia; seen particularly in black women Cutis 80:321–324, 2007; JAAD 52:152–156, 2005; AD 138:1517–1518, 2002; J Cutan Pathol 27:49–53, 2000; Dermatology 201:168–170, 2000; Cutis 65:199– 202, 2000; J Cutan Pathol 27:49–53, 2000; AD 134:499–500,

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

502–503, 1998; AD 130:802–803, 1994; AD 89:819–820, 1964; AD 84:619–622, 1961; Arch Dermatol Syphilol 32:688, 1935 Lipedematous scalp Ped Derm 23:276–278, 2006 Lipschutz ulcer (ulcus vulvae acutum) – vulvar erythema and edema accompanying aphthous ulcers of the vulva Ped Derm 25:113–115, 2008 Pachydermodactyly with knuckle pads – swollen joints; benign soft tissue fibromatosis, joint pain Ped Derm 34:719–720, 2017; Rheumatologia 54:136–140, 2016; AD 11:524, 1975 Pityriasis rubra pilaris – peripheral edema accompanying erythroderma Primary lymphedema – mutation in endothelial growth factor receptor 3 involving NF-kB pathway Psoriatic arthritis – lymphedema of arms Semin Arthr Rheum 22:350–356, 1993 Scleredema of Buschke (pseudoscleroderma) JAAD 11:128–134, 1984 Testicular torsion – as a complication of a congenital hydrocele; red painful swollen scrotum NEJM 361:698, 2009 Weeping scrotum

PSYCHOCUTANEOUS DISEASES Factitial limb edema Ann Hematol 70:57–58, 1995; due to factitial application of tourniquet (elastic band, clothing) (Secretan’s syndrome) Plast Reconstr Surg 65:182–187, 1980; subcutaneous emphysema Ped Derm 21:205–211, 2004

SYNDROMES Amnion rupture malformation sequence (amniotic band syndrome) – congenital ring constrictions and intrauterine amputations; secondary syndactyly, polydactyly; distal lymphedema JAAD 32:528–529, 1995; Am J Med Genet 42:470–479, 1992; Cutis 44:64–66, 1989; lymphedema of hand due to constriction bands JAAD 15:296–297, 1986 Anhidrotic ectodermal dysplasia with immunodeficiency – osteopetrosis and lymphedema – mutation in stop codon of NEMO gene JAAD 47:169–187, 2002; Nat Genet 27:277–285, 2001; Am J Hum Genet 67:1555–1562, 2000 Apert's syndrome Behcet’s syndrome – superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of neck with neck vein distension, upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008 Caldwell's syndrome – angioedema and lymphoproliferative disease – acquired angioedema-I(AAE-I) Clin Immunol Immunopathol 1:39–52, 1972 Capillary leak syndrome – generalized edema, shock JAAD 56:339–342, 2007 Cardio-facio-cutaneous syndrome – lymphedema Cervical rib syndrome (scalene anticus syndrome) – indurated edema Charcot-Marie-Tooth disease – personal observation CHARGE syndrome – primary lymphedema, short stature, coloboma of the eye, heart anomalies, choanal atresia, somatic and mental retardation, genitourinary abnormalities, ear anomalies Ped Derm 20:247–248, 2003

Cornelia de Lange (Brachmann-de Lange) syndrome – generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, posterior neck, and arms, low set ears, arched palate, antimongoloid palpebrae; congenital eyelashes; xerosis, especially over hands and feet, nevi, facial cyanosis, lymphedema Ped Derm 24:421–423, 2007; JAAD 56:541–564, 2007; JAAD 48:161–179, 2003; JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993 Cronkhite-Canada syndrome Cutis 61:229–232, 1998 Distichiasis-lymphedema syndrome – double row of eyelashes, nuchal webbing BJD 175:628–631, 2016; Ped Derm 19:139–141, 2002; BJD 142:148–152, 2000; AD 135:347–348, 1999; Clin Dysmorphol 3:139–142, 1994; Hum Genet 39:113–116, 1977 Dysplasia epiphysealis hemimelica (Trevor disease, tarsomegaly) – edema of the feet Ectodermal dysplasia and immunodeficiency – lymphedema; NEMO mutation Hum Molec Genet 11:2371–2375, 2002; Pediatrics109:e97, 2002; Nat Genet 27:277–285, 2001; Am J Med Genet 99:172–177, 2001 Emberger syndrome – mutation in GATA2 BJD 175:628–631, 2016 Episodic nontoxic erythema – swelling of the extremities followed by generalized tender sunburn-like erythema, followed by exfoliation AD 132:1387–1388, 1996 Familial Mediterranean fever – edema with or without erythema of the foot AD 134:929–931, 1998 Gardner-Diamond syndrome (painful bruising syndrome) – ecchymoses of arms and legs preceded by edema and erythema JAAD 27:829–832, 1992; Blood 10:675–690, 1955; autosensitization to DNA Ann Int Med 60:886–891, 1964 Generalized lymphedema associated with neurologic signs – facial edema JAAD 72:333–339, 2015 Gorham-Stout (disappearing bone) disease – lymphatic malformations with monostotic or polystotic osteolysis JAAD 56:S21–25, 2007; J Bone Joint Surg Am 37A:985–1004, 1955; Boston Med Surg J 18:368–369, 1838 H syndrome – sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, short stature, facial telangiectasia, gynecomastia, camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly JAAD 59:79–85, 2008 Hemophagocytic syndrome – facial edema edematous rash AD 128:193–200, 1992 Hennekam lymphangiectasia-lymphedema syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, hirsutism, bilateral single palmar crease, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia; mutation in collagen and calcium binding epidermal growth factor domain-containing protein (CCBE1) FLT4 BJD 175:628–631, 2016; JAAD 71:577–580, 2014; JAAD 56:353–

Edema

305

370, 2007; Ped Derm 23:239–242, 2006; Am J Med Genet 34:593–600, 1989

Curr Opin Immunol 16:34–41, 2004; Hum Mol Genet 11:2371–2375, 2002

Hereditary angioedema – serpiginous erythema; triad of circumscribed edema of the skin, laryngeal edema, and abdominal pain; mutation in SERPING1 or Factor XII BJD 173:1102–1104, 2015; JAAD 65:843–850, 2011; BJD 161:1153–1158, 2009; NEJM 359:1027–1036, 2008; Sybert's Genetic Skin Disorders; Hosp TID No.40.1 rk 4:741–747, 1886; Monatsschr Prakt Dermatol 1:129– 131, 1882; Edinb Med J 22:513–526, 1876

Papular-purpuric gloves and socks syndrome Ped Derm 15:413, 1998

Hurler's syndrome and other mucopolysaccharidoses Hypohidrotic ectodermal dysplasia of Zonana with osteopetrosis and lymphedema – lymphedema; mutation in stop codon of NEMO Nat Genet 27:277–285, 2001 Hypotrichosis-telangiectasia-lymphedema syndrome – vascular nevi on palms and soles; autosomal recessive – mutation in SRY-related HMG Box 18 (SOX 18) BJD 175:628–631, 2016; JAAD 71:577–580, 2014; Clin in Dermatol 23:47–55, 2005 Idiopathic retroperitoneal fibrosis Intestinal lymphangiectasia, pes cavus, microcephaly – lymphedema Klippel-Feil anomaly Lymphedema of pubertal onset (Meige type) with cleft palate Cleft Palate J 20:151–157, 1983 Lymphedema with recurrent cholestasis West J Med 137:32–44, 1982 Lymphedema-distichiasis syndrome – mutation in FOXC2 FLT4 BJD 175:628–631, 2016 Lymphedema with intestinal lymphangiectasia West J Med 137:32–44, 1982 Meige syndrome – mutation in GJC2 BJD 175:628–631, 2016 Melkersson-Rosenthal syndrome – orofacial edema Microcephaly-lymphedema syndrome –with short stature Am J Med Genet 280:506–509, 1998 Microcephaly-lymphedema-chorioretinal dysplasia syndrome – edema of upper and lower extremities; autosomal dominant or recessive Ped Derm 22:373–374, 2005 Mulvihill-Smith syndrome – congenital lymphedema Am J Med Genet 69:56–64, 1997 Neu-Laxova syndrome – variable presentation; mild scaling to harlequin ichthyosis appearance; ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema and mildly edematous feet and hands, absent nails; microcephaly, intrauterine growth retardation, limb contractures, low set ears, sloping forehead, short neck; small genitalia, eyelid and lip closures, syndactyly, cleft lip and palate, micrognathia; autosomal recessive; uniformly fatal Ped Derm 20:25–27,78–80, 2003; Curr Prob Derm 14:71–116, 2002; Am J Med Genet 35:55–59, 1990 Neurofibromatosis – hemihypertrophy Neuronal migration defect and cerebellar hypoplasia – lymphedema Noonan's syndrome – webbed neck, short stature, malformed ears, nevi, keloids, transient lymphedema, ulerythema ophyrogenes, keratosis follicularis spinulosa decalvans JAAD 56:353–370, 2007; JAAD 46:161–183, 2002; Ped Derm 15:18–22, 1998; J Med Genet 24:9–13, 1987; extremities Cutis 46:242–246, 1990 Ogilvie’s syndrome – colonic pseudoobstruction due to varicella/ zoster virus infection – personal observation Osteopetrosis-lymphedema-ectodermal dysplasia (OL-HED-ID) syndrome Ped Derm 31:716–721, 2014; AD 144:342–346, 2008;

Peho syndrome – optic atrophy, progressive encephalopathy, hypsarrhythmia POEMS syndrome (Crowe-Fukase syndrome, Takatsuki syndrome) (osteosclerotic myeloma) (PEP syndrome – plasma cell dyscrasia, endocrinopathy, polyneuropathy) – plethora, angiomas (cherry, globular, glomeruloid) presenting as red nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, sclerodermalike changes, either generalized or localized (legs), hyperhidrosis, clubbing, leukonychia, papilledema, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss, fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias; osteosclerotic myeloma (IgG or IgA lambda) bone lesions, progressive symmetric sensorimotor peripheral polyneuropathy, hypothyroidism, and hypogonadism; peripheral edema, thrombocytosis, cutaneous angiomas, blue dermal papules associated with Castleman’s disease (benign reactive angioendotheliomatosis), maculopapular brown-violaceous lesions, purple nodules; papilledema JAAD 58:671–675, 2008; Blood Reviews 21:285–299, 2007; JAAD 55:149–152, 2006; JAAD 44:324–329, 2001; JAAD 40:507–535, 1999; JAAD 40:808–812, 1999; Cutis 61:329–334, 1998; JAAD 21:1061–1068, 1989; AD 124:695–698, 1988; JAAD 12:961–964, 1985; Nippon Shinson 26:2444–2456, 1968 Pseudohypoparathyroidism – dry, scaly, hyperkeratotic puffy skin; multiple subcutaneous osteomas, collagenoma BJD 143:1122– 1124, 2000 SAVI – (STING (stimulator of interferon genes)-associated vasculopathy) – progressive digital necrosis, swelling of fingers, amputation of several digits, violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of arms and legs JAAD 74:186–189, 2016 Thrombocytopenia-absent radius syndrome (TAR syndrome) – edema of feet Triple X syndrome BJD 175:628–631, 2016 Trisomy 21 – congenital lymphedema Hum Reprod 14:823–826, 1999 Trisomy 18 – congenital lymphedema Hum Reprod 14:823–826, 1999 Trisomy 13 – congenital lymphedema Hum Reprod 14:823–826, 1999 Tuberous sclerosis – lymphedema; hemihypertrophy, vascular anomalies, lymphedema Ped Derm 33:536–542, 2016; Ped Derm 28:194–195, 2011 Turner's syndrome – congenital lymphedema of upper and lower extremities and neck, shield chest, wide nipples, micrognathia, low hairline, webbed neck, pigmented nevi, short stature JAAD 56:353–370, 2007; Ped Derm 22:27–275, 2005; JAAD 50:767–776, 2004; lymphedema of scalp may mimic cutis verticis gyrata Ped Derm 15:18–22, 1998 Wells' syndrome (eosinophilic cellulitis) AD 139:933–938, 2003; BJD 140:127–130, 1999; AD 133:1579–1584, 1997; JAAD 33:857–64, 1995; JAAD 18:105–114, 1988; Trans S.Johns Hosp Dermatol Soc 51:46–56, 1971 Whipple’s disease (Tropheryma whipplii) – non-palpable purpura, chronic leg edema, arthralgias; large dilated abdominal lymphatics;

306 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 diarrhea, weight loss, abdominal pain, generalized hyperpigmentation, pulmonary hypertension, eye, cardiovascular, and neurologic disease Clin Infect Dis 41:519–520,557–559, 2005 WILD syndrome – disseminated warts, diminished cell-mediated immunity, primary lymphedema, anogenital dysplasia; perianal hypertrophic plaque AD 144:366–372, 2008 Yellow nail syndrome – lymphedema of hands, legs, and feet; pleural effusion, chronic bronchitis, bronchiectasis J Dtsch Dermatol Ges 12:131–137, 2014; Case Rep Dermatol 3:251–258, 2011; Ped Derm 27:533–534, 2010; Ches 134:375–381, 2008; JAAD 56:537–538, 2007; BJD 156:1230–1234, 2007; JAAD 28:792–794, 1993 BJD 156:1230–1234, 2007; Acta DV (Stockh) 63:554–555, 1983

TOXINS Arsenic – non-pitting edema Dermatol Clinics 29:45–51, 2011 Dieffenbachia picta (Dumb-cane) – chewing the leaves results in perioral edema, salivation, burning, mucosal edema, and blisters causing hoarseness or aphonia Cutis 66:333–334, 2000 Eosinophilia myalgia syndrome (l-tryptophan related) – erythematous and edematous rashes, peripheral edema, morphea, urticaria, papular lesions; arthralgia BJD 127:138–146, 1992; Int J Dermatol 31:223–228, 1992; Mayo Clin Proc 66:457–463, 1991; Ann Int Med 112:758–762, 1990

Subgaleal hematoma – scalp edema AD 121:548–549, 1985 Surgical scar Trench foot, immersion foot Vibration syndrome – edema of hand AD 121:1544–1547, 1985 Vulvar edema X-ray overexposure

VASCULAR DISEASES Aagenaes syndrome (hereditary cholestasis with lymphedema) – autosomal recessive; lymphedema of legs due to congenital lymphatic hypoplasia; pruritus, growth retardation Acute hemorrhagic edema of infancy – facial, earlobe, scrotal, hand edema Arteriovenous fistulae – venous hypertension; abdominal arteriovenous fistulae – lower extremity cyanosis, pulsatile varicose veins, and scrotal edema Cutis 87:284–286, 2011 Achenbach’s syndrome (paroxysmal hematoma of the fingers) – sudden onset of localized edema and pain; associated with a thrombus and/or hematoma JAAD 56:493, 2007; J Hand Surg 27:391–393, 2002; Hautarzt 41:270–271, 1990 Capillary leak syndrome – recurrent idiopathic form or associated with lymphomas, panniculitis, erythrodermic psoriasis, retinoids, BJD 150:150–152, 2004; Ann Int Med 130:905–909, 1999

Potato poisoning – rash of lower abdomen and medial thighs consisting of red papules which progress to pustules and crusted lesions; facial and abdominal edema; headache, vomiting, diarrhea J R Coll Physicians Edinb 36:336–339, 2007

Congenital vein-valve aplasia – onset at puberty

TRAUMA

Erythrocyanosis – may have ulceration, erythema, keratosis pilaris, desquamation, nodular lesions, edema, and fibrosis

Caput succedaneum (scalp edema, neonatal edema) after prolonged labor or precipitous delivery – pressure on parietal and occipital scalp from engagement with cervix, uterus, and vaginal wall during delivery; venous congestion; resolves within a few days Ped Derm 23:533–536, 2006; AD 135:697–703, 1999 Dental treatment – soft tissue cervicofacial emphysema after dental treatment AD 141:1437–1440, 2005 Hematoma Lymph node excision Neonatal cold injury – facial erythema or cyanosis; firm pitting edema of extremities spreads centrally resulting in total body edema; skin is cold; mortality of 25% Br Med J 1:303–309, 1960 Penile fracture – edema and purpura of penis NEJM 372:1055, 2015 Penile venereal edema AD 108:263, 1973; edema from accidentally wrapped hair around the penis Cutis 31:431–432, 1983 Peritoneal laceration – scrotal edema in an infant Adv Perit Dial 9:329–330, 1993

Elephantiasis verrucosa nostra (lymphostasis verrucosa cutis) – lymphedema Endovascular papillary angioendothelioma (Dabska tumor) – diffuse swelling in infant or child Cancer 24:503–509, 1969

Henoch-Schonlein purpura – edema of face preceding onset of HSP Ped Derm 9:311, 1992; facial edema JAAD 37:673–705, 1997 Hypoplastic lymphatics – scrotal edema Ischemia-reperfusion syndrome – occurs after shock, aortic aneurysm repair, release of limb tourniquets, liver transplantation, cardiopulmonary bypass; massive edema Int Wound J March 3, 2014; Semin Vasc Surg 22:52–57, 2009; Plast Reconstr Surg 117:1024–1033, 2006 Kaposiform hemangioendothelioma – with lymphedema BJD 175:833–834, 2016 Kasabach-Merritt syndrome – purpura with edema Ped Derm 35:635–638, 2018 Klippel-Trenaunay-Weber syndrome – lymphedema; venous malformation, arteriovenous fistula, or mixed venous lymphatic malformation Br J Surg 72:232–236, 1985; Arch Gen Med 3:641– 672, 1900; genital lymphedema JAAD 65:893–906, 2011

Physical trauma – secondary lymphedema

Left iliac vein compression – congenital anomaly due to compression by right common iliac; compression by obesity, abdominal masses, bad posture – edema of left ankle

Plantaris muscle tear – swelling and pain of calf Medicine 56:151– 164, 1977

Lymphangioma, diffuse BJD 134:1135–1137, 1996; AD 129:194– 197, 1993

Radiation – secondary lymphedema

Lymphangiomatosis – fluctuant swellings Am J Surg Pathol 16:764–771, 1992

Reflex sympathetic dystrophy (complex regional pain syndrome) – erythema and edema; muscle wasting JAMA Derm 150:640–642, 2014; JAAD 35:843–845, 1996; JAAD 28:29–32, 1993; AD 127:1541–1544, 1991

Lymphangiomyomatosis – lymphedema of one or both legs Cancer 31:455–461, 1973 Lymphedema JAAD 77:995–1006, 2017

Edema, Hands 307  Capillary malformation AVM syndromes, including Parkes-Weber syndrome – RASA1; autosomal dominant   Choanal atresia lymphedema syndrome – mutation in PTPN14  Cholestasis lymphedema syndrome (AAGENAES syndrome) – mutation in LCS1 – autosomal recessive  Congenital (Milroy’s disease), praecox (Meige disease), tarda acquired; mutation in FLT4 BJD 175:628–631, 2016; mutation in VEGFR-3 JAAD 71:577–580, 2014; BJD 163:296–301, 2010; primary upper limb lymphedema BJD 168:272–276, 2013  Ectodermal dysplasia, anhidrosis with immunodeficiency, osteopetrosis, and lymphedema – mutation in IKBKG; x-linked recessive   Fetal chylothorax – mutation in ITGA9 – autosomal recessive  Hennekam lymphangiectasia-lymphedema syndrome – mutation in CCBE1 – autosomal recessive  Hennekam lymphangiectasia-lymphedema syndrome 2 – mutation in FAT4  Hereditary lymphedema type 1A (primary congenital lymphedema) – Nonne-Milroy’s lymphedema – mutation in FLT4 (VEGFR3); autosomal dominant Ped Derm 28:579–580, 2011; JAAD 56:353–370, 2007; Cutis 38:105, 1986; primary familial BJD 163:1358–1360, 2010   Hereditary lymphedema type 1B – autosomal dominant  Hereditary lymphedema type 1C – mutation in GJC2; autosomal dominant  Hereditary lymphedema type 1D (Milroy-like lymphedema) – VEGFC  Hereditary lymphedema type II (Meige’s disease) – mutation in LYMPH2; autosomal dominant  Hypertrichosis-lymphedema-telangiectasia (renal defect) syndrome – mutation in SOX18; autosomal dominant, recessive   Klippel-Trenaunay-Weber syndrome – mutation in KTWS  Lymphedema-distichiasis syndrome – mutation in FOXC2; autosomal dominant   Lymphedema praecox   Lymphedema tarda  Microcephaly chorioretinopathy lymphedema mental retardation syndrome – mutation in KIF11(EGS) – autosomal dominant   Noonan syndrome 1 – mutation in PTPN11; autosomal dominant   Noonan syndrome 4 – mutation in SOS1; autosomal dominant   Noonan syndrome 3 – mutation in KRAS; autosomal dominant  Oculodentodigital dysplasia lymphedema syndrome – mutation in GJA1(CX43) – autosomal dominant  Primary lymphedema with myelodysplasia (Emberger syndrome) – mutation in GATA2; autosomal dominant   Tuberous sclerosis 1 – mutation TSC1; autosomal dominant   Tuberous sclerosis 2 – mutation TSC2; autosomal dominant   Turner’s syndrome – 45XO;SHOX   Yellow nail syndrome – mutation in FOXC27 Parkes-Weber syndrome (multiple arteriovenous anastamosis) Polyarteritis nodosa – angioedema Clin Rheumatol 17:353–356, 1998

Thoracic duct obstruction – non-inflammatory swelling of supraclavicular fossa – obstruction of cervical portion of thoracic duct AD 147:1337–1338, 2011; Vasc Med 9:141–143, 2004; Lymphology 28:118–125, 1995 Thrombophlebitis of axillary vein – personal observation Thrombosis of inferior vena cava due to renal tumor – personal observation Tufted angioma (angioblastoma of Nakagawa) – patchy dull red, purple, or red-brown patch and/or plaque; associated with erythema, edema, and hypertrichosis Ped Derm 30:124–127, 2013 Venous malformation – discrete mass with soft tissue swelling; may be blue or with skin discoloration Ped Derm 30:534–540, 2013 Venous obstruction – multiple causes Venous suffusion, acute Venous thrombosis – swelling and pain of calf; edema of ankle BMJ 320:1453–1456, 2000

EDEMA, HANDS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Airborne allergic contact dermatitis JAAD 15:1–10, 1986 Allergic contact dermatitis Contact Dermatitis 9:517–518, 1983 Angioedema Contact urticaria Dermatomyositis – generalized total body edema JAAD 66:144– 147, 2012; tender hyperkeratotic palmar papules in palmar creases of fingers with central white coloration; dermatomyositis with MDA-5 (CADM-40) (melanoma differentiation-associated gene 5) MDA 5 – RNA-specific helicase; all with interstitial lung disease; ulcers of nail folds, Gottron’s papules, and elbows; these patients demonstrate oral ulcers, hair loss, hand edema, arthritis/arthralgia, diffuse hair loss, punched out ulcers of shoulder or metacarpophalangeal joints, digital necrosis, erythema of elbows and knees (Gottron’s sign), and tender gingiva JAAD 65:25–34, 2011 Polymyalgia rheumatica – RS3PE remitting seronegative, symmetrical synovitis with pitting edema of hands and feet Clin Exp Rheumatol 18:2000 Rheumatoid arthritis – lymphedema of hand and/or arms Ann Rheum Dis 27:167–169, 1968; lymphedema of upper extremities J Rheumatol 22:214–217, 1995; acute onset pitting edema of hands in patients over 50 years old AD 148:1217–1218, 2012 Scleroderma, early – swelling of hands CREST syndrome; linear scleroderma, unilateral Ped Derm 24:147–150, 2007 Sjogren’s syndrome Serum sickness

Post-thrombophlebitis

Urticaria

Pseudo-Kaposi's sarcoma due to arterio-venous fistula (StewartBluefarb syndrome) – ulcerated purple plaque Ped Derm 18:325– 327, 2001; AD 121:1038–1040, 1985

DEGENERATIVE DISEASES

Stasis dermatitis Subclavian vein occlusion – personal observation Superior vena cava syndrome AD 128:953–956, 1992

Sudeck's atrophy – hand edema, Dupuytren's contracture, and Raynaud's phenomenon Syringomyelia – skin of fingers and knuckles becomes cyanotic, thickened, edematous, and keratotic

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DRUGS Acral dysesthesia syndrome – various anti-neoplastic drugs, including cytosine arabinoside, doxorubicin, and polyethylene glycol-coated liposomal doxorubicin AD 136:1475–1480, 2000 DRESS syndrome – multiple drugs

1994; exanthem with islands of sparing (“white islands in a sea of red”) Clin Inf Dis 36:1004–1005, 1074–1075, 2003; clinical differential diagnosis includes typhoid fever, leptospirosis, meningococcal disease, streptococcal disease, staph, rickettsial disease, malaria, arbovirus (chikungunya, o’nyong-nyong fevers), Kawasaki’s disease

Drug hypersensitivity – acetaminophen Isr J Med Sci 20:145–147, 1984; trimethoprim-sulfa Hautarzt 50:280–283, 1999

Ehrlichiosis

Eccrine squamous syringometaplasia secondary to chemotherapy AD 133:873–878, 1997

Erysipelas – chronic, recurrent

Enterovirus 71 NEJM 341:929–935, 1999

Etoposide – extravasation; edematous bullous red hand Ped Derm 29:264–269, 2012

Erysipeloid – Erysipelothrix insidiosa (rhusiopathiae) – seal finger, blubber finger AD 130:1311–1316, 1994; Clin Microbiol Rev 2:354–359, 1989; JAAD 9:116–123, 1983

Itraconazole AD 130:260–261, 1994

Filariasis – Wuchereria bancrofti

Vancomycin-induced linear IgA disease JAAD 34:890–891, 1996

Herpes simplex virus AD 135:1125–1126, 1999

EXOGENOUS AGENTS

Human herpesvirus 8 – relapsing inflammatory syndrome; fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, exanthem of face, hands, wrists, and elbows NEJM 353:156–163, 2005

Intravenous infiltration with compartment syndrome AD 140:798– 800, 2004 Lionfish sting Cutis 102:232–234, 2018 Parenteral nutrition – extravasation of parenteral nutrition in pre-term or low birth weight infants; edema and compartment syndromes; necrosis, acral necrosis, anonychia Ped Derm 32:830–835, 2015

INFECTIONS AND INFESTATIONS African trypanosomiasis AD 131:1178–1182, 1995 AIDS – AIDS-associated Kawasaki-like syndromes Clin Inf Dis 32:1628–1634, 2001 Anthrax – Bacillus anthracis; malignant pustule; painless ulcer with vesicular lesions; face, neck, hands, fingers, arms, foot, knee; starts as painless erythema evolving into papule then into multiple vesicles or bulla on red base; then ulcer with hemorrhagic crust (eschar) with edema and erythema with small vesicles; edema of surrounding skin; takes six weeks to heal; edema of eyelids, lips, perioral area; slaughtering or milking of ill cows, sheep, or goats; handling of raw meat Ped Derm 27:600–606, 2010; Ped Derm 18:456–457, 2001; Br J Opthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981 Arthropod bite – hypersensitivity to mosquito bites with intense erythema and edema AD 139:1601–1607 Bee sting reaction – personal observation Buruli ulcer – diffuse erythema, edema, and necrosis of dorsal hand JAMA Derm 130:669–671, 2014 Cat scratch disease Centipede bite (Scolopendra subspinipes) AD 146:807–808, 2010 Chromomycosis Dengue fever (Flavivirus) – palmar erythema and edema; morbilliform or scarlatiniform eruption (classic dengue fever) – initially (first 24 hours) flushing of face, neck, and chest; morbilliform or macular eruption with white islands of sparing in a sea of red and petechiae; acral and/or periorbital edema, petechial mucosae, headache, fever, retroorbital pain, arthralgia, myalgia, leukopenia; absence of sore throat and cough; conjunctival hemorrhages, abdominal pain; platelet count under 240,000; incubation period 3–14 days; Aedes aegypti/A. albopictus Dermatol Clinics 29:33–38, 2011; Am J trop Med Hyg 82:922, 2010; JAAD 58:308–316, 2008; JAAD 46:430– 433, 2002; Dermatol Clinics 17:29–40, 1999; Inf Dis Clin NA 8:107,

Leprosy – reversal reaction in leprosy – periarticular erythema and edema of hand with edema of red plaques of trunk; existing lesions become red and tumid with edema of the hands, neuritis, sensory and motor loss with foot drop, wrist drop, facial palsy, lagophthalmos, keratitis and blindness JAAD 83:17–30, 2020; JAAD 71:795– 803, 2014; type 1 leprosy reactions – edema of hands, feet, face; mountain range-like swelling of prior lesions BJD 167:29035, 2012; type 2 lepra reaction Int J Lepr Other Mycobact Dis 1986; lepromatous; type 1 or type 2 reaction in borderline; lepromatous; type 1 or type 2 reaction in borderline; type 1 reaction demonstrates reappearance of resolved lesions, acute peripheral neuritis, edema of hands, feet, and face JAAD 57:914–917, 2007; JAAD 51:417– 426, 2004; erythema nodosum leprosum – edema of hands and feet BJD 144:175–181, 2001 Loiasis – Calabar swellings; temporary of arm and hand, and elsewhere; angioedema Necrotizing fasciitis – Group A Streptococcus pyogenes NEJM 360:281–290, 2009 Parvovirus B19 Diagn Microbiol Infect Dis 36:209–210, 2000; papular and purpuric gloves and socks syndrome; painful and pruritic symmetric swelling of hands and feet JAAD 48:941–944, 2003 Pasteurella multocida – cellulitis with ulceration with hemorrhagic purulent discharge with sinus tracts Medicine 63:133–144, 1984 Rat bite fever (Streptobacillus moniliformis) – fever, arthritis, exanthema; papules and papulopustules of face and hand; hand and foot swellings Ped Derm 29:767–768, 2012 Salmonella osteomyelitis and the hand-foot syndrome J Pediatr Orthop 12:534–538, 1992 Seal finger – painful, swollen red finger; synovitis J Rheumatol 13:647–648, 1986 Spider bites Rev Ins Med Trop Sao Paolo 2000 Toxic shock syndrome, either streptococcal or staphylococcal – widespread macular erythema, scarlatiniform, and papulopustular eruptions; occasional vesicles and bullae; edema of hands and feet; mucosal erythema; second week morbilliform or urticarial eruption occurs with desquamation at 10–21 days Clin Inf Dis 32:1470–1479, 2001; JAAD 39:383–398, 1998; Rev Infect Dis 11 (Suppl 1):S1–7, 1989; JAAD 8:343–347, 1983 Trypanosomiasis – African; edema of face, hands, feet with transient red macular, morbilliform, petechial or urticarial dermatitis; circinate, annular of trunk

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INFILTRATIVE DISEASES Scleromyxedema Cutis 85:137–140, 2010

INFLAMMATORY DISORDERS

Lymphoma – cutaneous T-cell lymphoma with large cell transformation – personal observation Pancoast tumor (superior sulcus tumor) – unilateral J Thoracic Dis Suppl 4:S342–358, 2013 Retroperitoneal leiomyoma Canadian J Surg 25:79–80, 1982

Ankylosing spondylitis Eosinophilic fasciitis – personal observation

PARANEOPLASTIC DISEASES

Kawasaki’s disease – erythema and edema of hands and feet Ped Derm 36:274–282, 2019; JAAD 69:501–510, 2013; Am J Cardiol 83:337–339, 1999; JAAD 39:383–398, 1998

Acrokeratosis paraneoplastica – hand edema, desquamation of hands; hyperkeratotic and lichenified plaques of hands; vesicles and bullae of hands JAMA Derm 151:677–678, 2015

Polymyalgia rheumatic

Paraneoplastic CREST syndrome – personal observation

Relapsing polychondritis

Paraneoplastic remitting seronegative symmetrical synovitis – adenocarcinoma Clin Exp Rheumatol 17:741–744, 1999

Remitting seronegative symmetrical synovitis with pitting edema of hands (RS3PE); malignancy BJD 174:1420–1421, 2016; AD 148:1217–1218, 2012; JAMA 254:2763–2767, 1985 Urticaria multiforme – wheals, fever, arcuate, annular, polycyclic lesions; ecchymotic center or central pallor; edema of hands and feet; aged 4 months to 4 years NEJM 315:470, 2016; Cutis 89:260:262–264, 2012; Pediatrics 119:e1177–1183, 2007

METABOLIC DISEASES Acromegaly – soft tissue edema of hands and feet; personal observation Fabry’s disease – edema of hands, arms, eyelids AD 140:1526– 1527, 2004 Glomerulonephritis Pediatr Med Chir 14:425–431, 1992 Gout Hypoalbuminemia of any cause Hypothyroidism – puffy edema of hands JAAD 26:885–902, 1992 Kwashiorkor

PHOTODERMATOSES Phytophotodermatitis – personal observation

PRIMARY CUTANEOUS DISEASES Acquired cutis laxa – acral Autosomal recessive congenital ichthyosis – ichthyosis, erythroderma, collodion baby, contractures of large joints, palmoplantar hyperlinearity, edema of fingers; CYP4F22 mutation BJD 176:1068– 1073m 2017 Collodion baby (lamellar desquamation of the newborn) – sausage shaped swelling of digits Constriction bands JAAD 15:296–297, 1986 Dyshidrosis with secondary infection – lymphedema of hand BJD 161:177–180, 2009

Nephrogenic fibrosing dermopathy

Episodic angioedema with eosinophilia – swollen feet BJD 159:738–740, 2008; NEJM 310:1621–1626, 2008

Porphyria – erythropoietic protoporphyria BJD 155:574–581, 2006; Eur J Pediatr 159:719–725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751–766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976; congenital erythropoietic porphyria BJD 148:160–164, 2003

Harlequin fetus (ichthyosis congenital fetalis) – severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis – edema of hands and feet encased in hard casts JAAD 212:335– 339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982

Pregnancy Arthritis Rheumatism 39:1761–1762, 1996

Psoriatic arthritis – lymphedema of hand/forearms BJD 143:1297– 1301, 2000; lymphedema of arms Semin Arthr Rheum 22:350–356, 1993

Sickle cell disease – hand-foot syndrome; edema of hands and feet due to underlying bone infarction Clin Pediatr 20:311–317, 1981 Thyroid acropachy – digital clubbing, periosteal reactions, edema of the hands and feet Ped Derm 35:3371–374, 2018JAAD 48:641– 659, 2003

Scleredema Scleromyxedema – personal observation Urticaria multiforme – annular, serpiginous, urticarial lesions; edema of hands, feet, face NEJM 375:470, 2016

NEOPLASTIC DISEASES Chondrosarcoma of the hand Eur J Radiol 84:2004–2012, 2015

PSYCHOCUTANEOUS DISEASES

Cancer, advanced

Factitial edema of hand JAAD 13:988, 1985

Kaposi’s sarcoma JAAD 38:143–175, 1998; Int J Derm 36:735–740, 1997; Dermatology 190:324–326, 1995

Gardner-Diamond syndrome – edema of hands and feet; purpura and ecchymoses J Clin Aesthet Dermatol 12:44–46, 2019

Epstein-Barr virus-associated hydroa vacciniforme-like cutaneous lymphoma; variant of extranodal NK/T cell lymphoma, nasal type/ CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of hands, subcutaneous nodules; systemic manifestations; occurs on both sun–exposed and non-sun-exposed skin Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998

SYNDROMES Aicardi-Goutieres syndrome – autosomal recessive; chilblains, acrocyanosis, puffy hands and feet; blueberry muffin baby; intracranial calcification with enlarged ventricles; progressive encephalopathy; increased cerebrospinal fluid interferon alpha and

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lymphocytosis Ped Derm 26:432–435, 2009; Am J Hum Genet 81:713–725, 2007; Ann Neurol 44:900–907, 1998 Behcet’s syndrome – superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of neck with neck vein distension, upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008 Cardio-facio-cutaneous syndrome – autosomal dominant, xerosis/ ichthyosis, eczematous dermatitis, alopecia, growth failure, hyperkeratotic papules, ulerythema ophryogenes (decreased or absent eyebrows), seborrheic dermatitis, CALMs, nevi, hemangiomas, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly scalp hair and sparse eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies with macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of supraorbital ridges, short nose with depressed nasal bridge, high arched palate, low set posteriorly rotated ears with prominent helices, cardiac defects; gain of function sporadic missense mutations in BRAF, KRAS, MEK1, or MEK2, MAP2K1/MAP2K2 BJD 163:881–884, 2010; Ped Derm 27:274–278, 2010; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992

Olmsted syndrome Int J Derm 36:359–360, 1997 Palmar fasciitis and polyarthritis syndrome – painful swelling over palmar PIP joints – indurated palmar skin; flexion contractures; may be paraneoplastic (transitional cell carcinoma of the bladder) JAAD 64:1159–1163, 2011; Ann Int Med 96:424–431, 1982 Papular-purpuric “gloves and socks” syndrome – erythema and edema of hands and feet as initial signs BJD 151:201–206, 2004; JAAD 41:793–796, 1999; JAAD 37:673–705, 1997 POEMS syndrome – personal observation Reflex sympathetic dystrophy (complex regional pain syndrome) – erythema and edema; muscle wasting JAMA Derm 150:640–642, 2014; Cutis 68:179–182, 2001; JAAD 35:843–845, 1996; Arch Neurol 44:555–561, 1987 RS3PE remitting seronegative symmetrical synovitis with pitting edema Clin Exp Rheumatol Jul-Aug:18, 2000 Secretan's syndrome (l’-oedeme bleu) Seronegative symmetrical synovitis and pitting edema syndrome BJD 174:1420–1422, 2016 Sly syndrome Turner's syndrome – congenital lymphedema of hands; resolves in 3 years JAAD 74:231–244, 2016; JAAD 46:161–183, 2002

Carpal tunnel syndrome BJD 150:166–167, 2004

Translocation of chromosome 13 Humangenetik 28:93–96, 1975

Chromosome 18p syndrome Ann Genet 31:60–64, 1988

Yellow nail syndrome BJD 156:1230–1234, 2007; BJD 134:307– 312, 1996

Costello syndrome JAAD 32:914–7, 1995 Eosinophilic fasciitis (Shulman's syndrome) BJD 100:381–384, 1979 Fibroblastic rheumatism Ped Derm 19:532–535, 2002 Hereditary angioedema – autosomal dominant; prodrome of erythema marginatum (annular urticarial eruption); facial, lip, eyelid, tongue, and hand edema JAAD 65:843–850, 2011; Monatsh Prakt Derm 1:129–131, 1882; Edinb Med J 22:513–526, 1876 Hereditary fibrosing poikiloderma with tendon contracture, myopathy, fibrosis, and alopecia; FAM IIIB mutation – mimics RothmundThomson syndrome Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016   Poikiloderma of cheeks  Alopecia   Myopathy – fatty infiltration of muscles  Hypohidrosis   Lymphedema of hands and legs   Exocrine pancreatic insufficiency   Extraocular muscle weakness   Tendon contractures   Pulmonary fibrosis

TOXINS Acrodynia (mercury poisoning) – profuse sweating; red edematous hands and feet, hypertension, severe periumbilical pain, irritability Ped Derm 29:199–201, 2012; Pediatr Nephrol 22:903–906, 2009; Ped Derm 21:254–259, 2004; Arch Dis Child 62:293–295, 1987; Lancet 29:829–830, 1948; Arch Dermatol Syphilol 26:215–237, 1932; Rev Med Fr 3:51–74, 1830 Eosinophilic myalgia syndrome (L-tryptophan)

TRAUMA Burns Deprivation of hands and feet Arch Dis Child 60:976–977, 1985 Drug abuse (IVDA) – lymphedema of the hand due to skin popping (“puffy hand syndrome”) JAAD 69:135–142, 2013; AD 142:1084– 1085, 2006; BJD 150:1–10, 2004 Extravasation of medications – hydantoin (Dilantin)

Hurler’s syndrome – personal observation

Mountain sickness, acute Respir Physiol 46:383–390, 1981

Neu-Laxova syndrome – variable presentation; mild scaling to harlequin ichthyosis appearance; ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema and mildly edematous feet and hands, absent nails; microcephaly, intrauterine growth retardation, limb contractures, low set ears, sloping forehead, short neck; small genitalia, eyelid and lip closures, syndactyly, cleft lip and palate, micrognathia; autosomal recessive; uniformly fatal Ped Derm 20:25–27, 78–80, 2003; Curr Prob Derm 14:71–116, 2002; Clin Dysmorphol 6:323–328, 1997; Am J Med Genet 35:55–59, 1990

Surgical scar

Neurofibromatosis – hemihypertrophy Nevo syndrome Am J Med Genet Feb 1998 Nodules, eosinophilia, rheumatism, dermatitis, and swelling Clin Exp Allergy 23:571–580, 1993 Noonan's syndrome – transient lymphedema of hands and feet

Trauma – traumatic palmar and plantar plaques of childhood Ped Derm 12:72, 1995

VASCULAR DISEASES Acute hemorrhagic edema of infancy (Finkelstein’s disease) Ped Derm 36:274–282, 2019; JAAD 59:684–695, 2008; Ped Int 45:697–700, 2003; Cutis 68:127–129, 2001; J Dermatol 28:279– 281, 2001; Cutis 61:283–284, 1998; AD 130:1055–1060, 1994; JAMA 61:18–19, 1913 Arteriovenous fistulae – venous hypertension Axillary or subclavian vein thrombosis (Paget-Schroetter syndrome) – personal observation

Edema, Head Capillary leak syndrome BJD 150:150–152, 2004 Eosinophilic vasculitis syndrome – palmar edema BJD 14:901–902, 2003; Semin Derm 14:106–110, 1995 Henoch-Schonlein purpura Ped Derm 15:426–428, 1998 Idiopathic systemic capillary leak syndrome – skin-colored or red papules of face, neck, abdomen, upper back, elbows, and hands; purpuric macules of lateral fingers, infiltrative edema of hands with sclerodermoid appearance, livedo reticularis of lower extremities; photodistributed eruption of face, neck, and arms Dermatology 209:291–295, 2004 Intestinal lymphangiectasia

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Cushing’s syndrome due to Chinese herbal tea and creams BJD 169:1367–1369, 2013 Hydantoin (Dilantin) Irbesartan J Drugs Dermatol 3:329–303, 2002 Imatinib (signal transduction inhibitor) – edema of face, forearms, ankles JAAD 48:201–206, 2003 Oral contraceptives JAMA 201:982, 1967

INFECTIONS AND INFESTATIONS

Klippel-Trenaunay syndrome

Anthrax

Lymphangioma, diffuse

Bee stings, multiple Plast Reconstr Surg 110:1192–1193, 2002

Lymphangiosarcoma

Buruli ulcer (Mycobacterium ulcerans) Am J Trop Med Hyg 77:1099, 2007

Lymphangitis, infectious (post-cellulitis, erysipelas) Lymphatic obstruction following axillary lymph node dissection Lymphedema – congenital (Milroy’s disease), praecox, tarda Cutis 38:105, 1986; lymphedema secondary to intestinal lymphangiectasia; due to mediastinal lymphoma – personal observation

Cat scratch disease Dermatophytid – angioedema Ped Derm 32:635–640, 2015 Gnathostomiasis Ned Tijdschr Geneeskd 17:322–3225, 2001 Hantavirus Epidemiol Infect 111:171–175, 1993

Polyarteritis nodosa

Katayama disease (Schistosoma japonicum)

Superior vena cava syndrome – personal observation

Lassa fever – capillary leak syndrome with severe swelling of head and neck, oral ulcers, tonsillar patches JAAD 65:1213– 1218, 2011

Thrombosis of axillary vein Vasculitis, urticarial – painful purpuric plaques on edematous hands AD 141:1457–1462, 2005 Recurrent cutaneous eosinophilic vasculitis – palmar edema BJD 149:901–902, 2003 Congenital Volkmann ischemic contracture (neonatal compartment syndrome) – upper extremity circumferential contracture from wrist to elbow; necrosis, cyanosis, edema, eschar, bullae, purpura; irregular border with central white ischemic tissue with formation of bullae, edema, or spotted bluish color with necrosis, a reticulated eschar or whorled pattern with contracture of arm; differentiate from necrotizing fasciitis, congenital varicella, neonatal gangrene, aplasia cutis congenita, amniotic band syndrome, subcutaneous fat necrosis, epidermolysis bullosa BJD 150:357–363, 2004

EDEMA, HEAD

Leprosy – reversal reaction with unilateral facial swelling ORL J Otorhinolaryngol Relt Spec 64:281–283, 2002 Mansonelliasis (filariasis) (M. ozzardi) – biting midges or black flies; angioedema, chronic pruritus with hyperpigmentation, papular eruption JAAD 75:19–30, 2016 Mucormycosis, rhinocerebral – caused be Conidiobolus coronatus Mycopathologia 115:1–8, 1991 Mycobacterium tuberculosis – lupus vulgaris Necrotizing fasciitis Ann Chir Plast Esthet 50:233–236, 2005 Pott's puffy tumor – periosteal osteomyelitis AD 121:548–549, 1985 Rattlesnake envenomation of the face Ped Emerg Care 21:173– 176, 2005 Spider bite (cutaneous loxoscelism) Bol Chil Parasitol 53:78–83, 1998 Tick bite – edema of scalp

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

INFLAMMATORY DISORDERS

Allergic contact dermatitis

Kimura’s disease Kulak Burun Bogaz Ihtis Derg 12:139–143, 2004

Angioedema, including scalp swelling J Pediatr 129:163–165, 1996; hereditary angioneurotic edema

Lymphocytoma cutis

Dermatomyositis – malignant edema; generalized total body edema JAAD 66:144–147, 2012

Sarcoid – Heerfordt’s syndrome NEJM 369:458, 2013 Sialadenitis – acute sialadenitis of parotid and submandibular glands with unilateral facial swelling Ned Tijdschr Geneeskd 149:877, 2005

CONGENITAL LESIONS Cephalohematoma – rupture of diploic veins during prolonged delivery with subperiosteal hemorrhage; unilateral ECMO (extracorporeal membrane oxygenation) – erythema, edema, crusted ulcerations, scarring alopecia Congenital lymphedema

DRUGS ACE inhibitors

METABOLIC DISEASES Acromegaly Dermatol Online J Aug 15, 2017; Clin Dermatol 24:256–259, 2006 Congenital erythropoietic porphyria JAAD 34:924–927, 1996 Cushing’s syndrome Hypoalbuminemia of any cause Hypothyroidism (myxedema) Kwashiorkor – plump appearance of face

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Nephrogenic systemic fibrosis with superior vena cava syndrome J Drugs in Dermatol 13:615–618, 2014

to extravasated blood or serum; venous congestion; resolves within a few days Ped Derm 23:533–536, 2006

Nephrotic syndrome

Hematoma – subgaleal hematoma – scalp edema J Trauma 28:1681–1683, 1988; dental crown preparation J Mich Dent Assoc 95:54–56, 2013

Paroxysmal nocturnal hemoglobinuria – petechiae, ecchymoses, red plaques which become hemorrhagic bullae with necrosis; lesions occur on scalp, legs, abdomen, chest, nose, and ears; acute edema of head and face; deficiency of enzymes – decay-accelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL); somatic mutation of PIG-A gene of totipotent hematopoietic stem cells JAAD 53:1090–1092, 2005; AD 138:831–836, 2002 Sickle cell disease Dial Dis 7:306–309, 2001

NEOPLASTIC DISEASES Angiosarcoma Cancer 59:1046–1057, 1987 Kaposi’s sarcoma – lymphadenopathic and lymphedematous Kaposi's sarcoma

Prone posturing in acute respiratory distress syndrome; Covid-19 pneumonia Arch Acad Emerg Med 8:e48, 2020; Am J Resp Crit Care Med 165:1359–1363, 2002 Subcutaneous emphysema – facial edema NEJM 342:176, 2000; AD 134:557–559, 1998 Sunburn – scalp edema Turk J Pediatr 54:540–542, 2012 Trauma, including fatal massive edema of the head and neck due to scalp laceration J Oral Surg 35:215–218, 1977

VASCULAR DISEASES Angiosarcoma of the face and scalp Cancer 59:1046–1057, 1987

Lymphoma – retro-orbital B-cell lymphoma JAAD 42:872–874, 2000

Eosinophilic vasculitis syndrome Semin Dermatol 14:106–110, 1995

Merkel cell carcinoma AD 124:21, 1988

Giant cell arteritis Rev Rheum Engl Ed 63:145–147, 1996

Subcutaneous panniculitic T-cell lymphoma

Hemangioma – diffuse hemangioma AD 139:869–875, 2003 Henoch-Schonlein purpura – scalp and facial edema Ped Derm 9:311, 1992

PARANEOPLASTIC DISORDERS Capillary leak syndrome Presse Med 29:1279–1281, 2000

PRIMARY CUTANEOUS DISEASES Lipedematous alopecia – scalp edema J Cutan Pathol 27:49–53, 2000 Scleredema – edema of scalp, upper face, orbits J Pediatr 101:960– 963, 1982

Idiopathic bilateral external jugular vein thrombosis Angiology 52:69–71, 2001 Lymphatic malformation Superior vena cava syndrome – cancer, Behcet’s disease, hypercoagulable states; iatrogenic – central catheterization and pacemaker implantation BJD 159:555–560, 2008; Clin Exp Derm 25:198–200, 2000; Int J Dermatol 39:396–397, 2000; Clin Rheumatol 14:526–530, 1995 Vascular malformation

Solid facial edema Eur J Dermatol13:503–504, 2003

EDEMA, LEGS SYNDROMES Behcet's syndrome JAAD 26:863–864, 1992; superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of neck with neck vein distension, upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008 Hereditary angioneurotic edema – mutation in SERPING1 or Factor XII BJD 173:1102–1104, 2015 Mutations in PHF6 associated with Borjeson-Forssman-Lehman syndrome Nat Genet 52:661–665, 2002 Neu-Laxova syndrome – ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema, absent nails; autosomal recessive; edema may be restricted to the scalp Am J Med Genet 35:55–59, 1990 Sphenopalatine syndrome

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – complicating venous stasis Angioedema Am J Med 113:580–586, 2002 Autoinflammatory syndrome with lymphedema (AISLE) – fever and urticarial, progressive edema of scrotum and legs; mutation in MyoD family inhibitor domain-containing protein Ped Derm 33:602–614, 2016 GATA 2 deficiency – multiple warts, multiple soft tissue infections, lower leg lymphedema, sensorineural deafness, squamous cell carcinomas, panniculitis, erythema nodosum, Sweet’s syndrome; GATA 2 – zinc finger transcription factor that regulates vascular and lymphatic development, and hematopoietic maturation JAAD 71:577–580, 2014 Lupus erythematosus, systemic – pitting edema of legs Rheumatol Int 18:159–160, 1999; Br J Rheumatol 37:104–105, 1998

Turner's syndrome – congenital lymphedema; lymphedema of scalp; resolves in 3 years

Morphea – linear morphea Clin Exp Dermatol 24:467–468, 1999; JAAD 38:366–368, 1998; BJD 134:594–595, 1996; generalized morphea – non-­pitting edema of trunk and extremities Ped Derm 27:58–61, 2010

TRAUMA

Polymyalgia rheumatica – distal extremity swelling, pitting edema Arthritis Rheum 39:73–80, 1996

Caput succedaneum – after prolonged labor – pressure on parietal and occipital scalp from engagement with cervix, uterus, and vaginal wall during delivery; diffuse edematous swelling of scalp due

Serum sickness Am J Med 113:580–586, 2002 Urticaria Am J Med 113:580–586, 2002

Edema, Legs

DEGENERATIVE DISEASES Paralysis of any cause

DRUG REACTIONS Acyclovir therapy – peripheral edema JAAD 18:1142–1143, 1988 All-trans-retinoic acid – retinoic acid syndrome; fever, respiratory distress, weight gain, leg edema, pleural effusions, renal failure, pericardial effusions, hypotension, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum JAAD 56:690—693, 2007; Leuk Lymphoma 44:547–548, 2003 Antidepressants Am J Med 113:580–586, 2002 Anti-hypertensives Am J Med 113:580–586, 2002 Beta blockers Am J Med 113:580–586, 2002 Calcium channel blockers Am J Med 113:580–586, 2002 Clofazimine – pedal edema Int J Lepr Other Mycobact Dis 61:636, 1993 Clonidine Am J Med 113:580–586, 2002 Corticosteroids Am J Med 113:580–586, 2002

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Selective cyclooxygenase-2 inhibitors Am J Med 113:580–586, 2002 Sirolimus – unilateral or bilateral lower extremity lymphedema BJD 160:1322–1326, 2009 Testosterone Am J Med 113:580–586, 2002 Troglitazone Am J Med 113:580–586, 2002

EXOGENOUS AGENTS Cocaine abuse – deep vein thrombosis, urticaria and urticarial vasculitis Clin Exp Dermatol 45:630–632, 2020 Drug abuse – edema secondary to skin popping, infection, scarring L-tryptophan-induced eosinophilic fasciitis Podoconiosis (mossy foot) – lymphedema due to silica dust (microparticles) (irritant clay soils of volcanic origin) in soil acquired by walking barefoot in tropical volcanic highland areas; multilobulated hyperkeratotic nodules of feet; cobblestoned; bare feet exposed to red clay from alkaline volcanic rock; lymphedema of feet; red volcanic soil of upland Ethiopia BJD 168:550–554, 2013; JAAD 65:214–215, 2011;

Diazoxide Am J Med 113:580–586, 2002

non-filiarial lymphedema BJD 162:998–1003, 2010; BJD 159:903– 906, 2008; JAAD 59:324–331, 2008

Docetaxel-induced scleroderma BJD 156:363–367, 2007

Post-Greenfield or other inferior vena cava filter

G-CSF – recombinant human GCSF; livedo reticularis, edema, with thrombotic and necrotizing panniculitis BJD 142:834–836, 2000 Gemcitabine – edema of legs with subsequent sclerodermoid changes JAAD 51:S73–76, 2004

INFECTIONS AND INFESTATIONS

Gene transfer of naked DNA encoding vascular endothelial growth factor Ann Int Med 132:880–884, 2000

African tick bite fever – Rickettsia africae; Amblyomma hebraeum or A. variegatum; petechiae, purpura, fever, leg edema AD 148:247– 252, 2012

Guanethidine Am J Med 113:580–586, 2002

Cat scratch fever

Hormones (estrogens, progesterones) Am J Med 113:580–586, 2002

Cellulitis, recurrent

Hydralazine Am J Med 113:580–586, 2002

Cryptococcosis – edematous erythema with subcutaneous plaques of legs JAMA 309:1632–1633, 2013

Imatinib/dasatinib/nilotinib (tyrosine kinase inhibitors) – edema; edema of the extremities JAAD 71:217–227, 2014 Insulin edema – generalized, 1–3 days after ketoacidosis South Med J 2:445, 1979 Interleukin 2 Am J Med 113:580–586, 2002 Methyldopa Am J Med 113:580–586, 2002 Methysergide – retroperitoneal fibrosis Minoxidil Am J Med 113:580–586, 2002 Monoamine oxidase inhibitor anti-depressants Am J Med 113:580– 586, 2002 Nifedipine (calcium channel blockers) Nonselective cyclooxygenase inhibitors Am J Med 113:580–586, 2002 Non-steroidal anti-inflammatory agents Am J Med 113:580–586, 2002 Paclitaxel-induced scleroderma BJD 156:363–367, 2007 Phenylbutazone Am J Med 113:580–586, 2002 Pioglitazone Am J Med 113:580–586, 2002 Pramipexole – peripheral edema Arch Neurol 57:729–732, 2000 Rapamycin BJD 174:933–934, 2016; BJD 160:1322–1326, 2009 Reserpine Am J Med 113:580–586, 2002 Rosiglitazone Am J Med 113:580–586, 2002

Chromomycosis

Dermatophyte infection Ebola virus Erysipelas – chronic, recurrent Filariasis – Wuchereria bancrofti, Brugia malayi, Brugia timori; Anopheles mosquito vector – first sign is edema, pain, and erythema of arms, legs, or scrotum; chronically lower leg edema and elephantiasis develop J Drugs in Dermatol 13:210–215, 2014; JAMA 310:1551, 2013; NEJM 369:745–753, 2013; Dermatol Clin 7:313–321, 1989 Kala azar (visceral leishmaniasis) – Leishmania donovani – pedal edema; primary ulcer; hyperpigmented skin of face, hands, feet abdomen Klebsiella pneumonia – necrotizing fasciitis; massive edema, erythema, necrosis of thigh Clin Inf Dis 56:1457,1505–1506, 2013 Leprosy – lepromatous leprosy – edema of legs and ankles Lymphogranuloma venereum – genital lymphedema leading to vulvar elephantiasis or “saxophone penis”; inguinal adenitis with abscess formation and draining chronic sinus tracts; rectal syndrome in women with pelvic adenopathy, periproctitis with rectal stricture and fistulae; esthiomene – scarring and fistulae of the buttocks and thighs with elephantiasic lymphedema of the vulva; lymphatics may develop abscesses which drain and form ulcers Int J Dermatol 15:26–33, 1976

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Meningococcemia – cellulitis with edema, erythema, and pain Clin Inf Dis 21:1023–1025, 1995 Mycobacterium tuberculosis – lupus vulgaris; tuberculous node infection Br J Surg 51:101–110, 1964 Onchocerciasis – edema of leg, face, arm, and scrotum JAAD 73:929–944, 2015; JAAD 45:435–437, 2001; Int J Derm 22:182, 1983 Pyomyositis – non-erythematous calf edema; Staphylococcus aureus, streptococcal species; Cryptococcus neoformans Clin Inf Dis 32:1104–1107, 2001

as presenting sign Am J Med Sci 318:413–414, 1999; unilateral leg edema JAAD 30:498–500, 1994; AD 109:543–544, 1974

METABOLIC DISEASES Acromegaly Beriberi (Vitamin B1, thiamine deficiency) – anorexia, weakness, constipation, polyneuritis, cardiac failure with edema, muscle wasting Am J Med 113:580–586, 2002; JAAD 21:15–18, 1989

Rattlesnake bite Pediatr Emerg Care 10:30–33, 1994

Carcinoid syndrome – dependent edema due to low serum proteins BJD 152:71–75, 2005

Rocky Mountain spotted fever – especially in children MMWR 65:1–44, May 13, 2016

Cirrhosis, liver failure Am J Med 113:580–586, 2002

Schistosomiasis – Katayama fever – edema of the legs JAAD 73:929–944, 2015 Toxocariasis – lymphedema as presenting sign Infection 23:389– 390, 1995 Trichinosis Presse Med 24:1317, 1995 Trypanosomiasis, African (Trypanosoma brucei rhodesiense) – joint pain during parasitemia; fever, headache, malaise; 3–10 days after appearance of chancre; ascites and peripheral edema; facial edema and edema of hands JAAD 60:897–925, 2009

Congestive heart failure – ankle edema JAAD 59:324–331, 2008 Cryofibrinogenemia – edema and bullae of feet Am J Med 116:332– 337, 2004 Fabry’s disease – lymphedema BJD 157:331–337, 2007 Fluid retention – ankle edema Hypoalbuminemia of any cause JAAD 59:324–331, 2008 Kwashiorkor JAAD 52:S69–72, 2005; Cutis 67:321–327, 2001 Liver cyst – inferior vena cava compression Acta Med Scand 205:541–542, 1979 Malabsorption Am J Med 113:580–586, 2002

INFILTRATIVE DISEASES Pretibial myxedema – occurs in 1–10% of patients with Grave's disease; often associated with exophthalmos; solid non-pitting edema of shins and feet; elephantiasic form with edema and nodule formation NEJM 372:764, 2015; Cutis 79:219–224, 2007; Lancet 341:403–404, 1993; JAAD 14:1–18,1986; AD 117:250–251, 1981; elephantiasic pretibial myxedema JAAD 46:723–726, 2002

Myxedema – edema of legs and feet NEJM 372:764, 2015; Am J Med 113:580–586, 2002 Obesity, massive JAAD 59:324–331, 2008; NEJM 327:1927, 1993 Preeclampsia Am J Med 113:580–586, 2002 Pregnancy JAAD 59:324–331, 2008; Am J Med 113:580–586, 2002; Premenstrual edema Am J Med 113:580–586, 2002; J Am Board Fam Med 19:148–160, 2006 Pretibial myxedema – personal observation

INFLAMMATORY DISEASES Atypical lymphocytic lobular panniculitis (T cell dyscrasia) – spontaneously resolves; red plaques and nodules of arms and legs with associated edema; identical presentation as subcutaneous panniculitis-like T-cell lymphoma with hemophagocytosis JAAD 61:875–881, 2009; J Cutan Pathol 31:300–306, 2004

Prolidase deficiency – autosomal recessive; skin spongy and fragile with annular pitting and scarring; leg ulcers; photosensitivity, telangiectasia, purpura, premature graying, lymphedema Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987 Protein-losing enteropathy JAAD 59:324–331, 2008

Bursitis – iliopectineal – iliofemoral vein compression J Vasc Surg 13:725–727, 1991; iliopsoas J Rheumatol 13:197–200, 1986

Pulmonary hypertension JAAD 59:324–331, 2008

Erythema induratum (Whitfield) – nodules with edematous ankles

Renal failure Am J Med 113:580–586, 2002; nephrotic syndrome

Inflammatory lymphedema and inflammatory vasculitis – red feet and edema of legs in Air Force basic trainees JAMA Derm 151:395–400, 2015

Scurvy – woody edema of legs BJD 80:625–628, 1968

Rhabdomyolysis – acute swollen legs BMJ 309:1361–1362, 1994

Spherocytosis – pseudoerysipelas due to recurrent hemolysis JAAD 51:1019–1023, 2004

Muscle infarction Am J Kidney Dis 35:1212–1216, 2000; diabetic muscle infarction; exquisitely tender non-indurated swelling of thigh AD 143:1456–1457, 2007; NEJM 337:839–845, 1997;

NEOPLASTIC DISEASES

Diabetalogica 1:39–42, 1965

Abdominal or pelvic masses

Pancreatic pseudocyst – compression of inferior vena cava Mayo Clin Proc 67:1085–1088, 1992

Aggressive fibromatosis (desmoids tumor) – edema of ankle JAAD 59:S7–9, 2008

Panniculitis

Baker’s cyst, ruptured – swelling and pain of calf

Retractile mesenteritis (IgG4 disease) – edema of abdominal wall, lower extremities, genitalia

Eccrine porocarcinoma (malignant eccrine poroma) BJD 150:607– 609, 2004;

RS3PE – remitting seronegative symmetrical synovitis with pitting edema; JAMA 254:2763, 1985; paraneoplastic Clin Exp Rheum 17:741–744, 1999

Kaposi’s sarcoma BJD 173:1501–1504, 2015; JAAD 59:179–206, 2008; Dermatol Clin 24:509–520, 2006; JAAD 38:143–175, 1998; Int J Derm 36:735–740, 1997; Dermatology 190:324–326, 1995; hyperkeratotic Kaposi’s sarcoma in AIDS with massive lymphedema BJD 142:501–505, 2000

Sarcoidosis – JAAD 30:498, 1993; J R Soc Med 78:260–261, 1985; unilateral leg edema JAAD 44:725–743, 2001; bilateral leg edema

Edema, Legs Kaposi’s sarcoma – edema of legs and feet Lipomas – pelvic lipomatosis Jpn J Med 30:559–563, 1991 Liposarcoma, retroperitoneal Vasa 19:334–335, 1990 Lymphangiosarcoma (Stewart-Treves tumor) – red-brown or ecchymotic patch, nodules, plaques in lymphedematous limb; edematous arm within violaceous plaque with nodules NEJM 359:950, 2008; Cancer 1:64–81, 1948 Lymphoma – angiotropic lymphoma South Med J 86:1432–1435, 1993; angioimmunoblastic lymphadenopathy (T-cell lymphoma) – edema of arms and legs BJD 144:878–884, 2001; large cell B-cell lymphoma of the leg JAAD 49:223–228, 2003; intravascular B-cell lymphoma – edema of legs; painful gray-brown, red, blue-livid patches, plaques, nodules, with telangiectasia and underlying induration; 40% of patients with intravascular lymphoma present with cutaneous lesions JAAD 61:888–891, 2009; BJD 157:16–25, 2007; subcutaneous panniculitis-like T-cell lymphoma with hemophagocytosis – red plaques and nodules of arms and legs with associated edema of legs JAAD 61:875–881, 2009 Malignant glomus tumor Br Med J 1:484–485, 1972 Metastatic tumor to inguinal lymph node chain Osteochondroma – unilateral edema J Bone Joint Surg Br 69:339– 340, 1987 Waldenstrom’s macroglobulinemia – peripheral edema due to hyperviscosity JAAD 45:S202–206, 2001

PRIMARY CUTANEOUS DISEASES Lipedema – edema of legs, thighs, buttocks, and hips; sparing of feet (“stovepipe legs”); only in women BJD 163:296–301, 2010; BJD 161:980–986, 2009; JAAD 57:S1–3, 2007; JAAD 50:969–972, 2004; Lymphology 34:170–175, 2001; J Cutan Pathol 27:49–53, 2000; Plast Reconstr Surg 94:841–847, 1994; Mayo Clin Proc 15:184–187, 1940 Lipodystrophy – ankle edema Non-episodic angioedema with eosinophilia – erythema, livedo reticularis, edema of legs, urticaria Cutis 93:33–37, 2014 Psoriasis – exfoliative erythroderma Scleredema of Buschke (pseudoscleroderma) – of the thighs BJD 134:1113–1115, 1996

PSYCHOCUTANEOUS DISORDERS Factitial limb edema Ann Hematol 70:57–58, 1995; due to factitial application of tourniquet (elastic band, clothing) (Secretan’s syndrome) Plast Reconstr Surg 65:182–187, 1980

SYNDROMES Bannayan-Zonana- Ruvalcaba syndrome Behcet’s syndrome – superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of neck with neck vein distension, upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008 Cronkhite-Canada syndrome – diarrhea, protein-losing enteropathy, and peripheral edema; atrophic fingernails NEJM 366:463–468, 2012 Distichiasis-lymphedema syndrome – lymphedema of feet and ankles BJD 142:148–152, 2000

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Ectodermal dysplasia and immunodeficiency – lymphedema; NEMO mutation Hum Molec Genet 11:2371–2375, 2002; Pediatrics109:e97, 2002; Nat Genet 27:277–285, 2001; Am J Med Genet 99:172–177, 2001 Gorham-Stout (disappearing bone) disease – lymphatic malformations with monostotic or polystotic osteolysis JAAD 56:S21–25, 2007; J Bone Joint Surg Am 37A:985–1004, 1955; Boston Med Surg J 18:368–369, 1838 Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, hirsutism, bilateral single palmar crease, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006 Hereditary fibrosing poikiloderma with tendon contracture, myopathy, fibrosis, and alopecia; FAM IIIB mutation – mimics RothmundThomson syndrome Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016   Poikiloderma of cheeks  Alopecia   Myopathy – fatty infiltration of muscles  Hypohidrosis   Lymphedema of hands and legs   Exocrine pancreatic insufficiency   Extraocular muscle weakness   Tendon contractures   Pulmonary fibrosis Hurler's syndrome Hypotrichosis-lymphedema-telangiectasia The Dermatologist pp.47–49 May 2013 Idiopathic retroperitoneal fibrosis Am J Surg 103:514–517, 1962 Kawasaki's disease Lymphedema-distichiasis syndrome The Dermatologist pp.47–49 May 2013 May-Thurner syndrome – iliac vein compression syndrome; congenital anomaly due to compression of left iliac vein right common iliac artery; new vein compression entities Ann Vasc Surg 45:173–178, 2017; Cardiovasc Intervent Radiol 10:89–91, 1987 Meige’s disease The Dermatologist pp.47–49 May 2013 Microcephaly-lymphedema syndrome – with short stature Am J Med Genet 280:506–509, 1998 Microcephaly-lymphedema-chorioretinal dysplasia syndrome – edema of upper and lower extremities; autosomal dominant or recessive Ped Derm 22:373–374, 2005 Neu-Laxova syndrome – widespread ichthyosiform scaling and generalized edema Neurofibromatosis – hemihypertrophy Noonan’s syndrome – lymphedema Int J Dermatol 23:656–657, 1984 Olmsted syndrome Proteus syndrome – hemihypertrophy POEMS syndrome (Takatsuki syndrome, Crowe-Fukase syndrome) (osteosclerotic myeloma) – peripheral edema, osteosclerotic bone lesions, peripheral polyneuropathy, hypothyroidism, and hypogonadism, hyperpigmented sclerodermoid plaque of thighs, scrotal edema, testicular hypertrophy, gynecomastia Blood Reviews 21:285–299, 2007; JAAD 55:149–152, 2006; JAAD 21:1061–1068,

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1989; Cutis 61:329–334, 1998; Nippon Shinson 26:2444–2456, 1968; edema of the lower legs NEJM 372:67–73, 2015 Reflex sympathetic dystrophy (complex regional pain syndrome) – erythema and edema; muscle wasting JAMA Derm 150:640–642, 2014; JAAD 35:843–845, 1996; Arch Neurol 44:555–561, 1987

Angiokeratoma corporis diffusum (Fabry’s disease (alpha galactosidase A) – X-linked recessive; stasis edema of legs JAAD 17:883– 887, 1987; NEJM 276:1163–1167, 1967 Ankle edema of the elderly – dependent lymphedema Aortic aneurysm Clin Exp Rheumatol 9:309–310, 1991

Sly syndrome – mucopolysaccharidosis type VII

Aortitis, infectious Nippon Naika Gakkai Zasshi 88:895–896, 1999

Turner’s syndrome – congenital lymphedema of upper and lower extremities and neck JAAD 50:767–776, 2004

Aortocaval fistula Ann Thoracic Cardiovasc Surg 13:135–138, 2007

Whipple’s disease (Tropheryma whipplei) – non-palpable purpura, chronic leg edema, arthralgias; large dilated abdominal lymphatics; diarrhea, weight loss, abdominal pain, generalized hyperpigmentation, pulmonary hypertension, eye, cardiovascular, and neurologic disease Clin Infect Dis 41:519–520,557–559, 2005 Yellow nail syndrome BJD 156:1230–1234, 2007; BJD 134:307– 312, 1996

TOXINS Arsenic – non-pitting edema Dermatol Clinics 29:45–51, 2011

TRAUMA Total arthroplasty J Arthroplasty 14:333–338, 1999 Bladder distention – bladder compression of the iliac veins Conn Med 62:313, 1998

Arteriosclerosis with limb ischemia Eur J Vasc Surg 17:419–423, 1999 Arteriovenous fistula (between iliac artery and vein) - right heart failure; edema of lower extremities with erythema (venous congestion) NEJM 367:2241–2247, 2012 Arteriovenous malformation Capillary leak syndrome BJD 150:150–152, 2004 Eosinophilic granulomatosis with polyangiitis – bilateral pitting edema with necrotic vasculitis and palpable purpura AD 139:715– 718, 2003 Compartment syndrome Am J Med 113:580–586, 2002 Congenital abnormalities of the abdominal or thoracic lymphatics The Dermatologist pp.47–49 May 2013 Congenital aplasia of the thoracic duct The Dermatologist pp.47–49 May 2013 Congestive heart failure (right sided) Am J Med 113:580–586, 2002 Constrictive pericarditis Am J Med 113:580–586, 2002

Burns Am J Med 113:580–586, 2002

Erythrocyanosis – may have ulceration, erythema, keratosis pilaris, desquamation, nodular lesions, edema, and fibrosis

Femoropopliteal artery by-pass J Cardiovasc Surg 34:389–393, 1993

Erythromelalgia – edema and bullae of legs BJD 151:708–710, 2004; BJD 143:868–872, 2000

High altitude edema JAMA 239:2239, 1978

Giant cell arteritis – unilateral pitting edema Clin Rheumatol 18:82–84, 1999

Immersion foot (trench foot) due to ice, cold water, and fans – acral cyanosis, mottled coloration, marked edema of feet, maceration, bullae, erosions, painful ulcers, pain JAAD 69:169–171, 2013 Lymph node excision Neonatal cold injury – facial erythema or cyanosis; firm pitting edema of extremities spreads centrally resulting in total body edema; skin is cold; mortality of 25% Rook p.482, 1998, Sixth Edition; Br Med J 1:303–309, 1960 Plantaris muscle tear – swelling and pain of calf Medicine 56:151– 164, 1977 Post-physical trauma (degloving injury) Post-surgical Am J Med 113:580–586, 2002 Radiotherapy – lymphedema Br J Surg 73:580–584, 1986 Ruptured medial head of gastrocnemius muscle Saphenectomy Jpn J Thorac Cardiovasc Surg 47:559–562, 1999

Hypoplasia of the peripheral lymphatics The Dermatologist pp.47–49 May 2013 Immobility – dependency – jet flight leg Lancet 347:832–833, 1996; travel, tight clothing, arthritis, polio, wheelchair-bound Inferior vena cava obstruction or stenosis Am J Med 113:580–586, 2002; Eur J Med Research 1:334–338, 1996 Intestinal lymphangiectasis Am J Case Rep 17:512–522, 2016 Klippel-Trenaunay syndrome – port wine stain with lymphatic malformation and lymphedema JAAD 65:893–906, 2011 Lipodermatosclerosis JAAD 28:585–590, 1993 Lymphangioma, diffuse BJD 134:1135–1137, 1996; AD 129:194– 197, 1993 Lymphangioma circumscriptum with underlying lymphatic malformation – lymphedema of limb BJD 83:519–527, 1970

Trench foot (immersion foot) – edematous legs

Lymphangiomyomatosis – lymphedema of one or both legs Cancer 31:455–461, 1973

X-ray overexposure

Lymphatic malformation

Surgical scars

Aagenaes syndrome (hereditary cholestasis with lymphedema) – autosomal recessive; lymphedema of legs due to congenital lymphatic hypoplasia; pruritus, growth retardation Textbook of Neonatal Dermatology, p. 334, 2001

Lymphedema – familial and congenital (Milroy’s disease (mutation in VEGFR-3)), Meige’s syndrome (familial with onset in late childhood or puberty), (lymphedema praecox), lymphedema tarda JAAD 56:353–370, 2007; Cutis 38:105, 1986; primary lymphedema with distal obliteration – bilateral; proximal obliteration – unilateral; congenital – one or more extremities, face, genitalia, lymphangiomas, protein-losing enteropathy, chylous disease, vascular malformations; acquired lymphedema BJD 163:296–301, 2010

Acute hemorrhagic edema of infancy Clin Inf Dis 61:1553, 1624– 1625, 2015; JAAD 59:684–695, 2008

Lymphedema hypotrichosis telangiectasis with mutation in SRY-related HMG-box18 (SOXS18)

VASCULAR DISEASES

Agenesis of venous valve – ankle edema

Erosions (Superficial Ulcers)

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Lymphocoele secondary to renal transplant – edema of leg, scrotum, and suprapubic region Ann Int Med 100:254, 1984

Synovial sarcoma Clin Orthop 364:220–226, 1999

Elephantiasis verrucosa nostra (nostras verrucosa) – lymphostasis verrucosa cutis; chronic lymphedema – congenital, inherited, acquired; associated with obesity, infection, chronic venous insufficiency; cobblestoning, edema, hyperkeratotic plaques of lower legs and feet NEJM 370:2520, 2014; JAAD 64:1104–1110, 2011; Cutis 62:77–80, 1998; elephantiasis nostras of penis AD 137:1095– 1100, 2001; lymphedema of vulva Arch Pathol Lab Med 124:1697– 1699, 2000

Venous thrombosis – swelling and pain of calf; edema of ankle BMJ 320:1453–1456, 2000

Tenosynovitis

EROSIONS (SUPERFICIAL ULCERS)

Megalymphatics – lymphedema of legs

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Parkes-Weber syndrome – arteriovenous malformation with multiple arteriovenous fistulae along extremity with limb (usually leg) overgrowth; arteriovenous shunting; cutaneous red stain; lymphedema; high output congestive heart failure, hypertrophied digits with severe deformity; red foot JAAD 56:541–564, 2007;

Bullous pemphigoid – early signs of bullous pemphigoid – urticarial lesions, dermatitis, excoriations BJD 167:1111–1117, 2012; p200 pemphigoid JAAD 71:185–191, 2014; anti-laminin-gamma 1 pemphigoid BJD 168:1367–1369, 2013

Curr Prob in Dermatol 13:249–300, 2002; BJD 19:231–235, 1907 Phlegmasia cerulea dolens – massive proximal venous thrombosis resulting in arterial insufficiency; triad of asymmetric leg edema, hemorrhagic bullae, cyanosis, acral necrosis, pain NEJM 370:1742– 1748, 2014; Cardiovasc Surg 1:518–523, 1993 Post-phlebitic syndrome – pain, edema, night cramps, hemosiderin deposition, dermatitis Phlebology 11:2–5, 1996 Post-reperfusion syndrome – massive edema of muscles; may lead to amputation; peripheral cyanosis, livedo reticularis, edema of foot; myocardial injury, renal failure Int Wound J March 3, 2014; Semin Vasc Surg 22:52–57, 2009; Plast Reconstr Surg 117:1024–1033, 2006 Primary intestinal lymphangiectasia – autosomal dominant, lower limb edema, loss of immunoglobulin and lymphocytes into gastrointestinal tract Am J Med Genet 66:378–398, 1996

Dermatitis herpetiformis – elbows, knees, buttocks, face JAAD 64:1017–1024, 2011 Epidermolysis bullosa acquisita BJD 171:1022–1030, 2014; Ped Derm 31:241–244, 2014 Fogo selvagem AD 143:895–899, 2007 Graft vs. host reaction, acute, of the newborn JAAD 38:712–715, 1998; plantar erythema, TEN-like erosions, flat-topped papules Ped Derm 30:335–341, 2013 Hyper IgE syndrome – retroauricular fissures AD 140:1119–1125, 2004 IgA pemphigus – submammary intertrigo resembling subcorneal pustular dermatosis AD 138:744–746, 2002; erosions of face and scalp JAAD 43:546–549, 2000 Lichen planus pemphigoides JAAD 36:638–640, 1997

Restrictive cardiomyopathy Am J Med 113:580–586, 2002

Linear IgA disease – personal observation

Stewart-Bluefarb syndrome – arteriovenous malformation of leg with multiple fistulae and port wine stain-like purplish lesions (Mali’s acroangiodermatitis/pseudo-Kaposi’s sarcoma) – brown macules, purple nodules and plaques, edema, varicose veins, hypertrichosis, cutaneous ulcers, enlarged limb JAAD 65:893–906, 2011; Hautarzt 51:336–339, 2000

Linear IgA/IgG bullous dermatosis – dyshidrosiform bullae of palms, herpetiform bullae, cutaneous erosions, tongue erosions JAMA Derm 149:1308–1313, 2013

Deep vein thrombosis – personal observation Thrombophlebitis migrans (Trousseau’s sign) – strong association with internal malignancy Circulation 22:780, 1960 Tricuspid valvular disease Am J Med 113:580–586, 2002 Vasculitis – chronic unilateral painful leg swelling J Rheumatol 15:1022–1025, 1988 Venous gangrene – personal observation Venous obstruction Venous stasis – acute or chronic Phlebology 5:181–187, 1990; with or without stasis dermatitis Venous congestion, acute Venous thrombosis (deep vein thrombophlebitis) (DVT) – swelling and pain of calf; edema of ankle Am J Med 113:580–586, 2002; BMJ 320:1453–1456, 2000

UNILATERAL FOOT EDEMA Freiberg's infarction – avascular necrosis of metatarsal head Lymphedema tarda Plantar fasciitis Am J Roentgenol 173:699–701, 1999 Plantar neuroma

Lupus erythematosus – neonatal lupus erythematosus Ped Derm 15:38–42, 1998; congenital lupus erythematosus – erosions with atrophy and scarring Ped Derm 27:109–111, 2010; neonatal lupus erythematosus with RNP antibodies – varicelliform erosions and facial scars; no cardiac symptoms Ped Derm 30:416–423, 2013; facial edema and crusts as presenting sign of systemic lupus erythematosus JAAD 56:S126–127, 2007 Pemphigus erythematosus NEJM 369:2438–2449, 2013 Pemphigus foliaceus AD 148:1173–1178, 2012; Cutis 78:105–110, 2006; JAAD:S187–189, 2003 Pemphigus herpetiformis – annular arcuate red plaques with edematous borders with erosions and vesicles; red plaque with vesicles, circinate desquamation, erosions, urticarial lesions Ped Derm 34:342–346, 2017; AD 148:531–536, 2012 Pemphigus vegetans – erosions of hands; giant vegetative plaque of vulva; IgG anti-desmocollin-3 antibodies JAMA Derm 149:1209– 1213, 2013 Pemphigus vulgaris – JAAD 71:669–675, 2014; Clin Dermatol 31:374–381, 2013; JID 132:776–784, 2012; BJD 161:313–319, 2009; facial erosions BJD 166:154–160, 2012; BJD 158:382–388, 2008; JAAD 47:875–880, 2002; neonatal JAMA Derm 150:1223– 1224, 2014; JAAD 60:1057–1062, 2009; JAAD 55:S113–114, 2006; JAAD 48:623–625, 2003; Ped Derm 3:468–472, 1986; scalp erosions JAAD 55:S98–99, 2006; abdominal erosions BJD 156:352–356, 2007

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Pemphigus- and pemphigoid-like lesions with acquired palmoplantar keratoderma with tripe pattern – antibodies to desmocollin 3 BJD 157:168–173, 2007

DRUGS

Rheumatoid arthritis – erosive pustular dermatitis of the scalp Int J Dermatol 34:148, 1995

Benznidazole – toxic epidermal necrolysis BJD 175:604–607, 2016

X-linked hypogammaglobulinemia - pyoderma Medicine (Baltimore) 85:193–202, 2006

CONGENITAL DISEASES Aplasia cutis congenita AD 134:1121–1124, 1998; unilateral aplasia cutis congenital Ped Derm 21:454–457, 2004; aplasia cutis congenita and epidermolysis bullosa BJD 170:866–873, 2014; J Med Chir Pharm 26:556–557, 1967; aplasia cutis congenital type V – with associated fetus papyraceus or placental infarcts; symmetric linear erosions of extremities Ped Derm 28:467–469, 2011 Congenital erosive and vesicular dermatosis with reticulated scarring – preterm infant with vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis, hyperthermia, ocular abnormalities, neurodevelopmental abnormalities Ped Derm 36:939–941, 2019; JAAD 69:909–915, 2013; Ped Derm 29:756– 758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985; most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails Ped Derm 30:387–388, 2013; Ped Derm 26:735–738, 2009; JAAD 58:S104–106, 2008; Ped Derm 24:384–386, 2007; Ped Derm 22:55–59, 2005; Clin Exp Derm 30:146–148, 2004; Dermatol 194:278–280, 1997; JAAD 32:873–877, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987   Differential diagnosis:    Aplasia cutis congenita   Amniotic adhesions   Cutaneous trauma   Epidermolysis bullosa    Focal dermal hypoplasia   Intrauterine infection    Intrauterine or perinatal trauma Congenital ichthyosiform erythroderma Congenital localized absence of skin, epidermolysis bullosa simplex, and pyloric atresia Ped Derm 14:359–362, 1997 Erosions in neonates Ped Derm 33:543–548, 2016   Intravenous fluid extravasation   Tape stripping   Scalp pressure ulcers; scalp electrode   Pulse oximeter burn Heterotopic brain or glial tissue – scalp erosion Intrauterine epidermal necrosis JAAD 38:712–715, 1998 Linear porokeratosis – presenting as erosions Ped Derm 12:318– 322, 1995 Lumpy scalp syndrome Meningocele – scalp erosion Sucking blisters – linear erosions of radial forearm, wrist, or hand Cutis 62:16–17, 1998;

DEGENERATIVE DISORDERS Age-related thinning of skin – skin fragility Reflex sympathetic dystrophy JAAD 35:843–845, 1996

Acral erosions – docetaxel Capecitabine – red scrotum; crusts and erosions AD 147:1123– 1124, 2011 Checkpoint inhibitors – Stevens-Johnson syndrome JAAD 80:990– 997, 2019 Doxycycline JAAD 66:862–863, 2012 Fixed drug eruption – oxcarbazepine (Trileptal) – erosion of penis AD 147:362–364, 2011 Gefitinib – streaky hyperpigmented eroded plaques; necrolytic migratory erythema-like JAMA Derm 152:947–948, 2016 Granulocyte colony stimulating factor – exudative and erosive facial plaques; neutrophilic dermatosis associated with myelodysplastic syndrome AD 144:643–648, 2008 Ibuprofen-induced vasculitis IL-2 reactions JAMA 258:1624–1629, 1987 Imatinib mesylate – pseudo-PCT; hemorrhagic bullae of side of hand; crusts and erythema of dorsal hands Ped Derm 31:603–607, 2014 Immune checkpoint inhibitors – CTLA-4, PD-1/PD-L1 inhibitors – bullous pemphigoid Clin in Dermatol 38:94–104, 2020 Irritant dermatitis from topical medicaments Drug-induced linear IgA disease – TEN-like large erosions BJD 169:1041–1048, 2013 Methotrexate necrosis Nivolumab – lichen planus pemphigoides; bullae, erosions, red plaques Cutis 103:224–226, 2019 Pemphigus, drug-induced – captopril, sulfasalazine, d-penicillamine, bucillamine, cetapril, thioprinine BJD 171:544–553, 2014 Penicillamine-induced pemphigus foliaceus AD 133:499–504, 1997 Pseudo-porphyria cutanea tarda JAAD 33:551–573, 1995  Amiodarone Photodermatology 5:146–147, 1988  Benoxaprofen  Bumetanide  Chlorthalidone   Chronic renal failure with or without hemodialysis  Ciprofloxacin  Cyclosporine  Dapsone  Erythropoietin  Etretinate  Finasteride  5-fluorouracil  Furosemide  Imatinib  Nabumetone BJD 142:1067–1069, 2000; BJD 138:549–5500, 1998   Nalidixic acid  Naproxen  Pyridoxine  Sulfonylureas   Tanning bed  Tetracycline   Tiaprofenic acid  Torsemide  Voriconazole JAMA Derm 153:333–334, 2017 Radiation recall – erythema, vesiculation, erosions, hyperpigmentation; dactinomycin and doxorubicin Mayo Clin Proc 55:711–715, 1980; edatrexate, melphalan, etoposide, vinblastine, bleomycin, fluorouracil, hydroxyurea, methotrexate

Erosions (Superficial Ulcers) Retinoid skin fragility Toxic epidermal necrolysis JAAD 71:278–283, 2014; JAAD 69:173–184, 2013; SKINmed 10:373–383, 2012; AD 147:719–723, 2011 Vasculitis – drug-induced Voriconazole – in immunosuppressed patients; chronic phototoxicity with aggressive squamous cell carcinomas; sunburn-like erythema, multiple lentigines, multiple actinic keratoses, cheilitis, exfoliative dermatitis, telangiectasias JAAD 62:31–37, 2010; Photodermatol Photoimmunol Photomed 23:29–31, 2007; JAAD 53:341–345, 2005; Int J Dermatol 43:768–771, 2004

EXOGENOUS AGENTS Benzocaine – erosive papulonodular diaper dermatitis JAAD 55:S74–80, 2006

Gram negative web space infections JAAD 45:537–541, 2001; AD 141:658, 2005; JAAD 8:225–228, 1983 Granuloma inguinale – early Grocer’s itch JAAD 80:1428–1434, 2019 Hand, foot, and mouth disease – Coxsackie A16, Enterovirus 71, Coxsackie A6 – Kaposi’s varicelliform eruption JAAD 75:1–16, 2016 Herpes simplex, – JAAD 60:484–486, 2009; congenital herpes simplex – shawl-like giant erosion covering upper back; giant polycyclic erosive patches JAAD 60:312–315, 2009; red patch with erosions – Kaposi’s varicelliform eruption in Darier’s disease JAAD 72:481–484, 2015; intrauterine, congenital; herpes simplex folliculitis; eczema herpeticum; linear HSV; geometric glossitis Herpes zoster Histoplasmosis – disseminated histoplasmosis BJD 144:205–207, 2001 Impetigo, bullous

Cement burns – calcium oxide in soccer players; crusts and erosions Cutis 61:182, 1998

Insect bite

Chlorhexidine gluconate-impregnated central access catheter dressings JAMA Derm 149:195–199, 2013

Leishmaniasis – impetigo-like leishmaniasis Clin Dermatol 38:140–151, 2020;

Cocaine abuse – “coke bugs” (excoriations) JAAD 80:1428–1434, 2019; JAAD 69:135–142, 2013; Stevens-Johnson syndrome JAAD 59:483–487, 2008 Diaper dermatitis – erosions Fiberglass dermatitis – linear erosions JAAD 80:1428–1434, 2019 Pseudo-porphyria cutanea tarda from tanning beds – personal observation Senneca laxative – blistering erosive diaper dermatitis; diamondshaped erosion of buttocks with linear borders aligning with diaper edge; spares perianal area and gluteal cleft AD 148:402–404, 2012; Pediatrics 107:178–179, 2001 Sulfur spring dermatitis – painful punched out erosions and pits Cutis 94:223–225, 2014

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Intertrigo

Multiple rat bites – comma-shaped crusting on hands and face Cutis 53:302–304, 1994 Mycobacteria chelonae BJD 171:79–89, 2014 Mycobacterium tuberculosis – military tuberculosis Mycoplasma pneumonia (MIRM) – erosive eyelid dermatitis, hemorrhagic erosive cheilitis, penile erosions, perianal erosions JAMA Derm 156:144–150, 2020 Noma neonatorum Pet-induced dermatitis JAAD 80:1428–1434, 2019 Pitted keratolysis Protothecosis BJD 146:688–693, 2002; Am J Clin Pathol 61:10–19, 1974 Pseudomonas, neonatal

INFECTIONS AND INFESTATIONS

Scabies JAAD 80:1428–1434, 2019

Amebiasis – perianal erosions Ped Derm 23:231–234, 2006; amebic abscesses

Staphylococcal scalded skin syndrome – erythroderma, bullae, erosions BJD 166:213–215, 2012; Zentralseit Kinderheilkd 2:3–23, 1878

Aspergillosis, neonatal

Streptococcal infection, group B

Avian mite dermatitis JAAD 80:1428–1434, 2019

Syphilis – congenital; primary (chancre); secondary syphilis – widespread erosions in HIV+ man J Drugs in Dermatol 10:1335–1336, 2011

Candidiasis, erosive – erosion interdigitalis blastomycetica Caterpillar and moth dermatitis JAAD 80:1428–1434, 2019 Chancroid Chikungunya fever – Stevens-Johnson syndrome and toxic epidermal necrosis Ped Derm 35:392–396, 2018 Cytomegalovirus – widespread erosions; anogenital ulcers JAAD Case Rep 27:57–59, 2019; BJD 171:670–671, 2014; scrotal ulcer J Cut Med Surg 20:567–569, 2016 Dermatophytosis Eczema vaccinatum – progressive vaccinia; benign generalized vaccinia Cutis 101:87–90, 2018 Ehrlichiosis – macular and papular erosions, petechiae, edema, vesicles, purpuric plaques JAAD 75:1–16, 2016 Gonococcal infection – primary cutaneous gonococcal infection

Toxic shock syndrome Trichophyton erinacei – pustules and erosion of dorsal hand; pet hedgehog JAMA Derm 154:967–968, 2018 Trichosporosis, neonatal Vaccinia – local dissemination Varicella, intrauterine Zygomycosis, neonatal

INFILTRATIVE DISORDERS Bullous mastocytosis Ped Derm 19:220–223, 2002 Congenital self-healing Langerhans cell histiocytosis (Hashimoto-­ Pritzker disease) – multiple erosions in neonate JAMA Derm

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150:649–650, 2014; J Dermatol 29:48–49, 2002; AD 107:263–270, 1973 Congenital self-healing reticulohistiocytosis – generalized scaling atrophic and erosive patches BJD 149:191–192, 2003 Langerhans cell histiocytosis

INFLAMMATORY DISEASE Crohn’s disease – metastatic Crohn’s disease – red papules and plaques with overlying scale/crust; red scaly plaque with shallow ulcer; red plaques and nodules; abscess-like lesions JAAD 71:804–813, 2014; J Eur Acad Dermatol Venereol 15:343–345, 2001

hereditary coproporphyria; transient neonatal porphyrinemia; adult onset congenital erythropoietic porphyria with myelodysplasia syndrome AD 145:948–949, 2009; late onset congenital erythropoietic porphyria (uroporphyringen II synthase) – erosions, milia, crusts BJD 175:1346–1350, 2016; hepatoerythropoietic porphyria – extreme photosensitivity, skin fragility in sun-exposed areas, hypertrichosis, erythrodontia, pink urine, sclerodermoid changes AD 146:529–533, 2010; Protein C, S or fibrinogen deficiency Pruritus due to systemic disease JAAD 80:1428–1434, 2019 Tyrosinemia type II (Richner-Hanhart syndrome) – erosions of palms on thenar and hypothenar eminences, soles, tips of fingers JAAD 35:857–859, 1997

Edematous scarring vasculitic panniculitis JAAD 2:37–44, 1995 Erythema multiforme with epidermal necrosis; Stevens-Johnson syndrome JAAD 71:278–283, 2014 Pyoderma gangrenosum – superficial pyoderma gangrenosum BJD 159:1377–1378, 2008 Stevens-Johnson syndrome/toxic epidermal necrolysis BJD 174:1194–1227, 2016 Toxic epidermal necrolysis BJD 174:1194–1227, 2016;

NEOPLASTIC Proliferative actinic keratosis – red patch with erosions Derm Surg 26:65–69, 2000 Basal cell carcinoma – single or multiple Acta Pathol Mibrobiol Scand 88A:5–9, 1980 Dermoid cyst

BJD 68:355–361, 1956

Lymphoma, including cutaneous T-cell lymphoma

METABOLIC DISEASES

Bullous macroglobulinosis – bullae, scars, erosions, papules of dorsal hands JAAD 77:1145–1158, 2017

Lymphomatoid papulosis

Acrodermatitis enteropathica – perioral erosions; mutation in SLC39A4 encodes ZIP4 zinc transporter BJD 161:184–186, 2009; acquired zinc deficiency from parenteral nutrition – acral erosions and bullae, cheilitis Ped Derm 36:520–523, 2019

Melanocytic nevi – erosions overlying giant congenital melanocytic nevi;

Biotin-responsive multiple carboxylase deficiency

Porokeratosis – congenital linear porokeratosis Ped Derm 12:318– 322, 1995

Calcinosis cutis, metastatic – multiple erosions with yellow crusts SKINmed 11:314–315, 2013 Carcinoid syndrome – pellagrous dermatitis (erosions from skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea BJD 152:71–75, 2005; AD 77:86–90, 1958 Crohn’s disease – personal observation

Merkel cell carcinoma – erosion of nose JAAD 42:366–370, 2000 Paget’s disease – erosion of nipple BJD 165:440–441, 2011

Porokeratotic adnexal ostial nevus (conifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic lesions with comedones; presents as red patch with red and atrophic linear and curvilinear erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAAD 61:1060–1069, 2009; BJD 103:435–441, 1980; BJD 101:717–722, 1979

Essential fatty acid deficiency Kwashiorkor – crusting and superficial erosions in the diaper area AD 137:630–636, 2001; perinasal erosions Cutis 67:321–327, 2001 Liver disease, chronic (cirrhosis) – zinc deficiency; generalized dermatitis of erythema craquele (crackled and reticulated dermatitis) with perianal and perigenital erosions and crusts; cheilitis, hair loss Ann DV 114:39–53, 1987 Methylmalonic acidemia, cobalamin C type; erosive erythema; newborn and early infancy AD 133:1563–1566, 1997 Multiple nutritional deficiencies – personal observation Porphyria – hepatoerythropoietic porphyria AD 138:957–960, 2002; variegate porphyria – protoporphyrin oxidase deficiency BJD 159:503–505, 2008; porphyria cutanea tarda Clin Inf Dis 56:851– 852, 898–899, 2013; NEJM 369:1356, 2013; variegate; homozygous variegate porphyria – erosions, photosensitivity, short stature Cutis 88:73–76, 2011; BJD 144:866–869, 2001; congenital erythropoietic porphyria BJD 148:160–164, 2003; erythropoietic porphyria, erythropoietic protoporphyria – crusted erosions in photodistribution with weathered appearance BJD 171:412–414, 2014; BJD 155:574–581, 2006; erythropoietic protoporphyria – erosions of fingertips from pulse oximeter NEJM 369:659, 2014;

PARANEOPLASTIC DISEASES Glucagonoma syndrome – erosive intertrigo AD 144:795–800, 2008 IgA subcorneal pustular dermatosis-like pemphigus with myeloma – superficial blisters and erosions BJD 172:296–298, 2015 Paraneoplastic pemphigus – multiple erosions JAAD 80:1544–1549, 2019; BJD 174:930–932, 2016; BJD 172:831–834, 2015; BJD 160:468–470, 2009; AD 141:1285–1293, 2005; erosions and necrotic crusts of face BJD 145:127–131, 2001; erosive paronychia BJD 147:725–732, 2002

PHOTODERMATOSES Actinic cheilitis – hyperkeratotic, scaling, erosive cheilitis JAAD 66:173–184, 2012 Actinic prurigo Stat Pearls Oct 8, 2019 Dermatoheliosis with minor trauma Hydroa vacciniforme – crusts of helices Cutis 88:245–253, 2011

Erosions (Superficial Ulcers)

PRIMARY CUTANEOUS DISEASES Acne excoriee des jeunes fille (skin picking disorder) J Dermatol Treat 29:277–280, 2018 Atopic dermatitis – infra-auricular fissure JAAD 66:1009–1010, 2012 Autosomal recessive exfoliative ichthyosis – congenital erythroderma, diffuse hyperkeratosis, palmoplantar keratoderma, palmoplantar peeling, hyperhidrosis, erosions; mutation in cysteine protease inhibitor A (cystatin A) BJD 172:1628–1632, 2015 Autosomal recessive inherited skin fragility – mutations in EXPH5 BJD 170:196–199, 2014 Brachioradial pruritus Cutis 102:185–186,189–190, 2018 Bullous dermolysis of the newborn (form of autosomal dominant epidermolysis bullosa or recessive dystrophic epidermolysis bullosa) – hypopigmented patches; giant bullae of hand and foot; erosions, tongue erosions, milia Ped Derm 30:736–740, 2013 Congenital bullous ichthyosiform erythroderma Darier’s disease Hum Mutat 38:343–356, 2017 Dyshidrotic dermatitis Epidermolytic hyperkeratosis Epidermolysis bullosa – all forms JAAD 70:1103–1126, 2014; junctional epidermolysis bullosa letalis (laminin 5 defect) – scalp, perioral and periorbital erosions; junctional epidermolysis bullosa mitis – scalp erosions; ulcers, crusts, and atrophy; anonychia; pitted enamel of teeth; hyperkeratotic lesions of legs; epidermolysis bullosa, generalized junctional (Herlitz type) The Dermatologist, October 2016,pp17–18; BJD 170:1056–1064, 2014; acantholytic epidermolysis bullosa AD 131:590–595, 1995; junctional, non-Herlitz type; COL17A1 mutations (GABEB) – erosions and dental enamel hypoplasia BJD 160:1094–1097, 2009; BJD 156:861–870, 2007; BJD 157:596–598, 2007; epidermolysis bullosa, progressive junctional type – palmoplantar hyperkeratosis (non-lethal localized junctional EB) – legs and feet only; hyperkeratosis with erosions of soles J R Soc Med 78 (Suppl 11); 32–33, 1985; epidermolysis bullosa pruriginosa (DDEB) – vesicles, atrophic skin with erosions and crusting, hypertrophic scarring, hypopigmentation, and linear scars, milia AD 147:956–960, 2011; JAAD 56:S77–81, 2007; recessive dystrophic epidermolysis bullosa JAAD 73:56–61, 2015; BJD 161:1089–1097, 2009; epidermolysis bullosa simplex, generalized severe – hoarse cry in newborn, erosions Ped Derm 37:393–395, 2020 Epidermolysis bullosa – alpha6-beta4 epidermolysis bullosa – mild blistering and crusting, severe skin fragility, patchy hyperpigmentation of elbows; onychogryphosis; yellow-brown discoloration of teeth with enamel defects BJD 169:115–124, 2013

integrin alpha-B mutation; other mutations in KRT14, Plec, DST-e, DSP, JUP, Tgm-5, EXPH5 (exophilin 5) Ped Derm 34:166–171, 2017; BJD 174:452–453, 2016; NEJM 366:1508–1514, 2012 Epidermolysis bullosa pruriginosa (dystrophic epidermolysis bullosa) – hyperkeratosis of the nails, excoriations, lichenification of shins, white papules JAMA Derm 149:727–731, 2013 Epidermolysis bullosa, severe – mutation in keratin 5p.E477K Ped Derm 36:1007–1009, 2019 Epidermolytic ichthyosis – personal observation Erosive adenomatosis (papillary adenomatosis) of the nipple – blood-­stained or serous discharge; enlarged nipple; eroded nipple; erythema, ulcer, crusted dermatitis, granular appearance, papule on nipple JAAD 47:578–580, 2002; JAAD 43:733–751, 2000; superficial papillary adenomatosis of the nipple JAAD 33:871–875, 1995; JAAD 12:707–715, 1985 Erosive pustular dermatosis of the scalp (chronic atrophic erosive dermatosis of the scalp and extremities) – in elderly; hyperkeratotic crusting, pustules, erosions, atrophy, scarring alopecia JAMA Derm 155:734, 2019; JAMA Derm 152:694–697, 2016; JAAD 66:680–686, 2012; AD 145:1340–1341, 2009; JAAD 60:521–522, 2009; AD 144:795–800, 2008; JAAD 57:421–427, 2007; JAAD 57:S11–14, 2007; Ped Derm 23:533–536, 2006; AD 139:712–714, 2003; BJD 148:593–595, 2003; Dermatol Surg 27:766–767, 2001; JAAD 28:96–98, 1993; Hautarzt 43:576–579, 1992; Ann DV 118:899–901, 1991; BJD 118:441–444, 1988(S); BJD 100:559–566, 1979; BJD 97(Suppl):67–69, 1977; after perinatal scalp injury Ped Derm 23:533–36, 2006; chronic atrophic erosive dermatosis of the scalp and extremities JAAD 57:421–427, 2007 Erythema of Jacquet – erosive diaper dermatitis with umbilicated papules Ped Derm 15:46–47, 1998 Fissured hand dermatitis – loss of function mutation in filaggrin BJD 166:46–53, 2012 Hailey-Hailey disease Hum Mutat 38:3343–356, 2017; JID 126:2370–2376, 2006; Nat Genet 24:61–65, 2000 Ichthyosis bullosa of Siemens Intertrigo, erosive – personal observation Lethal acantholytic epidermolysis bullosa – universal alopecia, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010 Lichen planus – bullous; erosive lichen planus of the flexures Clin Exp Dermatol 18:169–170, 1993; ulcerative lichen planus of the soles BJD 165:441–443, 2011; AD 127:405–410, 1991; of feet Lichen planus pemphigoides – papules and erosions Ped Derm 31:751–753, 2014

Epidermolysis bullosa, generalized dystrophic BJD 168:904–906, 2013

Lichen sclerosus – personal observation

Epidermolysis bullosa – ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013

Pustular psoriasis

Epidermolysis bullosa with pyloric atresia (plectin mutation) – extensive area of erosion lower back (aplasia cutis congenita) BJD 168:808–814, 2013; mutation of integrin beta4 gene J Dermatol Sci 78:61–66, 2015 Junctional epidermolysis bullosa, generalized intermediate BJD 179:973–975, 2018 Epidermolysis bullosa, autosomal recessive – blisters and erosions, mild skin fragility, fatal interstitial lung disease, nephrotic syndrome, sparse fine hair, large dystrophic toenails with distal onycholysis;

321

Nummular dermatitis Vorner's palmoplantar keratoderma – newborn infant with erosive erythematous dermatitis

PSYCHOCUTANEOUS DISEASE Delusions of parasitosis – crusted erosions JAAD 80:1428–1434, 2019; JAAD 76:779–791, 2017; white atrophic scars with erosions and ulcers NEJM 371:2115–2123, 2014; Semin Dermatol 2:189 –195, 1983; Arch Derm Syphilol 54:39–56, 1946 Dementia JAAD 80:1428–1434, 2019

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Factitial dermatitis (dermatitis artefacta) JAAD 76:779–791, 2017; Ped Derm 32:604–608, 2015; Ped Derm 21:205–211, 2004; JAAD 1:391–407, 1979 Neurotic and psychogenic excoriations Compr Psychiatry 27:381– 386, 1986 Schizophrenia JAAD 80:1428–1434, 2019

SYNDROMES Acantholytic ectodermal dysplasia (similar to McGrath syndrome) – curly hair, palmoplantar keratoderma, skin fragility, hyperkeratotic fissured plaques with perioral involvement, red fissured lips, nail dystrophy BJD 160:868–874, 2009 Amniotic band syndrome (disorders of amniotic band sequence) – congenital erosions AD 134:1121–1124, 1998 Ankyloblepharon-ectrodactyly-cleft (AEC) lip/palate syndrome – widespread congenital erosions of scalp and extremities; congenital erythroderma; widely spaced nipples, alopecia of scalp and eyebrows Ped Derm 28:15–19, 2011; AD 141:1567–1573, 2005; AD 134:1121–1124, 1998; generalized fissured erosions of trunk BJD 149:395–399, 2003; erosive diaper dermatitis Ped Derm 28:313– 317, 2011 Congenital insensitivity to pain – bruises, burns, lacerations, and fractures mimicking child abuse Pediatr Emerg Care 12:116–121, 1996 Conradi-Hunermann syndrome (chondrodysplasia punctata) – scalp erosions Bart's syndrome Ectodermal dysplasia with clefting Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral papules with hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; loss of function of PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin Ped Derm 36:255–257, 2019; BJD 166:36–45, 2012; Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Ehlers-Danlos syndrome – increased skin fragility; type VIII – autosomal dominant; skin fragility, abnormal scarring, severe early periodontitis with loss of adult dentition by end of third decade; cigarette paper scars of shin; marfanoid habitus (tall, long limbs, arachnodactyly); triangular face, prominent eyes, thin nose, prematurely aged appearance, thin skin with prominent veins, no joint hypermobility, easy bruising, blue sclerae JAAD 55:S41–45, 2006 Goltz's syndrome AD 134:1121–1124, 1998 Histiophagocytic syndrome – parvovirus B19-induced histiophagocytic syndrome in systemic lupus erythematosus; violaceous plaques and erythema of scalp, face, and back with erosions and erosive cheilitis JAAD 57:S111–114, 2007 Incontinentia pigmenti – scalp erosions JAAD 47:169–187, 2002 IRAK-4 deficiency (homozygous mutations of IL-receptorassociated kinase 4 gene) – cutaneous infections with

Staphylococcus aureus; abscesses, cellulitis, impetigo JAAD 54:951–983, 2006 Kindler’s syndrome – bullae, crusts, erosions; cigarette paper atrophy over dorsal hands and feet; hyper- and hypopigmentation; poikiloderma; nail dystrophy, keratoderma of palms and soles, esophageal, anal, vaginal, and urethral stenosis, ectropion, severe periodontal disease JAMA 306:767–768, 2011; Actas Dermosifiliogr 96:677–680, 2005 Laryngo-onycho-cutaneous syndrome (Shabbir syndrome) – autosomal recessive; symblepharon, crusted erosions of elbows, anonychia with granulation tissue of nail bed, mucosal nodule of hard palate; hoarse cry and laryngeal stenosis, chronic granulation tissue, conjunctival inflammation with polypoid granulation tissue, tooth enamel hypoplasia; laminin alpha 3A isoform mutation (LAMA 3A) with N-terminal deletion of LAMA 3A Derm Clinics 28:211–222, 2010; Ped Derm 24:306–308, 2007; Ped Derm 23:75–77, 2006; Cornea 20:753–756, 2001; Arch Dis Child 70:319–326, 1994; JAAD 29:906–909, 1993; Clin Dysmorphol 1:3–14, 1992; Eye 5:717–722, 1991; Biomedica 2:15–25, 1986 Lesch-Nyhan syndrome – X-linked recessive; hypoxanthineguanine phosphoribosyltransferase deficiency; self-mutilation; biting of lower lip Ped Derm 13:169–170, 1996; AD 94:194–195, 1966 Lipoid proteinosis – autosomal recessive; early lesions with crusted erosions, small vesicles, linear cribriform scars; over time diffuse thickening and yellowing of skin; loss of function mutation in extracellular matrix protein 1 (ECM1) gene Ped Derm 26:91–92, 2009; Ped Derm 23:1–6, 2006; BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002; Virchows Arch Pathol Anat 273:286–319, 1929 Mid-face toddler excoriation syndrome (MITES) – erosions of face Ped Derm 37:345–346, 2020 Mucoepithelial dysplasia - perioral erosions Necrolytic migratory erythema (glucagonoma syndrome) Neu-Laxova syndrome – harlequin fetus-like changes; resembles restrictive dermopathy Patau’s syndrome (trisomy 13) – parieto-occipital scalp defects, abnormal helices, low set ears, loose skin of posterior neck, simian crease of hand, hyperconvex narrow nails, polydactyly Ped Derm 22:270–275, 2005 Peeling skin syndrome – red macules, erosions, desquamation, xerosis; mutation in corneodesmosin Ped Derm 37:371–380, 2020: JAMA Derm 151:225–226, 2015 Reactive arthritis Restrictive dermopathy – autosomal recessive; erythroderma at birth, with extensive erosions and contractures; taut shiny skin, uniformly fatal Ped Derm 16:151–153, 1999; AD 134:577–579, 1998; AD 134:1121–1124, 1998 Riley-Day syndrome (familial dysautonomia) – mottling with excoriations Skin fragility-ectodermal dysplasia syndrome – autosomal recessive; mutation in plakophilin 1 (PKP1); widespread superficial scale crust, erosions, painful thickening and fissuring of palms and soles, anomalies of hair and nails BJD 154:546–550, 2006 Skin fragility-woolly hair syndrome – autosomal recessive; woolly hair, palmoplantar keratoderma, skin fragility; desmoplakin abnormality BJD 166:894–896, 2012; JID 118:232–238, 2002 Trigeminal trophic syndrome – Wallenberg's syndrome JAAD 61:160–161, 2009 Trisomy 13- congenital erosions AD 134:1121–1124, 1998

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TOXINS Caustic substances NEJM 382:1739–1748, 2020  Alkalis   Ammonium hydroxide    Sodium hydroxide or potassium hydroxide   Sodium hypochlorite  Acids   Acetic acid   Hydrochloric acid   Oxalic acid   Phosphoric acid   Selenous acid   Sulfuric acid   Miscellaneous caustics    Cationic detergents – benzalkonium chloride   Hydrofluoric acid   Hydrogen peroxide   Phenol   Zinc chloride

antibiotics after topical sensitization (systemic eczematous contact dermatitis) AD 115:360–361, 1979; AD 111:266, 1975; systemic allergic contact dermatitis to nickel from ingestion of metal coins Ped erm 28:53–54, 2011; J Ped Gastroenterol Nutr 23:74–76, 1996; JAAD 25:855–856, 1991; J Pediatr 95:428–429, 1979 Bullous pemphigoid J Dermatol Sci 78:21–25, 2015; JAAD 41:658–659, 1999; JAAD 39:827–830, 1998; JAAD 29:293–299, 1993; JAAD 21:1099–1104, 1989; lichenoid bullous pemphigoid JAAD 39:691–697, 1998 CD4+ lymphocytopenia – photoaccentuated erythroderma with CD 4+ T lymphocytopenia JAAD 35:291–294, 1996 Cellular immunodeficiency with immunoglobulins – diffuse erythema Common variable hypogammaglobulinemia Am J Med 78:523–528, 1985 Dermatomyositis JAAD 26:489–490, 1992; including paraneoplastic dermatomyositis JAAD 39:653–654, 1998; juvenile dermatomyositis Ped Derm 27:418–420, 2010; Ped Derm 26:234–235, 2009; pityriasis rubra-like presentation Ped Derm 24:151–154, 2007 Deficiency of IL-36 receptor antagonist (DITRA) – erythrodermic pustular psoriasis BJD 174:417–420, 2016

TRAUMA Air bag chemical injury JAAD 46:S25–26, 2002 Burns, third degree – radiation, thermal, ultraviolet, chemical Cutis 86:249–257, 2010 Cardioversion (defibrillation) – hypopigmented, atrophic, telangiectatic, crusted erythematous plaque of back with rim of hyperpigmentation; delayed onset of years AD 145:1411–1414, 2009 Child abuse – stocking or glove distribution; perineal burns – annular with central sparing (doughnut lesions) around buttocks JAAD 57:371–392, 2007 Erosive pustular dermatosis of face – following cosmetic resurfacing JAMA Derm 153:1021–1025, 2017 Explosion injuries from E-cigarettes NEJM 375:1400–1402, 2016 Fire-related inhalational injury NEJM 375:464–469, 2016 Immersion foot due to ice, cold water, and fans – acral cyanosis, mottled coloration, marked edema of feet, maceration, bullae, erosions, painful ulcers, pain JAAD 69:169–171, 2013 Perinatal trauma, iatrogenic injury; forceps delivery Salt-ice challenge – burns

VASCULAR DISORDERS Granulomatosis with polyangiitis – crusting and erosions of nostrils, nasal septum, pharynx, larynx, trachea AD 130:861–867, 1993 Hemangiomas of infancy – perineal and lip ulceration as presenting manifestations Pediatrics 99:256, 1997 Perinatal gangrene of the buttock in the neonate Vascular malformations

ERYTHRODERMAS (EXFOLIATIVE ERYTHRODERMA)  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Epidermolysis bullosa acquisita – erythroderma with islands of sparing JAMA Derm 151:678–680, 2015 Fogo selvagem (endemic pemphigus) Ped Derm 23:132–135, 2006; JID 107:68–75, 1996; JAAD 32:949–956, 1995 Graft vs. host reaction, acute – toxic epidermal necrolysis or exfoliative erythroderma BJD 144:901–902, 2001; JAAD 38:369– 392, 1998; Ped Derm 12:311–313, 1995; exfoliative erythroderma with palmoplantar keratoderma AD 143:1157–1162, 2007; chronic Immunodeficiency syndrome with erythroderma, diarrhea of infancy Pediatr 81:66–72, 1988 Linear IgA/IgG bullous dermatitis Eur J Dermatol 29:220–221, 2019 Lupus erythematosus – subacute cutaneous LE JAAD 19:388–392, 1988; erythroderma and bullae JAAD 48:947–949, 2003 Pemphigus erythematosus NEJM 369:2438–2449, 2013 Pemphigus foliaceus Ped Derm 24:172–176, 2007; AD 83:52–70, 1961 Pemphigus vulgaris J Drugs Dermatol 12:210–216, 2013 Severe combined immunodeficiency syndrome – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks); erythroderma, seborrheic dermatitis-like eruption; mutations in cytokine common gamma chain, JAK3, RAG1 or RAG2, IL-7Rgamma, adenosine deaminase BJD 178:335–349, 2018; Ped Derm 26:213–214, 2009; AD 144:342–346, 2008; AD 136:875–880, 2000; J Pediatr 123:564–572, 1993; Ped Derm 8:314–321, 1991 Still’s disease BJD 145:187–188, 2001; adult onset Still’s disease – generalized erythema J Eur Acad Dermatol Venereol 19:360–363, 2005 Subacute combined immunodeficiency (SCID) – erythroderma with alopecia Ped Derm 28:494–501, 2011   Omenn syndrome   Major histocompatibility complex class II deficiency   Adenosine deaminase deficiency Systemic contact dermatitis – neomycin, parabens Transfusion reaction

CONGENITAL DISORDERS

Airborne contact dermatitis

Autosomal recessive epidermolytic hyperkeratosis – congenital erythroderma BJD 162:1384–1387, 2010

Allergic contact dermatitis – rhus BJD 142:937–942, 2000; cyanamide Contact Dermatitis 40:160–161, 1999; ingested

Collodion baby (lamellar desquamation of the newborn) – bright erythema with glisteny, translucent membrane; ectropion, everted

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lips, fish-like mouth, bleeding within dried fissured membrane; peels in 1–2 days in large sheets; seen in lamellar ichthyosis, non-bullous ichthyosiform erythroderma Ann DV 113:773–785, 1986; trichothiodystrophy BJD 106:705–710, 1982; ichthyosis vulgaris Ann DV 113:773–785, 1986; X-linked ichthyosis JAMA 202:485–488, 1967; Netherton’s syndrome Mod Probl Paediatr 20:40–49, 1978; neutral lipid storage disease Dermatologica 177:237–240, 1988; SjogrenLarsson syndrome Ann DV 113:773–785, 1986; mild lamellar ichthyosis Ped Derm 9:95–97, 1992; Gaucher’s disease Arch Dis Child 63:854–856, 1988; loricrin keratoderma – congenital ichthyosiform erythroderma and collodion baby BJD 145:657–660, 2001 Congenital bullous ichthyosiform erythroderma Epidermolytic ichthyosis (bullous ichthyosiform erythroderma) – autosomal dominant, erythroderma at birth, mutations in keratin 10 Exp Dermatol 8:120–123, 1999 Non-bullous congenital ichthyosiform erythroderma Ped Derm 19:285–292, 2002; Ped Derm 16:497–508, 1998 Congenital psoriasis BJD 140:538–539, 1999 Harlequin fetus Ped Derm 20:421–426, 2003 Mastocytosis – congenital diffuse cutaneous mastocytosis – neonatal bullous erythroderma Ped Derm 28:542–546, 2011 Sclerema neonatorum

DEGENERATIVE Involutional erythroderma (idiopathic erythroderma) – elderly men

Codeine Contact Derm 32:120, 1995 Crizotinib Toxicol Letter 319:102–110, 2020 Dapsone Lepr Rev 57:179–180, 1986 Dideoxyinosine-associated papuloerythroderma of Ofuji in HIV disease Dermatology 195:410–411, 1997 Diflunisal Dilantin and radiation – erythema multiforme; personal observation Diltiazem J Toxicol Clin Toxicol 35:101–104, 1997 Drug reaction with eosinophilia and systemic symptoms (DRESS) – morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, urticarial papular-confluent; facial edema, lymphadenopathy BJD 170:866–873, 2014; BJD 169:1071–1080, 2013; BJD 168:391– 401, 2013; Ped Derm 28:741–743, 2011; JAAD 68:693–705, 2013; AD 146:1373–1379, 2010; association with HHV-6; lymphadenopathy, circulating atypical lymphocytes, abnormal liver function tests AD 137:301–304, 2001; due to anticonvulsants Cutis 86:305–308, 2010; Ped Derm 26:536–546, 2009 Enalapril – interstitial granulomatous drug reaction BJD 158:1143– 1144, 2008 Erythropoietin Medicina Clinica 115:158, 2000 Ethylenediamine AD 115:360, 1979 Eretinate BJD 112:373, 1985 Fluorouracil GM-CSF AD 128:1055–1059, 1992 Gold – pityriasis rubra pilaris-like eruption; personal observation

DRUG-INDUCED Acute generalized exanthematous pustulosis (pustular drug eruption) BJD 169:1223–1232, 2013; Cutis 83:291–298, 2009 Allopurinol Amiodarone BMJ 296:1332–1333, 1988 Ampicillin Ann Acad Med Singapore 14:693–695, 1985 Organic arsenic Aztreonam Barbiturates Bevacizumab – recombinant humanized antibody against endothelial growth factor; exfoliative dermatitis J Drugs Dermatol 1:1052– 1055, 2013

Griseofulvin Hydantoin Hydroxychloroquin Chin Med J (Eng) 131:1887–1888, 2018 Icodextrin – palmoplantar pustulosis, erythroderma, generalized exanthematous pustulosis AD 137:309–310, 2001 Imatinib/dasatinib/nilotinib (tyrosine kinase inhibitors) – morbilliform eruption JAAD 71:217–227, 2014 Immune checkpoint inhibitors – CTLA4, PD-1/PD-L1 inhibitors – erythrodermic psoriasis; pityriasis rubra-like erythroderma Clin in Dermatol 38:94–104, 2020 Indinivir Clin Inf Dis 25:1268–1269, 1997 Interleukin 1 alpha followed by ifosfamide, carboplatin, and etoposide – sunburn-like erythroderma JAAD 35:705–709, 1996

Bismuth ingestion JAAD 37:489–490, 1997

Isoniazid

Boric acid poisoning JAAD 7:667–73, 1982

IVIG BJD 151:721, 2004

Budesonide (corticosteroid) Contact Dermatitis 27:121–122, 1992

Kit and BCR-ABL inhibitors – imatinib, nilotinib, dasatinib – facial edema morbilliform eruptions, pigmentary changes, lichenoid reactions, psoriasis, pityriasis rosea, pustular eruptions, DRESS, Stevens-Johnson syndrome, urticarial, neutrophilic dermatoses, photosensitivity, pseudolymphoma, porphyria cutanea tarda, small vessel vasculitis, panniculitis, perforating folliculitis, erythroderma JAAD 72:203–218, 2015

Captopril Carbamazepine Ped Derm 13:316–320, 1996 Carboplatin J Clin Oncol 17:1141, 1999 Cefoxitin Checkpoint inhibitors – pityriasis rubra pilaris-like eruptions JAAD 80:990–997, 2019

Lithium

Chloroquine

M-CSF Am J Hematol 47:147–148, 1994

Chlorpromazine

Mefloquine Clin Inf Dis 16:341–342, 1993

Cimetidine

MEK inhibitors (selumetinib, cobimetinib, trametinib) – hypersensitivity reactions; erythroderma with islands of sparing JAMA Derm 151:78–81, 2015

Ciprofloxacin-induced pityriasis rubra pilaris-like reaction Clodronate BMJ 307:484, 1993 Clofazimine

Mercury Metformin Eur J Case Rep Int Med 6:001119

Erythrodermas (Exfoliative Erythroderma) 325 Methylprednisolone (IV) Contact Dermatitis 25:68–70, 1991

Nevirapine Pak J Pharm Sci 32:221–222, 2019

Voriconazole – in immunosuppressed patients; chronic phototoxicity with aggressive squamous cell carcinomas; sunburn-like erythema, multiple lentigines, multiple actinic keratoses, cheilitis, exfoliative dermatitis, pseudo-porphyria cutanea tarda, telangiectasias JAAD 62:31–37, 2010

Nifedipine Ann Pharmacother 28:967, 1994

Vinca alkaloids

Nitrofurantoin

Zidovudine J Allergy Clin Immunol 98:234–235, 1996

Minocycline Mitomycin Int J Derm 24:472, 1985

p-aminosalicylic acid Penicillin d-penicillamine Pentostatin BMJ 319:549, 1999 Phenobarbital Intern Med 32:182–184, 1993 Phenylbutazone Phenytoin BJD 134:1109–1112, 1996; phenytoin-induced pseudo CTCL AD 133:499–504, 1997 Plaquenil JAAD 12:857–862, 1985 Practolol Prostaglandin – acute flush Proton pump inhibitors (omeprazole, lansoprazole) BJD 141:173– 175, 1999 Pseudolymphoma, drug-induced AD 132:1315–1321, 1996; JAAD 38:877–905, 1998 Quinidine Ranitidine Rifampin – red man syndrome Streptomycin Sulfasalazine AD 134:1113–1117, 1998 Sulfonamides Sulfonylureas Teicoplanin

EXOGENOUS AGENTS Boric acid ingestion – “boiled lobster” erythema with subsequent desquamation; cardiogenic shock, seizures, renal failure Clinical Toxicology 47:432, 2009; Inf Dis in Ob Gyn 6:191–194, 1998 Cyanamide Contact Derm 40:160–161, 1999 Rhus – ingestion of Rhus as folk medicine remedy BJD 142:937– 942, 2000 Selenium excess – exfoliative dermatitis St. John’s wort BJD 143:1127–1128, 2000 Tear gas

INFECTIONS AND INFESTATIONS AIDS – recalcitrant erythematous desquamating disorder JAAD 17:507–508, 1987; Clin Inf Dis 18:942, 1999; initial presentation of seroconversion JAAD 28:167–173, 1993; Dermatologica 183:143– 145, 1991; CD 8+ erythroderma of HIV infection JAAD 41:722–727, 1999 Bee sting AD 120:1595, 1984 Candidiasis, congenital AD 129:897–902, 1993; invasive systemic candidiasis in premature neonate (C. albicans) Ped Derm 21:260– 261, 2004; candidiasis in bedridden patient – personal observation

Telaprevir – exfoliative erythroderma AD 148:1215–1217, 2012

Coccidioidomycosis – toxic erythema Dermatol Clin 7:227–239, 1989

Terbinafine

Dengue hemorrhagic fever JAAD 46:430–433, 2002

Thalidomide Dermatology 189:179–181, 1994; toxic pustuloderma Clin Exp Dermatol 22:297–299, 1997

Dermatophytosis – generalized Trichophyton rubrum dermatophytosis in congenital ichthyosiform erythroderma JAAD 20:1133–1134, 1989

Thiacetazone Thiotepa – diffuse erythema, desquamation, and hyperpigmentation JAAD 58:575–578, 2008 Ticopidine NEJM 340:1212, 1999 Timolol maleate eyedrops (beta blocker) JAAD 37:799–800, 1997 Tobramycin Tocainide Ann Int Med 107:693–696, 1987 Toxic epidermal necrolysis JAAD 69:173–184, 2013; SKINmed 10:373–383, 2012; BJD 68:355–361, 2005; AD 111:1433–1437, 1975

Ebola virus hemorrhagic fever JAAD 75:1–16, 2016 Ehrlichiosis – human monocytic ehrlichiosis (E. chaffeensis) – resembles toxic shock syndrome MMWR 65:1–44, May 23, 2016; Am J Med 95:351–357, 1993 Hepatitis – fulminant Cutis 37:56, 1986 Herpes simplex – eczema herpeticum – personal observation HHV 6 J Clin Pathol 47:762–763, 1994 Histoplasmosis J Cutan Pathol 29:215–225, 2002; AD 101:216–219, 1970

Tramadol

Leishmaniasis Revista Clinica Espanola 191:454, 1992

Trazodone – erythema multiforme minor; personal observation

Leprosy – erythroderma An Bras Dermatol 94:86–92, 2019

Trovofloxacin Ann Pharmacother 33:1122, 1999

Mycobacterium tuberculosis – exfoliative erythroderma as a manifestation of pulmonary tuberculosis BJD 148:346–348, 2003

Vancomycin – red man syndrome, acute erythroderma, angioedema, hypotension, dyspnea, chest pain – due to histamine release from basophils and mast cells; may be caused by ciprofloxacin, amphotericin B, rifampicin, and teicoplanin JAAD 60:890– 891, 2009; Postgrad Med 75:41–43, 1999; vancomycin-induced linear IgA disease mimicking toxic epidermal necrolysis AD 146:1419–1424, 2010 Vemurafenib – toxic epidermal necrolysis BJD 172:1454–1455, 2015

Pediculosis corporis – erythroderma sparing hands and face AD 143:682, 2007 Salmonella toxic shock syndrome – personal observation Scabies – crusted (Norwegian) scabies Ped Derm 17:410–414, 2000; AD 124:123,126, 1988; Norwegian scabies in psoriasis Cutis 94:156–159, 2014; crusted scabies mimicking erythrodermic psoriasis with hyperkeratotic feet Ped Derm 31:753–754, 2014

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Scarlet fever Spider bite (brown recluse spider) – acute generalized exanthematous pustulosis JAAD 55:525–529, 2006 Staphylococcal scalded skin syndrome – erythroderma, bullae, erosions BJD 166:213–215, 2012; Eur J Clin Microbiol Infect Dis 15:499–503, 1996; JAAD 30:319–324, 1994; J Clin Microbiol 26:1283–1286, 1988 Staphylococcal toxic shock syndrome – personal observation Staphylococcal scarlatina Streptococcal sex syndrome – postcoital lower extremity streptococcal erythroderma in women JAMA 257:3260–3262, 1987 Strongyloides stercoralis, disseminated – exfoliative erythroderma BJD 171:911–913, 2014 Syphilis – congenital Toxic epidermal necrolysis – Staphylococcal, Streptococcal, Klebsiella, Escherichia coli Ped Derm 11:331–334, 1994 Toxic shock syndrome Pediatr Rev 17:319, 321–322, 1996; Staphylococcus aureus toxic shock syndrome Curr Prob in Dermatol 14:183–220, 2002; JAAD 39:383–398, 1998; Clin Inf Dis 18:942–945, 1994; J Infect 16:87–103, 1988; NEJM 303:1436– 1442, 1980; associated with Adenovirus Type 3 Clin Inf Dis 33:260–262, 2001; streptococcal toxic shock syndrome Curr Prob in Dermatol 14:183–220, 2002; JAAD 39:383–398, 1998; JAAD 24:786–787, 1991; BMJ 301:1006–1007, 1990; Pseudomonas species Lancet 2(8517):1218–1219, 1986; Group C streptococci Arch Intern Med 152:882, 884, 1992; Group B streptococcal toxic shock syndrome AD 140:163–165, 2004 Toxoplasmosis – exfoliative erythroderma Int J Derm 33:s129–130, 1994

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – psoriasiform exfoliative dermatitis JAAD 50:159–161, 2004; JAAD 41:335–337, 1999; J Dermatol 20:49–55, 1993; AD 114:191–197, 1978 Sarcoid – erythrodermic sarcoid with multiple red papules JAMA Derm 153:335–336, 2017; JAAD 66:699–716, 2012; JAAD 35:826, 1996; Hautarzt 61:675, 1986; BJD 95:93–97, 1976; may mimic pityriasis rubra pilaris BJD 95:93–97, 1976 Whipple's disease – erythroderma; macular and reticulated erythema; Addisonian hyperpigmentation; Tropheryma whipplei JAAD 60:277–288, 2009

METABOLIC Biotinidase deficiency (biotin-responsive multiple carboxylase deficiency) – neonatal and infantile; autosomal recessive; neonatal – holocarboxylase synthetase deficient; first 6 weeks of life; erythrodermic with fiery red intertriginous dermatitis AD 123:1696–1698, 1987; Pediatrics 68:113–118, 1981; infantile – biotinidase deficient; after 3 months of life, intertriginous rash with keratoconjunctivitis, xerosis, generalized pallor, periorificial dermatitis, alopecia, branny desquamation, and atrophic glossitis Semin Dermatol 10:296–302, 1991; JAAD 9:97–103, 1983; Citrullinemia Essential fatty acid deficiency Gaucher’s disease – collodion babies Arch Dis Child 66:667, 1991 Hyper IgE syndrome JAAD 36:106–107, 1997 Idiopathic hypoparathyroidism AD 109:242–244, 1974 Kwashiorkor Ped Derm 16:95–102, 1999 Maple syrup urine disease AD 129:384–385, 1993

INFILTRATIVE Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100 JAAD 74:513–520, 2016 Langerhans cell histiocytosis Acta DV 99:99–100, 2019 Mastocytosis – diffuse cutaneous mastocytosis Ped Derm 19:375– 381, 2002; Dermatology 187:127–129, 1993; Cutis 49:189–192, 1992 telangiectasia macularis eruptiva perstans Cutis 71:357–359, 2003 Reticulohistiocytosis, diffuse cutaneous – personal observation

INFLAMMATORY DISEASES Erythema multiforme, Stevens-Johnson syndrome – acute erythroderma BJD 174:1194–1227, 2016 Kikuchi’s disease (histiocytic necrotizing lymphadenitis) – generalized erythema, multiple red to red-brown papules of face, scalp, chest, back, arms; red plaques; erythema and acneiform lesions of face; morbilliform, urticarial, and rubella-like exanthems; red or ulcerated pharynx; cervical adenopathy; associations with SLE, lymphoma, tuberculous adenitis, viral lymphadenitis, infectious mononucleosis, and drug eruptions AD 142:641–646, 2006; BJD 144:885–889, 2001; JAAD 36:342–346, 1997; Am J Surg Pathol 14:872–876, 1990 Pseudolymphoma – CD 8+ pseudolymphoma in HIV disease JAAD 49:139–141, 2003

Serotonin syndrome – use of proserotonergic agents (monoamine oxidase inhibitors, tricyclic antidepressants, SSRIs, opiate analgesics, over-the-counter cough medicines, antibiotics, weight-reduction agents, anti-emetics, antimigraine agents, drugs of abuse, herbal supplements; tachycardia, hypertension, hyperthermia, mydriasis, hyperactive bowel sounds, diaphoresis; severe manifestations include shock, agitated delirium, muscular rigidity, hypertonicity NEJM 352:1112–1120, 2005 Thyrotoxicosis – pruritic exfoliative dermatitis Dermatology 184:157, 1992

NEOPLASTIC Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) – erythroderma and edema J Dermatol 33:628–631, 2006; AD 138:1208–1212, 2002; J Pediatr 130:352–357, 1997; AD 128:193– 200, 1992 Leukemia – HTLV-1 (acute T-cell leukemia) JAAD 49:979–1000, 2003; T-cell prolymphocytic leukemia – facial purpuric plaques; petechial periorbital eruption JAAD 55:467–477, 2006; Cancer 52:2049–2054, 1983; T-cell prolymphocytic leukemia AD 148:1199– 1204, 2012 Lymphoma/leukemia – acute myelogenous leukemia JAAD Cas Rep 5:121–123, 2019; cutaneous T-cell lymphoma (Sezary syndrome) JAAD 70:205–220, 2014; NEJM 369:559–569, 2013; Cutis 89:229–232,236, 2012; JAAD 27:427–433, 1992; JAAD 41:254–259, 1999; Semin Oncol 26:276–289, 1999; exfoliative CTCL mimicking chronic actinic dermatitis BJD 160:698–703, 2009; CTCL of T-/null cells – erythroderma and ulcerated nodules BJD

Erythrodermas (Exfoliative Erythroderma) 327 172:1637–1641, 2015; adult T-cell leukemia/lymphoma BJD 155:617–620, 2006; presenting as papuloerythroderma Clin Exp Dermatol 20:161–163, 1995; BJD 130:773–736, 1994; syringotropic CTCL BJD 148:349–352, 2003; angioimmunoblastic T-cell lymphoma JAAD 38:992–994, 1998; JAAD 36:290–295, 1997; BJD 104:131–139, 1981; HTLV-1 (adult T-cell leukemia) Blood 117:3961–3967, 2011; JAAD 46:S137–141, 2002; JAAD 36:869– 871, 1997; JAAD 27:846–849, 1992; Hodgkin’s disease, non-Hodgkin’s lymphoma, leukemia, myelodysplasia; chronic T-cell lymphocytic leukemia JAAD 8:874–878, 1983; Ki-1 (CD30) positive anaplastic large cell lymphoma JAAD 47:S201–204, 2002; HTLV-1 leukemia/lymphoma – nodulotumoral lesions, nodules, ulcerated nodules, multipapular lesions, red plaques, red patches, erythroderma JAAD 72:293–301, 2015; large cell B-cell lymphoma CMJ Care Rep May 20, 2019 Lymphoproliferative disease of granular lymphocytes JAAD 32:829–33, 1995 Malignant histiocytosis Int J Derm 29:214–216, 1990; malignant histiocytosis mimicking kwashiorkor Ped Derm 19:5–11, 2002 Monoclonal T-cell dyscrasia of undetermined significance AD 141:361–367, 2005 Myelodysplasia Postgrad Med J 63:481–482, 1987 Plasmacytic pseudolymphoma Int J Dermatol 37:778–780, 1998 Waldenstrom’s macroglobulinemia with neoplastic cellular infiltrate – deck chair sign JAAD 52:S45–47, 2005

PARANEOPLASTIC Small cell bronchogenic carcinoma Curr Probl Cancer Aug 30, 2019; 100499 Esophageal carcinoma JAAD 13:311, 1985 Fallopian tube carcinoma Obstet Gynecol 71:1045–1047, 1988 Gastric carcinoma Am J Gastroenterol 79:921–923, 1984

Alopecia mucinosa (follicular mucinosis) Clin Exp Dermatol 12:50–52, 1987 Atopic dermatitis Clin Exp Derm 25:535–543, 2000 Darier's disease JAAD 23:926–928, 1990 Dyshidrotic dermatitis Cureus 10:e3005, 2018 Episodic nontoxic erythema – recurrent swelling of the extremities followed by generalized tender sunburn-like erythema, followed by exfoliation AD 132:1387–1388, 1996 Erythrokeratodermas  Annular migrating erythrokeratoderma – slowly migrating orange-­ brown plaques of buttocks and legs Hautarzt 42:634–637, 1991   Erythrokeratoderma with ataxia   Erythrokeratoderma with physical retardation and deafness  Erythrokeratoderma with periorificial lesions – around mouth, genital, and perianal regions; acral involvement and pachyonychia Hautarzt 34:465–467, 1983   Erythrokeratoderma hiemalis Hautarzt 45:776–779, 1994  Erythrokeratoderma variabilis (Mendes da Costa syndrome) – autosomal dominant; dark red fixed plaques with transient polycyclic red macules with fine scale JID 113:1119–1122, 1999; Ped Derm 12:351–354, 1995  Genodermatose en cocardes (Degos’ syndrome) – fixed plaques; large round transient plaques Clin Exp Dermatol 24:173–174, 1999   Keratosis-ichthyosis-deafness (KID) syndrome   Localized erythrokeratoderma Hautarzt 7:231, 1956  Progressive partially symmetrical erythrokeratoderma with deafness (Schnyder’s syndrome) – inner ear deafness, myopathy, mental retardation, keratitis; resemble KID syndrome but lesions are localized Int J Pediatr Otorhinolaryngol 15:279–289, 1988; Hautarzt 33:416–419, 1982  Symmetric progressive erythrokeratoderma (Gottron’s syndrome) – autosomal dominant; large fixed geographic symmetric scaly red-­orange plaques; shoulders, cheeks, buttocks, ankles, wrists AD 122:434–440, 1986; Dermatologica 164:133–141, 1982

Leukemia – chronic lymphocytic leukemia

Erythema neonatorum – generalized hyperemia of newborn, fades in 1–2 days

Lymphoma – Hodgkin's disease JAAD 49:772–773, 2003

Hailey-Hailey disease BJD 99:553–560, 1978

Myelodysplastic syndrome – generalized granulomatous dermatitis presenting as erythroderma with diffuse red patches with papules AD 147:331–335, 2011

Ichthyosiform erythroderma with generalized pustulosis BJD 138:502–505, 1998

Other occult malignancies Paraneoplastic pemphigus JAMA Derm 149:111–113, 2013

PHOTOSENSITIVITY DISEASES Chronic actinic dermatitis, including actinic reticuloid JAAD 38:877–905, 1998; J Clin Pathol 51:154–158, 1998; AD 131:1298– 1303, 1995; Semin Derm 9:47–54, 1990 Persistent light reaction to musk ambrette Cutis 54:167, 1994 Photoaccentuated erythroderma associated with CD4+ lymphopenia JAAD 35:291–294, 1996 PUVA burn from tanning salon – personal observation Solar urticaria JAAD 65:336–340, 2011

PRIMARY CUTANEOUS DISEASE Adolescent–onset ichthyosiform–like erythroderma with lichenoid tissue reaction BJD 144:1063–1066, 2001

Keratosis lichenoides chronica Australas J Dermatol 41:247–249, 2000 Lamellar ichthyosis – transglutaminase 1 mutation Eur J Human Genet 6:589–596, 1998 Lethal acantholytic epidermolysis bullosa – universal alopecia, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010 Lichen myxedematosus – personal observation Lichen planus; Am J Dermatopathol 13:358–364, 1991 Necrolytic acral erythema – acral velvety hyperpigmented and hyperkeratotic plaques of distal dorsal feet; red palms with desquamation, erythroderma with flaccid bullae, edema and desquamation of face, onychodystrophy and onychomadesis; hepatitis C Cutis 84:301–304, 2009 Non-bullous congenital ichthyosiform erythroderma – congenital erythroderma with subsequent generalized scaling BJD 158:1125– 1128, 2008 Papuloerythroderma of Ofuji Clin Exp Dermatol 25:293–295, 2000; Clin Exp Dermatol 23:79–83, 1998; JAAD 26:499–501, 1992; in CTCL JAAD 20:927–931, 1989; J Dermatol 25:185–189, 1998

328 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Pityriasis rosea JAAD 15:159–167, 1986 Pityriasis rubra pilaris Clin in Dermatol 37:657–662, 2019 J Eur Acad Dermatol Venereol 24:881–884, 2010; JAAD 59:S65– 70, 2008; J Dermatol 27:174–177, 2000; JAAD 31:997–999, 1994; familial pityriasis rubra pilaris-erythroderma with islands of sparing; CARD14 gain of function mutation BJD 171:420–422, 2014; Am J Hum Genet 91:163–170, 2012 Poikiloderma vasculare atrophicans Psoriasis BJD 155:156–159, 2006; Eur J Dermatol 9:537–539, 1999; Dermatology 194:102–106, 1997; Dermatol Clin 13:757–770, 1995; congenital erythrodermic psoriasis BJD 140:538–539, 1999; in HIV disease NEJM 380:80, 2019; pustular psoriasis – personal observation Recalcitrant erythematous desquamating disorder (RED) J Clin Inf Dis 24:1274–1275, 1997 Recurrent non-toxic erythema Seborrheic dermatitis – of infancy Textbook of Neonatal Dermatology, p.248, 2001 Senile erythroderma with serum hyper-IgE Dermatologica 183:72– 73, 1991

Dermatitis-eosinophilia syndrome following wasp sting AD 120:1595–1597, 1984 Happle's syndrome – X-linked dominant chondrodysplasia punctata Ped Derm 13:1–4, 1996 Hemophagocytic syndrome (hemophagocytic lymphohistiocytosis), reactive – reacts to B- or T-cell lymphoma or herpes simplex infection; transient generalized morbilliform exanthem; erythroderma, purpuric macules, lymphadenopathy, pancytopenias, increased ferritin, high triglycerides Blood Rev 28:135–142, 2014; Best Pract Res Clin Rheumatol 28:277–292, 2014; Eur Rev Med Pharmacol Sci 16:1414–1424, 2012; BJD 162:547–553, 2010; Crit Rev Oncol Hematol 50:157–174, 2004; familial hemophagocytic syndrome – morbilliform eruptions, purpuric macules, acral blanching red macules, erythroderma and edema JAAD 56:302– 316, 2007; JAAD 56:302–316, 2007; AD 138:1208–1212, 2002;AD 128:193–200, 1992 Hypereosinophilic syndrome – palmoplantar keratoderma with exfoliative erythroderma Allergy 59:673–689, 2004; Ped Derm 15:363–371, 1996; Semin Dermatol 14:122–128, 1995; Blood 83:2759–2779, 1994; in AIDS JAAD 23:202–204, 1990

Vorner's palmoplantar keratoderma - exfoliative erythroderma in infant whose mother has Vorner’s PPK

Hystrix-like ichthyosis-deafness syndrome – postnatal erythroderma, generalized spiky and cobblestoned hyperkeratosis, sensorineural deafness, connexin mutation BJD 146:938–942, 2002

SYNDROMES

Ichthyosis bullosa of Siemens Clin Exp Derm 15:53–56, 1990

Ichthyosiform erythroderma and cardiomyopathy BJD 139:1055– 1059, 1998

Annular epidermolytic ichthyosis – variant of bullous congenital ichthyosiform erythroderma – mutation in keratin 10 JID 111:1220– 1223, 1998

Ichthyosis congenita type IV – erythrodermic infant with follicular hyperkeratosis BJD 136:377–379, 1997

CHILD syndrome (hemidysplasia, ichthyosiform erythroderma, unilateral limb defects (hypoplasia)) – X-linked dominant; unilateral inflammatory epidermal nevus or unilateral ichthyosiform erythroderma with skeletal abnormalities AD 123:503–509, 1987

Keratosis linearis with ichthyosis and sclerosing keratoderma (KLICK syndrome) – autosomal recessive; erythroderma, palmoplantar keratoderma, ainhum, red elbows and knees BJD 153:461, 2005; Acta DV 77:225–227, 1997; Am J Hum Genet 61:581–589, 1997

Congenital reticular ichthyosiform erythroderma (ichthyosis variegata, ichthyosis en cocarde) BJD 139:893–896, 1998; Dermatology 188:40–45, 1994 Conradi-Hunermann syndrome – generalized erythema Hum Genet 53:65–73, 1979 CRIE (congenital reticular ichthyosiform erythroderma) syndrome – ichthyosis en confetti – reticulated erythroderma with guttate hypopigmentation, palmoplantar kertoderma; loss of dermatoglyphics; temporary hypertrichosis of normal skin JAMA Derm 151:15– 16,64–69, 2015; BJD 166:434–439, 2012; JAAD 63:607–641, 2010; Acta DV 83:36–39, 2003; BJD 139:843–846, 1998; Dermatology 188:40–45, 1994; Ann Dermatol Venereol 111:675–676, 1984; Hautarzt 35:522–529, 1984 Ichthyosis en confetti (ichthyosis variegata) – reticulated erythroderma with guttate hypopigmentation, palmoplantar kertoderma; loss of dermatoglyphics; temporary hypertrichosis of normal skin JAMA Derm 151:15–16,64–69, 2015; BJD 166:434–439, 2012; JAAD 63:607–641, 2010; Acta DV 83:36–39, 2003; BJD 139:843– 846, 1998; Dermatology 188:40–45, 1994; Ann Dermatol Venereol 111:675–676, 1984; Hautarzt 35:522–529, 1984

Kawasaki's disease JAAD 69:501–510, 2013

KID syndrome – keratosis, ichthyosis, deafness syndrome – erythrokeratoderma-­like in infancy with hyperkeratotic plaques of elbows, knees, scalp, forehead, cheeks, and perioral region; follicular hyperkeratosis of trunk; sparse scalp hair, eyebrows, lashes, thick nails, and dental anomalies; chronic skin infections Ped Derm 27:653, 2010; Ped Derm 17:115–117, 2000; Ped Derm 13:105–113, 1996; Leiner's syndrome NEJM 282:354, 1976; J Ped 80:879, 1972 MAUIE syndrome – erythroderma with skip areas; micropinnae, alopecia, ichthyosis, and ectropion JAAD 37:1000–1002, 1997 Netherton's syndrome BJD 178:335–349, 2018; Ped Derm 31:90–94, 2014; AD 135:823–832, 1999; BJD 141:1097–1100, 1999; Ped Derm 14:473–476, 1997; Ped Derm 13:183–199, 1996

Degos' syndrome – erythrokeratodermia en cocardes

Neutral lipid storage disease (Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma (non-bullous congenital ichthyosiform erythroderma and neutral lipid storage disease) ; thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness AD 141:798–800, 2005; Am J Dermatopathol 20:79–85, 1998; JAAD 17:801–808, 1987; AD 121:1000–1008, 1985

Degos-Touraine syndrome – incontinentia pigmenti with poikiloderma in photodistribution, bullae of face, extremities; chronic erythroderma with subsequent hyperpigmentation Soc Gr Dermatol Syph 68:6–10, 1961

Omenn's syndrome – autosomal recessive; immunodeficiency; erythroderma with occasional alopecia of scalp and eyebrows; generalized adenopathy with hepatosplenomegaly BJD 178:335– 349, 2018; Ped Derm 14:49–52, 1997; JAAD 25:442–446, 1991

MAUIE (micropinnae, alopecia universalis, congenital erythroderma, ectropion) syndrome JAMA Derm 151:15–16,64–69, 2015

Erythrodermic Infant 329 Peeling skin syndrome type B – autosomal recessive; erythroderma with desquamation; palmar erythema; corneodesmosin (CDSN) mutation BJD 169:1322–1325, 2013 Phakomatosis pigmentovascularis Progressive symmetric erythrokeratoderma – autosomal dominant; hyperkeratotic patches Curr Prob Derm 14:71–116, 2002 Red man syndrome (idiopathic) JAAD 18:1307, 1988 Reactive arthritis syndrome; Semin Arthritis Rheum 3:253–286, 1974 Restrictive dermopathy – autosomal recessive Serotonin syndrome – personal observation Trichothiodystrophy syndromes (Tay syndrome) – BIDS, IBIDS, PIBIDS – autosomal recessive; collodion baby, congenital erythroderma, sparse or absent eyelashes and eyebrows, sulfur deficient short brittle hair with tiger tail banding on polarized microscopy, trichomegaly, brittle soft nails with koilonychia, premature aging, very short stature, microcephaly, sexual immaturity, ichthyosis, photosensitivity, hypohidrosis, high arched palate, dysmyelination of white matter, bird-like facies, abnormal teeth with dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; recurrent infections with neutropenia; ocular abnormalities, osteopenia; socially engaging personality; mutation in one of 3 DNA repair genes (XPB, XPA, TTDA, or TTDN1 JAAD 63:323–328, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Pediatrics 87:571–574, 1991; Am J Med Genet 35:566–573, 1990; JAAD 16:940–947, 1987; Eur J Pediatr 141:147–152, 1984 Vogt-Koyanagi-Harada disease – prodrome erythroderma Dermatology 198:65–68, 1999

Atopic dermatitis AD 136:875–880, 2000 Bruton’s hypogammaglobulinemia Combined immunodeficiency – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks) which progresses to erythroderma (with pachydermatous appearance) Common variable hypogammaglobulinemia Deficiency of interleukin-1 receptor antagonist (DIRA) (IL-1 receptor deficiency) – loss of function mutation of IL1RN; neutrophilic pustular dermatosis with confluent pustules and lakes of pus; infantile pustulosis and exfoliative erythroderma; oral ulcers, joint swelling; periostitis, aseptic multifocal osteomyelitis; increased acute phase reactants Ped Derm 30:758–760, 2013; AD 148:747–752, 2012 Graft vs host disease in severe combined immunodeficiency JAAD 29:863–865, 1993; maternal-­fetal GVHD AD 136:875–880, 2000 Harlequin color change – blanchable erythema on dependent side; aberrant dilatation of peripheral vasculature due to incomplete development of hypothalamus NEJM 369:373, 2013 Hyper IgE syndrome Secretory IgA deficiency AD 136:875–880, 2000 Pemphigus foliaceus Ped Derm 24:172–176, 2007 Severe combined immunodeficiency syndrome – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks); erythroderma, seborrheic dermatitis-like eruption; recurrent otitis media; mutations in cytokine common gamma chain (X-linked recessive), JAK3, RAG1 or RAG2, IL-7Rgamma, adenosine deaminase (autosomal recessive) AD 146:191–196, 2010; Ped Derm 26:213–214, 2009; AD 144:342–346, 2008; AD 136:875–880, 2000; J Pediatr 123:564–572, 1993 ZAP-70 deficiency – primary immune deficiency syndrome Ped Derm 37:561–562, 2020

TOXINS Acute arsenic ingestion BJD 141:1106–1109, 1999

CONGENITAL LESIONS

Scombroid fish poisoning

Autosomal recessive congenital exfoliative ichthyosis – congenital erythroderma, diffuse hyperkeratosis, palmoplantar keratoderma, palmoplantar peeling, hyperhidrosis, erosions; mutation in cysteine protease inhibitor A (cystatin A) BJD 172:1628–1632, 2015; mutation in NIPAL4 (ichthyin) Ped Derm 36:1002–1003, 2019

TRAUMA Burns – acute erythroderma Immersion burn Post-cardiac surgery

VASCULAR DISEASES Generalized port wine stain Stasis dermatitis with autosensitization

ERYTHRODERMIC INFANT AD 136:875–880, 2000

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Alopecia and infantile erythroderma – highly suggestive of an immunodeficiency syndrome including Omenn syndrome AD 136:875–880, 2000

Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis Ped Derm 29:756–758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985; most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails Ped Derm 30:387–388, 2013; Ped Derm 26:735–738, 2009; JAAD 58:S104–106, 2008; Ped Derm 24:384– 386, 2007; Ped Derm 22:55–59, 2005; Clin Exp Derm 30:146–148, 2004; Dermatol 194:278–280, 1997; JAAD 32:873–877, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987   Differential diagnosis:    Aplasia cutis congenita   Amniotic adhesions   Cutaneous trauma   Epidermolysis bullosa    Focal dermal hypoplasia   Intrauterine infection    Intrauterine or perinatal trauma Ichthyosis prematurity syndrome JAAD 66:606–616, 2012

330 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

DRUG-INDUCED

Argininosuccinicaciduria

Ceftriaxone

Biotinidase deficiency AD 136:875–880, 2000

Phenobarbital drug eruption in DiGeorge’s syndrome – personal observation

Carbamoyl phosphate synthetase deficiency Carbohydrate deficient glycoprotein syndromes

Toxic epidermal necrolysis, neonatal BJD 152:150–151, 2005; JAAD 27:340–344, 1992; Ped Derm 2:197–2000, 1985; Dermatologica 169:88–90, 1984

Citrullinemia AD 136:875–880, 2000

Vancomycin

Cobalamin deficiency Cystic fibrosis Essential fatty acid deficiency Gaucher’s disease – collodion babies Arch Dis Child 66:667, 1991

EXOGENOUS AGENTS Chlorhexidine gluconate antibacterial cleanser

INFECTIONS AND INFESTATIONS Aspergillus Bullous impetigo Congenital cutaneous candidiasis AJDC 135:273–275, 1981

Holocarboxylase deficiency Ichthyosiform erythroderma (lamellar ichthyosis or non-bullous congenital ichthyosiform erythroderma) –development of rickets BJD 158:603–606, 2008 Maple syrup urine disease AD 129:384–385, 1993 Methylmalonicacidemia – perioral erosions Porphyria – transient erythropoietic protoporphyria JAAD 35:833– 834, 1996

Dermatophytosis

Propionic acidemia – propionyl-CoA carboxylase deficiency; low isoleucine; generalized exfoliative dermatitis Ped Derm 24:508–510, 2007

Eczema herpeticum

Protein malnutrition

HHV-6

Secretory IgA deficiency AD 136:875–880, 2000

Curvularia

HIV Int J Dermatol 38:896–900, 1999 Parechovirus type 3 – young infants; high fever, poor perfusion, irritability; sepsis-like presentation; erythrodermic rash, abdominal distension, edema, hepatitis; recovery common Clin Inf Dis 60:228–236, 2015 Scabies Staphylococcal scalded skin syndrome Syphilis, congenital J Fam Pract 35:327–329, 1992

NEOPLASTIC DISEASES Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) – erythroderma and edema J Dermatol 33:628–631, 2006; AD 138:1208–1212, 2002; J Pediatr 130:352–357, 1997; AD 128:193– 200, 1992 Leukemia – acute lymphocytic leukemia

Toxic shock syndrome Toxoplasmosis, congenital JAAD 60:897–925, 2009; Int J Dermatol 33:129–130, 1994 Trichophyton rubrum in congenital ichthyosiform erythroderma

PHOTOSENSITIVITY DISORDERS Chronic actinic dermatitis

Trichosporon

PRIMARY CUTANEOUS DISEASES INFILTRATIVE DISORDERS Langerhans cell histiocytosis Derm Ther 26:176–179, 2013; Ped Derm 28:542–546, 2011

Autosomal recessive congenital ichthyosis with ichythyin mutation Exp Dermatol 17:373–382, 2008; J Med Genet 44:615–620, 2007; Hum Mol Genet 13:2473–2482, 2004

Mastocytosis – diffuse cutaneous mastocytosis Ped Derm 36:486– 489, 2019

Autosomal recessive congenital ichthyosis – ichthyosis, erythroderma, collodion baby, contractures of large joints, palmoplantar hyperlinearity, edema of fingers; CYP4F22 mutation BJD 176:1068– 1073, 2017

INFLAMMATORY DISEASES

Autosomal recessive epidermolytic hyperkeratosis – congenital erythroderma BJD 162:1384–1387, 2010

Eosinophilic gastroenteritis Toxic epidermal necrolysis

METABOLIC DISEASES Acrodermatitis enteropathica Aminoaciduria – methylmalonic, argininosuccinicaciduria, maple syrup urine disease (MSUD), propionic acidemia

Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) JID 91:357–361, 1993 Collodion baby – eclabium; congenital erythroderma, ectropion, deformed ears, alopecia; mutation in ABCA12 BJD 166:218–221, 2012 Congenital ichthyosiform erythroderma (autosomal recessive congenital ichthyosis) – with collodion membrane; autosomal recessive; ALOX12B mutation (lipoxygenase) BJD 163:201–204, 2010

Erythrodermic Infant Erythrokeratoderma variabilis Ped Derm 12:351–354, 1995; Ann DV (Stockh) 6:225–258, 1925 Harlequin infant – presenting as non-bullous congenital ichthyosiform erythroderma BJD 135:448–453, 1996 Ichthyosis en confetti – neonatal ichthyosiform erythroderma, hyperpigmented verrucous and cerebriform plaques of heels and neck BJD 176:249–251, 2017 KID (keratosis-ichthyosis-deafness) syndrome – neonatal generalized erythema with diffuse scaling and leathery skin Ped Derm 27:653, 2010 Lamellar ichthyosis AD 136:875–880, 2000 Lethal acantholytic epidermolysis bullosa – universal alopecia, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388–1394, 2010 Non-bullous congenital ichthyosiform erythroderma BJD 158:864– 867, 2008; AD 136:875–880, 2000 Pityriasis rubra pilaris – familial with CARD 14 BJD 17:420–422, 2014 Psoriasis AD 136:875–880, 2000; Ped Derm 12:231–234, 1995 Seborrheic dermatitis AD 136:875–880, 2000 Self-healing collodion baby (self-improving collodion ichthyosis) – autosomal recessive Ped Derm 9:95–97, 1992; may be a premature infant; associated with hypoplasia of nasal and/or auricular cartilage; associated with Sjogren-Larsson syndrome, Gaucher’s disease, and trichothiodystrophy Soc Ped Derm Annual Meeting, July, 2006; transglutaminase-1 mutation AD 148:1191–1195, 2012; JID 120:224–228, 2003; ALOX12B gene AD 144:351–356, 2008; TGM1 mutations BJD 162:448–451, 2010; ALOXE3 JAAD 63:607–641, 2010

SYNDROMES Ankyloblepharon-ectrodactyly-cleft (AEC) lip/palate syndrome – widespread congenital scalp erosions; congenital erythroderma with scaling and erosions; widely spaced nipples, alopecia of scalp and eyebrows Ped Derm 28:15–19, 2011; Int J Dermatol 46:1196–1197, 2007; AD 141:1567–1573, 2005; AD 134:1121–1124, 1998; Ped Derm 10:336–370, 1993; generalized fissured erosions of trunk BJD 149:395–399, 2003 Chanarin-Dorfman syndrome – non-bullous congenital ichthyosiform erythroderma, lipid vacuoles within neutrophils, liver, muscle, and CNS involvement Ped Derm 26:40–43, 2009 CHILD syndrome Am J Med Genet 62:192–194, 1996 Congenital erosive and vesicular dermatosis with reticulate scarring – erythroderma at birth Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995 Conradi-Hunermann-Happle disease (syndrome) – X-linked dominant; mutation in EBP (emopamil-binding protein); mutation in cholesterol metabolism; collodion baby; congenital ichthyosiform erythroderma, linear and whorled (Blaschko-esque) hyperkeratotic bands with diffuse erythema and scale, follicular atrophoderma, atrophic hypochromic areas, atrophoderma vermuculata; sparse hair with patchy scalp alopecia; cataracts, frontal bossing; low nasal bridge; orbital arch hypoplasia; short stature, asymmetric shortening of arms and legs, chondrodysplasia punctata (stippled epiphyses), vertebral defects with scoliosis, cataracts BJD 166:830–838, 2012; AD 147:1073–1076, 2011; BJD 160:1335–1337, 2009; BJD 157:1225–1229, 2007; Ped Derm 15:299–303, 1998; AD 127:539– 542, 1991; JAAD 21:248–256, 1989; Hum Genet 53:65–73, 1979

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CRIE syndrome – congenital reticulated ichthyosiform erythroderma – formerly ichthyosis en confetti (includes ichthyosis variegate, MAUIE syndrome) JAMA Derm 151:64–69, 2015; JAMA Derm 151:15–16, 2015; Acta DV 94:579–582, 2014; Dermatology 188:40–45, 1994 Dorfman-Chanarin syndrome (neutral lipid storage disease) – autosomal recessive; non-bullous congenital ichthyosiform erythroderma; hyperkeratosis of palms and soles, elbows, knees, ankles; acylglycerol recycling defect; mutation in ABHD5 gene Ped Derm 25:326–331, 2008; BJD 144:430–432, 2001; Am J Dermatopathol 20:79–85, 1998 Dubowitz's syndrome Ectodermal dysplasia-skin fragility syndrome – autosomal recessive; plakophillin gene mutation (PKP1) – generalized erythema and peeling at birth; widespread skin fragility, alopecia of scalp and eyebrows, focal palmoplantar keratoderma with painful fissures, hypohidrosis; skin peeling; perioral fissuring and cheilitis; perianal erythema and erosions, follicular hyperkeratosis JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004 Episodic nontoxic erythema – swelling of the extremities followed by generalized tender sunburn-like erythema, followed by exfoliation AD 132:1387–1388, 1996 Erythrokeratoderma-cardiomyopathy syndrome – recurrent infections, wiry or absent hair, dental enamel defects, nail dystrophy, sudden onset congestive heart failure; early death; dominant mutation in desmoplakin Cases of the Year, Pre-AAD Pediatric Dermatology Meeting HID syndrome (hystrix-like ichthyosis with deafness) – autosomal dominant; neonatal erythroderma, shark-skin appearance, sensorineural deafness, spiky and cobblestoned hyperkeratosis, scarring alopecia, occasional punctate keratitis; probably variant of KID syndrome with mutation of connexin 26 (gap junction protein) BJD 146:938–942, 2002 Ichthyosis prematurity syndrome (“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; erythrodermic infant with caseous vernix-like desquamation; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine scaling of scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin (thick vernix caseosa-like covering) (hyperkeratotic scalp) neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4 (FATP4) JAAD 66:606– 616, 2012; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008 Idiopathic hypereosinophilic syndrome BJD 144:639, 2001; Blood 83:2759–2779, 1994 Keratosis-ichthyosis-deafness syndrome (KID syndrome) – autosomal dominant; congenital generalized erythema; hyperkeratotic papules with follicular spiny projections, verrucous plaques of forehead, cheeks, perioral region, elbows, knees, and scalp; scarring alopecia of scalp and eyebrows; red-orange reticulated plaques, scalp cysts, follicular occlusion triad, paronychia with chronic mucocutaneous candidiasis, nodules (trichilemmal tumors, squamous cell carcinomas), progressive corneal scarring with blindness; bilateral deafness; mutation in GJB2 (connexin 26) JAAD 69:127–134, 2013; Ped Derm 27:651–652, 2010; Ped Derm 26:427–431, 2009; Ped Derm 23:81–83, 2006; Ped Derm 15:219–221, 1998; AD 117:285–289, 1981; J Cutan Dis 33:255– 260, 1915  Disorders with mutations in GJB2 (connexin 26) JID 127:2713– 2725, 2007

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

  Bart-Pumphrey syndrome    Deafness with Clouston-type phenotype    Hystrix-like ichthyosis-deafness syndrome   Non-syndromic deafness    Sensorineural hearing loss with keratoderma    Vohwinkel’s syndrome

Wiskott-Aldrich syndrome AD 136:875–880, 2000

Leiner's disease

Zunich neuroectodermal syndrome AD 132:535–541, 1996

Netherton's syndrome JAMA Derm 152:435–442, 2016; Ped Derm 31:90–94, 2014; AD 136:875–880, 2000; Ped Derm 13:183–199, 1996

TOXINS

Neuroichthyosis AD 136:875–880, 2000 Omenn syndrome (familial reticuloendotheliosis with eosinophilia) – autosomal recessive; neonatal exfoliative erythroderma, subacute combined immunodeficiency, diarrhea, hepatosplenomegaly, alopecia, failure to thrive, lymphadenopathy, elevated IgE and eosinophilia Clin Exp Dermatol 45:646–649, 2020; BJD 158:1153– 1156, 2008; AD 136:875–880, 2000 Peeling skin syndrome – type A (non-inflammatory); type B (inflammatory) – autosomal recessive; erythroderma, congenital onset, pruritus, infections; mutation in CDSN (loss of corneodesmin function); lifelong peeling of skin, recurrent skin infections, angioedema, urticarial, and asthma JID 131:779–781, 2011; Arch Dermatol Res 304:251–255, 2012; Clin Genet 86:383–386, 2014; Ped Derm 19:382–387, 2002 Restrictive dermopathy – autosomal recessive, erythroderma at birth, with extensive erosions and contractures; taut shiny skin; fetal akinesia, multiple joint contractures, dysmorphic facies with fixed open mouth, hypertelorism, pulmonary hypoplasia, bone deformities; uniformly fatal Ped Derm 19:67–72, 2002; Ped Derm 16:151–153, 1999; AD 134:577–579, 1998; AD 128:228–231, 1992 Sensorineural hearing loss, periorificial erythrokeratoderma, dental enamel defects, excess granulation tissue JID 121:1221–1223, 2003 Sjogren-Larsson syndrome – autosomal recessive; non-bullous congenital ichthyosiform erythroderma, ichthyosis with light peeling of trunk and lamellar-like ichthyosis of lower legs, yellow-brown hyperkeratosis around umbilicus, accentuated skin markings; mild to moderate mental retardation, spastic diplegia, short stature, kyphoscoliosis, retinal changes, yellow pigmentation, intertrigo – deficiency of fatty aldehyde dehydrogenase Cutis 78:61–65, 2006; Ped Derm 22:569–571, 2005; Curr Prob Derm 14:71–116, 2002; Chem Biol Interact 130–132:297–307, 2001; AD 136:875–880, 2000; Am J Hum Genet 65:1547–1560, 1999; JAAD 35:678–684, 1996; Acta Psychiatr Scand 32:1–112, 1957

X-linked ectodermal dysplasia with immunodeficiency – NEMO mutation; erythroderma, alopecia, red scaly scalp, frontal bossing, periorbital wrinkling, intertrigo, thick everted lower lip AD 144:342– 346, 2008; Curr Opin Allergy Clin Immunol 5:513–518, 2005; Immunol Rev 203:21–37, 2005; J Pediatr 114:600–602, 1989

Arsenic intoxication, acute – vesico-edematous erythroderma with small blisters or pustules BJD 149:757–762, 2003; BJD 141:1106– 1109, 1999 Boric acid poisoning Scombroid fish poisoning

ESCHARS Clinics Dermatol 37:99–108, 2019

 UTOIMMUNE DISORDERS AND DISORDERS A OF IMMUNE DYSREGULATION Antiphospholipid antibody syndrome JAAD 51:S137–142, 2004; catastrophic anti-phospholipid antibody syndrome SD Med 72:464–466, 2019 STING-associated vasculopathy with onset in infancy (SAVI) (type 1 interferonopathy) – red plaques of face and hands; chilblain-like lesions; atrophic plaques of hands, telangiectasias of cheeks, nose, chin, lips, acral violaceous plaques and acral cyanosis (livedo reticularis of feet, cheeks, and knees), distal ulcerative lesions with infarcts (necrosis of cheeks and ears), gangrene of fingers or toes with ainhum, nasal septal perforation, nail dystrophy ; small for gestational age; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis with ground glass and reticulate opacities; gain of function mutation in TMEM173 (stimulator of interferon genes); mimics granulomatosis with polyangiitis JAAD 74:186–189, 2016; JAMA Derm 151:872–877, 2015; NEJM 371:507–518, 2014

DRUGS

Tay syndrome – collodion baby Pediatrics 87:571–574, 1991

Coumadin necrosis JAAD 51:S137–142, 2004

Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – autosomal recessive; collodion baby, congenital erythroderma, sparse or absent eyelashes and eyebrows, sulfur deficient short brittle hair with tiger tail banding on polarized microscopy, trichomegaly, brittle soft nails with koilonychia, premature aging, very short stature, microcephaly, sexual immaturity, ichthyosis, photosensitivity, hypohidrosis, high arched palate, dysmyelination of white matter, bird-like facies, abnormal teeth with dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; recurrent infections with neutropenia; ocular abnormalities, osteopenia; socially engaging personality; mutation in one of 3 DNA repair genes (XPB, XPA, TTDA, or TTDN1 JAAD 63:323–328, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Am J Med Genet 35:566–573, 1990; JAAD 16:940–947, 1987; Eur J Pediatr 141:147–152, 1984

Heparin necrosis JAAD 51:S137–142, 2004 Levamisole adulterated cocaine JAAD 65:722–725, 2011 Methimazole-induced vasculitis – eschar-like leg ulcers JAMA Derm 153:223–224, 2017

DEGENERATIVE DISORDERS Neuropathic callus with underlying osteomyelitis – personal observation

INFECTIONS AND INFESTATIONS Acanthamebiasis – tender red nodules of trunk and extremities with necrosis and eschars AD 147:857–862, 2011

Eschars African tick bite fever (Rickettsia africae) (Amblyomma variegatum; A hebraeum) – hemorrhagic pustule, purpuric papules; transmitted by Amblyomma hebraeum, A. variegatum (Bont ticks) – high fever, headache, arthralgia, myalgia, malaise, fatigue, rash in 2–3 days, with eschar, widespread exanthem with maculopapules, vesicles, and pustules; purpuric plaque with ulcer of leg and back JAAD 70:959–961, 2014; AD 146:641–648, 2010; JAAD 48:S18–19, 2003Anthrax JAAD 51:S137–142, 2004

Derm 150:79–80, 2014; rhinocerebral mucormycosis J Clin Microbiol 44:892–898, 2006; J Otolarygol 34:166–171, 2005

Aspergillosis – fluctuant nodule evolving to eschar Cutis 81:127– 130, 2008; large (2–3 cm) eschar with thin erythematous halo BJD 157:407–409, 2007; AD 141:633–638, 2005; JAAD 51:S137–142, 2004; primary cutaneous aspergillosis in premature infant – necrotic eschar blanketing entire back Ped Derm 36:709–710, 2019

Orf JAAD 51:S137–142, 2004

Bacterial endocarditis – subacute, acute

Plague (Yersinia pestis) JAAD 51:S137–142, 2004

Botryomycosis – Staphylococcus aureus; disseminated papules, pustules of nose, papules of eyelids and eschars of extremities J Drugs in Dermatol 13:976–978, 2014 Boutonneuse fever JAAD 51:S137–142, 2004 Brown recluse spider bite (Loxosceles reclusa) – cyanotic pale hemorrhagic bulla progresses to eschar; sunken bluish patch JAMA Derm 150:1205–1208, 2014; JAAD 67:347–354, 2012; JAAD 51:S137–142, 2004; Loxosceles rufescens; eschar, necrosis, targetoid: 6 eyes JAMA Derm 156:203, 2020 Capnocytophaga canimorsus sepsis – dog and cat bites; necrosis with eschar; cellulitis Cutis 60:95–97, 1997; JAAD 33:1019–1029, 1995 Cat flea-associated rickettsiosis – pruritic papules of chest, abdomen, and legs; Ctenocephalides felix; fever, myalgia, malaise, headache, morbilliform eruption JAAD 75:1–16, 2016; AD 146:641– 648, 2010 Cowpox – human cowpox with fingertip eschar and arm abscess, lymphangitis, lymphadenopathy Clin Inf Dis 69:179–181, 2019 Ecthyma – eschar and ulceration JAAD 47:766–769, 2002; Streptococcus pyogenes JAMA 311:957–958, 2014 Ecthyma gangrenosum – Pseudomonas aeruginosa; Klebsiella spp., Escherichia coli, Serratia Eczema vaccinatum – small pox vaccination; vesicles, pustules, swollen face with vesicles and eschar (progressive vaccinia, vaccinia necrosum, vaccinia gangrenosum) in patients with cell mediated immune defects Cutis 101:87–90, 2018 Fournier’s gangrene – polymicrobial necrotizing fasciitis of genital or perianal skin and soft tissues after trauma or intervention Fusariosis – localized fusariosis (F. solani) – red plaque of arm with eschar AD 141:794–795, 2005; JAAD 51:S137–142, 2004 Glanders JAAD 51:S137–142, 2004 Herpes simplex virus JAAD 51:S137–142, 2004 Herpes zoster Mediterranean spotted fever – R. conorii (brown dog tick) (Rhipicephalus sanguineus); R massiliae; fever, myalgia, malaise, headache, morbilliform eruption AD 146:641–648, 2010 Melioidosis – ecthymatous eschar Clin Inf Dis 40:988–989,1053– 1054, 2005 Milker’s nodule JAAD 51:S137–142, 2004 Mucormycosis (Mucor, Rhizopus, Absidia, Apophysomyces elegans) – necrotic eschar of arm JAMA Derm 151:787–788, 2015; necrotic eschar with surrounding erythema JAAD 61:172–174, 2009; JAAD 51:S137–142, 2004; eschar of hand AD 147:235–240, 2011; violaceous hyperkeratotic plaque with central eschar JAMA

333

Mycobacterium tuberculosis – papulonecrotic tuberculid SKINmed 10:28–33, 2012 Necrotizing fasciitis JAAD 51:S137–142, 2004 N. brasiliensis – ulcerated plaque, eschar, cellulitis, sporotrichoid pattern JAMA Derm 151:895–896, 2015 Zoonotic orthopoxvirus – teats of cows as source; targetoid bullae of hands and fingers healing with eschars; edema of hands; fever; axillary lymphadenopathy NEJM 372:223–230, 2015 Phagedenic ulcer JAAD 51:S137–142, 2004 Pseudomonas aeruginosa Int J Inf Dis 17:e787, 2013 Pseudomonas oryzihabitans – due to octopus bite AD 147:963– 966, 2011 Queensland tick typhus JAAD 51:S137–142, 2004 Rat bite fever (Streptococcus moniliformis) – fever, arthritis, exanthem; papules and papulopustules of face and hand; hand and foot swellings; eschar Clin Inf Dis 60:1388,1436–1437, 2015; Ped Derm 29:767–768, 2012; JAAD 51:S137–142, 2004 Rickettsia conorii – Mediterranean spotted fever Travel Med Inf Dis 26:7–15, 2018 Rickettsia parkeri rickettsiosis – Southeastern United States; Gulf coast tick (Amblomma maculatum); eschar with surrounding petechiae, fever, lethargy, fatigue, headache, myalgia, arthralgia, morbilliform or vesiculopapular or papulopustular rash of trunk and extremities, palms and soles, and occasionally the face 0.5 to 4 days after fever; some lesions with small vesicle or pustule; morbilliform eruptions, discrete round macules and papules MMWR 65:1–44, May 13, 2016; Clin Inf Dis 59:635–642, 2014; AD 146:641–648, 2010; Clin Inf Dis 47:1188–1196, 2008 Rickettsia 364D – eschar-associated illness in California; eschar with erythema of entire forearm; Pacific coast tick (Dermacentor occidentalis) MMWR 65:1–44, May 13, 2016; Clin Inf Dis 50:541– 548, 2010 Rickettsial pox – house mouse mite bite (Liponyssodes sanguineus) (Rickettsia akari) – fever with generalized papules, vesicles, papulovesicles, crusts with ulceronecrotic plaque Ped Derm: 29:767–768, 2012; AD 146:641–648, 2010; JAAD 51:S137–142, 2004; NEJM 331:1612–1617, 1994; Clin Inf Dis 18:624–626, 1994; eschars Am J Trop Med Hyg 75:732–738, 2006 Scrub typhus (Orientia (Rickettsia) tsutsugamuchi) (larval stage of trombiculid mites (chiggers)) – headache and conjunctivitis; eschar with black crust (“cigarette burn-like: eschar); generalized macular or morbilliform rash; jaundice and abdominal pain NEJM 373:2455, 2015; Clin Inf Dis 60:1828,1864–1865, 2015; Clin Inf Dis 39:1329–1335, 2004; JAAD 51:S137–142, 2004; AD 139:1545–1552, 2003; Dtsch Med Wochenschr 123:562–566, 1998; JAAD 2:359–373, 1980; eschar and ulceration JAAD 47:766–769, 2002 Siberian typhus Snake bites – coral snakes, pit vipers, rattle snakes, cotton mouth (water moccasins), copperhead South African tick typhus JAAD 51:S137–142, 2004 Tick-borne lymphadenopathy (Rickettsia slovaca, R . rioja, R. raoultii); Dermacentor marginatus – scalp eschar with facial edema; residual alopecia JAAD 75:1–16, 2016

334 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Tick typhus (Boutonneuse fever, Kenya tick typhus, African and Indian tick typhus) (ixodid ticks) – small ulcer at site of tick bite (tache noire) – black necrotic center with red halo; pink morbilliform eruption of forearms, then generalizes, involving face, palms, and soles; may be hemorrhagic; recovery uneventful JAAD 2:359–373, 1980; eschar and ulceration JAAD 47:766–769, 2002 Trypanosoma brucei rhodiense – necrotic chancre J Clin Inf Dis 23:847–848, 1996

atopy; recurrent sinopulmonary infections JAMA Derm 151:627– 634, 2015

TRAUMA Flap necrosis

Tularemia – necrotic papule Cutis 54:279–286, 1994; eschar and ulceration NEJM 352:700–707, 2005; JAAD 51:S137–142, 2004; JAAD 47:766–769, 2002; skin slough from hamster bite MMWR 53:1202–1203, 2005

VASCULAR LESIONS

Vibrio vulnificus Epidemiol Infect 133:383–391, 2005

Buerger’s disease

Arterial emboli Atherosclerotic peripheral vascular disease Cholesterol emboli

INFILTRATIVE DISORDERS Reactive intravascular histiocytosis – black necrotic eschar of scrotum and gluteal cleft; associated with tonsillitis; possibly related to reactive angioendotheliomatosis BJD 154:560–563, 2006

METABOLIC DISORDERS

Eosinophilic granulomatosis with polyangiitis – necrotic eschar within red plaque; red papules of forehead and scalp JAAD 65:244–246, 2011 Emboli – marantic emboli Thrombotic vasculopathy

Calciphylaxis JAAD 51:S137–142, 2004

 SOPHAGEAL AND CUTANEOUS E DISEASE

NEOPLASTIC DISORDERS

JAAD 65:175–183, 2011

Angiosarcoma – ulcerated red plaque with eschar JAMA 314:1169– 1170, 2015 Lymphoma – hydroa vacciniforme-like cutaneous T-cell lymphoma (Epstein-Barr virus associated lymphoproliferative disorder), Epstein-Barr virus-related – eschars, edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, pitted scars, fever JAAD 81::534–540, 2019; JAAD 69:112–119, 2013; BJD 151:372–380, 2004; cutaneous gammadelta T-cell lymphoma; primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma; NK T-cell lymphoma, nasal type; acute necrotizing cutaneous T-cell lymphoma Clin Lymphoma Myeloma 6:146–148, 2005 Lymphomatoid papulosis Cutis 100:281,297–298, 2017; in children BJD 171:138–146, 2014

PRIMARY CUTANEOUS DISEASES Phagedenic ulcer Pityriasis lichenoides et varioliformis acuta Tropical ulcer – eschar and ulceration JAAD 47:766–769, 2002

SYNDROMES Antiphospholipid antibody syndrome PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin;

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) – esophageal candidiasis Ann Derm Venereol 141:290– 294, 2014 Bullous pemphigoid – dysphagia, odynophagia, hematemesis, esophageal strictures BJD 99:207, 1978; bullous disease of esophagus with bleeding Clin Exp Dermatol 38:274–275, 2013 CREST syndrome Dermatomyositis – dysphagia, reduced motility NEJM 370:2327– 2337, 2014 DOCK 8 deficiency – eosinophilic esophagitis Dermatol Clinics 35:11–19, 2017; J Allergy Clin Immunol 136:402–412, 2015; J Clin Immunol 35:189–196, 2015; Disease Markers 29:131–139, 2010; NEJM 361:2046–2055, 2009 Epidermolysis bullosa acquisita – dysphagia, odynophagia, heartburn BJD 172:288–290, 2015; Curr Gastroenterol Rep 4:205–212, 2000 Graft vs. host disease Dig Dis Sci 46:2292–2297, 2001 Mixed connective tissue disease – chronic reflux, Candida esophagitis, stenosis, upper GI bleed, Berrett’s esophagus (metaplasis); esophageal stenosis late effect J Med Life 9:141–143, 2016 Mucous membrane pemphigoid BJD 177:1074–1085, 2017; Obstet Gynecol 105:1188–1190, 2005; esophageal stricture Dis Esoph 17:180–182, 2004 Pemphigus vulgaris J Clin Gastroenterol 20:145–146, 1995; sloughing esophageal cast Dis Esoph e24:23–25, 2011; esophagitis dissecans superficialis; odynophagia JAMA Derm 152:948–950, 2016

Esophageal and Cutaneous Disease 335 Scleroderma – absent contractility, dilated esophagus Clin Exp Dermatol 106:82–85, 2017; Rheum 48:36–39, 2008 Sclerodermatomyositis – Gottron’s papules, periorbital erythema, Raynaud’s phenomenon, acrosteolysis, dysphagia, digital ulcers; high risk of interstitial lung disease Arthr Research Therapy 16:R111, 2014; AD 144:1351–1359, 2008; Arthr Rheum 50:565– 569, 2004; J Clin Immunol 4:40–44, 1984 Sjogren’s syndrome – dysphagia Rheum Dis Clin NA 44:143–151, 2018; J Clin Gastroenterol 46:25–30, 2012

DRUGS Antimalarials Atorvastatin – weakness, myopathy, dysphagia; statin-induced autoimmune myopathy; antibodies to HMGCR NEJM 275–283, 2019

NEOPLASTIC DISORDERS Esophageal adenocarcinoma – cutaneous metastases; cutaneous nodules Int Surg 100:558–561, 2015; Derm Online J 19:18173, 2013; Zentralbl Chir 134:481–485, 2009 Granular cell tumors – cutaneous and esophageal granular cell tumors Clin Exp Derm 35:551–552, 2010 Juvenile onset multiple gastrointestinal stromal tumors (GIST) – multiple hyperpigmented skin macules, achalasia-like stenosis of esophagus and KIT mutation Am J Surg Path 37:898–905, 2013 Kaposi’s sarcoma Mali Med 27:62–65, 2012; often asymptomatic Clin Gastr Hep 6:A202008 Leukemia Cutaneous T-cell lymphoma – CD8+CTCL Oncology Letters 5:73–75, 2013; J Clin Gastro 12:178–182, 1990 Melanoma metastases Onkologie 26:249–251, 2003

Doxycycline esophagitis – phototoxic skin eruption Gold Am J Dermatopathol 4:267–269, 1982 Methotrexate toxicity (esophagitis dessicans superficialis) – oral skin ulceration, pancytopenia, odynophagia Endoscopy 46:e99–100, 2014 Thiazides

EXOGENOUS AGENTS

PARANEOPLASTIC DISORDERS Acanthosis nigricans – esophageal cancer Z Gastroenterol 50:680–683, 2012 Bazex syndrome (acrokeratosis paraneoplastica) – squamous cell carcinoma of the esophagus; psoriasiform plaques of acral areas; ears, nose, hands, feet Radiographics 39:1411–1434, 2019; An Bras Derm 88(Suppl 1) 209–211, 2013

Cyanamide (calcium carbamide) JAAD 23:1168–1169, 1990

Howell-Evans syndrome (tylosis) – palmoplantar keratoderma; squamous cell cancer of the esophagus with oral leukoplakia Cancer 72:17–19, 1993

INFECTIONS AND INFESTATIONS

Paraneoplastic pemphigus – esophageal erosions JAAD 77:795– 806, 2017s

Bacillary angiomatosis Indian J Surg Pathol 11:241–244, 2013 Candidiasis, including mucocutaneous candidiasis and HIV disease Chagas’ disease GI Endoscophy 24:122, 1978 Herpes simplex virus infection – herpes esophagitis Cutis 95:44–46, 2015

PRIMARY CUTANEOUS DISEASES Atopic dermatitis and eosinophilic esophagitis JAAD 76:559–560, 2017 Darier’s disease Indian J Dent Res 22:843–846, 2011 Epidermolysis bullosa, recessive dystrophic – esophageal stricture

INFLAMMATORY DISORDERS Amyloidosis, primary systemic; dilated atonic esophagus; Am J Gastroenterol 103:776–777, 2008; dysphagia, esophageal ulcerations BMJ Case Rep Oct 21, 2018 Crohn’s disease – esophageal punctate or slit-like ulcers with surrounding mound of edema, strictures, ulcers, thickened folds, sinus tracts, fistulas; cobblestoned mucosa Interstitial granulomatous dermatitis and arthritis and esophageal cancer Clin Exp Derm 38:501–503, 2013 Stevens-Johnson syndrome Dig Dis Sci 46:2292–2297, 2001 Toxic epidermal necrolysis Am J Surg Pathol 24:1678–1682, 2000; esophageal stricture Conn Med 77:541–544, 2013

METABOLIC DISORDERS Iron deficiency – oral aphthae NEJM 369:265–274, 2013; JAAD 52:500–508, 2005; Plummer-Vinson syndrome (post-cricoid esophageal web); atrophic glossitis, koilonychia Arch Int Med 155:2008–2010, 1995

Epidermolysis bullosa – esophageal stenosis, dysphagia BMC Gastro 13:47, 2018 Hailey-Hailey disease BJD 182:1294–1295, 2019; Curr Gastroenterol Rep 4:205–212, 2000; AD 109:718–719, 1974 Lichen planus, erosive JAAD 21:1076–1080, 1989; vulvo-vaginalgingival syndrome (erosive lichen planus) JAAD 55:98–113, 2006; Int J Derm 28:381–384, 1989; nail degloving JAAD 58:232–237, 2008; esophageal stricture, dysphagia, odynophagia, esophageal squamous cell carcinoma JAAD 65:175–183, 2011 Lichen sclerosus et atrophicus Palmoplantar keratoderma with transepidermal elimination with oral florid papillomatosis and leukoplakia of the esophagus J Dermatol 21:974–978, 1994 Raspberry-like papillomas on lips, perineum, fingers, toes, buccal mucosa and esophagus Cutis 53:309–312, 1994

SYNDROMES Behcet’s disease Dig Dis Sci 54:201–207, 2009; Dig Dis Sci 46:2292–2297, 2001; rare esophageal ulcerations World Gastroenterol 21:3801–3812, 2015

336 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Blue rubber bleb nevus syndrome – polypoid mucosal or submucosal masses; sclerotic fibromas, oral papillomas, blue, purple or black compressible papules or nodules Radiographics 39:1411–1434, 2019 Cowden’s syndrome – glycogenic acanthosis of esophagus; nodular appearing esophagus with small uniform round or oval discrete mucosal plaques or nodules Radiographics 39:1411–1434, 2019; J Natl Cancer Ins 115:1607–1616, 2013 Dyskeratosis congenita – esophageal stenosis JAAD 77:1194– 1196, 2017; J Blood Med 5:157–167, 2014; Br J Haematol 145:164–172, 2009; Semin Cut Med Surg 16:72–80, 1997

EXANTHEM  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – clothing; poison ivy; systemic contact dermatitis (ingestion of previously skin-sensitized allergen) (baboon syndrome) – dermatitis of buttocks, anogenital areas, flexures, and eyelids – mercury Ped Derm 21:250–253, 2004; Contact Dermatitis 10:97–100, 1984; systematized allergic contact dermatitis to aspartame in montelukast tablets Ped Derm 26:739–743, 2009

Ehlers-Danlos syndrome type IV – spontaneous rupture of the esophagus Eur J Surg 164:313–316, 1998

Anaphylaxis – generalized erythema

Escobar syndrome – facial dysmorphism, multiple webbing (pterygia); congenital contractures (arthrogryposis); esophageal atresia Genet Couns 25:321–330, 2015

Autoprogesterone dermatitis

Goltz’s syndrome – HPV-negative papillomatosis of esophagus Gastro 140:784, 2011 Hereditary hemorrhagic telangiectasia Gastro 91:1079–1083, 1986 Hereditary mucoepithelial dysplasia (dyskeratosis) (Gap junction disease, Witkop disease) – autosomal dominant; esophageal stenosis; non-­scarring alopecia; dry rough skin; red eyes, non-scarring alopecia, follicular keratosis (keratosis pilaris), erythema of oral (hard palate, gingival, tongue) and nasal mucous membranes, cervix, vagina, and urethra; perineal and perigenital psoriasiform dermatitis (perineal erythema); hyperpigmented hyperkeratotic lesions of flexures (neck, antecubital and popliteal fossae); keratitis (visual impairment) increased risk of infections, fibrocystic lung disease Ped Derm 29:311–315, 2012; BJD 153:310–318, 2005; Ped Derm 11:133–138, 1994; Am J Med Genet 39:338–341, 1991; JAAD 21:351–357, 1989; Am J Hum Genet 31:414–427, 1979; Oral Surg Oral Med Oral Pathol 46:645–657, 1978 Hyper IgE syndrome – esophageal reflux and dysmotility, triad of recurrent furuncles, cyst-forming pneumonia, and extreme elevations of IgE; dermatitis; skeletal abnormalities Kindler’s syndrome – esophageal stenosis/stricture An Bras Derm 88(Suppl1) 212–52103 Lipoid proteinosis – verrucous waxy hyperpigmented plaques and nodules on elbows, knees, dorsal fingers; multiple yellow nodules throughout esophagus, stomach, duodenum, colon Case Reports Med 2014:952038 Multicentric reticulohistiocytosis Clin Rheum 12:252–254, 2006 Myotonic dystrophy (Steinert syndrome) type 1 – autosomal dominant; muscular hypotonia, distal weakness of muscles, frontal alopecia, cataract, sensorineural hearing loss, dysarthria, dysphagia, diabetes mellitus, hypothyroidism, cardiac arrhythmias Dtsch Arztebl Int 116:489–496, 2019; J Med Genet 19:341–348, 1982 Peeling skin syndrome – type A (non-inflammatory); type B (inflammatory) – autosomal recessive; eosinophilic esophagitis; dilated cardiomyopathy; erythroderma, congenital onset, pruritus, infections; mutation in CDSN (loss of corneodesmin function); lifelong peeling of skin, recurrent skin infections, angioedema, urticaria, and asthma JID 131:779–781, 2011; Arch Dermatol Res 304:251–255, 2012; Clin Genet 86:383–386, 2014; Ped Derm 19:382–387, 2002 Plummer-Vinson syndrome – post-cricoid esophageal webs

VASCULAR DISORDERS PHACES syndrome – dysphagia Ped Derm 32:64–69, 2015

Autoeczematization reaction Bullous pemphigoid – urticarial, non-bullous pemphigoid JAAD 78:989–995, 2018; childhood vesicular pemphigoid Cutis 83:182– 184, 2009 C3 deficiency – morbilliform eruption demonstrating leukocytoclastic vasculitis Pediatrics 71:81–87, 1983 CD4 lymphopenia BJD 178:335–349, 2018 Common variable immunodeficiency – papulonodular eruption JAAD 44:710–713, 2001 Cutaneous eruption of lymphocyte recovery – morbilliform eruption at 14–21 days after graft AD 125:1512–1517, 1989 Dermatomyositis – dermatomyositis with hydroxychloroquine AD 138:1231–1233, 2002 Dermatophytids – associated with kerion; widespread eruption; follicular papules occasionally with keratotic spines J Dermatol 21:31–34, 1994 DiGeorge's syndrome – morbilliform exanthem; developmental defects of 3rd and 4th pharyngeal pouches, congenital thymic aplasia, autosomal dominant or sporadic, neonatal tetany due to absence of parathyroids, cardiac anomalies (truncus arteriosus), short philtrum, low-set malformed ears, hypertelorism, increased susceptibility to Candida, viral, and Pneumocystis carinii infections, loss of portion of proximal long arm of chromosome 22, may be same as velocardiofacial syndrome Familial cold autoinflammatory syndrome (cold urticaria) BJD 150:1029–1031, 2004 Fogo selvagem N Bras Dermatol 93:638–650, 2018 Graft vs. host disease, adult; acute – macular erythema starts on face, neck and shoulders, then becomes generalized; may start on palms, soles, and ears JAAD 49:1081–1085, 2003; morbilliform eruption JAAD 66:515–532, 2012; may become lichenoid or bullous; or chronic AD 132:1161–1163, 1996; JAAD 38:369–392, 1998; AD 134:602– 612, 1998; AD 126:1324–1329, 1990; acute GVHD associated with reactivation of HHV6 JAAD 58:802–809, 2008; infant with severe combined immunodeficiency disease; diffuse blanching erythema Hyper IgD syndrome – macular, papular, nodular, and urticarial eruptions Ann Dermatol Venereol 123:314–321, 1996; reticulated erythematous exanthem – IgD with arthritis AD 148:17–20, 2012 IL2 deficiency BJD 178:335–349, 2018 IL2R mutations BJD 178:335–349, 2018 Linear IgA disease – mimicking Stevens-Johnson syndrome with targetoid lesion BJD 178:786–789, 2018; Dermatol Clinics 4:89–98, 1986 Lupus erythematosus – systemic lupus erythematosus BJD 135:355–362, 1996; discoid lupus; papulonodular mucinosis JAAD

Exanthem 337 32:199–205, 1995; AD 114:432–435, 1978; subacute cutaneous lupus Am J Clin Dermatol 10:366–381, 2009

Checkpoint inhibitors – morbilliform eruptions JAAD 80:990–997, 2019

Pemphigus vulgaris

Chemotherapy-induced eccrine squamous syringometaplasia Soc Ped Derm Annual Meeting, July 2005; AD 132:873–878, 1997

Pemphigus foliaceus Ped Derm 36:236–241, 2019 Pemphigus – IgA pemphigus, subcorneal pustular dermatosis type JAAD 53:541–543, 2005 Rheumatoid arthritis – maculopapular erythema BJD 147:905–913, 2002 Scleroderma, including CREST syndrome Serum sickness Severe combined immunodeficiency syndrome – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn (3 weeks); erythroderma, seborrheic dermatitis-like eruption; morbilliform eruptions, lichen planus-like eruptions, dermatitis; mutations in cytokine common gamma chain, JAK3, RAG1 or RAG2, IL-7Rgamma, adenosine deaminase BJD 178:335–349, 2018; JAAD 66:292–311, 2012; Ped Derm 26:213–214, 2009; AD 144:342–346, 2008; Dermatol Therapy 18:176–183, 2005; Ped Derm 17:91–96, 2000; AD 136:875–880, 2000; J Pediatr 123:564– 572, 1993; Ped Derm 8:314–321, 1991 Still's disease (juvenile rheumatoid arthritis), including neonatal exanthem in JRA BJD 145:187–188, 2001; J Pediatr 137:128–131, 2000; adult Still’s disease – pruritic facial erythematous rash; dirty brown hyperkeratotic exanthema of face, chest, abdomen, postauricular areas JAAD 73:294–303, 2015; Medicine 70:118–136, 1991; adult Still’s disease – personal observation

Cladribine – morbilliform eruption JAAD 71:203–214, 2014 Clopidogrel – morbilliform eruption; angioedema Curr Allergy Asthma Rep 11:52–57, 2011 Contrast media Clin Exp Dermatol 44:844–860, 2019 CTLA-4 inhibitors – ipilimumab, tremelimumab – vitiligo, morbilliform eruption JAAD 72:221–236, 2015 Cytarabine – purpuric intertriginous plaques, scalp involvement, papules coalesce into papular purpuric violaceous generalized exanthema, red knee, red feet JAAD 73:821–828, 2015 Dactinomycin – flexural cutaneous necrosis with post-inflammatory hyperpigmentation; morbilliform, macular desquamative dermatitis, brawny erythema AD 142:1660–1661, 2006 Drug-induced diffuse erythema – multiple drugs ddC JAAD 21:1213, 1217, 1989 Pegylated liposomal doxorubicin – red hands and feet (acral erythrodysesthesia); follicular exanthema, intertrigo, alopecia, nail changes, stomatitis BJD 176:507–509, 2017

X-linked agammaglobulinemia – dermatomyositis-like eruption

Drug reaction with eosinophilia and systemic symptoms (DRESS) – morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, urticarial papular-confluent; facial edema, lymphadenopathy Ped Derm 36:324–329, 2019; Cutis 102:322–326, 2018; JAMA Derm 152:1254–1257, 2016; BJD 170:866–873, 2014; JAAD 68:E1–14BJD 169:1071–1080, 2013; BJD 168:391–401, 2013; Am J Med 124:588–597, 2011; Ped Derm 28:741–743, 2011; JAAD 68:693–705, 2013; AD 146:1373–1379, 2010; NEJM 242:897–898, 1950

CONGENITAL DISORDERS

Everolimus – mTOR inhibitor; broad red patches of face, scalp, upper trunk; also widespread dermatitis, acneiform eruptions The Dermatologist July 2015; pp.47–48

TRAPS (TNF receptor associated periodic fever syndrome) BJD 178:335–349, 2018 Urticaria – acute; idiopathic, foods, drugs, hymenoptera stings, plasma expanders, blood products, anesthetic agents Cutis 79:41–49, 2007;

Erythema toxicum neonatorum – blotchy macular erythema (one to several hundred lesions); surmounted by pustules Ped Derm 24:474–482, 2007 Post-maturity desquamation

Fixed drug eruption – lamotrigine BJD 144:1289–1291, 2001 Fludarabine – morbilliform eruption JAAD 71:203–214, 2014 Foscarnet – urticarial rash with or without exanthema; eosinophilic pustular folliculitis JAAD 44:546–547, 2001 G-CSF – papular exanthem Ped Derm 17:205–207, 2000

DRUG-INDUCED Acetaminophen – exanthem of breasts Cutis 89:284–286, 2012 Acute generalized exanthematous pustulosis – multiple drugs Semin Cutan Med Surg 15:244–249, 1996 Ampicillin in infectious mononucleosis JAAD 72:1–19, 2015 Autologous peripheral blood stem cell transplantation – flexural erythematous eruption BJD 145:490–495, 2001 Azathioprine hypersensitivity reaction – occurs within first four weeks of treatment; fever, malaise, arthralgias, myalgias, nausea, vomiting, diarrhea; morbilliform eruption, leukocytoclastic vasculitis, acute generalized exanthematous pustulosis, erythema nodosum, Sweet’s syndrome Clin Inf Dis 68:1427–1430, 2019; JAAD 65:184–191, 2011

GM-CSF AD 127:49–52, 1991 Guanfacine – lichenoid eruption Ped Derm 31:614–615, 2014 IL-2 reaction JAMA 258:1624–1629, 1987 Imatinib (signal transduction inhibitor) – exanthem Imatinib/ dasatinib/nilotinib (tyrosine kinase inhibitors) – morbilliform eruptions JAAD 71:217–227, 2014; JAAD 58:545–570, 2008 Immune checkpoint inhibitors – CTLA-4, PD-1/PD-L1 inhibitors – morbilliform eruptions Clin in Dermatol 38:94–104, 2020 Influenza vaccine – widespread lichenoid eruption J Drugs Dermatol 13:873–875, 2014; generalized lichen planus J Drugs Dermatol 6:536–538, 2007 Iododerma Australas J Dermatol 28:119–122, 1987 Ipilimumab – morbilliform exanthem JAAD 71:161–169, 2014

BCG vaccination – morbilliform or purpuric eruptions with arthralgia, abdominal pain BJD 75:181–192, 1963; lichenoid and red papules and papulopustules Ped Derm 13:451–454, 1996

Jarisch-Herxheimer reaction – treatment of syphilis, onchocerciasis, Lyme disease, strongyloidiasis AD 125:77–81, 1989; Hautarzt 35:588–590, 1984

Bortezomib (proteosome inhibitor) – vasculitis presenting as morbilliform exanthema JAAD 58:545–570, 2008

Kit and BCR-ABL inhibitors – imatinib, nilotinib, dasatinib – facial edema morbilliform eruptions, pigmentary changes, lichenoid reactions, psoriasis, pityriasis rosea, pustular eruptions, DRESS,

338 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Stevens-Johnson syndrome, urticarial, neutrophilic dermatoses, photosensitivity, pseudolymphoma, porphyria cutanea tarda, small vessel vasculitis, panniculitis, perforating folliculitis, erythroderma JAAD 72:203–218, 2015 Leuprolide acetate – generalized papular eruption J Drugs Dermatol 13:755–757, 2014 Lupus erythematosus – subacute cutaneous lupus erythematosus  Mitotane JAMA Derm 152:109–111, 2016   Beta blockers   Calcium channel blockers   Chemotherapeutic agents  Diuretics  Immunomodulators MEK inhibitors – C1-1040, selumetinib, trametinib – morbilliform eruptions, papulopustular eruptions, xerosis, paronychia JAAD 72:221–236, 2015 Methotrexate – papular eruption in patients with rheumatic diseases JAAD 40:702–707, 1999 Morbilliform drug eruption – multiple drugs SKINmed 10:373–383, 2012 mTOR inhibitors – rapamycin, everolimus, temsirolimus – stomatitis, rash JAAD 72:221–236, 2015 Nevirapine (non-nucleoside reverse transcriptase inhibitor) – morbilliform eruptions JAAD 63:549–561, 2010 Non-pigmenting fixed drug eruption BJD 118:827–829, 1988 Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015 Pegfilgrastim (long-acting G-CSF) BJD 161:717–719, 2009 Pembrolizumab – hypopigmentation, pruritus, morbilliform eruptions, photosensitivity JAMA Derm 151:1206–1212, 2015 Pemetrexed – morbilliform eruption JAAD 71:203–214, 2014 Prednisone JAAD 790–793, 1998 Pseudolymphoma – drug-induced pseudolymphoma syndrome including cutaneous pseudolymphoma syndrome due to carbamazepine JAAD 38:806–809, 1998; JAAD 38:877–905, 1998 Radiocontrast material – persistent erythema RAF inhibitors (MAPK pathway) – vemurafenib and dabrafenib – exanthema warts and other hyperkeratotic lesions, keratoacanthomas, squamous cell carcinoma, melanocytic nevi, keratosis pilaris, seborrheic dermatitis, hyperkeratotic hand-foot reactions, photosensitivity, panniculitis with arthralgias, alopecia JAAD 72:221–236, 2015 Simvastatin – urticarial vasculitis Dermatitis 21:223–224, 2010 Sorafenib – exanthema and desquamation JAAD 60:299–305, 2009 Suramin AD 128:75–79, 1992 Telaprevir dermatitis – morbilliform eruption JAMA Derm 150:756– 759, 2014; JAMA Derm 149:152–158, 2013; DRESS J Drugs in Dermatol 13:199–200, 2014 Trametinib – morbilliform eruptions JAAD 71:217–227, 2014 Vancomycin – morbilliform eruption due to linear IgA bullous dermatosis AD 144:774–778, 2008

Vemurafenib – erythematous eruption with spiny keratosis pilaris; erythema and edema of face and neck BJD 169:934–938, 2013; DRESS JAMA Derm 149:1242–1243, 2013; morbilliform eruptions BJD 173:1024–1031, 2015; JAMA Derm 151:1103–1109, 2015; AD 148:357–361, 2012; palmoplantar hyperkeratosis JAAD 67:1265– 1272, 2012 Vincristine/vinblastine/vinorelbine – morbilliform eruptions JAAD 71:203–214, 2014

EXOGENOUS AGENTS Aniline-contaminated rape seed oil (denatured with aniline) (Spanish toxic oil syndrome) – early see pruritic morbilliform exanthem followed by cutaneous sclerosis JAAD 18:313–324, 1988; JAAD 9:159–160, 1983; cutaneous mucinosis of arms, thighs, and lower legs JAAD 16:139–140, 1987 Baboon syndrome – acute exanthem of anogenital region, buttocks, and flexural extremities; amoxicillin, ampicillin, heparin, mercury, nickel, food additives Levamisole-contaminated cocaine – morbilliform exanthem Clin Inf Dis 61:1840–1849, 2015 Rhus – ingestion of Rhus as folk medicine remedy; morbilliform eruption BJD 142:937–942, 2000

INFECTIONS AND INFESTATIONS Adenovirus – fatal disseminated adenovirus in patient with stem cell transplant – follicular papules with keratotic papules of palms and soles BJD 174:885–888, 2016; age 6 months to 5 years; morbilliform, rubelliform, or petechial eruptions Tyring, p.203, 2002 African tick bite fever (Rickettsia africae) – hemorrhagic pustule, purpuric papules; transmitted by Amblyomma hebraeum, A. variegatum (Bont ticks) – high fever, headache, arthralgia, myalgia, malaise, fatigue, rash in 2–3 days, with eschar, widespread exanthem with maculopapules, vesicles, and pustules JAAD 70:959–961, 2014; AD 146:641–648, 2010; JAAD 48:S18–19, 2003 Alphavirus/flavivirus/bunyavirus Anthrax Arcanobacterium haemolyticum – mono-like syndrome; exanthem and pharyngitis AD 132:61–64, 1996; Clin Inf Dis 21:177–181, 1995; annular urticarial lesions JAAD 48:298–299, 2003; scarlet fever-like rash with pharyngitis Skin and Allergy News; page 34, November 2009 Arena virus hemorrhagic fevers, including lassa fever Aspergillosis (disseminated) – morbilliform rash which becomes pustular Ped Derm 19:439–444, 2002 Bartonella quintana – urban trench fever; body louse; transient truncal morbilliform rash Clin Inf Dis 31:131–135, 2000; Bull WHO 35:155–164, 1996 Bartonellosis (Bartonella bacilliformis) – 1–4mm pruritic red papules Clin Inf Dis 33:772–779, 2001 BCG infection, disseminated – patchy erythema Ped Derm 17:208–212, 2000; disseminated BCG in X-linked severe combined immunodeficiency Ped Derm 23:560–563, 2006 Black widow spider bite – lactrodectism; pruritus, urticarial, diaphoresis, severe muscle cramping, joint stiffness, headache, nausea, vomiting Am J Emerg Med 30:836e1–2, 2012

Exanthem 339 Boutonneuse fever – Rickettsia conorii; diffuse morbilliform eruption; petechiae; palms and soles involved JAAD 49:363–392, 2003

A6 – generalized vesicular exanthema with flexural vesicles; acral purpuric macules of palms and soles Ped Derm 33:429–437, 2016

Bristle worm dermatitis (marine) – rash and edema JAAD 61:733– 750, 2009

Coxsackie virus A 4, 5, 6, 9, 16 B5, B1–6 – macular; Coxsackie A4 – widespread vesicular eruption Pediatrics 41:873–882, 1968;

Brown recluse spider bite – morbilliform eruption JAAD 55:888–890, 2006; JAAD 52:S53, 2005; Cutis 74:341–347, 2004; Rev Inst Med Trop Sao Paolo 44:139–143, 2002; J Fam Pract 48:536–542, 1999; purpuric morbilliform eruption in children at 24–48 hours JAAD 44:561–573, 2001; JAAD 44:599–602, 2001

Coxsackie A 5, 16 – hand, foot, and mouth disease – vesicular;

Brucellosis – morbilliform, scarlatiniform, disseminated papulonodular, bullous, hemorrhagic eruptions Cutis 63:25–27, 1999; AD 117:40–42, 1981

Cryptococcosis Am J med Sci 308:1925, 1994

Campylobacter jejuni – in X-linked agammaglobulinemia J Clin Inf Dis 23:526–531, 1996 Candidiasis – including congenital cutaneous candidiasis JAAD 37:817–823, 1997 Candida parapsilosis – personal observation Capnocytophaga canimorsus sepsis – dog and cat bites; necrosis with eschar; macular and morbilliform eruptions Cutis 60:95–97, 1997; Eur J. Epidemiology 12(5) 521–533, 1996; JAAD 33:1019– 1029, 1995 Cat scratch disease – morbilliform eruption JAAD 41:833–836, 1999; JAAD 31:535–556, 1994; JAAD 18:239–259, 1988; Ped Derm 5:1–9, 1988 Cercarial dermatitis – schistosomes; pruritic red papules; fresh water avian cercarial dermatitis (swimmer’s itch) Cutis 19:461–467, 1977; sea water avian cercarial dermatitis Bull Marine Sci Gulf Coast 2:346–348, 1952; fresh water mammalian cercarial dermatitis Trans R Soc Trop Med Hyg 66:21–24, 1972 Chagas’ disease – schizotripanides (exanthems) JAAD 60:897–925, 2009; fever and rash following cardiac transplantation NEJM 380:2564–2573, 2019 Cheyletiella infestation Chikungunya fever – morbilliform exanthem of trunk and limbs with islands of sparing; high fever, headache, photophobia, myalgia, arthralgias Ped Derm 35:408–409, 2018; NEJM 372:1657–1664, 2015; JAMA Derm 151:257–258, 2015 Coccidioidomycosis – acute pulmonary coccidioidomycosis – macular, papular, urticarial, morbilliform, and targetoid lesions of exanthem JAAD 75:1–16, 2016; NEJM 363:2046–2054, 2010; JAAD 55:929, 942, 2006; AD 142:744–746, 2006; macular red rash in 10% Am Rev Resp Dis 117:559–585; 727–771, 1978; morbilliform toxic erythema Dermatol Clin 7:227–239, 1989; hypersensitivity reaction in primary pulmonary coccidioidomycosis JAAD 46:743– 747, 2002 Chlamydia pneumonia – MIRM-like syndrome with cheilitis, penile erosions, morbilliform eruption Ped Derm 34:465–472, 2017 Colorado tick fever – Orbivirus; macules, papules, morbilliform eruption, petechiae JAAD 49:363–392, 2003 Corynebacterium hemolyticum – pharyngitis and scarlatiniform rash Ann Int Med 105:867–72, 1986 Covid-19 infection – varicella-like exanthem JAAD 83:280–285, 2020; urticarial, morbilliform, papular exanthems – personal observation Cowpox BJD 153:451–453, 2005 Coxsackie virus A1–A24, B1–B6 (enterovirus) – most common summertime viral skin exanthem Skin and Allergy News 30:38, 1999; Coxsackie A 4, 5, 6, 9, 16 and B5 – macular exanthem Tyring, p.3, 2002; Coxsackie A 2, 4, 7, 9; B1, 2, 3, 4, 5, 6 – morbilliform A9,16,B5 – sparse papulovesicular exanthem AD 139:1545–1552, 2003; Coxsackie B5 exanthem – personal observation; Coxsackie

Coxsackie A 5, 9, 10, 16 – maculopapular-vesicular; Coxsackie A9 – urticarial; Coxsackie A16 – Gianotti-Crosti-like rash JAAD 6:862–866, 1982; Coxsackie B5 – morbilliform Am J Med Sci 251:141–158, 1966 Cytomegalovirus – morbilliform, scarlatiniform eruptions Dermatology 200:189–195, 2000; papular, purpuric, vesiculobullous lesions with indurated pigmented nodules or plaques JAAD 24:860–867, 1991;JAAD 18:1333–1338, 1988; rubella-like or measles-like exanthems BJD 144:203–205, 2001; Ann Med Interne 152:227–235, 2001; CMV mononucleosis with ampicillin-induced rash; congenital – blueberry muffin (violaceous-magenta macules) baby (extramedullary hematopoiesis) NEJM 362, 833, 2010 Dengue fever (Flavivirus) – morbilliform or scarlatiniform eruption (classic dengue fever) – initially (first 24 hours) flushing of face, neck, and chest; morbilliform or macular eruption with white islands of sparing and petechiae; eruption on day 3–4, then becomes petechial; acral and/or periorbital edema, petechial mucosae, severe headache, fever, retroorbital pain, joint and bone pain with severe backache, arthralgia, myalgia, leukopenia; absence of sore throat and cough; conjunctival hemorrhages, palmar edema and erythema; abdominal pain; platelet count under 240,000; incubation period 3–14 days; Aedes aegypti/A. albopictus JAAD 75:1–16, 2016; Dermatol Clinics 29:33–38, 2011; Am J trop Med Hyg 82:922, 2010; JAAD 58:308–316, 2008; JAAD 46:430–433, 2002; Tyring, p.477, 2002; Dermatol Clinics 17:29–40, 1999; Inf Dis Clin NA 8:107, 1994; Bull Soc Pathol Exot 86:7–11, 1993; exanthem with islands of sparing (“white islands in a sea of red”) Clin Inf Dis 36:1004–1005, 1074–1075, 2003; locally acquired dengue from Key West, Florida MMWR 59:577–581, 2010; clinical differential diagnosis includes typhoid fever, leptospirosis, meningococcal disease, streptococcal disease, staph, rickettsial disease, malaria, arbovirus (chikungunya, o’nyong nyong fevers), Kawasaki’s disease Dermatophytid Acta DV 74:403–404, 1994 Dermatophytosis, generalized Ebola virus hemorrhagic fever (Filovirus) – exanthem which becomes purpuric with desquamation of palms and soles JAAD 65:1213–1218, 2011; MMWR 44, No.19, 382, 1995 Echovirus 1–34 (enterovirus) (esp 6 and 9) – morbilliform eruption 2,4,6,9,11,16,18 – macular exanthem Echovirus 9 and 16 – sparse papulovesicular exanthem AD 139:1545–1552, 2003 rubelliform and morbilliform eruptions Pediatrics 26:12–26, 1960; Echovirus 16 – Boston eruption JAMA 155:544–548, 1954; Echovirus 2 – rubelliform Am J Hyg 79:64–73, 1964; Echovirus 11,19 – petechial rash Arch Dis Child 57:22–29, 1982; Echovirus 6,11,25 – morbilliform rash J Infect 6:67–70, 1983; Echovirus 23,32 – telangiectatic macular lesions Pediatrics 44:498–502, 1969; Echovirus 19 – punctate macular rash in infants Arch Dis Child 51:631–633, 1976; Echovirus 11 – vesicular rash AD 113:1705–1706, 1977; 2-rubellalike; 4, 9, 11 – maculopapular-vesicular; 11,19 – petechial rash; 6, 9, 11, 25 – morbilliform rash; 19 – punctate macular; 23 and 3 – telangiectatic macular rash Eczema vaccinatum – sparse papulovesicular exanthem AD 139:1545–1552, 2003 Ehrlichiosis – morbilliform and petechial eruptions in human monocytic ehrlichiosis; rash very uncommon in human granulocytic ehrlichiosis (Anaplasma phagocytophilum) J Pediatr 120:998–1000, 1992; Ehrlichia chaffeensis; E. ewingii (human monocytic ehrlichio-

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sis) (Amblyomma americanum) – diffusely erythematous or morbilliform, scattered petechiae or macules Clin Inf Dis 33:1586– 1594, 2001; E equi, E. phagocytophila (human granulocytic ehrlichiosis) (Ixodes scapularis, Dermacentor variabilis, I. pacificus) – petechia, macules, papules JAAD 49:363–392, 2003

Hepatitis B – macular, morbilliform, or lichenoid eruptions; morbilliform exanthem JAAD 8:539–548, 1983; serum sickness – reticulated fine red blanching erythema; fever, myalgias, arthritis NEJM 368:1239–1245, 2013

Emmonsia pasteuriana – dimorphic fungus; disseminated infection in South Africa; lichenoid diffuse papulosquamous eruption; crusted verrucous facial nodules and plaques NEJM 369:1416–1424, 2013

Hepatitis virus G Lancet 1:1065, 1988; NEJM 329:156–161, 168–171, 1973

Endemic typhus (murine typhus) (Rickettsia mooseri) (Oriental rat flea (Xenopsylla cheopis)) – macular or morbilliform eruption of trunk resembling epidemic typhus with no purpura and low mortality Cutis 86:282–284, 2010; JAAD 2:359–373, 1980 Epidemic typhus (Rickettsia prowazekii) – morbilliform eruption becomes petechial exanthema; fever, nausea, diarrhea, delirium, respiratory failure, shock JAAD 82:551–569, 2020 Enterovirus infections – include poliovirus, coxsackie viruses A and B, and echoviruses Enterovirus 68–95 Skin and Allergy News 30:38,1999; enterovirus 71 Epidemic typhus (Rickettsia prowazeki) (body louse) – pink macules on sides of trunk, spreads centrifugally; flushed face with injected conjunctivae; then rash becomes deeper red, then purpuric; gangrene of finger, toes, genitalia, nose JAAD 2:359–373, 1980; transient red rash of trunk and face Clin Inf Dis 32:979–982, 2001; Brill-Zinsser disease – recrudescence of epidemic typhus Epidermodysplasia verruciformis- – acquired epidermodysplasia verruciformis in HIV disease – lichenoid hyperpigmented, pink flat warts, tinea versicolor-like Dermatol Surg 39:974–980, 2013; Clin Inf Dis 54:e119–123, 2012; AD 148:128–130, 2012; AD 147:590– 596, 2011; JAAD 60:315–320, 2009; AD 131:1312–8, 1995; Arch Dermatol Syphilol 141:193–203, 1922 Epstein_Barr virus infectious mononucleosis – morbilliform, purpuric, or macular exanthem JAAD 72:1–19, 2015; Clin Inf Dis 59:95,136–137, 2014; NEJM 362:1993–2000, 2010; JAAD 58:308–316, 2008; sparse papulovesicular exanthem AD 139:1545– 1552, 2003; urticarial, vesicular, bullous, petechial and purpuric exanthems; ampicillin-associated morbilliform or scarlatiniform rash erythema multiforme following mononucleosis – personal observation Fever with widespread purpuric exanthema Clin Inf Dis 59:95, 136–137, 2014 Erysipelothrix rhusiopathiae in neonate – erythema multiforme-like exanthem J Clin Inf Dis 24:511, 1997 Filoviruses – Marburg and Ebola virus; transient morbilliform rashes, purpura, red eyes JAAD 49:979–1000, 2003 Folliculitis Gianotti-Crosti syndrome – papular acrodermatitis of childhood; papules of buttocks and thighs, then extensor arms, then face JAAD 65:876–877, 2011; JAAD 54:136–145, 2006; Ped Derm 21:542– 547, 2004; Cutis 67:291–294, 2001; JAAD 26:207–210, 1992; AD 120:891–896, 1984; G Ital Dermatol 96:678, 1955 Gonococcemia – sparse papulovesicular exanthem AD 139:1545– 1552, 2003 H1N1 influenza A – morbilliform exanthema of thighs, lower legs, and dorsal feet AD 146:101–102, 2010 Hand foot and mouth disease – Coxsackie A16, A5, A7, A9, A10, B2, B3, B5, enterovirus 7; exanthem Ped Inf Dis 33:e92–98, 2014; Ped Derm 20:52–56, 2003 Hepatitis A – rash Ann DV 110:647–654, 1983; or B – urticarial

Hepatitis C – morbilliform eruption J Cut Med Surg 12:71–76, 2008

Herpes B virus – secondary papular eruptions Herpes simplex virus – eczema herpeticum (Kaposi’s varicelliform eruption) Cutis 73:115–122, 2004; Arch Dis Child 60:338–343, 1985; Kaposi’s varicelliform eruption associated with Grover’s disease JAAD 49:914–915, 2003; herpes simplex virus-associated exanthem following stem cell transplantation AD 144:902–907, 2008 Herpes zoster, disseminated HHV-6 reactivation in chronic graft vs. host disease – morbilliform eruption, fever, diarrhea JAAD 72:696–702, 2015; Lancet 1:1065, 1988 HIV – AIDS; acute HIV – fever, fatigue, headache, myalgia, lymphadenopathy, pruritic papular eruption of AIDS; firm discrete red, hyperpigmented urticarial papules of trunk and upper arms JAAD 58:308–316, 2008; JAMA 292:2614–2621, 2004; generalized skin-colored papules and nodules Int J Derm 32:784–789, 1993; morbilliform eruption – acute HIV infection – erythematous macules, morbilliform eruptions on trunk and face, also palms and soles with arthralgias; generalized seborrheic dermatitis AD 138:117–122, 2002; JAAD 28:167–173, 1993; AD 134:1279–1284, 1998; Kawasaki-like syndrome Clin Inf Dis 32:1628–1634, 2001; pruritic papular eruption with HIV in Uganda JAMA 292:2614–2621, 2004 Histoplasmosis (disseminated) in AIDS – morbilliform rash with scale Cutis 55:161–164, 1995; AD 121:1455–1460, 1985; Am J Med 64:923, 1978; id reaction JAAD 48:S5–6, 2003 Hot tub folliculitis HIV – primary infection; morbilliform eruption Am J Clin Dermatol 4:561–572, 2003; pruritic popular eruption of HIV disease BJD 170832–839, 2014 HIV-associated follicular syndrome – disseminated follicular spicules BJD 179;774–775, 2018 Human herpesvirus 6 – roseola infantum JAAD 58:308–316, 2008; exanthem after bone marrow transplant Bone Marrow Transplant 28:77–81, 2001; Human herpesvirus 7 – macular exanthem Human herpesvirus 8 – relapsing inflammatory syndrome; fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, exanthem of face, hands, wrists, and elbows NEJM 353:156–163, 2005 Izumi fever Insect bites, including avian mite bites (Dermanyssus gallinae) – diffuse morbilliform rash The Clinical Management of Itching; Parthenon; p. 62, 2000 Katayama fever (acute schistosomiasis) – red papular exanthem, fever, cough, urticarial eruption, fatigue, pulmonary nodules NEJM 374:469, 2016 Lassa fever (arenavirus) – morbilliform or petechial rash with conjunctivitis J Infect Dis 155:445–455, 1985 Legionellosis – Pontiac fever; morbilliform rashes, pretibial erythema Medicine 59:188–205, 1980 Leishmaniasis – disseminated leishmaniasis JAAD 50:461–465, 2004; post-kala azar dermal leishmaniasis – morbilliform eruption BJD 157:1032–1036, 2007; papules of cheeks, chin, ears, extensor

Exanthem forearms, buttocks, lower legs; in India, hypopigmented macules; nodules develop after years; tongue, palate, genitalia BJD 160:311– 318, 2009; JAAD 34:257–272, 1996; E Afr Med J 63:365–371, 1986 Leprosy Clin Inf Dis 52:1342, 1388–1389, 2011; Clin Inf Dis 35:1388–1389, 2002 Leptospirosis – headache, myalgia, pharyngitis, morbilliform eruption, scleral injection J Clin Inf Dis 21:1–8, 1995; truncal red morbilliform, urticarial, pretibial, purpuric desquamative exanthema; exposure to fresh water JAAD 58:308–316, 2008; pretibial fever or canicola fever – blotchy erythema of legs; non-pruritic transient macular exanthema of face and trunk (rare) Listeriosis, congenital – grey-white papules or pustules with red margins; predilection for the back J Natl Med Assoc 57:290–296, 1965; purpura, morbilliform rashes J Cutan Pathol 18:474–476, 1991; Am J Dis Child 131:405–408, 1977 Lyme disease – morbilliform eruption NEJM 321:586–596, 1989; AD 120:1017–1021, 1984 Lymphogranuloma venereum – exanthems Malaria Marburg virus disease (Filovirus- maculopapular-vesicular S Afr Med J 60:751–753, 1981 Mayaro virus – arbovirus; fever, headache, myalgia, arthralgia; exanthema of trunk and extremities; Brazil and Trinidad JAAD 58:308–316, 2008 Measles (rubeola) diarrhea, headache, chills, myalgias, nausea and vomiting, red eyes, confluent exanthem spreading craniocaudally, enanthem, fever and rash; Koplik’s spots Clin Inf Dis 62:1021,1049, 2016; NEJM 372:2217, 2015; NEJM 372:2218– 2223, 2015; JAMA 311:345–346, 2014; JAAD 58:308–316, 2008; NEJM 355:440–443, 2006; atypical measles – exanthem, pancytopenia, abnormal liver function tests NEJM 371:358–366, 2014 Mediterranean spotted fever – Rickettsia conorii; morbilliform exanthem, spares the face, involves the palms and soles; petechial conjunctival lesions Ann NY Acad Sci 1166:167–171, 2009; Int J Med Sci 6:126–127, 2009; petechiae JAAD 49:363–392, 2003 Melioidosis (Burkholderia pseudomallei) – endemic in SouthEast Asia, skin and soft tissue infection common Int J Dermatol 58:221– 227, 2019 Meningococcemia – early may show discrete pink macules or papules or transient morbilliform or urticarial eruptions Pediatrics 60:104–106, 1977 Mite bites Molluscum contagiosum, generalized in hyper-IgE syndrome AD 142:775–780, 2006 Monkeypox – exanthem indistinguishable from smallpox (papulovesiculopustular) except for adenopathy NEJM 355:962–963, 2006; J Infect Dis 156:293–298, 1987; cervical, maxillary, and inguinal adenopathy; headache, fatigue; rash begins on face and moves downward; begins as macular eruption then papular, vesicular, pustular Clin Inf Dis 58:260–267, 2014 Murine typhus – R. typhi and ELB agent – blanching macular or morbilliform rash MMWR 52:1224–1226, 2003; J Clin Inf Dis 21:991, 1995 Mycobacterium tuberculosis – lichen scrofulosorum Ped Derm 17:373–376, 2000; AD 124:1421–1426, 1988; Clin Exp Dermatol 1:391–394, 1976 Mycoplasma pneumoniae – exanthem J Pediatr 87:369–373, 1975; varicella-like rash Am J Dis Child 128:254–256, 1974 North American blastomycosis – in AIDS

341

Onchocerciasis – acute papular onchodermatitis – non-specific papular rash BJD 121:187–198, 1989 O’Nyong-Nyong fever – fever, arthritis, lymphadenopathy; exanthem of face, trunk, extremities, especially the neck, back, inner thighs, and arms JAAD 58:308–316, 2008; Orf – generalized bullous orf Int J Derm 19:340–341, 1980; orf with reactive erythema multiforme Clin Inf Dis 56:1613,1675–1676, 2013 Papular urticaria Human Parechovirus type 3 infection – generalized morbilliform eruption with bright red feet Ped Derm 31:258–259, 2014 Parvovirus B19 infection – erythema infectiosum; morbilliform J Clin Inf Dis 21:1424–1430, 1995; skin colored papules of upper arms, anterior thighs; papular dermatitic eruption of thighs and forearms progressing to morbilliform eruption Hum Pathol 31:488–497, 2000; petechial exanthema in male bathing trunk area Ped Derm 22:430–433, 2005; mimicking measles and echovirus 9; generalized petechial exanthem Pediatrics 125:e787, 2010 Pediculosis – head lice – pediculid JAAD 50:1–12, 2004; generalized pruritic eruption NEJM 234:665–666, 1946; pruritic papules of nape of neck; pediculosis corporis (body lice) – excoriated papules Adv Parasitol 36:271–342, 1995 Peloderma strongyloides (nematode larvae) – exanthem of papules and pustules JAAD 51:S109–112, 2004 Penicillium marneffei – generalized papular eruption Lancet 344:110–113, 1994; Mycoses 34:245–249, 1991 Picornavirus Skin and Allergy News 30:38,1999 Pityrosporum folliculitis JAAD 52:528, 2005 Plague (Yersinia pestis) – macular, red, petechial or purpuric eruption (black death) West J Med 142:641–646, 1985 Pseudomonas – swimming pool or hot tub folliculitis; macules, papules, pustules, urticarial lesions JAMA 239:2362–2364, 1978; JAMA 235:2205–2206, 1976 Psittacosis – morbilliform eruption Br Med J 289:510–511, 1984; rose spots AD 120:1227–1229, 1984; erythema nodosum J Hyg 92:9–19, 1984; erythema multiforme Br Med J 2:1469–1470, 1965; disseminated intravascular coagulation AD 120:1227–1229, 1984 Q fever – Coxiella burnetii; red macules, morbilliform, papular, urticarial, and purpuric eruptions JAAD 49:363–392, 2003; Pediatr Inf Dis J 19:358, 2000 Rat bite fever (Streptobacillus moniliformis (pleomorphic facultative anaerobic bacillus) or Spirillum minor (Soduku)) – macular, papulopustular, petechial, or morbilliform widespread exanthem; palmoplantar rash; arthralgia, septic arthritis and chronic arthritis; Haverhill fever (raw milk) – papules, crusted papules, vesicles, pustules; chronic abscesses NEJM 381:1762, 2019; JAMA 321:1930–1931, 2019; Clin Inf Dis 60:1388, 1436–1437, 2015; AD 148:1411–1416, 2012; MMWR 53:1198–1202, 2005; Cleveland Clin Q 52(2):203–205, 1985; Pediatr Clin N Am 26:377–411, 1979 Relapsing fever (tick-borne relapsing fever) – Ornithodoros soft ticks transmitting Borrelia hermsii, B.turicata, or B. parkeri; 1–2cm rose-­colored macules, papules, petechiae, purpura, facial flushing; arthralgias, iritis, myalgia; found in cabins of coniferous forest of western United States or caves of southwest US JAAD 49:363–392, 2003; diffuse macular rash Reovirus Respiratory syncytial virus – fine macular eruption J Pediatr 65:368–370, 1964 Rickettsia parkeri rickettsiosis – Southeastern United States; Gulf coast tick (Amblomma maculatum); eschar with surrounding

342

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

petechiae, fever, lethargy, fatigue, headache, myalgia, arthralgia, morbilliform or vesiculopapular or papulopustular rash of trunk and extremities, palms and soles, and occasionally the face 0.5 to 4 days after fever; some lesions with small vesicle or pustule; morbilliform eruptions, discrete round macules and papules AD 146:641–648, 2010; Clin Inf Dis 47:1188–1196, 2008 Rickettsial pox – sparse papulovesicular exanthem (Kew Gardens spotted fever) JAAD 47:766–769, 2002; NY Med 2:27–28, 1946 Rocky Mountain spotted fever (Rickettsia rickettsii) – initially blanching pink macules, or morbilliform eruption of wrists and ankles; soon spreads to face, trunk, and extremities; palms and soles involved; becomes purpuric with acral gangrene Cutis 70:165–168, 2002; JAAD 2:359–373, 1980 Rose spots  Brucellosis  Leptospirosis  Meningitis   Miliary tuberculosis  Psittacosis   Rat bite fever   Salmonella - typhoid fever Clin Inf Dis 48:615–616;683–684, 2009; AD 105:252–253, 1972; Lancet 1:1211–1213, 1975; NEJM 340:869–876, 1999  Shigellosis  Trichinosis Rotavirus Roseola infantum (exanthema subitum) (human herpesvirus 6) (possibly human herpes virus 7 NEJM 352:768–776, 2005; BJD 132:614–616, 1995; Arch Dis Childhood 72:518–519, 1995; ) Ped Inf Dis J 13:1010, 1994; Am J Dis Child 119:152–154, 1970; – rosepink macules start on neck and trunk, then spread to face and extremities after the fever breaks; rarely vesicular; Ross river disease – fatigue, arthralgia, arthritis, morbilliform eruption of trunk, palms and soles, face, and scalp JAAD 58:308– 316, 2008 Rotavirus exanthem – pink-red 2–3 mm macules or papules on the trunk on days 3–6 of the illness Skin and Allergy News 30:38,1999; AD 121:253–254, 1985 Rubella – confluent macular exanthem with craniocaudal dissemination; Forscheimer spots NEJM 369:558, 2013; JAAD 58:308–316, 2008 Scabies, including crusted (Norwegian) scabies Scarlet fever –Streptococcus pyogenes; scarlatiniform (sandpaper) rash with flexural accentuation, perioral pallor; erythema marginatum JAAD 39:383–398, 1998 Schistosomiasis – schistosomal dermatitis – identical to swimmer’s itch Dermatol Clin 7:291–300, 1989 Scrub typhus (Orientia (Rickettsia) tsutsugamuchi) (larval stage of trombiculid mites (chiggers)) – headache and conjunctivitis; eschar with black crust; generalized macular or morbilliform rash Ped Derm 34:124–127, 2017; NEJM 373:2455, 2015; Clin Inf Dis 39:1329–1335, 2004; AD 139:1545–1552, 2003; Clin Inf Dis 18:624, 1994; JAAD 2:359–373, 1980 Seabather's eruption – larvae of Scyphomedusa, Linuche unguiculata (thimble jellyfish) JAAD 44:624–628, 2001; Linuche unguiculata (larvae of thimble jellyfish); Edwardsia lineate (larvae of sea anemone) Cutis 77:151–152, 2006; AD 60:227–237, 1949 Seaweed dermatitis Shigellosis – rose spots Am J Dis Child 119:152–154, 1970

Sindbis virus– arbovirus; fever, fatigue, morbilliform rash and vesicles on palms and soles, arthralgia, arthritis; Europe, Asia, Africa, Australia JAAD 58:308–316, 2008; Tyring, p.399, 2002 Smallpox – morbilliform exanthem as initial cutaneous manifestation; macular and papular exanthema of face and extremities develop vesicles, pustules, and umbilicated crusts; hemorrhagic smallpox more severe JAAD 65:1213–1218, 2011; Cutis 71:319– 321, 2003 Smallpox vaccination – with erythema multiforme Clin Inf Dis 37:251–271, 2003; eczema vaccinatum Clin Inf Dis 37:251–271, 2003 Staphylococcal scalded skin syndrome Staphylococcal scarlet fever Streptococcal toxic shock syndrome – morbilliform or scarlatiniform exanthem; painful localized edema and erythema; progression to vesicles and bullae Strongyloides stercoralis – disseminated strongyloidiasis with morbilliform exanthem JAAD 49:S57–60, 2003 Swimmer's itch – schistosomes and trichobilharzia JAAD 61:733– 750, 2009 Swine flu exanthema – personal observation Syphilis, secondary JAAD 82:1–14, 2020; NEJM 380:1062–1071, 2019; NEJM 368:561, 2013; – congenital syphilis Ped Derm 23:121–123, 2006; morbilliform eruption of legs Clin Infect Dis 46:451–452,472–473, 2008; macular syphilid; morbilliform or papular J Clin Inf Dis 21:1361–1371, 1995; roseolar eruptions (roseola syphiliticum) Clin Dermatol 38:160–175, 2020; nodular secondary syphilis JAMA Derm 152:83–84, 2016 Tacaribe viruses – Argentinian, Bolivian, and Venezuelan hemorrhagic fevers – erythema of face, neck, and thorax with petechiae Lancet 338:1033–1036, 1991; JAMA 273:194–196, 1994 Tick-borne relapsing fever – Ornithodoros (soft tick); Borrelia genus; high fever in irregular pattern, chills, headache, myalgia, arthralgia, fatigue, macular rash at end of fever, conjunctival injection, hepatosplenomegaly, epistaxis, meningeal signs Cutis 82:38–46, 2008; Pediatr Drugs 7:163–176, 2005 Tick typhus (Boutonneuse fever, Kenya tick typhus, African and Indian tick typhus) (ixodid ticks) – small ulcer at site of tick bite (tache noire) – black necrotic center with red halo; pink morbilliform eruption of forearms, then generalizes, involving face, palms, and soles; may be hemorrhagic; recovery uneventful JAAD 2:359–373, 1980 Tinea versicolor – personal observation Togavirus – morbilliform eruption Togavirus – morbilliform, maculopapular-petechial (Sindbis BJD 135:320–323, 1996; BJD 80:67–74, 1968; chikungunya Trans R Soc Trop Med Hyg 49:28–32, 1955; and O’Nyong-Nyong fever Trans R Soc Med Hyg 55:361–373, 1961; bunyavirus fevers) with joint pains; Ross River virus – morbilliform eruption and polyarthritis in Australia and Fiji Med J Aust 159:159–162, 1993; Barmah Forest virus – similar to Ross River virus Med J Aust 152:463–466, 1990 Toxic shock syndrome, either streptococcal or staphylococcal – widespread macular erythema, scarlatiniform, and papulopustular eruptions; occasional vesicles and bullae; edema of hands and feet; mucosal erythema; second week morbilliform or urticarial eruption occurs with desquamation at 10–21 days; diffuse erythema Clin Inf Dis 32:1470–1479, 2001; Rook p.2079, 1998, Sixth Edition; JAAD 39:383–398, 1998; Rev Infect Dis 11(Suppl 1):S1–7, 1989; JAAD 8:343–347, 1983

Exanthem 343 Toxoplasmosis (Toxoplasma gondii) – maculopapular eruption AD 136:791–796, 2000; macular, morbilliform, purpuric exanthemata; scarlatiniform desquamation; congenital – necrotic papules, roseola-like, erythema multiforme-like JAAD 60:897–925, 2009 Trichinosis – periorbital edema, conjunctivitis; transient morbilliform eruption, splinter hemorrhages JAAD 73:929–944, 2015; Can J Public Health 88:52–56, 1997; Postgrad Med 97:137–139, 143–144, 1995; South Med J 81:1056–1058, 1988 Trench fever (Bartonella quintana) – red macules, 1cm or less; headache, dizziness, fever lasting 4–8 days, malaise, chills, conjunctivitis, myalgias, arthralgias, severe shin pain, lymphadenopathy, evanescent rash; “culture negative endocarditis” JAAD 82:551–569, 2020; Clinics in Dermatol 28:483–488, 2010 Trichosporon beigelii – disseminated purpuric papules in acute lymphocytic leukemia Mycoses 39:195–199, 1996; Medicine65:268–279:1986 Trypanosomiasis – African; edema of face, hands, feet with transient red macular, morbilliform, targetoid, petechial or urticarial dermatitis (trypanids); circinate, annular of trunk JAAD 60:897–925, 2009; AD 131:1178, 1995; American – cutaneous inoculation (inoculation chagoma); edema with exanthem Tularemia – Francisella tularensis (non-encapsulated gram-negative coccobacillus); transmitted in tick feces; skin, eye, respiratory, gastrointestinal portals of entry; ulceroglandular, oculoglandular, glandular types; typhoidal, pneumonic, oropharyngeal, and gastrointestinal types; toxemic stage heralds macular, generalized morbilliform eruption, vesicular, pustular, nodular or plaque-like secondary eruption JAAD 49:363–392, 2003; erythema multiformelike rash, crops of red nodules on extremities Cutis 54:279–286, 1994; Medicine 54:252–269, 1985; vesiculopapular lesions of trunk and extremities Photodermatology 2:122–123, 1985 Typhoid fever – rose spots Clin Inf Dis 48:615–616,683–684, 2009; JAAD 58:308–316, 2008 Unilateral laterothoracic exanthema (asymmetric periflexural exanthem of childhood) AD 135:799–803, 1999; in adults BJD 143:224–226, 2000; Acta DV 77:79–80, 1997; JAAD 37:484–485, 1997 Vaccinia – vaccinia roseola; transient papulovesiculopustular; generalized exanthem after inoculation Varicella – vesiculopustular; disseminated herpes zoster; reinfection varicella Clin Inf Dis 52:907–909, 2011; post–varicella granulomatous dermatitis Cutis 93:50–54, 2014; J Dtsch Dermatol Ges 2:770–772, 2004; Hautarzt 52:1111–1114, 2001; BJD 138:161–168, 1998; Am J Dermatopathol 16:588–592, 1994; J Cutan Pathol 19:557, 1992; Int J Dermatol 29:652–654, 1990 Vesicular stomatitis virus – vesicular Viral vasculitis - personal observation Virus-associated hemophagocytic syndrome – macular exanthem Cancer 44:993–1002, West Nile virus – Culex salinarius; punctate (1–2mm) red macular, papular, or morbilliform eruption of neck, trunk, arms, or legs in 20% of patients; exanthem of trunk and proximal extremities, sparing the face, palms and soles, and mucous membranes JAAD 58:308–316, 2008; JAAD 51:820–823, 2004; JAAD 49:979–1000, 2003; Ann Int Med 137:173–179, 2002; Ann DV 128:656–658, 2001;

myalgia, headache, retro-orbital pain, edema; palatal petechiae; microcephaly; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) JAAD 75:1–16, 2016; JAMA Derm 152:691–693, 2016; Clin Inf Dis 61:1445,1485–1486, 2015; NEJM 360:2536– 2543, 2009; micropapular eruption of face with conjunctival injection JAMA Derm 153:326–327, 2018

INFILTRATIVE DISEASES Congenital self-healing histiocytosis Ped Derm 17:364–368, 2000 Generalized eruptive histiocytosis JAAD 50:116–120, 2004; Ped Derm 17:364–368, 2000 Histiocytosis – S100-CD1a+ histiocytosis; indeterminate and dermal dendritic cells; exanthema with multiple papules AD 147:995–997, 2011; non-Langerhans cell histiocytosis – generalized eruptive – exanthem with recurrent crops of red-brown papules, including the face Acta DV 87:533–536, 2007; JAAD 50:116–120, 2004; Am J Dermatopathol 18:490–504, 1996; associated with acute myelogenous leukemia JAAD 50:116–120, 2004; indeterminate cell histiocytosis – firm red, yellow, brown papules; more on trunk than head and neck; S-100, CD1a, HAM 56, CD 68, MAC 387, lysozyme, alpha-1 anti-trypsin, HLA-DR, CD 11c, CD 14b, factor XIIIa positive; reported with acute myelogenous leukemia and low grade lymphoproliferative disorders JAAD 50:116–120, 2004 Indeterminate cell histiocytosis – widespread erythematous papulonodular eruption BJD 158:838–840, 2008; BJD 153:206–207, 2005; Cutis 59:27–31, 1997 Intralymphatic histiocytes – blanching violaceous exanthem BJD 177:325–326, 2017 Juvenile xanthogranuloma – reticulated maculopapular eruption AD 105:99–102, 1972 Langerhans cell histiocytosis – cutaneous findings include crops of red-brown or red-yellow papules, vesicopustules, erosions, scaling, and seborrheic dermatitis-like papules, petechiae, purpura, solitary nodules, bronze pigmentation, lipid infiltration of the eyes, white plaques of the oral mucosa, onycholysis, and onychodystrophy JAAD 78:1035–1044, 2018; JAAD 39:372–374, 1998; Curr Prob Derm VI Jan/Feb 1994; Clin Exp Derm 11:183– 187, 1986; JAAD 13:481–496, 1985; Letterer–Siwe disease JAAD 18:646–654, 1988; adult Letterer–Siwe disease JAAD 36:628– 629, 1997 Lichen myxedematosus – generalized lichenoid eruption Mastocytosis – urticaria pigmentosa Acta DV (Stockh) 42:433–439, 1962; telangiectasia macularis eruptiva perstans – telangiectasia, erythema, brown pigmentation Leuk Lymphoma 46:35–48, 2005; AD 124:429–434, 1988; JAAD 7:709–722, 1982; diffuse cutaneous mastocytosis J Investig Dermatol Symp Proc 6:143–147, 2001; BJD 144:682–695, 2001

INFLAMMATORY DISEASES

Lancet 358:261–264, 2001

Asymmetric periflexural exanthem of childhood – unilateral laterothoracic exanthema of childhood; scarlatiniform, morbilliform, dermatitic AD 138:1371–1376, 2002; Ped Derm 19:461–462, 2002; JAAD 34:979–984, 1996; Ped Derm 12:112–115, 1995; JAAD 29:799–800, 1993; JAAD 27:693–696, 1992

Yellow fever

Eosinophilic pustular folliculitis of AIDS

Yersiniosis

Erythema annulare centrifugum

Zika virus – fever, pinpoint red papules coalescing into morbilliform (macular and papular exanthem) eruption, arthralgia, conjunctivitis,

Erythema multiforme Medicine 68:133–140, 1989; JAAD 8:763– 765, 1983; chronic erythema multiforme – personal observation

344 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Eosinophilic fasciitis – personal observation Erythema toxicum neonatorum Kikuchi’s disease (histiocytic necrotizing lymphadenitis) (subacute necrotizing lymphadenitis) – morbilliform eruption, urticarial, and rubella-like exanthems; red papules of face, back, arms; red plaques; erythema and acneiform lesions of face; exanthem overlying involved lymph nodes; red or ulcerated pharynx; cervical adenopathy; associations with SLE, lymphoma, tuberculous adenitis, viral lymphadenitis, infectious mononucleosis, and drug eruptions AD 142:641–646, 2006; Ped Derm 18:403–405, 2001; JAAD 22:909–912, 1990; Am J Surg Pathol 14:872–876, 1990; rubella-like eruption, generalized erythema and papules BJD 146:167–168, 2002

spastic paralysis (TSP); Jamaica, Senegal, Brazil (endemic areas) JAAD 64:152–160, 2011; Lancet 336:1345–1347, 1990; Proc Natl Acad Sci USA 77:7415–7419, 1980; BJD 79:229–236, 1967; BJD 78:93–100, 1966 Kaposi’s sarcoma Keratoacanthomas – eruptive, Grzybowski-type – papular eruption of the face, scalp, neck, and upper back JAAD 37:478–480, 1997; JAAD 29:299, 1993; Skin and Allergy News 30:1,63, 1999

Lymphocytoma cutis, disseminated Acta DV (Stockh) 40:10–18, 1960

Leukemia cutis – acute or chronic myelogenous leukemia Ped Derm 36:658–663, 2019; JAAD 40:966–978, 1999; acute lymphocytic leukemia J Dermatol 26:216–219, 1999; acute monocytic leukemia – diffuse papulonodular eruption; congenital aleukemic leukemia cutis Ped Derm 21:458–461, 2004; HTLV-1 leukemia/ lymphoma; myeloid dendritic cell leukemia BJD 158:1129–1133, 2008

Miliaria, including miliaria rubra

Leukemid

Neutrophilic eccrine hidradenitis (maculopapular/purpuric) JAAD 23:111–1113, 1990

Lymphoma – cutaneous T-cell lymphoma (CTCL) epidermotropic CTCL BJD 172:819–821, 2015; blastic natural killer cell lymphoma BJD 148:507–515, 2003; nasal NK/T-cell lymphoma JAAD 46:451–456, 2002; angioimmunoblastic T cell lymphoma (angioimmunoblastic lymphadenopathy with dysproteinemia) – morbilliform eruption JAAD 65:855–862, 2011; NEJM 361:900–911, 2009; BJD 144:878–884, 2001; JAAD 36:290–295, 1997; JAAD 1:227–32, 1979; angiocentric T–cell lymphoma AD 132:1105–1110, 1996; adult T-cell leukemia (HTLV-1) (HTLV-1 leukemia/lymphoma) AD 134:439–444, 1998; JAAD 34:69–76, 1996; Hodgkin’s disease AD 116:1038–1040, 1980; Hodgkin’s disease; disseminated mantle cell lymphoma – petechial morbilliform eruption JAMA Derm 150:94–96, 2014; HTLV-1 leukemia lymphoma – personal observation

Rosai-Dorfman disease – disseminated red papules and nodules of extremities JAMA 310:199–200, 2013 Sarcoid Q J Med 28:109–124, 1959; juvenile sarcoid JAAD 48:S99–102, 2003 Stevens-Johnson syndrome BJD 174:1194–1227, 2016 Toxic epidermal necrolysis BJD 68:355–361, 1956

METABOLIC DISEASES Cholinergic urticaria AD 123:462–467, 1987 Idiopathic hypoparathyroidism AD 112:991–992, 1976 Maple syrup disease (treated) JAAD 28:289–292, 1993 Methylmalonic acidemia, cobalamin C type AD 133:1563–1566, 1997 Multiple nutritional deficiencies – personal observation Pruritic urticarial papules and plaques of pregnancy (PUPPP) JAAD 39:933–939, 1998; bullae of forearms with exanthem BJD 162:220– 222, 2010; post-partum PUPPP Cutis 95:344–347, 2015 Scurvy – purpuric exanthem

NEOPLASTIC DISEASES Angioimmunoblastic T-cell lymphoma – morbilliform eruption AD 136:881–886, 2000; JAAD 38:992–994, 1998; AD 130:1551–1556, 1994 Diffuse cutaneous reticulohistiocytosis Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome) – macular or papular exanthem; fever and rash; to be differentiated from Langerhans cell histiocytosis, leukemia cutis, myofibromatosis, extramedullary hematopoiesis J Dermatol 33:628–631, 2006; AD 138:1208–1212, 2002; J Pediatr 130:352–357, 1997; AD 128:193– 200, 1992 Human T-lymphotropic virus type 1-associated infective dermatitis – chronic relapsing dermatitis; severe red and exudative dermatitis with scaling and crusting of scalp, forehead, eyelids, paranasal area, neck, retroauricular, external ear, axillae, groin; chronic watery nasal discharge, crusting of anterior nares, blepharoconjunctivitis; generalized fine popular rash with lymph nodes; onset of rash at age 2 years; most common form of transmission is breast feeding; harbinger of development of adult T-cell lymphotropic leukemia and HTLV-1 associated myelopathy (HAM)/tropical

Lymphomatoid granulomatosis (angiocentric lymphoma) – morbilliform eruption Ped Derm 17:369–372, 2000 Lymphomatoid papulosis Int J STD AIDS 29:1120–1122, 2018 Malignant histiocytosis – diffuse papulonodular eruption Hum Pathol 15:368–377, 1984 Myelodysplastic syndrome – disseminated cutaneous granulomatous eruptions Clin Exp Dermatol 18:559–563, 1993 Porokeratosis, disseminated superficial – personal observation Porokeratosis palmaris plantaris et disseminata Post-transplant Epstein-Barr virus-associated lymphoproliferative disorder JAAD 51:778–780, 2004 Pseudo-cutaneous T-cell lymphoma in HIV disease Am J Med 91:300–309, 1991 Syringomas – generalized eruptive syringomas SKINmed 11:311– 312, 2013 Waldenstrom’s macroglobulinemia – papular eruptions AD 134:1127–1131, 1998; Waldenstrom’s macroglobulinemia with neoplastic cellular infiltrate – deck chair sign JAAD 52:S45–47, 2005

PARANEOPLASTIC Cutaneous myeloid dendritic cell dyscrasia – associated with myelodysplasia, acute or chronic myelocytic leukemia – papulonoduar generalized exanthema Ann Diagn Pathol 25:85–91, 2016 Generalized eruptive histiocytosis associated with acute myelogenous leukemia JAAD 49:S233–236, 2003 Paraneoplastic pemphigus – lichenoid dermatitis AD 136:652–656, 2000

Exanthem 345 Paraneoplastic vasculitis – leukocytoclastic vasculitis J Rheumatol 18:721–727, 1991; Medicine 67:220–230, 1988 Thymoma-associated multiorgan autoimmunity GVH-like disease – generalized papulosquamous exanthema JAAD 57:683–689, 2007; Eur J Gastroenterol 15:565–569, 2003; Clin Exp Dermatol 22:287– 290, 1997 Trichodysplasia spinulosa – red exanthem; filiform, folliculocentric spiny papules; polyoma virus Ped Derm 32:545–546, 2015; J Invest Dermatol Symp Proc 4:268–271, 1999; Hautarzt 46:841–846, 1995

Pityriasis rosea – personal observation Pityriasis lichenoides chronica The Clinical Management of Itching; Parthenon; p. 137, 2000; Pityriasis rosea JAAD 15:159–167, 1986 Pityriasis rubra pilaris Psoriasis – guttate, plaque-type Recalcitrant erythematous desquamating disorder Clin Infec Dis 18:942–945, 1994 Scleredema

PHOTODERMATOSES Actinic reticuloid – personal observation Chronic actinic dermatitis Photosensitivity of AIDS Polymorphic light eruption The Clinical Management of Itching; Parthenon; p. xvi, 2000

PRIMARY CUTANEOUS DISEASES Amicrobial pustulosis – associated with systemic autoimmune disorders; scalp, axillae, ears, thighs JAAD 57:523–526, 2007; Communication no.11. Journees Dermatologiques de Paris, March 1991. CARD 14-associated papulosquamous eruption – features of psoriasis, pityriasis rubra pilaris, atopic dermatitis JAAD 79:487– 494, 2018 Cholinergic urticarial – personal observation Darier's disease – personal observation Diaper dermatitis with rapid dissemination – expanding nummular dermatitis of trunk, and red scaly plaques of neck and axillae (“psoriasiform id”) BJD 78:289–296, 1966 Dowling-Degos disease, generalized JAAD 57:327–334, 2007 Episodic nontoxic erythema AD 132:1387–1388, 1996 Exanthematous elastolytic granuloma JAAD 19:564–565, 1988 Granuloma annulare – disseminated JAAD 75:457–465, 2016; JAAD 3:217–230, 1980; disseminated in AIDS JAAD 20:232–235, 1989; pustular generalized granuloma BJD 149:866–868, 2003 Granulomatous periorificial dermatitis – extrafacial and generalized periorificial dermatitis AD 138:1354–1358, 2002 Grover’s disease – personal observation Id reaction JAAD 55:923–925, 2006 Kawasaki’s disease – personal observation Kikuchi’s disease – red macules, malar erythema, oral ulcers, photosensitivity, conjunctival injection, lymphadenopathy, fever, arthralgia JAAD 59:130–136, 2008; morbilliform eruption Ped Derm 24:459–460, 2007 Lichen nitidus, generalized Ped Derm 26:109–111, 2009 Large plaque parapsoriasis Lichen planus Ped Derm 27:34–38, 2010 Mucha-Habermann disease (acute parapsoriasis) – BJD 86:215– 225, 1972; acute febrile ulceronecrotic Mucha-Habermann disease (acute parapsoriasis) – painful hemorrhagic ulcers Ped Derm 31:525–527, 2014; Ped Derm 22:360–365, 2005; BJD 152:794– 799, 2005; JAAD 49:1142–1148, 2003; BJD 147:1249–1253, 2002; J Rheumatol 16:387–389, 1989; AD 100:200–206, 1969; Ann DV 93:481–496, 1966 Papular urticaria – personal observation

Seborrheic dermatitis

SYNDROMES Angiokeratoma corporis diffusum Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; onset under 4 years of age; generalized micropapular rash of trunk and extremities infancy (ichthyosiform); translucent skin-colored papules (non-caseating granulomas) of trunk and extremities or dense lichenoid yellow to red-brown papules with grainy surface with anterior or panuveitis, synovitis, symmetric granulomatous polyarthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; exanthema resolves with pitted scars; camptodactyly (flexion contractures of PIP joints); no involvement of lung or hilar nodes; sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathies, interstitial lung disease, nephritis, arterial hypertension, pericarditis, pulmonary embolism, hepatic granulomas, chronic renal failure; activating mutations in NOD2 (nucleotidebinding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) Ped Derm 34:216–218, 2017; Ped Derm 27:69–73, 2010; AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996; J Pediatr 107:689–693, 1985 Cardio-facio-cutaneous syndrome – personal observation Chronic infantile neurological cutaneous articular syndrome (CINCA) (neonatal onset multisystem inflammatory disorder (NOMID)) Eur J Ped 156:624–626, 1997 Familial cold autoinflammatory syndrome (cold urticaria) – nonpruritic urticarial rash precipitated by cold; conjunctivitis, arthralgias of knees and ankles and arthritis; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin) BJD 178:335–349, 2018; AD 142:1591–1597, 2006; JAAD 54:319–321, 2006; BJD 150:1029–1031, 2004; JAMA 114:1067–1068, 1940 Familial dysautonomia (Riley-Day syndrome) (hereditary sensory and autonomic neuropathy type III) – blotchy erythema in infancy with 2–5cm red macules on trunk and extremities AD 89:190–195, 1964 Glucagonoma syndrome Hemophagocytic syndrome (hemophagocytic lymphohistiocytosis), reactive – reacts to B- or T-cell lymphoma or herpes simplex infection; transient generalized morbilliform exanthem; erythroderma, purpuric macules, lymphadenopathy, pancytopenias, increased ferritin, high triglycerides Blood Rev 28:135–142, 2014; Best Pract Res Clin Rheumatol 28:277–292, 2014; Eur Rev Med Pharmacol Sci 16:1414–1424, 2012; BJD 162:547–553, 2010; Crit Rev Oncol Hematol 50:157–174, 2004; familial hemophagocytic syndrome – morbilliform eruptions, purpuric macules, acral blanching red macules, erythroderma, fever, and edema JAAD 56:302–316, 2007; AD 138:1208–1212, 2002; histiophagocytic syndrome – generalized macular rash Cancer 44:993–1002, 1979; morbilliform rash Am J Med 93:177–180, 1992; parvovirus

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B19-induced histiophagocytic syndrome – bilateral facial rash and generalized morbilliform eruption J Infect Dis 58:149–151, 2005 Hereditary lactate dehydrogenase M-subunit deficiency – annually recurring acroerythema JAAD 27:262–263, 1992 Hypereosinophilic syndrome – widespread facial and truncal morbilliform eruption JAAD 49:918–921, 2003 Hyper IgD syndrome – periodic fever, morbilliform eruption, red macules or papules, urticaria, annular erythema, red nodules, oral aphthae, arthralgias, abdominal pain, lymphadenopathy; combinations of fever, arthritis, and rash, annular erythema, and pustules; mevalonate kinase gene AD 136:1487–1494, 2000; Ann DV 123:314–321, 1996; AD 130:59–65, 1994 IgG4-related disease – cutaneous plasmacytosis (papulonodules); pseudolymphoma; angiolymphoid hyperplasia with eosinophilia; Mikulicz’s disease; psoriasiform dermatitis; morbilliform eruption; hypergammaglobulinemic purpura; urticarial vasculitis; ischemic digits; Raynaud’s disease and digital gangrene BJD 171:929,959– 967, 2014 Incontinentia pigmenti Kawasaki's disease – macular, morbilliform, urticarial, scarlatiniform, erythema multiforme-like, micropustular, erythema marginatum-like exanthems, erythrodermic; non-suppurative conjunctivitis, strawberry tongue; cheilitis; edematous hands with lamellar desquamation; myocarditis and coronary artery thrombosis and aneurysms; arthralgia, arthritis JAAD 69:501–510, 2013; JAAD 39:383–398, 1998; Jpn J Allergol 16:178–222, 1967 Kindler's syndrome Mitochondrial DNA syndrome JAAD 39:819–823, 1998 Muckle-Wells syndrome – autosomal dominant; macular erythema (evanescent red macules), urticaria (cold air urticaria), deafness, extremity pain, arthralgias of knees and ankles with arthritis; nephropathy, AA amyloidosis with neuropathy; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin) AD 142:1591–1597, 2006; BJD 151:99–104, 2004; JAAD 39:290–291, 1998; Q J Med 31:235–248, 1962 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – urticarial lesions, chronic meningitis, arthralgias of knees and ankles with deforming arthropathy with epiphyseal bone formation, deafness, hepatosplenomegaly, uveitis, vitreitis, papilledema, corneal stromal keratopathy; mental retardation; fever and rash more severe in evening; mutation in NALP3 (CIAS 1) which encodes cryopyrin AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319–321, 2006; Ped Derm 22:222– 226, 2005

Sweet's syndrome Systemic-onset juvenile idiopathic arthritis (SOJIA syndrome) – spiking fevers, daily evanescent morbilliform eruption, polyarticular arthritis JAAD 68:834–853, 2013 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) – morbilliform exanthema; Still’s disease-like eruption with erythematous patches, tender red plaques, fever, annular, generalized serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, centrifugal migratory red patch overlying myalgia, red cheeks; lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia, abdominal pain, headache; Irish and Scottish predominance; mutation in tumor necrosis factor receptor superfamily 1A (TNFRSF1A gene) – gene encoding 55kDa TNF receptor BJD 161:968–970, 2009; Medicine 81:349–368, 2002; Netherlands Journal of Medicine 59:118–125, 2001; AD 136:1487–1494, 2000; Mayo Clin Proc 62:1095–1100, 1987

TOXINS Alcohol – acute alcohol consumption; dermatitis of legs, trunk, and perineal areas BJD 155:195–197, 2006 Arsenic – acute arsenic intoxication; initially morbilliform eruption with development of vesicles, pustules on red background; followed by generalized desquamation and palmoplantar lamellar desquamation BJD 149:757–762, 2003; BJD 141:1106–1109, 1999 Carbon monoxide poisoning – cherry red discoloration of skin; nails pink become dark blue-red; scalp edema and erythema Clin Dermatol 37:136–147, 2019 Ciguatera fish poisoning Eosinophilic myalgia syndrome (l-tryptophan-induced) – morbilliform eruption JAAD 25:54–58, 1991; faint macular red exanthema JAAD 23:1063–1069, 1990 Mercury – hypertensive, tachycardic, photophobic, irritable (resembles pheochromocytoma) miliaria-like eruption; morbilliform exanthem JAAD 43:81–90, 2000 Schnitzler’s syndrome – chronic urticaria with IgM gammopathy JAAD 57:361–364, 2007 Scombroid fish poisoning Wissler’s syndrome – diffuse erythema Acta Paediatr 49:90–95, 1960

Recalcitrant erythematous desquamating (RED) syndrome – diffuse macular erythema, ocular and mucosal erythema, strawberry tongue, delayed desquamation in the setting of AIDS JAAD 39:383–398, 1998

TRAUMA

Relapsing polychondritis – toxic erythema Medicine 55:193–216, 1976; morbilliform eruption Clin Exp Rheumatol 20:89–91, 2002

Sunburn

Reticulated erythematous mucinosis – personal observation Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – butterfly rash, facial dermatitis, exanthema, papules, annular, atypical targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAMA Derm 153:461–462, 2017; BJD 142:343–346, 2000; Clin Exp Dermatol 24:74–77, 1999; JAAD 21:374–377, 1989: AD 88:176– 180, 1963

Phototherapy of neonatal jaundice – macular red rash as bilirubin falls JAMA 208:1703, 1969

VASCULAR Angiolymphoid hyperplasia with eosinophilia – disseminated papules over face, trunk and extremities Cutis 72:323–326, 2003 Eosinophilic granulomatosis with polyangiitis – erythema multiforme-­like exanthems Autoimmun Rev 14:341–348, 2015; Dermatopathol 37:214–221, 2015; JAAD 37:199–203, 1997; JID 17:349–359, 1951; Am J Pathol 25:817, 1949

Exfoliation (Desquamation) Degos’ disease Seminars in Derm 14:99–105, 1995 Eruptive pseudoangiomatosis – sudden appearance of few to numerous bright red papules; transient dilatation of dermal capillaries; lasts 2–18 days in children, 1–3 months in adults J Eur Acad Dermatol Venereol 18:387–389, 2004; AD 140:757–758, 2004; JAAD 29:857–859, 1993; Pediatr 44:498–502, 1969 Generalized essential telangiectasia Granulomatosis with polyangiitis QJMed 208:435–460, 1983 Henoch-Schonlein purpura – personal observation Leukocytoclastic vasculitis, morbilliform – personal observation Pigmented purpuric eruption, generalized Polyarteritis nodosa Arch Dis Child 55:569–572, 1980; infantile polyarteritis nodosa – exanthem JAMA 217:1666–1670, 1971, J Pediatr 120:206–209, 1992 Telangiectasias secondary to liver disease

EXFOLIATION (DESQUAMATION)  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Fogo selvagem Graft vs. host disease – desquamation following acute exanthem Transpl Proc 44:1751–1753, 2012; AD 124:1849–1850, 1988 IgA pemphigus – red plaque with desquamation BJD 171:650–656, 2014 Pemphigus foliaceus – personal observation Pemphigus herpetiformis – red plaque with vesicles, circinate desquamation, erosions, urticarial lesions Ped Derm 34:342–346, 2017

347

Doxorubicin – pegylated liposomal doxorubicin resulting in eccrine squamous syringometaplasia; red plaque with desquamation AD 144:1402–1403, 2008 Drug reaction with eosinophilia and systemic symptoms (DRESS) – morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, facial edema, lymphadenopathy JAAD 68:693–705, 2013 Epidermal growth factor receptor inhibitors – desquamation of finger tips JAAD 56:460–465, 2007 Etretinate – personal observation Levofloxacin Curr Drug Safety July 8, 2019 Retinoids – topical or systemic Salicylic acid Membranous desquamation following morbilliform drug eruption Radiation recall – capecitabine, doxorubicin, taxanes, gemcitabine; erythema and desquamation; edema; vesicles and papules; ulceration and skin necrosis The Oncologist 15:1227–1237, 2010 Sirolimus Am J Transpl 14:221–225, 2014 Taxotere feet – personal observation Thiotepa – diffuse erythema, desquamation, and hyperpigmentation JAAD 58:575–578, 2008 Trimethoprim-sulfamethoxazole – localized exfoliation DICP 24:140–142, 1990

EXOGENOUS AGENTS Betel quid chewing – peeling of oral mucous membrane with underlying wrinkled appearance Cutis 71:307–311, 2003 Hypervitaminosis A – desquamation Irritant contact dermatitis Pustular reaction to rubber gloves

CONGENITAL LESIONS

Selenium excess – exfoliative dermatitis

Collodion baby Dysmature or small-for-dates neonates vernix caseosa – “crazed” with long transverse splits on the trunk which peels

INFECTIONS AND INFESTATIONS

Ectodermal dysplasias at birth

Bullous impetigo – resolving

Lamellar exfoliation of the newborn Ophthalmologica 152:68–73, 1966

Chikungunya fever – desquamation over face Indian J Dermatol 56:290–294, 2011

Palmoplantar desquamation – normal finding Ped Derm 23:61–63, 2006

Coccidioidomycosis – palmar desquamation following acute exanthem JAAD 55:929–942, 2006

Physiologic scaling of the newborn – appears around ankles on day 1, confined to hands and feet JAAD 23:77–81, 1990

Colorado tick fever – Orbivirus; macules, papules, morbilliform eruption; branny desquamation JAAD 49:363–392, 2003

Postmaturity syndrome in newborns – desquamation J Maternal Fetal Neonatal Med Oct 23, 2019

Corynebacterium haemolyticum – pharyngitis, scarlatiniform rash Ann Int Med 105:867–872, 1986

Toxic erythema of the newborn

Ebola virus hemorrhagic fever (Filovirus) – exanthem which becomes purpuric with desquamation of palms and soles JAAD 65:1213–1218, 2011; MMWR 44, No.19, 382, 1995

Transient neonatal pustular melanosis Vernix caseosa – white, greasy film present at birth, may be accentuated in flexures (groin)

DRUGS Azathioprine Dermatology 194:175–176, 1997

Leprosy – erythema nodosum leprosum; acute lesions erupt then desquamate; onychomadesis (shedding of nail); erythroderma An Bras Dermatology 94:89–92, 2019 Lyme disease – centrifugal desquamation with collarette of scale JAAD 49:363–392, 2003

Benzoyl peroxide

Marburg virus (Filovirus) – exanthem which becomes purpuric with desquamation of palms and soles JAAD 65:1213–1218, 2011

Diltiazem – palmar desquamation BMJ Case Rep Sept 26, 2013

Measles

348 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Recurrent toxin-mediated perineal erythema – associated with pharyngitis due to Staphylococcus aureus or Streptococcus pyogenes AD 144:2390243, 2008; AD 132:57060, 1996

Pellagra

Rocky Mountain spotted fever

Renal failure BMJ 4(833):179, 1972

Scabies – Norwegian scabies in HTLV-1 disease; personal observation

Vitamin A intoxication Clin Toxicol 56:146–148, 2018

Scarlet fever JAAD 39:383–398, 1998

Propionic aciduria – desquamating eruptions Ped Derm 16:95–102, 1999

Zinc deficiency – in cystic fibrosis, alcoholism – personal observation

Staphylococcal scalded skin syndrome JAAD 39:383–398, 1998 Syphilis, congenital – palmar and generalized desquamation following pemphigus syphiliticum Ped Derm 35:e110–113, 2018; secondary syphilis mimicking tinea imbricata JAAD 61:165–167, 2009 Tinea imbricata Tinea manuum Acta DV (Stockh) 36:272–278, 1956 Tinea versicolor Semin Dermatol 4:173–184, 1985

NEOPLASTIC DISEASES HTLV-1 lymphoma – palmar exfoliation BJD 128:483–492, 1993; Am J Med 84:919–928, 1988

PARANEOPLASTIC DISEASES

Toxic shock syndrome, streptococcal Curr Prob in Dermatol 14:183–220, 2002; JAAD 39:383–398, 1998; AD 131:73–77, 1995; staphylococcal – widespread macular erythema, scarlatiniform, and papulopustular eruptions; occasional vesicles and bullae; edema of hands and feet; mucosal erythema; second week morbilliform or urticarial eruption occurs with desquamation at 10–21 days Curr Prob in Dermatol 14:183–220, 2002; Clin Inf Dis 32:1470–1479, 2001; JAAD 39:383–398, 1998; Rev Infect Dis 11(Suppl 1):S1–7, 1989; JAAD 8:343–347, 1983; Group B streptococcal toxic shock syndrome AD 140:163–165, 2004

Acrokeratosis paraneoplastica – hand edema, desquamation of hands; hyperkeratotic and lichenified plaques of hands; vesicles and bullae of hands JAMA Derm 151:677–678, 2015

Toxoplasmosis

Annular epidermolytic hyperkeratosis – congenital peeling JAAD 27:348–355, 1992

Trichosporosis, neonatal – generalized peeling Viral exanthem, resolving Zika virus – palmar desquamation; microcephaly at birth; fever, morbilliform rash, arthritis, arthralgias, conjunctivitis JAAD 75:1–16, 2016 Zygomycosis, neonatal – generalized peeling with development of necrotic ulcers

INFLAMMATORY DISEASES Stevens-Johnson syndrome Toxin-mediated erythema Toxic epidermal necrolysis

METABOLIC DISEASES Kwashiorkor – edema and “flaky paint” desquamation; varnished hyperkeratosis, dry brittle hair, alternate normal/red bands of hair color Clin in Dermatol 38:79–85, 2020; JAMA Derm 150:910–911, 2014; JAMA Derm 150:85–86, 2014; JAAD 52:S69–72, 2005; Cutis 67:321–327, 2001 ; Ped Derm 16:95–102, 1999; AD 134:107–108, 1998 Methylmalonic acidemia – deficiency of methylmalonyl coenzyme A mutase or its cofactors adenosylcobalamin (vitamin B12) and methylcobalamin; affects metabolism of four amino acids (valine isoleucine, threonine, methionine); these patients fed low protein diets limited in branched chain amino acids Ped Derm 24:455–456, 2007; Dermatol Pediatr Lat 1:46–48, 2003; Ped Derm 16:95–102, 1999; AD 133:1563–1566, 1997; J Pediatr 124:416–420, 1994; BJD 131:93–98, 1994 Multiple nutritional deficiencies – personal observation Peeling skin syndrome with aminoaciduria Ped Derm 22:314–316, 2005

PRIMARY CUTANEOUS DISEASES Acropustulosis of infancy – personal observation Annular bullous congenital ichthyosiform erythroderma – annular desquamation; novel KRT10 mutation BJD 157:602–604, 2007

Autosomal recessive exfoliative ichthyosis – congenital erythroderma, diffuse hyperkeratosis, palmoplantar keratoderma, palmoplantar peeling, hyperhidrosis, erosions; mutation in cysteine protease inhibitor A (cystatin A) BJD 172:1628–1632, 2015 Blype = desquamation JAAD 56:857, 2007 Epidermolysis bullosa simplex superficialis – EB with subcorneal skin cleavage mimicking peeling skin syndrome AD 125:633–638, 1989 Epidermolytic hyperkeratosis – desquamation of newborn Semin Dermatol 12:202–209, 1993 Episodic nontoxic erythema (episodic toxin-mediated erythema) – swelling of the extremities followed by generalized tender sunburnlike erythema, followed by exfoliation AD 132:1387–1388, 1996 Erythrokeratoderma hiemalis (erythrokeratolysis hiemalis (Oudtshoorn disease)) (keratolytic winter erythema) – palmoplantar erythema, cyclical and centrifugal peeling of affected sites, targetoid lesions of the hands and feet; annular serpiginous lesions of lower legs, knees, thighs, upper arms, shoulders – seen in South African whites; precipitated by cold weather or fever Curr Prob Derm 14:71–116, 2002; S Afr Med J 52:871–874, 1977; BJD 98:491–495, 1978 Erythrokeratoderma variabilis – palmoplantar scaling BJD 143:1133–1139, 2000 Exfoliative erythrodermas Ichthyosis bullosa of Siemens (superficial epidermolytic ichthyosis) – autosomal dominant; mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray rippled hyperkeratosis of extremities, lower trunk, flexures; peeling; hypertrichosis; circumscribed patchy scaling (mauserung); palmoplantar blistering with hyperhidrosis Ped Derm 30:469–472, 2013; Ped Derm 27:653–654, 2010; Curr Prob Derm 14:71–116, 2002; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986; BJD 140:689–695, 1999; Arch Derm Res 282:1–5, 1990; Arch Derm

Exfoliation (Desquamation)

349

Syph 175:590–608, 1937; knees, dorsal hands, and ankles; palms and soles spared

166:894–896, 2012; Clin Genet 80:50–58, 2011; J Cutan Pathol 36:553–559, 2009

Ichthyosis exfoliativa, autosomal dominant BJD 124:191–194, 1991

Chondrodysplasia punctata – Conradi's disease

Ichthyosis exfoliativa – autosomal recessive; peeling of neonate; resembles ichthyosis bullosa of Siemens in adult life BJD 149:174– 180, 2003

Congenital insensitivity to pain – autosomal recessive; xerosis with desquamation; anhidrosis with palmoplantar keratoderma; unilateral plantar ulcer; mutation in NTRK1 Ped Derm 30:754–756, 2013

Ichthyosis vulgaris

Ectodermal dysplasia-skin fragility syndrome – autosomal recessive; plakophillin gene mutation (PKP1) – generalized erythema and peeling at birth; widespread skin fragility, alopecia of scalp and eyebrows, focal palmoplantar keratoderma with painful fissures, hypohidrosis; skin peeling; perioral fissuring and cheilitis; perianal erythema and erosions, follicular hyperkeratosis JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004

Juvenile plantar dermatosis Clin Exp Dermatol 11:529–534, 1986; Semin Dermatol 1:67–75, 1982; Clin Exp Dermatol 1:253–260, 1976 Keratolysis exfoliativa (acquired peeling of the palms) – recurrent Dermatol Online J Dec 16, 2015; BJD 167:1076–1084, 2012; Trans St John’s Hosp Dermatol Soc 53:165–167, 1967; Keratolytic winter erythema (Oudtshoorn disease) – autosomal dominant; seasonal desquamation of the palms and soles AD 142:1073–1074, 2006 Lamellar ichthyosis variants Leiner’s disease Lethal acantholytic epidermolysis bullosa – autosomal recessive; mutation in desmoplakin (DSP) – cutaneous and mucosal epidermal shedding, skin fragility, total alopecia, anonychia JID 130:2680–2683, 2010; BJD 162:138801394, 2010; Dermatol Clin 28:131–135, 2010; mutation in JUP gene Hum Med Genet 20:1811–1819, 2011 Mucosal shedding syndrome - personal observation Miliaria crystallina Cutis 47:103–106, 1991 Necrolytic acral erythema – acral velvety hyperpigmented and hyperkeratotic plaques of distal dorsal feet; red palms with desquamation, erythroderma with flaccid bullae, edema and desquamation of face, onychodystrophy and onychomadesis; hepatitis C Cutis 84:301–304, 2009 Progressive symmetric erythrokeratoderma – personal observation Pustular psoriasis of von Zumbusch – personal observation X-linked ichthyosis

SYNDROMES Acral peeling skin syndrome – autosomal recessive; thin, flaccid distal bullae with desquamation in infancy; older children get skin peeling; mutation in transglutaminase 5 (TGM5) or cystatin A (CSTA) BJD 172:276–278, 2015; BJD 171:1206–1210, 2014; JAMA Derm 150:647–648, 2014; BJD 169:1322–1325, 2013; Ped Derm 29:258–263, 2012; Ped Derm 26:328–330, 2009; JAAD 43:1112– 1119, 2000; AD 133:535–536, 1997; JAAD 7:606–613, 1982; AD 3:202, 1921; type B – mutation in corneodesmosin BJD 166:36–45, 2012 Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, superficial blisters and desquamation of hands and feet; lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears hooked nose, sparse thin blond hair, frontal alopecia, hypohidrosis, lacrimal duct atresia, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene (encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes BJD 172:276–278, 2015; Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993 Carvajal-like syndrome – blisters, woolly hair, palmoplantar kertoderma, cardiac abnormalities; heterozygotes of DSP BJD

Glucagonoma syndrome Ichthyosis prematurity syndrome (“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; premature erythrodermic infant with caseous vernix-like desquamation; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine scaling of scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin (thick vernix caseosa-like covering) (hyperkeratotic scalp) neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4 (FATP4); mutation in SLC 27A4 (AMF-binding domain of FATP4) JAMA Derm 152:1055–1058, 2016; JAAD 66:606–616, 2012; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008; hyperkeratotic cobblestoning of back of neck, flexural hyperpigmented follicular hyperkeratosis, intertriginous hyperpigmentation and hyperkeratotic plaques in the adult JAMA Derm 152:1055–1058, 2016 Kawasaki's disease – recurrent skin peeling Arch Dis Child 83:353–355, 2000; membranous desquamation of hands and feet accentuated in periungual areas JAAD 69:501–510, 2013; JAAD 39:383–398, 1998; perianal erythema and desquamation AD 124:1805–1810, 1988 Netherton’s syndrome – ichthyosis linearis circumflexa Peeling skin syndrome (erythrokeratolysis, familial peeling skin syndrome, keratolysis exfoliativa congenita, deciduous skin) – autosomal recessive; type A – non-inflammatory; type B – inflammatory; generalized superficial peeling at birth or early childhood; reported with easily plucked hair, shedding of nails, stunted growth with hypogonadism, anosmia; corneodesmosin (CDSN) mutation Ped Derm 32:244–247, 2015; JAMA Derm 151:225–226, 2015; Ped Derm 23:488–492, 2006; Int J Dermatol 38:208–210, 1999; JAAD 30:135–136, 1994; BJD 116:117–125, 1987; AD 122:71–75, 1986; AD 9:487–498, 1924; Arch Dermatol Syphilol 3:202, 1921; familial peeling skin syndrome with eosinophilia Arch Pathol Lab Med 120:662–665, 1996; type A (non-inflammatory); type B (inflammatory) – autosomal recessive; erythroderma, congenital onset, pruritus, infections Ped Derm 19:382–387, 2002; peeling skin syndrome, fissured cheilitis, blistering of palms and soles, and desmosomal abnormalities JAAD 34:379–385, 1996 Recalcitrant erythematous desquamating (RED) syndrome - diffuse macular erythema, ocular and mucosal erythema, strawberry tongue, delayed desquamation in the setting of AIDS JAAD 39:383–398, 1998 Rubinstein-Taybi syndrome – novel mutation in bromodomain of CREBBP gene Clin Exp Derm 44:e205–208, 2019 SAM syndrome spectrum – palmoplantar keratoderma; multiple allergies, growth retardation, high IgE; DSG1

350 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 X-linked hypohidrotic ectodermal dysplasia – neonatal scaling mimicking physiologic scaling of the newborn J Pediatr 114:600– 602, 1989

TOXINS Acrodynia (pink disease) – mercury poisoning; AD 124:107–109, 1988; desquamation of fingertips and palms Ped Derm 21:254–259, 2004; mercurochrome Clin Toxicol 13:79–96, 1978; profuse sweating; red edematous hands and feet, hypertension, severe periumbilical pain, irritability Ped Derm 29:199–201, 2012; Pediatr Nephrol 22:903–906, 2009; Arch Dis Child 62:293–295, 1987; Lancet 29:829–830, 1948; Arch Dermatol Syphilol 26:215–237, 1932; Rev Med Fr 3:51–74, 1830 Arsenic – acute arsenic intoxication; initially morbilliform eruption with development of vesicles, pustules on red background; followed by generalized desquamation and palmoplantar lamellar desquamation BJD 149:757–762, 2003; BJD 141:1106–1109, 1999; acute arsenic beer poisoning – garlic odor of skin; yellow-brown pigment, sore tongue, photophobia, alopecia, shedding nails BJD 165:209– 210, 2011

TRAUMA Burns – thermal, sunburn Liver transplant – lamellar desquamation; personal observation

VASCULAR DISEASES Erythrocyanosis – may have ulceration, erythema, keratosis pilaris, desquamation, nodular lesions, edema, and fibrosis Lymphedema – post-lymphedema lamellar desquamation; personal observation Polyarteritis nodosa, infantile – desquamation of the hands and feet J Pediatr 120:206–209, 1992; JAMA 217:1666–1670, 1971

Staphylococcal scalded skin syndrome Intern Med J 35Suppl2:S106–119, 2005 Streptococcus pyogenes – streptococcal perianal dermatitis; digital desquamation Clin Pediatr 39:237–239, 2000 Toxic shock syndrome Zinc deficiency

EYELID LESIONS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Airborne allergic contact dermatitis JAAD 15:1–10, 1986 Allergic contact dermatitis – systemic contact dermatitis to foods – flexural dermatitis, eyelid, genital, dyshidrosis Cutis 104:337–340, 2019; medications, cosmetics, fragrances, occupational – eyelid edema JAAD 48:617–619, 2003; Contact Dermatitis 42:291–293, 2000; JAAD 41:435–442, 1999; sensitization to cobalt in a dental prosthesis – lid edema BJD 136:971–972, 1997; epoxy resins Contact Dermatitis 19:279–280, 1988; plant dermatitis; woods; nail polish Contact Dermatitis 34:140–141, 1996; acrylic nails; neomycin, idoxuridine, other topical medications Surv Ophthalmol 24:57–88, 1989; airborne allergen blepharitis Clin Therap 17:800– 810, 1995; nickel in eye pencil The Clinical Management of Itching; Parthenon; p. 117, 2000; eyelash curler Contact Dermatitis 25:77, 1991; contact lens cleaner Contact Dermatitis 24:232–233. 1991; protein contact dermatitis JAAD 47:755–765, 2002; airborne gold allergic contact dermatitis – eyelid dermatitis 21:284–287, 2010; eyelid dermatitis as manifestations of systemic contact dermatitis to cinnamon Dermatitis 26:188–189, 2015 Angioedema JAAD 25:155–161, 1991; Dermatol Clin 3:85–95, 1985 Anti-laminin 332 mucous membrane pemphigoid – conjunctivitis with symblepharon; desquamative gingivitis BJD 169:100–105, 2013 Autoimmune progesterone dermatitis – fixed drug-like lesions

LAMELLAR DESQUAMATION OF THE FINGERTIPS Blistering distal dactylitis Bullous impetigo Burns Contact dermatitis Dyshidrosis Dermatology 198:265–269, 1999 Epidermolysis bullosa Graft vs. host disease Hypervitaminosis A Am J Clin Nutr 52:183–202, 1990 Kawasaki’s disease Keratolysis exfoliativa Leptospirosis – patchy palmar dysesthesia Am J Trop Med Hyg 74:127–131, 2006 Liver transplant Palmoplantar erythrodysesthesia Eur J Oncol Nurs 11:238–246, 2007 Pityriasis rubra pilaris – juvenile acute form Ped Derm 18:411–414, 2001 Recalcitrant erythematous desquamating disorder (RED disorder) Scarlet fever

Bullous pemphigoid – personal observation CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis, epididimitis, coldinduced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, conjunctivitis Ped Derm 33:602–614, 2016 Chronic granulomatous disease – translucent facial papules around eyes, nose, lips, cheeks; mimics lupus vulgaris NEJM 317:687–694, 1987; Chromobacterium violaceum Arch Ophthalmol 102:711–713, 1984 Cicatricial pemphigoid – red eyelid plaque AD 138:527–532, 2002 Dermatomyositis – eyelid edema JAAD 48:617–619, 2003; JAAD 47:755–765, 2002; heliotrope Epidermolysis bullosa acquisita – symblepharon BJ Opthalmol May 14, 2019; JAAD 70:795–819, 2014; localized periorbital edema AD 145:589–594, 2009 Graft vs. host disease – sclerodermatous graft vs. host reaction; periorbital papules JAAD 26:49–55, 1992; chronic GVHD – conjunc-

Eyelid Lesions tivitis, dry eye, cicatricial ectropion, symblepharon JAAD 70:795– 819, 2014 IgG4 disease – infiltration of eyelids (orbital pseudotumors) JAMA Derm 153:355–356, 2017 Immunodeficiency disorders – hypercupremia and decrease intracellular killing – blepharitis and pyoderma of the scalp

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  Cutaneous trauma   Epidermolysis bullosa    Focal dermal hypoplasia   Intrauterine infection    Intrauterine or perinatal trauma

Juvenile rheumatoid arthritis – Still's disease; evanescent rash; persistent pruritic papules and plaques; urticarial and urticarial-like rash, vesiculopustular eruptions, edema of the eyelids, widespread non-pruritic persistent erythema Medicine 96:e6318, 2017

Dacryocystocele – congenital blue/red firm nodule of medial canthus or medial lower eyelid due to congenital obstruction of nasolacrimal duct Ped Derm 28:70–72, 2011; JAAD 61:1088–1090, 2009   vs. Encephalocele   Nasal glioma   Infantile hemangioma   Congenital hemangioma   Dermoid cyst

Linear IgA disease (chronic bullous disease of childhood) – perioral, eyelids, ears, scalp, perineum, vulva; annular polycyclic bullae Ped Derm 15:108–111, 1998

Dermoid cyst - cystic nodule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.159

Lupus erythematosus – discoid lupus erythematosus – red plaque JAMA Derm 154:957–958, 2018; AD 138:527–532, 2002; BJD 121:727–741, 1989; JAAD 16:1259–1260, 1987; periorbital edema and erythema JAAD 26:334–338, 1992; red/swollen, sclerotic plaque AD 129:495–600, 1993; Am J Ophthalmol 98:32–36, 1984; systemic LE – red eyelid plaque AD 138:527–532, 2002

Nevus simplex (capillary ectasias) – glabella, eyelids, nose, upper lip, nape of neck

Ped Derm 1:134–142, 1983 Jung’s syndrome – atopic dermatitis, pyoderma, folliculitis, blepharitis Lancet ii:185–187, 1983

Pemphigus – El-Bagre endemic pemphigus; facial scaling and crusting, conjunctival injection, eyelid erythema and edema, ectropion, meibomitis JAAD 62:437–447, 2010; ocular pemphigus – lid margin ulceration JAAD 53:585–590, 2005 Pemphigus vulgaris, foliaceus, erythematosus Eur J Dermatol 11:141–143, 2001 PGM3 deficiency – autosomal recessive; dermatitis, conductive hearing loss, ataxia, myoclonus, narrow palpebral fissures; increased IgE; herpes simplex, molluscum contagiosum viral infections, sinopulmonary infections, chronic mucocutaneous candidiasis, developmental delay JAAD 73:355–364, 2015 Scleroderma – atrophy of bound down lower eyelids Ophth 89:1285–1288, 1982; morphea – ‘en coup de sabre’ with loss of eyelashes of upper eyelid Acta DV (Stockh) 63:75–77, 1983 STAT1 gain of function mutation – most common cause of chronic mucocutaneous candidiasis; demodicidosis with facial papulopustular eruptions, blepharitis, chalazion, dermatitis of the neck, nail dystrophy, congenital candidiasis Ped Derm 37:159–161, 2020 Adult onset Still’s disease – erythema of eyelids, erythema of knuckles, red plaques of legs JAAD 79:969–971, 2018; dermatomyositis-like Urticaria – systemic, contact, physical JAAD 47:755–765, 2002

CONGENITAL ANOMALIES Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis Ped Derm 29:756–758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985; most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails Ped Derm 30:387–388, 2013; JAAD 58:S104–106, 2008; JAAD 32:873–7, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985   Differential diagnosis:    Aplasia cutis congenita   Amniotic adhesions

DEGENERATIVE DISEASES Ectropion of the elderly Ophthalmology 92:120–127, 1985; scars Facial paralysis – ectropion

DRUG-INDUCED Accupril photoeruption – personal observation Acetretin – conjunctival granulation tissue; swollen upper and lower eyelids JAAD 58:S41–42, 2008 Brimonidine – unilateral ocular lichen planus Arq Bras Ofthalmol 82:236–238, 2019 Chemotherapy-related eccrine squamous syringometaplasia – red plaques of neck, axillae, groin, and lower eyelids; doxorubicin; bone marrow transplant regimen (cyclophosphamide, thiotepa, carboplatin) JAAD 64:1092–1103, 2011; AD 133:873–878, 1997 Corticosteroid (topical)-induced acne rosacea Docetaxel erythrodysesthesia – personal observation Etanercept-induced dermatomyositis – eyelid erythema, poikiloderma, acral erythema, paronychial erythema JAMA Derm 149:1204–1208, 2013 Fixed drug eruption – secondary to pseudoephedrine Cutis 41:339–340, 1988 Furosemide-induced bullous pemphigoid – personal observation Hepatitis B vaccine – necrolytic acral erythema; psoriasiform dermatitis, acral erythema and scale, cheilitis, verrucous papules of eyelids and around nose BJD 171:1255–1256, 2014 Imatinib – eccrine squamous syringometaplasia; red eyelid papules JAAD 55:S58–59, 2006; edema of eyelids and face JAAD 58:545– 570, 2008 Isotretinoin embryopathy – small or absent ears, microphthalmia, micrognathia, deafness, limb reduction or duplication Ped Derm 29:774–776, 2012 Methotrexate-associated lymphoproliferative disorder – red papules and plaques of nose, cheeks, eyelids JAAD 56:686–690, 2007 Sunitinib (multikinase inhibitor) – periorbital and facial edema JAAD 58:545–570, 2008 Thiotepa eyedrops – periorbital depigmentation AD 115:973–974, 1979

352 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

EXOGENOUS AGENTS Cosmetic creams irritant contact dermatitis – personal observation Fixed food eruption – lactose JAAD 52:370–371, 2005 Iododerma in chronic renal failure – edema of eyelids; pustulovesicular eruption, pustules, pseudovesicles, marked edema of face and eyelids, vegetative plaques AD 140:1393–1398, 2004; JAAD 36:1014–1016, 1997; Clin Exp Dermatol 15:232–233, 1990; BJD 97:567–569, 1977 Irritant contact dermatitis – eye shadow, eye shadow setting creams, eye-liners, mascaras, artificial eyelashes, eyebrow pencils, eye makeup removers JAAD 47:755–765, 2002; The Clinical Management of Itching; Parthenon; p. 117, 2000

Caterpillar dermatitis – urticarial papules surmounted by vesicles, eyelid edema; gypsy moth caterpillar – conjunctivitis with eyelid dermatitis NEJM 306:1301–1302, 1982 Cellulitis – including association with sinusitis JAAD 48:617–619, 2003; J Eur Acad Dermatol Venereol 11:74–77, 1998; orbital cellulitis Surv Ophthalmol 63:534–553, 2018; preseptal cellulitis Disease A Month 63:30–32, 2017 Chagas’ disease – American trypanosomiasis (Trypanosoma cruzi); Romana’s sign – unilateral edema of the eyelids and inflammation of the lacrimal gland Chancriform pyoderma (Staphylococcus aureus) – ulcer with indurated base; eyelid, near mouth, genital AD 87:736–739, 1963

Mercury – in skin folds and eyelids JAAD 39:524–525, 1998; mercurial ointments – periorbital depigmentation

Coccidioidomycosis – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.11

Paraffinoma – facial nodules and eyelid edema JAAD 56:S127–128, 2007

Cysticercosis (Taenia solium) (Cysticercus cellulosae) AD 89:319– 320, 1973

Pseudolymphoma, lymphomatoid contact dermatitis – upper eyelid nodules BJD 143:411–414, 2000

Demodex folliculorum – demodex blepharitis Ann DV 113:1047– 1058, 1986; periorbital papular dermatitis JAAD 60:453–462, 2009

Silicone - breast implant; silicone granulomas, chronic eyelid edema Ophthal Plast Reconstr Surg 14:182–188, 1998; metastatic silicone granuloma – eyelid papules, eyelid edema AD 138:537–538, 2002; eyelid augmentation – nodules BJD 152:1064–1065, 2005

Dirofilariasis, subcutaneous (migratory nodules) – eyelid, scrotum, breast, arm, leg, conjunctiva JAAD 73:929–944, 2015; JAAD 35:260–262, 1996

INFECTIONS AND INFESTATIONS Abscess – Pott’s puffy tumor – sinusitis with frontal bone osteomyelitis and epidural abscess; swelling of upper eyelid JAMA Derm 151:1261–1263, 2015 Actinomycosis – proptosis and eyelid swelling BJ Ophthalmol 76:505–506, 1992; tender swelling of lower eyelid Indian Pathol Microbiol 54:661–663, 2011 Anthrax – Bacillus anthracis; swollen eyelids; malignant pustule; painless ulcer with vesicular lesions; face, neck, hands, fingers, arms, foot, knee; starts as painless erythema evolving into papule then into multiple vesicles or bulla on red base; then ulcer with hemorrhagic crust (eschar) with edema and erythema with small vesicles; edema of surrounding skin; takes six weeks to heal; edema of eyelids, lips, perioral area; slaughtering or milking of ill cows, sheep, or goats; handling of raw meat Ped Derm 27:600–606, 2010; Ped Derm 18:456–457, 2001; Br J Opthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355– 361, 1981; preseptal cellulitis and cicatricial ectropion Acta Ophthalmol Scand 79:208–209, 2001; Br J Opthalmol 76:753–754, 1992; Ophthalmic Physiol Opt 10:300–301, 1990 Ascariasis – unilateral eyelid edema Klin Oczna 97:346–347, 1995 (Polish) Bacterial sinusitis – eyelid edema Bacillary angiomatosis SKINmed 4:215, 2005 Blister beetle – periorbital dermatitis and keratoconjunctivitis Eye 12:883–885, 1998 Disseminated botryomycosis – due to Staphylococcus aureus; disseminated pustules of nose, papules of eyelids, eschars of extremities J Drugs Dermatol 13:976–78, 2014 Brown recluse spider bite – dermonecrotic lesion with periorbital edema Turk J Pediatr 53:87–90, 2011 Candidiasis, including chronic mucocutaneous candidiasis – blepharitis Cat scratch disease – oculoglandular granuloma; simulating lymphoma Cancer 50:584–586, 1982

Epstein-Barr virus (HHV4) – primary cutaneous Epstein-Barr virus-related lymphoproliferative disorders; eyelid nodule JAAD 58:74–80, 2008 Erysipelas/cellulitis – eyelid erythema, edema JAAD 48:617–619, 2003 Folliculitis Gonorrheal conjunctivitis – profuse purulent discharge; swollen hemorrhagic eyelids Halfbeak fish – ptosis of upper eyelid due to immobilization of levator and superior rectus muscle by mandibles of halfbeak fish after swimming in the Red Sea NEJM 373:1153, 2015 Herpes simplex;- eczema herpeticum (Kaposi’s varicelliform eruption) Arch Dis Child 60:338–343, 1985; chronic herpes simplex – personal observation Herpes zoster Human papilloma virus Int J Oncol 54:1503–1510, 2019; Arch Pathol Lab Med 142:708–710, 2018 Human T-lymphotropic virus type 1-associated infective dermatitis – chronic relapsing dermatitis; severe red and exudative dermatitis with scaling and crusting of scalp, forehead, eyelids, paranasal area, neck, retroauricular, external ear, axillae, groin; chronic watery nasal discharge, crusting of anterior nares, blepharoconjunctivitis; generalized fine popular rash with lymph nodes; onset of rash at age 2 years; most common form of transmission is breast feeding; harbinger of development of adult T-cell lymphotropic leukemia and HTLV-1 associated myelopathy (HAM)/tropical spastic paralysis (TSP); Jamaica, Senegal, Brazil (endemic areas) JAAD 64:152– 160, 2011; Lancet 336:1345–1347, 1990; Proc Natl Acad Sci USA 77:7415–7419, 1980; BJD 79:229–236, 1967; BJD 78:93–100, 1966 Impetigo contagiosa Infectious mononucleosis (Epstein-Barr virus) – eyelid edema in 50% of patients; periorbital and eyelid edema Cutis 47:323–324, 1991; Pediatrics 75:1003–1010, 1985 Leishmaniasis – swollen eyelid (Old World leishmaniasis) JAAD 73:897–908, 2015; Ophthalmology 107:169–172, 2000 Leprosy – tuberculoid; blepharochalasis, ectropion, entropion, lagophthalmos (inability to completely close the lids) Clinics in Dermatol 33:8–18, 2015

Eyelid Lesions Loiasis – Loa; Chrysops (deer fly, horse fly, mangrove fly) – adult worms in conjunctiva with unilateral palpebral edema AD 108:835– 836, 1973 Molluscum contagiosum – giant tumor Ethiop Med J 38:125–130, 2000; Am J Ophthalmol 124:240–241, 1997; Pediatr AIDS HIV Infect 7:43–46, 1996; papule; solitary ulcerating mass Saudi J Ophthalmol 32:338–340, 2018 Mucormycosis – ptosis with upper eyelid edema and necrosis JAMA 309:2382–2383, 2013; papule, pustule, necrotic ulcer Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.169; rhino-orbital-cerebral mucormycosis – red eyelids with black necrotic plaque of medial eyelids Cutis 94:168, 195–196, 2014 Mycobacterium avium – red nodule Ped Derm 33:196–199, 2016 Mycobacterium haemophilum – red nodule Ped Derm 33:196–199, 2016 Mycobacterium tuberculosis – tuberculous chancre – ulceration and edema of the lids Pakistan J Ophthalmol 4:37–40, 1988; lupus vulgaris Ophthalmology 106:1990–1993, 1999; tuberculous abscess Am J Ophthalmol 121:717–718, 1996; eyelid draining sinus, “chalazion”; cold abscess; lupus vulgaris Natl Med J India 31:279– 280, 2018 Mycoplasma pneumonia (MIRM) – erosive eyelid dermatitis, hemorrhagic erosive cheilitis, penile erosions, perianal erosions JAMA Derm 156:144–150, 2020 Myiasis – resemble hordeolum Korean J Ophthalmol 13:138–140, 1999; Dermatobia hominis – edema and erythema of eyelid Ped Inf Dis 21:82–83, 2002; abscess-like lesion (Cuterebra) Cutis 86:85– 86, 2010; Hypoderma tarandi (bumblebee-like fly) attaches eggs on hair of reindeer (caribou) (Rangifer tarandus) in Norway and Sweden; facial skin colored nodules; red papule of eyelid with edema of eyelid NEJM 367:2456–2457, 2012 Necrotizing fasciitis (streptococcal gangrene) – personal observation; Br J Ophthalmol 94:1577–1585, 2010 New Jersey polyoma virus – personal observation JAAD 72;538– 540, 2015 North American blastomycosis – papule Ophthal Plast Reconstr Surg 8:143–149, 1992; Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 169 Orf Cutis 20:109–111, 1977 Paracoccioidomycosis Mycopathologia 140:29–33, 1997 Pediculosis (Phthirus pubis) – blepharitis Am J Dis Child 138:1079– 1080, 1984 Pseudomonas sepsis – gangrenous eyelids (noma neonatorum) Lancet 2:289–291, 1978; necrotizing fasciitis Singapore Med J 5:e51–53, 2010; ecthyma gangrenosum of eyelid Ped Inf Dis 21:83–85, 2002 Pythium insidiosum (pythiosis) (alga) (aquatic oocyte) – necrotizing hemorrhagic plaque; ascending gangrene of legs; Thailand; painful subcutaneous nodules, eyelid swelling and periorbital cellulitis, facial swelling, ulcer of arm or leg, pustules evolving into ulcers BJD 175:394–397, 2016; J Infect Dis 159:274–280, 1989 Rhinosporidiosis – conjunctivitis and eversions of eyelid Arch Otolaryngol 102:308–312, 1976 Sparganosis (Sparganum proliferum) – undercooked meat; eyelid mass; solitary slow growing migratory subcutaneous nodule of anterior abdomen JAAD 73:929–944, 2015

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Styes, staphylococcal – personal observation Syphilis, secondary; extragenital primary chancre of lower eyelid; alopecia of eyebrows and eyelashes Acta Dermatosifilogr 110:e12, 2019 Tinea faciei – Trichophyton mentagrophytes – red plaque of eyelid with pustules Ped Derm 34:711–712, 2017; Cutis 17:913–915, 1976; in newborn Minerva Pediatr 53:29–32, 2001; steroid modified tinea – may resemble stye Trichinosis – periorbital edema; initially have abdominal pain and diarrhea Clin Inf Dis 59:1750–1756, 2014; J Egypt Soc Parasitol 27:529–538, 1997 Trypanosomiasis Vaccinia – autoinoculation ; eczema vaccinatum Ophthalmol 111:2086–2093, 2004; MMWR Recomm Rep 52:1–28, 2003 Varicella Clin Pediatr 23:434–436, 1984 Verruga peruana Am J Trop Med Hyg 50:143–144, 1994 Warts JAAD 47:908–913, 2002 Yaws – papules

INFILTRATIVE DISORDERS Amyloidosis – primary systemic; purpura JAMA Derm 153:593–594, 2017; papules Cutis 80:193–200, 2007; Postgrad Med J 64:696– 698, 1988; Clin Exp Dermatol 4:517–536, 1979; diffuse eyelid swelling J Dermatol 19:113–118, 1992; ptosis JAAD 70:795–819, 2014; conjunctival amyloidosis with unilateral upper and lower eyelid edema Korean J Ophthalmol 15:38–40, 2001; familial amyloidosis with transthyretin mutation – personal observation Benign cephalic histiocytosis – eyelid papules; mimic flat warts, Spitz nevi, juvenile xanthogranuloma, Langerhans cell histiocytosis, urticaria pigmentosum, generalized eruptive histiocytosis, sarcoid JAAD 47:908–913, 2002; AD 135:1267–1272, 1999 Colloid milium – juvenile colloid milium – eyelids, nose, gingiva, conjunctiva JAAD 49:1185–1188, 2003; Clin Exp Dermatol 25:138–140, 2000 Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100; xanthoma and xanthelasma-­like lesions (red-brown-yellow papules and plaques); flat wart-like papules of face; lesions occur in folds; skin becomes slack with atrophy of folds and face; also lesions of eyelids, axillae, groin, neck; pretibial dermopathy, pigmented lesions of lips and buccal mucosa; long bone sclerosis; diabetes insipidus, painless exophthalmos, retroperitoneal fibrosis, renal (hairy kidneys), cerebellar syndrome, and pulmonary histiocytic infiltration; differential diagnosis includes Graves’ disease, Hashimoto’s thyroiditis, sarcoid JAMA Derm 155:483–484, 2019; Rheum Dis Clin NA 39:299–311, 2013; J Cutan Pathol 38:280–285, 2011; Int J Urol 15:455–456, 2008; Austral J Dermatol 44:194–198, 2003; JAAD 57:1031–1045, 2007; AD 143:952–953, 2007; Hautarzt 52:510–517, 2001; Medicine (Baltimore) 75:157–169, 1996; Virchow Arch Pathol Anat 279:541–542, 1930 Focal mucinosis – eyelid papule Generalized eruptive histiocytosis Am J Dermatopathol March, 2015; An Bras Dermatol 88:105–108, 2013; JAAD 50:116–120, 2004; JAAD 47:908–913, 2002; Am J Dermatopathol 18:490–504, 1996; AD 88:586–596, 1963

Sporotrichosis Microorganisms Dec 21, 2019

Primary and secondary intralymphatic histiocytosis – red plaque of eyelid; red patch of back; livedo reticularis JAAD 70:927–933, 2014

Staphylococcal blepharitis with associated conjunctivitis Arch Ophthalmol 95:812–816, 1977

Jessner’s lymphocytic infiltrate red eyelid plaque AD 138:527–532, 2002

354 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Juvenile xanthogranuloma – papule JAAD 36:355–367, 1997; adult Trans Am Ophtalmol Soc 91:99–129, 1993; plaque-type juvenile xanthogranuloma – red plaques of face; swollen eyelids with periorbital edema JAAD 59:S56–57, 2008 Langerhans cell histiocytosis – infiltrated red plaque – urticating Langerhans cell histiocytosis JAAD 14:867, 873, 1986; swollen eyelids, exophthalmos, palpable mass BMC Ophthalmol 19:263, 2019 Mastocytoma Virchows Arch A Pathol Anat Histopathol 412:31–36, 1987 Rosai-Dorfman disease – bilateral eyelid edema Ped Derm 26:633–635, 2009; xanthomatous lesions Int J Dermatol 56:981– 992, 2017 Sea blue histiocytosis – facial macular brown hyperpigmentation; nodules of face, trunk, hands, and feet; eyelid infiltration; puffy face; leonine facies JAAD 57:1031–1045, 2007; eyelid swelling and facial nodules Dermatologica 174:39–44, 1987 Self-healing juvenile cutaneous mucinosis JAAD 50:S97–100, 2004 Xanthogranuloma AD 137:1253–1255, 2001; periorbital xanthogranulomas (adult-onset asthma with periocular xanthogranulomas) – hyperpigmented indurated nodules of upper and lower eyelids (swollen eyelids); associated with asthma AD 147:1230– 1231, 2011; Arch Pathol Lab Med 133:1994–1997, 2009; Br J Ophthalmol 90:602–608, 2006; Trans Am Ophthalmol Soc 91:99– 129, 1993; recurrent eyelid swelling Arch Soc Esp Oftalmol 94:248–251, 2019 Xanthoma disseminatum – intertriginous violaceous-yellow purpuric papules, confluent xanthomatous plaques in axillae, groin, other folds; face, eyelids, chest upper back, globe of eyeball AD 147:459– 464, 2011; perioral papules; eyelid papules; scrotal papules; intertrigo BJD 170:1177–1181, 2014

INFLAMMATORY DISEASES Blepharitis granulomatosa – edema AD 120:1141–1142, 1984 Chronic blepharitis – red eyelid plaque AD 138:527–532, 2002 Chronic dacryoadenitis – eyelid edema Jpn J Ophthalmol 43:109– 112, 1999 Frontal sinus fistula tract – ulcerated eyelid AD 148:1411–1416, 2012 Idiopathic facial aseptic granuloma – eyelid papulonodule AD 137:1253–1255, 2001 Kikuchi’s disease – eyelid edema Ann DV 126:826–828, 1999 Lacrimal canaliculitis – personal observation Lipogranulomas – orbital lipogranulomas – yellow eyelid papules Ophthal Plast Reconstr Surg 15:438–441, 1999; JAAD 37:839–842, 1997 Malacoplakia – papule Ophthalmology 95:61–68, 1988 Marginal blepharitis Meibomitis – personal observation Nodular fasciitis Ophthal Plast Reconstr Surg 15:139–142, 1999; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.147 Orbital lipogranulomas – yellow eyelid papules Orbital myositis – erythema and edema Aust N Z J Med 17:585– 591, 1987 Orofacial granulomatosis – facial edema with swelling of lips, cheeks, eyelids, forehead, mucosal tags, mucosal cobblestoning, gingivitis, oral aphthae BJD 143:1119–1121, 2000

Pseudolymphoma – as manifestation of allergic contact dermatitis (upper eyelid nodules) BJD 143:411–414, 2000 Pyoderma gangrenosum JAMA Derm 152:491–492, 2016; Ped Derm 22:543–545, 2005; Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988; upper eyelid BMJ Case Rep July 8, 2019 Pyostomatitis vegetans – personal observation Sarcoid Can J Ophthalmol 25:256–259, 1990; papules; destructive eyelid lesions Ophthal Plas Reconstr Surg 17:123–125, 2001; eyelid swelling, palpable mass Am J Ophthalmol 44:769–775, 2007 Stevens-Johnson syndrome/toxic epidermal necrolysis BJD 174:1194–1227, 2016; scarring of upper lid JAAD 25:69–79, 1991; Toxic epidermal necrolysis – begins with inflammation of the eyelids – erosions of eyelids BJD 174:1194–1227, 2016; BJD 68:355–361, 1956 Vernal keratoconjunctivitis – confluent cobblestoned papillae in upper palpebral conjunctivae NEJM 370:1636, 2014

METABOLIC DISEASES Acrodermatitis enteropathica – blepharitis Ped Derm 19:426–431, 2002 Acromegaly – edematous thick eyelids Angiokeratoma corporis diffusum (Fabry’s disease) (alpha galactosidase A) – X-linked recessive; upper eyelid edema NEJM 276:1163– 1167, 1967 Calcinosis cutis – on eyelid margin in chronic renal failure Ophthalmol Plast Reconstr Surg 33:304–306, 2017; Am J Ophthalmol 107:556–557, 1989; subepidermal calcified nodule; papule Ped Derm 18:227–229, 2001 Congenital disorders of glycosylation (CDG-Ie) – eyelid telangiectasia, hemangiomas, inverted nipples, microcephaly; neurologic abnormalities; dolichol-phosphate-mannose synthase Ped Derm 22:457–460, 2005 Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 167:988–900, 2012 Congestive heart failure – eyelid edema JAAD 48:617–619, 2003 Hyperthyroidism – unilateral eyelid edema JAAD 48:617–619, 2003; hyperpigmentation of eyelids (Jellinek’s sign) JAAD 47:438, 2002; BJD 76:126–139, 1964; Grave’s disease – proptosis due to retraction of eyelids Hypoalbuminemia – eyelid edema JAAD 48:617–619, 2003 Kwashiorkor – personal observation Myotonic dystrophy – ptosis (blepharochalasis?) JAAD 50:S1–3, 2004 Myxedema (hypothyroidism) – eyelid edema JAAD 48:617–619, 2003 Necrobiosis lipoidica diabeticorum Ochronosis – hyperpigmentation of eyelids with blue tarsal plates of eyelids Am J Med 34:813–838, 1963 Pellagra – eyelid edema Cutis 69:96–98, 2002

Eyelid Lesions

355

Porphyria – congenital erythropoietic porphyria – ectropion Semin Liver Dis 2:154–63, 1982; erythropoietic porphyria – mutilation of eyelids

Endocrine mucin-producing sweat gland carcinoma – red eyelid papule Cutis 93:47–49, 2014

Pregnancy – eyelid edema

Epidermoid cyst – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.157

Xanthomas – diffuse planar, tuberous, xanthelasma – yellow eyelid xanthelasma palpebrum – swollen lids Cutis 41:113–114, 1988; generalized plane xanthomas; deforming xanthelasma – personal observation Zinc deficiency, acquired – blepharitis JAAD 69:616–624, 2013

NEOPLASTIC DISEASES Actinic keratosis - papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999,p.19 Adenoid cystic carcinoma, primary cutaneous – eyelid papule JAAD 58:636–641, 2008 Angiosarcoma – yellow plaques of eyelids Aust NZ J Opththalmol 23:69–72, 1995; periorbital edema and edematous eyelids AD 148:683–685, 2012; Am J Ophthalmol 125:870–871, 1998; Aust N Z J Ophthalmol 23:69–72, 1995; eyelid edema Hautarzt 51:419–422, 2000; eyelid papule nodule AD 121:549–550, 1985; yellow plaques of eyelids JAAD 34:308–310, 1996; nodule AD 121:549–550, 1985 Apocrine cystadenoma - personal observation Apocrine gland carcinoma Br J Plast Surg 42:598–602, 1989 Apocrine hidrocystomas – string of pearls JAAD 10:922–925, 1984 Atypical lymphoid hyperplasia – yellow eyelid papules JAAD 37:839–842, 1997 Basal cell carcinoma AD 140:1003–1008, 2004; Ophthalmologica 212 Supp1:40–41, 1998; JAAD 25:685–690, 1991; J Derm Surg Oncol 11:1203–1207, 1985; Blue nevus – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.90–91 Bowen's disease Chalazion – yellow, skin colored or red papule or nodule Ophthalmology 87:218–221, 1980 Chondroid syringoma J Postgrad Med 42:125–126, 1996 Conjunctival congenital cysts Klin Monatsbl Augenheilkd 213:117– 120, 1998 Cutaneous horn – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.15 Cutaneous lymphoproliferative disorder associated with infectious mononucleosis – ulcerated eyelid nodule Ped Derm 28:149–155, 2011

Epidermal nevus, including epidermal nevus syndrome

Epidermolytic acanthoma AD 101:220–223, 1970 Epstein-Barr virus associated lymphoproliferative lesions – eyelid edema BJD 151:372–380, 2004 Eruptive vellus hair cysts – skin colored, red, white, blue, yellow eyelid papules Ped Derm 19:26–27, 2002 Ethmoid sinus mucocele – ocular edema, proptosis Clin Exp Ophthalmol Nov 26, 2019 Extramammary Paget’s disease JAAD 47:S229–235, 2002 Fibrosarcoma – juvenile fibrosarcoma Arch Ophthalmol 101:253– 259, 1983; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.148 Giant cell angiofibroma Ophthalmology 106:1223–1229, 1999 Granular cell tumor – eyelid papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.179 Hair follicle hamartoma – edematous lids BJD 143:1103–1105, 2000 Hidradenoma papilliferum JAAD 41:115–118, 1999; AD 117:55–56, 1981 Hidrocystoma – eccrine J Dermatol 21:490–493, 1994; JAAD 26:780–782, 1992; apocrine – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.153 Hydroa vacciniforme-like Epstein-Barr virus-associated lymphoproliferative disease – edema of cheeks, eyelids, ears, and lips Ped Derm 29:96–100, 2012 Intra-epidermal carcinoma of the eyelid margin BJD 93:239–252, 1975 Inverted follicular keratosis – papule Ophthalmology 94:1465–1468, 1987; Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.9 Kaposi's sarcoma – eyelid papules and pulmonary infiltrates in HIV disease with immune reconstitution syndrome NEJM 369;1152– 1161, 2013; JAAD 40:312–314, 1999; Ann Ophthalmol 14:497–499, 1982; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.121

Dacryocystocele, neonatal – neonatal red cystic nodule of medial lower eyelid Ped Derm 34:209–211, 2017

Keratoacanthomas Ophthalmic Surg 17:565–569, 1986; Grzybowski eruptive keratoacanthomas; ectropion BJD 147:793–796, 2002; BJD 142:800–803, 2000; eruptive – periorbital papules JAAD 37:478– 480, 1997; solitary papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.13

Dermatofibroma Orbit 38:274–278, 2019

Large cell acanthoma Arch Ophthalmol 109:1433–1434, 1991

Dermoid cyst

Leiomyoma of the lacrimal sac – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.189

Desmoplastic trichilemmoma – white papule of eyelid; lip papule JAAD 76:S22–24, 2017 Eccrine acrospiroma Eur J Ophthalmol 1:187–193, 1991; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.55 Eccrine spiradenomas – linear J Eur Acad Dermatol Venereol 15:163–166, 2000 Eccrine sweat gland carcinoma – papule or indurated thickening of eyelid Int Ophthalmol Clin 22:1–22, 1982 Embryonal rhabdomyosarcoma AD 138:689–694, 2002

Lentigo maligna – macule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.85 Leukemia cutis – acute myelogenous leukemia – eyelid nodule JAAD 40:966–978, 1999; chloroma – personal observation Lipoblastoma – yellow nodule of eyelid Am J Dermatopathol 12:408–411, 1990 Lymphoma – edematous redundant eyelid skin – folliculotropic cutaneous T-cell lymphoma JAMA Derm 156:811–812, 2020; Cutis

356 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 57:437–440, 1996; cutaneous T-cell lymphoma – ectropion; eyelid nodules JAAD 70:205–220, 2014; JAAD 60:359–375, 2009; cutaneous T-cell lymphoma (Sezary syndrome) Semin Oncol 26:276–289, 1999; JAAD 27:427–433, 1992; JAAD 41:254–259, 1999; B-cell, T-cell – papules, plaques, and tumors Br J Ophthalmol 69:861–864, 1985; gastric MALT-lymphoma Klin Monatsbl Augenheilkd 217:133–135, 2000; eyelid ulcers AD 138:527–532, 2002; CD4+ small to medium size pleomorphic T-cell lymphoma – red swollen eyelid with alopecia of eyebrow Ped Derm 30:595–599, 2013; post-transplant lymphoma JAAD 81:600–602, 2019

Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.99

Lymphomatoid papulosis – facial and eyelid papules Ped Derm 31:103–104, 2014

Nevus of Ota (nevus fuscoceruleus ophthalmomaxillaris) BJD 67:317–319, 1955

Marginal cysts – occluded glands of Moll; painless white or yellow cyst of lower eyelid close to lacrimal punctum

Nevus sebaceus

Meibomian gland cancer

Oncocytoma – bright red or yellow papule Arch Ophthalmol 102:263–265, 1984

Melanoacanthoma AD 105:898–899, 1972 Melanocytic nevus – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.77; divided nevus Ped Derm 22:427–429, 2005; Br J Ophthalmol 72:198–201, 1988; periorbital congenital nevi with ankyloblepharon Ped Derm 18:31–33, 2001 Melanoma – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.93; desmoplastic melanoma Ann Ophthalmol 14:141–143, 1982; lentigo maligna and lentigo maligna melanoma – personal observation Merkel cell carcinoma – red papule mimicking chalazion Cutis 97:290–295, 2016; JAAD 58:375–381, 2008; Am J Ophthalmol 121:331–332, 1996; Aust N Z J Ophthlmol 24:377–380, 1996; J R Coll Surg Edin 36:129–130, 1991; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.101; epidermotropic Merkel cell carcinoma – red eyelid papules JAAD 62:463–468, 2010 Metastases – induration, ulcer, or painless nodule Arch Opthalmol 92:276–286, 1974; breast cancer AD 142:1351–1356, 2006; Cutis 31:411–415, 1983; Ophthalmology 94:667–670, 1987; gastric Eur J Ophthalmol 2:3–9, 1992; renal cell, carcinoid – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.135; JAAD 36:997–998, 1996; melanoma Ophthalmol Surg Lasers 29:993–995, 1998 Microcystic adnexal carcinoma JAAD 45:283–285, 2001; JAAD 41:225–231, 1999 Milia- including milia en plaque Ped Derm 26:717–720, 2009; Ped Derm 15:282–284, 1998 Mucinous eccrine carcinoma (primary cutaneous mucinous carcinoma of skin) – eyelid papules AD 148:849–854, 2012; JAAD 49:941–943, 2003; AD 136:1409–1414, 2000; Dermatol Surg 25:566–568, 1999; JAAD 36:323–326, 1997; eyelid and scalp Am J Surg Pathol 29:784–782, 2005 Mucocoele of frontal or ethmoid sinus – subcutaneous nodule Arch Ophthalmol 81:683–688, 1969 Mucoepidermoid carcinoma – eyelid nodule Derm Surg 27:1046– 1048, 2001 Myeloid sarcoma – may be seen as isolated finding or as part of myelodysplastic syndrome, myeloproliferative disease, or acute myelogenous leukemia Int J Ophthalmol 18:1359–1361, 2019; NEJM 369:2332, 2013 Myospherulosis Am J Rhinol 11:345–347, 1997 Myxoma – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.149 Neurilemmoma (Schwannoma) – resembling chalazion Arch Ophthalmol 102:1650, 1984; papule Eyelid and Conjunctival

Neurofibromas – papules Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.97 Neuroma – palisaded encapsulated neuroma Br J Ophthalmol 85:949–951, 2001 Neurothekeoma JAAPOS 20:374–376, 2016 Nevus comedonicus – ptosis, ectropion Am J Ophthalmol Case Reports Dec 17, 2019

Nevus spilus, divided J Cutan Pathol 6:507–512, 1979

Papilloma – sessile, pedunculated papule; ulcerated J Ophthalmic Vis Res 14:509–512, 2019 Perforating follicular hybrid cyst (pilomatrixoma and steatocystoma) of inner eyelid (tarsus) JAAD 48:S33–34, 2003 Pilomatrixoma – papule Cutis 69:23–24, 2002; Ophthal Plast Reconstr Surg 15:185–189, 1999; Ophthalmologica 90:766–769, 1993 Plasmacytoma – primary plasmacytoma Med Oncol 17:74–75, 2000; papule; retrobulbar NEJM 345:1917, 2001 Pleomorphic adenoma (benign mixed tumor) – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.59 Pseudoepitheliomatous hyperplasia – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.11 Retention cyst from glands of Zeis Rhabdomyoma Am J Dermatopathol 22:264–267, 2000 Sebaceous adenoma – papule J Cutan Pathol 11:396–414, 1984 Sebaceous carcinoma – red eyelid papule (mimics chalazion) JAAD 61:549–560, 2009; JAAD 53:925–927, 2005; Am J Surg Pathol 2:305–311, 1978; Trans Am Acad Ophthalmol Otol 72:619–640, 1968; late ulceration Sem Cut Med Surg 21:159–165, 2002; Br J Ophthalmol 82:1049–1055, 1998; Br J Plast Surg 48:93–96, 1995; JAAD 25:685–690, 1991; J Derm Surg Oncol 11:260–264, 1985; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.40–41; morpheic plaque, blepharitis JAAD 14:668–673, 1986 Seborrheic keratosis – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.7 Signet ring cell carcinoma, primary cutaneous – eyelid papules JAAD 54:532–536, 2006 Smooth muscle hamartoma Am J Ophthalmol 128:643–644, 1999 Spitz nevus AD 137:1253–1255, 2001; agminated Spitz nevi Ped Derm 6:114–117, 1989 Squamous cell carcinoma – papule Arch Ophthalmol 118:422–424, 2000; Ophthal Plast Reconstr Surg 10:153–159, 1994; JAAD 25:685–690, 1991; adenoid SCC Am J Ophthalmol 99:291–297, 1985 Squamous cell carcinoma of the lacrimal sac – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.185 Syringocystadenoma papilliferum Ophthalmology 88:1175–1181, 1981; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.55

Eyelid Lesions

357

Syringomas Derm Surg 25:136–139, 1999; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.53; giant syringomas – eyelid papules Cutis 89:23–24, 2012

PRIMARY CUTANEOUS DISEASES

Syringomatous carcinoma (malignant syringoma) Br J Ophthalmol 81:668–672, 1997; Ophthalmology 91:987–990, 1984

Acne rosacea – blepharitis (desquamation and erythema) BJD 65:458–463, 1953; styes, chalazion JAAD 70:795–819, 2014; periorbital chronic edema Arch Ophthalmol 108:561–563, 1990; acne agminata (granulomatous rosacea) – monomorphic brown papules of chin, cheeks, eyelids Cutis 82:111–112, 2008; BJD 134:1098–1100, 1996; red eyelid plaque AD 138:527–532, 2002; acne rosacea cysts of eyelid; lupus miliaris disseminata faciei (granulomatous rosacea) – eyelid papules Dermatol Ther July 30, 2017; JAAD 71:410–412, 2014; ocular rosacea with meibomitis – personal observation

Transient myeloproliferative disorder associated with mosaicism for trisomy 21 – vesiculopustular rash NEJM 348:2557–2566, 2003; in trisomy 21 or normal patients; periorbital vesiculopustules, red papules, crusted papules, and ulcers; with periorbital edema Ped Derm 21:551–554, 2004 Transitional cell carcinoma of the lacrimal sac papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.185

Acanthosis nigricans Ophthal Plast Reconstr Surg 10:49–50, 1994; Am J Ophthalmol 115:42–45, 1993

Trichilemmomas Arch Ophthalmol 98:844–847, 1980; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.69; thickened eyelids along lash margin – trichilemmomas in Cowden's disease

Ankyloblepharon filiforme adnatum – adhesions between upper and lower eyelids; type I – isolated; type II – with myelomeningocele, patent ductus arteriosus, or imperforate anus; type III – pterygiumpopliteal syndrome; Hay-Wells syndrome; type IV – labiopalatine fissures; type V – trisomy 18 Ped Derm 27:207–208, 2010

Trichoadenoma – papule Am J Ophthalmol 126:846–848, 1998; comedo-like Ophthalmic Plast Reconstr Surg 35:e94–95, 2015

Atopic dermatitis – eyelids lichenified, inflamed, scaly, crusted; Dennie-Morgan folds

Trichoepithelioma Eye 12:43–46, 1998; Ophthalmology 93:531–533, 1986; solitary or multiple – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.65

Blepharochalasis Br J Ophthalmol 72:863–867, 1988; Cutis 45:91–94, 1990; Can J Ophthalmol 27:10–15, 1992; AD 115:479–481, 1979; recurrent eyelid edema, ptosis AD 145:498– 499, 2009  Ascher's syndrome – blepharochalasis with progressive enlargement of upper lip; increased thickness of eyelids JAAD 29:650– 651, 1993; Ped Derm 8:122–123, 1991; BJD 66:129–138, 1954   Chronic dermatitis   Cutis laxa   Familial systemic amyloid   Floppy eyelid syndrome   Granulomatous slack skin syndrome (CTCL)  Hughes syndrome (acromegaloid features and thickened oral mucosa) J Med Genet 22:119–125, 1985  Idiopathic   Meretoja's syndrome

Trichofolliculoma – papule Ophthalmol Plast Reconstr Surg 35:e74–76, 2019

PARANEOPLASTIC DISORDERS Acanthosis nigricans BJD 153:667–668, 2005 Diffuse plane xanthomatosis – flat yellow plaques of eyelids, neck, trunk, buttocks, flexures AD 93:639–646, 1966 Hypertrichosis lanuginosa acquisita (malignant down) – in mild forms, confined to face – starts on nose and eyelids; lung, colon carcinomas most common; also breast, gall bladder, uterus, urinary bladder if accompanied by acanthosis nigricans, the malignancy is always an adenocarcinoma Can Med Assoc 118:1090–1096, 1978 Necrobiotic xanthogranuloma with paraproteinemia – yellow eyelid papules AD 145:279–284, 2009; Hautarzt 46:330–334, 1995; Arch Ophthalmol 101:6063, 1983; JAAD 3:257–270, 1980 Paraneoplastic pemphigus – bilateral eyelid ulcerations Ocul Immunol Inflamm 26:265–268, 2018; erythema, erosions, crusting BJD 160:468–470, 2009

PHOTODERMATOSES Chronic actinic dermatitis Dermatoheliosis – ectropion Favre-Racouchot syndrome (actinic comedonal plaque) Am J Ophthalmol 96:687–688, 1983 Hydroa vacciniforme (Epstein-Barr virus-related) – red macules progress to tender papules or vesiculopapules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of cheeks, eyelids, ears, and lips AD 142:587–595, 2006

Blepharophimosis  Cleft lip-palate, blepharophimosis, lagophthalmos, hypertelorism Am J Med Genet 10:409–412, 1981   Marden-Walker syndrome J Med Genet 18:50–53, 1981  Schwartz-Jampel syndrome (chondrodystrophic myotonia) Arch Neurol 22:455–462, 1972 Blepharospasm Childhood granulomatous perioral (orbital) dermatitis – papules AD 128:1395–1400, 1992 Collodion baby (lamellar desquamation of the newborn) – ectropion eclabium; congenital erythroderma, deformed ears, alopecia; mutation in ABCA12 BJD 166:218–221, 2012 Dermatochalasis – lax eyelid skin in elderly Dowling-Degos disease – comedone-like lesions on upper eyelids Ectopic eyelashes (cilia) – of anterior tarsal plate on upper eyelid Ped Derm 28:55–56, 2011; Ped Derm 24:433–435, 2007 Entropion

Piroxicam photodermatitis

Epidermolysis bullosa, recessive dystrophic – symblepharon Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 135–151; EB, plakophilin deficiency – blepharitis JAAD 58:931–950, 2008; EBS with muscular dystrophy – ptosis JAAD 58:931–950, 2008

Polymorphic light eruption

Erythroderma – ectropion

Quinidine photo-lichen planus

358 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Granuloma annulare Ped Derm 16:373–376, 1999; Ann Ophthalmol 17:73–75, 1985

Seborrheic blepharitis The Clinical Management of Itching; Parthenon; p. 35, 2000;

Granuloma faciale – red eyelid plaque JAAD 53:1002–1009, 2005; AD 138:527–532, 2002

Terra firme – personal observation

Harlequin fetus (ichthyosis congenital fetalis) – autosomal recessive; ectropion; rigid plates; severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis; ABCA 12 (adenosine triphosphate binding cassette A12); keratinocyte lipid transfer associated with lamellar granule formation and lipid transfer via lamellar granules on the surface of keratinocytes AD 142:914–918, 2006; BJD 153:811–814, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982 Ichthyosiform erythroderma – ectropion Ichthyosis – ectropion JAMA Derm 149:598–600, 2013 Ichthyosis en confetti – ectropion JAMA Derm 151:64–69, 2015 Keratosis follicularis spinulosa decalvans – blepharitis JAAD 47:S275–278, 2002 Keratosis lichenoides chronica (Nekam’s disease) – reticulated flat-­topped keratotic papules, linear arrays, atrophy, comedo-like lesions, prominent telangiectasia; conjunctival injection, scarring eye lesions including blepharitis, conjunctivitis, iridocyclitis, keratoconjunctivitis, anterior uveitis; seborrheic dermatitis-like eruption; acral dermatitis over toes; punctate keratotic papules of palmar creases; scaly red papules of face; seborrheic dermatitis-like rash of face; nail dystrophy; oral and genital erosions, conjunctivitis AD 147:1317–1322, 2011; Cutis 86:245–248, 2010; Ped Derm 26:615–616, 2009; AD 145:867–69, 2009; AD 144:405–410, 2008; Am J Dermatopathol 28:260–275, 2006; JAAD 49:511–513, 2003; Dermatology 201:261–264, 2000; JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; Dermatopathol Pract Concept 3:310–312 1997; AD 131:609–614, 1995; Dermatology 191:188–192, 1995; AD 105:739–743, 1972; Presse Med 51:1000–1003, 1938; Arch Dermatol Syph (Berlin) 31:1–32, 1895; in children JAAD 56:S1–5, 2007 Kimura’s disease Surv Ophthalmol 44:79–91, 1999; Br J Ophthalmol 76:755–757, 1992 Lamellar ichthyosis - ectropion Ped Derm 34:584–589, 2017; JAMA Derm 153:476–477, 2017 Laxity of the eyelid Dermatol Clin 10:793–798, 1992 Lichen planus Dermatol Online J 7:5, 2001; Dermatology 191:350– 351, 1995; JAAD 27:638–639, 1992 Lichen sclerosus et atrophicus Dermatol Online J Oct 16, 2013; Can J Ophthalmol 3:39–42, 1968 Lichen simplex chronicus Arch Ophthalmol 117:829–831, 1999 Non-bullous CIE (congenital ichthyosiform erythroderma) (erythrodermic lamellar ichthyosis) – autosomal recessive – presents with collodion baby; ectropion AD 121:477–488, 1985 Periorbital dermatitis (periorbital variant of perioral dermatitis) – idiopathic or topical corticosteroid-associated Rook p. 2110–2111, 1998, Sixth Edition; including facial Afro-Caribbean childhood eruption (FACE) BJD 91:435–438, 1976 Psoriasis – may mimic chronic blepharitis JAAD 65:1202–1212, 2011red eyelid plaque AD 138:527–532, 2002 Ptosis – congenital, aging, Horner’s syndrome, third nerve palsy, myasthenia gravis, myotonic dystrophy, Ehlers-Danlos syndrome; Frydman syndrome (ptosis with blepharophimosis, epicanthus inversus and telecanthus) Sebopsoriasis in HIV disease BJD 176:813–815, 2017

Vitiligo, including segmental vitiligo – personal observation

PSYCHOCUTANEOUS DISEASE Factitial dermatitis Br J Ophthalmol 82:97, 1998

SYNDROMES Aarskog syndrome – ptosis Birth Defects 11:25–29, 1975 Ablepharon macrostomia syndrome – absent eyelids, ectropion, abnormal ears, hypertelorism, aplasia or rudimentary nipples, dry, lax, redundant skin, macrostomia, ambiguous genitalia Hum Genet 97:532–536, 1996; Am J Med Genet 31:299–304, 1988 Ablepharon with follicular ichthyosis and hairy pinnae Clin Genet 2:111–114, 1971 Acrocallosal syndrome (Greig cephalopolysyndactyly syndrome) – abnormal upper lids, frontonasal dysostosis, callosal agenesis, cleft lip/palate, redundant skin of neck, grooved chin, bifid thumbs, polydactyly, syndactyly Am J Med Genet 43:938–941, 1992 Acrocraniofacial dysostosis – ptosis Am J Med Genet 29:95–106, 1988 Acrofacial dysostosis (Reynolds syndrome) – ptosis Am J Med Genet Suppl 2:143–150, 1986 AEC syndrome (Hay-Wells syndrome) – ankyloblepharon, ectodermal dysplasia, cleft lip/palate syndrome – blepharitis, eyelid papillomas, periorbital wrinkling; microcephaly, widespread congenital scalp erosions; alopecic ulcerated plaques of scalp, trunk, groin; alopecia of scalp and eyebrows; congenital erythroderma; depigmented patches; syndactyly; bony abnormalities; widely spaced nipples; TP63 mutation Ped Derm 28:15–19, 2011; Ped Derm 26:617–618, 2009; AD 141:1591–1594, 2005; AD 141:1567–1573, 2005; AD 134:1121–1124, 1998; Ped Derm 14:149–150, 1997; generalized fissured erosions of trunk BJD 149:395–399, 2003; TP63 mutations seen in AEC syndrome, EEC syndrome, Rapp-Hodgkin syndrome, limb-mammary syndrome, split-hand split-foot malformation type 4, acro-dermatoungual-lacrimal-tooth syndrome AD 141:1567–1573, 2005 Anhidrotic ectodermal dysplasia – folds and creases of upper and lower eyelids Ped Derm 23:396–398, 2005; J Med Genet 38:579– 585, 2001; Am J Med Genet 53:153–162, 1994 Ankyloblepharon – AEC (Hay-Wells) syndrome, ADULT syndrome, EEC syndrome, Limb-mammary syndrome JAAD 47:805, 2002 Ankyloblepharon with cleft palate Br J Ophthalmol 63:129, 1969 Arthrogryposis, renal tubular dysfunction, and cholestasis (ARC) syndrome – ichthyosis, scarring alopecia, ectropion, arthrogryposis of wrist, knee, and hip Ped Derm 22:539–542, 2005 Ascher's syndrome – blepharochalasis with progressive enlargement of upper lip; increased thickness of eyelids AD 139:1075– 1080, 2003; JAAD 29:650–651, 1993; Ped Derm 8:122–123, 1991; BJD 66:129–138, 1954; Klin Monatsbl Augenheilkd 65:86–97, 1920; recurrent eyelid edema and ptosis AD 145:498–499, 2009 Ataxia telangiectasia – telangiectasias of eyelids, bulbar conjunctivae, tip of nose, ears, antecubital and popliteal fossae, dorsal hands and feet; atrophy with mottled hypo- and hyperpigmentation, dermatomal CALMs, photosensitivity, canities, acanthosis nigricans, dermatitis; cutaneous granulomas present as papules or nodules,

Eyelid Lesions red plaques with atrophy or ulceration JAAD 10:431–438, 1984; Ann Int Med 99:367–379, 1983 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ablepharon, ectropion of lower eyelids, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Am J Med Genet 47:20–23, 1993; Syndrome Ident 8:6–9, 1982 Basaloid follicular hamartoma syndrome – multiple skin-colored, red, and hyperpigmented papules of the face, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes) JAAD 43:189–206, 2000 Beckwith-Wiedemann syndrome (Exomphalos-MacroglossiaGigantism) (EMG) syndrome – autosomal dominant; zosteriform rash at birth, exomphalos, macroglossia, visceromegaly, facial salmon patch of forehead, upper eyelids, nose, and upper lip and gigantism; linear earlobe grooves, circular depressions of helices; increased risk of Wilms’ tumor, adrenal carcinoma, hepatoblastoma, and rhabdomyosarcoma JAAD 37:523–549, 1997; Am J Dis Child 122:515–519, 1971 Behcet’s disease – unilateral ptosis, headache, neuro-Behcet’s Arch Rheum 18:221–224, 2017 Benign joint hypermobility syndrome – arthralgia, joint dislocation, hyperextensible skin, laxity of eyelids, normal skin texture and thickness (unlike Ehlers-Danlos syndrome) J Rheumatol 13:239– 243, 1986 Blepharophimosis syndrome – autosomal dominant; ptosis, blepharophimosis, epicanthus inversus, telecanthus Am J Ophthalmol 72:625–631, 1971 Bloom's syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; slender face, prominent nose; facial telangiectatic erythema with involvement of eyelids, ear, and hand and forearms; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy, no neurologic deficits Am J Hum Genet 21:196– 227, 1969; AD 94:687–694, 1966 Borjeson-Forssman-Lehman syndrome – ptosis Am J Med Genet 19:653–664, 1984 Bowen-Armstrong syndrome (cleft lip-palate, ectodermal dysplasia, mental retardation) – ankyloblepharon Clin Genet 9:35–42, 1976 Branchiooculofacial syndrome – autosomal dominant; microphthalmia, coloboma, congenital bilateral cervical ulcerations (bilateral ectopic thymus glands); congenital ulcerated neck mass (ectopic thymus), flattened nasal tip, pseudo-cleft lip, posterior rotated ears, pre-auricular pit, cleft lip, nasolacrimal duct stenosis or atresia, dolichocephaly; mutation in TFAP2A (retinoic acid responsive gene) Ped Derm 29:759–761, 2012; Mol Vis 16:813–818, 2010; Arch Otolaryngol Head Neck Surg 128:714–717, 2002; pseudocleft of upper lip, cleft-lip-palate, and hemangiomatous branchial cleft – atrophic neck lesions Ped Derm 29:383–384, 2012; Am J Med Genet 27:943–951, 1987 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – fever, recurrent annular violaceous plaques and nodules, violaceous eyelid edema, low weight and height, lipodystrophy, hepatosplenomegaly, and inflammation Ped Derm 26:654, 2009

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Cardio-facio-cutaneous syndrome (NS) – ptosis, xerosis/ichthyosis, eczematous dermatitis, alopecia, growth failure, hyperkeratotic papules, ulerythema ophryogenes (decreased or absent eyebrows), seborrheic dermatitis, CALMs, nevi, keratosis pilaris, autosomal dominant, patchy or widespread ichthyosiform eruption, sparse scalp hair and eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990 Carnevale syndrome – ptosis Am J Med Genet 33:186–189, 1989 Carney complex (NAME/LAMB) – myxoma JAAD 43:377–379, 2000; bilateral Br J Ophthalmol 75:251–252, 1991 Char syndrome (short philtrum, patulous lips, ptosis, low-set pinnae) Birth Defects 14(6B):303–305, 1978 Congenital ichthyosis, alopecia, eclabion, ectropion, mental retardation – autosomal recessive Clin Genet 31:102–108, 1987 Congenital plasminogen deficiency – autosomal recessive; chronic mucosal pseudomembranous lesions with white membranes of gingivae, and eyelids; blepharitis, gingival hyperplasia, leukoplakia, ligneous conjunctivitis; thick nodular eyelids Ped Derm 448–451, 2009 Cowden's disease – trichilemmomas (small pebbly papules) JAAD 11:1127–1141, 1984 Craniocarpotarsal dysplasia (whistling face syndrome) – ptosis J Med Genet 14:139–141, 1977 CRIE syndrome – congenital reticulated ichthyosiform erythroderma – formerly ichthyosis en confetti (includes ichthyosis variegate, MAUIE syndrome); minor criteria include collodion membrane, nail dystrophy, large lunulae, palmoplantar hyperkeratosis, ectropion, strabismus, nystagmus, joint contractures, small weight and length; decreased finger length, decreased eyebrows and eyelashes JAMA Derm 151:64–69, 2015; JAMA Derm 151:15–16, 2015; Acta DV 94:579–582, 2014; Dermatology 188:40–45, 1994 Cryptophthalmos syndrome (Fraser syndrome) Am J Med Genet 31:159–168, 1988 Curly hair-ankyloblepharon-nail dysplasia syndrome – abnormal dentition (form of hypophidrotic ectodermal dysplasia) Birth Defects Orig Art Ser 7:100–102, 1971 Cutaneous segmental heterotopic meningeal tissue with multifocal neural and mesenchymal hamartomas – skin colored pedunculated papules of forehead, eyelids, scalp, ala nasi; hypertrichotic heterotopic meningeal nodule BJD 156:1047–1050, 2007 Del (13q) syndrome – ptosis Eur J Pediatr 128:27–31, 1978 Deletion of short of chromosome 18 – mental and growth deficiency, microcephaly, ptosis Am J Med Genet 66:378–398, 1996 Delleman-Oorthuys syndrome – oculocerebrocutaneous syndrome – eyelid tag, periorbital tags, facial tags, orbital cysts, focal punched-out skin defects of the ala nasi, cerebral malformations Clin Dysmorphol 7:279–283, 1998 Didymosis aplasticosebacea – aplasia cutis congenita in a nevus sebaceus (Schimmelpenning syndrome); coloboma of eyelid Ped 24:514–516, 2007 Digitocutaneous dysplasia – X-linked dominant; digital fibromas, atrophic plaques with appearance of hyperpigmentation, metacarpal and metatarsal disorganization with resultant brachydactyly and clinodactyly, dysmorphic features including frontal bossing, broad nasal root, telecanthus and epicanthal folds, ptosis of the eyelids, conical teeth, dental fissures, hypodontia, accessory gingival frenula, enamel hypoplasia JAAD 56:S6–9, 2007

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Down’s syndrome – thickened eyelids and syringomas AD 77:319– 323, 1958; milia-like syringomas with calcification – white eyelid papules BJD 157:612–614, 2007 Dubowitz syndrome – ptosis; narrow eyelids Eur J Pediatr 144:574– 578, 1986 Dup (10q) syndrome – ptosis Hum Genet 46:29–40, 1979 Ectodermal dysplasia – ankyloblepharon, absent lower eyelashes, hypoplasia of upper lids, coloboma, seborrheic dermatitis, cribriform scrotal atrophy, ectropion, lacrimal duct hypoplasia, malaligned great toenails, gastroesophageal reflux, ear infections, laryngeal cleft, dental anomalies, scalp hair coarse and curly, sparse eyebrows, xerosis, hypohidrosis, short nose absent philtrum, flat upper lip BJD 152:365–367, 2005 Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome (EEC syndrome) – chronic blepharitis Ped Derm 20:113–118, 2003 Encephalocranial lipomatosis (Haberland syndrome) – lipomatous hamartomas of scalp and eyelids; linear yellow papules of forehead extending to eyelids; ophthalmologic manifestations; seizures, mental retardation; mandibular or maxillary ossifying fibromas and odontomas; cranial asymmetry; developmental delay, mental retardation, seizures, spasms of contralateral limbs; unilateral porocephalic cysts with cortical atrophy Ped Derm 35:825–826, 2018; Ped Derm 23:27–30, 2006; Ped Derm 22:206–209, 2005; JAAD 47:S196–200, 2002; Am J Med Genet 191:261–266, 2000; JAAD 37:102–104, 1998; BJD 104:89–96, 1981; Arch Neurol 22:144–155, 1970 Epidermal nevus syndrome – pedunculated eyelid papules JAAD 50:957–961, 2004 Eyelid cysts, hypodontia and hypotrichosis JAAD 10:922–925, 1984 Familial dyskeratotic comedones Fetal alcohol syndrome – narrow eyelids Drug Alcohol Depend 14:1–10, 1984 FG syndrome (unusual facies, mental retardation, congenital hypotonia, imperforate anus) – short narrow eyelids Am J Med Genet 19:383–386, 1984 Floppy eyelid syndrome – eversion of lids during sleep BJD 151:706, 2004 Frydman syndrome – autosomal recessive; prognathism, syndactyly, short stature, blepharophimosis, weakness of extraocular and frontal muscles, synophrys Clin Genet 41:57–61, 1992 Geroderma osteodysplastica (Bamatter syndrome) (osteodysplastic geroderma) – autosomal recessive; short stature, cutis laxa-like changes with drooping eyelids and jowls (characteristic facies), osteoporosis and skeletal abnormalities; lax wrinkled, atrophic skin and joints, growth retardation Ped Derm 23:467–472, 2006; Am J Med Genet 3:389–395, 1979; Hum Genet 40:311–324, 1978 Goldenhar syndrome - mandibulofacial dysostosis Hereditary angioneurotic edema (Quincke's edema) – autosomal dominant; prodrome of erythema marginatum (annular urticarial eruption); facial, lip, eyelid, tongue, and hand edema JAAD 65:843–850, 2011; Monatsh Prakt Derm 1:129–131, 1882; Edinb Med J 22:513–526, 1876 Hereditary gelsolin amyloidosis (AGel amyloidosis) – cutis laxa with blepharochalasis, corneal lattice dystrophy, cranial and peripheral polyneuropathy BJD 152:250–257, 2005 Juvenile hyaline fibromatosis – eyelid nodules JAAD 61:695–700, 2009; Br J Plast Surg 58:106–111, 2005 Kabuki syndrome (Kabuki makeup syndrome) (Niikawa-Kuroki syndrome) – short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lateral lower eyelids, sparse arched lateral eyebrows,

epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips (thick everted lower lip), high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix and hypoplastic antihelices, lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly; preauricular dimple/fistula; sparse hair, hypoplastic nails, café au lait macules, hypodontia, hyper- and hypopigmentation, aplasia cutis congenital, conical and screwdriver teeth, joint laxity Ped Derm 28:507–511, 2011; Ped Derm 24:309– 312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260– 262, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 570–573, 1981 Keratosis-ichthyosis-deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990; JAAD 23:385–388, 1990; JAAD 19:1124–1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915; fissured lips – paronychial pustules, blepharitis without keratitis, perineal psoriasiform plaques, tongue erosions, honeycomb palmoplantar keratoderma; red gingivae Kindler's syndrome – ectropion; acral bullae in infancy; progressive poikiloderma with photosensitivity; nail dystrophy, webbing of digits, esophageal and urethral stenosis, poor dentition, gingival fragility, aged hands with fine wrinkling and scarring, hyperkeratosis of hands and palms and soles, dyspigmentation, diffuse telangiectasias, hypshort arm chromosome 20; Kind 1; actin cytoskeletonextracellular matrix interactions (membrane associated structural and signaling protein BJD 160:1119–1122, 2009; AD 142:1619– 1624, 2006; AD 142:620–624, 2006; BJD 66:104–111, 1954 Laryngo-onycho-cutaneous syndrome (Shabbir syndrome) – autosomal recessive; symblepharon, crusted erosions of elbows, anonychia with granulation tissue of nail bed,, mucosal nodule of hard palate; hoarse cry and laryngeal stenosis, chronic granulation tissue, conjunctival inflammation with polypoid granulation tissue, tooth enamel hypoplasia; laminin alpha 3A mutation (LAMA 3A) with N–terminal deletion of LAMA 3A Ped Derm 24:306–308, 2007; Ped Derm 23:75–77, 2006; Cornea 20:753–756, 2001; Arch Dis Child 70:319–326, 1994; JAAD 29:906–909, 1993; Clin Dysmorphol 1:3–14, 1992; Eye 5:717–722, 1991; Biomedica 2:15–25, 1986 Leprechaunism (Donohue’s syndrome) – ptosis, decreased subcutaneous tissue and muscle mass, characteristic facies, severe intrauterine growth retardation, broad nose, low set ears, hypertrichosis of forehead and cheeks, loose folded skin at flexures, gyrate folds of skin of hands and feet; breasts, penis, clitoris hypertrophic Endocrinologie 26:205–209, 1988 Lipoid granulomatosis (Erdheim-Chester disease) – yellow eyelid papules Lipoid proteinosis – papules along the lash margin; mutation in ECM 1 (decreased ECM 1 protein) JAMA Derm 155:977–979, 2019; AD 144:1383–1388, 2008; Int J Derm 39:203–204, 2000; Acta Paediatr

Eyelid Lesions 85:1003–1005, 1996; JAAD 27:293–297, 1992; Virchows Arch Pathol Anat 273:285–319, 1929 Lymphedema-distichiasis syndrome – periorbital edema, vertebral abnormalities, spinal arachnoid cysts, congenital heart disease, thoracic duct abnormalities, hemangiomas, cleft palate, microphthalmia, strabismus, ptosis, short stature, webbed neck Ped Derm 19:139–141, 2002 Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high pitched voice; mutation in RIN2 JAAD 66:842–851, 2012 Marcus Gunn phenomenon (winking jaw syndromes) – ptosis Am J Ophthalmol 82:503–504, 1976 MAUIE syndrome – micropinnae, alopecia, ichthyosis, and ectropion JAAD 37:1000–1002, 1997 Melkersson-Rosenthal syndrome – granulomatous blepharitis; chronic eyelid swelling Diagn Pathol Nov 13, 2013; Ophthalmology 104:1185–1189, 1997 MEN IIB – eyelid thickening, submucosal neuromas Orbit 38:514– 518, 2019

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Nevoid basal cell carcinoma (Gorlin’s) syndrome – Meibomian gland cysts of eyelids BJD 164:245–256, 2011; JAAD 11:98–104, 1984; AD 114:95–97, 1978; Birth Defects 8:140–148, 1971 Nevus sebaceus syndrome (Schimmelpenning-Feuerstein-Mims syndrome) – ectropion, hamartomas of eyelid, ptosis J Coll Physicians and Surg Pak 25:220–222, 2015; JAAD 61:563–571, 2009; Dermatologica 181:221–223, 1990; Fortschr Geb Rontgenstr Nuklearmed 87:716–720, 1957 Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, prenatal onset short stature, growth retardation, bird-like facies with epicanthal folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of face, café au lait macules, vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair 3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000; Am J Med Genet 66:378–398, 1996 Noonan syndrome – ptosis J Med Genet 24:9–13, 1987

MEN type III – eyelid papules – plexiform neuromas JAAD 36:296–300, 1997

Oculo-auricular vertebral syndrome – epibulbar dermoid tumors Ped Derm 20:182–184, 2003

Mitochondrial dystrophy – personal observation

Oculocerebral hypopigmentation syndrome of Preus – very short with thin build, ptosis, high arched palate, dental malocclusion, prominent central upper incisors, hair and skin hypopigmented, deafness, severe mental retardation Ped Derm 24:313–315, 2007

Moebius syndrome – ptosis J Med Genet 14:415–417, 1977 Muir-Torre syndrome – sebaceous neoplasms AD 142:1039–1042, 2006 Multicentric reticulohistiocytosis – multiple papules Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 149 Multiple basaloid follicular hamartoma syndrome – personal observation Multiple mucosal neuroma syndrome (MEN IIB) (Gorlin’s syndrome) (Wagenmann-Froboese syndrome) – autosomal dominant; skin-colored papules of cheeks and nodules of lips, tongue, oral mucosa (buccal mucosa, gingiva, palate, pharynx); medullary carcinoma of the thyroid; adrenal medulla pheochromocytoma; eversion of lips and eyelids, widened nasal base; marfanoid features; RET proto-oncogene NEJM 364:870, 2011; JAAD 55:341–344, 2006; Curr Prob Derm 14:41–70, 2002; Am J Med 31:163–166, 1961; thickened eyelid margins AD 139:1647–1652, 2003; JAAD 42:939–969, 2000 Multiple pterygium syndrome – ptosis Am J Med Genet 7:91–102, 1980 Myotonic dystrophy (Steinert syndrome) – ptosis J Pediatr 81:83– 86, 1972 Neu-Laxova syndrome – rudimentary eyelids, polyhydramnios, growth retardation, microcephaly, ichthyosis, thick hyperkeratotic skin Am J Med Genet 43:602–605, 1992 Neurofibromatosis type I – plexiform neurofibroma of the eyelids J Maxillofac Surg 12:78–85, 1984 Neutral lipid storage disease (Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma; thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness BJD 144:430–432, 2001; JAAD 17:801–808, 1987; AD 121:1000–1008, 1985

Olmsted syndrome – personal observation Pallister-Killian syndrome – ptosis J Clin Dysmorphol 1:2–3, 1983 Penchaszadeh syndrome (nasopalpebral lipoma-coloboma syndrome) – eyelid lipoma Am J Med Genet 11:397–410, 1982 Phakomatosis pigmentokeratotica – ptosis; coexistence of an organoid nevus and a checkerboard papular speckled lentiginous nevus; organoid nevus associated with hypophosphatemic vitamin D-resistant rickets JAAD 55:S16–20, 2006; Eur J Dermatol 10:190–194, 2000; Ped Derm 15:321–323, 1998; AD 134:333–337, 1998 Popliteal pterygium syndrome – autosomal dominant; eyelid adhesions, bilateral popliteal pterygia, intercrural pterygium, hypoplastic digits, valgus or varus foot deformities, syndactyly, cryptorchidism, inguinal hernia, cleft scrotum, lower lip pits, mucous membrane bands J Med Genet 36:888–892, 1999; Int J Pediatr Otorhinolaryngol 15:17–22, 1988 Prader-Willi syndrome – albinoid skin; almond-shaped eyes, narrow bifrontal diameter, thin upper lip, short stature, central obesity, small hands and feet, mental retardation, hypogonadism, hypotonia at birth, excoriations, trichotillomania Cutis 90;129–131, 2012; Growth Genet Hormones 2:1–5, 1986; Schweiz Med Wschr 86:1260–1261, 1956 Ptosis-aortic coarctation syndrome J Pediatr Surg 22:724–726, 1987 Ptosis and unusual facies Am J Med Genet 7:5–9, 1980 Rapp-Hodgkin hypohidrotic ectodermal dysplasia – autosomal dominant; alopecia of wide area of scalp in frontal to crown area, short eyebrows and eyelashes, coarse wiry sparse hypopigmented scalp hair, sparse body hair, scalp dermatitis, ankyloblepharon, syndactyly, nipple anomalies, cleft lip and/or palate; nails narrow and dystrophic, small stature, hypospadias, conical teeth and anodontia or hypodontia; distinctive facies, short stature JAAD 53:729–735, 2005; Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968

362 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Restrictive dermopathy – autosomal recessive, swollen eyelids, erythroderma at birth, with extensive erosions and contractures; taut shiny skin; fetal akinesia, multiple joint contractures, dysmorphic facies with fixed open mouth, hypertelorism, pulmonary hypoplasia, bone deformities; uniformly fatal Ped Derm 19:67–72, 2002; Ped Derm 16:151–153, 1999; AD 134:577–579, 1998; AD 128:228–231, 1992

arteriovenous malformation of the brain Am J Ophthalmol 75:224– 291, 1973

Robinow syndrome (fetal face syndrome) – ankyloblepharon Clin Genet 31:77–85, 1987

TRAUMA

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – eyelid edema, periorbital edema BJD 145:323–326, 2001; Trans Am Ophthalmol Soc 86:113–135, 1988; bilateral eyelid edema Ped Derm 17:377–380, 2000; Ophthal Plast Reconstr Surg 15:52–55, 1999

Scars – ectropion

Xeroderma pigmentosum – blepharospasm, entropion, ectropion, symblepharon, scarring and tumors of eyelids JAAD 75:855–870, 2016

Eyelid laceration – in neonate by fetal monitoring electrode Am J Ophthalmol 125:715–717, 1998

Saethre-Chotzen syndrome – ptosis J Pediatr 76:928–930, 1970

VASCULAR DISEASES

Schopf-Schulz-Passarge syndrome – hidrocystomas (cysts on eyelid margins), conical teeth, alopecia (thin scalp hair), fissured reticulated palmoplantar keratoderma, decreased number of teeth, brittle and furrowed nails BJD 171:1211–1214, 2014; Ped Derm 30:491–492, 2013; JAAD 65:1066–1069, 2011; Acta DV 88:607– 612, 2008; AD 140:231–236, 2004; JAAD 36:569–576, 1997; BJD 127:33–35, 1992; Birth Defects XII:219–221, 1971

Angiofibromas – papule

Schwartz-Jampel syndrome (chondrodystrophic myotonia) – ptosis, hypertrichosis of the eyelids Arch Ophthalmol 68:52–57, 1962

Blue rubber bleb nevus syndrome – personal observation

Shabbir syndrome – ulcerative lesions of cheeks and ears, dystrophic nails Nepal J Ophthalmol 11:105–107, 2019 Sjogren’s syndrome – eyelid pruritus and dermatitis Int J Derm 33:421–424, 1994 Smith-Lemli-Opitz syndrome – ptosis Am J Med Genet 28:733–734, 1987; Clin Pediatr 16:665–668, 1977 Sturge-Weber syndrome (encephalofacial angiomatosis) – facial port wine stain almost invariably involving upper eyelid with homolateral leptomeningeal angiomatosis Pediatrics 76:48–51, 1985 Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – hyperpigmented eyelids, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997 Tuberous sclerosis – angiofibromas of eyelids BJ Ophtalmol 85:420–423, 2001; J Pediatr Ophthalmol 13:156–158, 1976; white eyelashes South Med J 75:227–228, 1982 Turner syndrome – ptosis J Craniofac Genet Dev Biol 5:327–340, 1985 Van der Woude syndrome – ankyloblepharon, congenital sinuses of the lower lip Am J Hum Genet 19:416–432, 1967 Velocardiofacial syndrome – short narrow eyelids J Craniofac Genet Dev Biol 4:39–46, 1984 Vogt-Koyanagi-Harada syndrome – depigmented eyelids JAAD 15:17–24, 1986 Wells’ syndrome AD 142:1157–1161, 2006 Williams syndrome – premature laxity of skin, congenital heart disease (supravalvular aortic stenosis), baggy eyes, full cheeks, prominent lips, dental malocclusion, delayed motor skills, cocktail party personality J Pediatr 113:318–326, 1988 Wyburn-Mason (Bonnet-Dechaume-Blanc) syndrome – unilateral salmon patch with punctate telangiectasias or port wine stain; unilateral retinal arteriovenous malformation, ipsilateral aneurysmal

Arteriovenous hemangioma (cirsoid aneurysm or acral arteriovenous tumor) – associated with chronic liver disease BJD 144:604– 609, 2001 Arteriovenous malformation Ophthalmic Surg 26:145–152, 1995; Ophthalmic Surg 11:771–777, 1980 Capillary malformation (port wine stain, salmon patch, angel’s kiss, stork bite, nevus simplex, vascular stain) JAAD 56:353–370, 2007 Capillary malformation-AVM syndrome – red patch of eyelid with white halo Ped Derm 37:64–68, 2020 Carotid-cavernous sinus fistula – eyelid edema JAAD 48:617–619, 2003 Cherry angioma – papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.113 Congestive heart failure – eyelid edema JAAD 48:617–619, 2003 Disseminated neonatal angiomatosis Ped Derm 7:63–66, 1990 Dural arteriovenous malformation – eyelid edema JAAD 48:617– 619, 2003 Eosinophilic granulomatosis with polyangiitis – proptosis, orbital myositis Ophthalmic Plastic Reconstr Surg 35:7–16, 2019 Glomus tumor – painless non-tender violaceous nodule Jap J Ophthalmol 48:418–426, 2004; solitary and sporadic or multiple familial Ophthalmol 100:139–143, 1993; papule Ophthalmology 100:139–143, 1993 Granulomatosis with polyangiitis – necrotizing inflammation of eyelid NEJM 352:392, 2005; yellow eyelid papules (florid xanthelasmata) Br J Ophthalmol 79:453–456, 1995; unilateral eyelid edema Caspian J Intern Med 10:343–346, 2019 Hemangioma, infantile BJD 169:125–129, 2013;- eyelid swelling BJD 162:466–468, 2010; periocular hemangioma – red facial plaque JAAD 55:614–619, 2006; Am J Ophthalmol 124:403–404, 1997; Dermatol Clin 10:653–661, 1992; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, pp.109–111; focal hemangioma AD 139:869– 875, 2003; conjunctival infantile hemangioma Ped Derm 34:681– 685, 2017 Hemangiopericytoma Am J Ophthalmol 121:445–447, 1996 Henoch-Schonlein purpura – eyelid and facial edema due to intracerebral hemorrhage Brain and Development 24:115–117, 2002; upper eyelid ecchymoses and edema Arch Ophthalmol 117:842–843, 1999 Lymphangioma Ophthalmology 91:1278–1284, 1984; lymphangioma circumscriptum BJ Ophthalmol 74:574–575, 1990; papule

Eyes, Red and Rash 363 Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 119 Masson tumor of the eyelid – intravascular papillary endothelial hyperplasia J Craniofac Surg 25:1529–1530, 2014 PHACES syndrome – large facial hemangioma; Dandy-Walker malformation (posterior fossa cyst with hypoplasia of the cerebellar vermis; cystic dilatation of the fourth ventricle leading to hydrocephalus and increased head circumference) Ped Derm 26:730–734, 2009; Neuroradiology 16:82–84, 1978 Port wine stain Pyogenic granuloma NEJM 376:1667, 2017; J Am Optok Assoc 58:664–673, 1987 Salmon patch (nevus simplex) (“stork bite”) – pink macules with fine telangiectasias of the nape of the neck, glabella, forehead upper eyelids, tip of nose, upper lip, midline lumbosacral area Ped Derm 6:185–187, 1989; Ped Derm 73:31–33, 1983

Cicatricial pemphigoid (mucous membrane pemphigoid) JAMA Derm 151:646–650, 2015; AD 138:370–379, 2002; JAAD 43:571– 591, 2000; J Periodontol 71:1620–1629, 2000; Cutis 63:181–183, 1999; JAAD 24:987–1001, 1991; BJD 118:7–10, 1988; ocular cicatricial pemphigoid AD 129:456–459, 1993; anti-laminin 332 (anti-epiligrin) cicatricial pemphigoid BJD 165:815–822, 2011;blister on bulbar conjunctivum BJD 162:898–899, 2010; JAAD 42:841– 844, 2000; anti-laminin gamma 1 and anti-laminin 332 mucous membrane pemphigoid – lip erosions, nasal erosions, conjunctival erosions, scrotal ulcers BJD 171:1257–1259, 2014 Common variable immunodeficiency BJD 144:597–600, 2001 Connective tissue disease – retiform purpura JAAD 82:783–796, 2020 Dermatitis herpetiformis Dermatomyositis Epidermolysis bullosa acquisita AD 135:954–959, 1999;

Sinus pericranii JAAD 46:934–941, 2002

JAAD 16:439–443, 1986

Thrombosed varix - papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.119

Gain of function mutation of NLRC4 (inflammasome) – fever, periodic urticarial rash, conjunctivitis, arthralgias, painful red nodules of foot or leg, enterocolitis, splenomegaly, macrophage activation syndrome; increased IL-18 BJD 176:244–248, 2017; Nat Genet 46:1135–1139, 2014; Nat Genet 46:1140–1146, 2014; J Exp Med 211:2385–2396, 2014

EYES, RED AND RASH  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic conjunctivitis JAMA 310:1721–1729, 2013 Allergic contact dermatitis – latex J Occup Environ Med 42:613– 621, 2000; flowers Contact Dermatitis 42:369–370, 2000; tulip workers Cutis 71:319–321, 2003; JAAD 7:500–503, 2003; eye drops (phenylephrine) J Invest Allergol Clin Immunol 9:55–57, 1999; food (potato, onion) – facial dermatitis, contact urticaria, rhinoconjunctivitis Am J Contact Dermat 10:40–42, 1999; methacrylate Allergy 51:56–59, 1996; epoxy resins Dermatitis 25:34, 2014 Anti-laminin 332 mucous membrane pemphigoid – conjunctivitis with symblepharon; desquamative gingivitis BJD 169:100–105, 2013 Antiphospholipid antibody syndrome – uveitis and central nervous system disease NEJM 380:1062–1071, 2019 APLAID (autoinflammation and PLAID) – sinopulmonary infections, interstitial pneumonitis, eye inflammation, colitis, arthralgias; epidermolysis bullosa-like eruptions in infancy with vesiculopustular lesions and red plaques JAAD 73:367–381, 2015 Atopic keratoconjunctivitis – red eye and blindness JAAD 70:569– 575, 2014 Autoimmune iritis and alopecia areata – personal observation Benign familial neutropenia – conjunctivitis and blepharitis JAAD 30:877–880, 1994 Bullous pemphigoid – anti-p200 bullous pemphigoid – conjunctival erosions BJD 160:462–464, 2009 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis, epididymitis, coldinduced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, conjunctivitis Ped Derm 33:602–614, 2016 Chronic granulomatous disease JAAD 36:899–907, 1997

Graft vs. host disease, chronic – keratoconjunctivitis sicca JAAD 70:795–819, 2014; JAAD 38:369–392, 1998; AD 134:602–612, 1998 acute GVHD – corneal sloughing, pseudomembranous conjunctivitis; chronic GVHD – conjunctivitis, dry eye, cicatricial ectropion, symblepharon JAAD 70:795–819, 2014 H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; mutation in SLC29A3 gene (equilabrative nucleoside transporter) Ped Derm 33:602–614, 2016 Hay fever conjunctivitis – associated with atopic dermatitis Juvenile rheumatoid arthritis (Still’s disease) Linear IgA disease – dry eye, burning, foreign body sensation JAAD 70:795–819, 2014; conjunctivitis JAAD 51:S112–117, 2004; JAAD 30:355–357, 1994; Ophthalmology 107:1524–1528, 2000; JAAD 19:792–805, 1988; cicatricial conjunctivitis AD 142:786–787, 2006; Ophthalmol 95:340–343, 1988; linear IgA disease vs. 290 Kd – cicatricial pemphigoid-like syndrome JAAD 31:884–888, 1994; JAAD 20:761–770, 1989; mimicking Stevens-Johnson syndrome BJD 178:786–789, 2018 Lupus erythematosus – systemic lupus erythematosus episcleritis BJD 135:355–362, 1996; scleritis NEJM 382:1750–1758, 2020; dry eye JAAD 70:795–819, 2014; uveitis and central nervous system disease NEJM 380:1062–1071, 2019; subacute cutaneous LE and keratoconjunctivitis sicca AD 128:1265–1270, 1992; discoid lupus with punctate keratopathy or stromal keratitis Arch Ophthalmol 107:545–547, 1989; conjunctival erythema; nodular episcleritis; lupus vasculitis – personal observation Mixed connective tissue disease – keratoconjunctivitis sicca, conjunctivitis, episcleritis, scleritis Eye and Skin Disease, pp.247– 251, Lippincott, 1996 Mucous membrane pemphigoid – conjunctivitis with corneal ulcers JAAD 70:795–819, 2014

364

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Neonatal-onset multisystem inflammatory disease (NOMID) – uveitis and central nervous system disease NEJM 380:1062–1071, 2019 Ocular mucous membrane pemphigoid Ped Derm 36:984–985, 2019 Ocular pemphigus JAAD 53:585–590, 2005 Pemphigus – El-Bagre endemic pemphigus; facial scaling and crusting, conjunctival injection, eyelid erythema and edema, ectropion, meibomitis JAAD 62:437–447, 2010

EXOGENOUS AGENTS Agave americana (century plant) dermatitis – palpable purpuric agave dermatitis with contact conjunctivitis Cutis 72:188–190, 2003 Air bag chemical keratitis JAAD 46:S25–26, 2002 Cobalt – light blue; uveitis Lancet ii:27–28, 1969 Foreign body conjunctivitis

Pemphigus foliaceus – conjunctivitis of endemic pemphigus of El Bagre region of Colombia JAAD 49:599–608, 2003

Synthetic opioid MT-45 – painful intertrigo, folliculitis, dry eyes, hair depigmentation, hair loss, Mees’ lines, abnormal liver function tests BJD 176:1021–1027, 2017

Pemphigus vulgaris JAAD 70:795–819, 2014; Curr Prob in Derm VIII:41–96, 1996; BJD 123:615–620, 1990

Spurge irritant contact dermatitis; diterpene esters Contact Dermatitis 20:63–78, 2009

Pseudopemphigoid Ophthalmology 88:95–100, 1981

Tattoo-associated uveitis JAMA 321:699–700, 2019; Wien Klin Wochenschr 120:18, 2008; Am J Ophthalmol 111:515–516, 1991; Lancet 2(7610):27–28, 1969

Relapsing polychondritis – scleritis NEJM 382:1750–1758, 2020; NEJM 380:1062–1071, 2019 Rheumatoid arthritis – episcleritis, scleritis NEJM 382:1750–1758, 2020; NEJM 380:1062–1071, 2019; JAAD 46:161–183, 2002; Rook p. 3006, 1998, Sixth Edition; peripheral ulcerative keratitis associated with neutrophilic disorders JAAD 40:331–334, 1999

INFECTIONS AND/OR INFESTATIONS

Scleroderma – keratoconjunctivitis sicca JAAD 70:795–819, 2014; Br J Ophthalmol 53:388–392, 1969; CREST syndrome

Acanthamoeba keratitis NEJM 381:274, 2019

Serum sickness with vasculitis – personal observation Sjogren’s syndrome JAAD 70:795–819, 2014; A Clinician’s Pearls and Myths in Rheumatology pp.107–130; ed John Stone; Springer 2009

Abscess – staphylococcal obturator abscess with adjacent ischial osteomyelitis J Am Osteopath Assoc 91:807–812, 1991 Actinomycosis – keratitis, conjunctivitis, anterior uveitis Eye and Skin Disease, pp. 567–570, Lippincott, 1996 Adenovirus – keratoconjunctivitis JAMA 310:1721–1729, 2013; JAMA 310:1439, 2013 Adenoviral conjunctivitis with erythema multiforme

DRUG-INDUCED Acetretin – conjunctival granulation tissue; swollen upper and lower eyelids JAAD 58:S41–42, 2008 Azathioprine – neutrophilic dermatosis (azathioprine hypersensitivity syndrome) – palpebral conjunctival erythema, pink macules, pink or red plaques JAMA Derm 149:592–597, 2013 Cetuximab – meibomitis JAAD 72:361–362, 2015 Corticosteroids – periorbital dermatitis and conjunctivitis Eye 12:148–149, 1998 Drug hypersensitivity syndromes Drug-induced pemphigoid Intravenous 5-fluorouracil therapy Ipilimumab – uveitis, iridocyclitis JAAD 71:217–227, 2014 Gold Isotretinoin, oral (retinoid conjunctivitis) – blepharoconjunctivitis JAAD 70:795–819, 2014; JAAD 19:209–211, 1988 Methotrexate, high dose and leucovorin – conjunctivitis and bullae Minocycline – drug-induced Sweet's syndrome JAAD 27:801–804, 1992 Morbilliform drug eruption Nicorandil – conjunctival and corneal ulcers Br J Ophthalmol 96:463–464, 2012 Pilocarpine – ocular pseudopemphigoid AD 136:113–118, 2000 Prostacycline flush – personal observation Ranitidine (Zantac) Robaxin – erythema multiforme – personal observation Toxic epidermal necrolysis Vancomycin – linear IgA disease mimicking toxic epidermal necrolysis JAAD 48:S56–57, 2003

Adenoviral pharyngoconjunctival fever African tick-bite fever – Rickettsia africae – episcleritis AD 142:1365–1366, 2006; Clin Inf Dis 39:700–701, 741–742, 2004 AIDS – keratoconjunctivitis sicca; pink patches of keratitis Arch Ophthalmol 102:201–206, 1984; AIDS-associated Kawasaki-like syndromes Clin Inf Dis 32:1628–1634, 2001; recurrent Kawasaki’s disease-like syndrome Clin Inf Dis 105–111, 2003; uveitis and central nervous system disease NEJM 380:1062–1071, 2019 Amebiasis – acanthamebiasis in AIDS AD 131:1291–1296, 1995 Angular blepharitis secondary to Staphylococcus aureus or Moraxella Arenaviruses (hemorrhagic fevers) – Lassa fever (rats and mice) (West Africa), Junin virus (Argentine pampas), Machupo virus (Bolivian savannas), Guanarito virus (Venezuela), Sabia virus (Southeast Brazil), Whitewater virus (California, New Mexico), Sabia virus, Tacaribe virus complex (mice) – swelling of face and neck, oral hemorrhagic bullae, red eyes; conjunctival injection, flushing, petechial rash, edema, purpura, ecchymoses JAAD 65:1213–1218, 2011; JAAD 49:979–1000, 2003 Babesiosis NEJM 366:2397–2407, 2012 Bacterial conjunctivitis, acute – Staphylococcus aureus, Staphylococcus epidermidis, Haemophilus influenza, Streptococcus pneumonia, Streptococcus viridans, Moraxella spp. JAMA 310:1721–1729, 2013 Bacterial conjunctivitis, hyperacute – Neisseria gonorrhoeae JAMA 310:1721–1729, 2013 Bartonellosis (Bartonella bacilliformis) – conjunctival lesions Clin Inf Dis 33:772–779, 2001 Blister beetle periorbital dermatitis and keratoconjunctivitis Eye 12:883–885, 1998 Brucellosis Cache Valley virus NEJM 336:547, 1997

Eyes, Red and Rash 365 Candidiasis, including chronic mucocutaneous candidiasis – keratoconjunctivitis; keratitis Clin Genet 27:535–542, 1985

Dermatophytosis

Cat scratch disease (Bartonella henselae) – Parinaud's oculoglandular syndrome – granulomatous conjunctivitis with pre-auricular adenopathy JAAD 70:795–819, 2014; Ped Derm 5:1–9, 1988; endogenous endophthalmitis Clin Inf Dis 33:718–721, 2001

Dirofilariasis, subcutaneous (migratory nodules) – eyelid, scrotum, breast, arm, leg, conjunctiva JAAD 35:260–262, 1996; AD 114:593– 594, 1978

Caterpillar dermatitis – conjunctivitis from caterpillar hairs (setae) (opththalmia nodosa) JAAD 62:1–10, 2010; Cutis 80:110–112, 2007; gypsy moth caterpillar – conjunctivitis with eyelid dermatitis NEJM 306:1301–1302, 1982 Cellulitis/erysipelas Chagas’ disease – American trypanosomiasis (Trypanosoma cruzi); Romana’s sign – unilateral painless bipalpebral edema of the eyelids, conjunctivitis, and inflammation of the lacrimal gland JAAD 60:897–925, 2009; JAAD 56:493, 2007 Chikungunya fever – fever, flush of face and upper chest, chills, severe pain in large joints; morbilliform eruption of the trunk, extensor surfaces with islands of sparing; burning pinnae, severe conjunctival injection; East Africa, India JAAD 58:308–316, 2008; Clin Inf Dis 20:225–231, 1995

Diphtheria

Ebola virus – high fever, body aches, myalgia, arthralgias, prostration, abdominal pain, watery diarrhea; disseminated intravascular coagulation Int J Dermatol 51:1037–1043, 2012; JAMA 287:2391–2002 Echovirus 16 Ehrlichiosis – conjunctivitis, morbilliform eruption, transient erythema, petechiae, purpura, TSS/Kawasaki's like eruption Ann Int Med 120:736–743, 1994 Endocarditis – subacute bacterial endocarditis; Osler’s nodes (painful hemorrhagic bulla of thumb tip); extensive distal purpura with necrosis of legs; Janeway lesion – purpuric macule of sole; conjunctival hemorrhage JAMA Derm 150:494–500, 2014; acute bacterial endocarditis

Chlamydia trachomatis – adult inclusion conjunctivitis JAMA 310:1721–1729, 2013

Enterobacter cloacae – septic cerebral venous thrombosis; retroauricular pain, retrobulbar pain, putrid nasal discharge, chills, double vision, unilateral edema and erythema of right eyelid, red eye NEJM 373:1553, 2015

Cobra spray

Enteroviral exanthema – personal observation

Coccidioidomycosis – episcleritis with erythema nodosum

Epidemic typhus (Rickettsia prowazeki) (body louse) – pink macules on sides of trunk, spreads centrifugally; flushed face with injected conjunctivae; then rash becomes deeper red, then purpuric; gangrene of finger, toes, genitalia, nose JAAD 2:359–373, 1980

Conjunctivitis   Adenoviral pharyngoconjunctival fever – type 3   Chlamydia trachomatis   Coccidioidomycosis  Cowpox (feline orthopoxvirus) – conjunctivitis, keratitis JAAD 49:513–518, 2003  Cryptococcosis – in AIDS; conjunctivitis Eye and Skin Disease, pp. 471, Lippincott, 1996  Demodicidosis (Demodex folliculorum) – demodex folliculitis; acneiform eruption with conjunctivitis and red face JAMA Derm 150:61–63, 2014   Epidemic keratoconjunctivitis – Adenovirus type 8   Mumps interstitial conjunctivitis    Pharyngoconjunctival fever – Adenovirus type 3   Secondary syphilis – iris roseata  Streptococcal   Tuberculous interstitial (parenchymal) conjunctivitis Cowpox (feline orthopoxvirus) – conjunctivitis, keratitis JAAD 49:513–518, 2003 Cryptococcosis – in AIDS; conjunctivitis Eye and Skin Disease, pp. 471, Lippincott, 1996 Cysticercosis JAAD 25:409–414, 1991 Cytomegalovirus – acute retinal necrosis; uveitis and central nervous system disease NEJM 380:1062–1071, 2019 Dacryocystitis (infection of the lacrimal sac) – acute or chronic Demodicidosis (Demodex folliculorum) – demodex folliculitis; acneiform eruption with conjunctivitis and red face JAMA Derm 150:61–63, 2014 Dengue hemorrhagic fever – conjunctival suffusion Clin Inf Dis 36:1004–1005,1074–1075, 2003; JAAD 46:430–433, 2002; Tyring, p.476, 2002; conjunctival hemorrhages Dermatol Clinics 29:33–38, 2011; hyperpigmentation of nose (chik sign); transient flushing, purpuric lesions, scleral injection, morbilliform exanthem with circular islands of sparing, aphthous ulcers, lichenoid papules, flagellated pigmentation, urticarial lesions, erythema multiforme-like Ped Derm 36:737–739, 2019; Indian Dermatol Online J 8:336–342, 2017; Indian J DV Leprol 76:671–676, 2010

Ethmoid sinusitis with periorbital cellulitis Filariasis Filoviruses – Marburg and Ebola virus; transient morbilliform rashes, purpura, red eyes; conjunctival injection, flushing, petechial rash, edema, purpura, ecchymoses JAAD 65:1213–1218, 2011; JAAD 49:979–1000, 2003 Fusarium – of sinuses; nasal erythema with conjunctivitis JAAD 47:659–666, 2002 Gonorrheal conjunctivitis – profuse purulent discharge; swollen hemorrhagic eyelids Hantavirus hemorrhagic fever Herpangina – conjunctivitis Curr Prob in Derm VIII:41–96, 1996 Herpes simplex – follicular conjunctivitis, episcleritis, stromal keratitis, dendritic ulcer, anterior uveitis, retinitis, central retinal vein occlusion, eczema herpeticum, periocular zosteriform eruption JAAD 70:795–819, 2014; JAMA 310:1721–1729, 2013; JAAD 57:737–763, 2007; J Virol 75:5069, 5075, 2001; Medicine 78:395– 409, 1999; Arch Ophthalmol 107:1155–1159, 1989; Nephron 50:368–370, 1988; Am J Med Sci 277:39–47, 1979; Kaposi's varicelliform eruption; acute retinal necrosis NEJM 380:1062–1071, 2019 Herpes zoster – acute retinal necrosis, optic neuritis, acute glaucoma, episcleritis, scleritis, keratitis NEJM 382:1750–1758, 2020; JAAD 70:795–819, 2014; NEJM 369;255–263, 2013; episcleritis, scleritis, keratitis JAMA 310:1721–1729, 2013; J Laryngol Otol 100:337–340, 1986; disseminated varicella-zoster infection – personal observation; acute retinal necrosis NEJM 380:1062–1071, 2019 Histoplasmosis Human papilloma virus Int J Oncol 54:1503–1510, 2019 Human T-lymphotrophic virus type 1-associated infective dermatitis – chronic relapsing dermatitis; severe red and exudative dermatitis with scaling and crusting of scalp, forehead, eyelids,

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paranasal area, neck, retroauricular, external ear, axillae, groin; chronic watery nasal discharge, crusting of anterior nares, blepharoconjunctivitis; generalized fine papular rash with lymph nodes; onset of rash at age 2 years; most common form of transmission is breast feeding; harbinger of development of adult T-cell lymphotropic leukemia and HTLV-1 associated myelopathy (HAM)/tropical spastic paralysis (TSP); Jamaica, Senegal, Brazil (endemic areas) JAAD 64:152–160, 2011; Lancet 336:1345–1347, 1990; Proc Natl Acad Sci USA 77:7415–7419, 1980; BJD 79:229– 236, 1967; BJD 78:93–100, 1966; uveitis and central nervous system disease NEJM 380:1062–1071, 2019 Infectious mononucleosis (Epstein-Barr virus) – conjunctivitis, keratitis, uveitis, choroiditis, retinitis, papillitis Clin Inf Dis 31:184– 188, 2000 Jellyfish envenomaton

and pustules, lymphadenopathy; heal with varioliform scarring JAAD 55:478–481, 2006 Moraxella osloensis Moths – Hylesia moths – contact with bristles results in erythematous papules, conjunctivitis, iritis, and keratitis JAAD 67:331–344, 2012 Murine typhus (Rickettsia typhi) – conjunctivitis MMWR 52:1224– 1226, 2003 Mycobacterium africanum (Mycobacterium tuberculosis complex) Mycobacterium bovis – conjunctivitis in milkmaids JAAD 43:535– 537, 2000 Mycobacterium kansasii – red nodule of bulbar conjunctivum BJD 152:727–734, 2005

Leptospirosis (Leptospira interrogans) MMWR 55:125–127, 2006; J Clin Inf Dis 21:1–8, 1995

Mycobacterium tuberculosis – scleritis NEJM 382:1750–1758, 2020; variable granulomatous intraocular disease JAMA Ophthalmol 134:233–234, 2016; JAAD 70:795–819, 2014; red eye with white plaque Clin Inf Dis 68:525–529, 2019; lupus vulgaris; starts as red-brown plaque, enlarges with serpiginous margin or as discoid plaques; apple-jelly nodules; conjunctival involvement with friable nodules which ulcerate Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960; papulonecrotic tuberculid – dusky red crusted or ulcerated papules occur in crops; associated with phlyctenular conjunctivitis Rook p.1199, 1998, Sixth Edition; Int J Dermatol 30:487–490, 1991; phlyctenular conjunctivitis with lichen scrofulosorum Ped Derm 17:373–376, 2000; AD Syphilol 29: 398–407, 1934; tuberculomas of conjunctiva; Parinaud's oculoglandular syndrome – granulomatous conjunctivitis with pre-auricular adenopathy; uveitis and central nervous system disease NEJM 380:1062–1071, 2019

Loiasis – Loa loa; Chrysops (deer fly, horse fly, mangrove fly) – adult worms in conjunctiva with unilateral palpebral edema JAAD 73:929–944, 2015; AD 108:835–836, 1973

Mycoplasma pneumonia-induced rash and mucositis (MIRM)– red eyes, red crusted lips, erythema of glans penis, targetoid lesions Lancet Inf Dis 17:562, 2017; Ped Derm 31:670–675, 2014

Lyme disease – scleritis NEJM 382:1750–1758, 2020; optic neuritis, periorbital edema; uveitis JAAD 70:795–819, 2014; Br J Ophthalmol 107:581–587, 2000; conjunctivitis leading to blindness, episcleritis, keratitis, iridocyclitis Adv Int Med 46:247–275, 2001; NEJM 321:586–596, 1989; AD 120:1017–1021, 1984; uveitis and central nervous system disease NEJM 380:1062–1071, 2019

Myiasis, ocular

Klebsiella pneumonia – hypopyon due to Klebsiella sepsis with endophthalmitis Clin Inf Dis 60:611,664–665, 2015 Leishmaniasis – Leishmania major uveitis Clin Inf Dis 34:1279– 1280, 2002; post kala azar dermal leishmaniasis – conjunctivitis BJD 157:1032–1036, 2007 Leprosy – lepromatous with infiltration of corneal nerves leading to anesthesia, infection, blindness Rook p.1225, 1998, Sixth Edition; lepromatous leprosy deposits causing keratitis, iridocyclitis, iris atrophy; erythema nodosum leprosum with iridocyclitis, uveitis, edema, and hyperemia resulting in painful red eye JAAD 83:17–30, 2020; JAAD 71:795–803, 2014; JAAD 51:416–426, 2004; AD 138:1607–1612, 2002

Lymphogranuloma venereum JAAD 41:511–529, 1999 Measles – diarrhea, headache, chills, myalgias, nausea and vomiting, red eyes, exanthema, enanthem, fever and rash JAAD 75:1–16, 2016; NEJM 372:2217, 2015; NEJM 372:2218–2223, 2015 Mediterranean spotted fever – Rickettsia conorii; morbilliform exanthem, spares the face, involves the palms and soles; petechial conjunctival lesions Ann NY Acad Sci 1166:167–171, 2009; Int J Med Sci 6:126–127, 2009 Meningococcal conjunctivitis and cellulitis Pediatrics 60:104–106, 1977; meningococcemia with orbital hemorrhage and DIC – periorbital edema and subconjunctival hemorrhage Eye 16(2):190–193, 2002; meningococcemia – conjunctivitis, conjunctival petechiae; chronic meningococcemia – conjunctivitis, iritis, retinitis BJD 153:669–671, 2005 Microsporidial conjunctivitis in HIV JAMA 275:1545, 1996 Millipede secretions – red eyes and mahogany pigmentation Cutis 67:452, 2001; periorbital edema, periorbital mahogany hyperpigmentation, conjunctivitis, keratitis JAAD 50:819–842, 2004 Molluscum contagiosum – chronic conjunctivitis and superficial punctate keratitis JAAD 70:795–819, 2014; Cutis 60:29–34, 1997 Monkeypox – fever, chills, headache, back pain, sore throat, myalgias, diaphoresis, cough, nausea, vomiting, nasal congestion, blepharitis, oral ulcers, centrifugally clustered umbilicated papules

North American blastomycosis Onchocerciasis – corneal inflammation around dead microfilariae leads to punctate keratitis, then sclerosing keratitis or iridocyclitis and possible blindness JAAD 70:795–819, 2014; AD 140:1161– 1166, 2004; Cutis 72:297–302, 2003; JAAD 45:435–437, 2001; Cutis 65:293–297, 2000; AD 133:381–386, 1997 Orf Am J Ophthalmol 97:601–604, 1984 Paederus beetle dermatitis – linear papular, vesicular, and pustular dermatitis JAAD 57:297–300, 2007; Cutis 69:277–279, 2002 Pappataci fever Paracoccidioidomycosis – conjunctival lesions Paragonimiasis – cold abscesses of conjunctivae Rev Ecuator Hig Med Trop 36:69–82, 1979 Parinaud's oculoglandular fever – leptospirosis, cat scratch disease, tuberculosis Parvovirus B19 – erythema infectiosum; bullous papular-purpuric gloves and socks syndrome – conjunctivitis JAAD 60:691–695, 2009 Phlebotomus sandfly fever Pediculosis capitis – conjunctivitis JAAD 50:1–12, 2004 Pediculosis pubis The Clinical Management of Itching; Parthenon; p. 55, 2000; Pentastomiasis, ocular – larval form of Armillifer species; ocular pain and blindness Clin Inf Dis 57:418,469–470, 2013 Pfiesteria piscicida – lakes, rivers, estuaries; contact dermatitis and conjunctivitis JAAD 61:733–750, 2009

Eyes, Red and Rash 367 Pinta Red tide dermatitis with conjunctivitis – Gymodinium breve and Alexandrium spp (aquatic dinoflagellate); due to brevetoxin and saxitoxin JAAD 61:733–750, 2009 Relapsing fever (tick-borne relapsing fever) – Ornithodoros soft ticks transmitting Borrelia hermsii, B.turicata, or B. parkeri; 1–2cm rose-­colored macules, papules, petechiae, purpura, facial flushing; arthralgias, iritis, myalgia JAAD 49:363–392, 2003; diffuse macular rash Rhinosporidiosis – conjunctivitis and eversions of eyelid Arch Otolaryngol 102:308–312, 1976 Rickettsial pox – personal observation Rocky Mountain spotted fever and other rickettsioses – conjunctival injection MMWR 65:1–44, May 13, 2016; MMWR 55:1–14, 2006

Tick-borne relapsing fever – Ornithodoros (soft tick); Borrelia genus; high fever in irregular pattern, chills, headache, myalgia, arthralgia, fatigue, macular rash, conjunctival injection, hepatosplenomegaly, epistaxis, meningeal signs Cutis 82:38–46, 2008; Pediatr Drugs 7:163–176, 2005 TORCH syndrome – congenital glaucoma with conjunctival hyperemia Toxic shock syndrome, either streptococcal or staphylococcal – widespread macular erythema, scarlatiniform, and papulopustular eruptions; occasional vesicles and bullae; edema of hands and feet; mucosal erythema with conjunctival erythema; second week morbilliform or urticarial eruption occurs with desquamation at 10–21 days JAAD 39:383–398, 1998; Rev Infect Dis 11(Suppl 1):S1–7, 1989; JAAD 8:343–347, 1983; Staphylococcus aureus MMWR 46:492, 1997

Roseola infantum

Toxocariasis – (T. canis, T. cati, T. leonensis) visceral larva migrans – ocular granuloma Surv Ophthalmol 28:361–381, 1984

Rubella – conjunctivitis

Toxoplasmosis, congenital (iridocyclitis) JAAD 12:697–706,1985

Rubeola

Trench fever (Bartonella quintana) – red macules, 1cm or less; headache, dizziness, fever lasting 4–8 days, malaise, chills, conjunctivitis, myalgias, arthralgias, severe shin pain, lymphadenopathy, evanescent rash; “culture negative endocarditis” JAAD 82:551–569, 2020; Clinics in Dermatol 28:483–488, 2010

Salmonella typhimurium – erythema nodosum and conjunctivitis Scand J Infect Dis 20:221–223, 1988 Schistosomal granuloma – ectopic granuloma of conjunctiva; uveitis and subretinal granulomas JAAD 70:795–819, 2014; Dermatol Clin 7:291–300, 1989 Scrub typhus (Rickettsia tsutsugamuchi) (mites) – headache and conjunctivitis; eschar with black crust; generalized macular or morbilliform rash JAAD 2:359–373, 1980 Severe fever with thrombocytopenia (STS bunyavirus) – fever, nausea and vomiting, abdominal pain, myalgia, lymphadenopathy, confusion, headache, conjunctival congestion, and cough NEJM 364:1523–1532, 2011 Smallpox Smallpox vaccination – vaccinia keratitis Clin Inf Dis 37:251–271, 2003 Sparganosis – Spirometra mansonoides – conjunctivitis Derm Clinics 17:151–185, 1999 Spiders – wolf spider (Lycosa species) spitting venom JAAD 44:561–573, 2001 Sporothrix schenckii var brasiliensis – red nodule of cheek with conjunctivitis BJD 172:1116–1119, 2015 Staphylococcal blepharitis with associated conjunctivitis Arch Ophthalmol 95:812–816, 1977 Staphylococcal scalded skin syndrome Staphylococcal toxic shock syndrome – personal observation Strongyloides hyperinfection – personal observation Subacute bacterial endocarditis Syphilis, secondary – scleritis NEJM 382:1750–1758, 2020; ocular syphilis NEJM 380:1062–1071, 2019; iris roseata; congenital – interstitial keratitis, iridocyclitis, choroidoretinitis, uveitis; syphilitic iritis occurs in 5% of patients with syphilis JAAD 70:795–819, 2014; Presse Med 19:369–371, 1990; JAAD 18:423–428, 1988; posterior uveitis Clin Inf Dis 32:1661–1673, 2001; malignant lues Int J STDs and AIDS 22:298–300, 2011; Sexually Transmitted Diseases Jan 2010;41–43; congenital syphilis – interstitial keratitis, irregular pupil, photophobia JAAD 70:795–819, 2014 Tarantula hairs – New World tarantula flicks urticating hairs from the dorsal abdomen giving ophthalmia nodosa (“tarantula eyes”) Iran J Med Sci 182:349–350, 2013; Arch Ophthalmol 117:1096–1097, 1999; South Med J 91:565–567, 1998; Arch Dis Child 75:462–463, 1996

Trichinosis – periorbital edema, chemosis (conjunctivitis) NEJM 351:487, 2004; transient morbilliform eruption, splinter hemorrhages Can J Public Health 88:52–56, 1997; Postgrad Med 97:137–139, 143–144, 1995; South Med J 81:1056–1058, 1988 Trypanosomiasis, American – Romana's sign Tularemia, oculoglandular – conjunctivitis MMWR 62:963–966, 2013; Dermatol Clinics 22:313–320, 2004; Photodermatology 2:122–123, 1985 Typhoid fever Typhus (louse, flea, tick) Vaccinia – conjunctival autoinoculation MMWR 52:180–181, 191, 2003; Varicella Verruca vulgaris – conjunctivitis or keratitis Arch Ophthalmol 42:365–372, 1949 Viral hemorrhagic fevers – including Argentine hemorrhagic fever, Bolivian hemorrhagic fever, Lassa fever (arenavirus) – morbilliform or petechial rash with conjunctivitis J Infect Dis 155:445–455, 1985; Venezuelan hemorrhagic fever, hemorrhagic fever with renal syndrome (Hantavirus), Congo-Crimean-Congo hemorrhagic fever (conjunctival injection); Kyasanur Forest disease (Flavivirus) – conjunctival injection; hemorrhagic exanthem, papulovesicular palatine lesions; Omsk hemorrhagic fever, Rift Valley fever – conjunctivae injected; yellow fever, dengue fever, Ebola or Marburg virus infection Dermatol Clinics 17:29–40, 1999 Viral syndrome with conjunctivitis West Nile virus infection – uveitis and central nervous system disease NEJM 380:1062–1071, 2019 Whipple’s disease Yaws Zika virus – fever, pinpoint red papules coalescing into morbilliform (macular and papular exanthem) eruption, arthralgia, palmar desquamation; conjunctivitis, myalgia, headache, retro-orbital pain, edema; palatal petechiae; microcephaly; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) MMWR 65:1161–1165, 2016; JAAD 75:1–16, 2016; JAMA Derm 152:691–693, 2016; Clin Inf Dis 61:1445,1485–1486, 2015; NEJM 360:2536–2543, 2009;

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micropapular eruption of face with conjunctival injection JAMA Derm 153:326–327, 2018; uveitis and central nervous system disease NEJM 380:1062–1071, 2019

INFILTRATIVE DISORDERS Hypereosinophilic syndrome – palpebral conjunctival ulcers AD 132:535–541, 1996 Juvenile colloid milium – conjunctivitis JAAD 49:1185–1188, 2003 Juvenile xanthogranuloma – hemorrhage into anterior chamber, uveitis, iritis Optom Vis Sci 92:126–133, 2015; congenital glaucoma with conjunctival hyperemia; hyphema of eye JAAD 34:445–449, 1996; JAAD 36:355–367, 1997 Langerhans cell histiocytosis Int Med Case Rep J 11:65–68, 2018 Progressive nodular histiocytosis – conjunctival papule JAAD 57:1031–1045, 2007 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – yellowish infiltrates with conjunctival injection BJD 149:1085–1086, 2003; Clinic Exp Dermatol 27:277–279, 2002; bilateral uveitis JAAD 51:931–939, 2004; uveitis, blepharoconjunctivitis BJD 148:1060–1061, 2003; chronic uveitis Ped Derm 17:377– 380, 2000

and papules, facial erythema, red macules and patches; scattered indurated nodules, photoeruptions; leukocytoclastic vasculitis; pruritus, conjunctival injection, oral ulcers, alopecia NEJM 369:2333–2343, 2013; Int J Dermatol 51:564–567, 2012; Indian J Otolaryngol Head Neck Surg 63:Suppl 1:110–112, 2011; Arch Pathol Lab Med 134:289–293, 2010; Clin Rheumatol 26:50–54, 2007; BJD 144:885–889, 2001 Polymyalgia rheumatica/temporal arteritis Posterior scleritis presenting as red eye (VZV, sarcoidosis, choroidal tumors, melanoma, hemangioma, metastases) Pyoderma gangrenosum – keratitis JAAD 76:512–518, 2017; conjunctival involvement Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988; peripheral ulcerative keratitis associated with neutrophilic disorders JAAD 40:331–334, 1999; nodular scleritis Ophthalmology 109:1941–1943, 2002; bullous pyoderma gangrenosum Pyostomatitis vegetans Rosai-Dorfman disease – clustered erythematous papules of thigh; associated with uveitis Practical Dermatol August 2014, pp.56,60

INFLAMMATORY DISORDERS

Sarcoid, including erythrodermic sarcoid – conjunctivitis, iridocyclitis, uveitis and central nervous system disease NEJM 380:1062– 1071, 2019; JAAD 70:795–819, 2014; Lofgren’s syndrome – erythema nodosum, bilateral hilar adenopathy, acute iridocyclitis; Heerfordt’s syndrome – uveitis, parotid gland enlargement, fever, cranial nerve palsies (facial nerve); keratoconjunctivitis sicca with parotid and lacrimal gland enlargement Clin Dermatol 4:129–135, 1986

Ankylosing spondylitis – anterior uveitis NEJM 380:1062–1071, 2019; Eur J Intern Med22:554–560, 2011

Toxic epidermal necrolysis BMJ Case Rep Oct 12, 2018; BJD 113:597–560, 1985

CAPS (cryopyrin-associated periodic syndromes) – familial cold autoinflammatory syndrome, Muckle-Wells syndrome, neonatal onset multisystem inflammatory disorder (NOMID) – non-pruritic urticarial-like papules, confluent geographic plaques; conjunctivitis, episcleritis, uveitis; sensorineural hearing loss, chronic meningitis; secondary amyloidosis; IL-1beta increased; mutations in NLRP3 gene (CIAS1) (cold-induced autoinflammatory syndrome 1) or NALP3 (NACHT domain-, leucine-rich repeat-, and PYD-containing protein JAAD 68:834–853, 2013

Vernal keratoconjunctivitis – confluent cobblestoned papillae in upper palpebral conjunctivae NEJM 370:1636, 2014

Cutaneous sinus histiocytosis – chronic uveitis Ped Derm 17:377– 380, 2000

Ciliary neuralgia – unilateral periorbital headache with lacrimation and conjunctival injection with unilateral flushing of the face Crohn’s disease – uveitis, conjunctivitis NEJM 380:1062–1071, 2019; Arch Int Med 148:297–302, 1988 Deficiency of interleukin-1 receptor antagonist (DIRA) – autosomal recessive; life threatening systemic inflammation with bone and skin involvement; anonychia; chronic cutaneous pustulosis resembling pustular psoriasis; bone lesions include lytic bone lesions, periostitis, osteopenia, long bone epiphyseal ballooning and erosions, widening of clavicle and anterior rib ends, periosteal elevation, heterotopic ossification; vascular occlusions, interstitial pulmonary fibrosis; red eyes AD 148:301–304, 2012 Erythema multiforme major (Stevens-Johnson syndrome) – conjunctivitis, corneal erosions, symblepharon JAAD 70:795–819, 2014; Ped Derm 23:546–555, 2006; JAAD 25:69–79, 1991; Dermatologica 171:383–396, 1985; Am J Med 44:390–405, 1968 Erythema nodosum – scleritis and phlyctenular conjunctivitis JAAD 45:163–183, 2001 Fuchs’ heterochromic iridocyclitis Cutis 43:49–51, 1989 Inflamed pinguecula – personal observation Kikuchi-Fujimoto disease – young Asians; fever, lymphadenopathy, respiratory symptoms, arthralgias and myalgias; ulcers, red plaques,

METABOLIC Acrodermatitis enteropathica – conjunctivitis, photophobia Ped Derm 19:426–431, 2002; Ped Derm 19:180–182, 2002; AD 116:562–564, 1980; Dermatologica 156:155–166, 1978; acquired zinc deficiency Addison’s disease Angiokeratoma corporis diffusum (Fabry’s disease (alpha galactosidase A; deficient lysosomal alpha N-acetylgalactosaminidase) – X-linked recessive AD 129:460–465, 1993; initially, telangiectatic macules; tortuous conjunctival vessels NEJM 276:1163–1167, 1967 Biotin deficiency NEJM 304:820–823, 1981 Biotinidase deficiency – keratoconjunctivitis Ped Derm 21:231–235, 2004 Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 167:988–900, 2012 Cushing’s disease Cystic fibrosis Disseminated intravascular coagulation – retiform purpura JAAD 82:783–796, 2020

Eyes, Red and Rash 369 Fabry’s disease – angiokeratoma corporis diffusum; accumulation of globotriaosylceramide Ped Derm 28:727–728, 2011

Carcinoid syndrome – personal observation

Gout – scleritis

Epibulbar complex choristoma with nevus sebaceus Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.211

Hartnup’s disease

Iris nevi in atypical mole syndrome AD 129:198–201, 1993

Hemoglobinopathies – retiform purpura JAAD 82:783–796, 2020

Juvenile xanthogranuloma – anterior uveitis and glaucoma Ped Derm 26:232–234, 2009

Fucosidosis type III – bulbar conjunctival telangiectasias

Hemolytic uremic syndrome – retiform purpura JAAD 82:783–796, 2020 Hyperthyroidism – Graves exophthalmos Hyperviscosity syndrome Hypothyroidism Hypoparathyroidism (keratoconjunctivitis) Hypoplasminogenemia – autosomal recessive; ligneous conjunctivitis with red eyes, ligneous periodontitis, blindness, tooth loss; decreased wound healing JAMA Derm 150:1227–1228, 2014

Kaposi’s sarcoma – conjunctival Kaposi’s sarcoma JAAD 59:179– 206, 2008; JAAD 28: 371–395, 1993; AD 125:357–361, 1989; JAMA 275:1545, 1996 Leukemia – congenital leukemia cutis AD 129:1301–1306, 1993; chronic lymphocytic leukemia; T-cell prolymphocytic leukemia AD 148:1199–1204, 2012 Lipoma – personal observation

Nephrogenic fibrosing dermopathy JAAD 48:42–47, 2003

Lymphoma – HTLV I/II leukemia/lymphoma – conjunctivitis JAAD 38:502, 1998; cutaneous T-cell lymphoma – keratitis, uveitis Arch Ophthalmol 99:272–274, 1981

Plasminogen deficiency – rare autosomal recessive; thick wood-like pseudomembranes on mucosal surfaces ligneous conjunctivitis J Throm Thrombolysis 43:132–138, 2017

Melanoma – ciliary body melanoma AD 139:1067–1073, 2003; amelanotic melanoma of bulbar conjunctivum Cutis 77:377–381, 2006

Porphyria – porphyria cutanea tarda – keratoconjunctivitis; congenital erythropoietic porphyria – keratoconjunctivitis, corneal inflammation, keratomalacia blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, cataracts JAAD 67:1093–1110, 2012; Ped Derm 28:416–420, 2011; Ped Derm 20:498–501, 2003; Semin Liver Dis 2:154–63, 1982; erythropoietic protoporphyria; variegate porphyria

Metastatic carcinoma to the iris Orbital tumors Plasmacytoma – retrobulbar NEJM 345:1917, 2001 Polycythemia vera Sebaceous gland carcinoma – may present as blepharoconjunctivitis JAAD 33:1–15, 1995

Post-menopausal flushing Prolidase deficiency – keratitis Renal failure Riboflavin deficiency – conjunctivitis and periorificial dermatitis (seborrheic dermatitis-like) Ped Derm 16:95–102, 1999 Scurvy – conjunctival hemorrhage Int J Dermatol 45:909–913, 2006; JAAD 41:895–906, 1999; NEJM 314:892–902, 1986 Thrombotic thrombocytopenic purpura – retiform purpura JAAD 82:783–796, 2020 Tyrosinemia type II (Richner-Hanhart syndrome) – autosomal recessive; painful focal palmoplantar keratoderma, photophobia, dendritic (herpetiform) corneal erosions, mental retardation; severe nail dystrophy due to onychophagia, diagnosis by tandem mass spectrometry; increased serum and urine tyrosine and no succinylacetone in urine (only seen in type I tyrosinemia) BJD 160:704–706, 2009; Ped Derm 25:378–380, 2008; Curr Prob Derm 14:71–116, 2002; Ped Derm 14:110–112, 1997; JAAD 35:857–859, 1996 Vitamin A deficiency with xerophthalmia NEJM 370:159–166, 2014; Clinics in Derm 17:457–461, 1999; NEJM 331:551, 1994 Vitamin B2 deficiency (riboflavin deficiency) – conjunctivitis and periorificial dermatitis (seborrheic dermatitis–like) Ped Derm 16:95–102, 1999; Clinics in Derm 17:457–461, 1999 Vitamin B6 deficiency – conjunctivitis Clinics in Derm 17:457–461, 1999 Vitamin B12 deficiency JAAD 15:1263–1274, 1986 Vitamins A, C, and D deficiency – red eyes, rash, purulent crusting and discharge NEJM 370:159–166, 2014

PARANEOPLASTIC Necrobiotic xanthogranuloma with paraproteinemia – episcleritis and uveitis; red-yellow plaques – periorbital and on trunk and extremities Am J Dermatopathol 34:644–647, 2012; Clin Ophthalmol 6:2045–2047, 2012; AD 147:1215–1220, 2011; JAAD 56:302–316, 2007; Am J Ophthalmol 129:651–657, 2000; Can J Ophthalmol 32:396–399, 1997; conjunctivitis, keratitis, uveitis, iritis AD 128:94–100, 1992 Paraneoplastic pemphigus – conjunctivitis JAAD 70:795–819, 2014; BJD 160:468–470, 2009; AD 141:1285–1293, 2005; Cutis 61:94– 96, 1998; Dermatol Clin 10:557–571, 1992; NEJM 323:1729–1735, 1990; paraneoplastic IgA pemphigus – tense bullae, vesicopustules JAAD 56:S73–76, 2007

PHOTOSENSITIVITY Actinic prurigo – cheilitis, conjunctivitis, eyebrow alopecia, dermatitis, facial scars SKINmed 13:287–295, 2015; The Dermatologist May, 2015, pp47–48, 50, 2015; JAAD 67:1093–1110, 2012 Dermatol Ther 16:40–44, 2003; BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683– 692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981 Chronic actinic dermatitis Hydroa vacciniforme -keratoconjunctivitis Cutis 88:245–253, 2011; JAAD 42:208–213, 2000; Ped Derm 4:320–324, 1988 Phototoxic drug eruption

Wilson’s disease

NEOPLASTIC Bowen’s disease

PRIMARY CUTANEOUS DISEASE Acne rosacea (ocular rosacea) – dry eye, blepharitis, conjunctivitis, scleritis, telangiectasia, episcleritis, chalazion, hordeolum, punctate

370 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 keratitis, iritis, iridocyclitis, meibomitis, corneal thinning, corneal neovascularization, corneal scarring, corneal perforation Ped Derm 32:522–525, 2015; JAAD 70:795–819, 2014; Cutis 92:234–240, 2013; Eur J Ophthalmol 10:11–14, 2000; Arch Ophthalmol 111:228–230. 1993; Am J Ophthalmol 88:618–622, 1979; Surv Ophthalmol 31:145–158, 1986; Am J Ophthalmol 88:618–622, 1979; BJD 65:458–463, 1953; keratoconjunctivitis sicca AD 134:679–683, 1998; JAAD 26:211–214, 1992; Atopic dermatitis – atopic keratoconjunctivitis, keratoconus JAAD 77:280–286, 2017; JAAD 70:795–819, 2014; Ophthalmology 98:150–158, 1991; hay fever and atopic dermatitis Arch Dis Child 81:225–230, 1999; vernal catarrh (conjunctivitis) Congenital erosive and vesicular dermatitis with reticulate supple scarring – conjunctivitis JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995 Epidermolysis bullosa, including dominant or recessive dystrophic – corneal erosions BJD 146:267–274, 2002; symblepharon Epidermolysis Bullosa: Basic and Clinical Aspects. New York: Springer, 1992: 135–151; J R Soc Med 81:576–578, 1988; AD 124:762–764, 1988; epidermolysis bullosa atrophicans inversa JAAD 13:252–278, 1985; junctional EB, Herlitz type, junctional EB non-Herlitz type, generalized, laryngo-­onycho-­cutaneous syndrome, recessive dystrophic, severe generalized, recessive dystrophic, generalized other JAAD 58:931–950, 2008 Erythrokeratoderma variabilis – chronic keratoconjunctivitis Ophthalmology 105:1478–1484, 1998

2004; Am J Opthalmol 136:239–243, 2003; conjunctivitis J Fr Ophthalmol 6:51–57, 1983 Non-bullous CIE (congenital ichthyosiform erythroderma) (erythrodermic lamellar ichthyosis) – autosomal recessive – ectropion AD 121:477–488, 1985 Palmoplantar pustulosis (pustulotic arthro-osteitis) – episcleritis JAAD 41:845–846, 1999 Pityriasis rubra pilaris Psoriasis – pustular psoriasis JAAD 13:828–829, 1985; psoriasis with blepharitis, conjunctivitis, episcleritis, keratitis, anterior uveitis, pigment dispersion, cataract, cystoid macular edema, symblepharon, trichiasis Clin in Dermatol 37:663–667, 2019; JAAD 70:795– 819, 2014; Int J Dermatol 52:554–559, 2013; JAAD 65:1202–1212, 2011; Psoriasis Forum 17:169–179, 2011; ulcerative keratitis BJD 170:746–748, 2014; Trans Am Ophthalmol Soc 127:270, 1979; Ann Rheum Dis 35:354, 1976; acute anterior uveitis Clin Exp Dermatol 44:924–926, 2019; Am J Ophthalmol 139:106–111, 2005; chronic uveitis with psoriatic arthritis Acta DV (Stockh) 64:557–559, 1984 Ocular rosacea – personal observation Pustular rosacea – personal observation Rosacea fulminans – acute pustular eruption of face; red eyes BJD 163:877–879, 2010; AD 41:451–462, 1940 Seborrheic dermatitis with blepharitis and conjunctivitis Vitiligo – uveitis JAAD 4:528–536, 1981; JAAD 38:647–666, 1998

Erythroderma from a variety of causes Hailey-Hailey disease AD 39:679–685, 1939 Harlequin fetus (ichthyosis congenital fetalis) – severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis – ectropion JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982 Hydroa vacciniforme – conjunctivitis Ped Derm 21:555–557, 2004; Ped Derm 4:320–324, 1987 Ichthyosis – conjunctivitis JAAD 70:795–819, 2014 Keratosis follicularis spinulosa decalvans – keratitis, conjunctivitis, corneal scarring – X-linked dominant and autosomal dominant Ped Derm 21:14–17, 2004 Keratosis lichenoides chronica (Nekam’s disease) – reticulated flat-­topped keratotic papules, linear arrays, atrophy, comedo-like lesions, prominent telangiectasia; conjunctival injection, scarring eye lesions including blepharitis, conjunctivitis, iridocyclitis, keratoconjunctivitis, anterior uveitis; seborrheic dermatitis-like eruption; acral dermatitis over toes; punctate keratotic papules of palmar creases; scaly red papules of face; seborrheic dermatitis-like rash of face; nail dystrophy; oral and genital erosions, conjunctivitis AD 147:1317–1322, 2011; Cutis 86:245–248, 2010; Ped Derm 26:615–616, 2009; AD 145:867–69, 2009; AD 144:405–410, 2008; Am J Dermatopathol 28:260–275, 2006; JAAD 49:511–513, 2003; Dermatology 201:261–264, 2000; JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; Dermatopathol Pract Concept 3:310–312 1997; AD 131:609–614, 1995; Dermatology 191:188–192, 1995; AD 105:739–743, 1972; Presse Med 51:1000–1003, 1938; Arch Dermatol Syph (Berlin) 31:1–32, 1895; in children JAAD 56:S1–5, 2007 Lamellar ichthyosis – ectropion with exposure keratitis Lichen planus – chronic keratoconjunctivitis AD 148:224–227, 2012; AD 147:465–467, 2011; J Eur Acad Dermatol Venereol 25:100–104, 2011; Br J Ophthalmol 90:1325–1326, 2006; Cornea 23:100–105,

SYNDROMES Albinism – personal observation Alport’s syndrome Ankyloblepharon-ectrodactyly-cleft lip/palate (AEC) syndrome – conjunctivitis AD 141:1591–1594, 2005 Ataxia telangiectasia – autosomal recessive; telangiectasias of face, ocular telangiectasia, extensor surfaces of arms and bulbar conjunctiva; café au lait macules, hypopigmented macules, melanocytic nevi, facial papulosquamous rash, hypertrichosis, bird-like facies; immunodeficiency, increased risk of leukemia, lymphoma; cerebellar ataxia with eye movement signs, mental retardation, and other neurologic defects; cafe au lait macules JAAD 68:932–936, 2013; Ann Int Med 99:367–379, 1983 Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) – keratoconjunctivitis; enamel hypoplasia; sparse scalp, facial, and body hair, chronic mucocutaneous candidiasis, adrenal insufficiency, hypoparathyroidism, nail dystrophy, vitiligo; mutation in autoimmune regulator gene (AIRE) Ped Derm 24:529–533, 2007 Behcet’s disease – relapsing iritis, conjunctivitis, episcleritis, keratitis, anterior or posterior uveitis; uveitis and central nervous system disease NEJM 380:1062–1071, 2019; JAAD 79:987–1006, 2018; JAAD 70:795–819, 2014; BJD 157:901–906, 2007; JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999; JAAD 36:689–696, 1997 Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; uveitis, iritis, vitritis, closed angle glaucoma; translucent skin-colored papules (non-caseating granulomas) of trunk and extremities with uveitis, iritis, synovitis, arthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints) mutations in NOD2 (nucleotide-­binding oligomerization domain 2) (caspase

Eyes, Red and Rash 371 recruitment domain family, member 15; CARD 15) JAAD 68:834– 853, 2013; AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996; chromosome 16p12–q21 JAAD 49:299–302, 2003; Am J Hum Genet 76:217–221, 1998; Am J Hum Genet 59:1097–1107, 1996 Bloom’s syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; blisters of nose and cheeks; slender face, prominent nose; facial telangiectatic erythema with involvement of eyelids, ear, hand and forearms; bulbar conjunctival telangiectasias; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy; no neurologic deficits Ped Derm 22:147–150, 2005; Curr Prob Derm 14:41–70, 2002; Ped Derm 14:120–124, 1997; JAAD 17:479–488, 1987; AD 114:755–760, 1978; Clin Genet 12:85–96, 1977; Am J Hum Genet 21:196–227, 1969; Am J Dis Child 116:409–413, 1968; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks and arms, chondritis with progressive ear and saddle nose deformities, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, splenomegaly, protuberant abdomen JAAD 62:489–495, 2010 Carcinoid syndrome JAAD 68:189–209, 2013; JAAD 46:161–183, 2002 Chronic infantile neurological cutaneous articular syndrome (CINCA) (Neonatal onset multisystem inflammatory disorder (NOMID)) – urticarial rash at birth, arthropathy, uveitis, mental retardation, short stature AD 136:431–433, 2000; J Pediatr 99:79–83, 1981; Eur J Ped 156:624–626, 1997 Ciliary neuralgia (cluster headaches) – conjunctival injection and unilateral flushing Cockayne’s syndrome Congenital plasminogen deficiency – autosomal recessive; red eyes, oral ulcers, gingival edema; chronic mucosal pseudomembranous lesions with white membranes of gingivae, and eyelids; blepharitis, gingival hyperplasia, leukoplakia, ligneous conjunctivitis with red eyes; thick nodular eyelids; ligneous periodontitis, blindness, tooth loss; decreased wound healing JAMA Derm 150:1227– 12228, 2014; Ped Derm 448–451, 2009 Costello syndrome JAAD 32:904–907, 1995 Degos’ disease Dermochondrocorneal dystrophy (Francois syndrome) AD 124:424– 428, 1988 Didymosis aplasticosebacea – aplasia cutis congenita in a nevus sebaceus (Schimmelpenning syndrome); coloboma of eyelid Ped 24:514–516, 2007 Down’s syndrome Dyskeratosis benigna intraepithelialis mucosae et cutis hereditaria – conjunctivitis, umbilicated keratotic nodules of scrotum, buttocks, trunk; palmoplantar verruca-like lesions, leukoplakia of buccal mucosa, hypertrophic gingivitis, tooth loss J Cutan Pathol 5:105– 115, 1978 Dyskeratosis congenita (Zinsser-Cole-Engmann syndrome) – X-linked recessive – cutaneous atrophy and pigmentation; mental retardation, short stature, deafness, conjunctivitis with obstruction of lacrimal ducts, blepharitis, palmoplantar keratoderma, palmoplantar hyperhidrosis, urethral anomalies, esophageal stenosis, choanal

atresia, hepatic abnormalities, frontal lobe atrophy, intracranial calcifications, hypogonadism, osteoporosis, avascuar necrosis Ped Derm 26:176–179, 2009; J Med Genet 12:339–354, 1975 Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome (EEC syndrome) – keratoconjunctivitis Ped Derm 20:113–118, 2003; Am J Ophthalmol 78:211–216, 1974 Ectodermal dysplasia - autosomal recessive ectodermal dysplasia with corkscrew hairs, pili torti, syndactyly, keratosis pilaris, onychodysplasia, dental abnormalities, conjunctival erythema, palmoplantar keratoderma, cleft lip or palate JAAD 27:917–921, 1992 Encephalocraniocutaneous lipomatosis – red soft plaque of bulbar conjunctiva (limbal dermoids) (pterygium like lesion) lipomatous hamartomas of scalp and eyelids; linear yellow papules of forehead extending to eyelids; alopecia and ocular choristomas; ophthalmologic manifestations; seizures, mental retardation; mandibular or maxillary ossifying fibromas and odontomas; cranial asymmetry; developmental delay, mental retardation, seizures, spasms of contralateral limbs; unilateral porocephalic cysts with cortical atrophy Ped Derm 30:491–492, 2013; Ped Derm 23:27–30, 2006; Ped Derm 22:206–209, 2005; JAAD 47:S196–200, 2002; Am J Med Genet 191:261–266, 2000; JAAD 37:102–104, 1998; BJD 104:89– 96, 1981; Arch Neurol 22:144–155, 1970 Fabry’s disease – tortuous blood vessels of bulbar conjunctiva; whorled corneal opacity; alpha galactosidase A deficiency JAAD 79:795–819, 2014; AD 140:1440–1446, 2004 Familial cold autoinflammatory syndrome (cold urticaria) – nonpruritic urticarial rash precipitated by cold; conjunctivitis, arthralgias of knees and ankles and arthritis; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin); CIAS1 Ped Derm 24:85–89, 2007; AD 142:1591–1597, 2006; JAAD 54:319– 321, 2006; BJD 150:1029–1031, 2004; JAMA 114:1067–1068, 1940; CAPS (cryopyrin-­associated periodic syndromes) – familial cold autoinflammatory syndrome, Muckle-Wells syndrome, neonatal onset multisystem inflammatory disorder (NOMID) – non-pruritic urticarial-like papules, confluent geographic plaques; conjunctivitis, episcleritis, uveitis; sensorineural hearing loss, chronic meningitis; secondary amyloidosis; IL-1beta increased; mutations in NLRP3 gene (CIAS1) (cold-induced autoinflammatory syndrome 1) or NALP3 (NACHT domain-, leucine-rich repeat-, and PYD-containing protein JAAD 68:834–853, 2013 Familial histiocytic dermoarthritis – uveitis, arthritis Floppy eyelid syndrome BJD 151:706, 2004 Granulomatous synovitis, uveitis, and cranial neuropathies – JABS syndrome J Pediatr 117:403–408, 1990 H syndrome – autosomal recessive; facial telangiectasias; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, short stature, facial telangiectasia, gynecomastia, camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly; Arabic Palestinian population; gluteal lipoatrophy; hyperpigmentation, hearing loss, diabetes mellitus, lymphadenopathy, hypertrichosis, heart anomalies, micropenis, hallus valgus, hyperpigmentation induration and hypertrichosis of inner thighs and shins (sclerodermoid), chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 JAAD 70;80–88, 2014;JAAD 59:79–85, 2008 Hemophagocytic lymphohistiocytosis syndrome (HLH) with peripheral T-cell lymphoma – personal observation Hereditary mucoepithelial dysplasia (dyskeratosis) (Gap junction disease, Witkop disease) (hereditary benign intra-epithelial

372 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 dyskeratoses (Witkop-von Sallmann syndrome) – conjunctivitis; leukoplakia of buccal mucosa, lips, tongue in Haliwa-Saponi Native Americans of North Carolina) – dry rough skin; red eyes, non-scarring alopecia, keratosis pilaris, erythema of oral (hard palate, gingival, tongue) and nasal mucous membranes, cervix, vagina, and urethra; perineal and perigenital psoriasiform dermatitis; increased risk of infections, fibrocystic lung disease Ped Derm 29:311–315, 2012; BJD 153:310–318, 2005; JAAD 45:634–636, 2001; Ped Derm 11:133–138, 1994; Am J Med Genet 39:338–341, 1991; JAAD 21:351–357, 1989; Am J Hum Genet 31:414–427, 1979; Oral Surg Oral Med Oral Pathol 46:645–657, 1978; Arch Pathol 70:696–711, 1960 Hypereosinophilic syndrome – lymphocytic HES associated with cardiac endomyocardial fibrosis with restrictive cardiomyopathy Hyper IgE syndrome Ped Derm 9:410–413, 1992; vernal conjunctivitis Ophthalmology 91:1213–1216, 1984 HID syndrome (hystrix-like ichthyosis with deafness) – autosomal dominant; shark-skin appearance, sensorineural deafness, spiky and cobblestoned hyperkeratosis, neonatal erythroderma, scarring alopecia, occasional punctate keratitis; probably variant of KID syndrome with mutation of connexin 26 (gap junction protein) BJD 146:938–942, 2002 Ichthyosis follicularis with atrichia and photophobia (IFAP) – collodion membrane and erythema at birth; generalized follicular keratoses, non-scarring alopecia, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis and corneal vascularization JAAD 70:795–819, 2014; BJD 142:157–162, 2000; AD 125:103–106, 1989; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999 Incontinentia pigmenti – iritis, uveitis JAAD 47:169–187, 2002; Curr Prob in Derm VII:143–198, 1995; AD 112:535–542, 1976 Job syndrome – chronic keratoconjunctivitis Kawasaki’s disease – non-suppurative conjunctivitis; conjunctival injection with sparing of the limbic region; scleral injection JAAD 69:501–510, 2013; macular, morbilliform, urticarial, scarlatiniform, erythema multiforme-like, pustular, erythema marginatum-like exanthems; strawberry tongue; cheilitis; edematous hands with lamellar desquamation; myocarditis and coronary artery thrombosis and aneurysms; arthralgia, arthritis JAAD 39:383–398, 1998; Jpn J Allergol 16:178–222, 1967 Keratosis-ichthyosis-deafness (KID) syndrome – reticulated severe diffuse hyperkeratosis of palms and soles, well marginated, serpiginous erythematous verrucous plaques, perioral furrows, leukoplakia, sensory deafness, photophobia with vascularizing keratitis, blindness Ped Derm 29:349–357, 2012; Ped Derm 23:81–83,2006; Clin in Dermatol 23:23–32, 2005; JAAD 23:385– 388, 1990; AD 123:777–782, 1987; AD 117:285–289, 1981 Keratosis follicularis spinulosa decalvans – conjunctivitis; keratosis pilaris, follicular atrophoderma, facial erythema, scarring alopecia, ulerythema oophyrogenes, photophobia JAAD 58:499–502, 2008; Arch Dermatol Syphilol 151:384–387, 1926 Laryngo-onycho-cutaneous syndrome – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3 (LAMA3A) BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedica 2:15–25, 1986; Ped Derm 24:306–308, 2007; Ped Derm 23:75–77, 2006; Cornea 20:753–756, 2001; Arch Dis Child 70:319–326, 1994;

JAAD 29:906–909, 1993; Clin Dysmorphol 1:3–14, 1992; Eye 5:717–722, 1991 Lipoid proteinosis JAAD 14:367–371, 1986 MAGIC syndrome – combination of relapsing polychondritis and Behcet’s syndrome AD 126:940–944, 1990 Muckle-Wells syndrome – autosomal dominant; macular erythema (evanescent red macules), urticaria (cold air urticaria), deafness, extremity pain, arthralgias of knees and ankles with arthritis; nephropathy, AA amyloidosis with neuropathy; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin) AD 142:1591–1597, 2006; BJD 151:99–104, 2004; JAAD 39:290–291, 1998; QJMed 31:235–248, 1962; CAPS (cryopyrin-associated periodic syndromes) – familial cold autoinflammatory syndrome, Muckle-Wells syndrome, neonatal onset multisystem inflammatory disorder (NOMID) – non-­pruritic urticarial-like papules, confluent geographic plaques; conjunctivitis, episcleritis, uveitis; sensorineural hearing loss, chronic meningitis; secondary amyloidosis; IL-1beta increased; mutations in NLRP3 gene (CIAS1) (cold-induced autoinflammatory syndrome 1) or NALP3 (NACHT domain-, leucine-rich repeat-, and PYD-containing protein JAAD 68:834–853, 2013 Mucoepithelial dysplasia (gap junction disease) – simulates candidal infection, dry rough skin, keratosis pilaris, thin scalp hair, perleche, keratoconjunctivitis Genetic Skin Disorders, Second Edition, 2010,pp.698–700 Multiple mucosal neuroma syndrome (MEN IIB) (Gorlin’s syndrome) – keratitis due to decreased tear production Can J Ophthalmol 11:290–294, 1976; skin-colored papules and nodules of lips, tongue, oral mucosa JAAD 36:296–300, 1997; Oral Surg 51:516–523, 1981; J Pediatr 86:77–83, 1975; Am J Med 31:163– 166, 1961 Mulvihill-Smith syndrome – short stature, microcephaly, unusual facies, multiple pigmented nevi, hypodontia, immunodeficiency with chronic infections, high pitched voice, progeroid, conjunctivitis, delayed puberty J Med Genet 31:707–711, 1994 Neurofibromatosis – congenital glaucoma with conjunctival hyperemia Neutral lipid storage disease (Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma; thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness JAAD 17:801–808, 1987; AD 121:1000–1008, 1985 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – urticarial lesions, chronic meningitis, arthralgias of knees and ankles with deforming arthropathy with epiphyseal bone formation, deafness, hepatosplenomegaly, uveitis, vitreitis, papilledema, corneal stromal keratopathy; mental retardation; fever and rash more severe in evening; mutation in NALP3 (CIAS 1) which encodes cryopyrin AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319–321, 2006; Ped Derm 22:222– 226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005; CAPS (cryopyrin-associated periodic syndromes) – familial cold autoinflammatory syndrome, Muckle-Wells syndrome, neonatal onset multisystem inflammatory disorder (NOMID) – non-pruritic urticarial-like papules, confluent geographic plaques; conjunctivitis, episcleritis, uveitis; sensorineural hearing loss, chronic meningitis; secondary amyloidosis; IL-1beta increased; mutations in NLRP3 gene (CIAS1) (cold-induced autoinflammatory syndrome 1) or NALP3 (NACHT domain-, leucine-rich repeat-, and PYD-containing protein JAAD 68:834–853, 2013

Eyes, Red and Rash 373 Oligodontia, keratitis, skin ulceration, and arthroosteolysis Am J Med Genet 15:205–210, 1983 Osteogenesis imperfect – personal observation Pseudoacromegaly – autosomal recessive; skin ulcers, arthro-osteolysis, keratitis, oligodontia Am J Med Genet 15:205–210, 1983 Rapp-Hodgkin ectodermal dysplasia – congenital, autosomal dominant, ectodermal dysplasia, distinctive craniofacial features, cleft lip or palate and hypospadias in males; scalp dermatitis Ped Derm 7:126–131, 1990; Ped Derm 14:149–150, 1997 Recalcitrant erythematous desquamating (RED) syndrome – diffuse macular erythema, ocular and mucosal erythema, strawberry tongue, delayed desquamation in the setting of AIDS JAAD 39:383–398, 1998 Reactive arthritis syndrome – erosions with marginal erythema; circinate erosions JAAD 59:113–121, 2008; NEJM 309:1606–1615, 1983; Semin Arthritis Rheum 3:253–286, 1974; Dtsch Med Wochenschr 42:1535–1536, 1916   Circinate balanitis – annular or serpiginous   Asymptomatic oral mucosal erosions  Keratoderma blenorrhagicum; soles, pretibial areas, dorsal toes, feet, fingers, hands, nails, scalp; may be associated with HIV disease Ann Int Med 106:19–26, 1987; Semin Arthritis Rheum 3:253–286, 1974; following gastroenteritis due to Salmonella enteritidis, Shigella, Yersinia, Campylobacter species, and Clostridium difficile Clin Inf Dis 33:1010–1014, 2001   Pustular psoriasis   Psoriasiform plaques   Nail changes   Geographic tongue   Aortic insufficiency   Cardiac conduction abnormalities  Conjunctivitis, uveitis, keratitis – sterile mucopurulent discharge Ophthalmology 93:350–356, 1986; Ann Rheum Dis 38(Suppl.):8– 11, 1979   IgA nephropathy  Myelopathy Palatal erosions, oral ulcers, glossitis  Seronegative non-suppurative arthritis – polyarticular knees, ankles, metatarsophalangeal, sacroiliac joints; relative sparing of hands and wrists; occasionally monoarticular; enthesitis  Spondylitis   Achilles tendonitis   Plantar fasciitis   Sausage digits – dactylitis  Urethritis  Ulcerative vulvitis – red crusted plaques of vulva and perineum JAAD 48:613–616, 2003; Arch Int Med 145:822–824, 1985; Ophthalmology 93:350–356, 1986; Ann Rheum Dis 38(Suppl.):8– 11, 1979 Relapsing polychondritis – scleritis NEJM 373:2562, 2015; iritis, conjunctivitis, episcleritis Medicine 80:173–179, 2001; Eye and Skin Disease, pp.239–242, Lippincott, 1996; Medicine 55:193–216, 1976; Arch Gen Med 14:29–34, 1869 Richner-Hanhart syndrome (tyrosinemia type II) – autosomal recessive; tyrosine aminotransferase deficiency; chromosome 16q22-q24; painful palmoplantar keratoderma with circumscribed keratoses, bullae may occur; dendritic corneal ulcers, mental retardation; palmoplantar hyperhidrosis; signs include tearing, redness, pain and photophobia progressing to superficial and deep

dendritic ulcers; mental retardation; aggregated tonofibril bundles on electron microscopy; crystal structures JAAD 70:795–819, 2014; Ped Derm 23:259–261, 2006; J Pediatr 126:266–269, 1995; AD 130:507–511, 1994; Ann DV 120:139–142, 1993; Dermatol 182:168–171, 1991; AD 126:1342–1346, 1990; herpetiform erosions and dendritic ulcers JAAD 35:857–859, 1997 Sjogren's syndrome – keratoconjunctivitis sicca Spangler-Tappeiner syndrome Sturge-Weber syndrome – episcleral telangiectasia with facial nevus flammeus Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.117; congenital glaucoma with conjunctival hyperemia Sweet's syndrome – conjunctivitis, episcleritis, occlusive venous vasculitis, and inflammatory glaucoma Clin Exp Ophthalmol 35:858–860, 2007; AD 145:216–218, 2009; Clin Exp Dermatol 25:352–353, 2000; JAAD 40:331–334, 1999; J Rheumatol 23:1995– 1998, 1996; JAAD 31:835–836, 1994; JAAD 31:535–556, 1994; BJD 76:349–356, 1964 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) – erythematous patches, tender red plaques, fever, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia, abdominal pain, headache; Irish and Scottish predominance; mutation in TNFRSF1A – gene encoding 55kDa TNF receptor JAAD 68:834– 853, 2013; AD 136:1487–1494, 2000; Mayo Clin Proc 72:806–817, 1997 Vernal keratoconjunctivitis – trichomegaly Ped Derm 26:188–193, 2009; vernal keratoconjunctivitis – confluent cobblestoned papillae in upper palpebral conjunctivae NEJM 370:1636, 2014 Vogt-Koyanagi-Harada syndrome – granulomatous panuveitis; uveitis and central nervous system disease NEJM 380:1062–1071, 2019; Ped Derm 34:612–613, 2017; Autoimmun Rev 13:550–555, 2014; Ped Derm 31:99–101, 2014; JAAD 69:625–633, 2013; Eye and Skin Disease, pp.303–309, Lippincott, 1996 Wells' syndrome – iritis Int J Dermatol 31:672, 1992 Wyburn-Mason syndrome (Bonnet-Dechaume-Blanc syndrome) X-linked reticulate pigmentary disorder with systemic manifestations (familial cutaneous amyloidosis) (Partington syndrome II) – X-linked; rare; Xp21-22; boys with generalized reticulated muddy brown pigmentation (dyschromatosis) with hypopigmented corneal dystrophy (dyskeratosis), coarse unruly hair, unswept eyebrows, silvery hair, hypohidrosis, recurrent pneumonia with chronic obstructive disease, clubbing; failure to thrive, female carriers with linear macular nevoid Blaschko-esque hyperpigmentation Ped Derm 32:871–872, 2015; Am J Med Genet 161:1414–1420, 2013; Eur J Dermatol 18:102–103, 2008; Ped Derm 22:122–126, 2005; Semin Cut Med Surg 16:72–80, 1997; Am J Med Gen 10:65:1981 Xeroderma pigmentosum – conjunctivitis; acute sunburn, persistent erythema, freckling – initially discrete, then fuse to irregular patches of hyperpigmentation, dryness on sun-exposed areas; with time telangiectasias and small angiomas, atrophic white macules develop; vesiculobullous lesions, superficial ulcers lead to scarring, ectropion; multiple malignancies; photophobia, conjunctivitis, ectropion, symblepharon, neurologic abnormalities; short stature,

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conjunctivitis, photophobia, pyogenic granulomas in toddlers JAAD 75:855–870, 2016; BJD 168:1109–1113, 2013; JAAD 59:881–886, 2008; BJD 152:545–551, 2005; Adv Genet 43:71–102, 2001; Hum Mutat 14:9–22, 1999; Mol Med Today 5:86–94, 1999; Derm Surg 23:447–455, 1997; Dermatol Clin 13:169–209, 1995; Recent Results Cancer Res 128:275–297, 1993; AD 123:241–250, 1987; Ann Int Med 80:221–248, 1974; XP variant AD 128:1233–1237, 1992

Capillary malformation Carotid artery-cavernous sinus fistula Eosinophilic granulomatosis with polyangiitis Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.319; Degos' disease (malignant atrophic papulosis) – bulbar conjunctival involvement JAAD 38:852–856, 1998; Sem Derm 14:99–105, 1995 Fat emboli

TOXINS Alkali burn Arsenic poisoning – acute; subconjunctival bleeding Dermatol Clinics 29:45–51, 2011; BJD 149:757–762, 2003 Mustard gas exposure AD 128:775–780, 1992; JAAD 38:187–190, 1998; JAAD 19:529–536, 1988 Radiation dermatitis Scombroid fish poisoning

TRAUMATIC

Granulomatosis with polyangiitis – keratoconjunctivitis, granulomatous scleritis or uveitis NEJM 382:1750–1758, 2020; NEJM 380:1062–1071, 2019; NEJM 352:392, 2005; JAAD 49:335–337, 2003; Mayo Clin Proc 60:227–232, 1985; scleritis Hemangioma Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) Rook p.2091, 1998, Sixth Edition; Am J Med 82:989–997, 1987 Disseminated hemangiomatosis Lemierre’s syndrome – swollen red eyelid; due to Fusobacterium necrophorum; cavernous sinus thrombophlebitis, carotid artery thromboarteritis, abscess of parotid gland and subperiosteal orbit NEJM 371:2018–2027, 2014

Asphyxia – facial congestion, facial edema, cyanosis, periorbital or conjunctival petechiae JAAD 64811–824, 2011

Leukocytoclastic vasculitis – personal observation

Burns – chemical, thermal, sunburn

Polyarteritis nodosa, systemic – keratitis and corneal ulcers Arch Ophthalmol 48:1–11, 1952; infantile – conjunctivitis JAAD 53:724– 728, 2005; JAMA 217:1666–1670, 1971, J Pediatr 120:206–209, 1992; fibrinous iridocyclitis; scleritis

Lightning strike – Lichtenberg figures; frond-like (ferning pattern) transient non-blanching pink-red erythema beginning 20 minutes to 3 ½ hours after the strike and lasting up to 48 hours Cutis 80:141– 143, 2007; Arch Neurol 61:977, 2005; Injury 34:367–371, 2003; NEJM 343:1536, 2000; Burns Incl Thermal Inj 13:141–146, 1987; Proc IEE 123:1163–1180, 1976; Memoirs Med Soc London 2:493–507, 1794 Physical trauma Radiation therapy – Cancer Nurs 16:371–381, 1993 Traumatic asphyxia with petechiae JAAD 23:972–974, 1990 Ultraviolet B radiation – conjunctivitis and photokeratitis Dermatol Clin 10:483–504, 1992 Valsalva maneuver – facial petechiae and conjunctival hemorrhage; subconjunctival hemorrhage from sneezing – viral exanthem

Phakomatosis pigmentovascularis

Port wine stain of eyelid associated with dilated conjunctival vessels Can J Ophthalmol 10:136–139, 1975 Primary pulmonary hypertension Sturge-Weber syndrome Superior vena cava syndrome Cutis 79:362–367–368, 2007; Am Rev Respir Dis 141:1114–1118, 1990; AD 128:953–956, 1992 Urticarial vasculitis – conjunctivitis, uveitis, episcleritis with urticarial vasculitis JAAD 49:S283–285, 2003; JAAD 38:899–905, 1998; JAAD 26:441–448, 1992; Arthr Rheum 32: 1119–1127, 1989; hypocomplementemic vasculitis – iritis, uveitis, episcleritis JAAD 48:311–340, 2003 Vasculitis – peripheral ulcerative keratitis associated with neutrophilic disorders (pustular vasculitis) JAAD 40:331–334, 1999

VASCULAR Anti-phospholipid antibody syndrome

FACIAL ASYMMETRY

Hemimaxillofacial dysplasia (segmental odontomaxillary dysplasia) (HATS – hemimaxillary enlargement, asymmetry of face, skin findings)– facial asymmetry, hypertrichosis of the face, unilateral maxillary enlargement, partial anodontia, delayed eruption of teeth, gingival thickening of affected segment, Becker’s nevus, hairy nevus (hypertrichosis), lip hypopigmentation, depression of cheek, erythema, hypoplastic teeth Ped Derm 21:448–451, 2004; JAAD 48:161–179, 2003; Oral Surg Oral Med Oral Pathol 64:445–448, 1987

AUTOIMMUNE DISEASES Linear morphea- en coup de sabre Mayo Clin Proc 70:1068–1076, 1995 Lupus panniculitis (lupus profundus) AD 73:15–53, 1956

Multiple mucosal neuroma syndrome – open bite deformity (skeletal apertognathia) JAAD 77:809–830, 2017

CONGENITAL DEFECTS

Neurofibromatosis

Congenital facial nerve palsy

Parry-Romberg syndrome Ped Derm 36:223–226, 2019

Craniofacial microsomia

PIK3CA-related overgrowth spectrum (PROS) Cureus 12:e6586, 2020

Craniosynostosis Ectopic thymus, congenital – unilateral swelling of face Society of Pediatric Dermatology Annual Meeting, July, 2015

TRAUMA Traumatic lipoatrophy – personal observation

DRUGS Anti-retroviral therapy (HAART) Dermatol Surg 28:979–986, 2002

VASCULAR LESIONS CLAPO syndrome – capillary malformation of lower lip; lymphatic malformation of face and neck; swollen lip, prominent veins of neck, jaw and scalp, asymmetry of face and limbs, partial or generalized overgrowth, reticulate erythema of neck; PIK3CA mutation Ped Derm 35:681–682, 2018

INFECTIONS AND INFESTATIONS Bell’s palsy – due to herpes zoster; cranial nerve VII NEJM 369;255–263, 2013; due to herpes simplex – personal observation; Lyme disease Herpes simplex infection – facial nerve paralysis NEJM 370:1048, 2014

Lymphatic malformation Neurofibromatosis – plexiform neurofibroma of face Port wine stain Sturge-Weber syndrome – personal observation

INFLAMMATORY DISORDERS Heerfordt’s syndrome – uveoparotid fever; parotid gland enlargement, uveitis, fever, cranial nerve palsies (facial nerve)

FACIAL DERMATITIS, SCALY

Lipoatrophy Ramsey-Hunt syndrome NEJM 369;255–263, 2013;

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Cutis 91:181–184, 2013 Sarcoidosis – neurosarcoid – personal observation

Allergic contact dermatitis – fragrances, preservatives, skin care products, medications, occupational, cosmetics JAAD 41:435–442, 1999; sunscreens Contact Dermatitis 37:221–232, 1997; Compositae dermatitis; woods nail polish Contact Dermatitis 34:140–141, 1996; acrylic nails cell phones (nickel) Clin Exp Dermatol 35:201, 2010; Cutis 84:199–200, 2009; bindi dermatitis Contact Derm 47:55, 2002; Int J Dermtol 25:434–435, 1986; allergic contact dermatitis to nickel with id reaction – follicular facial dermatitis Ped Derm 28:276–280, 2011; cell phone dermatitis – allergic contact dermatitis to nickel Ped Derm 28:327–331, 2011; Clin Exp Dermatol 35:201, 2010; Indian marking nut Dermatitis 27:72–73, 2016

Syphilis, secondary – cranial nerve III involvement – personal observation

NEOPLASTIC DISORDERS Adult T-cell lymphoblastic leukemia – facial nerve palsy Ped Derm 31:393–395, 2014 Facial tumors Spindle cell lipoma – facial asymmetry with deviated nasal tip JAMADerm 156:210–211, 2020

Amicrobial pustulosis associated with autoimmune disease treated with zinc BJD 143:1306–1310, 2000

SYNDROMES Goeminne syndrome – X-linked incompletely dominant, multiple melanocytic nevi, multiple spontaneous keloids, basal cell carcinomas, varicose veins, muscular torticollis, renal dysplasia, cryptorchidism, urethral meatal stenosis, facial asymmetry, clinodactyly, scoliosis, dental caries Curr Prob in Derm VII:143–198, 1995; JAAD 29:373–388, 1993

Bullous pemphigoid – seborrheic pemphigoid Clin Dermatol 5:6–12, 1987; Hautarzt 31:18–20, 1980 Chronic granulomatous disease – seborrheic dermatitis-like AD 130:105–110, 1994 Chronic mucocutaneous candidiasis Genetic Skin Disorders, Second Edition, 2010, pp. 6689–692

Goldenhar syndrome

Cicatricial pemphigoid

Goltz’s syndrome – personal observation

Dermatomyositis Curr Opin Rheum 11:475–482, 1999

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Dermatitis herpetiformis

EXOGENOUS AGENTS

Fogo selvagem – seborrheic dermatitis-like eruption JAAD 20:657–659, 1989

Airborne allergic contact dermatitis Contact Derm 18:183–390, 2007; Clin Dermatol 16:27–31, 1998; JAAD 15:1–10, 1986

Hyper IgE syndrome (Job’s syndrome) Lupus erythematosus – systemic, subacute cutaneous; Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – butterfly rash, facial dermatitis, exanthema, papules, annular, atypical targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAMADerm 153:461–462, 2017; Dermatol Online J Aug 15, 2009; BJD 142:343–346, 2000; Clin Exp Dermatol 24:74–77, 1999; JAAD 21:374–377, 1989: AD 88:176–180, 1963 Mixed connective tissue disease Am J Dermatopathol 19:206–213, 1997 Pemphigus – El-Bagre endemic pemphigus; facial scaling and crusting, conjunctival injection, eyelid erythema and edema, ectropion, meibomitis JAAD 62:437–447, 2010 Pemphigus erythematosus (Senear-Usher syndrome) Int J Derm 24:16–25, 1985; AD 13:761–781, 1926 Pemphigus foliaceus – starts in seborrheic distribution AD 83:52– 70, 1961 Severe combined immunodeficiency – seborrheic dermatitis-like eruption Birth Defects 19:65–72, 1983

Amyl nitrate Clin Exp Dermatol 37:587–588, 2012 Food allergy – seborrheic dermatitis-like eruption Fragrance Clin Exp Dermatol 37:587–588, 2012 Irritant contact dermatitis Peppers Clin Exp Dermatol 37:587–588, 2012 Shiitake mushroom toxicoderma – seborrheic dermatitis-like eruption JAAD 24:64–66, 1991 Sorbic acid in cosmetics Cutis 40:395–397, 1987

INFECTIONS AND INFESTATIONS Demodicidosis, papulonodular Diphtheria – crusts around nose and mouth with faucial diphtheria Schweiz Rundsch Med Prax 87:1188–1190, 1998; Postgrad Med J 72:619–620, 1996; Am J Epidemiol 102:179–184, 1975 Eczema herpeticum BJD 114:575–582, 1986 Eczema vaccinatum Herpes simplex infection, chronic Herpes zoster infection, chronic

CONGENITAL LESIONS Congenital erosive and vesicular dermatosis with reticulate supple scarring – widespread erosions, low set ears, syndactyly Ped Derm 24:384–386, 2007; Ped Derm 22:55–59, 2005; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; AD 134:1121–1124, 1998; Dermatol 194:278–280, 1997; JAAD 32:873–877, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985; AD 86:52–61, 1962

DRUG-INDUCED Corticosteroids – inhaled corticosteroids (budesonide) Clin Exp Allergy 23:232–233, 1993 Drug hypersensitivity syndrome

HIV disease – personal observation HTLV-1 infective dermatitis BJD 150:958–965, 2004 Impetigo contagiosum Infectious eczematoid dermatitis Leishmaniasis – espundia (mucocutaneous leishmaniasis) – facial edema, erythema, verrucous plaques, dermatitis, edema of lips Am J Trop Med Hyg 59:49–52, 1998 Leprosy – autoaggressive Hansen's disease JAAD 17:1042–1046, 1987 Pyoderma – crusted dermatitis due to Serratia marcescens JAAD 58:S109–110, 2008 Staphylococcal pyoderma Tinea barbae – Trichophyton verrucosum Clin Infect Dis 23:1308– 1310, 1996

Dupilumab – facial erythema, facial dermatitis developing after initiation of dupilumab JAAD 82:230–232, 2020

Tinea faciei; generalized dermatophytosis; tinea incognito

Fixed drug eruption

Toxic shock syndrome

5-fluorouracil

Trichodysplasia spinulosa (polyoma virus)

Tinea versicolor Mycoses 34:345–347, 1991

Hydantoin pseudolymphoma Hydroxyurea – dermatomyositis-like scaling eruption of face, hands and feet AD 135:818–820, 1999

INFILTRATIVE DISEASES

Lansoprazole (PPI) – allergic contact dermatitis J Allergy Clin Immunol 111:155, 2003

Langerhans histiocytosis in adults – seborrheic dermatitis-like eruption

Multiple drugs Proton pump inhibitors – airborne contact dermatitis; red face and neck Dermatitis 26:287–290, 2015

INFLAMMATORY DISEASES

Retinoid dermatitis, topical or systemic

Eosinophilic pustular folliculitis of infancy – dermatitis with or without pustules Ped Derm 21:615–616, 2004

Toxic epidermal necrolysis

Erythema multiforme

Uracil-tegafur – DLE-like lesion Eur J Dermatol 11:54–57, 2001

Sarcoid

Retinoids, topical

Superficial granulomatous pyoderma

Facial Dermatitis, Scaly

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METABOLIC

Erythromelanosis follicularis faciei JAAD 34:714, 1996

Acrodermatitis enteropathica J Dermatol 24:135–136, 1997; BJD 121:773–778, 1989

Granuloma faciale

Biotin deficiency Semin Dermatol 10:296–302, 1991; with multiple carboxylase deficiency Ped Derm 21:231–235, 2014

Hydroa vacciniforme – vesiculopapular eruption of face BJD 173:801–805, 2015

Pellagra

Ichthyosis, acquired

Kwashiokor – perinasal erosions Cutis 67:321–327, 2001

Impetigo herpetiformis

Necrolytic migratory erythema Int J Dermatol 49:24–29, 2010; AD 113:792–797, 1977

Keratosis lichenoides chronica – facial erythematosquamous lesions JAAD 28:870–873, 1993; JAAD 2:217–220, 1980

Nutritional deficiency associated with anorexia nervosa AD 140:521–524, 2004

Lamellar ichthyosis

Pyridoxine deficiency – seborrheic dermatitis-like eruption

Periorbital dermatitis (variant of perioral dermatitis) – idiopathic or topical corticosteroid-associated; including facial Afro-Caribbean childhood eruption (FACE) BJD 91:435–438, 1976

Riboflavin deficiency – seborrheic dermatitis-like eruption JAAD 21:1–30, 1989

Granulosis rubra nasi

Lichen simplex chronicus

Pityriasis alba

NEOPLASTIC HTLV-1 leukemia/lymphoma – hyperpigmented facial dermatitis and infective dermatitis around nose and ears HTLV; infective dermatitis of scalp, eyelid margins, axillae, groin; generalized papular dermatitis AD 134:439–444, 1998; Lancet 336:1345–1347, 1990; BJD 79:229–236, 1967; BJD 78:93–100, 1966 Lentigo maligna Cutis 40:357–359, 1987 Lymphoma – cutaneous T-cell lymphoma – including perioral scaly dermatitis BJD 132:671–673, 1995

PARANEOPLASTIC DISORDERS Bazex syndrome (acrokeratosis paraneoplastica) – scaly dermatitis of face and nose Cutis 55:233–236, 1995 Myeloma-associated follicular spicules of face JAMADerm 151:82– 84, 2015

PHOTODERMATITIS Actinic lichen planus Ann DV 121:635–638, 1994(French); JAAD 20:226–231, 1989 Actinic prurigo – cheilitis, conjunctivitis, eyebrow alopecia, dermatitis, facial scars SKINmed 13:287–295, 2015; JAAD 67:1093–1110, 2012 BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Australas J Dermatol 42:192–195, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981 Chronic actinic dermatitis JAAD 21:205–214, 1989 Euphorbia trigona – phytophotodermatitis SKINmed 12:253–255, 2014 HIV disease photodermatitis – personal observation Photoallergic contact dermatitis – sunscreens Contact Dermatitis 37:221–232, 1997 Phototoxic/allergic drug rash Polymorphic light eruption

PRIMARY CUTANEOUS DISEASE Acanthosis nigricans

Pityriasis rosea Pityriasis rubra pilaris – seborrheic dermatitis-like eruption Ped Derm 3:446–451, 1986 Psoriasis Seborrheic dermatitis – petalloid, AIDS-associated Seborrheic dermatitis-like eruptions   Acrodermatitis enteropathica   Anorexia nervosa Dermatol Endocrinol1:268–270, 2009  Dermatomyositis  Drugs   Cetuxinib   Erlotinib    5-fluorouracil (systemic or topical)   Gefitinib   Interferon   Interleukin   Onsatinib J Clin Aesthet Dermatol 10:23–27, 2017   Sorafinib   Thalidomide   Vemurafenib   Fogo selvagem JAAD 20:657–659, 1989   Graft vs host disease Ped Derm 33:e195–197, 2016  HIV/AIDS JAAD 14:242–248, 1986   Glucagonoma syndrome JAAD 12:1032–1039, 1985   Hyper IgE syndrome   Keratosis lichenoides chronica Ped Derm 29:511–512, 2012   Langerhans histiocytosis in adults   Lupus erythematosus, systemic   Mixed connective tissue disease   Pemphigus foliaceus   Pityriasis rubra pilaris Ped Derm 3:446–451, 1986   Pyridoxine deficiency   Riboflavin deficiency JAAD 21:1–30, 1989  Seborrheic pemphigoid Clin Dermatol 5:6–12, 1987; Hautarzt 31:18–20, 1980  Severe combined immunodeficiency Birth Defects 19:65–72, 1983   Shiitake mushroom toxicoderma JAAD 24:64–66, 1991  Tinea faciei Ped Derm 22:243–244, 2005; JAAD 29:119–120, 1993

PSYCHOCUTANEOUS

Atopic dermatitis

Anorexia nervosa – acquired zinc deficiency Ped Derm 9:268–271, 1992

Darier's disease

Factitial dermatitis Am J Ophthalmol 128:392–394, 1999

Epidermolytic hyperkeratosis

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SYNDROMES Cardio-facio-cutaneous syndrome (NS) – xerosis/ichthyosis, eczematous dermatitis, alopecia, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, nevi, keratosis pilaris, autosomal dominant, patchy or widespread ichthyosiform eruption, sparse scalp hair and eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects Ped Derm 17:231– 234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990

Still’s disease JAAD 58:533–535, 2008

CONGENITAL Cystic hygroma (lymphatic malformation) Ectopic thymus – unilateral swelling of face Society of Pediatric Dermatology Annual Meeting, July, 2015 Facial hemihypertrophy Hemangioma

Dubowitz syndrome – autosomal recessive, erythema and scaling of face and extremities in infancy, sparse blond scalp and eyebrow hair, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities Am J Med Genet 63:277–289, 1996

Sturge-Weber syndrome

Gianotti-Crosti syndrome (Epstein-Barr virus) – papular facial dermatitis with lymphadenopathy JAAD 72:1–19, 2015

Syringomyelia – hemifacial edema Clin Exp Dermatol 13:42–45, 1988

Glucagonoma syndrome – seborrheic dermatitis-like eruption JAAD 12:1032–1039, 1985 Hyper IgE syndrome Ped Derm 9:410–413, 1992 Kawasaki’s disease Netherton’s syndrome Olmsted's syndrome Am J Dis Child 383:757, 1927 Wiskott-Aldrich syndrome Eur J Pediatr 152:998–1000, 1993

TOXINS Acrodynia (pink disease) AD 124:107–109, 1988

TRAUMA Airbag dermatitis J Dermatol 27:685–686, 2000 Burn Radiation dermatitis

VASCULAR Takayasu's arteritis – scaly erythema Facial Edema JAAD 37:346–348, 1997; NEJM 328:1625–1631, 1993

FACIAL EDEMA  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

DEGENERATIVE DISEASES

DRUGS Angiotensin converting enzyme (ACE) inhibitor-induced angioedema – face and oral mucosa BJD 136:153–158, 1997 Anticonvulsant hypersensitivity syndrome Ped Derm 19:142–145, 2002; phenytoin reaction Cutis 61:101–102, 1998 Corticosteroids – topical corticosteroid abuse with Cushing’s syndrome – personal observation Drug reaction with eosinophilia and systemic symptoms (DRESS) – morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, facial edema, lymphadenopathy Clin in Dermatol 38:63–78, 2020; Ped Derm 36:324–329, 2019; BJD 169:1071–1080, 2013; BJD 168:1130–1132, 2013; JAAD 68:693–705, 2013; AD 146:1373– 1379, 2010; AD 145:63–66, 2009; due to anti-convulsants Ped Derm 26:536–546, 2009; allopurinol Ped Derm 27:270–273, 2010 Drug eruptions, multiple drugs – including hypersensitivity syndromes Cutis 77:353–357, 2006; acute exanthematous pustular eruptions Fidoxamicin (macrolide antibiotic) – facial, tongue, and throat swelling Clin Inf Dis 58:537–538, 2014 Imatinib (Gleevec) (multikinase inhibitor) – edema of eyelids and face JAAD 58:545–570, 2008 Isotretinoin (Accutane) – acute facial erythema and edema Ped Derm 23:518–519, 2006 Kit and BCR-ABL inhibitors – imatinib, nilotibib, dasatinib – facial edema morbilliform eruptions, pigmentary changes, lichenoid reactions, psoriasis, pityriasis rosea, pustular eruptions, DRESS, Stevens-Johnson syndrome, urticarial, neutrophilic dermatoses, photosensitivity, pseudolymphoma, porphyria cutanea tarda, small vessel vasculitis, panniculitis, perforating folliculitis, erythroderma JAAD 72:203–218, 2015

Acute allergic contact dermatitis – latex Clin in Dermatol 38:63–78, 2020; Contact Dermatitis 36:229–230, 1997; chronic facial edema due to palladium dental crowns

Sorafenib BJD 161:1045–1051, 2009

Contact Dermatitis 40:226–227, 1999

Vemurafinib – erythema and edema of face and neck BJD 169:934– 938, 2013

Angioedema Clin in Dermatol 38:63–78, 2020; JAAD 25:155–161, 1991

Sunitinib (multikinase inhibitor) BJD 161:1045–1051, 2009; JAAD 58:545–570, 2008

Dermatomyositis Clin in Dermatol 38:63–78, 2020; Otolaryngol Head Neck Surg 93:673–677, 1985

EXOGENOUS AGENTS

Lupus erythematosus – systemic lupus erythematosus BJD 135:355–362, 1996; Br J Oral Maxillofacial Surg 26:129–142, 1988; Ann DV 113:1249–1250, 1986; as presenting sign of systemic lupus erythematosus JAAD 56:S126–127, 2007

Iododerma in chronic renal failure – marked facial edema and edema of eyelids; pustulovesicular eruption, pustules, pseudovesicles, vegetative plaques AD 140:1393–1398, 2004; JAAD 36:1014–1016, 1997; Clin Exp Dermatol 15:232–233, 1990; BJD 97:567–569, 1977

FACIAL EDEMA Hyaluronic acid filler – facial erythema and edema JAAD 73:15–24, 2015 Peanut allergy Cutis 65:285–289, 2000 Polymethylmethacrylate filler – treatment with interferon-alpha and ribavirin; persistent severe facial edema AD 143:507–510, 2007 Silicone granuloma (paraffinoma) – nodule of glabella with recurrent facial edema; hepatosplenomegaly, pulmonary fibrosis AD 148:385–390, 2012 Sodium hypochlorite irrigation during root canal AD 132:231–233, 1996

INFECTIONS AND INFESTATIONS Actinomycosis Oral Maxillofac Surg 16:403–404, 2012 African trypanosomiasis Anthrax – Bacillus anthracis; malignant pustule; painless ulcer with vesicular lesions; face, neck, hands, fingers, arms, foot, knee; starts as painless erythema evolving into papule then into multiple vesicles or bulla on red base; then ulcer with hemorrhagic crust (eschar) with edema and erythema with small vesicles; edema of surrounding skin; takes six weeks to heal; edema of eyelids, lips, perioral area; slaughtering or milking of ill cows, sheep, or goats; handling of raw meat Ped Derm 27:600–606, 2010; Ped Derm 18:456–457, 2001; Br J Opthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981 Arenaviruses (hemorrhagic fevers) – Lassa fever (rats and mice) (West Africa), Junin virus (Argentine pampas), Machupo virus (Bolivian savannas), Guanarito virus (Venezuela), Sabia virus (Southeast Brazil), Whitewater virus (California, New Mexico), Tacaribe virus complex (mice) – swelling of face and neck, oral hemorrhagic bullae, red eyes JAAD 49:979–1000, 2003

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Leishmaniasis – espundia (mucocutaneous leishmaniasis) – facial edema, erythema, verrucous plaques, dermatitis, edema of lips Am J Trop Med Hyg 59:49–52, 1998 Leprosy – lepromatous; type 1 or type 2 reaction in borderline; type 1 reaction demonstrates reappearance of resolved lesions, acute peripheral neuritis, edema of hands, feet, and face BJD 167:29–35, 2012; JAAD 57:914–917, 2007; JAAD 51:417–426, 2004 Mucormycosis, rhinocerebral – Rhizopus, Apophyosmyces, Cunninghamella, Absidia, Rhizomucor Clin Inf Dis 40:990–996, 2005; J Neurol Sci 143:19–30, 1996; unilateral localized facial edema with slight erythema; within days goes on to necrosis JAAD 66:975–984, 2012; ptosis with upper eyelid edema and necrosis JAMA 309:2382–2383, 2013 Mumps – unilateral facial and jaw swelling MMWR 61:986–989, 2012 Mycobacterium tuberculosis – lupus vulgaris Myiasis, nasal Onchocerciasis, acute – coastal erysipelas (erysipelas de la costa); facial edema AD 133:381–386, 1997 Phlegmon – personal observation Pseudomonas aeruginosa – ecthyma gangrenosum with severe facial edema AD 142:1663–1664, 2006 Pythium insidiosum (pythiosis) (alga) (aquatic oocyte) – necrotizing hemorrhagic plaque; ascending gangrene of legs; Thailand; painful subcutaneous nodules, eyelid swelling and periorbital cellulitis, facial swelling, ulcer of arm or leg, pustules evolving into ulcers BJD 175:394–397, 2016; J Infect Dis 159:274–280, 1989 Roseola infantum (exanthem subitum) – human herpesvirus 6 – periorbital edema Pediatrics 93:104–108, 1994

Balamuthiasis (Balamuthia mandrillaris) – amoebic infection of soft tissues and central nervous system; edematous erythematous infiltrated plaque of face, abdomen, extremities Advances Dermatol 23:335–350, 2007

Serratia marcescens

Clostridium sordelli – malignant edema Pan Afr Med J June 12, 2018

Staphylococcus aureus – palatal necrosis

Conididobolus coronatus

Sycosis barbae

Cowpox

Tick-borne lymphadenopathy (Rickettsia slovaca, R. rioja, R. raoultii); Dermacentor marginatus – scalp eschar with facial edema; residual alopecia JAAD 75:1–16, 2016

Crimean-Congo hemorrhagic fever – flushing and edema of face and neck Ebola virus Eczema vaccinatum – small pox vaccination; vesicles, pustules, swollen face with vesicles and eschar (progressive vaccinia, vaccinia necrosum, vaccinia gangrenosum) in patients with cell mediated immune defects Cutis 101:87–90, 2018 Entomophthoromycosis, Conidiobolomycosis (Conidiobolus coronatus) Int J Surg Pathol 27:67–68, 2019; NEJM 378:e13, 2018 Herpes simplex – eczema herpeticum (Kaposi’s varicelliform eruption) Clin Dermatol 32:715–733, 2014; Arch Dis Child 60:338– 343, 1985 Epstein-Barr virus – swollen erythema of face BJD 143:1351–1353, 2000 Erysipelas/cellulitis – primary or recurrent Clin in Dermatol 38:63–78, 2020

Sinusitis, acute Laryngoscope 82:1248–1263, 1972 South American blastomycosis (paracoccidioidomycosis)

Trichinosis – acute intestinal and larval migration stages – facial edema, myalgia, diarrhea, fever, and headache Clin Inf Dis 59:1750–1756, 2014 Emerg Infect Dis 17:2194–2202, 2011; due to ingestion of bear meat MMWR 53:606–610, 2004 Trypanosomiasis, African (Trypanosoma brucei rhodesiense) – joint pain during parasitemia; fever, headache, malaise; 3–10 days after appearance of chancre; ascites and peripheral edema; facial edema and edema of hands JAAD 60:897–925, 2009 Varicella – personal observation Variola Zygomycosis, subcutaneous – Conidiobolus coronatus – lower facial edema AD 124:1392–1396, 1988; very disfiguring JAAD 30:904–908, 1994

Glanders (Burkholderia mallei) JAAD 54:559–578, 2006 Gnathostomiasis Clin Inf Dis 16:33–50, 1993

INFILTRATIVE DISEASES

Herpes zoster

Amyloidosis Cutis 61:321–324, 1998

Infectious mononucleosis JAMA 187:153–154, 1964

Crystal storage histiocytossis – intralysosomal crystals of immunoglobulin (primary and secondary intralymphatic histiocytosis) – red

Lassa fever J Infect Dis 155:445–455, 1985

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and pigmented patches of back and abdomen; livedo reticularis; upper facial swelling; associated with B-cell lymphomas and plasma cell dyscrasias JAAD 77:1145–1158, 2017 Eur J Dermatol 22:814–815, 2012; red patch of back; livedo reticularis JAAD 70:927–933, 2014 Scleromyxedema Cutis 61:321–324, 1998 Self-healing juvenile cutaneous mucinosis – red nodules of face, scalp, hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; JAAD 44:273–281, 2001; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973

INFLAMMATORY DISEASES

NEOPLASTIC DISEASES Angioimmunoblastic T-cell lymphoma Oncol Letter 11:2310–2314, 2016 Angiosarcoma AD 148:683–685, 2012; JAAD 38:310–313, 1998; JAAD 38:837–840, 1998; BJD 76:21–39, 1964; unilateral JAAD Case Rep 4:794–796, 2018 Epstein-Barr virus associated lymphoproliferative lesions BJD 151:372–380, 2004 Lymphoma – hydroa vacciniforme-like cutaneous T-cell lymphoma (Epstein-Barr virus associated lymphoproliferative disorder), Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, pitted scars, fever JAAD 81::534–540, 2019; JAAD 69:112– 119, 2013; BJD 151:372–380, 2004

Crohn's disease NEJM 373:1250, 2015; Rook, p. 3112, 1998, Sixth Edition

Kaposi's sarcoma Cutis 61:321–324, 1998; AIDS Clin Rev 261–280, 1992

Gingival swelling J Oral Maxillofac Surg 56:760–764, 1998

Keratoacanthoma, generalized eruptive, of Grzybowski BJD 142:800–803, 2000

Granulomatous cheilitis Nodular fasciitis – skin-colored nodules (tender or painful) on the head and neck, extremities, or trunk AD 137:719–721, 2001 Orofacial granulomatosis – facial edema with swelling of lips, cheeks, eyelids, forehead, mucosal tags, mucosal cobblestoning, gingivitis, oral aphthae BJD 143:1119–1121, 2000 Panniculitis Pseudotumor Coll Antropol 36(Suppl 2)143–146, 2012 Sarcoidosis JAAD 39:835–838, 1999; Heerfordt's syndrome – (uveoparotid fever) – massive facial swelling due to involvement of parotid glands NEJM 369:458, 2013

METABOLIC DISEASES Cystic fibrosis – diaper dermatitis and generalized edema AD 146:171–174, 2010 Hemophagocytic syndrome AD 128:193–200, 1992 Hereditary angioedema NEJM 359:1027–1036, 2008 Hypoalbuminemia of any cause Hypothyroidism (myxedema) NEJM 372:764, 2015; Cutis 61:321– 324, 1998 Kwashiorkor – plump appearance of face Ped Derm 16:95–102, 1999 Myxedema – personal observation Nephrogenic systemic fibrosis with superior vena cava syndrome J Drugs in Dermatol 13:615–618, 2014 Nephrotic syndrome Paroxysmal nocturnal hemoglobinuria – petechiae, ecchymoses, red plaques which become hemorrhagic bullae with necrosis; lesions occur on scalp, legs, abdomen, chest, nose, and ears; acute edema of head and face; deficiency of enzymes – decayaccelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL); somatic mutation of PIG-A gene of totipotent hematopoietic stem cells JAAD 53:1090–1092, 2005; AD 138:831–836, 2002 Porphyria – adult congenital erythropoietic porphyria BJD 148:160– 164, 2003 Pregnancy JAAD 39:835–838, 1999

Leukemia cutis Cutis 61:321–324, 1998; chronic lymphocytic leukemia; T-cell prolymphocytic leukemia – facial edema; facial purpuric plaques; petechial periorbital eruption JAAD 55:467–477, 2006; cutaneous precursor B-cell acute lymphoblastic leukemia – painful swollen red cheek JAMA Derm 149:609–614, 2013 Lymphoma – chronic facial edema; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAAD 72:21–34, 2015; J Dermatol 41:29–39, 2014; JAAD 69:112–119, 2013; adult T-cell leukemia/lymphoma – widespread papulovesicular and bullous eruptions J Drugs in Dermatol 10:1469–1471, 2011; cutaneous extranodal natural killer/T-cell lymphoma – black nasal papules; edematous cheek; red plaques of arms JAAD 70:716–723, 2014; variant of extranodal NK/T cell lymphoma, nasal type/ CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of hands, subcutaneous nodules; systemic manifestations; occurs on both sun-exposed and non-sun-­exposed skin Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998;(angiocentric CTCL of childhood (hydroa-like lymphoma) of Latin America and Asia JAAD 39:835–838, 1999; JAAD 38:574–579, 1998); angiocentric lymphoma – edema of face and neck Indian J Pathol Microbiol 34:293–295, 1991; lymphomatoid granulomatosis AD 127:1693–1698, 1991; solid facial edema associated with orbital, periorbital or retro-orbital marginal B-cell lymphoma JAAD 46:325–357, 2002; JAAD 42:872–874, 2000; cutaneous T-cell lymphoma; subcutaneous panniculitic T-cell lymphoma JAAD 50:S18–22, 2004 Metastatic adenocarcinoma JAAD 39:637–638, 1998; cervical carcinoma; erythema, edema, and telangiectasia of entire central face JAAD 56:S26–28, 2007; breast carcinoma telangiectoides – personal observation Myeloma AD 130:484, 1994

PARANEOPLASTIC DISEASES Crystal-storing histiocytosis (composed of monoclonal immunoglobulins) – facial edema AD 130:484–488, 1994; periorbital

FACIAL EDEMA

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swelling J Cut Pathol 42:136–143, 2015; Hum Pathol 27:84–87, 1996; AD 130:484–488, 1994

upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008

Necrobiotic xanthogranuloma with paraproteinemia

Carcinoid syndrome – foregut (stomach, lung, pancreas) – bright red geographic flush, sustained, with burning, lacrimation, wheezing, sweating and facial edema JAAD 55:193–208, 2006; hindgut (ileal) – patchy, violaceous, intermixed with pallor, short duration; edema, telangiectasia, cyanotic nose and face, rosacea Acta DV (Stockh) 41:264–276, 1961; hypotension, oliguria JAAD 55:193– 208, 2006

PHOTOSENSITIVITY DISEASES Hydroa vacciniforme – initial erythema and edema Ped Derm 18:71–73, 2001; hydroa vacciniforme (Epstein-Barr virus-related) – red macules progress to tender papules or vesiculopapules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of cheeks, eyelids, ears, and lips AD 142:587–595, 2006 Photoallergic drug eruption Phytophotodermatitis Polymorphous light eruption – papules, plaques, and vesicles with facial edema

PRIMARY CUTANEOUS DISEASES Acne vulgaris – central forehead, periorbital skin, cheeks Cutis 61:215–216, 1998; JAAD 22:129–130, 1990; AD 121:87–90, 1985 Contact urticaria with impaired lymphatic drainage (morbus morbihan) – facial edema and erythema of mid-third and upper face JAAD 52:595–602, 2005 Facial hemiatrophy Fat pads Kimura's disease JAAD 38:143–175, 1998 Necrolytic acral erythema – acral velvety hyperpigmented and hyperkeratotic plaques of distal dorsal feet; red palms with desquamation, erythroderma with flaccid bullae, edema and desquamation of face, onychodystrophy and onycho madesis; hepatitis C Cutis 84:301–304, 2009 Rosacea fulminans – acute pustular eruption of face BJD 163:877– 879, 2010 Solid facial edema (Morbahan’s disease) (rosacea lymphedema (solid facial edema) AD 148::1395–1398, 2012; J Dermatol 27:214–216, 2000; Cutis 61:321–324, 1998; AD 131:1069–1074, 1995 Scleredema Ped Derm 27:315–317, 2010; J Pediatr 101:960–963, 1982

DRESS syndrome – drug reaction with eosinophilia and systemic symptoms – facial edema, exfoliative dermatitis, follicular eruptions; association with HHV-6; lymphadenopathy, circulating atypical lymphocytes, abnormal liver function tests AD 137:301–304, 2001; Semin Cutan Med Surg 15:250–257, 1996 Facial edema with eosinophilia (non-episodic angioedema with eosinophilia) Case Rep Dermatol 12:164–168, 2017 Facial hemihypertrophy Generalized lymphedema associated with neurologic signs – facial edema JAAD 72:333–339, 2015 Hemophagocytic lymphohistiocytosis – personal observation Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, hirsutism, bilateral single palmar crease, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia JAAD 56:353–370, 2007; Ped Derm 23:239–242, 2006; Am J Med Genet 34:593–600, 1989 Hereditary angioneurotic edema – C1 esterase inhibitor deficiency (inherited, acquired, dysfunctional) serpiginous erythema; triad of circumscribed edema of the skin, laryngeal edema, and abdominal pain JAAD 65:843–850, 2011; BJD 161:1153–1158, 2009; J Invest Allergol Clin Immunol 2:318–322, 1992; Hosp TID No.40.1 rk 4:741–747, 1886; Monatsschr Prakt Dermatol 1:129–131, 1882; Edinb Med J 22:513–526, 1876 Hurler’s syndrome (mucopolysaccharidosis Cutis 61:321–324, 1998 Infantile cortical hyperostosis Cutis 61:321–324, 1998 McCune-Albright syndrome Cutis 61:321–324, 1998

Urticaria multiforme – annular, serpiginous, urticarial lesions; edema of hands, feet, face NEJM 375:470, 2016

Melkersson-Rosenthal syndrome (orofacial granulomatosis) – orofacial edema; edema of cheeks, forehead, eyelids, scalp AD 144:1627–1630, 2008; BJD 143:860–863, 2000; Oral Surg Oral Med Oral Pathol 75:220–224, 1993; Oral Surg Oral Med Oral Pathol 74:610–619, 1992; JAAD 21:1263–1270, 1989; Oral Surg Oral Med Oral Pathol 54:404–413, 1982

PSYCHOCUTANEOUS DISORDERS

Neurofibromatosis – plexiform neurofibroma

Factitial lymphedema – personal observation

Self-healing juvenile cutaneous mucinosis AD 131:495–461, 1995

SYNDROMES

Sphenopalatine syndrome – chronic and intermittent edema of face with unilateral lacrimation, rhinitis, erythema of the bridge of the nose

Solid facial edema – personal observation

Antiphospholipid antibody syndrome – with superior vena cava syndrome J Rheumatol 18:95–97, 1991 Apert's syndrome Cutis 61:321–324, 1998 Ascher's syndrome Behcet’s syndrome – superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of neck with neck vein distension,

Williams’ syndrome – malar puffiness Ped 80:85–91, 1987

TOXINS Arsenic poisoning – acute BJD 149:757–762, 2003 Potato poisoning – rash of lower abdomen and medial thighs consisting of red papules which progress to pustules and crusted

382 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 lesions; facial and abdominal edema; headache, vomiting, diarrhea J R Coll Physicians Edinb 36:336–339, 2007

TRAUMA Asphyxia – facial congestion, facial edema, cyanosis, periorbital or conjunctival petechiae JAAD 64:811–824, 2011 Cold urticaria Anesthesiology 90:907–909, 1999 Coma bullae – facial bullae with edema Cutis 69:265–268, 2002 Dental treatment – soft tissue cervicofacial emphysema after dental treatment AD 141:1437–1440, 2005 Post-surgical (face lift) Plast Reconstr Surg 98:1–6, 1996 Prone posturing in acute respiratory distress syndrome; Covid-19 pneumonia Arch Acad Emerg Med 8:e48, 2020; Am J Resp Crit Care Med 165:1359–1363, 2002 Radiation of tongue for squamous cell carcinoma – personal observation Root canal surgery AD 132:231–233, 1996 Subcutaneous emphysema AD 134:557–559, 1998

PHACES syndrome – large facial hemangioma with hemifacial enlargement Curr Prob in Dermatol 13:249–300, 2002 Septic facial vein thrombosis (Staphylococcus aureus) AD 145:1460–1461, 2009 Sturge-Weber syndrome Cutis 61:321–324, 1998 Superior vena cava syndrome – bronchogenic cancer, lymphoma, breast cancer, malignant thymoma, seminoma, mediastinal fibrosis, thrombosis, inflammatory lymph nodes, retrosternal goiter, aortic aneurysm Cutis 79:362, 367–368, 2007; Cutis 77:305–309, 2006; Pediatr Hematol Oncol 18:71–77, 2001; Am Rev Respir Dis 141:1114–1118, 1990; Mayo Clinic Proc 56:407–413, 1981; Behcet’s disease J Vasc Surg 41:548–551, 2005; metastatic neuroendocrine carcinoma to mediastinum – facial swelling Postgrad Med J 65:327–328, 1989; metastatic neuroendocrine carcinoma to mediastinum – facial edema and telangiectasia JAMADerm 151:562–564, 2015; syphilitic aortic aneurysm Med Obst Soc Phys (London) 1:323–357, 1757; substernal goiter, thrombosis or fibrosis of central venous catheters, pacemaker wires, fibrosing mediastinitis, aortic aneurysms JAAD 77:391–402, 2017; Behcet’s disease Acta Clin Belg 74:364–359, 2019 Vasculitis – edematous scarring vasculitic panniculitis JAAD 32:37–44, 1995

VASCULAR DISEASES Acute hemorrhagic edema of infancy – edema of face and extremities JAAD 59:684–695, 2008 Anasarca Angiolymphoid hyperplasia with eosinophilia Ped Derm 15: 91–96, 1998 Angiosarcoma of face and scalp (facial edema at beginning of development) JAAD 38:143–175, 1998; Cancer 59:1046–1057, 1987; facial edema and violaceous plaque covering entire cheek AD 143:1602–1603, 2007 Capillary leak syndrome Ann Int Med 130:905–909, 1999 Eosinophilic granulomatosis with polyangiitis JAAD 47:209–216, 2002; JAAD 39:835–838, 1999; JAAD 37:199– 203, 1997 Constrictive pericarditis Eosinophilic vasculitis syndrome (recurrent cutaneous necrotizing eosinophilic vasculitis) BJD 149:901–902, 2003; Sem Derm 14:106–110, 1995 Giant cell arteritis Rev Rhum Engl Ed 63:145–147, 1996

FACIAL PAPULES AND PLAQUES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – dermal contact dermatitis to bovine collagen Chronic granulomatous disease – DLE-like plaque AD 126: 1656–1658, 1990; X-linked chronic granulomatous disease – DLElike lesions and stomatitis in female carriers BJD 104:495–505, 1981 Chronic urticaria Immunodeficiency disease with RAG mutations and granulomas – papulonodular lesions of face NEJM 358:2030–2038, 2008 Still’s disease Semin Arth Rheum 42:317–326, 2012 Systemic lupus erythematosus – photosensitivity, chilblain lupus of fingertips and toes, rosacea-like lesions of face, lupus profundus, red plaques, stomatitis Ped Derm 3:376–379, 1986; mucinosis Medicine 96:e8391, 2017

Granulomatosis with polyangiitis Hemangiomas – hemangioma beyond proliferative stage – hypertrophy of lip, chin, and neck Ped Derm 28:94–98, 2011 Henoch-Schonlein purpura – scalp and facial edema preceding HSP Ped Derm 9:311, 1992; eyelid and facial edema due to intracerebral hemorrhage Brain and Development 24:115–117, 2002 Kasabach-Merritt syndrome – swollen face and neck with deep red infiltrated tumor; Kaposiform hemangioendothelioma Ped Derm 31:595–598, 2014 Lemierre’s syndrome – swollen red eyelid; due to Fusobacterium necrophorum; cavernous sinus thrombophlebitis, carotid artery thromboarteritis, abscess of parotid gland and subperiosteal orbit NEJM 371:2018–2027, 2014 Lymphangiosarcoma – edema of cheek JAAD 56:530–531, 2007 Lymphedema – congenital (Milroy’s disease) Rook, pp. 2283, 2289, 1998, Sixth Edition; lymphedema tarda – personal observation

CONGENITAL LESIONS Preauricular tags and fistulae   Cat eye syndrome   Chromosome 4p- syndrome   Chromosome 5p- syndrome   Trisomy 9

DRUG-INDUCED Angiofibroma-like papules of the chin induced by cyclosporine AD 129:794–795, 1993 Chlorpromazine lupus-like rash JAAD 13:109–115, 1985 Collagen, injectable – granulomatous reaction to injectable collagen Cutis 51:95–98, 1993 Corticosteroid acne – oral, topical, inhaled

Facial Papules and Plaques Internal/external drug reaction – Kanamycin

Toxoplasmosis in AIDS AD 124:1446–1447, 1988

MESNA drug reaction mimicking worsening SLE AD 128:80–82, 1992

Verrucae vulgaris JAAD 55:533–535, 2006

Methotrexate-associated lymphoproliferative disorder – red papules and plaques of nose, cheeks, eyelids JAAD 56:686–690, 2007 Pseudolymphoma, drug induced – anticonvulsants captopril, enalapril J Clin Pathol 39:902–907, 1986; atenolol Clin Exp Dermatol 115:119–120, 1990; ACE-inhibitors, amitryptiline Curr Probl Dermatol 19:176–182, 1990 Systemic 5-FU inflaming actinic keratoses

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INFILTRATIVE DISEASES Alopecia mucinosa An Bras Dermatol 90(Suppl 1)147–149, 2015; Indian Dermatol J Online 4:333–335, 2013 Amyloidosis – primary systemic amyloidosis An Bras Dermatol 87:119–122, 2012 Benign reactive follicular mucinosis – red papules and plaques of face Cutis 89:266–268, 2012

EXOGENOUS AGENTS

Colloid milium Ped Derm 33:e201–203, 2016; Clin Exp Dermatol 34:745–746, 2009

Bromoderma – single or multiple papillomatous nodules and/or plaques studded with pustules on face or extremities Ped Derm 18:336–338, 2001; AD 115:1334–1335, 1979

Jessner's lymphocytic AD 124:1091–1093, 1988 Juvenile xanthogranulomas, multiple AD 125:1703–1708, 1989 Langerhans cell histiocytosis Ped Derm 35:827–828, 2018

INFECTIONS AND INFESTATIONS

Lymphocytoma cutis; Cancer 69:717–724, 1992; Acta DV (Stockh)62:119–124, 1982

Alternariosis AD 124:1822–1825, 1988

Non-X histiocytosis JAAD 13:645–649, 1985

Anthrax – Bacillus anthracis; malignant pustule; face, neck, hands, arms; starts as papule then evolves into bulla on red base; then hemorrhagic crust with edema and erythema with small vesicles; edema of surrounding skin Br J Opthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355– 361, 1981

Pseudolymphoma Scleromyxedema Am J Dermatopathol 41:505–510, 2019 Sea blue histiocytosis – facial macular brown hyperpigmentation; nodules of face, trunk, hands, and feet; eyelid infiltration; puffy face; leonine facies JAAD 57:1031–1045, 2007

Chromomycosis JAAD 44:585–592, 2001

Self-healing juvenile cutaneous mucinosis – papules, plaques, and nodules of head and trunk JAAD 31:815–816, 1994

Coccidioidomycosis Dermatol Online J 16:6, 2010’ AD 123:937– 942, 1987

Urticating Langerhans cell histiocytosis JAAD 14:867–873, 1986

Cryptococcosis Mycopathologia 161:235–238, 2006 Demodicidosis in childhood ALL – perioral, annular, serpiginous papules

Xanthoma disseminatum – intertriginous violaceous-yellow purpuric papules, confluent xanthomatous plaques in axillae, groin, other folds; face, eyelids, chest upper back, globe of eyeball AD 147:459– 464, 2011; JAAD 23:63–67, 1990

Dermatophytosis – tinea faciei; tinea incognito Epidermodysplasia verruciformis Ped Derm Oct 23, 2019; Int J Dermatol 47:476–478, 2008

INFLAMMATORY DERMATOSES

Histoplasmosis Clin Exp Dermatol 34:481–486, 2009

Crohn’s disease – metastatic Crohn's disease AD 129:1348–1351, 1993

Leishmaniasis recidivans Cutis 37:177–179, 1986; chronic lupoid leishmaniasis; L. aethiopica; post kala-azar leishmaniasis Leprosy, including erythema nodosum leprosum; histoid leprosy AD 140:751–756, 2004; Int J Lepr Other Mycobact Dis 68:272–276, 2000; Int J Lepr 31:608–609, 1963; Int J Lepr 28:469, 1960; histoid leprosy – centrofacial distribution BJD 160:305–310, 2009 Lupoid sycosis Int J Dermatol 26:539–540, 1987 Mycobacterium africanum (TB) Clin Inf Dis 21:653–655, 1995 Mycobacterium marinum – disseminated infection Cutis 36:405– 408, 1985

Eosinophilic pustular folliculitis JAAD 29:259–260, 1993; Ofuji's disease JAAD 37:259–261, 1999 Kikuchi's histiocytic necrotizing lymphadenitis with cutaneous involvement – red papules of face, back, arms; red plaques; erythema and acneform lesions of face; morbilliform, urticarial, and rubella-like exanthems; red or ulcerated pharynx; cervical adenopathy; associations with SLE, lymphoma, tuberculous adenitis, viral lymphadenitis, infectious mononucleosis, and drug eruptions BJD 144:885–889, 2001; Ped Derm 18:403–405, 2001; JAAD 36:342– 346, 1996; Am J Surg Pathol 14:872–876, 1990

North American blastomycosis JAAD Case Rep 5:834, 2019; J Emerg Med 54:e11–12, 2018

Malignant pyoderma (cephalic granulomatosis with polyangiitis) – papulopustules, skin ulcers, violaceous nodules with central necrosis, tongue, pharyngeal, and nasal ulcers AD 146:102–103, 2010; AD 98:561–576, 1968

Paracoccidioidomycosis (Paracoccidioides brasiliensis) JAAD 53:931–951, 2005; Cutis 40:214–216, 1987

Neutrophilic eccrine hidradenitis – red/purple papules and plaques AD 139:531–536, 2003

Sporotrichosis Dermatol Online J Nov 15, 2018

Neutrophilic sebaceous adenitis AD 129:910–911, 1993

Syphilis – secondary syphilis (papulonodular syphilis), malignant syphilis NEJM 368:561, 2013; AD 123:1707–1712, 1987; nodular secondary syphilis AD 144:1078–1079, 2008

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – facial papules and nodules, purple plaques JAAD 51:931–939, 2004; Semin Diagn Pathol 7:19–73, 1990

Mycobacterium tuberculosis – lupus vulgaris JAAD 26:404–407, 1992

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Sarcoid AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; Clinics in Chest Medicine 18:663–679, 1997

Melanoma Semin Oncol 2:5–118, 1975

Stevens-Johnson syndrome – personal observation

Metastases – medulloblastoma; deep red plaque/tumor BJD 154:554–555, 2006

METABOLIC Acromegaly Erythropoietic protoporphyria BJD 17:412–414, 2014

Merkel cell carcinoma

Microcystic adnexal carcinoma Dermatol Ther 21:452–458, 2008; JAAD 29:840–845, 1993 Multinucleated cell angiohistiocytoma J Dermatol Case Rep 10:58–61, 2016

Farber's disease (ceramidase deficiency) – subcutaneous nodules, hoarse voice, joint contractures Orphanet J Rare Dis 13:121, 2018

Multiple myeloma AD 139:475–486, 2003

Pruritic urticarial papules and plaques of pregnancy (PUPPP) JAAD 17:302, 1987

Palisaded encapsulated neuromas AD 125:386–389, 1989

NEOPLASTIC

Post- transplant lymphoproliferative disorder – facial nodules and violaceous macules Ped Derm 36:681–685, 2019

Atypical fibroxanthoma Dermatol Ther 21:424–427, 2008 Basal cell carcinoma, including nevoid basal cell carcinoma syndrome (Gorlin’s syndrome)

Rhabdomyosarcoma in neonates and children (nodules) – facial nodules with plaques Dermatol Therapy 18:104–116, 2005; JAAD 30:243–249, 1994

Basaloid follicular hamartoma (yellow plaque with milia) AD

Schwannomatosis AD 125:390–393, 1989

129:915–917, 1993; unilateral linear Indian Dermatol Online J 10:710–713, 2019

Syringomas

Benign cephalic histiocytosis AD 122:1038–1043, 1986; JAAD 13:383–404, 1985;

Trichoepithelioma, desmoplastic

Nevus sebaceus Plasmacytosis Indian J DV Leprol 83:673–676, 2017; Oncol Letter 11:1923–1925, 2016

Trichoblastic fibroma AD 131:198, 1995

Clear cell acanthomas Indian J Dermatol 58:162, 2013 Collagenomas, eruptive Indian J Dermatol 60:104, 2015

PARANEOPLASTIC

Eccrine angiomatous nevus JAAD 29:274–275, 1993

Platelet plugging with associated myeloproliferative disease – red papules and plaques JAAD 43:355–357, 2000

Epidermal nevus Familial multiple eccrine spiradenomas with trichoepitheliomas Cutis 46:46–50, 1990 Follicular hamartoma JAAD 39:853–857, 1998; Clin Exp Dermatol 6:283–289, 1981

PHOTODERMATITIS Actinic prurigo – cheilitis Am J Dermatopathol 38:418–422, 2016

Generalized eruptive histiocytomas

Actinic reticuloid JAAD 21:205–214, 1989

Hair follicle nevus (hair follicle hamartoma) – pedunculated papule or nodule Ped Derm 13:135–138, 1996

Polymorphic light eruption Adv Exp Med Biol 996:61–70, 2017

Kaposi’s sarcoma JAAD 38:143–175, 1998; Int J Derm 36:735–740, 1997; Dermatology 190:324–326, 1995 Keloids

PRIMARY CUTANEOUS DISEASES

Leiomyomas Cutis 73:335–337, 2004

Angiolymphoid hyperplasia with eosinophilia Dermatopathol (Basel)6:225–230, 2019; JAAD 12:781–796, 1985

Lentigo maligna melanoma

Darier's disease Case Rep Dermatol 11:327–333, 2019

Leukemia cutis, including chloroma (granulocytic sarcoma) Cutis 34:285–287, 1984; neonatal aleukemic leukemia cutis; HTLV-1 T-cell leukemia/lymphoma – red-brown papules and plaques Ped Derm 25:373–377, 2008; aleukemic leukemia cutis, ALL Indian J Hematol Blood Transfus 32(suppl 1)46–49, 2016

Elastosis perforans serpiginosa J Cut Med Surg 14:38–42, 2010; AD 145:931–936, 2009

Lymphoma – Hodgkin's disease – ulcerated papules, plaques, and nodules of the faces and scalp and face AD 127:405, 408, 1991; Cutis 32:79–82, 1983; cutaneous T-cell lymphoma; lymphomatoid granulomatosis (angiocentric lymphoma) JAAD 27:872–876, 1992; CD56+ lymphoma BJD 147:1017–1020, 2000; primary cutaneous B-cell lymphoma JAAD 53:479–484, 2005; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 69:112–119, 2013 Lymphomatoid papulosis Acta DV Croat 26:264–266, 2018 Mastocytosis

Eosinophilic pustular folliculitis – sterile papules, pustules, and plaques of face, trunk, arms, palms, soles JAAD 23:1012–1014, 1990; JAAD 14:469–474, 1986 Epidermodysplasia verruciformis-like eruption – personal observation Erythema elevatum diutinum Cutis 53:124–126, 1994 Granuloma annulare, disseminated; periocular granuloma annulare Ped Derm 31:722–725, 2014 Granuloma faciale JAAD 51:269–273, 2004 Granulomatous perioral dermatitis Keratosis lichenoides chronica – resembling seborrheic dermatitis or acne rosacea J Dermatol Treat 27:383–388, 2016; JAAD 28:870–873, 1993; Ped Derm 11:46–48, 1994 Lichen myxedematosus – personal observation

Facial Papules Mid-dermal elastolysis (plaque resembling eosinophilic pustular folliculitis) JAAD 28:938–942, 1993 Ofuji’s disease – red plaque with papules and pustules JAAD 46:827–833, 2002 Parapsoriasis – large plaque parapsoriasis Perioral dermatitis

TRAUMA Scar

VASCULAR

Pityriasis rosea

Acute hemorrhagic edema of infancy (Seidlmayer’s syndrome) Blood Res 8:1771, 2019

Transient acantholytic acanthosis Cutis 38:48–49, 1986

Angiosarcoma

X-linked ectoderma dysplasia Hautarzt 42:645–647, 1991

Eosinophilic granulomatosis with polyangiitis – necrotic eschar within red plaque; red papules of forehead and scalp JAAD 65:244–246, 2011

PSYCHOCUTANEOUS DISEASE

Glomangioma – hemi-facial JAAD 45:239–245, 2001

Factitial dermatitis JAAD 76:779–791, 2017

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Granulomatosis with polyangiitis BJD 155:221–222, 2008 Henoch-Schonlein purpura Microscopic polyarteritis nodosa

SYNDROMES

Takayasu's arteritis – LE-like rash Circulation 35:1141–1155, 1967

Anhidrotic ectodermal dysplasia

Tufted angioma – violaceous nodule; rarely multiple painful eruptive Indian J Dermatol 46:412–414, 2011

Bannayan-Riley-Ruvalcaba syndrome – trichilemmomas and verrucae AD 132:1214–1218, 1996

Vasculitis

Bazex syndrome Cowden's syndrome Dermochondrocorneal dystrophy AD 124:424–428, 1988 Goltz's syndrome Hyaline fibromatosis Indian J Dermatol 6:580, 2010 Lipoid proteinosis – hoarseness in infancy, waxy papules and plaques of face and body; pock-like and acneiform scars, beaded eyelid margins Ped Derm 9:264–267, 1992 Multicentric reticulohistiocytosis – yellow papules and plaques Cutis 85:153–155, 2010; BJD 161:470–472, 2009; AD 144:1383– 1388, 2008; AD 144:1360–1366, 2008; AD 144:105–110, 2008; JAAD 58:541–543, 2008; JAAD 56:302–316, 2007; JAAD 53:1075– 1079, 2005; AD 140:919–921, 2004; JAAD 49:1125–1127, 2003; JAAD 25:948–951, 1991; AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; Clin Exp Dermatol 5:267–279, 1980; AD 97:543–547, 1968 Multiple mucosal neuroma syndrome (MEN II) Neurofibromatosis Pachydermoperiostosis Pachyonychia congenita – follicular papules of face Indian Dermatol Online J 7:278–280, 2016 Rombo syndrome Rosai-Dorfman syndrome BJD 148:1060–1061, 2003 Sweet’s syndrome JAAD 49:132–138, 2003; chronic recurrent Sweet’s syndrome of myelodysplasia – pustules, plaques, and papules AD 142:1170–1176, 2006 Tuberous sclerosis Ped Neurol 49:243–254, 2013 Wells' syndrome AD 142:1157–1161, 2006; AD 125:1625–1626, 1989

TOXIN Foreign body granuloma Ragweed contact dermatitis

FACIAL PAPULES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Adult and juvenile Still’s disease – palmoplantar vesiculopustular eruption with fixed facial papules J Korean Med Sci 17:852–855, 2002 Allergic contact dermatitis – granulomatous allergic contact dermatitis due to topical propolis BJD 144:1277–1278, 2001 Bowel-associated dermatitis-arthritis syndrome AD 135:1409–1414, 1999 Chronic granulomatous disease – translucent facial papules around eyes, nose, lips, cheeks; mimics lupus vulgaris NEJM 317:687–694, 1987 Dermatitis herpetiformis Dermatologica 155:350–354, 1977 GATA 2 deficiency – granulomatous facial papules BJD 178:781– 785, 2018 Graft vs. host disease, pediatric – red macules or folliculocentric papules of face, ears, palms and soles, periungual areas, upper back and neck AD 143:67–71, 2007 Hyper IgE syndrome – papulopustules of face and scalp in first year of life J Pediatr 141:572–575, 2003; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983 Lupus erythematosus – arteritis, lupus profundus JAAD 16:839– 844, 1987, discoid lupus, systemic lupus; chilblain lupus – red papules of face, nose Cutis 69:183–184, 190, 2002; tumid lupus; mucinosis Urticaria

CONGENITAL Accessory tragus – facial, glabellar papule – isolated Cutis 88:62–64, 2011; accessory tragus at nasal vestibule in nasal rim Ped Derm 37:383–384, 2020

386 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Accessory tragi Cutis 88:62–64, 2011; JAAD 50:S11–13, 2004

Dermoid cyst (midline) Pediatr Rev 11(9):262–267, 1990

Delleman syndrome – autosomal dominant with variable penetrance, multiple craniofacial skin tags, striated muscle hamartomas, orbital cysts (exophthalmia or microthalmia), cerebral malformations, periorbital or postauricular appendages, focal dermal hypoplasia and aplasia (aplasia cutis congenita), rib defects, psychomotor retardation, seizures, skull defects; no ear abnormalities Clin Genet 19:191–198, 1981

Encephalocoele – blue nodule Pediatr Rev 11(9):262–267, 1990; anterior encephalocele – facial nodule JAAD 51:577–579, 2004

Encephalocraniocutaneous lipomatosis (Haberland syndrome) – also has nevus psiloliparus (hairy fatty nevus) Goldenhaar syndrome – (oculo-auriculo-vertebral syndrome) – autosomal recessive; macroglossia, preauricular tags, abnormal pinnae, facial asymmetry, macrostomia, epibulbar dermoids or lipodermoids, auricular fistula, deafness, facial weakness, central nervous system, renal, and skeletal anomalies),

Lacrimal duct cyst Meningocoele Microcystic adnexal carcinoma AD 147:256–257, 2011 Nasal glioma – blue or red nodule J Neurosurg 64:516–519. 1986; Pediatr Rev 11(9):262–267, 1990; papule of nose AD 137:1095– 1100, 2001 Neuroblastoma Rhabdomyosarcoma Sebaceous hyperplasias of the nose

Nagers syndrome

Striated muscle hamartoma (rhabdomyomatous mesenchymal hamartoma) – skin colored papules of central face; may be single or multiple, dome-shaped, pedunculated or filiform Ped Derm 16:65–67, 1999

Otomandibular dysostosis

Systemic hyalinosis

Treacher-Collins syndrome (mandibulofacial dysostosis) – autosomal dominant; auricular defects, malar hypoplasia, down-slanting palpebral fissures, lower eyelid defects

DRUG-INDUCED

Hurson syndrome

Townes-Brocks syndrome – autosomal dominant; external ear malformations, polydactyly, renal and anal malformations Am J Med Genet 18:147–152, 1984 VACTERL syndrome (vertebral anomalies, anorectal malformations, cardiac defects, tracheo-esophageal fistulae, renal or radial anomalies, limb malformations) – sporadic J Pediatr 93:270–273, 1978 Wolf-Hirschhorn (4p deletion) syndrome (oculocerebrocutaneous syndrome) – growth and mental retardation with seizures, microcephaly, hypospadius, cryptorchidism, facial and ear abnormalities, down-turned mouth with cleft lip and/or palate and short philtrum Ped Derm 17:391–394, 2000 Differential diagnosis of accessory tragus includes:  Acrochordon   Adnexal tumor   Auricular fistula   Branchial cleft cyst and/or fistula   Cartilaginous remnants   Congenital midline hamartoma   Epidermoid cyst   Hair follicle nevus  Lipoma   Skin tags   Thyroglossal duct cyst  Wattle Angiomatous nevus Blueberry muffin baby NEJM 362:833, 2010 Branchial cleft cyst – first branchial remnants; mass or sinus tract anterior and inferior to ear or parotid Ped Clin North Amer 6:1151– 1160, 1993 Bronchogenic cyst – skin-colored nodule of chin BJD 143:1353– 1355, 2000 Chin hamartoma – multipapillated yellow-pink papules of chin with underlying infantile hemangioma; biopsy demonstrates sebaceous hamartoma of dermal fibroplasia with prominent vessels Ped Derm 37:78–85, 2020 Congenital midline hamartoma – polypoid nodule of chin Ped Derm 7:199–201, 1990 Congenital vellus hamartoma (hair follicle nevus) – skin colored papule of face Int J Dermatol 31:578–581, 1992

BCG vaccination, disseminated – umbilicated facial papules Ped Derm 18:205–209, 2001;Ped Derm 13:451–454, 1996 Bromoderma Capecitabine – inflammation of actinic keratosis Carboplatin and docetaxel – inflammation of actinic keratosis Cases Journal 9:6946–6948, 2009 Collagen implants – granulomatous reaction Cutis 51:95–98, 1993 Corticosteroids – steroid acne; steroid perioral dermatitis Cyclosporine – lymphocytic infiltrate JAAD 23:1137–1141, 1990; cyclosporine-induced folliculodystrophy (viral associated trichodysplasia) JAAD 50:318–322, 2004 – cobblestoned follicular facial papules JAAD 50:310–315, 2004; sebaceous gland hyperplasia BJD 149:198–200, 2003; JAAD 35:696–699, 1996; Dermatologica 172:24–30, 1986; papules of chin – lymphocytic infiltrate AD 129:794–795, 1993 Drug rash Erbitux (cetuximab) (epidermal growth factor receptor inhibitor) 5-fluorouracil, systemic, – inflamed actinic keratoses Imatinib – eccrine squamous syringometaplasia; red facial papules JAAD 55:S58–59, 2006 Methylphenidate hydrochloride – lymphomatoid drug reaction; facial papulonodules Cutis 81:61–64, 2008 Pseudolymphoma, drug induced – anticonvulsants; captopril, enalapril J Clin Pathol 39:902–907, 1986; atenolol Clin Exp Dermatol 115:119–120, 1990; ACE-inhibitors, amitryptiline Curr Probl Dermatol 19:176–182, 1990 Trametinib – xanthogranulomas Cutis 102:283–286, 2018 Vemurafinib – multiple nodules of cheeks; follicular plugging; exuberant seborrheic dermatitis-like hyperkeratosis of face; hand and foot reaction; diffuse spiny follicular hyperkeratosis; cobblestoning of forehead JAAD 67:1375–1379, 2012

EXOGENOUS AGENTS Foreign body granuloma (to bindi) AD 127:424, 1991 Hyaluronic acid (Captique) – hypersensitivity reaction to non-animal stabilized hyaluronic acid; facial nodules Cutis 79:388–389, 2007; JAAD 55:128–131, 2006

Facial Papules

387

Iododerma Australas J Dermatol 29:179–180, 1988

Eosinophilic folliculitis of HIV disease

Irritant contact dermatitis

Epidermodysplasia verruciformis BJD 121:463–469, 1989; Arch Dermatol Res 278:153–160, 1985; acquired epidermodysplasia verruciformis of HIV – flat topped papules of hand, forehead, scalp AD 146:903–905, 2010; demodex-associated spinulosis – sandpaper face JAMADerm 151:1251–1252, 2015

Ochronosis – exogenous ochronosis JAAD 39:527–544, 1998 Silicone – silicone granulomas with facial nodules at crow’s feet BJD 152:1064–1065, 2005; metastatic silicone granuloma AD 138:537– 538, 2002 Tooth – extruding tooth; white papule Cutis 54:253–254, 1994

INFECTIOUS Acremonium sepsis JAAD 37:1006–1008, 1997 Actinomycosis, cervicofacial Laryngoscope 94:1198–1217, 1984 Adenovirus, disseminated in stem cell transplant BJD 174:885–888, 2016

Filariasis (Brugia) – multiple nodules of forehead and scalp Ped Derm 25:230–232, 2008 Fusarium sepsis facial papules; sinopulmonary infections JAAD 75:19–30, 2016; JAAD 37:1006–1008, 1997 Gianotti-Crosti syndrome – papular acrodermatitis of childhood; papules of buttocks and thighs, then extensor arms, then face JAAD 65:876–877, 2011; JAAD 54:136–145, 2006; JAAD 26:207–210, 1992; AD 124:1705–1710, 1988; AD 120:891–896, 1984 Hand, foot, and mouth disease -

African histoplasmosis

enterovirus Ann Dermatol 24:200–202, 2012

Anthrax – Bacillus anthracis; malignant pustule; face, neck, hands, arms; starts as papule then evolves into bulla on red base; then hemorrhagic crust with edema and erythema with small vesicles; edema of surrounding skin Br J Opthalmol 76:753–754, 1992; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355– 361, 1981

Herpes simples Perm J May 31, 2019

Bacillary angiomatosis – Bartonella henselae BJD 143:609–611, 2000; AD 131:933–936, 1995 Bartonellosis (Bartonella bacilliformis) – mular lesions; 1–4 mm pruritic red papules Clin Inf Dis 33:772–779, 2001; Oroya fever with verruga peruana; red papules in crops become nodular, hemangiomatous or pedunculated; face, neck, extremities, mucosal lesions JAAD 47:641–655, 2002; Ann Rev Microbiol 35:325–338, 1981 Bejel Botryomycosis Cutis 80:45–47, 2007 Candida tropicalis sepsis – personal observation Cercarial dermatitis (swimmer’s itch) – facial papules JAAD 60:174–176, 2009 Chromomycosis – feet, legs, arms, face, and neck AD 133:1027– 1032, 1997; BJD 96:454–458, 1977; AD 104:476–485, 1971 Coccidioidomycosis – ulcerated frambesiform papules of face JAAD 55:929–942, 2006 Coxsackie A16 – Gianotti-Crosti-like rash JAAD 6:862–866, 1982 Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of fingers, palmar erythema, red papules of ears, red papules of antecubital fossa, perioral papulovesicles, vesicles of posterior pharynx; crusted papules of scalp, ears, and face; purpuric targetoid painful vesicular lesions of hands and feet, arthritis, fissured scrotum JAMA Derm 149:1419–1421, 2013; JAAD 69:736–741, 2013 Cryptococcosis – papules, umbilicated papules, pseudofolliculitislike lesions Cutis 66:337–340, 2000 Cytomegalovirus, congenital – blueberry muffin (violaceousmagenta macules) baby (extramedullary hematopoiesis) NEJM 362, 833, 2010 Demodicidosis – rosacea-like papules – cheeks, periorally, nose JAAD 77:221–230, 2017; Ped Derm 20:28–30, 2003; BJD 144:139– 142, 2001; papular facial dermatitis in children with acute lymphoblastic leukemia Ped Derm 22:407–411, 2005; hyperkeratotic papules of face Ped Derm 33:671–672, 2016; AD 151:1251–1252, 2015

Herpes zoster – verrucous follicular papules of face in patient with B-cell lymphoma AD 148:405, 2012 Histoplasmosis in HIV disease – red facial papules Clin in Dermatol 38:52–62, 2020; Cutis 80:309–312, 2007; Cutis 72:439–445, 2003; umbilicated facial papules Cutis 91:291–294, 2013; facial papules, crusted papules, muscle weakness, pulmonary infiltrates; morbilliform rash with scale BJD 173:797–800, 2015 Leishmaniasis AD 134:193–198, 1998; L. tropica – ulcerated nodule of face JAAD 53:810–815, 2005; post-kala azar dermal leishmaniasis (L donovani, L. Infantum, L.chagasi); erythema and induration of butterfly region with hypopigmented macules of trunk and extremities; and infiltrated papules and nodules of forehead, chin, and central face JAAD 73:911–926, 2015; BJD 157:811–813, 2007; BJD 143:136–143, 2000; JAAD 34:257, 1996 Leprosy – lepromatous – skin colored facial papules Ped Derm 32:863–864, 2015; erythema nodosum leprosum; histoid leprosy AD 140:751–756, 2004; Int J Lepr Other Mycobact Dis 68:272–276, 2000; Int J Lepr 31:608–609, 1963; Int J Lepr 28:469, 1960 Molluscum contagiosum BJD 115:131–138, 1987 Mycetoma – facial nodule (nocardia) JAAD 49:S170–173, 2003 Mycobacteria, non-tuberculous – infections following cosmetic laser procedures J Drugs Dermatol 14:80–83, 2015 Mycobacterium chelonae – facial lesions; red papules and nodules BJD 170:471–473, 2014; red papules following cosmetic laser procedure J Drugs Dermatol 14:80–83, 2015 Mycobacterium haemophilum AD 138:229–230, 2002 Mycobacterium marinum, disseminated Cutis 36:405–408, 1985; facial J Pediatr 130:324–326, 1997; AD 122:698–703, 1986 Mycobacterium shigaense Emerging Inf Dis 19:819–820, 2013 Mycobacterium tuberculosis – papulonecrotic tuberculid – dusky red crusted or ulcerated papules occur in crops on elbows, hands, feet, knees, legs; also ears, face, buttock, and penis Ped Derm 15:450– 455, 1998; Int J Dermatol 30:487–490, 1991; Ped Derm 7:191–195, 1990; lupus vulgaris; miliary tuberculosis JAAD 50:S110–113, 2004 Myiasis Clin Microbiol Infect 23:542–543, 2017 North American blastomycosis AD 136:547–550, 2000 Papular dermatitis of HIV (pruritic papular eruption of HIV) Dermatol Clin 24:449–457, 2006

Dermatophytosis – personal observation

Paracoccidioidomycosis – facial, oral and perioral lesions Clin in Dermatol 38:52–62, 2020; JAAD 53:931–951, 2005

Dental sinus – facial nodule Ped Derm 29:421–425, 2012; Cutis 70:264–267, 2002

Talaromyces (Penicillium) marneffei Indian J Dermatol 64:331–332, 2019; NEJM 344:1763, 2001; Clin Inf Dis 18:246–247, 1994

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Rat bite fever (Streptobacillus moniliformis) – fever, arthritis, exanthema; papules and papulopustules of face and hand; hand and foot swellings Ped Derm 29:767–768, 2012 Rhinosporidiosis Ear Nose Throat 97:E15–17, 2018 Rickettsial pox – personal observation Scabies – crusted papules BJD 126:523–524, 1990 Schistosomiasis BJD 119:793–8, 1988 Sporotrichosis – secondary to cat scratch; periorbital papules Ped Derm 28:457–458, 2011; AD 118:429–431, 1982; disseminated in HIV disease Case Rep Inf Dis 2017:4713140 Sycosis barbae Sycosis vulgaris Syphilis – secondary – morbilliform or papular (copper red) J Clin Inf Dis 21:1361–1371, 1995; tertiary AD 123:1707–1712, 1987; corona veneris of secondary syphilis – linear papules along the hairline JAAD 55:187–189, 2006 Tinea barbae – solitary papule or nodule Tinea faciei AD 114:250–252, 1978 Toxoplasmosis in AIDS AD 124:1446–1447, 1988 Trichodysplasia spinulosa – papovaviral infection of immunocompromised host; progressive alopecia of eyebrows initially, then scalp and body hair and red follicular papules of nose, ears, forehead; leonine facies JID Symposium Proceedings 4:268–271, 1999 Trichosporon asahi sepsis – personal observation Vegetating pyoderma Verruca vulgaris – single or multiple; flat warts Yaws – perioral and perinasal papules

454, 1987; AD 117:216–221, 1981; AD 116:565–567, 1980; AD 96:11–17, 1967; AD 88:586–596, 1963 Hashimoto-Pritzker disease (congenital self-healing reticulohistiocytosis) – red facial nodule JAAD 53:838–844, 2005 Hereditary progressive mucinous histiocytosis JAMADerm 152:1377–1378, 2016 Histiocytosis – non-Langerhans cell histiocytosis – generalized eruptive exanthem with recurrent crops of red-brown papules, including the face Acta DV 87:533–536, 2007; JAAD 50:116–120, 2004; Am J Dermatopathol 18:490–504, 1996; associated with acute myelogenous leukemia JAAD 50:116–120, 2004 Indeterminate cell histiocytosis – facial pink papules BJD 156:1357– 1361, 2007; Ped Derm 17:364–368, 2000 IgM storage papule – pink or skin colored BJD 106:217–222, 1982 Jessner's lymphocytic infiltrate BJD 161:583–590, 2009; AD 124:1091–1093, 1988 Juvenile xanthogranulomas – single or multiple Pediatr Rev 11(9):262–267, 1990; AD 125:1703–1708, 1989; AD 121:1531– 1541, 1985; generalized lichenoid juvenile xanthogranuloma – face, neck, scalp, upper trunk BJD 126:66–70, 1992; AD 112:43–44, 1976; eruptive JXGs Langerhans cell histiocytosis Jr Soc Med 75:279–81, 1982; urticating histiocytosis X JAAD 14:867, 873, 1986 Lichen myxedematosus (papular mucinosis) JAAD 33:37–43, 1995; discrete papular lichen myxedematosus Cutis 75:105–112, 2005; Acta DV 81:67–68, 2001; J Derm Surg Oncol 15:862–865, 1989 Mastocytoma – urticaria pigmentosa – single (mastocytoma) or multiple papules Pediatr Rev 11(9):262–267, 1990 Non-X histiocytosis JAAD 13:645–469, 1985

INFILTRATIVE DISEASES Amyloidosis – nodular amyloidosis AD 139:1157–1159, 2003 Angioplasmocellular hyperplasia – red nodule with red rim, ulcerated nodule, vascular nodule of face, scalp, neck, trunk, and leg JAAD 64:542–547, 2011 Benign cephalic histiocytosis – red-brown, pink-yellow papules of face or neck Ped Derm 36:411–413, 2019; Ped Derm 34:392–397, 2017; Ped Derm 31:547–550, 2014; cheeks, forehead, earlobes, neck JAAD 47:908–913, 2002; AD 135:1267–1272, 1999; Ped Derm 11:265–267, 1994; Ped Derm 11:164–167, 1994; Am J Dermatopathol 15:315–319, 1993; Ped Derm 6:198–201, 1989; AD 122:1038–43, 1986; JAAD 13:383–404, 1985; AD 120:650–655, 1984; Bull Soc Fr Dermatol Syphiligr 78:232–233, 1971 Colloid milium

Papular xanthoma Ped Derm 15:65–67, 1998; JAAD 22:1052–1056, 1990 Progressive mucinous histiocytosis AD 152:1377–1378, 2016; BJD 142:133–137, 2000 Progressive nodular histiocytosis JAAD 57:1031–1045, 2007; BJD 143:628–631, 2000 Self-healing (papular) juvenile cutaneous mucinosis – arthralgias Ped Derm 20:35–39, 2003; JAAD 44:273–281, 2001; Ped Derm 14:460–462, 1997; AD 131:459–461, 1995; JAAD 11:327–332, 1984; Ann DV 107:51–57, 1980; of adult JAAD 50:121–123, 2004; BJD 143:650–651, 2000; Dermatology 192:268–270, 1996 Xanthoma disseminatum – multiple papules Ped Derm 22:550–553, 2005; JAAD 23:341–346, 1990; multiple facial nodules flexural involvement JAAD 58:S47–49, 2008

Congenital self-healing histiocytosis Ped Derm 17:364–368, 2000 Eosinophilic granuloma – brown papule of pre-tragus Ped Derm 36:251–252, 2019 Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100; flat wart-like papules of face; bony lesions AD 143:952–953, 2007 Focal mucinosis – eyelid papule; chin papule J Craniofac Surg 21:1639–1641, 2010 Generalized eruptive histiocytomas – hundreds of skin-colored, brown, blue-red papules; resolve with macular pigmentation; face, trunk, proximal extremities Am J Dermatopathol March, 2015; An Bras Dermatol 88:105–108, 2013; JAAD 50:116–120, 395, 2004; BJD 150:171–173, 2004; Am J Dermatopathol 18:490–504, 1996; JAAD 31:322–326, 1994; JAAD 20:958–964, 1989; JAAD 17:499–

INFLAMMATORY DISEASES Eosinophilic pustular folliculitis -sterile papules, pustules, and plaques of face, trunk, arms, palms, soles JAAD 23:1012–1014, 1990; JAAD 14:469–474, 1986; eosinophilic folliculitis of AIDS J Dermatol 25:178–184, 1998; Ann DV 123:456–459, 1996; eosinophilic pustular folliculitis of infancy Ped Derm 21:615–616, 2004 Erythema multiforme Erythema nodosum Fatal bacterial granuloma after trauma – Chinese patients BJD 147:985–993, 2002 Idiopathic facial aseptic granuloma – facial papulonodule AD 137:1253–1255, 2001

Facial Papules Kikuchi’s disease (histiocytic necrotizing lymphadenitis) – red papules of face, back, arms; red plaques; erythema and acneform lesions of face; morbilliform, urticarial, and rubella-like exanthems; red or ulcerated pharynx; cervical adenopathy; associations with SLE, lymphoma, tuberculous adenitis, viral lymphadenitis, infectious mononucleosis, and drug eruptions Ped Derm 18:403– 405, 2001; JAAD 36:342–346, 1996; Am J Surg Pathol 14:872– 876, 1990 Lupus miliaris disseminata facei – affects central part of face, particularly the eyelid; it terminates spontaneously with scarring; histologically the papules show scattered epithelioid cell granulomas with caseation – mycobacteria are not recovered AD 130:369, 1994 Lymphadenoma – cutaneous lymphadenoma – red papules or nodules of face, head and neck JAAD 49:1115–1116, 2003; BJD 128:339–341, 1993 Lymphocytoma cutis – skin colored to plum-red dermal or subcutaneous nodules of cheek or nose; idiopathic or due to insect bites, Borrelia burgdorferi, trauma, vaccinations, injected drugs or antigens for hyposensitization, injection of arthropod venom, acupuncture, gold pierced earrings, tattoos, post-zoster scars JAAD 38:877–905, 1998; Cancer 69:717–724, 1992; Acta DV (Stockh)62:119–124, 1982; Cancer 24:487–502, 1969 Necrotizing folliculitis of AIDS Necrotizing infundibular crystalline folliculitis – follicular papules with waxy keratotic plugs; dome shaped waxy red papules of forehead, neck, and back; contain yeast and gram + bacteria JAMADerm 149:1233–1234, 2013; JAAD 66:823–826, 2012; BJD 145:165–168, 2001; BJD 143:310–314, 1999 Neutrophilic eccrine hidradenitis SKINMed 15:297–299, 2017 Nodular fasciitis – subcutaneous facial nodule AD 137:719–721, 2001; Ped Derm 17:487–489, 2000 Pseudofolliculitis barbae Pseudolymphomatous folliculitis – nodule AD 124:1271–1276, 1988 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – facial papules and nodules, purple plaques The Dermatologist, June 2018, pp47–50; Cutis 87: 296–299, 2011; JAAD 51:931–939, 2004; BJD 148:1060–1061, 2003; Semin Diagn Pathol 7:19–73, 1990; nasal red papule JAAD 71:412–414, 2014 Sarcoid – multiple facial papules AD 148:1097–1100, 2012; JAAD 66:699–716, 2012; AD 147:1332–1333, 2011; AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; Clinics in Chest Medicine 18:663–679, 1997 Subcutaneous fat necrosis of the newborn – facial nodule AD 134:425–426, 1998

METABOLIC

389

Kanzaki’s disease (alpha-N-acetylgalactosidase) – angiokeratoma corporis diffusum with lesions on face and extremities AD 129:460– 465, 1993; Ossifying fasciitis – red nodule of the nose JAAD 37:357–361, 1997 Osteoma cutis (miliary osteoma cutis) – most commonly in young women as a sequela of severe acne vulgaris; blue-brown discoloration has been described in patients treated with tetracycline or minocycline Cutis 86:100–102, 2010; Cutis 69:383–386, 2002; JAAD 44:96–99, 2001; AD 134:641–643, 1998; JAAD 38:906–910, 1998; AD 130:370, 373–374, 1994; JAAD 24:878–881, 1991 Oxalosis (primary oxalosis) – autosomal recessive; livedo reticularis, acrocyanosis, peripheral gangrene, ulcerations, sclerodermoid changes (woody induration of extremities), eschar of hand (calcium oxalate); acral and/or facial papules or nodules; end stage renal disease; primary hyperoxalosis – deficiency of alanine:glyoxylate aminotransferase; primary hyperoxalosis – deficiency of D-glycerate dehydrogenase/glyoxylate reductase AD 147:1277–1282, 2011; AD 131:821–3, 1995 Porphyria – variegate porphyria – central facial papules – lymphangiectasias JAAD 36:493–495, 1997 Xanthomas – Alagille syndrome Ped Derm 15:199–202, 1998; eruptive xanthomas xanthelasma of eyelids Zinc deficiency

NEOPLASTIC Acrochordon Actinic keratosis Adenoid cystic carcinoma – forehead papules JAAD 40:640–642, 1999 Adenoma sebaceum Angiofibromas – fibrous papule of nose JAAD 38:143–175, 1998; JAAD 10:670–671, 1984 Apocrine carcinoma Cancer 71:375–381, 1993 Apocrine hidrocystomas – blue cystic papule AD 134:1627–1632, 1998; AD 115:194–200, 1979; multiple papules AD 141:1365, 2005 Atypical fibroxanthoma Dermatol Ther 21:424–427, 2008; Cutis 51:47–48, 1993; Cancer 31:1541–1552, 1973; subcutaneous facial nodule AD 137:719–721, 2001 Basal cell carcinoma – single or multiple Acta Pathol Mibrobiol Scand 88A:5–9, 1980; multiple hereditary infundibulocystic basal cell carcinomas AD 135:1227–1235, 1999; intranasal basal cell carcinoma BJD 170:1369–1371, 2014 Basaloid follicular hamartoma (mimics trichoepithelioma) JAAD 27:237–240, 1992

Aspartylglucosaminuria – facial angiofibromas J Med Genet 36:398–404, 1999

Blue nevus

Calcinosis cutis – cutaneous calculus BJD 75:1–11, 1963; subepidermal calcified nodule – skin-colored Ped Derm 13:253–254, 1996; milia-like calcinosis cutis in Down’s syndrome Ped Derm 19:271– 273, 2002; subepidermal calcified nodule (Winer’s nodular calcinosis) Ped Derm 25:253–254, 2008

Cellular neurothekeoma Ped Derm 33:661–662, 2016

CD 34+ fibrous papule of the nose JAAD 35:342–345, 1996 Chondroid syringoma – solitary papule AD 125:1127–1132, 1989; of nose, cheek, forehead, chin Cutis 71:49–55, 2003 Chordoma, metastatic AD 141:1595–1600, 2005

Cystinosis – white facial papules; renal failure, ocular, pancreatic, hepatic, muscular, dental, gonadal, and neurologic involvement, hypothyroidism JAMADerm 152:108–109, 2016

Clear cell acanthoma – pink papule Ann Dermatol Syphilol 89:361–371, 1962

Fabry’s disease – red papules of face and lips BJD 166:712–720, 2012

Cylindroma – red nodule AD 129:495–500, 1993

Cutaneous horn

390 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Dermal dendrocytoma AD 126:689–690, 1990 Dermatofibroma – personal observation Dermatosis papulosa nigra Cutis 32:385–392, 1983; AD 89:655– 658, 1964 Dermoid cyst in adult – skin colored nodule of nose JAMA Derm 149:609–614, 2013

Cancer 5:539–550, 1952; one reported unilateral case AD 97:615–623, 1968 Kimura's disease – periauricular or submandibular subcutaneous nodule BJD 143:1338–1340, 2000; JAAD 38:143–175, 1998; JAAD 37:887–920, 1997 Leiomyomas JAAD 38:272–273, 1998

Desmoplastic trichilemmoma J Cutan Pathol 17:45–52, 1990

Leiomyosarcoma – cheek papule BJD 175:1104–1106, 2016

Desmoplastic trichoepithelioma – single papule JAAD 62:102–106, 2010; Clin Exp Dermatol 2:153–160, 1977; Cancer 40:2979–2986, 1977; AD 82:89–94, 1960; multiple familial JAAD 39:853–857, 1998

Leukemia cutis BJD 143:773–779, 2000; molluscum-like papules of HTLV-1 associated ATLL JAMA Derm 149:1101–1102, 2013; Indian J Dermtol 57:219–221, 2012; Acta DV 90:287–290, 2010; congenital acute lymphocytic leukemia; cutaneous sarcoid-like lesions of B-cell CLL JAAD 49:S180–181, 2003; chloroma – personal observation

Eccrine hidroadenoma – dermal nodule with or without ulceration; face, scalp, anterior trunk AD 97:651–661, 1968 Eccrine hidrocystomas JAAD 26:780–782, 1992; translucent papules of nose Ped Derm 28:53–54, 2011 Eccrine porocarcinoma JAAD 27:306–311, 1992; painful violaceous papule of temple Cutis 92:67–70, 2013 Eccrine poroma – solitary papule; nodule of nose JAAD 50:124– 126, 2004; skin colored papule of chin Ped Derm 22:279–280, 2005 Eccrine spiradenomas of forehead – Brooke-Spiegler syndrome (familial multiple eccrine spiradenomas with trichoepitheliomas) Cutis 46:46–50, 1990 Epidermal nevus Epidermoid cyst – single or multiple Epidermolytic acanthoma – keratotic papule AD 101:220–223, 1970 Epithelioid sarcoma – nose J Cutan Pathol 27:186–190, 2000 Fibrofolliculoma, solitary JAAD 76:S8–9, 2017; JAAD 11:361–363, 1984; JAAD 17:493–496, 1987 Folliculosebaceous cystic hamartoma – skin colored papule or nodule of central face or scalp; pedunculated or dome-shaped and umbilicated BJD 157:833–835, 2007; Clin Exp Dermatol 31:68–79, 2006; AD 139:803–808, 2003; JAAD 34:77–81, 1996; Am J Dermatopathol 13:213–220, 1991; J Cutan Pathol 7:394–403, 1980; nodule of nose AD 136:259–264, 2000 Folliculosebaceous smooth muscle hamartoma – pink-yellow domeshaped facial papule JAAD 56:1021–1025, 2007 Hair follicle nevus – skin-colored papules Ped Derm 25:60–62, 2008; Blaschko JAAD 46:S125–127, 2002; pedunculated papule Ped Derm 24:555–556, 2007; in distribution of first branchial arch Ped Derm 13:135–138, 1996 Hamartoma moniliformis – linear array of skin-colored papules of face and neck AD 101:191–205, 1970 Hidradenoma papilliferum JAAD 41:115–118, 1999 Hidrocystomas Hydroa vacciniforme-like Epstein-Barr virus-associated lymphoproliferative disease – crusted papules of face Ped Derm 96–100, 2012

Leukemid – granulomatous leukemid in myelodysplastic syndrome – personal observation Lichen planus-like keratosis Lipoma, facial Lymphadenoma, cutaneous (benign lymphoepithelial tumor of the skin) Ped Derm 25:413–414, 2008 Lymphoepithelioma-like carcinoma – subcutaneous skin colored nodule of face Cutis 101:170, 183–184, 2018 Lymphoma – B-cell lymphoma – nodule Ped Derm 21:525–533, 2004; JAAD 44:124–128, 2001; Am J Surg Pathol 10:454–463, 1986; primary cutaneous B-cell lymphoma BJD 153:167–173, 2005; cutaneous T-cell lymphoma – mimicking perioral dermatitis Clin Exp Dermatol 17:132–134, 1992; CD30+ lymphoma; anaplastic large cell T-cell lymphoma; HTLV-1 lymphoma, hydroa vacciniforme-like papulovesicular eruption of angiocentric lymphoma associated with Epstein-Barr virus AD 133:1081–1086, 1997; Hodgkin’s disease AD 127:405, 408, 1991; lymphomatoid granulomatosis AD 139:803– 808, 2003; hematodermic/plasmacytoid dendritic cell CD4+ CD56+ lymphoma – red nodules JAAD 58:480–484, 2008; Blood 99:1556– 1563, 2002; cutaneous anaplastic large cell lymphoma – facial ulcerated nodules AD 145:1399–1404, 2009; miliary and agminated primary follicle center lymphoma – multiple grouped papules of face, neck, trunk, and extremities JAAD 65:749–755, 2011; cutaneous T-cell lymphoma – skin colored facial nodule JAAD 67:736–744, 2012; cutaneous extranodal natural killer/T-cell lymphoma – black nasal papules; edematous cheek; red plaques of arms JAAD 70:716–723, 2014 Lymphomatoid papulosis – follicular lymphomatoid papulosis JAAD 68:809–816, 2013; facial and eyelid papules Ped Derm 31:103–104, 2014 Lymphotrophic adamantinoid trichoblastoma Ped Derm 24:157– 161, 2007 Malignant fibrous histiocytoma – facial pink papule JAAD 67:1335– 1341, 2012 Malignant histiocytosis – skin colored, red, violaceous papules or nodule (s) Hum Pathol 15:368–377, 1984

Inverted follicular keratosis J Clin Pathol 28:465–471, 1975

Melanocytic nevus

Kaposi’s sarcoma JAAD 41:860–862, 1999; JAAD 40:312–314, 1999

Melanoma – nodular melanoma; metastatic melanoma Semin Oncol 2:5–118, 1975; metastatic melanoma – 2 mm brown papules of face and neck Ped Derm 27:201–203, 2010; amelanotic melanoma – pink papule AD 139:1209–1214, 2003

JAAD 38:143–175, 1998; Dermatology 190:324–326, 1995 Keloid Keratoacanthoma – generalized eruptive keratoacanthoma of Grzybowski – facial and/or periorbital papules JAAD 37:478–480, 1997; JAAD 29:299, 1993; multiple self-healing keratoacanthomas of Ferguson-Smith – cluster around ears, nose, scalp JAAD 49:741–746, 2003; BJD 46:267–272, 1934; red nodule becomes ulcerated, resolve with crenellated scar; develop singly or in crops

Merkel cell carcinoma – pink to violaceous papule or nodule; red-pink vascular nodule of face JAAD 65:983–990, 2011; Sem Cut Med Surg 21:159–165, 2002; JAAD 43:755–767, 2000 Metastases, including testicular choriocarcinoma Cutis 67:117–120, 2001; sarcomatoid hepatocellular carcinoma BJD 148:1069–1071, 2003

Facial Papules

391

Microcystic adnexal carcinoma – skin-colored papule of the centro-facial region JAAD 45:283–285, 2001; Dermatol Surg 27:401–408, 2001; JAAD 41:225–231, 1999; JAAD 41:225–231, 1999

Porokeratosis – disseminated superficial porokeratosis – annular keratotic facial papules BJD 171:427–429, 2014

Milia, including multiple eruptive milia – face, earlobe JAAD 37:353–356, 1997; Cutis 60:183–184, 1997; Clin Exp Dermatol 21:58–60, 1996

Porokeratotic eccrine ostial and dermal duct nevus (linear eccrine nevus with comedones) – lesions of forehead AD 138:1309–1314, 2002

Mixed tumor of the face J Dermatol 23:369–371, 1996

Post-transplant lymphoproliferative disorder – violaceous macules and facial nodules Ped Derm 36:6810685, 2019

Moniliform hamartoma – papules of forehead and temples Mucinous eccrine carcinoma (mucinous carcinoma of skin) – gray nodule AD 136:1409–1414, 2000; Dermatol Surg 25:566–568, 1999; JAAD 36:323–326, 1997

Porokeratotic eccrine duct and hair follicle – filiform facial papules Ped Derm 27:514–517, 2010

Reed syndrome – leiomyomatosis; pink nodule JAMADerm 152:1041–1042, 2016

Multinucleate cell angiohistiocytoma BJD 133:308–310, 1995

Rhabdomyosarcoma Curr Prob Derm 14:41–70, 2002; JAAD 30:243–249, 1994

Multiple eruptive tumors of the follicular epithelium – hypopigmented facial papules AD 1356:463–468, 1999

Rhabdomyomatous mesenchymal hamartoma – pedunculated or sessile papule BJD 162:222–224, 2010

Multiple myeloma

Schwannomatosis AD 125:390–393, 1989

Myxoid fibroblastoma – nasal red papule JAAD 59:S61–64, 2008

Sebaceoma – multilobulated facial nodule AD 145:1325–1330, 2009

Nasal glioma

Sebaceous adenoma J Cutan Pathol 11:396–414, 1984

Neurilemmomas – linear array on forehead Clin Exp Dermatol 16:247–249, 1991

Sebaceous carcinoma Dermatol Ther 21:459–466, 2008; Br J Ophthalmol 82:1049–1055, 1998; Br J Plast Surg 48:93–96, 1995; JAAD 25:685–690, 1991; J Derm Surg Oncol 11:260–264, 1985; papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, pp. 40–41; morpheic plaque, blepharitis JAAD 14:668–673, 1986

Neurofibromas – single or multiple Neuromas, including palisaded encapsulated neuromas AD 140:1003–1008, 2004; AD 175:386–389, 1989; AD 106:865–870, 1972 Neurothekeoma – cellular neurothekeoma; pink papule of nose Ped Derm 29:658–659, 2012 Nevus sebaceus Osteosarcoma – primary cutaneous osteosarcoma JAAD 51:S94– 96, 2004 Osteoma cutis, post-acne – personal observation Palisaded encapsulated neuroma – skin colored papule of face Cutis 92:167, 177–178, 2013 Parotid tumor – subcutaneous facial nodule AD 137:719–721, 2001 Perifollicular fibroma AD 100:66–69, 1969 Pilar sheath acanthoma – umbilicated skin colored papule with central keratinous plug of moustache area AD 114:1495–1497, 1978 Pilar tumor of nose Cutis 36:251–252, 1985 Pilomatrixoma Curr Prob Derm 14:41–70, 2002; Pediatr Rev 11(9):262–267, 1990; Cancer 45:2368–2373, 1980; eruptive pilomatrixomas Ped Derm 30:756–758, 2013 Multiple pilomatrixomas seen in: Ped Derm 30:756–758, 2013   Familial Soto’s syndrome   Gardner’s syndrome   Gliomatosis cerebri   Myotonic dystrophy   Rubinstein-Taybi syndrome   Spina bifida   Trisomy 9   Turner’s syndrome   21-hydroxylase deficiency Plasmacytoid dendritic cell neoplasm – purple macules, violaceous papules, nodules, tumefactions; highly pigmented dark red, purpuric, necrotic lesions of face, neck JAAD 66:278–291, 2012 Plasmacytomas – red facial papules – primary cutaneous plasmacytomas J Dermatol 38:364–367, 2011; AD 145:299–302, 2009; Dermatology 189:251–255, 1994

Sebaceous hyperplasia JAAD 61:549–560, 2009; BJD 118:397– 402, 1988; Berlin:Verlag A Hirschfeld:1874; multiple facial sebaceous hyperplasias following Stevens-Johnson syndrome JAAD 65:446–448, 2011 Sebocystomatosis Int J Derm 35:734–735, 1996 Seborrheic keratosis Solitary fibrous tumor of the skin – facial nodule AD 142:921–926, 2006; JAAD 46:S37–40, 2002 Spitz nevus – single or multiple Pediatr Rev 11(9):262–267, 1990 Squamous cell carcinoma Striated muscle hamartoma AD 136:1263–1268, 2000; Ped Derm 16:65–67, 1999; Ped Derm 3:153–157, 1986 Syringocystadenoma papilliferum – solitary papule Syringomas – periorbital papules; forehead J Dermatol 23:61–63, 1996; milia-like syringomas Syringomatous carcinoma – skin colored facial nodule Cutis 77:19–24, 2006 Trichilemmal carcinoma JAAD 36:1021–1023, 1997 Trichilemmoma – single or multiple Trichoadenoma – solitary skin colored papule or nodule of face or buttock JAAD 62:277–283, 2010; Hautarzt 49:925–928, 1998; Arch Klin Exp Dermatol 207:34–45, 1958 Trichoblastic fibroma – solitary papule AD 131:198–201, 1995 Trichoblastoma – pink to skin colored papule Ped Derm 26:476– 477, 2009 Trichodiscoma – hypopigmented papules AD 126:1093, 1096, 1990; flat-topped papules of central face JAAD 15:603–607, 1986 Trichodysplasia of immunosuppression (trichodysplasia spinulosa, viral-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy); follicular crusted papules with keratotic spines; lesions of face, neck with eyebrow alopecia; trichodysplasia spinulosa-associated polyoma virus AD 147:1215– 1220, 2011; AD 142:1643–1648, 2006; JAAD 52:540–541, 2005

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Trichoepitheliomas (Brooke’s tumor) – single or multiple skin colored dome-shaped papules and nodules; multiple – cheeks, eyelids, nasolabial folds; upper trunk and arms; yellow to pink, bluish, telangiectasias on surface Ped Derm 23:399–401, 2006; Am J Dermatopathol 24:402–405, 2002; AD 126:953, 956, 1990; J Cutan Pathol 13:111–117, 1986; giant facial nodules BJD 149:674–675, 2003 Trichofolliculoma (on vermilion border) AD 86:619–625, 1962; tuft of hairs protruding centrally from dome-shaped papule AD 121:262–264, 1985; Tumor of follicular infundibulum – facial irregular nodules resemble basal cell carcinoma or keratosis JAAD 33:979–984, 1995

AD 143:841–844, 2007; JAAD 12:781–796, 1985; BJD 81:1–14, 1969 Chronic acquired dyskeratotic papulosis Cutis 69:469–471, 2002 Elastosis perforans serpiginosa AD 142:829–830, 2006 Facial Afro-Caribbean childhood eruption – resembles perioral dermatitis Clin Exp Dermatol 15:163–166, 1990; BJD 91:435–438, 1976 Fibroelastolytic papulosis of the neck – skin colored papules with cobblestoning of face and neck; possibly samd as white fibrous papulosis of neck or PXE-like papillary dermal elastolysis AD 148:849–854, 2012; BJD 173:461–466, 1997

Waldenstrom’s macroglobulinemia with lymphoplasmacytoid B cells – chest, earlobes, facial papules JAAD 45:S202–206, 2001

Frontal fibrosing alopecia – facial follicular papules BJD 169:217–218, 2013; AD 147:1424–1427, 2011; facial lesions – skin colored facial papules, follicular red dots, perifollicular and diffuse erythema with reticulated pattern, pigmented macules JAAD 73:987–990, 2015

PARANEOPLASTIC DISEASES

Granuloma annulare – forehead, scalp, and lower leg nodules in children JAAD 75:457–465, 2016; Pediatr Rev 11(9):262–267, 1990; photo-induced granuloma annulare of AIDS

Verrucous acanthoma – single or multiple

Eosinophilic dermatosis of myeloproliferative disease – face, scalp; scaly red nodules; trunk – red nodules; extremities – red nodules and hemorrhagic papules AD 137:1378–1380, 2001 Lymphoma – cutaneous granulomas associated with systemic lymphoma JAAD 51:600–605, 2004 Necrobiotic xanthogranuloma with paraproteinemia – multiple facial papules AD 145:279–284, 2009; facial nodule

Granuloma faciale JAAD 51:269–273, 2004 Granulomatous periorificial dermatitis – extrafacial and generalized periorificial dermatitis AD 138:1354–1358, 2002; facial granulomatous perioral dermatitis in children AD 125:369–373, 1989 Granulosis rubra nasi G Ital Dermatol Venereol 125:275–276, 1990 Infantile nodulocystic acne AD 123:432–433, 1987

JAAD 52:729–731, 2005

Keratosis lichenoides chronica Clin Exp Dermatol 27:283–285, 2002; BJD 144:422–424, 2001

Sterile suppurative folliculitis associated with acute myelogenous leukemia BJD 146:904–907, 2002

Keratosis pilaris, including scarring keratosis pilaris Lichen nitidus Ped Derm 26:109–111, 2009 Lichen striatus

PHOTOSENSITIVITY DISEASES Actinic superficial folliculitis BJD 139:359–360, 1998; BJD 138:1070–1074, 1998; Clin Exp Dermatol 14:69–71, 1989; BJD 113:630–631, 1985 Colloid milium AD 12:712, 715, 1986

Pityriasis lichenoides et varioliformis acuta – personal observation Pityriasis rosea Cutis 32:352–360, 1983 Pseudofolliculitis barbae Dermatol Clin 6:387–395, 1988 Reactive perforating collagenosis – familial RPC – umbilicated facial papules Ped Derm 30:762–764, 2013

Hydroa vacciniforme – red macules progress to tender papules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars JAAD 42:208–213, 2000; Dermatology 189:428–429, 1994; JAAD 25:892–895, 1991; JAAD 25:401–403, 1991; BJD 118:101– 108, 1988; BJD 118:101–108, 1988; AD 118:588–591, 1982; familial BJD 140:124–126, 1999; AD 114:1193–1196, 1978; AD 103:223–224, 1971; late onset BJD 144:874–877, 2001; hydroa vacciniforme (Epstein-Barr virus-related) – red macules progress to tender papules or vesiculopapules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of cheeks, eyelids, ears, and lips AD 142:587–595, 2006

Steatocystoma multiplex AD 122:205–207, 1986; Cutis 51:449–452, 1993; AD 129:35–37, 1993

Polymorphic light eruption – pinhead papular eruption of the face J Drugs in Dermatol 12:1285–1286, 2013

Atrichia with papular lesions – autosomal recessive; follicular cysts AD 139:1591–1596, 2003; JAAD 47:519–523, 2002; blue cystic papules of face, scalp, neck JID 118:887–890, 2002; JID 117:612– 617, 2001

PRIMARY CUTANEOUS DISEASES

Bannayan-Riley-Ruvalcaba syndrome (macrocephaly and subcutaneous hamartomas) (lipomas and hemangiomas) – autosomal dominant; multiple verrucous facial papules (trichilemmomas and warts) JAAD 68:189–209, 2013; JAAD 53:639–643, 2005; AD 132:1214–1218, 1996; AD 128:1378–1386, 1992; Eur J Ped 148:122–125, 1988; lipoangiomas (perigenital pigmented macules, macrocephaly) AD 128:1378–1386, 1992; lipomas in RuvalcabaMyhre-Smith syndrome Ped Derm 5:28–32, 1988

Acne rosacea (lupus miliaris disseminata faciei) AD 134:679–683, 1998; Clin Exp Dermatol 16:295–296, 1991; Int J Derm 23:542–544, 1984; acne agminata (granulomatous rosacea) – monomorphic brown papules of chin, cheeks, eyelids BJD 134:1098–1100, 1996 Acne vulgaris – inflammatory papules; multiple miliary osteoma cutis AD 110:113–114, 1974 Alopecia mucinosa – personal observation Angiolymphoid hyperplasia with eosinophilia – angiofibroma-like

Trichostasis spinulosa AD 133:1579, 1582, 1997

SYNDROMES Anhidrotic ectodermal dysplasia – carrier state for X-linked anhidrotic ectodermal dysplasia Atrichia with keratin cysts – face, neck, scalp; then trunk and extremities Ann DV 121:802–804, 1994

Basaloid follicular hamartoma syndrome – autosomal dominant; milia, comedone-like lesions, dermatosis papulosa nigra, skin

Facial Papules

393

tag-like lesions, hypotrichosis, multiple skin-colored, red, and hyperpigmented papules of the face in periorificial distribution, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes); hypohidrosis AD 144:933–938, 2008; Cutis 78:42–46, 2006; JAAD 49:698–705, 2003; BJD 146:1068–1070, 2002; JAAD 45:644–645, 2001; JAAD 43:189–206, 2000; JAAD 27:237–240, 1992; hypopigmented papules of face Ped Derm 16:281–284, 1999

14:41–70, 2002; Nat Genet 13:114–116, 1996; Dermatol Clin 13:27–31, 1995; AD 122:821, 824–825, 1986; Ann Intern Med 58:136–142, 1963; sclerotic fibromas; megalencephaly (macrocephaly), dysplastic gangliocytoma of the cerebellum (Lhermite-Duclos disease), hamartomatous intestinal polyposis AD 142:625–632, 2006; J Cut Pathol 19:346–351, 1992

Bazex-Dupre-Christol syndrome – X-linked dominant; facial trichoepitheliomas JAAD 74:437–451, 2016

Cutaneous segmental heterotopic meningeal tissue with multifocal neural and mesenchymal hamartomas – skin colored pedunculated papules of forehead, eyelids, scalp, ala nasi; hypertrichotic heterotopic meningeal nodule BJD 156:1047–1050, 2007

Behcet’s syndrome – erythema nodosum; nodule AD 138:467–471, 2002 Birt-Hogg-Dube syndrome – fibrofolliculomas – autosomal dominant; white or yellow facial and nose papules; comedo-like white papules, pedunculated lip papules of mucosal surface, thyroid nodules or cysts; mutation in FLCN (folliculin) gene AD 147:499– 504, 2011; AD 146:1316–1318, 2010; BJD 162:527–537, 2010; Am J Resp Crit Care Med 175:1044-­1-­53, 2007; JAAD 50:810–812, 2004; JAAD 49:698–705, 2003; Australas J Dermatol 44:52–56, 2003; JAAD 48:111–114, 2003; AD 135:1195–1202, 1999; JAAD 16:452–457, 1987; AD 133:1161–1166, 1997; AD 113:1674–1677, 1977; renal and colonic neoplasms Cancer Epidemiol Biomarkers Prev 11:393–400, 2002; AD 135:1195–1202, 1999; facial angiofibromas JAAD 53:S108–111, 2005 Blue rubber bleb nevus syndrome Brooke-Spiegler syndrome – trichoepitheliomas, spiradenomas, and cylindromas SKINmed 13:325–328, 2015; JAAD 49:698–705, 2003; Dermatol Surg 26:877–882, 2000; also eccrine spiradenomas of forehead Am J Dermatopathol 20:56–60, 1998; Cutis 46:46–50, 1990 Carney complex (NAME/LAMB syndrome) – autosomal dominant; pink papules of face (myxomas); multiple lentigines of upper lips, genitalia, conjunctivae, inner and outer canthi, palms, vulva, penis, melanocytic nevi, small blue nevi, cutaneous myxomas (red papules or pedunculated papules), psammomatous schwannoma, cardiac myxomas, testicular Sertoli cell tumors, gynecomastia, myxoid breast fibroadenomas, pituitary adenomas, acromegaly, testicular calcification, thyroid carcinoma, breast ductal carcinoma, osteochondromyxoma, thyroid disease, Cushing’s syndrome due to primary pigmented nodular adreno-cortical disease; growth hormone-producing pituitary adenomas; large-cell calcifying Sertoli cell tumor of the testis; PRKAR1A (protein kinase A type-1 regulatory subunit of cAMP dependent protein kinase A); lentigines fade with time JAAD 61:80–87, 2009; JAAD 59:801–810, 2008; JAAD 46:161–183, 2002; Molec Genet Metab 78:83, 2003; J Clin Endocrinol 86:4041, 2001; Curr Prob in Derm VII:143–198, 1995; Medicine (Baltimore) 64:270–283, 1985; Br Heart J 35:874–876, 1973; conjunctival lentigines JAAD 42:145, 2000; epithelioid blue nevus and psammomatous melanotic schwannoma Semin Diagn Pathol 15:216–224, 1998; J Clin Invest 97:699–705, 1996; Dermatol Clin 13:19–25, 1995; JAAD 10:72–82, 1984 Costello syndrome - warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977 Cowden’s syndrome (PTEN hamartoma-tumor syndrome) – trichilemmomas (wart-like papules), especially periorificial facial papules AD 146:337–342, 2010; JAAD 49:698–705, 2003; Curr Prob Derm

Cri du chat syndrome (chromosome 5, short arm deletion syndrome) – premature greying of the hair, pre-auricular skin tag with low-set malformed ears J Pediatr 102:528–533, 1983

Deletion of short arm of chromosome 4 (4p- syndrome) – ACC of scalp with hypertelorism, beaked or broad nose, microcephaly, low set ears, pre-auricular tags or pits, mental retardation Am J Dis Child 122:421–425, 1971 Delleman-Oorthuys syndrome – oculocerebrocutaneous syndrome – eyelid tag, periorbital tags, pre-auricular, post-auricular skin tags; facial tags, orbital cysts, focal punched-out skin defects of the ala nasi, microphthalmia, eyelid coloboma, cerebral abnormalities, seizures, developmental delay Ped Derm 24:657–658, 2007; Clin Dysmorphol 7:279–283, 1998; Am J Ophthalmol 99:142–148, 1985; pedunculated facial papules and atrophic patches of neck; accessory tragi and aplasia cutis congenita AD 147:345–350, 2011; J Med Genet 25:773–778, 1988 Dermochondrocorneal dystrophy AD 124:424–428, 1988 Down’s syndrome – milia-like idiopathic calcinosis cutis BJD 134:143–146, 1996 EEC syndrome – perioral papillomatosis Ped Derm 19:330–332, 2002 Encephalocranial lipomatosis – lipomatous hamartomas of scalp and eyelids; lipomas, lipofibromas, connective tissue nevi – facial papules and/or nodules; linear yellow papules of forehead extending to eyelids; ophthalmologic manifestations; seizures, mental retardation; mandibular or maxillary ossifying fibromas and odontomas; cranial asymmetry; developmental delay, mental retardation, seizures, spasms of contralateral limbs; unilateral porocephalic cysts with cortical atrophy AD 144:266–268, 2008; Ped Derm 23:27–30, 2006; Ped Derm 22:206–209, 2005; JAAD 47:S196–200, 2002; Am J Med Genet 191:261–266, 2000; JAAD 37:102–104, 1998; Ped Derm 10:164–168, 1993; BJD 104:89–96, 1981; Arch Neurol 22:144–155, 1970 Epidermodysplasia verruciformis – flat-topped red papules of face BJD 175:803–806, 2016; J Drugs Dermatol 15:350–352, 2016; J Cut Med Surg 8:357–360, 2004; J Eur Acad Derm Venereol 17:382–386, 2003; Curr Top Microbiol Immunol 186:157–175, 1994; hyperpigmented papules of face – atypical EDV with LCK mutation BJD 175:1204–1209, 2017 Facial and neck papillomas, acanthosis nigricans, macrocephaly, mental retardation, cerebral angiomatosis AD 128:1378–1386, 1992 Familial multiple discoid fibromas (Birt-Hogg-Dube look-alike) – red papules of cheeks, around nose, helices and posterior ears, skin colored papules with overlying telangiectasias; white papules of face and ears BJD 169:177–180, 2013; JAAD 66:259–263, 2012 Familial sea-blue histiocytosis – autosomal recessive; patchy gray pigmentation of face, upper chest, shoulders; eyelid edema, facial nodules Dermatologica 174:39–44, 1987 Farber's disease (lipogranulomatosis) Pediatr Rev 11(9):262–267, 1990 Fibrodysplasia ossificans progressive

394 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Francois syndrome (dermochondrocorneal dystrophy) – knuckle pads; nodules on hands, nose, and ears AD 124:424–428, 1988; Ann DV 104:475–478, 1977 Goldenhaar's syndrome - oculoauriculovertebral syndrome – accessory tragi (preauricular tags); ocular lipodermoids, epibulbar dermoids; multiple vertebral anomalies, gastrointestinal anomalies, microphthalmia, anophthalmia, colobomata, genital anomalies, micrognathia, microtia, cleft lip/palate, hemifacial microsomia, urologic anomalies, cardiac anomalies, pulmonary anomalies Ped Derm 24:657–658, 2007; JAAD 50:S11–13, 2004 Goltz's syndrome – wart-like lesions on face and groin Haber's syndrome – rosacea-like acneform eruption with erythema, telangiectasia, prominent follicles, comedones, small papules, atrophic pitted scars; with keratotic plaques of the trunk and extremities AD 103:452–455, 1971; BJD 77:1–8, 1965 Hemifacial microsomia syndrome – preauricular tags Hereditary progressive mucinous histiocytosis – yellow domeshaped papules of face, gingiva, hard palate BJD 141:1101–1105, 1999 IgG4 disease – red facial papules; fibrous mass formations, lymphadenopathy JAMADerm 152:569–570, 2016 Infantile systemic hyalinosis – autosomal recessive; red pearly facial papules, synophrys, thickened skin, perianal nodules, dusky red plaques of buttocks, gingival hypertrophy, joint contractures, juxta-articular nodules (knuckle pads), osteopenia, growth failure, diarrhea, frequent infections; mutation in CMG 2 (capillary morphogenesis protein 2) JAAD 58:303–307, 2008; JAAD 50:S61–64, 2004; Pediatr Pathol 6:55–79, 1986 Juvenile hyaline fibromatosis (Murray-Puretic syndrome) – autosomal recessive; translucent pearly white papules or nodules of scalp, face (chin, nasolabial folds, forehead, ears, back of, neck, perianal nodules), trunk, gingival hypertrophy, larger papules and nodules around nose, behind ears, on fingertips, multiple subcutaneous nodules of scalp, trunk, and extremities, flexion contractures of large and small joints papillomatous perianal papules; joint contractures, skeletal lesions, gingival hyperplasia, stunted growth, sclerodermiform atrophy; infiltration of small and large intestine; CMG2 (capillary morphogenesis gene 2) gene JAAD 61:695–700, 2009; JAAD 58:303–307, 2008; Eur J Pediatr 168:363–365, 2008; Ped Derm 21:154–159, 2004; Arch Ped 4:1200–1204, 1997; JAAD 16:881–883, 1987; perinasal and fold of chin Ped Derm 6:68–75, 1989 Lipoid proteinosis – yellow-brown nodules of face Int J Derm 39:203–204, 2000; Acta Paediatr 85:1003–1005, 1996; JAAD 27:293–297, 1992; crusted red papules of face heal with scarring Ped Derm 22:266–267, 2005; Arch Pathol Anat 273:286–319, 1929 Muir-Torre syndrome – autosomal dominant; sebaceous adenomas, sebaceous carcinomas, keratoacanthomas Cutis 87:125–128, 2011; AD 142:1039–1042, 2006; Cutis 75:149–155, 2005; Curr Prob Derm 14:41–70, 2002; BJD 136:913–917, 1997; JAAD 33:90–104, 1995; JAAD 10:803–817, 1984; AD 98:549–551, 1968; Br J Surg 54:191–195, 1967 Multicentric reticulohistiocytosis – perioral 1 mm dome shaped papules AD 148:228–232, 2012; Clin Exp Rheumatol 23:97–99, 2005; AD 126:251–252, 1990 Multiple endocrine neoplasia syndrome (MEN I) (Wermer's syndrome) – angiofibromas of face and nose J Clin Endocrinol Metab 89:5328–5336, 2004; Endocr J 47:569–573, 2000; JAAD 42:939–969, 2000; JAAD 41:890–892, 1999; AD 133:853–857, 1997; angiofibromas of vermilion border; facial angiofibromas,

lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia; mutation in menin, a nuclear protein involved in cell cycle regulation and proliferation JAAD 61:319–324, 2009; AD 133:853–857, 1997 Multiple eccrine-pilar hamartomas with basal cell carcinomas – multiple follicular hamartomas, vermiculate atrophoderma, milia, hypotrichosis, and basal cell carcinomas JAAD 39:853–857, 1998 Multiple hereditary infundibulocystic basal cell carcinoma syndrome – germline SUFU mutation JAMADerm152:323–327, 2016; JAAD 51:989–995, 2004; AD 135:1227–1235, 1999 Neurofibromatosis type 1 – personal observation Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – autosomal dominant; papules of the face, neck, and trunk, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, basal cell carcinomas; also medulloblastomas, ovarian tumors, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas BJD 174:68–76, 2016; Int J Oral Maxillofac Surg 33:117–124, 2004; Am J Med Genet 69:299–308, 1997; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; AD 114:95–97, 1978; Birth Defects 8:140–148, 1971 Pachyonychia congenita – steatocystomas Ped Derm 30:387–388, 2013 Pfeiffer syndrome – pre-auricular tag, syndactyly, craniosynostosis, broad great toes, gingival hypertrophy Z Kinderheilkd 90:301–320, 1964 Proteus syndrome – facial nodule Reticular erythematous mucinosis (REM) syndrome Rombo syndrome – papules and cysts of the face and trunk, basal cell carcinomas, vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, peripheral vasodilatation with cyanosis JAAD 39:853–857, 1998 Sakati syndrome – patchy alopecia with atrophic skin above ears, submental linear scars, acrocephalopolysyndactyly, short limbs, congenital heart disease, abnormally shaped low-set ears, ear tag, short neck with low hairline J Pediatr 79:104–109, 1971 Schnitzler’s syndrome – urticaria and IgM monoclonal paraprotein Steatocystoma multiplex – facial papular variant AD 131:835, 838, 1995 Townes-Brocks syndrome – lop ears, preauricular tags Ped Derm 24:657–658, 2007; Dysmorphol Clin Genet 2:104–108, 1988 Treacher Collins syndrome – multiple accessory tragic (facial skin tags) Ped Derm 24:657–658, 2007 Tuberous sclerosis – adenoma sebaceum (angiofibromas); mutations or TSC1 and TSC2 Ped Derm 32:563–570, 2015; JAAD 73:802–808, 2015; JAMADerm 150:1095–1101, 2014; Ped Neurol 49:243–254, 2013; BJD 165:912–916, 2011; AD 146:715–718, 2010; JAAD 57:189–202, 2007; JAAD 49:698–705, 2003; BJD 147:337–342, 2002; JAAD 45:731–735, 2001; Derm Surg 27:486– 488, 2001; J Child Neurol 13:624–628, 1998; BJD 135:1–5, 1996; JAAD 32:915–935, 1995; J Clin Neurol 7:221–224, 1992; Ped Clin North Amer 38:991–1017, 1991; S Med J 75:227–228, 1982; fibrous cephalic plaques JAAD 78:717–724, 2018 Turner’s syndrome – multiple pilomatrixomas; facial papules; may be multilobulated JAMA Derm 149:559–564, 2013 VACTERL syndrome Ped Derm 24:657–658, 2007

Facial Plaques, Scarring and Non-scarring Winchester syndrome – hyalinosis, joint contractures, hirsutism, corneal opacity Wells' syndrome – facial nodules AD 142:1157–1161, 2006; Ped Derm 14:312–315, 1997; AD 125:1625–1626, 1989 Wolf-Hirschhorn syndrome – del (4p) syndrome – preauricular tag or dimple, craniofacial asymmetry, mental and growth retardation, eye lesions, cleft lip and palate, cardiac defects Ped Derm 24:657– 658, 2007; Eur J Hum Genet 8:519–526, 2000

395

 ACIAL PLAQUES, SCARRING F AND NON-SCARRING  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – to injected bovine collagen

Xeroderma pigmentosum

Brunsting-Perry pemphigoid simulating basal cell carcinoma JAAD 21:331–334, 1989

TOXINS

Chronic granulomatous disease – DLE-like plaque AD 126:1656– 1658, 1990; X-linked chronic granulomatous disease – discoid lupus-like lesions of face and hands in female carriers of X-linked chronic granulomatous disease BJD 104:495–505, 1981

Thallium poisoning – generalized hyperpigmentation; anagen effluvium, gastrointestinal upset, visual impairment, Mees’ lines, perioral dermatitis, scaling of palms and soles, acneiform eruptions; treat with Prussian blue JAMADerm 152:724–726, 2016

TRAUMA

Combined immunodeficiency – cutaneous granuloma JAAD 25:761–766, 1991 Common variable immunodeficiency – red plaque with scale and atrophy Ped Derm 12:170–173, 1995; granulomatous dermatitis AD 142:783–784, 2006

Aneurysm of superficial temporal artery

Lupus erythematosus – discoid lupus erythematosus NEJM 269:1155–1161, 1963; lupus panniculitis Ped Derm 29:169–176, 2012; lupus panniculitis including patients with partial C2 or C4 deficiencies AD 122:576–582, 1986; tumid LE AD 136:1033–1041, 2000; periorbital red plaque BJD 157:1081–083, 2007; discoid lupus with annular atrophic plaques of face, neck, behind ears AD 112:1143–1145, 1976; systemic, subacute cutaneous; lupus profundus; tumid lupus – annular plaque without scale BJD 162:64–73, 2010; AD 145:244–248, 2009

Angioleiomyoma JAAD 38:143–175, 1998

Morphea, linear (en coup de sabre) – generalized morphea

Angiolymphoid hyperplasia with eosinophilia – disseminated papules over entire face Cutis 72:323–326, 2003; papules and/or nodules along hairline AD 136:837–839, 2000; angiofibroma-like JAAD 12:781–796, 1985

Pemphigus erythematosus – red plaques of cheeks JAMADerm 151:1123–1124, 2015

Acanthoma (granuloma) fissuratum

VASCULAR Acral arteriovenous hemangioma Dermatologica 113:129–141, 1956

Eosinophilic granulomatosis with polyangiitis – necrotic eschar within red plaque; red papules of forehead and scalp JAAD 65:244–246, 2011 Eosinophilic vasculitis syndrome Sem Derm 14:106–110, 1995 Eruptive pseudoangiomatosis – red papules Ped Derm 19:243–245, 2002; BJD 143:435–438, 2000 Hemangioma – focal hemangioma AD 139:869–875, 2003 Hemangiopericytoma Hobnail hemangioma – vascular papules of the nose BJD 146:162– 164, 2002 Microscopic polyangiitis AD 133:474–477, 1997 Multiple progressive angioma – blue compressible nodules on face of children or teenagers; may be distributed along vein Acta DV (Stockh) 31:304–307, 1951 Neonatal hemangiomatosis Polyarteritis nodosa, systemic; cutaneous (livedo with nodules) – painful or asymptomatic red or skin colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk Ped Derm 15:103–107, 1998; AD 130:884–889, 1994; JAAD 31:561–566, 1994; JAAD 31:493–495, 1994 Pyogenic granuloma Pediatr Rev 11(9):262–267, 1990 Spindle cell hemangioendothelioma – pink papule of nose AD 138:259–264, 2002 Temporal arteritis – nodules over temporal or facial arteries BJD 76:299–308, 1964

Pemphigus foliaceus Pemphigus vulgaris PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAMADerm 151:627–634, 2015 Scleroderma Sjogren's syndrome – annular erythema JAAD 20:596–601, 1989 Still’s disease Urticaria

DRUG Bromoderma Chlorambucil – butterfly cellulitis-like plaque AD 122:1358–1360, 1986 Chlorpromazine-induced lupus-like disease JAAD 13:109–115, 1985 Cyclosporine – plaques JAAD 23:1137–1141, 1990 Cytarabine – neutrophilic eccrine hidradenitis J Drugs Dermatol 12:231–232, 2013 Fixed drug eruption – personal observation

396

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Granulocyte colony stimulating factor – exudative and erosive facial plaques; neutrophilic dermatosis associated with myelodysplastic syndrome AD 144:643–648, 2008

Cryptococcosis – verrucous plaques of face in HIV disease with IRIS Clin Inf Dis 56:117, 159–160, 2013

Infliximab – tumid lupus AD 142:115–116, 2006

Dermatophytosis with immunosuppression – personal observation

Iododerma

Emmonsia pasteuriana – dimorphic fungus; disseminated infection in South Africa; lichenoid diffuse papulosquamous eruption; crusted verrucous facial nodules and plaques NEJM 369:1416–1424, 2013

MESNA drug reaction mimicking worsening of SLE AD 128:80–82, 1992 Methotrexate-associated lymphoproliferative disorder – red papules and plaques of nose, cheeks, eyelids JAAD 56:686–690, 2007 Piroxicam photodermatitis Post-steroid panniculitis Ped Derm 5:92–93, 1988 Pseudolymphoma, drug induced – anticonvulsants Rook, pp. 2401– 2402, 1998, Sixth Edition; captopril, enalapril J Clin Pathol 39:902–907, 1986; atenolol Clin Exp Dermatol 115:119–120, 1990; ACE-inhibitors, amitryptiline Curr Probl Dermatol 19:176–182, 1990 Voriconazole – voriconazole photosensitivity with red plaques on cheeks in patient with chronic granulomatous disease JAAD 70:576–580, 2014

EXOGENOUS AGENTS Bovine collagen – granulomatous reaction; linear red plaques of nasolabial folds JAAD 64:1–34, 2011 Calcinosis cutis due to EEG paste – annular forehead plaque AD 138:405–410, 2002 Polymethylmethacrylate filler – treatment with interferon-alpha and ribavirin AD 143:507–510, 2007 Polymethylmethacrylate microsphere and bovine collagen (Artecoll) – granulomatous reaction; red plaques of cheeks JAAD 64:1–34, 2011 Silica granuloma – red plaques JAAD 52:S53–56, 2005; Ped Derm 20:40–43, 2003

INFECTIONS OR INFESTATIONS Alternariosis, dermal AD 124:1822–1825, 1988 Amebiasis – Balamuthia mandrillaris; granulomatous facial plaque JAAD 60:897–925, 2009 Balamuthia mandrillaris – violaceous plaques of face; encephalitis JAAD 75:19–30, 2016 Candida Cellulitis/erysipelas – streptococcal; Groups A, B (infants under 3 months Am J Dis Child 136:631–633, 1982; C, and G AD 130:1150–1158, 1994; Hemophilus influenzae – facial cellulitis in children; Streptococcus pneumoniae Clin Inf Dis 14:247–250, 1992; Pseudomonas aeruginosa JAMA 248:2156–2157, 1982; Campylobacter jejuni Eur J Clin Microbiol Infect Dis 11:842–847, 1988; congenital neutropenia Blood Rev 2:178–185, 1988; Am J Med 61:849–861, 1976; in leukocyte adhesion deficiency (beta 2 integrin deficiency) – abscesses, cellulitis, skin ulcerations, ulcerative stomatitis BJD 139:1064–1067, 1998; J Pediatr 119:343– 354, 1991; Ann Rev Med 38: 175–194, 1987; J Infect Dis 152:668– 689, 1985 Chromomycosis BJD 146:704, 2002; AD 133:1027–1032, 1997 Coccidioidomycosis Cutis 85:25–27, 2010; AD 123:937–942, 1987; red plaque, verrucous facial plaques JAAD 55:929–942, 2006; Philadelphia Med J5:1471–1472, 1900; An Circ Med Argent 15:585–597, 1892 Coelenterates – delayed reaction JAAD 10:462–466, 1984

Demodicidosis JAAD 52:S59–61, 2005

Erysipelas Fusarium solani – hyperkeratotic facial plaque Ped Derm 9:62–65, 1992; AD 101:598–600, 1970; Fusarium solani – target-like lesions with central necrosis Eur J Clin Microbiol Infect Dis 13:152–161, 1994 Gianotti-Crosti syndrome Herpes zoster – red plaque with necrosis Cutis 96:364–390, 2015 Histoplasmosis Insect bite Leishmaniasis – erysipeloid leishmaniasis Clin Dermatol 38:140– 151, 2020; chronic cutaneous tumid leishmaniasis infiltrated nasal plaque – mucocutaneous leishmaniasis JAMA 312:1250–1251, 2014; red plaque JAAD 50:812–813, 2004; crusted red plaques JAAD 59:540–542, 2008; red plaque of cheek in AIDS BJD 160:311–318, 2009; annular plaque of recurrent leishmaniasis (lupoid leishmaniasis) Conn Med 65:333–337, 2001; Cutis 37:177–179, 1986; leishmania recidivans – central atrophy with verrucous border Clin Dermatol 38:140–151, 2020 Leprosy – tuberculoid – well-defined edge, red, copper or purple colored plaque with hypopigmented center; annular pink plaque of temple JAAD 60:1018–1021, 2009; hairless; Lucio's phenomenon – firm subcutaneous plaque AD 114:1023–1028, 1978; borderline tuberculoid leprosy – red plaque of face JAAD 55:714–716, 2006; borderline lepromatous leprosy Clin Inf Dis 50:1015–1016, 1068–1069, 2010; type 1 reaction in borderline type 1 leprosy reaction – papules and plaques on tragus; plaque of face JAMA Derm 149:74–78, 2013; lepromatous leprosy – skin colored plaques Lyme disease – acute or recurrent, including acrodermatitis chronica atrophicans Dermatology 189:430–431, 1994 Malassezia pachydermatis – verrucous plaque of the face AD 142:1181–1184, 2006 Mycobacterium avium complex – plaque of earlobe, ear, and cheek Lancet Infect Dis 9:136, 2009 Mycobacterium avium intracellulare complex – resembling lupus vulgaris BJD 136:264–266, 1997 Mycobacterium bovis – lupus vulgaris BJD 153:220–222, 2005 Mycobacterium tuberculosis – lupus vulgaris – “turkey ear” BJD 157:816–818, 2007; – ulcerated plaque of buttocks BJD 146:525– 527, 2002; JAAD 26:404–407, 1992; Medicine 60:95–109, 1980; starts as red-brown plaque, enlarges with serpiginous margin or as discoid plaques; apple-jelly nodules; plaque form – psoriasiform, irregular scarring, serpiginous margins; ulcerative and mutilating forms, vegetating forms – ulcerate, areas of necrosis, invasion of mucous membranes with destruction of cartilage (lupus vorax); tumor-like forms – deeply infiltrative; soft smooth nodules or red-yellow hypertrophic plaque; myxomatous form with large tumors of the earlobes; lymphedema prominent; papular and nodular forms; nasal, buccal, and conjunctival involvement with friable nodules which ulcerate; vegetative and ulcerative lesions of buccal mucosa, palate, gingiva, oropharynx; head, neck, around nose, extremities, trunk Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39 (Suppl 49):1–137, 1960; M. africanum (M. tuberculosis complex) – circinate and annular facial plaques, around nose J Clin Inf Dis

Facial Plaques, Scarring and Non-scarring 21:653–655, 1995; tuberculous gumma (metastatic abscess) Dermatol Clin 26:285–294, 2008 Necrotizing fasciitis North American blastomycosis – red plaque with pustules JAAD 53:740–741, 2005; disseminated NAB – giant plaques Clin Inf Dis 55:1390–1391, 1426–1428, 2012 Paecilomyces lilacinus – red scaly plaques of the face JAAD 39:401–409, 1998; JAAD 35:779–781, 1996

397

Reticulohistiocytosis – diffuse cutaneous reticulohistiocytosis Rosai-Dorfman disease (sinus histiocytosis) Acta DV 79:363–365, 1999 Scleromyxedema – red plaque of moustache area Cutis 85:137– 140, 2010 Self-healing juvenile cutaneous mucinosis JAAD 11:327–332, 1984 Xanthoma disseminatum JAAD 23:341–346, 1990

Paracoccidioidomycosis – verrucous multinodular plaque Clin Dermatol 38:152–159, 2020; JAAD 53:931–951, 2005; Cutis 40:214–216, 1987

INFLAMMATORY DISEASE

Pott's puffy tumor – nontender bogginess of forehead – underlying osteomyelitis

Acquired lacrimal sac fistula due to dacryocysitis – ulcers around medial canthus BJD 168:1348–1350, 2013

Protothecosis BJD 146:688–693, 2002

Crohn’s disease – metastatic Crohn's disease AD 129:1348–1351, 1993; JAAD 36:986–988, 1996

Pseudomonas sepsis Rhinoscleroma Schistosomiasis Derm Clinics 17:151–185, 1999; S. mansoni BJD 103:205–208, 1980 Scopulariopsis brevicaulis JAAD 39:365–367, 1998 Spider bite Sporotrichosis – fixed cutaneous sporotrichosis – mountain range red plaque of face Cutis 96:218, 227–228, 2015 Sycosis barbae – deep staphylococcal folliculitis; red plaque studded with pustules Dermatol Wochenschr 152:153–167, 1966 Syphilis, tertiary (nodular, tubercular) – annular, circinate nodules and plaques of face Rook, p. 1250, 1998, Sixth Edition

Kikuchi’s disease (histiocytic necrotizing lymphadenitis) – red papules of face, back, arms; red plaques; erythema and acneform lesions of face; morbilliform, urticarial, and rubella-like exanthems; red or ulcerated pharynx; cervical adenopathy; associations with SLE, lymphoma, tuberculous adenitis, viral lymphadenitis, infectious mononucleosis, and drug eruptions BJD 144:885–889, 2001; Am J Surg Pathol 14:872–876, 1990 Lymphocytoma cutis Cancer 69:717–724, 1992; Acta DV (Stockh)62:119–124, 1982; Cancer 24:487–502, 1969; lymphocytoma cutis due to Borrelia infection – red plaques of eyebrows AD 144:673–678, 2008 Malakoplakia Dermatology 194:358–360, 1997

Tinea barbae – Trichophyton verrucosum Clin Infect Dis 23:1308– 1310, 1996; Trichophyton rubrum JAAD 18:403–406, 1988

Neutrophilic eccrine hidradenitis – red plaques of face JAAD 56:693–696, 2007; AD 139:531–536, 2003

Tinea faciei Ped Derm 29:249–253, 2012; Microsporum canis – annular scaly plaques of face Ped Derm 29:409–413, 2012; AD 114:250–252, 1978; JAMA 215:2091–2094, 1971; invasive dermatophytosis; tinea incognito

Neutrophilic sebaceous adenitis – red/purple plaques AD 129:910– 911, 1993; annular erythematous indurated plaques of face and chest in photodistribution JAAD 60:887–888, 2009; annular expanding red plaques of face and back with fever, lymphadenopathy JAMADerm 150:1225–1226, AD 129:910–911, 1993

Yaws, early

Pyoderma gangrenosum

INFILTRATIVE DISEASES Alopecia mucinosa (follicular mucinosis) BJD 163:420–423, 2010; AD 141:897–902, 2005; Ped Derm 16:326–328, 1999

Sarcoid yellow-red plaque of face and scalp BJD 175:1111–1112, 2016; AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; Clinics in Chest Medicine 18:663–679, 1997

Amyloidosis – nose plaque; nodular localized primary cutaneous amyloidosis BJD 145:105–109, 2001; brown facial plaque BJD 158:860–862, 2008

METABOLIC

Colloid milium South Med J 89:1004–1007, 1996; juvenile colloid milium – yellow facial plaques JAAD 49:1185–1188, 2003

Cryoglobulinemia – monoclonal cryoglobulins

Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100; xanthelasma-like lesions; flat wart-like papules of face; bony lesions AD 143:952–953, 2007; Hautarzt 52:510–517, 2001; Medicine (Baltimore) 75:157–169, 1996 Follicular mucinosis of childhood – red facial plaques, hypopigmented facial plaques, follicular papules; alopecic scaly plaque of face (follicular mucinosis in childhood) Ped Derm 30:192–198, 2013 Jessner's lymphocytic infiltrate JAAD 23:63–67, 1990; AD 124:1091–1093, 1988; Arch Dermatol Syphil 68:447–449, 1953 Juvenile xanthogranuloma, plaque-type – red plaques of face JAAD 59:S56–57, 2008 Langerhans cell histiocytosis Lymphocytoma cutis – personal observation

Calcinosis cutis Hepatoerythropoietic porphyria – annular plaques of nose and face BJD 151:920–923, 2004 IgM storage papule BJD 106:217–222, 1982 Necrobiosis lipoidica diabeticorum AD 130:1433, 1436, 1994; Acta DV 58:276–277, 1978; BJD 89 (Suppl 9):100–101, 1973 Platelike osteoma cutis AD 143:109–114, 2007

NEOPLASTIC Angiosarcoma of face and scalp (Wilson-Jones angiosarcoma) BJD 169:204–206, 2013; Cutis 90:42–45, 2012; AD 148:683–685, 2012; BJD 163:225–227, 2010; JAAD 38:143–175, 1998; Cancer 77:2400–2406, 1996; BJD 160:456–458, 2009; facial edema at beginning of development JAAD 38:143–175, 1998; Cancer 59:1046–1057, 1987; facial edema and violaceous plaque covering

398 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 entire cheek AD 143:1602–1603, 2007; congenital fatal angiosarcoma Soc Ped Derm Annual Meeting, July 2005

ing sweat duct carcinoma (microcystic adnexal carcinoma) Ped Derm 25:38–42, 2008

Apocrine hamartoma – annular skin colored plaque of temple Ped Derm 24:346–347, 2007

Milia en plaque – face, eyelid, ears and ear lobes J Eur Acad Dermatol Venereol 14:47–49, 2000; Ped Derm 15:282–284, 1998

Basal cell carcinoma, including basal cell carcinoma mimicking rhinophyma AD 124:1077–1079, 1988; morpheaform basal cell carcinoma – personal observation

Neurilemmomas – linear array on forehead Clin Exp Dermatol 16:247–249, 1991

Basaloid follicular hamartoma (yellow plaque with milia) AD 129:915–917, 1993

Nevus sebaceus - yellow, skin-colored, or red plaque AD 135:637– 640, 1999

Blue nevus – plaque-type blue nevus Ann Plast Surg 35:326–329, 1995

Plasmacytosis – red plaques of face JAAD 49:1195–1196, 2003

Bowen’s disease CD4+/CD56+ hematodermic neoplasm (“blastic natural killer cell lymphoma”; blastic plasmacytoid dendritic cell neoplasm) – red brown facial plaque; vascular nodule of forehead Cutis 89:278–283, 2012; AD 146:1167–1172, 2010 Dermatofibrosarcoma protuberans Desmoplastic trichoepithelioma AD 131:211–216, 1995; annular facial plaque AD 132:1239–1240, 1996 Eccrine angiomatous nevus JAAD 29:274–275, 1993

Plexiform neurofibroma – personal observation

Porokeratosis – facial porokeratosis – annular red plaque AD 147:1097–1102, 2011; destructive facial porokeratosis JAAD 33:1045–1050, 1995 Seborrheic keratosis Squamous cell carcinoma Syringocystadenoma papilliferum AD 71:361–372, 1955 Trichoblastoma (trichoblastic fibroma) AD 137:219–224, 2001; AD 131:198–201, 1995 Trichoepithelioma JAAD 37:881–883, 1997

Eccrine porocarcinoma JAAD 27:306–311, 1992 Elastoma – bilateral, thickened furrowed plaques of the cheeks Aust J Dermatol 19:118–120, 1978

PARANEOPLASTIC

Epidermal nevus

Bazex syndrome

Epidermoid cyst, ruptured

Metastatic carcinoid – cutaneous paraneoplastic granulomatous reactions in metastatic carcinoid BJD 172:1451–1454, 2015

Follicular hamartoma (associated with myasthenia gravis) Clin Exp Dermatol 6:283–289, 1981 Hyperkeratotic lichen planus-like reactions combined with infundibulocystic hyperplasia AD 140:1262–1267, 2004 Inflammatory linear verrucous epidermal nevus (ILVEN) Kaposi's sarcoma Leiomyomatosis

Necrobiotic xanthogranuloma with paraproteinemia – yellow eyelid papules Ann Hematol 86:303–306, 2007; Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p. 143; Hautarzt 46:330–334, 1995; AD 128:94–100, 1992; JAAD 3:257–270, 1980; extensive facial plaque AD 146:957–960, 2010; with giant cell myocardial disease Mayo Clin Proc 72:1028– 1033, 1997; BJD 133:438–443, 1995

Lentigo maligna melanoma Leukemia cutis – acute lymphocytic leukemia – red plaque Cutis 75:54–56, 2005; granulocytic sarcoma (chloroma) Cutis 34:285– 287, 1984; acute myelogenous leukemia

PHOTOSENSITIVITY DISORDERS

Lichen planus-like keratosis

Actinic granuloma (annular elastolytic giant cell granuloma, Miescher's granuloma) Eur J Dermatol 9:647–649, 1999; Cutis 62:181–187, 1998; JAAD 1:413–421, 1979; AD 111:460–466, 1975

Lymphoma – red plaques of face especially eyebrow region – cutaneous T-cell lymphoma; pilotropic (follicular) CTCL – periauricular red plaques JAAD 62:418–426, 2010; AD 144:738–746, 2008; AD 138:191–198, 2002; cutaneous T-cell lymphoma NEJM 372:2437, 2015; lymphomatoid granulomatosis JAAD 27:872–876, 1992; B cell lymphoma; blastic natural killer cell lymphoma BJD 148:507– 515, 2003; primary cutaneous anaplastic large cell lymphoma AD 143:255–260, 2007; extranodal NK/T-cell lymphoma, nasal type – mimics facial cellulitis BJD 160:333–337, 2009; primary cutaneous follicular helper T-cell lymphoma – red papules, red plaques, scalp nodule, facial plaques AD 148:832–839, 2012

Actinic elastotic plaque Australas J Dermatol 30:15–22, 1989

Actinic lichen planus AD 135:1543, 1546, 1999 Actinic prurigo Actinic reticuloid JAAD 21:205–214, 1989 Chronic actinic dermatitis JAAD:21:205–214, 1989 Favre-Racouchot syndrome Cutis 60:145–146, 1997; AD 128:615– 616, 1992 Polymorphic light eruption

Lymphocytoma cutis Melanocytic nevus – congenital melanocytic nevus Melanoma Semin Oncol 2:5–118, 1975; desmoplastic melanoma JAAD 26:704–609, 1992 Metastatic carcinoma - prostate JAAD 53:744–745, 2005; gastric adenocarcinoma Cutis 76:194–196, 2005 Microcystic adnexal tumor – nasolabial area, upper lip, periorbital plaque; skin-colored to yellow plaque AD 143:791–796, 2007; Sem Cut Med Surg 21:159–165, 2002; Derm Surg 27:979–984, 2001; South Med J 87:259–262, 1994; JAAD 29:840–845, 1993; scleros-

PRIMARY CUTANEOUS DISEASE Acne rosacea (granulomatous); gnatophyma (hypertrophy of the chin) JAAD 55:165–166 2006 Alopecia mucinosa (follicular mucinosis) AD 143:921–932, 2007; AD 138:182–189, 2002; Ped Derm 19:33–35, 2002; Derm 197:178–180, 1998; AD 125:287–292, 1989; JAAD 10:760–768, 1984 Annular atrophic plaques of the face AD 100:703–716, 1969

Facial Plaques, Scarring and Non-scarring Atopic dermatitis Dowling-Degos disease Elastosis perforans serpiginosa – annular facial plaques AD 145:931–936, 2009 Eosinophilic angiocentric fibrosis (variant of granuloma faciale) – red facial plaque with saddle nose deformity BJD 152:574–576, 2005; Histopathology 9:1217–1225, 1985 Erythrokeratoderma variabilis SkinMed:Dermatology for the Clinician:231–232, July, Aug 2004; Ped Derm 12:21–23, 1995 Granuloma annulare – personal observation Granuloma faciale Int J Dermatol 36:548–551, 1997; AD 129:634– 635, 637, 1993; granuloma faciale with eosinophilic angiocentric fibrosis – red plaque of nose AD 148:755–760, 2012 Hailey-Hailey disease – vegetative multilobulated malodorous friable plaques of cheek JAAD 65:223–224, 2011 Keratosis lichenoides chronica JAAD 28:870–873, 1993 Kimura’s disease Cutis 66:201–204, 2000 Lichen planus, hypertrophic

399

edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks and arms, chondritis with progressive ear and saddle nose deformities, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, splenomegaly, protuberant abdomen JAAD 62:489–495, 2010 Haber's syndrome – rosacea-like KID syndrome – keratosis, ichthyosis, deafness syndrome – fixed orange, symmetrical hyperkeratotic plaques of scalp, ears, and face with perioral rugae; aged or leonine facies; erythrokeratoderma-like; later hyperkeratotic nodules develop Ped Derm 17:115–117, 2000; Ped Derm 13:105–113, 1996 Melkersson-Rosenthal syndrome (facial edema) Nijmegen breakage syndrome – autosomal recessive; immunodeficiency, growth retardation, characteristic facies and cutaneous granulomas, predisposition to cancer AD 144:418–419, 2008

Mid-dermal elastolysis (resembles eosinophilic pustular folliculitis) JAAD28:938–942, 1993

NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic self-limiting fever, polyarthritis, polyarthralgia, red plaques of face and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013

Miescher’s granuloma – personal observation

Rombo syndrome

Normolipemic papuloeruptive cutaneous xanthomatosis (red-yellow plaques of face) Ped Derm 26:360–362, 2009; J Dermatol 18:235– 239, 1991; AD 122:1294–1297, 1986

SAVI – (STING (stimulator of interferon genes)-associated vasculopathy) – progressive digital necrosis, swelling of fingers, amputation of several digits, violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of arms and legs JAAD 74:186–189, 2016

Lichen sclerosus et atrophicus Lichen simplex chronicus – personal observation

Ofuji’s disease (eosinophilic pustular folliculitis) – red plaque with papules and pustules JAAD 46:827–833, 2002; Ann DV 124:540– 543, 1997; JAAD 29:259–260, 1993; sterile papules, pustules, and plaques of face, trunk, arms, palms, soles JAAD 23:1012–1014, 1990; JAAD 14:469–474, 1986 Palpable migratory arciform erythema J Drugs Dermatol 13:1288– 1289, 2014; Hum Pathol 5:25–43, 1974 Pityriasis rosea Pseudolymphoma – red plaques of face AD 148:372–374, 2012 Psoriasis Rhinophyma Scleredema Seborrheic dermatitis – personal observation Transient acantholytic dermatosis Cutis 38:48–49, 1986 Urticaria, chronic – personal observation

PSYCHOCUTANEOUS DISEASE Factitial dermatitis – red facial plaque Ped Derm 24:327–329, 2007

SYNDROMES Adult onset asthma with periocular xanthogranuloma Ophthalmol Plast Reconstr Surg 29:104–108, 2013; AD 147:1230–1231, 2011; Br J Ophthalmol 90:602–608, 2006 Anhidrotic ectodermal dysplasia Ataxia telangiectasia – red plaque of face; cutaneous granuloma of ataxia telangiectasia JAAD 65:676–677, 2011; BJD 153:194–199, 2005; AD 134:1145–1150, 1998 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature – annular erythematous

Sweet's syndrome with or without pustules Cutis 89:121–124, 2012; Ped Derm 29:38–44, 2012; Ped Derm 27:208–209, 2010; Cutis 71:469–472, 2003; JAAD 40:838–841, 1999; AD 134:625–630, 1998; JAAD 31:535–536, 1994; BJD 76:349–356, 1964; granulomatous plaque BJD 80:8906–810, 1968; chronic recurrent Sweet’s syndrome of myelodysplasia – pustules, plaques, and papules AD 142:1170–1176, 2006; histiocytoid Sweet’s syndrome – red plaques of face and trunk JAAD 61:882–884, 2009 Tuberous sclerosis – forehead plaque JAAD 57:189–202, 2007; JAAD 49:698–705, 2003; JAAD 45:731–735, 2001; Derm Surg 27:486–488, 2001; BJD 147:337–342, 2002; J Child Neurol 13:624–628, 1998; BJD 135:1–5, 1996; AD 132:1107, 1110, 1996; JAAD 32:915–935, 1995; J Clin Neurol 7:221–224, 1992; Ped Clin North Amer 38:991–1017, 1991; Arch Dis Child 62:292–293, 1987; S Med J 75:227–228, 1982 Wallenberg’s syndrome Wells' syndrome AD 125:1625–1626, 1989

TRAUMA Fat necrosis of the newborn – due to forceps injury Textbook of Neonatal Dermatology, p. 421, 2001 Cold panniculitis (neonatal) (Haxthausen’s disease) JAAD 33:383– 385, 1995; Burns Incl Therm Inj 14:51–52, 1988; AD 94:720–721, 1966; BJD 53:83–89, 1941; popsicle panniculitis; localized cold urticaria of face – red facial plaques Ped Derm 27:266–269, 2010; BJD 132:666–667, 1995; J Allergy Clin Immunol 88:682, 1991; J Allergy Clin Immunol 86:272–273, 1990

400 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Islamic prayer nodules – on foreheads of Shi’ite Muslims Int J Dermatol 20:133, 1981 Scarring JAAD 25:761–766, 1991

VASCULAR Acute hemorrhagic edema of infancy AD 139:531–536, 2003 Arteriovenous hemangioma (cirsoid aneurysm or acral arteriovenous tumor) – associated with chronic liver disease BJD 144:604– 609, 2001

CONGENITAL LESIONS Congenital vesicular and erosive dermatosis with supple and reticulated scarring – facial scars at birth which improve with time JAAD 69:909–915, 2013; AD 121:361–367, 1985 Neonatal acne with scarring – personal observation Neonatal lupus erythematosus with RNP antibodies – varicelliform erosions and facial scars; no cardiac symptoms Ped Derm 30:416–423, 2013

Arterio-venous malformation – personal observation

DRUG REACTIONS

Congenital plaque type glomuvenous malformations – glomulin gene on 1p21; loss of function mutation; red plaque of face AD 142:892–896, 2006

Acneiform – drug-induced acne

Granulomatosis with polyangiitis – ulcerated annular plaque of forehead Ped Derm 33:551–552, 2016

Naproxen – photosensitivity in children leading to linear scars from minor trauma J Pediatr 125:819–822, 1994

Infantile hemangioma, including hemangioma of lower lateral cheek associated with airway obstruction; zosteriform infantile hemangioma of face BJD 169:1252–1256, 2013; Ped Derm 30:151–154, 2013; JAAD 48:477–493, 2003; large facial hemangiomas of PHACES syndrome JAAD 48:477–493, 2003; periocular hemangioma – red facial plaque JAAD 55:614–619, 2006

INFECTIONS AND INFESTATIONS

Infantile hemangioma of the beard region associated with subglottic hemangioma Seminars Cut Med Surg 35:108–116, 2016

Botryomycosis – granulomatous reaction to bacteria with granule formation; single or multiple abscesses of skin and subcutaneous tissue break down to yield multiple sinus tracts; small papule; heals with atrophic scars; extremities, perianal sinus tracts, face Int J Dermatol 22:455–459, 1983; AD 115:609–610, 1979

Lymphedema, chronic Malignant angioendotheliomatosis PHACES syndrome – large facial infantile hemangioma; posterior fossa malformations, cervicofacial hemangiomas, often segmental, arterial anomalies, cardiac defects, eye anomalies, and sternal clefting or supraumbilical raphe; Dandy-Walker malformation (posterior fossa cyst with hypoplasia of the cerebellar vermis; cystic dilatation of the fourth ventricle leading to hydrocephalus and increased head circumference) BJD 173:242–246, 2015; Cutis 92:113, 119–120, 2013; Ped Derm 26:730–734, 2009; Ped Derm 23:476–480, 2006; Neuroradiology 16:82–84, 1978; association with hearing loss AD 146:1391–1396, 2010 Takayasu's arteritis – LE-like Circulation 35:1141–1155, 1967 Tufted angioma

Actinomycosis, cervicofacial – nodule of cheek or submaxillary area; board-like induration; multiple sinuses with puckered scarring; sulfur granules discharged Cutis 60:191–193, 1997; Arch Int Med 135:1562–1568, 1975 Anthrax Ped Derm 19:36–38, 2002

Brown recluse spider bite Cowpox Br J Plast Surg 3:348–350, 2000 Cryptococcosis – mimicking a keloid Dermatology 202:78–79, 2001 Dental sinus, healed – personal observation Ecthyma – personal observation Herpes simplex; intrauterine infection J Pediatr 110:97–101, 1987; recurrent herpes simplex infection – personal observation Herpes zoster Leishmaniasis – chronic lupoid leishmaniasis AD 132:198–202, 1996; chronic hyperpigmentation and irregular cribriform scars Rhinoscleroma

FACIAL SCARS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Brunsting-Perry cicatricial pemphigoid – herpetiform plaques with scarring Lancet 381:320–332, 2013; J Dermatol 38:887–892, 2011; AD 75:489–501, 1957; alopecic scalp scars

Smallpox (variola) Int J Epidemiol 9:335–340, 1980 Sycosis barbae – deep staphylococcal folliculitis Dermatol Wochenschr 152:153–167, 1966 Syphilis, congenital – linear scar Actas Dermosifiliogr 56:203–206, 1965 (Spanish); tertiary nodular syphilide with central scarring Varicella Br J Plast Surg 26:344–345, 1973

Hyper IgE syndrome – pitted facial scars JAAD 54:855–865, 2006

INFILTRATIVE LESIONS

Lupus erythematosus – discoid lupus erythematosus NEJM 269:1155–1161, 1963; lupus profundus Acta DV 80:373–375, 2000; discoid lupus with annular atrophic plaques of face, neck, behind ears AD 112:1143–1145, 1976; lupus profundus; disfiguring scars Ped Derm 32:419–420, 2015

Nodular colloid milium – mimics keloid Cosmetic Dermatol 16:e45–47, 2017

Mixed connective tissue disease

INFLAMMATORY Edematous scarring vasculitic panniculitis – hydroa vacciniformelike lesions with vesicles, deep ulcers, varicelliform scars JAAD 32:37–44, 1995

Facial Scars Hidradenitis suppurativa – personal observation Pyoderma gangrenosum BMJ 316:52–53, 1998 Sarcoid – scar sarcoidosis in pseudofolliculitis barbae Mil Med 156:369–371, 1991 Superficial vegetating pyoderma – personal observation

401

Hydroa vacciniforme BJD 144:874–877, 2001; BJD 144:874–877, 2001; Dermatology 189:428–429, 1994; JAAD 25:892–895, 1991; AD 114:1193–1196, 1978; hydroa vacciniforme (Epstein-Barr virus-related) – red macules progress to tender papules or vesiculopapules, hemorrhagic vesicles or bullae, umbilication and crusting; pock-like scars; edema of cheeks, eyelids, ears, and lips AD 142:587–595, 2006

METABOLIC DISEASES Porphyria – congenital erythropoietic porphyria – scarring mutilation of nasal tip, ears, eyelids, and facial scarring; blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, keratoconjunctivitis, cataracts JAAD 67:1093– 1110, 2012; AD 141: 1575–1579, 2005; AD 128:1243–1248, 1992; erythropoietic protoporphyria – linear facial scars; porphyria cutanea tarda Ped Derm 45:320–324, 1987; JAAD 27:896–900, 1992; familial porphyria cutanea tarda; variegate porphyria

PRIMARY CUTANEOUS DISEASES Acne excoriee des jeunes filles Int J Derm 33:846–848, 1994; Clin Exp Dermatol 8:65–68, 1983 Acne necrotica varioliformis (necrotizing lymphocytic folliculitis) AD 132:1367, 1370, 1996; JAAD 16:1007–1014, 1987 Acne, neonatal Acne rosacea fulminans (pyoderma faciale) Cutis 92:29–32, 2013 Acne vulgaris

NEOPLASTIC Basal cell carcinoma – keloidal basal cell carcinoma BJD 134:953– 957, 1996; morpheaform basal cell carcinoma – personal observation Desmoplastic trichoepithelioma – scar-like appearance Eccrine syringomatous carcinoma – facial scar-like lesion JAMADerm 151:1034–1036, 2015 Keloids Arch Otolaryngol Head Neck Surg 123:397–400, 1997 Multiple keratoacanthomas Lymphoma – angiocentric cutaneous T cell lymphoma of childhood (hydroa-like lymphoma) of Latin America and Asia BJD 140:715– 721, 1999; JAAD 38:574–579, 1998; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 69:112–119, 2013;

Acute febrile ulcerative acne conglobate (acne fulminans, acne maligna) Anetoderma of Jadassohn – personal observation Atrophia maculosa varioliformis cutis – linear, varioliform scars BJD 153:821–824, 2005; Ped Derm 18:230–233, 2001; Acta DV 75:252, 1995; JAAD 30:837–840, 1994; JAAD 21:309, 1989; BJD 115:105– 109, 1986; AD 64:59–61, 1951; J Cutan Dis 36:285–288, 1918 Atrophoderma vermiculata Cutis 59:337–340, 1997 Epidermolysis bullosa – dominant and recessive dystrophic Focal facial dermal dysplasia – scar-like depressions of face JAAD 27:575–582, 1992 Keratosis pilaris rubra atrophicans facei Lupus miliaris disseminate faciei (granulomatous rosacea) Dermatol Online J Aug 17, 2014 Pili multigemini – along jawline; with inflammatory nodules; scars Pityriasis lichenoides et varioliformis acuta, including febrile ulceronecrotic Mucha-Habermann disease BMJ Case Rep Oct 14, 2013

variant of extranodal NK/T cell lymphoma, nasal type/ CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of hands, subcutaneous nodules; systemic manifestations; occurs on both sun-exposed and non-sun-­exposed skin Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998

Reactive perforating collagenosis – personal observation

Melanoma, desmoplastic

Factitial dermatitis – linear lesions and linear scars JAAD 1:391– 407, 1979

Piloleiomyoma – mimics post-acne scarring Cutis 73:335–337, 2004 Porokeratosis – destructive facial porokeratosis JAAD 33:1049– 1050, 1995

Ulerythema oophryogenes

PSYCHOCUTANEOUS DISEASE Delusions of parasitosis

Neurotic excoriations – personal observation

SYNDROMES PHOTODERMATOSES Actinic prurigo (polymorphic light eruption of American Indians) – linear and pitted facial scars JAAD 67:1093–1110, 2012; JAAD 44:952–956, 2001; Australas J Dermatol 42:192–195, 2001; Photodermatol Photoimmunol Photomed 15:183–187, 1999; Int J Dermatol 34:380–384, 1995; JAAD 26:683–692, 1992; JAAD 5:183–190, 1981; Clin Exp Dermatol 2:365–372, 1977; familial, in North American Indians Int J Dermatol 10:107–114, 1971; in Caucasians BJD 144:194–196, 2001; occurrence in non-Indians JAAD 34:612–617, 1996; Southeast Asian Photodermatol Photoimmunol Photomed 9:225–228, 1992

Anhidrotic ectodermal dysplasia – carrier – X-linked recessive – personal observation Atypical trigeminal trophic syndrome Clin Exp Dermatol 44:225– 228, 2019 Congenital insensitivity to pain with anhidrosis Cutis 60:188–190, 1997 Dowling-Degos syndrome – pitted perioral scars AD 114:1150– 1157, 1978 Ehlers-Danlos syndrome types I, II, and III – linear scars – widened atrophic scars Medicine 98:e17138, 2019

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Facial focal dermal dysplasias BJD 135:607–608, 1996  Autosomal dominant focal facial dermal dysplasia without other facial anomalies – oval symmetrical scarred areas on temples, cheeks, rim of fine lanugo hairs BJD 84:410–416, 1971  Autosomal recessive focal facial dermal dysplasia without other facial anomalies JAAD 27:575–58, 1992  Focal facial dermal dysplasia with other facial anomalies (Setleis syndrome) – leonine aged facies with absent eyelashes, eyebrows, puckered periorbital skin, scar-like defects of temples Clin Dysmorph 5:249–253, 1996; JAAD 27:575–582, 1992; AD 110:615–618, 1974

FACIAL ULCERS

Goltz's syndrome (focal dermal hypoplasia) – icepick facial scars NY State Dent J 67:30–32, 2001

Immunodeficiency disease with RAG mutations and granulomas – ulcers of the face and extremities NEJM 358:2030–2038, 2008

Haber’s syndrome JAAD 40:462–467, 1999

Lupus erythematosus – discoid lupus erythematosus JAAD 48:S89–91, 2003; lupus profundus Lupus 10:514–516, 2001; neonatal LE – personal observation

Lesch-Nyhan syndrome Lipoid proteinosis – crusted red papules of face heal with scarring Ped Derm 22:266–267, 2005; BJD 151:413–423, 2004; JID 120:345–350, 2003; Hum Molec Genet 11:833–840, 2002; JAAD 39:149–171, 1998; Arch Pathol Anat 273:286–319, 1929 Midface toddler excoriation syndrome (MITES) – linear excoriations; mutation in PR domain containing protein 12 (PRDM12) Nevoid basal cell carcinoma syndrome – odontogenic cyst excision scar – personal observation Reticulolinear aplasia cutis congenita of the face and neck – Xp deletion syndrome, MIDAS (microphthalmia, dermal aplasia, sclerocornea), MLS (microphthalmia and linear skin defects), and Gazali-Temple syndrome; lethal in males; residual facial scarring in females, short stature, organ malformations BJD 138:1046–1052, 1998 Smith-Magonis syndrome – self-injurious behavior and scars Ped Derm 32:337–341, 2015 Tricho-odonto-onychial ectodermal dysplasia – perioral atrophic scars AD 122:1047–1053, 1986 Xeroderma pigmentosum

TOXINS Dioxin – varioliform scarring due to dioxin exposure JAAD 19:812– 819, 1988

TRAUMA Bites – animal and human Burns – thermal, electrical

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Brunsting-Perry cicatricial pemphigoid AD 131:580–585, 1995 Chronic granulomatous disease – including perioral ulcers AD 103:351–357, 1971 Cicatricial pemphigoid of childhood Dermatitis herpetiformis – personal observation

Pemphigus vulgaris – facial erosions AD 110:862–865, 1974 PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAMADerm 151:627–634, 2015 Scleroderma – CREST syndrome

CONGENITAL LESIONS Reticulolinear aplasia cutis congenita of the face and neck – syndromes linked to Xp22 BJD 138:1046–1052, 1998

DEGENERATIVE DISEASES Trigeminal trophic syndrome (Wallenberg’s syndrome) – diabetes mellitus, posterior inferior cerebellar artery stroke, amyloidosis, sarcoidosis, sickle cell disease, vasculitis, demyelinating disease, syringobulbia, idiopathic; ulcer of ala nasi which expands to involve cheek and upper lip JAAD 74:215–228, 2016; AD 148:641–646, 2012; AD 144:984–986, 2008; Cutis 81:419–420, 2008; AD 142:941–942, 2006; AD 141:796–798, 2005; Mayo Clin Proc 72:543–545, 1997; Cancer 70:877–881, 1992; Oral Surg 69:153– 156, 1990; CMAJ 29:492–496, 1933; ulcer of nose AD 141:897– 902, 2005; Mayo Clin Proc 72:543–545, 1997; Clin Exp Dermatol 10:485–490, 1985; Dt X Nervenheilk 19:227–231, 1901; tuberculoid leprosy Lepr Rev 83:102–112, 2012

Facial scarification and tattooing Cutis 60:197–198, 1997 Intense pulsed-light therapy JAAD 73:15–24, 2015 Laser therapy Mechanical trauma Radiation dermatitis

DRUG ERUPTIONS Nicorandil – ulcer of forehead and nasal columella BJD 171:662– 663, 2014

Trapshooter’s marks

EXOGENOUS AGENTS VASCULITIS Granulomatosis with polyangiitis – personal observation Granulomatous vasculitis in rheumatoid disease – facial rash with scarring Ann Rheum Dis 45:75–77, 1986

Cocaine abuse – ulceronecrotic nasoparanasal lesions; cocaine sniffing ulcer AD 143:653–658, 2007; NEJM 352:609–615, 2005; Cutis 65:73–76, 2000; mimicking midline granuloma Eur Arch Otorhinolaryngol 255:446–447, 1998; JAAD 32:286–287, 1995

Facial Ulcers Nasal alloplastic implant – infection and extrusion – nasal tip ulceration JAAD 44:362–364, 2001 Silicone injection, subcutaneous JAAD 34:849–852, 1996

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Histoplasmosis in AIDS or with Hyper IgM syndrome BJD 133:472– 474, 1995; Ped Derm 12:235–238, 1995; ecthyma-like Dermatol Online J April 15, 2009; punched out ulcers in HIV disease Int J Dermatol 40:518–521, 2001 Impetigo

INFECTIONS AND INFESTATIONS Acanthamoeba in AIDS JAAD 42:351–354, 2000; AD 131:1291– 1296, 1995; JAAD 26:352–355, 1992; periorbital ulcer Am J Trop Med Hyg 35:69–71, 1986 AIDS – facial eschar; excoriations, post-herpes zoster Anthrax – Bacillus anthracis; swollen eyelids; malignant pustule; painless ulcer with vesicular lesions; face, neck, hands, fingers, arms, foot, knee; starts as painless erythema evolving into papule then into multiple vesicles or bulla on red base; then ulcer with hemorrhagic crust (eschar) with edema and erythema with small vesicles; edema of surrounding skin; takes six weeks to heal; edema of eyelids, lips, perioral area; slaughtering or milking of ill cows, sheep, or goats; handling of raw meat Ped Derm 27:600–606, 2010; Ped Derm 18:456–457, 2001; Cutis 67:488–492, 2001; Clin Inf Dis 19:1009–1014, 1994; Br J Opthalmol 76:753–754, 1992; Cutis 48:113–114, 1991; Cutis 40:117–118, 1987; J Trop Med Hyg 89:43–45, 1986; Bol Med Hosp Infant Mex 38:355–361, 1981; preseptal cellulitis and cicatricial ectropion Acta Ophthalmol Scand 79:208–209, 2001; Br J Opthalmol 76:753–754, 1992; Ophthalmic Physiol Opt 10:300–301, 1990 Aspergillosis Bejel – destructive midline lesions of face Blastomyces dermatitidis Neurology 68:1746–1747, 2007; Clin Inf Dis 33:1706, 1770–1771, 2001 Buruli ulcer (Mycobacteria ulcerans subspecies shinshuense) – facial ulcer; ulcerated red plaque of face JAMA Derm 150:64–67, 2014 Chancriform pyoderma (Staphylococcus aureus) – ulcer with indurated base; eyelid, near mouth, genital AD 87:736–739, 1963

Leishmaniasis, Desert sore (Veldt sore) Clin Dermatol 38:152–159, 2020; JAAD 56:612–616, 2007; Int J Derm 33:260–265, 1994; ulcerated plaque of chin – New World leishmaniasis AD 146:789– 794, 2010; multiple ulcerated plaques – New World leishmaniasis Ped Derm 24:657–658, 2007; ulcerated nodule of buttock; L. Mexicana, L. venezuelensis; L. amazonensis, L. braziliensis. L. peruviana, L. guyanensis, L. panamensis; lip ulcers, crusted ulcer of face; ulcers of nasal septum, palate, lips, pharynx, larynx can develop months to years after initial infection Leprosy JAMADerm 152:333–334, 2016; Int J Lepr Other Mycobact Dis 59:479–480, 1991; Lucio’s phenomenon An Bras Dermatol 88 (suppl1)93–96, 2013 Mucormycosis – destructive midline lesions of face Int J Dermatol 58:285–287, 2019; J Oral Maxillofac Pathol 18:460–463, 2014;AD 133:249–251, 1997; slowly progressive cutaneous rhinofacial and pulmonary mucormycosis due to Mucor irregularis Clin Inf Dis 56:993–995, 2013 Mycobacterium flavescens – ulcerated nodule following eyebrow piercing Ped Derm 25:219–222, 2008 Mycobacterium tuberculosis – tuberculous chancre – facial ulcer; ragged undermined ulcer with granular hemorrhagic base; face; paronychia; surrounded by lupoid nodules; traumatic wounds, surgical wounds Rev Bras Oftel 23:183–192, 1964; mouth to mouth respiration NEJM 273:1035–1036, 1965; tuberculous abscess; ulcer of the nose Ann DV 110:731–732, 1983; lupus vulgaris – destructive midline lesion of face Myiasis – destructive midline lesions of face (wound myiasis); Old World screwworm (Chrysomya bezziana) JAAD 58:907–926, 2008; oculofacial myiasis (Lucilia sericata) JAAD 61:169–170, 2009

Chromomycosis (Fonsecaea pedrosoi) Indian J Dermatol 51:576– 578, 2012

Nasopharyngeal mutilation

Coccidioidomycosis JAAD 77:197–218, 2017; SMJ 77:1464–1465, 1984

Noma (cancrum oris) – associated with malnutrition, unsafe drinking water, poor sanitation, poor oral health; Fusobacterium necrophorum, Prevotella intermedium Am J Trop Med Hyg 60:150–156, 1999; Cutis 39:501–502, 1987; J Maxillofac Surg 7:293–298, 1979

Cowpox Br J Plast Surg 53:348–350, 2000 Cryptococcosis Eur J Dermatol 20:657–658, 2010; AD 122:825– 826, 1986; Cryptococcus gattii Mycopathologia 161:235–238, 2006 Cytomegalovirus – vegetative ulcer of face BJD 170:223–224, 2014 Dental sinus Cutis 70:264–267, 2002 Ecthyma – personal observation Ecthyma gangrenosum JAAD 29:104–116, 1993; AD 126:529, 532, 1990; Am J Med 80:729–734, 1986; pseudomonas – simulating cancrum oris Afr J Lab Med 7:756, 2018 Frontal sinusitis with forehead abscess – personal observation Fusarium solani, disseminated; of sinuses; eschar of bridge of nose JAAD 47:659–666, 2002 Glanders – Pseudomonas mallei – cellulitis which ulcerates with purulent foul-smelling discharge, regional lymphatics become abscesses; nasal and palatal necrosis and destruction; metastatic papules, pustules, bullae over joints and face, then ulcerate; deep abscesses with sinus tracts occur; polyarthritis, meningitis, pneumonia Herpes simplex, chronic; eczema herpeticum; in AIDS – personal observation Herpes zoster – dysesthesia following herpes zoster – personal observation

Necrotizing fasciitis – destructive midline lesions of face

Paracoccidioidomycosis (disseminated) (South American blastomycosis) NEJM 371:1756–1758, 2014; in AIDS JAAD 53:931–951, 2005; JAAD 20:854–855, 1989; destructive midline lesions of face Pseudomonas sepsis, including noma neonatorum (Pseudomonas of oronasal area and eyelids in infants) Lancet 2:289–291, 1978 Rhinoscleroma – destructive midline lesions of face Rhinosporidiosis – destructive midline lesions of face Sporotrichosis Ped Derm 24:369–372, 2007; Cutis 69:439–442, 2002; in AIDS JAAD 21:1145–1147, 1987; eschar of forehead – fixed cutaneous neonatal sporotrichosis Ped Derm 26:563–565, 2009 Subcutaneous phaeohyphomycosis – Corynespora casslicol (plant pathogen of leaf spotting disease) in CARD9 deficiency BJD 174:176–179, 2016 Syphilis, primary, secondary – noduloulcerative (malignant lues) AD 113:1027–1032, 1997; Clin Inf Dis 25:1343, 1447, 1997; tertiary AD 123:1707–1712, 1987; gumma Tularemia, ulceroglandular NEJM 374:573–581, 2016 Yaws – destructive midline lesions of face

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INFLAMMATORY DISORDERS

PARANEOPLASTIC DISORDERS

Acquired lacrimal sac fistula due to dacryocysitis – ulcers around medial canthus BJD 168:1348–1350, 2013

Necrobiotic xanthogranuloma with paraproteinemia

Eosinophilic ulcer Erythema multiforme, minor, major (Stevens-Johnson syndrome)

PRIMARY CUTANEOUS DISEASES

Lethal midline granuloma (cephalic granulomatosis with polyangiitis) – tip of nose ulcer (Stewart type) Am J Otolaryngol 31:104–109, 2010; AD 118:52–4, 1982

Acne excoriee des jeunes filles Int J Derm 33:846–848, 1994; Clin Exp Dermatol 8:65–68, 1983; in obsessive compulsive disorder JAAD 76:779–791, 2017

Malignant pyoderma of the head and neck AD 123:371–375, 1987; JAAD 15:1051–1052, 1986; papulopustules, skin ulcers, violaceous nodules with central necrosis, tongue, pharyngeal, and nasal ulcers AD 146:102–103, 2010; AD 98:561–576, 1968

Acne fulminans AD 121:91–93, 1985

Pyoderma gangrenosum JAMADerm 155:79–84, 2018; Clin Inf Dis 67:477–479, 2018; AD 144:817–818, 2008; Cutis 69:427–430, 2002; Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988; ulcer of eyelid JAMADerm 152:491–492, 2016 Sarcoidosis AD 133:215–219, 1997 Superficial vegetating (granulomatous) pyoderma JAAD 48:456– 460, 2003; Dermatol 202:155–157, 2001

METABOLIC DISEASES Cryoglobulinemia JAAD 25:21–27, 1991 Necrobiosis lipoidica diabeticorum – ulcerated facial plaque AD 130:1433–1436, 1994; Acta DV 58:276–277, 1978 Pellagra – facial crusting JAAD 21:1–30, 1989 Porphyria cutanea tarda with calcinosis cutis Med Clin NA 64:807827, 1980; Am J Med 277:286, 1979

NEOPLASTIC Basal cell carcinoma BJD 171:431–433, 2014; J Drugs in Dermatol 13:601–606, 2014Acta Pathol Mibrobiol Scand 88A:5–9, 1980 Blastic plasmacytoid dendritic cell neoplasm Clin Exp Dermatol 44:221–224 2019 Intranasal carcinoma Lymphoma – cutaneous T-cell lymphoma BJD 163:884–885, 2010; Epstein-Barr virus-associated hydroa vacciniforme-like cutaneous lymphoma; variant of extranodal NK/T cell lymphoma, nasal type/ CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of hands, subcutaneous nodules; systemic manifestations; occurs on both sun-exposed and non-sun-exposed skin Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998 (angiocentric CTCL of childhood (hydroa-like lymphoma) of Latin America and Asia JAAD 38:574–579, 1998); angiocentric T-cell lymphoma – necrotic facial ulcers Cutis 77:310– 312, 2006; lymphomatoid granulomatosis JAAD 23:334–337, 1990; lethal midline granuloma; subcutaneous panniculitis-­like T-cell lymphoma BJD 148:516–525, 2003; pyogenic lymphoma – primary cutaneous neutrophil-rich CD30+ anaplastic large-cell lymphoma BJD 148:580–586, 2003 Lymphomatoid papulosis Cutis 100:297–298, 2017; Dermatol Online J March 30, 2006 Melanoma Semin Oncol 2:5–118, 1975

Acute parapsoriasis – febrile ulceronecrotic Mucha-Habermann disease BMJ Case Rep Oct 14, 2013 Ectodermal dysplasia Epidermolysis bullosa, junctional – facial erosions – JAAD 17:246– 50, 1987 Erosive pustular dermatosis of the scalp and nonscalp JAAD 57:S11–14, 2007 Hydroa vacciniforme – vesiculopapular eruption of face; crusted papules, necrosis, facial ulcers BJD 173:801–805, 2015 Kyrle's disease

PSYCHOCUTANEOUS DISEASES Delusions of parasitosis Hautarzt 39:675–676, 1988 Factitial dermatitis JAAD 76:779–791, 2017; Ped Derm 32:604–608, 2015; Cutis 84:247–251, 2009; JAAD 40:802–804, 1999; paraoral ulcers Oral Surg Oral Med Oral Pathol 64:259–263, 1987 Neurotic excoriations

SELF-MUTILATION Hereditary sensory neuropathy – five types Ped Derm 11:231–236, 1994  Midface toddler excoriation syndrome (MITES) (congenital insensitivity to pain) – autosomal recessive biallelic mutation in PRDM12 Ped Derm 37:345–346, 2020; BJD 179:1135–1140, 2018; Proc Roy Acad Med Ireland Dermatol Meeting 5 Dec 2014   Congenital sensory neuropathy with anhidrosis   Congenital sensory radicular neuropathy   Familial dysautonomia   Hereditary sensory radicular neuropathy

SYNDROMES Amniotic band syndrome Ectodermal dysplasias with mid-facial clefting JAAD 27:249–256, 1992   AEC syndrome   EEC syndrome   Rapp-Hodgkin ectodermal dysplasia Dysplasia epiphysealis hemimelica (Trevor disease, tarsomegaly) Familial chilblain lupus – paronychia, acral erythema, acral papules, necrotic ulcers, facial ulcers, mutilation of fingers, ear lesions; mutation of exonuclease III domain of 3’ repair exonuclease 1 (TREX1) JAMADerm 151:426–431, 2015

Merkel cell tumor

Laryngo-onycho-cutaneous syndrome (Shabbir’s syndrome, LOGIC syndrome) – facial erosions and ulcers, hoarseness, nail dystrophy; N-terminal deletion in laminin 3 alpha isoform Derm Clinics 28:211– 222, 2010; Clin Dysmorphol 1:3–15, 1992; Biomedica 2:15–25, 1986

Squamous cell carcinoma Derm Surg 28:268–273, 2002

Nevoid basal cell carcinoma syndrome BJD 174:68–76, 2016

Metastasis – oral squamous cell carcinoma spreading onto face JAAD 22:19–26, 1990

Prader-Willi syndrome

Facies

TRAUMA Bullet entry/exit wound Coma bullae Electrical cord burn – personal observation Post-surgical Pressure necrosis due to continuous positive pressure ventilation Ped Derm 29:45–48, 2012 Radiation necrosis Rat bites AD 148:1209–1210, 2012

VASCULAR Cutaneous polyarteritis nodosa Granulomatosis with polyangiitis – acneiform facial and truncal lesions with crusted necrotic papules, ulcers; palpable purpura JAAD 72:859–867, 2015; AD 136:171–172, 2000; Cutis 64:183– 186, 1999 Temporal arteritis – bilateral forehead necrosis with linear eschars JAAD 63:343–344, 2010

405

ICF syndrome (immunodeficiency, centromeric instability-facial anomalies) – autosomal recessive; variable immune deficiency, mental retardation, chromosomal instability, facial dysmorphism Am J Med Genet 66:378–398, 1996 Job’s syndrome coarse facial features – prominent forehead, deep set eyes, broad nasal bridge, wide fleshy nasal tip, mild prognathism, facial asymmetry; STAT 3 mutation Scleroderma STAT5b deficiency – dwarfism, facial dysmorphism, high pitched voice BJD 178:335–349, 2018 X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with unswept hair, flared eyebrows; female carriers display blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

DRUGS Coumarin embryopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 224–225 DRESS syndrome – facial edema, erythema and periorificial pustules and crusts

FACIES Genetic Skin Disorders, Second Edition, 2010

 UTOIMMUNE DISEASE AND DISORDERS A OF IMMUNE DYSREGULATION Aicardi-Goutieres syndrome – autosomal recessive; type 1 interferonopathy; neurodegenerative disease; mutation (TREX1;AGS1); mutation (SAMHD1;AGS5); mutation (AGS2–4); mutation in (AGS6); mutation in (AGS7); chilblain-like lesions; acrocyanosis; red periungual lesions; red earlobes; livedo reticularis, blueberry muffin baby; congenital encephalopathy with developmental delay; microcephaly; narrow facial features; seizures, spasticity, dystonic posturing Ped Derm 33:602–614, 2016 CEDNIK syndrome – autosomal recessive; cerebral dysgenesis, neuropathy, ichthyosis, keratoderma, microcephaly, facial dysmorphism including prominent nasal tip, flat broad nasal root, small chin, low set ears; absent dermatoglyphics, deafness Ped Derm 36:372–376, 2019; Am J Hum Genet 77:242–251, 2005 Chronic hypothyroidism – asymmetric brachycephaly, dysplastic ears, hypertelorism, epicanthal folds, broad nasal root Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 186–187 Dermatomyositis erythema at base of nares, scalp, face, heliotrope Hyper IgE syndrome (Job’s syndrome) (Buckley’s syndrome) – dermatitis of face, scalp, axillae, and groin; recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract; papular, pustular; furunculosis; growth failure; STAT3 mutations Clin in Dermatol 23:68–77, 2005; J Pediatr 141:572–575, 2002; NEJM 340:692–702, 1999; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983; Lancet 1:1013–1015, 1966 Ped Derm 30:621–622, 2013; NEJM 357:1608–1619; JAAD 54:855–865, 2006; AD 140:1119–1125, 2004; J Pediatr 141:572–575, 2002; Curr Prob in Derm 10:41–92, 1998; Medicine 62:195–208, 1983; Pediatrics 49:59–70, 1972; Lancet 1:1013–1015, 1966

Fetal hydantoin syndrome – hypertrichosis, broad depressed nasal bridge, large lips, wide mouth, short webbed neck, short stature, hypoplastic distal phalanges JAAD 46:161–183, 2002; hydantoin-­ barbiturate embryopathy – short, broad nose with anteverted nostrils, broad low nasal root, hypertelorism, low set dysplastic ears Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 450–451 Fetal valproic acid syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 452–453 Thalidomide embryopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 370–371

EXOGENOUS AGENTS Smoker’s face – linear wrinkling and atrophy AD 128:255–262, 1992 Fetal alcohol syndrome – short palpebral fissure, epicanthus, ptosis, short, flat nasal root, hypoplastic philtrum, thin upper lip, low set ears Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 480–483

INFECTIONS AND INFESTATIONS Leishmaniasis – personal observation Leprosy – leonine facies, loss of eyebrows and eyelashes (madarosis), saddle nose deformity, enlarged wrinkled earlobes Rubella embryofetopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 528–529 Syphilis, secondary with cranial nerve III palsy – personal observation

INFLAMMATORY DISORDERS Sarcoid – Heerfordt’s syndrome (uveoparotid fever) – massive facial swelling due to involvement of parotid glands NEJM 369:458, 2013; lacrimal gland enlargement, annular plaques, papules at margins of eyelids and ala nasi; lupus pernio, angiolupoid plaques, nasal septal perforation

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METABOLIC DISORDERS

PHOTODERMATOSES

Cushing’s syndrome – moon face, plethora, acne, androgenetic alopecia, hirsutism; bilateral macronodular adrenal hyperplasia NEJM 369:2115–2125, 2013; NEJM 369:2105–2114, 2013

Diffuse and macular atrophic dermatosis – generalized poikilodermatous prematurely aged (sun-damaged) appearance Clin Exp Dermatol 5:57–60, 1980

Diabetes mellitus – diabetic rubor Glycogen storage disease type 1 – Rubens or doll face Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 110–111

PRIMARY CUTANEOUS DISORDERS

GM1 gangliosidosis – coarse facies Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 132–133

Benign symmetric lipomatosis

Graves’ disease – exophthalmos, retracted or puffy eyelids, thyroid stare, thyrotoxicosis, neonatal – retraction of eyelids (thyroid stare), loss of subcutaneous fat NEJM 370:1237, 2014Homocystinuria – cystathionine beta-synthase deficiency; severe myopia; facies – midfacial hypoplasia, dental crowding, protruding maxilla, frontal bossing, downward lateral canthi, symmetric hypoplasia of midface and maxilla, relative mandibular hyperplasia; pectus excavatum and pectus carinatum, severe myopia NEJM 375:1879–1890, 2016; long Marfanoid facies Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 146–147 Hyperthyroidism – thinning eyebrows, alopecia, hyperhidrosis, anxious looking Hypothyroidism – dry dull looking skin, madarosis I-cell disease (mucolipidosis II) – puffy eyelids; small orbits, prominent eyes, fullness of lower cheeks; small telangiectasias; fish-mouth appearance, short neck; gingival hypertrophy Int J Paediatr Dent 13:41–45, 2003; Clin Genet 23:155–159, 1983; Birth Defects 5:174–185, 1969 Mannisodosis – large head, prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, prognathism Orphanet J Rare Dis July 23, 2008 Metabolic syndrome, including polycystic ovarian disease – personal observation Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, xerosis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; BJD 144:635–636, 2001; Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987

NEOPLASTIC DISORDERS Cutaneous T-cell lymphoma

Acanthosis nigricans – dirty brown velvety plaques of neck Cutis laxa Ped Derm 19:412–414, 2002; JAAD 29:846–848, 1993, Ped Derm 2:282–288, 1985  Inherited (dermatochalasis connata) – mutations in ELN1 (encoding elastin), FBLN5 (encoding fibulin-5), and FBLN4 (encoding fibulin-4)   Autosomal dominant – large earlobes, beaked nose JAAD 66:842–851, 2012; Clin Genet 39:321–329, 1991   Autosomal recessive – Types I (FBLN4), IIA (ATP6VOA2), IIB, III (PYCR1) Cutis laxa, craniofacial defects, and hypotonia J Clin Dysmorphol 1:24–25, 1983 Cutis laxa, autosomal recessive – ARCL2B – growth and developmental delay; triangular face Cutis laxa type IIIB – loose folds of wrinkled skin, progeroid facies, osteopenia, central nervous system abnormalities JAMADerm 155:257–259, 2019 Ehlers-Danlos type IV – deep set eyes with periorbital erythema; pinched nose Genetic Skin Disorders, Second Edition, 2010, pp. 387–389 Harlequin fetus (ichthyosis congenital fetalis) – autosomal recessive; rigid plates; severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis; ABCA 12 (adenosine triphosphate binding cassette A12); keratinocyte lipid transfer associated with lamellar granule formation and lipid transfer via lamellar granules on the surface of keratinocytes Harlequin fetus Ped Derm 26:575–578, 2009; BJD 158:611–613, 2008; BJD 155:204–206, 2006; AD 142:914–918, 2006; BJD 153:811–814, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982 Netherton’s syndrome – erythrodermic hyperkeratotic face with short crew cut hair; thick seborrheic like scale of scalp, eyebrows as well with trichrrhexis invaginata Oculocutaneous albinism Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 348–349 Progressive symmetric erythrokeratoderma – annular papulosquamous plaques of face Genetic Skin Disorders, Second Edition, 2010, pp50–52 Restrictive dermopathy – autosomal recessive, dysplastic low set ears; erythroderma at birth, with extensive erosions and contractures; taut shiny skin; fetal akinesia, multiple joint contractures, expressionless face with minimal creases; dysmorphic facies with fixed open mouth, hypertelorism, pulmonary hypoplasia, bone deformities; uniformly fatal AD 138:831–836, 2002; Ped Derm 19:67–72, 2002; Ped Derm 16:151–153, 1999; AD 134:577–579, 1998; AD 128:228–231, 1992;

PARANEOPLASTIC DISORDERS Acanthosis nigricans

SYNDROMES

Carcinoid syndrome

Aarskog syndrome (facio-digito-genital syndrome) – X-linked recessive – anteverted nostrils, long philtrum, broad nasal bridge; short broad hands with syndactyly, scrotal shawl (scrotal fold which surrounds the base of the penis); skeletal defects; learning disabilities Am J Med Genet 46:501–509, 1993; Am J Ophthalmol

Superior vena cava syndrome

Facies 109:450–456, 1990; Am J Med Genet 15:39–46, 1983; Hum Genet 42:129–135, 1978; J Pediatr 77:856–861, 1970 Aase-Smith syndrome (hypoplastic anemia with triphalangeal thumbs) – anti-mongoloid slant of palpebral fissures, cleft lip or palate, low nuchal hairline Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 436–437 Ablepharon macrostomia syndrome – absent eyelids, ectropion, abnormal ears, hypertelorism, aplasia or rudimentary nipples, dry, lax, redundant skin, macrostomia, ambiguous genitalia Hum Genet 97:532–536, 1996; Am J Med Genet 31:299–304, 1988 Achondrogenesis – macrocephaly, micromelia, hydrops Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 212–213 Acrocallosal syndrome (Greig cephalopolysyndactyly syndrome) – abnormal upper lids, frontonasal dysostosis, callosal agenesis, cleft lip/palate, redundant skin of neck, grooved chin, bifid thumbs, polydactyly, syndactyly Am J Med Genet 43:938–941, 1992 Acrodermatitis enteropathica – periorificial dermatitis, alopecia, glossitis, stomatitis Acrodysostosis type Maroteaux-Malamut) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 190–191 Acrofacial dysostosis (postaxial) (Genee-Wiedemann syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 418–419 Actinic prurigo BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981 Alagille syndrome (arteriohepatic dysplasia) – paucity of interlobular hepatic ducts; autosomal dominant; chronic cholestasis, xanthomas due to hypercholesterolemia, pruritus and failure to thrive; wispy hair, dysmorphic triangular face, broad forehead, deep-set eyes, upslanted palpebral fissures, mild hypertelorism, straight nasal bridge with saddle nose, small pointed chin, ventricular hypertrophy, peripheral pulmonary artery stenosis; atrial and ventricular septal defects, palmar linear plane xanthomas; supernumerary digital flexion creases of middle phalanges; vertebral, ocular and renal abnormalities; eyes – posterior embryotoxon (prominence of Schwalbe’s ring at junction of iris and cornea; Vitamins A, D, and E with follicular keratosis and hyperkeratosis of dorsal hands; JAG1 and Notch2 mutations Ped Derm 31:599–602, 2014; JAAD 58:S9–11, 2008; cutis laxa-like changes with resolution of xanthomas after liver transplantation Ped Derm 31:599–602, 2014; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, p. 553; Ped Derm 15:199–202, 1998   Follicular hyperkeratosis BJD 138:150–154, 1998   Porphyria cutanea tarda due to retained porphyrins Albright's hereditary osteodystrophy (pseudohypoparathyroidism) – osteoma cutis – periarticular calcified or ossified nodules (ectopic ossification); short stocky build; round face; low flat nasal bridge; short neck, brachymetaphalangism and brachydactyly; developmental delay, cataracts, hearing loss, seizures, poor dentition, basal ganglia calcification, osteomalacia, rickets, osteoporosis JAMA Derm 149:975–976, 2013; JAAD 15:353–356, 1986; AD 104:636– 642, 1971; Medicine 37:317–352, 1958 Ambras syndrome – hypertrichosis universalis congenital; fine silky light colored hair primarily of face, ears, shoulders, nose; associated minor facial dysmorphism, supernumerary nipples, dental anomalies Clin Genet 44:121–128, 1993 Amniotic band syndrome – asymmetric face, cleft lip, cleft palate Amyoplasia congenita disruptive sequence – mid-facial macular telangiectatic nevi Am J Med Genet 15:571–590, 1983 Angelman syndrome (happy puppet syndrome) – happy demeanor, excessive laughter, microcephaly with flat neck, fair skin and hair, widely spaced teeth and open mouth with protruding tongue

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Anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) J Dermatol 26:44–47, 1999; X-linked recessive – premature aged appearance with finely wrinkled skin, especially around eyes; absent or reduced sweating, hypotrichosis, and total or partial anodontia J Med Genet 28:181–185, 1991; autosomal recessive Ped Derm 7:242, 1990 Ankyloblepharon-ectodermal defects-clefting (AEC) syndrome – autosomal dominant; flat face, prominent nose, periorbital wrinkling, hypodontia, sparse hair, alopecia, sparse eyebrows and eyelashes; nail dystrophy; mutation in p63 BJD 166:134–144, 2012; Genetic Skin Disorders, Second Edition, 2010, pp. 271–276 Apert’s syndrome – autosomal dominant; FGFR-2 mutation; craniosynostosis with midfacial malformation; cone shaped calvarium, proptosis, hypertelorism, short nose with bulbous tip; high arched palate; lips bow-shaped, unable to form a seal; telangiectasias of face and bulbar conjunctiva, often in butterfly distribution; mottled hyperpigmentation, hypopigmentation and poikiloderma; seborrheic dermatitis, atopic dermatitis, and xerosis common Am J Med Genet 44:82–89, 1992; severe pustular acne at puberty Ped Derm 20:443–446, 2003 Ataxia telangiectasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 524–525 Atypical progeroid syndrome – autosomal recessive; diffuse mottled hyperpigmentation, foot ulcers, facial dysmorphism, recurrent infections, intellectual disability; prolidase deficiency; peptidase D deficiency Ped Derm 36:926–928, 2019 Baraitser syndrome (premature aging with short stature and pigmented nevi) – lack of facial subcutaneous fat, fine hair, hypospadius, dental abnormalities, hepatomegaly J Med Genet 25:53–56, 1988 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ablepharon, ectropion of lower eyelids, hypertelorism, long wide mouth (macrostomia), anteriorly folded ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Am J Med Genet 73:366–367, 1997; Am J Med Genet 47:20–23, 1993; Syndrome Ident 8:6–9, 1982 Bardet-Biedl syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 288–289 Bazex-Dupre-Christol syndrome (X-linked dominant) – milia and comedo-like papules, congenital hypotrichosis, anhidrosis, X-linked dominant, follicular (vermiculate) atrophoderma of the face, elbows and hands, hypohidrosis, basal cell nevi and basal cell carcinomas, trichoepitheliomas, pinched nose, keratosis pilaris, scrotal tongue, joint hypermobility; UBE 2A gene Ped Derm 28:727–728, 2011; Ped Derm 25:112–113, 2008; Ped Derm 23:149–151, 2006; BJD 153:682–684, 2005; Dermatol Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; JAAD 39:853–857, 1998; J Med Genet 33:493–497, 1996; AD 130:337–342, 1994; Hautarzt 44:385–391, 1993; J Cutan Pathol 18:20–27, 1991; Clin Exp dermtol 6:31–41, 1981; Ann Dermatol Syphilgr (Paris) 93:241–254, 1966; Bull Soc Franc Derm Syph 71:206, 1964 Beare-Stevenson syndrome – acanthosis nigricans, hypertelorism, cleft palate, bifid scrotum, large umbilical stump, skin furrows of the face, hands, feet, axilla, and/or perineum, cutis verticis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital anomalies, early death Ped Derm 20:358–360, 2003; Am J Med Genet 44:82–89, 1992; BJD 81:241, 1969

408 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Beckwith-Wiedemann syndrome (exomphalos-macroglossia-gigantism syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 136–137 Berardinelli-Seip syndrome – facial lipoatrophy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 280–281 Bird-headed Seckel-like type with osteodysplasia (primordial microcephalic and osteoplastic dwarfism) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 170–171 Blepharophimosis syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 156–157 Blepharophimosis, camptodactyly, small stature, mental retardation, sensorineural hearing loss Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 160–161 Blepharomosis, pterygium colli, flexion contractures of fingers and toes, osteodysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 510–511 Bloom's syndrome (congenital telangiectatic erythema and stunted growth) – autosomal recessive; long facies; blisters of nose and cheeks; slender face, prominent nose with sculptured nasal tip; large ears, small jaw, facial telangiectatic erythema with involvement of eyelids, ear, hand and forearms; bulbar conjunctival telangiectasias; stunted growth; CALMs, clinodactyly, syndactyly, congenital heart disease, annular pancreas, high-pitched voice, testicular atrophy; no neurologic deficits; type II diabetes mellitus, decreased Igm and IgA with sinopulmonary infections including pneumonia; internal malignancy JAAD 75:855–870, 2016; Ped Derm 22:147– 150, 2005; Curr Prob Derm 14:41–70, 2002; Ped Derm 14:120–124, 1997; JAAD 17:479–488, 1987; AD 114:755–760, 1978; Clin Genet 12:85–96, 1977; Am J Hum Genet 21:196–227, 1969; Am J Dis Child 116:409–413, 1968; AD 94:687–694, 1966; Am J Dis Child 88:754–758, 1954 Brachymetapody syndrome (Tuomaala-Haapanen syndrome) – albinoid skin – short stature, shortening of all digits but thumbs, hypoplastic maxilla, anodontia, hypotrichosis, hypoplastic breasts and genitalia, strabismus, distichiasis Syndromes of the Head and Neck, p. 834, 1990; Acta Ophthalmol 46:365–371, 1968 Braegger syndrome – proportionate short stature, IUGR, ischiadic hypoplasia, renal dysfunction, craniofacial anomalies, postaxial polydactyly, hypospadias, microcephaly, mental retardation Am J Med Genet 66:378–398, 1996 Branchiooculofacial syndrome – autosomal dominant; congenital bilateral cervical ulcerations (bilateral ectopic thymus glands); congenital ulcerated neck mass (ectopic thymus), flattened nasal tip, pseudo-­cleft lip, posterior rotated ears, pre-auricular pit, cleft lip, microphthalmia, coloboma, nasolacrimal duct stenosis or atresia, dolichocephaly; mutation in TFAP2A (retinoic acid responsive gene) Ped Derm 29:759–761, 2012; Mol Vis 16:813–818, 2010; Arch Otolaryngol Head Neck Surg 128:714–717, 2002 (pseudocleft of upper lip, cleft-lip-­palate, and hemangiomatous branchial cleft) – atrophic neck lesions Ped Derm 29:383–384, 2012; Am J Med Genet 27:943–951, 1987 Camptomelic dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 232–233 Capillary malformations, branchial clefts, lip pseudoclefts, and unusual facies; anomalous retroverted ears, microphthalmia, cleft lip/palate JAAD 56:541–564, 2007; J Laryngol Otol 71:597–603, 1957 Cardio-facio-cutaneous syndrome – autosomal dominant, xerosis/ ichthyosis, eczematous dermatitis, alopecia, growth failure, hyperkeratotic papules, ulerythema ophryogenes (decreased or absent eyebrows), seborrheic dermatitis, CALMs, nevi, hemangiomas, keratosis pilaris, patchy or widespread ichthyosiform eruption,

sparse curly scalp hair and sparse eyebrows and lashes, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies with macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of supraorbital ridges, short nose with depressed nasal bridge, high arched palate, low set posteriorly rotated ears with prominent helices, cardiac defects including pulmonic stenosis, atrial septal defect, hypertrophic cardiomyopathy; RASopathy with gain of function sporadic missense mutations in BRAF, KRAS, MEK1, or MEK2, MAP2K1/MAP2K2 BJD 163:881– 884, 2010; Ped Derm 27:274–278, 2010; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992 Carpenter syndrome (acrocephalopolysyndactyly type Carpenter) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 22–23 Cartilage-hair hypoplasia (metaphyseal chondrodysplasia of McKusick) (disproportionate short stature; short limb skeletal dysplasia) – autosomal recessive; short limb dwarfism, mild leg bowing with short limbs, short sparse, lightly colored hair; soft doughy skin, small dystrophic fingernails; some with total baldness, immune defects; mutation in mitochondrial RNA processing; endoribonuclease; 9p13 JAAD 54:S8–10, 2006; Am J Med Genet 66:378–398, 1996; Eur J Pediatr 155:286–290, 1996; Eur J Pediatr 142:211–217, 1993; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 264–265; Am J Med Genet 41:371–380, 1991; Bull Johns Hopkins Hosp 116:285–326, 1965 Catel-Schwartz-Jampel syndrome (chondrodysplasia myotonia) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 508–509 Cat-eye syndrome (coloboma-anal atresia syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 66–67 CEDNIK syndrome (cerebral dysgenesis-neuropathy-ichthyosis-­ keratoderma) – microcephaly; dysmorphic face with small anterior fontanelles; pointed prominent nasal tip, small chin, inverted nipples and long toes, high palate, thick gingivae, cradle cap, sparse brittle coarse hair, scarring alopecia, fixed flexion posture; decreased SNAP 29 protein; mutation in SNARE proteins mediating vesicle trafficking; mutation in ABCA12 gene BJD 164:610–616, 2011; AD 144:334–340, 2008 Cerebro-oculo-facial-skeletal syndrome (in aboriginal families) – microcephaly, facies – micrognathia, small eyes, enlarged ears, bulbous nose, prominent nasal bridge, microphthalmia with poor vision, cataracts, blepharophimosis, short palpebral fissures, onychogryphosis, photosensitivity, mental retardation, hyperkinesis, failure to thrive, developmental delay, hypotonia, orthopedic anomalies (kyphoscoliosis), joint contractures; overhanging upper lip, small jaw JAAD 75:873–882, 2016; Ped Derm 26:97–99, 2009; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, p. 556; JAMA Derm 149:1414–1418, 2013 Cerebro-costo-mandibular syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 72–73 Chanarin-Dorfman disease – coarse facies, ichthyosis with fine scaling of trunk, renal disease BJD 176:545–548, 2017 Cherubism – autosomal recessive; bony enlargement of mandible and maxilla; hypertrichosis of face and pubic region CHOPS syndrome – coarse facies, heart defects, obesity, pulmonary involvement, short stature, long eyelashes, synophrys Am J Med Genet 179:1126–1138, 2019 Chronic granulomatous disease – facial seborrheic dermatitis like eruption; recurrent suppurative skin infection – furuncles; cervical/ inguinal lymphadenitis and draining abscesses over involved nodes; pustular/vesicular dermatitis often periorificial and scalp; 30% female carriers with DLE

Facies Chondrodysplasia punctata, autosomal recessive – flat face with full cheeks, broad depressed nasal root Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 220–221 Chondrodysplasia punctata, X-linked dominant Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 226–227 Classic arthrogryposis:amyoplasia – round face with capillary malformation Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 402–403 Cleidocranial dysplasia (Scheuthauer-Marie syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 32–33 Cloverleaf skull – Kleeblattschadel deformity; craniosynostosis; trilobed skull, exophthalmos, low ear implantation, hydrocephalus common Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 24–25 Cockayne syndrome – xerosis with rough, dry skin, anhidrosis, erythema of hands, hypogonadism; autosomal recessive; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects including retinal degeneration, demyelination JAMA Derm 149:1414–1418, 2013; Ped Derm 20:538–540, 2003; Am J Hum Genet 50:677–689, 1992; J Med Genet 18:288–293, 1981; birdheaded dwarfism Cohen syndrome – microcephaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 290–291 Coffin-Lowry syndrome – X-linked inheritance; straight coarse hair, prominent forehead, prominent supraorbital ridges, hypertelorism, large nose with broad base, thick lips with mouth held open, large hands, tapering fingers, severe mental retardation; loose skin easily stretched, cutis marmorata, dependent acrocyanosis, varicose veins Clin Genet 34:230–245, 1988; Am J Dis Child 112:205–213, 1966; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 28–29 Coffin-Siris syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 174–175 COH syndrome – cloverleaf skull, polymicrogyria, absent olfactory tracts and bulbs, proptosis, low nasal bridge, short upturned nose, downturned mouth, narrow palate, thumb duplication, small fifth fingers, micropenis, bifid scrotum, agenesis of cervical thymic lobes, bilobed lungs Syndromes of the Head and Neck, 3rd Edition, pp. 546–547, 1990 Collodion baby – translucent membrane of face Genetic Skin Disorders, Second Edition, 2010, pp. 25–28 Congenital circumferential skin folds – mountain range appearance; dysmorphic features, ear abnormalities, prominent philtrum with central ridge Ped Derm 29:89–95, 2012 Congenital disorders of glycosylation (CDG-Ia) – phosphomannomutase-­2; redundant excess fat; peau d’orange skin; facial dysmorphism, cerebellar hypoplasia, hypotonic neonate, strabismus Ped Derm 22:457–460, 2005 Congenital disorders of glycosylation (CDG-Ix) – nuchal skin folds, facial dysmorphism, inverted nipples, hypoplastic nails, petechiae and ecchymoses, edema; neurologic, gastrointestinal and genitourinary abnormalities, pericardial effusion, ascites, oligohydramnios Ped Derm 22:457–460, 2005 Congenital ichythyosis, hypogonadism, small stature, facial dysmorphism, scoliosis, and myogenic dystrophy Ann Genet 42:45–50, 1999 Conidiobolus coronatus infection – personal observation

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Conradi-Hunermann-Happle disease (chondrodysplasia punctata) – frontal bossing, low nasal bridge, pinced nostrils, full lips and philtrum, orbital arch hypoplasia, atrophoderma vermiculata, chondrodysplasia punctate, asymmetric shortening of limbs, stippled epiphyses, congenital erythroderma; patchy scarring alopecia, thinning to absent eyelashes and eyebrows, Blaschko ichthyosiform eruption BJD 166:830–838, 2012; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 222–223 Contractural arachnodactyly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 144–145 Cornelia de Lange (Brachmann-de Lange) syndrome – hypoplastic epidermal ridges of palms, soles, fingers, and toes; single palmar crease, hypoplastic nipples and umbilicus, umbilical hernia Syndromes of the Head and Neck, p. 303, 1990; generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, posterior neck, and arms, low set ears, arched palate, antimongoloid palpebrae; congenital eyelashes; xerosis, especially over hands and feet, nevi, facial cyanosis, lymphedema Ped Derm 24:421–423, 2007; JAAD 56:541–564, 2007; JAAD 48:161–179, 2003; JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993 Costello syndrome – warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977; coarse face with furrowed forehead and scalp, broad nose, wide anteverted nares, thick lips, dysplastic ears Ped Derm 30:665–673, 2013 Cowden’s syndrome – keratoses of face and extremities; trichilemmomas around eyes, mouth, nasolabial folds, and pre-auricular areas; oral papillomas (cobblestoning); acrochordons of face, neck, axillae; scrotal tongue, oral fibromas and lipomas; macrocephaly, midfacial hypoplasia Craniocarpotarsal dysplasia (whistling face syndrome) – ptosis J Med Genet 14:139–141, 1977 Craniodysostosis with extremity bands – personal observation Craniometaphyseal dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 104–105 Craniosynostosis, anal anomalies, and porokeratosis (CAP/ CDAGS) – autosomal recessive; craniosynostosis, clavicular hypoplasia, delayed fontanel closure, cranial defects (parietal foramina), deafness, imperforate anus or anterior placement of anus, genitourinary abnormalities (hypospadias and urethrorectal fistula), and skin eruption (porokeratosis-­like lesions), mental retardation, scant hair, Staphylococcus aureus infections JAAD 68:881–884, 2013; Am J Hum Genet 77:161–168, 2005; J Med Genet 35:763–766, 1998 Cri Du Chat syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 92–93 Crouzon syndrome with acanthosis nigricans (CAN) – onset of acanthosis nigricans during childhood, melanocytic nevi, craniosyn-

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ostosis, ocular proptosis, midface hypoplasia with parrot-beak nose, choanal atresia, hypertelorism, anti-Mongoloid slant, posteriorly placed ears, hydrocephalus; mutation in FGFR3 JAMA Derm 149:737–741, 2013; Ped Derm 27:43–47, 2010; Am J Med Genet 84:74, 1999

Down’s syndrome (trisomy 21) – short stature, cutis marmorata, acrocyanosis, low-set, small ears; upslanted palpebral fissures, flat nasal bridge, nuchal folds, single palmar flexion crease, clinodactyly of fifth finger, hypotonia NEJM 382:2344–2352, 2020; JAAD 46:161–183, 2002

Cryptophthalmos syndrome (Fraser syndrome) – malformed ears Am J Med Genet 31:159–168, 1988

Dubowitz syndrome – autosomal recessive, microcephaly, sloping forehead, telecanthus, erythema and scaling of face and extremities in infancy, sparse blond scalp and arched eyebrow hair, dysplastic low set ear pinnae, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities; syndactyly, cryptorchidism, hypospadius, developmental delay, transitory short stature, hyperactive behavior, blepharophimosis, ptosis of the eyelids, epicanthal folds, broad nose, palate anomalies, micrognathia, and severe atopic dermatitis Ped Derm 22:480–481, 2005; Am J Med Genet 63:277–289, 1996; Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959–964, 1993; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 176–177; Eur J Pediatr 144:574–578, 1986; Am J Med Genet 4:345–347, 1979; J Med Genet 2:12–17, 1965

Curry-Jones syndrome – linear hypo- or hyperpigmented lesions, palmoplantar pitting, streaks of atrophy, hypertrichosis, trichoblastomas and nevus sebaceous, polydactyly or preaxial polysyndactyly, dysmorphic facies, macrocephaly, microcephaly, dental anomalies, craniosynostosis, anal stenosis, myofibromas and smooth muscle hamartomas, medulloblastomas, cerebral malformations (agenesis of corpus callosum), developmental delay, cataracts, microphthalmia, coloboma, glaucoma, cryptorchidism; mutation in SMOc.1234C>T BJD 182:212–217, 2020; Clin Dysmorphol 4:116–129, 1995 Cutis tricolor parvimaculata (twin spotting – didymosis) – small café au lait macules and hypopigmented macules; ring chromosome 15 syndrome; low birth weight, failure to thrive, microcephaly, triangular face, clinodactyly, mental retardation Ped Derm 28:670–673, 2011; Dermatology 211:149–151, 2005 Daughter of CYLD mutation – dysmorphic facies with anteverted nares, long philtrum, retroverted small ears, retrognathia, mild intellectual disability, renal hypoplasia JAAD 81:1300–1307, 2019 Darier’s disease – personal observation DeBarsy syndrome – aged appearance of infants with thin skin of face and pinched midface with lack of subcutaneous tissue and wrinkled appearance of skin elsewhere; large appearing deep set eyes, frontal bossing, hypertelorism, abnormal posteriorly large rotated ears, pinched or beaked nose Genetic Skin Disorders, Second Edition, 2010, pp. 644–645; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 276–277 Delleman syndrome – autosomal dominant with variable penetrance, multiple craniofacial skin tags, striated muscle hamartomas, orbital cysts (exophthalmia or microthalmia), cerebral malformations, periorbital or postauricular appendages, focal dermal hypoplasia and aplasia (aplasia cutis congenita), rib defects, psychomotor retardation, seizures, skull defects; no ear abnormalities Clin Genet 19:191–198, 1981 Diastrophic dyplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 236–237 Depigmented hypertrichosis with dilated follicular pores, short stature, scoliosis, short broad feet, macrocephaly, dysmorphic facies, supernumery nipple, and mental retardation (cerebral-ocular malformations) BJD 142:1204–1207, 2000 DeSanctis-Cacchione syndrome (variant of XP with neurologic manifestations) Hum Mol Genet 9:1171–1175, 2000; Indian J Pediatr 64:269–272, 1997; AD 115:676, 1979; Neurol Psychiatr (Bucur) 16:47–51, 1978; AD 113:1561–1563, 1977; JID 63:392– 396, 1974 Digitocutaneous dysplasia – X-linked dominant; digital fibromas, atrophic plaques with appearance of hyperpigmentation, metacarpal and metatarsal disorganization with resultant brachydactyly and clinodactyly, dysmorphic features including frontal bossing, broad nasal root, telecanthus and epicanthal folds, conical teeth, dental fissures, hypodontia, accessory gingival frenula, enamel hypoplasia JAAD 56:S6–9, 2007 Donahue syndrome (leprechaunism) – congenital insulin resistance; dwarfism; elfin-like face, large eyes, thick lips, low set ears, less subcutaneous fat, excessive folding of skin Pediatr 83:18, 1994; AD 117: 531–535, 1981

Dwarfism, bilateral club feet, premature aging, progressive panhypogammaglobulinemia J Rheumatol 21:961–963, 1994 Dyskeratosis congenita – reticulated hyperpigmentation of neck, upper chest, arms; telangiectatic component, oral leukoplakia; involvement of lacrimal puncta can lead to chronic blepharitis and excessive tearing Ectodermal dysplasia – preauricular pits, tetra-amelia, ectodermal dysplasia, hypoplastic lacrimal ducts and sacs opening toward exterior, peculiar facies, developmental retardation Ann Genet 30:101–104, 1987 Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC syndrome) – perioral and labial vegetative papillomatous plaques; perleche; high forehead, maxillary hypoplasia, mandibular protrusion Ped Derm 27:658–660, 2010; J Eur Acad DV 17:356–358, 2003; Ped Derm 19:330–332, 2002; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 386–387 Ehlers-Danlos syndrome – unusual appearance of ears; EDS type IV (acrogeria de Gottron)– lobeless ears; acrogeric skin type; prominent eyes; dry wrinkled (not hyperelastic) pigmented skin of arms and legs; pinched nose; thin translucent skin with prominent vascular pattern and bruising; joint hyperextensibility; abnormal type III collagen and defect in type III collagen synthesis; spontaneous vascular or bowel rupture; BJD 163:704–710, 2010;JAAD 55:S41– 45, 2006; (acrogeria (Gottron’s syndrome) – micrognathia, atrophy of tip of nose, atrophic skin of distal extremities with telangiectasia, easy bruising, mottled pigmentation or poikiloderma of extremities, dystrophic nails BJD 103:213–223, 1980) Ehlers-Danlos syndrome type IV (acrogeric type) – acrogeric appearance (thinning and translucency of skin) BJD 144:1086– 1087, 2001; Rook, p. 2035, 1998, Sixth Edition; type VIII – autosomal dominant; skin fragility, abnormal scarring, severe early periodontitis with loss of adult dentition by end of third decade; cigarette paper scars of shin; marfanoid habitus (tall, long limbs, arachnodactyly); triangular face, prominent eyes, thin nose, prematurely aged appearance, thin skin with prominent veins, no joint hypermobility, easy bruising, blue sclerae JAAD 55:S41–45, 2006 Ehlers-Danlos syndrome type VII (dermatoparaxis) – doughy appearance of facial skin, skin sags around eyes with puffiness; easy bruising, micrognathia, blue-gray sclerae, gingival hypertrophy Elejalde syndrome (neuroectodermal (neurocutaneous) melanolysosomal disease) – silvery hair, bronze colored skin; profound central nervous system dysfunction; hypotonic facies, plagiocephaly,

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micrognathia, crowded teeth, narrow high palate, pectus excavatum, cryptorchidism; normal immune system; defective transfer of melanosomes JAAD 55:337–340, 2006; AD 135:182–186, 1999; JAAD 38:295–300, 1998

Fibrochondrogenesis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 242–243

Ellis-van Creveld syndrome (chondroplastic dwarf with defective teeth and nails, and polydactyly) (chondroectodermal dysplasia) – autosomal recessive; very short stature; chondrodysplasia, ectodermal dysplasia with ulnar polydactyly, cone- and peg-shaped teeth or hypodontia, enamel hypoplasia, fused incisors, molars with extra cusps, dental fissures and pits, neonatal teeth, malocclusion; short upper lip bound down by multiple labiogingival frenulae; gingival hypertrophy, nail dystrophy, hair may be normal or sparse and brittle; cardiac defects; ichthyosis, palmoplantar keratoderma; asymmetric distal limb shortening; short distal phalanges with small dystrophic fingernails; congenital heart disease; hypospadias, cryptorchidism; mutations in EVC and EVC2 Cutis 83;303–305, 2009; Ped Derm 18:485–489, 2001; J Med Genet 17:349–356, 1980; Arch Dis Child 15:65–84, 1940; short upper lip Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 244–245

Floating-Harbor syndrome (unusual facies, short stature, hypoplastic penis) – autosomal dominant; mutation SRCAP; triangular face, low set ears, low hairline, deep set eyes, trichomegaly, long triangular shaped nose, low hanging coluella, short philtrum, thin lips; hypoplastic penis Balkan J Med Genet 21:83–86, 2018; Birth Defects 11:305–309, 1975

Encephalocraniocutaneous lipomatosis – lipomatous hamartomas of sclerae and intracranial Fabry’s disease – recessed forehead, bushy eyebrows, prominent supraorbital ridges, wide nasal bridge, bulbous nasal tip, full lips, coarse features, posteriorly rotated ears, prognathism; angiokeratomas rarely on hands, feet, or face BJD 166:712–720, 2012S FACES (unique facies, anorexia, cachexia, eye, skin lesions) J Craniofac Genet Dev Biol 4:227–231, 1984 Familial lipoatrophic diabetes Genetic Skin Disorders, Second Edition, 2010, pp. 511–513 Familial mandibuloacral dysplasia (craniomandibular dermatodysostosis) – onset at age 3–5 years; atrophy of skin over hands and feet with club shaped terminal phalanges and acro-osteolysis, mandibular dysplasia, delayed cranial suture closure, short stature, dysplastic clavicles, prominent eyes and sharp nose, alopecia, sharp nose, loss of lower teeth, multiple Wormian bones, acroosteolysis Ped Derm 22:75–78, 2005; BJD 105:719–723, 1981; Birth Defects x:99–105, 1974 Fanconi’s anemia – autosomal recessive; endocrine abnormalities with hypothyroidism, decreased growth hormone, diabetes mellitus, café au lait macules, diffuse hyperpigmented macules, guttate hypopigmented macules, intertriginous hyperpigmentation, skeletal anomalies (thumb hypoplasia, absent thumbs, radii, carpal bones), oral/genital erythroplasia with development of squamous cell carcinoma, hepatic tumors, microphthalmia, ectopic or horseshoe kidney, broad nose, epicanthal folds, micrognathia, bone marrow failure, acute myelogenous leukemia, solid organ malignancies (brain tumors, Wilms’ tumor) BJD 164:245–256, 2011; JAAD 54:1056–1059, 2006; Ped Derm 16:77–83, 1999 Fanconi syndrome, ichthyosis, dysmorphism, jaundice, and diarrhea Pediatr Nephrol 4:308–313, 1990 Farber's disease (lipogranulomatosis) – skin colored nodules overlying joints, larynx, and scalp; deformed or stiff joints and periarticular subcutaneous nodules; coarse facial features Ped Derm 21:154–159, 2004; Eur J Ped 157:515–516, 1998; AD 130:1350–1354, 1994 Femoral hypoplasia-unusual facies syndrome – hypoplastic penis J Med Genet 21:331–340, 1984 FG syndrome (Opitz-Kareggia syndrome) – unusual facies, mental retardation, congenital hypotonia, imperforate anus; small ears; broad flat thumbs, macrocephaly, tall forehead, upswept frontal hairline, hypertelorism Am J Med Genet A 161A:2734–2740, 2013; Am J Med Genet 12:147–154, 1982

Filippi syndrome – short stature, microcephaly, characteristic face, syndactyly, mental retardation Genet Couns 4:147–151, 1993

Fragile X syndrome – long narrow face, large ears, flexible fingers, large testicles, soft skin, hypotonia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 100–101 Fraser syndrome (cryptophthalmos-syndactyly syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 74–75 Frontonasal dysplasia (median cleft face syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 40–41 GAPO syndrome (growth retardation, alopecia of scalp, eyelashes, and body hair, pseudoanodontia, optic atrophy) – doughy appearance of face with coarse wrinkling, full lips, cherubic appearance of jaws, frontal bossing, midfacial hypoplasia Gaucher’s disease Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 114–115 Geroderma osteodysplastica (Bamatter syndrome) (osteodysplastic geroderma) – autosomal recessive; short stature, cutis laxa-like changes with drooping eyelids and jowls (characteristic facies with hypoplastic midface), alopecia, bone fragility with osteoporosis and skeletal abnormalities, scoliosis; lax wrinkled, atrophic skin, joint hyperextensibility, growth retardation; macrocephaly, Ped Derm 23:467–472, 2006; Ped Derm 16:113–117, 1999; Am J Med Genet 3:389–395, 1979; Hum Genet 40:311–324, 1978; Ann Paediatr 174:126–127, 1950 Gingival fibromatosis with distinctive facies – autosomal recessive; macrocephaly, hypertelorism, bushy eyebrows, synophrys, downslanted palpebral fissures, flat nasal bridge with hypoplastic nares, cupid-bow mouth, high arched palate Ped Derm 18:534–536, 2001 Gingival fibromatosis-hypertrichosis syndrome – – autosomal dominant; excessive body and facial hair; gingival hyperplasia which engulf the teeth; gums pink, extremely firm, pebbly or nodular Goldenhaar syndrome (oculo-auriculo-vertebral syndrome) (hemifacial microsomia) – facial hemiatrophy; accessory tragi (preauricular tags); ocular lipodermoids, epibulbar dermoids; multiple vertebral anomalies, gastrointestinal anomalies, microphthalmia, anophthalmia, colobomata, genital anomalies, micrognathia, microtia, cleft lip/ palate, hemifacial microsomia, urologic anomalies, cardiac anomalies, pulmonary anomalies Ped Derm 24:657–658, 2007; JAAD 50:S11–13, 2004; Syndromes of the Head and Neck, pp. 641–649, 1990; aplasia cutis congenita JAAD 50:S11–13, 2004 Goltz’s syndrome (focal dermal hypoplasia) Harlequin fetus – thick plate-like scales with ectropion, eclabium, crumpled ears, fixed oval mouth; patchy alopecia, brittle hair, sparse; eye abnormalities (strabismus, colobomas, photophobia, microphthalmia); oligodontia, dysplastic teeth, enamel defects; fleshy or vascular oral or nasal papillomas Gorlin-Chaudhry-Moss syndrome – short and stocky with craniosynostosis, midface hypoplasia, hypertrichosis of the scalp, arms, legs, and back, anomalies of the eyes, digits, teeth, and heart, and genitalia hypoplasia Am J Med Genet 44:518–522, 1992 Greig’s polysyndactyly-cranial dysmorphism syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 414–415

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Hajdu-Cheney syndrome – autosomal dominant; NOTCH2 mutation; acroosteolysis, osteoporosis, joint hypermobility, short stature, polycystic kidneys; broad heavy eyebrows, maxillary and mandibular hypoplasia, broad philtrum, broad thin lipped mouth, coarse, thick scalp hair; micrognathia, synophrys, hypertelorism, coarse facial features Curr Osteoporos Rep 14:126–131, 2016; Orphanet J Rare Dis Dec 10, 2014 Hallermann-Streiff syndrome (oculomandibulofacial syndrome) – premature aging; facial skin atrophic, thin and taut appearing; telangiectasias common; dyscephaly – abnormal shape of head and face with small cranium; “bird-headed dwarfism” round face, sparse hair, beaked nose, micrognathia, small palpebral fissures, small mouth, broad forehead; pinched beak nose, everted lower lip, extraordinary retrognathia, parrot-like appearance, frontal and/or occipital bossing, atrophy of skin especially of nose, proportionate dwarfism, microphthalmos, cataracts, sparse eyebrows and eyelashes Clin Exp Dermatol 29:477–479, 2004 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia, coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hemimaxillofacial dysplasia (segmental odontomaxillary dysplasia) (HATS – hemimaxillary enlargement, asymmetry of face, skin findings)– facial asymmetry, hypertrichosis of the face, unilateral maxillary enlargement, partial anodontia, delayed eruption of teeth, gingival thickening of affected segment, Becker’s nevus, hairy nevus (hypertrichosis), lip hypopigmentation, depression of cheek, erythema, hypoplastic teeth Ped Derm 21:448–451, 2004; JAAD 48:161–179, 2003; Oral Surg Oral Med Oral Pathol 64:445–448, 1987 Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, hirsutism, bilateral single palmar crease, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006 Hereditary carpotarsal osteolysis with nephropathy – proteinuria; mild exophthalmos, hypoplasia of upper jaw, micrognathia; triangular face, corneal opacity; MAFB mutation BMC Med Genet 19:164, 2018 Hoyeraal-Hreidarsson syndrome – reticulate hyperpigmentation (resembles dyskeratosis congenita), alopecia, growth retardation, intrauterine growth retardation, microcephaly, mental retardation, hypoplasia of the cerebellum, vermis, and corpus callosum, and cerebral white matter demyelinization, progressive bone marrow failure, and mucocutaneous lesions SKINmed 12:117–118, 2014; J Pediatr 136:390–393, 2000 Hughes syndrome – autosomal dominant; acromegaloid features and thickened oral mucosa; thickened fissured lips; distinct from pachydermoperostosis, MEN IIb, III, and Ascher syndrome J Med Genet 22:119–125, 1985

Hunter’s syndrome (mucopolysaccharidosis type II) – fleshy ivory white papules and nodules (pebbling) in ridging or reticular pattern, symmetric, involving area between the angle of the scapula and anterior axillary line; coarse facial features, luxuriant scalp hair; bony abnormalities, recurrent umbilical and inguinal hernias; recurrent otitis media and pneumonia; developmental delay; coarse straight scalp hair; hypertrichosis of body and face; slate grey nevi; bilateral knee pain; decreased sulfoiduronate sulfatase (L-iduronate2-sulfatase) resulting in buildup of dermatan sulfate and heparin sulfate Ped Derm 37:369–370, 2020; Ped Derm 15:370–373, 1998 Hurler’s syndrome (mucopolysacchariosis type I-H) Hutchinson-Gilford progeria syndrome – mountain range rippling of skin; sclerodermoid changes of trunk and thighs; facies – midface hypoplasia, prominent scalp veins, circumoral cyanosis, absent earlobes, mid-frontal bossing, beaklike nose, protruding ears with small lobes, prominent eyes, glyphic nose (broad, mildly concave nasal ridge), mild micrognathia, vertical midline groove of chin, thin lips, osteoporosis, alopecia, arthritis, loss of subcutaneous fat, nail hypoplasia, bruising, irregular hyperpigmentation, delayed dentition, high pitched voice; mutation in LMNA JAMADerm 150:197–198, 2014; BJD 156:1308–1314, 2007 Hurst syndrome – short stature, hypertonia, unusual facies, mental retardation, hemolytic anemia, delayed puberty Am J Med Genet 29:107–115, 1988; Am J Med Genet 28:965–970, 1987 Hutchinson-Gilford syndrome (progeria) – age of onset is 1–2 years, short stature, weight low for height, loss of subcutaneous fat, plucked bird appearance, bluish tinge around mouth and nasolabial folds (mid-facial cyanosis); lax and wrinkled skin, prominent scalp veins, hyper- and hypomelanosis in sun-exposed areas, alopecia, mid-facial cyanosis around mouth and nasolabial folds, decreased sweating, sclerodermoid changes, cobblestoning of soft pebbly nodules, acro-osteolysis, widened metaphyses, and osteoporosis Ped Derm 22:75–78, 2005; Am J Med Genet 82:242–248, 1999; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 270–271 Hypertelorism-microtia-clefting syndrome (Bixler syndrome) J Med Genet 19:387–388, 1982 Hypertrichosis, coarse face, brachydactyly, obesity, mental retardation, broad proximal phalanges, small dysmorphic nails Clin Dysmorphol 5:223–229, 1996 Hypertrichosis, pigmentary retinopathy, and facial anomalies – lipoatrophy of buttocks Am J Med Genet 62:386–390, 1996 Hypohidrotic ectodermal dysplasia – periorbital hyperpigmentation with fine wrinkling, saddle nose deformity Genetic Skin Disorders, Second Edition, 2010, pp. 286–291; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 456–457 Hypophosphatasia – craniosynostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 252–253 Hypotrichosis-Lymphedema-Telangiectasia-Renal failure syndrome – diffuse reticulated capillary malformation, hypertensive emergency with transient ischemic attack, dilatation or aortic root, pleural effusions, acute kidney injury, thin facies with telangiectasias of cheeks, livedo reticularis of trunk and extremities; mutation in SOX18 gene Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016 Immuno-osseous dysplasia – short-limbed dwarfism, immunodeficiency, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation) Ped Derm 23:373–377, 2006 Incomplete triploidy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 150–151

Facies Jackson-Weiss syndrome – mutation in FGFR2; craniosynostosis, midfacial hypoplasia, foot anomalies in large Amish kindred J Pediatr 88:963–968, 1976 Joint dysplasia-short stature-erythema telangiectasia – telangiectatic erythema of face Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 258–259 Julia Pastrana syndrome – congenital generalized hypertrichosis terminali – facial deformities and gingival hyperplasia Am J Med Genet 47:198–212, 1993 Juvenile hyaline fibromatosis (Murray-Puretic syndrome) – autosomal recessive; translucent pearly white papules or nodules of scalp, face (chin, nasolabial folds, forehead, ears, back of, neck, perianal nodules), trunk, gingival hypertrophy, larger papules and nodules around nose, behind ears, on fingertips, multiple subcutaneous nodules of scalp, trunk, and extremities, flexion contractures of large and small joints papillomatous perianal papules; joint contractures, skeletal lesions, gingival hyperplasia, stunted growth, sclerodermiform atrophy; infiltration of small and large intestine; CMG2 (capillary morphogenesis gene 2) gene JAAD 61:695–700, 2009; JAAD 58:303–307, 2008; Eur J Pediatr 168:363–365, 2008; Ped Derm 21:154–159, 2004; Arch Ped 4:1200–1204, 1997; JAAD 16:881–883, 1987; perinasal and fold of chin Ped Derm 6:68–75, 1989 Kabuki makeup syndrome – pre-auricular dimple/fistula, short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170– 173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849– 850, 1984; J Pediatr 99:565–569, 570–573, 1981 KBG syndrome – autosomal dominant; macrodontia, characteristic facial features with triangular face, bushy eyebrows, bulbous nose, synophrys Orphanet Rare Dis Dec 19, 2017 Kearns-Sayre syndrome (mitochondrial encephalomyopathy) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 500–501 Keutel syndrome – rare autosomal recessive; abnormal diffuse cartilage calcification, hypoplasia of midface, hearing loss, peripheral pulmonary stenosis; short distal phalanges resembling a drum stick Keratosis-ichthosis-deafness syndrome – verrucous ichthyosiform scaling of entire face with hyperkeratosis of angles of mouth and vermilion and vermilion border of lips, cheesy appearance of scalp Genetic Skin Disorders, Second Edition, 2010, pp. 126–130 Kindler's syndrome – acral blistering at birth; progressive poikiloderma; cigarette paper atrophy of hands and feet (scleroatrophy), atrophied gingiva, photosensitivity; mutation in FERMT1 (fermitin family homologue 1) gene BJD 160:233–242, 2009; BJD 159:1192– 1196, 2008; BJD 158:1375–1377, 2008; BJD 157:1252–1256, 2007; BJD 157:1281–1284, 2007; AD 142:1619–1624, 2006; AD 142:620–624, 2006; AD 140:939–944, 2004; BJD 144:1284–1286, 2001; AD 132:1487–1490, 1996; AD 133:1111–1117, 1997; Ped Derm 6:82–90, 1989; BJD 66:104–111, 1954 Kniest syndrome – flat face, widely spaced eyes, flat nasal root, cleft palate Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 250–251

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Koraxitrachitic syndrome – self-healing collodion baby with residual mottled reticulated atrophy (dappled atrophy of dermis); alopecia, absent eyelashes and eyebrows, conjunctival pannus, hypertelorism, prominent nasal root, large mouth, micrognathia, brachydactyly, syndactyly of interdigital spaces Am J Med Genet 86:454–458, 1999 Laband syndrome (hereditary gingival fibromatosis) – soft, large floppy ears; bulbous soft nose, gingival fibromatosis; absent nails; atrophic distal phalanges, hyperextensible joints, hepatosplenomegaly, hypertrichosis, mental retardation Ped Derm 10:263–266, 1993; J Otol Pathol Med 19:385–387, 1990; Oral Surg Oral Med Oral Pathol 17:339–351, 1964 Lacrimo-Auricular-Dento-Digital syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 378–379 Larsen syndrome – flat, rectangular face with low nasal root, prominent forehead, hypertelorism Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 404–405 Legius syndrome – Noonan-like facial features, pulmonary stenosis, pectus abnormalities, learning disabilities Hum Mut 33:1538–1546, 2012; JAMA 302:2111–2118, 2009 Lelis syndrome – acanthosis nigricans with hypohidrosis, hypotrichosis with absent lower eyelashes, pubic and axillary hair absent, hystrix-like ichthyosis of axillae, hypodontia, furrowed tongue, hyperconvex nail dystrophy, palmoplantar keratoderma, vitiligo; facies including long narrow face with upslanting palpebral fissures, strabismus, proptosis, midface hypoplasia, perioral radial furrows and perioral hyperpigmentation, prognathism, hypodontia, furrowed tongue, high arched palate Ped Derm 33:563, 2016; Am J Med Genet 146:2155–2158, 2008; J Coll Physicians’ Surg Pak 14:626– 627, 2004; Am J Med Genet A 149:1612–1613, 2002; Am J Med Genet 113:381–384, 2002; Genetic Skin Disorders, Second Edition, 2010, pp. 94–97 Leprechaunism – (Donohue’s syndrome) – prominent eyes with shallow orbits; micrognathia; simian wizened appearance makes skin appear loose with excessive wrinkling; decreased subcutaneous tissue and muscle mass, characteristic facies, severe intrauterine growth retardation, broad nose, low set ears, hypertrichosis of forehead and cheeks, loose folded skin (redundant) at flexures, gyrate folds of skin of hands and feet; breasts, penis, clitoris hypertrophic; thickened skin around lips and genitalia Endocrinologie 26:205–209, 1988 LEOPARD syndrome – elongated facies with ocular hypertelorism; dark brown small lentigines over face; ptosis, epicanthal folds, irregular iris pigmentation, congenital sensorineural deafness Lipoid proteinosis- candle wax (cobblestoned) appearance of skin of face Genetic Skin Disorders, Second Edition, 2010, pp. 484–489 Lissencephaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 84–85 Loeys-Dietz syndrome – dysmorphic facies – marfanoid habitus, delicate triangular face, multiple facial milia, velvety and translucent skin, easy bruising, varicose veins, atrophic scars, malar hypoplasia, retrognathia, craniosynostosis, hypertelorism, cleft lip and palate, bifid uvula, malar hypoplasia, blue sclerae,; atrophoderma vermiculatum, milia; wide aortic root and pulmonary artery; patent ductus arteriosus, sagittal craniodysostosis, thoracic scoliosis, lordosis, pectus excavatum, long extremities, vertical talus, varus deformity, hyperlaxity, amelogenesis imperfect, high arched palate, lobulated uvula; mutation in TGFBR2 JAMADerm 151:675–676, 2015 Lowe’s syndrome (oculo-cerebro-renal syndrome) – X-linked; clouding of lens at birth; proximal tubular dysfunction of Fanconi type; short stature, dental cysts

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Lymphedema-distichiasis syndrome – double row of eyelashes; nuchal webbing; downslanting palpebral fissures, ptosis; edema of the extremities Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high pitched voice; mutation in RIN2 JAAD 66:842–851, 2012 Macrocephaly-CMTC (cutis marmorata telangiectatica congenita syndrome) – renamed “macrocephaly-capillary malformation syndrome” – macrocephalic neonatal hypotonia and developmental delay; frontal bossing, segmental overgrowth, syndactyly, asymmetry, distended linear and serpiginous abdominal wall veins, patchy reticulated vascular stain without atrophy; telangiectasias of face and ears; midline reticulated facial nevus flammeus (capillary malformation) (vascular stains), hydrocephalus, skin and joint hypermobility, hyperelastic skin, thickened subcutaneous tissue, polydactyly, 2–3 toe syndactyly, post-axial polydactyly, hydrocephalus, frontal bossing, hemihypertrophy with segmental overgrowth; neonatal hypotonia, developmental delay Ped Derm 33:570–584, 2016; Ped Derm 24:555–556, 2007; Ped Derm 29:384–386, 2012; JAAD 63:805–814, 2010; Ped Derm 26:342–346, 2009; AD 145:287–293, 2009; JAAD 58:697–702, 2008; Ped Derm 24:555– 556, 2007; JAAD 56:541–564, 2007; Ped Derm 16:235–237, 1999; Genet Couns 9:245–253, 1998; Am J Med Genet 70:67–73, 1997; Clin Dysmorphol 6:291–302, 1997; (Note: Beckwith-Wiedemann syndrome demonstrates dysmorphic ears, macroglossia, body asymmetry, midfacial vascular stains, visceromegaly with omphalocele, neonatal hypoglycemia, BUT NO MACROCEPHALY) Macrocephaly with intracranial arteriovenous shunt Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 34–35 Mal de Meleda – hyperkeratotic perleche Mandibuloacral dysplasia – autosomal recessive; progeroid facies; facial asymmetry, micrognathia, small nose, prominent eyes, large open fontanelles; congenital brown pigmentation of ankles progresses to mottled pigmentation; hypoplastic clavicles; contractures of lower extremities; failure to thrive; progressive glomerulopathy; subcutaneous calcified nodules; mutation in ZMPSTE24 (lamin) JAMADerm 151:561–562, 2015 Marfan’s syndrome – high arched palate, crowded teeth, extreme nearsightedness (ectopia lentis) Marfanoid habitus with long face, hypotelorism; long, thin nose; long, thin hands and feet; language and learning disabilities Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) – autosomal recessive; coarse facies; corneal clouding, endocardial fibroelastosis with cardiomyopathy, dysostosis multiplex Ped Derm 33:594–601, 2016; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 126–127 Martsolf syndrome – cataracts, facial dysmorphism, microcephaly, short stature, hypogonadism Am J Med Genet 1:291–299, 1978; Syndromes of the Head and Neck, p. 906, 1990 Mastocytosis, systemic – premature aged facial appearance due to pruritus and rubbing Ped Derm 19:184–185, 2002 MC/MR syndrome with multiple circumferential skin creases – multiple congenital anomalies including high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals, posteriorly angulated ears, short stature, hypotonia, pectus excavatum, inguinal and umbilical hernias, scoliosis, hypoplastic scrotum, long fingers, overlapping toes, severe psychomotor

retardation, resembles Michelin tire baby syndrome Am J Med Genet 62:23–25, 1996 Meckel-Gruber syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 82–83 Megalencephaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 36–37 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome – macrocephaly, face and limb asymmetry, craniofacial abnormalities, joint laxity or soft skin, distal limb malformation; developmental delay, Nat Genet 44:934–940, 2012; Ped Derm 30:541–548, 2013 Melkersson-Rosenthal syndrome – orofacial edema Melnick-Needles syndrome – exophthalmos; full cheeks, micrognathia, malalignment of teeth; lethal in male infants; mutation in FLNA MEND – X-linked recessive; hypomorphic mutation of emopamil-­ binding protein; diffuse mild ichthyosis; telecanthus, prominent nasal bridge, low set ears, micrognathia, cleft palate large anterior fontanelle, polydactyly, 2–3 syndactyly, kyphosis, Dandy-Walker malformation, cerebellar hypoplasia, corpus callosal hypoplasia, hydrocephalus, hypotonia, developmental delay, seizures; bilateral cataracts, glaucoma, hypertelorism; cardiac valvular and septal defects, hypoplastic aortic arch; renal malformation, cryptorchidism, hypospadias BJD 166:1309–1313, 2012 Menkes’ syndrome – puffy face with pudgy cheeks (cutis laxa-like), horizontal eyebrows, cupid’s bow of upper lip, short blond hair with pili torti; prolonged hypothermia, pectus excavatum, umbilical and inguinal hernias; loose skin with wrinkling Ped Derm 14:347–350, 1997; silvery hair, generalized hypopigmentation, lax skin of brows, neck, and thighs Ped Derm 15:137–139, 1998; bone fractures with Wormian bones, cervical bone abnormalities, rib fractures, spurring of long bone metaphyses mimicking child abuse Society Pediatric Dermatology Annual Meeting, July, 2015; Pediatr Radiol 42:1301– 1304, 2012; Cutis 90:170–172, 2012; Arg Neurosiquiatr 67:507– 509, 2009; Arch Dis Child 91:919, 2006 Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes (dermatitis), congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321– 327, 1996 Mesomelic dysplasia type Langer Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 204–205 Metageria – autosomal recessive; dry, atrophic, mottled skin, pinched face with beaked nose Hautarzt 48:657–661, 1997; BJD 91:243–262, 1974 Metaphyseal dysplasia Wiedemann-Spranger type – antimongoloid slant of palpebral fissures Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 266–267 Michelin tire baby syndrome – either nevus lipomatosis or diffuse smooth muscle hamartoma; degenerative collagen, scarring; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques; low set malformed ears with thickened helix and anti-helix; wide or depressed nasal bridge; epicanthal folds, hypertelorism, cleft palate, micro-ophthalmia or deep set eyes, flat or hypoplastic midface, short neck, decreased hearing, hypoplastic malformed genitalia, micrognathia, histologically increased periadexal fat and subcutaneous fat and smooth muscle hamartomas; mental retardation, tendinous hyperlaxity, seizures, mastocytosis, complex malformations syndrome (bilateral calcaneovalgus deformity, cleft palate, inguinal hernia, hip deformity, clefting of lateral mouth commissures, shawl scrotum, absent foreskin; developmental delay, microcephaly, mental retardation Ped Derm 31:659–663, 2014; JAAD 63:1110–1111, 2010; Ped Derm 27:79–81, 2010; Ped

Facies Derm 24:628–231, 2007; Ped Derm 22:245–249, 2005; Ped Derm 20:150–152, 2003; BJD 129:60–68, 1993; JAAD 28:364–370, 1993; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 308–309; Ped Derm 6:329–331, 1989; Am J Med Genet 28:225–226, 1987; AD 115:978–979, 1979; diffuse lipomatous hypertrophy AD 100:320–323, 1969; generalized muscular nevus Ann DV 107:923–927, 1980 Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation (nevus depigmentosus); small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Microphthalmia with linear skin defects syndrome (MLS syndrome) (microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome) – X-linked dominant; atrophic Blaschko linear scars of face and neck; linear red atrophic skin (resembles aplasia cutis) Am J Med Genet 124A:202–208, 2004; Am J Med Genet 49:229–234, 1994 Mietens syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 180–181 Mitochondrial myopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 498–499 Mobius sequence – expressionless face facial paralysis; inability to move the eyes from side to side; cannot close eyes; upper lip often retracted Morquio’s syndrome (MPS IV) – corneal clouding, hearing loss; bell shaped chest Moore-Federman syndrome – short stature, stiffness of joints, characteristic facies J Med Gen 26:320–325, 1989 MORFAN syndrome – mental retardation, prenatal and postnatal overgrowth, peculiar facies, acanthosis nigricans JAAD 57:502–508, 2007; Am J Med Genet 45:525–528, 1993 Mucoepithelial dysplasia (gap junction disease) – perleche, squinting eyes with photophobia due to keratitis Genetic Skin Disorders, Second Edition, 2010, pp. 698–700 Mucolipidosis – mountain range folding of facial skin Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 134–135 Mucopolysaccharidosis type IX – autosomal recessive; hyaluronidase 1 deficiency; soft tissue masses, short stature, coarse facies, hypertrichosis, synophrys; accumulation of hyaluronic acid Ped Derm 33:594–601, 2016 Multiple endocrine neoplasia syndrome – elongated slender face with full lips; neuromas of mucosa, thickened blubbery or irregular appearance to lips; eyelids, tongue, conjunctiva may be involved Multiple sulfatase deficiency – autosomal recessive; broad thumbs, mild ichthyosis, gargoylism, mental retardation, mucopolysaccharidosis BJD 147:353–355, 2002; Ped Derm 18:388–392, 2001; Ped Derm 14:369–372, 1997

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Myhre syndrome – low birth weight, short stature, muscular build, limited joint mobility, cardiac defects, deafness, skeletal abnormalities, facial dysmorphism, thick skin, keratosis pilaris, coarse facies Nager acrofacial dysostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 50–51 Naxos syndrome – personal observation Neu-Laxova syndrome – taut, shiny, sclerodermoid face with absent eyelids, eclabian (resembling harlequin fetus); prominent bulbous nose later Genetic Skin Disorders, Second Edition, 2010, pp. 130–132 Neurofibromatosis type 1-like (NF-1-like) (Legius syndrome) – autosomal dominant; multiple café-au-lait macules, axillary freckling, macrocephaly; Noonan-like dysmorphic changes; mutation in SPRED-1 gene; SJPRED-1 protein negatively regulates Ras-mitogen-activated protein kinase (MAPK) JAAD 147:735–740, 2011; JAMA 302:2111–2118, 2009; Nat Genet 39:1120–1126, 2007 Nevoid basal cell carcinoma syndrome (Gorlin's syndrome) – autosomal dominant; dysmorphic facies, smooth surfaced rounded papules 1–15 mm; epidermoid cysts and milia; diffuse palmoplantar hyperkeratosis; palmoplantar punctate hyperkeratosis with pits; odontogenic keratocysts; bifid ribs; spina bifida occulta, kyphoscoliosis; broad nasal root, hypertelorism, frontal bossing, syndactyly, calcification of falx cerebri, defective dentition, neurologic and eye abnormalities; abnormal renal resorption of phosphate BJD 182:212–217, 2020; Am J Med Genet 50:282–290, 1994; Medicine 66:98–113, 1987 Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, prenatal onset short stature, growth retardation, bird-like facies with epicanthal folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of face, café au lait macules, vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair 3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000; Am J Med Genet 66:378–398, 1996 Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, prenatal onset short stature, growth retardation, bird-like facies with epicanthal folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of face, café au lait macules, vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair 3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000; Am J Med Genet 66:378–398, 1996

Myotonic dystrophy Curschmann-Steinert Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 504–505

Noonan's syndrome – short webbed neck, short stature, low set, backward rotated malformed ears, high arched palate, poor teeth alignment, micrognathia, nevi, keloids, transient lymphedema, ulerythema ophyrogenes, keratosis follicularis spinulosa decalvans; ocular hypertelorism, deep groove philtrum, pectus excavatum, scoliosis; RASopathy with 50% of cases due to PTPN11 gene; other genes SOS1, RAF1, RIT1 JAAD 46:161–183, 2002; J Med Genet 24:9–13, 1987; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 196–197

Myotubular (centronuclear) myopathy – sleepy face Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 496–497

Oculocutaneous albinism, dysmorphic features, short stature Ophthalmic Paediatr Genet 11:209–213, 1990

Mulvihill-Smith syndrome – short stature, microcephaly, unusual facies, multiple pigmented nevi, hypodontia, immunodeficiency with chronic infections, high pitched voice, progeroid, conjunctivitis, delayed puberty J Med Genet 31:707–711, 1994 Myasthenia gravis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 502–503

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Oculo-dento-osseous dysplasia – long thin nose, hypoplastic nose and narrow nostrils Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 422–423

Panhypopituitary dwarfism – short stature, excess subcutaneous fat, high pitched voice, soft, wrinkled skin, child-like facies Birth Defects 12:15–29, 1976

Oculo-ectodermal syndrome – macrocephaly, cutis aplasia, abnormal pigmentation, scalp nodules, corneal epibulbar dermoid cysts BJD 151:953–960, 2004; Bolognia, p. 924, 2003

Parry-Romberg syndrome JAAD 67:769–784, 2012; JAAD 56:257–263, 2007; Ped Derm 21:48–50, 2004; Hautarzt 47:599– 603, 1996; JAAD 22:531–533, 1990; Arch Neurol 39:44–46, 1982;Klinische Ergebnisse. Berlin. Forstner; 1846. pp. 75–81

Olmsted syndrome – verrucous plaques of nasolabial folds, folds of chin with alopecia; TRPV3 mutation; perioral, perinasal, chin hyperkeratotic fissured plaques, progressive; oral leukokeratosis, alopecia, severe pruritus, palmoplantar keratoderma Opitz trigonocephaly syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 20–21 Oro-acral syndrome (aglossia-adactyly syndrome, ankyloglossia superior syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 380–381 Oral-facial-digital syndrome type 1 (Papillon-League-Psaume syndrome) – X-linked dominant; congenital facial milia which resolve with pitted scars; milia of face, scalp, pinnae, and dorsal hands; short stature, hypotrichosis with dry and brittle hair, short upper lip, hypoplastic ala nasi and lower jaw, pseudoclefting of upper lip, hooked pug nose, hypertrophied labial frenulae, bifid or multilobed tongue with small white tumors within clefts, ankyloglossia, multiple soft hamartomas of oral cavity, clefting of hard and soft palate, teeth widely spaced with dental caries, trident hand or brachydactyly, syndactyly, clinodactyly, ulnar deviation of index finger, or polydactyly; hair dry and brittle, alopecic, numerous milia of face, ears, backs of hands, mental retardation with multiple central nervous system abnormalities, frontal bossing, hypertelorism, telecanthus, broad depressed nasal bridge; polycystic renal disease; combination of polycystic renal disease, milia, and hypotrichosis is highly suggestive of OFD 1 Ped Derm 27:669–670, 2010; JAAD 59:1050– 1063, 2008; Ped Derm 25:474–476, 2008; Ped Derm 9:52–56, 1992; Am J Med Genet 86:269–273, 1999; JAAD 31:157–190, 1994; Ped Derm 9:52–56, 1992; Pediatrics 29:985–995, 1962; Rev Stomatol 55:209–227, 1954 Orofacial digital syndrome type II – absence of milia, bilateral duplication of hallux; short stature, abnormal central incisors, normal intelligence Osteodysplastic geroderma (Walt Disney dwarfism) – short stature, cutis laxa-like changes with drooping eyelids and jowls, osteoporosis and skeletal abnormalities Am J Med Genet 3:389–395, 1979 Osteogenesis imperfecta Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 366–369 Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, immunodeficiency (OL-HED-ID) syndrome – X-linked recessive; mutation of NEMO Ped Derm 31:716–721, 2014 Oto-palato-digital syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 26–27 Pachydermoperiostosis Pallister-Killian (Killian-Teschler-Nicola syndrome) syndrome – short neck; Blaschko hyperpigmentation, streaks of hypo- and hyperpigmentation, mental retardation, coarse facies with prominent forehead with abnormally high anterior hairline, sparse temporal hair and sparse anterior scalp hair, hypertelorism, short nose with anteverted nostrils, flat nasal bridge, flat occiput, chubby cheeks, sparse eyelashes, long philtrum with thin upper lip, horizontal palpebral fissure, large low set ears with thick lobules, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i (12p) (tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 24:426–428, 2007; Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005; Ped Derm 17:151–153, 2000

Parrot syndrome (chondrodysplasia fetalis) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 234–235 Parry-Romberg syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 56–57 Patterson David syndrome – pseudoleprechaunism Patau’s syndrome (non-mosaic trisomy 13) – parieto-occipital scalp defects, cleft lip/palate, abnormal helices, low set ears, loose skin of posterior neck, simian crease of hand, hyperconvex narrow nails, polydactyly, microcephaly, microphthalmia, severe central nervous system anomalies, congenital heart defects, holoprosencephaly; death in first year Am J Med Genet 143A:1739–1748, 2007; Ped Derm 22:270–275, 2005 Peculiar facies and marfanoid habitus with psychomotor retardation Clin Genet 25:187–190, 1984 Peeling skin syndrome autosomal recessive group of genodermatoses; generalized inflammatory and non-inflammatory and acral Ped Derm 37:371–372, 2020 Penttinen syndrome – progeroid disorder with overgrowth; resembles mandibuloacral dysplasia (which has micrognathia); hypertelorism, malar hypoplasia, prognathia, narrow nose; open font, shallow orbits, lipoatrophy with thin translucent skin; scars overlying joints; acroosteolysis Am J Med Genet A 161A:1786–1791, 2013; Am J Med Genet 69:182–187, 1997 Perlman syndrome – micropenis; nephroblastoma, renal hamartoma, facial dysmorphism, fetal gigantism J Pediatr 83:414–418, 1973 Pfeiffer syndrome (acrocephalosyndactyly type Pfeiffer Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 16–17 PHACES syndrome – midline sternal notch; cervicofacial hemangioma; structural arterial brain malformations EurJ Pediatr Jan, 2007; JAAD 55:1072–1074, 2006; BJD 155:192–194, 2006; Clin Pediatr 44:747, 2005 Piebaldism – triangular shaped or diamond shaped white forelock; may extend to involve medial third of eyebrows; chin often involved; islands of hyperpigmentation within depigmented patches Pierpont syndrome – X-linked or autosomal dominant; plantar lipomatosis, abnormal facies (high forehead, high anterior hairline, mild midfacial hypoplasia, remarkably narrow and upward slanted palpebral fissures, broad nasal ridge and tip, broad philtrum, bowed upper lip, pouting upper lip, full cheeks, and flat occiput), developmental delay Am J Med Genet A 137:77–80, 2005 Pierre-Robin anomaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 68–69 Porphyrias – congenital erythropoietic porphyria; erythropoietic protoporphyria; porphyria cutanea tarda Genetic Skin Disorders, Second Edition, 2010, pp. 618–620 POEMS syndrome – personal observation Poikiloderma, alopecia, retrognathism, and cleft palate (PARC syndrome) Dermatologica 181:142–144, 1990 Potter syndrome (oligohydramnios, facial dysmorphism) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 76–79 Prader-Willi syndrome – round obese face Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 286–287

Facies

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Premature aging and short stature syndrome (Mulvihill-Smith syndrome) – loss of facial subcutaneous tissue

Genet 5:1–16, 1974; (tetraphocomelia-­cleft palate syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 372–373

Progeroid syndrome with cardiac anomaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 278–279

Robinow syndrome (fetal face syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 210–211

Progressive spastic parapesis, vitiligo, premature graying, and distinct facial appearance

Rothmund-Thomson syndrome – frontal bossing, saddle nose, prognathism, poikiloderma and alopecia JAAD 75:855–870, 2016;

Proteus syndrome – lipohypoplasia and patchy dermal hypoplasia AD 140:947–953, 2004; AD 133:77–80, 1997; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 352–355

Genomics 61:268–276, 1999

Pseudodiastrophic dysplasia Burgio type Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 238–239 Pseudohypoparathyroidism type Ia (Albright’s hereditary osteodystrophy) – subcutaneous nodule (osteoma cutis); short stature, round face, obesity, subcutaneous ossifications, bilateral brachydactyly, mental retardation, hypothyroidism, saddle nose deformity Ped Derm 33:675–676, 2016 PTEN-hamartoma-tumor syndrome – grossly enlarged hand; recurrent arteriovenous malformations of hand and forearm; macrocephaly, frontal bossing, café au lait macules, congenital nevi, low set ears, downward slanting eyebrows and palpebral fissures Ped Derm 28:466–467, 2011 Ptosis and unusual facies Am J Med Genet 7:5–9, 1980 PYCR1-related cutis laxa – hair loss, prominent scalp veins, triangular shaped face, microcephaly, short stature, hypermobility of joints, thin atrophic skin, wrinkled skin, muscle weakness, finger contractures Dtsch Arztebl Intl 16:489–496, 2019 Pyknodysostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 200–201 Rabenhorst syndrome – high narrow nose, mongoloid slant of palpebral fissures, microstomia, prognathism, adherent ear lobes, dolichocephaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 490–491 Rabson-Mendenhall syndrome (Miescher syndrome) – autosomal recessive; insulin resistant diabetes, acanthosis nigricans, coarse and senile appearance, precocious puberty J Indian Soc Endod Prev Dent 30:279–282, 2012; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 322–323 Raine syndrome – high forehead, proptosis, hypoplastic nose, absent nasal spine, long philtrum; cerebellar hypoplasia, generalized osteosclerosis, neonatal lethality; FAM20C gene Ramon syndrome – autosomal recessive; cherubism, gingival fibromatosis, epilepsy, mental deficiency, hypertrichosis, and stunted growth Rapp-Hodgkin ectodermal dysplasia – autosomal dominant; sparse hair, nails narrow and dystrophic, small stature, cleft lip or palate, hypospadius, conical teeth and hypodontia; distinctive facies Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968 Reticulolinear aplasia cutis congenita of the face and neck – Xp deletion syndrome, MIDAS (microphthalmia, dermal aplasia, sclerocornea), MLS (microphthalmia and linear skin defects), and Gazali-Temple syndrome; lethal in males; residual facial scarring in females, short stature, organ malformations BJD 138:1046–1052, 1998 Robert’s pseudothalidomide syndrome (hypomelia-hypotrichosisfacial hemangioma syndrome) (Roberts/SC phocomelia syndrome) – autosomal recessive; mid-facial port wine stain extending from forehead to nose and philtrum, cleft lip +/− cleft palate, sparse silver-blond hair, limb reduction malformation, characteristic facies, malformed ears with hypoplastic lobules, micrognathia; hypoplastic nares, marked growth retardation JAAD 56:541–564, 2007; Curr Probl Dermatol 3:69–107, 1995; Clin Genet 31:170–177, 1987; Clin

Rubenstein-Taybi syndrome – arciform keloids, hypertrichosis, long eyelashes, thick eyebrows, keratosis pilaris or ulerythema ophyrogenes, low set ears, very short stature, broad terminal phalanges of thumbs and great toes, hemangiomas, nevus flammeus, café au lait macules, pilomatrixomas, cardiac anomalies, mental retardation; mutation in CREBBP and EP300 BJD 171:615–621, 2014; Ped Derm 19:177–179, 2002; Am J Dis Child 105:588–608, 1963 Ruijs-Aalfs syndrome – premature aging and cancer predisposition syndrome; facial and skeletal abnormalities; hepatoma in teenage years; triangular face, small deep set eyes, micrognathia, small upper lip, bulbous nose; SPRTN gene Nature Genet 46:1239–1244, 2014 Russel syndrome (diencephalic tumor-emaciation syndrome of infancy) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 284–285 Russel-Silver syndrome – short stature, triangular shaped face, clinodactyly of fifth digit, macrocephaly Ped Derm 30:150–151, 2013 Saldino-Noonan short rib polydactyly syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 218–219 Sanfilippo’s syndrome (mucopolysaccharidosis type III) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 122–123 Saethre-Chotzen syndrome – craniosynostosis, small unusually shaped ears; high forehead, low frontal hairline, droopy eyelids, wide spaced eyes, broad nasal ridge, facial asymmetry SCARF syndrome – ambiguous genitalia associated with skeletal abnormalities, cutis laxa, joint hyperextensibility, webbed neck, craniostenosis, psychomotor retardation, and facial abnormalities Am J Med Genet 34:305–312, 1989 Schimmelpenning syndrome (nevus sebaceus syndrome) – hemimacrocephaly Schwart-Jampel syndrome – facial dysmorphism, muscle stiffness, hypertrichosis of eyelids Adv Biomed Res Aug 10, 2015 Seckel’s syndrome (bird-headed dwarfism) – autosomal recessive; abnormal teeth, short stature, hypopigmented papules and macules, small deformed ears lacking lobes, syndactyly, clinodactyly; hair sparse and prematurely gray, growth retardation, beak-like nose, large eyes, skeletal defects Ped Derm 24:53–56, 2007; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 168–169; Am J Med Genet 12:7–21, 1982 Seip-Berardinelli syndrome (congenital generalized lipodystrophy) – face appears haggard, abdomen protuberant; hypertrichosis of face and body; low frontal hairline, acanthosis nigricans Setleis syndrome (focal facial dermal dysplasia type III) – aged leonine appearance, bi-temporal scar-like defects, absent or multiple rows of upper eyelashes, eyebrows slanted up and out, scar-like median furrow of chin Ped Derm 24:555–556, 2007; BJD 130:645–649, 1994; Pediatrics 32:540–548, 1963; focal facial ectodermal dysplasia; scarring of the temples at birth Genetic Skin Disorders, Second Edition, 2010, pp. 282–284 Short stature, characteristic facies, mental retardation, skeletal anomalies, and macrodontia Clin Genet 26:69–72, 1984 Short stature, premature aging, pigmented nevi J Med Genet 25:53–56, 1988

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Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes, congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321–327, 1996 Shprintzen- Goldberg syndrome (velo-cardio-facial syndrome) – craniosynostosis, marfanoid habitus, hypertelorism, exophthalmos, down slanting palpebral fissures, high narrow palate, micrognathia, low set ears rotated backward, Hirschsprung disease Pan Afr Med J 23:227:2016; Hum Mutat 37:524–531, 2016 Simosa craniofacial syndrome – facial dimples Simpson-Golabi-Behmel syndrome (bulldog syndrome – X-linked recessive; macroglossia, protruding jaw and tongue, widened nasal bridge, upturned nasal tip, hands/feet short, broad dysplastic nails, supernumerary nipples, hypotonia Sirenomelia (mermaid syndrome) – legs fused together Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 80–81 Smith-Fineman-Myers syndrome (unusual facies, short stature, and mental deficiency) – head slightly smaller with unusual shape, narrow face, large mouth, drooping lower lip held open, protruding upper jaw, widely spaced upper front teeth, ptosis Am J Med Genet 22:301–304, 1985 Smith-Lemli-Opitz syndrome – autosomal recessive; deficiency of 7-dehydrocholesterol-7-reductase (converts 7-DHC to cholesterol so have increased 7-DHC and decreased cholesterol) – sunburn with photosensitivity to UVA, polydactyly, syndactyly of 2nd and 3rd toes, growth and mental retardation, failure to thrive, dysmorphic facies, cleft palate, congenital heart disease, hypospadias JAAD 67:1113–1127, 2012; AD 142:647–648, 2006; BJD 153:774–779, 2005; NEJM 351;2319–2326, 2004;BJD 144:143–145, 2001; Photodermato Photoimmunol Photomed 15:217–218, 1999; BJD 141::406–414, 1999; JAAD 41:121–123, 1999; Am J Med Genet 66:378–398, 1996 Am J Hum Genet 53:817–821, 1993; Clin Pediatr 16:665–668, 1977; J Pediatr 64:210–217, 1964; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 494–495 Smith Magenis syndrome – distinctive facial and skeletal features; self-injurious behaviors Ped Derm 32:337–341, 2015 Sotos syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 138–139 Sotos syndrome (cerebral gigantism) – distinctive facial appearance with long narrow face, high forehead, frontal bossing, flushed reddened cheek, small pointed chin, unusually large head, high hairline; susceptible to tumors Ped Derm 25:122–125, 2008 Sparse hair, prominent nose, small mouth, micrognathia, cleft palate, crumpled upper helices, digit anomaly, mild developmental delay Am J Med Genet 101:70–73, 2001 Spondyloepiphyseal dysplasia congenita – flat face Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 246–247 Stanescu osteosclerosis syndrome – short stature, brachycephaly, hypoplastic midface, ocular proptosis, micrognathia, brachydactyly, dense cortices of long bones J Genet Hum 29:129–139, 1981 Stevens- Johnson syndrome Stickler’s syndrome (arthro-ophthalmopathy) – flat asymmetric face with depressed nasal root and nose; mitral valve prolapse; distinctive facies – prominent eyes, small nose with scooped out facial appearance and receding chin, ocular problems, hearing loss, joint and skeletal problems Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 532–533 Stiff skin syndrome (congenital fascial dystrophy) – decreased facial expression JAAD 75:163–168, 2016 Symphalangis-brachydactyly syndrome with conductive hearing impairment – long, narrow face, broad nasal bridge, asymmetric

mouth with thin upper lip Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 424–425 Tay-Sachs disease (GM2 gangliosidosis) – doll-like face with translucent skin, trichomegaly, fine hair, pink facial color Tetanus – fixed spasmed expression (risus sardonicus) The Lancet 393:1657–1668, 2019 Tetrasomy 13q – long forehead, thick eyebrows, hypertelorism, broad nasal bridge, malposition of teeth, prominent central incisors with diastema, bilateral clinodactyly of fifth fingers Ped Derm 32:263–266, 2015 Thanatophoric dysplasia – large cranium, micromelia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 214–215 Thanatophoric dysplasia type II with cloverleaf skull Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 216–217 Treacher-Collins-Franceschetti syndrome (mandibulofacial dysostosis) – autosomal dominant; prominent nose, sunken cheeks, stretching of skin to side of neck, recessed chin, large down-turned mouth, widespaced eyes with antimongoloid slants, lateral coloboma of lower eyelids, absent eyelashes of lower lids, hairline extended to cheeks, small and crumpled pinnae, with skin tags or blind pits between tragus and angle of the mouth; hypoplastic or deformed teeth in older children Ped Derm 23:511–513, 2006; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 48–49 Trichodysplasia spinulosa – follicular papules, keratotic spines of face and ears; eyebrow and scalp alopecia; facial disfigurement; trichodysplasia-­associated polyoma virus JAAD 75:1–16, 2016 Trichorhinophalangeal syndrome type I – autosomal dominant; slow growing scalp hair; receding frontotemporal hairline with high bossed forehead; facial pallor, pear-shaped bulbous nose, elongated philtrum, thin upper lip, receding chin, tubercle of normal skin below the lower lip, distension and deviation with fusiform swelling of the PIP joints; brachydactyly of thumbs and great toes, clinodactyly; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, eyebrows sparse laterally, dense medially (signe de sourcil (sign of the eyebrow)), short stature; mutation in zinc finger nuclear transcription factor (TRPS1 gene) BJD 163:416–419, 2010; BJD 157:1021–1024, 2007; AD 137:1429–1434, 2001; JAAD 31:331–336, 1994; Ped Derm 10:385–387, 1993; Hum Genet 74:188–189, 1986; Helv Paediatr Acta 21:475–485, 1966 Trichorhinophalangeal syndrome type II (Langer-Giedion syndrome) – microcephaly with mental retardation, deep set eyes, exotropia, long nose with bulbous tip, broad nasal bridge, thick ala nasi, high palate, crowded teeth, micrognathia, long neck, short metacarpals, thin nails, small feet with brachydactyly, vaginal stenosis, short stature, thin sparse hair, very high hairline; bitemporal recession; early balding, men and women; long face, prominent ears, madarosis, cartilaginous exostoses, foot deformities, joint laxity; EXT gene BJD 171:1581–1583, 2014; BJD 157:1021–1024, 2007; Genetic Skin Disorders, Second Edition, 2010, pp. 225–228; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 408–409420–421 Trichothiodystrophy syndromes (Tay syndrome) – BIDS, IBIDS, PIBIDS – autosomal recessive; collodion baby, congenital erythroderma, sparse or absent eyelashes and eyebrows, sulfur deficient short brittle hair with tiger tail banding on polarized microscopy, trichomegaly, brittle soft nails with koilonychia, premature aging, very short stature, microcephaly, sexual immaturity, ichthyosis, photosensitivity, hypohidrosis, high arched palate, dysmyelination of white matter, bird-like facies, abnormal teeth with dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; recurrent

Facies infections with neutropenia; ocular abnormalities, osteopenia; socially engaging personality; mutation in one of 3 DNA repair genes (XPB, XPA, TTDA, or TTDN1 Ped Derm 32:865–866, 2015; JAAD 63:323–328, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Pediatrics 87:571–574, 1991; Am J Med Genet 35:566–573, 1990; JAAD 16:940–947, 1987; Eur J Pediatr 141:147–152, 1984 Triphalangism of first rays of hands, thrombasthenia, sensorineural hearing loss – hypertelorism, broad nasal root, prognathism Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 434–435 Trisomy 9 – short stature, bulbous nose, marked palmar folds, low set ears, long philtrum, thin lips, low palpebral folds, cryptorchidism, mental retardation Ped Derm 26:482–484, 2009 Trisomy 18 Complete trisomy 22 – primitive low-set ears, bilateral preauricular pit, broad nasal bridge, antimongoloid palpebral fissures, macroglossia, enlarged sublingual glands, cleft palate, micrognathia, clinodactyly of fifth fingers, hypoplastic fingernails, hypoplastic genitalia, short lower limbs, bilateral sandal gap, deep plantar furrows Pediatrics 108:E32, 2001 Tuberous sclerosis – adenoma sebaceum (angiofibromas), skin colored or red; collagenomas (shagreen patches) of forehead; acrochordon, dental pits, hamartomas of retina or mulberry lesions Turner’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 192–193 Ulerythema oophyrogenes – red cheeks and forehead with keratotic papules, alopecia with keratotic papules of eyebrows Ulnar-mammary syndrome – autosomal dominant; ulnar defects, nipple or apocrine gland hypoplasia; wide face, nasal base and tip, protruding chin; cardiac abnormalities TXB3 mutation Eplasty 27:14:ic35, e collection 2014, 2014 September Ultraviolet radiation – excess exposure to ultraviolet radiation (dermatoheliosis)

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neonatal teeth, slender limbs, large hands and feet with long fingers, large penis J Med Genet 34:433–437, 1997 Williams’ syndrome – premature laxity of skin, congenital heart disease (supravalvular aortic stenosis), “elfin facies” with baggy eyes, full cheeks, prominent lips, dental malocclusion, delayed motor skills, cocktail party personality J Pediatr 113:318–326, 1988 Wiedemann-Steiner syndrome – hypertrichosis, prominent forehead, low hairline, small ears, hypertelorism, bushy eyebrows, localized thickened cutaneous plaques; dwarfism, peripheral corneal opacities, coarse facial features Winchester syndrome – autosomal recessive; annular and serpiginous leathery thickenings of skin; arthropathy, gargoyle-like face, gingival hypertrophy, macroglossia, osteolysis (multilayered symmetric restrictive banding), generalized hypertrichosis, very short stature, thickening and stiffness of skin with annular and serpiginous thickenings of skin, multiple subcutaneous nodules; arthropathy of elbows, shoulders, knees, hip, and spine; osteopenia; corneal clouding, hypertrichosis, macroglossia, irregularly spaced supernumerary teeth; mutation in MMP14 JAAD 50:S53–56, 2004 Woodhouse-Sakati syndrome – autosomal recessive; triangular shaped face with prominent forehead, large low set ears, dystonia, hypotrichosis, with sparse eyebrows and eyelashes; alopecia, hypogonadism, diabetes mellitus, mental retardation, sensorineural deafness, extrapyramidal signs, low insulin-like growth factor 1; must be differentiated from congenital hypotrichosis; mutation in C2orf37 Ped Derm 31:83–87, 2014; Am J Med Genet 143:149–160, 2007; J Med Genet 20:216–219, 1983 Weaver syndrome – macrocephaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 140–141 Whistling face syndrome (Freeman-Sheldon syndrome) (FreemanBurian syndrome) (craniocarpotarsal dysplasia) – microstomia, pursed lips, H or V-shaped chin defect, prominent nasolabial folds Orphanet J Rare Dis Jan 10, 2014

Unusual facies, digital abnormalities, ichthyosis J Med Genet 26:339–342, 1989

Wiedemann-Rautenstrauch syndrome – neonatal progeroid syndrome Genetic Skin Disorders, Second Edition, 2010, pp. 644– 646; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 272–273

Unusual facies, lipodystrophy, joint contractures (Werner-like disorder) Hum Genet 83:209–216, 1989

Wildervanck syndrome (cervico-acoustic syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 298–299

Urban-Rifkin_Davis syndrome – autosomal recessive; flattened midface; wide nasal bridge long philtrum, micrognathia, hypertelorism, periorbital fullness, receding forehead; severe pulmonary, gastrointestinal, and genitourinary abnormalities; mutation in LTBP4 JAAD 66:842–851, 2012

Williams’ syndrome – elfin facies Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 484–485

Van der Woude syndrome (lower lip pits, cleft lip and palate syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 60–61 Velocardiofacial syndrome – short narrow eyelids J Craniofac Genet Dev Biol 4:39–46, 1984 Waardenburg syndrome – heterochromic irides, dystopia canthorum, white forelock early graying hair (premature canities), synophrys Werner’s syndrome (pangeria of the adult) – loss of subcutaneous tissue; bird-like facies, beak nose, sclerodermoid features, cataracts, glaucoma, thin gray hair loses its luster, balding; calcinosis cutis, ulcerations; spindly legs BJD 152:1030–1032, 2005; Ann N Y Acad Sci 908:167–179, 2000; Am J Med 108:143–152, 2000; AD 124:90–101, 1988; Cancer 54:2580–2586, 1984; AD 118:106–108, 1982; Medicine 45:177–221, 1966 Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – generalized lipoatrophy, macrocephaly, premature aging, wide open sutures, hypoplasia of facial bones, low set ears, beak shaped nose,

Wolf syndrome (chromosome 4p_ syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 94–95 Winchester syndrome – autosomal recessive; systemic hyalinosis with joint contractures JAAD 55:1036–1043, 2006; JAAD 50:S53– 56, 2004   Coarse facies   Dwarfism, corneal opacities   Osteoporosis, osteolysis   Rheumatoid-like joint destruction (carpal-tarsal osteolysis)   Gingival hypertrophy Ped Derm 23:458–464, 2006  Hyperpigmentation (patches of thickened hyperpigmented and hypertrichotic skin)  Hypertrichosis (patches of thickened hyperpigmented and hypertrichotic skin)  Thickening of the skin (patches of thickened hyperpigmented and hypertrichotic skin)  Widespread nodular lesions J Med Genet 26:772–775, 1989; Am J Med Genet 26:123–131, 1987; J Pediatr 84:701–709, 1974; Pediatrics 47:360–369, 1971 Wolf-Hirschhorn (4p deletion) syndrome (oculocerebrocutaneous syndrome) – growth and mental retardation with seizures, micro-

420 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 cephaly, hypospadius, cryptorchidism, facial and ear abnormalities, down-turned mouth with cleft lip and/or palate and short philtrum Ped Derm 17:391–394, 2000

Sturge-Weber syndrome – port wine stain along ophthalmic or maxillary segment of trigeminal nerve; unilateral, present at birth without changing with age

Woolly hair, alopecia, premature loss of teeth, nail dystrophy, reticulate acral hyperkeratosis, facial abnormalities BJD 145:157– 161, 2001

DROOPY FACIES

Wrinkly skin syndrome – autosomal recessive Clin Genet 38:307– 313, 1990; same as cutis laxa with growth and developmental delay; increased palmoplantar creases, prominent venous pattern over chest, mental retardation, microcephaly, hypotonia (joint laxity), musculoskeletal (decreased muscle mass, hip dislocation, winging of scapulae, vertebral deformities), short stature, craniofacial abnormalities, and connective tissue abnormalities Ped Derm 23:225–230, 2006; Am J Med Genet 101:213–220, 2001; Ped Derm 6:113–117, 1999; Am J Med Genet 85:194, 1999; Clin Genet 4:186–192, 1973

Differential diagnosis of acquired bilateral peripheral facial palsy J Gen Intern Med 21:C7-C10, 2006

X-linked ectodermal dysplasia with immunodeficiency – NEMO mutation; erythroderma, alopecia, red scaly scalp, frontal bossing, periorbital wrinkling, intertrigo, thick everted lower lip AD 144:342– 346, 2008

Lyme disease – Banwarth’s syndrome

X-linked reticulate pigmentary disorder with systemic manifestations (familial cutaneous amyloidosis) – arched eyebrows, upswept frontal hairline, reticulate hyperpigmentation, palmoplantar keratoderma in males; respiratory infections, diarrhea, hypospadias, hypohidrosis, photophobia, corneal dystrophy Ped Derm 32:871–872, 2015; Am J Med Genet 161:1414–1420, 2013; Eur J Dermatol 18:102–103, 2008; Ped Derm 22:122–126, 2005; Am J Med Genet 10:65–75, 1981

Brainstem encephalitis

XYY syndrome – macrocephaly, taller than average, acne, severe learning disability; asymmetric cranium, dysplastic ears, epicanthus, strabismus, micrognathia

INFECTION Bell’s palsy Post-influenza Infectious mononucleosis HIV infection Guillain-Barre syndrome Syphilis HTLV-1 infection Poliomyelitis

INFITRATIVE DISORDERS Amyloidosis

INFLAMMATORY DISEASES

Xeroderma pigmentosum – conjunctivitis; acute sunburn, persistent erythema, freckling – initially discrete, then fuse to irregular patches of hyperpigmentation, dryness on sun-exposed areas; with time telangiectasias and small angiomas, atrophic white macules develop; vesiculobullous lesions, superficial ulcers lead to scarring, ectropion; multiple malignancies; photophobia, conjunctivitis, ectropion, symblepharon, neurologic abnormalities; short stature, conjunctivitis, photophobia, pyogenic granulomas in toddlers BJD 172:1096–1102, 2015; BJD 168:1109–1113, 2013; JAAD 59:881–886, 2008; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 330–331; BJD 152:545–551, 2005; Adv Genet 43:71–102, 2001; Hum Mutat 14:9–22, 1999; Mol Med Today 5:86–94, 1999; Derm Surg 23:447– 455, 1997; Dermatol Clin 13:169–209, 1995; Recent Results Cancer Res 128:275–297, 1993; AD 123:241–250, 1987; Ann Int Med 80:221–248, 1974; XP variant AD 128:1233–1237, 1992

Multiple sclerosis

Xp microdeletion syndrome – linear skin defects of head and neck (congenital smooth muscle hamartomas) (MIDAS syndrome – microphthalmia, dermal aplasia, sclerocornea) Ped Derm 14:26–30, 1997

Acute leukemia

Zellweger’s syndrome (cerebro-hepato-renal syndrome) – autosomal recessive; mutations in genes that encode peroxisomes; craniofacial anomalies – high forehead, hypoplastic supraorbital ridges, epicanthal folds, mid-face hypoplasia, large fontanelle, broad nasal bridge, chondrodysplasia punctate, renal cysts, hepatomegaly

Sarcoidosis The Neurologist 16:2–15, 2010

METABOLIC DISEASES Diabetes mellitus Acute porphyria Pseudobulbar and bulbar palsy Parkinson’s disease

NEOPLASTIC DISORDERS Acoustic neuroma

 ETAL AKINESIA DEFORMATION F SEQUENCE Cerebro-oculo-facio-skeletal syndrome Lethal multiple pterygium syndromes Neu-Laxova syndrome

VASCULAR LESIONS

Parana hard skin syndrome

Cystic hygroma (lymphatic malformation) – associated with Down’s syndrome, Turner’s syndrome, Noonan’s syndrome

Restrictive dermopathy

Leukocytoclastic vasculitis mimicking fixed drug eruption – personal observation

Pena-Shokeir syndrome

Fever and Rash, Noninfectious

FEVER AND RASH, NONINFECTIOUS  UTOIMMUNE DISEASE AND DISEASES A OF IMMUNE DYSREGULATION A2 haploinsufficiency (HA 20) – loss of function mutation in TNF AIP3 – mimics pediatric Behcet’s disease Ped Derm 33:602–614, 2016 APLAID – early onset recurrent erythematous plaques and vesicopustular skin lesions, arthralgias, corneal erosions, interstitial pneumonia Autoinflammatory syndrome with lymphedema (AISLE) – fever and urticarial, progressive edema of scrotum and legs; mutation in MyoD family inhibitor domain-containing protein Ped Derm 33:602–614, 2016 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – proteasome associated inflammatory syndrome; recurrent annular red or violaceous plaques which evolve to purpura then hyperpigmentation, purple swollen eyelids and lips, arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular episcleritis, lymphadenopathy, ear and nose chondritis, epidydimitis, cold-induced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, conjunctivitis; PSMB8 mutation Ped Derm 33:602–614, 2016 Cryopyrin-associated periodic syndromes (CAPS) – urticarial-like eruptions, fever, distal arthralgia, neurologic symptoms, eye disease, amyloidosis Ped Derm 33:602–614, 2016; JAAD 68:834– 853, 2013   Familial cold autoinflammatory syndrome   Muckle-Wells syndrome   Neonatal-onset multisystem inflammatory disease (NOMID) DADA2 (deficiency of adenosine deaminase 2) – autosomal recessive; intermittent recurrent fevers, early onset lacunar stroke, livedo racemosa, polyarteritis nodosa, hepatosplenomegaly; mutation in CECR1 Ped Derm 33:602–614, 2016; JAAD 75:449– 453, 2016; vasculopathy associated with mutations in ADA2 – syndrome of livedoid rash, intermittent fevers, early onset lacunar strokes and other neurovascular manifestations, hepatosplenomegaly, and systemic vasculopathy; loss of function mutations in CECR1 NEJM 370:911–920, 2014 Early onset inflammatory bowel disease Clin Immunol 147:155–174, 2013 Engraftment syndrome – fever or skin rash with neutrophil recovery Eur J Hematol 96:517–526, 2016 Familial cold autoinflammatory syndrome (cold urticaria) (FCAS) – autosomal dominant; non-pruritic urticarial (papules and plaques) rash precipitated by cold lasting 12 hours; ocular pain, conjunctivitis, blurred vision, arthralgias of knees and ankles and arthritis; fever and rash more severe in evening; abdominal pain, headache, nausea, sweating, drowsiness, extreme thirst, mutation in gene encoding NALP3 (cryopyrin); CIAS1 JAAD 68:834–853, 2013; AD 144:392–402, 2008; Ped Derm 24:85–89, 2007; AD 142:1591– 1597, 2006; JAAD 54:319–321, 2006; BJD 150:1029–1031, 2004; JAMA 114:1067–1068, 1940 Familial Mediterranean fever – autosomal recessive; painful erysipelas-­like erythema of extensor arms, legs, and feet; mutation in MEFV Ped Derm 33:602–614, 2016 Inflammatory bone diseases Ped Derm 33:602–614, 2016   Deficiency of IL-1 receptor antagonist (DIRA)  Chronic multifocal osteomyelitis – deficiency of IL-36 antagonist (DITRA)

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 Majeed syndrome – autosomal recessive; loss of function mutation of LPIN2; neonatal onset recurrent multifocal osteomyelitis, neutrophilic dermatosis, congenital dyserythropoietic anemia Gain of function mutation of NLRC4 (inflammasome) – fever, periodic urticarial rash, conjunctivitis, arthralgias, painful red nodules of foot or leg, enterocolitis, splenomegaly, macrophage activation syndrome; increased IL-18 BJD 176:244–248, 2017; Nat Genet 46:1135–1139, 2014; Nat Genet 46:1140–1146, 2014; J Exp Med 211:2385–2396, 2014 HOIL-1 deficiency – bloody diarrhea, erythroderma, dermatitis, severe recurrent pyogenic infections (fungal, viral) Clin Immunol 147:155–174, 2013 Juvenile rheumatoid arthritis (Still's disease) Med Chir Trans 80:47, 1897 Juvenile systemic granulomatosis (Blau syndrome, early onset sarcoid) Ped Derm 33:602–614, 2016 Lupus erythematosus – systemic; discoid lupus erythematosus NEJM 269:1155–1161, 1963 Macrophage activation syndrome Ped Derm 33:602–614, 2016   Systemic onset juvenile idiopathic arthritis   Adult-onset Still’s disease   Primary familial hemophagocytic lymphohistiocytosis Mevalonate kinase deficiency (Hyper IgD with periodic fever syndrome (HID syndrome) Ped Derm 33:602–614, 2016 Mevalonic aciduria Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) Rheumatol Int 39:957–970, 2019; Clin Dermatol 34:482– 486, 2016; Ped Derm 33:602–614, 2016 Periodic fever, immunodeficiency, and thrombocytopenia – severe oral ulcers leading to scarring and microstomy; fever, poor growth, infections, thrombocytopenia Ped Derm 33:602–614, 2016 PLAID – cold-induced urticarial, susceptibility to infections, autoimmune manifestations PLCG2-associated diseases Ped Derm 33:602–614, 2016  PLCG2- associated antibody deficiency and immune dysregulation (APLAID)  Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation Pyogenic diseases Ped Derm 33:602–614, 2016   Deficiency of IL-36R antagonist (DITRA)  Familial psoriasis (PSORS2); CAMPS; CARD14 mediated psoriasis  Pyogenic sterile arthritis, pyoderma gangrenosum, acne vulgaris (PAPA) – PSTPIP-1 associated Relapsing polychondritis J Rheumatol 44:1098, 2017; Medicine (Balt)96:e8734, 2017; Case Rep Med 2016 PMID 26981127 Schnitzler’s syndrome Ped Derm 33:602–614, 2016 Serum sickness NEJM 311:1407–1413, 1984; Dermatol Clin 3:107–117, 1985; associated with hepatitis B Arch Int Med 141:623–629, 1981 Systemic-onset juvenile idiopathic arthritis (Still’s disease) – spiking fevers, daily evanescent morbilliform eruption, polyarticular arthritis JAAD 68:834–853, 2013; salmon-pink urticaria-like lesions JAAD 50:813–814, 2004; adult onset Still’s disease – urticaria and angioedema J Eur Acad Dermatol Venereol 19:360–363, 2005;– episodic fevers, polyarticular arthritis of both large and small joints; typical rash – evanescent salmon pink urticarial rash with fever on trunk, proximal extremities, pressure areas, face; atypical rash persistent eruption, periorbital edema, dermatomyositis-like rash; heliotrope AD 148:947–952, 2012; severe periorbital

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edema Rheumatol Int 32:2233–2237, 2012; Ped Derm 21:580– 588, 2004; Clin Rheumatol 22:89–93, 2003; Semin Hop 59:1848– 1851, 1983

Lymphoma – subcutaneous panniculitis-like T-cell lymphoma Dermatol Online J Feb 18, 2014 PMID 24612568; Hodgkin’s disease Intern Med 57:1145–1149, 2018

Tumor necrosis factor receptor associated periodic fever (TRAPS) Ped Derm 33:602–614, 2016

PRIMARY CUTANEOUS DISEASES DRUGS

Acne fulminans JAAD 28:572–579, 1993; Clin Rheumatol 5:118– 123, 1986

Azathioprine hypersensitivity reaction – occurs within first four weeks of treatment; fever, malaise, arthralgias, myalgias, nausea, vomiting, diarrhea; morbilliform eruption, leukocytoclastic vasculitis, acute generalized exanthematous pustulosis, erythema nodosum, Sweet’s syndrome Clin Inf Dis 68:1427–1430, 2019; JAAD 65:184–191, 2011

Erythrokeratolysis hiemalis (Oudsthoorn disease) (keratolytic winter erythema) – palmoplantar erythema, cyclical and centrifugal peeling of affected sites, targetoid lesions of the hands and feet – seen in South African whites; precipitated by cold weather or fever BJD 98:491–495, 1978

DRESS syndrome – fever, eosinophilia, death; multiple drugs; minocycline; giant cell myocarditis, eosinophilic myocarditis Cutis 93:107–110, 2014; drug hypersensitivity syndrome AD 132:1315– 1321, 1996

Febrile pityriasis rossea – personal observation

Minocycline hypersensitivity syndrome or lupus-like syndrome Br Med J 312:169–172, 1996; BJ Rheumatol 674–676, 1994; Minocycline-induced p-ANCA+ cutaneous polyarteritis nodosa (vasculitis) JAAD 48:311–340, 2003; JAAD 44:198–206, 2001 Propylthiouracil vasculitis – blue necrotic ear lesions; fever, arthralgias, and myalgias JAMADerm 151:551–552, 2015

Febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta Ped Derm 31:525–527, 2014; J Rheumatol 16:387–389, 1989 Urticaria multiforme – large polycyclic and annular wheals with dusky centers, acral and facial angioedema Ped Derm 28:436–438, 2011; fever, arcuate, annular, polycyclic lesions; ecchymotic center or central pallor; edema of hands and feet; aged 4 months to 4 years Cutis 89:260:262–264, 2012; Pediatrics 119:e1177–1183, 2007

SYNDROMES INFLAMMATORY DISORDERS Erythema multiforme MMWR 65:1–44, May 23, 2016; StevensJohnson syndrome MMWR 65:1–44, May 23, 2016 Febrile idiopathic lobar panniculitis of childhood – abdominal pain, arthralgia, fever, red nodules of face, legs, trunk, lipoatrophy Ped Derm 31:652, 2014 Neutrophilic sebaceous adenitis – annular expanding red plaques of face and back with fever, lymphadenopathy JAMADerm 150:1225– 1226, AD 129:910–911, 1993 Periodic fever BJD 151:99–104, 2004 Sarcoid – Heerfordt’s syndrome – uveoparotid fever; parotid gland enlargement, uveitis, fever, cranial nerve palsies (facial nerve) JAAD 13:314, 1985

METABOLIC DISEASES Gout – podagra or polyarticular gout Paroxysmal nocturnal hemoglobinuria – petechiae, ecchymoses, hemorrhagic bullae; ulcers; red plaques which become hemorrhagic bullae with necrosis; lesions occur on legs, abdomen, chest, nose, and ears; fever; deficiency of enzymes – decay-accelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL) AD 148:660– 662, 2012; AD 138:831–836, 2002; AD 122:1325–1330, 1986; AD 114:560–563, 1978

NEOPLASTIC DISORDERS Angioimmunoblastic T-cell lymphoma Medicine (Balt)98:e16932, 2019; Clin J Gastroenterol 11:302–308, 2018; NEJM 361:900–911, 2009 Hydroa vacciniforme-like Epstein-Barr virus-associated lymphoproliferative disease – edema of cheeks, eyelids, ears, and lips Ped Derm 29:96–100, 2012

Behcet's disease JAAD 41:540–545, 1999; JAAD 40:1–18, 1999; NEJM 341:1284–1290, 1999; JAAD 36:689–696, 1997; Ped Derm 11:95–101, 1994 Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; translucent skin-colored papules (non-caseating granulomas) of trunk and extremities with uveitis, synovitis, symmetric polyarthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints); uveitis, iritis, vitritis, closed-angle glaucoma; mutations in NOD2 (nucleotide-binding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) JAAD 68:834– 853, 2013; AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996; chromosome 16p12-q21 JAAD 49:299–302, 2003; Am J Hum Genet 76:217–221, 1998; Am J Hum Genet 59:1097–1107, 1996 CANDLE syndrome (chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperature) – autosomal recessive; annular violaceous plaques, fevers, edematous eyelids, progressive facial lipodystrophy, arthralgia, delayed physical development JAAD 68:834–853, 2013 Familial hemophagocytic lymphohistiocytosis – macules and papules with fever Familial Mediterranean fever – fever for 6–72 hours; monoarticular arthritis, severe abdominal pain, pleurisy, leukocytoclastic vasculitis resembling HSP and polyarteritis nodosa, scrotal pain and edema, AA amyloid JAAD 68:834–853, 2013; AD 144:392–402, 2008; Medicine 77:268–297, 1998; AD 134:929–931, 1998; QJMed 75:607–616, 1990; autosomal recessive; erysipelas-like erythema – mutation in MEFV/pyrin/marenostrin JAAD 68:834–853, 2013; JAAD 42:791–795, 2000; AD 136:1487–1494, 2000; mimicking infectious cellulitis; annular recurrent plaque of buttocks Clin Inf Dis 58:1273– 1338, 2014; Ann Int Med 142:47–55, 2005; NEJM 350:904–912, 2004; Isr Med Assoc J 1:31–36, 1999; Q J Med 75:607–616, 1990; red patch with pale areas AD 143:1080–1081, 2007 Hyper IgD syndrome – autosomal recessive; morbilliform eruptions, red macules or papules, urticaria, red nodules, urticaria, combinations of recurrent periodic fever, no arthritis, rather arthralgias, and

Fever, Arthritis, and Exanthem rash, annular erythema, and pustules, abdominal pain with vomiting and diarrhea, oral and vaginal aphthae; splenomegaly, cervical lymphadenopathy; elevated IgD and IgA – mevalonate kinase deficiency (MVK); seen in Dutch JAAD 68:834–853, 2013; AD 144:392–402, 2008; Ped Derm 22:138–141, 2005; AD 136:1487– 1494, 2000; AD 130:59–65, 1994; Medicine 73:133–144, 1994; Lancet 1:1084–1090, 1984 IgG4-related disease – inflammatory multiorgan fibrotic disease NEJM 373:1762–1772, 2015 Kawasaki's disease JAAD 69:501–510, 2013 Kikuchi’s disease – red macules, malar erythema, oral ulcers, photosensitivity, conjunctival injection, lymphadenopathy, fever, arthralgia JAAD 59:130–136, 2008; morbilliform eruption Ped Derm 24:459–460, 2007 Muckle-Wells syndrome – autosomal dominant; macular erythema (evanescent red macules), urticaria (cold air urticaria) lesions lasting 1–2 days, deafness, extremity pain, arthralgias of knees and ankles with arthritis; progressive sensorineural hearing loss; nephropathy, AA amyloidosis with neuropathy; fever and rash more severe in evening; mutation in gene encoding CIAS, NALP3 (cryopyrin) JAAD 68:834–853, 2013; AD 144:392–402, 2008; AD 142:1591–1597, 2006; BJD 151:99–104, 2004; JAAD 39:290–291, 1998; BJD 100:87–92, 1979; QJMed 31:235–248, 1962 NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic self-limiting fever, polyarthritis, polyarthralgia, red plaques of face and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – cryopyrinopathy with mutation in CIAS1 (encodes cryopyrin); edematous papules and plaques, urticarial-like lesions in newborn, lesions, chronic aseptic meningitis, arthralgias of knees and ankles with disabling deforming arthropathy with epiphyseal bone formation (osseous overgrowth), deafness, hepatosplenomegaly, anterior uveitis, vitreitis, papilledema, corneal stromal keratopathy; blindness, mental retardation; high frequency hearing loss, developmental delay; recurrent fever and rash more severe in evening; headache, macrocephaly, cerebral atrophy; mutation in NALP3 (CIAS 1) which encodes cryopyrin JAAD 68:834–853, 2013; AD 144:392–402, 2008; AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319–321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005; PAPA syndrome (familial recurrent arthritis) – autosomal dominant; cystic acne, sterile abscesses, cutaneous ulcers including pyoderma gangrenosum, sterile pyogenic destructive arthritis; CD2-binding protein (CD2BP1) JAAD 68:834–853, 2013; AD 144:392–402, 2008 PAPASH syndrome SAPHO syndrome - palmoplantar pustulosis with sternoclavicular hyperostosis; acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis Cutis 71:63–67, 2003; Cutis 64:253–258, 1999; Cutis 62:75–76, 1998; Rev Rheum Mal Osteoarthritic 54:187–196, 1987; Clin Rheumatol 5:118–123, 1986; Ann Rev Rheum Dis 40:547–553, 1981 Schnitzler's syndrome – chronic urticaria, intermittent fever, and IgM monoclonal gammopathy (macroglobulinemia), high ESR, leukocytosis, arthralgia, arthritis, with disabling bone pain (osteosclerotic) of distal femur and proximal tibia, palpable lymphadenopathy, hepatosplenomegaly JAAD 68:834–853, 2013; AD 143:1046–1050,

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2007; JAAD 56:S120–122, 2007; J Eur Acad Dermatol Venereol 16:267–270, 2007; BJD 142:954–959, 2000; JAAD 30:316–318, 1994; AD 130:1193–1198, 1994; JAAD 20:855–857, 1989; JAAD 20:206–211, 1989 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial Hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) – painful erythematous patches, tender red plaques, fever for 7–21 days, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, purpuric lesions resembling Henoch-Schonlein purpura; lesions resolving with ecchymoses, conjunctivitis, periorbital edema, localized myalgia which may be migratory resulting in muscle stiffness, arthralgia, abdominal pain, headache; Irish and Scottish predominance; upper extremities most commonly involved; skin lesions and myalgias move proximal to distal; renal and hepatic involvement; mutation in TNFRSF1A – gene encoding 55kDa TNF receptor JAAD 68:834–853, 2013; AD 144:392–402, 2008; AD 136:1487–1494, 2000

TOXINS Katayama’s disease – personal observation

TRAUMA Cold panniculitis - red patch of abdomen in febrile infant Ped Derm 29:658–659, 2012

VASCULAR LESIONS Cholesterol emboli Fat embolism syndrome – persistent somnolence, fever, tachycardia, respiratory symptoms, petechial eruption NEJM 375:370–378, 2016 Immune thrombocytopenic purpura MMWR 65:1–44, May 23, 2016 Polyarteritis nodosa NEJM 368:2220–2225, 2013; cutaneous polyarteritis nodosa – fever, muscle weakness and myalgia, and livedo with necrosis (livedo racemosa) BJD 171:201–202, 2014; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014 Vasculitis – leukocytoclastic vasculitis AD 134:309–315, 1998 Temporal arteritis (giant cell arteritis) Arthritis Rheum 42:1296, 1999; with scalp necrosis AD 143:1079–1080, 2007 Thrombotic thrombocytic purpura MMWR 65:1–44, May 23, 2016

FEVER, ARTHRITIS, AND EXANTHEM  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE REGULATION Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; translucent skin-colored papules (non-caseating granulomas) of trunk and extremities with uveitis, synovitis,

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symmetric polyarthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints); uveitis, iritis, vitritis, closed-angle glaucoma; mutations in NOD2 (nucleotide-binding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) JAAD 68:834– 853, 2013; AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996; chromosome 16p12-q21 JAAD 49:299–302, 2003; Am J Hum Genet 76:217–221, 1998; Am J Hum Genet 59:1097–1107, 1996 Collagen vascular diseases Common variable immunodeficiency BJD 144:597–600, 2001 Familial cold autoinflammatory syndrome (cold urticaria) – nonpruritic urticarial rash precipitated by cold; conjunctivitis, arthralgias of knees and ankles and arthritis; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin); CIAS1 Ped Derm 24:85–89, 2007; AD 142:1591–1597, 2006; JAAD 54:319– 321, 2006; BJD 150:1029–1031, 2004; JAMA 114:1067–1068, 1940 Hyper IgD syndrome – autosomal recessive; red macules or papules, urticaria, red nodules, combinations of periodic fever, arthritis, arthralgias, and rash, annular erythema, and pustules, abdominal pain with vomiting and diarrhea, lymphadenopathy; elevated IgD and IgA – mevalonate kinase deficiency Ped Derm 22:138–141, 2005; AD 136:1487–1494, 2000; AD 130:59–65, 1994; Medicine 73:133–144, 1994; Lancet 1:1084–1090, 1984 Juvenile rheumatoid arthritis (Still's disease) Med Chir Trans 80:47, 1897 Serum sickness NEJM 311:1407–1413, 1984; Dermatol Clin 3:107–117, 1985; associated with hepatitis B Arch Int Med 141:623–629, 1981 Systemic-onset juvenile idiopathic arthritis – spiking fevers, daily evanescent morbilliform eruption, polyarticular arthritis JAAD 68:834–853, 2013

 Togavirus – morbilliform, maculopapular-petechial (Sindbis BJD 135:320–323, 1996; BJD 80:67–74, 1968; chikungunya Trans R Soc Trop Med Hyg 49:28–32, 1955; and O’Nyong-Nyong fever Trans R Soc Med Hyg 55:361–373, 1961; bunyavirus fevers) with joint pains Barmah Forest virus – similar to Ross River virus Med J Aust 152:463–466, 1990 Capnocytophagia canimorsus Eur J Epidemiol 12:521–533, 1996 Chikungunya fever NEJM 372:1657–1664, 2015; JAMADerm 151:257–258, 2015; JAAD 58:308–316, 2008; Clin Inf Dis 20:225– 231, 1995; JAAD 58:308–316, 2008; Clin Inf Dis 20:225–231, 1995  Fever, flush of face and upper chest, chills, severe pain in large joints  Morbilliform eruption of the trunk, extensor surfaces with islands of sparing; burning pinnae, severe conjunctival injection   East Africa, India Coccidioidomycosis Coxsackie virus A6 (atypical hand, foot, and mouth disease) – red papulovesicles of fingers, palmar erythema, red papules of ears, red papules of antecubital fossa, perioral papulovesicles, vesicles of posterior pharynx; crusted papules of scalp, ears, and face; purpuric targetoid painful vesicular lesions of hands and feet, arthritis, fissured scrotum JAMA Derm 149:1419–1421, 2013; JAAD 69:736–741, 2013 Dengue fever (flavivirus) – in first 24 hours, flushing of face, neck, and chest; morbilliform or scarlatiniform eruption with islands of sparing on day 3–4, then becomes petechial; classic dengue fever with joint and bone pain (breakbone fever) with severe backache JAAD 58:308–316, 2008; JAAD 49:979–1000, 2003; JAAD 46:430–433, 2002; Bull Soc Pathol Exot 86:7–11, 1993 Echovirus

DRUG REACTIONS Azathioprine hypersensitivity syndrome – fever, chills, erythema nodosum, Sweet’s syndrome, leukocytoclastic vasculitis, pustular drug eruption, urticarial, purpuric eruption, leukocytosis, nausea, vomiting, diarrhea JAAD 65:184–191, 2011 Drug hypersensitivity, multiple drugs; DRESS

INFECTIONS AND INFESTATIONS Acute bacterial endocarditis Adenovirus infection African tick bite fever (Rickettsia africae) – hemorrhagic pustule, purpuric papules; transmitted by Amblyomma ticks) – high fever, arthralgia, myalgia, fatigue, rash in 2–3 days, with eschar, maculopapules, vesicles, and pustules JAAD 48:S18–19, 2003 Arbovirus fever Dengue fever   West Nile virus JAAD 51:820–823, 2004  O'nyong-Nyong fever – morbilliform eruption, fever, arthritis; sub-Saharan Africa  Sindbis – fever, rash, arthritis; Europe, Asia, Africa, Australia  Ross river fever (togavirus) – fatigue, arthralgia, arthritis, morbilliform eruption of trunk, palms and soles, face, and scalp JAAD 58:308–316, 2008; Clin Rheum Dis 12:369–388, 1986 Oropouche fever Phlebotomus fever   Mayaro fever Mayaro – Brazil and Trinidad

Erysipeloid Epstein-Barr virus Gonococcemia Am Fam Phys 34:77–79, 1986   Acral purpuric vesicles, pustules   Gray necrotic centers   Hemorrhagic bullae   Mean number of lesions is 10–16   Skin lesions resolve in 3–5 days  Polyarticular arthritis, especially wrist, ankle, extensor tendon sheaths, tenosynovitis   Monoarticular arthritis   Women during or after menses Helicobacter cinaedi – cellulitis and monoarticular arthritis Clin Inf Dis 20:564–570, 1995 Hepatitis A JAAD 37:659–661, 1997 Hepatitis B JAAD 8:539–548, 1983   Urticaria – “yellow hives”   Maculopapular eruption   Angioneurotic edema   Nonthrombocytopenic petechiae  Pruritus   Serum sickness – reticulated fine red blanching erythema   Acute migratory or additive polyarthritis   Arthritis subsides with onset of jaundice HHV-6 reactivation in chronic graft vs. host disease – morbilliform eruption, fever, diarrhea JAAD 72:696–702, 2015 HIV-1 acute infection – erythematous macules, morbilliform eruptions on trunk and face, also palms and soles with arthralgias JAAD 28:167–173, 1993; AD 134:1279–1284, 1998

Fever, Arthritis, and Exanthem Human bite Human herpesvirus 8 – relapsing inflammatory syndrome; fever, lymphadenopathy, splenomegaly, edema, arthrosynovitis, exanthem of hands, wrists, and elbows NEJM 353:156–163, 2005 Infectious mononucleosis Jarisch-Herxherimer reaction – treatment of syphilis, onchocerciasis, Lyme disease, strongyloidiasis AD 125:77–81, 1989; Hautarzt 35:588–590, 1984 Lassa fever (arenavirus) – morbilliform or petechial rash with conjunctivitis J Infect Dis 155:445–455, 1985 Leprosy – erythema nodosum leprosum (vasculitis) – painful facial nodules with fever, arthralgias, dactylitis, iritis, uveitis, orchitis, adenitis, glomerulonephritis, tibial periostitis; ulcerated nodules JAAD 83:17–30, 2020; JAAD 51:416–426, 2004; AD 138:1607–1612, 2002 Lyme disease Clin Inf Dis 31:533–542, 2000   Erythema migrans (erythema chronicum migrans)   Tick bite, red papule 3–32 days later, ECM   Thigh, groin, axilla   Bright red outer borders, flat, raised   Central clearing, indurated, vesicular, bullous, necrotic   Secondary lesions   Multiple annular, smaller, migrate less   Lack indurated centers   Recurrent skin lesions  Borrelial lymphocytoma (blue-red nodule of earlobe, scrotum, breast)   Acrodermatitis chronica atrophicans  Arthritis   Late manifestation, from several weeks to years later   Intermittent, recurring in up to 40% of untreated patients Lymphogranuloma venereum JAAD 41:511–529, 1999 Mayaro virus – arbovirus; fever, headache, myalgia, arthralgia; exanthema of trunk and extremities; Brazil and Trinidad JAAD 58:308–316, 2008 Melioidosis – Burkholderia pseudomallei; septic arthritis, abscesses, ulcers Clin Inf Dis 31:981–986, 2000 Meningococcemia Ped Derm 13:483–487, 1996; chronic – fever and arthralgias Clin Exp Rheumatol 20:553–554, 2002; BJD 153:669– 671, 2005; Med J Aust 153:556–559, 1990 Moraxella osloensis – gonococcemia-like infection Cutis 21:657– 659, 1978 Mumps – adult males Murine typhus (Rickettsia typhi) – arthralgia MMWR 52:1224–1226, 2003 Ockelbo disease – arthritis, exanthem – due to Dindbis-virus like agent Lancet Apr3;1(8275);795–796, 1982 O’Nyong-Nyong fever –fever, arthritis, lymphadenopathy; exanthem of face, trunk, extremities, especially the neck, back, inner thighs, and arms JAAD 58:308–316, 2008 Parvovirus B19 (erythema infectiosum, fifth disease) JAAD 27:466, 1992; J Clin Inf Dis 21:1424–1430, 1995   Adults seldom have typical "slapped cheeks"  Papular-purpuric glove and socks syndrome Ped Derm 15:413, 1998   Macular, lacy or reticulate erythema on the extremities  Bullous papular-purpuric gloves and socks syndrome with oral aphthae of tongue JAAD 60:691–695, 2009  Pruritus, sometimes severe, with or without rash in a patient with acute onset arthritis   Sudden onset, symmetric polyarthritis, particularly of hands   Lupus-like presentation J Rheumatol 19:169–171, 1992

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Pasteurella multocida – periocular abscess and cellulitis; tenosynovitis, septic arthritis Am J Ophthalmol 128:514–515, 1999; JAAD 33:1019–1029, 1995 Pogost disease – alphavirus infection with rash and arthritis J Clin Lab Immunol 21:77–82, 1986 Rat bite fever (Streptococcus moniliformis) – fever, arthritis, exanthem; papules and papulopustules of face and hand; hand and foot swellings Clin Inf Dis 60:1388, 1436–1437, 2015; Ped Derm 29:767–768, 2012; acral hemorrhagic pustules JAAD 38:330–332, 1998; septic arthritis; arthralgias AD 148:1411–1416, 2012; Clin Infect Dis 43:1586–1587, 1616–1617, 2006; MMWR 53:1198–1202, 2005; Clin Orthop 380:173–176, 2000   Erythematous macules, papules 2–3 days after symptoms:    most marked on the extremities, particularly about joints;    measles-like, involves palms and soles   Fever, chills, headache, myalgias, arthritis after rat bite   healed  Haverhill fever – erythema arthriticum epidemicum ("Sodoku") – Spirillium minus Relapsing fever (tick-borne relapsing fever) – Ornithodoros soft ticks transmitting Borrelia hermsii, B.turicata, or B. parkeri; 1–2 cm rose-­colored macules, papules, petechiae, purpura, facial flushing; arthralgias, iritis, myalgia JAAD 49:363–392, 2003; diffuse macular rash Rheumatic fever NEJM 369:75–80, 2013; JAAD 8:724–728, 1983 Rickettsia parkeri rickettsiosis – Gulf coast tick (Amblomma maculatum); eschar with surrounding petechiae, fever, fatigue, headache, myalgia, arthralgia, morbilliform or vesiculopapular rash of trunk and extremities, palms and soles, and occasionally the face; some lesions with small vesicle or pustule Clin Inf Dis 47:1188– 1196, 2008 Rocky Mountain spotted fever Roseola – adults Rubella NEJM 369:558, 2013 Rubella vaccination Scarlet fever with septic arthritis – Streptococcus pyogenes; scarlatiniform (sandpaper) rash JAAD 39:383–398, 1998; JAAD 21:891–903, 1989 Scedosporium apiopermum – septic arthritis; periarticular erythema Clin Inf Dis 56:1778, 1838–1839, 2013 Schistosomiasis – Katayama fever Scrub typhus – Orientia tsutsugamushi; Asia; trombiculid mites NEJM 373:2455, 2015 Subacute bacterial endocarditis  Petechiae   Splinter hemorrhages, proximal   Cryoglobulins causing purpura   Vasculitis causing palpable purpura   Osler's node   painful erythematous nodule with a pale center; suddenly appears, usually on the fingertips; persists for hours to days   Janeway lesion    hemorrhagic and non-tender; may be nodular and commonly    occurs on the palms and soles JAAD 22:1088–1090, 1990 Syphilis – secondary Infect Dis Clin North Amer 1:83–85, 1987; congenital – osteochondritis – tibia and fibula at birth; later see osteomyelitis syphilitica (syphilitic dactylitis); Clutton’s joint – painless synovitis of the knees; sabre shins; Higoumenakis’ sign – sternoclavicular swelling in congenital syphilis; malignant lues Int J STDs and AIDS 23:599, 2012; Sex Trans Dis 36:512– 514, 2009

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Tick-borne relapsing fever – Ornithodoros (soft tick); Borrelia genus; high fever in irregular pattern, chills, headache, myalgia, arthralgia, fatigue, macular rash, conjunctival injection, hepatosplenomegaly, epistaxis, meningeal signs Cutis 82:38–46, 2008; Pediatr Drugs 7:163–176, 2005 Trench fever – red macules, 1cm or less; fever, malaise, chills, conjunctivitis, myalgias, arthralgias Clinics in Dermatol 28:483–488, 2010 Varicella – 1–5 large joints, may last up to 3 years J Clin Pathol 45:267–269, 1992 Zika virus – fever, morbilliform (macular and papular exanthem), arthralgia, conjunctivitis, myalgia, headache, retro-orbital pain, edema; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) MMWR 65:1161–1165, 2016; NEJM 360:2536–2543, 2009

INFLAMMATORY DISORDERS Erythema nodosum Ann Rheum Dis 19:174–180, 1960; Lofgren’s syndrome – erythema nodosum with sarcoidosis and arthralgias Ped Derm 22:366–368, 2005 Neutrophilic urticaria (neutrophilic urticaria with systemic inflammation) – urticaria, night sweats, fever, polyarticular arthritis; increased IL-1; treated with anakinra AD 149:453–458, 2013 Periodic fever BJD 151:99–104, 2004 Sarcoid – Lofgren’s syndrome; erythema nodosum, hilar adenopathy, fever, migrating polyarthritis, acute iritis

METABOLIC DISORDERS Pancreatic panniculitis – periarticular subcutaneous nodules JAAD 45:325–361, 2001; JAAD 34:362–364, 1996; J Rheumatol 19:630– 632, 1992; Arthritis Rheum 22:547–553, 1979

PRIMARY CUTANEOUS DISORDERS Acne fulminans JAAD 28:572–579, 1993; Clin Rheumatol 5:118– 123, 1986 Febrile ulceronecrotic Mucha- Habermann disease (pityriasis lichenoides et varioliformis acuta) J Rheumatol 16:387–389, 1989; crusted ulcerated red plaques; diarrhea, pulmonary involvement, abdominal pain, CNS symptoms, arthritis Ped Derm 29:53–58, 2012

SYNDROMES CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of lateral forehead, gynecomastia, wide spaced nipples, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, splenomegaly, protuberant abdomen BJD 170:215–217, 2014; JAAD 68:834–853, 2013; Ped Derm 28:538–541, 2011; JAAD 62:487–495, 2010 Cryopyrin-associated periodic syndrome (CAPS) – urticarial-like eruptions, fever, distal arthralgia, neurologic symptoms, eye disease, amyloidosis JAAD 68:834–853, 2013

Hemophagocytic lymphohistiocytosis syndrome – fever, pancytopenia, lymphadenopathy, hepatomegaly, splenomegaly, neurologic, joint, purpura, morbilliform eruption, kidney, and cardiac involvement, central nervous system dysfunction Eur Rev Med Pharmacol Sci, 16:1414–1424, 2012; Genes Immunol 13:289–298, 2012   Familial HLH – known genetic defects (perforin)   Immune deficiencies   Chediak-Higash syndrome   Griscelli syndrome    X-linked lymphoproliferative syndrome   Acquired   Infections   Endogenous products   Rheumatic diseases   Neoplasms Familial Mediterranean fever – monoarthritis in 75% Medicine 77:268–297, 1998; AD 134:929–931, 1998; QJMed 75:607–616, 1990; autosomal recessive; erysipelas-like erythema – mutation in pyrin/marenostrin JAAD 42:791–795, 2000; AD 136:1487–1494, 2000 Kawasaki’s disease – arthralgias, especially in adults JAAD 69:501–510, 2013 Kikuchi’s disease – red macules, malar erythema, oral ulcers, photosensitivity, conjunctival injection, lymphadenopathy, fever, arthralgia JAAD 59:130–136, 2008; morbilliform eruption Ped Derm 24:459–460, 2007 Majeed syndrome – autosomal recessive; chronic recurrent multifocal osteomyelitis; congenital dyserythropoietic anemia, periodic fevers; Sweet’s syndrome; chronic pustulosis; mutation in LPIN2 J Clin Immunol 28(Suppl 1)S73–83, 2008; J Med Genet 4:551–557, 2005; Eur J Pediatr 160:705–710, 2001 Muckle-Wells syndrome – autosomal dominant; macular erythema (evanescent red macules), urticaria (cold air urticaria), deafness, extremity pain, arthralgias of knees and ankles with arthritis; nephropathy, AA amyloidosis with neuropathy; fever and rash more severe in evening; mutation in gene encoding NALP3 (cryopyrin) SkinMed 11:80–83, 2013; AD 142:1591–1597, 2006; BJD 151:99– 104, 2004; JAAD 39:290–291, 1998; BJD 100:87–92, 1979; QJMed 31:235–248, 1962 NOD 2 mutations (nucleotide-binding oligomerization domain 2 – dermatitis, weight loss with gastrointestinal symptoms, episodic self-limiting fever, polyarthritis, polyarthralgia, red plaques of face and forehead, urticarial plaques of legs, patchy erythema of chest, pink macules of arms and back JAAD 68:624–631, 2013 NOMID – (neonatal onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – urticarial lesions, chronic meningitis, arthralgias of knees and ankles with deforming arthropathy with epiphyseal bone formation, deafness, hepatosplenomegaly, uveitis, vitreitis, papilledema, corneal stromal keratopathy; mental retardation; fever and rash more severe in evening; mutation in NLRP3 (CIAS 1) which encodes cryopyrin AD 144:392–402, 2008; AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319– 321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005 PAPA (pyogenic arthritis with pyoderma gangrenosum) syndrome – pyoderma gangrenosum, cystic acne, acne fulminans, non-axial destructive aseptic arthritis; sterile abscesses at injection sites; attacks last 5 days; mutation in CD2 binding protein-1 Ped Derm 22:262–265, 2005; Proc Natl Acad Sci USA 100:13501–13506, 2003; Mayo Clin Proc 72:611–615, 1997

Fibromatoses in Children

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PAPASH syndrome

CONGENITAL AND JUVENILE

SAPHO syndrome – palmoplantar pustulosis with sternoclavicular hyperostosis; acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis Cutis 71:63–67, 2003; Cutis 64:253–258, 1999; Cutis 62:75–76, 1998; Ann Rheum Dis 56:52–58, 1997: AD 128:699–700, 1992; JAAD 18:666–671, 1988;

Fibrous tumors of infants   Calcifying aponeurotic fibroma   Digital fibromatosis   Fibromatosis colli   Fibrous hamartoma of infancy   Hyaline fibromatosis Ped Derm 6:68–75, 1987  Infantile myofibromatosis Dermatol Online J Oct 16, 2015; JAAD 71:264–270, 2014; AD 134:625–630, 1998   Intravascular fasciitis

Rev Rheum Mal Osteoarthritic 54:187–196, 1987; Clin Rheumatol 5:118–123, 1986; Ann Rev Rheum Dis 40:547–553, 1981 Sweet's syndrome JAAD 23:494–498, 1990; Arthritis Rheum 18:35–41, 1975; BJD 76:349–356, 1964; including drug-induced Sweet’s syndrome – red plaques, nasal ulcers, perianal ulcers – celecoxib, G-CSF, all-trans retinoic acid JAAD 45:300–302, 2001; Sweet’s syndrome in children – arthritis, arthralgia, tibial pain, osteomyelitis Ped Derm 26:452–457, 2009; drug-induced JAAD 34:918–923, 1996 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) – erythematous patches, tender red plaques, fever, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, lesions resolving with ecchymoses, conjunctivitis, periorbital edema, myalgia, arthralgia with limitation of joint movement, abdominal pain, headache; Irish and Scottish predominance; mutation in TNFRSF1A – gene encoding 55 kDa TNF receptor AD 136:1487–1494, 2000; Mayo Clin Proc 72:806–817, 1997

TRAUMA Cold panniculitis – red patch of abdomen in febrile infant Ped Derm 29:658–659, 2012

Congenital generalized fibromatosis Congenital multiple fibromatosis Infantile digital fibromatosis – skin-colored papule or nodule on dorsal or lateral aspect of digits at birth Ped Derm 25:72–75, 2008; JAAD 49:974–975, 2003 Primitive myxoid mesenchymal tumor of infancy F1000 Faculty Review Dec 20, 2018

SOLITARY LESIONS Aggressive infantile fibromatosis Calcifying aponeurotic fibroma Congenital solitary fibromatosis Dermatofibrosarcoma protuberans – in infants and children J Cutan Pathol 18:241–246, 1991 Diffuse infantile fibromatosis Digital fibromatosis (recurrent infantile digital fibromatosis) Fibromatosis colli Fibrous hamartoma of infancy Infantile desmoid-type fibromatosis

VASCULAR LESIONS

Juvenile hyaline fibromatosis Ped Derm 6:68–75, 1989

Cholesterol emboli

Infantile myofibromatosis/lipofibromatosis – solitary myofibroma or congenital multicentric fibromatosisis; congenital generalized fibromatosis with visceral involvement

Fat embolism syndrome – persistent somnolence, fever, tachycardia, respiratory symptoms, petechial eruption NEJM 375:370–378, 2016 Polyarteritis nodosa NEJM 368:2220–2225, 2013; cutaneous polyarteritis nodosa – fever, muscle weakness and myalgia; livedo with necrosis (livedo racemosa) BJD 171:201–202, 2014; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in CECR1 (adenosine deaminase) NEJM 370:921–931, 2014

Infantile digital fibromatosis Ped Derm 8:137–139, 1991 Intravascular fasciitis

JUVENILE AND ADULT Abdominal and extra-abdominal desmoid Aggressive polyfibromatosis Australas J Dermatol 37:205–207, 1996

Vasculitis – leukocytoclastic AD 134:309–315, 1998

Aponeurotic fibromatosis Dermatol Surg 33:1380–1383, 2007; calcified scalp

Temporal arteritis (giant cell arteritis) Arthritis Rheum 42:1296, 1999; with scalp necrosis AD 143:1079–1080, 2007

Atypical cutaneous fibrous histiocytoma Am J Dermatopathol 8:467–471, 1986

Thrombotic thrombocytopenic purpura MMWR 651–44, May 23, 2016

Atypical fibroxanthoma Cancer 15:368–376, 1986; Cutis 51:47–48, 1993 Atypical polypoid dermatofibroma JAAD 24:561–565, 1991

FIBROMATOSES IN CHILDREN

Buschke-Ollendorff syndrome – dermatofibrosis lenticularis disseminata AD 118:44–46, 1982

AD 138:1245–1250, 2002; Ped Derm 8:306–309, 1991; AD 122:89–94, 1986; JAAD 10:365–371, 1984

Clear cell sarcoma Clinics in Dermatol 35:85–98, 2017

428 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Cowden’s disease – multiple sclerotic fibromas of the skin J Cutan Pathol 19:346–351, 1992

Lupus erythematosus – subacute cutaneous lupus erythematosus; neonatal lupus

Dermal pleomorphic liposarcoma J Cut Pathol 40:734–739, 2013

Still’s disease – adult onset Still’s disease – erythema chronicum migrans-like lesions J Eur Acad Dermatol Venereol 19:360–363, 2005

Dermatofibrosarcoma protuberans Dermatomyofibroma J Cutan Pathol 19:85–93, 1992 Desmoplastic fibroblastoma J Cutan Pathol 25:450–454, 1998 Desmoplastic melanoma AD 111:753–754, 1975 Epithelioid sarcoma Clinics in Dermatol 35:85–98, 2017 Fibromyxoma, superficial acral (cellular digital fibroma) Rev Ortop (Sao Paolo) 54:491–496, 2019; Am J Dermatopathol 39:849–852, 2017; J Cutan Pathol 7:335–341, 1980 Hyaline fibromatosis, juvenile and infantile systemic hyalinosis (hyaline fibromatosis syndrome) Am J Dermatopathol 38:e60–63, 2016 Solitary cutaneous myofibromas J Cutan Pathol 23:437–444, 1996 Myxoid fibroblastoma Am J Dermatopathol 14:536–541, 1992 Myxoinflammatory fibroblastic sarcoma Clinics in Dermatol 35:85–98, 2017 Palmo-plantar fibromatosis (Dupuytren's contracture) (Ledderhose disease) Penile (Peyronie's disease) Pleomorphic fibroma, subungual Dermatol Online J Nov 15, 2016 Pleomorphic sclerotic fibroma – trunk or proximal extremities; papule, nodule; asymptomatic tumor with slow growth 4–40 mm; Dermatology 198:69–72, 1999

INFECTIONS AND INFESTATIONS Erythema chronicum migrans of Lyme disease Erythema marginatum of rheumatic fever Leprosy – macular lepromatous AD 113:1027–1032, 1997 Tinea corporis – An Bras Dermatol 93:141–142, 2018; tinea incognito Med Mycol Case Rep 18:8–11, 2017 Tinea imbricata

INFLAMMATORY DISORDERS Neutrophilic figurate erythema of infancy Am J Dermatopathol 19:403–406, 1997

NEOPLASTIC DISORDERS Lymphoma – angioimmunoblastic T-cell lymphoma BJD 177:e75, 2017; cutaneous T-cell lymphoma JAAD Case Rep 22:288–290, 2017; diffuse large cell B-cell lymphoma JAAD Case Rep 5:475– 477, 2019; panniculitis-­like B cell lymphoma

Cutaneous sclerotic fibroma Am J Dermatopathol 21:571–574, 1999

PRIMARY CUTANEOUS DISEASES

FIBROUS TUMORS, DIFFERENTIAL DIAGNOSIS

Annular erythema of infancy JAMADerm 154:113–1214, 2018; Ped Derm 10:46–48, 1993

Dermatofibroma

Erythema annulare centrifugum – large number of causes; separate listing Arch Int Med 144:2090–2092, 1984

Dermatomyofibroma – 1–2 cm red brown plaques or nodules of neck, arms, upper trunk Dermatofibrosarcoma protuberans – blue-red nodule or multilobulated tumor of trunk or proximal extremities

Eosinophilic annular erythema An Bras Dermatol 92(suppl 1)65–68, 2017; AD 150:895–896, 2014

Erythema gyratum repens-like psoriasis Int J Derm 39:695–697, 2000 Erythema papulatum centrifugum Australas J Dermatol Nov 6, 2019

Desmoid-type fibromatosis – deep seated nodule of head, neck, extremities, trunk

Erythrokeratoderma variabilis Indian Dermatol Online J 4:340–343, 2013

Fibrous hamartoma of infancy – 2–5 cm nodule of axilla, shoulders, upper chest

Familial annular erythema Ped Derm 28:56–58, 2011

Giant cell fibroblastoma – skin colored nodule or subcutaneous nodules of back or legs

Neutrophilic figurate erythema Am J Dermatopathol 39:344–350, 2017

Infantile digital fibromatosis – pink nodule of dorsal digit Infantile myofibroma or myofibromatosis – skin-colored to vascular-­ appearing rubbery nodules of head, neck, trunk, and arms Plaque-like myofibroblastic tumor – red to violaceous plaque of back; ulcerated plaque Ped Derm 30:600–607, 2013

FIGURATE ERYTHEMAS  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Bullous pemphigoid – urticarial, non-bullous Clin Exp Derm 24:446–448, 1999; BJD 117:385–388, 1987; Clin Exp Derm 7:401–406, 1982

Keratolytic winter erythema Pityriasis rubra pilaris Pseudoglucagonoma syndrome with celiac disease, Crohn’s disease, chronic pancreatitis, hepatic cirrhosis An Bras Dermato 88:9–22, 2013 Psoriasis Int J Dermatol 39:695–697, 2000

PARANEOPLASTIC DISORDERS Erythema gyratum repens Clin Exp Dermatol 26:510–512, 2001; Cutis 34:351–353, 355, 1984 Glucagonoma syndrome (necrolytic migratory erythema (glucagonoma syndrome) JAAD 54:745–762, 2006; Int J Dermatol 57:642–645, 2018 Infantile epidermodysplastic erythema gyratum AD 120:1601–1603, 1984

Fingertip Lesions

SYNDROMES

EXOGENOUS AGENTS

Hereditary angioedema – prodrome of non-pruritic serpiginous eruption (erythema marginatum-like); other prodromes include tingling fatigue, asthenia, and discomfort NEJM 382:1136–1148, 2020

Foreign body granuloma – digital papule; cactus spine (Opuntia cactus) granulomas Cutis 65:290–292, 2000; sea urchin granulomas

429

Inhalant abuse – frostbite; orofacial bullae, finger bullae

FINGERTIP LESIONS

INFECTIONS

 UTOIMMUNE DISORDERS OR DISEASES A OF IMMUNE DYSFUNCTION

Acute bacterial endocarditis

Allergic contact dermatitis – occupational (chromate), medications, latex, tulip or garlic fingers (hyperkeratotic dermatitis with fissures and subungual hyperkeratosis) Cutis 67:328–330, 2001; vesicular fingertip dermatitis from food proteins in milkers, veterinarians Contact Dermatitis 6:27–29, 1980, slaughterhouse workers Contact Dermatitis 21:221–224, 1989; chefs and sandwich makers Contact Dermatitis 2:28–42, 1976s; acrylic fingernails (“tips”); methyl methacrylate allergic contact dermatitis in dentist – fingertip purpura JAMADerm 150:784–785, 2014

Bacillary angiomatosis

Chronic granulomatous disease – chilblains JAAD 36:899–907, 1997; X-linked chronic granulomatous disease – photosensitivity, chilblain lupus of fingertips and toes Ped Derm 3:376–379, 1986

Erysipeloid – Erysipelothrix insidiosa (rhusiopathiae) – seal finger, blubber finger AD 130:1311–1316, 1994; Clin Microbiol Rev 2:354–359, 1989; JAAD 9:116–123, 1983

Dermatomyositis

Felon Hand Clin 14:547–555, 1998

Lupus erythematosus – systemic, discoid; chilblain lupus – fingers, toes, elbows, knees, calves, knuckles, nose, ears BJD 143:1050– 1054, 2000; Lupus 6:122–131, 1997; BJD 98:497–506, 1978; with anti-phospholipid antibodies Ped Derm 16:273–276, 1999; lupus vasculitis – personal observation

Fusarium solani – digital cellulitis

Rheumatoid vasculitis JAAD 17:355–359, 1987; rheumatoid neutrophilic dermatosis Cutis 78:133–136, 2006

Leishmaniasis – personal observation

Scleroderma (progressive systemic sclerosis) – CREST syndrome; acral pits; swollen fingertip with round fingerpad sign NEJM 381:1663, 2019; JAAD 24:67–69, 1991

CONGENITAL LESIONS Congenital ectopic nail – cutaneous horn of fingertip Ped Derm 30:267–269, 2013; congenital palmar nail syndrome, Pierre-Robin syndrome, ectodermal dysplasia, polydactyly, congenital onychodysplasia Congenital insensitivity to pain Cutis 513:373–374, 1993

Aspergillus fumigatus sepsis – personal observation Blistering distal dactylitis JAAD 17:310–311, 1987 Cat scratch disease, inoculation papule Ped Derm 5:1–9, 1988; multiple leg papules Cutis 49:318–320, 1992 Endocarditis – subacute bacterial endocarditis; Osler’s nodes (painful hemorrhagic bulla of thumb tip); extensive distal purpura with necrosis of legs; Janeway lesion – purpuric macule of sole; conjunctival hemorrhage JAMADerm 150:494–500, 2014

Gonococcemia Herpes simplex virus – paronychia (herpetic whitlow); chronic HSV of HIV disease; herpetic whitlow of toe tip Clin Inf Dis 40:579–580, 609–610, 2005 Lepromatous leprosy Milker's nodules JAAD 49:910–911, 2003 Orf – vascular nodule of fingertip JAMADerm 151:1032–1033, 2015; AD 126:235–240, 1990 Osler's node (subacute bacterial endocarditis) – small, red papules on distal finger and toe pads Clin Inf Dis 32:63, 149, 2001; NEJM 295:1500–1505, 1976 Osteomyelitis secondary to nail biting – fingertip swelling Ped Derm 7:189–90, 1990 Paronychia, acute or chronic Hand Clin 14:547–555, 1998 Rat bite fever Rocky Mountain spotted fever

DEGENERATIVE DISEASES Acquired subungual exostoses – papule JAAD 26:295–298, 1992 Carpal tunnel syndrome – chilblain-like lesions with necrosis

DRUGS Acral dysesthesia syndrome – capecitibine, cytarabine, fluorouracil, liposomal doxorubicin Am J Clin Dermatol 1:225–234, 2000 Doxycycline phototoxicity EGFR inhibitors – cut-like lesions BMJ Case Rep Aug 1, 2018 Sorafenib (multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of feet, hyperkeratotic plaque or blister of feet, red patches on pressure points, red swollen fingertips, gray blisters of fingerwebs, angular cheilitis, perianal dermatitis BJD 158:592–596, 2008

Septic emboli JAAD 47:S263–265, 2002 Sporotrichosis Syphilis – primary chancre; secondary Tularemia Tungiasis (Tunga penetrans) (toe-tip or subungual nodule) – crusted or ulcerated; callus-like lesion AD 144:1051–1056, 2008; Acta Dermatovenerol (Stockh)76:495, 1996; JAAD 20:941–944, 1989; AD 124:429–434, 1988 Varicella Plast Reconstr Surg 116:1578–1579, 2005 Verruca vulgaris Derm Surg 27:591–593, 2001

INFILTRATIVE LESIONS Amyloidosis – primary systemic amyloidosis associated with myeloma BJD 147:602, 2002

430 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Recurrent self-healing cutaneous mucinosis – red papules of palms and fingertips with pustules and vesicles BJD 143:650–652, 2000

INFLAMMATORY LESIONS Erythema multiforme Fibroblastic rheumatism – red tender swellings of toe tips JAAD 66:959–965, 2012 Interstitial granulomatous dermatitis – personal observation Pyoderma gangrenosum JAAD 16:141–142, 1987; JAAD 18:1084– 1088, 1988 Sarcoid – fingertip nodules JAAD 44:725–743, 2001; JAAD 11:713–723, 1984; on palmar aspects of fingers AD 132:459–464, 1996; lupus pernio JAAD 16:534–540, 1987; BJD 112:315–322, 1985

METABOLIC DISEASES Bullous dermatosis of hemodialysis JAAD 21:1049–1051, 1989 Calcinosis cutis – digital papules Cutis 66:465–467, 2000; CREST – acral pits; calcinosis cutis in children Cutis 66:465–467, 2000; dystrophic calcification AD 144:585–587, 2008; in Sjogren’s syndrome Lupus 19:762–764, 2010

blue, yellow, brown, skin-colored JAAD 47:429–435, 2002; Ped Derm 13:139–142, 1996; JAAD 37:523–549, 1997 Eccrine poromas – personal observation Enchondromas, subungual Derm Surg 27:591–593, 2001; J Bone Joint Surg Am 79:898–900, 1997 Epidermoid cyst Epithelioid sarcoma JAAD 14:893–898, 1986 Exostosis, subungual – hyperkeratotic subungual papule of fingertip Cutis 98:128–129, 2016; Derm Surg 27:591–593, 2001; JAAD 19:132, 1988 Fibroma, subungual Derm Surg 27:591–593, 2001; Fibrokeratoma, periungual – resembles accessory fingernail Cutis 35:451–454, 1985 Giant cell tumor of the tendon sheath – single or multiple BJD 147:403–405, 2002; JAAD 43:892, 2000; nodules of the fingers J Dermatol 23:290–292, 1996 Granular cell tumor – digital papule, paronychial nodule Cutis 35:355–356, 1985; Cutis 62:147–148, 1998 Kaposi’s sarcoma – digital papules JAAD 47:641–655, 2002 Keratoacanthoma – hyperkeratotic papule distal to hyponychium NEJM 367:2240, 2012

Cholesterol emboli – personal observation

Leukemia cutis – digital papule; preleukemic state of monocytosis and neutropenia – perniotic lesions BJD 81:327–332, 1969; chronic myelomonocytic leukemia – chilblain-like lesions BJD 115:607–609, 1986; AD 121:1048–1052, 1985; chronic myelomonocytic leukemia – chilblain-like lesions JAAD 50:S42–44, 2004; chronic lymphocytic leukemia – fingertip hypertrophy Cut Med Surg 7:57–60, 2003

Cryoglobulinemia

Lymphoma – CTCL

Erythropoietic porphyria – mutilation of fingertips

Melanocytic nevus

Gout, tophus – digital papule (s) Cutis 64:233–236, 1999; AD 134:499–504, 1998

Melanoma, subungual Derm Surg 27:591–593, 2001; amelanotic acral melanoma – red plaque of toe tip JAAD 69:700–707, 2013

Tyrosinemia type II – fingertip erosions Ped Derm 1:25–34, 1983 Xanthomas

Metastasis Hosp Med 59:819, 1998; bronchogenic carcinoma resembling felon J Hand Surg 8:325–328, 1983; squamous cell carcinoma of lung Rev Med Liege 54:65f3–654, 1999

NEOPLASTIC DISEASES

Myxoma of fingertip JAAD 22:343–345, 1990; embolic atrial myxoma – acral papule BJD 147:379–382, 2002

Calcium oxalate Am J Kid Dis 25:492–497, 1995; secondary oxalosis – papules on palmar skin of fingers JAAD 31:368–372, 1994; oxalate granuloma – fingertip papule JAAD 22:316–318, 1990

Acquired digital fibrokeratoma – digital papule AD 124:1559–1564, 1988; JAAD 12:816–821, 1985

Osteochondroma – personal observation

Acral calcified vascular leiomyoma – swollen fingertip JAAD 59:1000–1004, 2008

Osteosarcoma, subungual Derm Surg 27:591–593, 2001

Aggressive digital papillary adenocarcinoma – occur on fingers and toes Dermatol Surg 26:580–583, 2000; JAAD 23:331–334, 1990; aggressive digital papillary adenoma Cutis 69:179–182, 2002; AD 120:1612, 1984; exophytic friable multilobulated tumor JAAD 60:331–339, 2009 Atrial myxoma – acral red papules with claudication JAAD 32:881– 883, 1995; tender red fingertip papule Australas J Dermatol 56:218–220, 2015; BJD 147:379–382, 2002; JAAD 21:1080–1084, 1989 Chondroblastoma, subungual – toe tip Ped Derm 21:452–453, 2004 Clear cell syringofibroadenoma of Mascaro – subungual papule BJD 144:625–627, 2001 Digital fibrous tumor of childhood – toe nodule AD 131:1195, 1198, 1995 Digital myxoid cyst Derm Surg 27:591–593, 2001 Eccrine angiomatous hamartoma – vascular nodule; macule, red plaque, acral nodule of infants or neonates; painful, red, purple,

Osteoma cutis – personal observation Poroma – painful acral verrucous papule of fingertip AD 144:1051– 1056, 2008 Recurrent infantile digital fibromatosis AD 138:1246–1251, 2002 Squamous cell carcinoma Derm Surg 27:591–593, 2001; subungual squamous cell carcinoma JAAD 11:291–298, 1984 Trichilemmal cyst Hand Surg 19:1331–133, 2014

PARANEOPLASTIC DISORDERS Clubbing – non-small cell lung cancer NEJM 375:1171, 2016

PRIMARY CUTANEOUS DISEASES Clubbing, congenital – mutation in SLCO2A1 bjd 177:546–548, 2017 Erythema elevatum diutinum BJD 143:415–420, 2000 Granuloma annulare JAAD 3:217–230, 1980

Fingertip Lesions Juvenile plantar dermatosis – toe tips Clin Exp Dermatol 11:529– 534, 1986; Semin Dermatol 1:67–75, 1982; Clin Exp Dermatol 1:253–260, 1976 Lichen planus Lichen striatus Skin Appendage Disorders 3:188–189, 2017 Pustular psoriasis; acrodermatitis continua of Hallopeau Psoriasis (Auckl)9:65–72, 2019

431

Maffucci's syndrome – enchondromas, angiomas, cartilaginous; Dermatologic Clinics 13:73–78, 1995; JAAD 29:894–899, 1993 Multicentric reticulohistiocytosis – digital papules AD 140:919–921, 2004; JAAD 49:1125–1127, 2003; AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601– 608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968 Neurofibromatosis – digital papule

Factitial dermatitis

No fingerprint syndromes – Naegeli-Franceschetti-Jadassohn syndrome, X-linked hypohidrotic ectodermal dysplasia, RappHodgkin syndrome, AEC syndrome Jorgenson’s syndrome, Basan’s syndrome, dermatopathia pigmentosa reticularis JAAD 50:782, 2004

SYNDROMES

Pachydermodactyly – benign fibromatosis of fingers of young men AD 129:247–248, 1993; JAAD 27:303–305, 1992; AD 111:524, 1975

Blue rubber bleb nevus syndrome

Peutz-Jegher syndrome

Carney complex – non-blanching annular and serpiginous macules of digital pads JAAD 46:161–183, 2002

Proteus syndrome Ped Derm 5:14–21, 1988

PSYCHOCUTANEOUS DISEASES

CHILD syndrome – fingertip nodules (verruciform xanthomas) JAAD 50:S31–33, 2004 Ectodermal dysplasia Familial multiple acral mucinous fibrokeratomas – verrucous papules of the fingers JAAD 38:999–1001, 1998 Fetal hydantoin syndrome – hypertrichosis, broad depressed nasal bridge, large lips, wide mouth, short webbed neck, short stature, hypoplastic distal phalanges JAAD 46:161–183, 2002

PTEN hamartoma-tumor syndrome – neuromas of fingers, palms; corneal nerve hypertrophy AD 142:625–632, 2006 Reactive arthritis Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – papules, annular targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAAD 21:374–377, 1989 Tuberous sclerosis – digital papules J Clin Neurol 7:221–224, 1992; Koenen’s tumors JAAD 62:159–161, 2010

Fibroblastic rheumatism – symmetrical polyarthritis, nodules over joints and on palms, elbows, knees, ears, neck, Raynaud’s phenomenon, sclerodactyly; joint contractures, thick palmar fascia; scalp nodules, red tender swelling of toe tips, periarticular nodule; skin lesions resolve spontaneously JAAD 66:959–965, 2012; Ped Derm 19:532–535, 2002; AD 131:710–712, 1995

TOXINS

Haim-Munk syndrome (arachnodactyly, acro-osteolysis, atrophic nail changes) Cutis 93:193–198, 2014

TRAUMA

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) Am J Med 82:989–997, 1987

Calluses

HOPP syndrome – hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, lingua plicata, onychogryphosis, ventricular arrhythmias, periodontitis BJD 150:1032–1033, 2004; BJD 147:575–581, 2002 Hypereosinophilic syndrome – digital ulcers Semin Dermatol 14:122–128, 1995 Incontinentia pigmenti – painful subungual keratotic tumors JAAD 13:913–918, 1985 Infantile digital fibromatosis JAAD 49:974–975, 2003 Juvenile hyaline fibromatosis – pearly white papules of face and neck; larger papules and nodules around nose, behind ears, on fingertips, knuckle pads; multiple subcutaneous nodules of scalp, trunk, and extremities, papillomatous perianal papules; joint contractures, skeletal lesions, gingival hyperplasia, stunted growth AD 121:1062–1063, 1985; AD 107:574–579, 1973 Laband syndrome (hereditary gingival fibromatosis) – soft, large floppy ears; bulbous soft nose, gingival fibromatosis; absent nails; atrophic distal phalanges, hyperextensible joints, hepatosplenomegaly, hypertrichosis, mental retardation Ped Derm 10:263–266, 1993; J Otol Pathol Med 19:385–387, 1990; Oral Surg Oral Med Oral Pathol 17:339–351, 1964 Lipoid proteinosis – acral papules BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002; digital papule AD 132:1239–1244, 1996

Silica-associated systemic sclerosis BJD 123:725–734, 1990

Chilblains (perniosis) – tender, pruritic red or purple digital papules Mayo Clin Proc 89:207–215, 2014; JAAD 45:924–929, 2001; plantar nodule Ped Derm 15:97–102, 1998 Ectopic nail – acquired post-traumatic ectopic nail (onychoheterotopia) SKINmed 12:306–307, 2014 Friction blister Guitarist’s fingers Harpists’ fingers – paronychia with calluses of the sides and tips of fingers with onycholysis and subungual hemorrhage Trauma – crush injuries Injury 29:447–450, 1998

VASCULAR DISEASES Angiokeratoma of Mibelli – acral vascular papules JAAD 45:764– 766, 2001 Arteriosclerotic peripheral vascular disease – acral livedo, cyanosis, necrosis Arteriovenous malformation, digital – red papule, subungual blue papule BJD 147:1007–1011, 2002; BJD 136:472–473, 1997 Cholesterol emboli AD 122:1194–1198, 1986 Glomus tumor, subungual Derm Surg 27:591–593, 2001; J Hand Surg 22:508–510, 1997 Hemangiomas

432 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Hypersensitivity vasculitis Microscopic polyarteritis – digital ulcer AD 128:1223–1228, 1992 Neonatal hemangiomatosis – digital papule Pigmented purpuric eruptions Polyarteritis nodosa – cutaneous infarcts presenting as tender nodules; distal gangrene J Korean Med Sci 21:371–373, 2006 Pyogenic granuloma Derm Surg 27:591–593, 2001 Raynaud’s phenomenon NEJM 368:1344, 2013 Recurrent cutaneous eosinophilic vasculitis – pruritic violaceous swelling of fingertips BJD 149:901–902, 2003 Reperfusion bullae after cardiac arrest – personal observation Granulomatosis with polyangiitis – digital ulcer BMJ Case Rep Feb 22, 2019; Am J Case Rep 19:1701–1703, 2018; AD 130:861–867, 1994 Varix – personal observation

FINGERTIP NECROSIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Antineutrophil cytoplasmic antibody syndrome – purpuric vasculitis, orogenital ulceration, fingertip necrosis, pyoderma gangrenosumlike ulcers BJD 134:924–928, 1996 Antiphospholipid antibody syndrome – petechiae, purpura, ecchymoses, splinter hemorrhages Dermatol Clin 33:207–241, 2015; BJD 157:389–392, 2007; Semin Arthritis Rheum 31:127–132, 2001; JAAD 36:149–168, 1997; JAAD 36:970–982, 1997; BJD 120:419– 429, 1989; neonatal digital gangrene AD 143:121–122, 2007; Semin Thromb Hemost 20:71–78, 1994 Connective tissue disease – eosinophilic vasculitis in connective tissue diseases; digital microinfarcts JAAD 35:173–182, 1996

Mixed connective tissue disease – vasculitis Am J Med 52:148–159, 1972 Rheumatoid vasculitis – purpuric infarcts of paronychial areas and digital pads (Bywater’s lesions) JAAD 53:191–209, 2005; BJD 77:207–210, 1965; digital infarcts JAAD 48:311–340, 2003 Scleroderma, including CREST syndrome Sjogren's syndrome STING-associated vasculopathy with onset in infancy (Activated STING in Vascular and Pulmonary syndrome) – autoinflammatory disease; butterfly telangiectatic facies; red facial plaques, acral violaceous psoriasiform plaques and acral cyanosis, papulosquamous and atrophic plaques of vasculitis of hands; distal ulcerative lesions with infarcts, gangrene of fingers or toes, nodules of face, nose, and ears; nasal septal perforation, nail dystrophy; fingertip ulcers with necrosis; paratracheal adenopathy, abnormal pulmonary function tests; interstial lung disease with fibrosis; polyarthritis; myositis gain of function mutation in TMEM173 (stimulator of interferon genes) JAAD 74:186–189, 2016; NEJM 371:507–518, 2014

CONGENITAL LESIONS Umbilical artery catheterization – acrocyanosis, necrosis, livedo reticularis Textbook of Neonatal Dermatology, p. 108, 150, 2001

DEGENERATIVE DISEASES Peripheral neuropathy

DRUG-INDUCED Beta blockers – acral finger/toe-tip arteritis BJD 152:166–169, 2005 Bleomycin, intralesional treatment of warts; sclerodermatous changes of hands with digital gangrene Clin Rheumatol 18:422– 424, 1999; JAAD 33:851–852, 1995; AD 107:553–555, 1973; Raynaud’s phenomenon

Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – loss of function mutation in cat eye syndrome chromosome candidate 1 gene (CECR1); painless leg nodules with intermittent livedo reticularis, Raynaud’s phenomenon, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae; vasculitis of small and medium arteries with necrosis, fever, early recurrent ischemic and hemorrhagic strokes, peripheral and cranial neuropathy, and gastrointestinal involvement (diarrhea); hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:199–201, 2020; NEJM 380:1582–1584, 2019; Ped Derm 33:602–614, 2016; NEJM 370:911–920, 2014; NEJM 370:921–931, 2014

Bleomycin, vincristine, and methotrexate BJD 134:378–379, 1996

Dermatomyositis – tender hyperkeratotic palmar papules in palmar creases of fingers with central white coloration; dermatomyositis with MDA-5 (CADM-40) (melanoma differentiation-associated gene 5) MDA 5 – RNA-specific helicase; all with interstitial lung disease; ulcers of nail folds, Gottron’s papules, and elbows; these patients demonstrate oral ulcers, hair loss, hand edema, arthritis/arthralgia, diffuse hair loss, punched out ulcers of shoulder or metacarpophalangeal joints, digital necrosis, erythema of elbows and knees (Gottron’s sign), and tender gingiva JAAD 78:776–785, 2018; JAAD 65:25–34, 2011

Heparin-induced thrombocytopenia observation Foot Ankle Surg 50:16–24, 2011; Am J Med 118 suppl18A:215–305, 2005

Hypersensitivity angiitis AD 138:1296–1298, 2002 IgG4 disease – Raynaud’s phenomenon, digital gangrene, and hyperglobulinemic purpura BJD 165:1364–1366, 2011 Lupus erythematosus – systemic; vasculitis with infarcts of fingertips JAAD 48:311–340, 2003; JAMA 181:366–374, 1962

Buprenorphine – intra-arterial injection AD 138:1296–1298, 2002 Calcium channel blockers – acral finger/toe-tip arteritis BJD 152:166–169, 2005 Cisplatin BJD 142:833–834, 2000 Coumarin necrosis Cyclosporine vasculopathy Ergotamine alkaloids – acral finger/toe-tip arteritis BJD 152:166– 169, 2005 Gemcitabine Eur J Cancer 19:408–409, 2010

Immune checkpoint inhibitors BMC Cancer 19:449, 2019; BMC Cancer 17:327, 2017 Levophed – ischemic necrosis – personal observation Mephedrone Plast Reconstr Surg Glob Open 6:e1906, 2018 Oxymetazoline – intra-arterial injection AD 138:1296–1298, 2002 Quinine sulfate Hautarzt 51:332–335, 2000; quinine-induced thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome J Postgrad Med 48:197–198, 2002 Vasculitis, drug-induced AD 138:1296–1298, 2002 Vasoconstrictors (vasopressors) infusion; peripheral ischemia NEJM 369:1047–1054, 2013

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EXOGENOUS AGENTS

METABOLIC

Cannabis arteritis (marijuana) – acral toe-tip necrosis over legs JAAD 69:135–142, 2013; BJD 152:166–169, 2005; Arch Mal Coeur 53:143–147, 1960

Anticardiolipin antibodies with leukocytoclastic vasculitis – personal observation

Levamisole-contaminated cocaine J Burn Care Res 33:e6–11, 2012 Dandelion tea – hyperoxalemia BJD 169:227–230, 2013

Calcific arteriopathy of chronic renal failure (calcific uremic arteriolopathy) – personal observation The Ochsner Jnl 14:380– 385, 2017

Dieffenbachia seguine – metalloproteinase BJD 162:1150–1152, 2010

Calcinosis cutis – metastatic calcification; calciphylaxis JAAD 45:35–361, 2001; Arch Int Med 136:1273–1280, 1976

Parenteral nutrition – extravasation of parenteral nutrition in pre-term or low birth weight infants; edema and compartment syndromes; necrosis, acral necrosis, anonychia Ped Derm 32:830–835, 2015

Calciphylaxis NEJM 378:1704–1714, 2018; Lancet Diabetes Endocrinol 2:90, 2014

Mitten thread JAMA 248:924–925, 1982 Silica-associated systemic sclerosis BJD 123:725–734, 1990

INFECTIONS AND INFESTATIONS Acute bacterial endocarditis, Staphylococcus aureus – personal observation Anthrax – eschar of the fingers, face, or neck Cutis 67:488–492, 2001; Clin Inf Dis 19:1009–1014, 1994; Cutis 48:113–114, 1991; Cutis 40:117–118, 1987 Aspergillosis – primary cutaneous JAAD 31:344–347, 1994 Cowpox – human cowpox with fingertip necrosis and arm abscess, lymphangitis, lymphadenopathy Clin Inf Dis 69:179–181, 2019 Eikenella corrodens – felon with fingertip necrosis Diabetes Care 19:1011–1013, 1996 Epidemic typhus (Rickettsia prowazeki) – pink macules on sides of trunk, spreads centrifugally; flushed face with injected conjunctivae; then rash becomes deeper red, then purpuric; gangrene of finger, toes, genitalia, nose JAAD 2:359–373, 1980 Felon with fingertip necrosis Diabetes Care 19:1011–1013, 1996 Hepatitis C – with cryoglobulins; thrombotic vasculitis AD 131:1185– 1193, 1995; necrolytic acral erythema An Bras Dermatol 94:446– 448, 2019 Herpes simplex virus in AIDS HIV AD 131:357–358, 1995; polyarteritis nodosa-like lesions J Clin Inf Dis 23:659–661, 1996 Malaria Med Port 16:369–371, 2003; symmetric peripheral gangrene due to falciparum malaria J Assoc Physicians India 52:498–499, 2004 Meningococcemia Curr Prob in Dermatol 14:183–220, 2002 Mucormycosis – personal observation Mycoplasma pneumoneae – cold agglutinins Croat Med J 58:424– 430, 2017 Osteomyelitis – personal observation Pasteurella canis due to dog bite JAAD 46:S151–152, 2002

Anti-thrombin III deficiency

Cholesterol emboli – personal observation Cryofibrinogenemia Cryoglobulinemia Arthritis Rheum 42:1051–1955, 1999; type I cryoglobulinemia; monoclonal IgM cryoglobulinemia – bilateral fingertip necrosis NEJM 370:1148, 2014 Diabetes mellitus – diabetic gangrene Dermatol Clin 33:207–241, 2015; micrangiopathy; neuropathic ulcers; pseudoainhum in diabetics necrosis from finger sticks – personal observation Factor V Leiden deficiency, heterozygous BJD 143:1302–1305, 2000 Functionally abnormal plasminogen Hyperhomocysteinemia – distal cutaneous necrosis Ann DV 126:822–825, 1999 Hyperviscosity – acral finger/toe-tip necrosis JAAD 60:1–20, 2009; BJD 152:166–169, 2005 Primary hyperoxaluria (alanine glyoxalate aminotransferase deficiency – livedo reticularis AD 147:1302–1305, 2011; JAAD 46:S16–18, 2002; AD 136:1272–1273, 2000; JAAD 22:952–956, 1990; Clin Exper Dermatol 16:367–370, 1991; peripheral (digital) ischemia Hemodial Int 13:266–270, 2009; AD 136:1272–1274, 2000; ulcers AD 131:821–823, 1995  Primary hyperoxaluria type I – decreased peroxisomal, liverspecific alanine glyoxylate aminotransferase BJD 169:227–230, 2013  Primary hyperoxaluria type II – glyoxylate/hydroxypyruvate reductase; GRHPR gene mutation BJD 169:227–230, 2013  Primary hyperoxaluria type III – decreased 4-hydroxy 2-oxyglutarate aldolase BJD 169:227–230, 2013 Protein C or S deficiency Waldenstrom's macroglobulinemia

NEOPLASTIC Gamma heavy chain disease JAAD 23:988–990, 1990 Lymphoma – cutaneous T-cell lymphoma with gangrene JAAD 23:1169–1170, 1990; angiocentric lymphoma BJD 142:1013–1016, 2000 Metastatic carcinoma – gastric, breast lung, kidney, colon JAAD 27:117–118, 1992

Plague – septicemic plague; shock, purpura and ecchymoses, digital gangrene JAAD 65:1213–1218, 2011

Myeloid metaplasia Ann Surg 193:453–461, 1981

Rocky Mountain spotted fever (Rickettsia rickettsii) – initially blanching pink macules, or morbilliform eruption of wrists and ankles; soon spreads to face, trunk, and extremities; palms and soles involved; becomes purpuric with acral gangrene JAAD 2:359–373, 1980

Thrombocythemia Leuk Lymphoma 22 Suppl 1:47–56, 1996

Septic emboli Snakebite – African puff adder J Emerg Med 15:827–831, 1997 Staphylococcal cellulitis – personal observation

Polycythemia vera Vasc Med 11:35–37, 2006

PARANEOPLASTIC DISORDERS Paraneoplastic acral vascular syndrome – acral cyanosis and gangrene JAAD 70:393–395, 2014; JAAD 60–1–20, 2009; JAAD 47:47–52, 2002; AD 138:1296–1298, 2002; Br Med J iii:208–212, 1967

434 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

SYNDROMES Behcet's disease with vasculitis JAAD 21:576–579, 1989 Carpal tunnel syndrome – necrotic fingertips following bullae SkinMed 13:231–232, 2015; Ped Derm 31:500–503, 2014; JAAD 29:287–290, 1993; AD 120:517–519, 1984 Hypereosinophilic syndrome – arterial occlusion BJD 144:1087– 1090, 2001; BJD 143:641–644, 2000 Familial chilblain lupus – paronychia, acral erythema, acral papules, necrotic ulcers, facial ulcers, mutilation of fingers, ear lesions; mutation of exonuclease III domain of 3’ repair exonuclease 1 (TREX1) JAMADerm 151:426–431, 2015 IgG4-related disease – cutaneous plasmacytosis (papulonodules); pseudolymphoma; angiolymphoid hyperplasia with eosinophilia; Mikulicz’s disease; psoriasiform dermatitis; morbilliform eruption; hypergammaglobulinemic purpura; urticarial vasculitis; ischemic digits; Raynaud’s disease and digital gangrene BJD 171:929, 959–967, 2014 Pseudoxanthoma elasticum – acral finger/toe-tip arteritis BJD 152:166–169, 2005 Thoracic outlet obstruction AD 138:1296–1298, 2002

TOXINS Alcoholic motor and sensory neuropathy

Eosinophilic granulomatosis with polyangiitis BJD 150:598–600, 2004 DIC, purpura fulminans, symmetric peripheral gangrene Emboli – septic, cholesterol, fat, tumor, paradoxical, mural thrombus, atrial myxoma Erythromelalgia – associated with thrombocythemia – may affect one finger or toe; ischemic necrosis JAAD 22:107–111, 1990 Granulomatosis with polyangiitis BMJ Case Rep Feb 22, 2019; Am J Case Rep 19:1071–1073, 2018; AD 130:861–867, 1994 Peripheral digital ischemia – thrombotic microangiopathy (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome) J Invest Med 50:201–206, 2002 Polyarteritis nodosa (systemic or cutaneous PAN) – digital infarction JAAD 48:311–340, 2003; Ann Rheum Dis 54:134–136, 1995; Cutis 46:53–55, 1990; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014 Radial artery removal for coronary bypass grafting AD 138:1296– 1298, 2002 Raynaud's phenomenon/disease JAAD 59:633–653, 2008; J Rheumatol 19:1286–1288, 1992 Thoracic outlet syndrome/obstruction AD 138:1296–1298, 2002

TRAUMA

Thromboangiitis obliterans (Buerger’s disease) Am J Med Sci 136:567–580, 1908

Blunt trauma – repetitive blunt trauma AD 138:1296–1298, 2002

Thromboembolic phenomena – cardiac source, arterial source, aneurysm (subclavian or axillary arteries), infection, hypercoagulable state; marantic endocarditis AD 138:1296–1298, 2002

Chilblains – with necrosis on fingers, toes, nose, and ears in patients with monocytic leukemia AD 121:1048, 1052, 1985 Compartment syndrome – crush injury of thorax AD 138:1296– 1298, 2002

Thrombotic thrombocytopenic purpura JAAD 60:1–20, 2009

Crutch pressure arteritis

Vascular trap syndrome – acral finger/toe-tip necrosis BJD 152:166–169, 2005

Dialysis shunt-associated steal syndrome – acral finger necrosis JAAD 70:393–395, 2014; Ann Dermatol Venereol 133:264–267, 2006; Curr Surg 63:130–136, 2006; AD 138:1296–1298, 2002

Thrombotic vasculopathy – personal observation

Electric shock AD 138:1296–1298, 2002

Vasculitis – multiple types; acral finger/toe-tip necrosis Sem Arthr Rheum 43:681–688, 2014; BJD 152:166–169, 2005; ANCAassociated necrotizing vasculitis Clin Kidney J 6:240–242, 2013

Frostbite

Vasospasm from arterial puncture

Hypothenar hammer syndrome JAAD 34:880–883, 1996

Venous limb gangrene – during warfarin treatment of cancer-associated deep venous thrombosis; necrosis of of toes and foot; due to severe depletion of protein C and failure to reduce thrombin generation Ann Int Med 135:589–593, 2001

Pressure necrosis – personal observation Radial or ulnar artery cannulation AD 138:1296–1298, 2002; Hand Surg 4:151–157, 1999; N Y State J Med 90:375–376, 1990 Vibration syndrome AD 121:1544–1547, 1985

VASCULAR Arterial fibromuscular dysplasia AD 138:1296–1298, 2002 Arteriosclerosis – peripheral vascular disease Dermatol Clin 33:207–241, 2015; AD 138:1296–1298, 2002 Arteriovenous fistulae – vascular steal syndrome in hemodialysis patients (dialysis-associated steal syndrome) with arteriovenous fistulae JAAD 58:888–891, 2008; AD 138:1296–1298, 2002

FINGERTIP ULCERS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Dermatomyositis – anti-MDA5 antibodies; fingertip ulcers JAAD 78:776–785, 2018; calcinosis JAMADerm 150:724–729, 2014 Familial chilblain lupus – autosomal dominant; TREX1 mutation JAMADerm 155:342–346, 2019

Atrial fibrillation with emboli

Hypersensitivity angiitis AD 138:1296–1298, 2002

Cardiogenic shock

PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of

Congenital fibromuscular dysplasia BJD 163:1362–1364, 2010; J Vasc Surg 46:803–807, 2007

Fingertip Ulcers nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAMADerm 151:627–634, 2015 Rheumatoid vasculitis JAAD 17:355–359, 1987; Clin Rheumatol 2:3210330, 1983 Scleroderma – digital ulcers J Hand Surg 9:320–327, 1984; ulnar artery occlusion Arthr Rheum 71:983–990, 2019 Sclerodermatomyositis – Gottron’s papules, periorbital erythema, Raynaud’s phenomenon, acrosteolysis, dysphagia, digital ulcers; high risk of interstitial lung disease Arthr Research Therapy 16:R111, 2014; AD 144:1351–1359, 2008; Arthr Rheum 50:565– 569, 2004; J Clin Immunol 4:40–44, 1984

Streptococcal gangrene – nail degloving JAAD 58:232–237, 2008 Syphilis – primary chancre AD 141:1303–1310, 2005 Tularemia – Francisella tularensis NEJM 372:954–962, 2015; MMWR 51:181–184, 2002

INFILTRATIVE DISORDERS Primary systemic amyloidosis Dermatologica 183:44–46, 1991

INFLAMMATORY DISEASES Pyoderma gangrenosum JAAD 18:1084–1088, 1988; JAAD 16:141–142, 1987

CONGENITAL LESIONS

METABOLIC DISEASES

Congenital insensitivity to pain Cutis 51:373–374, 1993

Bullous dermatosis of hemodialysis JAAD 21:1049–1051, 1989

DEGENERATIVE DISEASES

435

Calcinosis cutis – CREST/dystrophic/chronic renal failure J Rheumatol 20:1233–1235, 1993 Cryofibrinogenemia – toe ulcers AD 144:405–410, 2008

Peripheral neuropathy – alcoholic, diabetic

Diabetic neuropathic ulcers – personal observation

Stroke with neuropathic ulcers – personal observation

Gamma heavy chain disease JAAD 23:988–990, 1990

Syringomyelia – fingertip ulcers with resorption of phalanges

Oxalate granuloma JAAD 22:316–318, 1990 Tyrosinemia type II – erosions Ped Derm 1:25–34, 1983

DRUGS Buprenorphine – intra-arterial injection AD 138:1296–1298, 2002

NEOPLASTIC DISEASES

Diphenhydramine injected periungually JAAD 21:1318–1319, 1989

Acquired subungual exostoses JAAD 26:295–298, 1992

Ergotamine abuse Ipilimumab Ann DV Dec 18, 2019

Aggressive digital papillary adenocarcinoma – ulcer of fingertip AD 146:191–196, 2010

Oxymetazoline – intra-arterial injection AD 138:1296–1298, 2002

Basal cell carcinoma JAAD 23:318–319, 1990

Toxic epidermal necrolysis – nail degloving JAAD 58:232–237, 2008

Epithelioid sarcoma AD 148:849–854, 2012; JAAD 14:893–898, 1986

Vasculitis, drug-induced AD 138:1296–1298, 2002

EXOGENOUS AGENTS Cannabis arteritis JAAD 58:S65–67, 2008 Silica dust – occupational scleroderma; digital ulcers, interstitial lung disease, myocardial dysfunction, cancer JAAD 72:456–464, 2015

INFECTIONS Blistering distal dactylitis JAAD 14:310–311, 1987

Lymphoma – cutaneous T-cell lymphoma with gangrene JAAD 23:1169–1170, 1990; angiocentric lymphoma BJD 142:1013–1016, 2000 Melanoma, subungual amelanotic – ulcerated nodule of nail bed JAMA 319:713–714, 2018 Metastatic gastric carcinoma Mucoepidermoid carcinoma BJD 149:1091–1092, 2003 Myxoma JAAD 22:343–345, 1990 Polycythemia vera Squamous cell carcinoma – subungual Dermatologica 150:186– 190, 1975

Fusarium JAAD 47:659–666, 2002 Herpes simplex infection, chronic in HIV disease; in leukemia JAAD 60:484–486, 2009 Leprosy Mycobacterium terrae – hyperkeratotic plaque and osteomyelitis following metal staple puncture BJD 152:727–734, 2005 Orf BJD 178:547–550, 2018 Osteomyelitis with lymphostasis – personal observation Osteomyelitis with Chiari malformation – personal observation Sporotrichosis – finger ulcer Cutis 69:371–374, 2002

PARANEOPLASTIC DISORDERS Paraneoplastic acral vascular syndrome – acral cyanosis and gangrene JAAD 47:47–52, 2002; AD 138:1296–1298, 2002

PRIMARY CUTANEOUS DISEASES Lichen planus, erosive JAAD 21:1076–1080, 1989; nail degloving JAAD 58:232–237, 2008; denudation of toes Cutis 102:131–135, 2018

436 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

SYNDROMES Activated STING in Vascular and Pulmonary syndrome – autoinflammatory disease; butterfly telangiectatic facies; acral violaceous psoriasiform, papulosquamous and atrophic plaques of vasculitis of hands; nodules of face, nose, and ears; fingertip ulcers with necrosis; nail dystrophy; nasal septal perforation; interstitial lung disease with fibrosis; polyarthritis; myositis NEJM 371:507–518, 2014 Behcet's diseases with vasculitis JAAD 21:576–579, 1989

Dialysis shunt-associated steal syndrome (hemodialysis accessinduced distal ischemia) J Cardiol Cases 20:155–157, 2019; Ann Dermatol Venereol 133:264–267, 2006; Curr Surg 63:130–136, 2006; AD 138:1296–1298, 2002 Digital ischemia – nail degloving JAAD 58:232–237, 2008 Disseminated intravascular coagulation – nail degloving JAAD 58:232–237, 2008 Emboli – from cardiac myxomas BJD 147:379–382, 2002; nail degloving JAAD 58:232–237, 2008

Carpal tunnel syndrome – acral ulcers and acro-osteolysis Neurol Sci 35:123–124, 2014; BJD 150:166–167, 2004; JAAD 29:284–290, 1993

Erythromelalgia – associated with thrombocythemia – may affect one finger or toe; ischemic necrosis JAAD 22:107–111, 1990

Compartment syndrome – crush injury of thorax AD 138:1296– 1298, 2002

Granulomatosis with polyangiitis Cutis 32:41–51, 1993

Congenital insensitivity to pain – ulcers of fingers, lips, tongue, excoriations of face BJD 179:1135–1140, 2018

Hypersensitivity vasculitis

Hereditary sensory and autonomic neuropathy type II – acral whitlows and ulcers of fingers with mutilation Hereditary sensory and autonomic neuropathy with phospholipid excretion JAAD 21:736–739, 1989 Hypereosinophilic syndrome – digital ulcers Semin Dermatol 14:122–128, 1995 Incontinentia pigmenti – painful subungual keratotoic tumors JAAD 13:913–918, 1985 Reflex sympathetic dystrophy

Essential thrombocythemia JAAD 24:59–63, 1991 Histiocytoid hemangioma JAAD 21:404–409, 1989 Microscopic polyarteritis nodosa AD 128:1223–1228, 1992 Parkes-Weber syndrome – hypertrophy with pulasatile dilated veins and arteries, palpable thrill, giant arteriovenous malformation NEJM 371:2114, 2014 Polyarteritis nodosa Radial artery removal for coronary bypass grafting AD 138:1296– 1298, 2002 Raynaud's disease/phenomenon Rheumatology (Oxford)55:1083–1090, 2016

Thoracic outlet obstruction AD 138:1296–1298, 2002

Thromboangiitis obliterans (Buerger’s disease) Am J Med Sci 136:567–580, 1908

TOXINS

Thromboembolic phenomena – cardiac source, arterial source, aneurysm (subclavian or axillary arteries), infection, hypercoagulable state AD 138:1296–1298, 2002

Acute dioxin exposure JAAD 19:812–819, 1988

Ulnar artery aneurysm Vasculitis – nail degloving JAAD 58:232–237, 2008

TRAUMA Blunt trauma – repetitive blunt trauma AD 138:1296–1298, 2002 Crush injury AD 138:1296–1298, 2002

FLUSHING DISORDERS

Electric shock AD 138:1296–1298, 2002

JAAD 77:391–402, 2017

Finger sticks in diabetics

1. Autonomic neural-mediated flushing (thermoregulatory) (Wet flushes)

Hand-arm vibration syndrome – Raynaud’s phenomenon with fingertip ulceration AD 143:1343–1344, 2007; Rheumatology (Oxford) 44:587–596, 2005; J Hand Surg (Br) 26:471–474, 2001; vibratory tool overuse Hypothenar hammer syndrome AD 138:1296–1298, 2002 Nail degloving due to trauma JAAD 58:232–237, 2008 Radial or ulnar artery cannulation AD 138:1296–1298, 2002; N Y State J Med 90:375–376, 1990

VASCULAR DISEASES Arterial fibromuscular dysplasia AD 138:1296–1298, 2002 Arteriosclerosis AD 138:1296–1298, 2002; arteriosclerosis obliterans in patients with chronic renal failure JAAD 57:322–326, 2007 Arteriovenous fistulae – vascular steal syndrome in hemodialysis patients with arteriovenous fistulae AD 138:1296–1298, 2002 Cholesterol embolism syndrome J Cardiovasc Med (Hagerstown)8:953–955, 2007

Angiokeratoma corporis diffusum (Fabry’s disease (alpha galactosidase A) – X-linked recessive; autonomic flushing of the extremities NEJM 276:1163–1167, 1967 Auriculotemporal syndrome (von Frey's syndrome) – damage to auriculotemporal nerve due to injury, abscess, after parotitis, surgery in parotid area; linear flush and/or sweating on cheek, over parotid region, neck, and temporal scalp after eating NEJM 382:1456, 2020; Ped Derm 26:302–305, 2009; JAAD 55:193–208, 2006; Ann Plast Surg 57:581–584, 2006; Ped Derm 17:415–416, 2000; Ped Derm 17:126–128, 2000; AD 133:1143–1145, 1997; Ann Plast Surg 29:217–222, 1992 Rev Neurol 2:97–104, 1923; after facial trauma J Oral Maxillofac Surg 55:1485–1490, 1997; parotidectomy Laryngoscope 107:1496–1501, 1997; after thyroidectomy BJD 79:519–526, 1967 Autonomic hyperreflexia JAAD 77:391–402, 2017 Blushing (physiologic flushing) - emotional Central nervous system lesions  Autonomic hyperreflexia – spinal cord lesions; flushing, headache, and sweating; hypertension, painful flexor spasm, postural hypotension JAAD 55:193–208, 2006

Flushing Disorders  Ciliary neuralgia (cluster headaches) – unilateral periorbital headache with lacrimation and conjunctival injection with unilateral flushing of the face  Destruction of the Gasserian ganglion J Neurol Neurosurg Psychiatry 46:611–616, 1983  Diencephalic autonomic epilepsy (autonomic epilepsy) – paroxysmal flushing, tachycardia, hypertension due to catecholamine release; loss of consciousness or generalized seizures with olfactory or epigastric aura; due to acute distension of the third ventricle JAAD 55:193–208, 2006  Horner’s syndrome, including congenital Horner’s syndrome – ptosis, miosis, anhidrosis; contralateral unilateral facial flushing JAAD 55:193–208, 2006; J Neurol Neurosurg Psychiatry 53:85–86; Harlequin sign – hemifacial flushing and contralateral hypohidrosis in Horner’s syndrome Ped Derm 23:358–360, 2006  Hypertensive diencephalic syndrome – hyperhidrosis and blotchy erythema of face and neck with salivation, tachycardia, and sustained hypertension   Multiple sclerosis JAAD 55:193–208, 2006   Organic psychosis AnnInt Med 98:30–34, 1983   Lesions of pons, medulla, cortex   Tumors compressing the third ventricle   Increased intracranial pressure J Neurosurg 92:1040–1044, 2000   Parkinson’s disease JAAD 55:193–208, 2006

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Spinal cord lesions Trigeminal nerve damage JAAD 55:193–208, 2006 3. Circulating vasodilator flushing IV contrast media (iohexol) – persistent erythema – personal observation ACE inhibitors – ACE is responsible for breakdown of bradykinin; its inhibition leads to accumulation of bradykinin, which in turn enhances production of vasodilators (nitric oxide, prostaglandins, epoxyecosatrienoic acids) Acipimox (nicotinic acid analog) – increase synthesis of prostacyclin JAAD 55:193–208, 2006 Adenosine 3'5' monophosphate Alizapride (anti-emetic) – dopamine and serotonin agonism JAAD 55:193–208, 2006 Aminophylline Amyl and butyl nitrite JAAD 55:193–208, 2006 Anaphylaxis – flushing, urticaria, angioedema; hypotension, upper airway edema, pulmonary symptoms, abdominal pain, rhinitis, headaches, substernal chest pain Clin Dermatol 32:800–808, 2014; JAAD 55:193–208, 2006

Cholinergic urticaria BJD 110:587–910, 1984

Anesthesia with combinations of isoflurane and fentanyl JAAD 55:193–208, 2006

Climacteric flushing – estrogen fluctuations JAAD 55:193–208, 2006

Angiotensin converting enzyme inhibitors JAAD 55:193–208, 2006

Flushing after breaking of a fever

Anti-emetics – alizapride, metoclopramide

Gustatory flushing, including congenital gustatory flushing – flushing, salivation, sweating, nasal secretion JAAD 55:193–208, 2006; Otolaryngol Head Neck Surg 104:878–880, 1991

Atropine (anticholinergic) – unknown mechanism

Harlequin syndrome – damage to sympathetic innervation of one side of face; decreased sweating and flushing on one side of face; compensatory increased sweating and flushing on normal side of face BJD 169:954–956, 2013

Brimonidine

Hyperthermia from exercise; from exogenous heat

Calcitonin gene-related peptide JAAD 55:193–208, 2006

Orthostatic hypotension JAAD 55:193–208, 2006

Calcium channel blockers – felodipine, nifedipine, amlodipine, diltiazem, verapamil JAAD 55:193–208, 2006; JAAD 45:323–324, 2001; BJD 136:974–975, 1997

Physiologic flushing – exercise, emotions, hot drinks Physiologic gustatory sweating Psychiatric or anxiety disorders JAAD 55:193–208, 2006 Spinal cord injuries – facial flushing accompanying profuse sweating of face, neck, upper trunk with lesions at or above T6 JAAD 20:713–726, 1989 Streeten syndrome – orthostatic hypotension and hyperbradykinism; purple discoloration of legs in upright posture JAAD 55:193–208, 2006

Beta blockers JAAD 55:193–208, 2006 Bromocriptine in Parkinsonism JAAD 55:193–208, 2006 Caffeine withdrawal syndrome JAAD 55:193–208, 2006 Calcitonin

Pharmacologic menopause – 4 hydroxy androsterone, danazol, doxorubicin AD 128:1408, 1992, tamoxifen, clomiphene citrate, decapeptyl, leuprolide; cancer chemotherapy – doxorubicin, alpha interferon, methramycin, cacarbazine, cisplatin Carbon monoxide poisoning Carboplatin – facial flushing JAAD 58:545–570, 2008; cisplatin, carboplatin, oxaliplatin JAAD 71:203–214, 2014

Interalia tumors of the posterior fossa

Carcinoid syndrome – face, neck, upper trunk associated with diarrhea, breathlessness, and wheeze; foregut (stomach, lung, pancreas, biliary tract) – bright red or pink geographic flush, sustained, with burning, lacrimation, wheezing, sweating; hindgut (appendix and ileum) – patchy, violaceous (cyanotic) flush, intermixed with pallor, short duration; presumably due to substance P Clin Dermatol 32:800–808, 2014; Dermaologic Clinics 26:45–57, 2008; JAAD 55:193–208, 2006; BJD 152:71–75, 2005; AD 77:86–90, 1958; edema, telangiectasia, cyanotic nose and face, rosacea Acta DV (Stockh) 41:264–276, 1961

Migraine (facial migraine) – episodic flushing, facial neuralgia, lacrimation JAAD 55:193–208, 2006

Catecholamines – vasodilatation via direct receptor effects JAAD 55:193–208, 2006

Parkinson's disease

Chemotherapeutic agents – interferon alpha2, cyclosporine A, cisplatin, dacarbazine, doxorubicin, mithramycin, tamoxifen

2. Antidromic sensorineural flushing (Dry flushes) Auriculotemporal syndrome (Frey syndrome) AD 133:1143–1145, 1997 Brain stem and trigeminal nerve involvement Diabetic autonomic neuropathy Familial dysautonomia (Riley-Day syndrome) Hyperthermia in infants

Post-herpetic gustatory flushing and sweating in distribution of scarred trigeminal nerve JAAD 55:193–208, 2006

Chlorpropamide flush Ann Int Med 95:468–476, 1981

438 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Cholinergic drugs – metrifonate, antihelminthics JAAD 55:193–208, 2006 Chylomicronemia syndrome – flushing with ingestion of alcohol Cisplatin JAAD 55:193–208, 2006; cisplatin, carboplatin, oxaliplatin – urticaria JAAD 71:203–214, 2014 Climacteric flushing – natural menopause JAAD 55:193–208, 2006 Combination anesthesia with isoflurane and fentanyl Contrast media Corticosteroids – high dose pulse methylprednisolone; oral triamcinolone JAAD 55:193–208, 2006; intrasynovial triamcinolone JAAD 55:193–208, 2006 Cyclosporine JAAD 55:193–208, 2006 Cyproterone acetate – anti-androgen with antigonadotropin properties, reduction in estrogen JAAD 55:193–208, 2006 Dacarbazine JAAD 55:193–208, 2006 Diazoxide Diltiazem – directly relaxes vascular smooth muscle cells

Mastocytosis – small pink patches, with flushing and diarrhea JAAD 77:405–414, 2017; NEJM 363:72–78, 2010; Dermatologic Clinics 26:45–57, 2008; JAAD 55:193–208, 2006 Medullary carcinoma of the thyroid – flushing of face and upper extremities; calcitonin, prostaglandins, histamine, substance P, levodopa, ketacalcin, ACTH, corticotrophin-releasing hormone Clin Dermatol 32:800–808, 2014; Dermatologic Clinics 26:45–57, 2008; JAAD 55:193–208, 2006 Metaclopramide (anti-emetic) – dopamine and serotonin agonism JAAD 55:193–208, 2006 Pulse high dose methylprednisolone – unknown mechanism Metronidazole with or without alcohol Morphine, opiates Myeloma in POEMS syndrome Dermatologic Clinics 26:45–57, 2008 Mithramycin JAAD 55:193–208, 2006 Morphine – immune and non-immune mediated histamine release JAAD 55:193–208, 2006

Disulfiram – prevents breakdown of dopamine

Neuroendocrine tumor – facial flushing, abdominal pain, diarrhea; hepatic metastases; elevated chromogranin and 5-hydroxyindoleacetic acid levels; tricuspid regurgitation NEJM 371:260, 2014

Doxorubicin JAAD 55:193–208, 2006

Neurologic flushing Clin Dermatol 32:800–808, 2014

Enkephalin analogs JAAD 55:193–208, 2006

Nicotinamide

Epidermal growth factor inhibitors JAAD 55:657–670, 2006

Nicotine JAAD 55:193–208, 2006

Etretinate

Nicotinic acid (high dose)[increased prostaglandin D 2 synthesis and release] JAAD 55:193–208, 2006; Clin Pharmacol Ther 50:66–70, 1991

Dimethyl fumarate (multiple sclerosis therapy) J Drugs Dermatol 13:1144–1147, 2014

Flutamide JAAD 55:193–208, 2006 Fumaric acid esters – used in treatment of psoriasis BJD 162:237– 238, 427–434, 2010 Glutamate Gold Gonadotropin-releasing hormone therapy in patients with prostatic cancer J North Am Menopause Soc 2:159–161, 1995 Histamine JAAD 55:193–208, 2006 Harlequin syndrome – unilateral facial flushing and sweating; invasion of 3rd thoracic nerve with sympathetic deficit; flushing is on normal side of face Dermaologic Clinics 26:45–57, 2008 Hormones – thyrotropin releasing factor, corticosteroid releasing factor Human corticotropin-releasing hormone Clin Investig 72:331–336, 1994 Hydralazine

Nifedipine – directly relaxes vascular smooth muscle cells Nitrate Nitric oxide releasers JAAD 55:193–208, 2006 Nitroglycerin – release of nitric oxide; direct effect to dilate vascular smooth muscle cells via increases in cGMP (second messenger) JAAD 55:193–208, 2006 Non-steroid anti-inflammatory agents – mast cell degranulation JAAD 55:193–208, 2006 Opiates Organic solvents – trichloroethylene vapor, n,n-dimethylformamide, n-butyraldoxime in printing industry, carbon disulfide, xylene, thiuram derivatives in rubber industry JAAD 55:193–208, 2006 Pancoast tumor in harlequin syndrome Dermatologic Clinics 26:45–57, 2008

Hypoglycemia JAAD 55:193–208, 2006

Pancreatic cell carcinoma – VIPomas (vasoactive intestinal peptide tumors), prostaglandin, gastric inhibitory polypeptide; VernerMorrison syndrome – watery diarrhea, hypokalemia, achlorhydria; lethargy, muscle weakness, nausea, vomiting, cramping abdominal pain Clin Dermatol 32:800–808, 2014; JAAD 55:193–208, 2006

Infusion reactions – hypersensitivity reaction

Papaverine

Interferon alfa-2 JAAD 55:193–208, 2006

Persantin

IL-2 reaction JAMA 258:1624–1629, 1987

Phenolic flavonoids

Iohexol – radiographic contrast medium JAAD 55:193–208, 2006

Phentolamine

Isosorbide dinitrate

Pheochromocytoma – flushing and hypertension; headaches, sweating, palpitations, apprehension and sense of impending doom, chest or abdominal pain, nausea and vomiting Clin Dermatol 32:800–808, 2014; Dermatologic Clinics 26:45–57, 2008; JAAD 55:193–208, 2006; JAAD 46:161–183, 2002

Hyperbradykininism (Streeten's syndrome) Hyperthyroidism, thyroid storm, Graves’ disease JAAD 48:641–659, 2003

Isotretinoin Kallikrein Kinins Leuprolide – luteinizing hormone agonist; inhibits gonadotropin secretion causing reduction in estrogen JAAD 55:193–208, 2006

Pilocarpine

Flushing Disorders Prostacyclin Circulation 106:1477–1482, 2002; NEJM 334:296–302, 1996 Prostaglandin D2 JAAD 55:193–208, 2006 Renal cell carcinoma – carcinoid-like syndrome caused by a prostaglandin secreting renal cell carcinoma; pituitary down-regulation Clin Dermatol 32:800–808, 2014; Dermaologic Clinics 26:45–57, 2008; JAAD 55:193–208, 2006; Arch Int Med 140:1095– 1096, 1980

439

 Herbal tea poisoning – anticholinergic – plant – ilex paraguariensis MMWR 44:193–195, 1995   Monosodium glutamate – very rare JAAD 55:193–208, 2006   Sodium nitrite JAAD 55:193–208, 2006   Sulfites – cured meats JAAD 55:193–208, 2006   Tartrazine in aspirin-sensitive individuals Hot beverages – vascular countercurrent JAAD 55:193–208, 2006 Sour foods

Reserpine

Spicy foods

Rifampin – unknown mechanism JAAD 55:193–208, 2006

Tyramine JAAD 55:193–208, 2006

Scopolamine (anticholinergic) – unknown mechanism

5. Alcohol-provoked flushing reactions JAAD 55:193–208, 2006; Pharmacol Biochem Behav 10:303–311, 1979

Serotonin syndrome – tremor, diarrhea, tachycardia, shivering, diaphoresis, mydriasis, nystagmus, hypertonicity, clonus, hyperreflexia, hypertension, hyperthermia, agitation, increased bowel sounds, spasms, salivation, flushing, delirium, rigidity, coma, metabolic acidosis, disseminated intravascular coagulation JAAD 77:391–402, 2017

Acetaldehyde – metabolite of alcohol; East Asian descent (Asian glow, Asian flush), deficiency of alcohol or aldehyde dehydrogenase JAMADerm 156:182–185, 2020; Rev Med Interne 35:303–309, 2014; JAAD 55:193–208, 2006; aldehyde dehydrogenase gene polymorphisms JAAD 77:391–402, 2017

Substance P

Aldehyde JAAD 55:193–208, 2006

Sildenafil citrate – inhibits phosphodiesterase-5 thus preventing cGMP breakdown and promotes vasodilatation JAAD 55:193–208, 2006

Antimalarials JAAD 55:193–208, 2006

Superior mediastinal neurinoma in harlequin syndrome Dermaologic Clinics 26:45–57, 2008

Carcinoid syndrome JAAD 68:189–209, 2013

Tamoxifen – estrogen receptor antagonist causes fluctuations in estrogen JAAD 55:193–208, 2006

Chlorpropamide JAAD 55:193–208, 2006; Clin Sci 67:375–381, 1984

Thyrotropin releasing hormone JAAD 55:193–208, 2006 Triamcinolone (oral and intrasynovial) – unknown mechanism Tricyclic antidepressants Vancomycin – non-specific mast cell degranulation; red man syndrome; flushing of upper body JAAD 55:193–208, 2006; NEJM 312:245, 1985 Vasodilators – nicotinic acid, niacin, nitroglycerin, phosphodiesterase type 5 inhibitors (sildenafil), amyl nitrate, butyl nitrate

Benorylate JAAD 55:193–208, 2006 Calcium carbamide JAAD 55:193–208, 2006 Chloramphenicol JAAD 55:193–208, 2006 Climacteric Diabetics taking chlorpropamide BMJ 281:620–621, 1980 Dupilumab facial flushing JAAD Case Reports 6:139–140, 2020 Disulfiram JAAD 55:193–208, 2006; disulfiram-like substance in fungus Coprinus atramentarius JAAD 55:193–208, 2006 Ethanol-induced flushing is increased in Asians and North American Native Americans Science 175:449–450, 1972; tyramine in red wines

Verapamil – directly relaxes vascular smooth muscle cells

Griseofulvin JAAD 55:193–208, 2006

Zollinger-Ellison syndrome

Higher chain alcohols JAAD 55:193–208, 2006

4. Restaurant flushing reactions

Hodgkin’s disease – acquired deficiency of aldehyde dehydrogenase-2 JAAD 55:193–208, 2006

Capsaicin in spicy foods JAAD 55:193–208, 2006 Food poisoning  Bacillus subtilis  Capsaicin  Ciguatera fish poisoning – marine algae (Gambierdiscus toxicus) sea bass, grouper, red snapper, barracuda, amberjack, surgeonfish (herbivorous species that consume coral); flushing, diarrhea, vomiting, abdominal pain, pruritus, temperature reversal, dysesthesia, diffuse tingling pain, burning tongue, gingiva, teeth, myalgia, weakness, and ataxia; ciguatoxin produced by coral reef dinoflagellate plankton species ingested by herbivorous fish; incubation period is 15 minutes to 3 hours JAAD 55:193–208, 2006   Inocybe mushroom poisoning Clin Med Res 16:16–28, 2018  Scombroid fish poisoning- incubation period is 10–30 minutes; fish tastes tangy, hot, bitter, spicy, peppery; headache, nausea, sweating, oral burning, abdominal pain, diarrhea, vomiting, and urticaria; scombroid mackerel-like fish include tuna, skipjack, bonito, albacore, and mackerel; non-scombroid fish include herring, sardine, pilchard, anchovy, mahimahi, bluefish, marlin, amberjack, yellowtail, kahala, kahawai, mahimahi AD 115:963– 965, 1979; and Japanese saury, Western Australian salmon Med J Aust 157:748–751, 1992

Hypereosinophilic syndrome – acquired deficiency of aldehyde dehydrogenase-2 JAAD 55:193–208, 2006 Ketoconazole JAAD 55:193–208, 2006 Metronidazole JAAD 55:193–208, 2006 Phentolamine JAAD 55:193–208, 2006 Pimecrolimus – flushing after alcohol ingestion JAAD 55:193–208, 2006; AD 140:1014–1015, 2004 Rosacea Clin Dermatol 32:800–808, 2014 Tacrolimus – facial flushing after alcohol ingestion JAAD 55:193– 208, 2006; NEJM 351:2740, 2004; AD 140:1542–1544, 2004; AD 140:1014–1015, 2004; JAAD 38:69–76, 1998 Topical agents – cinnamic aldehyde, sorbic acid, methylnicotinate

6. Endogenous circulating agents Autoimmunity to estrogen or progesterone Basophilic granulocytic leukemia JAAD 55:193–208, 2006; JAAD 55:1075–1077, 2006 Bronchogenic carcinoma JAAD 55:193–208, 2006 Carcinoid syndrome – personal observation Dengue hemorrhagic fever JAAD 49:979–1000, 2003

440

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Dumping syndrome JAAD 55:193–208, 2006

EXOGENOUS AGENTS

Fever JAAD 55:193–208, 2006

Betel nut chewing – autonomic and psychoneurologic effects; flushing, tachycardia, warmth, euphoria, alertness, hypotension, hyperhidrosis, myocardial infarction Clin Toxicol 39:355–360, 2001

Hantavirus hemorrhagic fever – Sin nombre virus, Black Creek Canal virus, Bayou virus, New York virus, Hantaan virus, Seoul virus, Puumala virus, Dobrava virus, Khabarovsk virus – petechial axillary rash, facial flushing, generalized purpura JAAD 49:979– 1000, 2003 Homocystinuria- malar flush JAAD 55:193–208, 2006 Horseshoe kidneys- flushing, nausea, abdominal pain (Rovsing’s syndrome) JAAD 55:1075–1077, 2006; JAAD 55:193–208, 2006 Hyperthyroidism JAAD 55:193–208, 2006 Insulinoma Mayo Clin Proc 42:547–550, 1967 Male climacteric flushing (male androgen deficiency) JAAD 55:193–208, 2006 Malignant ganglioneuroma JAAD 55:193–208, 2006 Malignant histiocytoma JAAD 55:193–208, 2006 Mastocytosis – solitary mastocytoma with generalized flushing Ped Derm 21:262–264, 2004; Hematol Oncol Clin North Am 14:537–555, 2000; Dermatology 197:101–108, 1998; JID 96:32S–38S, 1991; diffuse cutaneous mastocytosis; resembles foregut carcinoid flush Ann Int Med 59:194–206, 1963; systemic mastocytosis Leuk Res 25:519–528, 2001; urticaria pigmentosa, mast cell leukemia; telangiectasia macularis eruptive perstans – personal observation Medullary carcinoma of the thyroid – secreting calcitonin; MEN IIA, IIB – facial flushing, diarrhea, hoarseness, bone pain Clin Med Res 16:16–28, 2018; Lancet ii:63–66, 1968

Mushrooms

INFECTIONS AND INFESTATIONS Chikungunya fever – fever associated with flushing erythema of face and upper chest; headache, myalgia, arthralgia JAAD 58:308–316, 2008 Congo Crimean hemorrhagic fever (Bunyavirus) – sunburn flush Dengue fever (Flavivirus) – initially (first 24 hours) fever associated with flushing of face, neck, and chest; morbilliform eruption with islands of sparing and petechiae; aphthous ulcers, lichenoid papules, flagellate hyperpigmentation; urticarial lesions, erythemamultiforme-like lesions; headache, retroorbital pain, arthralgia, myalgia, leucopenia; incubation period 3–14 days; Aedes aegypti/A. albopictus Ped Derm 36:737–738, 2019; Indian Dermatol Online J 8:336–342, 2017; JAAD 75:1–16, 2016; JAAD 58:308–316, 2008 HIV-associated flush of childhood JAAD 18:1089–1102, 1988 Parvovirus B19 infection JAAD 58:308–316, 2008 Sandfly fever – headache, malaise, retro-orbital pain, flushing scarlatiniform erythema of face and neck Trypanosomiasis, African (Rhodesian) JAAD 60:897–925, 2009 Yellow fever

MEN II syndrome Neuroblastoma JAAD 55:193–208, 2006 Pancreatic VIPoma JAAD 55:1075–1077, 2006 Pheochromocytoma- flushing follows attack of hypertension, pallor, tachycardia, palpitations, and sweating JAAD 55:1075– 1077, 2006

INFLAMMATORY DISORDERS Constrictive pericarditis NEJM 333:45–48, 1995 Sarcoid – lupus pernio JAAD 55:193–208, 2006

Renal cell carcinoma JAAD 77:405–417, 2017; JAAD 55:1075– 1077, 2006

METABOLIC DISORDERS

Scarlet fever – flush of face and neck JAAD 58:308–316, 2008

Anxiety reactions, panic disorder

Toxic shock syndrome JAAD 58:308–316, 2008

Dumping syndrome – abdominal pain, diarrhea, flushing

Urticaria

Hyperthyroidism

Verner-Morrison syndrome (watery diarrhea syndrome) – pancreatic cholera

Hypotension – idiopathic orthostatic hypotension

VIPomas

7. Other causes  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSREGULATION Lupus erythematosus, systemic

DRUGS Anticholinergic syndrome – normal reflexes, mydriasis, hot dry red skin, urinary retention, absent bowel sounds NEJM 352, 1112– 1120, 2005 Cyclosporine BJD 142:832–833, 2000 Epidural corticosteroid injection Anesth Analg 80:617–619, 1995

Male hypogonadism (pseudocarcinoid syndrome) JAAD 55:1075– 1077, 2006 Malignant hyperthermia – cyanotic areas and bright red flushed patches, increased concentrations of end-tidal carbon dioxide, hypertonicity, hyperthermia, metabolic acidosis, hyporeflexia JAAD 55:193–208, 2006; NEJM 352:1112–1120, 2005 Menopause Ann Int Med 95:468–476, 1981 Neurologic disease JAAD 77:391–402, 2017 Ovariectomy Paroxysmal extreme pain disorder (familial rectal pain syndrome) Clin Med Res 16:29–36, 2018 Polycythemia vera

NEOPLASTIC DISORDERS Carcinoid syndrome JAMADerm 153:925–926, 2017 Ganglioneuroma

Follicular Plugging Hodgkin's disease Malignant histiocytoma Neuroblastoma

441

Heat urticaria – urticarial, angioedema, weakness, wheezing, headache, flushing, nausea and vomiting, diarrhea, tachycardia, syncope BJD 175:473–476, 2016; Periaortic surgery – trauma to mesentery with prostacyclin release JAAD 55:193–208, 2006

PARANEOPLASTIC DISORDERS Bronchogenic carcinoma JAAD 55:193–208, 2006 Carcinoid tumors JAAD 77:405–414, 2017 Gastroenteropathic neuroendocrine tumors JAAD 77:405–414, 2017 Medullary carcinoma of the thyroid gland JAAD 77:405–414, 2017 Pancreatic carcinoma NEJM 264:435–439, 1961 Pheochromocytoma JAAD 77:405–414, 2017

VASCULAR DISORDERS Emboli – from cardiac myxomas; red-violet malar flush BJD 147:379–382, 2002 Mitral stenosis – malar flush JAAD 55:193–208, 2006 Superior vena cava syndrome – substernal goiter, thrombosis or fibrosis of central venous catheters, pacemaker wires, fibrosing mediastinitis, aortic aneurysms JAAD 77:391–402, 2017

Renal cell carcinoma JAAD 77:405–414, 2017 Vasointestinal polypeptide-secreting tumors (VIPoma) – watery diarrhea (Verner-Morrison syndrome) JAAD 77:405–414, 2017

FOLLICULAR PLUGGING

PRIMARY CUTANEOUS DISEASES

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Acne rosacea JAAD 55:193–208, 2006; AD 134:679–683, 1998 Cholinergic urticaria Idiopathic JAAD 55:193–208, 2006

SYNDROMES Haber's syndrome – prominent flush of face Harlequin syndrome JAAD 77:391–402, 2017 Acquired harlequin syndrome JAAD 77:391–402, 2017 Kawasaki’s disease JAAD 58:308–316, 2008 Leigh syndrome (subacute necrotizing encephalomyelopathy) – flushing, pallor, sweating, drowsiness, restlessness; increased levels of endorphins in brain and spinal fluid JAAD 55:193–208, 2006 Mesenteric traction syndrome Clin Med Res 16:29036, 2018 POEMS syndrome – flushing mimicking carcinoid syndrome Clin Med Res 16:16–28, 2018; JAAD 55:193–208, 2006; AJM 90:646, 1991, Cutis 61:329–334, 1998; JAAD 40:808–812, 1999 Rousing syndrome

Alopecia totalis Proc R Soc Med 54:223–224, 1961 Chronic granulomatous disease – lupus-like lesions Dermatol 195:280–283, 1997 Lupus erythematosus – discoid lupus erythematosus NEJM 269:1155–1161, 1963

DRUG REACTIONS Pityriasis rubra pilaris – bevacizumab-induced Proc) Bayl Univ Med Ctr)29:335–336, 2016 Necrotizing infundibular crystalline folliculitis Am J Dermatopathol 39:764–766, 2017

EXOGENOUS AGENTS Chloracne

INFECTIONS AND INFESTATIONS Demodicidosis JAAD 21:81–84, 1989

TOXINS Arsenic poisoning – acute JAAD 55:193–208, 2006; BJD 149:757– 762, 2003 Industrial agents – trichlorethylene, n-dimethylformamide, n-butyl aldoxime, isocyanate from polyurethane

Leishmaniasis – post kala-azar leishmaniasis – nodular J Cutan Pathol 25:95–99, 1998 Leprosy – histoid leprosy Int J Dermatol Nov 26, 2019 Syphilis – alopecia with secondary syphilis Am J Dermatopathol 17(2):158–162, 1995 Trichodysplasia spinulosa

Mercury poisoning – butterfly rash, flushing, perspiration of face, palmar erythema JAAD 45:966–967, 2001 Mustard gas exposure JAAD 39:187–190, 1998; JAAD 32:765– 766, 1995; AD 128:775–780, 1992

INFLAMMATORY DISEASES Folliculitis decalvans Ped Derm 23:255–258, 2006 Hidradenitis suppurativa

TRAUMA

Perforating folliculitis

Cold urticaria - immediate cold-contact urticaria JAAD 13:636–644, 1985

Sarcoid – lichenoid sarcoidosis Ped Derm 18:384–387, 2001

Pseudofolliculitis barbae

442 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

METABOLIC DISEASES Biotin deficiency Vitamin A deficiency – phrynoderma Indian J Dermatol 56:389–392, 2011 Vitamin C deficiency – scurvy Dermatol Online J Jan15, 2016

NEOPLASTIC DISORDERS Cutaneous T-cell lymphoma J Eur Acad DV 29:964–972, 2015; J Cut Pathol 42:22–31, 2015; spiky follicular CTCL J Cut Pathol 42:164–172, 2015

Lichen planopilaris (S) (Graham-Little syndrome) Dermatol Clin 14:773–782, 1996; JAAD 22:594–598, 1990; AD Syphilol 5:102– 113, 1922 Lichen spinulosis Lichen sclerosus et atrophicus Int J Dermatol 55:1076–1081, 2016 Pityriasis rubra pilaris – dramatic follicular plugging JAAD 23(pt1)526–527, 1990 Reactive perforating collagenosis Rhinophyma Clin Exp Dermatol 15:282–284, 1990 Trichostasis spinulosa

Epidermal nevus Eruptive vellus hair cysts Fibrofolliculoma Generalized follicular hamartoma AD 131:454–8, 1995; AD 107:435–440, 1973; AD 99:478–493, 1969 Inverted follicular keratosis Milia

SYNDROMES Ichthyosis follicularis alopecia photophobia (IFAP) syndrome Am J Dermatopathol 33:403–406, 2011 KID (Keratosis-ichthyosis-deafness) syndrome Adv Skin Wound Care 32:1–6, 2019

Nevus comedonicus Nevus sebaceus Porokeratosis Porokeratotic eccrine ostial dermal duct nevus Seborrheic keratosis Steatocystoma multiplex

PHOTODERMATOSES Favre-Racouchot syndrome J Dermatol 41:642–644, 2014

PRIMARY CUTANEOUS DISEASES Acne vulgaris Alopecia mucinosa (follicular mucinosis) Dermatology 197:178–180, 1998; AD 125:287–292, 1989; JAAD 10:760–768, 1984; AD 76:419–426, 1957 Atrichia A Hautkr 55(4):210–217, 1980 CARD14 associated papulosquamous eruption J Cut Pathol Dec 17, 2019 Darier's disease Dilated pore of Winer Ectodermal dysplasia with corkscrew hairs JAAD 27:917–921, 1992 Elastosis perforans serpiginosa Erythromelanosis follicularis faciei et colli Indian J DV Leprol 74:47–49, 2008 Follicular atrophoderma

FOOT ULCERS NEJM 343:787–793, 2000

AUTOIMMUNE DISEASES Lupus erythematosus, discoid; systemic lupus with anti-phospholipid antibody syndrome J Postgrad Med 52:132–133, 2006 Rheumatoid arthritis – rheumatoid vasculitis; Felty syndrome with RA and hypersplenism

CONGENITAL DISORDERS Congenital insensitivity to pain – autosomal recessive; anhidrosis with palmoplantar keratoderma; unilateral plantar ulcer; mutation in NTRK1 Ped Derm 30:754–756, 2013 Syringomyelia

DEGENERATIVE DISORDERS Bony deformities Charcot foot Charcot-Marie-Tooth disease – late onset Charcot-Marie-Tooth disease – neuropathic foot ulcer JAAD 64:1215–1216, 2011 Neuropathy – motor, sensory, or autonomic Spinal cord lesions Radiographics 20:S279–293. 2000 Trophic ulcer

Follicular ichthyosis BJD 111:101–109, 1984 Follicular lichen planus

DRUGS

Keratosis lichenoides chronica Int J Dermatol 47:939–941, 2008

Hydroxyurea ulcer of ankle – painful foot ulcers Acta Clin Belg 68:382–383, 2013

Keratosis pilaris atrophicans Keratosis pilaris rubra J Cut Pathol 45:958–961, 2018 Kyrles's disease

Foot Ulcers

INFECTIONS AND INFESTATIONS

Epithelioid sarcoma Clin Exp Dermatol 35:263–268, 2010

Anthrax Ped Derm 27:600–606, 2010

Squamous cell carcinoma JAAD 70:1–18, 2014

Cellulitis

443

Verrucous carcinoma CMAJ 177:249–251, 2007

Diphtheria JAMADerm 151:1247–1248, 2015 Gram negative web space infection JAAD 45:537–541, 2001; AD 141:658, 2005; JAAD 8:225–228, 1983

PRIMARY CUTANEOUS DISORDERS

Infections, bacterial, mycotic, parasitic

Epidermolysis bullosa

Leishmaniasis – ulcers of dorsal and plantar surfaces in AIDS BJD 160:311–318, 2009; Dermatol Online J 14:15, 2008

Lichen planus, erosive Cutis 102:131–135, 2018

Leprosy – mal perforans; histiocytoid leprosy Int J Dermatol 45:433–434, 2008 Mycobacterium avium BJD 156:1381–1383, 2007; Mycobacterium avium complex – foot ulcer with sinus tracts Am Rev Resp Dis 106:469–471, 1972

Pustular psoriasis

PSYCHOCUTANEOUS DISORDERS Factitial

Mycobacterium tuberculosis J Med Microbiol 59;1247–1249, 2010 Mycobacterium ulcerans (Buruli ulcer)

SYNDROMES

North American blastomycosis CMAJ 174:35–36, 2006

Atypical progeroid syndrome – autosomal recessive; diffuse mottled hyperpigmentation, foot ulcers, facial dysmorphism, recurrent infections, intellectual disability; prolidase deficiency; peptidase D deficiency Ped Derm 36:926–928, 2019

Osteomyelitis – personal observation Poliomyelitis Prototheca zopfii – foot ulcer in West African rice farmer Trans R Soc Trop Med Hyg 58:448–451, 1964 Sea urchin spine – personal observation

Nevoid basal cell carcinoma syndrome – ulcer at base of toes Cutis 103:8, 14–15, 2019

Staphylococcal Streptococcal Syphilis, tabes dorsalis Trench foot (immersion foot) Clin Exp Dermatol 45:10–14, 2020 Yaws – primary yaws JAMADerm 151:1016, 2015

TRAUMA Altered foot biomechanics Fractures Intravenous drug abuse Cutis 93:185–187, 2014 Pressure, coma

INFILTRATIVE DISORDERS

Rat bite ulcer BMJ Case Rep Sept 20, 2016

Amyloidosis Radiographics 20:S279–293. 2000

Traumatic injuries

INFLAMMATORY DISORDERS

VASCULAR LESIONS

Pyoderma gangrenosum BJD 157:1235–1239, 2007

Acroangiodermatitis (pseudo-Kaposi’s sarcoma) – associated with chronic venous stasis, less frequently a complication of extremity paralysis, hemodialysis, post-traumatic arteriovenous fistula, amputated extremity, and vascular malformations Acta DV Alp Pannonica Adriato 22:49–51, 2013

METABOLIC DISORDERS Acrodermatitis enteropathica Diabetes mellitus JAAD 70:1–18, 2014 Hypertensive ulcer – personal observation Uremia Radiographics 20:S279–293. 2000

Arterial insufficiency Arteriovenous shunting Atrophie blanche (livedoid vasculopathy) J Drugs Dermatol 3:678–679, 2004 Buerger’s disease Neth J Med 64:206–209, 2006

NEOPLASMS Lymphoma – cutaneous T-cell lymphoma Kaposi’s sarcoma Radiol Case Rep 14:1495–1499, 2019 Acral lentiginous melanoma JAAD 76:S34–36, 2017; Neuroendocrinol Letter 37:12–17, 2016; Neth J Med 67:336–337, 2009; Practical Diabetes International 25:5–8, 2008; Lancet 366:1750, 2005; amelanotic melanoma disguised as diabetic foot Ulcer Diab Med 21:924–927, 2004 Dermatofibroma – ulceration of the sole J Cut Pathol 36:Suppl1:16– 19, 2009

Cholesterol embolus Arthr Rheum 101:1275–1280, 2009 Ischemia – personal observation Livedoid vasculopathy associated with anti-phosphatidylserine-­ prothrombin complex antibody – acral gangrene, foot ulcers AD 147:621–623, 2011 Obliterative vasculopathy Rheumatoid vasculitis Thrombotic vasculitis Vasculitis Clin in Dermatol 38:86–93, 2020 Venous gangrene

444 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

FRECKLING OF HANDS DRUG-INDUCED Minocin hyperpigmentation

SYNDROMES Acquired dermal melanocytosis Clin Exp Derm 41:643–647, 2016 Acromelanosis Acromelanosis albo-punctata Dermatology 224:331–339, 2012 Albright’s syndrome – melanotic macules

INFECTIONS Pinta

Centrofacial lentiginosis   Classic (Touraine)  Greither Cronkhite-Canada syndrome

INFILTRATIVE DISEASES Macular amyloidosis

Dermatopathia pigmentosa reticularis Dowling-Degos syndrome Dyschromatosis universalis hereditaria Dyskeratosis congenita

INFLAMMATORY DISEASES Post-inflammatory hyperpigmentation

NEOPLASTIC

Familial progressive hyperpigmentation Fanconi's syndrome Incontinentia pigmenti Inherited patterned lentiginosis in blacks AD 125:1231–1235, 1989 Laugier-Hunziker syndrome

Eruptive lentiginosis

Lentiginosis with hemangiomas

Generalized lentiginosis JAAD 18:444–447, 1988

Lentiginosis with nystagmus and strabismus (Pipkin)

Lentiginous mosaicism

LEOPARD syndrome

Lentigo simplex

Mendes de Costa syndrome (dystrophia bullosa, typus maculatus)

Nevus spilus JAAD 10:1–16, 1984

Mucocutaneous pigmentation with intestinal hemangiomatosis

Spitz nevi, agminated

Naegeli-Franceschetti-Jadassohn syndrome

Urticaria pigmentosum

NAME/LAMB syndromes Neurofibromatosis

PHOTODERMATOSES

Peutz-Jegher's syndrome POEMS syndrome

Melasma

Reticulate acropigmentation of Kitamura

Solar lentigines

Symmetrical dyschromatosis of the extremities (acropigmentation of Dohi)

PRIMARY CUTANEOUS DISEASES Erythema dyschromicum perstans Vitiligo, repigmenting Zosteriform reticulate hyperpigmentation

Tay's syndrome Tuberous sclerosis Xeroderma pigmentosum

GASTROINTESTINAL CANCER AND SKIN LESIONS

GASTROINTESTINAL HEMORRHAGE AND SKIN LESIONS

JAAD 68:189–209, 2013

JAAD 68:189–209, 2013

Acanthosis nigricans – intra-abdominal adenocarcinomas Bazex syndrome – psoriasiform plaques of ears, nose, and hands; palmoplantar keratoderma and paronychia; bulbous enlargement of distal phalanges with nail dystrophy AD 119:820– 826, 1983

AUTOIMMUNE DISEASES Dermatitis herpetiformis Scleroderma (systemic sclerosis) – watermelon stomach J Eur Acad Derm Vener 12:161–164, 1999

Carcinoid syndrome – flushing, scleral injection chronic facial erythema, rosacea, sclerodermoid changes, pellagrous dermatitis

INFECTIONS AND INFESTATIONS

Cowden’s syndrome – trichilemmomas, oral mucosal papillomatosis, acral keratosis, palmoplantar keratosis, sclerotic fibromas, acrochordons

Bacillary angiomatosis Gastro 109:2011–2014, 1995

Crohn’s disease – metastatic Crohn’s disease; pyoderma gangrenosum, erythema nodosum, oral aphthae, perianal abscesses, fissures, fistulae, hypertrophic skin tags

INFILTRATIVE DISORDERS Amyloidosis

Dermatitis herpetiformis – small intestinal lymphoma Dermatomyositis – photodistributed extensor erythema, heliotrope, shawl sign, holster sign

Mastocytosis Cutis 39:241–244, 1987

Gardner’s syndrome – epidermal inclusion cysts, lipomas, osteomas, congenital hypertrophy of retinal pigmented epithelium (CHIRPE)

INFLAMMATORY DISORDERS

Glucagonoma syndrome – atrophic glossitis, necrolytic migratory erythema, diffuse alopecia, blepharitis, conjunctivitis

Pyoderma gangrenosum

Crohn’s disease Ulcerative colitis

Hypertrichosis lanuginosa, acquired (malignant down) Muir-Torre syndrome – sebaceous tumors (adenomas, epitheliomas, carcinomas), keratoacanthomas

METABOLIC DISORDERS

Multicentric reticulohistiocytosis – non-Langerhans cell histiocytosis, symmetric erosive inflammatory arthritis of hands, elbows; progressively deforming and destructive; papulonodular eruptions of skin and mucosal nodules; periungual papulonodules (string of pearls)

Calciphylaxis Am J Case Rep 16:818,822, 2015; Arch Path Lab Med 122:656–659, 1998 Cryoglobulinemia - retiform purpura JAAD 82:783–796, 2020 Pellagra (Vitamin B3 deficiency)

Pancreatic panniculitis – enzyme panniculitis of lower legs, painful polyarthritis, eosinophilia; adenocarcinoma of the pancreas

Scurvy (Vitamin C deficiency)

Paraneoplastic pemphigus Australas J Dermatol 60:e168–169, 2019

NEOPLASTIC DISORDERS

Peutz-Jegher’s syndrome – lentigines of lips, buccal mucosa, acrally and periorificially; mutation in STK11

Kaposi’s sarcoma J Gastro Hepat 11:408–410, 1996

Pityriasis rotunda – round well demarcated scaly pigmented ichthyosiform patches of trunk, back, buttock and proximal extremities

Lymphoma – cutaneous T-cell lymphoma Indian J Gastro 6:239– 240, 1987; adult T-cell lymphoma BMJ Case Reports Nov 28, 2012; lymphomatoid granulomatosis Cancer 15:694–700, 1983

Plummer-Vinson syndrome – atrophic glossitis, koilonychia

Metastases – small bowel cutaneous melanoma metastases Am J Case Reports 14:536–538, 2013; gastric metastasis from cutaneous melanoma Pol Merkur Lekarski 37:235–236, 2014

Sign of Leser-Trelat – eruptive pruritic seborrheic keratoses; rapid increase in size of seborrheic keratoses; most common gastric adenocarcinoma JAAD 35:88–95, 1996

Leukemic vasculitis JAAD 82:799–816, 2020

Sister Mary Joseph Nodule – umbilical metastasis from intraabdominal malignancy

PARANEOPLASTIC DISORDERS

Tripe palms World J Gastroenterol 15:4372–4379, 2009

Acanthosis nigricans

Tylosis (Howell-Evans syndrome) – focal non-epidermolytic palmoplantar keratoderma, oral leukokeratosis, follicular hyperkeratosis; squamous cell carcinoma of esophagus

PRIMARY CUTANEOUS DISEASES

Ulcerative colitis – pyostomatitis vegetans; sterile pustules, oral aphthae, pyoderma gangrenosum, erythema nodosum

Acne rosacea and inflammatory bowel disease JAAD 76:911–917, 2017

445

446 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Degos’ disease (malignant atrophic papulosis) – C5b-9 mediated vascular injury Mod Rheum 25:480–483, 2015

SYNDROMES

Pustular psoriasis with IL-36RN mutation J Dermatol 46:73–75, 2019

Bannayan-Riley-Ruvalcaba syndrome – autosomal dominant; macrocephaly, genital lentiginosis, intestinal polyposis: PTEN mutation, multiple benign tumors in 50%

SYNDROMES

Birt-Hogg-Dube syndrome – skin fibrofolliculomas, acrochordons, pneumothorax, renal tumors; FLCN mutation Orphanet J Rare Dis July 15, 2014

Psoriasis and ulcerative colitis BJD 173:792–796, 2015

Behcet’s disease – with gastrointestinal amyloidosis Medicine 97:e11153, 2018 Blue rubber bleb nevus syndrome (Bean syndrome) J Ped Child Health 46:63–65, 2010; Trans Pathol Soc (London)11:267, 1860 Ehlers-Danlos syndrome – gastric adenocarcinoma J Med Assoc Thai 91:S166–171, 2008 Hermansky=Pudlak syndrome – oculocutaneous albinism, defective platelets lacking dense granules; granulomatous colitis; Puerto Rico Arecibo region Lipoid proteinosis Arch Path Lab Med 118:572–574, 1994 Neurofibromatosis – gastrointestinal stromal tumor(GIST) JAMASurg 149:1203–1204, 2014; rectal neuroendocrine tumors World J Gastroenterol 24:3806–3812, 2018 Peutz-Jegher’s syndrome Pseudoxanthoma elasticum (Gronblad Strandberg syndrome) Arch Pediatr 23:591–594, 2016; J Assoc Phys India 59:54–57, 2011

VASCULAR DISORDERS Bowel infarction – hypercoagulable state, embolus, DIC) retiform purpura JAAD 82:783–796, 2020 Granulomatosis with polyangiitis – blue-black necrotic non-vasculitis prepyloric lesion Middle East J Dig Dis 8:235–239, 2016 Henoch-Schonlein purpura – periumbilical purpura Am J Clin Dermatol 10:127–130, 2009; Dig Dis Sci 56:1919–1920, 2011 Hereditary hemorrhagic telangiectasia NEJM 373;e15, 2015; Lancet 11:160–162, 1907; Bull Johns Hopkins Hosp 12:333–337, 1901; Bull Mem Soc Med Hosp Paris 13:731, 1896 IgA vasculitis - retiform purpura JAAD 82:783–796, 2020 Klippel-Tranaunay-Weber syndrome World J Gastro 16:1548–552, 2010; Eur J Med Res 29:516–517, 2004 Multifocal lymphangioendotheliomatosis – congenital appearance of hundreds of flat vascular papules and plaques associated with gastrointestinal bleeding, thrombocytopenia with bone and joint involvement; spontaneous resolution Ped Derm 36:965–966, 2019; J Pediatr Orthop 24:87–91, 2004 PHACES syndrome – Dieulafoy lesions; small gastrointestinal mucosal erosion due to large caliber and persistent submucosal arteriole Ped Derm 36:902–905, 2019; J Pediatr 160:1021–1026, 2012 Polyarteritis nodosa Mt Sinai J Med 68:336–338, 2001 Sturge-Weber syndrome – cavernomatous transformation of the portal vein Rom J Morphol Embryol 48:171–175, 2007 Vasculitis JAAD 82:799–816, 2020

Constitutional mismatch repair-deficiency(CMMR-D)syndrome – lentigines and café au lait macules; childhood and adulthood development of leukemias, lymphomas, brain tumors, colonic polyposis with cancer NEJM 370:2229–2236, 2014 Cowden’s syndrome (multiple hamartoma syndrome) – autosomal dominant; PTEN mutation; trichilemmomas, acral keratosis, neuromas, hemangiomas, lipomas, fibromas, oral papillomas, polyps of gastrointestinal tract, increased risk of colorectal cancer Cronkhite-Canada syndrome – gastrointestinal polyposis, nail dystrophy, alopecia, hyperpigmentation of upper extremities or diffuse hyperpigmentation, diarrhea, weight loss, abdominal pain JAAD 63:172–174, 2010; AD 135:212, 1999; Cutis 61:229–232, 1998 Gardner’s syndrome – epidermal inclusion cysts, osteomas dental anomalies, pilomatrixomas, desmoid tumors, congenital hypertrophy of the retinal pigmented epithelium, fibromas, lipomas, leiomyomas, colon polyps; 100% malignant degeneration Juvenile polyposis syndrome – occurs with hereditary hemorrhagic telangiectasia mutations in SMAD4 and BMPR1A McCune-Albright syndrome Virchows Arch 470:391–400, 2017 Multiple endocrine neoplasia syndrome type 2B – mucosal neuromas of lips and tongue; medullated corneal nerves, distinctive facies, enlarged lips and tongue, marfanoid habitus, pheochromocytoma; RET mutation Muir-Torre syndrome – sebaceous carcinomas of eyelids, sebaceous adenomas anywhere on skin; keratoacanthomas; colonic polyps in 50% Neurofibromatosis type 1 – inflammatory polyps of gastrointestinal tract Virchows Arch 47:259–264, 2019; Int J Surg Pathol 25:65–68, 2017 Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – multiple gastric hamartomatous polyps Clin Colon Rectal Surg 29:330–335, 2016; keratocysts of jaw, hyperkeratosis of palms and soles, basal cell carcinomas, macrocephaly, frontal bossing; PTCH1 mutation Peutz-Jeghers syndrome – autosomal dominant; hamartomas or small intestines; lentigines of lips, genitalia, fingers; bilateral gynecomastia due to bilateral Sertoli cell tumors of the testes; mutation of STK11 tumor suppressor JAAD 53:660–662, 2005 Pilomatrixoma – multiple pilomatrixomas associated with myotonic dystrophy and familial gastrointestinal polyps Ped Derm 32:97–101, 2015 PTEN-related Proteus syndrome Serrated polyposis syndrome – with longstanding bowel disease Rev Esp Enferm Dig 109:796–798, 2017 Tuberous sclerosis Am J Med Genetics A 122A:335–341, 2003

GASTROINTESTINAL POLYPOSIS AND SKIN

GINGIVAL HYPERPLASIA

JAAD 68:189–209, 2013

JAAD 52:491–499, 2005

Gingival Hyperplasia 447

 UTOIMMUNE DISEASE AND DISEASES A OF IMMUNE DYSFUNCTION Chronic familial neutropenia GATA 2 deficiency BJD 178:781–785, 2018 Scleroderma J Indian Society Periodontol 16:271–274, 2012

CONGENITAL DISEASES Macrogingivae, congenital

HIV – ulcerative gingivitis; linear gingival erythema, acute necrotizing ulcerative gingivitis(ANUG), necrotizing ulcerative periodontitis Cutis 47:55–62, 1991 Histoplasmosis Clin Inf Dis 53:1118–1119, 2011 Mycobacteria, non-tuberculous Mycobacterium tuberculosis – oral lesions secondary to primary tuberculous infection elsewhere Lancet Inf Dis 18:1288, 2018; J Indian Soc Periodontol 13:106–108, 2009 Paracoccidioidomycosis – granulomatous ulcerative gingivitis Cutis 40:214–216, 1987 Periodontitis, chronic, adult or juvenile Cutis 47:55–62, 1991

DRUGS Amlodipine Calcium channel blockers - felodipine, amlodipine, diltiazem, isradipine, nicardipine, nifedipine, nitrendipine, nimodipine, oxydipine, verapamil JAAD 38:201–206, 1998; Cutis 62:41–43, 1998; Mayo Clin Proc 73:1196–1199, 1998

Verrucae vulgaris

INFILTRATIVE DISORDERS Amyloidosis J Oral Pathol Med 26:100–104, 1997; J Oral Pathol Med 23:423–428, 1994

Carbamazepine Mayo Clin Proc 73:1196–1199, 1998

Disseminated xanthosiderohistiocytosis (nodules) JAAD 11:750– 755, 1984

Cotrimoxazople J Contemp Dent Pract 4:10–31, 2003

Juvenile colloid milium JAAD 49:1185–1188, 2003

Cyclosporine JAMADerm 155:487, 2019; JAAD 63:949–972, 2010; JAAD 62:96–101, 2010; Dermatologica 172:24–30, 1986; Oral Surg 62:417–421, 1986; J Periodontol 57:771–775, 1986

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – limb contractures, sclerodermoid changes; gigantic lip fibromas, giant fibrous nodules of scalp and ears; giant nodules of frontal scalp and face; periarticular nodules of knees; gingival hypertrophy, bone deformities; mutation in gene encoding capillary morphogenesis protein 2 (ANTRX2(CMG2)) Ped Derm 23:458–464, 2006; JAAD 55:1036–143, 2006; Pediatrics 87:228–234, 1991

Erythromycin J Contemp Dent Pract 4:10–31, 2003 Estrogens in oral contraceptives Mayo Clin Proc 74:1196–1199, 1998 Ethosuximide J Contemp Dent Pract 4:10–31, 2003 Felodipine J Periodontol 76:1217, 2005 Ketoconazole J Contemp Dent Pract 4:10–31, 2003 Lamotrigine J Contemp Dent Pract 4:10–31, 2003 Lithium J Contemp Dent Pract 4:10–31, 2003

Langerhans cell histiocytosis – gingival nodules with ulcerations Curr Prob Derm 14:41–70, 2002; Oral Surg 49:38–54, 1980 Plasma cell gingivitis Cutis 47:55–62, 1991 Xanthogranulomatosis - multiple juvenile xanthogranulomas JAAD 14:405–411, 1986

Phenobarbitone J Neurol Neurosurg Psychiatry 73:601, 2002 Phenytoin J Clin Periodontol 23:165–175, 1996; Int J Derm 26:602–603, 1987

INFLAMMATORY DISEASES

Primidone J Contemp Dent Pract 4:10–31, 2003

Acute necrotizing ulcerative gingivitis(ANUG) Cutis 47:55–62, 1991

Sertaline J Contemp Dent Pract 4:10–31, 2003

Crohn's disease – swelling of lips, hyperplastic gingivitis, oral mucosa JAAD 77:795–806, 2017; JAAD 68:189–209, 2013; NEJM 342:1644, 2000

Succinimides Mayo Clin Proc 73:1196–1199, 1998 Tacrolimus J Periodontol 74:552–556, 2003 Topiramate J Contemp Dent Pract 4:10–31, 2003 Vemurafenib BJD 174:1159–1161, 2016 Vigabatrin J Contemp Dent Pract 4:10–31, 2003

Gingivitis, chronic – localized or generalized JAAD 52:491–499, 2005; marginal, hormonal Cutis 47:55–62, 1991 Inflammatory periodontal disease

Valproate sodium Mayo Clin Proc 73:1196–1199, 1998

Orofacial granulomatosis – oral ulcers, aphthous ulcers, swollen lip(s), gingivitis, and/or gingival hypertrophy JAAD 62:611–620, 2010

EXOGENOUS AGENTS Oral hygiene JAAD 52:491–499, 2005

Periodontitis – gingivitis involving the periodontal ligament and alveolar bone, leading to destruction; adult or juvenile JAAD 52:491–499, 2005; Cutis 47:55–62, 1991

Vitamin A toxicity JAAD 16:1027–1039, 1987

Peripheral giant cell granuloma AD 121:125–130, 1985 Plaque-induced gingivitis Cutis 47:55–62, 1991

INFECTIONS

Pyostomatitis vegetans JAAD 75:578–584, 2016 Sarcoidosis JAAD 77:809–830, 2017; Br J Oral Surg 21:31–35, 1983

Abscesses Bacillary angiomatosis – vascular papules or nodules on gingival, palate or floor of mouth J Oral Pathol 22:235–239, 1993 Candida gingivitis – in diabetics mimicking desquamative gingivitis J Clin Diagn Res 10:ZD 04–05, 2016 Cytomegalovirus Clin Infect Dis 37:e44–46, 2003

METABOLIC DISEASES Acromegaly Endocrine 18:207–210, 2002 Aplastic anemia Oral Surg Oral Med Oral Pathol 71:55–56, 1991

448 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Aspartylglucosaminuria – oral fibromatosis J Med Genet 36:398– 404, 1999 Chronic renal failure Pediatr Nephrol 18:39–45, 2003 Crohn’s disease – gingival hyperplasia with tags in mucobuccal fold NEJM 373:1250, 2015 Diabetes mellitus, uncontrolled - edematous gingival enlargement Fucosidosis JAAD 52:491–499, 2005

  Lymphoma   Melanoma    Melanotic neuroectodermal tumor   Metastatic retinoblastoma   Neuroblastoma   Rhabdomyosarcoma   Teratoma

Glycogen storage disease 1B(glucose-6-phosphate translocase deficiency) J Craniofac Surg 16:45–52, 2005

Metastases - due to hepatocellular carcinoma Cutis 65:107–109, 2000; medullary carcinoma of the thyroid J Periodontol 71:112–116, 2000

Hyperparathyroidism

Myofibromatosis J Clin Periodontol 29:1048–1050, 2002

Mannosidosis – autosomal recessive; gingival hypertrophy, macroglossia, coarse features, prognathism, thick eyebrows, low anterior hairline, deafness, lens opacities, hepatosplenomegaly, recurrent respiratory tract infections, muscular hypotonia, mental retardation Ped Derm 18:534–536, 2001

Nevus sebaceus of Jadassohn Int J Oral Surg 12:437–443, 1983

Mucolipidoses Ann Transl Med 6:476, 2018 Mucopolysaccharidoses Ann Transl Med 10:476, 2018 Plasminogen deficiency – rare autosomal recessive; thick wood-like pseudomembranes on mucosal surfaces ligneous conjunctivitis J Throm Thrombolysis 43:132–138, 2017 Pregnancy JAAD 52:491–499, 2005; J Int Med Res 30:353–355, 2002; J Am Dent Assoc 110:365–368, 1985 Puberty JAAD 52:491–499, 2005 Scurvy AD 145:195–200, 2009; NEJM 357:392–400, 2007; JAAD 52:491–499, 2005

Osteosarcoma- osteoblastic, fibroblastic, chondroblastic Contemp Clin Dent 3:367–369, 2012 Peripheral giant cell granuloma – red gingival papule JAAD 81:43–56, 2019 Peripheral ossifying fibroma – red gingival papule JAAD 81:43–56, 2019 Port wine stain hypertrophy in pregnancy - personal observation Verrucous carcinoma Oral Biol Craniofac Res 2:163–169, 2012

PARANEOPLASTIC DISEASES Hodgkin’s disease J Periodontol 72:107–112, 2001 Proliferative verrucous leukoplakia J Clin Anat Pathol 3:1–6, 2017

NEOPLASTIC DISEASES

PRIMARY CUTANEOUS DISEASES

Adenoid cystic carcinoma JAAD 81:59–71, 2019

Acanthosis nigricans – gingival swelling BJD 145:506–507, 2001

Cysts J Int Acad Periodontol 17:14–19, 2015

Epulis fissuratum

Epidermal nevus (verrucous nevus) – red papules of uvula, soft palate, and gingiva AD 141:515–520, 2005

Giant cell epulis

Extramedullary plasmacytoma Cutis 48:134–136, 1991

Solitary gingival enlargement

Idiopathic gingival hyperplasia J Orthod 30:13–19, 2003

Granular cell tumor, congenital JAAD 52:491–499, 2005 Kaposi’s sarcoma – purple infiltrated gingiva JAMADerm 155:370, 2019 Gen Dent 47:413–415, 1999; J Periodontol 57:159–163, 1986 Leukemia – monocytic leukemia, acute myelomonocytic leukemia J Periodontol 73:664–668, 2002; J Oral Pathol Med 31:55–58, 2002; J Can Dent Assoc 66:78–79, 2000; chronic myelomonocytic leukemia(CD56+) Leuk Lymphoma 45:415–418, 2004; granulocytic sarcoma (chloroma) Spec Care Dentist 24:65–69, 2004; Burkitt cell type acute lymphoblastic leukemia J Periodontol 74:547–551, 2003; acute lymphocytic leukemia AD 123:225–231, 1971; myelodysplastic syndrome Oral Surg Oral Med Oral Pathol 61:466–470, 1986; mixed lineage leukemia J Oral Pathol Med 31:55–58, 2002 Lymphoma – Hodgkin’s disease J Periodontol 72:107–112, 2001; non-Hodgkin’s lymphoma JAMADerm 155:342–346, 2019 Melanocytic nevus – intramucosal nevus Int J Oral Maxillofac Surg 31:330–333, 2002 Melanotic neuroectodermal tumor of infancy (odontoameloblastoma) – pigmented oral mass of early infancy Can J Plast Surg 16:41–44, 2008; J Oral Maxillogac Surg 65:1595–1599, 2007; Acta Pathol Jpn 39:465–468, 1989; Cancer 22:151–161, 1968; Beitr Pathol Anat 82:165–169, 1918; gingival and maxillary mass in 7-month-old AD 146:337–342, 2010  Differential diagnosis of rapidly growing mass of anterior maxilla in an infant: AD 146:337–342, 2010   Congenital epulis   Ewing sarcoma

SYNDROMES Amelogenesis imperfecta J Periodontol 76:1563–1566, 2005; J Clin Pediatr Dent 23:117–121, 1999 Amyloidosis of the gingiva and conjunctiva with mental retardation Borrone dermatocardioskeletal syndrome – autosomal recessive or X-linked; gingival hypertrophy, coarse facies, late eruption of teeth, loss of teeth, thick skin, acne conglobata, osteolysis, large joint flexion contractures, short stature, brachydactyly, camptodactyly, mitral valve prolapse, congestive heart failure Ped Derm 18:534– 536, 2001 CEDNIK syndrome(cerebral dysgenesis-neuropathy-ichthyosis-­ keratoderma) – microcephaly; dysmorphic face with small anterior fontanelles; pointed prominent nasal tip, small chin, inverted nipples and long toes, high palate, thick gingivae, cradle cap, sparse brittle coarse hair, scarring alopecia, fixed flexion posture; decreased SNAP 29 protein; mutation in SNARE proteins mediating vesicle trafficking; mutation in ABCA12 gene BJD 164:610–616, 2011; AD 144:334–340, 2008 Congenital cataracts, sensorineural deafness, hypogonadism, hypertrichosis, short stature – gingival hyperplasia Clin Dysmorphol 4:283–288, 1995 Congenital generalized fibromatosis – autosomal recessive; skin, muscle, bones, viscera Ped Derm 18:534–536, 2001

Gingival Hyperplasia 449 Congenital hypertrichosis lanuginosa with gingival hyperplasia Ped Derm 10:263–265, 1993; profuse hypertrichosis of lower face, trunk, and extremities with acromegalic features Plast Reconstr Surg 27:608–612, 1962 Congenital generalized hypertrichosis with gingival hyperplasia – osteochondrodysplasia, dysmorphic face Am J Med Genet 30:278–283, 2003; Am J Med Genet 47:198–212, 1993 Congenital plasminogen deficiency – autosomal recessive; chronic mucosal pseudomembranous lesions with white membranes of gingivae, and eyelids; blepharitis, gingival hyperplasia, leukoplakia, ligneous conjunctivitis; thick nodular eyelids Ped Derm 448–451, 2009 Costello syndrome - warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977 Cowden's syndrome - verrucous plaque on gingiva JAAD 11:1127– 1141, 1984 Cross syndrome – autosomal recessive; gingival fibromatosis, microphthalmia with cloudy corneas, mental retardation, spasticity, growth retardation, athetosis, hypopigmentation, silvery gray hair Ped Derm 18:534–536, 2001; J Pediatr 70:398–406, 1967 Dyskeratosis benigna intraepithelialis mucosae et cutis hereditaria – conjunctivitis, umbilicated keratotic nodules of scrotum, buttocks, trunk; palmoplantar verruca-like lesions, leukoplakia of buccal mucosa, hypertrophic gingivitis, tooth loss J Cutan Pathol 5:105– 115, 1978 Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) Ped Derm 126:176–179, 2009 Ehlers-Danlos syndrome type VIIc (dermatosparaxis) J Oral Pathol Med 32:568–570, 2003 Erdheim-Chester disease (lipogranulomatosis) Fabry’s disease (Anderson-Fabry's disease) – localized congenital gingival enlargement JAAD 52:491–499, 2005 Francois syndrome – xanthoma-like lesions, dermochondraldystrophy (osteochondrodystrophy); bilateral corneal dystrophy, gingival hypertrophy JAAD 55:1036–143, 2006 Gangliosidosis – X-linked – gingival hypertrophy, macroglossia, coarse facies, micrognathia, loose skin, inguinal hernia, delayed growth, hepatosplenomegaly, neonatal hypotonia, delayed motor development Ped Derm 18:534–536, 2001 Gingival fibromatosis (hereditary gingival fibromatosis) – autosomal dominant Ped Derm 18:534–536, 2001; J Clin Pediatr Dent 25:41–46, 2000 Gingival fibromatosis, hypertrichosis, cherubism, mental and somatic retardation, and epilepsy (Ramon syndrome) Am J Med Genet 25:433–442, 1986; (gingival fibromatosis, hypertrichosis, epilepsy, mental retardation) Develop Med Child Neurol 31:538– 542, 1989 Gingival fibromatosis-hypertrichosis syndrome (Byars-Jurkiewicz syndrome) – autosomal dominant; giant fibroadenomas of breast; hypertrichosis of face, upper extremities, midback; redundant skin; secondary kyphosis Ped Derm 18:534–536, 2001; J Pediatr 67:499–502, 1965; Plast Reconstr Surg 27:608–612, 1961 Gingival fibromatosis with distinctive facies – autosomal recessive; macrocephaly, hypertelorism, bushy eyebrows, synophrys,

downslanted palpebral fissures, flat nasal bridge with hypoplastic nares, cupid-bow mouth, high arched palate Ped Derm 18:534–536, 2001 Gingival fibromatosis with growth hormone deficiency Syndromes of the Head and Neck, p. 852–853, 1990 Gingival fibromatosis with sensorineural hearing loss (Jones) Ped Derm 18:534–536, 2001; Am J Med Genet 22:623–627, 1985 Heck’s disease (focal epithelial hyperplasia) – HPV 13,32; children and young adults SKINMed 14:395–397, 2016 Hemimaxillofacial dysplasia (segmental odontomaxillary dysplasia) (HATS – hemimaxillary enlargement, asymmetry of face, skin findings)– facial asymmetry, hypertrichosis of the face, unilateral maxillary enlargement, partial anodontia, delayed eruption of teeth, gingival thickening of affected segment, Becker’s nevus, hairy nevus (hypertrichosis), lip hypopigmentation, depression of cheek, erythema, hypoplastic teeth Ped Derm 21:448–451, 2004; JAAD 48:161–179, 2003; Oral Surg Oral Med Oral Pathol 64:445–448, 1987 Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, bilateral single palmar crease, hirsutism, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006 Hereditary angioedema J Clin Periodontol 30:271–277, 2003 Hereditary progressive mucinous histiocytosis – yellow domeshaped papules of face, gingiva, hard palate BJD 141:1101–1105, 1999 Hurler’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.118–119 Hypereosinophilic syndrome Cutis 29:490–493, 1982 HyperIgE syndrome (Job’s syndrome) J Indian Soc Periodontol 16:256–260, 2012 Hyperkeratosis palmoplantaris and attached gingival hyperkeratosis Arch Int Med 113:866–871, 1974 I-cell disease (mucolipidosis II) – puffy eyelids; small orbits, prominent eyes, fullness of lower cheeks; small telangiectasias; fish-mouth appearance, short neck; gingival hypertrophy Int J Paediatr Dent 13:41–45, 2003; Clin Genet 23:155–159, 1983; Birth Defects 5:174–185, 1969 Ichthyosis follicularis with atrichia and photophobia (IFAP) – gingival hyperplasia; collodion membrane and erythema at birth; ichthyosis; palmoplantar erythema; generalized follicular keratoses, non-scarring alopecia of scalp, eyebrows, and eyelashes, keratotic spiny follicular papules of elbows, knees, fingers, extensor surfaces, xerosis; angular cheilitis, recurrent cutaneous infections; punctate keratitis; ocular revascularizations; growth retardation; atopic dermatitis, urticaria; X-linked recessive Ped Derm 20:48–51, 2003; JAAD 46:S156–158, 2002; Am J Med Genet 85:365–368, 1999; AD 125:103–106, 1989; Dermatologica 177:341–347, 1988 Idiopathic fibrous hyperplasia Cutis 56:46–48, 1995 Julia Pastrana syndrome – congenital generalized hypertrichosis terminali – facial deformities and gingival hyperplasia Am J Med Genet 47:198–212, 1993 Juvenile hyaline fibromatosis (infantile systemic hyalinosis) (Murray-­Puretic-­Drescher syndrome) – autosomal recessive; gingival fibromatosis with hypertrophy, focal skin nodularity with multiple subcutaneous tumors (nodular perianal lesions, facial red

450 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 or pearly papules (paranasal, periauricular), dusky red plaques of buttocks, ears, lips), synophrys, thickened skin with sclerodermiform atrophy, osteolytic (osteoporotic) skeletal lesions, stiff muscles with massive stiffness, flexural joint contractures (frog leg position), hyperpigmentation, flexion contractures of joints, juxta-articular nodules (knuckle pads), nodules of ears, diarrhea, recurrent suppurative infections failure to thrive with stunted growth (growth failure) and death in infancy; CMG2 (capillary morphogenesis protein 2) (transmembrane protein); deposition of collagen type VI (bound to laminin and collagen 4) mutation (chromosome 4q21) JAAD 61:629–638, 2009; Ped Derm 25:557–558, 2008; JAAD 58:303–307, 2008; Ped Derm 21:154–159, 2004; JAAD 50:S61–64, 2004; Ped Derm 18:534–536, 2001; Ped Derm 18:400–402, 2001; Dermatology 198:18–25, 1999; Int J Paediatr Dent 6:39–43, 1996; J Periodontol 67:451–453, 1996; Dermatology 190:148–151, 1995; Ped Derm 11:52–60, 1994; Ped Derm 6:68–75, 1989; Oral Surg 63:71–77, 1987; Arch Fr Pediatr 35:1063–1074, 1978 Laband syndrome (hereditary gingival fibromatosis) (Zimmermann-­ Laband syndrome) – autosomal dominant; soft, large floppy ears; bulbous soft nose, gingival fibromatosis; dysplastic/absent nails; atrophic distal phalanges (short terminal phalanges), hyperextensible metacarpophalangeal joints, hepatosplenomegaly, hypertrichosis, mental retardation Ped Derm 18:534–536, 2001; Ped Derm 10:263–266, 1993; J Otol Pathol Med 19:385–387, 1990; Oral Surg Oral Med Oral Pathol 17:339–351, 1964 Leprechaunism (Donohue syndrome) AD 117:531–535, 1981 Lipoid proteinosis J Oral Pathol Med 27:233–237, 1998 Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high pitched voice; mutation in RIN2 JAAD 66:842–851, 2012 Melkersson-Rosenthal syndrome (orofacial granulomatosis) AD 144:1627–1630, 2008 Menke's kinky hair disease – X-linked recessive; copper transport defect in young males J Clin Ped Dent 25:317–321, 2001 Mucopolysaccaridoses I-H JAAD 52:491–499, 2005 Multicentric reticulohistiocytosis – digital papule; knuckle pads; yellow papules and plaques AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968 Multiple endocrine neoplasia syndrome type I - gingival papules JAAD 42:939–969, 2000; angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia; mutation in menin, a nuclear protein involved in cell cycle regulation and proliferation JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004; AD 133:853–857, 1997 Neurofibromatosis – unilateral gingival enlargement J Clin Periodontol 27:361–365, 2000 Nevus sebaceus syndrome (Schimmelpenning-Feuerstein-Mims syndrome) – gingival hyperplasia, papillomas of tongue, thickened mucosa, anodontia, dysodontia JAAD 52:S62–64, 2005; Ped Derm 13:22–24, 1996; Int J Oral Maxillofac Surg 12:437–443, 1983 Pfeiffer’s syndrome JAAD 52:491–499, 2005

eruption, corneal opacities, mental retardation, aggressive behavior Ped Derm 18:534–536, 2001; Acta Paediatr Scand 55:233–238, 1966 Sturge-Weber syndrome Indian J Dent Res 9:140–144, 1998 Sweet’s syndrome Ann Hematol 81:397–398, 2002 Trichothiodystrophy syndromes - BIDS, IBIDS, PIBIDS – gingival hyperplasia, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Tuberous sclerosis – gingival fibromatosis JAAD 56:786–790, 2007; JAAD 52:491–499, 2005; BJD 135:1–5, 1996 Winchester syndrome – annular and serpiginous thickenings of skin; arthropathy, gargoyle-like face, gingival hypertrophy, macroglossia, osteolysis (multilayered symmetric restrictive banding), generalized hypertrichosis, very short stature, thickening and stiffness of skin with annular and serpiginous thickenings of skin, multiple subcutaneous nodules JAAD 50:S53–56, 2004; J Pediatr 84:701–709, 1974; Pediatrics 47:360–369, 1971

TRAUMA Epulis fissuratum – inflammatory fibrous hyperplasia due to ill-fitting dentures Irritation, chronic Mechanical trauma – ill-fitting dentures and implants Clin Oral Implants Res 12:179–187, 2001; ill-fitting scuba-diving mouthpiece Ned Tijdschr Tandheelkd 110:403–405, 2003 Mouth breathing - hyperplastic gingivitis

VASCULAR DISEASES Angiolymphoid hyperplasia with eosinophilia BJD 145:365, 2001 Granulomatosis with polyangiitis JAAD 77:795–806, 2017; J Clin Periodontol 19:64–66, 1992; AD 122:1435–1440, 1986; interdental gingival hyperplasia resembling strawberries AD 136:171–172, 2000

GINGIVITIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – methacrylate in dental restoration J Prosth Dent 90:225–227, 2003; acrylic crown Allergy 54:1316– 1321, 1999; gold Contact Dermatitis 28:276–281, 1993; chewing gum J Periodontol 42:709–712, 1971; cinnamic aldehyde Br Dent J 168:115–118, 1990; mints, dentifrices; desquamative gingivitis Contact Derm 39:90, 1998; Anti-laminin 332 mucous membrane pemphigoid – desquamative gingivitis BJD 169:100–105, 2013

Proteus syndrome AD 140:947–953, 2004; Int J Dermatol 42:826– 828, 2003

Bullous pemphigoid – periodontitis JAAD 76:975–978, 2017; desquamative gingivitis BJD 145:994–997, 2001; JAAD 7:729–735, 1982

Rutherfurd syndrome (gingival fibromatosis and corneal dystrophy) – autosomal dominant; gum hypertrophy, failure of tooth

Chronic granulomatous disease – acute gingivitis J Clin Periodontol 28:589–593, 2001

Gingivitis Chronic ulcerative stomatitis with epithelial antinuclear antibodies JAAD 77:795–806, 2017 Cicatricial pemphigoid (mucous membrane pemphigoid) – desquamative gingivitis; in adults and children AD 138:370–379, 2002; JAAD 43:571–591, 2000; J Periodontol 71:1620–1629, 2000; Semin Cutan Med Surg 16:308–313, 1997; Int J Paedeatr Dent 7:31–34, 1997 Complex aphthosis

451

DRUGS Cyclosporine Diltiazem DRESS syndrome - personal observation Nifedipine Oral contraceptives Phenytoin

Congenital neutropenia Cyclic neutropenia – oral aphthae, gingivitis, weakness, fever, sepsis, diarrhea, gangrenous enterocolitis Ped Derm 20:519–523, 2003; Ped Derm 18:426–432, 2001; Am J Med 61:849–861, 1976 Dermatitis herpetiformis - desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Dermatomyositis – telangiectatic gingivitis in childhood dermatomyositis Dialogues in Dermatology, Nov 2001; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Epidermolysis bullosa acquisita - desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997

EXOGENOUS AGENTS Chewing gum - desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Foreign body gingivitis Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83:562–570, 1997 Mouthwash - desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Tobacco – smoking

Good syndrome – adult acquired primary immunodeficiency in context of past or current thymoma; sinopulmonary infections; lichen planus, oral lichen planus of tongue, gingivitis, oral erosions BJD 172:774–777, 2015; Am J Med Genet 66:378–398, 1996

INFECTIONS

Graft vs host disease

AIDS – periodontitis, gingivitis linear gingival erythema Clin Oral Invest; Springer Verlag, 2008; Topics in HIV Medicine 13:143–148, 2006

Immunoglobulin deficiency with hyper IgM and neutopenia Infantile genetic agranulocytosis – subcutaneous abscesses Acta Paediatr Scand 64:362–368, 1975 Leukocyte adhesion deficiency syndrome (congenital deficiency of leucocyte-adherence glycoproteins) (CD11a(LFA-1), CD11b, CD11c, CD18)(CD 18 beta2 subunit) – necrotic cutaneous abscesses, gingivitis, progressive periodontitis and oral infections, septicemia, ulcerative stomatitis, pharyngitis, otitis, pneumonia, peritonitis NEJM 376:1141–1146, 2017; JAAD 60:289–298, 2009; Dermatol Therapy 18:176–183, 2005; JAAD 31:316–9, 1994; Periodontol 6:26–36, 1994; Pediatr Pathol 12:119–130, 1992; BJD 123:395–401, 1990; Pediatr Dent 12:107–111, 1990 Linear IgA disease – desquamative gingivitis JAAD 65:677–679, 2011; Aust NZ J Ophthalmol 27:443–446, 1999; Semin Cutan Med Surg 16:308–313, 1997; Oral Surg Oral Med Oral Pathol 70:450– 453, 1990 Lupus erythematosus - systemic lupus erythematosus – lesions of gums; red or purpuric areas with red halos break down to form shallow ulcers BJD 135:355–362, 1996; BJD 121:727–741, 1989; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Mixed connective tissue disease - desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Mucous membrane pemphigoid – desquamative gingivitis JAMADerm 152:1396–1398, 2016; Sem Cut Med Surg 34:171–177, 2015 Pemphigus vulgaris – periodontitis JAAD 76:975–978, 2017; Sem Cut Med Surg 34:171–177, 2015; J Periodont 70:808–812, 1999; J Periodontol 59:611–614, 1988; desquamative gingivitis JAAD 77:795–806, 2017; Semin Cutan Med Surg 16:308–313, 1997; pediatric pemphigus – desquamative gingivitis Ped Derm 36:730– 731, 2019 Rheumatoid arthritis – periodontal disease JAAD 77:795–806, 2017; Eur J Med Res 3:387–392, 1998 Sjogren’s syndrome – periodontal disease JAAD 79:736–745, 2018; JAAD 77:795–806, 2017

Abscesses – gingival, periodontal, peri-coronitis, peri-coronal, peri-­endodontic Prim Dent 6:46–51, 2017

Aspergillosis – invasive aspergillus stomatitis Clin Inf Dis 33:1975– 1980, 2001 Calymmatobacterium granulomatis (Donovanosis) J Clin Inf Dis 25:24–32, 1997 Candidiasis - desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Ebola virus hemorrhagic fever (Filovirus) – dark red discoloration of soft palate, pharyngitis, oral ulcers, glossitis, gingivitis; morbilliform exanthem which becomes purpuric with desquamation of palms and soles; high fever, body aches, myalgia, arthralgias, prostration, abdominal pain, watery diarrhea; disseminated intravascular coagulation Int J Dermatol 51:1037–1043, 2012; JAMA 287:2391– 2002; Int J Dermatol 51:1037–1043, 2012; JAAD 65:1213–1218, 2011; MMWR 44, No.19, 382, 1995 Epstein-Barr virus-associated hydroa vacciniforme – ulcerative gingivitis and aphthous stomatitis Eur J Dermatol 22:380–383, 2012 Gonorrhea – primary infection Herpes simplex - primary herpetic gingivostomatitis JAAD 57:737– 763, 2007; Infection 25:310–312, 1997 HIV gingivitis/periodontitis Oral Dis 3 Suppl 1:S141–148, 1997; linear gingival erythema of HIV Histoplasmosis – necrotizing gingivitis Int J Health Sci (Qassim)13:37–40, 2019; BJD 133:472–474, 1995 Leishmaniasis – New World leishmaniasis; nasal, oropharyngeal, gingival involvement Trop Doct 7:7–11, 1977; post kala-azar leishmaniasis Measles - personal observation Mycobacterium tuberculosis – periorificial tuberculosis; gingival tuberculosis J Contemp Dent Pract 14:137–139, 2013; Braz J Inf Dis 11:172–173, 2007 Myiasis gingiva J Periodontol 66:892–895, 1995 Nocardia asteroides – gingivitis with brain abscess Postgrad Med J 73:327–328, 1997

452 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Noma (cancrum oris) (necrotizing gingivitis) – Fusobacterium necrophorum, Prevotella intermedia, alpha-hemolytic streptococci, Actinomyces spp. J Oral Pathol Med 43:1–6, 2014Oral Dis 5:144–149,156–162, 1999 Paracoccidioidomycosis – granulomatous ulcerative gingivitis with loss of teeth JAAD 53:931–951, 2005; Cutis 40:214–216, 1987 Pseudomonas-induced necrotizing gingivostomatitis Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:644–645, 1999 Serratia marcescens Acta Ped Jpn 37:377–380, 1995 Staphylococcus hominis Streptococcal gingivitis J Contemp Dental Pract 5:150–157, 2004 Zika virus – fever, morbilliform (macular and papular exanthem), gingivitis with bleeding gums, arthralgia, conjunctivitis, myalgia, headache, retro-orbital pain, edema of hands and feet; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) JAAD 74:1286–1287, 2016; NEJM 360:2536–2543, 2009

INFILTRATIVE DISEASES Desquamative gingivitis JAAD 78:839–848,851–861, 2018   Allergic contact dermatitis   Behcet’s disease   Cicatricial pemphigoid   Complex aphthosis   Epidermolysis bullosa acquisita   Erythema multiforme   Graft vs host disease   Irritant contact dermatitis   Lichen planus   Paraneoplastic pemphigus   Pemphigus vulgaris Langerhans cell histiocytosis – destructive periodontitis which may simulate necrotizing gingivitis; “floating teeth”; gingival recession; may lead to severe alveolar bone loss J Periodontol 60:57–66, 1989 Plasma cell gingivitis - red plaque Cutis 69:41–45, 2002; JAAD 34:145–146, 1996; J Periodontol 55:235–241, 1984; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997

INFLAMMATORY DISEASES Acute gingivitis Acute necrotizing ulcerative gingivitis (ANUG) Ann Periodontol 4:65–73, 1999; J Periodont 66:990–998, 1995 Chronic marginal gingivitis J Clin Periodontol 13:345–359, 1986

  Juvenile periodontitis   Kindler’s syndrome   Langerhans cell histiocytosis  Leukemia   Olmsted syndrome   Papillon-Lefevre syndrome   Periodontal Ehlers-Danlos syndrome   Takahara's syndrome Kikuchi's histiocytic necrotizing lymphadenitis BJD 144:885–889, 2001 Orofacial granulomatosis – oral ulcers, aphthous ulcers, swollen lip(s), gingivitis, and/or gingival hypertrophy JAAD 62:611–620, 2010 Periodontal fistula Periodontitis, juvenile generalized Pyostomatitis vegetans - desquamative gingivitis; pustules with serpiginous ulcers JAAD 75:578–584, 2016; BJD 173:1556–1557, 2015; Semin Cutan Med Surg 16:308–313, 1997; red swollen gingiva with serpiginous white tracking; association with ulcerative colitis and Crohn’s disease An Bras Dermatol 86:S137–140, 2011; Med Oral Patol Oral Cir Bucal 14:E114–117, 2009; Clin Exp Dermatol 29:1–7, 2004 Sarcoidosis – red pebbled, mamillated gingival (“strawberry gums”) JAAD 77:809–830, 2017; JAAD 59:S118–120, 2008; Br Med J 296:1504, 1988; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997; gingival recession JAAD 77:809–830, 2017 Stevens-Johnson syndrome

METABOLIC DISEASES Agranulocytosis - periodontal destruction, gingival swelling Oral Surg Oral Med Oral Pathol 71:55–56, 1991 Calcinosis cutis – tumoral calcinosis with gingivitis Genetic Skin Disorders, Second Edition, 2010, pp.604–606 Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia (purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 167:988–900, 2012 Diabetes mellitus - severe periodontitis Diabetes Metab Syndr 8:255–258, 2014

Chronic ulcerative stomatitis – desquamative gingivitis BJD 143:671–672, 2000; JAAD 38:1005–1006, 1998; Semin Cutan Med Surg 16:308–313, 1997; JAAD 22:215–220, 1990

Hypoplasminogenemia – autosomal recessive; red eyes, oral ulcers, gingival edema; ligneous conjunctivitis with red eyes, ligneous periodontitis, blindness, tooth loss; decreased wound healing JAMADerm 150:1227–12228, 2014

Crohn’s disease Periodont Case Reports 11:20–22, 1989; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997

Kynureninase deficiency (xanthurenicaciduria)

Desquamative gingivitis Ann DV 127:381–387, 2000; Periodontol Insights 2:4–10, 1995

Neutropenic ulcers - personal observation

Erythema multiforme J Periodontol 64:910–913, 1993; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997 Gingivitis with premature loss of teeth Cutis 65:151–155, 2000  Acatalasia  Acrodynia   Chediak-Higashi syndrome   Congenital neutropenia   Cyclic neutropenia  Hypophosphatasia

Leukocyte defects - periodontitis Lupoid hepatitis Malnutrition Pellagra – gingivitis BJD 164:1188–1200, 2011 Plasminogen deficiency AD 150L1227–1228, 2014 Pregnancy Evidence Based Dent 14:107–108, 2013J Am Dent Assoc 110:365–368, 1985 Pubertal gingivitis BMJ Case Rep Aug 27, 2012 Renal failure, chronic Ren Fail 22:307–318, 2000

Gingivitis Scurvy - hemorrhagic gingivitis NEJM 379:282–289, 2018; NEJM 374:1369–1374, 2016; Ped Derm 28:444–446, 2011; JAAD 59:901–903, 2008; Cutis 66:39–44, 2000; JAAD 41:895–906, 1999; AD 120:1212–1214, 1984

453

Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) – periodontal disease JAAD 77:1194–1196, 2017; Int J Dent Hyg 8:68–74, 2010; Ped Derm 126:176–179, 2009

Kaposi’s sarcoma Postgrad Dent 2:93–100, 1992

Ehlers-Danlos syndrome (periodontal EDS) – type VIII; periodontitis, marked skin fragility, over shins, pretibial bruising, cigarette paper scars, atrophy, wrinkling, skin thin and translucent with visible venous pattern, marfanoid habitus with triangular face, long nose, thin philtrum; decrease types III and I collagen BJD 158:825–830, 2008; Ped Derm 24:189–191, 2007; Clin Pediatr 34:552–555, 1995; Clin Oral Investig 4:66–69, 2000; Birth Defects 13:85–93, 1983; JAAD 5:297–303, 1981

Leukemia - acute myelomonocytic leukemia AD 123:225–231, 1971;

Francois syndrome (dermochondrocorneal dystrophy) J Clin Periodontol 25:1047–1049, 1998

chronic lymphocytic leukemia, chronic myelogenous leukemia; periodontitis; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997

Haim-Munk syndrome – autosomal recessive; mutation in cathepsin C gene (like Papillon-Lefevre syndrome); palmoplantar keratoderma, scaly red patches on elbows, knees, forearms, shins, atrophic nails, prepubertal gingivitis with destruction of periodontium, onychogryphosis, arachnodactyly, recurrent pyogenic infections Ped Derm 30:749–750, 2013; BJD 152:353–356, 2005

Tumoral calcinosis J Clin Periodontol 16:643–646, 1989

NEOPLASTIC DISEASES Erythroplasia

Lymphoma – mimicking necrotizing and hyperplastic gingivostomatitis Eur J Dermatol 9:569–573, 1999 Metastases J Periodontol 85:132–139, 2014 Squamous cell carcinoma Waldenstrom’s macroglobulinemia

PARANEOPLASTIC DISORDERS Paraneoplastic pemphigus

PRIMARY CUTANEOUS DISEASES Epidermolysis bullosa, dominant dystrophic Ped Derm 34:166–171, 2017 Epidermolysis bullosa, recessive dystrophic EB, gravis (Hallopeau, Siemens variant) Epidermolysis Bullosa:Basic and Clinical Aspects. New York:Springer, 1992: 135–151 Hereditary PPK (Unna-Thost) with oral keratosis or periodontosis Rook p. 3055, 1998, Sixth Edition Lichen planus - desquamative gingivitis Sem Cut Med Surg 34:171–177, 2015; JAMA 312:1794–1795, 2014; in ulcerative lichen planus BJD 172:538–540, 2015; BJD 166:36–43, 2012; JAAD 46:207–214, 2002; Ann DV 127:381–387, 2000 (French); Semin Cutan Med Surg 16:308–313, 1997; vulvo-vaginal-gingival syndrome (erosive lichen planus) JAAD 55:98–113, 2006; Int J Derm 28:381–384, 1989; red gingiva Psoriasis – periodontitis and psoriasis BJD 172:282–285, 2015; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997

PSYCHOCUTANEOUS DISEASES Factitial gingivitis NY State Dent J 40:33–36, 1974; desquamative gingivitis Semin Cutan Med Surg 16:308–313, 1997

SYNDROMES Behcet’s disease Chediak-Higashi syndrome – gingivitis, periodontitis BJD 178:335– 349, 2018

Hereditary mucoepithelial dysplasia HOPP syndrome - hypotrichosis, striate, reticulated pitted palmoplantar keratoderma, acro-osteolysis, psoriasiform plaques, lingua plicata, onychogryphosis, ventricular arrhythmias, periodontitis BJD 150:1032–1033, 2004; BJD 147:575–581, 2002 Ichthyosis follicularis with atrichia and photophobia (IFAP) – beefy red gingiva; collodion membrane and erythema at birth; ichthyosis, spiny (keratotic) follicular papules (generalized follicular keratoses), non-­scarring alopecia, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis, photophobia; nail dystrophy, psychomotor delay, short stature; enamel dysplasia, beefy red tongue, angular stomatitis, atopy, lamellar scales, psoriasiform plaques, palmoplantar erythema Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; AD 125:103–106, 1989; Ped Derm 12:195, 1995; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999 Job’s syndrome (Hyper IgE with STAT3 mutation) KID syndrome with fissured lips – paronychial pustules, blepharitis without keratitis, perineal psoriasiform plaques, tongue erosions, honeycomb palmoplantar keratoderma; red gingivae; mutation in connexin 26 (N14K)GJB2 Kindler's syndrome - desquamative lesions of the gingivae; severe periodontal disease; gingivitis; poikiloderma, cigarette paper wrinkling of dorsal hands and feet, webbing of fingers, angular cheilitis, ectropion JAAD 67:1113–1127, 2012; JAMA 306:767– 768, 2011; BJD 160:1119–1122, 2009; BJD 160:233–242, 2009; BJD 159:1192–1196, 2008; BJD 158:1375–1377, 2008; Ped Derm 23:586–588, 2006; AD 142:620–624, 2006; Actas Dermosifiliogr 96:677–680, 2005; AD 140:939–944, 2004; Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:488–491, 1997; BJD 66:104– 111, 1954 Lazy leukocyte syndrome Quintessence Int 10:9–14, 1979 Lipoid proteinosis – gingival hyperplasia J Oral Pathol Med 27:233–237, 1998 Orofacial granulomatosis – facial edema with swelling of lips, cheeks, eyelids, forehead, mucosal tags, mucosal cobblestoning, gingivitis, oral aphthae BJD 143:1119–1121, 2000

Chronic familial neutropenia

Palmoplantar keratoderma, pes planus, onychogryphosis, periodontosis, arachnodactyly, and acroosteolysis BJD 115:243–248, 1986

Down’s syndrome J Periodontol 68:626–631, 1997; J Periodontol 53:158–162, 1982

Papillon-Lefevre syndrome – palmoplantar keratoderma and friable gingiva; rapid periodontal destruction with loss of deciduous and

454 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 permanent teeth Ped Derm 32:292–293, 2015; Ped Derm 30:749– 750, 2013; JAAD 60: 289–298, 2009; Quintessence Int 26:795–803, 1995; AD 124:533–539, 1988; Hum Genet 51:1–35, 1979; late onset Papillon-­Lefevre syndrome J Periodontol 64:379–386, 1993

Cryoglobulinemia type 1 – vasculitis, polyarthritis, and renal vasculitis Saudi M Kidney Dis Transpl 30:1470–1474, 2019

Schwachman-Diamond syndrome – periodontal disease and caries; abscesses, short stature, delayed puberty, skeletal changes, pancreatic exocrine deficiency, pancytopenias, failure to thrive, hepatomegaly, pneumonia, otitis media, osteomyelitis Ped Derm 28:568–569, 2011

DRESS – interstitial nephritis J Dermatol Dec 16, 2019

Sjogren-Larsson syndrome – caries, periodontitis, malocclusion, enamel hypoplasia JAAD 60:289–298, 2009; Swed Dent 7:141–151, 1983 Wiskott-Aldrich syndrome

TOXINS Acrodynia - mercury sensitivity - inorganic mercury poisoning JAAD 43:81–90, 2000; red gums AD 124:107–109, 1988

TRAUMA Denture wearer’s stomatitis – red sore gums and palate; candida, mechanical irritation, and bacteria in combination Scand J Dental Res82:151–190, 1974 Mouth breathing Physical trauma

VASCULAR DISEASES Cutaneous necrotizing eosinophilic vasculitis AD 130:1159–1166, 1994 Facial port wine stain – abnormal bleeding of gums JAAD 67:687– 693, 2012 Hemangiomas Granulomatosis with polyangiitis – strawberry gums JAAD 77:795– 806, 2017; NEJM 369:265–274, 2013; JAAD 48:311–340, 2003; JAAD 49:335–337, 2003; Ann Otol Rhinol Laryngol 107:439–445, 1998; AD 130:861–867, 1994; JAMA 246:2610–2611, 1981; Oral Surg Oral Med Oral Pathol 46:53–63, 1978

GLOMERULONEPHRITIS, CUTANEOUS MANIFESTATIONS Azathioprine hypersensitivity syndrome JAAD 65:184–191, 2011 Acquired partial lipodystrophy (progressive lipodystrophy, partial lipoatrophy, Barraquer-Simons syndrome) – gradual onset loss of subcutaneous fat from face, neck, trunk, and upper extremities in childhood, normal or increased fat of hips and lower extremities, proteinuria or mesangiocapillary glomerulonephritis, low C3 and presence of C3 nephritic factor, absence of insulin resistance; presence of other autoimmune diseases Cutis 70:65–69, 2002; J Clin Endocrinol Metab 85:1776–1782, 2000 Alport’s syndrome – gouty tophi, nephritis, deafnessabsent type IV collagen in skin; diagnosis by skin biopsy Mol Diagn 14:586–593, 2012 Cholesterol emboli

Cutis laxa with hypocomplementemia and nephrotic syndrome JAAD 46:128–130, 2002; AD 123:1211–1216, 1987 Eosinophilic granulomatosis with polyangiitis Fabry’s disease (alpha-galactosidase deficiency) – angiokeratomas, anhidrosis, hypohidrosis, acroparesthesias, cornea verticillata, heart failure JAAD 74:231–244, 2016 Granulomatosis with polyangiitis Ped Nephrology 32:2053–2056, 2017 Henoch-Schonlein purpura Heroin abuse, chronic skin popping, and renal amyloidosis J Nephropathol 2:196–200, 2013 Hypocomplementemic urticarial vasculitis J Korean Med Sci 32:2064–2068, 2017 Lepidopterism – black widow spider bite Leprosy – polyarthritis, dactylitis with erythema nodosum leprosum JAAD 71:795–803, 2014; JAAD 51:416–426, 2004; AD 138:1607– 1612, 2002; type 1 reaction demonstrates reappearance of resolved lesions, acute peripheral neuritis, edema of hands, feet, and face; type 2 reactions – erythema nodosum leprosum, with fever, malaise, arthritis, orchitis and/or glomerulonephritis; 70% of leprosy patients present with joint pain JAAD 57:914–917, 2007; leprous dactylitis Levamisole adulterated cocaine-induced vasculitis J Clin Rheumatol 25:e16–26, 2019 Mandibuloacral dysplasia – autosomal recessive; progeroid facies; facial asymmetry, micrognathia, small nose, prominent eyes, large open fontanelles; congenital brown pigmentation of ankles progresses to mottled pigmentation; hypoplastic clavicles; contractures of lower extremities; failure to thrive; progressive glomerulopathy; subcutaneous calcified nodules; mutation in ZMPSTE24 (lamin) JAMADerm 151:561–562, 2015 Methicillin-resistant Staphyloccus aureus skin infection and IgA nephropathy Medicine 95:e4023, 2016; post-infectious glomerulonephritis Human Pathol 42:279–284, 2011 Nail patella syndrome – triangular lunulae, absent of hypoplastic nails, absent or hypoplastic patellae, iliac horns, cloverleaf iris (Lester iris) Pflugers Arch 469:927–936, 2017 POEMS syndrome with immunotactoid glomerulopathy Medicine 97:e9920, 2018; Clin Nephrol 87:310–315, 2017 Psoriasis, erythrodermic – IgA nephropathy Medicine 98:e15433, 2019 Sarcoidosis – tubulointerstitial nephritis Saudi J Kidney Dis Transpl 30:1276–1284, 2019; Clin Nephrol 82:273–277, 2014 Systemic lupus erythematosus Rheumatic fever NEJM 369:75–80, 2013; JAAD 8:724–728, 1983 Scarlet fever Syphilis - secondary Infect Dis Clin North Amer 1:83–85, 1987; malignant lues Int J STDs and AIDS 23:599, 2012; Sex Trans Dis 36:512–514, 2009; nephrotic syndrome with membranous glomerulonephritis Vasculitis Infantile hemangioma JAMADerm 155:342–346, 2019 Port wine stain with gingival hypertrophy and dental abnormalities Ped Derm 33:570–584, 2016; J Craniofac surg 20:1629–1630, 2009 Facial port wine stain JAAD 67:687–693, 2012

Granulomas

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Microscopic polyangiitis Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94:707–711, 2002

Hypersensitivity pneumonitis (allergic bronchopulmonary aspergillosis; hot tub lung in setting of MAC infection)

Pyogenic granuloma

Idiopathic granulomatous mastitis Ann DV 146:571, 2019; with erythema nodosum J Eur Acad DV 31:e391–393, 2017; arthritis Rheumatol Int 31:1093–1095, 2011

Thrombocytopenia - hemorrhage Thrombocytopathy - hemorrhage

Idiopathic orofacial granulomatosis (Melkersson-Rosenthal syndrome, cheilitis granulomatosa of Miescher)

GRANULOMAS

Non-necrotizing epithelioid granulomas (sarcoid-like)

NONINFECTIOUS, NONNECROTIZING, NONCASEATING

Interstitial granulomatous dermatitis JAAD 45:286–291, 2001

BJD 178:335–349, 2018; Clin Rev Allergy Immunol 54:131–146, 2018; Ped Derm 27:285–289, 2010

Caseating granulomas (tuberculoid-like) Necrobiotic granulomas (NLD-like) Necrobiotic xanthogranuloma with paraproteinemia Primary biliary cirrhosis – hepatic granulomas Sarcoid

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Autoimmune hepatitis Chronic granulomatous disease BJD 178:335–349, 2018 Common variable immunodeficiency BJD 178:335–349, 2018 Lupus erythematosus MHC class I deficiency BJD 178:335–349, 2018 Rheumatoid arthritis Severe combined immunodeficiency Int J Derm 54:617–625, 2015

NEOPLASTIC DISEASES Carcinoid tumors Carcinomas – renal cell, breast, colon Kaposi’s sarcoma Exp Mol Pathol 87:89–93, 2009 Lymphomas – Hodgkin’s disease; non-Hodgkin’s lymphoma; granulomatous cutaneous T-cell lymphoma Seminomas

Wiskott-Aldrich syndrome

PRIMARY CUTANEOUS DISEASES

X-linked hypogammaglobulinemia BJD 178:335–349, 2018

Granuloma annulare

Unclassified combined immunodeficiency

Lupus miliaris disseminate faciei

X-linked hyper IgM syndrome

SYNDROMES DRUG REACTIONS

Ataxia telangiectasia BJD 178:335–349, 2018

Drug reaction – hepatic granulomas due to allopurinol, sulfonamides, quinidine, others Dermatol Clinics 33:525–539, 2015

Cartilage hair hypoplasia BJD 178:335–349, 2018 Nijmegen syndrome Omenn syndrome BJD 178:335–349, 2018

EXOGENOUS AGENTS Foreign body reactions – beryllium Acta Biomed 76Suppl2:11–14, 2005; silica, asbestos, talc crystals, sutures, splinters, etc.); zirconium, chromium, aluminum, beryyium, paraffin, vegetable oils, tattoo inks, injection of fillers

VASCULAR DISORDERS Churg-Strauss disease Giant cell arteritis (temporal arteritis) Granulomatosis with polyangiitis

INFECTIONS AND INFESTATIONS

Lymphomatoid granulomatosis Takayasu’s disease

Insect bites Sea urchins

INFILTRATIVE DISORDERS Langerhans cell histiocytosis; other histiocytoses

INFLAMMATORY DISORDERS Crohn’s disease AD 132:928–932, 1996 Erdheim-Chester disease

INFECTIOUS NON-NECROTIZING/NONCASEATING GRANULOMA Thorax 63:78–84, 2008; Clin Inf Dis 23:146–158, 1996; Int J Dermatol 23:585–597, 1984 Actinomycosis - necrotizing or non-necrotizing granulomas Aspergillosis – necrotizing (more often) or non-necrotizing granulomas Bartonella henselae Botryommycosis – Staphylococcus, Pseudomonas

456 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Brucellosis – hepatic granulomas Clin Gastroenterol Hepatol 5:1109–1112, 2007

Gingival hyperplasia (strawberry gingivitis) – red, friable, hyperplastic gingivae

Candidiasis

Granulomas of the ear or mouth

Cat scratch disease – Bartonella spp; necrotizing or non-necrotizing granulomas

Hemorrhagic bullae

Chromomycosis

Malignant pyoderma – preauricular large necrotic ulcers covered with fibrin, copious purulent secretion Tideskr Nor Laegeforen April 18, 2019; AD 98:58–76, 1968

Coccidioidomycosis - necrotizing or non-necrotizing granulomas Cryptococcosis – rarely caseating granulomas Med Mycol 41:177– 178, 2003

Livedo reticularis

Nasal crusting

Cytomegalovirus – granulomatous hepatitis

Nasal septal perforation

Epstein-Barr virus – granulomatous hepatitis

Necrotic ulcerations

Granuloma inguinale – Calymmatobacterium granulomatis

Oral ulcers Am J Dermatopathol 37:293–294, 2015

Hepatitis B, C

Palmar bullae

Histoplasmosis - necrotizing or non-necrotizing granulomas Arch Int Med 149:2421–2426, 1989

Palpable purpura (leukocytoclastic vasculitis) JAAD 31:605–612, 1994

HIV disease

Panniculitis and subcutaneous nodules

Leprosy (Mycobacterium leprae)

Papules or pustules of the extremities

Leishmaniasis Listeriosis

Pyoderma gangrenosum-like lesions Rheum Int 38:1139–1151, 2018; Ped Derm 34:e231–234, 2017

Lymphogranuloma venereum – Chlamydia granulomatis

Rheumatoid arthritis-like nodules

Mycobacterium chelonae

Saddle nose deformity

Mycobacterium marinum – swimming pool granuloma

Subungual digital infarcts resembling splinter hemorrhages

Mycobacterial infections – classically caseating granulomas, but may be non-caseating

Temporal arteritis Unilateral eyelid edema Caspian J Intern Med 10:343–346, 2019

Nocardia North American blastomycosis Paracoccidioides brasiliensis Pasturella multocida Pneumocystis - necrotizing or non-necrotizing granulomas Q fever - necrotizing or non-necrotizing granulomas Schistosomiasis

GREEN PIGMENTATION CONGENITAL LESIONS Mongolian spots - blue-green pigmentation Ped Derm 30:683–688, 2013

Sporothrix schenckii Syphilis - necrotizing or non-necrotizing granulomas Toxoplasmosis Tularemia - necrotizing or non-necrotizing granulomas Yersinia enterocolitica Whipple’s disease

GRANULOMATOSIS WITH POLYANGIITIS, CUTANEOUS MANIFESTATIONS

DRUG REACTIONS Drug eruption – morbilliform drug eruption in setting of hyperbilirubinemia Hydroxychloroquine – blue-green pigmentation of shins JAMA Derm 149:935–940, 2013; blue green lunulae

EXOGENOUS AGENTS

Acne fulminans Indian J DV Leprol July 11, 2019

Copper exposure; green hair, green seborrheic keratosis - from swimming pool - personal observation; glasses frame; green skin stain - copper in tap water Ped Derm 31:497–499, 2014; Cutis 77:39–41, 2006; green skin – copper bracelet - personal observation

Acne-like ulcers of face Inf Disord Drug Targets Nov 14, 2019

Blue hyperalimentation fluid in setting of jaundice

Acneiform red purple papules and pustules JAAD 72:659–667, 2015

Brilliant green (triphenylmethane dye) – green nails Cutis 105:317– 318, 2020

Conjunctivitis Ear chondritis Recurrent epistaxis Erythema nodosum-like lesions J Cut Pathol 34:739–747, 2007 Fingertip infarction

Green baby - due to intrauterine exposure to Evan's blue dye Am J Perinatol 5:234–235, 1988 Green foot syndrome – occlusive rubber soled basketball sneakers and hyperhidrosis Ped Derm 2:38–40, 1984; JAAD 69:E198–199, 2013

Green Pigmentation Krokodil (desomorphine) – intravenous drug abuse contaminated with paint thinner, lighter fluid, gasoline, lead, zinc, hydrochloric acid green scaly skin; gangrene down to bone leading to amputation Clin Inf Dis 61:1840–1849, 2015

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Kaposi’s sarcoma Cutis 88:14–16, 2011 Mongolian spots – blue-green pigmentation Ped Derm 30:683–688, 2013

Marvel comics Green Hulk AD 147:341, 2011 Textile dyes Clin in Derm 37:516–519, 2019

PRIMARY CUTANEOUS DISEASES

Tattoo Clin in Derm 37:516–519, 2019

Acquired dermal melanocytosis (acquired dermal melanocytic hamartoma) – blue-green patch of back JAAD 73:348–350, 2015

Tube feeding with FD and C blue No.1 JAMADerm 152:697, 2016; Critical Care Med 30:598–601, 2002

Apocrine chromhidrosis Clin in Derm 37:516–519, 2019

INFECTIONS AND INFESTATIONS

Eccrine chromhidrosis – green patchy hyperpigmentation JAMA Derm 149:1339–1340, 2013; Ann Int Med 145:710–711, 2006; JAAD 35:108–109, 1996; JAAD 26:655–656, 1992

Pseudomonas foot in atopic dermatitis Clin in Derm 37:516–519, 2019

Green chromonychia – pseudomonas

Pseudomonas interdigital web space infection Clin in Derm 37:516–519, 2019

METABOLIC DISORDERS Hyperbilirubinemia – green palms AD 146;209–210, 2010 Hyperbilirubinemia and morbilliform drug rash – personal observation

SYNDROMES Green cast syndrome Clin Exp Dermatol 34:e364–365, 2009 Wells’ syndrome in resolving phase Clin in Derm 37:516–519, 2019

Hypochromic anemia – chlorosis JAMA 257:2799–2800, 1987

TRAUMA

Jaundice and blue tube feeding - personal observation

Bruise Clin in Derm 37:516–519, 2019

Liver disease with biliverdin in skin Clin in Derm 37:516–519, 2019

NEOPLASTIC DISORDERS Chloroma (myeloid sarcoma) in acute myelogenous leukemia - Clin in Derm 37:516–519, 2019 Granulocytic sarcoma – violaceous nodule with green halo Cutis 94:65, 81–82, 2014

VASCULAR DISORDERS Hemorrhage – green ulcer - personal observation Superficial hemosiderotic lymphovascular malformation (hobnail hemangioma) (targetoid hemosiderotic hemangioma) – red-brown papule; blue-purple papule; yellow/green blue/papule Ped Derm 31:281–285, 2014

HAIR ABNORMALITIES

NEOPLASTIC DISORDERS Eruptive vellus hair cysts JAAD 72:890–900, 2015

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION

PRIMARY CUTANEOUS DISEASES

NEMO deficiency(X-chromosomal ectodermal dysplasia with immunodeficiency) BJD 178:335–349, 2018

Acquired progressive kinking of the hair Ped Derm 34:617–618, 2017

SCID type Schimke – fine hair BJD 178:335–349, 2018

Circle hairs JAAD 72:890–900, 2015

Trichodysplasia of immunosuppression (trichodysplasia spinulosa, viral-associated trichodysplasia spinulosa, pilomatrix dysplasia, cyclosporine-induced folliculodystrophy) JAAD 60:169–171, 2009; AD 142:1643–1648, 2006; JAAD 52:540–541, 2005; Am J Surg Pathol 29:241–246, 2005; JAAD 52:540, 2005; JAAD 50:318–322, 2004; JAAD 50:310–315, 2004; JAAD 43:118–122, 2000; J Invest Dermatol Symp Proc 4:268–271, 1999; Hautarzt 46:841–846, 1995

Ectopic hair of the glans BJD 153:218–219, 2005 Keratosis pilaris JAAD 72:890–900, 2015 Pili multigemini JAAD 72:890–900, 2015 Pili trianguli et canaliculi – kinky hair; uncombable hair syndrome; silvery blonde or straw-colored hair, frizzy and disorderly Ped Derm 37:534–536, 2020 Rolled hairs JAAD 72:890–900, 2015

DRUG REACTIONS

Trichostasis spinulosa JAAD 72:890–900, 2015

Anti-PD1 and anti-PD-L1 – hair repigmentation JAMADerm 153:1162–1165, 2017

Woolly hair (woolly hair hypotrichosis) – autosomal dominant, autosomal recessive BJD 173:865–866, 2015; JAAD 59:1–22, 2008; Q J Med 1:331–347, 1907; Trans St Johns Hosp Soc 60:160–177, 1974; symmetrical allotrichia (acquired progressive kinking) Cutis 24:322–324, 1979; woolly hair nevus JAAD 22:377–381, 1990; woolly hair seen in Noonan’s, cardiofaciocutaneous, Naxos, Carvajal, and skin fragility-woolly hair syndromes JAAD 61:813– 818, 2009

Carbidopa – darkening of hair Clin Exp Dermatol 14:317–318, 1989 Epidermal growth factor receptor inhibitors – cetuximab and panitumumab; erlotinib and gefitinib; lapatinib; canertinib; vandetanib – hirsutism, hair kinking JAAD 72:203–218, 2015 Erlotinib – hair repigmentation JAAD 77:902–910, 2017 Etretinate – darkening of hair JAAD 34:860, 1996

SYNDROMES

Gefitinib/erlotinib/cetuximab/panitumumab (epidermal growth factor receptor inhibitors) – hair changes JAAD 71:217–227, 2014

Cardio-facio-cutaneous syndrome(Noonan-like short stature syndrome) – autosomal dominant, acanthosis nigricans, xerosis/ ichthyosis, eczematous dermatitis, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, lentigines, nevi of palms and soles, keratosis pilaris, patchy or widespread ichthyosiform eruption, sparse curly short scalp hair and eyebrows and lashes, temporal alopecia, palmoplantar keratoderma of pressure points, hemangiomas, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects BJD 180:172–180, 2019; JAAD 46:161–183, 2002; Ped Derm 17:231–234, 2000; JAAD 28:815–819, 1993; AD 129:46–47, 1993; JAAD 22:920–922, 1990; port wine stain Clin Genet 42:206–209, 1992

Isotretinoin – curly hair Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015 PUVA - darkening of hair BJD 146:325–329, 2002 Tamoxifen – darkening of hair BJD 132:483–484, 1995 Verapamil – darkening of hair Lancet 338:1520, 1991

EXOGENOUS AGENTS Ingrown hairs

INFLAMMATORY DISORDERS Celiac disease - darkening of hair BJD 146:325–329, 2002

METABOLIC DISORDERS Kwashiorkor – yellow brittle hair, alopecia JAMADerm 150:910–911, 2014 Scurvy – corkscrew hairs Trichothiodystrophy – with ERCC2 mutation (excision repair) – matted twisted hair with ichthyosis; collodion baby, neutropenia and hypogammaglobulinemia, poor growth Ped Derm 36:668–671, 2019

Carvajal syndrome(ectodermal dysplasia/skin fragility syndrome) – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; woolly hair, generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; mutation in PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin Ped Derm 32:641–646, 2015; Ped Derm 32:102–108, 2015; BJD 166:36–45, 2012; Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Chediak-Higashi syndrome – silvery hair BJD 178:335–349, 2018 Costello syndrome – curly hair

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Hair Breakage 459 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral papules with hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; loss of function of PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin Ped Derm 36:255–257, 2019; BJD 166:36–45, 2012; Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Griscelli syndrome – silvery hair BJD 178:335–349, 2018; Am J Med 65:691–702, 1978

Pili torti   Bjornstad syndrome   Crandall syndrome   Menkes’ kinky hair syndrome   Ectodermal dysplasias  Neonatal ichthyosis sclerosing cholangitis syndrome (NISCH) – autosomal recessive; sparse scalp hair, lamellar ichthyosis, thin eyelashes and eyebrows; mutation in CLDN1 gene (claudin)(tight junction protein); teeth anomalies, mental retardation bilateral uveal synechiae BJD 170:976–978, 2014 Straight hair nevus of scalp Ped Derm 36:260–261, 2019 Woolly hair nevus, Blaschko-linear pigmentation, epidermal nevi; HRAS mutation Ped Derm 36:368–371, 2019

TRAUMA Electron beam - darkening of hair BJD 146:325–329, 2002

Hermansky-Pudlak syndrome – white hair BJD 178:335–349, 2018 Hunter’s syndrome (mucopolysaccharidosis type II) – fleshy ivory white papules and nodules (pebbling) in ridging or reticular pattern, symmetric, involving area between the angle of the scapula and anterior axillary line; coarse facial features, luxuriant scalp hair; bony abnormalities, recurrent umbilical and inguinal hernias; recurrent otitis media and pneumonia; developmental delay; coarse straight scalp hair; hypertrichosis of body and face; slate grey nevi; bilateral knee pain; decreased sulfoiduronate sulfatase (L-iduronate2-sulfatase) resulting in buildup of dermatan sulfate and heparin sulfate Ped Derm 37:369–370, 2020; Ped Derm 15:370–373, 1998 Kinky hair   Acquired progressive kinking of the hair   Bjornstad syndrome   Congenital pili torti syndrome  Etretinate Clin Exp Dermatol 10:426–431, 1985   Hereditary (familial)woolly hair syndrome   Ionizing radiation BJD 113:467–473, 1985  Isotretinoin Clin Exp Dermatol 15:143–145, 1990   Menkes’ kinky hair syndrome  Pseudomonilethrix  Trauma   Uncombable hair syndrome  Whisker hair – kinking of hair over periauricular areas of scalp which evolves into extensive baldness   Woolly hair nevus KLICK syndrome (keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; Acta DV 77:225–227, 1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989 Marie-Unna hereditary hypotrichosis – autosomal dominant; sparse curly hair; begins at puberty; at vertex; starts affects eyebrows, eyelashes, body and pubic hair; 50% with widely spaced incisors; 8p21 JAMADerm 150:567–568, 2014; Ped Derm 28:202–204, 2011; BJD 160:194–196, 2009; Ped Derm 19:250–252, 2002; Derm Wschr 82:1167–1178, 1925 Menkes' kinky hair syndrome - silvery hair, generalized hypopigmentation, lax skin of brows, neck, and thighs Cutis 90:170–172, 2012; JAAD 59:1–22, 2008; Ped Derm 15:137–139, 1998; carrier state with hypopigmented swirls and streaks; trichorrhexis nodosa Olsen, p.107, 1993 Netherton’s syndrome BJD 178:335–349, 2018

HAIR BREAKAGE AD 148:1051, 2012

AUTOIMMUNE DISEASES Alopecia areata

DEGENERATIVE DISORDERS Central centrifugal cicatricial alopecia

EXOGENOUS AGENTS Hair care products   Chemical relaxers or straighteners   Hair dyes   Permanents or curly perms   Styling products – gel, hair spray

INFECTIONS AND INFESTATIONS Syphilis Tinea capitis

METABOLIC DISORDERS Androgenetic alopecia Argininosuccinic aciduria Trichothiodystrophy (tiger tail appearance with polarized light

PRIMARY CUTANEOUS DISEASES Atopic dermatitis Monilethrix Pili annulati Pili torti-associated diseases (Bazex syndrome, Bjornstad syndrome, Crandall syndrome, Menkes syndrome, Rapp-Hodgkin syndrome Seborrheic dermatitis

460 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

PSYCHOCUTANEOUS DISORDERS Trichotillomania

SYNDROMES Netherton’s syndrome - trichorrhexis invaginata

TRAUMA

Pili multigemini   Cleidocranial dysostosis Woolly hair   Cardiofaciocutaneous syndrome   Carvajal syndrome   Ichthyosis, osteoma cutis, nail dystrophy   Keratois pilaris   Naxos syndrome   Noonan syndrome   Striate palmoplantar keratoderma

Braiding Excessive brushing or combing

HAIR BREAKAGE WITH NO HAIR FRAGILITY

Hair care practices

Ped Derm 33:481–487, 2016

Hair extensions

Trichorrhexis nodosa  Argininosuccinicaciduria  Citrullinemia  Hypothyroidism   Kabuki syndrome   Menkes’ kinky hair syndrome  Monilethrix   Trichohepatic enteric syndrome   Vitamin B7 deficiency

Heat styling – hot combs, blow dryer Trichorrhexis nodosa

HAIR BREAKAGE WITH HAIR FRAGILITY Ped Derm 33:473–480, 2016 Trichorrhexis nodosa  Argininosuccinicaciduria  Citrullinemia  Hypothyroidism   Kabuki syndrome   Menkes’ kinky hair syndrome  Monilethrix   Trichohepatic enteric syndrome   Vitamin B7 deficiency Monilethrix   Hereditary koilonychias   Holt-Oram syndrome   Keratosis pilaris Pili torti   Anorexia nervosa   Bazex-Dupre-Cristol syndrome   Bjornstad syndrome  Citrullinemia   Laron syndrome   Menkes’ kinky hair syndrome   Oral retinoids   Vitamin B7 deficiency Trichorrhexis invaginata  Atopy  Erythroderma   Netherton’s syndrome Trichothiodystrophy  Infections  PIBIDS  Pre-eclampsia   Xeroderma pigmentosum Pili annulati   Alopecia areata   Autoimmune thyroid disease   IgA deficiency Pili bifurcate   Cognitive defect   Dental abnormalities   Juvenile cataracts   Pseudomonilethrix type II   Trisomy 8   Ulcerative colitis

Monilethrix   Hereditary koilonychias   Holt-Oram syndrome   Keratosis pilaris Pili torti   Anorexia nervosa   Bazex-Dupre-Cristol syndrome   Bjornstad syndrome  Citrullinemia   Laron syndrome   Menkes’ kinky hair syndrome   Oral retinoids   Vitamin B7 deficiency Trichorrhexis invaginata  Atopy  Erythroderma   Netherton’s syndrome Trichothiodystrophy  Infections  PIBIDS  Pre-eclampsia   Xeroderma pigmentosum Pili annulati   Alopecia areata   Autoimmune thyroid disease   IgA deficiency Pili bifurcate   Cognitive defect   Dental abnormalities   Juvenile cataracts   Pseudomonilethrix type II   Trisomy 8   Ulcerative colitis Pili multigemini   Cleidocranial dysostosis Woolly hair   Cardiofaciocutaneous syndrome   Carvajal syndrome   Ichthyosis, osteoma cutis, nail dystrophy   Keratois pilaris   Naxos syndrome

Hair Shaft Nodules or Nits (Particulate Matter)   Noonan syndrome   Striate palmoplantar keratoderma Pili trianguli et canaliculi   Digital abnormalities   Epidermal nevi   Juvenile cataracts  Retinoids  Oligodontia   Phalango-epiphyseal dysplasia

461

NEOPLASTIC DISEASES Multiple myeloma - monoclonal protein with yellowish-white hair casts of eyelashes and scalp hair and cutaneous spicules of nose AD 142:1665–1666, 2006; JAAD 49:736–740, 2003

PRIMARY CUTANEOUS DISEASES Hair knots JAAD 47:415–418, 2002 Monilethrix JAAD 47:415–418, 2002

 AIR SHAFT NODULES OR NITS H (PARTICULATE MATTER)

Peripilar hair casts (pseudonits) Dermatologica 182:124–127, 1991; Cutis 43:380–381, 1989; AD 75:509–513, 1957 Seborrheic dermatitis JAAD 50:1–12, 2004 Tinea amientacea

EXOGENOUS AGENTS

Trichoptilosis JAAD 55:956–961, 2006

Glue Olsen, p.95, 1993

Trichorrhexis nodosa – congenital, acquired JAAD 16:1–24, 1987

Hair spray - pseudonits JAAD 36:260, 1997 Lacquer Olsen, p.95, 1993 Paint Olsen, p.95, 1993 Retained selenium sulfide shampoo

SYNDROMES Menkes’ kinky hair syndrome – trichorrhexis nodosa Olsen, p.107, 1993 Netherton's syndrome – trichorrhexis invaginata

INFECTIONS AND INFESTATIONS Black piedra (Piedraia hortae) – black hard nodules of scalp, beard, mustache, or pubic hair BJD 130 Suppl 43:26–28, 1994 Pediculosis capitis, pubis – nits of pubic hair, eyebrows, eyelashes Ped Derm 20:356–357, 2003; JAMA 250:32, 1983; beard, axillae, areolar hair, scalp hair along margins; truncal hair in hirsute men

HAIR, PREMATURE GRAYING DEGENERATIVE DISEASES Aging - hypopigmented hair

Psocid (Liposcelis) infestation JAAD 50:1–12, 2004 Tinea capitis Trichobacteriosis J Derm Case Rep 5:36–37, 2011; JAAD 55:956– 961, 2006 Trichomycosis – trichomycosis axillaris – yellow, red, or black concretions of hair shaft of axillary hair; Corynebacterium species J Drugs in Dermatol 10:1472–1473, 2011 AD 115:444–445, 1979; trichomycosis pubis Int J Derm 30:667–669, 1991 White piedra (trichosporosis) - Trichosporon cutaneum (formerly beigelii), T. ovoides, T. asahii, T. mucoides, T. ovoides, T. asteroides, T. inkin BJD 173:856–858, 2015; Clin Microbiol Rev 24:682–700, 2011; Cephalosporium acremonium, Brevibacterium mcbrellneri – soft white or light-brown nodules of beard, mustache, pubic; scalp less often JAAD 55:956–961, 2006; JAAD 49:746–749, 2003; JAAD 47:415–418, 2002; Cutis 70:209–211, 2002; Australas J Dermatol 32:75–79, 1991; BJD 123:355–363, 1990; Ann DV 114:819–827, 1987; JAAD 14:982–983, 1986; AD 118:208–211, 1982; Mem Inst Oswaldo Cruz 3:86–107, 1911; Cephalosporium acremonium Chin Med J 104:425–427, 1991

DRUGS Bleomycin - hypopigmented hair Cetuximab – hair hypopigmentation JAAD 77:902–910, 2017 Chloroquine - hypopigmentation of hair AD 121:1164–1166, 1985 Dasatinib – including hair hypopigmentation JAAD 77:902–910, 2017 Dixarazine – white hair Acta DV (Stockh) 61:85–88, 1981 Etretinate – lightening of hair JAAD 34:860, 1996 Fluorobutyrophenone – hypopigmented hair Haloperidol - hypopigmented hair Hydroxychloroquine - hypopigmented hair Hydroquinone – hypopigmentation of skin and hair Imatinib (tyrosine kinase inhibitor) NEJM 347:446–447, 2002 Mephenesin – hypopigmented lightening of hair Br Med J i:997– 998, 1963 Para-amino benzoic acid – hypopigmented hair

INFILTRATIVE DISEASES

Pazopanib – hair hypopigmentation JAAD 77:902–910, 2017

Langerhans cell histiocytosis

Phenobarbital – depigmentation of skin and hair Ann DV 119:927– 929, 1992 Phenols

METABOLIC DISEASES

Phenylthiourea – hypopigmentation of skin and hair

Argininosuccinicaciduria – trichorrhexis nodosa Ped Derm 24:25– 27, 2007

Regorafinib – hair hypopigmentation JAAD 77:902–910, 2017 Quinacrine – loss of hair pigmentation

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Sunitinib – interruption of hair color JAAD 77:902–910, 2017; AD 144:1525–1526, 2008; gray hair BJD 161:1045–1051, 2009

rufous, Hermansky-Pudlak syndrome – hypopigmented skin and hair JAAD 19:217–255, 1988

Triparanol – hypopigmented hair

Albinoidism JAAD 19:217–255, 1988

Valproic acid – hypopigmented hair

Alopecia areata – white (hair) overnight AD 102:162–167, 1970

METABOLIC DISEASES

Canities   Diffuse hypomelanosis of scalp hair   Book syndrome  Chronic protein loss or deficiency (kwashiorkor, renal disease, inflammatory bowel disease, malabsorption)   Down’s syndrome   Fanconi syndrome   Hallerman-Streiff syndrome  Hyperthyroidism   Prolidase deficiency   Treacher-Collins syndrome   Vitamin B12 deficiency

Acrodermatitis enteropathica with anorexia nervosa – hypopigmented hair JAMA 288:2655–2656, 2002

Vitiligo

INFECTIONS AIDS – premature canities

INFLAMMATORY DISEASES Post-inflammatory hypopigmentation of skin and hair

Celiac disease

Poliosis White forelock - isolated finding

Copper deficiency - hypopigmented hair Essential fatty acid deficiency Histidinemia - hypopigmented hair Homocystinuria – lightening of hair Hyperthyroidism Hypothyroidism Iron deficiency anemia (segmented heterochromia)(canities segmentata sideropaenica) - hypopigmented hair AD 125:531–535, 1989

SYNDROMES Angelman syndrome Ataxia telangiectasia JAAD 42:939–969, 2000; AD 134:1145–1150, 1998; JAAD 10:431–438, 1984 Book’s syndrome – autosomal dominant; premature graying, premolar hypodontia, palmoplantar hyperhidrosis Am J Hum Genet 2:240–245, 1950 Branchio-oculo-facial syndrome Am J Med Genet 27:943–951, 1987

Kwashiorkor - hypochromotrichia and hypopigmentation of skin Cutis 67:321–327, 2001; Cutis 51:445–446, 1993

Chediak-Higashi syndrome – autosomal recessive Curr Prob Dermatol 18:93–100, 1989

Malnutrition - flag sign

Cri du chat syndrome (chromosome 5, short arm deletion syndrome) – premature greying of the hair, pre-auricular skin tag with low-set malformed ears J Pediatr 102:528–533, 1983; J Pediatrics 77:782–791, 1970

Oasthouse disease – white hair, recurrent edema; increased serum methionine Panhypopituitarism – pale, yellow tinged skin Pellagra – leukonychia Pernicious anemia – vitiligo, canities BJD 82:221–226, 1970 Phenylketonuria – phenylalanine hydroxylase deficiency; fair skin and hair; lichen sclerosus-like changes JAAD 49:S190–192, 2003

Cross syndrome – autosomal recessive; gingival fibromatosis, microphthalmia with cloudy corneas, mental retardation, spasticity, growth retardation, athetosis, hypopigmentation, silvery gray hair Ped Derm 18:534–536, 2001; J Pediatr 70:398–406, 1967

Vitamin B12 deficiency No To Shinkei 49:283–286, 1997(Japanese)

Down’s syndrome – hypopigmented hair; vitiligo; canities Ped Derm 24:317–320, 2007

Prolidase deficiency J Inherited Met Dis 31:814, 2007; JAAD 29:818–821, 1993

Dyskeratosis congenita JAAD 77:1194–1196, 2017

Renal disease – hypopigmented hair Tyrosinemia - hypopigmented hair Vitamin B12 deficiency (pernicious anemia) – white hair AD 122:896–904, 1986; premature canities Eur J Dermatol 17:551– 552, 2007; Cutis 71:127–130, 2003 Zinc deficiency

NEOPLASTIC DISEASES Melanoma – leukoderma; hypopigmented hair

PRIMARY CUTANEOUS DISEASES Albinism – tyrosinase negative(type IA), yellow mutant (type IB), platinum, tyrosinase positive (type II), minimal pigment, brown,

Elejalde syndrome (neuroectodermal lysosomal disease) – autosomal recessive; silvery hair, profound central nervous system dysfunction, normal immune function, photo-hyperpigmentation (bronze coloration) Ped Derm 21:479–482, 2004; AD 135:182–186, 1999 Fanconi’s syndrome - hypopigmented hair Fisch’s syndrome - hypopigmented hair; impaired hearing; partial heterochromia iridis Clin Genetics 60:301–394, 2001; J Med Genet 3:656–665, 1997 Griscelli syndrome (partial albinism with immunodeficiency) – rare and fatal immunologic disorder characterized by partial oculocutaneous albinism, silver gray sheen of the hair (microscopic examination of hair shafts demonstrated large pigment granules accumulated in the medullary region), and variable cellular and immunodeficiency. Between the ages of 4 months and 4 years patients experience recurrent disease - exacerbation of lymphohistiocytic infiltration of multiple organs, including the brain and meninges often triggered by infection J Ped 125:886, 1994

Heart Block and Rash 463 Hallerman-Streiff syndrome - hypopigmented hair Hereditary premature canities Hermansky-Pudlak syndrome – white skin and hair AD 135:774– 780, 1999 Hypomelia, hypotrichosis, facial hemangioma syndrome (pseudothalidomide syndrome) – sparse silvery blond hair Am J Dis Child 123:602–606, 1972 Lipoatrophy (distal), stunted growth, muscle cramps, and hypoplastic uterus Rinsho Shinkeigaku 23:867–873, 1983

Tay syndrome – autosomal recessive, growth retardation, triangular face, cirrhosis, trident hands, premature canities, vitiligo Tietz’s syndrome – autosomal dominant; congenital sensorineural hearing loss, global hypopigmentation, premature graying of hair (canities), diffuse speckling of sun-exposed areas Treacher-Collins syndrome - hypopigmented hair Unusual facies, vitiligo, canities, progressive spastic paraplegia Am J Med Genet 9:351–357, 1981 Vogt-Koyanagi-Harada syndrome Ann DV 127:282–284, 2000

Matzner syndrome Harefuah 96:104–105, 1979

Waardenburg syndrome Ped Derm 36:72–84, 2019

Menkes’ kinky hair syndrome – hypopigmented hair

Werner’s syndrome (pangeria) – graying of temples in teenage years progressing to canities Medicine 45:177–221, 1966

Mukamel syndrome – autosomal recessive; premature graying in infancy, lentigines, depigmented macules, mental retardation, spastic paraparesis, microcephaly, scoliosis Myotonic dystrophy - premature canities with hypopigmented hair; myotonia, muscle wasting, cataracts Occipital white lock of hair

TRAUMA Physical trauma - hypopigmented hair Radiation therapy – hypopigmented hair

Neurofibromatosis – localized hypopigmented hair Palmoplantar keratoderma, large ears, sparse hypopigmented scalp hair, frontal bossing Ped Derm 19:224–228, 2002 Piebaldism Pierre-Robin syndrome - hypopigmented hair Prader-Willi syndrome Premature canities, palmoplantar hyperhidrosis, premolar hypodontia American J Human Genetics 2:240–263, 1950 Progeria (Hutchinson-Gilford syndrome) - hypopigmented hair canities and premature canities Cutis 89:161–163, 2012 Pseudocleft of upper lip, cleft lip-palate, and hemangiomatous branchial cleft – canities Plast Reconstr Surg 83:143–147, 1989 Pseudocleft of the upper lip (or cleft lip/palate), linear cutaneous lesions on the lateral neck (ranging from bronchial clefts to epidermal nevi) and cervical thymus Am J Med Genet 27:943–951, 1987 Robert’s syndrome(hypomelia-hypotrichosis-facial hemangioma syndrome) – autosomal recessive; mid-facial port wine stain extending from forehead to nose and philtrum, cleft lip +/- cleft palate, sparse silver-blond hair, limb reduction malformation, characteristic facies, malformed ears with hypoplastic lobules, marked growth retardation Clin Genet 31:170–177, 1987; Clin Genet 5:1–16, 1974 Rothmund-Thomson syndrome - hypopigmented hair; poikiloderma, photosensitivity, alopecia, cataracts, short stature Eur J Hum Genet 17:151–158, 2009 Seckel’s syndrome (bird-headed dwarfism) – autosomal recessive; hair sparse and prematurely gray, growth retardation, beak-like nose, large eyes, skeletal defects Am J Med Genet 12:7–21, 1982

HEART BLOCK AND RASH  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSFUNCTION Dermatomyositis Br Heart J 56:479–482, 1986; Arch Intern Med 144:2185–2189, 1984; trifascicular block Chest 71:413–416, 1977 Lupus erythematosus - neonatal lupus erythematosus Am Coll Cardiol 31:1658–1666, 1998; Rheum Dis Clin North Amer 20:119– 127, 1994; adult onset systemic lupus erythematosus with myocarditis Scleroderma Clin Dermatol 12:267–275, 1994; Acta Cardiol 37:31–38, 1982; G Ital Cardiol 11:132–138, 1981(Italian); Sem Hop 44:489–496, 1968(French)

DRUG REACTIONS Carbamazepine – heart block, sensorineural hearing loss Arch Otolaryngol Head Neck Surg 125:225–227, 1999 Chloroquine – third degree heart block Rev Rhum Engl Ed 65:58–62, 1998 Digitalis – acute digitalis poisoning Bull Mem Soc Med Hop Paris 119:247–274, 1968(French) Diltiazem Am J Cardiol 54:477–491, 1984 Doxycycline – chronic intoxication with Wenckebach block, hepatic, renal, hematopoietic toxicity J Intern Med 246:591–592, 1999

Sialic acid storage disease – silver hair, coarse facial features, hepatosplenomegaly AD 135:203–208, 1999

Drazoxolon Food Cosmet Toxicol 7:481–491, 1969

Silvery hair JAAD 58:S115–116, 2008   Chediak-Higashi syndrome – giant granules   Elejalde syndrome  Griscelli’s syndrome – hepatosplenomegaly, hemophagocytic lymphohistiocytosis, neurologic symptoms, clumped melanin granules within hair shaft

Immune checkpoint inhibitors – combination of ipilimumab and nivolumab NEJM 375:1749–1755, 2016

Sensory neurodeafness with premature graying of the hair Laryngol Otol 73:355–367, 1959 Sudden whitening of hair overnight – vitiligo, telogen effluvium, alopecia areata, psychogenic causes Int J Dermatol 55:362–364, 2016; Clin Exp Dermatol 37:458–459, 2012

DRESS

Penicillin – fever, arthralgia, urticarial; second degree block, atypical Wenckebach block Isr J Med Sci 14:848–851, 1978 Practolol Eur J Clin Pharmacol 12:167–170, 1977

EXOGENOUS AGENTS Cocaine Am J Med Case Rep Dec 14, 2017 Malathion poisoning Arch Environ Health 21:533–541, 1970

464 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFECTIOUS DISEASES

NEOPLASTIC DISEASES

Bacterial endocarditis BMJ Case Rep Marh 20, 2019

Lymphoma - non-Hodgkin’s lymphoma – metastatic lymphoma to heart or primary cardiac lymphoma Arch Mal Coeur Vaiss 93:1333– 13338, 2000; primary cardiac B-cell lymphoma Eur Med J Cardiovascular Imaging 19:552, 2018

Chagas’ disease Bull Pan Am Health Organ 26:47–59, 1992 Coxsackie virus Presse Med 15:1105, 1986(French) Dengue hemorrhagic fever – Mobitz type 1 second degree block Korean Circ J 46:861–869, 2016; Southeast Asian J Trop Med Public Health 31:642–645, 2000 Diphtheria, cutaneous – heel ulcerations, bullae; fatal heart block Ped Cardiol 21:282–283, 2000; J Med Assoc Thai 56:670–674, 1973 Herpes simplex virus – complete heart block Zhongua Min Guo Xiao Er Ke Yi Zue Hui Za Zhi 38:381–384, 1997

Cardiac metastases

PRIMARY CUTANEOUS DISEASES Unilateral lentiginosis with blue nevi BJD 130:390–393, 1994

Lyme disease (Borrelia burgdorferi) – first degree heart block, Wenckebach, or congenital heart block J Am Coll Cardiol 73:717, 726, 2019; Inf Dis NA 29:255–268, 2015; Cardiology 87:76–78, 1996; Res Microbiol 146:329–340, 1995; Br Heart J 70:88–90, 1993; Glas Srp Akad Nauka (Med)43:237–239, 1993(SerboCroatian-Cyrillic); Annu Rev Med 43:93–103, 1992; Pacing Clin Electrophysiol 15:252–255, 1992; Wis Med J 90:632–634, 1991; Del Med J 63:13–17, 1991; Cesk Pediatr 45:276–278, 1990(Czech); Klin Wochenschr 68:431–435, 1990; Arch Mal Coeur Vaiss 79:1251– 255, 1986(French); Postgrad Med 77:303–308,310, 1985; Ann Cardiol Angeiol 33:395–399, 1984(French);

SYNDROMES

Meningococcemia – myocarditis with focal necrosis of conduction system and complete heart block J R Army Med Corps 141:169– 171, 1995; Ann Emerg Med 12 :391–393, 1983

Multiple lentigines syndrome(LEOPARD) Ann Dermatol Venereol 112:59–62, 1985(French); AD 259–262, 1973(Feb)

Acrocephalosyndactyly, cardiac disease, defects of ear, skin, and lower limbs J Pediatr 79:104–109, 1971 Ehlers-Danlos syndrome – complete heart block Guys Hosp Rep 120:355–364, 1971 Generalized congenital fibromatosis – complete heart block J Radiol Electrol Med Nucl 58:465–469, 1977(French) Kawasaki’s disease J Thoracic Dis 10:E108–112, 2018 Lipoid proteinosis

Mucormycosis – post-operative intramyocardial abscess Ann Thorac Surg 58:1760–1762, 1994

Neurofibromatosis type 1 – bilateral bundle branch block Med Clin 77:258–259, 1981(Barcelona); Am J Roentgenol Radium Ther Nucl Med 122:146–149, 1974

Rheumatic fever Pediatr Dermatol 16:288–291, 1999; Pacing Clin Electrophysiol 21:2025–2028, 1998

Pseudoxanthoma elasticum Histopathology 4:607–611, 1980

Rubella – bifascicular block Staphylococcus aureus toxic shock syndrome J Pediatr 117:89–92, 1990; Am J Dis Child 144:748–750, 1990 Syphilis – syphilitic aneurysm with conduction defect Arq Bras Cardiol 52:341–344, 1989(Portuguese) Varicella – varicella myocarditis Kokyu To Junkan 40:499–503, 1992(Japanese)

Reactive arthritis Ann Rheum Dis 47:1017, 1020, 1988; Ugeskr Laeger 150:2748–2749, 1988(Danish); Arch Mal Coeur Vaiss 72:799–805, 1979(Danish)

TRAUMA Blunt trauma Heart Rhythm 14:1561–1569, 2017 Radiation, therapeutic – to left chest Chest 71:231–234, 1977

Halophilic Vibrio sepsis – hemorrhagic bullae; complete heart block South Med J 73:1285–1287, 1980

VASCULAR DISORDERS INFILTRATIVE DISORDERS

Allergic granulomatous Angiitis Zhonghua Nei Ke Za Zhi 32:685– 687, 1993(Chinese)

Amyloidosis Rev Esp Cardiol 52:1157–1158, 1999 Systemic mastocytosis – pleural effusion; myo-pericardial infiltration; atrio-ventricular block Arch Mal Coeur Vaiss 74:215–221, 1981(French)

INFLAMMATORY DISEASES Sarcoidosis – myocardial conduction system granulomas causing heart block AD 136:712–714, 2000; Eur J Dermatol 246:591–592, 1999; Nihon Kyobu Shikkan Gassai Zashi 33:1111–1118, 1995

 EART FAILURE, CUTANEOUS H MANIFESTATIONS See also CARDIAC DISEASE AND CUTANEOUS MANIFESTATIONS

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION

METABOLIC DISORDERS

Adult onset Still’s disease

Primary oxalosis JAAD 22:952–956, 1990; Acta Pathol Jpn 30:451–458, 1980; Med J Aust 1(23):873–874, 1976

Macrophage activation syndrome Rev Paul Pediatr 37:252–256, 2019

Heliotrope 465

DRUG REACTIONS Adalimumab Expert Opinion Drug Saf 4:637–641, 2005 Hypersensitivity myocarditis, drug induced (amoxicillin) Korean J Int Med 29:236–240, 2014 DRESS syndrome Eosinophilic myocarditis

INFECTIONS AND INFESTATIONS

18:534–536, 2001Horner’s syndrome, including congenital Horner’s syndrome – ptosis, miosis, anhidrosis; contralateral unilateral facial flushing JAAD 55:193–208, 2006; J Neurol Neurosurg Psychiatry 53:85–86; Harlequin sign – hemifacial flushing and contralateral hypohidrosis in Horner’s syndrome Ped Derm 23:358–360, 2006 Hunter’s syndrome (mucopolysaccharidosis IIb) - X-linked recessive; scapular papules; cobblestoned skin colored papules also of posterior axillary lines, upper arms, forearms, chest, outer thighs; decreased sulfoiduronate sulfatase;

Parvovirus B19

skin colored papules overlying scapulae; linear and reticular patterns; also on shoulder, upper arms and chest, and lateral thighs; rough thickened skin, coarse scalp hair, and hirsutism; coarse facies with frontal bossing, hypertelorism, and thick tongue; dysostosis multiplex; hunched shoulders and characteristic posturing; hepatosplenomegaly; upper respiratory infections due to laryngeal or tracheal stenosis; mental retardation; deafness; retinal degeneration and corneal clouding; umbilical and inguinal hernias; thickened heart valves lead to congestive heart failure; iduronate-2-sulfatase deficiency BJD 159:249–250, 2008; BJD 148:1173–1178, 2003; Clin Exp Dermatol 24:179–182, 1999; AD 134:108–109, 1998; JAAD 39:1013–1015, 1998; Ped Derm 15:370–373, 1998; Am J Med Genet 47:456–457, 1993; Ped Derm 7:150–152, 1990

Strongyloides hyperinfection J Parasit Dis 43:167–175, 2019

Kawasaki’s disease Open Med (Wars)15:8–13, 2019

Babesiosis Bacterial endocarditis BMJ Case Rep Jan 25, 2013 Black widow spider bite Case Rep Cardiol 2015:768089 Chagas’ disease (Trypanosoma cruzi) Corynebacterium diphtheriae Coxsackie virus A, B Ehrlichiosis Enterovirus Lyme disease

INFILTRATIVE DISORDERS Amyloidosis

INFLAMMATORY DISORDERS Sarcoidosis

METABOLIC DISORDERS Congestive heart failure - red nails, lunulae right sided congestive heart failure – peripheral edema Am J Med 113:580–586, 2002; Fabry’s disease – male, angiokeratomas, anhidrosis or hypohidrosis, orthostatic hypotension, stroke, renal insufficiency, verticillata cornea Hemochromatosis Int J Cardiol 244:226–228, 2017 Hyperthyroidism – high output heart failure; unilateral eyelid edema JAAD 48:617–619, 2003; hyperpigmentation of eyelids (Jellinek’s sign) JAAD 47:438, 2002; BJD 76:126–139, 1964; Graves disease – proptosis due to retraction of eyelids Kwashiorkor Pediatr 66:972–976, 1980

Multicentric reticulohistiocytosis Rev Med Interne 23:779–783, 2002

VASCULAR LESIONS Arteriovenous fistula (between iliac artery and vein) - right heart failure – edema of lower extremities with erythema (venous congestion) NEJM 367:2241–2247, 2012 Parkes-Weber syndrome – arteriovenous malformation with multiple arteriovenous fistulae along extremity with limb (usually leg) overgrowth; arteriovenous shunting; cutaneous red stain; lymphedema; high output congestive heart failure, hypertrophied digits with severe deformity; red foot JAAD 56:541–564, 2007; Curr Prob in Dermatol 13:249–300, 2002; BJD 19:231–235, 1907

HELIOTROPE AUTOIMMUNE DISORDERS Adult onset Still’s disease AD 148:947–952, 2012 Dermatomyositis – juvenile, amyopathic, paraneoplastic, connective tissue disease Lupus erythematosus, systemic BJD 143:679–680, 2000

NEOPLASTIC DISORDERS Castleman’s disease, multicentric J Rheum 20:1588–1591, 1993 Lymphoma – intravascular B-cell lymphoma Eur Heart J Case Rep Feb2, 2019

DRUGS Atorvastatin – anti-3-hydroxy-3methylglutaryl coenzyme reductase antibody (anti-HMGCR) positive necrotizing myopathy with dermatomyositis-­like eruption Muscle Nerve 57:e135–136, 2018 Bleomycin

SYNDROMES

Drug eruption – personal observation

Borrone dermatocardioskeletal syndrome – autosomal recessive or X-linked; gingival hypertrophy, coarse facies, late eruption of teeth, loss of teeth, thick skin, acne conglobata, osteolysis, large joint flexion contractures, short stature, brachydactyly, camptodactyly, mitral valve prolapse, congestive heart failure Ped Derm

Hydroxyurea Dermatol Online J 20 August 2017 Imatinib Int J Dermatol 45:1249–1251, 2006 Nivolumab-associated dermatomyositis Intern Med 57:2217–2221, 2018

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INFECTIONS Lyme disease Cureus 10:e2608, 2018 Toxoplasmosis

INFLAMMATORY DISEASES Sarcoid Neurology 30:1118–1121, 1980

HEMATOLOGIC MALIGNANCIES, CUTANEOUS SIGNS Int J Dermatol 45:14–22, 2006

NEUTROPHILIC DERMATOSES Sweet’s syndrome JAAD 69:557–564, 2013   Acute myelogenous leukemia  Histiocytoid Sweet’s syndrome JAMADerm 153:651–659, 2017; Medicine (Balt)95(15):e3033, April 2016; JAAD 70:1021–1027, 2014   Non-Hodgkin’s lymphoma   Myelodysplastic syndrome Pyoderma gangrenosum/bullous pyoderma gangrenosum An Bras Dermatol 93:133–134, 2018; Int J Dermatol 56:386–391, 2017  Acute myelogenous leukemia Leukemia Lymphoma 47:147–150, 2006   Multiple myeloma Clin Exp Dermatol 44:e13–15, 2019 Subcorneal pustular dermatosis of Sneddon and Wilkinson  Multiple myeloma BJD 172L296–298, 2015; Clin Exp Dermatol 34:46–48, 2009; Clin Exp Dermatol 33:229–233, 2008   Non-Hodgkin’s lymphoma Dermatol Onlin J Aug 15, 2008   Monoclonal gammopathy(often IgA type)

VESICULOBULLOUS DISORDERS Pemphigus vulgaris JAAD 78:1084–1089, 2018   Hodgkin’s disease   Non-Hodgkin’s lymphoma  Chronic lymphocytic leukemia – episodic papulovesicular eruption Dermatol Online J Sept 15, 2011 Pemphigus foliaceus   Hodgkin’s disease   Non-Hodgkin’s lymphoma   Chronic lymphocytic leukemia Paraneoplastic pemphigus JAAD 80:1544–1549, 2019; BJD 173:1442–1452, 2015   Angioimmunoblastic T-cell lymphoma Acta DV 94:235–236, 2014   Castleman’s disease Indian J Dermatol 59:4–21, 2014   Chronic lymphocytic leukemia J Med Case Rep 31:252, 2018   Hodgkin’s disease  Non-Hodgkin’s lymphoma Ann Hematol 94:683–685, 2015; Eur J Dermatol 21:122–124, 2011 Bullous pemphigoid  Non-Hodgkin’s lymphoma Clin Exp Dermatol 44:728–731, 2019; Dermatology 188:177–181, 1994 Dermatitis herpetiformis   Non-Hodgkin’s lymphoma

Linear IgA disease bullous dermatosis   Enteropathy-associated T-cell lymphoma   Hodgkin’s disease J Dermatol 17:633–637, 1990   Non-Hodgkin’s lymphoma   Multiple myeloma

REACTIVE ERYTHEMAS Erythroderma and exfoliative dermatitis JAAD 35:53–57, 1996  Acute lymphocytic leukemia Am J Dermatopathol 37:650–657, 2015   Acute myelogenous leukemia JAAD Case Rep 12:121–123, 2019  Chronic myelogenous leukemia Indian J DV Leprol 77:208–210, 2011   Myelodysplastic syndrome   Hodgkin’s disease   Non-Hodgkin’s lymphoma Erythema gyratum repens   B-cell lymphoma Indian J Dermatol 64:338, 2019   Essential thrombocythemia Acta DV 83:133–134, 20013   Hodgkin’s disease Med Cutan Ibero Lat Am 11:286, 1983   Myeloproliferative disease (acute myelogenous leukemia)   Diffuse large cell B-cell lymphoma Erythromelalgia   Myeloproliferative disease  Essential thrombocythemia Leukemia Lymphoma 58:715–717, 2017; Arch Int Med 149:150–159, 1989  Polycythemia vera Leukemia Lymphoma 58:715–717, 2017; Arch Int Med 149:150–159, 1989

PAPULOSQUAMOUS DISORDERS Acquired ichthyosis J College Physicians Surgeons Pakistan 21:40–42, 2011   Multiple myeloma Ann DV 113:829–832, 1986   Hodgkin’s disease Fortschr Med 93:1493–1496, 1975   Non-Hodgkin’s lymphoma Ann DV 128:31–34, 2001  Leukemia JAAD 40:862–865, 1999; HTLV-1(acute T-cell leukemia)( adult T-cell lymphoma/leukemia) JAAD 49:979–1000, 2003; JAAD 46:S137–141, 2002  Lymphoma - Hodgkin's disease – ichthyosis vulgaris-like changes of legs or generalized (increased G-CSF levels) JAAD 49:772– 773, 2003; Br Med J 1:763–764, 1955; non-Hodgkin's lymphoma, reticulolymphosarcoma, cutaneous T- cell lymphoma (CTCL) BJD 161:115–120, 2009; JAAD 34:887–889, 1996; B-cell lymphomas JAAD 40:862–865, 1999; CD 30+ cutaneous anaplastic large cell lymphoma BJD 161:115–120, 2009; JAAD 42:914–920, 2000; Tumori 85:71–74, 1999 Acanthosis nigricans   Multiple myeloma   Non-Hodgkin’s lymphoma Dermatomyositis   Multiple myeloma   Non-Hodgkin’s lymphoma Vasculitis  Acute myelomonocytic, myelogenous leukemia Int J Rhrum Dis 12:70–73, 2009; AML large vessel vasculitis J Med Case Rep 11:71 March 16, 2017  Chronic lymphocytic leukemia – granulomatous vasculitis Dermatol Online J 18:12 March 15, 2012   Chronic myelogenous leukemia

Hemihypertrophy (Asymmetric Overgrowth Syndromes)

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 Hairy cell leukemia Am J Hematol 94:1433–1434, 2019; BMJ Case Rep Oct 19, 2012  Large granular lymphocytic leukemia Semin Arthr Rheum 43:362–366, 2013   Multiple myeloma J Eur Acad DV 18:731–735, 2004   Myelodysplastic syndrome J Hematol 7:158–162, 2018   Non-Hodgkin’s lymphoma

Constitutional mismatch repair-deficiency (CMMR-D)syndrome – lentigines and café au lait macules; childhood and adulthood development of leukemias, lymphomas, brain tumors, colonic polyposis with cancer NEJM 370:2229–2236, 2014

Cronkhite-Canada syndrome Am J Med 77:555–557, 1984

Cutis laxa – heavy chain disease J Dermatol 45:1211–1215, 2018; JAMADerm 150:1192–1196, 2014; JAAD 59:S99–101, 2008

DERMAL DEPOSITION DISEASES Amyloidosis AL   Multiple myeloma Follicular mucinosis JAAD 80:1704–1711, 2019   Adult T-cell lymphoma/leukemia   Cutaneous peripheral T-cell lymphoma  Cutaneous T-cell lymphoma; folliculotropic CTCL; CD 4+ small/ medium CTCL   Primary cutaneous CD 30+ lymphoproliferative disorder Metastatic calcinosis – indurated papules, plaques, and nodules BJD 142:820–822,   Multiple myeloma Scleredema adultorum Clin Exp Dermatol 13:271–274, 1988   Multiple myeloma Multiple juvenile xanthogranulomas, neurofibromatosis type 1 – juvenile myelomonocytic leukemia Ped Derm 32:e29–32, 2015

HYPERPIGMENTATION Addisonian hyperpigmentation  Metastatic multiple myeloma (plasmacytoma) J Drugs Dermtol 14:1485–1486, 2015; J Coll Physicians Surg Pak 21:40–42, 2011; Dermatol Online J Sept 15, 2008 Fanconi’s syndrome(pancytopenia with congenital defects) – generalized olive-brown hyperpigmentation, especially of lower trunk, flexures, and neck with depigmented macules (rain drop-like); hypoplastic anemia, slender build, short broad thumbs, tapered fingers, microcephaly, hypogonadism Semin Hematol 4:233–240, 1967 POEMS syndrome  Multiple myeloma Curr Hematol Malig Rep 12:85–95, 2017; Hematol Clin NA 32:141–151, 2018; Semin Oncol 43:395–400, 2016

SUBCUTANEOUS VIOLACEOUS NODULES Multiple myeloma – truncal nodules, rarely face or extremities BMJ Case Rep Oct 5, 2015; JAAD 62:1076–1078, 2010

Cutaneous granulomas associated with leukemia/myelodysplastic disease Actas Dermosifiliogr 107:e27–32, 2016; Am J Dermatopathol 35:e26–29, 2013; AD 147:331–335, 2011

Dyskeratosis congenita – myelodysplastic syndrome, bone marrow failure JAAD 77:1194–1196, 2017; J Blood Med 5:157–167, 2014; Br J Haematol 145:164–172, 2009; Semin Cut Med Surg 16:72–80, 1997 Eosinophilic dermatosis of hematologic malignancy Am J Dermatopathol 41:303–308, 2019; Dermatol Online J 2014, Jan 15:20(1):21256 Epstein-Barr virus-associated hydroa vacciniforme-like T-cell lymphoma Br J Haematol 186:802, 2019; Diagn Pathol 14:82, 2019; J Cutan Pathol 43:1102–1111, 2016 Fingertip hypertrophy – chronic lymphocytic leukemia, leukemia cutis J Cutan Med Surg 7:57–60, 2003 GATA2 deficiency Granuloma annulare-like eruption – associated with B-cell chronic lymphocytic leukemia J Cutan Pathol 39:996–1103, 2012 Granulomatous rosacea – mimicked by B-cell lymphoma Dermatol Onlin J 2013 Oct 16:19(10):2033; AD 148:824–831, 2012 Klinefelter’s syndrome Langerhans cell histiocytosis with myelodysplasia, follicular lymphoma Am J Dermatopathol 40:588–53, 2018; BJD 167:1287– 1294, 2012; J Cutan Patho 33:171–174, 2006 Lymphomatoid papulosis and secondary lymphoma Leuk Lymphoma 56:1303–1307, 2015 Necrobiotic xanthogranuloma with paraproteinemia – monoclonal gammopathy, multiple myeloma Case Rep Ophthalmol 9:70–75, 2018 Neurofibromatosis, juvenile xanthogranulomas, and juvenile myelomonocytic leukemia Ped Derm 36:114–118, 2017 Pruritus without rash BJD 178:34–60, 2018 Schnitzler’s syndrome - 45% develop hematologic malignancy JAAD 67:1289–1295, 2012 Scleroderma Autoimmune Rev 16:461–468, 2017 Wiskott-Aldrich syndrome

HEMIHYPERTROPHY (ASYMMETRIC OVERGROWTH SYNDROMES) JAAD 48:161–179, 2003 Associated with:

FOLLICULAR SPICULES Multiple myeloma JAAD 19:879–890, 1988

CONGENITAL ABNORMALITIES Genitourinary malformations

OTHER DISORDERS Ataxia telangiectasia Blastic plasmacytoid dendritic cell neoplasm of skin – myelodysplastic syndrome Dermatol Online J Dec 16, 2014 Bloom’s syndrome

EXOGENOUS AGENTS Podoconiosis – multilobulated hyperkeratotic nodules of feet with hemihypertrophy; bare feet exposed to red clay from alkaline volcanic rock JAAD 65:214–215, 2011

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INFLAMMATORY DISORDERS Charcot foot JAAD 70:1–18, 2014

METABOLIC DISORDERS Hypothyroid myxedema masquerading as lymphedema Plastic Reconstr Surg Glob Open 31e457, 2015 Primary osteoma cutis – generalized osteomas; unilateral anodontia, hemihypertrophy, linear basal cell nevus

NEOPLASTIC DISORDERS Adrenocortical tumors Brain tumors Congenital melanocytic nevus – limb hypertrophy JAAD 67:495– 511, 2012 Connective tissue nevi Dermatofibrosarcoma protuberans – of the sole Dermatology 192:280–282, 1996 Fibrosarcoma, including congenital fibrosarcoma Ped Derm 14:241–243, 1997 Hepatoblastomas Wilms’ tumor

mutation Clin Genetics 91:14–21, 2017; JAAD 68:885–896, 2013; Am J Hum Genet 90:1108–1115, 2012; Ped Derm 27:311–312, 2010; Am J Med Genet 143A:2944–2958, 2007 Cowden’s disease - type 2 segmental Cowden’s disease – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi (including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of limbs, ballooning of toes, bowel polyps, glomerulosclerosis, macrocephaly BJD 156:1089–1090, 2007; Eur J Dermatol 17:133–136, 2007 Encephalocraniocutaneous lipomatosis syndrome – cranial asymmetry; lipomas, connective tissue nevi Cutis 80: 297–302, 2007 Fibrous dysplasia – one or multiple bones (McCune-Albright syndrome) of the entire skeleton J Pediatr Genetics 4:136–145, 2015 Hemihyperplasia multiple lipomatosis syndrome (familial lipomatosis/hemihyperplasia syndrome) – hemihyperplasia at birth, moderate overgrowth with subcutaneous lipomas, superficial capillary malformations JAAD 56:541–564, 2007; Cutis 80: 297–302, 2007; Overgrowth Syndromes. New York. Oxford Univ. Press, 2002, pp. 5–110; Am J Med Genet 79:311–318, 1998 HHML - increased risk for intra-abdominal embryonal malignancies, including Wilms’ tumor, adrenal cell carcinoma, hepatoblastoma Am J Med Genet 79:274–278, 1998 Juvenile hyaline fibromatosis AD 121:1062–1063, 1985; AD 107:574–579, 1973

PRIMARY CUTANEOUS DISEASES

Macrodystrophia lipomatosa – localized gigantism; unilateral limb involvement J Clin Imaging Sci Feb 27, 2019

Hypertrichosis

Malan syndrome J Pediatr Genetics 4:136–143, 2015

Isolated hemihypertrophy Cutis 83:255–261, 2009

Maffucci’s syndrome Cutis 83:255–261, 2009 Marshall-Smith syndrome J Pediatr Genetics 4:136–143, 2015

SYNDROMES AKT1 somatic mosaicism – hemihypertrophy, hemimacroglossia, epidermal nevus, café au lait macules BJD 175:612–614, 2016 Bannayan-Riley-Ruvalcaba syndrome J Ped Genetics 4:136–143, 2015 Beckwith-Wiedemann syndrome (hemihypertrophy-lipomatosis syndrome) – congenital overgrowth syndrome; abdominal wall defects, macroglossia, gigantism, glabellar nevus simplex, exomphalos, macroglossia, hypoglycemia, pre- and post-natal overgrowth, limb hemihypertrophy, embryonal cancers JAAD 74:231–244, 2016; JAAD 69:589–594, 2013; Cutis 80: 297–302, 2007; Am J Med Genet 79:274–278, 1998; Clin Genet 46:168–174, 1994 Bockenheimer’s syndrome (genuine diffuse phlebectasia of Bockenheimer) – extensive venous malformation Ped Derm 23:294–297, 2006 CHILD syndrome - verruciform xanthoma; giant red plaque of lateral foot; cobblestoned, verrucous giant tumor; enlarged foot; exophytic mass; X-linked dominant; mutation in NSDHL (NAD(P)-dependent steroid dehydrogenaselike gene) Cutis 88:269–272, 2012; Ped Derm 27:551–553, 2010; Ped Derm 15:360–366, 1998 CLOVE syndrome(congenital lipomatous overgrowth vascular malformations, epidermal nevi, spinal, skeletal abnormalities and scoliosis) – capillary, venous, and mixed vascular malformations, epidermal nevi, congenital lipomatous overgrowth; hemihypertrophy (milder than that of Proteus syndrome); ballooning of big toes, splaying of feet; symmetrically overgrown feet; wrinkling of palms and soles; severe central nervous system involvement; PIK5CA

Neurofibromatosis Cutis 80: 297–302, 2007 Nevus sebaceus syndrome – facial hemihypertrophy; hemimegalencephaly; neuronal and glial proliferation leading to enlargement of the cerebral hemisphere Ped Derm 24:428–429, 2007 Perlman syndrome J Pediatr Genetics 4:136–143, 2015 Phakomatosis pigmentokeratotica – coexistence of an organoid nevus and a checkerboard papular speckled lentiginous nevus; organoid nevus associated with hypophosphatemic vitamin D-resistant rickets JAAD 55:S16–20, 2006 PIK3CA/AKT/mTOR-related overgrowth syndromes – reticulated port wine stain; hemihypertrophy Ped Derm 33:536–542, 2016; GeneReviews.http://ncbi.nlm.nih.gov/pubmed/23946963; Am J Med Genet 167:287–295, 2015; JAAD 69:589–594, 2013; Nature Genetics 44:934–940, 2012   CLOVES syndrome   Fibroadipose hyperplasia  Macrocephaly capillary malformation syndrome (macrocephaly cutis marmorata telangiectatica congenita)(megalencephaly capillary malformation syndrome)   Proteus syndrome   Type 1 congenital macrodactyly Primrose syndrome – enlarge calcified ears; distal muscle wasting, diabetes, deafness, basal ganglia calcification Mol Syndromol 9:70–82, 2018 Proteus syndrome – soft tissue and bony hypertrophy of hands and feet, hemihypertrophy, exostosis, cranial hyperostosis, visceral hamartomas, lipomas, vascular anomalies, port wine stains, linear epidermal nevi, connective tissue nevus, gigantism, mosaic distribution of lesions; cerebriform thickening of palms and soles,

Herpetiform Lesions capillary, venous, lymphatic and combined slow-flow malformations (like Klippel-Trenaunay syndrome); lipohypoplasia; mosaic distribution, progressive course, sporadic occurrence; bilateral ovarian cystadenomas, parotid monomorphic adenoma, lipomas, vascular malformations, lung cysts, facial phenotype; somatic mosaic mutation of AKT1 NEJM 365:611–619, 2011; Cutis 83:255–261, 2009; JAAD 56:541–564, 2007; Cutis 80: 297–302, 2007; Eur J Pediatr 140:5–12, 1983; Birth Defects 15:291–296, 1979 PTEN-hamartoma-tumor syndrome – grossly enlarged hand; recurrent arteriovenous malformations of hand and forearm; macrocephaly, frontal bossing, café au lait macules, congenital nevi, low set ears, downward slanting eyebrows and palpebral fissures Ped Derm 28:466–467, 2011 Simpson-Golabi-Behmel syndrome – generalized somatic overgrowth; cardiac abnormalities in 36–47% J Pediatr Genetics 4:136–143, 2015; Cutis 83:255–261, 2009 SOLAMEN syndrome (segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus)(type 2 segmental Cowden’s syndrome) - segmental overgrowth, lipomatosis, arteriovenous malformation, epidermal nevus; loss of wild type PTEN allele in Cowden families; phenotype mimics Proteus patients Eur J Hum Genet 15:767–773, 2007 Sotos syndrome – generalized somatic overgrowth Cutis 83:255– 261, 2009 Tattan-Brown-Rahman syndrome Mol Syndromol 9:70–82, 2018 Tuberous sclerosis – hemihypertrophy, vascular anomalies, lymphedema Ped Derm 33:536–542, 2016; macrodactyly Ped Derm 18:364–365, 2001 Weaver syndrome - generalized somatic overgrowth Cutis 83:255– 261, 2009

VASCULAR LESIONS Arteriovenous malformations Capillary-venous malformation with phlebectasia of the lower limb – hemihypertrophy with small well defined blotchy blue patches amid prominent leg veins; prominent veins of popliteal fossa, knee, and dorsal foot Ped Derm 30:541–548, 2013; of arm with phlebectasias Ped Derm 32:287–289, 2015 Diffuse capillary malformation with overgrowth – reticulated red patch with hemihypertrophy (non-progressive proportionate overgrowth) JAAD 69:589–594, 2013 Facial port wine stain – maxillary and gingival hyperplasia JAAD 67:687–693, 2012 Hemangiomas, infantile Ped Derm 28:502–506, 2011; JAAD 56:541–564, 2007 Kaposiform hemangioendothelioma JAAD 56:541–564, 2007 Klippel-Trenaunaysyndrome(capillary-lymphatic-venous malformation) – varicose veins with or without venous malformations; port wine stain; hemihypertrophy (limb hypertrophy)(bony or soft tissue hyperplasia); may involve spleen, liver, bladder, colon JAAD 66:71–77, 2012; AD 146:1347–1352, 2010; JAAD 61:621–628, 2009; JAAD 56:541–564, 2007; JAAD 56:242–249, 2007; Arch Gen Med (Paris) 3:641–672, 1900 Lymphatic malformations – with skeletal hypertrophy JAAD 65:893–906, 2011 Macrocephaly-CMTC (cutis marmorata telangiectatica congenita syndrome) – renamed “macrocephaly-capillary malformation syndrome” - macrocephalic neonatal hypotonia and developmental delay; frontal bossing, segmental overgrowth, syndactyly, polydac-

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tyly, asymmetry, joint hypermobility, distended linear and serpiginous abdominal wall veins, patchy reticulated vascular stain without atrophy; telangiectasias of face and ears; midline reticulated facial nevus flammeus (capillary malformation)(vascular stains), hydrocephalus, skin and joint hypermobility, hyperelastic skin, thickened subcutaneous tissue, polydactyly, 2-3 toe syndactyly, post-axial polydactyly, hydrocephalus, frontal bossing, hemihypertrophy with segmental overgrowth; neonatal hypotonia, developmental delay; PIK3CA mutation BJD 175:810–814, 2016; JAAD 63:805–814, 2010; Ped Derm 26:342–346, 2009; AD 145:287–293, 2009; JAAD 58:697–702, 2008; Ped Derm 24:555–556, 2007; JAAD 56:541– 564, 2007; Ped Derm 16:235–237, 1999; Genet Couns 9:245–253, 1998; Am J Med Genet 70:67–73, 1997; Clin Dysmorphol 6:291– 302, 1997; (Note: Beckwith-Wiedemann syndrome demonstrates dysmorphic ears, macroglossia, body asymmetry, midfacial vascular stains, visceromegaly with omphalocele, neonatal hypoglycemia, BUT NO MACROCEPHALY) Parkes-Weber syndrome – arteriovenous malformation with multiple arteriovenous fistulae along extremity with limb (usually leg) overgrowth; arteriovenous shunting; cutaneous red stain; lymphedema; high output congestive heart failure, hypertrophied digits with severe deformity; red foot JAAD 56:541–564, 2007; hypertrophy with pulasatile dilated veins and arteries, palpable thrill, giant arteriovenous malformation NEJM 371:2114, 2014 PHACES syndrome – multilobulated giant hemangioma with hemihypertrophy of face Port wine stain JAMADerm 150:1336–1340, 2014 Reticular infantile hemangioma – refractory punctate and scattered ulcerations of buttocks, and/or perineum, involve legs of females, enlarged foot and limb; associated with ventral-caudal anomalies such as omphalocele, femoral artery hypoplasia, imperforate anus, solitary or duplicate kidney, tethered cord; congestive heart failure Ped Derm 24:356–362, 2007 Spindle cell hemangioendothelioma – multiple subcutaneous nodules; palmar giant cobblestoning; hypertrophy of hand Cutis 79:125–128, 2007 Stewart-Bluefarb syndrome – arteriovenous malformation of leg with multiple fistulae and port wine stain-like purplish lesions (Mali’s acroangiodermatitis/pseudo-Kaposi’s sarcoma) – brown macules, purple nodules and plaques, edema, varicose veins, hypertrichosis, cutaneous ulcers, enlarged limb JAAD 65:893–906, 2011 Sturge-Weber syndrome – facial capillary malformation (port wine stain), glaucoma, central nervous system leptomeningeal angiomatosis, bone +/- soft tissue overgrowth Current Problems Pediatric Adolescent Health Care 45:118–131, 2015 Tufted angioma JAAD 56:541–564, 2007 Vascular (venous) malformations JAAD 56:541–564, 2007; AD 139:1409–1416, 2003; enlarged hand, hemihypertrophy, mountain range changes BJD 157:558–562, 2007

HERPETIFORM LESIONS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis Brunsting-Perry cicatricial pemphigoid – herpetiform plaques with scarring Lancet 381:320–332, 2013; J Dermatol 38:887–892, 2011; AD 75:489–501, 1957

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Bullous pemphigoid Przegl Dermatol 69:291–294, 1982(Polish); vesicular pemphigoid JAAD 49:722–724, 2003; anti-p200 bullous pemphigoid – clustered vesicles JAMADerm 152:897–904, 2016

Protothecosis JAAD 32:758–764, 1995; Dermatol Clin 21:249–255, 2003; Int J Derm 25:54–55, 1986

Dermatitis herpetiformis

Syphilis – chancre Clin Dermatol 23:555–564, 2005

Epidermolysis bullosa acquisita BJD 131:898–900, 1994

Tinea corporis Hautarzt 40:364–389, 1989

Sand flea bites - personal observation

IgA pemphigus foliaceus JAAD 24:839–844, 1991 Linear IgA disease, adulthood or childhood - targetoid, urticarial, herpetiform lesions, confluent bullae BJD 177:212–222, 2017; Dermatol Online J Aug 15, 2017 Linear IgA/IgG bullous dermatosis – dyshidrosiform bullae of palms, herpetiform bullae, cutaneous erosions, tongue erosions JAMA Derm 149:1308–1313, 2013 Lupus erythematosus – bullous herpetiform variant JAAD 9:163, 1983; AD 115:1427–1428, 1979 Pemphigoid gestationis – herpetiform blisters BJD 172:120–129, 2015 Pemphigus(pemphigus herpetiformis) – annular array of bullae BJD 180:187–192, 2019; An Bras Dermatol 87:933–935, 2012; AD 135:943–947, 1999; BJD 141:754–755, 1999; including druginduced herpetiform pemphigus – thiopronine BJD 130:238–240, 1994; D-penicillamine J Dermatol 7:425–429, 1980; pemphigus foliaceus BJD 86:99–101, 1972; IgG/IgA pemphigus – herpetiform, targetoid lesions BJD 147:1012–1017, 2002; pemphigus with anti-desmoglein 3 IgG autoantibodies J Dermatol 31:407–410, 2004; pemphigus herpetiformis – annular arcuate red plaques with edematous borders with erosions and vesicles; concentric targetoid lesions; herpetiform blisters; serpiginous blisters BJD 171:1588– 1590, 2014; JAAD 70:780–787, 2014; Ped Derm 30:760–762, 2013; BJD 169:719–721, 2013; AD 148:531–536, 2012; AD 135:943–947, 1999

INFLAMMATORY DISEASES Erythema multiforme – herpetiform eruption Acta DV 62:141–146, 1982 Pyoderma gangrenosum BJD 157:1235–1239, 2007

NEOPLASTIC DISEASES Agminated fibroblastic connective tissue nevus – brown herpetiform nodules Ped Derm 36:997–998, 2019 Apocrine hidrocystomas BJD 176:488–490, 2017 Digital myxoid cyst - herpetiform appearance Ann Dermatol 22:194–195, 2010 Lymphatic malformation – circumscribed JAMA 321:1213–1214, 2019 Lymphomatoid papulosis – clustering of lesions JAAD 62:353–356, 2010; JAAD 57:1005–1011, 2007 Metastases – J Clin Pathol 59:1331–1333, 2006; ovarian adenocarcinoma Arch Gynecol Obstet 244:63–67, 1988

PARANEOPLASTIC DISEASES Paraneoplastic herpetiform dermatosis An Bras Dermatol 45:153– 160, 1970

EXOGENOUS AGENTS Acute iododerma from radiocontrast material - personal observation

PRIMARY CUTANEOUS DISEASES

Clamming dermatitis - personal observation

Acrodermatitis continua of Hallopeau

INFECTIONS AND INFESTATIONS

Aphthous ulcers, herpetiform Am J Otolaryngol 21:389–393, 2000; Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:141–147, 1996; J Mich Dent Assoc 66:357–363, 1984

Cowpox

Atopic dermatitis - periorbital crusting in atopic dermatitis due to group A beta hemolytic streptococcus; herpetiform lesions Ped Derm 28:230–234, 2011

Cryptococcosis JAAD 26:122–14, 1992; BJD 121:665–667, 1989; JAAD 10:387–390, 1984

Dermatitis herpetiformis-like spongiotic dermatitis - personal observation

Gonococcal paronychia

Dowling-Meara epidermolysis bullosa simplex (epidermolysis bullosa herpetiformis) – keratin 5 mutation JID 109:815–816, 1997; Arch Dermatol Res 286:233–241, 1994; JAAD 28(pt2)859–861, 1993; BJD 126:421–430, 1992; AD 122:190–198, 1986

Coxsackie A virus – herpetiform herpangina Virologie 35:49–53, 1984

Hand, foot, and mouth disease - personal observation Herpangina - personal observation Herpes simplex infections, including primary, recurrent, chronic herpes simplex, and eczema herpeticum (Kaposi’s varicelliform eruption)  With primary immunodeficiency syndromes BJD 178:335–349, 2018   DOCK-8 deficiency BJD 178:335–349, 2018   Growth retardation, adrenal insufficiency, T-lymphocyte defects (idiopathic CD4+ lymphopenia, IL2 deficiency, IL2R mutations) BJD 178:335–349, 2018   MCM4 deficiency BJD 178:335–349, 2018 Herpes zoster Histoplasmosis

Dyshidrosis Grover’s disease Impetigo herpetiformis Clin Dermatol 29:509–510, 2011 Nummular dermatitis Clin Dermatol 29:509–510, 2011 Psoriasis – herpetiform follicular papules JAMADerm 152:1043– 1044, 2016 Pustular psoriasis (Hebra’s herpetiform impetigo) Vestn Dermatol Venereol 1:63–65, 1990(Russian) Seborrheic dermatitis – herpetiform napkin dermatitis BJD 114:746–747, 1986 Urticaria

Heterochromia Iridum (IRIDIS)

VASCULAR DISEASES Acute hemorrhagic edema of infancy Henoch-Schonlein purpura - personal observation Granulomatosis with polyangiitis – herpetiform necrotic purpuric papules over joints (ankles, elbows) AD 148:849–854, 2012 Urticarial vasculitis

HETEROCHROMIA IRIDUM (IRIDIS) CONGENITAL Chediak-Higashi syndrome Congenital Horner’s syndrome Fisch’s syndrome - hypopigmented hair; impaired hearing; partial heterochromia iridis Clin Genetics 60:301–394, 2001; J Med Genet 3:656–665, 1997 Hirschsprung’s disease Hypomelanosis of Ito Can J Neurol Sci 15:124–129, 1988;

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Hypochromic heterochromia  Anemia   Coloboma or microcornea  Diabetic rubiosis iridis – neovascularization (rubeosis iridis or hyperemia of iris)   Glaucoma cyclitis crisis (Posner-Schlossman syndrome)   Horner’s syndrome Br J Ophthalmol 82:1095, 1998  Idiopathic   Iris atrophy  Iritis or iridocyclitis due to localized or generalized disease like tuberculosis, rheumatoid arthritis, syphilis, herpes zoster, sarcoidosis, herpes simplex infection, Fuchs heterochromic iridocyclitis Ophthalmologica 209:289–291, 1995   Ischemic neovascularization   Infiltration of iris by non-pigmented tumor  Metastic neuroblastoma with involvement of ophthalmic sympathetic nerve Medications  Prostaglandin analog eye drops (Xalatan, Lumigan, Travatan, and others  Latisse

Idiopathic Incontinentia pigmenti Ipsilateral facial and uveal arteriovenous and capillary angiomata, microphthalmia, heterochromia, and hypotony – simulates Sturge-­ Weber syndrome Trans Am Ophthalmol Soc 94:227–239, 1996

HOARSENESS, CUTANEOUS MANIFESTATIONS

Iris coloboma Arch Ophthalmol 118:1590–1591, 2000

AUTOIMMUNE DISEASES

Neurofibromatosis – Lisch nodules (iris hamartomas)

Dermatitis herpetiformis JAAD 22:325–326, 1990

Parry-Romberg syndrome Rortschr Ophthalmol 83:302–304, 1986

Lupus erythematosus – ulceration of laryngeal mucosa, edema of vocal cords, arytenoids or aryepiglottic folds, bowing or glottis gap between true vocal folds; vocal fold paralysis J Clin Rheumatol 13:278–279, 2007

Piebaldism Prenatal toxic or other noxious influences Proteus syndrome AD 140:947–953, 2004 Sturge-Weber syndrome

Pemphigus foliaceus – ulcerations with gray membranes J Eur Arch Otorhinolaryngol 264: 509–512, 2007

Xanthogranuloma – juvenile JXG Am J Ophthalmol 53:455–462, 1962

Pemphigus vulgaris – ulcerations with gray membranes ENT J 96:120–127, 2017; J Eur Arch Otorhinolaryngol 264: 509–512, 2007

Waardenburg's syndrome J Med Genet 34:656–665, 1997; Eye 12:353–357, 1998; Am J Med Genet 55:95–100, 1995

Relapsing polychondritis – destruction of laryngeal tissues Int J Dermatol 48:356–362, 2009

ACQUIRED

INFECTIONS AND INFESTATIONS

Hyperchromic heterochromia   Foreign body Surv Ophthalmol 28:409–411, 1984   Hyphema (hemorrhage in anterior chamber of eye)   Iris abscess  Leukemia  Lymphoma  Melanoma of iris, including metastatic iris melanoma Br J Ophthalmol 63:744–749, 1979   Melanosis bulbi (vs. pigment in anterior layers of iris)   Metallic siderosis (intraocular foreign body iron fragments)  Neurofibromatosis  Nevus of iris, including iris nevus (Cogan-Reese) syndrome Can J Ophthalmol 13:287–290, 1978   Nevus of Ota   Romberg’s syndrome (facial hemiatrophy)   Scleroderma, periorbital Am J Ophthalmol 90:858–861, 1980   Trauma - perforating injuries or contusions to eye  Xanthogranuloma Klin Monatsbl Augenheilkd 205:47–49, 1994

Bartonella bacilliformis(Carrion’s disease) Int J Dermatol 56:1442– 1444, 2017

Tuberous sclerosis (hypopigmented iris spot)

Histoplasmosis South Afr J HIV Med 28:693, 2017 Leishmaniasis – mucocutaneous leishmanisis (L. brasiliensis, L. panamensis, L. guyanensis, L. amazonensis); subglottic or laryngeal masses Iran J Parasitol 10:296–300, 2015; J Pathol Microbiol 52:62–64, 2009 Leprosy South Med J 87:937–940, 1994 Nasopharyngeal lingulatulosis (Marrara or Halzoun syndromePentastomiasis) Dermatologica 181:327–329, 1990 Papilloma virus papillomas – laryngeal papillomas Syphilis – papules of epiglottis and arytenoepiglottic folds J Coll Physician Surg Pak 28:S37–38, 2018 Tuberculosis Kekkau 68:637–643, 1993 Verruca vulgaris J Craniofac Surg 27:e397–398, 2016 Viral pharyngitis/laryngitis

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INFILTRATIVE DISORDERS

SYNDROMES

Amyloidosis(AA) Int J Dermatol 46:503–504, 2017;

Dubowitz syndrome – autosomal recessive, microcephaly, sloping forehead, telecanthus, erythema and scaling of face and extremities in infancy, sparse blond scalp and arched eyebrow hair, dysplastic low set ear pinnae, high pitched hoarse voice, delayed eruption of teeth, growth retardation, craniofacial abnormalities; syndactyly, cryptorchidism, hypospadius, developmental delay, transitory short stature, hyperactive behavior, blepharophimosis, ptosis of the eyelids, epicanthal folds, broad nose, palate anomalies, micrognathia, and severe atopic dermatitis Ped Derm 22:480–481, 2005; Am J Med Genet 63:277–289, 1996; Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959–964, 1993; Eur J Pediatr 144:574– 578, 1986; Am J Med Genet 4:345–347, 1979; J Med Genet 2:12–17, 1965

Dermatol Online J Nov 15, 2009 Xanthoma disseminatum Iran J Otorhinolaryngol 29:365–368, 2017

INFLAMMATORY DISORDERS Sarcoidosis – supraglottic granulomas, edematous pale and diffuse enlargement of supraglottic structures Rev Laryngol Oto Rhinol 130:133–136, 2009; Med J Austr 178:75–76, 2003; J Voice 16:283–288, 2002 Stevens-Johnson syndrome

METABOLIC DISORDERS Calcinosis cutis, tumoral Oral Surg Oral Med Oral Pathol 77:158– 166, 1994 Hypothyroidism NEJM 371:2321–2327, 2014; Am J Med Sci 314:333–337, 1997

Ehlers-Danlos syndrome type VIII Clin Exp Dermatol 41:771–774, 2016 Farber’s disease – autosomal recessive; rare lysosomal storage disease; lysosomal acid ceramidase deficiency; triad of granulomatous lesions of the larynx; subcutaneous nodules; painful joint deformities Ped Derm 26:44–46, 2009 Goltz’s syndrome – papillomatosis of the hypopharynx and larynx Eur J Dermatol 9:618–620, 1999

NEOPLASTIC DISEASES

Kindler’s syndrome – laryngeal stenosis Ped Derm 35:864–865, 2018

Leukemia - acute T-cell leukemia Nihon Jibinkoka Gakkai Kaiho 92:46–50, 1989

Laryngo-onycho-cutaneous syndrome(Shabbir syndrome) – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3(LAMA3A) Gene Reviews Seattle(WA) University of Washington, Seattle, 1993–2019; BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedica 2:15–25, 1986

Lymphoma – cutaneous T-cell lymphoma Brit Med J Case Reports Oct 9, 2017; non-Hodgkins B-cell lymphoma J Islam Republic Iran 28:21, 2014 Medullary carcinoma of the thyroid – MEN IIA, IIB – facial flushing, diarrhea, hoarseness, bone pain Clin Med Res 16:16– 28, 2018

PARANEOPLASTIC DISORDERS Bazex syndrome(acrokeratosis paraneoplastica) Necrobiotic xanthogranuloma with paraproteinemia Am J Dermatopathol 12:579–584, 1990 Pityriasis rubra pilaris with laryngeal carcinoma Clin Exp Dermatol 34:e919, 2009

PRIMARY CUTANEOUS DISEASES Benign symmetric lipomatosis (Madelung’s disease) – external compression of vocal cords, lipomas of tongue (limited mobility of tongue) J Dtsch Dermatol Ges 7:441–444, 2009 Epidermolysis bullosa simplex, generalized severe – hoarse cry in newborn Ped Derm 37:393–395, 2020 Epidermolysis bullosa, junctional – tracheolaryngeal edema; hoarse cry Ann Otol Rhinol Laryngol 10:861–865, 1992 Epidermolysis bullosa simplex, recessive – plectin mutation; hoarse cry at birth BJD 137:898–906, 1997; Ann Otol Rhinol Laryngol 101:861–865, 1992; dystrophic JAAD 77:809–830, 2017; DowlingMeara variant BJD 14:315–320, 2015

Lipoid proteinosis – autosomal recessive; mutation in ECM1- encoding extracellular matrix protein 1; deposition of hyaline on vocal cords; skin, oral mucosa; presents as hoarseness, beaded eyelid papules, generalized thickened skin, short tongue with thickened frenulum, comma shaped calcifications of amygdala; seizures, neuropsychiatric abnormalities Handbook Clin Neurol 132:317–322, 2015; J Eur Acad Dermatol Venereol 23:482–483, 2009; Dermatol Online 14:6, 2008 Pachyonychia congenita-white-to-pink thickening of laryngeal folds or exophytic mass; natal teeth, bushy eyebrows, follicular keratoses, angular cheilitis, unruly hair, thick nails, palmoplantar keratoderma with hyperhidrosis, hoarseness, cysts oral leukokeratosis; mutations in KRT6A, KRT6B, KRT6C, KRT16, KRT17 BJD 171:343–355, 2014; J Invest Dermatol Symp Proc 10:3–17, 2005 Sweet’s syndrome ENT J 94:282–284, 2015 Weaver syndrome – overgrowth syndrome with hypertonic muscles, exaggerated reflexes, micrognathia, thin hair, loose skin, low hoarse cry, soft doughy skin Am J Genetics 161A:2972–2980, 2013 Werner’s syndrome – hoarse voice, premature aging, cataracts, sclerodermoid skin atrophy, hyogonadism J Voice 22:509–511, 2008

Kimura’s disease – supraglottic/paraglottic mass externally distorting vocal cords Otolaryngol Head Neck Surg 135:989–-990, 2006

TOXINS

Lichen planus – mucosal vaginal syndrome J Coll Physician Surg Pak 20:478–479, 2010

Sulfur mustard – massive inflammation of the trachea with necrosis Toxicology 263:3–8, 2009

Human Papilloma Virus-Associated Immunodeficiency Syndromes

VASCULAR LESIONS Giant cell arteritis – involvement of branches of external carotid artery supplying the larynx Granulomatosis with polyangiitis Ped Derm 30:e37–42, 2013 Stroke

HUMAN PAPILLOMA VIRUSASSOCIATED IMMUNODEFICIENCY SYNDROMES WARTS: EXTENSIVE, RECURRENT, RECALCITRANT BJD 178:335–349, 2018; JAAD 73:367–381, 2015; Jnl Allergy Clin Immunol 130:1030–1048, 2012 Ataxia telangiectasia – autosomal recessive; oculocutaneous telangiectasias, radiosensitivity, combined immunodeficiency and progressive neurodegeneration; wart severe and refractory to treatment Common variable immunodeficiency – most prevalent immunodeficiency, broad range of clinical manifestations; warts uncommon but severe; disseminated warts reported DOCK8 deficiency – autosomal recessive form of hyper IgE syndrome; variable B, T, and NK cell cytopenia; eosinophilia; recurrent infections with staphylococcus and viruses (HSV, VZV, HPV); chronic warts JAMADerm 148:79–84, 2012 Epidermodysplasia verruciformis – EVER 1 and EVER 2 deficiency; flat wart-like hypopigmented or hyperpigmented papules; may coalesce as scaly patches or plaques or verrucous or seborrheic keratosis-like lesions frequently on sun exposed areas with greater malignant potential; at least 19 HPV phenotypes; HPV-5,3, and 10 most frequent GATA2 deficiency – autosomal dominant; human papilloma virusin 75% of cases, oral herpes simplex infections, varicella-zoster, non-tuberculous mycobacterial, Clostridium dificile infections, myeloid dysplasia, acute myelogenous leukemia; panniculitis, congenital lymphedema, clubbing, embolic stroke, bony infarcts, deep venous thrombosis; melanoma and non-melanoma skin cancers; sensorineural deafness, autoimmune thyroid disease (due to decreased Tregs); normal immunoglobulins

4 GATA2 SYNDROMES 1. Monocytopenia and mycobacterial infections(MONOMAC); myeloid leukemia, pulmonary alveolar proteinosis, erythema nodosum, lymphedema

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Idiopathic CD4 T-cell lymphopenia; not induced by HIV infection; presents with opportunistic infection, autoimmune disease or malignancy J Cut Med Surg 20:470–473, 2016 LAD-1(CD18 deficiency) – leukocyte adhesion deficiency type-1; impaired wound healing, gingivitis, periodontitis, and inflammatory bowel disease, all without pus; extensive warts of skin and mucosa MST 1 deficiency – mammalian sterile 20-like 1 deficiency  Neutropenia   B and T cell lymphopenia NEMO(IKBKG deficiency) – early susceptibility to bacterial and mycobacterial infection; ectodermal dysplasia; severe disseminated HPV, typically flat warts Netherton’s syndrome – autosomal recessive; HSV and HPV skin infections; SPINK5 mutation Severe combined immunodeficiency – absent T cells; widespread seborrheic dermatitis-like rash, morbilliform eruptions and extensive eczema; widespread cutaneous and plantar wart STK 4 deficiency – recurrent cutaneous viral infections with HSV, VZV, MCV, and HPV; chronic dermatitis resembling atopic dermatitis; persistent EBV viremia, lymphoproliferative syndrome WHIM syndrome – autosomal dominant; human papilloma virus infections of variable severity; recurrent bacterial infections, sinopulmonary infections; myelokathexis; gain of function mutation of CXCR4(receptor for chemokine ligand 12) JAAD 73:367–381, 2015  Cytopenias   Neutropenia    B and T cell lymphopenia   Decreased IgG and IgA   Normal IgM WILD syndrome – disseminated warts, immunodeficiency, primary lymphedema, and anogenital dysplasia with hypertrophic plaques; probably a form of GATA2 deficiency AD 144:366–372, 2008 Wiskott-Aldrich syndrome(WASP mutation) – X-linked; thrombocytopenia, atopic dermatitis, frequent pyogenic infections; case reports of recurrent or recalcitrant warts X-linked hyper IgM immunodeficiency syndrome (mutation in CD154) – affected males with recurrent bacterial and opportunistic infections early in life; recurrent oral ulcers and proctitis; susceptibility to viral infection is not a hallmark; common warts on hands, elbows, knees

SYNDROMES WITH EXTENSIVE WARTS AD 144:366–372, 2008 Clouston’s syndrome – alopecia, hyperpigmentation, sparse facial and body hair, dystrophic nails, keratoderma, mental retardation

2. Dendritic cell, monocyte, B lymphocyte(DCML), and NK lymphocyte deficiency; lymphedema

Klinefelter’s syndrome – infertile, small testes, sparse facial and body hair, delayed motor function, gynecomastia

3. Familial myelodysplastic syndrome

Mulvihill-Smith syndrome – low birth weight, growth delays, premature aged facial appearance, multiple pigmented nevi, hearing impairment, mental retardation

4. Emberger syndrome – primary lymphedema; myelodysplastic syndrome; congenital sensorineural hearing loss, lower limb and genital primary lymphedema   GATA2 cytopenias   Monocyte   B cell   NK cell   CD4+   Neutropenia ICF syndrome – autosomal recessive(rare); immunodeficiency, centromere instability, facial anomalies syndrome

Netherton’s syndrome WHIM syndrome – warts, hypogammaglobulinema, infections, myelokathexis AD 144:366–372, 2008 WILD syndrome – disseminated warts, diminished cell-mediated immunity, primary lymphedema, anogenital dysplasia; perianal hypertrophic plaque AD 144:366–372, 2008 Wiskott-Aldrich syndrome X-linked hyper-IgM immunodeficiency syndrome – oral ulcers, pneumonia

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HYPERHIDROSIS JAAD 81:657–666, 2019; JAAD 64:690–695, 2011; Int J Derm 38:561–567, 1999; JAAD 20:713–726, 1989

GENERALIZED HYPERHIDROSIS 1. Spinal cord injuries – profuse sweating of face, neck, upper trunk with lesions at or above T6   Autonomic dysregulation   Congenital autonomic dysfunction with universal pain loss   Orthostatic hypotension  Paraplegia Arch Neurol 34:536–539, 1977   Post-traumatic syringomyelia 2. Peripheral neuropathy   Charcot-Marie-Tooth disease   Diabetic autonomic neuropathy JAAD 64:690–695, 2011  Fabry’s disease – more common in females BJD 157:331–337, 2007   Familial dysautonomia (Riley-Day syndrome)   Cold exposure   Congenital autonomic dysfunction with universal pain loss   Peripheral nerve injury JAAD 64:690–695, 2011  Phakomatosis pigmentokeratotica – coexistence of large nevus sebaceous and speckled lentiginous nevus; multilobulated pink nodules representing connective tissue nevus; seizures, hyperhidrosis, peripheral neuropathy; high incidence of vitamin D-resistant rickets JAAD 63:1–22, 2010; Ped Derm 25:76–80, 2008; Arch Surg 43:341–375, 1941  Post-sympathectomy   Reflex sympathetic dystrophy JAAD 64:690–695, 2011  Speckled lentiginous nevus syndrome – speckled lentiginous nevus with ipsilateral sensory and motor small fiber neuropathy, hyperhidrosis, spinal muscle atrophy with fasciculations, dysesthesias, muscle weakness, muscle atrophy, nerve palsy JAAD 72:328–332, 2015; Ped Derm 26:298–301, 2009; Eur J Dermatol 12:133–135, 2002; ipsilateral shortening of limb and vertebral malformations Acta DV(Stockh)74:327–334, 1994 3. Probable brain lesions  Acquired neuromyotonia(Isaacs syndrome) JAAD 64:690–695, 2011   Arnold-Chiari malformation JAAD 64:690–695, 2011  Asymmetric hyperhidrosis – central nervous system lesions of cortex, basal ganglia or spinal cord   Brain abscess JAAD 64:690–695, 2011  Encephalitis JAAD 64:690–695, 2011  Hypothalamic stroke – hemihyperhidrosis Neurology 22:1394– 1396, 2001   Hypothermia (Hines-Bannick syndrome)   Without hyperthermia   Hypertension, post-traumatic  Meningioma JAAD 64:690–695, 2011  Olfactory   Parkinson’s disease JAAD 64:690–695, 2011  Paroxysmal sympathetic hyperactivity after acquired brain injury Neurotrauma 3:1515–1520, 2014; Neurology Research 29:680– 682, 2007   Post-influenza diencephalitis Wiad Lek 33:149–152, 1980   Syringomyelia – hyperhidrosis over face and upper arms  Shapiro syndrome – episodic hypothermia and hyperhidrosis; abnormalities of midline central nervous system structures Neurology 97:254–256, 2001; Brain 92:423–436, 1969  Tumors

4. Association with intrathoracic neoplasms or lesions  Paroxysmal unilateral hyperhidrosis (cervical rib, osteoma, pulmonary adenocarcinoma, bronchogenic carcinoma, mesothelioma) AD 117:659–661, 1981  Segmental anhidrosis associated with unilateral adenocarcinoma of the lung; with compensatory hyperhidrosis on contralateral chest wall JAAD 65:438–440, 2011  Unilateral hyperhidrosis and hypothermia – manifestation of contralateral intrathoracic tumor BJD 174:1147–1148, 2016 5. Association with systemic illness  Acrodynia (mercury intoxication) – profuse sweating; red edematous hands and feet, hypertension, severe periumbilical pain, irritability Ped Derm 29:199–201, 2012; Pediatr Nephrol 22:903–906, 2009; Arch Dis Child 62:293–295, 1987; Lancet 29:829–830, 1948; Arch Dermatol Syphilol 26:215–237, 1932; Rev Med Fr 3:51–74, 1830  Acromegaly Br Med J 2(6195):901–902, 1979  AIDS – episodic spontaneous hyperhidrosis with hypothermia Clin Inf Dis 29:210, 1999   Alcoholism, chronic  Anorexia nervosa – drenching night sweats during weight recovery   Apert syndrome (acrocephalosyndactyly) Cutis 52:205–208, 1993  Book syndrome – autosomal dominant; canities, hyperhidrosis, premolar hypodontia Am J Hum Genet 2:240–263, 1950  Brucellosis JAAD 64:690–695, 2011  Carcinoid syndrome – foregut (stomach, lung, pancreas) – bright red geographic flush, sustained, with burning, lacrimation, wheezing, sweating Int J Derm 38:561–567, 1999;   Cardiogenic shock   Chediak-Higashi syndrome   Chronic pulmonary disease JAAD 64:690–695, 2011   Cold exposure Lancet ii:1073–1074, 1978   Congestive heart failure JAAD 64:690–695, 2011  Dermatomyositis   Diabetes mellitus Int J Derm 38:561–567, 1999   Ectodermal dysplasia syndromes JAAD 64:690–695, 2011   Emotional stress AD 123:890–892, 1987  Epidermolysis bullosa - late onset junctional epidermolysis bullosa (epidermolysis junctionalis progressiva) – bullae of hands and feet, nail dystrophy, loss of dermatolyphic pattern, tooth enamel abnormalities, hyperhidrosis; loss of dermatoglyphs, waxy hyperkeratosis of dorsal hand, atrophic skin of lower leg, transverse ridging and enamel pits of teeth, nail atrophy, amelogenesis imperfect, blisters on elbows, knees, and oral cavity BJD 164:1280–1284, 2011; BJD 144:1054–1057, 2001   Febrile illnesses   Fructose intolerance - deficit of aldolase B   Fucosidosis type III   Gaucher's disease, type I  Gout Curr Ther 16:863–867, 1998   Graves’ disease JAAD 48:641–659, 2003   Herbicide poisoning   Hodgkin’s disease JAAD 64:690–695, 2011   Hot environment Int J Derm 38:561–567, 1999  Hyperpituitarism JAAD 64:690–695, 2011   Hypertension, post-traumatic  Hyperthyroidism JAAD 64:690–695, 2011; JAAD 26:885–902, 1992  Hypoglycemia Int J Derm 38:561–567, 1999  Idiopathic Cutis 77(Suppl 5):9–16, 2006   Infections, acute and chronic   Insecticide poisoning   Klippel-Trenaunay syndrome JAAD 64:690–695, 2011

Hyperhidrosis  Lupus erythematosus, polymyositis overlap syndrome J Rheumatol 25:1638–1641, 1998  Lymphoma JAAD 64:690–695, 2011   Maffucci’s syndrome JAAD 64:690–695, 2011  Malaria JAAD 64:690–695, 2011  Menopause Curr Ther 16:863–867, 1998  Obesity  Over-clothed Int J Derm 38:561–567, 1999   Parkinson's disease JAAD 64:690–695, 2011  Phakomatosis pigmentokeratotica - coexistence of an organoid nevus and a checkerboard papular speckled lentiginous nevus; organoid nevus associated with hypophosphatemic vitamin D-resistant rickets JAAD 55:S16–20, 2006; Eur J Dermatol 10:190–194, 2000; Ped Derm 15:321–323, 1998; AD 134:333– 337, 1998  Phenylketonuria JAAD 64:690–695, 2011  Pheochromocytoma JAAD 64:690–695, 2011; Int J Derm 38:561–567, 1999  POEMS syndrome (Takatsuki syndrome, Crowe-Fukase syndrome) - osteosclerotic bone lesions, peripheral polyneuropathy, hypothyroidism, and hypogonadism; sclerodermoid changes (thickening of skin), either generalized or localized (legs), cutaneous angiomas, blue dermal papules associated with Castleman’s disease (benign reactive angioendotheliomatosis), diffuse hyperpigmentation, maculopapular brown-­violaceous lesions, purple nodules JAAD 55:149–152, 2006; JAAD 44:324– 329, 2001, JAAD 21:1061–1068, 1989; JAAD 12:961–964, 1985, AD 124:695–698, 1988, Cutis 61:329–334, 1998; JAAD 40:808– 812, 1999  Porphyria JAAD 64:690–695, 2011   Pregnancy – hyperhidrosis, spares palms   Primary hyperhidrosis JAAD 64:690–695, 2011  Psychiatric disease – generalized anxiety disorder JAAD 64:690–695, 2011   Respiratory failure Int J Derm 38:561–567, 1999  Rickets  Ross' syndrome – segmental anhidrosis with segmental compenstory hyperhidrosis, hyporeflexia, tonic pupil JAAD 55:S111–112, 2006; AD 142:264, 2006; JAAD 28:308–312, 1993  Russell-Silver syndrome – intrauterine and post-natal growth retardation; triangular facies, childhood hyperhidrosis, limb asymmetry, café au lait macules, blue sclerae, achromia, 5th finger clinodactyly, genital dysmorphia  Schopf syndrome (oligodontia, hypotrichosis, palmoplantar hyperkeratosis, apocrine hidrocystomas of eyelid margins) JAAD 10:922–925, 1984  Scurvy   Septic shock JAAD 64:690–695, 2011  Speckled lentiginous nevus syndrome – speckled lentiginous nevus with ipsilateral sensory and motor neuropathy, hyperhidrosis, spinal muscle atrophy with fasciculations, dysesthesias, muscle weakness Eur J Dermatol 12:133–135, 2002; ipsilateral shortening of limb and vertebral malformations Acta DV (Stockh)74:327–334, 1994  Spontaneous periodic hypothermia (Shapiro’s syndrome) JAAD 64:690–695, 2011   Syncopal states   Thermal stimuli  Thymoma JAAD 64:690–695, 2011  Thyrotoxicosis Int J Derm 38:561–567, 1999  Tuberculosis JAAD 64:690–695, 2011  Tyrosinemia type II (Richner-Hanhart syndrome) JAAD 35:857– 859, 1996  Uremia

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 Visceral disease – asymmetric sweating Fed Proc Am Soc Exp Biol 8:87–88, 1949  Vomiting 6. Night sweats  Acromegaly Clin Endocrinol 53:601–608, 2000   Carcinoid syndrome   Chediak-Higashi syndrome  Dermatomyositis   Diabetes mellitus   Drug withdrawal   Dumping syndrome  Dysautonomic states, including familial dysautonomia (Riley-Day syndrome)   Febrile illness  Gout Cutis 69:336–338, 2002  Heat  Hodgkin's disease – nocturnal hyperhidrosis Cutis 69:336–338, 2002  Hyperpituitarism  Hyperthyroidism  Hypoglycemia  Idiopathic hyperhidrosis Int J Derm 38:561–567, 1999; Pediatrics 64:698, 1979  Insulinoma  Menopause  Obesity   Obstructive sleep apnea   Phenylketonuria  Pheochromocytoma JAAD 46:161–183, 2002   Polycythemia vera Orv Metrl 157:1743–1751, 2016  Porphyria  Pregnancy   Prinzmetal’s angina Ann Int Med 107:121, 1987  Rickets   Scurvy in infants   Subacute bacterial endocarditis  Tuberculosis   Turner syndrome Clin Genet 52:63–64, 1997  Vasculitis 7. Compensatory   After sympathectomy  Associated with diffuse anhidrosis- occurs adjacent to or distant from areas of anhidrosis or hypohidrosis  Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis JAAD 69:909–915, 2013; Ped Derm 29:756– 758, 2012; AD 121:361–367, 1985  Harlequin syndrome – damage to sympathetic innervation of one side of face; decreased sweating and flushing on one side of face; compensatory increased sweating and flushing on normal side of face BJD 169:954–956, 2013  Spinal cord – anhidrosis related to myelopathy causes compensatory hyperhidrosis above the lesion  Stroke – hemihyperhidrosis on the side contralateral to the stroke with face and arm more affected 8. Neurological associations   Emotional factors (anxiety) Int J Derm 38:561–567, 1999   Central nervous system lesions   Gustatory hyperhidrosis Int J Derm 38:561–567, 1999  Nevus spilus syndrome – ipsilateral hyperhidrosis, muscular weakness, dysesthesia Eur J Dermatol 12:133–135, 2002

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  Multiple sclerosis – unilateral sweating   Myasthenia gravis Tohoku J Exp Med 164:285–291, 1991   Olfactory hyperhidrosis Int J Derm 38:561–567, 1999   Parkinson's disease   Paroxysmal unilateral hyperhidrosis Sympathetic discharge    Shock and syncope   Intense pain   Alcohol   Drug withdrawal Curr Ther 16:863–867, 1998 9. Pharmacologic  Adrenergic agents (dopamine, epinephrine, isoproterenol, ephedrine) JAAD 64:690–695, 2011   Alcohol intoxication or withdrawal JAAD 64:690–695, 2011   Amanita muscaria mushrooms – ingestion; cholinergic mushroom toxicosis; swollen lips and tongue; altered mental status, vomiting, diarrhea, incontinence, sweating, excess salivation MMWR 68:483–484, 2019  Anticholinesterases/cholinergics (acetylcholine, pilocarpine, methacholine, physostigmine) JAAD 64:690–695, 2011  Antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors) JAAD 64:690–695, 2011   Antidiabetic agents (glyburide, insulin) JAAD 64:690–695, 2011  Antiemetics Cutis 77(Suppl 5):9–16, 2006  Antipsychotics JAAD 64:690–695, 2011  Antipyretic agents (naproxen, aspirin, piroxicam) JAAD 64:690– 695, 2011  Anxiolytics JAAD 64:690–695, 2011  Betel nut (areca nut) chewing – betel quid (areca nut, leaf of betel pepper, slaked lime paste from shells, coral, or limestone) autonomic and psychoneurologic effects; cholinergic activation, flushing, tachycardia, warmth, euphoria, alertness, hypotension, angioedema, hyperhidrosis, myocardial infarction Clin Toxicol 39:355–360, 2001   Cholinergic drugs   Chronic arsenic intoxication  Clomipramine – serotonin syndrome; diaphoresis, mental status changes, dyscoordination, hyperreflexia, shivering, tremor, agitation, myoclonus, fever JAAD 56:848–853, 2007  Cyclobenzaprine poisoning – paradoxical diaphoresis Ann Int Med 101:881, 1984   Fluoxetine hydrochloride Cutis 77(Suppl 5):9–16, 2006   Emetic drugs  Hyperandrogenism AD 136:430–431, 2000   Insulin overdose  Meperidine   Methamphetamine abuse JAAD 69:135–142, 2013  Monoamine oxidase inhibitors - serotonin syndrome; diaphoresis, mental status changes, dyscoordination, hyperreflexia, shivering, tremor, agitation, myoclonus, fever JAAD 56:848–853, 2007   Nicotinic acid  Omeprazole Postgrad Med J 75:701–702, 1999  Opiates JAAD 64:690–695, 2011  Oxaliplatin JAAD 64:690–695, 2011  Paroxetine – sudden withdrawal of paroxetine JAAD 56:848–853, 2007  Physostigmine Cutis 69:336–338, 2002  Pilocarpine Cutis 69:336–338, 2002  Propranalol Cutis 69:336–338, 2002  Serotonin syndrome – selective serotonin reuptake inhibitors –; diaphoresis, mental status changes, dyscoordination, hyperreflexia, shivering, tremor, agitation, myoclonus, fever; lorcaserin (serotonin agonist) JAAD 81:1059–1069, 2019; JAAD 56:848– 853, 2007; 352:1112–1120, 2005   Tricyclic antidepressants Cutis 69:336–338, 2002

 Tryptophan – serotonin syndrome; diaphoresis, mental status changes, dyscoordination, hyperreflexia, shivering, tremor, agitation, myoclonus, fever JAAD 56:848–853, 2007  Venlafaxine Cutis 69:336–338, 2002 10. Toxins  Acrodynia AD 124:107–109, 1988  Insecticides 11. Trauma – Endoscopic thoracic sympathectomy (T2-­T4) – facial and axillary anhidrosis with compensatory hyperhidrosis of lower chest and abdomen Cutis 71:68–70, 2003 12. Heat, humidity, and exercise Curr Ther 16:863–867, 1998

LOCALIZED HYPERHIDROSIS Ped Derm 10:341–343, 1993 1. Idiopathic unilateral circumscribed hyperhidrosis AD 137:1241– 1246, 2001; Ped Derm 17:25–28, 2000 2. Gustatory sweating associated with: Clin Pediatr 32:629–631, 1993  Auriculotemporal syndrome(von Frey's syndrome) – damage to auriculotemporal nerve due to injury, abscess, after parotitis, surgery in parotid area; linear flush and/or sweating on cheek, over parotid region, neck, and temporal scalp after eating Ped Derm 26:302–305, 2009; Ann Plast Surg 57:581–584, 2006; Ped Derm 17:415–416, 2000; AD 133:1143–1145, 1997; Rev Neurol 2:97–104, 1923; after facial trauma J Oral Maxillofac Surg 55:1485–1490, 1997; parotidectomy Laryngoscope 107:1496– 1501, 1997; after thyroidectomy BJD 79:519–526, 1967   Central nervous system lesions  Chocolate Curr Ther 16:863–867, 1998   Citric acid Curr Ther 16:863–867, 1998  Coffee Curr Ther 16:863–867, 1998  Diabetic neuropathy SMJ 95:360–362, 2002; Oral Surg Oral Med Oral Pathol 77:113–115, 1994; Am J Gastroenterol 86:1514– 1517, 1991  Encephalitis  Glycopyrronium bromide(glycopyrrolate) – mydriasis for hyperhidrosis JAMA 322:264–265, 2019  Greater auricular nerve sweating after radical neck surgery Plast Reconstr Surg 49:639–642, 1972  Gustatory sweating – hyperhidrosis of face knee JAMA 142:901– 902, 1950  Gustatory sweating syndrome of the submandibular gland Ear Nose Throat J 79:111–112, 2000; following removal of the submandibular gland Br Dent J 158:17–18, 1985   Herpes zoster parotitis Ann Neurol 21:559,1987  Horner’s syndrome – medullary infarction, syringomyelia, multiple sclerosis, intraspinal tumors, aortic aneurysm, cervical lymphadenopathy, surgery, regional anesthesia, tumors - transient unilateral hyperhidrosis and vasoconstriction of the face  Hypertensive diencephalic syndrome – hyperhidrosis and blotchy erythema of face and neck with salivation, tachycardia, and sustained hypertension   Olfactory hyperhidrosis Clin Exp Dermatol 12:298–299, 1987  Pancoast tumor – hemifacial gustatory sweating Am J Med 82:1269–1271, 1987   Parotid abscess  Parotidectomy Acta Otolaryngol 48:234–252, 1957   Peanut butter Curr Ther 16:863–867, 1998  Postherpetic gustatory sweating and flushing Ann Neurol 21:559–563, 1987   Spicy food Curr Ther 16:863–867, 1998

Hyperhidrosis 477   Submental gustatory sweating  Sympathetic nerve damage of head and neck  Syringomyelia   Thoracic sympathectomy  Trauma J Oral Surg 35:306–308, 1977  Vagus nerve-induced gustatory sweating of upper arm after cervical sympathectomy Br Med J I:688–689, 1958 Glomus tumors Klippel-Trenaunay syndrome Maffucci’s syndrome Ann DV 126:817–821, 1999 Paroxysmal idiopathic localized hyperhidrosis  Localized hyperhidrosis associated with central nervous system disease, peripheral neuropathy, stroke, trauma, syringomyelia, tabes dorsalis, cervical rib, vertebral osteoma, mesothelioma, lung cancer 3. Associations with:  Acrodynia - mercury poisoning – butterfly rash, flushing, perspiration of face, palmar erythema JAAD 45:966–967, 2001  Acro-osteolysis associated with spinal dysraphism – hyperhidrosis of the affected limb Ped Derm 18:97–101, 2001   Adjacent to area of anhidrosis  Angioblastoma(Nakagawa) BJD 143:223–224, 2000   Around leg ulcer(axon reflex stimulation)  Autosomal recessive exfoliative ichthyosis – congenital erythroderma, diffuse hyperkeratosis, palmoplantar keratoderma, palmoplantar peeling, hyperhidrosis, erosions; mutation in cysteine protease inhibitor A(cystatin A) BJD 172:1628–1632, 2015  Blue rubber bleb nevus(vascular malformation) AD 137:1241– 1246, 2001; AD 116:924–929, 1996  Book syndrome - autosomal dominant; palms and soles hyperhidrotic - aplasia of premolar teeth, premature graying(canities) Am J Hum Genet 2:240–263, 1950  Bronchial carcinoma – with pleural spread – unilateral thoracic hyperhidrosis Br Med J 2(6035):563, 1976   Buerger’s disease AD 137:1241–1246, 2001   Burning feet syndrome(Gopalan's syndrome) Carcinoid syndrome  Causalgia   Charcot-Marie Tooth syndrome  Chilblains  Compensatory hyperhidrosis, after thoracic sympathectomy Lancet 351:1136, 1998  Eccrine nevus – skin colored papules, brown papules, depressed brown patches, perianal skin tag, solitary pore, draining mucoid material; localized unilateral hyperhidrosis Ped Derm 31:611–612, 2014JAAD 51:301–304, 2004; Clin Exp Derm 22:246–247, 1997; Cutis 53:259–261, 1994; JAAD 27:115, 1992; nevus sudoriferus – area of increased sweat production AD 96:67–68, 1967  Eccrine angiomatous nevus(hamartoma) – brown and pink plaque AD 145:241–243, 2009; vascular nodule; macule, red plaque, acral nodule of infants or neonates; painful, red, purple, blue, yellow, brown, skin-­colored nodule or plaque AD 142:1351– 1356, 2006; Ped Derm 23:365–368, 2006; Ped Derm 23:516–517, 2006; Ped Derm 22:175–176, 2005; JAAD 51:301–304, 2004; Cutis 71:449–455, 2003; JAAD 47:429–435, 2002; Ped Derm 18:117–119, 2001; JAAD 37:523–549, 1997; Ped Derm 14:401– 402, 1997; Ped Derm 13:139–142, 1996; AD 129:105–110, 1993; NY State J Med 68:2803–2806, 1968; Virchow Arch Pathol Anat 16:160, 1859; skin colored nodule Ped Derm 27:93–94, 2010; skin-colored nodule with blue papules JAAD 41:109–111, 1999; blue plaque or nodule Dermatologica 155:206–209, 1977   Eccrine pilar angiomatous hamartoma AD 137:1241–1246, 2001   Emotional - palmoplantar and axillary

 Encephalitis Epidermolysis bullosa – recessive JAAD 64:690– 695, 2011  Erythrocyanosis  Fibrous hamartoma of infancy – eccrine sweating over lesion; hairy plaque on arm Ped Derm 32:533–535, 2015; JAAD 64:579–586, 2011; J Pediatr Surg 46:753–755, 2011; J Cutan Pathol 34:39–43, 2007; JAAD 41:857–859, 1999; Ped Pathol 14:39–52, 1994; Int J Ped Otorhinolaryngol 26:173–176, 1993; Med Cutan Ibero Lat Am 18:175–177, 1990  Focal palmoplantar and oral mucosa(gingival) hyperkeratosis syndrome(MIM:148730)(hereditary painful callosities) – palmoplantar keratoderma with hyperhidrosis, leukoplakia(gingival keratosis), and cutaneous horn of the lip JAAD 52:403–409, 2005; BJD 146:680–683, 2002; Oral Surg 50:250, 1980; Birth Defects 12:239–242, 1976; Arch Int Med 113:866–871, 1964  Frostbite  Glomus tumors AD 137:1241–1246, 2001; JAAD 41:109–111, 1997; hyperhidrosis may precede appearance of glomus on a limb Ped Derm 19:402–408, 2002   Gopalan's syndrome AD 137:1241–1246, 2001  Granulosis rubra nasi – erythema of tip of nose, upper lip, chin; telangiectasias, small cysts Ann DV 123:106–108, 1996; Cutis 10:463, 1972  Heat Curr Ther 16:863–867, 1998   Herpes zoster   Hyperhidrotic malformations JAAD 29:274–275, 1993   Hyperthyroidism – palms and soles JAAD 26:885–902, 1992  Ichthyosis bullosa of Siemens – mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray rippled hyperkeratosis of extremities, lower trunk, flexures; hypertrichosis; circumscribed patchy scaling(mauserung); palmoplantar blistering with hyperhidrosis BJD 140:689–695, 1999; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986  Idiopathic unilateral hyperhidrosis Arch Dermatol Syphilol 51:370–372, 1945  Intrathoracic tumors – mesothelioma, lung cancer(segmental hyperhidrosis) JAAD 64:690–695, 2011   Iron deficiency Ann Clin Biochem 32:509–510, 1995   Jadassohn-Lewandowsky syndrome  Jakac-Wolf syndrome – palmoplantar keratoderma with squamous cell carcinoma, gingival dental anomalies, hyperhidrosis JAAD 53:S234–239, 2005  Klippel-Trenaunay Weber syndrome JAAD 56:541–564, 2007; JAAD 56:242–249, 2007; Cutis 60:127–132, 1997; Arch Gen Med(Paris) 3:641–672, 1900  Localized hyperhidrosis on the backs of the hands JAAD 12:937–942, 1985  Localized paroxysmal hyperhidrosis Am J Med Sci 221:86–88, 1951  Maffucci's syndrome - angiomatous lesion with hyperplastic sweat glands  Malignant mesothelioma – paroxysmal unilateral hyperhidrosis Arch Neurol 40:256, 1983  Mastocytosis, systemic Am J Med Sci 342:409–415, 2011  Mucinous eccrine nevus – swollen sweaty fifth toe Ped Derm 36:538–539, 2019; red plaque in fold of wrist Ped Derm 25:573– 574, 2008  Nail-patella syndrome Genetic Skin Disorders, Second Edition, 2010, pp.242–246  Olfactory hyperhidrosis – facial hyperhidrosis Clin Exp Dermatol 12:298–299, 1987  Following opiate abuse – persistent focal hyperhidrosis Addiction 94:923–924, 1999  Pachydermoperiostosis AD 137:1241–1246, 2001

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 Perilesional  Palmoplantar keratoderma - Papillon Lefevre syndrome – mutation in cathepsin C gene Cutis 93:193–198, 2014  Parotid abscess  Parotitis  Phakomatosis pigmentokeratotica AD 134:333–337, 1998; localized hyperhidrosis in speckled lentiginous nevus Ped Derm 25:76–80, 2008  POEMS syndrome AD 137:1241–1246, 2001  Porokeratotic eccrine ostial and dermal duct nevus – resemble nevus comedonicus; linear keratotic papules with central plugged pit; may be verrucous; filiform; anhidrotic or hyperhidrotic; most common on palms and soles JAAD 43:364–367, 2000; JAAD 24:300–1, 1991; Cutis 46:495–497, 1990  Post-sympathectomy compensatory hyperidrosis JAAD 64:690– 695, 2011  Pretibial myxedema JAAD 23:250–254, 1990  Primary focal hyperhidrosis – palmoplantar, axillary, craniofacial, inguinal JAAD 64:690–695, 2011; Eur Neurol 44:112–116, 2000  Pulmonary adenocarcinoma – unilateral segmental hyperhidrosis Chest 114:1215–1217, 1998  Raynaud’s phenomenon/disease JAAD 64:690–695, 2011  Reflex sympathetic dystrophy Cutis 68:179–182, 2001; AD 137:1241–1246, 2001; Am J Dis Child 142:1325–1330, 1988  Rheumatoid arthritis  Ross' syndrome – unilateral tonic pupils, generalized areflexia, progressive segmental anhidrosis with compensatory band of hyperhidrosis Curr Ther 16:863–867, 1998  Striate palmoplantar keratoderma – autosomal dominant; hyperkeratosis of knees, intermittent blisters, and hyperhidrosis; mutation in desmoglein-1 BJD 166:36–45, 2012  Sudoriparous angioma BJD 119:111–1113, 1988  Tufted angioma AD 146:758–763, 2010; AD 136:905–914, 2000; Ped Derm 14:53–55, 1997; JAAD 33:124–126, 1995; JAAD 28:516–517,520, 1993; Clin Exp Dermatol 17:344–345, 1992  Unilateral hyperhidrosis of the trunk Acta Med Scand 168:17–20, 1960  Varicella – segmental hyperhidrosis preceding varicella J S C Med Assoc 80:504–505, 1984  Venous malformation JAAD 37:523–549, 1997 4. Neurological associations  Auriculotemporal syndrome  Brain tumors  Cerebral infarction – unilateral hyperhidrosis Neurology 38:1679– 1682, 1988  Causalgia  Diabetic neuropathy  Fear  Gustatory  Hemiplegia vegetativa alterna(ipsilateral Horner’s syndrome with contralateral hemihyperhidrosis) – due to posterior cerebral artery occlusion Stroke 26:702–704, 1995  Horner’s syndrome  Olfactory hyperhidrosis  Post-encephalitis  Posttraumatic forehead hyperhidrosis Headache 30:64–68, 1990  Sympathetic neurologic lesions  Syringomyelia  Tabes dorsalis  Tethered spinal cord syndrome – unilateral hyperhidrosis Ped Derm 15:486–487, 1998  Thoracic sympathectomy

5. Pharmacologic causes  Adrenergic agents  Cholinergic agents  Tricyclic antidepressants J Clin Psychiatry 51:258–259, 1990 6. Physiologic causes  Anxiety  Local heat  Pressure 7. Vasomotor causes  Arteriovenous fistulae  Cold injury  Erythrocyanosis  Frostbite  Glomangiomas  Mafucci syndrome  Myocardial ischemia  Raynaud's phenomenon  Sudoriporous hemangioma  Symmetrical lividity of palms and soles  Vibration

HYPERHIDROSIS OF PALMS AND SOLES Acrokeratoelastoidosis Anorexia nervosa Am J Clin Dermatol 6:165–173, 2005 Aquagenic keratoderma Indian J Dermatol 60:212, 2015 Arteriovenous fistula Book’s syndrome – autosomal dominant; premature graying, premolar hypodontia, palmoplantar hyperhidrosis Am J Hum Genet 2:240–245, 1950 Bothnian type palmoplantar keratoderm BMC Dermatol 2016 June 3 16(1)7;doi:10.1186/S12895-016-0044-3 Chloracne Dermatol Clin 12:569–576, 1994 Cold injury Dermatopathia pigmentosa reticularis – autosomal dominant; reticulate pigmentation of trunk, neck, and proximal extremities, alopecia, nail changes(mild onychodystrophy), palmoplantar hyperkeratosis, loss of dermatoglyphics, hyperpigmented tongue, hypo- or hyperhidrosis, non-scarring blisters of dorsal hands and feet, dark areolae, thin eyebrows, Ped Derm 24:566–570, 2007; J Dermatol 24:266–269, 1997; JAAD 26:298–301, 1992; AD 126:935–939, 1990; Dermatol Wochenschr 138:1337, 1958 Dyskeratosis congenita(Zinsser-Cole-Engmann syndrome) – X-linked recessive – cutaneous atrophy and pigmentation; mental retardation, short stature, deafness, conjunctivitis with obstruction of lacrimal ducts, blepharitis, palmoplantar keratoderma, palmoplantar hyperhidrosis, urethral anomalies, esophageal stenosis, choanal atresia, hepatic abnormalities, frontal lobe atrophy, intracranial calcifications, hypogonadism, osteoporosis, avascular necrosis JAAD 77:1194–1196, 2017; Ped Derm 26:176–179, 2009; J Med Genet 12:339–354, 1975 Emotional stress Epidermolysis bullosa simplex(Weber-Cockayne) Erythromelalgia Graves’ disease JAAD 48:641–659, 2003

Hyperkeratotic Lesions Greither's palmoplantar keratoderma(transgrediens et progrediens palmoplantar keratoderma) – hyperkeratoses extending over Achilles tendon, backs of hands, elbows, knees; livid erythema at margins Cutis 65:141–145, 2000; Dermatology 187:309–311, 1993 Herpes zoster Hidrotic ectodermal dysplasia Dermatologica 158:168–174, 1979 Hyperhidrosis palmaris et plantaris Ichthyosis bullosa of Siemens – mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray rippled hyperkeratosis of extremities, lower trunk, flexures; hypertrichosis; circumscribed patchy scaling(mauserung); palmoplantar blistering with hyperhidrosis BJD 140:689–695, 1999; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986 Increased sympathetic response through T2-3 ganglia Keratolysis exfoliativa Keratosis palmaris et plantaris Mal de Meleda – autosomal dominant, autosomal recessive transgrediens with acral erythema in glove-like distribution; perioral erythema and hyperkeratosis; hyperhidrosis; pseudo-ainhum; lingua plicata, syndactyly, hairy palms and soles, high arched palate, lefthandedness Dermatology 203:7–13, 2001; AD 136:1247–1252, 2000; J Dermatol 27:664–668, 2000; Dermatologica 171:30–37, 1985 Metastases - cutaneous metastases from a chondroblastoma initially presenting as unilateral palmar hyperhidrosis JAAD 40:325–327, 1999 Naegeli-Franceschetti-Jadassohn syndrome – autosomal dominant; absent dermatoglyphics; reticulated hyperpigmentation, palmoplantar keratoderma, dental abnormalities, abnormal sweating keratin 14 mutation BJD 177:945–959, 2017

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Pretibial myxedema JAAD 46:723–726, 2002 Primary hyperhidrosis (essential of primary focal) JAAD 64:690– 695, 2011 Raynaud's phenomenon or disease Reflex sympathetic dystrophy Br Med J 310:1645–1648, 1995 Rheumatoid arthritis Richner-Hanhart syndrome(tyrosinemia type II) - autosomal recessive; tyrosine aminotransferase deficiency; chromosome 16q22-q24; painful palmoplantar keratoderma with circumscribed keratoses, bullae may occur; dendritic corneal ulcers, mental retardation; palmoplantar hyperhidrosis; signs include tearing, redness, pain and photophobia progressing to superficial and deep dendritic ulcers; mental retardation; aggregated tonofibril bundles on electron microscopy; crystal structures J Pediatr 126:266–269, 1995; AD 130:507–511, 1994; AD 126:1342–1346, 1990 Schopf-Schulz-Passarge syndrome(hypotrichosis, palmoplantar hyperkeratosis, apocrine hidrocystomas of eyelid margins, nail dystrophy) – oligodontia; red palms and soles with focal dryness; maceration with hyperhidrosis; finger and toenail dystrophy; mutation in WNT10A BJD 171:1211–1214, 2014; Ped Derm 30:491–492, 2013; JAAD 65:1066–1069, 2011; AD 140:231–236, 2004; Acta DV 88:607–612, 2008; JAAD 10:922–925, 1984 Symmetrical lividity of the soles Cutis 64:175–176, 1999; Int J Dermatol 17:739–744, 1978; BJD 37:123–125, 1925 Unna-Thost palmoplantar keratoderma – diffuse non-epidermolytic palmoplantar keratoderma – autosomal dominant; mutations in keratin 16 Ped Derm 20:195–198, 2003; Hum Mol Genet 4:1875– 1881, 1995; mutation in keratin 1 JID 103:764–769, 1994 WNT10A deficiency – severe tooth agenesis BMC Med Genetics 24:88, 2016; Am J Hum Genet 81:821–828, 2007

Nail patella syndrome Nagashina type palmoplantar keratoderma Ann DV 146:125–130, 2019 Odonto-onycho-dermal dyplasia – oligodontia with small widely spaced conical peg-shaped teeth, hypodontia, absence of secondary teeth; palmoplantar keratoderma, hyperhidrosis, dystrophic nails, erythematous telangiectatic, reticulated atrophic malar and ala nasal patches with vermiculate scarring JAAD 57:732–733, 2007; Am J Med Genet 14:335–346, 1983 Olmsted syndrome Pachyonychia congenita, Jadassohn Lewandowsky; type II – natal teeth, bushy eyebrows, follicular keratoses, angular cheilitis, unruly hair, thick nails, palmoplantar keratoderma with hyperhidrosis, hoarseness, cysts oral leukokeratosis; mutations in KRT6A, KRT6B, KRT6C, KRT16, KRT17 BJD 171:343–355, 2014; JAMADerm 150:146–153, 2014; Ped Derm 7:33–38, 1990; JAAD 19:705–711, 1988 Pachydermoperiostosis Mymensingh Med J 26:939–943, 2017; Z Hautkr 56:175–186, 1981 Palmoplantar keratodermas JAAD 64:690–695, 2011 Papillon-Lefevre syndrome – autosomal recessive; diffuse transgradiens palmoplantar keratoderma with hyperhidrosis; periodontal disease with shedding of primary and permanent dentition; recurrent cutaneous and systemic pyodermas; psoriasiform plaques of elbows and knees Cutis 84:269–271, 2009; JAAD 49:S240–243, 2003; J Periodontol 66:413–420, 1995; Ped Derm 11:354–357, 1994 Phakomatosis pigmentokeratotica of Happle Acta DV 82:55–57, 2002 Pitted keratolysis BJD 137:282–285, 1997

UNILATERAL HYPERHIDROSIS Usually associated with secondary hyperhidrosis JAAD 64:690– 695, 2011

HYPERKERATOTIC LESIONS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Anti-synthetase syndrome – mechanics’ hands, Raynaud’s phenomenon, interstitial lung disease, anti-Jo-1 antibody AD 141:779–784, 2005 Autoimmune progesterone dermatitis CD4+ lymphopenia – Indonesian man with giant claws(warts) JAAD 66:292–311, 2012 Common variable immunodeficiency – progressive hypogammaglobulinemia, cell mediated immunity defects; warts; mutations in inducible costimulator gene mutations; transmembrane activator and calcium modulator and cyclophilin ligand interactor mutations(TNF RSF 13B); B cell-activator factor receptor mutations(TNFRSF13C); CD19 mutations; mutation of S homolog 5 JAAD 66:292–311, 2012 Dermatomyositis – hyperkeratotic cuticles AD 110:866–867, 1995; tender hyperkeratotic palmar papules in palmar creases of fingers with central white coloration; dermatomyositis with MDA-5(CADM-40) (melanoma differentiation-associated gene 5)MDA 5 – RNA-specific helicase; all with interstitial lung disease JAAD 65:25–34, 2011

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DOCK8 deficiency syndrome(dedicator of cytokinesis 8 gene)(aka autosomal recessive hyper-IgE syndrome)DOCK8 – involved in T cell polarization and activation; atypical guanine exchange factor; interacts with Rho GTPases(CDC42 AND RAC) which mediate actin cytoskeletal reorganization; hematologic stem cell homing and mobilization – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; red papules of neck – molluscum contagiosum; warts, widespread dermatitis(atopic dermatitislike(24% at birth; Job’s 81% dermatitis at birth), asthma, cutaneous staphylococcal abscesses; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation AD 148:79– 84, 2012 Graft vs. host disease, chronic – follicular keratosis and plugs JAAD 72:690–695, 2015; AD 138:924–934, 2002; acral keratotic form simulating warts Australas J Dermatol 40:161–163, 1999; hyperkeratotic plaques AD 147:1345–1346, 2011 Hyper IgE syndrome – warts, atopic dermatitis, recurrent pneumonia with pneumatoceles, recurrent skin staphylococcal abscesses; mutation in signal transducer and activator of transcription 3 and tyrosine kinase 2 JAAD 66:292–311, 2012 HyperIgM immunodeficiency syndrome(XHIM) – X-linked recessive; low IgA,G,E; mutation in gene for CD40 ligand; upper and lower respiratory tract infections; painful ulcers of tongue and buccal mucosa JAAD 66:292–311, 2012 Lupus erythematosus – systemic – hyperkeratotic and ragged cuticles discoid lupus erythematosus BJD 98:507–520, 1978; cutaneous horn AD 121:837–838, 1985 Mixed connective tissue disease – hyperkeratotic cuticles Morphea - linear morphea Clin Exp Dermatol 24:467–468, 1999; JAAD 38:366–368, 1998; BJD 134:594–595, 1996; generalized morphea – keratoses Pemphigoid nodularis – hyperkeratotic plaques and nodules JAAD 45:747–754, 2001; JAAD 27:863–867, 1992; AD 118:937–939, 1982 Pemphigus erythematosus - personal observation Pemphigus foliaceus – pemphigus foliaceus resembling seborrheic keratosis AD 126:543–544, 1990; post-pemphigus acanthomata Int J Derm 36:194–196, 1997; endemic pemphigus of El Bagre region of Colombia JAAD 49:599–608, 2003 Pemphigus vegetans JAMA 314:2296–2297, 2015 Scleroderma – hyperkeratotic plaques over phalanges containing amyloid Trans St John’s Hosp Dermatol Soc 57:177–180, 1971; hyperkeratotic cuticles Severe combined immunodeficiency syndrome – desquamative erythematous, morbilliform or vesiculopapular eruption of newborn(3 weeks); erythroderma, seborrheic dermatitis-like eruption; morbilliform eruptions, lichen planus-like eruptions, dermatitis; mutations in cytokine common gamma chain, JAK3, RAG1 or RAG2, IL-7Rgamma, adenosine deaminase JAAD 66:292–311, 2012; Ped Derm 26:213–214, 2009; AD 144:342–346, 2008; Dermatol Therapy 18:176–183, 2005; Ped Derm 17:91–96, 2000; AD 136:875–880, 2000; J Pediatr 123:564–572, 1993; Ped Derm 8:314–321, 1991

CONGENITAL LESIONS Congenital mucinous eccrine nevi – red-brown hyperkeratotic plaques over ankle, foot, and toes AD 148:140–142, 2012 Ectopic nail with polydactyly JAAD 53:1092–1093, 2005

DEGENERATIVE DISEASES Disuse hyperkeratosis – of toes in paraplegic BJD 163:646–648, 2010; of scalp SKINmed 10:46–47, 2012 Neurotrophic ulcers including those associated with neuropathies – begins as fissured callosity on metatarsal heads and heels

DRUG-INDUCED Anti-PD-1 therapy(nivolumab/pembrolizumab – lichenoid eruptions, vitiligo, dermatitis, red papules with scale, red papules and nodules, inflammation surrounding seborrheic keratosis, dyshidrosiform palmar lesions, penile erosions JAMADerm 152:1128–1136, 2016; JAAD 74:455–461, 2016 Bleomycin - hyperkeratotic plaques on elbows and knees JAAD 40:367–398, 1999; AD 107:553–555, 1973 Cyclosporine – hair-like hyperkeratoses Hautarzt 46:841–846, 1995 Dabrafenib – keratoacanthomas; plantar calluses, seborrheic keratosis, acneiform eruptions, epidermoid cysts, alopecia, verruca vulgaris BJD 167:1153–1160, 2012 Docetaxel – fixed erythrodysesthetic plaque proximal to infusion site JAAD 58:545–570, 2008 Erbitux – personal observation Hepatitis B vaccine – necrolytic acral erythema; psoriasiform dermatitis, acral erythema and scale, cheilitis, verrucous papules of eyelids and around nose BJD 171:1255–1256, 2014 Leflunamide therapy – eruptive keratoacanthomas JAMADerm 152:105–106, 2016; Derm Online J 19:18968, 2013 Lenalidomide-induced perforating folliculitis – hyperkeratotic umbilicated nodules BJD 173:618–620, 2015 Lithium-induced pseudo CTCL – follicular spiny hyperkeratosis JAAD 44:308–309, 2001; lithium-induced follicular hyperkeratosis Clin Exp Dermatol 21:296–298, 1996 Sorafenib(multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of feet, hyperkeratotic plaque or blister of feet, red patches on pressure points, red swollen fingertips, gray blisters of fingerwebs, angular cheilitis, perianal dermatitis JAAD 58:545–570, 2008;BJD 158:592–596, 2008; inflamed seborrheic keratoses JAAD 61:360–361, 2009 Sunitinib(multikinase inhibitor) – acral erythema with hyperkeratotic plaques JAAD 58:545–570, 2008 Telaprevir – perforating disorder – black hyperkeratotic nodules JAMADerm 150:1371–1372, 2014 Vemurafenib – multiple nodules of cheeks; follicular plugging; exuberant seborrheic dermatitis-like hyperkertosis of face; hand and foot reaction; diffuse spiny follicular hyperkeratosis; cobblestoning of forehead JAAD 71:217–227, 2014; JAAD 67:1375–1379, 2012 Voriconazole – in immunosuppressed patients; chronic phototoxicity with aggressive squamous cell carcinomas; sunburn-like erythema, multiple lentigines, multiple actinic keratoses, cheilitis, exfoliative dermatitis, pseudo-porphyria cutanea tarda, telangiectasias JAAD 62:31–37, 2010

Hyperkeratotic Lesions

EXOGENOUS AGENTS Foreign body granuloma Podoconiosis – multilobulated hyperkeratotic nodules of feet; bare feet exposed to red clay from alkaline volcanic rock JAAD 65:214– 215, 2011

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inoculation BJD 144:444–445, 2001; hematogenous disseminated tuberculosis – annular verrucous plaques of buttocks, scrotal ulcers, hyperkeratotic plaques of sole Clin Inf Dis 49:1402–1404,1450– 1451, 2009 North American blastomycosis – hyperkeratotic nodule of nose NEJM 373:955–961, 2015 Onychomycosis – thickened nails

INFECTIONS AND INFESTATIONS Alternariosis – red scaly patches Clin Inf Dis 32:1178–1187, 2001; hyperkeratotic hyperpigmented plaque of leg ulcer; following laceration Ped Derm 27:99–101, 2010 Bacillary angiomatosis Botryomycosis in AIDS JAAD 16:238–242, 1987 Candida – hypertrophic and dystrophic nails JAAD 65:1219–1227, 2011; chronic mucocutaneous candidiasis with candida granuloma Ann Rev Med 32:491–497, 1981 Coccidioidomycosis – hyperkeratotic nodules and plaques AD 140:609–614, 2004 Cryptococcosis Demodicidosis – spinulosis of the face BJD 138:901–903, 1998; seborrheic keratosis-like lesions BJD 170:1219–1225, 2014 Dermatophytes – hyperkeratosis with cutaneous horns Ann DV 125:705–707, 1998 Ecthyma – staphylococcal or streptococcal Erythrasma – disciform erythrasma; intertriginous and perigenital; Corynebacterium minutissimum; red to brown irregularly shaped and sharply marginated scaly and slightly creased patches of groin, axillae, intergluteal, submammary flexures, toe webs coral-red fluorescence with Wood's light examination due to coproporphyrin; toe clefts are most frequent location; acanthosis nigricans and normal follicular openings of face and trunk may show coral pink fluorescence Rev Infect Dis 4:1220–1235, 1982 Favus – Trichophyton schoenleinii BJD 148:1057, 2003 Fusarium solani – hyperkeratotic facial plaque AD 101:598–600, 1970 Hepatitis C infection – necrolytic acral erythema; psoriasiform, hyperpigmented hyperkeratotic plaques of hands, feet, knees JAAD 63:259–265, 2010 Herpes zoster in AIDS JAAD 20:637–642, 1989; AD 126:1048– 1050, 1990 HIV infection - follicular hyperkeratotic spicules JAAD 36:476–477, 1997; IRIS(immune reconstitution syndrome) – warts JAAD 66:292–311, 2012 Impetigo – crusted red plaque J Drugs in Dermatol 12:369–374, 2013 Leishmaniasis - cutaneous horn AD 123:168–169, 1987 Leprosy – hyperkeratotic and verrucous lesions of the lower extremities Indian J Lepr 64:183–187, 1992 Molluscum contagiosum JAAD 43:409–432, 2000 Mucormycosis – violaceous hyperkeratotic plaque with central eschar JAMA Derm 150:79–80, 2014 Mycobacterium avium-intracellulare – scaling plaques AD 126:1108–1110, 1990 Mycobacterium terrae – hyperkeratotic plaque and osteomyelitis of fingertip following metal staple puncture BJD 152:727–734, 2005 Mycobacterium tuberculosis - lupus vulgaris – crusted hyperkeratotic plaque with nodules and scarring; tuberculosis verrucosa cutis Cutis 78:309–316, 2006; Int J Derm 39:856–858, 2000; due to BCG

Phaeohyphomycosis(subcutaneous phaeohyphomycosis) – Exophiala jeanselmii Cutis 72:132–134, 2003; Alternaria JAAD 59:905–907, 2008 Pinta - tertiary(late phase) – hyperkeratoses of forearms, elbows, knees, ankles, legs, palms and soles Pitted keratolysis Protothecosis – pyoderma-like lesion BJD 146:688–693, 2002 Pyoderma - personal observation Scabies, crusted(Norwegian scabies) Cutis 99:202–204, 2017; JAMA 313:298–299, 2015; Cutis 92:193–198, 2013; An Bras Dermatol 87:910–913, 2012; BJD 158:1247–1255, 2008; AD 143:626–628, 2007; Dermatology 197:306–308, 1998; AD 124:121– 126, 1988; hyperkeratotic papules of knuckles; hyperkeratotic nodule of instep Ped Derm 27:93–94, 2010; scabies-associated acquired perforating dermatosis JAAD 51:665–667, 2004; hyperkeratosis of penis BJD 161:195–197, 2009; of scalp Ped Derm 27:525–526, 2010; red-brown scaling hyperkeratotic plaque of groin Clin Exp Dermatol 45:587–588, 2020 Schistosoma haematobium – vulvar lesions resemble condyloma acuminata Clin Exp Dermatol 8:189–194, 1983 Scopulariopsis brevicaulis – opaque thick nails JAAD 66:494–502, 2012 Sporotrichosis – scaly patches Syphilis, secondary – rupioid lesions Indian J Dermatol Venereol 75:201–202, 2009 Tinea corporis, cruris, pedis; tinea pedis – resembling crusted scabies; scutular favus-like tinea pedis - Microsporum gypseum; tinea capitis – favus(Trichophyton schoenleinii) favus(S) - yellowish cup-shaped crusts(scutula) JAAD 53:931–951, 2006; Dermatologica 125:369–381, 1962; Trichodysplasia spinulosa(trichodysplasia of immunosuppression; viral-associated trichodysplasia spinulosa; pilomatrix dysplasia; cyclosporine induced folliculodystrophy) – follicular papules, keratotic spines of face and ears; eyebrow and scalp alopecia; facial disfigurement; trichodysplasia-associated polyoma virus JAAD 75:1–16, 2016; AD 142:1643–1648, 2006; JAAD 52:540–541, 2005 Varicella-zoster chronic hyperkeratotic lesions in AIDS - personal observation Warts - giant disseminated verrucosis(HPV2)(giant verrucous claw hands and feet) associated with idiopathic CD4 lymphopenia; large annular warts of trunk AD 146:69–73, 2010 ; Cutis 63:91–94, 1999  Generalized verrucosis(multiple warts) BJD 170:1182–1186, 2014; JAAD 66:292–311, 2012   Epidermodysplasia verruciformis    WHIM syndrome   WILD syndrome(warts, immunodeficiency, lymphedema, and anogenital dysplasia)    SCID(severe combined immunodeficiency syndrome)    CVID(common variable immunodeficiency)    XHIM(hyperIgM immunodeficiency syndrome   GATA2 deficiency(includes MONOMAC syndrome, DCML, Emberger syndrome(lymphedema and myelodysplasia)(familial acute leukemia and myelodysplasia) – monocytopenia, B-cell

482 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 and natural kellier cell lymphopenia, myeloid leukemias, disseminated mycobacterial infection, human papilloma virus infection, fungal infection; GATA2-transcription factor in early hematopoietic differentiation and lymphatic and vascular development; primary alveolar proteinosis; panniculitis; erythema nodosum-like lesions; primary lymphedema BJD 170:1182–1186, 2014   HyperIgE syndrome    Wiskott-Aldrich syndrome   HIV disease    Organ transplant recipients    Idiopathic CD4+ T lymphocytopenia    Chronic lymphocytic leukemia   Atopic dermatitis   Netherton’s syndrome    DOCK 8(dedicator of cytokinesis 8 protein) Yaws – crab yaws JAAD 54:559–578, 2006

Pellagra – hyperpigmented scaly photodermatitis; hyperkeratotic and hyperpigmented elbows, knees, ankles, skin over spinous processes BJD 164:1188–1200, 2011 Phrynoderma - hyperkeratotic spicules AD 120:919–921, 1984 Pregnancy – hyperkeratosis of the nipple JAMA Derm 149:722–726, 2013 Reactive perforating collagenosis JAAD 60:463–469, 2009 Renal failure, chronic - hyperkeratotic spicules JAAD 36:476–477, 1997; uremic follicular hyperkeratosis JAAD 26:782–783, 1992 Scurvy Tyrosinemia type II - painful calluses AD 130:507–512, 1994 Zinc deficiency

NEOPLASTIC DISEASES Acantholytic acanthoma – papule or nodule JAAD 19:783–786, 1988

INFILTRATIVE LESIONS

Acantholytic dyskeratotic epidermal nevus JAMADerm 151:1259– 1260, 2015

Amyloidosis - lichen amyloidosis BJD 161:1217–1224, 2009

Acquired digital fibrokeratoma JAAD 12:816–821, 1985

Colloid milium, papuloverrucous variant BJD 143:884–887, 2000

Actinic keratoses JAAD 37:392–394, 1997

Erdheim-Chester disease(non Langerhans cell histiocytosis) – hyperkeratotic pigmented patches of legs; xanthelasma-like periorbital yellow papules and plaques; CD68+, CD163+, CD1a-, Langerin(CD207)-; BRAF mutations JAAD 74:513–520, 2016

Basal cell carcinoma - pseudohorn Cutis 48:379, 1991

Langerhans cell histiocytosis – nail involvement; hyperkeratotic dystrophic nails Ped Derm 25:633–634, 2008 Lichen myxedematosus – hyperkeratotic plaque Verruciform xanthoma - disseminated verruciform xanthoma – hyperkeratotic yellow plaques; subungual pink papules Cutis 93:307–310, 2014; AD 36:665–670, 2000

INFLAMMATORY DISEASES Folliculitis spinulosa decalvans – scarring alopecia, persistent pustules, keratotic papules Cutis 98:175–178, 2016 Perforating folliculitis - personal observation

Bowen’s disease - HPV type 56-associated Bowen’s disease – longitudinal melanonychia; pigmented hyperkeratotic plaque BJD 167:1161–1164, 2012 Connective tissue nevus – mimicking linear epidermal nevus JAAD 16:264–266, 1987 Eccrine angiokeratomatous hamartoma – red-violaceous keratotic nodule of lateral malleolus JAAD 55:S104–106, 2006 Eccrine angiomatous hamartoma BJD 141:167–169, 1999 Eccrine syringofibroadenoma - nodule JAAD 13:433–436, 1985 Epidermal nevus – round and velvety epidermal nevus BJD 180:201–202, 2019 Fibro-osseous pseudotumor of the digit – hyperkeratotic brown papule of the the toe tip AD 147:975–980, 2011; Cancer 58:2103– 2109, 1986

Polymyositis - fingertip hyperkeratosis AD 129:1207–1208, 1993

Ganglion cyst overlying acromioclavicular joint – verrucous multilobulated tumor JAAD 64:1206–1208, 2011

Rosai-Dorfman disease, cutaneous(sinus histiocytosis with massive lymphadenopathy) – multiple hyperkeratotic papulonodules JAAD 65:890–892, 2011

Granular cell myoblastoma – hyperkeratotic papule; prurigo nodularis-­like lesions Int J Derm 20:126–129, 1981

Sarcoid – keratotic spines and palmar pits BJD 95:93–97, 1976

Hyperkeratotic lichen planus-like reactions combined with infundibulocystic hyperplasia AD 140:1262–1267, 2004

Toxic epidermal necrolysis – healing with verrucous hyperplasia BJD 149:1082–1083, 2003

HPV high grade dysplasia – hyperpigmented hyperkeratotic plaque of scrotum JAMADerm 153:1332–1334, 2017

METABOLIC DISEASES

Inflammatory linear verrucous epidermal nevus – linear dermatitic and/or psoriasiform plaques; often on leg; pink keratotic plaque Ped Derm 36:404–405, 2019; JAAD 49:976, 2003

Acromegaly – onychauxis(hypertrophy of nail)

AD 113:767–769, 1977; AD 104:385–389, 1971

Aminoaciduria – rupioid photosensitive lesions Dermatologica 156:244–250, 1978

Kaposi’s sarcoma BJD 142:501–505, 2000; hyperkeratotic Kaposi’s sarcoma in AIDS with massive lymphedema BJD 142:501–505, 2000

Chronic obstructive pulmonary disease(COPD) - elbows JAAD 13:681–682, 1985; Cutis 52:91–92, 1993 Crohn's disease - hyperkeratotic spicules JAAD 36:476–477, 1997 Diabetes mellitus – neuropathic hemorrhagic calluses of feet Disseminated verruciform xanthoma BJD 151:717–719, 2004 Dysglobulinemia - hyperkeratotic spicules JAAD 36:476–477, 1997 Fabry’s disease – angiokeratomas AD 140:1440–1446, 2004

Keratoacanthoma – eruptive keratoacanthomas The Dermatologist June 2019, p.20–22; multiple keratoacanthomas of Ferguson-Smith JAAD 74:437–451, 2016 Large cell acanthomas - hyperkeratotic plaques JAAD 8:840–845, 1983 Lymphoma – verrucous CTCL Clin Exp Dermatol 21:205–208, 1996; pilotropic CTCL - keratotic spicules AD 132:683–687, 1996;

Hyperkeratotic Lesions Woringer-­Kolopp disease - hyperkeratotic plaque AD 120:1045– 1051, 1984; annular hyperkeratotic plaques of hands and feet BJD 163:651–653, 2010; follicular CTCL – follicular keratosis JAAD 48:448–452, 2003; CTCL mimicking seborrheic keratosis BJD 147:1264–1265, 2002; granulomatous CTCL – hyperkeratotic plaques JAAD 69:366–374, 2013; CTCL in dark skin JAAD 60:359–375, 2009; nail dystrophy in CTCL AD 146:1287–1291, 2010; anaplastic large cell lymphoma Ped Derm 29:498–503, 2012;

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Pseudoepitheliomatous, micaceous, and keratotic balanitis JAAD 54:369–391, 2006 Seborrheic keratosis, including stucco keratosis

amelanotic acral lentiginous melanoma – resembles wart BJD 155:561–569, 2006; verrucous and keratotic melanoma Histopathology 23:453–458, 1993; Am J Dermatopathol 4:403–410, 1982; seborrheic keratosis-like melanoma AD 143:373–376, 2007

Squamous cell carcinoma Otolaryngol Clin North Am 26:265–277, 1993; squamous cell carcinoma of legs of black women – brown hyperkeratotic plaques of black women JAAD 65:221–222, 2011; JAAD 47:524–529, 2002; squamous cell carcinoma in situ JAAD 47:524–529, 2002; diffuse epidermal and periadnexal squamous cell carcinoma in situ – diffuse erythema and hyperkeratosis of face, neck, and scalp JAAD 53:623–627, 2005; verruciform squamous cell carcinoma JAAD 54:369–391, 2006; squamous cell carcinoma of the nail apparatus BJD 156:871–874, 2007; HPV 26-associated squamous cell carcinoma of nail beds BJD 157:788–794, 2007; red or white hyperkeratotic plaque of penis JAAD 62:284–290, 2010; squamous cell carcinoma of vulva in ILVEN; hypertrophic vulvar plaque Cutis 89:273–275, 2012; of the penis NEJM 374:164, 2016

Merkel cell carcinoma – verrucous nodule of cheek Cutis 97:290– 295, 2016

Subungual exostosis - hyperkeratotic nodule of fingertip Cutis 98:128–129, 2016; Ped Derm 13:212–218, 1996

Multiple myeloma – hyperkeratotic filiform follicular spicules JAAD 49:736–740, 2003; JAAD 36:476–477, 1997

Syringoacanthoma - seborrheic keratosis-like lesion AD 120:751– 756, 1984

Nevoid hyperkeratosis of the nipple JAAD 46:414–418, 2002; BJD 142:382–384, 2000; JAAD 41:325–326, 1999

Trichilemmal cyst nevus – multiple subcutaneous nodules with cystic lesions with and without comedones, filiform hyperkeratoses JAAD 57:S72–77, 2007

Melanocytic nevi – inflammatory nevi evolving into halo nevi in children BJD 152:357–360, 2005; keratotic melanocytic nevus Int J Derm 29:713–715, 1990 Melanoma – amelanotic melanoma AD 144:416–417, 2008;

Nevus comedonicus Nevus corniculatus – filiform keratoses, cutaneous horns, and giant comedones BJD 122:107–112, 1990 Nevus tricholemmocysticus – multiple pilar cysts; filiform hyperkeratoses, comedo-like plugs, osteomalacia, bone lesions JAAD 57(Suppl):S72–77, 2007 Onychomatricoma – thick yellow discoloration of nail plate; longitudinal ridging Ped Derm 24:46–48, 2007; banded or diffuse thickening of nail with yellowish discoloration, splinter hemorrhages, and transverse overcurvature(thick yellow nail) Cutis 96:121–124, 2015 Paget's disease of the nipple – cutaneous horn J Surg Oncol 29:237–239, 1985 Papillary eccrine adenoma – pomegranate-like appearance J Dermatol 24:773–776, 1997 Penile horn(cutaneous horn of the penis) Urology 30:156–158, 1987; J Urol 132:1192–1193, 1984 Porokeratosis - porokeratosis plantaris discreta JAAD 10:679–682, 1984; porokeratosis of Mibelli AD 122:586–587, 589–590, 1986; pink-white plaque Cutis 79:22,53–54, 2007; JAAD 52:553–555, 2005; Gior Ital d Mal Ven 28:313–355, 1893; of the penis AD 142:1221–1226, 2006; porokeratosis palmaris, plantaris et disseminata Dermatology 201:158–161, 2000; linear porokeratosis AD 142:1059–1064, 2006; Ped Derm 21:682–683, 2004; AD 135:1544–1555,1547–1548, 1999; Ped Derm 4:209, 1987; AD 109:526–528, 1974; eruptive pruritic papular porokeratosis J Dermtol 19:109–112, 1992; porokeratosis ptychotropica – Blaschkoesque, serpiginous, annular, hyperpigmented verrucous plaques of intertriginoua areas and buttocks Ped Derm 37:248–250, 2020; JAMA Derm 149:1099–1100, 2013; BJD 132:150–151, 1995 Porokeratotic adnexal ostial nevus(conifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic, filiform lesions with comedones; presents as red patch with red and atrophic linear and curvilinear erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAMADerm 154:1078–1079, 2018; JAMA Derm 149:869–870, 2013; JAAD 61:1060–1069, 2009; BJD 141:315–322, 1999; BJD 103:435–441, 1980; BJD 101:717–722, 1979

Trichilemmal horn Am J Dermatopathol 18:543–547, 1996; palmar cutaneous horn AD 120:386–387, 1984; BJD 100:303–309, 1979 Verrucous carcinoma – of mouth Cancer 89:2597–2606, 2000; Dermatology 192:217–221, 1996; J Craniomaxillofac Surg 17:309– 314, 1989; Surg 23:670–678, 1948; of umbilicus AD 141:779–784, 2005; of feet and legs JAAD 56:S2–32, 2007; of the scalp JAAD 56:506–507, 2007; of face – hyperkeratotic nodule of cheek BJD 165:694–696, 2011 Warty dyskeratoma – face, neck, scalp, axillae Woringer-Kolopp disease(pagetoid reticulosis) JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939

PARANEOPLASTIC DISORDERS Acanthosis nigricans JAAD 54:745–762, 2006 Bazex syndrome – papulosquamous lesions of nose and ears JAAD 54:745–762, 2006 Keratoacanthoma visceral carcinoma syndrome – cancers of the genitourinary tract AD 139:1363–1368, 2003; AD 120:123–124, 1984 Necrolytic acral erythema – hyperpigmented hyperkeratotic plaques of feet and shins JAAD 67:962–968, 2012 Sign of Leser-Trelat – eruptive inflammatory seborrheic keratoses associated with internal malignancy, immunosuppression, HIV disease JAAD 54:745–762, 2006; JAAD 35:88–95, 1996; JAAD 21:50–55, 1989 Skin spicules – paraneoplastic intertriginous filiform seborrheic keratoses associated with marginal zone B-cell lymphoma JAAD 60:852–855, 2009

PHOTODERMATOSES Actinic cheilitis – hyperkeratotic, scaling, erosive cheilitis JAAD 66:173–184, 2012 Photolichenoid drug eruptions

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

PRIMARY CUTANEOUS DISEASES

Erythrokeratoderma variabilis BJD 143:1283–1287, 2001

Acanthoma fissuratum - personal observation

Flegel's disease(hyperkeratosis lenticularis perstans) AD 133:910– 914, 1997; Cutis 48:201–204, 1991; JAAD 16:190–195, 1987

Acanthosis nigricans; of the nipple JAAD 52:529–530, 2005 Acquired relapsing self-healing Blaschko dermatitis JAAD 31:849– 852, 1994

Follicular ichthyosis BJD 111:101–109, 1984 Frontal fibrosing alopecia - personal observation

Callosities

Granular parakeratosis(axillary granular parakeratosis) – brown-gray hyperkeratotic papules and plaques in the intertriginous areas J Drugs Dermatol 16:810–812, 2017; Cutis 92:61,65–66, 2013; AD 147:997–998, 2011; JAAD 59:177–178, 2008; Cutis 80:55–56, 2007; JAAD 52:863–867, 2005; Ped Derm 20:215–220, 2003; Ped Derm 19:146–147, 2002; submammary granular parakeratosis – punctate hyperkeratosis JAAD 40:813–814, 1999; associated with obesity JAAD 81:1037–1057, 2019

Clavus

Perforating granuloma annulare - personal observation

Collodion baby Ann Dermatol Syphiligr 3:149–15, 1884

Grover’s disease – transient and/or persistent acantholytic dermatosis

Acrokeratoelastoidosis BJD 106:337–344, 1982 Acrokeratosis verruciformis Aquagenic syringeal acrokeratoderma JAAD 45:124–126, 2001 Atopic hand-foot dermatitis Ped Derm 18:102–106, 2001 Bullous ichthyosiform erythroderma

Confluent and reticulated papillomatosis J Dermatol 27:598–603, 2000; Int J Derm 31:480–483, 1992 Congenital trichoid keratosis - cutaneous horns on scalp AD 128:1549–15550, 1992 Darier's disease, including hemorrhagic acral Darier’s disease Hautarzt 51:857–861, 2000; onychauxis(hypertrophy of nail) Disseminated spiked hyperkeratosis AD 117:412–414, 1981 Dowling-Degos disease, acantholytic variant(Galli-Galli disease) JAAD 45:760–763, 2001; Hautarzt 33:378–383, 1982 Ectopic nail - cutaneous horn JAAD 10:114–116, 1984 Elastosis perforans serpiginosa – hyperkeratotic annular plaques; seen in Down’s syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum, Rothmund-Thomson syndrome, acrogeria, Ehlers-Danlos type IV, scleroderma, penicillamine Ped Derm 23:219–224, 2006; JAAD 51:1–21, 2004 Epidermolysis bullosa - alpha6-beta4 epidermolysis bullosa – onychogryphosis; yellow-brown discoloration of teeth with enamel defects BJD 169:115–124, 2013; ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013; hyperkeratotic lesions in recessive dystrophic epidermolysis bullosa – differentiation between benign hyperkeratosis vs. squamous cell carcinoma BJD 172:769–773, 2015 Epidermolysis bullosa; non-Herlitz junctional epidermolysis bullosa with collagen XVII mutation – palmoplantar callosities JAAD 52:371–373, 2005; AD 122:704–710, 1986; Dermatologica 152:72–86, 1976; hyperkeratotic lesions of legs BJD 170:1056–164, 2014 Epidermolysis bullosa, epidermolytic type – palmoplantar callosities JAAD 42:1051–1066, 2000 Epidermolysis bullosa simplex – palmoplantar callosities JAAD 42:1051–1066, 2000 Epidermolytic acanthoma BJD 141:728–730, 1999 Epidermolytic ichthyosis(formerly epidermolytic hyperkeratosis) BJD 164:442–447, 2011 Erosive pustular dermatosis of the scalp – in elderly; erosions, sterile pustules, scarring alopecia; sign of chronic actinic damage JAMADerm 152:694–697, 2016; AD 147:1368–1370, 2011; AD 147:252–253, 2011; AD 145:1340–1341, 2009; JAAD 60:521–522, 2009; AD 144:795–800, 2008; Ped Derm 23:533–536, 2006; AD 139:712–714, 2003; Dermatol Surg 27:766–767, 2001; JAAD 28:96–98, 1993; Hautarzt 43:576–579, 1992; BJD 118:441–444, 1988(S); BJD 100:559–566, 1979; chronic atrophic erosive dermatosis of the scalp and extremities JAAD 57:421–427, 2007

Harlequin fetus(harlequin ichthyosis)(ichthyosis congenital fetalis) – autosomal recessive; rigid plates; severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis; mutation in ABCA 12(adenosine triphosphate binding cassette A12); keratinocyte lipid transfer associated with lamellar granule formation and lipid transfer via lamellar granules on the surface of keratinocytes Harlequin fetus Ped Derm 31:539–546, 2014; Ped Derm 26:575–578, 2009; BJD 158:611–613, 2008; BJD 155:204–206, 2006; AD 142:914–918, 2006; BJD 153:811–814, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982 Hyperkeratosis of the nipple and areola(hyperkeratosis areolae mammae) AD 137:1327–1328, 2001; JAAD 41:274–276, 1999; Eur J Dermatol 8:131–132, 1998; JAAD 13:596–598, 1985; AD 126:687, 1990; estrogen-induced Cutis 26:95–96, 1980; associated with CTCL JAAD 32:124–125, 1995; Int J Derm 29:519–520, 1990; ichthyosis, ichthyosiform erythroderma, acanthosis nigricans, Darier’s disease JAAD 46:414–418, 2002; BJD 142:382–384, 2000; JAAD 41:382–384, 2000 Hyperkeratotic dermatitis of the palms BJD 107:195–201, 1982 Ichthyosis bullosa of Siemens(superficial epidermolytic ichthyosis) – autosomal dominant; mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray rippled hyperkeratosis of extremities, lower trunk, flexures; peeling; hypertrichosis; circumscribed patchy scaling(mauserung); palmoplantar blistering with hyperhidrosis Ped Derm 30:469–472, 2013; Ped Derm 27:653–654, 2010; Curr Prob Derm 14:71–116, 2002; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986; BJD 140:689– 695, 1999; Arch Derm Res 282:1–5, 1990; Arch Derm Syph 175:590–608, 1937 Neonatal ichthyosiform erythroderma, hyperpigmented verrucous and cerebriform plaques of heels and neck BJD 176:249–251, 2017 Ichthyosis hystrix, Curth-Macklin type – hyperkeratotic lesions of elbows, knees in parallel grooves(zebra stripe pattern); verrucous plaques; exophytic spiky hyperkeratosis; palmoplantar keratoderma; KRT1 mutation BJD 175:1372–1375, 2016; BJD 168:456–458 2013; AD 147:999–1001, 2011; AD 141:779–784, 2005; Am J Hum Genet 6:371–382, 1954 Ichthyosis hystrix, Lambert type – widespread hyperpigmented hyperkeratotic confluent plaques of trunk and extremities BJD 156:1027–1031, 2007; Am Hum Genet 6:371–382, 1954 Ichthyosis vulgaris palmaris et plantaris dominans – form of ichthyosis vulgaris Dermatologica 165:627–635, 1982 Idiopathic follicular hyperkeratotic spicules of the nose JAAD 36:476–477, 1997

Hyperkeratotic Lesions Junctional epidermolysis bullosa of late onset(formerly junctional epidermolysis bullosa progressive) – loss of dermatoglyphs, waxy hyperkeratosis of dorsal hand, atrophic skin of lower leg, transverse ridging and enamel pits of teeth, nail atrophy, amelogenesis imperfect, hyperhidrosis, blisters on elbows, knees, and oral cavity BJD 164:1280–1284, 2011 Keratosis follicularis squamosa of Dohi – scaly 3–10 mm patches symmetrical on trunk and thighs with central brown follicular plugs; margins slightly detached BJD 150:603–605, 2004; Jpn J Dermatol 3:513–514, 1903 Keratosis lichenoides chronica(Nekam’s disease) – reticulated flat-­topped keratotic papules, linear arrays, atrophy, comedo-like lesions, prominent telangiectasia; conjunctival injection, seborrheic dermatitis-­like eruption; acral dermatitis over toes; punctate keratotic papules of palmar creases Ped Derm 26:615–616, 2009; AD 145:867–69, 2009; AD 144:405–410, 2008;JAAD 49:511–513, 2003; Dermatology 201:261–264, 2000; JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; AD 131:609–614, 1995; AD 105:739–743, 1972; Arch Dermatol Syph(Berlin) 31:1–32, 1895; in children JAAD 56:S1–5, 2007 Keratosis punctata Knuckle pads Ped Derm 17:450–452, 2000 Kyrle’s disease(hyperkeratosis follicularis et parafollicularis in cutem penetrans) JAAD 16:117–123, 1987 Lichen planus BJD 142:310–314, 2000; lichen planopilaris – perifollicular hyperkeratosis AD 145:1363–1366, 2009 Lichen sclerosus et atrophicus Lichen striatus J Cutan Pathol 28:65–71, 2001 Micaceous and keratotic pseudoepitheliomatous balanitis JAAD 18:414–422, 1988; Bull Soc Fr Dermatol Syphiligr 68:164–167, 1966 Nagashima type palmoplantar keratoderma – autosomal recessive; transgradiens; acral erythema of palms and soles; hyperkeratosis of elbows and knees and ears; toenail dystrophy; mutation in SERPINB7 BJD 171:847–853, 2014; AD 144:375–379, 2008 Necrolytic acral erythema – serpiginous, verrucous plaques of dorsal aspects of hands, legs; associated with hepatitis C infection JAAD 55:S108–110, 2006; JAAD 50:S121–124, 2004; Int J Derm 35:252–256, 1996; acral velvety hyperpigmented and hyperkeratotic plaques of distal dorsal feet Cutis 84:301–304, 2009 Non-bullous congenital ichthyosiform erythroderma - congenital erythroderma with subsequent generalized scaling; hypertrophic hyperkeratotic lesions BJD 158:1125–1128, 2008 Onychogryphosis JAAD 26:521–531, 1992; acquired; inherited forms – autosomal dominant, congenital forms Palmoplantar keratoderma, including punctuate PPK Periumbilical perforating pseudoxanthoma elasticum JAAD 39:338–344, 1998; JAAD 26:642–644, 1992; AD 115:300–303, 1979 Pityriasis rubra pilaris - including thickened nails Rook p. 2865, 1998, Sixth Edition; juvenile circumscribed pityriasis rubra pilaris – annular red plaques with follicular hyperkeratosis Ped Derm 25:125–126, 2008 Progressive symmetric erythrokeratoderma – buttocks, extensor arms and legs, anterior lower legs Ped Derm 25:633–634, 2008; AD 122:434–440, 1986 Prurigo nodularis – idiopathic or associated with lymphoma, peripheral T-cell lymphoma(Lennert’s lymphoma) Cutis 51:355–358, 1993; Hodgkin’s disease Dermatologica 182:243–246, 1991; Ped Derm 7:136–139, 1990; gluten sensitive enteropathy BJD 95:89–92, 1976; AIDS JAAD 33:837–838, 1995; uremia South Med J

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68:138–141, 1975; depression, liver disease, alpha-1 antitrypsin deficiency Sustralas J Dermatol 32:151–157, 1991; malabsorption Dermatologica 169:211–214, 1984 Pseudo-acanthosis nigricans - personal observation Psoriasis, including rupioid psoriasis – circular concentric layers of scale creating a cone(limpet shell) Cutis 94:119–121, 2014; Cutis 88:135–137, 2011 Reactive perforating collagenosis - personal observation Spiny keratoderma(multiple minute palmar-plantar digitate hyperkeratoses)(music box keratoderma)(punctuate/spiny keratoderma)(filiform hyperkeratosis of the palms)( porokeratosis punctata palmaris et plantaris)(disseminated parakeratotic spiny keratosis)( Palmoplantar orthokeratotic filiform hyperkeratosis; palmoplantar orthokeratotic spiny keratosis; disseminated orthokeratotic filiform hyperkeratosis; disseminated orthokeratotic spiny keratosis; filiform hyperkeratosis in eccrine hamartoma; spiny keratosis in eccrine hamartoma) – spiny, filiform, spiked, minute aggregate JAAD 58:344–348, 2008; AD 144:1051–1056, 2008; AD 142:235–240, 2006; Int J Derm 44:664–667, 2005; Eur J Dermatol 9:460–465, 1999; Cutis 54:389–394, 1994; AD 125:816–819, 1989; BJD 121:239–242, 1989; JAAD 18:431–436, 1988; AD 104:682–683, 1971; AD 96:692–693, 1967; autosomal dominant; may remit with topical 5-fluorouracil; may be associated with autosomal dominant polycystic kidney disease JAAD 34:935–936, 1996; JAAD 26:879– 881, 1992; questionable paraneoplastic associations Dermatology 201:379–380, 2000; digestive adenocarcinoma Ann DV 124:707– 709, 1997; breast cancer Ann DV 117:834–836, 1990 Striate palmoplantar keratoderma – autosomal dominant; hyperkeratosis of knees, intermittent blisters, and hyperhidrosis; mutation in desmoglein-1 BJD 166:36–45, 2012 Symmetrical acrokeratoderma(?acanthosis nigricans) – hyperpigmented hyperkeratotic flexural regions and dorsal hands; wrists, knees, ankles BJD 170:948–951, 2014; JAAD 70:533–538, 2014 Symmetrical interdigital hyperkeratosis of the hands Acta DV 73:459–460, 1993 Terra firme(Diogenes syndrome) – hyperpigmented hyperkeratotic plaques of neck of teenagers and pre-teens Ped Derm 29:297–300, 2012; self-neglect Lancet i:366–368, 1975 Tinea amientacea(pityriasis amiantacia) - personal observation Transient reactive papulotranslucent acrokeratoderma Australas J Dermatol 41:172–174, 2000 Verrucous hyperplasia of the stump(amputee) Dermatitis 19:109– 111, 2008

SYNDROMES Acantholytic ectodermal dysplasia(similar to McGrath syndrome) – curly hair, palmoplantar keratoderma, skin fragility, hyperkeratotic fissured plaques with perioral involvement, red fissured lips, nail dystrophy BJD 160:868–874, 2009 AKT1 somatic mosaicism – hemihypertrophy, hemimacroglossia, epidermal nevus, café au lait macules BJD 175:612–614, 2016 Apert’s syndrome – circumferential nail at tip of fused digits Bafverstedt syndrome – linear horny excrescences of face and neck; mental retardation, seizures Acta DV 22:207–212, 1941 Bannayan-Riley-Ruvalcaba-Zonana syndrome(PTEN phosphatase and tensin homolog hamartoma) – acral keratoses; facial verrucous papules, angiokeratomas; dolicocephaly, frontal bossing, macrocephaly, ocular hypertelorism, long philtrum, thin upper lip, broad mouth, relative micrognathia, lipomas, penile or vulvar lentigines, facial verruca-like or acanthosis nigricans-like papules, multiple

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acrochordons, angiokeratomas, transverse palmar crease, accessory nipple, syndactyly, brachydactyly, vascular malformations, arteriovenous malformations, lymphangiokeratoma, goiter, hamartomatous intestinal polyposis JAAD 53:639–643, 2005; AD 132:1214–1218, 1996 Bloom’s syndrome – increased risk of squamous cell carcinoma JAAD 74:437–451, 2016 CHILD syndrome – X-linked dominant; linear hyperkeratosis with brownish scaling of fingers and toes AD 142:348–351, 2006; linear hyperkeratotic plaques of feet(unilateral inflammatory ichthyosiform nevus)with spontaneous involution; strawberry-like papillomatous lesions of toes; macrodactyly; ptychotropism, shortening and absence of limbs, short stature; ipsilateral involvement of bones, lung, kidney, heart, brain; epiphyseal stippling(chondrodysplasia punctata); short stature, scoliosis, clefting of hand or foot, hexadactyly; lateralization and mutations in NSDHL gene which encodes 3-beta hydroxysteroid dehydrogenase JAAD 63:1–22, 2010; BJD 161:714–715, 2009 CHILD syndrome without congenital hemidysplasia – extensive lentigo simplex, linear epidermolytic nevus, and epidermolytic nevus comedonicus; mutation in KRT10 BJD 173:293–296, 2015 Clouston’s syndrome – mild sensorineural hearing loss, alopecia, thick dystrophic nail plates, palmoplantar keratoderma, photophobia; mutation in GJB2 and GJB6 JAMA Derm 149:1350–1351, 2013 CLOVE syndrome – capillary, venous, and mixed vascular malformations, epidermal nevi, congenital lipomatous overgrowth; hemihypertrophy(milder than that of Proteus syndrome); ballooning of big toes, symmetrically overgrown feet; wrinkling of palms and soles; severe central nervous system involvement Ped Derm 27:311–312, 2010; Am J Med Genet 143A:2944–2958, 2007 Congenital malalignment of the great toenail - thickened nails Corneal changes, hyperkeratosis, short stature, brachydactyly, premature birth – autosomal dominant Am J Med Genet 18:67–77, 1984 Costello syndrome – warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet, thick palmoplantar surfaces, hypoplastic nails, short stature, craniofacial abnormalities Eur J Dermatol 9:533–536, 1999; Aust Paediat J 13:114–118, 1977 Cowden’s disease - Type 2 segmental Cowden’s disease – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi(including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of limbs, ballooning of toes, bowel polyps, ­glomerulosclerosis, macropcephaly BJD 156:1089–1090, 2007; Eur J Dermatol 17:133–136, 2007 Deletion of long arm of chromosome 6 – circumferential nail Chanarin-Dorfman disease – neutral lipid storage disease; autosomal recessive; ichthyosiform erythroderma; hyperkeratosis of palms and soles, elbows, knees, ankles; acylglycerol recycling defect; ABHD5 mutation; a necessary cofactor for adipose triglyceride lipase-mediated lipolysis; hepatomegaly, ataxia, neurosensory hearing loss, cataracts, nystagmus, short stature, leukocytes with lipid vacuoles(Jordan’s anomaly) Ped Derm 25:326–331, 2008; BJD 158:1378–1380, 2008 Dowling-Degos syndrome(reticulated pigmented anomaly of the flexures) – seborrheic keratosis-like lesions BJD 147:568–571, 2002 Dyskeratosis benigna intraepithelialis mucosae et cutis hereditaria – conjunctivitis, umbilicated keratotic nodules of scrotum, buttocks, trunk; palmoplantar verruca-like lesions, leukoplakia of buccal mucosa, hypertrophic gingivitis, tooth loss J Cutan Pathol 5:105– 115, 1978

Ectodermal defects - including thickened nails Rook p. 2865, 1998, Sixth Edition Ectodermal dysplasia/skin fragility syndrome – autosomal recessive(Carvajal-Huerta syndrome); autosomal dominant; skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene(encoding plakophilin 1) or DSP(encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 166:36–45, 2012; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Epidermal nevus syndrome – mosaic R248C mutation in FGFR3 JAAD 63:1–22, 2010 Epidermodysplasia verruciformis – spiny hyperkeratosis of palms and soles Ped Derm 20:176–178, 2003; Int J Derm 37:766–771, 1998; giant cobblestoning of palms BJD 155:218–220, 2006 FGFR3 epidermal nevus syndrome – mosaic form of thanatophoric dysplasia; mosaic R248C mutation Am J Med Genet 146A:2275– 2279, 2008 Garcia-Hafner-Happle syndrome – fibroblast growth factor receptor 3 epidermal nevus syndrome BJD 166:202–204, 2012 Gobello syndrome –systematized linear velvety orthokeratotic nevus, hypertrichosis and follicular hyperkeratosis, bony defects with hemihypoplasia of limbs Dermatology 201:51–53, 2000 Greither’s palmoplantar keratoderma – hyperkeratosis of elbows, knees, and shins; mutation in KRT1 Cutis 93:193–198, 2014; JAAD 53:S225–230, 2005 Haim-Munk syndrome – autosomal recessive; mutation in cathepsin C gene(like Papillon-Lefevre syndrome); palmoplantar keratoderma, scaly red patches on elbows, knees, forearms, shins, atrophic nails, gingivitis with destruction of periodontium, onychogryphosis, arachnodactyly, recurrent pyogenic infections BJD 152:353–356, 2005 Hemophagocytic lymphohistiocytosis – verrucous nodules of the legs; hemophagocytosis of erythrocytes, leukocytes, thrombocytes in bone marrow, spleen, liver, or lymph nodes Ped Derm 23:35–38, 2006 Hereditary (bullous) acrokeratotic poikiloderma of Weary(acrokeratotic poikiloderma)(Kindler’s syndrome?) – autosomal dominant – vesiculopustular eruption of hands and feet in infancy and childhood; extensive dermatitis in childhood, persistent poikiloderma sparing face, scalp and ears, verrucous papules of hands, feet, elbows, and knees AD 103:409–422, 1971; pseudoainhum and sclerotic bands Int J Dermatol 36:529–533, 1997; AD 103:409–422, 1971 Hereditary callosities – blisters at periphery of calluses JAAD 11:409–415, 1984 Hereditary focal transgressive palmoplantar keratoderma – autosomal recessive; hyperkeratotic lichenoid papules of elbows and knees, psoriasiform lesions of scalp and groin, spotty and reticulate hyperpigmentation of face, trunk, and extremities, alopecia of eyebrows and eyelashes BJD 146:490–494, 2002 Hereditary sensory and autonomic neuropathy type I – calluses over metatarsal heads which blister, necrose, and ulcerate Hidrotic ectodermal dysplasia(Clouston syndrome)type 2 – thick nails; scalp hair sparse, fine, pale, and brittle or absent; outer two-thirds of eyebrows; thin eyelashes; GJB6; connexin 30 JID

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127:2713–2725, 2007; Ped Derm 19:226, 2002; Am J Med Genetics 100:164–168, 2001; Nature Genetics 26:142–144, 2000; Can Med Assoc J 21:18–31, 1929; mimicker of pachyonychia congenita – subungual hyperkeratosis JID 121:1035–1038, 2003

1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989

Hoof nail deformity BJD 169:946–948, 2013

Int J Derm 39:203–204, 2000; Ped Derm 14:22–25, 1997; AD 132:1239–1244, 1996

Hystrix-like ichthyosis-deafness syndrome – postnatal erythroderma, generalized spiky and cobblestoned hyperkeratosis, sensorineural deafness, connexin mutation BJD 146:938–942, 2002

Lipoid proteinosis BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002;

Netherton's syndrome - hyperkeratosis of medial buttock

Ichthyosis cerebriformis – keratotic plugs, depressions, thick skin, palmoplantar keratoderma JAAD 58:505–507, 2008

Neu-Laxova syndrome – rudimentary eyelids, polyhydramnios, growth retardation, microcephaly, ichthyosis, thick hyperkeratotic skin Am J Med Genet 43:602–605, 1992

Ichthyosis follicularis with atrichia and photophobia(IFAP syndrome) BJD 142:157–162, 2000; Am J Med Genet 85:365–368, 1999

Nevada syndrome – hystrix-like epidermal nevus, multiple extracutaneous vascular malformations with arterio-venous shunts

Ichthyosis prematurity syndrome(“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; erythrodermic infant with caseous vernix-like desquamation; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine scaling of scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin(thick vernix caseosa-like covering)(hyperkeratotic scalp) neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4(FATP4) JAAD 66:606–616, 2012; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008; hyperkeratotic cobblestoning of back of neck, flexural hyperpigmented follicular hyperkeratosis, intertriginous hyperpigmentation and hyperkeratotic plaques in the adult JAMADerm 152:1055–1058, 2016

JAAD 63:1–22, 2010

Incontinentia pigmenti AD 139:1163–1170, 2003 Keratosis follicularis spinulosa decalvans – X-linked dominant and autosomal dominant; alopecia, xerosis, thickened nails, photophobia, spiny follicular papules(keratosis pilaris), scalp pustules, palmoplantar keratoderma, conjunctivitis; keratosis pilaris, follicular atrophoderma, facial erythema JAAD 58:499–502, 2008; Ped Derm 22:170–174, 2005; Arch Dermatol Syphilol 151:384–387, 1926 Keratosis-ichthyosis-deafness(KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles(palmoplantar keratoderma), ichthyosis with well marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, perioral furrows, leukoplakia, bilateral sensorineural deafness, photophobia with vascularizing keratitis, blindness, hypotrichosis of scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; connexin 26 mutation Ped Derm 27:651–652, 2010; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990; JAAD 23:385–388, 1990; JAAD 19:1124–1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915; hyperkeratotic papules and plaques of face, scalp, trunk, extremities; exaggerated diaper dermatitis; KID syndrome with secondary dermatophytosis - cobblestoned palmoplantar keratoderma with ichthyosiform changes of face AD 148:1199–1204, 2012 KLICK syndrome(keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; Acta DV 77:225–227,

Olmsted syndrome – postauricular hyperkeratosis BJD 174:209– 211, 2016; periorificial hyperkeratosis BJD 136:935–938, 1997; Olmsted syndrome with erythromelalgia – palmoplantar keratoderma with erythromelalgia; mutation in TRFV3 JAMADerm 150:303–306, 2014; Ped Derm 10:376–381, 1993 Pachyonychia congenita – hyperkeratotic papules of knees; thickened nails of hands and feet JAAD 67:680–686, 2012; Ped Derm 28:429–432, 2011; Cutis 84:269–271, 2009; BJD 159:238– 240, 2008 Pachyonychia congenita type II – subungual hyperkeratosis; natal teeth, bushy eyebrows, follicular keratoses, angular cheilitis, unruly hair Ped Derm 36:149–151, 2019; AD 147:1077–1080, 2011; BJD 159:500–501, 2008 Palmoplantar keratoderma and spiky hyperkeratosis – ichthyosis of Curth-Macklin; krt 1 mutation BJD 175:1372–1375, 2016 Papillon-Lefevre syndrome Phakomatosis pigmentokeratotica – coexistence of large nevus sebaceus, epidermal nevus, and speckled lentiginous nevus; multilobulated pink nodules representing connective tissue nevus; seizures, hyperhidrosis, peripheral neuropathy; high incidence of vitamin D-resistant rickets Ped Derm 28:715–719, 2011; JAAD 63:1–22, 2010; Ped Derm 25:76–80, 2008; Arch Surg 43:341–375, 1941 Phakomatosis pigmentovascularis – port wine stain, oculocutaneous(dermal and scleral) melanosis, CNS manifestations; type I – PWS and linear epidermal nevus; type II – PWS and dermal melanocytosis; type III – PWS and nevus spilus; type IV – PWS, dermal melanocytosis, and nevus spilus; types II,III, and IV may also have nevus anemicus Ped Derm 21:642–645, 2004; J Dermatol 26:834–836, 1999; Ped Derm 15:321–323, 1998; Ped Derm 13:33–35, 1996; AD 121:651–653, 1985; Jpn J Dermatol 52:1–3, 1947 Proteus syndrome – soft tissue and bony hypertrophy of hands and feet, hemihypertrophy, exostosis, cranial hyperostosis, visceral hamartomas, lipomas, vascular anomalies, linear epidermal nevi(soft, velvety, and flat), connective tissue nevus, gigantism, mosaic distribution of lesions; cerebriform thickening of palms and soles, capillary, venous, lymphatic and combined slow-flow malformations(like Klippel-Trenaunay syndrome); mosaic distribution, progressive course, sporadic occurrence; bilateral ovarian cystadenomas, parotid monomorphic adenoma, lipomas, vascular malformations, lung cysts, facial phenotype; mental retardation, seizures, overgrowth of spleen, thymus, macrodactyly JAAD 56:541–564, 2007; BJD 156:1089–1090, 2007; Eur J Hum Genet 14:1151–1157, 2006; Am J Med Genet C Semin Med Genet 137:38–52, 2005; Am J Med Genet 84:389–395, 1999; Eur J Pediatr 140:5–12, 1983; Birth Defects Orig Artic Ser 15:291–296, 1979; epidermal nevi of trunk and neck, vascular malformations, lipomas, cerebriform connective tissue nevi of feet JAAD 52:834–838, 2005

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  Differential diagnosis:   Klippel-Trenaunay syndrome    Neurofibromatosis type 1    Hemihyperplasia with lipomatosis   Type 2 segmental Cowden’s disease – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi(including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of limbs, ballooning of toes, bowel polyps, glomerulosclerosis, macrocephaly BJD 156:1089–1090, 2007; Eur J Dermatol 17:133–136, 2007   CLOVE syndrome – congenital lipomatous overgrowth, vascular malformation and epidermal nevus

and IgE, normal IgG; mutation in WAS protein JAAD 66:292–311, 2012

Pseudohypoparathyroidism – dry, scaly, hyperkeratotic puffy skin; multiple subcutaneous osteomas, collagenoma BJD 143:1122– 1124, 2000

Amputation stump frictional callosity(lenticular button) or follicular hyperkeratosis

Reactive arthritis syndrome – keratoderma blenorrhagicum; soles, pretibial areas, dorsal toes, feet, fingers, hands, nails, scalp Rev Inst Med Trop Sao Paolo 52:279–280, 2010; Cutis 71:198–200, 2003; Dermatologica 170:77–79, 1985; Semin Arthritis Rheum 3:253–286, 1974 Rothmund-Thomson syndrome(poikiloderma congenitale) – autosomal recessive; hyperkeratotic lesions of hands, wrists, feet, and ankles JAAD 75:855–870, 2016; JAAD 74:437–451, 2016; Ped Derm 18:210–212, 2001; Am J Med Genet 22:102:11–17, 2001; Ped Derm 18:210212, 2001; Ped Derm 16:59–61, 1999; Dermatol Clin 13:143–150, 1995; JAAD 27:75–762, 1992; JAAD 17:332–338, 1987 Schwachman’s syndrome – neutropenia, malabsorption, failure to thrive; generalized xerosis, follicular hyperkeratosis, widespread dermatitis, palmoplantar hyperkeratosis Ped Derm 9:57–61, 1992; Arch Dis Child 55:531–547, 1980; J Pediatr 65:645–663, 1964 Sjogren-Larsson syndrome – autosomal recessive; ichthyosis at birth; hyperkeratotic scale of umbilicus, flexures, palms and soles; thickened red skin with accentuated flexural skin markings, palmoplantar keratoderma; spastic diplegia, tetraplegia, mental retardation; fatty aldehyde dehydrogenase Ped Derm 22:569–571, 2005; Dermatology 193:77–82, 1996; Semin Dermatol 12:210–218, 1993 SOLAMEN syndrome(segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus) Eur J Hum Genet 15:767–773, 2007 Somatic mosaic RASopathy – epidermal nevi with cutaneous hypophosphatemia syndrome; FGF-R3(phosphatonin); Blaschkoesque epidermal nevi JAAD 75:420–427, 2016 Tuberous sclerosis – white epidermal nevi at birth Ped Derm 31:360–362, 2014; Ped Derm 10:16–18, 1993 Werner's syndrome – hyperkeratosis over elbows and knees which ulcerate AD 124:90–101, 1988; increased risk of squamous cell carcinoma JAAD 74:437–451, 2016 WHIM syndrome – warts, hypogammaglobulinema, infections, myelokathexis; abscesses, sinusitis, otitis media, pneumonia; chronic neutropenia; mutation in chemokine receptor CXCR4 family gene JAAD 66:292–311, 2012; Curr Opin Hematol 16:20–26, 2009; Ped Derm 26:155–158, 2009; AD 144:366–372, 2008; Nat Genet 34:70–74, 2003; J Biol Chem 276:42826–42833, 2001 WILD syndrome – disseminated warts, diminished cell-mediated immunity, primary lymphedema, anogenital dysplasia; perianal hypertrophic plaque JAAD 66:292–311, 2012; AD 144:366–372, 2008 Wiskott-Aldrich syndrome – X-linked recessive; thrombocytopenia, pyogenic infections; atopic dermatitis; decreased IgM, increased IgA

TOXINS Arsenical keratoses – workplace exposure or ingestion of contaminated water; keratotic lesions with church spire pattern Actas Dermo-­Sililiograficas 108:781–782, 2017; Environ Health Perspect 107:687–689, 1999

TRAUMA

Chewing callosities in children(“gnaw warts”)- pseudo-knuckle pads(“chewing pads”); obsessive compulsive disorder Turk J Ped 45:348–349, 2003 Frictional callosities; mousing callus of wrist JAAD 55:358–359, 2006; frictional hyperkeratosis - personal observation Malleolar clavus - personal observation Occupational callosities Practitioner 210:507–512, 1973 Physical trauma - onychauxis(hypertrophy of nail) Radiation dermatitis, acute or chronic - keratoses JAAD 54:28–46, 2006 Thermal keratoses JAAD 47:524–529, 2002

VASCULAR DISORDERS Angiokeratoma - isolated lesion; associated with fucosidosis type II, galactosidosis type II, Kanzaki disease, aspartylglycosaminuria, sialidosis type II, adult onset gangliosidosis, beta mannosidase deficiency JAAD 37:523–549, 1997 Cerebral cavernous malformations(cutaneous hyperkeratotic capillary-­venous malformation associated with familial cerebral cavernous malformations)(familial cerebral cavernomas) type 1 – autosomal dominant; localized dark red hyperkeratotic plaques; violaceous to blue-black plaques(malformations); red blanchable patches; red hyperkeratotic plaques; deep blue nodules; cutaneous venous malformations; mutations in CCM-1 gene which encodes for Krev-1 interaction TRAP 1 protein(KRIT1) Ped Derm 26:666–667, 2009; JAAD 56:541–564, 2007; BJD 157:210–212, 2007; Hum Molec Genet 9:1351–1355, 2000; Ann Neurol 45:250–254, 1999; Lancet 352:1892–1897, 1998; CCM2- malcaverin protein; CCM3 – PDCD10 protein Familial cutaneo-cerebral capillary malformations – hyperkeratotic cutaneous vascular malformations Hum Molec Genet 9:1351–1355, 2000; Ann Neurol 45:250–254, 1999 Glomuvenous malformation(plaque-type glomus tumor) – blue macules, papules, plaques; may be hyperkeratotic; mutation in glomulin gene(GLMN) Ped Derm 26:70–74, 2009; Ped Derm 25:381–382, 2008; JAAD 58:S92–93, 2008; BJD 154:450–452, 2006; Ped Derm 18:223–226, 2001; AD 132:704–705, 707–708, 1996; Lyon Chir 21:257–280, 1924; blue-purple nodules with pebbly surface JAAD 56:353–370, 2007; congenital plaque type glomuvenous malformation – may resemble capillary malformation(red patch), venous malformation, or blue nevus JAAD 56:353–370, 2007; familial GVM Bull Soc Fr Dermatol Syphiligr 43:736–740, 1936; hyperkeratotic AD 140:971–976, 2004 Hyperkeratotic capillary-venous malformations(dark red irregularly shaped) associated with cerebral cavernous malformation – KRIT1 mutations Ped Derm 23:208–215, 2006

Hyperkeratotic Lesions of Feet 489 Lymphangioma circumscriptum

DRUG REACTIONS

Lymphostasis verrucosa cutis(chronic lymphedema, multiple causes) – brawny edema with overlying hyperkeratosis

Adalimumab – palmoplantar pustulosis with dystrophic hyperkeratotic 20 nail dystrophy J Drugs Dermatol 12:16–17, 2013

Spindle cell hemangioendothelioma – hyperkeratotic nodules of soles BJD 142:1238–1239, 2000 Verrucous hemangioma – hyperkeratotic plaque; behaves like vascular malformation Ped Derm 23:208–215, 2006; linear along Blaschko's lines JAAD 42:516–518, 2000; keratotic blue plaque BJD 171:466–473, 2014

HYPERKERATOTIC LESIONS OF FEET  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Autoimmune progesterone dermatitis Autosomal dominant chronic mucocutaneous candidiasis NEJM 365:54–61, 2011 Bullous pemphigoid - dyshidrosiform pemphigoid; pemphigoid nodularis JAAD 27:863–867, 1992; AD 118:937–939, 1982 DOCK8 deficiency syndrome(dedicator of cytokinesis 8 gene)(aka autosomal recessive hyper-IgE syndrome)DOCK8 – involved in T cell polarization and activation; atypical guanine exchange factor; interacts with Rho GTPases(CDC42 AND RAC) which mediate actin cytoskeletal reorganization; hematologic stem cell homing and mobilization – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; red papules of neck – molluscum contagiosum; warts, widespread dermatitis(atopic dermatitislike(24% at birth; Job’s 81% dermatitis at birth), asthma, cutaneous staphylococcal abscesses; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation AD 148:79– 84, 2012 Pemphigus vulgaris Lupus erythematosus, hyperkeratotic Acta DV 98:475–476, 2018 Pemphigus vulgaris Ann DV 140:116–119, 2013

CONGENITAL LESIONS Congenital mucinous eccrine nevi – red-brown hyperkeratotic plaques over ankle, foot, and toes AD 148:140–142, 2012

Cabozantinib – VEGFR2 inhibitor; c-met; RET multitargets; tyrosine kinase inhibitor; hand foot skin reactions with bullae, hyperkeratosis, acral erythema; skin and hair depigmentation, splinter hemorrhages, xerosis, red scrotum JAMADerm 151:170–177, 2015 Dabrafenib – keratoacanthomas; plantar calluses, seborrheic keratosis, acneiform eruptions, epidermoid cysts, alopecia, verruca vulgaris BJD 167:1153–1160, 2012; hand-foot skin reactions – thick yellow hyperkeratotic plaques of soles with erythematous borders JAMADerm 151:1103–1109, 2015; JAMADerm 151:102–103, 2015 Dovitinib(selective pan-FGF-R inhibitor) – onycholysis, trichomegaly, straightening of scalp hair, hyperkeratosis of heels, xerostomia JAMADerm 153:723–725, 2017 Lucitinib(selective pan-FGF-R inhibitor) – onycholysis, trichomegaly, straightening of scalp hair, hyperkeratosis of heels, xerostomia JAMADerm 153:723–725, 2017 Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015 RAF inhibitors(MAPK pathway) – vemurafenib and dabrafenib – exanthema warts and other hyperkeratotic lesions, keratoacanthomas, squamous cell carcinoma, melanocytic nevi, keratosis pilaris, seborrheic dermatitis, hyperkeratotic hand-foot reactions, photosensitivity, panniculitis with arthralgias, alopecia JAAD 72:221–236, 2015 Sorafenib(multikinase inhibitor) – hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of feet, hyperkeratotic plaque or blister of feet, red patches on pressure points, red swollen fingertips, gray blisters of fingerwebs, angular cheilitis, perianal dermatitis JAAD 58:545–570, 2008; BJD 158:592–596, 2008 Sunitinib(multikinase inhibitor) – acral erythema with hyperkeratotic plaques JAAD 58:545–570, 2008 Vemurafenib – cystic lesions of face, keratosis pilaris-like eruptions, seborrheic dermatitis rashes, painful hyperkeratosis of soles, squamous cell carcinoma, morbilliform eruptions BJD 173:1024– 1031, 2015; JAMADerm 151:1103–1109, 2015; AD 148:357–361, 2012; palmoplantar hyperkeratosis JAAD 67:1265–1272, 2012

EXOGENOUS AGENTS Foreign body - hair - granuloma of heel

Ectopic nail with polydactyly JAAD 53:1092–1093, 2005 Ichthyosis prematurity syndrome – autosomal recessive; premature birth, ichthyosis, scaly erythroderma, neonatal asphyxia; hyperkeratotic thick caseous lesions of hands, feet, and scalp; eosinophilia; Norway and Sweden; mutation in fatty acid transport protein 4(FATP4) Ped Derm 31:517–518, 2014; AD 147:750–752, 2011

DEGENERATIVE DISEASES Disuse hyperkeratosis – of toes in paraplegic BJD 163:646–648, 2010 Neurotrophic ulcers including those associated with neuropathies – begins as fissured callosity on metatarsal heads and heels

INFECTIONS Blastomycosis-like pyoderma(pyoderma vegetans) - crusted or verrucous plaques which may weep, ulcerate or clear centrally, often involve the flexures, and do not respond to antibiotics alone despite the regular presence of Staph aureus or Group A streptococci JAAD 20:691–693, 1989 Candidal granuloma(CMCC) JAAD 21:1309–1310, 1989; chronic mucocutaneous candidiasis Ann Rev Med 32:491–497, 1981 Chromoblastomycosis - feet, legs, arms, face, and neck; common causative organisms include Phialophora verrucosa, Fonsecaea pedrosoi, F. compactum, Wangiella dermatitidus, and Cladosporium carrionii, and Aureobasidium pullulans; diagnostic characteristic is

490 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 the presence of large pigmented round thick walled bodies with septation in two planes(muriform cells) AD 133:1027–1032, 1997; BJD 96:454–458, 1977; AD 104:476– 485, 1971 Ecthyma - personal observation Erythrasma – disciform erythrasma; intertriginous and perigenital; Corynebacterium minutissimum; red to brown irregularly shaped and sharply marginated scaly and slightly creased patches of toe webs; coral-red fluorescence with Wood's light examination due to coproporphyrin; toe clefts are most frequent location Rev Infect Dis 4:1220–1235, 1982 Fusarium – immunocompetent farmer Indian J Dermatol 58:159, 2013 Hepatitis C infection – necrolytic acral erythema; psoriasiform, hyperpigmented hyperkeratotic plaques of hands, feet, knees JAAD 63:259–265, 2010; Cutis 81:356–360, 2008; JAAD 55:S108–110, 2006

INFILTRATIVE DISEASES Amyloidosis - lichen amyloidosis Juvenile xanthogranuloma Ped Derm 17:460–462, 2000 Lichen myxedematosus

INFLAMMATORY DISEASES Sarcoidosis Dermatol Online J 18:10, 2012

METABOLIC DISEASES Calcinosis cutis – heel sticks – personal observation Diabetes mellitus – plantar calluses JAAD 70:1–18, 2014; neuropathic hemorrhagic calluses of feet Myxedema – hyperkeratosis of the feet NEJM 372:764, 2015

Herpes zoster in AIDS

Necrobiosis lipoidica diabeticorum

Leprosy

Pellagra Nutrition 29:1426–1428, 2013

Mycobacterium tuberculosis - hematogenous disseminated tuberculosis – annular verrucous plaques of buttocks, scrotal ulcers, hyperkeratotic plaques of sole Clin Inf Dis 49:1402–1404,1450– 1451, 2009

Tyrosinemia Type II – painful calluses AD 130:507–512, 1994

Necrolytic acral erythema – serpiginous, verrucous plaques of dorsal aspects of hands, legs; associated with hepatitis C infection Cutis 98: 16,19–20, 2016; Int J Derm 35:252–256, 2016; JAAD 50:S121–124, 2004; acral hyperkeratotic hyperpigmented plaques with red to violaceous centers Ped Derm 28:701–706, 2011

NEOPLASTIC DISEASES

Osteomyelitis – with painful neuropathic callus; subungual hyperkeratosis resembling onychomycosis AD 147:1330–1332, 2011

Connective tissue nevus - purplish verrucous plantar plaque BJD 146:164–165, 2002

Pinta - tertiary(late phase) – hyperkeratoses of forearms, elbows, knees, ankles, legs, palms and soles

Dermatophytoma of the nail – yellow hyperkeratosis of nail AD 147:1277–1282, 2011

Pitted keratolysis

Eccrine syringofibroadenoma – diffuse unilateral plantar hyperkeratosis BJD 149:885–886, 2003

Scabies, crusted(Norwegian scabies) – hyperkeratotic nodule of instep Ped Derm 27:93–94, 2010; Dermatology 197:306–308, 1998; AD 124:121–126, 1988; crusted scabies mimicking erythrodermic psoriasis with hyperkeratotic feet Ped Derm 31:753–754, 2014; hyperkeratotic psoriasiform dermatitis JAAD 82:533–548, 2020 Syphilis, secondary (clavi syphillitici) JAAD 82:1–145, 2020; tertiary – tabes dorsalis – initial lesion is clavus over weight-bearing regions of soles Arch Neurol 42:606–613, 1985 Tinea pedis – resembling crusted scabies; scutular favus-like tinea pedis - Microsporum gypseum Tungiasis – verrucous plaque BJD 144:118–124, 2001 Warts - giant disseminated verrucosis(HPV2)(giant verrucous claw hands and feet) associated with idiopathic CD4 lymphopenia AD 146:69–73, 2010 Yaws(mother yaw) - Treponema pallidum subsp. pertenue; 10–13 micron long by .15 micron wide; replicate in 30 hours; non-venereal; transmitted by skin contact; primarily in children; primary lesions on feet, legs, and buttocks; crab yaws - Africa, Asia, South and Central America, and Pacific Islands Ped Derm 27:364–367, 2010; JAAD 54:559–578, 2006; JAAD 29:519–535, 1993; Cutis 38:303–305, 1986; tertiary yaws – palmoplantar keratoderma Ped Derm 27:364–367, 2010

Zinc deficiency

Acquired fibrokeratoma of the heel AD 121:386–388, 1985 Bowen's disease - of the foot AD 123:1517–1520, 1987; of both feet BJD 151:227–228, 2004

Epidermal nevus Superficial acral fibromyxoma – red keratotic toe nodule obliterating nail bed Cutis 97:260,281–282, 2016; Hum Pathol 32:704–714, 2016; Am J Surg Pathol 36:789–798, 2016 Fibro-osseous pseudotumor of the digit – hyperkeratotic brown papule of the the toe tip AD 147:975–980, 2011; Cancer 58:2103– 2109, 1986 Kaposi's sarcoma - verrucous nodules and hyperkeratotic Kaposi’s sarcoma in AIDS with massive lymphedema JAAD 59:179–206, 2008; BJD 142:501–505, 2000; JAAD 38:143–175, 1998; anaplastic Kaposi’s sarcoma – yellow hyperkeratotic plantar nodules BJD 164:209–211, 2011; cutaneous horn JAAD 64:447–448, 2011; AD 98:37–40, 1968 Keratoacanthoma Lymphoma – verrucous cutaneous T-cell lymphoma Clin Exp Dermatol 21:205–208, 1996; cutaneous T-cell lymphoma - plantar hyperkeratosis BJD 161:826–830, 2009; annular hyperkeratotic plaques of hands and feet(Woringer Kolopp disease) (pagetoid reticulosis)BJD 163:651–653, 2010; (JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939; hyperkeratotic plaque AD 120:1045–1051, 1984; Sezary syndrome Nevus comedonicus Porokeratosis of Mibelli, linear porokeratosis Seborrheic keratosis Squamous cell carcinoma J Nippon Med Sch 84:105–107, 2017

Hyperkeratotic Lesions of Feet 491 Stucco keratosis Subungual exostosis - hyperkeratotic nodule Ped Derm 13:212– 218, 1996

Ichthyosis en confetti - neonatal ichthyosiform erythroderma, hyperpigmented verrucous and cerebriform plaques of heels and neck BJD 176:249–251, 2017

Verrucous carcinoma – epithelioma cuniculatum NEJM 352:488, 2005; AD 136:547–548, 550–551, 2000; of feet and legs JAAD 56:S2–32, 2007

Ichthyosis vulgaris palmaris et plantaris dominans – form of ichthyosis vulgaris Dermatologica 165:627–635, 1982

Waldenstrom’s macroglobulinemia – cutaneous macroglobulinosis; painful keratotic vascular papules Clin Exp Dermatol 35:278–281, 2010

Keratosis punctata – flexures

PARANEOPLASTIC DISORDERS Necrolytic migratory erythema – glucagonoma syndrome

Keratosis lichenoides chronica JAAD 38:306–309, 1998 Lichen planus – spiny hyperkeratotic papules An Bras Dermatol 90(suppl 1)175–177, 2015 Lichen sclerosus et atrophicus Lichen simplex chronicus Lichen striatus – nail lesion AD 145:1053–1058, 2009 Marginal papular acrokeratodermas Dermatology 203:63–65, 2001

PRIMARY CUTANEOUS DISEASES Acanthosis nigricans Acrodermatitis continua of Hallopeau Acrokeratoelastosis of Costa J Cutan Pathol 25:580–582, 1998; Acta DV 60:149–153, 1980 Acrokeratosis verruciformis of Hopf Dermatol Online J 18:12, 2012 Atopic hand-foot dermatitis; juvenile plantar dermatosis Ped Derm 18:102–106, 2001; Acta DV 58:531–534, 1978 Callus Br Med J 312:1403–1406, 1996; overlying metatarsal heads, sides of arches, heels; over the talus anteromedial to lateral malleolus Clin Exp Dermatol 16:118–120, 1991; hereditary painful callosities; blisters at periphery of calluses JAAD 11:409–415, 1984 Chronic recalcitrant pustular eruption of palms and soles Clavus, plantar or interdigital(between fourth and fifth toes) Clin Orthop 142:103–109, 1979 Darier's disease(keratosis follicularis) - of foot Case Rep Dermatol Med 2013;419797 Dyshidrosis Ectopic plantar nail BJD 149:1071–1074, 2003 Epidermolysis bullosa - alpha6-beta4 epidermolysis bullosa – onychogryphosis; yellow-brown discoloration of teeth with enamel defects BJD 169:115–124, 2013 Epidermolysis bullosa; non-Herlitz junctional epidermolysis bullosa with collagen XVII mutation – palmoplantar callosities JAAD 52:371–373, 2005; AD 122:704–710, 1986; Dermatologica 152:72–86, 1976 Epidermolysis bullosa, epidermolytic type – palmoplantar callosities JAAD 42:1051–1066, 2000 Epidermolysis bullosa pruriginosa(dystrophic epidermolysis bullosa) – hyperkeratosis of the nails, excoriations, lichenification of shins, white papules JAMA Derm 149:727–731, 2013 Epidermolysis bullosa simplex – palmoplantar callosities JAAD 42:1051–1066, 2000 Epidermolysis bullosa - ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013 Erythema elevatum diutinum JAAD 50:652–653, 2004 Erythrokeratoderma variabilis - personal observation Focal acral hyperkeratosis AD 123:1225, 1228, 1987 Hyperkeratosis lenticularis perstans(Flegel’s disease) – spiky papules of dorsal feet Cutis 105: 2020; An Bras Dermatol 86(suppl 1) S76–77, 2011 Ichthyosis bullosa of Siemens

Palmoplantar keratoderma diffuse or focal - personal observation Palmoplantar pustulosis Pityriasis rubra pilaris Progressive symmetric erythrokeratoderma AD 122:434–440, 1986 Porokeratotic palmoplantar keratoderma discreta Clin Exp Dermatol 21:451–453, 1996; JAAD 10:679–682, 1984; Cutis 20:711–713, 1977 Prurigo nodularis – idiopathic or associated with lymphoma, peripheral T-cell lymphoma(Lennert’s lymphoma) Cutis 51:355– 358, 1993; Hodgkin’s disease Dermatologica 182:243–246, 1991; Ped Derm 7:136–139, 1990; gluten sensitive enteropathy BJD 95:89–92, 1976; AIDS JAAD 33:837–838, 1995; uremia South Med J 68:138–141, 1975; depression, liver disease, alpha-1 antitrypsin deficiency Australas J Dermatol 32:151–157, 1991; malabsorption Dermatologica 169:211–214, 1984 Psoriasis - personal observation Spiny-filiform hyperkeratosis of palms and soles JAAD 58:344–348, 2008 Spiny hyperkeratosis, Blaschko – somatic mosaicism; mutation in connexin 26(GJB2) Ped Derm 33:322–326, 2016 Spiny keratoderma(multiple minute palmar-plantar digitate hyperkeratoses)(music box keratoderma)(punctuate/spiny keratoderma)(porokeratosis punctata palmaris et plantaris) – spiny, filiform, spiked, minute aggregate JAAD 58:344–348, 2008; Cutis 54:389–394, 1994; BJD 121:239–242, 1989; JAAD 18:431–436, 1988; AD 104:682–683, 1971; autosomal dominant; may remit with topical 5–fluorouracil; may be associated with autosomal dominant polycystic kidney disease JAAD 34:935–936, 1996; JAAD 26:879– 881, 1992; questionable paraneoplastic associations Dermatology 201:379–380, 2000; digestive adenocarcinoma Ann DV 124:707– 709, 1997; breast cancer Ann DV 117:834–836, 1990 Music box spicules –Cutis 54:389–394, 1994; AD 125:816–819, 1989; JAAD 18:431–436, 1988 Terra firme(dermatosis neglecta) AD 135:728–729, 1999 Tylosis

SYNDROMES Cardio-facio-cutanous syndrome – plantar hyperkertosis with malodor CHILD syndrome – linear hyperkeratosis with brownish scaling of fingers and toes J Cut Pathol 41:787–790, 2014; AD 142:348–351, 2006; linear hyperkeratotic plaques of feet(unilateral inflammatory ichthyosiform nevus); ptychotropism, shortening and absence of limbs, short stature mutations in NSDHL gene which encodes

492 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 3-beta hydroxysteroid dehydrogenase BJD 161:714–715, 2009; hyperkeratotic papules of ears, dorsal foot Ped Derm 30:250–252, 2013 Clouston’s syndrome – mild sensorineural hearing loss, alopecia, thick dystrophic nail plates, palmoplantar keratoderma, photophobia; mutation in GJB2 and GJB6 JAMA Derm 149:1350–1351, 2013 Costello syndrome – palmoplantar keratosis and deep creases of hands and feet; warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet, thick palmoplantar surfaces, hypoplastic nails, short stature, craniofacial abnormalities BJD 168:903–904, 2013; Eur J Dermatol 9:533–536, 1999; Aust Paediat J 13:114–118, 1977 Dorfman-Chanarin syndrome(neutral lipid storage disease) – autosomal recessive; ichthyosiform erythroderma; hyperkeratosis of palms and soles, elbows, knees, ankles; acylglycerol recycling defect; mutation in ABHD5 gene Ped Derm 25:326–331, 2008 Down’s syndrome – palmoplantar hyperkeratosis Ped Derm 24:317–320, 2007 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive(Carvajal-Huerta syndrome); autosomal dominant; skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene(encoding plakophilin 1) or DSP(encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 166:36–45, 2012; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Epidermodysplasia verruciformis – spiny hyperkeratosis of palms and soles Ped Derm 20:176–178, 2003 Familial mandibuloacral dysplasia Familial milia and absent dermatoglyphics – digital flexion contractures, webbed toes, palmoplantar hypohidrosis, painful fissured calluses, acral blistering, simian crease JAAD 59:1050–1063, 2008 Greither’s syndrome – poikiloderma of face and extremities; warty keratoses over hands, feet, and legs; plantar keratoderma; normal nails and hair Hautarzt 9:364–369, 1958 Haim-Munk syndrome – autosomal recessive; mutation in cathepsin C gene(like Papillon-Lefevre syndrome); palmoplantar keratoderma, scaly red patches on elbows, knees, forearms, shins, atrophic nails, gingivitis with destruction of periodontium, onychogryphosis, arachnodactyly, recurrent pyogenic infections BJD 152:353–356, 2005 Hereditary (bullous) acrokeratotic poikiloderma of Weary(acrokeratotic poikiloderma)( Kindler’s syndrome?) – autosomal dominant – vesiculopustular eruption of hands and feet in infancy and childhood; extensive dermatitis in childhood, persistent poikiloderma sparing face, scalp and ears, verrucous papules of hands, feet, elbows, and knees AD 103:409–422, 1971; pseudoainhum and sclerotic bands Int J Dermatol 36:529–533, 1997; AD 103:409–422, 1971 Hereditary sensory and autonomic neuropathy type I – calluses over metatarsal heads which blister, necrose, and ulcerate Hidrotic ectodermal dysplasia - subungual hyperkeratosis mimicking pachyonychia congenita JID 121:1035–1038, 2003

Ichthyosis follicularis with atrichia and photophobia(IFAP) – X-linked recessive; linear plantar hyperkeratosis of heels; linear hairless scalp area in female carriers; ichthyosis, atopic dermatitis, alopecia, follicular papules, nail dystrophy, hyperextensible joints, photophobia, cheilitis, growth and psychomotor retardation, recurrent respiratory and skin infections, cryptochidism, muscular hypotonia, skeletal abnormalities, inguinal hernia, congenital aganglionic megacolon, corneal vascularization and blindness; mutation in MBTPS2(membrane bound transcription factor protease, site 2) (zinc metalloprotease) JAAD 64:716–722, 2011; Am J Med Genet 85:365–368, 1999; Ped Derm 26:427–431, 2009; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; Ped Derm 12:195, 1995; AD 125:103–106, 1989; Dermatologica 177:341–347, 1988; Am J Med Genet 85:365–368, 1999; BJD 21:165–189, 1909 Incontinentia pigmenti: progressive persistent verrucous plaques; X-linked dominant. Xp28 or Xp11.21 locations; skin lesions present in 50% at birth and in 90% by 2 weeks of life; dental abnormalities in 2/3 of patients, ocular in 25–35%, and CNS defects in 1/3 JAAD 47:169–187, 2002; AD 124:29–30, 1988; double nail with dorsalization of plantar skin(dorsal dimelia); enlarged digit JAMA Derm 149:762–763, 2013 Kindler syndrome – verrucous keratotic plaque of foot; diffuse atrophy or cigarette paper atrophy of hands; atrophied gingival; atrophic nail plates; Kindler's syndrome – acral blistering at birth; progressive poikiloderma; cigarette paper atrophy of hands and feet(scleroatrophy), atrophied gingiva, photosensitivity BJD 157:1252–1256, 2007; AD 142:1619–1624, 2006; AD 142:620–624, 2006; Ped Derm 23:586–588, 2006; AD 140:939–944, 2004; BJD 144:1284–1286, 2001; JAAD 46:447–450, 2001; AD 132:1487– 1490, 1996; AD 133:1111–1117, 1997; Ped Derm 6:82–90, 1989; Ped Derm 6:91–101, 1989; BJD 66:104–111, 1954 Keratosis-ichthosis-deafness(KID) syndrome – squamous cell carcinoma of heel; hyperkeratotic red tumor of heel BJD 166:455– 457, 2012 Lipoid proteinosis(Urbach-Wiethe disease) - autosomal recessive; yellow verrucous plaques and nodules on extensor surfaces; asymptomatic visceral involvement of multiple organs; extracellular hyaline-like material in dermis; PAS positive and diastase resistant; probably represents glycoproteins and/or proteoglycan complexes BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180– 182, 2003; Hum Molec Genet 11:833–840, 2002; JAAD 39:149– 171, 1998; Ped Derm 14:22–25, 1997; JAAD 21:599–601, 605, 1989 Naxos syndrome - personal observation Olmsted syndrome – painful callosities, fragile hair; trichorrhexis nodosa, pili torti, koilonychias; mutation in TRPV3 gene Ped Derm 35:509–510, 2018   Differential diagnosis:   Clouston syndrome   Haim-Monk syndrome    Mal de Meleda   Pachyonychia congenita   Papillon-Lefevre syndrome    Tyrosinemia type II    Vohwinkel syndrome Pachyonychia congenita - mutation in KRT 6A Ped Derm 36:149– 151, 2019; Ped Derm 33:337–342, 2016; JAAD 67:680–686, 2012; Ped Derm 14:491–493, 1997; hyperkeratotic nails Ped Derm 28:429–432, 2011; Cutis 84:269–271, 2009 Phakomatosis pigmentokeratotica - coexistence of an organoid nevus(epidermal nevus) and a contralateral segmental lentiginous or papular speckled lentiginous nevus Dermatology 194: 77–79, 1997

Hyperkeratotic Lesions of the Hands Reactive arthritis - keratoderma blenorrhagicum Semin Arthritis Rheum 3:253–286, 1974 Richner-Hanhart syndrome(tyrosinemia type II) - autosomal recessive; tyrosine aminotransferase deficiency; chromosome 16q22-q24; painful callosities and palmoplantar keratoderma with circumscribed keratoses, linear hyperkeratotic plaques of soles; bullae may occur; dendritic corneal ulcers, mental retardation; palmoplantar hyperhidrosis; signs include tearing, redness, pain and photophobia progressing to superficial and deep dendritic ulcers; mental retardation; aggregated tonofibril bundles on electron microscopy; crystal structures Ped Derm 23:259–261, 2006; J Pediatr 126:266–269, 1995; AD 130:507–511, 1994; Ann DV 120:139–142, 1993; Dermatol 182:168–171, 1991; AD 126:1342– 1346, 1990; Dermatologica 94:286–308, 1947; Klin Monastbl Augenheilkd 100:580–588, 1938 Rothmund-Thomson syndrome(poikiloderma congenitale) – autosomal recessive; hyperkeratotic lesions of hands, wrists, feet, and ankles Ped Derm 18:210–212, 2001; Am J Med Genet 22:102:11– 17, 2001; Ped Derm 18:210212, 2001; Ped Derm 16:59–61, 1999; Dermatol Clin 13:143–150, 1995; JAAD 27:75–762, 1992; JAAD 17:332–338, 1987 Schwachman’s syndrome – neutropenia, malabsorption, failure to thrive; generalized xerosis, follicular hyperkeratosis, widespread dermatitis, palmoplantar hyperkeratosis Ped Derm 9:57–61, 1992; Arch Dis Child 55:531–547, 1980; J Pediatr 65:645–663, 1964 Werner's syndrome X-linked ichthyosis – cobblestoned hyperkeratotic lesions of dorsal feet Cutis 102:402,414–415, 2018

TOXINS Arsenical keratosis Cut Med Surg 20:67–71, 2016 Foreign body granuloma

TRAUMA Clavus - personal observation Dancers' calluses; prayer marks Dermatol Ther Nov 26, 2019 Mechanical hyperkeratosis of the soles J Dermatol 18:291–294, 1991 Scars – hyperkeratosis of scars in weight-bearing areas Acta Chir Scand 131:269–273, 1966

VASCULAR DISEASES Lymphostasis verrucosa cutis(chronic lymphedema, multiple causes) – brawny edema with overlying hyperkeratosis; elephantiasis verrucosa nostra(nostras verrucosa) - chronic lymphedema – congenital, inherited, acquired; associated with obesity, infection, chronic venous insufficiency; cobblestoning, edema, hyperkeratotic plaques of lower legs and feet JAAD 64:1104–1110, 2011; Cutis 62:77–80, 1998; elephantiasis nostras of penis AD 137:1095–1100, 2001; lymphedema of vulva Arch Pathol Lab Med 124:1697–1699, 2000 Pyogenic granuloma Spindle cell hemangioendothelioma – hyperkeratotic nodules of soles BJD 142:1238–1239, 2000

493

HYPERKERATOTIC LESIONS OF THE  HANDS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis, chronic Anti-synthetase syndrome – mechanics’ hands, Raynaud’s phenomenon, interstitial lung disease, anti-Jo-1 antibody AD 141:779–784, 2005 Autoimmune progesterone dermatitis Bullous pemphigoid - dyshidrosiform pemphigoid; pemphigoid nodularis JAAD 27:863–867, 1992; AD 118:937–939, 1982 Chronic mucocutaneous candidiasis Clin Dermatol 23:68–77, 2005 Common variable immunodeficiency – multiple warts Ped Derm 26:155–158, 2009 Dermatomyositis – hyperkeratotic cuticles AD 110:866–867, 1995; amyopathic dermatomyositis - tender ulcerated hyperkeratotic palmar papules in palmar creases of fingers with central white coloration; dermatomyositis with MDA-5(CADM-40)(melanoma differentiation-­associated gene 5)MDA 5 – RNA-specific helicase; all with interstitial lung disease; ulcers of nail folds, Gottron’s papules, and elbows; these patients demonstrate oral ulcers, hair loss, hand edema, arthritis/arthralgia, diffuse hair loss, punched out ulcers of shoulder or metacarpophalangeal joints, digital necrosis, erythema of elbows and knees(Gottron’s sign), and tender gingiva JAMADerm 152:1157–1158, 2016; JAAD 65:25–34, 2011; dermatomyositis with anti–transcriptional intermediary factor-1gamma antibodies – hypopigmented and telangiectatic patches(red and white patches); palmar hyperkeratotic papules; psoriasiform plaques JAAD 72:449–455, 2015 DOCK8 deficiency syndrome(dedicator of cytokinesis 8 gene)(aka autosomal recessive hyper-IgE syndrome)DOCK8 – involved in T cell polarization and activation; atypical guanine exchange factor; interacts with Rho GTPases(CDC42 AND RAC) which mediate actin cytoskeletal reorganization; hematologic stem cell homing and mobilization – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; red papules of neck – molluscum contagiosum; warts, widespread dermatitis(atopic dermatitislike(24% at birth; Job’s 81% dermatitis at birth), asthma, cutaneous staphylococcal abscesses; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation AD 148:79–84, 2012 Graft vs. host disease – acral keratotic form simulating warts Australas J Dermatol 40:161–163, 1999 Lupus erythematosus – hypertrophic DLE – hyperkeratotic nodule of hand AD 145:479–484, 2009; systemic lupus – psoriasiform and hyperkeratotic plaques of palms and soles BJD 81:186–190,1969; hyperkeratotic and ragged cuticles Mixed connective tissue disease – hyperkeratotic cuticles Pemphigus vulgaris Cutis 35:445–446, 1985 Scleroderma – hyperkeratotic plaques over phalanges containing amyloid Trans St John’s Hosp Dermatol Soc 57:177–180, 1971; hyperkeratotic cuticles

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

CONGENITAL LESIONS Congenital ectopic nail – cutaneous horn of fingertip Ped Derm 30:267–269, 2013; congenital palmar nail syndrome, Pierre-Robin syndrome, ectodermal dysplasia, polydactyly, congenital onychodysplasia

Hepatitis C infection – necrolytic acral erythema; psoriasiform, hyperpigmented hyperkeratotic plaques of hands, feet, knees JAAD 63:259–265, 2010 Mycobacterium terrae – hyperkeratotic plaque and osteomyelitis of fingertip following metal staple puncture BJD 152:727–734, 2005

Ichthyosis prematurity syndrome – autosomal recessive; premature birth, ichthyosis, scaly erythroderma, neonatal asphyxia; hyperkeratotic thick caseous lesions of hands, feet, and scalp; eosinophilia; Norway and Sweden; mutation in fatty acid transport protein 4(FATP4) Ped Derm 31:517–518, 2014; AD 147:750–752, 2011

Mycobacterium tuberculosis - tuberculosis verrucosa cutis Int J Derm 39:856–858, 2000

DRUG-INDUCED

Pyoderma

Adalimumab – palmoplantar pustulosis with dystrophic hyperkeratotic 20 nail dystrophy J Drugs Dermatol 12:16–17, 2013 Cabozantinib – VEGFR2 inhibitor; c-met; RET multitargets; tyrosine kinase inhibitor; hand foot skin reactions with bullae, hyperkeratosis, acral erythema; skin and hair depigmentation, splinter hemorrhages, xerosis, red scrotum JAMADerm 151:170–177, 2015 Ipilimumab – monoclonal antibody to cytotoxic T-lymphocyte antigen 4; dermatomyositis eruption with cuticular hypertrophy, photosensitive rash with knuckle papules JAMADerm 151:195–199, 2015 Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015 Piroxicam-induced dyshidrosis Cutis 35:485–486, 1985 RAF inhibitors(MAPK pathway) – vemurafenib and dabrafenib – exanthem, warts and other hyperkeratotic lesions, keratoacanthomas, squamous cell carcinoma, melanocytic nevi, keratosis pilaris, seborrheic dermatitis, hyperkeratotic hand-foot reactions, photosensitivity, panniculitis with arthralgias, alopecia JAAD 72:221–236, 2015 Sorafenib(multikinase inhibitor) – hyperkeratotic papules of knuckles BJD 161:1045–1051, 2009; hand-foot reactions; facial seborrheic dermatitis, red plaques on sides of feet, hyperkeratotic plaque or blister of feet, red patches on pressure points, red swollen fingertips, gray blisters of fingerwebs, angular cheilitis, perianal dermatitis JAAD 60:299–305, 2009; JAAD 58:545–570, 2008; BJD 158:592– 596, 2008 Sunitinib(multikinase inhibitor) – acral erythema with hyperkeratotic plaques of knuckles BJD 161:1045–1051, 2009; JAAD 58:545–570, 2008 Vemurafenib – palmoplantar hyperkeratosis JAAD 67:1265–1272, 2012

EXOGENOUS AGENTS Cocaine – crack cocaine; palmar and digital hyperkeratosis JAAD 69:135–142, 2013

Onychomycosis – thickened nails Osteomyelitis Pinta - tertiary(late phase) – hyperkeratoses of forearms, elbows, knees, ankles, legs, palms and soles Scabies, crusted(Norwegian scabies) - hyperkeratotic papules of knuckles Cutis 92:193–198, 2013; Ped Derm 27:93–94, 2010; Dermatology 197:306–308, 1998; AD 124:121–126, 1988; thickened nails; crusted scabies in IPEX syndrome(immunodysregulation, polyendocrinopathy, enteropathy, X-linked inheritance) JAAD 56:S48–49, 2007; hyperkeratotic knuckle papules Ped Derm 27:93–94, 2010 Syphilis, secondary - personal observation Warts AD 138:405–410, 2002; giant disseminated verrucosis(HPV2) (giant verrucous claw hands and feet) associated with idiopathic CD4 lymphopenia AD 146:69–73, 2010 Yaws JAAD 54:559–578, 2006

INFLAMMATORY DISEASES Polymyositis - fingertip hyperkeratosis AD 129:1207–1208, 1993 Sarcoid – keratotic lesions of palms resembling psoriasis or syphilis; keratotic spines and palmar pits BJD 95:93–97, 1976

METABOLIC Acromegaly – fingertip hy – onychauxis(hypertrophy of nail) Multiple nutritional deficiencies - personal observation Pellagra Porphyria - erythropoietic protoporphyria Eur J Pediatr 159:719– 725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751– 766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976 Tyrosinemia type II(Richner-Hanhart syndrome) – erosions of palms on thenar and hypothenar eminences, soles, tips of fingers which later become hyperkeratotic JID 73:530–532, 1979 Zinc deficiency(acrodermatitis enteropathica)

NEOPLASTIC Acquired digital fibrokeratoma JAAD 12:816–821, 1985 Actinic keratoses JAAD 37:392–394, 1997 Bowen’s disease - personal observation Epidermal nevus - personal observation Keratoacanthoma

INFECTIONS AND INFESTATIONS Blastomycosis-like pyoderma - personal observation Chronic mucocutaneous candidiasis Clin Dermatol 23:68–77, 2005 Dermatophyte infection – resembling crusted scabies

Leukemia – pagetoid reticulosis of in adult T-cell leukemia – hyperkeratotic plaques of palms and soles JAAD 65:1063–1064, 2011 Lymphoma - cutaneous T-cell lymphoma BJD 136:617–619, 1997; localized Pagetoid reticulosis(Woringer-Kolopp disease) – annular

Hyperkeratotic Lesions of the Hands

495

hyperkeratotic plaques of hands and feet BJD 163:651–653, 2010; BJD 147:806, 2002

Autosomal recessive nail dysplasia – mutation in FZD6 encoding Wnt receptor frizzled 6 BJD 166:1088–1094, 2012

Melanocytic nevus – keratotic melanocytic nevus J Cutan Pathol 27:344–350, 2000

Darier's disease, including hemorrhagic acral Darier’s disease Hautarzt 51:857–861, 2000; onychauxis(hypertrophy of nail)

Melanoma – developing in a palmoplantar keratoderma(Greither’s disease) J Dermatol 22:55–61, 1995; nail dystrophy – in situ amelanotic melanoma AD 146:418–421, 2010

Distal subungual corn – tender acral pigmented keratotic subungual papule BJD 171:69–72, 2014

Nevus comedonicus

Ectopic nail - cutaneous horn JAAD 10:114–116, 1984; usually of palmar aspect of fifth finger

Onychomatricoma – hyperkeratotic nail with black dots AD 147:1117–1118, 2011 Onychopapilloma – V-shaped distal split of nail, longitudinal erythronychia, longitudinal leukonychia, onycholysis, longitudinal melanonychia, splinter hemorrhages, distal subungual hyperkeratotic mass JAAD 74:521–526, 2016 Porokeratosis of Mibelli Porokeratotic eccrine ostial and dermal duct nevus Ped Derm 23:465–466, 2006; J Cutan Pathol 15:393–395, 1988; BJD 101:717–722, 1979 Poroma – acral verrucous papule of fingertip AD 144:1051–1056, 2008 Punctate porokeratosis Seborrheic keratosis Squamous cell carcinoma - HPV 26-associated squamous cell carcinoma of nail beds BJD 157:788–794, 2007; subungual and periungual squamous cell carcinoma BJD 167:1310–1314, 2012; BJD 161:1261–1269, 2009; hyperkeratosis of the nailbed JAAD 69:253–261, 2013 Stucco keratosis

Dyshidrosis(resolving)

Epidermolysis bullosa; non-Herlitz junctional epidermolysis bullosa with collagen XVII mutation – palmoplantar callosities JAAD 52:371–373, 2005; AD 122:704–710, 1986; Dermatologica 152:72–86, 1976; ITGB4-­associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013 Epidermolysis bullosa, dominant dystrophic - personal observation Epidermolysis bullosa, epidermolytic type – palmoplantar callosities JAAD 42:1051–1066, 2000 Epidermolysis bullosa pruriginosa(dystrophic epidermolysis bullosa) – hyperkeratosis of the nails, excoriations, lichenification of shins, white papules JAMADerm 149:727–731, 2013 Epidermolysis bullosa simplex – palmoplantar callosities JAAD 42:1051–1066, 2000 Focal acral hyperkeratosis Dermatol Online J 1:10, 2001; AD 123:1225, 1228, 1987 Hereditary papulotranslucent acrokeratoderma Z Hautkr 60:211– 214, 1985

Trichilemmal horn - palmar cutaneous horn AD 120:386–387, 1984; BJD 100:303–309, 1979

Hyperkeratotic dermatitis of the palms BJD 107:195–201, 1982

Verrucous carcinoma

Ichthyosis bullosa of Siemens

Woringer-Kolopp disease(pagetoid reticulosis) JAAD 59:706–712, 2008; Ann Dermatol Syph 10:945–958, 1939

Ichthyosis vulgaris palmaris et plantaris dominans Dermatologica 165:627–635, 1982

Hoof nail deformity BJD 169:946–948, 2013

Id reaction

PARANEOPLASTIC Acrokeratosis paraneoplastica – hand edema, desquamation of hands; hyperkeratotic and lichenified plaques of hands; vesicles and bullae of hands JAMADerm 151:677–678, 2015 Palmar filiform hyperkeratosis JAAD 33:337–340, 1995 vs. Acanthosis nigricans Arsenical keratoses Lichen nitidus Pitted keratolysis Punctate porokeratosis Verruca vulgaris

PRIMARY CUTANEOUS DISEASE Acanthosis nigricans, acral(acral acanthotic anomaly) – hyperpigmentation of elbows, knees, and knuckles JAAD 5:345–346, 1981 Acrodermatitis continua of Hallopeau Acrokeratoelastoidosis BJD 106:337–344, 1982 Acrokeratosis verruciformis of Hopf Aquagenic syringeal acrokeratoderma JAAD 45:124–126, 2001 Atopic hand-foot dermatitis Ped Derm 18:102–106, 2001

Keratolysis exfoliativa(acquired peeling of the palms) – recurrent Trans St John’s Hosp Dermatol Soc 53:165–167, 1967 Keratosis punctata of the palmar creases Cutis 32:75–76, 1983 Knuckle pads Ped Derm 17:450–452, 2000 Lichen planus BJD 142:310–314, 2000 Lichen sclerosus et atrophicus Lichen simplex chronicus Lichen striatus – subungual hyperkeratosis Ped Derm 33:95–96, 2016 Music box spicules – filiform hyperkeratosis of the palms, spiny keratoderma, porokeratosis punctata palmaris et plantaris, multiple minute digitate hyperkeratoses AD 142:235–240, 2006; Cutis 54:389–394, 1994; AD 125:816–819, 1989; JAAD 18:431–436, 1988 Nail dysplasia – autosomal recessive; mutation in FZD6 BJD 168:422–425, 2013 Necrolytic acral erythema – serpiginous, verrucous plaques of dorsal aspects of hands, legs; associated with hepatitis C infection JAAD 50:S121–124, 2004; Int J Derm 35:252–256, 1996; acral hyperkeratotic hyperpigmented plaques with red to violaceous centers Ped Derm 28:701–706, 2011 Onychogryphosis – acquired; inherited forms – autosomal dominant, congenital forms

496 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Onychoheterotopia – mimics polydactyly; nail tissue growing outside of classic nail unit; congenital or familial; seen in Pierre-Robin syndrome and abnormal long arm chromosome 6 JAAD 64:161– 166, 2011 Palmoplantar keratodermas

Transient reactive papulotranslucent acrokeratoderma Australas J Dermatol 41:172–174, 2000 Tylosis Xerotic dermatitis(winter hand dermatitis)

Pincer nail deformity Pityriasis rubra pilaris – PRP type V – hyperkeratotic scaly patches of dorsal hands, annular brown macules, red patches; CARD14 mutation(caspase recruitment domain family 14) JAMADerm 153:66–70, 2017

PSYCHOCUTANEOUS DISEASES

Porokeratotic palmoplantar keratoderma discreta Clin Exp Dermatol 21:451–453, 1996

SYNDROMES

Bulemia – callosities of the hands Am J Psychiatr 5:655, 1985

Prurigo nodularis – idiopathic or associated with lymphoma, peripheral T-cell lymphoma(Lennert’s lymphoma) Cutis 51:355–358, 1993; Hodgkin’s disease Drmatologica 182:243–246, 1991; Ped Derm 7:136–139, 1990; gluten sensitive enteropathy BJD 95:89–92, 1976; AIDS JAAD 33:837–838, 1995; uremia South Med J 68:138–141, 1975; depression, liver disease, alpha-1 antitrypsin deficiency Australas J Dermatol 32:151–157, 1991; malabsorption

Acro-dermato-ungual-lacrimal-tooth syndrome(ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears hooked nose, sparse hair, hypohidrosis, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene(encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes Ped Derm 27:643–645, 2010; Am J Med Genet 45:642–648, 1993

Dermatologica 169:211–214, 1984

Apert’s syndrome – circumferential nail at tip of fused digits

Psoriasis, including pustular psoriasis NEJM 365:620–628, 2011

Bannayan-Riley-Ruvulcaba syndrome - acral keratoses AD 132:1214–1218, 1996

Progressive symmetric erythrokeratoderma AD 122:434–440, 1986

Punctate porokeratotic keratoderma(spiny keratoderma) – yellow keratotic palmar papules AD 147:609–614, 2011; AD 124:1678– 1682, 1988; JAAD 13:908–912, 1985; Dermatologica 147:206–213, 1973 Pustular eruptions of the palms and soles, chronic recalcitrant including pustular bacterid, acrodermatitis of Hallopeau, pustular psoriasis Spiny-filiform hyperkeratosis of palms and soles JAAD 58:344–348, 2008   Palmoplantar porokeratotic filiform hyperkeratosis   Palmoplantar parakeratotic spiny keratosis   Disseminated porokeratotic filiform hyperkeratosis   Disseminated parakeratotic spiny keratosis   Palmoplantar orthokeratotic filiform hyperkeratosis   Palmoplantar orthokeratotic spiny keratosis   Disseminated orthokeratotic filiform hyperkeratosis   Disseminated orthokeratotic spiny keratosis   Filiform hyperkeratosis in eccrine hamartoma   Spiny keratosis in eccrine hamartoma Spiny hyperkeratosis, Blaschko – somatic mosaicism; mutation in connexin 26(GJB2) Ped Derm 33:322–326, 2016 Spiny keratoderma(multiple minute palmar-plantar digitate hyperkeratoses)(music box keratoderma)(punctuate/spiny keratoderma) – spiny, filiform, spiked, minute aggregate JAAD 58:344– 348, 2008; Cutis 54:389–394, 1994; BJD 121:239–242, 1989; JAAD 18:431–436, 1988; AD 104:682–683, 1971; autosomal dominant; may remit with topical 5-fluorouracil; may be associated with autosomal dominant polycystic kidney disease JAAD 34:935–936, 1996; JAAD 26:879–881, 1992; questionable paraneoplastic associations Dermatology 201:379–380, 2000; digestive adenocarcinoma Ann DV 124:707–709, 1997; breast cancer Ann DV 117:834–836, 1990 Symmetrical acrokeratoderma(?acanthosis nigricans) – hyperpigmented hyperkeratotic flexural regions and dorsal hands; wrists, knees, ankles BJD 170:948–951, 2014; JAAD 70:533–538, 2014 Symmetrical interdigital hyperkeratosis of the hands Acta DV 73:459–460, 1993 Terra firme(Diogenes syndrome) Lancet i:366–368, 1975

CHILD syndrome – linear hyperkeratosis with brownish scaling of fingers and toes AD 142:348–351, 2006 Clouston’s syndrome – mild sensorineural hearing loss, alopecia, thick dystrophic nail plates, palmoplantar keratoderma, photophobia; mutation in GJB2 and GJB6 JAMA Derm 149:1350–1351, 2013 Costello syndrome – Costello syndrome – palmoplantar keratosis and deep creases of hands and feet BJD 168:903–904, 2013; warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet, thick palmoplantar surfaces, hypoplastic nails, short stature, craniofacial abnormalities Eur J Dermatol 9:533–536, 1999; Aust Paediat J 13:114–118, 1977 Cowden’s syndrome – acral keratoses AD 142:625–632, 2006 Deletion of long arm of chromosome 6 – circumferential nail Dorfman-Chanarin syndrome(neutral lipid storage disease) – autosomal recessive; ichthyosiform erythroderma; hyperkeratosis of palms and soles, elbows, knees, ankles; acylglycerol recycling defect; mutation in ABHD5 gene Ped Derm 25:326–331, 2008 Down’s syndrome – palmoplantar hyperkeratosis Ped Derm 24:317–320, 2007 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive(Carvajal-Huerta syndrome); autosomal dominant; skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene(encoding plakophilin 1) or DSP(encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 166:36–45, 2012; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Epidermodysplasia verruciformis – spiny hyperkeratosis of palms and soles Ped Derm 20:176–178, 2003

Hyperkeratotic Papules of the Nipple 497 Familial multiple acral mucinous fibrokeratomas - verrucous papules of the fingers JAAD 38:999–1001, 1998

dermatitis, palmoplantar hyperkeratosis Ped Derm 9:57–61, 1992; Arch Dis Child 55:531–547, 1980; J Pediatr 65:645–663, 1964

Greither’s syndrome – poikiloderma of face and extremities; warty keratoses over hands, feet, and legs; plantar keratoderma; normal nails and hair Hautarzt 9:364–369, 1958

WHIM syndrome – warts, hypoglobulinemia, recurrent bacterial infections, myelokathesis; mutation in chemokine receptor CXCR4 Ped Derm 26:155–158, 2009; Nat Genet 34:70–74, 2003; J Biol Chem 276:42826–42833, 2001

Haim-Munk syndrome – autosomal recessive; mutation in cathepsin C gene(like Papillon-Lefevre syndrome); palmoplantar keratoderma, scaly red patches on elbows, knees, forearms, shins, atrophic nails, gingivitis with destruction of periodontium, onychogryphosis, arachnodactyly, recurrent pyogenic infections BJD 152:353–356, 2005

Woolly hair, premature loss of teeth, nail dystrophy, acral hyperkeratosis, and facial abnormalities BJD 145:157–161, 2001

Hereditary (bullous) acrokeratotic poikiloderma of Weary(acrokeratotic poikiloderma)(Kindler’s syndrome?) – autosomal dominant – vesiculopustular eruption of hands and feet in infancy and childhood; extensive dermatitis in childhood, persistent poikiloderma sparing face, scalp and ears, keratotic verrucous papules of hands, feet, elbows, and knees AD 103:409–422, 1971; pseudoainhum and sclerotic bands Int J Dermatol 36:529–533, 1997; AD 103:409–422, 1971

TOXIN

Hidrotic ectodermal dysplasia(Clouston’s syndrome) – pebbly cobblestoned fingertips; alopecia, thick nails Ped Derm 27:651–652, 2010; subungual hyperkeratosis mimicking pachyonychia congenita JID 121:1035–1038, 2003

Chewing callosities in children(“gnaw warts”)

Hidrotic ectodermal dysplasia(Clouston syndrome)type 2 – thick nails; scalp hair sparse, fine, pale, and brittle or absent; outer two-thirds of eyebrows; thin eyelashes; GJB6; connexin 30 JID 127:2713–2725, 2007; Ped Derm 19:226, 2002; Am J Med Genetics 100:164–168, 2001; Nature Genetics 26:142–144, 2000; Can Med Assoc J 21:18–31, 1929 Kindler's syndrome – acral bullae in infancy; progressive poikiloderma with photosensitivity; nail dystrophy, webbing of digits, esophageal and urethral stenosis, ectropion, poor dentition, gingival fragility, aged hands with fine wrinkling and scarring, hyperkeratosis of hands and palms and soles, dyspigmentation, diffuse telangiectasias, short arm chromosome 20; Kind 1; actin cytoskeleton-extracellular matrix interactions(membrane associated structural and signaling protein AD 142:620–624, 2006 Lipoid proteinosis BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002; Int J Derm 39:203–204, 2000; Ped Derm 14:22–25, 1997; AD 132:1239–1244, 1996 Loricrin keratoderma – honeycomb or non-honeycomb palmoplantar keratoderma, ichthyosis, hyperkeratosis of the dorsal hands BJD 159:714–719, 2008 Mal de Meleda

Arsenical keratosis – personal observation Foreign body granuloma

TRAUMA Callosities; mousing callus of wrist JAAD 55:358–359, 2006 Clavus Ectopic nail - acquired post-traumatic ectopic nail(onychoheterotopia) SKINmed 12:306–307, 2014 Occupational callosities Practitioner 210:507–512, 1973

VASCULAR DISORDERS Angiokeratoma Lymphostasis verrucosa cutis

HYPERKERATOTIC PAPULES OF THE  NIPPLE DRUGS Sorafenib JAAD 71:217–227, 2014 Vemurafenib Clin Exp Dermatol 41:148–151, 2016

NEOPLASTIC DISORDERS Epidermal nevus Paris Med 28:63–66, 1938

Naxos syndrome - personal observation

Florid papillomatosis of the nipple

Pachyonychia congenita – subungual hyperkeratosis; mutation in KRT 6A Ped Derm 33:337–342, 2016; JAAD 67:680–686, 2012; AD 147:1077–1080, 2011; Ped Derm 28:429–432, 2011; BJD 161:139– 145, 2009; Cutis 84:269–271, 2009

Lymphomas, including cutaneous T-cell lymphoma Turk J Ped 56:565–567, 2014; JAAD 41:274–276, 1999; JAAD 37:124–125, 1995 Nevoid hyperkeratosis of the nipple JAAD 46:414–418, 2002; BJD 142:382–384, 2000; JAAD 41:325–326, 1999

Reactive arthritis syndrome – keratoderma blenorrhagicum; soles, pretibial areas, dorsal toes, feet, fingers, hands, nails, scalp Cutis 71:198–200, 2003; Semin Arthritis Rheum 3:253–286, 1974

Paget’s disease of the breast(nipple) Dermatologica 170:170–179, 1985; Surg Gynecol Obstet 123:1010–1014, 1966

Rothmund-Thomson syndrome(poikiloderma congenitale) – autosomal recessive; hyperkeratotic lesions of hands, wrists, feet, and ankles Ped Derm 18:210–212, 2001; Am J Med Genet 22:102:11– 17, 2001; Ped Derm 18:210212, 2001; Ped Derm 16:59–61, 1999; Dermatol Clin 13:143–150, 1995; JAAD 27:75–762, 1992; JAAD 17:332–338, 1987

Squamous cell carcinoma of the nipple Case Rep Pathol 2015:327487

Schwachman’s syndrome – neutropenia, malabsorption, failure to thrive; generalized xerosis, follicular hyperkeratosis, widespread

Seborrheic keratoses

PRIMARY CUTANEOUS DISEASES Acanthosis nigricans JAAD 52:529–530, 2005; JAAD 31:1–19, 1994 Clear cell acanthoma-like lesions JAAD 80:749–755, 2019

498 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Darier's disease Epidermolytic hyperkeratosis – verrucous plaques of nipples Erosive adenomatosis(papillary adenomatosis) of the nipple – blood-­stained or serous discharge; enlarged nipple; eroded nipple; erythema, ulcer, crusted dermatitis, granular appearance, papule on nipple JAAD 47:578–580, 2002; JAAD 43:733–751, 2000; JAAD 12:707–715, 1985 Hyperkeratosis of the nipple and areola(hyperkeratosis areolae mammae) AD 137:1327–1328, 2001; JAAD 41:274–276, 1999; Eur J Dermatol 8:131–132, 1998; AD 126:687, 1990; JAAD 13:596–598, 1985; estrogen-induced Cutis 26:95–96, 1980; associated with CTCL JAAD 32:124–125, 1995; Int J Derm 29:519–520, 1990; ichthyosis, ichthyosiform erythroderma, acanthosis nigricans, Darier’s disease; in pregnancy JAMADerm 149:722–726, 2013 Ichthyosiform erythrodermas Ichthyosis Lichen sclerosus et atrophicus Lichen simplex chronicus Perforating pseudoxanthoma elasticum An Bras Dermatol 85:705– 707, 2010 Psoriasis Terra firme(neglected nipples) Indian J DV Leprol 85:169–170, 2019; Dermatol Pract Concepts 31:81–84, 2014

SYNDROMES Keratosis-ichthyosis-deafness(KID) syndrome - acanthosis nigricans-like change of the nipple AD 123:777–782, 1987; hypoplasia of nipples Ped Derm 19:513–516, 2002

HYPERPIGMENTATION IN BLASCHKO’S LINES JAAD 31:157–190, 1994; J Pediatr 116:581–586, 1990

AUTOIMMUNE DISEASES Morphea/lichen sclerosus overlap - hyperpigmented white scaly Blaschko-esque plaques AD 147:857–862, 2011 Scleroderma - linear scleroderma (en coup de sabre) JAAD 38:366–368, 1998

Melanocytic nevi, café-au-lait macules, and nevi spili Acta DV 78:378–380, 1998 Multiple deep penetrating nevi AD 139:1608–1610, 2003 Nevus comedonicus – areas of hyperpigmentation AD 116:1048– 1050, 1980 Porokeratosis, linear AD 142:1059–1064, 2006; AD 135:1544–1555, 1547–1548, 1999; Ped Derm 4:209, 1987; AD 109:526–528, 1974

PRIMARY CUTANEOUS DISEASES Blaschkitis Lichen planus J Clin Diagn Res 11:WRO1–WR04, 2017 Linear and whorled nevoid hypermelanosis Ped Derm 10:156–158, 1993; JAAD 19:1037–1044, 1988 Linear atrophoderma of Moulin – acquired atrophic pigmented band-like lesions following Blaschko’s lines JAAD 65:232–233, 2011; Eur J Dermatol 10:611–613, 2000; Int J Dermatol 39:850– 852, 2000; JAAD 38:366–368, 1998; BJD 135:277–279, 1996; Ann DV 119:729–736, 1992

SYNDROMES Chondrodysplasia punctata(X-linked variant) Ped Derm 13:1–4, 1996 Chromosome X-autosome translocation Goltz’s syndrome Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia , coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Incontinentia pigmenti - third stage Ped Derm 15:108–111, 1998; Curr Prob in Derm VII:143–198, 1995; AD 112:535–542, 1976 McCune-Albright syndrome – melanotic macules BJD 130:215–220, 1994 Mosaic 13q11 deletion Mosaic tetrasomy 12p

INFILTRATIVE DISORDERS Cutaneous amyloidosis, Partington type(X-linked reticulate pigmentary disorder)

Mosaic 15;22 Mosaic trisomy 18 Mosaic Turner’s syndrome – Blaschko-distributed hyperpigmented macules BJD 175:1379–1381, 2016 Mosaicism/chimerism

NEOPLASTIC DISORDERS Acquired dermal melanocytosis(acquired nevus of Ota-like macules) JAAD 43:934–936, 2000 Basaloid follicular hamartoma Congenital Becker’s nevus Cutis 75:122–124, 2005 Epidermal nevus - early stage Linear lentiginous nevus Clin Exp Derm 40:231–237, 2015

Nevoid basal cell carcinoma syndrome(Gorlin’s syndrome) – autosomal dominant; basal cell carcinomas, basaloid follicular hamartomas, linear hyp- or hyperpigmented lesions; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microph-

Hyperpigmentation, Diffuse 499 thalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors(fibromas), mesenteric cysts, cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism, BJD 182:212–217, 2020; BJD 165:30–34, 2011; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908– 912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004 Ring 10;45 Ring X/46 Ring X+ring Tetragametic chimerism(“cutis bicolor”) – hyper- and hypopigmentation(Blaschko) AD 144:327–330, 2008 Trisomy 14 – partial trisomy 14p Annual Meeting AAD 2000 X-linked reticulate pigmentary disorder(female carriers) Am J Med Genet A 161A:1414–1420, 2013

ACTH administration Adriamycin Amiodarone Argyria – slate-gray pigmentation of sun-exposed areas(forehead, nose, hands); entire skin may be hyperpigmented NEJM 351:2349– 2350, 2004; Am J Kidney Dis 37:1048–1051, 2001; BJD 104:19–26, 1981; AD 114:373–377, 1978 Arsenic – brown diffuse macular hyperpigmentation Atabrine(mepacrine) – greenish-yellow pigmentation of face, hands, feet; then diffuse Am J Med Sci 192:645–650, 1936 Bismuth - generalized hyperpigmentation resembling argyria and/or blue-black line at the gingival margin JAAD 39:524–525, 1998; JAAD 37:489–490, 1997 Bleomycin AD 107:553–555, 1973 Busulfan – diffuse JAAD 9:645–663, 1983; Addisonian Arch Int Med 124:66–71, 1969 Carotenemia – orange skin Clin Derm 37:516–519, 2019 Chemotherapy JAAD 40:367–398, 1999

HYPERPIGMENTATION, DIFFUSE  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Dermatomyositis Graft vs. host reaction, chronic AD 134:602–612, 1998 Lichen planus pemphigoides - personal observation Lupus erythematosus, systemic Morphea – generalized deep morphea JAMADerm 152:1170–1172, 2016; generalized morphea – diffuse hyperpigmentation Pemphigus foliaceus Rheumatoid arthritis Scleroderma(progressive systemic sclerosis) - diffuse cutaneous form; CREST syndrome, morphea Still’s disease

Chemotherapy for acute lymphoblastic leukemia – porphyria cutanea tarda J Drugs Dermatol 13:489–490, 2014 Chloramphenicol overdose in infants - grey baby syndrome Clin Pediatr 21:571–572, 1982 Chloroquine Chlorpromazine Chrysiasis Clofazimine – orange-red hyperpigmentation JAAD 23:236–241, 1990 Cyclophosphamide Dactinomycin Dasatinib J Clin Diagn Res 8:QDO1–2. 2014 Daunorubicin JAAD 46:S1–3, 2002; JAAD 26:255–256, 1992 5-fluorouracil Hydantoin Hydroxychloroquine Hydroxyurea JAAD 49:339–341, 2003; AD 135:818–820, 1999; JAAD 36:178–182, 1997; AD 111:183–187, 1975

CONGENITAL GENERALIZED HYPERPIGMENTATION Adrenoleukodystrophy (Siemerling-Creutzfeld disease) Am J Hum Genet 27:547–553, 1975; X-linked adrenoleukodystrophy BJD 182:239–240, 2020 Carbon baby syndrome – universal acquired melanosis - entire skin deep black Ped Derm 31:620–622, 2014; AD 114:775–778, 1978 Congenital adrenal hyperplasia - congenital generalized hyperpigmentation JAAD 33:323–326, 1995

Imatinib mesylate(Gleevec)(multikinase inhibitor) – skin, hair, and nail pigmentation; repigmentation of gray hair Int J Dermatol 57:784–790, 2018; JAAD 58:545–570, 2008; NEJM 347:446, 2002 Immunosuppressive therapy in transplant recipients – diffuse hyperpigmented xerotic dermatitis JAAD 44:932–939, 2001 Iron – brown pigmentation JAMADerm 150:984–989, 2014 Lichenoid drug eruption Methotrexate

Congenital diffuse pigmentation(Wende-Bauckus)

Minocycline – diffuse hyperpigmentation Arthr Rheum 50:3698– 3701, 2004; JAAD 3:244–247, 1980

Epidermal melanocytosis AD 86:412–418, 1962

MSH administration

Familial pigmentation with nail dystrophy AD 71:591–598, 1955

Nitrogen mustard, topical AD 113:1387–1389, 1977

Familial progressive hyperpigmentation AD 103:581–8, 1971

Oral contraceptives

Green baby - due to intrauterine exposure to Evan's blue dye Am J Perinatol 5:234–235, 1988

Phenolphthalein – diffuse brown pigmentation(fixed drug) Arch Dermatol Syphilol 32:915–921, 1935 Phenothazines, including chlorpromazine AD 90:471–476, 1964

DRUG-INDUCED Cutis 59:77, 1977

Phototoxic and photodynamic drug reactions Polymyxin B, intravenous - personal observation Indian J Pediatr 83:179–180, 2016

500

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Psoralens(PUVA)

INFLAMMATORY DISEASES

Quinidine AD 122:1062–1064, 1986

Eosinophilic fasciitis

Quinine AD 88:419–426, 1963 Rifabutin Silver sulfadiazine cream JAAD 12:1112–1114, 1985 Tetracosactrin BJD 82:389–396, 1970 Thiotepa – diffuse erythema, desquamation, and hyperpigmentation JAAD 58:575–578, 2008 Tigecycline – diffuse hyperpigmentation primarily of face Clin Inf Dis 45:136–137, 2007 Xanthoderma – orange skin Clin in Derm 37:516–519, 2019 Zidovudine JAAD 46:284–293, 2002

EXOGENOUS AGENTS Argyria - homebrew silver solution AD 145:1053–1058, 2009 Heavy metals  Arsenic  Gold  Lead  Mercury  Bismuth Operating room immediate pigmentation - personal observation

INFECTIONS AND INFESTATIONS AIDS/HIV generalized lichenoid hyperpigmentation of AIDS Chronic infection - malaria, kala azar(black sickness, leishmaniasis) J Inf Dis 173:758, 1996, schistosomiasis, tuberculosis Chronic mucocutaneous candidiasis J Clin Endocrinol 16:1374, 1956 Chikungunya fever – in infants, starts with hyperpigmentation of tip of nose(chik sign), ear pinnae, flexures, periorally, then generalizes to entire body; some vesiculobullous lesions JAMADerm 156:99–101, 2020; generalized hypermelanosis JAAD 75:1–16, 2016 Erythrasma Human polyoma virus 6 and 7 – pruritic and dyskeratotic dermatoses – generalized hyperpigmented scaly dermatitis JAAD 76:932– 940, 2017 Leishmaniasis – post kala azar dermal leishmanoid Clin Inf Dis 67:667–675, 2018 Pediculosis – generalized hyperpigmentation JAAD 82:551–569, 2020 Tuberculosis – lupus vulgaris - red-orange plaque Clin Derm 37:516–519, 2019

Sarcoidosis – red-orange plaque Clin Derm 37:516–519, 2019

METABOLIC DISEASES Acromegaly – Addisonian pattern Addison's disease(adrenal insufficiency) – diffuse, slate-like hyperpigmentation, accentuated in flexures, palmar and plantar creases, nipples, genitalia, buccal mucosa, conjunctiva, vagina JAMADerm 150:984–989, 2014; Cutis 76:97–99, 2005; universal melanosis Adrenalectomy - Noonan's syndrome – diffuse hyperpigmentation following bilateral adrenalectomy Asthma melanodermica – prior to attack, diffuse darkening of skin and increase in size and number of nevi AD 78:210–213, 195 Cachectic states Central nervous system disease of diencephalon, substantia nigra – Addisonian pigmentation; after emotional stress Psychosom Med 19:89–98, 1957 Congenital dyschromia with erythrocyte, platelet, and tryptophan metabolism abnormalities JAAD 19:642–655, 1988   vs. Asymmetric mosaics   Congenital leukoderma   Dyschromatosis universalis   Familial progressive hyperpigmentation AD 103:581–598, 1971   Lentiginosis Cushing's disease – Addisonian pattern Ped Derm 15:253–258, 1998 Familial adrenocorticotropin unresponsiveness syndrome(familial glucocorticoid deficiency) J Pediatr Endocrinol Metab 14:1113– 1118, 2001 Folate deficiency AD 112:562, 1976 Gaucher’s disease – glucocerebroside; yellow-brown pigmentation diffuse hyperpigmentation, easy tanning, pigmented macules BJD 111:331–334, 1984 Graves’ disease – Addisonian hyperpigmentation; palms and soles, gingiva, buccal mucosa JAAD 48:641–659, 2003; generalized Medicine 97:e13279, 2018 Hemochromatosis – idiopathic(autosomal recessive) or secondary to chronic iron intoxication(Bantu hemachromatosis), chronic liver disease and iron overload, hepatic hemosiderosis in anemia with ineffective erythropoiesis, congenital transferrin deficiency – bluegray, bronze, gray-brown hyperpigmentation especially of face, flexures, and exposed parts J Drugs in Dermatol 9:719–722, 2010; Clev Clin J Med 76:599–606, 2009; AD 113:161–165, 1977; Medicine 34:381–430, 1955 Hepatic disease, including primary biliary cirrhosis

INFILTRATIVE DISEASES Amyloidosis - macular amyloid; cutis dyschromia Pediatrics May 2017 Juvenile xanthogranuloma – tan-orange papule Clin Derm 37:516– 519, 2019 Langerhans cell histiocytosis - bronze hyperpigmentation Curr Prob in Derm VI:1–24, 1994 Xanthoma disseminatum – orange nodules Clin in Derm 37:516– 519, 2019

Hyperthyroidism – patchy hyperpigmentation or diffuse Addisonian hyperpigmentation sparing oral mucosa; slate-like hyperpigmentation JAMADerm 150:984–989, 2014; JAAD 26:885–902, 1992 Kwashiorkor Liver disease, chronic – diffuse muddy gray hyperpigmentation; primary biliary cirrhosis Lysosomal storage disease – anterior and posterior dermal melanocytosis in Hurler’s disease, GM, gangliosidosis type 1, Niemann-Pick disease, Hunter’s disease, alpha-mannisidosis AD 139:916–920, 2003

Hyperpigmentation, Diffuse 501 Malabsorption – Addisonian hyperpigmentation or local pigmentation of face, neck, trunk Malnutrition Megaloblastic anemia JAAD 12:914–917, 1985 Multiple nutritional deficiencies - personal observation

Neurocutaneous melanosis - personal observation Nevus sebaceus – yellow orange plaque Clin Derm 37:516–519, 2019

Myxedema

Pheochromocytoma – Addisonian pigmentation; generalized Int J Dermatol 43:140–142, 2004

Nelson’s syndrome – post-adrenalectomy diffuse hypermelanosis Ann Int Med 52:560–569, 1960

Thymic carcinoids – Addisonian pigmentation Cancer 71:106–111, 1993

Niemann-Pick disease - acid sphingomyelinase; diffuse pigmentation, especially of face Ochronosis – generalized hyperpigmentation with accentuation over cheeks, forehead, axillae, and genitalia, buccal mucosa, nails Pellagra – niacin deficiency; Addisonian hyperpigmentation; accentuated on face, hands Porphyria – congenital erythropoietic porphyria - blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, keratoconjunctivitis, cataracts JAAD 67:1093– 1110, 2012 Porphyria cutanea tarda – in AIDS Clin Inf Dis 56:851–852, 898–899, 2013; Med Clin NA 64:807–827, 1980’ Am J Med 67:277–286, 1979; variegate porphyria hepatoerythropoietic porphyria AD 116:307–313, 1980 Renal failure, chronic - muddy brown hyperpigmentation Scurvy – Addisonian Sprue Vitamin A deficiency JAAD 41:322–324, 1999 Vitamin B12 deficiency (pernicious anemia) – diffuse or mottled hyperpigmentation of face, hands, feet, and scrotum; Addisonian hyperpigmentation; face, oral mucosa, dorsal hands and feet, periungual hyperpigmentation, knuckles, nail diffuse hyperpigmentation, longitudinal melanonychia, palmar creases Ped Derm 35:796–799, 2018; Cutis 92:94–99, 2013; Cutis 71:127–130, 2003; J Dermatol 28:282–285, 2001; JAAD 15:1263–1274, 1986; AD 12:896–899, 1986; Arch Int Med 145:484–485, 1985; Br Med J 1:1713–1715, 1963; familial vitamin B12 deficiency – inborn error of vitamin B12 metabolism(cblJ mutation) BJD 172:1111–1115, 2015

PARANEOPLASTIC DISORDERS Acanthosis nigricans, generalized Int J Dermatol 52:377–378, 2013 Cachectic state associated with neoplasms Cronkhite-Canada syndrome – colon, gastric cancer Case Rep Gastroenterol 13:109–115, 2018 Ectopic ACTH-producing oat cell carcinoma Arch Int Med 142:1387–1389, 1982 Paraneoplastic Addisonian hyperpigmentation – associated with multiple myeloma J Coll of Physicians and Surgeons Pakistan 21:40–42, 2011 Paraneoplastic corticotropin production Ann Hematol 82:448–451, 2003 Paraneoplastic scleroderma - personal observation

PHOTODERMATOSES Bronze baby syndrome - gray-brown pigmentation after phototherapy for hyperbilirubinemia in neonates; requires liver disease; confused with central cyanosis, carbon baby syndrome, grey baby syndrome JAAD 12:325–328, 1985; Ped Res 17:327–330, 1983; J Pediatr 88:461–464, 1976; JAMA 208:1703, 1969 Phototherapy of neonatal jaundice – darkening of treated areas J Pediatr 82:1042–1043, 1973 Phytophotodermatitis Tanning – immediate and prolonged tanning

Wilson's disease J Neurosci Rural Pract 4:70–72, 2013

PRIMARY CUTANEOUS DISEASES NEOPLASTIC DISEASES

Acanthosis nigricans, generalized Ped Derm 18:213–216, 2001

Acquired generalized lentiginosis

Confluent and reticulated papillomatosis

ACTH and MSH producing tumors(pituitary and others) BJD 126:286–289, 1992

Disseminated dermal melanocytosis BJD 101:197–205, 1979

Carcinoid syndrome – flushing, patchy cyanosis, hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea

Epidermolysis bullosa simplex with mottled pigmentation; may be generalized or of neck, upper trunk, arms and leg with or without keratoderma(punctate keratoses); cutaneous atrophy, nail dystrophy Clin Genet 15:228–238, 1979

Epidermal nevus JAAD 10:1–16, 1984

Human chimerae with pigment anomalies

Extrapituitary neuroendocrine melanoderma

Idiopathic eruptive macular hyperpigmentation Ped Derm 13:274– 277, 1996; JAAD 11:159, 1984

Hodgkin’s disease – Addisonian hyperpigmentation Proc Baylor Univ Med Ctr 32:587–588, 2019 Lymphoma, including cutaneous T-cell lymphoma - diffuse progressive hyperpigmentation JAAD 16:257–260, 1987; CTCL melanoerythroderma Acta DV Croat 27:131–132, 2019; anaplastic large cell lymphoma Ann Saudi Med 32:318–320, 2012

Melanism – autosomal dominant; diffuse hyperpigmentation, especially of face and flexures Bull Acadr Med Belg 13:397–428, 1948 Pityriasis rubra pilaris – reddish-orange Clin Derm 37:520–527, 2019

Melanocytic nevus - giant congenital nevus Melanoma – metastatic; diffuse melanosis; slate gray hyperpigmentation JAAD 68:482–486, 2013; Dermatology 197:338–342, 1998; JAAD 35:295–297, 1996; JAAD 20:261–266, 1989

SYNDROMES

Mongolian spot, generalized J Dermatol 22:330–333, 1995

Berlin syndrome - mottled pigmentation and leukoderma

Acquired generalized lentiginosis Eur J Dermatol 8:183–185, 1998

502 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Breast hypertrophy, erythema annulare centrifugum, generalized melanoderma, verrucae vulgaris and SLE Acta DV(Stockh) 52:33, 1972

hypoplastic anemia, slender build, short broad thumbs, tapered fingers, microcephaly, hypogonadism Semin Hematol 4:233–240, 1967

Costello syndrome – diffuse hyperpigmentation; warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, ­hyperextensible fingers, sparse curly hair, perianal and vulvar papules, generalized hypertrichosis, multiple nevi Am J Med Genet 117:42–48, 2003; Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977

Felty's syndrome

Cronkhite-Canada syndrome – diffuse hyperpigmentation with accentuation of face, neck, extremities, palms and palmar aspects of fingers Ann DV 112:951–958, 1985 Degos-Touraine syndrome – incontinentia pigmenti with poikiloderma in photodistribution, bullae of face, extremities; chronic erythroderma with subsequent hyperpigmentation Soc Gr Dermatol Syph 68:6–10, 1961 Dermatopathia pigmentosa reticularis – generalized reticulate hyperpigmentation, non-cicatricial alopecia, onychodystrophy J Dermatol 24:266–269, 1997 Diffuse pigmentation of trunk and neck with subsequent white macules Proc R Soc Med 48:179–180, 1955 Diffuse pigmentation with macular depigmentation of trunk with reticulate pigmentation of neck Hautarzt 6:458–460, 1955 Dyschromatosis symmetrica hereditaria Clin Exp Dermatol 30:494–496, 2005 Dyschromatosis universalis hereditaria Clin Exp Dermatol 34:e666– 669, 2009; Ann DV 128:136–138, 2001 Dyskeratosis congenita – X-linked recessive; reticulate hyperpigmentation(poikiloderma) of neck, chest, thighs; nail dystrophy, oral, ocular, and anal leukoplakia J Med Genet 25:843– 846, 1988 Elejalde syndrome(neuroectodermal(neurocutaneous)melanolysosomal disease) - silvery hair, bronze colored skin; profound central nervous system dysfunction; hypotonic facies, plagiocephaly, micrognathia, crowded teeth, narrow high palate, pectus excavatum, cryptorchidism; normal immune system; defective transfer of melanosomes JAAD 55:337–340, 2006; AD 135:182–186, 1999; JAAD 38:295–300, 1998 Epidermal melanocytosis - congenital generalized hyperpigmentation AD 86:412–418, 1962 Epidermolysis bullosa herpetiformis with mottled pigmentation and palmoplantar keratoderma AD 122:900–908, 1986 Familial gigantic melanocytosis(familial melanopathy with gigantic melanocytes) – diffuse brown hyperpigmentation with raindrop hypopigmentation, light colored scalp and body hair; sparse pubic and axillary hair; large melanocytes filled with late stage melanosomes Int J Derm 44:1010–1015, 2005; Am J Dermatopathol 6:31–34, 1984 Familial pigmentation with nail dystrophy - congenital generalized hyperpigmentation AD 71:591–598, 1955 Familial progressive hyperpigmentation(congenital generalized hyperpigmentation, hereditary universal melanosis, familial progressive hypermelanosis, melanosis universalis hereditaria) Ped Derm 28:62–65, 2011; AD 125:1442–1443, 1989; AD 103:581–588, 1971; generalized and flexural hyperpigmentation Ped Derm 34:84–89, 2017 Fanconi’s syndrome(pancytopenia with congenital defects) – generalized olive-brown hyperpigmentation, especially of lower trunk, flexures, and neck with depigmented macules(rain drop-like);

Franceschetti-Jadassohn-Naegeli syndrome – generalized reticulated hyperpigmentation, accentuated in neck and axillae; palmoplantar keratoderma; hypohidrosis JAAD 10:1–16, 1984 H syndrome(low height, heart, hallus valgus, hormonal, hypogonadism, hematologic) – histiocytosis with multiorgan involvement, sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; starts on feet and legs and progresses upward; hypertrichosis, short stature, facial telangiectasia, gynecomastia, skeletal deformities(camptodactyly of 5th fingers), scrotal masses with massively edematous scrotum obscuring the penis, gonadotropic hypogonadism with scrotal masses, hyperglycemia, azospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly, mental retardation; hyperpigmentation, hypertrichosis, mutation in nucleoside transporter Hent3, SLC 29A3 Ped Derm 37:333–336, 2020; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008   Differential diagnostic considerations include:   Winchester syndrome – arthropathy, coarse facies, no hearing loss    POEMS syndrome - paraproteinemia Hurler's(MPS I), Hurler-Scheie, Scheie syndromes – generalized hyperpigmentation and thickening of skin Ped Derm 21:154–159, 2004 Incontinentia pigmenti Koraxitrachitic syndrome – self-healing collodion baby with residual dappled atrophy Am J Med Genet 86:454–458, 1999 Lawrence-Seip syndrome(lipoatrophic diabetes) J Dermatol 19:246–249, 1992; Acta DV 66:173–174, 1986 Neurofibromatosis type I – increased generalized background hyperpigmentation JAAD 61:1–14, 2009 Pachyonychia congenita with cutaneous amyloidosis and rippled hyperpigmentation JAAD 16:935–940, 1987 Pachyonychia congenita, Tidman-Wells-MacDonald type Parana hard skin syndrome(stiff skin syndrome) Ped Derm 20:339–341, 2003; Ped Derm 19:67–72, 2002 Phakomatosis pigmentovascularis POEMS syndrome(Crowe-Fukasi syndrome, Takatsuki syndrome)(osteosclerotic myeloma)(PEP syndrome – plasma cell dyscrasia, endocrinopathy, polyneuropathy) – plethora, angiomas(cherry, globular, glomeruloid) presenting as red nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, scleroderma-like changes, either generalized or localized(legs), hyperhidrosis, clubbing, leukonychia, papilledema, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss, fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias; osteosclerotic myeloma(IgG or IgA lambda) bone lesions, progressive symmetric sensorimotor peripheral polyneuropathy, hypothyroidism, and hypogonadism; peripheral edema, thrombocytosis, cutaneous angiomas, blue dermal papules associated with Castleman’s disease(benign reactive angioendotheliomatosis), maculopapular brown-violaceous lesions, purple nodules; papilledema AD 146:615–623, 2010; JAAD 58:671–675, 2008; Blood Reviews 21:285–299, 2007; JAAD 55:149–152, 2006; JAAD 44:324–329, 2001; JAAD 40:507–535, 1999; JAAD 40:808–812, 1999; Cutis 61:329–334, 1998; Presse Med 23:646–648, 1994; Ann DV 117:283–290, 1990; JAAD 21:1061–1068, 1989; AD 124:695– 698, 1988; JAAD 12:961–964, 1985; Nippon Shinson 26:2444– 2456, 1968

Hyperpigmentation, Flagellate

503

Polyglandular autoimmune syndrome type II - Schmidt's syndrome

EXOGENOUS AGENTS

Progressive hyperpigmentation and lentigines – mutation in K17 BJD 179:1210–1211, 2018

Shiitake mushroom ingestion (raw or undercooked) Dermatol Online J April 2013

Proteus syndrome Symmetric acropigmentation of Dohi(Addison's disease, thyroid disease +/- diabetes) Cutis 59:77–80, 1997

INFECTIONS AND INFESTATIONS

Tuberous sclerosis - diffuse bronzing

Chikungunya fever

Universal dyschromatosis, small stature, and high tone deafness

Cnidarian(Portuguese man-o-war and jellyfish)stings

Werner’s syndrome(pangeria) – diffuse hyperpigmentation Medicine 45:177–221, 1966

Paederus(Rove beetles and other insects)

Whipple’s disease(Tropheryma whipplie) – Addisonian hyperpigmentation; non-palpable purpura, chronic leg edema, arthralgias; large dilated abdominal lymphatics; diarrhea, weight loss, abdominal pain, generalized hyperpigmentation, pulmonary hypertension, eye, cardiovascular, and neurologic disease JAAD 60:277–288, 2009; Clin Infect Dis 41:519–520,557–559, 2005 Winchester syndrome – thickening, hyperpigmentation and hypertrichosis, gum and lip hypertrophy, corneal opacities, musculoskeletal abnormalities Ped Derm 21:154–159, 2004 Xeroderma pigmentosum X-linked adrenoleucodystrophy – mutations in ABCD1; generalized hyperpigmentation with accentuation of elbows, knees, and gingivae and palate; accumulation of long chain fatty acids; adrenal insufficiency, myelopathy, cerebral demyelinization BJD 182:2239–2240, 2020

METABOLIC DISORDERS Systemic pruritus – excoriations

PHOTO-INDUCED DISORDERS Phytophotodermatitis

PRIMARY CUTANEOUS DISORDERS Idiopathic Ind J Derm 52:117–118, 2007

PSYCHOCUTANEOUS DISORDERS TOXINS Arsenic – diffuse pigmentation, especially of trunk; hyperpigmentation may be ashy; with depigmentation yielding rain-drop appearance Cutis 80:305–308, 2007; acute arsenic beer poisoning – garlic odor of skin; yellow-brown pigment, sore tongue, photophobia, alopecia, shedding nails BJD 165:209–210, 2011 Eosinophilia myalgia syndrome – l-tryptophan

Dermatitis artefacta Religious punishment Ind J Derm Vener Leprol 80:149–152, 2014 Sadomasochism

SYNDROMES Hypereosinophilic syndrome

Heavy metal intoxication - personal observation Thallium poisoning – generalized hyperpigmentation; anagen effluvium, gastrointestinal upset, visual impairment, Mees’ lines, perioral dermatitis, scaling of palms and soles, acneiform eruptions; treat with Prussian blue JAMADerm 152:724–726, 2016

HYPERPIGMENTATION, FLAGELLATE AUTOIMMUNE DISORDERS Allergic contact dermatitis to poison ivy Dermatomyositis Ped Derm 35:676–677, 2018 Adult onset Still’s disease JAMADerm 149:1425–1426, 2013

TRAUMA Child abuse Torture, whipping

HYPERPIGMENTATION, PARONYCHIAL AIDS Arsenic poisoning – at 3 months BJD 149:757–762, 2003 AZT S/P biopsy Bowen's disease

DRUGS Bendamustine Bleomycin Docetaxel Peplomycin

Chemotherapy Congenital nevus Ethnic pigmentation Laugier-Hunziker syndrome Malnutrition Melanoma – Hutchinson’s sign Minocycline Peutz-Jegher syndrome

504

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Polyarteritis nodosa

DEGENERATIVE DISORDERS

Pseudo-Hutchinson's sign

Reflex sympathetic dystrophy JAAD 35:843–845, 1996

Radiation therapy Regressing nevoid melanosis of childhood Retronychia (disappearing nail bed)- hyperpigmentation of proximal nail fold Ped Derm 34:717–718, 2017 Subungual hematoma Trauma

Notalgia paresthetica – hyperpigmentation of centrolateral back; association with MEN2A JAAD 74:215–228, 2016; Nervenarzt 133:188–196, 1934

DRUGS ACTH administration

HYPERPIGMENTATION, PATCHY  UTOIMMUNE DISEASES AND DISEASES OF A IMMUNE DYSFUNCTION Allergic contact dermatitis - pigmented poison ivy; pigmentation due to optical whiteners BJD 81:799–803, 1976; azo-dye coupling agents Contact Dermatitis 2:129–134, 1976; fragrances, fungicides Dermatitis herpetiformis Dermatomyositis Graft vs. host disease, chronic – poikilodermatous hyperpigmentation BJD 92:589, 1975; hyperpigmented macules with scale(leopard skin) AD 138:924–934, 2002; sclerodermoid chronic graft vs. host disease - atrophic hyperpigmented plaques BJD 156:1032–1038, 2007 Lupus erythematosus - neonatal lupus erythematosus; discoid LE H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; mutation in SLC29A3 gene(equilabrative nucleoside transporter) Ped Derm 33:602–614, 2016 IgA pemphigus – patchy hyperpigmentation BJD 171:650–656, 2014 Morphea – hyperpigmented plaque AD 147:1148–1150, 2011; linear morphea JAAD 59:385–396, 2008; morphea profunda with overlying hyperpigmentation Ped Derm 8:292–295, 1991; Borreliaassociated early onset morphea JAAD 60:248–255, 2009 Pemphigus foliaceus - personal observation Pemphigus herpetiformis - annular erythematous patches with hyperpigmentation with or without vesicles; rosette lesions Ped Derm 27:488–491, 2010; JAAD 34:40–46, 1996 Scleroderma, CREST syndrome Sjogren’s syndrome

Adriamycin Amiodarone - blue-gray pigmentation of sun-exposed areas; also yellow-brown pigmentation of the cornea JAAD 39:524–525, 1998 Amodaquine Antimalarials – blue-gray pigmentation of face, neck, forearms, lower legs AD 88:419–426, 1963; yellow and blue pigmentation of pretibial areas and hard palate JAAD 39:524–525, 1998; blue-black pigmentation of shin, face, hard palate, subungually Argyria – gray spots in topical argyria BJD 163:1124–1126, 2010 Atabrine(mepacrine) – greenish-yellow pigmentation of face, hands, feet; then diffuse Am J Med Sci 192:645–650, 1936 BCNU topical – hyperpigmentation at site of application Birth control pills Bismuth - generalized hyperpigmentation resembling argyria and/or blue-black line at the gingival margin JAAD 39:524–525, 1998 Bleomycin - flagellate hyperpigmentation JAAD 39:524–525, 1998; focal hyperpigmentation on elbows, knees, and hands AD 107:553– 555, 1973; palmar creases JAAD 40:367–398, 1999; limited to striae JAAD 28:503–505, 1993 Busulfan Capecitabine acral dysesthesia syndrome – hyperpigmentation and hyperkeratosis of the dorsal and palmar surfaces of the hands and feet of blacks Cutis 73:101–106, 2004 Carotene Chemotherapy - under adhesive bandages after chemotherapy -linear, annular and diffuse hyperpigmentation Ped Derm 8:231–235, 1991 Chemotherapy-induced eccrine neutrophilic hidradenitis JAAD 40:367–398, 1999 Chemotherapy-induced hand-foot syndrome(acral dysesthesia syndrome)(palmoplantar erythrodysesthesia syndrome) – hyperpigmentation of hands and feet in black patients - pegylated liposomal doxorubicin, capecitabine, 5-fluorouracil, cytarabine, docetaxel, sorafenib, sunitinib, axitinib, pazopanib, regorafenib, vemurafenib JAAD 71:787–794, 2014; Chloroquine

CONGENITAL LESIONS Congenital melanosis and hyperpigmentation Ped Derm 15:290– 292, 1998 Congenital smooth muscle hamartoma Hyperpigmentation of vulva, scrotum, linea nigra, and nails Pigmentary mosaicism – phylloid mosaic pigmentation Universal acquired melanosis(carbon baby)

Chlorpromazine - slate-gray hyperpigmentation in sun-exposed areas JAAD 39:524–525, 1998; longitudinal pigment bands in neonates of mothers ingesting chlorpromazine Cisplatin, carboplatin, oxaliplatin – hyperpigmentation JAAD 71:203–214, 2014 Clofazamine – initially red, then violaceous brown pigmentation in lesional areas BJD 81:794–795, 1969 Coal tar, topical Cyclophosphamide - black longitudinal or transverse bands of the nails, brown lines on the teeth, or widespread hyperpigmentation or

Hyperpigmentation, Patchy 505 limited to palms and soles JAAD 71:203–214, 2014; JAAD 39:524–525, 1998 Cyclosporine – hair darkening; hyperpigmentation of nails, palms and soles, teeth Int J Derm 38:229–230, 1999

Latanaprost(prostaglandin F2 analog) eyedrops – eyelash darkening; periorbital hyperpigmentation Arch Ophthalmol 115:1206–1208, 1997 Mechlorethamine, topical

Daunorubicin

Melphalan – brown nails

Desipramine J Clin Psychopharmacol 13:76–77, 1993

Methotrexate

Diltiazem - reticulated, perifollicular slate-gray or blue-gray, photodistributed hyperpigmentation in black patients AD 142:206– 210, 2006; Cutis 73:239–240, 2004; JAAD 46:468–469, 2004; AD 137:179–182, 2001

Minocycline – gray or blue-gray hyperpigmentation in areas of previous inflammation, on mucous membranes, and pretibial areas JAAD 44:342–347, 2001; JAAD 39:524–525, 1998; brown nails; of face JAAD 65:689–697, 2011

Doxorubicin - gray to black horizontal nail bands, hyperpigmentation of palmar creases, buccal mucosa, and face JAAD 39:524–525, 1998

Mithramycin - prominent erythema of face followed by hyperpigmentation JAAD 39:524–525, 1998

Eltrombopag – gray pigmentation of face JAMA Derm 149:1112– 1115, 2013

Palifermin – flexural hyperpigmentation, papillomatosis, and erythema; also on elbows and knees BJD 159:1200–1203, 2008

Emtricitabine - hyperpigmentation of palms and soles JAAD 63:549–561, 2010

p-amino benzoic acid – darkening of hair

Epidermal growth factor receptor inhibitors – hyperpigmentation at sites of acneiform eruption JAAD 56:317–326, 2007

Phenothiazines – blue-gray or brown photopigmentation

Fixed drug eruptions 5-fluoruracil - supravenous hyperpigmentation JAAD 39:524–525, 1998; acral pigmentation JAAD 71:203–214, 2014; 5-fluorouracil, capecitabine, tegafur – patchy hyperpigmentation JAAD 71:203–214, 2014 Gefitinib(epidermal growth factor receptor inhibitor) – hypertrichosis of the tip of the nose with underlying hyperpigmentation JAAD 77:902–910, 2017; BJD 156:1087–1088, 2007 Gold(chrysiasis) - slate-blue hyperpigmentation around the eyes and in sun-exposed areas JAAD 39:524–525, 1998; oral gold with laser therapy AD 131:1411–1414, 1995 Heavy metals Hydantoin – melasma-like Dermatologica 129:121–139, 1964 Hydroxychloroquine – pretibial brown or slate-gray pigmentation JAMADerm 149:935–940, 2013; J Cutan Pathol 35:1134–1137, 2008; Int J Dermatol 31:458–466, 1992 Hydroxyurea - nail pigmentation(brown nail discoloration) AD 135:818–820, 1999; longitudinal and/or diffuse JAAD 47:146–147, 2002; hyperpigmentation over pressure areas and back; AD 111:183–187, 1975 Imatinib mesylate(Gleevec)(multikinase inhibitor) – hair repigmentation JAAD 77:902–910, 2017; JAAD 58:545–570, 2008; NEJM 347:446, 2002; patchy hyperpigmentation of trunk and extremities J Drugs in Dermatol 10:1062–1066, 2011 Imipramine - slate-gray hyperpigmentation in sun-exposed areas JAAD 39:524–525, 1998 Interferon and ribavirin therapy BJD 149:390–394, 2003; interferon-­ alpha – treatment for chronic hepatitis C; melanonychia, facial hyperpigmentation, hyperpigmentation of tongue and buccal mucosa JAMA Derm 149:675–677, 2013

Mitomycin

Pefloxacin – blue-black pigmentation of legs AD 131:856–857, 1995 Quinine – hyperpigmentation of arms Cutis 75:114–116, 2005 Radiation recall – erythema, vesiculation, erosions, hyperpigmentation; dactinomycin and doxorubicin Mayo Clin Proc 55:711–715, 1980; edatrexate, melphalan, etoposide, vinblastine, bleomycin, fluorouracil, hydroxyurea, methotrexate Sorafenib – discoloration of face and hair BJD 161:1045–1051, 2009 Sunitinib – discoloration of face and hair BJD 161:1045–1051, 2009 Stem cell factor - subcutaneous injections of human recombinant stem cell factors Cutis 71:149–152, 2003; JAAD 33:577–583, 1995 Sulfasalazine – reversible hyperpigmentation Am J Gastroenterol 87:1654–1657, 1992 Sunitinib JAAD 77:902–910, 2017 Thiotepa - pigmentation under bandages JAAD 71:203–214, 2014; AD 125:524–527, 1989 Zidovudine JAAD 46:284–293, 2002; hyperpigmentation of palms and soles JAAD 63:549–561, 2010

EXOGENOUS AGENTS Accidental tattoos Anthralin stain from spouse - personal observation Argyria – silvery or slate-gray pigmentation of sun-exposed areas(forehead, nose, hands); may be generalized Am J Kidney Dis 37:1048–1051, 2001; BJD 104:19–26, 1981; AD 114:373–377, 1978; exogenous argyria BJD 144:191–192, 2001; argyria secondary to aerosolized solder Cutis 78:305–308, 2006

Iron – intramuscular iron injections

Chloracne - halogenated aromatic hydrocarbons – chloronaphthalenes, chlorobiphenyls, chlorobiphenyl oxides used as dielectrics in conductors and insulators, chlorophenols in insecticides, fungicides, herbicides, and wood preservatives Am J Ind Med 5:119–125, 1989

Isoniazid

Cigarette smoking(nicotine) – brown teeth, fingers

KIT and BCR-ABL inhibitors – imatinib, nilotinib, dasatinib – facial edema morbilliform eruptions, pigmentary changes, lichenoid reactions, psoriasis, pityriasis rosea, pustular eruptions, DRESS, Stevens-Johnson syndrome, urticarial, neutrophilic dermatoses, photosensitivity, pseudolymphoma, porphyria cutanea tarda, small vessel vasculitis, panniculitis, perforating folliculitis, erythroderma JAAD 72:203–218, 2015

Clothing dermatitis – pigmentation in flexures Coal tar products – pitch, asphalt, creosote – diffuse melanosis of exposed skin; evolves to atrophy, telangiectasia, lichenoid papules, follicular keratosis Collier's stripes Copper – green hair from swimming pool algicides, copper household pipes Cutis 56:37–40, 1995; green skin - copper

506 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 bracelet, copper eyeglass frames; green staining of seborrheic keratoses Cutis 77:9–41, 2006 Drug abuse NEJM 277:473–475, 1967; soot tattooing NY State J Med 68:3129–3134, 1968 Ferric sulfate, ferric chloride – red-brown tattoo Herbal potions Int J Dermatol 30:186–189, 1991 Hydroquinone – topical; exogeneous ochronosis; gray nails Jewelry cleanser – hypo- and hyperpigmentation Mercury - skin lightening creams in skin folds and eyelids JAAD 39:524–525, 1998; Int J Dermatol 30:186–189, 1991 Ochronosis, exogenous - due to benzene-containing substances, hydroquinone, mercury, phenol, quinine injections, resorcinol, antimalarials JAAD 77:591–605, 2017; Am J Clin Dermatol 2:213–217, 2001; JAAD 42:869–871, 2000; JAAD 39:527–544, 1998; Cutis 62:11–12, 1998; BJD 93:613–622, 1975; hydroquinones – speckled hyperpigmentation JAAD 29:662–664, 1993 Pine tar callus – brown macule of palm Ped Derm 36:379–380, 2019 Riehl’s melanosis – pigmented contact dermatitis due to fragrances JAAD 21:1057–1060, 1989; hyperpigmentation of face(forehead and temples), chest, neck, scalp, hands, forearms – tar compounds and cosmetics Selenium sulfide shampoo – red-brown discoloration of scalp Ped Derm 29:84–88, 2012 Stain Tattoo, accidental; tattoo pigment fanning – periorbital hyperpigmentation Cutis 68:53–55, 2001

Leishmaniasis - kala-azar; Leishmania donovani – pedal edema; primary ulcer; hyperpigmented skin of face, hands, feet abdomen; post kala-azar leishmaniasis Leprosy - pink papules with surrounding hyperpigmentation – de novo histoid leprosy Ped Derm 31:387–388, 2014 Lyme borreliosis(Borrelia burgdorferi) - acrodermatitis chronica atrophicans – red to blue nodules or plaques; tissue-paper-like wrinkling; pigmented; poikilodermatous; hands, feet, elbows, knees BJD 121:263–269, 1989: Int J Derm 18:595–601, 1979 Mansonelliasis(filariasis)(M. ozzardi) – biting midges or black flies; angioedema, chronic pruritus with hyperpigmentation, papular eruption JAAD 75:19–30, 2016 Millipede defensive secretions – mahogany pigmentation JAAD 67:347–354, 2012; Cutis 67:452, 2001; Ped Derm 8:25–27, 1991; periorbital hyperpigmentation JAAD 50:819–842, 2004 Mycetoma – hyperpigmented firm, indurated subcutaneous swellings or papules JAAD 53:931–951, 2005 Onchocerciasis – inflammatory rash with hyperpigmentation(mal morado) South Med J 80:1452–1454, 1987 Pediculosis – body louse(Vagabond's disease) Pinta – secondary – hyperpigmented macules JAAD 54:559–578, 2006; tertiary(late phase) - gray, steel, ashy, bluish spotted hyperpigmentation Portuguese man-o-war sting Pseudomonas - green staining of clothing due to pyocyanin(blue) and pyoverdin(green) pigments Cutis 86:305–308, 2010 Rubella, congenital – hyperpigmentation of forehead, cheeks, umbilical area; seborrhea, cutis marmorata JAAD 46:161–183, 2002; J Pediatr 71:311–331, 1967

INFECTIONS AND INFESTATIONS

Syphilis, secondary – diffuse hyperpigmentation of neck and shoulders with depigmented macules(mottled)

AIDS – photodermatitis, lichenoid dermatitis; generalized hyperpigmentation Int J Dermatol 38:457–463, 1999

Tinea corporis

Candida

Tinea nigra palmaris – Phaeoannelomyces(Hortae) werneckii Cutis 84:292,299–300, 2009; Ped Derm 20:315–317, 2003; AD 11:904– 905, 1975

Burrowing bug (Cydnidae) – brown macules of palms and soles Ped Derm 34:605–606, 2017; JAMADerm 151:232–233, 2015

Tinea versicolor Semin Dermatol 4:173–184, 1985; brown vulvar scaly patches Ped Derm 35:841–842, 2018

Chikungunya fever – congenital chikungunya fever; facial pigmentation(“brownie nose”)(chik sign); patchy pigmentation of hands and ankles; flagellate pigmentation of trunk and extremities; freckle-like macules, accentuation of melisma, periorbital pigmentation, confetti-­like macules; Addisonian palmar pigmentation Ped Derm 36:737–738, 2019; Ped Derm 33:209–212, 2016

Yaws

Aspergillus – green nails

Dengue fever – hyperpigmentation of nose(chik sign); transient flushing, purpuric lesions, scleral injection, morbilliform exanthema with circular islands of sparing, aphthous ulcers, lichenoid papules, flagellated pigmentation, urticarial lesions, erythema multiforme-like Ped Derm 36:737–739, 2019; Indian Dermatol Online J 8:336–342, 2017; Indian J DV Leprol 76:671–676, 2010

INFILTRATIVE DISEASES Amyloidosis, macular BJD 161:1217–1224, 2009; BJD 145:851– 852, 2001;; primary cutaneous amyloidosis - periorbital hyperpigmentation Clin Exp Derm 8:195–197, 1983; lichen and macular amyloidosis AD 133:381–386, 1997; BJD 84:199–209, 1971; primary localized cutaneous amyloid AD 123:1557–1562, 1987; macular amyloidosis as part of primary localized cutaneous amyloidosis – mutation in OSMR(oncostatin M receptor beta) AD 145:695–699, 2009; familial BJD 161:1217–1224, 2009

Erythrasma - intertriginous and perigenital; Corynebacterium minutissimum; red to brown irregularly shaped and sharply marginated scaly and slightly creased patches of groin, axillae, intergluteal, submammary flexures, toe webs coral-red fluorescence with Wood's light examination due to coproporphyrin; toe clefts are most frequent location; acanthosis nigricans and normal follicular openings of face and trunk may show coral pink fluorescence Rev Infect Dis 4:1220–1235, 1982

Erdheim-Chester disease(non Langerhans cell histiocytosis) – redbrown patches of trunk; xanthelasma-like periorbital yellow papules and plaques; CD68+, CD163+, CD1a-, Langerin(CD207)-; BRAF mutations JAAD 74:513–520, 2016

HTLV-1 - hyperpigmented facial dermatitis

Sea blue histiocytosis – facial macular brown hyperpigmentation; nodules of face, trunk, hands, and feet; eyelid infiltration; puffy face; leonine facies; nodular facial lesions JAAD 57:1031–1045, 2007; JAAD 56:302–316, 2007

Langerhans cell histiocytosis – self-healing lesions JAAD 787:1035–1044, 2018 Mastocytosis – urticaria pigmentosa Ped Derm 34:84–89, 2017

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INFLAMMATORY DISEASES Chronic erythema multiforme - personal observation Infantile systemic hyalinosis(juvenile hyaline fibromatosis) – hyperpigmentation over bony prominences with generalized thickened skin Ped Derm 23:458–464, 2006 Interstitial granulomatous dermatitis – hyperpigmented and/or poikilodermatous plaques JAAD 46:892–899, 2002; Am J Dermatopathol 21:320–323, 1999 Post-inflammatory hyperpigmentation – in blacks especially in acne vulgaris, dermatitis, lichenification, sarcoidosis, psoriasis, CTCL, lichen planus, fixed drug eruptions, lupus erythematosus JAAD 65:689–697, 2011; Cutis 32:352–360, 1983; post-inflammatory darkening of hair BJD 146:325–329, 2002; vulvar Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 189 Sarcoid Am J Med 35:67–89, 1963 Stevens-Johnson syndrome BJD 177:924–935, 2017

METABOLIC DISEASES Addison's disease – darkening of hair and nevi; perianal hyperpigmentation; linear brown hyperpigmention of nails; hyperpigmentation of genitalia, oral mucosa, linea nigra, perineum, axillae, areolae, nevi, lentigines, hair, nails, prior sites of trauma, palmar creases Ped Derm 25:215–218, 2008 Androgen excess – hyperpigmentation of areolae, axillae, external genitalia, perineum Carcinoid syndrome – pellagrous dermatitis(skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea BJD 152:71– 75, 2005; AD 77:86–90, 1958 Cirrhosis - circumscribed areas of hyperpigmentation with accentuation of freckling, areolar pigmentation, perioral and periorbital pigmentation JAAD 43:1–16, 2000 Dahl’s sign – hyperpigmentation of medial thighs due to elbow pressure in chronic obstructive airway disease(Thinker’s sign) NEJM 371:357, 2014 Diabetes mellitus – diabetic dermopathy(annular atrophic patches of legs) JAAD 58:447–451, 2008; Am J Med Sci 251:570–575, 1966; AD 93:282–286, 1966; AD 92:625–634, 1965;Acta Med Scand 176(Suppl)1–75, 1964; pigmented hypertrichotic indurated plaques of thighs Ped Derm 24:101–107, 2007 Fanconi’s anemia – autosomal recessive; dyschromatosis; oral leukoplakia, oral and vulvar squamous cell carcinoma, short stature, absent radii, bone marrow failure, endocrine abnormalities, café au lait macules, guttate hypopigmentation, intertriginous hyperpigmentation, broad nose, epicanthal folds, micrognathia JAAD 54:1056– 1059, 2006 Folic acid deficiency – hyperpigmentation of the flexures; finger and palmar creases, knuckles; spotty pigmentation of palms and soles JAAD 12:914–917, 1985 Gaucher's disease – melasma-like pigmentation of face, neck, hands; symmetric pigmentation of lower legs with sharp lower margin and irregular upper margin; hyperpigmented wedge-shaped thickening of bulbar conjunctiva Hemochromatosis – black hyperpigmented speckling of edematous legs; hyperpigmentation of areolae, flexures, and mucous membranes AD 143:1441–1446, 2007; Medicine 34:381–430, 1955 Hemolytic anemia – hyperpigmentation and hemosiderosis of lower legs

Hyperthyroidism – patchy hyperpigmentation or diffuse Addisonian hyperpigmentation sparing oral mucosa JAAD 26:885–902, 1992; hyperpigmentation of eyelids(Jellinek’s sign); melasmic hyperpigmentation BJD 76:126–139, 1964 Idiopathic thrombocytopenic purpura with iron overload - legs Kwashiorkor - facial pigmentation; Vitamin B complex deficiency, folic acid deficiency, iron deficiency, tryptophan Cutis 67:321–327, 2001 Liver disease, chronic – diffuse muddy gray hyperpigmentation with accentuation in perioral, periorbital, and areolar regions; hyperbilirubinemia – green palms AD 146;209–210, 2010 Malabsorption Malnutrition – brown bands of nails Necrobiosis lipoidica diabeticorum Int J Derm 33:605–617, 1994; JAAD 18:530–537, 1988 Nutritional deficiencies, including vitamin B12 Cutis 61:229–232, 1998 Ochronosis – generalized hyperpigmentation with accentuation over cheeks, forehead, axillae, and genitalia, buccal mucosa, nails; chromhidrosis; brown eyelids Pancreatic panniculitis – heal with post-inflammatory hyperpigmented JAAD 34:362–364, 1996; Arthritis Rheum 22:547–553, 1979; Am J Gastroenterol 83:177–179, 1988 Pellagra – after acute photosensitivity subsides, dusky red-brown hyperpigmentation remains; hyperkeratotic and hyperpigmented elbows, knees, ankles, skin over spinous processes BJD 164:1188– 1200, 2011 Pernicious anemia(Vitamin B12 deficiency) – diffuse or mottled of face, hands, and feet J Dermatol 28:282–285, 2001;– hyperpigmentation of the flexures; finger and palmar creases, knuckles; pigmented bands of nails AD 122:896–899, 1986 Phrynoderma – follicular hyperkeratotic papules, xerosis, patchy hyperpigmentation Ped Derm 28:346–349, 2006 Porphyrias - hereditary coproporphyia, congenital erythropoietic porphyria Semin Liver Dis 2:154–63, 1982; porphyria cutanea tarda – diffuse hyperpigmentation like hemochromatosis; melismalike hyperpigmentation and hyperpigmentation limited to the legs AD 125:297–299, 1989; darkening of hair BJD 146:325–329, 2002; variegate porphyria Wien Klin Wochenschr 50:830–831, 1937; BMJ ii:89, 1955; hepatoerythropoietic porphyria AD 116:307–313, 1980; Pregnancy – hyperpigmentation including melasma, linea nigra, neck, nipples, anogenital skin porphyria cutanea tarda following chemotherapy for acute lymphoblastic leukemia in 8 year old child J Drugs Dermatol 13:489–491, 2014 Scurvy Sickle cell anemia – hemosiderin deposition of legs Thalassemia – leg ulcers with shiny pigmented skin Vitamin B6 deficiency – scrotal hyperpigmentation Ped Derm 16:95–102, 1999

NEOPLASTIC DISEASES Acquired bilateral nevus of Ota-like macules(Hori’s nevus) JAAD 65:689–697, 2011 Actinic keratosis – spreading pigmented actinic keratosis JAAD 63:499–506, 2010 Anal intraepithelial neoplasia – perianal hyperpigmented patches, white and/or red plaques JAAD 52:603–608, 2005 Angiosarcoma in radiation site – late skin thickening and induration, edema, and dyspigmentation JAAD 49:532–538, 2003

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Becker's nevus NEJM 372:1249, 2015; Arch Dermatol Syphilol 60:155–160, 1949 Benign vulvar melanosis Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 187 Blue nevus, cellular - periorbital pigmentation Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.89 Bowen's disease - linear longitudinal melanonychia JAAD 39:490– 493, 1998; AD 129:1043–1048, 1993; vulvar Bowen’s disease Ann DV 109:811–812, 1982; Cancer 14:318–329, 1961 Breast cancer - pigmented breast carcinoma AD 125:536–539, 1989 Castleman’s disease – widespread oval hyperpigmented patches in pityriasis rosea distribution JAAD 65:430–432, 2011 Congenital multiple clustered dermatofibroma – hyperpigmented patch with papules and some depressed areas Ped Derm 31:105– 106, 2014; J Cutan Pathol 37:e42–45, 2010; BJD 142:1040–1043, 2000 Dermal dendrocyte hamartoma – medallion-like; annular brown or red congenital lesion of central chest with slightly atrophic wrinkled surface JAAD 51:359–363, 2004 Dermal melanocytic hamartoma - blue or gray Clin Derm 37:507– 515, 2019 Dermal melanocytosis – blue or gray Clin Derm 37:507–515, 2019 Eccrine nevus – macular or depressed brown patch JAAD 51:301– 304, 2004 Ephelides Epidermolysis bullosa nevi(recessive dystrophic EB) – irregular hyperpigmented patches JAMA Derm 149:1148–1149, 2013; AD 143:1164–1167, 2007 Eruptive vellus hair cysts - blue-gray discoloration of face masquerading as nevus of Ota BJD 157:188–189, 2007; AD 113:500–503, 1977 Fat storing hamartoma of dermal dendrocytes - patch of lumbosacral hyperpigmentation AD 126:794–796, 1990 Kaposi's sarcoma in AIDS - flat lesions JAAD 38:143–175, 1998; JAAD 22:1237–1250, 1990; S/P treatment AD 147:779—781, 2011 Large cell acanthoma - macular hyperpigmentation Cutis 47:97– 100, 1991 Large plaque parapsoriasis Lentigo maligna JAAD 72:801–808, 2015; AD 147:1191–1195, 2011 Leukemia cutis mimicking stasis dermatitis Cutis 35:47–8, 1985 Lymphoma - cutaneous T-cell lymphoma Dermatology 192:360– 363, 1996; evolving from pigmented purpuric eruptions; CD8+ CTCL – focal hyperpigmentation AD 138:199–203, 2002; CD8+ predominant CTCL - hyperpigmented patches JAAD 67:69–75, 2012; lymphomatoid granulomatosis(angiocentric lymphoma) - red, brown, or violaceous plaques with epidermal atrophy and purpura JAAD 20:571–578, 1989; AD 124:571–576, 1988; Hodgkin’s disease – Addisonian pigmentation of nipples, axillae, groin; widespread or patchy; intravascular B-cell lymphoma – indurated hyperpigmented sclerodermoid plaques of thighs AD 148:247–252, 2012; juvenile cutaneous T-cell lymphoma – hypo- and hyperpigmented patches JAAD 71:1117–1126, 2014; peripheral T-cell lymphoma – red-brown macule BJD 173:134–145, 2015; intertriginous poikilodermatous CTCL JAMADerm 155:958–959, 2019 Melanoacanthoma Melanocytic agminated nevus of the sole BJD 146:154, 2002

Melanocytic nevi – melanocytic nevi of genitalia in the presence of lichen sclerosus JAAD 50:690–694, 2004; congenital melanocytic nevus; epidermolysis bullosa nevi BJD 153:97–102, 2005; combined nevus Melanoma – in situ melanoma JAAD 73:181–190, 2015; lentigo maligna; lentigo maligna – localized hair repigmentation JAMADerm 152:81–82, 2015; acral lentiginous melanoma(atypical melanosis of the foot) BJD 172:1436–1438, 2015; BJD 160:591–599, 2009; melanoma of the vulva BJD 155:215–217, 2006; JAAD 50:293–298, 2004; Int J Gynecol Cancer 11:359–364, 2001; Cancer 86:1273– 1284, 1999; acral melanoma – hyperpigmented patches of soles JAMA Derm 149:1281–1288, 2013; metastatic melanoma – desmoplastic melanoma – shock of hyperpigmented hair BJD 169:1371– 1372, 2013; periorbital gray pigmentation Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.83; eruptive pigmentation around nevi and seborrheic keratoses in stage III melanoma – hyperpigmented halo or “nottus” phenomenon BJD 168:1140–1141, 2013; vulvar melanoma BJD 170:1219–1225, 2014; primary dermal melanoma – pedunculated pink papule, dark macule, blue pigmented nevus, dome-shaped hemorrhagic papule, changing pigmented nevus JAAD 71:1083– 1091, 2014 Melanosis of the areola and nipple JAAD 59:S33–34, 2008; AD 126:542–543, 1990 Metastases - sclerodermoid hyperpigmented plaques of breasts – metastatic renal cell carcinoma AD 147:1215–1220, 2011; metastatic breast carcinoma brown nails Mongolian spot Mucinous eccrine nevus – hyperpigmented plaque Ped Derm 25:573–574, 2008 Myeloma – mimicking acral lentiginous melanoma JAAD 62:1076– 1078, 2010 Nevus of Ito(nevus fuscoceruleus acromio-deltoideus) - blue or gray Clin Derm 37:507–515, 2019; Tohou J Exp Med 60:10–20, 1954 Nevus of Ota(nevus fuscoceruleus ophthalmomaxillaris) – blue or gray Clin in Derm 37:507–515, 2019; BJD 67:317–319, 1955; tardive nevus of Ota - personal observation Nevus spilus(speckled and lentiginous nevus) Ped Derm 13:250– 252, 1996; AD 114:895–896, 1978 Paget’s disease – vulvar pigmented extramammary Paget’s disease; hyperpigmented plaque BJD 142:1190–1194, 2000; pigmented Paget’s disease of the nipple in men; mimics melanoma of the breast JAAD 55:S62–63, 2006; Melanoma Research 14:S13–15, 2004; Dermatology 202:134–137, 2001; Ann DV 128:649–652, 2001; Hautarzt 43:28–31, 1992; Histopathology 19:470–472, 1991; JAAD 23:338–341, 1990 Pagetoid dyskeratosis JAAD 50:483–484, 2004; brown macules on thumb tip AD 148:247–252, 2012 Plexiform neurofibroma – patchy hyperpigmentation of overlying skin Textbook of Neonatal Dermatology, p.402, 2001 Post-transplant lymphoproliferative disorder – violaceous macules, facial nodules Ped Derm 36:681–685, 2019 Seborrheic keratosis Smooth muscle hamartoma – hyperpigmentation and hypertrichosis JAAD 46:477–490, 2002; Arch Dermatol Syphil 7:479–481, 1923 Tumors of the follicular infundibulum J Cutan Pathol 40:532–537, 2013; Dermatol Surg 30:1246–1248, 2004; JAAD 33:979–984, 1995 Waldenstrom's macroglobulinemia – red-brown or violaceous macules – neoplastic B-cell infiltrates AD 120:778–781, 1984

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PARANEOPLASTIC DISORDERS Acanthosis nigricans Glucagonoma syndrome – necrolytic migratory erythema; resolution leaves hyperpigmentation JAAD 54:745–762, 2006; JAAD 12:1032– 1039, 1985

PHOTODERMATOSIS Actinic lichen planus - hyperpigmented patches of the face AD 135:1543–1548, 1999; tropical lichen planus(lichenoid melanodermatitis) BJD 101:651–658, 1979; mimicking melasma JAAD 18:275–278, 1988 Acquired bilateral nevus of Ota-like macules(Hori nevus) – bluebrown or slate-gray macules, speckled or confluent BJD 166:692– 694, 2012; JAAD 61:88–93, 2009; BJD 117:545–553, 1987; JAAD 10:961–964, 1984 Berloque dermatitis AD 90:572–576, 1964 Ephelides(freckles) – autosomal dominant Melasma – upper lip, cheeks, forehead, chin BJD 172:1535–1540, 2015; J Drugs in Dermatol 10:517–523, 2011; JAAD 15:894–899, 1986; JAAD 4:698–710, 1981 Phototherapy of neonatal jaundice – darkening of treated areas J Pediatr 82:1042–1043, 1973 Phytophotodermatitis, - lemon, lime, celery, parsnip, figs, carrots, dill, parsley, meadowgrass, giant hogweed, wheat, clover, cocklebar, buttercup, shepherd’s purse, pigweed JAAD 67:1093–1110, 2012; Poikiloderma of Civatte Ann Dermatol Syphilol 9:381–420, 1938 Riehl’s melanosis - brown or gray Clin in Derm 37:507–515, 2019 Sunburns

PRIMARY CUTANEOUS DISEASES

Cutis tricolor – hyper- and hypopigmented lesions with a background of normal skin Eur J Pediatr 159:745–749, 2000 Dentinogenesis imperfecta – brown stained hypoplastic teeth Epidermolysis bullosa simplex herpetiformis(Dowling-Meara) with mottled pigmentation Ped Derm 13:306–309, 1996 Epidermolysis bullosa simplex with mottled pigmentation of neck, upper trunk, arms and leg with or without keratoderma(punctate palmoplantar keratoses); cutaneous atrophy, nail dystrophy BJD 150:609–611, 2004; JAAD 15:1289–1291, 1986; Clin Genet 15:228–238, 1979 Epidermolysis bullosa - alpha6-beta4 epidermolysis bullosa – mild blistering and crusting, severe skin fragility, patchy hyperpigmentation of elbows; onychogryphosis; yellow-brown discoloration of teeth with enamel defects BJD 169:115–124, 2013 Epidermolysis bullosa - ITGB4-associated non-Herlitz junctional epidermolysis bullosa – onychogryphosis, prurigo papules of dorsal hands, alopecia of pubic hair, bullae, erosions, crusts, and hyperpigmentation BJD 168:432–434, 2013 Erythema annulare centrifugum – hyperpigmentation, rarely Bull Soc Fr Dermatol Syphiligr 71:450–452, 1964 Erythema dyschromicum perstans(ashy dermatosis) - blue-gray patches with red raised margins; coalesce over face, trunk, and extremities; hypo- and hypermelanotic macules resembling late pinta Cutis 68:25–28, 2001; AD 124:1258–1260, 1988; Int J Derm 24:630–633, 1985 Erythema elevatum diutinum - healed giant annuli BJD 143:415– 420, 2000 Erythromelanosis follicularis of face and neck(faciei et colli) – redbrown pigmentation with telangiectasias, follicular papules involving preauricular and maxillary regions Ped Derm 23:31–34, 2006; JAAD 32:863–866, 1995; Hautarzt 9:391–393, 1960 Erythrose peribuccale pigmentaire of Brocq – diffuse brown pigmentation around mouth with narrow perioral sparing; central face, forehead, angles of jaw, temples

Acanthosis nigricans JAAD 65:689–697, 2011; Am J Public Health 84:1839–1842, 1994; of face JAAD 56:901–916, 2007; acral acanthosis nigricans(acral acanthotic anomaly) – hyperpigmentation of elbows, knees, and knuckles JAAD 5:345–346, 1981; familial acanthosis nigricans with hyperpigmented plaques – K6507FGFR3 mutation AD 143:1153–1156, 2007

Facial hyperpigmentation in Africans – bleaching creams, mercury, photosensitizing herbs, fixed drug eruptions, melasma Int J Derm 30:186–191, 1991

Acquired dermal melanocytosis – blue-black JAAD 45:609–613, 2001

Hematohidrosis

Acrogeria – mottled hyperpigmentation of acral skin BJD 142:178– 180, 2000

Hypermelanosis in a phylloid pattern – also Blaschko hyperpigmentation of face; associated with spina bifida; musculoskeletal abnormalities JAAD 60:697–700, 2009

Acromelanosis - black patients JAAD 2:128–131, 1980; Cutis 5:1119–1120, 1969

Familial progressive hyperpigmentation Ped Derm 34:84–89, 2017 Follicularis faciei et colli Human chimera with pigment anomalies BJD 103:489–498, 1980

Acromelanosis progressiva AD 86:412–418, 1962

Hyperpigmented macules of palms and soles in blacks Int J Dermatol 18:222–225, 1979

Atrophoderma of Moulin – acquired atrophic pigmented band-like lesions following Blaschko’s lines JAAD 49:492–498, 2003;

Idiopathic eruptive macular hyperpigmentation – hyperpigmented patches JAAD 67:69–75, 2012

Ann DV 119:729–736, 1992

Keratosis lichenoides chronica - in children; patchy hyperpigmentation of face JAAD 56:S1–5, 2007; Arch Dermatol Syph(Berlin) 31:1–32, 1895

Atrophoderma of Pasini and Pierini JAAD 77:930–937, 2017; Dermatol 190:203–206, 1995; JAAD 30:441–446, 1994; Int J Derm 10:643–645, 1984 Axillary apocrine chromhidrosis AD 124:494–496, 1988 Brachioradial pruritus – erosions and hyperpigmentation Cutis 102:185–186,189–190, 2018; JAAD 74:215–228, 2016; AD 98:481–485, 1968 Chromhidrosis – black, violet, blue, brown, yellow, green, rarely red Confluent and reticulated papillomatosis of Gougerot and Carteaud Am J Clin Dermatol 7:305–313, 2006

Lichen aureus - personal observation Lichen planus - lichen planus pigmentosus JAAD 21:815, 1989; Dermatologica 149:43–50, 1974; lichen planus pigmentosus and frontal fibrosing alopecia - facial hyperpigmentation BJD 175:1387– 1390, 2016; lichen planus pigmentosus inversus – linear gray-brown macules of of intertriginous areas in folds of chest, abdomen, and groin AD 147:1097–1102, 2011; lichen planus pigmentosus – hyperpigmentation of face and neck BJD 168:439–442, 2013; lichen

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planus tropicus; photopigmentation in lichen planus actinicus BJD 163:662–663, 2010 Lichen planus pigmentosus – facial, truncal, Blaschko-esque pigmentation JAAD 77:591–605, 2017; SkinMed 11:96–103, 2013; gray Clin in Derm 37:507–515, 2019 Lichen simplex chronicus – in blacks; vulvar lichen simplex chronicus JAAD 23:982–984, 1990 Linear and whorled nevoid hypermelanosis JAAD 19:1037–1044, 1988; Ped Derm 10:156–158, 1993   vs. Chimerism Conradi-Hunermann syndrome(streaked hyperpigmentation and hyperkeratosis) JAAD 21:248–256, 1989   Dyschromatosis universalis   Early epidermal nevus   Familial progressive hyperpigmentation   Hypomelanosis of Ito   Incontinentia pigmenti Lichen sclerosus et atrophicus Melasma JAAD 65:689–697, 2011 Mosaic pigmentation - personal observation Necrolytic acral erythema - acral velvety hyperpigmented and hyperkeratotic plaques of distal dorsal feet; red palms with desquamation, erythroderma with flaccid bullae, edema and desquamation of face, onychodystrophy and onycho madesis; hepatitis C Cutis 84:301–304, 2009 Notalgia paresthetica BJD 165:1359–1361, 2011; JAAD 18:25–30, 1988; Cutis 23:471–473, 1973 Occupational melanosis Periorbital hyperpigmentation AD 100:169–174, 1969  Familial   Lichen planus   Mercurial preparations – blue or gray-brown  Post-traumatic   Psoralens in cosmetics  Silver preparations – blue or gray-brown Phylloid hypermelanosis – cicatricial alopecia, onychodystrophy, deafness, malformed ear, mental retardation, umbilicated nipples JAAD 19:1037–1044, 1988; Rev Neurol(Paris)95:48–54, 1956 Pigmentary lines of demarcation  Type A - Futcher's lines, Voigt's lines - dorsoventral line on the upper anterior aspects of the arms   Type B - posteromedial aspect of legs  Type C - pair of vertical hypopigmented lines over the presternal region  Type D - posteromedian line, hyperpigmented over midback in Asians   Type E - periareolar hypopigmentation in black children Pigmentary mosaicism – phylloid hyperpigmentation BJD 149414– 416, 2003 Pityriasis lichenoides chronica JAAD 56:205–210, 2007 Poikiloderma vasculare atrophicans - personal observation Progressive cribriform and zosteriform hyperpigmentation AD 114:98–99, 1978 Prurigo pigmentosa Cutis 63:99–102, 1999; BJD 120:705–708, 1989; AD 125:1551–1554, 1989; JAAD 12:165–169, 1985 Pseudo-ochronosis Riehl’s melanosis – rapid onset of gray-brown reticulated hyperpigmentation of the face JAAD 77:591–605, 2017; J Drugs Dermatol 13:356–358, 2014

Scleredema of Buschke(pseudoscleroderma) – with IgG-lambda paraproteinemia; hyperpigmentation of involved skin AD 123:629– 632, 1987 Subcorneal pustular dermatosis of Sneddon-Wilkinson – pustules which expand to annular and serpiginous lesions with scaly edge; heal with hyperpigmentation J Dermatol 27:669–672, 2000; Cutis 61:203–208, 1998; JAAD 19:854–858, 1988; BJD 68:385–394, 1956 Symmetrical acrokeratoderma(?acanthosis nigricans) – hyperpigmented hyperkeratotic flexural regions and dorsal hands JAAD 70:533–538, 2014 Terra firme(Diogenes syndrome) – hyperpigmented hyperkeratotic plaques of neck of teenagers and pre-teens Ped Derm 29:297–300, 2012; self-neglect Lancet i:366–368, 1975 Transient neonatal pustular melanosis Vitiligo, pigmented Vulvar melanosis JAAD 71:1241–1249, 2014   Differential diagnosis:   Bannayan-Riley-Ruvalcaba syndrome   Carney complex   Dowling-Degos syndrome   LEOPARD syndrome   Peutz-Jegher’s syndrome

PSYCHOCUTANEOUS DISORDERS Factitial chromhidrosis; factitial pigmentation(dermatitis simulata) J R Coll Physicians Lond 17:199–205, 1983; focal hyper- and hypopigmentation due to factitial inhaler(salbutamol) exposure Ped Derm 24:499–500, 2007; patchy hyperpigmentation - Ped Derm 32:604–608, 2015

SYNDROMES Acromelanosis progressiva - autosomal recessive; sharply demarcated pigmented patches of the dorsal fingers of infants, spread to head, neck, perineum, and extremities JAAD 10:1–16, 1984 Albright's syndrome Anhidrotic ectodermal dysplasia – hyperpigmentation around mouth and eyes; mutation in ectodysplasin A1 isoform(EDA-1) receptor(ADAR) BJD 157:207–209, 2007 Ankyloblepharon-ectrodactyly-cleft lip/palate(AEC) syndrome – hyper- and hypopigmentation AD 141:1591–1594, 2005 Anonychia with bizarre flexural pigmentation – autosomal dominant, absent nails, dry peeling palmoplantar skin, coarse and sparse frontal hair; mottled hyper- and hypopigmentation of the axillae, groin, and natal cleft BJD 92:469–474, 1975 Ataxia telangiectasia Bannayan-Riley-Ruvulcaba syndrome - pigmented macules(CALMs) on penis and vulva AD 132:1214–1218, 1996 Bazex syndrome Bazex-Dupre-Christol syndrome – congenital hypotrichosis, follicular atrophoderma, basal cell nevi and basal cell carcinomas, facial milia, hypohidrosis, pinched nose with hypoplastic alae, atopy with comedones, keratosis pilaris, joint hypermobility, scrotal tongue, hyperpigmentation of the forehead JAAD 74:437–451, 2016; BJD 153:682–684, 2005; Dermatol Surg 26:152–154, 2000; Hautarzt 44:385–391, 1993 Beare-Stevenson syndrome - cutis gyrata(furrowed skin), corrugated forehead, acanthosis nigricans, macular hyperpigmentation of

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antecubital and popliteal fossae, hypertelorism, swollen lips, swollen fingers, prominent eyes, ear anomalies, and umbilical herniation Ped Derm 20:358–360, 2003

Familial sea-blue histiocytosis – autosomal recessive; patchy gray pigmentation of face, upper chest, shoulders; eyelid edema, facial nodules Dermatologica 174:39–44, 1987

Becker’s nevus syndrome – breast hypoplasia Am J Med Genet 68:357–361, 1997; supernumerary nipples BJD 136:471–472, 1997; Clin Exp Dermatol 22:240–241, 1997; hypoplastic nipples Am J Med Genet 77:76–77, 1998; familial Becker's nevus Dermatologica 176:275–276, 1988

Familial transverse nasal hyperpigmentation J Hered 65:157–159, 1974

Becker’s syndrome – discrete or confluent brown macules of neck, forearms Arch Dermatol Syphilol 40:987–998, 1939 Bloom's syndrome – irregular hyperpigmentation of trunk and extremities Syndromes of the Head and Neck, p.298, 1990 Cantu’s syndrome – autosomal dominant; hyperpigmented macules of face, forearms, and feet, hyperkeratotic palms and soles Clin Genet 14:165–168, 1978 Carney syndrome CHILD syndrome without congenital hemidysplasia – extensive lentigo simplex, linear epidermolytic nevus, and epidermolytic nevus comedonicus; mutation in KRT10 BJD 173:293–296, 2015 Congenital reticular ichthyosiform erythroderma(ichthyosis variegata) BJD 139:893–896, 1998 Cowden’s syndrome – acromelanosis Cronkhite-Canada syndrome - lentigo-like macules of face, extremities, and diffuse pigmentation of palms; hyper- and hypopigmented macules of dorsal fingers; gastrointestinal polyposis, malabsorption, alopecia, dystrophic nails JAAD 63:172–174, 2010; AD 135:212, 1999; Cutis 61:229–232, 1998 Crouzon's syndrome - hyperpigmentation and hyperelasticity Digitocutaneous dysplasia – X-linked dominant; digital fibromas, atrophic plaques with appearance of hyperpigmentation, metacarpal and metatarsal disorganization with resultant brachydactyly and clinodactyly, dysmorphic features including frontal bossing, broad nasal root, telecanthus and epicanthal folds, conical teeth, dental fissures, hypodontia, accessory gingival frenula, enamel hypoplasia JAAD 56:S6–9, 2007 Dowling-Degos disease – vulvar brown macules AD 144:417–418, 2008; Dyschromatosis symmetrica hereditaria – freckles of face and hands JAAD 63:529–530, 2010 Dyskeratosis congenita Ehlers-Danlos syndrome type VIII – gingivitis, atrophic translucent hyperpigmented skin of shins Ped Derm 24:189–191, 2007; Clin Pediatr 34:552–555, 1995 Familial hyper- and hypopigmentation with age-related pattern change(cutis tricolor) – multiple hypopigmented macules and patches with hyperpigmented patches; as patient ages see smaller hyper- and hypopigmented macules and hyperpigmented patches; mutation in KITLG(kit ligand) BJD 175:1369–1371, 2016; Am J Med Genet A 15:132A:215–218, 2005; Eur J Dermatol 13:343–345, 2003 Familial mandibuloacral dysplasia - mottled hyperpigmentation of hands, feet, trunk, and extremities Familial melanopathy with gigantic melanocytes Familial multiple cafe au lait macules AD 130:1425–1426, 1994 Familial periorbital hyperpigmentation AD 100:169–174, 1969; Cutis 5:579, 1969 Familial progressive hyperpigmentation - macular hyperpigmentation of skin, oral, and ocular mucosa, whorls, streaks, and retiform patches Curr Prob in Derm VII:143–198, 1995

Fanconi’s anemia – autosomal recessive; endocrine abnormalities with hypothyroidism, decreased growth hormone, diabetes mellitus, café au lait macules, diffuse hyperpigmented macules, guttate hypopigmented macules, intertriginous hyperpigmentation, skeletal anomalies(thumb hypoplasia, absent thumbs, radii, carpal bones), oral/genital erythroplasia with development of squamous cell carcinoma, hepatic tumors, microphthalmia, ectopic or horseshoe kidney, broad nose, epicanthal folds, micrognathia, bone marrow failure, acute myelogenous leukemia, solid organ malignancies JAAD 54:1056–1059, 2006 Generalized nevoid hyperpigmentation J Cutan Dis 37:687–701, 1919 Goltz’s syndrome(focal dermal hypoplasia) – patchy hyperpigmentation Ped Derm 20:249–253, 2003; male mosaic Goltz’s syndrome; blaschko-­linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011 H syndrome(low height, heart, hallus valgus, hormonal, hypogonadism, hematologic) – sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; starts on feet and legs and progresses upward; hypertrichosis, short stature, facial telangiectasia, ichthyosiform changes, gynecomastia, varicose veins, skeletal deformities(camptodactyly of 5th fingers), scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, micropenis, azospermia, sensorineural hearing loss, dilated scleral vessels, exophthalmos, cardiac anomalies, hepatosplenomegaly, mental retardation; mutation in nucleoside transporter Hent3 JAAD 70:80–88, 2014; BJD 162:1132–1134, 2010; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008 Hermansky-Pudlak syndrome – freckling in sun-exposed skin JAAD 19:217–255, 1988 Hutchinson-Gilford syndrome – patchy hyperpigmentation JAMADerm 150:197–198, 2014 Hypereosinophilic syndrome – brown macules Ped Derm 35:860, 2018 Incontinentia pigmenti - brown or gray Clin Derm 37:507–515, 2019; Am J Dis Child 139:711–712, 1985; AD 112:535–542, 1976 Juvenile hyaline fibromatosis – hyperpigmentation of metacarpophalangeal joints and malleoli Ped Derm 21:154–159, 2004 Kindler’s syndrome – patchy hyperpigmentation and hypopigmentation; bullae, crusts, erosions, cigarette paper atrophy JAMA 306:767–768, 2011 Laugier-Hunziger syndrome Localized hereditary pruritus Mandibuloacral dysplasia – autosomal recessive; progeroid facies; facial asymmetry, micrognathia, small nose, prominent eyes, large open fontanelles; congenital brown pigmentation of ankles progresses to mottled pigmentation; hypoplastic clavicles; contractures of lower extremities; failure to thrive; progressive glomerulopathy; subcutaneous calcified nodules; mutation in ZMPSTE24(lamin) JAMADerm 151:561–562, 2015 McCune-Albright syndrome(polyostotic fibrous dysplasia) – giant café au lait macules Ped Derm 8:35–39, 1991; Dermatol Clin 5:193–203, 1987

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MELAS syndrome - mitochondrial encephalomyopathy with lactic acidosis - reticulated hyperpigmentation JAAD 41:469–473, 1999 Mitochondrial DNA syndrome – mottled hyperpigmentation Pediatrics 103:428–433, 1999; JAAD 39:819–823, 1998

58:671–675, 2008; JAAD 55:149–152, 2006; JAAD 44:324–329, 2001; JAAD 40:507–535, 1999; JAAD 40:808–812, 1999; JAAD 21:1061–1068, 1989;

Mottled pigmentation of neck and elbows Z Haut-u Geschl Krankh 32:33–44, 1962

AD 124:695–698, 1988; Cutis 61:329–334, 1998; JAAD 21:1061– 1068, 1989; JAAD 12:961–964, 1985; Nippon Shinson 26:2444– 2456, 1968

Moynahan’s syndrome – lentigines, congenital mitral stenosis, dwarfism, mental retardation, genital hypoplasia

Prader-Willi syndrome – hypopigmentation, mental retardation Am J Med Genet 40:454, 1991

Multiple mucosal neuroma syndrome(MEN IIB) - perioral or periocular hyperpigmentation, lentigines, or freckles

Proteus syndrome – port wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation Am J Med Genet 27:87–97, 1987; Pediatrics 76:984–989, 1985; Eur J Pediatr 140:5–12, 1983

NAME/LAMB syndromes; MEN IIA - hyperkeratosis and hyperpigmentation in localized pruritic patch between the scapulae JAAD 42:939–969, 2000 Neurofibromatosis, including enlarging hyperpigmented plaque; plaque type neurofibroma AD 140:751–756, 2004 Nevoid basal cell carcinoma syndrome with type 2 mosaicism – Blaschko-esque atrophy, Blaschko-esque pits of palms; linear papules of foot; white papules and plaques; segmental hyper- and hypopigmented patches BJD 169:1342–1345, 2013 Niemann-Pick disease – autosomal recessive; sphingomyelinase deficiency; indurated hyperpigmented patches of cheeks Am J Dis Child 136:650–651, 1982 Noonan's syndrome - early onset stasis dermatitis Pallister-Killian syndrome – mental retardation, coarse facies with hypertelorism and prominent forehead, sparse temporal hair and high frontal hairline, hypo- and hyperpigmentation, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i(12p)(tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005 Parry-Romberg syndrome Ped Derm 21:48–50, 2004; JAAD 22:531–533, 1990 Phakomatosis pigmentokeratotica - coexistence of an organoid nevus(nevus sebaceous/epidermal nevus) and a contralateral segmental lentiginous or papular speckled lentiginous nevus JAAD 63:1–22, 2010; Ped Derm 25:76–80, 2008; Dermatology 194: 77–79, 1997; speckled lentigines of soles JAAD 55:S16–20, 2006 Phakomatosis pigmentovascularis – port wine stain, oculocutaneous(dermal and scleral) melanosis, CNS manifestations; type I – PWS and linear epidermal nevus; type II – PWS and dermal melanocytosis(Mongolian spot); type III – PWS and nevus spilus; type IV – PWS, dermal melanocytosis, and nevus spilus J Dermatol 26:834–836, 1999; AD 121:651–653, 1985

Punctate acrokeratoderma with pigmentary disorder BJD 128:693– 695, 1993 Rosai-Dorfman syndrome – hyperpigmented plaques BJD 145:323–326, 2001 Rothmund-Thomson syndrome AD 75:236–244, 1957 Russel-Silver syndrome Speckled lentiginous nevus syndrome – speckled lentiginous nevus with ipsilateral sensory and motor neuropathy, hyperhidrosis, spinal muscle atrophy with fasciculations, dysesthesias, muscle weakness Eur J Dermatol 12:133–135, 2002; ipsilateral shortening of limb and vertebral malformations Acta DV(Stockh)74:327–334, 1994 Tay syndrome Tricho-odonto onycho-ectodermal dysplasia(linear dermal hypoplasia) - hypotrichosis, hypodontia, focal linear dermal hypoplasia of the tip of the nose, irregular hyperpigmentation of the back, bilateral amastia and athelia, nerve hearing loss AD 122: 1047–1053, 1986 Trichothiodystrophy syndromes - BIDS, IBIDS, PIBIDS – hyperpigmented eyelids, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997 Trisomy 14 mosaicism syndrome – patchy reticulated hyperpigmentation resembling that of incontinentia pigmenti Syndromes of the Head and Neck, p.89, 1990

Piebaldism – autosomal dominant; white forelock, white patches on upper chest, abdomen, extremities with islands of hyperpigmentation within JAAD 44:288–292, 2001; mutations and deletions of c-kit(steel factor receptor) Am J Hum Genet 56:58–66, 1995

Unusual facies, vitiligo, canities, and progressive spastic paraplegia – hyperpigmentation of exposed areas Am J Med Genet 9:351–357, 1981

POEMS syndrome(Crowe-Fukasi syndrome, Takatsuki syndrome) (PEP syndrome – plasma cell dyscrasia, endocrinopathy, polyneuropathy) – plethora, angiomas(cherry, globular, glomeruloid) presenting as red nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, scleroderma-like changes, either generalized or localized(legs), hyperhidrosis, clubbing, leukonychia, papilledema, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss, fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias; osteosclerotic myeloma(IgG or IgA lambda) bone lesions, progressive symmetric sensorimotor peripheral polyneuropathy, hypothyroidism, and hypogonadism; peripheral edema, thrombocytosis, cutaneous angiomas, blue dermal papules associated with Castleman’s disease(benign reactive angioendotheliomatosis), maculopapular brown-violaceous lesions, purple nodules; papilledema JAAD

Winchester syndrome

Werner's syndrome Xeroderma pigmentosum – acute sunburn, persistent erythema, freckling - initially discrete, then fuse to irregular patches of hyperpigmentation, dryness on sun-exposed areas; with time telangiectasias and small angiomas, atrophic white macules develop; vesiculobullous lesions, superficial ulcers lead to scarring, ectropion; multiple malignancies(basal cell carcinoma, squamous cell carcinoma, keratoacanthoma, melanoma); photophobia, conjunctivitis, ectropion, symblepharon, neurologic abnormalities Adv Genet 43:71–102, 2001; Hum Mutat 14:9–22, 1999; Mol Med Today 5:86–94, 1999; Derm Surg 23:447–455, 1997; Dermatol Clin 13:169–209, 1995; Recent Results Cancer Res 128:275–297, 1993; AD 123:241–250, 1987; Ann Int Med 80:221–248, 1974; XP variant AD 128:1233–1237, 1992

Hyperpigmentation, Segmental or Zosteriform

TOXINS Arsenic – diffuse pigmentation, especially of trunk; with depigmentation yielding rain-drop appearance(freckled raindrop pattern) (“raindrops on a dusty road”); arsenic toxicity due to contaminated ground water consumption; especially in Bangladesh and West Bengal, India; also in India, Argentina, China, Chile, Thailand, and Mexico SkinMed 11:211–216, 2013; Dermatol Clinics 29:45–51, 2011; Cutis 80:305–308, 2007; J Envir Sci Health Part A Tox Hazard Subst Environ Eng 38:141:163, 2003;; macular bronze pigmentation of the trunk; stippled hyper- and hypopigmentation JAAD 39:524–525, 1008; JAAD 38:179–185, 1998; darkening of hair BJD 146:325–329, 2002; paronychial hyperpigmentation BJD 149:757–762, 2003 Mustard gas exposure AD 129:245, 1993 PCB exposure – brown-gray nails

TRAUMA Biting of buccal mucosa - symmetric hyperpigmentation of chin BJD 82:40–41, 1970 Chewing trauma in mentally disabled Arch Dermatol Syphilol 65:458–463, 1952 Frictional hyperpigmentation(melanosis) JAAD 77:591–605, 2017; JAAD 65:689–697, 2011; JAAD 42:442–445, 2000; frictional hyperpigmentation of the extensor surfaces Cutis 75:349–355, 2005 Hypothermia – pink or brown discoloration with blisters over joints JAAD 64:811–824, 2011 Intravenous drug abuse – tourniquet hyperpigmentation, sooting tattoos, track marks JAAD 69:135–142, 2013; BJD 150:1–10, 2004 Mitten line pigmentation in infancy Ped Derm 27:401–402, 2010 Radiation dermatitis, acute Acta DV 49:64–71, 1969; chronic JAAD 54:28–46, 2006 Sock line pigmentation of infancy AD 143:428–430, 2007; BJD 157:1063–1064, 2007 Sympathectomy, surgical – localized hyperpigmentation Clin Exp Dermatol 5:349–350, 1980

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purpuric eruption, Majocchi’s, and others - hemosiderin lichen aureus Post-phlebitic syndrome – pain, edema, night cramps, hemosiderin deposition, dermatitis Phlebology 11:2–5, 1996 Stewart-Bluefarb syndrome – arteriovenous malformation of leg with multiple fistulae and port wine stain-like purplish lesions(Mali’s acroangiodermatitis/pseudo-Kaposi’s sarcoma) – brown macules, purple nodules and plaques, edema, varicose veins, hypertrichosis, cutaneous ulcers, enlarged limb JAAD 65:893–906, 2011 Urticarial vasculitis Clin Rev Allergy Immunol 23:201–216, 2002 Venous malformation – patchy discoloration Ped Derm 30:534–540, 2013 Venous stasis dermatitis – hemosiderin NEJM 355:488–498, 2006

HYPERPIGMENTATION, SEGMENTAL OR ZOSTERIFORM AUTOIMMUNE DISEASES Lupus erythematosus, discoid – linear, Blaschko Dermatol Online J 19:18960, 2013; Postepy Dermatol Alergol 34:177–179, 2017 Morphea, linear JAAD 59:385–396, 2008

CONGENITAL LESIONS Congenital segmental dermal melanocytosis AD 128:521–525, 1992

DRUG-INDUCED Fixed drug eruption, linear

EXOGENOUS AGENTS Silver nitrate stain

VASCULAR DISEASES

Walnut stain

Angiosarcoma of the breast post-irradiation for breast cancer – hyperpigmentation of breast with late thickening, edema, or induration JAAD 49:532–538, 2003

INFECTIONS AND INFESTATIONS

Arteritis - cutaneous arteritis – round, linear, reticulated hyperpigmentation JAAD 49:519–522, 2003

Erythrasma

Cerebral large venous malformations(cavernomas) associated with en coup de sabre (hyperpigmentation and atrophy) Ped Derm 37:237–238, 2020

Tinea versicolor

Lipodermatosclerosis – chronic venous insufficiency with hyperpigmentation, induration, inflammation Lancet ii:243–245, 1982

INFLAMMATORY DISEASES

Macular arteritis – reticulated purpuric macules mimicking pigmented purpuric eruption Ped Derm 26:93–95, 2009; asymptomatic hyperpigmented macules of legs in black patients JAAD 52:364– 366, 2005; JAAD 49:519–522, 2003 Macular lymphocytic arteritis – hyperpigmented macules of legs JAMADerm 153:815–816, 2017; JAAD 73:1013–1020, 2015; Am J Dermatopathol 35:213–219, 2013; JAAD 49:519–522, 2003; J Cut Pathol 42:416–419; J Eur Acad Dermatol Venereol doi 10.1111/ jdv12941 Pigmented purpuric eruptions including lichenoid pigmented purpuric eruption of Gougerot and Blum, Schamberg's pigmented

Herpes zoster - post-zoster hyperpigmentation

Hair repigmentation of scalp at site of herpes zoster AD 146:569– 570, 2010

NEOPLASTIC DISEASES Acquired nevus of Ota Becker's nevus – giant bilateral Becker’s nevi Ped Derm 25:47–51, 2008; Becker’s nevus over entire leg with lipoatrophy JAMA Derm 149:1115, 2013; face and oral mucosa Ped Derm 29:670–671, 2012 Cafe au lait macules   Ataxia telangiectasia JAAD 10:431–438, 1984

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  Bloom’s syndrome  Café au lait macules and pulmonary stenosis(Watson’s syndrome)   Café au lait macules and ring chromosome 11  Café au lait macules and temporal dysrhythmia(Verner’s syndrome)   Cardio-facio-cutaneous syndrome AD 129:446–447, 1993  Neurofibromatosis   Segmental   Solitary

Lichen planus pigmentosus SkinMed 11:96–103, 2013; Bull Soc Fr Dermatol Syphiligr 42:894–898, 1935; Bull Soc Fr Dermatol Syphiligr 42:792–794, 1935

Dermatofibrosarcoma protuberans

Segmental pigmentation disorder BJD 162:1337–1341, 2010; Acta DV 63:167–169, 1983

Congenital nevocytic nevus Flag-like hypermelanotic nevus J Eur Acad DV 29:2088–2099, 2015 Lentiginosis Am J Dermatopathol 14:323–327, 1992; with ocular involvement JAAD 44:387–390, 2001; partial unilateral lentiginosis JAAD 44:387–390, 2001; agminated lentiginosis Ped Derm 11:241–245, 1994 Lentiginous nevus BJD 98:693–698, 1978 Linear rhabdomyomatous mesenchymal hamartoma – unilateral facial depressions, atrophy, and hyperpigmentation of chin Ped Derm 36:716–717, 2019 Melanocytic nevi - congenital, Spitz, blue, speckled lentiginous Acta DV 78:378–380, 1998; JAAD 27:853–854, 1992; congenital agminated segmental nevi BJD 133:315–316, 1995; congenital melanocytic nevus Melanoma JAAD 32:854–857, 1995 Nevus of Ito(nevus fuscoceruleus acromio-deltoideus) Tohou J Exp Med 60:10–20, 1954 Nevus of Ota(nevus fuscoceruleus ophthalmomaxillaris) – blue or gray Clin in Derm 37:515, 2019; BJD 67:317–319, 1955 Nevus spilus(zosteriform lentiginous nevus)(speckled and lentiginous nevus) Curr Prob in Derm VII:143–198, 1995; AD 107:902– 905, 1973 Segmental lentiginosis(zosteriform lentiginous nevus) Am J Dermatopathol 14:323–327, 1992 Speckled and lentiginous nevi - large segmental speckled lentiginous nevi JAAD 64:1190–1193, 2011 Smooth muscle hamartoma Spitz nevi, agminated

PHOTODERMATOSES Berloque dermatitis Ephelides

PRIMARY CUTANEOUS DISEASES Acanthosis nigricans, nevoid – unilateral and localized Int J Dermatol 30:452–453, 1991 Acquired dermal melanocytosis(acquired nevus of Ota-like macules) JAAD 43:934–936, 2000 Atrophoderma of Moulin (linear atrophoderma of Moulin) – unilateral acquired atrophic pigmented band-like lesions following Blaschko’s lines JAMADerm 156:583–584, 2020; Ann DV 119:729–736, 1992 Lichen planus – multidermatomal, zosteriform Int J Dermatol 58:343–344, 2019

Partial unilateral lentiginosis JAAD 44:387–390, 2001; JAAD 29:693–695, 1993 Pigmentary mosaicism Ped Clin NA 57:1121–1129, 2010 Progressive cribriform and zosteriform hyperpigmentation Australasian J Dermatol 59:68–69, 2018; AD 114:98–99, 1978 Segmental dyschromatosis

Zosteriform reticulate hyperpigmentation BJD 121:280, 1989; in children BJD 117:503–17, 1987; AD 114:98–99, 1978; unilateral dermatomal pigmentary dermatosis Semin Cut Med Surg 16:72–80, 1997; JAAD 27:763–764, 1992

SYNDROMES Atrophoderma of Moulin – unilateral acquired atrophic pigmented band-like lesions following Blaschko’s lines Int J Dermatol 39:846–852, 2000; BJD 135:277–279, 1996; Ann DV 119:729–736, 1992 Familial progressive hyperpigmentation Gastrocutaneous syndrome Happle-Tinschert syndrome – segmental basaloid follicular hamartomas; ipsilateral hypertrichosis; hypo- and hyperpigmentation; linear atrophoderma; osseous, dental, and/or cerebral defects BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221–225, 2009; Acta DV 88:382–387, 2008 LEOPARD(multiple lentigines) syndrome McCune-Albright syndrome Neurofibromatosis, segmental Neurology 56:1433–1443, 2001; JAAD 37:864–869, 1997; Ped Derm 10:43–45, 1993; JAAD 23:866–869, 1990; AD 113:837–838, 1977 Nevus spilus syndrome – ipsilateral hyperhidrosis, muscular weakness, dysesthesia Eur J Dermatol 12:133–135, 2002 Ross syndrome – segmental anhidrosis, depressed deep tendon reflexes, tonic pupils, hyperpigmented body J Family Med Prim Care 8:1500–1503, 2019 Russell-Silver syndrome Tuberous sclerosis Westerhof's syndrome Xeroderma pigmentosum

VASCULAR DISEASES Lymphangioma circumscriptum(lymphatic malformation) Pigmented purpuric eruptions - lichen aureus Cutis 69:145–148, 2002; Hautarzt 49:135–138, 1998; Int J Derm 30:654–657, 1991; Int J Dermatol 30:654–655, 1991; Dermatologica 180:93–95, 1990; Hautarzt 40:373–375, 1989; unilateral Schamberg’s disease BJD 144:190–191, 2001

HYPERPIGMENTED LESIONS, DISCRETE ANNULAR

Hyperpigmented Lesions, Discrete Annular

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – to EKG leads Bullous pemphigoid – figurate lesions, resolved Dermatitis herpetiformis

Tattoo pigment fanning – periorbital hyperpigmentation Cutis 68:53–55, 2001 Vitamin K allergy(injection) J Cut Med Surg 4:164–168, 2000; BJD 95:653–656, 1976

Lichen planus pemphigoides - personal observation

EXOGENOUS

Linear IgA disease

Disinfectant – ortho-phthalaldehyde AD 143:670, 2007

Lupus erythematosus - discoid lupus erythematosus NEJM 269:1155–1161, 1963; lupus profundus; neonatal LE JAAD 40:675–681, 1999; Clin Exp Rheumatol 6:169–172, 1988; subacute cutaneous LE; bullous dermatosis of SLE JAAD 27:389–394, 1992; Arthritis Rheum 21:58–61, 1978; subacute

Tar burns

Morphea JAAD 59:385–396, 2008; guttate morphea - personal observation

CONGENITAL Pre-auricular skin defects AD 133:1551–1554, 1997

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INFECTIONS AND INFESTATIONS AIDS - pruritic papular eruption with HIV in Uganda JAMA 292:2614–2621, 2004 Borrelia burgdorferi – morphea-like lesions of annular hyperpigmentation JAAD 48:376–384, 2003 Cydnidae(burrowing bug) – burrowing bug pigmentation; round brown macules of thumb or soles JAMADerm 151:232–233, 2015

Congenital smooth muscle hamartoma Curr Prob Derm 14:41–70, 2002

Epidermodysplasia verruciformis - hypopigmented guttate macules in immunocompromised patients JAAD 76:1161–1175, 2017; JAAD 74:437–451, 2016

Transient neonatal pustular melanosis Int J Dermatol 18:636–638, 1979; J Pediatr 88:831–835, 1976

Erythrasma, disciform Herpes simplex virus infection Impetigo – post-inflammatory hyperpigmentation

DRUG-INDUCED Amiodarone - personal observation AZT pigmentation Antimalarial pigmentation(atabrine) Bleomycin Chemotherapy - under adhesive bandages after chemotherapy -linear, annular and diffuse hyperpigmentation Ped Derm 8:231–235, 1991 Clofazamine pigmentation within lesions of Hansen's disease Dactinomycin – flexural cutaneous necrosis with post-inflammatory hyperpigmentation AD 142:1660–1661, 2006 Doxorubicin(liposomal) – melanotic macules AD 136:1475–1480, 2000 Fixed drug eruptions JAMA 312:2281–2282, 2014 Gold – chrysiasis – periorbital hyperpigmentation Cutis 68:53–55, 2001 Hydroxychloroquine - personal observation Insulin reactions – itchy nodule evolves into hyperpigmentation Int J Derm 23:567–583, 1984 Minocycline hyperpigmentation – blue-gray, brown Pegylated interferon injection sites MLH Scler 24:231–233, 2018; JAAD 60:882–883, 2009 Polyethylene glycol-coated liposomal doxorubicin - melanotic macules AD 136:1475–1480, 2000 Propranolol – annular telangiectatic perivascular angiomatosis – red to violaceous hyperpigmented annular plaques with central clearing and radial telangiectasia BJD 169:1369–1371, 2013 Prostaglandin F2alpha analog(latanoprost) eyedrops – hyperpigmentation and trichomegaly(eyelash hypertrichosis) JAAD 44:721–723, 2001; Cutis 67:109–110, 2001 Stem cell factors, injected

Leishmaniasis – scar with thin pale center over ulcer site surrounded by hyperpigmented halo JAAD 60:897–925, 2009; kala azar Millipede defensive secretions – periorbital hyperpigmentation JAAD 50:819–842, 2004 Pinta – secondary – hyperpigmented macules JAAD 54:559–578, 2006; tertiary(late phase) - gray, steel, ashy, bluish spotted hyperpigmentation Stinkbug staining(Halyomorpha halys) – discrete annular hyperpigmentation Cutis 97:89, 115, 2016 Tinea nigra palmaris(plantaris) - Phaeoannelomyces werneckii, Hortaea werneckii; Stenella araguata Clin in Derm 37:447–467, 2019; Cutis 87:229, 232, 2011; Ped Derm 20:315–317, 2003; Cutis 64:199–201, 1999; Ped Derm 15:233–234, 1998; AD 11:904–905, 1975 Tinea versicolor Yaws

INFILTRATIVE DISEASES Amyloidosis AD 123:1557–1562, 1987; macular amyloid - periorbital hyperpigmentation Clin Exp Derm 8:195–197, 1983; macular amyloidois as part of primary localized cutaneous amyloidosis – mutation in OSMR(oncostatin M receptor beta) AD 145:695–699, 2009; lichen amyloidosis The Dermatologist October 2015 :pp.48–50 Pretibial myxedema Mastocytosis – urticaria pigmentosa Acta DV(Stockh) 42:433–439, 1962 Xanthogranulomas, periorbital(adult-onset asthma with periocular xanthogranulomas) – hyperpigmented indurated nodules of upper and lower eyelids(swollen eyelids); associated with asthma AD 147:1230–1231, 2011; Arch Pathol Lab Med 133:1994–1997, 2009;

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Br J Ophthalmol 90:602–608, 2006; Trans Am Ophthalmol Soc 91:99–129, 1993

INFLAMMATORY DISEASES Interstitial granulomatous dermatitis - annular polycyclic hyperpigmented plaques associated with coccidioidomycosis BJD 174:881– 884, 2016 Post-inflammatory hyperpigmentation – erythema multiforme Sarcoid - annular plaques with peripheral hyperpigmentation of scalp The Dermatologist, January 2016, pp.47–48, 50

METABOLIC DISEASES Androgen excess – hyperpigmentation of areolae, perineum Diabetes mellitus – diabetic dermopathy(annular atrophic patches of legs) JAAD 58:447–451, 2008; Am J Med Sci 251:570–575, 1966; AD 93:282–286, 1966; AD 92:625–634, 1965; Acta Med Scand 176(Suppl)1–75, 1964 Gaucher's disease GM-1 gangliosidosis - atypical Mongolian spots Necrobiosis lipoidica diabeticorum Int J Derm 33:605–617, 1994; JAAD 18:530–537, 1988 Pancreatic panniculitis – heal with post-inflammatory hyperpigmented spots; JAAD 34:362–364, 1996; Arthritis Rheum 22:547– 553, 1979; Am J Gastroenterol 83:177–179, 1988 Vitamin B12 deficiency - personal observation

LEOPARD syndrome, central facial, Peutz-Jeghers syndrome, Cronkhite-­Canada syndrome; genital lentigines in the presence of lichen sclerosus JAAD 50:690–694, 2004 Lentiginous nevoid anomaly Lentigo Lymphoma, including cutaneous T cell lymphoma An Bras Dermatol 92(Suppl 1)92–94, 2017; Dermatology 192:360–363, 1996 Lymphocytoma cutis Melanocytic nevus; congenital melanocytic nevus - cobblestoned, cerebriform, localized hypertrichosis, hyperpigmented discrete annular plaque Ped Derm 32:23–27, 2015; JAAD 68:441–451, 2013; BJD 160:387–392, 2009; congenital melanocytic nevus of scalp with dark annular patch of hair NEJM 367:362, 2012; with white halo congenital melanocytic nevus NEJM 370:262, 2014; eruptive melanocytic nevi in transplant patients JAAD 56:898–900, 2007; JAAD 49:1020–1022, 2003; scalp nevus NEJM 367:362, 2012; multiple congenital pigmented nevi – multiple annular hyperpigmented macules BJD 169:374–383, 2013; genital nevi in children JAAD 70:429–434, 2014 Melanoma – acral lentiginous melanoma BJD 155:561–569, 2006; melanoma in situ; superficial spreading melanoma; melanoma of the vulva JAAD 50:293–298, 2004; Int J Gynecol Cancer 11:359–364, 2001; Cancer 86:1273–1284, 1999; metastatic melanoma - periorbital gray pigmentation Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.83 Mongolian spot Neurofibroma – pigmented plexiform neurofibroma JAAD 56:862– 868, 2007

Wilson's disease

Nevus of Ito

NEOPLASTIC

Nevus spilus(speckled and lentiginous nevus) JAAD 61:337–341, 2009; Ped Derm 13:250–252, 1996; AD 114:895–896, 1978

Actinic keratosis JAAD 68:647–653, 2013

Pagetoid dyskeratosis JAMA Derm 149:109–111, 2013

Atypical melanocytic hyperplasia

Periaxillary and perigenital pigmentation

Basal cell carcinoma

Plasmacytomas – primary cutaneous plasmacytosis - brown-red macules; polyclonal hypergammaglobulinemia and lymphadenopathy JAAD 56:S38–40, 2007; Dermatol 189:251, 1994; JAAD 31:897–900, 1994; AD 122:1314, 1986; Atlantic Derm Meeting, May 1994; Atlantic Derm Meeting, May 2000

Becker's nevus Bowen's disease AD 129:1043–1048, 1993; Cancer 57:823–836, 1986 Cafe au lait macule

Nevus of Ota

Castleman's disease

Porokeratosis with or without Bowen's disease AD 142:1059–1064, 2006

Congenital melanocytic nevus

Seborrheic keratosis - personal observation

Dermal dendrocyte hamartoma – medallion-like; annular brown or red congenital lesion of central chest with slightly atrophic wrinkled surface AD 142:921–926, 2006; JAAD 51:359–363, 2004

Solar lentigo

Dermatofibrosarcoma protuberans Precalcaneal congenital fibrolipomotous hamartoma – annular hyperpigmented patch with cigarette paper wrinkling; resembles nevus lipomatosis superficialis and fibrous hamartoma of infancy AD 148:1073–1078, 2012 Granular cell Schwannoma Kaposi's sarcoma in AIDS JAAD 22:1237–1250, 1990

Spitz nevi arising in nevus spilus JAMA Derm 149:1077–1080, 2013 Squamous cell carcinoma, in situ - personal observation

PARANEOPLASTIC DISEASES Glucagonoma – necrolytic migratory erythema Am J Dermatopathol 41:e29–32, 2019 Necrobiotic xanthogranuloma with paraproteinemia

Keloid Large cell acanthoma(macule) Cutis 47:97–100, 1991

PHOTODERMATITIS

Large plaque parapsoriasis

Ephelides(freckles) – autosomal dominant

Lentigines - generalized lentiginosis, zosteriform, eruptive,

Lichen planus actinicus Dermatol Online J Jan 2007 Phytophotodermatitis J Emerg Med 17:235–237, 1999

Hyperpigmented Lesions, Discrete Annular Solar elastosis Sunburns

PRIMARY CUTANEOUS DISEASES Acanthosis nigricans Acquired bilateral telangiectatic macules JAMADerm 150:974–977, 2014 Acquired epidermodysplasia verruciformis in AIDS - personal observation Acquired nevus of Ota-like macule - personal observation Annular erythema of infancy JAAD 14:339–343, 1986 Annular lichenoid dermatitis of youth – red-brown annular plaques with hypopigmented centers Ped Derm 27:584–585, 2010; JAAD 49:1029, 2003 Atrophoderma of Moulin - personal observation Atrophoderma of Pasini and Pierini Dermatol 190:203–206, 1995; JAAD 30:441–446, 1994; Int J Derm 10:643–645, 1984 Chromhidrosis – black, violet, blue, brown, yellow, green, rarely red Eosinophilic annular erythema J Eur Acad DV 31:1916–1923, 2017 Epidermolysis bullosa simplex herpetiformis(Dowling-Meara) JAAD 28:859–861, 1993 Erythema annulare centrifugum – hyperpigmentation, rarely Bull Soc Fr Dermatol Syphiligr 71:450–452, 1964 Erythema dyschromicum perstans(ashy dermatosis) - blue-gray patches with red raised margins; coalesce over face, trunk, and extremities; hypo- and hypermelanotic macules resembling late pinta J Drugs in Dermatol 12:819–820, 2013; Cutis 68:25–28, 2001; AD 124:1258–1260, 1988; Int J Derm 24:630–633, 1985 Erythema elevatum diutinum – giant annuli BJD 143:415–420, 2000; AD 132:1524–1525, 1996 Granuloma annulare, disseminated Frontal fibrosing alopecia – skin colored facial papules, follicular red dots, perifollicular and diffuse erythema with reticulated pattern, pigmented macules JAAD 73:987–990, 2015 Hyperpigmented macules of palms and soles in blacks Int J Dermatol 18:222–225, 1979 Idiopathic eruptive macular hyperpigmentation – light brown non-­confluent macules 3–25 mm of neck, trunk, or extremities(distinguished from erythema dyschromicum perstans) Ped Derm 32:733–734, 2015; AD 146:1301–1306, 2010; BJD 157:839–840, 2007; Indian J DV Leprol 73:402–405, 2007; J Dermatol 31:440–441, 2004; JAAD 49:S280–282, 2003; JAAD 44: 351–353, 2001; Ped Derm 13:274–277, 1996; JAAD 11:159, 1984; Ann DV 105:177–182, 1978 Lichen amyloid Lichen planus – lichen planus in blacks annular atrophic lichen planus Dermatology 195:402–403, 1997; lichen planus actinicus – annular blue-gray or brown hyperpigmented plaques Cutis 72:377–381, 2003; hypertrophic lichen planus Lichen planus pigmentosus – annular pigmented macules on background of erythema JAMADerm 154:717–718, 2018 Lichen sclerosus et atrophicus Notalgia paresthetica

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Periorbital hyperpigmentation(infraorbital dark circles; raccoon eyes) BJD 160:1022–1025, 2009;  Extension of pigmentary demarcation lines of face J Clin Aesthet Dermatol 9:49–55, 2016  Familial AD 100:169–174, 1969; Cutis 5:579, 1969   Lichen planus   Mercurial preparations – blue or gray-brown  Post-traumatic  Post-inflammatory hyperpigmentation – atopic or allergic contact dermatitis, lichen planus pigmentosus, fixed drug eruption  Prostaglandin analogues – Latisse, latanoprost, bimatoprost Ophthalmology 113:1961–1967, 2006   Psoralens in cosmetics   Silver preparations – blue or gray-brown   Tear trough depression Pityriasis rotunda – large annular hyperpigmented scaly patches; may be paraneoplastic phenomenon; or with leprosy AD 144:1509– 1514, 2008; Ped Derm 19:200–203, 2002; JAAD 31:866–871, 1994; JAAD 14:74–78, 1986; BJD 76:223–227, 1964 Pityriasis rubra pilaris – PRP type V – hyperkeratotic scaly patches of dorsal hands, annular brown macules, red patches; CARD14 mutation(caspase recruitment domain family 14) JAMADerm 153:66–70, 2017 Pseudo-acanthosis nigricans Psoriasis Sock line hyperpigmentation – annular circumferential pigmentation AD 143:428–430, 2007; JAAD 2:S162–164, 2007 Subcorneal pustular dermatosis of Sneddon-Wilkinson – pustules which expand to annular and serpiginous lesions with scaly edge; heal with hyperpigmentation J Dermatol 27:669–672, 2000; Cutis 61:203–208, 1998; JAAD 19:854–858, 1988; BJD 68:385–394, 1956 Terra firme

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis Neurotic excoriations

SYNDROMES Acro-dermato-ungual-lacrimal-tooth syndrome(ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, superficial blisters and desquamation of hands and feet; lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears hooked nose, sparse thin blond hair, frontal alopecia, hypohidrosis, lacrimal duct atresia, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene(encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes BJD 172:276–278, 2015; Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993 Ataxia telangiectasia – hyperpigmented macules, hypopigmented macules, café au lait macules BJD 144:369–371, 2001 Bannayan-Riley-Ruvalcaba- Zonana syndrome – hemangiomas, genital hyperpigmentation, supernumerary nipples AD 132:1214– 1218, 1996; Am J Med Genet 44:307–314, 1992 Cafe au lait macules(CALMs) and temporal dysrhythmia

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CANDLE syndrome(chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips(thick lips), lipoatrophy of cheeks and arms, chondritis with progressive ear and saddle nose deformities, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, splenomegaly, protuberant abdomen JAAD 62:489–495, 2010 Centrofacial lentiginosis Cronkhite-Canada syndrome - lentigo-like macules of face, extremities, and diffuse pigmentation of palms; gastrointestinal polyposis, malabsorption, alopecia, dystrophic nails AD 135:212, 1999; Cutis 61:229–232, 1998

Terminal osseous dysplasia and pigmentary defects – regional skin hypoplasia; X-linked dominant; digital fibromas, punched out pigmentary anomalies of face and scalp, eye anomalies(colobomas, hypertelorism) Ped Derm 24:280–284, 2007; Am J Med Genet 124A:202–208, 2004 Tuberous sclerosis - CALM Watson's syndrome - CALM and pulmonic stenosis Westerhof syndrome - hypo and hypermelanotic macules on the trunk and extremities; hereditary congenital hypopigmented and hyperpigmented macules BJD 161:1399–1400, 2009; Curr Prob in Derm VII:143–198, 1995; AD 114:931–936, 1978 Wells’ syndrome - personal observation

Familial multiple cafe au lait macules AD 130:1425–1426, 1994

Xeroderma pigmentosum – acute sunburn, persistent erythema, freckling - initially discrete, then fuse to irregular patches of hyperpigmentation, dryness on sun-exposed areas; with time telangiectasias and small angiomas, atrophic white macules develop; vesiculobullous lesions, superficial ulcers lead to scarring, ectropion; multiple malignancies; photophobia, conjunctivitis, ectropion, symblepharon, neurologic abnormalities Adv Genet 43:71–102, 2001; Hum Mutat 14:9–22, 1999; Mol Med Today 5:86–94, 1999; Derm Surg 23:447–455, 1997; Dermatol Clin 13:169–209, 1995; Recent Results Cancer Res 128:275–297, 1993; AD 123:241–250, 1987; Ann Int Med 80:221–248, 1974; XP variant AD 128:1233–1237, 1992

Fanconi’s anemia – freckle-like hyperpigmentation in sun-exposed areas, abdomen, flexures, and genitals Dermatol Clin 13:41–49, 1995

TOXINS

Dermatopathia pigmentosa reticularis – autosomal dominant; dark areolae, reticulate pigmentation of trunk, neck, and proximal extremities, alopecia, nail changes(mild onychodystrophy), palmoplantar hyperkeratosis, loss of dermatoglyphics, hyperpigmented tongue, hypo- or hyperhidrosis, non-scarring blisters of dorsal hands and feet, thin eyebrows, Ped Derm 24:566–570, 2007; J Dermatol 24:266–269, 1997; JAAD 26:298–301, 1992; AD 126:935–939, 1990; Dermatol Wochenschr 138:1337, 1958

Hermansky-Pudlak syndrome – freckling in sun-exposed skin JAAD 19:217–255, 1988 Laugier-Hunziker syndrome AD 143:631–633, 2007 LEOPARD syndrome Localized hereditary pruritus Moynahan’s syndrome – lentigines, congenital mitral stenosis, dwarfism, mental retardation, genital hypoplasia Multiple mucosal neuroma syndrome(MEN IIB) - perioral or periocular hyperpigmentation, lentigines, or freckles NAME/LAMB syndromes; MEN IIA - hyperkeratosis and hyperpigmentation in localized pruritic patch between the scapulae JAAD 42:939–969, 2000 Neurofibromatosis type I – axillary freckling(Crowe’s sign) JAAD 61:1–14, 2009; J Med Genet 26:712–721, 1989; Ann Int Med 61:1142–1143, 1964; CALMs Peutz-Jeghers syndrome – lentigines; brown pigmented bands of nails Phakomatosis pigmentokeratotica – organoid nevus with nevus spilus SkinMed 11:125–128, 2013 Phakomatosis spilorosea(form of phakomatosis pigmentovascularis) – nevus spilus with a telangiectatic nevus AD 141:385–388, 2005 Piebaldism Clin in Dermatol 33:367–368, 2015 Proteus syndrome – port wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation Am J Med Genet 27:87–97, 1987; Pediatrics 76:984–989, 1985; Eur J Pediatr 140:5–12, 1983

Arsenic – arsenical pigmentation; large annular hyperpigmented patch BJD 159:169–174, 2008

TRAUMA Cardioversion(defibrillation) – hypopigmented, atrophic, telangiectatic, crusted erythematous plaque of back with rim of hyperpigmentation; delayed onset of years AD 145:1411–1414, 2009 Hypothermia – pink or brown discoloration with blisters over joints JAAD 64:811–824, 2011 Mechanical trauma Radiation dermatitis

VASCULAR Arteritis - cutaneous arteritis – round, linear, reticulated hyperpigmentation JAAD 49:519–522, 2003 Atrophie blanche Capillary malformation-arteriovenous malformation syndrome(CMAVM syndrome) – annular brown lesions; RASA1 mutation; vascular stains and cardiac failure; multiple capillary malformations, Parkes-Weber syndrome, pink stain overlying arteriovenous malformation; multiple infantile hemangiomas, pink patches Ped Derm 33:570–584, 2016; Ped Derm 32:128–131, 2015; Ped Derm 32:76–84, 2015; Am J Hum Genet 6:1240–1249, 2003; Acta DV 3:202–211, 1922 Cutaneous polyarteritis nodosa – inflammatory red plaque with central hyperpigmentation and peripheral nodules JAAD 60:320– 325, 2009 Erythema induratum Lipodermatosclerosis

Hypertrichosis, Generalized Macular lymphocytic arteritis JAAD 73:1013–1020, 2015; Am J Dermatopathol 35:213–219, 2013; JAAD 49:519–522, 2003; J Cut Pathol 42:416–419; J Eur Acad Dermatol Venereol doi 10.1111/ jdv12941

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Transient congenital hypertrichosis universalis Clin Genet 57:157– 158, 2000 Universal hypertrichosis (form of congenital generalized hypertrichosis)

Pigmented purpuric eruptions, including lichen aureus Stewart-Bluefarb syndrome – arteriovenous malformation of leg with multiple fistulae and port wine stain-like purplish lesions(Mali’s acroangiodermatitis/pseudo-Kaposi’s sarcoma) – brown macules, purple nodules and plaques, edema, varicose veins, hypertrichosis, cutaneous ulcers, enlarged limb JAAD 65:893–906, 2011 Urticarial vasculitis Clin Rev Allergy Immunol 23:201–216, 2002

HYPERTRICHOSIS, GENERALIZED

DRUG-INDUCED Acetazolamide JAAD 48:161–179, 2003 ACTH Anabolic steroids Benoxaprofen – pseudo-PCT J R Soc Med 76:525–527, 1983 Chemotherapy – hypertrichosis lanuginosa Clin Oncol(R Coll Radiol) 4:267–268, 1992 Corticosteroids - systemic or topical Cyclosporine JAAD 48:161–179, 2003; JAAD 44:932–939, 2001

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Danazol

Dermatomyositis – also in Mexicans/Indians JAAD 31:383–387, 1994; longstanding dermatomyositis - lipodystrophy-like appearance(hirsutism, loss of subcutaneous tissue, acanthosis nigricans); congenital dermatomyositis; juvenile dermatomyositis JAAD 33;691, 1995; JAAD 31:383–387, 1994

Epidermal growth factor receptor inhibitors – cetuximab and panitumumab; erlotinib and gefitinib; lapatinib; canertinib; vandetanib – hirsutism JAAD 80:1179–1196, 2019; JAAD 72:203–218, 2015

Lupus erythematosus Clin Rheumatol 19:245–246, 2000

Fenoterol JAAD 56:S45–47, 2007

PLAID(PLCG2-associated antibody deficiency and immune dysregulation) – hypertrichosis in infancy; evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAMADerm 151:627–634, 2015

Hexachlorobenzene

Polymyositis – acquired hypertrichosis lanuginosa Int J Derm 32:227–228, 1993

CONGENITAL DISORDERS Congenital generalized terminal hypertrichosis with gingival hyperplasia Ped Derm 19:114–118, 2002 Congenital hypertrichosis lanuginosa(congenital generalized hypertrichosis)(hypertrichosis lanuginosa congenita) Ped Derm 25:483–484, 2008; BJD 157:1087–1092, 2007; Ped Derm 19:64– 66, 2002; J Genet Humaine 17:10–13, 1969 Congenital hypertrichosis terminalis Ped Derm 29:219–220, 2012; with gingival hyperplasia Ped Derm 19:114–118, 2002; with gingival fibromatosis Indian J Derm Res 28:457–460, 2017 Congenital macrogingivae – profuse hypertrichosis of lower face, trunk, and extremities with acromegalic features Plast Reconstr Surg 27:608–612, 1962 Preterm neonate - lanugo of face, limbs, and trunk AD 83:175–198, 1961 Smooth muscle hamartoma – generalized congenital smooth muscle hamartoma – inguinal and sacral redundancy with hypertrichosis Ped Derm 25:236–239, 2008

Diazoxide Ann DV 115:191–193, 1988; BJD 93:707–711, 1975

Erythropoietin Am J Kidney Dis 18:619, 1991

Interferon BJD 157:1087–1092, 2007 Isotretinoin Latanoprost JAAD 48:161–179, 2003; JAAD 44:721–723, 2001 Minoxidil – generalized hypertrichosis with topical minoxidil BJD 136:118–120, 1997; face, shoulders, and extremities South Med J 70:442–443, 1977; generalized hypertrichosis in child with skin to skin exposure to adult using minoxidil Ped Derm 31:520–522, 2014; congenital generalized hypertrichosis due to maternal ingestion of minoxidil Pediatrics 79:434–436, 1987; piggy back acquired hypertrichosis Ped Derm 31:520–522, 2014 Mycophenylate mofetil Omeprazole Ped Derm 35:e212–214, 2018 Oral contraceptives Penicillamine Phenytoin JAAD 48:161–179, 2003 Phenothiazine Psoralens - PUVA therapy Cutis 41:199–202, 1988; Arch Dermatol Res 278:82–83, 1985; BJD 109:657–660, 1983 Secukinumab Dermatol Ther 32:e12894, May 2019 Streptomycin JAAD 48:161–179, 2003 Tamoxifen Testosterone proprionate Thiouracil Verapamil Lancet 338(8776)1215–1216, 1991 Zidovudine JAAD 46:284–293, 2002; AIDS 5:1395–1396, 1991

520 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

EXOGENOUS AGENTS Organochlorine exposure(agent orange) – chloracne with comedones, gray dyschromia, hypertrichosis, folliculitis, porphyria cutanea tarda, melanoma and non-melanoma skin cancer, non-Hodgkin’s lymphoma, dermatofibrosarcoma protuberans JAAD 74:143–170, 2016

Giant nevoid hypertrichosis Ped Derm 19:64–66, 2002

PARANEOPLASTIC DISORDERS

Post-mumps

Hypertrichosis lanuginosa acquisita(malignant down) - 41 cases; lung, colon carcinomas most common; also breast, gall bladder, uterus, urinary bladder; if accompanied by acanthosis nigricans; the malignancy is always an adenocarcinoma; hypertrophy of tongue papillae and glossitis often present; usually metastatic disease present at time of diagnosis of hypertrichosis lanuginosa BJD 157:1087–1092, 2007; JAAD 56:S45–47, 2007; J Surg Oncol 68:199–203, 1998; AD 122:805–808, 1986; Med Times Gazette 2:507, 1865

INFLAMMATORY DISEASES

PRIMARY CUTANEOUS DISEASES

Cerebral abnormalities JAAD 48:161–179, 2003

Epidermolysis bullosa, dystrophic

Multiple sclerosis Ped Derm 18:57–59, 2001

Familial hypertrichosis - personal observation

INFECTIONS HIV infection, advanced Post-encephalitis Ped Derm 18:57–59, 2001

Ichthyosis en confetti – hypertrichosis over erythrodermic areas JAMADerm 151:64–69, 2015

METABOLIC DISEASES Acromegaly Central nervous system-related causes – encephalitis, head trauma, multiple sclerosis, shock, anorexia, hyperostosis interna Am J Clin Dermatol 3:617–627, 2002 Cushing’s syndrome Hypothyroidism – back, shoulders, and extensor extremities Ped Derm 22:447–449, 2005; Arch Dis Child 60:763–766, 1985; JAMA 157:651–652, 1955 Malnutrition or starvation - hypertrichosis; trichomegaly Ped Derm 18:57–59, 2001; Acta Paediatr Scand 40:59–69, 1951 Porphyria – porphyria cutanea tarda Rook p. 2590, 1998, Sixth Edition; congenital erythropoietic porphyria – blisters, scarring, hyperpigmentation, mutilating ulcers, hypertrichosis, erythrodontia, corneal scarring, keratoconjunctivitis, cataracts; uroporphyrinogen III synthase deficiency Ped Derm 36:951–952, 2019; JAAD 67:1093–1110, 2012; AD 141: 1575–1579, 2005; Ped Derm 20:498–501, 2003; adult onset congenital erythropoietic porphyria with myelodysplasia syndrome AD 145:948–949, 2009; harderoporphyria, hepatoerythropoietic porphyria - blisters and prominent hypertrichosis - uroporphyrinogen decarboxylase deficiency(8–18% of normal values); differential diagnosis includes infantile PCT(clinically indistinguishable), erythropoietic protoporphyria(no hypertrichosis or bullae), and Gunther's disease(severe mutilation, erythrodontia, splenomegaly and hemolytic anemia) Ped Derm 4:229–233, 1987; variegate porphyria JAAD 2:36–43, 1980; hereditary coproporphyria BJD 96:549–554, 1977; Q J Med 46:229–241, 1977; BJD 84:301–310, 1971; hepatoerythropoietic porphyria – extreme photosensitivity, skin fragility in sun-exposed areas, hypertrichosis, erythrodontia, pink urine, sclerodermoid changes AD 146:529–533, 2010 Starvation Stein-Leventhal syndrome – polycystic ovarian disease

NEOPLASTIC DISORDERS Epidermal nevus - secreting LHRH - hirsutism Melanocytic nevus - giant congenital melanocytic nevus Ped Derm 18:369–377, 2001

Prepubertal hypertrichosis – widespread diffuse involvement becomes obvious during childhood; forehead, temples, preauricular areas, proximal extensor back; inverted fir tree pattern; thick bushy eyebrows, low set anterior hairline Primary generalized hypertrichosis(hypertrichosis lanuginosa congenita, congenital generalized hypertrichosis, universal hypertrichosis) Ped Derm 31:529–530, 2014; AD 137:877–884, 2001; Clin Genet 10:303–306, 1976

PSYCHOCUTANEOUS DISORDERS Eating disorders – anorexia nervosa, bulemia nervosa - increased lanugo body hair – fine downy hair of abdomen, back, and forearms Am J Clin Dermatol 6:165–173, 2005; Ped Derm 18:57–59, 2001; Int J Derm 39:348–353, 2000; Ped Derm 16:90–94, 1999 Schizophrenia

SYNDROMES Acromegaloid facial appearance and generalized hypertrichosis J Med Genet 33:972–974, 1996 Acroosteolysis(Hajdu-Cheney syndrome) Birth Defects 10:106–123, 1974 Ambras syndrome – hypertrichosis universalis congenital; fine silky light colored hair primarily of face, ears, shoulders, nose; associated minor facial dysmorphism, supernumerary nipples, dental anomalies Clin Genet 44:121–128, 1993 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies(bilateral ablepharon, ectropion of lower eyelids, hypertelorism, long wide mouth(macrostomia), anteriorly folded ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Am J Med Genet 86:54–56, 1999; Am J Med Genet 73:366–367, 1997; Am J Med Genet 47:20–23, 1993; Syndrome Ident 8:6–9, 1982 Berardinelli’s(Berardinelli-Seip) syndrome – lipodystrophy with muscular hypertrophy; coarse hypertrichotic skin J Clin Endocrinol Metab 14:193–204, 1954

Hypertrichosis, Generalized Cantu syndrome – congenital hypertrichosis, cardiomegaly, osteochondrodysplasia, coarse acromegalic facial features, deep plantar creases; mutation in ABCC9 Appl Clin Genet 17:15–21, 2018; Am J Med 92:191–194, 2000; Am J Med Genet 94:421–427, 2000; Am J Med Genet 69:138–151, 1997 Cataract, hypertrichosis, and mental retardation – autosomal recessive Am J Med Genet 41:432–433, 1991 Cerebral malformation, seizures, hypertrichosis, distinct face, claw hands, and overlapping fingers Am J Med Genet 47:698–701, 1993

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thia with increased jowls and prominent puffy eyelids, shortened extremities, prominent visible vasculature, ecchymoses, excessive skin folds, blue sclerae, umbilical hernia, hyperconvex nails, delayed closure of fontanelles AD 129:1310–1315, 1993 Donahue syndrome(leprechaunism) – - extensive hypertrichosis, congenital insulin resistance; dwarfism; elfin-like face, large eyes, thick lips, low set ears, less subcutaneous fat, excessive folding of skin; mental retardation Acta Paediatr 83:18, 1994; AD 117:531– 535, 1981

Coffin-Siris syndrome - hypertrichosis of the face and body, bushy eyebrows, lumbosacral hirsutism; coarse facial features, low birthweight, retarded growth, mental retardation, hypoplastic or absent fifth fingernails and toenails J Med Genet 27:333–336, 1990; Am J Dis Child 132:1044, 1978

Dup(3q) syndrome Acta Paediatr Scand 73:281–284, 1984

Cone-rod congenital amaurosis associated with congenital hypertrichosis J Med Genet 26:504–510, 1989

Fetal hydantoin syndrome - hypertrichosis, broad depressed nasal bridge, large lips, wide mouth, short webbed neck, short stature, hypoplastic distal phalanges JAAD 48:161–179, 2003; JAAD 46:161–183, 2002

Congenital cataracts, sensorineural deafness, hypogonadism, hypertrichosis, short stature Clin Dysmorphol 4:283–288, 1995 Congenital diffuse lipomatosis (Michelin tire baby) – nevus lipomatosis superficialis or smooth muscle hamartoma, symmetric ringed creases of extremities with hirsutism of arms, legs, shoulders, buttocks Cornelia de Lange(Brachmann-de Lange) syndrome – generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, posterior neck, and arms, low set ears, arched palate, antimongoloid palpebrae; congenital eyelashes Ped Derm 24:421– 423, 2007; JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993 Costello syndrome - generalized hypertrichosis; warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet; acanthosis nigricans; low set protuberant ears, thick palmoplantar surfaces with single palmar crease, gingival hyperplasia, hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, multiple nevi Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Aust Paediat J 13:114–118, 1977 Craniodysostosis with extremity bands Craniofacial dysostosis and patent ductus arteriosus - severe hypertrichosis of extremities and back, multiple defects of eyes and teeth, ocular and cardiac defects, hypoplasia of labia majora J Paediatr 56:778–785, 1960 CRIE syndrome - congenital reticulated ichthyosiform erythroderma Dermatology 188:40–45, 1994 Cytochrome c Oxidase-Deficient Leigh Syndrome Mol Genet Metab 73:34–343, 2001 Depigmented hypertrichosis with dilated follicular pores, short stature, scoliosis, short broad feet, macrocephaly, dysmorphic facies, supernumerary nipple, and mental retardation(cerebralocular malformations) BJD 142:1204–1207, 2000 Dermatospiraxis(Ehlers Danlos type VII-C)-facial vellus hairs - autosomal recessive; lack of Type 1 procollagen N-proteinase; irregular circular collagen fibres on electron microscopy; premature rupture of membranes; extreme skin fragility and laxity; vellus hairs, microgna-

Familial hypertrichosis lanuginose AD 147:746–747, 2011 Fetal alcohol syndrome - hypertrichosis, small face, capillary hemangiomas, physical and mental retardation JAAD 48:161–179, 2003; JAAD 46:161–183, 2002; JAMA 235:1458–1460, 1976

Gingival fibromatosis and hypertrichosis syndrome - hypertrichosis of face, trunk, and eyebrows, mental retardation and seizures(resembles diphenylhydantoin syndrome) AD 137:877–884, 2001; J Oral Maxillofacial Surg 46:415–420, 1988; J Pediatr 67:499–502, 1965 Gingival fibromatosis-hypertrichosis syndrome(Byars-Jurkiewicz syndrome) - fibroadenomas of breast J Pediatr 67:499–502, 1965 Goltz’s syndrome AD 137:1095–1100, 2001 Gorlin-Chaudhry-Moss syndrome – short and stocky with craniosynostosis, midface hypoplasia, hypertrichosis of the scalp, arms, legs, and back, anomalies of the eyes, digits, teeth, and heart, and genitalia hypoplasia Am J Med Genet 44:518–522, 1992 H syndrome(low height, heart, hallus valgus, hormonal, hypogonadism, hematologic) – sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; starts on feet and legs and progresses upward; hypertrichosis, short stature, facial telangiectasia, ichthyosiform changes, gynecomastia, varicose veins, skeletal deformities(camptodactyly of 5th fingers), scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, micropenis, azospermia, sensorineural hearing loss, dilated scleral vessels, exophthalmos, cardiac anomalies, hepatosplenomegaly, mental retardation; mutation in nucleoside transporter Hent3 JAAD 70:80–88, 2014; BJD 162:1132–1134, 2010; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008 Hammerschlag-Telfer syndrome Hemihyperplasia Syndromes of the Head and Neck, p. 329, 1990 Hunter’s syndrome (mucopolysaccharidosis type II) – fleshy ivory white papules and nodules(pebbling) in ridging or reticular pattern, symmetric, involving area between the angle of the scapula and anterior axillary line; coarse facial features, luxuriant scalp hair; bony abnormalities, recurrent umbilical and inguinal hernias; recurrent otitis media and pneumonia; developmental delay; coarse straight scalp hair; hypertrichosis of body and face; slate grey nevi; bilateral knee pain; decreased sulfoiduronate sulfatase (L-iduronate2-sulfatase) resulting in buildup of dermatan sulfate and heparin sulfate Ped Derm 37:369–370, 2020; Ped Derm 15:370–373, 1998 Hurler’s syndrome - personal observation Hyperostotic internal craniopathy(Morgani’s syndrome) Hypertrichosis, coarse face, brachydactyly, obesity, mental retardation, broad proximal phalanges, small dysmorphic nails Clin Dysmorphol 5:223–229, 1996 Hypertrichosis osteochondrodysplasia Hum Genet 60:36–41, 1982

522 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Hypertrichosis, pigmentary retinopathy, and facial anomalies Am J Med Genet 62:386–390, 1996 Hypomelanosis of Ito Indian Dermatol Online J 10:316–318, 2019 Insulin-resistant diabetes mellitus with acanthosis nigricans and hypertension – autosomal recessive; severe hyperinsulinemia, amenorrhea, hirsutism; mutation in muscle-specific regulatory subunit of protein phosphatase 1(PPAR-gamma and PP1R3A) BJD 147:1096–1011, 2002 Julia Pastrana syndrome – congenital generalized hypertrichosis terminali – facial deformities and gingival hyperplasia Am J Med Genet 47:198–212, 1993 Krabbe’s disease(globoid leukodystrophy) AD 111:230–236, 1975 Laband syndrome(Zimmermann-Laband syndrome) – autosomal dominant; hypertrichosis, gingival hypertrophy; aplasia or dysplasia of fingernails and distal phalanges, hypertrophy of nasal tip and ears, hypermobility, limb asymmetry, intellectual disability Am J Med Genet 31:691–695, 1988 Lawrence-Seip syndrome(congenital generalized lipodystrophy) lipoatrophic diabetes – generalized hypertrichosis with luxuriant scalp hair AD 91:326–334, 1965 Macrostomia, ectropion, atrophic skin, hypertrichosis, and growth retardation Marshall-Smith syndrome Am J Med Genet 20:559–562, 1985

Rabson-Mendenhall syndrome(pineal hyperplasia syndrome - autosomal recessive, pineal hyperplasia, insulin-resistant diabetes mellitus, unusual coarse facies, dental precocity, hypertrichosis, acanthosis nigricans, and premature sexual development Ramon syndrome - cherubism, gingival fibromatosis, epilepsy, cherubism, mental and somatic retardation, hypertrichosis, and stunted growth Develop Med Child Neurol 31:538–542, 1989; Am J Med Genet 25:433–442, 1986 Rubinstein-Taybi syndrome(broad thumb - hallux syndrome) hypertrichosis of trunk, limbs, and face Ped Derm 11:21–25, 1994 Schinzel-Giedion syndrome - autosomal recessive - ectodermal dysplasia; midface retraction, hirsutism, telangiectasias of nose and cheeks, skeletal anomalies, mental retardation Hum Genet 62:382, 1982; Am J Med Genet 1:361–375, 1978 Scott syndrome(craniodigital syndrome) J Pediatr 78:658–663, 1971 Seckel syndrome(bird-headed dwarfism) Am J Med Genet 12:7–21, 1982 Short stature, mental retardation, ocular abnormalities – hypertrichosis Helv Paediat Acta 27:463–469, 1972 Stiff skin syndrome – sclerodermoid changes of pelvic or shoulder girdle, limited joint mobility, mild overlying hypertrichosis, especially over lumbosacral area; or generalized hypertrichosis JAAD 75:163–168, 2016; AD 144:1351–1359, 2008

MELAS syndrome – mitochondrial encephalopathy with lactic acidosis and strokelike episodes JAAD 41:469–473, 1999

Trisomy 18

Melnick-Needles syndrome J Pediatr Orthoped 3:387–391, 1983

Wiedemann-Steiner syndrome – hypertrichosis, prominent forehead, low hairline, small ears, hypertelorism, bushy eyebrows, localized thickened cutaneous plaques; dwarfism, peripheral corneal opacities, coarse facial features

Michelin tire baby syndrome - smooth muscle hamartomas or increase in fat JAAD 28:364–370, 1992; Ped Derm 6:329–331, 1989 Mitochondrial respiratory chain disorders Pediatrics 103:428–433, 1999 Morquio's syndrome - mucopolysaccharidosis with bone changes, hypertrichosis and corneal opacities Mucolipidoses(pseudo-Hurler polydystrophy) BJD 130:528–533, 1994 Mucopolysaccharidoses(Hurler’s, Hurler-Schei, Sanfilippo, Morquio, Maroteaux-Lamy, Sly syndromes) – coarse facies; Hunter's syndrome NEJM 284:221–222, 1971; Hurler’s syndrome – face, trunk, and extremities; bushy eyebrows with synophrys NEJM 284:221–222, 1971; Schei syndrome Syndromes of the Head and Neck, p. 104–105, 1990 Noonan's syndrome Am J Dis Child 116:359–366, 1968 Osteochondrodysplasia with hypertrichosis Hum Genet 60:36–41, 1982 Parana hard skin syndrome(stiff skin syndrome)(congenital fascial dystrophy – hirsutism, stiff skin, knuckle pad-like thickening of fingers, limited joint mobility, localized areas of stony hard skin of buttocks and legs Ped Derm 20:339–341, 2003; Ped Derm 19:67–72, 2002; JAAD 21:943–950, 1989; Ped Derm 3:48–53, 1985; Ped Derm 2:87–97, 1984 Patterson-David syndrome – redundant skin, hypertrichosis Birth Defects 5:117–121, 1969 POEMS syndrome(Crow-Fukase syndrome)(osteosclerotic myeloma) - polyneuropathy, organomegaly, endocrinopathies, lambda light chain M-spike, skin changes including hyperpigmentation, sclerodermatous thickening, hirsutism, hypertrichosis, angiomas Blood Reviews 21:285–299, 2007; JAAD 55:149–152, 2006; JAAD 40:507–535, 1999; JAAD 40:808–812, 1999; Cutis 61:329–334, 1998; AD 124:695–698, 1988; Nippon Shinson 26:2444–2456, 1968

Waardenburg syndrome

Winchester syndrome – annular and serpiginous thickenings of skin; arthropathy, gargoyle-like face, gingival hypertrophy, macroglossia, osteolysis(multilayered symmetric restrictive banding), generalized hypertrichosis, very short stature, thickening and stiffness of skin with annular and serpiginous thickenings of skin, multiple subcutaneous nodules JAAD 55:1036–1043, 2006; JAAD 50:S53–56, 2004; AD 111:23–236, 1975 X-linked dominant hypertrichosis Hum Genet 66:66–70, 1984

TOXINS Acrodynia – face, trunk, limbs Ped Derm 18:57–59, 2001; Acta Paediatr Scand 40:59–69, 1951 Hexachlorobenzene Toxic oil syndrome(chronic phase) JAAD 18:313–324, 1988

TRAUMA S/P head injuries S/P traumatic shock AD 71:401–402, 1955

HYPERTRICHOSIS, LOCALIZED  UTOIMMUNE AND DISORDERS OF IMMUNE A DYSREGULATION Allergic contact dermatitis to aluminum in pneumococcal vaccine – hypertrichotic nodule Ped Derm 36:145–146, 2019

Hypertrichosis, Localized

CONGENITAL AND INHERITED DISORDERS Aarskog syndrome – widow’s peak J Pediatr 77:856–861, 1970 Ablepharon with follicular ichthyosis and hairy pinnae Clin Genet 2:111–114, 1971 Accessory tragus – vellus hairs on the surface; ear papule - isolated, Treacher Collins syndrome(mandibulofacial dysostosis; autosomal dominant), Goldenhaar syndrome((oculo-auriculo-vertebral syndrome) - macroglossia, preauricular tags, abnormal pinnae, facial asymmetry, macrostomia, epibulbar dermoids, facial weakness, central nervous system, renal, and skeletal anomalies), Nagers syndrome, Wolf-­Hirschhorn syndrome(chromosome 4 deletion syndrome), oculocerebrocutaneous syndrome Ped Derm 17:391– 394, 2000; Townes-Brocks syndrome Am J Med Genet 18:147–152, 1984; VACTERL syndrome J Pediatr 93:270–273, 1978 Acrofrontofacionasal dysostosis - widow’s peak Am J Med Genet 20:631–638, 1985 Ambras syndrome – facial hypertrichosis of forehead, cheeks, preauricular region, nose Clin Genet 57:157–158, 2000 Angora hair nevus – linear epidermal nevus covered with long soft white hair(Schauder syndrome) Adv Dermatol 18:175–201, 2002; BJD 142:1204–1207, 2000 Anterior cervical hypertrichosis – autosomal dominant; present from birth to early childhood; Ped Derm 35:669–670, 2018; Ped Derm 32:252–255, 2015; Ped Derm 27:530–531, 2010; JAAD 48:161–179, 2003; AD 137:877–884, 2001; Am J Med Genet 55:498–499, 1995; familial JAAD 53:530–531, 2005; associated with sensory and motor neuropathy, mental retardation JAAD 25:767–770, 1991 Aplasia cutis congenita; hair collar sign and vascular stain Ped Derm 22:200–205, 2005 Ataxia telangiectasia(Louis-Bar disease)- hirsutism; autosomal recessive; oculocutaneous telangiectasias with cerebellar ataxia, choreoathetosis, and recurrent pulmonary infections; low IgA; skin may become sclerodermoid; high alpha fetoprotein and carcinoembryonic antigen; defects in DNA repair; 11q22–23; solid tumors and lymphoreticular malignancies are associated Ped Derm 28:494–501, 2011; JAAD 10:431–438, 1984; telangiectasias of face, ocular telangiectasia, extensor surfaces of arms and bulbar conjunctiva; café au lait macules, hypopigmented macules, melanocytic nevi, facial papulosquamous rash, hypertrichosis, bird-like facies; immunodeficiency, increased risk of leukemia, lymphoma; cerebellar ataxia with eye movement signs, mental retardation, and other neurologic defects; cafe au lait macules JAAD 68:932–936, 2013; Ann Int Med 99:367–379, 1983 Atretic encephalocoele Atretic meningocoele Bald cyst with surrounding hypertrichosis("hair collar sign") AD 125:1253–1256, 1989   Aplasia cutis congenita, membranous AD 137:45–50, 2001   Atretic encephalocoele   Atretic meningocoele   Cutaneous meningioma(psammoma)   Encephalocoele AD 137:45–50, 2001   Herniated brain tissue with connection to brain; associated with local defect in cranial bones.   Heterotopic brain tissue - bald cyst of scalp with surrounding hypertrichosis; extracranial brain tissue; presents in neonates as circular bald lesions 2–4 cm on scalp; cystic or solid, red-blue; occur on occiput; needs to be differentiated from neurofibroma, porokeratosis of Mibelli, triangular alopecia, epithelial nevi and tumors, vascular nevi(including lymphangioma), and cephalohematoma, and other lesions

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associated with localized hypertrichosis AD 137:45–50, 2001; BJD 129:183–185, 1993; AD 125:1253–1256, 1989    Intracranial dermal sinus tract    Oculocerebral cutaneous syndrome    Pre-auricular skin defects AD 133:1551–1554, 1997   Rudimentary meningocoele and membranous aplasia cutis congenita AD 137:45–50, 2001; AD 131:1427–1431, 1995   Subcutaneous meningocoele Barber-Say syndrome - hypertrichosis of back and neck, eyebrows, eyelashes, large mouth, abnormal external ears, wrinkled, lax, atrophic skin JAAD 48:161–179, 2003 Becker’s nevus NEJM 372:1249, 2015; JAAD 48:161–179, 2003; Arch Dermatol Syphilol 60:155–160, 1949; congenital Ped Derm 14:373–375, 1997 Benign fibrous tumor – hair collar sign and vascular stain Ped Derm 22:200–205, 2005 Berardinelli-Seip syndrome – autosomal recessive; lipoatrophic diabetes mellitus JAAD 48:161–179, 2003 Brachycephalofrontonasal dysplasia - widow’s peak Am J Med Genet 28:581–591, 1987 Cantu syndrome – osteochondrodysplasia with hypertrichosis – autosomal recessive, autosomal dominant JAAD 48:161–179, 2003 Centrofacial lentiginosis – synophrys, high arched palate, sacral hypertrichosis, spina bifida, scoliosis BJD 94:39–43, 1976 Cephalocele – includes meningocele(rudimentary meningocele), meningoencephalocele, meningomyelocele; blue nodule with overlying hypertrichosis JAAD 46:934–941, 2002; AD 137:45–50, 2001 Cone-rod congenital amaurosis associated with congenital hypertrichosis J Med Genet 26:504–510, 1989 Coffin-Siris syndrome – autosomal recessive; hypertrichosis of eyelashes, eyebrows, and lumbosacral areas JAAD 48:161–179, 2003 Congenital adrenal hyperplasia – hirsutism Congenital erythropoietic porphyria – gingival recession; bullous photosensitivity, photomutilation, fixed flexion deformities, resorption of fingertips, blepharitis, ectropion, meibomian cysts, conjunctivitis, loss of eyebrows, erythrodontia(purple teeth), dental caries, overcrowding of teeth, facial hypertrichosis, scarring alopecia due to recurrent blistering, dyschromatosis; neonatal jaundice, hemolytic anemia, splenomegaly due to pancytopenia BJD 171:422–423, 2014; BJD 167:988–900, 2012 Congenital hairy elbows(hypertrichosis cubiti) Cutis 36:69–85, Congenital hairy malformation of the palms and soles AD 111:1146–1149, 1975 Congenital hypertrichosis lanuginosa – autosomal dominant JAAD 48:161–179, 2003; J Genet Human 17:10–13, 1969 Congenital hypertrichosis lanuginosa and dental anomalies Clin Genet 10:303–306, 1976 Congenital hypertrichotic melanoneurocytoma – congenital hypertrichotic hyperpigmented plaque JAAD 67:799–801, 2012 Congenital macrogingivae Congenital melanocytic nevus Congenital melanosis and hyperpigmentation Ped Derm 15:290– 292, 1998 Congenital smooth muscle hamartoma JAAD 48:161–179, 2003; JAAD 46:477–490, 2002; Curr Prob Derm 14:41–70, 2002; Ped Derm 13:431–433, 1996; AD 125:820–822, 1989; AD 121:1200– 1201, 1985; AD 114:104–106, 1978

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Cornelia de Lange(Brachmann-de Lange) syndrome – specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, synophrys; long delicate eyelashes, cutis marmorata, skin around eyes and nose with bluish tinge, red nose Ped Derm 19:42–45, 2002; JAAD 37:295–297, 1997; J Pediatr Ophthalmol Strabismus 27:94–102, 1990

Erythrokeratoderma variabilis

Costello syndrome – thick eyebrows, verrucous papillomas of nose and arms; growth and mental retardation, sociable, depressed nasal bridge, low set ears with thick earlobes, short neck, limited joint mobility, cardiac abnormalities, malignancies(rhabdomyosarcoma, ganglioneuroblastoma, neuroblastoma, bladder carcinoma), loose redundant skin of neck, hands and feet with deep creases of palms and soles, acanthosis nigricans, pigmented acral nevi, vascular birthmarks, hyperkeratosis, hyperpigmentation of skin, thin nails, sparse curly scalp hair; mutation in HRAS gene Am J Med Genet 117:42–48, 2003

Familial congenital anterior cervical hypertrichosis associated with peripheral sensory and motor neuropathy J Pediatr Ophthalmol Strabismus 34:309–312, 1997

Craniofacial dysostosis JAAD 48:161–179, 2003

Fetal alcohol syndrome JAAD 48:161–179, 2003

Craniofrontonasal dysplasia - widow’s peak Birth Defects 15:85–89, 1979 Cretinism – coarse facial features, lethargy, macroglossia, cold dry skin, livedo, umbilical hernia, poor muscle tone, coarse scalp hair, synophrys, no pubic or axillary hair at puberty Cutaneous heterotopic meningeal nodule - Type I cutaneous meningioma Depigmented hypertrichosis with dilated follicular orifices following Blaschko’s lines associated with cerebral and ocular malformations BJD 142:1204–1207, 2000 Dermal dendrocyte hamartoma – pedunculated red nodule with stubby white hair JAAD 32:318–321, 1995 Dermatofibrosarcoma protuberans – congenital; hair collar sign AD 139:207–211, 2003 Dermoid cyst – central tuft of hair; nasal dermoid sinus cyst – pit of central nose with wisps of terminal hair Ped Derm 24:646–650, 2007 Distichiasis(double row of eyelashes) – autosomal dominant J Med Genet 13:514–515, 1976 Distichiasis and congenital anomalies of the heart and peripheral vasculature Am J Med Genet 20:283–294, 1985 Distichiasis-lymphedema syndrome - double row of eyelashes BJD 142:148–152, 2000; AD 135:347–348, 1999; Hum Genet 53:309– 310, 1980 Donohue syndrome(leprechaunism) - forehead and cheeks JAAD 48:161–179, 2003 dup(3q) syndrome – synophrys Birth Defects 14:191–217, 1978 Duplication of eyebrows, stretchable skin and syndactyly Eccrine angiomatous hamartoma – vascular nodule; macule, red plaque, acral nodule of infants or neonates; painful, red, purple, blue, blue-­brown, yellow, brown, skin-colored plaque or macule JAAD 51:301–304, 2004; Cutis 71:449–455, 2003; JAAD 47:429– 435, 2002; JAAD 37:523–549, 1997; Ped Derm 13:139–142, 1996; Virchow Arch Pathol Anat 16:160, 1859 Ectopic meningeal tissue – hair collar sign Ped Derm 24:657–658, 2007 Edward's syndrome(Trisomy 18) - hypertrichosis of forehead Encephalocoele – anterior encephalocele – facial nodule JAAD 51:577–579, 2004 Epidermal nevus, linear Epidermolysis bullosa, dystrophic – face and extremities

Erythropoietic porphyria Erythropoietic protoporphyria Familial cervical hypertrichosis with underlying kyphoscoliosis JAAD 20:1069–1072, 1989

Familial X/Y translocation Clin Genet 24:380–383, 1983 Faun tail nevus with underlying spinal dysraphism; meningocele, diastematomyelia, spina bifida, kyphoscoliosis, scoliosis, chest deformities (primary faun tail deformity)(lumbosacral hypertrichosis) (spina bifida occulta) NEJM 370:466, 2014; Ped Derm 26:484–485, 2009; BJD 156:1065–1066, 2007; Curr Prob in Dermatol 13:249– 300, 2002; AD 137:877–884, 2001 Fetal folate antagonists syndrome(methotrexate) - widow’s peak J Pediatr 72:790–795, 1968 Fetal hydantoin syndrome JAAD 48:161–179, 2003 Fetal trimethadione syndrome – synophrys Teratology 3:349–362, 1970 FG syndrome - widow’s peak Am J Med Genet 19:383–386, 1984 Fibrous hamartoma of infancy - hairy plaque on arm; skin colored plaque with hypertrichosis and hyperhidrosis Ped Derm 32:533– 535, 2015; JAAD 41:857–859, 1999; hypertrichotic pink nodule of back BJD 156:1052–1055, 2007; dimpled subcutaneous mass with hypertrichosis; bony remodeling and muscle atrophy Ped Derm 36:677–680, 2019 Focal facial dermal dysplasia without other facial anomalies – autosomal dominant; oval symmetrical scarred areas on temples, cheeks, rim of fine lanugo hairs BJD 84:410–416, 1971 Fronto-facio-nasal dysplasia - widow’s peak Am J Med Genet 10:409–412, 1981 Frontometaphyseal dysplasia – hypertrichosis of buttocks and thighs Radiol Clin N Am 10:225243, 1972 Fucosidosis Gingival fibromatosis, hypertrichosis, cherubism, mental and somatic retardation, and epilepsy(Ramon syndrome) Am J Med Genet 25:433–442, 1986 Gingival fibromatosis-hypertrichosis syndrome(Byars-Jurkiewicz syndrome) – autosomal dominant, autosomal recessive; giant fibroadenomas of breast; hypertrichosis of face, upper extremities, midback; secondary kyphosis, hypertrichosis, gingival fibromatosis JAAD 48:161–179, 2003; Ped Derm 18:534–536, 2001; J Pediatr 67:499–502, 1965; Plast Reconstr Surg 27:608–612, 1961 Gingival fibromatosis with distinctive facies – autosomal recessive; macrocephaly, hypertelorism, bushy eyebrows, synophrys, downslanted palpebral fissures, flat nasal bridge with hypoplastic nares, cupid-bow mouth, high arched palate Ped Derm 18:534–536, 2001 H syndrome – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; mutation in SLC29A3 gene(equilabrative nucleoside transporter) Ped Derm 33:602–614, 2016

Hypertrichosis, Localized Hair collar sign – as sign of spinal neural tube defects Am J Med Genet 146:484–487, 2008; Ped Derm 24:138–140, 2007; Clin Exp Dermatol 30:497–499, 2005; Pediatrics 96:309–313, 1995; AD 125:1253–1256, 1989; cranial bone defects with direct communication with the central nervous system; venous malformations; combined nevus; meningeal heterotopia, sinus pericranii, paraganglioma JAAD 76:478–487, 2017; with protruding scalp mass – aplasia cutis with sinus pericranii; irregular plaque of aplasia with yellow crusts and prominent blood vessels Ped Derm 37:40–51, 2020 Hair collar sign and vascular stain – benign fibrous tumor, meningothelial hamartoma, aplasia cutis congenita Ped Derm 22:200–205, 2005; encephalocele, meningocele, membranous aplasia cutis congenita, heterotopic brain tissue, ectopic meningeal tissue Ped Derm 24:657–658, 2007; Dermatol Therapy 18:104–116, 2005; sinus pericranii – communication of extracranial veins with intracranial venous system – hair collar sign Ped Derm 31:397–399, 2014 Hairy cutaneous malformation of the palms and soles (familial hypertrichosis of the palms and soles JAAD 48:161–179, 2003; AD 111:1146–1149, 1975 Hajdu-Cheney syndrome(osteolysis) - broad eyebrows(synophrys) J Periodontol 55:224–229, 1984

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palmoplantar kertoderma; loss of dermatoglyphics; temporary hypertrichosis of normal skin BJD 166:434–439, 2012; JAAD 63:607–641, 2010 IL 10R deficiency – hypertrichosis of forehead and back BJD 178:335–349, 2018 Kabuki makeup syndrome – long eyelashes J Pediatr 105:849–850, 1984 Mal de Meleda – autosomal dominant, autosomal recessive transgrediens with acral erythema in glove-like distribution; hairy palms and soles Dermatology 203:7–13, 2001; AD 136:1247–1252, 2000; J Dermatol 27:664–668, 2000; Dermatologica 171:30–37, 1985 Mandibulofacial dysostosis - distichiasis Mannosidosis – autosomal recessive; gingival hypertrophy, macroglossia, coarse features, prognathism, thick eyebrows, low anterior hairline, deafness, lens opacities, hepatosplenomegaly, recurrent respiratory tract infections, muscular hypotonia, mental retardation Ped Derm 18:534–536, 2001 Medallion-like dermal dendrocyte hamartoma – blue-brown oval depression of back of neonate; thin hair on surface AD 142:921– 926, 2006

Happle-Tinschert syndrome – segmental basaloid follicular hamartomas; ipsilateral hypertrichosis; hypo- and hyperpigmentation; linear atrophoderma; osseous, dental, and/or cerebral defects BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221–225, 2009; Acta DV 88:382–387, 2008

Melanocytic nevus, congenital BJD 164:1037–1042, 2011; JAAD 48:161–179, 2003; JAAD 36:409–416, 1997

Hemihypertrophy with hypertrichosis JAAD 48:161–179, 2003

JAAD 41:469–473, 1999

Hemimaxillofacial dysplasia(segmental odontomaxillary dysplasia) (HATS – hemimaxillary enlargement, asymmetry of face, skin findings)– facial asymmetry, hypertrichosis of the face, unilateral maxillary enlargement, partial anodontia, delayed eruption of teeth, gingival thickening of affected segment, Becker’s nevus, hairy nevus(hypertrichosis), lip hypopigmentation, depression of cheek, erythema, hypoplastic teeth Ped Derm 21:448–451, 2004; JAAD 48:161–179, 2003; Oral Surg Oral Med Oral Pathol 64:445–448, 1987 Hermansky-Pudlak syndrome - hypertrichosis of the eyebrows, and trichomegaly of the arms and legs AD 135:774–780, 1999 Heterotopic brain tissue Heterotopic meningeal tissue – hypertrichosis covering entire lesion BJD 156:1047–1050, 2007; AD 130:775–777, 1994; JAAD 30:363–366, 1994 Hirsutism Hunter’s syndrome JAAD 48:161–179, 2003 Hurler’s syndrome JAAD 48:161–179, 2003 Hypertrichosis cubiti(hairy elbow) JAAD 48:161–179, 2003; AD 137:877–884, 2001; Clin Exp Dermatol 24:497–498, 1999 Hypertrichosis, pigmentary retinopathy, and facial anomalies – lipoatrophy of buttocks Am J Med Genet 62:386–390, 1996 Hypertrichosis pinnae in babies of diabetic mothers JAAD 48:161–179, 2003; Indian Pediatr 24:87–89, 1987; Pediatr 68:745–6, 1981 Hypertrichosis of eyebrows and nasal tip of adolescence Hypomelanosis of Ito – focal hypertrichosis JAAD 48:161–179, 2003; Dermatology 193:63–64, 1996; of genital area or back Ped Derm 19:536–540, 2002 Ichthyosis en confetti(congenital reticulated ichthyosiform erythroderma) – reticulated erythroderma with guttate hypopigmentation,

Melanoma JAAD 56:413–416, 2007; Rocky Mt Med J 51:280–282, 1954 MELAS syndrome - mitochondrial encephalomyopathy with lactic acidosis - hypertrichosis of the legs JAAD 48:161–179, 2003; Meningeal heterotopia(ectopic rests of meningeal tissue that have lost central nervous system connection) and rudimentary or atretic meningoceles – exophytic nodular or cystic mass of occipital or parietal scalp – normal skin; glistening or bullous appearance, alopecia, hair collar Ped Derm 32:161–170, 2015 Meningioma - nodule with overlying alopecia or hypertrichosis JAAD 46:934–941, 2002; Eur J Pediatr Surg 10:387–389, 2000; primary cutaneous meningioma, including rudimentary meningocele with tuft of hair over vertebral column J Neurosurg 60:1097–1098, 1984; AD 130:775–777, 1994; JAAD 30:363–366, 1994 Meningocoele, cranial Meningothelial hamartoma – hair collar sign and vascular stain Ped Derm 22:200–205, 2005 Mitochondrial disorders – hypertrichosis of the back or diffusely on the back, forearms, and forehead; erythematous photodistributed eruptions followed by mottled or reticulated hyperpigmentation; alopecia with or without hair shaft abnormalities including trichothiodystrophy, trichoschisis, tiger tail pattern, pili torti, longitudinal grooving, and trichorhexis nodosa Pediatrics 103:428–433, 1999 Mucopolysaccharidoses types I, II, III, IV, VI - thick eyebrows with synophrys JAAD 37:295–297, 1997; Sanfilippo syndrome(mucopolysaccharidosis III) JAAD 48:161–179, 2003; Dur J Pediatr 130:251–258, 1979 Mucopolysaccharidosis type IX – autosomal recessive; hyaluronidase 1 deficiency; soft tissue masses, short stature, coarse facies, hypertrichosis, synophrys; accumulation of hyaluronic acid Ped Derm 33:594–601, 2016 Neurofibromatosis – plexiform neurofibroma Curr Prob in Dermatol 13:249–300, 2002 Neurofibroma JAAD 48:161–179, 2003; pigmented plexiform neurofibroma JAAD 56:862–868, 2007; Ann DV 128:619–621, 2001

526 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Nevoid hypertrichosis JAAD 48:161–179, 2003; JAAD 39:114–115, 1998; Am J Med Genet 79:195–196, 1998; Clin Exp Dermatol 16:74, 1991; multiple nevoid hypertrichosis Ped Derm 26:436–438, 2009 Nevus lipomatosis superficialis Int J Dermatol 41:241–243, 2002; BJD 87:557–564, 1972 Noonan's syndrome - downy hypertrichosis on cheeks and shoulders AD 114:929–930, 1978 Occult spinal dysraphism – faun tail nevus; dermoid cyst or sinus, myelomeninocele, diastematomyelia, vertebral abnormalities, subdural or extradural lipoma, meningioma JAAD 48:161–179, 2003; Ped Clin North Am 47:813–823, 2000 Oliver-McFarlane syndrome - trichomegaly with mental retardation, dwarfism, and pigmentary degeneration of the retina Ped Derm 29:234–235, 2012; Br J Ophthalmol 87_119–120, 2003; JAAD 37:295–297, 1997; Can J Ophthalmol 28:191–193, 1993 Opitz trigonocephaly syndrome - hypertrichosis of forehead; widow’s peak Am J Dis Child 129:1348, 1975

Posterior cervical hypertrichosis – present at birth; associated with kyphoscoliosis Primary multifocal hypertrichosis Eur J Dermatol 11:35–37, 2001 Proteus syndrome AD 140:947–953, 2004 Rubinstein-Taybi syndrome(broad thumb hallux syndrome) – chromosome 16p; mutation in gene encoding cyclic adenosine monophosphate response element-binding protein Nature 376:348– 351, 1995; mental deficiency, small head, broad thumbs and great toes, beaked nose, malformed low-set ears, capillary nevus of forehead, hypertrichosis of back, shoulders, and eyebrows, synophrys, keloids, cardiac defects JAAD 56:541–564, 2007; JAAD 48:161–179, 2003; JAAD 46:161–183, 2002; JAAD 37:295–297, 1997; Cutis 57:346–348, 1996; Am J Dis Child 105:588–608, 1963; hirsutism of shoulders and back Am J Med Genet Suppl 6:17–29, 1990 Rudimentary meningocoele and membranous aplasia cutis AD 131:1427–31, 1995

Oral hair Oral Surg 49:530–531, 1980

Sequestrated meningocoele - either tuft of hair or annular array of hair Ped Derm 14:315–318, 1994

Penchaszadeh syndrome(nasopalpebral lipoma-coloboma syndrome) Am J Med Genet 11:397–410, 1982

Schinzel-Gideon syndrome - localized hypertrichosis of face and digits JAAD 48:161–179, 2003

Periorbital neurofibroma Ophthalmology 103:942–948, 1996

Schwart-Jampel syndrome – facial dysmorphism, muscle stiffness, hypertrichosis of eyelids Adv Biomed Res Aug 10, 2015; Arch Ophthalmol 68:52–57, 1962

Peripheral sensory and motor neuropathy JAAD 25:767–770, 1991 Phenylketonuria – long eyelashes Plexiform neurofibroma Polycystic ovarian disease – acanthosis nigricans, acne vulgaris, hirsutism, hair loss JAAD 71:847–856, 2014; NEJM 352:1223– 1236, 2005; Clin Endocrinol 30:459–464, 1989; Am J Obstet Gynecol 29:181–191, 1935   Differential diagnosis:   Cushing’s syndrome   Hyperprolactinemia   Hypothyroidism   Late onset congenital adrenal hyperplasia – increased 17 hydroxy-progesterone   Pregnancy   Premature ovarian failure – increased FSH, increased LH, decreased or normal estradiol   Virilizing ovarian or adrenal tumor – total testosterone >200ng/ dl; DHEAS >700 ug/dl; increased androstenedione Porphyria - porphyria cutanea tarda - decreased hepatic uroporphyrinogen decarboxylase in sporadic and toxic forms, and decreased enzyme in all tissues in the hereditary form; accumulation of water soluble 8-, 7-, 6-, 5-, and 4- carboxylporphyrins; hypertrichosis of cheeks, forehead, and periorbital regions in about 2/3 of patients with PCT JAAD 48:161–179, 2003; hepatoerythropoietic porphyria AD 138:957–960, 2002; AD 116:307–313, 1980; variegate porphyria JAAD 48:161–179, 2003; hereditary coproporphyria BJD 96:549–554, 1977; Q J Med 46:229–241, 1977; BJD 84:301–310, 1971; congenital erythropoietic porphyria – lanugo hair on extremities, terminal hair on face; photodistributed bullae, hypertrichosis of face and neck, depigmented scars, milia, sclerosis of hands; mutation of URO III synthase Ped Derm 35:833–834, 2018; or GATA1 Eur J Haematol 94:491–497, 2015; Semin Liver Dis 2:154–63, 1982 Pregnancy – hirsutism J Drugs Dermatol 14:512–513, 2015 Primary cervical hypertrichosis(anterior cervical and/or midline posterior cervical)(nevoid hypertrichosis) AD 137:877–884, 2001 Pigmented hairy epidermal nevus syndrome Sem Derm 14:111– 121, 1995

Sclerotic granular cell tumor – hypertrichotic cerebriform nodule JAMA Derm 149:609–614, 2013 Scrotal hair Setleis syndrome(focal facial dermal dysplasia) – autosomal recessive; aged leonine appearance, bi-temporal scar-like defects, absent or multiple rows of upper eyelashes, eyebrows slanted up and out, scar-like median furrow of chin Ped Derm 21:82–83, 2004; BJD 130:645–649, 1994; Pediatrics 32:540–548, 1963 Stiff skin syndrome - hypertrichosis of eyebrows JAAD 48:161–179, 2003; Dermatology 190:148–151, 1995 Striated muscle hamartoma AD 136:1263–1268, 2000; Ped Derm 3:153–157, 1986 Supernumerary nipple(polythelia pilosa) – supernumerary nipple without the nipple Cutis 71:344–346, 2003 Tented eyebrows JAAD 37:295–297, 1997 Tetrasomy 13q – facies with long forehead, thick eyebrows, hypertelorism, broad nasal bridge, malposition of teeth, prominent central incisors with diastema, bilateral clinodactyly of fifth fingers Ped Derm 32:263–266, 2015 Thoracic hypertrichosis Treacher-Collins syndrome(mandibulofacial dysostosis) – partial or total alopecia of lower eyelashes, scarring alopecia, characteristic facies, malformed pinnae, extension of scalp hair onto cheeks; blind fistulae between ear and angle of mouth Am J Dis Child 113:405– 410, 1967 Tricho-rhino-phalangeal syndrome(Langer-Giedion syndrome) broad eyebrows Waardenburg's syndrome – synophrys; widow’s peak JAAD 37:295–297, 1997 Widow’s peak, ptosis, and skeletal abnormalities Am J Med Genet 33:357–363, 1989 Winchester syndrome - hypertrichosis of shoulders and arms, joint contractures, corneal opacities, systemic hyalinosis JAAD 48:161– 179, 2003

Hypertrichosis, Localized

ACQUIRED HYPERTRICHOSIS

AUTOIMMUNE OR IMMUNE DYSREGULATION Dermatomyositis, especially juvenile dermatomyositis JAAD 33:691, 1995; JAAD 31:383–387, 1994; Arch Dermatol Syphilol 57:725–732, 1948; infrapatellar hypertrichosis Ped Derm 19:132–135, 2002 Linear melorheostotic scleroderma - cutaneous lesions resemble linear morphea with hypertrichosis overlying bony lesions(hyperostosis); indurated skin overlying melorheostotic scleroderma; pain and stiffness, contracture and deformity; cutaneous changes overlying these bony lesions are of 2 types: 1) Proliferation and malformation of blood vessels and lymphatics. 2) Sclerodermatous changes; linear melorheostotic scleroderma with hypertrichosis sine melorheostosis BJD 141:771–772, 1999; AD 115:1233–1234, 1979

527

 Phenothiazines – hirsutism J Drugs in Dermatol 10:799–800, 2011  Progesterone  Prostaglandin F2alpha analog(latanoprost) eyedrops – trichomegaly(eyelash hypertrichosis) JAAD 44:721–723, 2001; Cutis 67:109–110, 2001; prostaglandin E1 ointment JAAD 64:1212–1213, 2011  PUVA Ped Derm 18:57–59, 2001   Reserpine – hirsutism J Drugs in Dermatol 10:799–800, 2011  Spironolactone  Streptomycin Ann Paediatr 174:389–392, 1950   Tacrolimus, topical Ped Derm 22:86–87, 2005  Tamoxifen – hirsutism of upper arms, shoulders and back J Drugs in Dermatol 10:799–800, 2011  Testosterone, topical or systemic - hirsutism J Drugs in Dermatol 10:799–800, 2011

Lupus erythematosus – localized hypertrichosis overlying lupus panniculitis JAAD 50:799–800, 2004

EXOGENOUS AGENTS

Scleroderma, linear Acta DV 80:62–63, 2000; with or without melorrheostosis

Chloracne Dermatol Clin 12:569–576, 1994

Cast application Ped Derm 18:57–59, 2001 Skin graft

DRUG Drug-induced – face, trunk, hands Clinics in Dermatol 11:99–106, 1993   Accutane - 13-cis retinoic acid   Acetazolamide – hirsutism Am J Ophthalmol 78:327–328, 1974  ACTH  Anabolic steroids - hirsutism J Drugs in Dermatol 10:799–800, 2011; Cutis 44:30–35, 1989  Benoxaprofen – face and extremities Br Med J 248:1228–1229, 1982  Cetuximab(epidermal growth factor receptor inhibitor) – facial, eyelash, eyebrow hypertrichosis BJD 161:515–521, 2009; JAAD 58:545–570, 2008; AD 142:1656–1657, 2006; scalp and eyelashes JAAD 62:531–532, 2010  Corticosteroids, topical JAAD 54:1–15, 2006; Ped Derm 18:57– 59, 2001   Cyclosporine Dermatologica 172:24–31, 1986   Danazol – facial hirsutism Cutis 74:301–303, 2004   Diazoxide – hirsutism Ann NY Acad Sci 150:373, 1982  Dilantin JAAD 18:721–741, 1988   Efalizumab – facial hypertrichosis BJD 158:1158–1159, 2008  Erlotinib(epidermal growth factor receptor inhibitor) – trichomegaly and increased length of eyebrows BJD 161:515–521, 2009; JAAD 58:545–570, 2008  Gefitinib(epidermal growth factor receptor inhibitor) – hypertrichosis of the tip of the nose with underlying hyperpigmentation BJD 156:1087–1088, 2007; increased length of eyebrows JAAD 58:545–570, 2008  Interferon NEJM 311:1259, 1984; eyelashes J Interferon Cytokine Res 20:633–634, 2000  Iodine JAAD 48:161–179, 2003  Latanoprost – topical – eyelash hypertrichosis Cutis 67:109–110, 2001  Methoxsalen   Methyldopa – hirsutism J Drugs in Dermatol 10:799–800, 2011  Metoclopromide – hirsutism J Drugs in Dermatol 10:799–800, 2011  Minoxidil BJD 101:593–595, 1979  Penicillin  Penicillamine

INFECTIONS OR INFESTATIONS AIDS - trichomegaly of eyelashes J Eur Acad Dermatol Venereol 11:89–91, 1998; Arch Ophthalmol 115:557–558, 1997; JAAD 25:801–804, 1991; hairy pinnae JAAD 28:513, 1993 Leishmaniasis - kala-azar - Pitaluga's sign - trichomegaly Post-encephalitis Vaccination sites JAAD 48:161–179, 2003 Varicella – transient circumscribed hypertrichosis Pediatrics 50:487–488, 1972

INFILTRATIVE LESIONS Lichen amyloidosis - personal observation

INFLAMMATORY DISORDERS Inflammation - hypertrichosis overlying any site of chronic inflammation or friction(napsack, chewing Arch Dermatol Syphilol 65:458– 460, 1952; vaccination – hairy scar following smallpox vaccination Indian J Pediatr 35:283–284, 1968; after measles vaccine Ped Derm 18:457–458, 2001; BCG, diphtheria; overlying wound, surgical excision, chronic venous insufficiency Postgrad Med 43:545–546, 1967; around burn Br J Plast Surg 32:93–95, 1979; excoriated insect bites AD 117:129–131, 1981; gonococcal arthritis, overlying osteomyelitis, with dermatitis, following varicella Paediatrics 50:487–488, 1972; linear overlying thrombophlebitis AD 124:30–31, 1988; insect bites Ped Derm 18:57–59, 2001; following radical lymphadenectomy Ped Derm 18:57–59, 2001; overlying arthritis Stevens-Johnson syndrome – acquired distichiasis Am J Med Genet 65:109–112, 1996

METABOLIC Acromegaly – hirsutism in females Adrenal hirsutism

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Chronic illnesses - liver disease, malnutrition

Pregnancy - hirsutism

Cushing’s disease – adrenal adenoma; personal observation

Pretibial myxedema JAAD 46:723–726, 2002; AD 122:85–88, 1986

Cushing's syndrome – hirsutism Semin Dermatol 3:287–294, 1984; iatrogenic Cushing’s syndrome - lanugo hair of cheeks

Starvation Thyrotoxicosis

Diabetes mellitus – pigmented hypertrichotic indurated plaques of thighs Ped Derm 24:101–107, 2007 Hirsutism – hormonal(congenital adrenal hyperplasia, polycystic ovarian disease, excess ovarian androgen release syndrome), racial, pregnancy(androgen secreting tumor, luteoma, lutein cysts) Obstet Gynecol 44:511–521, 1974; NEJM 288:118–122, 1973; polycystic ovarian disease Am J Obstet Gynecol 29:181–191, 1935

NEOPLASTIC

Hyperandrogenism – ovarian source – polycystic ovarian disease, ovarian tumors; adrenal source – congenital adrenal hyperplasia – 21-hydroxylase deficiency most common J Clin Endocrinol Metab 63:418–423, 1986; Cushing’s disease, adrenal carcinoma, adrenal adenoma Cancer 44:239–249, 1979; prolactinoma; gonadal dysgenesis(46 XY) – female genitalia with male skeletal characteristics Obstet Gyncecol 58:17–23, 1981; androgen therapy, idiopathic hirsutism Metabolism 37:281–286, 1988; Am J Obstet Gynecol 146:602–610, 1983; Steroids 63:308–313, 1998; Q Med J 43:603– 614, 1974  Postmenopausal hyperandrogenism(hirsutism and alopecia) NEJM 373 1660–1666 , 2015   Functional hyperandrogenism    Polycystic ovarian syndrome    Congenital adrenal hyperplasia   Ovarian hyperthecosis   Cushing’s syndrome   Acromegaly   Exposure to testosterone or dehyhydroepiandrestone dione sulfate   Tumor-related hyperandrogenism    Androgen-secreting adrenal adenomas and carcinomas    Androgen-secreting ovarian tumors    Metastatic neuroendocrine tumors

Becker's nevus - occurs in 0.5% of young men Derm Surg 24:1032– 1034, 1998; AD 92:249–251, 1965

Hyperprolactinemia JAAD 55:S103–104, 2006; Hypothyroidism, childhood – hypertrichosis of upper back and shoulders Liver disease, chronic – trichomegaly Malnutrition Menopause - hirsutism Metabolic syndrome - personal observation Multiple sclerosis Polycystic ovarian disease NEJM 352:1223–1236, 2005; Clin Endocrinol 30:459–464, 1989 Porphyria - porphyria cutanea tarda - decreased hepatic uroporphyrinogen decarboxylase in sporadic and toxic forms, and decreased enzyme in all tissues in the hereditary form; accumulation of water soluble 8-, 7-, 6-, 5-, and 4- carboxylporphyrins; hypertrichosis of cheeks, forehead, and periorbital regions in about 2/3 of patients with PCT NEJM 369:1356, 2013; JAAD 48:161–179, 2003; hepatoerythropoietic porphyria AD 116:307–313, 1980; variegate porphyria – protoporphyrinogen oxidase deficiency JAAD 48:161–179, 2003; Wien Klin Wochenschr 50:830–831, 1937; BMJ ii:89, 1955, hereditary coproporphyria BJD 96:549–554, 1977; Q J Med 46:229–241, 1977; BJD 84:301–310, 1971; congenital erythropoietic porphyria – lanugo hair on extremities, terminal hair on face Semin Liver Dis 2:154–63, 1982 Precocious puberty – premature adrenarche with molecular defects of CYP21 gene J Clin Endocrinol Metab 84:1570–1574, 1999; 37 patients with NF I - optic chasm tumors J Pediar 126:364–367, 1995

ACTH-producing non-endocrine tumors Adrenal adenoma - hirsutism Adrenal carcinoma - hirsutism

Dermal dendrocyte hamartoma with stubby white hair JAAD 32:318–21, 1995 Dermatofibroma Eccrine angiomatous nevus(hamartoma) Ped Derm 23:516–517, 2006; JAAD 51:301–304, 2004 Epidermal nevus - secreting LHRH - hirsutism - AAD 97; Ped Derm section Fibromatosis colli – hypertrichosis overlying Ped Derm 27:530–531, 2010 Fibrous hamartoma of infancy - hyperpigmented hypertrichotic hyperhidrotic plaque JAAD 64:579–586, 2011; J Pediatr Surg 46:753–755, 2011; J Cutan Pathol 34:39–43, 2007; Ped Pathol 14:39–52, 1994; Med Cutan Ibero Lat Am 18:175–177, 1990 Granular cell schwannoma Ped Derm 27:545–546, 2010 Hair follicle nevus – pre-auricular hairy papule; hair collar sign AD 148:266–268, 2012 Hairy Pacinian neurofibroma(nerve sheath myxoma) JAAD 18:416–419, 1988 Lipoblastomas – multiple subcutaneous nodules with overlying hyperpigmentation, milia, and hypertrichosis Ped Derm 34:180–186, 2017; BJD 143:694, 2000 Melanocytic nevus – compound, intradermal, congenital; congenital melanocytic nevus - cobblestoned, cerebriform, localized hypertrichosis, hyperpigmented discrete annular plaque JAAD 68:441–451, 2013; congenital melanocytic nevus with white halo NEJM 370:262, 2014 Metastatic adenocarcinoma Clin Exp Dermatol 20:237–239, 1995 Neurofibromas, periorbital Ophthalmology 103:942–948, 1996; plexiform neurofibroma Ped Derm 24:250–252, 2007 Nevoid hypertrichosis(hair follicle nevus, hairy nevus), primary; secondary nevoid hypertrichosis associated with lipodystrophy, hemihypertrophy, scoliosis, vascular abnormalities Nevus sebaceous with hair collar sign - congenital pedunculated lesion of scalp with surrounding long dark hair Ped Derm 27:525– 526, 2010 Nevus spilus – hairy nevus spilus; seen in PHACES syndrome, phakomatosis pigmentokeratotica, phakomatosis pigmentovascularis Ped Derm 30:100–104, 2013 Ovarian tumors – arrhenoblastoma, granulosa-theca cell tumor, hilus cell tumor, metastatic ovarian carcinoma - hirsutism Smooth muscle hamartoma – hyperpigmentation and hypertrichosis Arch Dermatol Syphil 7:479–481, 1923 Trichofolliculoma - personal observation Unilateral nevoid hypertrichosis

Hypertrichosis, Localized

PARANEOPLASTIC DISEASES Ectopic ACTH-producing oat cell carcinoma - personal observation Hypertrichosis lanuginosa acquisita(malignant down) – in mild forms, confined to face; lung, colon carcinomas most common; also breast, gall bladder, uterus, urinary bladder if accompanied by acanthosis nigricans; the malignancy is always an adenocarcinoma Can Med Assoc 118:1090–1096, 1978; circumscribed in acute myelogenous leukemia Dtsch Med Wochenschr 126:845–846, 2001; synophrys JAAD 37:295–297, 1997 Virilizing Leydig cell ovarian tumor - personal observation

PRIMARY CUTANEOUS DISEASE Atopic dermatitis – friction JAAD 48:161–179, 2003 Distichiasis – isolated anomaly; autosomal dominant Am J Med Genet 65:109–112, 1996 Ectopic eyelashes(cilia) – of anterior tarsal plate on upper eyelid Ped Derm 28:55–56, 2011; Ped Derm 24:433–435, 2007 Epidermolysis bullosa, dystrophic types Ann Ital Dermatol 10:195– 196, 1995 Hairy elbows syndrome/hypertrichosis cubitus – congenital vellus hair on extensor elbows Ped Derm 27:310–311, 2010; Clin Exp Dermatol 24:497–498, 1999; Ped Derm 13:303–305, 1996; AD 132:589, 1996; AD 131:858–859, 1995; J Med Genet 7:158–160, 1970 Hairy pinnae(Hamilton’s sign) - Indians, Mediterraneans; autosomal dominant sex-linked trait; acquired hairy pinna and eyebrows in HIV disease JAAD 28:513, 1993; Hum Hered 20:486–492, 1970; AIDS, XYY, babies of diabetic mothers, diabetes mellitus JAAD 48:161– 179, 2003; carried on Y chromosome Hypertrichosis singularis(single long hair) JAAD 48:161–179, 2003 Lichen sclerosus et atrophicus – hypertrichosis of labia majora in children Trans St John’s Hosp Dermatol Soc 57:9–30, 1951; Lichen simplex chronicus JAAD 48:161–179, 2003; Linear nevoid hypertrichosis Ped Derm 25:120–122, 2008 Oral mucosal hair JAAD 15:1301–1302, 1986 Psoriasis – Renbok phenomenon; alopecia areata with hair growth within psoriatic plaques AD 148:964–965, 2012 Trichomegaly – HIV, SLE, latanoprost JAAD 48:161–179, 2003

PSYCHOCUTANEOUS DISORDERS Anorexia nervosa Factitial – lipomemembranous traumatic panniculitis with overlying hypertrichosis SKINmed 12:127–130, 2014 Habit tic Trichotillomania with trichophagia – presence of hairs within the mouth JAAD 15:614–621, 1986

SYNDROMES Alstrom syndrome – dermatologic and pigmentary retinopathy or cone-rod dystrophy; acanthosis nigricans, alopecia, hirsutism; mutation in ALMS1; subcapsular cataracts, cone-rod dystrophy, photophobia, nystagmus, blindness BJD 164:878–880, 2011 Amniotic band syndrome - personal observation Angora nevus syndrome – soft white hair JAAD 63:1–22, 2010

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Becker’s nevus syndrome – breast hypoplasia Am J Med Genet 68:357–361, 1997; supernumerary nipples BJD 136:471–472, 1997; Clin Exp Dermatol 22:240–241, 1997; hypoplastic nipples Am J Med Genet 77:76–77, 1998 Blepharocheilodontic syndrome – distichiasis Am J Med Genet 65:109–112, 1996 CANDLE syndrome(chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips(thick lips), lipoatrophy of cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of lateral forehead, gynecomastia, wide spaced nipples, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, splenomegaly, protuberant abdomen Ped Derm 28:538–541, 2011; JAAD 62:487–495, 2010 Coffin-Siris syndrome – mutation in ARID1B; extreme obesity, macrocephaly, hepatomegaly, hyperinsulinemima, polycystic ovarian syndrome, hypertrichosis, hypoplastic or absent fifth distal phalanx or nail Eur J Hum Genet 22:1327–1329, 2014 Edward's syndrome(Trisomy 18) - cutis laxa of neck, hypertrichosis of the forehead and back, hemangiomas J Med Genet 15:48–60, 1978 Familial hirsutism Familial virilization Gobello syndrome – systematized linear velvety orthokeratotic nevus, hypertrichosis and follicular hyperkeratosis, bony defects with hemihypoplasia of limbs Dermatology 201:51–53, 2000 H syndrome(low height, heart, hallus valgus, hormonal, hypogonadism, hematologic) – autosomal recessive; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; starts on feet and legs and progresses upward; hypertrichosis, short stature, facial telangiectasia, ichthyosiform changes, gynecomastia, varicose veins, skeletal deformities(camptodactyly of 5th fingers), scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, micropenis, azospermia, sensorineural hearing loss, dilated scleral vessels, exophthalmos, cardiac anomalies, hepatosplenomegaly, mental retardation; mutation in nucleoside transporter Hent3 JAAD 70:80–88, 2014; BJD 162:1132–1134, 2010; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008   Differential diagnostic considerations include:   Winchester syndrome – arthropathy, coarse facies, no hearing loss    POEMS syndrome - paraproteinemia HAIR-AN syndrome – acne, muscular physique, alopecia(hyperandrogenism), hidradenitis suppurativa, insulin-­ resistance, acanthosis nigricans AD 145:492–494, 2009; AD 133:431–433, 1997 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia , coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm

530 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hereditary gingival fibromatosis – autosomal dominant; hirsutism Oral Surg 78:452–454, 1994 Hermansky-Pudlak syndrome - trichomegaly of eyelashes, eyebrows, and arms Hurler syndrome and other mucopolysaccharidoses Hypertrichosis, coarse face, brachydactyly, obesity, and mental retardation Clin Dysmorphol 5:223–229, 1996 Hypomelanosis of Ito Dermatology 195:71–72, 1997 Infantile myofibromatosis – subcutaneous induration with overlying hypertrichosis Ped Derm 27:29–33, 2010 Lymphedema-distichiasis syndrome – double row of eyelashes; periorbital edema, vertebral abnormalities, spinal arachnoid cysts, congenital heart disease, thoracic duct abnormalities, hemangiomas, cleft palate, microphthalmia, strabismus, ptosis, short stature, webbed neck BJD 175:628–631, 2016; Ped Derm 19:139–141, 2002; Hum Genet 39:113–6, 1977 Muckle-Wells syndrome(possibly H syndrome) – hyperpigmented, hypertrichotic, sclerodermoid plaques JAAD 61:725–727, 2009 Neurofibromatosis type I - precocious puberty - 3% patients with NF I have optic chiasm tumors J Pediatr 126:364–367, 1995 Neurofibromatosis Type II - schwannomas Nevoid basal cell carcinoma syndrome(Gorlin’s syndrome) – autosomal dominant; basal cell carcinomas, basaloid follicular hamartomas, hypertrichosis, linear hyp- or hyperpigmented lesions; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microphthalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors(fibromas), mesenteric cysts, cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism, BJD 182:212–217, 2020; BJD 165:30–34, 2011; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908–912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004

liomatosis), diffuse hyperpigmentation, maculopapular brown-violaceous lesions, purple nodules AD 146:615–623, 2010; JAAD 44:324–329, 2001; JAAD 40:808–812, 1999; Cutis 61:329–334, 1998; JAAD 21:1061–1068, 1989; AD 124:695–698, 1988; JAAD 12:961–964, 1985 Reflex sympathetic dystrophy – increased hair growth Cutis 68:179–182, 2001; JAAD 35:843–845, 1996; Arch Neurol 44:555– 561, 1987 Rubinstein-Taybi syndrome – hypertrichosis of back and shoulders JAAD 46:159, 2002 Schwartz-Jampel syndrome - distichiasis Am J Med Genet 65:109–112, 1996 Segmental odontomaxillary dysplasia(HATS – hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin findings) – localized facial hypertrichosis, commissural lip cleft, hyperlinear palms, abnormal teeth, missing teeth, abnormal spacing Ped Derm 25:491–492, 2008 Stiff skin syndrome(congenital fascial dystrophy) – autosomal dominant; early age at onset; rock hard sclerodermoid changes of pelvic(buttocks and thighs) or shoulder girdle, limited joint mobility, mild overlying hypertrichosis, especially over lumbosacral area and pelvic girdle Rheumatology 48:849–852, 2009; –AD 144:1351– 1359, 2008; Ped Derm 20:339–341, 2003; Ped Derm 19:67–72, 2002; Dermatology 190:148–151, 1995; Ped Derm 2:87–97, 1984; Pediatrics 47:360–369, 1971 Treacher-Collins syndrome - facial hypertrichosis

TOXINS Acrodynia – limbs Acta Paediatr Scand 40:59–69, 1951

TRAUMA Burn Chewing trauma in mentally disabled Arch Dermatol Syphilol 65:458–463, 1952 Dermatophagia("wolf-biter") Cutis 59:19–20, 1997 Fractures – after plaster casting JAAD 48:161–179, 2003; Ped Derm 18:57–59, 2001 Friction – sack bearers, habitual biting Ped Derm 18:57–59, 2001 Hypertrophic scars following knee replacement surgery JAAD 50:802–803, 2004

Nicolaides-Baraitser syndrome – congenital hypotrichosis, unusual facies(inverted triangular shaped face, low frontal hairline, mild facial hirsutism, deep set eyes, pointed nasal tip, thin nasal bridge, high arched palate, thick lower lip), interphalangeal swelling, short metacarpals(“drumstick fingers”), growth and mental retardation JAAD 59:92–98, 2008

Irritation Ped Derm 18:57–59, 2001

Noonan’s syndrome – low hairline - personal observation

Shock AD 71:401–402, 1955

Oculocerebral cutaneous syndrome

Status/post surgery, burn, insect bites, vaccination sites, eczema in children, thrombophlebitis, healed epidermolysis bullosa, occlusion with orthopedic plaster casting; varicella scars, sites of wart removal Pediatr 50:487–488, 1972

Pachyonychia congenita type II - bushy eyebrows; natal teeth, follicular keratoses, angular cheilitis, unruly hair BJD 159:500–501, 2008; Ped Derm 14:491–493, 1997

Laser – hair induction(localized hypertrichosis at site adjacent to laser-assisted hair removal) JAAD 54:64–67, 2006 Post-traumatic Radiation

Persistent adrenarche syndrome – hirsutism POEMS syndrome(Takatsuki syndrome, Crowe-Fukase syndrome) – hirsutism(hypertrichosis of head and legs), osteosclerotic bone lesions, peripheral polyneuropathy, hypothyroidism, and hypogonadism; sclerodermoid changes(thickening of skin), either generalized or localized(legs), cutaneous angiomas, blue dermal papules associated with Castleman’s disease(benign reactive angioendothe-

VASCULAR Arteriovenous fistulae Cutaneous hyperemia

Hypohidrosis (Anhidrosis) Glomuvenous malformation(plaque-type glomus tumor) – blue plaque with hypertrichosis JAAD 58:S92–93, 2008 Klippel-Trenaunay-Weber syndrome Cutis 60:127–132, 1997 Lymphedema – lower extremity lymphedema with hypertrichosis in lymphatic filariasis Trans R Soc Trop Med Hyg 90:671–674, 1996; Post-phlebitic linear hypertrichosis AD 124:30, 1988 Pseudo-Kaposi's sarcoma due to arterio-venous fistula(StewartBluefarb syndrome) – ulcerated purple plaque Ped Derm 18:325– 327, 2001; AD 121:1038–1040, 1985; arteriovenous malformation of leg with multiple fistulae and port wine stain-like purplish lesions(Mali’s acroangiodermatitis/pseudo-Kaposi’s sarcoma) – brown macules, purple nodules and plaques, edema, varicose veins, hypertrichosis, cutaneous ulcers, enlarged limb JAAD 65:893–906, 2011 Sinus pericranii – communication of extracranial veins with intracranial venous system – hair collar sign Ped Derm 31:397–399, 2014 Tufted angioma(congenital self-healing tufted angioma) – hypertrichotic indurated plaque Ped Derm 28:577–578, 2011 Venous malformation JAAD 48:161–179, 2003 Tufted angioma – pink and nodular or pink-red, purple or red-brown patches and plaques with superimposed papules with hypertrichosis; slowly enlarging benign vascular tumor of young people; mottled dull red macules and plaques, some with papules and nodules; neck, upper chest, and shoulders Ped Derm 35:808–816, 2018; BJD 171:474–484, 2014; Ped Derm 30:124–127, 2013; Ped Derm 19:388–393, 2002; AD 136:905–914, 2000; Ped Derm 14:53–55, 1997; lanugo hair AD 146:758–763, 2010; AD 142:745–751, 2006; Clin Exp Dermatol 17:344–345, 1992; JAAD 20:214–225, 1989

HYPOHIDROSIS (ANHIDROSIS)

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X-linked reticulate pigmentary disorder – recurrent pneumonia, bronchiectasis, chronic diarrhea, failure to thrive, diffuse reticulated hyperpigmentation, hypohidrosis, corneal disease leading to blindness; facies with unswept hair, flared eyebrows; female carriers display blaschko hyperpigmentation; POLA1 gene Ped Derm 33:602–614, 2016

CONGENITAL DISORDERS Congenital absence of eccrine glands Neonatal anhidrosis

DEGENERATIVE DISORDERS Anhidrosis – itching, burning, tingling skin due to small fiber neuropathy BJD 172:412–418, 2015 Aplasia of sweat glands

DRUG REACTIONS Drug Sif 31:109–126, 2008 Anti-cholinergics Anti-epileptics Antihistamines Antihypertensives(clonidine) Anti-vertigo medications Atropine, scopolamine – muscarinic acetylcholine receptor antagonists Bladder antispasmodics Botulinum toxins Clonidine (alpha adrenergic blockers)

see XEROSIS, ICHTHYOSIS) JAAD 24:1010–1014, 1991

5-fluorouracil Gastric anti-secretory drugs(propantheline)

DISORDERS OF ECCRINE GLANDS

Hexamethonium – nicotinic acetylcholine receptor antagonists Muscle relaxants Opioids

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Allogeneic hematopoietic cell transplant – amelanocytic anhidrotic alopecia areata-like phenotype after stem cell transplant AD 148:931–934, 2012 Autoimmune autonomic gangliopathy J Dermatol 44:1160–1163, 2017; CEN Case Rep 5:5–10, 2016 Graft vs host disease, chronic J Pathol 161:261–266, 1990 Lupus erythematosus, systemic – presenting as generalized anhidrosis Lupus 27:2296–2297, 2018 Morphea – pansclerotic morphea – hypohidrosis with anti-M3 muscarinic acetylcholine receptor antibodies BJD 178:e210–213, 2018; pansclerotic morphea BJD 175:e210–211, 2018; BJD 164:204–295, 2011 Multiple sclerosis Acta Neurol Scand 120:358–363, 2009 Scleroderma Sjogren's syndrome - secondary acquired generalized anhidrosis Curr Probl Dermatol 51:75–79, 2016; BJD 150:589–593, 2004; Clin Rheumatol 19:396–397, 2000; JAAD 16:233–235, 1987; with syringolymphoid hyperplasia JAAD 35:350–352, 1996

Phentolamine (alpha 2 adrenergic agonists) Tricyclic antidepressants Hydroxyurea – long term therapy Rinsho Kesueki 41:1214–1219, 2000 Lichenoid drug eruption – sequela Quinacrine Topiramate Epileptic Disord 15:203–206, 2013; Turk J Pediatrics 47:359–363, 2005 Zosinamide

INFECTIONS AND INFESTATIONS Botulism – autonomic dysfunction Clin Auton Res 28:67–81, 2018 Post-herpes zoster JAAD 76:160–162, 2017 Post H1N1 influenza Alin Auton Res 22:109–112, 2012 HTLV-1 infection – tropic spastic paraparesis Clin Auton Res 28:67–81, 2018 Leprosy – lepromatous, borderline – anhidrosis overlying plaques Pinta - tertiary(late phase) – hypohidrosis and atrophy with thinning and wrinkling of skin overlying large joints

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Sarcoidosis BJD 178:e59–61, 2018 Typhoid fever – post-typhoid anhidrosis Postgrad Med J 71:435– 436, 1995

Lamellar ichthyosis Genetic Skin Disorders, Second Edition, 2010, pp.28–32 Licnenoid dermatitis Histopathology 19:345–349, 1991 Scleredema adultorum JAAD 71:e99–101, 2014

INFLAMMATORY DISORDERS

Prurigo nodularis – rare syringotropic variant Eur J Dermatol 29:212–213, 2019

Dermal inflammatory conditions

Simple anhidrosis Am J Dis Child 113:477–479, 1967

Sarcoidosis BJD 178:e59–61, 2018 Stevens-Johnson syndrome Toxic epidermal necrolysis

SYNDROMES AEC syndrome(Hay-Wells syndrome) – vaginal erosions, mild hypohidrosis Ped Derm 16:103–107, 1999

METABOLIC DISORDERS Fabry’s disease – secondary acquired generalized anhidrosis Clin Exp Dermatol 40:444–445, 2015; AD 140:1440–1446, 2004; BJD 150:589–593, 2004; JAAD 17(pt 2):883–887, 1987 Miliaria Miliaria profunda – gooseflesh and hypohidrosis AD 143:1323– 1328, 2007 Necrobiosis lipoidica diabeticorum BJD 108:705–709, 1983 Panhypopituitarism Sweat gland fatigue

NEOPLASTIC DISORDERS Lymphoma – adnexotropic(syringotropic) T-cell lymphoma – generalized anhidrosis, alopecia, pruritus, Sjogren’s syndrome punctate red papules; hyperkeratotic follicular papules, punctate red papules; anhidrosis; palmoplantar keratoderma; poikiloderma vasculare atrophicans JAAD 71:926–934, 2014; Am J Surg Pathol 35:100– 109, 2011; Eur J Dermatol 15:262–264, 2005; BJD 151:216–226, 2004; AD 138:527–532, 2002; JAAD 38:493–497, 1998; BJD 130:765–769, 1994; BJD 110:95–101, 1984; Proc R Soc Med 62:157–159, 1969; syringotropic CTCL – hypopigmented alopecic plaque with follicular papules JAAD 60:152–154, 2009; granulomatous cutaneous T-cell lymphoma Indian J DV 76:686–690, 2010; Myelomatosis Porokeratotic eccrine ostial and dermal duct nevus – resemble nevus comedonicus; linear keratotic papules with central plugged pit; may be verrucous; filiform; anhidrotic or hyperhidrotic; most common on palms and soles JAAD 43:364–367, 2000; JAAD 24:300–1, 1991; Cutis 46:495–497, 1990; generalized porokeratotic eccrine ostial and dermal duct nevus - blaschko-distributed verrucous plaques; non-scarring alopecia, hypohidrosis, teeth in disarray, deafness JAAD 59:S43–45, 2008 Radiation dermatitis, chronic JAAD 54:28–46, 2006

PRIMARY CUTANEOUS DISEASES Acrodermatitis chronica atrophicans Acquired generalized idiopathic anhidrosis Curr Probl Dermatol 51:75–79, 2016; BJD 172:537–538, 2015; JAAD 71:415–428, 2014; BJD 168:430–432, 2013; Cutis 87:21–23, 2011; BJD 160:1337– 1339, 2009; BJD 150:589–593, 2004; Dermatologica 178:123–125, 1989; J Neurol 235:428–431, 1988 Atopic dermatitis BJD 141:683–688, 2002 Cholinergic urticarial Clin Exp Dermatol 36:559–560, 2011 Exfoliative dermatitis Clin Exp Derm Mar3(1):99–101, 1978

Acro-dermato-ungual-lacrimal-tooth syndrome(ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears hooked nose, sparse hair, hypohidrosis, hypoplastic breasts and nipples, urinary tract anomaliesmutation in TP63 gene(encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes Ped Derm 27:643–645, 2010; Am J Med Genet 45:642–648, 1993 Alopecia-onychodysplasia-hypohidrosis-deafness syndrome – small teeth, thick dystrophic toenails, hypohidrosis, hyperkeratosis of palms and soles, elbows and knees, sensorineural deafness Human Hered 27:127–337, 1977 Amelo-cerebro-hypohidrotic syndrome(Kohlschutter syndrome) – X-linked or autosomal recessive; hypohidrosis, hypoplastic yellow tooth enamel, epilepsy, spasticity, mental retardation Helv Paediatr Acta 29:283–294, 1974 Anhidrotic (hypohidrotic) ectodermal dysplasia(Christ-SiemensTouraine syndrome) J Family Med Prime Care 8:1263–1265, 2019; J Family Med Prime Care 7:264–268, 2018; Int J Dermatol 57:965–972, 2018; J Dermatol 26:44–47, 1999; X-linked recessive(most common) – absent or reduced sweating, hypotrichosis, and total or partial anodontia with conical pointed teeth J Med Genet 51:498–502, 2006; J Med Genet 28:181–185, 1991; autosomal recessive Ped Derm 7:242, 1990; mutation in ectodysplasin A(TNF family) Ped Derm 23:396–398,2006; mutations in EDA1, EDAR, EDARADD, WNT10A Human Mutations 32:70–72, 2011 Anhidrotic ectodermal dysplasia with T-cell immunodeficiency – conical teeth, sparse hair, hypohidrosis; mutation in NEMO with I-KB gain of function JAAD 58:316–320, 2008; NFKB1A/IKBA mutations Human Mutations 29:861–868, 2008 ANOTHER syndrome – alopecia, nail dystrophy, ophthalmic complications, thyroid dysfunction, hypohidrosis, ephelides and enteropathy, respiratory tract infections Clin Genet 35:237–242, 1989; J Pediatr 108:109–111, 1986 Basaloid follicular hamartoma syndrome - autosomal dominant; milia, comedone-like lesions, dermatosis papulosa nigra, skin tag-like lesions, hypotrichosis, multiple skin-colored, red, and hyperpigmented papules of the face in periorificial distribution, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck(zebra stripes); hypohidrosis AD 144:933–938, 2008; Cutis 78:42–46, 2006; JAAD 49:698–705, 2003; BJD 146:1068–1070, 2002; JAAD 45:644–645, 2001; JAAD 43:189–206, 2000; JAAD 27:237–240, 1992 Bazex-Dupre-Christol syndrome(X-linked dominant) - milia and comedo-like papules, congenital hypotrichosis, anhidrosis, X-linked dominant, follicular(vermiculate) atrophoderma of the face, elbows and hands, hypohidrosis, basal cell nevi and basal cell carcinomas,

Hypohidrosis (Anhidrosis) trichoepitheliomas, pinched nose, keratosis pilaris, scrotal tongue, joint hypermobility; UBE 2A gene JAAD 74:437–451, 2016; Ped Derm 28:727–728, 2011; Ped Derm 25:112–113, 2008; Ped Derm 23:149–151, 2006; BJD 153:682–684, 2005; Dermatol Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; JAAD 39:853– 857, 1998; J Med Genet 33:493–497, 1996; AD 130:337–342, 1994; Hautarzt 44:385–391, 1993; J Cutan Pathol 18:20–27, 1991; Clin Exp dermtol 6:31–41, 1981; Ann Dermatol Syphilgr(Paris) 93:241– 254, 1966; Bull Soc Franc Derm Syph 71:206, 1964 Cockayne syndrome – anhidrosis Ped Pathol 1:349–353, 1983 COG6 syndrome – hypohidrosis and intellectual disability; abnormal teeth, acquired microcephaly J Med Genet 50:431–436, 2013 Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis Ped Derm 36:939–941, 2019; JAAD 69:909–915, 2013; Ped Derm 29:756–758, 2012; JAAD 45:946–948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361– 367, 1985 Congenital ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis JAAD 63:607–641, 2010; JID 129:862–869, 2009; Am J Med Genet 75:186–189, 1998 Congenital insensitivity to pain with anhidrosis – autosomal recessive; recurrent episodic fevers, anhidrosis, absence of reaction to noxious stimuli, self-mutilation, mental retardation; type IV hereditary sensory and autonomic neuropathy BJD 156:1084–1086, 2007; Arch Neurol 8:299–306, 1963; secondary acquired generalized anhidrosis BJD 150:589–593, 2004 Congenital poikiloderma, traumatic bullae, anhidrosis, keratoderma Acta DV 59:347–351, 1979 Crisponi/CISS1 syndrome – anhidrosis in early childhood; subsequent paradoxical cold-induced sweating and scoliosis Am J Med Genet A 170A:1236–1241, 2016 Dermatopathia pigmentosa reticularis – autosomal dominant, reticulate hyperpigmentation of trunk, onychodystrophy, alopecia, oral hyperpigmentation, punctate hyperkeratosis of palms and soles, hypohidrosis; atrophic macules over joints with hypertrophic scarring Semin Cut Med Surg 16:72–80, 1997; AD 126:935–939, 1990; Hautarzt 6:262, 1960 Diabetes mellitus - secondary acquired generalized anhidrosis BJD 150:589–593, 2004 Ectodermal dysplasias, including EEC syndrome(ectrodactyly, ectodermal dysplasia, and cleft palate) BJD 94:277–289, 1976 Ectodermal dysplasia with cataracts and hearing defects(Marshall’s syndrome) – dental defects, cataracts, deafness Am J Ophthalmol 45:143–156, 1958 Ectodermal dysplasia(Hay-Wells syndrome) – ankyloblepharon, absent lower eyelashes, hypoplasia of upper lids, coloboma, seborrheic dermatitis, cribriform scrotal atrophy, ectropion, lacrimal duct hypoplasia, malaligned great toenails, gastroesophageal reflux, ear infections, laryngeal cleft, dental anomalies, scalp hair coarse and curly, sparse eyebrows, xerosis, hypohidrosis, short nose absent philtrum, flat upper lip Eur J Ped 177:1727–1731, 2018; BJD 152:365–367, 2005 Ectodermal dysplasia-skin fragility syndrome – autosomal recessive; plakophillin1 gene mutation(PKP1) – generalized erythema and peeling at birth; widespread skin fragility, alopecia of scalp and eyebrows, focal palmoplantar keratoderma with painful fissures, hypohidrosis; skin peeling; perioral fissuring and cheilitis; perianal erythema and erosions, follicular hyperkeratosis JAAD 58:452–457, 2008; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID

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122:1321–1324, 2004; BJD 145:297–307, 1999; Nat Genet 17:240–244, 1997 Ectrodactyly-ectodermal dysplasia-clefting syndrome – alopecia of scalp, eyebrows, and eyelashes, xerosis, atopic dermatitis, nail dystrophy, hypodontia with peg shaped teeth, reduced sweat glands and salivary glands, syndactyly, mammary gland and nipple hypoplasia, conductive or sensorineural hearing loss, urogenital anomalies, lacrimal duct abnormalities; TP63 mutations BJD 162:201–207, 2010; Ped Derm 20:113–118, 2003; BJD 146:216– 220, 2002; Dermatologica 169:80–85, 1984 Epidermoysis bullosa simplex with ectodermal dysplasia and skin fragility – autosomal recessive; plakophilin 1 mutation; palmoplantar keratoderma, woolly hair and alopecia, anhidrosis until first year Familial milia and absent dermatoglyphics – digital flexion contractures, webbed toes, palmoplantar hypohidrosis, painful fissured calluses, acral blistering, simian crease JAAD 59:1050–1063, 2008; Basan’s syndrome Ped Derm 29:527–529, 2012 Familial simple hypohidrosis with abnormal palmar dermal ridges Am J Med Genet 31:591–596, 1988 Franceschetti-Jadassohn-Naegeli syndrome – generalized reticulated hyperpigmentation, accentuated in neck and axillae; palmoplantar keratoderma; hypohidrosis J Rorensic Sci 59:555– 558, 2014; JAAD 28:942–950. 1993; JAAD 10:1–16, 1984; Naegeli-Franceschetti-Jadassohn syndrome variant – reticulate pigmentary dermatosis with hypohidrosis and short stature Int J Dermatol 34:30–31, 1995; JAAD 28:942–950, 1993; Clin Exp Dermatol Jun;1(2):127–140, 1976 Generalized anhidrosis, diffuse reticular hyperpigmentation, syndactyly J Dermatol 46:e154–155, 2019 Hereditary fibrosing poikiloderma with tendon contracture, myopathy, pulmonary fibrosis, and alopecia; FAM IIIB mutation – mimics Rothmund-­Thomson syndrome Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016; hypohidrosis with heat intolerance, mild palmoplantar keratoderma; poikiloderma of cheeks, alopecia, myopathy – fatty infiltration of muscles, hypohidrosis, lymphedema of hands and legs, exocrine pancreatic insufficiency, extraocular muscle weakness, tendon contractures Gene Reviews Oct 13, 2016; Orphanet J Rare Dis Oct 15, 2015; J Dermatol 46:1014–1018, 2019 Horner’s syndrome – unilateral anhidrosis, enophthalmos, ptosis, miosis JAAD 65:438–440, 2011 Hutchinson-Gilford syndrome(progeria) Am J Med Genet 82:242– 248, 1999; J Pediatr 80:697–724, 1972 Hypohidrosis and diabetes insipidus(Fleck syndrome) – hypohidrosis, hypotrichosis, diabetes insipidus, syndactyly, coloboma, disturbed hematopoiesis Dermatol Wochenschr 132:994–1007, 1955 Hypohidrosis with neurolabyrinthitis(Helwig-Larsen-Ludwigsen syndrome) AD 95:456–459, 1967 Hypoplastic enamel-onycholysis-hypohidrosis(Witkop-BrearleyGentry syndrome) – marked facial hypohidrosis, dry skin with keratosis pilaris, scaling and crusting of the scalp, onycholysis and subungual hyperkeratosis, hypoplastic enamel of teeth Oral Surg 39:71–86, 1975 Ichthyosis - congenital ichthyosiform erythroderma Incontinentia pigmenti - third stage; anhidrotic and achromic areas JAAD 47:169–187, 2002; BJD 116:839–849, 1987; reticulate hypohidrotic lines of posterior calves in stage IV Clin Exp Dermatol 30:474–480, 2005; adult Am J Med Genet A 179:1415–1419, 2019 Kirman syndrome – anhidrosis, almost total alopecia, severe mental retardation BJD 67:303–307, 1953

534 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Lelis syndrome – acanthosis nigricans with hypohidrosis, hypotrichosis, hypodontia, furrowed tongue, nail dystrophy, palmoplantar keratoderma Am J Med Genet A 149A:1612–1613, 2019 Olmsted syndrome - periorificial keratotic plaques; congenital diffuse sharply marginated transgradient keratoderma of palms and soles, onychodystrophy, constriction of digits, diffuse alopecia, thin nails, chronic paronychia, leukokeratosis of oral mucosa, linear keratotic streaks, follicular keratosis, constriction of digits(ainhum), anhidrosis, small stature; differential diagnostic considerations include Clouston hidrotic ectodermal dysplasia, pachyonychia congenita, acrodermatitis enteropathica, Vohwinkel's keratoderma, mal de Meleda, and other palmoplantar keratodermas Ped Derm 20:323–326, 2003; AD 132:797–800, 1996; JAAD 10:600–610, 1984 Osteopetrosis-lymphedema-hypohidrotic ectodermal dysplasia(OLHED-­ID)syndrome Ped Derm 31:716–721, 2014; AD 144:342–346, 2008; Curr Opin Immunol 16:34–41, 2004; Hum Mol Genet 11:2371–2375, 2002 Pachydermoperiostosis(Touraine-Solente-Gole syndrome) – palmoplantar JAAD 31:941–953, 1994; AD 124:1831–1834, 1988 Passarge syndrome Poland’s syndrome Scand J Plast Reconstr Surg 20:313–318, 1986 Rapp-Hodgkin ectodermal dysplasia – autosomal dominant; sparse hair, nails narrow and dystrophic, small stature, cleft lip or palate, hypospadius, conical teeth and hypodontia, hypohidrosis; distinctive facies; TP63 mutation BJD 163:624–629, 2010; Dermatol Online J 10:23 Nov 2004; Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968 Ross' syndrome – unilateral tonic pupils, generalized areflexia, progressive segmental anhidrosis with compensatory band of hyperhidrosis J Fam Med Prim Care 8:1500–1503, 2019; J Clin Neurosci 14:94–96, 2007; AD 142:264, 2006 Rosselli-Gulinetti syndrome – autosomal recessive, hypohidrosis, fine, dry, sparse scalp hair, dystrophic nails and teeth, cleft lip and palate, syndactyly, defects of external genitalia J Plast Surg 14:190–204, 1961 Rothmund-Thomson syndrome Eur J Dermatol 18:632–634, 2008; Dermatology 196:260–263, 1998 Sandmann-Andra syndrome – autosomal dominant, hypohidrosis, hypodontia Z Kinderheilk 82:238–255, 1959 Scleroatrophic and keratotic dermatosis of the limbs – palmoplanta Syringolymphoid hyperplasia with alopecia Int J Dermatol 50:1552– 1554, 2011; AD 143:921–932, 2007; JAAD 49:1177–1180, 2003; Proc R Soc Med 62:157–159, 2001 Trichothiodystrophy syndromes(Tay syndrome) - BIDS, IBIDS, PIBIDS – autosomal recessive; collodion baby, congenital erythroderma, sparse or absent eyelashes and eyebrows, sulfur deficient short brittle hair with tiger tail banding on polarized microscopy, trichomegaly, brittle soft nails with koilonychia, premature aging, very short stature, microcephaly, sexual immaturity, ichthyosis, photosensitivity, hypohidrosis, high arched palate, dysmyelination of white matter, bird-like facies, abnormal teeth with dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; recurrent infections with neutropenia; ocular abnormalities, osteopenia; socially engaging personality; mutation in one of 3 DNA repair genes(XPB, XPA, TTDA, or TTDN1 JAAD 63:323–328, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Pediatrics 87:571–574, 1991; Am J Med Genet 35:566–573, 1990; JAAD 16:940–947, 1987; Eur J Pediatr 141:147–152, 1984

Vogt-Koyanagi-Harada syndrome – with acquired idiopathic generalized hypohidrosis Eur J Dermatol 23:724–725, 2013 Xeroderma-talipes-enamel defect(Moynahan syndrome) – hypohidrosis, nail dystrophy, cleft palate, bilateral talipes, mental deficiency Proc R Soc Med 63:447–448, 1970 X-linked reticulate pigmentary disorder with systemic manifestations(familial cutaneous amyloidosis)(Partington syndrome II) – X-linked; rare; Xp21-22; boys with generalized reticulated muddy brown pigmentation(dyschromatosis) with hypopigmented corneal dystrophy(dyskeratosis), photophobia, coarse unruly hair, unswept eyebrows, silvery hair, hypohidrosis, recurrent pneumonia with chronic obstructive disease, clubbing; diarrhea, hypospadius, failure to thrive, female carriers with linear macular nevoid Blasckoesque hyperpigmentation Ped Derm 32:871–872, 2015; Am J Med Genet 161:1414–1420, 2013; Eur J Dermatol 18:102–103, 2008; Ped Derm 22:122–126, 2005; Semin Cut Med Surg 16:72–80, 1997; Am J Med Gen 10:65:1981

TRAUMA Sunstroke/exertional heat injury Dermatology 232:5056, 2016; J Dermatology 26:615–618, 1999

CAUSED BY PORAL OCCLUSION INFECTIONS Tinea versicolor Int J Dermatol 35:683, 1996 INFILTRATIVE DISORDERS Amyloidosis, familial Rinsho Shinkeigaku 36:1183–1185, 1996 METABOLIC DISORDERS Miliaria - post-miliaria anhidrosis Neutral lipid storage disease(Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma; thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness JAAD 17:801–808, 1987; AD 121:1000–1008, 1985 Tropical anhidrotic asthenia NEOPLASTIC DISORDERS Folliculotropic cutaneous T-cell lymphoma Ann Dermatol 26:385– 391, 2014 PRIMARY CUTANEOUS DISEASES Atopic dermatitis Bathing suit ichthyosis – rare variant of autosomal recessive lamellar ichthyosis Acta DV 94:349–350, 2014 Dermatitis, various causes Ichthyosiform eruptions Lamellar ichthyosis – marked hypohidrosis J Dermatol 45:1463– 1467, 2018; Clin Exp Dermatol 33:578–581, 2008 Lichen planus – hypohidrosis, metal allergy, lichen planus J Dermatology 44:963–966, 2017

Hypohidrosis (Anhidrosis) Non-bullous CIE(congenital ichthyosiform erythroderma)(erythrodermic lamellar ichthyosis) – autosomal recessive – sweat duct obstruction by hyperkeratosis AD 121:477–488, 1985; bathing suit ichthyosis, rare variant of autosomal recessive lamellar ichthyosis Acta DV 94:349–350, 2014

DEGENERATIVE DISEASES

Occlusion of proximal coiled ducts – PAS+ substance BJD 150:589–593, 2004

Peripheral nerve lesion

535

Congenital sensory neuropathy(Riley-Day syndrome) with anhidrosis J Oral Maxillofac Surg 45:331–334, 1987 Organic brain lesion Quadriplegia

Papulosquamous diseases, including psoriasis, exfoliative dermatitis Xerosis SYNDROMES Keratosis-ichthyosis-deafness syndrome Genetic Skin Disorders, Second Edition, 2010, pp.126–130 ABSENCE OF SWEAT GLANDS

DRUG REACTIONS Ganglion blocking and anticholinergic drugs

INFECTIONS AND INFESTATIONS Leprosy

Anhidrotic ectodermal dysplasias Congenital absence of eccrine glands Generalized idiopathic anhidrosis Ichthyosis vulgaris palmaris et plantaris Dermatologica 165:627– 635, 1982 Segmental anhidrosis PAUCITY OF SWEAT GLANDS Fabry's disease

INFLAMMATORY DISORDERS Multiple sclerosis

METABOLIC DISORDERS Diabetic neuropathy – hypohidrosis of legs with compensatory hyperhidrosis elsewhere J Dermatol 46:e292–293, 2019; Mayo Clin Proc 64:617–628, 1989

Idiopathic acquired generalized anhidrosis BJD 150:589–593, 2004; Dermatologica 178:123–125, 1989; J Neurol 235:428–431, 1988

Fabry’s disease BJD 157:331–337, 2007

Morphea

Idiopathic orthostatic hypotension

Progressive systemic sclerosis

Inflammation or tumors of hypothalamus

Hyperthermia

Scleredema adultorum JAAD 71:e99–101, 2014 Sweat gland necrosis – coma bullae Trichothiodystrophy syndromes - BIDS, IBIDS, PIBIDS – sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation JAAD 44:891– 920, 2001; Ped Derm 14:441–445, 1997 Tumors Ulcers X-linked recessive ichthyosis(steroid sulfatase deficiency) – in infancy, scaling of extensor arms and sides of trunk; then flexural scaling and of legs; large dark scaling of extensor surfaces of outer arms, outer thighs, around lower legs; flexures may be involved JAAD 62:480–485, 2010; Curr Prob Derm 14:71–116, 2002; Br Med J 1:947–950, 1966; AD 92:1–6, 1965 decreased numbers of sweat glands Recenti Prog Med 82:677–678, 1991

NEUROPATHY AUTOIMMUNE DISEASES Autoimmune autonomic ganglionopathy Sjogren’s syndrome-associated peripheral neuropathy BJD 133:716–720, 1995; Neurology 43:1820–1823, 1993; Funct Neurology 3:337–348, 1988

NEOPLASMS Bronchial carcinoma – unilateral anhidrosis; with hyperhidrosis of opposite side Eur J Dermatol 11:257–258, 2001

PARANEOPLASTIC DISORDERS Amyloid neuropathy Paraneoplastic neuropathy

PRIMARY CUTANEOUS DISEASES Chronic idiopathic anhidrosis Ann Neurol 18:344–348, 1985 Congenital insensitivity to pain with anhidrosis – mutation in NTRK1 gene encodes TrkA(receptor for nerve growth factor) Ped Derm 30:754–756, 2013; BJD 166:888–891, 2012; Am J Med Genet 99:164–165, 2001; JID 112:810–814, 1999; Cutis 60:188–190, 1997

PSYCHOCUTANEOUS DISORDERS Hysteria

SYNDROMES Adie's syndrome Autonomic insufficiency syndrome

536 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Cockayne's syndrome(cachectic dwarfism) – autosomal recessive; thin skin, dry hair, anhidrosis, short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes(enophthalmos with loss of periorbital fat), lipoatrophy of temples; canities, nail dystrophy, hair loss, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects, demyelination JAAD 75:873–882, 2016; Ped Derm 20:538–540, 2003; J Med Genet 18:288–293, 1981 Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome(EEC syndrome) Ped Derm 20:113–118, 2003 Epidermolysis bullosa simplex with cardiomyopathy – loss of dermatoglyphics, hypohidrosis; mutation in KLHL24 BJD 179:1181– 1183, 2018 Familial dysautonomia(Riley-Day syndrome)(HSANIII) Adv Ped 21:75–96, 1974Guillain-Barre syndrome Harlequin syndrome Hereditary sensory and autonomic neuropathy types II and IV – acral hypohidrosis(congenital insensitivity to pain with anhidrosis Ped Derm 19:333–335, 2002 Horner’s syndrome – blepharoptosis, miosis, facial anhidrosis, iris hypochromia; medullary infarction, syringomyelia, multiple sclerosis, intraspinal tumors, aortic aneurysm, cervical lymphadenopathy, surgery, regional anesthesia, tumors - transient unilateral hyperhidrosis and vasoconstriction of the face with subsequent anhidrosis Genetic Skin Disorders, Second Edition, 2010, pp.481; Harlequin sign – hemifacial flushing and contralateral hypohidrosis in Horner’s syndrome Ped Derm 23:358–360, 2006 Progressive isolated segmental anhidrosis without tonic pupils Reflex sympathetic dystrophy Cutis 68:179–182, 2001 Ross' syndrome - progressive segmental anhidrosis with compensatory hyperhidrosis, Adies' pupils(tonic pupil), loss of reflexes, cholinergic supersensitivity J Neurology 239:231–234, 1992; Neurology 32:1041–1042, 1982 Segmental hyperhidrosis with areflexia – diffuse loss of sweating Neurophysiol Clin 23:363–369, 1993

Hysteria Inracranial hemorrhage Ann Acad Med Singapore 45:69–70, 2016 Hypothalamic pituitary germinoma Eur J Dermatol 27:297–299, 2017 Multiple sclerosis Multiple system atrophy Continuum(Minneapolis, Miami)26:116– 137, 2020 Parkinson’s disease – global anhidrosis with preserved acral sweating Neurology 92:991–1005, 2019; Neurology June 14, 2016; Clin Auton Res 9:139–144, 1999 Pure autonomic failure Continuum(Minneapolis, Miami)26:116–137, 2020 Spinal cord injury Neurology 92:991–1005, 2019 Stroke Neurology 92:991–1005, 2019 Syringomyelia – loss of sweating over face and upper arms J Neurol Neurosurg Psychiatry 67:106–108, 1999

OTHER CAUSES Anticholinergic drugs Bazex syndrome Chemical agents

CHEMOTHERAPY Cholinergic urticaria - acquired generalized hypohidrosis BJD 143:1064–1066, 2000 Chronic idiopathic anhidrosis Ann Neurol 18:344–348, 1985 Defects of central nervous system in babies – hydrocephalus Arch Dis Child 46:444–451, 1971 Dehydration Dermotrichic syndrome – X-linked recessive, congenital atrichia, ichthyosis, hypohidrosis Am J Med Genet 44:233–236, 1992 Endoscopic thoracic sympathectomy(T2–T4) – facial and axillary anhidrosis Cutis 71:68–70, 2003 Erythromelalgia AD 142:1583–1588, 2006

TOXINS

Hypothyroidism – absence of sweating JAAD 26:885–902, 1992

Alcoholism – alcohol related peripheral neuropathy BJD 180:e35, 2019; Lancet ii:721–722, 1989

Leukemia

Angiokeratoma corporis diffusum(Fabry’s disease(alpha galactosidase A) – X-linked recessive; skin dry or anhidrotic due to peripheral nervous system disease JAAD 46:161–183, 2002; Clin Auton Res 6:107–110, 1996; JAAD 17:883–887, 1987; NEJM 276:1163– 1167, 1967

Shy Drager syndrome

Botulinum toxin injection – inhibits regional sweating Clin Auton Res 6:123–124, 1996

Mepacrine eruption

LOCALIZED HYPOHIDROSIS Adnexotropic T-cell lymphoma JAAD 38:493–497, 1998 Bazex-Dupre-Cristol syndrome – vermiculate or follicular atrophoderma of the face, elbows and hands, hypohidrosis of face and head JAAD 39:853–857, 1998; AD 130:337–342, 1994;

TRAUMA

Becker’s nevus BJD 156:766–767, 2007

Sympathectomy

Botulinum toxin injections Carbon monoxide poisoning

CENTRAL NERVOUS SYSTEM LESIONS Brain stem infarction Stroke 24:100–104, 1993 Dementia with Lewy bodies Neurology 92:991–1005, 2019 Diabetes insipidus Neurology 49:1708–1710, 1997 Hyperthermia

Cholinergic urticaria Allergol Int 66:495–496, 2017 Clove oil spillage – local anesthesia and anhidrosis Lancet Apr16:1(8329):882, 1983 Damage to sweat glands by infection, irradiation, granuloma, trauma, tumors, morphea, scars, inflammation, localized denervation, vitiligo

Hypopigmented Patches or Plaques Harlequin syndrome (rare autonomic disorder) – damage to sympathetic innervation of one side of face; decreased sweating and flushing on one side of face; compensatory increased sweating and flushing on normal side of face; unilateral face and upper trunk anhidrosis Auton cneurosci Sept 2019 220:102559.doi:101016/j. autneu 2019.102559; J Stroke Cerebrovasc Dis 28:e127–128, 2019; Pan Afr Med J June 25, 2019; Ann Vasc Surg Nov 2017;267:e7– e267; Indian J DV Leprol 83:740, 2017; BJD 169:954–956, 2013; associate thyrocervical trunk aneurysm, extrinsic ganglion compression; large schwannoma, apical pulmonary mass Thorax 70:605– 606, 2015 Herpes zoster JAAD 76:160–162, 2017 Holmes-Adie syndrome Neurology 17:763–769, 1967 Horner’s syndrome Intern Med 52:1757–1758, 2013 Incontinentia pigmenti – anhidrotic and achromians lesions BJD 116:839–849, 1987 Lymphoma – syringotropic cutaneous T-cell lymphoma JAAD 61:133–138, 2009 Poland syndrome- absent pectoralis major muscle and associated ipsilateral chest wall and upper extremity anomalies; anhidrosis due to absent sweat glands Am J Clin Dermatol 16:295–301, 2015 Progressive isolated segmental anhidrosis Arch Neurol 39:172–175, 1982

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Dermatomyositis – facial hypopigmentation in juvenile dermatomyositis Ped Derm 19:132–135, 2002; dermatomyositis with anti-transcriptional intermediary factor-1gamma antibodies – hypopigmented and telangiectatic patches(red and white patches); palmar hyperkeratotic papules; psoriasiform plaques JAAD 72:449–455, 2015 DiGeorge’s syndrome BJD 178:335–349, 2018 Graft vs. host disease – hypopigmented patches or total leukoderma BJD 134:780–783, 1996; chronic GVHD – butterfly depigmentation BJD 165:435–437, 2011 Lupus erythematosus – systemic lupus – large areas of hypopigmentation; vitiligo-like patches after resolution of subacute cutaneous LE JAAD 44:925–931, 2001; SCLE JAAD 33:828–830, 1995; Z. Hautkr 69:123–126, 1994; discoid LE; neonatal LE; Clin Exp Dermatol 19:409–411, 1994; papulonodular mucinosis of SLE – hypopigmented or skin colored papules and nodules AD 140:121–126, 2004 Mixed connective tissue disease Morphea; generalized morphea linear morphea Int J Derm 35:330–336, 1996; en coup de sabre JAAD 61:174–176, 2009; morphea profunda with overlying hyper- or hypopigmentation Ped Derm 8:292–295, 1991; pansclerotic morphea – mutilating form of morphea AD 116:169–173, 1980 Scleroderma Clin Dermatol 7:1–10, 1989

Prurigo nodularis Eur J Dermatol 29:212–213, 2019

Sjogren’s syndrome

Sarcoid - syringotropic sarcoid with localized hypohidrosis JAAD 68:1016–1021, 2013

Subacute combined immunodeficiency(SCID) – oval and annular generalized patches of hypopigmentation Ped Derm 26:162–168, 2009

Scleroatrophic syndrome of Huriez - 50% of patients with hypohidrosis Ped Derm 15:207–209, 1998

X-linked agammaglobulinemia BJD 178:335–349, 2018

Scleroderma Segmental anhidrosis associated with unilateral adenocarcinoma of the lung; with compensatory hyperhidrosis on contralateral chest wall JAAD 65:438–440, 2011 Sjogren's syndrome JAAD 16:233–235, 1987; associated neuropathy Neurology 43:1820–1823, 1993 Sympathetic nerve dystrophy – anhidrosis with xerosis JAAD 49:1177–1180, 2003 Syringolymphoid hyperplasia with alopecia and anhidrosis JAAD 45:127–130, 2001 Varicella – idiopathic, segmental J Dermatol 44:211–212, 2017 Vasculitis Vitiligo – segmental

CONGENITAL LESIONS Herpes simplex virus – neonatal herpes simplex presenting as multiple hypopigmented patches at birth Ped Derm 29:515–517, 2012

DRUG-INDUCED Ammoniated mercury Corticosteroids - post-steroid injection atrophy and/or hypopigmentation along draining lymphatics Ped Derm 37:235–236, 2020; JAAD 54:1–15, 2006 Gefitibib JAAD 77:902–910, 2017 Hydroxychloroquine

 YPOPIGMENTED PATCHES OR H PLAQUES

Imatinib mesylate(Gleevec)(multikinase inhibitor) – hypo- and depigmentation; hair hypopigmentation JAAD 77:902–910, 2017; JAAD 58:545–570, 2008; diffuse, patchy, or localized hypopigmentation J Pediatr Hematol Oncol 26:214, 2004; loss of lentigines AD 145:1313–1316, 2009

JAAD 80:1215–1231, 2019

Imiquimod Cutis 101:466–468, 2018

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION C1q deficiency – atrophic fingers and toes, hypopigmentation, finger tapering, butterfly rash, discoid lupus lesions, Raynaud’s phenomenon; renal disease – segmental mesangiopathic glomerulonephritis; increased interferon 1 levels Ped Derm 33:602–614, 2016 Common variable immunodeficiency BJD 178:335–349, 2018

OnabotulinumtoxinA – localized pruritus with hypopigmented linear streaks J Drugs Dermatol 14:199–200, 2014 Pembrolizumab – pruritus, hypopigmentation, morbilliform eruption, photosensitivity; including hair hypopigmentation JAAD 77:902–910, 2017; JAMADerm151:1206–1212, 2015 Pityriasis rosea-like drug eruption Retinoids Toxic epidermal necrolysis - depigmentation after toxic epidermal necrolysis JAAD 10:106–109, 1984 Vemurafenib JAAD 77:902–910, 2017

538 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

EXOGENOUS AGENTS Aluminum hypersensitivity reaction – hypopigmented subcutaneous nodules of thigh Ped Derm 34:708–710, 2017 Betel leaves – mottled hyperpigmentation evolving into confetti-like hypopigmentation JAAD 40:583–589, 1999 Chemical leukoderma Dimethylsulfate An Bras Dermatol 91(suppl1)26–28, 2016  Hydroquinone   Monobenzyl ether of hydroquinone   Monoethyl ether of hydroquinone   Monomethyl ether of hydroquinone  p-isopropylcatechol  p-methylcatechol  p-tert-butylcatechol  p-tert-butylphenol  p-tert-amylphenol  Mercaptoamines  N,N'N"-triethylenethiophosphoramide(thiotepa) Condoms – chemical hypopigmentation Facial dressings of betel pepper(piper beetle) JAAD 40:583–589, 1999 Irritant contact dermatitis to toothpaste Mercaptoethylamines

INFECTIONS AND INFESTATIONS Acquired epidermodysplasia verruciformis – hypopigmented guttate macules in immunocomprised patients JAAD 60:315–320, 2009 Bejel(endemic syphilis) – hypomelanotic macules on areola, trunk, genitalia Brown recluse spider bite – ecchymosis, ischemic pallor and erythema, livedoid necrosis, eschar JAMADerm 150:1205–1208, 2014 Herpes simplex – intrauterine presenting with hypopigmented lesions Ped Derm 29:515–518, 2012 Herpes zoster Leishmaniasis – diffuse cutaneous leishmaniasis; L. aethiopica, L. Mexicana – large hypopigmented areas, xanthomatous appearance, verruous plaques, leonine facies JAAD 73:897–908, 2015; macular post kala-azar dermal leishmaniasis; erythema and induration of butterfly region with hypopigmented macules of trunk and extremities; and infiltrated papules and nodules of forehead, chin, and central face JAAD 80:1215–1231, 2019; BJD 157:811– 813, 2007; BJD 143:136–143, 2000; JAAD 34:257, 1996 Leprosy – indeterminate – hypopigmented macules of face, arms, buttocks, or trunk JAAD 80:1215–1231, 2019; NEJM 360:160–169, 2009; Clin Inf Dis 32:930–937, 2001; tuberculoid or borderline tuberculoid – hypopigmented macule with dry, hairless anesthetic surface with fine wrinkling Int J Lepr Other Mycobact Dis 67:388– 391, 1999; lepromatous leprosy Rook p.1224, 1998, Sixth Edition; borderline lepromatous; dermatomal hypopigmented macular lesions Experientia 39:723–725, 1983 Millipede secretions – red eyes and mahogany pigmentation with bullae; heal with hypopigmentation Onchocerciasis - hypopigmented atrophic patches JAAD 45:435– 437, 2001; Cutis 65:293–297, 2000; depigmentation and atrophy AD 140:1161–1166, 2004; AD 120:505–507, 1984 Pediculosis – Vagabond’s leukoderma

Pinta – generalized cutaneous phase – hypochromic papules and patches; late secondary phase hypopigmented, depigmented hyperpigmented atrophic skin tertiary Cutis 51:425–430, 1993 Post-viral eruptive hypomelanosis JAMADerm 150:1197–1200, 2014 Schistosomiasis – ectopic cutaneous granuloma – skin colored papule, 2–3mm; group to form mamillated plaques; facial hypopigmented plaque Dermatol Clin 7:291–300, 1989; BJD 114:597–602, 1986 Streptocerciasis – Mansonella streptocerca – similar rash to onchocerciasis; acute or lichenified papules with widespread lichenification and hypopigmented macules; pruritus, lymphadenopathy JAAD 73:929–944 2015; Derm Clinics 17:151–185, 1999 Syphilis – secondary; as macular syphilid fades get depigmented macules with hyperpigmented background(leukoderma syphiliticum) on back and sides of neck(necklace of Venus) JAAD 80:1215–1231, 2019 Tinea corporis Tinea imbricata- Trichophyton concentricum – hypopigmented plaques Clin Exp Dermatol 13:232–233, 1988; Trans R Soc Trop Med Hyg 78:246–251, 1984 Tinea versicolor JAAD 80:1215–1231, 2019; NEJM 360:160–169, 2009; Semin Dermatol 4:173–184, 1985 Verrucae plana(flat warts) Yaws – secondary - lenticular hypopigmented macules; hypopigmented patches with small papules at the periphery Infect Dis Poverty Jan 30, 2020

INFILTRATIVE DISEASES Alopecia mucinosa in children – annular hypopigmented plaque with raised annular border Ped Derm 30:192–198, 2013 Amyloidosis – amyloidosis cutis dyschromica Dermatol Online J June 15, 2019 Follicular mucinosis of childhood – red facial plaques, hypopigmented facial plaques, follicular papules; alopecic scaly plaque of face(follicular mucinosis in childhood) Ped Derm 30:192–198, 2013; hypopigmented follicular papules JAAD 67:1174–1181, 2012 Langerhans cell histiocytosis – Ped Derm 35:502–506, 2018; including self-regressive Langerhans cell histiocytosis(HashimotoPritzker disease) – hypopigmented macules of trunk, solitary papules with necrosis, erosive and ulcerated papules, keratotic plantar papules JAAD 787:1035–1044, 2018; Ped Derm 27:215– 217, 2010; AD 146:667–672, 2010; AD 146:149–156, 2010 Self-healing reticulohistiocytosis – hypopigmented flat topped papules J Med Assoc Thai 97:993–997, 2014

INFLAMMATORY DISEASES Blaschkitis - personal observation Erythema multiforme Post-inflammatory hypopigmentation – in blacks, especially after dermatitis, sarcoidosis, leprosy, herpes zoster, tinea versicolor, cryotherapy, topical or injected corticosteroids NEJM 360:160–169, 2009; Int J Dermatol 29:166–174, 1990; vulvar Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 189,193 Pseudolymphoma – CD 8+ pseudolymphoma in HIV disease; widespread hypopigmentation JAAD 49:139–141, 2003 Sarcoid JAAD 80:1215–1231, 2019; JAAD 66:699–716, 2012; J Drugs Dermatol 11:385–389, 2012; AD 142:1643–1648, 2006; AD

Hypopigmented Patches or Plaques 138:259–264, 2002; AD 123:1557–1562, 1987; AD 108:249, 1973; Am J Med 35:67–89, 1963; mask-like hypopigmented plaque of posterior neck The Dermatologist; February 2015; p.47–50 Stevens-Johnson syndrome BJD 177:924–935, 2017 Sympathetic ophthalmia

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NEOPLASTIC DISEASES Basaloid follicular hamartoma - congenital systematized basaloid follicular hamartoma with microphthalmia and hemimegalencephaly; unilateral linear hypopigmented macules and streaks Ped Derm 28:555–560, 2011 Breast cancer

METABOLIC Addison’s disease – vitiligo-like patches Congenital disorders of glycosylation(CDG-I/IIx or III) – depigmented macules, café au lait macules, neurologic abnormalities Ped Derm 22:457–460, 2005 Copper deficiency – xerosis, alopecia, leukotrichia; pancytopenia, unsteady gait, distal paresthesias JAAD 80:1215–1231, 2019 Fanconi’s anemia – autosomal recessive; dyschromatosis; oral leukoplakia, oral and vulvar squamous cell carcinoma, short stature, absent radii, bone marrow failure, endocrine abnormalities, café au lait macules, guttate hypopigmentation, intertriginous hyperpigmentation, broad nose, epicanthal folds, micrognathia JAAD 54:1056– 1059, 2006 Homocystinuria – skin and hair hypopigmentation JAAD 40:279– 281, 1999 Hypogonadism JAAD 80:1215–1231, 2019 Hypopituitarism – diffuse loss of pigment JAAD 80:1215–1231, 2019 Hypothyroidism – pale, cold, scaly, wrinkled skin JAAD 26:885–902, 1992 Kwashiorkor - hypochromotrichia and hypopigmentation of skin JAMADerm 150:910–911, 2014; Cutis 67:321–327, 2001; Cutis 51:445–446, 1993 Liver disease, chronic – spotty hypopigmentation on back, buttocks, and thighs; may be in relation to spider telangiectasias Malabsorption Panhypopituitarism – pallor and fine wrinkling Pernicious anemia – vitiligo, canities Phenylketonuria – phenylalanine hydroxylase deficiency; fair skin and hair Ped Derm 23:136–138, 2006; Prolidase deficiency – autosomal recessive; peptidase D mutation(PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature(mild), telangiectasias, recurrent infections(sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; ­dermatitis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; Ped Derm 13:58– 60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987 Renal disease – nephrosis Selenium deficiency – loss of pigmentation of hair and skin Cutis 61:229–232, 1998; xerosis, alopecia, leukotrichia, leukonychia; pancytopenia, muscle weakness, muscle pain, cardiac arrhythmia, unsteady gait, distal paresthesias JAAD 80:1215–1231, 2019

Clear cell papulosis – hypopigmented or white flat-topped macules or papules in milk line and/or lower abdomen of children Ped Derm 36:655–657, 2019; JAMADerm 155:111–112, 2019; Ped Derm 35:841–842, 2018; Ped Derm 29:195–198, 2012; JAAD 63:266– 273, 2010; AD 145:1066–1068, 2009; AD 143:358–360, 2007; Ped Derm 22:268–269, 2005; Ped Derm 14:380–382, 1997; Am J Surg Pathol 11:827–834, 1987 Connective tissue nevus with elastorrhexis or upper chest - skin colored or hypopigmented or yellow papules, plaques, nodules in cobblestoned pattern Ped Derm 32:518–521, 2015 Cutaneous T-cell lymphoid dyscrasia JAAD 80:1215–1231, 2019 Dermatofibrosarcoma protuberans, congenital – annular red plaque, pink alopecic plaque, red macule, blue plaque, hypopigmented plaque AD 143:203–210, 2007 Desmoplastic hairless hypopigmented nevus(variant of giant congenital melanocytic nevus) Ped Derm 29:336–340, 2012; BJD 148:1253–1257, 2003 Disseminated hypopigmented keratoses AD 127:848–850, 1991   vs. Darier's disease   Flat warts Lichen nitidus   Psoriasis   Stucco keratoses Eccrine nevus – segmental hypopigmented patch Ped Derm 25:613–615, 2008 Epidermal nevus, epidermolytic hyperkeratosis - personal observation Extramammary Paget’s disease – white patches of vulva BJD 151:1049–1053, 2004 Halo nevus(Sutton’s nevus; leukoderma acquisitum centrifugum) AD 92:14–35, 1965 Lesions with halos AAD '97   Basal cell carcinoma   Blue nevus  Histiocytoma   Melanocytic nevus, congenital nevus  Melanoma   Metastatic melanoma  Neurofibroma   Seborrheic keratosis   Verruca plana - involuting flat wart Linear porokeratosis AD 135:1544–1555,1547–1548, 1999; Ped Derm 4:209, 1987; AD 109:526–528, 1974 Lymphoma – hypopigmented cutaneous T-cell lymphoma JAAD 80:1215–1231, 2019; J Drugs Dermatol 14193–194, 2015; JAMA 309:392–393, 2013; Ped Derm 27:607–613, 2010; Ped Derm 27:197–198, 2010; JAAD 60:359–375, 2009; NEJM 360:160–169, 2009; JAAD 49:264–270, 2003; JAAD 46:325–357, 2002; JAAD 42:33–39, 2000; J Dermatol 27:543–546, 2000; JAAD 32:987– 993, 1995; AD 128:1265–1270, 1992; in childhood Ped Derm 23:493–496, 2006; Ped Derm 14:449–452, 1997; AD 130:476– 480, 1994; JAAD 17:563–570, 1987; hypopigmentation associated with flares of erythrodermic CTCL BJD 143:832–836, 2000; Woringer-Kolopp disease JAAD 55:276–284, 2006; syringotropic CTCL – hypopigmented alopecic plaque with follicular papules

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JAAD 60:152–154, 2009; juvenile cutaneous T-cell lymphoma – hypo- and hyperpigmented patches JAAD 71:1117–1126, 2014; CD8+ cytotoxic cutaneous T-cell lymphoma Int J Dermatol Oct 21, 2019 Melanocytic nevus, including congenital melanocytic nevus - poliosis AD 129:1331–1336, 1993; desmoplastic hairless hypopigmented nevus BJD 148:1253–1257, 2003 Melanoma, primary hypopigmented melanoma Practical Dermatol May 2014,p.55; regressed melanoma JAAD 53:101–107, 2005 Melanoma(metastatic) associated leukoderma Nevus anemicus Stat Pearls Jan 17, 2020 Nevus comedonicus – areas of hypopigmentation AD 116:1048– 1050, 1980

Bier spots(physiologic anemic macules) – upper and lower extremities; disappears or less apparent with limb elevation, Wood’s light or blanching of uninvolved skin - JAAD 80:1215–1231, 2019; Cutis 81:477–478, 2008; Arch Pathol Anat 153:306–334, 1898; BASCULE – Bier anemic spots, cyanosis, with urticarial-like eruption BJD 175:218–220, 2016 Bullous dermolysis of the newborn(form of autosomal dominant epidermolysis bullosa or recessive dystrophic epidermolysis bullosa) – hypopigmented patches; giant bullae of hand and foot; erosions, tongue erosions, milia Ped Derm 30:736–740, 2013 Cutis tricolor – hyper- and hypopigmented lesions with a background of normal skin Eur J Pediatr 159:745–749, 2000

Nevus depigmentosus JAAD 55:423–428, 2006; JID 64:50–62, 1975

Darier's disease AD 142:235–240, 2006; Clin Exp Dermatol 29:313–314, 2004; Int J Derm 40:278–280, 2001; Int J Dermatol 34:390–392, 1995; Dermatol 188:157–159, 1994; AD 128:397–402, 1992

Nevus depigmentosus with lentiginosis – hypopigmentation and lentigines JAAD 54:S238–240, 2006

Dowling-Degos disease – hypopigmented macules of breast JAAD 64:1224–1225, 2011

Parapsoriasis en plaque JAAD 80:1215–1231, 2019

Epidermolysis bullosa pruriginosa(DDEB) – atrophic skin with erosions, hypertrophic scarring, hypopigmentation, and linear scars; reticulated linear hypopigmented plaques; bullae; scars; zebra stripe appearance; dyschromatosis Ped Derm 32:549–550, 2015; JAAD 56:S77–81, 2007

Trichodiscomas AD 126:1091–1096, 1990 Tumor of follicular infundibulum – facial and neck hypopigmented macules and patches(multiple) JAMADerm 152:1155–1156, 2016; Indian J Dermatol Venereol Leprol 80:141–144, 2014; J Cut Pathol 40:532–537, 2013; Dermatol Surg 30:1246–1248, 2004; AD 135:463–468, 1999; JAAD 39:853–857, 1998; JAAD 33:979–984, 1995 Waldenstrom’s macroglobulinemia – pseudoleukoderma angiospasticum; white patches from arteriolar spasm and peripheral vasodilatation Clin in Dermatol 37:610–617, 2019

PHOTODERMATOSES Acquired brachial cutaneous dyschromatosis(ABCD) Ann Dermatol 39:342–344, 2018 Actinic reticuloid Annular elastolytic granuloma – serpiginous, erythematous, annular red papules with central striking hypo- or depigmentation BJD 160:1126–1128, 2009 Persistent actinic epidermolytic hyperkeratosis JAAD 32:63–66, 1995

Eruptive hypomelanosis – under 10 years old; upper and lower extremities follows prodromal coryzal phase; spontaneous resolution JAAD 80:1215–1231, 2019 Familial white lentiginosis – hypopigmented macules BJD 177:535– 537, 2017 Febrile ulceronecrotic Mucha-Habermann disease JAAD 55:557– 572, 2006; NJAAD 54:1113–1114, 2006; Ped Derm 22:360–365, 2005;BJD 152:794–799, 2005; JAAD 49:1142–1148, 2003; BJD 147:1249–1253, 2002; Ped Derm 8:51–57, 1991; Ann DV 93:481– 496, 1966 Frontal fibrosing alopecia JAAD 76:1184–1186, 2017 Galli-Gallli disease – reticulate, hyper- and hypopigmented macules and papules; intertrigo; mutation in keratin 5 BJD 170:1362–1365, 2014 Hailey-Hailey disease - longitudinal leukonychia Hautarzt 43:451– 452, 1992 Hypermelanocytic guttate and macular segmental hypomelanosis BJD 151:701–705, 2004 Segmental hyperpigmentation disorder BJD 162:1337–1341, 2010

PRIMARY CUTANEOUS DISEASES Acquired macular hypomelanosis NEJM 360:160–169, 2009 Albinism – light skin and hair; tyrosinase negative(type IA), yellow mutant(type IB), platinum, tyrosinase positive(type II), minimal pigment(type IB-MP), temperature sensitive(type IB-TS), brown(type II), rufous(type III), Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, autosomal dominant Clin in Derm 37:561–579, 2019; JAAD 19:217–255, 1988 Albinism with deafness Albinoidism JAAD 19:217–255, 1988 Alopecia mucinosa Annular leukoderma Annular lichenoid dermatitis of youth – red-brown annular plaques with hypopigmented centers Ped Derm 27:584–585, 2010; JAAD 49:1029, 2003 Atopic dermatitis

Idiopathic guttate hypomelanosis JAAD 80:1215–1231, 2019; BJD 103:635–642, 1980  Differential diagnosis of multiple guttate hypomelanotic macules AAD '97;Bolognia   Amyloidosis, biphasic    Darier's disease(admixed with keratotic lesions)    Idiopathic guttate hypomelanosis    In association with keratosis punctata    In association with chromosomal abnormalities    Disseminated hypopigmented keratoses(flat-topped papules)    Lichen sclerosus et atrophicus   Pityriasis alba    Pityriasis lichenoides chronica    PUVA therapy with leukoderma punctata    Tuberous sclerosis - confetti-like hypopigmentation Leukoderma punctata – including following PUVA therapy JAAD 80:1215–1231, 2019 Lichen planus

Hypopigmented Patches or Plaques Lichen sclerosus et atrophicus - genital or guttate extragenital Ped Derm 36:711–712, 2019 Lichen simplex chronicus Lichen striatus - personal observation Lichen striatus-like leukoderma J Eur Acad DV 10:152–154, 1998 Lipodystrophia centrifugalis abdominalis Ped Derm 21:538–541, 2004; AD 104:291–298, 1971 Midline hypopigmentation of blacks – line, band, or discrete oval macules of anterior chest, mid-sternal area; abdomen, neck Int J Dermatol 12:229–235, 1973 Parapsoriasis en plaque, hypopigmented JAAD 67:1182–1188, 2012 Phylloid hypomelanosis – associated with trisomy 13 mosaicism BJD 174:741–752, 2016; Eur J Dermatol 10:511, 2002; Hautarzt 52:3–5, 2001; mental retardation, short stature, scoliosis, facial dysmorphism, asymmetric leg lengths Ped Derm 14:278–280, 1997; phylloid hypo- and hyperpigmented macules Am J Med Genet 98:145–147, 2001 Pigmentary demarcation lines, group C and E Pityriasis alba JAAD 80:1215–1231, 2019; BJD 155:152–155, 2006; Pityriasis lichenoides chronica(guttate parapsoriasis) Clin in Dermatol 37:561–579, 2019; Cutis 85:125–129, 2010; JAAD 56:205–210, 2007; Pityriasis rosea

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Alezzandrini's syndrome – unilateral degenerative retinitis, ipsilateral facial vitiligo and poliosis, with or without deafness Ophthalmologica 147:409–419, 1964 Angelman syndrome - hypopigmentation, mental retardation Am J Med Genet 40:454, 1991 Ankyloblepharon-ectrodactyly-cleft lip/palate(AEC) syndrome – hyper- and hypopigmentation AD 141:1591–1594, 2005 Apert's syndrome – albinoid skin, craniodysostosis, cutaneous and ocular hypopigmentation, midface malformation, symmetric syndactyly, severe acneform eruptions, seborrhea AD 128:1379– 1386, 1992 Ataxia telangiectasia - premature graying of hair JAAD 10:431–438, 1984; hyperpigmented macules, hypopigmented macules, café au lait macules BJD 144:369–371, 2001; autosomal recessive; telangiectasias of face, ocular telangiectasia, extensor surfaces of arms and bulbar conjunctiva; melanocytic nevi, facial papulosquamous rash, hypertrichosis, bird-like facies; immunodeficiency, increased risk of leukemia, lymphoma; cerebellar ataxia with eye movement signs, mental retardation, and other neurologic defects; cafe au lait macules JAAD 68:932–936, 2013; Ann Int Med 99:367–379, 1983 Atrichia with popular lesions – hypopigmented white streaks of scalp; milia JAAD 59:1050–1063, 2008 Basaloid follicular hamartoma syndrome – hypopigmented papules of face Ped Derm 16:281–284, 1999

Pityriasis rotunda JAAD 31:866–871, 1994

Blacklock's albinism deafness syndrome(BADS)

Progressive macular hypomelanosis JAAD 80:1215–1231, 2019; Ped Derm 29:460–462, 2012; J Drugs Dermatol 10:502–506, 2011; JAAD 60:359–375, 2009; Ped Derm 25:63–65, 2008; JAAD 55:836–843, 2006; AD 140:210–214, 2004; Bull Soc Pathol Exot 90:333–334, 1997; Ann DV 121:880–883, 1994; J Cutan Pathol 15:286–289, 1988; hypopigmentation of face Cutis 101:297–300, 2018

Book syndrome - hyperhidrosis, premature graying, and premolar hypodontia

Psoriasis Woronoff’s ring Seborrheic dermatitis JAAD 80:1215–1231, 2019 Syringolymphoid hyperplasia with alopecia AD 143:921–932, 2007; JAAD 49:1177–1180, 2003; Proc R Soc Med 62:157–159, 2001 Tetragametic chimerism(“cutis bicolor”) – hyper- and hypopigmentation(Blaschko) AD 144:327–330, 2008 Transient bullous dermolysis of the newborn Ped Derm 20:535–537, 2003 Vitiligo NEJM 360:160–169, 2009; hypochromic vitiligo BJD 172:716–721, 2015

PSYCHOCUTANEOUS DISORDERS Delusions of parasitosis – hypopigmented scars with excoriations NEJM 371:2115–2123, 2014 Factitial dermatitis – focal hyper- and hypopigmentation due to factitial inhaler(salbutamol) exposure Ped Derm 24:499–500, 2007 Skin picking – linear hypopigmented scars JAAD 76:779–791, 2017

SYNDROMES Acroleukopathy – hypopigmentation around nailfolds and distal interphalangeal joints AD 92:172–173, 1965 Acropigmentation symmetrica of Dohi JAAD 45:760–763, 2001; JAAD 10:1, 1984

Bloom's syndrome - hypopigmented macules; large café au lait macules JAAD 75:855–870, 2016; BJD 164:245–256, 2011; Ped Derm 14:120–124, 1997

Brachymetapody syndrome(Tuomaala-Haapanen syndrome) – albinoid skin – short stature, shortening of all digits but thumbs, hypoplastic maxilla, anodontia, hypotrichosis, hypoplastic breasts and genitalia, strabismus, distichiasis Syndromes of the Head and Neck, p. 834, 1990; Acta Ophthalmol 46:365–371, 1968 Carney complex – hypopigmented lesion of lips; PRKAR1alpha JAMADerm 150:760–763, 2014 Chediak-Higashi syndrome – autosomal recessive; partial albinism, silvery hair, large azurophilic leukocyte inclusions, photophobia, hypopigmentation, early death(before age 20), recurrent pyogenic sinopulmonary infections; smaller pigment clumps; defective transfer of melanosomes BJD 178:335–349, 2018; Ped Derm 34:607–608, 2017; Ped Derm 28:494–501, 2011; Ped Derm 24:182–185, 2007; JAAD 55:337–340, 2006; Curr Prob Derm 14:41–70, 2002; JAAD 19:217–255, 1988 CHILD syndrome - congenital hemidysplasia, ichthyosis, limb defects, ichthyosiform erythroderma with verruciform xanthoma, linear eruptions, and hypopigmented bands Ped Derm 15:360–366, 1998 Chromosome 5p defect Cole’s disease – generalized hypopigmented macules with punctate keratoses of the palms and soles; mutation in ENPP1 encoding endonucleotide pyrophosphatase/phosphodiesterase BJD 174:1152–1156, 2016; JID 67:72–89, 1976; AD 145:495–497, 2009; Ped Derm 19:302–306, 2002; JID 67:72–89, 1976; AD 112:998– 1000, 1976 Congenital poikiloderma with unusual hypopigmentation and acral blistering at birth J Eur Acad Dermatol Venereol 12:54–58, 1999 Conradi-Hunermann syndrome - X-linked dominant; mutation in EBP(emopamil-binding protein); mutation in cholesterol metabolism;

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

collodion baby; ichthyosiform erythroderma, linear and whorled(Blaschko-esque) hyperkeratotic bands with diffuse erythema and scale, follicular atrophoderma, atrophic hypochromic areas, patchy scalp alopecia; cataracts, short stature, asymmetric short arms and legs, chondrodysplasia punctata(stippled epiphyses), vertebral defects with scoliosis, cataracts AD 147:1073–1076, 2011; BJD 160:1335–1337, 2009; BJD 157:1225–1229, 2007; Ped Derm 15:299–303, 1998; AD 127:539–542, 1991; JAAD 21:248– 256, 1989; Hum Genet 53:65–73, 1979 Constitutional mismatch repair deficiency syndrome(CMMR-D) – café au lait macules; hypopigmented macules; hematologic malignancies, rhabdomyosarcoma, brain tumors, early onset gastrointestinal tumors; mutations in MLH1, MSH2, MSH6, OR PMS2 BJD 164:245–256, 2011; Hum Genet 124:105–122, 2008; Eur J Hum Genet 16:62–72, 2008; J Med Genet 46:418–420, 2009 CRIE syndrome - congenital reticulated ichthyosiform erythroderma – formerly ichthyosis en confetti(includes ichthyosis variegate, MAUIE syndrome) JAMADerm 151:64–69, 2015; JAMADerm 151:15–16, 2015; Acta DV 94:579–582, 2014; Dermatology 188:40–45, 1994 Cronkhite-Canada syndrome – hyper- and hypopigmented macules of dorsal fingers; onychomadesis, diffuse hair loss, diarrhea, weight loss, polyposis of stomach, duodenum, colon; hypoproteinemia JAAD 63:172–174, 2010; Cutis 61:229–232, 1998 Cross-McKusick-Breen syndrome(oculocerebral syndrome with hypopigmentation) – autosomal recessive; albino-like hypopigmentation, silver-gray hair, gingival fibromatosis, microphthalmos, opaque cornea, nystagmus, spasticity, mental retardation; post-natal growth retardation J Pediatr 70:398–406, 1967 Cutis tricolor parvimaculata(twin spotting – didymosis) – small café au lait macules and hypopigmented macules; ring chromosome 15 syndrome; low birth weight, failure to thrive, microcephaly, triangular face, clinodactyly, mental retardation Ped Derm 28:670–673, 2011; Dermatology 211:149–151, 2005 Depigmented bilateral Blaschko hypertrichosis with dilated follicular orifices and cerebral and ocular malformations BJD 142:1204– 1207, 2000 Ectrodactyly-ectodermal dysplasia-clefting syndrome(EEC syndrome) – albinoid skin Clin Genet 3:43–51, 1971; hypopigmented wiry sparse hair JAAD 53:729–735, 2005 Elejalde syndrome(neuroectodermal(neurocutaneous)melanolysosomal disease) - silvery hair, bronze colored skin, generalized hypopigmentation; profound central nervous system dysfunction(seizures, hypotonia); hypotonic facies, plagiocephaly, micrognathia, crowded teeth, narrow high palate, pectus excavatum, cryptorchidism; normal immune system; defective transfer of melanosomes JAAD 55:337–340, 2006; JAAD 38:295–300, 1998; Am J Med Genet 3:65–80, 1979 Epidermodysplasia verruciformis – hypopigmented macules JAAD 76:1161–1175, 2017; Ped Derm 24:511–513, 2007; Cutis 79:307– 311, 2007; JAAD 49:S262–264, 2003; hypopigmented scaling patches AD 146:667–672, 2010; Arch Dermatol Syph 141:193–203, 1922 Familial gigantic melanocytosis(familial melanopathy with gigantic melanocytes) – diffuse brown hyperpigmentation with raindrop hypopigmentation, light colored scalp and body hair; sparse pubic and axillary hair; large melanocytes filled with late stage melanosomes; TMC6, TMC8, RHOH, CORO1A, IL-7, MST-1 Int J Derm 44:1010–1015, 2005; Am J Dermatopathol 6:31–34, 1984 Familial hyper- and hypopigmentation with age-related pattern change(cutis tricolor) – multiple hypopigmented macules and patches with hyperpigmented patches; as patient ages see smaller

hyper- and hypopigmented macules and hyperpigmented patches BJD 175:1369–1371, 2016; Am J Med Genet A 15:132A:215–218, 2005; Eur J Dermatol 13:343–345, 2003 Fanconi’s anemia – autosomal recessive; endocrine abnormalities with hypothyroidism, decreased growth hormone, diabetes mellitus, café au lait macules, diffuse hyperpigmented macules, guttate hypopigmented macules, intertriginous hyperpigmentation, skeletal anomalies(thumb hypoplasia, absent thumbs, radii, carpal bones), oral/genital erythroplasia with development of squamous cell carcinoma, hepatic tumors, microphthalmia, ectopic or horseshoe kidney, broad nose, epicanthal folds, micrognathia, bone marrow failure, acute myelogenous leukemia, solid organ malignancies(brain tumors, Wilms’ tumor) BJD 164:245–256, 2011; JAAD 54:1056–1059, 2006 Focal dermal hypoplasia, morning glory anomaly, and polymicrogyria – swirling pattern of hypopigmentation, papular hypopigmented and herniated skin lesions of face, head, hands, and feet, basaloid follicular hamartomas, mild mental retardation, macrocephaly, microphthalmia, unilateral morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly Am J Med Genet 124A:202–208, 2004 Goltz's syndrome (focal dermal hypoplasia) - protruding ears, mid-facial hypoplasia, pointed chin, lower limb hypoplasia, blaschkoesque atrophy, red and hypopigmented blaschko streaks, painful exophytic granulation tissue, giant cell tumor of bone(large subcutaneous nodule) BJD 160:1103–1109, 2009; male mosaic Goltz’s syndrome; blaschko-­linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011 Griscelli's syndrome – autosomal recessive; silvery hair, eyelashes, and eyebrows, partial albinism(hypopigmented skin), neurologic abnormalities(hypotonia, spasticity, mental retardation, seizures), and immunodeficiency; pyogenic infections of skin and internal organs; hemophagocytic syndrome with uncontrolled T-cell macrophage hyperactivation(type 3 – melanophillin); large pigment granules in hair shaft; mutation in myosin Va gene – organelle transport(type 1-MYO5A; type 2 – RAB27A); defective transfer of melanosomes; type 1 – severe neurologic abnormalities but no immune defects; type 2 – less severe neurologic defects with immune defects; type 3 – no neurologic or immune defects JAMA 308:617–618, 2012; JAAD 55:337–340, 2006; J Clin Immunol 22:237–243, 2002; Am J Hum Genet 71:1237–1238, 2002; JAAD 38:295–300, 1998; Semin Cut Med Surg 16:81–85, 1997; Am J Med 65:691–702, 1978 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas; ipsilateral hypertrichosis; hypo- and hyperpigmentation; linear atrophoderma; osseous, dental, and/or cerebral defects BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221–225, 2009; Acta DV 88:382–387, 2008 Hermansky-Pudlak syndrome – oculocutaneous albinism, hemorrhage, ceroid-like material deposited in several organs; granulomatous colitis, pulmonary fibrosis, renal failure, cardiomyopathy, hypothyroidism Ped Derm 34:638–646, 2017; SKINmed 12:313–315, 2014 Horner’s syndrome Hutchinson-Gilford syndrome Hypomelanosis of Ito(incontinentia pigmenti achromians) – whorled depigmented patches in Blaschko pattern; associated musculoskeletal, teeth, eye, and central nervous system abnormalities JAAD 19:217–255, 1988 Ichthyosis en confetti(congenital reticulated ichthyosiform erythroderma) – reticulated erythroderma with guttate hypopigmentation, palmoplantar kertoderma; loss of dermatoglyphics; temporary hypertrichosis of normal skin BJD 166:434–439, 2012; JAAD 63:607–641, 2010

Hypopigmented Patches or Plaques Incontinentia pigmenti - stage IV - hypopigmented streaks on the legs of women; achromic and anhidrotic areas JAAD 47:169–187, 2002; BJD 116:839–849, 1987 Klein-Waardenburg syndrome KLICK syndrome(keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; Acta DV 77:225–227, 1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989 Menkes' kinky hair syndrome - silvery hair, generalized hypopigmentation, lax skin of brows, neck, and thighs Cutis 90:170–172, 2012; JAAD 59:1–22, 2008; Ped Derm 15:137–139, 1998; carrier state with hypopigmented swirls and streaks Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of neck and trunk; depigmentation(nevus depigmentosus); small pointed widely spaced teeth; low set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Mosaic tetrasomy 13q – oval oblong hypopigmented patch; phylloid hypomelanosis Ped Derm 32:263–266, 2015 Muckle-Wells syndrome(possibly H syndrome) – hyperpigmented, hypertrichotic, sclerodermoid plaques JAAD 61:725–727, 2009 Multiple endocrine neoplasia syndrome(MEN I) – angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia; mutation in menin, a nuclear protein involved in cell cycle regulation and proliferation JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004; AD 133:853–857, 1997 Neurofibromatosis – nevus anemicus JAAD 69:768–775, 2013 Nevoid basal cell carcinoma syndrome with type 2 mosaicism – Blaschko-esque atrophy, Blaschko-esque pits of palms; linear papules of foot; white papules and plaques; segmental hyper- and hypopigmented patches BJD 182:212–217, 2020; BJD 169:1342– 1345, 2013 Oculocerebral syndrome with hypopigmentation of Cross-McCusick-­ Breen – generalized hypopigmentation with microphthalmia, corneal opacities; mental retardation and spasticity Birth Defects 11:466– 467,1975; J Pediatr 70:398–406, 1967 Oculocerebral hypopigmentation syndrome of Preus – very short with thin build, ptosis, high arched palate, dental malocclusion, prominent central upper incisors, hair and skin hypopigmented, deafness, severe mental retardation with ataxia, decreased deep tendon reflexes, myopia, lens opacities, acetabular hypoplasia, and cerebral atrophy(especially occipital lobes) Ped Derm 24:313–315, 2007; J Genet Hum 31:323–328, 1983 Oculocutaneous albinism   Tyrosinase negative   Yellow mutant  Platinum   Tyrosinase positive  Minimal  Brown  Rufous

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 Hermansky-Pudlak Ped Derm 15:374–377, 1998  Chediak-Higashi   Autosomal dominant  OCA1A – white hair and hypopigmentation BJD 166:896–898, 2012 Osteopathia striata with pigmentary dermopathy including white forelock Pallister-Killian syndrome(mosaic tetrasomy 12p) – mental retardation, coarse facies with hypertelorism and prominent forehead, sparse temporal hair and high frontal hairline, hypo- and hyperpigmentation, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i(12p)(tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005;J Clin Dysmorphol 1:2–3, 1983 Parry-Romberg syndrome Ped Derm 21:48–50, 2004; JAAD 22:531–533, 1990 Patton syndrome – hypopigmentation, mental retardation, ataxia, myopia, occipital, cerebral atrophy, coxa valga, osteoporosis J Med Genet 24:118–122, 1987 Phakomatosis pigmentovascularis – nevus anemicus Dermatology 198:327–329, 1999 Phylloid hypomelanosis(Happle) – leaf-shaped lesions; trisomy 13; mental retardation, hearing loss, craniofacial defects, skeletal abnormalities Am J Med Genet 85:324–329, 1999; Ped Derm 14:278–280, 1997; mosaic partial trisomy 13 – phylloid hypomelanosis, mental retardation, agenesis of the corpus callosum, conductive hearing loss, coloboma, skeletal defects, syndactyly, clinodactyly, dental malposition, oligodontia, pre-auricular fistulae AD 145:576–578, 2009 Piebaldism – autosomal dominant; white forelock, white patches on upper chest, abdomen, extremities with islands of hyperpigmentation within JAAD 44:288–292, 2001; mutations and deletions of c-kit(steel factor receptor) Am J Hum Genet 56:58–66, 1995 Piebaldism and Hirschsprung's disease Piebald trait with neurologic defects POEMS syndrome AD 123:85–87, 1987 Prader-Willi syndrome – albinoid skin; almond-shaped eyes, narrow bifrontal diameter, thin upper lip, short stature, central obesity, small hands and feet, mental retardation, hypogonadism, hypotonia at birth, excoriations, trichotillomania Cutis 90;129–131, 2012; Growth Genet Hormones 2:1–5, 1986; Schweiz Med Wschr 86:1260–1261, 1956 Progressive spastic parapesis, vitiligo, premature graying, and distinct facial appearance Proteus syndrome – port wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation Am J Med Genet 27:87–97, 1987; Pediatrics 76:984–989, 1985; Eur J Pediatr 140:5–12, 1983 Rapp-Hodgkin hypohidrotic ectodermal dysplasia - autosomal dominant; alopecia of wide area of scalp in frontal to crown area, short eyebrows and eyelashes, coarse wiry sparse hypopigmented scalp hair, sparse body hair, scalp dermatitis, ankyloblepharon, syndactyly, nipple anomalies, cleft lip and/or palate; nails narrow and dystrophic, small stature, hypospadius, conical teeth and anodontia or hypodontia; distinctive facies, short stature JAAD

544 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 53:729–735, 2005; Ped Derm 7:126–131, 1990; J Med Genet 15:269–272, 1968 Ring chromosome 13 syndrome - arciform hypopigmentation Rothmund-Thomson syndrome Rozycki syndrome Seckel’s syndrome – abnormal teeth, short stature, hypopigmented papules and macules, small deformed ears lacking lobles, syndactyly, clinodactyly Ped Derm 24:53–56, 2007 17q21.31 microdeletion syndrome Clin Dysmorphol 23:32–34, 2014 Symmetrical progressive leukopathy – Japan and Brazil; punctate leukoderma on shins, extensor arms, abdomen, interscapular areas Ann Dermatol Syphiligr 78:452–454, 1951 Tietz's syndrome – autosomal dominant; absence of pigment(generalized hypopigmentation), deaf-mutism, hypoplastic eyebrows Cutis 73:45–46, 2004; Am J Hum Genet 15:259–264, 1963 Triploidy syndromes Syndromes of the Head and Neck, p. 64, 1990 Tuberous sclerosis - ash leaf macules, confetti hyopigmentation, white eyelashes JAMADerm 151:722–730, 2015; Int J Dermatol 37:911–917, 1998; JAAD 32:915–935, 1995; S Med J 75:227–228, 1982; nevus anemicus and Bier spots in tuberous sclerosis JAMADerm 152:217–218, 2016 Vici syndrome – agenesis of corpus callosum, cleft lip, cutaneous hypopigmentation, cataracts Am J Med Genet 66:378–398, 1996 Vogt-Koyanagi-Harada syndrome - occurs primarily in Asians, blacks, and darkly pigmented Caucasians; Stage 1 - aseptic meningitis; Stage 2 - uveitis(iritis, iridocyclitis) and dysacusis(tinnitus, hearing loss); Stage 3 - depigmentation of skin(60% of patients), depigmentation of hair(poliosis - eyelashes, eyebrows, scalp, and body hair - 90% of patients), alopecia areata; halo nevi Ann DV 127:282–284, 2000; AD 88:146–149, 1980; hypopigmented patches of lower back Ped Derm 29:191–194, 2012 Waardenburg syndrome type 2 – oculocutaneous albinism, sensorineural deafness Clin Dermatol 37:561–579, 2019; Dermatol Online J Nov 15, 2011; Am J Med Genet 6:99–100, 1980

TOXINS Chronic arsenic exposure - macular raindrop hypopigmentation JAAD 80:1215–1231, 2019; JAAD 38:179–185, 1998 Phenol

TRAUMA Burns Cardioversion(defibrillation) – hypopigmented, atrophic, telangiectatic, crusted erythematous plaque of back with rim of hyperpigmentation; delayed onset of years AD 145:1411–1414, 2009 Cryotherapy Dermabrasion Laser Localized involutional lipoatrophy – secondary to injection, suction, massage JAAD 58:490–493, 2008 Post-traumatic leukoderma NEJM 360:160–169, 2009 Radiation dermatitis, chronic JAAD 54:28–46, 2006 Traumatic scars Clin Inf Dis 32:63,149, 2001

VASCULAR LESIONS Hereditary benign telangiectasia – punctuate telangiectasias with anemic halos AD 146:98–99, 2010 Nevus anemicus - personal observation Proliferating hemangioma - nascent hemangioma presenting in infancy as vasoconstricted macule; involuting hemangioma

HYPOPLASIA OF DISTAL PHALANGES Ped Derm 6:130–133, 1989

Werner's syndrome Westerhof syndrome – hereditary congenital hypopigmented and hyperpigmented macules BJD 161:1399–1400, 2009; Curr Prob in Derm VII:143–198, 1995; AD 114:931–936, 1978 Woolf syndrome - piebaldism with congenital nerve deafness Arch Otolaryngol 82:244–250, 1965 Xeroderma pigmentosum X-linked hypohidrotic ectodermal dysplasia, mosaicism – V-shaped hypopigmented linear lesions, patchy hypotrichosis, abnormal teeth Ped Derm 24:551–554, 2007 X-linked reticulate pigmentary disorder with systemic manifestations(familial cutaneous amyloidosis)(Partington syndrome II) – X-linked; rare; Xp21-22; boys with generalized reticulated muddy brown pigmentation(dyschromatosis) with silvery hair, hypopigmented corneal dystrophy(dyskeratosis), coarse unruly hair, unswept eyebrows, hypohidrosis, recurrent pneumonia with chronic obstructive disease, clubbing; failure to thrive, female carriers with linear macular nevoid Blascko-esque hyperpigmentation Ped Derm 22:122–126, 2005; Semin Cut Med Surg 16:72–80, 1997; Am J Med Gen 10:65:1981 Ziprkowski-Margolis syndrome – piebald-type hypopigmentation, deaf-mutism, heterochromic irides Textbook of Neonatal Dermatology, p.365, 2001; AD 86:530–539, 1962

AUTOIMMUNE DISEASES Scleroderma

INFECTIONS Leprosy Tuberculosis verrucosa cutis; lupus vulgaris

METABOLIC DISEASES Charcot foot – diabetes mellitus Congenital erythropoietic porphyria – resorption of digits Ped Derm 20:498–501, 2003 Hyperphosphatasia, mental retardation, distinct facial gestalt, hypoplastic terminal phalanges Eur J Med Genet 53:85–88, 2010

PRIMARY CUTANEOUS DISEASES Acrodermatitis continua of Hallopeau Ainhum Genetic Skin Disorders, Second Edition, 2010, pp.379–381

Hypotrichosis with Growth and Mental Retardation 545 Aplasia cutis congenita

Noonan's syndrome

Epidermolysis bullosa - acroosteolysis

Petty-Laxous-Wiedemann progeria Am J Med Genet A 149A:2200– 2205, 2009

SYNDROMES Acroosteolysis (Hajdu-Cheney syndrome) – short stature, bizarreshaped skull, premature loss of teeth, generalized hirsutism, hyperelastic skin, wide nails Birth Defects 10(12)106–123, 1974 Adams-Oliver syndrome – absence of the distal 4th and 5th distal phanlanges with aplasia cutis congenital Ped Derm 25:115–116, 2008 Amniotic band syndrome Genetic Skin Disorders, Second Edition, 2010, pp.381–383; Ped Derm 6:130–133, 1989 Anonychia and hypoplasia of the nails with absence of distal phalanges and foreshortening of affected digits

Progeria – acroosteolysis AD 125:540544, 1989 Pycnodysostosis Presse Med 70:999–1002, 1962 Raine syndrome Am J Med Genet A 161A:3155–3160, 2013 Ritcher-Schinzel /3-C syndrome Springerplus 2:594, 2013 Robinson's disease - nail hypoplasia Winchester syndrome – acroosteolysis J Pediatr 84:701–709, 1974 Yunis-Varon syndrome

TOXINS Fetal hydantoin syndrome

Chondrodysplasia punctata 1, X-linked Coffin-Siris syndrome Am J Med Genet C Semin Med Genet 166C:241–251, 2014

TRAUMA

Cooks syndrome Indian J Hum Genet 20:206–208, 2014

Umbilical artery catheterization(unintentional) – anonychia, hyponychia, and spontaneous amputation of distal phalanges due to ischemic necrosis BJD 157:1299–1301, 2007

DeLange syndrome dup(9p)syndrome Ectrodactyly syndromes Ellis van Creveld syndrome – chondroectodermal dysplasia J Belg Soc Radiol 102:42, 2018 Fryns syndrome Am J Med Genet A 164A:648–654, 2014

HYPOTRICHOSIS WITH  GROWTH AND MENTAL RETARDATION

Goltz’s syndrome

JAAD 59:92–98, 2008

Hajdu-Choney syndrome – acro-osteolysis of distal phalanges Osteoporosis Int 24:2275–2281, 2013

Nicolaides–Baraitser syndrome – congenital hypotrichosis, unusual facies(inverted triangular shaped face, low frontal hairline, mild facial hirsutism, deep set eyes, pointed nasal tip, thin nasal bridge, high arched palate, thick lower lip), interphalangeal swelling, short metacarpals(“drumstick fingers”), growth and mental retardation

Hand, foot, genital syndrome Am Med Genet A 164A:2398–2402, 2014 Hypoglossia-hypodactylia syndrome Incontinentia pigmenti – foreshortened hand Ped Derm 26:83–86, 2009 Laband syndrome Loeys-Dietz syndrome Am J Med Genet A 164A:461–466, 2014

Biotinidase deficiency - more severe neurologic deterioration; eczematoid and xerotic lesions Cardio-facio-cutaneous syndrome

Mabry syndrome J Coll Phys Surg Pak 28:5192–5194, 2018

Coffin-Siris syndrome – coarse face with broad nose, macrostomia, prominent lips

Mammary-digital-nail (MDN)syndrome Eur J Hum Genet 18:662– 667, 2010

Holocarboxylase synthetase deficiency - more severe neurologic deterioration

Mandibuloacral dysplasia – acral poikiloderma over hands and feet, subcutaneous atrophy Am J Med Genet 95:293–295, 2000;

Menkes’ disease – more severe neurologic deterioration; cutis laxa, hypopigmentation, hair structural anomalies

Clin Genet 26:133–138, 1984

Trichorhinophalangeal syndrome – bulbous and pear-shaped nose with notched ala nasi

Melnick-Needles syndrome Case Rep Dent 2016:9685429 Murray—Puretic-Drescher syndrome – gingival fibromatosis with juvenile hyaline fibromatosis; acroosteolysis J Pediatr Surg 2:427–430, 1967

Trichothiodystrophy

ICHTHYOSIFORM ERUPTIONS JAAD 67:1362–1374, 2012; JAAD 63:607–641, 2010

ACQUIRED ICHTHYOSIS JAAD 17:616–620, 1987

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Bone marrow transplant recipient JAAD 35:17–20, 1996 Dermatomyositis JAAD 40:862–865, 1999; JAAD 16:627–628, 1987; JAAD 8:285–308, 1983 Eosinophilic fasciitis JAAD 34:1079–1080, 1996 Fogo selvagem Graft vs. host disease, chronic Bone Marrow Transplant 21:1159– 1161, 1998; acute Ped Derm 24:49–52, 2007; JAAD 35:17–20, 1996 Hyper IgE syndrome JAAD 54:855–865, 2006 Lupus erythematosus, systemic Lupus 13:270–273, 2004; JAAD 40:862–865, 1999; AD 126:829, 1990; acquired ichthyosis vulgaris associated with systemic lupus vulgaris Cutis 81:159–162, 2008; SLE-progressive systemic sclerosis overlap syndrome Ped Derm 27:170–173, 2010 Mixed connective tissue disease JAAD 40:862–865, 1999; Ann Med Interne 140:221–222, 1989 NEMO deficiency (X-chromosomal ectodermal dysplasia with immunodeficiency) BJD 178:335–349, 2018 Pemphigus foliaceus

CONGENITAL DISORDERS Collodion baby (lamellar exfoliation of the newborn) JAAD 67:1362– 1374, 2012; BJD 163:201–204, 2010; Ped Derm 23:251–254, 2006; Ann Dermatol Syphiligr 3:149–15, 1884; mutations in ABCA1, ALOXE3, ALOX12B, TGM1, and ichthyin  Acral self-healing collodion baby – TGM1 mutation; reverts to normal JAAD 67:233–239, 2012; 161:456–463, 2009; BJD 168:1364–1367, 2013  Anhidrotic ectodermal dysplasia (X-linked) Ped Derm 23:251– 254, 2006; Ann DV 119:821–823, 1992  ARC syndrome – generalized scaling with sparing of skin folds; arthrogryposis, renal tubular degeneration, intrahepatic bile duct hypoplasia, cholestasis, metabolic acidosis, abnormal platelet function, brain malformation; VPS33B JAAD 67:1362–1374, 2012  Autosomal recessive congenital ichthyosis with ichythyin mutation – may have congenital ichthyosiform erythroderma Exp Dermatol 17:373–382, 2008; J Med Genet 44:615–620, 2007; Hum Mol Genet 13:2473–2482, 2004   Asymmetric crying facies Ped Derm 20:134–136, 2003  Bathing suit ichthyosis – autosomal recessive; large plate-like scales, mainly truncal; temperature-sensitive variants in transglutaminase 1 mutation Ped Derm 37:165–170, 2020; JAMADerm 153:537–543, 2017; BJD 168:1364–1367, 2013; AD 148:1191–1195, 2012; JAAD 63:607–641, 2010; AD 148:1191–1195, 2012  Collodion baby, ichthyosiform erythroderma, episodic pustular psoriasis AD 144:351–356, 2008; J Eur Acad DV 16:472–475, 2002; Cutis 37:162–164, 1986

 Congenital bullous ichthyosiform erythroderma Ped Derm 20:25–27, 2003  Congenital erosive and vesicular dermatosis with reticulated scarring – vesicles of the trunk and extremities, erosions, ulcers, erythroderma, collodion baby, ectropion, reticulated soft scarring, scarring alopecia, absent eyebrows, hypohidrosis with compensatory hyperhidrosis Ped Derm 29:756–758, 2012; JAAD 45:946– 948, 2001; Ped Derm 15:214–218, 1998; JAAD 32:873–877, 1995; AD 121:361–367, 1985; most infants premature; extensive symmetrical erosions with scattered vesicles; scarring with hypohidrosis, patchy alopecia, hypoplastic nails Ped Derm 30:387–388, 2013; JAAD 58:S104–106, 2008; JAAD 32:873–7, 1995; AD 126:544–546, 1990; JAAD 17:369–376, 1987; AD 121:361–367, 1985  Congenital hypothyroidism – periorbital puffing; DUOX2, PAX8, SLC5A5, TG, TPO, TSHB, TSHR JAAD 67:1362–1374, 2012; J Pediatr Endocrinol Metab 11:69–73, 1998  Conradi-Hunermann-Happle disease – EBP JAAD 67:1362– 1374, 2012; Ped Derm 20:25–27, 2003  CRIE syndrome – congenital reticulated ichthyosiform erythroderma – formerly ichthyosis en confetti (includes ichthyosis variegate, MAUIE syndrome); minor criteria include collodion membrane, nail dystrophy, large lunulae, palmoplantar hyperkeratosis, ectropion, strabismus, nystagmus, joint contractures, small weight and length; decreased finger length, decreased eyebrows and eyelashes JAMADerm 151:64–69, 2015; JAMADerm 151:15–16, 2015; Acta DV 94:579–582, 2014; Dermatology 188:40–45, 1994   Epidermolytic ichthyosis JAAD 67:1362–1374, 2012  Gaucher’s disease type II – congenital ichthyosiform erythroderma, hepatosplenomegaly, progressive neurologic deterioration; deficiency of beta-glucosidase; GBA JAAD 67:1362–1374, 2012; Ped Derm 20:25–27, 2003; Arch Dis Child Fetal Neonatal Ed 82:F163–166, 2000; Arch Dis Child 63:854–856, 1988   Hay-Wells syndrome Ped Derm 20:25–27, 2003  Holocarboxylase synthetase deficiency – poor feeding, lethargy, hypotonia, respiratory distress, metabolic acidosis, hyperammonemia, organic aciduria, metabolic encephalopathy HLCS JAAD 67:1362–1374, 2012  Hypohidrotic ectodermal dysplasias – EDA, EDAR, EDARADD JAAD 67:1362–1374, 2012   Ichthyosis en confetti JAMADerm 151:64–69, 2015  Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked; mild collodion membrane and erythema at birth; ichthyosis, spiny (keratotic) follicular papules (generalized follicular keratoses), red cheeks, congenital atrichia, non-scarring alopecia, keratotic papules of elbows, knees, fingers, extensor surfaces, xerosis; punctate keratitis, photophobia; nail dystrophy, psychomotor delay, short stature; enamel dysplasia, beefy red tongue and gingiva, angular stomatitis, atopy, lamellar scales, psoriasiform plaques, palmoplantar erythema; skeletal abnormalities, inguinal hernias, cryptorchidism, seizures, atopy, respiratory and cutaneous infections; mutation in MBTPS2 (membrane-­ bound transcription factor peptidase site 2) JAAD 64:716–722, 2011; BJD 163:886–889, 2010; JAAD 63:607–641, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; BJD 142:157–162, 2000; Am J Med Genet 85:365–368, 1999; Ped Derm 12:195, 1995; AD 125:103–106, 1989; Dermatologica 177:341–347, 1988   Ichthyosis vulgaris  Keratitis ichthyosis deafness (KID) syndrome – GJB2 (GJB6) JAAD 67:1362–1374, 2012  KLICK syndrome – congenital ichthyosis, linear keratosis in skin folds, sclerosing palmoplantar keratoderma; POMP JAAD 67:1362–1374, 2012; JAAD 63:607–641, 2010; Acta DV 77:225–227, 1997 546

Ichthyosiform Eruptions  Koraxitrachitic syndrome – self-healing collodion baby with residual mottled reticulated atrophy (dappled atrophy of dermis); alopecia, absent eyelashes and eyebrows, conjunctival pannus, hypertelorism, prominent nasal root, large mouth, micrognathia, brachydactyly, syndactyly of interdigital spaces Am J Med Genet 86:454–458, 1999  Lamellar ichthyosis – autosomal recessive, dominant; TGM1, ABCA12, ALOX12B, BIPAL4 mutations  Loricrin keratoderma – autosomal dominant; congenital ichthyosiform erythroderma and collodion baby; honeycomb ichthyosis – LOR BJD 172:162–164, 2015; JAAD 63:607–641, 2010; BJD 145:657–660, 2001  Mutation of ALOX12B – autosomal recessive; severe collodion phenotype BJD 173:285–287, 2015  Neonatal ichthyosis-sclerosing cholangitis syndrome – autosomal recessive; lamellar ichthyosis, scalp hypotrichosis, scarring alopecia, sclerosing cholangitis; congenital paucity of bile ducts; oligodontia, hypodontia, dysplastic enamel; mutation in CLDN1 (claudin-1; a tight junction component) BJD 163:205–207, 2010  Neutral lipid storage disease – ABHD5 JAAD 67:1362–1374, 2012   Non-bullous congenital ichthyosiform erythroderma   Netherton’s syndrome  Palmoplantar keratoderma with anogenital leukokeratosis JAAD 67:1362–1374, 2012   Sjogren-Larsson syndrome  Self-healing collodion baby (lamellar ichthyosis of the newborn) – reverts to normal; TGM1, ALOX12B, ALOXE3 BJD 168:1364– 1367, 2013; AD 105:394–399, 1972   Palmoplantar keratoderma J Med Assoc Thai 76:17–22, 1993  Trichothiodystrophy with ichthyosis – ERCC2/XPD, ERCC3/XPB, GTF2H5/TTDA, C7Orf11/TTDN1 JAAD 67:1362–1374, 2012   X-linked recessive ichthyosis JAAD 67:1362–1374, 2012  Differential diagnosis of collodion baby JAAD 67:1362–1374, 2012   Ichthyosis prematurity syndrome – red swollen skin covered with greasy thick vernix caseosa-like scale in premature infant; neonatal asphyxia; rapidly improves and develops chronic ichthyosis with severe pruritus, eosinophilia and atopy; decreased incorporation of very long chain fatty acids into cellular lipids; impaired skin barrier function; SLC27A4 JAAD 67:1362–1374, 2012    Harlequin ichthyosis – ABCA12    Netherton’s syndrome – SPINK5    Sjogren-Larsson syndrome – ALDH3A2  Ichthyosis prematurity syndrome (“self-healing congenital verruciform hyperkeratosis”) – autosomal recessive; premature birth, ichthyosis, erythrodermic infant with caseous vernix-like desquamation neonatal asphyxia; hyperkeratotic thick caseous lesions of hands, feet, and scalp; eosinophilia; Norway and Sweden; evolves into generalized xerosis and mild flexural hyperkeratosis and of lower back; cutaneous cobblestoning; keratosis pilaris-like changes; fine desquamation of ankles; focal erythema, diffuse alopecia, fine scaling of the scalp, red and white dermatographism; in utero polyhydramnios with premature birth, thick caseous desquamating skin (thick vernix caseosa-like covering) (hyperkeratotic scalp) neonatal asphyxia; later in childhood, dry skin with follicular keratosis; mutation in fatty acid transporter protein 4 (FATP4) Ped Derm 31:517–518, 2014; JAAD 66:606–616, 2012; AD 147:750–752, 2011; JAAD 63:607–641, 2010; JAAD 59:S71–74, 2008   Ichthyosis vulgaris Ann DV 113:773–785, 1986   IFAP syndrome  Keratitis ichthyosis deafness syndrome – GJD2 (GJB6) mutation JAAD 67:1362–1374, 2012; Ped Derm 20:25–27, 2003

547

 Lamellar ichthyosis – autosomal recessive, dominant; TGM1, ABCA12, ALOX1B, BIPAL4 mutations Ann DV 113:773–785, 1986; mild lamellar ichthyosis Ped Derm 9:95–97, 1992  Netherton’s syndrome – SPINK5 Cureus 10:e3070, 2018; Mod Probl Paediatr 20:40–49, 1978  Neu-Laxova syndrome – severe and lethal serine deficiency; dysmorphic , contractures, webbing of fingers and toes; collodionlike skin J Inher Metabol Dis 40:609–620, 2017; Ped Derm 20:25–27, 2003  Neutral lipid storage disease (Chanarin-Dorfman syndrome) BJD 153:838–841, 2005; Arch Dis Child 77:184, 1997; Dermatologica 177:237–240, 1988  Non-bullous ichthyosiform erythroderma Ann DV 113:773–785, 1986   Restrictive dermopathy Ped Derm 20:25–27, 2003  Sjogren-Larsson syndrome – ALDH3A2 Clin Genet 93:721–730, 2018; Ann DV 113:773–785, 1986  Self-healing (acral self-healing) collodion baby (self-improving collodion ichthyosis) – autosomal recessive Ped Derm 9:95–97, 1992; may be a premature infant; associated with hypoplasia of nasal and/or auricular cartilage; associated with Sjogren-Larsson syndrome, Gaucher’s disease, and trichothiodystrophy BJD 161:456–463, 2009; Soc Ped Derm Annual Meeting, July, 2006; transglutaminase-1 mutation AD 148:1191–1195, 2012; JID 120:224–228, 2003; ALOX12B gene AD 144:351–356, 2008; TGM1 mutations BJD 162:448–451, 2010; ALOXE3 JAAD 63:607–641, 2010  Trichothiodystrophy BJD 106:705–710, 1982   X-linked ichthyosis JAMA 202:485–488, 1967 Congenital ichthyosiform dermatoses associated with blistering or denudation Ped Derm 19:382–387, 2002   Annular epidermolytic hyperkeratosis   Epidermolytic hyperkeratosis   Ichthyosis bullosa of Siemens   Ichthyosis exfoliativa, autosomal dominant   Ichthyosis exfoliativa, autosomal recessive   Peeling skin syndrome

DRUG-INDUCED AD 111:1446–1447, 1975 Allopurinol Azacosterol hydrochloride Benzophenone JAAD 40:862–865, 1999 Cholesterol-lowering drugs Butyrophenone Dixyrazine Nafoxidine Nicotinic acid Arch Int Med 107:639, 1961 Triparanol AD 87:372–377, 1963 Cimetidine AD 118:253–254, 1982; NEJM 299:992–996, 1978 Clofazimine Cutis 29:341–343 1982 Dixyrazine JAAD 40:862–865, 1999; Acta DV (Stockh) 61:85–88, 1981 Hydroxyurea JAAD 49:339–341, 2003; Clin Exp Dermatol 27:8–13, 2002 Immunosuppressive therapy in transplant recipients – diffuse hyperpigmented xerotic dermatitis JAAD 44:932–939, 2001 Isoniazid Lovastatin

548 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Maprotiline Hautarzt 42:455–458, 1991 Niacin JAAD 40:862–865, 1999

dermatitis, alopecia, branny desquamation, and atrophic glossitis Semin Dermatol 10:296–302, 1991; JAAD 9:97–103, 1983

Phenothiazines

Celiac disease Eur J Dermatol 10:398–399, 2000

Ponatinib – pityriasis rubra pilaris-like changes, eyebrow thinning, ichthyosiform changes BJD 173:574–577, 2015

Chanarin-Dorfman disease – autosomal recessive; neutral lipid storage disease; triglyceride-related non-lysosomal storage disease; ABHD5 mutation; which encodes protein of esterase/lipase/ thioesterase subfamily of triglyceride lipase-mediated lipolysis; at birth hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness; generalized scaling, mild erythroderma; resembles congenital ichthyosiform erythroderma; coarse facies, non-bullous congenital ichthyosiform erythroderma; collodion baby or ichthyosiform erythroderma; thereafter pattern resembles non-bullous ichthyosiform erythroderma; erythrokeratodermia variabilis-like presentation; seborrheic dermatitis-like around the face and scalp; hyperkeratosis of the knees; hepatomegaly, ataxia, neurosensory hearing loss, cataracts, nystagmus, short stature, mental retardation, ataxia, myopathy, hepatosplenomegaly; leukocytes with lipid vacuoles JAAD 669:1362–1374, 2012; BJD 158:1378–1380, 2008; Ped Derm 25:326–331, 2008; BJD 153:838–841, 2005; Curr Prob Derm 14:71–116, 2002; BJD 144:430–432, 2001; Clin Exp Dermatol 19:434–437, 1994; Ped Derm 5:173–177, 1988; JAAD 17:801–808, 1987; AD 121:1000–1008, 1985; harlequin fetus Dermatologica 177:237–240, 1988; collodion baby Arch Dis Child 77:184, 1997; renal disease; BJD 176:545–548, 2017; AD 141:798–800, 2005; Am J Dermatopathol 20:79–85, 1998

Retinoids – acitretin, etretinate, and isotretinoin – retinoid dermatitis JAAD 40:862–865, 1999

EXOGENOUS AGENTS Kava dermopathy due to kava beverage made from kava pepper (Piper methysticum) – pellagra-like ichthyosiform dermatosis JAAD 31:89–97, 1994 Nicotinic acid – personal observation

INFECTIONS AND INFESTATIONS African trypanosomiasis AD 131:1178–1182, 1995 AIDS JAAD 40:862–865, 1999; JAAD 22:1270–1277, 1990; ad 125:357–361, 1989; JAAD 17:951–961, 1987; JAAD 17:210, 1987; Cutis 39:421–423, 1987 Erythrasma HIV-2 JAAD 29:701–708, 1993 HTLV-1 – acquired ichthyosis and associated myelopathy BJD 149:776–781, 2003; JAAD 17(pt1)210–220, 1987 Leprosy – lepromatous leprosy JAAD 40:862–865, 1999; BJD 77:151–157, 1965; borderline tuberculoid Mycobacterium tuberculosis JAAD 40:862–865, 1999 Onchocerciasis – acquired ichthyosis with atrophic changes earliest of buttock, shoulders, and legs; fine wrinkling and xerotic skin (lizard skin) BJD 121:187–198, 1989 Scabies, crusted (Norwegian scabies) JAMA 313:298–299, 2015 Scarlet fever – exfoliation Staphylococcal scalded skin syndrome Tinea corporis (generalized dermatophytosis) – Trichophyton tonsurans AD 129:1184–1194, 1993 Tinea versicolor

INFLAMMATORY DISORDERS Eosinophilic fasciitis – acquired ichthyosis JAAD 34:1079–1080, 1996 Sarcoid JAMADerm 156:809–810, 2020; Cutis 102:408–410, 2018; JAAD 40:862–865, 1999; JAAD 17:616–620, 1987; AD 114:100– 101, 1978

METABOLIC Anorexia nervosa – xerosis; flaky paint scaling JAAD 21:1–30, 1989 Biotin deficiency – xerosis; flaky paint scaling JAAD 15:1263–1274, 1986 Biotinidase deficiency – neonatal and infantile; early resemble ichthyosiform eruption; both are autosomal recessive; neonatal – holocarboxylase synthetase deficient; first 6 weeks of life; fiery red intertriginous dermatitis; infantile – biotinidase deficient; early, ichthyosiform eruption; after 3 months of life, intertriginous rash with keratoconjunctivitis, xerosis, generalized pallor, periorificial

Diabetes mellitus – migratory ichthyosiform dermatosis (polycyclic ichthyosiform rash) with type 2 diabetes mellitus and insulin resistance AD 135:1237–1242, 1999; Diabetes Care 21:1032, 1998 Essential fatty acid deficiency – xerosis JAAD 21:1–30, 1989; JID 7:230–233, 1980 Gaucher’s disease, type 2 – autosomal recessive; collodion baby, mild scaling later; congenital ichthyosiform erythroderma, hepatosplenomegaly, progressive neurological deterioration, deficiency of beta-­glucosidase JAAD 67:1362–1374, 2012; Curr Prob Derm 14:71–116, 2002; Arch Dis Child Fetal Neonatal Ed 82::F163–166, 2000; Arch Dis Child 66:667, 1991; congenital ichthyosis with restrictive dermopathy Obstet Gynecol 81:842–844, 1993 Hemochromatosis – ichthyosis-like atrophic dry skin J Drugs in Dermatol 9:719–722, 2010; Clev Clin J Med 76:599–606, 2009; AD 113:161–165, 1977; Medicine 34:381–430, 1955 Holocarboxylase synthetase deficiency – autosomal recessive; holocarboxylase synthetase catalyzes transfer of biotin to four biotin-dependent enzymes: (1) 3-methylcrotonyl CoA carboxylase, (2) propionyl CoA carboxylase, (3) pyruvate carboxylase, and (4) acetyl CoA carboxylase JAAD 67:1362–1374, 2012; Ped Derm 23:142–144, 2006 Hyperparathyroidism JAAD 40:862–865, 1999; JAAD 21:801–802, 1989 Hypopituitarism JAAD 40:862–865, 1999; BJD 97:327–334, 1977 Hypothyroidism (myxedema) – periorbital puffiness JAAD 67:1362–1374, 2012 Ped Derm 22:447–449, 2005; JAAD 40:862–865, 1999 Ichthyosiform erythroderma (lamellar ichthyosis or non-bullous congenital ichthyosiform erythroderma) – development of rickets BJD 158:603–606, 2008 Kwashiorkor – xerosis; begins as red-purple-brown patches which heal as flaky paint scaling Cutis 67:321–327, 2001; JAAD 21:1–30, 1989; Indian J Med Sci 43:92–94, 1989; in elderly, cracked skin on lower abdomen and pretibial areas (geriatric nutritional eczema) Liver disease, chronic cirrhosis – zinc deficiency; generalized dermatitis of erythema craquele (crackled and reticulated dermati-

Ichthyosiform Eruptions 549 tis) with perianal and perigenital erosions and crusts; cheilitis, hair loss; Ann DV 114:39–53, 1987 Malabsorption syndromes (celiac disease, pancreatic insufficiency) JAAD 40:862–865, 1999 Malnutrition Hautarzt 46:836–840, 1995 Marasmus – xerosis JAAD 21:1–30, 1989 Methylmalonic acidemia – deficiency of methylmalonyl coenzyme A mutase or its cofactors adenosylcobalamin (vitamin B12) and methylcobalamin; affects metabolism of four amino acids (valine, isoleucine, threonine, methionine); these patients fed low-protein diets limited in branched chain amino acids Ped Derm 24:455–456, 2007; Dermatol Pediatr Lat 1:46–48, 2003; Ped Derm 16:95–102, 1999; AD 133:1563–1566, 1997; J Pediatr 124:416–420, 1994; BJD 131:93–98, 1994 Multiple nutritional deficiencies – personal observation Multiple sulfatase deficiency – autosomal recessive; broad thumbs, mild ichthyosis, gargoylism, mental retardation, mucopolysaccharidosis BJD 147:353–355, 2002; Ped Derm 18:388–392, 2001; Ped Derm 14:369–372, 1997 Pellagra (niacin deficiency) – red pigmented sharply marginated, photodistributed rash, including drug-induced pellagra-like dermatitis – 6-mercaptopurine, 5-fluorouracil, INH (all of the above – also seborrheic dermatitis-like); resembles Hartnup disease Cutis 68:31–34, 2001; JAAD 40:862–865, 1999; Ped Derm 16:95–102, 1999 Phrynoderma (vitamin A deficiency) – xerosis JAAD 40:862–865, 1999; JAAD 21:1–30, 1989

Lymphoma – Hodgkin’s disease – ichthyosis vulgaris-like changes of legs or generalized (increased G-CSF levels) JAAD 49:772–773, 2003; Br Med J 1:763–764, 1955; non-Hodgkin’s lymphoma, reticulolymphosarcoma, cutaneous T-cell lymphoma (CTCL) BJD 161:115–120, 2009; JAAD 34:887–889, 1996; B-cell lymphomas JAAD 40:862–865, 1999; CD 30+ cutaneous anaplastic large cell lymphoma BJD 161:115–120, 2009; JAAD 42:914–920, 2000; Tumori 85:71–74, 1999 Lymphomatoid papulosis JAAD 30:889–892, 1994; AD 122:1400– 1405, 1986 Metastatic male breast carcinoma – sclerodermoid ichthyosiform plaque of the chest wall AD 139:1497–1502, 2003 Pityriasis rotunda – mutation in profilaggrin N-terminal domain BJD 166:227–229, 2012; may be paraneoplastic or with leprosy JAAD 31:866–871, 1994; JAAD 14:74–78, 1986; BJD 76:223–227, 1964 Polycythemia rubra vera JAAD 40:862–865, 1999 Rhabdomyosarcoma JAAD 40:862–865, 1999 Spindle cell sarcoma JAAD 40:862–865, 1999

PHOTOSENSITIVE DISEASES Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelinationss, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria, and mental and physical retardation JAAD 67:1362– 1374, 2012; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997

Renal disease JAAD 40:862–865, 1999 Vitamin A excess Zinc deficiency JAAD 40:862–865, 1999

PRIMARY CUTANEOUS DISEASES Adolescent-onset ichthyosiform erythroderma BJD 144:1063–1066, 2001

NEOPLASTIC Epidermal nevus JAAD 63:607–641, 2010 Kaposi’s sarcoma JAAD 40:862–865, 1999 Leukemia – HTLV-1 leukemia/lymphoma – personal observation Lymphoma – Hodgkin’s disease JAAD 65:465–467, 2011; ichthyosiform cutaneous T-cell lymphoma JAMADerm 155:1185–1186, 2019; JAAD 50:368–374, 2004; JAAD 34:887–889, 1996; Int J Derm 23:458–461, 1984; granulomatous slack skin syndrome AD 141:1595–1600, 2005; Ki 1+ large cell lymphoma of the skin J Clin Pathol 44:119–125, 1991

PARANEOPLASTIC DISORDERS Acrokeratosis paraneoplastica – with acquired ichthyosis in Hodgkin’s disease BJD 133:322–325, 1995 Acquired ichthyosis – mostly Hodgkin’s disease and others JAAD 55:647–656, 2006; JAAD 54:745–762, 2006; Arch Dermatol Syphil 47:778–781, 1943; multiple myeloma AD Syphilol 72:506–522, 1955; carcinoma of the breast, lung, and cervix AD 111:1446–1447, 1975; Kaposi’s sarcoma Dermatologica 147:348–351, 1973; carcinoma of the breast, colon, lung, and cervix, intestinal leiomyosarcoma JAAD 40:862–865, 1999; myeloma JAAD 40:862–865, 1999; paraneoplastic ichthyosis and Addisonian hyperpigmentation – associated with multiple myeloma J Coll of Physicians and Surgeons Pakistan 21:40–42, 2011 Leukemia JAAD 40:862–865, 1999; HTLV-1 (acute T-cell leukemia) (adult T-cell lymphoma/leukemia) JAAD 49:979–1000, 2003; JAAD 46:S137–141, 2002

Annular epidermolytic ichthyosis – variant of bullous congenital ichthyosiform erythroderma – autosomal dominant; mutation in keratin 1 or 10 JAAD 63:607–641, 2010; BJD 141:642–646, 1999; JID 111:1220–1223, 1998; JAAD 27:348–355, 1992 Arthrogryposis, renal tubular dysfunction, and cholestasis (ARC) syndrome – ichthyosis, scarring alopecia, ectropion, arthrogryposis of the wrist, knee, and hip Ped Derm 22:539–542, 2005 Asteatotic dermatitis (erythema craquele) Autosomal recessive congenital ichthyosis – variable erythroderma; dark plate-like lamellar or small pale scale; palmoplantar keratoderma BJD 163:201–204, 2010; Hum Mut 31:1090–1096, 2010  Mutations:   TGM1 – transglutaminase 1 enzyme    ALOXE3, ALOX12B – proteins eLOX3, 12R-LOX; part of the lipoxygenase family that synthesizes epoxy alcohol responsible for activating PPAR-alpha promoting epidermal differentiation; autosomal recessive; severe collodion phenotype BJD 173:285–287, 2015    ABCA12 – ATP-binding cassette subfamily A12; transports lipids from lamellar granules to the stratum corneum    PNPLA1 – palatin-like phospholipase domain containing protein A; critical to lipid homeostasis of the skin   Bathing suit ichthyosis – autosomal recessive congenital ichthyosis (ARCI) – generalized dark brown plate-like scales, spares medial cheeks and forearms Ped Derm 37:165–170, 2020    CYP4F22 – cytochrome P450 protein autosomal recessive congenital ichthyosis – ichthyosis, erythroderma, collodion baby, contractures of large joints, palmoplantar hyperlinearity, edema of fingers; CYP4F22 mutation JAMADerm 154:1320– 1323, 2019; BJD 176:1068–1073m 2017NIPAL4 – i

550 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Autosomal recessive congenital ichthyosis with ichythyin mutation – light pink erythema with fine white scale and mild palmoplantar keratoderma; collodion baby Exp Dermatol 17:373–382, 2008; J Med Genet 44:615–620, 2007; Hum Mol Genet 13:2473–2482, 2004

rippled hyperkeratosis of extremities, lower trunk, flexures; peeling; hypertrichosis; circumscribed patchy scaling (mauserung); palmoplantar blistering with hyperhidrosis Ped Derm 30:469–472, 2013; Curr Prob Derm 14:71–116, 2002; BJD 140:689–695, 1999; JID 103:277–281, 1994; JAAD 14:1000–1005, 1986

Autosomal recessive epidermolytic hyperkeratosis – KRT10 JAAD 63:607–641, 2010

Ichthyosis, cerebellar degeneration, and hepatosplenomegaly BJD 100:585–590, 1979

Autosomal recessive exfoliative ichthyosis – congenital erythroderma, diffuse hyperkeratosis, palmoplantar keratoderma, palmoplantar peeling, hyperhidrosis, erosions; mutation in cysteine protease inhibitor A (cystatin A) BJD 172:1628–1632, 2015

Ichthyosis congenita, type IV – resembles diffuse cutaneous mastocytosis BJD 136:377–379, 1997

Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) – autosomal dominant; warty hyperkeratosis; palmoplantar keratoderma Curr Prob Derm 14:71–116, 2002 Confluent and reticulated papillomatosis of Gougerot and Carteaud – ichthyosiform lesions of forehead Cutis 78:239–240, 2006; JAAD 49:1182–1184, 2003; BJD 142:1252–1253, 2000; AD 132:1400– 1401, 1996; BJD 129:351–353, 1993; Bull Soc Fr Dermatol Syphilol 34:719–721, 1927 Congenital ichthyosiform erythroderma (autosomal recessive congenital ichthyosis) – with collodion membrane; autosomal recessive; ALOX12B mutation (lipoxygenase) BJD 163:201–204, 2010 Ichthyosis en confetti (congenital reticulated ichthyosiform erythroderma) – reticulated erythroderma with guttate hypopigmentation, palmoplantar keratoderma; loss of dermatoglyphics; temporary hypertrichosis of the normal skin BJD 166:434–439, 2012; JAAD 63:607–641, 2010 Cyclic ichthyosis with epidermolytic hyperkeratosis Am J Hum Genet 64: 732–738, 1999 Darier’s disease Epidermolytic ichthyosis (formerly epidermolytic hyperkeratosis) BJD 164:442–447, 2011; AD 130:1026–1035, 1994; palmoplantar keratoderma and mild fine scaling in body folds; mutation in L12 domain of keratin 1 BJD 162:875–879, 2010 Erythrokeratodermia hiemalis Erythrokeratodermia variabilis – GJB3/GJB4 JAAD 63:607–641, 2010; Erythrokeratodermia with ataxia Exfoliation of the newborn Fine scaling, keratosis pilaris, periorificial crusting, palmoplantar hyperkeratosis, blistering JAAD 34:379–385, 1996 Follicular ichthyosis BJD 111:101–109, 1984 Harlequin fetus (harlequin ichthyosis) (ichthyosis congenital fetalis) – autosomal recessive; rigid plates; severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis; mutation in ABCA 12 (adenosine triphosphate-binding cassette A12); keratinocyte lipid transfer associated with lamellar granule formation and lipid transfer via lamellar granules on the surface of keratinocytes Ped Derm 36:339–341, 2019; Ped Derm 31:539–546, 2014; Ped Derm 26:575–578, 2009; BJD 158:611–613, 2008; BJD 155:204–206, 2006; AD 142:914–918, 2006; BJD 153:811–814, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982; constrictions Ped Derm 31:625–629, 2014 Ichthyosiform dermatosis with superficial blister formation and peeling JAAD 34:379–385, 1996 Ichthyosiform erythroderma with generalized pustulosis BJD 138:502–505, 1998 Ichthyosis bullosa of Siemens (superficial epidermolytic ichthyosis) – autosomal dominant; mutation of keratin 2e; superficial blistering of flexures, shins, abdomen with annular peeling; gray,

Ichthyosis and deafness Ped Derm 31:276–280, 2014 Ichthyosis en confetti (congenital reticulated ichthyosiform erythroderma) – reticulated erythroderma with guttate hypopigmentation, palmoplantar keratoderma; loss of dermatoglyphics; temporary hypertrichosis of the normal skin; elongated nails with large lunulae, microtia, joint contractures, neurologic defects; breast hypoplasia; collodion baby, ectropion, strabismus, nystagmus; keratin 10 mutations JAMADerm 151:64–69, 2015; BJD 166:434–439, 2012; neonatal ichthyosiform erythroderma, hyperpigmented verrucous, and cerebriform plaques of the heels and neck BJD 176:249–251, 2017 Ichthyosis exfoliativa – autosomal recessive; peeling of neonate; resembles ichthyosis bullosa of Siemens in adult life BJD 149:174– 180, 2003; thought to be identical to ichthyosis bullosa of Siemens JAAD 27:348–355, 1992; BJD 124:191–194, 1991 Ichthyosis follicularis with atrichia and photophobia – mutation in MBTPS2 Clin Exp Dermatol 45:505–507, 2020 Ichthyosis hystrix (Curth-Macklin) – autosomal dominant; spiky hyperkeratosis; epidermolytic hyperkeratosis with diffuse or striate PPK; KRT1 mutation JAAD 63:607–641, 2010; Curr Prob Derm 14:71–116, 2002 Ichthyosis hystrix, Lambert type – widespread hyperpigmented hyperkeratotic confluent plaques of the trunk and extremities BJD 156:1027–1031, 2007; Am Hum Genet 6:371–382, 1954 Ichthyosis with renal disease – red skin, fine scale, vesicles over dorsal hands and feet, aminoaciduria, dwarfism, mental retardation J Pediatr 82:466–470, 1973 Ichthyosis, mental retardation, dwarfism, and renal impairment J Pediatr 92:766–768, 1978 Ichthyosis, split hairs, aminoaciduria Ichthyosis variegata (congenital reticular ichthyosiform erythroderma) BJD 139:893–896, 1998 Ichthyosis vulgaris – autosomal dominant; fine white scale; filaggrin mutations BJD 168:1155–1166, 2013; BJD 160:771–781, 2009; Curr Prob Derm 14:71–116, 2002 Ichthyosis vulgaris-like with keratoderma and increased serum beta-glucuronidase Dermatologica 177:341–347, 1988 Ichthyosis vulgaris-like – autosomal recessive; no collodion membrane AD 122:428–433, 1986 Ichthyosis vulgaris palmaris et plantaris dominans Dermatologica 165:627–635, 1982 Lamellar ichthyosis – autosomal recessive JAAD 67:1362–1374, 2012; Ped Derm 28:451–455, 2011; autosomal dominant Clin Genet 30:122–126, 1986; Clin Genet 26:457–461, 1984; mutations in TGM1, ABCA12, FLJ39501 AD 144:342–346, 2008; bathing suit ichthyosis distribution; TGM1 mutations BJD 162:448–451, 2010 Loricrin keratoderma – autosomal dominant; ichthyosis, honeycombed palmoplantar keratoderma, pseudoainhum BJD 172:1158– 1162, 2015; BJD 159:714–719, 2008; Ped Derm 19:285–292, 2002 Mal de Meleda – autosomal dominant, autosomal recessive; diffuse PPK; progressive and transgrediens with acral erythema in

Ichthyosiform Eruptions

551

glove-like distribution; perioral erythema and hyperkeratosis; hyperkeratotic plaques over joints, malodorous hyperhidrosis; ichthyosis; knuckle pads; pseudoainhum with amputation; lingua plicata, brachydactyly, syndactyly, hairy palms and soles, nail anomalies, lichenoid plaques, high-arched palate, left-handedness; mild ichthyosis; mutations in ARS component B gene (SLURP1) BJD 168:1372–1374, 2013; AD 147:748–750, 2011; BJD 160:160:878–880, 2009; AD 144:375–379, 2008; JID 120:351–355, 2003; Dermatology 203:7–13, 2001; AD 136:1247–1252, 2000; J Dermatol 27:664–668, 2000; BJD 128:207–212, 1993; Dermatologica 171:30–37, 1985; Arch Dermatol Syphilol 42:163– 174, 1898

Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC syndrome) – collodion baby J Dermatol 46:422–425, 2019

Morphea – acquired ichthyosis Ped Derm 27:170–173, 2010

Atypical ichthyosis vulgaris with hypogonadism

Naxos syndrome – personal observation

Bazex-Dupre-Christol-like syndrome – X-linked dominant; basal cell carcinomas which resemble nevi or comedones, hypohidrosis, hypotrichosis, congenital alopecia of the scalp and eyebrows, milia, follicular atrophoderma with ice pick marks of dorsal hands, feet extensor elbows, knees, and face; atopy, comedo-like papules, keratosis pilaris, ichthyosis, anhidrosis; arachnodactyly with joint hyperlaxity, osteochondritis, deafness, leukemia, lingua plicata; UBE 2A gene Int J Dermatol 57:1102–1106, 2018; Ped Derm 23:286– 290, 2006; Derm Surg 26:152–154, 2000; Ped Derm 16:108–110, 1999; AD 130:337–342, 1994; Ann Dermatol Syphiligr 93:241–254, 1966; Bull Soc Dermatol Syphiligr 71:206, 1964

Non-bullous CIE (congenital ichthyosiform erythroderma) (erythrodermic lamellar ichthyosis) – autosomal recessive; collodion baby; fine white scales, background erythema; mutations in TGM1, CG158, ichthyin, ALOXE3 (lipoxygenase-3), ALOX12B (12(R) lipoxygenase-3) AD 144:342–346, 2008; Curr Prob Derm 14:71–116, 2002; AD 121:477–488, 1985; congenital erythroderma with subsequent generalized scaling BJD 158:1125–1128, 2008 Peeling skin syndrome – autosomal recessive JAAD 63:607–641, 2010 Pityriasis rubra pilaris – personal observation Progressive symmetric erythrokeratodermia Superficial epidermolytic hyperkeratosis – KRT2 mutation JAAD 63:607–641, 2010 X-linked recessive ichthyosis (steroid sulfatase deficiency) – in infancy, scaling of extensor arms and sides of the trunk; then flexural scaling and of legs; large dark scaling of extensor surfaces of outer arms, outer thighs, around lower legs; flexures may be involved; decreased numbers of sweat glands BJD 179:933–939, 2018; JAAD 72:617–627, 2015; JAAD 62:480–485, 2010; Curr Prob Derm 14:71–116, 2002; Br Med J 1:947–950, 1966; AD 92:1–6, 1965; combination of mucopolysaccharidosis type 2 (aryl sulfatase B deficiency), metachromatic leukodystrophy (aryl sulfatase A deficiency), and XLRI Ped Derm 14:369–372, 1997; Clin Genet 30:409–415, 1986   Associations with X-linked ichthyosis:    Congenital defect of abdominal wall   Crigler-Najjar syndrome   Leri-Weill dyschondrosteosis    Acute lymphoblastic leukemia    Nephrotic syndrome and renal agenesis    Neurofibromatosis type 1   Poland syndrome    Primary microcephaly due to ASPM mutation   Pyloric hypertrophy    Seizures and central nervous system abnormalities (ADHD)    Testicular carcinoma X-linked recessive ichthyosis without steroid sulfatase deficiency Am J Med Genet 59:143–148, 1995

SYNDROMES Ablepharon with follicular ichthyosis and hairy pinnae Clin Genet 2:111–114, 1971 Adolescent-onset ichthyosiform-like erythroderma with lichenoid tissue reaction BJD 144:1063–1066, 2001 Anhidrotic ectodermal dysplasia

Arthrogryposis, renal tubular dysfunction, cholestasis, ichthyosis syndrome (ARCI) (ARC syndrome) – severe lamellar ichthyosis, arthrogryposis (contractures of limbs), renal dysfunctions, cholestasis, dysmorphism, recurrent infections, abnormal platelet function, failure to thrive, nephrogenic diabetes insipidus, neurogenic muscular atrophy, absent corpus callosum, nerve deafness; loss of function mutation VPS33B; defective lamellar granule secretion JAAD 63:607–641, 2010; J Pediatr Gastroenterol Nutr 48:348–354, 2009; AD 144:334–340, 2008; Nat Genet 36:400–404, 2004; Dur J Pediatr 156:78, 1997

Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; translucent skin-colored papules (non-caseating granulomas) of trunk and extremities; may resolve with pitted scars with follicular atrophoderma; ichthyosiform changes; with uveitis, synovitis, arthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints) mutations in NOD2 (nucleotide-binding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996 Buschke-Ollendorff syndrome Sybert’s Genetic Skin Disorders Cardio-facio-cutaneous syndrome (Noonan-like short stature syndrome) – xerosis/ichthyosis, eczematous dermatitis, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, nevi, keratosis pilaris, autosomal dominant, patchy, or widespread ichthyosiform eruption, sparse curly short scalp hair and eyebrows and lashes, hemangiomas, acanthosis nigricans, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects JAAD 46:161–183, 2002; Ped Derm 17:231–234, 2000; JAAD 28:815– 819, 1993; AD 129:46–47, 1993; port wine stain Clin Genet 42:206–209, 1992; JAAD 22:920–922, 1990 CEDNIK syndrome (cerebral dysgenesis-neuropathy-ichthyosis-­ keratoderma) – microcephaly; dysmorphic face with small anterior fontanelles; pointed prominent nasal tip, small chin, inverted nipples and long toes, high palate, thick gingivae, cradle cap, sparse brittle coarse hair, scarring alopecia, fixed flexion posture; decreased SNAP 29 protein; mutation in SNARE proteins mediating vesicle trafficking; mutation in ABCA12 gene Ped Derm 36:372–376, 2019; BJD 164:610–616, 2011; AD 144:334–340, 2008 Cerebral dysgenesis-neuropathy-ichthyosis-palmoplantar keratoderma syndrome JAAD 63:607–641, 2010; Am J Hum Genet 77:242–251, 2005 Chanarin-Dorfman syndrome (neutral lipid storage disease) – autosomal recessive; non-bullous congenital ichthyosiform erythroderma, ichthyosis with mild erythema and scale; hyperkeratosis of the palms and soles, ichthyosiform eruption, lipid vacuoles within neutrophils, liver, muscle, and CNS involvement; hepatomegaly and developmental delay; Jordan’s anomaly (lipid vacuoles in leukocytes); mutation in ABHD5/Cgi-58 gene – encodes crucial cofactor

552 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 for adipose triglyceride lipase Ped Derm 31:612–614, 2014; BJD 164:1390–1392, 2011; Ped Derm 26:40–43, 2009; BJD 144:430– 432, 2001; erythrokeratodermia variabilis-­like ichthyosis BJD 153:838–841, 2005; renal disease BJD 176:545–548, 2017 Chondrodysplasia punctata, X-linked recessive – short stature with ichthyosis Ped Derm 18:442–444, 2001 Congenital ichthyosis, alopecia, eclabion, ectropion, mental retardation – autosomal recessive Clin Genet 31:102–108, 1987 Congenital ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis Am J Med Geneet 13:186–189, 1998 Congenital ichthyosis with linear keratotic flexural papules and mutilating sclerosing palmoplantar keratoderma AD 125:103–106, 1989 Conradi-Hunermann syndrome (chondrodysplasia punctata – X-linked dominant) – linear and whorled hyperkeratosis, follicular atrophoderma of forearms in Blaschko distribution; linear atrophic lesions with follicular plugging of scalp; cicatricial alopecia of scalp; patchy-patterned alopecia, generalized xerosis; cataracts, chondrodysplasia punctata; asymmetric shortening of long bones, epiphyseal stippling, short stature, short limbs, kyphoscoliosis, craniofacial abnormalities) short arms and legs; cataracts; X-linked; mutation in emopamil-binding protein (EBP) Ped Derm 31:493–496, 2014; BJD 160:1335–1337, 2009; Curr Prob in Derm VII:143–198, 1995; AD 121:1064–1065, 1985; ichthyotic and psoriasiform lesions (Blaschko hyperkeratotic scaling), nail defects, cicatricial alopecia, follicular pitted scars, skeletal anomalies JAAD 33:356–360, 1995; Hum Genet 53:65–73, 1979; neonatal transient scaly plaques of the limbs, trunk, and scalp; scaly rash disappears in months leaving hypo- or hyperpigmented streaks with follicular atrophoderma and patchy scarring alopecia; CDPX2 – X-linked lethal in males; X-linked dominant (mosaic for emopamil-binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309– 1313, 2012 CHILD syndrome – congenital hemidysplasia, ichthyosis, limb defects, unilateral ichthyosiform erythroderma; ipsilateral hypoplasia of brain and bones Curr Prob Derm 14:71–116, 2002; Ped Derm 15:360–366, 1998; Dermatology 191:210–216, 1995 CHIME syndrome – colobomata, heart defects, ichthyosiform dermatosis of the flexures, mental retardation, and ear defects – autosomal recessive mutation in PIGL; Am J Med Genetics A173:1378–1382, 2017; congenital ichthyosis with islands of sparing; migratory plaques Am J Human Genetics 90:685–688, 2012; Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002 Ped Derm 18:252–254, 2001; J Med Genet 32:465–469, 1995 Chondrodysplasia punctata, rhizomelic type, ichthyosis Congenital ichthyosis-follicular atrophoderma-hypotrichosis-­ hypohidrosis syndrome JAAD 63:607–641, 2010; JID 129:862–869, 2009; Am J Med Genet 75:186–189, 1998 Congenital ichthyosis, hypogonadism, small stature, facial dysmorphism, scoliosis, and myogenic dystrophy Ann Genet 42:45–50, 1999 Congenital ichthyosis, retinitis pigmentosa, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, abnormal electroencephalogram Ophthalmic Genet 19:69–79, 1998 Congenital ichthyosis and keratoderma (Vohwinkel’s syndrome) Conradi-Hunermann syndrome (Happle’s syndrome) ( X-linked dominant chondrodysplasia punctata) (chondrodysplasia punctata, ichthyosis, cataract syndrome); mutation in EBP (emopamil-binding protein); autosomal recessive, collodion baby, or ichthyosiform erythroderma at birth; or onset in infancy, Blaschko pattern of erythroderma, and scaling; whorled ichthyosis of neonate Ped Derm

30:621–622, 2013; plantar hyperkeratosis; resolves in time to reveal whorl-like ichthyosiform hyperkeratosis heals with atrophy, swirls of fine scale, linear hyperpigmentation, follicular atrophoderma of arms and legs, cicatricial alopecia; skeletal defects with short stature severe autosomal rhizomelic type; X-linked recessive variant; bilateral sectoral cataracts, high-arched palate, shortening of humerus and femur (rhizomelic limb shortening); vertebral anomalies and facial defects; chondrodysplasia punctata; peroxisomal enzyme deficiency; AD 147:1073–1076, 2011; JAAD 63:607–641, 2010; BJD 157:1225–1229, 2007; JAAD 21:248–256, 1989; whorled thick or spiky hyperkeratosis in X-linked dominant Conradi-­ Hunermann syndrome JAAD 21:248–256, 1989; linear hyperkeratotic bands with diffuse erythema and scale, follicular atrophoderma, hypochromic areas, scalp alopecia, Curr Prob Derm 14:71–116, 2002; AD 127:539–542, 1991, Ped Derm 15:299–303, 1998; mutation in gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase Nat Genet 22:291–294, 1999; asymmetric shortening of legs Ped Derm 18:442–444, 2001; neonatal transient scaly plaques of the limbs, trunk, and scalp; CDPX2 – X-linked lethal in males; X-linked dominant (mosaic for emopamil-binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309–1313, 2012 Dermotrichic syndrome – X-linked recessive, congenital atrichia, ichthyosis, hypohidrosis Am J Med Genet 44:233–236, 1992 Down’s syndrome Dubowitz syndrome – autosomal recessive, microcephaly, sloping forehead, telecanthus, erythema and scaling of the face and extremities in infancy, ichthyosiform eruption, sparse blond scalp and arched eyebrow hair, dysplastic low-set ear pinnae, highpitched hoarse voice, delayed eruption of the teeth, growth retardation, craniofacial abnormalities; syndactyly, cryptorchidism, hypospadias, developmental delay, transitory short stature, hyperactive behavior, blepharophimosis, ptosis of the eyelids, epicanthal folds, broad nose, palate anomalies, micrognathia, and severe atopic dermatitis Ped Derm 22:480–481, 2005; Am J Med Genet 63:277–289, 1996; Ped Derm 12:130–133, 1995; Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959–964, 1993; Eur J Pediatr 144:574–578, 1986; Am J Med Genet 4:345–347, 1979; J Med Genet 2:12–17, 1965 Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema, and peeling at birth; very short stature, superficial skin fragility with crusts of the face and knees, alopecia of the scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene (encoding plakophilin (1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999 Ellis-van Creveld syndrome (chondroplastic dwarf with defective teeth and nails, and polydactyly) – autosomal recessive; chondrodysplasia, polydactyly, peg-shaped teeth or hypodontia, short upper lip bound down by multiple frenula; nail dystrophy, hair may be normal or sparse and brittle; cardiac defects; ichthyosis, palmoplantar keratoderma Ped Derm 18:485–489, 2001; J Med Genet 17:349–356, 1980; Arch Dis Child 15:65–84, 1940 Familial hemophagocytic lymphohistiocytosis – seborrheic dermatitis with purpura; ichthyosis-like Ped Derm 28:494–501, 2011

Ichthyosiform Eruptions 553 Familial peeling skin syndrome – autosomal recessive; superficial peeling Curr Prob Derm 14:71–116, 2002 Familial pityriasis rubra pilaris – ichthyosiform scaling; psoriasiform dermatitis; gain-of-function mutation of CARD14 BJD 171:420–422, 2014; Am J Hum Genet 91:163–170, 2012 Fanconi syndrome, ichthyosis, dysmorphism, jaundice, and diarrhea Pediatr Nephrol 4:308–313, 1990 Giroux-Barbeau type (spinocerebellar ataxia with erythrokeratodermia) – autosomal dominant; scaling plaques with progressive neurologic symptoms; EVOVL mutation JAMA Neurol 72:942–943, 2015 sss H syndrome (low height, heart, hallux valgus, hormonal, hypogonadism, hematologic) – autosomal recessive; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; starts on the feet and legs and progresses upward; hypertrichosis, short stature, facial telangiectasia, ichthyosiform changes, gynecomastia, varicose veins, skeletal deformities (camptodactyly of fifth fingers), scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, micropenis, azoospermia, sensorineural hearing loss, dilated scleral vessels, exophthalmos, cardiac anomalies, hepatosplenomegaly, mental retardation; mutation in nucleoside transporter Hent3 JAAD 70:80–88, 2014; BJD 162:1132–1134, 2010; Ped Derm 27:65–68, 2010; JAAD 59:79–85, 2008 Haber’s syndrome AD 117:321–324, 1981; JAAD 40:862–865, 1999 Hallermann-Streiff syndrome Clin Exp Dermatol 29:477–479, 2004; Am J Med Genet C Semin Med Genetic 178:398–406, 2018 Harlequin fetus – ABCA12 mutation; lipid transfer gene regulates transfer of lipids into lamellar granules; intercellular lipid lamellae are absent Cell Tissue Res 351:281–288, 2013; AD 147:681–686, 2011 HID syndrome (hystrix-like ichthyosis with deafness) – autosomal dominant; shark-skin appearance, sensorineural deafness, generalized spiky and cobblestoned hyperkeratosis, neonatal erythroderma, scarring alopecia, occasional punctate keratitis; probably variant of KID syndrome with mutation of connexin 26 (gap junction protein) BJD 146:938–942, 2002 Ichthyosiform erythroderma and cardiomyopathy BJD 139:1055– 1059, 1998 Ichthyosiform erythroderma and defective chemotaxis J Pediatr 87:908–911, 1975; AD 106:755–756, 1972; elevated IgE J Pediatr 87:908–911, 1975; IgM and IgG deficiencies Dermatol Monatschr 157:525–531, 1971 Ichthyosis, abnormal platelet function, asplenism, migraine, dyslexia Clin Genet 28:367–374, 1985 Ichthyosis congenita BJD 136:377–379, 1997 Ichthyosis-cheek-eyebrow syndrome (ICE syndrome) – ichthyosis vulgaris, fullness of cheeks, thinning of eyebrows; dysmorphic features, skeletal anomalies Clin Genet 31:137–142, 1987 Ichthyosis, follicular atrophoderma, eyebrow hypotrichosis, woolly hair BJD 147:604–606, 2002; Am J Med Genet 75:186–189, 1998 Ichthyosis, gastric hyperplasia, subungual hyperkeratosis, immunologic dysfunction; TTC7A mutations BJD 175:1061, 2016 Ichthyosis hypotrichosis syndrome JAAD 63:607–641, 2010; Am J Hum Genet 80:467–477, 2007 Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis Clin in Dermatol 23:47–55, 2005 Ichthyosis, mental retardation, asymptomatic spasticity AD 126:1485–1490, 1990

Ichthyosis with neurologic and eye abnormalities AD 121:1149– 1156, 1985  Keratitis ichthyosis deafness (KID) syndrome – autosomal recessive; dotted waxy, fine granular, stippled, or reticulated surface pattern of severe diffuse hyperkeratosis of palms and soles (palmoplantar keratoderma), ichthyosis with well-marginated, serpiginous erythematous verrucous plaques, hyperkeratotic elbows and knees, ichthyosis with reddish hue, perioral furrows, leukoplakia, bilateral sensory deafness, photophobia with vascularizing keratitis, photophobia with vascularizing keratitis, blindness; hypotrichosis of the scalp, eyebrows, and eyelashes, dystrophic nails, chronic mucocutaneous candidiasis, otitis externa, abscesses, blepharitis; hyperkeratotic papules and plaques of the face, scalp, trunk, extremities; exaggerated diaper dermatitis; connexin 26 (GJB2) mutations AD 147:993–994, 2011; BJD 156:1015–1019, 2007; Ped Derm 23:81–83, 2006; JAAD 51:377–382, 2004; BJD 148:649–653, 2003; Cutis 72:229–230, 2003; ; Ped Derm 19:285–292, 2002; Ped Derm 15:219–221, 1998; Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990;JAAD 23:385–388, 1990; JAAD 19:1124–1126, 1988; AD 123:777–782, 1987; AD 117:285–289, 1981; J Cutaneous Dis 33:255–260, 1915; KID syndrome with secondary dermatophytosis – cobblestoned palmoplantar keratoderma with ichthyosiform changes of the face AD 148:1199–1204, 2012   Netherton’s syndrome  Refsum’s disease – autosomal recessive, childhood onset, deficiency of alpha phytanic acid hydroxylase, resembles ichthyosis vulgaris, cataracts, night blindness, polyneuritis, retinitis pigmentosa, ataxia AD 123:85–87, 1987  Sjogren-Larsson syndrome – autosomal recessive, lamellar ichthyosis, mental deficiency, macular degeneration of the retina, spastic paralysis, fatty alcohol oxidoreductase deficiency Curr Prob Derm 14:71–116, 2002  Trichothiodystrophy (Tay’s syndrome) – BIDS (brittle hair, intellectual impairment, decreased fertility, short stature) Immuno-osseous dysplasia – ichthyosis, metaphyseal dysplasia, short-limbed dwarfism, immunodeficiency with impaired cellular immunity, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation); Ped Derm 23:373–377, 2006; J Pediatr 119:64–72, 1991 IPEX syndrome – X-linked; immune dysregulation, polyendocrinopathy (diabetes mellitus, thyroiditis), autoimmune enteropathy; mutation of FOXP3 gene encodes DNA-binding protein that suppresses transcription of multiple genes involved in cytokine production and T-cell proliferation; atopic-like or nummular dermatitis, ichthyosiform dermatitis, urticaria, scaly psoriasiform plaques of the trunk and extremities, penile rash, alopecia universalis, trachyonychia, bullae; pemphigoid nodularis (bullae and prurigo nodularis), membranous glomerulonephritis, autoimmune thyroid disease, hepatitis, exocrine pancreatitis NEJM 378:1132–1141, 2018; JAAD 55:143–148, 2006; AD 140:466–472, 2004; J Pediatr 100:731–737, 1982 Kallmann’s syndrome – association of X-linked recessive ichthyosis with hypogonadotrophic hypogonadism, anosmia, nystagmus, synkinesis (mirror movements of hands and feet) Int J Impot Res 12:269–271, 2000; J Pediatr Endocrinol Metab 11:631–638, 1998; Am J Ment Def 48:203–236, 1944 MAUIE syndrome – micropinnae, alopecia universalis, congenital ichthyosis, ectropion JAAD 37:1000–1002, 1997; JAAD 33:884–886, 1995 Male emopamil-binding protein disorder (MEND) with neurologic defects – severe neurologic defects, mild ichthyosis BJD 166:1309– 1313, 2012

554 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 MEDNIK syndrome – autosomal recessive; disorder of copper metabolism; ichthyosis, hearing loss, peripheral neuropathy, keratoderma; intellectual disability; mutation in APIS1 Metab Brain Dis 33:2065–2068, 2018 MELAS syndrome (mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like episodes) – ichthyosiform diffuse erythema JAAD 41:469–473, 1999 MEND – X-linked recessive; hypomorphic mutation of emopamil-­ binding protein; diffuse mild ichthyosis; telecanthus, prominent nasal bridge, low-set ears, micrognathia, cleft palate large anterior fontanelle, polydactyly, 2/3 syndactyly, kyphosis, Dandy-Walker malformation, cerebellar hypoplasia, corpus callosal hypoplasia, hydrocephalus, hypotonia, developmental delay, seizures; bilateral cataracts, glaucoma, hypertelorism; cardiac valvular and septal defects, hypoplastic aortic arch; renal malformation, cryptorchidism, hypospadias BJD 166:1309–1313, 2012 Mental retardation-enteropathy-deafness-neuropathy-ichthyosis-­­ keratodermia syndrome JAAD 63:607–641, 2010; Proc Natl Acad Sci USA 4:1–9, 2009 Miller syndrome – defective neutrophil chemotaxis Naegeli-Franceschetti-Jadassohn syndrome JAAD 28:942–950, 1993 Neonatal ichthyosis-sclerosing cholangitis syndrome – autosomal recessive; lamellar ichthyosis, scalp hypotrichosis, scarring alopecia, sclerosing cholangitis; congenital paucity of bile ducts; oligodontia, hypodontia, dysplastic enamel; mutation in CLDN1 (claudin-1; a tight junction component) BJD 170:976–978, 2014; JAAD 63:607–641, 2010; BJD 163:205–207, 2010; Hum Mutat 27:408–410, 2006; Clin Dermatol 23:47–55, 2005; Gastroenterol 127:1386–1390, 2004; JID 119:70–76, 2002 Netherton’s syndrome – autosomal recessive; erythroderma in infancy; serpiginous papulosquamous ichthyosiform eruption, ichthyosis linearis circumflexa JAMADerm 156:350–351, 2020; trichorrhexis nodosa BJD 178:335–349, 2018; BJD 159:744–746, 2008; Curr Prob Derm 14:71–116, 2002; Ped Derm 13:183–199, 1996 Neu-Laxova syndrome – variable presentation; tight translucent skin, mild scaling to harlequin ichthyosis appearance; ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema and mildly edematous feet and hands, absent nails; microcephaly, abnormal facies with exophthalmos, intrauterine growth retardation, limb deformities and contractures, low-set ears, sloping forehead, short neck; small genitalia, eyelid and lip closures, syndactyly, cleft lip and palate, micrognathia; central nervous system abnormalities; autosomal recessive; uniformly fatal JAAD 63:607–641, 2010; Ped Derm 20:25–27,78–80, 2003; Curr Prob Derm 14:71–116, 2002; Am J Med Genet 35:55–59, 1990 Noonan’s syndrome Oral and digital anomalies with ichthyosis Peeling skin syndrome Phacomatosis pigmentokeratotica – generalized ichthyosiform hyperkeratosis; coexistence of an organoid nevus and a checkerboard papular speckled lentiginous nevus; organoid nevus associated with hypophosphatemic vitamin D-resistant rickets JAAD 55:S16–20, 2006 POEMS syndrome – polyneuropathy, organomegaly (heart, kidneys, spleen), endocrinopathy, M protein, skin changes (angiomas, clubbed nails, hyperpigmentation, hypertrichosis, leukonychia, hyperhidrosis Cutis 61:329–334, 1998; JAAD 19:979–982, 1988 Refsum’s syndrome (phytanic acid oxidase deficiency) – autosomal recessive; late onset (teens to 30s), mild ichthyosis vulgaris-like, some with lamellar type scale; retinitis pigmentosa, cataracts; deafness, anosmia, sensorimotor polyneuropathy, ataxia Neurobiol

Dis 18:110–118, 2005; Curr Prob Derm 14:71–116, 2002; J R Soc Med 84:559–560, 1991 Restrictive dermopathy – autosomal recessive; collodion baby-like appearance; tightly adherent, shiny, translucent skin, prominent superficial vessels, generalized joint contractures, retromicrognathia, enlarged anterior fontanelle, dysplasia of clavicles, enlarged placenta with short umbilical cord; mutation of ZMPSTE24; loss of function of zinc metalloproteinase STE24 which is necessary for processing of nuclear intermediate filament protein prelamin A JAAD 63:607–641, 2010; BJD 159:961–967, 2008; AD 134:577– 579, 1998 Reticular ichthyosiform erythroderma with evolving patches of normal skin, hypertrichosis, no collodion membrane Dermatology 188:40–45, 1994 Rud’s syndrome – ichthyosis with hypogonadism; congenital ichthyosis, hypogonadism, mental retardation, retinitis pigmentosa, hypertrophic polyneuropathy Neuropediatrics 13:95–98, 1982 Rhizomelic dwarfism – autosomal recessive; chondrodysplasia punctata with mild ichthyosis Ped Derm 18:442–444, 2001 Shwachman’s syndrome (ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis, growth retardation, metaphyseal dysplasia) Ped Derm 9:57–61, 1992; AD 127:225–230, 1991; Arch Dis Child 55:331–347, 1980 Shokeir syndrome – proportionate short stature, absent thumbs, anosmia, ichthyosiform dermatosis, congenital heart defect Am J Med Genet 66:378–398, 1996 Sjogren-Larsson syndrome – autosomal recessive; non-bullous congenital ichthyosiform erythroderma, ichthyosis with light peeling of the trunk and lamellar-like ichthyosis of lower legs, yellow-brown hyperkeratosis around umbilicus, accentuated skin markings; mild to moderate mental retardation, spastic diplegia, short stature, kyphoscoliosis, retinal changes, yellow pigmentation, intertrigo (deficiency of fatty aldehyde dehydrogenase) Cutis 100:452–455, 2017; Cutis 78:61–65, 2006; Ped Derm 22:569–571, 2005; Curr Prob Derm 14:71–116, 2002; Chem Biol Interact 130–132:297–307, 2001; Am J Hum Genet 65:1547–1560, 1999; JAAD 35:678–684, 1996; Acta Psychiatr Scand 32:1–112, 1957 Tay’s syndrome (trichothiodystrophy) – collodion baby Pediatrics 87:571–574, 1991; ichthyosiform erythroderma Pediatrics 87:571– 574, 1991; Ped Derm 6:202–205, 1989 Trichothiodystrophy syndromes (BIDS, IBIDS, PIBIDS) – autosomal recessive; collodion baby, congenital erythroderma, sparse or absent eyelashes and eyebrows, sulfur-deficient short brittle hair with tiger tail banding on polarized microscopy, trichomegaly, brittle soft nails with koilonychia, premature aging, very short stature, microcephaly, sexual immaturity, ichthyosis, photosensitivity, hypohidrosis, high-arched palate, dysmyelination of white matter, bird-like facies, abnormal teeth with dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation; recurrent infections with neutropenia; ocular abnormalities, osteopenia; socially engaging personality; mutation in one of the three DNA repair genes (XPB, XPA, TTDA, or TTDN1) Ped Derm 36:668–671, 2019; Ped Derm 32:865–866, 2015; JAAD 63:323–328, 2010; Curr Prob Derm 14:71–116, 2002; JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997; Am J Med Genet 35:566–573, 1990; JAAD 16:940–947, 1987; Eur J Pediatr 141:147–152, 1984 Unusual facies, digital abnormalities, ichthyosis J Med Genet 26:339–342, 1989 Vohwinkel’s syndrome – knuckle papules, starfish keratoses in honeycomb pattern; palmoplantar keratoderma, ichthyosis, pseudoainhum ; hearing impairment, mutilating digital constriction bands JAAD 44:376–378, 2001

Immune Deficiency Syndromes with Bacterial Infections 555 XLRI with mild mental retardation, chondrodysplasia punctata and short stature Clin Genet 34:31–37, 1988 Zunich neuroectodermal syndrome – migratory ichthyosiform dermatosis Ped Derm 13:363–371, 1996

TOXINS Eosinophilia myalgia syndrome JAAD 25:512–517, 1991 Mothball intoxication (paradichlorobenzene) – refractory pruritus of arms and hands; ichthyosis AD 148:404–405, 2012; NEJM 355:423–424, 2006

TRAUMA Radiotherapy JAAD 40:862–865, 1999; ichthyosiform erythroderma due to megavoltage radiotherapy Cutis 48:59–60, 1991

 STK4 or macrophage-stimulating 1 (MST1) deficiency – cutaneous viral, bacterial, fungal infections; respiratory infections, cardiac anomalies   Tyk2 deficiency – complete tyrosine kinase 2 deficiency  Wiskott-Aldrich syndrome – X-linked recessive; T-cell lymphopenia, autoimmunity, malignancy recurrent bacterial and viral infections, vascular abnormalities, microthrombocytopenia; defect in X chromosome; WASP protein Biotin-responsive multiple carboxylase deficiency – alopecia, developmental delay, hypotonia, seizures, biotinidase deficiency Am J Med Genet 66:378–398, 1996 Bloom’s syndrome – autosomal recessive; short stature, telangiectatic erythema of face, photosensitivity; café au lait macules, eyebrow/eyelash hair loss, alopecia areata, cheilitis JAAD 75:855– 870, 2016; Am J Med Genet 66:378–398, 1996; low serum immunoglobulins (IgM and IgA commonly) J Clin Immunol 38:35– 44, 2018

Sympathectomy-induced ichthyosis-like eruption Int J Dermatol 39:146–151, 2000

Braegger syndrome – proportionate short stature, IUGR, ischiadic hypoplasia, renal dysfunction, craniofacial anomalies, postaxial polydactyly, hypospadias, microcephaly, mental retardation Am J Med Genet 66:378–398, 1996

VASCULAR DISORDERS

Bruton’s hypogammaglobulinemia – X-linked (90%) or autosomal recessive (10%) Ann DV 143:453–456, 2016; chronic leg ulcer due Helicobacter J Clin Microbiol 49:483–770, 2011

Lymphostasis

IMMUNE DEFICIENCY SYNDROMES WITH BACTERIAL INFECTIONS Acrodermatitis enteropathica Am J Med Genet 66:378–398, 1996 Adenine deaminase deficiency – autosomal recessive; disproportionate short stature; short limb skeletal dysplasia type 1 (bowed femurs); severe immunodeficiency Am J Med Genet 66:378–398, 1996; adenosine deaminase 2 (ADA2) mutation (mutation in CECR1); intermittent fevers, early-onset lacunar strokes, livedoid eruption, hepatosplenomegaly, systemic vasculopathy; hypogammaglobulinemia Ped Derm 33:602–614, 2016; NEJM 370:911–920, 2014 Alpha-mannosidosis – autosomal recessive; hepatosplenomegaly, psychomotor retardation, dysostosis multiplex Am J Med Genet 66:378–398, 1996 Anhidrotic ectodermal dysplasia with immunodeficiency – mutation in NEMO JAAD 47:169–187, 2002 Ataxia-telangiectasia – autosomal recessive; cutaneous granulomas; immunodeficiency, cancer susceptibility, and radiation sensitivity; low levels of one or more immunoglobulins (IgG, IgM, IgA, or IgG subclasses); lymphopenia especially T lymphocytes and failure to make antibodies to vaccines or infections; premature graying of hair, vitiligo, warts, sinopulmonary infections Orphanet J Rare Dis 11:159 Nov 25, 2016; Pediatric Critical Care Med 13:e84–90, 2012; Clin in Dermatol 23:68–77, 2005; Am J Med Genet 66:378–398, 1996 Severe atopic dermatitis, elevated IgE levels, and recurrent infections Dermatol Clin 35:11–19, 2017  DOCK8 syndrome – autosomal recessive form of hyper IgE syndrome   Hyper IgE syndrome (Job’s syndrome) – STAT3 mutation  Omenn syndrome – severe combined immunodeficiency; severe erythroderma, infections, lymphadenopathy, hepatosplenomegaly  Phosphoglucomutase 3 (PGM3) deficiency – atopy and hypergammaglobulinemia, developmental delay

C3 deficiency – dermatitis; recurrent infections, vasculitis, LE; C3 inactivator deficiency (dermatitis early in infancy) CARD9 (caspase recruitment, domain-containing protein 9) deficiency – mucocutaneous and central nervous system candidiasis of brain parenchyma or meninges Clin Inf Dis 59:81–84, 2014; dermatophytes Cartilage-hair hypoplasia (metaphyseal chondrodysplasia of McKusick) (disproportionate short stature; short limb skeletal dysplasia) – autosomal recessive; dwarfism, mild leg bowing with short limbs, short sparse, lightly colored hair; some with total baldness, immune defects; mutation in mitochondrial RNA processing; endoribonuclease; 9p13 JAAD 54:S8–10, 2006; Clin in Dermatol 23:68–77, 2005; Am J Med Genet 66:378–398, 1996; Eur J Pediatr 155:286–290, 1996; Eur J Pediatr 142:211–217, 1993; Am J Med Genet 41:371–380, 1991; Bull Johns Hopkins Hosp 116:285–326, 1965 Chediak-Higashi syndrome – abnormal giant lysosomes and granules; metallic silver hair; platelet dysfunction; poor vision; defective killing intracellular and extracellular pathogens Clin in Dermatol 23:68–77, 2005; Am J Med Genet 66:378–398, 1996 Chronic blepharitis and pyoderma of the scalp – with hypercupremia and decreased intracellular killing Ped Derm 1:134–142, 1983 Chronic granulomatous disease – X-linked or autosomal recessive, seborrheic dermatitis-like changes, Xp21 (distal end of Xp), localized pyodermas, abscesses, granulomas, perioral and intraoral ulcers, lungs/liver/spleen, defect in NADPH oxidase system; including NADPH, phagocyte cytochrome b, and cytosolic proteins; membrane-associate NADPH oxidase system fails to produce superoxide and other toxic oxygen metabolites; Staphylococcus aureus, Klebsiella, Pseudomonas, Escherichia coli, Serratia, Aspergillus, Candida, Cryptococcus, Nocardia Int Arch Allergy Immunol 170:62–73, 2019; NEJM 352:64–69, 2005 Chronic mucocutaneous candidiasis (APECED) – cutaneous granulomas Advances Dermatol 23:197–229, 2007 Combined bacterial, viral, and mycotic infections BJD 178:335–349, 2018   Adenosine deaminase deficiency   Artemis deficiency

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

IL7Ra deficiency JAK3 deficiency RAG1/RAG2 deficiency Schimke syndrome Severe combined immunodeficiency X-chromosomal – IL2RG

Common variable immunodeficiency – granulomatous dermatitis with annular atrophic scarred and scaly plaques J Clin Immunol 33:84–95, 2013; Dermatovenereol 18:107–113, 2010; J Clin Immunol 117:878–882, 2006; BJD 147:364–367, 2002; Mt Sinai Med J 68:326–330, 2001; epidermodysplasia verruciformis–like lesions in common variable immunodeficiency Clin Inf Dis 51:195– 196,248–249, 2010 Complement deficiencies, inherited, classical, and alternate pathway (defects in activating C3) – pyogenic bacteria including S. pneumonia; defects C5–C9, Neisseria species Iran J Immunol 15:309–320, 2018 Defective intracellular killing, pyoderma, blepharitis, scarring alopecia Deletion of short arm of chromosome 18 – mental and growth deficiency, microcephaly, ptosis Am J Med Genet 66:378–398, 1996 Deletion of long arm of chromosome 18 – midface hypoplasia, microcephaly, mental retardation, nystagmus Am J Med Genet 66:378–398, 1996 Deletion of chromosome 22:q11 (DiGeorge/velo-cardio-facial syndrome) – aortic arch anomalies, hypocalcemia, facial defects, thymic hypoplasia Am J Med Genet 66:378–398, 1996 DiGeorge’s syndrome – “Catch-22” pneumonia; conotruncal cardiac anomalies, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia; 22q11.2 microdeletion Stat Pearls Feb 17, 2020 DNA ligase I deficiency – short stature, photosensitivity JCI 128:5489–5504, 2018; Am J Med Genet 66:378–398, 1996 DOCK8 deficiency syndrome (dedicator of cytokinesis 8 gene) – immunodeficiency; resembles Job’s syndrome; decreases T and B cells; increased IgE, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; warts, dermatitis, asthma, cutaneous staphylococcal abscesses; malignancies: aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by the presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation Dermatol Clin 35:11–19, 2017; JAAD 73:355–364, 2015; AD 148:79–84, 2012 Dubowitz syndrome – occasional immunodeficiency; dermatitis, IgA deficiency, esophageal cancer Front Immunol 8:449, May 1, 2017; Tokai J Exp Clin Med 36:29030, 2011; Ped Allergy Immunol 22:313–319, 2011 Am J Med Genet 66:378–398, 1996 Dyskeratosis congenita JAAD 77:1194–1196, 2017; Am J Med Genet 66:378–398, 1996 Fanconi pancytopenia – autosomal recessive; radial hypoplasia, hyperpigmentation, pancytopenia Am J Med Genet 66:378–398, 1996 5’Nucleotidase elevation – increased nucleotide catabolism, developmental delay, seizures, megaloblastic anemia, aggressive behavior Am J Med Genet 66:378–398, 1996 Fleischer syndrome – proportionate short stature, displacement of nipples, occasional polymastia, hypoplasia of kidneys; hypogammaglobulinemia, isolated growth hormone deficiency Am J Med Genet 66:378–398, 1996

Folic acid malabsorption (transport defect) – megaloblastic anemia, convulsions, movement disorder Am J Med Genet 66:378–398, 1996 Frenkel-Russe syndrome – retinal telangiectasias, recurrent infections; hypogammaglobulinemia Am J Med Genet 66:378–398, 1996 Galactosemia – autosomal recessive; hepatomegaly, hypoglycemia, jaundice, feeding difficulties; bacterial infections, hepatosplenomegaly, cataracts, hypotonia, Medicina (Kaunas)55:91 April 14, 2019; Am J Med Genet 66:378–398, 1996 Glutathione synthetase deficiency – autosomal recessive; hemolytic anemia, acidosis with anion gap, neutropenia, decreased bactericidal activity, failure to assemble microtubules; recurrent bacterial infections Orphanet J Rare Dis 2:16 March 30, 2007; J Ped 139:79–84, 2001; Am J Med Genet 66:378–398, 1996 Glycogen storage disease Ib – autosomal recessive; recurrent infection, neutropenia, glucose-6-phosphate transport defect Am J Med Genet 66:378–398, 1996 Good syndrome – adult-acquired primary immunodeficiency in context of past or current thymoma; sinopulmonary infections; lichen planus, oral lichen planus of the tongue, gingivitis, oral erosions Curr Opin Infect Dis 31:267–277, 2018; BJD 172:774–777, 2015; Am J Med Genet 66:378–398, 1996 Griscelli syndrome type 2 – autosomal recessive; silver gray hair, light skin color, recurrent pyogenic infections; episodic fever, hepatosplenomegaly, lymphadenopathy; RAB27A mutation; immunodeficiency and pigmentary abnormalities Clin in Dermatol 23:68–77, 2005; Am J Med Genet 66:378–398, 1996 Hallermann-Streiff syndrome (autosomal dominant; occasional immunodeficiency) – thin pinched nose, congenital cataracts, hypotrichosis, microphthalmia Am J Med Genet 66:378–398, 1996 Hermansky-Pudlak syndrome type 2 – recurrent bacterial infections; upper respiratory infections, otitis media, pneumonia; mutation in AP3B1 gene Orphanet J Rare Dis 8:168, Oct 17, 2013 Hutchinson-Gilford syndrome – autosomal dominant; occasional immunodeficiency Am J Med Genet 66:378–398, 1996 Hyper IgE syndrome (Job’s syndrome) (Buckley’s syndrome) – dermatitis of the face, scalp, axillae, and groin; recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract; papular, pustular, excoriated dermatitis of the scalp, buttocks, neck, axillae, groin; furunculosis; growth failure; dermatitis of the face, behind the ears, scalp, axillae, and groin; recurrent bacterial infections of the skin with cold abscesses, contact urticaria, infections of nasal sinuses, and respiratory tract; STAT3 mutations JAAD 73:355–364, 2015; Clin in Dermatol 23:68–77, 2005; J Pediatr 141:572–575, 2002; NEJM 340:692–702, 1999; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983; Lancet 1:1013–1015, 1966 Ped Derm 30:621–622, 2013; NEJM 357:1608– 1619; JAAD 54:855–865, 2006; AD 140:1119–1125, 2004; J Pediatr 141:572–575, 2002; Curr Prob in Derm 10:41–92, 1998; Medicine 62:195–208, 1983; Pediatrics 49:59–70, 1972; Lancet 1:1013–1015, 1966 Hyper IgM syndrome (hypogammaglobulinemia with hyper IgM) – X-linked with mutation in CD40 ligand gene with CD40 deficiency, NEMO deficiency; low IgA and IgG; sarcoid-like granulomas; multiple papulonodules of the face, buttocks, arms Ped Derm 21:39–43, 2004 extracellular bacteria, Pneumocystis jirovecii, Cryptosporidium parvum ICF syndrome (immunodeficiency, centromeric instability-facial anomalies) – autosomal recessive; variable immune deficiency, mental retardation, chromosomal instability, facial dysmorphism Am

Immune Deficiency Syndromes with Bacterial Infections 557 J Med Genet 66:378–398, 1996; Job’s syndrome (hyper IgE syndrome) (Buckley’s syndrome): chronic recurrent Staphylococcus (cold) abscesses, hyperextensible joints, red hair, female, hyper IgE syndrome J Pediatr 141:572–575, 2002; NEJM 340:692–702, 1999; Lancet 1:1013–1015, 1966 Hyper IgM syndrome, B-cell intrinsic – AID and UNG deficiency; extracellular bacteria Interferon regulatory factor 8 (IRF*) – autosomal recessive; susceptible to intracellular bacteria IRAK-4 deficiency (homozygous mutations of IL-receptorassociated kinase 4 gene) – cutaneous infections with Staphylococcus aureus; abscesses, cellulitis, impetigo JAAD 54:951–983, 2006; chilblains Clin Exp Dermatol 43:596–597, 2018; Staphylococcus aureus, Streptococcus pneumonia Ped Int 57:1166–1169, 2015 Jacobsen syndrome – 11q terminal deletion and combined immunodeficiency; recurrent bacterial and prolonged viral infections Am J Med Genet 170:3237–3240, 2016 Jung syndrome – pyoderma, folliculitis, atopic dermatitis, response to histamine-1 antagonist Am J Med Genet 66:378–398, 1996 Kotzot syndrome – autosomal recessive; tyrosinase-positive oculocutaneous albinism, granulocytopenia, thrombocytopenia, recurrent bacterial infections, microcephaly, mental retardation Am J Med Genet 66:378–398, 1996 Krawinkel syndrome – lissencephaly, abnormal lymph nodes, spastic tetraplegia, transient arthritis, mental; immunodeficiency associate with recurrent infections Am J Med Genet 66:378–398, 1996; Am J Med Genet 33:436–443, 1989 Leukocyte adhesion deficiency (LAD) syndrome types 1, 2, and 3 – autosomal recessive; impaired wound healing, pyogenic bacterial infections with the absence of pus; pyoderma gangrenosum-like ulcers in LAD 1; periodontitis, delayed separation of the umbilical cord, neutrophilia Stat Pearls Nov 15, 2019; Ped Der 28:156–161; Clin in Dermatol 23:68–77, 2005 Methylmalonic aciduria – autosomal recessive; acidosis, recurrent severe infection Am J Med Genet 66:378–398, 1996; fulminant ecthyma gangrenosum Dermatoendocrinol 2:60–61, 2010; AD 133:1563–1566, 1997

Orotic aciduria type I (autosomal recessive) – megaloblastic anemia, severe infection Am J Med Genet 66:378–398, 1996 Osteopetrosis-lymphedema-ectodermal dysplasia (OL-HED-ID) syndrome Eur J Ped 169:1403–1407, 2010; Ped Derm 31:716–721, 2014; AD 144:342–346, 2008; Curr Opin Immunol 16:34–41, 2004; Hum Mol Genet 11:2371–2375, 2002 Papillon-Lefevre syndrome – autosomal recessive; diffuse palmoplantar keratoderma; rapidly progressive periodontitis; decreased peripheral CD3, CD4 J Dermatol 29:329–335, 2002; Am J Med Genet 66:378–398, 1996 Periodic fever, immunodeficiency, and thrombocytopenia – severe oral ulcers leading to scarring and microstomy; fever, poor growth, infections, thrombocytopenia Ped Derm 33:602–614, 2016 Phagocyte deficiencies – chronic granulomatous disease, leukocyte adhesion deficiency syndrome Stat Pearls Nov 22, 2019; J Allergy Clin Immunol Pract 6:1418–1420, 2018 PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – autosomal dominant; evaporative cold urticaria; neonatal ulcers in cold-sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of the nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of the cheeks, forehead, ears, chin; crusted, ulcerated eroded plaque of the nasal tip, ears, tips of fingers and toes (acral necrosis); atopy; recurrent sinopulmonary infections; autoimmune diseases Ped Derm 37:147–149, 2020; JAMADerm 151:627–634, 2015 Powell syndrome – X-linked, intractable diarrhea, autoimmune polyendocrinopathy, dermatitis, hemolytic anemia Am J Med Genet 66:378–398, 1996 Primary intestinal lymphangiectasia (Waldmann’s disease) – autosomal dominant, lower limb edema, loss of immunoglobulin and lymphocytes into gastrointestinal tract; protein losing enteropathy; lymphopenia, hypoalbuminemia, and hypogammaglobulinemia; risk of pyogenic infection not significantly elevated Orphanet J Rare Dis 3:5 Feb22, 2008; Am J Med Genet 66:378–398, 1996 Primary sclerosing cholangitis with immunodeficiency – autosomal recessive Am J Med Genet 66:378–398, 1996

Mulibrey nanism – autosomal recessive, proportionate short stature, prenatal growth deficiency, muscle weakness, abnormal sella turcica, hepatomegaly, ocular fundi lesions; pericardial constriction; TRIM37 mutation J Med Genet 41:92–98, 2004; Am J Med Genet 66:378–398, 1996

Propionic acidemia – autosomal recessive; acidosis, vomiting, ketosis Am J Med Genet 66:378–398, 1996

Mulvihill-Smith syndrome – autosomal dominant; proportionate short stature, microcephaly, unusual facies (broad forehead, small face, micrognathia), multiple pigmented nevi, hypodontia, immunodeficiency with chronic infections, high-pitched voice, progeroid, conjunctivitis, delayed puberty BMC Neurol 14:4, Jan 7, 2014; Am J Med Genet 66:378–398, 1996; J Med Genet 31:707–711, 1994

Ritscher-Schinzel syndrome – autosomal recessive; craniofacial features, cerebellar defects (Dandy Walker-like malformation), wavy pattern on skull X-rays; atrioventricular canal defect, short stature; recurrent infection Gene Reviews Jan 23, 2020; Am J Med Genet 66:378–398, 1996

Netherton syndrome – severe atopic diathesis; APINK5 mutation JID 128:1148–1159, 2008; Am J Med Genet 66:378–398, 1996 Nijmegen breakage syndrome – autosomal recessive; microcephaly, mental retardation, prenatal-onset short stature, bird-like facies, café au lait macules; recurrent sinopulmonary infections; predisposition to malignancy; radiosensitivity Orphanet J Rare Dis Feb 28, 2012; Am J Med Genet 66:378–398, 1996 Omenn syndrome – disproportionate short stature, short limb skeletal dysplasia type 1; alopecia, eosinophilia, ichthyosiform skin lesions, reticuloendotheliosis, erythroderma; diarrhea, lymphadenopathy, hypogammaglobulinemia with elevated IgE level Am J Med Genet 66:378–398, 1996

Purine nucleoside phosphorylase (PNP) deficiency – severe immunodeficiency, neurologic findings, hemolytic anemia Am J Med Genet 66:378–398, 1996

Rubinstein-Taybi syndrome – occasional humoral immunodeficiency Clin Genet 89:355–358, 2016; Am J Med Genet 66:378–398, 1996 Schimke immuno-osseous T-cell dysplasia – ichthyosis, metaphyseal dysplasia, short-limbed dwarfism, immunodeficiency with impaired cellular immunity, hypotonia, sparse scalp hair, bullae, facial dyschromatosis (mottled hyper- and hypopigmentation); steroid-resistant nephrotic syndrome; pigmentary skin changes; defective cutaneous elastic fibers Ped Derm 23:373–377, 2006; Am J Med Genet 66:378–398, 1996; J Pediatr 119:64–72, 1991 Shwachman’s syndrome – disproportionate short stature, metaphyseal dysplasia, exocrine pancreatic insufficiency, cyclic neutropenia; recurrent bacterial infections Stat Pearls May 29, 2020; Am J Med Genet 66:378–398, 1996

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Schwartz-Jampel syndrome – autosomal recessive; occasional immunodeficiency; epiphyseal dysplasia, short stature, myotonic myopathy, myopia, joint contractures Am J Med Genet 66:378–398, 1996 Seckel syndrome – occasional immunodeficiency; bird-like facies, microcephaly, mental retardation Am J Med Genet 66:378–398, 1996 Severe congenital neutropenia (SCN) (Kostmann’s syndrome) – cyclic neutropenia;

X-linked severe combined immunodeficiency (SCID-X1) – most frequent form of SCID; mutation in IL2RG on X chromosome NEJM 380:1525–1534, 2019 ZAP-70 deficiency – exfoliative erythroderma; primary immune deficiency syndrome Ped Derm 37:561–562, 2020

mutation in ELA2

INGUINAL LYMPHADENITIS AND RASH

Shokeir syndrome – proportionate short stature, absent thumbs, anosmia, ichthyosiform dermatosis, congenital heart defect Am J Med Genet 66:378–398, 1996

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION

Short limb skeletal dysplasia type 3 – metaphyseal dysplasia, exocrine pancreatic insufficiency, cyclic neutropenia Am J Med Genet 66:378–398, 1996

Chronic granulomatous disease J Clin Immunol 3:287–291, 1983 Lupus erythematosus Semin Arthritis Rheum 26:477–482, 1996

Smith-Lemli-Opitz syndrome – autosomal recessive; occasional immunodeficiency; cryptorchidism, partial syndactyly of the second and third toes, anteverted nostrils, defect in cholesterol metabolism; reduced cholesterol biosynthesis due to mutation in DHCR7 J Ped End Met 31:451–459, 2018; Am J Med Genet 66:378–398, 1996; microcephaly, photosensitivity to UVA, hypospadias, bilateral cryptorchidism Gene Reviews Jan 30, 2020

Linear scleroderma, polymyositis J Dermatol 43:1224–1227, 2016

STAT1 gain-of-function mutation – chronic demodicidosis; recurrent staphylococcal infections of the lungs and skin, mycobacterial infections, cutaneous viral infections, invasive fungal infections; also cerebral aneurysms and cancers J Clin Immunol 36:73–84, 2016; Ped Derm 37:153–155, 2020

DRUGS

Toriello syndrome – autosomal recessive; proportionate short stature, prenatal growth deficiency, delayed skeletal maturation, cataracts, enamel hypoplasia, neutropenia, microcephaly, mental retardation Am J Med Genet 66:378–398, 1996 Transcobalamin II deficiency – autosomal recessive; transport protein for B12, severe megaloblastic anemia, leukopenia, thrombocytopenia Am J Med Genet 66:378–398, 1996 Trichothiodystrophy (with ERCC2 mutation (excision repair)) – matted twisted hair with ichthyosis; collodion baby, neutropenia and hypogammaglobulinemia, poor growth Ped Derm 36:668–671, 2019

DEGENERATIVE DISORDERS Incarcerated inguinal hernia; inguinal hernia mimicking lymphadenopathy Clin Nucl Med 8:183, 1983

BCG vaccination Duodecim 120:2247–2250, 2004 Dilantin Drug Intell Clin Pharm 17:460–462, 1983 DRESS – with reactivation of EBV and/or CMV Ann Dermatol 30:71–74, 2018 Drug eruptions – multiple types; “sulfasalazine syndrome” Forensic Sci Int 122:79–84, 2001 Stevens-Johnson syndrome Allergy Ashtma Proc 17:75–78, 1996

EXOGENOUS AGENTS Metal release from a prosthesis J Bone Joint Surg Br 75:266–269, 1993; joint silicone arthroplasty Foot Ankle 6:216–218, 1986 Petroleum jelly penile paraffinoma Can Urol Assoc 56:E137–139, 2012

Turner syndrome – missing or abnormal X chromosome (XO, isoX, ring X) Am J Med Genet 66:378–398, 1996

Silicone migration after buttock augmentation Plast Reconstr Surg Glob Open 65:e1583, 2017

Vici syndrome – agenesis of corpus callosum, cleft lip, oculocutaneous hypopigmentation, cataracts; cardiomyopathy, combined immunodeficiency, skeletal myopathy, recurrent infections Orphanet J Rare Dis 11:21, Feb 29, 2016; Am J Med Genet 66:378–398, 1996

Tattoo pigment lymphadenopathy OB Gyn 120:442–444, 2012

WHIM syndrome – warts, hypoglobulinemia, recurrent bacterial infections, myelokathexis; mutation in chemokine receptor CXCR4 Blood 130:2491–2498, 2017; Curr Mol Med 11:317–325, 2011; Ped Derm 26:155–158, 2009; Nat Genet 34:70–74, 2003; J Biol Chem 276:42826–42833, 2001 Wiskott-Aldrich syndrome – chronic eczematous dermatitis resembling atopic dermatitis, recurrent infections in male infants (pyodermas, otitis media), thrombocytopenic purpura with enlarged platelets; elevated IgE, IgA J Clin Immunol 38:13–27, 2018; Dermatol Clin 35:11–19, 2017; Clin in Dermatol 23:68–77, 2005; Am J Med Genet 66:378–398, 1996 Xeroderma pigmentosum – autosomal recessive Am J Med Genet 66:378–398, 1996 X-linked agammaglobulinemia – loss of BTK tyrosine kinase, no B cells; infection by extracellular bacteria and enteroviruses

INFECTIONS AND INFESTATIONS Bartonella henselae Infez Med 16:91–93, 2008 Basidiobolomycosis, subcutaneous Ghan Med J 51:43–46, 2017 Capnocytophaga J Clin Microbiol 29:832–833, 1991 Cat scratch disease (Bartonella henselae) Rev Med Interne 32:e34–36, 2011; Intez Med 16:91–93, 2008 J Clin Microbiol 38:2062–2064, 2000 Chancroid Sex Transm Infec 79:68–71, 2003; Br J Vener Dis 59:265–268, 1983 Ecthyma AD 132:823, 826, 1996 Entamoeba histolytica Mayo Clin Proc 75:513–516, 2000 Filariasis (Wuchereria bancrofti) Ann Trop Med Parasitol 99:759– 769, 2005; Am J Trop Med Hyg 45:325–331, 1991; Am J Trop Med Hyg 31:942–952, 1982 Gonococcal urethritis Mil Med 137:107–108, 1972

Inguinal Lymphadenitis and Rash 559 Herpes simplex, genital Case Rep Pathol 2015:573230; Histopathology 19:355–360, 1991; HSV lymphadenitis in chronic lymphocytic leukemia NEJM 380:859–868, 2019

Kikuchi’s disease BMJ Case Rep Sept 8, 2014; Schweiz Rundsch Med Prax 89:671–674, 2000; Clin Rheumatol 15:81–83, 1996 Sarcoidosis Proc(Baylor Univ Med(Rnt)26:161–162, 2013

Insect bite reaction Hautarzt 70:47–50, 2019 Leishmaniasis Int J Derm 28:248–254, 1989 Loa loa Am J Trop Med Hyg 33:395–402, 1984 Lymphogranuloma venereum – inguinal buboes JAAD 54:559–578, 2006;J Inf Dis 160:662–668, 1989

METABOLIC DISORDERS Uremic pruritus Clin Nephrol 66:472–475, 2006

Majocchi’s granuloma Exp Clin Transplant 4:518–520, 2006; invasive dermatophyte infection Clin Exp Dermatol 30:506–508, 2005

NEOPLASTIC DISORDERS

Melioidosis (Burkholderia pseudomallei) BMC Res Notes June 14, 2014

Cancer, including penile carcinoma Int J STD AIDS 27:323–325, 2016; Urol Int 47:108–109, 1991

Mycobacteria, non-tuberculous J Pediatr Surg 36:1337–1340, 2001; M. chelonae Dermatology 187:299–300, 1993; Dermatologica 160:376–379, 1980

Castleman’s disease BMJ Case Rep Auf 16, 2017

Mycobacterium haemophilum Ped Inf Dis J 26:84–86, 2007 Mycobacterium marinum Eur J Pediatr 177:1389–1393, 2018 Mycobacterium massiliense – after body piercing Eur J Dermatol 26:635–637, 2016 Mycobacterium tuberculosis Am J Trop Med Hyg 100:770–771, 2019; Int J Derm 39:856–858, 2000; scrofuloderma and tuberculosis verrucosa cutis Dermatology 196:459–460, 1998; scrofuloderma J Dermatol 22:582–586, 1995; erythema nodosum and tuberculous inguinal lymphadenitis Eur J Intern Med 16:531–533, 2005; Trans R Soc Trop Med Hyg 78:81–85, 1984 Onchocerciasis Paracoccidioidomycosis JAAD 53:931–951, 2005 Pneumococcal inguinal adenitis NY State J Med 85:509–510, 1985 Plague Streptococcal disease – Am J Med 77:151–153, 1984; group B streptococcal adenitis and cellulitis Arch Fr Pediatr 44:889, 1987

Epithelioid sarcoma – ankle ulcer, sporotrichoid nodules, and inguinal lymphadenopathy Acta Med Iran 48:72–74, 2010; Eur J Dermatol 13:599–602, 2003 Extramammary Paget’s disease Ned Tijdschr Geneeskd 163:D3381, 2019 Hodgkin’s disease Lymphoma- primary cutaneous B-cell lymphoma Int Wound J 13:1227–1230, 2016; angioimmunoblastic T-cell lymphoma Intern Med 56:85–89, 2017; angioimmunoblastic T-cell lymphoma and lupus-like malar rash Clin Case Rep 3:46–49, 2015; B-cell lymphoma – penile ulcer Dermatol Online J 11:29, 2005 Melanoma – of the heel Lymphat Res Biol 10:118–11, 2012; of the penis World J Surg Oncol Nov 11, 2014 Metastases – prostate cancer, penile nodule, and inguinal lymphadenopathy Indian J Urol 56–58, 2013 Myeloid sarcoma, inguinal lymphadenopathy, acute myelogenous leukemia Head Neck Pathol 11:219–223, 2017

Syphilis S Afr Med J 106; 49–51, 2016; Am J Surg Pathol 3:553– 555, 1979; necrotizing lymphadenitis NEJM 371:2511–2520, 2014; primary and secondary syphilitic balanitis of Follman Int J Dermatol 53:830–831, 2014

PRIMARY CUTANEOUS DISEASE

Toxoplasmosis S Afr Med J 60:784–785, 1981

Keratosis lichenoides chronica (Nekam’s disease) J Dermatol 34:41–47, 2007

Tularemia Ned Tjdschr Genecska 2017;160:D1180; Int Med Case Rep 11:313–318, 2018

Angiolymphoid hyperplasia with eosinophilia JAAD 43:698–700, 2000

Subcorneal pustular dermatosis BJD 119:803–807, 1988

West Nile virus BMJ Case Rep May 2, 2015 Whipple’s disease Ned Tijdschr Geneeskd 153:B497, 2009 Yersinia enterocolitica South Med J 82:401–402, 1989; Diagn Microbiol Infct Dis 5:265–268, 1986

SYNDROMES Lipodystrophia centrifugalis abdominalis infantilis J Cutan Med Surg 20:349–4351, 2016; J Dermatol 28:320–323, 2001 POEMS syndrome J Med Case Rep 27:384, 2019

INFILTRATIVE DISORDERS Langerhans cell histiocytosis, adult BMJ Case Rep Jan 10, 2018; Intern Med 54:1643–1646, 2015

TRAUMA

Rosai-Dorfman disease Int J Dermatol 41:404–406, 2002

Barefoot walking in Nigeria Acta Trop 42:87–96, 1985 Lymphocoele Indian J Urol 35:168–169, 2019

INFLAMMATORY CONDITIONS Dermatopathic lymphadenopathy – numerous dermatologic conditions Clin Nephrol 66:472–475, 2006 Hidradenitis suppurativa

Penile drug abuse Urology 45:686–688, 1995

SYNDROMES TAFRO syndrome with primary Sjogren’s syndrome Nihon Rinsho Meneki Gakkai Kaishi 39:478–484, 2016

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INTERTRIGO, INCLUDING DIAPER DERMATITIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – medicines, contraceptives, occupational exposure; topical corticosteroids AD 119:1023, 1983; systemic contact dermatitis to foods – flexural dermatitis, eyelid, genital, dyshidrosis Cutis 104:337–340, 2019; lichens – allergic contact dermatitis of axilla JAAD 55:332–337, 2006; benzalkonium chloride in antiseptic bath oil BJD 157:795–798, 2007; diaper dermatitis – allergic contact dermatitis to mercaptobenzothiazole Ped Derm 28:739–741, 2011; baboon syndrome due to caine cream for hemorrhoids Dermatitis 22:360–362, 2012; allergic contact dermatitis to methylisothiazolinone in laundry detergent – periaxillary nummular dermatitis Ped Derm 34:486–487, 2017 Bullous pemphigoid; localized childhood vulvar pemphigoid AD 128:804–807, 1992; JAAD 22:762–764; 1990; Ped Derm 2:302– 307, 1985 Cicatricial pemphigoid; BJD 118:209–217, 1988; Oral Surg 54:656–662, 1982

plaques and acral erythema; multiple chemotherapeutic agents including cytarabine, 5–fluorouracil, taxanes, anthracyclines, methotrexate JAAD 63:175–177, 2010 Arsenic trioxide – treatment for promyelocytic leukemia; flexural red papules JAMADerm 155:389–390, 2019 Baboon syndrome (symmetrical drug-related intertriginous and flexural exanthem) – Asian Pac J Allergy Immunol 29:150–160, 2011; Expert Rev Dermatol 4:163–175, 2009; Dermatology 214:1–2, 2007; Contact Derm 50:349–353, 2004; cetuximab (EGFR inhibitor); intertrigo with pustules AD 144:272–274, 2008; respiridone Ped Derm 26:214–216, 2009; amoxicillin/clavulanate Ped Derm 29:770–771, 2012; ceftazidime Ped Derm 33:345–346, 2016; intertriginous follicular purpura BJD 150:788–789, 2004 Bleomycin, intrapleural – personal observation Chemotherapy in children – intertriginous confluent dusky red patches healing with post-inflammatory hyperpigmentation and desquamation AD 143:67–71, 2007 Chemotherapy-related eccrine squamous syringometaplasia – red plaques of the neck, axillae, and groin; doxorubicin; bone marrow transplant regimen (cyclophosphamide, thiotepa, carboplatin) JAAD 64:1092–1103, 2011 Clindamycin BMJ Case Rep Aug 2, 2019

Dermatitis herpetiformis – diaper area

Corticosteroid atrophy, striae

Dermatomyositis – personal observation

Cytarabine – purpuric intertriginous plaques, scalp involvement, papules coalesce into papular purpuric violaceous generalized exanthema, red knee, red feet JAAD 73:821–828, 2015; toxic erythema of chemotherapy JAMADerm 727–728, 2016; malignant intertrigo CMAJ 190:E595, 2018

Epidermolysis bullosa acquisita IgA pemphigus – resembles subcorneal pustular dermatosis AD 138: 744–746, 2002; JAAD 43:546–549, 2000; antibodies to desmocollin 1,2,3 AD 145:1159–1162, 2009 Lichenoid reactions with antibodies to desmoplakins I and II – vulvar erythema and perianal erythema JAAD 48:433–438, 2003 Linear IgA disease (chronic bullous disease of childhood) – intertriginous and perigenital JAAD 51:95–98, 2004 Lupus erythematosus – discoid LE, neonatal LE, telangiectasias in neonatal LE Pemphigoid vegetans – vegetating plaque JAAD 30:649–650, 1994; JAAD 29:293–299, 1993; AD 115:446–448, 1979; concurrent pemphigus vegetans and pemphigoid vegetans – vegetative plaques of groin BJD 170:1192–1194, 2014 Pemphigus foliaceus – personal observation Pemphigus vegetans; AD 114:627–628, 1978; pemphigus vegetans, Neumann type – giant cobblestoning with vegetative intertriginous plaques and blisters; oral bullae AD 145:715–720, 2009; concurrent pemphigus vegetans and pemphigoid vegetans – vegetative plaques of groin Clin Dermatol 33:491–496, 2015; BJD 170:1192– 1194, 2014 Pemphigus vulgaris Cutis 61:21–24, 1998 Scleroderma – axillary verrucous pigmentation resembling acanthosis nigricans Br Med J ii:1642–1645, 1966

CONGENITAL LESIONS Congenital erosive and vesicular dermatosis with reticulate supple scarring – intertriginous bullae, erosions, and reticulate scarring JAAD 58:S104–106, 2008

DRUG Acral dysesthesia syndrome (chemotherapy–induced acral erythema) (toxic erythema of chemotherapy) – intertriginous eroded

Dactinomycin – flexural cutaneous necrosis with post-inflammatory hyperpigmentation; morbilliform, macular desquamative dermatitis, brawny erythema AD 142:1660–1661, 2006 Doxorubicin – polyethylene glycol-coated liposomal doxorubicin BJD 176:507–509, 2017; AD 136:1475–1480, 2000; periaxillary erythema – pegylated doxorubicin JAAD 58:S44–46, 2008; doxorubicin/daunorubicin – intertrigo JAAD 71:203–214, 2014 Efalizumab – intertriginous papular psoriasis AD 143:900–906, 2007 Etretinate ulcers of intertriginous areas Cutis 45:111–3, 1990 Everolimus – baboon syndrome Dermatitis 27:76–77, 2016 5-Fluorouracil, topical – baboon syndrome Cutis 89:225–228, 2012 Fixed drug eruption Dtsch Med Wochenschr 125:1260–1262, 2000 Ifosfamide – flexural pigmentation JAAD 71:203–214, 2014 Interleukin-1 alpha followed by ifosfamide, carboplatin, and etoposide – erosive intertrigo JAAD 35:705–709, 1996 Interstitial granulomatous drug reaction – red to violaceous annular plaques in skin folds, medial arms; calcium channel blockers, ACE inhibitors, beta blockers, lipid-lowering agents, antihistamines, anticonvulsants, antidepressants, diuretics, NSAIDS, sennoside, herbal medications Advances in Dermatol 22:31– 53, 2007; JAAD 52:712–713, 2005; J Cutan Pathol 25:72–78, 1998 Lithium carbonate – axillary subcorneal pustular dermatosis Cutis 41:165–166, 1988 Melphalan flexural dermatitis – personal observation Methotrexate or cyclophosphamide – baboon syndrome AD 143:67–71, 2007 Palifermin – flexural hyperpigmentation, papillomatosis, and erythema; also on elbows and knees AD 145:179–182, 2009; BJD 159:1200–1203, 2008

Intertrigo, Including Diaper Dermatitis 561 Pembrolizumab (anti-PD-1) – fiery red eroded inguinal intertrigo (baboon syndrome) JAMADerm 152:590–592, 2016

Trichophyton verrucosum (zoophilic fungus of cattle) diaper dermatitis Ped Derm 10:368–369, 1993

Periorificial dermatitis around vulva due to topical steroids

Diphtheria – superficial round ulcer with overhanging edge; gray adherent membrane; later edge thickens and becomes raised and rolled; umbilicus, post-auricular, groin, finger, or toe web; heals with scarring; crusts around the nose and mouth with faucial diphtheria Schweiz Rundsch Med Prax 87:1188–1190, 1998; Postgrad Med J 72:619–620, 1996; Am J Epidemiol 102:179–184, 1975

Pustular drug eruption – personal observation Syringosquamous metaplasia – red, blanching, crusted papules; due to cancer chemotherapy BJD 134:984–986, 1996; AD 126:73– 77, 1990; Am J Dermatopathol 12:1–6, 1990 Symmetric drug-related flexural exanthema (baboon syndrome) – amoxicillin Ped Derm 28:711–714, 2011 Terbinafine Int J Dermatol 56:100–103, 2017 Tumor necrosis factor alpha antagonists – lichen planus-like eruptions; gluteal intertrigo JAAD 61:104–111, 2009 Vancomycin – linear IgA dermatitis (personal observation)

EXOGENOUS AGENTS Benzocaine – erosive papulonodular dermatitis (granuloma gluteale infantum, pseudoverrucous papules, Jacquet’s erosive diaper dermatitis JAAD 55:S74–80, 2006 Irritant contact dermatitis – axillary dermatitis from deodorant sticks; irritant diaper (napkin) dermatitis, peristomal and perianal dermatitis Synthetic opioid MT-45 – painful intertrigo, folliculitis, dry eyes, hair depigmentation, hair loss, Mees’ lines, abnormal liver function tests BJD 176:1021–1027, 2017 Senneca laxative – blistering erosive diaper dermatitis; diamondshaped erosion of buttocks with linear borders aligning with diaper edge; spares perianal area and gluteal cleft AD 148:402–404, 2012; Pediatrics 107:178–179, 2001

INFECTIONS AND/OR INFESTATIONS Amebiasis – phagedenic necrosis, fistulae, pseudoelephantiasis; granulomas, condylomatous masses Dermatol Trop 2:129–136, 1963 Botryomycosis JAAD 9:428–434, 1983 Candidiasis – flexural candidiasis Clin Obstet Gynecol 24:407–438, 1981; diaper dermatitis; erosio interdigitalis blastomycetica and chronic mucocutaneous candidiasis; multiple entities can show changes of chronic mucocutaneous candidiasis including Nezelof syndrome, Swiss-type agammaglobulinemia, DiGeorge’s syndrome, hyper-IgE syndrome, mucoepithelial dysplasia Chancroid-resembling granuloma inguinale Chikungunya fever – in infants, starts with hyperpigmentation of the tip of the nose (chik sign), ear pinnae, flexures, periorally, then generalizes to the entire body; some vesiculobullous lesions JAMADerm 156:99–101, 2020 Condyloma acuminata Coxsackie A6 – generalized vesicular exanthema with flexural vesicles; acral purpuric macules of palms and soles Ped Derm 33:429–437, 2016; intertrigo, acral pustules and vesicopustules Cutis 102:353–356, 2018 Cytomegalovirus diaper dermatitis – a cause of perineal ulcers and diaper dermatitis AD 127: 396–398, 1991; JAAD 24:857–863, 1991 Dermatophilus congolensis – due to contact with infected animals BJD 145:170–171, 2001 Dermatophytosis – tinea corporis, tinea cruris – Trichophyton rubrum, Epidermophyton floccosum Semin Dermatol 4:185–200, 1985; tinea pedis – bullous Trichophyton rubrum and Epidermophyton diaper dermatitis Clin Ped 26:149–151, 1987;

Enterobiasis (Enterobius vermicularis) – perineal intertrigo Epstein-Barr virus and cytomegalovirus infection – baboon syndrome with purpuric papules of axillary folds, groin, gluteal crease Ped Derm, 2013 Erythrasma – intertriginous and perigenital; Corynebacterium minutissimum; red to brown irregularly shaped and sharply marginated scaly and slightly creased patches of the groin, axillae, intergluteal, submammary flexures, toe webs; coral-red fluorescence with Wood’s light examination due to coproporphyrin; toe clefts are most frequent location; acanthosis nigricans and normal follicular openings of the face and trunk may show coral pink fluorescence Rev Infect Dis 4:1220–1235, 1982 Folliculitis – inferior gluteal crease; bikini bottom Indian J Dermatol 62:66–78, 2017 Fusarium interdigitas Acta DV 99:835–836, 2019 Gram-negative web space infections JAAD 45:537–541, 2001; AD 141:658, 2005; JAAD 8:225–228, 1983 Granuloma inguinale – serpiginous ulceration in flexures with region LAD Clin Dermatol 33:420–428, 2015 Hand-foot-and-mouth disease – diaper rash of hand-foot-and-mouth disease Dialogues in Dermatol, Nov. 2001 Herpes simplex infection – knife-cut sign Clin Inf Dis 47:1440–1441, 2008 linear intertrigo HTLV-1 infection – infective dermatitis of the scalp, eyelid margins, perinasal skin, retro-auricular areas, axillae, groin; generalized papular dermatitis Semin Diag Pathol April 17, 2019; Lancet 336:1345–1347, 1990; BJD 79:229–236, 1967; BJD 78:93–100, 1966 Impetigo contagiosa – personal observation Molluscum contagiosum Mycobacterium haemophilum – inguinal ulcer AD 138:229–230, 2002 Mycobacterium tuberculosis – lupus vulgaris SKINmed 10:28–33, 2012; tuberculosis verrucosa cutis periorificial tuberculosis JAAD 51:492–493, 2003 North American blastomycosis Parvovirus B19 infection – accentuation in folds; periflexural purpuric eruption (baboon-like syndrome) JAAD 71:62–69, 2014 Pediculosis Pseudomonas – toe web space maceration and ulceration AD 107:71–74, 1973; blue underpants sign Recurrent toxin-mediated perineal erythema – associated with pharyngitis due to Staphylococcus aureus or Streptococcus pyogenes AD 144:2390243, 2008; AD 132:57060, 1996 Scabies, crusted – hyperkeratotic intertrigo, ears, scaly abdomen, and hand Cutis 94:86–88,95, 2014 Scarlet fever – perigenital dermatitis; Pastia’s lines Schistosomiasis – phagedenic necrosis, fistulae, pseudoelephantiasis; granulomas, condylomatous masses Seabather’s eruption – on Long Island, causative organism is the planula larvae of the sea anemone Edwardsiella lineata; in Florida,

562 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 planula larvae of the jellyfish Linuche unguiculata JAAD 30:269– 270, 1994; NEJM 329:542–544, 1993 Staphylococcus aureus pustulosis (folliculitis)

316, 2007; JAAD 55:185–187, 2006; NEJM 338:1138–1143, 1998; JAAD 23:341–346, 1990; AD Syphilol 37:373–402, 1938; multiple facial nodules flexural involvement JAAD 58:S47–49, 2008

Streptococcal intertrigo – neck in chubby babies Pediatrics 112:1427–1429, 2003; post-auricular area, groin, perianal cellulitis Ped Derm 24:577–578, 2007; BJD 74:323–325, 1962

Verrucous (verruciform) xanthoma – normolipemic; most commonly on mucosal surfaces, especially the oral mucosa; also nose, axilla, neck, and scalp AD 143:1067–1072, 2007

Syphilis – congenital, secondary – late secondary submammary lesions, interdigital toe lesions Clin Inf Dis 55:1106,1164–1166, 2012; secondary (noduloulcerative) (lues maligna) in AIDS Clin Inf Dis 25:1343, 1447, 1997; Treponema pallidum discovered by Schaudinn and Hoffmann in 1905 Tinea versicolor (Malassezia intertrigo) Mycoses 31:558–562, 1988 Trichomycosis axillaris Clin Dermatol 33:420–428, 2015 Unilateral laterothoracic exanthem – axillary fold with centrifugal spread

INFLAMMATORY DISORDERS Crohn’s disease – metastatic granulomatous nodules and ulcers, perianal extension with papules, nodules, ulcers, sinus tracts, and intertriginous ulcers, nodules, plaques, and knife-cut sign JAMADerm 154:609–610, 2018; JAAD 36:986–988, 1996; Gastroenterology 86:941–944, 1984 Psoriasiform dermatitis of Jadassohn

Varicella

Granuloma gluteale infantum – reddish-brown, purple nodules Ped Derm 17:141–143, 2000; AD 125:1703–1708, 1989; AD 111:1072– 1073, 1975; due to topical corticosteroids JAAD 54:1–15, 2006

Verruca vulgaris – toe web warts; HPV-7 BJD 174:678–681, 2016

Granuloma inframammary adultorum AD 150:1113–1114, 2014

Viral exanthems – accentuated or limited to diaper area

Hidradenitis suppurativa Derm Surg 26:638–643, 2000; BJD 141:231–239, 1999

Vaccinia – auto-inoculation vaccinia JAAD 50:139–141, 2004

Yaws

Post-inflammatory hyperpigmentation

INFILTRATIVE DISEASES

Pyoderma gangrenosum – ulcerative diaper dermatitis Ped Derm 11:10, 1994

Benign non-X histiocytosis JAAD 18:1289, 1988 Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100; xanthoma and xanthelasma-­like lesions (red-brown-yellow papules and plaques); flat wart-like papules of the face; lesions occur in folds; skin becomes slack with atrophy of folds and face; also lesions of the eyelids, axillae, groin, neck; bony lesions; diabetes insipidus, painless exophthalmos, retroperitoneal, renal, and pulmonary histiocytic infiltration JAAD 57:1031–1045, 2007; AD 143:952–953, 2007; Hautarzt 52:510–517, 2001; Medicine (Baltimore) 75:157– 169, 1996; Virchow Arch Pathol Anat 279:541–542, 1930 Juvenile xanthogranuloma JAAD 14:405–411, 1986 Langerhans cell histiocytosis – erosive intertrigo Clin Dermatol 38:223–234, 2020; JAAD 78:1035–1044, 2018; AD 145:949–950, 2009; eroded intertrigo of gluteal crease – adult LCH JAAD 65:681–683, 2011; intertriginous papules AD 146:149–156, 2010; cutaneous findings include crops of red-brown or red-yellow papules, vesicopustules, erosions, scaling, and seborrheic dermatitis-like papules, petechiae, purpura, solitary nodules AD 144:1287–1290, 2008; JAAD 56:302–316, 2007; AD 137:1241– 1246, 2001; Curr Prob Derm VI Jan/Feb 1994; Clin Exp Derm 11:183–187, 1986; JAAD 13:481–496, 1985; adult multisystem Langerhans cell histiocytosis – purpuric intertrigo AD 144:649–653, 2008; eroded submammary bright red plaques – adult Langerhans cell histiocytosis JAMADerm 150:1105–1106, 2014; in adult – ulcerated red plaque of groin Mastocytosis (urticaria pigmentosa) – flexural hyperpigmented reticulated plaques JAAD 55:347–349, 2006; AD 139:381–386, 2003; xanthelasmoid mastocytosis – flexural yellow papules and plaques Ped Derm 21:520, 2004; xanthelasmoidea AD 112:1270– 1271, 1976; Med Chir Trans 66:329–347, 1883 Xanthoma disseminatum (Montgomery’s syndrome) – intertriginous red-yellow-brown papules and nodules; become confluent into xanthomatous plaques; verrucous plaques; perioral papules; eyelid papules; scrotal papules; intertrigo; monoclonal gammopathy JAMADerm 154:721–722, 2018; JAMADerm 152:715–716, 2016; BJD 170:1177–1181, 2014; AD 147:459–464, 2011; JAAD 56:302–

METABOLIC Acrodermatitis enteropathica – psoriasiform dermatitis Ped Derm 27:395–396, 2010; acquired zinc deficiency Biotin deficiency (multiple carboxylase deficiencies) – psoriasiform, periorificial intertriginous dermatitis; diarrhea, alopecia Ped Derm 33:457–458, 2016; Clin in Dermatol 33:414–419, 2015; NEJM 304:820–823, 1981 Calcinosis cutis – calcified intertrigo Ann DV 122:789–792, 1995; JAAD 8:103–106, 1983; plaque-type intertriginous calcinosis cutis Cutis 49:289–291, 1992 Cystic fibrosis – diaper dermatitis AD 146:171–174, 2010 Essential fatty acid deficiency – severe xerosis with underlying erythema, hair loss with hypopigmentation, and weeping intertriginous rash Clin in Dermatol 33:413–419, 2015; Ped Derm 16:95– 102, 1999 Fabry’s disease – angiokeratomas yielding erythema of gluteal cleft BJD 166:712–720, 2012 Holocarboxylase synthetase deficiency – periorbital and periorificial erythema and/or dermatitis, intertriginous erythema Ped Derm 28:333–334, 2011 Kwashiorkor – crusting and superficial erosions in the diaper area AD 137:630–636, 2001; Ann DV 113:657–659, 1977 Maple syrup urine disease Metabolic syndrome – personal observation Miliaria Multiple carboxylase deficiency (biotin-responsive) – pyruvate carboxylase, propionyl-coenzyme A carboxylase, and 3-methylcrotohyl-­CoA carboxylase; accumulation of urinary organic acids; neonatal – holocarboxylase synthetase deficiency; juvenile or late-onset from – biotinidase deficiency – erythematous scaly eruption interdigital webs, groin, axillae Ped Derm 21:231–235, 2004; Am J Med Genet 111:10–18, 2002; Ped Derm 16:95–102, 1999; Adv Pediatr 38:1–21, 1991; AD 123:1696–1698, 1987

Intertrigo, Including Diaper Dermatitis 563 Pyoderma vegetans – vegetative plaques of intertriginous areas; associated with ulcerative colitis JAAD 75:578–584, 2016 Riboflavin deficiency – component of coenzymes flavin mononucleotide and flavin-adenine dinucleotide involved in oxidative phosphorylation; deficiency produces dermatitis similar to glucagonoma syndrome with a prominent periorificial component; angular stomatitis which often bleeds, vertical fissuring of the lips, smooth magenta tongue, seborrheic dermatitis-like rash, scrotal dermatitis; riboflavin deficiency seen in hypothyroidism, acute boric acid ingestion, chlorpromazine use and neonatal phototherapy for hyperbilirubinemia JAAD 68:211–243, 2013; Semin Derm 10:293– 295, 1991; JAAD 21:1–30, 1989

PARANEOPLASTIC Acanthosis nigricans Clin in Dermatol 33:462–465, 2015; BJD 153:667–668, 2005 Glucagonoma syndrome (necrolytic migratory erythema) – erosive intertrigo JAMADerm 345–347, 2016; AD 144:795–800, 2008; AD 45:1069–1080, 1942 Paraneoplastic annular erythema – perigenital dermatitis Skin spicules – paraneoplastic intertriginous filiform seborrheic keratoses associated with marginal zone B-cell lymphoma JAAD 60:852–855, 2009

Xanthomas, eruptive Zinc deficiency – fiery red intertrigo AD 148:961–963, 2012; acquired zinc deficiency – intertrigo of gluteal crease JAMA Derm 149:357–362, 2013

NEOPLASTIC Acrochordons with acanthosis nigricans Apocrine adenocarcinoma, metastatic – red plaque of axilla JAMADerm 152:111–113, 2016 Basal cell carcinoma – red plaque in inguinal crease; shiny pink axillary plaque Derm Surg 27:966–968, 2001 Bowen’s disease Bowenoid papulosis – personal observation Epidermal nevus – intertriginous and perigenital Extramammary Paget’s disease – the clinical picture of Paget’s disease may change daily and may even become subclinical; underlying adnexal carcinoma or carcinoma of the rectum, urethra, cervix, or distant carcinoma of the breast JAAD 51:492–493, 2003; Sem Cut Med Surg 21:159–165, 2002; unilateral axillary Paget’s disease J Dermatol 25:260–263, 1998; Plast Reconstr Surg 100:336–339, 1997; AD 127:1243, 1991; red plaque of inguinal crease and scrotum BJD 153:676–677, 2005 ILVEN – intertriginous and perigenital; red plaque of the penis and scrotum and intertrigo Cutis 94:35–38, 2014 Kaposi’s sarcoma

PRIMARY CUTANEOUS DISEASE Acantholytic dermatosis of the vulvo-crural area (papular acantholytic dermatosis) – vulvar papules, cobblestoning of the vulva and thighs Cutis 67:217–219, 2001; Am J Dermatopathol 6:557–560, 1984 Acanthosis nigricans – velvety plaques, intertriginous pigmentation; unilateral nevoid acanthosis nigricans – may be epidermal nevus resembling acanthosis nigricans; axillary (dark intertrigo) BJD 179:1001–1002, 2018; JAAD 58:S102–103, 2008; unilateral JAAD Case Rep 5:132–134, 2016 Acquired epidermodysplasia verruciformis – personal observation Amicrobial pustulosis – exudative erythema, erosions, pustules, diffuse alopecia with dermatitis; associated with systemic autoimmune disorders; scalp, axillae, ears, thighs JAAD 57:523–526, 2007; BJD 154:568–569, 2006; Communication no.11. Journees Dermatologiques de Paris, March 1991. Atopic dermatitis Axillary acne agminata – axillary red papules (form of granulomatous rosacea) JAMADerm 151:893–894, 2015 Axillary granular parakeratosis JAAD 24:541–544, 1991 Bromhidrosis Clin Dermatol 33:483–491, 2015 Childhood flexural comedones – double opening AD 143:909–911, 2007 Chromhidrosis Clin Dermatol 33:483–491, 2015

Keratoacanthomas of Grzybowski – personal observation

Confluent and reticulated papillomatosis – velvety plaques, intertriginous pigmentation (personal observation)

Lentiginosis profusa – intertriginous pigmentation

Cutis laxa

Lymphoma – cutaneous T-cell lymphoma with axillary intertrigo; poikiloderma vasculare atrophicans with CTCL; granulomatous slack skin syndrome (cutaneous T-cell lymphoma) BJD 157:405– 407, 2007; CTCL – malignant follicular helper T cells AD 148:1040– 1044, 2012

Darier’s disease – autosomal dominant; intertriginous pigmentation; photo-aggravated in seborrheic distribution; skin colored, brown, yellow-brown papules which may coalesce into verrucous plaques or papillomatous masses; acrokeratosis verruciformis of Hopf, palmar and plantar pits, cobblestoned mucous membranes Clin in Dermatol 33:448–451, 2015

Melanoma JAAD 51:492–493, 2003 Metastatic gastric carcinoma – condyloma-like lesions in the axilla and groin Pathology of Unusual Malignant Cutaneous Tumors, New York, Marcel Dekker pp.357–397, 1985 Porokeratosis (porokeratosis ptychotropica) – hyperpigmented verrucous plaques of intertriginous areas JAMA Derm 149:1099– 1100, 2013; AD 146:911–916, 2010; JAAD 60:501–503, 2009; JAAD 55:S120–122, 2006; Cutis 72:391–393, 2003; Clin Exp Dermatol 28:450–452, 2003; BJD 140:553–555, 1999; BJD 132:150–151, 1995 Primary cutaneous adenoid cystic carcinoma – violaceous nodule of the groin JAMA Derm 149:1343–1344, 2013 Syringomas

Dermatosparaxis in children – groin fissures AD 129:131–1315, 1993 Diaper dermatitis with rapid dissemination – expanding nummular dermatitis of the trunk, and red scaly plaques of the neck and axillae (“psoriasiform id”) BJD 78:289–296, 1966; napkin psoriasis, napkin dermatitis Clin in Dermatol 33:477–482, 2015 Dowling-Degos disease – velvety plaques and intertriginous pigmentation – mutations in KRT5/POFUT1 (protein-O-fucosyl transferase) POGLUT1 BJD 177:945–959, 2017; BJD 173:584–586, 2015; AD 114:1150–1157, 1978; AD 114:1150–1157, 1976 Eccrine squamous syringometaplasia – red plaques in axillae and groin AD 133:873–878, 1997 Elastosis perforans serpiginosa with pseudoxanthoma elasticumlike changes in Moya-Moya disease (bilateral stenosis and

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occlusion of basa intracranial vessels and carotid arteries) BJD 153:431–434, 2005

Interstitial granulomatous dermatitis – axillary folds and groin; may be drug-induced BJD 150:1035–1037, 2004

Epidermolysis bullosa atrophicans inversa (dermolytic dystrophic)

Kitamura’s disease – intertriginous pigmentation

Epidermolysis bullosa inversa – early generalized involvement with blisters and erosions healing with superficial atrophic scars persisting into adulthood; blisters of the trunk, proximal extremities, including the axillae, groin, and perineum; form of junctional epidermolysis bullosa with oral blisters, dysplastic teeth, dystrophic toenails with normal fingernails, hoarseness, corneal erosions, and albostriate lesions JAAD 12:836–844, 1985; AD 124:544–547, 1988

Leiner’s disease

Epidermolysis bullosa – junctional epidermolysis bullosa, Herlitz type – erosive diaper dermatitis Ped Derm 14:307–311, 1997 Epidermolysis bullosa simplex – migratory circinate erythema of axilla Ped Derm 37:358–361, 2020 Epidermolytic ichthyosis – personal observation Erythema annulare centrifugum Erythema of Jacquet (erosive papulonodular dermatosis) – erosive diaper dermatitis; shallow, round ulcers with raised edges; umbilicated papules, erosions BJD 158:413–414, 2008; Ped Derm 15:46–47, 1998 Erythrokeratodermia variabilis Fox-Fordyce disease Galli-Galli disease – acantholytic variation of Dowling-Degos disease; reticulated hyperpigmentation with red macules, papules, and papulovesicles AD 147:317–320, 2011; BJD 163:197–200, 2010; JAAD 58:299–302, 2008; BJD 150:350–352, 2004; JAAD 45:760–763, 2001; Akt Dermatol 12:41–46, 1986; Hautarzt 33:378–383, 1982; reticulate, hyper– and hypopigmented macules and papules; intertrigo; mutation in keratin 5 BJD 170:1362–1365, 2014 Granular parakeratosis – hyperkeratotic papules and plaques in the intertriginous areas in children (infantile granular parakeratosis) JAAD 52:863–867, 2005; JAAD 50S93–96, 2004; BJD 147:1003– 1006, 2002; Ped Derm 19:146–147, 2002; axillary (or submammary) granular hyperkeratosis (axillary granular parakeratosis) – unilateral or bilateral pruritic erythematous or hyperpigmented gray-brown patches or plaques; punctate hyperkeratosis; keratohyalin granules are retained in the markedly thickened stratum corneum AD 147:997–998, 2011; AD 144:1651– 1656, 2008; JAAD 58:S84–87, 2008; Cutis 80:55–56, 2007; AD 140:1161–1166, 2004;JAAD 47:S279–280, 2002; AD 137:1241– 1246, 2001; JAAD 40:813–814, 1999; JAAD 39:495–496, 1998; JAAD 37:789–790, 1997; JAAD 33:373–375, 1995; JAAD 24:541– 544, 1991 Granuloma gluteale infantum – nodules in intertriginous areas under diaper; due to topical corticosteroids JAAD 54:1–15, 2006 Granuloma inframammary adultorum – following topical corticosteroid therapy JAMADerm 150:1113–1115, 2014 Greither’s palmoplantar keratoderma – linear axillary hyperkeratosis; hyperkeratosis of elbows, knees, shins JAAD 53:S225–230, 2005 Grover’s disease – personal observation

Lichen planus – inverse lichen planus; violaceous patches of axilla JAMADerm 154:1477–1478, 2018; SKINMed 11:355–356, 2013; lichen planus pigmentosus inversus – linear gray-brown macules of intertriginous areas in folds of the chest, abdomen, and groin AD 147:1097–1102, 2011; JAAD 60:359–375, 2009 Lichen sclerosus et atrophicus – generalized extragenital lichen sclerosus et atrophicus – white plaques; intertriginous distribution; bullae Clin Exp Dermatol 45:498–500, 2020; AD 145:1303–1308, 2009; axillary Cutis 69:285–287, 2002 Lichen simplex chronicus Lupus miliaris disseminatus faciei (acne agminata) – axillary Clin Exp Dermatol 23:125–128, 1998 Miliaria rubra in infants – red papular eruption of the neck, axilla, groin BJD 99:117–137, 1978 Napkin psoriasis – personal observation Non-bullous CIE (congenital ichthyosiform erythroderma) (erythrodermic lamellar ichthyosis) – autosomal recessive – intertrigo-like pattern AD 121:477–488, 1985 Papillary dermal elastolysis – flexural PXE-like changes; decreased oxytalan and elaunin elastic fibers J Cutan Pathol 36:1010–1013, 2009; J Dermatol 34:709–711, 2007; JAAD 51:958, 2004; JAAD 51:165–185, 2004; J Eur Acad Dermatol Venereol 51: 175–178, 2004 Pityriasis rosea Pityriasis rubra pilaris, juvenile – psoriasiform dermatitis of gluteal crease JAAD 59:943–948, 2008 Poikiloderma vasculare atrophicans Progressive symmetric erythrokeratodermia – intertriginous and perigenital; must be differentiated from erythrokeratodermia variabilis (migrating erythematous patches) and localized forms of pityriasis rubra pilaris AD 122:434–440, 1986 Prurigo pigmentosa – flexural reticulated blue-gray pigmentation JAMADerm 155:377–378, 2019 Psoriasis AD 147:629–630, 2011; napkin psoriasis; inverse psoriasis Contact Dermatitis 26:248–252, 1992; BJD 773:445–447, 1961; intertriginous pustular psoriasis of childhood JAAD 60:679– 683, 2009 Pyoderma vegetans AD 116:1169–1171, 1980 Seborrheic dermatitis Subcorneal pustular dermatosis of Sneddon-Wilkinson – pustules which expand to annular and serpiginous lesions with scaly edge; heal with hyperpigmentation Ped Derm 20:57–59, 2003; BJD 145:852–854, 2001; J Dermatol 27:669–672, 2000; Cutis 61:203– 208, 1998; JAAD 19:854–858, 1988; BJD 68:385–394, 1956; resembles IgA pemphigus JAAD 43:546–549, 2000; Cutis 61:225– 226, 1998

Hailey-Hailey disease JAMA 319:1499–1500, 2018; JAMADerm 151:328–329, 2015; Clin in Dermatol 33:452–455, 2015; BJD 170:209–211, 2014; BJD 161:967–968, 2009; BJD 158:831–833, 2008; JID 126:2370–2376, 2006; BJD 126:275–282, 1992; Arch Dermatol Syphilol 39:679–685, 1939

Sybert keratoderma – autosomal dominant; palmoplantar erythema with transgrediens distribution, intertriginous hyperkeratosis, pseudoainhum with spontaneous amputations JAAD 18:75–86, 1988

Impetigo herpetiformis (pustular psoriasis of pregnancy) – symmetrical and grouped lesions, starting in flexures (inguinocrural areas) AD 136:1055–1060, 2000; AD 127:91–95, 1996; Acta Obstet Gynecol Scand 74:229–232, 1995

Transient neonatal pustular melanosis – diaper area

Terra firme

Intertrigo, Including Diaper Dermatitis 565

SYNDROMES Ankyloblepharon, ectodermal dysplasia, cleft lip/palate with ectrodactyly (AEC) syndrome – erosive diaper dermatitis; diffuse erythema with fine scaling and shallow erosions; no scalp hair or eyebrows or eyelashes; ectropion and ankyloblepharon; low-set ears, broad and beaked nose; downturned mouth; ectrodactyly of the right foot, choanal stenosis; erosive scalp and diaper dermatitis Ped Derm 28:313–317, 2011; Ped Derm 28:15–19, 2011 Conradi-Hunermann syndrome – hyperkeratosis in axillae AD 127:539–542, 1942 CHILD syndrome (prominence in body folds) – ptychotropism – preferential distribution in skin folds JAAD 23:763–766, 1990 Dowling-Degos syndrome (reticulated pigmented anomaly of the flexures) – reticulated pigmentation of axillae, groin, and other intertriginous areas, freckles of the vulva, comedo-like lesions, pitted scars around the mouth JAAD 40:462–467, 1999; Clin Exp Dermatol 9:439–350, 1984 Epidermodysplasia verruciformis – psoriasiform groin intertrigo AD 138:527–532, 2002 Fanconi’s anemia – autosomal recessive; endocrine abnormalities with hypothyroidism, decreased growth hormone, diabetes mellitus, café au lait macules, diffuse hyperpigmented macules, guttate hypopigmented macules, intertriginous hyperpigmentation, skeletal anomalies (thumb hypoplasia, absent thumbs, radii, carpal bones), oral/genital erythroplasia with development of squamous cell carcinoma, hepatic tumors, microphthalmia, ectopic or horseshoe kidney, broad nose, epicanthal folds, micrognathia, bone marrow failure, acute myelogenous leukemia, solid organ malignancies JAAD 54:1056–1059, 2006 Glucagonoma syndrome (necrolytic migratory erythema) – syndrome of weight loss, smooth tongue, periorificial, perigenital, and intertriginous rash; glucagon levels of 700–7000pg/ml (normal is 50–150 pg/ml) Haber’s syndrome – intertriginous pigmentation Hereditary mucoepithelial dysplasia (dyskeratosis) (gap junction disease, Witkop disease) – autosomal dominant; non-scarring alopecia; dry rough skin; red eyes, non-scarring alopecia, follicular keratosis (keratosis pilaris), erythema of oral (hard palate, gingival, tongue), and nasal mucous membranes, cervix, vagina, and urethra; perineal and perigenital psoriasiform dermatitis (perineal erythema); hyperpigmented hyperkeratotic lesions of flexures (neck, antecubital, and popliteal fossae); esophageal stenosis; keratitis (visual impairment) increased risk of infections, fibrocystic lung disease Ped Derm 29:311–315, 2012; BJD 153:310–318, 2005; Ped Derm 11:133–138, 1994; Am J Med Genet 39:338–341, 1991; JAAD 21:351–357, 1989; Am J Hum Genet 31:414–427, 1979; Oral Surg Oral Med Oral Pathol 46:645–657, 1978 Hyper IgE syndrome (Job’s syndrome) (Buckley’s syndrome) – autosomal dominant; papular, pustular, excoriated dermatitis of the scalp, buttocks, neck, axillae, groin; furunculosis; growth failure; dermatitis of the face, behind ears, scalp, axillae, and groin; recurrent bacterial infections of the skin with cold abscesses, contact urticaria, infections of nasal sinuses, and respiratory tract; atopic dermatitislike; oral candidiasis; diaper dermatitis Ped Derm 30:621–622, 2013; J Pediatr 141:572–575, 2002; NEJM 340:692–702, 1999; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983; Lancet 1:1013–1015, 1966

sis, intertriginous hyperpigmentation, and hyperkeratotic plaques in the adult JAMADerm 152:1055–1058, 2016 Incontinentia pigmenti – hyperpigmentation of axillae and groin JAAD 47:169–187, 2002 Kawasaki’s disease Keratitis ichthyosis deafness syndrome – exaggerated diaper dermatitis Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990 Lipoid proteinosis Netherton’s syndrome – intertriginous and perigenital dermatitis, edema, papillomatosis resembling cellulitis BJD 131:615–621, 1994; JAAD 13:329–337, 1985 Neurofibromatosis type I – Crowe’s sign – intertriginous pigmentation Olmsted syndrome – follicular hyperkeratosis of buttocks and knees; follicular papules; intertrigo, mutilating palmoplantar keratoderma, linear streaky hyperkeratosis, leukokeratosis of the tongue, sparse hair anteriorly JAAD 53:S266–272, 2005; Ped Derm 21:603–605, 2004; Ped Derm 20:323–326, 2003; Eur J Derm 13:524–528, 2003; BJD 136:935–938, 1997; AD 132:797–800, 1996; AD 131:738–739, 1995; Semin Derm 14:145–151, 1995; JAAD 10:600–610, 1984; Am J Dis Child 33:757–764, 1927 Pseudoxanthoma elasticum – linear and reticulated yellow papules and plaques JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; AD 124:1559, 1988 Reactive arthritis with keratoderma blenorrhagicum – personal observation Sjogren-Larsson syndrome – ichthyosis, mental retardation, spastic diplegia, short stature, kyphoscoliosis, retinal changes, yellow pigmentation, intertrigo (flexural accentuation), deficiency of fatty aldehyde dehydrogenase Ped Derm 20: 179–180, 2003; JAAD 35:678–684, 1996 Sweet’s syndrome Wiskott-Aldrich syndrome – dermatitis of the scalp, face, flexures, napkin area with petechiae and purpura; Xp11.22–11.23; WASP gene – actin polymerization Ped Derm 24:417–418, 2007; Cell Mol Life Sci 61:2361–2385, 2004; Semin Hematol 35:332–345, 1998; J Pediatr 125:876–885, 1994; Int J Dermatol 24:77–81, 1985 Xeroderma pigmentosum – intertriginous pigmentation X-linked (male) ectodermal dysplasia with immunodeficiency – NEMO mutation – widespread intertriginous dermatoses progressing to exfoliative erythroderma, alopecia, red scaly scalp, frontal bossing, periorbital wrinkling AD 144:342–346, 2008; Curr Opin Allergy Clin Immunol 5:513–518, 2005; Immunol Rev 203:21–37, 2005; J Pediatr 114:600–602, 1989

TOXIC Arsenic poisoning – acute; baboon syndrome (anogenital intertrigo) with intertriginous exanthem BJD 149:757–762, 2003 Methyl bromide fumigation – bullae and urticaria AD 127:917–921, 1991

TRAUMATIC Child abuse

Hyper IgM syndrome – diaper area ulcers Ped Derm 18:48–50, 2001

Friction and bacterial infection

Ichthyosis prematurity syndrome – hyperkeratotic cobblestoning of the back of the neck, flexural hyperpigmented follicular hyperkerato-

Runner’s rump (intertriginous hyperpigmentation) JAAD 21:1257– 1262, 1989

566 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

IRIS LESIONS, PIGMENTED

Melanosis oculi (iris nevus) AD 142:1243–1244, 2006; Metastatic melanoma AD 142:1243–1244, 2006

 UTOIMMUNE DISORDERS AND DISEASES A OF IMMUNE DYSFUNCTION

Nevus of Ota Dermatol Clin 10:609–622, 1992

Scleroderma – periorbital linear scleroderma associated with heterochromia iridis Am J Ophthalmol 90:858–861, 1980

DRUG REACTIONS

Pigmented episcleral spot (Axenfeld’s nerve loop) Primary acquired melanosis

SYNDROMES Aniridia with chromosome 18 defects

Prostaglandin analog – iris heterochromia and unilateral trichomegaly JAMA 313:1967–1968, 2015

Cat eye syndrome – iris coloboma with trisomy 22

EXOGENOUS AGENTS

Goltz’s syndrome – iris colobomas Ped Derm 31:220–224, 2014

AD 142:1243–1244, 2006

INFECTIONS AND INFESTATIONS Leprosy – leproma Metastatic infection Invest Ophthalmol and Visual Science 43:4262, 2002 Syphilis – papular of secondary or tertiary lues Am J Ophthalmol 90:380–384, 1980 Tuberculosis Surv Ophthalmol 38:229–256, 1993

INFILTRATIVE DISEASES Juvenile xanthogranuloma – iris heterochromia Eye and Skin Disease, pp.56–57, Lippincott, 1996

INFLAMMATORY DISEASES Sarcoidosis iris granuloma Clin Dermatol 4:129–135, 1986

Down’s syndrome – hypoplastic iris with lighter areas in the outer third (Brushfield spots) Incontinentia pigmenti – conjunctival pigmentation JAAD 47:169– 187, 2002 Iris coloboma   4p deletion syndromes   Cat eye syndrome   Chromosome 18 defects (including trisomy 18)   Focal dermal hypoplasia   Linear nevus sebaceus syndrome   Trisomy 22 Iris nevus syndrome (Cogan–Reese syndrome) Nail patella syndrome – cloverleaf iris (Lester iris); heterochromia iridis JAAD 74:231–244, 2016 Neurofibromatosis – Lisch nodule – yellow to brown elevations; predilection for inferior aspect of the iris JAAD 61:1–14, 2009; AD 142:1243–1244, 2006; NEJM 343:1573, 2000; NEJM 324:1264– 1266, 1991; J Med Genet 26:712–721, 1989; Am J Ophthalmol 96:740–742, 1983 Romberg’s syndrome – heterochromia iridis Am J Ophthalmol 90:858–861, 1980 Tuberous sclerosis – hypopigmented spots of the iris Ophthalmology 89:1155–1159, 1982 Vogt-Koyanagi-Harada syndrome

METABOLIC DISORDERS Band keratopathy (calcium in limbus) – personal observation Wilson’s disease Kayser-Fleischer rings; copper deposition in Descemet’s membrane

NEOPLASTIC DISEASES

Ziprkowski-Margolis syndrome – X-linked recessive, deaf-mutism, heterochromia iridis, piebald-like hypomelanosis JAAD 48:466–468, 2003

ISLANDS OF SPARING

Aniridia associated with Wilms’ tumor

AUTOIMMUNE DISEASES

Benign epithelial melanosis

Dermatomyositis, Wong type Dermatopathology(Basel)2:1–8, 2015

Conjunctival nevus Heterochromia iridis Iris cyst AD 142:1243–1244, 2006 Iris freckles AD 142:1243–1244, 2006 Iris metastases – breast, lung, kidney, melanoma Aurv Ophthalmol 62: 366–370, 2017; Oman J Ophthalmol 6:159–164 2013

Epidermolysis bullosa acquisita – erythroderma with islands of sparing JAMADerm 151:678–680, 2015 Parthenium dermatitis – deck chair sign JAMADerm 151:906–907, 2015

Leiomyoma

DRUG REACTIONS

Melanocytic nevus AD 142:1243–1244, 2006

Cefepime drug exanthem Cutis 89:173–174, 2012

Melanocytoma AD 142:1243–1244, 2006 Melanoma AD 142:1243–1244, 2006; AD 139:1067–1073, 2003

Morbilliform drug rash overlying nevus anemicus JAAD Case Rep 4:615–617, 2018

Islands of Sparing 567 MEK inhibitors (selumetinib, cobimetinib, trametinib) – hypersensitivity reactions JAMADerm 151:78–81, 2015 Methotrexate photorecall – personal observation

INFECTIONS AND INFESTATIONS Chikungunya fever – morbilliform exanthem of trunk and limbs with islands of sparing; high fever, headache, photophobia, myalgia, arthralgias, and arthritis of large joints with periarticular erythema NEJM 372:1657–1664, 2015; JAMADerm 151:257–258, 2015; Clin Inf Dis 20:225–231, 1995 Covid-19 JAAD 82:e177, 2020 Dengue hemorrhagic fever JAAD 48:430–433, 2002; hyperpigmentation of the nose (chik sign); transient flushing, purpuric lesions, scleral injection, morbilliform exanthem with circular islands of sparing, aphthous ulcers, lichenoid papules, flagellated pigmentation, urticarial lesions, erythema multiforme-like Ped Derm 36:737–739, 2019; Indian Dermatol Online J 8:336–342, 2017; JAAD 58:308–316, 2008; Indian J DV Leprol 76:671–676, 2010 Leprosy – borderline leprosy – “Swiss cheese” lesions; infiltrated plaques with normal skin in center Clinics in Dermatol 33:8–18, 2015; drug rash in Hansen’s disease Int J Dermatol 56:e102–104, 2017; deck chair sign Indian Dermatol Online J 6:204–206, 2015 Polyoma virus-7 rash – and pruritus in lung transplant recipient Transpl Infec Dis 20:e12793, 2018

INFILTRATIVE DISORDERS Lichen myxedematosus – personal observation Scleromyxedema – personal observation

INFLAMMATORY DISORDERS Erythema multiforme – due to telaprevir

NEOPLASTIC DISORDERS Cutaneous T-cell lymphoma

PRIMARY CUTANEOUS DISEASES Ichthyosis en confetti (ichthyosis variegata) – reticulated erythroderma with guttate hypopigmentation, palmoplantar keratoderma; loss of dermatoglyphics; temporary hypertrichosis of normal skin JAMADerm 151:15–16,64–69, 2015; BJD 166:434–439, 2012; JAAD 63:607–641, 2010; Acta DV 83:36–39, 2003; BJD 139:843– 846, 1998; Dermatology 188:40–45, 1994; Ann Dermatol Venereol 111:675–676, 1984; Hautarzt 35:522–529, 1984 Papuloerythroderma of Ofuji – deck chair sign J Eur Acad DV May 2, 2020 doi:10.1111/jdv.16581; Semin Diagn Pathol 36:211–228, 2019; Case Rep Dermatol 10:46–54, 2018 Pityriasis rubra pilaris; familial pityriasis rubra pilaris – erythroderma with islands of sparing; CARD14 gain-of-function mutation Am J Clin Dermatol 19:377–390, 2018; BJD 171:420–422, 2014 Spotty ichthyosis

SYNDROMES CHIME syndrome – colobomata, heart defects, ichthyosiform dermatosis of the flexures, mental retardation, and ear defects – congenital ichthyosis with islands of sparing; migratory plaques Curr Prob Derm 14:71–116, 2002; JAAD 46:S156–158, 2002; Ped Derm 18:252–254, 2001; J Med Genet 32:465–469, 1995 CRIE (congenital reticular ichthyosiform erythroderma) syndrome JAMADerm 151:15–16,64–69, 2015; BJD 166:434–439, 2012; JAAD 63:607–641, 2010; Acta DV 83:36–39, 2003; BJD 139:843– 846, 1998; Dermatology 188:40–45, 1994; Ann Dermatol Venereol 111:675–676, 1984; Hautarzt 35:522–529, 1984 MAUIE (micropinnae, alopecia universalis, congenital erythroderma, ectropion) syndrome JAMADerm 151:15–16,64–69, 2015

 APOSI’S SARCOMA, DIFFERENTIAL K DIAGNOSIS

Metastases, including hypernephroma (renal cell carcinoma), thyroid carcinoma Arch Craniofac Surg 20:3926, 2019 Primary cutaneous blastic plasmacytoid dendritic cell neoplasm Pathol Res Pract 207:55–59, 2011

VASCULAR TUMORS Benign  Acroangiodermatitis (pseudo-Kaposi’s sarcoma) – associated with AV malformation (congenital dysplastic angiopathy) AD 111:1656, 1975; AD 110:907, 1974; AD 100:297, 1969; associated with chronic venous insufficiency AD 92:515, 1965; AD 96:176, 1967   Angiokeratoma Annals Int Med 96:6693, 1982    Blue rubber bleb  Eccrine spiradenomas of the scalp Ann Chir Pkst Esthet 61:65–68, 2016  Glomus Minerva Stomatol 54:687–690, 2005; extradigital Indian J Dermatol 61:118, 2016  Hemangioma Cutis 7:401, 1971; cavernous; spindle cell Case Rep Med 2013:959812 doi:10.1155/2013/959812; microvenular hemangioma Oncol Letter 7:275–277, 2014; hobnail hemangioma Pol J Pathol 63:189–92, 2012  Intravascular papillary endothelial hyperplasia (Masson’s tumor) Diagn Pathol 8:167, Oct, 2013  Lymphangioma Bluefarb   Multinucleate cell angiohistiocytoma J Cut Pathol 46:59–61, 2019   Papular angioplasia Arch Derm vol 79:17–31, 1959  Pyogenic granuloma J Am Pod Med Assoc 105:195–197, 2015; Cutis 7:401, 1971  Reactive angioendotheliomatosis Cesk Patol 40:162–166, 2004; Arch Derm Vol 114:1512, 1978   Targetoid hemosiderotic hemangioma JAAD 19:550–558, 1988   Tufted hemangioma Dermatol Pract Concept 4:33–35, 2014 Malignant  Angiosarcomas in lymphedema Cutis 7:401, 1971; Arch Derm 111:86, 1975; angiosarcoma of the scalp Dermatol Online J May 15, 2019;13030/qt93s821d7   CD56+ myeloid sarcoma Oncol Lett 11:3091–3096, 2016  Hemangiopericytoma Arch Derm 116:806, 1980  Malignant angioendotheliomatosis Arch Derm 104:320, 1971; Arch Derm 84:22, 1961   Merkel cell carcinoma Przegl Lek 72:83:86, 2015   Plasmablastic lymphoma Dermatol Online J May 15, 2016

INFECTIOUS DISEASES Alternariosis, cutaneous Lupus 16:993–996, 2007 Bacillary angiomatosis J Int Assoc Proviers AIDS Care 14:21–25, 2015; Ann Int Med 109:449, 1988; JAMA 260:524, 1988 Buruli ulcer Disseminated BCG infection; X-linked severe combined immunodeficiency Ann DV 135:587–590, 2008 Fusarium, disseminated in acute lymphoblastic leukemia Medicine 92:e16246, 2019 Leishmaniasis in AIDS BJD 143:1316–1318, 2000 Leprosy, histoid Int J Dermatol 45:433–434, 2006 Majocchi’s granuloma (dermatophyte) Case Rep Dermatol Med 2014;507176 Mycetoma (Madura foot) Mycobacterium marinum Vet Q 38:35–46, 2018 Mycobacterium tuberculosis Orf Am J Dermatopathol 38:793–801, 2016 Syphilis, secondary – nodular Acta DV Croat 26:186–188, 2018; Int J Dermatol 53:e71–73, 2014; Eur J Dermatol 23:120–121, 2013

OTHERS Atrophie blanche JAAD 6:463, 1983 Chilblains Dermatol Online J 17:16, 2011 Cirsoid aneurysm of the forehead Indian J Dermatol 60:423, 2015 Coumadin – purple toe syndrome Cutis 6:639, 1971 Cryoproteinemia JAAD 27:969, 1992 Dermatofibroma Cutis 7:401, 1971 Ecchymoses Ann Int Med 96:693, 1982 Epidermoid cyst with hemorrhage

OTHER TUMORS

Fixed drug eruption – dapsone Expert Rev Clin Pharmacol 10:717–725, 2017

Acral pseudolymphomatous angiokeratoma of children (APACHE) Pathol Oncol Res 17:843–851, 2011

Hypertrophic port wine stain Zhonghua Bing Li Xue Za Ahi 48:878–883, 2019

Aneurysmal dermatofibroma Rom J Morph Embryol 55:1221–1224, 2014

Insect bites, necrotic Ann Int Med 96:693, 1992

Basal cell carcinoma, pigmented

Lichen planus, hypertrophic Arch Derm Syph 33:913, 1936; Arch Derm Syph 49:295, 1944

Cutaneous T-cell lymphoma

Lichen planus-like keratosis Indian J Dermatol 60:523, 2015

Fibrosarcoma/spindle cell sarcoma

Marjolin’s ulcer Burns 39:e25–28, 2013

Leukemia – leukemia cutis J Clin Neonatol 3:122–123, 2014; Cutis 21:814, 1978

Pigmented purpuric eruptions – including Gougerot-Blum pigmented purpuric eruption Cutis 31:406, 1983

Lymphangioendothelioma J Cutan Pathol 42:217–221, 2015

Post-inflammatory hyperpigmentation Ann Int Med 96693, 1982

Lymphoma – diffuse large B-cell lymphoma, leg type Pathol Oncol Res 18:1067–1069, 2012; Cutis 21:814, 1978;

Post-radiation pseudosclerodermatous panniculitis Int J Dermatol 158:e249–250, 2019

Melanoma – primary and metastatic Rom J Intern Med 52:121–123, 2014

Rosacea Arch Derm Syph 8:143, 1923 Sarcoid

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Kinky Hair 569

KINKY HAIR Ped Derm 21:265–268, 2004 Acquired progressive kinking of the hair Acquired woolly hair nevus Bjornstad syndrome Congenital pili torti syndrome Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of the face, knees, alopecia of the scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger- and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143–148, 1999

Rheumatoid arthritis – rheumatoid nodules; rheumatoid neutrophilic dermatitis – nodules over joints AD 133:757–760, 1997; AD 125:1105–1108, 1989; Bouchard’s nodes of rheumatoid arthritis Scleroderma – knuckle hyperkeratosis in systemic scleroderma Adult onset Still’s disease – erythema of eyelids, erythema of knuckles, red plaques of legs JAAD 79:969–971, 2018

DEGENERATIVE DISEASES Heberden’s nodes of knuckles – degenerative joint disease JAAD 43:892, 2000 DRUGS Acral dysesthesia syndrome Bleomycin-induced dermatomyositis-like rash JAAD 48:439–441, 2003 Ipilimumab – monoclonal antibody to cytotoxic T-lymphocyte antigen 4; dermatomyositis eruption with cuticular hypertrophy, photosensitive rash with knuckle papules JAMADerm 151:195–199, 2015

Isotretinoin Clin Exp Dermatol 15:143–145, 1990

Non-selective antiangiogenic multikinase inhibitors – sorafenib, sunitinib, pazopanib – hyperkeratotic hand-foot skin reactions with knuckle papules, inflammatory reactions, alopecia, kinking of hair, depigmentation of hair; chloracne-like eruptions, erythema multiforme, toxic epidermal necrolysis, drug hypersensitivity, red scrotum with erosions, yellow skin, eruptive nevi, pyoderma gangrenosum-like lesions JAAD 72:203–218, 2015

Menkes’ kinky hair syndrome – hair shaft abnormalities, most common pili torti Dermatol Online J Nov 15, 2012

Sorafenib – hyperkeratotic knuckle papules BJD 161:1045–1051, 2009

Pili annulati – kinky hair

Sunitinib – hyperkeratotic knuckle papules BJD 161:1045–1051, 2009

Etretinate Clin Exp Dermatol 10:426–431, 1985 Hereditary (familial) woolly hair syndrome Ionizing radiation BJD 113:467–473, 1985

Pseudomonilethrix Trauma – acquired localized trichorrhexis nodosa; hairspray J Saudi Soc Derm and Derm Surg 17:73–75, 2013 Trichonodosis – knotted hair Int J Trichol 6:31–33, 2014 Trichothiodystrophy – sulfur-deficient brittle hair Uncombable hair syndrome spun glass hair syndrome; mutations in PAD13, TGM3, TCHH Whisker hair – kinking of hair over periauricular areas of the scalp which evolves into extensive baldness

Tegafur – knuckle pad-like keratoderma Int J Dermatol 37:315–317, 1998 EXOGENOUS AGENTS Barber’s hair sinus Exogenous ochronosis Foreign body reactions

Woolly hair nevus – trichorrhexis nodosa-like Int J Trichology 10:180–182, 2018

INFECTIONS

Woolly head – personal observation

Gianotti-Crosti syndrome – personal observation Histoplasmosis J Cut Pathol 43:1155–1160, 2016

KNUCKLE PAPULES

Leishmaniasis – dermonodular leishmaniasis Clin Inf Dis 22:376– 377, 1996

(see also “Acral Papules and Nodules”)

Leprosy – primary neuritic leprosy with nerve abscess AD 130;243– 248, 1994; lepromatous – digital papule JAAD 11:713–723, 1984 Lobomycosis

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Dermatomyositis –Curr Opin Rheum 11:475–482, 1999; amyopathic; Gottron’s papules Joint Bone Spine 73:318–320, 2006; mechanics’ hands, anti-synthase syndrome Ann DV 146:19–25, 2019 Epidermolysis bullosa acquisita

Mycobacterium marinum – nodule or papule of the hands, elbows, and knees becomes crusted ulcer or abscess; or verrucous papule; sporotrichoid; rarely widespread lesions Br Med J 300:1069–1070, 1990; AD 122:698–703, 1986; J Hyg 94:135–149, 1985 Orf Acta DV Croat 27:280–281, 2019 Parvovirus B19 – dermatomyositis-like Gottron’s papules Hum Pathol 31:488–497, 2000

Lupus erythematosus with cutaneous mucinosis; discoid LE

Scabies – Norwegian scabies; hyperkeratotic knuckle papules Ped Derm 27:93–94, 2010

Mixed connective tissue disease

Verruca vulgaris – knuckle pads Derm Surg 27:591–593, 2001

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INFILTRATIVE DISEASES

PHOTODERMATOSES

Acral persistent papular mucinosis – mimicking knuckle pads Cutis 103:e3–5, 2019; AD 140:121–126, 2004; JAAD 27:1026–1029, 1992

Degenerative collagenous plaques of the hands

Focal mucinosis

PRIMARY CUTANEOUS DISEASES

Lichen myxedematosus – resembling acral persistent papular mucinosis BJD 144:594–596, 2001; Dermatology 185:81, 1992

Acanthosis nigricans

Mastocytoma knuckle pads Self-healing juvenile cutaneous mucinosis – knuckle nodules JAAD 50:S97–100, 2004; Ped Derm 20:35–39, 2003; JAAD 31:815–816, 1994;JAAD 11:327–332, 1984

INFLAMMATORY DISEASES

Acrokeratoelastoidosis of Costa – knuckle pads AD 140:479–484, 2004; Ped Derm 19:320–322, 2002; JAAD 22:468–476, 1990; Acta DV 60:149–153, 1980; Dermatologica 107:164–168, 1953 Acrokeratosis verruciformis of Hopf Collie-Davies palmoplantar keratoderma – personal observation Dermatitis papulosa juvenilis (sandbox dermatitis) Clin Exp Dermatol 34:620–622, 2009

Sarcoid – Darier-Roussy sarcoid JAMA Derm 149:22–228, 2013

Dupuytren’s disease – dorsal variant Ann Chir Main 7:247–250, 1988(Fr)

Stevens-Johnson syndrome – personal observation

Dyshidrosis with id reaction Epidermolysis bullosa, dominant dystrophic

METABOLIC DISEASES Acromegaly Calcinosis cutis Diabetic finger pebbling (Huntley’s papules) Int J Dermatol 44:755–756, 2005; Cutis 69:298–300, 2002 Gout – tophi Arch Orthop Trauma Surg 120:482–483, 2000 Porphyria – erythropoietic protoporphyria Thyroid acropachy Xanthomas – tuberous or tendinous xanthomas

Epidermolytic palmoplantar keratoderma (epidermolytic hyperkeratosis associated with palmoplantar keratoderma) – palmoplantar keratoderma and knuckle pads; KRT9 gene mutation Ped Derm 30:354–358, 2013; BJD 125:496, 1991 Erythema elevatum diutinum – violaceous knuckle pads, papules Cutis 101:462–465, 2018; BJD 164:675–677, 2011; JAAD 49:764– 767, 2003; Cutis 67:381–384, 2001; Ped Derm 15:411–412, 1998 Granuloma annulare JAAD 3:217–230, 1980; subcutaneous granuloma annulare mimicking knuckle pads; perforating granuloma annulare; papular umbilicated granuloma annulare Ped Derm 33:89–90, 2016 Hidrotic ectodermal dysplasia

NEOPLASTIC DISEASES Enchondromas Epidermoid cyst Fibroma of the tendon sheath Cutis 59:133, 1997 Ganglion cyst Giant cell tumor of the tendon sheath – nodules of the fingers Cutis 59:133, 1997; J Dermatol 23:290–292, 1996; overlying dorsal digital interphalangeal crease J Hand Surg 5:39–50, 1980 Infantile myofibromatosis JAAD 57:S30–32, 2007 Keloids Lymphoma – HTLV-1 leukemia/lymphoma – personal observation Melanocytic nevus Mobile encapsulated lipomas Cutis 49:63–64, 1992 Multinucleate cell angiohistiocytoma – red-brown-violaceous knuckle papules AD 147:975–980, 2011; BJD 113:15, 1985 Myxoid cyst, digital JAAD 43:892, 2000 Poroid hidradenoma Cutis 50:42–46, 1992 Progressive nodular fibrosis of the skin PARANEOPLASTIC DISORDERS Dermatomyositis Neutrophilic dermatosis of the dorsal hands Clin Dermatol 35:81– 84, 2017; J Hand Surg Am Feb 2015

Juvenile fibromatosis Knuckle pads – familial, autosomal dominant; idiopathic (fibromatosis), keratotic knuckle pads unassociated with palmoplantar keratoderma trauma-induced, associated with Dupuytren’s contracture, Ledderhose’s disease, Peyronie’s disease, BartPumphrey syndrome – mixed sensorineural and conductive deafness, leukonychia, and knuckle pads; autosomal dominant Ped Derm 17:450–452, 2000; Cutis 57:241–242, 1996; associated with palmoplantar keratoderma, acrokeratoelastoidosis of Costa, keratoderma hereditaria mutilans, pseudoxanthoma elasticum Lichen nitidus – knuckle pads Int J Dermatol 50:1334–1335, 2011; AD 134:1302–1303, 1998; hyperkeratotic and hypertrophic lichen nitidus Dermatol Online J Oct 15, 2017 Lichen planus Lichen simplex chronicus Necrolytic acral erythema – serpiginous, verrucous plaques of dorsal aspects of the hands and legs; associated with hepatitis C infection JAAD 50:S121–124, 2004 Neurofibromatosis Pachydermodactyly – digital fibromatosis; bilateral asymptomatic swelling of soft tissues surrounding the PIP joints of the second and fourth fingers; benign fibromatosis of the fingers of young men; thought to be trauma-related; large knuckles AD 148:925–928, 2012; AD 144:1651–1656, 2008; Clin Rheumatol 26:962–964, 2007; Clin Exp Dermatol 28:674–675,2003; Ann DV 125:247–250, 1998; BJD 133:433–437, 1995; AD 111:524, 1975; Bull Soc Fr Dermatol Syphiligr 80:455–458, 1973

Knuckle Papules 571 Palmoplantar keratoderma, epidermolytic (Vorner) – papules on knuckles BJD 125:496, 1991 Pityriasis rubra pilaris Progressive symmetric erythrokeratoderma Prurigo nodularis Pseudo-acanthosis nigricans – personal observation

around the nose, behind the ears, on the fingertips, hyperpigmented papules/plaques over the MCP joints and malleoli; multiple subcutaneous nodules of the scalp, trunk, and extremities, papillomatous perianal papules; joint contractures, skeletal lesions, gingival hyperplasia, stunted growth Indian J Dermatol 61:580, 2016;; AD 121:1062–1063, 1985; AD 107:574–579, 1973

Psoriasis

Keratosis-ichthyosis-deafness (KID) syndrome – partial leukonychia, deafness JAAD 53:S225–230, 2005

Unna-Thost palmoplantar keratoderma

Knuckle pads, leukonychia, and deafness syndrome

Vorner’s palmoplantar keratoderma

Knuckle pads with palmoplantar keratoderma and acrokeratoelastoidosis

PSYCHOCUTANEOUS DISEASES Bulimia nervosa – Russell’s sign (crusted knuckle nodules) JAAD 76:779–791, 2017; Clin Orthop 343:107–109, 1997; JAAD 12:725– 726, 1985; perniosis Clin Sci 61:559–567, 1981; pseudo knuckle pads (calluses on second and fifth MCP joints) Psychol Med 9;429–48, 1979 Pachydermodactyly due to obsessive compulsive behavior JAAD 38:359–362, 1998; AD 130:387, 1994

SYNDROMES Bart-Pumphrey syndrome – knuckle pads, leukonychia, sensorineural deafness, and diffuse palmoplantar hyperkeratosis; autosomal dominant JAAD 53:S225–230, 2005; Clin in Dermatol 23:23–32, 2005; JAAD 51:292, 2004; Curr Prob Derm 14:71–116, 2002; J Med Genet 31:68–71, 1994; NEJM 276:202–207, 1967 Dyskeratosis congenita

Ledderhose’s nodules (plantar fibromatosis) JAAD 41:106–108, 1999; Dupuytren’s contracture (palmar fibromatosis) and/or Peyronie’s disease – knuckle pads Lipoid proteinosis – acral papules BJD 151:413–423, 2004; JID 120:345–350, 2003; BJD 148:180–182, 2003; Hum Molec Genet 11:833–840, 2002 Mal de Meleda (recessive transgressive palmoplantar keratoderma) – knuckle pads Indian J Dermatol 57:390–393, 2012; Curr Prob Derm 14:71–116, 2002; Ped Derm 14:186–191, 1997 Multicentric reticulohistiocytosis – digital papule; knuckle pads; yellow papules and plaques Clin Rheumatol 35:527–534, 2016; AD 140:919–921, 2004; AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968 Neurofibromatosis Pachydermoperiostosis – knuckle pads J Dermatol 27:106–109, 2000 Pachyonychia congenita

Familial histiocytic dermatoarthritis – knuckle pads

Palmoplantar keratoderma, pseudoainhum (constriction bands), knuckle pads, hearing loss – mutation in GJB6 encoding connexin 30 BJD 161:452–455, 2009

Farber’s disease (disseminated lipogranulomatosis) – red papules and nodules of joints and tendons of the hands and feet; deforming arthritis; papules, plaques, and nodules of the ears, back of the scalp, and trunk Am J Dis Child 84:449–500, 1952

Papillon-Lefevre syndrome – keratotic papules over the knuckles (metacarpophalangeal and proximal interphalangeal joints); palmoplantar keratoderma, pitted on the heels and forefoot; cathepsin C mutation Ped Derm 30:749–750, 2013

Fibroblastic rheumatism – symmetrical polyarthritis, nodules over the joints and on the palms, elbows, knees, ears, and neck, Raynaud’s phenomenon, sclerodactyly; skin lesions resolve spontaneously AD 139:657–662, 2003; Ped Derm 19:532–535, 2002; AD 131:710–712, 1995; Clin Exp Dermatol 19:268–270, 1994; JAAD 14:1086–1088, 1986; Rev Rheum Ed Fr 47:345–351, 1980

Polyfibromatosis syndrome – Dupuytren’s contracture, knuckle pads, Peyronie’s disease, keloids, or plantar fibromatosis stimulation by phenytoin BJD 100:335–341, 1979

Ehlers-Danlos syndrome (molluscum pseudotumor) – knuckle pads

Francois syndrome (dermochondrocorneal dystrophy) – knuckle pads; nodules on the hands, nose, and ears Ann DV 104:475–478, 1977; AD 124:424–428, 1988

PTEN hamartoma tumor syndrome – mucocutaneous neuromas AD 142:625–632, 2006 Reflex sympathetic dystrophy with chilblain-like lesions – digital papule Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – perniotic lesions JAAD 21:374–377, 1989

Greither’s palmoplantar keratoderma – knuckle pads, hyperkeratosis of the elbows, knees, and shins JAAD 53:S225–230, 2005

Stiff skin syndrome – knuckle pads JAAD 75:163–168, 2016;

Hunter syndrome – MPS II Ped Derm 12:370–372, 1995

Vohwinkel’s syndrome (keratoderma hereditaria mutilans) – autosomal dominant; honeycomb palmoplantar keratoderma, hyperkeratotic knuckle papules with starfish keratoses; ichthyosis, pseudoainhum; JAAD 44:376–378, 2001; with congenital sensorineural deafness – mutation in GJB2 (connexin 26) (gap junction protein), D66H; or loricrin mutations BJD 164:197–199, 2011; Clinics in Dermatol 23:23–32, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 44:376–378, 2001; BJD 145:657–660, 2001; Hum Mol Genet 8:1237–1243, 1999; loricrin mutation JID 111:702–704, 1998; Nat Genet 13:70–77, 1996

Infantile digital fibromatosis Infantile systemic hyalinosis – autosomal recessive; synophrys, thickened skin, perianal nodules, dusky red plaques of the buttocks, gingival hypertrophy, joint contractures, juxta-articular nodules (knuckle pads), osteopenia, growth failure, diarrhea, frequent infections, facial red papules JAAD 50:S61–64, 2004; Ped Derm 11:52–60, 1994 Juvenile hyaline fibromatosis – rare, autosomal recessive; pearly white papules of the face and neck; larger papules and nodules

Ped Derm 3:48–53, 1985

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TRAUMA

INFILTRATIVE

Biter’s nodule

Lichen myxedematosus

Callosities, occupational (carpenters, live chicken hangers Contact Derm 17:13–16, 1987), frictional, bulimic

Persistent acral mucinosis

Chilblains (perniosis) – tender, pruritic red or purple digital papules Int J Dermatol 52:1295–1296, 2013; JAAD 45:924–929, 2001; AD 132:459–462, 1996; Frictional callosities Knuckle pad (Garrod’s pads, heloderma, subcutaneous fibroma, keratosis supracapitularis, discrete keratoderma) – violinist’s knuckles (second and third knuckles) – thickened skin over the interphalangeal joints from intense flexion of the tendons of the fingers Cutis 62:261–262, 1998; St Bartholomew’s Hosp Rep 29:157–161, 1893; knuckle pads due to video game Ped Derm 23:455–457, 2006; occupational callosities – personal observation Scars – mimic knuckle pads Secondary knuckle pads due to chewing, bulimia; occupational – plumbers, carpet layers, mechanics, tailors, textile workers, plasterers, live chicken hangers; sports – football, surfers, boxers AD 143:1458–1460, 2007 Skier’s thumb Acta Orthop Belg 65:440–446, 1999

METABOLIC Diabetic finger pebbling (Huntley’s papules) Cutis 69:298–300, 2002 Erythropoietic protoporphyria BJD 155:574–581, 2006 Intertriginous xanthomas in fingerweb spaces of homozygous familial hypercholesterolemia JAAD 19:95–111, 1988 Porphyria cutanea tarda

NEOPLASTIC Infantile digital fibromatosis Solitary mastocytomas – Scotch grain leather appearance Photodermatosis Dermatoheliosis (chronic sun damage)

Sports-related knuckle pads Int J Dermatol 4:291–293, 2002 Surfer’s nodules of anterior tibial prominence, dorsum of the feet, knuckles Cutis 50:131–135, 1992

PRIMARY CUTANEOUS DISEASE

VASCULAR LESIONS

Acral localized acquired cutis laxa (wrinkled knuckles) JAAD 21:33–40, 1989

Glomus tumors Lymphedema praecox Vascular hamartomas Vasculitis

Acanthosis nigricans

Acrokeratosis verruciformis of Hopf Epidermolysis bullosa – resolving dystrophic epidermolysis bullosa Erythema elevatum diutinum Granuloma annulare Knuckle pads Cutis 57:241–242, 1996

KNUCKLES, PEBBLY, WITH SCARRING

Lichen nitidus

“Why do my hands look so old?”

Pachydermodactyly

Lichen simplex chronicus Pseudo-acanthosis nigricans

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Pseudo-PCT

Dermatomyositis – Gottron’s papules

SYNDROMES

Rheumatoid arthritis – velvet skin

Dyskeratosis congenita

Scleroderma

Lipoid proteinosis Multicentric reticulohistiocytosis

EXOGENOUS AGENTS Foreign body granuloma

INFECTIONS Acrodermatitis chronica atrophicans (peripheral atrophy) JAAD 28:399–405, 1993 Leprosy Verruca vulgaris

Neurofibromatosis

TRAUMATIC Bulimia (Russell’s sign) Postgrad Med J 70:27–30, 1994 Garrod’s pads (violinist’s knuckles) – thickened skin over the interphalangeal joints from intense flexion of the tendons of the fingers Occupational callosities – carpenters, live chicken hangers; hardwood floor installer Contact Derm 17:13–16, 1987

LACRIMAL GLAND, ENLARGED

breasts and nipples, urinary tract anomalies; mutation in TP63 gene (encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes BJD 172:276–278, 2015; Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993

UNILATERAL Amyloidosis Radiol Clin North Am 37:219–239, 1999 Benign tumors  Myoepithelioma Ophthalmol Clin North Am 13:663–681, 2000   Pleomorphic adenoma Radiol Clin North Am 37:219–239, 1999

LENTIGINES

Malignant tumors Ophthalmol Clin North Am 13:663–681, 2000   Adenocystic carcinoma  Lymphoma Radiol Clin North Am 37:219–239, 1999  Leukemia Radiol Clin North Am 37:219–239, 1999    Acute lymphoblastic leukemia   Granulocytic leukemia   Mucoepidermoid carcinoma   Pleomorphic adenocarcinoma   Primary adenocarcinoma

JAAD 50:690–694,2004

DRUGS Apremilast – lentigines at sites of psoriasis treated with apremilast Clin Exp Dermatol 44:66–67; JAAD 75:1251–1252, 2016; after ustekinumab Ann Dermatol 30:371–372, 2018 Doxorubicin/daunorubicin – melanotic macules JAAD 71:203–214, 2014

Chronic inflammation Dacryoadenitis  Bacterial Ann Ophthalmol 14:600, 1982  Fungal Ann Ophthalmol 14:600, 1982  Parasitic J Pediatr Ophthalmol 19:100, 1982  Viral   Herpes simplex Arch Ophthalmol 56:739, 1961   Mumps Arch Ophthalmol 56:739, 1961

Imatinib – loss of lentigines AD 145:1313–1316, 2009 Pimecrolimus – acquired (inducible) lentiginosis AD 148:766–768, 2012; BJD 152:152–154, 2005 Tacrolimus – acquired (inducible) lentiginosis AD 148:766–768, 2012; Ped Derm 27;562–563, 2010; BJD 152:152–154, 2005 Voriconazole – in immunosuppressed patients; chronic phototoxicity with aggressive squamous cell carcinomas; sunburn-like erythema, multiple lentigines, multiple actinic keratoses, cheilitis, exfoliative dermatitis, pseudo-porphyria cutanea tarda, telangiectasias AD 146:300–304, 2010; JAAD 62:31–37, 2010; acral photo-distributed lentigines JAMADerm 150:334–335, 2014

Dermoid cyst Radiol Clin North Am 25:767, 1987 Idiopathic inflammatory pseudotumor Ophthalmol 103:1233, 1996 Kimura’s disease Ophthalmol 100: 1856–1860, 2000 Lymphoid hyperplasia, benign Radiol Clin North Am 37:219–239, 1999 Sarcoidosis Ophthalmol 90:909, 1983

EXOGENOUS AGENTS BILATERAL

Radon exposure Dermatology 221:206–210, 2010

Chronic renal failure

Squaric acid dibutyl ester AD 139:544–555, 2003

IgG4 disease – multisystem inflammatory disease with papules, plaques, and nodules; parotitis with parotid gland swelling, lacrimal gland swelling, dacryoadenitis, sialadenitis, proptosis; idiopathic pancreatitis, retroperitoneal fibrosis, aortitis; Mikulicz’s syndrome, angiolymphadenopathy with eosinophilia, Riedel’s thyroiditis, biliary tract disease, renal disease, meningeal disease, pituitary gland; Kuttner tumor, Rosai-­Dorfman disease; elevated IgG4 with plasma cell dyscrasia, diffuse or localized swelling or masses; lymphocytic and plasma cell infiltrates with storiform fibrosis NEJM 376:775– 786, 2017; JAAD 75:197–202, 2016; JAAD 75:177–185, 2016

INFECTIONS AND INFESTATIONS Chikungunya fever – freckles of face and ears, acral, confetti macules Indian J Dermatol 54:128–131, 2009

METABOLIC DISEASES Addison’s disease – increase in number and darkening; lentigines of palms, soles, and vulva JAAD 58:522–524, 2008; masquerading as Laugier-Hunziker syndrome Int J Dermatol 47:596–598, 2008

Lymphoid hyperplasia, benign Radiol Clin North Am 37:219–239, 1999

Cushing’s syndrome – increase in number and darkening

Lymphoma Radiol Clin North Am 37:219–239, 1999

Diabetic post-inflammatory hyperpigmentation – lentigo-like macules BJD 171:1402–1406, 2014

Sarcoidosis Ophthalmol 90:909, 1983 Sjogren’s syndrome Radiol Clin North Am 37:151–168, 1999

Pregnancy – increase in number and darkening

Polyangiitis with granulomatosis Br J Ophthalmol 76:401, 1992

NEOPLASTIC DISEASES

LACRIMAL DUCT ATRESIA Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, superficial blisters and desquamation of hands and feet; lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears, hooked nose, sparse thin blond hair, frontal alopecia, hypohidrosis, lacrimal duct atresia, hypoplastic

Achromic nevi – lentigines within segmental achromic nevi Clin Exp Dermatol 33:337–339, 2008; JAAD 39:330–333, 1998 Agminated lentiginosis Ped Derm 11:241–245, 1994; café au lait macules, mental retardation, epilepsy, pes cavus JAAD 40:877–890, 1999 Agminated Spitz nevi – inguinal freckling Ped Derm 27:282–284, 2010

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Benign acquired lentiginosis – with polycythemia vera; JAK-2 mutation JAKSTAT 24:e1071000, 2015; with hepatocellular cancer SKINMed 12:64–65, 2014; with melanoma J Eur Acad DV 22:1262– 1263, 2008 Benign labial lentigo BJD 136:772–775, 1997; AD 123:1029–1031, 1987 Eruptive lentiginosis – young adults, generalized distribution; eruptive lentigines subsequently evolving into melanocytic nevi BJD 72:302–311, 1960; Ann Dermatol Syphilol 83:125–129, 1956 Familial gastrointestinal stromal tumor (GIST) with kit mutation Clin Exp Dermatol 44:418–421, 2109 Ink spot lentigo (reticulated black solar lentigo) Clin Derm 37:447– 467, 2019; AD 128:934–940, 1992 Melanoma – lentiginous lesions of vulva or penis AD 147:1181– 1187, 2011 Nevus depigmentosus with lentiginosis – hypopigmentation and lentigines JAAD 54:S238–240, 2006 Nevus spilus JAAD 61:337–341, 2009 Penile lentigo JAAD 76:836–840, 2017; JAAD 22:453–460, 1990 Seborrheic keratosis mimicking ink spot lentigo – personal observation Spitz nevi arising in nevus spilus JAMA Derm 149:1077–1080, 2013 Vulvar lentigo JAAD 76:836–840, 2017; Dermatol Clin 10:361–370, 1992; JAAD 22:453–460, 1990

Harlequin ichthyosis – increased numbers of nevi and lentigines Ped Derm 37:192–195, 2020 Oral and pedal lentiginosis (disseminated plantar lentigines associated with Peutz-Jeghers syndrome) Rev Gastr Mex 8:168– 169, 2016 Psoriasis – lentigines confined to resolving psoriatic plaque JAAD Case Rep 10:924–929, 2018; Clin Exp Dermatol 19:380–382, 1994 Segmental lentiginosis (partial unilateral lentiginosis) (unilateral lentiginosis) JAAD 44:387–390, 2001; Clin Exp Dermatol 20:141– 142, 1995; JAAD 29:693–695, 1993

SYNDROMES ADULT (acro-dermato-ungual lacrimal tooth syndrome) – limb mammary syndrome-like syndrome with ectrodactyly, mammary hypoplasia, excess freckling without facial freckling Hum Mol Genet 11:799–804, 2002 ANOTHER syndrome – alopecia, nail dystrophy, ophthalmic complications, thyroid dysfunction, hypohidrosis, ephelides and enteropathy, respiratory tract infections Clin Genet 35:237–242, 1989; J Pediatr 108:109–111, 1986 Bandler syndrome – autosomal dominant, Peutz-Jeghers-like lentigines; gastrointestinal bleeding with vascular malformations of the small intestine JAAD 62:171–173, 2010

Tanning bed lentigines JAAD 23:1029–1031, 1990; JAAD 21:689– 693, 1989

Bannayan-Riley-Ruvalcaba syndrome (macrocephaly and subcutaneous hamartomas) (lipomas and hemangiomas) – autosomal dominant pigmented macules of the penis JAAD 68:189–209, 2013; JAAD 56:541–564, 2007; JAAD 53:639–643, 2005; AD 132:1214– 1218, 1996; AD 128:1378–1386, 1992; Eur J Ped 148:122–125, 1988; lipoangiomas (perigenital pigmented macules, macrocephaly) AD 128:1378–1386, 1992; lipomas in Ruvalcaba-Myhre-Smith syndrome Ped Derm 5:28–32, 1988; Ruvalcaba-Myhre-Smith syndrome – pigmented penile macules, lipomas, angiolipomas, macrocephaly, pseudopapilledema, hamartomas, lipid-storage myopathy AD 132:1214–1218, 1996; Curr Prob in Derm VII:143– 198, 1995; Pediatrics, 81:287–290, 1988

PRIMARY CUTANEOUS DISEASES

Cantu syndrome – autosomal dominant, lentigines on palms and soles and sun-exposed skin, palmoplantar hyperkeratotic papules Curr Prob in Derm VII:143–198, 1995

Zosteriform lentiginous nevus

PHOTODERMATOSES PUVA-induced Clin Exp Dermatol 25:135–137, 2000; Cutis 41:199–202, 1988; JID 81:459–463, 1983 Solar lentigines JAAD 36:444–447, 1997

Agminated lentiginosis with multiple café au lait macules Clin Exp Dermatol 32:658–660, 2007 Atopic dermatitis – lentigines at sites of healed atopic dermatitis Ped Derm 36:970–972, 2019 Atrophoderma of Moulin – acquired atrophic pigmented band-like lesions following Blaschko’s lines with lentigines BJD 163:1138– 1140, 2010 Epidermolysis bullosa – generalized atrophic benign EB (GABEB) (mitis) – non-lethal junctional, generalized blistering beginning in infancy; nevi or acquired macular pigmented lesions with irregular borders AD 122:704–710, 1986 Eruptive lentiginosis Bull Soc Fr Derm Syph 40:1049–1051, 1930; La Pratique Dermatologique Vol III Paris:Masson; 1902, p.466 Galli-Galli disease – lentigines and papules Acta DV Croat 25:300–302, 2017; AD 148:641–646, 2012 Generalized lentiginosis Ped Derm 21:139–145, 2004; Eur J Dermatol 18:183–185, 1998; JAAD 18:444–447, 1988; acquired sporadic generalized lentiginosis Eur J Dermatol 8:183–185, 1998 Genital lentiginosis in the presence of lichen sclerosus JAAD 50:690–694,2004

Carney complex (NAME/LAMB syndrome) – autosomal dominant; pink papules of face (myxomas); multiple lentigines of upper lips, genitalia, conjunctivae, inner and outer canthi, palms, vulva, penis, melanocytic nevi, small blue nevi, cutaneous myxomas (red papules or pedunculated papules), psammomatous schwannoma, cardiac myxomas, testicular Sertoli cell tumors, gynecomastia, myxoid breast fibroadenomas, pituitary adenomas, acromegaly, testicular calcification, thyroid carcinoma, breast ductal carcinoma, osteochondromyxoma, thyroid disease, Cushing’s syndrome due to primary pigmented nodular adrenocortical disease; growth hormone-producing pituitary adenomas; large-cell calcifying Sertoli cell tumor of the testis; PRKAR1A (protein kinase A type-1 regulatory subunit of cAMP dependent protein kinase A); lentigines fade with time Ped Derm 36:160–162, 2019; JAAD 61:80–87, 2009; JAAD 59:801–810, 2008; Clin in Dermatol 23:56–67, 2005; JAAD 46:161–183, 2002; Molec Genet Metab 78:83, 2003; J Clin Endocrinol 86:4041, 2001; Curr Prob in Derm VII:143–198, 1995; Medicine (Baltimore) 64:270–283, 1985; Br Heart J 35:874–876, 1973; conjunctival lentigines JAAD 42:145, 2000; epithelioid blue nevus and psammomatous melanotic schwannoma Semin Diagn Pathol 15:216–224, 1998; J Clin Invest 97:699–705, 1996; Dermatol Clin 13:19–25, 1995; JAAD 10:72–82, 1984; acromegaly, facial lentigines, cutaneous myxoma, blue nevus of vulva; gain of function

Lentigines mutation of PRKACB (catalytic subunit alpha of cAMP-dependent protein kinase NEJM 370:1065–1067, 2014 Centrofacial lentiginosis – synophrys, high-arched palate, sacral hypertrichosis, spina bifida, scoliosis BJD 94:39–43, 1976 Centrofacial neurodysraphic lentiginosis BJD 94:39–43, 1976 Congenital diffuse mottling of the skin – mottled pigmentation, café au lait macules, facial lentigines Ped Derm 24:566–570, 2007 Constitutional mismatch repair-deficiency (CMMR-D) syndrome – lentigines and café au lait macules; childhood and adulthood development of leukemias, lymphomas, brain tumors, colonic polyposis with cancer NEJM 370:2229–2236, 2014 Cowden’s disease – periorificial and acral pigmented macules; genital lentigines – personal observation; Dermatol Online J May 2019; J Natl Cancer Inst 105:1607–1616, 2013; Head Neck Pathol 10:131–138, 2006 Cronkhite-Canada syndrome – lentigo-like macules of face, extremities, and diffuse pigmentation of palms; gastrointestinal polyposis, malabsorption, alopecia, dystrophic nails AD 135:212, 1999 Ear deformity with genital and ear lentiginosis – personal observation FACES syndrome(unique facies, anorexia, cachexia, eye, skin lesions) – speckled lentiginous nevus J Craniofac Genet Dev Biol 4:227–231, 1984

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Lentiginosis with cutaneous myxomas JAAD 44:282–284, 2001 Lentiginosis with osteochondromyxoma of bone Am J Surg Pathol 25:164–1776, 2001 Lentiginosis with nevoid hypopigmentation BJD 144:188–189, 2001 Lentiginosis perigenito-axillaris – genital and acral pigmented macules Z Haut Geschlechtskr 42:19–22, 1967 Lentiginosis with testicular microlithiasis Clin Exp Dermatol 25:655–656, 2000 LEOPARD syndrome (multiple lentigines syndrome; Moynahan syndrome) – autosomal dominant; generalized lentiginosis, especially over neck and trunk; structural cardiac abnormalities, cardiac symptoms, electrocardiographic abnormalities, genitourinary abnormalities (gonadal hypoplasia, hypospadius, delayed puberty), neurologic defects, cephalofacial dysmorphism, short stature or low birth weight, skeletal abnormalities; deafness; mutation in PTPN11(RAS-mitogen-activated protein kinase 1(MAP) kinase pathway BJD 161:1202–1204, 2009; Clin in Dermatol 23:56–67, 2005; Ped Derm 21:139–145, 2004; JAAD 46:161–183, 2002; J Med Genet 34:582–586, 1997; Am J Dis Child 117:652– 662, 1969; café noir spots Ped Derm 25:444–448, 2008; with multiple granular cell tumors AD 146:337–342, 2010 McCune-Albright syndrome – lentigines of lips; GNAS mutation JAMADerm 150:760–763, 2014; Br J Oral Surg 6:188–191, 1969; JAMA 205:618–626, 1968

Familial generalized lentiginosis Int J Derm 35:357–359, 1996

Moynahan syndrome – profuse lentigines, congenital mitral stenosis, dwarfism, mental retardation, genital hypoplasia Orv Hetil 130:1531–1532, 1989

Familial hyper- and hypopigmentation – hypopigmentation, hyperpigmentation, lentigines, café au lait macules; mutation in KITLG (kit ligand) BJD 175:1369–1371, 2016

Mucocutaneous pigmentation with intestinal hemangiomatosis – Peutz-­Jeghers-­like lentiginosis with intestinal hemangiomatosis Gastroenterology 38:641–645, 1960

Fanconi’s anemia – freckle-like hyperpigmentation in sun-exposed areas, abdomen, flexures, and genitals Dermatol Clin 13:41–49, 1995

Mukamel syndrome – autosomal recessive; premature graying in infancy, lentigines, depigmented macules, mental retardation, spastic paraparesis, microcephaly, scoliosis Am J Dis Child 139:1090–1092, 1985

Familial eruptive lentiginosis JAAD 55:S38–40, 2006

Gardner’s syndrome – lentigines of head and extremities JAAD 45:940–942, 2001 Gastro-cutaneous syndrome – peptic ulcer/hiatal hernia, multiple lentigines, café au lait macules, hypertelorism, myopia Am J Med Genet 11:161–176, 1982 Gaucher’s disease – diffuse hyperpigmentation, easy tanning, pigmented macules BJD 111:331–334, 1984 Goltz’s syndrome – lentigines within Indian J Dermatol 62:498–504, 2017; Ped Derm 20:249–253, 2003 Halal syndrome – autosomal dominant; multiple lentigines, café au lait macules, hypertelorism, myopia, hiatal hernia/peptic ulcer Am J Med Genet 11:161–176, 1982 Harlequin ichthyosis and lentigines Ped Derm 37:192–195, 2000 Hermansky-Pudlak syndrome – multiple lentigines and ephelides – personal observation Inherited patterned lentiginosis in blacks – lentigines on face and lips, buttocks and extremities AD 125:1231–1235, 1989 Laugier-Hunziker syndrome – macular pigmentation of lips, gingival, tongue and buccal mucosa, palms and soles; linear melanonychia, genital macules AD 143:631–633, 2007; JAAD 50:S70–74, 2004; J Eur Acad Dermatol Venereol 15:574–577, 2001; Hautarzt 42:512– 515, 1991; Clin Exp Derm 15:111–114, 1990; Arch Belges Dermatol Syph 26:391–399, 1970 Legius syndrome – SPRED1 mutations Ped Derm 30:379–382, 2013 Lentiginosis with arterial dissection syndrome NEJM 332:576–579, 1995

Multiple mucosal neuroma syndrome (MEN IIB) – perioral or periocular lentigines, freckles, or hyperpigmentation Neurofibromatosis type I-like (NF-1-like) syndrome – autosomal dominant; multiple café au lait macules, axillary freckling, macrocephaly; Noonan-like dysmorphic changes; mutation in SPRED-1 gene; SJPRED-1 protein negatively regulates Ras-mitogenactivated protein kinase (MAPK) Noonan’s syndrome with multiple lentigines; PTPN mutation Pediatr Endocrinol Rev 16(suppl 2)428_434, 2019; BJD 180:1438–1448, 2019 Novel KIT mutation – marked lentiginosis of mons pubis and gluteal cleft Ped Derm 36:922–925, 2019 Progressive hyperpigmentation and lentigines – mutation in K17 BJD 179:1210–1211, 2018 Segmental neurofibromatosis – with lentiginosis J Dermatol 44:29–35, 2017; Arch Pediatr 20:89–90, 2013; J Dermatol 22:958– 959, 1995 Noonan-like syndrome, cherubism and polyarticular villonodular synovitis Oral Surg Oral Med Oral Pathol 67:698–705, 1989 Partial unilateral lentiginosis – multiple lentigines and café au lait macules in segmental distribution J DV Leprol 85:130, 2019; associated with segmental neurofibromatosis J Dermatol 22:958– 959, 1995 Peutz-Jeghers syndrome – autosomal dominant; oral lentigines of gums, buccal mucosa, hard palate, lips, around nose and mouth, palms and soles, dorsal hands and feet; lentigines fade with time

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except mucosal lesions; gastrointestinal polyposis, clubbing, ovarian tumors, precocious puberty with hormone-secreting tumors; mutation in STK11 NEJM 380:472, 2019; JAAD 68:189–209, 2013; Clin in Dermatol 23:56–67, 2005; Curr Prob Derm 14:41–70, 2002; Cancer Res 58:5267–5270, 1998; Curr Prob in Derm VII:143–198, 1995; Gut 30:1588–1590, 1989; NEJM 316:1511–1514, 1987; Gastroenterology 32:434–451, 1957; NEJM 241:992–1005, 1949; Nederl Maandisch v Geneesk 10:134–146, 1921; Arch Surg (Lond)7:290, 1896; Lancet 2:1169, 1895

Pigmented actinic keratosis

Phakomatosis pigmentokeratotica – coexistence of an organoid nevus and a checkerboard papular speckled lentiginous nevus; organoid nevus associated with hypophosphatemic vitamin D-resistant rickets; central and peripheral nervous system, ocular, vascular involvement, extracutaneous tumors, ptosis SkinMed 11:125–128, 2013; JAAD 55:S16–20, 2006; Eur J Dermatol 10:190–194, 2000; Ped Derm 15:321–323, 1998; AD 134:333–337, 1998; Dermatology 197:377–380, 1998

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Piebaldism, multiple café au lait macules, and intertriginous freckling; penile lentigines – KIT and SPRED1 mutations Ped Derm 30:379–382, 2013 Pipkin’s syndrome – autosomal dominant, nystagmus, strabismus Progeria – axillary freckling

Seborrheic keratoses, macular Solar lentigines Turner's syndrome

LEONINE FACIES

Allergic contact dermatitis Dermatomyositis

DRUG REACTIONS Bactrim drug eruption Minoxidil – pseudoacromegaly JAAD 48:962–965, 2003 Phenytoin hypersensitivity syndrome – coarse facial features, enlarged lips and nose JAAD 18:721–741, 1988

Progressive cardiomyopathic lentiginosis Ped Derm 1:146–153, 1953 Speckled lentiginous nevus syndrome – speckled lentiginous nevus with ipsilateral sensory and motor neuropathy, hyperhidrosis, spinal muscle atrophy with fasciculations, dysesthesias, muscle weakness, muscle atrophy, nerve palsy Ped Derm 26:298–301, 2009; Eur J Dermatol 12:133–135, 2002; ipsilateral shortening of limb and vertebral malformations Acta DV (Stockh)74:327–334, 1994 Tay’s syndrome – autosomal recessive Touraine centrofacial lentiginosis – autosomal dominant, lentigines in butterfly distribution and forehead, central nervous system abnormalities, high forehead, high-arched palate, pectus deformities, kyphosis, spina bifida, umbilical hernias BJD 94:39–43, 1976 Watson’s syndrome – café au lait macules, axillary and perianal freckling, pulmonic stenosis, low intelligence, short stature JAAD 46:161–183, 2002; JAAD 40:877–890, 1999 Werner’s syndrome with incomplete LEOPARD syndrome Clin Exp Dermatol 20:46–59, 1995 Xeroderma pigmentosum JAAD 75:855–870, 2016; BJD 172:1096– 1102, 2015; BJD 169:1279–1287, 2013; AD 145:910–915, 2009; JAAD 59:881–886, 2008; BJD 152:545–551, 2005; AD 123:241–250, 1987

EXOGENOUS AGENTS Airborne ragweed contact dermatitis

INFECTIONS Dermatophyte infection – generalized deep dermatophytosis (trichophytic granuloma) – Trichophyton rubrum AD 140:624–625, 2004 Coccidioidomycosis JAAD 55:929–942, 2006 Histoplasmosis SAGE Open Med Case Rep March 1, 2019.7:2050313X19829616 Leishmaniasis – diffuse cutaneous leishmaniasis (L. aethiopica, L. mexicana) JAAD 73:897–908, 2015;JAAD 60:897–925, 2009; JAAD 34:257, 1996; lupoid leishmaniasis Leprosy – lepromatous leprosy Clin Oral Invest Aug 21, 2019. doi.10.1007/S007840–190–3061–; An Bras Dermatol 92:389–391, 2017 Molluscum contagiosum, giant AD 147:652–654, 2011; Clin Inf Dis 52:1029–1030,1077–1078, 2011 Mycobacterium tuberculosis – lupus vulgaris

TRAUMA

Onchocerciasis – “mal marado”

Radiation lentigo AD 133:209–211, 1997

Syphilis – nodular secondary syphilis AD 144:1078–1079, 2008; JAAD 17:914, 1987; malignant secondary syphilis Int J STD-AIDS 22:298–300, 2011

VASCULAR DISEASES

Trichodysplasia spinulosa – polyoma virus infection of immunocompromised host; progressive alopecia of eyebrows initially, then scalp and body hair and red follicular papules of nose, ears, forehead; leonine facies Transpl Infect Dis 21(4):e13133.doi:10.1111/tid.13133 Aug 2019; JAMADerm 154:1342–1343, 2018; BJD 174:490–498, 2016; AD 146:871–874, 2010; JID Symposium Proceedings 4:268–271, 1999; DNA polyoma virus in renal transplant patient; alopecia, particulate matter, follicular papules, thickened skin, eyebrow alopecia, leonine facies JAAD 75:1–16, 2016; AD 148:726–733, 2012; AD 146:871–874, 2010; JAAD 60:169–172, 2009; J Cutan Pathol 34:721–725, 2007; AD 142:1643–1648, 2006; JAAD 50:310–315, 2004; J Invest Dermatol Symp Proc 4:268–271, 1999; Hautarzt 46:871–874, 1995

Arterial dissection

SPOTTY PIGMENTATION OF FACE Carney complex Cronkhite-Canada syndrome LEOPARD syndrome Noonan's syndrome with lentigines Peutz-Jeghers syndrome

Leonine Facies

INFILTRATIVE DISEASES Alopecia mucinosa Ped Derm 16:326–328, 1999 Amyloidosis JAAD 39:149–171, 1998; Singapore Med J 1193, 1970 Indeterminate cell histiocytosis Acta DV 98:463–464, 2018 Juvenile hyaline fibromatosis (infantile systemic hyalinosis) Ped Derm 23:458–464, 2006 Langerhans cell histiocytosis – primary cutaneous AD 127:1545– 1548, 1991 Mastocytosis Indian J Pathol Microbiol 55:566–568, 2012; South Med J 104:236–238, 2011 Progressive nodular histiocytosis JAAD 57:1031–1045, 2007; BJD 143:628–631, 2000; JAAD 29:278–280, 1993; JAAD 13:383–404, 1985; Int J Dermatol 12:248–260, 1974; progressive nodular histiocytoma Lancet 24:208–209, 1987 Scleredema diabeticorum Dermatol Online J 19(12):20718, Dec 16, 2013 Scleromyxedema (lichen myxedematosus) – linear papules, leonine facies, arthritis and rash, sclerodermoid changes Arthr Rheumatol 70:1694, 2018.doi:10.1002/art.40530; J Drugs in Dermatol 13:619–620, 2014; JAAD 69:1062–1066, 2013; JAAD 69:66–72, 2013; BJD 144:594–596, 2001; JAAD 44:273–281, 2001; JAAD 289–294, 1998; AD 123:786–789, 1987 Sea blue histiocytosis – facial macular brown hyperpigmentation; nodules of face, trunk, hands, and feet; eyelid infiltration; puffy face; leonine facies JAAD 57:1031–1045, 2007 Xanthoma disseminatum JAAD 13:383, 1985; AD 121:1313–1317, 1985

INFLAMMATORY DISEASES Lymphocytoma cutis AD 130:155–156, 1994 Rosai-Dorfman disease Eur J Dermatol 28:255–256, 2018 Sarcoid Clin Exp Dermatol 34:639–640, 2009; Cutis 73:57–62, 2004; AD 136:712–714, 2000; AD 133:215–219, 1997; JAAD 24:451, 1991; Ann DV 116:816–817, 1989

METABOLIC Acromegaly Cretinism – coarse facial features, lethargy, macroglossia, cold dry skin, livedo, umbilical hernia, poor muscle tone, coarse scalp hair, synophrys, no pubic or axillary hair at puberty

Keratoacanthomas, multiple; generalized eruptive keratoacanthomas of Grzybowski – masked facies BJD 142:800–803, 2000 Leukemia cutis – chronic lymphocytic leukemia (B-cell) Leukemia & Lymphoma 49:1217–1219, 2008; congenital monocytic leukemia BJD 150:753–756, 2004; congenital leukemia, chronic myelogenous leukemia with blast transformation JAAD 12:943–8, 1985; JAAD 11:121–8, 1984; chronic lymphocytic leukemia; chloroma; acute myelogenous leukemia Cutis 102:266,271–272, 2018; acute myelomonocytic leukemia AAD Annual Meeting 1999: Gross and Microscopic Dermatology; Med J Malaysia 58:102–104, 2003 Lymphoma, including cutaneous T-cell lymphoma (CTCL) – often a sign of folliculotropic CTCL JAAD 73:976–986, 2015; JAAD 60:359–375, 2009; Eur J Dermatol 10:309–312, 2000; pilotropic (follicular) (folliculotropic) CTCL AD 144:738–746, 2008; AD 138:191–198, 2002; chronic lymphocytic leukemia with B-cell lymphoma Personal Observation; Sezary syndrome with large-cell transformation JAMADerm 150:210–212, 2014; CD8+ small/ medium sized pleomorphic T-cell lymphoma BJD 170:204–206, 2014 Metastatic breast carcinoma JAAD 37:129–130, 1997 Myelodysplastic syndrome – subcutaneous eosinophilic necrosis with myelodysplastic syndrome JAAD 20:320, 1989 Plasmacytomas – disseminated extramedullary plasmacytomas JAAD 14:335, 1986 Subcutaneous eosinophilic necrosis with myelodysplastic syndrome JAAD 20:320, 1989 Trichoepitheliomas – multiple (trichoepitheliomatous infiltration) Indian Dermatology Online J 8:358–360, 2017; Am J Dermatopathol 24:402–405, 2002; Ped Derm 10:252–5, 1993; giant facial nodules BJD 149:674–675, 2003; familial Indian Dermatol J Online 8:358–360, 2017

PARANEOPLASTIC Acanthosis nigricans, paraneoplastic Secondary hypertrophic osteoarthropathy (pachydermoperiostosis-­ like) – associated with solitary fibrous tumor of the lung JAAD 57:S106–110, 2007; adenocarcinoma of the lung Respiration 79:250–254, 2010

PHOTODERMATOSES Actinic prurigo Int J Dermatol 51:234–236, 2012; Ped Derm 23:97–98, 2006

Nodular xanthomatosis, infancy Ped Derm 4:242–246, 1987

Actinic reticuloid JAAD 38:877–905, 1998; AD 115:1078–1083, 1979

Scleredema diabeticorum

Chronic actinic dermatitis

NEOPLASTIC

PRIMARY CUTANEOUS DISEASES

Carcinoid syndrome JAMADerm 153:925–926, 2017; Actas Dermosifiliogr 101:542–546, 2010

Acne rosacea Australas J Dermatol 58:72–73, 2017

Epidermal inclusion cysts, multiple – personal observation

Pityriasis rosea – personal observation

Cryoglobulinemia – monoclonal, type I

577

Darier's disease Case Rep Dermatol 11:327–333, 2019

Epidermal nevi Ped Derm 3:69–74, 1985 Hair follicle hamartoma Hypereosinophilic syndrome Indeterminate dendritic cell tumor Kaposi’s sarcoma

SYNDROMES Carcinoid syndrome Centrofacial trichoblastomatosis – leonine facies, cobblestoning of glabella and nose, eyebrow alopecia BJD 169:224–226, 2013

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Infantile systemic hyalinosis Ped Derm 9:255–258, 1992

Darier’s disease JAAD Case Rep 4:262–266, 2018

KID syndrome – keratosis, ichthyosis, deafness syndrome – fixed orange, symmetrical hyperkeratotic plaques of the scalp, ears, and face with perioral rugae; aged or leonine facies; erythrokeratoderma-like; later hyperkeratotic nodules develop Ped Derm 17:115–117, 2000; Ped Derm 13:105–113, 1996; BJD 94:211–217, 1976

Eruptive hypomelanosis JAMADerm 150:1197–1201, 2014

Lipoid proteinosis

Idiopathic guttate hypomelanosis Am J Clin Dermatol 17:403–411, 2016

Mucolipidoses (pseudo-Hurler polydystrophy) BJD 130:528–533, 1994

Familial white lentigines Flat warts Frictional lichenoid dermatosis Ichthyosis en confetti

In association with keratosis punctata

Mucopolysaccharidoses (Hurler’s, Hurler-Scheie, Sanfilippo, Morquio, Maroteaux-Lamy, Sly syndromes) – coarse facies

Leukoderma punctata following PUVA therapy

Multicentric reticulohistiocytosis JAAD 49:1125–1127, 2003; Indian J Lepr 60:604–608, 1988; JAAD 11:713–723, 1984; masquerading as lepromatous leprosy Intern Med 51:2069–2070, 2012

Lymphoma – cutaneous T-cell lymphoma, hypopigmented (CD8+)

Neurofibromatosis Osteopathia striata syndrome Clin Ped (Phil)19:369–373, 1980 Pachydermoperiostosis (Touraine-Solente-Gole syndrome) BMJ Case Rep Jan 23, 2012:bcr1020115057; Dermatol Surg 31(pt 1)1465–1467, 2005; AD 124:1831–1834, 1988; JAAD 31:941–953, 1994 Polyostotic fibrous dysplasia of the facial bones Int J Oral Surg 10(Suppl 1):47–51, 1981 Premature familial sebaceous hyperplasia JAAD 37:996–998, 1997 Setleis syndrome (focal facial dermal dysplasia with other facial anomalies) – autosomal recessive; aged leonine appearance, bitemporal scar-like defects, absent or multiple rows of upper eyelashes, eyebrows slanted up and out, absent eyebrows, puckered periorbital skin, scar-like median furrow of chin Ped Derm 21:82–83, 2004; Scand J Plast Reconstr Surg Hand Surg 35:107– 111, 2001; BJD 130:645–649, 1994; AD 110:615–618, 1974; Br J Derm 84:410–416, 1971; Pediatrics 32:540–548, 1963 Steatocystoma multiplex Winchester syndrome – annular and serpiginous thickenings of skin; arthropathy, gargoyle-like face, gingival hypertrophy, macroglossia, osteolysis (multilayered symmetric restrictive banding), generalized hypertrichosis, very short stature, thickening and stiffness of skin with annular and serpiginous thickenings of skin, multiple subcutaneous nodules JAAD 50:S53–56, 2004

VASCULAR Angiolymphoid hyperplasia with eosinophilia Cutis 72:323–326, 2003 Port wine stain (nevus flammeus) Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.114

Lichen sclerosus et atrophicus Morphea Pityriasis lichenoides chronica, hypochromic variant Clin Exp Dermatol 3:85, 1978 Tuberous sclerosis Sem Cut Med Surg 16:30–35, 1997 Vitiligo, guttate Xeroderma pigmentosum

LEUKONYCHIA  OTAL; PARTIAL; PUNCTATE, LONGITUDINAL, T STRIATE, OR TRANSVERSE

CONGENITAL DISEASES Leukonychia – congenital JAAD 39:509–512, 1998; congenital leukonychia totalis – usually autosomal dominant; mutation in PLCD1 Case Rep Dermatol 10:82–88, 2018

DRUGS Acitretin – transverse leukonychia Int J Dermatol 53:e221–222, 2014 Chemotherapy – transverse striated leukonychia; bleomycin, 5-­fluorouracil, cyclophosphamide, dacarbazine, docetaxel, vorinostat, vincristine, hydroxyurea, etoposide, daunorubicin Int J Dermatol 42:468–469, 2003; South Med J 90:395–398, 1997 Sulfathiazole Dermatol Clin 6:305–313, 1988 Trazodone Dermatol Clin 6:305–313, 1988 Vorinostat AD 145:1338–1339, 2009

EXOGENOUS AGENTS

LEUKODERMA, GUTTATE

Nitric acid – diffuse leukonychia Semin Dermatol 10:17–20, 1991

Acquired brachial cutaneous dermatosis JAAD 42:680–684, 2000

Concentrated sodium chloride – diffuse leukonychia Semin Dermatol 10:17–20, 1991

Acral speckled hypomelanosis JAAD Case Rep 5:770–772, 2019

Nitrite solution – diffuse leukonychia Semin Dermatol 10:17–20, 1991

Chemical leukoderma Chromosomal abnormalities Clear cell papulosis BJD 138:678–683, 1998 Confetti-like leukoderma Congenital guttate leukoderma Osaka City Med J 51:33–36, 2005

INFECTIONS AND INFESTATIONS HIV infection Actas Sermosifillogr 103:934–935, 2012 Leprosy Mycobacterium tuberculosis Dermatol Clin 6:305–313, 1988

Leukonychia Onychomycosis – superficial white onychomycosis – Trichophyton rubrum, T. mentagrophytes, Aspergillus species, Acremonium species (A. strictum), Fusarium solani, Onychocola canadensis AD 140:696–701, 2004; JAAD 36:29–32, 1997; proximal white onychomycosis due to Fusarium falciforme BJD 173:253–255, 2015 Sepsis – transverse white nail bands Typhoid fever Dermatol Clin 6:305–313, 1988

579

Hailey-Hailey disease (longitudinal leukonychia) AD 146:1204, 2010; Hautarzt 43:451–452, 1992 Idiopathic acquired leukonychia totalis Ped Derm 31:404–405, 2014 Keratosis follicularis spinulosa decalvans – and leukonychia West Indian Med J 63:552–553, 2014 Leukonychia totalis – longitudinal half and half nails, true leukonychia Skin Appendage Disord 1:185–186, 2016; BJD 167:946– 949, 2012; BJD 152:401–402, 2005

Flag sign – white-red bands; leprosy, post-heart transplant surgery Dermatol Online J March 2019

Mee's lines (white transverse bands) seen with arsenic poisoning, pellagra, malnutrition, typhoid fever, Hodgkin's disease, renal failure, renal allograft rejection, and myocardial infarction Dermatol Clin 6:305–313, 1988

Transverse striated leukonychia – after febrile illness

Psoriasis Dermatol Clin 6:305–313, 1988

Ulcerative colitis Semin Dermatol 10:17–20, 1991

Vitiligo An Bras Dermatol 91:442–445, 2016

METABOLIC DISEASES

SYNDROMES

Acute disease – transverse leukonychia – Kawasaki’s disease, pleural empyema, renal transplant

Acrokeratosis verruciformis Genetic Skin Disorders, Second Edition, 2010,pp.54–57

Anemia – apparent leukonychia

Bart-Pumphrey syndrome – knuckle pads, total leukonychia, mixed hearing loss Ped Derm 31:404–405, 2014;

INFLAMMATORY DISEASES

Congestive heart failure – Terry’s nails (proximal 80% of nail plate is white, distal 20% is pink) white lunulae Hemochromatosis – leukonychia AD 113:161–165, 1977; Medicine 34:381–430, 1955 Hypoalbuminemia – Muehrcke’s lines (thin white parallel transverse bands) AD 143:815–816, 2007 Liver disease – leukonychia; white lunulae Terry’s nails Pellagra – leukonychia Selenium deficiency BJD 177:e72, 2017; Crohn’s disease with selenium deficiency – true leukonychia of nail plate JAMADerm 150:780–781, 2014 Terry’s nails – apparent leukonychia (diffuse whitening of the nail bed) Lancet 1:757–759, 1954 Thyroid acropachy – personal observation Zinc deficiency – leukonychia Muehrcke’s paired lines; bilateral longitudinal true leukonychia Indian J Prev Med 7:118, 2016

NEOPLASTIC DISEASES Onychopapilloma – longitudinal leukonychia JAAD 63:541–542, 2010 Squamous cell carcinoma BJD 156:871–874, 2007 Sezary syndrome J Cut Med Surg 23:380–387, 2019

PARANEOPLASTIC DISORDERS Leukonychia and internal malignancy Dermatol Clin 6:305–313, 1988

PRIMARY CUTANEOUS DISEASES Acrokeratosis verruciformis of Hopf Alopecia areata – white lunulae; punctate leukonychia Int J Dermatol 57:776–783, 2018 Darier’s disease – white bands Dermatol Clin 6:305–313, 1988 Familial leukonychia -

JAAD 51:292, 2004; NEJM 276:202–207, 1967 Bauer syndrome – leukonychia totalis Ped Derm 31:404–405, 2014 Congenital keratosis palmaris et plantaris-deafness-leukonychia totalis syndrome Indian J Dermatol Venereol Leprol 78:107–108, 2012 Flotch syndrome – leukonychia totalis Ped Derm 31:404–405, 2014 Hereditary palmoplantar keratoderma with deafness Genetic Skin Disorders, Second Edition, 2010,pp.58–60 Knuckle pads-leukonychia-deafness syndrome leukonychia totalis Ped Derm 31:404–405, 2014 LEOPARD syndrome – leukonychia totalis Ped Derm 31:404–405, 2014 Heimler syndrome – leukonychia totalis, deafness, enamel dysplasia Int J Dermatol 155:e169, 2016; Ped Derm 31:404–405, 2014; J Med Genet 36:941–943, 1999 Leukonychia totalis, sebaceous cysts, renal calculi (Buschkell-Gorlin syndrome) Ped Derm 31:404–405, 2014; AD 111:899–901, 1975 Leukonychia and peptic ulcer disease and cholelithiasis NY State J Med 1982:1797–1800 Leukonychia, keratoderma and hypotrichosis BJD 133:636–638, 1995; palmoplantar keratoderma and atrophic fibrosis; GJA1 mutation Hum Mol Genet 24:65–64, 2015; Ped Derm 31:404–405, 2014 Leukonychia, koilonychia, multiple pilar cysts Acta DV 95:249–250, 2015 Leukonychia and pili torti Cutis 1985:533–534 Leukonychia, congenital hypoparathyroidism; hypoparathyroidism, onychorrhexis, and cataracts, LEOPARD syndrome Int J Derm 29:535–541, 1990 Lowry-Wood syndrome – leukonychia totalis Ped Derm 31:404–405, 2014 POEMS syndrome (osteosclerotic myeloma) (Crow-Fukase syndrome, Takatsuki syndrome) (PEP syndrome – plasma cell dyscrasia, endocrinopathy, polyneuropathy) – plethora, angiomas (cherry, globular, glomeruloid) presenting as red nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, scleroderma-like changes, either generalized or localized (legs), hyperhidrosis, clubbing, leukonychia, papilledema, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss,

580 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias; osteosclerotic myeloma (IgG or IgA lambda) bone lesions, progressive symmetric sensorimotor peripheral polyneuropathy, hypothyroidism, and hypogonadism; peripheral edema, thrombocytosis, cutaneous angiomas, blue dermal papules associated with Castleman’s disease (benign reactive angioendotheliomatosis), maculopapular brown-violaceous lesions, purple nodules; papilledema AD 146:615–623, 2010; JAAD 58:671–675, 2008; Blood Reviews 21:285–299, 2007; JAAD 55:149–152, 2006; JAAD 44:324–329, 2001, JAAD 40:808–812, 1999; AD 124:695– 698, 1988, Cutis 61:329–334, 1998; JAAD 21:1061–1068, 1989; JAAD 12:961–964, 1985; Nippon Shinson 26:2444–2456, 1968

JAAD 36:928–934, 1997

Trichorhinophalangeal syndrome type I – autosomal dominant; slow growing hair, receding frontotemporal hairline with high bossed forehead; thin nails, koilonychias, leukonychia, facial pallor, pear-shaped nose with bulbous nose tip, wide long philtrum, thin upper lip, triangular face, receding chin, tubercle of normal skin below the lower lip, protruding ears, distension and deviation with fusiform swelling of the PIP joints; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, lateral eyebrows sparse and brittle,, dense medially, bone deformities (hands short and stubby), cone-shaped epiphyses of bones of hand, lateral deviation of interphalangeal joints, flat feet, hip malformations, high-arched palate, supernumerary teeth, dental malocclusion, mild short stature; hypotonia, deep voice, recurrent respiratory infections, hypoglycemia, diabetes mellitus, hypothyroidism, decreased growth hormone, renal and cardiac defects, mutation in zinc finger nuclear transcription factor (TRPS1 gene) Ped Derm 26:171–175, 2009; Ped Derm 25:557–558, 2008; BJD 157:1021–1024, 2007; AD 137:1429–1434, 2001; JAAD 31:331–336, 1994; Hum Genet 74:188–189, 1986; Helv Paediatr Acta 21:475–482, 1966

Chronic mucocutaneous candidiasis – crusted plaques, cicatricial alopecia, leukoplakia, dystrophic nails Ped Derm 34:609–611, 2017; autosomal dominant chronic mucocutaneous candidiasis NEJM 365:54–61, 2011

Woolly hair and striate palmoplantar keratoderma – mutation in KANK2; leukonychia, pseudoainhum of 5th toe; no cardiac abnormalities Ped Derm 34:724–725, 2017

TOXINS Arsenic – Mee’s lines of nails BJD 149:757–762, 2003 Heavy metal poisoning Dermatol Clin 6:305–313, 1988 Selenium toxicity – transverse white nail bands JAAD 63:168–169, 2010 Strontium Clin Pediatr 44:531–533, 2005

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis with oral lichenoid reaction to amalgam fillings (mercury) BJD 134:420–423, 1996; BJD 126:10–15, 1992; allergic contact dermatitis to cinnamon-flavored gum CARD9 (caspase recruitment, domain-containing protein 9) deficiency – mucocutaneous and central nervous system candidiasis of brain parenchyma or meninges Clin Inf Dis 59:81–84, 2014

Graft vs. host disease – thick white plaques of tongue; mimics oral lichen planus JAAD 72:690–695, 2015 Lupus erythematosus – discoid lupus erythematosus; ulcerations honeycomb plaques, hyperkeratosis, aphthous-like ulcers with white coating Dermatol Clin 21:63–78, 2003; BJD 121:727–741, 1989

DRUGS Allopurinol-induced lichen planus – personal observation Interferon – personal observation Lichen planus, drug induced Sem Cut Med Surg 34:161–170, 2015 Palifermin (keratinocyte growth factor – white tongue; prevents chemotherapy-induced mucositis) NEJM 360:e26, 2009 Tumor necrosis factor alpha antagonists – lichen planus-like eruptions JAAD 61:104–111, 2009

EXOGENOUS AGENTS Antiseptics Betel nut chewing – submucous fibrosis Cutis 71:307–311, 2003; JAAD 37:81–88, 1998 Mercury – lichenoid mucositis secondary to amalgam fillings with mercury

Thallium – transverse white nail bands

Mouthwashes (Listerine) – mouthwash-induced keratosis JAAD 58:151–157, 2008; Oral Surg 46:781, 1978

TRAUMA

Nicotine stomatitis – begins as erythema of hard palate; then progresses to grayish white nodular appearance Sem Cut Med Surg 34:161–170, 2015; Dermatol Clin 21:63–78, 2003

Minor trauma – horizontal leukonychia Dermatol Clin 33:243–255, 2015; Dermatol Clin 6:305–313, 1988; punctate leukonychia

Pipe smoking – benign keratosis of palate

Total skin electron beam irradiation – transient leukonychia J Eur Acad DV 25:115–117, 2011

Reverse smoking (India) – palate; snuff dipping and smokeless tobacco (tobacco pouch keratosis) – vestibule Dermatol Clin 21:63–78, 2003

VASCULAR DISORDERS

Skin grafts

Dissecting aortic aneurysm – transverse white nail bands Edema – apparent leukonychia Ischemia – white lunulae

Smokeless tobacco (tobacco chewing) keratosis Sem Cut Med Surg 34:161–170, 2015; JAAD 58:151–157, 2008 Viadent-associated leukokeratosis (sanguinaria extract) J Can Dent Assoc 56:41–47, 1990

Raynaud’s phenomenon Dermatol Clin 6:305–313, 1988 Vascular insufficiency – pale nail bed (apparent leukonychia)

INFECTIONS AND INFESTATIONS Bejel – endemic syphilis; mucous patch

LEUKOPLAKIA

Leukoplakia Candida – acute pseudomembranous candidosis (Candida leukoplakia); chronic hyperplastic candidiasis Oral Surg Oral Med Oral Pathol 56:388–395, 1983; chronic mucocutaneous candidiasis Ann Rev Med 32:491–497, 1981; oral candidiasis in chronic granulomatous disease, hyper IgE syndrome, immunodeficiency with thymoma, APECED syndrome, myeloperoxidase deficiency, selective IgA deficiency, severe combined immunodeficiency, adenosine deaminase deficiency, cellular immunodeficiency with immunoglobulins, bare lymphocyte syndrome, congenital thymic aplasia, DiGeorge’s syndrome, Nezelof’s syndrome, C3 deficiency, biotin-responsive multiple carboxylase deficiency Histoplasmosis Leishmaniasis (L. infantum) – leukoplakia of tongue AD 142:785– 786, 2006 Measles (Koplik’s spots)

581

Extramammary Paget’s disease – vulvar Dermatol Clinics 37:261– 267, 2019 Keratoacanthoma Leukokeratosis oris Leukoplakia – vulvar squamous epithelial hyperplasia with atypia; vulvar benign leukoplakia; HPV-associated sublingual leukoplakia BJD 158:644–646, 2008 Papillomas Porokeratosis of Mibelli Premalignant epithelial dysplasia Proliferative verrucous leukoplakia (hyperplasia) – expanding exophytic verrucous white plaques JAAD 81:59–71, 2019; AD 127:887–892, 1991; Oral Surg Oral Med Oral Pathol Oral Radiol Endod 60:285–298, 1985

Oral hairy leukoplakia – AIDS-associated lesion; also seen in transplant patients, leukemia, others; Epstein-Barr virus JAMADerm 154:1475–1476, 2018; Sem Cut Med Surg 34:161–170, 2015; JAAD 72:1–19, 2015; JAAD 22:79–86, 1990; also seen in immunosuppressed BJD 124:483–486, 1991 and immunocompetent patients Oral Surg Oral Med Oral Pathol 74:332–333, 1992

Pseudoepitheliomatous, micaceous, and keratotic balanitis JAAD 54:369–391, 2006

Scarlet fever – white coated tongue

Squamous cell carcinoma in situ – lip

Syphilis, secondary – mucous patch Clin Dermatol 38:160–175, 2020; Chang Gung Med J 25:683–688, 2002; resembling oral hairy leukoplakia JAAD 49:749–751, 2003; tertiary – atrophic glossitis; syphilitic leukoplakia of the dorsal tongue

Submucous fibrosis

Verrucae Dermatol Clin 21:63–78, 2003; condyloma acuminatum White strawberry tongue – personal observation

Squamous acanthoma J Oral Surg 41:114–116, 1986 Squamous cell carcinoma of lip Sem Cut Med Surg 34:161–170, 2015; vulvar JAAD 81:59–71, 2019

Verrucous carcinoma (oral florid papillomatosis) Dental J (Basel) 1267, 2019; Oral Oncol 29B:81–82, 1993 White sponge nevus – of tongue; autosomal dominant; buccal mucosa bilaterally, benign Dental I (Basel) March 7, 2019; Sem Cut Med Surg 34:161–170, 2015; BJD 165:448–451, 2011; Ped Derm 27:100–101, 2010; mutation in keratin 13; BJD 159:974–975, 2008; Ped Derm 25:116–117, 2008; AD 117:73–76, 1981

INFILTRATIVE DISEASES Amyloid – white gingival papules BJD 148:154–159, 2003

PARANEOPLASTIC DISEASES

Langerhans cell histiocytosis Curr Prob in Derm VI:1–28, 1994

Paraneoplastic pemphigus, lichenoid variant JAAD 56:153–159, 2008

METABOLIC DISEASES Fanconi’s anemia – autosomal recessive; dyschromatosis; oral leukoplakia, oral and vulvar squamous cell carcinoma, short stature, absent radii, bone marrow failure, endocrine abnormalities, café au lait macules, guttate hypopigmentation, intertriginous hyperpigmentation, broad nose, epicanthal folds, micrognathia JAAD 54:1056– 1059, 2006

PRIMARY CUTANEOUS DISEASES

Liver failure, chronic

Darier's disease Br Dent J 171:133–136, 1991

Macroglobulinemia

Epidermolysis bullosa, Herlitz, junctional type Ped Derm 18:217– 222, 2001

Renal failure, chronic Riboflavin deficiency Sideropenic dysphagia

NEOPLASTIC DISEASES Acquired dyskeratotic leukoplakia AD 124:117–120, 1988 Actinic cheilitis Bowen’s disease Clear cell adenocarcinoma Dysplasia Sem Cut Med Surg 34:161–170, 2015 Epidermal nevus Erythroleukoplakia (speckled leukoplakia)

Aphthosis – with pseudomembranes Benign alveolar ridge keratosis (oral lichen simplex chronicus) – slightly rough papule or plaque on retromolar pad in older men JAAD 58:151–157, 2008

Focal oral epithelial hyperplasia (Heck’s disease) Furred tongue Geographic tongue Sem Cut Med Surg 34:161–170, 2015 Hereditary palmoplantar keratoderma (Unna-Thost) with oral keratosis or periodontosis Idiopathic keratosis Leukoedema Sem Cut Med Surg 34:161–170, 2015; JAAD 58:151–157, 2008; Dermatol Clin 21:63–78, 2003; Community Dent Oral Epidemiol 9:142–146, 1981; AD 116:906–908, 1980 Lichen planus Sem Cut Med Surg 34:161–170, 2015; J Oral Pathol 14:431–458, 1985; – leukoplakia of tongue BJD 158:573–577, 2008; vulvar lichen planus mimicking leukoplakia AD 125:1677– 1680, 1989; erosive lichen planus

582

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Lichen sclerosus et atrophicus – bluish-white plaques of mouth; may mimic lichen planus Oral Surg Oral Med Oral Pathol 88:702– 706, 1999; Oral Surg Oral Med Oral Pathol 84:165–170, 1997; BJD 131:118–123, 1994; J Oral Pathol Med 22:374–377, 1993; Br J Oral Maxillofac Surg 89:64–65, 1991; AD 76:56–58, 1957; wrinkled lesions, atrophic vulvar with shrinkage Cutis 67:249–250, 2001; Trans St John’s Hosp Dermatol Soc 57:9–30, 1971; involvement of lip, tongue, gingiva Ped Derm Meeting of AAD, March, 2000

ous horn of the lips JAAD 52:403–409, 2005; BJD 146:680–683, 2002; Oral Surg 50:250, 1980; Birth Defects 12:239–242, 1976; Arch Int Med 113:866–871, 1964 Grinspan’s syndrome – oral lichen planus, diabetes mellitus, hypertension

Lichen simplex chronicus, vulvar

Hereditary benign intraepithelial dyskeratoses (Witkop-von Sallmann syndrome) – conjunctivitis; leukoplakia of buccal mucosa, lips, tongue in Haliwa-Saponi Native Americans of North Carolina JAAD 77:809–830, 2017; JAAD 45:634–636, 2001; Arch Pathol 70:696–711, 1960

Linea alba Dermatol Clin 21:63–78, 2003

Hereditary mucoepithelial dysplasia BJD 153:310–318, 2005

Lichenoid verrucous leukoplakia Mal de Meleda

Howell-Evans syndrome (tylosis) – autosomal dominant; focal PPK; oral leukokeratosis, carcinoma of the esophagus

Materia alba – accumulation or aggregation of microorganisms, desquamated epithelial cell, blood cells, food debris adherent to plaques of teeth, gingival or dental appliance

Orphanet J Rare Diseases Sept 29, 2015; Curr Prob Derm 14:71–116, 2002; J Oral Pathol 3:62–70, 1974; Q J Med 155:317– 333, 1970; QJMed 27:413–429, 1958

Oral submucous fibrosis Oral Oncol 102:104550, 2020

Hyper IgE syndrome(Job’s syndrome) (Buckley’s syndrome) – papular, pustular, excoriated dermatitis of the scalp, buttocks, neck, axillae, groin; furunculosis; growth failure; dermatitis of face, behind ears, scalp, axillae, and groin; recurrent bacterial infections of skin with cold abscesses, contact urticaria, infections of nasal sinuses and respiratory tract J Pediatr 141:572–575, 2002; NEJM 340:692– 702, 1999; Curr Prob in Derm 10:41–92, 1998; Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983; Lancet 1:1013– 1015, 1966

Oral verruciform xanthoma Head Neck Pathol Jan2, 2020 Palmoplantar keratoderma – Unna-Thost disease Pityriasis rubra pilaris Pseudo-oral hairy leukoplakia JAAD 30:300–303, 1994 Psoriasis – annuli; white lesions of buccal mucosa Scand J Dent Res 92:50–54, 1984 Shedding oral mucosa Cutis 54:323–326, 1994 Verrucous hyperplasia – exophytic, occurring in submucous fibrosis J Oral Maxillofac Pathol 23:393–399, 2019

PSYCHOCUTANEOUS DISEASES Self-inflicted

SYNDROMES Clouston's syndrome (hidrotic ectodermal dysplasia) – autosomal dominant; palmoplantar hyperkeratosis, hair defects, nail dysplasia, leukoplakic lesions Oral Surg 57:258–262, 1984 Cole-Engmann syndrome – leukoplakia of the tongue J Oral Maxillofac Surg 57:1138–1141, 1999 Congenital plasminogen deficiency – autosomal recessive; chronic mucosal pseudomembranous lesions with white membranes of gingivae and eyelids; blepharitis, gingival hyperplasia, leukoplakia, ligneous conjunctivitis; thick nodular eyelids Ped Derm 448–451, 2009 Dyskeratosis benigna intraepithelialis mucosae et cutis hereditaria – conjunctivitis, umbilicated keratotic nodules of scrotum, buttocks, trunk; palmoplantar verruca-like lesions, leukoplakia of buccal mucosa, hypertrophic gingivitis, tooth loss J Cutan Pathol 5:105– 115, 1978 Dyskeratosis congenita (Zinsser-Engmann-Cole syndrome) – Xq28; leukoplakia of buccal mucosa and tongue and nail atrophy; DKC1 mutation; defective telomere maintenance; 30% malignant transformation BJD 178:335–349, 2018; JAAD 77:1194–1196, 2017; Ped Derm 28:464–466, 2011; oral bullae and erosions JAAD 74:437– 451, 2016; J Blood Med 5:157–167, 2014; Br J Haematol 145:164– 172, 2009; Semin Cut Med Surg 16:72–80, 1997; Rook p.415, 1998, Sixth Edition; J Med Genet 33:993–995, 1996; Dermatol Clin 13:33–39, 1995; BJD 105:321–325, 1981 Focal palmoplantar and oral mucosa (gingival) hyperkeratosis syndrome (MIM:148730) (hereditary painful callosities) – palmoplantar keratoderma, leukoplakia (gingival keratosis), and cutane-

Keratosis-ichthyosis-deafness (KID) syndrome – oral leukoplakia, reticulated severe diffuse hyperkeratosis of palms and soles, well-­marginated, serpiginous erythematous verrucous plaques, perioral furrows, leukoplakia, sensory deafness, photophobia with vascularizing keratitis, blindness Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990; JAAD 23:385–388, 1990; AD 123:777–782, 1987; AD 117:285–289, 1981 Olmsted syndrome – oral leukokeratosis, periorificial keratotic plaques; congenital diffuse sharply marginated transgradient keratoderma of palms and soles, onychodystrophy, constriction of digits, diffuse alopecia, thin nails, chronic paronychia, linear keratotic streaks, follicular keratosis, constriction of digits (ainhum), anhidrosis, small stature; differential diagnostic considerations include Clouston hidrotic ectodermal dysplasia, pachyonychia congenita, acrodermatitis enteropathica, Vohwinkel's keratoderma, mal de Meleda, and other palmoplantar keratodermas JAAD 53:S266–272, 2005; Ped Derm 21:603–605, 2004; Ped Derm 20:323–326, 2003; BJD 136:935–938, 1997; AD 132:797–800, 1996; JAAD 10:600–610, 1984 Oral florid papillomatosis Pachyonychia congenita – patchy oral leukokeratosis (milky leukoplakia; mutation in keratin 6A (KRT6A) Ped Derm 36:149–151, 2019; JAAD 77:809–830, 2017; Ped Derm 33:337–342, 2016; BJD 171:343–355, 2014; JAMADerm 150:146–153, 2014; JAAD 67:680–686, 2012; AD 147:1077–1080, 2011; BJD 160:1327–1329, 2009; Cutis 84:269–271, 2009; BJD 152:800–802, 2005; Clin Dermatol 23:6–14, 2005; JAAD 19:705–711, 1988 Plummer-Vinson syndrome (sideropenic dysphagia) – iron deficiency; hyperkeratotic lesions of oral mucosa Arch Int Med 155:2008–2011, 1995 Pseudoxanthoma elasticum – leukoplakia beneath the tongue Sweet’s syndrome – personal observation Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – white plaques of the tongue, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria

Linear Erythronychia 583 and mental and physical retardation JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997 X-linked agammaglobulinemia – oral ulcers, oral leukokeratosis BJD 178:335–349, 2018

Warty dyskeratoma

MULTIPLE Acantholytic dyskeratotic epidermal nevus

TOXINS Arsenic exposure, chronic J Occup Environ Med 55:59–66, 2013

Acantholytic epidermolysis bullosa Amyloidosis, primary Darier’s disease Erythema multiforme Indian J Dermatol 60:636, 2015

TRAUMA

Graft vs. host disease SKINMed9:327–329, 2011

Biting buccal mucosa (morsicatio buccarum et labiorum) (biting tongue)

Hailey-Hailey disease Dermatol Ther 25:603–611, 2012

Burns, thermal, chemical (aspirin, gasoline, rubbing alcohol, eugenol, lye, phenol)

Idiopathic polydactylous longitudinal erythronychia

Chronic chewing of lip, tongue or cheek – wedge shaped leukoplakia of cheek Dentures Frictional hyperkeratosis Sem Cut Med Surg 34:161–170, 2015; Dermatol Clin 21:63–78, 2003 Linea alba JAAD 58:151–157, 2008; Dermatol Clinics 21:63–78, 2005 Mechanical irritation; frictional keratosis (linea alba, lip, cheek, and tongue chewing) Morsicatio buccarum (chronic bite injury) – chewing lip, tongue, cheek JAAD 58:151–157, 2008 Radiation Seizure

LINEAR ERYTHRONYCHIA

Hemiplegia Lichen planus Dermatol Surg 42:310–319, 2016

LINEAR HYPOPIGMENTATION Allergic contact dermatitis to Spandex waist bands Basaloid follicular hamartoma syndrome – Blaschko-esque lesions of face Clin Exp Dermatol 30:30–34, 2005 CHILD syndrome Ped Derm 15:36–366, 1998 Curry-Jones syndrome – linear hypo- or hyperpigmented lesions, palmoplantar pitting, atrophoderma, hypertrichosis, trichoblastomas and nevus sebaceous, polydactyly of syndactyly, dysmorphic facies, macrocephaly, microcephaly, dental anomalies, craniosynostosis, anal stenosis, myofibromas and smooth muscle hamartomas, medulloblastomas, cerebral malformations, developmental delay, cataracts, microphthalmia, coloboma, glaucoma, cryptorchidism; mutation in SMOc.1234C>T BJD 182:212–217, 2020 Epidermal nevus

JAAD 64:167–174, 2011; Am J Clin Dermatol 12:217–231, 2011

SINGLE Acquired digital arteriovenous malformation J Dermatol 46:e88–89, 2019 Basal cell carcinoma Benign vascular proliferation (increased glomus bodies) Bowen’s disease Capillary hemangioma Australas J Dermatol 58:e255–256, 2017 Cirsoid aneurysm Glomus tumor Hemiplegia Leiomyoma J Drugs Dermatol 18:465–467, 2019 Lichen planus Melanoma

Goltz’s syndrome (focal dermal hypoplasia) Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia, coloboma; mutation in SMOc.1234C>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hypomelanosis of Ito – lines of Blaschko Incontinentia pigmenti, fourth stage Intralesional or intra-articular corticosteroids Rheumatol Clin 15:e72–73, 2019; J Drugs Dermatol 8:492–493, 2009

Myxoid cyst Dermatol Ther 25:603–611, 2012

Leprosy – linear tuberculoid leprosy Ann Dermatol Venereol 14:266–269, 2015

Neurofibroma Dermatol Ther 25:603–611, 2012

Lichen striatus Eur J Dermatol 10:536–539, 2000

Onychopapilloma J Eur Acad DV 32:2025–2030, 2018

Linear atrophoderma, congenital Ped Derm 22:350–354, 2005

Sarcoidosis Skin Appendage Disord 4:156–159, 2018 Squamous cell carcinoma Dermatol Ther 25:603–611, 2012

Linear keratosis follicularis and linear basaloid follicular hamartoma with guttate macules

Subungual acantholytic dyskeratotic acanthoma Pathology 50:582–584, 2018

Morphea Ped Derm 24:147–150, 2007

Verruca vulgaris

Menkes’ kinky hair syndrome (female carrier)

584 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – autosomal dominant; basal cell carcinomas, basaloid follicular hamartomas, linear hypo- or hyperpigmented lesions; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microphthalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors (fibromas), mesenteric cysts, cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism, BJD 182:212–217, 2020; BJD 165:30–34, 2011; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908– 912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004 Nevus comedonicus Nevus depigmentosus PHACES syndrome BJD 155:192–194, 2006 Pigmentary mosaicism Am J Med Genetics A 137A:313–322, 2005 Scarring Scleroderma, linear Segmental vitiligo Segmental ash leaf macule

fissures of radial and palmar surfaces of fingers Medicine 70:360– 374, 1991; linear calcinosis Dermatology 219:155–157, 2009 Graft vs. host disease – lichenoid graft vs. host reaction JAAD 37:1004–1006, 1997; AD 130:70–72, 1994; South Med J 87:758– 761, 1994; linear and curvilinear morphea-like chronic GVHD AD 144:1229–1231, 2008; linear grooving of sclerodermoid skin JAAD 66:515–532, 2012; erythronychia – due to graft vs. host disease SKINmed 9:327–329, 2011 Linear IgA disease (spontaneous) – bullae in linear array (string of pearls) BJD 169:1041–1048, 2013 Linear melorheostotic scleroderma – indurated skin overlying bony lesions; rare form of hyperostosis (endosteal bone densities resembling candle wax); pain and stiffness, contracture and deformity; cutaneous changes overlying these bony lesions are of two types, 1) proliferation and malformation of blood vessels and lymphatics and 2) sclerodermatous changes; linear melorheostotic scleroderma with hypertrichosis sine melorheostosis BJD 141:771– 772, 1999; AD 115:1233–1234, 1979; BJD 86:297–301, 1972 Lupus erythematosus – bullous lupus erythematosus J Med Case Rep 13:350, 2019; JAAD 57:690–699, 2007; Ped Derm 12:138–144, 1995; linear lupus profundus JAAD 24:871–874, 1991; neonatal lupus Ped Derm 22:240–242, 2005 Morphea – including morphea with mucin; linear morphea BJD 169:1265–1271, 2013; Semin Cutan Med Surg 18:210–225, 1999; Semin Cutan Med Surg 17:27–33, 1998; Int J Derm 35:330–336, 1996; nodular morphea (Addisonian keloid) Int J Dermatol 38:529–530, 1999; linear erythema of the forehead as early presentation of en coup de sabre Clin Exp Dermatol 45:470–471, 2020;

Vitiligo, Koebnerized

en coup de sabre Ped Derm 29:738–748, 2012; JAAD 56:257–263, 2007; linear red brown macules Ped Derm 35:685–687, 2018

LINEAR LESIONS

Pemphigus erythematosus localizing in a scar Cutis 64:179–182, 1999; pemphigus vulgaris in a scar Dermatologica 182:191–192, 1991; pemphigus vulgaris Dermatologica 179:135–136, 1989

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Pemphigus foliaceus of children JAAD 46:419–422, 2002; Ped Derm 3:459–463, 1986

Adult-onset Still’s disease, atypical – flagellate erythema JAAD 73:294–303, 2015; Autoimmun Highlights 6:39–46, 2015; BJD 145:187–188, 2001; Still’s disease (juvenile rheumatoid arthritis) – linear urticarial-like lesions; linear pigmentation Dermatology 202:333–335, 2001; Arthr Rheum 25:647–654, 1982

Rheumatoid arthritis – linear subcutaneous bands Am J Med 54:445–452, 1973; Ann Int Med 63:134–140, 1965; rheumatoid nodules; palisaded neutrophilic granulomatous dermatitis of rheumatoid arthritis (rheumatoid neutrophilic dermatosis) (interstitial granulomatous dermatitis) – vertical symmetrical linear cords or bands of median axillary line JAAD 53:191–209, 2005; JAAD 47:251–257, 2002; JAAD 45:286–291, 2001;

Allergic contact dermatitis to poison ivy, hair dye, tape, hat or wrist band; Paederus dermatitis Cutis 72:385–388, 2003; to cashew apple Cutis 92:174–176, 2013; Parthenium dermatitis – deck chair sign JAMADerm 151:906–907, 2015; mango dermatitis – personal observation; octyl cyanoacrylate Dermatitis 30:314, 322, 2019 Cold urticaria – ice cube test Combined immunodeficiency disease – red plaques with linear scars JAAD 25:761–766, 1991 Dermatitis herpetiformis – linear petechiae of fingertips Dermatology 227:1–4, 2013 Dermatomyositis – centripetal flagellate erythema Ped Derm 35:676–677, 2018; J Rheumatol 26:692–695, 1999; presenting as a pityriasis rubra pilaris-like eruption (type Wong dermatomyositis) (follicular hyperkeratotic linear lesions of backs of hands and feet, palms, soles in Chinese patients) – linear lesions over bony prominences JAAD 43:908–912, 2000; BJD 136:768–771, 1997; BJD 81:544–547, 1969; hyperpigmented linear streaks over extensor tendon sheaths in dark-skinned individuals BJD 132:670– 671, 1995; linear violaceous edematous streaks of trunk Clin Exp Dermatol 21:440–441, 1996; mechanics’ hands – hyperkeratotic

Ann DV 117:746–748, 1990; intravascular or intralymphatic histiocytosis in rheumatoid arthritis – linear indurated erythema and grouped papules JAAD 50:585–590, 2004 Scleroderma, including scleroderma as plasma cell panniculitis JAAD 21:357–360, 1989; perioral rhagades Serum sickness – linear purpura along margins of hands and feet JAAD 13:411–417, 1985

CONGENITAL ANOMALY Amniotic band syndrome – linear erosions, crusts and constrictions AD 130:1055–1060, 1994; Cutis 44:64–66, 1989 Aplasia cutis congenita – isolated lesion; of face Aplasia cutis congenita in surviving co-twins Ped Derm 18:511–515, 2001 Aplasia cutis congenita type V with fetus papyraceus or placental infarcts – linear and stellate atrophy Cutis 64:104–106, 1999; cutaneous ulcers, linear atrophic scars, atrophic scars of scalp,

Linear Lesions

585

dystrophic nails Ped Derm 32:858–861, 2015; symmetric linear erosions of extremities Ped Derm 28:467–469, 2011

1999; scaly linear erythema of dorsa of hands with atrophy and telangiectasia (dermatomyositis-like) JAAD 48:439–441, 2003

Aplasia cutis congenita, reticulolinear – of face and neck as manifestation of Xp22 deletion syndrome BJD 138:1046–1052, 1998

Bone marrow transplant – unilateral lichenoid eruption after bone marrow transplant JAAD 28:888–892, 1993

Aplasia cutis congenita type II – scalp ACC with associated limb anomalies; hypoplastic or absent distal phalanges, syndactyly, club foot, others; linear fibrous bands of the extremities Ped Derm 19:326–329, 2002

Corticosteroids – rosacea; intralesional corticosteroids – linear hypopigmentation AD 121:26, 1985; perilesional linear atrophy JAAD 19:537–541, 1988; linear atrophy due to intralesional corticosteroid injections of de Quervain tenosynovitis Cutis 73:197–198, 2004

Acquired raised bands of infancy – associated with amniotic bands Ped Derm 22:346–349, 2005

Coumarin – linear localized coumarin necrosis Dermatologica 168:31–34, 1984

Branchial cleft cyst and sinus tract Ped Derm 2:318–321, 1985

Drug eruptions, linear Eur J Dermatol 11:122–123, 2001

Congenital constriction band of the trunk (variant of amniotic band syndrome) Ped Derm 14:470–472, 1997

Fetal hydantoin syndrome – single palmar crease

Congenital curvilinear palpable hyperpigmentation JAAD 53:S162– 164, 2005

Fixed drug eruption

Ectopic meningothelial hamartoma – white linear plaque of occipital-­posterior scalp; may be orange or yellow Ped Derm 34:99–100, 2017; Ped Derm 31:208–211, 2014; Ped Der 28:677– 680, 2011; Am J Surg Pathol 14:1–11, 1980   Differential diagnosis:   Angiosarcoma    Membranous aplasia cutis congenita   Atretic meningocele   Epithelioid hemangioma    Giant cell fibroblastoma   Hypertrophic scar    Intravascular papillary endothelial hyperplasia    Spindle cell hemangioendothelioma Facial fusion defect (focal preauricular dermal dysplasia) (form of aplasia cutis congenital) – linear array of white atrophic patches of lateral cheeks Ped Derm 25:344–348, 2008 Graft-like plantar lesion JAAD 40:769–771, 1999 Horizontal neonatal linear hyperpigmentation of creases of abdomen and knees Median raphe cysts of the ventral penis – yellow cystic papules Ped Derm 27:667–669, 2010; differential diagnosis includes epidermoid or dermoid cysts, urethral diverticulosis, apocrine hidrocystoma

Fetal trimethadione syndrome – single palmar crease Gefitinib – streaky hyperpigmented eroded plaques; necrolytic migratory erythema-like JAMADerm 152:947–948, 2016 Methotrexate-related lymphoproliferative disorder – linear perilymphatic nodules of leg; linear bands; ulcerated and non-ulcerated red nodules JAAD 61:126–129, 2009 Morbilliform drug eruption under tape – personal observation Norplant implantation site OnabotulinumtoxinA – localized pruritus with hypopigmented linear streaks J Drugs Dermatol 14:199–200, 2014 Vancomycin-induced linear IgA disease – under tape JAAD 62:898–899, 2010

DEGENERATIVE DISORDERS Digital myxoid cyst – longitudinal linear groove Dermatol Clin 33:243–255, 2015

EXOGENOUS AGENTS Agave americana (century plant) dermatitis – linear purpura Cutis 72:188–190, 2003

Median raphe cyst of the scrotum and perineum JAAD 55:S114– 115, 2006

Aluminum-zirconium complex – linear axillary papules JAAD 37:496–498, 1997

Midline cervical cleft – atrophic linear lesion AD 141:1161–1166, 2005

Band-Aid reaction – personal observation

Preauricular skin defects AD 133:1551–1554, 1997

Bovine collagen, injectable – granulomatous allergic reaction; linear red plaques of nasolabial folds JAAD 64:1–34, 2011

Sucking blisters – linear erosions Supraumbilical mid-abdominal raphe Ped Derm 10:69–70, 1993 Trisomy 8 – deep vertical creases of soles Trisomy 9 syndrome

Beryllium dermatitis – linear papules JAAD 49:939–941, 2003

Blood pressure cuff irritant dermatitis; petechiae – personal observation Buttercup irritant contact dermatitis – protoanemonin Contact Dermatitis 20:63–78, 2009 Cocaine injection nodules JAAD 21:570–572, 1989

DEGENERATIVE DISORDERS

Copper bracelet – green skin – personal observation

Neuropathic hands – personal observation

Copper eyeglass frames – green skin Coral dermatitis

DRUG-INDUCED Acral dysesthesia syndrome – accentuation along Wallace’s line Anabolic steroids – linear keloids Cutis 53:41–43, 1994 Bleomycin – flagellate erythema and hyperpigmentation Clin Exp Dermatol 16:216–217, 1991; AD 123:393–398, 1987; palmar creases JAAD 40:367–398, 1999; limited to striae JAAD 28:503– 505, 1993; linear papules and red macules JAAD 40:367–398,

Fetal alcohol syndrome – single palmar crease Fiberglass dermatitis – linear erosions; also urticaria, petechiae, purpura, telangiectasia, erythema multiforme-like, and nummular eczema-like lesions AD 130:787–792, 1994 Jellyfish, coral, and sea urchin spines – pruritic lichenoid papules and plaques; linear flagellate patterns Metal sutures

586 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Norplant implantation Paraphenylenediamine in cosmetic strings – linear depigmentation JAAD 61:909–910, 2009 Pili migrans – linear and serpiginous red line of sole Ped Derm 35:251–252, 2018 Senneca laxative – blistering erosive diaper dermatitis; diamondshaped erosion of buttocks with linear borders aligning with diaper edge; spares perianal area and gluteal cleft AD 148:402–404, 2012; Pediatrics 107:178–179, 2001 Shiitake mushroom dermatitis – linear and flagellate lesions Dermatitis 29:43–44, 2018; Dermatitis 21:290–291, 2010; AD 144:1241–1242, 2008; AD 143:1461–1462, 2007; Contact Dermatitis 27:65–70, 1992

Herpes simplex – linear intertrigo (knife cut sign) Clin Exp Dermatol 35:557–558, 2010; linear distribution on face; herpetic geometric glossitis (linear tongue fissures in HIV, other immunosuppressed patients) JAAD 61:139–142, 2009; Am J Clin Oncol 20:567–568, 1997; South Med J 88:1231–1235, 1995; NEJM 329:1859–1860, 1993 eczema herpeticum Herpes zoster of S1 dermatome – long linear and serpiginous erythematous plaque of upper and lower leg NEJM 370:20131, 2014 Jellyfish sting, including Portuguese man o’war sting Larva currens (Strongyloides) Clin Inf Dis 66:1636–1638, 2018; Dermatol Clin 7:275–290, 1989; AD 124:1826–1830, 1988 Leeches

Silicone – linear edema, nodularity, scarring, and bound-down skin due to leakage of silicone breast implant AD 131:54–56, 1995

Leishmaniasis – post kala-azar dermal leishmaniasis; Koebnerized papules BJD 143:136–143, 2000

Smoker’s face – linear wrinkling and atrophy AD 128:255–262, 1992

Leprosy – borderline lepromatous leprosy – linear, annular, and serpiginous plaques of cheek Clin Inf Dis 68:1241–1243, 2019; visible and palpable nerves including posterior auricular nerve – thickening of peripheral nerves can occur in all forms of leprosy Int J Lepr Other Mycobact Dis 62:37–42, 1994; localized linear lesions of lepromatous leprosy Indian J Lepr 73:343–348, 2001; differentiate from palpable peripheral nerves of hereditary sensory motor neuropathy type III; amyloidosis

Sock line bands Ped Derm 28:83–84, 2011 Spandex waistband depigmentation – personal observation Suture material – extrusion of undigested suture material; foreign body granulomas along suture line

INFECTIONS AND INFESTATIONS AIDS (HIV) – linear excoriations; linear gingival erythema of HIV disease Clin Oral Invest; Springer Verlag, 2008; Topics in HIV Medicine 13:143–148, 2006

Loiasis – linear cord BJD 145:487–489, 2001; Blaschko Int J Dermatol 58:729–732, 2019

Bacterial dissection Cutis 51:43–44, 1993

Lymphogranuloma venereum – inguinal adenitis with abscess formation; sign of the groove – groin fold dividing the swollen lymph nodes Int J Dermatol 15:26–33, 1976

Bed bug bites (Cimex lectularius) NEJM 359:1047, 2008

Molluscum contagiosum – in AIDS Clin Dermatol 38:160–175, 2020

Beetles – whiplash dermatitis; linear blisters JAAD 22:815–819, 1990; coconut beetles

Mycobacterium tuberculosis – lupus vulgaris – vegetative linear serpiginous lesion of neck Ped Derm 36:955–957, 2019; sporotrichoid pattern Int J Derm 40:336–339, 2001

Blister beetle dermatosis (Lytta vesicatoria) Ped Derm 9:246–250, 1992; JAAD 22:815–819, 1990; rove beetles (Paederus species) Cutis 69:277–279, 2002; AD 94:175–185, 1966 Botryomycosis Cutis 56:158–160, 1995 Box jellyfish (Cubozoa) (Chironex fleckeri) – linear plaques JAAD 61:733–750, 2009 Calipito itch – caterpillar dermatitis Candidiasis – erosio interdigitalis blastomycetica; median rhomboid glossitis Chikungunya fever – flagellate pigmentation Ped Derm 35:408–409, 2018 Coelenterate envenomation – acute jellyfish stings (cnidarian envenomation); recurrent eruptions following coelenterate envenomation The Clinical Management of Itching; Parthenon Publishing, 2000; p. xiii; JAAD 17:86–92, 1987; Portuguese man-of-war stings J Emerg Med 10:71–77, 1992

Myiasis, migratory; linear and serpiginous patches; Gasterophilus intestinalis, Hypoderma spp. JAAD 58:907–926, 2008 Nodular lymphangitis – M. marinum, Sporothrix, Leishmania braziliensis, Nocardia spp., M. chelonae, Francisella tularensis, Staphylococcus aureus Clin Inf Dis 21:433–434, 1995 Paederus beetle (rove beetle) dermatitis – linear papular, vesicular, and pustular dermatitis JAAD 57:297–300, 2007; Cutis 69:277–279, 2002; linear neutrophilic dermatitis Cutis 91:300–304, 2014 Papular urticaria Phaeohyphomycosis – linear vegetative plaques of legs; Coniothyrium Cutis 73:127–130, 2004 Scabies – linear burrows Scarlet fever – Pastia's lines (linear petechial streaks of the flexures) JAAD 39:383–398, 1998, Clin Inf Dis 14:2–13, 1992 Snake bite fang marks

Coccidioidomycosis JAAD 21:1138–1141, 1989

Sparganosis – linear migratory erythema with or without pustules

Coxsackie A 16 – linear erosions

Sporotrichosis – healed – linear scars

Coxsackie B4 – linear purpura of the ankles

Staphylococcal scalded skin syndrome

Cutaneous larva migrans; including oral irregular linear lesions Oral Surg 77:362–367, 1994

Streptococcal infection – linear crusts of Group B Streptococcus infection of the penis JAAD 20:367–390, 1989

Echovirus 6 Am J Dis Child 133:283, 1979

Strongyloidiasis, hyperinfection – migratory, linear, serpiginous papules and plaques; aseptic meningitis JAAD 70:113–1134, 2014

Eczema herpeticum Gnathostomiasis Gypsy moth caterpillar dermatitis JAAD 24:979–981, 1991 Hand, foot, and mouth disease

Syphilis – tertiary – linear scars; perioral rhagades; congenital – linear scar Actas Dermosifiliogr 56:203–206, 1965 (Spanish); corona veneris of secondary syphilis – linear papules along the hairline JAAD 55:187–189, 2006 Tinea corporis in HIV disease

Linear Lesions Tinea versicolor Tularemia – linear axillary ulcer with surrounding erythema with lymphocytic meningitis Clin Inf Dis 48:1266–1267,1327–1328, 2009 Unilateral laterothoracic exanthema (asymmetric periflexural exanthem of childhood Ped Derm 25:633–634, 2008; AD 138:1371– 1376, 2002; JAAD 29:799–800, 1993; JAAD 27:693–696, 1992 Varicella, congenital – linear erosions; linear array of scars – intrauterine varicella JAAD 43:864–866, 2000; AJDC 117:231–235, 1969 Verrucae, including flat warts (Koebnerized), cutaneous horn due to warts Yaws – secondary (crab yaws) – linear fissures of hyperkeratotic plantar surfaces

INFILTRATIVE DISEASES Alopecia mucinosa Amyloidosis – primary systemic; infiltration of nerves; chronic diffuse amyloidosis with nerve infiltration; lichen amyloid; beta-2 microglobulin amyloidosis – shoulder pain, carpal tunnel syndrome, flexor tendon deposits of hands, lichenoid papules, hyperpigmentation, subcutaneous nodules (amyloidomas) Int J Exp Clin Inves 4:187– 211, 1997; beta-2 microglobulin amyloidosis associated with hemodialysis – giant linear tumors of back JAMADerm 151:564– 565, 2015

Eosinophilic fasciitis – linear groove sign JAMADerm 156:582, 2020; Cutis 96:43–44, 2015 Erythema multiforme JAAD 57:690–699, 2007; Acta DV 35:318– 326, 1955 Hidradenitis suppurativa Interstitial granulomatous dermatitis (interstitial granulomatous dermatitis with plaques, linear rheumatoid nodule, railway track dermatitis, linear granuloma annulare, palisaded neutrophilic granulomatous dermatitis) – tender red, linear, curvilinear, serpiginous plaques with arthritis; annular plaques, papules, linear erythematous cords (rope sign), urticarial lesions JAMA Derm 149:609–614, 2013; JAAD 61:711–714, 2009; JAAD 47:319–320, 2002; JAAD 47:251–257, 2002; JAAD 46:892–899, 2002; JAAD 45:286–291, 2001; JAAD 34:957–961, 1996; Dermatopathol Prac Concept 1:3–6, 1995 Lymphangitis due to liquid nitrogen, dyshidrosis, cellulitis Median rhomboid glossitis Plasma cell panniculitis JAAD 21:357–360, 1989 Post-phlebitic linear hypertrichosis AD 124:30, 1988 Pruritic linear urticarial rash, fever, and systemic inflammatory disease of adolescents – urticaria, linear lesions, periorbital edema and erythema, and arthralgia Ped Derm 21:580–588, 2004 Sarcoid – in scars; subcutaneous sarcoid (Darier-Roussy sarcoid) – linear bands of forearms JAMADerm 149:1097–1098, 2013; BJD 153:790–794, 2005

Intralymphatic histiocytosis JAMADerm 155:960–961, 2019

Sclerosing lipogranuloma – personal observation

Cutaneous mucinosis of infancy – congenital linear variant of self-­healing juvenile cutaneous mucinosis AD 122:790, 1986; AD 119:272–273, 1983

Superficial vegetating pyoderma

Juvenile xanthogranuloma Ped Derm 21:513–515, 2004

METABOLIC

Reactive intravascular histiocytosis – black necrotic eschar of scrotum and gluteal cleft; associated with tonsillitis BJD 154:560– 563, 2006

Acrodermatitis enteropathica or acquired zinc deficiency – linear bullae in palmar creases

Rosai-Dorfman disease Am J Dermatopathol 39:776–781, 2017 Scleromyxedema – linear papules with skin thickening AD 148:1317–1322, 2012; leonine facies, arthritis and rash, sclerodermoid changes JAAD 44:273–281, 2001 Self-healing juvenile cutaneous mucinosis – red nodules of the face, scalp, hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; JAAD 44:273–281, 2001; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973 Urticaria pigmentosa (mastocytosis) – Darier’s sign

INFLAMMATORY DISEASES Anetoderma following angular cheilitis BJD 138:923–924, 1998 Angular cheilitis – linear fissures; candida, staphylococci, immune deficiency, dentures, overbite, atopic dermatitis, riboflavin, iron, folate deficiencies, protein malnutrition, hypersalivation (drooling) (Down’s syndrome), edentulous patients, prognathism Connective tissue panniculitis – nodules, atrophic linear plaques of the face, upper trunk, or extremities AD 116:291–294, 1980 Crohn's disease – linear oral ulcers in buccal sulcus JAAD 36:697–704, 1997; vulvar linear knife-cut ulcers Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 162; perianal vegetative linear plaque Ped Derm 23:49–52,2006

587

Acromegaly – cutis verticis gyrata, linear furrowing of facial lines Addison’s disease – hyperpigmentation of palmar creases Ped Derm 25:215–218, 2008 Calcinosis cutis – iatrogenic metastatic calcinosis cutis Ped Derm 20:225–228, 2003; plate-like calcinosis cutis BJD 150:753–756, 2004 Cholinergic dermatographism – red line with punctate wheals BJD 115:371–177, 1986 Cushing's disease – striae Diabetes mellitus – diabetic dermopathy; sometimes linear atrophic brown scars Cutis 3:955–958, 1967 Diagonal ear lobe crease Cutis 23:328–331, 1979; NEJM 289:327– 328, 1973 Intrahepatic cholestasis of pregnancy – linear excoriations AD 143:757–762, 2007 Necrobiosis lipoidica diabeticorum – linear array Koebnerizing around a scar Cutis 67:158–160, 2001 Obesity – striae Panhypopituitarism – fine wrinkling around eyes and mouth Porphyrias – erythropoietic porphyria – linear and pitted scars Eur J Pediatr 159:719–725, 2000; J Inherit Metab Dis 20:258–269, 1997; BJD 131:751–766, 1994; Curr Probl Dermatol 20:123–134, 1991; Am J Med 60:8–22, 1976; hereditary coproporphyria; acute intermittent porphyria – linear abdominal scars Pregnancy – hyperpigmentation of linea nigra; pigmentary demarcation lines of pregnancy JAAD 11:438–440, 1984

588 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Primary osteoma cutis – generalized osteomas; unilateral anodontia, hemihypertrophy, linear basal cell nevus Pruritic urticarial papules and plaques of pregnancy – lesions localized in abdominal striae JAAD 39:933–939, 1998; JAAD 10:473–480, 1984; Clin Exp Dermatol 7:65–73, 1982; JAMA 241:1696–1699, 1979 Verruciform xanthoma, disseminated BJD 151:717–719, 2004 Vitamin B12 deficiency – linear erosions of lateral or dorsal tongue; linear erosions of hard and soft palate JAAD 60:498–500, 2009 Xanthomas – eruptive xanthomas (koebnerized) J Dermatol 19:48–50, 1992; JAAD 19:95–111, 1988; plane xanthomas; tendinous xanthomas – personal observation

NEOPLASTIC Acantholytic dyskeratotic epidermal nevus J Eur Acad /Dermatol Venereol 17:196–199, 2003; BJD 138:875–878, 1998 Achromic nevus Acquired periungual fibrokeratoma – linear fleshy nodule emanating from proximal nail fold overlying nail Dermatol Clin 33:243–255, 2015; JAMADerm 150:456–457, 2014 Actinic keratosis with cutaneous horn Angiolipomas Angiosarcoma – linear red plaque of scalp JAAD 62:538–539, 2010 Basal cell carcinoma Cutis 104:114–116, 2019; J Eur Acad Derm Ven 31:E359–362 2017; Clin Exp Dermatol 36:231–234, 2011; Open Ophthalmol J 1:20–22, 2007; J Plast Reconstr Aesthet Surg 59:419–423, 2006; Dermatol Surg 25:63–67, 1999; Tex Med 93:57–59, 1997; Cutis 51:287–289, 1993; Int J Dermatol 24:124– 125, 1985; giant linear Int J Dermatol 33:284, 1994 linear black macule Cutis 97:384,406–407, 2016 Basal cell nevus (linear basal cell nevus) – resemble comedones; usually linear translucent telangiectatic papules, may ulcerate; macular hypopigmentation, alopecia, cysts, striae Cutis 78:122– 124, 2006; Cutis 46:493–494, 1990; AD 114:95–97, 1978; BJD 74:20–23, 1962; Arch Dermatol Syphilol 65:471–476, 1952 Basaloid follicular hamartoma AD 133:381–386, 1997; JAAD 27:316–319, 1992; congenital systematized basaloid follicular hamartoma with microphthalmia and hemimegalencephaly; unilateral linear hypopigmented macules and streaks Ped Derm 28:555–560, 2011 Basaloid squamous cell carcinoma of the skin – ulcerated plaque of inguinal crease; necrotic linear ulcer of inguinal crease JAAD 64:144–151, 2011 Becker's nevus Cutis 75:122–124, 2005 Blue nevi JAAD 36:268–269, 1997 Clear cell papulosis – white macules in the milk line Am J Surg Pathol 11:827–834, 1987 Connective tissue nevus mimicking epidermal nevus JAAD 67:233–239, 2012; JAAD 16:264–266, 1987; papulolinear collagenoma JAAD 54:S240, 2006; JAAD, 50:797–798, 2004; arborizing linear collagenoma Ped Derm 26:111–112, 2009; linear collagenoma of the neck Ped Derm 26:626–628, 2009

Dermatofibroma – congenital multiple clustered dermatofibroma – red plaque and papules BJD 142:1040–1043, 2000; Ann DV 111:163–164, 1984 Dermatomyofibroma – linear hyperpigmented plaque Ped Derm 16:456–459, 1999 Eccrine angiomatous hamartoma – vascular nodule; macule, red plaque, acral nodule of infants or neonates; painful, red, purple, blue, yellow, brown, skin-colored on extremities, trunk, buttocks, neck Ped Derm 23:365–368, 2006 Eccrine nevi – linear eccrine nevi include:   Eccrine poromas AD 112;841, 1976  Eccrine spiradenoma AD 84:792, 1961; zosteriform Dermatol Online J Aug 2017   Eccrine syringofibroadenoma   Linear eccrine nevus – flesh colored to brown  Syringomas  Porokeratotic eccrine ostial and dermal duct nevus (palms and soles; verrucous papules) Eccrine nevus – pigmented patch, depressed nodule, and/or linear papules JAAD 51:301–304, 2004; Acta DV (Stockh)82:154–156, 2002; AD 117:357–359, 1981; with comedones AD 117:357–359, 1981 Eccrine poroma – linear and zosteriform AD 112:841–844, 1976 Eccrine spiradenomas – AD 138:973–978, 2002; linear with eyelid involvement J Eur Acad Dermatol Venereol 15:163–166, 2000; Plast Reconstr Surg 68:100–102, 1981; JAAD 2:59–61, 1980 Eccrine syringofibroadenoma JAAD 36:569–576, 1997; AD 933–934, 1994; AD 126:945–949, 1990; reactive peristomal eccrine syringofibroadenoma – cerebriform verrucous plaque JAAD 58:691–696, 2008 Ectopic meningothelial hamartoma – white linear plaque of occipital scalp; congenital red plaque becomes orange-yellow then white Ped Derm 34:99–100, 2017; Ped Derm 31:208–211, 2014; Ped Derm 28:677–680, 2011; Am J Surg Pathol 14:1–11, 1980 Epidermal nevus JAAD 20:476–478, 1989; Dermatologica 166:84, 1983; epidermal nevus with scattered open comedones; HaileyHailey-like; lichenoid epidermal nevus JAAD 20:913–915, 1989; epidermal nevus of scrotum Ped Derm 24:447–448, 2007 Eruptive lipomas, focal myositis with bilateral painful nodules Cutis 54:189, 1994 Follicular cysts, nevoid array – personal observation Giant cell tumor of the tendon sheath Granular cell myoblastoma of the lip AD 121:1197–1202, 1985, Cancer 25:415–422, 1970 Hamartoma moniliformis (hair follicle hamartoma) – linear array of skin-colored papules of the face and neck BJD 143:1103–1105, 2000; AD 101:191–205, 1970; linear hair follicle nevi Dermatology 206:172–174, 2003 Inflammatory linear verrucous epidermal nevus (ILVEN) – linear dermatitic and/or psoriasiform plaques; often on leg AD 113:767– 769, 1977; AD 104:385–389, 1971 Infantile myofibromatosis Ped Derm 5:37–46, 1988 Kaposi's sarcoma – in AIDS AD 124:327–329, 1988 Keloid

Cylindromas JAAD 26:821–824, 1992

Keratoacanthomas – multiple keratoacanthomas of Grzybowski

Deep penetrating nevus – linear AD 139:1608–1610, 2003; nonlinear deep penetrating nevus – black, blue, brown, gray, or darkly pigmented nevus of the head, neck, and scalp JAAD 71:1234–1240, 2014

Leiomyomas JAAD 46:477–490, 2002 Leukemia – congenital monocytic leukemia with disseminated linear calcinosis cutis in resolved cutaneous lesions BJD 150:753–756,

Linear Lesions

589

2004; leukemia cutis in linear scar AD 123:88–90, 1987; zosteriform leukemia cutis

43:364–367, 2000; JAAD 24:300–301, 1991; Cutis 46:495–497, 1990

Leukoplakia – HPV-associated sublingual leukoplakia BJD 158:644–646, 2008

Linear rhabdomyomatous mesenchymal hamartoma – unilateral facial depressions, atrophy, and hyperpigmentation of the chin Ped Derm 36:716–717, 2019

Nevus depigmentosus JAAD 55:423–428, 2006 Lymphoma – cutaneous T-cell lymphoma with fissured palms; adult T-cell leukemia/lymphoma with cutis verticis gyrata BJD 155:617– 620, 2006; B-cell lymphoma – groove sign – personal observation; anaplastic large cell lymphoma Am J Dermatopathol 39:863–866, 2017 Lymphoplasmacytic plaque – linear papules Ped Derm 36:365–367, 2019 Melanoma in situ Cureus 9:e1696, 2017 Metastases – cutaneous squamous cell carcinoma Dermatol Online J 19:18174, 2013; zosteriform lung cancer Respirol Case Rep 18:e00515, 2019; zosteriform cutaneous metastases – breast, colon Clin Exp Dermatol 43:734–736, 2018

Sebaceous hyperplasia, congenital Ped Derm 24:443–445, 2007; JAAD 48:149–150, 2003; Am J Dermatopathol 6:237–243, 1984; juxtaclavicular beaded lines Dermatology 200:283, 2000; Dermatology 197:94–95, 1998; J Cutan Pathol 18:464–468, 1991; prepubescent sebaceous hyperplasias – linear neck papules Ped Derm 28:198–200, 2011 Sebaceous hyperplasia hamartoma – personal observation Seborrheic keratoses – associated with underlying malignancy JAAD 18:1316–1321, 1988 Smooth muscle hamartoma – linear, follicular spotted appearance BJD 142:138–142, 2000; AD 114:104–106, 1978; linear atrophic plaque Ped Derm 13:222–225, 1996

Mucinous nevus (connective tissue nevus of the proteoglycan type) – linear pink papules of chest JAMADerm 150:1018–1019, 2014; BJD 148:1064–1066, 2003; JAAD 37:312–313, 1997; AD 132:1522–1523, 1996; BJD 1331:368–370, 1994

Spiradenomas, multiple Plast Reconstr Surg 68:100–102, 1981

Multiple deep penetrating nevi AD 139:1608–1610, 2003

Straight hair nevus Int J Derm 9:47–49, 1970

Neurilemmomas – linear array on forehead Clin Exp Dermatol 16:247–249, 1991

Stucco keratoses

Neuromas – linear with striated pigmentation J Cutan Pathol 14:43–48, 1987 Nevoid basal cell carcinoma syndrome; may be with comedones Dermatol 200:299–302, 2000; JAAD 20:973–978, 1989; JAAD 15:1023–1030, 1986; BJD 113:365, 1985; AD 100:187–190, 1969; BJD 74:20–23, 1962; Arch Dermatol Syphilol 65:471, 1952; Nevoid basal cell carcinoma syndrome with type II mosaicism – Blaschkoesque atrophy, Blaschko-­esque pits of palms; linear papules of foot; white papules and plaques; segmental hyper- and hypopigmented patches BJD 169:1342–1345, 2013 Nevus comedonicus Ped Derm 32:216–219, 2015; J Cutan Pathol 31:502–505, 2004; AD 116:1048–1050, 1980; Trans St John’s Hosp Dermatol Soc Lond 59:45–51, 1973; AD 97:533–535, 1968 Nevus lipomatosis J Derm Surg Onc 9:279–281, 1983; Int J Derm 14:273–276, 1975 Nevus sebaceous – JAAD 61:563–571, 2009; Arch Dermatol Syphilol 33:355–394, 1895; linear nevus sebaceous syndrome (Schimmelpenning-Feuerstein-Mims syndrome) JAAD 61:563–578, 2009; Fortschr Geb Rontgenstr Nuklearmed 87:716–720, 1957 Porokeratosis – linear porokeratosis Cutis 81:479–483, 2008; Ped Derm 21:682–683, 2004; AD 135:1544–1555,1547–1548, 1999; Ped Derm 4:209, 1987; AD 109:526–528, 1974; unilateral punctate porokeratosis; porokeratosis of Mibelli Porokeratotic adnexal ostial nevus (conifying porokeratotic eccrine ostial and dermal duct nevus with porokeratotic eccrine and hair follicle nevus – linear, hyperkeratotic, filiform lesions with comedones; presents as red patch with red and atrophic linear and curvilinear erosions; unilateral breast hypoplasia and multifocal squamous cell carcinomas JAMA Derm 149:869–870, 2013; JAAD 61:1060–1069, 2009; BJD 103:435–441, 1980; BJD 101:717–722, 1979 Porokeratotic eccrine ostial and dermal duct nevus – mutation in GJB2 JAMADerm 151:638–641, 2015; seen in KID syndrome Ped Derm 27:514–517, 2010; resemble nevus comedonicus; linear keratotic papules with central plugged pit; may be verrucous; filiform; anhidrotic or hyperhidrotic; most common on palms and soles JAAD

Spitz nevi Ann DV 118:345–347, 1988 Squamous cell carcinoma with perineural invasion; linear Cureus 9;e1696, 2017

Syringocystadenoma papilliferum – linear red papules JAAD 45:139–141, 2001; AD 121:1197–1202, 1985; linear verrucous papules Indian J Dermatol Vnereol Leprol 75:318–319, 2009; Acta DV 88:528–529, 2008; AD 138:1091–1096, 2002; linear vascular appearing nodules of the neck AD 144:1509–1514, 2008; giant multilobulated linear tumor Ped Derm 26:758–759, 2009; linear multilobulated verrucous plaque Ped Derm 28:61–62, 2011 Syringoma – unilateral linear J Dermatol 23:505–506, 1996; JAAD 4:412–416, 1981 Trichilemmal cysts – with segmental multiple glomus tumors Dermatology 200:75–77, 2000; in an extensive comedo nevus BJD 96:545–548, 1977 Trichoadenoma of forehead – linear yellow verrucous L-shaped plaque JAAD 57:905–906, 2007 Trichodiscomas Ann Derm Vener 108:837, 1981 Trichoepitheliomas JAAD 37:881–883, 1997; JAAD 14:927–930, 1986 Waldenstrom’s macroglobulinemia with neoplastic cellular infiltrate – deck chair sign JAAD 52:S45–47, 2005

PARANEOPLASTIC DISEASES Diffuse normolipemic plane xanthoma JAAD 35:819–822, 1996 Necrobiotic xanthogranuloma with paraproteinemia – yellow linear plaques within scars Int J Derm 43:293–295, 2004(burn scar); Orbit 27:191–194, 2008; Mayo Clin Proc 72:1028–1033, 1997; AD 128:94–100, 1992(surgical scars)

PHOTODERMATOSES Actinic prurigo JAAD 44:952–956, 2001; Australas J Dermatol 42:192–195, 2001; Photodermatol Photoimmunol Photomed 15:183–187, 1999; Int J Dermatol 34:380–384, 1995; JAAD 26:683–692, 1992; JAAD 5:183–190, 1981; Clin Exp Dermatol 2:365–372, 1977; familial, in North American Indians Int J Dermatol 10:107–114, 1971; in Caucasians BJD 144:194–196, 2001;

590

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

polymorphic light eruption of American Indians; occurrence in non-Indians JAAD 34:612–617, 1996; Southeast Asian Photodermatol Photoimmunol Photomed 9:225–228, 1992

Cutis verticis gyrata AD 125:434–435, 1989

Berloque dermatitis

Dermatofibrosis lenticularis disseminata

Dermatoheliosis (solar elastosis) (sun damage – basophilic alteration of collagen) – linear wrinkling of face

Dermatographism – personal observation

Keratoelastoidosis marginalis (degenerative collagenous plaques of the hands) – linear translucent papules of radial hand and first web space JAAD 51:1–21, 2004; AD 82:362–366, 1960 Phytophotodermatitis – rue (Ruta graveolens) Dermatitis 18:52–55, 2007; linear and bullous lesions Rook p. 790, 1998, Sixth Edition; meadow dermatitis (Umbelliferae); lemon, lime, celery, parsnip, figs, carrots, dill, parsley, meadowgrass, giant hogweed, wheat, clover, cocklebar, buttercup, shepherd’s purse, pigweed JAAD 67:1093– 1110, 2012 Solar elastotic bands (nodules) of forearm JAAD 15:650–656, 1986 Stellate and discoid pseudoscars – linear scars AD 105:551–554, 1972

PRIMARY CUTANEOUS DISEASES Acquired linear dermal melanocytosis AD 118:125–128, 1982   Differential diagnosis of linear hyperpigmented lesions:    Cafe au lait macule    Dermal melanocyte hamartoma   Epidermal nevus    Hyperpigmentation overlying plexiform neurofibroma    Linear blue nevus    "Nevoid" macular amyloidosis    Nevus of Ito or Ota   Nevus spilus   Post-inflammatory hyperpigmentation    Progressive cribriform and zosteriform hyperpigmentation    Progressive zosteriform macular pigmented lesions    Zosteriform lentiginous nevus

Darier's disease – linear Darier’s disease; linear pink papules AD 143:535–540, 2007; BJD 105:207–214, 1981

Digitate dermatosis – personal observation Dupuytren’s contracture Elastosis perforans serpiginosa Hautarzt 43:640–644, 1992; AD 97:381–393, 1968 Epidermolysis bullosa – dominant dystrophic – personal observation Epidermolysis bullosa pruriginosa (DDEB) – dominant dystrophic – linear prurigo; linear pruriginous or lichenified plaques Ped Derm 32:549–550, 2015; AD 147:956–960, 2011; BJD 152:1332–1334, 2005; BJD 129:443–446, 1993; linear lesions and violaceous hypertrophic linear scars Ped Derm 29:725–731, 2012; JAAD 56:S77–81, 2007; BJD 146:267–274, 2002; mild acral blistering at birth or early childhood; violaceous papular and nodular lesions in linear array on shins, forearms, trunk; lichenified hypertrophic and verrucous plaques in adults BJD 130:617–625, 1994; neonatal EB Clin Exp Dermatol 44:62–65, 2019 Epidermolytic palmoplantar keratoderma, woolly hair, and dilated cardiomyopathy – striated palmoplantar keratoderma, follicular keratosis, clubbing, vesicles and bullae on trunk, psoriasiform keratoses on knees, legs, and feet JAAD 39:418–421, 1998 Erythema elevatum diutinum – personal observation Flegel's disease Focal linear elastosis – personal observation Follicular atrophodermas – linear scars; Conradi's syndrome, Bazex syndrome, palmoplantar keratoderma with follicular keratoses and palmoplantar hypohidrosis Futcher’s (Voigt’s) lines – lines of demarcation at anterolateral upper arms and posteromedial lower limbs Cutis 92:100–101, 2013; Cutis 32:376–377, 1983; Science 88:570–571, 1938

Acquired perforating collagenosis AD 143:1201–1206, 2007

Granuloma annulare JAAD 21:1138–1141, 1989; linear in scar JAAD 50:S34–37, 2004

Acrokeratoelastoidosis AD 127:113–118, 1991

Hailey-Hailey disease BJD 112:349–355, 1985

Ashy dermatosis (erythema dyschromicum perstans)

Harlequin ichthyosis – linear fissures JAAD 58:653–656, 2008

Atopic dermatitis – hyperlinear palms Ped Derm 36:213–218, 2019; BJD 167:1165–1169, 2012; Dennie-Morgan folds JAAD 57:690– 699, 2007; BJD 131:134–135, 1994

Ichthyosis hystrix

Atrophia maculosa varioliformis cutis – linear scars Ped Derm 18:230–233, 2001; JAAD 21:309, 1989; BJD 115:105–109, 1986 Atrophoderma of Pasini and Pierini – linear scars Atrophy linearis semicircularis (lipoatrophia semicircularis) JAAD 39:879–881, 1998 Axillary granular parakeratosis JAAD 59:177–178, 2008; Cutis 80:55–56, 2007 Blaschkitis Eur J Dermatol 29:281–286, 2019; J Cut Pathol 41:950–954, 2014 Bullous congenital ichthyosiform erythroderma – personal observation Circumscribed acral (palmar) hypokeratosis – atrophic pink patches and plaques of palms JAAD 57:285–291, 2007 Confluent and reticulated papillomatosis – linear pseudo-striae Actas Dermosifiliogr 109:e7–11, 2018 Cutis laxa – acquired cutis laxa of the face; linear furrows Ped Derm 28:421–423, 2011

Ichthyosis vulgaris – hyperlinear palms BJD 161:139–145, 2009; Infantile granular parakeratosis JAAD 50:S93–96, 2004 Juxtaclavicular beaded lines Keratosis lichenoides chronica (Nekam’s disease) – reticulated flat-­topped keratotic papules, linear arrays, atrophy, comedo-like lesions, prominent telangiectasia; conjunctival injection, seborrheic dermatitis-­like eruption; acral dermatitis over toes; punctate keratotic papules of palmar creases Cutis 86:245–248, 2010; Ped Derm 26:615–616, 2009; AD 145:867–69, 2009; AD 144:405–410, 2008;JAAD 49:511–513, 2003; Dermatology 201:261–264, 2000; JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; AD 131:609– 614, 1995; AD 105:739–743, 1972; Presse Med 51:1000–1003, 1938; Arch Dermatol Syph (Berlin) 31:1–32, 1895; in children JAAD 56:S1–5, 2007 Leukoedema Community Dent Oral Epidemiol 9:142–146, 1981; AD 116:906–908, 1980 Lichen nitidus Ann DV 116:814–815, 1989 Lichen planus – along Wallace’s line AD 137:85–90, 2001; BJD 142:836–837, 2000; JAAD 20:913–915, 1989; lichen planopilaris of

Linear Lesions the face JAAD 38:633–635, 1998; JAAD 21:131–132, 1989; in striae; linear lichen planopilaris Cutis 92:303–305, 2013 Lichen planus pigmentosus J Korean Med Sci 19:152–154, 2004; lichen planus pigmentosus inversus – linear gray-brown macules of intertriginous areas in folds of the chest, abdomen, and groin AD 147:1097–1102, 2011 Lichen ruber moniliformis

591

  vs. nevus corniculatus    Paraneoplastic hyperkeratosis of palms and soles    Pityriasis rubra pilaris Steatocystoma multiplex, congenital linear lesions of the nose Ped Derm 17:136–138, 2000 Striae distensae (striae atrophicans)

Lichen sclerosus et atrophicus Eur J Dermatol 8:575–577, 1998

Striate palmoplantar keratoderma (Brunauer-Fohs-Siemens) Int J Dermatol 40:644–645, 2001; Cutis 61:21–214, 1998

Lichen simplex chronicus

Striped hyperpigmentation of the torso

Lichen striatus Eur J Dermatol 10:536–539, 2000; cutaneous lesions and linear nail notch JAAD 36:908–913, 1997

Terra firme Cutis 101:205–206, 2018

Linea alba – buccal mucosa Linear nevoid hypertrichosis Ped Derm 25:120–122, 2008 Linea nigra Linear and whorled nevoid hypermelanosis Linear bands in infancy – acquired horizontal raise linear bands of legs and ankles Ped Derm 24:391–393, 2007; Ped Derm 20:346– 349, 2005; BJD 149:436–437, 2003; BJD 147:359–363, 2002 Linear focal elastosis – yellow linear bands on lower back of elderly men JAAD 47:S189–192, 2002; BJD 145:188–190, 2001; JAAD 36:301–303, 1997; AD 131:1069–1074, 1995; JAAD 20:633–636, 1989 Melasma Cutis 61:229–232, 1998 Milia en plaque JAAD 31:107, 1994 Papuloerythroderma of Ofuji – deck chair sign Pigmentary demarcation lines groups C and E – hypopigmented; hyperpigmented Pigmentary lines of the newborn – resolves without treatment JAAD 28:893–894, 1993 Pityriasis lichenoides et varioliformis acuta – linear scars Pityriasis rosea – linear scars in bullous pityriasis rosea Pseudo-acanthosis nigricans Psoriasis – linear psoriasis JAAD 57:690–699, 2007; JAAD 30:130–133, 1994; Koebner phenomenon Berlin Klin Wochenschr 21:631–632, 1878; psoriasis in scars, scalp psoriasis; linear pustular psoriasis JAAD 57:690–699, 2007; JAAD 39: 635–637, 1998; blaschko Clin Exp Dermatol 41:775–778, 2016 Pterygium colli medianum Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.58–59

Transient infantile patterned hyperpigmentation Ped Derm 29:372– 373, 2012 Transverse nasal groove – with milia; embryonic fault line AD 148:1037–1039, 2012; AD 84:316–317, 1961; AD 63:70–72, 1951 Unna-Thost palmoplantar keratoderma – diffuse non-epidermolytic palmoplantar keratoderma – autosomal dominant; Wallace’s line well demarcated; mutations in keratin 16 Hum Mol Genet 4:1875– 1881, 1995; mutation in keratin 1 JID 103:764–769, 1994 Vermiculate atrophoderma (keratosis pilaris atrophicans) – linear scars Vitiligo – segmental vitiligo; Koebner phenomenon BJD 167:1017– 1024, 2012 Vohwinkel's syndrome (keratoderma hereditaria mutilans) – autosomal dominant; honeycomb palms, starfish keratoses JAAD 44:376–378, 2001 Vorner's palmoplantar keratoderma – linear erosions in infancy Wallace's lines BJD 114:513–514, 1986

PSYCHOCUTANEOUS DISEASES Factitial dermatitis – linear lesions, ulcers, and linear scars JAAD 76:779–791, 2017; JAAD 1:391–407, 1979; self-induced linear purpura of arms Arch Pediatr 24:45–51, 2017; linear bullae due to deodorant spray Ped Derm 37:559–560, 2020 Hematohidrosis – linear dripping blood-tinged discharge from eyes, ears, axilla, mouth, rectum, vagina, urethra, scalp, neck, trunk, extremities Indian J Dermatol 58:478–480, 2013; Indian Pediatr 50, 2013; Am J Clin Dermatol 11:440–443, 2010; Am J Dermatopathol 30:135–139, 2008; Ophthalmic Plastic Reconstr Surg 20:442–447, 2004

Railway track-like dermatitis of the anterior axillary fold JAAD 20:920–923, 1989

Neurotic excoriations Am Fam Phys 64:1981–1984, 2001

Raised limb bands (raised linear bands of infancy) – curvilinear bands of extremities Ped Derm 27:312–313, 2010; BJD 149:436– 437, 2003; BJD 147:359–363, 2002

Skin picking – linear hypopigmented scars JAAD 76:779–791, 2017

Raphe mediana supraumbilicus Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.58–59

SYNDROMES

Reactive perforating collagenosis AD 143:1201–1206, 2007; JAAD 10:561–568, 1984 Relapsing linear acantholytic dermatosis JAAD 33:920–922, 1995; BJD 112:349–355, 1985; linear acantholytic dermatosis

Self-mutilation

Aarskog syndrome – single palmar crease J Pediatr 77:856–861, 1970 Adams-Oliver syndrome – personal observation Acrocephalopolysyndactyly – linear submental scars Alagille syndrome – linear palmar xanthomas

Scalp hair heterochromia, linear Ped Derm 31:733–734, 2014

Anhidrotic ectodermal dysplasia – linear atrophic lesions of face

Sclerotic panatrophy – may follow morphea or occur spontaneously; linear or annular or circumferential bands around limbs

Ataxia telangiectasia – linear telangiectasias Ann Int Med 99:367– 379, 1983

Sock line hyperpigmentation (may be same as congenital curvilinear palpable hyperpigmentation) AD 143:428–430, 2007; JAAD 53:S162–164, 2005

Auriculotemporal syndrome (Frey syndrome) – linear flush and/or sweating on cheek after eating Ped Derm 17:415–416, 2000; AD 133:1143–1145, 1997

Spiny hyperkeratosis JAAD 31:157–190, 1994

Bannayan-Riley-Ruvalcaba-Zonana syndrome (PTEN phosphatase and tensin homolog hamartoma) – transverse palmar crease,

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

dolichocephaly, frontal bossing, macrocephaly, ocular hypertelorism, long philtrum, thin upper lip, broad mouth, relative micrognathia, lipomas, penile or vulvar lentigines, facial verruca-like or acanthosis nigricans-like papules, multiple acrochordons, angiokeratomas, accessory nipple, syndactyly, brachydactyly, vascular malformations, arteriovenous malformations, lymphangiokeratoma, goiter, hamartomatous intestinal polyposis JAAD 53:639–643, 2005 Beckwith-Wiedemann syndrome (Exomphalos-MacroglossiaGigantism) (EMG) syndrome – autosomal dominant; hemihypertrophy, polydactyly, linear earlobe grooves, zosteriform rash at birth, exomphalos, macroglossia, visceromegaly, facial salmon patch of forehead, upper eyelids, nose, and upper lip and gigantism; circular depressions of helices (posterior helical ear pit); increased risk of Wilms’ tumor, adrenal carcinoma, neuroblastoma, hepatoblastoma, and rhabdomyosarcoma BJD 164:245–256, 2011; JAAD 37:523– 549, 1997; Am J Dis Child 122:515–519, 1971 Blau or Jabs syndrome (familial juvenile systemic granulomatosis) – autosomal dominant; translucent skin-colored papules (non-caseating granulomas) in linear arrays or as zebra stripes of trunk and extremities with uveitis, synovitis, arthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; camptodactyly (flexion contractures of PIP joints) mutations in NOD2(nucleotidebinding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) AD 143:386–391, 2007; Clin Exp Dermatol 21:445–448, 1996 Branchio-oculo-facial syndrome (dermal thymus resembling linear scar) – autosomal dominant Ped Derm 12:24–27, 1995; AD 125:1681–1684, 1989; Am J Med Genet 27:943–951, 1987 Brooke-Spiegler syndrome – linear papular eruption of eccrine spiradenomas Australas J Dermatol 44:144–148, 2003 Cantu syndrome – linear deep plantar creases, congenital hypertrichosis, cardiomegaly, osteochondrodysplasia, coarse facial features Am J Med 92:191–194, 2000 Carbohydrate-deficient glycoprotein syndrome – emaciated appearance; lipoatrophy over buttocks; lipoatrophic streaks extend down legs; high nasal bridge, prominent jaw, large ears, inverted nipples, fat over suprapubic area and labia majora, fat pads over buttocks; hypotonia Cardiofaciocutaneous syndrome – linear earlobe creases; brittle, dark, sparse curly hair; increased numbers of melanocytic nevi; characteristic facies with thick facial appearance, broad nose, frontal bossing, ulerythema ophryogenes, sparse eyebrows; 1–2 café au lait macules; palmoplantar keratoderma; pulmonic stenosis, hypertrophic cardiomyopathy, congenital heart defects, psychomotor delay, failure to thrive; RASopathy (BRAF, MAP2K1, MAP2K2, KRAS mutations) BJD 164:521–529, 2011 Carpenter syndrome – single palmar crease Am J Med Genet 28:311–324, 1987 Carvajal syndrome – striate palmoplantar keratoderma with woolly hair and cardiomyopathy Cerebro-hepato-renal syndrome (Zellweger syndrome) – single palmar crease Am J Med Genet 22:419–426, 1985 CHILD syndrome – congenital hemidysplasia, ichthyosis, limb defects, ichthyosiform erythroderma with verruciform xanthoma, linear red waxy scaling eruptions, and hypopigmented bands; linear hyperkeratosis with brownish scaling of fingers and toes; linear demarcation of half-body psoriasiform dermatitis with hemidysplasia; mutation in NSDHL (NAD(P)H steroid dehydrogenase-like protein BJD 159:1204–1206, 2008; Ped Derm 15:360–366, 1998; AD 142:348–351, 2006; Ped Derm 15:360–366, 1998; xanthomatous pattern Dermatologica 180:263–266, 1990; AD 123:503–509, 1987

Chromosome deletion Xp22.1 – Gazali-Temple syndrome JAAD 31:680–682, 1994   vs. Adams-Oliver syndrome   Aicardi syndrome    Cutis marmorata telangiectatica congenita   Goltz’s syndrome Cohen syndrome – single palmar crease J Med Genet 17:430–432, 1980 Congenital hypertrophy of the retinal pigment epithelium – linear hyperpigmentation Am J Med Genet 126A:89–92, 2004 Congenital ichthyosiform dermatosis with linear keratotic flexural papules and sclerosing palmoplantar keratoderma AD 125:103– 106, 1989 Conradi-Hunermann syndrome (chondrodysplasia punctata – X-linked dominant) – linear and whorled hyperkeratosis, follicular atrophoderma of forearms in Blaschko distribution; linear atrophic lesions with follicular plugging of scalp; cicatricial alopecia of the scalp; patchy patterned alopecia, generalized xerosis; cataracts, chondrodysplasia punctata; asymmetric shortening of long bones epiphyseal stippling, short stature, short limbs, kyphoscoliosis, craniofacial abnormalities); short arms and legs; cataracts; X-linked; mutation in emopamil binding protein (EBP) Ped Derm 31:493–496, 2014; BJD 160:1335–1337, 2009; Curr Prob in Derm VII:143–198, 1995; AD 121:1064–1065, 1985; ichthyotic and psoriasiform lesions (Blaschko hyperkeratotic scaling), nail defects, cicatricial alopecia, follicular pitted scars, skeletal anomalies JAAD 33:356–360, 1995; Hum Genet 53:65–73, 1979; neonatal transient scaly plaques of limbs, trunk, and scalp; scaly rash disappears in months leaving hypo- or hyperpigmented streaks with follicular atrophoderma and patchy scarring alopecia; CDPX2 – X-linked lethal in males; X-linked dominant (mosaic for emopamil-binding protein); X-linked recessive – male EBP disorder with neurologic defects BJD 166:1309– 1313, 2012 Cornelia de Lange (Brachmann-de Lange) syndrome – single palmar crease, hypoplastic epidermal ridges of palms, soles, fingers, and toes; hypoplastic nipples and umbilicus, umbilical hernia Syndromes of the Head and Neck, p.303, 1990; hypoplastic genitalia, generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, posterior neck, and arms, low-set ears, arched palate, antimongoloid palpebrae; congenital eyelashes; xerosis, especially over hands and feet, nevi, facial cyanosis, lymphedema Ped Derm 24:421–423, 2007; JAAD 56:541–564, 2007; JAAD 48:161–179, 2003; Ped Derm 19:42–45, 2002; JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993; Am J Med Genet 20:453–459, 1985; in infancy, linear hyperkeratotic lesions BJD 160:1335–1337, 2009; BJD 157:1225–1229, 2007; linear hyperkeratotic bands with diffuse erythema and scale, follicular atrophoderma, hypochromic areas, scalp alopecia Ped Derm 15:299–303, 1998; AD 127:539–542, 1991; Hum Genet 53:65–73, 1979 Costello syndrome – linear papillomatous papules of upper lip BJD 168:903–904, 2013; failure to thrive; linear deep palmar creases Ped Derm 30:665–673, 2013; warty papules around nose and mouth, legs, perianal skin; coarse facial features, hypotonia, loose skin of the neck, hands, and feet; acanthosis nigricans; low-set protuberant ears, thick palmoplantar surfaces, gingival hyperplasia,

Linear Lesions hypoplastic nails, moderately short stature, craniofacial abnormalities, hyperextensible fingers, tight Achilles tendon, curly or fine sparse curly hair, perianal and vulvar papules, diffuse hyperpigmentation, generalized hypertrichosis, multiple nevi; rhabdomyosarcoma, neuroblastoma, transitional cell carcinoma of the bladder BJD 164:245–256, 2011; Ped Derm 20:447–450, 2003; JAAD 32:904–907, 1995; Am J Med Genet 47:176–183, 1993; Aust Paediat J 13:114–118, 1977 Craniodysostosis with extremity bands Delleman-Oorthuys syndrome Disorganization syndrome – filiform worm-like projections, syndactyly, popliteal pterygium, polydactyly, cleft lip/palate; ear abnormalities Ped Derm 24:90–92, 2007; J Med Genet 26:417–420, 1989 Downs' syndrome (Trisomy 21) – Simian crease Syndromes of the Head and Neck, p.35, 1990 EEC syndrome – linear cleft; p63 mutation BJD 146:216–220, 2002 Ehlers-Danlos syndrome types I, II, and III – linear scars Encephalocranial lipomatosis (Haberland syndrome) – congenital linear face and scalp lesions (nevus psiloliparus); linear alopecia; linear yellow papules of forehead extending to eyelids; ophthalmologic manifestations; ipsilateral periorbital papules; seizures, mental retardation; mandibular or maxillary ossifying fibromas and odontomas AD 144:266–268, 2008; Ped Derm 22:206–209, 2005; Arch Neurol 22:144–155, 1970; hairless, pink to yellow tumors of scalp in linear configuration; atrophic hairless patches of scalp and face Ped Derm 10:164–168, 1993 Epidermodysplasia verruciformis BJD 121:463–469, 1989; Arch Dermatol Res 278:153–160, 1985

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microphthalmia, coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hennekam syndrome – autosomal recessive; bilateral single palmar crease, intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, preauricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, hirsutism, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006 Hereditary bullous acrokeratotic poikiloderma (Weary) – Kindler’s syndrome? – pseudoainhum and sclerotic bands Int J Dermatol 36:529–533, 1997 Hereditary familial hypertrophic neuropathy – thickened nerves Hereditary sclerosing poikiloderma – generalized poikiloderma; sclerosis of palms and soles; linear hyperkeratotic and sclerotic bands in flexures of arms and legs AD 125:103–106, 1989; AD 100:413–422, 1969 Hermansky-Pudlak syndrome – mucocutaneous granulomatous disease in Hermansky-Pudlak syndrome; butterfly red plaques of face; linear ulcers of groin and vulva; pink plaques of thighs; swollen vulva; indurated nodules of vulva; axillary ulcers, red face JAMADerm 150:1083–1087, 2014 Hunter's syndrome – linear ridges and plaques, linear papules AD 131:81–86, 1995 Hypereosinophilic syndrome in AIDS JAAD 23:202–204, 1990

Fabry's disease – punctate and linear angiectasis AD 131:81–86, 1995; linear perioral telangiectasias AD 126:1655–1656, 1990

Hyper IgE syndrome with coarse facial features – linear scars JAAD 11:653–660, 1984

Faciogenitopopliteal (popliteal-pterygium)syndrome – linear fibrous cord of leg with ulcer AD 124:1443–1444, 1988

Hypohidrotic ectodermal dysplasia with immune deficiency of Zonana; NEMO mutation; linear hyperpigmentation Am J Hum Genet 67:1555–1562, 2000

Familial milia and absent dermatoglyphics – digital flexion contractures, webbed toes, palmoplantar hypohidrosis, painful fissured calluses, acral blistering, simian crease JAAD 59:1050–1063, 2008 Familial transverse nasal hyperpigmentation J Hered 65:157–159, 1974 Fibroblastic rheumatism – linear parallel cords of neck Cutis 100:354, 356–357, 2017 Glucagonoma syndrome – linear band along waistband AD 133:909, 912, 1997; JAAD 12:1032–1039, 1985; Ann Int Med 91:213–215, 1979 Goldenhar syndrome – multiple linear accessory tragi JAAD 50:S11–13, 2004 Goltz’s syndrome (focal dermal hypoplasia) – en coup de sabre lesions, linear alopecia, linear hypopigmented streaks, linear scars JAMADerm 152:209–210, 2016; Cutis 53:309–312, 1994; JAAD 25:879–881, 1991 Hallermann-Streiff syndrome – linear sutural alopecia, partial anodontia, short stature, atrophy and telangiectasia of central face, parrot-like appearance, microphthalmia, cataracts, high-arched palate, small mouth JAAD 50:644, 2004 Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts,

Hypophosphatemic vitamin D-resistant rickets, precocious puberty, and epidermal nevus syndrome AD 133:1557–1561, 1997 Ichthyosis follicularis with atrichia and photophobia (IFAP) – X-linked recessive; linear plantar hyperkeratosis of heels; linear hairless scalp area in female carriers; ichthyosis, atopic dermatitis, alopecia, follicular papules, nail dystrophy, hyperextensible joints, photophobia, cheilitis, growth and psychomotor retardation, recurrent respiratory and skin infections, cryptorchidism, muscular hypotonia, skeletal abnormalities, inguinal hernia, congenital aganglionic megacolon, corneal vascularization and blindness; mutation in MBTPS2(membrane bound transcription factor protease, site 2) (zinc metalloprotease) JAAD 64:716–722, 2011; Am J Med Genet 85:365–368, 1999 Incontinentia pigmenti – linear atrophic, hairless, hypopigmented streaks on legs of women, stage IV JAAD 64:508–515, 2011; AD 139:1163–1170, 2003; Ped Derm 19:550–552, 2002; AD 112:535– 542, 1976; linear warty lesions of palms in late incontinentia pigmenti BJD 143:1102–1103, 2000 KID syndrome – keratosis, ichthyosis, deafness syndrome – linear hyperkeratosis of flexures, elbows, knees; linear hyperkeratotic erythema; fine granular palmoplantar keratoderma Ped Derm 19:285–292, 2002; BJD 122:689–697, 1990 Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK syndrome) – autosomal recessive BJD 153:461, 2005; Acta DV (Stockh) 77:225–227, 1997; AD 125:103–106, 1989 Keratosis palmoplantaris striata

594 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 KLICK syndrome(keratosis linearis with ichthyosis congenital and sclerosing keratoderma and accentuated linear keratoses of flexures) – polycyclic hypopigmented plaques with peripheral scale; hypotrichosis with sparse light colored hair, parallel constricting bands of fingers, linear keratotic bands of wrists and ankles, woolly hair and hypotrichosis simplex; palmoplantar keratoderma, hypohidrosis BJD 164:1113–1116, 2011; Acta DV 77:225–227, 1997; Actas Dermosifiliogr 97:342–344, 2006; BJD 152:155–158, 2005; AD 125:103–106, 1989 Linear atrophoderma of Moulin Eur J Dermatol 10:611–613, 2000 Lipoid proteinosis – string of pearls along eyelid margin; crusted erosions leading to linear pitted scars Ped Derm 18:21–26, 2001 Marfan's syndrome – striae Melkersson-Rosenthal syndrome – personal observation Microphthalmia with linear skin defects syndrome (MLS syndrome) (microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome) (Xp microdeletion syndrome) – X-linked dominant; atrophic linear scars of face and neck; linear red atrophic skin (resembles aplasia cutis); linear skin defects of head and neck (congenital smooth muscle hamartomas) Ped Derm 25:548–552, 2008; Am J Med Genet 124A:202–208, 2004; Ped Derm 14:26–30, 1997; Am J Med Genet 49:229–234, 1994 Microphthalmia and linear skin defects (MLS) – X-linked dominant; bulbous nose; congenital heart defects; differentiate from Goltz’s syndrome; this syndrome may be the same as MIDAS syndrome with central nervous system abnormalities, short stature, developmental delay, hearing loss, and genitourinary abnormalities; monosomy Xp22.2 Ped Derm 37:217–218, 2020 Midface toddler excoriation syndrome (MITES) – linear excoriations; mutation in PR domain containing protein 12(PRDM12) Muir-Torre syndrome – linear sebaceous adenoma AD 133:97–102, 1997 Multicentric reticulohistiocytosis Cutis 34:78–80, 1984 Multiple linear and progressive fibromatosis Ann DV 104:141–146, 1977; Bull Soc Fr Dermatol Syph 83:278–279, 1976 Neurofibromatosis Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – autosomal dominant; basal cell carcinomas, basaloid follicular hamartomas, linear hypo- or hyperpigmented lesions; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microphthalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors (fibromas), mesenteric cysts, cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism, BJD 182:212–217, 2020; BJD 165:30–34, 2011; JAAD 39:853–857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908– 912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004 Nevus comedonicus syndrome – with ipsilateral polysyndactyly and bilateral oligodontia Ped Derm 27:377–379, 2010 Nevus sebaceous syndrome – PTEN mutation; hemimegalencephaly, dilated right ventricle, macrocephaly; association with Wilms’ tumor J Med Genet 40:e111, 2003

Novel fibrosing disorder – subcutaneous fibrotic nodules, progressive distal joint contractures, marfanoid stature, forehead nodules, skin tightening (sclerodermoid changes), palmoplantar nodules, nodules of elbows and knees, linear arrays of nodules later in course; differentiate from Marfan’s syndrome, congenital contractural arachnodactyly, Winchester syndrome, multicentric osteolysis nodulosis and arthropathy (MONA) syndrome BJD 163:1102–1115, 2010 Olmsted syndrome – follicular hyperkeratosis of buttocks and knees; follicular papules; intertrigo, mutilating palmoplantar keratoderma, linear streaky hyperkeratosis, leukokeratosis of the tongue, sparse hair anteriorly JAAD 53:S266–272, 2005; Eur J Derm 13:524–528, 2003; Semin Derm 14:145–151, 1995; JAAD 10:600–610, 1984; Am J Dis Child 33:757–764, 1927; ; linear lesions in flexures Ped Derm 21:603–605, 2004; Ped Derm 20:323–326, 2003; BJD 136:935–938, 1997; AD 132:797–800, 1996; AD 131:738–739, 1995 Pachydermoperiostosis – primary (Touraine-Solente-Gole syndrome)- autosomal dominant – linear folds and furrows of forehead and cheeks, heavy thick eyelids, cutis verticis gyrata; thick skin of hands and feet; palmoplantar hyperhidrosis; enlarged hands JAAD 31:947–953, 1994; JAAD 31:947–953, 1994; Medicine 70:208–214, 1991; AD 124:1831–1834, 1988; secondary – pulmonary disease, lung cancer, carcinoma of the stomach, esophagus, thymus Parry-Romberg syndrome JAAD 56:257–263, 2007 Patau’s syndrome (trisomy 13) – simian crease of hand, loose skin of posterior neck, parieto-occipital scalp defects, abnormal helices, low-set ears, hyperconvex narrow nails, polydactyly Ped Derm 22:270–275, 2005 Poikiloderma congenitale – linear atrophic lesions AD 44:345–348, 1941 Polyostotic fibrous dysplasia with linear epidermal nevi Proteus syndrome – cerebroid thickening of palms and soles (cerebriform connective tissue nevi); linear epidermal nevus, asymmetric disproportionate overgrowth; before second decade – ovarian cystadenoma or parotid monomorphic adenoma; lipomas, regional lipohypoplasia, vascular malformations (capillary, venous, lymphatic), lung cysts, facial phenotype – dolichocephaly, long face, down slanting palpebral fissures and/or mild ptosis, low nasal bridge, wide or anteverted nares, open mouth at rest; dermal hypoplasia, localized hypertrichosis, patchy light scalp hair, phylloid or linear hyperpigmented macules, gingival overgrowth; JAAD 63:799–804, 2010; JAAD 63:1–22, 2010; JAAD 56:353–370, 2007; Am J Med Genet A 143:2944–2958, 2007; JAAD 52:834–838, 2005; JAMA 285:2240–2243, 2001; AD 133:77–80, 1997; JAAD 25:377– 383, 1991; Ped Derm 6:344–345, 1989; AD 125:1109–1114, 1989; Eur J Pediatr 140:5–12, 1983; Birth Defects Orig Artic Ser 15:291– 296, 1979; linear hypopigmented, linear hyperpigmentation, linear hyperpigmented epidermal nevi JAAD 25:377–383, 1991; Ped Derm 5:14–21, 1988; must be distinguished from hemihyperplasia-­ multiple lipomatosis syndrome (CLOVE syndrome) (congenital lipomatous overgrowth, vascular malformation, epidermal nevi) Am J Med Genet 79:311–318, 1998 Pseudoxanthoma elasticum – linear and reticulated yellow papules and plaques JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; AD 124:1559, 1988; PXE and acrosclerosis Proc Roy Soc Med 70:567–570, 1977; horizontal and vertical linear chin creases JAAD 48:620–622, 2003 Restrictive dermopathy – rigid skin with linear ulcers Reticulolinear aplasia cutis congenita of the face and neck – Xp deletion syndrome, MIDAS (microphthalmia, dermal aplasia, sclerocornea), MLS (microphthalmia and linear skin defects), and Gazali-Temple

Linear Lesions

595

syndrome; lethal in males; residual facial scarring in females, short stature, organ malformations BJD 138:1046–1052, 1998

Dermatographism

Richner-Hanhart syndrome (tyrosinemia type II) – autosomal recessive; tyrosine aminotransferase deficiency; chromosome 16q22–q24; painful palmoplantar keratoderma with circumscribed keratoses, linear hyperkeratotic plaques of soles; bullae may occur; dendritic corneal ulcers, mental retardation; palmoplantar hyperhidrosis; signs include tearing, redness, pain and photophobia progressing to superficial and deep dendritic ulcers; mental retardation; aggregated tonofibril bundles on electron microscopy; crystal structures Ped Derm 23:259–261, 2006; J Pediatr 126:266– 269, 1995; AD 130:507–511, 1994; Ann DV 120:139–142, 1993; Dermatol 182:168–171, 1991; AD 126:1342–1346, 1990; Dermatologica 94:286–308, 1947; Klin Monastbl Augenheilkd 100:580–588, 1938

Electrosurgery grounding burn – personal observation

Rudiger syndrome – thick single palmar crease; somatic retardation, flexion contractures of hands, small fingers and nails, ureterovesical stenosis, micropenis, inguinal hernias, coarse facies, cleft soft palate J Pediatr 79:977–981, 1971

Lightning strike – linear burns in skin folds JAAD 64811–824, 2011; Lichtenberg figures; frond-like (ferning pattern) transient nonblanching pink-red erythema beginning 20 minutes to 3.5 hours after the strike and lasting up to 48 hours Cutis 80:141–143, 2007; Arch Neurol 61:977, 2005; Injury 34:367–371, 2003; NEJM 343:1536, 2000; Burns Incl Thermal Inj 13:141–146, 1987; Proc IEE 123:1163–1180, 1976; Memoirs Med Soc London 2:493–507, 1794

Sakati syndrome – patchy alopecia with atrophic skin above ears, submental linear scars, acrocephalopolysyndactyly, short limbs, congenital heart disease, abnormally shaped low-set ears, ear tag, short neck with low hairline J Pediatr 79:104–109, 1971 Segmental odontomaxillary dysplasia (HATS – hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin findings) – localized facial hypertrichosis, commissural lip cleft, hyperlinear palms, abnormal teeth, missing teeth, abnormal spacing Ped Derm 25:491–492, 2008 Steatocystoma multiplex of the nose Ped Derm 17:136–138, 2000 Sly syndrome Smith-Lemli-Opitz syndrome Clin Pediatr 16:665–668, 1977 Sweet’s syndrome – koebnerized lesions Ped Derm 22:525–529, 2005 Tricho-odonto-onycho-ectodermal dysplasia (linear dermal hypoplasia) – hypotrichosis, hypodontia, focal linear dermal hypoplasia of the tip of the nose, irregular hyperpigmentation of the back, bilateral amastia and athelia, nerve hearing loss AD 122: 1047–1053, 1986 Tuberous sclerosis – facial plaque (angiofibroma)

Diving suits – linear abrasions Forceps marks of the face Frictional changes Hypertrophic scar Intravenous drug abuse (IVDA) – sooting tattoos, track marks, tourniquet hyperpigmentation JAAD 69:135–142, 2013 Irritant contact dermatitis – linear purpura of legs due to laser waxing and depilatory Ped Derm 37:190–191, 2020 Linear heel line hyperpigmentation due to heel length socks Ped Derm 30:473–475, 2013 Lip fissure (median lip fissure) Oral Surg 72:10–14, 1991

Mitten line pigmentation in infancy Ped Derm 27:401–402, 2010 Post-traumatic scar Radiation dermatitis Ann DV 127:198–200, 2000 Radiation recall – carboplatin and paclitaxel, doxorubicin, paclitaxel, docetaxel, etoposide, vinorelbine tartrate, gemcitabine, capecitabine, vinblastine sulfate Cutis 91:21–24, 2013; linear red band of thigh – dabrafenib and pazopanib JAMADerm 152:587– 589, 2016 Rituals – skin offerings of Great Sioux Nation tribal ritual AD 148:114–115, 2012 Sock line pigmentation of infancy AD 143:428–430, 2007; BJD 157:1063–1064, 2007 Sports-related scars – karate scars Cutis 67:499–500, 2001 Swimming pool palms – linear red plaques JAAD 27:111, 1992 Traumatic tattoos

Wells' syndrome

VASCULAR TOXINS

Acute hemorrhagic edema of infancy

Arsenical keratoses

Acute leg edema – stria-like distension of the skin AD 138:641–642, 2002

Eosinophilia myalgia syndrome – l-tryptophan Mercury toxicity – erythema stops at Wallace’s lines Smoker's face – increased facial lines

TRAUMA Abrasions Babinski sign, cutaneous Burns – chemical, thermal, ultraviolet Child abuse – linear scratches, purpura, ecchymoses from a whip or stick JAAD 57:371–392, 2007; Ped Derm 23:311–320, 2006; JAAD 5:203–212, 1981; linear and arcuate purpura – human bites Ped Derm 33:223–224, 2016 Collier's stripes Coma bullae – linear bullae Cutis 69:265–268, 2002; JAAD 38:1–17, 1998

Angioma serpiginosum Ital J Pediatr 45:53, 2019 APACHE (acral pseudolymphomatous angiokeratoma of children) – linear scaly red papules of the hand JAAD 48:S15–17, 2003; BJD 145:512–514, 2001; JAAD S209–211, 2001 Arborizing telangiectasia – thighs and calves Arteriosclerosis – ischemic ulcers at pressure sites; linear fissure of heel Cutis marmorata telangiectatica congenita – linear erosions at birth BJD 137:119–122, 1997; JAAD 20:1098–1104, 1989; AD 118:895– 899, 1982 Generalized essential telangiectasia – familial or acquired JAAD 37:321–325, 1997; JAMA 185:909–913, 1963; with predilection for surgical scar JAAD 60:710–711, 2009 Hemangioma, proliferative – linear vascular papules Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.111 Henoch-Schonlein purpura JAMADerm153:1170–1173, 2017

596

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) Am J Med 82:989–997, 1987

LINEAR LESIONS FOLLOWING VEINS

Lymphangioma circumscriptum

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Mondor's disease – superficial periphlebitis of the chest wall JAAD 23:1–18, 1990 PHACES syndrome – ventral linear midline blanching with segmental infantile hemangioma Ped Derm 32:180–187, 2015

Collagen vascular diseases – linear hyperpigmentation overlying veins JAAD 29:1039–1040, 1993

Pigmented purpuric eruption – linear variant; lichen aureus AD 124:1572, 1988

IgG4 disease – swollen nontender nodular temporal artery NEJM 376:775–786, 2017

Polyarteritis nodosa – nodules and ulcers along distribution of blood vessels, mainly lower limbs

Lupus erythematosus – supravenous hyperpigmentation JAAD 43:540–546, 2000

Sinus pericranii – linear blue plaque of central face JAAD 46:934– 941, 2002; vertical red patch on midforehead to nasal root Ped Derm 31:655, 2014

Relapsing polychondritis – superficial thrombophlebitis Medicine 80:173–179, 2000; Medicine 55:193–216, 1976

Temporal arteritis – bilateral forehead necrosis with linear eschars JAAD 63:343–344, 2010 Thrombophlebitis, superficial or deep Vasculitis, including leukocytoclastic vasculitis Verrucous hemangioma J Cutan Pathol 38:740–746, 2011; JAAD 42:516–518, 2000 Vibex – linear traumatic purpura

Rheumatoid arthritis – erythema, papules, and/or hyperpigmentation JAAD 29:1039–1040, 1993 Scleroderma – supravenous erythema, papules, and/or hyperpigmentation; pigment retention over superficial blood vessels in area of depigmentation JAAD 11:265–268, 1984

CONGENITAL DISORDERS Sinus pericranii – alopecic red or blue nodule of scalp with outline of underlying veins within the nodule JAAD 46:934–941, 2002

LINEAR COMEDONAL LESIONS Eccrine nevus with comedones AD 117:357–359, 1981

DRUGS

Epidermal nevi with scattered open comedones

Actinomycin and vincristine JAAD 43:540–546, 2000

Linear basal cell nevus with comedones

Bortezomib – supravenous erythematous eruption followed by hyperpigmentation (persistent supravenous eruption) BJD 158:863– 864, 2008

Linear lichen planopilaris Nevus comedonicus Palmar and plantar lesions of porokeratotic eccrine ostial and dermal duct nevus Unilateral punctate porokeratosis

 INEAR LESIONS FROM KOEBNER PHENOMENON L (DISEASES THAT KOEBNERIZE) Behcet's disease Bullous pemphigoid Darier's disease

Bromodeoxyuridine – linear supravenous papules and erythema JAAD 43:540–546, 2000; AD 122:199–200, 1986; AD 118:1018– 1019, 1982 Calcium gluconate – calcinosis cutis; red nodules along veins Ped Derm 34:356–358, 2017; at IV sites Ped Derm 36:949–950, 2019 Capecitabine – supravenous hyperpigmentation – personal observation Cephalexin infiltration of vein – personal observation Corticosteroids – post-steroid injection atrophy and/or hypopigmentation along draining lymphatics Ped Derm 37:235–236, 2020

Dermatitis herpetiformis

Cyclophosphamide JAAD 43:540–546, 2000; phlebitis JAAD 71:203–214, 2014

Eruptive xanthomas JAAD 33:834–5, 1995

CHOP therapy JAAD 43:540–546, 2000

Erythema multiforme

Dacarbazine AD 118:1018–1019, 1982

Lichen nitidus

Docetaxel – supravenous hyperpigmentation J Eur Acad DV 19:345–347, 2005; BJD 142:1069–1070, 2000

Lichen planus Mastocytosis Molluscum contagiosum Pellagra Pityriasis rubra pilaris Psoriasis Pyoderma gangrenosum Vasculitis Verruca vulgaris Vitiligo

Doxorubicin JAAD 43:540–546, 2000; supravenous urticaria (3%) Cancer Treatment Reports 63:2027–2069, 1979; Cancer Chemotherapy Reports 59:1177–1179, 1975 5-Fluorouracil – erythema or pigmentation overlying veins JAAD 71:203–214, 2014; JAAD 53:5295–30, 2005; JAAD 43:540–546, 2000; JAAD 39:839–842, 1998; AD 129:644–645, 1993; JAAD 25:905, 1991 Fotemustine – pigmentation overlying veins JAAD 39:839–842, 1998 Minocycline – supravenous hyperpigmentation of veins previously treated with sclerotherapy JAAD 44:342–347, 2001 Mitomycin – papules JAAD 43:540–546, 2000

Linear Lesions Following Veins 597 Nitrosourea fotemustine Dermatology 184:70–72, 1994 Polychemotherapy – pigmentation overlying veins JAAD 39:839– 842, 1998 Silver sulfadiazine stain – personal observation Serpentine supravenous hyperpigmentation – 5-fluorouracil, vinorelbine, fotemustine, docetaxel NEJM 363:e8, 2010 Triazinate – pigmentation overlying veins JAAD 39:839–842, 1998 Vinblastine JAAD 43:540–546, 2000 Vinorelbine – pigmentation overlying veins JAAD 39:839–842, 1998; Dermatology 188:244, 1994

EXOGENOUS AGENTS

Sarcoid – presenting as thrombophlebitis Clin J Exp Dermatol 10:592–594, 1985

METABOLIC DISEASES Calcinosis cutis with vein – personal observation Homocystinuria – cystathionine beta-synthase deficiency – superficial thrombophlebitis; marfanoid habitus, malar rash, larger facial pores, livedo reticularis, tissue paper scars, sparse fine hair JAAD 46:161–183, 2002; JAAD 40:279–281, 1999 Hyperparathyroidism – calcinosis with venulitis Liver disease – cirrhosis; caput medusae – portal obstruction and portal hypertension

Sclerotherapy with necrosis J Derm Surg Oncol 15:214–219, 1989

NEOPLASTIC DISEASES INFECTIONS AND INFESTATIONS Bacterial lymphangitis NEJM 372:649, 2015 Cellulitis with lymphangitis

Carcinoma telangiectoides Kaposi's sarcoma – HIV; hyperalgesic pseudothrombophlebitis Metastases – lymphangitic spread of tumor

Dermatophyte cellulitis in saphenous vein surgical site Erysipelas – personal observation

PARANEOPLASTIC DISEASES

Herpes simplex with lymphangitis

Thrombophlebitis migrans (Trousseau’s sign) – superficial and deep venous thromboses of the neck, trunk, or extremities; strong association with internal malignancy Int J Derm 23:205–206, 1984; Cutis 21:763–768, 1978; Circulation 22:780, 1960

HIV – persistent serpentine supravenous hyperpigmentation Skin Med 11:93–94, 2013 Insect bite within vein – personal observation Leishmania braziliensis lymphangitis – personal observation Lyme disease – lymphangitic streaking JAAD 49:363–392, 2003

Acute varicocele – due to renal cancer; serpiginous varicose vein of scrotum NEJM 374:2075, 2016

Lymphangitis NEJM 372:649, 2015 Lymphogranuloma venereum – lymphangitis Int J Dermatol 15:26–33, 1976; Br J Vener Dis 49:193–202, 1973 Mycobacterium tuberculosis – nodular granulomatous phlebitis (phlebitic tuberculid) – nonulcerative subcutaneous nodules along anterior and medial leg veins Am J Clin Dermatol 3:319–328, 2002; Histopathology 30:129–134, 1997 Nocardia – with lymphangitis Clin Dermatol 38:152–159, 2020 Parvovirus B19 – lymphangitis Ped Derm 20:184–186, 2003 Staphylococcus aureus – nodular lymphangitis Ped Derm 34:103– 104, 2017 Tularemia – pustule of toe; lymphangitis of foot Ped Derm 35:478– 481, 2018

INFILTRATIVE DISEASES Amyloidosis – primary systemic; cord-like thickening of blood vessels; vascular amyloid in vessels JAAD 15:379–382, 1986; primary systemic amyloid presenting as dilated veins Am J Med 109:174–175, 2000 Intralymphatic histiocytosis – linear and serpiginous (possibly paraneoplastic, associated with Merkel cell tumor, breast cancer, lung adenocarcinoma) JAMADerm 155:960–961, 2019; Histopathol 24:265–268, 1994

INFLAMMATORY DISEASES Eosinophilic fasciitis – groove sign (sunken veins) JAAD 17:648– 656, 1987

PHOTODERMATOSES Phytophotodermatitis mimicking superficial lymphangitis – supravenous erythema BJD 142:1069–1070, 2000

PRIMARY CUTANEOUS DISEASE Atopic dermatitis lymphangitis – personal observation Frontal fibrosing alopecia – vertical linear depression along frontal veins JAAD 72:1087–1088, 2015 Generalized lipodystrophy – prominence of veins on extremities AD 124:571–576, 1988 Idiopathic Vitiligo – overlying varicose veins

SYNDROMES Adams-Oliver syndrome – autosomal dominant; terminal transverse limb anomalies, aplasia cutis congenita, cutis marmorata telangiectatica congenita, severe growth retardation, aplasia cutis congenita of knee, short palpebral fissures, dilated scalp veins, simple pinnae, skin tags on toes, hemangioma, undescended testes, supernumerary nipples, hypoplastic optic nerve, congenital heart defects Ped Derm 24:651–653, 2007 Antiphospholipid antibody syndrome – thrombophlebitis Semin Arthritis Rheum 31:127–132, 2001; JAAD 36:149–168, 1997; JAAD 36:970–982, 1997; Clin Rheumatol 15:394–398, 1996; South Med J 88:786–788, 1995; BJD 120:419–429, 1989

598 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Behcet’s syndrome – superficial thrombophlebitis Semin Arthritis Rheum 27:197–217, 1998; superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of the neck with neck vein distension, upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008 Ehlers-Danlos syndrome, type IV – prominent venous pattern Hutchinson-Gilford progeria syndrome – prominent scalp veins JAMADerm 150:197–199, 2014 Hypereosinophilic syndrome – superficial venous thrombophlebitis AD 142:1606–1610, 2006 Macrocephaly-capillary malformation syndrome (formerly macrocephaly-­CMTC (cutis marmorata telangiectatica congenita) syndrome) – macrocephalic neonatal hypotonia and developmental delay; distended linear and serpiginous abdominal wall veins, patchy reticulated vascular stain without atrophy; telangiectasias of face and ears; midline facial nevus flammeus, hydrocephalus, skin and joint hypermobility, polydactyly, 2–3 toe syndactyly, frontal bossing, hemihypertrophy with segmental overgrowth JAAD 58:697–702, 2008; Ped Derm 24:555–556, 2007; JAAD 56:541– 564, 2007 (Note: Beckwith-Wiedemann syndrome demonstrates dysmorphic ears, macroglossia, body asymmetry, midfacial vascular stains, visceromegaly with omphalocele, neonatal hypoglycemia, BUT NO MACROCEPHALY); Megalencephaly-polymicrogyria-polydactylyhydrocephalus syndrome – both have macrocephaly, face and limb asymmetry, craniofacial abnormalities, joint laxity or soft skin, distal limb malformation; developmental delay Nat Genet 44:934–940, 2012; Ped Derm 30:541–548, 2013;

TOXINS Eosinophilic myalgia syndrome – supravenular groove Mercury – surreptitious injection of liquid mercury; subcutaneous nodules along veins; embolic to lungs with numerous diffuse high-­density opacities NEJM 369:2031, 2013

TRAUMA Intravenous drug abuse (IVDA) – supravenous hyperpigmentation; thrombophlebitis; septic phlebitis BJD 150:1–10, 2004; thrombosed veins, ulcerated needle tracks, thrombosis of veins, carbon tattoos JAAD 69:135–142, 2013; foreign body granulomas secondary to intravenous drug abuse JAAD 13:869–872, 1985

VASCULAR DISEASES Arborizing telangiectasia – thighs and calves Arteriovenous malformation with unilateral varices – congenital or acquired; red pulsating nodules with overlying telangiectasia – extremities, head, neck, trunk abdominal arteriovenous fistulae – lower extremity cyanosis, pulsatile varicose veins, and scrotal edema Cutis 87:284–286, 2011 Arteriovenous shunt, iatrogenic Bockenheimer’s syndrome (genuine diffuse phlebectasia) (phlebectasia congenita) – extensive venous malformation; diffuse phlebectasia; blue network of dilated veins JAAD 56:541–564, 2007; Ped Derm 23:294–297, 2006; BJD 116:602–603, 1987 Capillary-venous malformation with phlebectasia of the lower limb – hemihypertrophy with small well defined blotchy blue patches

amid prominent leg veins; prominent veins of popliteal fossa, knee, and dorsal foot Ped Derm 30:541–548, 2013; of arm with phlebectasias Ped Derm 32:287–289, 2015 CLAPO syndrome – capillary malformation of lower lip; lymphatic malformation of the face and neck; swollen lip, prominent veins of the neck, jaw, and scalp, asymmetry of face and limbs, partial or generalized overgrowth reticulate erythema of the neck; PIK3CA mutation Ped Derm 35:681–682, 2018 Congestive heart failure – varicosities – personal observation Facial vein pulsation – severe tricuspid regurgitation The Lancet 393:1330, 2019 Hepatic vein thrombosis – generalized varicosities – personal observation Hypertrichosis, linear overlying thrombophlebitis AD 124:30–31, 1988 Klippel-Trenaunay syndrome – varicosities JAAD 61:621–628, 2009; AD n145:1147–1151, 2009; J Ped Orthop 12:401–402, 1992 Lymphangiothrombosis Lymphangitis – chemical, thermal, infectious Mondor's disease(axillary web syndrome) – localized thrombophlebitis of veins or lymphatics of chest wall (thoracic-epigastric and/or lateral thoracic) (also, lower leg) with or without linear depressions AD 141:880–881, 2005; NEJM 352:1024, 2005; JAAD 49:905–906, 2003; JAAD 40:636–638, 1994; Acta Chir Scand 149:33–334, 1983; Arch Int Med 113:881–885, 1964; Mem Acad Chir Paris 65:1271, 1939; Guy’s Hosp Rep Lond 15(series 3)302, 1869–1870; may be caused by drug abuse Arch Surg 125:807–808, 1990; jellyfish sting Med J Aust 157:836–837, 1992; drug-induced lupus erythematosus; hypercoagulable state JAAD 23:1–18, 1990; associated with breast cancer Surgery 103:438–439, 1988; association with lipoma Dermatol Surg 25:563–565, 1999 Multiple progressive angioma – blue compressible nodules on face of children or teenagers; may be distributed along the vein Acta DV (Stockh) 31:304–307, 1951 Non-venereal sclerosing lymphangitis of the penis JAAD 49:916– 918, 2003; Urology 127:987–988, 1982; BJD 104:607–695, 1981; Derm Z 78:24–27, 1938; Munchn Med Wschr 70:1167–1168, 1923 Pigmented purpuric eruption – lichen aureus AD 124:1572–1574, 1988 Polyarteritis nodosa – nodules and ulcers along distribution of blood vessels, mainly lower limbs Portal hypertension – dilated veins around umbilicus JAAD 72:1066–1073, 2015 Stewart-Bluefarb syndrome – arteriovenous malformation of leg with multiple fistulae and port wine stain-like purplish lesions (Mali’s acroangiodermatitis/pseudo-Kaposi’s sarcoma) – brown macules, purple nodules and plaques, edema, varicose veins, hypertrichosis, cutaneous ulcers, enlarged limb JAAD 65:893–906, 2011 Sunburst varicosities and telangiectasia J Derm Surg Oncol 15:184–190, 1989 Superficial lymphangitis with overlying papular and vesicular interface dermatitis following injury Dermatology 203:217–220, 2001 Superficial migratory thrombophlebitis – linear or oval tender red nodules of the legs, abdomen, arms JAAD 45:163–183, 2001; JAAD 23:975–985, 1990 Superficial thrombophlebitis of temporal vein – personal observation Superior vena cava syndrome – venous ectasia of the chest and neck (garland sign) Cutis 79:362, 367–368, 2007; Am Rev Respir Dis 141:1114–1118, 1990 Supravenous hyperpigmentation, idiopathic – personal observation

Lip Lesions, Pigmented Temporal arteritis – linear erythema over temples Arch Surg 1:323–329, 1890 Thromboangiitis obliterans (Buerger’s disease) – recurrent venous thrombosis with supravenous erythema Am J Med Sci 136:567– 580, 1908 Thrombophlebitis, superficial, deep Varicosities NEJM 355:488–498, 2006; Br Med J 300:763–764, 1990 Vascular malformation with underlying disappearing bone (Gorham-­ Stout disease) – skin-colored papulovesicles along a vein JAMA 289:1479–1480, 2003 Vein of Galen malformation – eyelid edema, telangiectatic patches of forehead and cheek, prominent superficial veins of forehead JAMA Derm 149:249–251, 2013 Venous insufficiency with supravenous hyperpigmentation – personal observation Venous stars NEJM 355:488–498, 2006

LIP LESIONS, PIGMENTED JAAD 28:33, 1993

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INFILTRATIVE DISORDERS Erdheim-Chester disease (non-Langerhans cell histiocytosis) – CD68+ and factor XIIIa+; negative for CD1a and S100; xanthoma and xanthelasma-­like lesions (red-brown-yellow papules and plaques); flat wart-like papules of face; lesions occur in folds; skin becomes slack with atrophy of folds and face; also lesions of eyelids, axillae, groin, neck; pretibial dermopathy, pigmented lesions of lips and buccal mucosa; long bone sclerosis; diabetes insipidus, painless exophthalmos, retroperitoneal fibrosis, renal (hairy kidneys), cerebellar syndrome, and pulmonary histiocytic infiltration J Cutan Pathol 38:280–285, 2011; Int J Urol 15:455–456, 2008; Austral J Dermatol 44:194–198, 2003; JAAD 57:1031–1045, 2007; AD 143:952–953, 2007; Hautarzt 52:510–517, 2001; Medicine (Baltimore) 75:157–169, 1996; Virchow Arch Pathol Anat 279:541– 542, 1930

INFLAMMATORY DISEASES Post-inflammatory hyperpigmentation

METABOLIC DISEASES Addison's disease Odontostomatol Trop 11:87–90, 1988

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Vitamins B1 and B2 deficiencies JAAD 15:1263–1264, 1986

Allergic contact dermatitis – cosmetic lip tattoos Contact Dermatitis 63:223–227, 2010

NEOPLASTIC DISEASES

Lupus erythematosus – discoid lupus erythematosus Int J Dermatol 57:830–836, 2018; NEJM 269:1155–1161, 1963

DRUGS Fixed drug eruption – clarithromycin J Res Pharm Pract 2:169–171, 2013Imatinib mesylate – hyperpigmented lichenoid flat-topped papules of trunk and lips Cutis 99:189–192, 2017 Minocycline OSOOPOR 125:e54–56, 2018; J Clin Periodontol 32:119–122, 2005; JAAD 30(pt 1) 802–803, 1994

Actinic cheilitis Community Dental Health 28:60–63, 2011 Basal cell carcinoma, pigmented Benign acquired lentiginosis – personal observation Kaposi’s sarcoma Exp Clin Transplant Jan 2, 2018.doi:10.6002/ect 2017.0075 Labial melanotic macule (benign labial lentigo) Oral Surg Oral Med Oral Pathol 42:192–205, 1976 Lentigo maligna – hyperpigmented lips and oral mucosa AD 138:1216–1220, 2002 Lentigo maligna melanoma

Polychemotherapy for metastasizing ovarian carcinoma G. Ital Dermatol Venereol 124:77–83, 1989

Lentigo simplex

Polymyxin B, intravenous – personal observation

Melanoacanthoma – irregularly pigmented macule of mucosal inner lip JAMADerm 150:563–564, 2014; Med Oral Patol Oral Cir Bucal 17:e919–924, 2012

Quinidine photolichenoid dermatitis

EXOGENOUS AGENTS Amalgam tattoo PLoSone Nov 6, 2018 Bismuth Magnesium

Leukoplakia

Melanocytic nevus, junctional Melanoma BMC Res Notes 8:499, Sept 29, 2015; Oncol Letter 8:1283–1286, 2014; J Dermatol Case Rep 27:1–4, 2012; BJD 152:1324–1326, 2005 Seborrheic keratosis

Silver (argyria) Am J Ind Med 52:246–250, 2009 Tattoo

PHOTODERMATOSES Ephelide

INFECTIONS AND INFESTATIONS AIDS-associated labial lentigo

Lichenoid photodermatitis Solar lentigo

600 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

PRIMARY CUTANEOUS DISEASES Acanthosis nigricans JAAD 31:1–19, 1994

LIP PAPULES

Atopic dermatitis – labial hyperpigmentation in Asian patients Int J Dermatol 57:817–821, 2018

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Fordyce spots – yellow macule BJD 129:355, 1993; BJD 121:669– 670, 1989

CREST syndrome

Lichen planus Clin Case Rep 7:146–148, 2018 Lichen sclerosus – white lesions of lips Ped Derm 23:500–502, 2006 Racial pigmentation Vitiligo – repigmenting

SYNDROMES Albright's syndrome Bandler syndrome – autosomal dominant; perioral, oral hyperpigmented macules; pigmentation of hands and nails; associated with intestinal vascular malformations JAAD 62:171–173, 2010 Carney complex Endocrinol Diabetes Metab Case Rep 2014;2014:140023 Cowden’s disease – personal observation

Lupus erythematosus – bullous LE, discoid lupus erythematosus Lupus May 6, 2020; Clin Dermatol 35:e1–14, 2017; Clin Exp Dermatol 39:563–569, 2014; NEJM 269:1155–1161, 1963

CONGENITAL LESIONS Congenital rhabdomyomatous mesenchymal hamartoma (striated muscle hamartoma) – skin-colored pedunculated (polypoid) nodule of the neck, midline of chin, upper lip Ped Derm 16:65–67, 1999; Ped Derm 7:199–204, 1990; Ped Derm 3:153–157, 1986 Sucking blisters, calluses Ped Derm 4:123–128, 1987

DRUGS d-Penicillamine – for Wilson’s disease; elastosis perforans serpiginosa-­like lip papules J Periodontol 81:1231–1236, 2010

Cronkhite-Canada syndrome Hereditary acrolabial telangiectasia – blue lips, areolae, and nail bed, telangiectasias Idiopathic lenticular pigmentation – oral, labial, perianal, and digital pigmented macules AD 132:844–845, 1996 LAMB/NAME syndrome (Carney complex) Oral Surg 63:175–183, 1987; Medicine 64:270–283, 1985 Laugier-Hunziker syndrome OSOMOPOR 119:374–378, 2015; JAAD 62:171–173, 2010; AD 132:844–845, 1996; Dermatologica 181:183–186, 1990 LEOPARD syndrome Dermatol Online J 14:7, 2008 McCune-Albright syndrome – lentigines of lips; GNAS mutation JAMADerm 150:760–763, 2014; Br J Oral Surg 6:188–191, 1969; JAMA 205:618–626, 1968

EXOGENOUS AGENTS Cosmetic tattoos – sarcoid AD 141:869–872, 2005; granulomatous reaction Int J Dermatol 47:59–60, 2008 Hyaluronic acid injection Am J Dermatopathol 32:306–309, 2010

INFECTIONS AND INFESTATIONS Granuloma inguinale – extragenital lesions of the nose and lips, or extremities; papule or nodule breaks down to form ulcer with overhanging edge; deep extension may occur; or serpiginous extension with vegetative hyperplasia; pubis, genitalia, perineum JAAD 32:153–154, 1995; JAAD 11:433–437, 1984

Neurofibromatosis

Herpes simplex Recent Pat Inflamm Allergy Drug Discov 11:107– 113, 2017

Peutz-Jeghers syndrome – STK11 mutation JAAD 53:660–662, 2005; Curr Prob Derm 14:41–70, 2002; J Dent Child 44:131–134, 1977; J Periodontol 42:726–736, 1971

Leishmaniasis BMC Infect Dis 17:96, 2017; Ann Parasitol 61:197– 199, 2015

TOXINS Arsenic poisoning – chronic BJD 149:757–762, 2003 Heavy metal poisoning – lead poisoning JAAD 67:e295–296, 2012 Smoking-associated melanosis

Leprosy – lepromatous leprosy – histoid nodules of the lip Int J Lepr Other Mycobact Dis 65:374–375, 1997; borderline tuberculoid leprosy mimicking cutaneous T-cell lymphoma SKINmed 11:379– 381, 2013 Molluscum contagiosum Drugs Aging 19:503–514, 2002; J Oral Med 35:62–64, 1980 Mycobacterium tuberculosis – lupus vulgaris SKINMed 9:125–126, 2011

TRAUMA

Paracoccidioidomycosis Braz Dent J 23:753–757, 2012; Mycoses 54:e189–195, 2011

Radiation therapy

Pinta Rhinoscleroma – plaques of nodules of upper lip Oral Dis 26:670– 676, 2020; Arch Pathol Lab Med 142:1533–1536, 2018

VASCULAR LESIONS Venous hemangioma Venous lake

Syphilis, primary (chancre) – ulcerated plaque; secondary – split papules, nodular secondary syphilis Br Dent J 160:237–238, 1986 Tinea faciei Med Mycol 56:E1–5, 2015 Verruca vulgaris; Scientific World Journal 8:507, 2008; Oral Surg Oral Med Oral Pathol 62:410–416, 1986

Lip Papules Yaws

Congenital infantile fibrosarcoma – giant red tumor of lip Ped Derm 31:88–89, 2014

INFILTRATIVE DISORDERS

Cutaneous epithelioid sarcoma-like hemangioendothelioma AD 149:459–465, 2013

Amyloidosis, primary systemic JAAD 77:809–830, 2017; lichen amyloidosis Singapore Med J 48:e165–167, 2007

Cutaneous horn Actas Dermosifiliogr 107:429, 2016; Dermatol Online J 17:10, 2011; Int J Ped Dent 13:365–367, 2003

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – limb contractures, sclerodermoid changes; gigantic lip fibromas, giant fibrous nodules of the scalp and ears; giant nodules of frontal scalp and face; periarticular nodules of knees; gingival hypertrophy, bone deformities; mutation in gene encoding capillary morphogenesis protein 2(ANTRX2(CMG2)) Ped Derm 23:458–464, 2006; JAAD 55:1036–143, 2006; Ped Derm 11:52–60, 1994;Pediatrics 87:228– 234, 1991

Desmoplastic trichilemmoma – white papule of eyelid; lip papule JAAD 76:S22–24, 2017; Dermatol Surg 30:1062–1064, 2004

Juvenile xanthogranuloma Pediatr Dent 39:238–240, 2017 Lichen myxedematosus Langerhans cell histiocytosis J Cutan Pathol 36:1109–1113, 2009 Mucocoele Pseudolymphoma – purple-red papulonodules BJD 170:1204– 1206, 2014 Xanthoma disseminatum (Montgomery's syndrome) – red-yellowbrown lip papules NEJM 338:1138–1143, 1998; JAAD 23:341–346, 1990; AD Syphilol 37:373–402, 1938

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Epidermal nevus Fibroma (irritation fibroma) Folliculosebaceous cystic hamartoma Quintessence Int 42:e75–77, 2011 Fordyce spots – ectopic sebaceous glands; yellow papules of buccal mucosa, lip, penile shaft Pediatr Child Health 23:499–500, 2018 Granular cell tumor Am J Dermatopathol 20:61–64, 1998; J Newark Beth Israel Hosp 12:190–202, 1961 Histiocytosis – crystal storing Head Neck Pathol 6:111–120, 2012 Kaposi’s sarcoma Indian J DV Leprol 76:215, 2010; Oral Surg Oral Med Oral Pathol 71:38–41, 1991 Keratoacanthoma Oral Surg Oral Med Oral Pathol 38:918–927, 1974; associated with permanent lip tattoo JAAD 60:1073–1074, 2009 Leiomyoma J Oral Maxillofac Surg 59:80–83, 2001

INFLAMMATORY DISEASES Cheilitis glandularis Granulomatous cheilitis Kikuchi’s disease J Dermatol 29:587–592, 2002 Lymphocytoma cutis JAAD 38:877–905, 1998 Necrotizing sialometaplasia J Oral Maxillofac Surg 58:1419–1421, 2000 Sarcoidosis Med Oral Patol Oral Cir Biol 15:e456–458, 2010; Br Dent J 205:437–442, 2008; AD 141:869–872, 2005; Otolaryngol Head Neck Surg 131:142, 2004

METABOLIC DISEASES Fabry’s disease – red papules of the face and lips BJD 166:712– 720, 2012; BJD 157:331–337, 2007 Milia-like calcinosis cutis Ped Derm 21:483–485, 2004 Verrucous xanthoma AD 136:665–666,669, 2000; J Oral Maxillofac Surg 51:432–434, 1993

NEOPLASTIC DISORDERS Acquired fibrokeratoma Stat Pearls May 24, 2020 PMID 31424730

Leukemia cutis – chronic lymphocytic leukemia JAMADerm 155:485–486, 2019; chronic lymphocytic leukemia – cutaneous infiltrate in previous lesion of herpes simplex labialis Cancer 76:26–31, 1995 Lymphoma Oral Oncol 29B:225–230, 1993; histiocytic lymphoma; cutaneous Richter syndrome (CLL rapidly developing into large cell lymphoma) Int J Dermatol 28:36–37, 1989; subcutaneous panniculitis-­like T-cell lymphoma – lip papules Ped Derm 32:526– 532, 2015 Lymphomatoid papulosis – ulcerated papule Am J Dermatopathol 34:762–765, 2012; JAAD 44:339–341, 2001 Melanocytic nevus Melanoma – desmoplastic melanoma of the lip – ulcerated nodule, lip ulcer, induration and edema JAAD 47:863–868, 2002; amelanotic melanoma – multilobulated red nodules of lower lip Cutis 92:250–252, 2013; with blue nevus Ann Dermatol 22:119–124, 2010 Merkel cell carcinoma – reddish-blue nodules; legs, lip, eyelid, scalp, nose Histopathology 7:229–249, 1983 Mesothelioma, metastasis Am J Dermatopathol 29:388–391, 2007 Metastases- rhabdomyosarcoma JAAD 58:S118–120, 2008; gastrointestinal carcinoma AD 127:588–589, 1991; renal cell carcinoma Australas J Dermatol 46:158–160, 2005

Actinic keratosis

Microcystic adnexal carcinoma JAAD 45:283–285, 2001; JAAD 41:225–231, 1999; JAAD 29:840–845, 1993

Adenolipoma BJD 148:606–607, 2003

Mucocele AD 101:673–678, 1970

Angiokeratoma Ann DV 139:732–735, 2012

Multinucleate cell angiohistiocytoma Cutis 59:190–192, 1997; Oral Surg Oral Med Oral Pathol 78:743–747, 1994

Angioleiomyoma Int J Oral Maxillofac Surg 24:301–302, 1995 Apocrine gland carcinoma Oral Surg Oral Med Oral Pathol Oral Radiol Endod 82:93–99, 1996 Basal cell carcinoma Dermatol Surg 42:1313–1319, 2016; Acta Pathol Mibrobiol Scand 88A:5–9, 1980 Chondroid syringoma – upper lip Cutis 71:49–55, 2003

Multiple mucocutaneous neuromas (palisaded encapsulated and non-encapsulated neuromas) – lip, palmar, dorsal hand red papules AD 149:498–500, 2013 Neurothekeoma – pink nodule of upper lip Ped Derm 37:187–189, 2020 Palisaded encapsulated neuroma Am Fam Physician 91:869–870, 2015

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Papillary syringoadenoma (syringocystadenoma papilliferum) Sultan Qaboor Univ Med J 14:e575–577, 2014 Pilar sheath acanthoma Int J Trichology 6:185–186, 2014

PSYCHOCUTANEOUS DISEASES Factitial dermatitis

Plasma-acanthoma of the lip Plasmacytoma JAAD 35:777–778, 1996; JAAD 14:335–339, 1986

SYNDROMES

Reticulohistiocytoma AD 139:381–386, 2003; JAAD 46:801, 2002

Birt-Hogg-Dube syndrome – pedunculated lip papules on mucosal surface; thyroid nodules or cysts; mutation in FLCN BJD 162:527– 537, 2010

Rhabdomyoma Am J Dermatopathol 22:264–267, 2000 Rhabdomyosarcoma, congenital – lip nodule Ped Derm 20:335– 338, 2003 Sclerotic fibroma – labial mucosal papulonodule BJD 149:433–435, 2003

Blue rubber bleb nevus syndrome – vascular malformation AD 116:924–929, 1996 Brooke-Spiegler syndrome Indian J DV Leprol 74:632–634, 2008

Sebaceous adenoma

Chronic granulomatous disease SKINMed 4:320–322, 2005

Sebaceous carcinoma JAAD 48:401–408, 2003 Spindle cell carcinoma

Costello syndrome – linear papillomatous papules of upper lip BJD 168:903–904, 2013

Spindle cell hemangioendothelioma

Cowden's syndrome – lip papillomas BJD 148:1040–1046, 2003

Spitz nevus – personal observation

Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC syndrome) – perioral and labial vegetative papillomatous plaques; perleche; high forehead, maxillary hypoplasia, mandibular protrusion Ped Derm 27:658–660, 2010; J Eur Acad DV 17:356–358, 2003; Ped Derm 19:330–332, 2002

Squamous cell carcinoma Ped Derm 26:59–61, 2009;; Otolaryngol Clin North Am 26:265–277, 1993 Syringocystadenoma papilliferum – verrucous papules of upper lip Sultan Qaboos Univ Med J 14:e575–577, 2014 Syringoma Ped Derm 33:e172–173, 2016 Syringomatous carcinoma – papules of upper or lower lip Cutis 77:19–24, 2006 Trichoblastic carcinoma Derm Surg 27:663–666, 2001 Trichofolliculoma Int J Oral Maxillofac Surg 28:135–136, 1999 Trichoepitheliomas BJD 4:269–286, 1892 Trichilemmomas Verrucous carcinoma – arising in lichen planus Cutis 65:219–222, 2000 Verruciform xanthoma Indian Dermatol Online J 7:180–182, 2016; AD 136:665–670, 2000

PHOTODERMATOSES Actinic lichen planus JAAD 20:226–231, 1989 Actinic prurigo Am J Dermatopathol 38:418–422, 2016 Hydroa vacciniforme Chin Med J (Engl)109:645–647, 1996

Focal epithelial hyperplasia (Heck’s disease) – HPV 13,14, 32, 55; Eskimos and South Americans Ped Infect Dis J 29:550–552, 2010; Ped Derm 26:465–468, 2009;; BJD 96:375–380, 1977 Focal palmoplantar and oral mucosa (gingival) hyperkeratosis syndrome (MIM:148730) – palmoplantar keratoderma, leukoplakia, and cutaneous horn of the lips BJD 146:680–683, 2002 Ganglioneuromatosis type III MEN JID November 1994 Goltz's syndrome (focal dermal hypoplasia) – lip and gingival papillomas BJD 160:1116–1118, 2009; asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberry-like papillomas of lips, perineum, acrally, at perineum, buccal mucosa; xerosis; scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones; mutation in PORCN gene (member of porcupine gene family encoding O-acyltransferase that facilitates Wnt protein secretion from endoplasmic reticulum) AD 145:218–219, 2009; JAAD 25:879–881, 1991 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease); Am J Med 82:989–997, 1987

Acanthosis nigricans (cobblestoning)

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) – nodular perianal lesions, ears, lips, gingival hypertrophy, hyperpigmentation, flexion contractures of joints, osteolytic defects, stunted growth Dermatology 190:148–151, 1995; Ped Derm 11:52–60, 1994

Acne rosacea Clin Exp Dermatol 33:743–744, 2008

Lesch-Nyhan syndrome

Acne venenata – due to butter; multiple acne comedones and papules over linear vermilion border Indian J DV Leprol 53:364–365, 1987

Lipoid proteinosis AD 147:857–862, 2011; BJD 156:152–157, 2007; Int J Derm 39:203–204, 2000; Acta Paediatr 85:1003–1005, 1996; JAAD 27:293–297, 1992

Acquired epidermodysplasia verruciformis – personal observation

Multiple endocrine neoplasia syndrome (MEN I) – angiofibromas of vermilion border; facial angiofibromas, lipomas, abdominal collagenomas, cutis verticis gyrate, pedunculated skin tags, acanthosis nigricans, red gingival papules, confetti-like hypopigmented macules; primary hyperparathyroidism with hypercalcemia, kidney stones, prolactinoma, gastrinoma, bilateral adrenal hyperplasia; mutation in menin, a nuclear protein involved in cell cycle regulation and proliferation JAAD 61:319–324, 2009; J Clin Endocrinol Metab 89:5328–5336, 2004; AD 133:853–857, 1997

PRIMARY CUTANEOUS DISEASES

Angiolymphoid hyperplasia with eosinophilia J Cutan Pathol 36:1316–1322, 2009; BJD 145:365, 2001; BJD 134:744–748, 1996 Granuloma annulare Br J Oral Maxillofac Surg 48:234–235, 2010 Granuloma faciale JAAD 53:1002–1009, 2005 Lichen planus JAAD 79:789–804, 2018; J Cut Med Surg 22:232– 233, 2018; BJD 132:1000–1002, 1995; lichen planus sialadenitis J Cutan Pathol 37:396–399, 2010; lichen planus actinicus JAAD 20(pt 1)226–231, 1989 Lichen sclerosus et atrophicus Acta DV Croat 27:195–197, 2019 Reactive perforating collagenosis JAAD 25:1079–1081, 1991

Multiple mucosal neuroma syndrome (MEN IIB) – autosomal dominant; skin-colored papules and nodules of lips, tongue, oral mucosa – medullary carcinoma of the thyroid, mucosal neuromas,

Lip Pits intestinal ganglioneuromas, marfanoid body habitus; RET proto-oncogene JAAD 77:809–830, 2017; NEJM 364:870, 2011; Ped Derm 25:477–478, 2008; JAAD 36:296–300, 1997; NEJM 335:943–951, 1996; Oral Surg 51:516–523, 1981; J Pediatr 86:77–83, 1975; Am J Med 31:163–166, 1961 Multicentric reticulohistiocytosis – lip papules; digital papule; knuckle padsyellow papules and plaques BJD 161:470–472, 2009; AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721–725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968 Neurofibromatosis Contemp Clin Dent 4:512–514, 2013 Nevoid basal cell carcinoma syndrome PTEN hamartoma-tumor syndrome – neuromas of the lips; corneal nerve hypertrophy (as in MEN IIB) AD 142:625–632, 2006 TEMPI syndrome – lip telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting NEJM 367:778–780, 2012;NEJM 366:1843–1845, 2012; NEJM 365:475–477, 2011 Trichorhinophalangeal syndrome I – autosomal dominant; pearshaped nose, tubercle of normal skin below the lower lip, fusiform swelling of the PIP joints; fine brittle sparse hair, eyebrows sparse laterally, dense medially, short stature JAAD 31:331–336, 1994

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Venous lake Clin Exp Dermatol 15:115–118, 1990; varices Indian J Dermatol 59:633, 2014

LIP PITS Angular sinuses Branchio-oculo-facial syndrome – upper lip pits Gene Reviews March 29, 2018 Commissural lip pits – autosomal dominant; usually bilateral may be associated with preauricular sinuses or pits Oral Surg Oral Med Oral Pathol 21:56–60, 1966; may communicate with parotid duct Arch Otolaryngol Head Neck Surg 116:1445–1447, 1990 Congenital sinus of the lower lip (with lower lip pits) (congenital fistulae of lower lip) – bilateral Trans St John’s Hosp Dermatol Soc 61:82–86, 1975 Congenital lower lip pits (congenital fistulae of the lower lip) – associated with formation of cleft lip and/or palate,; isolated lower lip pits Clin Exp Dermatol 43:946–947, 2018; Natl J Maxillofac Surg 5:247–248, 2014; Indian J DV Lerol 80:459–460, 2014; Ped Derm 19:363–364, 2002; Ped Derm 15:443–445, 1998; Cutis 61:127–128, 1998; JAAD 32:520–521, 1995; Am J Hum Genet 6:244–256, 1954; may communicate with underlying salivary glands Congenital upper lip pit Int J Surg Case Rep 51:41–44, 2018

TRAUMA Sucking callus (sucking pads) – in neonates Ped Derm 4:123–128, 1987 Traumatic neuroma J Cutan Pathol 35:320–323, 2008

VASCULAR DISORDERS Acquired progressive lymphangioma Angiofibroma Angiosarcoma Arteriovenous fistula (traumatic) Cutis 62:235–237, 1998 Caliber-persistent arteries of the lip – pulsatile papule Australas J Dermatol 53:e18–19, 2012; Clin Exp Dermatol 31:528–530, 2006; JAAD 46:256–259, 2002; OSOMOPOR Endod 86:308–312, 1998 Epithelioid hemangioendothelioma (pseudomyogenic epithelioid sarcoma-like) Am J Dermatopathol 38:785–786, 2016; JAAD 36:1026–1028, 1997 Epithelioid hemangioma Granulomatosis with polyangiitis JAAD 49:335–337, 2003 Hemangiopericytoma Infantile hemangioma – lip nodules; Ped Derm 30:587–591, 2013; Otolaryngol Clin North Am 19:769–796, 1986; focal hemangioma AD 139:869–875, 2003; associated with enamel hypoplasia Ped Derm 36:899–901, 2019 Intravascular papillary endothelial hyperplasia (Masson’s hemangioma) Cancer 38:1227–1236, 1976 Lymphatic malformation Pyogenic granuloma; J Appl Oral Sci 18:538–541, 2010; Am J Surg Pathol 4:471–479, 1980 Tufted angioma – red lip papule Cutis 78:341–345, 2006; red brown papule J Can Dent Assoc 66:137, 2000; JAAD 20:214–225, 1989; Jpn J Dermatol 59:92–94, 1949; purple red papule of labial mucosa BJD 142:794–799, 2000

Congenital conductive or mixed deafness, preauricular sinus, external ear anomaly, commissural lip pits – autosomal dominant Ann Otol Rhinol Laryngol 100:928–932, 1991 Deafness, preauricular sinus, external ear anomaly, and commissural lip pit syndrome – autosomal dominant; pinna dysplasia, mixed or conductive hearing loss Cutis 88:275–278–280, 2012 Focal dermal hypoplasia, morning glory anomaly, and polymicrogyria – swirling pattern of hypopigmentation, papular hypopigmented and herniated skin lesions of the face, head, hands, and feet, basaloid follicular hamartomas, mild mental retardation, macrocephaly, microphthalmia, unilateral morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly Am J Med Genet 124A:202– 208, 2004 Hirschsprung’s disease with cleft palate and paramedian pits of the lower lip J Pediatr Surg 14:162–164, 1979 Kabuki makeup syndrome(Niikawa-Kuroki syndrome) – lower lip pits and anorectal anomalies, short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high-arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low-set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, cryptorchidism, mental retardation with microcephaly; preauricular dimple/fistula Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 86:282–284, 1999; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 570–573, 1981 Median cleft of the lower lip with lip pits and clefts of the lip and palate Cleft Palate Craniofac J 36:86–87, 1999 Midline sinus of the upper lip Plast Reconstr Surg 65:674–675, 1980

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Orofacial digital syndrome type I – lower lip pits, oral frenula, and clefts, hypoplasia of the nasal cartilage, malformation of the hands, hypertelorism, mental retardation Cutis 61:127–128, 1998

mental retardation; aortic coarctation, progressive bone cysts and jaw tumors Am J Med Genet A 149A:543–545, 2009

Popliteal pterygium (popliteal web) syndrome – autosomal dominant; bilateral popliteal pterygia, intercrural pterygium, hypoplastic digits, absence of labia majora, hypertrophied clitoris, cryptorchidism, bifid scrotum, valgus or varus foot deformities, syndactyly with or without polydactyly, cryptorchidism, umbilical or inguinal hernia, cleft scrotum, lower lip pits, cleft palate, mucous membrane bands (syngnathia) (fibrous bands connecting maxilla and mandible), eyelid adhesions (ankyloblepharon), hypertelorism, defect of alveolar ridge; mutation in IRF6(this mutation also seen in van der Woude syndrome) Ped Derm 28:333–334, 2011: J Med Genet 36:888–892, 1999; Ped Derm 15:443–445, 1998; Int J Pediatr Otorhinolaryngol 15:17–22, 1988

Familial adenomatous polyposis syndrome – lipomas Lancet Oncol 9:462–472, 2008

Trichorrhexis nodosa with lip pits – autosomal dominant ectodermal dysplasia with central nervous system malformations Am J Med Genet 71:226–228, 1997 Van der Woude syndrome – autosomal dominant; lower lip pits, cleft lip, palate, and uvula, hypodontia; mutation of interferon regulatory factor 6(IRF6) Int J Oral Maxillofac Surg 47:421–427, 2018; Ped Derm 29:768–770, 2012; NEJM 351:769–780, 2004; Ped Derm 15:443–445, 1998

LIPOMA SYNDROMES Bannayan-Ruvalcaba syndrome – autosomal dominant; PTEN mutation; may represent pediatric form of Cowden’s syndrome; male predominance Surg Neurol 50:164–168, 1998 Benign symmetrical lipomatosis (Madelung disease, LaunoisBensaude syndrome) – multiple symmetric, nonencapsulated fat masses of the face, neck, other areas; three anterior bulges of the neck; adults 30–60 years old; alcoholism association Aesthetic Plast Surg 28:108–112, 2004 Carbohydrate-deficient glycoprotein syndrome – fat pads or pseudolipomas on the labia and buttock; failure to thrive, mental retardation, ataxia, retinal pigmentary degeneration CLOVE syndrome(congenital lipomatous overgrowth, vascular malformations, and epidermal nevi) – truncal vascular malformations, adipose tissue dysregulation, scoliosis, enlarged bony structures; differentiate from Proteus syndrome with growths at birth; overgrowth is symmetric Am J Med Genet A 146A:2688–2690, 2008

Epidermal nevus syndrome Handb Clin Neurol 111:349–368, 2013

Familial multiple lipomatosis (includes Dercum’s syndrome) – autosomal dominant NEJM 371:1237, 2014; Isr Med Assoc J 4:1121– 1123, 2002 Familial multiple angiolipomatosis Dermatol Online J 13:3, 2007 Familial symmetric lipomatosis (includes Madelung’s deformity) Gardner’s syndrome – autosomal dominant; mutation of APC gene; adenocarcinomas of gastrointestinal tract; multiple lipomas, epidermoid cysts or fibromas; CHRPE (congenital hypertrophy of pigmented retinal epithelium), osteomas of skull, mandible, maxilla, supernumerary teeth Hemihyperplasia syndrome (hemihyperplasia multiple lipomas syndrome) – asymmetric limb growth with lipomas and capillary vascular malformations Am J Med Genet 79:311–318, 1998 Legius syndrome – multiple café au lait macules, skin fold freckling, dysmorphic features, lipomas, mild learning disabilities Rev Neurol 59:209–212, 2014 Lipedema Ann Rehab Med 35:922–927, 2011 MEN type I – lipomas, collagenomas, angiofibromas, café au lait macules Dermatol Online J 18–20, Dec 2012; Lancet Oncol 9:462–472, 2008 MERRF syndrome – horse collar lipomas, ataxia and neuropathy with MERFF II Ekbom’s syndrome; myoclonus, epilepsy, and ragged red fibers) Muscle Nerve 17:843–845, 1994; Multiple lipomas, genital lentigines, intestinal hamartomas, macrocephaly, mental retardation An Bras Dermatol 88:982–985, 2013 Nevus lipomatosis superficialis – unilateral involvement of buttocks most common; usually no extracutaneous findings New Multiple Neoplasm Disorder – case report of patient with family history of multiple cancers, lipomatosis; testicular seminoma, multiple colonic polyps, hyperpigmented skin lesions, renal cancer, pituitary adenoma; negative for PTEN J Med Case Reports 1:9, 2007 Oculocerebrocutaneous syndrome – orbital cysts with anophthalmia or microphthalmia; focal aplastic or hypoplastic hamartomas, skin appendages, and brain malformations Am J Med Genet A 140:709– 726, 2006

Congenital diffuse lipomatosis (Michelin tire baby) – nevus lipomatosis superficialis or smooth muscle hamartoma, symmetric ringed creases of extremities with hirsutism of arms, legs, shoulders, buttocks

Oculoectodermal syndrome (possibly a variant of encephalocraniocutaneous lipomatosis) – epibulbar dermoids, aplasia cutis congenital, craniofacial lipomas Am J Med Genet A 143A:2959– 2962, 2007

Cowden’s disease – autosomal dominant; PTEN mutation Eur J Hum Genet 15:767–773, 2007

Pai syndrome – midline cleft palate, midline facial polyps, and lipoma of central nervous system Int J Oral Maxillofac Surg 48:283–290, 2019

Dercum’s disease (adiposis dolorosa) – painful fatty deposits around upper leg, trunk, arms; menopausal obese women with asthenia, weakness, emotional instability, depression, epilepsy, confusion, dementia Joint Bone Spine 71:147–149, 2004 Elattoproteus syndrome – Proteus-like features with paradoxical overgrowth and lipomas Am J Hum Genet 84:25–28, 1999 Encephalocraniocutaneous lipomatosis (localized Proteus syndrome) – eye anomalies (choristomas); conjunctival desmoid tumors; scarring alopecia; nevus psiloliparus, subcutaneous fatty masses, nodular skin tags, aplastic scalp defects; central nervous system anomalies including intracranial and intraspinal lipomas, congenital abnormalities of the meninges, focal vascular defects;

Pierpont syndrome – X-linked or autosomal dominant; plantar lipomatosis, abnormal facies (high forehead, high anterior hairline, mild midfacial hypoplasia, remarkably narrow and upward slanted palpebral fissures, broad nasal ridge and tip, broad philtrum, bowed upper lip, pouting upper lip, full cheeks, and flat occiput), developmental delay Am J Med Genet A 137:77–80, 2005 Proteus syndrome – multiple lipomas, epidermal nevi, hemangiomas, palmoplantar cerebriform connective tissue nevi Am J Med GenetA 130 A:111–122, 2004 SOLAMEN syndrome – segmental overgrowth, lipomatosis, arteriovenous malformation, epidermal nevus; loss of wild type

Lips, Swollen

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PTEN allele in Cowden families; phenotype mimics Proteus patients Eur J Hum Genet 15:767–773, 2007

DRUG-INDUCED

LIPS, SWOLLEN

Drug reaction with eosinophilia and systemic symptoms (DRESS) – morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, facial edema, lymphadenopathy JAAD 68:693–705, 2013

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergy to food additives, cobalt AD 129:477, 1993 Allergic contact dermatitis to many exogenous agents – oils, waxes, antioxidants; flavorings; latex balloons Cutis 54:138–140, 1994; toothpaste Contact Dermatitis 28:42, 1993; contact orofacial granulomatosis to gold and mercury JAAD 49:1117–1120, 2003; epoxy diacrylates JAAD 38:116–120, 1998; colophonium in dental floss Comm Dent Oral Epidemiol 19:155–159, 1990; toothpaste materials Comm Dent Oral Epidemiol 19:155–159, 1990; Colgate peppermint toothpaste – anaphylaxis Allergy Asthma Clin Immunol 28:6, 2014; oral allergy syndrome – avocado, banana, celery, eggplant, jackfruit, kiwi, mango, strawberry JAAD 53:736–737, 2005; contact urticarial to kiwi fruit Cutis 87:217–220, 2011 Angioedema JAAD 25:155–161, 1991; Dermatol Clin 3:85–95, 1985 Autoantibodies to BP 230 and laminin gamma 1 – bullae of lips, periumbilical bullae, giant bullae of palms BJD 175:619–621, 2016

ACE-inhibitor induced angioedema J Forensic Sci 46:1239–1243, 2001

Fixed drug eruption Int J Dermatol 53:255–258, 2014; JAAD 49:1003–1007, 2003 Isotretinoin – lip abscess JAMADerm 149:960–961, 2013; J Drugs Dermatol 8:1034–1036, 2009 Radiation recall – capecitabine, doxorubicin, taxanes, gemcitabine; erythema and desquamation; edema; vesicles and papules; ulceration and skin necrosis The Oncologist 15:1227–1237, 2010 Tacrolimus, systemic – fibromatosis Hypersensitivity reactions

EXOGENOUS AGENTS Aquagenic angioedema Cutis 37:465–466, 1986 Abreva

Chronic granulomatous disease – cheilitis JAAD 36:899–907, 1997;

Antioxidants Comm Dent Oral Epidemiol 19:155–159, 1990

JAAD 23:444–450, 1990

Benzoates Comm Dent Oral Epidemiol 19:155–159, 1990

Graft vs. host disease, acute OSOMOPOR 121:e51–53, 2016

Calcium hydroxylapatite, injectable JAAD 64:1–34, 2011

Lupus erythematosus, systemic Int J Womens Dermatol 2:96–99, 2016; BJD 121:727–741, 1989; bullous lupus erythematosus Cutis 70:31–34, 2002

Chironoida larvae used as fish food – angioedema Acta DV 78:482–483, 1998

Myeloperoxidase deficiency – lip infection and necrosis Ped Derm 20:519–523, 2003

Cocaine – cracked lips; crack cocaine cheilitis JAAD 69:135–142, 2013

Pemphigus vegetans, Neumann variant JAAD 39:872–875, 1998

Dermal fillers, injectables Br Dent J 227:281–284, 2019

Pemphigus vulgaris – initial presentation Case Rep Dermatol Med 2014:147197Ldoi:10.1155/2014/147197; sole manifestation on lip Dermatol Online J 15:7, 2019

Ecstasy (MDMA) J Forensic Sci 64:1281–1282, 2019; Ned Tijdschr Geneeskd 159:A8665, 2015

Scleroderma

Hyaluronic acid, injectable – lip edema JAAD 64:1–34, 2011

Sjogren’s syndrome – red swollen lip J Dermatol 28:47–49, 2001;

Hydroxymethylmethacrylate/ethylmethacrylate and hyaluronic acid (Dermalive) – granulomatous reaction JAAD 64:1–34, 2011

Urticaria JAAD 50:815–817, 2004; thyroiditis J R Soc Med 96:402–403, 2003

CONGENITAL LESIONS Congenital diffuse infiltrating lipomatosis Eur Arch Pediatr Dent 18:57–63, 2017 Double lip Cutis 66:253–254, 2000 Sucking calluses J Neonatal Perinatal Med 6:281–283, 2013; Ped Derm 4:123–128, 1987

Chocolate – granulomatous cheilitis BJD 150:595, 2004

Flavorings Comm Dent Oral Epidemiol 19:155–159, 1990

Lisinopril – angioedema NY State Dent J 79:25–27, 2013 Monosodium glutamate-related orofacial granulomatosis Oral Surg Oral Med Oral Pathol 71:560–564, 1991 Orthodontic bracket of upper lip – for 10 years Eur J Pediatr Dent 13:239–240, 2012 Polyalkylimide gel (Bio-Alcamid), injectable JAAD 64:1–34, 2011 Silica granuloma – mimics granulomatous cheilitis Dermatologica 181:246–247, 1990 Silicone elastomer (Bioplastique), injectable JAAD 64:1–34, 2011 Sorbic acid – non-allergic urticaria

DEGENERATIVE LESIONS Mucous cyst (mucocele) J Pharm Biollied Sci 7:S731–73, 2015; Eur J Pediatr Dent 13:143–146, 2012

Tattooing, cosmetic AD 141:918–919, 2005 Vitamin A oil – self injection Int J Womens Dermatol 5:126–128, 2018

606 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFECTIONS AND/OR INFESTATIONS Abscess of minor salivary gland – personal observation Actinomycosis – of upper lip Br J Oral Maxillofac Surg 33:248–249, 1995 Anthrax – contact with contaminated meat, carcasses or animal products; hides, hair wool, bore meal, and animal feeds; painless pruritic papule develops vesicle with prominent edema, ulcer, black eschar; enlarging lesion Arch Iran Med 12:320,325–326, 2009; OSOMOPOR 116:E490–492, 2013; Ped Derm 18:456–457, 2001 Balamuthiasis (Balamuthia mandrillaris) – amoebic infection of soft tissues and central nervous system; edematous erythematous infiltrated plaque of the face, abdomen, extremities Advances Dermatol 23:335–350, 2007 Cancrum oris (noma) – labial and buccal necrosis J Dent Child 48:138–141, 1981 Candidiasis – chronic mucocutaneous candidiasis Chlamydia pneumonia – MIRM-like syndrome with cheilitis, penile erosions, morbilliform eruption Ped Derm 34:465–472, 2017 Conidiobolus coronatus Bull Soc Pathol Exot 101:14–16, 2008 Cysticercosis Head Neck 23:497–499, 2001; Br Dent J 170:105– 106, 1991 Dentoalveolar abscess JAAD 50:815–817, 2004 Diphtheria Indian J Pediatr 41:54–56, 1974; Pediatriia 4:81–82, 1954

Mycoplasma pneumonia (MIRM) – erosive eyelid dermatitis, hemorrhagic erosive cheilitis, penile erosions, perianal erosions JAMADerm 156:144–150, 2020 Nasal septal abscess – nasal septal abscess – collection of pus between cartilaginous or bony septum and mucoperichondrium or periosteum; due to trauma; bilateral nasal obstruction, foreign body sensation, nasal pain, swelling and erythema of overlying skin, rhinorrhea, swollen upper lip, fever, headache, malaise J Emerg Med 46:e81, 2014; Pediatr and Neonatology 53:213–215, 2012; Ear, Nose, and Throat J 90:144–145, 2011; J Laryngol and Otol 124:1014–1016, 2010; Rhinology 47:476–477, 2009 Orf Br Dent J 173:343–344, 1992 Paracoccidioidomycosis Dermatol Clin 26:257–269, 2008; J Contemp Dent Pract 8:92–98, 2007; JAAD 31:S91–S102, 1994; Rev Bras Med 28:464, 1971 Parvovirus B 19, including papular-purpuric "gloves and socks" syndrome – swollen lips with painful erosions JAAD 41:793–796, 1999 Phaeoacremonium inflatipes – fungemia in child with aplastic anemia; swelling and necrosis of lips, periorbital edema, neck swelling Clin Inf Dis 40:1067–1068, 2005 Phlegmon – MRSA – personal observation Post-infectious lymphedema of lips Rhinoscleroma – upper lip swelling Cutis 40:101–103, 1987 Staphylococcus aureus J Emerg Med 49:8–11, 2015

Elephantiasis nostras of the lips – presumed streptococcal infection Oral Surg Oral Med Oral Pathol Endod 84:297–300, 1997

Stenotrophomonas maltophilia – lip edema with ulcers AD 149:495–497, 2013

Epstein-Barr virus – swollen erythema of face with swollen lips BJD 143:1351–1353, 2000

Syphilis – primary chancre – ulcerated papule with edema of lip; cheilitis granulomatosa AD 141:1085–1091, 2005; AD 141:1080– 1082, 2005; JAAD 23:444–450, 1990; AD 124:1705–1710, 1988

Erysipelas Furuncle BMC Infect Dis 15:402, 2015; OMOPOR Endod 84:297– 300, 1997 Hand foot and mouth disease (Coxsackie virus) Herpes simplex infection; primary herpetic gingivostomatitis Herpes zoster – mandibular branch of trigeminal nerve BMJ Case Rep 2014 April 15, 2014:bcr2014204439.doi:10.1136/bcr2014– 204459; Ramsay Hunt syndrome – facial nerve Neurology 82:1664, 2014 HIV – granulomatous cheilitis – lip swelling JAMADerm 151:1369– 1370, 2015

Tinea faciei (kerion) AD 142:1059–1064, 2006; Arch Derm Syphilol 61:492–495, 1950 Trichinosis Vaccinia Br Dent J 143:57–59, 1977 Verruca vulgaris Yaws

INFILTRATIVE

Human fascioliasis BMC Infect Dis Dec 23, 2015

Amyloidosis – primary systemic Br Dent J 199:433–435, 2005; JAAD 50:815–817, 2004; Ned Tijdschr Tandheelkd 102:55, 1995

Impetigo Clin Ped (Phila)42:475–482, 2003; acute necrotizing swelling of lower lip OSOMOPOR 113:e224, 2012

Idiopathic lymphoplasmacellular mucositis J Cutan Pathol 44:776– 780, 2017

Insect bite reaction

Plasma cell orificial mucositis (plaque) AD 124:1871–1872, 1988; plasma cell cheilitis – with lip ulcer J Clin Diagn Res 10:2001–2003, 2016; JAAD 30:789–780, 1994

Larva migrans Leishmaniasis Mycoses 41 Suppl2:78–80, 1998 (German); JAAD 28:495–496, 1993; Dermatologica 150:292–294, 1975; L. aethiopica – lip edema Trans R Soc Trop Med Hyg 63:708–737, 1969; espundia (mucocutaneous leishmaniasis) – nasopharyngeal mutilation with protuberant lips Am J Trop Med Hyg 59:49–52, 1998 Leprosy Indian J Lepr 72:245, 2000; Indian J Lepr 71:341–342, 1999, Int J Lepr Other Mycobact dis 65:374–375, 1997 Mycobacterium tuberculosis – cheilitis granulomatosa AD 141:1085–1091, 2005; AD 141:1080–1082, 2005; JAAD 23:444– 450, 1990; AD 124:1705–1710, 1988; macrocheilia Clin Exp Dermatol 28:245–250, 2003

INFLAMMATORY Cheilitis granulomatosa of Miescher – idiopathic monosymptomatic variant of Melkersson-Rosenthal syndrome JAMADerm 151:219– 220, 2015; JAAD 71:407–410, 2014; AD 145:77–82, 2009; AD 141:1085–1091, 2005; AD 141:1080–1082, 2005; JAAD 23:444– 450, 1990; AD 124:1705–1710, 1988 Crohn's disease – orofacial granulomatosis NEJM 373:1250, 2015; JAAD 49:952–954, 2003; AD 135:439–442, 1999; Ped Derm 16:39–42, 1999; JAAD 36:697–704, 1997; cheilitis granulomatosa Ped Derm 35:566–574, 2018; JAAD 68:189–209, 2013; AD

Lips, Swollen 141:1085–1091, 2005; AD 141:1080–1082, 2005; JAAD 23:444– 450, 1990; AD 124:1705–1710, 1988 Erythema multiforme Lancet 392:592, 2018; Medicine 68:133–140, 1989; JAAD 8:763–765, 1983; Stevens-Johnson syndrome Int J Derm 24:587–591, 1985 Granulation tissue

607

NEOPLASTIC Actinic cheilitis J Derm Surg Oncol 7:289–295, 1981 Dentigerous cyst Eur Arch Otorhinolaryngol 262:246–249, 2005 Epidermoid cyst Case Rep Otolaryngol 2014:540910. doi.10.1155/2014/540910

Orofacial granulomatosis – oral lesions with non-caseating granulomas; includes Crohn’s disease, tooth-associated infections, sarcoid, food or contact allergens Dermatol Clin 14:371–419, 1996; facial edema with swelling of lips, cheeks, eyelids, forehead, mucosal tags, mucosal cobblestoning, gingivitis, oral aphthae; including Melkersson-Rosenthal syndrome, Miescher's granulomatous cheilitis BJD 171:423–425, 2014; BJD 170:794–801, 2014; JAAD 62:611–620, 2010; AD 124:1706, 1709, 1988; Crohn's disease, sarcoid, allergy to food additives or cobalt BJD 143:1119– 1121, 2000; Quintessence International 28:265–269, 1997; AD 129:477–480, 1993; in solid orang transplanted children Transplantation 89:606–611, 2010; monosodium glutamate OSOMOP 71:560–564, 1991

Epstein-Barr virus associated lymphoproliferative lesions Ped Blood Cancer 63:2042–2045, 2016; BJD 151:372–380, 2004

Pyoderma gangrenosum Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988

Lymphoma – T-cell lymphoma mimicking Crohn’s disease Oral Oncol 29B:225–230, 1993; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – lip edema, facial edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 72:21–34, 2015; J Dermatol 41:29–39, 2014; JAAD 69:112–119, 2013; Ped Derm 29:96–100, 2012; variant of extranodal NK/T-cell lymphoma, nasal type/ CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of hands, subcutaneous nodules; systemic manifestations; occurs on both sun-exposed and non-sun-exposed skin Int J Dermatol 52:763–765, 2013; Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998; cutaneous T-cell lymphoma Dermatol Online J 14:16, 2008

Sarcoid – granulomatous cheilitis AD 141:1085–1091, 2005; AD 141:1080–1082, 2005; Lupus 1:129–131, 1992; JAAD 23:444–450, 1990; AD 124:1705–1710, 1988; BJD 115:619–622, 1986; J Oral Surg 34:237–244, 1976 Toxic epidermal necrolysis BMJ Case Rep Oct 12, 2018

METABOLIC Acromegaly Ned Tijdschr Tandheelkd 111:20–22, 2004 Congenital neutropenia Cyclic neutropenia Cystic fibrosis with zinc deficiency – personal observation Fabry’s disease Proc R Soc Med 57:143–144, 1964 Hunter’s syndrome – X-linked recessive; macrocheilia; reticulated 2–10-mm-skin-colored papules over scapulae, chest, neck, arms; MPS type II; iduronate-2 sulfatase deficiency; lysosomal accumulation of heparin sulfate and dermatan sulfate; short stature, coarse facies, macroglossia, clear corneas (unlike Hurler’s syndrome), progressive neurodegeneration, communicating hydrocephalus, valvular and ischemic heart disease, lower respiratory tract infections, adenotonsillar hypertrophy, otitis media, obstructive sleep apnea, diarrhea, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), widely spaced teeth, dolichocephaly, deafness, retinal degeneration, inguinal and umbilical hernias Ped Derm 21:679–681, 2004 Hurler's syndrome; Oral Surg 32:46–57, 1971 Hypothyroidism NEJM 283:101, 1970 Lesch-Nyhan syndrome – X-linked recessive; hypoxanthineguanine phosphoribosyltransferase deficiency; self-mutilation; biting of lower lip AD 94:194–195, 1966 Pyostomatitis vegetans – lip ulcers; lip swelling with cobblestoning, micropustules Ned Tijdschr Tandheelkd 125:15–20, 2018; NEJM 368:1918, 2013; Clin Gastroenterol Hepatol 3:886–891, 2005; in Crohn’s disease World J Gastroenterol 22:5655–5667, 2016

Glomus tumor J Nihon Univ Sch Dent 37:97–101, 1995 Granular cell schwannoma – linear plaque AD 121:1197–1202, 1985 Kaposi’s sarcoma J Invest clin Dent 5:161–162, 2014 Leukemic macrocheilia – acute myelogenous leukemia BJD 151:1102, 2004; JAAD 14:353–358, 1986; acute promyelocytic leukemia Rev Stomatol Clin Maxillofac Chir Orale 117:161–163, 2016; hairy cell leukemia JAAD 14(pt 2)353–358, 1986 Leukoplakia Lipoma J Am Dent Assoc 117:849–850, 1988

Lymphomatoid granulomatosis (angiocentric lymphoma) – presenting as angioedema Postgrad Med J 68:366–368, 1992 Melanoma – desmoplastic melanoma of lip; induration and edema JAAD 47:863–868, 2002 Metastasis – esophageal carcinoma Vojinosanit Pregl 71:975–977, 2014 Microcystic adnexal carcinoma Oral Oncol 39:195–198, 2003 Mucocele (ranula) BMC Oral Health June 7, 2010 Multiple myeloma Br Dent J 199:433–435, 2005 Neurofibroma Pleomorphic adenoma J Can Res Ther 11:1025, 2015; Niger J Med 24:277–280, 2015 Rhabdomyomatous mesenchymal hamartoma – swollen lip Ped Derm 32:256–262, 2015 Schwannoma Niger Postgrad Med J 24:191–193, 2017; Ann Maxillofac Surg 3:98–99, 2013 Squamous cell carcinoma Iran Red Crescent Me J 2015 March 17:e13478.doi:10.5812/ircmj13478 Verrucous carcinoma – oral florid papillomatosis of the lip BJD 151:727–729, 2004

Vitamin B1 and B2 deficiencies – red lips, angular cheilitis Ped Derm 16:95–102, 1999; JAAD 15:1263–1274, 1986

PARANEOPLASTIC DISEASES Paraneoplastic pemphigus Dermatol Online J Feb 15, 108; 24(2):13030/qt46ZOV7jv

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PHOTODERMATITIS

SYNDROMES

Actinic cheilitis granulomatosa – UVB sensitivity J Dermatol 19:556–562, 1992

Ackerman syndrome – taurodontism, pyramidal and fused molar roots, juvenile glaucoma, unusual upper lip Am J Phys Anthropol 38:681–694, 1973

Actinic prurigo BJD 144:194–196, 2001; JAAD 44:952–956, 2001; Ped Derm 17:432–435, 2000; JAAD 26:683–692, 1992; Oral Surg Oral Med Oral Pathol 65:327–332, 1988; Ped Derm 3:384–389, 1986; JAAD 5:183–190, 1981

PRIMARY CUTANEOUS DISEASE Acanthosis nigricans JAAD 31:1–19, 1994 Acne vulgaris – cyst Atopic cheilitis Allergy 46:125–128, 1991; Dermatologica 177:360– 364, 1988 Cheilitis exfoliativa – personal observation J Oral Pathol Med 24:177–179, 1995; Arch Derm Syphilol 57:495, 1948; Proc R Soc Med 25:1548–1549, 1932 Cheilitis glandularis(Volkmann’s cheilitis) (Puente’s disease) – inflammatory condition of the lower lip minor salivary glands; enlargement with a mucus ductal discharge, crusts and scale eversion, and hardening of the lip; deep-seated abscesses and fistulae JAAD 62:233–238, 2010; JAAD 57:531–532, 2007; BJD 148:362, 2003; Oral Surg Oral Med Oral Pathol 78:319–322, 1994; Oral Surg Oral Med Oral Pathol 62:654–656, 1986 J Derm Surg 1:372–375, 1985 Collodion baby – eclabium; congenital erythroderma, ectropion, deformed ears, alopecia; mutation in ABCA12 BJD 166:218–221, 2012 Congenital sensory neuropathy with anhidrosis – lip erosions Ped Derm 11:231–236, 1994 Harlequin fetus(ichthyosis congenital fetalis) – autosomal recessive; eclabian; ectropion; rigid plates; severe non-bullous ichthyosiform erythroderma or mild erythrodermic ichthyosis; ABCA 12(adenosine triphosphate binding cassette A12); keratinocyte lipid transfer associated with lamellar granule formation and lipid transfer via lamellar granules on the surface of keratinocytes AD 142:914–918, 2006; BJD 153:811–814, 2005; Curr Prob Derm 14:71–116, 2002; JAAD 212:335–339, 1989; Ped Derm 6:216–221, 1989; Int J Derm 21:347–348, 1982 Hydroa vacciniforme – cheilitis with lip ulcers Ped Derm 21:555– 557, 2004; lip edema AD 142:651, 2006; EBV-associated lymphoproliferative disorders Eur J Dermatol 29:21–28, 2019 Idiopathic macrocheilia BMJ Case Rep Sept 27, 2018; J Dermatol 35:234–237, 2008

Ascher's syndrome – blepharochalasis with progressive enlargement of upper lip; increased thickness of eyelids AD 139:1075– 1080, 2003; JAAD 29:650–651, 1993; Ped Derm 8:122–123, 1991; BJD 66:129–138, 1954; Klin Monatsbl Augenheilkd 65:86–97, 1920; double lip Nigor J Clin Pract 22:1029–1031, 2019; Indian J Plast Surg 44:147–149, 2011 Beare-Stevenson syndrome – cutis gyrata (furrowed skin), acanthosis nigricans, hypertelorism, swollen lips, swollen fingers, prominent eyes, ear anomalies, and umbilical herniation Skin and Allergy News p.37, Sept 2000 Char syndrome – short philtrum, patulous lips, ptosis, low-set pinnae Birth Defects 14(6B):303–305, 1978 Coffin-Lowry syndrome – everted lips with wide mouth, patulous lips, prominent lower lip Am J Med Genet A 164A:516–521, 2014; J Med Genet 25:344–348, 1988 Coffin-Siris syndrome Brain Dev 37:527–536, 2015 Costello syndrome – coarse face with furrowed forehead and scalp, broad nose, wide anteverted nares, thick lips, dysplastic ears Ped Derm 30:665–673, 2013 Cowden's syndrome – papillomatosis of lips Eur J Gastroenterol Hepatol 19:513–517, 2019; BJD 148:1040–1046, 2003 Darier’s disease Indian J Dent Res 22:843–846, 2011 Double lip Down's syndrome Ectodermal dysplasia/skin fragility syndrome – autosomal recessive (Carvajal-Huerta syndrome); skin peeling; generalized erythema and peeling at birth; very short stature, superficial skin fragility with crusts of the face, knees, alopecia of scalp and eyebrows, perioral hyperkeratosis with fissuring and cheilitis, thick dystrophic cracking finger and toenail dystrophy, keratotic plaques on limbs, diffuse or focal striate palmoplantar keratoderma with painful fissuring; PKP1 gene (encoding plakophilin 1) or DSP (encoding desmoplakin); follicular hyperkeratosis of knees; woolly hair; perianal erythema and erosions; cardiomyopathy associated with mutation in desmoplakin not with plakophilin Derm Clin 28:125–129, 2010; BJD 160: 692–697, 2009; JAAD 55:157–161, 2006; Acta DV 85:394–399, 2005; JID 122:1321–1324, 2004; Curr Prob Derm 14:71–116, 2002; Hum Molec Genet 9:2761–2766, 2000; Hum Molec Genet 8:143– 148, 1999 Familial cold urticaria Br Dent J 175:417–418, 1993

Juvenile spring eruption – vesicles of helices and vermilion of lips JAMADerm 154:1356–1357, 2018

Facial edema with eosinophilia

Lichen myxedematosus (scleromyxedema) Int J Dermatol 58:e100– 102, 2019; An Bras Dermatol 94:462–469, 2019

Fountain syndrome – coarse face with progressive swelling of lips, mental retardation, sensorineural deafness, and musculoskeletal abnormalities J Med Genet 26:722–724, 1989

Lichen planus Mayo Clin Proc 92:1053–1060, 2017; BJD 132:1000– 1002, 1995 Lip licker’s cheilitis – personal observation Premature dermatochalasis

PSYCHOCUTANEOUS DISORDERS Factitial cheilitis Ped Derm 32:604–608, 2015; Ped Derm 16:12–15, 1999; exfoliative cheilitis Cureus 10:e2565, 2018; Int J Dermatol 57:885–893, 2018; AD 117:338–340, 1981

Familial idiopathic macrocheilia

Fucosidosis type III GAPO syndrome – growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy; midface hypoplasia; frontal bossing, wide anterior fontanelle, saddle nose, protruding thick lips, low-set ears, anti-Mongoloid slant, diffuse scalp hypotrichosis, prominent scalp veins, sparse eyebrows and eyelashes, absent teeth, slightly redundant skin, impacted teeth Ped Derm 27156–161, 2010; Ped Derm 19:226, 2002; J Craniofac Genet Dev Biol 19:189–200, 1999; Birth Defects 24:205–207, 1988; Am J Med Genet 19:209–216, 1984; Syndr Ident 8:14–16, 1982; Odont Tilster 55:484–493, 1947

Lips, Swollen

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Gingival fibromatosis

Neurofibromatosis

Hennekam syndrome – autosomal recessive; bilateral single palmar crease, intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis, multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, preauricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygia colli, hirsutism, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006

Oral-facial-digital syndrome type I (Papillon-Leage and Psamme syndrome) – X-linked dominant; facial milia, micrognathia, frontal bossing, cleft lip and palate, early eruption of central incisors, dry scalp with thin hair, brachydactyly, clinodactyly of 5th fingers, polydactyly, hydrocephalus, agenesis of the corpus callosum, bifid or multilobulated tongue, hypertrophied lip, labial frenula Pediatrics 29:985–995, 1962; Rev Stomatol 55:209–227, 1954 PHACES syndrome J Pediatr 122:379–384, 1993

Hereditary angioedema – facial, lip, eyelids, tongue, hand edema; prodrome of erythema marginatum (annular urticarial eruption) NEJM 382:1136–1148, 2020; JAAD 65:843–850, 2011

Setleis syndrome – type III – focal facial dermal dysplasias; TWIST2 mutation Clin Dysmorphol 26:128–131, 2017; BJD 130:645–649, 1994

Hughes syndrome – acromegaloid features and thickened oral mucosa; thickened fissured lips J Med Genet 22:119–125, 1985

Smith-Magenis syndrome – upper lip eversion, brachycephaly, midface hypoplasia, prognathism, short broad hands with short fingers, clinodactyly of fifth fingers, fingertip pads, mental retardation Am J Med Genet 41:225–229, 1991

Hypochondrodysplasia – acanthosis nigricans, short stature, frontal bossing, high forehead, prognathism, thick lips, large broad hands Ped Derm 27:664–666, 2010; J Bone Jt Surg 51A:728–736, 1969 Kabuki makeup syndrome (Niikawa-Kuroki syndrome) – short stature, congenital heart defects, distinct expressionless face (frontal bossing, long palpebral fissures, eversion of the lower eyelids, sparse arched lateral eyebrows, epicanthus, telecanthus, prominent eyelashes, short flat nose with anteversion of the tip, short philtrum, large mouth with thick lips, high-arched palate, cleft palate, dental malocclusion, micrognathia, large protuberant low-set ears with thick helix), lowcut hairline, vitiligo, cutis laxa, hyperextensible joints, syndactyly of toes 2–3, brachydactyly, clinodactyly, fetal finger pads with abnormal dermatoglyphics, short great toes, blue sclerae, lower lip pits, cryptorchidism, mental retardation with microcephaly; preauricular dimple/fistula Ped Derm 24:309–312, 2007; JAAD S247–251, 2005; Am J Med Genet 132A:260–262, 2005; Am J Med Genet 94:170–173, 2000; Am J Med Genet 31:565–589, 1988; J Pediatr 105:849–850, 1984; J Pediatr 99:565–569, 570–573, 1981 Kawasaki's disease – mucocutaneous lymph node syndrome – cheilitis J Clin Rheumatol May 21, 2019; Int J Clin Pediatr Dent 11:532–535, 2018; Arch Rheumatol 33:238–240, 2017; Ped Derm 20:511–513, 2003 Keratosis-ichthyosis-deafness syndrome – bright red thickened lips; hyperkeratotic papules and plaques of face, scalp, trunk, extremities; exaggerated diaper dermatitis Ped Derm 13:105–113, 1996; BJD 122:689–697, 1990 Kimura’s disease Ann DV 140:699–703, 2013

Scheie syndrome

Sturge-Weber syndrome (encephalofacial angiomatosis) – facial port wine stain with homolateral leptomeningeal angiomatosis J Pharm Bioallied Sci 4:S349–352, 2012; OSOMOP 22:490–497, 1966 Sweet’s syndrome JAAD 53:S135–138, 2005 Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – macrocheilia, poikiloderma, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation Ped Derm 14:441–445, 1997; JAAD 44:891– 920, 2001 X-linked anhidrotic ectodermal dysplasia X-linked ectodermal dysplasia with immunodeficiency – NEMO mutation; erythroderma, alopecia, red scaly scalp, frontal bossing, periorbital wrinkling, intertrigo, thick everted lower lip AD 144:342– 346, 2008 Williams syndrome – premature laxity of skin, congenital heart disease (supravalvular aortic stenosis), baggy eyes, full cheeks, prominent lips, dental malocclusion, delayed motor skills, cocktail party personality J Pediatr 113:318–326, 1988 Winchester syndrome – lip hypertrophy, diffuse thickening, hyperpigmentation, hypertrichosis Ped Derm 21:1541–59, 2004

Leprechaunism (Donohue syndrome) Ann Genet 30:221–227, 1987

TOXINS

Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high pitched voice; mutation in RIN2 JAAD 66:842–851, 2012

Amanita muscaria mushrooms – ingestion; cholinergic mushroom toxicosis; swollen lips and tongue; altered mental status, vomiting, diarrhea, incontinence, sweating, excess salivation MMWR 68:4834–84, 2019

Melkersson-Rosenthal syndrome (granulomatous cheilitis) Ped Derm 34:479–480, 2017; AD 145:77–82, 2009; AD 144:1627–1630, 2008; Dermatol Clin 14:371–379, 1996; JAAD 21:1263–1270, 1989

TRAUMATIC

Maroteaux-Lamy syndrome (MPS VI) Helv Paediatr Acta 25:337– 362, 1970

Child abuse – large dome-shaped hematomas Ped Derm 23:3113– 20, 2006; Emerg Med Clin North Am 18:6016–17, 2000

Multicentric reticulohistiocytosis Dermatol Online J 10:11. Oct, 15, 2004; OSOMOP 65:721–725, 1988

Electrical burn – child chewing electrical wire

Multiple mucosal neuroma syndrome IIB – thick fleshy everted lips with papules JAMADerm 152:939–940, 2016; AD 139:1647–1652, 2003; JAAD 42:939–969, 2000; Ped Derm 8:124–128, 1991; type III – mucosal neuromas, rubbery swollen lips Br J Oral Maxillofac Surg 20:317–321, 1996

Hematoma

Naxos syndrome – personal observation

Fire-related inhalational injury NEJM 375:4644–69, 2016 Intubation – pressure necrosis of the lip Anesthetis 24:1361–37, 1975 Physical trauma Sunburn

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Surgery – prolonged intubation with pressure ulceration of mucosal surface of lower lip and accompanying edema

Linear IgA disease

Trumpet cheilitis AD 144:6906–91, 2008

Morbilliform eruption

Vibratory angioedema – lower lip edema in saxophonist Contact Dermatitis 20:3463–47, 2009

Nail discoloration

Lupus-like syndrome

Nail dystrophy Onychomadesis

VASCULAR

Oral ulcers

Arteriovenous malformation

Palmoplantar pustulosis

Caliber persistent labial artery (CPLA) Clin Exp Dermatol 31:5285– 30, 2006

Pruritic papular eruption of elbows

CLAPO syndrome – capillary malformation of lower lip; lymphatic malformation of the face and neck; swollen lip, prominent veins of the neck, jaw, and scalp, asymmetry of face and limbs, partial or generalized overgrowth reticulate erythema of the neck; PIK3CA mutation Ped Derm 35:6816–82, 2018

Psoriasis

Elephantiasis nostras Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:2973–00, 1997; J Allergy Clin Immunol 75:4504–51, 1985; Angiology 22:4484–55, 1971

Subcorneal pustular dermatosis

Facial port wine stain – enlarged lip JAAD 67:6876–93, 2012

Warts, increased growth

Pruritus Pustular psoriasiform eruptions Sclerotic skin plaques Seborrheic dermatitis, worsening Vaginal ulcers Verrucous hyperplasia

Granulomatosis with polyangiitis Hematoma Infantile hemangioma (proliferating hemangioma – enlarged red lip J Eur Acad DV March 2, 2020; doi:10.1111/jdr.16331; Ped Derm 31:7547–55, 2014; Ped Derm 29:1241–26, 2012; resolved hemangioma; hemangioma beyond proliferative stage – hypertrophy of the lip, chin, and neck Ped Derm 28:949–8, 2011 Intramuscular vascular malformation Ped Derm 31:657, 2014 Kimura's disease JAAD 38:1431–75, 1998 Lymphangiectasia – macrocheilia South Med J 69:4854–86, 1976 Lymphangioma Lymphatic malformation, microcystic Ped Derm 36:9679–69, 2019 Lymphedema Pyogenic granuloma Sclerosing lymphangitis of the lip J Dermatol 17:1271–29, 1990 Superior vena cava syndrome Stat Pearls Feb 4, 2019; Emerg Med Clin NA 36:5775–84, 2018 Vascular malformation – personal observation Venous obstruction Venous lake

LITHIUM, CUTANEOUS SIDE EFFECTS Acne and acneiform eruptions Alopecia Dermatitis Erythema multiforme Exfoliative erythroderma Fixed drug eruption Folliculitis Geographic tongue Hidradenitis suppurativa Lichenoid stomatitis

 IVEDO RETICULARIS WITH OR L WITHOUT NECROSIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – autosomal recessive; mutation in cat eye syndrome chromosome candidate 1 gene; intermittent livedo reticularis, cutaneous ulcers, digital gangrene, oral aphthae, Raynaud’s phenomenon, necrosis, fever, early recurrent strokes, hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:1992–01, 2020; NEJM 380:15821–584, 2019; Ped Derm 33:6026–14, 2016; NEJM 370:9119–20, 2014; NEJM 370:9219–31, 2014 Adenosine deaminase type II deficiency – loss of function mutation in cecr1; painless leg nodules with intermittent livedo reticularis; vasculitis of small and medium arteries; cutaneous, neurologic (ischemic and hemorrhagic stroke, infarcts), peripheral and cranial neuropathy; and gastrointestinal involvement (diarrhea); livedo, subcutaneous nodules, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae Ped Derm 37:1992–01, 2020 Aicardi-Goutieres syndrome (interferonopathy) – autosomal recessive; neurodegenerative disease; mutation in three-prime repair exonuclease 1(TREX1;AGS1); mutation in sterile alpha motif domain and HD domain-containing protein1(SAMHD1;AGS5); mutation in three genes encoding for components of ribonuclease H@ subunit A endonuclease complex (AGS24–); mutation in gene for RNA-specific adenosine deaminase 1(AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1(AGS7); chilblain-like lesions; acrocyanosis; red periungual lesions; red earlobes; livedo reticularis, blueberry muffin baby; congenital encephalopathy with developmental delay; microcephaly; narrow facial features; seizures, spasticity, dystonic posturing Ped Derm 33:6026–14, 2016 Dermatomyositis – livedo reticularis and multiple ulcers J Eur Acad DV 11:485–0, 1998

Livedo Reticularis with or Without Necrosis Hypogammaglobulinemia, congenital JAAD 52:10091–019, 2005

Ergotism, chronic

Lupus erythematosus – systemic lupus erythematosus BJD 135:3553–62, 1996; livedo – of upper or lower extremities; J Rheumatol 6:2042–09, 1979; discoid lupus, tumid lupus – livedoid telangiectasias JAAD 41:2502–53, 1999 subacute cutaneous lupus erythematosus Med Clin North Am 73:10731–090, 1989; JAAD 19:19571–062, 1988; lupus vasculitis JAAD 48:3113–40, 2003

Erythromycin/lovastatin interaction JAAD 52:10091–019, 2005

Mixed connective tissue disease Rheumatoid arthritis; vasculitis JAAD 53:1912–09, 2005; JAAD 48:3113–40, 2003; BJD 147:9059–13, 2002; intravascular or intralymphatic histiocytosis in rheumatoid arthritis; red livedoid plaques BJD 152:13851–387, 2005; JAAD 50:5855–90, 2004 Scleroderma AD 119:8038–07, 1983 Sjogren’s syndrome JAAD 52:10091–019, 2005 Still’s disease JAAD 52:10091–019, 2005

CONGENITAL LIVEDO Angioma serpiginosum Capillary nevi Congenital livedo reticularis

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Gemcitabine JAAD 52:10091–019, 2005 GCSF – recombinant human GCSF; livedo reticularis, edema, with thrombotic and necrotizing panniculitis BJD 142:8348–36, 2000 Heparin-induced thrombocytopenia – livedo reticularis with necrosis (livedo racemosa) Personal observation, 2007 Heparin JAAD 52:10091–019, 2005; heparin-induced thrombocytopenia JAAD 82:7837–96, 2020 Interferon beta-1b Ped Derm 29:3333–35, 2012; JAAD 37:5535–58, 1997 Minocycline-induced p-ANCA+ cutaneous polyarteritis nodosa – vasculitis Eur J Dermatol 13:3663–68, 2003; JAAD 48:3113–40, 2003; JAAD 44:1982–06, 2001 Pentazocine injection J R Soc Med 75:9039–09, 1982 Phenylephrine-induced microvascular occlusion syndrome – livedo racemosa, acral cyanosis, and necrosis with hemorrhagic bullae AD 143:13141–317, 2007 Propylthiouracil – ANCA+ leukocytoclastic vasculitis; stellate purpura AD 142:8798–80, 2006

Cutis marmorata telangiectatica congenita JAAD 20:10981–104, 1989

Quinidine – photosensitive purpuric livedo JAAD 12:3323–36, 1985; Dermatologica 148:3713–76, 1974; AD 108:1001–01, 1973

Diffuse phlebectasia (Bockenheimer's syndrome)

Quinine

Divry-van Bogaert syndrome (corticomeningeal angiomatosis)

Soñodor (diphenhydramine and pyrithyldione) JAAD 52:10091–019, 2005

Klippel-Trenaunay-Weber syndrome Lupus erythematosus, neonatal Port wine stain with reticulate pattern JAAD 60:6696–75, 2009 Rubor – transient neonatal rubor due to vasodilatation and hyperemia, especially of the head; with cutis marmorata JAAD 60:6696–75, 2009

DEGENERATIVE

Warfarin-associated nonuremic calciphylaxis JAMADerm 1533– 093–14, 2017

EXOGENOUS CAUSES Arterial cannula, arterial embolization with hyaluronic acid – livedo reticularis of nose and face BJD 146:9289–29, 2002

Encephalitis JAAD 52:10091–019, 2005

Buprenorphine, surreptitious intra-arterial administration – livedo racemosa (necrotic livedo reticularis) AD 146:2082–09, 2010; high-dose buprenorphine injections – livedo with necrosis BJD 172:14121–414, 2015

Multiple sclerosis JAAD 52:10091–019, 2005

Carbon dioxide arteriography JAAD 52:10091–019, 2005

Paralysis – stasis

Cocaine abuse – levamisole-contaminated cocaine – retiform purpura; necrotic purpura (livedo racemosa), purpura of ears, cheeks, and nose; stellate livedo racemosa JAAD 65:7227–25, 2011; JAAD 63:5305–35, 2010; Pediatr Nephrol 13:6026–03, 1999

Brain injury JAAD 52:10091–019, 2005

Parkinson’s disease JAAD 52:10091–019, 2005 Poliomyelitis JAAD 52:10091–019, 2005

DRUG-INDUCED

Crack inhalation – acrocyanosis, necrotizing livedo reticularis (livedo racemosa), and muscle infarction Ann Int Med 108:843, 1988

Amantadine Ped Derm 29:3293–30, 2012; SKINmed 9:3203–21, 2011; BJD 149:6566–58, 2003; JAAD 125:4174–22, 1989

Endovascular devices – microemboli from hydrophilic polymer from endovascular devices – purpuric livedo racemosa JAAD 73:6666– 75, 2015

Arsphenamine JAAD 52:10091–019, 2005

Hyaluronic acid embolism JAMA Derm 149:3733–75, 2013

Axitinib (VEGF inhibitor) – purpuric livedoid vasculopathy of feet JAMADerm 152:2222–23, 2016

Levamisole-adulterated cocaine – cutaneous necrosis (livedo racemosa) associated with cocaine abuse (cocaine cut with levamisole); retiform purpura with neutropenia and vasculitis; purpura of ears, nose, and cheeks; thrombotic vasculopathy; perinuclear ANCA positivity; livedo racemosa JAAD 82:7837–96, 2020; JAAD 69:1351–42, 2013; Cutis 91:212–4, 2013;; JAAD 65:7227–25, 2011; AD 146:13201–321, 2010

Bismuth injection, intra-arterial Catecholamines JAAD 52:10091–019, 2005 Copaxone injection site reaction – personal observation Coumarin – coumarin necrosis, coumarin purple toe syndrome Thromb Haemost 78:7857–90, 1997; livedo racemosa JAAD 82:7837–96, 2020 Doxorubicin reaction – personal observation

Intra-arterial injections Nitrogen – decompression sickness JAAD 52:10091–019, 2005 Ventilator gas embolism JAAD 52:10091–019, 2005

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INFECTIONS AND INFESTATIONS

INFILTRATIVE DISEASES

Angioinvasive fungi – livedo racemosa JAAD 82:7837–96, 2020

Amyloidosis JAAD 52:10091–019, 2005

Babesiosis (Babesia microti) – mottled skin, fever, vomiting, severe anemia in 35 day old infant NEJM 370:7537–62, 2014

Intralymphatic histiocytosis – linear and serpiginous (possibly paraneoplastic, associated with Merkel cell tumor, breast cancer, lung adenocarcinoma) JAMADerm 155:9609–61, 2019; Histopathol 24:2652–68, 1994

Bacterial endocarditis – acute or subacute; acute – Staphylococcus aureus; livedo reticularis of trunk, purpuric eruption of hands; fever, confusion, thrombocytopenia, renal failure NEJM 370:6516–60, 2014 Brown recluse spider bites (Loxosceles reclusa) – ecchymosis, ischemic pallor and erythema, livedoid necrosis, eschar JAMADerm 150:12051–208, 2014; JAAD 67:3473–54, 2012

Primary and secondary intralymphatic histiocytosis – red patch of back; livedo reticularis JAAD 70:9279–33, 2014

Brucella JAAD 52:10091–019, 2005

INFLAMMATORY DISEASES

Capnocytophaga canimorsus – bacteremia with purpura fulminans NEJM 369:12381–248, 2014

Fibromyalgia JAAD 52:10091–019, 2005

COVID-19 – livedo racemosa and livedo reticularis in more severely ill patients

Pancreatitis, chronic – livedo reticularis; “Walzel’s sign” JAAD 39:10351–036, 1998 Relapsing polychondritis Medicine 80:1731–79, 2000

Coxiella burnetii JAAD 52:10091–019, 2005 Cytomegalovirus infection – livedo reticularis and perianal ulcers – CMV vasculopathy JAAD 64:12161–218, 2011

METABOLIC

Ecthyma gangrenosum – livedo racemosa JAAD 82:7837–96, 2020

Anti-thrombin III deficiency JAAD 52:10091–019, 2005

Endocarditis JAAD 52:10091–019, 2005; infective endocarditis and aortitis due to Staphylococcus aureus NEJM 370:6516–60, 2014

Calciphylaxis(vascular calcification cutaneous necrosis syndrome) (cutaneous calcinosis in end-stage renal disease) – necrotic cutaneous ulcers, livedo racemosa (livedoid necrosis), hemorrhagic patches, indurated plaques, hemorrhagic bullae JAAD 56:5695–79, 2007; (chronic renal failure and hyperparathyroidism) NEJM 378:17041–714, 2018; JAMA Derm 149:9469–49, 2013; JAMA Derm 149:1631–67, 2013; Am J Dermatopathol 33:7968–02, 2011; JAAD 58:4584–71, 2008; CIASN 3:11391–143, 2008; AD 143:1521–54, 2007; Ped Derm 23:2662–72, 2006; JAAD 40:9799– 87, 1999; JAAD 33:535–8, 1995; JAAD 33:9549–62, 1995;J Dermatol 28:273–1, 2001; Br J Plast Surg 53:2532–55, 2000; J Cutan Med Surg 2:2452–48, 1998; JAAD 33:9549–62, 1995; AD 131:786, 1995; AD 127:2252–30, 1991; Arch Int Med 136:12731– 280, 1976; acute reversible renal failure; associated with hepatitis C infection JAAD 50:S1251–28, 2004; calciphylaxis with stellate necrosis and retiform purpura unassociated with renal disease; associated with hypoalbuminemia, malignancy, systemic corticosteroid therapy, coumarin, chemotherapy, systemic inflammation, cirrhosis, protein C or S deficiency, obesity, rapid weight loss, infection AD 145:4514–58, 2009

Hepatitis C – symmetric polyarthritis with livedo reticularis JAAD 37:8178–23, 1997 Infectious mononucleosis Leprosy – Lucio’s phenomenon; livedo racemosa JAAD 82:7837– 96, 2020 Severe malaria – livedo racemosa JAAD 82:7837–96, 2020 Meningococcemia – livedo racemosa JAAD 82:7837–96, 2020; JAAD 52:10091–019, 2005 Mycobacterium tuberculosis JAAD 52:10091–019, 2005 Mycoplasma pneumoniae – cold agglutinins JAAD 52:10091–019, 2005 Necrotizing fasciitis with symmetric peripheral gangrene, pneumococcal sepsis – personal observation Parvovirus B 19 with myasthenia gravis-like syndrome AD 131:7447–45, 1995 Pneumococcal sepsis Q fever (Coxiella burnetii) JAAD 41:8428–44, 1999 Rheumatic fever Rickettsial diseases JAAD 52:10091–019, 2005 Rubella – congenital rubella syndrome – seborrhea, cutis marmorata, hyperpigmentation JAAD 46:1611–83, 2002 Septic emboli – with pseudoaneurysms due to Staph aureus following percutaneous transluminal coronary angioplasty; palpable purpura, petechiae, and livedo reticularis JAAD 82:7837–96, 2020; Cutis 66:4474–52, 2000 Staphylococcal sepsis – livedo racemosa JAAD 82:7837–96, 2020 Streptococcemia – livedo racemosa JAAD 82:7837–96, 2020; JAAD 52:10091–019, 2005 Strongyloides hyperinfection – livedo racemosa JAAD 82:7837–96, 2020 Syphilis

Cardiac failure JAAD 52:10091–019, 2005 Catastrophic anti-phospholipid antibody syndrome NEJM 370:6516–60, 2014 Central nervous system disease – generalized livedo reticularis – personal observation Cholesterol emboli – livedo racemosa JAAD 82:7837–96, 2020 Cold agglutininemia JAAD 82:7837–96, 2020 Cretinism – coarse facial features, lethargy, macroglossia, cold dry skin, livedo, umbilical hernia, poor muscle tone, coarse scalp hair, synophrys, no pubic or axillary hair at puberty Cryofibrinogenemia JAAD 82:7837–96, 2020; AD 144:4054–10, 2008; Am J Med 116:3323–37, 2004 Cryoglobulinemia JAAD 48:3113–40, 2003; type I cryoglobulinemia in multiple myeloma – acral cyanosis, Raynaud’s phenomenon; livedoid necrosis of arms, ears JAAD 82:7837–96, 2020;

Varicella – livedo reticularis as the only manifestation

JAMADerm 151:6596–60, 2015; type I cryoglobulinemia in Waldenstrom’s macroglobulinemia or myeloma Medicine (Balt) 92:616–8, 2013; Am J Med 57:7757–88, 1974

Viral syndromes JAAD 52:10091–019, 2005

Cushing's syndrome JAAD 52:10091–019, 2005

Typhus JAAD 52:10091–019, 2005

Livedo Reticularis with or Without Necrosis

613

Diabetes mellitus – peripheral neuropathy JAAD 52:10091–019, 2005

Red blood cell occlusion – sickle cell disease, thalassemia -livedo racemosa JAAD 82:7837–96, 2020

Disseminated intravascular coagulation, including symmetric peripheral gangrene JAAD 52:10091–019, 2005

Renal disease, chronic – calciphylaxis

Essential thrombocythemia JAAD 82:7837–96, 2020

Thrombocytopathy JAAD 52:10091–019, 2005

Factor V Leiden – livedo racemosa JAAD 82:7837–96, 2020

Thrombotic thrombocytopenic purpura JAAD 82:7837–96, 2020; NEJM 370:6516–60, 2014; JAAD 52:10091–019, 2005

Hemolytic uremic syndrome – livedo racemosa JAAD 82:7837–96, 2020; JAAD 52:10091–019, 2005 Hereditary spherocytosis – livedo racemosa JAAD 82:7837–96, 2020 Homocystinuria – cystathionine-beta synthase deficiency – livedo racemosa JAAD 82:7837–96, 2020; JAAD 40:2792–81, 1999 Hypercalcemia JAAD 52:10091–019, 2005 Hypercoagulable state – livedo racemosa JAAD 82:7837–96, 2020 Hyperparathyroidism with vascular calcification Hyperviscosity JAAD 60:12–0, 2009 Hypothyroidism JAAD 52:10091–019, 2005 Methylenetetrahydrofolate reductase deficiency – nonuremic calciphylaxis; livedoid necrosis JAAD 69:3243–26, 2013; AD 147:4504–53, 2011 Oxalosis (primary oxalosis) – autosomal recessive; livedo reticularis, acrocyanosis, peripheral gangrene, ulcerations, sclerodermoid changes (woody induration of extremities), eschar of hand (calcium oxalate); acral and/or facial papules or nodules; end-stage renal disease; primary hyperoxalosis – deficiency of alanine-glyoxylate aminotransferase; primary hyperoxalosis – deficiency of D-glycerate dehydrogenase/glyoxylate reductase NEJM 369:6496–58, 2014; AD 147:12771–282, 2011

Symmetric peripheral gangrene – personal observation

NEOPLASTIC Aortic tumors – aortic angiosarcoma with cutaneous metastases JAAD 43:9309–33, 2000; primary aortic tumors Oncology 39:1671– 72, 1982 Congenital smooth muscle hamartoma with livedo appearance – resembles cutis marmorata telangiectatica congenita with fibrotic appearance Ped Derm 37:2042–06, 2020 Cutaneous radiation-associated angiosarcoma of the breast – livedoid violaceous plaques with nodules of the breast JAMA Derm 149:9739–74, 2013 Atrial myxoma BJD 147:3793–82, 2002; Cutis 62:2752–80, 1998; JAAD 32:8818–83, 1995; JAAD 25:1101–11, 1991 Gamma heavy chain disease JAAD 23:9889–91, 1990 Inflammatory breast carcinoma JAAD 52:10091–019, 2005 Leukemia – chronic myelogenous leukemia with leukostasis; acral livedo AD 123:9219–24, 1987; acute lymphocytic leukemia JAAD 52:10091–019, 2005; leukemic vasculitis – livedo racemosa JAAD 82:7837–96, 2020

Paroxysmal nocturnal hemoglobinuria – livedo racemosa, painful ecchymoses, purpura, hemorrhagic bullae, ulcers; mutation PIGA gene which encodes glycosylphosphatidylinisitol-anchored proteins (decrease in GPI proteins in cell membranes); complement-induced intravascular hemolysis; increased thrombosis JAAD 82:7837–96, 2020; BJD 171:9089–10, 2014

Lymphomas – cutaneous T-cell lymphoma JAAD 52:10091–019, 2005; intravascular large cell lymphoma – white blood cell occlusion – livedo racemosa JAAD 82:7837–96, 2020; JAAD 39:3183– 21, 1998

Pellagra JAAD 52:10091–019, 2005

Nevus oligemicus AD 117:1111–13, 1981

Pernicious anemia JAAD 52:10091–019, 2005

Pheochromocytoma JAAD 52:10091–019, 2005

Platelet diathesis – livedo racemosa JAAD 82:7837–96, 2020

Polycythemia vera JAAD 26:2642–65, 1992

Pregnancy – cutis marmorata of legs

Renal cell carcinoma JAAD 52:10091–019, 2005

Primary oxalosis (primary hyperoxaluria) – type I – alanine glyoxylate aminotransferase (transaminase) deficiency; chromosome 2q363–7; type II (rare) – D-glyceric acid dehydrogenase deficiency JAAD 49:7257–28, 2003; JAAD 46:S161–8, 2002; AD 137:9579–62, 2001; JAAD 22:9529–56, 1990; AD 131:8218–23, 1995; AD 125:3803–83, 1989; livedo reticularis, ulcers, and peripheral gangrene AD 136:12721–274, 2000

Essential thrombocythemia JAAD 24:596–3, 1991;

Primary hyperoxaluria – livedo reticularis AD 147:13021–305, 2011; Clin Exper Dermatol 16:3673–70, 1991; peripheral (digital) ischemia Hemodial Int 13:2662–70, 2009; AD 136:12721–274, 2000; ulcers AD 131:8218–23, 1995  Primary hyperoxaluria type I – decreased peroxisomal, liverspecific alanine glyoxylate aminotransferase BJD 169:2272–30, 2013  Primary hyperoxaluria type II – glyoxylate/hydroxypyruvate reductase; GRHPR gene mutation BJD 169:2272–30, 2013  Primary hyperoxaluria type III – decreased 4-hydroxy 2-oxyglutarate aldolase BJD 169:2272–30, 2013

NORMAL

Multiple myeloma with paraproteins and crystaloglobulins JAAD 52:10091–019, 2005

Br J Haematol 36:5535–64, 1977; AD 87:3023–05, 1963 Waldenstrom’s macroglobulinemia AD 134:11271–131, 1998; cryoglobulin-­associated livedo reticularis JAAD 45:S2022–06, 2001

Cutis marmorata – physiologic JAAD 52:10091–019, 2005 Physiologic

PARANEOPLASTIC DISEASES Type I cryoglobulinemia – with myeloma; livedo racemosa (necrotizing livedo reticularis) J Drugs Dermatol 13:4984–99, 2014

Protein S and C deficiency – livedo racemosa JAAD 82:7837–96, 2020; JAAD 52:10091–019, 2005

PHOTODERMATOSES

Prothrombin III mutation – livedo racemosa JAAD 82:7837–96, 2020

Livedo reticularis, photosensitive AD 108:1001–01, 1973

614

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

PRIMARY CUTANEOUS DISEASES Physiologic cutis marmorata – personal observation

ears, hair whorls of trunk, cutis marmorata, single palmar crease, physical and mental retardation JAAD 52:10091–019, 2005; Am J Med Genet 47:9599–64, 1993; marbling around the eyes and nose

Lichen planus

Corticomeningeal angiomatosis Eur Neurol 9:2022–15, 1973

Livedo reticularis, primary JAAD 52:10091–019, 2005

DADA2 (deficiency of adenosine deaminase 2) – autosomal recessive; recurrent fevers, early-onset stroke, livedo racemosa, polyarteritis nodosa, hepatosplenomegaly; mutation in CECR1 JAAD 75:4494–53, 2016

Livedo reticularis of the breast – personal observation Nevus anemicus Non-episodic angioedema with eosinophilia – erythema, livedo reticularis, edema of legs, urticaria Cutis 93:333–7, 2014 Psoriasis Cutis 39:4294–32, 1987 Symmetrical lividity of the soles BJD 37:1231–25, 1925

SYNDROMES Adams-Oliver syndrome – autosomal dominant; terminal transverse limb anomalies, aplasia cutis congenita, cutis marmorata telangiectatica congenita, severe growth retardation, aplasia cutis congenita of knee, short palpebral fissures, dilated scalp veins, simple pinnae, skin tags on toes, hemangioma, undescended testes, supernumerary nipples, hypoplastic optic nerve, congenital heart defects Ped Derm 24:6516–53, 2007; Ped Derm 22:2062–09, 2005 Adenosine deaminase 2(ADA2) mutation – mutation in CECR1; intermittent fevers, early-onset lacunar strokes, livedoid eruption, hepatosplenomegaly, systemic vasculopathy NEJM 370:9119–20, 2014 Aicardi-Goutieres syndrome – autosomal recessive; chilblains, acrocyanosis, livedo reticularis, puffy hands and feet; distal tapering of fingertips; blueberry muffin baby; congenital progressive encephalopathy, basal ganglia intracranial calcification with enlarged ventricles; increased interferon alpha in blood and cerebrospinal fluid and CSF lymphocytosis Ped Derm 26:4324–35, 2009; JAAD 61:7277–28, 2009; Ped Derm 26:4324–35, 2009; Am J Hum Genet 81:7137–25, 2007; Eur J Paediatr Neurol 69(Suppl A):A1–A7, 2002; Ann Neurol 44:9009–07, 1998 Anti-cardiolipin antibody syndrome – personal observation Antiphospholipid antibody syndrome JAAD 82:7837–96, 2020; BJD 157:3893–92, 2007; NEJM 346:7527–63, 2002; Semin Arthritis Rheum 31:1271–32, 2001; JAAD 36:1491–68, 1997; JAAD 36:9709–82, 1997; BJD 120:4194–29, 1989; IgG-1 antibodies to beta-2 glycoprotein 1 Am J Med 101:4722–81, 1996; acral livedo and necrosis AD 147:1641–67, 2011; catastrophic anti-phospholipid antibody syndrome – personal observation BASCULE – Bier anemic spots, cyanosis, with urticarial-like eruption BJD 175:2182–20, 2016

Down's syndrome JAAD 52:10091–019, 2005 Hypereosinophilic syndrome – livedo reticularis with superficial venous thromboses AD 142:16061–610, 2006 Hypotrichosis-lymphedema-telangiectasia-renal failure syndrome – diffuse reticulated capillary malformation, hypertensive emergency with transient ischemic attack, dilatation or aortic root, pleural effusions, acute kidney injury, thin facies with telangiectasias of cheeks, livedo reticularis of trunk and extremities; mutation in SOX18 gene Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016 Macrocephaly with cutis marmorata, hemangioma, and syndactyly syndrome – macrocephaly, facial hemihypertrophy, cutis marmorata telangiectatica congenita, syndactyly, joint laxity, thick subcutaneous tissue, developmental delay, short stature, hydrocephalus, internal arteriovenous malformations, hemangioma of philtrum of upper lip, syndactyly of toes, hyperelastic skin capillary and cavernous hemangiomas Ped Derm 16:2352–37, 1999; Clin Dysmorphol 6:2913–02, 1997 Neurofibromatosis type I – vasculopathy; acral necrosis, livedoid painful ulcerations BJD 172:2532–56, 2015; Pediatrics 100:3953– 97, 1997; JAAD 51:6566–59, 2004; neurofibromatosis type I – plexiform neurofibroma with pressure-induced arterial occlusion and livedo racemosa JAAD 50:S1071–09, 2004 Nicolau syndrome – following intramuscular injection (of bismuth, diclofenac, ibuprofen), intra-arterial, acute ischemia, severe pain, livedo, necrosis of skin and muscle, dendritic extension, ulcer, necrotic eschar, atrophic scar BJD 150:3853–87, 2004; J Eur Acad Dermatol 15:5855–88, 2001; Ped Derm 12:1871–90, 1995; Ann Int Med 117:1058, 1992; livedoid aseptic necrosis after injections JAAD 54:S2412–42, 2006 Phakomatosis cesiomarmorata – Mongolian spot and cutis marmorata telangiectatica congenita AD 141:3853–88, 2005 POEMS syndrome – livedo racemosa (livedo reticularis with necrosis) AD 146:6156–23, 2010; JAAD 37:8879–20, 1997; JAAD 40:8088–12, 1999; JAAD 19:9799–82, 1988 Reflex sympathetic dystrophy JAAD 52:10091–019, 2005 Relapsing polychondritis Clin Exp Rheumatol 20:899–1, 2002

Carcinoid syndrome JAAD 52:10091–019, 2005

Riley-Day syndrome (familial dysautonomia) – mottling

Cardio-facio-cutaneous syndrome

Rothmund-Thomson syndrome

Cockayne syndrome – xerosis with rough, dry skin, anhidrosis, erythema of hands, hypogonadism; autosomal recessive; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, cyanotic livedo reticularis, disproportionately large hands, feet, and ears, dental caries, sensorineural hearing loss, ocular defects including retinal degeneration, demyelination JAAD 75:8738–82, 2016; JAMA Derm 149:14141– 418, 2013; Ped Derm 20:5385–40, 2003; Am J Hum Genet 50:6776–89, 1992; J Med Genet 18:2882–93, 1981; bird-headed dwarfism

SAVI – (STING (stimulator of interferon genes)-associated vasculopathy) – progressive digital necrosis, swelling of fingers, amputation of several digits, violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of arms and legs JAAD 74:1861–89, 2016

Cornelia de Lange (Brachmann-de Lange) syndrome – generalized hypertrichosis, confluent eyebrows, low hairline, hairy forehead and

Sharp’s syndrome JAAD 52:10091–019, 2005 Sneddon's syndrome – livedo reticularis associated with arterial disease of cerebral, coronary, renal, and peripheral vessels; hypertension and neurologic signs and symptoms; cerebrovascular episodes; dementia; antiphospholipid antibodies and lupus anticoagulant often but not invariably present; thrombocytopenia JAAD 61:10761–078, 2009; Cutis 67:2112–14, 2001; BJD

Livedo Reticularis with or Without Necrosis

615

142:3743–76, 2000; Sem Derm 14:1661–72, 1995; JAAD 22:6336– 39, 1990; Int J Dermatol 29:454–9, 1990; BJD 77:1801–85, 1965;

Anti-thrombin III deficiency – livedo racemosa JAAD 82:7837–96, 2020

livedo racemosa generalisata JAAD 22:6339–, 1990; cutaneous thrombosis, cerebrovascular thrombosis, and lupus anticoagulant Int J Dermatol 29:454–9, 1990; associated with neuropathic pain of the head and feet SkinMed 11:2512–52, 2013; livedo racemosa with leg ulcers JAMADerm 152:7267–27, 2016

Arteriosclerosis

Trisomy 18 JAAD 52:10091–019, 2005

TOXINS Acrodynia (pink disease) – reticulate erythema of hands; mercury poisoning

TRAUMA Air emboli – livedo racemosa JAAD 82:7837–96, 2020 Arterial line – personal observation Caisson’s disease – personal observation Catheterization with livedo racemosa from emboli – personal observation Chilblains Mayo Clin Proc 89:2072–15, 2014 Cold injury – cutis marmorata Compressed air illness (decompression sickness) (Caisson's disease) Erythema ab igne – sitting in front of stove BJD 110:3693–75, 1984; recliner chairs JAAD 34:5165–17, 1996; AD 126:3863–89, 1990; hospital heating blanket Cutis 66:1361–38, 2000; laptop computer JAAD 50:9739–74, 2004; laptop computer on breast Cutis 87:1751– 76, 2011; hot baths Acta DV 82:4784–79, 2002; hot popcorn J Dermatol 29:1721–73, 2002; car heater Cutis 59:818–2, 1997; electric heater Dermatol Online J 9:18, 2003; heating devices for cancer pain Pain 87:1071–08, 2000 Frostbite Ice pack dermatosis – red plaque, retiform purpura with purpuric papules and ulcers JAMA Derm 149:13141–318, 2013 Immersion foot due to ice, cold water, and fans – acral cyanosis, mottled coloration, marked edema of feet, maceration, bullae, erosions, painful ulcers, pain JAAD 69:1691–71, 2013 Infrared radiation – erythema ab igne Intra-arterial cannula Intravenous drug abuse – intra-arterial buprenorphine tablets injected within brachial artery BJD 150:11–0, 2004 Midline catheter insertion JAAD 52:10091–019, 2005

Atrophie blanche – livedo with summer (winter)ulcerations JAAD 8:7927–98, 1983; AD 119:9639–69, 1983 Cholesterol emboli JAAD 55:7867–93, 2006; BJD 146:11071–108, 2002; BJD 146:5115–17, 2002; BJD 146:5115–17, 2002;; Medicine 74:3503–58, 1995; Angiology 38:7697–84, 1987; AD 112:11941–198, 1986; JAAD 13:2352–42, 1985; facial livedo racemosa – cholesterol emboli from carotid arteries JAAD 64:12031–205, 2011; ulcerated plaques of buttocks with livedo reticularis JAMADerm 150:9039–05, 2014 Coarctation of the aorta – cutaneous mottling of arm BJD 148:10661–068, 2003 Congenital fibromuscular dysplasia BJD 163:13621–364, 2010 Congenital heart disease – personal observation Congenital plaque-type glomuvenous malformations – glomulin gene on 1p21; loss of function mutation; atrophic at birth; livedoid plaques, blue plaques, vascular nodules, red patches, cerebriform, targetoid AD 142:8928–96, 2006 Congestive heart failure – stasis Cutaneous polyarteritis nodosa – angioedema; livedo reticularis, lower leg ulcers JAMADerm 150:8808–84, 2014; ankle ulcer with livedo reticularis Ped Derm 36:9329–35, 2019 Cutis marmorata telangiectatica congenital – livedo reticularis with hemiatrophy BJD 170:6816–86, 2014 Degos’ disease – retiform purpura AD 143:13141–317, 2007; Adv Dermatol 15:1531–82, 1999 Diffuse dermal angiomatosis – livedo reticularis with necrosis; associated with atherosclerosis AD 146:6846–85, 2010; AD 138:4564–58, 2003; due to arteriovenous fistula J Cutan Pathol 26:1591–64, 1999; associated with macromastia – livedo reticularis on undersides of breasts AD 144:6936–94, 2008; diffuse dermal angiomatosis of the breast Gland Surg 4:5545–60, 2015; JAAD 71:12121–217, 2014; Int J Derm 53:4454–49, 2014; AD 142:3433– 47, 2006; JAAD 45:4624–65, 2001 Disseminated intravascular coagulation – livedo racemosa JAAD 82:7837–96, 2020 Eosinophilic granulomatosis with polyangiitis (Churg-Strauss disease) Medicine 78:263–7, 1999; JAAD 37:1992–2003, 1997; BJD 127:1992–04, 1992; presenting as purpura fulminans Clin Exp Dermatol 29:3903–92, 2004 Factor XII deficiency – livedo with ulceration BJD 143:8978–99, 2000 Fat emboli JAAD 52:10091–019, 2005 Granulomatosis with polyangiitis – breast necrosis, livedo reticularis, arthralgias Rev Med Brux 33:1121–15, 2012

VASCULAR

Hypertensive ulcer (Martorell’s ulcer) – very painful ulcer of lower lateral leg with livedo at edges Phlebology 3:1391–42, 1988

Acquired capillary malformation – reticulated erythema of distal thigh; PIK3CA (overgrowth mutation) Ped Derm 37:2462–47, 2020

Idiopathic systemic capillary leak syndrome – skin-colored or red papules of face, neck, abdomen, upper back, elbows, and hands; purpuric macules of lateral fingers, infiltrative edema of hands with sclerodermoid appearance, livedo reticularis of lower extremities; photodistributed eruption of the face, neck, and arms Dermatology 209:2912–95, 2004

Acral necrotic livedo reticularis – surgical acrylic cement embolus following vertebroplasty BJD 156:3823–83, 2007 Adenosine deaminase 2(ADA2) mutation – mutation in CECR1; intermittent fevers, early-onset lacunar strokes, livedoid eruption, hepatosplenomegaly, systemic vasculopathy NEJM 370:9119–20, 2014 ANCA-positive vasculitis – livedo racemosa JAAD 82:7837–96, 2020 Angioma serpiginosum – retiform red patches of leg AD 147:878, 2011

IgA vasculitis – livedo racemosa JAAD 82:7837–96, 2020 Intramural thrombus – embolus Kaposiform hemangioendothelioma with Kasabach-Merritt syndrome – livedoid enlarging bruise of back JAMA Derm 149:13371–338, 2013; AJDC 59:10631–070, 1940

616

THE

CLINICIAN’S

GUIDE

TO

DERMATOLOGIC

DIFFERENTIAL

Klippel-Trenaunay-Weber syndrome Livedo racemosa Livedo reticularis – acquired idiopathic Livedo reticularis with winter ulceration Livedoid purpura JAMADerm 151:6596–60, 2015   Lucio’s phenomenon   Purpura fulminans   Anti-phospholipid antibodies   Cholesterol emboli  Levamisole  Perniosis Livedoid vasculopathy (atrophie blanche en plaque; atrophie blanche with summer ulceration) – painful purpuric papules and plaques; leg and ankle ulcers; atrophic white scars; livedo reticularis JAAD 69:10331–042, 2013 Lymphatic net-like malformation – Blaschko-esque livedo reticularislike lesions of buttocks, thighs, and upper back; superficial lymphatic malformation high in dermis Cases of the Year, Pre-AAD Pediatric Dermatology Meeting Lymphocytic thrombophilic arteritis – painless non-ulcerating livedo reticularis, reticulated hyperpigmentation, red nodules AD 144:11751–182, 2008 Malignant angioendotheliomatosis (angiocentric lymphoma) – scalp; livedoid red plaque of thigh with woody induration JAAD 18:4074– 12, 1988 Marantic endocarditis – livedo racemosa JAAD 82:7837–96, 2020 Moyamoya disease – narrowing or occlusion of supraclinoid portion of the internal carotid artery and stems of anterior and middle cerebral arteries Ped Derm 20:1241–27, 2003 Neurologic syndromes – cerebral vascular accidents, transient ischemic attacks Parkes-Weber syndrome Peripheral vascular disease  Vessel wall disease – arteriosclerotic, hyperparathyroidism, arteritis (PAN, rheumatoid arthritis, LE, dermatomyositis, lymphoma, syphilis, tuberculosis, pancreatitis) JAAD 18:10031– 019, 1988  Platelet plugging – retiform purpura AD 143:13141–317, 2007; Adv Dermatol 15:1531–82, 1999 Polyarteritis nodosa – palpable purpura, livedo, nodules, urticaria, skin necrosis with ulcers BJD 159:6156–20, 2008; JAAD 48:3113– 40, 2003; petechiae or gross hemorrhage JAAD 31:5615–66, 1994; cutaneous infarcts presenting as purpuric plaques; microscopic polyarteritis nodosa (polyangiitis) – arthralgias, leg ulcers, fever, livedo, nodules, urticaria, palpable purpura, petechiae, ecchymoses, acral bullae, plantar red plaque BJD 159:6156–20, 2008; JAAD 57:8408–48, 2007; Eur J Dermatol 14:2552–58, 2004; microscopic polyarteritis nodosa – hemorrhagic papules (palpable purpura) JAAD 48:3113–40, 2003; AD 128:12231–228, 1992; oral purpura Oral Surg 56:5976–01, 1983; cutaneous (livedo with nodules) – purpura; painful or asymptomatic red or skin-colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk BJD 146:6946–99, 2002; splinter hemorrhages; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2(CECR1) with decreased IgA and IgM (B-cell immunodeficiency) JAMADerm 151:12301–234, 2015; NEJM 370:9219–31, 2014

DIAGNOSIS,

VOLUME

1

Port wine stain (nevus flammeus) with reticulate pattern (true capillary-­venular malformations of the superficial vascular plexus) JAAD 60:6696–75, 2009 Post-reperfusion syndrome – massive edema of muscles; may lead to amputation; peripheral cyanosis, livedo reticularis, edema of foot; myocardial injury, renal failure Int Wound J March 3, 2014; Semin Vasc Surg 22:525–7, 2009; Plast Reconstr Surg 117:10241–033, 2006 Primary pulmonary hypertension Purpura fulminans Raynaud’s disease and phenomenon Reactive glomeruloid angioendotheliomatosis – livedo reticularis with hemorrhagic ulcers of distal extremities JAAD 77:11451–158, 2017 Sickle cell anemia AD 143:13141–317, 2007; Adv Dermatol 15:1531–82, 1999 Sturge-Weber syndrome Symmetric peripheral gangrene Thromboangiitis obliterans (Buerger’s disease) Am J Med Sci 136:5675–80, 1908 Tufted angioma – reticulated erythematous patch Ped Derm 31:1231–24, 2014 Tumor emboli Vascular malformation with overlying slow flow Vasculitis (adopted from Current Prob Derm, Vol V, No.2, 1993)   Small vessel vasculitis    Circulating immune complexes   Collagen vascular disease – SLE, rheumatoid arthritis, dermatomyositis, Sjogren's syndrome, scleroderma Cutis 39:4294–32, 1987   Drug-induced vasculitis    Erythema elevatum diutinum    Familial Mediterranean fever    Henoch-Schonlein purpura; HSP of adults AD 125:535–6, 1989   Livedoid vasculitis – livedo with summer ulcerations JAAD 51:5745–79, 2004; livedoid purpura – septic vasculitis secondary to catheterization and pseudoaneurysm of femoral artery AD 142:9369–38, 2006; methylenetetrahydrofolate reductase (MTHFR) polymorphisms – thrombophilia and vasculopathy; livedo vasculopathy and MTHFR polymorphisms BJD 155:8508–52, 2006; associated with plasminogen activator inhibitor-1 promoter homozygosity AD 147:12241– 225, 2011   Mixed cryoglobulinemia   Organ transplant vasculitis   Paraneoplastic vasculitis   Serum sickness    Transplacental transient vasculitis JAAD 52:10091–019, 2005    Vasculitis of C2 deficiency    Vasculitis associated with cystic fibrosis    Vasculitis associated with subacute bacterial endocarditis  Small vessel lymphocytic vasculitis with winter or summer ulcerations    Small and medium-sized vessel vasculitis   Eosinophilic granulomatosis with polyangiitis JAAD 47:2092– 16, 2002   Dermatomyositis   Lupus erythematosus   Lymphomatoid granulomatosis   Lymphomas

Liver Disease, Cutaneous Manifestations and Hepatic Abnormalities of Skin Disease

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  Microscopic polyangiitis (polyarteritis nodosa) – livedo reticularis with surrounding erythema; acrocyanosis, ulcers, papules JAAD 57:8408–48, 2007; JAAD 52:10091–019, 2005    Necrotizing sarcoid granulomatosis   Nodular vasculitis JAAD 52:10091–019, 2005   Pancreatitis   Polyarteritis nodosa – nodules along the course of superficial arteries around knee, anterior lower leg and dorsum of foot JAAD 53:7247–28;JAAD 48:3113–40, 2003; JAAD 31:5615–66, 1994; Ann Rheum Dis 54:1341–36, 1995; Ann Int Med 89:666–76, 1978; infantile systemic – red patch heralding cutaneous infarction J Pediatr 120:2062–09, 1992   Cutaneous polyarteritis nodosa (livedo with nodules) – arthritis; arthralgias; painful or asymptomatic red or skin-colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk; leg ulcers, atrophie blanche-like lesions; reticulate hyperpigmentation JAAD 65:4424–43, 2011; JAAD 63:6026–06, 2010; JAAD 57:8408–48, 2007; BJD 146:6946– 99, 2002; anti-­phosphatidylserine-­prothrombin complex JAAD 63:6026–06, 2010; cutaneous polyarteritis nodosa – fever, muscle weakness and myalgia, and livedo with necrosis (livedo racemosa) BJD 171:2012–02, 2014; livedoid red brown patches JAMADerm 151:5495–50, 2015; JAAD 52:10091–019, 2005; BJD 146:6946–99, 2002; Ped Derm 15:1031–07, 1998; JAAD 31:5615–66,1994; cutaneous associated with Crohn’s disease Dis Colon Rectum 23:2582–62, 1980   Rheumatoid arteritis   Syphilis   Tuberculosis    Vasculitis of collagen vascular diseases    Granulomatosis with polyangiitis   Large vessel vasculitis    Giant cell arteritis    Takayasu's arteritis   Infectious vasculitis    Bacterial, including meningococcemia, Vibrio vulnificus, etc.    Fungal- including cryptococcosis, aspergillosis   Mycobacterial   Mycoplasmal   Protozoal

systemic vasculopathy; loss of function mutations in CECR1 NEJM 370:9119–20, 2014

Rickettsial   Septic emboli JAAD 52:10091–019, 2005    Spirochetal – syphilis, borrelial    Viral – cytomegalovirus AD 116:11741–176, 1980   Thrombotic vasculitis   Antiphospholipid antibodies    Anti-thrombin III deficiency    Caisson's disease – intravascular occlusion    Cardiac failure – intravascular obstruction   Cryofibrinogenemia   Cryoglobulinemia    Emboli -intravascular occlusion    Hyperviscosity – intravascular occlusion    Hypercoagulable states (DIC)   Macroglobulinemia    Paralysis – intravascular obstruction    Protein C or S deficiency   Sneddon's syndrome    Stasis – intravascular obstruction   Thrombocytosis

Dermatomyositis – MDA-5+, steatosis, hepatocellular ballooning Rheumatol Int 39:9019–09, 2019

Thrombotic vasculopathy – personal observation Vascular malformation – personal observation Vasculopathy associated with mutations in ADA2 – syndrome of livedoid rash, intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, hepatosplenomegaly, and

Venous gangrene Venous malformation JAAD 56:3533–70, 2007 Venous thrombosis, deep JAAD 52:10091–019, 2005

 IVER DISEASE, CUTANEOUS L MANIFESTATIONS AND HEPATIC ABNORMALITIES OF SKIN DISEASE  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – loss of function mutation in cat eye syndrome chromosome candidate 1 gene (CECR1); painless leg nodules with intermittent livedo reticularis, Raynaud’s phenomenon, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae; vasculitis of small and medium arteries with necrosis, fever, early recurrent ischemic and hemorrhagic strokes, peripheral and cranial neuropathy, and gastrointestinal involvement (diarrhea); hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:1992–01, 2020; NEJM 380:15821–584, 2019; JAAD 75:4494–53, 2016; Ped Derm 33:6026–14, 2016; NEJM 370:9119– 20, 2014; NEJM 370:9219–31, 2014 Autoimmune polyendocrinopathy, candidiasis, and ectodermal dysplasia (APECED) – autosomal recessive, hypoparathyroidism, Addison’s disease, chronic mucocutaneous candidiasis; autoimmune hepatitis, vitiligo, alopecia areata; autoantibodies to IL-17A, 17F, IL-22(Th 17 cytokines; mutation in AIRE JAAD 73:2552–64, 2015 Autoimmune-related granulomatous dermatitis – confluent widespread red plaques; annular red plaques; autoimmune thyroid disease; autoimmune hepatitis Case Rep Dermatol Med 2013; Case Rep Dermatol 4:808–4, 2012

Gain of function STAT1 mutations – chronic mucocutaneous candidiasis; onychodystrophy, generalized dermatophytosis; disseminated coccidioidomycosis, histoplasmosis, sinopulmonary infections, herpes simplex infections; endocrine, dental, gastrointestinal disease; diabetes mellitus, hypothyroidism, autoimmune hepatitis, cerebral aneurysms, oral and esophageal squamous cell carcinomas; increased levels of interferon results in decreased IL-17A and IL-22 JAAD 73:2552–64, 2015 Graft vs. host disease, chronic – ripply skin overlying deep sclerodermoid changes JAAD 66:5155–32, 2012; AD 138:9249–34, 2002; leg ulcers H syndrome (histiocytosis-lymphadenopathy plus syndrome) – autosomal recessive; hyperpigmented hypertrichotic plaques; hepatosplenomegaly; heart anomalies including atrial septal defect, ventricular septal defect, mitral valve prolapse, cardiomegaly, varicose veins; dilated scleral vessels, facial telangiectasias, exophthalmos, gynecomastia, scrotal masses, flexion contractures of toes and PIP joints; sensorineural hearing loss; hypogonadism; short stature; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing knees and buttock; mutation in SLC29A3 gene (equilibrative nucleoside ­transporter) Ped Derm 37:3333–36, 2020; Ped Derm 33:6026–14, 2016; JAAD 59:798–5, 2008

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IgG4 –related disease – hepatic inflammatory pseudotumor clin J Gastroenterol 10:576–2, 2017; sclerosing cholangitis Semin Diagn Pathol 36:4234–33, 2019; autoimmune hepatitis Clin Exp Dermatol 39:4794–83, 2014; sclerosing erythematous nodules of the scalp G Ital DV 151:2962–99, 2016 Lupus erythematosus, neonatal – liver pathology resembles idiopathic neonatal giant cell hepatitis Scand J Immunol 72:2232–25, 2010 Primary biliary cholangitis – Sjogren’s syndrome, systemic sclerosis, thyroid disease (Grave’s disease, Hashimoto’s thyroiditis), vitiligo Gut Liver 11:7717–80, 2017 Sjogren’s syndrome – association with hepatitis C A Clinician’s Pearls and Myths in Rheumatology pp.1071–30; ed John Stone; Springer 2009 Still’s disease, adult onset – leukocytosis with neutrophilia, increase CRP, ESR, ferritin; liver function abnormalities, hepatosplenomegaly, mild and transient, fever, sore throat, evanescent salmon-pink macular or morbilliform rash, arthritis, lymphadenopathy; complicated by hemophagocytic lymphohistiocytosis (HLH) (macrophage activation syndrome) Semin Arth Rheum 45:7117–16, 2016 Tumor necrosis factor (TNF) receptor 1-associated periodic fever syndromes (TRAPS) (same as familial Hibernian fever, autosomal dominant periodic fever with amyloidosis, and benign autosomal dominant familial periodic fever) – painful erythematous patches, tender red plaques, fever for 72–1 days, annular, serpiginous, polycyclic, reticulated, and migratory patches and plaques (migrating from proximal to distal), urticaria-like lesions, purpuric lesions resembling Henoch-Schonlein purpura; lesions resolving with ecchymoses, conjunctivitis, periorbital edema, localized myalgia which may be migratory resulting in muscle stiffness, arthralgia, abdominal pain, headache; Irish and Scottish predominance; upper extremities most commonly involved; skin lesions and myalgias move proximal to distal; renal and hepatic involvement; mutation in TNFRSF1A – gene encoding 55kDa TNF receptor JAAD 68:8348– 53, 2013; AD 144:3924–02, 2008; AD 136:14871–494, 2000

CONGENITAL LESIONS Biliary atresia, congenital – multiple xanthomas Ped Derm 25:4034– 04, 2008

INFECTIONS AND INFESTATIONS Acanthamoeba – disseminated in liver transplant recipient Transpl Infect Dis 12:5295–37, 2010 Amebiasis (Entamoeba histolytica)  Painful ulcerated nodules with undermined edges and thick central crust Anaplasmosis (human granulocytic anaplasmosis) – tick-borne; fever, headache, cervical lymphadenopathy, pulmonary infiltrates; transaminitis; macular eruption sparing the face Microbes Infect 17:8298–33, 2015; NEJM 371:3583–66, 2014; Clin Microbiol Infect 8:7637–72, 2002 Babesiosis (Babesia divergens) – vector (Ixodes ricinus tick) – fever, elevated liver function tests, thrombocytopenia NEJM 371:3583–66, 2014 Bacillary angiomatosis (Bartonella henselae) – dome-shaped red or purple papules or nodules mimicking Kaposi’s sarcoma; fever anemia, elevated alkaline phosphatase, lymphadenopathy Stat Pearls April 23, 2020; Medicine 91:1111–21, 2012   Peliosis hepatis Chikungunya fever(Chikungunya virus) – Africa, Middle East, Europe, India, Southeast Asia; fever, arthralgias, morbilliform eruption; polyarthritis and tenosynovitis; hepatitis, myocarditis, hemorrhage, meningitis, encephalitis; palpebral edema; purpuric butterfly eruption of face; necrosis of skin of nose Clin Inf Dis 62:788–1, 2016 Chronic active Epstein-Barr virus – vulvitis, hemorrhagic cheilitis, necrotic ulcers, periorbital erythema and edema, maxillary sinusitis, hepatosplenomegaly BJD 173:12661–270, 2015 Cystic echinococcosis – skin fistulae, acute and chronic urticarial, generalized pruritus, elevated IgE Am J Trop Med Hyg 95:2572–59, 2016 Fascioliasis (Fasciola hepatica, F. gigantica) – liver fluke; urticarial, jaundice, diarrhea, serpiginous tracts, subcutaneous nodules JAAD 73:9299–44, 2015 Gianotti-Crosti syndrome (papular acrodermatitis of childhood) – hepatitis B Nikon Shokakibyo Gakkai Zasshi 110:16571–662, 2013 Glanders – chronic abscesses Hepatitis B – urticaria with jaundice (yellow hives)

DRUG REACTIONS

Hepatitis C – lichen planus, porphyria cutanea tarda, cryoglobulinemia, necrolytic acral erythema An Bras Dermatol 91:6496–51, 2016

Dapsone hypersensitivity syndrome – fulminant hepatitis Ped Transpl 18:E2402–45, 2014

Herpes simplex – HSV hepatitis; Clin Inf Dis 56:559,6136–14, 2013; infants J Pediatr 159:6086–11, 2011

DRESS syndrome – cholestasis with liver injury JAAD 72:10031– 009, 2015; morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, urticarial papular-confluent; facial edema, lymphadenopathy JAAD 82:5735–74, 2020; Ped Derm 36:3243–29, 2019; JAMADerm 152:12541–257, 2016; BJD 170:8668–73, 2014; JAAD 68:E11–4BJD 169:10711–080, 2013; BJD 168:3914–01, 2013; Am J Med 124:5885–97, 2011; Ped Derm 28:7417–43, 2011; JAAD 68:6937–05, 2013; AD 146:13731–379, 2010; NEJM 242:8978–98, 1950

Herpes zoster – VZV hepatitis Cutis 100:321,324,330, 2017; Dermatol Online J Feb 22, 2015 Infectious mononucleosis – Epstein-Barr virus; hepatitis, rarely jaundice J Emerg Med 58:e717–3, 2020

Terbinafine hepatotoxicity – fulminant hepatic necrosis

Leprosy – erythema nodosum leprosum – new painful dermal or subcutaneous nodules with fever, anorexia, malaise, arthralgias and myalgias, epididymitis, orchitis, periostitis, dactylitis, lymphadenitis, hepatosplenomegaly, glomerulonephritis, iridocyclitis, panniculitis, edema of dermis JAAD 71:7958–03, 2014; Lucio’s phenomenon – fever, anemia, hepatosplenomegaly, lymphadenopathy JAAD 83:173–0, 2020; viral co-infection with hepatitis B,C, HTLV1 PLOS Negl Trop Dis AUG 12, 2015

EXOGENOUS AGENTS

Louse-borne relapsing fever (Borrelia recurrentis) – high fever, headache, dizziness, myalgias, fatigue, hemorrhage, liver disease, renal failure; relapse ever 71–9 days JAAD 82:5515–69, 2020

Synthetic opioid MT-45 – painful intertrigo, folliculitis, dry eyes, hair depigmentation, hair loss, Mees’ lines, abnormal liver function tests BJD 176:10211–027, 2017

Measles JAMA 320:25912–592, 2018;atypical measles – exanthem, pancytopenia, abnormal liver function tests NEJM 371:3583–66, 2014

Liver Disease, Cutaneous Manifestations and Hepatic Abnormalities of Skin Disease Mediterranean spotted fever (Rickettsia conorii) – fever, flu-like symptoms, generalized eruption sparing face, involving palms and soles NEJM 371:3583–66, 2014

Stevens-Johnson syndrome Burns 42:202–7, 2016

Mycobacterium tuberculosis – abdominal pain, rash, and lymphadenopathy; papulonecrotic tuberculid NEJM 380:2752–83, 2019

METABOLIC DISORDERS

Necrotizing fasciitis – swelling, pain out of proportion to erythema, bullae, and gas in soft tissue; diabetes mellitus, liver disease; contact with marine life or ingestion of seafood Br J Surg 101:e1191–25, 2014 Parechovirus type III – young infants; high fever, poor perfusion, irritability; sepsis-like presentation; erythrodermic rash, abdominal distension, edema, hepatitis; recovery common Clin Inf Dis 60:2282–36, 2015 Parvovirus B19 – rare cause of fulminant hepatic failure Transpl Proc 51:11691–171, 2019 Q fever – granulomatous hepatitis NEJM 376:8698–74, 2017 Rat bite fever – macular and petechial rash on palms and soles; acral hemorrhagic pustules; palpable purpura; arthritis, pustules; endocarditis, pericarditis, interstitial pneumonia, hepatitis, nephritis, septic arthritis, systemic vasculitis JAMADerm 152:7237–24, 2016; J Clin Microbiol 51:19871–989, 2013; AD 148:14111–416, 2012; Clin Microbiol Rev 20:132–2, 2007; Clin Inf Dis 43:15851–586, 16161–617, 2006; JAAD 38:3303–32, 1998 Rickettsial species (R. monacensis, R massilae, R. solvaca, R helvetica, R. sibirica, R. aeschlimannii) – headache, fever, rash, tache noir, mild hepatitis (transaminitis) Eur Rev Med Pharmacol 20:26302–633, 2016 Rocky Mountain spotted fever – hepatosplenomegaly MMWR 65:14–4, May 13, 2016 Syphilis, secondary; hepatitis; high alkaline phosphatase; non-specific periportal lymphocytic infiltrate with focal necrosis; spirochetes observed with immunochemical stains Case Rep Med 2014. BD4794.doi.10.1155/2014/604794; Clin Inf Dis 62:828–3,1231–24, 2016 Viral hepatitis – morbilliform eruption; urticarial, panniculitis, scarlatiniform eruption, serum sickness like rash, cutaneous vasculitis, cryoglobulinemia, prolonged morbilliform rash G Ital DV Dec 4, 2019.doi.10.23736/SO3920–488.19.064885–

INFLAMMATORY DISORDERS Hepatocutaneous syndrome – in chronic active hepatitis; firm red papules leaving atrophic scars Br Med J i:817, 1977 Hepatic dysfunction – jaundice JAAD 57:10511–058, 2007 Hidradenitis suppurativa – non-alcoholic fatty liver J Eur Acad Dermatol 33:21312–136, 2019 Hyperbilirubinemia – jaundice JAAD 43:11–6, 2000; hyperbilirubinemia – green palms AD 146;2092–10, 2010 Hyperpigmentation – diffuse muddy gray hyperpigmentation with accentuation in perioral, periorbital, and areolar regions Inflammatory bowel disease – primary sclerosing cholangitis, small duct PSC, granulomatous hepatitis, autoimmune liver and pancreatic disease, cholestasis, gallstone formation and liver injury; aphthous stomatitis, pyostomatitis vegetans, Sweet’s syndrome, pyoderma gangrenosum, erythema nodosum Inflamm Bowel Dis 21:19821–992, 2015 Sarcoid – lupus pernio; cholestatic hepatitis, elevated alkaline phosphatase, right upper quadrant pain, jaundice, fever, hepatic granulomas, cirrhosis jaundice, bleeding tendencies Clin Liver Dis 23:3313–41, 2019; Am J Case Rep 19:12121–215, 2018; Neth J Med 70:3493–56, 2012

619

Alpha-1 antitrypsin deficiency – panniculitis Orphanet J Rare Dis June 19, 2008 Carbohydrate-deficient glycoprotein (CDG) syndrome type I – present at birth; lipodystrophic skin, sticky skin (peau d’orange), strabismus, psychomotor delay, floppy, failure to thrive, mental retardation, liver dysfunction, cerebellar ataxia, pericardial effusions Ped Derm 22:757–8, 2005 Chylous ascites – xanthomas secondary to chylous ascites JAAD 51:757–8, 2004 Cirrhosis – chronic liver disease; parotid gland enlargement; spider telangiectasias, periorbital and pedal edema, hemorrhoids, temporal wasting, caput medusa, red tongue, xerosis, trichomegaly, palmar erythema; testicular atrophy, clubbing, Terry’s nails, brittle nails, splinter hemorrhages, hypertrophic osteoarthropathy, diffuse muddy gray hyperpigmentation Cutis 89:848–8, 2012; Am J Clin Dermatol 8:3473–56, 2007 Gastroenterology 96(2 Pt 1):5105–18, 1989; splinter hemorrhages JAAD 50:2892–92, 2004; ulceration of umbilical vein; umbilical hemorrhage Postgrad Med 57:4614–62, 1981 Cryoglobulinemia, mixed; hepatitis C – retiform purpura JAAD 82:7837–96, 2020; Clin Liver Dis 21:5555–64, 2017; Am J Med 128:9509–55, 2015   Livedo reticularis   Necrolytic acral erythema   Lichen planus  Purpura  Urticaria  Vasculitis Cystinosis – white facial papules; renal failure, ocular, pancreatic, hepatic, muscular, dental, gonadal, and neurologic involvement, hypothyroidism JAMADerm 152:1081–09, 2016 Delayed puberty – biliary atresia J Pediatr Surg 25:8088–11, 1990 Fanconi’s anemia – autosomal recessive; endocrine abnormalities with hypothyroidism, decreased growth hormone, diabetes mellitus, café au lait macules, diffuse hyperpigmented macules, guttate hypopigmented macules, intertriginous hyperpigmentation, skeletal anomalies (thumb hypoplasia, absent thumbs, radii, carpal bones), oral/genital erythroplasia with development of squamous cell carcinoma, hepatic tumors, microphthalmia, ectopic or horseshoe kidney, broad nose, epicanthal folds, micrognathia, bone marrow failure, acute myelogenous leukemia, solid organ malignancies (brain tumors, Wilms’ tumor) BJD 164:2452–56, 2011; JAAD 54:10561–059, 2006 Gaucher’s disease type II – congenital ichthyosiform erythroderma, hepatosplenomegaly, progressive neurologic deterioration; deficiency of beta-glucosidase; GBA JAAD 67:13621–374, 2012 GM-1 gangliosidosis – X-linked; gingival hypertrophy, macroglossia, coarse facies, micrognathia, loose skin, inguinal hernia, delayed growth, hepatosplenomegaly, neonatal hypotonia, delayed motor development; kyphosis, cardiomyopathy, cherry red dot of retina, paddle shaped ribs JAMADerm 151:12491–250, 2015; Ped Derm 18:5345–36, 2001 Hemochromatosis – idiopathic (autosomal recessive) or secondary to chronic iron intoxication (Bantu hemochromatosis), chronic liver disease and iron overload, hepatic hemosiderosis in anemia with ineffective erythropoiesis, congenital transferrin deficiency – bluegray, bronze, gray-brown hyperpigmentation especially of face, flexures, and exposed parts JAMA 312:7437–44, 2014; J Drugs in Dermatol 9:7197–22, 2010; Clev Clin J Med 76:5996–06, 2009; AD

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113:1611–65, 1977; Medicine 34:3814–30, 1955; arthropathy JAAD 51:2052–11, 2004; Hum Molec Genet 9:23772–382, 2000; Schweiz Med Wochenschr 122:8428–49, 1992; AD 113:1611–65, 1977; Medicine 34:3814–30, 1955  Bronze or slate-gray hyperpigmentation pronounced in sunexposed skin; ichthyosiform changes Hemolytic uremic syndrome – purpura, thrombotic vasculopathy, bone pain Hypervitaminosis A – alopecia, desquamation; follicular keratoses; hepatomegaly, liver fibrosis, portal hypertension; NEJM 315:12501– 254, 1986; ichthyosiform eruption

PARANEOPLASTIC DISORDERS Carcinoid syndrome – pellagrous dermatitis (erosions from skin fragility, erythema, and hyperpigmentation over knuckles), flushing, patchy cyanosis, hyperpigmentation, telangiectasia, pellagrous dermatitis, salivation, lacrimation, abdominal cramping, wheezing, diarrhea BJD 152:717–5, 2005; AD 77:869–0, 1958 Necrobiotic xanthogranuloma with paraproteinemia – yellow-red plaques Med J Aust 200:4904–93, 2014 Pityriasis rotunda – hepatocellular carcinoma BJD 120:5455–49, 1989

Intrahepatic cholestasis of pregnancy – linear excoriations AD 143:7577–62, 2007

PRIMARY CUTANEOUS FINDINGS

Mucopolysaccharidoses – dysmorphic facies

Pruritus, generalized – hepatic disease, including intrahepatic biliary obstruction JAAD 45:8928–96, 2001; obstructive biliary disease AD 119:1831–84, 1983; primary biliary cirrhosis, cholestasis JAAD 41:4314–34, 1999; Am J Med 70:10111–016, 1981; primary ascending cholangitis; drug-induced cholestasis (chlorpromazine, birth control pills, testosterone) Semin Dermatol 14:3023–12, 1995; primary biliary cirrhosis JAAD 45:8928–96, 2001

Multiple mitochondrial respiratory chain complex deficiencies – muscle, central nervous system, cardiac, and liver involvement JAMA 312:687–7, 2014 Neutral lipid storage disease (Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma (non-bullous congenital ichthyosiform erythroderma and neutral lipid storage disease); thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles (Jordan anomaly), myopathy, fatty liver, CNS disease, deafness; lipid vacuoles in basal keratinocytes on skin biopsy Ped Derm 29:3413–44, 2012; AD 141:7988–00, 2005; Am J Dermatopathol 20:798–5, 1998; JAAD 17:8018–08, 1987; AD 121:10001–008, 1985 Niacin toxicity – flushing; acute liver failure secondary to niacin toxicity Case Rep Pediatr 2014:692530.doi.10.1155/2014/692530; diffuse microvesicular steatosis Hepatol Commun 2:12931–298, 2018 Niemann-Pick disease A,B (ASM deficiency) – hepatosplenomegaly, cherry red spot of macula of retina, interstitial lung disease Phosphoglucomutase 1 deficiency – autosomal recessive; disorder of glycosylation with impaired glycoprotein production; liver dysfunction, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, cardiac arrest NEJM 370:5335–42, 2014 Porphyria   Erythropoietic porphyria – erythema, edema, and erosions  Erythropoietic protoporphyria – retention of protoporphyrin in the liver – cholestasis, cholelithiasis, mild parenchymal liver disease, progressive hepatocellular disease; end-stage acute failure World J Gastroenterol 16:45264–531, 2010; BJD 118:1131–16, 1988  Porphyria cutanea tarda – iron overload; alcohol hepatitis C; hepatoma in long-standing PCT; fluorescent liver biopsy, skin fragility, vesicles bullae, milia, scars, hypertrichosis, sclerodermoid plaques, dystrophic calcification of the face, hands, scalp, and neck, hyperpigmentation, generalized or melisma-like J Med Case Rep 13:17, 2019  Variegate porphyria – hepatocellular carcinoma Ann Clin Bioche 52(pt 3):4074–12, 2015 Primary biliary cirrhosis – xanthelasmas and xanthomas – 10% patients J Gastrohepatol 11:10211–023, 1996

Psoriasis – metabolic syndrome, non-alcoholic fatty liver Clin Rheumatol 38:28432–850, 2019 Pustular psoriasis, generalized (von Zumbusch) – jaundice, liver abnormalities Rev Med Interne 31:e161–8, 2010 Pyostomatitis vegetans – increased alkaline phosphatase, cirrhosis, hepatitis, pericholangitis; association with ulcerative colitis and Crohn’s disease An Bras Dermatol 86:S1371–40, 2011; Med Oral Patol Oral Cir Bucal 14:E1141–17, 2009; Clin Exp Dermatol 29:17–, 2004 Vesiculopustular eruption of hepatobiliary disease Int J Derm 36:8378–44, 1997

SYNDROMES Aagenaes syndrome (hereditary cholestasis with lymphedema) – autosomal recessive; lymphedema of legs due to congenital lymphatic hypoplasia; pruritus, growth retardation; protein losing enteropathy, sclerosing cholangitis; CCBE1 mutation Scand J Clin Lab Invest 78:5665–74, 2018; Hepatology 66:2862–88, 2017 Alagille syndrome(arteriohepatic dysplasia) – paucity of interlobular hepatic ducts; autosomal dominant; pruritus and failure to thrive; dysmorphic facies, follicular hyperkeratosis, palmar linear plane xanthomas, porphyria cutanea tarda due to retained porphyrins, jaundice BJD 138:1501–54, 1998;wispy hair, triangular face, broad forehead, deep-set eyes, mild hypertelorism, straight nose, small pointed chin, ventricular hypertrophy, pulmonary artery stenosis; xanthomas; supernumerary digital flexion creases of middle phalanges; JAG1 and Notch2 mutations JAAD 58:S91–1, 2008; cutis laxa-like changes with resolution of xanthomas after liver transplantation Ped Derm 15:1992–02, 1998 Albers-Schonberg – PPK with cirrhosis Alport's syndrome – tophi

NEOPLASTIC DISEASES

Beckwith-Wiedemann syndrome (exomphalos-macroglossia-gigantism) (EMG) syndrome – autosomal dominant; zosteriform rash at birth, exomphalos, macroglossia, visceromegaly, facial salmon patch of forehead, upper eyelids, nose, and upper lip and gigantism; linear earlobe grooves, circular depressions of helices; increased risk of Wilms’ tumor, adrenal carcinoma, hepatoblastoma, and rhabdomyosarcoma JAAD 37:5235–49, 1997; Am J Dis Child 122:5155–19, 1971

Light chain deposition disease – violaceous plaque of chin; involvement of kidneys (nephropathy), liver, heart, lungs, peripheral nerves Hematol Oncol Clin NA 13:12351–248, 1999

Behcet’s disease – superficial and deep venous thrombosis, arterial aneurysms and occlusions; Budd-Chiari syndrome An Bras Dermatol 88:4484–51, 2013

Wilson’s disease – diarrhea, liver disease; azure lunulae; elastosis perforans serpiginosa; Kayser-Fleischer ring, anetoderma Clin J Gastroenterol 8:525–6, 2015; NEJM 371:12381–247, 2014

Liver Disease, Cutaneous Manifestations and Hepatic Abnormalities of Skin Disease Bifid epiglottis syndrome – accessory auricles with preauricular sinus, polycystic kidney disease with intrahepatic biliary dilatation, endocardial cushion defect, polydactyly Ped Int 52:7237–28, 2010 Bronze baby syndrome – gray-brown pigmentation after phototherapy for hyperbilirubinemia in neonates; requires liver disease; confused with central cyanosis, carbon baby syndrome, gray baby syndrome JAAD 12:3253–28, 1985; Ped Res 17:3273–30, 1983; J Pediatr 88:4614–64, 1976; JAMA 208:1703, 1969 Coffin-Siris syndrome – mutation in ARID1B; extreme obesity, macrocephaly, hepatomegaly, hyperinsulinemia, polycystic ovarian syndrome, hypertrichosis, hypoplastic or absent fifth distal phalanx or nail Eur J Hum Genet 22:13271–329, 2014 Dyskeratosis congenita(Zinsser-Cole-Engmann syndrome) (telomere syndrome) – X-linked recessive – cutaneous atrophy and pigmentation; mental retardation, short stature, deafness, conjunctivitis with obstruction of lacrimal ducts, blepharitis, palmoplantar keratoderma, palmoplantar hyperhidrosis, urethral anomalies, esophageal stenosis, choanal atresia, hepatic abnormalities including hepatomegaly, hemosiderosis, fibrosis, cirrhosis in 10% of cases; varying levels of hepatic inflammation, necrosis, nodular regenerative hyperplasia, and iron accumulation, frontal lobe atrophy, intracranial calcifications, hypogonadism, osteoporosis, avascular necrosis Indian J Anaesth 59:3123–14, 2015; Ped Derm 26:1761–79, 2009; Hum Genet 180:456–0, 2009; PLoSOne 4:e7926, 2009; J Med Genet 12:3393–54, 1975 Ehlers-Danlos syndrome type IV – spontaneous liver rupture J R Soc Med 98:3203–22, 2005; hepatic hemorrhage 34:10, 2019 H syndrome – sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, short stature, facial telangiectasia, gynecomastia, camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azoospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly JAAD 59:798–5, 2008 HELLP (hemolysis, elevated liver enzymes, low platelets) – purpura Curr Pharm Biotechnol 19:8108–26, 2018 Hemophagocytic lymphohistiocytosis syndrome – fever, pancytopenia, lymphadenopathy, hepatomegaly, splenomegaly, neurologic, joint, purpura, morbilliform eruption, kidney, and cardiac involvement, central nervous system dysfunction Eur Rev Med Pharmacol Sci, 16:14141–424, 2012; Genes Immunol 13:2892–98, 2012   Familial HLH – known genetic defects (perforin)   Immune deficiencies   Chediak-Higashi syndrome   Griscelli syndrome    X-linked lymphoproliferative syndrome  Acquired   Infections   Endogenous products   Rheumatic diseases   Neoplasms Hereditary hemorrhagic telangiectasia syndrome – recurrent and spontaneous epistaxis, multiple mucocutaneous telangiectasias; angina and heart failure due to shunting between hepatic artery and vein; portal hypertension and hepatic encephalopathy; telangiectatic hepatic fibrosis Dig Liver Dis 37:6356–45, 2005; J Belge Radiol 81:1841–85, 1998 Hunter syndrome (mucopolysaccharidosis type II) – accumulation of glycosaminoglycans; X-linked recessive; iduronate 2-sulfatase deficiency; recurrent otitis media, respiratory infections, hepatosplenomegaly, hernias, cardiomyopathy Ped Derm 33:5946–01, 2016 Hurler’s syndrome (mucopolysaccharidosis type I-H)– disorder of glycosaminoglycans accumulation; autosomal recessive; coarse

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facies, macroglossia, short stature, macrocephaly, hepatosplenomegaly, hernias, corneal clouding, vision and hearing loss; cardiac anomalies; respiratory infections; alpha-l-iduronate deficiency Ped Derm 33:5946–01, 2016 Ichthyosis-hypotrichosis-sclerosing cholangitis syndrome (neonatal ichthyosis sclerosing cholangitis syndrome) JAAD 63:6076–41, 2010; Hum Mutat 27:4084–10, 2006; Gastroenterol 127:13861–390, 2004; JID 119:707–6, 2002 IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, pemphigoid nodularis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash; thyroid dysfunction, diabetes mellitus, hepatitis, nephritis, onychodystrophy, alopecia universalis; mutations in FOXP3 (forkhead box protein 3) gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia NEJM 378:11321– 141, 2018; JAAD 73:3553–64, 2015; BJD 160:6456–51, 2009; ichthyosiform eruptions Blood 109:3833–85, 2007; BJD 152:4094– 17, 2005; NEJM 344:17581–762, 2001; alopecia areata AD 140:4664–72, 2004 Kawasaki’s disease – hepatomegaly, cholestasis Ital J Pediatr 42:27, 2016; BMC Pediatr Feb 18, 2014 Macrophage activation syndrome – morbilliform eruption and purpura; elevated liver enzymes, hepatomegaly, characteristic sudden drop in ESR due to decreased fibrinogen and liver dysfunction J Clin Gastroeneterol 45:2102–14, 2011; adult-onset Still’s disease, lupus erythematosus Necrolytic acral erythema – acral velvety hyperpigmented and hyperkeratotic plaques with rim of dusky erythema of distal dorsal feet and dorsal hands; red palms with desquamation, erythroderma with flaccid bullae, edema and desquamation of face; onychodystrophy and onychomadesis, hepatitis C Cutis 84:3013–04, 008; AD 141:858–7, 2005; AD 136:7557–57, 2000; Int J Dermatol 35;2522– 56, 1996 NOMID – (neonatal-onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – cryopyrinopathy with mutation in CIAS1(encodes cryopyrin); frontal bossing, saddle nose deformity; edematous papules and plaques, urticarial-like lesions in newborn, lesions, chronic aseptic meningitis, arthralgias of knees and ankles with disabling deforming arthropathy with epiphyseal bone formation (osseous overgrowth), deafness, hepatosplenomegaly, anterior uveitis, vitreitis, papilledema, corneal stromal keratopathy; blindness, mental retardation; high-frequency hearing loss, developmental delay; recurrent fever and rash more severe in evening; headache, macrocephaly, cerebral atrophy; mutation in NLRP3 (CIAS 1) which encodes cryopyrin Orphanet J Rare Dis 11:161–7, Dec 7, 2016; JAAD 68:8348–53, 2013; AD 144:3924–02, 2008; AD 142:15911–597, 2006; NEJM 355:5815–92, 2006; JAAD 54:3193– 21, 2006; Ped Derm 22:2222–26, 2005; AD 141:2482–63, 2005; Arthritis Rheum 52:12831–286, 2005 Omenn's syndrome – autosomal recessive; immunodeficiency; erythroderma with occasional alopecia of the scalp and eyebrows; generalized adenopathy with hepatosplenomegaly Dermatol Clin 35:111–9, 2017; Ped Derm 14:495–2, 1997; JAAD 25:4424–46, 1991 Poikiloderma with neutropenia – autosomal recessive; Navajo Indians; erythematous rash of limbs, trunk, and face beginning in infancy; evolves into poikiloderma; recurrent sinopulmonary infections; calcinosis cutis; palmoplantar keratoderma; pachyonychia of great toenails, photosensitivity; growth retardation; dental caries; atrophic scars; cryptorchidism; hepatosplenomegaly; mutation in USB1 gene; mutation in C16orf57 BJD 180:e6, 2019; BJD

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

168:6656–66, 2013; Ped Derm 29:4634–72, 2012; Eur J Med Genet 55:81–1, 2012; BJD 163:8668–69, 2010; Am J Med Genet A 146A:27622–769, 2008; Am J Hum Genet 86:727–6, 1991; Am J Hum Genet 49:A661, 1991

Hepatic hemangiomas associated with multiple cutaneous infantile hemangiomas – increased risk with greater than five cutaneous infantile hemangiomas Seminars Cut Med Surg 35:1081–16, 2016

Premature aging syndrome (Mulvihill-Smith syndrome) – premature aging and immunodeficiency; multiple congenital melanocytic nevi, freckles, blue nevi, lack of facial subcutaneous tissue, xerosis, telangiectasias, thin skin, fine silky hair, premature aging, low birth weight, short stature, bird-like facies, hypodontia, high-pitched voice, mental retardation, sensorineural hearing loss, hepatomegaly Am J Med Genet 69:566–4, 1997; J Med Genet 31:7077–11, 1994; Am J Med Genet 45:5976–00, 1993

Polyarteritis nodosa – hepatitis B in 20%; ruptured hepatic aneurysm BMJ Case Rep April 1, 2015

IgA vasculitis – retiform purpura JAAD 82:7837–96, 2020

Takayasu’s arteritis – peliosis hepatis (hepatic sinusoidal dilatation) Ann Hepatol 10:5595–61, 2011 Thrombotic thrombocytopenic purpura Hematol Oncol Clin NA 31:10811–103, 2017

Pseudoglucagonoma syndrome with alcoholic liver disease AD 138:4054–10, 2002; pseudoglucagonoma syndrome due to malnutrition AD 141:9149–16, 2005; with chronic liver disease, chronic pancreatitis, traumatic necrotizing pancreatitis, celiac disease, jejunal adenocarcinoma AD 115:14291–432, 1979

LYMPHADENOPATHY FOR THE  DERMATOLOGIST

Schnitzler's syndrome – chronic urticaria, intermittent fever, and IgM monoclonal gammopathy (macroglobulinemia), high ESR, leukocytosis, arthralgia, arthritis, with disabling bone pain (osteosclerotic) of distal femur and proximal tibia, palpable lymphadenopathy, hepatosplenomegaly JAAD 68:8348–53, 2013; AD 143:10461–050, 2007; JAAD 56:S1201–22, 2007; J Eur Acad Dermatol Venereol 16:2672–70, 2007; BJD 142:9549–59, 2000; JAAD 30:3163–18, 1994; AD 130:11931–198, 1994; JAAD 20:8558–57, 1989; JAAD 20:2062–11, 1989

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSFUNCTION

Shwachman-Diamond syndrome – periodontal disease and caries; abscesses, short stature, delayed puberty, skeletal changes, pancreatic exocrine deficiency, pancytopenias, failure to thrive, hepatomegaly, pneumonia, otitis media, osteomyelitis Ped Derm 28:5685–69, 2011 Sly syndrome (mucopolysaccharidosis type VII) – autosomal recessive; beta-glucuronidase deficiency; coarse facial features, corneal clouding, short stature, cardiac disease, macroglossia, hepatosplenomegaly, skeletal abnormalities Intractable Rare Dis Res 9:19–, 2020; Ped Derm 33:5946–01, 2016 Zimmermann-Laband syndrome – autosomal dominant; dysplastic/ absent nails, large ears and nose, hepatosplenomegaly, short terminal phalanges, hyperextensible metacarpophalangeal joints Ped Derm 18:5345–36, 2001

TOXINS Alcoholic pancreatitis and cirrhosis – zinc deficiency Int J Dermatol 34:6516–52, 1995; AD 114:9379–39, 1978; Arsenic toxicity – acral keratoses; hepatosplenomegaly; portal hypertension, fibrosis, chronic lung disease; peripheral neuropathy, hyperpigmentation Kaohsiung J Med Sci 27:3603–70, 2011 Lead poisoning NEJM 370:15421–550, 2016; Scott Med J 24:3183–21, 1979

TRAUMA Retroperitoneal bile leakage – after cholecystectomy; well demarcated jaundice of hips, extending to 3 cm below the clavicles (to the fascia of Scarpa) Ann Int Med 142:3893–90, 2005

VASCULAR DISORDERS Giant cell arteritis (granulomatous vasculitis) – abnormal liver function tests, abdominal pain and liver biopsy with non-caseating epithelioid cell granulomatous inflammation of medium-sized arterioles in portal tracts Rheumatology (Oxford)50:23162–317, 2011

Med Oncol 19:1771–79, 2002; Semin Oncol 20:5705–82, 1993; J Gen Int Med 2:495–8, 1987

Severe atopic dermatitis, elevated IgE levels, and recurrent infections Dermatol Clin 35:111–9, 2017   DOCK8 syndrome   Hyper IgE syndrome (Job’s syndrome)  Omenn’s syndrome – severe combined immunodeficiency; severe erythroderma, infections, lymphadenopathy, hepatosplenomegaly  Phosphoglucomutase 3(PGM3) deficiency – atopy and hypergammaglobulinemia, developmental delay  STK4 or Macrophage-Stimulating 1(MST1) deficiency – cutaneous viral, bacterial, fungal infections; respiratory infections, cardiac anomalies   Tyk2 deficiency  Wiskott-Aldrich syndrome – X-linked recessive; T-cell lymphopenia, autoimmunity, malignancy recurrent bacterial and viral infections, vascular abnormalities, microthrombocytopenia CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – recurrent annular red or violaceous plaques of the face (periorbital erythema) and trunk which become purpuric and result in residual annular hyperpigmentation; purple swollen eyelids and lips (thick lips), urticarial papules; oral ulcers; lipoatrophy of cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of lateral forehead, gynecomastia, wide spaced nipples, nodular episcleritis and limitation of range of motion with plaques over interphalangeal joints; periorbital edema with arthralgia without arthritis, panniculitis, lipoatrophy, aseptic meningitis, nodular conjunctivitis, episcleritis, lymphadenopathy, ear and nose chondritis, epididymitis, cold-induced pernio-like lesions of hands and feet, delayed physical development, splenomegaly, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, splenomegaly, protuberant abdomen; pleuritic chest pain Ped Derm 33:6026–14, 2016; BJD 170:2152–17, 2014; JAAD 68:8348–53, 2013; Ped Derm 28:5385–41, 2011; JAAD 62:4874–95, 2010 Chronic granulomatous disease – massive lymphadenopathy NEJM 367:753, 2012 Dermatomyositis Hyper IgD syndrome – periodic fever, red macules, urticaria, annular erythema, nodules, arthralgias, abdominal pain, lymphadenopathy Ped Derm 35:4824–85, 2018; AD 130:596–5, 1994 IgG4-related disease – indurated nodules of the neck, cheek, temporal region, periauricular; lymphadenopathy NEJM 376:7757–

Lymphadenopathy for the Dermatologist 623 86, 2017; JAMADerm 152:5695–70, 2016; Adv Anat Pathol 20:101–6, 2013; Eur J Dermatol 23:2412–45, 2013; JAMADerm 149:7427–47, 2013; sclerosing mesenteritis (retractile mesenteritis) – sclerodermoid changes with subcutaneous nodules AD 146:10091–013, 2010

Diphtheria – bull neck due to lymphadenopathy, myocarditis, peripheral neuropathy, pharyngitis with membranes Netter’s Infectious Diseases pp.51–0, 2012

Lupus erythematosus, systemic – 50% patients develop nontender, soft, discrete 0.52–cm cervical, axillary, and inguinal adenopathy

Filariasis – lymph node of groin with scrotal, vulvar, leg edema, breast edema JAAD 73:9299–44, 2015

Rheumatoid arthritis

Folliculitis decalvans NEJM 369:23332–343, 2013

Serum sickness

Gianotti-Crosti syndrome (Epstein-Barr virus) – papular facial and extensor extremity dermatitis with lymphadenopathy JAAD 72:11–9, 2015

Still’s disease

DRUG REACTIONS

Epstein-Barr virus infection, including infectious mononucleosis NEJM 369:23332–343, 2013

Glanders Granuloma inguinale Dermatol Clin 33:5956–07, 2015

DRESS syndrome Ped Derm 36:3243–29, 2019

Hepatitis B, acute

Drugs  Allopurinol  Atenolol  Captopril  Carbamazepine  Cephalosporins  Gold  Hydralazine  Penicillin  Phenytoin  Primidone  Pyrimethamine  Quinidine  Sulfonamides  Sulindac

Acute HIV disease – diffuse lymphadenopathy; lymph nodes decrease in size after the acute stage; pharyngitis, fever, generalized exanthem sparing face, elevated liver functions

INFECTIONS AND INFESTATIONS Adenovirus infection – pharyngoconjunctival fever NEJM 369:23332–343, 2013 African tick bite fever (Rickettsia africae) – hemorrhagic pustule, purpuric papules; transmitted by Amblyomma hebraeum, A. variegatum (Bont ticks) – high fever, headache, arthralgia, myalgia, malaise, fatigue, rash in 23– days, with eschar, widespread exanthem with maculopapules, vesicles, and pustules JAAD 70:9599–61, 2014; AD 146:6416–48, 2010; JAAD 48:S181–9, 2003 Anthrax NEJM 374:5735–81, 2016 Bartonellosis NEJM 369:23332–343, 2013 Brucellosis Bubonic plague – Yersinia pestis; Xenopsylla cheopis (Oriental rat flea); 26– day incubation period; fever, painful lymphadenitis, buboes; septicemia with disseminated intravascular coagulation NEJM 372:9549–62, 2015; Cutis 86:2822–84, 2010 Cat scratch disease – unilateral conjunctivitis with lymphadenopathy (Parinaud’s oculoglandular syndrome); optic nerve swelling, neuroretinitis with blindness NEJM 374:5735–81, 2016; JAAD 70:7958–19, 2014; inguinal adenopathy – inguinal pain and swelling; loss of consciousness, seizures NEJM 372:20502–058, 2015 Chagas’ disease Cowpox – human cowpox with fingertip necrosis and arm abscess, lymphangitis, lymphadenopathy Clin Inf Dis 69:1791–81, 2019 Cryptococcosis J Cytol 29:2002–02, 2012 Cytomegalovirus infection NEJM 369:23332–343, 2013 Dengue fever Dental sinus and dental abscess NEJM 369:23332–343, 2013

NEJM 371:3583–66, 2014 Histoplasmosis Clin Inf Dis 70:10031–010, 2020 HTLV 1 and 2 Human T-lymphotropic virus type I-associated infective dermatitis – chronic relapsing dermatitis; severe red and exudative dermatitis with scaling and crusting of scalp, forehead, eyelids, paranasal area, neck, retroauricular, external ear, axillae, groin; chronic watery nasal discharge, crusting of anterior nares, blepharoconjunctivitis; generalized fine papular rash with lymph nodes; onset of rash at age 2 years; most common form of transmission is breast feeding; harbinger of development of adult T-cell lymphotropic leukemia and HTLV-1-associated myelopathy (HAM)/tropical spastic paralysis (TSP); Jamaica, Senegal, Brazil (endemic areas) JAAD 64:1521– 60, 2011; Proc Natl Acad Sci USA 77:74157–419, 1980; BJD 79:2292–36, 1967; BJD 78:931–00, 1966 Infectious mononucleosis (Epstein-Barr virus) – symmetric lymphadenopathy with posterior cervical nodes larger than anterior; kidney-­shaped lymph nodes; axillary and inguinal lymphadenopathy helps to distinguish mono from other causes of pharyngitis JAAD 72:11–9, 2015; Clin Inf Dis 59:95,1361–37, 2014 Insect bite reactions – giant bullae due to hypersensitivity to mosquito bites in patients with Epstein-Barr virus infection JAAD 72:11–9, 2015 Kala-azar (visceral leishmaniasis) Kerion NEJM 369:23332–343, 2013 Leishmaniasis Clin Dermatol 38:1521–59, 2020; L. braziliensis – pian bois JAAD 73:8979–08, 2015 Leprosy – erythema nodosum leprosum – new painful dermal or subcutaneous nodules with fever, anorexia, malaise, arthralgias and myalgias, epididymitis, orchitis, periostitis, dactylitis, lymphadenitis, hepatosplenomegaly, glomerulonephritis, iridocyclitis, panniculitis, edema of dermis JAAD 83:173–0, 2020; JAAD 71:7958–03, 2014; Lucio’s phenomenon – fever, anemia, hepatosplenomegaly, lymphadenopathy JAAD 83:173–0, 2020; Leptospirosis Lipschutz ulcer (ulcus vulvae acutum) (genital ulcers in teenagers) – acute genital (vulvar) ulcer accompanying tonsillitis and fever with flu-like symptoms; Epstein-Barr virus in 1/3 of patients; inguinal adenopathy JAAD 72:11–9, 2015; Cutis 91:2732–76, 2013; JAAD 63:445–1, 2010; AD 145:384–5, 2009; Ped Derm 25:1131–15, 2008; Eur J Dermatol 13:2972–98, 2003; J Pediatr 11:185, 1998; Obstet Gynecol 92:642, 1998; Sex Transm Infec 74:2962–97, 1998; BJD 135:6636–65, 1996; Genitourin Med 70:356, 1994; Acta DV 45:2212–22, 1965; Archives of Dermatology Syphilol 20:3633–96, 1912; associated with upper respiratory infections, viral gastroen-

624 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 teritis, Epstein-Barr virus, cytomegalovirus, Mycoplasma, influenza A, streptococcal pharyngitis, mumps JAAD 68:8858–96, 2013 Lyme disease

Tick-borne lymphadenopathy (Rickettsia slovaca, R. rioja, R. raoultii); Dermacentor marginatus – scalp eschar with facial edema; residual alopecia JAAD 75:11–6, 2016

Lymphogranuloma venereum Dermatol Clin 33:5956–07, 2015;

Tinea capitis – personal observation

Measles

Toxoplasmosis (Toxoplasma gondii) – nontender adenopathy NEJM 369:23332–343, 2013; small nontender lymphadenopathy

Monkeypox – cervical, maxillary, and inguinal adenopathy; headache, fatigue; rash begins on the face and moves downward; begins as macular eruption then popular, vesicular, pustular Clin Inf Dis 58:2602–67, 2014 Mycobacterium avium complex – children Mycobacterium marinum Clin Inf Dis 37:3903–97, 2003; NEJM 374:5735–81, 2016 Mycobacterium scrofulaceum – children Mycobacterium tuberculosis – in adults Myiasis – Hypoderma tarandi (bumblebee-like fly) attaches eggs on hair of reindeer (caribou) (Rangifer tarandus) in Norway and Sweden; facial skin colored nodules; red papule of eyelid with edema of eyelid NEJM 367:24562–457, 2012 Onchocerciasis (Onchocerca volvulus) – painless lymphadenopathy with hanging groin JAAD 80:12151–231, 2019; JAAD 73:9299–44, 2015 Parinaud's oculoglandular fever – leptospirosis, cat scratch disease, tuberculosis Pharyngitis NEJM 369:23332–343, 2013 Zoonotic orthopoxvirus – teats of cows as source; targetoid bullae of hands and fingers healing with eschars; edema of hands; fever; axillary lymphadenopathy NEJM 372:2232–30, 2015 Otitis externa NEJM 369:23332–343, 2013 Rickettsia parkeri rickettsiosis – regional lymphadenopathy with eschar MMWR 65:14–4, May 13, 2016 Rickettsia slovaca (Hungary) – Dermacentor marginatus or D. reticulatus tick bite; erythema marginatum-like lesions; scalp papules, crusted scalp papules and subsequent alopecia; tick-borne lymphadenopathy Clin Inf Dis 34:13311–336, 2002 Rickettsia species 364D – eschar and regional lymphadenopathy; no rash MMWR 65:14–4, May 13, 2016 Rickettsial pox (Rickettsia akari) NEJM 374:5735–81, 2016; JAAD 51:S1371–42, 2004 Rubella – posterior cervical adenopathy NEJM 369:23332–343, 2013 Scalp infection NEJM 369:23332–343, 2013 Scarlet fever – personal observation Scrub typhus (Orientia tsutsugamushi) (trombiculid mite (leptotrombidium)) – eschar and lymphadenopathy; fever, headache, morbilliform eruption, anorexia Ped Derm 34:142–7, 2017 Severe fever with thrombocytopenia (STS bunyavirus) – fever, nausea and vomiting, abdominal pain, myalgia, lymphadenopathy, confusion, headache, conjunctival congestion, and cough NEJM 364:15231–532, 2011 Sporotrichosis NEJM 374:5735–81, 2016 Streptocerciasis – Mansonella streptocerca – similar rash to onchocerciasis; acute or lichenified papules with widespread lichenification and hypopigmented macules; pruritus, lymphadenopathy JAAD 73:9299–44 2015 Syphilis, secondary – syphilitic necrotizing lymphadenitis NEJM 371:25112–520, 2014; painful shallow ulcers; may be serpiginous or snail track ulcers NEJM 371:3583–66, 2014; NEJM 362:7407–48, 2010

NEJM 362:19932–000, 2010 Trench fever(Bartonella Quintana) – red macules, 1cm or less; headache, dizziness, fever lasting 48– days, malaise, chills, conjunctivitis, myalgias, arthralgias, severe shin pain, lymphadenopathy, evanescent rash; “culture negative endocarditis” JAAD 82:5515–69, 2020; Clinics in Dermatol 28:4834–88, 2010 Trichosporon asahii – in Job’s syndrome Med Mycol 40:838–6, 2002 Tularemia(Francisella tularensis) – glandular tularemia; regional lymphadenopathy without ulcer; ulceroglandular – percutaneous inoculation with ulcer and tender regional adenopathy; inhalational tularemia with pneumonia, tonsillitis, pharyngitis with cervical lymphadenopathy NEJM 374:5735–81, 2016; MMWR 62:9639–66, 2013; ingesting raw grapes; diarrhea cervical adenopathy, fever, difficulty swallowing NEJM 379:1971–98, 2018 Tuberculosis NEJM 369:23332–343, 2013 Typhoid fever Ulcers with regional adenopathy – anthrax, ecthyma, Pasteurella multocida infection, sporotrichosis, cat scratch disease, plague, glanders, lymphogranuloma venereum, tularemia JAAD 49:3633– 92, 2003 Viral exanthema West Nile fever Winterbottom’s sign – posterior cervical chain adenopathy in trypanosomiasis

INFILTRATIVE DISORDERS Amyloidosis Diffuse infiltrative lymphocytosis syndrome (DILS) – personal observation Langerhans cell histiocytosis JAAD 78:10471–056, 2018 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – painless cervical lymphadenopathy Semin Diagn Pathol 7:197–3, 1990; Arch Pathol 87:637–0, 1969; acneiform lesions, conglobate acneiform, or red plaques with pustules JAAD 50:1591– 61, 2004; JAAD 41:3353–37, 1999; J Cutan Pathol 20:3683–74, 1993; violaceous, red papules and nodules; cervical lymphadenopathy; also axillary, inguinal, and mediastinal adenopathy Am J Dermatopathol 17:3843–88, 1995; Cancer 30:11741–188, 1972

INFLAMMATORY DISORDERS Cloquet’s node – first lymph node underneath the inguinal ligament; can be mistaken for femoral hernia when enlarged Dissecting cellulitis – cervical adenopathy JAAD 75:11011–117, 2016 Giant lymph node hyperplasia (Castleman's syndrome)- papular eruption JAAD 26:1051–09, 1992 Inflammatory pseudotumor – lymph nodes demonstrate fibrosis and inflammation Kikuchi-Fujimoto disease – young Asians; fever, often painful lymphadenopathy, respiratory symptoms, arthralgias and myalgias; macules, patches, ulcers, red plaques, and papules, facial ery-

Lymphadenopathy for the Dermatologist 625 thema, red macules and patches; scattered indurated nodules, photoeruptions; leukocytoclastic vasculitis; pruritus, conjunctival injection, pharyngitis with oral ulcers JAAD 72:11–9, 2015; NEJM 369:23332–343, 2013; Int J Dermatol 51:5645–67, 2012; Indian J Otolaryngol Head Neck Surg 63:Suppl 1:1101–12, 2011; Arch Pathol Lab Med 134:2892–93, 2010; JAAD 59:1301–36, 2008; Clin Rheumatol 26:505–4, 2007; BJD 144:8858–89, 2001; JAAD 36:3423–46, 1997 Kimura’s disease – inflammatory condition of the subcutaneous tissue and lymph nodes usually of head and neck with elevated IgE and eosinophilia NEJM 369:23332–343, 2013 Lund’s nodes – lymph node found in Calot’s triangle (triangle bounded by the cystic artery, cystic duct, and the hepatic duct); sentinel node of the gall bladder Neutrophilic sebaceous adenitis – annular expanding red plaques of face and back with fever, lymphadenopathy JAMADerm 150:12251– 226, AD 129:9109–11, 1993

thy JAAD 56:S384–0, 2007; Dermatol 189:251, 1994; JAAD 31:8979–00, 1994; AD 122:1314, 1986 Post-transplant Epstein-Barr virus-associated lymphoproliferative disorder – ulcerated plaques JAAD 51:7787–80, 2004; AD 140:11401–164, 2004 Rhabdomyomatous mesenchymal hamartoma – tonsillar hypertrophy Ped Derm 32:2562–62, 2015 Rotter’s lymph node – lymph nodes between the pectoralis minor and pectoralis major; can be site of involvement of breast cancer Squamous cell carcinoma – HPV-associated oropharyngeal squamous cell carcinoma NEJM 375:2016 Virchow’s node (Troisier’s node) – left supraclavicular adenopathy associated with gastrointestinal and pelvic malignancies; abdominal and pelvic tumors uniformly metastasized to left supraclavicular lymph node; malignancies of the head and neck, thorax, breast, skin, and lymphoma show no significant difference in laterality

Pseudolymphoma Sarcoidosis NEJM 369:23332–343, 2013

PRIMARY CUTANEOUS DISEASE Epidermolysis bullosa

METABOLIC DISORDERS

Exfoliative erythroderma – multiple causes AD 108:7887–97, 1973

Hyperthyroidism Lipid storage diseases

NEOPLASTIC DISEASES Angioimmunoblastic T-cell lymphoma – fever, lymphadenopathy, hepatosplenomegaly, hemolytic anemia, polyclonal hypergammaglobulinemia (formerly angioimmunoblastic lymphadenopathy – polyarthritis, rash, and lymphadenopathy Clin Rheumatol 17:1481–51, 1998 Castleman’s disease – angiofollicular lymph node hyperplasia causing massive lymphadenopathy Delphian nodes – lymph nodes in midline of the thyrohyoid membrane; can be involved in thyroid cancer or subacute thyroiditis Extramammary Paget’s disease BJD 164:2002–03, 2011 Irish’s node – left axillary adenopathy associated with metastatic disease (e.g., gastric cancer) Lymphoma/leukemia – Richter transformation – transformation of chronic lymphocytic leukemia to high-grade lymphoma – red nodules and plaques of arm with generalized lymphadenopathy BJD 172:5135–21, 2015; B-cell lymphoma – groove sign – personal observation; chronic lymphocytic leukemia; Sezary syndrome, cutaneous T-cell lymphoma – personal observation; human T-lymphotrophic virus type I-associated infective dermatitis – chronic relapsing dermatitis; severe red and exudative dermatitis with scaling and crusting of the scalp, forehead, eyelids, paranasal area, neck, retroauricular, external ear, axillae, groin; chronic watery nasal discharge, crusting of anterior nares, blepharoconjunctivitis; generalized fine popular rash with lymph nodes; onset of rash at age 2 years; most common form of transmission is breast feeding; harbinger of development of adult T-cell lymphotropic leukemia and HTLV-1 associated myelopathy (HAM)/tropical spastic paralysis (TSP); Jamaica, Senegal, Brazil (endemic areas) JAAD 64:1521– 60, 2011; Proc Natl Acad Sci USA 77:74157–419, 1980; BJD 79:2292–36, 1967; BJD 78:931–00, 1966 Metastases, prostate cancer; melanoma NEJM 366:1526, 2012 Plasmacytomas – primary cutaneous plasmacytosis – brown-red macules; polyclonal hypergammaglobulinemia and lymphadenopa-

SYNDROMES Blau or Jabs syndrome(familial juvenile systemic granulomatosis) – autosomal dominant; onset under 4 years of age; generalized micropapular rash of trunk and extremities infancy (ichthyosiform); translucent skin-colored papules (non-caseating granulomas) of trunk and extremities or dense lichenoid yellow to red-brown papules with grainy surface with anterior or panuveitis, synovitis, symmetric granulomatous polyarthritis; polyarteritis, multiple synovial cysts; red papular rash in early childhood; exanthema resolves with pitted scars; camptodactyly (flexion contractures of PIP joints); no involvement of lung or hilar nodes; sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathies, interstitial lung disease, nephritis, arterial hypertension, pericarditis, pulmonary embolism, hepatic granulomas, chronic renal failure; activating mutations in NOD2(nucleotide-binding oligomerization domain 2) (caspase recruitment domain family, member 15; CARD 15) Ped Derm 34:2162–18, 2017; Ped Derm 27:697–3, 2010; AD 143:3863–91, 2007; Clin Exp Dermatol 21:4454–48, 1996; J Pediatr 107:6896–93, 1985 H syndrome – autosomal recessive; facial telangiectasias; sclerodermoid changes of middle and lower body with overlying hyperpigmentation sparing the knees and buttocks; hypertrichosis, short stature, facial telangiectasia, gynecomastia, camptodactyly of 5th fingers, scrotal masses with massively edematous scrotum obscuring the penis, hypogonadism, azoospermia, sensorineural hearing loss, cardiac anomalies, hepatosplenomegaly; Arabic Palestinian population; gluteal lipoatrophy; hyperpigmentation, hearing loss, diabetes mellitus, lymphadenopathy, hypertrichosis, heart anomalies, micropenis, hallux valgus, hyperpigmentation induration and hypertrichosis of inner thighs and shins (sclerodermoid), chronic diarrhea, anemia, dilated lateral scleral vessels, episcleritis, exophthalmos, eyelid swelling, varicose veins, chronic rhinitis, renal abnormalities, bone lesions, arthritis, arthralgia; mutation in SLC29A3 JAAD 70;808–8, 2014; BJD 162:11321–134, 2010; Ped Derm 27:656–8, 2010; JAAD 59:798–5, 2008 Hemophagocytic lymphohistiocytosis syndrome – fever, pancytopenia, lymphadenopathy, hepatomegaly, splenomegaly, neurologic, joint, purpura, morbilliform eruption, kidney, and cardiac involve-

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ment, central nervous system dysfunction Eur Rev Med Pharmacol Sci, 16:14141–424, 2012; Genes Immunol 13:2892–98, 2012   Familial HLH – known genetic defects (perforin)   Immune deficiencies   Chediak-Higashi syndrome   Griscelli syndrome    X-linked lymphoproliferative syndrome  Acquired   Infections   Endogenous products   Rheumatic diseases   Neoplasms Kawasaki’s disease – cheilitis, meningitis, and unilateral cervical adenopathy in children JAAD 69:5015–10, 2013; adults JAAD 69:5015–10, 2013 Omenn's syndrome – autosomal recessive; immunodeficiency; erythroderma with occasional alopecia of scalp and eyebrows; generalized adenopathy with hepatosplenomegaly Ped Derm 14:495–2, 1997; JAAD 25:4424–46, 1991 Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) Ped Derm 33:6026–14, 2016 Schnitzler's syndrome – chronic urticaria, intermittent fever, and IgM monoclonal gammopathy (macroglobulinemia), high ESR, leukocytosis, arthralgia, arthritis, with disabling bone pain (osteosclerotic) of distal femur and proximal tibia, palpable lymphadenopathy, hepatosplenomegaly AD 143:10461–050, 2007; JAAD 56:S1201– 22, 2007; J Eur Acad DV 16:2672–70, 2007; BJD 142:9549–59, 2000; JAAD 30:3163–18, 1994; AD 130:11931–198, 1994; JAAD 20:8558–57, 1989; JAAD 20:2062–11, 1989 STING-associated vasculopathy with onset in infancy – red facial plaques, acral violaceous plaques and acral cyanosis, distal ulcerative lesions with infarcts, gangrene of fingers or toes, nasal septal perforation, nail dystrophy; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis; gain of function mutation in TMEM173(stimulator of interferon genes) NEJM 371:5075–18, 2014

CHRONIC LYMPHADENOPATHY Cutis 85:374–2, 2010 AIDS Bartonellosis Castleman’s disease NEJM 369:23332–343, 2013 Chronic pseudolymphomatous lymphadenopathy Coccidioidomycosis Connective tissue disease Cryptococcosis Cytomegalovirus infection Epstein-Barr virus infection Head and neck cancer NEJM 369:23332–343, 2013 Hematopoietic disease Kikuchi’s disease Leukemia Systemic lupus erythematosus NEJM 369:23332–343, 2013 Lymphogranuloma venereum

Lymphoma – non-Hodgkin’s lymphoma, Hodgkin’s disease Metastatic disease Non-tuberculous acid-fast bacteria Sarcoid Sinus histiocytosis Sporotrichosis Tuberculosis Tularemia

LYMPHEDEMA, PRIMARY JAAD 77:10121–013, 2017 Capillary malformation-AVM syndrome including Parkes Weber; RASA1 Choanal atresia, lymphedema syndrome PTPN14 Cholestasis lymphedema syndrome (Aagenaes syndrome) – (LCS1) Congenital lymphedema Ectodermal dysplasia, anhidrotic with immunodeficiency, osteopetrosis, and lymphedema; IKBKG Fetal chylothorax – ITGA9; hydrops fetalis Hennekam lymphangiectasia-lymphedema syndrome – (CCBE1); lymphedema of the face and legs, intestinal lymphangiectasia, intellectual defect, facial dysmorphism Hennekam lymphangiectasia-lymphedema syndrome 2 – (FAT4) Hereditary lymphedema type IA (primary congenital, Milroy’s disease); mutation in FLT4(VEGFR3) Hereditary lymphedema type IB; LYMPH1B Hereditary lymphedema type IC – (GJC2) (CX47); 4-limb late-onset lymphedema Hereditary lymphedema type ID (Milroy-like); VEGFC Hereditary lymphedema type II (Meige’s syndrome – LMPH2 Klippel-Trenaunay-Weber syndrome (KTWS) – limb overgrowth, cutaneous angiomas, venous disease, lymphedema Lymphedema-distichiasis syndrome (FOXC2) – late-onset lymphedema, secondary set of aberrant eyelashes arising from Meibomian glands, ptosis, venous reflux Lymphedema praecox Microcephaly, chorioretinopathy, lymphedema, mental retardation syndrome; KF11(EG5) Noonan’s syndrome – 1(PTPN11), 2(SOS1), 3(KRAS) – short stature, hypertelorism, nuchal edema, pigmented nevi, café au lait macules, keratosis pilaris atrophicans, keloids, coarse light colored curly hair, hypogonadism, pulmonic stenosis Oculodental dysplasia/lymphedema syndrome; GJA1(CX43) Tuberous sclerosis 1(TSC1), 2(TSC2) – facial angiofibromas, gingival fibromas, ash-leaf macules, dental enamel pits, neuropsychiatric defects, lymphedema Turner’s syndrome – 45XO, SHOX; webbed neck, low posterior hairline, lymphedema, primary amenorrhea, aortic coarctation Yellow nail syndrome – yellow nails, late-onset lymphedema, respiratory tract involvement

MACROCEPHALY

Fragile X syndrome – long narrow face, large ears, flexible fingers, large testicles, soft skin, hypotonia

Increase in occipitofrontal circumference at least two standard deviations caused by structural abnormalities of the cranium, brain, CSF, and related structures

Fucosidosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 128–129 Geroderma osteodysplastica (Bamatter syndrome) (osteodysplastic geroderma) – autosomal recessive; short stature, cutis laxa-like changes with drooping eyelids and jowls (characteristic facies with hypoplastic midface), alopecia, bone fragility with osteoporosis and skeletal abnormalities, scoliosis; lax wrinkled, atrophic skin, joint hyperextensibility, growth retardation; macrocephaly Ped Derm 23:467–472, 2006; Ped Derm 16:113–117, 1999; Am J Med Genet 3:389–395, 1979; Hum Genet 40:311–324, 1978; Ann Paediatr 174:126–127, 1950

Achondrogenesis – macrocephaly, micromelia, hydrops Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp. 212–213 Acromegaly Pituitary 19:560–564, 2016 Adams-Oliver syndrome AKT serine/threonine kinase – megalencephaly-capillary malformation syndrome/megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome – AKT3, PIK3R2, PIK3CA JAAD 68:885–896, 2013

Glutaric aciduria type 1 – autosomal recessive; Amish

Albright’s hereditary osteodystrophy – pseudohypoparathyroidism, round face, short neck, osteomas of the skin with overlying hyperpigmentation, short stature, hypogonadism, macrocephaly, psychomotor retardation, endocrinologic abnormalities; mutation in GNAS1 Ped Derm 28:135–137, 2011; Endocrinology 30:922–932, 1942 Alexander disease – autosomal dominant leukodystrophy Bannayan-Riley-Ruvalcaba syndrome – autosomal dominant, macrocephaly, developmental delay, pseudopapilledema, pigmented macules of the glans penis, hamartomatous growths including subcutaneous and visceral lipomas, gastrointestinal polyposis, capillary and combined malformations, café au lait macules, testicular enlargement, thyroiditis, hyperextensible joints, pectus excavatum, scoliosis; PTEN mutation JAAD 68:189–209, 2013; JAAD 56:541–564, 2007 Canavan disease – autosomal recessive; degenerative disease Coffin-Siris syndrome – mutation in ARID1B; extreme obesity, macrocephaly, hepatomegaly, hyperinsulinemia, polycystic ovarian syndrome, hypertrichosis, hypoplastic or absent fifth distal phalanx or nail Eur J Hum Genet 22:1327–1329, 2014 Cornelia de Lange syndrome Costello syndrome – autosomal dominant; RASopathy; loose folds with extra skin of the hands and feet; flexible joints, short stature, hypertrophic cardiomyopathy, distinctive facial features

Happle-Tinschert syndrome – segmental basaloid follicular hamartomas, basal cell carcinomas, linear hypo- or hyperpigmented lesions, linear atrophoderma, palmoplantar pitting, atrophoderma, ipsilateral hypertrichosis, hypotrichosis; polydactyly, syndactyly, rudimentary ribs, limb-length disparities, dysmorphic facies, macrocephaly, jaw ameloblastomas, dental anomalies, imperforate anus, colon adenocarcinoma; medulloblastoma cerebral manifestation, developmental delay, optic glioma or meningioma, cataracts, microphthalmia , coloboma; mutation in SMOc.1234>T BJD 182:212–217, 2020; BJD 169:1342–1345, 2013; Ped Derm 28:555–560, 2011; JAAD 65:e17–19, 2011; Dermatology 218:221– 225, 2009; Acta DV 88:382–387, 2008 Hurler’s syndrome – disorder of glycosaminoglycan accumulation; autosomal recessive; coarse facies, macroglossia, short stature, macrocephaly, hepatosplenomegaly, hernias, corneal clouding, vision and hearing loss; cardiac anomalies; respiratory infections; alpha-l-­iduronate deficiency Ped Derm 33:594–601, 2016 Klippel-Trenaunay syndrome Curr Opin Pediatr 29:448–454, 2017 Lenz-Majewski syndrome Am J Med Genet A 179:2039–2042, 2019 Macrocephaly-alopecia-cutis laxa-scoliosis syndrome (MACS) (RIN2 syndrome) – droopy eyelids, everted lips, gingival hypertrophy, dental anomalies, alopecia, high-pitched voice; mutation in RIN2 Am J Med Genet A 170:2408–2415, 2016; JAAD 66:842–851, 2012

Curry-Jones syndrome – linear hypo- or hyperpigmented lesions, palmoplantar pitting, streaks of atrophy, hypertrichosis, trichoblastomas and nevus sebaceous, polydactyly or preaxial polysyndactyly, dysmorphic facies, macrocephaly, microcephaly, dental anomalies, craniosynostosis, anal stenosis, myofibromas and smooth muscle hamartomas, medulloblastomas, cerebral malformations (agenesis of the corpus callosum), developmental delay, cataracts, microphthalmia, coloboma, glaucoma, cryptorchidism; mutation in SMOc.1234C>T BJD 182:212–217, 2020; Clin Dysmorphol 4:116–129, 1995

Macrocephaly-capillary malformation syndrome – formerly macrocephaly-­CMTC (cutis marmorata telangiectatica congenita syndrome) – macrocephalic neonatal hypotonia and developmental delay; frontal bossing, segmental overgrowth, syndactyly, asymmetry, distended linear and serpiginous abdominal wall veins, patchy reticulated vascular stain without atrophy; telangiectasias of the face and ears; midline reticulated facial nevus flammeus (capillary malformation) (vascular stains) involving the philtrum and upper lip, hydrocephalus, skin and joint hypermobility, hyperelastic skin, thickened subcutaneous tissue, polydactyly, 2–3 toe syndactyly, post-axial polydactyly, hydrocephalus, frontal bossing, hemihypertrophy with segmental overgrowth; neonatal hypotonia, developmental delay; gain-of-function mutation in phosphoinositide-3-kinase pathway (PIK3CA, AKT3, PIK3R2) JAAD 77:874–878, 2017; BJD 175:810–814, 2016; Ped Derm 29:384–386, 2012; Ped Derm 26:342–346, 2009; AD 145:287–293, 2009; JAAD 58:697–702, 2008; Ped Derm 24:555–556, 2007; JAAD 56:541–564, 2007; Ped Derm 16:235–237, 1999; Genet Couns 9:245–253, 1998; Am J Med Genet 70:67–73, 1997; Clin Dysmorphol 6:291–302, 1997 (Note: Beckwith-Wiedemann syndrome demonstrates dysmorphic ears, macroglossia, body asymmetry, midfacial vascular stains, visceromegaly with omphalocele, neonatal hypoglycemia, BUT NO MACROCEPHALY)

D-2 hydroxyglutaric aciduria – cardiomyopathy, hypotonia, cortical blindness, macrocephaly

Macrocephaly with cutis marmorata, hemangioma, and syndactyly syndrome – macrocephaly, hypotonia, hemihypertrophy, heman-

Cowden’s syndrome – macrocephaly (Lhermitte-Duclos disease – hamartomas of the cerebellum, kyphosis, pectus excavatum); keratosis punctate of the palms and soles; café au lait macules JAAD 68:189–209, 2013; AD 146:337–342, 2010; Ann Intern Med 58:136–142, 1963 Cowden’s disease (type 2 segmental Cowden’s disease) – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi (including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of the limbs, ballooning of the toes, bowel polyps, glomerulosclerosis, macropcephaly BJD 156:1089– 1090, 2007; Eur J Dermatol 17:133–136, 2007

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gioma, cutis marmorata telangiectatica congenita, internal arteriovenous malformations, syndactyly, joint laxity, hyperelastic skin, thickened subcutaneous tissue, developmental delay, short stature, hydrocephalus Ped Derm 16:235–237, 1999; Clin Dysmorphol 6:291–302, 1997 Majewski osteodysplastic primordial dwarfism type II Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome – macrocephaly, face and limb asymmetry, craniofacial abnormalities, joint laxity or soft skin, distal limb malformation; developmental delay Am J Med Genet C Semin Med Genet 163C:122–130, 2013; Nat Genet 44:934–940, 2012; Ped Derm 30:541–548, 2013 Neurofibromatosis type 1-like (NF-1-like) syndrome – autosomal dominant; multiple café au lait macules, axillary freckling, macrocephaly; Noonan-like dysmorphic changes; mutation in SPRED-1 gene; SJPRED-1 protein negatively regulates Rasmitogen-activated protein kinase (MAPK) Oncogene 34:637–638, 2015 Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – autosomal dominant; macrocephaly, frontal bossing, hypertelorism, cleft lip or palate, papules of the face, neck, and trunk, facial milia, lamellar calcification of the falx cerebri and tentorium cerebelli, cerebral cysts, calcifications of the brain, palmoplantar pits, mandibular keratocysts, skeletal anomalies, including enlarged mandibular coronoid, bifid ribs, kyphosis, spina bifida, polydactyly of the hands or feet, syndactyly; basal cell carcinomas; multiple eye anomalies – congenital cataract, microphthalmia, coloboma of the iris, choroid, and optic nerve; strabismus, nystagmus, keratin-filled cysts of the palpebral conjunctivae; also medulloblastomas, ovarian tumors (fibromas), mesenteric cysts, cardiac fibromas, fetal rhabdomyomas, astrocytomas, meningiomas, craniopharyngiomas, fibrosarcomas, ameloblastomas; renal anomalies; hypogonadotropic hypogonadism BJD 182:212–217, 2020; Ped Derm 32:141–142, 2015; BJD 165:30–34, 2011; AD 146:17–19, 2010; JAAD 39:853– 857, 1998; Dermatol Clin 13:113–125, 1995; JAAD 11:98–104, 1984; NEJM 262:908–912, 1960; linear unilateral nevoid basal cell nevus syndrome JAAD 50:489–494, 2004 Nevus sebaceus syndrome – PTEN mutation; hemimegalencephaly, dilated right ventricle, macrocephaly; association with Wilms’ tumor J Med Genet 40:e111, 2003; Ped Derm 29:15–23, 2012 NOMID (neonatal-onset multisystem inflammatory disease) – sporadic; generalized evanescent urticarial macules and papules (also includes CINCA (chronic infantile neurological cutaneous and articular syndrome) – cryopyrinopathy with mutation in CIAS1 (encodes cryopyrin); edematous papules and plaques, urticarial-like lesions in newborn, lesions, chronic aseptic meningitis, arthralgias of the knees and ankles with disabling deforming arthropathy with epiphyseal bone formation (osseous overgrowth), deafness, hepatosplenomegaly, anterior uveitis, vitreitis, papilledema, corneal stromal keratopathy; blindness, mental retardation; high-frequency hearing loss, developmental delay; recurrent fever and rash more severe in evening; headache, macrocephaly, cerebral atrophy; mutation in NALP3 (CIAS 1) which encodes cryopyrin JAAD 68:834–853, 2013; AD 144:392–402, 2008; AD 142:1591–1597, 2006; NEJM 355:581–592, 2006; JAAD 54:319–321, 2006; Ped Derm 22:222–226, 2005; AD 141:248–263, 2005; Arthritis Rheum 52:1283–1286, 2005; Noonan syndrome – macrocephaly, short stature, cardiovascular anomalies, ulerythema oophyrogenes; PTPNII; SOS1; RAF1; KRAS Am J Med Genet A 179:1628–1630, 2019; Am J Med Genet A 176:470–476, 2018 Oculo-ectodermal syndrome – macrocephaly, cutis aplasia, abnormal pigmentation, scalp nodules, corneal epibulbar dermoid cysts BJD 151:953–960, 2004

Osteogenesis imperfect – blue sclerae Clin Chim Acta 489:21–28, 2019 PHACES syndrome – large facial infantile hemangioma; posterior fossa malformations, cervicofacial hemangiomas, often segmental, arterial anomalies, cardiac defects, eye anomalies, and sternal clefting or supraumbilical raphe; Dandy-Walker malformation (posterior fossa cyst with hypoplasia of the cerebellar vermis; cystic dilatation of the fourth ventricle leading to hydrocephalus and increased head circumference) Ped Derm 26:730–734, 2009; Ped Derm 23:476–480, 2006; JAAD 58:81–87, 2008; JAAD 55:1072– 1074, 2006; Ped Derm 23:476–480, 2006; Clin Pediatr 44:747, 2005 Neuroradiology 16:82–84, 1978; association with hearing loss AD 146:1391–1396, 2010 Phylloid hypermelanosis – serpiginous hyperpigmentation with macrocephaly, frontal bossing, hypertelorism, internal strabismus, ear anomalies Ped Derm 31504–506, 2014 PTEN mutation syndromes (PTEN hamartoma syndrome) – capillary malformations, venous malformations, recurrent arteriovenous malformations, congenital nevi, pigmented penile or labial macules, café au lait macules, lipomas, megalencephaly, frontal bossing, downward slanting eyebrows and palpebral fissures, gastrointestinal polyps, thyroid neoplasms Ped Derm 28:466–467, 2011; AD 145:287–293, 2009 Russel-Silver syndrome – short stature, triangular-shaped face, clinodactyly of the fifth digit, macrocephaly Neonatal Netw 36:206–212, 2017; Epigenomics 8:563–580, 2016; Ped Derm 30:150–151, 2013 Simpson-Golabi-Behmel syndrome (bulldog syndrome – X-linked recessive; macroglossia, protruding jaw and tongue, widened nasal bridge, upturned nasal tip, hands/feet short, broad dysplastic nails, supernumerary nipples, hypotonia Sotos syndrome – cerebral gigantism with pre- and postnatal overgrowth, macrocephaly, dysmorphic face, frontal bossing, prominent chin, high hairline, downslanted palpebral fissures, mental retardation; NSD1 mutation (nuclear receptor-binding SET domain-containing protein) Hum Mutat 39:1226–1237, 2018; Ped Derm 25:122–125, 2008 Sturge-Weber syndrome Brain/dev 37:817–821, 2015 Thanatophoric dysplasia (short-limbed dwarfism) – large cranium, micromelia Ped Dev Pathol 16:160–167, 2013 Tuberous sclerosis Weaver’s syndrome – Am J Med Genet A 173:541–545, 2017 Wiedemann-Rautenstrauch (neonatal progeroid syndrome) – autosomal recessive; present at birth, generalized lipoatrophy, macrocephaly, sparse hair, premature aging, wide-open sutures, aged and triangular face with hypoplasia of facial bones, persistent fontanelles, prominent scalp veins, growth retardation, low-set ears, beak-shaped nose, neonatal teeth, slender limbs, large hands and feet with long fingers, joint contractures, large penis, pseudohydrocephalus, psychomotor retardation; osteosarcoma, thyroid carcinoma, melanoma; mutation in helicase BJD 164:245– 256, 2011; Ped Derm 22:75–78, 2005; J Med Genet 34:433–437, 1997; Am J Med Genet 35:91–94, 1990; Eur J Pediatr 130:65–70, 1979; Eur J Pediatr 124:101–111, 1977

MACRODACTYLY (ENLARGED DIGIT)  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Lupus erythematosus Rheumatoid arthritis AMB Rev Assoc Med Bras 25:141–142, 1979

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CONGENITAL LESIONS

INFLAMMATORY DISEASES

Clinodactyly, giant J Plast Surg Hand Surg 48:432–433, 2014 Congenital lipomatosis – adipose tissue malformation

Chronic granulomatous paronychia – pseudomegadactyly Dermatologica 169:86–87, 1984

Double digit

Osteoperiostitis

Duplication of the thumb JAAD 39:114–115, 1998 Isolated macrodactyly – PIK3CA mutation J Hand Surg Eur Vol 43:756–760, 2018

METABOLIC DISEASES

Monstrous congenital macrodactyly with syndactyly of the foot Acta Orthop Scand 69:201–202, 1998

Adrenal tumor with hemihypertrophy JAAD 33:154–155, 1995

Syndactyly J Hand Surg Eur Vol 44:216–218, 2019

DEGENERATIVE DISEASES Osteoarthritis

EXOGENOUS AGENTS Foreign body granuloma

INFECTIONS Brodie abscess – chronic abscess of bone surrounded by dense fibrous connective tissue and sclerotic bone Eikenella corrodens – cellulitis Clin Infect Dis 33:54–61, 2001; felon with fingertip necrosis Diabetes Care 19:1011–1013, 1996 Erysipelas Erysipeloid Felon Fusarium – red swollen toe with paronychia JAAD 65:235–237, 2011 Leprosy Mycobacterium tuberculosis – tuberculous dactylitis; lupus vulgaris (personal observation) Seal finger (speck finger) – Mycoplasma species (M. phocacerebrale and M. phocarhinis) Clin Infect Dis 27:1168–1170, 1998 Syphilis, congenital Tenosynovitis – acute suppurative tenosynovitis Warts

INFILTRATIVE DISEASES Amyloidosis Juvenile hyaline fibromatosis (infantile systemic hyalinosis) Ped Derm 23:458–464, 2006; JAAD 16:881–883, 1987 Sarcoidosis – sarcoid arthritis; sarcoid flexor tenosynovitis JAAD 55:S99–100, 2006 Self-healing juvenile cutaneous mucinosis – red nodules of the face, scalp, and hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973 Xanthoma disseminatum AD 121:1313–1317, 1985

Acromegaly Clubbing (Hippocratic fingers) (acropachy) JAAD 52:1020–1028, 2005; JAMA 286:341–347, 2001   Amyloid, liver abscess   Aortic aneurysm  Arsenic   Asbestosis JAAD 52:1020–1028, 2005  Asymmetric   Unidigital   Acquired reactive digital fibroma – subungual tumor with enlarged paronychium and macrodactyly JAAD 69:603–608, 2013   Differential diagnosis   Fibro-osseous pseudotumor of the digits; myofibroblastic proliferation in females; affects flexor digits and palms Chir Main 28:107–112, 2009; Cancer 58:2103–2109, 1986   Superficial acral fibromyxoma – subungual tumor Am J Surg Pathol 36:789–798, 2012   Cellular digital fibromas – resemble acquired digital fibrokeratoma and superficial acral fibromyxoma JAAD 69:603–608, 2013   Enchondroma JAAD 59:534–535, 2008   Epidermoid cyst    Felon    Acquired fibromatosis – personal observation    Gout    Median nerve injury   Osteoid osteoma    Sarcoid    Trauma   Unilateral     Aneurysm – left innominate artery    Axillary Pancoast tumors    Brachial arteriovenous aneurysm      Patent ductus arteriosus with pulmonary hypertension   Prolonged hemiplegia Bilateral clubbing   Bronchogenic carcinoma   Bronchiectasis, cysts   Carcinoma of the nasopharynx, colon, esophagus, stomach   Celiac sprue JAAD 52:1020–1028, 2005   CINCA syndrome JAAD 52:1020–1028, 2005  Cirrhosis   Crohn’s disease   Congestive heart failure   Cyanotic congenital heart disease JAAD 52:1020–1028, 2005   Cystic fibrosis JAAD 52:1020–1028, 2005   iarrhea, chronic   Down’s syndrome  Enchondroma JAAD 59:S34–35, 2008  Familial  Hemochromatosis    Hereditary – autosomal dominant   Hereditary mucoepithelial dysplasia

630 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1   HIV disease JAAD 52:1020–1028, 2005  Hyperparathyroidism   Hypertrophic pulmonary osteoarthropathy   Hypersensitivity pneumonitis JAAD 52:1020–1028, 2005   Hypervitaminosis A  Idiopathic   Idiopathic pulmonary fibrosis JAAD 52:1020–1028, 2005   Infective endocarditis JAAD 52:1020–1028, 2005   Inflammatory bowel disease JAAD 52:1020–1028, 2005   Juvenile polyposis coli JAAD 52:1020–1028, 2005   Laxative abuse SMJ 76:1071, 1983; Lancet 2:947, 1978   Liver disease JAAD 52:1020–1028, 2005    Lung abscess, empyema   Lupus erythematosus BJD 89:533–535, 1973  Lymphoma JAAD 52:1020–1028, 2005  Malabsorption  Malaria  Malnutrition   Marfan’s syndrome – pseudoclubbing   Marie-Bamberger syndrome   Mesothelioma JAAD 52:1020–1028, 2005   Nasopharyngeal carcinoma JAAD 52:1020–1028, 2005   Parasitic bacillary dysentery JAAD 52:1020–1028, 2005   Phosphorus toxicity   Pleural tumors JAAD 52:1020–1028, 2005   POEMS syndrome JAAD 52:1020–1028, 2005   Polycythemia  Psoriatic onychopachydermoperiostitis BJD 143:901–902, 2000; Rev Rheum Mal Osteoartic 56:579–582, 1989  Pulmonary arteriovenous malformation JAAD 52:1020–1028, 2005  Pycnodysostosis – pseudoclubbing (acro-osteolysis) Br Med J iii:712–714, 1967   Sarcoidosis JAAD 52:1020–1028, 2005  Sprue  Syringomyelia    Systemic lupus erythematosus   Thymoma, malignant  Thyroid disease – myxedema, Graves’ disease (thyroid acropachy) JAAD 26:885–902, 1992; Med Clin NA 52:393–395, 1968; JAAD 52:1020–1028, 2005;  Transpulmonary right to left shunts Clin Exp Rheumatol 10(Suppl 7):23–25, 1992 Tuberculosis JAAD 52:1020–1028, 2005   Ulcerative colitis   Venous stasis JAAD 52:1020–1028, 2005  X-linked reticulate pigmentary disorder with systemic manifestations (familial cutaneous amyloidosis) (Partington syndrome II) – X-linked; rare; Xp21–22; boys with generalized reticulated muddy brown pigmentation (dyschromatosis) with hypopigmented corneal dystrophy (dyskeratosis), coarse unruly hair, unswept eyebrows, silvery hair, hypohidrosis, recurrent pneumonia with chronic obstructive disease, clubbing; failure to thrive, female carriers with linear macular nevoid Blaschkoesque hyperpigmentation Ped Derm 22:122–126, 2005; Semin Cut Med Surg 16:72–80, 1997; Am J Med Gen 10:65:1981   Gouty tophus   Mucopolysaccharidoses – Sly syndrome, Hurler’s syndrome  Multiple sulfatase deficiency – broad thumbs, ichthyosis, gargoylism Ped Derm 18:388–392, 2001   Tuberous xanthomas JAAD 13:1–30, 1986

NEOPLASTIC DISEASES Acquired reactive digital fibroma – macrodactyly of the thumb and great toe JAAD 69:603–608, 2013 Aggressive digital papillary adenoma (adenocarcinoma) Cutis 72:145–147, 2003; Cutis 69:179–182, 2002; Dermatol Surg 26:580–583, 2000; AD 120:1612, 1984; JAAD 23:331–334, 1990 Chondrosarcoma Connective tissue nevi JAAD 33:154–155, 1995 Digital myxoid cyst – clubbed finger BJD 146:125–128, 2002; AD 132:225–228, 1996 Epidermal nevus JAAD 33:154–155, 1995 Epidermoid cyst – intraosseous epidermoid cyst (epidermoid cyst of the distal phalanx; primary bone epidermoid cyst) BJD 145:366– 368, 2001; Can Med Ass 87:770, 1962; Am J Surg 85:771–774, 1953; Am J Surg 85:327–334, 1953 Epithelioid sarcoma JAAD 26:302–305, 1992 Exostosis JAAD 19:132, 1988 Fibromatosis – localized digital fibromatosis Acta DV 74:386–387, 1994; Clin Exp Dermatol 16:121–123, 1991 Fibro-osseous pseudotumor of the digits BJD 144:1274–1275, 2001 Fibrosarcoma Fibrous hamartoma Ped Derm 17:270–276, 2000; Garlic clove tumor – acquired periungual fibrokeratoma Cutis 46:118–124, 1990 Giant cell tumor of the tendon sheath BJD 146:125–128, 2002 Glomus tumor Granular cell tumor – tip of the great toe Ped Derm 24:235–237, 2007 Growth promoting neoplasm – adrenocortical tumor, testicular tumor, Wilms’ tumor Ped Derm 17:270–276, 2000 Infantile desmoid-type fibromatosis Ped Derm 12:149–151, 1995 Infantile digital fibromatosis Ped Derm 24:280–284, 2007 Intraosseous chondroid syringoma JAAD 30:374–378, 1994 Kaposi’s sarcoma – epidemic Dermatol Clin 24:509–520, 2006; endemic African Kaposi’s sarcoma JAAD 22:1237–1250, 1990 Lipofibromatous hamartoma J Hand Surg 13:67–75, 1988; lipofibromatous hamartoma of the median nerve Ped Derm 15:378–380, 1998; congenital lipofibromatosis Foot Ankle 12:40– 46, 1991; hyperostotic macrodactyly and lipofibromatous hamartoma of the median nerve Chir Main 18:261–271, 1999; fibrolipomatous hamartoma of the nerve (nerve territory-oriented macrodactyly) (macrodystrophia lipomatosa) Skeletal Radiol 24:296–297, 1995 Lipofibromatous hamartoma (intraneural tumor) (macrodactyly) (third decade (fibrolipomatous hamartoma of the nerve) (neural fibrolipoma) (neurofibrolipomatous hamartoma) – macrodactyly and syndactyly J Clin Orthop Trauma 10:1077–1081, 2019; JAAD 70:736–742, 2014; Ped Derm 31:298–304, 2014; JAAD 53:528– 529, 2005; Ped Derm 17:270–276, 2000; AD 135:707–712, 1999 Lipomas BJD 146:125–128, 2002; J Foot Ankle Surg 38:223–226, 1999; J Bone Surg Am 70:128–130, 1998; subungual lipoma BJD 149:418, 2003 Lymphoma – cutaneous T-cell lymphoma JAAD 59:154–157, 2008 Macrodystrophia lipomatosa (hamartomatous macrodactyly) (localized gigantism) J Clin Imaging Sci Feb 27, 2019; Ped Derm 17:270–276, 2000;

Macrodactyly (Enlarged Digit)

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Melanoma, JAAD 70:748–762, 2014; subungual Caputo, 2000, p. 94

SYNDROMES

Metastases – especially bronchogenic carcinoma JAAD 31:259– 263, 1994

Aase-Smith syndrome II – triphalangeal thumbs J Pediatr 74:471– 474, 1969

Myxochondroma – clubbed finger Polyclinic (Prat)60:1571–1575, 1953 Myxoid cyst BJD 146:125–128, 2002 Neurinoma Neurofibroma, including plexiform neurofibroma J Pediatr Orthop 6:489–492, 1986; subungual BJD 146:125–128, 2002 Onychoblastoma (hamartoma of the nail unit) BJD 152:1077–1078, 2005 Osteochondroma Chir Main 18:261–271, 1999 Osteocystoma Osteoid osteoma J Foot Ankle Surg 58:586–590, 2019; J Hand Surg 12B:387–390, 1987 Osteogenic sarcoma Osteoma – clubbed finger Ann DV 129:1172–1173, 2002 Osteophytes Foot Ankle Int 17:283–285, 1996 Pacinian neuroma J Clin Diag Res 9:PD22–23, 2015 Perineuroma (subungual) BJD 146:125–128, 2002 Plexiform schwannoma (neurilemmoma) J Hand Surg 21:707–710, 1996 Recurrent digital fibrous tumors of childhood Spindle cell hemangioendothelioma – multiple subcutaneous nodules; palmar giant cobblestoning; hypertrophy of the hand Cutis 79:125–128, 2007

PRIMARY CUTANEOUS DISEASES Digital gigantism (double digit) (idiopathic localized gigantism JAAD 61:621–628, 2009; JAAD 33:154–155, 1995 Epidermolysis bullosa, junctional – letalis; atrophicans generalisata gravis, Herlitz type – extensive blistering and erosions at birth; bulbous finger tips with crusting and erosions Erythema elevatum diutinum

Acrocallosal syndrome – broad halluces Helv Paediatr Acta 34:141–146, 1979 Acrofacial dysostosis – triphalangeal thumbs Am J Med Genet 14:225–229, 1983 ADULT (acro-dermato-ungual-lacrimal-tooth) syndrome – closely resemble EEC syndrome; hypodontia, ectrodactyly, obstruction of lacrimal ducts, onychodysplasia, freckling Am J Med Genet 45:642–648, 1993 Apert syndrome – acrocephalopolysyndactyly; broad halluces Birth Defects 11:137–189, 1975 Auro-digital-anal syndrome – broad thumbs Bannayan-Zonana-Ruvalcaba syndrome – macrodactyly, subcutaneous lipomatosis, megalencephaly Acta Pathol Jpn 36:269–277, 1986; Ped Derm 17:270–276, 2000 Beckwith-Wiedemann syndrome Carpenter syndrome (acrocephalosyndactyly type II) – broad halluces Am J Dis Child 124:716–718, 1972 CHILD syndrome – X-linked dominant; linear hyperkeratosis with brownish scaling of fingers and toes AD 142:348–351, 2006; linear hyperkeratotic plaques of the feet (unilateral inflammatory ichthyosiform nevus) with spontaneous involution; strawberry-like papillomatous lesions of toes; macrodactyly; ptychotropism, shortening, and absence of limbs, short stature; ipsilateral involvement of the bones, lung, kidney, heart, brain; epiphyseal stippling (chondrodysplasia punctata); short stature, scoliosis, clefting of hand or foot, hexadactyly; lateralization and mutations in NSDHL gene which encodes 3-beta hydroxysteroid dehydrogenase JAAD 63:1–22, 2010; BJD 161:714–715, 2009 CLOVE syndrome – capillary, venous, and mixed vascular malformations, epidermal nevi, congenital lipomatous overgrowth; hemihypertrophy (milder than that of Proteus syndrome); ballooning of big toes, symmetrically overgrown feet; wrinkling of palms and soles; severe central nervous system involvement Ped Derm 28:215–216, 2011; Ped Derm 27:311–312, 2010; Am J Med Genet 143A:2944–2958, 2007

Familial macrodactyly Arch Ped Adolescent Med 148:1309–1310, 1994; mother to daughter J Pods 5:650, 1935; siblings Arch Neurol and Psych 14:824, 1925

Craniodysostosis with extremity bands – personal observation

Hyperostotic macrodactyly J Hand Surg 13:544–548, 1988

Cowden’s disease (type 2 segmental Cowden’s disease) – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi (including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of limbs, ballooning of toes, bowel polyps, glomerulosclerosis, macropcephaly BJD 156:1089–1090, 2007; Eur J Dermatol 17:133–136, 2007

Idiopathic macronychia and macrodactyly Ped Derm 17:270–276, 2000 Macrodactylia simplex congenita – static type, digit enlarged at birth, does not grow – usually a form of lipomatosis Ped Derm 17:270–276, 2000; S Ar Med J 70:755–758, 1986 Pachydermodactyly – benign fibromatosis of fingers of young men Clin Exp Dermatol 28:674–675,2003; AD 111:524, 1975; fusiform swelling of fingers AD 141:1035–1040, 2005 Primary macrodactyly – personal observation Progressive macrodactyly J Foot Ankle Surg 38:143–146, 1999 Psoriatic onychopachydermoperiostitis BJD 153:858–859, 2005

Craniofrontonasal dysplasia – broad halluces Birth Defects 15:85–89, 1979

Del(4p) syndrome (Wolf-Hirschhorn syndrome) – broad halluces Am J Med Genet 21:351–358, 1985 Del(7p) syndrome – broad halluces Hum Genet 35:117–123, 1976 Dysplasia epiphysealis hemimelica J Hand Surg (Br) 10:249–250, 1985

Segmental fibrous dysplasia Genet Couns 10:373–376, 1999

Ectrodactyly-ectodermal dysplasia cleft lip/palate (lobster claw deformity) (EEC syndrome) – peg-shaped teeth Clin Dysmorphol 5:115–127, 1996; JAAD 29:347–350, 1993

Tarsomegaly

Facio-digito-genital syndrome – syndactyly

Racquet nails

632

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Familial mandibuloacral dysplasia (craniomandibular dermatodysostosis) – atrophy of the skin over the hands and feet with club-shaped terminal phalanges and acro-osteolysis, mandibular dysplasia, delayed cranial suture closure, short stature, prominent eyes, and sharp nose BJD 105:719–723, 1981; Birth Defects x:99–105, 1974 Femoral hypoplasia-unusual facies syndrome – broad halluces Syndromes of the Head and Neck, p. 31, 1990 FG syndrome – broad halluces Am J Med Genet 19:379–382, 1984 Fibrolipomatosis JAAD 61:621–628, 2009 Frontonasal malformation – broad halluces Clin Genet 10:214–217, 1976 Gardner’s syndrome – autosomal dominant; osteomas of skull, epidermoid cysts, and fibromas before age 10; polyposis of the colon Goltz’s syndrome Gorham’s syndrome Greig cephalopolysyndactyly syndrome (frontodigital syndrome) – broad halluces Clin Genet 24:257–265, 1983 Incontinentia pigmenti – double nail with dorsalization of plantar skin (dorsal dimelia); enlarged digit JAMA Derm 149:762–763, 2013 Jackson-Weiss syndrome – broad halluces J Pediatr 88:963–968, 1976 Kasabach-Merritt syndrome JAAD 29:117–119, 1993 Keipert syndrome (broad terminal phalanges and facial abnormalities) Aust Paediatr J 9:10–13, 1973 Klippel-Trenaunay-Weber syndrome – port wine stain with lymphatic malformation and lymphedema JAAD 65:893–906, 2011; JAAD 61:621–628, 2009; Ped Derm 17:270–276, 2000; Cutis 60:127–132, 1997; J Bone Joint Surg Am 73:1537–1546, 1991 LADD syndrome – triphalangeal thumbs Eur J Pediatr 146:536–537, 1987 Larsen syndrome Syndromes of the Head and Neck, pp. 722–724, 1990 Macrocephaly-cutis marmorata syndrome JAAD 61:621–628, 2009 Macrocephaly-CMTC (cutis marmorata telangiectatica congenita syndrome) – renamed “macrocephaly-capillary malformation syndrome” now renamed “megalencephaly capillary malformation syndrome” – macrocephalic neonatal hypotonia and developmental delay; frontal bossing, segmental overgrowth, syndactyly, asymmetry, distended linear and serpiginous abdominal wall veins, patchy reticulated or telangiectatic port wine stain (vascular stain) without atrophy; fading of port wine stain in first year; telangiectasias of the face and ears; midline reticulated facial nevus flammeus (capillary malformation) (vascular stains), central facial salmon patches; hydrocephalus, skin and joint hypermobility, hyperelastic skin, thickened subcutaneous tissue, polydactyly, 2–3 toe syndactyly, post-axial polydactyly, hydrocephalus, frontal bossing, hemihypertrophy with segmental overgrowth; enlarged hand (macrmano); connective tissue defects; PIK3CA mutations BJD 175:810–814, 2016; JAAD 65:893–906, 2011; Ped Derm 26:342– 346, 2009; AD 145:287–293, 2009; JAAD 58:697–702, 2008; Ped Derm 24:555–556, 2007; JAAD 56:541–564, 2007; Ped Derm 16:235–237, 1999; Genet Couns 9:245–253, 1998; Am J Med Genet 70:67–73, 1997; Clin Dysmorphol 6:291–302, 1997; (Note: Beckwith-Wiedemann syndrome demonstrates dysmorphic ears, macroglossia, body asymmetry, midfacial vascular stains, visceromegaly with omphalocele, neonatal hypoglycemia, BUT NO MACROCEPHALY) Macrodystrophia lipomatosa progressiva – dynamic type; overgrowth of fatty tissue occurs and digits enlarge disproportionately

Arch Orthop Traum Surg 110:220–221, 1991; A J Roentgenol 128:101–105, 1977 Maffucci’s syndrome (enchondromatosis) – enchondromas and multiple venous malformations; spindle cell hemangioendothelioma; oral and intra-abdominal venous and lymphatic anomalies; short stature, shortened long bones with pathologic fractures; enchondromas undergo sarcomatous change in 30–40%; breast, ovarian, pancreatic, parathyroid, pituitary tumors J Pediatr 167:1157–1159, 2015; JAAD 56:541–564, 2007; Ped Derm 17:270–276, 2000 Maghazaji syndrome Dev Med Child Neurol 25:798–800, 1983 Multiple exostoses syndrome JAAD 25:333–335, 1991 Multiple symmetric lipomatosis of the hands Clin Exp Dermatol 14:58–59, 1989 Munchmeyer’s syndrome – broad thumb; myositis, ossificans progressive Ethiop J Health Sci 28:513–516, 2018; Dentomaxillofac Radiol 43(5)20140022, 2014 Neurofibromatosis Am J Pathol 261:1059–1083, 1950; Ped Derm 17:270–276, 2000; JAAD 43:1136–1137, 2000 Nevus comedonicus syndrome Ped Derm 15:304–306, 1998 Oculo-dento-digital dysplasia Ollier’s disease – multiple enchondromata Ped Derm 12:55–58, 1995; Ped Derm 17:270–276, 2000 Oral-facial-digital syndromes (types 1, 2) – syndactyly Oto-palato-digital syndrome – broad thumb Birth Defects 5:43–44, 1969; Am J Dis Child 113:214–221, 1967 Pachydermodactyly JAAD 27:303–305, 1992; distal pachydermodactyly (acquired digital fibrosis) JAAD 38:359–362, 1998; fusiform swelling of fingers AD 141:1035–1040, 2005 Pachydermoperiostosis – primary (Touraine-Solente-Gole syndrome) (autosomal dominant) – clubbing BJD 170:1187–1194, 2014; folds and furrows of the forehead and cheeks, heavy thick eyelids, cutis verticis gyrata; thick skin of the hands and feet; palmoplantar hyperhidrosis; enlarged hands JAAD 31:947–953, 1994; Medicine 70:208–214, 1991; AD 124:1831–1834, 1988; secondary – pulmonary disease, lung cancer, carcinoma of the stomach, esophagus, thymus Pfeiffer syndrome Birth Defects 11:137–189, 1975 Proteus syndrome – macrodactyly, hemihypertrophy, lipomas, lymphangiomas, epidermal nevi, decreased subcutaneous fat, superficial venous prominence, palmar or plantar cerebriform connective tissue nevi, cutis marmorata, exostoses, macrocephaly, asymmetric growth somatic mosaic mutation of AKT1 J Drugs in Dermatol 12:586–587, 2013; NEJM 365:611– 619, 2011; AD 140:947–953, 2004; AD 137:219–224, 2001; JAAD 25:377–383, 1991; Ped Derm 17:270–276, 2000; Ped Derm 11:222–226, 1994 Robinson’s syndrome – nail dystrophy-deafness syndrome – polysyndactyly Minerva Ped 36:421–424, 1984 Rubinstein-Taybi syndrome – broad thumbs BJD 171:615–621, 2014; JAAD 46:161–183, 2002; JAAD 46:159, 2002; Ped Derm 19:177–179, 2002; Ped Derm 11:21–25, 1994; mental deficiency, small head, broad thumbs and great toes, beaked nose, malformed low-set ears, capillary nevus of the forehead, hypertrichosis of the back and eyebrows, multiple keloids, cardiac defects Cutis 57:346–348, 1996; Am J Dis Child 105:588–608, 1963 Sly syndrome Saethre-Chotzen syndrome – broad halluces J Pediatr 76:928–930, 1970 Temtamy syndrome J Ped 89:924–927

Malodorous Skin Conditions Townes-Brocks syndrome – triphalangeal thumbs Dysmorphol Clin Genet 2:104–108, 1988

MALODOROUS SKIN CONDITIONS

Trichorhinophalangeal syndrome Gene Review April 20, 2017

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION

Trisomy 21 Tuberous sclerosis – Koenen’s tumors, periosteal hyperplasia, fibrous plaques of the hand and fingers Ped Derm 18:364–365, 2001; Ped Derm 17:463–465, 2000; Skeletal Radiol 28:116–118, 1999; J R Soc Med 87:419–420, 1994; subcutaneous fibrous hamartomas and macrodactyly Skeletal Radiol 46:1293–1296, 2017 Weaver syndrome J Med Genet 17:174–178, 1980

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Giant disseminated verrucosis (HPV2) (giant verrucous claw hands and feet) associated with idiopathic CD4 lymphopenia AD 146:69– 73, 2010 Pemphigus vegetans AD 123:396–397, 1987 Pemphigus vulgaris – oral ulcers

Zunich syndrome – broad second toes Ped Derm 13:363–371, 1996

EXOGENOUS AGENTS TRAUMA

Bromoderma

Chilblains – personal observation

Methamphetamine abuse JAAD 69:135–142, 2013

Physical trauma

Podoconiosis – non-infectious tropical lymphedema, lymphedema below the knee; offensive odor due to edema, hyperkeratosis, and fissures

VASCULAR DISORDERS Aneurysm – cirsoid aneurysm (arteriovenous fistula) – blue non-pulsatile nodules of nail fold with macrodactyly BJD 115:361– 366, 1986 Angiodysplasia, localized Ann Med Interne (Paris) 140:237–239, 1989 Arteriovenous malformation – congenital swelling of the toe Ped Derm 31:103–104, 2014; JAAD 56:353–370, 2007 Achenbach’s syndrome (paroxysmal hematoma of the fingers) – sudden onset of localized edema and pain; associated with a thrombus and/or hematoma JAAD 56:493, 2007; J Hand Surg 27:391–393, 2002; Hautarzt 41:270–271, 1990 Blue rubber bleb nevus syndrome AD 129:1505–1509, 1993 Hemangioma, congenital, subungual – pseudoclubbing JAAD 53:S123–126, 2005 Lymphangiosarcoma Lymphatic malformation Lymphedema, congenital (Milroy’s disease) or acquired – chronic JAAD 61:621–628, 2009; Ped Derm 17:270–276, 2000 Parkes-Weber syndrome – arteriovenous malformation with multiple arteriovenous fistulae along the extremity with limb (usually leg) overgrowth; arteriovenous shunting; cutaneous red stain; lymphedema; high-output congestive heart failure, hypertrophied digits with severe deformity; red foot; hypertrophy with pulsatile dilated veins and arteries, palpable thrill, giant arteriovenous malformation NEJM 371:2114, 2014; JAAD 56:541–564, 2007; Curr Prob in Dermatol 13:249–300, 2002; BJD 19:231–235, 1907 Retiform hemangioendothelioma JAAD 38:143–175, 1998; macrodactyly with swelling of the distal finger JAAD 65:233–235, 2011 Spindle cell hemangioma – enlarged thumb with vascular nodules BJD 179:976–977, 2018 Sturge-Weber syndrome JAAD 61:621–628, 2009 Vascular hamartoma Ped Derm 17:270–276, 2000; Vascular malformation – Klippel-Trenaunay-Weber Ped Derm 17:270–276, 2000 Venous malformation JAAD 56:353–370, 2007; of toe Ped Derm 26:399–404, 2009; enlarged hand, hemihypertrophy, mountain range changes BJD 157:558–562, 2007

INFECTIONS AND INFESTATIONS Amebiasis (Entamoeba histolytica) – nasal destruction with malodorous ulcer with gray-white necrotic base Cutis 90:310–314, 2012 Candidal intertrigo Chronic osteomyelitis and non-healing scalp ulcer Ann Derm 23(suppl3):S364–367, 2011 Glanders (farcy) (Burkholderia (Pseudomonas) mallei) – cellulitis which ulcerates with purulent foul-smelling discharge, regional lymphatics become abscesses; nasal and palatal necrosis and destruction; metastatic papules, pustules, bullae over joints and face, then ulcerate; deep abscesses with sinus tracts occur; polyarthritis, meningitis, pneumonia JAAD 54:559–578, 2006 Gram-negative web space infection Necrotizing fasciitis, including Fournier’s gangrene Pitted keratolysis (“toxic sock syndrome”) Dermatol Reports Feb 7, 2014; Am Fam Physician 57:2215–2216, 1998 Pseudomonas contamination of leg ulcers Stink bugs (Pentatomidae) – red plaques and vesicles JAAD 67:331–344, 2012 Trench mouth

INFLAMMATORY DISORDERS Hidradenitis suppurativa Postgrad Med J 90:216–221, 2014

NEOPLASMS Epidermal nevus syndrome (Schimmelpenning-Feuerstein-Mims syndrome) Am J Dermatopathol 34:671, 2012 Epidermoid cyst contents Epidermolytic hyperkeratosis Epithelioma cuniculatum (verrucous carcinoma of the foot) Malignant fungating tumor – ulcerated breast cancer, squamous cell carcinoma, basal cell carcinoma Dermatol Therapy, March 5, 2015; J Cut Aesthet Surg 5:12–19, 2012; J Skin Cancer 2011:392151

634 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Marjolin’s ulcer (squamous cell carcinoma) in chronic osteomyelitis Rev Chir Orthop Reparatrice Appar Mot 93:63–71, 2007

Camurati-Engelmann disease type II – progressive diaphyseal dysplasia with striation of bones; waddling gait, muscle weakness, intense leg pain J Med Genet 107:5–11, 2002

PRIMARY CUTANEOUS DISEASES

Cataract, microcornea, dental anomalies Ophthalmology 86(10):1764–1793, 1979

Bromhidrosis Clinics in Dermatol 33:483–491, 2015

Cerebro-oculo-renal syndrome of Bhaskar Ophthalmology 86(10):1764–1793, 1979

Darier’s disease Hailey-Hailey disease Mal de Meleda – autosomal dominant, autosomal recessive; diffuse PPK; progressive and transgrediens with acral erythema in glove-like distribution; perioral erythema and hyperkeratosis; hyperkeratotic plaques over joints, malodorous hyperhidrosis; ichthyosis; knuckle pads; pseudo-ainhum with amputation; lingua plicata, brachydactyly, syndactyly, hairy palms and soles, nail anomalies, lichenoid plaques, high-arched palate, left-handedness; mild ichthyosis; mutations in ARS component B gene (SLURP1) Cutis 93:193–198, 2014; BJD 168:1372–1374, 2013; AD 147:748– 750, 2011; BJD 160:160:878–880, 2009; AD 144:375–379, 2008; JID 120:351–355, 2003; Dermatology 203:7–13, 2001; AD 136:1247–1252, 2000; J Dermatol 27:664–668, 2000; BJD 128:207–212, 1993; Dermatologica 171:30–37, 1985; Arch Dermatol Syphilol 42:163–174, 1898 Poor hygiene

SYNDROMES Cardio-facio-cutaneous syndrome – bromhidrosis, abnormal hair, sparse eyebrows and lashes, ichthyosiform hyperkeratosis, widespread keratosis pilaris-like papules, seborrheic dermatitis, hemangiomas, nail dystrophy, lymphedema; characteristic facies with large head, high forehead, bitemporal constriction, antimongoloid slant of palpebral fissures, depressed nasal bridge, low-set ears with thick helices psychomotor and growth retardation; pulmonic stenosis and atrial septal defects JAAD 28:815–819, 1993 Pachydermoperiostosis Pachyonychia congenita

TOXINS Arsenic poisoning – garlicky odor, severe diarrhea NEJM 370:1542– 1550, 2014

VASCULAR DISORDERS Diabetic foot ulcers J Wound Care 25:438–442, 2016 Elephantiasis nostras verrucosa (mossy foot) J Am Pod Med Assoc 98:66–69, 2008

Cohen syndrome – mental retardation, congenital hypotonia, microcephaly, pleasant affect, micrognathia, open mouth with prominent incisors Congenital contractural arachnodactyly – joint contractures (elbows and knees), crumpled ears Clinics in Dermatol 24:521–533, 2006 Cotlier-Reinglass syndrome Ophthalmology 86(10):1764–1793, 1979 Cowden’s syndrome Craniostenosis Cutis laxa – congenital cutis laxa type V with Marfanoid habitus Ann DV 117:823–824, 1990 Cytoplasmic body and mitochondrial DNA deletion – Marfanoid habitus and perceptive hearing loss J Neurol Sci 99:291–300, 1990 Diverticulosis, hernia, retinal detachment Ophthalmology 86(10):1764–1793, 1979 Ehlers-Danlos syndrome type VIa JID 103:47S–52S, 1994; type VI – blue sclerae, scleral fragility, joint hypermobility, skin hyperextensibility, easy bruising, atrophic scarring, Marfanoid habitus, scoliosis, neonatal hypotonia, arterial dissection; type VIII – autosomal dominant; skin fragility, abnormal scarring, severe early periodontitis with loss of adult dentition by the end of the third decade; cigarette paper scars of the shin; Marfanoid habitus (tall, long limbs, arachnodactyly); triangular face, prominent eyes, thin nose, prematurely aged appearance, thin skin with prominent veins, no joint hypermobility, easy bruising, blue sclerae BJD 158:825– 830, 2008; JAAD 55:S41–45, 2006 Ehlers-Danlos type VIb Familial Marfanoid habitus Am J Med Genet 62:417–426, 1996 Familial mitral valve prolapse syndrome Am J Med Genet 62:417– 426, 1996 Familial myopathy with Marfanoid features and multicores Aust N Z J Med 14:495–499, 1984 Goodman campylodactyly syndrome B Ophthalmology 86(10):1764–1793, 1979 Homocystinuria (cystathionine-beta synthase deficiency) – Marfanoid habitus, malar rash, larger facial pores, livedo reticularis, tissue paper scars, sparse fine hair, superficial thrombophlebitis NEJM 375:1069–1077, 2016; Clinics in Dermatol 24:521–533, 2006; JAAD 46:161–183, 2002; JAAD 40:279–281, 1999 Klinefelter syndrome Ophthalmology 86(10):1764–1793, 1979

MARFANOID FEATURES SYNDROMES Alpha-2-deficient collagen disease Klin Wschr 52:906–912, 1974 Beals-Hecht syndrome (congenital contractural arachnodactyly) – autosomal dominant; crumpled ears, arachnodactyly with congenital joint contractures, confused with Marfan’s syndrome but no cardiovascular abnormalities Am J Med Genet 25:763–773, 1986; J Bone Joint Surg 53:987–993, 1971

Klippel-Trenaunay syndrome Loeys-Dietz syndrome – joint hypermobility, thin skin with prominent veins, Marfanoid body habitus, triangular delicate face, hypertelorism, bifid uvula or cleft palate, velvety and translucent skin, clubbed feet, no ectopia lentis; arterial dissection and rupture, prominent eyes, blue sclerae, aortic aneurysms, generalized arterial tortuosity with increased arterial dissections, often small arterial size type I and II TGF beta 3 Am J Med Genetic A Feb 5, 2020; JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005 L-looped transposition of the great arteries with Marfanoid habitus Cureus Aug 18, 2019

Masses of the Head and Neck Lujan-Fryns syndrome – X-linked; hypernasal voice, large head and long narrow face; mental retardation with Marfanoid habitus Clin Med Insights Case Rep 9:115–118, 2016; Am J Med Genet 119A:363–366, 2003 Marfan’s syndrome – long extremities, arachnodactyly, joint contractures, skeletal, ocular, cardiovascular defects Am J Med Genet 62:417–426, 1996; Int J Derm 28:291–299, 1989; mutations of fibrillin 1, type II TGF beta receptor JAAD 55:S41–45, 2006 Marfan’s syndrome with neurogenic muscle atrophy Kurume Med J 38:275–279, 1991 Marfanoid body habitus with crystalline lens subluxation, acute exophthalmos with intraocular hemorrhage and coma Medicina (Buenos Aires) 52:563–569, 1992 Marfanoid body habitus with acquired tracheobronchomegaly Chest 98:491–492, 1990 Marfanoid body habitus – with excessive hyperextensibility (Ehlers-­Danlos syndrome type VIB) Am J Med Genet 36:269–272, 1990; Nippon Naika Gakkai Zasshi 77:499–505, 1988 Marfanoid body habitus with situs inversus Am J Med Genet 127A:310–312, 2004 Marfanoid habitus with long face, hypotelorism; long, thin nose; long, thin hands and feet; language and learning disabilities Am J Med Genet A 143A:3137–3139, 2007 Marfanoid features, visceral diverticula, diaphragmatic eventration Arch Dis Child 75:247–248, 1996 Marfanoid hypermobility syndrome – marked joint hypermobility, cutaneous hyperextensibility, aortic dissection, no easy bruising JAAD 55:S41–45, 2006; microcephaly, mental retardation, focal glomerulonephritis Clin Dysmorphol 1:111–113, 1992; Ann Int Med 71:349–352, 1969 Marfanoid phenotype, congenital contractures with ocular and cardiovascular anomalies, cerebral white matter hypoplasia, and spinal axonopathy Eur J Pediatr 143:228–231, 1985 MASS phenotype – myopia, mitral valve prolapse, mild aortic dilatation, skin striae, atrophic skin patches (anetodermas), slender habitus, loss of subcutaneous fat, skeletal involvement JAMADerm 150:885–889, 2014; Am J Med Genet 62:417–426, 1996; JAMADerm 262:523–528, 1989 Megaduodenum megacystis Ophthalmology 86(10):1764–1793, 1979; Arch Surg 96:549–553, 1968 Mental retardation, X-linked, Snyder-Robinson type Clin Pediatr 8:669–674, 1969 Methylmalonic aciduria and homocystinuria, cb1C type Biochem Med 4:500–515, 1970 Mirhosseini syndrome Ophthalmology 86(10):1764–1793, 1979 Multifocal Langerhans cell granulomatosis and diabetes insipidus with Marfanoid habitus J Assoc Physicians India 36:665–667, 1988 Multiple endocrine neoplasia, type I – Marfanoid habitus, optic atrophy MEN IIA – Sipple syndrome Multiple mucosal neuroma syndrome (MEN IIB) (Gorlin’s syndrome) (Wagenmann-Froboese syndrome) – autosomal dominant; skin-colored papules of the cheeks and mucosal neuromas of the lips, tongue, oral mucosa (buccal mucosa, gingiva, palate, pharynx); conjunctival nodules; medullary carcinoma of the thyroid; adrenal medulla pheochromocytoma; eversion of the lips and eyelids, widened nasal base; Marfanoid features; RET proto-oncogene JAMA Derm 152:939–940, 2016; NEJM 364:870, 2011; Ped Derm 25:477–478, 2008; JAAD 55:341–344, 2006; Curr Prob Derm 14:41–70, 2002; Am J Med 31:163–166, 1961; thickened eyelid margins AD 139:1647–1652, 2003; JAAD 42:939–969, 2000

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MEN type III – Froboese’ syndrome Myotonic dystrophy Ophthalmology 86(10):1764–1793, 1979 Nemaline myopathy Ophthalmology 86(10):1764–1793, 1979 Nerve deafness, eye anomalies, and Marfanoid habitus – autosomal dominant Birth Defects:Original Article Series.07(4):137–139, 1971 Nevoid basal cell carcinoma syndrome JAAD 11:98–104, 1984 Novel fibrosing disorder – subcutaneous fibrotic nodules, progressive distal joint contractures, Marfanoid stature, forehead nodules, skin tightening (sclerodermoid changes), palmoplantar nodules, nodules of elbows and knees, linear arrays of nodules later in course; differentiate from Marfan’s syndrome, congenital contractural arachnodactyly, Winchester syndrome, multicentric osteolysis nodulosis and arthropathy (MONA) syndrome BJD 163:1102–1115, 2010 Pachydermoperiostosis, cryptorchidism, and Marfanoid appearance Arch Belg Dermatol Syphiligr 23(1):121–135, 1967 Peculiar facies and Marfanoid habitus with psychomotor retardation Clin Genet 25:187–190, 1984 Perrault syndrome – gonadal dysgenesis, progressive sensorineural deafness, Marfanoid body proportions and skeletal features; normal female karyotype Clin Dysmorphol 26:200–204, 2017 Shprintzen-Goldberg syndrome – Marfanoid features and craniostenosis (craniosynostosis), mental retardation Australas Med J 7:51–57, 2014; Am J Med Genet 76:202–212, 1998; J Craniofac Genet Dev Biol 2:65–74, 1982; without mental retardation Clin Dysmorphol 2:220–224, 1993 Sickle cell anemia Stickler syndrome (hereditary arthroophthalmopathy) (WagnerStickler syndrome) (dystrophia vitreoretinalis hereditaria) – autosomal dominant; flat midface, cleft palate, myopia with retinal detachment, cataracts, hearing loss, arthropathy Clinics in Dermatol 24:521–533, 2006; J Med Genet 36:353, 359, 1999; Birth Defects 11:77–103, 1975 Tall people Transforming growth factor-beta receptor type II (TGFBR2) Nature Genet 36:855–860, 2004 Trisomy 13 mosaicism – severe aortic root dilatation, Marfanoid habitus Cytogenet Genome Res March 18, 2020 47, XYY syndrome Am J Dis Child 124:266–277, 1972 ZDHHC9 at Xq26 – mental retardation phenotype with Marfanoid habitus

MASSES OF THE HEAD AND NECK  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Lupus erythematosus, including tumid lupus JAAD 41:250–253, 1999; Am J Dermatopathol 21:356–360, 1999 Rheumatoid nodulosis Arthritis Rheum 40:175–178, 1997

CONGENITAL Accessory auricle Amnion rupture sequence Syndromes of the Head and Neck, 3rd Edition, pp. 11–13, 1990 Aneurysmal bone cyst

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Branchial cleft cyst – over the sternocleidomastoid muscle (second pharyngeal arch); rarest is the fourth branchial cleft cyst Proc (Baylor Univ Med Ctr) 29:183–184, 2016 Bronchogenic cyst Cephalocele – includes encephalocele, meningocele (rudimentary meningocele), meningoencephalocele, meningomyelocele; blue nodule with overlying hypertrichosis JAAD 46:934–941, 2002; AD 137:45–50, 2001 Cephalohematoma (cephalohematoma deformans) – blood between the outer table of the skull and periosteum; fixed Ped Clin North Amer 6:1151–1160, 1993 Congenital rhabdomyomatous mesenchymal hamartoma (striated muscle hamartoma) – skin-colored pedunculated (polypoid) nodule of the neck, midline of the chin, upper lip Ped Derm 16:65–67, 1999; Ped Derm 7:199–204, 1990; Ped Derm 3:153–157, 1986 Craniofacial deformations Syndromes of the Head and Neck, 3rd Edition, pp. 1–4, 1990 Dermoid cyst Ectopic thyroid tissue Esophageal diverticulum Holoprosencephalic disorders Syndromes of the Head and Neck, 3rd Edition, pp. 573–582, 1990 Hydrocephalus Syndromes of the Head and Neck, 3rd Edition, p. 592, 1990 Laryngocoele Lung herniation Meningocele Midline Arch Otolaryngol Head Neck Surg 113:418–420, 1987  Encephalocele   Nasal dermoid   Nasal glioma   Thyroglossal duct cyst Sialadenitis – in dehydrated neonates Teratoma Int J Ped Otorhinolaryngol 64:241–247, 2002 Thymic cyst Thyroglossal duct cyst and/or sinus – midline cervical mass Ped Clin North Amer 6:1151–1160, 1993; J Pediatr Surg 24:966–969, 1989; cleft with sinus tract JAAD 26:885–902, 1992; J Pediatr Surg 19:437–439, 1984 Thyroid gland – goiter; enlarged pyramidal lobe of the thyroid gland Ped Clin North Amer 6:1151, 1993

DEGENERATIVE DISEASES Facial nerve palsy

EXOGENOUS AGENTS

Cat scratch disease Arch Otolaryngol 95:277–281, 1972 Cervical lymphadenitis Chromomycosis – face and neck AD 113:1027–1032, 1997; BJD 96:454–458, 1977; AD 104:476–485, 1971 Cryptococcosis – supraclavicular mass Head and Neck 21:239– 246, 1999 Lymphadenopathy, reactive – supraclavicular mass Head and Neck 21:239–246, 1999 Mycobacterium tuberculosis – scrofuloderma (cervical scrofula) – infected lymph node, bone, joint, lacrimal gland with overlying red-blue nodule which breaks down, ulcerates, forms fistulae, scarring with adherent fibrous masses which may be fluctuant and draining BJD 134:350–352, 1996; Ped Clin North Amer 6:1151– 1160, 1993; Head Neck 11:60–66, 1989 Myiasis, furuncular – Dermatobia hominis – scalp cyst in a child Ped Derm 15:116–118, 1998; mimicking ruptured epidermoid cyst Can J Surg 33:145–146, 1990; house fly BJD 76:218–222, 1964; New World screw worm (Cochliomyia), Old World screw worm (Chrysomya), tumbu fly (Cordylobia) BJD 85:226–231, 1971; black blowflies (Phormia) J Med Entomol 23:578–579, 1986; green bottle (Lucilia), bluebottle (Calliphora), flesh flies (Sarcophaga, Wohlfahrtia) Neurosurgery 18:361–362, 1986; rodent botflies (Cuterebra) JAAD 21:763–772, 1989; human botflies (Dermatobia hominis) AD 121:1195–1196, 1985; AD 126:199–202, 1990 Nocardia Non-tuberculous mycobacteria Ped Inf 60:1062–1067, 2018; Ped Radiol 33:402–406, 2003; Orolaryngol Pol 57:17–23, 2003 North American blastomycosis – neck mass from extension of pulmonary disease South Med J 91:946–948, 1998 Onchocercoma Osteomyelitis Periapical abscess Pharyngeal abscess Pott’s puffy tumor – fluctuant nodule over frontal region in patients with chronic sinusitis JAAD 46:934–941, 2002 Pseudomycetoma of the scalp – multiple scalp nodules; Trichophyton schoenleinii BJD 145:151–153, 2001 Rhinosporidiosis – vascular nodules of the nose, extending to the pharynx or lips Mycopathologica 73:79–82, 1981 South American blastomycosis Tinea capitis (T. verrucosum, T. mentagrophytes) – kerion AD 114:371–372, 1978

INFILTRATIVE DISEASES Kikuchi’s disease Langerhans cell histiocytosis, including eosinophilic granuloma – congenital solid neck mass Ped Radiol 38:575–578, 2008

Paraffinomas – lumpy scalp AD 121:382–385, 1985

INFLAMMATORY DISEASES INFECTIONS AND INFESTATIONS Abscesses JAAD 46:934–941, 2002 AIDS – lymphoepithelioid cysts of the parotid glands in AIDS Head Neck 12:337–341, 1990 Actinomycosis Botryomycosis

Cervical adenitis Giant cell granuloma Lymphocytoma cutis Cancer 69:717–724, 1992; Acta DV (Stockh)62:119–124, 1982; Cancer 24:487–502, 1969 Sialadenitis – in neonate due to dehydration

Masses of the Head and Neck

METABOLIC DISEASES Alpha-1 anti-trypsin panniculitis

NEOPLASTIC DISORDERS Angiosarcoma Basal cell carcinoma

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144:1239–1243, 2001; AD 132:1376–1377, 1996; CTCL (fungating ulcerative mass) AD 124:409–413, 1988; Hodgkin’s disease – ulcerated papules, plaques, and nodules of the scalp and face AD 127:405–410 408, 1991; Hodgkin’s – large neck tumor Clin Nucl Med 40:602–605, 2015; spindle cell B-cell lymphoma BJD 145:313–317, 2001 Malignant eccrine spiradenoma of the scalp Derm Surg 25:45–48, 1999

Benign symmetric lipomatosis AD 125:238–239, 1990

Melanocytic nevus – giant cerebriform intradermal nevus Ann Plast Surg 19:84–88, 1987

Cancer of the oral cavity

Merkel cell tumor

Cheek tag

Metastases to the scalp JAAD 46:934–941, 2002; to cervical lymph nodes; supraclavicular masses; breast, uterine, cervical, lung, stomach, oropharyngeal carcinomas Head and Neck 21:239–246, 1999

Cylindroma; malignant cylindroma Dermatology 201:255–257, 2000 Cysts of the neck   Branchial cleft anomaly (cyst, sinus, and/or fistula) Bronchogenic cyst   Dermoid cyst

Mucocele of the lower lip

Epidermoid cyst   Eruptive vellus hair cysts   Heterotopic salivary gland tissue  Milia   Pilar cyst   Steatocystoma multiplex/simplex

Neuroblastoma

Thyroglossal duct cyst  Teratomas

Multiple myeloma Neurofibroma – lateral eyelid; mimics dermoid; plexiform Insights Imaging 9:571–589, 2018 Neurothekeoma – skin-colored scalp nodule BJD 144:1273–1274, 2001 Nuchal fibroma J Dermatol 34:262–263, 2007 Odontogenic cyst

Dermal dendrocytoma of the face AD 126:689–690, 1990

Osteoma

Dermatofibrosarcoma protuberans, myxoid Am J Surg Pathol 31:1371–1377, 2007

Paraganglioma – neck mass Ped Clin North Amer 6:1151–1160, 1993

Eccrine poroma Arch Craniofac Surg 18:44–45, 2017

Parotid mass

Epidermoid cyst, including epidermoid cysts of the cranial bones JAAD 46:934–941, 2002; Plast Reconstr Surg 97:1246–1248, 1996; Head Neck 14:415–418, 1992

Pilar cyst Plast Reconstr Surg 92:1207–1208, 1993 Pilomatrixoma Laryngorhinootologie 94:29–33, 2015

Eruptive fibromas J Cut Pathol 25(2):122–125, 1998

Pilomatrix carcinoma – multiple of the head and neck Otolaryngol Head Neck Surg 109:543–547, 1993; JAAD 23:985–988, 1990

Exostosis

Plasmacytoma Otolaryngol Head Neck Surg 119:614–618, 1998

Extraskeletal Ewing’s sarcoma Ped Derm 5:123–126, 1988

Post-auricular cyst

Fibrous dysplasia – side of the eyebrow; resembles dermoid Insights Imaging 9:571–579, 2018

Preauricular cyst

Ganglioneuroma of cervical sympathetic chain Ped Clin North Amer 6:1151–1160, 1993

Primary mucinous eccrine carcinoma – blue mass of the left cheek Am J Otolarygol 39:242–246, 2018

Granulocytic sarcoma Ear Nose Throat J 80:224–226, 2001

Proliferating trichilemmal tumor of the scalp J Dermatol 27:687–688, 2000; Ann Plast Surg 43:574–575, 1999; Mund Kiefer Gesechtschir 2:216–219, 1998; with malignant transformation Ann Plast Surg 41:314–316, 1998

Hibernoma – neck, axilla, central back; vascular dilatation overlying lesion AD 73:149–157, 1956 Infantile myofibromatosis – red scalp nodule AD 123:1391–1396, 1987

Preauricular tag

Ranula – retention cyst of the sublingual gland

Intracranial neoplasms with extension through the skull JAAD 46:934–941, 2002

Rhabdomyosarcoma – neck nodule in children JAAD 31:871–876, 1994; Ped Clin North Amer 6:1151–1160, 1993

Kaposi’s sarcoma Otolaryngol Head Neck Surg 111:618–624, 1994; Ann Int Med 103:744–750, 1985

Salivary gland tumors

Keloids

Schwannoma – supraclavicular mass Head and Neck 21:239–246, 1999

Keratoacanthoma Dermatology 200:317–319, 2000; Otolaryngol Head Neck Surg 93:112–116, 1985; Ann Plast Surg 3:172–176, 1979 Leukemia cutis JAAD 34:375–378, 1996 Lipoma JAAD 46:934–941, 2002 Lipomatous congenital melanocytic nevus – presenting as neck mass Head Neck Pathol 74:404–408, 2013 Lymphoma JAAD 46:934–941, 2002; follicular-center B-cell lymphoma – nodules of the face, scalp, trunk, extremities BJD

Sarcoma JAAD 46:934–941, 2002

Sebaceoma, giant J Dermatol 21:367–369, 1994 Sebaceous gland carcinoma AD 137:1367–1372, 2001; Nippon Ganka Gakkai Zasshi 104:740–745, 2000 Skin tags Korean J Audiol 16:10–13, 2012 Spiradenocarcinoma – vascular scalp nodule Cutis 69:455–458, 2002

638 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Squamous cell carcinoma Derm Surg 28:268–273, 2002; JAAD 23:1174–1175, 1990; JAAD 10:372–378, 1984 Thyroid adenoma, carcinoma, colloid cysts – neck nodules Ped Clin North Amer 6:1151–1160, 1993; thyroid carcinoma Head Neck 11:410–413, 1989 Trichoblastoma – scalp Am J Dermatopathol 15:497–502, 1993 Triton tumor – mature skeletal muscle and neural tissue Korean J Pathol 47:74–76, 2013 Warthin’s tumor, extraparotid – skin-colored neck nodule JAAD 40:468–470, 1999

SYNDROMES Adiposis dolorosa Brooke-Spiegler syndrome – trichoepitheliomas, cylindromas, and spiradenomas (turban tumors) of the face, scalp, and upper trunk Int J Dermatol 53:246–249, 2014; Dermatol Surg 26:877–882, 2000

Lowry syndrome – craniosynostosis with tower skull, ptosis of eyelids, strabismus Syndromes of the Head and Neck, 3rd Edition, p. 555, 1990 Lumpy scalp syndrome – autosomal dominant; irregular scalp nodules, deformed pinnae, rudimentary nipples Clin Exp Dermatol 15:240, 1989 Madelung’s deformity Maffucci’s syndrome Syndromes of the Head and Neck, 3rd Edition, p. 383, 1990 Meckel syndrome – dysencencephalia splanchnocystica Syndromes of the Head and Neck, 3rd Edition, pp. 724–727, 1990 Multiple endocrine neoplasia syndrome type II – medullary carcinoma of the thyroid Ped Clin North Amer 6:1151–1160, 1993 Neurofibromatosis Syndromes of the Head and Neck, 3rd Edition, p. 395, 1990 Nevoid basal cell carcinoma syndrome (Gorlin’s syndrome) – jaw cysts Syndromes of the Head and Neck, 3rd Edition, p. 373, 1990

Cloverleaf skull Syndromes of the Head and Neck, 3rd Edition, pp. 536–539, 1990

Oculo-auriculo-vertebral spectrum (Goldenhar syndrome) Syndromes of the Head and Neck, 3rd Edition, pp. 641–649, 1990

COH syndrome – cloverleaf skull, polymicrogyria, absent olfactory tracts and bulbs, proptosis, low nasal bridge, short upturned nose, downturned mouth, narrow palate, thumb duplication, small fifth fingers, micropenis, bifid scrotum, agenesis of cervical thymic lobes, bilobed lungs Syndromes of the Head and Neck, 3rd Edition, pp. 546–547, 1990

PHACES syndrome

Craniofacial dysostosis Syndromes of the Head and Neck, 3rd Edition, p. 549, 1990 Craniotelencephalic dysplasia Syndromes of the Head and Neck, 3rd Edition, p. 550, 1990 Encephalocutaneous cranial lipomatosis J Paediatr Child Health 36:603–605, 2000; Am J Med Genet 91:261–266, 2000; Ann DV 124:549–551, 1997 Epidermal nevus syndrome Syndromes of the Head and Neck, 3rd Edition, p. 364, 1990 Farber’s disease (disseminated lipogranulomatosis) – red papules and nodules of joints and tendons of the hands and feet; deforming arthritis; papules, plaques, and nodules of the ears, back of the scalp and trunk Am J Dis Child 84:449–500, 1952 Fibrodysplasia ossificans progressiva – fibrous scalp nodules Clev Clin Q 51:549–552, 1984 Frontonasal malformation (frontonasal dysplasia, median cleft face syndrome) Syndromes of the Head and Neck, 3rd Edition, pp. 785– 789, 1990

Proteus syndrome – port wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, and trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation Pediatrics 76:984–989, 1985; Am J Med Genet 27:87–97, 1987; Eur J Pediatr 140:5–12, 1986; Arch Fr Pediatr 47:441–444, 1990 (French) Steatocystoma multiplex

VASCULAR DISORDERS Aneurysmal dilatation of the internal jugular vein – soft blue neck mass; BMC Ear Nose Throat Disord June 14, 2009; Ped Clin North Amer 6:1151–1160, 1993 Angiosarcoma (Wilson-Jones angiosarcoma) – nodule or plaque JAAD 40:872–876, 1999; Int J Dermatol 38:697–699, 1999; JAAD 38:143–175, 1998; BJD 136:752–756, 1997; Cancer 59:1046–1057, 1987; multiple nodules BJD 144:380–383, 2001 Arteriovenous malformation JAAD 46:934–941, 2002 Behcet’s disease, vascular Tohoku J Exp Med 206:81–84, 2005

Gardner’s syndrome – nuchal-type fibroma; lipomas, epidermoid cysts Am J Surg Pathol 24:1563–1567, 2000; Syndromes of the Head and Neck, 3rd Edition, p. 367, 1990

Cystic hygroma (lymphatic malformation) Ped Clin North Amer 6:1151–1160, 1993; NEJM 309:822–825, 1983

Great hypertrophy of masseter

Hemangioma of the face and scalp – giant hemangiomas of the scalp S Afr Med J 55:47–49, 1979; of face; symptomatic hemangiomas of the airway with airway obstruction and cutaneous hemangiomas in a “beard” distribution J Pediatr 131:643–646, 1997

Infantile myofibromatosis – red to skin-colored nodules AD 134:625–630, 1998 Juvenile hyaline fibromatosis (systemic hyalinosis) – translucent papules or nodules of the scalp, face, neck, trunk, gingival hypertrophy, flexion contractures of large and small joints Ped Derm 18:400–402, 2001; JAAD 16:881–883, 1987 Kawasaki’s disease – cervical adenopathy Ped Clin North Amer 6:1151–1160, 1993 Lateral proboscis and cleft lip-palate Syndromes of the Head and Neck, 3rd Edition, pp. 775–776, 1990

Granulomatosis with polyangiitis

Lymphangioma Retiform hemangioendothelioma – exophytic masses of the scalp, arms, legs, and penis JAAD 38:143–175, 1998 Thrombus in temporal artery aneurysm Venous malformation – of scalp Insights Imaging 9:571–589, 2018; Zentralbl Neurochir 59:274–277, 1998

Melanoma, Clinical Simulators

MELANOMA, CLINICAL SIMULATORS MELANOCYTIC

PURPURIC LESIONS Infarcted acrochordon Chalazion

Acquired melanocytic nevus

Hemorrhage in the stratum corneum (talon noir)

Ancient melanocytic nevus Am J Dermatopathol 33:127–130, 2011

Nail bed or nail plate hemorrhage

Blue nevus

Ruptured epidermoid cyst

Congenital melanocytic nevus Dysplastic melanocytic nevus Halo nevus Melanocytic nevus and hemangioma – personal observation Melanocytic nevus in Hermansky-Pudlak syndrome Multiple melanomas – Li-Fraumeni syndrome AD 147:248–250, 2011

TATTOOS OR FOREIGN BODY DEPOSITION Acquired localized ochronosis Cosmetic tattoos Foreign body granuloma Mercury injections

Nevus spilus

Minocycline – periungual pigmentation

Pigmented spindle cell nevus Semin Diagn Pathol 15:225–229, 1998

Silver nitrate cautery

Recurrent pigmented melanocytic nevus Arch Pathol Lab Med 115:122–126, 1991

Suture granuloma

Sclerosing nevus with pseudomelanomatous features (nevus with regression-like fibrosis) Dermatology 219:202–208, 2009

Traumatic (graphite tattoo)

Silver particles Tattoos

Simple lentigo Spitz nevus

INFECTIONS AND INFESTATIONS

Targetoid hemosiderotic nevus Dermatology 210:200–205

Mycetoma

UV-irradiated melanocytic nevus Am J Dermatopathol 17:1–6, 1995

Plantar wart Tick

MELANOTIC LESIONS

Tinea nigra

Bowenoid papulosis Inverted follicular keratosis

ADNEXAL TUMORS

Keratoacanthoma

Apocrine hidrocystoma

Labial lentigo

Eccrine hidrocystoma

Lichen planus-like keratosis

Pigmented eccrine poroma Int J Dermatol 34:857–858, 1995

Melanosis of the vulva or penis

Pigmented eccrine porocarcinoma

Paget’s disease, extramammary Paget’s disease

Pigmented pilomatrixoma

Pigmented basal cell carcinoma

Plantar pseudochromhidrosis

Pigmented actinic keratosis (large cell acanthoma)

Trichilemmoma

Pigmented Bowen’s disease

Trichilemmal carcinoma

Solar lentigo Seborrheic keratosis AD 143:373–376, 2007 Squamous cell carcinoma

OTHER LESIONS Dermatofibroma

VASCULAR LESIONS

Dermatofibrosarcoma protuberans JAAD 25:355–374, 1996 Atypical fibroxanthoma

Angiokeratoma

Malignant fibrous histiocytoma

Blue rubber bleb nevus syndrome – mimics metastatic melanoma

Primary pigmented breast carcinoma

Hemangioma

Merkel cell tumor

Kaposi’s sarcoma

Leiomyosarcoma Clinics in Dermatology 20:212–221, 2002

Pyogenic granuloma

Melanoma syndromes JAAD 74:395–407, 2016

Sclerosing hemangioma (dermatofibroma)

BRCA1

Thrombosed capillary aneurysm

BRCA2

Venous lake

Cowden’s syndrome

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640 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Familial atypical mole syndrome Li-Fraumeni syndrome – p53 syndrome Melanoma-astrocytoma syndrome MITF syndrome POT1 syndrome TERT syndrome BAP1 tumor syndrome – pink papules; melanoma, uveal melanoma, internal malignancy Xeroderma pigmentosum

MELANONYCHIA SINGLE BAND NON-NEOPLASTIC Amodiaquine – transverse melanonychia J Drugs Dermatol 16:814–815, 2017 Bacterial subungual infections – Pseudomonas aeruginosa, Klebsiella spp., Proteus spp. – longitudinal melanonychia Dermatol Clin 33:185–195, 2015; Derm Surg 27:580–584, 2001 Bleomycin – transverse melanonychia J Drugs Dermatol 16:814– 815, 2017

Laugier-Hunziker syndrome – one or more digits JAAD 25:632–636, 1991 Lichen planus Dermatol Clin 33:185–195, 2015; BJD 113:369–374, 1985 Longitudinal melanonychia striata – black band Methotrexate – transverse melanonychia J Drugs Dermatol 16:814–815, 2017 Nail biting (onychophagia) Ped Derm 29:488–489, 2012; Dermatologica 181:126–128, 1990 Onychomycosis – Trichophyton rubrum JAAD 74:1121–1127, 2016; JAAD 65:1219–1227, 2011; Dermatol Clin 33:185–195, 2015; JAAD 56:835–847, 2007; JAAD 31:311–316, 1994; Scytalidium dimidiatum JAAD 66:830–841, 2012; JAAD 56:835–847, 2007; Dermatology 202:183–185, 2001 Onychopapilloma – V-shaped distal split of the nail, longitudinal erythronychia, longitudinal leukonychia, onycholysis, longitudinal melanonychia, splinter hemorrhages, distal subungual hyperkeratotic mass JAAD 74:521–526, 2016 Phaeohyphomycosis of the nail – Wangiella dermatitidis Clin Exp Derm 17:83–86, 1992 Post-inflammatory hyperpigmentation Post-traumatic – pseudo-Hutchinson’s sign G Ital Dermatol Venereol 152:96–97, 2017 Potassium permanganate Dermatol Clin 33:185–195, 2015

Blood – longitudinal melanonychia Derm Surg 27:580–584, 2001

Racial JAAD 59:785–791, 2008

Carpal tunnel syndrome JAAD 2020 March 18; SO190–9622(20)30436–9

PUVA – transverse melanonychia J Drugs Dermatol 16:814–815, 2017

Chloroquine – transverse melanonychia J Drugs Dermatol 16:814–815, 2017

Quinacrine – transverse melanonychia J Drugs Dermatol 16:814– 815, 2017

Congenital longitudinal melanonychia Acta DV Alp Pannonica Adriat 26:119–120, 2017

Racial JAAD 74:1121–1127, 2016

Cyclophosphamide – transverse melanonychia J Drugs Dermatol 16:814–815, 2017

Silver nitrate JAAD 56:835–847, 2007

Dacarbazine – transverse melanonychia J Drugs Dermatol 16:814–815, 2017 Daunorubicin – transverse melanonychia J Drugs Dermatol 16:814–815, 2017 Doxorubicin – transverse melanonychia J Drugs Dermatol 16:814– 815, 2017 Electron beam therapy – transverse melanonychia J Drugs Dermatol 16:814–815, 2017; JAAD 53:S112–114, 2005 Emtricitabine Green slime (exogenous) JAMADerm 156:102, 2020 Hair dye JAAD 56:835–847, 2007 Hematoma JAAD 56:835–847, 2007 Henna JAAD 56:835–847, 2007 Hydroxyurea JAAD 49:339–341, 2003; transverse melanonychia J Drugs Dermatol 16:814–815, 2017; Int J Derm 45:1329–1339, 2006; Clin Exp Dermatol 27:8–13, 2002; JAAD 47:146–147, 2002 5-Fluorouracil, topical BJD 112:621–625, 1985; transverse melanonychia J Drugs Dermatol 16:814–815, 2017 Foreign body (subungual) Friction Dermatologica 174:280–284, 1987 Fungus JAAD 66:830–841, 2012 Infliximab transverse melanonychia J Drugs Dermatol 16:814–815, 2017

Radiotherapy AD 139:1209–1214, 2003 Staining JAAD 74:1121–1127, 2016 Subungual hemorrhage Dermatol Clin 33:185–195, 2015; Ped Derm 21:462–465, 2004; hematoma – longitudinal melanonychia Derm Surg 27:580–584, 2001 Tinea nigra JAAD 54:664–667, 2006 Trauma, acute, or chronic JAAD 74:1121–1127, 2016; Dermatol Clin 33:185–195, 2015; AD 139:1209–1214, 2003; after tangential pigmented nail matrix excision JAAD 69:96–104, 2013 Verruca vulgaris Semin Cutan Med Surg 28:49–54, 2009 Zidovudine JAAD 63:549–561, 2010; transverse melanonychia J Drugs Dermatol 16:814–815, 2017 NEOPLASTIC Atypical melanocytic hyperplasia – longitudinal melanonychia JAAD 72:773–779, 2015; Derm Surg 27:580–584, 2001; lentiginous melanocytic proliferation JAAD 79:327–336, 2018 Benign melanocytic hyperplasia JAAD 59:785–791, 2008 Basal cell carcinoma JAAD 16:229–233, 1987 Blue nevus – common blue nevus of nail matrix AD 139:1209–1214, 2003 Bowen’s disease Dermatol Clin 33:185–195, 2015; Eur J Dermatol 25:617–618, 2015; BJD 158:1273–1279, 2008; Derm Surg 32:1522–1525, 2006; Cutis 72:305–309, 2003; JAAD 39: 490–493, 1998; JAAD 18:1359–1360, 1988; J Hand Surg (Am)3:184–186,

Melanonychia 1978; HPV-type 56-associated Bowen’s disease – longitudinal melanonychia; pigmented hyperkeratotic plaque BJD 167:1161– 1164, 2012; HPV67 Acta DV 95:745–746, 2015 Fibrous histiocytoma, subungual Keratosis, subungual of the nail bed BJD 140:730–733, 1999 Lentigo simplex – longitudinal melanonychia JAAD 72:773–779, 2015; Derm Surg 27:580–584, 2001 Melanocytic hyperplasia, benign – longitudinal melanonychia Derm Surg 27:580–584, 2001 Melanocytic nevus – longitudinal melanonychia JAAD 75:535–540, 2016; JAAD 74:1121–1127, 2016; Dermatol Clin 33:185–195, 2015; JAAD 72:773–779, 2015; JAAD 56:835–847, 2007; JAAD 54:664– 667, 2006; Derm Surg 27:580–584, 2001; nail matrix nevi JAAD 34:765–771, 1996; junctional nevus Ped Derm 21:462–465, 2004; multiple congenital melanocytic nevi JAAD 27:853–854, 1992; spotted grouped pigmented nevi Act D V 56:345–351, 1976; deep penetrating nevus AD 139:1608–1610, 2003; recurrent nevus phenomenon Melanoma JAAD 80:1272–1273, 2019; JAAD 74:1121–1127, 2016; Dermatol Clin 33:185–195, 2015; JAMA 311:1350–1351, 2014; Ped Derm 29:79–83, 2012; BJD 165:852–858, 2011; AD 146:382–387, 2010; JAAD 56:835–847, 2007; JAAD 54:664–667, 2006; Derm Surg 27:294–295, 2001; BJD 143:431–434, 2000; Ann Surg 161:545–552, 1987; Cancer 46:2492–2504, 1980; melanoma in situ AD 140:1102–1106, 2004; longitudinal gray-pigmented band with distal splitting JAMADerm 150:199–200, 2014

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DRUGS Amlodipine BJD 153:219–220, 2005 Antimalarials – amodiaquine, quinacrine, chloroquine JAAD 53:S112–114, 2005 Azathioprine J Clin Rheumatol April 3, 2019 Bleomycin JAAD 21:1165–1175, 1989 Busulfan JAAD 21:1165–1175, 1989 Cyclophosphamide Kidney Int 90:13–87, 2016; JAAD 71:203–214, 2014; JAAD 21:1165–1175, 1989 Dacarbazine JAAD 53:S112–114, 2005 Daunorubicin Diquat Docetaxel Cutan Ocul Toxicol 29:296–299, 2010 Doxorubicin JAMA 228:460, 1974 Doxycycline Ann Pharmacother 49:1175–1176, 2015 5-Fluorouracil JAAD 71:203–214, 2014; JAAD 21:1165–1175, 1989 Fluconazole Int J Derm 37:719–720, 1998 Gold therapy Ped Derm 21:462–465, 2004 Hydroxycarbamide JAAD 2020 Apr 11:50190–9622(20)30564–8; Case Rep Hematol 2015:653178.doi.10.1155/2015/653178; Rheumatol Clinics 9:2-381–382, 2013 Hydroxychloroquine in SLE Rheumatol Clin 9:381–382, 2013

Melanoma is situ Ann Dermatol 29:653–654, 2017; total melanonychia Dermatol Surg 40:1154–1157, 2014; J Dermatol 35:754– 758, 2008

Hydroxyurea BMJ Case Rep Feb 15, 2017; JAAD 49:339–341, 2003; Int J Derm 39:928–931, 2000; transverse melanonychia J Drugs Dermatol 16:814–815, 2017

Melanotic macule JAAD 54:664–667, 2006 Metastatic breast carcinoma

Imatinib – transverse melanonychia Indian J Dermatol 60:412–413, 2015; Clin Exp Dermatol 37:432–433 2012

Metastatic melanoma

Infliximab – transverse melanonychia J Eur Acad DV 16:250, 2002

Myxoid cyst

Interferon-alpha – treatment for chronic hepatitis C; melanonychia, facial hyperpigmentation, hyperpigmentation of the tongue and buccal mucosa JAMA Derm 149:675–677, 2013

Onychocytic carcinoma Am J Dermatopathol 35:679–684, 2013 Onychomatricoma JAMADerm 154:1473–1474, 2018; Dermatol Clin 33:185–195, 2015; JAMADerm 150:449–450, 2014; JAMADerm 150:335–337, 2014

Ketoconazole Melphalan Arch Derm Res 258:81–83, 1977

Onychopapilloma Dermatol Clin 33:185–195, 2015

Mepacrine

Proliferation of normal melanocytes

Methotrexate JAAD 21:1165–1175, 1989

Postoperative recurrent/persistent melanocytosis

Minocycline

Squamous cell carcinoma (pigmented) of the nail apparatus Cutis 101:375–377, 2018; Eur J Dermatol 27:561–563, 2017; BJD 169:198–199, 2013; JAAD 69:253–261, 2013; JAAD 58:323–326, 2008; BJD 156:871–874, 2007

Nitrogen mustard

Subungual acanthoma J Eur Acad DV 32:1608–1613, 2018 Subungual keratosis J Dermatol 39:930–931, 2012

Nitrosourea JAAD 21:1165–1175, 1989 Paclitaxel Cutis 95:e12–14, 2015 Phenothiazine Phenytoin Plaquenil

MULTIPLE BANDS

Psoralen (PUVA) Clin Exp Dermatol 40:331–332, 2015; JAAD 48:S31–32, 2003; Photodermatol 6:98–99, 1989

NON-NEOPLASTIC

Sulfonamide

AUTOIMMUNE DISEASES AND DISORDERS OF IMMUNE DYSREGULATION Graft vs. host disease Lupus erythematosus – diffuse melanonychia Ann DV 147:18–28, 2020; JAAD 56:835–847, 2007; JAAD 47:S187–188, 2002 Scleroderma Jnl Clin Rheumatol 20:118–119, 2014; JAAD 56:835–847, 2007; JAAD 50:E5, 2004

Tetracycline Timolol Voriconazole Clin Exp Dermatol 43:75–76, 2018 Zidovudine BJD 126:387–391, 1992 EXOGENOUS AGENTS Phenolphthalein

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

INFECTIONS AND INFESTATIONS

PRIMARY CUTANEOUS DISORDERS

HIV/AIDS – longitudinal or transverse melanonychia AD 134:1216– 1220, 1998; Int J Derm 16:615–630, 1987

Acanthosis nigricans

Acrotherium nigrum Alternaria grisea tenius

Lichen planus JAAD 56:835–847, 2007; Cutis 67:409, 411, 2001; Acta DV 70:338–339, 1990; Acta DV 69:338–339, 1989; BJD 113:369–370, 1985

Bacterial subungual infections – Pseudomonas aeruginosa, Klebsiella spp., Proteus spp. – longitudinal melanonychia Derm Surg 27:580–584, 2001

Lichen striatus Am J Clin Dermatol 12:101–102, 2011

Bacteria coexisting with onychomycosis

Pustular psoriasis JAAD 56:835–847, 2007

Blastomycetes

Racial variation – longitudinal brown streaks of nails; AfricanAmerican, Hispanic, Indian, Japanese JAAD 56:835–847, 2007; AD 105:548–550, 1972; AD 25:876–881, 1932

Candida – C. parapsilosis J Dermatol 46:911–913, 2019; C. albicans Int J Dermatol 52:1598–1600, 2013 Exophiala Mycoses 56:187–188, 2013 Fusarium oxysporum Mycoses 55:e40–41, 2012 Hendersonula toruloidea Hormodendrum elatum Onychomycosis – Trichophyton rubrum Cutis 94:E5–6, 2014 Pinta Proteus mirabilis

Premature canities Genetic Skin Disorders, 2nd Edition, 2010, pp. 367–369

PSYCHOCUTANEOUS DISEASES Nail biting and/or picking JAAD 56:835–847, 2007; Dermatologica 181:126–128, 1990; NEJM 282:345, 1970 Onychophagia Case Rep Dermatol Med Jan 30, 2018; Ped Derm 29:488–489, 2012 Onychotillomania – total melanonychia; nail dystrophy Am J Clin Dermatol 18:763–770, 2017; JAAD 75:1245–1250, 2016

Syphilis, secondary Trichophyton soudanense

SYNDROMES

Wangiella Clin Exp Dermatol 17:83–86, 1992

Carney complex – personal observation

METABOLIC DISORDERS Acromegaly JAAD 56:835–847, 2007 Addison’s disease JAAD 58:522–524, 2008; Ped Derm 21:462–465, 2004; G Ital DV 123:539–540, 1988; JAAD 21:1165–1175, 1989; JAMA 215:1666–1667, 1971; Br Med J 1:1582–1583, 1966 Adrenalectomy for Cushing’s disease JAAD 56:835–847, 2007; JAMA 215:1666–16667, 1971; NEJM 281:1056–1057, 1969 Alkaptonuria Int J Dermatol 58:1239–1245, 2019 Cushing’s syndrome Folic acid deficiency JAAD 56:835–847, 2007; AD 122:896—899, 1986; BJD 97:105–106, 1977 Hemochromatosis Ped Derm 21:462–465, 2004 Hyperbilirubinemia Hyperthyroidism JAAD 56:835–847, 2007; Derm Clin 3:431–443, 1985 Malnutrition Lancet 10:507–508, 1962 Pernicious anemia Ped Derm 21:462–465, 2004 Pituitary adenoma Clin Exp Dermatol 38:689–690, 2013 Porphyria Int J Dermatol 58:1239–1245, 2019 Pregnancy JAAD 56:835–847, 2007; AD 139:1209–1214, 2003 Vitamin B12 deficiency JAAD Case Reports 6:372–373, 2020; JAAD 56:835–847, 2007; AD 122:896—899, 1986; BJD 97:105– 106, 1977

NEOPLASTIC Breast carcinoma Arch Int Med 138:1302–1303, 1978 Melanoma – both thumbs JAAD 58:S42–44, 2008; melanoma in situ J Drugs Dermatol 16:268–270, 2017 Squamous cell carcinoma, pigmented BJD 169:198–199, 2013

Laugier-Hunziker syndrome Endocrinol Diabetes Metab Case Rep July 26, 2018; AD 143:631–633, 2007; J Eur Acad Dermatol Venereol 15:574–577, 2001; Hautarzt 42:512–515, 1991; JAAD 25:632–636, 1991; Clin Exp Derm 15:111–114, 1990; AD 115:1448–1449, 1979 Peutz-Jeghers syndrome Int J Dermatol 58:1239–1245, 2019; Am J Gastroenterol 43:56–58, 1965 TOXINS Arsenic poisoning AD 139:1209–1214, 2003 Mercury TRAUMA Electron beam therapy – transverse melanonychia JAAD 53:S112– 114, 2005 Frictional longitudinal melanonychia Dermatologica 174:280–284, 1987 Hematoma JAMADerm 154:1473–1474, 2018 Irradiation (systemic) Radiation dermatitis JAAD 56:835–847, 2007 Traumatic X-ray therapy – transverse melanonychia Radiother Oncol 114:282– 283, 2015; AD 90:174–176, 1964; JAMA 150:210–211, 1952

MICROCEPHALY SYNDROMES AEC syndrome (Hay-Wells syndrome) – ankyloblepharon, ectodermal dysplasia, cleft lip/palate syndrome – blepharitis, eyelid papillomas, periorbital wrinkling; microcephaly, widespread congenital scalp erosions; alopecic ulcerated plaques of the scalp, trunk, groin; alopecia of the scalp and eyebrows; congenital

Microcephaly

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erythroderma; depigmented patches; syndactyly; bony abnormalities; widely spaced nipples; TP63 mutation Ped Derm 26:617–618, 2009; AD 141:1591–1594, 2005; AD 141:1567–1573, 2005; AD 134:1121–1124, 1998; Ped Derm 14:149–150, 1997; generalized fissured erosions of the trunk BJD 149:395–399, 2003; TP63 mutations seen in AEC syndrome, EEC syndrome, RappHodgkin syndrome, limb-mammary syndrome, split-hand split-foot malformation type 4, acro-dermato-ungual-lacrimal-tooth syndrome AD 141:1567–1573, 2005

anomalies (kyphoscoliosis), joint contractures; overhanging upper lip, small jaw JAAD 75:873–882, 2016; Ped Derm 26:97–99, 2009; JAMA Derm 149:1414–1418, 2013

Aicardi-Goutieres syndrome (interferonopathy) – autosomal recessive; neurodegenerative disease; mutation in three-prime repair exonuclease 1 (TREX1;AGS1); mutation in sterile alpha motif domain and HD domain-containing protein1 (SAMHD1;AGS5); myutation in three genes encoding for components of ribonuclease H subunit A endonuclease complex (AGS2–4); mutation in gene for RNA-specific adenosine deaminase 1 (AGS6); mutation in gene for interferon-induced helicase-C domain-containing protein 1 (AGS7); chilblain-like lesions; acrocyanosis; red periungual lesions; red earlobes; livedo reticularis, blueberry muffin baby; congenital encephalopathy with developmental delay; microcephaly; narrow facial features; seizures, spasticity, dystonic posturing Ped Derm 33:602–614, 2016

Cleft palate, microcephaly, large ears, and short stature (Say syndrome) Am J Med Genet 45:358–360, 1993; Syndromes of the Head and Neck, 3rd Edition, p. 756

Christian syndrome Syndromes of the Head and Neck, 3rd Edition, p. 544 Chromosomal aberrations Cleft lip-palate, microcephaly, mental retardation, and holoprosencephaly, Syndromes of the Head and Neck, 3rd Edition, p. 749–750

Cockayne syndrome – xerosis with rough, dry skin, anhidrosis, erythema of the hands, hypogonadism; autosomal recessive; short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature-aged appearance with loss of subcutaneous fat and sunken eyes, canities, mental deficiency, photosensitivity, cyanotic livedo reticularis, disproportionately large hands, feet, and ears, dental caries, sensorineural hearing loss, ocular defects including retinal degeneration, demyelination JAAD 75:873–882, 2016; JAMA Derm 149:1414–1418, 2013; Ped Derm 20:538–540, 2003; Am J Hum Genet 50:677–689, 1992; J Med Genet 18:288–293, 1981; bird-headed dwarfism Rook, p. 3261, 1998, 6th Edition

Albright’s hereditary osteodystrophy – pseudohypoparathyroidism, round face, short neck, osteomas of the skin with overlying hyperpigmentation, short stature, hypogonadism, macrocephaly, psychomotor retardation, endocrinologic abnormalities; mutation in GNAS1 Ped Derm 28:135–137, 2011; Endocrinology 30:922–932, 1942

Coffin-Siris syndrome Syndromes of the Head and Neck, 3rd Edition, p. 831

Angelman syndrome – deletion of 15q11.2–q13; UBE3A mutations NEJM 371:847–858, 2014; Syndromes of the Head and Neck, 3rd Edition, p. 616

Congenital muscular dystrophies – cobblestone dysplasia of the brain NEJM 371:847–858, 2014

Aniridia-Wilms’ tumor syndrome Syndromes of the Head and Neck, 3rd Edition, p. 51 Anonychia and microcephaly Am J Med Genet 66:257–260, 1996 Autosomal recessive primary microcephaly (microcephaly vera) – mutations in ASPM and WDR62 NEJM 371:847–858, 2014 Bloom’s syndrome Syndromes of the Head and Neck, 3rd Edition, p. 297 Borjeson-Forssman-Lehmann syndrome Syndromes of the Head and Neck, 3rd Edition, p. 351 Braegger syndrome – proportionate short stature, IUGR, ischiadic hypoplasia, renal dysfunction, craniofacial anomalies, postaxial polydactyly, hypospadias, microcephaly, mental retardation Am J Med Genet 66:378–398, 1996 CDG-Ie – eyelid telangiectasia, hemangiomas, inverted nipples, microcephaly; neurologic abnormalities; dolichol-phosphatemannose synthase Ped Derm 22:457–460, 2005

COFS syndrome Syndromes of the Head and Neck, 3rd Edition, p. 623

Cornelia de Lange syndrome – mutations in NIPBL and SMC1A NEJM 371:847–858, 2014; Syndromes of the Head and Neck, 3rd Edition, p. 301, 304 Craniosynostosis Cri-du-chat syndrome Syndromes of the Head and Neck, 3rd Edition, p. 48 Del(1q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 69 Del(3p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 72 Del(4p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 46 Del(4q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 74 Del(5p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 48 Del(6q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 77 Del(7q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 79 Del(8p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 80 Del(11q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 85

CEDNIK syndrome (cerebral dysgenesis-neuropathy-ichthyosis-­ keratoderma) – microcephaly; dysmorphic face with small anterior fontanelles; pointed prominent nasal tip, small chin, inverted nipples and long toes, high palate, thick gingivae, cradle cap, sparse brittle coarse hair, scarring alopecia, fixed flexion posture; long eyelashes, enamel hypoplasia; decreased SNAP 29 protein; mutation in SNARE proteins mediating vesicle trafficking; mutation in ABCA12 gene Ped Derm 36:372–376, 2019; BJD 164:610–616, 2011; AD 144:334–340, 2008; Am J Hum Genet 77:242–251, 2005

Del(13q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 51

Cerebro-oculo-facial-skeletal syndrome (in aboriginal families) – microcephaly, facies – micrognathia, small eyes, enlarged ears, bulbous nose, prominent nasal bridge, microphthalmia with poor vision, cataracts, blepharophimosis, short palpebral fissures, onychogryphosis, photosensitivity, mental retardation, hyperkinesis, failure to thrive, developmental delay, hypotonia, orthopedic

Distal aphalangia, syndactyly, extra metatarsal, short stature, microcephaly, borderline intelligence – autosomal dominant Am J Med Genet 55:213–216, 1995

Del(14q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 88 Del(15q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 89 Del(16q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 91 Del(18p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 52 Del(18q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 53 DeSanctis-Cacchione syndrome – dwarfism, gonadal hypoplasia, mental deficiency, microcephaly, xeroderma pigmentosum

Dubowitz syndrome – autosomal recessive, microcephaly, sloping forehead, telecanthus, erythema, and scaling of the face and extremities in infancy, ichthyosiform eruption, sparse blond scalp

644 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 and arched eyebrow hair, dysplastic low-set ear pinnae, highpitched hoarse voice, delayed eruption of the teeth, growth retardation, craniofacial abnormalities; syndactyly, cryptorchidism, hypospadias, developmental delay, transitory short stature, hyperactive behavior, blepharophimosis, ptosis of the eyelids, epicanthic folds, broad nose, palate anomalies, micrognathia, and severe atopic dermatitis Ped Derm 22:480–481, 2005; Am J Med Genet 63:277–289, 1996; Clin Exp Dermatol 19:425–427, 1994; Am J Med Genet 47:959–964, 1993; Eur J Pediatr 144:574–578, 1986; Am J Med Genet 4:345–347, 1979; J Med Genet 2:12–17, 1965

hyperpigmentation (resembles dyskeratosis congenita), alopecia, growth retardation, microcephaly, mental retardation, cerebellar malformation, progressive bone marrow failure, and mucocutaneous lesions SKINmed 12:117–118, 2014; J Pediatr 136:390–393, 2000 Hunter syndrome Syndromes of the Head and Neck, 3rd Edition, p. 552 Hurst syndrome Syndromes of the Head and Neck, 3rd Edition, p. 553

Dup(4p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 73

Intrauterine exposure to teratogenic agents NEJM 371:847–858, 2014  Alcohol   Ionizing radiation   Medications and recreational drugs

Dup(4q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 75

Hypoxic-ischemic injury NEJM 371:847–858, 2014

Dup(5q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 77s

Inborn errors of metabolism

Dup(6q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 78

Ives-Houston syndrome Syndromes of the Head and Neck, 3rd Edition, p. 554

Dup(2p) syndrome Syndromes of the Head and Neck, 3 Edition, p. 70 rd

Dup(2q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 71

Dup(9q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 82 Dup(10q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 85 Dup(11q) syndrome Syndromes of the Head and Neck, 3 Edition, p. 86 rd

Dup(15q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 90 Dup(17p) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 72 Dup(17q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 92 Dup(19q) syndrome Syndromes of the Head and Neck, 3rd Edition, p. 92 Early infantile epileptic encephalopathy 10 (microcephaly, seizures, and developmental delay) – mutations in PNKP NEJM 371:847– 858, 2014 Ectrodactyly-ectodermal dysplasia-clefting syndrome Syndromes of the Head and Neck, 3rd Edition, p. 717 Emanuel syndrome – microcephaly, preauricular tag of sinus, ear anomalies, cleft or high-arched palate, micrognathia, congenital heart disease, structural brain abnormalities, genital anomalies in males Genet Counsel 23:319–328, 2012 Fanconi’s syndrome (pancytopenia with congenital defects) – generalized olive-brown hyperpigmentation, especially of the lower trunk, flexures, and neck with depigmented macules; hypoplastic anemia, slender build, short broad thumbs, tapered fingers, microcephaly, hypogonadism Semin Hematol 4:233–240, 1967 Fetal alcohol syndrome Syndromes of the Head and Neck, 3rd Edition, p. 16 Fetal brain disruption sequence Syndromes of the Head and Neck, 3rd Edition, p. 14 Fetal folate antagonists syndrome Syndromes of the Head and Neck, 3rd Edition, p. 21

Johanson-Blizzard syndrome – autosomal recessive; growth retardation, microcephaly, ACC of the scalp, sparse hair, hypoplastic ala nasi, CALMs, hypoplastic nipples and areolae, hypothyroidism, sensorineural deafness Clin Genet 14:247–250, 1978; Syndromes of the Head and Neck, 3rd Edition, p. 812 Kaufman syndrome Syndromes of the Head and Neck, 3rd Edition, p. 907 Langer-Gideon syndrome Syndromes of the Head and Neck, 3rd Edition, p. 808 Lenz-microphthalmia syndrome Syndromes of the Head and Neck, 3rd Edition, p. 815 Localized lipomatous hypertrophy with microcephaly, mental retardation, and deletion of short arm of chromosome 11 AD 116:622, 1980; AD 115:978–979, 1979 Lissencephaly or microlissencephaly; LIS1, DCX, ARX, NDE1 mutations NEJM 371:847–858, 2014 Malnutrition, severe Marden-Walker syndrome Syndromes of the Head and Neck, 3rd Edition, pp. 633–634. Marinesco-Sjogren syndrome – cataracts, mental retardation, microcephaly, short stature, hypogonadism, ataxia, hypotonia Clin Dysmorphol 4:283–288, 1995 Martsolf syndrome – cataracts, facial dysmorphism, microcephaly, short stature, hypogonadism Am J Med Genet 1:291–299, 1978; Syndromes of the Head and Neck, p. 906, 1990 Maxillofacial dysostosis – X-linked Syndromes of the Head and Neck, 3rd Edition, p. 655

Filippi syndrome – polydactyly, syndactyly, microcephaly, growth retardation, and mental retardation Am J Med Genet 87:128–133, 1999

Meckel syndrome – microcephaly, microphthalmia, congenital heart defects, postaxial polydactyly, polycystic kidneys, cleft lip/palate J Med Genet 8:285–290, 1971; Syndromes of the Head and Neck, 3rd Edition, p. 724

Focal dermal hypoplasia Syndromes of the Head and Neck, 3rd Edition, p. 472

Metabolic and systemic disease – severe hypoglycemia and renal failure NEJM 371:847–858, 2014

Goldenhar syndrome (oculo-auriculo-vertebral syndrome) Syndromes of the Head and Neck, 3rd Edition, p. 645

Methylenetetrahydrofolate reductase deficiency – microcephaly and episodic cyanosis NEJM 371:847–858, 2014

Head trauma and intracranial hemorrhage NEJM 371:847–858, 2014

Michelin tire baby syndrome – either nevus lipomatosis or diffuse smooth muscle hamartoma; degenerative collagen, scarring; excessive folds of firm skin on extremities, especially ankles and wrists; generalized hypertrichosis, palmar cerebriform plaques; low-set malformed ears with thickened helix and anti-helix; wide or depressed nasal bridge; epicanthic folds, hypertelorism, cleft palate, micro-ophthalmia or deep-set eyes, flate or hypoplastic midface, short neck, decreased hearing, hypoplastic malformed genitalia, micrognathia, histologically increased periadnexal fat and

Herrmann syndrome Syndromes of the Head and Neck, 3rd Edition, p. 550 Holoprosencephaly and microcephaly NEJM 371:847–858, 2014; Syndromes of the Head and Neck, 3rd Edition, p. 575 Hoyeraal-Hreidarsson syndrome – reticulate

Microcephaly subcutaneous fat and smooth muscle hamartomas; mental retardation, tendinous hyperlaxity, seizures, mastocytosis, complex malformation syndrome (bilateral calcaneovalgus deformity, cleft palate, inguinal hernia, hip deformity, clefting of lateral mouth commissures, shawl scrotum, absent foreskin; developmental delay, microcephaly, mental retardation Ped Derm 31:659–663, 2014; JAAD 63:1110–1111, 2010; Ped Derm 27:79–81, 2010; Ped Derm 24:628–231, 2007; Ped Derm 22:245–249, 2005; Ped Derm 20:150–152, 2003; BJD 129:60–68,1993; JAAD 28:364–370, 1993; Ped Derm 6:329–331, 1989; Am J Med Genet 28:225–226, 1987; AD 115:978–979, 1979; diffuse lipomatous hypertrophy AD 100:320–323, 1969; generalized muscular nevus Ann DV 107:923– 927, 1980 Microcephalic osteodysplastic primordial dwarfism type II – autosomal recessive; craniofacial dysmorphism with slanting palpebral fissures, prominent nose, small mouth, micrognathia; fine sparse hair and thin eyebrows; café au lait macules; xerosis; mottling; dark pigmentation of the neck and trunk; depigmentation (nevus depigmentosus); small pointed widely spaced teeth; low-set ears missing lobule; widened metaphyses and relative shortening of distal limbs; cerebrovascular anomalies Ped Derm 25:401–402, 2008 Microcephaly and cleft palate Syndromes of the Head and Neck, 3 Edition, p. 767

rd

Microcephaly and oligodontia Syndromes of the Head and Neck, 3rd Edition, pp. 871–872 Miller-Dieker syndrome Syndromes of the Head and Neck, 3rd Edition, p. 590 Mukamel syndrome – autosomal recessive; premature graying in infancy, lentigines, depigmented macules, mental retardation, spastic paraparesis, microcephaly, scoliosis Mulvihill-Smith progeria-like syndrome (premature aging syndrome) – multiple congenital melanocytic nevi, freckles, blue nevi, short stature, unusual birdlike facies, lack of facial subcutaneous tissue, xerosis, telangiectasias, thin skin, fine silky hair, premature aging, low birth weight, hypodontia, high-pitched voice, mental retardation, sensorineural hearing loss, hepatomegaly, microcephaly, immunodeficiency with chronic infections, progeroid, conjunctivitis, delayed puberty Am J Med Genet 69:56–64, 1997; J Med Genet 31:707–711, 1994; Am J Med Genet 45:597–600, 1993 Neu-Laxova syndrome – short neck; mild scaling to harlequin ichthyosis appearance; ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema and mildly edematous feet and hands, absent nails; microcephaly, intrauterine growth retardation, limb contractures, low-set ears, sloping forehead; small genitalia, eyelid and lip closures, syndactyly, cleft lip and palate, micrognathia; autosomal recessive; uniformly fatal Ped Derm 20:25–27,78–80, 2003; Curr Prob Derm 14:71–116, 2002; Clin Dysmorphol 6:323–328, 1997; Am J Med Genet 35:55–59, 1990 Neurodegenerative disorders Neuronal heterotopia Nijmegen breakage syndrome – autosomal recessive; chromosome instability syndrome; mutations in NBS-1 gene which encodes bibirin (DNA damage repair); microcephaly, receding mandible, prominent midface, prenatal-onset short stature, growth retardation, bird-like facies with epicanthic folds, large ears, sparse hair, clinodactyly/syndactyly; freckling of the face, café au lait macules, vitiligo, photosensitivity of the eyelids, telangiectasias; pigmented deposits of fundus; IgG, IgA deficiencies, agammaglobulinemia, decreased CD3 and CD4 T cells with recurrent respiratory and urinary tract infections Ped Derm 26:106–108, 2009; DNA Repair

645

3:1207–1217, 2004; Arch Dis Child 82:400–406, 2000; Am J Med Genet 66:378–398, 1996 Oculo-palato-cerebral dwarfism Syndromes of the Head and Neck, 3rd Edition, pp. 767–768 Patau’s syndrome (non-mosaic trisomy 13) – parieto-occipital scalp defects, cleft lip/palate, abnormal helices, low-set ears, loose skin of posterior neck, simian crease of the hand, hyperconvex narrow nails, polydactyly, microcephaly, microphthalmia, severe central nervous system anomalies, congenital heart defects, holoprosencephaly; death in first year Am J Med Genet 143A:1739– 1748, 2007; Ped Derm 22:270–275, 2005 PEHO – progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy syndrome NEJM 371:847–858, 2014 Polymicrogyria associated with microcephaly – TUBB2B mutation NEJM 371:847–858, 2014 Pontocerebellar hypoplasia – abnormal hindbrain; mutations in TSEN54, CASK, CHMP1A NEJM 371:847–858, 2014 Premature aging and multiple nevi Syndromes of the Head and Neck, 3rd Edition, p. 487 Prenatal, perinatal, and early postnatal infections of the central nervous system NEJM 371:847–858, 2014 PYCR1-related cutis laxa – hair loss, prominent scalp veins, triangular-­shaped face, microcephaly, short stature, hypermobility of joints, thin atrophic skin, wrinkled skin, muscle weakness, finger contractures Dtsch Arztebl Intl 16:489–496, 2019 Rett’s syndrome – MECP2 mutations NEJM 371:847–858, 2014 Ring chromosome 7, 11 – CALMs, microcephaly, mental retardation Am J Med Genet 30:911–916, 1988; 12 and 15 syndromes JAAD 40:877–890, 1999 Roberts-pseudothalidomide syndrome Syndromes of the Head and Neck, 3rd Edition, p. 735 Rubinstein-Taybi syndrome – large keloids Cutis 57:346–348, 1996; broad thumb Ped Derm 11:21–25, 1994; mental deficiency, small head, broad thumbs and great toes, beaked nose, malformed low-set ears, capillary nevus of the forehead, hypertrichosis of the back and eyebrows, cardiac defects; CREBBP and EP300 mutations Am J Dis Child 105:588–608, 1963; Syndromes of the Head and Neck, 3rd Edition, p. 310 Ruvalcaba syndrome Syndromes of the Head and Neck, 3rd Edition, p. 832 Cleft palate, microcephaly, large ears, short stature (Say syndrome) Syndromes of the Head and Neck, 3rd Edition, p. 559; Humangenetik 26:267–269, 1975 Seckel syndrome – ATR mutations NEJM 371:847–858, 2014; Syndromes of the Head and Neck, 3rd Edition, pp. 313–314 Simplified gyral pattern without syndrome – mutation in TRAPPC9 NEJM 371:847–858, 2014 Smith-Lemli-Opitz syndrome Syndromes of the Head and Neck, 3rd Edition, pp. 890–891 Tetraploidy Syndromes of the Head and Neck, 3rd Edition, p. 96 Tetrasomy 9p syndrome Syndromes of the Head and Neck, 3rd Edition, p. 82 TORCH infections (toxoplasmosis, syphilis, varicella zoster, parvovirus B19, rubella, cytomegalovirus, herpes simplex NEJM 371:847–858, 2014 Trisomy 9 syndrome Syndromes of the Head and Neck, 3rd Edition, p. 83 Trisomy 13 syndrome Syndromes of the Head and Neck, 3rd Edition, p. 443

646 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Trisomy 18 syndrome Syndromes of the Head and Neck, 3rd Edition, p. 95 Trisomy 22 syndrome Syndromes of the Head and Neck, 3rd Edition, p. 95 Velocardiofacial syndrome Syndromes of the Head and Neck, 3rd Edition, p. 740 Weaver-Williams syndrome (cleft palate, microcephaly, mental retardation, musculoskeletal mass deficiency) – long neck Birth Defects 13:69–84, 1977 Williams syndrome Syndromes of the Head and Neck, 3rd Edition, p. 144 Wolf-Hirschhorn syndrome Syndromes of the Head and Neck, 3rd Edition, p. 46 Wrinkly skin syndrome (possibly same as geroderma osteodysplastica) – autosomal recessive; aged appearance with wrinkled skin on the abdomen and dorsal aspects of the hands and feet, increase palmoplantar creases, prominent venous pattern on the chest, intrauterine growth retardation, mental retardation, microcephaly, hypotonia, musculoskeletal abnormalities Ped Derm 25:66–71, 2008; Ped Derm 23:467–472, 2006; Am J Med Genet 101:213–220, 2001; Ped Derm 16:113–117, 1999

MICRONYCHIA AND ANONYCHIA  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – anonychia Graft vs. host disease – onychoatrophy Epidermolysis bullosa acquisita Scleroderma

CONGENITAL DISEASES Congenital hydantoin syndrome Congenital vesicular and erosive dermatosis with supple and reticulated scarring – anonychia JAAD 69:909–915, 2013; AD 121:361–367, 1985

EXOGENOUS AGENTS Parenteral nutrition – extravasation of parenteral nutrition in preterm or low birth weight infants; edema and compartment syndromes; necrosis, acral necrosis, anonychia Ped Derm 32:830–835, 2015

INFILTRATIVE DISEASES Amyloidosis – primary systemic J R Soc Med 8:290–291, 1995

INFLAMMATORY DISEASES Deficiency of interleukin-1 receptor antagonist (DIRA) – autosomal recessive; life-threatening systemic inflammation with bone and skin involvement; anonychia; chronic cutaneous pustulosis resembling

pustular psoriasis; bone lesions include lytic bone lesions, periostitis, osteopenia, long bone epiphyseal ballooning and erosions, widening of clavicle and anterior rib ends, periosteal elevation, heterotopic ossification; vascular occlusions, interstitial pulmonary fibrosis; red eyes AD 148:301–304, 2012 Stevens-Johnson syndrome – anonychia (onychoatrophy) Ped Derm 1:298–300, 1984; AD 113:970, 1977

METABOLIC DISEASES Homocystinuria – arachnodactyly and micronychia Porphyria – congenital erythropoietic porphyria – anonychia Ped Derm 20:498–501, 2003

PRIMARY CUTANEOUS DISEASES Congenital anonychia – autosomal recessive; R-spondin protein mutation (RSPO4) BJD 158:621–623, 2008 Epidermolysis bullosa – absent or dystrophic nails – EBS, superficialis; lethal acantholytic EBS; EBS with plakophilin deficiency; EBS, Dowling-­Meara, EBS other generalized; autosomal recessive EBS; EBS with mottled pigmentation; EBS with muscular dystrophy; JEB with pyloric stenosis, JEB inverse, JEB, late onset, laryngo-onychocutaneous syndrome; DDEB, generalized, RDEB, severe generalized, RDEB, generalized other, DDEB (acral) and RDEB (acral), DDEB (pretibial) and RDEB (pretibial), DEB pruriginosa; RDEB inverse, RDEB centripetalis JAAD 58:931–950, 2008; junctional BJD 170:1056–164, 2014; and dystrophic; anonychia at birth; Herlitz type – anonychia Ped Derm 18:217–222, 2001; dominant dystrophic AD 138:269–270, 2002 Exfoliative dermatitis – anonychia Lethal acantholytic epidermolysis bullosa – autosomal recessive, universal alopecia, cutaneous and mucosal shedding, skin fragility, erythroderma, blistering, anonychia, malformed ears, cardiomyopathy; mutation in desmoplakin (DSP) BJD 162:1388– 1394, 2010; JID 130:2680–2683, 2010; BJD 162:138801394, 2010; Dermatol Clin 28:131–135, 2010; mutation in JUP gene Hum Med Genet 20:1811–1819, 2011 Lichen planus; AD 96:434–435, 1967

SYNDROMES Acrofacial dysostosis Acrogeria – onychoatrophy (anonychia) BJD 142:178–180, 2000; Amniotic bands Anhidrotic ectodermal dysplasia (Clouston syndrome) Cutis 71:224–225, 2003; Anonychia congenita Dermatology 200:84–85, 2001; AD 107:752– 753, 1973 Anonychia of the thumbnails Anonychia with ectrodactyly Anonychia with flexural pigmentation Anonychia with limb defects Anonychia and microcephaly Am J Med Genet 66:257–260, 1996 Anonychia with onychodystrophy, type B brachydactyly, and ectrodactyly Clin Genet 30:219–225, 1986

Micronychia and Anonychia

647

Anonychia with sensorineural hearing loss (DOOR syndrome – deafness, onycho-osteodystrophy, retardation)

Hutchinson-Gilford syndrome (progeria) – small, thin, dystrophic nails Am J Med Genet 82:242–248, 1999; J Pediatr 80:697–724, 1972

Ankyloblepharon-ectrodactyly-cleft lip/palate (AEC) syndrome

Hypoglossia-hypodactylia syndrome Syndromes of the Head and Neck, pp. 666–668, 1990

Apert syndrome Aplasia cutis congenita Syndromes of the Head and Neck, p. 417–419

Idiopathic atrophy of the nails Ped Derm 7:39–41, 1990

Brachydactyly with nail dysplasia – fourth-digit nail absent

Laband syndrome (Zimmermann-Laband syndrome) – gingival fibromatosis, aplasia or dysplasia of fingernails, hypertrophy of the nasal tip and ears, hypermobility, limb asymmetry Am J Med Genet 31:691–695, 1988; Am J Med Genet 25:543–548, 1986

Brachydactyly type A5 – absence of middle and distal phalanges of the hands and feet; fingernail dysplasia 2–5 BJD 152:1339–1342, 2005

Keratosis-ichthyosis-deafness (KID) syndrome

Brachydactyly type B – hypoplasia or absence of distal phalanges 2–5 of the hands, fingernail hypoplasia of 2–5, with lesser affected toes BJD 152:1339–1342, 2005

Nail dysplasia with onychonychia and absence and/or hypoplasia of the distal phalanges

Chromosome type C trisomy

Noonan syndrome

Chromosome 21 long arm deletion syndrome

Oculodentodigital syndrome

Congenital anonychia Ped Derm 31:743–744, 2014

Onychotrichodysplasia with neutropenia

Congenital brachydactyly and nail dysplasia – micronychia and anonychia BJD 152:1339–1342, 2005

Oto-onychoperoneal syndrome Eur J Pediatr 138:317–320, 1982

Coffin-Siris syndrome – anonychia of the fifth finger and toenails Am J Dis Child 132:1044, 1978; micronychia

Scleroatrophic and keratotic dermatosis of the limbs

Congenital onychodysplasia of index fingernails (COIF) (Iso-Kikuchi syndrome) or toenails Ped Derm 25:381–382, 2008; Ped Derm 16:201–204, 1999; Clin Exp Derm 21:457–458, 1996; J Hand Surg 15A:793–797, 1990; AD 119:8–12, 1983; Ann DV 107:431–435, 1980; AD 110:743–746, 1974; Clin Orthop Surg 4:672–677, 1969 Cooks syndrome – hypoplasia/absence of digits 2–5 of the hands and feet; hypoplasia of fingernails 1–3, anonychia 4–5; toenail aplasia BJD 152:1339–1342, 2005 Cornelia de Lange syndrome Am J Med Genet 25:163–165, 1986 Cryptophthalmos syndrome (Fraser) Dyskeratosis congenita Ectrodactyly-ectodermal dysplasia-cleft lip syndrome (EEC syndrome) Clin Genet 3:43–51, 1971 Ellis-van Creveld syndrome (chondroectodermal dysplasia) J Med Genet 17:349–356, 1980 Familial micronychia – personal observation Fetal alcohol syndrome Drug Alcohol Depend 14:1–10, 1984 Fetal hydantoin syndrome Am J Dis Child 127:758, 1974

Nail patella syndrome – micronychia

Rapp-Hodgkin ectodermal dysplasia Triphalangeal thumbs-onychodystrophy-deafness syndrome Trisomy 3q Trisomy 8 Trisomy 13 – hypoplastic toenails; micronychia Trisomy 18 – hypoplasia of the fifth finger and toenails; micronychia Trisomy 21 (Noack’s (Pfeiffer’s) syndrome) – fused digits with micronychia Complete trisomy 22 – primitive low-set ears, bilateral preauricular pit, broad nasal bridge, antimongoloid palpebral fissures, macroglossia, enlarged sublingual glands, cleft palate, micrognathia, clinodactyly of the fifth fingers, hypoplastic fingernails, hypoplastic genitalia, short lower limbs, bilateral sandal gap, deep plantar furrows Pediatrics 108:E32, 2001 Turner’s syndrome Williams’ syndrome Witkop tooth-nail syndrome Oral Pathology, Tiecke RW (ed), McGraw-­Hill, New York, 1965 Yunis-Varon syndrome – dysplastic clavicles, sparse hair, digital anomalies – anonychia Am J Dis Child 134:649–653, 1980

Fetal valproate syndrome Teratology 35:465–474, 1987 Fetal warfarin syndrome – nasal hypoplasia, stippled epiphyses J Pediatr 87:838, 1975 Fryns syndrome (cleft palate, diaphragmatic hernia, coarse facies, acral hypoplasia) – anonychia Clin Genet 35:191–201, 1989

TOXINS Polychlorinated biphenyls – natal teeth, pigment anomalies

Fused digits with micronychia

TRAUMA

Gingival fibromatosis with the ear, nose, bone, nail defects, and hepatosplenomegaly

Onychotillomania

Goltz’s syndrome JAAD 4:273–277, 1981 Hidrotic ectodermal dysplasia Hirschsprung disease with hypoplastic nails and dysmorphic facial features

Physical trauma – anonychia

VASCULAR DISEASES Digital artery occlusion due to emboli – phalangeal necrosis with onychoatrophy

648 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Lymphedema Br J Plast Surg 19:37–42, 1966 Raynaud’s phenomenon – anonychia Umbilical artery catheterization (unintentional) – anonychia, hyponychia, and spontaneous amputation of distal phalanges due to ischemic necrosis BJD 157:1299–1301, 2007

Thyroglossal duct cysts – most common cause of congenital neck mass; on or just lateral to hyoid bone; moves with tongue protrusion

MIDLINE NASAL MASS

 IDLINE FACIAL NODULES M OF CHILDREN

Abscess – nasal vestibule

Ped Derm 23:556–559, 2006

Chordoma

Abscess

Cutaneous T-cell lymphoma Dermatol Online J 15:16, 2018

Angioma

Dermoid cyst – of the septum in adult with columella pit Medicine 97:e13028, 2018; Semin Plast Surg 30:176–180, 2016; Ped Derm 17:62–64, 2000

Dermoid cyst Encephalocele Epidermoid cyst Facial trauma (hematoma, edema) Fibrous dysplasia Hemangioma

Cartilaginous tumor Chondroma J Derm Surg Oncol 16:1025–1036, 1990

Dermoid sinus Ped Radiol 49:1119–1125, 2012 Diffuse large B-cell lymphoma presenting as rhinophyma Cureus 10:e2536, 2018 Encephalocele (anterior encephalocele) Semin Plast Surg 30:176–180, 2016

Infiltrative tumor (rhabdomyosarcoma)

Epidermoid cyst Ped Radiol 42:1119–1125, 2001; AD 127:362–266, 1991

Juvenile xanthogranuloma

Ethmoidal cyst Radiographics 15:27, 1995

Lymphoma

Fibroma

Meningioma

Ganglioneuroma

Metastatic tumor

Glial heterotopia J Plast Reconstr Aesthet Surg 62:695–696, 2009

Nasal glioma

Hemangioma Int Arch Otolaryngol 18:213–216, 2014; Ann Plast Surg 36:586–592, 1996

Histiocytosis

Nasolacrimal duct cyst Neurofibroma Olfactory neuroblastoma Rhabdomyosarcoma Teratoma Trauma Midline developmental anomalies of the neck and chest J Ped Surg Case Reports 2:970–979, 2014 Cutaneous bronchogenic cysts – within the chest or mediastinum, but can be on the neck; midline or lateral; enlarge over time; may drain mucoid material; do not connect with underlying structures Midline cervical cleft – midline ventral neck; small skin tag with linear vertically oriented atrophic patch; at the inferior aspect of the patch is ectopic salivary tissue; associated with cleft lip, cleft palate, mandible, chin, tongue or midline neck hypoplasia

Hemangiopericytoma Arch Otolaryngol Head Neck Surg 124:202– 204, 1998 Lacrimal duct cyst Lipoma Ped Derm 34:e135–136, 2017 Lymphoma Meningocele Meningoencephalocele Eur Arch Otolaryngol 275:2727–2731, 2018 Metastatic carcinoma Midline malignant B-cell lymphoma Cancer 70:2958–2962, 1992 Myxoid malignant fibrous histiocytoma Ear Nose Throat J 91:E3–5, 2012 Nasal glioma (nasal cerebral heterotopia) Semin Plast Surg 30:176–180, 2016; Ear Nose Throat J 80:410–411, 2001 Nasal polyp

Pectus carinatum

Nasoseptal tuberculosis Iran J Otolaryngol 30:231–235, 2018

Pectus excavatum

Natural killer T-cell lymphoma JAMA Otolaryngol Head Neck Surg 145:85–86, 2019; Am J Hematol 92:706–715, 2017

Sternal cleft – rare; partial or total failure of sternal fusion; associated with cardiac and other anomalies  Superior   PHACES   Abdominal raphe  Inferior   Ectopia cordis   Pentalogy of Cantrell (ectopia cordis, intracardiac defect, sternal cleft, omphalocele, pericardial defect)  Complete   Rarely associated with other anomalies (gastroschisis, VACTERL, Dandy-Walker malformation, pectus excavatum, chest wall hamartoma)

Neurilemmoma Ear Nose Throat J 89:221–223, 2010 Neurofibroma Olfactory neuroblastoma Pai syndrome Int J Oral Maxillofac Surg 48:283–290, 2019 Pilomatrixoma JAAD 51:577–579, 2004 Post-transplant lymphoproliferative disorder Ear Nose Throat J Jan 7, 2020 Rhabdomyosarcoma Rhinosporidiosis (Rhinosporidium seeberi) – intranasal and conjunctival red polypoid lesions JAAD 53:931–951, 2005

Milia or Milia-Like Lesions (Fine White Papules) Schwannoma – columellar schwannoma Ear Nose Throat J 88:E38–40, 2009 Teratoma of the nasal tip

649

Sorafenib J Drugs Dermatol 8:573–576, 2009 Voriconazole – pseudoporphyria Int J Dermatol 43:768–771, 2004; Photodermatol Photoimmunol Photomed 23:29–31, 2007

 ILIA OR MILIA-LIKE LESIONS (FINE M WHITE PAPULES)

EXOGENOUS

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

Liquid nitrogen cryotherapy – milia; milia en plaque Dermatol Online J Dec 12, 2014

Calcium JAMA 242:455–456, 1979 Exogenous ochronosis with milia-like lesions

Allergic contact dermatitis Contact Dermatitis 35:49–50, 1996 Anti-p200 pemphigoid Front Immunol Oct 22, 2019

INFECTIONS AND INFESTATIONS

Bullous pemphigoid J Dermatol 41:1003–1005, 2014

Erysipelas, bullous

Epidermolysis bullosa acquisita BJD 171:1022–1030, 2014; BJD 169:100–105, 2013; JAAD 44:818–828, 2001; Cutis 32:521–527, 1983

Herpes simplex infection, resolved

Lichen planus pemphigoides Linear IgA disease Ped Derm 14:303–306, 1997 Lupus erythematosus – bullous LE, resolved JAAD 27:389–394, 1992; Arthritis Rheum 21:58–61, 1978; subacute; discoid LE with milia en plaque BJD 149:424–426, 2003; BJD 137:649–651, 1997; linear cutaneous LE, calcinosis cutis and milia Ped Derm 32:e33– 35, 2015

Herpes zoster scars J Dermatol 23:556–558, 1996 Leishmaniasis – post-treatment BJD 155:860–861, 2006; BJD 156:1088–1089, 2007 Leprosy Int J Lepr Other Mycobact Dis 62:609–610, 1994 Syphilis (congenital syphilis) – palmar and plantar milia JAAD 18:760–771, 1988; Ped Derm 3:395–398, 1986

INFILTRATIVE CONGENITAL Congenital desmoplastic trichoepithelioma Clin Exp Dermatol 32:522–524, 2007 Congenital hemangioma with milia-like structures Ped Derm 15:307–308, 1998 Congenital milia en plaque Ped Derm 33:e258–259, 2016; scalp Indian J Dermatol 60:105, 2015 Congenital persistent milia – associated with transverse nasal groove Dermatology 200:151–152, 2000 Epstein’s pearls (milia) in oral cavity of newborns in mid-palatine raphe; Bohn’s nodules along the alveolar ridge and junction of the hard and soft palate JAAD 59:1050–1063, 2008; pearls of the areolae, scrotum, and labia majora of newborn Milia – profuse familial congenital milia Ped Derm 26:62–64, 2009 Primary milia in infants – occur in 30–40% of full-term infants JAAD 59:1050–1063, 2008; JAAD 23:77–81, 1990; Arch Dis Child 24:286–288, 1949

DRUG-INDUCED

Amyloidosis, bullous – healing phase AD 124:1683–1686, 1988; localized axillary milia en plaque Clin Exp Dermatol 41:764–767, 2016; poikiloderma-­like cutaneous amyloidosis and generalized milia J Dermatol 44:476–477, 2017 Mucinosis – plaque-like erythema with milia in renal transplant patient JAAD 39:334–347, 1998 Congenital self-healing Langerhans cell histiocytosis (Hashimoto-­ Pritzker disease) – anetoderma-like lesions with milia J Pediatr Hematol Oncol 25:270–273, 2003

METABOLIC Calcinosis cutis (pseudomilia) (milia-like calcinosis cutis) AD 142:1237–1238, 2006; Ped Derm 21:483–485, 2004; JAAD 45:152–153, 2001; Eur J Dermatol 10:637–638, 2000; perforating calcinosis cutis J Cutan Pathol 8:247–250, 1981; calcinosis cutis of the penile shaft Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 61; periorbital Clin Exp Dermatol 37:787–788, 2012; generalized milia-like idiopathic calcinosis Chylous reflux JAAD 55:1108–1109, 2006 Gout – milia-like tophi Clin Exp Dermatol 38:622–625, 2013

Acitretin JAAD 37:353–356, 1997; Acta DV 73:235, 1993

Oxalosis JAAD 31:368–372, 1994

Benoxaprofen – pseudoporphyria J R Soc Med 76:525–527, 1983; BJD 106:613, 1982

Porphyria – hepatoerythropoietic porphyria AD 138:957–960, 2002; porphyria cutanea tarda – vesicles, bullae, crusts, skin fragility, atrophic scars, milia NEJM 369:1356, 2013; variegate porphyria – as in PCT; pseudoporphyria Mayo Clin Proc 76:488–492, 2001; congenital erythropoietic porphyria – onycholysis, milia of the nose, facial hypertrichosis, bullae of the hand, hyper- and hypopigmentation with scarring Ped Derm 35:833–834, 2018; BJD 171:422–423, 2014; late-onset congenital erythropoietic porphyria (uroporphyringen II synthase) – erosions, milia, crusts BJD 175:1346–1350, 2016

Corticosteroids, topical JAAD 21:215–217, 1989; AD 122:139–140, 1986 Cyclosporine Dovitinib Dermatol Online J Sept 17, 2015 5-Fluorouracil Isotretinoin – eruptive milia Ped Derm 34:728–729, 2017 Penicillamine dermopathy; AD 125:92–97, 1989; penicillamine-­ associated cutis laxa and milia en plaque Dermatol Online J 15:22, 2016

Uremia – uremic frost

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Vitamin D-dependent rickets type IIA – autosomal recessive; hair present at birth then lost in the first 12 months; forehead milia; clinically and histologically similar to atrichia with papular lesions Ped Derm 29:527–529, 2012; AD 141:343–351, 2005

NEOPLASTIC Basaloid follicular hamartoma – yellow plaque with milia AD 129:915–917, 1993 Desmoplastic trichoepithelioma – personal observation Eruptive vellus hair cysts Generalized follicular hamartoma AD 131:454–458, 1995 Lipoblastomas – multiple subcutaneous nodules with overlying hyperpigmentation, milia, and hypertrichosis Ped Derm 34:180–186, 2017; BJD 143:694, 2000 Lymphoma – CTCL JAAD 50:368–374, 2004; large milia with facial alopecia – folliculotropic cutaneous T-cell lymphoma AD 144:738– 746, 2008; pilotropic (follicular) cutaneous T-cell lymphoma J Cut Pathol 42:90–101, 2015; AD 146:607–613, 2010; BJD 141:315– 322, 1999; AD 132:683–687, 1996 Milia, including multiple eruptive milia – face, earlobe Rook, p. 1669, 1998, 6th Edition; Ped Derm 16:108–110, 1999; JAAD 37:353–356, 1997; Cutis 60:183–184, 1997; Clin Exp Dermatol 21:58–60, 1996 Nevus depigmentosus with milia JAAD 59:1050–1063, 2008; BJD 132:317–318, 1995 Pilomatrixomas – multiple eruptive pilomatrixomas Ped Derm 10:382–384, 1993 Squamous cell carcinoma – multiloculated milia Cutis 89:45–47, 2012 Steatocystomas of the eyelid – personal observation Syringomas – familial syringomas JAAD 20:702–703, 1989; milia-like syringomas Ped Derm 21:269–271, 2004; JAAD 16:310– 314, 1987; eruptive syringomas associated with milia Int J Derm 34:193–195, 1995; perianal milia-like syringomas Dermatology 191:249–251, 1995; syringomas with calcinosis cutis JAAD 23:372–375 Trichoepitheliomas – linear facial plaque with milia – AAD '97, Ped Derm section

PHOTODERMATOSES Chronic actinic damage Favre-Racouchot JAMA Derm 254:623–625, 2018; The Dermatologist March 2018, pp47–50 Polymorphic light eruption Photodermatol Photoimmunol Photomed 25:51–52, 2009 Reaction to photodynamic therapy Actas Dermosifiliogr 110:71–74, 2019

epidermolysis bullosa) – hypopigmented patches; giant bullae of the hand and foot; erosions, tongue erosions, milia Ped Derm 30:736– 740, 2013; Ped Derm 20:535–537, 2003; J Cutan Pathol 18:328– 332, 1991; JAAD 21:708–713, 1989; AD 121:1429–1438, 1985 Darier’s disease Epidermolysis bullosa – EBS superficialis, EBS Dowling-Meara, EBS other generalized; EBS with muscular dystrophy, JEB Herlitz type, JEB non-Herlitz type generalized, JEB non-Herlitz type localized; JEB with pyloric atresia, JEB inversa; laryngo-onychocutaneous syndrome; DDEB generalized, RDEB, severe generalized, RDEB generalized other; DDEB (acral) and RDEB (acral); DDEB (pretibial) and RDEB (pretibial); DEB pruriginosa; RDEB inversa, RDEB centripetalis JAAD 58:931–950, 2008 Epidermolysis bullosa – dominant dystrophic JID 112:815–817, 1999; generalized atrophic benign epidermolysis bullosa AD 122:704–710, 1986; autosomal recessive epidermolysis bullosa simplex AD 125:931–938, 1989; Dowling-Meara EB Cutis 70:19–21, 2002; AD 122:190–198, 1986; dystrophic epidermolysis bullosa inversa – flexural bullae, oral ulcers, dental caries, milia Ped Derm 20:243–248, 2003; epidermolysis bullosa pruriginosa – reticulate scarring, dermatitis with lichenified plaques, violaceous linear scars, albopapuloid lesions of the trunk, prurigo nodularis-like lesions, milia BJD 152:1332–1334, 2005; transient bullous dermolysis of the newborn JAAD 58:1050–1063, 2008; epidermolysis bullosa pruriginosa – autosomal dominant or autosomal recessive; vesicles, erosions, crusting, hypertrophic scars Dermatol Ther 32:e13035, 2019; dystrophic form of epidermolysis bullosa; mutation in COL7A1 AD 147:956–960, 2011 Eruptive milia Cutis 91:191–192, 2013; JAAD 59:1050–1063, 2008; Ped Derm 25:474–476, 2008; AD 144:816–817, 2008; JAAD 37:353–356, 1997   Eruptive milia seen in Cutis 91:191–192, 2013   Bazex syndrome   Brooke-Spiegler syndrome   Nevoid basal cell carcinoma   Rombo syndrome Granuloma annulare – mimicking milia (personal observation) Lichen planus Clin Exp Dermatol 24:266–269, 1999; bullous lichen planus; lichen planus follicularis tumidus with milia and comedones Clin Exp Dermatol 17:346–348, 1992 Lichen planus follicularis tumidus – brown-violaceous acral plaques, cysts, milia, comedonal openings Clin Exp Dermatol 45:638–641, 2020 Lichen sclerosus et atrophicus, bullous Clin Exp Dermatol 39:400– 401, 2014; BJD 92:711–714, 1975 Milia en plaque Ped Derm 26:717–720, 2009; JAAD 59:1050–1063, 2008; Derm Surg 28:291–295, 2002; Int J Derm 39:614–615, 2000; Clin Exp Dermatol 24:183–185, 1999; Cutis 22:67–70, 1978; multiple milia overlying hyperpigmented patch BJD 157:1287–1289, 2007; earlobes, post-auricular area Bull Soc Franc Derm Syph 14:361, 1903; of ears Ped Derm 29:504–506, 2012 Nodular grouped milia JAAD 59:1050–1063, 2008

PRIMARY CUTANEOUS DISEASES

Osteomas – multiple facial, in older women with longstanding acne J Eur Acad DV 20:321–326, 2006; Cutis 69:383–386, 2002

Acne-associated milia

Primary milia AD 135:1545, 1548, 1999; of children and adults JAAD 59:1050–1063, 2008

Alopecia mucinosa (follicular mucinosis) Atrichia with papular lesions – milia of the ears and face AD 141:343–351, 2005 Atrophoderma vermiculata Z Hautkr 56:1473–1477, 1981 Transient bullous dermolysis of the newborn (form of autosomal dominant epidermolysis bullosa or recessive dystrophic

Transverse nasal line with congenital persistent milia embryonic fault line AD 148:1037–1039, 2012; Dermatology 200:151–152, 2000; Clin Exp Derm 18:289–290, 1993; AD 84:316–317, 1961; AD 63:70–72, 1951 Vulvar milia J Dermatol 23:427–428, 1996

Milia or Milia-Like Lesions (Fine White Papules)

SYNDROMES Absent dermatoglyphics and transient facial milia JAAD 32:315– 318, 1995 Anhidrotic ectodermal dysplasia – milia-like lesions with enlarged sebaceous glands on biopsy BJD 149:443–444, 2003 Atrichia with papular lesions – autosomal recessive; hypopigmented white streaks of the scalp Ped Derm 29:527–529, 2012; JAAD 59:1050–1063, 2008 Bart’s syndrome with germ line mosaicism Basaloid follicular hamartoma syndrome – autosomal dominant; milia, comedone-like lesions, dermatosis papulosa nigra, skin tag-like lesions, hypotrichosis, multiple skin-colored, red, and hyperpigmented papules of the face in periorificial distribution, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes); hypohidrosis Ped Derm 25:474–476, 2008; AD 144:933–938, 2008; Cutis 78:42–46, 2006; JAAD 49:698–705, 2003; BJD 146:1068–1070, 2002; JAAD 45:644–645, 2001; JAAD 43:189–206, 2000; JAAD 27:237–240, 1992 Basan syndrome (ectodermal dysplasia) – congenital facial milia, nail dystrophy, progressive palmoplantar callosities, absent dermatoglyphics; transient neonatal acral bullae Ped Derm 29:684–685, 2012; Ped Derm 29:527–529, 2012; JAAD 32:315– 318, 1995; J Pediatr 64:621–631, 1964 Bazex-Dupre-Christol syndrome – X-linked dominant; follicular atrophoderma, multiple milia, congenital hypotrichosis, hypohidrosis, multiple basal cell carcinomas from puberty onward Ped Derm 29:527–529, 2012; Ped Derm 25:112–113, 2008; J Med Genet 33:493–497, 1996; JAAD 59:1050–1063, 2008; Ped Derm 25:474– 476, 2008; AD 130:337–342, 1994; Ped Derm 16:108–110, 1999; Clin Exp Dermatol 6:31–41, 1981; Ann Dermatol Syphilgr (Paris) 93:241–254, 1966 Bazex-Dupre-Christol-like syndrome – autosomal dominant; basal cell carcinomas, hypohidrosis, congenital hypotrichosis, multiple milia, follicular atrophoderma Ped Derm 28:727–728, 2011; Derm Surg 26:152–154, 2000; AD 130:337–342, 1994 Brooke-Spiegler syndrome Ped Derm 29:527–529, 2012; JAAD 59:1050–1063, 2008 Congenital hypotrichosis and milia Am J Med Genet 56:423–424, 1995 Down’s syndrome – idiopathic milia-like calcinosis cutis Ped Derm 30:263–264, 2013; Ped Derm 19:271–273, 2002; JAAD 45:152– 153, 2001; BJD 134:143–146, 1996; JAAD 32:129–130, 1995; AD 125:1586–1587, 1989; perforating milia-like calcinosis with syringomas in Down’s syndrome J Cosmetic Dermatol 19:102–104, 2020; Ped Derm 11:258–260, 1994 Ectodermal dysplasia, absent dermatoglyphics, nail changes, simian crease, milia Ped Derm 25:474–476, 2008 Extensive reticular hyperpigmentation and milia Ped Derm 16:108–110, 1999 Familial milia and absent dermatoglyphics – digital flexion contractures, webbed toes, palmoplantar hypohidrosis, painful fissured calluses, acral blistering, simian crease JAAD 59:1050–1063, 2008 Familial multiple eruptive milia Birth Defects 7:333–337, 1971; Ped Derm 16:108–110, 1999 Follicular atrophoderma (perioral, pigmented), milia, and epidermoid cysts Ped Derm 25:474–476, 2008 Gardner’s syndrome Ped Derm 25:474–476, 2008

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Hereditary perioral pigmented follicular atrophoderma with milia-like epidermoid cysts BJD 139:713–718, 1998 Hereditary vitamin D-dependent rickets type IIA (autosomal recessive) – milia resolves with pitted scars JAAD 59:1050–1063, 2008 Hypotrichosis with light-colored hair and facial milia Ped Derm 16:108–110, 1999 Keratitis, ichthyosis, deafness (KID) syndrome – multiple milia of the nose, cheeks, and ears; red face with papillomatous hyperkeratosis of the face, scalp, trunk, and extremities Ped Derm 29:527–529, 2012; Ped Derm 23:81–83, 2006 Kindler’s syndrome JAAD 59:1050–1063, 2008 Loeys-Dietz syndrome – autosomal dominant; TGFBR1 or TGFBR2 (transforming growth factor beta receptor genes); Marfanoid habitus, delicate triangular face, multiple facial milia, velvety and translucent skin, easy bruising, varicose veins, atrophic scars, malar hypoplasia, retrognathia, craniosynostosis, hypertelorism, cleft lip and palate, bifid uvula, malar hypoplasia, blue sclerae, arachnodactyly, joint laxity, pectus deformities, scoliosis, camptodactyly, high-arched palate, aortic root aneurysm and dissection, arterial tortuosity AD 147:223–226, 2011; JAAD 59:1050–1063, 2008; JAAD 55:S41–45, 2006; Nature Genet 37:275–281, 2005 Marie-Unna-type congenital hypotrichosis (congenital hereditary trichodysplasia) – autosomal dominant; sparse or absent hair at birth; hair becomes wavy and coarse, then lost from puberty onward; congenital milia-like lesions JAAD 59:1050–1063, 2008; Milia with nodular calcinosis and palmoplantar keratoderma Ann Dermatol Venereol (Paris) 107:273–277, 1980 Multiple follicular hamartomas with sweat gland and sebaceous differentiation, vermiculate atrophoderma, milia, hypotrichosis, and late development of basal cell carcinomas JAAD 39:853– 857, 1998 Multiple trichoepitheliomas, cylindromas, and milia Ann DV 114:175–182, 1987 Nevoid basal cell carcinoma syndrome – milia of face Ped Derm 29:527–529, 2012; BJD 164:245–256, 2011; JAAD 59:1050–1063, 2008; BJD 145:508–509, 2001; JAAD 42:939–969, 2000; with palmar epidermoid cyst, milia, and maxillary cysts BJD 145:508– 509, 2001 Nicolau and Balus syndrome – syringomas, milia, and atrophoderma vermiculata Ped Derm 29:527–529, 2012; Dermatologica 162:281–286, 1981 Oral-facial-digital syndrome type 1 (Papillon-Leage-Psaume syndrome) – X-linked dominant; congenital facial milia which resolves with pitted scars; milia of the face, scalp, pinnae, and dorsal hands; short stature, hypotrichosis with dry and brittle hair, short upper lip, hypoplastic ala nasi and lower jaw, pseudoclefting of the upper lip, hooked pug nose, hypertrophied labial frenula, bifid or multilobed tongue with small white tumors within clefts, ankyloglossia, multiple soft hamartomas of oral cavity, clefting of the hard and soft palate, teeth widely spaced with dental caries, trident hand or brachydactyly, syndactyly, clinodactyly, ulnar deviation of the index finger, or polydactyly; hair dry and brittle, alopecic, numerous milia of the face, ears, backs of the hands, mental retardation with multiple central nervous system abnormalities, frontal bossing, hypertelorism, telecanthus, broad depressed nasal bridge; polycystic renal disease; combination of polycystic renal disease, milia, and hypotrichosis is highly suggestive of OFD 1 Ped Derm 29:527–529, 2012; Ped Derm 27:669–670, 2010; JAAD 59:1050–1063, 2008; Ped Derm 25:474–476, 2008; Ped Derm 9:52–56, 1992; Am J Med Genet 86:269–273, 1999; JAAD

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31:157–190, 1994; Ped Derm 9:52–56, 1992; Pediatrics 29:985– 995, 1962; Rev Stomatol 55:209–227, 1954

Amyloidosis, primary systemic – with multiple myeloma; parotid gland enlargement

Pachyonychia congenita, Jackson-Lawler type (type 2) – white milia-like cysts at birth Ped Derm 29:527–529, 2012; JAAD 59:1050–1063, 2008; JAAD 38:1007–1009, 1998

Cold agglutinin disease – painful erythema and edema of the ears; thrombotic vasculopathy JAMADerm 151:785–786, 2015

Persistent milia, steatocystoma multiplex and eruptive vellus hair cysts within a family Dermatology 196:392–396, 1998 Pseudoxanthoma elasticum with milia en plaque J Cutan Pathol 24:61–63, 1997 Rasmussen syndrome (variant of Brooke-Spiegler syndrome) – trichoepitheliomas, milia, and cylindromas AD 111:610, 1975; with palmoplantar keratoderma Ped Derm 16:108–110, 1999 Reticular pigmented genodermatosis with milia (NaegeliFranceschetti-­Jadassohn syndrome) Clin Exp Dermatol 20:331– 335, 1995 Rombo syndrome – milia-like papules and cysts of the face and trunk, basal cell carcinomas, vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, peripheral vasodilatation with cyanosis JAAD 59:1050–1063, 2008; Ped Derm 25:474–476, 2008; BJD 144:1215–1218, 2001; JAAD 39:853–857, 1998; Acta DV 61:497–503, 1981 Trichoepitheliomas and milia Ped Derm 16:108–110, 1999 Trisomy 13 – total body milia; polydactyly, congenital cystic adenomatoid malformation, pulmonary hypertension, apnea, atrial septal defect, umbilical hernia, epilepsy, dislocated hip joint, ocular hypertelorism, microphthalmia, retinal hypoplasia, irideremia, small ears, deafness, broad flat nose, cleft palate, micrognathia, mental retardation Ped Derm 27:657–658, 2010

TOXINS Agent orange JAAD 74:143–170, 2016

TRAUMA Autologous skin transplants Br J Plast Surg 6:153, 1950 Burns, second degree Carbon dioxide laser resurfacing Dermabrasion J Derm Surg Oncol 14:1301, 1988; AD Syphilol 68:589, 1953 Physical trauma Post-radiation therapy Actas Dermosifiliogr 107:156–158, 2016 Surgical scar Tattoo Cutis 87:195–196, 2011 X-rays

VASCULAR LESIONS Congenital hemangioma with milia-like structures Ped Derm 15:307–308, 1998

Cryofibrinogenemia – ischemia, purpura, livedo reticularis, ulcers, necrosis, gangrene Rheum 47:205–207, 2008 Cryoglobulinemic purpura; leukocytoclastic vasculitis Autoimmun Rev 17:457–464, 2018 Crystalglobulins JAAD 77:1145–1158, 2017 Crystal storing histiocytosis – facial edema Cutis laxa – heavy-chain deposition disease JAMADerm 150:1192– 1196, 2014 Gamma heavy-chain disease – vascular nodules JAAD 23:988– 991, 1990 Heavy-chain disease (Franklin’s disease) AD 124:1538–1540, 1988 Hyper IgE syndromes (Job’s, Buckley’s, Quie-Hill syndromes (allergic rhinitis)) Dermatol Therapy 18:176–183, 2005;; Ned Tijdschr Geneeskd 138:526–528, 1994 Intravascular reactive glomeruloid angioendotheliomatosis Kahler’s disease – periodic fever, oral aphthae, morbilliform eruption, red macules or papules, urticaria, annular erythema, red nodules, arthralgias, abdominal pain, lymphadenopathy; combinations of fever, arthritis, and rash, annular erythema, and pustules AD 136:1487–1494, 2000; Ann DV 123:314–321, 1996; AD 130:59–65, 1994 Hyper IgM syndrome (hypogammaglobulinemia with hyper IgM) – X-linked with mutation in CD40 ligand gene; low IgA and IgG; sarcoid-­like granulomas; multiple papulonodules of the face, buttocks, arms Ped Derm 21:39–43, 2004; Bolognia, p. 845, 2003; Ped Derm 18:48–50, 2001; ulcers of palate, tongue, buccal mucosa, and lips JAAD 38:191–196, 1988 IgA benign monoclonal gammopathy – violaceous nodules JAAD 21:1303–1304, 1989 IgA gammopathy  Associations:   Erythema elevatum diutinum Australas J Dermatol 36:21–23, 1995    Pyoderma gangrenosum Clin Exp Dermatol 34:46–48, 2009; Australas J Dermatol 36:21–23, 1995   Subcorneal pustular dermatosis BJD 176:1341–1344, 2017; Clin Exp Dermatol 34:46–48, 2009; Clin Exp Dermatol 33:229–233, 2008; J Dermatol 31:661–665, 2014; Dermatol187:124–126, 1993    Sweet’s syndrome Rinsho Ketsueki 42:1176–1180, 2001; Australas J Dermatol 36:21–23, 1995   Urticarial vasculitis BJD 102:355–357, 1980   Urticaria-like neutrophilic dermatosis – annular urticarial plaques without scale – IgA gammopathy BJD 170:1189–1191, 2014; Medicine (Balt)88:23–31, 2009 Lambda light-chain vasculopathy – purpura Monoclonal plasmacytic ulcerative stomatitis Oral Surg Oral Med Oral Pathol 75:483–487, 1993

MONOCLONAL GAMMOPATHY, CUTANEOUS MANIFESTATIONS

Myeloma – hyperkeratotic filiform follicular spicules J Cut Pathol 46:844–851, 2019; JAAD 49:736–740, 2003; JAAD 36:476–477, 1997; cutaneous crystalline deposits AD 130:484–488, 1994; follicular spicules associated with myeloma with monoclonal type 1 cryoglobulins AD 145:479–484, 2009

AESOP (adenopathy, extensive skin patch overlying a plasmacytoma) Medicine 82:51–59, 2003

Necrobiotic xanthogranuloma with paraproteinemia Semin Cut Med Surg 26:108–111, 2007

Acquired angioneurotic edema Europ J Int Med 20:457–461, 2009

Mucinoses Normolipemic plane xanthomas – with multiple myeloma; benign monoclonal gammopathies – normolipemic plane xanthomas JAAD 49:119–122, 2003 Paroxystic capillary leak syndrome – usually IgG kappa Am J Med 103:514–519, 1997 Plasmacytosis – benign primary cutaneous plasmacytosis (plasmacytoma) AD 145:299–302, 2009 POEMS syndrome Am J Hematol 92:814–829, 2017; Blood Rev 21:285–299, 2007 Rosai-Dorfman disease, cutaneous Am J Dermatopathol 39:776– 781, 2017 Schnitzler’s syndrome – chronic urticaria, intermittent fever, and IgM monoclonal gammopathy (macroglobulinemia), high ESR, leukocytosis, arthralgia, arthritis, with disabling bone pain (osteosclerotic) of distal femur and proximal tibia, palpable lymphadenopathy, hepatosplenomegaly JAAD 68:834–853, 2013; AD 143:1046–1050, 2007; JAAD 56:S120–122, 2007; J Eur Acad Dermatol Venereol 16:267–270, 2007; BJD 142:954–959, 2000; JAAD 30:316–318, 1994; AD 130:1193–1198, 1994; JAAD 20:855–857, 1989; JAAD 20:206–211, 1989

LOCALIZED Acral persistent papular mucinosis JAAD 21:293, 1989 Angiomyxoma – multiple lesions may indicate Carney complex Ped Derm 20:230, 2003 Congenital linear cutaneous mucinosis of infancy Int J Dermatol Dec 23, 2019; AD 122:790, 1986 Cutaneous focal mucinosis (digital mucous or myxoid cyst, extradigital cutaneous myxoma) G Ital DV 153:847–854, 2018 Cutaneous mucinosis of infancy (atypical papular mucinosis of infancy) Dermatol Online J Oct 15, 2018; JAAD 24:265–270, 1991 Carney complex – cutaneous myxomas, spotty pigmentation, endocrine overactivity; blue nevi café au lait macules Eur J Endocrinol 173:M85–87, 2015; AD 122:790, 1986 Discrete papular lichen myxedematosus Cutis 75:105–112, 2005 Juvenile hyaline fibromatosis Follicular mucinosis (alopecia mucinosa) BJD 182:29–38, 2020; JAAD 80:1704–1711, 2019 Lipoid proteinosis

Scleromyxedema Case Rep Dermatol 11:168–175, 2013

Mucinous eccrine nevus Clin Exp Derm 38:1–4, 2013

Sweet’s syndrome Eur J Int Med 20:457–461, 2009

Mucinous nevus BJD 182:7–8, 2020; Ped Derm 20:230, 2003

TEMPI syndrome – telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting NEJM 367:778–780, 2012; NEJM 366:1843–1845, 2012; NEJM 365:475–477, 2011

Neuropathia mucinosa cutanea Ped Derm 20:230, 2003

Urticaria-like neutrophilic dermatosis – annular urticarial plaques without scale – IgA gammopathy BJD 170:1189–1191, 2014; Medicine (Balt) 88:23–31, 2009

Nevoid follicular mucinosis J Cut Pathol 40:844–847, 2013 Nodular lichen myxedematosus Cutis 75:105–112, 2005 Pachydermoperiostosis Plaque-like cutaneous mucinosis AD 130:1433–1438, 1994 Pretibial myxedema JAAD Case Rep 4:874–876, 2018

Waldenstrom’s macroglobulinemia – neoplastic B-cell infiltrates; red-brown or violaceous papulonodules (cutaneous macroglobulinosis) Ann DV 129:53–55, 2002; JAAD 45:S202–206, 2001; Ann DV 112:509–516, 1985; crusted papules AD 128:372– 376, 1992; pruritic papules and plaques Ann Dermatol 30:87–90, 2018

Proximal acral papular mucinosis

Waldenstrom’s IgM storage papules – skin-colored translucent papules on extensor extremities, buttocks, trunk; may be hemorrhagic, crusted, or umbilicated JAAD 45:S202–206, 2001; nodular macroglobulinosis JAAD 77:1145–1158, 2017

SECONDARY

X-linked hyper IgM syndrome treated with G-CSF – disseminated pyogenic granulomas JAAD 49:105–108, 2003

Discrete papular mucinosis with Hashimoto’s thyroiditis Cutis 7:143–145, 2011

Xanthoma disseminatum – yellow cobblestoned papules and plaques in intertriginous areas; monoclonal gammopathy JAMA Derm 152:715–716, 2016

Eosinophilia-myalgia syndrome associated with l-tryptophan ingestion

MUCINOSES PRIMARY GENERALIZED Hereditary progressive mucinous histiocytosis AD 130:1300, 1994 Lichen myxedematosus (scleromyxedema) Mucopolysaccharidoses – Hunter’s, Hurler’s, Scheie, Sly syndromes BJD e329, 2018; Ped Derm 33:594–601, 2016 Myxedema (generalized, pretibial) Scleredema adultorum BJD 182:29–38, 2020

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Reticular erythematous mucinosis Acta DV Croat 27:16–21, 2019 Self-healing juvenile cutaneous mucinosis BJD 182:29–38, 2020; Am J Case Rep 20:65–69, 2019

Degos’ disease Dermatomyositis Case Rep Dermatological Medicine 2014:938414

Fibrocystic-histiocytic proliferations (dermatofibroma, fibromatosis, nodular fasciitis, atypical fibroxanthoma) Granuloma annulare HIV disease and papular mucinosis AD 128:996–997, 1992 Hypothyroidism – focal mucinosis Cutis 32:449, 1983 Localized papular mucinosis with IgA nephropathy JAMA Derm 147:599–602, 2011 Jessner’s lymphocytic infiltrate Lupus erythematosus – papulonodular mucinosis associated with systemic lupus erythematosus Am J Dermatopathol Sept 19, 2019; plaque-like cutaneous lupus mucinosis Acta DV Feb 5, 2020; AD 129:383, 1993; tumid lupus Stat Pearls Sept 12, 2019; atypical nodular mucinosis of lupus Medicine 96:e8391, 2017 Mixed connective tissue disease Annis Bras Dermatol 88:635–638, 2013

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Mucinosis of obesity (localized lichen myxedematosus (papular mucinosis) in morbid obesity) Dermatopathol (Basel)5:1620, 2018; BJD 148:165–168, 2003 Neoplasms (neurofibroma, neurilemmoma, adenoid basal cell carcinoma, adnexal carcinomas) Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) Am J Med 114:563–572, 2003; scleromyxedema-like cutaneous disease in renal dialysis patients Lancet 356:1000–1001, 2000 Plaque-like mucinosis, paraneoplastic; lung adenocarcinoma J Cut Pathol 45:305–307, 2018 Toxic oil syndrome – ingestion JAAD 16:139–140, 1987 Ultraviolet light and PUVA therapy

MUCOCUTANEOUS CANDIDIASIS SYNDROMES JAAD 73:367–381, 2015 Autoimmune polyendocrinopathy, candidiasis, and ectodermal dysplasia (APECED) – autosomal recessive, (APS-1 syndrome) hypoparathyroidism, Addison’s disease, chronic mucocutaneous candidiasis; autoimmune hepatitis, vitiligo, alopecia areata; autoantibodies to IL-17A, 17F, IL-22; Th 17 cytokines; mutation in AIRE JAAD 73:367–381, 2015 CARD 9 deficiency – autosomal recessive, chronic mucocutaneous candidiasis; candida meningitis JAAD 73:367–381, 2015 Dectin-1 mutation – autosomal recessive; chronic mucocutaneous candidiasis; C-type lectin domain family; vulvar and oropharyngeal candidiasis JAAD 73:367–381, 2015

MUSCLE WEAKNESS AND RASH  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Activated STING in vascular and pulmonary syndrome (stimulator of interferon genes) –associated vasculopathy) – autoinflammatory disease; butterfly telangiectatic facies; acral violaceous psoriasiform, papulosquamous and atrophic vasculitis of hands; progressive digital necrosis, swelling of fingers, amputation of several digits, violaceous and telangiectatic malar plaques, nasal septal destruction, chronic leg myalgias, atrophic skin over the knees, red-purpuric plaques over cold-sensitive areas (acral areas) (cheeks, nasal tip, ears), reticulate erythema of arms and legs; nodules of the face, nose, and ears; fingertip ulcers with necrosis; nail dystrophy; interstitial lung disease with fibrosis; polyarthritis; myositis JAAD 74:186–189, 2016; NEJM 371:507–518, 2014 Adenosine deaminase 2 deficiency J Clin Immunol 38:569–578, 2018 Chronic graft vs. host disease Muscle Nerve 40:643–647, 2009 Dermatomyositis – centripetal flagellate erythema NEJM 370:2327– 2337, 2014; J Drugs in Dermatol 10:902–904, 2011; J Rheumatol 26:692–695, 1999; Clin Exp Dermatol 21:440–441, 1996; Wongtype dermatomyositis; unilateral eyelid edema, anti-MDA5 Ophthalmol Plastic Reconstr Surg 34:e209–211, 2018; erythrodermic and extensive poikiloderma J Med Case Rep 12:83, 2018 Hyper-IgD syndrome – myositis and myalgias; recurrent transient and fixed pink plaques and nodules of the face and extremities; cephalic pustulosis; mevalonate kinase deficiency Ped Derm 35:482–485, 2018

Gain of function STAT1 mutations – chronic mucocutaneous candidiasis; onychodystrophy, generalized dermatophytosis; disseminated coccidioidomycosis, histoplasmosis, sinopulmonary infections, herpes simplex infections; endocrine, dental, gastrointestinal disease; diabetes mellitus, hypothyroidism, autoimmune hepatitis, cerebral aneurysms, oral and esophageal squamous cell carcinomas; increased levels of interferon results in decreased IL-17A and IL-22 Oral Dis 25:684–692, 2019; JAAD 73:367–381, 2015;

IgG4-related disease NEJM 373:1762–1772, 2015

Hyper IgE syndrome – autosomal dominant; STAT3 mutation, chronic mucocutaneous candidiasis Clin Trans Immunology 5:e114, 2016

Systemic lupus erythematosus J Pak Med Assoc 67:1180–1185, 2017

Mixed connective tissue disease – anti-U1RNP antibody Rheum 16:328–334, 1981 Necrotizing autoimmune myositis – anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody; heliotrope BMJ Case Rep April 16, 2019 Pemphigus foliaceus Australas J Dermatol 58:e120–122, 2017 Pemphigus vulgaris – with thymoma and myasthenia gravis

IL-17RA, IL-17, ACT-1 associated with chronic mucocutaneous candidiasis – autosomal recessive JAAD 73:367–381, 2015

DEGENERATIVE DISORDERS

PGM3 deficiency – autosomal recessive; dermatitis, conductive hearing loss, ataxia, myoclonus, narrow palpebral fissures; increased IgE; herpes simplex, molluscum contagiosum viral infections, sinopulmonary infections, chronic mucocutaneous candidiasis, developmental delay JAAD 73:367–381, 2015

Pseudohernia – flaccid paralysis of abdominal musculature; diabetic radiculoneuropathy, poliomyelitis, ventral nerve root damage from intradural tumor excision, Lyme disease, syringomyelia, prolapsed intravertebral disk; must be differentiated from true abdominal hernia JAMA 310:639–640, 2013; Hernia 10:364–366, 2006

PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – autosomal dominant; evaporative cold urticaria; neonatal ulcers in cold sensitive areas (acral areas and nasal inflammatory lesions); granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of the nose with nasal destruction; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of the cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAAD 73:367–381, 2015; JAMADerm 151:627–634, 2015

Werdnig-Hoffmann spinal muscular atrophy – multilobulated tongue, tongue fasciculations

DRUG REACTIONS Acetylcholinesterase inhibitors – pesticide exposure J Expo Sci Environ Epidemiol 20:571, 2010 Atorvastatin – weakness, myopathy, dysphagia; statin-induced autoimmune myopathy; antibodies to HMGCR NEJM 275–283, 2019

Muscle Weakness and Rash DRESS (drug rash with eosinophilia and systemic symptoms) syndrome – celecoxib and anti-tuberculosis drugs J Korean Med Sci 23:521–525, 2008; meningitis, encephalitis, cerebral vasculitis, SIADH; headache, seizure, coma, speech abnormalities, cranial nerve palsies, muscle weakness Intern Med 52:1403–1405, 2013; Ann Neurol 51:771–774, 2002

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Louse-borne relapsing fever (Borrelia recurrentis) – high fever, headache, dizziness, myalgias, fatigue, hemorrhage, liver disease, renal failure; relapse ever 7–19 days JAAD 82:551–569, 2020 Lyme disease – dermatomyositis-like rash Cureus 10:e2608, 2019 Malaria (Plasmodium falciparum) – fever, headache, myalgias NEJM 373:1060–1067, 2015; Parasitol Res 110:1–18, 2012 Rheumatic fever Rheumatology (Oxford). 2010; Nov 3

INFECTIONS AND INFESTATIONS African trypanosomiasis (African sleeping sickness) Acta Trop 101:31–39, 2007 Bartonellosis – Bartonella bacilliformis; bacillary angiomatosis; Andes mountains, Peru, Colombia, Ecuador; Oroya fever with verruga peruana; sandflies and fleas as vectors; red papules in crops become nodular, hemangiomatous or pedunculated; face, neck, extremities, mucosal lesions; 1–4 mm pruritic red papules; massive hemolytic anemia, high fever, muscle pain, delirium, coma JAAD 59:179–1206, 2008; JAAD 54:559–578, 2006; Clin Inf Dis 33:772–779, 2001; Ann Rev Microbiol 35:325–338, 1981 Candida albicans, C. tropicalis, C. parapsilosis – sepsis with muscle pain and weakness Chikungunya fever – morbilliform exanthem of the trunk and limbs with islands of sparing; high fever, headache, photophobia, myalgia, arthralgias J Clin Diagn Res 10:OD05-OD06, 2016; JAMADerm 151:257–258, 2015; Coxsackie virus An Med Interna 25:90–92, 2008 Cysticercosis (Taenia solium) (Cysticercus cellulosae) – undercooked pork; multiple asymptomatic subcutaneous nodules; multiple red painless nodules of legs; abdominal pain, muscle edema and pain; diarrhea; neurocysticercosis JAAD 75:19–30, 2016; JAAD 73:929–944, 2015; JAAD 43:538–540, 2000; JAAD 25:409–414, 1991; NEJM 330:1887, 1994; JAAD 12:304–307, 1985 Cytomegalovirus myositis – severe myalgias, weakness, markedly elevated CPK Dengue fever – Guillain-Barre syndrome Arq Neuropsiquiatr 62:144–146, 2004 Epstein-Barr virus Hepatitis A infection – skin rash and muscle weakness Case Rep Gastrointest Med 2014:286914 Herpes zoster – phrenic nerve palsy, respiratory compromise, C3, C4, and C5 dermatomes Afr Health Sci 19:2347–2350, 2019; acute orbital myositis before V1 zoster Can J Ophthalmol Dec 23, 2019; pseudohernia of abdomen Medicine 98:e15037, 2019 Histoplasmosis (disseminated) in AIDS – facial papules, crusted papules, muscle weakness, pulmonary infiltrates; morbilliform rash with scale BJD 173:797–800, 2015 ICU-acquired weakness and recovery from critical illness NEJM 370:1626–1635, 2014 HIV infection – polymyositis, erythema nodosum Asian Pac J Allergy Immunol 20:175–178, 2002 HTLV-1 rash – tropical spastic paresis, intractable Rare Dis Res 71:61–64, 2018

Rickettsia conorii (Mediterranean spotted fever; Boutonneuse fever); tache noir and non-pruritic morbilliform eruption Cureus 9:e974, 2017 Rocky Mountain spotted fever (Rickettsia Helvetica) J Infect 58:79–82, 2009 Salmonella enteritidis – pyomyositis in HIV disease Br J Rheumatol 34:568–571, 1995 Schistosomiasis Parasitol Res 110:1–18, 2012 Syphilis – transverse myelitis Medicina (Kaunas) 42:401–405, 2006; neurosyphilis in HIV disease Afr Health Sci 10:211–214, 2010 Toxic shock syndrome – group A Streptococcal infection Eur J Pod 161:497–498, 2002 Toxoplasmosis Parasitol Res 110:1–18, 2012 Trench fever (Bartonella quintana) – red macules, 1 cm or less; headache, dizziness, fever lasting 4–8 days, malaise, chills, conjunctivitis, myalgias, arthralgias, severe shin pain, lymphadenopathy, evanescent rash; “culture negative endocarditis” JAAD 82:533–548, 2020; Clinics in Dermatol 28:483–488, 2010 Trichinosis – myalgia, periorbital edema, urticarial and morbilliform exanthems, splinter hemorrhages JAAD 73:929–944, 2015; Clin Exp Dermatol 26:272–273, 2001 Varicella zoster virus myelitis – leg paresis J Pain Palliat Care Pharmacother 24:33–38, 2010; brachial plexopathy J Neurol 256:1343–1345, 2009 West Nile virus Curr Infect Dis Rep Nov 15, 2013 Zika virus – fever, morbilliform (macular and papular exanthem), arthralgia, conjunctivitis, myalgia, headache, retro-orbital pain, edema; Africa, Asia, Yap Island, Micronesia; mosquito vector (Aedes hensilli) JAAD 74:1286–1287, 2016; Clin Inf Dis 61:1445,1485– 1486, 2015; NEJM 360:2536–2543, 2009

INFILTRATIVE DISORDERS Scleromyxedema – proximal muscle weakness Rheum Dis Clin North Amer 39:347–364, 2013; Blood 107:463–466, 2006; Clin Dermatol 24:493–497, 2006; Semin Cut Med Surg 25:100–104, 2006; JAAD 44:273–281, 2001 Self-healing juvenile cutaneous mucinosis – myalgias, swelling of joints with refusal to walk; erythema and edema of the upper and lower eyelids, violaceous periarticular nodules, skin-colored nodules of the neck and abdomen Am J Dermatopathol 34:699–705, 2012; ; AD 145:211–212, 2009; JAAD 55:1036–1043, 2006; JAAD 50:S97–100, 2004; AD 131:459–461, 1995

Influenza – myocarditis, myositis, acute renal failure Netter’s Infectious Diseases, pp. 34–37, 2012

INFLAMMATORY DISORDERS

Leprosy – type 1 reaction demonstrates reappearance of resolved lesions, with erythema, edema, and paresthesias; acute peripheral neuritis, weakness, anesthesia; edema of the hands, feet, arms, and face JAAD 83:17–30, 2020; BJD 158:648–649, 2008; JAAD 57:914–917, 2007

Eosinophilic cellulitis-like lesions associated with eosinophilic myositis AD 133:203–206, 1997; annular plaque with pustules JAAD 51:S71–73, 2004; eosinophilic myositis/perimyositis JAAD 37:385–391, 1997; eosinophilic cellulitis-like lesions associated with eosinophilic myositis – urticaria-like lesions AD 133:203–206, 1997

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Focal myositis – swollen calf J Neurol Sci 170:64–68, 1999 Inclusion body myositis – forearm muscle atrophy (personal observation) Polymyositis – swollen calf J R Soc Med 96:236–237, 2003 Relapsing eosinophilic perimyositis – fever, fatigue, and episodic muscle swelling; erythema over swollen muscles BJD 133:109–114, 1995

METABOLIC DISORDERS Amyloidosis Hum Pathol 29:463–468, 1998 Biotinidase deficiency Cretinism – coarse facial features, lethargy, macroglossia, cold dry skin, livedo, umbilical hernia, poor muscle tone, coarse scalp hair, synophrys, no pubic or axillary hair at puberty Cystinosis – white facial papules; renal failure, ocular, pancreatic, hepatic, muscular, dental, gonadal, and neurologic involvement, hypothyroidism JAMA Derm 152:108–109, 2016 Hereditary LDH M subunit deficiency – annular red rash in summer, resolves in autumn; muscular symptoms; small papules and annular red centrifugal spread AD 122:1420–1424, 1986; hereditary lactate dehydrogenase M subunit deficiency without IL-36 receptor antagonist mutation – pustular psoriasis-like eruption; erythematous skin lesions; psoriasiform dermatitis; annular desquamative plaques; fatigue, myalgia, myoglobinuria, increased creatine kinase BJD 172:1674–1676, 2015; JAAD 27:262–263, 1992; JAAD 24:339–342, 1991 Intravenous drug abuse (serotonin syndrome) – tachycardia, hypothermia; MDMA (Ecstasy or Molly); rhabdomyolysis; Clin Inf Dis 61:1840–1849, 2015 Multiple mitochondrial respiratory chain complex deficiencies – muscle, central nervous system, cardiac, and liver involvement JAMA 312:68–77, 2014 Neutral lipid storage disease (Dorfman-Chanarin syndrome) – autosomal recessive; at birth collodion baby or ichthyosiform erythroderma; thereafter pattern resembles non-bullous ichthyosiform erythroderma; hypohidrosis; ectropion; palmoplantar hyperkeratosis, WBC vacuoles, myopathy, fatty liver, CNS disease, deafness JAAD 17:801–808, 1987; AD 121:1000–1008, 1985 Phosphoglucomutase 1 deficiency – autosomal recessive; disorder of glycosylation with impaired glycoprotein production; liver dysfunction, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, cardiac arrest NEJM 370:533–542, 2014 Post-reperfusion syndrome – massive edema of muscles; may lead to amputation; peripheral cyanosis, livedo reticularis, edema of the foot; myocardial injury, renal failure Int Wound J March 3, 2014; Semin Vasc Surg 22:52–57, 2009; Plast Reconstr Surg 117:1024– 1033, 2006 Scurvy – leg weakness NEJM 379:282–289, 2018; Can Fam Physician 54:1403–1406, 2008 Selenium deficiency – xerosis, alopecia, leukotrichia, leukonychia; pancytopenia, muscle weakness, muscle pain, cardiac arrhythmia, unsteady gait, distal paresthesias JAAD 80:1215–1231, 2019; Nutrition 23:782–787, 2007; Nutrition 12:40–43, 1996

NEOPLASTIC DISORDERS Fibrous hamartoma of infancy – dimpled subcutaneous mass with hypertrichosis; bony remodeling and muscle atrophy Ped Derm 36:677–680, 2019

Lymphoma – granulomatous cutaneous T-cell lymphoma Muscle Nerve 36:860–865, 2007 Merkel cell carcinoma with paraneoplastic Lambert-Eaton myasthenia syndrome; cerebellar degeneration with autonomic neuropathy JAAD 75:541–547, 2016 Pilomatrixoma – multiple pilomatrixomas associated with myotonic dystrophy and familial gastrointestinal polyps Ped Derm 32:97–101, 2015

PARANEOPLASTIC DISORDERS Myasthenia gravis and paraneoplastic pemphigus BJD 172:968– 975, 2015 Paraneoplastic pemphigus BJD 159:986–988, 2008 Scleromyxedema Acta Mycol 38:13–16, 2019; J Neurol 266:2051– 2059, 2019

PRIMARY CUTANEOUS DISEASES Degos’ disease – myalgia, weakness; flat, white papules with erythematous telangiectatic halos NEJM 370:2327–2337, 2014 Palmoplantar keratoderma with amyotrophy Dermatologica 176:251–256, 1988

SYNDROMES Aicardi-Goutieres syndrome – mutation of SAMHD1 Arthritis Care Res (Hoboken) 65:11539–11547, 2013 Brown-Crounse syndrome – 1–2 mm papules, plaques, and nodules, diffuse hypotrichosis resembling alopecia areata, basaloid follicular hamartomas, trichoepitheliomas, myasthenia gravis AD 99:478–493, 1969 Congenital ichthyosis, hypogonadism, small stature, facial dysmorphism, scoliosis, and myogenic dystrophy Ann Genet 42:45–50, 1999 Deafness, vitiligo, and muscle wasting of the hands, feet, and legs Arch Otolaryngol 93:194–197, 1971 Ekbom’s syndrome (myoclonic epilepsy and ragged muscle fibers) (mitochondrial syndrome) – cervical lipomas JAAD 39:819–823, 1998 Familial myopathy with Marfanoid features and multicores Aust N Z J Med 14:495–499, 1984 Fascioscapular muscular dystrophy – poikiloderma AD 107:115– 117, 1973 Frydman syndrome – autosomal recessive; prognathism, syndactyly, short stature, blepharophimosis, weakness of extraocular and frontal muscles, synophrys Clin Genet 41:57–61, 1992 Hereditary fibrosing poikiloderma – poikiloderma of cheeks, alopecia, myopathy with fatty infiltration of muscles, hypohidrosis, lymphedema of the hands and legs, exocrine pancreatic insufficiency, extraocular muscle weakness, with tendon contracture, fibrosis, pulmonary fibrosis, and alopecia; FAM IIIB mutation – mimics Rothmund-Thomson syndrome; mutation in FAMIIIB (POIKTMP) BJD 176:534–536, 2017; Cases of the Year, Pre-AAD Pediatric Dermatology Meeting, 2016 Isaacs’ syndrome (tetrad of stiffness, myokymia, weakness, and pseudomyotonia) – desquamating rash and cold-induced allodynia Cureus 11:e4687, 2019 Kawasaki’s disease J Pediatr 154:592–595, 2009

Myocarditis, Cutaneous Manifestations 657 Kuskokwim syndrome – autosomal recessive, multiple melanocytic nevi, joint contractures, muscle atrophy, decreased corneal reflexes, skeletal abnormalities Curr Prob in Derm VII:143–198, 1995 Marfan’s syndrome with neurogenic muscle atrophy Kurume Med J 38:275–279, 1991 Mulibrey nanism – nevus flammeus, muscle hypotonia, triangular face, thinness JAAD 46:161–183, 2002; Birth Defects 11:3–17, 1975 Myotonic dystrophy – Marfanoid habitus Ophthalmology 86(10):1764–1793, 1979; myotonic dystrophy (Steinert) – multiple pilomatrixomas Ped Derm 23:157–162, 2006; Ped Derm 12:331– 335, 1995 Nakajo-Nishimura syndrome – genetic inflammatory myopathy, fever, skin rash, muscle weakness, atrophy Neuropathol Appl Neurobiol March 6, 2020 Nemaline myopathy – Marfanoid habitus Ophthalmology 86(10):1764–1793, 1979 Nevus spilus syndrome – ipsilateral hyperhidrosis, muscular weakness, dysesthesia Eur J Dermatol 12:133–135, 2002 Pachydermoperiostosis (Touraine-Solente-Gole syndrome) – primary pachydermoperiostosis; autosomal dominant; skin of the face, forehead, scalp folded and thickened; weary expression; cutis verticis gyrata of the scalp; skin of the hands and feet thickened; hyperhidrosis; spade-like hands; clubbing, mental retardation common NEJM 272:923–931, 1956 Primrose syndrome – enlarged calcified ears; distal muscle wasting, diabetes, deafness, basal ganglia calcification Mol Syndromol 9:70–82, 2018 PYCR1-related cutis laxa – hair loss, prominent scalp veins, triangular-­shaped face, microcephaly, short stature, hypermobility of joints, thin atrophic skin, wrinkled skin, muscle weakness, finger contractures Dtsch Arztebl Intl 16:489–496, 2019 Reed syndrome – with myopathy BJD 172:1442–1445, 2015 Wrinkly skin syndrome (possibly same as geroderma osteodysplastica) – autosomal recessive; aged appearance with wrinkled skin on the abdomen and dorsal aspects of the hands and feet, increase palmoplantar creases, prominent venous pattern on the chest, intrauterine growth retardation, mental retardation, microcephaly, hypotonia, musculoskeletal abnormalities Ped Derm 25:66–71, 2008; Ped Derm 23:467–472, 2006; Am J Med Genet 101:213–220, 2001; Ped Derm 16:113–117, 1999

Polyarteritis nodosa J Korean Med Sci 21:591–595, 2006; cutaneous polyarteritis nodosa – fever, muscle weakness and myalgia, and livedo with necrosis (livedo racemosa) NEJM 378:2518–2529, 2018; JAAD 73:1013–1020 2015; BJD 171:201–202, 2014; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014 Severe disabling myalgia and vasculitic rash Case Rep Rheumatol April 7, 2019 Volkmann’s ischemic contracture (neonatal compartment syndrome) – of the forearm – asymmetric, well-demarcated, stellate ulcers of arms with neuromuscular defects; in newborn; serpiginous border; muscle necrosis and nerve palsy due to increased intracompartmental pressure from amniotic band, oligohydramnios or abnormal fetal position; begins as large bulla Ped Derm 37:207–208, 2020; JAMA Derm 150:978–980, 2014; Ped Derm 25:352–354, 2008   Differential diagnosis includes:    Aplasia cutis congenita   Epidermolysis bullosa   Necrotizing fasciitis    Subcutaneous fat necrosis   Protein C or S deficiency with disseminated intravascular coagulation    Neonatal ecthyma gangrenosum from bacterial infection   Aspergillosis    Varicella zoster virus infection

MYOCARDITIS, CUTANEOUS MANIFESTATIONS  UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION Adult-onset Still’s disease Korean Circ J 44:437–440, 2014; Rev Med Interne 35:827–830, 2014; Int J Rheum Dis 12:272–274, 2009 Bullous pemphigoid Dermatology 204:161–162, 2002

TOXINS

Graft vs. host disease, acute Bone Marrow Transplantation 27:107–109, 2001

Eosinophilia myalgia syndrome – l-tryptophan Arthritis Rheum 61:1305–1311, 2009

Lupus erythematosus, neonatal Rev Med Interne 36:159–166, 2015; systemic lupus erythematosus Lupus 23:1426–1429, 2014

Mercury poisoning Eur J Pediatr 2010. Oct 6

Polymyositis – with giant cell myocarditis and rash Lung 40;40–45, 2011

Octopus ingestion toxicity – diffuse erythema Rev Inst Med Trop Sao Paolo 49:59–61, 2007

VASCULAR LESIONS Eosinophilic granulomatosis with polyangiitis – post-exercise myositis J Clin Neurosci 16:1232–1233, 2009 Cutaneous polyarteritis nodosa – atrophie blanche lesions, acrocyanosis, Raynaud’s phenomenon, peripheral gangrene, red plaques and peripheral nodules, myalgias; macular lymphocytic arteritis – red or hyperpigmented reticulated patches of legs JAAD 73:1013–1020, 2015 Giant cell arteritis and polymyalgia rheumatica NEJM 371:50–57, 2014

DRUG REACTIONS Drug eruption with exanthema and systemic symptoms (DRESS) JAAD 66:229–236, 2012; NEJM 357:2167–2178, 2007; Arch Pathol Lab Med 115:764–769, 1991; fever, eosinophilia, death; multiple drugs; minocycline; giant cell myocarditis, eosinophilic myocarditis Cutis 93:107–110, 2014 Hypersensitivity myocarditis due to medications (rash and peripheral eosinophilia):  Allopurinol Ann Acad Med Singapore 31:231–233, 2002  Amoxicillin Korean J Int Med 29:236–240, 2014  Carbamazepine Cent Eur J Immunol 44:102–105, 2019

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 Dapsone Neth J Med 74:89–92, 2016; Ann Acad Med Singapore 35:833–836, 2006  Flurbiprofen Am J Emerg Med 27:132, 2009   Gefitinib (Iressa) Arch Path Lab Med 129:1044–1046, 2005  Isoniazid Intern Med 54:102–105, 2019  Lenalidomide Am Pharmacother 44:1840–1843, 2010  Minocycline Cutis 93:107–110, 2014; JAAD 62:315–318, 2010  Phenobarbital Jpn Circ J 62:132–135, 1998  Salazosulfapyridine Drug Disease Ther 13:232–238, 2019

INFECTIONS AND INFESTATIONS Borrelia recurrentis – louse-borne relapsing fever Epidemiol Infect 147:e106, 2019 Chagas’ disease (Trypanosoma cruzi) – reactivation in a heart transplant recipient with fever, myocarditis, and rash Curr Opin Inf Dis 25:450–457, 2012; in a renal transplant recipient Transpl Inf Dis 14:391–397, 2012 Chikungunya fever (Chikungunya virus) – Africa, Middle East, Europe, India, Southeast Asia; fever, arthralgias, morbilliform eruption; polyarthritis and tenosynovitis; hepatitis, myocarditis, hemorrhage, meningitis, encephalitis; palpebral edema; purpuric butterfly eruption of the face; necrosis of the skin of the nose Inf Dis Clin NA 33:1003–1025, 2019; Clin Inf Dis 62:78–81, 2016; Med Trop (Mars)72:88–93, 2012 Coxsackie A4 hand-foot-and-mouth disease Front Microbiol May 7, 2019 Coxsackie A6, A16, and A10 – hand,-foot-and-mouth disease and myocarditis Case Rep Dermatol Aug 7, 2013 Coxsackie A6 with atypical hand,-foot-and-mouth disease with vesiculobullous exanthema of trunk, extremities, and perioral areas Case Rep Dermatol Aug 7, 2013 Coxsackie B4 and B5 infection Dengue fever Am J Trop Med 101:448–450, 2019; acute myocarditis in dengue hemorrhagic fever Int J Infect Dis 14:e919–922, 2010 Diphtheria – bull neck due to lymphadenopathy, myocarditis, peripheral neuropathy, pharyngitis with membranes NEJM 381:1267, 2019; Netter’s Infectious Diseases, pp. 5–10, 2012; Corynebacterium diphtheriae Indian J Cardiol 98:351–354, 2005 Enterovirus 71 J Pathol 235:217228, 2015 Erysipelas – Group A streptococcal erysipelas and acute myocarditis Can J Card 29:1138, 2013 Hepatitis A Case Rep Med Sept 13, 2018 Influenza – myocarditis, myositis, acute renal failure Netter’s Infectious Diseases, pp. 34–37, 2012 Lyme disease Clin Cardiol 41:1611–1616, 2018 Mayaro virus – morbilliform eruption Emerg Microbiol Infect 7:163, 2018 Meningococcemia Pan Afr Med J 29:149, 2018; Int Med Case Rep J 6:33–36, 2013 Parvovirus B19 Rev Med Interne 35:289–296, 2014; Diagn Pathol 3:21, 2008; Human Pathol 32:342–345, 2001 Q fever (Coxiella burnetii) – pneumonia, high fever, headache, hepatitis, myocarditis NEJM 376:869–874, 2017 Rat bite fever – hemorrhagic vesicles of the hands and feet with petechiae JAMADerm 153:707–708, 2017; Clin Microbiol Rev 20:13–22, 2007 Rheumatic fever – Group A streptococcus; erythema migrans, subcutaneous nodules, carditis Circulation 121:946–947, 2010

Rickettsia conorii BMC Infect Dis 18:705, 2018 Salmonella Typhi (typhoid fever with rose spots) Dtsch Med Wochenschr 133:1493–1496, 2008 Scrub typhus Oman Med J 34:254–256, 2019; Am J Trop Med Hyg 87:1099–1104, 2012 Toxocara canis in humans – eosinophilia, fever, hepatomegaly, hyperglobulinemia, lung and central nervous system lesions, myocarditis, and skin rash Med Parazitol (Musk) April-June 3–6, 2011 Trypanosomiasis (East African trypanosomiasis) – non-painful trypanosomal chancre with central necrosis and peripheral erythema BMC Inf Dis Feb 27, 2014 Varicella zoster virus Pediatr Cardiol 31:703–706, 2010 Zika virus, acute infection – transient myocarditis Clin Inf Dis 64:678–679, 2017

INFLAMMATORY DISORDERS Orbital myositis and giant cell myocarditis JAAD 35:310–312, 1996; Ophthalmology 101:950–954, 1994 Ulcerative colitis Intern Med 58:1111–1118, 2019; Tex Heart Inst J 44:219–222, 2017

PRIMARY CUTANEOUS DISEASES Febrile ulceronecrotic Mucha-Habermann disease J R Soc Med 82:500–501, 1989 Pyoderma fistulans sinifica J Plast Recon Surg 64:e12–16, 2011

SYNDROMES Epidermolysis bullosa simplex with cardiomyopathy – loss of dermatoglyphics, hypohidrosis; mutation in KLHL24 BJD 179:1181– 1183, 2018 Hypereosinophilic syndrome – intractable pruritus, pulmonary infiltrates, eosinophilic gastroenteritis, endomyocardial fibrosis, thromboembolism NEJM 380:1336–1346, 2019; AD 132:535–541, 1996; Med Clin (Barc)106:304–306, 1996 Kawasaki’s disease (mucocutaneous lymph node syndrome) Cardiovasc Pathol 11:318–321, 2002; in adult Cureus 11:e5529, 2019

TOXINS Eosinophilia myalgia syndrome – associated with L-tryptophan ingestion Ann Int Med 113:124–134, 1990

TRAUMA Radiation recall J Cardiovasc Magn Reson April 22, 2015

VASCULAR LESIONS Eosinophilic granulomatosis with polyangiitis – eosinophilic myocarditis BMJ Case Rep Aug 15, 2019 Henoch-Schonlein purpura G Ital Cardiol 14:622–625, 2013 Takayasu’s arteritis Int J Cardiol 54:S149–154, 1996

NAIL ABNORMALITIES

Congenital onychodysplasia of the index finger Genetic Skin Disorders, Second Edition, 2010, pp.244 Congenital paramedian canaliform dystrophy – personal observation

BJD 173:922–979, 2015

 UTOIMMUNE DISEASES AND DISORDERS A OF IMMUNE DYSREGULATION

DRUG REACTIONS Acitretin – trachyonychia Cureus 12:e6703, 2020

APECED syndrome BJD 178:335–349, 2018 Chronic mucocutaneous candidiasis – crusted plaques, cicatricial alopecia, leukoplakia, dystrophic nails Ped Derm 34:609–611, 2017 Dectin-1 deficiency – candidiasis of nails BJD 178:335–349, 2018

Actinomycin D – brown nails Amiodarone pigmentation – personal observation Anthralin – brown or orange nails Antimalarials – blue nails

Epidermolysis bullosa acquisita – nail dystrophy BJD 171:1022– 1030, 2014

AZT (zidovudine) – blue lunulae, blue nails JAAD 46:284–293, 2002 Bleomycin – blue nails; brown nails

Gain of function STAT1 mutations – chronic mucocutaneous candidiasis; onychodystrophy, generalized dermatophytosis; disseminated coccidioidomycosis, histoplasmosis, sinopulmonary infections, herpes simplex infections; endocrine, dental, gastrointestinal disease; diabetes mellitus, hypothyroidism, autoimmune hepatitis, cerebral aneurysms, oral and esophageal squamous cell carcinomas; increased levels of interferon results in decreased IL-17A and IL-22 JAAD 73:255–264, 2015

Chloroquine – black nail beds AD 88:419–426, 1963 Combination chemotherapy – cyclophosphamide, vincristine, doxorubicin, dacarbazine; blue lunulae JAAD 32:296, 1995; cisplatin, ifosfamide, temozolomide, and vincristine – blue lunulae J Drugs Dermatol 12:223–226, 2013 Cyclophosphamide – black nails Daunorubicin – black nails

Graft vs host disease – pterygium unguis inversum J Eur Acad DV 33:637–642, 2019

Docetaxel/paclitaxel – nail changes JAAD 71:203–214, 2014

Hyper IgE syndrome – candida of nails; retained primary teeth leading to double rows of teeth; lack of eruption of secondary teeth, delayed resorption of roots of primary teeth BJD 178:335–349, 2018; JAAD 60:289–298, 2009; JAAD 54:855–865, 2006

Pegylated liposomal doxorubicin – red hands and feet (acral erythrodysesthesia); follicular exanthem, intertrigo, alopecia, nail changes, stomatitis BJD 176:507–509, 2017

Lupus erythematosus, systemic – pterygium; pterygium unguis inversum J Drugs Dermatol 12:344–346, 2013; melanonychia JAAD 47:S187–188, 2002; pincer nails Lupus 26:1562–1563, 2017

Gefitinib – nail hyperpigmentation JAAD 77:902–910, 2017

Doxycycline – brown nails Gold salts – black nails Ibrutinib – diarrhea, brittle fingernails and toenails with onychorrhexis JAMADerm 152:698–701, 2016

Rheumatoid arthritis – red lunulae Sclerederma – trachyonychia, scleronychia, thickened nails, brachyonychia, parrot beaking, pterygium unguis inversum, splinter hemorrhages JAAD 76:1115–1123, 2017

Imatinib – nail hyperpigmentation JAAD 77:902–910, 2017 Ketoconazole – brown nails Mepacrine – blue nails BJD 130:794–795, 1994

STAT1 gain of function mutation – most common cause of chronic mucocutaneous candidiasis; demodicidosis with facial papulopustular eruptions, blepharitis, chalazion, dermatitis of the neck, nail dystrophy, congenital candidiasis Ped Derm 37:159–161, 2020

Minocycline – blue nails Nitrogen mustard – brown nails

STING-associated vasculopathy with onset in infancy (SAVI) (type 1 interferonopathy) – red plaques of face and hands; chilblain-like lesions; atrophic plaques of hands, telangiectasias of cheeks, nose, chin, lips, acral violaceous plaques and acral cyanosis (livedo reticularis of feet, cheeks, and knees), distal ulcerative lesions with infarcts (necrosis of cheeks and ears), gangrene of fingers or toes with ainhum, nasal septal perforation, nail dystrophy; small for gestational age; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis with ground glass and reticulate opacities; gain of function mutation in TMEM173 (stimulator of interferon genes); mimics granulomatosis with polyangiitis Ped Derm 33:602–614, 2016; JAMADerm 151:872–877, 2015; NEJM 371:507–518, 2014 T-cell immunodeficiency, congenital alopecia, and nail dystrophy Clin in Dermatol 23:47–55, 2005

Penicillin allergy – onychomadesis (shedding of nail) Phenolphthalein (X-Lax) – blue lunulae Psoralen – brown nails Sulfonamides – brown nails Tetracycline – teeth; brown nails Zidovudine – black nails

EXOGENOUS AGENTS Argyria - blue lunulae and blue nails Coal tar – black nails Copper stains, swimming pool – personal observation Ebony workers – black nails Formaldehyde nail hardeners – blue discoloration of nails; gray nails

CONGENITAL DISORDERS Congenital malalignment of the great toenail – thickened nails J Cut Med Surg 13:276–279, 2009 Congenital malalignment of the great toenails Dermatol Surg 45:1211–1213, 2019; Clin Exp Dermatol 8:619–623, 1983; Clin Exp Dermatol 4:309–313, 1979

Gentian violet – purple nails; gray nails Iodine – brown nails Mercury-containing cosmetics – black nails Nail polish, nail hardeners – brown or orange hyperpigmentation Photographic developing (methyl or p-methyl aminophenyl sulfate hydroquinone) – black nails 659

660 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Shoe polish – black nails

INFLAMMATORY DISORDERS

Silver nitrate – gray or black nails

Erythema multiforme – atrophic nails

Synthetic opioid MT-45 – hair depigmentation, hair loss, Mees’ lines BJD 176:1021–1027, 2017 Wine – black nails

INFECTIONS AND INFESTATIONS Aspergillus flavus – deep superficial white onychomycosis JAAD 66:494–502, 2012

Sarcoidosis – pterygium, nail dystrophy Skeletal Radiol 45:717– 721, 2016; Clin Exp Dermatol 38:119–124, 2003 Stevens-Johnson syndrome – hypertrophic nails; atrophic nails Dermatol Clin 33:207–241, 2015; Beau’s lines or transverse lines; onychomadesis or shedding; anonychia AD 113:970, 1977 Toxic epidermal necrolysis Pediatr 109:74–78, 2002

Aspergillus niger – proximal subungual white onychomycosis JAAD 66:494–502, 2012

METABOLIC DISORDERS

Bacterial subungual infections – Pseudomonas aeruginosa, Klebsiella spp., Proteus spp. – longitudinal melanonychia Dermatol Surg 27:580–584, 2001

Acrodermatitis enteropathica – shedding and onychomadesis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.462–463

Candidiasis – of skin; of nails in congenital candidiasis Textbook of Neonatal Dermatology, p.513, 2001

Beau’s lines

Chronic mucocutaneous candidiasis Ped Inf Dis J 20:197–206, 2001; JAAD 31(PT 2)514–517, 1994 Dermatophytoma – linear white or yellow nail band JAAD 66:1014– 1016; J Drugs Dermatol 14:524–526, 2015; JAAD 66:1014–1016, 2012; BJD 138:189–190, 1998

Acromegaly – onychauxis (hypertrophy of nail) Congenital erythropoietic porphyria Genetic Skin Disorders, Second Edition, 2010,pp.608–612 Congestive heart failure – red nails, lunulae Hemochromatosis – thin nails Genetic Skin Disorders, Second Edition, 2010,pp.308–311

Epidermophyton floccosum – green nails

Hemoglobin M disease – blue lunulae

Fusarium – superficial white onychomycosis JAAD 66:494–502, 2012; JAAD 65:1219–1227, 2011

Hyperparathyroidism, acquired racket nails J Eur Acad DV 28:257–259, 2014

Lymphogranuloma venereum – red nails, red lunulae

Koilonychia (spoon shaped nails) – iron deficiency anemia (Plummer-Vinson syndrome); repeated occupational trauma NEJM 379:e13 2018; J Eur Acad DV 30:1985–1992, 2016

Onychomycosis – hypertrophic nail plates JAAD 80:835–851, 2019; JAMA 316:1915–1916, 2016; AD 147:1277–1282, 2011; distal subungual onychomycosis JAAD 73:62–69, 2015; onychomycosis in CARD9 deficiency; autosomal recessive JAMADerm 151:192– 194, 2015; Dermatol Clin 33:175–183, 2015; superficial white onychomycosis – zebra stripes JAAD 57:879–882, 2007 Pseudomonas – green nails Scabies – nail dystrophy Ped Derm 35:829–830, 2018 Scopulariopsis brevicaulis – opaque thick nails JAAD 66:494–502, 2012 Syphilis – brown nails; secondary – “onychia sicca syphilitica” – well demarcated purplish opaque rough vertically ridged plaque-like lesions of proximal portions of fingernails SAGE Open Med Case Rep March 28, 2018; BJD 23:368–377, 1911

Lindsay’s nails – half and half nail of chronic renal failure Melanonychia striata in regression – “dots and lines” Ped Derm 34:e321–323, 2017 Muehrcke’s lines – zebra stripes; hypoalbuminemia, paired transverse hypopigmented bands BMJ 1:1327–1328, 1956; AD 143:815–816, 2007 Necrolytic migratory erythema (glucagonoma syndrome) – brittle nails JAMADerm 155:1180, 2019; Int J Dermatol 49:24–29, 2010; J Eur Acad Dermatol 18:591–595, 2004 Neapolitan nails – age related changes of nails in otherwise healthy individuals similar to Terry’s, Lindsay’s, or Muehrcke’s nails Ochronosis – blue-gray nails

Trichophyton rubrum – proximal white onychomycosis JAAD 65:1219–1227, 2011

Pernicious anemia, congenital – blue nails

Warts – wart over nail matrix – longitudinal nail groove

Porphyria cutanea tarda – photoonycholysis; discoloration of nails and onycholysis Photodermatol Photoimmunol Photomed 18:202– 207, 2002; Genetic Skin Disorders, Second Edition, 2010,pp.618–620

INFILTRATIVE DISORDERS Amyloidosis – primary systemic amyloidosis – longitudinal ridging, onychorrhexis, zebra stripes; linear striations of nails JAMADerm 152:1395–1396, 2016; nail dystrophy JAAD 54:712–714, 2006; trachyonychia JAMADerm 150:1357–1358, 2014; brittleness, longitudinal ridging, subungual thickening, onycholysis, anonychia Dermatology 228:97–102, 2014; Dermatologica 183:44–46, 1991; primary systemic amyloidosis – atrophic nail dystrophy JAAD 54:712–714, 2006 Langerhans cell histiocytosis – pterygium of the nails JAAD 78:1035–1044, 2018; purpuric nail striae with paronychia Ped Derm 37:182–183, 2020; onycholysis and subungual hyperkeratosis Ped Derm 34:732–734, 2017

Polycythemia vera – red lunulae

Pregnancy – brown nails Renal disease – hypopigmented hair; transverse white nail bands; half and half nails (Lindsay’s nails) Selenium deficiency – xerosis, alopecia, leukotrichia, leukonychia; pancytopenia, muscle weakness, muscle pain, cardiac arrhythmia, unsteady gait, distal paresthesias JAAD 80:1215–1231, 2019; Nutrition 23:782–787, 2007; Nutrition 12:40–43, 1996 Terry’s nails – personal observation Thyroid disease – white lunulae

Nail Abnormalities

NEOPLASMS Atrial myxoma – emboli with nail degloving JAAD 58:232–237, 2008 Atypical melanocytic hyperplasia – longitudinal melanonychia Dermatol Surg 27:580–584, 2001 Bowen’s disease – linear longitudinal melanonychia JAAD 39: 490–493, 1998; periungual erythematous squamous or eroded plaque; in lateral groove; a recalcitrant hyperkeratotic or papillomatous lesion Chondroma – subungual soft tissue chondroma Ped Derm 32:132–134, 2015 Chondrosarcoma of distal phalanx Acta DV 95:1026–1027, 2015 Digital myxoid cyst – linear nail groove Enchondromas – red nails Fibrokeratoma – longitudinal linear groove Dermatol Clin 33:243– 255, 2015 Glomus tumor – longitudinal erythronychia JAMADerm 152:1271– 1272, 2016 Leiomyoma – subungual leiomyoma; erythronychia and nail dystrophy J Drugs Dermatol 18:465–467, 2019 Lentigo simplex – longitudinal melanonychia Dermatol Surg 27:580–584, 2001 Lymphoma – Sezary syndrome; onychauxis, anonychia, distal notching, onychoschizia J Cut Med Surg 23:380–387, 2019; JAAD 79:972–973, 2018 Melanoma of nail apparatus JAAD 73:213–220, 2015; subungual in situ melanoma – totally black nail BJD 174:935, 2016; melanoma in situ J Drugs Dermatol 16:268–270, 2017; subungual amelanotic melanoma – ulcerated nodule of nail bed JAMA 319:713–714, 2018; hemorrhagic nail bed with rim of hyperpigmentation NEJM 381:1853, 2019; amelanotic subungual melanoma; linear fissure of nail AD 148:947–952, 2012 Mucoepithelial dysplasia Genetic Skin Disorders, Second Edition, 2010,pp.698–700 Myxoid cyst (over nail matrix) – longitudinal nail groove often with Heberden’s nodes Onychomatricoma – parallel white and yellow nail bands with thickening of the nail plate; multiple subungual perforations JAAD 76:S19–21, 2017; localized yellow thickening with transverse overcurvature and splinter hemorrhages BJD 173:1305–1307, 2015; Dermatol Clin 33:197–205, 2015; hyperkeratotic nail with black dots AD 147:1117–1118, 2011; severe subungual hyperkeratosis Society of Pediatric Dermatology Annual Meeting, July, 2015; banded or diffuse thickening of nail with yellowish discoloration, splinter hemorrhages, and transverse overcurvature (thick yellow nail) Cutis 96:121–124, 2015;onycholysis with linear yellow band JAAD 70:395–397, 2014   Differential diagnosis of onychomatricoma    Acquired digital fibrokeratoma of nail matrix   Aggressive angiomyxoma   Angiokeratoma    Basal cell carcinoma of nail unit   Bowen’s disease   Nail fibroma   Glomus tumor    Juvenile xanthogranuloma of proximal nail fold    Langerhans cell histiocytosis   Longitudinal melanonychia    Malignant proliferating onycholemmal cyst   Melanocytic nevus   Nail psoriasis   Neurofibroma

661

  Onychodystrophy    Onychogenic Bowen’s disease   Onychogryphosis   Onycholemmal horn   Onychomycosis   Pachyonychia congenital    Periungual and subungual warts   Pyogenic granuloma   Longitudinal melanonychia    Nail bed fibrosarcoma    Squamous cell carcinoma   Subungual exostosis   Subungual keratoacanthoma   Subungual melanoma   Subungual metastasis   Subungual osteochondroma   Subungual porocarcinoma    Subungual eccrine syringofibroadenoma    Subungual squamous cell carcinoma    Superficial acral fibromyxoma    Verruca vulgaris    Yellow nail syndrome Onychopapilloma – V-shaped distal split of nail, longitudinal erythronychia, longitudinal leukonychia, onycholysis, longitudinal melanonychia, splinter hemorrhages, distal subungual hyperkeratotic mass JAAD 74:521–526, 2016; JAAD 63:541–542, 2010; linear red streak with distal central fissure Dermatol Clin 33:197–205, 2015; onychopapilloma of nailbed and Bowen’s disease – longitudinal erythronychia BJD 143:132–135, 2000; longitudinal leukonychia JAAD 63:541–542, 2010; Osteochondroma – subungual osteochondroma; linear longitudinal nail ridge Ped Derm 11:39–41, 1994 Porokeratosis, linear – nail dystrophy J Dermatol 43:286–287, 2016 Squamous cell carcinoma – HPV and squamous cell carcinoma JAAD 81:1358–1370, 2019; dystrophic thumb nail NEJM 373:2357, 2015 Subungual elastoma Dermatol Online J Sept 15, 2017 Subungual exostosis – hyperkeratotic subungual papule of fingertip Cutis 98:128–129, 2016 Subungual onycholemmal cyst – pressure-induced onycholysis overlying blue discoloration Cutis 98:107–110, 2016

PARANEOPLASTIC DISORDERS Glucagonoma syndrome – brittle crumbling nails; periorbital and perioral erythema; alpha cell tumor in the tail of the pancreas; 50% of cases have metastasized by the time of diagnosis; skin rash, angular stomatitis, cheilosis, beefy red glossitis, blepharitis, conjunctivitis, alopecia; rarely, associated with MEN I or IIA syndromes BJD 174:1092–1095, 2016; JAMADerm 345–347, 2016; JAAD 54:745–762, 2006; JAAD 12:1032–1039, 1985; Int J Derm 43:12–18, 2004; AD 133:909, 912, 1997; JAAD 12:1032– 1039, 1985; Ann Int Med 91:213–215, 1979; AD 45:1069–1080, 1942

PRIMARY CUTANEOUS DISEASES Acrodermatitis continua JAMADerm 153:336–337, 2017; JAMADerm 153:331–332, 2017 Acrokeratosis verruciformis – thin friable nails Genetic Skin Disorders, Second Edition, 2010,pp.54–57 Alopecia areata – red lunulae

662 THE

CLINICIAN’S

GUIDE

TO

DERMATOLOGIC

DIFFERENTIAL

Alpha6-beta4 epidermolysis bullosa – onychogryphosis; yellowbrown discoloration of teeth with enamel defects BJD 169:115–124, 2013; with alopecia totalis BMJ Case Rep Nov 8, 2017 Anonychia – autosomal recessive congenital anonychia – mutation in RSPO4 BJD 173:922–979, 2015; Ped Derm 30:139–141, 2013; congenital totalis Int J Dermatol 41:397–399, 2002 Anonychia of the thumbnails Genetic Skin Disorders, Second Edition, 2010, pp.244–245 Anonychia with flexural pigmentation Genetic Skin Disorders, Second Edition, 2010, pp.244 Autosomal recessive nail dysplasia – mutation in FZD6 encoding Wnt receptor frizzled 6 BJD 178:556–558, 2018; BJD 168:422–425, 2013; BJD 166:1088–1094, 2012 Blue lunulae  Amorolfine   Antimalarials – quinacrine, chloroquine, camoquine  Argyria   AZT infection   Bichloride of mercury (topical)  Combination chemotherapy – cyclophosphamide, vinblastine, vincristine, doxorubicin, dacarbazine, 5-fluorouracil, cyclophosphamide, dactinomycin, bleomycin, busulfan   Cupric acid   Cyanotic disease  Enchondromas   Galvanizers (silver or cyanide)   Glomus tumor  Hemochromatosis   Hemoglobin M disease   Hereditary acrolabial telangiectasias   HIV infection  Minocycline  Ochronosis   Oxalic acid (in radiators)   Phenolphthalein purgative   Pseudomonas paronychia  PUVA  Quinacrine  Thallium  Zidovudine Atrophic nails, congenital Brachydactyly type B1 Clin in Dermatol 23:47–55, 2005 Brittle nails Dermatol Clin 33:175–183, 2015 Claw-shaped nails – onychauxis, hyponychia, onycholysis BJD 173:922–979, 2015 Darier’s disease – red-white streaks; distal notching; thickening SKINmed 13:313–315, 2015; Dermatol Clin 33:197–205, 2015; Clin in Dermatol 23:47–55, 2005; red lunulae; Darier’s disease – onychomadesis (shedding of nail); linear red, white, and pigmented streaks of nails JAAD 27:40–50, 1992 Epidermolysis bullosa – onychomadesis (shedding of nail) Epidermolysis bullosa, all types Epidermolysis bullosa – autosomal dominant epidermolysis bullosa – acral blisters of palms and soles and wrists; nail thickening progresses to anonychia; mutation in ITGB4 JAMADerm 152:558– 562, 2016 Epidermolysis bullosa pruriginosa – anonychia BJD 172:778–781, 2015 Erythronychia J Drugs Dermatol 18:465–467, 2019; SKINmed 9:327–329, 2011; Am J Clin Dermatol 12:217–231, 2011; JAAD 37:74–79, 2011; J Eur Acad Dermatol Venereol 15:85–86, 2001; longitudinal erythronychia BJD 155:219–221, 2006   Acantholytic dyskeratotic epidermal nevus

DIAGNOSIS,

VOLUME

1

  Acantholytic epidermolysis bullosa   Acrokeratosis verruciformis of Hopf  Amyloid   Darier’s disease   Glomus tumor   Graft vs. host disease  Hemiplegia  Idiopathic  Leiomyoma   Lichen planus   Melanoma, amelanotic  Onychopapilloma   Post-surgical scar   Pseudo-bulbar syndrome   Squamous cell carcinoma  Verruca   Warty dyskeratoma Familial dystrophic shedding of the nails Genetic Skin Disorders, Second Edition, 2010,pp.236–238; Cutis 25:622–625, 1980; BJD 88:497–498, 1973; BJD 39:297, 1927 Hereditary palmoplantar keratoderma with deafness Genetic Skin Disorders, Second Edition, 2010,pp.58–60 Hoof nail deformity BJD 169:946–948, 2013 Ichthyosis, gastric hyperplasia, subungual hyperkeratosis, immunologic dysfunction; TTC7A mutations BJD 175:1061, 2016 Ichthyosis en confetti – large lunulae with elongated nails JAMADerm 151:64–69, 2015 Isolated congenital nail dysplasia – autosomal dominant Clin in Dermatol 23:47–55, 2005 Junctional epidermolysis bullosa of late onset (skin fragility in childhood) – speckled hyperpigmentation of elbows; hemorrhagic bullae, teeth and nail abnormalities, oral blisters, disappearance of dermatoglyphics, palmoplantar keratoderma, small vesicles, atrophy of skin of hands BJD 169:714–716, 2013 Keratosis follicularis spinulosa decalvans – elevated cuticles Genetic Skin Disorders, Second Edition, 2010,pp.104–107 Keratosis punctata palmaris et plantaris – onychomadesis (shedding of nail) Leukonychia BJD 173:922–979, 2015; AD 90:392–399, 1964 Leukonychia striata Lichen planus – pterygium JAAD 79:789–804, 2018; atrophy of nail plate; including hemorrhagic nails in bullous lichen planus Ped Derm 34:193–194, 2017; JAMADerm 151:674–675, 2015; onychomadesis (shedding of nail) Lichen striatus – linear nail striations Ped Derm 36:859–863, 2019; subungual hyperkeratosis Ped Derm 33:95–96, 2016; Int J Dermatol 54:1255–1260, 2015 Linear nail bands JAAD 34:943–953, 1996  Black    Longitudinal melanonychia striata  Brown   Antineoplastic agents   Cyclophosphamide   Doxorubicin   Hydroxyurea    Subungual keratosis of nail bed BJD 140:730–733, 1999   Antiviral agents   Zidovudine   Red (longitudinal erythronychia) AD 140:1253–1257, 2004   Cirsoid aneurysm   Darier’s disease   Lichen planus   Glomus tumor

Nail Abnormalities   Onychopapilloma    Squamous cell carcinoma, in situ    Ionizing radiation-induced keratosis  White   Darier’s disease  Yellow   Onychomatricoma – longitudinal bands of yellow thickening of nail plate with transverse overcurvature and splinter hemorrhages; funnel-shaped nail AD 145:1461–1462, 2009; BJD 126:510–515, 1992 Longitudinal melanonychia J Dermatol 46:e89–90, 2019 Median canaliform dystrophy of the nails Dermatol Clin 33:243–255, 2015; Hautarzt 25:629, 1974; Dermat Atschr 51:416–419, 1928; familial Cutis 75:161–165, 2005; following cryosurgery of warts on proximal nail folds Ped Derm 34:726–727, 2017 Nagashima type palmoplantar keratoderma – autosomal recessive; transgradient; acral erythema of palms and soles; hyperkeratosis of elbows and knees and ears; toenail dystrophy; mutation in SERPINB7 BJD 171:847–853, 2014; AD 144:375–379, 2008 Onychogryphosis – acquired; inherited forms – autosomal dominant, congenital forms SKINMed 13:355–359, 2015; Onycholysis BJD 173:922–979, 2015; Dermatol Clin 33:175–183, 2015 Onychomadesis Dermatol Clin 33:243–255, 2015; BJD 172:592– 596, 2015; AD 148:769–770, 2012   Anti-epileptic medications   Cancer chemotherapy   Hand, foot, and mouth disease  Idiopathic   Major medical illness   Pemphigus vulgaris Palmoplantar pustulosis – subungual postulation, nail destruction Int J Dermatol 56:e28–29, 2017; BJD 134:1079, 1082, 1996 Periodic nail shedding – thin or atrophic nails

663

Universal melanosis – thin nails Genetic Skin Disorders, Second Edition, 2010,pp.342–345 Vitiligo – longitudinal ridging, leukonychia, absent lunula, onycholysis, nail bed pallor, onychomadesis, splinter hemorrhages, nail plate thinning An Bras Dermatol 91:442–445, 2016 Vohwinkel’s palmoplantar keratoderma Genetic Skin Disorders, Second Edition, 2010,pp.77–79

PSYCHOCUTANEOUS DISEASES Onychotillomania – total melanonychia; nail dystrophy Am J Clin Dermatol 18:763–770, 2017; JAAD 75:1245–1250, 2016

SYNDROMES Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) – ectrodactyly or syndactyly, freckling and dry skin, dysplastic nails, superficial blisters and desquamation of hands and feet; lacrimal duct atresia, primary hypodontia, conical teeth, and early loss of permanent teeth; small ears hooked nose, sparse thin blond hair, frontal alopecia, hypohidrosis, lacrimal duct atresia, hypoplastic breasts and nipples, urinary tract anomalies; mutation in TP63 gene (encodes transcription factor p63); p63 mutations also responsible for EEC, AEC, limb mammary, and Rapp-Hodgkin syndromes Ped Derm 33:e322–326, 2016; BJD 172:276–278, 2015; Ped Derm 27:643–645, 2010; Hum Mol Genet 11:799–804, 2002; Am J Med Genet 45:642–648, 1993 Activated STING in Vascular and Pulmonary syndrome – autoinflammatory disease; butterfly telangiectatic facies; acral violaceous psoriasiform, papulosquamous, and atrophic vasculitis of hands; nodules of face, nose, and ears; fingertip ulcers with necrosis; nail dystrophy; nasal septal perforation; interstitial lung disease with fibrosis; polyarthritis; myositis NEJM 371:507–518, 2014

Phylloid hypermelanosis – cicatricial alopecia, onychodystrophy, deafness, malformed ear, mental retardation, umbilicated nipples JAAD 19:1037–1044, 1988; Rev Neurol (Paris)95:48–54, 1956

Ankyloblepharon-ectodermal defects-clefting (AEC) syndrome – autosomal dominant; flat face, prominent nose, periorbital wrinkling, hypodontia, sparse hair, alopecia, sparse eyebrows and eyelashes; nail dystrophy; mutation in p63 BJD 166:134–144, 2012

Pincer nails Clin Orthoped Surg 10:285–288, 2018

Anonychia-lymphedema syndrome BMJ Case Rep Nov 8, 2017

Pitting Int J Dermatol 56:3–17, 2017

ANOTHER syndrome – alopecia, nail dystrophy, ophthalmic complications, thyroid dysfunction, hypohidrosis, ephelides and enteropathy, respiratory tract infections Clin Genet 35:237–242, 1989; J Pediatr 108:109–111, 1986

Pityriasis rubra pilaris Genetic Skin Disorders, Second Edition, 2010,pp.46–49 Proximal nail fold pterygium – longitudinal nail groove Psoriasis Ped Derm 34:58–63, 2017; Dermatol Clin 33:175–183, 2015 Punctate palmoplantar keratoderma Genetic Skin Disorders, Second Edition, 2010,pp.68–71 Pure hair and nail ectodermal dysplasia (PHNED) BMC Med Gen April 12, 2017 Pterygium unguis inversum Dermatol Clin 33:257–263, 2015 Normal racial linear brown pigmented bands of nails Racket nails – personal observation Red nail matrix – personal observation Retronychia JAAD 73:849–855, 2015 Trachyonychia Dermatol Clin 33:243–255, 2015 Transient bullous dermolysis of the newborn Genetic Skin Disorders, Second Edition, 2010,pp.173–175 Transient yellow discoloration of nails Orphanet J Rare Dis 12:159, 2017 Twenty nail dystrophy Ped Derm 5:117–119, 1988; JAAD 7:349– 352, 1982

Aplasia cutis congenita with limb defects Genetic Skin Disorders, Second Edition, 2010,pp.455–460 Aplasia cutis congenita associated with fetus papyraceus – cutaneous ulcers, linear atrophic scars, atrophic scars of scalp, dystrophic nails Ped Derm 32:858–861, 2015 Asymmetric gait nail unit syndrome (AGNUS) – clinical changes of toenails identical to onychomycosis SKINmed 12:217–223, 2014 Bart-Pumphrey syndrome – palmoplantar keratoderma, knuckle pads, deafness, and leukonychia Cardiofaciocutaneous syndrome – shares findings of Costello syndrome such as cutis laxa, thin nails, curly hair, increased nevi, pruritus, hyperhidrosis Ped Derm 30:665–673, 2013 Cartilage-hair hypoplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.264–265 Cerebro-oculo-facial-skeletal syndrome (in aboriginal families) – onychogryphosis, microcephaly, facies – micrognathia, small eyes, enlarged ears, bulbous nose, prominent nasal bridge, microphthalmia with poor vision, cataracts, blepharophimosis, short palpebral fissures, photosensitivity, mental retardation, hyperkinesis, failure to

664 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 thrive, developmental delay, hypotonia, orthopedic anomalies (kyphoscoliosis), joint contractures; overhanging upper lip, small jaw JAAD 75:873–882, 2016; Ped Derm 26:97–99, 2009; JAMA Derm 149:1414–1418, 2013 CHAND syndrome – autosomal recessive; curly hair, ankyloblepharon, nail dysplasia; RIPK4 mutation Am J Med Genet A 173:3114– 3117, 2017; Genetic Skin Disorders, Second Edition, 2010, pp216–219 Chevron nails (herring bone nails) – congenital nail dystrophy with V-shaped abnormalities Society of Pediatric Dermatology Annual Meeting, July, 2015 CHILD syndrome Genetic Skin Disorders, Second Edition, 2010,pp.116–119 Chondrodysplasia punctate, X-linked (Conradi-Hunermann-Happle syndrome) Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.226–227 Cleidocranial dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.3–33 Clouston’s syndrome (hidrotic ectodermal dysplasia) – pterygium, thinning of nails J Dermatol 48:329–330, 2019; may mimic nail changes of pachyonychia congenita JID Cockayne’s syndrome (cachectic dwarfism) – autosomal recessive; thin skin, dry hair, anhidrosis, short stature, facial erythema in butterfly distribution leading to mottled pigmentation and atrophic scars, premature aged appearance with loss of subcutaneous fat and sunken eyes (enophthalmos with loss of periorbital fat), lipoatrophy of temples; canities, nail dystrophy, hair loss, mental deficiency, photosensitivity, disproportionately large hands, feet, and ears, ocular defects, demyelination JAAD 75:873–882, 2016; Ped Derm 20:538–540, 2003; J Med Genet 18:288–293, 1981 Coffin-Siris syndrome – mutation in ARID1B; extreme obesity, macrocephaly, hepatomegaly, hyperinsulinemia, polycystic ovarian syndrome, hypertrichosis, hypoplastic or absent fifth distal phalanx or nail Eur J Hum Genet 22:1327–1329, 2014; Am J Med Genet A176:1764–1767, 2018 Costello syndrome – warty papules around nose and mouth, legs, perianal skin; loose thick skin of neck, hands, and feet, thick, redundant palmoplantar surfaces, hypoplastic nails, short stature, craniofacial abnormalities; linear papillomatous papules of upper lip Ped Derm 30:665–673, 2013; BJD 168:903–904, 2013; Am J Med Genet 117:42–48, 2003; Eur J Dermatol 11:453–457, 2001; Am J Med Genet 82:187–193, 1999; JAAD 32:904–907, 1995; Am J Med Genet 47:176–183, 1993; Aust Paediat J 13:114–118, 1977 Cutis laxa (dermatochalasis connata) – autosomal dominant; mild disease of late onset Ped Derm 21:167–170, 2004; bloodhound appearance of premature aging Ped Derm 19:412–414, 2002; JAAD 29:846– 848, 1993; Clin Genet 39:321–329, 1991; Ped Derm 2:282–288, 1985 Craniofrontal dysplasia – longitudinal ridges Genetic Skin Disorders, Second Edition, 2010 Cronkhite-Canada syndrome – diarrhea, protein-losing enteropathy, and peripheral edema; atrophic fingernails NEJM 366:463–468, 2012 Curry-Hall syndrome – polydactyly Desmoplakin mutations – syndrome of dilated cardiomyopathy with severe left ventricular dysfunction, congenital alopecia, striate palmoplantar keratoderma, nail dystrophy, follicular hyperkeratosis with hyperpigmented plaques of elbows Ped Derm 32:102–108, 2015 DOOR syndrome (deafness and onychoosteodystrophy with mental retardation) Int J Ped Otorhinolaryngol 117:57–60, 2019 Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) – Xq28; oral leukoplakia, bullae and erosions; distal ridging, splitting,

pterygia BJD 178:335–349, 2018; JAAD 77:1194–1198, 2017; J Blood Med 5:157–167, 2014; Br J Haematol 145:164–172, 2009; Semin Cut Med Surg 16:72–80, 1997; Ped Derm 14:411–413, 1997; J Med Genet 33:993–995, 1996; Dermatol Clin 13:33–39, 1995; BJD 105:321–325, 1981 Autosomal recessive – hypotrichosis, dystrophic nails; HOXC13 Ped Derm 34:172–175, 2017 Ectodermal dysplasia – X-linked anhidrotic ectodermal dysplasia; thin or atrophic nails EEC syndrome Genetic Skin Disorders, Second Edition, 2010,pp.279–282 Ellis-van Creveld syndrome (achondroplastic dwarfism with defective teeth and nails, and polydactyly) (chondroectodermal dysplasia) – autosomal recessive; very short stature; chondrodysplasia, ectodermal dysplasia with ulnar polydactyly, cone- and peg-shaped teeth or hypodontia, enamel hypoplasia, fused incisors, molars with extra cusps, dental fissures and pits, neonatal teeth, malocclusion; short upper lip bound down by multiple labiogingival frenula; gingival hypertrophy, nail dystrophy, hair may be normal or sparse and brittle; cardiac defects; ichthyosis, palmoplantar keratoderma; asymmetric distal limb shortening; short distal phalanges with small dystrophic fingernails; congenital heart disease; hypospadias, cryptorchidism; mutations in EVC and EVC2 Cutis 83;303–305, 2009; Ped Derm 18:485–489, 2001; J Med Genet 17:349–356, 1980; Arch Dis Child 15:65–84, 1940 Erythrokeratoderma-cardiomyopathy syndrome – recurrent infections, wiry or absent hair, dental enamel defects, nail dystrophy, sudden onset congestive heart failure; early death; dominant mutation in desmoplakin Cases of the Year, Pre-AAD Pediatric Dermatology Meeting Finlay-Marks syndrome (scalp-ear-nipple syndrome) – nipple or breast hypoplasia or aplasia, aplasia cutis congenita of scalp, abnormal ears and teeth, nail dystrophy, syndactyly, reduced apocrine secretion Fried syndrome – autosomal recessive; thin sparse hair and eyebrows; everted lower lip GAPO syndrome Am J Med Genet A 146A:1523–1529, 2008; Genetic Skin Disorders, Second Edition, 2010,pp.284–286 Goltz’s syndrome (focal dermal hypoplasia) – atrophic nails; V-nicking; longitudinal ridging, micronychia; asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberry-like papillomas of lips, perineum, acrally, at perineum, buccal mucosa; xerosis; hypopigmented atrophic macules, Blaschko-esque hyperpigmentation, yellow nodules of hand, oligodontia, wide-spaced teeth, cleft hand, syndactyly, mammary hypoplasia, scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones; thin or atrophic nails JAMADerm 152:713–714, 2016; AD 148:85–88, 2012; AD 143:109–114, 2007; JAAD 25:879–881, 1991; AD 86:708–717, 1962; aplasia cutis congenita AD 145:218–219, 2009; male mosaic Goltz’s syndrome; blaschko-linear white atrophic depigmented lines, hyperpigmented linear streaks, linear alopecia, syndactyly, hydronephrosis Ped Derm 28:550–554, 2011; unilateral focal dermal hypoplasia, unilateral – PORCN gene mutation; PORCN encodes O-acyltransferase involved in palmitoylation and secretion of Wnt signaling proteins important in embryonic tissue development, fibroblast proliferation and osteogenesis Am J Med Genet C Semin Med Genet 172C:44–51, 2016; AD 148:85–88, 2012; AD 145:218–219, 2009 Hair-nail-skin-teeth dysplasias (dermo-odonto-dysplasia, pilo-dentoungular dysplasia, odonto-onycho-dermal dysplasia, odonto-onychial dysplasia, tricho-dermo-dysplasia with dental alterations) Am J Med Genet 14:335–346, 1983

Nail Abnormalities Huriez syndrome Clin in Dermatol 23:47–55, 2005 Hutchinson-Gilford syndrome – thin nails Genetic Skin Disorders, Second Edition, 2010,pp.649–653 Hypertrichosis, coarse face, brachydactyly, obesity, mental retardation, broad proximal phalanges, small dysmorphic nails Clin Dysmorphol 5:223–229, 1996 Hypohidrotic ectodermal dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.456–457

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nails, erythematous telangiectatic, reticulated atrophic malar and ala nasal patches with vermiculate scarring JAAD 57:732–733, 2007; Am J Med Genet 14:335–346, 1983 Olmsted syndrome Orphanet J Rare Dis March 17, 2015; Genetic Skin Disorders, Second Edition, 2010,pp.65–68 Onychodystrophy with deafness Genetic Skin Disorders, Second Edition, 2010,pp.246–248

Hydantoin-barbiturate embryopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.450–451

Onychomatricoma – parallel white and yellow nail bands with thickening of the nail plate; multiple subungual perforations JAAD 76:S19–21, 2017

Incontinentia pigmenti Genetic Skin Disorders, Second Edition, 2010,pp.311–316

Onychotrichodysplasia and neutropenia – thin nails Clin Genet 15:147–152, 1979

IPEX syndrome – immune dysregulation (neonatal autoimmune enteropathy, food allergies), polyendocrinopathy (diabetes mellitus, thyroiditis), enteropathy (neonatal diarrhea), X-linked, rash (atopic dermatitis-like with exfoliative erythroderma and periorificial dermatitis; psoriasiform dermatitis, pemphigoid nodularis, painful fissured cheilitis, edema of lips and perioral area, urticaria secondary to foods); penile rash; thyroid dysfunction, diabetes mellitus, hepatitis, nephritis, onychodystrophy, alopecia universalis; mutations in FOXP3 (forkhead box protein 3) gene – master control gene of T regulatory cells (Tregs); hyper IgE, eosinophilia JAAD 73:355–364, 2015; BJD 160:645–651, 2009; ichthyosiform eruptions Blood 109:383–385, 2007; BJD 152:409–417, 2005; NEJM 344:1758– 1762, 2001; alopecia areata AD 140:466–472, 2004

Otopalatal syndrome, type 1 – X-linked dominant Clin in Dermatol 23:47–55, 2005

Iso-Kikuchi syndrome – congenital onychodysplasia of the index finger Actas Dermosifiliogr 109:e33–36, 2018

PGM3 deficiency – autosomal recessive; dermatitis, conductive hearing loss, ataxia, myoclonus, narrow palpebral fissures; increased IgE; herpes simplex, molluscum contagiosum viral infections, sinopulmonary infections, chronic mucocutaneous candidiasis, developmental delay JAAD 73:355–364, 2015

Kindler’s syndrome – thin nails Genetic Skin Disorders, Second Edition, 2010,pp.636–666 Laband syndrome Genetic Skin Disorders, Second Edition, 2010,pp.190 Laryngo-onycho-cutaneous syndrome – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3 (LAMA3A) BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedica 2:15–25, 1986 Lelis syndrome – acanthosis nigricans with hypohidrosis, hypotrichosis, hypodontia, furrowed tongue, nail dystrophy, palmoplantar keratoderma Genetic Skin Disorders, Second Edition, 2010, pp.94–97 LOGIC syndrome Genetic Skin Disorders, Second Edition, 2010,pp.161,163 Multicentric reticulohistiocytosis – onychomadesis (shedding of nail) Naegeli-Franceschetti-Jadassohn syndrome – autosomal dominant; abnormally shaped teeth, polydontia, yellow spotted enamel, caries, early total loss; reticulate gray to brown pigmentation of neck, upper trunk and flexures, punctate or diffuse palmoplantar keratoderma, hypohidrosis with heat intolerance, onycholysis, subungual hyperkeratosis JAAD 60: 289–298, 2009; Ped Derm 22:122–126, 2005; Semin Cutan Med Surg 16:72–80, 1997; JAAD 28:942–950, 1993; Genetic Skin Disorders, Second Edition, 2010,pp.327–329 Nail patella syndrome – triangular lunulae J Drugs Dermatol 14:85–86, 2015; Indian J Dermatol Venereol Leprol 73:355–357, 2007; Clin in Dermatol 23:47–55, 2005 Odonto-onycho-dermal dysplasia – oligodontia with small widely spaced conical peg-shaped teeth, hypodontia, absence of secondary teeth; palmoplantar keratoderma, hyperhidrosis, dystrophic

Pachyonychia congenita – overcurvature of nails; subungual hyperkeratosis; facial steatocystoma multiplex and palmoplantar keratoderma; mutation in keratin 17 Ped Derm 36:149–151, 2019; BJD 171:1565–1567, 2014; BJD 171:343–355, 2014; JAMADerm 150:146–153, 2014; Clin in Dermatol 23:6–14, 2005 Pallister-Hall syndrome – autosomal dominant Clin in Dermatol 23:47–55, 2005 Papillon-Lefevre syndrome – splits, grooves, and pits Genetic Skin Disorders, Second Edition, 2010,pp.83–86 Peutz-Jeghers syndrome – brown pigmented bands of nails

POEMS syndrome – white nails Int J Dermatol 52:1349–1356, 2013 Pseudoglucagonoma syndrome – periorificial erythema, crusted migratory plaques, hair loss, brittle nails, diarrhea, poor weight gain, onycholysis; associated with cirrhosis, celiac disease inflammatory bowel disease, small cell lung cancers Am J Med 126:387–389, 2013 Psoriasis, pediatric Ped Derm 35:202–207, 2018 Pure hair and nail ectodermal dysplasia – autosomal dominant or autosomal recessive; alopecia of scalp; may be generalized; nail dystrophy; mutation in HOXC13 BJD 169:478–480, 2013 Pycnodysostosis – autosomal recessive Clin in Dermatol 23:47–55, 2005 Rabson-Mendenhall syndrome Genetic Skin Disorders, Second Edition, 2010, pp.197 Retronychia (disappearing nail bed) – hyperpigmentation of proximal nail fold Ped Derm 34:717–718, 2017 Revesz syndrome Genetic Skin Disorders, Second Edition, 2010, pp.303 Rothmund-Thomson syndrome Genetic Skin Disorders, Second Edition, 2010, pp.669–673 Rubinstein-Taybi syndrome – autosomal dominant Clin in Dermatol 23:47–55, 2005 Santos syndrome – ungula hypoplasia/anonychia J Hum Genetics 62:1073–1078, 2017 SASH1 related lentigines, hyper- and hypopigmentation, alopecia, nail dystrophy, palmoplantar keratoderma, skin cancer BJD 177:945–959, 2017 Schopf-Schulz-Passarge syndrome (hypotrichosis, palmoplantar hyperkeratosis, apocrine hidrocystomas of eyelid margins, nail dystrophy) – oligodontia; red palms and soles with focal dryness; maceration with hyperhidrosis; finger and toenail dystrophy; mutation in WNT10A BJD 171:1211–1214, 2014; Ped Derm

666 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 30:491–492, 2013; JAAD 65:1066–1069, 2011; AD 140:231–236, 2004; Acta DV 88:607–612, 2008; JAAD 10:922–925, 1984

Traumatic nail damage

Scleroatrophic and keratotic dermatosis of the limbs Genetic Skin Disorders, Second Edition, 2010,pp.87–89

VASCULAR LESIONS

Sclerosteosis – autosomal recessive Clin in Dermatol 23:47–55, 2005

Arteriovenous malformation, subungual – red lunulae

Simpson–Golabi–Behmel syndrome – generalized somatic overgrowth; coarse facial features, hypertelorism, downslanting palpebral fissures, epicanthal folds, short nose with broad nasal bridge, macrostomia, macroglossia, central groove of lower lip and/ or tongue; short broad hands, fingernail hypoplasia of index finger, supernumerary nipples Cutis 83:255–261, 2009 Temple-Baraitser syndrome – absent or hypoplastic first thumbnails and/or toenails Clin Dysmorphol 24:55–60, 2015; Am J Med Genet A 146A:450–452, 2008 Tooth and nail syndrome – thin nails Genetic Skin Disorders, Second Edition, 2010,pp.291–292 Trichorhinophalangeal syndromes types I and II – thin nails BJD 171:1581–1573, 2014; Genetic Skin Disorders, Second Edition, 2010,pp.225–228 Trichothiodystrophy Genetic Skin Disorders, Second Edition, 2010,pp.229–233 Turner’s syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.192–193 Weaver syndrome – generalized somatic overgrowth; macrocephaly, broad forehead, flattened occiput, large low set ears, hypertelorism; soft loose skin, redundant nuchal skin folds; umbilical hernia; thin deep set nails J Ped Genet 4:136–143, 2015; Cutis 83:255–261, 2009 Williams’ syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.484–485 Witkop tooth-nail syndrome – autosomal dominant; hypodontia with nail dysgenesis; teeth widely spaced; narrow crowns; hypoplastic spoon shaped nails, slow growing, prone to fracture; normal facies; mutation in MSX1 Ped Derm 28:281–285, 2011; Clin in Dermatol 23:47–55, 2005; J Clin Pediatr Dent 28:107–112, 2004; Oral Surg 37:576–582, 1974

Atherosclerosis and other vascular disorders – atrophic nails Blue rubber bleb nevus syndrome – personal observation Cholesterol emboli, splinter hemorrhages – personal observation Clubbing BJD 173:922–979, 2015 Dissecting aortic aneurysm – transverse white nail bands Glomus tumors – red nails, lunula Hemangioma, proliferating – including red nails Peripheral arterial disease – onychodystrophy J Vasc Nurs 34:24–26, 2016 Raynaud’s phenomenon – atrophic nails

 ASAL INFILTRATION OR N ENLARGEMENT  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic rhinitis Pemphigus vegetans Pemphigus vulgaris Cutis 34:394–395, 1984 Relapsing polychondritis – personal observation Rheumatoid nodule – nasal nodule JAAD 53:191–209, 2005; JAAD 8:439–457, 1983

CONGENITAL ANOMALIES Anterior cephalocele – intranasal polypoid lesion with broad nasal bridge Ped Derm 32:161–170, 2015

Yellow nail syndrome BJD 156:1230–1234, 2007; Clin in Dermatol 23:47–55, 2005; without a syndrome SKINMed 17:73–74, 2019

Dermoid cyst Ped Derm 36:745–746, 2019; AD 135:463–468, 1999

TOXINS

Embryonal rhabdomyosarcoma – orbit, nasopharynx, nose

Carbon monoxide – red lunulae Mee’s lines – arsenic poisoning; zebra stripes JAAD 50:258–261, 2004 Selenium toxicity – transverse white nail bands JAAD 63:168–169, 2010 Thallium poisoning – generalized hyperpigmentation; anagen effluvium, gastrointestinal upset, visual impairment, Mees’ lines, perioral dermatitis, scaling of palms and soles, acneiform eruptions; treat with Prussian blue JAMADerm 152:724–726, 2016

Dermoid sinus – broad nasal root Ped Derm 32:161–170, 2015; Dermatol Therapy 18:104–116, 2005 Encephalocele Epidermoid cyst – congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005 Hemangioma congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005 Heterotopic brain tissue Lacrimal duct cyst Lymphoma – congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005 Meningocele

TRAUMA

Meningoencephalocele Meningioma – extracranial meningioma

Beau’s lines Dermatol Clin 33:243–255, 2015; Arch Gen Med 11:447–458, 1846

Metastatic tumor – congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005

Habit tic deformity Dermatol Clin 33:243–255, 2015 zebra stripes

Nasal glioma (nasal glial heterotopia) – red or bluish nodules; resemble hemangiomas, nasal encephalocele, meningoencephalocele, extracranial meningioma, dermoid cyst, lacrimal duct cyst, neuroblastoma, rhabdomyosarcoma Ped Derm 25:573–574, 2008; Ear Nose Throat J 80:410–411, 2001

Hyperpigmentation – physical trauma, habit tic deformity, radiation Physical trauma – atrophic nails Ski jump toenails – primary lymphedema Vasc Med 20:268, 2015

Nasal Infiltration or Enlargement

667

Nasal midline masses Dermatol Therapy 18:104–116, 2005; AD 127:362–366, 1991

Histoplasmosis – indurated red nose JAAD 38:310–313, 1998; Mycopathologia 115:13–18, 1991

Neuroblastoma – olfactory neuroblastoma Soc Ped Derm Annual Meeting, Poster Session, July 2005

Leishmaniasis – mucocutaneous leishmaniasis – infiltrated nasal plaque JAMA 312:1250–1251, 2014;; lupoid leishmaniasis – verrucous plaque of nose JAAD 73:911–926, 2015; JAAD 73:897–908, 2015;indurated red nose (tapir face) JAAD 60:897–925, 2009; JAAD 38:310–313, 1998; Am J Trop Med Hyg 59:49–52, 1998; L. tropica – enlarged nose with crusted plaque JAAD 71:271–277, 2014; L. aethiopica – nasal infiltration with edema but no destruction Trans R Soc Trop Med Hyg 63:708–737, 1969; mucocutaneous leishmaniasis with destruction of the nose and midface JAAD 34:257, 1996

Neurofibroma – congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005 Olfactory neuroblastoma Rhabdomyosarcoma – congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005; J Cut Med Surg 13:276–279, 2009 Subcutaneous abscess – congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005

Leprosy – indurated red nose JAAD 38:310–313, 1998

Teratoma of nasal tip Ann Plast Surg 35:522–524, 1995

Mycobacterium avium-intracellulare – nasal papules JAAD 33:528–531, 1995

Trauma, facial congenital midline mass Soc Ped Derm Annual Meeting, Poster Session, July 2005

Mycobacterium marinum Medicine 95:e3131, 2016

DRUGS Methotrexate-associated lymphoproliferative disorder – red papules and plaques of nose, cheeks, eyelids JAAD 56:686–690, 2007

EXOGENOUS AGENTS

Mycobacterium tuberculosis – lupus vulgaris Clin Dermatol 32:817–826, 2014; indurated red nose Dermatol Clin 26:285–294, 2008; JAAD 38:310–313, 1998; starts as red-brown plaque; vegetating forms – ulcerate, areas of necrosis, invasion of mucous membranes with destruction of cartilage (lupus vorax); tumor-like forms – deeply infiltrative; soft smooth nodules or red-yellow hypertrophic plaque; nasal papules; Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960;

Silicone granulomas – nasal enlargement JAAD 52:S53–56, 2005

North American blastomycosis – pustulonodular infiltration of nose JAMA 312:2564–2565, 2014; indurated red nose JAAD 38:310– 313, 1998; Laryngoscope 103:53–58, 1993

Smoking-induced nasopharyngeal lymphoid hyperplasia Laryngoscope 107:1635–1642, 1997

Paracoccidioidomycosis – indurated red nose Dermatol Clin 26:257–269, 2008; JAAD 38:310–313, 1998 Pinta – Treponema carateum

INFECTIONS AND INFESTATIONS Abscess – nasal septal abscess – collection of pus between cartilaginous or bony septum and mucoperichondrium or periosteum; due to trauma; bilateral nasal obstruction, foreign body sensation, nasal pain, swelling and erythema of overlying skin, rhinorrhea, swollen upper lip, fever, headache, malaise J Emerg Med 46:e81, 2014; Pediatr and Neonatology 53:213–215, 2012; Ear, Nose, and Throat J 90:144–145, 2011; J Laryngol and Otol 124:1014–1016, 2010; Rhinology 47:476–477, 2009 Actinomycosis – indurated red nose JAAD 38:310–313, 1998 Aspergillosis Oral Surg Oral Med Oral Pathol 59:499–504, 1985 Bacillary angiomatosis Cutaneous Manifestations of Infection in the Immunocompromised Host, second Ed, Grossman, et al Balamuthiasis (Balamuthia mandrillaris) – amoebic infection of soft tissues and central nervous system; edematous erythematous infiltrated plaque of face, abdomen, extremities; nasal enlargement Clin Dermatol 32:744–751, 2014; JAAD 60:897–925, 2009; Advances Dermatol 23:335–350, 2007

Rhinoscleroma – Klebsiella rhinoscleromatis (Frisch bacillus) exudative stage with rhinorrhea; then proliferative stage with exuberant friable granulation tissue of nose (Hebra nose), pharynx, larynx; progresses to nodules; then fibrotic stage; Acta Otolaryngol 105:494–499, 1988; Cutis 40:101–103, 1987; indurated red nose JAAD 38:310–313, 1998 Rhinosporidiosis (Rhinosporidium seeberi) – soft polyps with minute white spots; Indian sand dredgers; intranasal and conjunctival red polypoid lesions; NEJM 380:1359, 2019; JAAD 53:931–951, 2005 Sinusitis, acute Sporotrichosis – indurated red nose JAAD 38:310–313, 1998; fixed cutaneous Staphylococcus aureus – nasal carriage with intranasal folliculitis or vestibulitis Subcutaneous zygomycosis (Conidiobolus) – very disfiguring JAAD 30:904–908, 1994 Syphilis, tertiary

Basidiobolus ranarum

Verruga peruana – Bartonella bacilliformis

Candidiasis – chronic mucocutaneous candidiasis

Yaws – tertiary yaws – hypertrophic proliferative periostitis of maxilla and nasal bridge (osseous form) (goundou); only in African children Ped Derm 27:364–367, 2010

Chromomycosis JAAD 53:931–951, 2005 Conidiobolus coronatus (rhinoentomophthoromycosis) Med Mycol 48:870–879, 2010

Zygomycosis (Basidiobolus coronatus) AD 141:1211–1213, 2005

Cryptococcosis – indurated red nose JAAD 38:310–313, 1998 Erysipelas Fusarium – of sinuses; nasal erythema with conjunctivitis JAAD 47:659–666, 2002 Herpes simplex virus Herpes zoster

INFILTRATIVE DISEASES Amyloid – rhinophyma-like Aesthetic Plast Surg 28:98–99, 2004; primary cutaneous nodular amyloid Cutis 91:271,283–284, 2014; Juvenile hyaline fibromatosis (infantile systemic hyalinosis) Ped Derm 23:458–464, 2006 Juvenile xanthogranuloma

668 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Langerhans cell histiocytosis Lichen myxedematosus Pseudolymphoma – personal observation

INFLAMMATORY DISEASES Crohn’s disease J Otolaryngol 14:399–400, 1985 Lymphocytoma cutis – idiopathic or due to Lyme borreliosis JAAD 38:877–905, 1998 Lymphoid hyperplasia of the nasal cavity in AIDS Ann Otolaryngol Chir Cervicofac 105:543–547, 1988 Pseudolymphomatous folliculitis – infiltration of columella JAAD 60:994–1000, 2009; Am J Surg Pathol 23:1313–1319, 1999; AD 124:1272–1273, 1276, 1988 Pyoderma vegetans (pseudoepithelioma of Azua; hyperinflammatory proliferative pyoderma; blastomycosis-like pyoderma) – ulcerated vegetative plaques and rhinophymatous changes of nose JAMADerm 150: 773–774, 2014; Arch Dermatol Syphilol 43:289– 306, 1898 Pyostomatitis vegetans – pustular lips and nose; erosive plaques of lips with yellow crusts; association with ulcerative colitis and Crohn’s disease JAMADerm 156:335, 2020 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) J Cutan Pathol 25:563–567, 1998; BJD 134:749–753, 1996 Sarcoid – rhinophymatous sarcoid J Drugs Dermatol 3:333–334, 2003; lupus pernio JAAD 66:699–716, 2012; JAAD 39:835–838, 1998; Lupus 1:129–131, 1992; JAAD 22:439–443, 1990

Leukemia J Laryngol Otol 106:261–263, 1992; chronic lymphocytic leukemia – red infiltrated nose with necrosis Cutis 80:208– 210, 2007; chronic lymphocytic leukemic infiltrates – rosacea-like appearance BJD 150:1129–1135, 2004; Am J Surg Pathol 20:1000–1010, 1996; CLL appearing as rhinophymatous rosacea BJD 163:443, 2010; angioimmunoblastic lymphoma – personal observation; HTLV-1 leukemia/lymphoma – personal observation Lymphoma; JAAD 38:310–313, 1998; Br J Haematol 97:821–829, 1997; primary cutaneous B-cell lymphoma – rhinophyma-like enlargement of nose AD 140:751–756, 2004; midline malignant B-cell lymphoma Cancer 70:2958–2962, 1992; angiocentric T-cell lymphoma JAAD 26:31–38, 1992; primary cutaneous peripheral T-cell lymphoma – nasal enlargement – rhinophyma-like AD 148:824–831, 2012; Ad 140:751–756, 2004; BJD 164:677–679, 2011; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 69:112–119, 2013; nasal type CD56 + natural killer cell/T-cell lymphoma BJD 142:1021–1025, 2000; primary cutaneous follicular center cell lymphoma JAAD 52:S73–75, 2005; cutaneous Richter syndrome (CLL rapidly developing into large cell lymphoma) BJD 153:833–837, 2005; primary cutaneous follicular center lymphoma JAAD 65:887–889, 2011; B-cell lymphomas (primary marginal zone lymphoma, chronic lymphocytic leukemia) mimicking rosacea or rhinophyma AD 148:824–831, 2012 Malignant eccrine spiradenoma Dermatol Surg 27:417–420, 2001 Malignant fibrous histiocytoma, myxoid Ear Nose Throat J 91:e3–5, 2012 Malignant histiocytosis J Clin Pathol 35:599–605, 1982

METABOLIC DISEASES

Melanocytic nevus, congenital

Acromegaly Pituitary 20:22–32, 2017

Melanoma – rhinophymatous amelanotic melanoma Cutis 79:383– 386, 2007 Meningioma

NEOPLASTIC DISEASES Aggressive intranasal carcinoma – edema and erythema of nose Cutis 42:288–293, 1988 Angiosarcoma – indurated red nose JAAD 54:883–885, 2006; Cutis 76:313–317, 2005; JAAD 38:310–313, 1998;JAAD 38:837–840, 1998; BJD 76:21–39, 1964; resembling rhinophyma JAAD 49:530– 531, 2003

Merkel cell carcinoma – reddish-blue nodules; legs, lip, eyelid, scalp, nose Histopathology 7:229–249, 1983 Metastasis – rhinophyma-like metastatic carcinoma Cutis 57:33–36, 1996 Microcystic adnexal carcinoma – rhinophyma-like Laryngorhinootologie 83:113–116, 2004 Nasal polyps

Basal cell carcinoma mimicking rhinophyma – indurated red nose JAAD 38:310–313, 1998

Nasal septal carcinoma – mimicking rosacea J Derm Surg 13:1021–1024, 1987

Carcinoma of the nasal columella Am J Surg 170:453–456, 1995

Nasopharyngeal carcinoma Laryngoscope 111:645–649, 2001

Carcinoma of the nasal vestibule Int J Radiat Oncol Biol Phys 10:627–637, 1984

Neuroblastoma Minim Invasive Neurosurg 44:79–84, 2001

Cellular neurothekeoma – papule Ped Derm 12:191–194, 1995 Chondroid syringoma – infiltrated nodule of ala nasi Dermatol Online J Nov 15, 2016; Ped Derm 24:505–507, 2007 Cylindromatosis, familial J Med Genet 35:841–845, 1988 Epidermoid cyst Folliculosebaceous cystic hamartoma – nasal nodule JAAD 34:77–81, 1996 Kaposi’s sarcoma – enlargement of tip of nose in AIDS mimicking pyogenic granuloma of the nasal mucosa J Laryngol Otol 112:280– 282, 1998 Keratoacanthoma, giant Am J Dermatopathol 36:252–257, 2014; Clin Exp Dermatol 36:369–371, 2011 Lacrimal duct cyst

Neurofibroma Neurothekeoma, atypical cellular – pink papule of the nasal tip AD 147:1342–1343, 2011 Osteosarcoma of the orbit Ophthal Plast Reconstr Surg 14:62–66, 1998 Plasmacytosis, mucocutaneous Med Cutan Ibero Lat Am 16:339– 342, 1988 Polyps Allergy 54 Suppl 53:7–11, 1999 Post-transplant lymphoproliferative disorder Ear Nose Throat Jan7, 2020 Proliferating trichilemmal tumor An Bras Dermatol 87:914–916, 2012 Rhabdomyomatous mesenchymal hamartoma – sessile mass of nostril Ped Derm 32:256–262, 2015

Nasal Infiltration or Enlargement Rhabdomyosarcoma

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Schwannoma No Shinkei Geka 20:1189–1194, 1992. Japanese

Fibropapule multiplex of the nose – a possible variant of Cowden’s disease Dermatology 192:379–381, 1996

Sebaceous adenoma

Fibrous dysplasia

Sebaceous carcinoma – rhinophyma-like BJD 124:283–284, 1991

Hereditary progressive mucinous histiocytosis JAAD 35:298–303, 1996

Sebaceous hyperplasia

Juvenile hyaline fibromatosis – bulbous nose Ped Derm 6:68–75, 1989; Am J Med Genet 26:123–131, 1987; infiltration and multinodularity of nose; mutation of capillary morphogenesis protein 2 gene BJD 157:1037–1039, 2007

Septal hamartoma Int J Ped Otorhinolaryngol 67:669–672, 2003 Spindle cell lipoma – facial asymmetry with deviated nasal tip JAMADerm 156:210–211, 2020 Striated muscle hamartoma of the nostril J Dermatol 22:504–507, 1995 Squamous cell carcinoma – personal observation Trichoepitheliomas, multiple BJD 95:225–232, 1976

PARANEOPLASTIC DISEASES Acrokeratosis paraneoplastica (Bazex syndrome) Cutis 55:233–236, 1995; Medicine 70:269–280, 1991

PRIMARY CUTANEOUS DISEASES Acne necrotica varioliformis Acne rosacea, granulomatous rosacea Actinic rhinophyma – personal observation Alopecia mucinosa Darier’s disease Granuloma faciale BJD 153:851–853, 2005; Am J Otolaryngol 4:184–186, 1983; diffuse enlargement of entire nasal surface Cutis 88:77–82, 2011; Dermatologica 105:85–99, 1952; Proc R Soc Med 38:125–126, 1945; rhinophyma-like granuloma faciale BJD 170:474–475, 2014; eosinophilic angiocentric fibrosis – infiltration of mucosal surface of nose; thought to be mucosal variant of granuloma faciale Granulosis rubra nasi G Ital DV 125:275–276, 1990 Malignant pyoderma AD 122:295–302, 1986 Rhinophyma – acne rosacea JAAD 74:1276–1278, 2016; JAAD 72:49–58, 2015; NEJM 367:1838, 2012; BJD 161:814–818, 2009; JAAD 57:551–554, 2007; nodular rhinophyma   Mimickers of rhinophyma   Amyloid Aesthetic Plast Surg 28:98–99, 2004   Angiosarcoma JAAD 49:530–531, 2003   Microcystic adnexal carcinoma Laryngorhinootologie 83:113– 116, 2004   Sebaceous carcinoma BJD 124:283–284, 1991   Metastases Cutis 57:33–36, 1996   Sarcoid J Drugs Dermatol 2:333–334, 2003

Lipoid proteinosis – papules Ped Derm 9:264–267, 1992 Mucopolysaccharidoses Muir-Torre syndrome Multicentric reticulohistiocytosis Hautarzt 46:118–120, 1995 Proteus syndrome J Craniofac Surg 6:151–160, 1995 Pseudohypoparathyroidism – depressed nasal bridge Ped Derm 9:11–18, 1993 Steatocystoma multiplex, congenital linear Ped Derm 17:136–138, 2000 Tetrasomy 13q – facies with long forehead, thick eyebrows, hypertelorism, broad nasal bridge, malposition of teeth, prominent central incisors with diastema, bilateral clinodactyly of fifth fingers Ped Derm 32:263–266, 2015 Treacher Collins-Franceschetti syndrome (mandibulofacial dysostosis) – autosomal dominant; prominent nose, sunken cheeks, stretching of skin to side of neck, recessed chin, large down-turned mouth, wide-spaced eyes with antimongoloid slants, lateral coloboma of lower eyelids, absent eyelashes of lower lids, hairline extended to cheeks, small and crumpled pinnae, with skin tags or blind pits between tragus and angle of the mouth; hypoplastic or deformed teeth in older children Ped Derm 23:511–513, 2006 Trichorhinophalangeal syndrome type I – autosomal dominant; slow growing scalp hair; receding frontotemporal hairline with high bossed forehead; facial pallor, pear-shaped bulbous nose, elongated philtrum, thin upper lip, receding chin, tubercle of normal skin below the lower lip, distension, and deviation with fusiform swelling of the PIP joints; brachydactyly of thumbs and great toes, clinodactyly; hip malformation, brachydactyly, prognathism, fine brittle slow growing sparse hair, eyebrows sparse laterally, dense medially, short stature; mutation in zinc finger nuclear transcription factor (TRPS1 gene) BJD 163:416–419, 2010; BJD 157:1021–1024, 2007; AD 137:1429–1434, 2001; JAAD 31:331–336, 1994; Ped Derm 10:385–387, 1993; Hum Genet 74:188–189, 1986; Helv Paediatr Acta 21:475–485, 1966 Trichorhinophalangeal syndrome type II – microcephaly with mental retardation, deep set eyes, exotropia, broad nasal bridge, thick ala nasi, cartilaginous exostoses, foot deformities, joint laxity; EXT gene BJD 157:1021–1024, 2007 Tuberous sclerosis – giant angiofibromas JAAD 67:1319–1326, 2012 Zimmermann-Laband syndrome J Oral Pathol Med 19:385–387, 1990

SYNDROMES Bonnet-Dechaume-Blanc syndrome – midfacial arteriovenous malformation

TRAUMA Trauma – nasal fracture

Branchio-oculo-facial syndrome – bulbous nose Ped Derm 12:24–27, 1995 Costello’s syndrome – nasal papillomas Ped Derm 30:665–673, 2013; Ped Derm 11:277–279, 1994 Cutaneous segmental heterotopic meningeal tissue with multifocal neural and mesenchymal hamartomas – skin colored pedunculated papules of forehead, eyelids, scalp, ala nasi; hypertrichotic heterotopic meningeal nodule BJD 156:1047–1050, 2007

VASCULAR DISEASES Agminated eruptive pyogenic granuloma-like lesions over congenital vascular stains (capillary malformations) Ped Derm 29:186–190, 2012 Angioendotheliosarcoma Acta DV 64:88–90, 1984 Angiofibromas (tuberous sclerosis) Angiomatous nevus

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Arteriovenous malformation

CONGENITAL DISEASES

Granulomatosis with polyangiitis

Nasal aplasia, heminasal aplasia with or without proboscis Syndromes of the Head and Neck, p. 585–586, 1990

Hemangioma – infantile hemangioma Sem Cut Med Surg 35:108– 116, 2016; BJD 168:837–843, 2013; Ped Derm 26:399–404, 2009; Ped Derm 25:193–195, 2008; diffuse hemangioma AD 139:869– 875, 2003

 ASAL SEPTAL ULCERATIONS/ N PERFORATIONS (RHINOPHAGIC ULCERATION) NEJM 352:609–615, 2005; Cutis 65:73–76, 2000

 UTOIMMUNE DISORDERS AND DISEASES A OF IMMUNE DYSFUNCTION Bullous pemphigoid Clin Dermatol 32:817–826, 2014 Dermatomyositis J Rheum 13:231–232, 1986; anti-MDA5 J Eur Dermatol 26:315–316, 2016 Hyper-IgE syndrome Clin Dermatol 32:817–826, 2014; J Invest Allergol Clin Immunol 3:217–220, 1993 IgG4 disease Ann Rheum Dis 73:1434–1436, 2014 Lupus erythematosus, systemic – acute exacerbation of SLE; discoid lupus erythematosus Clin Dermatol 32:817–826, 2014; Arch Otolaryngol 99:456–457, 1974

Noma neonatorum – deep ulcers with bone loss, mutilation of nose, lips, intraorally, anus, genitalia; Pseudomonas, malnutrition, immunodeficiency

DEGENERATIVE DISEASES Trigeminal trophic syndrome (Wallenberg’s syndrome) JAAD 67:325–327, 2012; AD 148:641–646, 2012; Cephalalgia 28:980– 985, 2008; J Eur Acad Dermatol Venereol 21:725–731, 2007; JAAD 55:359–361, 2006; JAAD 50:549–552, 2004; BJD 141:758– 759, 1999; Clin Exp Dermatol 21:299–301, 1996; AD 115:1118, 1979   Acoustic neuroma   Alcohol or glycerol injection of Gasserian ganglion  Astrocytoma   Cortical and brainstem infarctions   Herpes zoster ophthalmicus   Intracranial meningioma   Mycobacterium leprae neuritis   Postencephalitic parkinsonism   Posterior, inferior cerebellar artery insufficiency   Spinal cord degeneration  Syringobulbia  Trauma   Trigeminal rhizotomy   Vertebrobasilar insufficiency

Mixed connective tissue disease Pemphigus vulgaris Clin Dermatol 32:817–826, 2014 PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; atopy; recurrent sinopulmonary infections JAMADerm 151:627–634, 2015 Relapsing polychondritis – saddle nose deformity, red ears, and airway collapse NEJM 378:1715, 2018; NEJM 352:609–615, 2005; Chest 91:268–270, 1987; Medicine 55:193–216, 1976 Rheumatoid arthritis Int Med 58:3167–3171, 2019; Arthr Rheum 19:119–121, 1976; methotrexate-associated lymphoproliferative disorder Sclerederma Arthr Rheum 19:119–121, 1976 STING-associated vasculopathy with onset in infancy (SAVI) (type 1 interferonopathy) ((activated STING in Vascular and Pulmonary syndrome – autoinflammatory disease; red plaques of face and hands; chilblain-like lesions; atrophic plaques of hands, butterfly telangiectasias of cheeks, nose, chin, lips, acral violaceous psoriasiform, papulosquamous, and atrophic plaques of vasculitis and acral cyanosis (livedo reticularis of feet, cheeks, and knees), nodules of face, nose, and ears; distal ulcerative lesions with infarcts (necrosis of cheeks and ears), nasal septal perforation; gangrene of fingers or toes with ainhum, nasal septal perforation, nail dystrophy; polyarthritis; myositis small for gestational age; paratracheal adenopathy, abnormal pulmonary function tests; interstitial lung disease with fibrosis with ground glass and reticulate opacities; gain of function mutation in TMEM173 (stimulator of interferon genes); mimics granulomatosis with polyangiitis JAAD 74:186–189, 2016; Ped Derm 33:602–614, 2016; JAMADerm 151:872–877, 2015; NEJM 371:507–518, 2014

DRUGS Aflibercept Asia Pac J Clin Oncol 13:e179–180, 2017 Bevacizumab Am J Otolaryngol 38:354–355, 2017 Corticosteroids, topical Rhinology 36:128–132, 1998; J Pediatr 105:840–841, 1984; intranasal steroid (nasal sprays) Clin Dermatol 32:817–826, 2014; JAMA 253:2046, 1985 Ketamine ENT J 95:256, 2016 Methotrexate SKINMed 14:139–140, 2016; Ear Nose Throat J 88:e12–14, 2009 Nicorandil – ulcer of forehead and nasal columella BJD 171:662– 663, 2014 Sweet’s syndrome, drug-induced – red plaques, nasal ulcers, perianal ulcers – celecoxib JAAD 45:300–302, 2001 Vasoconstrictors (rhinitis medicamentosa)

EXOGENOUS AGENTS Agricultural aerosolized dust Arsenic Bromines Button batteries – foreign body in the nose J Otolaryngol 21:458– 460, 1992 Cement Chemical and industrial dusts Chlorines Cocaine abuse – ulceronecrotic nasoparanasal lesions; cocaine sniffing ulcer Clin Inf Dis 61:1840–1849, 2015; JAAD 69:135–142, 2013; AD 143:653–658, 2007; NEJM 352:609–615, 2005; Br Dent J 198:333–334, 2005; Cutis 65:73–76, 2000; mimicking midline

Nasal Septal Ulcerations/Perforations (Rhinophagic Ulceration)

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granuloma JAAD 59:483–487, 2008; Eur Arch Otorhinolaryngol 255:446–447, 1998; JAAD 32:286–287, 1995; J Rheumatol 17:838–840, 1990

2012; slowly progressive cutaneous rhinofacial and pulmonary mucormycosis due to Mucor irregularis Clin Inf Dis 56:993–995, 2013

Cyanides

Mycobacterium africanum Clin Inf Dis 21:653–655, 1995

Glass

Mycobacterium kansasii J Laryngol Otol 117:992–994, 2003

Heavy metal

Mycobacterium marinum Medicine 95:e3131, 2016

Hydrochloric acid

Mycobacterium tuberculosis – tuberculosis cutis orificialis Dermatol Clin 33:541–562, 2015; lupus vulgaris of external nose with nasal septal perforation Indian J Tuberc 57:157–159, 2010; vegetating forms – ulcerate, areas of necrosis, invasion of mucous membranes with destruction of cartilage (lupus vorax); saddle nose deformity; nasal involvement with friable nodules which ulcerate J Lab Physic 159:26–30, 2017; J Formos Med Assoc 106:953–955, 2007; NEJM 352:609–615, 2005; Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960

Lime Methamphetamine Iran J Otorhinolaryngol 25:53–56, 2013 Rice and grain elevator dust Salt Sulfuric acid

INFECTIONS

Myiasis J Dermatol 22:348–350, 1995

Alternariosis

North American blastomycosis – nasopharyngeal mutilation Laryngoscope 103:53–58, 1993

Amebiasis (Entamoeba histolytica) – nasal destruction with malodorous ulcer with gray-white necrotic base Cutis 90:310–314, 2012 Anthrax JAAD 50:549–552, 2004 Aspergillosis JAAD 50:549–552, 2004 Balamuthia mandrillaris (granulomatous amebic infection) – central facial destruction JAAD 50:S38–41, 2004; J Trop Med Hyg 70:666–669, 2004 Cancrum oris (noma) – nasopharyngeal mutilation J Craniofac Surg 12:273–283, 2001 Coccidioidomycosis Cryptococcosis

Paracoccidioidomycosis – nasopharyngeal ulceration and/or mutilation NEJM 352:609–615, 2005; JAAD 50:549–552, 2004 Phagedenic ulcer – due to Klebsiella Ped Derm 30:367–369, 2013 Purpureocillium lilacinum Indian J Otolaryngol Head Neck Surg 65:184–185, 2013 Rhinoentomophthoromycosis JAAD 50:S38–41, 2004 Rhinoscleroma – nasopharyngeal mutilation NEJM 352:609–615, 2005; Ped Derm 21:134–138, 2004; Acta Otolaryngol 105:494–499, 1988; Cutis 40:101–103, 1987; Wien Med Wochenschr 20:1–5, 1870

Cytomegalovirus

Rhinosporidiosis – nasopharyngeal mutilation NEJM 352:609–615, 2005

Diphtheria Clin Dermatol 32:817–826, 2014

Sporotrichosis JAAD 50:549–552, 2004

Fusarium falciforme – saddle nose deformity; immunosuppression Clin Inf Dis 68:705,707–709, 2019

Staphylococcus aureus Clin Dermatol 32:817–826, 2014

Glanders – Pseudomonas mallei – cellulitis which ulcerates with purulent foul-smelling discharge, regional lymphatics become abscesses; nasal and palatal necrosis and destruction and mutilation; metastatic papules, pustules, bullae over joints and face, then ulcerate; deep abscesses with sinus tracts occur; polyarthritis, meningitis, pneumonia Clin Dermatol 32:817–826, 2014

Subcutaneous phaeohyphomycosis – Corynespora cassiicola (plant pathogen of leaf spotting disease) in CARD9 deficiency BJD 174:176–179, 2016 Syphilis – congenital – destruction of nasal septum; tertiary (gumma) Arch Otolaryngol Rhinol 2:13–15, 2016; Dermatol Clin 24:497–507, 2006; NEJM 352:609–615, 2005;; tertiary nasal syphilis; endemic (bejel) – nasopharyngeal mutilation

Herpes simplex virus

Typhoid Clin Dermatol 32:817–826, 2014

Histoplasmosis NEJM 352:609–615, 2005; Mycopathologia 176:145–150, 2013; Mycopathologia 115:13–18, 1991

Yaws – nasopharyngeal mutilation (rhinopharyngitis mutilans) (gangosa) JAAD 54:559–578, 2006; AD 142:12–13, 2006;

HIV/AIDS Rhinology 37:93–95, 1999 Leishmaniasis – L. panamensis – ulcera de Bejuco JAAD 75:19–30, 2016; JAAD 73:897–908, 2015; espundia (mucocutaneous leishmaniasis) – nasopharyngeal ulceration and/or mutilation Clin Dermatol 32:744–751, 2014; JAAD 60:897–925, 2009; NEJM 352:609–615, 2005; Am J Trop Med Hyg 59:49–52, 1998; post-kala azar dermal leishmanoid Clin Dermatol 32:817–826, 2014; masquerading as granulomatosis with polyangiitis J Clin Rheumatol 16:125–128, 2010 Leprosy – lepromatous leprosy – misshapen nose with collapse of nose and saddle nose deformity; nosebleeds Ped Derm 32:863– 864, 2015; NEJM 352:609–615, 2005; primary diffuse lepromatous leprosy (la lepra bonita) JAAD 51:416–426, 2004; leprous trigeminal neuritis – nasopharyngeal mutilation Mucormycosis (rhino-orbito-cerebral mucormycosis) – central facial destruction, hematoma, and ecchymosis JAAD 65:241–243, 2011; JAAD 50:549–552, 2004; unilateral localized facial edema with slight erythema; within days goes on to necrosis JAAD 66:975–984,

INFLAMMATORY DISEASES Crohn’s disease Ear Nose Throat J 79:520–523, 2000 Lethal midline granuloma – nasopharyngeal mutilation Malignant pyoderma – papulopustules, skin ulcers, violaceous nodules with central necrosis, tongue, pharyngeal, and nasal ulcers AD 146:102–104, 2010; AD 98:561–576, 1968 Pyoderma gangrenosum Allergy Rhinol (Providence)6:122–124, 2015; Clin Dermatol 32:817–826, 2014; BJD 141:1133–1135, 1999 Sarcoid, ulcerative – nasopharyngeal mutilation Clin Dermatol 32:817–826, 2014; NEJM 352:609–615, 2005; Dermatology 199:265–267, 1999; JAAD 39:835–838, 1998; BJD 99(Suppl.16):54–55, 1978 Ulcerative colitis Inflamm Bowel Dis 18:e397–398, 2012

672 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

METABOLIC DISORDERS

SYNDROMES

Cryoglobulinemia J Laryngol Otol 110:668–669, 1996

Albright’s hereditary osteodystrophy (pseudohypoparathyroidism) – osteoma cutis – periarticular calcified or ossified nodules (ectopic ossification); short stocky build; round face; low flat nasal bridge; short neck, brachymetaphalangism and brachydactyly; developmental delay, cataracts, hearing loss, seizures, poor dentition, basal ganglia calcification, osteomalacia, rickets, osteoporosis JAMA Derm 149:975–976, 2013; JAAD 15:353–356, 1986; AD 104:636– 642, 1971; Medicine 37:317–352, 1958

Porphyria – congenital erythropoietic porphyria – mutilation of the nose due to photosensitivity Semin Liver Dis 2:154–63, 1982 Prolidase deficiency – autosomal recessive; peptidase D mutation (PEPD); increased urinary imidopeptides; leg ulcers, anogenital ulcers, short stature (mild), telangiectasias, recurrent infections (sinusitis, otitis); mental retardation; splenomegaly with enlarged abdomen, atrophic scarring, spongy fragile skin with annular pitting and scarring; dermatitis, hyperkeratosis of elbows and knees, lymphedema, purpura, low hairline, poliosis, canities, lymphedema, photosensitivity, hypertelorism, saddle nose deformity, frontal bossing, dull expression, mild ptosis, micrognathia, mandibular protrusion, exophthalmos, joint laxity, deafness, osteoporosis, high arched palate JAAD 62:1031, 1034, 2010; Ped Derm 13:58–60, 1996; JAAD 29:819–821, 1993; AD 127:124–125, 1991; AD 123:493–497, 1987

NEOPLASTIC Adenocarcinoma Clin Dermatol 32:817–826, 2014 Basal cell carcinoma BJD 158:1386–1388, 2008; NEJM 352:609– 615, 2005; Acta Pathol Microbiol Scand 88A:5–9, 1980 Chondrosarcoma Clin Dermatol 32:817–826, 2014 Leukemia Clin Dermatol 32:817–826, 2014 Lymphoma, including extranodal nasal NK T-cell lymphoma (nasal lymphoma, polymorphic reticulosis, lymphomatoid granulomatosis, and malignant (lethal) midline granuloma) JAAD 54:S192–197, 2006; JAAD 52:708–709, 2005; AD 133:1156–1157, 1997; Am J Surg Pathol 20: 103–111, 1996; angiocentric lymphoma Cancer 66:2407– 2413, 1990; B-cell lymphoma Clin Dermatol 32:817–826, 2014 Malignant epithelial and mesenchymal tumors (sarcomas) – nasopharyngeal mutilation Clin Dermatol 32:817–826, 2014 Malignant histiocytosis – mimicking lethal midline granuloma Pathol Res Pract 171:314–324, 1981 Melanoma Multiple myeloma Nasal polyps – nasopharyngeal mutilation Squamous cell carcinoma AD 143:889–892, 2007; NEJM 352:609– 615, 2005; associated with HPV-5 in epidermodysplasia verruciformis J Laryngol Otol 102:834–835, 1988

Anhidrotic ectodermal dysplasia – saddle-nose deformity Clin Dermatol 32:817–826, 2014 Anti-phospholipid antibody syndrome – nasal tip necrosis BJD 142:1199–1203, 2000 Behcet’s disease Clin Dermatol 32:817–826, 2014 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – annular erythematous edematous plaques of face and trunk which become purpuric and result in residual annular hyperpigmentation; limitation of range of motion with plaques over interphalangeal joints; periorbital edema with violaceous swollen eyelids, edema of lips (thick lips), lipoatrophy of cheeks, nose, and arms, chondritis with progressive ear and saddle nose deformities, hypertrichosis of lateral forehead, gynecomastia, wide spaced nipples, nodular episcleritis and conjunctivitis, epididymitis, myositis, aseptic meningitis; short stature, anemia, abnormal liver functions, splenomegaly, protuberant abdomen Ped Derm 28:538–541, 2011; JAAD 62:487–495, 2010 Hurler’s syndrome – saddle-nose deformity Clin Dermatol 32:817– 826, 2014 Laryngo-onycho-cutaneous syndrome – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3 (LAMA3A) BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedica 2:15–25, 1986 Pseudohypoparathyroidism type IA (Albright’s hereditary osteodystrophy) – subcutaneous nodule (osteoma cutis); short stature, round face, obesity, subcutaneous ossifications, bilateral brachydactyly, mental retardation, hypothyroidism, saddle nose deformity Ped Derm 33:675–676, 2016; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp188–189

PHOTODERMATOSES Hydroa vacciniforme – Clin Dermatol 32:817–826, 2014

TOXINS Alkaline dusts (soap powders)

PRIMARY CUTANEOUS DISEASES

Anhydrous sodium carbonate (soda ash)

Eosinophilic angiocentric fibrosis (variant of granuloma faciale) – red facial plaque with saddle nose deformity Clin Dermatol 32:817–826, 2014; BJD 152:574–576, 2005; Histopathology 9:1217–1225, 1985

Arsenic

Hydroa vacciniforme – saddle nose deformity Ped Derm 21:555– 557, 2004 Neurodermatitis – personal observation

Bromoderma – nasopharyngeal mutilation Capsaicin (active agent in capsicum) Chromium inhalation – chrome ulcers Am J Ind Med 26:221–228, 1994; chrome plating Occup Med (Lond) 48:135–137, 1998 Copper salts Dimethyl sulfate Fluorides Industrial irritants (nickel, chromium, copper, arsenic)

PSYCHOCUTANEOUS DISEASES

Iododerma – nasopharyngeal mutilation

Factitial dermatitis Clin Dermatol 32:817–826, 2014; JAAD 50:549–552, 2004

Lime Mercury organic compounds

Neck Lesions Snuff Soda ash Br J Ind Med 11:31–37, 1954

673

Hyper IgE syndrome – papular, pustular, excoriated dermatitis of scalp, buttocks, neck, axillae, groin; furunculosis; growth failure Clin Exp Dermatol 11:403–408, 1986; Medicine 62:195–208, 1983 IgG4 related disease J Dermatol 44:288–296, 2017

TRAUMA Digital trauma Nose picking with impacted foreign bodies Clin Dermatol 32:817– 826, 2014; rhinotillexomania AJNR 18:1949–1950, 1997 Recurrent cautery Surgery – postnasal surgery (rhinoplasty) Plas Reconstr Surg Dec 2019; external trauma Clin Dermatol 32:817–826, 2014; trophic ulcer following surgery – nasopharyngeal mutilation

Linear IgA disease (chronic bullous disease of childhood) JAAD 54:652–656, 2006 Lupus erythematosus – systemic LE; tumid lupus Medicine 97:e0375, 2018; JAAD 41:250–253, 1999; Am J Dermatopathol 21:356–360, 1999; bullous dermatosis of SLE (annular bullae) – face, neck, upper trunk, oral bullae Semin Arthr Rheum 48:83–89, 2018; JAAD 27:389–394, 1992; Ann Int Med 97:165–170, 1982; Arthritis Rheum 21:58–61, 1978; discoid lupus, subacute cutaneous lupus erythematosus – annular and polycyclic lesions Med Clin North Am 73:1073–1090, 1989; JAAD 19:1957–1062, 1988; neonatal SKINMed 17:76–78, 2019

VASCULAR DISEASES

Morphea

Eosinophilic granulomatosis with polyangiitis Clin Dermatol 32:817–826, 2014; Otolaryngol Head Neck Surg 88:85–89, 1980

Pemphigus foliaceus of children – arcuate, circinate, polycyclic lesions JAAD 46:419–422, 2002; Ped Derm 3:459–463, 1986

Hemangioma, infantile Clin Dermatol 32:817–826, 2014

Pemphigus vegetans – Rom J Morph Embryol 56:563–568, 2015

Lymphomatoid granulomatosis – destruction of midline nasal structures; necrotic plaque of nose; crateriform nodule of cheek JAMADerm 155:113–114, 2019

Pemphigus vulgaris – - personal observation

Vasculitis Vascular neoplasm Granulomatosis with polyangiitis Clin Dermatol 32:817–826, 2014; Laryngoscope 119:757–761, 2009; NEJM 352:609–615, 2005; NEJM 352:392, 2005AD 130:861–867, 1993; Ann Int Med 98:76–85, 1983 Takayasu’s arteritis Intern Med 48:48:1551–1554, 2009; Arthr Rheum 19:119–121, 1976 Trigeminal trophic syndrome (posterior inferior cerebellar artery syndrome) (Wallenberg’s syndrome) – nasal ulcers, facial ulcers JAAD 74:215–228, 2016; Dt X Nervenheilk 19:227–231, 1901

NECK LESIONS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – cosmetics, nail polish Contact Dermatitis 34:140–141, 1996; fragrances, necklaces Compositae dermatitis – lichenified dermatitis along posterior hairline airborne allergic contact dermatitis JAAD 15:1–10, 1986; airborne omeprazole Acta DV Croat 27:188–189, 2019 Atopic dermatitis – poikiloderma-like lesions of the neck J Dermatol 17:85–91, 1990 Autoimmune progesterone dermatitis S Afr Med J 17:48–50, 2016 Brunsting-Perry cicatricial pemphigoid – herpetiform plaques with scarring Lancet 381:320–332, 2013; J Dermatol 38:887–892, 2011; AD 75:489–501, 1957

Rheumatoid neutrophilic dermatitis AD 133:757–760, 1997 Sclerederma Sjogren’s syndrome – enlarged submandibular glands A Clinician’s Pearls and Myths in Rheumatology pp.107–130; ed John Stone; Springer 2009; annular erythema of forehead, temples, neck, and thigh Clin Exp Rheumatol 22:55–62, 2004 STAT1 gain of function mutation – most common cause of chronic mucocutaneous candidiasis; demodicidosis with facial papulopustular eruptions, blepharitis, chalazion, dermatitis of the neck, nail dystrophy, congenital candidiasis Ped Derm 37:159–161, 2020 Still’s disease Urticaria

CONGENITAL ANOMALIES Dermatol Therapy 18:104–116, 2005 Branchial cleft cyst, sinus and/or fistula; overlying anterior border of the sternocleidomastoid muscle Int J Oral Maxillofac Surg 25:449– 452, 1996; Int J Dermatol 19:479–486, 1980; confused with malignant or tuberculous lymphadenopathy, parotid or thyroid tumor, thymopharyngeal cyst, thyroglossal cyst, dermoid cyst, teratoma, carotid body tumor, hemangioma, neurofibroma Plastic Reconstruct Surg 100:32–39, 1997; Arch Otolaryngol Head Neck Surg 123:438– 441, 1997; J Pediatr Surg 24:966–969, 1989; Melnick-Fraser syndrome – preauricular pits, hearing loss, and renal anomalies Branchial cleft sinus – pit in lower third of the neck along anterior border of sternocleidomastoid muscle; skin tag at opening Clin Otolaryngol 3:77–92, 1978

Folliculitis – pustules covering neck J Drugs in Dermatol 12:369– 374, 2013

Branchial vestige (wattles) (cervical chondrocutaneous branchial remnants) (cartilaginous rest of the neck (wattle)) – neck nodule in children – remnants include cysts (deep to middle or lower thirds of sternocleidomastoid muscles), sinus tracts, and cartilaginous remnants (overlying anterior border of sternocleidomastoid muscles); pinpoint firm masses or ear-like projections; (accessory tragus) (wattle or cervical auricle) AD 134:499–504, 1998; Ped Clin North Amer 6:1151–1160, 1993; Cutis 58:293–294, 1996; Int J Derm 25:186–187, 1986; AD 127:404–409, 1985; JDSO 7:39–41, 1981

Graft vs. host disease, acute – papules Taiwan I Hsueh Hui Tsa Chih 88:657–672, 1989; pediatric – red macules or folliculocentric papules of face, ears, palms and soles, periungual areas, upper back and neck AD 143:67–71, 2007

Bronchogenic cyst – keratotic papule, sinus tract or cyst at the suprasternal notch; neck, shoulders, back and chest AD 136:925– 930, 2000; Ped Derm 15:277–281, 1998; Ped Derm 12:304–306, 1995; J Cutan Pathol 12:404–409, 1985

Bullous pemphigoid Dermatitis herpetiformis – - personal observation Dermatomyositis – erythema of neck Epidermolysis bullosa acquisita

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Cervical braid Br J Plastic Surg 43:369–370, 1990

DRUG REACTIONS

Cervical chondrocutaneous branchial remnants – rare benign congenital choristomas Head Neck Pathol 12:244–246, 2018

Bleomycin – pruritic hyperpigmented patches of neck, back, chest, thighs; not flagellate BMJ Case Rep Sept 29, 2016

Cervical tab Cervico-thymic cyst – resembles branchial cleft cyst Congenital rhabdomyomatous mesenchymal hamartoma (striated muscle hamartoma) – skin colored pedunculated (polypoid) nodule of neck, midline of chin, upper lip Ped Derm 16:65–67, 1999; Ped Derm 7:199–204, 1990; Ped Derm 3:153–157, 1986 Cystic hygromas Cystic hygroma (lymphatic malformation) Ped Clin North Amer 6:1151–1160, 1993; NEJM 309:822–825, 1983 Cystic teratoma – large neck mass Dermoid cyst – lower neck Ped Derm 36:999–1001, 2019; neck, midline Ped Clin NA 6:1151, 1993; midline of nose, lateral eyebrow, scrotum, sternum, perineal raphe, and sacral areas Curr Prob in Derm 8:137–188, 1996; Acta Neurochir (Wien) 128:115–121, 1994; submental mass BJD 158:415–417, 2008 Ectopic thyroid gland NEJM 363:1351, 2010 Ectopic respiratory epithelium – red plaque of the neck BJD 136:933–934, 1997 Ectopic or christomatous salivary gland (heterotopic salivary gland tissue) – skin colored nodule along lower surface of the sternocleidomastoid muscle JAAD 58:251–256, 2008

Bortezomib (proteasome inhibitor for treatment of myeloma) – red nodules of trunk, face, neck, and extremities JAAD 55:897–900, 2006 Cetuximab – personal observation Corticosteroid – topical steroid acne – - personal observation Cyclosporine – acne keloidalis nuchae BJD 143:465–466, 2000 Efavirenz – HIV and HAART; bullfrog neck (HIV lipodystrophy) AD 146:1279–1282, 2010 Erlotinib – pustules of neck JAAD 147:735–740, 2011 Infliximab – symmetrical drug related intertriginous and flexural exanthems (baboon syndrome) J Dermatol Case Rep 31:12–14, 2015 Penicillamine – elastosis perforans serpiginosa AD 138:169–171, 2002 Protease inhibitor (saquinavir, nelfinavir, indinavir) – buffalo hump JAAD 46:284–293, 2002 Proton pump inhibitors – airborne contact dermatitis; red face and neck Dermatitis 26:287–290, 2015 Sirolimus (Rapamune) – acneiform eruptions of face, neck, and trunk JAAD 55:139–142, 2006

Ectopic thyroid tissue Ped Clin North Amer 6:1151–1160, 1993; large midline subcutaneous nodule NEJM 363:1351, 2010

Thalidomide embryopathy Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.370–371

Esophageal diverticulum

Vancomycin – linear IgA disease – - personal observation

Fibrous hamartoma of infancy – blue plaque of neck AD 144:547– 552, 2008

Vemurafenib – erythema and edema of face and neck BJD 169:934–938, 2013

Fourth branchial sinus causing recurrent cervical abscess Aust N Z J Surg 67:119–122, 1997 Laryngocele Midline cervical clefts – vertically oriented atrophic area of lower anterior neck, associated skin tags or sinus tracts, fibrous bands connect to platysma muscle Ped Derm 17:118–122, 2000; Int J Derm 19:479–486, 1980 Myelomeningocele Ped Derm 26:688–695, 2009 Nevus simplex (capillary ectasias) – glabella, eyelids, nose, upper lip, nape of neck Occult spinal dysraphism – papule Ped Derm 12:256–259, 1995 Pterygium colli medianum Rhabdomyomatous mesenchymal hamartoma – pedunculated papule associated with a midline cervical cleft AD 141:1161–1166, 2005 Teratoma – bulky tumors of newborn Ped Clin North Amer 6:1151– 1160, 1993 Thymopharyngeal cyst Thyroglossal duct cyst and/or sinus – midline cervical mass Ped Clin North Amer 6:1151–1160, 1993; J Pediatr Surg 24:966–969, 1989; cleft with sinus tract JAAD 26:885–902, 1992; J Pediatr Surg 19:437–439, 1984 Thyroid gland – enlarged pyramidal lobe of the thyroid gland Ped Clin North Amer 6:1151, 1993

EXOGENOUS AGENTS Chrysiasis – papules BJD 133:671–678, 1995 Fiberglass dermatitis Kao Hsiung I Hseveh Ko Hseueh Tsa Chih 12:491–494, 1996 Filler (PDMS) (liquid silicone) migration – erythema and edema over cheeks and neck following lip augmentation J Cosmet Dermatol 17:996–999, 2018 Impaled tree branch NEJM 373:366, 2015 Iodide mumps – iodine contrast agent; giant acute inflammatory swelling of submandibular, sublingual, or parotid glands Ann Int Med 145:155–156, 2006; Circulation 104:2384, 2001; Acta Radiol 36:82–84, 1995; Am J Roentgenol 159:1099–1100, 1992; JAMA 213:2271–2272, 1970; NEJM 255:433–434, 1956 Iododerma Australas J Dermatol 29:179–180, 1988 Methylene blue phototoxicity – erythema of anterior neck BJD 166:907–908, 2012 Mudi-chood – due to oils applied to hair; papulosquamous eruption of nape of neck and upper back; begin as follicular pustules then brown-black papules with keratinous rim Int J Dermatol 31:396–397, 1992 Percutaneous long line – extravascular location; neck ulcer in infant AD 147:512–514, 2011

Wattle (cervical accessory auricle) – - personal observation

INFECTIONS AND INFESTATIONS DEGENERATIVE LESIONS Cervical trophic syndrome JAAD 63:724–725, 2010

Abscess of neck – Salmonella Head Neck 13:153–155, 1991 Actinomycosis, cervicofacial – - midline cervical cleft with sinus tract Laryngoscope 94:1198–1217, 1984

Neck Lesions AIDS – photosensitivity Anthrax – eschar of neck NEJM 372:954–962, 2015; Cutis 67:488–492, 2001; J Appl Microbiol 87:303, 1999; Clin Inf Dis 19:1009–1014, 1994; Cutis 48:113–114, 1991; Cutis 40:117–118, 1987 Bacterial lymphadenitis

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Molluscum contagiosum – giant ulceroproliferative neck lesion Diagn Cytopathol 46:794–796, 2018 Mycobacterium avium – intracellulare Ped Clin North Amer 6:1151–1160, 1993 Mycobacterium bovis – scrofuloderma JAMADerm 155:610, 2019

Beetle (Paederus dermatitis) – severe vesicating dermatitis Mil Med 180:e1293–1295, 2015

Mycobacterium fortuitum – following neck liposuction Dermatol Surg 26:588–590, 2000; red plaque mimicking lupus vulgaris BJD 147:170–173, 2002

Brucellosis

Mycobacterium scrofulaceum Ped Clin NA 6:1151–1160, 1993

Candidiasis – personal observation

Mycobacterium tuberculosis – scrofuloderma – infected lymph node, bone, joint, lacrimal gland with overlying red-blue nodule which breaks down, ulcerates, forms fistulae, scarring with adherent fibrous masses which may be fluctuant and draining Cutis 85:85– 89, 2010; Dermatol Therapy 21:154–161, 2008; JAAD 54:559–578, 2006; BJD 134:350–352, 1996; Ped Clin North Amer 6:1151–1160, 1993; scrofuloderma after BCG vaccination Ped Derm 19:323–325, 2002; J Dermatol 21:106–110, 1924; tuberculous cervical adenitis Ped Derm 37:29–39, 2020; tuberculous cold abscess of the neck JAMADerm 150:909–910, 2014; BJD 142:387–388, 2000; massive tuberculous lymphadenopathy (red nodule) of lower neck in paradoxical response to anti-tuberculous therapy associated with infliximab treatment Clin Inf Dis 40:756–759, 2005; lupus vulgaris – vegetative linear serpiginous lesion of neck Ped Derm 36:955–957, 2019

Carbuncle Cat scratch disease Ped Clin NA 6:1151–1160, 1993 Chromomycosis AD 113:1027–1032, 1997; BJD 96:454–458, 1977; AD 104:476–485, 1971 Coccidioidomycosis AD 1345:365–370, 1998 Corynebacterium diphtheriae – respiratory diphtheria; pharyngeal erythema with purulent exudate; swollen neck NEJM 369:1544, 2013 Cryptococcosis – supraclavicular mass Head and Neck 21:239– 246, 1999; crusted plaque of neck AD 142:921–926, 2006 Cutaneous larva migrans Mikrobiyol Bul 50:165–169, 2016 Demodicidosis (demodex folliculitis) – erythema of face and neck mimicking acute graft vs. host reaction JAMA Derm 149:1407–1409, 2013; Bone Marrow Transplant 37:711–712, 2006; papular eruption in HIV patients of head and neck J Med Assoc Thai 74:116–119, 1991; JAAD 20:197–201, 1989 Dental sinus – midline cervical cleft with sinus tract J Derm Surg Oncol 7:981–984, 1981; JAAD 2:521–524, 1980 Diphtheria – swollen neck, fever, throat pain, difficulty swallowing, oral gray-white membrane, myocarditis NEJM 381:1267, 2019 Eikenella corrodens – neck wound Clin Inf Dis 33:70–75, 2001 Emergomyces pasteruianus Mycopathologia 185:193–200, 2020 Herpes simplex; eczema herpeticum (Kaposi’s varicelliform eruption) Clin Inf Dis 32:1480, 1500–1501, 2001;; Arch Dis Child 60:338–343, 1985; herpes simplex folliculitis – - personal observation Herpes zoster Histoplasmosis Horse fly bites J Travel Med Sept, 2017 Impetigo Infectious eczematoid dermatitis Infectious mononucleosis Ped Clin NA 6:1151–1160, 1993 Kaposi’s varicelliform eruption Leishmaniasis – red plaque – mucocutaneous leishmaniasis JAMA 312:1250–1251, 2014; nodule, crusting, ulceration, scarring Trans R Soc Trop Med Hyg 81:606, 1987; Cutis 38:198–199, 1986; L. donovani J Trop Med May 27, 2019 Lemierre’s syndrome (human necrobacillosis) – Fusobacterium necrophorum; suppurative thrombophlebitis of tonsillar and peritonsillar veins and internal jugular vein; oropharyngeal pain, neck swelling, pulmonary symptoms, arthralgias Clin Inf Dis 31:524–532, 2000 Lobomycosis Emerging Infect Dis 25:654–660, 2019 Ludwig’s angina – submandibular, submental swelling and edema of floor of mouth NEJM 381:163, 2019

Myiasis – Dermatobia hominis; abscess of posterior neck JAAD 57:716–718, 2007 Necrotizing fasciitis of neck Int J Surg Case Rep 59:220–223, 2019 Nocardiosis Cutis 104:226–229, 2019 North American blastomycosis Orf Acta DV Croat 27:280–281, 2019 Paracoccidioidomycosis – massive cervical adenopathy JAAD 53:931–951, 2005; Br J Radiol 72:717–722, 1999; cutaneous nodules Annual Meeting AAD 2000 Pasteurella multocida Pediculosis Phaeoacremonium inflatipes – fungemia in child with aplastic anemia; swelling and necrosis of lips, periorbital edema, neck swelling Clin Inf Dis 40:1067–1068, 2005 Pityrosporum folliculitis Mycoses 40(suppl 1):29–32, 1997 Plague Rat-bite fever Roseola infantum (human herpesvirus 6) – rose-pink macules start on neck and trunk, then spread to face and extremities Scabies, nodular Ped Derm 11:264–266, 1994; crusted scabies; Iran J Public Health 48:1169–1173, 2019 Sporotrichosis – cutaneous lesions with or without cervical lymphadenopathy; head and neck most frequent in children J Chiliena Infectol 33:315–321, 2016; JAAD 53:931–951, 2005 Staphylococcus aureus – folliculitis; furunculosis; staphylococcal lymphadenitis Head and Neck 21:239–246, 1999 Subcutaneous phaeohyphomycosis – Cladosporium cladosporioides; cysts and nodules of the face and neck for 5 years; Mycopathologia 181:567–573, 2016 Sycosis barbae

Lymphadenopathy, reactive – supraclavicular mass Head and Neck 21:239–246, 1999

Syphilis – primary chancre; secondary AD 133:1027, 1030, 1997; leukoderma syphiliticum JAAD 55:187–189, 2006; secondary – most commonly involved body site was the neck Int J STD AIDS 29:1454–1456, 2018

Mucormycosis – red plaque of neck Cutis 89:167–168, 2012

Tinea corporis

Lymphadenitis Ped Clin North Amer 6:1151, 1993

676 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Tinea versicolor Indian J Pathol Microbiol 59:159–165, 2016

Goiter

Toxoplasmosis

Verruga peruana Am J Trop Med and Hygiene 50:143, 1994

Pellagra (niacin deficiency) – Casal’s necklace; red pigmented sharply marginated photodistributed rash, including drug-induced pellagra-like dermatitis – 6-mercaptopurine, 5-fluorouracil,INH (all of the above – also seborrheic dermatitis-like); resembles Hartnup disease NEJM 371:2218–2223, 2014; Cutis 68:31–34, 2001; Ped Derm 16:95–102, 1999; BJD 125:71–72, 1991

INFILTRATIVE DISEASES

Porphyria – porphyria cutanea tarda with calcinosis; congenital erythropoietic porphyria BJD 148:160–164, 2003; bullae, erosions and crusts of neck and hands Dermatol Ther 32:e13014, 2019

Amyloidosis – nodular amyloidosis AD 139:1157–1159, 2003

Pregnancy – hyperpigmentation of neck, nipples, anogenital skin

Colloid milium Clin Exp Dermatol 18:347–350, 1993; BJD 125:80– 81, 1991

Pretibial myxedema JAAD 46:723–726, 2002

Trichophytosis barbae Indian J Med Microbiol 33:444–447, 2015 Tularemia Verruca vulgaris

Mastocytosis – - personal observation Juvenile xanthogranuloma (generalized lichenoid juvenile xanthogranuloma) – face, neck, scalp, upper trunk Child Nerv Syst 34:765–770, 2018; BJD 126:66–70, 1992; multiple BMJ Case Rep July 1, 2019

Pruritic urticarial papules and plaques of pregnancy Z Hautkr 65:831–832, 1990 Xanthomas, including plane xanthomatosis BJD 133:961–966, 1995; eruptive Acta Med Port 31:219–222, 2018 Acquired zinc deficiency – - personal observation

Langerhans cell histiocytosis – in adults SKINMed 14:147–149, 2016

NEOPLASTIC DISEASES

Scleredema, diabetes-associated – swollen neck JAMA 315:1159– 1160, 2016

Acrochordon (skin tags)

Xanthoma disseminatum Iran J Otorhinolaryngol 29:365–368, 2019

Actinic keratosis Adenoid cystic carcinoma JAAD 17:113–118, 1987 Angiomatoid fibrous histiocytoma Dermatol Surg 26:491–492, 2000

INFLAMMATORY DISEASES Eosinophilic pustular folliculitis J Dermatol 25:178–184, 1998

Apocrine carcinoma Cancer 71:375–381, 1993; carcinoma erysipelatoides (red plaque of head and neck) AD 147:1335–1337, 2011

Folliculitis nuchae scleroticans Hautarzt 39:739–742, 1988

Atypical fibroxanthoma Auris Nasus Larynx 42:469–471, 2015

Hidradenitis suppurativa – nodulocystic lesions of posterior neck and post-auricular areas AD 147:1343–1344, 2011

Basal cell carcinoma Cancer 92:354–358, 2001; following radiotherapy AD 108:523–527, 1973

Malignant pyoderma Pseudofolliculitis barbae

Basosquamous carcinoma Otolaryngol Head Neck Surg 87:420– 427, 1979

Rosai-Dorfman disease – sinus histiocytosis with massive lymphadenopathy

Blastic plasmacytoid dendritic cell neoplasm Rev Med Chil 145:1208–1212, 2017

Sarcoid – mask-like hypopigmented plaque of posterior neck The Dermatologist; February 2015; p.47–50; Laryngoscope 87:2038– 2048, 1977; subcutaneous sarcoid World J Clin Cases 7:2505– 2512, 2019

Bowenoid papulosis – neck papules JAAD 41:867–870, 1999

Toxic epidermal necrolysis

Carotid body tumor Cephalic histiocytomas Am J Dermatopathol 15:581–586, 1993 Chondroid syringoma Ear Nose Throat J 75:104–108, 1996 Collagenoma – linear Ped Derm 26:626–628, 2009; Pacinian collagenoma (form of sclerotic fibroma) J Cut Pathol 47:291–2020

METABOLIC DISEASES

Cylindromas – scalp, face, nose, around ears, and neck

Acrodermatitis enteropathica – - personal observation

Cysts on neck   Branchial cleft anomaly (cyst, sinus, and/or fistula)   Bronchogenic cyst   Dermoid cyst   Epidermoid cyst   Eruptive vellus hair cysts   Heterotopic salivary gland tissue  Milia   Pilar cyst   Steatocystoma multiplex/simplex    Thyroglossal duct cyst  Teratomas

Chronic alcoholism – telangiectatic mats – - personal observation Alpha-1 anti-trypsin panniculitis Congenital disorders of glycosylation (CDG-Ix) – nuchal skin folds, facial dysmorphism, inverted nipples, hypoplastic nails, petechiae and ecchymoses, edema; neurologic, gastrointestinal and genitourinary abnormalities, pericardial effusion, ascites, oligohydramnios Ped Derm 22:457–460, 2005 Congenital dyserythropoietic anemia type I – small or absent nails; partial absence or shortening of fingers and toes, mesoaxial polydactyly, syndactyly of hands and feet; short stature, vertebral abnormalities and Madelung deformity; mutation in CDAN1 Clin Exp Dermatol 515–517, 2020

Deep penetrating nevus JAAD 71:1234–1240, 2014 Dermatofibrosarcoma protuberans Oncol Lett 10:3765–3768, 2015

Cryoglobulinemia – papules JAAD 25:21–27, 1991

Dermatosis papulosa nigra Int J Derm 56:975–980, 2017

Essential fatty acid deficiency

Desmoplastic trichoepithelioma Acta DV Croat 27:282–284, 2019

Fabry’s disease – telangiectasias of the neck J Dermatol 33:652– 654, 2006

Epidermal nevus

Neck Lesions Epidermoid inclusion cyst

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Eruptive fibromas J Cut Pathol 25(2):122–125, 1998

dual positive cutaneous peripheral C-cell lymphoma Am J Dermatopathol 40:836–840, 2018

Eruptive histiocytoma J Dermatol 20:105–108, 1993

Lymphoplasmacytoid immunocytoma Hautarzt 44:172–175, 1993

Eruptive syringomas

Malignant proliferating trichilemmal tumor BJD 150:156–157, 2004

Eruptive vellus hair cysts Ped Derm 5:94–96, 1988 Ganglioneuroma of cervical sympathetic chain Ped Clin North Amer 6:1151–1160, 1993

Medallion-like dermal dendrocyte hamartoma – blue-brown oval depression of back of neonate; thin hair on surface AD 142:921– 926, 2006; of neck JAAD 51:359–363, 2004; wrinkled pliable pink-yellow atrophic patch with plucked chicken appearance of lateral neck Ped Derm 27:638–642, 2010

Giant cell fibroblastoma of soft tissue – neck and trunk Ped Derm 18:255–257, 2001

Melanoma Dermatology Nov 8, 2019; Acta Oncol 38:1069–1074, 1999; Am J Trop Med and Hygiene 50(2):143, 1994

Heterotopic submandibular salivary glands – submental mass Ped Clin North Amer 6:1151–1160, 1993

Merkel cell carcinoma Arch Plast Surg 46:441–448, 2019

Fibroblastic connective tissue nevus J Cut Pathol 44:827–834, 2017

Benign cephalic histiocytosis – neck papules AD 135:1267–1272, 1999

Metastases – supraclavicular masses; breast, uterine, cervical, lung, stomach, oropharyngeal carcinomas Head and Neck 21:239–246, 1999; carcinoma erysipelatoides – violaceous plaques of neck and upper chest AD 147:345–350, 2011; carcinoma en cuirasse (gastric) BMJ Case Rep April 30, 2019

Inflammatory linear verrucous epidermal nevus (ILVEN)

Mucoepidermoid carcinoma Laryngoscope 93:464–467, 1983

Infantile myofibromatosis – red to skin-colored nodules AD 134:625–630, 1998

Neurilemmoma

Hibernoma – neck, axilla, central back; vascular dilatation overlying lesion NEJM 367:1636, 2012; AD 73:149–157, 1956

Inverted follicular keratosis J Clin Pathol 28:465–471, 1975

Neuroblastoma of cervical sympathetic chain – neck mass Ped Clin North Amer 6:1151–1160, 1993

Kaposi’s sarcoma Int J Dermatol 58:1388–1397, 2019; Otolaryngol Head Neck Surg 111:618–624, 1994; Ann Int Med 103:744–750, 1985

Neurofibroma – plexiform neurofibromas of brachial plexus Ped Clin North Amer 6:1151–1160, 1993

Keloids – personal observation

Neuroma – hypercellular encapsulated neuroma Am J Dermatopathol 41:358–260, 2019

Keratoacanthoma, including Ferguson-Smith tumors Ann Dermatol Venereol 104:206–216, 1977; solitary giant keratoacanthoma Dermatol Surg 43:810–816, 2017 Leukemia cutis Laryngoscope 86:1856–1863, 1976; cervical adenopathy Ped Clin North Amer 6:1151–1160, 1993

Neurothekeoma Am J Surg Pathol 14:113–120, 1990 Nevi, melanocytic, including eruptive melanocytic nevi (papules) JAAD 37:337–339, 1997; J Dermatol 22:292–297, 1995 Nevus comedonicus Dermatol Online J Sept 15, 2016

Lipofibromata, eruptive AD 119:612–614, 1983

Nevus sebaceous

Lipoma supraclavicular mass Head and Neck 21:239–246, 1999; spindle cell lipomas JAAD 48:82–85, 2003; large neck mass in infancy

Nevus spilus Dermatol Ther July 30, 2014

Liposarcoma – swollen neck NEJM 363:864, 2010 Lymphadenoma, cutaneous – papules or nodules of head and neck BJD 128:339–341, 1993; adamantoid variant of trichoblastoma J Cut Pathol 44:954–957, 2017 Lymphadenopathy, malignant Lymphoma – cutaneous T-cell lymphoma; folliculotropic CTCL – red plaque of face (periauricular), head, neck; comedo-like lesions, acneiform, cystic, follicular keratotic papules JAAD 62:418–426, 2010; and Ki-1+ lymphoma; anaplastic large cell B-cell lymphoma; cutaneous B-cell lymphomas Am J Surg Pathol 10:454–463, 1986; diffuse large cell B-cell lymphoma – acute violaceous indurated plaque of neck Ped Derm 34:703–705, 2017; angiocentric lymphoma – edema of face and neck Indian J Pathol Microbiol 34:293–295, 1991; Hodgkin’s disease – ulcerated papules and nodules AD 133:1454–1455, 1457–1458, 1997; Hodgkin’s disease mimicking scrofuloderma Dermatology 199:268–270, 1999; granulomatous slack skin syndrome (CTCL) BJD 142:353–357, 2000; Ped Derm 14:204–208, 1997; AD 121:250–252, 1985; lymphomatous lymphadenopathy – neck masses Ped Clin North Amer 6:1151–1160, 1993; Burkitt’s lymphoma CD4+ small,/medium pleomorphic T-cell lymphoma – skin colored nodule of face, red nodule of scalp, red plaque of neck JAAD 65:739–748, 2011; primary cutaneous follicle center cell lymphoma – multilobulated nodules, red plaques of scalp, nodules of head and neck, papules of head and neck JAAD 70:1010–1020, 2014; subcutaneous panniculitis-like T-cell lymphoma – nodules of head and neck, legs, trunk, cheeks, lips Ped Derm 32:526–532, 2015 angioimmunoblastic T-cell lymphoma – red plaque of neck Cutis 102:179–182, 2018; CD4/CD8

Nuchal fibroma – solitary subcutaneous mass of back of neck; multiple lesions associated with Gardner’s syndrome JAAD 66:959–965, 2012 Paraganglioma – neck mass Ped Clin NA 6:1151–1160, 1993; Pilomatrixoma Am J Dermatopathol 41:293–295, 2019; Clin Exp Dermatol 42:400–402, 2017; Otolaryngol Head Neck Surg 125:510–515, 2001; J Cutan Pathol 18:20–27, 1991 Porokeratosis – personal observation Post-transplantation lymphoproliferative disorder – lymphadenopathy of head and neck JAAD 54:657–663, 2006 Primary histiocytic sarcoma Ann Diag Pathol 32:56–62, 2018 Rhabdomyosarcoma – neck nodule in children JAAD 31:871–876, 1994; Ped Clin North Amer 6:1151–1160, 1993 Schwannoma – supraclavicular mass Head and Neck 21:239–246, 1999; lateral neck nodule Ped Derm 353–354, 2016 Spinal cord tumor – excoriations – personal observation Spindle cell lipoma – subcutaneous nodule of posterior neck AD 142:921–926, 2006 Squamous cell carcinoma J Laryngol Otol 110:694–695, 1996; metastatic squamous cell carcinoma – red nodule of submandibular region J Drugs Dermatol 13:1277–1279, 2014; Marjolin’s ulcer Exp Ther Med 17:3403–3410, 2019 Syringocystadenoma papilliferum AD 121:1198–1201, 1985; linear vascular appearing nodules of neck AD 144:1509–1514, 2008 Syringoma – generalized eruptive Dermatol Online J Sept 15, 2017 Syringomatous carcinoma – neck plaque Cutis 77:19–24, 2006 Thymus gland rests – mass of lower neck or suprasternal notch Ped Clin NA 6:1151–1160, 1993

678 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Thyroid adenoma, carcinoma, colloid cysts – neck nodules Ped Clin NA 6:1151–1160, 1993 Trichilemmal carcinoma Saudi Med J 39:213–216, 2018

Disseminate and recurrent infundibulofolliculitis – skin-colored papules and pustules of neck and upper chest Indian J Dermatol 64:404–406, 2019

Trichoblastic carcinoma Arch Craniofac Surg 19:275–278, 2018

Dowling-Degos disease

Trichoepithelioma Acta DV Croat 26:162–165, 2018; unilateral trichoepitheliomas of neck Dermatol Online J Nov 18, 2015

Elastoderma JAAD 53:S147–149, 2005

Tumor of follicular infundibulum – facial and neck hypopigmented macules and patches (multiple) JAMADerm 152:1155–1156, 2016 Verrucous carcinoma Warthin’s tumor, extraparotid – skin colored neck nodule JAAD 40:468–470, 1999 Warty dyskeratoma

Elastosis perforans serpiginosa J Dermatol 24:458–465, 1997; Hautarzt 43:640–644, 1992; AD 97:381–393, 1968 Epidermodysplasia verruciformis – personal observation Epidermolysis bullosa – epidermolysis bullosa simplex – neck bullae BJD 162:980–989, 2010; recessive inverse dystrophic – groin, axillae, neck, lower back, nail dystrophy, oral erosions (dermolytic dystrophic) AD 124:544–547, 1988 Epidermolytic hyperkeratosis Erythema annulare centrifugum

PARANEOPLASTIC DISORDERS Acrokeratosis paraneoplastica (Bazex syndrome) J Laryg Otol 110:899–900, 1996 Necrobiotic xanthogranuloma with paraproteinemia Case Rep Dermatol 8:350–353, 2016; Int J Clin Exp Pathol 8:3304–3307, 2015 Normolipemic plane xanthomatosis BJD 135:460–462, 1996

PHOTODERMATOSES Actinic granuloma AD 122:43–47, 1986 Berloque dermatitis Cutis rhomboidalis nuchae Photoallergic contact dermatitis – personal observation

Erythromelanosis follicularis of face and neck (faciei et colli) – redbrown pigmentation with telangiectasias, follicular papules involving preauricular and maxillary regions and extending to mandible and neck Cutis 79:459–461, 2007; Ped Derm 23:31–34, 2006; JAAD 32:863–866, 1995; Hautarzt 9:391–393, 1960 Fibroelastolytic papulosis of the neck BJD 173:461–466, 1997 Granular parakeratosis – red neck Ped Derm 33:665–666, 2016 Granuloma annulare Citos 55:158–160, 1995 Granuloma gluteal infantum – personal observation Grover’s disease (benign papular acantholytic dermatosis) AD 112:814–821, 1976 Hailey-Hailey disease Open Acesi Maced J Med Sci 7:3070–3072, 2019; BJD 126:275–282, 1992; Arch Dermatol Syphilol 39:679–685, 1939

Phytophotodermatitis – personal observation

Neonatal ichthyosiform erythroderma, hyperpigmented verrucous and cerebriform plaques of heels and neck BJD 176:249–251, 2017

Poikiloderma of Civatte Ann Dermatol Syphilol 9:381–420, 1938

Ichthyosis vulgaris – personal observation

Riehl’s melanosis

Idiopathic eruptive macular hyperpigmentation – light brown non-confluent macules 3–25 mm of neck or extremities (distinguished from erythema dyschromicum perstans) BJD 157:840-, 2007; JAAD 49:S280–282, 2003; JAAD 44: 351–353, 2001; Ped Derm 13:274–277, 1996; JAAD 11:159, 1984; Ann DV 105:177– 182, 1978

PRIMARY CUTANEOUS DISORDERS Acanthosis nigricans/pseudoacanthosis nigricans Acne keloidalis nuchae Plast Reconstr Surg Glob Open 7:e2215, 2019 Acne vulgaris AD 131:341–344, 1995 Alopecia mucinosa (follicular mucinosis) – neck plaque JAAD 38:622–624, 1998; Dermatology 197:178–180, 1998; JAAD 10:760–768, 1984; AD 76:419–426, 1957 Atopic dermatitis Anetoderma of Jadassohn AD 120:1032–1039, 1984 Annular lichenoid dermatitis of youth Dermatol Ther 27:e13285, 2020

Impetigo herpetiformis Juxtaclavicular beaded lines J Cutan Pathol 18:464–468, 1991 Kimura’s disease Exp Ther Med 16:1087–1093, 2018; Am J Kid Dis 11:353–356, 1988 Lichen nitidus Lichen planus including lichen planus pigmentosus Clin Exp Dermatol 44:190–193, 2019 Lichen sclerosus et atrophicus, guttate Lichen simplex chronicus

Blaschkitis – personal observation

Lichen spinulosus JAAD 22:261–264, 1990

Bullous prurigo pigmentosa – pruritic reticulated bullous eruption of neck and trunk JAMADerm 150:1005–1006, 2014; Dermatologica sinica 27:103–110, 2009

Lupus miliaris disseminate faciei Am J Dermatopathol 40:819–823, 2018

Centrifugal lipodystrophy Dermatology 188:142–144, 1994

Napkin psoriasis

Confluent and reticulated papillomatosis Actas Dermatosifiliogr 109:e7–911, 2018

Nevoid hypertrichosis

Cutis laxa

Pityriasis rubra pilaris – personal observation

Darier’s disease Dermatology 188:157–159, 1994

Prurigo nodularis

Diaper dermatitis with rapid dissemination – expanding nummular dermatitis of trunk, and red scaly plaques of neck and axillae (“psoriasiform id”) BJD 78:289–296, 1966

Prurigo pigmentosa – red papules with vesiculation and crusting arranged in reticulated pattern or reticulate plaques of back, neck, and chest; heals with reticulated hyperpigmentation; urticarial red

Miliaria rubra in infants BJD 99:117–137, 1978

Pityriasis rosea

Neck Lesions pruritic papules, papulovesicles, vesicles, and plaques with reticulated hyperpigmentation Ped Derm 24:277–279, 2007; JAAD 55:131–136, 2006; Cutis 63:99–102, 1999; JAAD 34:509–11, 1996; AD 130:507–12, 1994; BJD 120:705–708, 1989; AD 125:1551– 1554, 1989; JAAD 12:165–169, 1985; J Dermatol 5:61–67, 1978; Jpn J Dermatol 81:78–91, 1971 Pseudofolliculitis barbae Psoriasis Scleredema of Buschke (pseudoscleroderma) JAAD 11:128–134, 1984 Seborrhiasis Syringolymphoid hyperplasia JAAD 49:1177–1180, 2003 Terra firme (Diogenes syndrome) (terra firme-forme dermatosis) – hyperpigmented hyperkeratotic plaques of neck of teenagers and pre-teens (teenage scruff neck) Ped Derm 36:501–504, 2019; Ped Derm 29:297–300, 2012; self-neglect Lancet i:366–368, 1975 Upper dermal elastolysis J Cutan Pathol 21:533–540, 1994 Vitiligo White fibrous papulosis of the neck Int J Derm 35:720–722, 1996; BJD 127:295–296, 1992 X-linked ichthyosis

PSYCHOCUTANEOUS DISEASES Factitial dermatitis Ann DV 143:210–214, 2016; Ped Derm 32:604– 608, 2015

SYNDROMES Acrogeria Dermatology 192:264–268, 1996 Aicardi syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.292–293 Albright’s hereditary osteodystrophy – pseudohypoparathyroidism, round face, short neck, osteomas of skin with overlying hyperpigmentation, short stature, hypogonadism, macrocephaly, psychomotor retardation, endocrinologic abnormalities; mutation in GNAS1 JAMA Derm 149:975–976, 2013; Ped Derm 28:135–137, 2011; Endocrinology 30:922–932, 1942 Barber-Say syndrome – generalized hypertrichosis, dysmorphic facies (bilateral ectropion, hypertelorism, macrostomia, abnormal ears, bulbous nose, sparse eyebrows and eyelashes, hypoplasia of nipples with absence of mammary glands, transposition of scrotum, club feet, short neck, lax skin, premature aged appearance, cleft palate, conductive hearing loss Ped Derm 23:183–184, 2006; Syndrome Ident 8:6–9, 1982

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microphthalmia, coloboma, nasolacrimal duct stenosis or atresia, dolichocephaly; mutation in TFAP2A (retinoic acid responsive gene) Ped Derm 29:759–761, 2012; Mol Vis 16:813–818, 2010; Arch Otolaryngol Head Neck Surg 128:714–717, 2002; (pseudocleft of upper lip, cleft-lip-palate, and hemangiomatous branchial cleft) – atrophic neck lesions Ped Derm 29:383–384, 2012; Am J Med Genet 27:943–951, 1987 Branchio-oto-renal syndrome (Melnick-Fraser syndrome) – autosomal dominant, chromosome 8q – abnormal pinna, prehelical pits, renal anomalies, branchial cleft fistulae and/or cysts pre-auricular sinus tract or cyst Am J Nephrol2:144–146, 1982; Am J Med Genet 2:241–252, 1978; Clin Genet 9:23–34, 1976 Brooke-Spiegler syndrome – eccrine spiradenomas, cylindromas, trichoepitheliomas Int J Surg Case Rep 51:277–281, 2018 Buschke-Ollendorff syndrome Eur J Dermatol 11:576–579, 2001 Cleidocranial dysplasia Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.32–33 Coffin-Siris syndrome – webbed neck, bifid scrotum, umbilical and inguinal hernias JAAD 46:161–183, 2002 Cornelia de Lange (Brachmann-de Lange) syndrome – generalized hypertrichosis, and hypertrichosis of posterior neck, confluent eyebrows, low hairline, hairy forehead and ears, hair whorls of trunk, single palmar crease, cutis marmorata, psychomotor and growth retardation with short stature, specific facies, hypertrichosis of forehead, face, back, shoulders, and extremities, bushy arched eyebrows with synophrys; long delicate eyelashes, skin around eyes and nose with bluish tinge, small nose with depressed root, prominent philtrum, thin upper lip with crescent shaped mouth, widely spaced, sparse teeth, hypertrichosis of forehead, and arms, low set ears, arched palate, antimongoloid palpebrae; congenital eyelashes Ped Derm 24:421–423, 2007; JAAD 37:295–297, 1997; Am J Med Genet 47:959–964, 1993 Costello syndrome – warty papules around nose and mouth, legs, perianal skin; loose skin of neck, hands, and feet, thick, redundant palmoplantar surfaces, hypoplastic nails, short stature, craniofacial abnormalities Am J Med Genet 117:42–48, 2003; Eur J Dermatol 11:453–457, 2001; Am J Med Genet 82:187–193, 1999; JAAD 32:904–907, 1995; Am J Med Genet 47:176–183, 1993; Aust Paediat J 13:114–118, 1977 Cowden’s syndrome – skin tags OSOMOPOR 125:209–214, 2018 Craniocarpotarsal dysplasia (whistling face syndrome) – webbed neck Birth Defects 11:161–168, 1975 Delleman syndrome (oculocerebrocutaneous syndrome) – pedunculated facial papules and atrophic patches of neck; accessory tragi and aplasia cutis congenita AD 147:345–350, 2011; J Med Genet 25:773–778, 1988

Baverstedt syndrome – linear horny excrescences of face and neck; mental retardation, seizures Acta DV 22:207–212, 1941

Diffuse infiltrative lymphocytosis syndrome (DILS) – autoimmune syndrome with oligoclonal expansion of CD8+ T lymphocytes in response to HIV antigens; lymphocytic infiltration of salivary glands (parotid glands) and viscera Clin Lab Haem 27:278–282, 2005

Becker’s syndrome – discrete or confluent brown macules of neck, forearms AD Syphilol 40:987–998, 1939

Diffuse pigmentation of trunk and neck with subsequent white macules Proc R Soc Med 48:179–180, 1955

Behcet’s syndrome – superior vena cava syndrome – superior and inferior vena cava obstruction; dilated and tortuous veins of chest wall, facial edema, thickening of neck with neck vein distension, upper body edema and edema of arms and legs, proptosis; superficial and deep thrombophlebitis BJD 159:555–560, 2008

Diffuse pigmentation with macular depigmentation of trunk with reticulate pigmentation of neck Hautarzt 6:458–460, 1955

Birt-Hogg-Dube syndrome AD 133:1163–1166, 1997; comedonal or cystic fibrofolliculomas JAMADerm 151:770–774, 2015 Branchiooculofacial syndrome – autosomal dominant; congenital bilateral cervical ulcerations (bilateral ectopic thymus glands); congenital ulcerated neck mass (ectopic thymus), flattened nasal tip, pseudo-cleft lip, posterior rotated ears, pre-auricular pit, cleft lip,

Distichiasis and lymphedema – webbed neck Dowling-Degos disease Indian J DV Leprol 84:70–72, 2018 Down’s syndrome – webbed neck Dyskeratosis congenita (Zinsser-Engman-Cole syndrome) – Xq28 J Med Genet 33:993–995, 1996; Dermatol Clin 13:33–39, 1995; BJD 105:321–325, 1981 Ekbom’s syndrome (myoclonic epilepsy and ragged muscle fibers) (mitochondrial syndrome) – cervical lipomas JAAD 39:819–823, 1998

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Encephalocraniocutaneous lipomatosis Ped Derm 10:164–168, 1993

Mobius sequence Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.492–493

Epidermodysplasia verruciformis Franceschetti-Jadassohn-Naegeli syndrome – generalized reticulated hyperpigmentation, accentuated in neck and axillae JAAD 10:1–16, 1984

Morquio syndrome (mucopolysaccharidosis type IV) – autosomal recessive; short neck, skeletal abnormalities, corneal clouding, cardiac valvulopathies, odontoid hypoplasia, hypermobile joints Ped Derm 33:594–601, 2016

Gardner’s syndrome – nuchal-type fibroma Am J Surg Pathol 24:1563–1567, 2000

Mottled pigmentation of neck and elbows Z Haut-u Geschl Krankh 32:33–44, 1962

Goldenhar syndrome (oculoauriculovertebral syndrome) – epibulbar dermoid cysts, vertebral defects, accessory tragi Int J Derm 19:479–486, 1980

Multiple endocrine neoplasia syndrome type II – medullary carcinoma of the thyroid Ped Clin North Amer 6:1151–1160, 1993

Hermansky-Pudlak syndrome – actinic keratoses J Dermatol 44:219–220, 2017 Hidrotic ectodermal dysplasia Hautarzt 42:645–647, 1991 Hunter’s syndrome – skin colored to white papules of nape of neck AD 113:602–605, 1977 Infantile cortical hyperostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.102–103 Infantile myofibromatosis Int J Pediatr Otorhinolaryngol 51:181–186, 1999; Ped Derm 8:306–309, 1991; Ped Derm 5:37–46, 1988 Job’s syndrome (hyper IgE syndrome) – autosomal dominant or sporadic; cold abscesses of neck and trunk; atrophoderma vermiculatum; coarse facial features with broad nose, rough thickened skin with prominent follicular ostia; papular and papulopustular folliculitis-like eruptions; oral candidiasis; chronic paronychia; otitis media common; mutation in STAT3 (transcription 3 gene activator and signal transducer) JAAD 65:1167–1172, 2011 Juvenile hyaline fibromatosis (systemic hyalinosis) – translucent papules or nodules of scalp, face, neck, trunk, gingival hypertrophy, flexion contractures of large and small joints JAAD 16:881–883, 1987 Kawasaki’s disease – cervical adenopathy Ped Clin North Amer 6:1151–1160, 1993 Klippel-Feil anomaly – webbed neck J Bone Jt Surg 56:1246–1253, 1974; neckless or short neck Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.296–297 LEOPARD (Moynahan) syndrome – CALMs, granular cell myoblastomas, steatocystoma multiplex, small penis, hyperelastic skin, low set ears, short webbed neck, short stature, syndactyly JAAD 46:161–183, 2002; Am J Med 60:447–456, 1976; JAAD 40:877– 890, 1999; J Dermatol 25:341–343, 1998; Am J Med 60:447–456, 1976; AD 107:259–261, 1973 Lymphedema-distichiasis syndrome – periorbital edema, vertebral abnormalities, spinal arachnoid cysts, congenital heart disease, thoracic duct abnormalities, hemangiomas, cleft palate, microphthalmia, strabismus, ptosis, short stature, webbed neck Ped Derm 19:139–141, 2002; Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.460–461 Madelung’s deformity McCune-Albright syndrome – café au lait macule Ped Derm 8:35–39, 1991 Menkes’ kinky hair syndrome – silvery hair, generalized hypopigmentation, lax skin of brows, neck, and thighs Ped Derm 15:137– 139, 1998 Microphthalmia with linear skin defects syndrome (MLS syndrome) (microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome) – X-linked dominant; atrophic Blaschko linear scars of face and neck; linear red atrophic skin (resembles aplasia cutis) Ped Derm 37:217–218, 2020; Am J Med Genet 49:229–234, 1994

Multiple pterygium syndrome – webbed neck J Med Genet 24:733–749, 1987 Neu-Laxova syndrome – short neck; mild scaling to harlequin ichthyosis appearance; ichthyosiform scaling, increased subcutaneous fat and atrophic musculature, generalized edema and mildly edematous feet and hands, absent nails; microcephaly, intrauterine growth retardation, limb contractures, low set ears, sloping forehead; small genitalia, eyelid and lip closures, syndactyly, cleft lip and palate, micrognathia; autosomal recessive; uniformly fatal Ped Derm 20:25–27,78–80, 2003; Curr Prob Derm 14:71–116, 2002; Clin Dysmorphol 6:323–328, 1997; Am J Med Genet 35:55–59, 1990 Neurofibromatosis – type I; segmental neurofibromatosis J La State Med Soc 146:183–186, 1994; plexiform neurofibroma NEJM 382:1430–1442, 2020 Noonan’s syndrome – malformed ears, nevi, keloids, transient lymphedema, ulerythema ophryogenes, keratosis follicularis spinulosa decalvans, joint hyperextensibility, hypertelorism, webbed neck, down slanting of palpebral fissures, keratosis pilaris atrophicans, short stature, chest deformity (pectus carinatum and pectus excavatum), cubitus valgus, radioulnar synostosis, clinobrachydactyly, congenital heart disease; PTPN 11 gene on chromosome 12; SOS1, RAF1, gain of function of non-receptor protein tyrosine phosphate SHP-2 or KRAS gene Ped Derm 24:417–418, 2007; JAAD 46:161– 183, 2002; J Med Genet 24:9–13, 1987; J Pediatr 63:468–470, 1963 Occipital horn syndrome (Ehlers-Danlos syndrome, type IX) – long neck Am J Hum Genet 41:A49, 1987 Oculo-auricular vertebral syndrome – short neck, epibulbar dermoid tumors, abnormal hair Ped Derm 20:182–184, 2003 Pallister-Killian syndrome – short neck; streaks of hypo- and hyperpigmentation, mental retardation, coarse facies with prominent forehead with abnormally high anterior hairline, sparse temporal hair and sparse anterior scalp hair, hypertelorism, short nose with anteverted nostrils, flat nasal bridge, flat occiput, sparse eyelashes, long philtrum with thin upper lip, horizontal palpebral fissure, supernumerary nipples, Blaschko linear hypopigmented bands of face and shoulder; i(12p) (tetrasomy 12p); tissue mosaicism; pigmentary mosaicism and localized alopecia Ped Derm 24:426–428, 2007; Ped Derm 23:382–385, 2006; Ped Derm 22:270–275, 2005 PAPA (pyogenic arthritis, pyoderma gangrenosum, acne vulgaris) syndrome – autosomal dominant; mutation in proline serine threonine phosphatase-interacting protein 1 (PSTPIP1) BJD 161:1199–1201, 2009; Mayo Clin Proc 72:611–615, 1997 Patau’s syndrome (trisomy 13) – loose skin of posterior neck, parieto-occipital scalp defects, abnormal helices, low set ears, simian crease of hand, hyperconvex narrow nails, polydactyly Ped Derm 22:270–275, 2005 Phakomatosis pigmentovascularis J Dermatol 46:843–848, 2019 Poland anomaly Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.390–391 Proteus syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.352–355

Neck Lesions

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Pseudoxanthoma elasticum – linear and reticulated cobblestoned yellow papules and plaques AD 124:1559, 1988; JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; PXE and acrosclerosis Proc Roy Soc Med 70:567–570, 1977

Fiddler’s neck – lichenification with erythema, hyperpigmentation, papules, pustules, and cysts BJD 98:669–674, 1978

Pterygium colli medianum Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.58–59

Hickey (passion mark)

Rigid spine syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.446

Strangulation purpura

SAPPHO syndrome Oral Radiol Aug 14, 2019 Short stature, mental retardation, facial dysmorphism, short webbed neck, skin changes, congenital heart disease – xerosis, dermatitis, low set ears, umbilical hernia Clin Dysmorphol 5:321–327, 1996 Sjogren-Larsson syndrome – verrucous hyperkeratosis of flexures, neck, and periumbilical folds; mental retardation, spastic diplegia, short stature, kyphoscoliosis, retinal changes, yellow pigmentation, intertrigo – deficiency of fatty aldehyde dehydrogenase Chem Biol Interact 130–132:297–307, 2001; Am J Hum Genet 65:1547–1560, 1999; JAAD 35:678–684, 1996 Spondylocostal dysostosis Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.294–295 Steatocystoma multiplex Sweet’s syndrome – red plaque with or without bullae or pustules red plaque NEJM 382:1543, 2020; JAAD 69:557–564, 2013; JAAD 40:838–841, 1999; AD 134:625–630, 1998; Eur J Gastro Heptl 9:715–720, 1997; JAAD 31:535–536, 1994; BJD 76:349–356, 1964 Thrombocytopenia-absent radius syndrome (TAR syndrome) – cutis laxa of neck; congenital thrombocytopenia, bilateral absent or hypoplastic radii, port wine stain of head and neck AD 126:1520– 1521, 1990; Am J Pediatr Hematol Oncol 10:51–64, 1988 Trisomy 13 (Patau syndrome) – redundant skin of neck J Genet Hum 23:83–109, 1975 Trisomy 18 syndrome – redundant skin of neck J Med Genet 15:48–60, 1978 Tuberous sclerosis – fibrous cephalic plaque of neck JAAD 78:717–724, 2018; Head Neck Pathol 542–546, 2016 Turner’s syndrome (XO in 50%) – webbed neck, lymphedema of neck; low posterior hairline, low misshapen ears, peripheral edema at birth which resolves by age 2; redundant neck skin in newborn; small stature, broad shield-shaped chest with widely spaced nipples, arms show wide carrying angle, high arched palate, cutis laxa of neck and buttocks, short fourth and fifth metacarpals and metatarsals, hypoplastic nails, keloid formation, increased numbers of nevi; skeletal, cardiovascular, ocular abnormalities; increased pituitary gonadotropins with low estrogen levels JAAD 50:767–776, 2004; JAAD 46:161–183, 2002; JAAD 40:877–890, 1999; NEJM 335:1749– 1754, 1996; halo nevi of the neck JAAD 51:354–358, 2004 Weaver-Williams syndrome (cleft palate, microcephaly, mental retardation, musculoskeletal mass deficiency) – long neck Birth Defects 13:69–84, 1977 Wildervanck syndrome Atlas of Clinical Syndromes A Visual Aid to Diagnosis, 1992, pp.298–299 49,XXXXY syndrome – webbed neck Syndromes of the Head and Neck, p. 59–60, 1990

TRAUMA Chemical leukoderma – from dimethyl sulfate An Bras Dermatol 91(suppl 1)26–28, 2016 Dental treatment – soft tissue cervicofacial emphysema after dental treatment AD 141:1437–1440, 2005

Frostbite – bullous frostbite in a snowmobiler (Polaris vulgaris) Cutis 63:21–23, 1999 Neck impalement with tree branch NEJM 373:366, 2015 Subcutaneous emphysema AD 134:557–559, 1998 Thermal burn

VASCULAR DISORDERS Acquired elastotic hemangioma – red plaque with vascular appearance JAAD 47:371–376, 2002 Acquired port wine stain – red patches of neck, upper back, lower leg, posterior thigh Ped Derm 37:93–97, 2020 Aneurysmal dilatation of the internal jugular vein – soft blue neck mass Ped Clin North Amer 6:1151–1160, 1993 Angiolymphoid hyperplasia with eosinophilia Actas Dermosifiliogr 110:303–307, 2019; Dermatol Online J Dec 16, 2015 Angiosarcoma BJD 138:692–694, 1998; Australas Radiol 39:277– 281, 1995; Cancer 44:1106–1113, 1979 Angioma serpiginosum Arteriovenous fistulae – congenital or acquired; red pulsating nodules with overlying telangiectasia – extremities, head, neck, trunk Blue rubber bleb nevus syndrome World J Gastroenterol 20:17254– 17259, 2014 CLAPO syndrome – capillary malformation of lower lip; lymphatic malformation of face and neck; swollen lip, prominent veins of neck, jaw and scalp, asymmetry of face and limbs, partial or generalized overgrowth reticulate erythema of neck; PIK3CA mutation Ped Derm 35:681–682, 2018 Dabska tumor (malignant endovascular papillary endothelioma) – head and neck of infants JAAD 49:887–896, 2003 Granulomatosis with polyangiitis – ulcer of posterior neck JAMADerm 152:1375–1376, 2016; pyoderma gangrenosum-like ulcers of neck in teenage boy Tidsskr Nor Laegeforen April 8, 2019 Hemangioma – symptomatic hemangiomas of the airway with airway obstruction and cutaneous hemangiomas in a “beard” distribution J Pediatr 131:643–646, 1997; large neck mass; hemangioma beyond proliferative stage – hypertrophy of lip, chin, and neck Ped Derm 28:94–98, 2011 Non-involuting congenital hemangioma JAAD 53:185–186, 2005 Kaposiform hemangioendothelioma Ann Diagn Pathol 44:151434, 2020 Lymphatic malformation Port wine stain JAAD 80:779–781, 2019 Pseudo-Kaposi’s sarcoma Pyogenic granuloma – head and neck most common affected sites Tokol J Exp Clin Med 20:110–114, 2015 Salmon patch (nevus simplex) (“stork bite”) – pink macules with fine telangiectasias of the nape of the neck, glabella, forehead, upper eyelids, tip of nose, upper lip, midline lumbosacral area Ped Derm 73:31–33, 1983 Thoracic duct obstruction – non-inflammatory swelling of supraclavicular fossa – obstruction of cervical portion of thoracic duct AD 147:1337–1338, 2011; Vasc Med 9:141–143, 2004; Lymphology 28:118–125, 1995

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Tufted angioma – dull red, purple, or red-brown JAAD 49:887–896, 2003; Ped Derm 19:388–393, 2002; vascular nodule Ped Derm 29:778, 2012

Syndromes of the Head and Neck; Oxford Monographs on Medical Genetics No. 19; Oxford University Press; Oxford/New York; 1990

Unilateral nevoid telangiectasia

Ectopic or christomatous salivary gland (heterotopic salivary gland tissue) – skin colored nodule along lower surface of the sternocleidomastoid muscle JAAD 58:251–256, 2008

Venous lakes

Glandular congenital lymphadenoma Ped Derm 24:547–550, 2007

NECK PAPULES

Midline cervical cleft Int J Pediatr 2015:209418, 2015

 UTOIMMUNE DISEASES OR DISEASES A OF IMMUNE DYSFUNCTION

Rhabdomyomatous mesenchymal hamartoma – pedunculated papule associated with a midline cervical cleft AD 141:1161–1166, 2005

Dermatitis herpetiformis AD 147:1313–1316, 2011

Supernumerary nipples Cutis 71:344–346, 2003

DOCK8 deficiency syndrome (dedicator of cytokinesis 8 gene) (aka autosomal recessive hyper-IgE syndrome) DOCK8 – involved in T cell polarization and activation; atypical guanine exchange factor; interacts with Rho GTPases (CDC42 AND RAC) which mediate actin cytoskeletal reorganization; hematologic stem cell homing and mobilization – immunodeficiency; resembles Job’s syndrome; decrease T and B cells; increased IgE, decreased IgM, increased eosinophilia; recurrent sinopulmonary infections, severe cutaneous viral infections and lymphopenia; red papules of neck – molluscum contagiosum; warts, widespread dermatitis (atopic dermatitis-like) (24% at birth; Job’s 81% dermatitis at birth), asthma, cutaneous staphylococcal abscesses; malignancies – aggressive T-cell lymphoma vulvar squamous cell carcinoma, diffuse large B-cell lymphoma; Job’s syndrome may be differentiated by presence of pneumatoceles and bronchiectasis, rash at birth, osteoporosis, scoliosis, craniosynostosis, minimal trauma fractures, joint hyperextensibility; dominant negative STAT3 mutation AD 148:79–84, 2012

Thyroglossal duct cyst Semin Pediatr Surg 15:70–75, 2006

Occult spinal dysraphism Ped Derm 12:256–259, 1995

DRUG REACTIONS Atorvastatin-induced dermatomyositis Rheumatol Int 37:1217–1219, 2017 Cyclosporine – pseudofolliculitis barbae-like lesions Dermatologica 172:24–30, 1986

EXOGENOUS AGENTS Chrysiasis BJD 133:671–678, 1995 Fiberglass dermatitis Kao Hsiung J Med Sci 12:491–494, 1996 Silica granulomas from mine explosion – red nodules of face, neck, chest JAMADerm 154:953–954, 2018

Graft vs. host reaction, acute Taiwan I Hsueh Hui Tsa Chih 88:657–662, 1989 IgG4-related disease Mod Rheumatol 23:986–993, 2013

INFECTIONS AND INFESTATIONS

Lupus erythematosus – papulonodular mucinosis; papules of neck JAAD 32:199–205, 1995; AD 114:432–435, 1978

Bed bug bites Ped Derm 22:183–187, 2005

Still’s disease Semin Arthr Rheum 42:317–326, 2012

Candidiasis – Candida tropicalis sepsis, papillary muscle rupture – personal observation

Urticaria

CONGENITAL DISORDERS Accessory tragus – facial, glabellar papule – isolated, Treacher Collins syndrome (mandibulofacial dysostosis; autosomal dominant), Goldenhaar syndrome ((oculo-auriculo-vertebral syndrome) – macroglossia, preauricular tags, abnormal pinnae, facial asymmetry, macrostomia, epibulbar dermoids, facial weakness, central nervous system, renal, and skeletal anomalies), Nager syndrome, WolfHirschhorn syndrome (chromosome 4 deletion syndrome), oculocerebrocutaneous syndrome Ped Derm 17:391–394, 2000; Townes-Brocks syndrome Am J Med Genet 18:147–152, 1984; VACTERL syndrome J Pediatr 93:270–273, 1978 Branchial remnants – branchial cleft cyst/sinus Cutis 99:327–328, 2017; Plastic and Reconstructive Surgery 100:32–39, 1997

Botryomycosis Cutis 80:45–47, 2007

Cattle itch mite (Sarcoptes scabiei var. bovis) Hautarzt 30:423–426, 1979 Chromomycosis – feet, legs, arms, face, and neck AD 113:1027– 1032, 1997; BJD 96:454–458, 1977; AD 104:476–485, 1971 Coccidioidomycosis Acta Cytologica 38:422–426, 1994 Cryptococcosis AD 142:25–27, 2006 Demodicidosis – erythema and papules of neck (demodex folliculitis) Cutis 90:62,65–66, 2012; J Med Assoc Thai 74:116–119, 1991 Dental sinus – neck nodule Ped Derm 29:421–425, 2012; Am Fam Physician 40:113–116, 1989 Histoplasmosis – disseminated histoplasmosis in AIDS; red papules of neck AD 143:255–260, 2007 HTLV III JAAD 13:563–566, 1985

Cervical braid Brit J Plast Surg 43:369–370, 1990

Leishmania ID Cases 18:60–62, 2014

Congenital malalignment of the great toenails Dermatol Surg 45:1211–1213, 2019; Clin Exp Dermatol 8:619–623, 1983; Clin Exp Dermatol 4:309–313, 1979

Molluscum contagiosum Ann Dermatol 25:398–399, 2013

Congenital onychodysplasia of the index finger Genetic Skin Disorders, Second Edition, 2010, pp.244 Congenital paramedian canaliform dystrophy – personal observation Cutaneous cartilaginous rest (cervical accessory auricle (wattle)) AD 121:22–23, 1985; in oculo-auricular-vertebral spectrum

Mucormycosis – red nodule of neck Clin Inf dis 63:959,991–992, 2016 Mycobacterium tuberculosis – after BCG vaccination J Derm 21:106–110, 1924 Myiasis – cuterebrid myiasis; neck nodules Ped Derm 21:515–516, 2004 Nematode larvae JAAD 58:668–670, 2008

Neck Papules 683 Pediculosis – head lice – pruritic papules of nape of neck; generalized pruritic eruption NEJM 234:665–666, 1946

Kimura’s disease Am J Kidney disease 11:353–356, 1988

Pityrosporum folliculitis Mycoses 40(supp 1)29–32, 1997; Med Cut Ibero Lat Am 13:357–361, 1985

Necrotizing infundibular crystalline folliculitis – red umbilicated papules of face, neck, and back JAMA Derm 149:1233–1234, 2013; BJD 145:165–168, 2001; BJD 143:310–314, 1999

Protothecosis Mycopathologia 179:163–166, 2015

Neutrophilic eccrine hidradenitis SkinMed 15:297–299, 2017

Rickettsialpox – personal observation

Sarcoid JAAD 68:765–773, 2013; J Spec Oper Med 13:105–108, 2013; AD 133:882–888, 1997; NEJM 336:1224–1234, 1997; Clinics in Chest Medicine 18:663–679, 1997

Scabies JAAD 82:533–548, 2020; Ped Derm 11:264–266, 1994; neonatal scabies Am J Dis Child 133:1031–1034, 1979 Sporotrichosis – lateral neck nodules BJD 173:291–293, 2015 Staphylococcus aureus – folliculitis Sycosis barbae Tinea barbae – Trichophyton rubra, Majocchi’s granuloma Mycopathologia 182:549–554, 2017 Verruca vulgaris Verruga peruana Am J Trop Med and Hygiene 50:143, 1994

INFILTRATIVE DISORDERS Angioplasmocellular hyperplasia – red nodule with red rim, ulcerated nodule, vascular nodule of face, scalp, neck, trunk, and leg JAAD 64:542–547, 2011 Benign cephalic histiocytosis – cheeks, forehead, earlobes, neck JAAD 47:908–913, 2002; Ped Derm 11:265–267, 1994; Ped Derm 6:198–201, 1989; AD 122:1038–43, 1986; JAAD 13:383–404, 1985

METABOLIC DISEASES Cryoglobulinemia JAAD 25:21–27, 1991 Pruritic urticarial papules and plaques of pregnancy (PUPPP) Z Hautkr 65:831–832, 1990 Xanthomas, eruptive Acta Med Port 30:219–222, 2018

NEOPLASTIC DISORDERS Acrochordon (skin tag) Adenoid cystic carcinoma JAAD 17:113–118, 1987 Adenosquamous carcinoma of the skin – red keratotic papule or plaque of head, neck or shoulder; extensive local invasion AD 145:1152–1158, 2009 Angiosarcoma BJD 138:692–694, 1998

Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease) Ped Derm 23:273–275, 2006; JAAD 48:S75–77, 2003

Apocrine adenoma – personal observation

Primary and secondary intralymphatic histiocytosis – red papule or nodule of neck J Dermatol 35:691–693, 2008;; red patch of back; livedo reticularis JAAD 70:927–933, 2014

Apocrine hidrocystoma Stat Pearls Dec 23, 2019

Apocrine carcinoma Cancer 71:375–381, 1993

Indeterminate cell histiocytosis Am J Dermatopathol 19:276–283, 1997

Atypical fibroxanthoma Semin Cut Med Surg 38:E65–66, 2019; Dermatol Surg 37:146–147, 2011; AD 146:1399–1404, 2010; Sem Cut Med Surg 21:159–165, 2002; Cutis 51:47–48, 1993; Cancer 31:1541–1552, 1973; crusted pink papule of neck Ped Derm 24:450–452, 2007

Juvenile xanthogranuloma Ped Derm 26:238–240, 2009; Ped Derm 15:65–67, 1998

Basal cell carcinoma AD 126:102,104–105, 1990; Acta Pathol Microbiol Scand 88A:5–9, 1980

Lichen myxedematosus (scleromyxedema) JAAD 33:37–43, 1995; discrete papular lichen myxedematosus Cutis 75:105–112, 2005; Indian J DV Leprol 52:340–342, 1986

Benign cephalic histiocytomas Ped Derm 31:547–550, 2014; JAAD 47:908–913, 2002; Am J Dermatopathol 15:581–586, 1993

Follicular mucinosis Indian Dermatol Online J 4:333–335, 2013

Plane xanthomatosis BJD 133:961–966, 1995 Papular mucinosis – localized papular mucinosis associated with IgA nephropathy; cobblestoned shiny grouped follicular papules of the neck AD 147:599–602, 2011 Rosai-Dorfman disease Chin Med (Engl) 124:793–794, 2011

Eruptive blue nevi Cutis 102:E24–26, 2018; rare, often a triggering event is present Bowenoid papulosis – HPV 18 JAAD 40:633–634, 1999 Cardiac myxoma emboli J Dermatol 22:600–605, 1995 Cutaneous lymphadenoma – papules or nodules of head and neck BJD 128:339–341, 1993

Self-healing (papular) juvenile cutaneous mucinosis – yellow papules and plaques; arthralgias Ped Derm 32:e255–258, 2015; Ped Derm 20:35–39, 2003; JAAD 44:273–281, 2001; Ped Derm 14:460–462, 1997; AD 131:459–461, 1995; JAAD 11:327–332, 1984; Ann DV 107:51–57, 1980; of adult JAAD 50:121–123, 2004, BJD 143:650–651, 2000; Dermatology 192:268–270, 1996

Eruptive collagenoma J Dermatol 29:79–85, 2002; familial collagenoma Ann Dermatol 23:S119–122, 2011

Urticaria pigmentosa Pediatr Ann 43:e13–15, 2014

Dermal duct tumor – red nodule of neck AD 140:609–614, 2004

Xanthoma disseminatum J Postgrad Med 60:69–71, 2014

Dermatomyofibroma – oval nodule or firm plaque Ped Derm 34:347–351, 2017; Clin Exp Dermatol 21:307–309, 1996

Cylindromas BJD 151:1084–1086, 2004 Deep penetrating nevus – black or darkly pigmented nevus of head, neck, and scalp JAAD 71:1234–1240, 2014

Dermatosis papulosa nigra Stat Pearls April 30, 2020

INFLAMMATORY DISORDERS Eosinophilic pustular folliculitis J Dermatol 25:178–184 Erythema nodosum Folliculitis decalvans J Dermatol 28:329–331, 2001 Folliculitis nuchae scleroticans (acne keloidalis nuchae) Hautarzt 39:739–742, 1988

Desmoplastic trichoepithelioma AD 138:1091–1096, 2002; AD 132:1239–1240, 1996; Cancer 40:2979–2986, 1977 Encephalocraniocutaneous lipomatosis Ped Derm 10:164–168, 1993 Eruptive fibromas J Cutan Pathol 25:122–125 Eruptive histiocytoma J Dermatol 20:105–108, 1993 Eruptive lipofibromas AD 119:612–614, 1983

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Eruptive vellus hair cysts Fibrosarcoma, neonatal JAAD 50:S23–25, 2004

Neuroma – palisaded encapsulated neuroma AD 140:1003–1008, 2004

Fibrous hamartoma of infancy – neck nodule Ped Dev Pathol 2:236–243, 1999

Neurothekeoma An Bras Dermatol 90:156–159, 2015; J Drugs Dermatol 11:252–255, 2012; Am J Surg Pathol 14:113–120, 1990

Hamartoma moniliformis – linear array of skin-colored papules of face and neck AD 101:191–205, 1970

Nevus sebaceous Int J Dermatol 44:142–150, 2005

Infantile myofibromatosis – single or multiple; head, neck, trunk JAAD 41:508, 1999; AD 134:625–630, 1998 Inverted follicular keratosis J Clin Pathol 28:465–471, 1975 Kaposi’s sarcoma Ann Int Med 103:744–750, 1985 Keratoacanthomas of Ferguson-Smith – multiple self-healing keratoacanthomas JAAD 49:741–746, 2003; Ann DV 104:206–216, 1977; BJD 46:267–272, 1934; generalized eruptive keratoacanthomas Int J Dermatol 54:160–167, 2015 Leiomyomas – grouped, linear or dermatomal (Reed syndrome) The Dermatologist, July 2016, pp.47–49;JAAD 52:410–416, 2005; JAAD 46:477–490, 2002; piloleiomyomas Eur J Dermatol 9:309–310,1999 Leiomyosarcoma – blue-black; also red, brown, yellow or hypopigmented JAAD 46:477–490, 2002 Leukemia – chronic lymphocytic leukemia Laryngoscope 86:1856– 1863, 1976 Leukemid – personal observation Lymphoepithelioma-like carcinoma Mod Pathol 1:359–365, 1988 Lymphoma – CTCL; Ki-1+ lymphoma; Hodgkin’s disease AD 133:1454–1455, 1457–1458, 1997; B-cell lymphoma JAAD 53:479–484, 2005; xanthomatous infiltration of the neck Eur J Derm 10:481–483, 2000;; miliary and agminated primary follicle center lymphoma – multiple grouped papules of face, neck, trunk, and extremities JAAD 65:749–755, 2011; lymphoblastic lymphoma – red neck nodule JAAD 70:318–325, 2014; primary cutaneous follicle center cell lymphoma – multilobulated nodules, red plaques of scalp, nodules of head and neck, papules of head and neck JAAD 70:1010–1020, 2014; diffuse large cell B-cell lymphoma – multiple red subcutaneous nodules of neck BJD 173:134–145, 2015; post-transplant lymphoma JAAD 81:600–602, 2019 Lymphomatoid papulosis Acta DV Croat 26:264–266, 2018 Lymphoplasmocytoid immunocytoma Hautarzt 44:172–175, 1995 Melanocytic nevus – eruptive melanocytic nevi JAAD 37:337–339, 1997; J Dermatol 22:292–297, 1995 Melanoma, including metastatic melanoma – 2 mm brown papules of face and neck Ped Derm 27:201–203, 2010

Nuchal fibroma – solitary subcutaneous mass of back of neck; multiple lesions associated with Gardner’s syndrome JAAD 66:959–965, 2012 Palisaded encapsulated neuroma – benign nerve sheath proliferation; skin colored solitary papules of the head and neck in adults Am J Dermatopathol 41:358–360, 2019 Pilomatrixoma J Cutan Pathol 18:20–27, 1991 Pilomatrix carcinoma – multiple of head and neck Otolaryngol Head Neck Surg 109:543–547, 1993 Plasmacytoid dendritic cell neoplasm – purple macules, violaceous papules, nodules, tumefactions; highly pigmented dark red, purpuric, necrotic lesions of face, neck JAAD 66:278–291, 2012 Porokeratotic eccrine ostial and dermal duct nevus (linear eccrine nevus with comedones) AD 138:1309–1314, 2002 Primary cutaneous adenoid cystic carcinoma – violaceous nodules of face and neck JAAD 58:636–641, 2008 Cutaneous pseudolymphoma J Dermatol 32:594–601, 2005 Rhabdomyomatous mesenchymal hamartoma – ventral midline skin colored polypoid papule of neck Ped Derm 37:64–68, 2020; Ped Derm 33:449–450, 2016 Rhabdomyosarcoma JAAD 31:871–876, 1994 Sebaceous hyperplasias – linear neck papules; prepubescent sebaceous hyperplasias Ped Derm 28:198–200, 2011 Solitary fibrous tumor of the skin – facial, scalp, posterior neck nodule JAAD 46:S37–40, 2002 Squamous cell carcinoma Syringocystadenoma papilliferum AD 144:1509–1514, 2008; AD 138: 1091–1096, 2002; AD 121:1198–1201, 1985; linear verrucous papules AD 138:1091–1096, 2002 Syringomas, eruptive Dermatol Online J 2016 Aug 15; 22(8)13030qt4mm751qr; Cureus Nov 21, 2018 Tick bite – persistent atypical lymphocytic hyperplasia Ped Derm 18:481–484, 2001 Warty dyskeratoma – face, neck, scalp, axillae Iran J Public Health 43:1145–1147, 2014

Merkel cell carcinoma – pink to violaceous nodule Sem Cut Med Surg 21:159–165, 2002

PARANEOPLASTIC DISORDERS

Metastases – NUT (nuclear protein in testis) midline carcinoma JAAD 67:323–324, 2012; metastatic squamous cell carcinoma of the tongue NEJM 370:558, 2014; submandibular gland adenocarcinoma – personal observation; basaloid carcinoma of lung JAAD 49:523–526, 2003; renal cell carcinoma SkinMed 17:65–66, 2019; Australas J Dermatol 46:158–160, 2005; gastric adenocarcinoma Dermatol Reports 8:6819, 2017; salivary gland carcinoma Cutis 93:E16–18, 2014

Acrokeratosis paraneoplastica (Bazex syndrome) J Laryng Otol 110:899–900, 1996

Milia Acta Derm Venereol 71:334–336, 1991

PHOTODERMATOSES

Mucinous carcinoma JAAD 52:S76–80, 2005

Actinic granuloma (annular elastolytic giant cell granuloma) Dermatol Online J 18:23, 2012; AD 122:43–47, 1986

Multiple myeloma AD 139:475–486, 2003 Myofibroma J Cutan Pathol 23:445–457, 1996; Histopathol 22:335–341, 1993 Neurilemmoma (schwannoma) – pink-gray or yellowish nodules of head and neck Neurofibroma

Granulomatous rosacea-like leukemid in acute myelogenous leukemia Vojnosanit Pregl 65:565–568, 2008 Sweet’s syndrome Ear Nose Throat J 94:282–284, 2015; Clin Exp Rheumatol 27:588–590, 2009

PRIMARY CUTANEOUS DISORDERS Acantholytic dermatosis Nippon Hifuka Gakkai Zasshi 10:453–460, 1991

Neck Papules 685 Acne keloidalis JAAD 56:699–701, 2007; J Dermatol Surg Oncol 15:642–647, 1989

30:69–71, 2011; JAAD 51:958–964, 2004; Int J Derm 35:720–722, 1996; Ann DV 119:925–926, 1992; JAAD 20:1073–1077, 1989

Acne rosacea J Dermatol Case Rep 31:68–72, 2016 Acne vulgaris AD 131:341–344, 1995 Alopecia mucinosa (follicular mucinosis) – neck papules JAAD 38:622–624, 1998; Dermatology 197:178–180, 1998; JAAD 10:760–768, 1984; AD 76:419–426, 1957 Anetoderma of Jadassohn AD 120:1032–1039, 1984 Angiolymphoid hyperplasia with eosinophilia Stat Pearls April 23, 2020; Int J Dermatol 56:1373–1378, 2017; BJD 134:744–748, 1996 Atopic dermatitis Allergy Asthma Proc 40:433–436,2019 Benign papular acantholytic dermatosis AD 112:814–821, 1976 Confluent and reticulated papillomatosis of Gougerot and Carteaud Stat Pearls April 29, 2020; Ann DV 93:493–494, 2013 Darier’s disease Case Rep Dermatol 11:327–333, 2019; J Oral Maxillofac Pathol 21:321, 2017; AD 143:535–540, 2007; Dermatology 188:157–159, 1994 Degos’ disease, benign cutaneous J Dermatol 31:666–670, 2004 Disseminated and recurrent infundibulofolliculitis – neck, trunk, extremities Indian J Dermatol 64:404–406, 2019; J Derm 25:51–53, 1998; Dermatol Clin 6:353–362, 1988; AD 105:580–583, 1972 Elastosis perforans serpiginosa Acta DV 98:822–823, 2018; J Dermatol 24:458–465, 1997

SYNDROMES Acrogeria Dermatol 192:264–268, 1996 Atrichia with keratin cysts – face, neck, scalp; then trunk and extremities Ann DV 121:802–804, 1994 Basaloid follicular hamartoma syndrome (generalized basaloid follicular hamartoma syndrome) – multiple skin-colored, red, and hyperpigmented papules of the face, neck chest, back, proximal extremities, and eyelids; syndrome includes milia-like cysts, comedones, sparse scalp hair, palmar pits, and parallel bands of papules of the neck (zebra stripes) JAAD 49:698–705, 2003; BJD 146:1068–1070, 2002; JAAD 43:189–206, 2000 Bazex-Christol-Dupre syndrome – neck papules, trichoepitheliomas Eur J Med Genet 52:250–255, 2009 Behcet’s syndrome – acneiform lesions; erythema nodosum; nodule AD 138:467–471, 2002 Birt-Hogg –Dube syndrome – autosomal dominant; fibrofolliculomas, trichodiscomas, acrochordon; lung cysts, pneumothorax, renal cancer; mutation in FLCN (folliculin) Am J Clin Dermatol 19:87–101, 2018; AD 133:1163–1166, 1997

Erythromelanosis follicularis faciei Case Rep Dermatol 27:335–339, 2015

Brooke-Spiegler syndrome – multiple familial trichoepitheliomas, bilateral symmetric skin colored papules of face, neck, or chest Dermatol Online J 18:16, 2012

Erythromelanosis follicularis faciei et colli An Bras Dermatol 85:923–925, 2010

Down’s syndrome – deep folliculitis of posterior neck; elastosis perforans serpiginosa

Fibroelastolytic papulosis of the neck – skin colored papules with cobblestoning of face and neck; possibly same as white fibrous papulosis of neck or PXE-like papillary dermal elastolysis AD 148:849–854, 2012; BJD 173:461–466, 1997; post-menopausal and elderly white women Am J Dermatopathol 41:640, 2019; J Cutan Pathol 43:142–147, 2016; JAAD 67:128–135, 2012

Fibroblastic rheumatism – symmetrical polyarthritis, nodules over joints and on palms, elbows, knees, ears, neck, Raynaud’s phenomenon, sclerodactyly; skin lesions resolve spontaneously AD 131:710–712, 1995

Focal dermal elastosis, late onset J Cutan Pathol 39:957–961, 2012 Granuloma annulare Cutis 55:158–160, 1995 Granuloma faciale, extrafacial SkinMed 6:150–151, 2007; BJD 145:360–362, 2001 Granulomatous perioral dermatitis AD 128:1396–1397,1399, 1992 Hailey-Hailey disease JAMA Derm 150:97–99, 2014 Juxtaclavicular beaded lines J Cutan Pathol 18:464–468, 1991 Lichen sclerosus et atrophicus, guttate Indian J Dermatol 60:105, 2015 Lichen spinulosus JAAD 22:261–264, 1990 Lichen striatus An Bras Dermatol 86:142–145, 2011 Lupus miliaris disseminate faciei Ann Saudi Med 34:351–353, 2014 Prurigo pigmentosa Ann DV 146:219–222, 2019 Psoriasis Scruff (terra firme) – teenage neck – personal observation Trichodysplasia spinulosa – follicular crusted papules with keratotic spines; lesions of face, neck with eyebrow alopecia; trichodysplasia spinulosa-associated polyoma virus JAAD 76:suppl 1 AB269, June 1, 2017; AD 147:1215–1220, 2011 Upper dermal elastolysis J Cutan Pathol 21:533–540, 1994 PXE-like papillary dermal elastolysis – side of neck, axilla; postmenopausal and elderly women JAAD 67:128–135, 2012 White fibrous papulosis (fibroelastotic papulosis) – cobblestoning with 2–4 mm skin colored papules, back or sides of neck An Bras Dermatol 95:102–104, 2020; JAAD 67:128–135, 2012; Cut Ocul Toxicol

Hunter’s syndrome – reticulated 2–10 mm skin colored papules over scapulae, chest, neck, arms; X-linked recessive; MPS type II; iduronate-2 sulfatase deficiency; lysosomal accumulation of heparin sulfate and dermatan sulfate; short stature, full lips, coarse facies, macroglossia, clear corneas (unlike Hurler’s syndrome), progressive neurodegeneration, communicating hydrocephalus, valvular and ischemic heart disease, lower respiratory tract infections, adenotonsillar hypertrophy, otitis media, obstructive sleep apnea, diarrhea, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), widely spaced teeth, dolichocephaly, deafness, retinal degeneration, inguinal and umbilical hernias Ped Derm 21:679–681, 2004; AD 113:602–605, 1977 Hypohidrotic ectodermal dysplasia Hautarzt 42:645–647, 1991 Juvenile hyaline fibromatosis (systemic hyalinosis) – translucent papules or nodules of scalp, face, neck, trunk, gingival hypertrophy, flexion contractures of large and small joints Indian J DV Leprol 71:115–118, 2005; J Cutan Pathol 32:438–440, 2005; Ped Derm 21:154–159, 2004; JAAD 16:881–883, 1987 Lipoid proteinosis BJD 151:413–423, 2004; JID 120:345–350, 2003; Hum Molec Genet 11:833–840, 2002 Neurofibromatosis type 1 Nevoid basal cell carcinoma syndrome JAAD 42:939–969, 2000; basal cell carcinomas – skin tag-like lesions in children with nevoid basal cell carcinoma syndrome Clin in Dermatol 23:68–77, 2005; JAAD 44:789–794, 2001 Nevus comedonicus syndrome Yonajo Acta Med 56:59–61, 2013 Phakomatosis pigmentokeratotica – 3 mm pigmented papules of neck (melanocytic nevi); Blaschko epidermal nevus; HRAS mosaic mutation; tendency for squamous cell carcinoma NEJM 381:1458, 2019

686 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Pseudoxanthoma elasticum – linear and reticulated cobblestoned yellow papules and plaques JAAD 42:324–328, 2000; Dermatology 199:3–7, 1999; AD 124:1559, 1988; PXE and acrosclerosis Proc Roy Soc Med 70:567–570, 1977; agminated papules Cutis 102:E5– 7, 2018; perforating PXE Indian J DV Leprol 82:464–466, 2016

syndrome) – necrotic cutaneous abscesses, psoriasiform dermatitis, gingivitis, periodontitis, septicemia, ulcerative stomatitis, pharyngitis, otitis, pneumonia, peritonitis BJD 123:395–401, 1990

PXE-like papillary dermal elastolysis An Bras Dermatol 95:247–249, 2020; Int J Dermatol 58:93–97, 2019; J Cutan Pathol 21:252–255, 1994

Dermatomyositis – epidermal necrosis associated with internal malignancy Cutis 61:190–194, 1998

Reed syndrome – leiomyomatosis The Dermatologist July, 2016, pp47–49 Steatocystoma multiplex – autosomal dominant BMJ Case Rep Sept 26, 2011:bcr0420114165.doi https://doi.org/10.1136/ bcr.4.2011.4165; J Cut Aesthet Surg 2:107–109, 2009 Sweet’s syndrome – red papules and plaques of neck; JAAD 69:557–564, 2013; Eur J Gastro Hepatol 9:715–720, 1997 Tuberous sclerosis – angiofibromas; fibrous cephalic plaques JAAD 78:717–724, 2018; Mymensingh Med J 13:82–85, 2004

TRAUMA Fiddler’s neck BJD 98:669–674, 1978 Pseudofolliculitis barbae BJD 172:878–884, 2015; Dermatol Clin 6:387–395, 1988 Pseudofolliculitis barbae – razor bumps

VASCULAR LESIONS Glomus tumor Pseudo-Kaposi’s sarcoma overlying arteriovenous anastomosis following carotid endarterectomy Tufted angioma – deep red papule, plaque, or nodule of back or neck JAAD 52:616–622, 2005 Venous lakes

NECROSIS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Allergic contact dermatitis – poison ivy or oak NEJM 352:700–707, 2005 Anti-centromere antibodies – ulcers and gangrene of the extremities Br J Rheumatol 36:889–893, 1997 Antiphospholipid syndrome – ear necrosis JAMA 316:450–451, 2016; acral necrosis of toes Cutis 100:206,209–210, 2017; catastrophic anti-phospholipid antibody syndrome Int J Dermatol 58:e130–132, 2019 Arthus reaction – necrosis of skin over deltoid muscle due to hepatitis B virus vaccine Clin Inf Dis 33:906–908, 2001; erythema, edema, hemorrhage, occasional necrosis Bowel arthritis dermatitis syndrome – necrotic papules AD 135:1409–1414, 1999; Cutis 63:17–20, 1999; JAAD 14:792–796, 1986; Mayo Clin Proc 59:43–46, 1984; AD 115:837–839, 1979 Chronic granulomatous disease – necrotic ulcers; bacterial abscesses, perianal abscesses JAAD 36:899–907, 1997; AD 130:105–110, 1994; NEJM 317:687–694, 1987; AD 103:351–357, 1971 Congenital deficiency of leucocyte-adherence glycoproteins (CD11a (LFA-1), CD11b, CD11c, CD18) (leukocyte adhesion deficiency

Connective tissue disease – eosinophilic vasculitis in connective tissue diseases; digital microinfarcts JAAD 35:173–182, 1996

Graft vs. host disease, acute – epidermal necrosis AD 134:602– 612, 1998 Heparin necrosis Thromb Haemost 91:196–197, 2004; Br J Haematol 111:992, 2000; Ann R Coll Surg Engl 81:266–269, 1999; JAAD 37:854–858, 1997; NEJM 336:588–589, 1997; Nephron 68:133–137, 1994; low molecular weight heparin Ann Haematol 77:127–130, 1998; at injection site Dermatology 196:264–265, 1998; Thromb Haemost 78:785–790, 1997; Australas J Dermatol 36:201–203, 1995; eschar and ulceration JAAD 47:766–769, 2002; heparin induced thrombocytopenia (HITT) – blisters with surrounding erythema followed by necrosis; acute arterial or venous occlusion; skin necrosis; livedo racemosa; thrombocytopenia; heparin-PF4 antibodies Curr Opinion Hematol 23:462–470, 2016; JAAD 61:325–332, 2009 Hypersensitivity angiitis AD 138:1296–1298, 2002 Intrauterine blood transfusion – Rh incompatibility Linear IgA disease (TEN) JAAD 31:797–799, 1994 Lupus erythematosus – systemic – necrosis of the proximal nail fold; epidermal necrosis mimicking toxic epidermal necrosis Clin Rheum Dis 8:207, 1982; vasculitis; gangrene of extremity due to vasculitis or thrombosis (anti-phospholipid antibodies) J Rheumatol 13:740–747, 1986; infarcts of fingertips JAAD 48:311–340, 2003; digital gangrene Cureus 12:e6667, 2020; toxic epidermal necrolysis JAAD 48:525–529, 2003 Mixed connective tissue disease; J Cut Med Surg 21:425–451, 2017; Am J Med 52:148–159, 1972 Myeloperoxidase deficiency – lip infection and necrosis Ped Derm 20:519–523, 2003 Pemphigus vegetans NEJM 352:700–707, 2005 PLAID (PLCG2-associated antibody deficiency and immune dysregulation) – autosomal dominant; evaporative cold urticaria; neonatal ulcers in cold sensitive areas; granulomatous lesions sparing flexures; blotchy pruritic red rash, spontaneous ulceration of nasal tip with eschar of nose; erosion of nasal cartilage, neonatal small papules and erosions of fingers and toes; brown granulomatous plaques with telangiectasia and skin atrophy of cheeks, forehead, ears, chin; crusted, ulcerated eroded plaque of nasal tip, ears, tips of fingers and toes (acral necrosis); atopy; recurrent sinopulmonary infections; autoimmune diseases Ped Derm 37:147–149, 2020; JAMADerm 151:627–634, 2015 Rheumatoid vasculitis – purpuric infarcts of paronychial areas (Bywater’s lesions) JAAD 53:191–209, 2005; BJD 77:207–210, 1965; bullae of fingertips and toe-tips with purpura; BJD 77:207–210, 1965; large hemorrhagic lesions, gangrene with necrotizing arteritis; peripheral gangrene JAAD 53:191–209, 2005; mononeuritis multiplex; papulonecrotic lesions JAAD 48:311–340, 2003 SAVI – STING-associated vasculopathy with onset in infancy syndrome (type 1 interferonopathy) – autosomal dominant; gain of function mutation in transmembrane protein 173 (STING) leading to chronic activation of Type I interferon pathway; red plaques of face and hands; chilblain-like lesions; atrophic plaques of hands, telangiectasias of cheeks, nose, chin, lips, acral violaceous scaling plaques and acral cyanosis (livedo reticularis of feet, cheeks, ears, and knees), of fingers, toes, nose, ears, cheeks distal ulcerative lesions with infarcts (erythema then necrosis of cheeks and ears),

Necrosis gangrene of fingers or toes with ainhum, nasal septal perforation, nail dystrophy and nail loss, small for gestational age; paratracheal adenopathy, abnormal pulmonary function tests; severe interstitial lung disease with fibrosis with ground glass and reticulate opacities; gain of function mutation in TMEM173 (stimulator of interferon genes); mimics granulomatosis with polyangiitis Ped Derm 33:602– 614, 2016; JAMADerm 151:872–877, 2015; NEJM 371:507–518, 2014

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Gangrene of abdominal wall – due to intrauterine red-cell transfusion Am J Dis Child 117:593–596, 1969

failure and dialysis, acute leukemia, systemic lupus erythematosus, anti-phospholipid antibody syndrome, Epstein-Barr virus infection, acute respiratory distress syndrome, acute intravascular coagulation, plasmapheresis JAAD 61:325–332, 2009; BJD 151:502–504, 2004; JAAD 47:766–769, 2002; Br J Surg 87:266–272, 2000; Thromb Haemost 78:785–790, 1997; Hematol Oncol Clin North Am 7:1291–1300, 1993; AD 128:105, 108, 1992; AD 123:1701a-1706a, 1987; with mutation of prothrombin gene NEJM 340:735, 1999; with familial type II protein C deficiency Am J Hematol 29:226–229, 1988; with acquired protein C deficiency Intensive Care Med 27:1555, 2001; with protein S deficiency Haemostasis 28:25–30, 1998; with Factor V Leiden and protein S deficiency Clin Lab Haematol 23:261–264, 2001; intravascular coagulation necrosis JAAD 25:882–888, 1991; late onset coumarin warfarin necrosis Am J Hematol 57:233–237, 1998; other associations include bleeding, priapism, hepatitis, alopecia, morbilliform eruptions JAAD 61:325– 332, 2009; massive necrosis mimicking calciphylaxis J Drugs in Dermatol 9:859–863, 2010

Intrauterine epidermal necrosis JAAD 38:712–715, 1998

Cyclophosphamide BJD 143:1356–1358, 2000

Subcutaneous fat necrosis of the newborn – necrotic bulla Ped Derm 20:257–261, 2003

Dactinomycin – flexural cutaneous necrosis with post-inflammatory hyperpigmentation AD 142:1660–1661, 2006

Umbilical artery catheterization – legs, lumbar, buttocks (perinatal gangrene of the buttock); gangrene of legs AD 113:61–63, 1977; unilateral necrosis of buttock Arch Dis Child 55:815–817, 1980; JAAD 3:596–598, 1980

Daunorubicin extravasation Oncol Nurs Forum 25:67–70, 1998

DRUG-INDUCED

DPT vaccination site – embolia cutis medicamentosa (Nicolau syndrome) Actas Dermosifiliogr 95:133–134, 2004

Severe combined immunodeficiency – necrotic bacterial skin infections resembling ecthyma gangrenosum

CONGENITAL LESIONS Anti-phospholipid antibody syndrome, neonatal – arterial thrombotic gangrene of lower leg Ped Derm 28:343–345, 2011

Acetaminophen rectal suppositories – perianal necrosis (ergotism) BJD 170:212–218, 2014 Actinomycin D extravasation Adriamycin – IV J Surg Res 75:61–65, 1998; Cancer Treat Rep 63:1003–1004, 1979; Cancer 38:1087–1094, 1976

Depo-Provera – intramuscular BJD 143:1356–1358, 2000 Dextran injections – intramuscular AD 124:1722–1723, 1988 Doxorubicin hydrochloride – epidermal necrosis Pharmazie 48:772–775, 1993

Calcium salts – IV Dextrose – IV Dopamine – IV Ergot poisoning

Alendronate – osteonecrosis of mandible; halitosis, hypesthesia of lower lip, submental sinus; necrosis of mandible underlying gingiva NEJM 367:551, 2012

Enoxaparin Ann Int Med 125:521–522, 1996

All-trans retinoic acid induction chemotherapy in acute promyelocytic leukemia – fever, scrotal, vulvar, or perineal necrotic ulcers JAMADerm 153:1181–1182, 2017

Epinephrine-containing cream Br J Clin Pract 38:191, 1984

Epidural blockade – necrosis of lower extremities Can J Anaesth 35:628–630, 1988 Fluorescein extravasation Retina 7:89–93, 1987

Amiodarone

5-fluorouracil – epidermal necrosis of psoriatic plaques following intravenous 5-FU BJD 147:824–825, 2002

Amitriptyline Burns 25:768–770, 1999

Flunitrazepam abuse Acta DV 79:171, 1999

Arsenic – endothelial damage

G-CSF – necrotizing vasculitis Ped Derm 17:205–207, 2000

Beta blockers BJD 143:1356–1358, 2000

Gemcitabine SAGE Open Med Case Rep Oct 30, 2018; K Drugs Dermatol 17:582–585, 2018

Bevacizumab (VEGF inhibitor) and irinotecan – steroid-induced striae undergo necrosis AD 147:1226–1227, 2011 Bleomycin – gangrene Eur J Dermatol 8:221, 1998; AD 107:553– 555, 1973 Buprenorphine – intra-arterial injection AD 138:1296–1298, 2002

Heparin-induced skin necrosis – black necrotic bullae of abdomen JAAD 71:1033–1035, 2014 Hydantoin (Dilantin) extravasation

Calcium gluconate infusion – IV JAAD 6:392–395, 1982

Hypertonic saline extravasation J Derm Surg Oncol 19:641–646, 1993

Capecitabine – personal observation

Infusion leakage in the newborn Br J Plast Surg 54:396–399, 2001

Chemotherapy injection site BJD 143:1356–1358, 2000

Interferon alpha injection site JAAD 37:118–120, 1997; pegylated interferon alpha JAAD 53:62–66, 2005

Cisplatin Cancer Treat Rep 67:199, 1983 IV cocaine JAAD 16:462–468, 1987 Crack cocaine – necrosis of ears and legs JAAD 64:1004–1006, 2011; necrotizing vasculitis JAAD 59:483–487, 2008; Neurol Clin 15:945–957, 1997

Interferon beta J Cosmetic Dermatol Aug 22, 2019; JAAD 37:553– 558, 1997; Dermatology 195:52–53, 1997 Interleukin-2 JAAD 29:66–70, 1993 Interleukin-3 BJD 143:1356–1358, 2000

Compazine – intramuscular with infarction

Intra-articular anesthesia BJD 143:1356–1358, 2000

Coumarin necrosis – eschar and ulceration; associations include acquired protein C deficiency in chronic liver disease, chronic renal

Levophed ischemic necrosis – personal observation Mannitol – IV

688

THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Methadone BJD 143:1356–1358, 2000 Methotrexate necrosis – necrosis of psoriatic plaques JAAD 77:247–255, 2017; JAAD 73:484–490, 2015; Cutis 92:148–150, 2013; Cutis 81:413–416, 2008; BMJ 299:980–981, 1989; S Afr Med J 72:888, 1987 Mitomycin C – spillage; penile necrosis JAAD 55:328–331, 2006 Nafcillin – IV Nivolumab – ulcer of scalp; scalp necrosis; giant cell arteritis due to nivolumab JAMADerm 155:1086–1087, 2019 Norepinephrine – IV BJD 143:1356–1358, 2000 Oxymetazoline – intra-arterial injection AD 138:1296–1298, 2002 Paracetamol – fixed drug eruption with eyelid skin necrosis Indian J Ophthalmol 66:1627–1629, 2018 Parenteral nutrition formulation extravasation J Miss State Med Assoc 40:307–311, 1999 Phenergan injection Phenylephrine-induced microvascular occlusion syndrome – livedo racemosa, acral cyanosis and necrosis with hemorrhagic bullae AD 143:1314–1317, 2007 Phenytoin – IV JAAD 28:360–363, 1993; hydantoin (Dilantin) extravasation Photodynamic therapy Photochem Photobiol 68:575–583, 1998 Potassium salts – IV Propylthiouracil vasculitis – blue necrotic ear lesions; fever, arthralgias, and myalgias JAMADerm 151:551–552, 2015 Quinine sulfate – acral necrosis Hautarzt 51:332–335, 2000 Radiation recall – capecitabine, doxorubicin, taxanes, gemcitabine; erythema and desquamation; edema; vesicles and papules; ulceration and skin necrosis The Oncologist 15:1227–1237, 2010 Radioopaque dye – IV Sertraline – giant bulla with necrosis BJD 150:164–166, 2004 Sodium bicarbonate – IV Sodium tetradecyl sulfate extravasation J Derm Surg Oncol 19:641–646, 1993 Streptokinase – IV BMJ 309:378, 1994 Toxic epidermal necrolysis SKINmed 10:373–383, 2012; JAAD 40:458–461, 1999; JAAD 23:870–875, 1990

Alcohol – percutaneous absorption and necrosis in a preterm infant Arch Dis Child 57:477–479, 1982 Anabolic steroids – acne fulminans with necrotic ulcers AD 148:1210–1212, 2012 Antiseptics (isopropyl alcohol) – in newborn Pediatrics 68:587–588, 1981 Buprenorphine, surreptitious intra-arterial administration – livedo racemosa (necrotic livedo reticularis) AD 146:208–209, 2010; high dose buprenorphine injections – livedo with necrosis BJD 172:1412–1414, 2015 Calcium – percutaneous calcium salts (calcium chloride-containing EEG paste on abraded scalp skin) Ped Derm 15:27–30, 1998; Dermatologica 181:324–326, 1990 Collagen implant (bovine) – Zyderm or Zyplast JAAD 25:319–326, 1991; sterile abscesses with local necrosis JAAD 25:319–326, 1991 Crack hands – free base cocaine crack pipe; black burns of fingertips Curr Drug Abuse Rev 5:64–83, 2012; Chest 121:289–291, 2002; Cutis 50:193–194, 1992 Dequalinium (quaternary ammonium antibacterial agent) – necrotizing ulcers of the penis Trans St John’s Hosp Dermatol Soc 51:46–48, 1965 Drug abuse NEJM 277:473–475, 1967 Emmonsia pasteurina – verrucous and black necrotic nodule JAMADerm 151:1263–1264, 2015 Injectable filler necrosis of the face (glabella) JAAD 73:15–24, 2015; nasal ala J Oral Maxillofac Surg 78:133–140, 2020; JAMA Facial Plast Surg 20:207–214, 2018; Plast Reconstr Surg 12:127e-12e, 2008 Orthopedic braces Am J Orthop 27:371–372, 1998 Hepatitis B virus vaccine – Arthus reaction Clin Inf Dis 33:906–908, 2001 Hydrofluoric acid Ann DV 122:512–513, 1995 Intra-arterial injections Irritant contact dermatitis Krokodil (desomorphine) – intravenous drug abuse contaminated with paint thinner, lighter fluid, gasoline, lead, zinc, hydrochloric acid green scaly skin; gangrene down to bone leading to amputation Clin Inf Dis 61:1840–1849, 2015

Vasopressin BJD 143:1356–1358, 2000; Dermatology 195:271– 273, 1997; Cutis 57:330–332, 1996; JAAD 15:393–398, 1986; scrotal and abdominal skin necrosis Dig Dis Sci 30:46–464, 1985

Levamisole-adulterated cocaine – cutaneous necrosis (livedo racemosa) associated with cocaine abuse (cocaine cut with levamisole); retiform purpura with neutropenia and vasculitis; necrosis and purpura of face, ears, nose, and cheeks, trunk; thrombotic vasculopathy; perinuclear ANCA positivity Cutis 102:169–170,175–176, 2018; Clin Inf Dis 61:1840–1849, 2015; J Drugs in Dermatol 10:1204–1207, 2011; Cutis 91:21–24, 2013; JAAD 69:135–142, 2013; Cutis 91:21–24, 2013; JAAD 65:722–725, 2011; AD 146:1320–1321, 2010; Ann Int Med 152:758–759, 2010; paronychial necrosis BJD 140:948–951, 1999; ear necrosis Pediatr Nephrol 14:1057–1058, 2000

Vasopressive agents – peripheral ischemia NEJM 369:1047–1054, 2013

Marijuana – cannabis arteritis – peripheral necrosis over legs JAAD 69:135–142, 2013; toe tip ulcers JAAD 58:S65–67, 2008

Vinorelbine extravasation Tumori 86:289–292, 2000

Naphtha (charcoal lighter fluid), subcutaneous injection Am J Emerg Med 16:508–511, 1998

Tumor necrosis factor J Inflamm 47:180–189, 1995 Ustekinumab – leukocytoclastic vasculitis – purpuric necrotic targetoid bullae J Drugs Dermatol 15:358–361, 2016 Vaccination – DPT – livedoid skin necrosis (Nicolau syndrome) BJD 137:1030–1031, 1997 Vasoconstricting agents

Voriconazole – in graft vs. host disease – giant bullae of hands, feet, and legs which progress to necrosis JAAD 58:484–487, 2008 Warfarin-associated nonuremic calciphylaxis JAMADerm 153–309– 314, 2017

EXOGENOUS AGENTS Acids and alkali

Parenteral nutrition – extravasation of parenteral nutrition in pre-term or low birth weight infants; edema and compartment syndromes; necrosis, acral necrosis, anonychia Ped Derm 32:830–835, 2015 Phosphoric acid Potassium hydroxide, topically, as therapy for molluscum contagiosum Ped Derm 37:224–225, 2020

Necrosis PPD NEJM 295:1263, 1976 Sclerotherapy – high-concentration sclerotherapy for varicose veins Dermatol Surg 26:535–542, 2000 Silicone, injected AD 141:13–15, 2005; Derm Surg 27:198–200, 2001 Tibial cement extrusion J Arthroplasty 13:826–829, 1998 Tongue ring – mucosal necrosis

INFECTIONS AND INFESTATIONS

38:488–490, 1998; eschar and ulceration JAAD 53:213–219, 2005; JAAD 47:766–769, 2002; Aspergillus fumigatus – necrotic purpura with ulcers; verrucous crusted black giant plaque of back Ped Derm 27:403–404, 2010; Aspergillus fumigatus – painful, purpuric necrotic papules and pustules in tattoo BJD 170:1373–1375, 2014 Bacteroides – non-clostridial gas gangrene in diabetics JAMA 233:958–963, 1975 Balamuthia mandrillaris – red plaque with central necrosis; transmitted by organ transplant Clin Inf Dis 63:878–888, 2016 BCG lymphadenopathy with eschar Ped Derm 21:646–651, 2004

Acanthamoeba J Clin Inf Dis 20:1207–1216, 1995; perianal gangrene Trop Doct 12:162–163, 1982; Proc R Soc Med 66:677– 678, 1973; tender red nodules of trunk and extremities with necrosis and eschars AD 147:857–862, 2011

Beetle bite J Cutan Med Surg 4:219–222, 2000

Acinetobacter baumannii – cellulitis with overlying vesicles progress to necrotizing fasciitis with bullae JAAD 75:1–16, 2016; Surg Infect (Larchmt)11:49–57, 2010

Boutonneuse fever

Acremonium – target-like lesions with central necrosis Actinomycosis – necrotic oral plaques Ped Derm 29:519–520, 2012 Aeromonas hydrophilia sepsis – gangrene JAAD 61:733–750, 2009 African tick bite fever (Rickettsia africae) – crusted eschar AD 142:1312–1314, 2006; BJD 143:1109–1110, 2000; hemorrhagic pustule, purpuric papules; transmitted by Amblyomma ticks – high fever, regional adenopathy, arthralgia, myalgia, fatigue, rash in 2–3 days, with eschar, maculopapules, vesicles, and pustules JAAD 48:S18–19, 2003 Alternariosis – necrosis of large section of arm Ped Derm 24:257– 262, 2007 Amebiasis (Entamoeba histolytica) – nasal destruction with malodorous ulcer with gray-white necrotic base; penile ulcers, genital and perianal ulcers Cutis 90: 2012 Angioinvasive fungal infections JAAD 80:869–880, 2019; JAAD 80:883, 898, 2019

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Bejel Bilophila wadsworthia and Escherichia coli – necrotizing fasciitis Brown recluse spider bite – necrotic arachnidism – (L. reclusa) Lancet 378:2039–2047, 2011; J Toxicol Clin Toxicol 21:451–472, 1983–1984; ecchymosis, cyanotic pale hemorrhagic bulla progresses to eschar; sunken bluish patch; Loxosceles rufescens; eschar, necrosis, targetoid: 6 eyes JAMADerm 156:203, 2020; JAMADerm 150:1205–1208, 2014; JAAD 67:347–354, 2012; NEJM 352:700–707, 2005; dermonecrotic lesion with periorbital edema Turk J Pediatr 53:87–90, 2011 Brucellosis – necrotizing vasculitis Burkholderia pseudomallei (melioidosis) – disseminated; ecthymalike lesions Clin Inf Dis 40:988–989, 1053–1054, 2005 especially found in Thailand; ecthyma gangrenosum-like lesions AD 135:311–322, 1999; ecthymatous eschar Clin Inf Dis 40:988– 989,1053–1054, 2005 Buruli ulcer – diffuse erythema, edema, and necrosis of dorsal hand JAMADerm 130:669–671, 2014 Calymmatobacterium granulomatis (Donovanosis) – penile necrosis J Clin Inf Dis 25:24–32, 1997

Anthrax – eschar of the fingers, face, or neck NEJM 372:954– 962, 2015; Cutis 69:23–24, 2002; Cutis 67:488–492, 2001; Clin Inf Dis 19:1009–1014, 1994; Cutis 48:113–114, 1991; Cutis 40:117–118, 1987; eschar and ulceration NEJM 352:700–707, 2005; JAAD 47:766–769, 2002; necrotic papulopustule Ped Derm 24:330–331, 2007; papule develops central vesicle with surrounding brawny edema becomes hemorrhagic, necrotic with satellite vesicles; black eschar, painless ulcer JAAD 65; 1213– 1218, 2011; intravenous drug abuse – edema, necrosis, bullae, compartment syndrome, necrotizing fasciitis Clin Inf Dis 61:1840–1849, 2015

Cancrum oris (noma) – labial and buccal necrosis J Dent Child 48:138–141, 1981

Arthropod bite NEJM 352:700–707, 2005; hypersensitivity to mosquito bites with intense erythema, edema and necrosis AD 139:1601–1607

Carbuncle

Aspergillosis – necrotic papulonodules JAAD 80:869–880, 2019; AD 125:952–956, 1989; large (2–3 cm) eschar with thin erythematous halo SKINmed 13:329–330, 2015; BJD 157:407–409, 2007; NEJM 352:700–707, 2005; AD 141:633–638, 2005; Clin Inf Dis 22:1102– 1104, 1996; Ped Inf Dis 12:673–682, 1993; A. flavus, primary cutaneous – necrotic ulcer AD 141:1035–1040, 2005; violaceous and necrotic plaque – primary cutaneous aspergillosis at site of cyanoacrylate skin adhesive Ped Derm 35:494–497, 2018; primary cutaneous aspergillosis in premature infant – necrotic eschar blanketing entire back Ped Derm 36:709–710, 2019; necrotizing dermal plaque BJD 85(suppl 17):95–97, 1971; primary cutaneous aspergillosis JAAD 38:797–798, 1998; Infect Control Hosp Epidemiol 17:365–366, 1996; primary cutaneous aspergillosis in premature infants Ped Derm 19:439–444, 2002; A. flavus JAAD 46:945–947, 2002; zosteriform A. flavus – black eschar JAAD

Cellulitis, erysipelas

Candida tropicalis – targetoid lesions with central necrosis JAAD 80:869–880, 2019; J Hosp Infect 50:316–319, 2002; Rev Iberoam Micol 16:235–237, 1999; Mycoses 40:17–20, 1997; AD 115:234– 235, 1979 Candidiasis, disseminated – necrotic eschar and pustules; ecthyma gangrenosum-like lesion Capnocytophaga canimorsus sepsis – dog and cat bites; necrosis with eschar Cutis 60:95–97, 1997; JAAD 33:1019–1029, 1995 Caterpillars, poisonous Toxicon 153:39–52, 2018; Ann DV 125:489– 491, 1998 Cheyletiella mites – dogs, cats; papulovesicles, pustules, necrosis JAAD 50:819–842, 2004; AD 116:435–437, 1980 Chikungunya fever (Chikungunya virus) – Africa, Middle East, Europe, India, Southeast Asia; fever, arthralgias, morbilliform eruption; polyarthritis and tenosynovitis; hepatitis, myocarditis, hemorrhage, meningitis, encephalitis; palpebral edema; purpuric butterfly eruption of face; necrosis of skin of nose Clin Inf Dis 62:78–81, 2016 Chromobacterium violaceum NEJM 352:700–707, 2005; distal gangrene JAAD 54:S224–228, 2006 Clostridium botulinum – wound botulism in drug addicts Clin Inf Dis 31:1018–1024, 2000 Clostridial cellulitis of the newborn AD 113:683–684, 1977

690 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Clostridium perfringens (gas gangrene) – most common cause of necrotizing anorectal and perianal infection Surgery 86:655–662, 1979 Clostridium septicum – gas gangrene and myonecrosis Clostridium welchii

Erysipelothrix rhusiopathiae – rare systemic form with localized swellings with central necrosis Escherichia coli – non-clostridial gas gangrene in diabetics JAMA 233:958–963, 1975

Coccidioidomycosis – primary cutaneous coccidioidomycosis; necrotic papule JAAD 49:944–949, 2003

Fire coral (Millepora spp) – scuba divers; dermatitis, bullae, hemorrhagic bullae, necrosis, ulceration, urticaria; late lichenoid and granulomatous reactions JAAD 61:733–750, 2009

Colletotrichum gloeosporioides (plant pathogen) – necrotic ulcers JAMADerm 1511383–1384, 2015

Flavobacterium odoratum – necrotizing fasciitis J Clin Inf Dis 21:1337–1338, 1995

Corynebacterium urealyticum Clin Inf Dis 22:853–855, 1996

Fournier’s gangrene NEJM 376:1158: AD 142:797–798, 2006; Clin Inf Dis 40:990–996, 2005

Covid-19 – coronavirus; hypercoagulability with acral necrosis – personal observation

Diphtheria, cutaneous (Corynebacterium diphtheria) – black n

Fusarium – sepsis; red-gray macules or papules with central eschar JAAD 47:659–666, 2002; Ped Derm 9:62–65, 1992; Fusarium solani – target-like lesions with central necrosis; violaceous nodules with central necrosis AD 146:1037–1042, 2010; Clin Inf Dis 32:1237– 1240, 2001; Eur J Clin Microbiol Infect Dis 13:152–161, 1994; purpuric eschar AD 147:1317–1322, 2011; cellulitis with necrosis Am J Clin Pathol 75:304–311,1981; necrotic nodule of temple AD 146:439–444, 2010; J Pediatr 84:561–564, 1974; F. falciforme – starts as red nodule then evolves into red plaques, vesicles, pustules, with or without central necrosis BJD 157:407–409, 2007

necrotic ulcers of penis and scrotum Cutis 79:371–377, 2007

Fusobacterium – abscesses with necrosis

Cytomegalovirus infection – necrotic ulcers of the scalp Ped Derm 31:729–731, 2014

Gangrenous and crepitant cellulitis   Clostridium perfringens   Infected vascular gangrene   Nonclostridial crepitant cellulitis (anaerobes)   Phycomycotic gangrenous cellulitis   Progressive bacterial synergistic gangrene   Vibrio vulnificus

Cowpox (feline orthopoxvirus) – eschar; necrotic papule; tongue ulcer, targetoid and umbilicated indurated papules, vesicles, pustules with central necrosis; exposure to pet rat Clin Inf Dis 68:1063–1064, 2019; BJD 173:535–539, 2015; JAAD 49:513–518, 2003; BJD 145:146–150, 2001 Cryptococcosis NEJM 352:700–707, 2005; umbilicated papules with central necrosis AD 142:921–926, 2006

Ecthyma – eschar and ulceration JAAD 47:766–769, 2002 Ecthyma gangrenosum – Pseudomonas aeruginosa NEJM 352:700– 707, 2005; JAAD 11:781–787, 1984; Pseudomonas cepacia AD 113:199–202, 1977; gram-negative bacteria Postgrad Med 106:249– 250, 1999; AD 121:873–876, 1985; JAAD 11:781–787, 1984; Escherichia coli J Clin Gastroenterol 4:145–148, 1982; Rev Inf Dis 2:854–865, 1980; Aeromonas hydrophila NY State J Med 82:1461– 1464, 1982; J Pediatr 83:100–101, 1973; Klebsiella pneumoniae Int J Dermatol 34:216–217, 1995; South Med J 84:790–793, 1991; Xanthomonas maltophilia Ann Int Med 121:969–973, 1994; Morganella morganii Mil Med 153:400–401, 1988; Serratia marcescens Rev Inf Dis 2:854–865, 1980; Citrobacter freundii JAAD 50:S114–117, 2004; Corynebacterium diphtheria JAAD 50:s114–117, 2004; Neisseria gonorrhoeae; Yersinia pestis; Citrobacter freundii; Staphylococcus aureus; Streptococcus pyogenes; Aspergillus fumigatus; Aspergillus niger Am J Clin Pathol 72:230–232, 1979; Candida albicans Am J Med 70:1133–1135, 1982; Exserohilum species Ped Derm 20:495–497, 2003; Vibrio, Rhizopus, Fusarium solani; Scytalidium dimidiatum J Clin Microbiol Infect Dis 12:118–121, 1993; Pseudallescheria boydii, Curvularia sp. Bone Marrow Transplant 27:1311–1313, 2001; herpes simplex Clin Infect Dis 29:454–455, 1999 Endocarditis, bacterial – necrosis in children AD 133:1500–1501, 1997; subacute bacterial endocarditis with vasculitis; subacute bacterial endocarditis – Streptococcus viridans with cutaneous vasculitis; Osler’s nodes (painful hemorrhagic bulla of thumb tip); extensive distal purpura with necrosis of legs; Janeway lesion – purpuric macule of sole; conjunctival hemorrhage JAMADerm 150:494– 500, 2014; extensive cutaneous necrosis Eur Heart J Dec 23, 2019 Acute bacterial endocarditis – personal observation Enteroviral infections – leukocytoclastic vasculitis – personal observation Epidemic typhus (Rickettsia prowazekii) – pink macules on sides of trunk, spreads centrifugally; flushed face with injected conjunctivae; then rash becomes deeper red, then purpuric; gangrene of finger, toes, genitalia, nose JAAD 2:359–373, 1980 Chronic active Epstein-Barr virus – vulvitis, hemorrhagic cheilitis, necrotic ulcers, periorbital erythema and edema, maxillary sinusitis, hepatosplenomegaly BJD 173:1266–1270, 2015

Gemella morbillorum – necrotizing fasciitis JAAD 52:704–705, 2005 Glanders – eschar and ulceration JAAD 47:766–769, 2002 Gonococcemia NEJM 352:700–707, 2005; periarticular lesions appear in crops with red macules, papules, vesicles with red halo, pustules, bullae becoming hemorrhagic and necrotic; suppurative arthritis and tenosynovitis Ann Int Med 102:229–243, 1985; NEJM 282:793–794, 1970; in children AD 133:1500–1501, 1997 Gypsy moth caterpillar reaction JAAD 62:1–10,13–28, 2010 Hepatitis C – with cryoglobulins; thrombotic vasculitis AD 131:1185– 1193, 1995 Herpes simplex virus – necrotizing balanitis JAMA 248:215–216, 1982; Br J Vener Dis 55:48–51, 1979; necrotic digits in chronic herpes simplex JAAD 60:484–486, 2009; neonatal herpes simplex – necrotic plaque of scalp at site of fetal monitor electrode placement Herpes zoster – cutaneous necrosis in AIDS Clin Dermatol 38:160–175, 2020; jaw necrosis Oral Surg 56:39–46, 1983; purpuric, umbilicated, necrotic bullae of leg AD 147:235–240, 2011; red plaque of face with necrosis Cutis 96:364–390, 2015 HHV6 and protein S deficiency (anti-protein S antibodies) – disseminated intravascular coagulation BJD 161:181–183, 2009 Histoplasmosis – necrotic papules and ulcers BJD 113:345–348, 1985 HIV disease – polyarteritis-like vasculitis with acral necrosis J Clin Inf Dis 23:659–661, 1996 Hyalohyphomycosis – necrotic papulonodules JAAD 80:869–880, 2019; Clin Inf Dis 35:909–920, 2002; Rev Inst Trop Sao Paulo 39:227–230, 1997 Insect bite – especially in Hodgkin’s disease; eschar and ulceration JAAD 47:766–769, 2002; necrosis due to hypersensitivity to mosquito bites in patients with Epstein-Barr virus infection JAAD 72:1–19, 2015; mosquito bite hypersensitivity syndrome in EBV-associated natural killer cell leukemia/lymphoma – clear or

Necrosis hemorrhagic bullae with necrosis, ulceration and scar formation JAAD 45:569–578, 2001 Klebsiella sepsis – including non-clostridial gas gangrene in diabetics JAMA 233:958–963, 1975 Leclaria adecarboxylata – cellulitis with necrotic pustules in acute lymphoblastic leukemia Ped Derm 28:162–164, 2011 Leishmaniasis – eschar and ulceration NEJM 352:700–707, 2005; JAAD 47:766–769, 2002; large necrotic ulcer of dorsum of hand in AIDS BJD 160:311–318, 2009; necrosis of lips Mycoses 41 Suppl2:78–80, 1998(German); JAAD 28:495–496, 1993; Dermatologica 150:292–294, 1975; L. aethiopica – lip edema Trans R Soc Trop Med Hyg 63:708–737, 1969; espundia (mucocutaneous leishmaniasis) – nasopharyngeal mutilation with protuberant lips Am J Trop Med Hyg 59:49–52, 1998; erythema nodosum leprosum – targetoid red nodules with central necrosis AD 144:821–822, 2008 Leprosy – plantar necrotic blister; Lucio’s phenomenon – bullae and necrosis leaving deep painful ulcers; necrotic ulcerated plaques of face and extremities JAMADerm 152:333–334, 2016; Int J Lepr 47:161–166, 1979; stellate necrosis due to hemorrhagic infarcts of legs, forearms, buttocks with lymphadenopathy, splenomegaly in Lucio’s phenomenon; fever, anemia, hepatosplenomegaly JAAD 83:17–30, 2020; JAAD 71:795–803, 2014; JAAD 51:416–426, 2004; lepromatous leprosy including erythema nodosum leprosum (vasculitis) JAAD 51:416–426, 2004; AD 111:1575–1580, 1975; eschar and ulceration JAAD 47:766–769, 2002; erythema nodosum leprosum Rheum (Oxford) 58:85, 2019; Lucio’s phenomenon – serpiginous polycyclic necrotic ulcers J Clin Aesthet Dermatol 12:35–38, 2019 Lyme disease – vesicular variant with secondary necrosis NEJM 352:700–707, 2005; JAAD 49:363–392, 2003 Malaria Mediterranean spotted fever AD 139:1545–1552, 2003 Meningococcemia Ann Plast Surg 46:199–200, 2001; purpura fulminans Burns 24:272–274, 1998; chronic meningococcemia – necrotic papule AD 144:770–773, 2008; Ped Derm 13:483–487, 1996 Milker’s nodule – eschar and ulceration JAAD 47:766–769, 2002 Millipede burns – necrosis of toes Cutis 103:195–196, 2019 Moths – Podalia, Megalopyge, or Saturniidae moths; necrosis due to envenomation with larval forms of moths (erucism) JAAD 67:331–344, 2012 Mucormycosis – necrotic papulonodules JAAD 80:869–880, 2019; Rhizopus oryzae (accounts for 70% of all mucormycosis), Absidia corymbifera, Cunninghamella bertholletiae, Rhizomucor pusillus Clin Derm 37:447 = 467, 2019; BJD 150:1212–1213, 2004; Mucor circinelloides, Apophysomyces elegans, Saksenaea vasiformis; face, scalp, extremities – necrotic ulcer Ped Derm 20:411–415, 2003; AD 136:1165–1170, 2000; AD 133:249–251, 1997; J Clin Inf Dis 19:67–76, 1994; necrotizing cutaneous mucormycosis NEJM 367:2214–2225, 2012; ptosis with upper eyelid edema and necrosis JAMA 309:2382–2383, 2013; rhino-orbital-cerebral mucormycosis – black necrotic plaque of medial eyelids Cutis 94:168, 195–196, 2014; palatal ulcer, necrosis JAMADerm 155:109–110, 2019; Clin Inf Dis 40:990–996, 2005; Oral Surg 68:624–627, 1989; unilateral localized facial edema with slight erythema; within days goes on to necrosis JAAD 66:975–984, 2012; eschar and ulceration JAAD 47:766–769, 2002; rhino-orbital mucormycosis – palatal and nasal mucosal necrosis NEJM 341:265–273, 1999; slowly progressive cutaneous rhinofacial and pulmonary mucormycosis due to Mucor irregularis Clin Inf Dis 56:993–995, 2013; Rhizopus AD 125:952–956, 1989; Rhizopus azygosporus BJD 153:428–430, 2005 Mycetoma JAAD 32: 897–900, 1995

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Mycobacterium chelonei var. abscessus Mycobacterium haemophilum – necrotic ulcer J Infection 23:303– 306, 1991 Mycobacterium kansasii – papulonecrotic tuberculid JAAD 40:359–363, 1999; JAAD 36:497–499, 1997 Mycobacterium marinum Mycobacterium tuberculosis NEJM 352:700–707, 2005; primary inoculation; miliary tuberculosis – large crops of blue papules, vesicles, pustules, hemorrhagic papules; red nodules; vesicles become necrotic to form ulcers JAAD 50:S110–113, 2004; Practitioner 222:390–393, 1979; Am J Med 56:459–505, 1974; AD 99:64–69, 1969; lupus vulgaris; starts as red-brown plaque, enlarges with serpiginous margin or as discoid plaques; vegetating forms – ulcerate, areas of necrosis, invasion of mucous membranes with destruction of cartilage (lupus vorax); head, neck, around nose, extremities, trunk Int J Dermatol 26:578–581, 1987; Acta Tuberc Scand 39(Suppl 49):1–137, 1960; lupus vulgaris, miliary, papulonecrotic tuberculid Am J Clin Dermatol 3:319–328, 2002; Dermatologica 173:189–195, 1986; BJD 91:263–270, 1974; congenital tuberculosis – red papule with central necrosis AD 117:460–464, 1981; penile gangrene; eschar and ulceration JAAD 47:766–769, 2002 Mycobacterium ulcerans (Buruli ulcer) – necrotic leg ulcer JAMADerm 151:1137–1139, 2015; NEJM 352:700–707, 2005 Mycoplasma pneumoniae – purpura and necrosis Clin Exp Immunol 14:531–539, 1973 Necrolytic acral erythema – hepatitis C infection Int J Dermatol 35:252–256, 1996 Necrotizing fasciitis – necrotic ulcer Ped Derm 29:264–269, 2012; Streptococcus pyogenes Curr Prob in Dermatol 14:183–220, 2002; Ann DV 128:376–381, 2001; methicillin-resistant Staphylococcus aureus NEJM 352:1445–1453, 2005; Streptococcus pneumoniae – due to intramuscular injection Clin Inf Dis 33:740–744, 2001; Serratia marcescens Clin Inf Dis 23:648–649, 1996; JAAD 20:774–778, 1989; Bacteroides spp. in penile necrotizing fasciitis JAAD 37:1–24, 1997; neonatal Pediatrics 103:53, 1999; in infancy Ped Derm 2:55–63, 1984; Clostridial cellulitis (gangrene); progressive synergistic gangrene; gangrenous cellulitis (Pseudomonas); Fournier’s gangrene; periorbital AD 140:664–666, 2004; Klebsiella pneumonia – massive edema, erythema, necrosis of thigh Clin Inf Dis 56:1457,1505–1506, 2013  Most common organisms of necrotizing soft tissue infections are: Infection 47:677–679, 2019; Clin Infect Dis 41:1373–1406, 2005   Streptococcus pyogenes   Staphylococcus aureus   Vibrio vulnificus   Anaerobic streptococci   Klebsiella pneumoniae New Jersey novel polyoma virus sepsis JAAD 1:538–540, 2015 Niquim toadfish envenomation Am J Trop Med Hyg 101:476–477, 2019 Nocardia asteroides AD 121:898–900, 1985; J Inf Dis 134:286–289, 1976 Noma (cancrum oris) (necrotizing gingivitis) – Fusobacterium necrophorum, Prevotella intermedia, alpha-­hemolytic streptococci, Actinomyces spp. Oral Dis 5:144–149,156–162, 1999; associated with malnutrition, unsafe drinking water, poor sanitation, poor oral health Am J Trop Med Hyg 60:150–156, 1999; Cutis 39:501–502, 1987; J Maxillofac Surg 7:293–298, 1979 Noma neonatorum – Pseudomonas infection Ped Inf Dis 21:83–84, 2002 Non-clostridial gas gangrene – cellulitis with necrosis; Streptococcus anginosus, Strep faecalis, aerobic strep, E. coli, Proteus, Bacteroides, Klebsiella spp. JAAD 40:347–349, 1999; Diabetalogia 13:373–376, 1977

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

North American blastomycosis North Asian tick typhus Orf – eschar and ulceration JAAD 47:766–769, 2002 Orthopoxvirus – facial necrosis; on prednisone for Crohn’s disease Hautarzt 70:715–722, 2019 Osteomyelitis-associated vasculitis – personal observation Paecilomyces lilacinus – red nodules with necrotic centers Ann Int Med 125:799–806, 1996; ecthyma gangrenosum-­like JAAD 39:401–409, 1998 Phaeoacremonium inflatipes – fungemia in child with aplastic anemia; swelling and necrosis of lips, periorbital edema, neck swelling Clin Inf Dis 40:1067–1068, 2005 Phaeohyphomycosis, subcutaneous Ped Inf Dis 5:380–382, 1986; phaeomycotic cyst of the hand – Phialophora, Cladosporium, Alternaria JAAD 8:1–16, 1983 Phagedenic balanitis Phlegmon – necrotic cutaneous phlegmon Plague (Yersinia pestis) – ecthyma gangrenosum-like lesions at site of initial flea bite; eschars AD 135:311–322, 1999; Clin Inf Dis 19:655–663, 1994; eschar and ulceration JAAD 47:766–769, 2002 Portuguese man-of-war stings J Emerg Med 10:71–77, 1992 Pseudallescheria boydii – mycetoma – bulla with central necrosis AD 132:382–384, 1996 Pseudomonas – ecthyma gangrenosum in Pseudomonas sepsis; Pseudomonas aeruginosa – ecthyma gangrenosum with severe facial edema AD 142:1663–1664, 2006; eschar and ulceration JAAD 47:766–769, 2002; JAAD 11:781–787, 1984; Arch Int Med 128:591–595, 1971; noma neonatorum – gangrenous changes in oronasal and perineal areas, scrotum, and eyelids (Pseudomonas in infants) Lancet 2:289–291, 1978; Pseudomonas sepsis – penile gangrene J Urol 124:431–432, 1980; non-clostridial gas gangrene in diabetics JAMA 233:958–963, 1975; abscess – personal observation Pythium insidiosum (pythiosis) (alga) (aquatic oocyte) – necrotizing hemorrhagic plaque; ascending gangrene of legs; Thailand; painful subcutaneous nodules, eyelid swelling and periorbital cellulitis, facial swelling, ulcer of arm or leg, pustules evolving into ulcers BJD 175:394–397, 2016; J Infect Dis 159:274–280, 1989; cellulitis, infarcts, ulcers JAAD 52:1062–1068, 2005   Differential diagnosis includes:   Aeromonas hydrophilia   Aspergillus   Fusarium   Mucor, Rhizopus   Vibrio vulnificus Queensland tick typhus AD 139:1545–1552, 2003 Rat bite fever (Sodoku) – Spirillum minor – eschar (acrally); macular and petechial rash on palms and soles; palmar papules and pustules with necrosis; acral hemorrhagic pustules; acral morbilliform eruption with petechiae, vesicles, and pustules; headache, migratory polyarthralgias AD 148:1411–1416, 2012; Clin Inf Dis 43:1585–1586, 1616–1617, 2006; JAAD 38:330–332, 1998; Ann Emerg Med 14:1116–1118, 1985; eschar and ulceration JAAD 47:766–769, 2002 Rickettsia parkeri rickettsiosis – Southeastern United States; Gulf coast tick (Amblyomma maculatum); eschar with surrounding petechiae, fever, lethargy, fatigue, headache, myalgia, arthralgia, morbilliform or vesiculopapular or papulopustular rash of trunk and extremities, palms and soles, and occasionally the face 0.5 to 4 days after fever; some lesions with small vesicle or pustule; morbilliform eruptions, discrete round macules and papules AD 146:641–648, 2010; Clin Inf Dis 47:1188–1196, 2008

Rickettsialpox (Rickettsia akari) (Kew Gardens spotted fever) house mouse mite bite (Liponyssus (Allodermanyssus) sanguineus) Ped Derm 29:767–768, 2012; NY Med 2:27–28, 1946; eschars in rickettsialpox, R. conorii, R. sibirica, R. australis, R. japonicum AD 139:1545–1552, 2003; Clin Inf Dis 18:624–626, 1994; eschar and ulceration JAAD 47:766–769, 2002 Rocky Mountain spotted fever JAAD 49:363–392, 2003; Clin Inf Dis 16:629–634, 1993; eschar at bite site; DIC J Clin Inf Dis 21:429, 1995; massive skin necrosis South Med J 71:1337–1340, 1978 Scedosporium apiospermum – septic hemorrhagic necrotic bullae Cutis 84:275–278, 2009 Scopulariopsis Scorpion sting – pain, necrosis, hemorrhagic bullae; pulmonary edema, shock, death JAAD 67:347–354, 2012 Scrub typhus (Orientia (Rickettsia) tsutsugamushi) (larval stage of trombiculid mites (chiggers)) – headache and conjunctivitis; eschar with black crust; generalized macular or morbilliform rash Clin Inf Dis 39:1329–1335, 2004; AD 139:1545–1552, 2003; JAAD 2:359–373, 1980; eschar and ulceration JAAD 47:766– 769, 2002 Sea anemone sting Serratia marcescens – including necrotizing fasciitis J Clin Inf Dis 23:648–649, 1996 Siberian tick typhus AD 139:1545–1552, 2003 Smallpox vaccination Clin Inf Dis 37:241–250, 2003; progressive vaccinia Clin Inf Dis 37:251–271, 2003 Snake bites – edema, erythema, pain, and necrosis NEJM 347:347–356, 2002; green pit viper Am J Trop Med 58:22–25, 1998; spitting cobra (Naja nigricollis) Toxicon 25:665–672, 1987; Spider bites Trans R Soc Trop Med Hyg 92:546–548, 1998; South Med J 69:887–891, 1976; brown recluse spider bite JAAD 44:561–573, 2001; eschar and ulceration JAAD 47:766–769, 2002 Sporotrichosis NEJM 352:700–707, 2005; necrotic plaques Cutis 78:253–256, 2006;; eschar of forehead – fixed cutaneous neonatal sporotrichosis Ped Derm 26:563–565, 2009; necrotic facial mass Dermatol Online J July 15, 2017 Staphylococcus aureus NEJM 352:700–707, 2005; Staphylococcus aureus purpura fulminans and toxic shock syndrome Clin Inf Dis 40:941–947, 2005; MRSA abscess – necrotic papule AD 144:952–954, 2008; methicillin-resistant Staphylococcus aureus – ecthyma gangrenosum (hemorrhagic necrotic bulla) Cutis 90:67–69, 2012; ecthyma gangrenosum lesion Ped Derm 29:320–323, 2012 Staphylococcal scalded skin syndrome Stenotrophomonas maltophilia (formerly Pseudomonas maltophilia) (Xanthomonas maltophilia) – cellulitis, nodules, ecthyma gangrenosum lesions Eur J Clin Microbiol Infect Dis 28:719–730, 2009lJ Eur Acad Dermatol Venereol 21:1298–1300, 2007; Ann Pharmacother 36:63–66, 2002; JAAD 37:836–838, 1997; Can J Infect Dis 7:383–385, 1996 Stingray bite Cutis 78:93–94, 2006; BJD 143:1074–1077, 2000 Streptococcus pyogenes – necrotizing fasciitis with toxic shock syndrome Clin Infect Dis 51:58–65, 2010; acute necrotizing infection following bites or scratches of dogs or cats NEJM 352:700–707, 2005; Ann DV 123:804–806, 1996; ecthyma gangrenosum-like lesion (erythematous plaque with central black necrosis) in disseminated streptococcal disease JAMA 311:957–958, 2014 Streptococcus pneumoniae Clin Inf Dis 21:697–698, 1995; penile gangrene Subcutaneous phaeohyphomycosis – Corynespora cassiicola (plant pathogen of leaf spotting disease) in CARD9 deficiency BJD 174:176–179, 2016

Necrosis Synergistic necrotizing gangrene (Meleney’s synergistic gangrene); Surgery 86:655–662, 1979; Arch Surg 9:317–364, 1924 Syphilis – malignant lues – necrotic papules and nodules JAMA Derm 149:1429–1430, 2013; NEJM 352:700–707, 2005; JAAD 22:1061–1067, 1990; penile gangrene Talaromyces marneffei – necrotic papules and/or nodules JAAD 54:730–732, 2006; JAAD 37:450–472, 1997; Clin Inf Dis 23: 125–130, 1996; Lancet 344:110–113, 1994; Mycoses 34: 245–249, 1991 Tanapox – umbilicated papule progressing to necrosis JAAD 44:1–14, 2001 Tick bites – especially soft ticks JAAD 49:363–392, 2003 Tick typhus (Boutonneuse fever, Kenya tick typhus, African and Indian tick typhus) (ixodid ticks) – small ulcer at site of tick bite (tache noire) – black necrotic center with red halo; pink morbilliform eruption of forearms, then generalizes, involving face, palms, and soles; may be hemorrhagic; recovery uneventful JAAD 2:359–373, 1980; eschar and ulceration JAAD 47:766– 769, 2002 Toxoplasmosis, congenital – necrotic papules JAAD 60:897–925, 2009 Trichosporon beigelii AD 129:1020–1023, 1993 Tropical ulcer – eschar and ulceration JAAD 47:766–769, 2002 Trypanosoma brucei rhodesiense – necrotic chancre J Clin Inf Dis 23:847–848, 1996 Tsutsugamushi fever Dtsch Med Wochenschr 123:562–566, 1998 Tularemia – necrotic papule Cutis 54:279–286, 1994; eschar and ulceration NEJM 352:700–707, 2005; JAAD 47:766–769, 2002; skin slough from hamster bite MMWR 53:1202–1203, 2005 Tungiasis – black eschar in paronychial fold Vaccinia – progressive vaccinia J Clin Inf Dis 25:911–914, 1997 Varicella – varicella gangrenosa Arch Dis Child 30:177–179, 1955; chronic varicella zoster virus in AIDS AD 124:1011–1012, 1988; penile gangrene in infancy; atypical recurrent varicella with vesiculopapular lesions with central necrosis JAAD 48:448–452, 2003; varicella with anti-protein S antibodies, protein S deficiency and DIC J Thromb Haemost 3: 1243–1249, 2005 Venoms Vibrio vulnificus sepsis JAAD 46:S144–145, 2002; Ann DV 128:653–655, 2001; JAAD 24:397–403, 1991 Yaws Zygomycosis AD 140:877–882, 2004; JAAD 32:346–351, 1995; Rhizopus arrhizus; bull’s eye infarct JAAD 51:996–1001, 2004; JAMA 2254:737–738, 1973; Apophysomyces elegans, Saksenaea vasiformis J Clin Inf Dis 24:580–583, 1997; J Clin Inf Dis 19:67–76, 1994; Rhizopus – necrotic purpuric plaque of arm Ped Derm 31:249–250, 2014; Rhizopus azygosporus BJ Inf Dis 3:428–430, 2005

INFILTRATIVE LESIONS Langerhans cell histiocytosis NEJM 352:700–707, 2005; selfregressive Langerhans cell histiocytosis (Hashimoto-­Pritzker disease) – hypopigmented macules of trunk, solitary papules with necrosis, erosive and ulcerated papules, keratotic plantar papules AD 146:149–156, 2010 Langerhans cell histiocytosis in the adult – scrotal ulcer; solitary pink papule; red papules of trunk; ulceronecrotic plaque of scalp; perianal plaque; perianal dermatitis BJD 167:1287–1294, 2012

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Reactive intravascular histiocytosis – black necrotic eschar of scrotum and gluteal cleft; associated with tonsillitis; possibly related to reactive angioendotheliomatosis BJD 154:560–563, 2006 Waldenstrom’s macroglobulinemia – necrotic papules and psoriasiform plaques of knees Annual AAD Meeting 2000

INFLAMMATORY DISORDERS Chondrodermatitis nodularis chronica helicis – necrotic ear Cutis 98:293,301–302, 2016 Dermatitis gangrenosum infantum – multiple necrotic ulcers complicating varicella, seborrheic dermatitis BJD 75:206–211, 1963 Erythema multiforme Medicine 68:133–140, 1989; JAAD 8:763– 765, 1983; Stevens-Johnson syndrome Malignant pyoderma – papulopustules, skin ulcers, violaceous nodules with central necrosis, tongue, pharyngeal, and nasal ulcers AD 146:102–103, 2010; AD 98:561–576, 1968 Nodular panniculitis, idiopathic – overlying necrosis with drainage of oily brown serous fluid Medicine 64:181–191, 1985 Pyoderma gangrenosum BJD 157:1235–1239, 2007; NEJM 352:700–707, 2005; Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988 Pyoderma gangrenosum-like lesions, polyarthritis, and lung cysts with ANCA to azurocidin – umbilicated necrotic lesions Clin Exp Immunol 103:397–402, 1996 Sarcoid – resembling papulonecrotic tuberculid AD Syphilol 13:675–676, 1926 Stevens-Johnson syndrome – personal observation

METABOLIC DISEASES Acrodermatitis enteropathica – black necrotic lesions Calcific uremic arteriolopathy NEJM 352:700–707, 2005 Calcific vasculopathy of chronic renal failure – personal observation Calcinosis cutis – metastatic calcification AD 106:398–402, 1972 Calciphylaxis (vascular calcification cutaneous necrosis syndrome) (cutaneous calcinosis in end stage renal disease) – necrotic cutaneous ulcers, livedo racemosa (livedoid necrosis), hemorrhagic patches, indurated plaques, hemorrhagic bullae NEJM 379:397–400, 2018; NEJM 378:1704–1714, 2018; JAAD 77:241–246, 2017; JAMA Derm 149:946–949, 2013; JAMA Derm 149:163–167, 2013;; Am J Dermatopathol 33:796–802, 2011; JAAD 58:458–471, 2008; CIASN 3:1139–1143, 2008; JAAD 56:569–579, 2007; Ped Derm 23:266–272, 2006; JAAD 58:458–471, 2008; AD 143:791–796, 2007; AD 140:1045– 1048, 2004; J Dermatol 28:27–31, 2001; Br J Plast Surg 53:253–255, 2000; J Cutan Med Surg 2:245–248, 1998; JAAD 40:979–987, 1999; JAAD 33:53–58, 1995; JAAD 33:954–962, 1995; JAAD 33:954–962, 1995; AD 127:225–230, 1991; stellate necrosis JAMADerm 130:671– 673, 2014; stellate necrosis with calciphylaxis associated with pancreatic carcinoma BJD 171:1247–1248, 2014; penile necrosis JAAD 54:736–737, 2006; penile necrosis JAAD 82:799–816, 2020; calciphylaxis with stellate necrosis and retiform purpura unassociated with renal disease (non-uremic calciphylaxis) – stellate necrosis beginning as mottled purpuric reticulated patches; associated with hyperparathyroidism, malignancy, alcoholic liver disease, connective tissue disease, diabetes mellitus, chemotherapy-­induced protein C or S deficiency JAMA 310:1281–1282, 2013; associated with hypoalbuminemia, malignancy, systemic corticosteroid therapy, coumarin, chemotherapy, systemic inflammation, cirrhosis, protein C or S deficiency, obesity, rapid weight loss, infection AD 145:451–458, 2009; warfarin associate JAMADerm 153:309–314, 2017

694 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Catastrophic anti-phospholipid antibody syndrome – personal observation

Prothrombin G20210A – mutation (heterozygous) Pediatr Hematol Oncol 16:561–564, 1999

Cold agglutinins BJD 139:1068–1072, 1998; JAAD 19:356–357, 1988; at site of transfusion JAAD 19:356–357, 1988; intravascular coagulation necrosis JAAD 25:882–888, 1991; digital necrosis Ann DV 145:761–764, 2018

Purpura fulminans, neonatal – purpura or cellulitis-like areas evolving into necrotic bullae or ulcers pneumococcal sepsis – personal observation

Cryofibrinogenemia AD 144:405–410, 2008; Am J Med 116:332– 337, 2004; Clin Exp Dermatol 25:621–623, 2000; Am J Kidney Dis 32:494–498, 1998; AD 133:1500–1501, 1997; JAAD 24:342–345, 1991; intravascular coagulation necrosis JAAD 25:882–888, 1991 Cryoglobulinemia – mixed cryoglobulinemia – hemorrhagic necrosis, urticaria, ulcers with necrosis, livedo reticularis; intravascular coagulation necrosis JAAD 61:325–332, 2009; NEJM 352:700–707, 2005; JAAD 25:882–888, 1991; necrotic ears BJD 143:1330–1331, 2000; type 1 cryoglobulinemia in multiple myeloma – acral cyanosis, Raynaud’s phenomenon; livedoid necrosis of arms, ears JAMADerm 151:659–660, 2015; type 1 cryoglobulinemia in Waldenstrom’s macroglobulinemia or myeloma Medicine (Balt) 92:61–68, 2013; Am J Med 57:775–788, 1974; monoclonal cryoglobulinemia; cutaneous necrosis JAAD 48:311– 340, 2003; JAAD Case Rep 5:736–738, 2019 Diabetes – microangiopathy, neuropathy NEJM 352:700–707, 2005; dry or wet gangrene; arteriosclerotic peripheral vascular disease; penile gangrene J Urol 132:560–562, 1984 Disseminated intravascular coagulation – personal observation Homocystinuria – cystathionine-beta synthase deficiency; distal cutaneous necrosis Ann DV 126:822–825, 1999 Hyperparathyroidism Hyperphosphatemia J Parent Enteral Nutr 21:50–52, 1997 Hyperviscosity – cryos, paraproteinemia, dehydration Kwashiorkor – personal observation Methylenetetrahydrofolate reductase deficiency – nonuremic calciphylaxis; livedoid necrosis JAAD 69:324–326, 2013; AD 147:450–453, 2011 Oxalosis – acral necrosis with livedo; (primary oxalosis (hyperoxalosis) – type 1 – alanine glyoxylate aminotransferase (transaminase) deficiency; chromosome 2q36–37; type 2 (rare) – D-glyceric acid dehydrogenase deficiency AD 137:957–962, 2001; JAAD 22:952– 956, 1990; AD 131:821–823, 1995; primary hyperoxalosis; necrosis with limb gangrene JAAD 49:725–728, 2003; livedo reticularis, ulcers, and peripheral gangrene AD 136:1272–1274, 2000; autosomal recessive; livedo reticularis, acrocyanosis, peripheral gangrene, ulcerations, sclerodermoid changes (woody induration of extremities), eschar of hand (calcium oxalate); acral and/or facial papules or nodules; end stage renal disease; primary hyperoxalosis – deficiency of alanine:glyoxylate aminotransferase; primary hyperoxalosis – deficiency of D-glycerate dehydrogenase/glyoxylate reductase AD 147:1277–1282, 2011 Paroxysmal nocturnal hemoglobinuria – petechiae, ecchymoses, hemorrhagic bullae; ulcers; red plaques which become hemorrhagic bullae with necrosis; lesions occur on legs, abdomen, chest, nose, and ears; fever; deficiency of enzymes – decay-accelerating factor (DAF) and membrane inhibitor of reactive lysis (MIRL) AD 148:660– 662, 2012; AD 138:831–836, 2002; AD 122:1325–1330, 1986; AD 114:560–563, 1978 Protein C deficiency Blood Coagul Fibrinolysis 9:351–354, 1998; AD 133:1500–1501, 1997; Semin Thromb Hemost 16:299–309, 1990; Blood Coagul Fibrinolysis 1:319–330, 1990; AD 123:1701a-1706a, 1987 Protein S deficiency JAAD 29:853–857, 1993; Semin Thromb Hemost 16:299–309, 1990; Crohn’s disease J Med Vasc 44:291– 294, 2019

Short bowel syndrome – superficial skin necrosis Harefuah 136:855–857, 915, 1999 Sickle-cell anemia – stellate necrosis – personal observation Thrombocythemia – livedo reticularis, acrocyanosis, erythromelalgia, gangrene, pyoderma gangrenosum Leuk Lymphoma 22 Suppl 1:47–56, 1996; Br J Haematol 36:553–564, 1977; AD 87:302–305, 1963; essential thrombocythemia with or without necrotizing vasculitis JAAD 24:59–63, 1991

NEOPLASTIC Atrial myxoma Am J Med 62:792–794, 1977 Basal cell carcinoma NEJM 352:700–707, 2005 CD 30+ lymphoproliferative disorders – red tumors, red plaques with or without necrosis, giant tumor JAAD 72:508–515, 2015 Cutaneous lymphoproliferative disease associated with Epstein-Barr virus – necrotic leg nodule JAAD 57:S69–71, 2007 Eosinophilic histiocytosis JAAD 13:952–958, 1985 Fibrosarcoma/spindle cell sarcoma – necrotic red or violaceous nodule Histiocytic lymphoma (true histiocytic lymphoma) JAAD 50:S9–10, 2004 Infantile myofibromatosis – brown plaque with central necrosis JAAD 71:264–270, 2014 Kaposi’s sarcoma – gangrene and ulcerations of legs JAMA Derm 149:1319–1322, 2013 Keloids – suppurative necrosis Leukemia cutis NEJM 352:700–707, 2005; BJD 143:773–779, 2000;; acute promyelocytic leukemia – necrotic red plaques AD 143:1220–1221, 2007; chronic lymphocytic leukemia – red infiltrated nose with necrosis Cutis 80:208–210, 2007; natural killer cell CD 56- large granular lymphocytic leukemia – necrotic papules and nodules, hydroa vacciniforme-­like lesions JAAD 62:496–501, 2010 Lymphoma – cutaneous T-cell lymphoma NEJM 352:700–707, 2005; JAAD 47:914–918, 2002; tumor necrosis in CTCL JAAD 58:S88–91, 2008; hydroa vacciniforme-like primary CD8+ angiocentric T-cell lymphoma – necrotic facial ulcers Cutis 77:310–312, 2006; primary cutaneous epidermotropic CD8+ T-cell lymphoma – mixture of patches, plaques, papulonodules with central ulceration, necrosis, and hemorrhage JAAD 62:300–307, 2010; hydroa vacciniforme-like cutaneous T-cell lymphoma, Epstein-Barr virus-related – edema, blisters, vesicles, ulcers, scarring, facial scars, swollen nose, lips, and periorbital edema, crusts with central hemorrhagic necrosis, facial dermatitis, photodermatitis, facial edema, facial papules and plaques, crusting of ears, fever JAAD 81:23–41, 2019; JAAD 69:112–119, 2013; primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma – necrotic plaques and nodules JAMADerm 156:155–156, 2020; variant of extranodal NK/T cell lymphoma, nasal type/ CD8+ cytotoxic T cells – recurrent papulovesicles, necrosis, ulceration, facial edema, atrophic scars, lip ulcers, edema of hands, subcutaneous nodules; systemic manifestations; occurs on both sun-exposed and non-sun-exposed skin; necrotic ulcer of hard palate NEJM 371:1629, 2014; Ped Derm 27:463–469, 2010; AD 142:587–595, 2006; BJD 151:372–380, 2004; JAAD 38:574–579, 1998 (angiocentric lymphoma associated with Epstein-Barr virus BJD 147:587–591,

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2002; JAAD 38:574–579, 1998; AD 133:1156–1157, 1997); NK T-cell lymphoma – necrotic plaque JAAD 67:328–330, 2012; subcutaneous panniculitis-­like T-cell lymphoma with necrotic nodules of legs AD 141:1035–1040, 2005; Am J Surg Pathol 15:17–27, 1991; primary cutaneous CD30+ lymphoproliferative disorder (CD8+/CD4+) – necrotic nodule JAAD 51:304–308, 2004; primary B-cell lymphoma – necrotic ulcer of lower back JAAD 55:S24–27, 2006; primary cutaneous epidermotropic aggressive CD8+ T-cell lymphoma – red plaques and nodules with central necrosis (targetoid); ulcerated nodule BJD 173:869–871, 2015; JAAD 67:748–759, 2012

necrotic lip lesions with edema AD 142:651, 2006; BJD 144:874– 877, 2001; AD 118:588–591, 1982

Lymphomatoid papulosis – papules or nodules with central necrosis BJD 172:372–379, 2015; JAAD 70:724–735, 2014; BJD 169:1157–1159, 2013; JAAD 55:903–906, 2006; NEJM 352:700– 707, 2005; JAAD 49:1049–1058, 2003; Am J Dermatopathol 18:221–235, 1996; JAAD 17:632–636, 1987; JAAD 13:736–743, 1985

Acute parapsoriasis (pityriasis lichenoides et varioliformis acuta) (Mucha-Habermann disease) NEJM 361:1787–1796, 2009; JAAD 51:606–624, 2004; JAAD 55:557–572, 2006; AD 123:1335–1339, 1987; AD 118:478, 1982; Dermatol Z 45:42–48, 1925; Arch Dermatol Syph (Wien) 123:586–592, 1916; Veth Dtsch Dermatol Ges 4:495–499, 1894; febrile ulceronecrotic variant of MuchaHabermann disease – papules and plaques with painful ulceration and necrosis Acta DV 94:603–604, 2014; Ped Derm 90:93, 2013; Ped Derm 29:53–58, 2012; Dermatology 225:344–348, 2012; Ped Derm 27:290–293, 2010; JAAD 55:557–572, 2006; NJAAD 54:1113–1114, 2006; Ped Derm 22:360–365, 2005;BJD 152:794– 799, 2005; JAAD 49:1142–1148, 2003; BJD 147:1249–1253, 2002; Ped Derm 8:51–57, 1991; Ann DV 93:481–496, 1966; criteria Int J Dermatol 55:729–738, 2016

Melanoma NEJM 352:700–707, 2005 Metastatic carcinoma – metastatic telangiectatic breast carcinoma – violaceous swelling with telangiectasia and necrosis JAMADerm 155:615–616, 2019 Cutaneous blastic plasmacytoid dendritic cell neoplasm – purple macules, violaceous papules, nodules, tumefactions; highly pigmented dark red, purpuric, necrotic lesions of face, neck JAAD 66:278–291, 2012; ulceronecrotic lesions of scalp; red nodules of back BJD 172:298–300, 2015

Ultraviolet recall manifested as edema, erythema, bullae, hemorrhagic crusting, macules, papules, ulceration, necrosis JAAD 56:494–499, 2007

PRIMARY CUTANEOUS DISEASE Acne fulminans JAAD 77:109–117, 2017 Acne necrotica varioliformis

Degos’ disease – personal observation

Polycythemia vera – ischemic digital necrosis Acta Chir Scand 144:129–132, 1978

Erythema elevatum diutinum BJD 67:121–145, 1955

Squamous cell carcinoma NEJM 352:700–707, 2005

Pityriasis rosea – vesicular variant

Thrombocythemia SKINMed 17:204–205, 2019; Am J Dermatopathol 39:637–662, 2017

Pustular psoriasis

Necrolytic acral erythema - hepatitis C-related

Pyoderma faciale Subcutaneous fat necrosis of newborn

PARANEOPLASTIC DISORDERS Choriocarcinoma – acne fulminans in prepubertal boy – personal observation Type 1 cryoglobulinemia – with myeloma; livedo racemosa (necrotizing livedo reticularis) J Drugs Dermatol 13:498–499, 2014 Hypersensitivity to mosquito bites – associated with lymphoma/ leukemia BJD 153:210–212, 2005; JAAD 45:569–578, 2001; BJD 138:905–906, 1998 Necrolytic migratory erythema (glucagonoma syndrome) – necrotic crusted plaques of legs Int J Dermatol 57:642–645, 2018; BJD 174:1092–1095, 2016 Paraneoplastic acral vascular syndrome – acral cyanosis and gangrene JAAD 47:47–52, 2002; AD 138:1296–1298, 2002

PSYCHOCUTANEOUS DISORDERS Factitial dermatitis – linear lesions Ped Derm 21:205–211, 2004; JAAD 1:391–407, 1979; penile gangrene (Munchhausen syndrome) – ulcerated nodules; necrosis of legs; injection of paint thinner JAAD 71:376–381, 2014; Lancet 1:339–341, 1951; patchy areas of necrosis Ped Derm 32:604–608, 2015;

SYNDROMES Anterior tibial syndrome (compartment syndrome) Surg Clin NA 63:539–565, 1983

Pyoderma gangrenosum, atypical (bullous) – associated with myeloproliferative disease

Antiphospholipid antibody syndrome – eschar and ulceration NEJM 352:700–707, 2005; JAAD 47:766–769, 2002; NEJM 346:752–763, 2002; Semin Arthritis Rheum 31:127–132, 2001; JAAD 36:149–168, 1997; JAAD 36:970–982, 1997; Clin Rheumatol 15:394–398, 1996; South Med J 88:786–788, 1995; BJD 120:419–429, 1989; nasal tip necrosis BJD 142:1199–1203, 2000; neonatal digital gangrene AD 143:121–122, 2007; acral livedo and necrosis AD 147:164–167, 2011; lupus anticoagulant

Sweet’s syndrome with myelodysplasia – necrotic bullae BJD 178:595–602, 2018

Behcet’s disease (bullous necrotizing vasculitis) JAAD 21:327–330, 1989; pyoderma gangrenosum-like lesions JAAD 40:1–18, 1999

Venous thrombosis

Familial chilblain lupus – paronychia, acral erythema, acral papules, necrotic ulcers, facial ulcers, mutilation of fingers, ear lesions; mutation of exonuclease III domain of 3′ repair exonuclease 1 (TREX1) JAMADerm 151:426–431, 2015

Paraneoplastic pemphigus – necrosis of eyelids and oral mucosa Paraneoplastic vasculitis with myelodysplasia – personal observation Paraneoplastic venous thrombosis

PHOTODERMATITIS Hydroa vacciniforme – vesiculopapular eruption of face; crusted papules, necrosis, facial ulcers BJD 173:801–805, 2015;

Flood syndrome – sudden rush of ascitic fluid with spontaneous rupture of umbilical hernia in longstanding ascites and end stage liver disease JAAD Case Reports 2015:1:5–6

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Hypereosinophilic syndrome – cutaneous necrotizing eosinophilic vasculitis with Raynaud’s phenomenon BJD 143:641–644, 2000; hypereosinophilic syndrome associated with T-cell lymphoma JAAD 46:S133–136, 2002; fingertip necrosis with vasculitis AD 132:535– 541, 1996; digital necrosis without vasculitis BJD 144:1087–1090, 2001; cutaneous infarction BJD 148:817–820, 2003; JAAD 5:1041–1044, 2019

  Hydrofluoric acid   Lime dust – necrosis with ulcers Contact Dermatitis 1:59, 1981  Phenol  Phosphorus

IgG4-related disease – cutaneous plasmacytosis (papulonodules); pseudolymphoma; angiolymphoid hyperplasia with eosinophilia; Mikulicz’s disease; psoriasiform dermatitis; morbilliform eruption; hypergammaglobulinemic purpura; urticarial vasculitis; ischemic digits; Raynaud’s disease and digital gangrene BJD 171:929,959–967, 2014

Cold – central facial necrosis after application of cold pack during cardiac surgery – personal observation

Infantile myofibromatosis Ped Derm 5:37–46, 1988 Kawasaki’s disease – erythema, crusting, or necrosis of BCG inoculation sites JAAD 69:501–510, 2013; peripheral gangrene JAAD 69:501–510, 2013 Neurofibromatosis type I – vasculopathy with acral necrosis, livedoid painful ulcerations BJD 172:253–256, 2015; Pediatrics 100:395– 397, 1997 POEMS syndrome – vasculitis with necrosis Clin Rheumatol 26:1989–1992, 2007; calciphylaxis Orphanet J Rare Dis April 12, 2016 RACAND syndrome – acral or digital necrosis; Raynaud’s phenomenon, anticentromere antibodies and necrosis of digits without sclerodactyly and sclerosis of internal organs JAAD 43:621, 2001 Rowell’s syndrome – lupus erythematosus and erythema multiforme-like syndrome – papules, annular targetoid lesions, vesicles, bullae, necrosis, ulceration, oral ulcers; perniotic lesions JAAD 21:374–377, 1989 SAPHO syndrome – palmoplantar pustulosis with sternoclavicular hyperostosis; non-palmoplantar pustulosis, acne fulminans, acne conglobata, hidradenitis suppurativa, psoriasis, multifocal osteitis Cutis 71:63–67, 2003; Cutis 62:75–76, 1998; Rev Rheum Mol Osteoarthritic 54:187–196, 1987; Ann Rev Rheum Dis 40:547–553, 1981; with neutrophilic dermatosis (ulceronecrotic bullous Sweet’s syndrome) AD 143:275–276, 2007 Sjogren’s syndrome – nail-fold infarcts, gangrene of fingers Sweet’s syndrome – necrotizing Sweet’s syndrome presenting as necrotizing fasciitis JAMADerm 155:79–84, 2019; Int J Rheum Dis 20:2197–2199, 2017 Thoracic outlet obstruction AD 138:1296–1298, 2002 Werner’s syndrome – acral necrosis Medicine 45:177–221, 1966 Wiskott-Aldrich syndrome

TOXINS Carbon monoxide poisoning – endothelial cell damage; compartment syndrome, pressure necrosis, rhabdomyolysis Pediatr 68:215–224, 1981

TRAUMA Blunt trauma – repetitive blunt trauma AD 138:1296–1298, 2002 Carpal tunnel syndrome Chemical burns   Acids and alkalis   Cement (calcium hydroxide) BJD 102:487–489, 1980; Br Med J i:1250, 1978   Chromic acid

Chilblains – fingertips and toetips; with necrosis on fingers, toes, nose, and ears in patients with monocytic leukemia AD 121:1048, 1052, 1985

Coma bullae – sweat gland necrosis Am J Dermatopathol 35:381– 384, 2013; Ann DV 122:780–782, 1995 Compartmental syndrome (crush injury of thorax) – skin necrosis Condom catheter – gangrene of glans or shaft of penis JAMA 244:1238, 1980 Crush injury of fingertip AD 138:1296–1298, 2002 Cryosurgery JAAD 8:513–519, 1983 Electric shock – fingertip necrosis AD 138:1296–1298, 2002 External compression of arterial supply (popliteal entrapment, cervical rib) Frostbite – vesicles, bullae, ischemic necrosis; calcification; congenital frostbite – acral necrosis Ped Derm 26:625–626, 2009 Gentian violet Acta DV 52:55–60, 1972 Heel sticks of neonate – gangrene of heel Hypothenar hammer syndrome AD 138:1296–1298, 2002 Intravenous drug addiction – dorsal vein of penis; necrosis BJD 150:1–10, 2004; Cutis 29:62–72, 1981 “Krokodil” – injectable opiate; cooking cocaine with caustic chemicals; described in Russia since 2002; flesh-eating necrosis; possible first cases in Arizona in 2013 Clin Inf Dis 57:ii, 2013 Laser burns Microwave radiation burns Nerve injury, traumatic – small areas of acral necrosis Negative pressure device for erectile impotence J Urol 146:1618– 1619, 1991; penile ring; hair tourniquet; Fournier’s gangrene Nicolau syndrome – livedoid aseptic necrosis after injections; iatrogenic cutaneous necrosis; “embolia cutis medicamentosa” Am J Dermatopathol 40:212–215, 2018; JAAD 54:S241–242, 2006 Orthopedic braces Injury 25:323–324, 1994 Oxygen face mask with continuous positive pressure Anaesthesia 48:147–148, 1993 Penile gangrene – post-surgical; calciphylaxis Clin Exp Dermatol 43:645–647, 2018 Physical trauma- rock drillers, lumberjacks, riveters, grinders, pneumatic hammer operators Post-surgical – penile gangrene Pressure necrosis NEJM 352:700–707, 2005; due to continuous positive pressure ventilation Ped Derm 29:45–48, 2012 Pulse oximetry – acral necrosis Cutis 48:235–237, 1991; Anesth Analg 67:712–713, 1988 Radial or ulnar artery cannulation AD 138:1296–1298, 2002; N Y State J Med 90:375–376, 1990 Radiation dermatitis, acute or chronic – necrosis JAAD 54:28–46, 2006; NEJM 352:700–707, 2005; J Laryngol Otol 112:1142–1146, 1998; necrosis after fluoroscopy during coronary angioplasty AD 139:140–142, 2003 Skin popping Clin Nucl Med 22:865–866, 1997 Surgery – pressure necrosis of scalp, hips, occipital scalp

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Surgical embolization – occipital scalp necrosis and scarring Surg Neurol 25:357–366, 1988

Degos’ disease (malignant atrophic papulosis) BJD 100:21–36, 1979; Ann DV 79:410–417, 1954

Thoracic outlet obstruction – cervical rib, external compression of arterial supply AD 138:1296–1298, 2002

Dialysis shunt-associated steal syndrome Ann Dermatol Venereol 133:264–267, 2006; Curr Surg 63:130–136, 2006; AD 138:1296– 1298, 2002

Tourniquet injury (hair) – penile gangrene Traumatic disruption of arterial wall Trench foot, immersion foot – superficial gangrene Clin Exp Dermatol 45:10–14, 2020

VASCULAR Acral necrotic livedo reticularis – surgical acrylic cement embolus following vertebroplasty BJD 156:382–383, 2007 Acute hemorrhagic edema of infancy – purpura in cockade pattern of face, cheeks, eyelids, and ears; may form reticulate pattern; edema of penis and scrotum JAAD 23:347–350, 1990; necrotic lesions of the ears, urticarial lesions; oral petechiae JAAD 23:347– 350, 1990; Ann Pediatr 22:599–606, 1975; edema of limbs and face Cutis 68:127–129, 2001; AD 133:1500–1501, 1997 ANCA-associated vasculitis with acquired protein S deficiency Throm Haemost 84:929–930, 2000 Aneurysm – dissecting aneurysm, thrombosed aneurysm Angiopericytomatosis (angiomatosis with cryoproteins) – painful red papules and ulcerated plaques acrally; necrotic plaques JAAD 49:887–896, 2003 Arterial fibromuscular dysplasia – fingertip necrosis AD 138:1296– 1298, 2002 Arteriovenous fistulae – vascular steal syndrome in hemodialysis patients (dialysis-associated steal syndrome) with arteriovenous fistulae JAAD 58:888–891, 2008; AD 138:1296–1298, 2002 Atherosclerosis – ischemic necrosis, gangrene; leg ulcers with small areas of necrosis along margin NEJM 363:2651, 2010 AD 138:1296–1298, 2002 Atrophie blanche (livedoid vasculopathy) JAAD 69:1033–1042, 2013; AD 119:963–969, 1983 Benign (reactive) angioendotheliomatosis – red-brown or violaceous nodules or plaques with small areas of necrosis JAAD 38:143–175, 1998 Brachiocephalic thrombosis – breast necrosis – personal observation Eosinophilic granulomatosis with polyangiitis Autoimmunol Rev 14:341–348, 2015; AD 139:715–718, 2003; JAAD 48:311–340, 2003; JAAD 47:209–216, 2002; JAAD 37:199–203, 1997; JAAD 27:821–824, 1992; JID 17:349–359, 1951; Am J Pathol 25:817, 1949; necrotic purpura of scalp Ann DV 122:94–96, 1995; umbilicated nodules with central necrosis of elbows and knees (papulonecrotic lesions) JAAD 48:311–340, 2003; BJD 127:199–204, 1992; skin infarcts BJD 150:598–600, 2004; Mayo Clinic Proc 52:477–484, 1977; presenting as purpura fulminans Clin Exp Dermatol 29:390– 392, 2004; cutaneous infarcts Autoimmun Rev 14:341–348, 2015; Dermatopathol 37:214–221, 2015; JAAD 37:199–203, 1997; JAAD 47:209–216, 2002; JID 17:349–359, 1951; Am J Pathol 25:817, 1949 Cholesterol emboli JAMADerm 150:903–905, 2014; J Dermatol Case Rep 24:27–29, 2009 Cutaneous polyarteritis nodosa – atrophie blanche lesions, acrocyanosis, Raynaud’s phenomenon, peripheral gangrene, red plaques and peripheral nodules, myalgias; macular lymphocytic arteritis – red or hyperpigmented reticulated patches of legs JAAD 73:1013–1020, 2015

Diffuse dermal angiomatosis of the breast Clin Exp Dermatol 45:107–109, 2020; Int J Dermatol 53:445–449, 2014 Disseminated intravascular coagulation (DIC) – intravascular coagulation necrosis; associated with sepsis, snake envenomation, amniotic fluid embolization, fat emboli, abruption placentae, severe head injury, Kasabach-Merritt syndrome JAAD 61:325–332, 2009; JAAD 25:882–888, 1991; peripheral symmetric gangrene AD 137:139–140, 2001 Emboli – tumor; intravascular coagulation necrosis; cholesterol emboli – peripheral gangrene JAAD 55:786–793, 2006; BJD 146:511–517, 2002; Medicine 74:350–358, 1995; JAAD 25:882– 888, 1991; Angiology 38:769–784, 1987; AD 122:1194–1198, 1986; Angiology 37:471–476, 1986; septic NEJM 352:700–707, 2005 Erythromelalgia – associated with thrombocythemia – may affect one finger or toe; ischemic necrosis JAAD 22:107–111, 1990 Glomeruloid angioendotheliomatosis – red purpuric patches and acral necrosis – associated with cold agglutinins JAAD 49:887–896, 2003 Granulomatosis with polyangiitis – acneiform facial and truncal lesions with crusted necrotic papules, ulcers; palpable purpura JAAD 72:859–867, 2015; cutaneous necrosis NEJM 352:700–707, 2005; papulonecrotic lesions JAAD 48:311–340, 2003; Cutis 64:183–186, 1999; JAAD 31:615–622, 1994; necrotic penile ulcers Clin Rheumatol 17:239–241, 1998; JAAD 31:605–612, 1994; AD 130:1311–1316, 1994; genital and perineal necrosis Am J Med 108:680–681, 2000; necrotic lesion of forehead Ped Derm 16:277–280, 1999; herpetiform necrotic purpuric papules over joints (ankles, elbows) AD 148:849–854, 2012 Granulomatous vasculitis, cutaneous – necrosis with ulcers JAAD 58:S93–95, 2008; breast necrosis, livedo reticularis, arthralgias Rev Med Brux 33:112–115, 2012 Hemangioma (proliferating hemangioma) – focal necrosis Henoch-Schonlein purpura Ped Derm 15:357–359, 1998; Ped Derm 12:314–317, 1995; Am J Dis Child 99:833–854, 1960; in the adult AD 125:53–56, 1989 Heterozygous factor V Leiden deficiency BJD 143:1302–1305, 2000 Hypertensive ulcer (Martorell’s ulcer) – starts as area of cyanosis with progression to ulcer of lower lateral leg with livedo at edges Phlebology 3:139–142, 1988 Hypotension Intravascular thrombosis – DIC (meningococcemia, Rocky Mountain spotted fever, fungal, parasitic (Strongyloides)), atheroemboli, fat emboli, calciphylaxis, coumarin necrosis, protein C or S deficiency, antithrombin III deficiency, purpura fulminans, antiphospholipid antibody syndrome, thrombotic vasculitis (LE), cryoglobulins, cryofibrinogens, oxalosis Ischemic limb gangrene with pulses NEJM 373:642–655, 2015   Antiphospholipid antibody syndrome   Cardiogenic shock   Congenital hypercoagulability   Disseminated intravascular coagulation   Deep vein thrombosis in an ischemic limb   Heparin-induced thrombocytopenia (HIT)   Metastatic adenocarcinoma   Septic shock (meningococcemia)   Venous limb gangrene

698 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Ischemic venous thrombosis (phlegmasia cerulae dolens) (venous gangrene) JAAD 28:831–835, 1993; AD 123:933–936, 1987 Juvenile gangrenous vasculitis of the scrotum Kasabach-Merritt syndrome – personal observation Livedoid vasculopathy NEJM 352:700–707, 2005; livedoid vasculopathy associated with anti-phosphatidylserine-­prothrombin complex antibody – acral gangrene, foot ulcers AD 147:621–623, 2011 Lymphomatoid granulomatosis – destruction of midline nasal structures; necrotic plaque of nose; crateriform nodule of cheek JAMADerm 155:113–114, 2019 Neonatal gangrene – secondary to umbilical arterial catheterizations, polycythemia, prematurity BJD 150:357–363, 2004 Perinatal gangrene of the buttock, scrotum, and prepuce AD 121:23–24, 1985 Peripheral vascular disease – personal observation Polyarteritis nodosa – livedoid necrosis NEJM 352:700–707, 2005; peripheral embolization of thrombi with necrosis of fingers or toes cutaneous – peripheral gangrene Ped Derm 15:103–107, 1998; Ann Rheum Dis 54:134–136, 1995; JAAD 31:54–56, 1994; palpable purpura, livedo, nodules, urticaria, skin necrosis with ulcers BJD 159:615–620, 2008; JAAD 48:311–340, 2003; petechiae or gross hemorrhage JAAD 31:561–566, 1994; cutaneous infarcts presenting as purpuric plaques; microscopic polyarteritis nodosa – arthralgias, leg ulcers, fever, livedo, nodules, urticaria, palpable purpura, petechiae, ecchymoses, acral bullae, plantar red plaque JAAD 73:1013–1020, 2015; BJD 159:615–620, 2008; JAAD 57:840–848, 2007; Eur J Dermatol 14:255–258, 2004; microscopic polyarteritis nodosa – hemorrhagic papules (palpable purpura) JAAD 48:311– 340, 2003; AD 128:1223–1228, 1992; oral purpura Oral Surg 56:597–601, 1983; cutaneous (livedo with nodules) – purpura; painful or asymptomatic red or skin colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk BJD 146:694–699, 2002; splinter hemorrhages; childhood cutaneous polyarteritis nodosa – acral extremity necrosis; fever, muscle weakness and myalgia, and livedo with necrosis (livedo racemosa) BJD 171:201–202, 2014; Ped Derm 29:473–478, 2012 Porcelain aorta – chest necrosis – personal observation Purpura fulminans JAAD 57:944–956, 2007; Semin Thromb Hemost 16:333–340, 1990; Br Med J 2:8–9, 1891; neonatal AD 123:1701a-1706a, 1987; neonatal purpura fulminans – ecchymoses of limbs at sites of pressure in first day of life; enlarge rapidly, hemorrhagic bullae with central necrosis; homozygous protein C or protein S deficiency Semin Thromb Hemost 16:299–309, 1990 Pustular vasculitis – annular pustular plaques with central necrosis

Sickle-cell infarct – thrombotic vasculitis Small vessel occlusive arterial disease – diabetes NEJM 352:700– 707, 2005 Symmetric peripheral gangrene Cutis 46:53–55, 1990  Primary arterial disease – polyarteritis nodosa, SLE, rheumatoid arthritis, arteriosclerosis obliterans, thromboangiitis obliterans   Congestive heart failure  Overwhelming infection – meningococcemia, pneumococcal, rickettsial, viral, fungal, other  Miscellaneous – carbon monoxide poisoning, fibrin thrombi, cold injury, crutch pressure arteritis   Mitral stenosis with or without left atrial wall thrombus   Embolization – cholesterol, infectious, tumor, thromboembolic   Myocardial infarction   Pulmonary embolus   Vasospastic – ergotism, Raynaud’s   Primary venous disease – venous gangrene Syphilitic aortic aneurysm eroding through the sternum Dur M Cardiothorac Surg 10:922–924, 1996 Takayasu’s arteritis – cutaneous necrotizing vasculitis NEJM 352:700–707, 2005; Dermatology 200:139–143, 2000 Temporal arteritis (giant cell arteritis) – headache, loss of vision, tender temporal artery, muscle or joint pain, malaise, weight loss, loss of appetite, jaw claudication, tongue necrosis, absent temporal pulses JAAD 61:701–706, 2009; Arthritis Rheum 42:1296, 1999; bilateral forehead necrosis with linear eschars JAAD 63:343–344, 2010; with scalp necrosis JAAD 61:701–706, 2009; AD 143:1079– 1080, 2007; Clin Rheumatol 26:1169, 2007; BJD 120:843–846, 1989; Q J Med 15:47–75, 1946; gangrene of leg, tongue necrosis BJD 151:721–722, 2004; BJD 76:299–308, 1964; ulcer of scalp; scalp necrosis; giant cell arteritis due to nivolumab JAMADerm 155:1086–1087, 2019; lip necrosis J Oral Maxillofac Surg 51:581– 583, 1993; scalp necrosis J Neuro Ophthalmol Oct 15, 2019 Thromboangiitis obliterans (Buerger’s disease) Am J Med Sci 136:567–580, 1908 Thromboembolic phenomena – fingertip necrosis; cardiac source, arterial source, aneurysm (subclavian or axillary arteries), infection, hypercoagulable state AD 138:1296–1298, 2002 Thrombotic thrombocytopenic purpura Thrombotic vasculitis – personal observation Thrombosis of large vessels Urticarial vasculitis Clin Rev Allergy Immunol 23:201–216, 2002 Vasculitis – large and/or small vessel – leukocytoclastic vasculitis NEJM 352:700–707, 2005; AD 134:309–315, 1998;

Radial artery removal for coronary bypass grafting AD 138:1296– 1298, 2002

urticarial vasculitis AD 134:231–236, 1998; Cutaneous small vessel vasculitis – ulcerated purpuric necrotic plaques AD 148:887–888, 2012

Raynaud’s phenomenon

Vasoconstriction

Reactive angioendotheliomatosis – red purple-purpuric patches and plaques with necrotic ulcers; includes acroangiomatosis, diffuse dermal angiomatosis, intravascular histiocytosis, glomeruloid angioendotheliomatosis, angiopericytomatosis (angiomatosis with luminal cryoprotein deposition), reactive angiomatosis-like reactive angioendotheliomatosis; associated with subacute bacterial endocarditis, hepatitis, cholesterol emboli, cryoglobulinemia, arteriovenous shunt, anti-phospholipid antibody syndrome, chronic lymphocytic leukemia, monoclonal gammopathy, chronic renal failure, rheumatoid arthritis, severe peripheral vascular disease, arterio-venous fistulae JAAD 49:887–896, 2003; BJD 147:137–140, 2002; JAAD 42:903–906, 2000

Venous stasis ulceration (chronic venous insufficiency) – medial lower leg and medial malleolus NEJM 352:700–707, 2005; AD 133:1231–1234, 1997; Semin Dermatol 12:66–71, 1993; with subcutaneous calcification J Derm Surg Oncol 16:450–452, 1990

Recurrent cutaneous eosinophilic necrotizing vasculitis – papules, purpura, necrosis Acta DV 80:394–395, 2000

Venous limb gangrene (phlegmasia cerulea dolens) – during warfarin treatment of cancer-associated deep venous thrombosis; due to severe depletion of protein C and failure to reduce thrombin generation Ann Int Med 135:589–593, 2001; massive proximal venous thrombosis resulting in arterial insufficiency; triad of asymmetric leg edema, hemorrhagic bullae, cyanosis, acral necrosis, pain NEJM 370:1742–1748, 2014 Congenital Volkmann ischemic contracture (neonatal compartment syndrome) – upper extremity circumferential contracture

Neural Tube Dysraphism from wrist to elbow; necrosis, cyanosis, edema, eschar, bullae, purpura; irregular border with central white ischemic tissue with formation of bullae, edema, or spotted bluish color with necrosis, a reticulated eschar or whorled pattern with contracture of arm; differentiate from necrotizing fasciitis, congenital varicella, neonatal gangrene, aplasia cutis congenital, amniotic band syndrome, subcutaneous fat necrosis, epidermolysis bullosa or protein C or S deficiency with disseminated intravascular coagulation; asymmetric, well-demarcated, stellate ulcers of arms with neuromuscular defects; in newborn; serpiginous border; muscle necrosis and nerve palsy due to increased intracompartmental pressure from amniotic band, oligohydramnios, or abnormal fetal position; begins as large bulla Ped Derm 37:207– 208, 2020; JAMADerm 150:978–980, 2014; Ped Derm 25:352– 354, 2008; BJD 150:357–363, 2004

NEURAL TUBE DYSRAPHISM Ped Derm 32:161–170, 2015 Acrochordon, pseudotail, or true tail Aplasia cutis and congenital Anterior cephalocele – intranasal polypoid lesion, broad nasal root, soft compressible nodule of nose Cephaloceles – overlying hypertrichosis, capillary malformation, or hair collar Dermoid cysts and sinuses – broad nasal root; yellow plaque; skin colored nodule; pits Lipoma Lumbosacral stigmata – lipoma, acrochordon, pseudotail, true tail, aplasia cutis congenital and scars, dermoid cyst or sinus, infantile hemangioma >2.5 cm, atypical dimple, infantile hemangioma female; neck>extremities>viscera; solitary; affects skin, bone, soft tissues; generalized myofibromatosis with visceral involvement   Infantile fibrosarcoma – in first year of life; male>female; deep tissues of extremities; large solitary red painless dome shaped 10–15 cm tumor; vascular and ulcerated appearance; metastases uncommon

Apocrine gland carcinoma – axillary mass Am J Med 115:677–679, 2003

Folliculosebaceous cystic hamartoma – multilobulated lesion of nose The Dermatologist April 2018:47–50

NEOPLASTIC DISEASES Acrochordon, giant Aggressive digital papillary adenocarcinoma – exophytic friable multilobulated tumor JAAD 60:331–339, 2009 Angiomyofibroblastoma of vulva Ginecol Obstet Mex 81:345–348, 2013 Angiomyxomas AD 144:1217–1222, 2008

720 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Ganglion cyst overlying acromioclavicular joint – verrucous multilobulated tumor JAAD 64:1206–1208, 2011; AJR Roentgenol 178:1445–1449, 2002 Giant cell fibroblastoma JAMADerm 150:323–324, 2014 Giant cell tumor of soft tissue Cutis 93:278, 286–288, 2014 Giant cell tumor of the tendon sheath – multilobulated single or multiple JAAD 43:892, 2000; nodules of the fingers J Dermatol 23:290–292, 1996; J Bone Joint Surg Am 66:76–94, 1984 Giant folliculosebaceous cystic hamartoma – multinodular plaque of scalp AD 141:1035–1040, 2005 Hibernoma – giant multilobulated tumor of neck NEJM 367:1636, 2012 Infantile digital fibromatosis – pink multilobulated nodule of toe Ped Dem 26:347–348, 2009 Intradermal nevus, lobulated JAAD 24:74–77, 1991 Kaposi’s sarcoma – keloidal Kaposi’s sarcoma JAAD 59:179–206, 2008; AD 141:1311–1316, 2005; BJD 145:847–849, 2001; JAAD 38:143–175, 1998; Dermatology 190:324–326, 1995; keloidal Kaposi’s sarcoma Dermatology (Basel) 189:271–274, 1994; lymphangioma-like variant of KS AD 139:381–386, 2003 Keloids J Drugs Dermatol 10:468–480, 2011; Ped Derm 24:280– 284, 2007;; keloids in Ehlers-Danlos syndrome, progeria, Rubinstein-Taybi syndrome Ped Derm 12:387–389, 1995; plantar keloid JAAD 48:131–134, 2003 Keratoacanthoma JAAD 19:826–830, 1988; keratoacanthoma centrifugum marginatum BJD 163:633–637, 2010 Leiomyosarcoma Ped Derm 26:477–479, 2009; J D Surg Oncol 9:283–287, 1983 Leukemia cutis, including congenital leukemia cutis JAAD 34:375– 378, 1996; chronic lymphocytic leukemia – multilobulated helices AD 147:1443–1448, 2011; acute myelogenous leukemia – mountain range lesions with leonine facies Cutis 102:266,271–272, 2018 Lipoblastomatosis Ped Derm 23:152–156, 2006 Lipomas, multiple Lymphocytoma cutis Lymphoma – cutaneous T-cell lymphoma JAAD 70:205–220, 2014;; JAAD 25:345–349, 1991; HTLV-1 (keloid-like) JAAD 34:69–76, 1996; cutaneous type adult T-cell leukemia/lymphoma – multilobulated giant purple tumor JAAD 57:S115–117, 2007; pilotropic (follicular) CTCL AD 138:191–198, 2002; gamma/delta T cell lymphoma AD 136:1024–1032, 2000; CD30+ lymphoma of AIDS; primary cutaneous follicle center lymphoma JAAD 69:343–354, 2013; JAAD 64:135–143, 2011; AD 143:1520–1526, 2007; BJD 157:1205–1211, 2007; cutaneous B-cell lymphoma – multilobulated red nodules BJD 177:287–289, 2017; Cutis 94:3217,249–251, 2014; B-cell lymphoma JAAD 29:359–362, 1993; JAAD 16:518–526, 1987; large B-cell lymphoma BJD 149:542–553, 2003; primary cutaneous large B-cell lymphoma of the legs BJD 159:145–151, 2008; AD 132:1304–1308, 1996; primary cutaneous marginal zone B-cell lymphoma AD 145:1183–1188, 2009; reticulohistiocytoma of the dorsum (B-cell lymphoma) JAAD 18:259–272, 1988; primary cutaneous epidermotropic CD8+ T-cell lymphoma – mixture of patches, plaques, papulonodules with central ulceration, necrosis, and hemorrhage JAAD 62:300–307, 2010; primary cutaneous follicle center lymphoma with diffuse CD 30 expression – papules, plaques, nodules, multilobulated scalp tumor JAAD 71:548–554, 2014; Burkitt’s lymphoma – multiple subcutaneous mountain range nodules JAAD 64:1196–1197, 2011;; primary cutaneous follicle center cell lymphoma – multilobulated nodules, red plaques of scalp, nodules of head and neck,

papules of head and neck JAAD 70:1010–1020, 2014; extranodal NK/T-cell lymphoma, nasal type – multilobulated giant tumor of leg JAMADerm 150:1109–1110, 2014; Epstein-Barr virus associated plasmablastic lymphoma (HIV-­defining lesion) – ulcerated fungating giant perianal tumor Cutis 103:328,333–334, 2019; BJD 174:398–401, 2016 Malignant blue nevus; JAAD 19:712–722, 1988 Malignant fibrous histiocytoma Malignant histiocytosis X Cancer 54:347–352, 1984 Malignant proliferating trichilemmal tumor BJD 150:156–157, 2004; of scalp Indian J Surg 78:493–495, 2016 Melanocytic nevus – giant congenital melanocytic nevi with benign proliferative nodules BJD 176:1131–1143, 2017; AD 140:83–88, 2004; atypical proliferative nodules in congenital melanocytic nevi of scalp BJD 165:1138–1142, 2011 Melanoma Curr Prob Derm 14:41–70, 2002; Cutis 69:353–356, 2002; Semin Oncol 2:5–118, 1975; polypoid melanoma JAAD 23:880–884, 1990; animal type melanoma AD 145:55–62, 2009; amelanotic melanoma arising in large congenital melanocytic nevus – multilobulated vascular nodule JAAD 68:913–925, 2013; anal mucosal melanoma – perianal multilobulated skin colored nodule Cutis 89:112, 116, 2012; amelanotic melanoma – multilobulated red nodules of lower lip Cutis 92:250– 252, 2013 Melanoma of the soft parts (clear cell sarcoma) JAAD 38:815–819, 1998 Merkel cell carcinoma – multilobulated red nodules of scalp AD 145:494–495, 2009; of nose AD 149:501–502, 2013 Metastases – carcinoma telangiectoides; lung cancer with emboli in pulmonary venous circulation; nodules of scalp resembling cylindromas; Cancer 19:162–168, 1966; cutaneous metastases (adenocarcinoma) – lymphangioma-like lesions JAAD 30:1031– 1032, 1994; metastatic prostate carcinoma mimicking cylindromas JAAD 33:161–182, 1995; rhinophyma-like metastatic carcinoma Cutis 57:33–36, 1996; breast carcinoma; Sister Mary Joseph nodule – multilobulated nodule of umbilicus; metastatic gastric adenocarcinoma Cutis 85:90–92, 2010 Mucinous carcinoma of skin JAAD 49:941–943, 2003; JAAD 36:323–326, 1997 Mucinous nevus (connective tissue hamartoma) AD 141:897–902, 2005 Multiple myeloma – multinodular violaceous fungating tumor JAAD 74:878–884, 2016 Myofibroma – personal observation Myxoid dermatofibrosarcoma protuberans – multilobulated or sessile nodule AD 147:857–862, 2011 Nerve sheath myxoma AD 145:195–200, 2009 Neural fibrolipoma AD 135:707–712, 1999 Neuroectodermal tumors – multiple primitive neuroectodermal tumors JAAD 31:356–361, 1994 Neurofibroma – diffuse neurofibroma JAAD 48:938–940, 2003; plexiform neurofibroma Neurogenic sarcoma Nevus lipomatosis superficialis – mountain range-like lesions Ped Derm 37:352–354, 2020; BJD 156:380–381, 2007; Cutis 72:237– 238, 2003; AD 128:1395–1400, 1992 Nevus sebaceous – personal observation Nevus sebaceous with tubular apocrine adenoma and syringocystadenoma papilliferum – velvety, grouped nodules of breast BJD 156:1397–1399, 2007; trichoblastoma, basal cell carcinoma,

Nodules, Multilobulated eccrine poroma, sebaceous carcinoma, leiomyosarcoma, syringocystadenoma papilliferum Pilomatrixoma Plaque-like myofibroblastic tumor of infancy – multinodular red-brown plaque Ped Derm 34:176–179, 2017 Plasmacytoma – trauma-induced secondary cutaneous plasmacytoma AD 146:1301–1306, 2010 Pleomorphic fibrohistiocytoma – personal observation Plexiform schwannoma of the foot Eur Radiol 9:1653–1655, 1999 Polymorphous sweat gland carcinoma JAAD 46:914–916, 2002 Primary cutaneous alveolar rhabdomyosarcoma – annular multinodular mass of chest Ped Derm 37:184–186, 2020 Primitive myxoid mesenchymal tumor of infancy – multilobulated plaque/tumor Ped Derm 27:635–637, 2010; differential diagnosis includes rhabdomyosarcoma, infantile desmoids fibromatosis, fibromyxoid sarcoma, low grade myofibrosarcoma, congenital infantile fibrosarcoma Proliferative fasciitis SKINmed 12:111–112, 2014 Proliferating pilar cyst JAAD 69:849–850, 2013; Cutis 48:49–52, 1991 Regressing atypical histiocytosis AD 126:1609–1616, 1990 Rhabdomyomatous mesenchymal hamartoma – papillomatous lesion Ped Derm 32:256–262, 2015 Alveolar rhabdomyosarcoma, metastatic red multinodular ulcerated plaque Ped Derm 33:225–226, 2016 Congenital rhabdomyosarcoma – multilobulated cobblestoned nodule of bridge of nose Ped Derm 36:747–749, 2019 Salivary pleomorphic adenoma Cutis 63:167–168, 1999 Malignant schwannoma – personal observation

721

PARANEOPLASTIC DISORDERS Necrobiotic xanthogranuloma with paraproteinemia JAAD 52:729– 731, 2005

PRIMARY CUTANEOUS DISEASES Acne conglobata JAAD 62:861–863, 2010 Acne keloidalis JAAD 56:699–701, 2007 Acne rosacea – rhinophyma NEJM 367:1838, 2012 Cutis verticis gyrata – acromegaly, Apert syndrome, amyloidosis, leukemia, myxedema, syphilis, pachydermoperiostosis, tuberous sclerosis Cystic acne – exophytic abscesses of chin in follicular occlusion triad JAAD 48:S47–50, 2003 Endometriosis (villar nodule) – umbilical multilobulated red nodule AD 148:1331–1332, 2012 Erythema elevatum diutinum JAMADerm 153:315–316, 2017; BJD 143:415–420, 2000; keloid-like lesions of erythema elevatum diutinum in AIDS AD 144:933–938, 2008; JAAD 28:919–922, 1993 Follicular mucinosis JAAD 20:441–446, 1989 Granuloma annulare, including subcutaneous granuloma annulare Hailey-Hailey disease – vegetative multilobulated malodorous friable plaques of cheek JAAD 65:223–224, 2011 Lichen simplex chronicus – personal observation Myospherulosis (subcutaneous spherulocystic disease) – multilobulated abdominal nodule AD 138:1309–1314, 2002 Periumbilical pseudoxanthoma elasticum JAAD 39:338–344, 1998 Pseudofolliculitis barbae with keloids

Sclerotic fibroma – personal observation Sebaceous carcinoma Cutis 91:169,175–176, 2013; JAAD 47:950–953, 2002; cystic sebaceous carcinoma J Drugs Dermatol 6:540–543, 2007 Sebaceoma – multilobulated facial nodule AD 145:1325–1330, 2009 Seborrheic keratosis Spindle cell tumor Squamous cell carcinoma – multiloculated milia Cutis 89:45–47, 2012; squamous cell carcinoma associated with lichen planus – multilobulated, ulcerated, red nodule and plaque JAAD 71:698–707, 2014; genital squamous cell carcinoma – cerebriform (mulberrylike); multilobulated nodules BJD 171:779–785, 2014; cauliflowerlike tumor; complicating venous stasis ulcers South Med J 58:779–781, 1965 Stewart-Treves angiosarcoma – reddish-blue macules and/or nodules which become polypoid; pachydermatous changes, blue nodules, telangiectasias, palpable subcutaneous mass, ulcer; red-brown or ecchymotic patch, nodules, plaques in lymphedematous limb Cancer 1:64–81, 1948; JAAD 77:1009–1020, 2017; JAAD 67:1342–1348, 2012 Syringocystadenoma papilliferum – cerebriform multilobulated pink nodules of legs AD 148:1411–1416, 2012; giant multilobulated linear tumor Ped Derm 26:758–759, 2009; linear multilobulated verrucous plaque Ped Derm 28:61–62, 2011 Syringomatous carcinoma – multilobulated digital nodule BJD 144:438–439, 2001 Torus palatinus Tumoral melanosis – multilobulated nodule as marker of regressed melanoma BJD 175:391–393, 2016

SYNDROMES Benign symmetrical lipomatosis AD 126:235–240, 1990; JAAD 18:359–362, 1988 Birt-Hogg-Dube syndrome – trichoblastoma; multilobulated scalp nodule BJD 160:1350–1353, 2009 Blue rubber bleb nevus syndrome – personal observation Buschke-Ollendorff syndrome – connective tissue nevi and osteopoikilosis; single or multiple yellow, white, or skin colored papules, nodules, plaques of extremities; mountain range skin colored nodules; LEMD3 mutation BJD 166:900–903, 2012; Ped Derm 28:447–450, 2011; JAAD 48:600–601, 2003; Derm Wochenschr 86:257–262, 1928 Carney complex – cutaneous myxoma AD 141:916–918, 2005 Delleman-Oorthuys syndrome Clin Genet 25:470–472, 1984 Dercum’s disease (adiposis dolorosa) – painful peri-articular lipomas and ecchymoses; lipomas feel like “bag of worms” JAAD 44:132–136, 2001 Encephalocranial lipomatosis (nevus psiloliparus) – hairless with abundant fatty tissue JAAD 63:1–22, 2010 Familial multiple lipomatosis JAAD 15:275–279, 1986 Goeminne syndrome – X-linked; torticollis, keloids, cryptorchidism, renal dysplasia AD 137:1429–1434, 2001; Acta Genet Med (Roma) 17:439–467, 1968 Goltz’s syndrome – raspberry-like papillomas of lips, perineum, ears, fingers, toes, buccal mucosa, and esophagus Hennekam syndrome – autosomal recessive; intestinal lymphangiectasia, lymphedema of legs and genitalia, gigantic scrotum and penis,

722 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 multilobulated lymphatic ectasias, small mouth, narrow palate, gingival hypertrophy, tooth anomalies, thick lips, agenesis of ear, pre-auricular pits, wide flat nasal bridge, frontal upsweep, platybasia, hypertelorism, pterygium colli, hirsutism, bilateral single palmar crease, mild mental retardation, facial anomalies, growth retardation, pulmonary, cardiac, hypogammaglobulinemia Ped Derm 23:239–242, 2006 Infantile myofibromatosis Ped Derm 27:29–33, 2010 Juvenile hyaline fibromatosis – infiltration and multinodularity of nose; mutation of capillary morphogenesis protein 2 gene BJD 157:1037–1039, 2007 Multiple lipomas due to intracranial lesions (Frohlich syndrome) Lipomas, multiple Lipomatosis of Touraine and Renault Maffucci’s syndrome– multilobulated blue lesion; deformed hands; post-zygotic somatic mutations in isocitrate dehydrogenase (IDH1); enchondromas and spindle cell hemangioendotheliomas; cancers associated in Maffucci’s syndrome include lymphangiosarcoma, fibrosarcoma, angiosarcoma, osteosarcoma, mesenchymal ovarian tumors, gliomas, breast cancer, pancreatic cancer, and liver adenocarcinoma Ped Derm 36:947–948, 2019 Michelin tire baby syndrome – smooth muscle hamartomas JAAD 28:364–370, 1993; nevus lipomatosus superficialis AD 115:978– 979, 1979; AD 100:320–323, 1969 Muir-Torre syndrome – personal observation Multicentric reticulohistiocytosis – digital papule; knuckle pads; yellow papules and plaques JAAD 44:373–375, 2001; AD 126:251–252, 1990; Oral Surg Oral Med Oral Pathol 65:721– 725, 1988; Pathology 17:601–608, 1985; JAAD 11:713–723, 1984; AD 97:543–547, 1968

trixomas; facial papules; may be multilobulated JAMA Derm 149:559–564, 2013

TRAUMA Verrucous hyperplasia of the stump Verruciform xanthoma – red-orange plaque; multilobulated, vegetative, cobblestoned; perigenital; seen in KID, CHILD, syndromes and recessive dystrophic epidermolysis bullosa; usually at site of friction or frequent trauma Ped Derm 37:176–179, 2020

VASCULAR Agminated eruptive pyogenic granuloma-like lesions over congenital vascular stains (capillary malformations) Ped Derm 29:186–190, 2012 Angiokeratoma AD 143:318–325, 2007 Angiosarcoma Cutis 83:91–94, 2009; violaceous multilobulated tumor JAAD 65:448–449, 2011 Angiolymphoid hyperplasia with eosinophilia AD 136:837–839, 2000; JAAD 37:887–920, 1997; Cutis 60:281–282, 1997 Blue rubber bleb nevus syndrome – perianal vascular lesions Ped Derm 16:222–227, 1999; adult onset SKINMed 13:406–409, 2015; Case Rep Surg 2014; 683684 Elephantiasis nostras of penis AD 137:1095–1100, 2001 Glomus tumors – multiple or plaque type; hemi-facial JAAD 45:239– 245, 2001; Ped Derm 18:223–226, 2001; AD 127:1717–1722, 1991

Muscular dystrophy – pseudo-athletic appearance

Granulomatosis with polyangiitis Dermatol Clin 33:509–630, 2015

Neurofibromatosis type I – plexiform neurofibromas (“bag of worms”) JAAD 61:1–14, 2009

Hemangioma

Neurolipomatosis Alsberg

Klippel-Trenaunay-Weber syndrome – aneurysmal venous dilatation JAAD 18:1169–1172, 1988

Nodular lipomatosis of Krabbe and Bartels Noonan’s syndrome – webbed neck, short stature, malformed ears, nevi, keloids, transient lymphedema, ulerythema ophryogenes, keratosis follicularis spinulosa decalvans JAAD 46:161–183, 2002; J Med Genet 24:9–13, 1987 Phakomatosis pigmentokeratotica – multilobulated pink nodules representing connective tissue nevus Ped Derm 25:76–80, 2008 Proteus syndrome – multiple lipomas, connective tissue nevi of palms and soles; somatic mosaic mutation of AKT1 NEJM 365:611– 619, 2011;Ped Derm 11:222–226, 1994; multilobulated cerebriform scalp nodule (connective tissue nevus) JAAD 67:890–897, 2012 Pseudolipomatosis of Verneuil and Patain Rubinstein-Taybi syndrome – keloids; CREB-binding protein (transcriptional coactivator) AD 137:1429–1434, 2001 SOLAMEN syndrome (segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus) Eur J Hum Genet 15:767–773, 2007 Steatocystoma multiplex

Hemolymphangioma

Lipomyxangioma Lymphangiectasia (acquired lymphangioma) – due to scarring processes such as recurrent infections, radiotherapy, scrofuloderma, sclerederma, keloids, tumors, tuberculosis, repeated trauma BJD 132:1014–1016, 1996 Lymphangioma circumscriptum – frog spawn-like appearance BJD 83:519–527, 1970 Lymphatic malformation – multilobulated nodule with edematous vulva Cutis 93:297–300, 2014; superficial microcystic lymphatic malformation – pigmented, multinodular sessile tumor of leg Ped Derm 32:867–868, 2015 Lymphedema of vulva – chronic infection, recurrent streptococcal cellulitis Genital Skin Disorders, Fischer and Margesson, CV Mosby, 1998, p. 222–223 Lymphostasis verrucosa cutis PHACES syndrome – giant multilobulated hemangioma with hemihypertrophy of face

Tuberous sclerosis – fibrous cephalic plaque of scalp – multipapillated firm plaque JAMADerm 155:1071–1072, 2019; giant angiofibromas JAAD 67:1319–1326, 2012; adenoma sebaceum JAAD 20:918–920, 1989; non-symmetrical subcutaneous lipomatosis; Koenen’s tumors; folliculocystic and collagen hamartoma – comedo-­ like openings, multilobulated cysts, scalp cysts and nodules JAAD 66:617–621, 2012

Port wine stain with epithelial and mesenchymal hamartomas JAAD 50:608–612, 2004

Turner’s syndrome – keloids JAAD 74:231–244, 2016; JAAD 46:161–183, 2002; West J Med 137:32–44, 1982; multiple piloma-

Venous malformations BJD 162:350–356, 2010; AD 139:1409– 1416, 2003

Pyogenic granuloma Spindle cell hemangioma – multilobulated violeaceous nodule AD 142:641–646, 2006 Tufted angioma Advances in Dermatol 24:105–124, 2008

Nodules, Multiple, Subcutaneous

NODULES, MULTIPLE, SUBCUTANEOUS  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Dermatomyositis – calcinosis cutis AD 140:365–366, 2004; juvenile dermatomyositis with calcinosis cutis BJD 144:894–897, 2001; panniculitis Pan Afr Med J 33:149, 2016 Lupus erythematosus – nodular mucinosis of SLE Cutis 72:366– 371, 2003; BJD 137:450–453, 1997; J Rheumatol 21:940–941, 1994; JAAD 27:312–315, 1992; Int J Derm 31:649–652, 1992; panniculitis Cureus 12:e6790, 2020 Morphea profunda J Dermatol 46:354–357, 2019 Rheumatoid arthritis – rheumatoid nodules JAAD 46:161–183, 2002; rheumatoid nodulosis Arthritis Rheum 29:1278–1283, 1986; J Rheumatol 6:286–292, 1979; rheumatoid vasculitis BJD 147:905– 913, 2002 Still’s disease (juvenile rheumatoid nodule) Ann Rheum Dis 17:278–283, 1958

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36:82–84, 1995; Am J Roentgenol 159:1099–1100, 1992; JAMA 213:2271–2272, 1970; NEJM 255:433–434, 1956 Oleomas – multiple subcutaneous oleomas due to injection with sesame seed oil BJD 149:1289–1290, 2003; JAAD 42:292–294, 2000 Polyvinyl pyrrolidone injections Siliconomas – distant migration following breast implant rupture Plast Reconstr Surg Glob Open 4:e1011, 2016

INFECTIONS Acanthamoeba J Clin Inf Dis 20:1207–1216, 1995 Actinomycetoma (actinomycosis) (A. israelii) – primary cutaneous – subcutaneous nodules with draining sinuses NEJM 372:264, 2015; Hum Pathol 4:319–330, 1973 African histoplasmosis Alveolar echinococcosis JAAD 34:873–877, 1996 Bacillary angiomatosis BJD 126:535–541, 1992 Botryomycosis Indian Dermatol Online J 10:311–315, 2019 Candida sepsis JAAD 80:869–880, 2019

CONGENITAL LESIONS Congenital cartilaginous rests of the neck Cutis 58:293–294, 1996 Fibrous hamartoma of infancy – multiple subcutaneous nodules AD 144:547–552, 2008

Cat scratch disease AIDS 3:751–753, 1989 Chagas’ disease – painful subcutaneous nodules Transplant Proc 37:2793–2798, 2005 Chromomycosis Mycoses 31:343–352, 1988 Cryptococcosis – renal transplant recipient Cysticercosis Indian Dermatol Online J 10:574–576, 2019;

DRUG-INDUCED DRESS – lymphadenopathy Cutis 89:180–182, 2012 Exenatide AACE Clin Case Rep 5:e197–200, 2019 HAART – induction of multiple lipomas AD 143:1596–1597, 2007 Imatinib-induced Epstein-Barr virus and B-cell lymphoproliferative disease AD 143:1222–1223, 2007 Indinavir – multiple angiolipomas due to protease inhibitors JAAD 42:129–131, 2000; BJD 143:1113–1114, 2000

JAAD 50:S14–17, 2004; Int J Dermatol 34:574–579, 1995 Fusarium solani, disseminated JAAD 47:659–666, 2002; J Med Vet Mycol 24:105–111, 1986 Leishmania JAAD 36:847–849, 1997; Int J Dermatol 26:300–304, 1987; diffuse cutaneous leishmaniasis; L. martiniquensis – multiple subcutaneous fibrotic BJD 173:663–670, 2015 Leprosy – reactional state in tuberculoid leprosy JAMADerm 153:313–314, 2017; Indian J Lepr 65:239–242, 1993 Loiasis Clin Infect Dis 29:680–682, 1999

L-asparaginase – acute pancreatitis Ped Derm 26:47–49, 2009

Lymphogranuloma venereum – sign of the groove

Methotrexate-induced accelerated rheumatoid nodulosis Medicine 80:271–278, 2001; J Dermatol 26:46–464, 1999; JAAD 39:359–362, 1998

Mucormycosis J Cut Pathol 41:483–486, 2014

Minocycline-induced p-ANCA+ cutaneous polyarteritis nodosa – multiple subcutaneous nodules of the legs Eur J Dermatol 13:366– 368, 2003; JAAD 44:198–206, 2001 Zidovudine – multiple subcutaneous nodules due to insect bites JAAD 46:284–293, 2002

EXOGENOUS AGENTS Aluminum-containing allergen extracts Eur J Dermatol 11:138–140, 2001 Facial lipogranulomas – self-injection of Vitamin A oil – facial nodules Int J Womens Dermatol 5:126–128, 2018

Mycetoma Mycobacterium abscesses J Cut Med Surg 5:28–32, 2001 Mycobacterium avium complex – subcutaneous nodules Rev Inf Dis 11:625–628, 1989 Mycobacterium avium-intracellulare BJD 142:789–793, 2000; J Dermatol 25:384–390, 1998; BJD 130:785–790, 1994 Mycobacterium chelonae AD 123:1603–1604, 1987; kansasii, haemophilum BJD 131:379, 1994; scrofulaceum, marinum, fortuitum, abscessus, avium-intracellulare Clin Inf Dis 19:263–273, 1994 Mycobacterium tuberculosis – tuberculous cervical adenitis Ped Derm 37:29–39, 2020; renal transplant recipient Transplant Proc 51:1618– 1520, 2019; nodular tuberculid Ann Dermatol 29:95–99, 2017

Iatrogenic calcium deposits – calcium infusion for tetany Arch Pediatr 53:215–223, 1936; pitressin tannate Br J Radiol 57:921– 922, 1984

Nocardia – abscesses J Dermatol 26:829–833, 1999; lymphocutaneous nocardiosis Acta DV 74:447–448, 1994; actinomycetomas – multiple subcutaneous nodules; N. brasiliensis; Actinomadura madurae BJD 158:698–674, 2008

Iodide mumps – iodine contrast agent; giant acute inflammatory swelling of submandibular, sublingual, or parotid glands Ann Int Med 145:155–156, 2006; Circulation 104:2384, 2001; Acta Radiol

Onchocerciasis – onchocercomas AD 140:1161–1166, 2004; BJD 121:187–198, 1989

724 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Paragonimiasis westermani – subcutaneous migratory masses AXXCBFZZZ 31:200–203, 2019 Phaeohyphomycosis (Exophiala) – nodules of finger and multiple subcutaneous nodules of the foot JAAD 61:977–985, 2009 Pseudomonas aeruginosa Cutis 63:161–163, 1999 Rheumatic fever JAAD 8:724–728, 1983 Rhinosporidiosis Indian Heart J 45:463–467, 1993; Indian J Pathol Microbiol 40:95–98, 1997 Sporotrichosis – multiple disseminated subcutaneous nodules Rev Soc Bras Med Trop 50:871–873, 2017 Streptocerciasis – Mansonella streptocerca – similar rash to onchocerciasis; acute or lichenified papules with widespread lichenification and hypopigmented macules Syphilis – subcutaneous secondary syphilis J Dermatol 44:1401– 1403, 2017; scalp nodules Int J Dermatol 58:e203–204, 2019; Clin Dermatol 23:555–564, 2005 Toxocariasis – (T. canis, T. cati, T. leonensis) visceral larva migrans – migrating panniculitis JAAD 59:1031–1042, 2008; Dermatologica 144:129–143, 1972 Trichophyton rubrum – numerous lower extremity subcutaneous nodules BMC Inf Dis 19:271, 2019 Yaws – tertiary – gumma; multiple subcutaneous nodules; overlying skin ulcerates with purulent discharge; atrophic pigmented scars Zygomycosis – subcutaneous zygomycosis JAAD 30:904–908, 1994

INFLAMMATORY DISEASES Fat necrosis – nodular cystic fat necrosis JAAD 21:493–498, 1989; membranous fat necrosis AD 129:1331, 1334, 1993 Hidradenitis suppurativa Derm Surg 26:638–643, 2000; BJD 141:231–239, 1999 IgG4 disease J Dermatol 44:288–296, 2017; JAAD 75:197–202, 2016 Lymphadenopathy, reactive Proliferative fasciitis – multiple rapidly growing painful subcutaneous nodules in children following trauma; spontaneous resolution AD 144:255–260, 2008; JAAD 55:1036–1043, 2006; Cancer 36:1450–1458, 1975 Proliferative myositis Clin Exp Dermatol 22:101–103, 1997 Relapsing polychondritis – nodules of limbs Medicine 80:173–179, 2000 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) Int J Derm 37:271–274, 1998 Sarcoidosis (Darier-Roussy sarcoid) JAAD 72:924–926, 2015; JAAD 54:55–60, 2006; Clin Exp Dermatol 19:356–358, 1994; Ann Dermatol Syphil 5:144–149, 1904Subcutaneous fat necrosis of the newborn – red to bluish-red firm nodules and/or plaques; buttocks, thighs, shoulders, back, cheeks, and arms Clin Pediatr 20:748–750, 1981 Whipple’s disease – multiple subcutaneous nodules mimicking rheumatoid nodules; macular and reticulated erythema; Addisonian hyperpigmentation; Tropheryma whipplei JAAD 60:277–288, 2009

INFILTRATIVE LESIONS Amyloidosis – subcutaneous nodular amyloidosis Hum Pathol 32:346–348, 2001; beta-2 microglobulin amyloidosis – shoulder pain, carpal tunnel syndrome, flexor tendon deposits of hands, lichenoid papules, hyperpigmentation, subcutaneous nodules (amyloidomas) Int J Exp Clin Inves 4:187–211, 1997; South Med J 88:876–878, 1995; Arch Pathol Lab Med 118:651–653, 1994; J Clin Pathol 46:771–772, 1993; Nephron 55:312–315, 1990; Nephron 53:73–75, 1989; dialysis-related beta-2 microglobulin amyloidosis of buttocks BJD 149:400–404, 2003; bilateral popliteal tumors Am J Kidney dis 12:323–325, 1988; multiple primary cutaneous nodular amyloidosis Dermatol Online J May 15, 2017 Atypical cutaneous mucinosis SKINMed 16:428–431, 2018 Cutaneous mucinosis of infancy – skin colored rubbery nodules Ped Derm 27:299–300, 2010; AD 116:198–200, 1980 Hereditary progressive mucinous histiocytosis – infantile dermal nodules of scalp, trunk, and extremities Dermatology 36:958–960, 1997

METABOLIC DISEASES Albright’s osteodystrophy – with osteoma cutis; painful subcutaneous nodules and shortened digits Ped Derm 36: 944–945, 2019 Calciphylaxis Case Rep Nephrol Dial 9:119–125, 2019 Cerebrotendinous xanthomatosis – mutation of sterol 27-hydroxylas (mitochondrial enzyme); increased cholestanol BJD 142:378–380, 2000 Dermal hematopoiesis, neonatal Ped Derm 14:383–386, 1997; extramedullary hematopoiesis JAAD 58:703–706, 2008 Gout AD 134:499–504, 1998; Arthritis Care Res 9:74–77, 1996 Nephrogenic fibrosing dermopathy (nephrogenic systemic fibrosis) BJD 158:607–610, 2008; JAAD 48:42–47, 2003 Oxalate granulomas BJD 128:690–692, 1993 Pancreatic fat necrosis Am J Med Sci 319:68–72, 2000 Pretibial myxedema

Juvenile hyaline fibromatosis (infantile systemic hyalinosis) Ped Derm 23:458–464, 2006

Primary osteoma cutis – generalized osteomas; unilateral anodontia, hemihypertrophy, linear basal cell nevus

Langerhans cell histiocytosis Int Med Case Rep J 11:65–68, 2018; Clin Exp Dermatol 27:135–137, 2002

Pseudohypothyroidism type 1A – osteoma cutis World J Clin Cases 8:589–593, 2020

Mastocytosis – vulvar nodules J Ped Adolesc Gyn 31:156–157, 2018

Tendinous xanthomas/tuberous xanthomas

Self-healing juvenile cutaneous mucinosis – red nodules of face, scalp, hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; JAAD 44:273–281, 2001; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973; in adulthood Am J Dermatopathol 41:60–64, 2019 Juvenile xanthogranuloma, micronodular AD 148:531–536, 2012

Cerebrotendinous xanthomatosis – periarticular tendon xanthomas; mutation in sterol 27-hydroxylase; increased serum cholestanol and urinary bile alcohols; normal serum cholesterol JAAD 45:292–295, 2001   Phytosterolemia (beta sitosterolemia)   Familial hypercholesterolemia   Familial combined hyperlipidemia   Familial type III hyperlipoproteinemia Weber-Christian disease or recurrent nodular panniculitis Rev Clin Esp 196:405–406, 410, 1996(Sp)

Nodules, Multiple, Subcutaneous

NEOPLASTIC DISEASES

Neurilemmomatosis BJD 125:466–468, 1991

Angiolipoma – arms, legs, abdomen AD 126:666–667, 669, 1990; AD 82:924–931, 1960

Neuromas – multiple palisaded encapsulated neuromas JAAD 62:358–359, 2010

Carcinoid tumors Tumori 76:44–47, 1990 Cylindromas AD 145:1277–1284, 2009 Dermatofibroma – metastasizing cellular dermatofibroma Am J Surg Pathol 20:1361–1367, 1996 Dermatofibrosarcoma protuberans J Pak Med Assoc 69:113–115, 2019

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Pilomatrixomas – multiple pilomatrixomas associated with myotonic dystrophy (Curschmann-Batten-Steinert disease) Ped Derm 28:74–76, 2011; Gardner’s syndrome Ped Derm 12:331–335, 1995; Turner’s syndrome; Trisomy 9; Rubenstein-Taybi syndrome Ped Derm 11:21–25, 1994; Sotos syndrome, Kabuki syndrome Plantar fibromatosis Cutis 68:219–222, 2001

Elastofibromas JAAD 50:126–129, 2004

Post-transplantation lymphoproliferative disorder AD 140:1140– 1164, 2004

Folliculosebaceous cystic hamartomas AD 139:803–808, 2003

Progressive nodular fibrosis of the skin Ann DV 104:141–146, 1977

Granular cell tumors AD 140:353–358, 2004; AD 140:353–358, 2004; JAAD 47:S180–182, 2002; BJD 143:906–907, 2000; JAAD 36:327–330, 1997; AD 126:1051–1056, 1990

Pseudo-cutaneous T-cell lymphoma in HIV disease – deep nodules AD 131:1281–1288, 1995

Infantile myofibromatosis – single or multiple (hundreds); head, neck, trunk Ped Derm 18:305–307, 2001; JAAD 41:508, 1999; AD 134:625–630, 1998; Cancer 48:1807–1818, 1981

Spindle cell hemangioendothelioma – multiple subcutaneous nodules; palmar giant cobblestoning; hypertrophy of hand Cutis 79:125–128, 2007

Kaposi’s sarcoma – African endemic lymphadenopathic KS AD 144:1217–1222, 2008

Squamous cell carcinoma/keratoacanthoma – recurrent on legs of elderly women

Keratoacanthomas of Ferguson-Smith

Stewart-Treves tumor (angiosarcoma post-lymphedema) Int J Clin Exp Pathol 12:680–688, 2019

Leiomyomas Leiomyosarcomas J Exp Clin Cancer Res 17:405–407, 1998; Am J Pediatr Hematol Oncol 14:265–268, 1992 Leukemia – leukemia cutis (AML, AMML) AD 134:1477–1482, 1998; chronic lymphocytic leukemia – multiple lymph nodes; chronic myelogenous leukemia – neutrophilic panniculitis BMJ Case Rep Oct 8, 2019 Lipoblastomas, including congenital lipoblastomatosis BJD 143:694, 2000; Ped Derm 15:210–213, 1998 Familial lipomatosis Acta Chir Belg 110:98–100, 2010; JAAD 15:275–279, 1986; Acta DV 60:509–513, 1980; Br J Clin Pract 28:101–102, 1974; of shoulder girdle Ann Int Med 117:749–752, 1992; spindle cell lipomas JAAD 48:82–85, 2003; familial multiple lipomatosis Cutis 79:227–232, 2007 Lymphoma – Sezary syndrome – lymphadenopathy NEJM 369:559–569, 2013; intravascular B-cell lymphoma mimicking erythema nodosum J Cutan Pathol 27:413–418, 2000; subcutaneous panniculitis-like T-cell lymphoma JAAD 50:465–459, 2004; cytophagic histiocytic panniculitis and subcutaneous panniculitis-like T-cell lymphoma JAAD 50:S18–22, 2004; AD 136:889–896, 2000; gamma/delta T-cell lymphoma AD 136:1024–1032, 2000; CD8+ T-cell lymphoma JAAD 53:1093–1095, 2005; lymphadenopathy; primary cutaneous natural killer/T-cell nasal type BJD 160:205–207, 2009; intravascular B-cell lymphoma – red patch overlying multiple subcutaneous nodules JAAD 61:885–888, 2009;; Burkitt’s lymphoma – multiple subcutaneous mountain range nodules JAAD 64:1196–1197, 2011; cutaneous extranodal natural killer T-cell lymphoma – multiple violaceous or red nodules of extremities, subcutaneous nodules, cellulitis, abscess-like lesions JAAD 70:1002–1009, 2014; diffuse large cell B-cell lymphoma – multiple red subcutaneous nodules of neck BJD 173:134–145, 2015 Melanoma, metastatic SKINmed 10:373–383, 2012 Metastases – multiple primary sites; squamous cell carcinoma of the cervix Int J Gynecol Cancer 11:78–80, 2001; metastatic carcinoid AD 141:93–98, 2005; prostate AD 143:937–942, 2007; Dermatology Online J 11:24, 2005; lymphadenopathy; lung cancer Proc (Baylor Univ Med Ctr)33:67–68, 2019 Multiple calcifying aponeurotic fibroma Ter Arkh 90:91–95, 2018 Multiple myeloma Clin Nuc Med 44:746–747, 2019

Schwannomatosis BJD 148:804–809, 2003

Trichilemmal cyst nevus – multiple subcutaneous nodules with cystic lesions with and without comedones in Blaschko distribution, filiform hyperkeratoses JAAD 57:S72–77, 2007 Undifferentiated pleomorphic sarcoma J Cutan Pathol 44:477–479, 2017

PRIMARY CUTANEOUS DISEASES Adiposis dolorosa (Dercum’s disease) JAAD 56:901–916, 2007 Granuloma annulare, subcutaneous (“pseudorheumatoid nodule”) Acta DV Croat 25:292–294, 2017; Pediatr 100:965–967, 1997; of forehead Ped Derm 5:407–408, 2008 Kimura’s disease – multiple large subcutaneous or salivary gland masses; young Asian men JAAD 43:905–907, 2000; J Rheumatol 22:774–776, 1995 Multiple symmetric lipomatosis (benign symmetric lipomatosis) (Launois-Bensaude syndrome) Int J Obesity 26:253–261, 2002; Int J Dermatol 44:236–237, 2005; Medicine 63:56, 1984 Painful piezogenic pedal papules JAAD 36:780–781, 1997

SYNDROMES Adiposis dolorosa (Dercum’s disease) – multiple painful periarticular lipomas JAAD 56:901–916, 2007; JAAD 44:132–136, 2001 Autoimmune lymphoproliferative syndrome NEJM 351:1409–1418, 2004 Bannayan-Riley-Ruvalcaba-Zonana syndrome (PTEN phosphatase and tensin homolog hamartoma) (PTEN hamartoma-­tumor syndrome) – lipomas and vascular malformations, macrosomia at birth, hypotonia, lipoid storage myopathy, dolichocephaly, frontal bossing, megalencephaly (macrocephaly), subcutaneous and visceral lipomas, ocular hypertelorism, long philtrum, thin upper lip, broad mouth, relative micrognathia, lipomas, penile or vulvar lentigines, facial verruca-like or acanthosis nigricans-like papules, multiple acrochordons, angiokeratomas, transverse palmar crease, accessory nipple, syndactyly, brachydactyly, capillary (vascular) café au lait macules, malformations, arteriovenous malformations,

726 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 lymphangiokeratoma, goiter, hamartomatous intestinal polyposis JAAD 56:541–564, 2007; AD 142:625–632, 2006; JAAD 53:639– 643, 2005 Benign symmetrical lipomatosis (horse-collar neck) (Madelung’s deformity) (multiple symmetric lipomatosis) – autosomal dominant; male alcoholics; lipomas of head, neck, shoulder girdle, proximal extremities; neuropathy BJD 143:684–686, 2000; Skeletel Radiol 24:72–73, 1995; of the lower abdomen, thighs Int J Dermatol 32:594–597, 1993; of the soles JAAD 26:860–862, 1992

toes; development of tumors is cranial to caudal, dorsal to ventral and proximal to distal; ossification after infections or trauma; scalp nodules large, firm, and immobile; mutation in ACVR1 gene JAAD 64:97–101, 2011 Hypereosinophilic syndrome Case Rep Med Nov 18, 2019 Gardner’s syndrome – multiple epidermoid cysts, osteomas (especially of facial bones), lipomas, fibromas Am J Surg 143:405– 408, 1982; Clin Exp Dermatol 1:75–82, 1976; nuchal fibroma – multiple lesions associated with Gardner’s syndrome JAAD 66:959–965, 2012

Birt-Hogg-Dube syndrome – giant disfiguring lipomas JAAD 50:810–812, 2004

Goltz’s syndrome (focal dermal hypoplasia) – giant fat herniations Ped Derm 22:420–423, 2005

Buschke-Ollendorff syndrome JAMADerm 152:844–845, 2016

Hemihyperplasia-Multiple Lipomatosis syndrome – hemihyperplasia at birth, moderate overgrowth, extensive congenital vascular stain (superficial capillary malformation), compressible blue nodule, multiple subcutaneous nodules, hemihypertrophy, syndactyly, thickened but not cerebriform soles, dermatomyofibroma JAAD 56:541–564, 2007; Soc Ped Derm Annual Meeting, July 2005; Am J Med Genet 130A–111–122, 2004; Am J Med Genet 79:311–318, 1998

CLOVES syndrome – truncal lipomas, vascular malformations, and acral musculoskeletal anomalies (scoliosis, spinal high flow lesions, neural tube defects, tethered cord, spasticity), bony overgrowth and deformity, macrodactyly Ped Derm 28:215–216, 2011 Congenital generalized myofibromatosis – autosomal recessive or dominant Ped Derm 21:154–159, 2004; Pediatr Pathol Lab Med 15:571–587, 1995 Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease) – multiple congenital purple nodules Cowden’s syndrome (PTEN hamartoma-tumor syndrome) – sclerotic fibromas; megalencephaly (macrocephaly), dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), hamartomatous intestinal polyposis AD 142:625–632, 2006; J Cut Pathol 19:346–351, 1992; type 2 segmental Cowden’s disease – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi (including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of limbs, ballooning of toes, bowel polyps, glomerulosclerosis, macrocephaly BJD 156:1089–1090, 2007; Eur J Dermatol 17:133–136, 2007 Diffuse infiltrative lymphocytosis syndrome (DILS) – autoimmune syndrome with oligoclonal expansion of CD8+ T lymphocytes in response to HIV antigens; lymphocytic infiltration of salivary glands (parotid glands) and viscera Clin Lab Haem 27:278–282, 2005 Ekbom’s syndrome (myoclonic epilepsy and ragged muscle fibers) (mitochondrial syndrome) – cervical lipomas JAAD 39:819–823, 1998 Encephalocraniocutaneous lipomatosis – unilateral or bilateral skin-colored or yellow domed papules or nodules of scalp (hairless plaque), head, and neck; ipsilateral cranial and facial asymmetry, cranial and ocular abnormalities, spasticity, mental retardation Ped Derm 10:164–168, 1993; Arch Neurol 22:144–155, 1970 Familial histiocytic dermatoarthritis syndrome – uveitis, destructive arthritis; papulonodular eruption Am J Med 54:793–800, 1973 Familial multiple lipomatosis NEJM 371:1237, 2014; familial angiolipomatosis Arch Pathol Lab Med 123:946–948, 1999 Farber’s disease (lipogranulomatosis) – lysosomal acid ceramidase deficiency (N-acylsphingosine amidohydrolase) (chromosome 8p22–21.2); deformed or stiff joints with painful limb contractures and red periarticular subcutaneous nodules(proximal and distal interphalangeal joints, wrist, elbow, knees, ankles, metatarsals), and progressive hoarseness; rarely nodules seen in conjunctivae, nostrils, ears, mouth; heart, liver, spleen, lung; progressive psychomotor retardation Ped Derm 26:44–46, 2009; Eur J Ped 157:515–516, 1998; AD 130:1350– 1354, 1994 Fibrodysplasia ossificans progressiva – heterotopic bone formation within soft tissues; multiple neonatal scalp nodules associated with malformation of the great toes (hallux valgus); hypoplastic great

Infantile myofibromatosis (multicentric infantile myofibromatosis) – gingival and joints are spared compared with Winchester syndrome and juvenile hyaline fibromatosis and infantile systemic hyalinosis J Dermatol 28:379–382, 2001; AD 136:597–600, 2000; JAAD 41:508, 1999 Infantile systemic hyalinosis – large subcutaneous nodules AD 144:1351–1359, 2008 Juvenile hyaline fibromatosis – large subcutaneous nodules of scalp, trunk, and extremities Hum Mut 39:1752–1763, 2018; AD 144:1351–1359, 2008; Ped Derm 18:400–402, 2001; Pathol Int 48:230–236, 1998 Leri-Weill dyschondrosteosis – mesomelic short stature syndrome with Madelung’s deformity; SHOX haploinsufficiency like Turner’s syndrome JAAD 50:767–776, 2004 Maffucci’s syndrome (enchondromatosis) – enchondromas and multiple venous malformations; spindle cell hemangioendothelioma; oral and intra-abdominal venous and lymphatic anomalies; short stature, shortened long bones with pathologic fractures; enchondromas undergo sarcomatous change in 30–40%; breast, ovarian, pancreatic, parathyroid, pituitary tumors JAAD 56:541–564, 2007; Cutis 69:21–22, 2002; Ped Derm 17:270–276, 2000; Ped Derm 12:55–58, 1995; Dermatologic Clinics 13:73–78, 1995; JAAD 29:894–899, 1993 Multiple endocrine neoplasia syndrome (MEN I) – lipomas JAAD 56:877–880, 2007; AD 133:853–857, 1997; collagenomas JAAD 42:939–969, 2000 Mandibuloacral dysplasia – autosomal recessive; progeroid facies; facial asymmetry, micrognathia, small nose, prominent eyes, large open fontanelles; congenital brown pigmentation of ankles progresses to mottled pigmentation; hypoplastic clavicles; contractures of lower extremities; failure to thrive; progressive glomerulopathy; subcutaneous calcified nodules; mutation in ZMPSTE24 (lamin) JAMADerm 151:561–562, 2015 Mucopolysaccharidosis type IX – autosomal recessive; hyaluronidase 1 deficiency; soft tissue masses, short stature, coarse facies, hypertrichosis, synophrys; accumulation of hyaluronic acid Ped Derm 33:594–601, 2016 Neurofibromatosis type I NEJM 365:2020, 2011; Dermatol Clinics 13:105–111, 1995; Curr Prob Cancer 7:1–34, 1982; NEJM 305:1617–1627, 1981 Nevoid basal cell carcinoma syndrome – multiple epidermal inclusions cysts

Nodules, Red, Extremities Pachyonychia congenita – multiple epidermoid cysts of volar upper extremities; keratin 17 mutation BJD 159:730–732, 2008 Penchaszadeh syndrome (nasopalpebral lipoma-coloboma syndrome) – eyelid lipoma Am J Med Genet 11:397–410, 1982

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Glomus tumors – multiple or plaque type; hemi-facial Cutis 83:24–27, 2009; JAAD 45:239–245, 2001; Ped Derm 18:223–226, 2001; AD 127:1717–1722, 1991 Henoch-Schonlein purpura Leung, Robson, 2000

Polyneuropathy with nerve angiomatosis and multiple soft tissue tumors Am J Surg Pathol 19:1325–1332, 1995

Kaposiform hemangioendothelioma JAAD 38:799–802, 1998

Proteus syndrome – soft tissue and bony hypertrophy of hands and feet, hemihypertrophy, exostosis, cranial hyperostosis, visceral hamartomas, lipomas, vascular malformations, linear epidermal nevi, connective tissue nevus, gigantism, mosaic distribution of lesions; cerebriform thickening of palms and soles, capillary, venous, lymphatic and combined slow-flow malformations (like Klippel-Trenaunay syndrome); mosaic distribution, progressive course, sporadic occurrence; bilateral ovarian cystadenomas, parotid monomorphic adenoma, lipomas, lung cysts, facial phenotype JAAD 56:541–564, 2007; Eur J Pediatr 140:5–12, 1983;

Polyarteritis nodosa, systemic; cutaneous (livedo with nodules) – painful or asymptomatic red or skin colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk Ped Derm 15:103–107, 1998; AD 130:884–889, 1994; JAAD 31:561–566, 1994; JAAD 31:493–495, 1994

multiple lipomas JAAD 52:834–838, 2005; BJD 151:953–960, 2004; AD 140:947–953, 2004; JAMA 285:2240–2243, 2001; lipomatosis with hemihypertrophy Pseudohypoparathyroidism – dry, scaly, hyperkeratotic puffy skin; multiple subcutaneous osteomas, collagenoma BJD 143:1122– 1124, 2000 Pseudoxanthoma elasticum – multiple calcified cutaneous nodules Am J Med 31:488–489, 1961 SOLAMEN syndrome (segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus) Eur J Hum Genet 15:767–773, 2007 Steatocystoma multiplex SKINmed 12:267–269, 2014; JAAD 43:396–399, 2000; AD Syphilol 36:31–36, 1937 Sweet’s syndrome – secondary to melioidosis BMC Dermatol 19:16, 2019 Wells’ syndrome – eosinophilic panniculitis Eur J Dermatol 28:700–701, 2018 Winchester syndrome (hereditary contractures with sclerodermoid changes of skin) – scleredema-like skin changes, widespread nodules, joint contractures, gingival hyperplasia, hypertrichosis, dwarfism, arthritis of small joints (RA-like), osteolysis, corneal opacities JAAD 55:1036–143, 2006; JAAD 50:S53–56, 2004; Am J Med Genet 26:123–131, 1987; J Pediatr 84:701–709, 1974; Pediatrics 47:360–369, 1971

Klippel-Trenaunay-Weber syndrome

Takayasu’s arteritis NEJM 349:160–169, 2003 Giant varicosities, cirrhosis – personal observation

NODULES, RED, EXTREMITIES  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Deficiency of adenosine deaminase – ADA 1 – autosomal recessive; severe combined immunodeficiency; ADA 2 – loss of function mutation in cat eye syndrome chromosome candidate 1 gene (CECR1); painless leg nodules with intermittent livedo reticularis, Raynaud’s phenomenon, cutaneous ulcers, morbilliform rashes, Raynaud’s phenomenon, digital gangrene, oral aphthae; vasculitis of small and medium arteries with necrosis, fever, early recurrent ischemic and hemorrhagic strokes, peripheral and cranial neuropathy, and gastrointestinal involvement (diarrhea); hepatosplenomegaly, systemic vasculopathy, stenosis of abdominal arteries Ped Derm 37:199–201, 2020; NEJM 380:1582–1584, 2019; Ped Derm 33:602–614, 2016; NEJM 370:911–920, 2014; NEJM 370:921–931, 2014 Bowel arthritis dermatitis syndrome – erythema nodosum-like lesions Ped Derm 25:509–519, 2008; AD 135:1409–1414, 1999; Cutis 63:17–20, 1999; JAAD 14:792–796, 1986; Mayo Clin Proc 59:43–46, 1984; AD 115:837–839, 1979 Bullous pemphigoid without blisters – pemphigoid nodularis JAAD 81:355:363, 2019; JAMA Derm 149:950–953, 2013

TRAUMA

Chronic granulomatous disease JAAD 36:899–907, 1997; suppurative cutaneous granulomas in chronic granulomatous disease (Microascus cinereus) Clin Inf Dis 20:110–114, 1995; also Aspergillus, Candida, Paecilomyces, Exophiala dermatitidis, Acremonium strictum, Sarcinosporon inkin

Intravenous drug abuse – foreign body granulomas or nonspecific nongranulomatous inflammation; panniculitis BJD 150:1–10, 2004

Complement deficiency – low serum complement with SLE-like illness Clin Res 22:416(Abstract), 1974

VASCULAR DISEASES Angiolymphoid hyperplasia with eosinophilia J Clin Diagn Res 11:2D21–2D23, 2017 Arteriovenous malformation – mountain range appearance AD 143:1043–1045, 2007 Eosinophilic granulomatosis with polyangiitis JAAD 47:209–216, 2002; Mayo Clinic Proc 52:477–484, 1977 Congenital fibromuscular dysplasia – aneurysm in skin BJD 163:1362–1364, 2010; JAAD 27:883–885, 1992 Diffuse neonatal hemangiomatosis Ped Derm 14:383–386, 1997 Generalized lymphangiomatosis Ped Derm 15:296–298, 1998

Dermatitis herpetiformis – prurigo nodularis-like lesions J Eur Acad Dermatol Venereol 16:88–89, 2002 Dermatomyositis – calcinosis of elbows and forearms JAMA 305:183–190, 2011; panniculitis which may ulcerate and form sinuses Ped Derm 16:270–272, 1999; BJD 128:451–453, 1993; AD 119:336–344, 1983; nodular panniculitis AD 148:740–744, 2012; nodules and plaques on arms, thighs, buttocks, abdomen with lipoatrophy AD 127:1846–1847, 1991; JAAD 23:127–128, 1990; erythema nodosum Fogo selvagem (endemic pemphigus) – prurigo nodularis-like lesions JID 107:68–75, 1996; JAAD 32:949–956, 1995 Gain of function mutation of NLRC4 (inflammasome) – fever, periodic urticarial rash, conjunctivitis, arthralgias, painful red nodules of foot or leg, enterocolitis, splenomegaly, macrophage activation syndrome; increased IL-18 BJD 176:244–248, 2017; Nat

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Genet 46:1135–1139, 2014; Nat Genet 46:1140–1146, 2014; J Exp Med 211:2385–2396, 2014

fibrosis, thromboembolic events, erythema nodosum Leuk Lymphoma 44:547–548, 2003

GATA2 deficiency (includes MONOMAC syndrome, DCML, Emberger syndrome) (lymphedema and myelodysplasia) (familial acute leukemia and myelodysplasia) – monocytopenia, B-cell and natural killer cell lymphopenia, myeloid leukemias, disseminated mycobacterial infection, human papilloma virus infection, fungal infection; GATA2-transcription factor in early hematopoietic differentiation and lymphatic and vascular development; primary alveolar proteinosis; panniculitis; erythema nodosum-like lesions; primary lymphedema; skin tumors, Sweet’s syndrome with myelodysplastic syndrome BJD 178:593–594, 2018; JAAD 73:367–381, 2015; JAAD 71:577–580, 2014; BJD 170:1182–1186, 2014

Azathioprine – erythema nodosum-like nodules of legs in patients with inflammatory bowel disease AD 143:744–748, 2007; azathioprine hypersensitivity reaction – occurs within first four weeks of treatment; fever, malaise, arthralgias, myalgias, nausea, vomiting, diarrhea; morbilliform eruption, leukocytoclastic vasculitis, acute generalized exanthematous pustulosis, erythema nodosum, Sweet’s syndrome; red papulonodules with pustules JAAD 65:184–191, 2011

Hyper-IgD syndrome – recurrent transient and fixed pink plaques and nodules of face and extremities; cephalic pustulosis; mevalonate kinase deficiency Ped Derm 35:482–485, 2018 Lupus erythematosus – lupus panniculitis (lupus profundus) – thighs, buttocks, arms, breasts, face AD 122:576, 1986; AD 103:231–242, 1971; LE hypertrophicus et profundus – mimicking thrombophlebitis J Rheumatol 16:1400, 1989; chilblain lupus – chilblain-like lesions of legs Pemphigoid nodularis JAAD 53:S101–104, 2005; JAAD 29:293– 299, 1993; JAAD 21:1099–1104, 1989 Rheumatoid arthritis – neutrophilic lobular panniculitis JAAD 45:325–361, 2001; J R Soc Med 84:307–308, 1991; palisaded neutrophilic granulomatous dermatitis of rheumatoid arthritis (rheumatoid neutrophilic dermatosis) Cutis 78:133–136, 2006; JAAD 47:251–257, 2002; JAAD 45:596–600, 2001; AD 133:757– 760, 1997; AD 125:1105–1108, 1989 Sjogren’s syndrome – plasma cell panniculitis J Cutan Pathol 23:170–174, 1996; red nodules of legs JAAD 48:311–340, 2003

CONGENITAL LESIONS Dermoid cyst – red cystic nodule of back Ped Derm 30:706–711, 2013

Bortezomib (proteasome inhibitor for treatment of myeloma) – red nodules of trunk, face, neck, and extremities JAAD 71:217–227, 2014; JAAD 55:897–900, 2006 Calcium gluconate – calcinosis cutis; red nodules along veins Ped Derm 34:356–358, 2017 Corticosteroids – post-steroid panniculitis Ped Derm 5:92–93, 1988; AD 90:387–391, 1964; topical corticosteroid-­induced infantile gluteal granuloma Clin Exp Dermatol 6:23–29, 1981 Enfuvirtide – injection site reaction JAAD 49:826–831, 2003 Erythema nodosum – drug-induced erythema nodosum – sulfonamides, other antibiotics, analgesics, antipyretics, birth control pill, granulocyte colony-stimulating factor, all-trans retinoic acid Rook p. 3393, 1998, Sixth Edition 5-fluorouracil, capecitabine, tegafur – granulomatous septal panniculitis JAAD 71:203–214, 2014 FLT3 inhibitor in acute myelogenous leukemia – neutrophilic dermatosis JAMADerm 152:480–482, 2016 Furosemide – Sweet’s like JAAD 21:339–343, 1989 G-CSF – Sweet’s syndrome, pyoderma gangrenosum Ped Derm 17:205–207, 2000; neutrophilic dermatosis of legs and buttocks Ped Derm 18:417–421, 2001 Glatiramer acetate – injected for multiple sclerosis; panniculitis JAAD 55:968–974, 2006 Imatinib (Gleevec) BJD 149:678–678, 2003; imatinib-associated Sweet’s syndrome AD 141:368–370, 2005 Immunization granuloma

Leukemia cutis Dermatol Therapy 18:104–116, 2005; red-violaceous nodule; neonatal B-cell leukemia Ped Derm 36:988–989, 2019

Influenza vaccine – hypersensitivity to influenza vaccine in Epstein-Barr virus-associated T-lymphoproliferative disorder BJD 172:1686–1688, 2015

Sacrococcygeal teratoma – masquerading as infantile hemangioma; red vascular plaque; red subcutaneous nodule of medial buttock Ped Derm 30:112–116, 2013

Interleukin 2 injections – lobular panniculitis Br J Cancer 66:698– 699, 1992

Subcutaneous fat necrosis of newborn AD 146:882–885, 2010; Ped Derm 27:317–318, 2010   Neonatal subcutaneous nodules   Infection   Congenital leukemia   Dermoid cysts   Hemangiomas   Infantile myofibromatosis   Rhabdomyosarcoma   Infantile fibrosarcoma   Neuroblastoma   Sclerema neonatorum

Kit and BCR-ABL inhibitors – imatinib, nilotinib, dasatinib – facial edema morbilliform eruptions, pigmentary changes, lichenoid reactions, psoriasis, pityriasis rosea, pustular eruptions, DRESS, Stevens-Johnson syndrome, urticarial, neutrophilic dermatoses, photosensitivity, pseudolymphoma, porphyria cutanea tarda, small vessel vasculitis, panniculitis, perforating folliculitis, erythroderma JAAD 72:203–218, 2015

DRUG-INDUCED All-trans-retinoic acid – Sweet’s syndrome-like neutrophilic panniculitis; solitary red nodule JAAD 56:690—693, 2007; Allretinoic acid syndrome; fever, respiratory distress, weight gain, leg edema, pleural effusions, renal failure, pericardial effusions, hypotension, vasculitis, hypercalcemia, bone marrow necrosis and

Iododerma – scaly red papules and nodules; secondary to amiodarone JAMADerm 151:891–892, 2015; Australas J Dermatol 28:119–122, 1987

Leukocyte colony stimulating factors AD 130:77–81, 1994 Meperidine AD 110:747–750, 1974 Methotrexate-related lymphoproliferative disorder – linear perilymphatic nodules of leg; linear bands; ulcerated and non-ulcerated red nodules JAMADerm 154:490–492, 2018; JAAD 61:126–129, 2009 Pembrolizumab – granulomatous panniculitis JAMADerm 153:721– 722, 2017 Pentazocine AD 110:747–750, 1974 Sorafenib – erythema nodosum JAMADerm 154:369–370, 2018

Nodules, Red, Extremities Sulindac-induced pancreatitis JAAD 45:325–361, 2001 Vasculitis secondary to various drugs; propylthiouracil nodular vasculitis Cutis 49:253–255, 1992 Vemurafenib – panniculitis (erythema nodosum-like; violaceous leg nodules) with arthralgias Ped Derm 34:337–341, 2017; Ped Derm 32:153–154, 2015; BJD 167:987–994, 2012; AD 148:363–366, 2012

EXOGENOUS AGENTS Aluminum hypersensitivity – vaccination sites Aspartame (Nutra-Sweet) – lobular panniculitis JAAD 24:298–300, 1991 BCG granulomas AD 142:249–250, 2006

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Bacille-Calmette-Guerin (BCG) infection, disseminated – nodules of scalp, back, and legs Ped Derm 36:672–676, 2019 Bacillus species in subacute combined immunodeficiency JAAD 39:285–287, 1998 Bartonella bacilliformis – Oroya fever with verruga peruana – red papules in crops become nodular, hemangiomatous or pedunculated; face, neck, extremities, mucosal lesions Ann Rev Microbiol 35:325–338, 1981 Bed bug bites (Cimex lectularius) NEJM 359:1047, 2008 Borrelia burgdorferi – nodular panniculitis J Infect Dis 160:596–597, 1992; Lyme borreliosis – acrodermatitis chronica atrophicans – red to blue nodules or plaques; tissue-paper-like wrinkling; pigmented; poikilodermatous; hands, feet, elbows, knees BJD 121:263–269, 1989: Int J Derm 18:595–601, 1979

BRAF inhibitors (vemurafenib or dabrafenib) – panniculitis and arthralgia AD 148:357–361, 2012

Brucellosis – red papulonodules of legs (erythema nodosum-like lesions) JAAD 48:474–476, 2003; Cutis 63:25–27, 1999; AD 117:40–42, 1981

Bromoderma – multiple red nodules of forehead, upper back, arms, and legs BJD 158:427–429, 2008

Botryomycosis – prurigo nodularis-like lesions; Staphylococcus aureus Cutis 80:45–47, 2007

Contact dermatitis, irritant

Buruli ulcer (Mycobacteria ulcerans subspecies shinshuense) – ulcerated red nodule of arm JAMA Derm 150:64–67, 2014

Mercury ingestion JAAD 37:131–133, 1997; mercury granulomas due to injections – violaceous nodules and plaques Cutis 88:189– 193, 2011 Paraffinoma Plast Reconstr Surg 65:517–524, 1980 Povidone panniculitis AD 116:704–706, 1980 RAF inhibitors (MAPK pathway) – vemurafenib and dabrafenib – exanthema warts and other hyperkeratotic lesions, keratoacanthomas, squamous cell carcinoma, melanocytic nevi, keratosis pilaris, seborrheic dermatitis, hyperkeratotic hand-foot reactions, photosensitivity, panniculitis with arthralgias, alopecia JAAD 72:221–236, 2015 Sea urchin spine Cutis 98:303–305, 2016 Silicone granuloma AD 117:366–367, 1981 Zyderm test site

Campylobacter jejuni – in HIV disease Rev Med Interne 18:257– 258, 1998 Candida sepsis – papules and nodules with pale centers Am J Dermatopathol 8:501–504, 1986; JAMA 229:1466–1468, 1974; septic panniculitis in infancy Textbook of Neonatal Dermatology, p.425, 2001; Candida kefyr – unilateral red nodules of leg, bullae, pustules; arterial thrombus of left iliac artery Cutis 91:137–140, 2013 Cat scratch disease – erythema nodosum Pediatrics 81:559–561, 1988 Chagas’ disease (American trypanosomiasis; T. cruzi) – reactivation chagoma Dermatol Clinics 29:53–62, 2011; AD 139:104–105, 2003; acute infection (chagoma) Dermatol Therapy 17:513–516, 2004 Chromomycosis JAAD 8:1–16, 1983

INFECTIONS AND INFESTATIONS

Coccidioidomycosis – red nodule of arm JAAD 49:944–949, 2003; of legs AD 143:548–549, 2007

Abscess

Corynebacterium jeikeium

Acanthamebiasis – in AIDS JAAD 42:351–354, 2000; Arch Int Med 157:569–572, 1997; AD 131:1291–1296, 1995; Cutis 56:285–287, 1995; NEJM 331:85–87, 1994; Ped Inf Dis 11:404–407, 1992; tender red nodules of trunk and extremities with necrosis and eschars AD 147:857–862, 2011; associated with CPAP machine BJD 174: 625–628, 2016

Cryptococcosis – cryptococcal panniculitis J Drugs Dermatol 14:519–522, 2015; indurated edematous nodules Cutis 84:93–96, 2009; AD 144:1651–1656, 2008; erythema nodosum-like (cryptococcal panniculitis) Cutis 85:303–306, 2010; AD 112:1734–1740, 1976; Arch Int Med 136:670–677, 1976; BJD 74:43–49, 1962 Cysticercosis

Actinomycetoma – Nocardiopsis dassonvillei AD 121:1332–1334, 1985

Dematiaceous fungal infections in organ transplant recipients – all lesions on extremities   Alternaria   Bipolaris hawaiiensis   Exophiala jeanselmei, E. spinifera, E. pesciphera, E. castellani   Exserohilum rostratum   Fonsacaea pedrosoi   Phialophora parasitica

Actinomycosis – panniculitis J Cutan Pathol 16:183–193, 1989 African histoplasmosis (Histoplasma capsulatum var. duboisii) -exclusively in Central and West Africa and Madagascar Clin Inf Dis 48:441, 493–494, 2009 AIDS – neutrophilic eccrine hidradenitis in HIV infection J Dermatol 25:199–200, 1998; Int J Dermatol 35:651–652, 1996 Alternariosis – Alternaria chartarum BJD 142:1261–1262, 2000; A. alternate – pink crusted nodule of leg AD 143:1583–1588, 2007; A. tenuissima AD 143:1583–1588, 2007

Deep dermatophytosis – dermal and subcutaneous tissue invasion; CARD9 mutation NEJM 369:1704–1714, 2013

Amebiasis – red nodules of extremities JAAD 147:735–740, 2011

Dirofilaria tenuis (raccoon heartworm) – red nodule of leg JAAD 73:929–944, 2015; Cutis 80:125–128, 2007

Aspergillosis – primary cutaneous aspergillosis JAAD 38:797–798, 1998; A. fumigatus – red nodules of legs AD 143:535–540, 2007

Fascioliasis – Fasciola hepatica (fluke parasite) – eosinophilic panniculitis JAAD 42:900–902, 2000

Bacterial sepsis

Fusarium – red nodule with central pallor Sabouradis 17:219–223, 1979; dusky nodules with central necrosis AD 146:1037–1042, 2010; dark nodules of leg Clin Inf Dis 32:1237–1240, 2001; F.

Bartonellosis – verruga peruana; bacillary angiomatosis

730 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 falciforme – starts as red nodule with or without central necrosis BJD 157:407–409, 2007 Fusobacterium – septic panniculitis in infancy Glanders – nodules with lymphangitis JAAD 54:559–578, 2006 Gnathostomiasis – red migratory swellings JAAD 68:301–305, 2013; BJD 145:487–489, 2001; JAAD 33:825–8, 1995; eosinophilic migratory panniculitis (larva migrans profundus – Gnathostoma doloresi or G. spinigerum) JAAD 11:738–740, 1984 Gonococcemia Am J Med Sci 260:150–159, 1970 Helicobacter cinaedi – erythema nodosum-like eruption Ann Intern Med 121:90–93, 1994 Hepatitis B – erythema nodosum JAAD 9:602–603, 1983; hepatitis A – nodular panniculitis Cutis 32:543–547, 1983; polyarteritis nodosa Herpes simplex – chronic HSV infection in AIDS – red nodule resembling basal cell carcinoma JAAD 36:831–833, 1997 Histoplasmosis – personal observation; Diagnostic Challenges V 77–79, 1994; AD 121:914–916, 1985 Insect bite reactions – personal observation Klebsiella species – septic panniculitis in infancy Leishmaniasis – papulotuberous lesions JAAD 60:897–925, 2009; Clinics in Dermatology 14:425–431, 1996; post-kala azar dermal leishmaniasis Leprosy – lepromatous leprosy including erythema nodosum leprosum (vasculitis) AD 138:1607–1612, 2002; AD 111:1575– 1580, 1975; subcutaneous lepromas erythema nodosum leprosum – new painful dermal or subcutaneous nodules with fever, anorexia, malaise, arthralgias and myalgias, epididymitis, orchitis, periostitis, dactylitis, lymphadenitis, hepatosplenomegaly, glomerulonephritis, iridocyclitis, panniculitis, edema of dermis JAAD 71:795–803, 2014; AD 111:1575–1580, 1975; targetoid red nodules with central necrosis AD 144:821–822, 2008 Lobomycosis – Lacazio(Loboa)loboi – legs, arms, face JAAD 53:931–951, 2005; Mycoses 55:298–309, 2012 Loiasis Meningococcemia, chronic BJD 153:669–671, 2005; Rev Infect Dis 8:1–11, 1986; acute Am J Med Sci 260:150–159, 1970 Microascus cinereus in chronic granulomatous disease J Clin Inf Dis 20:110–114, 1995 Milker’s nodules Mucormycosis – Mucor racemosus; mimicking panniculitis JAAD 66:975–984, 2012 Mycetoma JAAD 53:931–951, 2005; JAAD 49:S170–173, 2003; JAAD 32:311–315, 1995; Cutis 49:107–110, 1992; Australas J Dermatol 31:33–36, 1990; JAAD 6:107–111, 1982; Sabouraudia 18:91–95, 1980; AD 99:215–225, 1969  Eumycetoma   Pseudallescheria boydii   Madurella mycetomatis   Madurella grisea   Exophiala jeanselmei   Pyrenochaeta romeroi   Leptosphaeria senegalensis   Curvularia lunata   Neotestudina rosatii   Aspergillus nidulans   Aspergillus flavus   Fusarium spp   Cylindrocarpon spp   Bacterial mycetoma – aerobic actinomycetes   Actinomadura madurae

   Actinomadura pelletieri    Streptomyces somaliensis    Nocardia brasiliensis    Nocardia caviae    Nocardia asteroides    Nocardia otitidiscaviarum Mycobacterium abscessus – personal observation Mycobacterium avium complex – panniculitis Cutis 89:175–179, 2012 Mycobacterium chelonae JAAD 60:177–179, 2009; JAAD 36:495– 496, 1997; Ped Derm 14:370, 1994; panniculitis AD 126:1064–1067, 1990; from pedicure whirlpool footbath AD 139:629–634, 2003 Mycobacterium fortuitum Dermatol Clin 33:509–630, 2015; AD 139:629–634, 2003; following pedicures JAAD 54:520–524, 2006; draining cystic nodule of leg J Drugs in Dermatol 10:914–916, 2011 Mycobacterium gordonae Mycobacterium haemophilum AD 138:229–230, 2002; Clin Inf Dis 33–330–337, 2001 Mycobacterium interjectum – leg nodules BJD 159:1382–1384, 2008 Mycobacterium kansasii Cutis 67:241–242, 2001; JAAD 36:497– 499, 1997 Mycobacterium malmoense Mycobacterium marinum – nodule or papule of hands, elbows, knees becomes crusted ulcer or abscess; or verrucous papule; sporotrichoid; rarely widespread lesions Clin Inf Dis 31:439–443, 2000; Br Med J 300:1069–1070, 1990; AD 122:698–703, 1986; J Hyg 94:135–149, 1985 Mycobacterium massiliense – red brown nodules of posterior calves mimicking erythema induratum BJD 173:235–238, 2015 Mycobacterium scrofulaceum Clin Inf Dis 20:549–556, 1995 Mycobacterium tuberculosis – erythema induratum of Bazin (nodular vasculitis) – tuberculid; nodules on backs of erythrocyanotic lower legs; ulcerate Clin Inf Dis 70:1254–1257, 2020; AD 147:949–952, 2011; BJD 157:1293–1294, 2007; JAAD 45:325–361, 2001; AD 133:457–462, 1997; JAAD 14:738–342, 1986; panniculitis J Cutan Pathol 20:177–179, 1993; Ped Derm 13:386–388, 1996; miliary TB; nodular tuberculid – red to blue-red nodules JAAD 53:S154–156, 2005; Ped Derm 17:183–188, 2000; Mycobacterium tuberculosis – nodular granulomatous phlebitis (phlebitic tuberculid) – nonulcerative subcutaneous nodules along anterior and medial leg veins Am J Clin Dermatol 3:319–328, 2002; Histopathology 30:129–134, 1997 Mycobacterium vaccae J Clin Inf Dis 23:173–175, 1996 Myiasis – furuncular myiasis; true flies, 2-winged flies, botflies (Dermatobia hominis (human botfly) (Cuterebra polita, C. latifrons) (rodent or rabbit botfly)), warble flies (Hypoderma bovis, H. lineatum), flesh flies (Wohlfahrtia vigil, W. opaca), tumbu fly (Cordylobia anthropophaga, C. rodhaini) Cutis 94:281–284, 2014; JAAD 58:907–926, 2008; JAAD 50:S26–30, 2004; carbuncular plaque – Cordylobia JAAD 58:907–926, 2008; migratory myiasis – Gasterophilus intestinalis, Hypoderma spp. JAAD 58:907–926, 2008 Nocardia – sporotrichoid painful nodules of extremities Cutis 89:75–77, 2012; J Cutan Pathol 16:183–193, 1989; wrist nodule in chronic granulomatous disease Clin Inf Dis 33:235–239, 2001; Nocardia eccrine hidradenitis JAAD 50:315–318, 2004; septic panniculitis in infancy; Nocardia beijingensis – ulcerated nodules of legs BJD 166:216–218, 2012 North American blastomycosis – disseminated NEJM 356:1456– 1462, 2007 Onchocerciasis – red nodules of legs JAAD 73:929–944, 2015 Osteomyelitis – palpable painful mass of thigh

Nodules, Red, Extremities Paecilomyces lilacinus – nodules on legs Clin Inf Dis 34:1415–1417, 2002; JAAD 39:401–409, 1998; JAAD 37:270–271, 1997; red nodules with necrotic centers Ann Int Med 125:799–806, 1996 Panniculitis – infectious; Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas spp., Klebsiella spp., Nocardia, atypical mycobacteria, tuberculosis, Candida, Fusarium, Histoplasma capsulatum, Cryptococcus neoformans, Actinomycosis, Sporothrix schenckii, Aspergillus fumigatus, chromoblastomycosis JAAD 45:325–361, 2001 Pediculosis – body lice; generalized prurigo nodularis JAAD 82:551–569, 2020 Penicillium marneffei Phaeohyphomycosis – Exophiala J Clin Inf Dis 19:339–341, 1994 Phlegmon – personal observation Pythium insidiosum (pythiosis) (alga) (aquatic oocyte) – necrotizing hemorrhagic plaque; ascending gangrene of legs; Thailand; painful subcutaneous nodules, eyelid swelling and periorbital cellulitis, facial swelling, ulcer of arm or leg, pustules evolving into ulcers BJD 175:394–397, 2016; J Infect Dis 159:274–280, 1989 Post-streptococcal suppurative panniculitis Protothecosis BJD 146:688–693, 2002; JAAD 32:758–764, 1995; AD 125:1249–1252, 1989; Am J Clin Pathol 61:10–19, 1974 Pseudomonas aeruginosa – nodular ecthyma gangrenosum; in HIV JAAD 32:279–80, 1995; nodular panniculitis JAMADerm 1 50:628–632, 2014; J Eur Acad Dermatol Venereol 4:166–169, 1995; septic panniculitis in infancy; Pseudomonas sepsis – red nodules with bullae atop several Ped Derm 28:204–205, 2011; Ped Derm 23:243–246, 2006; Clin Inf Dis 26:188–189, 1998; AD 116:446–447, 1980

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violaceum) BJD 101:177–183, 1979; T. rubrum – violaceous nodules of thighs and lower legs – personal observation; T. mentagrophytes – violaceous nodules (pseudomycetoma) BJD 155:628–629, 2006 Toxocariasis JAAD 33:8 JAAD 75:19–30, 2016; 25–828, 1995 Toxoplasma gondii AD 136:791–796, 2000 Trypanosomiasis – African trypanosomiasis AD 13:1178–1182, 1995; trypanosomal chancre – red tender 2–5 cm nodule with blister on surface of forearm or leg Trichophyton rubrum –Majocchi’s granuloma (nodular folliculitis); invasive Trichophyton rubrum – hemorrhagic purpuric leg nodules in transplant patient AD 149:475–480, 2013 Trypanosoma brucei rhodesiense (African trypanosomiasis) – ulcerated nodule of leg; transmitted by tsetse fly in Tanzania, Malawi, Zambia, Zimbabwe; causes sleeping sickness; 2–5 cm trypanosomal chancre at site of bite with regional lymphadenopathy; chancres rare in Gambian sleeping sickness NEJM 369:763, 2013 Tularemia – Francisella tularensis; skin, eye, respiratory, gastrointestinal portals of entry; ulceroglandular, oculoglandular, glandular types; toxemic stage heralds generalized morbilliform eruption, erythema multiforme-like rash, crops of red nodules on extremities Cutis 54:279–286, 1994; Medicine 54:252–269, 1985 Tunga penetrans Yaws – secondary JAAD 54:559–578, 2006; tertiary – nodules, tuberous lesions Zygomycosis – violaceous necrotic and crusted nodules; Rhizopus spp. AD 143:417–422, 2007

Psittacosis – erythema nodosum J Hyg 92:9–19, 1984

INFILTRATIVE DISEASES

Pyomyositis – palpable painful mass of thigh Salmonella enteritis – erythema nodosum – personal observation

Amyloidosis – red translucent nodules of legs JAAD 71:1035–1037, 2014

Scabies – in babies – red nodules of trunk and extremities JAMA 321:604–605, 2019; Ped Derm 4:690–694, 2017; pseudo-CTCL BJD 124:277–278, 1991

Angioplasmocellular hyperplasia – red nodule with red rim, ulcerated nodule, vascular nodule of face, scalp, neck, trunk, and leg JAAD 64:542–547, 2011

Serratia marcescens – sepsis JAAD 58:S55–56, 2008; neutrophilic eccrine hidradenitis BJD 142:784–788, 2000; AD 121:1106–1107, 1985

Cutaneous lymphoid hyperplasia JAAD 65:112–124, 2011

Sparganosis – application sparganosis; painful red nodules Sporotrichosis Cutis 54:279–286, 1994; Dermatologica 172:203– 213, 1986; fixed cutaneous Staphylococcal aureus – abscess, sepsis Hautarzt 16:453–455, 1965; panniculitis J Cutan Pathol 16:183–193, 1989; septic panniculitis in infancy; nodular lymphangitis Ped Derm 34:103–104, 2017 Staphylococcus epidermidis – septic panniculitis in infancy Streptococcal species – septic panniculitis in infancy Group A streptococcal panniculitis – multiple red nodules of extremities Ped Derm 31:256–258, 2014

Generalized eruptive histiocytoma Erdheim-Chester disease (non-Langerhans cell histiocytosis) – multiple pink exophytic nodules – skin, pulmonary, vocal cord; bone, retro-orbital tissues, central nervous system, pituitary gland, large vessels, kidneys, retroperitoneum, heart; CD68+, CD1a BJD 173:540–543, 2015; Virchows Arch Pathol Anat 173:561–602, 1930 Histiocytosis Indeterminate cell histiocytosis – red nodule; multiple red papulonodules JAAD 57:1031–1045, 2007 Intralymphatic histiocytosis – red patch overlying swollen knee; livedo reticularis, papules, nodules, urticaria, unilateral eyelid edema AD 146:1037–1042, 2010 Jessner’s lymphocytic infiltrate

Syphilis – nodular syphilis; deep red oval nodules JAAD 82:1–14, 2020; JAMADerm 152:83–84, 2016; JAAD 57:S57–58, 2007; Sex Transm Dis 14:52–53, 1987; Jarisch-Herxheimer reaction; syphilis in AIDS Clin Inf Dis 23:462–467, 1996; syphilitic panniculitis – purple subcutaneous nodules of lower legs AD 148:269–270, 2012; tertiary – nodular (tubercular) form – firm, coppery, red nodules; often on arms; may be cyanotic on legs; late congenital syphilis – nodular syphilids, gummata

Langerhans cell histiocytosis – Hashimoto-Pritzker disease; congenital single yellow-red nodule with central ulceration Ped Derm 26:121–126, 2009

Tinea corporis – Trichophyton rubrum – Majocchi’s granuloma (nodular folliculitis) invasive JAAD 21:167–179, 1989; AD 81:779– 785, 1960; AD 64:258–277, 1954; invasive tinea corporis (T.

Self-healing juvenile cutaneous mucinosis – red nodules of face, scalp, hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple

Progressive mucinous histiocytosis BJD 142:133–137, 2000 Progressive nodular histiocytomas – dermal dendrocytes; red nodules of face, trunk, and extremities BJD 143:628–631, 2000; JAAD 29:278–280, 1993; AD 114:1505–1508, 1978

732 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973 Xanthoma disseminatum – red nodules in flexures NEJM 338:1138– 1143, 1998

INFLAMMATORY DISEASES Atypical lymphocytic lobular panniculitis (T cell dyscrasia) – spontaneously resolves; red plaques and nodules of arms and legs with associated edema; identical presentation as subcutaneous panniculitis-like T-cell lymphoma with hemophagocytosis JAAD 61:875–881, 2009; J Cutan Pathol 31:300–306, 2004 Cytophagic histiocytic panniculitis (nodule) AD 121:910–913, 1985 Eosinophilic fasciitis Eosinophilic panniculitis Ped Derm 12:35–38, 1995; J Dermatol 20:185–187, 1993 Equestrian cold panniculitis Erythema induratum (Whitfield) – nodules with edematous ankles Erythema nodosum JAMA 316:91–92, 2016; On Cutaneous Diseases. London:Johnson 1798

ERYTHEMA NODOSUM-ASSOCIATED CAUSES Semin Cutan Med Surg 26:114–125, 2007; Sem Arth Rheum 4:1, 1974 Acne fulminans Clin Exp Dermatol 2:351–354, 1977 Acupuncture therapy Adenocarcinoma of the colon, stomach African trypanosomiasis Amebiasis Ankylosing spondylitis Antiphospholipid antibody syndrome Ascariasis Aspergillosis Atypical mycobacterial infections Azathioprine JAMA 316:91–92, 2016 Behcet’s syndrome Borrelia burgdorferi infections Boutonneuse fever Breast abscesses Brucellosis Campylobacter Q J Med 28:109–124, 1959; asymptomatic campylobacter coli infection JAAD 24:285, 1991 Carcinoid – primary cutaneous carcinoid Histopathology 36:566– 567, 2000 Carcinoma of the uterine cervix Cat scratch disease AD 100:148–154, 1969 Celiac disease Chancroid Chlamydia psittaci Proc R Soc Med 75:262–267, 1982 Chronic active hepatitis Crohn’s disease Coccidioidomycosis JAAD 55:929, 942, 2006 Corynebacterium diphtheriae infections

Cytomegalovirus infections Dermatophyte infections Diverticulosis (itis) of the colon Drugs  Acetaminophen   Actinomycin D   All-trans retinoic acid  Aminopyrine  Amiodarone  Ampicillin  Antimony  Arsphenamine  Azathioprine  Bromides  Busulfan  Carbamazepine  Carbenicillin  Carbimazole  Cefdinir  Chlordiazepoxide  Chlorotrianisene  Chlorpropamide  Ciprofloxacin  Clomiphene  Codeine  Cotrimoxazole  D-penicillamine  Dapsone  Diclofenac  Dicloxacillin  Diethylstilbestrol  Disopyramide   Echinacea herbal therapy  Enoxacin  Erythromycin  Estrogens  Fluoxetine  Furosemide  Glucagon   Gold salts AD 107:602–604, 1973   Granulocyte colony-stimulating factor   Hepatitis B vaccine  Hydralazine  Ibuprofen  Indomethacin  Interleukin-2  Iodides  Isotretinoin   Leukotriene modifying agents (zileuton and zafirlukast)  Levofloxacin  Meclofenamate  Medroxyprogesterone  Meprobamate  Mesalamine  Methicillin  Methimazole  Methyldopa  Mezlocillin  Minocycline  Naproxen  Nifedipine  Nitrofurantoin  Ofloxacin  Omeprazole   Oral contraceptives AD 98:634–635, 1968

Nodules, Red, Extremities  Oxacillin  Paroxetine  Penicillin  Phenylbutazone  Phenytoin  Piperacillin  Progestins  Propylthiouracil  Pyritinol  Sorafenib JAMADerm 154:369–370, 2018  Sparfloxacin  Streptomycin  Sulfamethoxazole  Sulfisoxazole  Sulfonamides  Sulfones  Sulfonylureas  Sulfasalazine  Thalidomide  Ticarcillin  Trimethoprim   Typhoid vaccination  Vaccines  Verapamil Escherichia coli Factitial dermatitis Giardiasis Gonococcal disease Granulomatous mastitis Hepatitis B JAAD 9:602, 1983 Hepatitis C AD 131:1185–1193, 1995 Hepatocellular carcinoma Herpes simplex Hidradenitis suppurativa – personal observation Histoplasmosis Am Rev Resp Dis 117:929–956, 1978 HIV infection Hookworm infestation Hyalohyphomycosis – Paecilomyces lilacinus BJD 143:873–875, 2000 Hydatidosis Idiopathic Idiopathic granulomatous mastitis Ann DV 146:571, 2019; with erythema nodosum J Eur Acad DV 31:e391–393, 2017; arthritis Rheumatol Int 31:1093–1095, 2011

Lymphoma – Hodgkin’s disease BJD 106:593–595, 1982; nonHodgkin’s lymphoma Measles Meningococcal disease Milkers’ nodules Acta DV (Stockh) 56:69–72, 1976 Moraxella catarrhalis Mycobacterium szulgai in MonoMAC syndrome Clin Inf Dis 57:6978–699, 2013 Mycoplasma pneumoniae infections Myiasis, furuncular Med Cutan Ibero Lat Am 13:411–418, 1985 North American blastomycosis Am J Med 27:750–766, 1959 Pancreatic carcinoma Parvovirus B19 Pasteurella pseudotuberculosis infections Pertussis Post-radiation therapy for pelvic carcinoma Pregnancy Propionibacterium acnes Pseudomonas aeruginosa sepsis Am J Med 80:528–529, 1986 Psittacosis (Bateman’s syndrome) Br Med J ii:1469–1470, 1965 Q fever Radiation BJD 142:188, 2000; BJD 140:372–373, 1999 Relapsing polychondritis Reiter’s syndrome Renal carcinoma Rheumatoid arthritis Salmonella Br Med J 102:339–340, 1980 Sarcoidosis – Lofgren’s syndrome – erythema nodosum with sarcoidosis and arthralgias Ped Derm 22:366–368, 2005 Schistosomiasis Sarcoma Shigella infections Sjogren’s syndrome Smoke inhalation South American blastomycosis Sparganum larva Staphylococcus aureus – abscess (furuncle) Still’s disease, adult

IgA nephropathy

Streptococcal infection – pharyngitis and tonsillitis, erysipelas, rheumatic fever

Infectious mononucleosis Br Med J ii:1263, 1979

Sweet’s syndrome

Intestinal bypass for obesity

Syphilis

Intestinal parasitosis

Takayasu’s arteritis

Jellyfish sting

Thromboangiitis obliterans (Buerger’s disease) Am J Med Sci 136:567–580, 1908

Kerion Ped Derm 29:479–482, 2012 Klebsiella pneumoniae infections Leishmaniasis Leprosy Leptospirosis Br Med J 285:937–940, 1982 Leukemia AD 110:415–418, 1974 Lupus erythematosus, including C4 deficiency SLE Lymphogranuloma venereum Acta DV (Stockh) 60:319–322, 1980

Toxoplasmosis Trichomoniasis Trichophyton infections Pediatrics 59:912–915, 1977 Tropical eosinophilia Tuberculosis Tularemia JAAD 49:363–392, 2003 Ulcerative colitis Gut 5:1–22, 1964 Varicella

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734 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Vogt-Koyanagi disease Wegener’s granulomatosis Yersinia enterocolitica BJD 93:719–720, 1975; asymptomatic dog vector Erythema nodosum in children   Streptococcal infections most common cause Erythema nodosum in adults  Infections, drugs, sarcoidosis, autoimmune disorders, inflammatory bowel disease most common Febrile idiopathic lobar panniculitis of childhood – abdominal pain, arthralgia, fever, red nodules of face, legs, trunk, lipoatrophy Ped Derm 31:652, 2014 Granulomatous nodules – after mastectomy for breast carcinoma BJD 146:891–894, 2002 Histiocytic phagocytic panniculitis – red nodules of the forearms JAAD 44:120–123, 2001 Interstitial granulomatous dermatitis – personal observation IgG4 disease – multisystem inflammatory disease with papules, plaques, and nodules; parotitis with parotid gland swelling, lacrimal gland swelling, dacryoadenitis, sialadenitis, proptosis; idiopathic pancreatitis, retroperitoneal fibrosis, aortitis; Mikuliczs syndrome, angiolymphadenopathy with eosinophilia, Riedel’s thyroiditis, biliary tract disease, renal disease, meningeal disease, pituitary gland; Kuttner tumor, Rosai-Dorfman disease; elevated IgG4 with plasma cell dyscrasia, diffuse or localized swelling or masses; lymphocytic and plasma cell infiltrates with storiform fibrosis JAAD 75:177–185, 2016 Intralymphatic histiocytosis – red nodules associated with livedo reticularis J Drugs in Dermatol 10:1208–1209, 2011; Am J Dermatopathol 31:140–151, 2009; Am J Dermatopathol 29:165– 168, 2007 Kaposi’s sarcoma – HIV Lipoatrophic panniculitis Lipophagic panniculitis of childhood Malacoplakia JAAD 34:325–332, 1996 Membranous fat necrosis AD 129:1331, 1334, 1993 Membranous lipodystrophy Myositis – systemic or focal myositis – palpable painful mass of thigh Neutrophilic eccrine hidradenitis Ped Derm 6:33–38, 1989; AD 118:263–266, 1982 Neutrophilic panniculitis – not a diagnosis but a histologic pattern   Alpha-1 anti-trypsin deficiency   Familial Mediterranean fever   Infectious panniculitis   Pancreatic panniculitis   Panniculitic bacterid   Subcutaneous Sweet’s syndrome   Ulcerative colitis Palmoplantar hidradenitis in children AD 131:817–820, 1995 Panniculitis   1) Enzyme panniculitis    Alpha-1 antitrypsin deficiency JAAD 18:684–692, 1988    Pancreatic panniculitis – acute alcoholic pancreatitis NEJM 368:465, 2013   2) Immunologic panniculitis    Complement deficiency     Cytophagic histiocytic panniculitis    Erythema nodosum, including familial erythema nodosum Arthr Rheum 34:1177–1179, 1991     Lipoatrophic panniculitis

    Lipophagic panniculitis of childhood JAAD 21:971–978, 1989     Lupus panniculitis   3) Neoplastic     Lymphoma, leukemia    Histiocytosis  4) Cold panniculitis, including cold panniculitis of neonate – red nodules of cheeks; equestrian cold panniculitis   5) Factitial panniculitis   6) Post-steroid panniculitis   7) Crystal panniculitis   8) Eosinophilic panniculitis  9) Idiopathic nodular panniculitis (Weber-Christian disease) Medicine 64:181–191, 1985; relapsing idiopathic nodular panniculitis BJD 152:582–583, 2005  10) Associations with Sweet’s syndrome, sarcoid, Behcet’s disease, familial Mediterranean fever, Whipple’s disease, relapsing polychondritis  11) Lipomembranous panniculitis with nodular fat necrosis  12) Subcutaneous fat necrosis after hypothermic cardiac surgery JAAD 15:331–336, 1986   13) Subcutaneous fat necrosis of newborn  14) Sweet’s syndrome panniculitis JAAD 56:S61–62, 2007; Am J Dermatopathol 11:99–111, 1989   15) Neutrophilic panniculitis of infancy JAAD 57:S65–68, 2007  15a) Neutrophilic panniculitis – associated with:    Familial Mediterranean fever    Infections  – Staphylococcus, Streptococcus, Klebsiella, Nocardia, Candida, Fusarium, Histoplasmosis, Cryptococcus, Actinomyces   Panniculitic bacterid – associated with intranasal aspergilloma, streptococcal tonsillitis, viral pharyngitis, dental abscess, impetiginized dermatitis, breast abscess, staphylococcal cellulitis   Pseudomonas pneumonia   Ulcerative colitis  16) Granulomatous panniculitis in Sjogren’s syndrome – red nodules and plaques AD 144:815–816, 2008  17) Lipoatrophic panniculitis (lipophagic panniculitis of childhood; annular atrophy of the ankles, annular atrophic panniculitis of the ankles) – red nodules and red plaques of extremities; annular atrophy of ankle and/or dorsal foot Ped Derm 28:146–148, 2011; AD 146:877–881, 2010  18) Annular atrophic connective tissue panniculitis – erythematous nodules and plaques of ankles followed by circumferential band of atrophy Ped Derm 28:146–148, 2011; Ped Derm 28:142–145, 2011; J Cut Pathol 38:270–274, 2011; AD 146:877–881, 2010 Lymphocytoma cutis (pseudolymphoma) JAAD 38:877–905, 1998; Acta DV 62:119–124, 1982   Allergen injections  Carbamazepine   Cowpox vaccination   Gold hypersensitivity  Idiopathic   Insect bites   Lyme borreliosis  Phenytoin  Tattoos  Trauma Pyoderma gangrenosum Br J Plast Surg 53:441–443, 2000; JAAD 18:559–568, 1988 Relapsing polychondritis – erythema nodosum-like lesions; superficial thrombophlebitis Medicine 80:173–179, 2000 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – xanthoma-like lesions with grouped yellow-red papules

Nodules, Red, Extremities and nodules of head, neck, ears, trunk, arms and legs; cervical lymphadenopathy; also axillary, inguinal, and mediastinal adenopathy; hypergammaglobulinemia; emperipolesis (histiocytes with intracellular inflammatory cells and debris) JAAD 65:1069–1071, 2011; Int J Derm 37:271–174, 1998; Am J Dermatopathol 17:384– 388, 1995; Semin Diagn Pathol 7:19–73, 1990; Cancer 30:1174– 1188, 1972; red nodules JAMADerm 150:177–181, 2014; disseminated red papules and nodules of extremities JAMA 310:199–200, 2013 Sarcoid (Darier-Roussy sarcoid) JAAD 72:924–926, 2015; JAAD 54:55–60, 2006; Ann Dermatol Syphil 5:144–149, 1904; syringotropic sarcoid – localized hypohidrosis JAAD 68:1016–1021, 2013 Subacute nodular migratory panniculitis of Villanova and PinolAguade (erythema nodosum migrans) Acta DV (Stockh) 53:313– 317, 1973; AD 89:170–179, 1964 Subcutaneous fat necrosis of the newborn J Cutan Pathol 5:193– 199, 1978; AD 134:425–426, 1998 Sweet’s syndrome – edematous red nodules, hemorrhagic bullae, subcutaneous red nodule JAAD 79:987–1006, 2018 Ulcerative colitis with nodular panniculitis J Gastroenterol 29:84–87, 1994 Whipple’s disease – red nodules indicating immune reconstitution; macular and reticulated erythema; Addisonian hyperpigmentation; Tropheryma whipplei JAAD 60:277–288, 2009

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375:1972–1981, 2016; JAMADerm 151:95–96, 2015; NEJM 368:465, 2013; JAAD 45:325–361, 2001; JAAD 34:362–364, 1996; Arthritis Rheum 22:547–553, 1979; Am J Med 58:417–423, 1975; HIV infection and hemophagocytic syndrome BJD 134:804–807, 1996 Pretibial myxedema – personal observation Vascular calcification – cutaneous necrosis syndrome JAAD 33:53–8, 1995 Whipple’s disease – subcutaneous Whipple’s disease; leg nodules or erythema nodosum Xanthoma

NEOPLASTIC DISEASES Acrospiroma Cutis 58:349–351, 1996 Aneurysmal fibrous histiocytoma – red nodule of wrist Ped Derm 23:591–592, 2006; Cancer 47:2053–2061, 1981 Angioimmunoblastic T-cell lymphoma Angiosarcoma – Stewart-Treves tumor; hemorrhagic ulcerated plaque and nodule in chronic lymphedema JAAD 77:995–1006, 2017; AD 146:337–342, 2010 Atypical Spitzoid melanocytic tumors – bright pink nodule JAAD 64:919–935, 2011 Basal cell carcinoma – metastatic JAAD 59:S1–3, 2008

METABOLIC DISEASES Acquired depletion of C1-esterase inhibitor – lobular panniculitis Am J Med 8:959–962, 1987 Alpha-1 antitrypsin deficiency-associated panniculitis – red nodules of legs NEJM 382:1443–1455, 2020; JAAD 65:227–229, 2011; JAAD 51:645–655, 2004; Cutis 71:205–209, 2003; AD 123:1655– 1661, 1987 Blueberry muffin baby in hereditary spherocytosis – red nodules, generalized Cutis 101:111–114, 2018 Calcinosis cutis (dystrophic calcification) Cutis 60:259–262, 1997 Calciphylaxis Cutis 51:245–247, 1993; JAAD 22:743–747, 1990 Crohn’s disease – metastatic Crohn’s disease – red nodules of lower legs JAAD 10:33–38, 1984; granulomatous ulcer JAAD 41:476–479, 1999 Crystal panniculitis Cystic fibrosis-associated episodic arthritis – pink macules, urticarial papules, arthritis, purpura of legs, erythema nodosum, cutaneous vasculitis JAMADerm 155:375–376, 2019; Respir Med 88:567–570, 1994; Am J Dis Child 143:1030–1032, 1989; Ann Rheum Dis 47:218–223, 1988; Arch Dis Child 59:377–379, 1984 Diabetic muscle infarction – palpable painful mass of thigh Am J Med 101:245–250, 1996 Gout – gouty panniculitis with urate crystal deposition Cutis 76:54–56, 2005; Am J Dermatopathol 9:334–338, 1987; AD 113:655–656, 1977

Blastic plasmacytoid dendritic cell neoplasm – violaceous nodule Ped Derm 30:142, 144, 2013; violaceous nodule with golden contusiform rim JAMA Derm 150:73–76, 2014 Cartilaginous matrix-producing apocrine carcinoma – pink papulonodule BJD 163:215–218, 2010 CD 30+ lymphoproliferative disorders – red tumors, red plaques with or without necrosis, giant tumor JAAD 72:508–515, 2015 Cellular dermatofibroma – purple nodule of arm Ped Derm 35:403–405, 2018 Chondroid syringoma Clear cell acanthoma – personal observation Clear cell hidradenoma – brown-red nodule JAAD 54:S248–249, 2006; Ped Derm 22:450–452, 2005 Combined squamous cell carcinoma and Merkel cell carcinoma – crusted papule, red facial nodule, red papule, red nodule of wrist JAAD 73:968–975, 2015 Crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma – panniculitis Hum Pathol 27:84–87, 1996 Cytophagic histiocytic panniculitis – manifestation of hemophagocytic syndrome; red tender nodules; T-cell lymphoma, B-cell lymphoma, histiocytic lymphoma, sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) JAAD 4:181–194, 1981; Arch Int Med 140:1460–1463, 1980 Dermal duct tumor – red nodule of head, neck, arms, legs, or back AD 140:609–614, 2004

Intrahepatic cholestasis of pregnancy – prurigo nodularis-like lesions AD 143:757–762, 2007

Dermatofibrosarcoma protuberans – early, red papule/nodule Ped Derm 36:400–401, 2019; JAAD 57:548–550, 2007; JAAD 35:355– 374, 1996; nodules of leg Ped Derm 31:676–682, 2014

Nodular obesity-associated lymphedematous mucinosis – red nodules of legs JAMA Derm 149:867–868, 2013

Dermatomyofibroma – red nodule or plaque Ped Derm 16:154–156, 1999; pink nodule of shoulder AD 148:113–118, 2012

Pancreatic panniculitis – periarticular subcutaneous nodules of lower legs; post-traumatic pancreatitis, acute and chronic pancreatitis, pancreatic carcinoma, pancreatic pseudocyst, anatomical ductal anomaly of pancreas, pancreas divisum, vasculopancreatic fistulae JAMADerm 154:471–472, 2018; NEJM

Eccrine angiomatous hamartoma Ped Derm 14:401–402, 1997 Eccrine porocarcinoma JAAD 49:S252–254, 2003 Eccrine poroma and eccrine porocarcinoma – red nodule of ankle BJD 150:1232–1233, 2004

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Eccrine spiradenocarcinoma – red nodule of arm; tender, solitary subcutaneous nodule Cutis 92:285–287, 2013; Pol Med J 11:388– 396, 1972 Eccrine syringofibroadenoma BJD 142:1050–1051, 2000 Epithelioid sarcoma – personal observation Eruptive infundibulomas Ann DV 114:551–6, 1987 Extramedullary hematopoiesis in chronic idiopathic myelofibrosis with myelodysplasia JAAD 55:S28–31, 2006 Fibrosarcoma/spindle cell sarcoma – red or violaceous nodule Fibrous tumors of infants   Calcifying aponeurotic fibroma   Digital fibromatosis   Fibromatosis colli   Fibrous hamartoma of infancy   Hyaline fibromatosis   Infantile myofibromatosis AD 134:625–630, 1998   Intravascular fasciitis Fibrous histiocytoma Granular cell schwannoma – including prurigo nodularis-like lesions Int J Derm 20:126–129, 1981 Granulocytic sarcoma – violaceous nodule with green halo Cutis 94:65, 81–82, 2014 Hidradenocarcinoma, metastatic AD 142:1366–1367, 2006 Histiocytic lymphoma (true histiocytic lymphoma) JAAD 50:S9–10, 2004 Infantile myofibromatosis – purple nodules of legs Ped Derm 19:520–522, 2002; Curr Prob Derm 14:41–70, 2002 Kaposi’s sarcoma Dermatol Clin 24:509–520, 2006; AD 141:1311– 1316, 2005 Keratoacanthoma Leiomyoma – pink, red, dusky brown papules or nodules Cancer 54:126–130, 1984 Leiomyosarcoma JAAD 48:S51–53, 2003; JAAD 38:137–142, 1998; J Exp Clin Cancer Res 17:405–407, 1998; JAAD 21:1156–1160, 1989 Leukemia – acute lymphoblastic – purple nodules JAAD 38:620– 621, 1998; leukemia cutis – AML violaceous nodules Ped Derm 36:658–663, 2019; AD 110:415–418, 1974; monocytic leukemia – red, brown, violaceous nodule Cutis 85:31–36, 2010; AD 123:225– 231, 1971; eosinophilic leukemia AD 140:584–588, 2004; congenital leukemia cutis (AML) Ped Derm 25:34–37, 2008; natural killer cell CD 56- large granular lymphocytic leukemia – panniculitis JAAD 62:496–501, 2010; aleukemic leukemic cutis – purple nodule of thigh JAAD 63:539–541, 2010 Lipoblastoma Lymphadenoma, cutaneous – pink nodule of face or leg AD 144:255–260, 2008; J EurAcad Dermatol Venereol 15:481–483, 2001; Am J Dermatopathol 18:186–191, 1996; Am J Surg Pathol 15:101–110, 1991 Lymphangiosarcoma (Stewart-Treves tumor) – red-brown or ecchymotic patch, nodules, plaques in lymphedematous limb Arch Surg 94:223–230, 1967; Cancer 1:64–81, 1948 Lymphoma/leukemia – subcutaneous panniculitic T-cell lymphoma; JAAD 79:892–898, 2018; The Dermatologist, October 2014, pp.42–44; JAAD 50:S18–22, 2004; BJD 148:516–525, 2003; AD 138:740–742, 2002; JAAD 36:285–289, 1997; AD 132:1345–1350, 1996; AD 129:1171–1176, 1993; subcutaneous panniculitis-­like T-cell lymphoma alpha/beta Ped Derm 32:526–532, 2015; BJD 163:1136–1138, 2010; subcutaneous panniculitis-like T-cell lymphoma (with hemophagocytic syndrome) – blue-red nodules of

extremities and face with edema of legs JAAD 61:875–881, 2009; Ped Derm 23:537–540, 2006; Am J Surg Pathol 15:17–27, 1991;; EBV-associated natural killer/T-cell lymphoproliferative disorder – painful red subcutaneous nodules of legs AD 147:216–220, 2011; primary cutaneous follicle center lymphoma with diffuse CD 30 expression – papules, plaques, nodules, multilobulated scalp tumor JAAD 71:548–554, 2014; folliculocentric cutaneous T-cell lymphoma – prurigo lesions JAAD 70:205–220, 2014; gamma/delta T-cell lymphoma JAAD 56:643–647, 2007; JAAD 34:904–910, 1996; lymphomatoid granulomatosis – angiocentric T-cell lymphoma AD 127:1693–1698, 1991; AD 132:1464–1470, 1996; CD30- CTCL AD 1331:1009–1015, 1995; primary cutaneous anaplastic large cell lymphoma CD 30+ −– red nodule of the arm JAAD 70:374–376, 2014; AD 145:1399–1404, 2009; AD 145:667–674, 2009; BJD 157:1060–1061, 2007; post-transplant lymphoma JAAD 81:600–602, 2019; B cell lymphoma overlying acrodermatitis chronica atrophicans associated with Borrelia burgdorferi infection JAAD 24:584–590, 1991; nasal NK/T-cell lymphoma JAAD 46:451–456, 2002; NK/T-cell lymphoma – ulcerated red nodule of leg BJD 173:134–145, 2015; CD 30+ CTCL (Ki+anaplastic large cell lymphoma) – isolated red nodule Ann Oncol 5(Suppl.1)25–30, 1994; primary B-cell lymphoma AD 130: 1551–1556, 1994; primary cutaneous diffuse large B-cell lymphoma, leg type; Bcl-2 expression – red to bluish nodules of one or both legs and ankles JAAD 69:329–340, 2013; JAAD 66:650–654, 2012; BJD 160:713–716, 2009; AD 143:1520–1526, 2007; AD 143:1144–1150, 2007; and primary cutaneous large B-cell lymphoma of the legs AD 132:1304–1308, 1996; large cell B-cell lymphoma of the leg JAAD 49:223–228, 2003; primary cutaneous marginal zone B-cell lymphoma – red nodules with surrounding erythema or pink papules or nodules BJD 176:1010–1020, 2017; JAMADerm 150:412–418, 2014; JAAD 59:179–1206, 2008; AD 141:1139–1145, 2005; BJD 147:1147–1158, 2002; intravascular B-cell (malignant angioendotheliomatosis) lymphoma mimicking erythema nodosum J Cutan Pathol 27:413–418, 2000; JAAD 39:318–321, 1998; Cancer 3:1738–1745, 1994; intravascular lymphoma – painful gray-brown, red, blue-livid patches, plaques, nodules, with telangiectasia and underlying induration; 40% of patients with intravascular lymphoma present with cutaneous lesions BJD 157:16–25, 2007; angiotropic B-cell lymphoma (malignant angioendotheliomatosis); lymphoplasmacytic lymphoma JAAD 38:820–824, 1998; plasmablastic lymphoma (HIV- and EBVassociated) – skin-colored-pink, purple nodules of legs JAAD 58:676–678, 2008; follicular-center B-cell lymphoma – nodules of face, scalp, trunk, extremities AD 132:1376–1377, 1996; immunocytoma (low grade B- cell lymphoma) – reddish-brown papules, red nodules, plaques and/or tumors on the extremities JAAD 44:324– 329, 2001; CD56+ lymphoma AD 140:427–436, 2004; HTLV-1 lymphoma BJD 128:483–492, 1993; Am J Med 84:919–928, 1988; plasmacytoid dendritic cell neoplasm (lymphoblastoid natural killer-cell lymphoma) – purple nodule of leg; nodule of face or scalp BJD 162:74–79, 2010; BJD 146:148–153, 2002; histiocytic lymphoma (reticulum cell sarcoma) – blue-­red nodules Am J Dermatopathol 14:511–517, 1992; Cancer 62:1970–1980, 1988; Epstein-Barr virus and natural killer T-cell lymphoma JAAD 59:157– 161, 2008; cutaneous Richter syndrome (CLL rapidly developing into large cell lymphoma) BJD 140:708–714, 1999; Clin Exp Dermatol 18:263–267, 1993; Am J Med 68:539–548, 1980; primary cutaneous marginal zone B-cell lymphoma JAAD 69:329–340, 2013; on back BJD 157:591–595, 2007; in children BJD 161:140–147, 2009; plasmablastic post-transplant lymphoproliferative disorder Ped Derm 26:713–716, 2009; anetodermic primary cutaneous B-cell lymphoma – associated with anti-phospholipid antibodies AD 146:175– 182, 2010; Arthritis Rheum 36:133–134, 2010; Clin Exp Dermatol 31:130–131, 2006; Actas Dermosifiligr 94:243–246, 2003; Am J Dermatopathol 23:124–132, 2001; BJD 143:165–170, 2000; angioimmunoblastic T-cell lymphoma (angioimmunoblastic lymph-

Nodules, Red, Extremities adenopathy with dysproteinemia) – morbilliform eruption; arthralgias, purpura, petechiae, urticaria, nodules JAAD 65:855–862, 2011; NEJM 361:900–911, 2009; BJD 144:878–884, 2001; JAAD 36:290–295, 1997; JAAD 1:227–32, 1979; metastatic testicular lymphoma JAAD 66:650–654, 2012; primary cutaneous diffuse large cell B-cell lymphoma, leg type – red-violaceous sporotrichoid nodules of leg AD 148:1199–1204, 2012; primary cutaneous follicular center B-cell lymphoma JAAD 69:343–354, 2013; cutaneous extranodal natural killer T-cell lymphoma – multiple violaceous or red nodules of extremities, subcutaneous nodules, cellulitis, abscess-like lesions JAAD 70:1002–1009, 2014; HTLV-1 leukemia/ lymphoma – nodulotumoral lesions, nodules, ulcerated nodules, multipapular lesions, red plaques, red patches, erythroderma JAAD 72:293–301, 2015; Richter transformation – transformation of chronic lymphocytic leukemia to high grade lymphoma – red nodules and plaques of arm with generalized lymphadenopathy BJD 172:513–521, 2015; primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma – necrotic nodules BJD 173:869–871, 2015; cutaneous peripheral T-cell lymphoma JAAD 75:992–999, 2016; multifocal primary cutaneous anaplastic large cell lymphoma BJD 179:724–731, 2018 Lymphomatoid granulomatosis (angiocentric lymphoma) – violaceous nodules Ped Derm 17:369–372, 2000 Lymphomatoid papulosis JAAD 49:1049–1058, 2003; red nodule with scale AD 147:943–947, 2011 Malignant fibrous histiocytoma Cutis 69:211–214, 2002 Malignant histiocytosis – single red or violaceous nodules or diffuse papulonodular eruption of legs and/or buttocks JAAD 56:302–316, 2007; Hum Pathol 15:368–377, 1984 Malignant nodular hidradenoma (aka clear cell eccrine carcinoma, clear cell hidradenocarcinoma, malignant acrospiroma, malignant clear cell acrospiroma, malignant clear cell hidradenoma, malignant clear cell myoepithelioma, solid cystic hidradenocarcinoma) – nodule of head, trunk, distal extremities Cutis 68:273–278, 2001; deep red nodule of leg Cutis 88:173–174, 2011 Malignant schwannoma Melanocytic nevus – congenital nevus presenting as proliferative red nodule without underlying pigmentation BJD 176:1131–1143, 2017; Society Pediatric Dermatology Annual Meeting, July, 2015 Melanoma, including amelanotic melanoma NEJM 368:1536, 2013; AD 144:560–561, 2008; Semin Oncol 2:5–118, 1975; metastatic uveal melanoma BJD 169:160–161, 2013; spitzoid melanoma – purple nodule of leg Cutis 90:180,187–188, 2012 Merkel cell carcinoma – red nodule of arm Cutis 87:81–84, 2011; red nodules of legs JAAD 81:1–21, 2019; J Drugs in Dermatol 9:779–784, 2010; Cutis 90: 183–185, 2012; Dermatol Ther 21:447–451, 2008; JAAD 58:375–381, 2008; violaceous nodule of knee AD 145:715–720, 2009 Metaplastic synovial cysts – red nodules of buttocks JAAD 41:330–332, 1999 Metastases – testicular carcinoma JAAD 65:455–456, 2011 Multiple myeloma JAAD 76:S71–72, 2017; AD 139:475–486, 2003 Muscle tumors – primary or metastatic tumors of muscle; palpable painful mass of thigh

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Neurofibroma Neurothekeoma Ped Derm 37:187–189, 2020; AD 139:531–536, 2003 Nevus comedonicus, inflammatory JAAD 38:834–836, 1998 Nodular hidradenoma (clear cell hidradenoma, eccrine acrospiroma, clear cell myoepithelioma) AD 136:1409–1414, 2000; JAAD 42:693–695, 2000 Nodular subepidermal fibroma Cutis 69:173–174, 2002 Peripheral neuroepithelioma Curr Prob Derm 14:41–70, 2002 Pilar cyst Pilomatrixoma Cutis 69:173–174, 2002 Plasmacytoma – extramedullary plasmacytoma – violaceous brown nodule JAAD 49:S255–258, 2003; primary plasmacytoma JAAD 38:820–834, 1998; trauma-induced secondary cutaneous plasmacytoma AD 146:1301–1306, 2010 Plasmacytosis, systemic JAAD 38:629–631, 1998 Porocarcinoma AD 136:1409–1414, 2000 Poroid hidradenoma – painful deep red, blue, brown or violaceous nodule of arm, scalp, face, or trunk Ped Derm 28:60–61, 2011; AD 146:557–562, 2010 Post-transplantation lymphoproliferative disorder – annular violaceous nodules JAMADerm 155:619–620, 2019; JAAD 72: 1016–1020, 2015; JAAD 54:657–663, 2006; JAAD 52:S123–124, 2005; AD 140:1140–1164, 2004; JAAD 51:778–780, 2004 Primary cutaneous perivascular epithelioid cell tumor – red nodule of legs and abdomen JAAD 71:1127–1136, 2014 Progressive eruptive histiocytomas (brown) JAAD 35:323–325, 1996 Rhabdomyosarcoma Soft tissue sarcoma Solitary fibrous tumor – purple nodule of thigh, scalp or face AD 142:921–926, 2006 Spitz nevus – BAP-1 loss in epithelioid Spitz nevus Squamous cell carcinoma – complicating venous stasis ulcers South Med J 58:779–781, 1965; complicating non-Herlitz junctional epidermolysis bullosa – beefy red nodules JAAD 65:780–789, 2011 Stewart-Treves lymphosarcoma – personal observation Subcutaneous myeloid sarcoma AD 141:104–106, 2005 Transplantassociated hematolymphoid neoplasm – p16 hypermethylation and Epstein-Barr virus infection; skin colored nodules; red nodules of legs JAAD 55:794–798, 2006 Syringofibroadenoma – multiple erythematous nodules of legs; associated with chronic skin ulcers, burn scars, venous stasis, elephantiasis, lepromatous neuropathy Skin and Allergy News, Sep 2014; pp.35

PARANEOPLASTIC DISEASES Eosinophilic dermatosis of myeloproliferative disease – face, scalp; scaly red nodules; trunk – red nodules; extremities – red nodules and hemorrhagic papules AD 137:1378–1380, 2001

Myelodysplastic syndromes – prurigo nodularis-like lesions JAAD 33:187–191, 1995; neutrophilic panniculitis BJD 136:142–144, 1997

Erythema nodosum associated with acute myelogenous leukemia, chronic myelogenous leukemia, chronic myelomonocytic leukemia

Myeloid sarcoma, de novo – diffuse red-brown nodules Ped Derm 36:509–510, 2019

Exaggerated arthropod bite reactions – chronic lymphocytic leukemia

Myoepithelioma, cutaneous AD 147:499–504, 2011

Necrobiotic xanthogranuloma with paraproteinemia Medicine (Baltimore) 65:376–388, 1986

Myofibromatosis Nerve sheath myxoma AD 145:195–200, 2009

738 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Neutrophilic panniculitis of myelodysplasia – red nodules of legs and soles; MYSM1 deficiency; short stature Ped Derm 36:258–259, 2019; JAAD 50:280–285, 2004 Pancreatic panniculitis – pancreatic carcinoma Cutis 80:289–294, 2007; acinar cell carcinoma – fever and arthritis Cutis 91:186–190, 2013 Paraneoplastic septal panniculitis associated with acute myelogenous leukemia BJD 144:905–906, 2001 Paraneoplastic vasculitis – nodules, panniculitis J Rheumatol 18:721–727, 1991 Polyarteritis nodosa – associated with hairy cell leukemia, and chronic myelomonocytic leukemia Thrombophlebitis migrans (Trousseau’s sign) – association with internal malignancy Circulation 22:780, 1960

1994; Behcet’s disease JAAD 41:540–545, 1999; NEJM 341:1284– 1290, 1999; neutrophilic eccrine hidradenitis Cutis 68:107–111, 2001 CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) – fever, recurrent annular violaceous plaques and nodules, violaceous eyelid edema, low weight and height, lipodystrophy, hepatosplenomegaly, and inflammation Ped Derm 26:654, 2009 Congenital self-healing reticulohistiocytosis – Hashimoto-Pritzker type AD 134:625–630, 1998 DADA2 (deficiency of adenosine deaminase 2) – autosomal recessive; recurrent fevers, early onset stroke, livedo racemosa, polyarteritis nodosa, hepatosplenomegaly; mutation in CECR1 JAAD 75:449–453, 2016 Disseminated lipogranulomatosis (Farber’s disease)

Thrombosed veins at IV sites with squamous cell carcinoma of the kidney – personal observation

Familial Mediterranean fever – panniculitis AD 134:929–931, 1998; erythema nodosum-like lesions AD 112:364–366, 1976; neutrophilic lobular panniculitis – subcutaneous red nodules of extremities with contusiform changes JAMADerm 150:213–214, 2014

PRIMARY CUTANEOUS DISEASE

Farber’s disease (lipogranulomatosis) – deformed or stiff joints with painful limb contractures and red periarticular subcutaneous nodules Ped Derm 26:44–46, 2009; Eur J Ped 157:515–516, 1998; AD 130:1350–1354, 1994

Anetoderma of Jadassohn AD 102:697–698, 1970 Epidermolysis bullosa pruriginosa – dominant dystrophic or recessive dystrophic; mild acral blistering at birth or early childhood; violaceous papular and nodular lesions in linear array on shins, forearms, trunk; lichenified hypertrophic and verrucous plaques in adults, reticulate scarring, dermatitis with lichenified plaques, violaceous linear scars, albopapuloid lesions of the trunk, prurigo nodularis-like lesions, milia Ped Derm 26:115–117, 2009; BJD 152:1332–1334, 2005; BJD 146:267–274, 2002; BJD 130:617–625, 1994 Epidermolysis bullosa – junctional epidermolysis bullosa – abnormal teeth with papular prurigo-like lesions BJD 169:195–198, 2013 Erythema elevatum diutinum Cutis 68:41–42, 55, 2001; Cutis 34:41–43, 1984 Granuloma annulare Keratosis lichenoides chronica – extremities and buttocks JAAD 38:306–309, 1998; JAAD 37:263–264, 1997; AD 131:609–614, 1995; AD 105:739–743, 1972 Nodular erythrocyanosis – calves, knees, thighs, buttocks of women with paralysis Prurigo nodularis – idiopathic or associated with lymphoma, peripheral T-cell lymphoma (Lennert’s lymphoma) Cutis 51:355– 358, 1993; Hodgkin’s disease Dermatologica 182:243–246, 1991; Ped Derm 7:136–139, 1990; gluten sensitive enteropathy BJD 95:89–92, 1976; AIDS JAAD 33:837–838, 1995; uremia South Med J 68:138–141, 1975; depression, liver disease, alpha-1 antitrypsin deficiency Australas J Dermatol 32:151–157, 1991; malabsorption Dermatologica 169:211–214, 1984

PSYCHOCUTANEOUS DISEASES

Fibrodysplasia ossificans progressiva Hemophagocytic lymphohistiocytosis syndrome AD 128:193–200, 1992 Histiophagocytic syndrome – panniculitis Ryumachi 41:31–36, 2001; Ann DV 128:1339–1342, 2001; J Rheumatol 26:927–930, 1999 Hypereosinophilic syndrome – red macules, red papules, plaques, and nodules, urticaria, angioedema Allergy 59:673–689, 2004; Am J Hematol 80:148–157, 2005; AD 132:535–541, 1996; Medicine 54:1–27, 1975 Hyper IgD syndrome – red macules or papules, urticaria, red nodules, combinations of fever, arthritis, and rash, annular erythema, and pustules – autosomal recessive; mevalonate kinase deficiency AD 136:1487–1494, 2000; AD 130:59–65, 1994 Hyper IgM syndrome – X-linked; sarcoid-like granulomas; multiple papulonodules of face, buttocks, arms Ped Derm 21:39–43, 2004 IgG4 disease – papules, plaques, nodules, parotid gland swelling (parotitis), lacrimal gland swelling, dacryoadenitis, sialadenitis, proptosis, idiopathic pancreatitis, retroperitoneal fibrosis, aortitis JAAD 75:197–202, 2016 IPEX syndrome – X-linked; immune dysregulation, polyendocrinopathy (diabetes mellitus, thyroiditis), autoimmune enteropathy; mutation of FOXP3 gene encodes DNA-binding protein that suppresses transcription of multiple genes involved in cytokine production and T cell proliferation; atopic-like or nummular dermatitis, urticaria, scaly psoriasiform plaques of trunk and extremities, penile rash, alopecia universalis, trachyonychia, bullae; pemphigoid nodularis (bullae and prurigo nodularis) JAAD 55:143–148, 2006; AD 140:466–472, 2004; J Pediatr 100:731–737, 1982 Nakajo syndrome – nodular erythema with digital changes

Factitial panniculitis – lipomembranous traumatic panniculitis with overlying hypertrichosis SKINmed 12:127–130, 2014

Neurofibromatosis type 1

SYNDROMES

Relapsing polychondritis – panniculitis Dermatology 193:266–268, 1996

Behcet’s disease – erythema nodosum-like lesions (superficial vein thrombophlebitis extending to subcutaneous fat) AD 145:171–175, 2009; BJD 159:555–560, 2008; BJD 147:331–336, 2002; JAAD 40:1–18, 1999; JAAD 36:689–696, 1997; Ped Derm 11:95–101, 1995; subcutaneous red nodules (vasculitis) JAAD 31:493–495,

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy JAAD 56:302–316, 2007; Arch Pathol 87:63–70, 1969

Noonan’s syndrome – multiple granular cell tumors (pink nodules) Ped Derm 27:209–211, 2010

Sweet’s syndrome JAAD 31:535–536, 1994; septal erythema nodosum-like panniculitis AD 121:785–788, 1985; subcutaneous

Nodules, Red, Extremities Sweet’s syndrome AD 138:1551–1554, 2002; Ann DV 128:641–643, 2001; BJD 136:142–144, 1997; JAAD 23:247–249, 1990; subcutaneous Sweet’s syndrome associated with myeloid disorders JAAD 68:1006–1015, 2013

TRAUMA

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Intravascular microemboli from polymer coats of intravascular device – hemorrhagic panniculitis presenting as ecchymosis; nodules of buttocks, arms, and trunk JAMADerm 151:204–207, 2015 Intravascular papillary endothelial hyperplasia – pseudo-Kaposi’s sarcoma – red or purple papules and nodules of the legs JAAD 10:110–113, 1984 Lipodermatosclerosis, acute JAAD 35:566–568, 1996

Athletes’ nodules – pink-red nodules (collagenomas) above ankles AD 143:417–422, 2007

Leukocytoclastic vasculitis – subcutaneous red nodules JAAD 31:493–495, 1994

Carpenter’s calluses – personal observation

Lymphocytic thrombophilic arteritis – painless non-ulcerating livedo reticularis, reticulated hyperpigmentation, red nodules AD 144:1175–1182, 2008

Cold panniculitis – in two month old – red nodules of back and legs Ped Derm 34:614–615, 2017; including equestrian cold panniculitis in women AD 116:1025–1027, 1980; cold panniculitis from ice packs Cutis 95:21–24, 2015 Hematoma – palpable painful mass of thigh Intravenous drug abuse (IVDA) – tracks Islamic prayer nodules of knees – personal observation Lymphoid hyperplasia secondary to cat scratches – red subcutaneous nodules Ped Derm 27:294–297, 2010

Lymphostasis verrucosa cutis – personal observation Malignant angioendotheliomatosis (intravascular lymphomatosis) – red to purple nodules and plaques on trunk and extremities with prominent telangiectasias over lesions JAAD 38:143–175, 1998 Multifocal lymphangioendotheliomatosis with thrombocytopenia – red-brown plaques, nodules, and tumors JAAD 67:898–903, 2012 Necrotizing vasculitis Nodular vasculitis (leukocytoclastic vasculitis) JAAD 45:163–183, 2001

VASCULAR DISEASES Angiokeratoma circumscriptum Angiosarcoma – purple nodules BJD 138:692–694, 1998; AD 124:263–264, 266–267, 1988 Arteriovenous fistulae – congenital or acquired; red pulsating nodules with overlying telangiectasia – extremities, head, neck, trunk Benign (reactive) angioendotheliomatosis – red-brown or violaceous nodules on arms or legs JAAD 38:143–175, 1998 Cholesterol emboli JAAD 55:786–793, 2006; BJD 146:511–517, 2002; Medicine 74:350–358, 1995; Angiology 38:769–784, 1987; AD 122:1194–1198, 1986 Eosinophilic granulomatosis with polyangiitis – elbow nodules JAAD 37:199–203, 1997; subcutaneous red nodules (vasculitis) JAAD 31:493–495, 1994 Cutaneous polyarteritis nodosa – atrophie blanche lesions, acrocyanosis, Raynaud’s phenomenon, peripheral gangrene, red plaques and peripheral nodules, myalgias; macular lymphocytic arteritis – red or hyperpigmented reticulated patches of legs JAAD 73:1013–1020, 2015 Deep vein thrombophlebitis – personal observation Degos’ disease – red papules with yellow centers JAAD 38:852– 856, 1998; Ann DV 79:410–417, 1954 Epithelioid angiosarcoma – red nodule of leg JAAD 38:143–175, 1998 Epithelioid hemangioendothelioma – purple subcutaneous nodule of forearm JAAD 58:519–521, 2008

Non-involuting capillary hemangioma (NICH) – red patch; blue patch; red nodules JAAD 70:899–903, 2014; large purple tumor Ped Derm 29:182–185, 2012 Papillary intralymphatic angioendothelioma/retiform hemangioendothelioma spectrum – subcutaneous purple nodules or deep red plaques BJD 171:474–484, 2014; Cancer 24:503–510, 1969 Perniosis – due to cold therapy system; red nodules of legs AD 148:1101–1102, 2012 Polyarteritis nodosa, systemic BJD 159:615–620, 2008; Ann Int Med 89:66–676, 1978; cutaneous infarcts presenting as tender nodules; cutaneous (microscopic polyangiitis) (livedo with nodules) – painful or asymptomatic red or skin colored multiple nodules with livedo reticularis of feet, legs, forearms face, scalp, shoulders, trunk BJD 159:615–620, 2008; JAAD 53:724–728, 2005; BJD 146:694–699, 2002; Ped Derm 15:103–107, 1998; Ann Rheum Dis 54:134–136, 1995; AD 130:884–889, 1994; JAAD 31:561–566, 1994; JAAD 31:493–495, 1994; Acta Med Scand 76:183–225, 1931; cutaneous associated with Crohn’s disease Dis Colon Rectum 23:258–262, 1980; familial polyarteritis nodosa of Georgian Jewish, German, and Turkish ancestry – oral aphthae, livedo reticularis, leg ulcers, Raynaud’s phenomenon, digital necrosis, nodules, purpura, erythema nodosum; systemic manifestations include fever, myalgias, arthralgias, gastrointestinal symptoms, renal disease, central and peripheral neurologic manifestations; mutation in adenosine deaminase 2 (CECR1) NEJM 370:921–931, 2014 Post-thrombotic periphlebitis Pustular vasculitis of hands JAAD 32:192–198, 1995; JAAD 31:493–495, 1994 Pyogenic granuloma

Erythema induratum of Whitfield (nodular vasculitis) – nodules with edematous ankles

Retiform hemangioendothelioma – exophytic masses of arms or legs JAAD 38:143–175, 1998

Erythrocyanosis – may have ulceration, erythema, keratosis pilaris, desquamation, nodular lesions, edema, and fibrosis

Spindle cell hemangioendothelioma – purple nodule Cutis 53:134– 136, 1994

Fat emboli

Superficial migratory thrombophlebitis – oval tender red nodules of the legs, abdomen, arms JAAD 45:163–183, 2001; JAAD 23:975– 985, 1990; associated with acute pancreatitis – personal observation; reticulated hyperpigmented patches with red subcutaneous nodules Cutis 101:322,325–326, 2018

Glomus tumor, solitary – painful pink, purple nodule Ann Plast Surg 43:436–438, 1999 Granulomatosis with polyangiitis – subcutaneous red nodules JAAD 31:493–495, 1994 Infantile hemangioma with minimal or arrested growth Ped Derm 36:125–131, 2019

Superficial thrombophlebitis Takayasu’s arteritis – subcutaneous red nodules JAAD 31:493–495, 1994

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Temporal arteritis – granulomatous lipophagic panniculitis Ann Rheum Dis 51:812–814, 1992 Thromboangiitis obliterans (Buerger’s disease) – palpable painful mass of thigh; superficial thrombophlebitis (leg nodule); acute thrombophlebitis; red nodules of sides of feet and lateral legs; associated with peripheral arterial disease Am J Med Sci 136:567–580, 1908 Thrombophlebitis, idiopathic – livid painful nodules NEJM 344:1222–1231, 2001 Tufted angioma – red nodule Ped Derm 35:808–816, 2018; AD 142:745–751, 2006; Ped Derm 19:394–401, 2002; JAAD 20:214– 225, 1989 Vasculitis – large and/or small vessel – leukocytoclastic vasculitis; urticarial vasculitis AD 134:231–236, 1998 Venous thrombosis – swelling and pain of calf NEJM 344:1222– 1231, 2001; BMJ 320:1453–1456, 2000

NODULES, RED, FACE  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Chronic granulomatous disease – granulomas, furuncles, suppurative nodules NEJM 317:687–694, 1987

Halogenoderma Hyaluronic acid plus dextranomer microparticles (Matridex), injectable JAAD 64:1–34, 2011 Paraffinoma – facial nodules and eyelid edema JAAD 56:S127–128, 2007; nodule of glabella with recurrent facial edema; hepatosplenomegaly, pulmonary fibrosis AD 148:385–390, 2012 Self-injection with dermal fillers BJD 172:782–783, 2015 Silica granulomas from mine explosion – red nodules of face, neck, chest JAMADerm 154:953–954, 2018 Silicone gel, injectable – red nodule of chin JAAD 64:1–34, 2011

INFECTIONS Abscess, carbuncle, furuncle Actinomycosis, cervicofacial – nodule of cheek or submaxillary area; board-like induration; multiple sinuses with puckered scarring; sulfur granules discharged Arch Int Med 135:1562–1568, 1975 African blastomycosis Anthrax Bacillary angiomatosis Bejel Botryomycosis

Hyper IgD syndrome – recurrent transient and fixed pink plaques and nodules of face and extremities; cephalic pustulosis; mevalonate kinase deficiency Ped Derm 35:482–485, 2018

Candida sepsis – papules and nodules with pale centers Am J Dermatopathol 8:501–504, 1986; JAMA 229:1466–1468, 1974

Lupus erythematosus – discoid lupus erythematosus; lupus profundus (lupus panniculitis) AD 122:576, 1986; AD 103:231–242, 1971

Coccidioidomycosis AD 144:933–938, 2008; JAAD 46:743–747, 2002; An Circulo Med Argent 15:585–597, 1892; crateriform nasal nodule AD 146:789–794, 2010

CONGENITAL LESIONS Microcystic adnexal carcinoma Ped Derm 28:35–38, 2011 Nasal glioma – midline nasal nodule Dermatol Therapy 18:104–116, 2005 Neuroglial heterotopia (encephaloceles that lost intracranial connection) – red nodule of nasal root; skin colored nodule; red blue firm non-compressible nodule (nasal glioma); intranasal polypoid masses; and rudimentary or atretic encephaloceles Ped Derm 32:161–170, 2015

DRUG-INDUCED Anti-PD-1 therapy – lichen planus follicularis tumidus JAMADerm 155:1197–1198, 2019 Bortezomib (proteasome inhibitor for treatment of myeloma) – red nodules of trunk, face, neck, and extremities JAAD 55:897–900, 2006

Chromomycosis – Aureobasidium pullulans AD 133:663–664, 1997

Cryptococcosis – umbilicated nodule NEJM 370:1741, 2014; Clin Inf Dis 33:700–705, 2001 Demodicidosis – nodulocystic lesions of face BJD 170:1219–1225, 2014 Dental sinus – ulcerated nodule of lower cheek Ped Derm 27:410– 411, 2010 Dracunculosis Ecthyma Emmonsia pasteuriana – dimorphic fungus; disseminated infection in South Africa; lichenoid diffuse papulosquamous eruption; crusted verrucous facial nodules and plaques NEJM 369:1416–1424, 2013 Epstein-Barr virus (HHV4) – primary cutaneous Epstein-Barr virus-related lymphoproliferative disorders; violaceous nodule JAAD 58:74–80, 2008 Erysipelas Fusarium – sepsis; red nodule with central pallor Rhinology 34(4):237–241, 1996

Drug-induced pseudolymphoma syndrome JAAD 38:877–905, 1998

Gnathostomiasis – migratory tender red nodules JAAD 68:301–305, 2013

Ipilimumab – reactivation of dermal filler foreign body reaction after treatment with ipilimumab BJD 175:1351–1353, 2016

Herpes simplex – pseudolymphoma appearance – violaceous nodule Am J Dermatopathol 13:234–240, 1991

Voriconazole-induced squamous cell carcinomas Clin Inf Dis 58:839,901–902, 2014

Insect bite Kerion Lacrimal gland abscess – adjacent to medial canthus

EXOGENOUS AGENTS BCG granuloma Bromoderma – multiple red nodules of forehead, upper back, arms, and legs BJD 158:427–429, 2008 Foreign body granuloma AD 139:17–20, 2003

Leishmaniasis – acute cutaneous leishmaniasis JAMADerm 150:201–202, 2014; Clin Inf Dis 33:815,897–898, 2001; J Clin Inf Dis 22:1–13, 1996; AD 128:83–87, 1992; L. tropica – ulcerated nodule of face JAAD 71:271–277, 2014; JAAD 53:810–815, 2005; post-kalaazar dermal leishmaniasis BJD 165:411–414, 2011; BJD 163:870– 874, 2010; ulcerated facial nodules JAAD 73:897–908, 2015

Nodules, Red, Face Leprosy – lepromatous leprosy; Souza Campos nodule of leprosy JAAD 54:559–578, 2006; subcutaneous lepromas Rook p.1224– 1227, 1998, Sixth Edition; erythema nodosum leprosum (vasculitis) – painful facial nodules with fever, arthralgias, dactylitis, iritis, uveitis, orchitis, adenitis, glomerulonephritis, tibial periostitis; ulcerated nodules JAAD 83:17–30, 2020; JAAD 51:416–426, 2004; AD 138:1607–1612, 2002; histoid leprosy – centrofacial distribution BJD 160:305–310, 2009

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23:462–467, 1996; tertiary (gumma); ulcerated nodules of face – malignant secondary syphilis JAMADerm 152:829–830, 2016; AD 99:70–73, 1969; BJD 9:11–26, 1897 Tropical ulcer Tularemia Warts Yaws

Milker’s nodule Molluscum contagiosum, giant Mycobacterium abscessus – facial nodules after soft tissue augmentation Dermatol Surg 29:97–973, 2003 Mycobacterium avium-intracellulare – cervicofacial lymphadenitis in children Ped Derm 21:24–29, 2004

INFILTRATIVE DISORDERS Amyloidosis – nodular primary localized cutaneous amyloidosis JAAD 57:S26–29, 2007 Cutaneous lymphoid hyperplasia JAAD 65:112–124, 2011

Mycobacterium chelonae – facial lesions; red papules and nodules BJD 170:471–473, 2014

Hashimoto-Pritzker disease (congenital self-healing reticulohistiocytosis) – red facial nodule JAAD 53:838–844, 2005

Mycobacterium malmoense – cervicofacial lymphadenitis in children Ped Derm 21:24–29, 2004

IgG4-related skin disease – plasma cells and fibrosis; FoxP3+ cells JAMA Derm 149:742747, 2013

Mycobacterium marinum

Jessner’s lymphocytic infiltrate

Mycobacterium mucogenicum – following cosmetic use of poly-Llactic acid SKINmed 12:353–357, 2013; red nodule of medial canthus following dacryocystorhinostomy and Cranford tube replacement JAMADerm 150:981–983, 2014

Juvenile xanthogranuloma – personal observation

Mycobacterium scrofulaceum – ulcerated nodule of cheek Ped Derm 22:476–479, 2005 Mycobacterium tuberculosis – scrofuloderma – infected lymph node, bone, joint, lacrimal gland with overlying red-blue nodule which breaks down, ulcerates, forms fistulae, scarring with adherent fibrous masses which may be fluctuant and draining BJD 134:350– 352, 1996; BCG granuloma; lupus vulgaris Myiasis – cuterebrid myiasis Ped Derm 21:515–516, 2004; Hypoderma tarandi; bumblebee-like fly of subarctic regions; eggs deposited on reindeer (caribou); larvae penetrate skin, hatch, and result in migratory swellings; ophthalmomyiasis may result in blindness NEJM 367:2456–2457, 2012

Lymphocytoma cutis – personal observation Progressive nodular histiocytosis – dermal dendrocytes; red nodules of face, trunk, and extremities BJD 143:628–631, 2000 Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) – multiple multilobular red nodules with yellow centers JAMA Derm 149:992–994, 2013; BJD 164:213–215, 2011; AD 144:120–121, 2008 Sea blue histiocytosis – facial macular brown hyperpigmentation; nodules of face, trunk, hands, and feet; eyelid infiltration; puffy face; leonine facies JAAD 57:1031–1045, 2007

Nocardiosis, primary cutaneous AD 146:81–86, 2010

Self-healing juvenile cutaneous mucinosis – red nodules of face, scalp, hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973

North American blastomycosis – pustulonodular infiltration of nose JAMA 312:2564–2565, 2014; disseminated – red facial scaly nodule Ped Derm 35:673–675, 2018; NEJM 356:1456–1462, 2007

INFLAMMATORY DISORDERS

Onchocerciasis (Onchocerca volvulus) – facial nodules JAAD 73:929–944, 2015 Orf Clin Dermatol 32:715–733, 2014; JAAD 40:815–817, 1999 Paecilomyces lilacinus – red nodules with necrotic centers Ann Int Med 125:799–806, 1996

Erythema nodosum in children Ped Derm 13:447–450, 1996 Febrile idiopathic lobar panniculitis of childhood – abdominal pain, arthralgia, fever, red nodules of face, legs, trunk, lipoatrophy Ped Derm 31:652, 2014

Paracoccidioidomycosis JAAD 53:931–951, 2005

Idiopathic aseptic facial granuloma – purple facial nodules in infants and toddlers Ped Derm 35:397–400, 2018; Ped Derm 35:490–493, 2018

Preauricular cyst Curr Prob in Dermatol 13:249–300, 2002

Hidradenitis suppurativa – personal observation

Pseudomonas sepsis JAAD 32:279–280, 1995; Am J Med 80:528–529, 1986

Idiopathic facial granuloma of children – red or violaceous nodule of cheek Ped Derm 31:729–730, 2014; Ped Derm 30:394–395, 2013

Rhinoscleroma (Klebsiella pneumonia subspecies rhinoscleromatis) – facial perioral nodule JAAD 69:1066–1067, 2013

Lymphocytoma cutis (cutaneous lymphoid hyperplasia) AD 142:1561–1566, 2006; Cancer 69:717–724, 1992; Acta DV (Stockh)62:119–124, 1982; eyebrow nodule Ped Derm 30:628–629, 2013

Papular urticaria

Scabies – in elderly and infants JAAD 82:533–548, 2020 Sporotrichosis, fixed cutaneous Cutis 54:279–286, 1994; Dermatologica 172:203–213, 1986; Sporothrix schenckii var brasiliensis – red nodule of cheek with conjunctivitis BJD 172:1116– 1119, 2015 Staphylococcus aureus – abscess (furuncle) Rook p.1119, Sixth Edition Syphilis – nodular secondary JAAD 82:1–14, 2020; AD 133:1027– 1032, 1997; in AIDS Clin Dermatol 38:152–159, 2020; J Clin Inf Dis

Nodular fasciitis AD 137:719–721, 2001 Panniculitis – personal observation Pseudolymphomatous folliculitis – solitary red dome shaped or flat elevated nodule of cheek, nose, eyelid, forehead Am J Surg Pathol 23:1313–1319, 1999; Am J Pathol 24:367–387, 1948; differential diagnosis includes T cell-rich B-cell lymphoma, primary cutaneous follicular center lymphoma, folliculotropic CTCL, cutaneous B-cell

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lymphoid hyperplasia, cutaneous T-cell pseudolymphoma, granulomatous rosacea

Epithelioid fibrohistiocytoma – red nodule of nose Ped Derm 35:678–680, 2018

Cutaneous Rosai-Dorfman disease – facial nodules JAMADerm 150:787–788, 2014

Hidradenocarcinoma, metastases – red nodules of face and scalp AD 147:998–999, 2011

Sarcoid – lupus pernio JAAD 48:290–293, 2003; JAAD 16:534–540, 1987; BJD 112:315–322, 1985; Clin Exp Dermatol 9:614–617, 1984

Hidrocystoma

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) – violaceous, red papules and nodules; cervical lymphadenopathy; also axillary, inguinal, and mediastinal adenopathy JAAD 41:335–337, 1999; Int J Derm 37:271–274, 1998;

Kaposi’s sarcoma

Am J Dermatopathol 17:384–388, 1995; Cancer 30:1174–1188, 1972 Subcutaneous fat necrosis of the newborn AD 134:425–426, 1998

Infantile myofibromatosis AD 134:625–630, 1998 Keloids Keratoacanthoma – giant keratoacanthoma in xeroderma pigmentosum – personal observation Leiomyoma (pilar), congenital JAAD 59:S102–104, 2008 Leukemia, including congenital monocytic leukemia; monocytic leukemia – red, brown, violaceous nodule AD 123:225–231, 1971

METABOLIC DISEASES

Lipoma, including subgaleal lipoma – personal observation

Blueberry muffin baby in hereditary spherocytosis – red nodules, generalized Cutis 101:111–114, 2018

Lymphadenoma – preauricular red nodule AD 141:633–638, 2005

Verrucous xanthoma – nodule of nose J Laryngol Otol 113:79–81, 1999; Am J Dermatopathol 8:237–240, 1986

NEOPLASTIC DISEASES Adenoid cystic carcinoma Angiolipoma Apocrine hidrocystoma AD 137:657–662, 2001 Atypical fibroxanthoma AD 137:719–721, 2001; Cutis 51:47–48, 1993; BJD 97:167, 1977; Cancer 31:1541–1552, 1973; Tex St J Med 59:664–667, 1963 Basal cell carcinoma Acta Pathol Microbiol Scand 88A:5–9, 1980; basal cell carcinomas in nevoid basal cell carcinoma syndrome JAAD 55:S86–89, 2006 Benign nodular hidradenoma AD 140:609–614, 2004 Blastic plasmacytoid dendritic cell neoplasm – “purple plum” nodule of face BJD 169:579–586, 2013 Carcinosarcoma (basal cell carcinoma with sarcomatous component) JAAD 59:627–632, 2008 CD4 + CD56+ hematodermic neoplasm – vascular nodule of forehead; red plaques of face; tumor of plasmacytoid dendritic cells Cutis 89:278–283, 2012 Chondroid syringoma AD 84:835–847, 1961; purple nodule AD 140:751–756, 2004 Clear cell hidradenoma (eccrine acrospiroma) Combined squamous cell carcinoma and Merkel cell carcinoma – crusted papule, red facial nodule, red papule, red nodule of wrist JAAD 73:968–975, 2015 Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease) Int J Dermatol 38:693–696, 1999 Cylindroma Am J Dermatopathol 17:260–265, 1995 Dermal duct tumor – red nodule of head, neck, arms, legs, or back AD 140:609–614, 2004 Dermatofibrosarcoma protuberans Dermatol Ther 21:428–432, 2008 Eccrine porocarcinoma Dermatol Ther 21:433–438, 2008 Eccrine poroma Eccrine sweat gland carcinoma – face, scalp, palm J Cutan Pathol 14:65–86, 1987 Embryonal rhabdomyosarcoma Ped Derm 15:403–405, 1998 Epidermoid cyst, ruptured or infected – personal observation

Lymphoepithelioma-like carcinoma of the skin AD 134:1627–1632, 1998; associated with Epstein-Barr virus infection – ulcerated red nodule of lateral cheek JAAD 62:681–684, 2010 Lymphoma – cutaneous T-cell lymphoma – ulcerated nodule JAAD 82:634–641, 2020; multiple facial nodules AD 145:92–94, 2009; CTCL – ulcerated nodule of temple BJD 156:1379–1381, 2007; primary cutaneous CD4+ small-sized pleomorphic T-cell lymphoma JAMA Derm 149:956–959, 2013; B-cell, T-cell, angiotropic B-cell lymphoma (malignant angioendotheliomatosis), Hodgkin’s disease, immunocytoma (low grade B-cell lymphoma) – reddish-brown papules AD 145:92–94, 2009; JAAD 44:324–329, 2001; primary cutaneous marginal zone B-cell lymphoma (immunocytoma) (MALT) Ped Derm 37:228–229, 2020; JAAD 58:S62–63, 2008; AD 141:1139–1145, 2005; primary cutaneous follicle center B-cell lymphoma JAAD 69:343–354, 2013; plasmacytoid dendritic cell neoplasm (lymphoblastoid natural killer-cell lymphoma) – purple nodule of leg; nodule of face or scalp BJD 162:74–79, 2010; HTLV-1 lymphoma BJD 128:483–492, 1993; Am J Med 84:919–928, 1988; post-transplant lymphoma JAAD 81:600–602, 2019; red-orange papulonodules – HTLV-1 granulomatous T cell lymphoma JAAD 44:525–529, 2001; Hodgkin’s disease AD 116:1038–1040, 1980; follicular CTCL JAAD 48:448–452, 2003; primary cutaneous anaplastic large cell lymphoma BJD 150:1202–1207, 2004; subcutaneous panniculitis-like T-cell lymphoma (with hemophagocytic syndrome) – blue-red nodules of extremities and face; nodules of head and neck, legs, trunk, cheeks, lips Ped Derm 32:526–532, 2015; Ped Derm 23:537–540, 2006; Am J Surg Pathol 15:17–27, 1991; cutaneous Richter syndrome (CLL rapidly developing into large cell lymphoma) Ann DV 122:530–533, 1995; primary cutaneous anaplastic large cell lymphoma – ulcerated purpuric nodule of nasal tip Ped Derm 28:570– 575, 2011; anaplastic large cell lymphoma – umbilicated nodule of cheek Cutis 98:253–256, 2016; cutaneous B-cell lymphoblastic lymphoma JAAD 66:51–57, 2012; primary cutaneous anaplastic large cell lymphoma J Drugs Dermatol 18:460–462, 2019 Lymphomatoid papulosis JAAD 33:741–748, 1995 Malignant cylindrocarcinoma BJD 145:653–656, 2001 Melanocytic nevus Melanoma, including amelanotic melanoma AD 149:413–421, 2013; Semin Oncol 2:5–118, 1975 Merkel cell carcinoma – red or purple nodule SKINmed 12:120–121, 2014; red-pink vascular nodule of face JAAD 65:983–990, 2011; JAAD 49:832–841, 2003; JAAD 43:755–767, 2000; JAAD 36:727– 732, 1997; J Maxillofac Surg 13:39–43, 1985; red nodule of chin Sem Cut Med Surg 30:48–56, 2011; multiple nodules BJD 146:895– 898, 2002; verrucous nodule of cheek Cutis 97:290–295, 2016 Metastases – prostate carcinoma – vascular nodule AD 146:206– 208, 2010

Nodules, Red, Face Mixed tumor (chondroid syringoma) AD 125:1127, 1989 Mucinous carcinoma – multilobulated facial tumor AD 144:1383– 1388, 2008

Granuloma faciale Int J Dermatol 36:548–551, 1997; AD 129:634– 635, 637, 1993

Multiple myeloma AD 139:475–486, 2003

Infantile acne Ped Derm 30:513–518, 2013; cyst Ped Derm 22:166–169, 2005

Neurilemmoma (schwannoma) – pink-gray or yellowish nodules of head and neck

Lichen planus follicularis tumidus – due to anti-PD-1 therapy JAMADerm 155:1197–1198, 2019

Neuroectodermal tumors – congenital primitive neuroectodermal tumors

Malakoplakia Ped Derm 29:541–543, 2012

Neurothekeoma – red nodule of face, nose AD 139:531–536, 2003

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Pyoderma faciale (form of acne rosacea) – sudden onset of nodules, abscesses, sinuses AD 128:1611–1617, 1992

Osteoma – personal observation Pilomatrixoma Ped Derm 26:195–196, 2009 Porocarcinoma AD 136:1409–1414, 2000 Poroid hidradenoma – painful deep red nodule of arm, scalp, face, or trunk AD 146:557–562, 2010 Post-transplant lymphoproliferative disorder – violaceous macules, facial nodules Ped Derm 36:681–685, 2019 Primary cutaneous adenoid cystic carcinoma – violaceous nodules of face and neck JAAD 58:636–641, 2008

SYNDROMES Activated STING in Vascular and Pulmonary syndrome – autoinflammatory disease; butterfly telangiectatic facies; acral violaceous psoriasiform, papulosquamous and atrophic plaques of vasculitis of hands; nodules of face, nose, and ears; fingertip ulcers with necrosis; nail dystrophy; nasal septal perforation; interstitial lung disease with fibrosis; polyarthritis; myositis NEJM 371:507–518, 2014

Progressive nodular histiocytosis – red-brown facial nodules JAMA Derm 149:1229–1230, 2013

Familial histiocytic dermatoarthritis Am J Med 54:793–800, 1973

Rhabdomyomatous mesenchymal hamartoma Am J Dermatopathol 11:58–63, 1989

Hyper IgM syndrome – X-linked; sarcoid-like granulomas; multiple papulonodules of face, buttocks, arms Ped Derm 21:39–43, 2004

Rhabdomyosarcoma AD 124:1687, 1988

Muir-Torre syndrome

Undifferentiated pleomorphic sarcoma – skin colored nodule JAAD 79:853—859, 2018

Neurofibromatosis types I and II – plexiform Schwannoma Ped Derm 29:536–538, 2012

Sebaceous gland carcinoma – ulcerated brown nodule of lateral eyebrow Ped Derm 24:501–504, 2007; cystic sebaceous carcinoma - multilobulated nodule of nose J Drugs Dermatol 6:540–543, 2007

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy JAAD 56:302–316, 2007; Arch Pathol 87:63–70, 1969

Spindle cell liposarcoma BJD 163:638–640, 2010

Xeroderma pigmentosum – multiple cancers JAAD 75:855–870, 2016

Spitz nevus – ulcerated nodule of face Ped Derm 32:148–150, 2015 Squamous cell carcinoma – squamous cell carcinoma, metastatic, of face due to long-term voriconazole therapy – multiple facial ulcerated nodules Clin Inf Dis 58:839, 901–902, 2014

Hereditary progressive mucinous histiocytosis

Sea-blue histiocyte syndrome – nodular facial lesions; brown hyperpigmentation of face JAAD 56:302–316, 2007

TRAUMA

Verrucous carcinoma – hyperkeratotic nodule of cheek BJD 165:694–696, 2011

Cold panniculitis (Haxthausen’s disease) Burns Incl Therm Inj 14:51–52, 1988; AD 94:720–721, 1966; BJD 53:83–89, 1941; popsicle panniculitis Ped Derm 25:502–503, 2008; Pediatr Emerg Care 8:91–93, 1992

Warty dyskeratoma – face, neck, scalp, axillae

Hematoma – personal observation

Trichoepithelioma

Islamic prayer nodule – personal observation

PARANEOPLASTIC DISORDERS Necrobiotic xanthogranuloma with paraproteinemia J Cutan Pathol 27:374–378, 2000; Medicine (Baltimore) 65:376–388, 1986

VASCULAR DISORDERS Arteriovenous malformation – personal observation

Neutrophilic panniculitis associated with myelodysplastic syndrome JAAD 50:280–285, 2004

Angiofibroma

PRIMARY CUTANEOUS DISEASES

Blue rubber bleb nevus syndrome – personal observation

Acne rosacea – pediatric granulomatous rosacea Ped Derm 30:109–111, 2013 Acne vulgaris – inflammatory nodulocystic lesion Alopecia mucinosa – personal observation Darier’s disease – comedonal Darier’s disease; nodules, cysts, ice pick scars BJD 162:687–689, 2010 Erythema elevatum diutinum – violaceous nodules of face JAMADerm 152:331–332, 2016

Benign (reactive) angioendotheliomatosis – red-brown to violaceous nodules or plaques JAAD 38:143–175, 1998 Diffuse neonatal hemangiomatosis – personal observation Facial hemangioma – ulcerated nodule JAAD 64:827–832, 2011; JAAD 64:833–838, 2011 Granulomatosis with polyangiitis Juvenile temporal arteritis – forehead nodule JAAD 62:308–314, 2010 Kimura’s disease – periauricular red nodule JAAD 38:143–175, 1998 Lymphatic malformation – giant tumor of cheek JAAD 70:1050– 1057, 2014

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Phakomatosis pigmentokeratotica – multilobulated pink nodules representing connective tissue nevus Ped Derm 25:76–80, 2008

Fusarium – red nodule with central pallor

Polyarteritis nodosa – in children; fever, peripheral gangrene, black necrosis, livedo reticularis, ulcers, nodules, vesiculobullous lesions, arthralgia, nodules of face and extremities, conjunctivitis JAAD 53:724–728, 2005; Ann Rheum Dis 54:134–136, 1995

Insect bite

Pyogenic granuloma Tufted angioma

NODULES, RED, HAND  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION IgG-4 related skin disease BJD 171:959–967, 2014 Pemphigoid nodularis BJD 142:143–147, 2000 Rheumatoid arthritis – neutrophilic dermatosis J Dermatol 27:782– 787, 2000; rheumatoid nodules Clin Dermatol 38:3041–3048, 2019 Systemic lupus erythematosus – vasculitis Rev Bras Rheumatol Engl Ed 57:583–589, 2017

Gram negative sepsis – personal observation Leishmaniasis – chancre (ulcerated nodule) JAAD 60:897–925, 2009; necrotic red nodule of dorsum of hand BJD 160:311–318, 2009 Leprosy – lepromatous leprosy including erythema nodosum leprosum (vasculitis), subcutaneous lepromas JAMADerm 153:313–314, 2017; J Eur Acad DV 20:344–345, 2006; histoid leprosy Biomedica 35:165–170, 2015 Lyme borreliosis (Borrelia burgdorferi) – acrodermatitis chronica atrophicans – red to blue nodules or plaques; tissue-paper-like wrinkling; pigmented; poikilodermatous; hands, feet, elbows, knees BJD 121:263–269, 1989: Int J Derm 18:595–601, 1979 Milker’s nodule – parapoxvirus species endemic to cattle; starts as flat red papule on fingers or face, progresses to red-blue tender nodule, which crusts; zone of erythema; may resemble pyogenic granulomas JAAD 49:910–911, 2003; AD 111:1307–1311, 1975 Mycetoma JAAD 53:931–951, 2005 Mycobacterium chelonae J Clin Inf Dis 23:1189–1191, 1996 Mycobacterium gordonae Int J Dermatol 26:181–184, 1987 Mycobacterium haemophilum JAAD 59:139–142, 2008

DRUG-INDUCED Imatinib-associated Sweet’s syndrome AD 141:368–370, 2005 Lenalidomide-associated Sweet’s syndrome AD 142:1070–1071, 2006 Neutrophilic eccrine hidradenitis – chemotherapy-induced JAAD 40:367–398, 1999 Sorafenib – interstitial granulomatous dermatitis; red papules, nodules, and plaques of palms AD 147:1118–1119, 2011

Mycobacterium marinum Dermatol Online J Feb 15, 2019, march 15, 2019; Microbiol Spectr April 5, 2017 doi:https://doi.org/10.1128/ microbiolspec.TNM17-0038-2016; Clin Inf Dis 31:439–443, 2000 Mycobacterium tuberculosis Int J Mycobacteriol 8:205–207, 2019 Nocardia asteroides – after a cat scratch BJD 145:684–685, 2001; N. yamanashiensis Tumor 99:e156–158, 2013 Orf – parapoxvirus endemic to sheep and goats Acta DV Croat 27:280–281, 2019; Am Fam Physician 86:77–78, 2012; Transpl Infect 23:e62–64, 2010; JAAD 1172–1174, 1984 Osteomyelitis

EXOGENOUS AGENTS Barber’s sinus J Hand Surg AM 15:652–655, 1991 Calcium hydroxyapatite Aesthet Surg 38:S24–28, 2018 Foreign body granuloma

Phaeohyphomycotic cyst (Exophiala jeanselmei) JAAD 12:207–212, 1985; Phialophora, Cladosporium, and Alternaria JAAD 8:1–16, 1983; E. oligosperma Med Mycol 54:297–301, 2013; Alternaria rosae Transpl Infect Dis June 2017 19(3):doi:https://doi.org/10.1111/ tid.12698

Halogenoderma

Protothecosis – sporangia with cartwheel-like appearance JAAD Case Rep 5:846–848, 2019

Mercury granuloma JAAD 43:81–90, 2000

Pseudomonas hot tub folliculitis – palmoplantar red nodules

Milker’s sinus – tender nodules with discharging sinuses

Rocky Mountain spotted fever – palmoplantar red nodules

Paraffinoma – grease gun injury; nodule, plaque, sinus of hand BJD 115:379–381, 1986

Sealpox (parapoxvirus) – gray concentric nodule with superimposed bulla on dorsum of hand BJD 152:791–793, 2005

Silicone granulomas of face and hands – personal observation

Sporotrichosis – primary chancre Cutis 54:279–286, 1994; Dermatologica 172:203–213, 1986

INFECTIONS AND INFESTATIONS Abscesses Anthrax Bacillary angiomatosis Acta DV Croat 22:294–297, 2014; Ann Plast Surg 70:652–653,; J Hand Surg AM 21:307–308, 1996 Bacterial sepsis – septic emboli – palmoplantar red nodule Chancriform pyoderma Chromomycosis – red papules on dorsum of hand (Chaetomium funicola) Mycopathologica 180:123–129, 2015; BJD 157:1025– 1029, 2007 Cryptococcosis Infection 42:771–774, 2014 Dirofilaria – hand nodule Cutis 72:269–272, 2003

Staphylococcus aureus – abscess (furuncle) Streptococcal suppurative panniculitis – personal observation Subacute bacterial endocarditis – Janeway lesion Med News 75:257–262, 1899; Osler’s node Korean J Intern Med 33:1034– 1035, 2018 Syphilis – primary (chancre), nodular secondary JAAD 82:1–14, 2020; Dermatologica Sinica 36:36–41, 2018; BMJ Case Rep 2013:bcr2013009130.doi:https://doi.org/10.1136/bcr-2013-009130; BJD 115:495–496, 1986, tertiary (gumma) – palmoplantar red nodules Trichophyton rubrum – invasive tinea corporis – personal observation; Majocchi’s granuloma Tanapox – red nodule with headache and backache Bull WHO 63:1027–1035, 1985

Nodules, Red, Hand

INFILTRATIVE DISEASES Acral histiocytic nodules Clin Exp Dermatol 37:245–248, 2012 Langerhans cell histiocytosis resembling cherry angiomas Ped Derm 3:304–310, 1986 Mastocytoma – palmar nodule Ped Derm 15:386–387, 1998 Myxoid cyst G Ital DV 153:847–854, 2018 Self-healing juvenile cutaneous mucinosis – red nodules of face, scalp, hand; macrodactyly (enlarged thumbs); periarticular papules and nodules, painful polyarthritis; linear ivory white papules, multiple subcutaneous nodules, indurated edema of periorbital and zygomatic areas JAAD 55:1036–1043, 2006; AD 131:459–461, 1995; Ann DV 107:51–57, 1980; Lyon Med 230:470–474, 1973

INFLAMMATORY DISEASES Erythema elevatum diutinum J Hand Surg Am 44:522ei-522e5, 2019; Cutis 34:41–43, 1984; palmoplantar nodules BJD 142:116– 119, 2000

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Chondroma – solitary chondroma of skin Dermatol Online J 19:18176 may 15, 2013 Clear cell acanthoma JAAD 14:918–927, 1986 Dermatofibrosarcoma protuberans Eccrine porocarcinoma JAAD 35:860–864, 1996 Eccrine poroma AD 74:511–512, 1956 Eccrine spiradenoma Eccrine syringofibroadenoma Epithelioid sarcoma Hautarzt 63:278–282, 2012 Fibrosarcoma Fibrous hamartoma of infancy – nodules of hands and feet J Hand Surg 22A:740–742, 1997 Giant cell tumor of the tendon sheath Case Rep Orthop 2016:1834740:doi.https://doi.org/10.1155/2016/1834940; J Clin Diagn Res 8:170–171, 2014 Granular cell tumor Indian Dermatol Online J 4:33–36, 2013 Kaposi’s sarcoma – classic type JAAD 38:143–175, 1998; Int J Dermatol 36:735–740, 1997; Dermatology 190:324–326, 1995

Erythema multiforme – palmoplantar red nodules

Keratoacanthoma

Erythema nodosum – palmoplantar red nodules J Dermatol 27:420–421, 2000

Leiomyosarcoma

Panniculitis – palmoplantar red nodule

Lymphoma – B-cell, T-cell, angiotropic B cell lymphoma (malignant angioendotheliomatosis), Hodgkin’s disease, immunocytoma (low grade B cell lymphoma) – reddish-brown papules JAAD 44:324– 329, 2001; HTLV-1 lymphoma BJD 128:483–492, 1993; Am J Med 84:919–928, 1988; red-orange papulonodules – HTLV-1 granulomatous T cell lymphoma JAAD 44:525–529, 2001; pityriasis lichenoides-like CTCL BJD 142:347–352, 2000

Pseudosarcomatous nodular fasciitis

Lymphomatoid papulosis

Pyoderma gangrenosum Arch Bone Jt Surg 4:83–86, 2016

Malignant eccrine poroma

Relapsing eosinophilic perimyositis – fever, fatigue, and episodic muscle swelling; erythema over swollen muscles BJD 133:109–114, 1995

Malignant fibrous histiocytoma

Fibroblastic rheumatism JAAD 66:959–965, 2012 Idiopathic palmoplantar hidradenitis of children AD 131:817–820, 1995; J Cut Path 21:289–296, 1994; palmar eccrine hidradenitis Ped Derm 34:e283–285, 2017

Sarcoid

Melanoma, including amelanotic melanoma Semin Oncol 2:5–118, 1975; acral lentiginous melanoma Clin Exp Dermatol 36:174–177, 2011

METABOLIC DISEASES

Merkel cell tumor JAAD Case Rep 4:507–508, 2018; Hand (NY)11:Np24–29, 2016; JAAD 58:375–381, 2008; AD 123:1368– 1370, 1987

Calcinosis cutis – tumoral calcinosis Cryoproteinemia – reactive angiomatosis with cryoproteinemia JAAD 27:969–973, 1992 Gout – tophi Indian J Med Res 149:682–683, 2019; BMJ Case Rep Oct 28, 2018 Low IL-2 level JAAD 29:473–477, 1993

NEOPLASTIC DISORDERS

Metaplastic synovial cyst Iran Red Crescent Med J 17:e22467. doi:https://doi.org/10.5812/ircmj.22467 Metastatic carcinoma – thyroid, renal cell or GI tract, prostate AD 128:1533–1538, 1992; breast Indian J DV Lerol 77:695–698, 2011; hepatocellular carcinoma Hand Surg 17:131–134, 2012 Myelofibrosis – extramedullary hematopoiesis in myelofibrosis AD 112:1302–1303, 1976 Myxoid neurothekeoma Niger J Surg 19:32–34, 2013 Nodular hidradenoma Cutis 95:E1–3, 2015

Acquired digital fibrokeratoma Int J Dermatol 58:151–158, 2019

Ossifying plexiform tumor J Cutan Pathol 42:61–65, 2015

Aggressive digital papillary adenocarcinoma – exophytic friable multilobulated tumor arising from sweat glands Dermatol Online J April 15, 2018; JAAD 60:331–339, 2009

Osteochondroma

Angioleiomyoma Cureus 12:e7530, 2020

Sarcomatoid carcinoma Clin Exp Dermatol 37:505–508, 2012

Angiomatoid malignant fibrous histiocytoma AD 121:275–276, 1985

Schwannomas Medicine (Balt)98:e14605, 2019

Angiosarcoma

Sebaceous adenoma in AIDS AD 124:489–490, 1988

Apocrine nevus Juvenile aponeurotic palmoplantar fibroma

Spitz nevi mimicking pyogenic granulomas in black children JAAD 23:842–845, 1990

Basal cell carcinoma

Squamous cell carcinoma

Bony exostosis Dermatol Online J 10:15 July 15, 2004

Superficial acral fibromyxoma Int J Dermatol 54:499–508, 2015

Chloroma

Sweat gland tumor

Chondroid syringoma Pathol Res Pract 198:755–764, 2002

Verrucous carcinoma

Plantar and palmar fibromatosis J Dtsch Dermatol Ges 17:393–397, 2019

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PRIMARY CUTANEOUS DISEASES Angiolymphoid hyperplasia with eosinophilia J Med Case Rep 13:87, March 27, 2019; Int J Surg Case Rep 39:84–87, 2017 Granuloma annulare – perforating granuloma annulare – palmoplantar red nodule JAAD 32:126–127, 1995; subcutaneous granuloma annulare Acta DV Croat 25:292–294, 2017; Seminar Cut Med Surg 26:96–99, 2007; “pseudorheumatoid nodules” Am J Dermatopathol 27:1–5, 2005 Granuloma faciale – extrafacial granuloma faciale

SYNDROMES

Intravascular papillary endothelial hyperplasia Skeletal Radiol 45:235–242, 2016; Cutis 59:148, 1997; JAAD 10:110–113, 1984; vascular nodule of palmar third finger BJD 166:1147–1149, 2012 Kaposi’s sarcoma including Kaposi’s sarcoma in Castleman’s disease JAAD 26:105–109, 1992 Polyarteritis nodosa Pustular vasculitis of the hands (neutrophilic dermatosis of the dorsal hands AD 138:361–365, 2002; JAAD 32:192–198, 1995 Pyogenic granuloma JAAPA 31:27–29, 2018; J Eur Acad DV 31:e512–513m 2017 Self-healing pseudoangiosarcoma AD 124:695–698, 1988 Targetoid hemosiderotic hemangioma JAAD 19:550–558, 1988

Acral dysesthesia syndrome

Tufted angioma, acquired Int J Dermatol 57:e54–55, 2018

Behcet’s syndrome J Rheumatol 25:2469–2472, 1998

Vasculitis

Bowel bypass syndrome Blue rubber bleb nevus syndrome – phlebectasias Ped Derm 3:75–78, 1985 Fibroblastic rheumatism J Dermatol 45:e1142–1143, 2018

 ODULES, RED OR VIOLACEOUS, N VASCULAR APPEARANCE

Maffucci’s syndrome Actas Dermsifiliogr 108:861–862, 2017 Multicentric reticulohistiocytosis J Hand Surg Am 45:457.e1–457. e5, 2020; Rheumatol (Oxford) Nov 19, 2019

 UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION

POEMS syndrome (glomeruloid hemangioma) JAAD 21:1061– 1068, 1989; JAAD 12:961–964, 1985

Dermatomyositis – presenting as panniculitis JAAD 23:127–128, 1990

Pseudo-Kaposi’s sarcoma in reflex sympathetic dystrophy JAAD 22:513–520, 1990 Relapsing eosinophilic perimyositis – fever, fatigue, and episodic muscle swelling; erythema over swollen muscles BJD 133:109–114, 1995 RS3PE – remitting seronegative synovitis with pitting edema BMJ Case Rep April 22, 2020 Sweet’s syndrome JAAD 31:535–536, 1994 including drug-induced Sweet’s syndrome – all-trans retinoic acid, furosemide JAAD 21:339–343, 1989; G-CSF, GM-CSF, hydralazine, minocycline, trimethoprim-­sulfamethoxazole, triphasil

TRAUMA Delayed pressure urticaria – palmoplantar red nodules

Graft vs. host disease, chronic – chronic sclerotic graft vs. host disease-associated angiomatosis (eruptive violaceous vascular nodules) BJD 174:782–784, 2016; JAAD 71:745–753, 2014; BJD 149:667–668, 2003; JAAD 10:918–921, 1984   Differential diagnosis:  Reactive angioendotheliomatosis – brown to violaceous ulcerated patches and plaques  Diffuse dermal angiomatosis – brown to violaceous ulcerated patches and plaques over legs, pannus, or breast associated with obesity  Acroangiomatosis   Atypical vascular lesions following breast radiation   Pyogenic granuloma   Cavernous hemangioma   Tufted angioma – deep red to violaceous plaque or nodule

Perniosis (chilblains)

Low interleukin 2 level – vascular nodules and plaques JAAD 29:473–477, 1993

Vibratory angioedema – palmoplantar red nodules

Lupus erythematosus – lupus profundus JAAD 14:910–914, 1986

VASCULAR DISORDERS Acral pseudolymphomatous angiokeratoma of children (APACHE) BJD 124:387–388, 1991; AD 126:1524–1525, 1990 Acroangiodermatitis (pseudo-Kaposi’s sarcoma) after A-V shunt JAAD 21:499–505, 1989; Arch Derm Res 281:35- 39, 1989 Angiokeratoma Cholesterol emboli – palmoplantar red nodules Disseminated neonatal hemangiomatosis JAAD 24:816–818, 1991; Ped Derm 8:140–146, 1991 Eruptive pseudoangiomatosis JAAD 29:857–859, 1993 Glomus tumor J med Case Rep 12:302, Oct 18, 2018; Mol Clin Oncol 2:237–239, 2014; Ann Plast Surg 43:436–438, 1999 Granulomatosis with polyangiitis Immun Infekt 18:89–90, 1990 Hemangioma Skeletal Radiol 39:1097–1102, 2010 Hemangiopericytoma

Pemphigoid nodularis (purple) AD 126:1522–1523, 1990; JAAD 21:1099–1104, 1989; nonbullous pemphigoid JAAD 29:293, 1993 Pemphigus vulgaris JAAD 23:522–523, 1990 Rheumatoid nodule

CONGENITAL LESIONS Benign and/or disseminated (diffuse) neonatal hemangiomatosis – diffuse (visceral involvement) or benign (only cutaneous involvement) Ped Derm 21:469–472, 2004; JAAD 37:887–920, 1997; JAAD 24:816–818, 1991; Ped Derm 8:140–146, 1991 Congenital infantile fibrosarcoma – ulcerated vascular nodule Cutis 89:61–64, 2012 Encephalocele Soc Ped Derm Annual Meeting, 2005 Epulis 10850508 Hamartoma with ectopic meningothelial elements – simulates angiosarcoma Am J Surg Pathol 14:1–11, 1990

Nodules, Red or Violaceous, Vascular Appearance

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Hemangiomatous branchial clefts, lip pseudoclefts, unusual facies – hemangiomatous branchial clefts in retroauricular areas extending down along the sternocleidomastoid muscle Am J Med Genet 14:135–138, 1983

Foreign body granuloma – silk or polymer sutures, talc, starch, oily material, silicone, hair, silica, tattoo, zirconium, beryllium, wood splinter

Meningocele – sequestrated meningocele Ped Derm 14:315–318, 1994

Silicone granuloma AD 130:787–792, 1994

Mercury granuloma JAAD 12:296–303, 1985

Nasal glioma Neonatal purple tumors or plaques – RICH, fibrosarcoma, malignant hemangiopericytoma, dermatofibrosarcoma protuberans Ped Derm 19:5–11, 2002 Omphalomesenteric duct remnants (vitelline duct remnant) – completely patent, peripheral portion – cherry red nodule; combined omphalomesenteric and urachal remnants differential diagnosis includes pyogenic granuloma (umbilical granuloma), sarcomas, congenital hemangiomas, patent urachus (passage of urine through umbilicus), ligated umbilical hernia Ped Derm 24:65–68, 2007; Cutis 76:224, 233–235, 2005 Patent vitello-intestinal duct (persistent urachal fistula) – vascular nodule of umbilicus of infancy AD 145:1447–1452, 2009 Pyogenic granulomas, congenital disseminated Ped Derm 26:323– 327, 2009 Sacrococcygeal teratoma – masquerading as infantile hemangioma; red vascular plaque; red subcutaneous nodule of medial buttock Ped Derm 30:112–116, 2013 Spinal dysraphism with overlying protrusion, dimple, sinus, lipoma, faun tail nevus, dermoid cyst, hemangioma, port wine stain AD 114:573–577, 1978; AD 112:1724–1728, 1976 Thyroglossal duct cyst Umbilical granuloma – vascular nodule Ped Derm 36:393–394, 2019; congenital Ped Derm 28:404–407, 2011 Urachus – complete or partial patency of urachus

INFECTIONS AND INFESTATIONS Alternariosis Amebiasis, including Acanthamoeba in AIDS JAAD 26:352–355, 1992 Aspergillosis, primary cutaneous – purple or brown AD 129:1189– 1194, 1993; AD 124:121–126, 1988 Bacillary angiomatosis (Bartonella henselae) Clin Inf Dis 33:772– 779, 2001; BJD 136:60–65, 1997; J Hand Surg (Am) 21:307–308, 1996; JAMA 269:770–775, 1993; Hautarzt 44:361–364, 1993; JAAD 24:802–803, 807–808, 1991; JAAD 22:501–512, 1990; vascular papules or nodules on gingival, palate or floor of mouth J Oral Pathol 22:235–239, 1993 Bartonellosis – Bartonella bacilliformis; bacillary angiomatosis; Andes mountains, Peru, Colombia, Ecuador; Oroya fever with verruga peruana; sandflies and fleas as vectors; red papules in crops become nodular, hemangiomatous or pedunculated; face, neck, extremities, mucosal lesions; 1–-4 mm pruritic red papules; massive hemolytic anemia, high fever, muscle pain, delirium, coma JAAD 59:179–1206, 2008; JAAD 54:559–578, 2006; Clin Inf Dis 33:772–779, 2001; Ann Rev Microbiol 35:325–338, 1981; 22:501– 512, 1990 Bipolaris spicifera (dematiaceous fungus) Botryomycosis JAAD 21:1312–1314, 1989; intraoral botryomycosis 10530188 Brucellosis – erythema nodosum-like AD 125:380–383, 1989

DRUG-INDUCED Capecitabine – pyogenic granuloma-like paronychial lesions BJD 147:1270–1272, 2002 Cyclosporine-induced T cell infiltrates 5-fluorouracil, capecitabine, tegafur – pyogenic granulomas JAAD 71:203–214, 2014 Furosemide-induced Sweet’s eruption JAAD 21:339–343, 1989 Gefitinib (epidermal growth factor receptor inhibitor) – pyogenic granulomas of proximal nail folds AD 142:939, 2006 Indinavir (protease inhibitor)-induced paronychial pyogenic granuloma JAAD 46:284–293, 2002; BJD 140:1165–1168, 1999; NEJM 338:1776–1777, 1998 Lisinopril – associated with development of Kaposi’s sarcoma BJD 147:1042–1044, 2002

Candida – sepsis, chronic mucocutaneous candidiasis Cat scratch disease JAAD 31:535–536, 1994 Cave tick (Ornithodoros tholozani) bite JAAD 27:1025–1026, 1992 Chancriform pyoderma Chromomycosis AD 123:519–524, 1987 Co-existent infections of Kaposi’s sarcoma in HIV disease – cytomegalovirus, molluscum contagiosum, Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, Mycobacterium avium-intracellulare, Mycobacterium tuberculosis Clin Inf Dis 58:540,596–597, 2014; Pathol Res Int 2011:398546; Am J Dermatopathol 34:e7–9, 2012; JAAD 62:676–680, 2010 Cryptococcosis JAAD 26:122–124, 1992; cryptococcosis and Kaposi’s sarcoma, coexistent – giant purple tumor of lower face in HIV disease; satellite papules Clin Inf Dis 58:540,596–597, 2014 Cytomegalovirus JAAD 18:1333–1338, 1988

Neuroleptics – pseudolymphoma AD 128:121–123, 1992

Dental sinus

Retinoids, systemic – pyogenic granulomas

Dirofilariasis

Sulindac – pancreatitis and subcutaneous fat necrosis JAAD 13:366–369, 1985

Echovirus infection – eruptive pseudoangiomatosis JAAD 29:857– 859, 1993; vascular papules or nodules; Echovirus 25, 32; Coxsackie B virus Ped Derm 19:76–77, 2002

Vemurafenib – pyogenic granuloma NEJM 371:1265–1267, 2014

Furunculosis – Staphylococcus aureus

EXOGENOUS AGENTS Aspartame-induced lobular panniculitis JAAD 24:298–300, 1991 Duoderm-induced exuberant granulation tissue

Fusarium Glanders Gnathostomiasis JAAD 13:835–836, 1985 Histoplasmosis JAAD 29:311–313, 1993, JAAD 23:422–428, 1990; histoplasma panniculitis AD 121:914–916, 1985

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Insect bites, including exaggerated insect bite reaction in AIDS JAAD 29:269–272, 1993 Leishmaniasis – AIDS-related visceral leishmaniasis BJD 143:1316–1318, 2000; diffuse cutaneous leishmaniasis; mucocutaneous leishmaniasis J Emerg Med 20:353–356, 2001; AD 134:193– 198, 1998; J Clin Inf Dis 22:1–13, 1996 Leprosy, including erythema nodosum leprosum JAAD 14:59–69, 1986 Lyme disease AD 120:1520–1521, 1984 Lymphogranuloma venereum Malacoplakia due to Escherichia coli Meningococcus Milker’s nodule – starts as flat red papule on fingers or face, progresses to red-blue tender nodule, which crusts; zone of erythema; may resemble pyogenic granulomas AD 111:1307–1311, 1975 Mucormycosis Mycetoma Mycobacterium avium-intracellulare Mycobacterium chelonae JAAD 28:352–355, 1993

Sporotrichosis – primary chancre Syphilis – primary (chancre), extragenital chancre, nodular and nodulo-ulcerative secondary AD 113:1027–1032, 1997; tertiary (gumma) Tick bite granuloma Toxoplasmosis JAAD 14:600–605, 1986 Trichophyton rubrum, invasive JAAD 51:s101–104, 2004; Cutis 67:457–462, 2001; Majocchi’s granuloma Trichosporon beigelii Trypanosomiasis – primary lesion Tularemia Tungiasis Typhoid fever Verruca vulgaris Xanthomonas maltophilia Yaws – “crab yaws” – raspberry like; primary red papule, ulcerates, crusted; satellite papules; become round ulcers, papillomatous or vegetative friable nodules which bleed easily (framboesia) Zygomycosis

Mycobacterium fortuitum Mycobacterium haemophilum Mycobacterium intracellulare (erythema nodosum-like nodule) JAAD 27:1019–1021, 1992 Mycobacterium kansasii Mycobacterium malmoense Mycobacterium marinum Mycobacterium tuberculosis – acute miliary, erythema induratum, lupus vulgaris Mycobacterium ulcerans Myiasis, cuterebrid myiasis JAAD 763–772, 1989 Nocardiosis AD 130:243–248, 1994; JAAD 26:1132–133, 1992; N. brasiliensis Ped Derm 2:49–51, 1985 North American blastomycosis Onchocercoma Orf – vascular nodule of fingertip with or without ulceration JAMADerm 151:1032–1033, 2015;JAAD 29:256–257, 1993; AD 126:356–358, 1990; JAAD 11:72–74, 1984

INFILTRATIVE DISEASES Primary amyloidosis – in Campbell de Morgan spots; targetoid lesions of amyloid in pre-existent capillary hemangioma BJD 112:209–211, 1985; tumefactive amyloid Cutis 46:255–259, 1990; nodular primary cutaneous amyloidosis JAAD 14:1058–1062, 1986 Angioplasmocellular hyperplasia – red nodule with red rim, ulcerated nodule, vascular nodule of face, scalp, neck, trunk, and leg JAAD 64:542–547, 2011 Jessner’s lymphocytic infiltrate Langerhans cell histiocytosis Ped Derm 26:751–753, 2009; Australas J Dermatol 50:77–97, 2009; Ped Derm 3:75–8, 1985; resembling cherry angiomas Ped Derm 3:75–78, 1985; eosinophilic granuloma; self-healing Langerhans cell histiocytosis Cutis 102:309,316,321, 2018 Xanthoma disseminatum AD 127:1717–1722, 1991; AD 86:582– 589, 1962

Osteomyelitis

INFLAMMATORY DISEASES

Papular urticaria

Adiposis dolorosa

Phaeohyphomycosis AD 123:1346–1350, 1987; phaeohyphomycotic cyst (Exophiala jeanselmei) JAAD 12:207–212, 1985

Crohn’s disease, metastatic (with or without ulceration) AD 126:645–648, 1990; JAAD 19:421–425, 1988

Phialophora repens

Endometriosis – (32% of all umbilical tumors, most common); cutaneous endometrioma – blue-red nodule AD 147:1317–1322, 2011; AD 112:1435–1436, 1976; JAMA 191:167, 1965; duVivier p.686, 2003; AD 135:1113–1118, 1999

Phlegmon (Serratia) Pneumocystis carinii Porto-caval shunt, infected Protothecosis – keratoacanthoma-like AD 121:1066–1069, 1985; purple subcutaneous nodules Cutis 63:185–188, 1999 Pseudomonas sepsis Ped Derm 4:18–20, 1987 Rhinosporidiosis – vascular nodules of nose, extending to pharynx or lips NEJM 380:1359, 2019; Mycopathologica 73:79–82, 1981; Arch Otolaryngol 102:308–312, 1976 Scabies – apple jelly JAAD 32:758–764, 1995 Scolecobasidium constrictum (dematiaceous fungus) Sparganosis

Hidradenitis suppurativa Membranous fat necrosis AD 129:1331–1336, 1993 Neutrophilic eccrine hidradenitis JAAD 28:775–776, 1993; JAAD 26:793–794, 797, 1992; JAAD 11:584–590, 1984 Pilonidal cyst and sinus Pseudolymphomatous folliculitis Pseudosarcomatous nodular fasciitis Cancer 49:1668–1678, 1982 Pyoderma gangrenosum Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy; histiocytic lymphophagocytic panniculitis AD

Nodules, Red or Violaceous, Vascular Appearance 124:1246–1249, 1988, JAAD 18:1322–1332, 1988; Ped Derm 4:247–253, 1987; mimicking pyogenic granuloma Semin Diagn Pathol 7:19–73, 1990 Sarcoid AD 120:1239–1240, 1984

METABOLIC Angiokeratoma corporis diffusum   Adult type neuraminidase deficiency   Fabry’s disease   Fucosidosis type II   Sialidosis type II   Late infantile galactosialidosis   Aspartyl glycosaminuria   Adult onset GM1 gangliosidosis   alpha N-acetyl galactosaminidase deficiency   beta mannosidase deficiency   normal variant

NEOPLASTIC DISEASES Acrospiroma (clear cell, nodular, or solid-cystic hidradenoma) JAAD 21:271–277, 1989 Adenosquamous carcinoma Cutis 94:231–233, 2014 Aggressive digital papillary adenocarcinoma – exophytic friable tumor JAAD 60:331–339, 2009 Alveolar rhabdomyosarcoma Ped Derm 5:254–256, 1988; neonatal tongue lesion with massive macroglossia Soc Ped Derm Annual Meeting, July 2005 Aneurysmal benign fibrous histiocytoma Histopathology 26:323– 331, 1995 Angiokeratoma – personal observation Angiolipoleiomyoma, periungual JAAD 23:1093–1098, 1990; Angioleiomyoma – digital JAAD 29:1043–1044, 1993 Angiomatous nevus; angiomatous nevus following radiation Angiomatoid malignant fibrous histiocytoma AD 121:275–276, 1985

Blueberry muffin baby – widespread blue, purple, or red macules papules or nodules of trunk, head, and neck; may develop petechiae on surface   Dermal erythropoiesis   Congenital infections    Rubella    Cytomegalovirus    Coxsackie B2    Syphilis    Toxoplasmosis   Hereditary spherocytosis   Rh incompatibility    ABO blood-group incompatibility    Twin-twin transfusion syndrome   Neoplastic infiltrates   Congenital leukemia   Neuroblastoma   Congenital rhabdomyosarcoma   Other disorders    Neonatal lupus erythematosus

Angiomyxoma JAAD 33:352–355, 1995

Calcinosis cutis – tumoral calcinosis

Bony exostosis

Congenital disorders of glycosylation (CDG-Ie) – eyelid telangiectasia, hemangiomas, inverted nipples, microcephaly; dolichol-phosphate-mannose synthase Ped Derm 22:457–460, 2005

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Angiosarcoma including Stewart-Treves tumor Cancer 77:2400– 2406, 1996; AD 124:263–268, 1988; angiosarcoma of the face and scalp (Wilson-Jones angiosarcoma) BJD 172:1156–1158, 2015; JAAD 38:143–175, 1998; red-black breast nodules following breast irradiation for breast cancer JAAD 54:499–504, 2006; angiosarcoma in clotted A-V shunt JAAD 65:882–883, 2011 Apocrine adenoma Apocrine nevus JAAD 18:579–581, 1988 Juvenile aponeurotic palmoplantar fibroma Atrial myxoma BJD 115:239–242, 1986 Atypical fibroxanthoma AD 135:1113–1118, 1999; pyogenic granuloma-like lesion AD 146:1399–1404, 2010; AD 112:1155– 1157, 1976; Cancer 31:1541–1542, 1973 Basal cell carcinoma Acta Pathol Microbiol Scand 88A:5–9, 1980 Blastic plasmacytoid dendritic cell neoplasm – purple nodules of back, vascular nodule of trunk; “purple plum” nodule of face JAMADerm 154:492–494, 2018; BJD 169:579–586, 2013 Carcinoid, primary cutaneous JAAD 22:366–370, 1990 Caruncle – vascular papillary growth of urinary meatus JAAD 57:371–392, 2007

Primary umbilical endometriosis – solitary vascular appearing umbilical nodule JAMADerm 156:339–340, 2020   Differential diagnosis includes:   Keloid    Urachal duct cyst    Omphalomesenteric duct remnant   Metastatic adenocarcinoma   Abdominal hernia   Nodular melanoma

Castleman’s disease (giant lymph node hyperplasia) JAAD 29:778–780, 1993

Gamma heavy chain disease JAAD 23:988–991, 1990

Clear cell acanthoma JAAD 16:1075–1078, 1987

Gout – tophi

Clear cell variant of mucoepidermoid carcinoma JAAD 29:642–644, 1993

Primary hyperoxalosis IgA benign monoclonal gammopathy – violaceous nodules JAAD 21:1303–1304, 1989 Nodular pretibial myxedema AD 129:365–370, 1993 Pregnancy – pyogenic granulomas; small hemangiomas Cutis 13:82–86, 1974 Reactive angiomatosis with cryoproteinemia JAAD 27:969–973, 1992

CD4 + CD56+ hematodermic neoplasm – vascular nodule of forehead; red plaques of face; tumor of plasmacytoid dendritic cells Cutis 89:278–283, 2012 Chondroblastoma, subungual – toe tip Ped Derm 21:452–453, 2004 Chondroma, solitary Chondroid syringoma AD 84:835–847, 1961

Cylindroma Cutis 56:239–240, 1995 Dermal dendrocytoma (keratotic) AD 126:689–690, 1990 Dermatofibroma – dermatofibroma with spreading satellitosis JAAD 27:1017–1019, 1992 Dermatofibrosarcoma protuberans – congenital AD 139:207–211, 2003; Pre-AAD Pediatric Derm Meeting, March 2000 Eccrine acrospiroma – purple nodule Cutis 49:49–50, 1992; Ped Derm 6:53–54, 1989

750 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Eccrine angiomatous hamartoma – vascular nodule; macule, red plaque, acral nodule of infants or neonates; painful, red, purple, blue, yellow, brown, skin-colored JAAD 47:429–435, 2002; JAAD 37:523–549, 1997; Ped Derm 13:139–142, 1996 Eccrine poroma Cutis 54:183–184, 1994 Eccrine spiradenoma Int J Dermatol 37:221–223, 1998; J Cut Pathol 10:312–320, 1983 Eccrine sweat gland carcinoma AD 122:585–590, 1986; metastatic eccrine gland carcinoma Eccrine syringofibroadenoma AD 126:945–949, 1990 Embryonal rhabdomyosarcoma Ped Derm 22:218–221, 2005 Endometriosis – brown JAAD 21:155, 1989 Epidermoid inclusion cyst – ruptured or with hemorrhage Epithelioid cell histiocytoma BJD 120:185–195, 1989 Epithelioid sarcoma JAAD 26:302–305, 1992

Lymphocytoma cutis Lymphoma – cutaneous T-cell lymphoma, immunoblastoma, lymphoplasmacytic lymphoma JAAD 16:1106–110,1987; HTLV-1 lymphoma, Ki-1+, CD 8+ lymphoepithelioid lymphoma JAAD 29:871–875, 1993; cytophagic panniculitis (B-cell lymphoma) JAAD 13:882–885, 1985; primary cutaneous anaplastic large cell lymphoma – vascular nodules or plaques JAAD 70:724–735, 2014; BJD 150:1202–1207, 2004; large cell lymphoma resembling sarcoid JAAD 28:327–330, 1993; CD 30+ anaplastic large cell lymphoma Ped Derm 21:525–533, 2004; AD 139:1075–1080, 2003; primary cutaneous CD30+ lymphoproliferative disorder (CD8+/CD4+) JAAD 51:304–308, 2004; primary cutaneous anaplastic large cell lymphoma JAAD 74:1135–1143, 2016; plasmablastic lymphoma after transplant BJD 149:889–890, 2003; primary cutaneous follicle center B-cell lymphoma BJD 157:1205–1211, 2007 Lymphomatoid granulomatosis (angiocentric lymphoma) AD 127:1693–1698, 1991

Erythema nodosum with B cell lymphoma infiltrate JAAD 32:361– 363, 1995

Lymphomatoid papulosis

Extramedullary hematopoiesis in chronic idiopathic myelofibrosis with myelodysplasia JAAD 55:S28–31, 2006

Malignant fibrous histiocytoma resembling mycetoma – vascular nodule of leg Sem Cut Med Surg 21:159–165, 2002; purple JAAD 29:318–321, 1993

Fibroma Fibrosarcoma/spindle cell sarcoma – red or violaceous nodule; fibrosarcoma, neonatal – ulcerated vascular nodule Ped Derm 25:141–143, 2008; Ped Derm 23:330–334, 2006; Soc Ped Derm Annual Meeting, July 2005; JAAD 50:S23–25, 2004 Giant cell tumor of the tendon sheath (finger nodules) Cancer 57:875–884, 1986 Glomangiosarcoma 18521375 Glomus tumor – single or multiple; malignant glomus tumor Derm Surg 27:837–840, 2001 Granular cell myoblastoma – benign or malignant AD 126:1051– 1056, 1990; AD 130:913–918, 1994 Hemophagocytic syndrome – purple nodule JAAD 25:919–924, 1991; AD 128:193–200, 1992 Hibernoma – neck, axilla, central back; vascular dilatation overlying lesion AD 73:149–157, 1956 Indeterminate cell tumor JAAD 15:591–597, 1986 Infantile choriocarcinoma JAAD 14:918–927, 1986 Infantile myofibromatosis – resembling hemangioma JAAD 71:264–270, 2014; Ped Derm 27:29–33, 2010; JAAD 41:508, 1999; red nodule Curr Prob Derm 14:41–70, 2002; Ped Derm 18:305–307, 2001; Ped Derm 8:306–309, 1991 Inverted follicular keratosis 11411260 Juvenile xanthogranuloma JAAD 29:868–870, 1993 Kaposi’s sarcoma Dermatol Clin 24:509–520, 2006; Cutis 54:275– 260, 1994; of the nasal mucosa J Laryngol Otol 112:280–282, 1998; in Castleman’s disease JAAD 26:105–109, 1992; violaceous eyelid papules and pulmonary infiltrates in HIV disease with immune reconstitution syndrome NEJM 369;1152–1161, 2013; Keratoacanthoma Leiomyomas Leiomyosarcoma Ped Derm 14:281–283, 1997 Leukemia cutis JAAD 11:121–128, 1984; granulocytic sarcoma AD 120:1341–1343, 1984; congenital leukemia cutis AD 129:1301– 1306, 1993 Lipoblastoma – mimicking hemangioma Pediatrics 105:123–128, 2000; Ped Derm 16:77–83, 1999; ulcerated vascular nodule Ped Derm 34:180–186, 2017

Malignant eccrine poroma

Malignant histiocytosis Malignant rhabdoid tumor Ped Derm 13:468–471, 1997 Malignant synovioma Mammary duct ectasia – bloody nipple discharge of infancy with hemorrhagic nodule Ped Derm 34:361–362, 2017; AD 145:1068– 1069, 2009   Differential diagnosis includes:   Cystic mastitis   Epithelial hyperplasia   Intraductal carcinoma   Intraductal papilloma   Hemangioma Melanocytic nevi – giant congenital melanocytic nevi with proliferative nodules AD 140:83–88, 2004; irritated nevus Melanoma – primary cutaneous BJD 172:662–668, 2015; NEJM 368:1536, 2013; Ped Derm 27:201–203, 2010; giant vascular tumor JAMADerm 150:574–575, 2014; bright red vascular nodule of helix JAMADerm 151:105–106, 2015; primary dermal melanoma JAAD 75:1263–1265, 2016; melanotic melanoma Semin Oncol 2:5–118, 1975; amelanotic subungual melanoma mimicking pyogenic granuloma J R Coll surg Edinb 47:638–640, 2002; amelanotic acral lentiginous melanoma BJD 155:561–569, 2006; metastatic melanoma Cutis 69:353–356, 2002; amelanotic acral melanoma – red plaque of toe tip JAAD 69:700–707, 2013; spindle cell amelanotic melanoma BJD 155:81–88, 2006; amelanotic melanoma arising in large congenital melanocytic nevus – multilobulated vascular nodule JAAD 68:913–925, 2013 Merkel cell tumor BJD 174:158–164, 2016; AD 140:609–614, 2004; JAAD 31:271–272, 1994; AD 127:571–576, 1991; AD 123:1368– 1370, 1987; cherry red nodules with shiny surface J Drugs in Dermatol 9:779–784, 2010; BJD 169:294–297, 2013; red-pink vascular nodule of face JAAD 65:983–990, 2011; mimicking angiosarcoma; eyelid papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.101; purple plum Metastases – renal cell (purple) (red vascular) Cutis 101:78, 117–118, 2018; Cutis 98:376,383–384, 2016; Derm Surg 27:192– 194, 2001; vascular red papule of nipple (renal cell carcinoma) Cutis 90:196–199, 2012; Cutis 86:69, 73–74, 2010; oat cell carcinoma, anaplastic carcinoma, carcinoid, GI tract, retinoblas-

Nodules, Red or Violaceous, Vascular Appearance toma, Ewing’s sarcoma, neuroblastoma, and leukemia cutis, thyroid, bronchogenic carcinoma AD 126:665–670, 1990; others AD 127:571, 1991; prostate AD 146:206–208, 2010; AD 128:1533– 1538, 1992; J Urol 113:734–735, 1975; testicular choriocarcinoma Cutis 67:117–120, 2001; Sister Mary Joseph nodule (umbilical metastatic carcinoma) JAAD 10:610–615, 1984; colon Cutis 80:469–472, 2007; bladder carcinoma AD 145:213–215, 2009; endometrial carcinoma; metastatic serous adenocarcinoma of the ovary – peristomal red nodule JAMA 319:1158–1159, 2018; serous papillary carcinoma JAMADerm 155:956, 2019; metastatic endometrial carcinoma Cutis 103:217–218, 2019

Rhabdomyomatous mesenchymal hamartoma – red vascular polypoid mass of labia majora Ped Derm 26:753–755, 2009;

Multinucleate cell angiohistiocytoma Cutis 59:190–192, 1997

Sebaceous gland carcinoma – ulcerated violaceous nodule BJD 166:222–224, 2012; JAAD 61:549–560, 2009; Dermatol Ther 21:459–466, 2008; AD 137:1367–1372, 2001; Nippon Ganka Gakkai Zasshi 104:740–745, 2000

Multiple neurilemmomatosis JAAD 10:744–754, 1984 Myelodysplastic syndrome – subcutaneous eosinophilic necrosis with myelodysplastic syndrome JAAD 20:320–323, 1989 Myelofibrosis – extramedullary hematopoiesis JAAD 32:805, 1995; JAAD 22:334–337, 1990; AD 112:1302–1303, 1976 Myeloma Ann DV 128:753–755, 2001; extramedullary plasmacytoma in myeloma AD 127:69–74, 1991 Myofibroma Myopericytoma Myxoid cyst Nasal polyp 98306 Neural hamartoma Neurilemmoma (Schwannoma) – pink or vascular nodule of the foot Cutis 67:127–129, 2001

Rhabdomyosarcoma Curr Prob Derm 14:41–70, 2002; congenital Ped Derm 20:335–338, 2003; vascular plaque of vulva Ped Derm 34:352–355, 2017 Sclerosing sweat duct carcinoma The Dermatologist November 2013,pp. 47–49 Sebaceous adenoma in AIDS AD 124:489–490, 1988; pedunculated vascular nodule of dorsal penis JAAD 57:S42–43, 2007 Sebaceous epithelioma

Seborrheic keratosis, irritated Self-healing reticulohistiocytosis JAAD 48:S75–77, 2003; JAAD 13:383–404, 1985 Skin tag, irritated – personal observation Spitz nevi, including Spitz nevi mimicking pyogenic granulomas in black children JAAD 23:842–845, 1990; multiple epithelioid Spitz nevi with loss of BAP1 expression – red vascular papules JAMA Derm 149:333–339, 2013 Squamous cell carcinoma – complicating non-Herlitz junctional epidermolysis bullosa – beefy red nodules JAAD 65:780–789, 2011; beefy red nodule of groin – HPV-16+ BJD 170:753–754, 2014; vascular papule of proximal nailfold JAAD 69:253–261, 2013

Neuroblastoma, metastatic Dermatol Therapy 18:104–116, 2005; JAAD 24:1025–1027, 1991

Stewart-Treves angiosarcoma – personal observation

Neurothekeoma JAAD 25:80–88, 1991; AD 129:1505–1510, 1993, Ped Derm 9:272–274, 1992

Sweat gland adenocarcinoma – beefy red nodule BJD 161:694– 696, 2009 Syringocystadenoma papilliferum – pre-­auricular vascular nodule; linear vascular appearing nodules of neck Ped Derm 35:511–512,2018; AD 144:1509–1514, 2008

Neurovascular hamartoma – marker for renal tumors Nodular hidradenoma (clear cell hidradenoma, eccrine acrospiroma, clear cell myoepithelioma) – ulcerated vascular appearing nodule JAAD 76:S46–48, 2017; AD 136:1409–1414, 2000 Non-X histiocytosis AD 124:1254–1257, 1988 Osteosarcoma – primary cutaneous osteosarcoma JAAD 51:S94– 96, 2004 Pilomatrixoma – papule of face Ped Derm 26:195–196, 2009; Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.71; Cutis 50:290–292, 1995; Prog Med 8:826, 1880; including perforating pilomatrixoma (draining nodule) Cutis 44:130–132, 1989; JAAD 35:116–118, 1996; proliferating trichilemmal tumor Plasmacytoma – simulates hemangioma Arch Pathol Lab Med 124:628–631, 2000; eyelid papule Eyelid and Conjunctival Tumors, Shields JA and Shields CL, Lippincott Williams and Wilkins, 1999, p.133; JAAD 19:879–890, 1988 Plexiform fibrohistiocytic tumor AD 131:211–216, 1995 Plexiform neurofibroma Plexiform schwannoma – mimics giant hemangioma BJD 157:838– 839, 2007 Porocarcinoma AD 136:1409–1414, 2000

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Subungual myxoid pleomorphic fibroma 9790115

Trichoblastic carcinoma – giant red beefy tumor BJD 173:1059– 1062, 2015 Umbilical mucosal polyp – vascular umbilical polyp JAMADerm 153:597–598, 2017 Verrucous acanthoma – personal observation Verrucous carcinoma JAAD 32:1–21, 1995 Xanthogranuloma – vascular nodule of sole AD 135:707–712, 1999

PARANEOPLASTIC Cytophagic histiocytic panniculitis – associated with malignant histiocytic syndromes AD 121:910–913, 1985 Eruptive hemangiomatosis – associated with multi-centric Castleman’s disease JAMA Derm 149:204–208, 2013 Granulomatous vasculitis with lymphocytic lymphoma JAAD 14:492–501, 1986 Neutrophilic dermatosis in chronic myelogenous leukemia JAAD 29:290–292, 1993

Progressive nodular histiocytosis Ped Derm 10:64–68, 1993

PRIMARY CUTANEOUS DISEASES

Proliferating trichilemmal cyst Cancer 48:1207–1214, 1981

Acne conglobata

Reticulohistiocytoma, solitary AD 126:665–670, 1990

Acne fulminans

Reticulohistiocytoma of the dorsum (Crosti’s syndrome) – red nodule; low grade B-cell lymphoma

Acne keloidalis

Rhabdoid tumor – ulcerated vascular nodule Ped Derm 28:295–298, 2011; J Cutan Pathol 26:509–515, 1999; Ped Derm 13:468, 1996

Acne vulgaris

Acne rosacea

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Angiolymphoid hyperplasia with eosinophilia – ear lesions AD 143:841–844, 2007; Cutis 44:147–150, 1989; JAAD 12:781–796, 1985; BJD 81:1–14, 1969 Endometriosis (villar nodule) – umbilical multilobulated red nodule AD 148:1331–1332, 2012 Endosalpingosis – ectopic fallopian tube epithelium; umbilical nodule BJD 151:924–925, 2004 Epidermolysis bullosa – excess granulation tissue; junctional EB, Herlitz type, laryngo-onycho-cutaneous syndrome JAAD 58:931– 950, 2008; autosomal dominant epidermolysis bullosa – excess granulation tissue of external auditory canals; mutation in ITGB4 JAMADerm 152:558–562, 2016 Erythema elevatum diutinum JAAD 49:764–767, 2003; AD 129:1043–148, 1993 Granuloma faciale Granuloma gluteale infantum Ped Derm 7:196–198, 1990 Lichen planus Lichen sclerosus et atrophicus – angiokeratoma-like lesions (red-violaceous papules) AD 145:1458–1460, 2009 Membranous lipodystrophy JAAD 24:844–847, 1991 MOTT JAAD 24:208–215, 1991 Progressive nodular fibrosis of the skin JID 87:210–216, 1986 Prurigo nodularis Urethral prolapse – polypoid, edematous, vascular-appearing, violaceous mass at urethral opening JAAD 57:371–392, 2007

SYNDROMES Antiphospholipid antibody syndrome AD 128:847–852, 1992 Bannayan-Riley-Ruvalcaba-Zonana syndrome – hemangiomas, vascular malformations, lipomas, genital hyperpigmentation, supernumerary nipples JAAD 68:189–209, 2013; AD 142:625–632, 2006; AD 132:1214–1218, 1996; Am J Med Genet 44:307–314, 1992 Beckwith-Wiedemann syndrome – hemangiomas; diagonal linear grooves of the ear lobes, preauricular tags or pits, nevus flammeus of central forehead and upper eyelids, macroglossia, macrosomia, omphalocele or other umbilical anomalies Syndromes of the Head and Neck 1990:323–328 Behcet’s syndrome – erythema nodosum-like lesions Blue rubber bleb nevus syndrome – vascular malformation AD 116:924–929, 1996; with phlebectasias Ped Derm 3:304–310, 1986 C syndrome – hemangiomas Birth Defects 5:161–166, 1969 Cardiofaciocutaneous syndrome (Noonan-like short stature syndrome) (NS) – xerosis/ichthyosis, eczematous dermatitis, growth failure, hyperkeratotic papules, ulerythema ophryogenes, seborrheic dermatitis, CALMs, nevi, keratosis pilaris, autosomal dominant, patchy or widespread ichthyosiform eruption, sparse curly short scalp hair and eyebrows and lashes, hemangiomas, acanthosis nigricans, congenital lymphedema of the hands, redundant skin of the hands, short stature, abnormal facies, cardiac defects; gain of function sporadic missense mutations in BRAF, KRAS, MEK1, or MEK2 BJD 164:521–529, 2011; Ped Derm 27:274–278, 2010; JAAD 46:161–183, 2002; Ped Derm 17:231–234, 2000; JAAD 22:920–922, 1990; JAAD 28:815–819, 1993; AD 129:46–47, 1993; port wine stain Clin Genet 42:206–209, 1992 CHILD syndrome – X-linked dominant; strawberry-like papillomatous lesions of toes; linear hyperkeratosis with brownish scaling of fingers and toes AD 142:348–351, 2006; linear hyperkeratotic

plaques of feet (unilateral inflammatory ichthyosiform nevus)with spontaneous involution; macrodactyly; ptychotropism, shortening and absence of limbs, short stature; ipsilateral involvement of bones, lung, kidney, heart, brain; epiphyseal stippling (chondrodysplasia punctata); short stature, scoliosis, clefting of hand or foot, hexadactyly; lateralization and mutations in NSDHL gene which encodes 3-beta hydroxysteroid dehydrogenase JAAD 63:1–22, 2010; BJD 161:714–715, 2009 Classic arthrogryposis:amyoplasia – extensive proliferative hemangioma of the face Congenital generalized fibromatosis JAAD 10:365–371, 1984 Cowden’s syndrome (multiple hamartoma syndrome) – angiomas JAAD 17:342–346, 1987; type 2 segmental Cowden’s disease – keratinocytic soft, thick papillomatous nevus, connective tissue nevi, vascular nevi (including cutis marmorata), angiomas, varicosities, lymphatic hamartomas, lipomas, lipoblastomatosis, hydrocephalus, seizures, hemihypertrophy of limbs, ballooning of toes, bowel polyps, glomerulosclerosis, macrocephaly BJD 156:1089–1090, 2007; Eur J Dermatol 17:133–136, 2007 Cutaneous cavernous malformations with cutaneous angiokeratomas and hemangiomas – mutation in KRIT1 (CCMI) Cutis 96:329– 332, 2015 Edward’s syndrome (Trisomy 18) – capillary hemangiomas J Med Genet 15:48–60, 1978 Epidermal nevus syndrome – hemangiomas Ped Derm 6:316–320, 1989 Fetal alcohol syndrome – short stature, angiomas, hypertrichosis JAAD 46:161–183, 2002; Ped Derm 11:178–180, 1994 Goltz’s syndrome (focal dermal hypoplasia) – painful exophytic granulation tissue BJD 160:1103–1109, 2009; asymmetric linear and reticulated streaks of atrophy and telangiectasia; yellow-red nodules; raspberry-like papillomas of lips, perineum, acrally, at perineum, buccal mucosa; xerosis; scalp and pubic hair sparse and brittle; short stature; asymmetric face; syndactyly, polydactyly; ocular, dental, and skeletal abnormalities with osteopathia striata of long bones JAAD 25:879–881, 1991; raspberry-like papillomas; mutation in PORCN gene (encodes transmembrane endoplasmic reticulum proteins that target WNT signaling proteins Gorham’s syndrome (hemangiomas with osteolysis) (disappearing bone disease) – violaceous vascular plaque with overlying telangiectasias of back, neck, and chest; cutaneous vascular lesions with replacement of bone by venous malformations JAAD 56:S21– 25, 2007; JAMA 252:1449–1451, 1984; Am J Dis Child 132:715– 716, 1978; AD 92:501–508, 1965; with Kasabach-Merritt syndrome JAAD 29:117–119, 1993 Hemangiomas of the face and anterior trunk associated with sternal clefting, median abdominal raphe (sternal malformation vascular dysplasia syndrome) Ped Derm 10:71–76, 1993; Am J Med Genet 21:177–186, 1985 Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) Am J Med 82:989–997, 1987; NEJM 257:105–109, 1957 Hereditary neurocutaneous angioma (vascular malformations) – hemangiomas, macular vascular anomalies; intracranial arteriovenous malformations Clin Genet 33:44–48, 1988 Hereditary phlebectasia of the lips Hypomelia, hypotrichosis, facial hemangioma syndrome (pseudothalidomide syndrome) – sparse silvery blond hair Am J Dis Child 123:602–606, 1972 IgG4-related disease – cutaneous plasmacytosis (papulonodules); pseudolymphoma; angiolymphoid hyperplasia with eosinophilia; Mikulicz’s disease; psoriasiform dermatitis; morbilliform eruption; hypergammaglobulinemic purpura; urticarial vasculitis; ischemic

Nodules, Red or Violaceous, Vascular Appearance digits; Raynaud’s disease and digital gangrene BJD 171:929,959– 967, 2014 Infantile hemangiomatosis Kasabach-Merritt syndrome – associated with Kaposiform hemangioendothelioma or tufted angioma; enlargement, tenderness, induration, and ecchymosis occur within the vascular lesion; consumptive coagulopathy with hemorrhage Ped Derm 11:79–81, 1994 Klippel-Trenaunay-Weber syndrome Clin Exp Derm 12:12–17, 1987 Laryngo-onycho-cutaneous syndrome – autosomal recessive type of junctional epidermolysis bullosa; skin ulceration with prominent granulation tissue, early hoarseness and laryngeal stenosis; scarred nares; chronic erosion of corners of mouth (giant perleche); paronychia with periungual inflammation and erosions; onycholysis with subungual granulation tissue and loss of nails with granulation tissue of nail bed, conjunctival inflammation with polypoid granulation tissue, and dental enamel hypoplasia and hypodontia; only in Punjabi families; mutation in laminin alpha-3 (LAMA3A) BJD 169:1353–1356, 2013; Ped Derm 23:75–77, 2006; Biomedica 2:15–25, 1986; Ped Derm 24:306–308, 2007; Ped Derm 23:75–77, 2006; Cornea 20:753–756, 2001; Arch Dis Child 70:319–326, 1994; JAAD 29:906–909, 1993; Clin Dysmorphol 1:3–14, 1992; Eye 5:717–722, 1991; Lipoid proteinosis Lumbosacral hemangiomas, tethered cord, and multiple congenital anomalies (occult spinal dysraphism) Pediatrics 83:977–980, 1989; AD 122:684–687, 1986; sacral hemangiomas, imperforate anus, genitourinary developmental defects AD 122:684–687, 1986 Macrocephaly with cutis marmorata, hemangioma, and syndactyly syndrome – macrocephaly, hypotonia, hemihypertrophy, hemangioma, cutis marmorata telangiectatica congenita, internal arteriovenous malformations, syndactyly, joint laxity, hyperelastic skin, thickened subcutaneous tissue, developmental delay, short stature, hydrocephalus Ped Derm 16:235–237, 1999; Clin Dysmorphol 6:291–302, 1997 Maffucci’s syndrome – enchondromas and hemangiomas Ped Derm 12:55–58, 1995; BJD 96:317–322, 1977 Melorheostosis – cutaneous lesions resemble linear morphea overlying bony lesions (endosteal bony densities resembling candle wax) with angiomas and arteriovenous abnormalities J Bone and Joint Surg 61:415–418, 1979; BJD 86:297–301, 1972 Muir-Torre syndrome Multiple cutaneous hemangiomas, right aortic arch, and coarctation of the aorta Neurofibromatosis Neurofibromatosis 1:137–145, 1988 Ollier’s syndrome – enchondromas only J Neurol 235:376–378, 1988 Pallister-Hall syndrome – hemangiomas Am J Med Genet 7:75–83, 1980 Patau syndrome (Trisomy 13) – hemangiomas of forehead; localized scalp defects G Ital DV 121:25–28, 1986; J Genet Hum 23:83–109, 1975 PHACES syndrome – posterior fossa malformation (Dandy-Walker malformation), large facial hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects (atrial septal defect), eye abnormalities, sternal clefting or supraumbilical raphe J Pediatr 139:117–123, 2001; AD 132:307–311, 1996; J Pediatr 122:379–384, 1993; Ped Derm 5:263–265, 1988; temporal vascular papules BJD 155:192–194, 2006 Phakomatosis pigmentovascularis type IV A AD 121:651–5, 1985 POEMS syndrome (Crow-Fukase syndrome, Takatsuki syndrome) (PEP syndrome – plasma cell dyscrasia, endocrinopathy,

753

polyneuropathy) – plethora, angiomas (cherry, globular, glomeruloid) presenting as red nodules of face, trunk, and extremities, diffuse hyperpigmentation, hypertrichosis, sclerederma-like changes, either generalized or localized (legs), hyperhidrosis, clubbing, leukonychia, papilledema, pleural effusion, peripheral edema, ascites, pulmonary hypertension, weight loss, fatigue, diarrhea, thrombocytosis, polycythemia, fever, renal disease, arthralgias; osteosclerotic myeloma (IgG or IgA lambda) bone lesions, progressive symmetric sensorimotor peripheral polyneuropathy, hypothyroidism, and hypogonadism; peripheral edema, thrombocytosis, cutaneous angiomas, blue dermal papules associated with Castleman’s disease (benign reactive angioendotheliomatosis), maculopapular brown-violaceous lesions, purple nodules; papilledema JAAD 58:671–675, 2008; JAAD 55:149–152, 2006; JAAD 44:324–329, 2001, JAAD 40:808–812, 1999; AD 124:695–698, 1988, Cutis 61:329–334, 1998; JAAD 21:1061– 1068, 1989; JAAD 12:961–964, 1985; Nippon Shinson 26:2444– 2456, 1968; JAAD 55:149–152,2006; JAAD 44:324–329, 2001; JAAD 21:1061–1068, 1989; JAAD 12:961–964, 1985, AD 124:695–698, 1988, Cutis 61:329–334, 1998; JAAD 40:808–812, 1999; glomeruloid hemangioma – lesion of multicentric Castleman’s disease associated with POEMS syndrome; intralesional protein deposits BJD 148:1276–1278, 2003; Am J Surg Pathol 14:1036–1046, 1990 Proteus syndrome – port wine stains, subcutaneous hemangiomas and lymphangiomas, lymphangioma circumscriptum, hemihypertrophy of the face, limbs, trunk; macrodactyly, cerebriform hypertrophy of palmar and/or plantar surfaces, macrocephaly; verrucous epidermal nevi, sebaceous nevi with hyper- or hypopigmentation AD 140:947–953, 2004; Am J Med Genet 27:99–117, 1987; vascular nevi, soft subcutaneous masses; lipodystrophy, café au lait macules, linear and whorled macular pigmentation JAAD 25:377–383, 1991; Pediatrics 76:984–989, 1985; Am J Med Genet 27:87–97, 1987; Eur J Pediatr 140:5–12, 1983 Reflex sympathetic dystrophy – pseudo-Kaposi’s sarcoma Cutis 68:179–182, 2001 Roberts pseudothalidomide syndrome – superficial capillary hemangiomas of the midface, forehead, ears Prog Clin Biol Res 104:351–356, 1982 Rubinstein-Taybi syndrome – multiple hemangiomas; hypogonadotropic hypogonadism; autosomal dominant; mutations or deletions of chromosome 16p13.3; human cAMP response element binding protein Ped Derm 21:44–47, 2004; JAAD 46:161–183, 2002; JAAD 46:159, 2002 Sweet’s syndrome; with septal granulomatous or neutrophilic lobular panniculitis AD 121:785–788, 1985 Thrombocytopenia-absent radius syndrome (TAR syndrome) – extensive proliferative hemangioma of the face Trichothiodystrophy syndromes – BIDS, IBIDS, PIBIDS – hemangiomas, sparse or absent eyelashes and eyebrows, brittle hair, premature aging, sexual immaturity, ichthyosis, dysmyelination, bird-like facies, dental caries; trichothiodystrophy with ichthyosis, urologic malformations, hypercalciuria and mental and physical retardation JAAD 44:891–920, 2001; Ped Derm 14:441–445, 1997 Partial trisomy 2P – hemangiomas Tuberous sclerosis – angiofibromas Syndromes of the Head and Neck, p. 410–415, 1990 Von Hippel-Lindau syndrome – hemangiomas X-linked hyper IgM syndrome treated with G-CSF – disseminated pyogenic granulomas JAAD 49:105–108, 2003 XXYY syndrome – features of Klinefelter’s; sparse body hair; also multiple angiomas, acrocyanosis, and premature peripheral vascular disease AD 94:695–698, 1966

754 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Xeroderma pigmentosum – short stature, conjunctivitis, photophobia, pyogenic granulomas in toddlers BJD 168:1109–1113, 2013

JAAD 38: 143–175, 1998; JAAD 12:781–796, 1985; following earlobe piercing Ped Derm 31:738–741, 2014 Arteriovenous aneurysms

TRAUMA Chondrodermatitis nodularis chronica helicis Fiddler’s neck JAAD 22:657–663, 1990 Nose piercing with pyogenic granuloma Perniosis Picker’s papule Post-radiation vascular proliferations of breast (atypical vascular lesions of the breast) – erythema; erythema with underlying induration or ulceration, telangiectasias, papules, plaques, nodules, JAAD 57:126–133, 2007 Pseudoaneurysm of face and forehead – pulsatile subcutaneous mass; hematoma with sinus tract communicating with lumen; following Mohs’ surgery JAMADerm 150:546–549, 2014 Pseudo-Kaposi’s sarcoma in reflex sympathetic dystrophy JAAD 22:513–520, 1990

VASCULAR Acquired digital arteriovenous malformation – periungual vascular papule JAAD 56:S122–124, 2007 Acral pseudolymphomatous angiokeratoma of children (APACHE) – unilateral multiple persistent vascular papules on hands and feet; may have keratotic surface or collar JAAD 38:143–175, 1998; BJD 124:387–388, 1991; AD 126:1524–1525, 1990; BJD 119(Suppl):135, 1988 Acroangiodermatitis of Mali – violaceous papules, nodules, and plaques Cutis 86:239–240, 2010; JAAD 37:887–920, 1997; Int J Dermatol 33:179–183, 1994; due to A-V shunts JAAD 21:499–505, 1989; Arch Derm Res 281:35–39, 1989; AD 110:907, 1974; AD 111:1656, 1975; AD 100:297, 1969; associated with chronic venous insufficiency Eur J Vasc Endovasc Surg 24:558–560, 2002; AD 96:176, 1967; AD 92:515–518, 1965 Agminated eruptive pyogenic granuloma-like lesions over congenital vascular stains (capillary malformations) or hemangioma JAMADerm 150:781–783, 2014; Ped Derm 29:186–190, 2012 Angiokeratoma – solitary AD 143:318–325, 2007; acral angiokeratomas of Mibelli in Turner’s syndrome – blue-­black keratotic vascular papules Ped Derm 27:662–664, 2010; circumscriptum; angiokeratoma of Fordyce; Mibelli – acral vascular papules JAAD 45:764–766, 2001; solitary papular, of scrotum or vulva; angiokeratoma corporis diffusum (Fabry’s disease (alpha galactosidase A) NEJM 276:1163–1167, 1967; fucosidosis (alpha-l-fucosidase) – autosomal recessive Rook p. 2639, 1998, Sixth Edition; AD 107:754–757, 1973; Kanzaki’s disease (alpha-Nacetylgalactosidase) – lesions on face and extremities AD 129:460– 465, 1993; beta-mannosidase deficiency; neuraminidase deficiency (sialidosis); aspartylglycosaminuria (aspartylglycosaminidase) Paediatr Acta 36:179–189, 1991; adult-onset GM1 gangliosidosis (beta galactosidase) Clin Genet 17:21–26, 1980; galactosialidosis (combined beta-­galactosidase and sialidase) AD 120:1344–1346, 1984; no enzyme deficiency AD 123:1125–1127, 1987; JAAD 12:885–886, 1985; – telangiectasias or small angiokeratomas; and arteriovenous fistulae without metabolic disorders – papules AD 131:57–62, 1995; eruptive unilateral angiokeratomas AD 144:1663– 1664, 2008 Angiolymphoid hyperplasia with eosinophilia (Kimura’s disease) – papules and/or nodules along hairline AD 136:837–839, 2000;

Arteriovenous fistula with venous hypertension and pseudo-Kaposi’s sarcoma Clin Exp Dermatol 14:289–290, 1989 Arteriovenous hemangioma (cirsoid aneurysm or acral arteriovenous tumor) – associated with chronic liver disease BJD 144:604– 609, 2001 Arteriovenous malformation – vascular nodule with congenital swelling of toe Ped Derm 31:103–104, 2014 Atypical vascular lesion (lymphatic type) – vascular papule of breast JAMA Derm 149:1341–1342, 2013; Am J Clin Pathol 102:757–763, 1994 Benign (reactive) angioendotheliomatosis (benign lymphangioendothelioma, acquired progressive lymphangioma, multifocal lymphangioendotheliomatosis) – present at birth; red brown or violaceous nodules or plaques on face, arms, legs with petechiae, ecchymoses, and small areas of necrosis AD 140:599–606, 2004; JAAD 38:143–175, 1998; AD 114:1512, 1978 Bossed hemangioma with telangiectasia and peripheral pallor AD 134:1145–1150, 1998 Cherry angiomas (Campbell de Morgan spots) Eosinophilic granulomatosis with polyangiitis Combined Kaposiform hemangioendothelioma and combined capillary-venous-lymphatic malformation Ped Derm 28:439–443, 2011 Composite hemangioendothelioma – purple nodule BJD 171:474– 484, 2014 Congenital hemangioma – GNA11 mutation JAMADerm 152:1015– 1020, 2016 Congenital infiltrating giant cell angioblastoma JAAD 37:887–920, 1997 Congenital nonprogressive hemangiomas – blue nodules AD 137:1607–1620, 2001 Congenital plaque type glomuvenous malformations – glomulin gene on 1p21; loss of function mutation; atrophic at birth; livedoid plaques, blue plaques, vascular nodules, red patches, cerebriform, targetoid AD 142:892–896, 2006 Deep vein thrombosis Diffuse neonatal hemangiomatosis (multifocal infantile hemangiomas) JAAD 67:898–903, 2012 Endovascular papillary angioendothelioma (Dabska’s tumor) – vascular nodule JAAD 38:143–175, 1998 Epithelioid angiosarcoma – legs – resembles angiosarcoma JAAD 38:143–175, 1998 Epithelioid hemangioendothelioma JAAD 20:362–366, 1989 Epithelioma hemangioma – entrance of external auditory canal NEJM 373:2070–2077, 2015 Eruptive pseudoangiomatosis – red papules Ped Derm 19:243–245, 2002; BJD 143:435–438, 2000; JAAD 29:857–859, 1993 Erythema induratum Extravascular papillary angioendothelioma Ped Derm 4:332–335, 1987 Exuberant granulation tissue Familial cutaneo-cerebral capillary malformations – hyperkeratotic cutaneous vascular malformations Hum Molec Genet 9:1351–1355, 2000; Ann Neurol 45:250–254, 1999 Familial multiple mucocutaneous venous malformations Human Molec Genet 8:1279–1289, 199: Cell 87:1181–1190, 1996 5q14.3 microdeletions – capillary malformations, arteriovenous malformations, neurologic findings Ped Derm 34:156–159, 2017

Nodules, Red or Violaceous, Vascular Appearance

755

Glomangiomyoma – congenital multiple plaque-like glomangiomyoma Am J Dermatopathol 21:454–457, 1999

Derm 27:588, 2010; J Pediatr 157:795–801, 2010; AD 42:884–888, 2006; Dermatology 214:40–45, 2007

Glomangiopericytoma

Lymphangioendothelioma (red macules and plaques) J Cut Pathol 19:502–505, 1992

Glomus tumor, solitary (glomangioma) – painful pink, purple nodule; multiple or plaque type; hemi-facial JAAD 45:239–245, 2001; Ped Derm 18:223–226, 2001; AD 127:1717–1722, 1991

Lymphangioma circumscriptum Lymphangiosarcoma

Granulation tissue

Lymphangiosarcoma of Stewart-Treves

Hemangioendothelioma

Lymphostasis verrucosa cutis – Milroy’s, etc.

Infantile hemangioma, proliferative (thrombosed); hemangioma of lower lateral cheek associated with airway obstruction; large facial hemangiomas of PHACES syndrome; sacral hemangiomas associated with spinal dysraphism; benign neonatal hemangiomatosis, disseminated neonatal hemangiomatosis Ped Derm 29:64–67, 2012; BJD 169:20–30, 2013; Ped Derm 28:502–506, 2011; Ped Derm 28:267–275, 2011; JAAD 48:477–493, 2003; infantile hemangiomas with unusually prolonged growth phase AD 144:1632–1637, 2008; hemangioma and nevus – personal observation

Malignant angioendotheliomatosis (intravascular malignant lymphoma) (Dabska-type hemangioendothelioma) – red to purple nodules and plaques on trunk and extremities with prominent telangiectasias overlying the lesion JAAD 18:407, 1988; JAAD 38:143–175, 1998; AD 104:320, 1971; AD 84:22, 1961

 Differential diagnosis of hemangioma of infancy Ped Derm 34:331–336, 2017; JAAD 48:477–493, 2003   Arteriovenous malformation   Capillary malformation   Dermatofibrosarcoma protuberans   Encephalocele   Fibrosarcoma    Giant cell fibroblastoma   Kaposiform hemangioendothelioma   Lipoblastoma   Lymphatic malformation   Myofibromatosis   Nasal glioma   Neurofibroma    Non-involuting congenital hemangioma   Pyogenic granuloma    Rapidly-involuting congenital hemangioma   Rhabdomyosarcoma    Spindle cell hemangioendothelioma    Tufted angioma    Venous malformation Hemangiopericytoma – violaceous nodule Ped Derm 23:335–337, 2006; J Bone Joint Surg Br 83:269–272, 2001; AD 116:806, 1980; familial Cancer 61:841–844, 1988

Microvenular hemangioma AD 131:483–488, 1995 Multifocal infantile hemangiomas Ped Derm 33:621–626, 2016 Multifocal lymphangioendotheliomatosis – congenital appearance of hundreds of flat vascular papules and plaques associated with gastrointestinal bleeding, thrombocytopenia with bone and joint involvement; spontaneous resolution J Pediatr Orthop 24:87–91, 2004 Multiple vascular malformations Glomuvenous malformations Blue rubber bleb nevus syndrome Capillary malformation-arteriovenous malformation syndrome Multinucleate cell angiohistiocytoma – red to purple dome shaped 2–15 mm vascular papules, grouped on hands, wrists, and thighs; mimics Kaposi’s sarcoma AD 139:933–938, 2003; JAAD 38:143– 175, 1998 Multiple vascular lesions BJD 171:466–473, 2014  Eruptive pseudoangiomatosis – small red papules following viral infection (Echovirus, cytomegalovirus, Epstein-Barr virus)   Neonatal hemangiomatosis   Blue rubber bleb nevus   Glomuvenous malformations   Maffucci’s syndrome   Hereditary hemorrhagic telangiectasia   Familial mucocutaneous venous malformations   Multifocal lymphangioendotheliomatosis with thrombocytopenia

Hemolymphangioma

Non-involuting congenital hemangioma (NICH) – warm high-flow lesion with coarse telangiectasias over surface; less commonly ulcerated Plast Reconstr Surg 107:1647–1654, 2001; multiple vascular papules Ped Derm 36:720–722, 2019

Histiocytoid hemangioma Dermatology 189:87–89, 1994

Papular angioplasia AD 79:17–31, 1959

Hobnail hemangioma – vascular papules of the nose BJD 146:162– 164, 2002

Partially involuting congenital hemangioma JAAD 70:75–79, 2014

Intravascular papular endothelial hyperplasia (Masson’s intravascular papillary endothelial hyperplasia (pseudoangiosarcoma)) – red or purple papules and nodules of the legs Cutis 59:148–150, 1997; JAAD 10:110–113, 1984; vascular nodule of palmar third finger BJD 166:1147–1149, 2012 Kaposiform hemangioendothelioma of infancy – red-blue tumid swelling; red plaque or nodule with ecchymotic or purpuric border Ped Derm 19:388–393, 2002; JAAD 38:799–802, 1998; AD 133:1573–1578, 1997; Am J Surg Pathol 17:321–328, 1993 Klippel-Trenaunay syndrome – microcystic lymphatic malformation JAMADerm 152:1058–1059, 2016 Lichen aureus LUMBAR syndrome (PELVIS syndrome) – cutaneous infantile hemangiomas of lower body; myelopathy, cutaneous defects, urogenital abnormalities, bony deformities, anorectal abnormalities, arterial anomalies, renal anomalies JAAD 68:885–896, 2013; Ped

PELVIS syndrome (may be part of urorectal septum malformation sequence) – macular telangiectatic patch; larger perineal hemangiomas, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tags AD 142:884–888, 2006 Progressive lymphangioma Polyarteritis nodosa, including cutaneous PAN AD 130:884–889, 1994 Port wine stain – may be associated with underlying vascular malformation; or have pyogenic granuloma, angiokeratoma, arteriovenous malformation, or angiosarcoma develop within it BJD 144:644–645, 2001; AD 120:1453–1455, 1984 Progressive multiple angioma Acta DV 31:304–307, 1951 Pseudo-Kaposi’s sarcoma – Bluefarb-Stewart syndrome JAAD 37:887–920, 1997; after A-V shunt JAAD 21:499–505, 1989; Arch Dermatol Res 281:35–39, 1989; pseudo-Kaposi’s sarcoma – due to acquired arteriovenous fistula J Dermatol 24:28–33, 1997

756 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Pseudoangiosarcoma Pyogenic granuloma BJD 171:466–473, 2014; pedunculated nodule of scalp Ped Derm 26:615–616, 2009; disseminated pyogenic granulomas after exfoliative erythroderma JAAD 32:280– 282, 1995; eruptive pyogenic granulomas JAAD 21:391–394, 1989; Acta DV 50:134–136, 1970; BJD 80:218–227, 1968; due to trauma, retinoids J Dermatol Treat 1:151–154, 1990; after burn and hypogammaglobulinemia BJD 98:461–465, 1978; cyclosporine BJD 132:829–830, 1995; alcoholic cirrhosis Am J Dermatopathol 8:379–385, 1986; of nail bed BJD 163:941–953, 2010; of gingiva JAAD 81:43–56, 2019

NODULES, SKIN COLORED  UTOIMMUNE DISEASES AND DISEASES A OF IMMUNE DYSFUNCTION Chronic granulomatous disease (at immunization site) Connective tissue panniculitis – nodules, atrophic linear plaques of face, upper trunk, or extremities AD 116:291–294, 1980 CREST – plate-like calcinosis cutis – personal observation Dermatitis herpetiformis Clin Exp Dermatol 24:283–285, 1999

Rapidly involuting congenital hemangioma (RICH) – palpable tumor with pale rim, coarse overlying telangiectasia with central depression or ulcer BJD 158:1363–1370, 2008; Ped Dev Pathol 6:495– 510, 2003; Ped Derm 19:5–11, 2002

Dermatomyositis – plate-like calcinosis cutis; calcinosis cutis AD 148:455–462, 2012;

Reactive diffuse dermal angioendotheliomatosis JAAD 45:601–605, 2001

Lupus erythematosus – papulonodular mucinosis – hypopigmented or skin colored papules and nodules Ped Derm 24:585–586, 2007; AD 140:121–126, 2004; Int J Derm 35:72–73, 1996; JAAD 32:199–205, 1995; AD 114:432–435, 1978; lymphadenopathy

Recurrent lobular capillary hemangioma with satellitosis (metastatic pyogenic granulomas) (Warner and Wilson-Jones syndrome) – large central vascular papule surrounded by multiple small vascular papules Cutis 93:125,132, 2014 Retiform hemangioendothelioma – JAAD 42:290–292, 2000; red plaque of scalp, arms, legs, and penis JAAD 38:143–175, 1998 Self-healing pseudoangiosarcoma AD 124:695–698, 1988 Sinusoidal hemangioma Spindle cell hemangioendotheliomas (hemangioma) – multilobulated violaceous nodule AD 142:641–646, 2006; Cutis 62:23–26, 1998 Subungual vascular nodules   Glomus tumor   Pyogenic granuloma   Angiomatous nevus Superficial spreading capillary hemangioma Symplastic hemangioma – vascular nodule growing atop an infantile hemangioma Ped Derm 36:961–962, 2019 Takayasu’s arteritis – erythema nodosum or pyoderma gangrenosum AD 123:796–800, 1987; Churg-Strauss granuloma in Takayasu’s arteritis JAAD 17:998–1005, 1987 Targetoid hemosiderotic hemangioma – brown to violaceous nodule with ecchymotic halo AD 138:117–122, 2002; AD 136:1571–1572, 2000; J Cutan Pathol 26:279–286, 1999; JAAD 32:282–284, 1995; JAAD 41:215–224, 1999 Thrombosed capillary aneurysm – personal observation Tufted angioma – nodularity AD 142:745–751, 2006; of neck Ped Derm 29:778, 2012 Superficial migratory thrombophlebitis Thrombosed capillary aneurysm Tufted angioma AD 145:847–848, 2009; Ped Derm 19:388–393, 2002; JAAD 20:214–225, 1989; Am J Dermatopathol 9:299–300, 1987 Varicocele Vasculitis – small, medium or large vessel vasculitis Vascular malformation Venous lake Verrucous hemangioma Ped Derm 17:213–217, 2000; AD 132:703– 708, 1996; Int J Surg Pathol 2:171–176, 1995; J Derm Surg Oncol 13:1089–1092, 1987; Ped Derm 2:191–193, 1985; AD 96:247–253, 1967; linear JAAD 42:516–518, 2000

panniculitis JAAD 46:S148–150, 2002; nodular cystic fat necrosis Ped Derm 31:588–590, 2014

Morphea – nodular, keloidal (Addisonian keloid) Int J Dermatol 31:422–423, 1992; generalized morphea – keloidal nodules Rheumatoid arthritis – rheumatoid nodules Eur J Radiol 27 Suppl 1:S18–24, 1998; J Rheumatol 6:286–292, 1979; mucinous nodules J Dermatol 26:229–235, 1999; pustular panniculitis J R Soc Med 84:307–308, 1991; rheumatoid vasculitis JAAD 48:311–340, 2003 Sclerederma – nodular sclerederma JAAD 32:343–345, 1995; sclerederma with subcutaneous nodules BJD 101:93–96, 1979; with osteoma cutis Serum sickness – lymphadenopathy Sjogren’s syndrome- parotid swelling Still’s disease (juvenile rheumatoid nodule) Ann Rheum Dis 17:278–283, 1958

CONGENITAL LESIONS Branchial cleft sinus and/or cyst Bronchogenic cyst (overlying the suprasternal notch or manubrium sterni, scapular) – may drain mucoid fluid; may be either sinus tract or subcutaneous nodule AD 142:1221–1226, 2006; JAAD 46:S16– 18, 2002; AD 136:925–930, 2000; Ped Derm 16:285–287, 1999; Ped Derm 12:304–306, 1995; Am J Dermatopathol 13:509–517, 1991; Ann DV 115:855–858, 1988; J Cutan Pathol 12:404–409, 1985; Am J Roentgenol Radium Ther Nucl Med 70:771–785, 1953; J Thoracic Cardiovasc Surg 14:217–220, 1945; skin-colored nodule of chin BJD 143:1353–1355, 2000; papilloma JAAD 11:367–371, 1984 Cervical thyroid (ectopic thyroid gland) NEJM 363:1351, 2010 Chordoma – arise from notochord; skin of perineum, sacrum, buttocks; single or multiple nodules; resemble sacral cysts JAAD 29:63–66, 1993 Congenital cartilaginous rest of the neck – nodule over medial clavicle AD 127:1309–1310, 1991 Congenital cranial fasciitis – giant skin colored nodule Ped Derm 24:263–266, 2007 Congenital fibromatosis of the palm Congenital generalized fibromatosis JAAD 10:365–371, 1984 Congenital lipomatosis – adipose tissue malformation Skeletal Radiol 9:248–254, 1983; J Pediatr Surg 6:742–744, 1971

Nodules, Skin Colored Congenital neurilemmomatosis JAAD 26:786–787, 1992 Cutaneous ciliated cyst – on legs of women AD 136:925–930, 2000 Darwinian tubercle Dermoid cyst – nodule above medial eyebrow Ped Derm 37:40–51, 2020 Ectopic or christomatous salivary gland (heterotopic salivary gland tissue) – skin colored nodule along lower surface of the sternocleidomastoid muscle JAAD 58:251–256, 2008

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Myofibroma – congenital subcutaneous nodule Ped Derm 27:525– 526, 2010 Myopericytoma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010 Myxoid neurothekeoma – skin colored scalp nodules Ped Derm 28:333–334, 2011 Neuroblastoma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010

Fibrosarcoma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010

Neurofibroma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010

Fibrous hamartoma of infancy – skin colored plaque with hypertrichosis and hyperhidrosis Ped Derm 32:533–535, 2015; congenital subcutaneous nodule Ped Derm 27:525–526, 2010; solitary nodule on shoulder, arm, axilla JAAD 54:800–803, 2006; JAAD 41:857– 859, 1999; Ped Derm 13:171–172, 1996; AD 125:88, 1989; J Pathol Bacteriol 72:149–154, 1956   Differential diagnosis includes: Ped Derm 32:533–535, 2015   Infantile fibromatosis   Fibrolipoma    Calcifying aponeurotic fibroma   Myofibroma   Rhabdomyosarcoma   Infantile fibrosarcoma    Inclusion body fibromatosis    Juvenile hyaline fibromatosis   Histiocytoma   Dermatofibrosarcoma protuberans    Gardner syndrome-associated fibroma   Dermatomyofibroma    Fibroblastic connective tissue nevus

Neuroglial heterotopia (encephaloceles that lost intracranial connection) – red nodule of nasal root; skin colored nodule; red blue firm non-compressible nodule (nasal glioma); intranasal polypoid masses; and rudimentary or atretic encephaloceles Ped Derm 32:161–170, 2015

Foregut cystic developmental malformation of scapula – soft skin colored nodule of scapula Ped Derm 29:363–364, 2012

Striated muscle hamartoma (rhabdomyomatous mesenchymal hamartoma) – skin colored papule of upper chest; may be single or multiple, dome-shaped, pedunculated or filiform Ped Derm 16:65–67, 1999

Hemangioma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010 Heterotopic brain tissue – skin colored scalp nodule Dermatol Therapy 18:104–116, 2005 Congenital xanthogranulomas Ped Derm 35:582–587, 2018   Yellow scalp nodule   Ulcerated pink nodule   Subcutaneous nodule with pink papules   Brown-gray patch with pink yellow papules   Atrophic patch with yellow macules and papules

Nevus lipomatosus superficialis – congenital exophytic nodule Ped Derm 34:367–368, 2017; Arch Dermatol Syphil 130:327–333, 1921 Nodular macroglobulinosis JAAD 77:1145–1158, 2017 Palisaded encapsulated neuroma – skin colored papule of face Cutis 92:167, 177–178, 2013 Pyramidal lobe of thyroid gland Rhabdomyosarcoma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010 Solitary congenital calcified nodule of ear Spinal dysraphism, occult – with overlying connective tissue nevus (skin colored plaque), protrusion, dimple, sinus, lipoma, faun tail nevus, dermoid cyst, hemangioma, port wine stain BJD 156:1065– 1066, 2007; AD 114:573–577, 1978; AD 112:1724–1728, 1976

Subcutaneous fat necrosis – subcutaneous tumid mass Ped Derm 30:120–123, 2013 Supernumerary breast – accessory supernumerary axillary breast and nipple with breast carcinoma Cutis 87:300–304, 2011 Vestigial tail Arch J Dis Child 104:72–73, 1962 Wattle (cutaneous cervical tag) AD 121:22–23, 1985

Juvenile xanthogranuloma – congenital plaque Ped Derm 29:217– 218, 2012

DEGENERATIVE DISORDERS

Leiomyoma – congenital subcutaneous nodule Ped Derm 27:525– 526, 2010

Frontal mucocele – skin colored nodule of forehead JAAD 51:1030– 1031, 2004

Leiomyosarcoma – congenital subcutaneous nodule Ped Derm 27:525–526, 2010

Groin hernia   Direct (acquired) hernia   Femoral hernia   Indirect (congenital)hernia   Obturator hernia   Perineal hernia

Lipoma – deep forehead lipoma Ped Derm 37:520–523, 2020; congenital vulvar lipoma with accessory labioscrotal fold – labial enlargement with subcutaneous nodule Ped Derm 28:424–428, 2011 Lipomyelomeningocele (lower back) Ped Derm 26:688–695, 2009   vs. Angiomatous nevi    True tail in newborn Ped Derm 12:263–266, 1995    Perirectal inflammatory lesions    Giant cell tumors of the sacrum Meningocele Myelomeningocele Ped Derm 26:688–695, 2009

Baker’s cyst

Linea alba (epigastric)hernia Muscle herniation – anterior tibialis muscle herniation – pretibial skin colored compressible nodule Ped Derm 36:664–667, 741–742, 2019 Spigelian (linea semilunaris) hernia Transsternal gastric hernia NEJM 370:1440, 2014 Umbilical hernia (abdominal hernia)

758 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

DRUG-INDUCED

Povidone panniculitis (polyvinyl pyrrolidone) AD 116:704–706, 1980

Anti-HIV drugs, including nucleoside reverse transcriptase inhibitors, protease inhibitors, and non-nucleoside reverse transcriptase inhibitors – lipoatrophy, lipohypertrophy, gynecomastia; with metabolic syndrome JAAD 63:549–561, 2010

Silica granuloma AD 127:692–694, 1991

Anti-retroviral agents – scalp nodules NEJM 352:63, 2005 BCG – disseminated BCG infection AD 143:1323–1328, 2007

Silicone – silicone granulomas with facial nodules at crow’s feet BJD 152:1064–1065, 2005; Derm Surg 29:429–432, 2003; skin colored nodules of lower legs – liquid silicone migration from augmentation to buttocks JAAD 64:1–34, 2011; firm skin colored papules of dorsum of hand after rupture of breast implants AD 147:1215–1220, 2011

Corticosteroid – corticosteroid granuloma, resembling rheumatoid nodule Am J Dermatopathol 4:199–203, 1982; steroid atrophy Drug reaction with eosinophilia and systemic symptoms (DRESS) – lymphadenopathy, morbilliform eruption, cheilitis (crusted hemorrhagic lips), diffuse desquamation, areolar erosion, periorbital dermatitis, vesicles, bullae, targetoid plaques, purpura, pustules, exfoliative erythroderma, facial edema JAAD 68:693–705, 2013; Efavirenz – HIV and HAART; bullfrog neck (HIV lipodystrophy) AD 146:1279–1282, 2010 Insulin – insulin granuloma, zinc-induced Clin Exp Dermatol 14:227–229, 1989; lipohypertrophic insulin lipodystrophy JAAD 19:570, 1988 Interferon beta 1a – calcified subcutaneous nodules BJD 157:624– 625, 2007 Iodide mumps – giant acute inflammatory swelling of submandibular, sublingual, or parotid glands Ann Int Med 145:155–156, 2006; Circulation 104:2384, 2001; Acta Radiol 36:82–84, 1995; Am J Roentgenol 159:1099–1100, 1992; JAMA 213:2271–2272, 1970; NEJM 255:433–434, 1956

INFECTIONS AND INFESTATIONS Acanthamoeba – subcutaneous nodule J Clin Inf Dis 20:1207– 1216, 1995 Actinomycosis, disseminated Arch Int Med 134:688–693, 1974; primary cutaneous – subcutaneous nodules with draining sinuses Hum Pathol 4:319–330, 1973 African trypanosomiasis – enlargement of posterior cervical lymph nodes (Winterbottom’s sign) AIDS – diffuse infiltrative lymphocytosis syndrome (DILS) – personal observation Alternaria alternata JAAD 52:653–659, 2005; BJD 143:910–912, 2000 Amebiasis Aspergillosis – primary cutaneous aspergillosis JAAD 31:344–347, 1994; subcutaneous granuloma BJD 85(suppl 17):95–97, 1971

Leuprorelin acetate granulomas BJD 152:1045–1047, 2005

Bacillary angiomatosis (Bartonella henselae) Hautarzt 44:361–364, 1993; JAAD 22:501–512, 1990

Methotrexate nodulosis J Dermatol 26:46–464, 1999; JAAD 39:359–362, 1998

Bartonellosis (Bartonella bacilliformis) Clin Inf Dis 33:772–779, 2001

Minocycline-induced p-ANCA+ cutaneous polyarteritis nodosa (vasculitis) – subcutaneous nodules of extremities JAAD 48:311– 340, 2003; JAAD 44:198–206, 2001

BCG – disseminated BCG in X-linked severe combined immunodeficiency Ped Derm 23:560–563, 2006

Protease inhibitor (saquinavir, nelfinavir, indinavir) – buffalo hump, supraclavicular fat pads, angiolipomas JAAD 46:284–293, 2002

Brodie abscess of tibia – Aggregatibacter aphrophilus (facultative gram-negative bacillus anaerobe of oral cavity) Clin Inf Dis 63:1360,1388–1389, 2016

EXOGENOUS AGENTS

Calymmatobacterium granulomatis (Donovanosis) J Clin Inf Dis 25:24–32, 1997

Aluminum – persistent subcutaneous nodules at the injection site (hypersensitivity to vaccine aluminum adjuvant) Ped Derm 35:234– 236, 2018; immunization site granuloma – due to aluminum hydroxide JAAD 52:623–629, 2005; AD 131:1421–1424, 1995; AD 120:1318–1322, 1984

Candida – deep subcutaneous nodules JAAD 80:869–880, 2019; Clin Exp Dermatol 34:106–110, 2009; chronic mucocutaneous candidiasis Ann Rev Med 32:491–497, 1981

Bovine collagen implant J Derm Surg Oncol 9:377–380, 1983 Bullet foreign body reaction – personal observation Foreign body granuloma from IVDA JAAD 13:869–872, 1985

Botryomycosis Cutis 80:45–47, 2007

Cat scratch disease – lymphadenopathy Cestodes (tapeworms) (Echinococcus and cysticercosis) – slow growing solitary subcutaneous nodule of anterior abdominal wall JAAD 73:929–944, 2015

Hair granuloma

Chagas’ disease (Trypanosoma cruzi) – chagoma NEJM 373:456– 466, 2016

Hyaluronic acid (Captique) – hypersensitivity reaction to non-animal stabilized hyaluronic acid; facial nodules JAAD 55:128–131, 2006

Chromobacterium violaceum – subcutaneous nodules JAAD 54:S224–228, 2006

Implanted stones, glass beads of penis JAAD 20:852, 1989

Coccidioidomycosis – primary inoculation Am Rev Resp Dis 117:559–585; 727–771, 1978

Oleomas – multiple subcutaneous oleomas due to injection with sesame seed oil JAAD 42:292–294, 2000 Paraffinoma (sclerosing lipogranuloma) – face, breast, thighs, buttocks Acta Chir Plast 33:163–165, 1991; Plast Reconstr Surg 65:517–524, 1980 Plant thorns – common blackthorn; persistent nodules of wrists and fingers Lancet i:309–310, 1960 Poly L-lactic microspheres (New-Fill), injectable – skin-colored nodules of cheek JAAD 64:1–34, 2011

Coenurosis – metacestode larval stage (coenurus) of tapeworms Taenia multiceps, Taenia serialis, Taenia brauni Clin Inf Dis 56:1293,1347–1348, 2013 Corynebacterium jeikeium – ulcers, subcutaneous nodules Scand J Infect Dis 27:581–584, 1995; JAAD 16:444–447, 1987 Cryptococcosis JAAD 37:116–117, 1997 Cysticercosis (Taenia solium) (Cysticercus cellulosae) – undercooked pork; multiple asymptomatic subcutaneous nodules; multiple

Nodules, Skin Colored red painless nodules of legs; abdominal pain, muscle edema and pain; diarrhea; neurocysticercosis JAAD 73:929–944, 2015; JAAD 43:538–540, 2000; JAAD 25:409–414, 1991; NEJM 330:1887, 1994; JAAD 12:304–307, 1985 Dermatophilus congolensis – contact with infected animals BJD 145:170–171, 2001 Dipetalonemiasis Dirofilariasis, subcutaneous (migratory nodules) – eyelid, scrotum, breast, arm, leg, conjunctiva JAAD 73:929–944, 2015; Cutis 72:269–272, 2003; JAAD 35:260–262, 1996 Echinococcosis – dog tapeworm; hydatid cyst; urticaria, subcutaneous nodules JAAD 73:929–944, 2015; BJD 147:807, 2002; giant intraperitoneal cyst Fascioliasis – (Fasciola hepatica, F. gigantica) – liver fluke; urticarial, jaundice, diarrhea, serpiginous tracts, subcutaneous nodules JAAD 73:929–944, 2015 Filariasis – Wuchereria bancrofti, Brugia malayi, Brugia timori; mosquito vector – first sign is edema, pain, and erythema with swellings of arms, legs, or scrotum Dermatol Clin 7:313–321, 1989 Gnathostomiasis – including urticarial migratory lesions; intermittent migratory swellings and nodules; subcutaneous hemorrhages along tracks of migration; abdominal pain, nausea and vomiting, diarrhea; South East Asia JAAD 73:929–944, 2015; JAAD 73:929–944, 2015; JAAD 11:738–740, 1984; AD 120:508–510, 1984 Granuloma inguinale (donovanosis) (“serpiginous ulcer”) – Calymmatobacterium granulomatis – starts as skin colored subcutaneous nodule which breaks down into vulvar ulcer, vegetative perianal plaques with fistula formation, mutilation, and elephantine changes JAAD 54:559–578, 2006 Histoplasmosis – breast mass NEJM 375:1172–1180, 2016 HIV/AIDS – parotid lymphoepithelial cysts Infectious mononucleosis – cervical lymphadenopathy Leishmaniasis – disseminated cutaneous leishmaniasis – multilobulated skin colored nodules of ears BJD 156:1328–1335, 2007; JAAD 34:257–272, 1996; AIDS-related visceral leishmaniasis BJD 143:1316–1318, 2000 Leprosy – lepromatous leprosy primary neuritic leprosy with nerve abscesses AD 130:243–248, 1994; erythema nodosum leprosum; Lucio’s phenomenon – firm subcutaneous nodules AD 114:1023–1028, 1978; histoid lesions of relapse of lepromatous leprosy Int J Lepr 31:129–142, 1963 Loiasis – Calabar swellings; temporary of arm and hand, and elsewhere; angioedema Lobomycosis (Lacazia loboi) Lyme borreliosis – juxta-articular fibroid nodule in acrodermatitis chronica atrophicans AD 131:1341–1342, 1995 Mansonella perstans – pericardial inflammation, subcutaneous nodules, peritoneal or pleural cavity involvement, angioedema, pruritus, fever, headaches, arthralgias, neurologic symptoms JAAD 75:19–30, 2016 Molluscum contagiosum, giant Mumps – presternal swelling Cutis 39:139–140, 1987; parotid swelling Mycetoma Mycobacterium avium complex – traumatic inoculation panniculitis; disseminated infection in AIDS – nodules, panniculitis BJD 130:785–790, 1994; subcutaneous nodule J Dermatol 25:384–390, 1998

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Mycobacterium chelonae-fortuitum – disseminated nodules AD 123:1603–1604, 1987; single nodule following navel piercing Ped Derm 25:219–222, 2008 Mycobacterium szulgai – diffuse cellulitis, nodules, and sinuses Am Rev Respir Dis 115:695–698, 1977; subcutaneous nodule BJD 142:838–840, 2000 Mycobacterium tuberculosis – tuberculous gumma (metastatic tuberculous ulcer) – firm subcutaneous nodule or fluctuant swelling breaks down to form undermined ulcer; bluish surrounding skin bound to the inflammatory mass; sporotrichoid lesions along draining lymphatics; extremities more than trunk Scand J Infect Dis 32:37–40, 2000; JAAD 6:101–106, 1982; Semin Hosp Paris 43:868–888, 1967; parasternal pulsatile nodule J Clin Inf Dis 22:871–872, 1996; parotid swelling; miliary tuberculosis JAAD 33:433–440, 1995 Mycobacterium ulcerans (Buruli ulcer) – subcutaneous nodule of legs JAAD 54:559–578, 2006; Aust J Dermatol 26:67–73, 1985 Myiasis, furuncular – house fly BJD 76:218–222, 1964; New World screw worm (Cochliomyia), Old World screw worm (Chrysomya), Tumbu fly (Cordylobia) BJD 85:226–231, 1971; black blowflies (Phormia) J Med Entomol 23:578–579, 1986; green bottle (Lucilia), bluebottle (Calliphora), flesh flies (Sarcophaga, Wohlfahrtia) Neurosurgery 18:361–362, 1986; rodent botflies (Cuterebra) JAAD 21:763–772, 1989; human botflies (Dermatobia hominis) Clin Inf Dis 37:542, 591–592, 2003; AD 126:199–202, 1990; AD 121:1195– 1196, 1985; Hypoderma tarandi; bumblebee-like fly of subarctic regions; eggs deposited on reindeer (caribou); larvae penetrate skin, hatch, and result in migratory swellings; ophthalmomyiasis may result in blindness NEJM 367:2456–2457, 2012 North American blastomycosis – subcutaneous nodule AD 143:1323–1328, 2007 Onchocerciasis – onchocercomas AD 140:1161–1166, 2004; Cutis 72:297–302, 2003; JAAD 45:435–437, 2001; Cutis 65:293–297, 2000 Paragonimiasis (Paragonimus westermani, P. szechuanensis, P. bueitunensis) – lung fluke; undercooked crustaceans; painless migratory subcutaneous nodules of abdominal wall, inguinal area, proximal legs; eosinophilic meningitis and encephalitis JAAD 73:929–944, 2015   Migratory subcutaneous nodules JAAD 73:929–944, 2015   Paragonimiasis   Sparganosis   Onchocerciasis Phaeohyphomycosis, subcutaneous JAAD 36:863–866, 1997; J Clin Inf Dis 25:1195, 1997 Plague (Yersinia pestis) – bubonic plague (subcutaneous nodule) JAAD 54:559–578, 2006 Pneumocystis carinii (jirovecii) – classified as fungus (not protozoan); red or skin-colored papules or nodules JAAD 60:897–925, 2009 Polyacrylamide hydrogel fillers in cosmetic surgery – biofilms of Staphylococcus epidermidis and Propionibacterium acnes; nodules and granulomas at sites of injections of fillers Clin Inf Dis 56:1438– 1444, 2013 Protothecosis JAAD 55:S122–123, 2006; AD 142:921–926, 2006; Am J Clin Pathol 77:485–488, 1982; Am J Clin Pathol 61:10–19, 1974 Pseudomonas aeruginosa Cutis 63:161–163, 1999 Rheumatic fever – nodules of occiput, wrist, backs of forearms Indian Heart J 45:463–467, 1993; JAAD 8:724–728, 1983; Arch Pathol 30:70–89, 1940

760 THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1 Rubella – cervical lymphadenopathy Scarlet fever – cervical lymphadenopathy Sparganosis (larvae of tapeworm) – ingestion sparganosis – edematous painful nodules JAMADerm 152:831–832, 2016; Adv Parasitol 72:351–408, 2010; JAAD 15:1145–1148, 1986; S. proliferum – subcutaneous nodules and pruritic papules JAAD 73:929–944, 2015; Am J Trop Med Hyg 30:625–637, 1981; spirometra – muscle, skin, orbits, and brain JAAD 73:929–944, 2015 Sternoclavicular joint septic arthritis J Clin Inf Dis 19:964–966, 1994 Streptocerciasis – Mansonella streptocerca – similar rash to onchocerciasis; acute or lichenified papules with widespread lichenification and hypopigmented macules Subcutaneous phaeohyphomycosis – Exophiala jeanselmei; nodule of leg BJD 150:597–598, 2004

periorbital edema AD 148:755–760, 2012; myalgias, swelling of joints with refusal to walk; erythema and edema of upper and lower eyelids, violaceous periarticular nodules, skin colored nodules of neck and abdomen Am J Dermatopathol 34:699–705, 2012; AD 145:211–212, 2009; JAAD 55:1036–1043, 2006; JAAD 50:S97–100, 2004; AD 131:459–461, 1995 Subcutaneous xanthogranulomatosis JAAD 21:924–929, 1989

INFLAMMATORY DISORDERS Acne keloidalis nuchae Dermatol Clin 6:387–395, 1988; Dissecting cellulitis of the scalp Fibroblastic rheumatism JAAD 66:959–965, 2012

Trichophyton rubrum, invasive – subcutaneous nodule Cutis 67:457–462, 2001

IgG4 disease – multisystem inflammatory disease with papules, plaques, and nodules; parotitis with parotid gland swelling, lacrimal gland swelling, dacryoadenitis, sialadenitis, proptosis; idiopathic pancreatitis, retroperitoneal fibrosis, aortitis; Mikuliczs syndrome, angiolymphadenopathy with eosinophilia, Riedel’s thyroiditis, biliary tract disease, renal disease, meningeal disease, pituitary gland; Kuttner tumor, Rosai-Dorfman disease; elevated IgG4 with plasma cell dyscrasia, diffuse or localized swelling or masses; sclerosing mesenteritis; lymphocytic and plasma cell infiltrates with storiform fibrosis JAAD 75:177–185, 2016

Tropical pyomyositis – Staphylococcus aureus JAAD 54:559–578, 2006

Interstitial granulomatous dermatitis – multiple skin colored papules JAAD 51:S105–107, 2004

Tularemia – bubo; lymphadenopathy

Kimura’s disease (angiolymphoid hyperplasia with eosinophilia) – large subcutaneous swellings of face, neck, extremities Cutis 70:57–61, 2002; large subcutaneous nodule AD 136:837–839, 2000; JAAD 27:954–958, 1992; JAAD 38:143–175, 1998; JAAD 16:143–145, 1987; JAAD 12:781–796, 1985

Subperiosteal abscess – skin colored nodule overlying tibia JAMADerm 150:663–664, 2014 Syphilis – secondary – facial nodule J Clin Inf Dis 23:462–467, 1996; osteitis of the skull JAAD 40:793–794, 1994; tertiary Cutis 59:135–137, 1997; lymphadenopathy; parotid swelling Toxoplasmosis – lymphadenopathy

Tungiasis – Tunga penetrans JAAD 20:941–944, 1989 Visceral larva migrans – Toxocara canis Warts Whipple’s disease – subcutaneous Whipple’s disease JAAD 16:188–190, 1987 Yaws – tertiary – gumma; subcutaneous nodule; overlying skin ulcerates with purulent discharge; atrophic pigmented scars Zygomycosis – subcutaneous zygomycosis (Basidiobolus ranarum) – subcutaneous nodule with edema Derm Clinics 17:151–185, 1999; JAAD 30:904–908, 1994

INFILTRATIVE DISEASES Amyloidosis – nodular tumefactive amyloid; articular amyloid (amyloid arthropathy) – shoulder pad sign NEJM 351:e23, 2004; Scand J Immunol 54:4048, 2001; NEJM 288:354–355, 1973 Cutaneous focal mucinosis (superficial angiomyxoma) – face, trunk, or extremities Am J Surg Pathol 12:519–530, 1988; AD 93:13–20, 1966 Cutaneous mucinosis of infancy – skin-colored rubbery nodules Ped Derm 27:299–300, 2010; AD 116:198–200, 1980 Generalized eruptive histiocytosis Indeterminate cell histiocytosis BJD 153:206–207, 2005 Juvenile xanthogranuloma – subcutaneous nodule of heel Am J Surg Pathol 15:150–159, 1991 Langerhans cell histiocytosis – eosinophilic granuloma Lichen myxedematosus JAAD 33:37–43, 1995 Papular mucinosis – personal observation Reticulohistiocytoma cutis – solitary reticulohistiocytoma Hifuka Gakkai Zasshi 101, 735–742, 1991; destructive arthritis with rheumatoid-like nodules Clin Exp Dermatol 15:1–6, 1990 Self-healing juvenile cutaneous mucinosis – skin-colored papules and nodules of face and acral areas, arthralgias; periarticular papules Ped Derm 31:515–516, 2014; AD 148:755–760, 2012;

Lymph node – lymphadenitis; lymphadenopathy Lymphocytoma cutis – skin colored to plum-red dermal or subcutaneous nodules; idiopathic or due to insect bites, Borrelia burgdorferi, trauma, vaccinations, injected drugs or antigens for hyposensitization, injection of arthropod venom, acupuncture, gold pierced earrings, tattoos, post-zoster scars JAAD 38:877–905, 1998 Malacoplakia Masseter spasm due to hypersensitive mastication muscle syndrome Myositis, focal – painful nodule Cutis 54:189–190, 1994 Myospherulosis JAAD 38:274–275, 1998; AD 127:88–90, 1991; JAAD 21:400–403, 1989 Nodular cystic fat necrosis JAAD 21:493–498, 1989 Nodular fasciitis – of popliteal fossa Cutis 102:26, 31–32, 2018; painful subcutaneous nodule Cutis 92:199–202, 2013; JAAD 40:490–492, 1999; on the head and neck, extremities, or trunk AD 137:719–721, 2001 Nodular pseudosarcomatous fasciitis AD 124:1559–1564, 1988; Arch Pathol Lab Med 73:437–444, 1962 Proliferative fasciitis – multiple rapidly growing painful subcutaneous nodules in children following trauma; spontaneous resolution AD 144:255–260, 2008; JAAD 55:1036–1043, 2006; Cancer 36:1450– 1458, 1975 Cutaneous sinus histiocytosis with lymphadenopathy (RosaiDorfman disease) AD 133:231–236, 1977 Sarcoid – panniculitis JAAD 45:325–361, 2001; subcutaneous (Darier-Roussy) sarcoid Practical Dermatol March 2019:67–70; JAAD 66:699–716, 2012; JAAD 54:55–60, 2006; BJD 153:790–794, 2005; JAAD 44:725–743, 2001; AD 133:882– 888, 1997; Am J Med 85:731–736, 1988; AD 120:1028–1031,

Nodules, Skin Colored 1984; Ann Dermatol Syphil 5:144–149, 1904; pretibial subcutaneous nodule JAMADerm 150:663–664, 2014; subcutaneous sarcoid mimicking breast cancer BJD 146:924, 2002; lymphadenopathy; uveoparotid fever (Heerfordt’s syndrome) – parotid swelling

       

Sclerosing mesenteritis (retractile mesenteritis) – sclerodermoid changes with subcutaneous nodules; now renamed IgG4 disease AD 146:1009–1013, 2010

Pretibial myxedema Cutis 58:211–214, 1996

Sialadenosis – swelling of parotid gland Subcutaneous fat necrosis of the newborn AD 117:36–37, 1981 Tietze’s disease

METABOLIC DISORDERS Abetalipoproteinemia Adiposis dolorosa (Dercum’s disease) – obesity; multiple painful subcutaneous lipomas, acral edema, telangiectasias JAAD 81:1037–1057, 2019 Albright’s hereditary osteodystrophy Alcoholism – parotid enlargement Benign symmetrical lipomatosis Calcinosis cutis – idiopathic; papular or nodular calcinosis cutis secondary to heel sticks Ped Derm 18:138–140, 2001; cutaneous calculus BJD 75:1–11, 1963; extravasation of calcium carbonate solution; metastatic calcification JAAD 33:693–706, 1995; Cutis 32:463–465, 1983; tumoral calcinosis Calciphylaxis (vascular calcification cutaneous necrosis syndrome) – papules or nodules around large joints or flexures JAAD 40:979– 987, 1999; JAAD 33:53–58, 1995; JAAD 33:954–962, 1995;J Dermatol 28:27–31, 2001; Br J Plast Surg 53:253–255, 2000; J Cutan Med Surg 2:245–248, 1998; JAAD 33:954–962, 1995; AD 127:225–230, 1991

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Albright’s hereditary osteodystrophy Fibrodysplasia ossificans progressiva Congenital plate-like osteomatosis Progressive osseous dysplasia

Oxalate granulomas BJD 128:690–692, 1993 Progressive osseous heteroplasia Ped Derm 16:74–75, 1999; AD 132:787–791, 1996; J Bone Joint Surg Am 76:425–436, 1994 Sickle cell anemia – parotid swelling Sitosterolemia – subcutaneous tuberous and tendon xanthomas Ped Derm 17:447–449, 2000 Verrucous xanthoma – skin colored verrucous papule of earlobe Cutis 91:198–202, 2013 Xanthomas with or without fibrosis

NEOPLASTIC DISORDERS Acrochordon, giant Acrospiroma Cutis 58:349–351, 1996 Adenoid cystic carcinoma – scalp papules or nodules Cutis 77:157–160, 2006; JAAD 40:640–642, 1999; giant tumor Cutis 87:237–239, 2011 Adenolipoma JAAD 29:82, 1993 Aggressive angiomyxoma – greater than 5 cm subcutaneous nodule Am J Surg Pathol 7:463–475, 1983 Alveolar soft part sarcoma – tumor of muscle or fascial planes Clin Exp Dermatol 10:523–539, 1985 Angiokeratoma – personal observation Angioleiomyoma JAAD 46:477–490, 2002; subcutaneous nodule of leg, face, trunk, or oral cavity JAAD 38:143–175, 1998 Epstein-Barr virus positive angioleiomyomas in AIDS BJD 147:563–567, 2002

Cerebrotendinous xanthomatosis (cholestanosis)

Angiolipoleiomyoma JAAD 54:167–171, 2006

Chronic renal failure – benign nodular calcification of chronic renal failure JAAD 33:693–706, 1995

Angiomatoid fibrous histiocytoma Ped Derm 26:636–638, 2009; BJD 142:537–539, 2000

Cryoglobulinemia – dermal nodules JAAD 48:311–340, 2003 Cushing’s disease – buffalo hump, supraclavicular fat pads – personal observation

Angiomyolipoma (angiolipoleiomyoma) (face, ear, elbow, toe) AD 139:381–386, 2003; JAAD 29:115–116, 1993; JAAD 23:1093–1098, 1990

Cystinosis – subcutaneous plaque; skin atrophy and telangiectasia mimicking premature aging; normal skin JAAD 62:AB26, 2010

Angiolipoma – arms, legs, abdomen JAAD 38:143–175, 1998; AD 126:666–667, 669, 1990; AD 82:924–931, 1960

Diabetic lipohypertrophy – giant skin colored tumid mass BJD 171:1402–1406, 2014

Angiosarcoma AD 133:1303–1308, 1997

Diabetes mellitus – parotid gland enlargement – personal observation

Apocrine hidrocystomas, congenital – axillary papules in infancy Ped Derm 30:491–492, 2013

Endometriosis, primary cutaneous AD 145:605–606, 2009; Cutis 81:124–126, 2008

Apocrine nevus Ped Derm 12:248–251, 1995

Extramedullary hematopoiesis JAAD 58:703–706, 2008

Baker’s cyst

Gout- tophi Semin Arthritis Rheum 29:56–63, 1999; AD 113:655– 656, 1977 Hyperoxalosis, primary JAAD 46:S16–18, 2002; AD 131:821–823, 1995; AD 125:380–383, 1989; secondary hyperoxalosis – calcified nodules or miliary papules JAAD 49:725–728, 2003 IgM storage papule – knee, elbow AD 128:377–380, 1992; BJD 106:217–222, 1982 Miliaria profunda – skin-colored papules Osteoma cutis – primary miliary osteoma cutis Ped Derm 29:483– 484, 2012; JAAD 24:878–881, 1991; congenital plate-like osteoma cutis; primary multiple miliary osteomas AD 134:641–643, 1998; differential diagnosis of primary osteoma

Apocrine hamartoma Ped Derm 24:346–347, 2007

Atypical fibroxanthoma Cancer 55:172–180, 1985 Basal cell carcinoma, including multiple hereditary infundibulocystic basal cell carcinomas AD 135:1227–1235, 1999 Blastic plasmacytoid dendritic cell neoplasm (blastic natural killer cell lymphoma) – skin colored nodule of scalp JAMA Derm 149:971–972, 2013 Carcinoid tumors Tumori 76:44–47, 1990; primary cutaneous carcinoid JAAD 51:S74–76, 2004 Castleman’s syndrome Chondroid syringoma AD 140:751–756, 2004; Cutis 71:49–55, 2003 Chondromyxoid fibroma – skin colored nodule overlying tibia JAMADerm 150:663–664, 2014

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THE CLINICIAN’S GUIDE TO DERMATOLOGIC DIFFERENTIAL DIAGNOSIS, VOLUME 1

Chordoma, metastatic AD 133:1579–1584, 1997 Clear cell hidradenoma Ped Derm 22:450–452, 2005 Clear cell sarcoma (malignant melanoma of soft parts) – deep subcutaneous nodule BJD 169:1346–1352, 2013 Collagenous fibroma (desmoplastic fibroblastoma) JAAD 41:292– 294, 1999 Connective tissue nevus (collagenoma) JAAD 67:890–897, 2012; JAAD 3:441–446, 1980; familial collagenoma BJD 101:185–195, 1979; Cutis 10:283–288, 1972; AD 98:23–27, 1968   Birt-Hogg-Dube syndrome   Buschke-Ollendorff syndrome   Cowden’s syndrome   Familial cutaneous collagenomas   Down’s syndrome   Tuberous sclerosis Cribriform apocrine carcino