5-Minute Pediatric Consult, 8e (Oct 10, 2018)_(1496381769)_(LWW) 9781496381767

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Pediatric Consult Editor- Ln- Chi-ef

8‘ EDITION

Michael D. Cabana Asscciale Editcrs

Paul R . Brake man Megan L Cur r an Linda A . DiMeglio W. Christopher Galden Robert E . Gold &by Terry Kind Carlton K . K . Lee Jenifer R. Lightdale Camille Sabella Roan E. Tanei

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Wolters Kluwer

The 5-Minute Pediatric Consult

8m EDITION

ASSOCIATE EDITORS Paul R. Brakeman, MD, PhD Associate Professor of Pediatrics Department of Pediatrics University of California, San Francisco Medical Director, Pediatric Kidney Transplant Program UCSF Benioff Children’s Hospitals San Francisco and Oakland San Francisco, California Megan L. Curran, MD Assistant Professor of Pediatrics Department of Pediatrics University of Colorado School of Medicine Attending Physician Section of Rheumatology Children’s Hospital Colorado Denver, Colorado Linda A. DiMeglio, MD, MPH Professor of Pediatrics Department of Pediatrics, Section of Pediatric Endocrinology and Diabetology Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana W. Christopher Golden, MD Assistant Professor of Pediatrics Division of Neonatology Director, Pediatrics Core Clerkship The Johns Hopkins University School of Medicine Neonatologist and Medical Director Newborn Nursery The Johns Hopkins Hospital Baltimore, Maryland Robert E. Goldsby, MD Professor of Clinical Pediatrics University of California, San Francisco Director, Survivors of Childhood Cancer Program UCSF Benioff Children’s Hospital San Francisco San Francisco, California Terry Kind, MD, MPH

Associate Professor of Pediatrics Assistant Dean for Clinical Education The George Washington University Children’s National Health System Washington, DC Carlton K.K. Lee, PharmD, MPH Associate Professor, Pediatrics The Johns Hopkins University School of Medicine Clinical Pharmacy Specialist, Pediatrics PGY-2 Pediatric Pharmacy Residency Program Director Department of Pharmacy The Johns Hopkins Hospital Baltimore, Maryland Jenifer R. Lightdale, MD, MPH Professor of Pediatrics Department of Pediatrics University of Massachusetts Medical School Division Chief, Pediatric Gastroenterology, Hepatology, and Nutrition Chief Quality Officer UMass Memorial Children’s Medical Center Worcester, Massachusetts Camille Sabella, MD Associate Professor of Pediatrics Vice-Chair for Education, Pediatric Institute Director, Center for Pediatric Infectious Diseases Cleveland Clinic Children’s Hospital Cleveland, Ohio Ronn E. Tanel, MD Professor of Clinical Pediatrics Department of Pediatrics University of California, San Francisco Director, Pediatric Arrhythmia Service Division of Pediatric Cardiology UCSF Benioff Children’s Hospital San Francisco, California

The 5-Minute Consult Pediatric , 8 h EDITION

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Acquisitions Editor: Kate Heaney Digital Product Development Editor: Leanne Vandetty Production Project Manager: Bridgett Dougherty Design Coordinator: Teresa Mallon Manufacturing Coordinator: Beth Welsh Marketing Manager: Rachel Mante-Leung Prepress Vendor: Absolute Service, Inc. 8th Edition Copyright © 2019 Wolters Kluwer Copyright © 2015 Wolters Kluwer. Copyright © 2012 Lippincott Williams & Wilkins, a Wolters Kluwer business. Copyright © 2008, 2005 by Lippincott Williams & Wilkins. All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at [email protected], or via our website at lww.com (products and services). 9 8 7 6 5 4 3 2 1 Printed in China

Library of Congress Cataloging-in-Publication Data available from the Publisher upon request. ISBN-13: 978-1-4963-8176-7

This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. LWW.com Cover Photograph by Elisabeth Fall

I dedicate this book to my wife Jen and our children. Thanks for being patient with me while I wrote and edited –PAUL R. BRAKEMAN, MD, PhD To Cewin, Alex, and Abi –MICHAEL D. CABANA, MD, MPH To my parents Donald J. Curran, DO, and Victoria Renz for instilling in me the value of education, to my patients for teaching me on a daily basis, and to Adam for supporting me unconditionally –MEGAN L. CURRAN, MD To my patients, colleagues, friends, and family (especially Bob, Richard, Luke, and Max) who infuse my life with purpose and joy –LINDA A. DIMEGLIO, MD, MPH To Chinessa and Cadence, how wonderful to have a new sister-in-law and niece and to evidence the love between a new mother and child –W. CHRISTOPHER GOLDEN, MD To my family and all of the patients who have allowed me to be part of their lives –ROBERT E. GOLDSBY, MD Thanks to my pediatric and medical education colleagues, my patients, and my Kind-Simon family, all of whom inspire me. Let’s grow together –TERRY KIND, MD, MPH To Joanne, Brendan, Chester, and my parents for all your support –CARLTON K.K. LEE, PHARMD, MPH Thank you to my family, as well as to Michael, Leanne, and all of my colleagues in pediatric GI, for their trust, love, support . . . and patience. “Little by little, a little becomes a lot.” (African Proverb) –JENIFER R. LIGHTDALE, MD, MPH To my family for their love and support and to my father, in memory –CAMILLE SABELLA, MD To Sarah, Meghan, and Lauren –RONN E. TANEL, MD

PREFACE

I

n a December 30, 1976 cover story interview in Rolling Stone magazine, author Maurice Sendak commented, “There’s so much more to a book than just the reading. I’ve seen children touch books, fondle books, smell books, and it’s all the reason in the world why books should be beautifully produced.”1 Anyone who has given a book to a 1-year-old child in clinic has probably witnessed a child touch, smell, and even taste a book. For a young child with a new book, every sense is engaged. My colleagues and I now present a beautifully produced eighth edition of The 5-Minute Pediatric Consult. Unlike Mr. Sendak and his young readers, we don’t expect you to literally smell or taste this book; however, we have produced a beautiful book that figuratively can be consumed at many different levels. For those readers who need just a “taste” of each topic, each chapter is designed to give the reader a quick overview. A clinician in a busy office or emergency department can quickly look up a description of each condition, as well as what key questions to ask in a history, what findings to look for during the examination, and what tests are most important to prioritize to confirm a diagnosis. Each chapter also includes a differential of other diagnoses to consider and a concise summary of treatment options. For clinicians who need more than just a brief taste of information, each chapter also includes more information on the etiology, pathophysiology, risk factors, and prognosis of each condition. Finally, for those who want to heavily consume the topic, there are suggestions for additional reading, as well as potential “frequently asked questions” that add even further depth and flavor to each chapter. There is also a second meaning to Mr. Sendak’s comment that “there’s so much more to a book than just the reading.” Before any reading takes place, there is all the writing and editing that has already been completed. Although each of the chapters is only two pages of reading, each topic represents years of clinical experience as well as countless hours of research, writing, and editing. The authors of these chapters have demonstrated great skill in distilling large amounts of information into an easily accessible 5-minute synopsis or “consult” on a range of clinical topics. The eighth edition of the book, with over 500 topics, also reflects the continuing achievements and ordeals of the field of pediatrics. With improvements in neonatal care, we now introduce a chapter focused on “Follow-up of the NICU Graduate.” With each passing edition, it is also more difficult to find experts on diseases now less common, such as Diphtheria, Measles, Rheumatic Fever, and Reye Syndrome. However, our field also faces new challenges that are represented by new chapters focused on Zika Virus, Chikungunya Virus, Ebola Virus Disease, and even Vaccine Refusal. To organize this effort, I am fortunate to work with a diverse, distinguished, and talented team of associate editors, who have recruited accomplished authors for each topic. This team of associate editors includes Paul R. Brakeman, MD, PhD; Megan L. Curran, MD; Linda A. DiMeglio, MD, MPH; W. Christopher Golden, MD; Robert E. Goldsby, MD; Terry Kind, MD, MPH; Carlton K.K. Lee, PharmD, MPH; Jenifer R. Lightdale, MD, MPH; Camille Sabella, MD; and Ronn E. Tanel, MD. I have learned from each comment on each draft of each chapter they edited and reviewed. I also give special thanks to Angela Scheuerle, MD who reorganized and updated our Syndromes Glossary for this edition. This updated section includes unique identifiers for dozens of genetic conditions, the associated inheritance

pattern, the involved gene(s), mechanism of disease, as well as a description of the associated clinical findings. Finally, I would also like to thank the staff at Wolters Kluwer, especially Leanne Vandetty and Harold Medina, who have helped us present this work so beautifully. We hope this book will continue to be an indispensable resource for health care professionals who care for children. With these acknowledgments, it is a pleasure to welcome you to this new edition of The 5Minute Pediatric Consult. And in the words of Mr. Maurice Sendak once again, “let the wild rumpus start!”2 MICHAEL D. CABANA, MD, MPH San Francisco, 2018

References 1. Cott J. “Maurice Sendak, King of All Wild Things.” Rolling Stone. December 30, 1976:48–59. 2. Sendak M. Where the Wild Things Are. San Francisco, CA: Harper Collins; 1963.

CONTRIBUTING AUTHORS Bethlehem Abebe-Wolpaw, MD Department of Pediatrics Greater Baltimore Medical Center Towson, Maryland Erika L. Abramson, MD, MS† Associate Professor Pediatrics and Healthcare Policy & Research Weill Cornell Medical College New York, New York Dewesh Agrawal, MD† Associate Professor Pediatrics and Emergency Medicine The George Washington University School of Medicine & Health Sciences Director Pediatric Residency Program Children’s National Medical Center Washington, DC Allison L. Agwu, MD, ScM Associate Professor Pediatric and Adult Infectious Diseases Director, Pediatric and Adolescent HIV/AIDS Program Medical Director, Accessing Care Early (ACE) Clinic PI, JHU IMPAACT and ATN The Johns Hopkins University School of Medicine Baltimore, Maryland Jeremy T. Aidlen, MD Associate Professor of Surgery, Pediatrics, and Urology University of Massachusetts Medical School UMass Memorial Children’s Medical Center Worcester, Massachusetts Akinyemi Ajayi, MBBS, FAAP, FCCP, FAASM President, Medical Director Children’s Lung, Asthma and Sleep Associates and The Children’s Sleep Laboratory Medical Director, Florida Pediatric Research Institute Winter Park, Florida

Ibukunoluwa C. Akinboyo, MD Postdoctoral Fellow Pediatric Infectious Disease The Johns Hopkins University School of Medicine Baltimore, Maryland Temitope Akinmboni, MBBS Clinical Assistant Professor, Pediatrics University of Maryland School of Medicine Baltimore, Maryland Noura Al Dhaheri, MBBS Medical Genetics Resident McKusick-Nathans Institute of Genetic Medicine The Johns Hopkins University School of Medicine Baltimore, Maryland Stamatia Alexiou, MD Assistant Professor of Pediatrics Division of Pulmonary Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Brittany B. Allen, MD Clinical Instructor of Pediatrics Pediatric Hospital Medicine University of Michigan C.S. Mott Children’s Hospital Ann Arbor, Michigan Marilee C. Allen, MD Professor of Pediatrics The Johns Hopkins University School of Medicine Co-Director, Infant Developmental Center Kennedy Krieger Institute Baltimore, Maryland Craig A. Alter, MD Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Director, Neuroendocrine Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Lusine Ambartsumyan, MD Assistant Professor of Pediatrics

University of Washington School of Medicine Director, Gastrointestinal Motility Program Seattle Children’s Hospital Seattle, Washington Prina P. Amin, MD Assistant Professor Department of Pediatrics Division of Academic General Pediatrics Weill Cornell Medical College New York, New York Evan J. Anderson, MD Associate Professor Departments of Pediatrics and Medicine Emory University School of Medicine Atlanta, Georgia Lauren Andrade, MD Pediatric Cardiology Fellow Primary Children’s Hospital Salt Lake City, Utah John S. Andrews, MD Associate Dean for Graduate Medical Education University of Minnesota Medical School Minneapolis, Minnesota Ravit Arav-Boger, MD Professor of Pediatrics Division of Infectious Disease Johns Hopkins University School of Medicine Baltimore, Maryland Kaveh Ardalan, MD, MS Instructor Pediatrics and Medical Social Sciences Northwestern University Feinberg School of Medicine Attending Physician Pediatric Rheumatology Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Lisa M. Arkin, MD† Assistant Professor

Department of Dermatology and Pediatrics University of Wisconsin School of Medicine and Public Health Director of Pediatric Dermatology American Family Children’s Hospital Madison, Wisconsin Stephen S. Arnon, MD, MPH Chief, Infant Botulism Treatment and Prevention Program California Department of Public Health Richmond, California Allison M. Ast, MD Pediatric Hematology/Oncology Hospitalist St. Jude Children’s Research Hospital Memphis, Tennessee Darlene M. Atkins, PhD Associate Clinical Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Director, Donald Delaney Eating Disorders Clinic Children’s National Health System Washington, DC Susan W. Aucott, MD Associate Professor Department of Pediatrics Johns Hopkins University Program Director Neonatal-Perinatal Medicine Fellowship The Charlotte R. Bloomberg Children’s Center Baltimore, Maryland J. Christopher Austin, MD Associate Professor of Urology Oregon Health & Science University Division Chief, Pediatric Urology Doernbecher Children’s Hospital Portland, Oregon Philippe F. Backeljauw, MD Professor Department of Clinical Pediatrics Center for Pediatric and Adult Turner Syndrome Care Director, Pediatric Endocrinology Fellowship Program

Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio L. Charles Bailey, MD, PhD Associate Professor of Clinical Pediatrics Department of Pediatrics Perelman School of Medicine University of Pennsylvania Divisions of Hematology & Oncology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Christina B. Bales, MD Assistant Professor of Clinical Medicine Perelman School of Medicine at the University of Pennsylvania Medical Director, Intestinal Rehabilitation Program Division of Gastroenterology, Hepatology, and Nutrition The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Orkun Baloglu, MD Clinical Assistant Professor Department of Pediatrics Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Staff Physician Department of Pediatric Critical Care Medicine Medical Director, Pediatric Critical Care Transport Team Cleveland Clinic Children’s Hospital Cleveland, Ohio Kristin W. Barañano, MD, PhD Assistant Professor Department of Neurology The Johns Hopkins University School of Medicine Baltimore, Maryland Jennifer M. Barker, MD Associate Professor Pediatric Endocrinology University of Colorado Anschutz Medical Campus Program Director Pediatric Endocrinology Fellowship Children’s Hospital Colorado Aurora, Colorado

Meagan Barrett, MD Pediatric Dermatology Fellow Children’s Hospital Los Angeles Los Angeles, California Keisha R. Barton, MD Fellow Division of Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Texas Children’s Hospital Houston, Texas Laurence S. Baskin, MD Frank Hinman, Jr., MD Distinguished Professorship in Pediatric Urology Chief, Pediatric Urology UCSF Benioff Children’s Hospital University of California, San Francisco San Francisco, California Anne S. Bassett, MD, FRCPC Dalglish Chair in 22q11.2 Deletion Syndrome Canada Research Chair in Schizophrenia Genetics and Genomic Disorders (Tier 1, 2009 to 2016) Professor of Psychiatry, University of Toronto Associate Staff, Division of Cardiology, University Health Network Associate Member, Canadian College of Medical Geneticists Director, The Dalglish 22q Clinic for Adults Director, Clinical Genetics Research Program, Centre for Addiction & Mental Health Toronto, Ontario, Canada Hamid Bassiri, MD, PhD Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Attending Physician, Pediatric Infectious Diseases Faculty Member, Center for Childhood Cancer Research The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Irini D. Batsis, MD Pediatric Gastroenterology, Hepatology, and Nutrition Fellow The Charlotte R. Bloomberg Children’s Center Johns Hopkins University Baltimore, Maryland Timothy S. Baumgartner, FS, MC, Lt Col, USAF†

Pediatric Urology Fellow Division of Pediatric Urology The James Buchanan Brady Urological Institute Department of Urology The Johns Hopkins Hospital Baltimore, Maryland Christopher E. Bayne, MD Assistant Professor Department of Urology Division of Pediatric Urology University of Florida College of Medicine Gainesville, Florida Suzanne E. Beck, MD Professor of Clinical Pediatrics Children’s Hospital of Philadelphia University of Pennsylvania School of Medicine Philadelphia, Pennsylvania David K. Becker, MD, MPH, MA, LMFT Clinical Professor of Pediatrics UCSF Osher Center for Integrative Medicine Co-Medical Director, Pediatric Pain Management Clinic UCSF Benioff Children’s Hospital San Francisco San Francisco, California Shashank P. Behere, MD Fellow Nemours Cardiac Center Nemours Alfred I. duPont Hospital for Children Wilmington, Delaware Sidney Kimmel Medical College of Thomas Jefferson University Philadelphia, Pennsylvania ElShadey Bekele, MD, MPH Clinical Instructor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Attending Pediatrician Children’s National Medical Center Washington, DC Kelly A. Benedict, MD

Pediatric Nephrologist Pediatric Kidney Disease and Hypertension Centers Phoenix, Arizona Amanda K. Berry, MSN, CRNP, PhD† Pediatric Nurse Practitioner Division of Urology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Kate Berz, DO Assistant Professor of Pediatrics Divisions of Sports Medicine and Emergency Medicine University of Cincinnati College of Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Anita Bhandari, MD Associate Professor of Pediatrics University of Pennsylvania Director, Pulmonary Inpatient Services The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Vineet Bhandari, MD, DM Professor of Pediatrics, Obstetrics, and Gynecology Drexel University College of Medicine Chief, Section of Neonatal-Perinatal Medicine St. Christopher’s Hospital for Children Philadelphia, Pennsylvania Sumit Bhargava, MD Clinical Associate Professor Department of Pediatrics Stanford University Medical Director Lucile Packard Children’s Hospital Pediatric Sleep Laboratory Palo Alto, California Diana X. Bharucha-Goebel, MD Assistant Professor, Neurology Children’s National Health System Washington, DC Mihir D. Bhatt, MD, FRCPC

Pediatric Hematologist/Oncologist McMaster Children’s Hospital McMaster University Hamilton, Ontario, Canada Samina S. Bhumbra, MD Pediatric Infectious Diseases Fellow Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Cara L. Biddle, MD, MPH Assistant Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Associate Division Chief Division of General Pediatrics and Community Health Children’s National Health System Washington, DC Steven Bin, MD Associate Professor Department of Emergency Medicine and Pediatrics University of California, San Francisco Medical Director Children’s Emergency Department UCSF Benioff Children’s Hospital San Francisco San Francisco, California Mercedes M. Blackstone, MD Associate Professor Department of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Attending Physician Department of Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Seth J. Bokser, MD, MPH Associate Clinical Professor of Pediatrics University of California, San Francisco Pediatric Hospitalist UCSF Benioff Children’s Hospital San Francisco San Francisco, California Brett J. Bordini, MD

Assistant Professor Department of Pediatrics Section of Hospital Medicine Nelson Service for Undiagnosed and Rare Diseases Medical College of Wisconsin Milwaukee, Wisconsin Emily C. Borman-Shoap, MD Assistant Professor of Pediatrics Director, Pediatric Residency Program Vice Chair of Education University of Minnesota Minneapolis, Minnesota Renee D. Boss, MD, MHS Associate Professor Department of Pediatrics Division of Neonatology The Johns Hopkins University School of Medicine Johns Hopkins Berman Institute of Bioethics Baltimore, Maryland John Bower, MD Associate Professor of Pediatrics Associate Professor of Microbiology/Immunology/Biochemistry Northeast Ohio Medical University Rootstown, Ohio Division of Pediatric Infectious Diseases Akron Children’s Hospital Akron, Ohio Alison Boyce, MD Endocrinologist Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda, Maryland Paul R. Brakeman, MD, PhD Associate Professor of Pediatrics University of California, San Francisco Medical Director, Pediatric Kidney Transplant Program UCSF Benioff Children’s Hospital San Francisco and Oakland San Francisco, California

Wendy J. Brickman, MD Associate Professor Department of Pediatrics Division of Endocrinology Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Lee J. Brooks, MD Clinical Professor of Pediatrics Division of Pediatric Pulmonology and Sleep Perelman School of Medicine University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Jeffrey P. Brosco, MD, PhD Professor of Clinical Pediatrics, University of Miami Miller School of Medicine Associate Director, Mailman Center for Child Development Faculty Education Development Director, Department of Pediatrics Director, Population Health Ethics, UM Institute for Bioethics and Health Policy Chair, Pediatric Bioethics Committee, Holtz Children’s Hospital, Jackson Health System Miami, Florida Valerie I. Brown, MD, PhD Associate Professor Department of Pediatrics Division of Pediatric Hematology/Oncology Director, Experimental Therapeutics Director, Pediatric Hematology/Oncology Fellowship Program Attending Physician Hematopoietic Stem Cell Transplant Program Penn State Hershey Children’s Hospital and Penn State College of Medicine Hershey, Pennsylvania Terri Brown-Whitehorn, MD Associate Professor Department of Clinical Pediatrics Division of Allergy and Immunology Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Ann Bruner, MD Medical Director, Residential Youth Services

Mountain Manor Treatment Center Baltimore, Maryland Sara M. Buckelew, MD, MPH Professor of Pediatrics University of California, San Francisco Medical Director, Division of Adolescent and Young Adult Medicine UCSF Benioff Children’s Hospital San Francisco San Francisco, California Cynthia Burke, NNP-BC Clinical Nurse Neonatal Pediatric Nurse Practice University of California, San Francisco San Francisco, California Vera Joanna Burton, MD, PhD Assistant Professor of Neurology and Developmental Medicine Kennedy Krieger Institute The Johns Hopkins University School of Medicine Baltimore, Maryland Melissa A. Buryk, MD, MPH† LCDR, MC, USN Assistant Professor Department of Pediatrics Uniformed Services University of the Health Sciences Associate Program Director Department of Pediatrics Staff Pediatric Endocrinologist Portsmouth Naval Medical Center Portsmouth, Virginia Amaya L. Bustinduy, MD, MPH, PhD, FRCPCH Associate Professor in Tropical Pediatrics Clinical Research Department London School of Hygiene & Tropical Medicine London, United Kingdom Lavjay Butani, MD, MACM Professor Department of Pediatrics Chief of Pediatric Nephrology University of California, Davis

Sacramento, California Katherine A. Butler, MD† Orthopedic Surgery Resident MedStar Union Memorial Hospital Baltimore, Maryland Francesca A. Byrne, MD Volunteer Clinical Faculty Department of Pediatrics Division of Cardiology University of California, Irvine Miller Children’s & Women’s Hospital Long Beach Long Beach, California Susanne M. Cabrera, MD† Assistant Professor Department of Pediatrics Medical College of Wisconsin Children’s Hospital of Wisconsin Max McGee National Research Center for Juvenile Diabetes Milwaukee, Wisconsin Mark P. Cain, MD Robert Garrett Professor of Pediatric Urology Chief, Division of Pediatric Urology Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Andrew C. Calabria, MD Assistant Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Clinical Director, Division of Endocrinology and Diabetes The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Robert M. Campbell Jr., MD Professor of Orthopaedic Surgery University of Pennsylvania Director, Center of Thoracic Insufficient Syndrome Division of Orthopaedics The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Ninfa M. Candela, MD Assistant Professor of Pediatrics, Pediatric Gastroenterology, and Nutrition University of Massachusetts Medical School UMASS Memorial Health Care Worcester, Massachusetts Joseph B. Cantey, MD Assistant Professor of Pediatrics Division of Neonatology Division of Allergy, Immunology, and Infectious Diseases University of Texas Health San Antonio San Antonio, Texas Katie Carlberg, MD Pediatric Hematology Oncology Fellow UCSF Benioff Children’s Hospital Oakland, California Vanessa S. Carlo, MD Clinical Assistant Professor Department of Pediatrics Sidney Kimmel Medical College Assistant Residency Director Jefferson/Nemours Alfred I. duPont Hospital for Children Philadelphia, Pennsylvania Michael C. Carr, MD, PhD Director, Pediatric Urology KIDZ Multispecialty Group Naples, Florida Leslie Castelo-Soccio, MD, PhD Assistant Professor Department of Pediatrics and Dermatology Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Brianna Castillo, MD University of South Florida Health Tampa, Florida Lauren Castner, DO Pediatric Pulmonary Fellow University of Michigan C.S. Mott Children’s Hospital

Ann Arbor, Michigan Elizabeth Candell Chalom, MD Associate Professor, Pediatrics Robert Wood Johnson Barnabas Health Director, Pediatric Rheumatology Saint Barnabas Medical Center Livingston, New Jersey Todd P. Chang, MD, MAcM Associate Professor of Clinical Pediatrics (Educational Scholar) Keck School of Medicine of USC Director Research and Scholarship Division of Pediatric Emergency Medicine Associate Fellowship Director Children’s Hospital Los Angeles Los Angeles, California Raul Chavez-Valdez, MD Assistant Professor of Pediatrics Division of Neonatology Johns Hopkins University Baltimore, Maryland May W. Chen, MD Postdoctoral Fellow Division of Neonatology The Johns Hopkins University School of Medicine The Charlotte R. Bloomberg Children’s Center Baltimore, Maryland Pi Chun Cheng, MD, MS Pediatric Pulmonary Fellow Division of Pulmonary Medicine and Cystic Fibrosis Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania David H. Chi, MD Associate Professor Department of Otolaryngology University of Pittsburgh Clinical Director Department of Pediatric Otolaryngology

Children’s Hospital of Pittsburgh Pittsburgh, Pennsylvania Michael F. Chiang, MD Knowles Professor of Ophthalmology & Medical Informatics and Clinical Epidemiology Vice-Chair (Research), Department of Ophthalmology Casey Eye Institute Oregon Health & Science University Portland, Oregon Eric H. Chiou, MD Assistant Professor of Pediatrics Division of Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Texas Children’s Hospital Houston, Texas Maribeth Chitkara, MD† Associate Professor Department of Clinical Pediatrics Director, Pediatric Medical Student Education Stony Brook Long Island Children’s Hospital Stony Brook, New York Christine S. Cho, MD, MPH, MEd Associate Professor Department of Pediatrics University of Southern California Fellowship and Education Director Division of Emergency Medicine Children’s Hospital Los Angeles Los Angeles, California Angela Y. Choe, MD Hospital Medicine Fellow Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Tyler W. Christman, DO, MS Assistant Professor Department of Clinical Orthopedic Surgery Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana

Esther K. Chung, MD, MPH Professor Department of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University Jefferson Pediatrics/Nemours-Philadelphia Philadelphia, Pennsylvania Director, Department of Newborn Nursery Director, Advocacy and Community Partnerships Nemours Alfred I. duPont Hospital for Children Wilmington, Delaware Melissa G. Chung, MD Assistant Professor Department of Pediatrics The Ohio State University Director of Critical Care Neurology Division of Neurology and Critical Care Medicine Nationwide Children’s Hospital Columbus, Ohio Gwynne D. Church, MD Associate Professor Department of Pediatric Pulmonology University of California, San Francisco Medical Director, Pediatric Sleep Lab UCSF Benioff Children’s Hospital San Francisco San Francisco, California Onur Cil, MD, PhD Clinical Fellow Department of Pediatrics, Division of Nephrology University of California, San Francisco San Francisco, California Melissa L. Cirillo, MD Assistant Professor of Pediatrics Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Stephanie Clark, MD, MPH Assistant Professor of Pediatrics Division of Nephrology Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania Jessica P. Clarke-Pounder, MD Neonatologist Atrium Health Levine Children’s Hospital Charlotte, North Carolina Ronald D. Cohn, MD, FACMG Associate Professor Department of Pediatrics and Molecular Genetics University of Toronto Chief, Clinical and Metabolic Genetics Department of Pediatrics The Hospital for Sick Children Toronto, Ontario, Canada Nailah Coleman, MD, FAAP, FACSM Assistant Professor Department of Pediatrics The George Washington University Medical Center Pediatric Attending The Goldberg Center for Community Pediatric Health Children’s National Health System Washington, DC Ellen Lancon Connor, MD Professor Department of Pediatric Endocrinology and Diabetes University of Wisconsin-Madison Co-Director, Adolescent PCOS Clinic American Family Children’s Hospital Madison, Wisconsin Stephen H. Contompasis, MD Emeritus Professor Department of Pediatrics University of Vermont College of Medicine Burlington, Vermont Hillary L. Copp, MD, MS Assistant Professor Pediatric Urologist Department of Urology University of California, San Francisco

San Francisco, California Randy Q. Cron, MD, PhD Arthritis Foundation, Alabama Chapter Endowed Professor of Pediatrics Director, Pediatric Rheumatology University of Alabama at Birmingham Children’s of Alabama Birmingham, Alabama Megan L. Curran, MD Associate Professor of Pediatrics Department of Pediatrics University of Colorado School of Medicine Attending Physician Section of Rheumatology Children’s Hospital Colorado Aurora, Colorado Sandra Cuzzi, MD Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Hospitalist Division Children’s National Medical Center Washington, DC Rajesh K. Daftary, MD, MPH Assistant Professor, Pediatric Emergency Medicine University of California, San Francisco Medical Director of Pediatric Emergency Medicine Zuckerberg San Francisco General Hospital San Francisco, California Bertil Damato, MD, PhD, FRCOphth Director, Ocular Oncology Service Professor of Ophthalmology and Radiation Oncology University of California, San Francisco San Francisco, California Yalda Serena Dastmalchi, MD Resident Physician, Emergency Medicine Maimonides Medical Center Brooklyn, New York Diva D. De León, MD, MSCE

Associate Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Director, Congenital Hyperinsulinism Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Jeannine Del Pizzo, MD Assistant Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Attending Physician, Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Michelle Denburg, MD, MSCE Professor of Pediatrics Department of Pediatrics Division of Nephrology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Sanyukta Desai, MD Clinical Fellow, Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Craig C. DeWolfe, MD, MEd Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Director, Pediatric Medical Student Education Pediatric Hospitalist Children’s National Health System Washington, DC Katherine Deye, MD Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Child Abuse Pediatrician Freddie Mac Foundation Child and Adolescent Protection Center Children’s National Medical Center Washington, DC Johana Diaz, MD

Assistant Professor, Pediatrics University of Maryland School of Medicine Baltimore, Maryland Francis J. DiMario Jr., MD Professor Department of Pediatrics and Neurology University of Connecticut Associate Chair Academic Affairs Department of Pediatrics Medical Director, Human Research Protection Program Chief Emeritus, Division of Pediatric Neurology Connecticut Children’s Medical Center Hartford, Connecticut Michael DiSandro, MD Professor of Urology UCSF Benioff Children’s Hospital San Francisco, California Danielle G. Dooley, MD, MPhil, FAAP Assistant Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Medical Director Community Affairs and Population Health Child Health Advocacy Institute Children’s National Health System Washington, DC Rebecca A. Dorner, MD Postdoctoral Fellow Division of Neonatology The Johns Hopkins Hospital The Charlotte R. Bloomberg Children’s Center Baltimore, Maryland Morna J. Dorsey, MD, MMSc Professor of Pediatrics Section Chief, Allergy & Immunology Division of Allergy, Immunology, and BMT University of California, San Francisco (UCSF) UCSF Benioff Children’s Hospital San Francisco San Francisco, California

Monica Dowling, PhD Assistant Professor of Clinical Pediatrics University of Miami Miller School of Medicine Mailman Center for Child Development Miami, Florida Colleen A. Hughes Driscoll, MD Assistant Professor Department of Pediatrics Division of Neonatology University of Maryland School of Medicine Baltimore, Maryland Nancy A. Drucker, MD Associate Professor of Pediatrics Robert Larner, MD College of Medicine at the University of Vermont Pediatric Cardiology University of Vermont Children’s Hospital Burlington, Vermont Steven G. DuBois, MD, MS Associate Professor Department of Pediatrics Harvard Medical School Director, Experimental Therapeutics Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Boston, Massachusetts Erin Dunbar, MD, MSc Pediatric Emergency Medicine Fellow C.S. Mott Children’s Hospital Michigan Medicine Ann Arbor, Michigan Deborah B. Ehrenthal, MD, MPH Associate Professor of Obstetrics & Gynecology and Population Health Sciences University of Wisconsin-Madison Director, Division of Reproductive and Population Health School of Medicine and Public Health Madison, Wisconsin Scott A. Elisofon, MD† Instructor Department of Pediatrics

Harvard Medical School Attending Physician Division of Gastroenterology, Hepatology, and Nutrition Medical Director, Liver Transplant Program Boston Children’s Hospital Boston, Massachusetts Gary A. Emmett, MD, FAAP Professor of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Heidi Engel, PT, DPT Assistant Clinical Professor Department of Physical Health and Science University of California, San Francisco San Francisco, California Erica A. Eugster, MD Professor of Pediatrics Chief, Division of Pediatric Endocrinology Riley Hospital for Children at Indiana University Health Indiana University School of Medicine Indianapolis, Indiana Nicholas F. Evageliou, MD Associate Professor of Clinical Pediatrics University of Pennsylvania Division of Oncology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Stephen J. Falchek, MD Pediatric Neurologist and Clinical Neurophysiologist Director, Pediatric Neurology Residency and Epilepsy Fellowship Programs Nemours Alfred I. duPont Hospital for Children Sidney Kimmel Medical College of Thomas Jefferson University Wilmington, Delaware Marni J. Falk, MD Executive Director, Mitochondrial Medicine Frontier Program Associate Professor, Division of Human Genetics, Department of Pediatrics University of Pennsylvania Perelman School of Medicine Children’s Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania Olanrewaju O. Falusi, MD, FAAP Assistant Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Associate Medical Director for Municipal and Regional Affairs Child Health Advocacy Institute Children’s National Health System Washington, DC Azadeh Farzin, MD, MHS Assistant Professor of Pediatrics and International Health Johns Hopkins University International Center for Maternal and Newborn Health Baltimore, Maryland Rima Fawaz, MD Instructor in Pediatrics Harvard Medical School Medical Director, Intestinal and Multivisceral Transplant Division of Gastroenterology, Hepatology, and Nutrition Boston Children’s Hospital Boston, Massachusetts Pamela D. Fazzio, MD Fellow Pediatric Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Jessica L. Fealy, MD Clinical Instructor, Division of General Pediatrics Michigan Medicine C.S. Mott Children’s Hospital Ann Arbor, Michigan Kristen A. Feemster, MD, MPH, MSHP Adjunct Associate Professor of Pediatrics, Infectious Diseases Perelman School of Medicine at the University of Pennsylvania Director of Research, Vaccine Education Center The Children’s Hospital of Philadelphia Medical Director, Acute Communicable Diseases and Immunization Programs Philadelphia Department of Public Health, Division of Disease Control Philadelphia, Pennsylvania

Daniel E. Felten, MD, MPD Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Assistant Medical Director Children’s Health Center Children’s National Medical Center Washington, DC James H. Feusner, MD Professor of Pediatrics Department of Hematology-Oncology UCSF Benioff Children’s Hospital Oakland Oakland, California Amy G. Filbrun, MD, MS Clinical Associate Professor Department of Pediatrics Pulmonary Division University of Michigan C.S. Mott Children’s Hospital Ann Arbor, Michigan Craig J. Finlayson, MD Assistant Professor of Orthopaedic Surgery Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Anna B. Fishbein, MD, MSc Assistant Professor of Pediatrics Division of Allergy & Immunology Northwestern University Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Michael J. Fisher, MD Associate Professor Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania Chief, Neuro-Oncology Section Director, Neurofibromatosis Program Director, Neuro-Oncology Fellowship Program Center for Childhood Cancer Research and Division of Oncology The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania Laurie N. Fishman, MD† Assistant Professor Department of Pediatrics Harvard Medical School Director, Medical Education for Gastroenterology Division of Gastroenterology and Nutrition Boston Children’s Hospital Boston, Massachusetts Jonathan T. Fleenor, MD, FACC, FAAP Assistant Professor Department of Pediatrics Eastern Virginia Medical School Medical Director Department of Pediatric Cardiology Children’s Hospital of the King’s Daughters Norfolk, Virginia Leah R. Fleming, MD Genetics and Metabolic Clinic St. Luke’s Children’s Hospital Boise, Idaho Jay Fong, MD Assistant Professor of Pediatrics Division of Pediatric Gastroenterology, Hepatology, and Nutrition University of Massachusetts Medical School Worcester, Massachusetts Michelle Forcier, MD, MPH Associate Professor Department of Pediatrics Division of Adolescent Medicine Department of Pediatrics The Warren Alpert Medical School of Brown University Providence, Rhode Island Craig M. Forester, MD, PhD† Assistant Adjunct Professor Department of Pediatric Hematology/Oncology and HSCT University of California, San Francisco UCSF Benioff Children’s Hospital

San Francisco, California Sara F. Forman, MD Assistant Professor of Pediatrics Harvard Medical School Clinical Chief, Division of Adolescent/Young Adult Medicine Boston Children’s Hospital Boston, Massachusetts Karen R. Fratantoni, MD, MPH Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Medical Director Complex Care Program Children’s National Medical Center Washington, DC Melissa B. Freizinger, PhD† Instructor, Department of Psychiatry Harvard Medical School Associate Director Eating Disorder Program Adolescent Medicine Boston Children’s Hospital Boston, Massachusetts Ilona J. Frieden, MD Professor of Dermatology and Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Linda Y. Fu, MD, MS Associate Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Director, Academic Development Division of General and Community Pediatrics Children’s National Health System Washington, DC Susan Fuchs, MD Professor Department of Pediatrics

Northwestern University Feinberg School of Medicine EMS Medical Director Division of Emergency Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Ramsay L. Fuleihan, MD Professor of Pediatrics Division of Allergy & Immunology Ann & Robert H. Lurie Children’s Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago, Illinois Nora M. Fullington, MD Assistant Professor of Surgery Department of Surgery University of Massachusetts Medical School UMass Memorial Medical Center Worchester, Massachusetts John S. Fuqua, MD Professor Department of Clinical Pediatrics Section of Pediatric Endocrinology Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Steven J. Fusillo, MD Fellow Pediatric Gastroenterology Division of Gastroenterology, Hepatology, and Nutrition The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Payal K. Gala, MD Assistant Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Attending Physician Pediatric Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Theodore J. Ganley, MD

Associate Professor of Orthopedic Surgery Perelman School of Medicine at the University of Pennsylvania Director of Sports Medicine The Children’s Hospital of Philadelphia Sports Medicine and Performance Center Philadelphia, Pennsylvania George D. Gantsoudes, MD Assistant Professor of Orthopaedic Surgery Georgetown University Pediatric Specialists of Virginia Fairfax, Virginia Alejandro V. Garcia, MD Assistant Professor Department of Surgery The Johns Hopkins University School of Medicine Johns Hopkins Children’s Center Baltimore, Maryland Ana Catarina Garnecho, MD Assistant Professor of Pediatrics Developmental–Behavioral Pediatrics New England Pediatric Institute of Neurodevelopment Department of Pediatrics Women & Infants Hospital The Warren Alpert Medical School of Brown University Pawtucket, Rhode Island Jackie P-D. Garrett, MD Clinical Assistant Professor Department of Allergy and Immunology Department of Pediatrics Tufts University School of Medicine Allergy and Immunology Associates of New England Springfield, Massachusetts Jordan F. Garris, MD Child Neurology Resident Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Estelle B. Gauda, MD Professor of Pediatrics, University of Toronto Head, Division of Neonatology

Women’s Auxiliary Chair in Neonatology at SickKids Director, Toronto Centre for Neonatal Health Senior Associate Scientist The Hospital for Sick Children Toronto, Ontario, Canada John P. Gearhart, MD Professor of Pediatric Urology The Johns Hopkins University School of Medicine Chief of Pediatric Urology The Johns Hopkins Hospital Baltimore, Maryland Jeffrey S. Gerber, MD, PhD Associate Professor of Pediatrics and Epidemiology Perelman School of Medicine at the University of Pennsylvania Division of Infectious Diseases The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Donald L. Gilbert, MD, MS, FAAN, FAAP Professor Department of Pediatrics and Neurology Program Director, Child Neurology Residency Director, Tourette Syndrome and Movement Disorders Clinics Director, Transcranial Magnetic Stimulation Laboratory Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Maureen M. Gilmore, MD Assistant Professor Department of Pediatrics The Johns Hopkins University School of Medicine Director of Neonatology Interim Chair, Pediatrics Department Johns Hopkins Bayview Medical Center Baltimore, Maryland Wendy Robin Glaberson, MD Pediatric Nephrology Fellow University of Miami Miller School of Medicine Holtz Children’s Hospital/Jackson Memorial Hospital Miami, Florida

Nicole S. Glaser, MD Professor of Pediatrics, Section of Endocrinology Dean’s Endowed Professorship for Pediatric Research University of California, Davis School of Medicine Sacramento, California Jenifer A. Glatz, MD Clinical Assistant Professor Department of Pediatrics Division of Pediatric Cardiology Children’s Hospital at Dartmouth Manchester, New Hampshire Jason F. Goldberg, MD, FAAP Assistant Professor, Pediatric Cardiomyopathy and Heart Transplantation University of Tennessee Health Sciences Center Le Bonheur Children’s Hospital St. Jude Children’s Research Hospital Memphis, Tennessee W. Christopher Golden, MD Assistant Professor of Pediatrics Division of Neonatology Director, Pediatrics Core Clerkship The Johns Hopkins University School of Medicine Neonatologist and Medical Director Newborn Nursery The Johns Hopkins Hospital Baltimore, Maryland Samuel B. Goldfarb, MD Professor of Clinical Pediatrics University of Pennsylvania Medical Director Pediatric Lung and Heart/Lung Transplant Programs Division of Pulmonary Medicine Medical Director, Solid Organ Transplant Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Mitchell Goldstein, MD, MBA Assistant Professor of Pediatrics Medical Director, Child Protection Team Johns Hopkins University

Baltimore, Maryland Stuart L. Goldstein, MD Clark D. West Endowed Chair Professor Department of Pediatrics University of Cincinnati College of Medicine Director, Center for Acute Care Nephrology Co-Director, Heart Institute Research Core Division of Nephrology and Hypertension The Heart Institute Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Kandace L. Gollomp, MD Instructor, Department of Pediatrics Attending Physician, Division of Hematology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Michelle Marie Gontasz, MD Fellow Department of Neonatology Johns Hopkins University Baltimore, Maryland Blanca E. Gonzalez, MD Assistant Professor of Pediatrics Center for Pediatric Infectious Diseases Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Pediatric Infectious Diseases Cleveland Clinic Children’s Hospital Cleveland, Ohio Zoe M. González-García, MD Assistant Professor, Pediatric Endocrinology Children’s Hospital and Medical Center University of Nebraska Medical Center Creighton University, School of Medicine Omaha, Nebraska Eliza M. Gordon-Lipkin, MD Fellow, Neurodevelopmental Disabilities Kennedy Krieger Institute

Departments of Pediatrics and Neurology The Johns Hopkins University School of Medicine Baltimore, Maryland Craig H. Gosdin, MD, MSHA Assistant Professor of Pediatrics University of Cincinnati Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Kerri Gosselin, MD, MPH Assistant Professor of Pediatrics Director, Pediatric Nutrition University of Massachusetts Medical School Worcester, Massachusetts Matthew Grady, MD, CAQSM Fellowship Director Primary Care Sports Medicine Assistant Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Pediatric and Adolescent Sports Medicine Department of Orthopedic Surgery The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Cori Green, MD, MSc Assistant Professor of Pediatrics New York-Presbyterian/Weill Cornell Medicine New York, New York Benjamin M. Greenberg, MD, MHS Associate Professor, Department of Neurology and Neurotherapeutics Associate Professor, Department of Pediatrics Vice Chair, Translational Research, Department of Neurology and Neurotherapeutics University of Texas Southwestern Dallas, Texas David C. Griffith, MD Clinical Fellow Division of Pediatric Infectious Diseases Johns Hopkins Medical Institutions Baltimore, Maryland Jennifer L. Griffith, MD, PhD

Fellow Pediatric Epilepsy Washington University in St. Louis School of Medicine St. Louis Children’s Hospital St. Louis, Missouri Adda Grimberg, MD Associate Professor Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania Scientific Director Diagnostic and Research Growth Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Andrew B. Grossman, MD Assistant Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Co-Director, Center for Pediatric Inflammatory Bowel Disease Division of Gastroenterology, Hepatology, and Nutrition The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Amit S. Grover, MB BCh BAO, MSc Instructor in Pediatrics Harvard Medical School Co-Director, Pancreatic Disorders Program Division of Gastroenterology, Hepatology, and Nutrition Boston Children’s Hospital Boston, Massachusetts Roberto Gugig, MD Associate Professor Division of Pediatric Gastroenterology Director, Endoscopy Unit Valley Children’s Hospital Lucile Packard Children’s Hospital Stanford Palo Alto, California Deepti Gupta, MD† Assistant Professor Department of Pediatrics Division of Pediatric Dermatology University of Washington School of Medicine

Seattle Children’s Hospital Seattle, Washington Kim Haberer, MD, FRCPC Fetal and Neonatal Cardiology Fellow University of Alberta Edmonton, Alberta, Canada David J. Hackam, MD, PhD, FACS Garrett Professor and Chief of Pediatric Surgery Professor of Surgery, Pediatrics and Cell Biology Johns Hopkins University School of Medicine Pediatric Surgeon in Chief and Co-Director, Johns Hopkins Children’s Center The Charlotte R. Bloomberg Children’s Center The Johns Hopkins Hospital Baltimore, Maryland Maha N. Haddad, MD† Associate Professor Department of Pediatrics University of California, Davis Director, Pediatric Dialysis UC Davis Medical Center Sacramento, California Elizabeth J. Hait, MD, MPH Assistant Professor of Pediatrics Harvard Medical School Division of Gastroenterology and Nutrition Boston Children’s Hospital Boston, Massachusetts Chad R. Haldeman-Englert, MD Clinical Geneticist Fullerton Genetics Center Asheville, North Carolina Mark E. Halstead, MD Associate Professor Department of Pediatrics and Orthopedics Washington University Director, Sports Concussion Clinic Medical Director, Young Athlete Center St. Louis Children’s Hospital

St. Louis, Missouri J. Nina Ham, MD Assistant Professor of Pediatrics Emory University School of Medicine Children’s Healthcare of Atlanta Atlanta, Georgia Ada Hamosh, MD, MPH Dr. Frank V. Sutland Professor McKusick-Nathans Institute of Genetic Medicine (IGM) Clinical Director, IGM Scientific Director, OMIM Johns Hopkins University Baltimore, Maryland Patrick C. Hanley, MD, FAAP Pediatric Endocrinology Fellow The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Brian D. Hanna, MD, PhD Clinical Professor of Pediatrics University of Pennsylvania School of Medicine Director, Section of Pulmonary Hypertension The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Cheryl A. Harrow, DNP, FNP-BC, MS, RNC-LRN, IBCLC Family Nurse Practitioner Newborn Nursery Department of Pediatrics Johns Hopkins Bayview Medical Center Baltimore, Maryland Emily A. Hartford, MD, MPH Assistant Professor, Pediatric Emergency Medicine University of Washington Seattle Children’s Hospital Seattle, Washington Brian P. Hasley, MD Associate Professor Department of Orthopedic Surgery University of Nebraska Medical Center

Children’s Hospital & Medical Center Omaha, Nebraska Caroline Hastings, MD† Clinical Professor Department of Pediatrics UCSF School of Medicine Director Pediatric Hematology/Oncology Fellowship Program Children’s Hospital & Research Center Oakland Oakland, California David Hehir, MD, MS Associate Professor of Pediatrics Thomas Jefferson University Philadelphia, Pennsylvania Chief, Cardiac Critical Care Nemours Alfred I. duPont Hospital for Children Wilmington, Delaware Michelle L. Hermiston, MD, PhD† Associate Professor Department of Pediatrics Division of Pediatric Hematology-Oncology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Christina R. Hermos, MD Assistant Professor of Pediatrics Division of Pediatric Immunology and Infectious Diseases UMass Memorial Children’s Medical Center Associate Program Director, Pediatrics Residency University of Massachusetts Medical School Worcester, Massachusetts Eugene R. Hershorin, MD Professor Department of Clinical Pediatrics Associate Chair, Department of Pediatrics Chief, Division of General Pediatrics Director, Developmental and Behavioral Pediatrics University of Miami Miller School of Medicine Miami, Florida

Kathryn L. Hillenbrand, MA, CCC-SLP Master Faculty Specialist Department of Speech, Language, and Hearing Sciences Western Michigan University Kalamazoo, Michigan Bernadette A. Hillman, MD Neonatologist Mt. Washington Pediatric Hospital Baltimore, Maryland Tanya Hinds, MD, FAAP Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Attending Pediatrician Freddie Mac Foundation Child and Adolescent Protection Center Children’s National Medical Center Washington, DC Gurumurthy Hiremath, MD, FACC, FSCAI Assistant Professor of Pediatrics Division of Pediatric Cardiology Director, Pediatric Interventional Cardiology University of Minnesota Masonic Children’s Hospital Minneapolis, Minnesota Michael P. Hirsh, MD, FACS, FAAP Professor Department of Surgery and Pediatrics University of Massachusetts Medical School Surgeon-in-Chief and Chief of Division of Pediatric Surgery UMass Memorial Children’s Medical Center Worchester, Massachusetts Adam B. Hittelman, MD, PhD, FACS† Assistant Professor Department of Urology Yale School of Medicine Pediatric Urology Department of Urology Yale–New Haven Hospital New Haven, Connecticut

Erik R. Hoefgen, MD, MS Clinical and Research Fellow Division of Hospital Medicine Department of Pediatrics Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Robert J. Hoffman, MD, MS Medical Director, Qatar Poison Center Department of Emergency Medicine, Sidra Medicine Doha Qatar Department of Emergency Medicine Mount Sinai Beth Israel New York, New York Paul L. Hofman, FRACP Professor Pediatric Endocrinology University of Auckland Director of the Paykel CRU Liggins Institute Auckland, New Zealand Kimberlee Honda, RN, MS, FNP Assistant Clinical Professor, Family Health Care Nursing University of California, San Francisco Director, Pediatric Asthma Clinic, Children’s Health Center Zuckerberg San Francisco General Hospital San Francisco, California Rachel K. Hopper, MD Clinical Assistant Professor of Pediatrics (Cardiology) Stanford University School of Medicine Associate Director, Pediatric Pulmonary Hypertension Program Lucile Packard Children’s Hospital Stanford Stanford, California Biljana N. Horn, MD Clinical Professor University of California, San Francisco Medical Director Pediatric Bone Marrow Transplant Department of Pediatrics UCSF Benioff Children’s Hospital San Francisco San Francisco, California

Arvind Hoskoppal, MD, MHS† Assistant Professor Department of Pediatrics and Internal Medicine Director, Utah Adult Congenital Heart Disease Program University of Utah and Intermountain Healthcare Salt Lake City, Utah Renee M. Howard, MD Professor of Dermatology University of California, San Francisco Director, Division of Dermatology UCSF Benioff Children’s Hospital Oakland Oakland, California Michael H. Hsieh, MD, PhD Associate Professor of Urology (Primary) and Pediatrics (Secondary) The George Washington University Children’s National Health Systems Washington, DC Benjamin J. Huang, MD Assistant Adjunct Professor of Pediatrics Division of Hematology/Oncology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California James N. Huang, MD Professor of Pediatrics University of California, San Francisco Director, Pediatric Hematology UCSF Benioff Children’s Hospital San Francisco San Francisco, California Tannie Huang, MD Kaiser Permanente Santa Clara, California Brittany B. Hubbell, MD Staff Physician, Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Jennifer Huffman, MD Pediatric Neurology

Department of Pediatrics Randall Children’s Hospital Portland, Oregon Eva C. Ihle, MD, PhD Associate Clinical Professor Department of Health Sciences University of California, San Francisco Departments of Psychiatry and Pediatrics Langley Porter Psychiatric Institute and Weill Institute for Neurosciences San Francisco, California Erik A. Imel, MD, MS Associate Professor Department of Medicine and Pediatrics Division of Endocrinology and Metabolism Indiana University School of Medicine Department of Internal Medicine and Pediatric Endocrinology/Diabetology Section Department of Pediatrics Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Rimsha Iqbal, MD Pediatric Resident Beaumont Children’s Hospital Royal Oak, Michigan Allison M. Jackson, MD, MPH Associate Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Division Chief, Child and Adolescent Protection Center Children’s National Health System Washington Children’s Foundation Professor of Child and Adolescent Protection Washington, DC Oksana A. Jackson, MD Assistant Professor, Division of Plastic Surgery Co-Director, Cleft Lip and Palate Program Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Shonul A. Jain, MD Associate Professor

Department of Pediatrics University of California, San Francisco Vice-Chief, Department of Pediatrics Medical Director, Children’s Health Center Zuckerberg San Francisco General Hospital San Francisco, California Maria Jacklin Janecek, DO† General Pediatrician Downers Grove Pediatrics Downers Grove, Illinois Karen E. Jerardi, MD, MEd Assistant Professor Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Chandy C. John, MD, MS Ryan White Professor of Pediatrics Professor of Medicine, Microbiology, and Immunology Director, Ryan White Center for Pediatric Infectious Diseases and Global Health Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Julia Johnson, MD Assistant Professor of Pediatrics Division of Neonatology Johns Hopkins University Baltimore, Maryland Ray J. Jurado, DDS Division Head, Dentistry Ann & Robert H. Lurie Children’s Hospital of Chicago Program Director, Pediatric Dentistry Northwestern University Feinberg School of Medicine Chicago, Illinois Dylan C. Kann, MD Pediatric Infectious Diseases Department of Pediatric Subspecialties Kaiser Permanente Santa Clara Medical Center Santa Clara, California

Chirag R. Kapadia, MD Associate Professor of Pediatrics University of Arizona College of Medicine-Phoenix Fellowship Program Director Division Chief, Pediatric Endocrinology Phoenix Children’s Hospital Phoenix, Arizona Laura E. Kaplan, BA Medical Student SUNY Downstate Medical Center College of Medicine Brooklyn, New York Wikrom Karnsakul, MD Associate Professor Department of Pediatrics The Johns Hopkins University School of Medicine Pediatric Liver Center Baltimore, Maryland Judith Kelsen, MD Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Director of the Very Early Onset Inflammatory Bowel Disease Program Division of Gastroenterology, Hepatology, and Nutrition The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Shellie M. Kendall, MD† Assistant Professor Department of Pediatrics Uniformed Services University of the Health Sciences Bethesda, Maryland Director, Division of Pediatric Cardiology Naval Medical Center San Diego San Diego, California Sadiqa Kendi, MD, FAAP Attending Physician, Pediatric Emergency Medicine Children’s National Health System Washington, DC Kalpashri Kesavan, MD Assistant Professor of Pediatrics

University of California, Los Angeles David Geffen School of Medicine Los Angeles, California Seema Khan, MD Associate Professor of Pediatrics Division of Gastroenterology, Hepatology & Nutrition Children’s National Medical Centre George Washington University School of Medicine & Health Sciences Washington, DC Amer M. Khojah, MD Allergy Immunology and Pediatric Rheumatology Fellow Ann & Robert H. Lurie Children’s Hospital of Chicago Northwestern University Chicago, Illinois Jessica M. Khouri, MD Senior Medical Officer Infant Botulism Treatment and Prevention Program California Department of Public Health Richmond, California Nadine M. Khouzam, MD Assistant Professor of Clinical Pediatrics Keck School of Medicine of USC Pediatric Nephrologist Children’s Hospital Los Angeles Los Angeles, California Harry K.W. Kim, MD Professor of Orthopedic Surgery University of Texas Southwestern Medical Center Director of Research Director, Center for Excellence in Hip Disorders Texas Scottish Rite Hospital for Children Dallas, Texas Sivan Kinberg, MD, MS, MA Assistant Professor Department of Pediatrics Columbia University Medical Center Director, Pediatric Intestinal Rehabilitation Clinic Division of Pediatric Gastroenterology, Hepatology, and Nutrition

New York, New York Terry Kind, MD, MPH Associate Professor Department of Pediatrics Assistant Dean for Clinical Education The George Washington University School of Medicine & Health Sciences Children’s National Health System Washington, DC Eric S. Kirkendall, MD, MBI, FAAP Associate Professor of Clinical Pediatrics, Division of Hospital Medicine University of Cincinnati Associate Chief Medical Information Officer Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Shyam Kishan, MD Associate Professor Indiana University Pediatric Orthopedics and Scoliosis Surgery Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Eimear Kitt, MB, BCh, BAO (NUI) Fellow Physician Division of Infectious Diseases The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Kirsten M. Kloepfer, MD, MS Assistant Professor Department of Pediatrics Section of Pulmonary, Allergy, and Sleep Medicine Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Kelly G. Knupp, MD, MSCS Associate Professor of Pediatrics and Neurology University of Colorado Denver, Anschutz Medical Campus Children’s Hospital Colorado Aurora, Colorado Aaron E. Kornblith, MD

Assistant Professor Department of Emergency Medicine and Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Sarah A. Korth, MD Pediatric Rehabilitation Medicine Co-Director, Keelty Center for Spina Bifida and Related Conditions Kennedy Krieger Institute Johns Hopkins University Baltimore, Maryland Renee K. Kottenhahn, MD Clinical Associate Professor of Pediatrics Department of Pediatrics Drexel University College of Medicine Attending Physician General Pediatrics and Adolescent Medicine St. Christopher’s Hospital for Children Philadelphia, Pennsylvania Courtney L. Kraus, MD Assistant Professor Department of Ophthalmology Pediatric Ophthalmology and Adult Strabismus Krieger Children’s Eye Center Wilmer Eye Institute Baltimore, Maryland Richard M. Kravitz, MD Professor Department of Pediatrics Duke University Medical Center Director, Pediatric Sleep Lab Co-Director, Duke Children’s Neuromuscular Program Durham, North Carolina Preetha Krishnan, MD Clinical Director of Pediatric Neurocritical Care Attending Physician, Pediatric Critical Care Medicine Randall Children’s Hospital at Legacy Emanuel Portland, Oregon Matthew P. Kronman, MD, MSCE

Associate Professor Department of Pediatrics University of Washington Director, Pediatric Infectious Diseases Fellowship Training Program Department of Pediatrics Division of Infectious Diseases Seattle Children’s Hospital Seattle, Washington Elaine Ku, MD, MAS Assistant Professor Divisions of Nephrology and Pediatric Nephrology University of California, San Francisco San Francisco, California Johnny I. Kuttab, DDS Diplomate of the American Board of Pediatric Dentistry Fellow of the American Academy of Pediatric Dentistry Ann & Robert H. Lurie Children’s Hospital of Chicago Advocate Lutheran General Hospital Chicago, Illinois A. Desiree LaBeaud, MD, MS Associate Professor Department of Pediatrics (Infectious Diseases) and Health Research and Policy Stanford University Stanford, California Mitchell R. Ladd, MD, PhD General Surgery Resident Department of Surgery The Johns Hopkins Hospital Baltimore, Maryland Meredith C. Laguna, MD, MPH Clinical Instructor Department of Pediatrics Division of General Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Michele Puszkarczuk Lambert, MD, MSTR Associate Professor

Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Judith Brylinski Larkin, MD, FAAP Clinical Assistant Professor Department of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University Nemours duPont Pediatrics, Philadelphia Philadelphia, Pennsylvania Javier J. Lasa, MD, FAAP Assistant Professor Department of Pediatrics Divisions of Critical Care Medicine and Cardiology Baylor College of Medicine Texas Children’s Hospital Houston, Texas Phuoc V. Le, MD, MPH, DTM&H Associate Professor, Internal Medicine and Pediatrics Co-Founder, HEAL Initiative University of California, San Francisco San Francisco, California Howard M. Lederman, MD, PhD Professor of Pediatrics, Medicine, and Pathology The Johns Hopkins University School of Medicine Director, Immune Deficiency Clinic Pediatrics The Johns Hopkins Hospital Baltimore, Maryland Christine K. Lee, MD Instructor Department of Pediatrics Harvard Medical School Attending Physician Division of Gastroenterology, Hepatology, and Nutrition Boston Children’s Hospital Boston, Massachusetts Marsha May Lee, MD

Assistant Clinical Professor of Pediatrics, Pediatric Nephrology University of California, San Francisco Medical Director, Pediatric Dialysis Unit UCSF Benioff Children’s Hospital San Francisco San Francisco, California Sarah Lee, MD Clinical Assistant Professor Department of Neurology and Neurological Sciences Director, Pediatric Stroke Program at Stanford Stanford Stroke Center/Stanford Children’s Health Palo Alto, California Kevin V. Lemley, MD, PhD Professor Department of Pediatrics Keck School of Medicine of USC Attending Nephrologist Children’s Hospital of Los Angeles Los Angeles, California Kieran Leong, DO Pediatric Cardiology Fellow Division of Pediatric Cardiology University of Minnesota University of Minnesota Masonic Children’s Hospital Minneapolis, Minnesota Eric B. Levey, MD Chief Medical Officer Health Services for Children with Special Needs Washington, DC Adjunct Associate Professor Johns Hopkins University School of Medicine Baltimore, Maryland Daniel E. Levin, MD Pediatric Surgical Fellow Johns Hopkins Children’s Center Baltimore, Maryland Leonard J. Levine, MD Associate Professor of Pediatrics Assistant Dean for Student Affairs

Drexel University College of Medicine Attending Physician, Division of Adolescent Medicine St. Christopher’s Hospital for Children Philadelphia, Pennsylvania Walter L. Li, MD† Assistant Clinical Professor Department of Pediatrics Division of Cardiology and Electrophysiology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco & Modesto Satellite Clinic San Francisco, California Cara Lichtenstein, MD, MPH Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Attending Pediatrician General and Community Pediatrics Children’s National Medical Center Washington, DC Tiffany F. Lin, MD Adjunct Instructor Department of Pediatrics, Division of Pediatric Hematology/Oncology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Paul H. Lipkin, MD Associate Professor of Pediatrics The Johns Hopkins University School of Medicine Director, Medical Informatics and the Interactive Autism Network Kennedy Krieger Institute Baltimore, Maryland Richard A. Lirio, MD† Assistant Professor Department of Pediatrics University of Massachusetts Medical School Director, Pediatric Endoscopy UMass Memorial Children’s Medical Center Worcester, Massachusetts

Robert Listernick, MD Professor Department of Pediatrics Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Division of Academic General Pediatrics Chicago, Illinois Jessica R. Litwin, MD Assistant Clinical Professor of Child Neurology UCSF School of Medicine Pediatric Neurologist UCSF Benioff Children’s Hospital San Francisco San Francisco, California Warren D. Lo, MD Clinical Professor of Pediatrics and Neurology The Ohio State University Nationwide Children’s Hospital Columbus, Ohio Maya B. Lodish, MD, MHSCR Associate Research Physician Program Director, Fellowship in Pediatric Endocrinology National Institute of Child Health and Human Development Bethesda, Maryland Kelsey Logan, MD, MPH Associate Professor of Pediatrics and Internal Medicine University of Cincinnati College of Medicine Director, Division of Sports Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Allison R. Loh, MD Assistant Professor Department of Pediatric Ophthalmology and Strabismus Casey Eye Institute Oregon Health & Science University Portland, Oregon Melissa Long, MD Assistant Professor Department of Pediatrics

The George Washington University School of Medicine & Health Sciences Attending Physician Children’s National Medical Center Washington, DC Sahira A. Long, MD, IBCLC, FABM Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Medical Director, Children’s Health Centers-Anacostia Children’s National Health System Washington, DC Kathleen M. Loomes, MD Associate Professor Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania Division of Gastroenterology, Hepatology, and Nutrition The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Katherine Lord, MD Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Alexander Lowenthal, MD Pediatric Cardiologist Department of Pediatric Cardiology Schneider Children’s Medical Center of Israel Petach Tikvah, Israel Jeffrey R. Lukish, MD, FACS Associate Professor Department of Surgery The Johns Hopkins University School of Medicine Baltimore, Maryland Sarah S. Lusman, MD, PhD Assistant Professor Department of Pediatrics Columbia University Medical Center Director, Pediatric Gastroenterology Fellowship Training Program

Associate Director, Pediatric Residency Program Division of Pediatric Gastroenterology, Hepatology, and Nutrition Morgan Stanley Children’s Hospital of New York-Presbyterian New York, New York Minnelly Luu, MD Assistant Professor Department of Dermatology Keck School of Medicine of USC Director, Pediatric Dermatology Children’s Hospital Los Angeles Los Angeles, California Ngoc P. Ly, MD, MPH Professor of Pediatrics Chief, Division of Pediatric Pulmonology, Cystic Fibrosis and Sleep Medicine University of California, San Francisco (UCSF) University of California, San Francisco UCSF Benioff Children’s Hospitals, Oakland and San Francisco San Francisco, California Sheela N. Magge, MD, MSCE Assistant Professor of Pediatrics Department of Pediatrics The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Melanie M. Makhija, MD, MSc Assistant Professor Department of Pediatrics Northwestern University Feinberg School of Medicine Attending Physician Division of Allergy and Immunology Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Michael A. Manfredi, MD Assistant Professor of Pediatrics Harvard Medical School Medical Director Esophageal and Airway Treatment Center Attending Physician, Gastroenterology and Nutrition Boston Children’s Hospital Boston, Massachusetts

Courtney W. Mangus, MD Pediatric Emergency Medicine Fellow Johns Hopkins Children’s Center Baltimore, Maryland Melissa L. Mannion, MD, MSPH Assistant Professor of Pediatrics, Pediatric Rheumatology The University of Alabama at Birmingham Birmingham, Alabama Fiona Marion, MB, BCh, BAO Primary Pediatric Medical Group Alameda, California Andrea Marmor, MD, MSEd Professor of Pediatrics University of California, San Francisco Zuckerberg San Francisco General Hospital San Francisco, California Anne M. Marsh, MD Associate Hematologist/Oncologist Director, Pediatric Sickle Cell Clinic UCSF Benioff Children’s Hospital Oakland Oakland, California Holly H. Martin, MD Assistant Professor Department of Pediatrics University of California, San Francisco Zuckerberg San Francisco General Hospital San Francisco, California Zankhana Master, MD† Assistant Professor Department of Child Health Department of Pediatrics Division of Neonatology University of Missouri Columbia, Missouri Lucy D. Mastrandrea, MD, PhD Associate Professor Department of Pediatrics Jacobs School of Medicine and Biomedical Sciences

University at Buffalo Associate Division Chief Pediatric Endocrinology Women and Children’s Hospital of Buffalo Buffalo, New York Carol A. Mathews, MD Brooke Professor of Psychiatry Director Center for OCD, Anxiety, & Related Disorders University of Florida Gainesville, Florida Anubhav Mathur, MD, PhD Assistant Professor of Dermatology, Pediatric Division University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Alison T. Matsunaga, MD Medical Director General Hematology Program, Hemophilia, and Thrombosis Center UCSF Benioff Children’s Hospital Oakland Oakland, California Lindsay J. May, MD, FRCPC Assistant Professor Pediatrics University of Utah Pediatric Cardiology, Heart Failure, and Transplantation Primary Children’s Hospital Salt Lake City, Utah Oscar Henry Mayer, MD Associate Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Medical Director, Pulmonary Function Testing Laboratory Division of Pulmonary Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Shana E. McCormack, MD, MTR Attending Physician Division of Endocrinology and Diabetes The Children’s Hospital of Philadelphia

Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania Donna M. McDonald-McGinn, MS, LCGC Clinical Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Chief, Section of Genetic Counseling Director, 22q and You Center Associate Director, Clinical Genetics Center The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Tracey A. McLean, MD Obstetrics and Gynecology Kaiser Permanente Livermore, California Robert J. McLoughlin, MD Department of General Surgery University of Massachusetts Medical School Worcester, Massachusetts Maureen C. McMahon, MD Nemours Pediatrics Villanova Villanova, Pennsylvania Assistant Professor of Pediatrics Sidney Kimmel Medical College of Thomas Jefferson University Philadelphia, Pennsylvania Margaret M. McNamara, MD Professor Department of Pediatrics University of California San Francisco Associate Program Director Mentoring and Career Development, UCSF Pediatric Residency Program Co-Director, Foundations of Patient Care and Preceptorships Site Director, UCSF Bridges Curriculum CMC Zuckerberg San Francisco General Hospital San Francisco, California Maireade E. McSweeney, MD, MPH Instructor Department of Pediatrics

Harvard Medical School Attending Physician Division of Gastroenterology, Hepatology, and Nutrition Boston Children’s Hospital Boston, Massachusetts Jay Mehta, MD, MS Clinical Director, Pediatric Rheumatology The Children’s Hospital of Philadelphia Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania Jondavid Menteer, MD Associate Professor Department of Clinical Pediatrics Keck School of Medicine of USC Director, Heart Failure Program Children’s Hospital Los Angeles Los Angeles, California Laura Mercer-Rosa, MD, MSCE Assistant Professor of Pediatrics Director, Echolab Research Unit Perelman School of Medicine, University of Pennsylvania Division of Cardiology Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Michele Mietus-Snyder, MD Associate Professor Department of Pediatrics The George Washington University Co-Director Children’s National Obesity Institute Center for Translational Science Children’s National Health System Washington, DC Jennifer J. Miller, MD Neonatology Fellow Department of Pediatrics The Charlotte R. Bloomberg Children’s Center The Johns Hopkins Hospital Baltimore, Maryland

Jane E. Minturn, MD, PhD† Associate Professor Department of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Division of Oncology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Hussnain S. Mirza, MD, FAAP Assistant Professor of Pediatrics University of Central Florida College of Medicine Attending Neonatologist Center for Neonatal Care Florida Hospital for Children Orlando, Florida Nazrat Mirza, MD, ScD Associate Professor of Pediatrics George Washington University Medical Director I.D.E.A.L Pediatric Weight Management Clinic Children’s National Health System Washington, DC Douglas B. Mogul, MD, MPH Assistant Professor Pediatric Gastroenterology, Hepatology, and Nutrition The Johns Hopkins University School of Medicine Baltimore, Maryland Angela P. Mojica, MD Assistant Professor Department of Pediatrics State University of New York Attending Physician Pediatric Endocrinologist Upstate University Hospital Joslin Diabetes Center Syracuse, New York Kimberly M. Molina, MD Assistant Professor of Pediatrics Medical Director of Heart Transplant University of Utah

Primary Children’s Hospital Salt Lake City, Utah Bradley J. Monash, MD Associate Professor, Internal Medicine & Pediatrics Associate Chief, Medicine Service University of California, San Francisco San Francisco, California Amaran Moodley, MD Head Department of Pediatrics Division of Infectious Diseases Blank Children’s Hospital Des Moines, Iowa Rachel Y. Moon, MD Professor Department of Pediatrics Division Head General Pediatrics University of Virginia School of Medicine Charlottesville, Virginia Craig Munns, FRACP, MBBS, PhD Associate Professor Department of Pediatric Endocrinology University of Sydney Director, Division of Diagnostic Services The Children’s Hospital at Westmead Sydney, Australia Trish Murphy, RN, MSN Nurse Coordinator Survivors Program, Hematology/Oncology/Bone Marrow Transplant UCSF Benioff Children’s Hospital San Francisco/Oakland San Francisco, California John R. Mytinger, MD Assistant Professor Department of Pediatrics Division of Pediatric Neurology Ohio State University Nationwide Children’s Hospital

Columbus, Ohio Zeina M. Nabhan, MD Associate Professor of Clinical Pediatrics Associate Program Director of Pediatric Residency Indiana University School of Medicine Riley Hospital for Children Indianapolis, Indiana Frances M. Nadel, MD, MSCE Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Attending Physician Division of Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Jessica Rose Nance, MS, MD Assistant Professor Division of Pediatric Neurology The Johns Hopkins Hospital Baltimore, Maryland Bhavana Narala, MD Pediatric Endocrinology Fellow Medical College of Wisconsin Children’s Hospital of Wisconsin Milwaukee Milwaukee, Wisconsin Jessica E. Nash, MD Assistant Professor Department of Pediatrics The George Washington University General Pediatrician Children’s National Medical Center Washington, DC Luz Natal-Hernandez, MD Pediatric Cardiologist The Permanente Medical Group Kaiser Permanente Roseville Medical Center Roseville, California Hythem M. Nawaytou, MBBCh, MSc Assistant Professor of Pediatrics

Division of Cardiology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Pradeep P. Nazarey, MD Assistant Professor of Pediatrics and Surgery Division of Pediatric Surgery University of Massachusetts Medical School UMass Memorial Healthcare Boston, Massachusetts Todd D. Nebesio, MD, FAAP Associate Professor Department of Clinical Pediatrics Section of Pediatric Endocrinology/Diabetology Indiana University School of Medicine Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Daniel Newman, MD Assistant Clinical Professor Department of Pediatrics Children’s Health Centers, Northwest Children’s National Health System Washington, DC Jessica R. Newman, DO Assistant Professor Department of Internal Medicine Division of Infectious Diseases University of Kansas Medical Center Kansas City, Kansas Ross Newman, DO, MHPE Associate Professor of Pediatrics University of Missouri-Kansas City School of Medicine Division of General Academic Pediatrics Children’s Mercy, Kansas City Kansas City, Missouri Stephanie Nguyen, MD, MAS† Associate Professor Department of Pediatrics

Division of Nephrology University of California, Davis UC Davis Medical Center Sacramento, California Graeme A.M. Nimmo, MBBS, MSc Medical Genetics Resident The Hospital for Sick Children University of Toronto Toronto, Ontario, Canada Julie M. Nogee, MD Instructor of Pediatrics Department of Pediatrics Division of Newborn Medicine Washington University School of Medicine St. Louis, Missouri Lawrence M. Nogee, MD Professor of Pediatrics Department of Pediatrics Eudowood Neonatal Pulmonary Division The Johns Hopkins University School of Medicine Baltimore, Maryland Frances J. Northington, MD Professor of Pediatrics Director, Neurosciences Intensive Care Nursery Program The Johns Hopkins University School of Medicine Charlotte Bloomberg Children’s Center Baltimore, Maryland Adam L. Numis, MD Assistant Professor of Neurology & Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Christopher B. Oakley, MD† Assistant Professor Department of Neurology and Nursing The Johns Hopkins University School of Medicine Director, Pediatric Headache Center Director, Headache Medicine Fellowship

Associate Director Neurology Clerkship The Johns Hopkins Hospital Baltimore, Maryland D. David O’Banion, MD† Assistant Professor Department of Pediatrics Emory University School of Medicine Atlanta, Georgia Julie S. O’Brien, MD, MS Assistant Clinical Professor Department of Pediatrics University of California, San Francisco Medical Director, Pediatric Primary Care UCSF Benioff Children’s Hospital San Francisco San Francisco, California Sina Ogholikhan, MD Pediatric Gastroenterology Nemours Children’s Specialty Jacksonville, Florida Kent R. Olson, MD Clinical Professor Department of Medicine, Pharmacy, and Pediatrics University of California, San Francisco Co-Medical Director San Francisco Division California Poison Control System San Francisco, California Bruce A. Ong, LTC, MC, MD, MPH, USA† Deputy Chief of Pediatrics Department of Pediatrics Division of Pediatric Pulmonology Tripler Army Medical Center Honolulu, Hawaii Katharine A. Osborn, MD Pediatric Emergency Medicine Fellow UCSF Benioff Children’s Hospitals Oakland and San Francisco Oakland, California

Peter T. Osgood, MD Clinical Fellow in Pediatric Gastroenterology, Hepatology, and Nutrition Texas Children’s Hospital & Baylor College of Medicine Houston, Texas Kevin C. Osterhoudt, MD, MS† Professor Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania Director Section of Clinical Toxicology Division of Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Mary C. Ottolini, MD, MPH, Med Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Vice-Chair of Education and DIO Children’s National Medical Center Washington, DC Vikash S. Oza, MD Assistant Professor of Dermatology and Pediatrics Director of Pediatric Dermatology The Ronald O. Perelman Deparment of Dermatology New York University School of Medicine New York, New York Erica S. Pan, MD, MPH, FAAP Director, Division of Communicable Disease Control and Prevention (DCDCP) Deputy Health Officer Alameda County Public Health Department Clinical Professor Pediatric Infectious Diseases University of California, San Francisco UCSF Benioff Children’s Hospitals San Francisco & Oakland Oakland, California Rita Panoscha, MD Associate Professor Department of Pediatrics Institute on Development and Disabilities Oregon Health & Sciences University

Portland, Oregon Carolyn A. Paris, MD, MPH Associate Professor of Pediatrics University of Washington School of Medicine Attending Physician Division of Emergency Medicine Seattle Children’s Hospital Seattle, Washington Kristen Park, MD Associate Professor of Pediatrics and Neurology Epilepsy Fellowship Program Director University of Colorado School of Medicine Aurora, Colorado Michelle W. Parker, MD Assistant Professor Department of Pediatrics University of Cincinnati Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Akash R. Patel, MD, CEPS, FHRS† Assistant Professor Department of Pediatrics University of California, San Francisco Electrophysiologist, Pediatric and Congenital Arrhythmia Center UCSF Benioff Children’s Hospital San Francisco San Francisco, California Shreena Patel, MD Department of Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Texas Children’s Hospital Houston, Texas Irina B. Pateva, MD Assistant Professor Department of Pediatrics Case Western Reserve University Pediatric Hematology/Oncology Rainbow Babies & Children’s Hospital

Angie Fowler AYA Cancer Institute Cleveland, Ohio Barry J. Pelz, MD Assistant Professor Division of Allergy and Immunology Medical College of Wisconsin Children’s Hospital of Wisconsin Milwaukee, Wisconsin Cheryl A. C. Peretz, MD Pediatric Hematology/Oncology Fellow UCSF Benioff Children’s Hospital Oakland Oakland, California Elena E. Perez, MD, PhD Allergy Associates of the Palm Beaches North Palm Beach, Florida Jessica L. Perniciaro, MD Clinical Instructor Department of Pediatrics Keck School of Medicine of USC Fellow Division of Emergency Medicine Children’s Hospital Los Angeles Los Angeles, California Farzana Perwad, MD Assistant Professor of Pediatrics University of California, San Francisco Chief, Division of Pediatric Nephrology UCSF Benioff Children’s Hospital San Francisco San Francisco, California Shabnam Peyvandi, MD Assistant Professor of Pediatrics Division of Pediatric Cardiology UCSF Benioff Children’s Hospital San Francisco San Francisco, California Joseph A. Picoraro, MD Assistant Professor Department of Pediatrics Pediatric Gastroenterology, Hepatology, and Nutrition

Columbia University Medical Center Morgan Stanley Children’s Hospital of New York-Presbyterian New York, New York Jose A. Pineda, MD, MSCI Associate Professor Washington University School of Medicine Department of Pediatrics and Neurology Director, Neurocritical Care Program Division of Critical Care Medicine St. Louis Children’s Hospital St. Louis, Missouri Jonathan R. Pletcher, MD Director, Medical Services University Health Services Princeton University Princeton, New Jersey Charles A. Pohl, MD Professor Department of Pediatrics Vice Dean of Student Affairs Sidney Kimmel Medical College of Thomas Jefferson University Vice Provost of Student Affairs Thomas Jefferson University Philadelphia, Pennsylvania Evelyn Porter, MD, MS Assistant Professor Departments of Emergency Medicine and Pediatrics University of California, San Francisco Medical Center at Parnassus Heights UCSF Benioff Children’s Hospital San Francisco, California Anthony F. Porto, MD, MPH† Assistant Professor Department of Pediatrics Yale University Associate Clinical Chief, Pediatric Gastroenterology Director, Pediatric Gastroenterology Greenwich Hospital New Haven, Connecticut

Amanda Posner, MD Fellow Department of Pediatric Gastroenterology UCSF Benioff Children’s Hospital San Francisco San Francisco, California Madhura Pradhan, MD Associate Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Victoria E. Price, MBChB, MSc, FRCPC† Associate Professor Department of Pediatrics Division of Pediatric Hematology/Oncology IWK Health Centre Dalhousie University Halifax, Nova Scotia, Canada Benjamin T. Prince, MD, MSci† Assistant Professor Department of Pediatrics, Allergy & Immunology The Ohio State University College of Medicine Nationwide Children’s Hospital Columbus, Ohio Manisha Punwani, MD Director, Child and Adolescent Psychiatry Training Associate Professor Department of Psychiatry University of California, San Francisco San Francisco, California Kendall Purcell, MD, MPH† Assistant Professor Department of Pediatrics University of Louisville Louisville, Kentucky Katherine B. Püttgen, MD Assistant Professor Department of Dermatology and Pediatrics Director, Division of Pediatric Dermatology

The Johns Hopkins University School of Medicine Baltimore, Maryland Nashmia Qamar, DO, MSc Assistant Professor Department of Pediatrics Division of Allergy & Immunology Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Karen A. Queliza, MD Clinical Fellow Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Texas Children’s Hospital Houston, Texas Luis H. Quiroga, MD Burn & Reconstructive Surgery Fellow Department of Plastic & Reconstructive Surgery The Johns Hopkins University School of Medicine Baltimore, Maryland Christopher P. Raab, MD Assistant Professor Pediatrics Sidney Kimmel College of Medicine Thomas Jefferson University Staff Pediatrician Nemours/A.I. duPont Hospital for Children Philadelphia, Pennsylvania Mary Scott Ramnitz, MD Pediatric Endocrinologist Section on Skeletal Disorders and Mineral Homeostasis National Institute of Dental and Craniofacial Research/National Institutes of Health Bethesda, Maryland Daniel Ranch, MD Assistant Professor Department of Pediatrics Division of Pediatric Nephrology University of Texas Health Science Center, San Antonio San Antonio, Texas

Vamshi K. Rao, MD Assistant Professor Northwestern University Feinberg School of Medicine Attending Physician Division of Neurology Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Robert I. Raphael, MD Associate Director Survivors of Childhood Cancer Program UCSF Benioff Children’s Hospital Oakland Oakland, California Sergio E. Recuenco, MD, MPH, DrPH† Professor Department of Epidemiology Universidad Nacional Mayor de San Marcos (UNMSM) Senior Researcher Department of Preventive Medicine and Public Health Center for Technological, Biomedical, and Environmental Research Faculty of Medicine UNMSM Daniel A. Carrion Tropical Medicine Institute Lima, Peru Richard J. Redett, MD Professor Plastic and Reconstructive Surgery The Johns Hopkins University School of Medicine Director Pediatric Plastic Surgery The Charlotte R. Bloomberg Children’s Center Baltimore, Maryland Rebecca Reindel, MD Silver Spring, Maryland Michael X. Repka, MD, MBA Professor of Pediatrics The David L. Guyton, MD and Feduniak Family Professor of Ophthalmology The Johns Hopkins University School of Medicine Baltimore, Maryland Leah G. Reznick, MD

Associate Professor Department of Ophthalmology Casey Eye Institute Oregon Health & Sciences University Portland, Oregon Hope E. Rhodes, MD, MPH, FAAP Assistant Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Co-Medical Director Healthy Generations Program Children’s National Medical Center Washington, DC Richard C. Rink, MD Robert A. Garrett Professor of Pediatric Urologic Research Professor Department of Urology Indiana University School of Medicine Indianapolis, Indiana Elizabeth Robbins, MD Clinical Professor Department of Pediatrics, Hematology/Oncology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Shenandoah Robinson, MD Professor Neurosurgery, Neurology, and Pediatrics Johns Hopkins University Johns Hopkins Children’s Center Baltimore, Maryland Rachel G. Robison, MD Assistant Professor Department of Pediatrics Northwestern University Feinberg School of Medicine Attending Physician Pediatrics, Division of Allergy & Immunology Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois

Stephen M. Rosenthal, MD Professor of Pediatrics Division of Pediatric Endocrinology University of California, San Francisco Medical Director, Child and Adolescent Gender Center Mission Hall: Global Health and Clinical Sciences San Francisco, California Tamanna R. Roshan Lal, MBChB Clinical Genetics Chief Resident The Johns Hopkins University School of Medicine Institute of Genetic Medicine Baltimore, Maryland Rebecca L. Ruebner, MD, MSCE Assistant Professor Department of Pediatrics Division of Pediatric Nephrology The Johns Hopkins University School of Medicine Baltimore, Maryland Eric T. Rush, MD, FAAP, FACMG Associate Professor of Pediatrics University of Missouri - Kansas City Clinical Geneticist Children’s Mercy Hospital Kansas City, Missouri Thomas G. Saba, MD Assistant Professor Department of Pediatrics and Communicable Diseases Pulmonary Division University of Michigan C.S. Mott Children’s Hospital Ann Arbor, Michigan Camille Sabella, MD Associate Professor of Pediatrics Vice-Chair for Education, Pediatric Institute Director, Center for Pediatric Infectious Diseases Cleveland Clinic Children’s Hospital Cleveland, Ohio Amit J. Sabnis, MD Assistant Professor, Pediatric Hematology-Oncology

University of California, San Francisco (UCSF) UCSF Benioff Children’s Hospital San Francisco San Francisco, California Nina N. Sainath, MD Pediatric Gastroenterology & Nutrition Fellow The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Amin Salem, MD, MRCPCH, DCH, DPP Assistant Professor of Clinical Pediatrics Weill Cornell Medical College Qatar Senior Attending Physician Pediatric Emergency Department Sidra Medicine Doha, Qatar Denise A. Salerno, MD Professor of Clinical Pediatrics Department of Pediatrics Temple University School of Medicine Philadelphia, Pennsylvania Lauren A. Sanchez, MD Clinical Fellow, Pediatric Allergy, Immunology, and BMT University of California, San Francisco San Francisco, California Pablo J. Sánchez, MD Professor of Pediatrics Divisions of Neonatal-Perinatal Medicine and Pediatric Infectious Diseases The Ohio State University College of Medicine, Nationwide Children’s Hospital The Research Institute at Nationwide Children’s Hospital Center for Perinatal Research Columbus, Ohio Melissa T. Sanford, MD Resident Physician Department of Urology University of California, San Francisco San Francisco, California Kara N. Saperston, MD Staff Pediatric Urologist St Luke’s Children’s Hospital

Boise, Idaho Matthew R. Schefft, DO, MSHA Assistant Professor Department of Pediatrics Division of Hospital Medicine Children’s Hospital of Richmond at Virginia Commonwealth University Richmond, Virginia Adrienne M. Scheich, MD Attending Physician Division of Gastroenterology, Hepatology, and Nutrition Ann & Robert H. Lurie Children’s Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago, Illinois Rebecca Schein, MD Assistant Professor of Pediatrics and Human Development College of Human Medicine Michigan State University East Lansing, Michigan Angela E. Scheuerle, MD Professor Department of Pediatrics Division of Genetics and Metabolism University of Texas Southwestern Medical Center Dallas, Texas Jocelyn Huang Schiller, MD Clinical Associate Professor of Pediatrics University of Michigan Medical School C.S. Mott Children’s Hospital Ann Arbor, Michigan Melissa Schoelwer, MD Assistant Professor Department of Pediatrics, Endocrinology University of Virginia Children’s Hospital Charlottesville, Virginia Amanda C. Schondelmeyer, MD, MSc Assistant Professor of Pediatrics University of Cincinnati Attending Physician Hospital Medicine

Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Alan R. Schroeder, MD Clinical Professor of Pediatrics (Hospital Medicine and Critical Care) Stanford University School of Medicine Associate Chief for Research Division of Hospital Medicine Lucile Packard Children’s Hospital Stanford Palo Alto, California Steven M. Selbst, MD Professor of Pediatrics Director, Pediatric Residency Program Sidney Kimmel Medical College at Thomas Jefferson University Philadelphia, Pennsylvania Attending Physician Division of Emergency Medicine Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware Mamata V. Senthil, MD Fellow Physician Division of Pediatric Emergency Medicine The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Samir S. Shah, MD, MSCE Professor, Department of Pediatrics University of Cincinnati College of Medicine Director, Division of Hospital Medicine James M. Ewell Endowed Chair Attending Physician, Infectious Diseases and Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Sonal D. Shah, MD Assistant Clinical Professor Dermatology & Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Pareen Shah Thakral, MD

Attending Physician, General Pediatrics Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Hemant P. Sharma, MD, MS, MHS Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Clinical Chief, Division of Allergy and Immunology Children’s National Medical Center Washington, DC Helen M. Sharp, PhD Professor and Director School of Communication Sciences and Disorders Pacific University Forest Grove, Oregon Erin E. Shaughnessy, MD, MSHCM Associate Professor of Child Health University of Arizona College of Medicine Phoenix Chief, Division of Hospital Medicine Phoenix Children’s Hospital Phoenix, Arizona Jeanne S. Sheffield, MD Professor of Gynecology and Obstetrics Division Director, Maternal-Fetal Medicine The Johns Hopkins University School of Medicine Baltimore, Maryland T. Matthew Shields, MD Assistant Professor of Pediatrics Division of Pediatric Gastroenterology UMass Memorial Medical Center Worcester, Massachusetts Kristin A. Shimano, MD HS Associate Clinical Professor Pediatric Hematology/Oncology and Bone Marrow Transplant UCSF Benioff Children’s Hospital San Francisco San Francisco, California Timothy R. Shope, MD, MPH Associate Professor

Department of Pediatrics Division of General Academic Pediatrics Children’s Hospital of Pittsburgh University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Stanford T. Shulman, MD Professor of Pediatrics Division of Infectious Diseases Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Anna Sick-Samuels, MD, MPH Pediatric Infectious Diseases Clinical and Research Fellow The Johns Hopkins University School of Medicine Johns Hopkins Children’s Center Baltimore, Maryland Melissa A. Simon, MD Clinical Assistant Professor Department of Ophthalmology Brown University Department of Surgery Rhode Island Hospital Providence, Rhode Island Anne Marie Singh, MD Assistant Professor Departments of Pediatrics-Allergy and Immunology, Medicine-Allergy-Immunology Northwestern University Feinberg School of Medicine Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, Illinois Arunjot Singh, MD, MPH Assistant Professor Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Michael J. Smith, MD, MSCE Associate Professor of Pediatrics Division of Pediatric Infectious Diseases

Duke University Medical Center Durham, North Carolina Sabrina E. Smith, MD, PhD Fellow Academy of Medical Educators Attending Physician Pediatric Neurology Kaiser Permanente Oakland Medical Center Oakland, California Lauren G. Solan, MD, MEd Assistant Professor Department of Pediatrics Division of Pediatric Hospital Medicine University of Rochester Golisano Children’s Hospital Rochester, New York Danielle Soranno, MD Assistant Professor Pediatrics, Bioengineering & Medicine Pediatric Nephrology/The Kidney Center University of Colorado/Anschutz Medical Campus Children’s Hospital Colorado Aurora, Colorado Angela M. Statile, MD, MEd Assistant Professor Department of Pediatrics University of Cincinnati College of Medicine Director, Hospital Medicine Burnet Campus Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio Andrew A. Stec, MD† Associate Professor Department of Urology and Pediatrics Director of Pediatric Urology Medical University of South Carolina Charleston, South Carolina Andrew P. Steenhoff, MBBCh, DCH

Assistant Professor Department of Pediatrics University of Pennsylvania Medical Director, Global Health Center Division of Infectious Diseases The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Julie W. Stern, MD Clinical Professor Pediatrics, Divisions of Hematology & Oncology Director, Outreach Services, Division of Oncology Children’s Hospital of Pennsylvania Philadelphia, Pennsylvania Christopher C. Stewart, MD Professor Department of Pediatrics University of California, San Francisco San Francisco, California C. Matthew Stewart, MD, PhD Assistant Professor Otolaryngology, Head and Neck Surgery The Johns Hopkins University School of Medicine Baltimore, Maryland F. Dylan Stewart, MD, FACS Assistant Professor of Surgery Johns Hopkins Children’s Center Director, Pediatric Trauma Center Director, Pediatric Burn Center Baltimore, Maryland Rosalyn W. Stewart, MD, MS, MBA Associate Professor Departments of Medicine and Pediatrics The Johns Hopkins University School of Medicine Medical Director, Care Coordination and Resource Management Johns Hopkins Hospital Baltimore, Maryland Constantine A. Stratakis, MD, D(med)Sci Scientific Director

Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) National Institutes of Health (NIH) Chief, Section on Genetics & Endocrinology (SEGEN), NICHD, NIH Bethesda, Maryland Paul K. Sue, MD, CM Assistant Professor Department of Pediatrics Division of Pediatric Infectious Disease University of Texas Southwestern Medical Center Children’s Medical Center of Dallas Dallas, Texas Kathleen E. Sullivan, MD, PhD† Professor Department of Pediatrics Perelman School of Medicine at University of Pennsylvania Chief, Division of Allergy and Immunology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania John I. Takayama, MD, MPH Professor of Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Jie Tang, MD, MS Pediatric Cardiology Fellow The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Sonny T. Tat, MD, MPH Assistant Clinical Professor of Pediatric Emergency Medicine Department of Emergency Medicine University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Anupama R. Tate, DMD, MPH Associate Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Director

Oral Health Advocacy & Research Children’s National Health Systems Washington, DC Danna Tauber, MD, MPH Assistant Professor Department of Pediatrics Eudowood Division of Pediatric Respiratory Sciences The Johns Hopkins University School of Medicine Baltimore, Maryland Jesse A. Taylor, MD, FACS Mary Downs Endowed Chair of Pediatric Craniofacial Fellowship Co-Director, CHOP Cleft Team Plastic, Reconstructive, and Craniofacial Surgery The University of Pennsylvania The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania David T. Teachey, MD Associate Professor of Pediatrics Department of Hematology/Oncology University of Pennsylvania, Perelman School of Medicine Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Peter Tebben, MD Pediatric Endocrinologist Departments of Internal Medicine and Pediatrics Division of Endocrinology Mayo Clinic College of Medicine and Science Rochester, Minnesota Jennifer A. F. Tender, MD, IBCLC Assistant Professor Department of Pediatrics The George Washington University School of Medicine & Health Sciences Staff Pediatrician Division of General Pediatrics The Children’s National Health System Washington, DC Amit Thakral, MD, MBA† Pediatric Rheumatology Fellow

Ann & Robert H. Lurie Children’s Hospital of Chicago Northwestern University Chicago, Illinois Sheila Thampi, MD Kaiser Permanente Santa Clara, California Liu Lin Thio, MD, PhD Associate Professor Department of Neurology, Pediatrics, and Neuroscience Washington University School of Medicine Director, Pediatric Epilepsy Center St. Louis Children’s Hospital St. Louis, Missouri Joanna E. Thomson, MD, MPH† Assistant Professor Department of Pediatrics University of Cincinnati College of Medicine Division of Hospital Medicine Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio John E. Tis, MD Associate Professor of Orthopedic Surgery Division of Pediatric Orthopedics Division of Sports Medicine Johns Hopkins School of Medicine Baltimore, Maryland James R. Treat, MD Associate Professor Clinical Pediatrics and Dermatology Perelman School of Medicine at the University of Pennsylvania Fellowship and Education Directors, Pediatric Dermatology The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Maria Trent, MD, MPH Professor of Pediatrics Adolescent/Young Adult Medicine The Johns Hopkins University School of Medicine Baltimore, Maryland

Rupal H. Trivedi, MD, MSCR Associate Professor Department of Ophthalmology Storm Eye Institute Medical University of South Carolina Charleston, South Carolina Patrika M. Tsai, MD, MPH† Associate Professor Department of Pediatrics Division of Pediatric Gastroenterology, Hepatology, and Nutrition University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Nicholas Tsarouhas, MD Professor of Clinical Pediatrics Perelman School of Medicine at the University of Pennsylvania Medical Director, CHOP Emergency Transport Team Attending Physician, Emergency Department The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Susma Vaidya, MD, MPH Assistant Professor of Pediatrics The George Washington University School of Medicine & Health Sciences Children’s National Medical Center Washington, DC Pamela L. Valentino, MD, MSc, FRCP(C) Assistant Professor Department of Pediatrics Section of Gastroenterology and Hepatology Yale University School of Medicine Yale-New Haven Children’s Hospital New Haven, Connecticut Kristin L. Van Buren, MD, MEd Assistant Professor of Pediatrics Department of Pediatrics Division of Pediatric Gastroenterology, Hepatology, and Nutrition Baylor College of Medicine Texas Children’s Hospital Houston, Texas

Stanley R. Vance Jr., MD Assistant Professor of Clinical Pediatrics University of California, San Francisco (UCSF) UCSF Department of Pediatrics and Division of Adolescent and Young Adult Medicine UCSF Child and Adolescent Gender Center San Francisco, California Hilary Vernon, MD, PhD† Assistant Professor Department of Pediatrics The Johns Hopkins University School of Medicine Director Medical Biochemical Genetics Fellowship McKusick-Nathans Institute of Genetic Medicine Baltimore, Maryland Elizabeth R. Volkmann, MD, MS Co-Director, UCLA Connective Tissue Disease-Related Interstitial Lung Disease (CTD-ILD) Program Department of Medicine Ronald Reagan UCLA Medical Center Los Angeles, California David M. Vu, MD Instructor Department of Pediatrics Division of Infectious Diseases Stanford University School of Medicine Stanford, California Patricia Vuguin, MD, MSc Associate Professor of Pediatrics Pediatric Endocrinology Columbia University College of Physicians and Surgeons Director, Pediatric Fellowship Program Division of Pediatric Endocrinology Morgan Stanley Children’s Hospital of New York-Presbyterian New York, New York R. Paul Wadwa, MD Associate Professor Department of Pediatrics University of Colorado School of Medicine Medical Director Pediatric Division

Barbara Davis Center for Childhood Diabetes Aurora, Colorado Lars M. Wagner, MD Professor of Pediatrics Chief, Division of Pediatric Hematology/Oncology University of Kentucky Kentucky Children’s Hospital Lexington, Kentucky Justin T. Wahlstrom, MD Assistant Professor Department of Pediatrics University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco, California Cynthia X. Wang, MD Autoimmune Neurology Fellow Department of Neurology and Neurotherapeutics University of Texas Southwestern Medical Center Children’s Medical Center of Dallas Dallas, Texas Marie E. Wang, MD, MPH† Clinical Instructor Division of Pediatric Hospital Medicine Stanford University School of Medicine Lucile Packard Children’s Hospital Stanford Palo Alto, California Ming-Hsien Wang, MD, FAAP† Associate Professor Department of Pediatric Urology Baylor College of Medicine Texas Children’s Hospital The Woodlands, Texas Ari Wassner, MD Assistant Professor Department of Pediatrics Harvard Medical School Director Thyroid Program

Boston Children’s Hospital Boston, Massachusetts Ami Waters, MD, MPH Assistant Professor of Internal Medicine-Pediatrics University of Texas Southwestern Medical Center Dallas, Texas Co-Medical Director, Last Mile Health Liberia Andrew J. Wehrman, MD Fellow Physician Division of Gastroenterology, Hepatology, and Nutrition The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Dascha C. Weir, MD Associate Director The Celiac Disease Program Boston Children’s Hospital Boston, Massachusetts Peter Weiser, MD Associate Professor Department of Pediatrics Division of Rheumatology University of Alabama at Birmingham Children’s of Alabama Birmingham, Alabama Dana A. Weiss, MD Assistant Professor Department of Surgery in Urology University of Pennsylvania Attending Physician The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Benjamin M. Whittam, MD, MS Assistant Professor of Urology Riley Hospital for Children at Indiana University Medical Center Indianapolis, Indiana Sharon O. Wietstock, MD, MSc† Child Neurology Resident

University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Rebekah Williams, MD, MS, FAAP Assistant Professor Department of Clinical Pediatrics Section of Adolescent Medicine Indiana University School of Medicine Indianapolis, Indiana M. Edward Wilson, MD Professor Department of Ophthalmology and Pediatrics Storm Eye Institute Department of Ophthalmology Medical University of South Carolina Charleston, South Carolina Erica Winnicki, MD Assistant Professor of Pediatrics Division of Pediatric Nephrology University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Elaine C. Wirrell, MD Director, Pediatric Epilepsy Consultant Professor, Child and Adolescent Neurology and Epilepsy Mayo Clinic Rochester, Minnesota Thomas E. Wiswell, MD Attending Neonatologist Kaiser Permanente Moanalua Medical Center Honolulu, Hawaii Char M. Witmer, MD, MSCE Clinical Associate Professor of Pediatrics Division of Hematology Perelman School of Medicine, University of Pennsylvania Assistant Director, Hemostasis and Thrombosis Center The Children’s Hospital of Philadelphia

Philadelphia, Pennsylvania Margaret S. Wolff, MD Assistant Professor Department of Emergency Medicine and Pediatrics Director, Center for Experiential Learning and Assessment University of Michigan C.S. Mott Children’s Hospital Ann Arbor, Michigan Mark L. Wolraich, MD Shaun Walters Professor of Pediatrics Chief, Section of Developmental and Behavioral Pediatrics University of Oklahoma Health Sciences Center (OUHSC) OU Child Study Center Oklahoma City, Oklahoma Lily C. Wong-Kisiel, MD Assistant Professor Department of Neurology Division of Child and Adolescent Neurology Division of Epilepsy Department of Neurology Mayo Clinic Rochester, Minnesota George A. (Tony) Woodward, MD, MBA Professor, Department of Pediatrics Norcliffe Foundation Endowed Chair Pediatric Emergency Medicine University of Washington School of Medicine Medical Director, Emergency and Transport Services Pediatric Medical Director, Airlift Northwest Seattle Children’s Hospital Seattle, Washington Bethany Woomer, MD Clinical Instructor and Fellow Division of Pediatric Hospital Medicine University of California, San Francisco UCSF Benioff Children’s Hospital San Francisco San Francisco, California Hsi-Yang Wu, MD Associate Professor Department of Urology

Stanford University Medical Center Director, Pediatric Urology Fellowship Program Lucile Packard Children’s Hospital Stanford Palo Alto, California Desale Yacob, MD Assistant Professor Department of Clinical Pediatrics The Ohio State University Medical Director Center for Motility and Functional GI disorders Division of Pediatric Gastroenterology, Hepatology, and Nutrition Nationwide Children’s Hospital Columbus, Ohio Jennifer H. Yang, MD† Associate Professor Department of Urology Division of Pediatric Urology University of California, Davis School of Medicine UC Davis Children’s Hospital Sacramento, California Michael Yaron, MD Professor Department of Emergency Medicine University of Colorado School of Medicine Denver, Colorado Yvette E. Yatchmink, MD, PhD Associate Professor Department of Pediatrics Clinician Educator Division of Developmental-Behavioral Pediatrics The Warren Alpert Medical School of Brown University Hasbro Children’s Hospital Providence, Rhode Island M. Elizabeth M. Younger, CRND, PhD Assistant Professor Department of Pediatrics The Johns Hopkins University School of Medicine Baltimore, Maryland

Nazlee Zebardast, MD, MSc Clinical Fellow Wilmer Eye Institute, The Johns Hopkins Hospital Baltimore, Maryland Ryan W. Zipper, MD† Resident Physician—Urology Medical University of South Carolina Charleston, South Carolina Naamah Levy Zitomersky, MD Instructor in Pediatrics Harvard Medical School Staff Physician, Gastroenterology Boston Children’s Hospital Boston, Massachusetts Monica Zlotnicki, MD Fellow Pediatric Hematology and Oncology UCSF Benioff Children’s Hospital Oakland Oakland, California † The views expressed are those of the authors and do not reflect the official policy of the Department of the Army, Department of the Navy, Department of the Air Force, the Department of Defense, or the United States Government.

SEVENTH EDITION AUTHOR ACKNOWLEDGMENTS The editors and authors of the eighth edition gratefully acknowledge the past contributions of the following previous edition authors: Fizan Abdullah Garrick A. Applebee Julia Belkowitz Anthony Chan Rohini Coorg Aarti Dalal Peter de Blank Marissa Janel DeFreitas Sophia D. Delpe Jennifer DiPace Mark F. Ditmar Stacy E. Dodt Saskia Gex Rose C. Graham Daphne M. Hasbani Mayada A. Helal Brian M. Inouye John L. Jefferies Erin E. Karski Greggy D. Laroche Ilse A. Larson Paul R. Lee Rebecca K. Lehman Tobias Loddenkemper Richard Loffhagen Kimberly M. Lumpkins Bradley S. Marino Renée Marquardt Heather L. Meluskey Shina Menon Caitlin Messner Avindra Nath Jason G. Newland Peter D. Ngo Heather Olson Hee-Jung Park

Christopher J. Petit Laura Robertson Julia Shaklee Sammons Gordon E. Schutze Pirouz Shamszad David D. Sherry Stephan Siebel John Stirling Waqar Waheed

CONTENTS Preface Contributing Authors Seventh Edition Author Acknowledgments Abdominal Mass Abdominal Migraine Abdominal Pain Abnormal Bleeding Acetaminophen (Paracetamol) Poisoning Acne Acute Drug Withdrawal Acute Kidney Injury Acute Liver Failure Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Adenovirus Infection Alcohol (Ethanol) Intoxication Allergic Child Alopecia (Hair Loss) Alpha-1 Antitrypsin Deficiency Altitude Illness Ambiguous Genitalia (Disorders of Sexual Development) Amblyopia Amebiasis Amenorrhea Anaerobic Infections Anaphylaxis Anemia of Chronic Disease (Anemia of Inflammation) Ankyloglossia Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA) Anorexia Nervosa Anthrax Aplastic Anemia Appendicitis Arthritis, Juvenile Idiopathic (Rheumatoid) Ascaris lumbricoides (Ascariasis) Ascites Aspergillosis Asplenia/Hyposplenia

Asthma Ataxia Atelectasis Atopic Dermatitis Atrial Septal Defect Attention-Deficit/Hyperactivity Disorder Autism Spectrum Disorder Autoimmune Hemolytic Anemia Avascular (Aseptic) Necrosis of the Femoral Head (Hip) Babesiosis Back Pain Barotitis Bell Palsy Bezoars Biliary Atresia Bladder and Bowel Dysfunction Blastomycosis Blepharitis Bone Marrow and Stem Cell Transplant Botulism and Infant Botulism Brachial Plexus Palsy (Perinatal) Brain Abscess Brain Injury, Traumatic Brain Tumor Branchial Cleft Malformations Breast Abscess Breastfeeding Breath-Holding Spells Brief Resolved Unexplained Event (Apparent Life-Threatening Event) Bronchiolitis (See Also: Respiratory Syncytial Virus) Bronchopulmonary Dysplasia (BPD) Bruising Bruxism Bulimia Campylobacter Infections Cancer Therapy Late Effects Candidiasis Carbon Monoxide Poisoning Cardiomyopathy Cataract Cat-Scratch Disease

Cavernous Sinus Syndrome Cavernous Transformation and Portal Vein Obstruction Celiac Disease Cellulitis Cerebral Palsy Cervicitis Chancroid Chest Pain Chickenpox (Varicella, Herpes Zoster) Chikungunya Virus Child Abuse, Physical Chlamydia Trachomatis Infection Chlamydophila (Formerly Chlamydia) pneumoniae Infection Cholelithiasis (Gallstones) Cholera Chronic Diarrhea Chronic Granulomatous Disease Chronic Hepatitis Chronic Kidney Disease Cirrhosis Cleft Lip and Palate Clubfoot Coarctation of Aorta Coccidioidomycosis Colic Coma Common Variable Immunodeficiency Complement Deficiency Concussion Congenital Adrenal Hyperplasia Congenital Hepatic Fibrosis Congestive Heart Failure Conjunctivitis Constipation Contact Dermatitis Contraception Cor Pulmonale Costochondritis Cough Crohn Disease Croup (Laryngotracheobronchitis)

Crying Cryptococcal Infections Cryptorchidism Cryptosporidiosis Cushing Syndrome Cutaneous Larva Migrans Cyclic Vomiting Syndrome Cyclospora Cystic Fibrosis Cytomegalovirus Infections Daytime Incontinence Dehydration 22q11.2 Deletion Syndrome (DiGeorge Syndrome, Velocardiofacial Syndrome) Dengue Virus Dental Caries Dental Health and Prevention Dental Infections Dental Trauma Depression Dermatomyositis/Polymyositis Developmental Delay Developmental Dysplasia of the Hip Diabetes Insipidus Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetic Ketoacidosis Diaper Rash Diaphragmatic Hernia (Congenital) Diarrhea Diphtheria Diskitis Disseminated Intravascular Coagulation Down Syndrome (Trisomy 21) Drowning Dysfunctional Uterine Bleeding Dysmenorrhea Dyspnea Dysuria Earache Ebola Virus Disease Edema

Ehrlichiosis and Anaplasmosis Encephalitis Encopresis Endocarditis Enuresis Eosinophilic Esophagitis Epididymitis Epiglottitis Epstein-Barr Virus (Infectious Mononucleosis) Erythema Multiforme Erythema Nodosum Ewing Sarcoma Excoriation Disorder Exstrophy–Epispadias Complex Failure to Thrive (Weight Faltering) Feeding Disorders Fetal Alcohol Syndrome Fever and Petechiae Fever of Unknown Origin Floppy Infant Syndrome Follow-Up of NICU Graduates Food Allergy Food Hypersensitivity (Non–IgE-Mediated, Gastrointestinal) Food Poisoning or Foodborne Illness Fragile X Syndrome Frostbite Functional Diarrhea of Infancy (Toddler’s Diarrhea) Fungal Skin Infections (Dermatophyte Infections, Candidiasis, and Tinea Versicolor) Gastritis Gastroesophageal Reflux Germ Cell Tumors German Measles (Third Disease, Rubella) Giardiasis Gingivitis Glaucoma–Congenital Glomerulonephritis Glucose-6-Phosphate Dehydrogenase Deficiency Goiter Gonococcal Infections Graft-Versus-Host Disease Graves Disease

Growth Hormone Deficiency Guillain-Barré Syndrome Gynecomastia Hand, Foot, and Mouth Disease Head Banging Headache and Migraine Heat Stroke and Related Illness Hemangiomas and Other Vascular Lesions Hematuria Hemolysis Hemolytic Disease of the Fetus and Newborn Hemolytic Uremic Syndrome Hemophilia Hemoptysis Henoch-Schönlein Purpura Hepatomegaly Hereditary Angioedema (C1 Esterase Deficiency) Hereditary Spherocytosis Herpes Simplex Virus Hiccups (Singultus) Hirschsprung Disease Histiocytosis Histoplasmosis Hodgkin Lymphoma Human Immunodeficiency Virus Infection Human Papillomavirus Hydrocele Hydrocephalus Hydronephrosis Hypercalcemia Hyperimmunoglobulinemia E Syndrome Hyperleukocytosis Hyperlipidemia Hypertension Hypocalcemia Hypogammaglobulinemia Hypoglycemia Hypokalemia Hyponatremia Hypophosphatemic Disorders Hypopituitarism

Hypoplastic Left Heart Syndrome Hypospadias Hypothyroidism, Acquired Hypothyroidism, Congenital Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) Immune Deficiency Immune Thrombocytopenic Purpura Immunoglobulin A Deficiency Immunoglobulin A Nephropathy Imperforate Anus Impetigo Infantile Spasms Influenza Inguinal Hernia Intellectual Disability Intestinal Obstruction Intoeing–Tibial/Femoral Torsion Intracranial Hemorrhage Intussusception Iron Deficiency Anemia Iron Poisoning Irritable Bowel Syndrome Jaundice Jaundice Associated with Breastfeeding Kawasaki Disease Knee Pain, Anterior/Patellofemoral Malalignment Syndrome Lacrimal Duct Obstruction Lactose Intolerance Lead Poisoning Learning Disabilities Leukocytosis Lice (Pediculosis) Long QT Syndrome Lower GI Bleeding Lupus Erythematosus Lyme Disease Lymphadenopathy Lymphedema Lymphoproliferative Disorders Malabsorption Malaria

Malnutrition Mammalian Bites Mastoiditis Measles (Rubeola) Meckel Diverticulum Meconium Aspiration Syndrome Mediastinal Mass Megaloblastic Anemia Meningitis Meningococcemia Mesenteric Adenitis Metabolic Diseases in Acidotic Newborns Metabolic Diseases in Hyperammonemic Newborns Metabolic Diseases in Hypoglycemic Newborns Metabolic Syndrome Methemoglobinemia Microcytic Anemia Milia Morphea (Localized Scleroderma) Multicystic Dysplastic Kidney Mumps/Parotitis Munchausen Syndrome by Proxy (Medical Child Abuse) Muscular Dystrophies Myasthenia Gravis Myocarditis Narcolepsy Neck Masses Necrotizing Enterocolitis Neonatal Abstinence Syndrome Neonatal Alloimmune Thrombocytopenia Neonatal Apnea Neonatal Cholestasis Neonatal Encephalopathy Nephrotic Syndrome Neural Tube Defects Neuroblastoma Neurofibromatosis-1 Neutropenia Non-Hodgkin Lymphoma Nontuberculous Mycobacterial Infections (Atypical Mycobacterial Infections) Nosebleeds (Epistaxis)

Obesity Obsessive-Compulsive Disorder Omphalitis Opioid Intoxication Osteogenesis Imperfecta Osteomyelitis Osteosarcoma Otitis Externa Otitis Media Pallor Pancreatic Pseudocyst Pancreatitis Parvovirus B19 (Erythema Infectiosum, Fifth Disease) Patent Ductus Arteriosus Pelvic Inflammatory Disease Penile and Foreskin Problems Pericarditis Periodic Breathing Periorbital Cellulitis Perirectal Abscess Peritonitis Peritonsillar Abscess Persistent Pulmonary Hypertension of the Newborn Perthes Disease Pertussis Pharyngitis Phimosis and Paraphimosis Photosensitivity Pinworms Plague Pleural Effusion Pneumocystis jiroveci (Previously Known as Pneumocystis carinii Pneumonia) Pneumonia—Bacterial Pneumothorax Polyarteritis Nodosa Polycystic Kidney Disease Polycystic Ovary Syndrome Polycythemia Polyps, Intestinal Portal Hypertension Posterior Urethral Valves

Precocious Puberty Premature Adrenarche Premature Thelarche Premenstrual Syndrome Primary Adrenal Insufficiency Prion Diseases (Transmissible Spongiform Encephalopathies) Proteinuria Pruritus Psittacosis Psoriasis Pubertal Delay Pulmonary Embolism Pulmonary Hypertension Purpura Fulminans Pyelonephritis Pyloric Stenosis Rabies Radial Head Subluxation (Nursemaid’s Elbow) Rectal Prolapse Refractive Error Renal Artery Stenosis Renal Tubular Acidosis Renal Venous Thrombosis Respiratory Distress Syndrome Respiratory Syncytial Virus (See Also: Bronchiolitis) Retinoblastoma Retinopathy of Prematurity Retropharyngeal Abscess Reye Syndrome Rhabdomyolysis Rhabdomyosarcoma Rheumatic Fever Rhinitis, Allergic Rickets/Osteomalacia Rickettsial Disease Rocky Mountain Spotted Fever Roseola Rotavirus Salicylate (Aspirin) Poisoning Salmonella Infections Sarcoidosis

Scabies Scarlet Fever Scoliosis Seborrheic Dermatitis Seizures, Partial and Generalized Seizures–Febrile Separation Anxiety Disorder Sepsis Sepsis, Neonatal Septic Arthritis Serum Sickness Severe Acute Respiratory Syndrome (SARS) Severe Combined Immunodeficiency Sexual Abuse Short Stature Short-Bowel Syndrome Sickle Cell Disease Sinusitis Sleep Apnea—Obstructive Sleep Apnea Syndrome Slipped Capital Femoral Epiphysis Smallpox (Variola Virus) Snake and Insect Bites Social Anxiety Disorder Sore Throat Speech Delay Speech Problems Spinal Muscular Atrophy Splenomegaly Spondyloarthropathy Staphylococcal Scalded Skin Syndrome Status Epilepticus Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Stomatitis Strabismus Strep Infection: Invasive Group A β-Hemolytic Streptococcus Stroke Stuttering Subdural Hematoma Substance Use Disorders Sudden Infant Death Syndrome (SIDS) Suicide

Superior Mesenteric Artery Syndrome Supraventricular Tachycardia Sympathomimetic Poisoning Syncope Syndrome of Inappropriate Antidiuretic Hormone Secretion Synovitis–Transient Syphilis Systemic Sclerosis (Systemic Scleroderma) Tapeworm Teething Tendonitis and Tendinosis Testicular Torsion Tetanus Tetralogy of Fallot Thalassemia Thoracic Insufficiency Syndrome Thrombosis Tick Fever Tics Toxic Alcohols Toxic Shock Syndrome Toxoplasmosis Tracheitis Tracheoesophageal Fistula and Esophageal Atresia Tracheomalacia/Laryngomalacia Transfusion Reaction Transgender Youth Transient Erythroblastopenia of Childhood Transient Tachypnea of the Newborn Transposition of the Great Arteries Transverse Myelitis Trichinosis Trichotillomania Tuberculosis Tuberous Sclerosis Complex Tularemia Turner Syndrome Ulcerative Colitis Upper Gastrointestinal Bleeding Ureteropelvic Junction Obstruction Urinary Tract Infection

Urolithiasis Urticaria (Hives) Vaccine Adverse Events Vaccine Refusal Vaginitis Varicocele Vascular Brain Lesions (Congenital) Ventricular Septal Defect Ventricular Tachycardia Vesicoureteral Reflux Viral Hepatitis Volvulus Vomiting von Willebrand Disease Warts Weight Loss West Nile Virus (and Other Arbovirus Encephalitis) Wheezing Wilms Tumor Wilson Disease Wiskott-Aldrich Syndrome Yersinia enterocolitica Zika Virus Infections in Children Appendix I: The 5-Minute Educator Appendix I Part 1: Precepting Appendix I Part 2: Direct Observation Appendix I Part 3: Feedback Appendix I Part 4: Clinical Reasoning Appendix II: Cardiology Laboratory Appendix III: Syndromes Glossary Appendix IV: Tables and Figures Index

ABDOMINAL MASS Maireade E. McSweeney, MD, MPH

BASICS DESCRIPTION A palpable lesion or fullness in the abdominal cavity which may or may not be related to abdominal viscera or a lesion detected on abdominal imaging; the mass may be abdominal or retroperitoneal in origin. EPIDEMIOLOGY Etiologies for abdominal masses are varied, and the differential depends on age and anatomic location. Majority are nonsurgical in nature; may be associated with constipation Approximately 57% of abdominal masses in children are due to organomegaly (hepatomegaly or splenomegaly). Most abdominal masses in infants originate from the kidney and are benign (e.g., hydronephrosis); Wilms tumor is the most common malignant tumor of the kidney seen in childhood. Liver masses account for 5–6% of all pediatric intra-abdominal masses; hepatoblastoma is the most common primary liver tumor in children, often presenting at 1 to 3 years of age. RISK FACTORS Certain genetic disorders/syndromes are associated with increased risk of tumor development. Patients with Beckwith-Wiedemann syndrome; Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR); and Denys-Drash syndrome are at increased risk of Wilms tumor and require regular screening. GENERAL PREVENTION Dependent on whether or not the mass or lesion is related to a modifiable factor (e.g., a retained foreign body requires parental or patient counseling for prevention) PATHOPHYSIOLOGY Varies based on the type of mass seen ETIOLOGY Stomach – Gastric distension or gastroparesis – Duplication – Foreign body or bezoar – Gastric torsion – Gastric tumor (lymphoma, sarcoma) Intestine – Feces (constipation) – Intestinal distension or toxic megacolon

– Foreign body – Meconium ileus – Duplication – Volvulus – Intussusception – Intestinal atresia or stenosis – Malrotation – Complications of inflammatory bowel disease (abscess, phlegmon) – Appendiceal inflammation – Meckel diverticulum or abscess – Duodenal hematoma (trauma) – Lymphoma, adenocarcinoma, GI stromal tumor – Carcinoid (appendiceal) Liver – Hepatomegaly due to intrinsic liver disease Hepatitis (e.g., infectious, autoimmune) Metabolic or storage disorders (e.g., Wilson disease, glycogen storage disease) Infiltration of liver (cyst, tumors) Biliary obstruction Vascular obstruction/impaired venous congestion (Budd-Chiari syndrome, congestive heart failure) – Cystic disease (e.g., Caroli disease) – Solid tumor (hepatoblastoma; hepatocellular carcinoma; hepatic adenoma; or other diffuse, systemic, neoplastic process) – Vascular tumor (hemangioma or hemangioendothelioma) – Other: hamartomas, focal nodular hyperplasia Gallbladder/biliary tract – Choledochal cyst – Hydrops of gallbladder – Obstruction (stone, stricture, trauma) Spleen – Congenital cysts – Storage disease (e.g., Gaucher, Niemann-Pick) – Langerhans cell histiocytosis – Leukemia – Hematologic (hemolytic disease [e.g., sickle cell] or other RBC disorders [e.g., hereditary spherocytosis]) – Portal hypertension – Wandering spleen Pancreas – Congenital cysts – Pseudocyst (trauma, pancreatitis)

– Pancreatoblastoma – Neuroendocrine tumors (insulinomas, gastrinomas) – Solid and papillary epithelial neoplasms Kidney – Hydronephrosis or ureteropelvic obstruction – Multicystic dysplastic kidney – Polycystic disease – Tumor (mesoblastic nephroma, Wilms tumor, renal cell carcinoma) – Renal vein thrombosis – Cystic nephroma Bladder – Bladder distension – Neurogenic bladder Adrenal – Adrenal hemorrhage – Adrenal abscess – Neuroblastoma – Pheochromocytoma Uterus – Pregnancy – Hematocolpos – Hydrocolpos or hydrometrocolpos Ovary – Cysts (dermoid, follicular) – Torsion – Germ cell tumor Peritoneal – Ascites – Teratoma Abdominal wall – Umbilical/inguinal/ventral hernia – Omphalocele/gastroschisis – Urachal cyst – Trauma (rectus hematoma) – Tumor (fibroma, lipoma, rhabdomyosarcoma) Omentum/mesentery – Cysts – Mesenteric fibromatosis – Mesenteric adenitis Other – Tumors (liposarcoma, leiomyosarcoma, fibrosarcoma, mesothelioma)

– Intra-abdominal testicle (torsion) – Lymphangioma – Fetus in fetu – Sacrococcygeal teratoma

DIAGNOSIS Approach to patient – When evaluating a pediatric abdominal mass, an organized approach is critical: Phase 1: Perform a careful clinical history and abdominal examination in order to help assess clinical symptoms and duration of symptoms and approximate anatomic location of the mass. Phase 2: Perform diagnostic tests: ■ Obtain abdominal x-ray to assess for bowel obstruction, fecal load, or mass effect; obtain ultrasound to identify organ of origin and tissue components (e.g., cystic, hemorrhage). ■ Laboratory testing as indicated – Tips for screening problems Constipation and fecal impaction can present as a large, hard mass extending from the pubis. In neonates, a palpable liver edge can be normal; assess the total liver span. In infants, a full bladder is often mistaken for an abdominal mass. Gastric distention should be considered in all children who present with a tympanitic epigastric mass. Splenomegaly may be associated with a systemic oncologic or infectious process (e.g., lymphoma or Epstein-Barr virus). HISTORY Patients may be asymptomatic or may have some of the symptoms outlined below. Question: Weight loss? Significance: malignancy, inflammatory bowel disease Question: Fever? Significance: infection, malignancy Question: Jaundice? Significance: hepatobiliary or hematologic disease Question: Hematuria or dysuria? Significance: renal disease Question: Vomiting, bilious vomiting, or early satiety? Significance: intestinal obstruction Question: Abdominal pain? Significance: constipation, appendicitis, intussusception, intestinal obstruction Question: Frequency and quality of bowel movements? Significance: constipation, intussusception, compression of bowel by mass Question: Bleeding or bruising? Significance: liver disease, coagulopathy Question: Pallor or weakness?

Significance: sign of anemia or blood loss Question: History of abdominal trauma? Significance: pancreatic pseudocyst, duodenal hematoma Question: Sexual activity? Significance: pregnancy Question: Age of patient? Significance: – In neonates, the most common origin of abdominal masses are genitourinary (cystic kidney disease, hydronephrosis). – In adolescent-aged girls, ovarian disorders, hematocolpos, and pregnancy should be considered. – Most common malignant abdominal tumors by age: (i) infants: neuroblastoma, Wilms tumor; (ii) children: Wilms tumor, sarcomas, germ cell tumors; (iii) children >10 years of age: sarcomas, germ cell tumors, and abdominal lymphomas PHYSICAL EXAM Finding: General appearance? Significance: ill appearance or cachexia point toward infection or malignancy Finding: Location of abdominal mass? Significance: – Left lower quadrant: feces, ovarian process, ectopic pregnancy – Left upper quadrant: splenomegaly, anomaly of the kidney – Right lower quadrant: abscess (inflammatory bowel disease), intestinal phlegmon, appendicitis, intussusception, ovarian process, ectopic pregnancy – Right upper quadrant: liver, gallbladder, biliary tree, or intestine – Epigastric: abnormality of the stomach (bezoar, torsion), pancreas (pseudocyst), or enlarged liver – Suprapubic: pregnancy, hydrometrocolpos, hematocolpos, posterior urethral valves – Flank: renal disease (cystic kidney, hydronephrosis, Wilms tumor) Finding: Characteristics of abdominal mass? Significance: Mobility, tenderness, firmness, smoothness, and/or irregularity of the surface of the mass can provide clues to its significance. Finding: Hard and immobile mass? Significance: tumor Finding: Extension of mass across midline or into pelvis? Significance: tumor, hepatomegaly, splenomegaly Finding: Percussion of mass? Significance: Dullness indicates a solid mass; tympany indicates a hollow organ. Finding: Shifting dullness, fluid wave? Significance: ascites Finding: Skin exam? Significance: Bruising and petechiae may occur with coagulopathy related to liver disease and malignant infiltration of bone marrow; café au lait spots are associated with neurofibromas. Finding: Lymphadenopathy or lymphadenitis?

Significance: systemic process either malignant or infectious Finding: Peritoneal signs? Significance: appendicitis, bowel obstruction, or perforation; indication for urgent surgical consultation Finding: Rectal bleeding? Significance: intestinal inflammation, polyp, or other bleeding lesion DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Test: CBC with differential Significance: anemia, hemolysis Test: chemistry panel Significance: – Renal disease: BUN and creatinine levels – Liver disease (bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, PT/PTT) – Gallbladder disease (bilirubin, GGT) – Pancreatic disease: amylase/lipase levels – Intestinal disease: hypoalbuminemia Test: uric acid and lactate dehydrogenase levels Significance: elevated in the setting of rapid cell turnover of solid tumors Test: serum quantitative β-human chorionic gonadotropin (hCG) Significance: pregnancy, germ cell tumor Test: elevated α-fetoprotein (AFP) level Significance: hepatoblastoma Test: urinalysis Significance: Blood or protein in the urine may suggest a renal etiology. Plain radiographs – Evaluate for intestinal obstruction (dilated bowel loops, air-fluid levels), bowel gas pattern, calcifications, or fecal impaction; urinary retention Ultrasound – Can identify the origin of the mass and differentiate between solid and cystic tissue; Doppler ability can help assess vascularity. Disadvantage is operator variability, and visualization may be limited by overlying bowel gas. – May allow for ultrasound guided biopsies of mass lesions CT scan – Can provide more detail when there is overlying gas or bone; if malignancy is suspected, should also do chest in addition to abdomen and pelvis MRI – Vascular lesions of liver, major vessels, and tumors Nuclear medicine – Radioisotope cholescintigraphy (HIDA) scan of liver, gallbladder/biliary tree – Meckel scan: can identify gastric mucosa contained within a Meckel diverticulum or intestinal duplication

– Intravenous urography to assess renal system Fluoroscopy – Upper GI studies and barium enema studies: may be of benefit when the mass involves the intestine – Voiding cystourethrogram (VCUG) to assess renal system

TREATMENT GENERAL MEASURES Immediate hospitalization for patients who present with an abdominal mass and/or signs of dehydration, intestinal obstruction, bleeding, feeding intolerance, or clinical decompensation In addition to initial diagnostic and laboratory testing, a pediatric surgical or oncologic consultation should be obtained as indicated. The remaining causes of abdominal masses require urgent care and timely evaluation and referral to appropriate specialists depending on location of the lesion. ISSUES FOR REFERRAL Except for the diagnosis of constipation, the presence of an abdominal mass in children requires immediate attention, and diagnostic studies should be performed expeditiously at a pediatric health care facility or by pediatric specialists trained in assessment and treatment of these various disorders. ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS Immediate hospitalization for patients who present with an abdominal mass and signs and/or symptoms of intestinal obstruction, distension, or peritoneal symptoms (intussusception, volvulus, gastric torsion, bezoar, foreign body, appendicitis) – Toxic megacolon – Ovarian torsion – Ectopic pregnancy – Biliary obstruction (stone, hydrops) – Fever – Anemia, coagulopathy – Pancreatitis (pseudocyst) The remaining causes of abdominal masses require urgent care and timely evaluation and referral to appropriate specialists.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Will be dictated by type of mass or lesion found

ADDITIONAL READING Chandler JC, Gauderer MW. The neonate with an abdominal mass. Pediatr Clin North Am. 2004;51(4):979–997.

Golden CB, Feusner JH. Malignant abdominal masses in children: quick guide to evaluation and diagnosis. Pediatr Clin North Am. 2002;49(6):1369–1392. Ladino-Torres MF, Strouse PJ. Gastrointestinal tumors in children. Radiol Clin North Am. 2011;49(4):665–677. Potisek NM, Antoon JW. Abdominal masses. Pediatr Rev. 2017;38(2):101–103. Stevenson RJ. Abdominal masses. Surg Clin North Am. 1985;65(6):1481–1504.

CODES ICD10 R19.00 Intra-abd and pelvic swelling, mass and lump, unsp site R16.0 Hepatomegaly, not elsewhere classified R16.1 Splenomegaly, not elsewhere classified

FAQ Q: What congenital anomaly can often serve as a lead point for volvulus or intussusception? A: Gastrointestinal duplication cysts Q: What type of therapy may result in quick resolution of a benign left lower quadrant fecal mass? A: Stool softener or other osmotic laxatives Q: What is the most common renal malignancy of childhood? A: Wilms tumor

ABDOMINAL MIGRAINE Desale Yacob, MD

BASICS DESCRIPTION Paroxysmal disorder of an acute onset, severe, noncolicky, periumbilical, or diffuse abdominal pain accompanied variably with nausea, vomiting, anorexia, headache, and pallor EPIDEMIOLOGY Incidence Occurs mostly in children; mean onset at age 7 years (3 to 10 years) Peak symptoms 10 to 12 years of age More common in girls (3:2) Prevalence May affect as many as 1–4% of children at some point in their lives Declining frequency toward adulthood RISK FACTORS Genetics Parents of affected children often have history of migraine headaches and motion sickness. ETIOLOGY May involve neuronal activity originating in the hypothalamus with involvement of the cortex and autonomic nervous system Serotonin is implicated and blockade of serotonin receptors may prevent abdominal migraine. Recent studies suggest involvement of local intestinal vasomotor factors. Abdominal migraine shares pathophysiologic mechanisms and clinical characteristics with cyclic vomiting syndrome and migraine headaches.

DIAGNOSIS Rome IV criteria—two episodes fulfilled for at least 6 months meeting all of the following criteria: Paroxysmal intense acute periumbilical, midline or diffuse abdominal pain episodes lasting an hour or more Episodes are separated by weeks to months. Pain that is incapacitating and interferes with normal activity Patterns and symptoms are stereotypical in the individual patient. Pain associated with ≥2 of the following: anorexia, nausea, vomiting, headache, photophobia, or pallor Symptoms cannot be explained by another medical condition based on appropriate evaluation.

HISTORY Migraine in the history of patient Ask about a family history of migraine headache or unexplained bouts of parental abdominal pain as children. Pain typically lasts 2 months, can either be of organic origin (anatomic, infectious, inflammatory, or metabolic) or, more frequently, part of a functional gastrointestinal disorder (FGID) based on specific diagnostic criteria (Rome IV). EPIDEMIOLOGY Abdominal pain is one of the most common complaints in pediatric patients. Chronic abdominal pain represents 2–4% of general pediatrics office visits and >50% of pediatric gastroenterology visits and can be associated with significant morbidity. Thus, chronic pain also warrants careful consideration and management. PATHOPHYSIOLOGY The nature of abdominal pain is multifactorial and may evolve in nature over time (i.e., in acute appendicitis, pain typically migrates from periumbilical to right lower quadrant). Visceral pain (particularly from small intestine) is often poorly localized and is described as dull, diffuse, cramping, or burning. Visceral pain may be associated with autonomic reflex responses (diaphoresis, pallor, nausea, and/or vomiting). More localized, sharp somatoparietal pain typically indicates peritoneal involvement (appendicitis, cholecystitis). Referred pain is related to the level of spinal cord entry of visceral afferent nerves (e.g., scapular pain in cholecystitis). ETIOLOGY Right upper quadrant – Cholelithiasis/cholecystitis – Hepatitis/perihepatitis – Nephrolithiasis – Ureteropelvic junction obstruction – Right lower lobe pneumonia Epigastric area – Gastroesophageal reflux disease (GERD) – Esophagitis (GERD, eosinophilic)

– Gastritis (NSAID, allergic, Helicobacter pylori, Crohn disease) – Functional dyspepsia – Ulcer disease (NSAID, H. pylori) – Pancreatitis – Cholecystitis – Gastric/small intestinal volvulus Left upper quadrant – Splenic hematoma – Renal disease (see above) – Left lower lobe pneumonia – Constipation Right lower quadrant – Appendicitis/perforation/psoas abscess – Mesenteric adenitis – Intussusception – Inflammatory bowel disease (IBD) – Infection (tuberculosis, Yersinia) – Ovarian/testicular torsion – Ectopic pregnancy – Inguinal hernia Left lower quadrant – Constipation – Colitis (inflammatory/infectious) – Sigmoid volvulus – Genitourinary disease Hypogastric area – Constipation – Colitis – Cystitis – Dysmenorrhea/uterine disease – Pelvic inflammatory disease Periumbilical area – FGID – Constipation – Gastroenteritis (infectious/eosinophilic) – Pancreatitis – Gastric/small bowel volvulus – Appendicitis (early) – Incarcerated umbilical hernia Diffuse – Constipation

– FGID – Giardiasis – Carbohydrate malabsorption – Celiac disease – Streptococcal/viral pharyngitis – IBD – Allergic/eosinophilic gastroenteritis – Ischemic necrotizing enterocolitis (NEC) – Perforation/peritonitis – Malrotation with volvulus – Lead/iron poisoning/pica syndrome – Cyclic vomiting syndrome – Porphyria – Sickle cell crisis – Familial Mediterranean fever – Diabetic ketoacidosis – Henoch-Schönlein purpura (HSP) – Tumor – Trauma – Hemolytic uremic syndrome (HUS)

DIAGNOSIS Initial step is to establish the acuity and severity of symptoms and to rule out a potentially life-threatening emergency (e.g., appendicitis, perforation, bowel obstruction associated with volvulus, adhesions, or intussusception). HISTORY Onset and duration of symptoms – Acute versus chronic Age of patient may be indicative of certain etiologies particularly in acute presentation. – NEC (newborn/prematurity), malrotation/volvulus (80% present in first month of life), intussusception (more frequent in infants/toddlers), foreign body ingestion in young child Localization and radiation of pain – May point to specific organ—see etiologies Triggering or relieving factors – Meals/spices, specific foods (lactose, sucrose) – General position with knees bent can be relieving in acute appendicitis. – Pain relieved by defecation (constipation) versus pain worsened by defecation (colitis) Bowel pattern and stool appearance – Stool frequency and consistency: diarrhea versus constipation

– Urgency or nocturnal diarrhea (colitis) – Presence of bloating and excessive flatulence (giardiasis, carbohydrate malabsorption) – Presence of mucus (may be normal but can be associated with colitis) – Hematochezia (fissure, hemorrhoid, polyp, colitis, HSP); if bright red “currant jelly” appearance, suspect intussusception – Melena (upper gastrointestinal bleeding/ulcer) – Pale/acholic stools (hepatic or biliary disease) – Perirectal disease (IBD) Anorexia/nausea/vomiting – If postprandial, indicative of upper gastrointestinal condition; nausea may be functional. – May indicate extraintestinal disease (urinary tract infection, UPJ obstruction, or pneumonia) – Hematemesis suggests esophagitis/gastritis; more significant blood volume suggests ulcer disease, Mallory-Weiss tear (lower esophagus). – Bilious emesis indicates intestinal obstruction (volvulus, intussusception, NEC in newborns). Dysphagia/food impaction – In older children, suspect eosinophilic esophagitis – GERD Fever – Acute infection, acute appendicitis, chronic inflammatory process Weight loss/growth failure/delayed puberty – Chronic inflammatory process, celiac disease Extraintestinal symptoms – Dysuria – Skin rash (atopy may point to eosinophilic process; purpura: abdominal pain may be first symptom of HSP) – Respiratory symptoms (pneumonia) – Arthralgias (IBD, HSP) Preexisting conditions (infectious diarrhea preceding HUS; hemoglobinopathy or cystic fibrosis risk factors for cholecystitis) Exposures – Lead/iron in young children – Travel/well water/pets (giardiasis) – Insect bite (HSP) – NSAID use (gastritis) – Tetracycline (pill esophagitis) Dietary history to assess fiber and fluid intake; excessive use of sugar-free gum (sorbitol malabsorption); intake of sucrose-, fructose-, or lactose-containing foods (disaccharidase deficiencies, most commonly lactose intolerance) Prior abdominal surgical history (adhesions) Family history of IBD, H. pylori, celiac disease, atopy, migraine Social history and identification of stressors, school attendance, signs of mood disorder

PHYSICAL EXAM In an acute setting, an abdominal exam may need to be serially performed, as location of pain may change over time. Signs of acute appendicitis: – Exquisite pain at McBurney point on percussion or palpation – Involuntary guarding – Rovsing sign (palpation LLQ), psoas sign, obturator sign – Rebound tenderness (peritoneal inflammation) – Pain on movement (walking, jumping) – Pain may be relieved temporarily if the appendix ruptures followed by signs of peritonitis. – Right upper quadrant pain on inspiration (cholecystitis) – Flank tenderness (renal pathology) – Perianal examination may reveal skin tags/fissures (constipation, IBD), perianal abscess (IBD), hemorrhoids. Rectal examination done carefully can be indicative of – Peritoneal irritation (appendicitis/peritonitis) – Hematochezia (IBD, HSP), perianal disease – Fecal retention/abnormal sphincter tone (anal stricture, absent relaxation of IAS suggesting anal achalasia) Skin rashes (eczema, purpura) Other signs of chronic disease include pallor, clubbing, edema. DIAGNOSTIC TESTS & INTERPRETATION Laboratory testing, if any, should be carefully guided by the history and clinical picture. – If a benign acute condition such as acute viral gastroenteritis is suspected, any further testing can be delayed with close follow-up (in absence of clinical evidence of dehydration). – In the presence of “red flags” (see “Issues for Referral”), blood and stool testing should be performed. CBC/differential – Leukocytosis (appendicitis/abscess, acute infectious process); normal white blood cell count may indicate low risk for acute appendicitis. – Anemia (gastrointestinal blood loss) – Microcytosis (chronic inflammation, IBD, celiac disease) Elevated ESR or CRP (acute infection, chronic inflammation) Hypoalbuminemia and low ferritin (IBD, celiac disease); diarrhea may be absent. Pancreatic enzymes, hepatic enzymes Fecal cultures in the presence of bloody diarrhea (colitis); ova and parasites (giardiasis) Fecal calprotectin and lactoferrin (inflammation or infection) Urinalysis to rule out urinary tract infection (leukocyturia may be present in acute appendicitis) Celiac screening (anti-tissue transglutaminase IgA or anti-endomysial IgA in presence of normal total IgA levels) should be considered if abdominal pain and/or constipation do not respond to bowel regimen or if unexplained diarrhea, weight loss/growth failure; also at-risk groups: type 1 diabetes,

autoimmune thyroiditis, Down/Turner syndrome Thyroid screen if abdominal pain/chronic constipation unresponsive to therapy ALERT H. pylori testing is not indicated in the evaluation of chronic/functional abdominal pain, nonulcer dyspepsia, or newly diagnosed GERD unless the patient has endoscopically documented peptic ulcer disease, a family history of gastric cancer, documented mucosa-associated lymphoid tissue (MALT) lymphoma, or unexplained iron deficiency anemia. Radiologic evaluation (abdominal decubitus and upright films) – Dilatation or air–fluid levels: acute obstruction – “Double bubble” sign and airless abdomen: midgut volvulus/malrotation – Air–fluid level or fecalith in right lower quadrant: acute appendicitis if suspected – Radiopaque renal stones or dilated ureters Upper gastrointestinal contrast study to document anatomic anomalies (i.e., malrotation) Ultrasound/CT scan in the evaluation of trauma, acute appendicitis, intussusception, suspected abscess in IBD, tumors, pancreatitis/pseudocyst, cholecystitis Use of CT scan in suspected acute appendicitis should be carefully considered, as it can both lead to unnecessary appendectomies or be falsely negative. In patients identified as “low risk” for appendicitis (absent leukocytosis with left shift), ultrasound and/or close observation should be considered as alternative to CT scan.

TREATMENT GENERAL MEASURES In the acute setting of abdominal pain suggesting a potential life-threatening condition (acute appendicitis, acute obstruction, volvulus), the patient should be stabilized and referred appropriately for further management including surgery if indicated. In the setting of extraintestinal conditions (i.e., pneumonia, pharyngitis, or urinary tract infection), antibiotic therapy should be initiated if indicated. In the setting of chronic pain and in the absence of red flags (see “Issues for Referral”), diagnosis most likely falls into abdominal pain—related FGIDs. These include functional dyspepsia, IBS, abdominal migraine, and functional abdominal pain not otherwise specified. The diagnosis of these entities is based on specific symptom-based criteria (Rome IV). Functional dyspepsia: trial of proton pump inhibitor (PPI) therapy for 4 weeks to rule out postviral dyspepsia. Avoid use of NSAIDs, spicy and fatty foods, and caffeine. If no response or unable to tolerate progressive taper of PPIs, refer to a gastroenterologist for endoscopic evaluation. Irritable bowel syndrome: Address bowel pattern: diarrhea (antidiarrheals); constipation (nonstimulating laxatives); peppermint oil or antispasmodics may alleviate pain Functional abdominal pain: Use biopsychosocial approach; behavioral treatment with or without trial of tricyclic antidepressants or SSRIs (particularly in presence of anxiety) ALERT

Psychological comorbidities should be addressed in all FGIDs. ISSUES FOR REFERRAL The presence of clinical red flags, in the setting of acute or chronic abdominal pain, may indicate an underlying mucosal pathology of the gastrointestinal tract (other than infectious), warranting referral to a gastroenterologist for further endoscopic evaluation and management. These include the following: Nocturnal pain: pain that wakes from sleep Persistent vomiting and/or dysphagia GERD nonresponsive to PPI trial Hematemesis Nocturnal diarrhea Hematochezia Perianal disease Weight loss/delayed growth and/or puberty Family history of PUD or IBD

ADDITIONAL READING Chitkara DK, Rawat DJ, Talley NJ. The epidemiology of childhood recurrent abdominal pain in Western countries: a systematic review. Am J Gastroenterol. 2005;100(8):1868–1875. Hyams JS, Di Lorenzo C, Saps M, et al. Functional disorders: children and adolescents [published online ahead of print February 15, 2016]. Gastroenterology. doi:10.1053/j.gastro.2016.02.015. Jones NL, Koletzko S, Goodman KJ, et al. Joint ESPGHAN/NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (Update 2016). J Pediatr Gastroenterol Nutr. 2017;64(6):991–1003. Kharbanda AB, Dudley NC, Bajaj L, et al; for Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Validation and refinement of a prediction rule to identify children at low risk for acute appendicitis. Arch Pediatr Adolesc Med. 2012;166(8):738–744. Koppen IJ, Nurko S, Saps M, et al. The pediatric Rome IV criteria: what’s new? Expert Rev Gastroenterology Hepatol. 2017;11(3):193–201. Korterink JJ, Ockeloen L, Benninga MA, et al. Probiotics for childhood functional gastrointestinal disorders: a systematic review and meta-analysis. Acta Paediatr. 2014;103(4):365–372. Newlove-Delgado TV, Martin AE, Abbott RA, et al. Dietary interventions for recurrent abdominal pain in childhood. Cochrane Database Syst Rev. 2017;(3):CD010972. Ross A, LeLeiko NS. Acute abdominal pain. Pediatr Rev. 2010;31(4):135–144. Saps M, Youssef N, Miranda A, et al. Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional abdominal gastrointestinal disorders. Gastroenterology. 2009;137(4):1261– 1269.

CODES ICD10 R10.9 Unspecified abdominal pain

R10.0 Acute abdomen R10.31 Right lower quadrant pain

ABNORMAL BLEEDING Char M. Witmer, MD, MSCE

BASICS DESCRIPTION Abnormal bleeding may present as Frequent or significant mucocutaneous bleeding (epistaxis, bruising, gum bleeding, or menorrhagia) Bleeding in unusual sites such as muscles, joints, or internal organs Excessive postsurgical bleeding ETIOLOGY Abnormal bleeding can be the result of a coagulation factor deficiency, an acquired or congenital disorder of platelet number or function, or inherited or acquired collagen vascular disorders.

DIAGNOSIS Approach to patient Phase 1 – Includes a thorough history and physical exam – Familial history specifically of bleeding or consanguinity – Standard screening laboratory tests include PT, aPTT, and platelet count. Phase 2 – If a bleeding disorder is suspected but the initial screening tests are negative, testing for von Willebrand disease, qualitative platelet disorders, dysfibrinogenemia, or factor XIII deficiency is warranted. Phase 3 – Any abnormal screening tests need further evaluation with additional testing to define the specific disorder (e.g., factor assays). HISTORY By taking into account the patient’s age, sex, clinical presentation, past medical history, and family history, the most likely cause of bleeding can be usually determined. Hemophilia is X-linked, most common in males. A family history of bleeding suggests an inherited bleeding disorder. Bleeding in unusual places without significant trauma (intracranial, joints) indicates a significant bleeding disorder. Persistent palpable bruising is highly suggestive of a bleeding disorder. Several surgeries without bleeding makes an inherited bleeding disorder less likely. Mucocutaneous bleeding (gum bleeding, bruises, epistaxis, recurrent petechiae, menorrhagia) may indicate thrombocytopenia, a platelet disorder, or von Willebrand disease.

The use of aspirin and NSAIDs (e.g., ibuprofen) negatively affect platelet function and result in an acquired bleeding disorder. Some congenital syndromes may have accompanying bleeding diathesis, which may be unrecognized until they face a hemostatic challenge. PHYSICAL EXAM Children with bleeding disorders are more likely to have large bruises (>5 cm), palpable bruises, and bruises on more than one body part. Uncommon sites for bruising for all ages include the back, buttocks, arms, and abdomen. Finding: Petechiae in skin and mucous membranes? Significance: disorder of platelet number or function, von Willebrand disease, or vasculitis Finding: Bruises in unusual places? Significance: possible platelet disorder, von Willebrand disease, or coagulation deficiency Finding: Large bruises or palpable bruises? Significance: coagulation deficiencies, severe platelet disorders, or von Willebrand disease Finding: Delayed wound healing? Significance: factor XIII deficiency or dysfibrinogenemia Finding: Purpura localized to lower body (buttocks, legs, ankles)? Significance: Henoch-Schönlein purpura DIFFERENTIAL DIAGNOSIS Platelet disorders may be quantitative or qualitative, collagen vascular disorders can be acquired or inherited, and disorders of coagulation factors can be congenital or acquired. Thrombocytopenia: defective production – Congenital/genetic Thrombocytopenia with absent radii syndrome Amegakaryocytic thrombocytopenia Fanconi anemia Metabolic disorders Wiskott-Aldrich syndrome Bernard-Soulier syndrome Other rare familial syndromes (e.g., MYH9-related disorders, RUNX1 mutations) – Acquired Aplastic anemia Drug-associated marrow suppression Virus-associated marrow suppression Chemotherapy Radiation injury Nutritional deficiencies (e.g., vitamin B12 and folate) – Marrow infiltration Neoplasia (e.g., leukemia, solid tumor) Histiocytosis

Osteopetrosis Myelofibrosis Hemophagocytic syndromes Storage diseases Thrombocytopenia: increased destruction – Idiopathic thrombocytopenia – Neonatal alloimmune thrombocytopenia – Maternal autoimmune thrombocytopenia – Drug-induced (heparin, sulfonamides, digoxin, chloroquine) – Disseminated intravascular coagulation – Infection: viral, bacterial, fungal, rickettsial – Microangiopathic process (e.g., thrombotic thrombocytopenic purpura or hemolytic uremic syndrome) – Kasabach-Merritt syndrome Thrombocytopenia: sequestration – Hypersplenism – Hypothermia Platelet function disorders – Storage pool disorders (e.g., dense granule deficiency, Hermansky-Pudlak or Chédiak-Higashi syndrome) – Platelet receptor abnormalities (e.g., Glanzmann thrombasthenia, adenosine 5′-diphosphate receptor defect) – Drugs (e.g., aspirin, NSAIDs, guaifenesin, antihistamines, phenothiazines, anticonvulsants) – Uremia – Paraproteinemia Coagulation disorders – Prolongation of activated partial thromboplastin time (aPTT) Deficiency of factors VIII, IX, XI, or XII; prekallikrein; or high-molecular-weight kininogen Acquired inhibitor or lupus anticoagulant – Prolongation of prothrombin time (PT) Deficiency of factor VII Mild vitamin K deficiency Liver disease, mild to moderate – Prolongation of PT and aPTT Deficiency of factors II, V, or X or fibrinogen Liver disease, severe Disseminated intravascular coagulation Severe vitamin K deficiency Hemorrhagic disease of the newborn Dysfibrinogenemia Hypoprothrombinemia associated with a lupus anticoagulant

– Normal screening (PT, aPTT) laboratory tests Von Willebrand disease Factor XIII deficiency α2-Antiplasmin deficiency Plasminogen activator inhibitor-1 deficiency Vessel wall disorders – Congenital Hereditary hemorrhagic telangiectasia Ehlers-Danlos syndrome Marfan syndrome – Acquired Vasculitis (systemic lupus erythematosus, Henoch-Schönlein purpura, and others) Scurvy (vitamin C deficiency) ALERT Always consider nonaccidental injury as a cause of increased bruising. DIAGNOSTIC TESTS & INTERPRETATION Phase 1: initial laboratory screening – Platelet count – PT and aPTT Phase 2: test for von Willebrand disease – Factor VIII:C – Von Willebrand factor antigen (VIIIR:Ag) – Von Willebrand factor activity (ristocetin cofactor) – Von Willebrand factor multimeric analysis—only send after the diagnosis of von Willebrand disease has been established – Thrombin time and fibrinogen assay to screen for afibrinogenemia and dysfibrinogenemia – Definitive platelet testing includes platelet aggregation and secretion studies with specific agonists. – Factor XIII deficiency suspected: factor XIII assay (Urea clot lysis study is a screening test.) Phase 3: discriminating laboratory studies for abnormal phase 1 or 2 tests The aPTT may be extremely prolonged in patients with deficiencies of the contact factors (prekallikrein, high-molecular-weight kininogen, factor XII). These deficiencies do not result in bleeding. Improper specimen collection including heparin contamination or underfilling of the specimen tube can result in artificially prolonged clotting times. When thrombocytopenia is present: – Inspection of blood smear – Mean platelet volume (may be normal or elevated in destructive causes, elevated in congenital macrothrombocytopenias, low in Wiskott-Aldrich syndrome) – Bone marrow aspiration (rarely necessary) Prolonged aPTT

– Inhibitor screen (50:50 mixing study of patient’s and normal plasma) – If aPTT fully corrects with mixing, this is consistent with a factor deficiency: Assess for specific factor deficiencies: factors VIII, IX, XI, or XII; prekallikrein; and highmolecular-weight kininogen – If partial or no correction after mixing study: Inhibitor is present. Confirmatory test for the presence of a lupus anticoagulant with a platelet-neutralizing procedure or dilute Russell viper venom time (DRVVT) Prolonged PT – Inhibitor screen should also be considered for prolonged PT. – Specific factor level (VII) Prolonged PT and aPTT – Factor assays: II (prothrombin), V, X, and fibrinogen – Potential other causes: disseminated intravascular coagulation, liver disease, and fibrinogen disorders, as described previously – Vitamin K deficiency, moderate to severe ALERT Pitfalls of testing: Platelet Function Assay (PFA)-100 – Low specificity and sensitivity – Affected by medications (NSAIDs) – Not recommended as a screening test Bleeding time – Prolonged when platelets 5 cm), palpable (raised) bruises, and bruises on more than one body part. Uncommon sites for bruising for all ages include the back, buttocks, arms, and abdomen.

ACETAMINOPHEN (PARACETAMOL) POISONING Kevin C. Osterhoudt, MD, MS

BASICS DESCRIPTION Acetaminophen poisoning may occur after acute or chronic overdose. Acetaminophen is sold under many brand names and is often an ingredient in combination pain reliever preparations. Acetaminophen poisoning may be clinically occult until frank hepatic or renal injury becomes evident. After acute overdose, a serum acetaminophen level above the treatment line of the Rumack-Matthew acetaminophen poisoning nomogram should be considered possibly hepatotoxic. Serious hepatotoxicity after a single acute exploratory ingestion by young children is rare compared with that from intentional overdose by adolescents. Most toddlers with acetaminophen hepatotoxicity suffer from repeated supratherapeutic dosing. EPIDEMIOLOGY Analgesics are the most common drugs implicated in poisoning exposures reported to United States poison control centers. Acetaminophen preparations make up ~45% of all analgesic poisoning exposures reported to poison control centers. Acetaminophen poisoning is the most common cause of acute liver failure in the United States. RISK FACTORS Depression Pain syndromes Glutathione depletion: prolonged vomiting, alcoholism, etc. CYP2E1 induction (e.g., alcoholism, isoniazid therapy) GENERAL PREVENTION Acetaminophen should be stored with child-resistant caps, out of sight of young children. Proper use of acetaminophen products should be taught to patients with pain or fever. PATHOPHYSIOLOGY Most absorbed acetaminophen is metabolized through formation of hepatic glucuronide and sulfate conjugates. Some acetaminophen is metabolized by the CYP450 mixed-function oxidase system, leading to the formation of the toxic N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI is quickly detoxified by glutathione under usual circumstances. After overdose, metabolic detoxification can become saturated: – Drug elimination half-life becomes prolonged. – More NAPQI is produced.

– Glutathione supply cannot meet detoxification demand. – Hepatic or renal toxicity may ensue. ETIOLOGY Single acute overdose of >200 mg/kg or 10 g Repeated overdose of >150 mg/kg/24 h or 6 g/24 h, for >2 days (or >100 mg/kg/24 h or 4 g/24 h if “susceptible”) COMMONLY ASSOCIATED CONDITIONS Acetaminophen is often marketed in combination with other pharmaceuticals, which may complicate a drug overdose situation. Adolescents frequently overdose on >1 drug preparation.

DIAGNOSIS HISTORY Medical history of pain or fever – Acetaminophen ingestion should be explored in any patient being treated for pain or fever. Amount of acetaminophen ingested – A single, acute ingestion of 4 hours after overdose falls above the treatment line of the Rumack-Matthew nomogram (see Appendix, Figure 4). – Patients presenting to medical care >7 hours after overdose should be given a loading dose of Nacetylcysteine while waiting for the serum acetaminophen level result. – IV N-acetylcysteine dose: 150 mg/kg (maximum 15 g) loading dose over 1 hour, then 12.5 mg/kg/h for 4 hours (maximum 5 g over 4 h), and then 6.25 mg/kg/h for 16 hours (maximum 10 g over 16 h) (see “FAQ”) ALERT Some toxicologists suggest higher N-acetylcysteine dosing for very large acetaminophen overdoses. Please contact an expert for a serum acetaminophen concentration >400 mcg/mL or for evidence of mitochondrial failure. – Oral N-acetylcysteine dose: 140 mg/kg (maximum 15 g) loading dose, followed by 70 mg/kg (maximum 7.5 g) maintenance doses q4h (see “FAQ”) Repeated supratherapeutic ingestion

– Consider N-acetylcysteine therapy if Ingestion of >150 mg/kg or 6 g/24 h for consecutive days Patient is symptomatic. Serum AST concentration is elevated. Acetaminophen level is higher than would be expected given dosing, and AST level is normal. Once started, N-acetylcysteine therapy should be continued until – The serum acetaminophen level is nondetectable – A simultaneous serum AST has not risen or, if elevated, liver enzymes and liver function are clearly improving Precautions – IV N-acetylcysteine has been associated with anaphylactoid reactions, which may require cessation or slowing of infusion, antihistamines, corticosteroids, and/or epinephrine. – Acetaminophen poisoning and oral N-acetylcysteine are emetogenic: Chill and cover the Nacetylcysteine. Consider antiemetic therapy or slow nasogastric administration if necessary. ISSUES FOR REFERRAL Patients with AST approaching 1,000 IU/L should be considered for transfer to a liver transplant center. Mental health services should be provided to victims of intentional overdose. SURGERY/OTHER PROCEDURES Liver transplant should be considered per transplant center protocols. The King’s College Hospital Criteria include the following: pH 1.8 times control, plus Serum creatinine >3.3 mg/dL, plus Encephalopathy ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS Admission criteria – N-acetylcysteine therapy – Psychiatric evaluation warranted Discharge criteria – N-acetylcysteine therapy concluded – No concern for developing liver injury

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patient Monitoring Cardiorespiratory monitoring is warranted during IV N-acetylcysteine therapy. Intensive care monitoring is warranted during fulminant hepatic failure. PATIENT EDUCATION

Drug administration education should be offered to victims of chronic overdose. Home safety education should be provided after pediatric exploratory ingestions. PROGNOSIS Among previously healthy children, hepatotoxicity is rare with single doses 99% of acetaminophen-poisoned patients if administered within 8 hours of overdose. N-Acetylcysteine therapy is less efficacious when administered >8 hours after overdose but should still be offered. Repetitive dosing of acetaminophen >75 mg/kg/24 h should be evaluated cautiously, especially in the presence of the following: – Febrile illness – Vomiting or malnourishment – Anticonvulsant or isoniazid therapy COMPLICATIONS Hepatic failure Renal insufficiency Anaphylactoid shock may complicate IV N-acetylcysteine therapy.

ADDITIONAL READING American College of Medical Toxicology. ACMT position statement: duration of intravenous acetylcysteine therapy following acetaminophen overdose. J Med Toxicol. 2017;13(1):126–127. Chun LJ, Tong MJ, Busuttil RW, et al. Acetaminophen hepatotoxicity and acute liver failure. J Clin Gastroenterol. 2009;43(4):342–349. Dart RC, Erdman AR, Olson KR, et al; for American Association of Poison Control Centers. Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2006;44(1):1–18. Heard KJ. Acetylcysteine for acetaminophen poisoning. New Engl J Med. 2008;359(3):285–292. Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol. 2012;50(2):91–98.

CODES ICD10 T39.1X4A Poisoning by 4-Aminophenol derivatives, undetermined, init K71.9 Toxic liver disease, unspecified T39.1X1A Poisoning by 4-Aminophenol derivatives, accidental, init

FAQ

Q: What is “patient-tailored” N-acetylcysteine therapy? A: The duration of N-acetylcysteine therapy used to depend on the pharmaceutical form administered but is now tailored to the patient based on serum acetaminophen level and liver function. Q: Should N-acetylcysteine be given PO or IV? A: Both seem to be similarly efficacious. Oral administration of N-acetylcysteine is complicated by taste aversion and vomiting. IV N-acetylcysteine may lead to anaphylactoid shock. Few cost–benefit studies are available for direct comparison of patient-tailored courses of oral N-acetylcysteine and IV N-acetylcysteine.

ACNE Deepti Gupta, MD Renee M. Howard, MD

BASICS DESCRIPTION Acne vulgaris is one of the most common skin conditions in children and adolescents. It is a disorder of pilosebaceous units (PSUs). PSUs are found predominantly on the face, chest, back, and upper arms. Acne presents as comedonal or inflammatory lesions and can cause depressed scars and hyperpigmentation. Presentation, treatment, and associated systemic manifestations differ by age of presentation, pubertal status, and severity of disease. Classification of acne by age: – Neonatal (birth to 6 weeks): affects up to 20% of neonates. Also known as neonatal cephalic pustulosis. Presents with a papulopustular eruption predominantly on face. Thought to be due to Malassezia colonization. No treatment necessary; for severe cases can use ketoconazole cream 2% – Infantile acne (6 weeks to 1 year): presents with comedonal and inflammatory lesions on face. Some evidence that it may predispose to severe adolescent acne. Often, no underlying endocrine abnormality; self-limited but in severe cases can use topical acne treatments – Midchildhood acne (1 to 6 years): uncommon. Presents with comedonal and inflammatory lesions on face. Suspect an underlying endocrinopathy. – Preadolescent (7 to 11 years): presents with predominantly comedonal lesions in “T-zone,” central face; can be first sign of onset of puberty – Adolescent (12 to 19 years): very common presentation, affects 85% of adolescents RISK FACTORS Genetics Familial patterns exist, but no inheritance pattern has been demonstrated. GENERAL PREVENTION Effective and early treatment limits scarring, postinflammatory pigment alteration, and minimizes psychosocial impact. Use of oil-free and noncomedogenic moisturizers, sunscreens, and make-up PATHOPHYSIOLOGY Pathogenesis of acne is multifactorial and involves four different components: Increased sebum production: stimulated by an increase in androgen levels. The adrenal gland is active during the 1st year of life and then reawakens in preadolescent time period. Production peaks in teens and decreases in 20s. Alteration in follicular growth and differentiation leading to the creation of a microcomedone, a precursor of inflammatory and comedonal acne lesions Follicular colonization with Propionibacterium acnes, an anaerobic, gram-positive diphtheroid bacteria. P. acnes produces free fatty acids (FFAs) leading to inflammation.

Inflammation and immune response through the innate immune system ETIOLOGY Androgen excess (physiologic vs. pathologic) Medication-induced (corticosteroids, anticonvulsants, lithium, etc.) Occlusion (from topical- or oil-based products) Frictions from clothing or athletic gear such as helmets, shoulder pads, chin straps, or bra straps may worsen acne. COMMONLY ASSOCIATED CONDITIONS Polycystic ovarian syndrome (PCOS) SAPHO syndrome: synovitis, acne, pustulosis, hyperostosis, and osteitis Adrenal or gonadal/ovarian tumors Late-onset congenital adrenal hyperplasia

DIAGNOSIS HISTORY Age of onset: Early or late onset of acne may indicate androgen excess. Medications and supplement use: Hormonal (including some oral contraceptive products (OCPs), progestin implants, depot medroxyprogesterone), steroids (topical, inhaled, or oral), anticonvulsants (lithium, isoniazid, nicotine products) may worsen acne. Menstrual history: Premenstrual flares may occur due to androgenic effects of progesterone. Androgen excess (history of or current): – Prepubertal: early-onset acne or body odor, increased linear growth, axillary or pubic hair, genital maturation, or clitoromegaly – Postpubertal: alopecia, hirsutism, truncal obesity, acanthosis nigricans, irregular menses, increased muscle mass Previous acne treatments tried, effect of previous treatments, and reason treatment failed (cost, adherence, tolerability, ease of use) ALERT Psychological impact: Ask patients about self-esteem, depression, and suicidal ideations. PHYSICAL EXAM Skin – Distribution of lesions – Type of acne lesions: comedonal (open: blackhead, due to oxidation of lipids and not dirt; closed: whitehead), inflammatory (erythematous papule, pustule, nodule, pseudocyst) – Scarring and hyperpigmentation Global assessment of acne severity (number, size, extent, and scarring) Note signs of androgen excess (see “History”). Height, weight, growth curve

Blood pressure DIFFERENTIAL DIAGNOSIS Adenoma sebaceum (facial angiofibromas) Keratosis pilaris Flat warts Molluscum contagiosum Periorificial dermatitis Milia Miliaria Syringomas Demodex folliculitis Malassezia (Pityrosporum) folliculitis Gram-negative folliculitis Staphylococcal folliculitis Chloracne (exposure to chlorinated aromatic hydrocarbons) Papular sarcoidosis DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Consider for patients with signs of androgen excess, midchildhood acne, or acne unresponsive to traditional therapy. – Serologic testing (LH, FSH, testosterone total and free, dehydroepiandrosterone sulfate (DHEA-S), androstenedione prolactin, 17-hydroxyprogesterone) – Bone age – Referral to pediatric endocrinology – Imaging for adrenal or gonadal tumor Lab monitoring while using isotretinoin should include baseline complete blood count (CBC), fasting lipid panel (triglycerides and cholesterol), transaminases, and pregnancy test for females and monthly fasting lipid panel (triglycerides and cholesterol), transaminases, and pregnancy test for females. Prior to starting, females need two negative pregnancy tests 30 or more days apart.

TREATMENT Choose regimen based on previous therapies used and effect, cost, vehicle selection, regimen complexity, active scarring, and psychosocial impact. Vehicle selection: – Creams and lotions less drying than gels and solutions – Creams better for sensitive skin/eczema – Gels and solutions may be better for oily skin or for use with make-up. Manage patient expectations. Treatment may take 2 to 3 months to be effective.

Acne may initially flare prior to improving. Counsel about medication side effects. General approach: categorized by acne severity and age of patient – Mild acne: comedonal, inflammatory, or mixed Initial: ■ Topical monotherapy: Benzoyl peroxide (BP) Topical retinoid ■ Topical combination therapy: BP + antibiotic Retinoid + BP Retinoid + BP + antibiotic Inadequate response: ■ Assess adherence. ■ Add BP or retinoid if not already prescribed. ■ Change: Topical retinoid concentration, type, or formulation Change topical combination therapy. – Moderate acne: comedonal, inflammatory, or mixed Initial: ■ Topical combination therapy: Retinoid + BP Retinoid + BP + antibiotic ■ Oral antibiotic + topical retinoid + BP Inadequate response: ■ Assess adherence. ■ Change topical retinoid concentration, type, or formulation. ■ Add or change oral antibiotic. ■ Females: Consider hormonal therapy. ■ Consider oral isotretinoin. ■ Consider dermatology referral. – Severe acne: inflammatory, mixed, and/or nodular lesions; extensive involvement often with significant scarring Initial: ■ Oral antibiotic + topical retinoid + BP ± topical antibiotic ■ Consider oral isotretinoin. ■ Consider dermatology referral. Inadequate response: ■ Assess adherence. ■ Change topical retinoid concentration, type, or formulation. ■ Change oral antibiotic.

■ Females: Consider hormonal therapy. ■ Consider oral isotretinoin. ■ Scars warrant aggressive treatment targeting inflammation. MEDICATION Topical agents/over the counter – Gentle cleansers: Using gentle soap-free, pH-balanced cleansers is recommended for everyday washing. BP: ■ Bactericidal, mild comedolytic, and anti-inflammatory properties ■ Limits antibiotic resistance and provides increased efficacy in combination with retinoids ■ Available as lotion, cream, wash, and gel in 2.5–10% ■ Increased concentration does not increase efficacy but can cause more irritation. ■ 5% concentration generally effective; can start with lower concentration or decrease number of days of use if too irritating ■ Side effects: drying, erythema, burning, peeling, stinging, and rarely contact dermatitis ■ Cautions: can cause bleaching of hair, clothing, and linen; increased risk of photosensitivity; rare but serious and potentially life-threatening allergic reactions or severe irritation have been reported. Salicylic acid (SA): ■ Promotes comedolysis with drying and peeling ■ Not as effective as BP Sulfur/sulfacetamide: ■ Mild antibacterial and keratolytic properties ■ Very well-tolerated ■ Distinctive odor ALERT Avoid vigorous cleansing of the skin or harsh facial astringents and toners that may irritate the skin. Prescription topical medications – Topical antibiotics (erythromycin, clindamycin): Reduce P. acnes concentration and inflammatory mediators Available in combination products to increase compliance, but these products are often more expensive Combine with BP to decrease antibiotic resistance Combine with retinoids to help yield faster results Side effects: well-tolerated but may include drying or irritation – Topical retinoids: Prevent formation of microcomedones, clear existing microcomedones, anti-inflammatory Available in three forms Adapalene ■ Available as cream or gel and as a combination product with BP

■ Pregnancy class C (see Appendix IV; Table 10) ■ Photostable ■ Better tolerability than tretinoin but weaker in strength Tretinoin ■ Available as cream, gel, microsphere gel of various strengths ■ Pregnancy class C (see Appendix IV; Table 10) ■ Apply to dry skin. ■ Apply pea-sized amount to entire face. ■ Can be very irritating and drying ■ Start with low concentration (0.025%) and decreased frequency (few times a week) of application and titrate up as tolerated. ■ Inactivated by sunlight; use at nighttime. ALERT BP inactivates tretinoin when used together. Apply BP in the morning and tretinoin at night. Tazarotene ■ Available in cream and gel ■ Pregnancy class X; contraindicated in pregnancy ■ Apply to dry skin. ■ More irritating than other retinoids ■ Inactivated by sunlight; use at nighttime. ■ Not 1st-line therapy for most patients ■ Side effects: erythema, dryness, irritation, initially acne flares, and photosensitivity (Advise use of daily noncomedogenic sunscreen with sun protection factor (SPF) 30+ and facial moisturizer tazarotene.) ■ Apply pea-sized amount to entire face. ■ Start with lowest strength 3 times a week and increase frequency slowly to every night as tolerated. Some patients may not tolerate medication every night. ■ Increase concentration of medication if patient still with oily skin or getting new acne lesions. – Azelaic acid: Comedolytic and antibacterial; decreases hyperpigmentation 15% gel or 20% cream, applied twice daily Pregnancy class B (see Appendix IV; Table 10) Side effects include itching, burning, stinging, and erythema. Consider for patients with comedonal acne who cannot use retinoids. – Topical dapsone: Synthetic sulfone has antimicrobial and anti-inflammatory effects. Available in 5% gel, twice-daily application recommended Most effective against inflammatory acne lesions Safe in patients with G6PD deficiency Enhanced efficacy when combined with retinoids Side effects: erythema and dryness

Caution: When used with BP, a temporary orange staining of skin can occur. ALERT Do not use antibiotics as monotherapy due to slow onset of action and development of antibiotic resistance. Use with BP. Oral antibiotics: reduce P. acnes concentration and inflammatory mediators – Tetracyclines (doxycycline, minocycline, tetracycline): pregnancy class D; must be >8 years of age due to staining of tooth enamel Doxycycline and minocycline are preferred due to 1 to 2×/24 h dosing and greater follicular penetration. ■ Dosing: 50 to 100 mg daily or b.i.d. Tetracycline is cheap but has least efficacy. Increasing antibiotic resistance. Limit treatment length and do not use as monotherapy. Use with BP or topical retinoid. Taper or switch to topical retinoid monotherapy after 12 weeks and when patient is no longer getting new acne lesions. Systemic side effects and cautions: ■ Doxycycline: GI upset, vaginal candidiasis, pill esophagitis, photosensitivity (phototoxicity), benign intracranial hypertension; take with food and large glass of water, stay upright 1 hour after taking medication, photoprotection, can use enteric-coated form ■ Minocycline: acute vestibular reaction (vertigo, dizziness), vaginal candidiasis, hyperpigmentation, drug-induced hypersensitivity reaction 2 to 8 weeks after starting medication, lupus-like syndrome, autoimmune hepatitis, Stevens-Johnson syndrome (SJS), benign intracranial hypertension – Sulfa (trimethoprim-sulfamethoxazole): Dosing: 160 to 800 mg PO b.i.d. Used judiciously, refractory cases Systemic side effects: severe cutaneous reactions (SJS, toxic epidermal necrolysis, drug-induced hypersensitivity reaction, fixed drug eruption), bone marrow suppression Check baseline CBC and periodically thereafter. – Cephalosporins (cephalexin, cefadroxil): Dosing: 500 mg PO b.i.d. Well-tolerated Systemic side effects: GI upset – Penicillins (amoxicillin): Well-tolerated Systemic side effects: GI upset – Macrolides (erythromycin, azithromycin) High prevalence of P. acnes resistance to erythromycin Systemic side effects: erythromycin GI upset, drug–drug interactions Oral retinoids (isotretinoin): decreases sebum production, anti-inflammatory, and reduces P. acnes – Used as monotherapy

– Used for recalcitrant acne and/or with significant scarring – Dosing: Start with 0.5 mg/kg/24 h for first 4 weeks and then advance to 1 mg/kg/24 h. Goal cumulative treatment course is generally 120 to 150 mg/kg. Higher courses up to 220 mg/kg have been reported. For patients with severe inflammatory and nodulocystic acne, start at lower dose and consider starting oral corticosteroids to prevent acne fulminans. – Need baseline and monthly labs (see “Initial Tests (screening, lab, imaging)”) – Side effects: Common: dry skin, dry eyes, cheilitis, photosensitivity, myalgias Teratogen ■ Two forms of birth control need to be used while on medication or abstinence. ■ FDA-mandated registry (iPledge: see https://www.ipledgeprogram.com/); prescribed only by registered users Depression and suicide have been reported in patients on isotretinoin; counsel about this risk and assess if patient a candidate for medication. Inflammatory bowel disease: conflicting data. Association may exist but rare, and there are many confounding factors. Bone effects: conflicting data regarding increased risk of fractures and demineralization. Hyperostoses and premature epiphyseal closure are rare and uncommon side effects. Rare, sporadic reports of serious skin infections including erythema multiforme, SJS, and toxic epidermal necrolysis ALERT Do not use tetracycline antibiotics with oral retinoids due to risk of pseudotumor cerebri. Hormonal therapy: 2nd-line therapy for women; usually used in combination with other acne treatments – OCPs (for women): suppress ovarian androgen production – Can be used as an adjunct for females with moderate to severe acne not responding to topical retinoids – Three OCPs are FDA-approved for acne: Ethinyl estradiol (35 mcg) and norgestimate (≥15 years of age) Ethinyl estradiol (20–30–35 mcg) and norethindrone (≥15 years of age) Ethinyl estradiol (30 mcg) and drospirenone (3 mg) (≥14 years of age) – Screen for personal tobacco use and family history of thromboembolic event. Use caution in girls who smoke tobacco. – May need 3 to 6 months to see improvement – Side effects include nausea, breast tenderness, headache, weight gain, breakthrough menstrual bleeding, myocardial infarction, ischemic stroke, and deep venous thrombses. – Controversial effect on bone density and growth; recommendation to start at least 1 year after onset of menstruation Spironolactone (for women): a potassium-sparing diuretic; blocks androgen receptor in sebaceous glands reducing sebocyte proliferation

– Dose 25 to 150 mg daily start low and titrate to minimum effective dose. – Off-label use – Can be used in combination with OCP – Side effects: hyperkalemia (lab monitoring may be indicated in some cases), teratogen (controversial/limited studies in animal models; the American College of Obstetricians and Gynecologists [ACOG] recommends not using during pregnancy especially during the first trimester due to antiandrogenic effects), hypotension, dizziness, dry mouth COMPLEMENTARY & ALTERNATIVE THERAPIES Limited empiric studies on CAM and acne Randomized controlled trials of the following showed that they were not as effective as 5% BP but resulted in less skin irritation: – Tea tree oil: a mixture of terpenes and alcohols with antibiotic and antifungal properties; 5% solution may be effective in treating comedonal and inflammatory acne; may be associated with male gynecomastia – Gluconolactone 14% solution may be effective on comedonal and inflammatory acne.

ONGOING CARE PATIENT EDUCATION http://www.aad.org/dermatology-a-to-z/diseases-and-treatments/a–d/acne http://www.nlm.nih.gov/medlineplus/acne.html (handout in Spanish also available) https://pedsderm.net/for-patients-families/patient-handouts/#Anchor-Acne (handout and patient education video) COMPLICATIONS Scarring may be permanent. Hyperpigmentation: occurs more in dark-skinned individuals; self-resolves but may take months to years Self-esteem: acne severity correlated to social variables including embarrassment and lack of enjoyment in social activities among teenagers Patients with mild to moderate acne showed clinical depression and >5% suicidal ideation. Depression scores improve in correlation with response to acne treatment.

ADDITIONAL READING Eichenfield LF, Krakowski AC, Piggott C, et al; for American Acne and Rosacea Society. Evidencebased recommendations for the diagnosis and treatment of pediatric acne. Pediatrics. 2013;131(Suppl 3):163–186. Friedlander SF, Eichenfield LF, Fowler JF Jr, et al. Acne epidemiology and pathophysiology. Semin Cutan Med Surg. 2010;29(2)(Suppl 1):2–4. Lam C, Zaenglein A. Contraceptive use in acne. Clin Dermatol. 2014;32(4):502–515. Yan AC, Baldwin HE, Eichenfield LF, et al. Approach to pediatric acne treatment: an update. Semin

Cutan Med Surg. 2011;30(Suppl 3):S16–S21.

CODES ICD10 L70.9 Acne, unspecified L70.4 Infantile acne L70.0 Acne vulgaris

FAQ Q: Can I modify my diet to improve my acne? A: Limited and variable data is available. There is suggestion that high glycemic diets and skim milk consumption (not full-fat milk) may be associated with increased acne via activation of insulin and insulin-like growth factor 1 (IGF-1), which activates sebocyte production. Limited data is also available on the use of zinc and Nicomide supplementation and their potential to improve acne. Q: Does poor hygiene cause acne? A: No. Use of harsh astringents, exfoliating scrubs, and vigorous scrubbing can worsen acne by causing more inflammation and scarring. They also can be more irritating and drying, decreasing tolerability of acne treatments. Recommend use of a gentle, soap-free, pH-balanced cleanser for daily use in addition to noncomedogenic moisturizers and sunscreen in conjunction with acne treatments. Q: Do cosmetics worsen acne? A: Recommend use of oil-free, noncomedogenic make-up, which have been proven not to delay treatment response or worsen acne severity. Q: Any other factors that I should know about that can affect acne? A: Yes. Smoking also has shown to worsen acne through a mechanism of nicotinic acid binding to acetylcholine receptors and increasing follicular plugging and epithelial hyperplasia.

ACUTE DRUG WITHDRAWAL Robert J. Hoffman, MD, MS

BASICS DESCRIPTION Drug withdrawal is a physiologic response to an effectively lowered drug concentration in a patient with tolerance to that drug. Withdrawal results in a predictable pattern of symptoms that are reversible if the drug in question or another appropriate substitute is reintroduced. Sedative-hypnotic withdrawal is the most common life-threatening withdrawal syndrome in children. This includes withdrawal from barbiturates, benzodiazepines, baclofen, as well as γ-hydroxybutyrate and similar substances. Other substances that are associated with withdrawal syndromes include nicotine, opioids, selective serotonin reuptake inhibitors (SSRIs), and caffeine. EPIDEMIOLOGY The most common life-threatening withdrawal syndrome, alcohol withdrawal, rarely occurs in children. Neonates born to alcohol-dependent mothers are at risk. RISK FACTORS Patients receiving sedatives or analgesics capable of causing tolerance are at risk. Any inpatient use of sedative or opioids >5 days is a risk factor for withdrawal. This risk is particularly important to consider with infusions or high doses of such substances in previously naive patients. GENERAL PREVENTION Clinician familiarity with tolerance and withdrawal associated with prescribed medications allows appropriate drug tapering. Drug abuse prevention is appropriate for all children. PATHOPHYSIOLOGY Altered CNS neurochemistry is the most important and clinically relevant aspect of withdrawal pathophysiology. Under normal conditions, the CNS maintains a balance between excitation and inhibition. Although there are several ways to achieve this balance, excitation is constant and actions occur through removal of inhibitory tone. Relative to adults and younger children, adolescents are more prone to develop dependence and withdrawal syndrome due to immaturity of their prefrontal cortex. ETIOLOGY Neonates – Maternal alcohol, caffeine, opioid, sedative-hypnotic, or SSRI use may result in a neonatal

abstinence syndrome. – Treatment with caffeine, opioids, or sedative-hypnotics and subsequent discontinuation may result in subsequent development of an abstinence syndrome. Older children – Subsequent to treatment with opioids, or sedative-hypnotics, an abstinence syndrome may result. – Substance abuse, particularly opioids, γ-hydroxybutyrate, or other sedative-hypnotics, may result in an abstinence syndrome. – Frequent caffeine or nicotine use may lead to an abstinence syndrome. Use of opioid antagonists such as naloxone, naltrexone, and nalmefene is associated with development of opioid withdrawal.

DIAGNOSIS Drug withdrawal is a clinical diagnosis. Patients should be evaluated for associated diagnoses (e.g., traumatic injury, pneumonia). HISTORY Typically, a history of substance exposure, either direct exposure or maternal use, will be elicited. – Exposure may be to prescribed medication or abusable substances. – Substance use by the mother or child might intentionally be concealed. The timing of withdrawal varies depending on the half-life of the substance involved. – Shorter half-life causes quicker onset of withdrawal with greater severity. Alcohol or sedative-hypnotics – Causes tremor, diaphoresis, agitation, insomnia, altered mental status, or withdrawal seizures – Baclofen withdrawal is more frequently severe or life-threatening relative to benzodiazepine withdrawal. History of pump manipulation or malfunction should be sought. Caffeine – Withdrawal may result in dysphoria, headache, behavioral changes, or agitation. Opioids – Nausea, vomiting, diarrhea, irritability, yawning, sleeplessness, diaphoresis, lacrimation, tremor, and hypertonicity may result. – Neonates can also have seizures, a high-pitched cry, skin mottling, and excoriation. These latter signs and symptoms are more typical of opioid withdrawal and rarely occur with neonatal alcohol withdrawal. Nicotine – Dysphoria, agitation, behavioral changes, and increased appetite may all occur. SSRIs – Neonatal withdrawal from SSRIs may result in jitteriness, agitation, crying, shivering, increased muscle tone, breathing and sucking problems, as well as seizure. – Children withdrawing from SSRIs may have jitteriness, agitation, dysphoria, behavioral changes, shivering, increased muscle tone, and seizure.

PHYSICAL EXAM A clinically appropriate, validated scoring tool (e.g., Withdrawal Assessment Tool, Version 1 [WAT-1] for children or adolescents or the Finnegan Neonatal Abstinence Syndrome Scale for newborns) should be completed with the physical exam to obtain objective, valid assessment of severity of withdrawal. Vital signs including temperature should be evaluated regularly. Vital sign changes such as tachycardia and hypertension may occur concomitantly with acute drug withdrawal. Technology-dependent patients, such as children with an intrathecal baclofen pump, should have evaluation of the machine to determine if it is working properly. Most cases of substance withdrawal only result in behavioral changes. Opioid withdrawal may be accompanied by diaphoresis, mydriasis, yawning, and lacrimation. Sedative-hypnotic withdrawal may result in hypertension, tachycardia, hyperthermia, agitation, hallucinations, and seizure. DIFFERENTIAL DIAGNOSIS Hypoglycemia Intoxication with sympathomimetics, anticholinergics, theophylline, caffeine, aspirin, or lithium Thyroid storm Serotonin syndrome Neuroleptic malignant syndrome Encephalitis Meningitis Sepsis DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Neuroimaging to rule out intracranial pathology may rarely be indicated. Diagnostic Procedures/Other No routine lab tests are indicated for patients with substance withdrawal. Tests necessary to rule out differential diagnoses should be obtained when appropriate.

TREATMENT GENERAL MEASURES Initial stabilization – Initial management is aimed at evaluating and supporting airway, breathing, circulation, serum glucose, and ECG (“A, B, C, D, E”). Supportive care is the most important general principle. The illness is managed with intent of close monitoring and addressing issues as they arise. MEDICATION In adolescents and probably most children, symptom-triggered treatment is superior to fixed-regimen treatment in terms of patient outcome and length of stay.

For neonates, a standardized regimen of drug tapering appears to be superior with regard to shorter length of stay. Patients with benzodiazepines or barbiturate withdrawal may be treated by reinstituting the drug and then tapering. Iatrogenic withdrawal induced by use of opioid antagonists should not be treated by opioid administration. – Withdrawal induced by naloxone should abate rapidly due to the brief half-life of naloxone. – Withdrawal induced by naltrexone or nalmefene will be much longer lasting. Symptomatic treatment may be indicated. There is no fixed quantity of drug to use for any withdrawal syndrome. Each patient requires a unique quantity of drug, and use of 80% of the previous dosing is a useful rough estimate. – Repeated dosing should continue until the symptoms are controlled, at which point maintenance and then tapering can occur. Sedative-hypnotic withdrawal – Ideally, withdrawal is treated with the same class of substance, such as benzodiazepine or barbiturate, if not the precise same drug. – Benzodiazepines are particularly useful due to the rapid onset of effect. – Diazepam has active metabolites that may assist in tapering the drug in older children and neonates. – In neonates, diazepam efficacy is poor. – Lorazepam 0.1 mg/kg IV (maximum initial dose 4 mg) may be repeated q30min until symptoms have improved. – Propofol is an outstanding medication for treatment of severe alcohol or sedative-hypnotic withdrawal in adults. Propofol may be used in pediatric cases refractory to benzodiazepines and barbiturates. Use is associated with respiratory depression. Clinicians must be capable of airway management and expect airway support to be necessary when propofol is used. Propofol use is safe in children, but rare cases of metabolic acidemia have occurred when prolonged infusions are used. Prolonged use of propofol infusion should be accompanied by close observation for acidemia. Opioid withdrawal – Heroin (as well as other opioids) withdrawal is best treated with an opioid of similar potency and equal or longer duration of action. – Buprenorphine, which has been introduced to pediatric and neonatal practice recently, is extremely promising as therapy for opioid withdrawal. – Buprenorphine is a partial opioid agonist, does not cause respiratory depression, and does not result in the pleasurable or euphoric sensation associated with morphine or methadone. – Buprenorphine is currently only prescribable by specific clinicians with a special Drug Enforcement Agency (DEA) approval to give this therapy. – Methadone is currently a preferred treatment for withdrawal in adolescents and adults. – 5 to 10 mg of methadone empirically is an appropriate initial dose to treat adolescents and adults.

– For neonates, 0.05 mg/kg/dose PO or IV q6h with increase in dose by 0.05 mg/kg until symptoms are controlled, then the dosing interval can be increased to q12–24h – Patients who experience opioid withdrawal in the setting of chronic or intensive care may be treated by reinstituting infusion or dosing of the drug they were on before withdrawal symptoms and then tapering this, typically by 10% daily. Caffeine withdrawal – Caffeine as soft drink or tea taken to treat headache or agitation – Neonatal caffeine abstinence symptoms may be treated by reinstituting 75–100% of the caffeine dosage that was discontinued. This amount is then tapered, typically by 10% daily. Nicotine withdrawal is not typically treated in children. Use of nicotine patch, gum, or other delivery methods is used to increase success rate of abstinence rather than for medical management of the withdrawal syndrome. SSRI withdrawal in neonates may be treated with phenobarbital or a benzodiazepine such as diazepam or lorazepam. – Lorazepam dosing for SSRI withdrawal is 0.05 mg/kg IV q6h. – Phenobarbital dosing for SSRI withdrawal is 2.5 mg/kg/dose q12h. An optional loading dose either IV or PO may be used. – The quantity of SSRI excreted in breast milk varies between these medications, but generally, they are in breast milk in low quantities. – It is reasonable to permit or recommend breastfeeding for neonates experiencing SSRI withdrawal syndrome, despite medication instruction warnings to avoid breastfeeding. ISSUES FOR REFERRAL Any patient with substance abuse issues should be referred for appropriate psychiatric or drug counseling. Most cases of substance withdrawal are best handled by an addiction specialist, medical toxicologist, intensivist, or other clinician experienced with management of withdrawal. ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS Inpatient treatment for alcohol or sedative-hypnotic withdrawal is mandatory. Although withdrawal from opioids and SSRIs is not life-threatening, admission with initial management as an inpatient may be preferable. Maintenance IV fluid may be required in patients who are unable to take PO. Dehydration was once a leading cause of death among patients with alcohol withdrawal. Inpatients who have been converted from parenteral to oral medications and are controlled with oral medications may be discharged for home tapering. Patients who never require parenteral therapy may be discharged with oral replacement medication after consultation with the appropriate specialist.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS

If disposition will be discharge, it is crucial to ensure that the patient’s condition is stable before discharge. If there is any question regarding whether the patient can be appropriately managed as an outpatient, initial inpatient management is preferable. Patient Monitoring Sedative-hypnotic withdrawal or any other withdrawal syndrome with severe symptoms is best cared for with initial cardiopulmonary monitoring until vital sign abnormalities are controlled with appropriate replacement therapy. Patients should be closely monitored until vital signs are within acceptable limits. Vigilance for agitation or delirium with sedative-hypnotic withdrawal is necessary. Vigilance to detect oversedation and respiratory depression is necessary. PATIENT EDUCATION Patients or parents should be aware of withdrawal symptoms to be vigilant for detecting future events. PROGNOSIS With appropriate therapy, withdrawal is well tolerated. Poor prognostic factors are primarily related to comorbidities. COMPLICATIONS Complications of hypertension, tachycardia, hyperthermia, and CNS agitation or seizure may occur with sedative-hypnotic withdrawal.

ADDITIONAL READING Franck LS, Scoppettuolo LA, Wypij D, et al. Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain. 2012;153(1):142–148. Galinkin J, Koh JL; for Committee on Drugs, Section on Anesthesiology and Pain Medicine, American Academy of Pediatrics. Recognition of and management of iatrogenically induced opioid dependence and withdrawal in children. Pediatrics. 2014;133(1):152–155. Hall ES, Isemann BT, Wexelblatt SL, et al. A cohort comparison of buprenorphine versus methadone treatment for neonatal abstinence syndrome. J Pediatr. 2016;170:39–44.e1. McQueen K, Murphy-Oikonen J. Neonatal abstinence syndrome. N Engl J Med. 2016;375(25):2468– 2479. Nordeng H, Lindeman R, Perminov KV, et al. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr. 2001;90(3):288–291.

CODES ICD10 P96.1 Neonatal w/drawal symp from matern use of drugs of addiction P96.2 Withdrawal symptoms from therapeutic use of drugs in newborn

F13.939 Sedatv/hyp/anxiolytc use, unsp w withdrawal, unsp

ACUTE KIDNEY INJURY Stuart L. Goldstein, MD

BASICS DESCRIPTION Acute kidney injury (AKI) is defined as an abrupt (within 48 hours) reduction in kidney function with an absolute increase in serum creatinine of more than or equal to 0.3 mg/dL, or a 1.5-fold increase from baseline or a reduction in urine output (documented oliguria of 6 hours). In AKI, the urine output is variable: anuria, oliguria and, in some cases, polyuria can all be observed at presentation. EPIDEMIOLOGY The epidemiology of AKI has changed over the recent years from primary kidney disease to a syndrome secondary to other systemic illness. AKI may be seen in up to 10% of all hospitalized children. The incidence is higher in intensive care unit (ICU) admissions and with increasing multiorgan disease severity. AKI is seen in 27% of children admitted to an ICU. PATHOPHYSIOLOGY The pathogenesis of AKI is multifactorial. It may be initiated by ischemia or toxins, and the subsequent injury involves a complex interplay between vasoconstriction, leukostasis, vascular congestion, cell death, and abnormal immune modulators. ETIOLOGY Previously, AKI was subcategorized into three groups: prerenal, renal, and postrenal. The differentiation between “prerenal” and “intrinsic” causes can be difficult because renal hypoperfusion may coexist with any stage of AKI. For that reason “functional” has replaced prerenal and “structural” has replaced intrinsic in the terminology. Functional – Decreased glomerular filtration rate (GFR) resulting from renal hypoperfusion in a structurally intact kidney – Often rapidly reversible when the underlying cause is corrected Structural – Disorders that directly affect the kidney – Acute tubular necrosis (ATN) was used in the past to describe a form of intrinsic AKI from severe and persistent hypoperfusion of the kidneys. However, the histologic diagnosis of tubular necrosis is rarely confirmed by biopsy. – Glomerular disorders include the various forms of acute glomerulonephritis (AGN) (e.g., postinfectious, rapidly progressive [crescentic]). – Vascular lesions compromise glomerular blood flow. Hemolytic uremic syndrome (HUS) is the most common vascular disorder that causes intrinsic AKI in children.

– Acute interstitial nephritis (AIN) most often occurs as a result of exposure to medications such as NSAIDs. It may also be associated with infections (e.g., pyelonephritis), systemic diseases, or tumor infiltrates. Postrenal – Obstructive process (either structural or functional) – Obstruction can be in the lower tract or bilaterally in the upper tracts (unless the patient has a single kidney). – More common in newborns

DIAGNOSIS HISTORY Previous infection, neurogenic bladder, single kidney Exposure to nonsteroidal anti-inflammatory agents, β-lactam antibiotics, acyclovir, aminoglycosides, amphotericin B, cisplatin Gross hematuria: AGN (tea colored), renal calculi (bright red blood) Trauma: crush injury Signs and symptoms: fever, rash bloody diarrhea, pallor, severe vomiting or diarrhea, abdominal pain hemorrhage, shock, anuria, polyuria PHYSICAL EXAM General: weight and hydration status; shock, edema (calculation of percent fluid overload based on body weight), jaundice Lungs: rales Heart: gallop Abdomen/pelvis: mass Skin: rash, petechiae Joints: arthritis DIFFERENTIAL DIAGNOSIS Chronic kidney disease: insidious, associated with poor growth, normocytic anemia, hyperparathyroidism Azotemia (elevated BUN): hypercatabolic states including corticosteroid therapy or upper GI bleeding Elevated creatinine: caused by rhabdomyolysis, drugs (trimethoprim-sulfamethoxazole, cimetidine) DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) All patients with AKI should have a urinalysis with microscopic exam, serum chemistries, and a CBC: – Urinalysis: specific gravity (>1.020 suggests prerenal AKI), proteinuria (>3+ structural, glomerular AKI), eosinophiluria (AIN), pyuria (pyelonephritis), granular casts (functional, ATN), pigmenturia (ATN), erythrocyte casts (glomerulonephritis, AIN, ATN) – Serum chemistries: hyponatremia, acidosis, hyperkalemia, hypocalcemia, hyperphosphatemia

– CBC: microangiopathic hemolytic anemia, thrombocytopenia (i.e., HUS), eosinophilia (i.e., AIN) – Selected patients require further studies, including serologies, urine electrolytes, imaging, and renal biopsy: Serologies: hypocomplementemia, antineutrophil cytoplasmic antibodies, antinuclear antibodies (AGN) Fractional excretion of sodium (FENa) – Can be useful to assess tubular function; FENa = [(UNa / PNa) / (Ucreat / Pcreat)] × 100 – The FENa should not be obtained after diuretics are administered; FENa >2: ATN; FENa 1.5 in presence of encephalopathy or INR >2 without encephalopathy In older children, in whom hepatic encephalopathy can be more easily assessed, ALF may more simply be defined as follows: – Onset of encephalopathy 90% of alcohol is consumed through binge drinking (>5 drinks for males or >4 drinks for females); prevalence of binge alcohol use in past 2 weeks in 2012 was 5% of 8th graders, 16% of 10th graders, 24% of 12th graders, 37% of college students, and 36% of young adults. Among college students, 20% of males and 8% of females report having consumed double the binge threshold (>10 drinks for males and >8 for females). 24% of high school students have ridden in a car driven by someone who had been drinking alcohol; 8% had driven a car when they had been drinking. 56% of college students mixed energy drinks with alcohol in the past month. Household products (medicinal, cosmetic, cleaning, hygiene) can contain up to 100% ethanol; rates of accidental exposure to and intentional intoxication from hand sanitizers are increasing. RISK FACTORS Patients with psychiatric conditions are at an increased risk for abuse of alcohol and other drugs. GENERAL PREVENTION

Promote family discussions about alcohol use and abuse. Provide safety recommendations to prevent accidental ingestions. PATHOPHYSIOLOGY Effects of alcohol ingestion are related to dose, the time in which alcohol was consumed and then absorbed, and the patient’s history of alcohol exposure; peak serum concentrations occur 30 to 60 minutes after ingestion. Alcohol absorption, decreased by the presence of food in the stomach and increased if liquid is carbonated, occurs rapidly and largely in the small intestine. – Minimal quantities of alcohol are excreted in urine, sweat, and breath. – >90% of alcohol oxidized in liver follow zero-order kinetics, primarily by alcohol dehydrogenase (ADH) and then acetaldehyde dehydrogenase (ALDH). – Rate of metabolism is fixed (not related to dose or time) and is proportional to body weight. – Ethnic/racial and gender variabilities exist on quantity and efficacy of ADH. – Ethanol is metabolized by ADH to acetaldehyde, then to acetate, and finally to ketones, fatty acids, or acetone; ketosis and, infrequently, metabolic acidosis can occur. Respiratory acidosis can occur secondary to carbon dioxide retention from respiratory depression due to ethanol intoxication. Hypoglycemia occurs during acute ethanol intoxication due to impaired gluconeogenesis resulting from changes in the NADH/NAD+ ratio associated with ethanol metabolism. Alcohol affects the CNS primarily through the γ-aminobutyric acid (GABA) and glutamate neurotransmitter systems. ETIOLOGY Alcohol is produced from fermentation/distillation of sugar from grapes (wine), grains/corn (beer/whiskey), potatoes (vodka), or sugar cane (rum) and then mixed into solution to make specific beverages. – Products are marketed according to alcohol content or proof (twice the percent). – Alcohol content ranges from 3–6% (6 to 12 proof) in beer to 40–75% (80 to 150 proof) in vodka/rum/whiskey. Alcohol is often consumed concurrently with other substances (licit and illicit), presenting a mixed clinical picture of intoxication. COMMONLY ASSOCIATED CONDITIONS Alcohol is involved in 30% of all drug overdoses. A significant percentage of adolescent trauma patients, especially victims of gunshot wounds, have positive toxicology screens for alcohol and other drugs. Ethanol use increases trauma risk by 3- to 7fold. A blood alcohol concentration (BAC) of 50 mg/dL doubles the risk of involvement in a motor vehicle crash. Among college students, alcohol use is highly associated with intimate partner violence and sexual assault.

DIAGNOSIS HISTORY Medical: Baseline health will affect patient’s response to alcohol; diabetics, for example, may have worse hypoglycemia. Type and dose of other drugs ingested: – Clinical effects and treatment for other ingestions can vary depending on substance. – Polysubstance ingestion is very common. Psychiatric history: Evaluate for possible suicidal ideation. Gathering details regarding the alcohol consumed (type, amount, and over what time period) may help predict clinical course. For example, BAC may continue rising if ingestion occurred recently. Intoxication presents clinically with signs ranging from lack of coordination, slurred speech, and confusion (BAC of 20 to 200 mg/dL) to ataxia and nausea/vomiting (BAC 200 to 300 mg/dL) to amnesia, seizures, or coma (BAC >300 mg/dL). PHYSICAL EXAM Bruises, lacerations, and fractures may suggest trauma and raise concern about CNS injury. Neurologic exam, including mental status, will assess degree of intoxication and consciousness, including patient’s ability to protect his or her airway, and risk for aspiration. Tachycardia and hypotension may indicate dehydration. Fever may suggest infection. Mental status – Average time for normalization of mental status in intoxicated adults is 3 to 3.5 hours. – Patients without clinical improvement in 3 hours should be evaluated for other causes of altered mental status. DIFFERENTIAL DIAGNOSIS Environmental – Other ingestions (overdose of sedatives or illicit drugs, such as benzodiazepines, marijuana, narcotics, lysergic acid diethylamide [LSD], and phencyclidine [PCP]) – Toxic exposures (ethylene glycol, methanol, carbon monoxide) – Head trauma Infection – Meningitis – Encephalitis – Sepsis Tumor: brain tumor Metabolic – Hypoglycemia – Ketoacidosis – Hyperammonemia – Electrolyte imbalances (hyponatremia, hypernatremia)

Miscellaneous – Increased intracranial pressure from hydrocephalus, mass, other – Stroke DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) BAC – Generally correlates with clinical picture – In children, signs of intoxication may be present at levels of 50 mg/dL. – Serum levels of 600 to 800 mg/dL can be fatal. Blood and/or urine toxicology screen – Most urine toxicology screens do not test for alcohol. – Concurrent ingestions are common. Acetaminophen level – Usually not part of the general serum toxicology screen – Consider if polysubstance ingestion suspected and/or if patient has suicidal ideation. Serum electrolytes – Alcohol is a diuretic. The associated nausea and vomiting seen with intoxication may result in severe dehydration. – Ketosis and, infrequently, metabolic acidosis can occur. Serum glucose level: Ethanol inhibits gluconeogenesis and can be associated with hypoglycemia. Blood gas can show both respiratory and metabolic acidosis.

TREATMENT GENERAL MEASURES Assess airway, breathing, and circulation (ABC). Protect airway: The patient may require intubation and mechanical ventilation. Mainstay is supportive therapy as no specific ethanol antidote exists. Appropriate trauma management as needed Because alcohol is absorbed rapidly, gastric lavage is indicated only if the patient is seen immediately after ingestion (within minutes). MEDICATION IV dextrose as needed for hypoglycemia ISSUES FOR REFERRAL Refer to substance abuse specialist (addiction medicine, psychiatrist, or certified addictions counselor) for detailed evaluation and treatment. Refer for psychiatric evaluation if depression, anxiety, suicidal ideation, or any other mental health condition is suspected. Assess for other risk-taking behaviors—including other substance use, sexual activity, use of motor

vehicles while intoxicated, weapon carrying, and delinquency—and their sequelae, including pregnancy, sexually transmitted infections, and violence. ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS Keep patient awake; watch for vomiting as patients are at risk for choking owing to depressed gag reflex. Admission criteria – Unstable vital signs (hypotension) – Persistent CNS depression/impaired mental status – Potential severity of comorbid psychiatric conditions (depression/suicidality) – Inability to contact a parent/guardian IV fluids for dehydration and hypotension Observe and monitor vital signs and neurologic status. Discharge criteria – Stable vital signs – Patient awake, alert, responsive, and oriented – Decreasing BAC – Parent/guardian fully informed about patient’s alcohol use DIET NPO secondary to depressed gag reflex PROGNOSIS BAC serum levels of 600 to 800 mg/dL can be fatal. COMPLICATIONS Diuresis and dehydration Vasodilation, hypotension, and tachycardia Vomiting, aspiration, potential respiratory arrest Hypoglycemia Metabolic acidosis Impaired mental status Engagement in risk-taking behaviors (e.g., other drug use, unprotected intercourse) while intoxicated CNS depression Gastritis GI bleeding Acute pancreatitis Motor vehicle collisions associated with driving while intoxicated Alcoholism Alcohol withdrawal following a period of intoxication in chronic users (symptoms include tachycardia, elevated blood pressure, irritability, nausea, vomiting, and tremor)

ADDITIONAL READING

Centers for Disease Control and Prevention. 2011 Youth Risk Behavior Survey. http://www.cdc.gov/yrbs. Accessed September 1, 2013. Howland J, Rohsenow DJ. Risks of energy drinks mixed with alcohol. JAMA. 2013;309(3):245–246. Johnston LD, O’Malley PM, Bachman JG, et al. Monitoring the Future National Results on Drug Use: 2012 Overview, Key Findings on Adolescent Drug Use. Ann Arbor, MI: Institute for Social Research, The University of Michigan; 2013. Merrill JE, Carey KB. Drinking over the lifespan: focus on college ages. Alcohol Res. 2016;38(1):103– 114. Rayar P, Ratnapalan S. Pediatric ingestions of house hold products containing ethanol: a review. Clin Pediatr (Phila). 2013;52(3):203–209. The Center on Alcohol Marketing and Youth. Prevalence of underage drinking. http://www.camy.org/factsheets/sheets/Prevalence_of_Underage_Drinking.html. Accessed March 15, 2018.

CODES ICD10 F10.920 Alcohol use, unspecified with intoxication, uncomplicated F10.929 Alcohol use, unspecified with intoxication, unspecified T51.0X4A Toxic effect of ethanol, undetermined, initial encounter

FAQ Q: How quickly is alcohol metabolized? A: The liver metabolizes approximately 10 g of ethanol per hour, which corresponds to a decline in BAC of 18 to 20 mg/dL/h; clearance rates are related to prior exposure to alcohol, ranging from 15 to 20 mg/dL in inexperienced drinkers to 25 to 35 mg/dL in patients with chronic alcohol abuse. Q: What is binge drinking in youth? A: For children 9 to 13 years old and girls 14 to 17 years old, 3 or more drinks; for boys 14 to 15 years old, 4 or more drinks Q: Are younger children at any increased risk from alcohol poisoning? A: Ethanol inhibits gluconeogenesis; younger children have an increased risk of hypoglycemia because they have relatively smaller hepatic glycogen stores; however, children tend to have more rapid clearance rates (up to 30 mg/dL/h). Q: How is alcohol smoked? A: Alcohol can be vaporized and inhaled using dry ice or by using purchased or homemade vaporizers. The inhaled vapor bypasses the stomach and liver and thus reaches the brain much faster. Vaporizing or smoking alcohol has a higher risk for alcohol poisoning.

ALLERGIC CHILD Barry J. Pelz, MD Anne Marie Singh, MD

BASICS Allergic diseases include atopic dermatitis, food allergy, asthma, and allergic rhinitis. Atopic or allergic diseases are becoming more and more prevalent in the population. Food allergy in its most severe form may manifest as anaphylaxis. These conditions may present in a variety of ways as described below. DESCRIPTION Atopic dermatitis – Atopic dermatitis (or eczema) is characterized by chronic, relapsing, pruritic inflamed skin, which is often erythematous, xerotic, and/or excoriated. – Atopic dermatitis may occur in isolation without other atopic diseases or it may be the beginning of the “atopic march” preceding the onset of other atopic conditions, which may include food allergy, asthma, and/or allergic rhinitis. Urticaria – Refers to hives or the erythematous wheals that occur when histamine is released from mast cells – May be caused by a number of triggers – Viral infection is the most common cause of urticaria in children. – The allergic child may develop urticaria when an antigen such as a food causes IgE-mediated release of mast cell mediators. Food allergy – Presents with an IgE-mediated reaction after exposure to a food to which the child is sensitized – Reactions may involve any number of allergic symptoms, including urticaria, lip or tongue swelling, closing of the throat, wheezing, shortness of breath, hypotension, lethargy, repeated vomiting after allergen ingestion, diarrhea, or any combination of the above. – The most common food allergens include cow’s milk, egg, peanut, tree nuts, wheat, soy, fish, and shellfish. – Food allergy should be distinguished from food intolerance, which does not have an IgE basis and does not carry a risk of anaphylaxis. Asthma – An obstructive airway disease characterized by recurrent wheezing, bronchoconstriction, increased mucous production, and airway inflammation – Asthma is one of many potential causes of wheezing in children. – Wheezing with RSV and human rhinovirus infection are associated with the development of asthma. Allergic rhinitis and conjunctivitis – A condition in which children are sensitized to perennial allergens, seasonal allergens, or both – Perennial allergens include dust mite, cockroach, animal dander, and some molds. – Seasonal allergens include tree pollens, grass pollens, weed pollen, ragweed pollen, and other

molds. – Symptoms may include watery eyes, itchy eyes, rhinorrhea, nasal discharge, itchy nose, sneezing, postnasal drip, throat clearing, headache, sinus pressure, nasal obstruction, mouth breathing, or snoring. – Symptoms may be seasonal, year-round, or triggered by exposure to specific allergens (such as cats or dogs). RISK FACTORS Genetics Children who do not have a family history of atopy have approximately a 25% chance of being atopic. For children with at least one parent who is atopic, the risk of atopy approximately doubles compared to the general population. PATHOPHYSIOLOGY Most of these allergic conditions are IgE mediated, and all result from a complex interaction between multiple genetic and environmental factors.

DIAGNOSIS A thorough history and physical examination are the keys to diagnosing the allergic child. Confirmatory tests should be used when indicated. HISTORY History should elicit signs and symptoms of allergic diseases while at the same time exploring other potential etiologies for the child’s symptoms. The allergic child should have symptoms of atopic dermatitis, urticaria, wheezing, reactions to foods, or symptoms of allergic rhinitis and conjunctivitis such as sneezing, itchy eyes, watery eyes, itchy nose, runny nose, or itchy throat. The practitioner should also review the family history because atopic disease often runs in families. PHYSICAL EXAM A complete physical exam is essential to rule out systemic diseases that can mimic allergic disease. Ocular signs may include the following: – Dark circles under the eyes or the “allergic shiners” which result from venous stasis secondary to passive congestion in the nose, impeding venous return from the vessels under the eyes – Cobblestoning of the conjunctiva – Erythematous injection of the conjunctiva – Dennie-Morgan lines or infraorbital folds associated with suborbital edema secondary to chronic inflammation from atopic dermatitis – Clear stringy ocular discharge Nasal allergic signs may include the following: – Pale edematous nasal mucosa – Clear nasal discharge with or without occlusion

– Nasal crease across the bridge of nose secondary to repeated upward rubbing of the nose from “the allergic salute” – Nasal polyps may be present, although they are much more common in adults and should prompt consideration of diseases such as cystic fibrosis when seen in children. Ear allergic signs may include the following: – Fluid in the middle ear or retracted tympanic membranes – Eustachian tube dysfunction associated with allergic inflammation Throat allergic signs may include the following: – Cobblestoning of the posterior pharynx secondary to submucosal lymphoid hyperplasia Lung allergic signs may include the following: – Wheezes, rhonchi, decreased air entry, prolonged expiration, and chronic obstruction secondary to allergic responses Skin allergic signs may include the following: – Eczema, hives, angioedema, and/or dermatographism DIFFERENTIAL DIAGNOSIS The differential for allergic diseases is extensive and should focus on considering other etiologies for the symptoms. Ear/nose symptoms – Eye findings may be caused by physical or chemical irritants or by viral or bacterial infection. – Allergic rhinitis symptoms may resemble upper respiratory infections, sinusitis, nasal foreign bodies, or nonallergic rhinitis. – A number of medications can lead to rhinitis medicamentosa or symptoms of nasal congestion due to medication use. – Systemic diseases such as cystic fibrosis, immotile cilia syndrome, Kartagener syndrome, or immunodeficiencies may present with recurrent nasal or lung symptoms, or sinopulmonary infections. – Lung symptoms may be caused by physical or chemical irritants including tobacco smoke, environmental pollution, and inhalants. Chest symptoms – Lung symptoms may also result from gastroesophageal reflux leading to cough (often nocturnal) or cough with recumbency. – Foreign body aspiration may produce lung symptoms and auscultatory signs, although typically, foreign bodies create more focal lung findings. – Anatomic defects in the airway may also result in symptoms that are similar to allergic symptoms. Skin symptoms – Skin findings may be caused by a number of etiologies including irritant dermatitis; viral exanthems; autoimmune disorders; bacterial, fungal, or parasitic infections. Multisystem findings – Anaphylaxis may sometimes be confused with angioedema, vocal cord dysfunction, globus sensation, or with other causes of shock (sepsis, hypovolemia, cardiogenic). – Food allergy may sometimes be confused with food intolerance, but food intolerances typically present with abdominal discomfort, bloating, flatulence, or nonspecific malaise, whereas food

allergy presents with true IgE-mediated reactions. DIAGNOSTIC TESTS & INTERPRETATION The diagnosis of allergic diseases can be strongly suggested based on history and physical alone. Specific tests can be done by a specialist in allergy and immunology in order to be properly interpreted. Often, initial therapy can be initiated without definitive tests. Once the allergic child is referred to the allergist, testing may include the following: Immediate hypersensitivity testing – Skin prick tests (percutaneous testing) to suspected allergens based on history may demonstrate IgE sensitization if positive. – Intradermal skin tests for patients who have a negative skin prick test and a suspicious history pose a greater risk of systemic reactions but can be done for environmental allergens, not for foods. Blood-specific IgE testing – ImmunoCAP® tests measure free serum IgE to a specific antigen to which a particular patient may be sensitized. – Although panels are available, these tests are best done for targeted potential allergens that are suggested by the history. These should be interpreted by an allergist with experience in interpreting and guiding therapy. – Incorrect use or interpretation of ImmunoCAP® testing may result in inappropriate dietary restrictions, nutritional deficits, and undue anxiety. – ImmunoCAP® levels may be trended over time to help monitor for the development of tolerance. Eosinophilia – Eosinophils in peripheral blood, respiratory secretions, or nasal samples may be indicative of an allergic diathesis. Pulmonary function tests (PFTs) – PFTs or spirometry should be obtained on asthmatic children or in children with respiratory allergic histories to evaluate for obstructive diseases.

TREATMENT GENERAL MEASURES The main principle of therapy for allergic diseases is avoidance of allergic triggers. For atopic dermatitis, general treatment methods include measures to help lock moisture into skin, treat inflammation when present, control pruritus, minimize skin irritants, and treat infection when present. For food allergy, the most important therapeutic measure is strict avoidance of the food that causes the allergy in order to prevent an allergic reaction. – Children at risk for a reaction to a food allergen should be prescribed an epinephrine autoinjector to use in the event of systemic symptoms or anaphylaxis. – An emergency action plan should be provided, reviewing the signs and symptoms of a reaction and the doses and medications that should be used in the event that an accidental ingestion occurs. – Infants with food allergy or moderate to severe atopic dermatitis should be evaluated by an allergist

who will screen for the possible early introduction of peanut to prevent development of peanut allergy. For allergic rhinitis, systemic antihistamines may be helpful in controlling symptoms. Many patients also benefit from intranasal corticosteroids when indicated. – Specific environmental control measures may be indicated based on specific skin testing results. – Pets should be kept out of the bedroom if a child has allergic stigmata due to animal dander. – To minimize exposure to dust mite allergen, bedding should be placed in dust mite encasements and washed in hot water at least once every 2 weeks. – Immunotherapy may be indicated for patients with allergic rhinitis or venom allergy. For patients with asthma, treatment should follow the latest National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) asthma guidelines with consideration to the child’s symptomatology, impairment, and risk. Therapies may include use of rescue inhalers, controller medications such as inhaled corticosteroids, leukotriene antagonists, and others (see Appendix). Control of comorbidities such as allergic rhinitis and gastroesophageal reflux disorder (GERD) are also important therapeutic steps. ISSUES FOR REFERRAL Any child with allergic symptoms may benefit from referral to an allergist-immunologist. A patient failing medical management of upper respiratory or ocular allergies with routine antihistamine/decongestant medications may be referred to an allergist who can help identify triggers contributing to the problem. Poorly controlled asthma not responding to intermittent inhaled β-agonists or an asthmatic child who is symptomatic between exacerbations or has an atypical pattern of exacerbations should be referred. Asthma patients with frequent hospitalizations or steroid courses should be referred. Patients who are absent from school frequently because of allergic or asthmatic symptoms should be referred. Patients with food allergy, drug allergy, latex allergy, or difficult-to-manage atopic dermatitis should also be referred to an allergist. Infants with moderate to severe atopic dermatitis or other food allergy should be referred to an allergist.

ONGOING CARE PROGNOSIS In general, environmental allergies that cause rhinitis and asthma persist into adulthood. About 50% of milk-allergic children may outgrow their allergy by school age and about 80% by age 16 years. Those who tolerate baked milk have a higher likelihood of outgrowing the allergy. About 70% of egg-allergic children may outgrow their egg allergy by age 16 years. Children who tolerate baked egg seem more likely to outgrow the allergy. Children may occasionally outgrow peanut (~20% obtain natural tolerance), tree nut (~10%), or shellfish allergy. Allergic diseases may have a significant impact on the patient and family’s quality of life and may lead

to issues with anxiety and mental health. Early introduction of peanut in high-risk children significantly lowers the risk of peanut allergy.

ADDITIONAL READING Adkinson NF, Bochner BS, Busse WW, et al. Middleton’s Allergy Principles and Practice. 7th ed. Philadelphia, PA: Mosby; 2009. Du Toit G, Roberts G, Sayre PH, et al; for LEAP Study Team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803–813. Hatzler L, Hofmaier S, Papadopoulos NG. Allergic airway diseases in childhood—marching from epidemiology to novel concepts of prevention. Pediatr Allergy Immunol. 2012;23(7):616–622. Langley EW, Gigante J. Anaphylaxis, urticaria, and angioedema. Pediatr Rev. 2013;34(6):247–257. Papadopoulos NG, Arakawa H, Carlsen KH, et al. International consensus on (ICON) pediatric asthma. Allergy. 2012;67(8):976–997. Wood RA, Sicherer SH, Vickery BP, et al. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol. 2013;131(3):805–812.

CODES ICD10 L20.9 Atopic dermatitis, unspecified L27.2 Dermatitis due to ingested food J45.909 Unspecified asthma, uncomplicated

FAQ Q: Do children outgrow allergies? A: In general, environmental allergies that cause rhinitis and asthma persist into adulthood. However, most children outgrow food allergies to milk, egg, soy, and wheat. Children may occasionally outgrow peanut, tree nut, or shellfish allergies. Q: If a parent is allergic to a specific allergen, can the child inherit this allergy? A: Children inherit the tendency to be allergic, but they do not inherit specific allergies. Q: How can allergies be prevented? A: In general, allergy prevention is currently not possible, but research in this field is ongoing. Early introduction of peanut in the 1st year of life may prevent the development of peanut allergy in high-risk infants.

ALOPECIA (HAIR LOSS) Hope E. Rhodes, MD, MPH, FAAP Terry Kind, MD, MPH

BASICS DESCRIPTION Absence of hair where it normally grows Categorized as acquired or congenital – Most cases are acquired: Tinea capitis is most common, followed by traumatic alopecia and alopecia areata. Also categorized as diffuse or localized – Most cases of alopecia are localized and, of these, tinea capitis is the most common. Many normal healthy newborns lose their hair in the first few months of life. – Hair loss may be exacerbated by friction from bedding/sleep surface, especially in atopic infants. Normally, about 50 to 100 hairs are shed and simultaneously replaced every day. 90% of alopecia cases are due to the following disorders: – Tinea capitis – Alopecia areata – Traction alopecia – Telogen effluvium Alopecia is preceded by a psychologically or physically stressful event 6 to 16 weeks prior to the onset of hair loss. Growing hairs convert rapidly to resting hairs. RISK FACTORS Genetics Alopecia areata – Polygenic with variety of triggering factors – Family history in 10–42% of cases – Males and females equally affected – Onset usually before age 30 years Monilethrix (also called beaded hair) – A rare autosomal dominant disorder COMMONLY ASSOCIATED CONDITIONS Trichotillomania is frequently associated with a finger-sucking habit.

DIAGNOSIS HISTORY Attempt to classify the alopecia. This will guide the diagnosis and treatment plan.

Question: Is the loss acquired or congenital? Is the alopecia treatable? Is it likely to be self-limited? Significance: Consider most likely diagnoses, including tinea capitis, traumatic alopecia, and alopecia areata. Question: Associated abnormalities? Significance: may be part of a syndrome Question: Is there an endocrine abnormality or a toxin/medication effect? Significance: Some of these would require prompt attention. Question: Assess extent of hair loss. Significance: – Increased amount of hair in the brush or in the shower/tub drain? – Does hair appear or feel thinner? – Patches of hair loss or broken hairs noted? Question: Considering trichotillomania? Significance: Note that patients often deny hair-pulling. Direct confrontation is rarely helpful. PHYSICAL EXAM Assess localized versus diffuse hair loss. Finding: appearance of the scalp Significance: – Alopecia areata: Except for well-demarcated hair loss, scalp appears normal with smooth surface. – Tinea capitis: Scalp is often scaly and may be erythematous; areas of hair loss with broken hair stubs, referred to as black-dot alopecia Finding: bizarre configuration and irregular border; hairs of varying lengths Significance: distinguishes traction/traumatic alopecia from alopecia areata Finding: short broken hairs but not black dots Significance: Short hairs are usually associated with trichotillomania, whereas black-dot alopecia is seen with tinea capitis. Finding: frontal, vertex, or bitemporal decreased hair density in adolescents Significance: may be adolescent-onset, androgenetic alopecia Finding: Hair shaft varies in thickness, with small node-like deformities (like beads), increased breakage, and partial alopecia. Significance: – Monilethrix – Other hair-shaft abnormalities with increased fragility include pseudomonilethrix, trichorrhexis, pili torti, pili bifurcati, Menkes kinky hair syndrome, and trichothiodystrophy. Finding: cervical or occipital lymphadenopathy Significance: – Often associated with infectious etiology (e.g., tinea capitis) Finding: associated systemic signs or any nonscalp findings Significance: may signify a genetic syndrome or endocrine abnormality Finding: nail defects such as dystrophic changes and fine stippling Significance:

– Nail defects are seen in 10–20% of cases of alopecia areata. – Nail defects accompanying localized alopecia along with syndactyly, strabismus, and dermal hypoplasia may be found in Goltz syndrome. – In ectodermal dysplasias, nails, hair, teeth, or glands may be affected. Finding: pubic hair and eyebrow hair loss Significance: – Found in a form of alopecia areata called alopecia universalis, where nearly all body hair is lost (alopecia totalis involves the loss of all scalp hair) – Body hair loss such as pubic hair or eyebrow hair may also occur in trichotillomania. DIFFERENTIAL DIAGNOSIS Consider the most likely diagnoses first. Infectious – Tinea capitis – Varicella – Syphilis Congenital – Aplasia cutis congenita – Incontinentia pigmenti – Oculomandibulofacial syndrome (sparse hair, hypoplastic teeth, cataracts, short stature) – Goltz syndrome (alopecia, focal dermal hypoplasia, strabismus, nail dystrophy) – Triangular alopecia of the frontal scalp – Focal dermal hypoplasia – Hair-shaft defects (trichodystrophies) – Ectodermal dysplasias – Nevi – Progeria Nutritional – Zinc deficiency – Marasmus – Kwashiorkor – Anorexia or bulimia – Hypervitaminosis A – Celiac disease Endocrinologic – Androgenetic alopecia – Hypothyroidism – Hyperthyroidism – Hypoparathyroidism – Hypopituitarism – Diabetes mellitus Autoimmune

– Alopecia areata – Systemic lupus erythematosus – Scleroderma Trauma – Traction alopecia – Trichotillomania – Scalp electrode scar from in utero monitoring Toxic exposures – Antimetabolites – Anticoagulants – Antithyroid medications – Heavy metals (e.g., arsenic, lead) – Radiation Stress – Trichotillomania Miscellaneous: – Telogen effluvium – Darier disease (keratotic crusted papules, keratosis follicularis) – Lichen planus – Burn – Stress DIAGNOSTIC TESTS & INTERPRETATION Test: fungal culture Significance: – Recommended when assessing for tinea capitis as a cause of alopecia – Definitive results may take up to several weeks; may treat while awaiting results – Using a cotton-tipped applicator, culturette, toothbrush, or direct plating on Sabouraud dextrose agar, culture will be positive for Trichophyton tonsurans in >90% of cases in North America. This species is often involved in human to human transmission. – Less common are Microsporum canis, Microsporum audouinii, Trichophyton mentagrophytes, and Trichophyton schoenleinii. Test: dermatophyte test medium (DTM) Significance: – Assessing for tinea capitis – Definitive results may take from days to weeks. If dermatophyte colonies grow on the medium, the phenol red indicator in the agar will turn from yellow to red. Test: Wood light (lamp) examination Significance: – M. canis, M. audouinii, or T. schoenleinii fluoresces green. – T. tonsurans does not fluoresce. Test: potassium hydroxide (KOH) exam

Significance: – The KOH exam is another way to assess for tinea capitis. – Hyphae and spores within hair shaft indicate tinea capitis. – With Microsporum, spores surround the hair shaft. Test: endocrine testing Significance: – Alopecia areata or diffuse alopecia is associated with several endocrine disorders (e.g., hyperthyroidism, diabetes). – Based on history of physical exam, consider relevant screening tests or referral to an endocrinologist or dermatologist for further evaluation. – Routine screening for autoimmune disorders is generally not indicated. Test: hair-pluck test Significance: – Used to determine the ratio of telogen (resting) to anagen (growing) hairs – ~50 hairs are plucked (with one firm tug using a hemostat clamped around the hair ~1 cm from the scalp) and examined under the low-power lens of a microscope to determine the percentage of hairs that are telogen and anagen hairs. – >25% telogen hairs are indicative of telogen effluvium. Test: scalp biopsy Significance: – Can help to distinguish alopecia areata and trichotillomania – In alopecia areata, hair follicles become small but continue to produce fine hairs; there is mitotic activity in the matrix and often inflammation is present. – In trichotillomania, follicles are not small. They are usually in a transitional (catagen) phase and no longer produce normal hair shafts. Keratinous debris, fibrosis, and clumps of dark melanin pigment are present. Significant inflammation is absent. – In telogen effluvium, follicles remain intact without inflammation.

TREATMENT GENERAL MEASURES Treatment of alopecia is guided by the underlying cause. Most patients with alopecia areata do not need treatment, as regrowth will occur spontaneously. Other than reassurance and waiting, there is no proven effective long-term therapy. Topical steroids may show short-term benefit. There are no randomized clinical trials on the use of topical immunotherapy or intralesional steroids. Systemic treatment is needed for tinea capitis; topical antifungals alone are not adequate. Topicals are recommended to decrease fungal shedding and risk of spread to others. Infectious causes of alopecia (such as with tinea capitis) should be treated promptly. If alopecia signifies a toxic exposure or an endocrine abnormality, the underlying condition may require prompt diagnosis and treatment.

Caution regarding side effects of all potential treatments. MEDICATION First Line For tinea capitis: microsize griseofulvin 20 to 25 mg/kg/24 h (maximum 1 g) or ultramicrosize griseofulvin 10 to 15 mg/kg/24 h (maximum 750 mg) orally once per day for 4 to 6 weeks; approved for children >2 years of age Most alopecia areata does not require treatment. Second Line For tinea capitis: Terbinafine may be equally as effective in treating tinea caused by T. tonsurans but is still considered 2nd-line therapy. Itraconazole or fluconazole may be effective. Only terbinafine is FDA-approved for this condition. For alopecia areata: There is limited evidence for long-term effectiveness of any treatment. For trial of other therapies (intralesional steroid, topical immunotherapy), seek consultation with a dermatologist. COMPLEMENTARY & ALTERNATIVE THERAPIES Hypnotherapy, massage, acupuncture, and onion juice are among the complementary therapies that have been tried for conditions like alopecia areata and trichotillomania. Of note, although many patients try CAM for alopecia, more research is needed.

ONGOING CARE PROGNOSIS Tinea capitis, alopecia areata, and traction alopecia – Hair will regrow, may take months – There is a poorer prognosis with alopecia universalis. 100 variant alleles identified. The classic PiZZ genotype is the result of a point mutation at position 342 in the AAT gene, which encodes a substitution of lysine for glutamate. The S allele (second most common mutation) occurs from a substitution of valine for glutamate at

position 246. Patients with PiZZ alleles have serum AAT levels, which are 1:64) Donath–Landsteiner test should be performed in cases of suspected paroxysmal cold hemoglobinuria. ALERT A negative Coombs test can occur when small numbers of IgG or C3 molecules are present on the red cell membrane or if most of the coated red blood cells are cleared from circulation (i.e., in cases of less severe hemolysis, low-affinity antibodies, or in cases of very severe, rapid clearance). Radiolabeled Coombs test or enzyme immunoassays are more sensitive diagnostic tests in these circumstances. Reticulocytopenia may occur in some cases where the antibody coats and removes reticulocytes.

TREATMENT MEDICATION First Line Corticosteroids – Indication: In IgG-mediated disease, steroids have been shown to interfere with macrophage Fc and C3b receptors responsible for RBC destruction. In addition, they have been shown to elute IgG Ab from the RBC surface (improving survival); induces remission in 80–85% of cases. In chronic, warm, AIHA, pulsed high-dose dexamethasone has been shown to be effective in some cases. – Complications: Both short- and long-term side effects Generally not effective in cold agglutinin disease – Dose: Start prednisone PO/methylprednisolone IV at 2 mg/kg/24 h in divided doses. Tapering of steroids should begin after a therapeutic response is achieved (may take several days to weeks). – Goal: Initially, to return to normal hemoglobin level with tolerable doses of steroid or off steroids entirely In some patients, goal may be achieving decreased hemolysis and a clinically asymptomatic state with minimal steroid side effects. Alternative treatments should be considered for patients unresponsive to steroids or who require high doses for maintenance of hemoglobin level. Second Line IV immunoglobulin – Indication: May be useful in selected cases of immune hemolytic anemia unresponsive to steroids – Mechanism of action is not entirely clear.

– Effect is usually temporary; retreatment may be required every 3 to 4 weeks. – Complications: Aseptic meningitis Theoretical risk of transfusion-transmitted viral infection Large doses of IVIG have been associated with hemolytic anemia. – Expensive – Dose: Up to 1 g/kg/24 h for 5 days has been required to achieve a beneficial effect. Plasmapheresis/exchange transfusion – Indication: Will slow the rate of hemolysis in severe disease, especially if IgM-mediated – Indicated if thrombotic thrombocytopenic purpura cannot be excluded – Complications: Only of short-term benefit – Expensive Rituximab: Monoclonal anti-CD20 antibody likely works through depletion of B cells. – Indicated in refractory AIHA (375 mg/m2 weekly for 2 to 4 weeks) – Response 40–100% – Particularly useful in warm AIHA – Adverse effects: infusion associated: fever, chills, rigors, hypertension, bronchospasm; Late onset: rare risk of viral infections, hypogammaglobulinemia Immunosuppressive agents (antimetabolites and alkylating agents) – Indication: When there is a clinically unacceptable degree of hemolysis that is refractory to 1st-line agents May be used in conjunction with steroids Some have been effective in cold agglutinin disease. – Complications: There are varying side effects dependent on the agent used. Therefore, clinical indications must be strong and exposure to drug should be limited. – Dose: Adjusted to maintain WBC >2,000, absolute neutrophil count (ANC) >1,000, and platelet count at 50,000 to 100,000 cells/mm3 Alemtuzumab (anti-CD52): may be effective very refractory AIHA particularly secondary to B-cell chronic lymphocytic leukemia (B-CLL) ADDITIONAL THERAPIES Blood transfusion: Should only be used with great caution in this setting in patients with very low hemoglobin/brisk hemolysis because of difficulty with appropriate cross-matching Indication: physiologic compromise from the anemia (usually only in severe acute onset) Considerations: – The blood bank may be unable to find compatible blood. In IgG-mediated disease, autoantibody is usually pan-reactive; therefore, you must use the least incompatible unit of blood.

– In cold agglutinin disease, use a blood warmer for all infusions to decrease IgM binding, and monitor for acute hemolysis during transfusion. SURGERY/OTHER PROCEDURES Splenectomy Indication: Patients unresponsive to medical management, who require moderate- to high-maintenance doses of steroids or who develop steroid intolerance may be candidates. Not effective in cold agglutinin disease Response rate is 50–70%, with many partial remissions.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patient Monitoring Hemoglobin level q4h–q12h (depending on severity) until stable Reticulocyte count: daily Spleen size: daily Hemoglobinuria: daily Coombs: weekly PROGNOSIS Dependent on age, underlying disorder (if any), and response to therapy. See also “Description” section (natural history). Mortality in pediatric series ranged from 9% to 19%. COMPLICATIONS May be increased risk of venous thrombosis in patients with AIHA May be associated with a predisposition to lymphoproliferative disorders Gallstones related to chronic hemolysis

ADDITIONAL READING Barros MMO, Blajchman MA, Bordin JO. Warm autoimmune hemolytic anemia: recent progress in understanding the immunobiology and treatment. Transfus Med Rev. 2010;24(3):195–210. Hoffman PC. Immune hemolytic anemia—selected topics. Hematology Am Soc Hematol Educ Program. 2009:80–86. Miano M. How I manage Evans syndrome and AIHA cases in children. Br J Haematol. 2016;172(4):524–534. Petz LD. Cold antibody autoimmune hemolytic anemias. Blood Rev. 2008;22(1):1–15. Teachey DT, Lambert MP. Diagnosis and management of autoimmune cytopenias in childhood. Pediatr Clin North Am. 2013;60(6):1489–1511. Vagace JM, Bajo R, Gervasini G. Diagnostic and therapeutic challenges of primary autoimmune haemolytic anaemia in children. Arch Dis Child. 2014;99(7):668–673.

CODES ICD10 D59.1 Other autoimmune hemolytic anemias D59.0 Drug-induced autoimmune hemolytic anemia

FAQ Q: Will the anemia go away? A: Children with cold autoantibodies tend to have short-lived illness, whereas children with warm antibodies often have a chronic clinical course characterized by periods of remissions and relapses. Q: Is this contagious? A: No. Another child may acquire the same viral illness; however, the body’s response to produce an autoantibody is dependent on the individual patient.

AVASCULAR (ASEPTIC) NECROSIS OF THE FEMORAL HEAD (HIP) Craig Munns, FRACP, MBBS, PhD

BASICS DESCRIPTION Avascular (aseptic) necrosis results from the interruption of the blood supply to bone (either traumatic or nontraumatic occlusion). The femoral head is the most common site. A self-limiting idiopathic avascular necrosis of the hip that occurs in children is known as Perthes disease (see “Perthes Disease” chapter). RISK FACTORS Genetics Variable, depending on cause Steroid-induced avascular necrosis may have an underlying genetic predisposition. PATHOPHYSIOLOGY Death and necrosis of bone with gradual return of blood supply Necrotic bone gradually resorbed and replaced by new bone During bone resorption, structural integrity of femoral head may be reduced, leading to collapse. ETIOLOGY Traumatic – Slipped capital femoral epiphysis – Hip fracture – Hip dislocation – Complication of casting, bracing, surgery Nontraumatic – Steroids or chemotherapy – Malignancy (leukemia) – Idiopathic (older, after physeal closure); similar to adult avascular necrosis – Idiopathic (younger, before physeal closure, Perthes disease) – Caisson disease – Sickle cell disease – Septic arthritis – Gaucher disease – Viral infection (HIV, CMV) – Radiation therapy – Hypercoagulable states

DIAGNOSIS HISTORY Onset (gradual or after traumatic event) Association with the following: – Trauma – Medications (steroids or chemotherapy) – Casting, splinting, surgery (iatrogenic) – Pain, limping – Stiffness (decreased range of motion) – Perthes disease may occasionally be bilateral or occur in contralateral hip at a later time point. PHYSICAL EXAM Gait – Limping – Antalgic (“against pain”) gait (shortened stance phase relative to swing phase) – Trendelenburg gait (tilting of pelvis during the stance phase of gait; pelvis rises on the side not taking weight) Test and note range of motion: – Flexion and extension – Abduction and adduction – Internal and external rotation Hip joint irritability (short arc rotation) Signs of other disease processes associated with avascular necrosis (e.g., sickle cell disease) Physical examination pearl – Loss of internal rotation usually first and most affected loss of motion DIFFERENTIAL DIAGNOSIS Trauma – Osteochondral fracture – Impaction fracture – Epiphyseal/physeal fracture Infection – Osteomyelitis – Septic arthritis Neoplastic process: epiphyseal tumors (chondroblastoma, Trevor disease, etc.) Rheumatologic processes Skeletal dysplasia, particular if bilateral hip involvement DIAGNOSTIC TESTS & INTERPRETATION Laboratory examinations should be normal in most forms of avascular necrosis of the femoral head. Exceptions: – Sickle cell disease

– Septic arthritis – Chemotherapy Radiographic findings: – Sclerosis – Subchondral fracture – Collapse – Reossification – Repair Magnetic resonance imaging (MRI) – Bone edema – If contrast medium used, area of reduce blood flow evident Bone scan – Reduced signal in affected hip Other potential findings: – Cysts – Physeal growth arrest (young) – Early osteoarthritis – Subluxation

TREATMENT MEDICATION NSAIDs may reduce pain by decreasing associated inflammation but may also reduce new bone formation. If associated with corticosteroid use, discontinuation or elimination of steroids may be helpful. Antiresorptive therapy (bisphosphonate/receptor activator of nuclear factor-κB (RANK) ligand inhibitor) may reduce pain and preserve joint shape; research studies using this approach are ongoing. GENERAL MEASURES Maintain range of motion (physical therapy, traction, continuous passive motion). Contain the femoral head in the acetabulum (see treatment principles listed in “Perthes Disease” chapter). Duration of therapy variable, depending on cause Reduced weight bearing on affected hip may help prevent collapse. SURGERY/OTHER PROCEDURES Redirectional osteotomy Femoral or acetabular reorientation Core decompression to stimulate new blood supply

ONGOING CARE

DIET Thought not to alter disease process Recommend general balanced diet. During immobilization, excessive weight gain may occur. PROGNOSIS Depends on extent of femoral head collapse Good if mild involvement and patient is young Timing of improvement is variable, dependent on etiology. Moderate to severe cases often have significant collapse and end up requiring a total hip replacement. COMPLICATIONS Joint collapse with decreased range of motion, pain, limping Osteoarthritis Physeal arrest with growth disturbance ALERT Signs to watch for: Subluxation Early osteoarthritis Growth arrest

ADDITIONAL READING Lahdes-Vasama T, Lamminen A, Merikanto J, et al. The value of MRI in early Perthes’ disease: an MRI study with a 2-year follow-up. Pediatr Radiol. 1997;27(6):517–522. Mont MA, Cherian JJ, Sierra RJ, et al. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg Am. 2015;97(19):1604–1027. Padhye B, Dalla-Pozza L, Little DG, et al. Use of zoledronic acid for treatment of chemotherapy related osteonecrosis in children and adolescents: a retrospective analysis. Pediatr Blood Cancer. 2013;60(9):1539–1545. Roposch A, Mayr J, Linhart WE. Age at onset, extent of necrosis, and containment in Perthes disease. Results at maturity. Arch Orthop Trauma Surg. 2003;123(2–3):68–73. Sharma S, Leung WH, Deqing P, et al. Osteonecrosis in children after allogeneic hematopoietic cell transplantation: study of prevalence, risk factors and longitudinal changes using MR imaging. Bone Marrow Transplant. 2012;47(8):1067–1074. Shipman SA, Helfand M, Moyer VA, et al. Screening for developmental dysplasia of the hip: a systematic literature review for the US Preventive Services Task Force. Pediatrics. 2006;117(3):e557– e576. Tokmakova KP, Stanton RP, Mason DE. Factors influencing the development of osteonecrosis in patients treated for slipped capital femoral epiphysis. J Bone Joint Surg Am. 2003;85-A(5):798–801.

CODES

ICD10 M87.059 Idiopathic aseptic necrosis of unspecified femur M91.10 Juvenile osteochondrosis of head of femur, unspecified leg M87.052 Idiopathic aseptic necrosis of left femur

FAQ Q: What type of medication is most often associated with avascular necrosis of the hip? A: Corticosteroids Q: For avascular necrosis in children (Perthes disease of the hip, for example), is younger or older age associated with a better prognosis? A: Younger age (50 years HIV/AIDS Immunosuppressive medications Malignancy Primary immunodeficiency syndrome Genetics There is no known genetic predisposition. GENERAL PREVENTION Prevention begins with avoidance of tick bites.

Simple measures include wearing long-sleeved shirts and long pants, with pants tucked into the socks in tick-infested areas. Avoid endemic regions during the peak months of May to September. Light clothing will make ticks easier to see. Use N,N-Diethyl-meta-toluamide (DEET)-containing insect repellents during outdoor activities. Spraying one’s clothing with a permethrin tick repellent may be helpful. Children and dogs should be inspected daily for ticks after being outside. Prophylaxis is not recommended after a tick bite. No vaccine is currently available. There is currently no universal laboratory screening of blood products. PATHOPHYSIOLOGY Babesial infection of the erythrocyte causes membrane damage and lysis, which promotes adherence to the endothelium and microvascular stasis. This process results in a hemolytic anemia. The spleen plays an important role in decreasing the protozoal load through antibody production and filtering of abnormally shaped infected red blood cells. ETIOLOGY The protozoa is transmitted by a bite from the tick Ixodes scapularis (deer tick), the same vector responsible for transmission of Borrelia burgdorferi (the causative agent in Lyme disease). The white-footed mouse (Peromyscus leucopus) is the primary reservoir host of Babesia. Incubation period – Usually 1 to 4 weeks for tick-transmitted disease – 1 to 9 weeks for transfusion-associated disease Human-to-human transmission is limited to infection through contaminated blood. – Babesiosis is currently the most common transfusion-transmitted infection in the United States. – Rare cases of transplacental and perinatal infection have been reported. COMMONLY ASSOCIATED CONDITIONS Two thirds of patients have concurrent Lyme disease. – Coinfections with Borrelia account for 80% of tick-borne coinfections. One third may have concurrent human granulocytic anaplasmosis (HGA). Less common coinfection may occur with other tick-borne agents.

DIAGNOSIS HISTORY Few patients recall a tick bite. Patients live in or have recently traveled to an endemic region. Initial symptoms begin 1 to 4 weeks after the tick bite and are vague. They may include progressive fatigue, malaise, headaches, and anorexia, accompanied by intermittent fevers as high as 40°C.

Chills, myalgias, and arthralgias may follow these symptoms. Less common complaints include cough, sore throat, neck stiffness, abdominal pain, and emotional lability. PHYSICAL EXAM Fever and tachycardia are often the only findings. Mild conjunctival injection and pharyngeal erythema occasionally occur. Mild hepatomegaly and/or splenomegaly may be present. Jaundice or hematuria may also be observed. Petechiae and ecchymosis occur in rare cases, most often in the presence of severe illness with associated shock and/or DIC. DIFFERENTIAL DIAGNOSIS HGA Malaria Leptospirosis Sepsis associated with hemolytic anemia Noninfectious causes of hemolytic anemia Influenza Nonspecific viral syndrome DIAGNOSTIC TESTS & INTERPRETATION Giemsa or Wright thin blood smears may demonstrate the intraerythrocytic ring form: – This is often confused with the ring form of Plasmodium falciparum, the etiologic agent of malaria. – Rarely, the pathognomonic “Maltese cross” forms of the Babesia parasite may be seen on the blood smear. – Multiple smears should be performed as initial smears may be falsely negative early in the disease. Polymerase chain reaction (PCR) is highly sensitive and specific when available. Indirect immunofluorescent serology may help support or confirm the diagnosis. – Antigen-specific for B. microti – In endemic areas, the test has a sensitivity of 91% and a specificity of 99%. – Can be used when blood smears are negative – In general, a titer = 1:64 indicates exposure. – A 4-fold rise in antibody titer in acute and convalescent sera confirms the diagnosis. – Immunoglobulin levels decline rapidly within months of recovery. Other tests: Most of the abnormal routine test results are the result of hemolysis. Urinalysis – Proteinuria – Hemoglobinuria CBC – Normal leukocyte count/leukopenia – Normocytic/normochromic anemia – Thrombocytopenia

– Atypical lymphocytosis – Reticulocytosis Possible positive Coombs test Elevated ESR Liver function tests: elevated bilirubin, lactate dehydrogenase, and liver transaminases Elevated BUN and creatinine In asymptomatic patients, these tests are often normal. ALERT False negatives: Blood smears may not demonstrate the protozoa at low levels of parasitemia. Serologic false positives for B. microti include cross-reactivity with other Babesia sp. or malarial organisms. Serology titers may be low in the 1st week of symptoms.

TREATMENT GENERAL MEASURES Those with mild clinical disease usually recover without treatment. MEDICATION For asymptomatic patients who are otherwise healthy, treatment is only recommended if their babesial PCR or blood smear remains positive for more than 3 months. For symptomatic patients, treatment is generally for 7 to 10 days regardless of regimen; more severely ill patients may require a longer duration of therapy. First Line Atovaquone in combination with azithromycin – Has similar treatment effectiveness with fewer side effects (such as vertigo, tinnitus, and GI upset) than clindamycin and quinine Pediatric dosing: – Atovaquone 40 mg/kg/24 h PO every 12 hours (max 750 mg/dose) – Azithromycin 10 mg/kg/24 h (max 500 mg) PO on day 1 and 5 mg/kg/24 h (max 250 mg) PO once daily thereafter Adult dosing: – Atovaquone 750 mg PO every 12 hours – Azithromycin 500 to 1,000 mg PO on day 1 and 250 to 1,000 mg PO once daily thereafter Second Line Clindamycin in combination with quinine – Standard therapy for asplenic, immunodeficient, or severely ill patients – IV route for clindamycin is recommended for the severely ill patient. Pediatric dosing:

– Clindamycin: 20 to 40 mg/kg/24 h IV/PO divided every 6 to 8 hours (max 600 mg/dose) – Quinine: 24 mg/kg/24 h PO every 8 hours (max dose 650 mg/dose) Adult dosing: – Clindamycin: 600 mg PO every 8 hours or 300 to 600 mg IV every 6 hours – Quinine: 650 mg PO every 6 to 8 hours In areas endemic for Lyme disease and ehrlichiosis, consider adding doxycycline to either regimen until lab confirmation of absence of either disease in the patient with babesiosis. ADDITIONAL THERAPIES For life-threatening infections, exchange transfusion has been successful. Consider in patients with severe parasitemia (≥10%), severe hemolysis, or renal/hepatic/pulmonary compromise. Progressive respiratory distress may require mechanical ventilation. ALERT Signs to watch for: – Respiratory distress, especially after treatment has begun – Pancytopenia and lymphadenopathy: may indicate the development of hemophagocytic syndrome Pitfalls – Children who are from endemic areas and have an acute febrile illness may be misdiagnosed with a nonspecific viral illness. – One should be suspicious for a coinfection with Lyme disease or HGA in those who are not responding to standard therapy. – Delayed recognition of this uncommon disease may be life-threatening in the immunocompromised patient. – In endemic areas, babesiosis should be considered in a posttransfusion febrile illness in at-risk populations.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS When to expect improvement: Some improvement of symptoms should be noted within 24 to 48 hours of onset of therapy. Those who are only mildly affected usually have resolution of their symptoms over a few weeks. For severely affected and immunodeficient patients, the convalescent period may be as long as 18 months. In untreated asymptomatic individuals, parasitemia may persist for months to years. Long-term complications are rare. Recrudescence has been reported. COMPLICATIONS Rarely fatal in the United States Pancytopenia and overwhelming secondary bacterial sepsis may occur. Serious and fulminant complications have been described:

– Pulmonary edema and adult respiratory distress syndrome often happening after treatment has begun. – CHF – Renal failure – Hemophagocytic syndrome/DIC – Seizures/coma Those coinfected with Lyme disease are susceptible to more severe disease and complications.

ADDITIONAL READING American Academy of Pediatrics. Babesiosis. In: Kimberlin DW, Brady MT, Jackson MA, et al, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:253–254. Centers for Disease Control and Prevention. Surveillance for Babesiosis—United States, 2014 Annual Summary. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2016. Diuk-Wasser MA, Vannier E, Krause PJ. Coinfection by ixodes tick-borne pathogens: ecological, epidemiological, and clinical consequences. Trends Parasitol. 2016;32(1):30–42. Mukkada S, Buckingham SC. Recognition of and prompt treatment for tick-borne infections in children. Infect Dis Clin North Am. 2015;29(3):539–555. Sanchez E, Vannier E, Wormser GP, et al. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA. 2016;315(16):1767–1777. Vannier E, Krause PJ. Human babesiosis. N Engl J Med. 2012;366(25):2397–2407.

CODES ICD10 B60.0 Babesiosis

FAQ Q: How long does a tick have to be attached for infection to occur? A: In general, successful transmission requires at least 24 hours of attachment. Q: How should a tick be removed? A: The tick should be grasped with forceps as close to its head as possible and pulled straight up. If possible, it should be saved for identification. Wash the area with soap and water after removal. Q: Does infection confer lifetime immunity? A: No. Reinfection is possible.

BACK PAIN Kate Berz, DO Kelsey Logan, MD, MPH

BASICS DESCRIPTION Any condition causing pain of the thoracic, lumbar, or sacral spine EPIDEMIOLOGY 12-month period prevalence: 10–20% of children Lifetime prevalence: 12–50% PATHOPHYSIOLOGY Dependent on underlying cause Until skeletal maturity, partially ossified posterior column and vertebral body are weak points. Hyperextension with rotational spinal loading in the case of pars defects (e.g., spondylolysis or spondylolisthesis) Autoimmune or autoinflammatory processes as with juvenile idiopathic arthritis (JIA) or juvenile ankylosing spondylitis ETIOLOGY Unidentified in 50% of cases 30% of chronic cases (back pain >3 years) without clear etiology despite workup RISK FACTORS Poor conditioning or high athletic performance Joint hypermobility Role of backpack weight and style of wear undetermined Role of overweight or obesity yet to be determined GENERAL PREVENTION Back muscle strengthening and hamstring stretching exercises may be helpful. Maximum backpack load: 10–15% body weight Weight loss and increased physical activity in overweight or obese children 3 months off from sport per year, 1 day off from scheduled activity per week

DIAGNOSIS HISTORY History to elucidate most likely cause Musculoskeletal/trauma – Direct trauma

– Worsening pain after activity – Repetitive movements causing microtrauma Inflammatory – Morning stiffness (variable pain) – Pain/stiffness improves with movement. – Family history of rheumatic disease Infectious – Fever – Recent exposure to infection or tuberculosis (TB) – Recent illness Malignancy – Night sweats, fever, weight loss, malaise, pain waking at night – Previous history of malignancy – Severe, unrelenting pain despite supine position or adequate analagesia Neurologic – Radiating pain or foot drop – Loss of bowel or bladder function Endocrine/metabolic – Long-term steroid use – Vitamin D deficiency Psychosocial stressors (e.g., family coping mechanisms and response to pain and stress) Age differentiation – 10 years: pars defects, inflammatory disorders PHYSICAL EXAM Observe from behind patient: sacral dimple, vascular anomalies, posture, spinal curvature, anterior superior iliac spine (ASIS) height, limb length discrepancy, foot arch, lower limb alignment, rib rotation – Consider occult problem; mechanical or musculoskeletal problem – Scoliosis is rarely painful. – Increased fixed kyphosis of 40 degrees is indicative of Scheuermann disease. Palpate for point or focal tenderness along spine; sacroiliac (SI) joint tenderness – If bony tenderness present, consider fracture, vertebral osteomyelitis. – If paraspinal tenderness present, consider muscle strain; if SI tenderness, consider spondylitis or overuse. Assess range of motion: pain with spinal extension (causing strain of posterior elements of spine) – Consider spondylolisthesis (forward vertebral displacement), spondylolysis (pars interarticularis defect), fracture, vertebral osteomyelitis, or tumor. Assess range of motion: forward spinal flexion limitation – If painful, consider diskitis, vertebral osteomyelitis, vertebral body tumor, and herniated disk if pain radiates.

– If limited as noted by flattening of lumbosacral region with movement, consider spondylitis. Assess range of motion: restriction of spine with pain (especially with neck extension) and other associated joint abnormalities (swelling or pain/tenderness with limitation). If positive, consider JIA. Special tests: – Assess for pain with straight-leg raise: Consider tight hamstrings, psoas strain, or disk herniation if pain goes past the knees. – Assess for back pain with FABER (hip flexion, abduction, external rotation with foot on opposite knee) testing or direct palpation of SI joint: SI joint irritation or inflammation or hip etiology if hip pain – Assess for symmetric Achilles and patellar reflexes, sensation, Babinski (upper motor neuron), pain, and proprioception; deficits may indicate neuronal involvement; nerve testing: gastrocsoleus, L5 extensor hallucis longus, L4 to L5 tibialis anterior, L3 to L4 quadriceps, L2 to L3 hip flexors Abdominal or pelvic exam may be helpful. DIFFERENTIAL DIAGNOSIS Mechanical/trauma – Overuse injury – Disk herniation Direct trauma, contusion – Musculoskeletal strain in children with closed growth plates – Apophyseal ring fracture Structural – Pars defects: children usually >10 years of age – Spondylolysis/spondylolisthesis (anterior displacement/“slip” of vertebral body, evolution of bilateral spondylolysis) – Scheuermann kyphosis: deformity of thoracic spine associated with vertebral body wedging – Scoliosis: not usually associated with significant back pain – Backpack weight not clearly shown to correlate with back pain Inflammatory – JIA – Juvenile ankylosing spondylitis – Chronic recurrent multifocal osteomyelitis Neoplastic – Ewing sarcoma – Lymphoma, leukemia Infectious – Osteomyelitis – Epidural abscess – Pyelonephritis – Diskitis Endocrine/metabolic – Osteoporosis

– Vitamin D deficiency Other – Pain amplification syndrome (fibromyalgia, myofascial pain) – Sickle cell crises, abdominal disease (pancreatitis, pyelonephritis) DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Tests: CBC with differential, sedimentation rate, C-reactive protein (CRP), and comprehensive metabolic panel with uric acid and LDH – Significance: malignancy, infection, inflammatory Antinuclear antibody, rheumatoid factor, anticyclic citrullinated antibody, and HLA-B27 only if obvious other associated joint abnormalities found – Significance: inflammatory/autoimmune disorders Cultures, PPD, or other TB study – Significance: infection 25(OH)D, PTH, calcium, phosphorus, alkaline phosphatase – Significance: vitamin D deficiency or rickets Abnormal exam/history or focal symptoms warrant imaging. Plain radiographs if trauma, bony tenderness, 3 to 4 weeks of pain – AP and lateral; oblique (if warranted) of the spine, standing full AP spine for curve – Assess for fracture, osteomyelitis, and masses. – Intra-articular pars defect commonly in L4/L5 indicates spondylolysis. – Bilateral pars defect with anterior vertebral body displacement indicates spondylolisthesis. Bone scan with single photon emission CT (SPECT) – Occult/subtle bony lesions, stress fractures, spondylolysis, and spondylolisthesis Plain CT spine: rarely used – Osteoid osteoma, unstable fracture MRI – Tumor, infection, diskitis, disk injuries, synovitis (including effusions or erosions—with contrast), and neurologic findings – Becoming test of choice for spondylolysis requires specific protocol. ALERT Warning signs of potentially serious causes of back pain in children include the following: Young age: 4 weeks Acute trauma Night pain, fever, weight loss, or malaise Abdominal mass Early morning stiffness History of tumor Exposure to TB Limp

Chronic interference with normal activity (e.g., school, sports, play) Postural changes causing scoliosis or kyphosis Other associated joint abnormalities (swelling OR pain/tenderness with joint limitation)

TREATMENT GENERAL MEASURES If no warning signs, conservative management with nonsteroidal anti-inflammatory drugs (NSAIDs) and relative rest (avoiding activities that cause or increase pain) Supervised exercise programs through home exercises or physical therapy have moderate evidence of effectiveness for low back pain without apparent anatomic cause. Close follow-up is appropriate. Spondylolysis: Compliance with relative rest from offending activities is variable and should be addressed to improve adherence; there is evidence that more relative rest, up to 3 months, improves outcome. Diskitis: antistaphylococcal coverage Bed rest/activity limitation: Adult data do not support this strategy. MEDICATION NSAIDs for overuse, sprains, or strains in adolescents and for patients with arthritis Additional medication may be necessary depending on underlying condition such as antibiotics for infection, chemotherapy for malignancy, immunosuppression for inflammatory/autoimmune, or vitamin D and calcium supplementation for vitamin D deficiency or osteoporosis. Oral steroids are not considered effective treatment for acute or chronic back pain. ISSUES FOR REFERRAL Sports medicine or orthopedics appropriate with Scheuermann disease, spondylolysis, or spondylolisthesis Concern for malignancy or long-standing inflammatory process such as JIA or juvenile ankylosing spondylitis warrants referral to hematology/oncology or rheumatology, respectively. Endocrinology referral for suspected osteoporosis ADDITIONAL THERAPIES Physical therapy or a home exercise program with focus on core strength and flexibility is helpful in most cases. For overuse injuries, removal from activity with slow gradual return Structural problems such as spondylolysis, spondylolisthesis, and Scheuermann disease often respond to rest, ice, and NSAIDs. Thoracolumbar bracing has not been shown to improve healing or time back to full activity but may be used for pain control if needed. Biopsychosocial approach is needed for patients with pain amplification syndromes in conjunction with physical and cognitive behavioral therapies and emphasis on functionality.

COMPLEMENTARY & ALTERNATIVE THERAPIES Yoga and Pilates emphasizing core strength and flexibility may be useful in the adolescent. Cochrane systematic review determined massage may be useful in the setting of acute or subacute back pain in adults. Acupuncture has been shown to be safe and may be effective for low back pain. SURGERY/OTHER PROCEDURES May be indicated in patients with spondylolisthesis of >50% Epidural steroid injection for lumbar disk herniation is safe in children and adolescents; efficacy is variable.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patients managed conservatively should be reevaluated within 2 weeks and then visits spaced further out as their pain improves. If symptoms not improving with conservative measures, then consider workup as outlined and appropriate referral depending on results. Patient Monitoring No specific lab tests need to be routinely followed. PATIENT EDUCATION Patients and families need to be aware that musculoskeletal and structural causes may take several weeks or months to heal. Bony healing in spondylolysis is not correlated with clinical outcome in many cases. Patients should be told to report changes in symptoms, especially any red flags. Higher body mass index (BMI) has been associated with low back pain; weight counseling in overweight or obese patients may be of benefit. PROGNOSIS Dependent on the underlying cause With proper diagnosis and treatment, the majority do well, without significant sequelae. Muscular or functional back pain often abates as biomechanical issues are corrected through rehab. Bony fractures and stress fractures: Expect to take normal bony healing course with appropriate treatment. COMPLICATIONS Weakness in core and hip muscles Paralysis, other permanent neuromuscular injury Chronic back pain or development of pain amplification syndrome

ADDITIONAL READING

Agabegi SS, Kazemi N, Sturm PF, et al. Natural history of adolescent idiopathic scoliosis in skeletally mature patients: a critical review. J Am Acad Orthop Surg. 2015;23(12):714–723. Brenner JS; for American Academy of Pediatrics Council on Sports Medicine and Fitness. Overuse injuries, overtraining, and burnout in child and adolescent athletes. Pediatrics. 2007;119(6):1242– 1245. Furlan AD, Imamura M, Dryden T, et al. Massage for low back pain: an updated systematic review within the framework of the Cochrane Back Review Group. Spine (Phila Pa 1976). 2009;34(16):1669– 1684. Hershkovich O, Friedlander A, Gordon B, et al. Associations of body mass index and body height with low back pain in 829,791 adolescents. Am J Epidemiol. 2013;178(4):603–609. Jackson C, McLaughlin K, Teti B. Back pain in children: a holistic approach to diagnosis and management. J Pediatr Health Care. 2011;25(5):284–293. Michaleff ZA, Kamper SJ, Maher CG, et al. Low back pain in children and adolescents: a systematic review and meta-analysis evaluating the effectiveness of conservative interventions. Eur Spine J. 2014;23(10):2046–2058. Shah SA, Saller J. Evaluation and diagnosis of back pain in children and adolescents. J Am Acad Orthop Surg. 2016;24(1):37–45. Taxter AJ, Chauvin NA, Weiss PF. Diagnosis and treatment of low back pain in the pediatric population. Phys Sportsmed. 2014;42(1):94–104. Tsirikos AI, Garrido EG. Spondylolysis and spondylolisthesis in children and adolescents. J Bone Joint Surg Br. 2010;92(6):751–759.

CODES ICD10 M54.9 Dorsalgia, unspecified M54.6 Pain in thoracic spine M54.5 Low back pain

FAQ Q: Which children with back pain should have activity restriction? A: Activities should be able to be performed with normal mechanics (no limping or adjustment of skills due to pain). Resting is indicated if this is not possible. Workup and ultimate diagnosis will determine further activity restriction. Q: When can/should the child resume activities after an acute back injury? A: Children with a normal neurologic exam, normal range of motion, and normal strength may resume tolerable activities if diagnostic studies are normal. Q: Should a trial of steroids be used to rule out inflammatory back pain? A: Pain improvement with glucocorticoids may suggest an inflammatory condition but is not diagnostic. It is not recommended in children. It can often complicate the clinical picture, as noninflammatory back pain will sometimes respond to treatment as well.

BAROTITIS Judith Brylinski Larkin, MD, FAAP

BASICS DESCRIPTION Barotrauma of the middle or inner ear, most commonly caused by flying in an airplane or scuba diving but also caused by travel in elevators and travel to high altitudes May also be seen in those who have used a hyperbaric oxygen chamber and in people involved in explosions—blast injuries Referred to as “middle ear squeeze” by scuba divers EPIDEMIOLOGY Severe disease is uncommon in commercial aircraft because of pressurization. Significant disease is more common in scuba divers, in those who fly military aircraft, and during use of hyperbaric oxygen chambers. There is wide variation, with studies reporting an incidence of 8–55% for children after a single flight. Most studies agree that the incidence is ~20% in adults after a single flight. 40% frequency in scuba diving RISK FACTORS Age: Infants or toddlers are at higher risk because of small eustachian tubes. Disease states that impede normal eustachian tube function: otitis media, upper respiratory tract infection (URI), allergic rhinitis Smoking Vigorous use of Valsalva maneuver GENERAL PREVENTION Gradual descent during scuba diving—never rapid When ascending, divers should avoid rising more quickly than their air bubbles. Yawning, swallowing, chewing, or doing Valsalva maneuver during takeoff and landing in planes and during ascent and descent when scuba diving Gentle Valsalva—never vigorous Avoid flying or diving when you have a URI or allergic rhinitis. Avoid sleeping on plane during takeoff and landing. Break seal of wet suit hood to allow water to fill external canal before descent. Avoid use of earplugs. PATHOPHYSIOLOGY Boyle’s law states that as pressure of a gas decreases, volume increases, and as pressure of a gas increases, volume decreases. Ambient pressure decreases during airplane/scuba diving ascent and increases during descent.

During ascent, the tympanic membrane (TM) bulges outward and the eustachian tube vents the excess middle ear pressure. Pressure is easily equalized. During descent, the TM bulges inward and the eustachian tube resists inward flow of air. Pressure equalization is difficult. At a pressure differential of 60 mm Hg (greater ambient to middle ear pressure), subjective discomfort is reported. At a pressure differential of 90 mm Hg, the eustachian tube collapses and becomes obstructed. Autoinflation is unsuccessful. TM can rupture at pressure differentials >100 to 400 mm Hg. Barotitis is sometimes classified using Teed classification of disease severity (see “Physical Exam”). ETIOLOGY Differences in the atmospheric pressure between the inner ear, middle ear, and environment result in injury to the middle and/or inner ear.

DIAGNOSIS HISTORY Ear pain, pressure sensation, diminished hearing Symptoms of inner ear damage may include vestibular and/or auditory complaints including tinnitus, vertigo, nausea, and vomiting. History of recent airplane flying, scuba diving, or hyperbaric oxygen chamber use PHYSICAL EXAM Nystagmus Hearing loss Teed classification to describe appearance of the TM: – Grade 0: symptoms without physical signs – Grade 1: diffuse redness and retraction of TM – Grade 2: grade 1 plus slight hemorrhage into TM – Grade 3: grade 1 plus gross hemorrhage into TM – Grade 4: bulging TM with air–fluid level, blood in TM – Grade 5: free hemorrhage into TM and ear canal with perforation of TM DIFFERENTIAL DIAGNOSIS Otitis media with effusion Acute otitis media Otitis externa Blunt trauma to the TM Exposure to extremely loud noise DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging)

CT of the inner ear may be indicated in patients with vestibular symptoms or hearing loss to rule out inner ear damage. Diagnostic Procedures/Other Hearing tests should be performed on all patients who have signs of barotrauma and on patients with normal physical exams but who are symptomatic.

TREATMENT GENERAL MEASURES Valsalva maneuver (blowing the nose while pinching the nostrils closed) may be helpful when diving or descending and will force air into the middle ear via the eustachian tube, thereby equalizing the pressure between the middle ear and the environment. This should be done gently. Swallowing, yawning, and chewing can help to release pressure through the eustachian tube when descending in an airplane or when returning to the water surface while scuba diving. Politzer bag: instrument used for clearing pressure disequilibrium that has not improved with Valsalva maneuvers and a trial of decongestants Otovent: Another instrument that may be used for treatment or prevention; usage can be taught to children as young as 2 to 6 years of age. Myringotomy with or without tubes may be required to relieve pressure in severe disease. It may also be used as a preventive measure in those with a history of barotitis. Myringotomy is effective for the patient with excruciating pain or unrelenting eustachian tube dysfunction; this is best performed by an otolaryngologist. MEDICATION Nasal decongestant sprays (oxymetazoline [Afrin®]) – Have been reported by some to be helpful, but a randomized clinical trial showed no advantage over placebo – Theory: By constricting mucosal arterioles, eustachian tube function is enhanced. – Topical decongestants are used 1 hour prior to plane travel/diving and 1/2 hour prior to plane descent. – 2 drops/sprays per nostril – Use in children >6 years of age. Oral decongestants – Two randomized controlled trials suggest that oral decongestants may be effective, although a trial in children did not show a beneficial effect. – May be helpful through the same physiologic pathway as topical agents – Should be initiated 1 to 2 days prior to the expected pressure change Antihistamines – May also be helpful by reducing mucosal edema and enhancing the eustachian tube orifice – Can be used on the day of the expected pressure change Nasal surfactants may be useful, but ongoing studies are needed.

Pain relievers such as acetaminophen, ibuprofen, and naproxen may be useful for severe pain. SURGERY/OTHER PROCEDURES Rarely, myringotomy with or without tube insertion is required to relieve pressure and pain as well as prevent complications. Myringotomy is a surgical procedure where a small incision is made in the TM. This opens the middle ear space and equalizes the pressure on both sides of the TM. Myringotomy without tube insertion will relieve pressure, but the opening may close very quickly and may not allow time for the barotrauma to heal; on occasion, myringotomy with tube insertion is necessary. Tympanostomy tubes are not appropriate for scuba divers.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patient Monitoring Most patients with barotitis can be managed conservatively. Those with complications noted earlier require specialist referral. PROGNOSIS Complete spontaneous resolution in mild cases Middle ear barotrauma is usually self-limited and correctable with the techniques described in the “General Measures” section. In rare instances, where there is severe pain or eustachian tube dysfunction, myringotomy with or without tube insertion will relieve the pressure differential. Pressure differential without damage to the middle or inner ear usually resolves within a few days of returning to normal atmospheric pressure. Barotitis that results in injury to the middle or inner ear has a variable rate of improvement; some damage may be permanent (e.g., that to the organ of Corti), whereas other injury is reversible (e.g., that involving the TM). Variable outcome for auditory and vestibular symptoms and injuries to the inner ear COMPLICATIONS Vertigo Tinnitus Hearing loss TM rupture Oval or round window rupture Hemorrhage

ADDITIONAL READING Buchanan BJ, Hoagland J, Fischer PR. Pseudoephedrine and air travel-associated ear pain in children. Arch Pediatr Adolesc Med. 1999;153(5):466–468. Janvrin S. Middle ear pain and trauma during air travel. Clin Evid. 2002;7:466–468. Jones JS, Sheffield W, White L, et al. A double-blind comparison between oral pseudoephedrine and

topical oxymetazoline in the prevention of barotrauma during air travel. Am J Emerg Med. 1998;16(3):262–264. Mirza S, Richardson H. Otic barotrauma from air travel. J Laryngol Otol. 2005;119(5):366–370. Rosenkvist L, Klokker M, Katholm M. Upper respiratory infections and barotraumas in commercial pilots: a retrospective survey. Aviat Space Environ Med. 2008;79(10):960–963. Stangerup SE, Klokker M, Vesterhauge S, et al. Point prevalence of barotitis and its prevention and treatment with nasal balloon inflation: a prospective, controlled study. Otol Neurotol. 2004;25(2):89– 94. Weiss MH, Frost JO. May children with otitis media with effusion safely fly? Clin Pediatr (Phila). 1987;26(11):567–568.

CODES ICD10 T70.0XXA Otitic barotrauma, initial encounter H92.09 Otalgia, unspecified ear H93.19 Tinnitus, unspecified ear

FAQ Q: Is the Valsalva maneuver also effective on plane ascent? A: Yes. Creating even greater pressure in the middle ear by performing the Valsalva maneuver can overcome a resistant eustachian tube and result in sudden venting of increased middle ear pressure. Q: Can children with otitis media travel in airplanes? A: Yes. Weiss and Frost (1987) have shown that commercial air travel did not result in worsening of symptoms and, in fact, the presence of otitis media with effusion seemed to be protective against barotitis. Q: How can I minimize my child’s ear pain when traveling in an airplane? A: For infants: Have them nurse, take a bottle, or suck on a pacifier during ascent and descent. Older children may eat or chew gum or suck on hard candies. This will result in pharyngeal movements that will repeatedly open the eustachian tube and equalize middle ear pressure to environmental pressure. Children can also be taught the Valsalva maneuver. If the child is currently experiencing a URI, use of decongestants prior to flight may be helpful.

BELL PALSY Stephen J. Falchek, MD

BASICS DESCRIPTION This paralysis may involve all of the modalities affected by the 7th cranial nerve: – Mimetic facial movement – Taste – Cutaneous sensation – Hearing acuity – Lacrimation – Salivation The most important feature in diagnosis and management of Bell palsy is the distinction between a peripheral and a central 7th nerve palsy. EPIDEMIOLOGY Incidence Annually, incidence ranges from 3/100,000 in patients 2 millennia, suggesting formation of bezoars may have been/still be culturally important for certain societies EPIDEMIOLOGY Phytobezoars occur almost exclusively in adults. 90% of trichobezoars occur in female patients 20% of the total bilirubin) may be elevated as early as the first 24 hours of life. Additional laboratory findings may include mild to moderate elevations in AST, ALT, and alkaline phosphatase as well as significant elevations in γ-glutamyltransferase (GGT) Additional diagnostic testing should be done as clinically indicated. Bacterial cultures (blood, urine, stool), viral studies (hepatitis B, hepatitis C, Epstein-Barr virus, TORCH infections, HIV, adenovirus, enterovirus) Metabolic profiles (plasma amino acids, urine organic acids and urine succinylacetone, lactate/pyruvate ratio) Serum α1-antitrypsin level and phenotype Thyroid function tests (TSH, free T4) Urine-reducing substances to evaluate for galactosemia (if infant has taken breast milk or lactosecontaining formula) CBC, coagulation studies (prothrombin time/international normalized ratio/partial thromboplastin time [PT/INR/PTT]), total protein, albumin, and fat-soluble vitamins Abdominal ultrasound – Should be obtained to rule out choledochal cyst but has poor sensitivity and specificity for BA unless “triangular chord” sign seen (80% sensitive, 98% specific) – May also assist in defining embryonal versus perinatal form Hepatobiliary iminodiacetic acid (HIDA) scan/hepatobiliary scintigraphy can be obtained to evaluate biliary excretion. Follow-up Tests & Special Considerations Discussion with pediatric gastroenterologist should be obtained following evidence of persistent cholestasis. Liver biopsy: In BA, findings may include: – Bile duct proliferation – Bile stasis – Periportal inflammation – Periportal fibrosis Sweat chloride test (cystic fibrosis) Ophthalmology exam to assess for Alagille syndrome (posterior embryotoxon) and congenital infections Spine film to evaluate butterfly vertebrae of Alagille syndrome Echocardiogram to evaluate cardiac anomalies in Alagille syndrome Urine bile acid analysis Intraoperative cholangiogram – Gold standard for diagnosis of BA but is an invasive test – Reserved for individuals with high suspicion of BA

TREATMENT

SURGERY/OTHER PROCEDURES A hepatoportoenterostomy (Kasai procedure) – The Kasai procedure is the only effective therapy for BA other than a liver transplant. – The goal of the Kasai procedure is to restore bile flow from the liver to the intestine. Despite the Kasai procedure, 70–80% of patients with BA ultimately require liver transplantation. – At 3 months after Kasai procedure, a total serum bilirubin 14 years old complain of LUTS. RISK FACTORS Recurrent UTIs Constipation GENERAL PREVENTION Daily soft, formed bowel movements Timed voiding—goal between 5 to 7 times a day PATHOPHYSIOLOGY

A child who is holding his or her stool and not having regular daily bowel movements has increased stool in the rectal vault. As stool builds up in the rectal vault (constipation), it begins to push on the bladder. This process causes decreased bladder filling. In addition, the rectal vault shares sensory input with the bladder in the same spot of the sacral spinal cord, and the full rectal vault can be confused at this level and trigger bladder spasms, leakage, and/or incomplete emptying of the bladder. As a child struggles to stay dry in the face of bladder spasms, he or she overcontracts the external sphincter of the bladder, has a hard time relaxing the external sphincter during voiding, and develops increased pressure during voiding. This increased pressure can be transmitted to the kidneys. ETIOLOGY The etiology of BBD is broad and can have multiple causes. Increased rectal volume will mechanically compress the bladder and decrease bladder capacity and cause urgency and frequency. This can also change the neural stimuli in the bladder and the pelvic floor muscles leading to decreased urge to evacuate, poor coordination of the sphincter and the bladder muscles, increased residuals, and decreased awareness of evacuation leading to stool and bladder accidents. COMMONLY ASSOCIATED CONDITIONS ADHD Autism spectrum disorder

DIAGNOSIS HISTORY A child will present after toilet training with symptoms of daytime and/or nighttime incontinence. In addition, he or she may have a history of recurrent UTIs or VUR. Bowel dysfunction may present as encopresis, constipation, or as fecal impaction. It is important to know frequency of voiding, maximum and average bladder volumes, fluid intake. Symptoms of urgency, holding maneuvers, dribbling or straining to urinate Change in gross motor coordination in the lower extremities; that is, new clumsiness or falling (tethered cord) Birth history or trauma during birth, neurodevelopmental delay Family conflict or social stressors History of urologic or renal disorders Define constipation using the Rome III criteria PHYSICAL EXAM Most commonly, the exam will be normal. Abdomen: palpable bladder or stool in the colon Evaluate the spine for skin discoloration, dimples, or hair patches to rule out occult spinal dysraphism. Evaluate female genitalia and rule out labial adhesions that can trap urine and cause incontinence.

Consider possible ectopic ureter if there is vaginal pooling of urine. Evaluate male genitalia and rule out prior hypospadias repair or severe phimosis in which urine trapping can occur as a result of urethral strictures. Rectal exam can reveal fecal impaction. DIFFERENTIAL DIAGNOSIS Ectopic ureter to the vagina Spinal cord abnormalities (tethered cord) Brain tumors Urethral strictures DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Voiding drinking diary over 3 days has a lower false negative rate for frequency compared to a 2-day diary. Dysfunctional Voiding Symptom Score helps guide response to treatment. Short Screening Instrument for Psychological Problems in Enuresis Urinalysis to rule out bacteriuria or glucosuria First morning urine osmolality to assess renal concentrating ability in nocturnal enuresis Follow-Up Tests & Special Considerations Radiograph of kidneys, ureters, and bladder (KUB): constipation, normal spine Renal US: pre- and postvoid images to evaluate the bladder and kidneys Pelvic US to measure the transverse radius of the rectum if >3 cm is indicative of rectal fecal impaction. Diagnostic Procedures/Other Uroflow with EMG and PVR is noninvasive and can be helpful in more recalcitrant cases to better define synergy of the sphincter during voiding Voiding cystourethrogram (VCUG) – Used to evaluate for VUR and to look at the urethra and bladder neck during voiding – Only to be done in cases with multiple febrile UTIs Urodynamic studies – Tools used to define bladder function if there is a poor response to initial management – Uroflow is used to evaluate bladder outflow. – Cystometry and perineal EMG studies give information about bladder function during filling and voiding. Test Interpretation Children with severe BBD may need to go on for MRI testing of the spine to rule out tethered cord, in these scenarios the children will have abnormal urodynamic studies and potential VCUG/RBUS with thickened bladder wall, trabeculations +/− hydronephrosis, and/or VUR.

TREATMENT

GENERAL MEASURES Behavior modification Educate proper voiding mechanics. Timed voiding every 2 hours; may use a watch with a repeating alarm Correct sitting and standing positions during voiding Modify drinking and voiding habits based on diaries to attain frequent voiding and regular stooling. Encourage plenty of water intake; fiber for management of constipation Time set aside to attempt regular morning bowel movements When a provider is treating a child with BBD, it is imperative that the focus begins with daytime management first, specifically focusing on soft daily bowel movements and timed voiding. The nighttime wetting will not improve until the daytime wetting and the constipation have been properly managed. MEDICATION First line: bowel management – Goal: full clean out Clean out usually lasts 3 days. Use polyethylene glycol 3350 (MiraLax®)/lactulose and enemas and/or mineral oil. – If severe, can use KUB to confirm clean out is complete Daily management – Goal: 1 to 2 soft bowel movements daily – Polyethylene glycol 3350 (MiraLax®)/lactulose daily dosing and/or mineral oil help for daily maintenance. Consider a referral at this point if no progress. Second line: antimuscarinics – Are used for overactive bladders – Work by reducing the frequency and intensity of the bladder contraction – Can be supplied in short-acting and long-acting formulas or transdermally – Constipation is a potential side effect. Third line: mirabegron – Targets smooth muscle in the bladder to help with relaxation – Promotes bladder storage – Hypertension is a possible side effect. ALERT Make sure the patient has truly had a good bowel clean out and is focusing first on one to two daily soft bowel movements before adding medications to treat the bladder symptoms. ISSUES FOR REFERRAL If a child’s symptoms do not respond to a bowel clean out and daily maintenance then consider referral to pediatric urology. If a child has had multiple febrile UTIs then consider referral to pediatric urology.

ADDITIONAL THERAPIES Biofeedback Physical therapy Acupuncture Botox Neuromodulation SURGERY/OTHER PROCEDURES A pediatric urologist will be crucial in deciding whether or not a child should move forward with more invasive testing such as urodynamics and whether or not a child should have an MRI to rule out tethered cord. Sacral neuromodulation and botulinum A are also used as an intervention for children with refractory urge incontinence after failure of more standard therapies. COMPLEMENTARY & ALTERNATIVE THERAPIES Transcutaneous posterior tibial nerve stimulation and parasacral transcutaneous neuromodulation have shown improvement in bladder volumes, overactivity, and dysfunctional voiding scores. However, it is still unknown how many treatments and for how long a child may require the therapy. ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS Nursing education regarding bowel clean outs and daily bowel management are crucial. A nurse can make all the difference between a child staying cleaned out and on a good maintenance course to one who does not stay cleaned out.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patient Monitoring Patients need follow-up around 1 month after commencing treatment of the constipation, at that point, improvement in the LUTS becomes evident. They need reminding that a good bowel cleanout and maintenance of the bowel function needs to go on consistently for 3 to 6 months before there is persistent change. They also need reminding of a good timed voiding schedule. DIET Optimal hydration is key to good bladder cycling and avoiding constipation. Increased fiber intake and physical activity also help with preventing constipation. PATIENT EDUCATION Mobile apps for tracking voiding and drinking diaries may be helpful. PROGNOSIS 80% of children are able to resolve their symptoms, with attention given to their bowel function and timed voiding. Because this treatment predominantly involves making behavioral changes, this process does not occur

quickly. Time and patience are required by both the parents and the children. COMPLICATIONS Children with recurrent febrile UTIs should be referred to pediatric urology. Children with abnormal renal US should be referred to pediatric urology. Children who don’t resolve their incontinence after initial management of the bowel dysfunction should be referred to pediatric urology.

ADDITIONAL READING Austin P, Bauer S, Bower W, et al. The standardization of terminology of lower urinary tract function in children and adolescents: update report from the Standardization Committee of the International Children’s Continence Society. Neurourol Urodyn. 2016;35(4):471–481. Dohil R, Roberts E, Jones KV, et al. Constipation and reversible urinary tract abnormalities. Arch Dis Child. 1994;70(1):56–57. Issenman RM, Filmer RB, Gorski PA. A review of bowel and bladder control development in children: how gastrointestinal and urologic conditions relate to problems in toilet training. Pediatrics. 1999;103(6, Pt 2):1346–1352. Koff SA, Wagner TT, Jayanthi VR. The relationship among dysfunctional elimination syndromes, primary vesicoureteral reflux and urinary tract infections in children. J Urol. 1998;160(3, Pt 2):1019– 1022. Loening-Baucke V. Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood. Pediatrics. 1997;100(2, Pt 1):228–232. Santos JD, Lopes RI, Koyle MA. Bladder and bowel dysfunction in children: an update on the diagnosis and treatment of a common, but underdiagnosed pediatric problem. Can Urol Assoc J. 2017;11(1–2 Suppl 1):S64–S72. Van Hoecke E, Baeyens D, Vanden Bossche H, et al. Early detection of psychological problems in a population of children with enuresis: construction and validation of the Short Screening Instrument for Psychological Problems in Enuresis. J Urol. 2007;178(6):2611–2615.

CODES ICD10 R32 Unspecified urinary incontinence K59.00 Constipation, unspecified R15.9 Full incontinence of feces

FAQ Q: Should children with BBD have urodynamic evaluation? A: Rarely. A patient should undergo standard therapy with timed voiding and treatment of constipation as the 1st-line therapy. If that fails, then a referral to pediatric urology is appropriate and the need for further testing will be assessed. Q: Will the child outgrow this?

A: 66% of children had improvement of the daytime and nighttime symptoms with management of the bowel function alone and up to 89% of all children will respond well to education also known as urotherapy and bowel management. Q: How many children with BBD have psychological comorbidities? A: In a recent study it was found that 51% of children with BBD had an adverse childhood encounter compared to only 25% of children with a neuropsychiatric disorder. One should consider screening and possible referral of these children for psychological counseling to aid with treatment. The “Short Screening Instrument for Psychological Problems in Enuresis” is one screening questionnaire that can be helpful.

BLASTOMYCOSIS Evan J. Anderson, MD

BASICS DESCRIPTION Systemic infection caused by the dimorphic soil fungus Blastomyces dermatitidis Dimorphism is characterized by a mold phase (mycelial form) that grows at room temperature and a yeast form that grows at body temperature. Incubation period estimated at 30 to 45 days EPIDEMIOLOGY Similar to other dimorphic fungi, B. dermatitidis is a soil saprophyte (mycelial form). Congenital infections occur rarely. Infection is endemic in the Upper Midwest and Southern United States, particularly in the wooded Mississippi and Ohio River valleys and the Great Lakes. The highest incidence in the United States is in Wisconsin, Mississippi, and Tennessee followed by Minnesota, Illinois, North Dakota, Alabama, and Louisiana. Substantial disease occurs in the Canadian provinces of Manitoba and northwestern Ontario. Other reported areas of infection include Africa, India, and South America. Children account for 3–11% of all cases of blastomycosis. Blastomycosis is a very uncommon diagnosis even in endemic regions. RISK FACTORS Blastomycosis is more common in males. This is thought to be due to occupational or recreational activities that increase risk of exposure. Underlying immunodeficiency is rarely observed among children with blastomycosis. GENERAL PREVENTION No special precautions for hospitalized patients are indicated. The natural reservoir is undetermined. PATHOPHYSIOLOGY Inhalation of the fungus into the lung is followed by an inflammatory response with neutrophils and macrophages. Blastomycosis most commonly presents as subacute pulmonary disease, but the clinical spectrum of the disease extends from asymptomatic to disseminated disease that can involve lung, skin, bone, and central nervous system (CNS). As many as 50% of infections are asymptomatic. ETIOLOGY Infection is almost always caused by inhalation of spores from B. dermatitidis. Rarely, blastomycosis has occurred through accidental inoculation, dog bites, conjugal transmission,

and intrauterine transmission. Point-source outbreaks have occurred with occupational and recreational activities that occur in areas with moist soil and decaying vegetation, such as along streams and rivers. Natural infection occurs in humans and dogs. COMMONLY ASSOCIATED CONDITIONS Pulmonary blastomycosis – Most common form of infection by Blastomyces in children – Can be acute, subacute, or chronic – Illness severity can vary greatly, from asymptomatic to upper respiratory tract infection, bronchitis, pleuritis, pneumonia, or severe respiratory distress. Cutaneous blastomycosis – Skin manifestations are variable and include nodules, verrucous lesions, subcutaneous abscesses, or ulcerations. – Cutaneous disease usually occurs after pulmonary infection with dissemination to the skin, rarely by direction inoculation. Bone blastomycosis – Bone disease usually occurs after pulmonary infection with dissemination to the bone resulting in osteomyelitis and bone destruction. Disseminated blastomycosis – Recent series suggest that this occurs in 2 weeks) nonproductive cough – Pleuritic chest pain – Poor appetite – May also be a history of fever, chills, weight loss, fatigue, night sweats, or, rarely, hemoptysis

PHYSICAL EXAM Initial pulmonary infection may present with physical exam findings similar to those of bacterial pneumonia. Respiratory signs and symptoms often have resolved by the time cutaneous manifestations are apparent. Skin involvement appears as nodules, nodules with ulceration, or granulomatous lesions. Bone involvement usually presents with progressive focal pain and point tenderness. DIFFERENTIAL DIAGNOSIS Acute bacterial infection Neoplasm Tuberculosis Sarcoidosis Other fungal infections causing pneumonia (e.g., histoplasmosis) DIAGNOSTIC TESTS & INTERPRETATION Diagnostic Procedures/Other Definitive diagnosis requires the growth of B. dermatitidis from a clinical specimen. In the cooler temperature at which fungal culture is performed in the laboratory, B. dermatitidis usually switches back to the mold form. Direct visualization of the yeast form may be performed on samples of sputum, urine, cerebrospinal fluid (CSF), bronchoalveolar lavage sample, or tissue biopsy. Although the most accurate serologic test is the enzyme immunoassay, all serologic tests have poor sensitivity and specificity. An assay to detect Blastomyces antigen in urine is available and is about 93% sensitive. The sensitivity of the urinary antigen is lower in extrapulmonary disease. Cross-reactivity occurs in patients with histoplasmosis, paracoccidioidomycosis, and Penicillium marneffei infections. Blastomycosis can also cause a false positive Histoplasma urinary antigen. Chest radiography commonly reveals lobar consolidation. Cavitation, fibronodular patterns, mass, and mass effect may also be seen.

TREATMENT MEDICATION First Line Although acute pulmonary infections may resolve without treatment, the high rate of progression to extrapulmonary disease leads many experts to recommend treatment for all cases of blastomycosis. Mild or moderate pulmonary or extrapulmonary disease – Oral itraconazole – Alternative agents include fluconazole or voriconazole. Severe pulmonary disease, other severe infection, or immunosuppression – IV amphotericin B: Many experts prefer a lipid formulation of amphotericin B over amphotericin B deoxycholate.

– Therapy may be switched to oral itraconazole after clinical stabilization with amphotericin B. CNS blastomycosis – Lipid formulation of amphotericin B at 5 mg/kg/24 h over 4 to 6 weeks, followed by an oral azole During pregnancy – IV amphotericin B – Azoles should be avoided owing to potential teratogenicity. Length of therapy is site dependent: – ≥6 months or longer for pulmonary disease – ≥12 months or longer for bone or CNS disease Lifelong suppressive therapy with oral itraconazole may be required for immunosuppressed patients and in patients who experience relapse despite appropriate therapy. Second Line Voriconazole, a newer azole, has in vitro activity against B. dermatitidis and penetrates the CSF better than itraconazole. Anecdotal reports support its use as an option for step-down therapy for CNS infection. ISSUES FOR REFERRAL Follow-up should occur with an infectious disease specialist until therapy is completed. SURGERY/OTHER PROCEDURES Occasionally, drainage of abscesses and debridement of bone are necessary.

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patient Monitoring All azoles can cause hepatitis. Thus, hepatic enzymes should be measured before starting therapy, 2 to 4 weeks after therapy has begun, and every 3 months during therapy. All azoles interact with P450 enzymes. Consider drug–drug interactions when the patient is taking other medications. Itraconazole capsules are poorly absorbed; the oral solution is poorly tolerated due to taste. Monitoring adherence to therapy is important and many recommend following itraconazole levels. Amphotericin B commonly causes acute kidney injury and electrolyte wasting (particularly potassium and magnesium). Infusion-related toxicity is also common. Lipid formulations are typically better tolerated than the deoxycholate. The Blastomyces urinary antigen has been used to monitor response to therapy. PROGNOSIS Before antifungal medications were available, the mortality associated with blastomycosis was up to 90%. Appropriate treatment with antifungal medications results in excellent cure rates and mortality rates of matched familial > unrelated. – Matched unrelated donor: >18 million potential donors registered worldwide. Disadvantages include long search time (2 to 3 months), lower chance of finding an 8/8 match for minorities, increased risk of graft failure and GVHD, and slower immune reconstitution. – Alternative donors include mismatched unrelated donor (match at ≥7/8 HLA Ag), umbilical cord blood (match at ≥4/6 HLA Ag), or haploidentical (related) donor (2 mg/dL); painful hepatomegaly; or ascites ± weight gain of >2% from baseline Baltimore criteria: bilirubin >2 mg/dL before day +21 and any two of the following: hepatomegaly, ascites, or weight gain (>5% from baseline) Reversal of portal venous flow on ultrasound (US) is characteristic but not part of diagnostic criteria. – Prophylaxis may include ursodiol and/or defibrotide. – Treatment Defibrotide: porcine intestinal mucosal oligonucleotide; anticoagulant with effects on endothelial cells, platelets, and fibrinolysis Supportive care: restriction of sodium and fluid intake; diuresis to keep fluid balance even (spironolactone if able to take PO) – Complications of VOD include renal insufficiency, altered mental status, cardiac failure, and bleeding. Thrombotic microangiopathy – Generalized endothelial dysfunction with microangiopathy – Calcineurin GVHD prophylaxis is a risk factor (CSA > tacrolimus). Combination with sirolimus

triples the risk from 4.2% to 10.8%. – Common symptoms: RBC fragmentation, thrombocytopenia with increased need for frequent platelet transfusions, elevated LDH, proteinuria, hypertension, elevation in creatinine, neurologic dysfunction – Treatment: Discontinue calcineurin inhibitors; supportive care; limited data for plasmapheresis, eculizumab (anti-C5 monoclonal antibody), and defibrotide Engraftment syndrome – Cytokine-mediated inflammation due to increasing neutrophil activity – Usually occurs by day +28 (earlier for autos, later for cord blood transplants) – Characterized by rash, fever, and pulmonary edema at the time of engraftment or before neutrophil recovery – Treatment: Rule out infection and then methylprednisolone for 3 to 7 days. Acute lung injury – Complication of TBI, chemotherapy (busulfan, cyclophosphamide), or infection (fungal, CMV); idiopathic pneumonia syndrome (IPS) if no etiology is found – Diagnosis: Cough, dyspnea, hypoxemia, fever CXR/CT: diffuse versus focal consolidations, nodules or cavitary lesions suggestive of fungus BAL: sensitive for CMV, RSV, PCP, other respiratory viruses; less sensitive for fungus – Treatment: early empiric broad-spectrum antibiotics and antifungals, respiratory support. Consider corticosteroids or TNF blockade for IPS. GVHD – See GVHD chapter

ADDITIONAL READING Chow E, Anderson L, Baker KS, et al. Late effects surveillance recommendations among survivors of childhood hematopoietic cell transplantation: a children’s oncology group report. Biol Blood Marrow Transplant. 2016;22(5):782–795. Fisher BT, Alexander S, Dvorak CC, et al. Epidemiology and potential preventative measures for viral infections in children with malignancy and those undergoing hematopoietic cell transplantation. Pediatr Blood Cancer. 2012;59(1):11–15. Pai SY, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371(5):434–446. Spellman SR, Eapen M, Logan BR, et al; for National Marrow Donor Program; Center for International Blood and Marrow Transplant Research. A perspective on the selection of unrelated donors and cord blood units for transplantation. Blood. 2012;120(2):259–265.

CODES ICD10 Z94.81 Bone marrow transplant status Z94.84 Stem cells transplant status

Z52.3 Bone marrow donor

FAQ Q: Should friends and family of a patient needing a transplant be tested as a potential match? A: If family contacts are willing to donate for an unrelated patient in need of a stem cell transplant, they should join the National Marrow Donor Program (NMDP) registry. However, extended family members are not likely to be a match for a related patient. Q: Can transplant recipients meet their donors? A: The NMDP has guidelines for donor/recipient contact. If both parties agree, contact is allowed 1 to 2 years after the transplant.

BOTULISM AND INFANT BOTULISM Jessica M. Khouri, MD Stephen S. Arnon, MD, MPH

BASICS DESCRIPTION An acute illness caused by neurotoxins produced by Clostridium botulinum or related neurotoxigenic species, which results in cranial nerve palsies and a symmetric, descending, flaccid paralysis The neurotoxin may be elaborated either in the large intestine of individuals temporarily colonized with the bacterium, or ingested, or absorbed from infected wounds. There are three main forms of the disease: – Infant botulism (IB) is the intestinal toxemia form in which swallowed spores germinate and colonize the infant’s colon and elaborate toxin in situ. – Foodborne botulism in children and adults occurs when preformed toxin is ingested with improperly prepared or stored foods. – Wound botulism occurs when spores of the bacterium contaminate the wound, germinate, and produce toxin that is then absorbed. EPIDEMIOLOGY IB is the most common form of human botulism in the United States. IB occurs in the 1st year of life, with ~90% of cases reported in the first 6 months of life. IB affects infants of all racial backgrounds and socioeconomic groups. Male to female ratio is 1:1. Toxin types A and B represent 98.5% of cases in United States (1976 to 2015), with dual toxin types (e.g., Ba, Bf) and more rare type E and type F comprising the remaining 1.5%. IB has been recognized in all 50 states, with a greater proportion of toxin type B cases east of the Mississippi River and toxin type A cases west of the Mississippi. Recognized on five of the six inhabited continents, Africa being the exception. Often, a history of a recent change in feeding practice is found. Honey is an identified food reservoir of C. botulinum spores. Honey consumption in U.S. IB patients from 1976 to 2015 was only approximately 4.8%. For the majority of IB cases, spore acquisition likely occurs from the natural environment, that is, infants inhale and then swallow spores attached to airborne microscopic dust particles. Nearby soil disruption may play a role. Breastfed infants who acquire IB tend to be older at onset than are formula-fed infants. Foodborne cases are usually associated with home-processed, low acid foods—especially vegetables, fruits, and condiments. Restaurant-associated outbreaks have occurred. Recent outbreaks in U.S. prisons have been associated with fermented alcoholic beverage commonly referred to as pruno. Wound botulism has been associated with “black tar” heroin injection drug use and traumatic injuries in teenagers.

Incidence U.S. IB incidence: 2.2 cases per 100,000 live births (1976 to 2014). The states with the highest incidence in descending order include Delaware, Utah, Hawaii, Pennsylvania, and California. Approximately 100 to 150 IB cases annually in United States Since the disease was first recognized >40 years ago, >4,400 cases of IB have been reported worldwide, of which >3500 are U.S. cases (~80%). Foodborne cases occur sporadically yet may result from a common exposure. Wound botulism is very rare. RISK FACTORS Infants who have 4 months of age – Recurrent episodes, particularly with a diurnal or late afternoon/evening pattern, are more likely due to colic. Question: Feeding? Significance: – Crying shortly after feeding suggests aerophagia or gastroesophageal reflux; 1 hour after feeding suggests formula intolerance. A rare cause of postprandial crying is anomalous coronary arteries. – Overfeeding or underfeeding, excessive air swallowing, inadequate burping, and improper formula preparation may contribute to excessive crying. Question: Fever? Significance: indicates potential need for evaluation of sepsis, meningitis, other infections

Question: Paradoxically increased crying (attempts at consolation make the crying worse, especially with lifting, rocking)? Significance: can be seen in meningitis, peritonitis, long bone fractures, arthritis Question: Stridor? Significance: implies possible upper airway obstruction (mechanical, functional) Question: Expiratory grunting? Significance: indicates higher likelihood of a significant pathologic cause of crying (especially cardiac, respiratory, and/or infectious disease) Question: Cold symptoms and/or day care attendance? Significance: increases likelihood of otitis media Question: Vomiting? Significance: increases likelihood of pathologic GI cause (e.g., pyloric stenosis, obstruction, gastroesophageal reflux with possible esophagitis), particularly in infant 10 point split between their verbal and performance IQ, and thus, the full-scale IQ may not reflect the true functional potential. Over development in childhood, the IQ tends to decline. Most patients have particular difficulties in the areas of arithmetic, auditory working memory, and executive functioning such as social judgment. Cognitive remediation should be tailored to the individual’s relative strengths and weaknesses. Q: How often are 22q11.2 deletions found in the general (unaffected) population? A: The penetrance of any individual associated clinical feature, when considering the multisystem nature of 22q11.2DS, is very high, approaching 100%. The typical 22q11.2 deletion is almost never found in control populations.

DENGUE VIRUS David M. Vu, MD A. Desiree LaBeaud, MD, MS

BASICS DESCRIPTION Dengue virus (DENV) is an arthropod-borne virus (arbovirus) that causes a febrile illness characterized by intense headache (classically retro-orbital), rash, abdominal pain, nausea, and joint pain. The majority of DENV infections is subclinical or asymptomatic, but some people with DENV infection develop severe dengue disease, which: – Manifests when the fever from the initial illness subsides – Is characterized by plasma leak leading to hypovolemic shock and death – Can be anticipated based on the presence of warning signs Identification of severe dengue-associated warning signs is important for determining need for additional monitoring and hydration. EPIDEMIOLOGY DENV has been reemerging over the last 50 years as a significant cause of febrile illness in tropical and subtropical areas of the world. Approximately 50 to 60 million symptomatic infections per year worldwide Estimated 300 million infections per year worldwide, including subclinical or asymptomatic infections RISK FACTORS Travel to or residing in an area that is experiencing an outbreak of or is endemic for DENV. Exposure to Aedes spp. mosquitoes Previous DENV infection of a serotype that is different than the circulating serotype GENERAL PREVENTION Mosquito avoidance – Wear clothing that maximizes skin coverage. – Use insect repellants such as N,N-diethyl-meta-toluamide (DEET). Empty open containers of standing water. PATHOPHYSIOLOGY DENV has a tropism for monocytes, macrophages, and dendritic cells. After invading a cell, it hijacks the cellular machinery to produce more infectious virus. Massive activation of the host inflammatory response is thought to lead to severe dengue disease. DENV nonstructural protein 1 (NS1) also directly affects vascular endothelium leading to plasma leakage. ETIOLOGY DENV is transmitted by Aedes aegypti and Aedes albopictus mosquitoes.

Aedes mosquitoes are – Endemic in many tropical and subtropical areas of the world – Highly adapted to thrive in peri-urban settings, often entering homes and laying eggs in man-made containers – Able to lay eggs in as little as a tablespoon of water – Expanding their habitat range due to global warming DENV is endemic in many parts of South and Southeast Asia, Central and South America, and Australia. Humans are only known reservoir for DENV. DENV can be categorized into four serotypes. – One or more serotypes may be circulating in an area. – Infection from one serotype is thought to protect against reinfection from the same (homologous) serotype but does not provide durable protection against the other (heterologous) serotypes. – Antibodies produced against one serotype (during primary infection) can cross-react with a heterologous serotype (during secondary infection) and increase the risk for developing severe dengue disease via a mechanism called antibody-dependent enhancement of infection. Single-stranded RNA virus DENV is a member of the Flaviviridae family of viruses that includes yellow fever virus, Japanese encephalitis virus, Zika virus, hepatitis C virus. COMMONLY ASSOCIATED CONDITIONS Other tropical and subtropical infections, including other mosquito-borne infections such as malaria or other arboviruses

DIAGNOSIS HISTORY Travel to or residence in an area known to be endemic for DENV Febrile phase lasting 3 to 7 days with: – Headache, classically severe retro-orbital pain – Myalgias and arthralgias – Maculopapular to petechial rash – Mucosal bleeding from gums and nose (observed more frequently in adults) Critical phase lasting 2 to 3 days that: – Starts when fever subsides – Consists of a vascular leak syndrome resulting in hypoproteinemia, ascites, pleural effusions or hypovolemic shock – Is characterized by leukopenia and thrombocytopenia Recovery phase during which hemodynamic status stabilizes followed by diuresis of fluids administered during the critical phase. PHYSICAL EXAM

Mucosal bleeding from the nose or gums (more frequent in adults than children) Maculopetechial rash Abdominal tenderness Hepatosplenomegaly Tourniquet sign 1. Take the patient’s blood pressure (BP) and record it, for example, 100/70. 2. Inflate the cuff to a point midway between SBP and DBP and maintain for 5 minutes. (100 + 70) ÷ 2 = 85 mm Hg 3. Release pressure and wait 2 minutes. 4. Count petechiae below antecubital fossa. A positive test is 10 or more petechiae per 1 square inch. ALERT Risk for developing severe dengue disease is associated with the following warning signs: – Abdominal pain or tenderness – Persistent emesis – Volume overload (edema) – Mucosal bleeding – Lethargy or restlessness – Hepatomegaly – Hemoconcentration Children with dengue with warning signs require hospital admission for: – IV fluids – Possible transfusions – Monitoring of hematocrit, peripheral perfusion, urine output, blood glucose DIFFERENTIAL DIAGNOSIS Sepsis Meningitis Acute gastroenteritis Chikungunya infection Malaria infection Zika virus infection DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Rapid diagnostic point-of-care test to detect DENV NS1 and/or serum IgM antibodies against DENV (not available in the United States) Reverse-transcriptase PCR (RT-PCR) to detect DENV RNA in blood Serum antibodies against DENV can be measured by enzyme-linked immunosorbant assay (ELISA). Follow-Up Tests & Special Considerations Plaque reduction neutralization test (PRNT) is a more virus-specific test for antibody. Test Interpretation A blood sample positive by DENV RT-PCR is diagnostic of acute DENV infection.

Positive anti-DENV IgM suggests acute primary infection. – Because antibodies to other flaviviruses may cross-react in this assay, a DENV IgM-positive sample is confirmed by PRNT. Positive anti-DENV IgG during the febrile phase raises the concern for secondary DENV infection, which is associated with higher risk for developing severe DENV disease.

TREATMENT GENERAL MEASURES Identify any dengue warning signs: – Abdominal pain or tenderness – Persistent vomiting – Edema – Mucosal bleeding – Lethargy or restlessness – Hepatomegaly – Hemoconcentration Management is based on the World Health Organization (WHO) dengue classification Probable dengue – Criteria Live in or travel to a dengue endemic area Fever and at least two of the following: nausea, vomiting, rash, leukopenia, arthralgia, myalgia, and a positive tourniquet test – Management Outpatient management with daily monitoring Oral rehydration solution Acetaminophen for treatment of fever Do not use nonsteroidal anti-inflammatory agents Dengue without warning signs (dengue fever) – Criteria Laboratory-confirmed dengue Fever and at least two of the following: nausea, vomiting, rash, leukopenia, arthralgia, myalgia, and a positive tourniquet test – Management Hospital admission of infants, consider outpatient management with daily monitoring in children >1 year Oral rehydration solution if tolerated Closely monitor temperature pattern, fluid balance, urine output, warning signs, hematocrit, white blood cell and platelet counts Dengue with warning signs (dengue hemorrhagic fever) – Criteria

Laboratory-confirmed dengue Fever and at least two of the following: nausea, vomiting, rash, leukopenia, arthralgia, myalgia, and a positive tourniquet test Any of the following warning signs: abdominal pain or tenderness, persistent emesis, volume overload (edema), mucosal bleeding, lethargy or restlessness, hepatomegaly, hemoconcentration – Management Intravenous crystalloid solutions Blood transfusions if necessary Monitor hematocrit, vital signs, peripheral perfusion, urine output, blood glucose and other organ functions. Severe dengue (dengue shock syndrome) – Criteria Laboratory-confirmed dengue One of the following: shock, significant volume overload with respiratory distress, severe clinical bleeding, organ failure – Management Intensive care treatment Intravenous crystalloid or colloid solutions Blood transfusion with fresh-packed red cells or fresh whole blood Platelet concentrates in case of massive bleeding MEDICATION First Line Maintain hydration. Oral rehydration for dengue without warning signs IV hydration for dengue with warning signs or for infants 6 months of age. Both HIV RNA and DNA PCR have sensitivities and specificities >95% after 2 weeks of age. By 1 month of age, 95% of HIV-infected infants will have positive HIV DNA PCR. Residual maternal antibodies may be detected up to 24 months. For those >2 years of age – HIV-1/HIV-2 antigen/antibody combination qualitative immunoassay simultaneously detects presence of HIV p24 antigen and HIV-1/HIV-2 antibodies. p24 antigen component allows for detection 2 to 3 weeks after infection and can help identify patients with acute HIV infection. CD4 counts – Obtained at diagnosis and routinely – Results need to be evaluated based on age-adjusted normal values. Absolute CD4 counts are elevated in childhood, with normal median values >3,000/mm3 in the 1st year of life, which then gradually decline with age, reaching values comparable with adult levels (800 to 1,000/mm3) by age 7 years. – For children 100,000 are associated with poor short-term (2 to 5 years) outcomes. – Also used as a marker of efficacy of treatment; goal is to suppress viral replication to the undetectable range for as long as possible. – Test is done at time of diagnosis to establish baseline and routinely to assess treatment adherence/efficacy. Other frequent lab abnormalities include thrombocytopenia, anemia, and elevated liver enzymes. ALERT Failure to screen for HIV infection during pregnancy results in inability to offer ART during pregnancy, which may lead to failure of preventing infant infection, as well as the inability to prescribe Pneumocystis jiroveci pneumonia prophylaxis to infected newborns.

TREATMENT GENERAL MEASURES Active immunizations – All infected children receive standard childhood immunizations, including the pneumococcal conjugate vaccine. – Infected children should receive yearly influenza A/B immunizations and 23-valent pneumococcal vaccine at age 2 years.

– Symptomatic children should not receive the varicella vaccine, and those with severely low CD4 counts should not receive measles-mumps-rubella vaccination. Prophylaxis: One of the major advances has been the ability to offer prophylaxis against the most common opportunistic infections. – Prophylaxis against Pneumocystis pneumonia with TMP-SMX is indicated for all HIV-infected infants between 4 to 6 weeks and 12 months of age, for those 1 to 6 years of age with CD4 count 21 years of age if they have HIV, solid-organ transplantation, or chronic immunosuppression. PROGNOSIS Therapy will not eradicate the virus; thus, HPV causes recurrent disease.

ADDITIONAL READING American Academy of Pediatrics. Human papillomaviruses. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:576–583. Gunter J. Genital and perianal warts: new treatment opportunities for human papillomavirus infection. Am J Obstet Gynecol. 2003;189(Suppl 3):S3–S11. Hathaway JK. HPV: diagnosis, prevention, and treatment. Clin Obstet Gynecol. 2012;55(3):671–680. Markowitz LE, Dunne EF, Saraiya M, et al; for Centers for Disease Control and Prevention. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-05):1–30. Workowski KA, Bolan GA; for Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1–137.

CODES ICD10 A63.0 Anogenital (venereal) warts

FAQ Q: What treatment is indicated during pregnancy? A: Most experts recommend surgical removal if necessary. Podophyllin is absolutely contraindicated. Q: Should partners of patients with genital warts be referred for examination? A: Recurrence is due to reactivation of the virus; reinfection plays no role. Partner may benefit from an examination to evaluate for the presence of warts and for education and counseling. There is no information regarding prophylaxis to prevent infection, so treatment for this is not indicated. Most partners have subclinical infection. Female partners should follow the routine recommendations for Pap smear screening.

Q: Are genital warts in children always indicative of sexual abuse? A: No. The HPV virus has an incubation period of many months. Thus, warts transmitted to infants at the time of birth may not become clinically apparent for 1 to 2 years. Whether the incubation period can be longer than this time period remains unknown. Thus, maternal history and, potentially, examination are both important factors. However, all children with anogenital warts should be evaluated by a clinician experienced in child abuse evaluations. It is possible that caregivers may transmit the virus to children through close but nonsexual contact; thus, this history is also important in older children. Q: Will young women still need to get Pap smears if they have received the HPV vaccine? A: Yes. The vaccine does offer good protection against the strains most commonly associated with genital warts and cervical cancer, 6, 11, 16, and 18. However, these strains are not the only ones that can cause infection or lead to cervical cancer. It is important to continue regular screening to ensure that one has not been exposed to other strains that may cause cervical dysplasia.

HYDROCELE Adam B. Hittelman, MD, PhD, FACS

BASICS DESCRIPTION A hydrocele is the accumulation of fluids around the testicle, within the tunica vaginalis or processus vaginalis. Communicating hydrocele: fluid passing from peritoneal cavity into patent processus vaginalis Noncommunicating hydrocele: fluid confined within the processus vaginalis (hydrocele of the cord) or tunica vaginalis Abdominal-scrotal hydrocele: fluid collection within processus vaginalis, extending into retroperitoneum Reactive hydrocele (noncommunicating): accumulation of fluid within tunica vaginalis caused by infection, trauma, or other inflammatory conditions EPIDEMIOLOGY 2–5% of male neonates have hydrocele. Male more common than female – Female: “cyst” or “hydrocele” in the canal of Nuck; may be communicating or noncommunicating Right more common than left Majority asymptomatic Simple (noncommunicating): commonly seen at birth, frequently bilateral, may be large – Majority spontaneously resolve in 12 to 24 months. Persistent hydroceles beyond 24 months and those presenting after birth more likely to be communicating Age >12 years old: majority noncommunicating Adolescent/adult hydroceles are generally acquired (reactive) and idiopathic in origin. RISK FACTORS Similar to inguinal hernia Prematurity, low birth weight, gestational progestin use, connective tissue anomalies, cystic fibrosis, cryptorchidism, posterior urethral valves, and other syndromic disorders Trauma or infection Lymphatic obstruction (i.e., varicocelectomy, filariasis, pelvic radiation, malignancy) PATHOPHYSIOLOGY Communicating hydrocele can become indirect inguinal hernia, with potential for incarceration. Noncommunicating hydrocele generally thought to be low clinical concern. Potential damage in large, tense hydroceles – Raised intrascrotal temperature can cause potential testicular harm. – Tense hydrocele may cause pressure atrophy.

– Increased resistive index observed in subcapsular artery and absent testicular diastolic flow indicate risk for permanent damage. ETIOLOGY Communicating hydrocele similar to indirect inguinal hernia (defined by contents entering through patent processus vaginalis: peritoneal fluid versus fat or visceral organ) In testicular descent, lip of peritoneum descends with testicle, the processus vaginalis, and covers testicle, tunica vaginalis. Patent processus in girls (canal of Nuck) related to descent of round ligament to labia, female equivalent of gubernaculum Related to delayed closure of processus vaginalis – Complete closure on both side in 18% of newborns – 40% close in first 2 months of life – 60% close by 2 years – Patent processus vaginalis commonly associated with undescended testicles – Adult autopsy data demonstrate 15–30% patent. Reactive (acquired) hydrocele is imbalance between fluid production and absorption. – Majority are idiopathic. Defective lymphatic drainage Aspirated fluid similar protein content to lymphatic fluid – Result of inflammation from trauma, testicular torsion, torsion of testicular appendage, epididymoorchitis – Postvaricocelectomy second most common cause

DIAGNOSIS HISTORY Inguinal or scrotal/labial swelling Age of onset – Birth, after birth, >12 years old Laterality Fluctuation in size: smaller in morning and larger over day in response to activity and upright position; change with crying/straining – May be preceded by constipation, upper respiratory infection, vomiting Undescended testicle Infection, trauma, torsion Pain/discomfort History of varicocele or other inguinal surgery PHYSICAL EXAM Palpate scrotal/labial swelling. Soft or tense

Compressible/reducible Palpate testicle. – Confirm descent. – Rule out mass, trauma, infection. Bowel contents—rule out hernia. Transillumination of scrotum to confirm fluid; not diagnostic DIFFERENTIAL DIAGNOSIS Indirect hernia Varicocele Spermatocele/epididymal cyst Epididymo-orchitis Hematocele Scrotal lymphedema Nephrotic syndrome DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Urine analysis and culture if concerns for epididymo-orchitis Tumor markers (hCG, α-fetoprotein [AFP]) if concern for testicular mass Imaging not required in an uncomplicated scrotal hydrocele with palpable testicle Transscrotal ultrasound if testicle difficult to palpate or concerns for concomitant problem – Assess testicle for pathology, blood flow, and inflammation/infection. – Differentiate bowel loops (hernia) from fluid. – Fluid tracking to peritoneal cavity can differentiate communicating versus noncommunicating. – Fluid tracking to abdominal component (retroperitoneal collection) demonstrates abdominoscrotal hydrocele. ALERT If palpation of testicle is limited by tense hydrocele, transscrotal ultrasound is important to assess for testicular location, viability, and potential pathology.

TREATMENT GENERAL MEASURES Conservative management for babies presenting at birth with noncommunicating hydrocele (no fluctuation in size) for 24 months – Consider surgical intervention if persistent >24 months. – Fluid aspiration discouraged in babies due to risk of infection Initial conservative management of infantile communicating hydrocele – Some surgeons advocate observation up to 12 to 18 months for potential spontaneous resolution. 84–89% spontaneous resolution (most by 6 months; none after 18 months) No difference in resolution rates between preterm versus term babies – Surgical intervention for development of inguinal hernia (7% of infantile hydroceles)

Treatment for communicating hydrocele presenting in children >1 year old is essentially same as for inguinal hernia. Reactive hydrocele managed conservatively – Antibiotics for epididymo-orchitis – Surgery reserved for pain or patients self-conscious regarding size/appearance SURGERY/OTHER PROCEDURES Inguinal approach for communicating hydrocele – Concomitant orchiopexy (undescended testicle) or orchiectomy (testis mass) when clinically indicated Controversial whether to explore or assess contralateral side with laparoscope for patent processus vaginalis – Visualization of a contralateral processus vaginalis (internal ring) does not always correlate with metachronous development of a contralateral inguinal hernia or communicating hydrocele. Transscrotal approach for reactive hydroceles in adolescent (>12 years old) and adult – Consider surgical intervention if persistent >24 months or very large. Transscrotal aspiration, with or without sclerosing agent, reserved for postoperative hydroceles

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Serial physical exam (q4–6mo in babies; annual for adolescent) for nonoperative management – Consideration of ultrasound for very tense hydrocele, preventing palpation of testicle Postoperative visit within weeks of surgery and subsequent visit to confirm healthy testicle, free of recurrent hydrocele

ADDITIONAL READING Cimador M, Castagnetti M, De Grazia E. Management of hydrocele in adolescent patients. Nat Rev Urol. 2010;7(7):379–385. Clarke S. Pediatric inguinal hernia and hydrocele: an evidence-based review in the era of minimal access surgery. J Laparoendosc Adv Surg Tech A. 2010;20(3):305–309. Hall NJ, Ron O, Eaton S, et al. Surgery for hydrocele in children—an avoidable excess? J Pediatr Surg. 2011;46(12):2401–2405. Koski ME, Makari JH, Adams MC, et al. Infant communicating hydroceles—do they need immediate repair or might some clinically resolve? J Pediatr Surg. 2010;45(3):590–593. Merriman LS, Herrel L, Kirsch AJ. Inguinal and genital anomalies. Pediatr Clin North Am. 2012;59(4):769–781. Naji H, Ingolfsson I, Isacson D, et al. Decision making in the management of hydroceles in infants and children. Eur J Pediatr. 2012;171(5):807–810. Osifo OD, Osaigbovo EO. Congenital hydrocele: prevalence and outcome among male children who underwent neonatal circumcision in Benin City, Nigeria. J Pediatr Urol. 2008;4(3):178–182.

CODES ICD10 N43.3 Hydrocele, unspecified N43.2 Other hydrocele P83.5 Congenital hydrocele

FAQ Q: Do hydroceles need to be corrected? A: Noncommunicating hydroceles can be managed conservatively and commonly will resolve within the first 12 to 24 months of life. Watchful waiting is recommended in this age group. Persistent hydroceles after age 2 years are assumed to be communicating hydroceles. Communicating hydroceles are managed similarly to indirect inguinal hernias. Some surgeons advocate monitoring asymptomatic communicating hydrocele for 6 to 12 months to see if they resolve. Hydroceles progressing to inguinal hernia require surgical intervention. Reactive hydroceles are treated if patient is symptomatic, selfconscious of size, or testicle is difficult to palpate. Q: What are the potential consequences of leaving hydrocele untreated? A: There are no clear long-term adverse consequences on fertility for leaving a noncommunicating hydrocele untreated. Potential concerns raised for testicular growth and function, though, may be alleviated with hydrocele repair. However, hydroceles may continue to grow in size, causing discomfort and distress. Untreated communicating hydrocele may progress to inguinal hernia. Q: Are there risks of a hydrocele developing on the other side? A: Similar to inguinal hernia, communicating hydroceles have risk of metachronous development of hydrocele on contralateral side. Inguinal hernia will present on other side 8.5–15% of time, although this rate is not clearly defined in communicating hydrocele. Visualization of a contralateral patent processus vaginalis does not always correlate with metachronous development of a contralateral inguinal hernia or communicating hydrocele. Q: What are the risks of hydrocele repair? A: Risks of the surgery are similar to inguinal hernia repair and include anesthetic risks, injury to testicle or spermatic cord structures (gonadal vessels, vas deferens), injury to ilioinguinal nerve, subsequent atrophy of the testicle, and recurrent hydrocele.

HYDROCEPHALUS Rebecca A. Dorner, MD Shenandoah Robinson, MD Vera Joanna Burton, MD, PhD

BASICS DESCRIPTION Active distension of the ventricular system resulting from inadequate passage of cerebral spinal fluid (CSF) from its point of production to point of absorption CSF compartment progressively enlarged at the expense of brain and/or spinal tissue EPIDEMIOLOGY Pediatric prevalence estimated at 1:1,000 children RISK FACTORS Intraventricular hemorrhage (IVH) Maternal medications (isotretinoin) Megalencephaly VACTERL association Genetics X-linked mutation in L1CAM gene most common genetic cause, accounting for 10% males with idiopathic isolated hydrocephalus, may also be associated with congenital muscular dystrophies/neuronal migrational defects (Walker-Warburg and muscle-eye-brain phenotypes) PATHOPHYSIOLOGY CSF originates from choroid plexus and interstitial fluid of brain/spinal cord and travels via both unidirectional bulk flow and pulsatile flow from cardiac cycle; starts in lateral ventricles → foramina of Monro → 3rd ventricle → aqueduct of Sylvius → 4th ventricle → foramina of Luschka and Magendie → subarachnoid space → into either arachnoid villi to venous system or to lymphatic sinuses Hydrocephalus results from obstruction to flow, impaired reabsorption, or rarely overproduction of CSF. Obstructive hydrocephalus: Blockage of flow or impaired absorption can necessitate urgent evaluation. – Acute (hours) (i.e., direct ventricular obstruction) → surgical emergency – Subacute/progressive (weeks to months) → increased ventricle size/interstitial edema = if not treated can cause brain herniation/arrest – Chronic (years) (i.e., late-onset aqueductal stenosis) → ventricles and skull slowly increase in size = slow loss of brain volume Communicating hydrocephalus—no morphologic obstruction to CSF, less time sensitive – May be secondary to arachnoid pathology or impaired elasticity of spinal dura ETIOLOGY Hydrocephalus is a heterogeneous condition with varying classification systems, organized here as “congenital,” present at birth, or “acquired,” occurring after birth, although some conditions may fit into

both groups. Congenital hydrocephalus – Aqueductal stenosis—most common cause of congenital hydrocephalus (~10% cases); stenosis of aqueduct of Sylvius (passageway between 3rd and 4th ventricles) – Neural tube defect–associated—that is, myelomeningoceles and Chiari II malformation (cerebellum and brainstem extend into foramen magnum) – Arachnoid cysts—most often located in posterior fossa, 3rd ventricle/suprasellar – Dandy-Walker malformation—4th ventricle enlarged/cystic as either outlet obstruction or failure of cerebellar development – Craniosynostosis/skeletal dysplasias—that is, achondroplasia, FGF mutations – Other associated syndromes—that is, trisomies 13, 18, 21, mucopolysaccharidoses (type II [Hunter], type VI [Maroteaux-Lamy]), Apert and Crouzon syndromes, NF1 Acquired – IVH—most in setting of prematurity. Posthemorrhagic hydrocephalus develops secondary to meningeal adhesions, clots, and granular ependymitis in 35% of all neonates surviving IVH; worse prognosis when associated with moderate/severe ventriculomegaly, echolucencies, or white matter injury – Infection (meningitis) can lead to leptomeningeal adhesions and granulations that block reabsorption of CSF (high-risk infections include enterovirus, CMV, lymphocytic choriomeningitis virus [LCMV], toxoplasmosis; may also occur intrauterine). – Brain tumors—in children, most often posterior fossa tumors compressing 4th ventricle – Head injury—blood from ruptured vessels may cause inflammation, scarring of meninges, or clot.

DIAGNOSIS PHYSICAL EXAM Prenatally diagnosed – Hydrocephalus may be diagnosed on prenatal ultrasound; when encountered on ultrasound subsequent fetal MRI can help to identify additional brain/spinal cord pathology. – Genetic testing via amniocentesis may be performed. Infants/children 2 cm/week), macrocephaly (OFC >2 SDs above mean for age, sex, gestational age), increased splaying of cranial sutures, frontal bossing, full/tense fontanelle with dilated scalp veins, paralysis of upward gaze or setting sun sign, lateral gaze palsy, nystagmus, ptosis, impaired pupillary response, lower extremity spasticity – ROS: worsening of apnea/bradycardia, lethargy/excessive fussiness, feeding intolerance – Cushing triad (hypertension, reflex bradycardia, respiratory irregularities) not generally seen in infants prior to fusion of cranial sutures Older children >2 years – Exam: papilledema (although may not be present in chronic hydrocephalus), new-onset diplopia or extraocular movement abnormality, (especially CN VI palsy), strabismus, spasticity of lower > upper

extremities, gait ataxia, hypothalamic-pituitary dysfunction from compression of hypothalamus/pituitary stalk by 3rd ventricle → diabetes insipidus, obesity, hypothyroidism, etc. – ROS: can have symptoms of increased intracranial pressure (ICP) (early-morning headache, vomiting, double vision, somnolence, behavioral changes) or focal deficits prior to changes in head size DIFFERENTIAL DIAGNOSIS Other causes of macrocephaly: Chronic subdural hematomas secondary to abusive head trauma “Benign” enlargement of subarachnoid spaces— enlargement of subarachnoid space with normal ventricles Familial megalencephaly Metabolic conditions (i.e., glutaric aciduria type 1) resulting in enlargement of subarachnoid spaces Pericerebral effusions Congenital anomalies of intracerebral or extracerebral veins (including AVMs) Tumors, intracranial cysts Head-sparing intrauterine growth retardation (relative macrocephaly) Rapid catch-up growth following prolonged malnutrition Variety of other causes: fragile X, autism spectrum disorders, Cowden syndrome, leukodystrophies (Alexander disease, Canavan disease, megalencephalic leukoencephalopathy), lysosomal storage disorders (Tay-Sachs, mucopolysaccharidoses, and gangliosidoses), organic acid disorders DIAGNOSTIC TESTS & INTERPRETATION Prenatal anatomy ultrasound and fetal MRI – Fetal MRI has superior soft tissue resolution versus ultrasound; can better study maturational, migrational, myelinating processes in high-resolution, ultrafast, single-shot T2-weighted sequences; compared with ultrasound, more sensitive evaluation of the fetal cortex, gray, and white matter structures – Fetal MRI does not reach the high sensitivity and specificity that postnatal MRI offers. Postnatal head ultrasound – Standard screening test for premature infants and neonates with suspected hydrocephalus or IVH – Anterior fontanelle must be patent. – Demonstrates ventricular size, presence of blood, echolucencies, and additional brain anomalies MRI – Standard MRI is definitive test in hydrocephalus to describe brain anatomy and white matter injury; should be first choice for elective studies – Rapid brain MRI protocols (i.e., FIESTA/HASTE/ultrafast sequences) for urgent shunt obstruction evaluation are replacing CT at some institutions; 2 cm/week, needs a head ultrasound. Preterm infants below a certain gestational age or birth weight (varies from hospital to hospital) should receive screening head ultrasounds while in the NICU. Q: What is the workup for shunt obstruction and shunt infection? A: Signs and symptoms of increased ICP should lead to an urgent neurosurgical evaluation; the most useful studies to evaluate obstruction include preferably MRI (rapid MRI if available, head CT if no MRI available) +/− shunt series. Fever is the most important indication for a shunt infection evaluation (shunt tap with CSF cell count, protein, glucose, Gram stain, and culture). Vigilance and caution

warranted as shunt infection may present similarly to other pediatric viral illnesses with low-grade fever, vomiting, etc. Q: Is hydrocephalus inherited? A: X-linked hydrocephalus associated with stenosis of the aqueduct of Sylvius is the most common heritable form, thought to account for 10% of males with isolated idiopathic hydrocephalus. Mutations in the L1CAM gene are the main genetic cause and often occur within abnormalities of the corpus callosum, hypoplasia or aplasia of the corticospinal tracts, adducted thumbs on exam. L1CAM testing should be strongly considered in all males with unexplained hydrocephalus but should be regarded as mandatory for those with a family history of hydrocephalus or adducted thumbs.

HYDRONEPHROSIS J. Christopher Austin, MD Michael C. Carr, MD, PhD

BASICS DESCRIPTION Hydronephrosis: dilation of the renal pelvis (pelviectasis) and calyces (caliectasis) due to excess urine in the collecting system of the kidney Hydroureteronephrosis: dilation of the renal collecting system and the ureter to the level of the bladder EPIDEMIOLOGY Incidence of hydronephrosis noted on routine prenatal ultrasound is 0.4–5%. 10–30% of fetuses with hydronephrosis are due to ureteropelvic junction obstruction. Posterior urethral valves and triad syndrome account for 1–2% of cases. ETIOLOGY Ureteropelvic junction obstruction – Partial obstruction at the region where the renal pelvis drains into the ureter Megaureter – Partial obstruction due to an intrinsic narrowing or an aperistaltic segment of distal ureter at the ureterovesical junction Vesicoureteral reflux – In primary reflux (grades I to V depending on the severity), it is due to an insufficient flap valve–type mechanism at the ureterovesical junction which allows urine to flow retrograde from the bladder up into the ureters. – Hydroureteronephrosis is usually seen only with higher grades of reflux (grades III to V) or secondary reflux (reflux in the presence of an abnormal bladder, in which the reflux is often due to high storage or voiding pressures within the bladder). Secondary reflux is not graded. Ureterocele – Hydroureteronephrosis secondary to obstruction of the ureter from a cystic dilation of the intravesical portion of the distal ureter – Most often associated with the upper pole ureter in duplicated collecting system; less frequently associated with a single system – Ureterocele is further classified as intravesical (contained completely within the bladder) or ectopic (extending down the bladder neck and often into the urethra). Ectopic ureter – A ureter that drains into an abnormal location outside of the bladder – The hydroureteronephrosis can be the upper pole ureter of a duplicated collecting system or a single system. – Ectopic ureters can drain at various sites along the lower urinary tract depending on the sex of the child. In boys, they can drain into the bladder neck, prostatic urethra, vas deferens, seminal vesicle,

or epididymis. In girls, they can drain into the bladder neck, urethra, introitus, and vagina. – The ectopic locations often require passage through the bladder neck or urogenital diaphragm, which produces obstruction of the distal ureter. Urolithiasis – Obstructing calculi often produce dilation of the urinary tract proximal to its location. – Stone disease is rare in infancy except in preterm infants who receive furosemide. – The hydronephrosis is usually associated with renal colic. Posterior urethral valves – Hydroureteronephrosis: nearly always bilateral, produced by outflow obstruction of the bladder from an obstructing membrane in the prostatic urethra – Because both kidneys are affected, there is a significant risk of chronic kidney disease and eventual progression to end-stage renal disease. Triad syndrome – Hydroureteronephrosis, often with massively dilated ureters and a large bladder – Also known as prune belly syndrome or Eagle-Barrett syndrome – These boys have a triad of hypoplastic abdominal wall musculature (leading to a prunelike appearance), bilateral undescended testes, and a dilated urinary tract. – May have associated urethral atresia, imparting worse renal function prognosis – Significant risk of renal insufficiency and bladder dysfunction in these patients

DIAGNOSIS HISTORY Newborns – Antenatal hydronephrosis: presence of hydronephrosis or hydroureteronephrosis – If unilateral, severity of hydronephrosis and the status of contralateral kidney – If bilateral, presence of bladder wall thickening, bladder enlargement, bladder emptying, or a dilated posterior urethra (keyhole sign) may indicate posterior urethral valves or triad syndrome. – If oligohydramnios is present, pulmonary hypoplasia is a concern. The presence of oligohydramnios, increased renal echogenicity, and cystic changes in the kidneys are indicators of poor renal function and dysplasia. Older children – History of urinary tract infections or gross hematuria – General health and growth (poor growth due to chronic kidney disease) – Daytime incontinence, poor urinary stream, or symptoms of voiding dysfunction may be an indicator of bladder dysfunction due to posterior urethral valves. – History of episodic abdominal (which may not lateralize well), flank, or back pain in the presence of hydronephrosis is often due to symptomatic ureteropelvic junction obstruction (see topic “Ureteropelvic Junction Obstruction”). PHYSICAL EXAM

Neonate – Signs of oligohydramnios (Potter facies, lateral patellar dimples, clubfeet, and other limb deformities) and respiratory distress – Palpable abdominal mass – Palpable walnut-sized bladder (posterior urethral valves) – Patent urachus – Ascites – Development of abdominal wall musculature (wrinkled prunelike appearance in triad syndrome) Older children – Presence of abdominal mass – Abdominal or flank tenderness DIFFERENTIAL DIAGNOSIS Cystic renal tumor – Most commonly Wilms tumor – Distinguished from hydronephrosis by ultrasound or CT scanning Multicystic dysplastic kidney – Can be difficult to distinguish from severe hydronephrosis with marked parenchymal thinning – Renal scan will show no function or perfusion with multicystic dysplastic kidney. DIAGNOSTIC TESTS & INTERPRETATION Newborn – Hydronephrosis or hydroureteronephrosis with a normal contralateral kidney does not require any immediate laboratory testing. – If both kidneys are affected or a solitary kidney is affected, there is a need for serial assessments of renal function (serum electrolytes and creatinine). Older children – Urinalysis to detect hematuria or pyuria; culture if infection suspected – In cases where both kidneys are affected or there is a solitary kidney, renal function should be evaluated. Infants with antenatally detected hydronephrosis may be evaluated with three imaging studies: – Renal/bladder ultrasound – Voiding cystourethrogram – Renal scan A recent consensus of pediatric radiologists, urologists, nephrologists, and perinatologists have developed a new classification for urinary tract dilation (UTD). – The UTD is classified base on the presence or absence of central versus peripheral calyceal dilation, normal or abnormal renal parenchyma, degree of dilation of the renal pelvis, and associated abnormalities of the bladder and ureters. – They are reported for postnatal hydronephrosis as UTD—UTD P1 (low risk), UTD P2 (intermediate risk), and UTD P3 (high). – Follow-up studies, timing, and prophylactic antibiotic recommended based on the risk stratification

groups. This classification system is being adopted at many centers as it gives a uniform system for the classification of prenatal and postnatal hydronephrosis. The timing for evaluation can be elective for unilateral hydronephrosis with a normal contralateral kidney, but if both kidneys are affected or a solitary kidney is involved, prompt evaluation of the newborn should be undertaken. Renal/bladder ultrasound – Because of a period of relative oliguria of a newborn in the first 24 to 48 hours of life, an ultrasound may underestimate the degree of hydronephrosis during this time and thus should be postponed until the infant is at least 48 hours old and having good urine output. – This should not preclude evaluating an infant during this time as long as a normal study is repeated after 48 hours of life and 90% caused by hyperparathyroidism (HPT) or malignancy Children: more diverse etiologies dependent on age of presentation RISK FACTORS Family history of hypercalcemia Family history of renal stones Chronic renal failure Immobilization Certain genetic syndromes Certain malignancies History of neck irradiation Gestational maternal hypocalcemia PATHOPHYSIOLOGY Increased calcium influx from the intestinal tract or the skeleton Increased renal tubule calcium reabsorption ETIOLOGY ALERT The first step in the determination of an etiology of hypercalcemia is measurement of an intact serum parathyroid hormone (intact PTH) concentration. Hypercalcemia with increased PTH – Familial isolated primary HPT Autosomal dominant (AD) Parathyroid hyperplasia or adenoma(s) MEN1, HRPT2, HRPT3 mutations – Multiple endocrine neoplasia (MEN) MEN1 (AD) ■ MEN1-inactivating mutation ■ Parathyroid tumors in 90% ■ Pancreatic and pituitary tumors

MEN2A (AD) ■ RET proto-oncogene mutations ■ Parathyroid tumors in 20% ■ Medullary thyroid carcinoma and pheochromocytoma – Sporadic parathyroid adenoma Cyclin D1/PRAD1 MEN1 mutations – Parathyroid carcinoma (rare) – Hyperparathyroidism-jaw tumor syndrome (HPT-JT) HRPT2 inactivating mutations Parathyroid tumors may present in adolescence. Mandibular, maxillary, and renal tumors may occur. – Neonatal severe HPT (NSHPT) Homozygous inactivating calcium-sensing receptor (CaSR) mutations (AR) – Neonatal HPT (NHPT) Heterozygous inactivating CaSR mutations or dominant/negative (less severe presentation) Hypercalcemia with normal PTH – Familial benign hypercalcemia or familial hypocalciuric hypercalcemia (FHH) Heterozygous inactivating CaSR mutations (AD) Typically asymptomatic Mild hypercalcemia PTH is usually normal (slightly elevated in 15–20%). Fractional calcium excretion 14 mg/dL) – Nausea, vomiting – Dehydration – Encephalopathy – Psychological changes, – Poor feeding, hypotonia, and apnea (in newborns) PHYSICAL EXAM Usually normal—unless syndromic Parathyroid mass usually not palpable Hypertension Dehydration Soft tissue calcifications uncommon DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Confirm hypercalcemia and obtain intact PTH, serum phosphate, and magnesium, plus electrolyte panel. Collect urine to measure calcium excretion and evaluate calcium-to-creatinine ratio: – Normal spot urine calcium to creatinine varies by age (50,000/μL and consist of myeloid precursor cells in the peripheral blood at all stages of maturity rather than proliferation of an immature WBC clonal population characteristic of malignancies. – Infectious causes: Bordetella pertussis, Clostridium difficile, Shigella, EBV, CMV – Leukemoid reactions reflect a physiologic bone marrow response to cytokine secretion prompted by external stimuli such as infection or inflammation. – Nucleated RBCs (also seen in malignancy) DIAGNOSTIC TESTS & INTERPRETATION Initial Tests (screening, lab, imaging) Peripheral blood analysis with morphology and flow cytometry aid in immediate diagnosis of acute leukemia. ALERT Confirm presence of leukemic blasts. Automated counting machines may mistake leukemic blasts for atypical/reactive lymphocytes or even monocytes. Confirmation may require a manual differential and a pathologist or oncologist to review the peripheral smear. Evaluate other cell lines. Concurrent presence of anemia and/or thrombocytopenia supports an underlying marrow disorder and may require interventions such as transfusions. Tumor lysis syndrome (TLS): – Laboratory TLS: occurrence (within same 24-hour period) of two or more of three metabolic derangements (hyperkalemia, hyperphosphatemia, hyperuricemia) – Clinical TLS: presence of laboratory TLS plus one or more of the following: increased creatinine, cardiac arrhythmia, seizure, or death Obtain chest radiograph (CXR), even if asymptomatic. – Evaluate for mediastinal mass. – Evaluate for pulmonary infiltrates. If clinically indicated, obtain MRI or CT. Diagnostic Procedures/Other

Bone marrow aspirate may be required per clinical trial criteria, which includes cytogenetics for future prognostic/therapeutic decision making.

TREATMENT The goal of treatment is to quickly make a correct diagnosis and implement definitive therapy while simultaneously identifying and addressing the potential complications of leukostasis secondary to hyperleukocytosis. Leukoreduction refers to interventions that result in a rapid decline of the WBC. Leukoreduction is an absolute indication if a patient shows symptoms or signs of leukostasis. It is a relative indication in an asymptomatic patient with a WBC count ≥100,000 to 300,000/μL (depending on type of leukemia). Controversy exists about its impact on decreasing morbidity, risk of CNS hemorrhage, or mortality. Induction chemotherapy – This is the definitive therapy for hyperleukocytosis secondary to malignancy. – Initiate chemotherapy as soon as malignant diagnosis is confirmed. Management – Aggressive hydration at 2 to 4 times maintenance – Identify and correct metabolic abnormalities. TLS Hyperuricemia, indication for allopurinol or rasburicase – Identify and correct coagulopathies. – Transfuse for cytopenias. Do not transfuse packed RBCs if hemodynamically stable due to increased blood viscosity. Do not exceed hemoglobin 10 g/dL. Transfuse platelets to maintain platelets >10,000/μL; will not affect blood viscosity Cytoreduction – Leukapheresis Benefit: Each pheresis session decreases the circulating WBC count by 20–50%. During pheresis, FFP may be administered to reduce risk of hemorrhage. Limitation: availability of equipment, trained personnel, and anticoagulation Caution: Leukapheresis only transiently decreases blast counts until definitive treatment can be initiated. – Exchange transfusion, including partial Benefit: This technique is preferred over leukapheresis when (i) patient is an infant or 10 g/dL as increasing hematocrit increases blood viscosity. For thrombocytopenia, transfuse to maintain platelet >20,000/μL because platelet transfusions minimally increases blood viscosity. If CNS hemorrhage is present, maintain platelets at 75,000 to 100,000/μL.

HYPERLIPIDEMIA Zeina M. Nabhan, MD

BASICS DESCRIPTION Hyperlipidemia is an elevation of serum lipids. These lipids include cholesterol, cholesterol esters (compounds), phospholipids, and triglycerides. Lipids are transported as part of large molecules called lipoproteins. Five major families of lipoproteins: – Chylomicrons – Very-low-density lipoproteins (VLDLs) – Intermediate-density lipoproteins (IDLs) – Low-density lipoproteins (LDLs) – High-density lipoproteins (HDLs) Normal serum lipid concentrations: – Total cholesterol: 170 mg/dL (borderline, 170 to 199 mg/dL) – LDL cholesterol: 160 mg/dL and there is a family history of premature CVD (≤55 years of age for men, ≤65 for women) or ≥2 other risk factors are present (obesity, hypertension,

cigarette smoking). – Diabetes and LDL ≥130 mg/dL Physicians caring for overweight and obese children with lipid disorders should emphasize the importance of diet and exercise rather than drug therapy for most of their patients. Statins (1st-line drug therapy): decrease endogenous cholesterol synthesis and increase clearance of circulating LDL – Similar safety and efficacy in the treatment of lipid disorders in children as in adults – Side effects include hepatitis and myositis. Bile acid–binding resins: bind cholesterol in bile acids in intestine and prevent reuptake into enterohepatic circulation – Associated with GI discomfort – Very poor compliance in children Niacin: lowers LDL and triglycerides while increasing HDL; however, poorly tolerated in children due to side effects occurring in >50%, including flushing, itching, and elevated hepatic transaminases Drugs needing further pediatric studies: cholesterol absorption inhibitors and fibrates ADDITIONAL THERAPIES Activity: 60 minutes of moderate to vigorous play or physical activity daily Reduce sedentary behaviors (e.g., watching TV, playing videogames, using computers). Participation in organized sports

ONGOING CARE FOLLOW-UP RECOMMENDATIONS Patient Monitoring For patients with primary hyperlipidemia off medication, follow-up should be performed every 1 to 2 years with lipoprotein profile. For those patients on medication, follow-up should be conducted every 3 to 6 months. For all other patients with risk factors and normal lipid profile, a monitored lifestyle and diet changes should be strongly recommended at every office visit. DIET Dietary modification is safe in the treatment of hyperlipidemia in children >2 years of age: – Restrict saturated fat to 95th percentile, it should be repeated on two more occasions. If BP is >99th percentile plus 5 mm Hg, prompt referral for evaluation and therapy should be made. If the patient is symptomatic, immediate referral and treatment are indicated. Mild primary hypertension may be managed with nonpharmacologic treatment: weight reduction, exercise, sodium restriction, avoidance of certain medications such as pseudoephedrine. Pharmacologic therapy should be directed to the cause of secondary hypertension when this is known or for severe, sustained hypertension. Medications may be needed in children with mild to moderate hypertension if nonpharmacologic therapy has failed or if end-organ changes, kidney disease, or diabetes is present. MEDICATION Classes of antihypertensive agents include α- and β-blockers, diuretics, vasodilators (direct and calcium channel blockers), ACE inhibitors, and angiotensin receptor blockers (ARBs). Therapy should be initiated with a single drug. Avoid multiple medications with the same mechanism of action. Elicit a history of adverse effects and adjust medications accordingly. There are no trials with clinical significant outcomes to support a preferential class of antihypertensive medications in pediatric essential hypertension. Specific classes should be used with concurrent medical conditions: – ACE inhibitors or ARBs in children with diabetes and microalbuminuria or proteinuric renal diseases – β-blockers or calcium channel blockers with migraine headaches Certain classes of medication should be avoided in patients with specific conditions, such as: – Asthma and diabetes (β-blockers) – Bilateral renal artery stenosis (ACE inhibitors) ACE inhibitors are associated with congenital malformations and are contraindicated during pregnancy; calcium channel blockers and β-blockers are alternatives. ADDITIONAL THERAPIES For overweight adolescents, a DASH-type diet: 8 servings of fruits and vegetables, 3 servings of lowfat dairy, and 3 g of fat and >480 mg of sodium per serving) Regular aerobic physical activity (30 to 60 minutes at least 5 days a week) Limitation of sedentary activities to 2 inhs† 2×/day 1 inh† 2×/day

*It is preferable to use a higher mcg/puff or mcg/inhalation formulation to achive as low a number of puffs or inhalations as possible. †Abbreviations: DPI, dry power inhaler (requires deep, fast inhalation); inh, inhalation; MDI, metered dose inhaler (releases a puff of medication); neb, nebule. National Heart, Lung, and Blood Institute, National Institutes of Health. Asthma care quick reference: http://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf. Accessed March 1, 2015.

3–4 inhs† pm or 2 inhs† 2×/day 1 inh† 2×/day or 2 inhs† pm

≥3 inhs† 2×/day ≥3 inhs† divided in 2 doses

ECZEMA Table 15. Relative Potencies of Topical Corticosteroids Class I. Very high potency

II. High potency

III–IV. Medium potency

V. Lower-medium potency

VI. Low potency

VII. Lowest potency

Drug Augmented betamethasone dipropionate Clobetasol propionate Diflorasone diacetate Halobetasol propionate Amcinonide Augmented betamethasone dipropionate Betamethasone dipropionate Desoximetasone Desoximetasone Diflorasone diacetate Fluocinonide Halcinonide Mometasone furoate Triamcinolone acetonide Betamethasone valerate Clocortolone pivalate Desoximetasone Fluocinolone acetonide Flurandrenolide Fluticasone propionate Fluticasone propionate Mometasone furoate Triamcinolone acetonide Hydrocortisone butyrate Hydrocortisone probutate Hydrocortisone valerate Prednicarbate Alclometasone dipropionate Desonide Fluocinolone acetonide Dexamethasone Hydrocortisone Hydrocortisone acetate

Dosage form(s) Ointment Cream, foam, ointment Ointment Cream, ointment Cream, lotion, ointment Cream Cream, foam, ointment, solution Cream, ointment Gel Cream Cream, gel, ointment, solution Cream, ointment Ointment Cream, ointment Cream, foam, lotion, ointment Cream Cream Cream, ointment Cream, ointment Cream Ointment Cream Cream, ointment Cream, ointment, solution Cream Cream, ointment Cream Cream, ointment Cream, gel, foam, ointment Cream, solution Cream Cream, lotion, ointment, solution Cream, ointment

Strength (%) 0.05 0.05 0.05 0.05 0.1 0.05 0.05 0.25 0.05 0.05 0.05 0.1 0.1 0.5 0.1 0.1 0.05 0.025 0.05 0.05 0.005 0.1 0.1 0.1 0.1 0.2 0.1 0.05 0.05 0.01 0.1 0.25, 0.5, 1 0.5–1

From Paller AS, Mancini AJ. Eczematous eruptions in childhood. In: Paller AS, Mancini AJ, eds. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. St. Louis, MO: Elsevier; 2011: 49, with permission from Elsevier.

INDEX A Aagenaes syndrome, 532, 632 Aarskog syndrome, 1044 Abdominal mass, 2–3 Abdominal migraine, 4–5, 416 Abdominal pain, 6–7. See also specific conditions causing Abdominal wall defects, 514 Abnormal bleeding, 8–9 Abnormal uterine bleeding (AUB), 310–311 ABO isoimmunization, 426 Abruptio placentae, 304, 426, 626 Abscess. See also specific conditions causing appendiceal, 46 Bezold, 575 brain, 46, 47, 118–119, 851, 940 breast, 126–127 dental, 46, 274–275, 318, 319, 484, 485, 800 epidural, 46, 851 hepatic, 42–43, 436 horseshoe, 690 intersphincteric, 690 intra-abdominal, 693 ischiorectal, 690 lung, 717 lymph node, 561 neck, 575 omphalitis, 657 orbital, 851 perianal, 690 perirectal, 690–691 peritoneal, 46, 47 peritonsillar, 46, 318, 319, 622, 694–695, 863, 942 psoas, 789 retropharyngeal, 319, 622, 623, 694, 788–789 scalp, gonococcal, 400 subperiosteal, 851 supralevator, 690 tuboovarian, 169, 680

Abuse. See Child abuse Acanthosis nigricans, 250, 652, 653 Accommodation, visual, 772 Accommodative esotropia, 773, 882, 883 Acetaminophen poisoning, 10–11, 20–21, 897, 1067 Achondrogenesis type I, 1044 Achondroplasia, 460, 845, 1044 Acidosis. See Diabetic ketoacidosis; Metabolic acidosis Acne, 12–15, 604, 1064 Acquired immune deficiency syndrome (AIDS), 454–455. See also Human immunodeficiency virus (HIV) infection Acrocyanosis, 132 Acrodermatitis enteropathica, 82, 226, 294, 295, 1044 Actinic prurigo (AP), 706, 707 Actinomycosis, 46 Activated demonstration, 1028 Acute cerebellar ataxia (ACA), 78–79 Acute chest syndrome, 848, 849 Acute diarrhea, 188, 298 Acute disseminated encephalomyelitis (ADEM), 78, 326, 327, 958 Acute drug withdrawal, 16–17 crying in, 243 neonatal abstinence syndrome in, 16–17, 364, 626–627 opioid, 16–17, 626–627, 658, 659 Acute hemolytic transfusion reaction, 304, 948–949 Acute hemorrhagic leukoencephalitis, 326 Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 408 Acute intermittent porphyria, 1044 Acute interstitial nephritis (AIN), 18 Acute kidney injury (AKI), 18–19 in hemolytic uremic syndrome, 18, 428–429 in nephrotic syndrome, 637 in rhabdomyolysis, 18, 19, 792–793 in sepsis, 831 Acute liver failure (ALF), 10–11, 20–21 Acute lymphoblastic leukemia (ALL), 22–23, 147, 468 Acute motor axonal neuropathy, 408 Acute mountain sickness (AMS), 36–37 Acute myeloid leukemia (AML), 24–25, 147, 468, 548 Acute necrotic collection (ANC), 672 Acute necrotizing ulcerative gingivitis (ANUG), 390

Acute otitis media (AOM), 318, 319, 668–669 Acute pancreatitis, 674 Acute peripancreatic fluid collection (APFC), 672 Acute poststreptococcal glomerulonephritis (APSGN), 394–395, 422, 423, 509, 819 Acute promyelocytic leukemia, 24, 25 Acute pyelonephritis, 762, 763 Acute rheumatic fever (ARF), 796–797, 819 Acute scrotum, 336 Acute tubular necrosis (ATN), 18 Adapt model, for feedback, 1030 Addison disease, 478, 742–743 Adenomatous polyps, 728, 729 Adenosine deaminase deficiency, 840–841 Adenotonsillar hypertrophy, 852 Adenovirus infection, 26–27 cardiomyopathy in, 152 conjunctivitis in, 26–27, 222, 223 fever and petechiae in, 358 fever of unknown origin in, 361 hematuria in, 422, 423 hepatitis in, 1000 pharyngitis in, 702 sore throat in, 862 Adhesive atelectasis, 80 Adjustment disorder, 86, 278, 279 Adolescent acne, 12 Adolescent contraception, 231 Adolescent idiopathic scoliosis, 820–821 Adolescent substance use, 892–893 Adolescent suicide, 896–897 Adrenal crisis, 487, 743 Adrenalectomy, 251 Adrenal hyperplasia, congenital. See Congenital adrenal hyperplasia Adrenal hypoplasia congenita, 742 Adrenal insufficiency, 478 autoimmune, 743 cancer therapy and, 146 chronic, 743 primary, 742–743 Adrenal mass, 2–3 Adrenarche, premature, 736–737

Adrenocortical neoplasms, 250 Adrenocorticotropic hormone (ACTH) deficiency, 486–487 Adrenocorticotropic hormone (ACTH) unresponsiveness, 742–743 Adrenoleukodystrophy, 742–743, 1044 Aeromonas, 662 Agenesis of corpus callosum, 1044 Aggression, autism spectrum disorder and, 88, 89 Agoraphobia, 828 Aicardi syndrome, 510, 1044 AIDS, 454–455. See also Human immunodeficiency virus (HIV) infection Air leak syndrome, 696, 781 Air travel, ear pain in, 98–99, 318 Alagille syndrome, 192, 437, 532, 632, 633, 774, 924, 1044 Alarm therapy, for enuresis, 333 Albinism, 706, 707 Albright syndrome, 154 Albumin supplementation, 69 Albuminuria, 194 Alcohol abuse/use, 892, 893 Alcohol dependence, 893 Alcoholic liver disease, 196 Alcohol intoxication, 28–29 Alcohol-related birth defects (ARBD), 356–357 Alcohol-related neurodevelopmental disorder (ARND), 356–357 Alcohols, toxic, 936–937 Alcohol withdrawal, 16–17 Aldosterone resistance/deficiency, 776 Aldosteronism, 472, 480, 481 Alexander disease, 1044 “Alice in Wonderland syndrome,” 416 Alkali supplementation, for renal tubular acidosis, 777 Allergic angioedema, 30, 164, 438 Allergic bronchopulmonary aspergillosis (ABPA), 70–71 Allergic child, 30–31 Allergic colitis, 554 Allergic conjunctivitis, 30, 222, 223, 798 Allergic dermatitis, 110, 226, 227, 294, 748 Allergic fungal rhinosinusitis (AFRS), 70, 71 Allergic rhinitis. See Rhinitis, allergic Allergic rhinoconjunctivitis, 502 Allergy

asthma and, 74–77 food, 30–31, 48, 82, 366–367 latex, 31, 48, 637 sinusitis in, 850 Alloimmunization, 949 Alopecia, 32–33, 288, 556, 962 Alopecia areata, 32–33, 306, 492, 1044 α1-Antitrypsin (AAT) deficiency, 34–35, 1044 cholestasis in, 632, 633 cirrhosis in, 34, 35, 196 hepatitis in, 192 hepatomegaly in, 436, 437 jaundice in, 35, 532, 533 portal hypertension in, 34, 35, 730 α-thalassemia, 926–927 Alport syndrome, 154, 194, 394, 422, 423, 1044 Altitude illness, 36–37 Alveolar capillary dysplasia (ACD), 232, 696 Alzheimer disease, 307 Ambiguous genitalia, 38–39, 216, 217, 743, 746 Amblyopia, 40–41 cataract and, 40, 154, 155 glaucoma and, 392, 393 lacrimal duct obstruction and, 540–541 in NICU graduates, 364 refractive error and, 772, 773 with retinopathy of prematurity, 787 strabismus and, 882 Amebiasis, 42–43, 370–371 Amenorrhea, 44–45, 56, 57, 724 Ammonia. See Hyperammonemia Amniotic fluid, meconium-stained, 580 Amniotic fluid aspiration, 304 Amniotic fluid embolism, 304 Amniotic membrane transplant, 879 Amphetamine abuse/use, 892, 902 Amyand hernia, 514 Amyloidosis, 72, 238 Anaerobic infections, 46–47 Anal fissures, 225, 243, 555, 842 Anal stenosis, 224, 225

Analytic reasoning, 1031 Anaphylaxis, 30, 48–49, 982, 983 in factor IX infusion, 431 food-induced, 48, 366–367 IgE-mediated, 48 in insect bites or stings, 859 medication-induced, 48 in serum sickness, 837 in transfusion reaction, 948–949 Anaplasmosis, 324–325, 360, 361, 802–803 Anaplastic large cell lymphoma (ALCL), 646–647 Ancylostoma braziliense, 252 Ancylostoma caninum, 252 Ancylostoma duodenale, 66 Andersen disease, 1044, 1047 Androgenetic alopecia, 32 Androgen excess, 12, 44, 45, 216–217, 724–725 Androgen insensitivity, 38, 384, 754, 1044 Anemia. See also Hemolytic anemia; Iron deficiency anemia; Sickle cell disease; specific conditions causing aplastic, 60–61, 138, 340 of chronic disease (inflammation), 50–51, 195, 602 Fanconi, 22, 138, 545, 670, 1046 macrocytic, 584 megaloblastic, 584–585, 847 microcytic, 602–603, 926–927 pallor in, 670–671 pernicious, 492, 584 of prematurity, 365 Anencephaly, 638–639 Aneurysms disseminated intravascular hemorrhage with, 304 intracranial hemorrhage with, 522, 523 in Kawasaki disease, 536–537 in polycystic kidney disease, 722, 723 Angelman syndrome, 363, 372, 876, 1044 Angioedema, 322, 323, 982 allergic, 30, 164, 438 C1 esterase deficiency and, 212, 213, 322, 323, 338 complement deficiency and, 212 epiglottitis with, 338

food allergy and, 366 hereditary, 212, 327, 338, 438–439 idiopathic, 438 Angiofibroma, facial, 966, 967 Angiomyolipoma, 966, 967 Animal bites, 572–573, 766–767 Aniridia, 392, 1016 Anisometropia, 772 Anisometropic amblyopia, 40 Ankyloglossia, 52–53, 128, 129, 867 Ankylosing spondylitis, 96, 97, 872–873 Ankyrin deficiency, 440 Annular ligament displacement, 768–769 Annular pancreas, 518, 578 Anogenital warts, 1008 Anomalous left coronary artery from pulmonary artery (ALCAPA), 54–55 Anomalous pulmonary venous return, 220, 1041 Anorchia, 246, 247, 754 Anorectal atresia, 578 Anorexia nervosa, 56–57 hypokalemia in, 480, 481 rectal prolapse in, 770 weight loss in, 1010 Antalgic gait, 92 Anterior horn cell diseases, 868 Anthrax, 58–59 Anthrax vaccine absorbed (AVA), 58 Antibiotic(s) for acne, 13–14 for anaerobic infections, 47 for anaplasmosis, 325 for anthrax, 58, 59 for appendicitis, 63 for babesiosis, 95 for bacterial meningitis, 327, 359, 831 for bacterial vaginosis, 989 for biliary atresia, postoperative, 105 for blepharitis, 111 for brain abscess, 119 for breast abscess, 127 for bronchiolitis-associated infections, 135

for Campylobacter infection, 145 for cat-scratch disease, 157 for cavernous sinus syndrome, 159 for cellulitis, 165, 689 for cervicitis, 169, 989 for chancroid, 171 for chlamydia, 169, 181, 223, 843 for Chlamydophila pneumoniae infection, 183 for cholera, 187 for chronic granulomatous disease, 191 for common variable immunodeficiency, 210–211 for conjunctivitis, 223 for costochondritis, 234 for Crohn disease, 239 for Cyclospora infection, 257 for cystic fibrosis, 258–259 for dental infections, 274–275 for diaper rash, 294, 295 for diarrhea, 299 for diphtheria, 301 for ehrlichiosis, 325, 327 for endocarditis, 331 for epididymitis, 337 for epiglottitis, 339 for fever and petechiae, 359 for food poisoning, 371 for frostbite, 375 for gastritis, 381 for gastroesophageal reflux, 383 for gingivitis, 391 for glomerulonephritis, 395 for gonococcal infections, 169, 400, 401, 843 for group A β-hemolytic Streptococcus, 885 hematuria with, 422 hemolysis with, 424 for hemolytic uremic syndrome, 429 for hepatic encephalopathy, 21 for histiocytosis, 449 for impetigo, 509 intracranial hypertension with, 496 for intussusception, 525

for irritable bowel syndrome, 530 for lacrimal duct obstruction, 540 for lice, 551 liver toxicity with, 20 long QT syndrome with, 552 for Lyme disease, 95, 101, 559 for lymphadenitis, 561 for lymphedema, 563 for malaria, 568, 569 for mammalian bites, 573 for mastoiditis, 127, 575 for meconium aspiration syndrome, 581 for meningitis, 587 for meningococcemia, 589 for Mycoplasma encephalopathy, 327 for neck masses, 623 for nontuberculous mycobacterial infections, 649 for omphalitis, 657 for ophthalmia neonatorum, 223, 400 for osteomyelitis, 663 for otitis externa, 667 for otitis media, 669 for pancreatitis, 675 for pelvic inflammatory disease, 681 for penile/foreskin infections, 683 for peritonitis, 693 for peritonsillar abscess, 695 for pertussis, 701 for pharyngitis, 703 photosensitivity with, 706 for plague, 710, 711 for pleural effusions, 713 for pleurodesis, 713, 719 for Pneumocystis infection, 715 for pneumonia, 717 for psittacosis, 751 for pyelonephritis, 723, 763 pyloric stenosis with, 764 renal tubular acidosis with, 776 for respiratory distress syndrome, 781 for retropharyngeal abscess, 789

for rheumatic fever, 796, 797 for rickettsial infections, 327, 359, 803 for Rocky Mountain spotted fever, 805 for Salmonella infections, 813 for scarlet fever, 818, 819 for sepsis, 831, 833, 949 for septic arthritis, 835 serum sickness with, 836, 837 for short-bowel syndrome, 846 for sinusitis, 851 for staphylococcal scalded skin syndrome, 875 for Stevens-Johnson syndrome/TEN, 879 for streptococcal pharyngitis, 863 for syphilis, 843, 911 tendonitis/tendinosis with, 918 for tetanus, 923 for tick fever, 933 for toxic shock syndrome, 939 for toxoplasmosis, 941 for tracheitis, 943 for trichomoniasis, 169 for tularemia, 969 for urinary tract infections, 979 for vaginitis, 989 for Yersinia enterocolitica infection, 1023 Antibiotic-associated diarrhea, 298, 299 Antibiotic-induced rash, 341 Antibiotic prophylaxis in asplenia, 73, 830 for endocarditis, 85, 330, 331, 924–925, 995 in hydronephrosis, 463 in hyperimmunoglobulinemia E syndrome, 467 in hypogammaglobulinemia, 477 in hypoplastic left heart syndrome, 489 for meningococcal disease, 358, 359 for Pneumocystis jiroveci, 25, 61, 402, 403, 455, 714, 795, 841, 973 for sepsis, 830 in severe combined immunodeficiency, 841 in sexual abuse, 843 in sickle cell disease, 848 in ureteropelvic junction obstruction, 977

after urinary tract infection, 979 Antibody deficiency, 477, 498–499 Anticoagulants for cardiomyopathy, 153 for congestive heart failure, 221 for disseminated intravascular coagulation, 305 for hypoplastic left heart syndrome, 489 for idiopathic cavernous sinusitis, 159 for myocarditis, 619 for pulmonary embolism, 757 for pulmonary hypertension, 759 and purpura fulminans, 760, 761, 931 renal tubular acidosis with, 776 for renal venous thrombosis, 779 for stroke, 887 for thrombosis, 931 Antidepressants for abdominal migraine prophylaxis, 5 for bulimia, 142–143 for depression, 279 for hiccups, 445 for irritable bowel syndrome, 531 long QT syndrome with, 552 for obsessive-compulsive disorder, 655 for stereotypic movement disorder, 415 suicide risk with, 655, 861, 897 Antidiuretic hormone (ADH) in diabetes insipidus, 286–287, 486–487 inappropriate secretion, syndrome of, 118, 119, 482–483, 581, 587, 906–907 in portal hypertension, 731 Antiemetics for abdominal migraine, 5 for cyclic vomiting syndrome, 255 for migraine, 417 for vomiting, 1005 Antiepileptics, 825, 827, 876, 877 for abdominal migraine prophylaxis, 5 for brain vascular lesions, 993 for cyclic vomiting syndrome, 255 for hiccups, 445 for infantile spasms, 511

for migraine prophylaxis, 417 and neural tube defects, 638 for neurocysticercosis, 915 renal tubular acidosis with, 776 for seizures, 825 for seizures in fragile X syndrome, 373 for subdural hematoma, 891 suicide risk with, 825 Antifungal agents for ascariasis, 67 for aspergillosis, 71, 159 for blastomycosis, 109 for brain abscess, 119 for candidal nipple infection, 129 for candidiasis, 149, 863, 989 for cavernous sinus syndrome, 159 for chronic granulomatous disease, 191 for coccidioidomycosis, 205 for cryptococcal infections, 244, 245 for cutaneous larva migrans, 253 for diaper rash, 295 for echinococcus, 915 for fungal skin infections, 379 for histoplasmosis, 451 long QT syndrome with, 552 for meningitis, 587 for neonatal sepsis, 833 for neurocysticercosis, 915 for pinworms, 709 renal tubular acidosis with, 776 for seborrheic dermatitis, 823 for tinea capitis, 33 for trichinosis, 961 Antihistamines for allergic children, 31 for allergic rhinitis, 799 for anaphylaxis, 49 for atopic dermatitis, 82, 83 for barotitis, 99 bruising with, 138 for cholestasis, 633

for conjunctivitis, 223 for contact dermatitis, 227 for cough, 237 for cyclic vomiting syndrome, 255 for food allergy, 367 for hepatitis-related pruritus, 193 for hyperimmunoglobulinemia E syndrome, 467 long QT syndrome with, 552 for pruritus, 749 for serum sickness, 837 for status migrainosus, 417 for urticaria, 949, 983 Antihypertensives, 473 in chronic kidney disease, 195 for glomerulonephritis, 395 for hemolytic uremic syndrome, 429 for hiccups, 445 Anti-NMDA receptor encephalitis, 326, 327 Antipsychotics for fragile X syndrome, 373 for stereotypic movement disorder, 415 for tics, 935 Antiretroviral therapy, for HIV, 454, 455 Antivenom, for snake bites, 859 Anus, imperforate, 224, 225, 306, 506–507, 518 Anxiety disorders in ADHD, 86 in anorexia nervosa, 56, 57 in autism spectrum disorder, 88 in bulimia, 142 in cancer therapy, 147 in child abuse, 178 in cystic fibrosis, 259 depression with, 278 in epilepsy, 824 excoriation in, 348 generalized, 828, 860 in obesity, 652 in obsessive-compulsive disorder, 654 in polycystic ovarian syndrome, 724 in premenstrual syndrome, 740

separation, 828–829 social, 828, 829, 860–861 in stuttering, 889 substance use disorders with, 892, 893 tics in, 934 in transgender youth, 950 trichotillomania in, 962 in 22q11.2 deletion syndrome, 266, 267 Aorta, in transposition of great arteries, 956–957 Aortic coarctation, 202–203, 970 Aortic dissection, in Turner syndrome, 970, 971 Aortic insufficiency, 873, 994 Aortic regurgitation, 797 Aortic stenosis, 202, 797 Aortic valve, bicuspid, 202, 970, 971 Aortomesenteric syndrome, 898 Aortopulmonary window, 220 Apert syndrome, 460, 1044 Aphakia, 772 Aphthous ulcers, 319, 388, 412, 880 Aplasia cutis congenita, 32, 1044 Aplastic anemia, 60–61, 138, 340 Aplastic crisis, 440, 441, 676, 677, 848, 849 Apnea, 852–853 anti-seizure medication and, 825 bronchiolitis and, 134 central, 132, 630, 852 Down syndrome and, 306, 307 in floppy infant syndrome, 362, 363 in hypocalcemia, 474 of infancy, 630 in metabolic syndrome, 598 mixed, 132, 630 neonatal, 630–631 in neonatal sepsis, 832 in obesity, 652, 852, 853 obstructive (See Obstructive sleep apnea syndrome) in periodic breathing, 686–687 in pertussis, 700, 701 in pneumonia, 716 in polycystic ovarian syndrome, 724

of prematurity, 132, 630–631 in respiratory syncytial virus, 782, 783 speech problems with, 867 Apparent life-threatening event (ALTE), 132–133 Appendectomy, 62, 63 Appendiceal abscess, 46 Appendicitis, 62–63, 524 abdominal mass in, 2, 3 abdominal pain in, 6–7, 62 intestinal obstruction in, 518, 519 mesenteric adenitis vs., 590, 591 Appendix testis, torsion of, 921 Applied behavior analysis (ABA), 89 Apraxia, 866 Aquagenic urticaria, 982 Aqueductal stenosis, 460 Arachnoid cysts, 460 Arbovirus encephalitis, 1012–1013 Arcus corneae, 470 Arterial malformations, 420–421 Arteriovenous fistula (AVF), 420, 472 Arteriovenous malformations (AVMs), 420–421, 992–993 heart failure with, 220 hemoptysis with, 432 in hypoplastic left heart syndrome, 489 intracranial hemorrhage with, 522, 523 polycythemia with, 726, 727 Arthritis. See also specific conditions causing crying in, 242 enthesitis-related, 64, 872–873 gonococcal, 400, 401 juvenile idiopathic, 64–65, 96, 97, 154 Lyme disease, 558, 559 psoriatic, 64, 752, 872–873 reactive, 222, 257, 316, 370, 872–873, 1023 rheumatoid, 64–65, 72 septic, 92, 509, 663, 834–835 Arthrogryposis, 284, 362, 632, 868 Arthrogryposis multiplex congenita, 1044 Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, 632 Arthus reaction, 837, 985

Artichoke leaf extract, 531 Articulation disorders, 866 Ascariasis, 66–67, 518 Ascaris lumbricoides, 66–67 Ascites, 68–69, 322, 323 abdominal mass with, 2, 3 atelectasis with, 80 in biliary atresia, 105 in cirrhosis, 196 jaundice with, 68, 532 in myocarditis, 618 in nephrotic syndrome, 68, 69, 636 in pancreatic pseudocyst, 672, 673 in pancreatitis, 68, 674, 675 in peritonitis, 69, 322, 323, 692, 693 in polycystic kidney disease, 722 in portal hypertension, 68, 730, 731 proteinuria with, 746 in Wilson disease, 1018 Aseptic meningitis, 586, 587, 610, 611, 807, 933 Aseptic necrosis of femoral head, 92–93 Aseptic sinus thrombosis, 158 Askin tumor, 346 Aspergilloma, 70–71 Aspergillosis, 70–71 candidiasis with, 149 cavernous sinus syndrome in, 158, 159 in cystic fibrosis, 70, 258, 259 disseminated intravascular coagulation in, 304 meningitis in, 586 otitis externa in, 666 Aspergillus, 70. See also Aspergillosis Asphyxia, 282, 304 Aspiration, 354, 355 amniotic fluid, 304 foreign body, 30, 80–81, 236–237, 240, 432, 1014, 1015 meconium, 580–581, 696 Aspirin (salicylate) poisoning, 20, 810–811 Asplenia, 72–73 babesiosis with, 73, 94 epiglottitis with, 338

meningococcemia with, 588 sepsis with, 830 sickle cell disease with, 848 Asthma, 30–31, 74–77, 1068–1069 allergic rhinitis and, 74, 798 aspergillosis in, 70 atelectasis in, 80–81 cor pulmonale in, 232 cough in, 236–237 food allergy with, 366 gastroesophageal reflux in, 382 obesity and, 652 pneumothorax in, 718, 719 respiratory syncytial virus and, 783 three R’s of, 74 wheezing in, 74, 75, 1014, 1015 Astigmatism, 772–773, 1056 Astrocytoma, 122, 966, 967 Ataxia, 78–79, 408 Ataxia telangiectasia, 22, 78, 498 Ataxia telangiectasia syndrome, 1044 Ataxic cerebral palsy, 78, 166 Atelectasis, 80–81, 258, 259, 580, 701, 780, 943 Atlantoaxial instability, 307 Atopic dermatitis, 30–31, 82–83, 226, 294, 822 allergic rhinitis with, 798 asthma with, 74 food allergy with, 366 pruritus with, 82, 748 Atrial flutter, 901 Atrial septal defect (ASD), 84–85, 220, 306 Atrial tachycardia, 900 Atrioventricular conduction, 1038 Atrioventricular nodal reentry tachycardia (AVNRT), 900 Atrioventricular reciprocating tachycardia (AVRT), 900 Atrioventricular regurgitation, 220 Attention-deficit/hyperactivity disorder (ADHD), 86–87, 88 bladder and bowel dysfunction in, 106 depression in, 278 developmental delay vs., 283 epilepsy and, 824

incontinence in, 262, 332 intellectual disability with, 516 learning disabilities with, 86, 546 neurofibromatosis and, 642 in NICU graduates, 365 social anxiety with, 860 stuttering in, 888 substance use disorders with, 892, 893 tics with, 86, 934, 935 Turner syndrome and, 970 22q11.2 deletion syndrome and, 266 Atypical mycobacterial infections, 622, 648–649 Auditory processing disorder, 546 Aura in migraine, 416 in seizure, 824 Aural diphtheria, 300 Aural neuralgia, 319 Auricle cellulitis of, 318 trauma to, 318 Autism spectrum disorder, 86, 88–89, 106, 266 developmental delay vs., 283 feeding disorders in, 354 in fragile X syndrome, 372 intellectual disability with, 88, 89, 516 language or speech problems in, 88, 864, 866, 867 in NICU graduates, 365 stereotyped behaviors in, 88, 414 trichotillomania in, 962 tuberous sclerosis and, 966 Autoimmune encephalitis, 326 Autoimmune gastritis, 380 Autoimmune glomerulonephritis, 394 Autoimmune hemolytic anemia, 90–91, 424–425 Autoimmune hepatitis, 2, 20, 192, 196, 197, 436, 532, 533 Autoimmune lymphoproliferative syndrome (ALPS), 564–565 Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), 498 Autoimmune thyroiditis, 162, 492, 970 Automated external defibrillator (AED), 552 Automatic tachycardia, 900, 901

Autosomal dominant polycystic kidney disease (ADPKD), 194, 722–723 Autosomal recessive (AR) ataxia, 78 Autosomal recessive hyper IgM syndromes (AR-HIGM), 477 Autosomal recessive polycystic kidney disease (ARPKD), 194, 218, 722–723 Avascular necrosis of femoral head, 92–93, 835, 848, 849, 855 Avoidant restrictive food intake disorder (ARFID), 354 Awake bruxism, 140 Axenfeld-Rieger syndrome, 392, 1044 Axonotmesis, 116 Azoospermia, cancer therapy and, 147 Azotemia, 18, 518, 519 B Babesia microti, 73, 94 Babesiosis, 73, 94–95, 361 BabyBIG, 371 Bacillary angiomatosis, 157 Bacillary peliosis, 157 Bacillus anthracis, 58–59 Bacillus Calmette-Guérin (BCG) vaccine, 964 Bacillus cereus, 370, 1063 Back pain, 96–97, 820, 821 “Back to Sleep,” 365, 631, 894 Baclofen withdrawal, 16 Bacteremia in anaerobic infections, 47 in asplenia, 73 in breast abscess, 127 in Campylobacter infections, 145 in cellulitis, 164, 688, 689 in endocarditis, 330–331 in epiglottitis, 339 in meningococcemia, 588 in neonatal sepsis, 833 in osteomyelitis, 662 in peritonitis, 692 in pneumonia, 717 in Salmonella infections, 812, 813 in stomatitis, 881 in urinary tract infection, 978 in Yersinia enterocolitis infection, 1022 Bacterial encephalitis, 326. See also Encephalitis

Bacterial meningitis, 326–327, 358, 359, 586–587 Bacterial overgrowth, 188, 189, 298, 846, 847 Bacterial pneumonia, 716–717 Bacterial rhinosinusitis, 850 Bacterial vaginosis, 168, 681, 988, 989, 1062 Bacteroides, 46, 47, 126, 656, 692 Balanitis, 316, 682, 683 Balanoposthitis, 682, 683 Bannayan-Riley-Ruvalcaba syndrome (BRRS), 728 Barbiturate coma, 327 Barbiturate withdrawal, 16–17 Bardet-Biedl syndrome, 194, 218, 652, 1044 Bariatric surgery, 599, 653 Barlow test, 284 Barotitis, 98–99 Barotrauma, 98–99, 318, 319 Barrier contraceptives, 229, 230 Barth syndrome, 1044 Bartonella henselae, 156 Bart syndrome, 1044 Bartter syndrome, 480, 481, 482 Basal cell nevus syndrome, 1044 Bath salts, 902 Bazex-Dupré-Christol syndrome, 604, 605 B-cell lymphoma, 646, 1020 Beaded hair, 32 Becker muscular dystrophy, 614–615 Beckwith-Wiedemann syndrome, 1045 abdominal mass with, 2 ankyloglossia with, 52 chronic kidney disease with, 194 diaphragmatic hernia with, 296 hypoglycemia with, 478, 586, 597 rhabdomyosarcoma with, 794 Wilms tumor with, 1016 Bedwetting (nocturnal enuresis), 106, 262, 328, 332–333 Beef tapeworm, 914–915 Bee sting, 858 Behçet syndrome, 316, 360, 880, 1045 Bell-clapper deformity, 920 Bell palsy, 100–101, 319, 340, 575, 611

Benign paroxysmal vertigo of childhood, 416 Benzodiazepines for abdominal migraine, 5 abuse of, 892 for cyclic vomiting syndrome, 255 for hemolytic uremic syndrome, 429 for neonatal abstinence syndrome, 627 for opioid withdrawal, 17, 659 poisoning (suicide), 897 for seizures, 327, 825, 827 for seizures in encephalitis, 327 for social anxiety disorder, 861 for status epilepticus, 877 for stereotypic movement disorder, 415 for sympathomimetic poisoning, 903 for tetanus, 923 Benzodiazepine withdrawal, 16–17 β2-Agonists, for asthma, 75–76 β-Blockers for cardiomyopathy, 153 for cavernous transformation, 161 for chronic kidney disease, 195 for cirrhosis, 197 for congestive heart failure, 221 for cyclic vomiting syndrome, 255 for glaucoma, 393 for Graves disease, 405 for hypertension, 473 for long QT syndrome, 553 for migraine prophylaxis, 417 for myocarditis, 619 for portal hypertension, 730 for renal artery stenosis, 775 for supraventricular tachycardia, 901 for sympathomimetic poisoning, 903 for tetanus, 923 for tetralogy of Fallot, 924 for ventricular tachycardia, 997 β-thalassemia, 72, 424, 670, 926–927 Bethlem muscular dystrophy, 614 Bezoars, 102–103, 518, 962, 963, 1004

Bezold abscess, 575 Bicuspid aortic valve, 202, 970, 971 Bile acid-binding resins, 471 Bile acid synthetic defects (BASDs), 632, 633 Biliary atresia (BA), 104–105 cirrhosis with, 196, 197 hepatomegaly with, 436 jaundice with, 104, 532, 533 neonatal cholestasis with, 632–633 Biliary atresia splenic malformation (BASM), 632 Biliary obstruction, 2, 3, 450, 532, 533 Biliary tract mass, 2–3 Bilirubin. See Hyperbilirubinemia; Jaundice Bilirubin encephalopathy, 426, 427, 535 Bilirubin-induced neurologic dysfunction (BIND), 535 Binge eating, in bulimia, 142–143 Biotinidase deficiency, 592 Bipolar disorder, depression in, 278 Birth trauma Bell palsy vs., 100 brachial plexus palsy in, 116–117 conjunctivitis vs., 222 hypopituitarism in, 486 subdural hematoma in, 890 2,3-Bisphosphoglycerate mutase deficiency, 726 Bisphosphonates, 93, 281, 449, 465, 661 Bites. See also Mosquitoes; Tick-borne illnesses insect, 48, 748, 858–859 mammalian, 572–573, 766–767 snake, 858–859 Bite wounds cellulitis prophylaxis in, 165 infections of, 46, 47, 73, 572 Black measles, 577 Blackwater fever, 568 Black widow spider, 858, 859 Bladder neurogenic, 2, 194, 262, 637, 638 overactive, 107, 262 underactive, 106, 262 Bladder and bowel dysfunction (BBD), 106–107, 262, 978, 998, 999

Bladder exstrophy, 350–351, 514 Bladder mass, 2–3 Bladder outlet obstruction, 976 Bladder toxicity, in cancer therapy, 146 Blalock-Taussig systemic-to-pulmonary artery shunt, 925 Bland-White-Garland syndrome, 54 Blastomyces dermatitidis, 108 Blastomycosis, 108–109, 360 Blau syndrome, 814–815 Bleach bath, for atopic dermatitis, 82 Bleeding abnormal, 8–9 lower gastrointestinal, 554–555 upper gastrointestinal, 974–975 Blepharitis, 110–111, 222 Blindness. See also Vision stereotypic movement disorder in, 414 Bloch-Sulzberger syndrome, 1045 Blood pressure high (See Hypertension) low (See Hypotension) measurement of, 1033–1037 Blood transfusion acute reaction to, 304, 948–949 for anemia of chronic disease, 51 for aplastic anemia, 61 for autoimmune hemolytic anemia, 91 delayed reaction to, 948–949 for dengue infection, 269 for Ebola virus disease, 321 for G6PD deficiency, 397 for hemolysis, 425 for hemolytic disease of fetus or newborn, 427 for hemolytic uremic syndrome, 429 for hyperleukocytosis, 469 for immunoglobulin A deficiency, 502–503 for microcytic anemia, 603 for pallor, 671 for rickettsial disease, 803 for sickle cell disease, 848, 849 for thalassemia, 927

for transient erythroblastopenia of childhood, 953 Blood type compatibility, 426 Bloom syndrome, 22, 664, 706, 707, 1045 Blount disease, 652, 653 Blue diaper syndrome, 464, 1045 “Blue tets,” 924 Bochdalek hernia, 296 Body dysmorphic disorder, 348 Body lice, 550–551 Body mass index (BMI), 652–653 Bone blastomycosis, 108 Bone marrow failure syndromes, 60, 644 Bone marrow transplantation, 112–113 for acute lymphoblastic leukemia, 23 for aplastic anemia, 61 donor selection in, 112 graft-versus-host disease in, 402–403 splenic function in, 72 for thalassemia, 927 Bone toxicity, in cancer therapy, 146 Bordetella parapertussis, 700 Bordetella pertussis, 700 Borrelia burgdorferi, 558–559 Boston exanthem, 412 Botulism, 46, 47, 114–115, 363, 370–371, 616 Bourneville disease. See Tuberous sclerosis complex Bovine spongiform encephalopathy, 744, 745 Bowel dysfunction, 106–107, 978, 998, 999 Bowel infarction, 68, 519 Bowel management, 107 Bowel necrosis, 524, 525, 624, 625, 1003 Bowel obstruction, 518–519, 1003, 1004 cancer therapy and, 147 with inguinal hernia, 515 Bowel perforation, 519, 524, 525, 624 Bowleggedness, 520 Brachial plexus palsy, perinatal, 116–117 Brachmann-De Lange syndrome, 1045 Bracing for anterior knee pain, 539 for clubfoot, 200–201

for hip dysplasia, 285 for Perthes disease, 699 for scoliosis, 821 for spinal muscular atrophy, 869 for thoracic insufficiency syndrome, 929 Brain abscess, 46, 47, 118–119, 851, 940 Brain death, 208 Brain herniation, 523 Brain injury. See also Encephalopathy in diabetic ketoacidosis, 293 traumatic, 120–121, 214–215 Brain lesions, congenital vascular, 992–993 Brain tumor, 122–123 cancer therapy and, 147 hydrocephalus with, 460 tuberous sclerosis and, 122, 966 Branchial cleft cyst, 622 Branchial cleft malformations, 124–125 Branchio-oto-renal syndrome, 194, 1045 Breast abscess, 126–127 Breast cellulitis, 164 Breast development, premature, 738–739 Breast engorgement, 126, 128, 129 Breast enlargement, male, 410–411 Breastfeeding, 128–129 abscess with, 126–127 ankyloglossia and, 52–53, 128, 129 asthma reduced in, 77 cleft lip/palate and, 199 colic and, 207 contraindications to, 128 HIV and, 454 infant conditions interfering with, 128 iron in, 526 jaundice in, 532, 534–535 mastitis with, 126–127, 128, 129 maternal conditions interfering with, 128 necrotizing enterocolitis and, 624 neonatal alloimmune thrombocytopenia and, 629 obesity prevention in, 652 opioid withdrawal and, 627

risks of not, 128 Breath-holding spells, 130–131, 132, 905 Breech birth, 284 Brief resolved unexplained event (BRUE), 132–133, 178, 686 Brill-Zinsser disease, 802 Bronchiectasis cough with, 236, 237 in cystic fibrosis, 258, 259 hemoptysis with, 432, 433 in immune deficiency, 499 Bronchiolitis, 80, 134–135, 782–783 Bronchiolitis obliterans, 27 Bronchitis, 236, 237, 259 Bronchodilators for asthma, 75–76, 237 for atelectasis, 81 for bronchopulmonary dysplasia, 137 for cor pulmonale, 233 for cystic fibrosis, 259 for food allergy, 367 for reactive airway disease, 237 for respiratory syncytial virus, 783 for wheezing, 1015 Bronchogenic cyst, 80, 432, 622 Bronchomalacia, 1014, 1015 Bronchopulmonary dysplasia (BPD), 136–137, 232, 781 Bronchopulmonary fistula, 719 Brown recluse spider, 858, 859 Brown syndrome, 883 Brucellosis, 360, 361, 370–371, 1063 Brudzinski sign, 586 Brugada syndrome, 996 Bruising, 138–139, 178, 242 Bruxism, 140–141 Bubble bath urethritis, 316 Buboes, 710, 711 Bubonic plague, 710–711 Buccal cellulitis, 164 Buckley syndrome, 467 Budd-Chiari syndrome, 2, 20, 436, 437, 692, 730, 930 Bulimia, 142–143, 892, 1004, 1010

Bullous impetigo, 508 Buried penis, 682 Burkholderia cepacia, 258, 259 Burkitt lymphoma, 340, 646 Burn injuries, 178, 304 Bursitis, 538, 918 Butterbur, 417 Byler disease. See Progressive familial intrahepatic cholestasis C C1 esterase deficiency, 212, 213, 322, 323, 338, 438–439 Café au lait spots, 642 Caffeine for apnea of prematurity, 631 avoiding, in polycystic kidney disease, 723 for bronchopulmonary dysplasia, 136 for periodic breathing, 687 for respiratory distress syndrome, 780 Caffeine toxicity, 902, 903 Caffeine withdrawal, 16–17 Caffey disease, 1045 Caisson disease, 92 Calcaneovalgus, 200 Calcinosis, 280, 281 Calcium channel blockers for cardiomyopathy, 153 for glomerulonephritis, 395 for hemolytic uremic syndrome, 429 for hypertension, 473 for migraine prophylaxis, 417 for polycystic kidney disease, 723 for pulmonary hypertension, 759 for Raynaud phenomenon, 914 for renal artery stenosis, 775 for sympathomimetic poisoning, 903 for urticaria, 983 Calcium imbalance. See Hypercalcemia; Hypocalcemia Calcium supplementation for dermatomyositis/polymyositis, 281 for hypocalcemia, 475 for lactose intolerance, 543 for osteogenesis imperfecta, 661

for Perthes disease, 699 for rickets/osteomalacia, 801, 1065 Calculi. See Cholelithiasis; Nephrolithiasis; Urolithiasis California (LaCrosse) encephalitis, 1012 Campbell-Williams syndrome, 1015 Campomelic dysplasia, 1045 Campylobacter infections, 144–145, 370–371, 408, 1063 Canavan disease, 1045 Cancer. See also specific types candidiasis in, 148 intestinal obstruction in, 518 intracranial hemorrhage in, 522 late effects of therapy, 146–147 Candidal dermatitis, 226, 294–295 Candidal nipple infection, 128, 129 Candidemia, 148, 149 Candidiasis, 148–149, 226 chronic mucocutaneous, 499 cutaneous, 148, 149, 378–379 in diabetes mellitus, 288 diaper rash, 148, 294–295, 840 dysuria in, 316 epiglottitis in, 338 esophageal, 148, 149, 455, 863 gingivitis in, 390 in immune deficiency, 498, 499, 840 meningitis in, 586 oral (thrush), 128, 148, 149, 294, 499, 840 osteomyelitis in, 662 otitis externa in, 666 vaginal, 148, 149, 288, 316, 988, 989, 1062 vulvovaginal, 148, 149, 988, 989 Capillary malformations, 420–421 Carbonic anhydrase inhibitors for glaucoma, 393 for idiopathic intracranial hypertension, 497 renal tubular acidosis with, 776 Carbon monoxide poisoning, 150–151, 904 Carboxyhemoglobin, 150–151, 726 Cardiac arrhythmias breath-holding spells and, 130, 131

cancer therapy and, 146 cardiomyopathy and, 152–153 chest pain in, 172 congestive heart failure in, 220–221 dehydration and, 264 drowning and, 308 hypocalcemia and, 475 hypokalemia and, 480, 481 long QT syndrome and, 552–553 muscular dystrophy and, 615 myocarditis and, 618, 619 obstructive sleep apnea and, 853 pulmonary hypertension and, 758 rhabdomyolysis and, 793 status epilepticus and, 876 supraventricular tachycardia and, 900–901 syncope in, 904 systemic sclerosis and, 914 toxic shock syndrome and, 939 ventricular tachycardia and, 996–997 West syndrome and, 510 Cardiac catheterization, 1041–1042 Cardiac hemolysis, 424, 425 Cardiac output, 1042 Cardiac rhabdomyoma, 966, 967 Cardiac tamponade, 220, 582, 647, 684, 685 Cardiogenic shock, 528 Cardiology laboratory, 1032–1042 Cardiomegaly, 80, 1041 Cardiomyopathy, 152–153, 220 adenovirus infection and, 26, 27 cancer therapy and, 146, 152 chest pain in, 172 hypertrophic, 172 inborn errors of metabolism and, 592, 594, 595, 596 muscular dystrophy and, 614, 615 tachycardia and, 152–153, 901, 996 Wilson disease and, 1018, 1019 Cardiopulmonary resuscitation (CPR), 308–309 Cardiothoracic ratio, 1041 Cardiotoxicity, in cancer therapy, 146, 152

Carnitine deficiency, 847 Caroli disease, 218, 632, 722, 1045 Carotid-cavernous fistulas, 158, 159 Carpenter syndrome, 678 Cartilage-hair hypoplasia, 446 Castleman disease, 564–565 Cast syndrome, 898 Cataplexy, 620–621 Cataract, 154–155 amblyopia with, 40, 154, 155 cancer therapy and, 147 congenital, 154–155, 392 Down syndrome and, 154, 306, 307 Ebola virus and, 321 Cat bites, 572–573 Cat eye syndrome, 1045 Catheter-related endocarditis, 330, 331 Catheter-related peritonitis, 148 Cat-scratch disease, 156–157 conjunctivitis in, 222 fever on unknown origin in, 360, 361 hypercalcemia in, 464 neck masses in, 622, 623 parotitis in, 611 Cauliflower ear, 319 Cautery, for nosebleeds, 651 Cavernous malformations, 992–993 Cavernous sinus syndrome, 158–159 Cavernous sinus thrombosis, 275, 851 Cavernous transformation, 160–161 Cavities (dental caries), 266, 270–273 Celiac crisis, 162 Celiac disease, 162–163, 387 dermatomyositis in, 280 diabetes mellitus with, 288 diarrhea in, 188, 189, 298, 299, 376 Down syndrome and, 162, 306, 307 feeding disorders in, 354 gastritis in, 380 gastroesophageal reflux in, 382 immunoglobulin A deficiency with, 502

immunoglobulin A nephropathy in, 504 malabsorption in, 162, 566–567, 844 short stature in, 844 splenic function in, 72 Turner syndrome and, 162, 970 weight loss in, 1010 Cellulitis, 127, 164–165, 509 contact dermatitis vs., 226 dental infection and, 275 earache in, 318 edema and, 323 in hyperimmunoglobulinemia E syndrome, 466 lymphedema and, 562, 563 MRSA, 164–165 in necrotizing enterocolitis, 624, 625 orbital, 164, 165, 541, 688, 851 penile, 683 periorbital (preseptal), 164, 222, 688–689, 851 peritonsillar, 694 warts and, 1009 Cellulitis-adenitis syndrome, 164 Central apnea, 132, 630, 852 Central hypothyroidism, 494 Central hypotonia, 362–363 Central line-associated bloodstream infection (CLABSI), 846 Central pontine myelinolysis (CPM), 907 Central precocious puberty, 734–735 Cerebellitis, 611 Cerebral contusion, 890, 891 Cerebral edema in diabetic ketoacidosis, 293 in encephalitis, 327 high-altitude, 36–37 in hyponatremia, 482 in stroke, 887 Cerebral hemorrhage, 282 Cerebral malaria, 568, 569 Cerebral palsy (CP), 166–167 ataxic, 78, 166 developmental delay vs., 283 dyskinetic, 166

feeding disorders in, 354 follow-up in NICU graduates, 364 gastroesophageal reflux in, 382 intellectual disability with, 516 overdiagnosis in premature infants, 167 persistent pulmonary hypertension of newborn with, 696 spastic, 166 speech problems in, 866 stereotypic movement disorder in, 414 Cerebral salt wasting, 906, 907 Cerebral sinovenous thrombosis (CSVT), 930 Cerebrocostomandibular syndrome, 928 Cerumen, impacted, 318 Cervical adenitis, 46, 622–623 Cervical cancer, 456–457 Cervical lymphadenopathy, 622–623 Cervical sinus, persistence of, 124 Cervical wattle, 622 Cervicitis, 168–169, 316, 400, 401, 989 Chalazion, 110 Chamomile, 531 Chancroid, 170–171, 443 Charcot-Marie-Tooth disease, 1045 CHARGE syndrome, 194, 198, 944, 1045 Char syndrome, 678 Chédiak-Higashi syndrome, 498–499, 1045 Chelation therapy, 529, 545, 603, 927, 949, 1019 Chemical conjunctivitis, 222, 223 Chemical epididymitis, 336 Chemotherapy for acute lymphoblastic leukemia, 23 for acute myeloid leukemia, 25 for brain tumors, 123 for Ewing sarcoma, 346–347 for germ cell tumors, 385 for Hodgkin lymphoma, 453 for hyperleukocytosis, 469 late effects of, 146–147 for neuroblastoma, 641 neurologic toxicity of, 147 for non-Hodgkin lymphoma, 647

for osteosarcoma, 664–665 ototoxicity of, 147 renal toxicity of, 147 renal tubular acidosis with, 776 reproductive toxicity of, 147 for retinoblastoma, 785 for rhabdomyosarcoma, 795 subsequent neoplasms with, 147 for Wilms tumor, 1017 Chest pain, 172–173 in costochondritis, 234–235 in lupus erythematosus, 172, 556 in myocarditis, 618 in pericarditis, 684 in pleural effusion, 712 in pneumothorax, 172, 718 in pulmonary embolism, 756, 757 in spondyloarthropathy, 873 Chest physiotherapy, 81, 259, 869 Chest roentgenogram (x-ray), 1041 Chiari malformation, 78, 460, 637, 638 Chickenpox, 174–175. See also Varicella Chikungunya virus, 176–177 Child abuse apnea in, 631 brief resolved unexplained event in, 133, 134, 178 bruising in, 138, 178 colic and, 207 contact dermatitis vs., 227 crying in, 242, 243 depression in, 278 diaper rash in, 295 drowning and, 308 emotional, 178 head banging vs., 414 medical, 478, 612–613 physical, 178–179 sexual (See Sexual abuse) subdural hematoma in, 890–891 Chlamydia (Chlamydia trachomatis infection), 180–181, 182 cervicitis in, 168–169, 989

conjunctivitis in, 180–181, 222, 223 dysuria in, 316, 317 epididymitis in, 180, 336, 337 gonococcal coinfection with, 400, 401, 703 pelvic inflammatory disease in, 680, 681, 989 pneumonia in, 180–181, 222, 716 sexual abuse and, 180, 842–843 vaginitis in, 988 Chlamydia psittaci, 180, 182, 750 Chlamydophila pneumoniae, 180, 182–183 Chloride diarrhea, congenital, 480 Cholangitis in anaerobic infections, 46, 47 in biliary atresia, 104, 105 cirrhosis with, 196, 197 in congenital hepatic fibrosis, 218, 219 in Crohn disease, 238 in cryptosporidiosis, 248 gallstones and, 185 hepatitis with, 192 hepatomegaly in, 436 in histiocytosis, 448, 449 jaundice with, 532 neonatal cholestasis with, 632, 633 in polycystic kidney disease, 722 portal hypertension with, 730 portal vein obstruction in, 160 sclerosing, 104, 192, 196, 197, 248, 436 in ulcerative colitis, 972 Cholecystectomy, 441 Cholecystitis, 184, 185 with cryptosporidiosis, 248 with enteric fever, 813 with hemolysis, 425 with sickle cell disease, 849 Choledochal cyst, 2 Cholelithiasis (gallstones), 184–185 cancer therapy and, 146 Crohn disease and, 239 gallstone ileus in, 185 hemolysis and, 425

in hereditary spherocytosis, 440, 441 in obesity, 652, 653 pancreatitis with, 184, 185, 674, 675 in short-bowel syndrome, 847 in thalassemia, 927 Cholera, 186–187, 370–371 Cholestasis, 104–105 in cystic fibrosis, 259 hepatomegaly in, 436, 437 in necrotizing enterocolitis, 625 neonatal, 632–633 in polycystic kidney disease, 722 progressive familial intrahepatic, 192 in short-bowel syndrome, 847 Cholesterol, elevated levels of, 470–471, 598–599. See also Hyperlipidemia Cholinergic urticaria, 982 Chondroblastoma, 92 Chondrodysplasia, 464 Chondrodysplasia punctata 2, X-linked dominant, 1045 Chondrolysis, 855 Chondromalacia patella, 539 Chordee, 490, 682 Chorea, 796, 934 Chorioamnionitis, 136, 580, 581, 656, 696 Choriocarcinomas, 384–385 Chorioretinitis, 442, 940, 941 Choroid plexus tumors, 122 Chronic diarrhea, 188–189, 298 Chronic disease anemia of, 50–51, 195, 602 liver disease associated with, 192 short stature in, 845 Chronic granulomatous disease (CGD), 190–191, 498 Chronic hepatitis, 192–193 Chronic inflammatory demyelinating polyneuropathy (CIDP), 408 Chronic kidney disease (CKD), 50–51, 194–195 Chronic lymphocytic thyroiditis, 492, 493 Chronic mucocutaneous candidiasis, 498–499 Chronic nonspecific diarrhea of childhood, 376–377 Chronic pancreatitis, 674 Chronic pyelonephritis, 762, 763

Chronic wasting disease of cervids, 744 Chuvash polycythemia, 726 Chvostek sign, 474 Chylothorax, 450, 451, 712, 713 Chylous reflux syndromes, 563 Cigarette/nicotine dependence, 893 Ciliary dyskinesia, 80, 236, 237, 1051 Circulatory overload, transfusion-associated, 948–949 Circumcision, 491, 682, 683, 705, 762, 978 Cirrhosis, 196–197 α1-antitrypsin deficiency and, 34, 35, 196 ascites in, 68, 196 cystic fibrosis and, 196, 197, 258 edema in, 322 hepatitis and, 192, 196–197, 1001 hepatomegaly in, 196, 436 peritonitis with, 692 portal hypertension in, 730–731 portal vein obstruction in, 160 in short-bowel syndrome, 847 Citrin deficiency, 632 Clary sage oil, for impetigo, 509 Cleft lip and palate, 198–199, 486, 578 Clinical reasoning, 1031 Clitoromegaly, 38, 216 Cloacal exstrophy, 350, 506 Clogged milk ducts, 128, 129 Clostridium, 46 Clostridium botulinum, 114 Clostridium difficile, 189, 256, 257, 298, 299 Clostridium perfringens, 656, 1063 Clostridium sordellii, 656 Clostridium tetani, 656, 922 Clubfoot, 200–201, 638 Cluster headache, 158, 416 Coagulation disorders, 8, 138. See also specific disorders Coal tar, 753, 823 Coarctation of aorta, 202–203, 970 Coates disease, 614 Cobalamin (vitamin B12) deficiency, 584–585, 847 Cobalamin (vitamin B12) supplementation, 915

Cocaine, 172, 892, 902, 903, 996 Coccidioidomycosis, 204–205, 360, 586 Cockayne syndrome, 706, 1045 Coenzyme Q10, 79, 255, 417 Coffin-Lowry syndrome, 621, 1045 Cognitive behavioral therapy (CBT) for abdominal migraine, 5 for ADHD, 87 for autism spectrum disorder, 89 for bulimia, 142–143 for depression, 279 for enuresis, 333 for excoriation disorder, 349 for irritable bowel syndrome, 531 for obsessive-compulsive disorder, 654 for separation anxiety disorder, 829 for social anxiety disorder, 860 for substance use disorders, 893 Cognitive biases, 1031 Cohen syndrome, 652, 1045 Coining, 138, 178, 358 Cold injury, 374–375 Cold shock, 830, 831 Cold urticaria, 982 Cole-Carpenter syndrome, 1045 Colic, 206–207, 242, 545 Colitis allergic, 554 amebic, 42–43 lower GI bleeding in, 554–555 neutropenic, 554 ulcerative, 770, 972–973 Collagenous gastritis, 380 Collagenous sprue, 163 Coloboma, 772 Colorado tick fever (CTF), 932–933 Colorectal cancer, 728–729 Coma, 208–209, 1061 in encephalitis, 1013 in inborn errors of metabolism, 592, 594, 595, 596 in lead poisoning, 544, 545

in malaria, 568 in meningococcemia, 589 myxedema, 493 in rabies, 766 Combined oral contraceptive pills (COCs), 228, 231, 313 Common variable immunodeficiency (CVID), 210–211, 476, 498–499, 503 Common warts, 1008 Communication (speech) problems, 866–867 Compartment syndrome, 431, 793, 885 Compensated cirrhosis, 196 Complementary and alternative therapy for acne, 15 for ADHD, 87 for alopecia, 33 for autism spectrum disorder, 89 for back pain, 97 for bladder and bowel dysfunction, 107 for blepharitis, 111 for breastfeeding, 129 for bruxism, 141 for chronic kidney disease, 195 for colic, 207 for diskitis, 303 for dysmenorrhea, 313 for encopresis, 329 for feeding disorders, 355 for food poisoning, 371 for headache and migraine, 417 for hiccups, 445 for irritable bowel syndrome, 531 for pleural effusion, 713 for seborrheic dermatitis, 823 for transverse myelitis, 959 for vaginitis, 989 Complement deficiency, 212–213, 498, 588 Complete androgen insensitivity syndrome (CAIS), 38 Complete plexus injury, 116 Complete primary repair of exstrophy (CPRE), 351 Complex decongestive physiotherapy (CDP), 563 Compulsions, 654 Concussion, 120–121, 214–215

Condoms, 229, 230 Conduct disorder, 86, 278, 892, 934 Condylomata acuminata, 456–457 Confusional migraine, 416 Congenital adrenal hyperplasia (CAH), 216–217, 742–743, 1066 acne in, 12 ambiguous genitalia in, 38–39, 743 hypokalemia in, 480, 481 premature adrenarche in, 737 Congenital amegakaryocytic thrombocytopenia, 1045 Congenital anomalies of kidney and urinary tract (CAKUT), 194, 316, 317 Congenital cataracts, 154–155, 392 Congenital central hypoventilation syndrome, 132, 446, 640, 852 Congenital chloride diarrhea, 480 Congenital cutaneous candidiasis, 148 Congenital cytomegalovirus, 260–261, 364 Congenital diaphragmatic hernia (CDH), 80, 237, 296–297, 382, 696, 928, 1002 Congenital erythropoietic porphyria (CEP), 706 Congenital glaucoma, 222, 392–393 Congenital heart disease (CHD), 364. See also specific defects congestive heart failure and, 220 Down syndrome and, 306, 307 endocarditis prophylaxis in, 330 esophageal atresia/TEF with, 944 feeding disorders in, 354 follow-up of NICU graduates, 364–365 hemoptysis in, 432 intracranial hemorrhage in, 522 malrotation with, 1002 polycythemia in, 726, 727 stroke in, 886 supraventricular tachycardia in, 900 thrombosis in, 930 weight loss in, 1010 Congenital hepatic fibrosis (CHF), 218–219 Congenital hydrocephalus, 460 Congenital hypothyroidism, 282, 494–495 Congenital insensitivity to pain, 1045 Congenital iris ectropion syndrome, 392 Congenital lymphedema, 562 Congenital methemoglobinemia, 600–601

Congenital milia, 604–605 Congenital muscular dystrophy, 614–615 Congenital myasthenia, 616–617 Congenital nephrotic syndrome, 194, 636 Congenital rubella syndrome, 386–387, 516, 678 Congenital scoliosis, 928 Congenital splenic cyst, 2 Congenital syphilis, 910–911 Congenital toxoplasmosis, 940–941 Congenital tuberculosis, 964, 965 Congenital varicella syndrome, 174, 175 Congenital vascular brain lesions, 992–993 Congestive heart failure (CHF), 220–221 adenovirus infection and, 27 anomalous coronary artery and, 54 aortic coarctation and, 202, 203 atrial septal defect and, 85 cardiomyopathy in, 152 edema in, 322, 323 hepatomegaly in, 436 hypoplastic left heart syndrome and, 488 obstructive sleep apnea and, 853 patent ductus arteriosus and, 220, 678, 679, 781 peritonitis in, 692 persistent pulmonary hypertension of newborn and, 697 persistent tachycardia and, 901 transient erythroblastopenia of childhood and, 953 ventricular septic defects and, 994, 995 weight loss in, 1010 Wilson disease and, 1018 Conjugated hyperbilirubinemia, 532–533, 534 Conjunctival diphtheria, 300 Conjunctivitis, 222–223 adenovirus, 26–27, 222, 223 allergic, 30, 798 cellulitis vs., 164 chlamydia, 180–181 fever of unknown origin with, 361 gonococcal, 222, 223, 400, 401 herpes simplex, 442, 443 immunoglobulin A deficiency and, 502

lacrimal duct obstruction and, 541 measles, 222, 576 respiratory syncytial virus, 782 sore throat with, 862 tularemia and, 969 Conotruncal anomaly face syndrome, 198 Conradi syndrome, 154 Constipation, 106, 224–225 crying in, 242 daytime incontinence with, 262 diarrhea associated with, 376 in Down syndrome, 307 dysuria with, 316 encopresis in, 328–329 in Hirschsprung disease, 224, 225, 446, 447 in irritable bowel syndrome, 530–531 rectal prolapse with, 770 in renal tubular acidosis, 777 Constitutional delay of growth and puberty (CDGP), 754–755, 844–845 Constitutional language delay, 864, 865 Constrictive chest wall syndrome, 928 Constrictive pericarditis, 684, 685 Contact dermatitis, 110, 164, 226–227, 294–295, 316 Contact vulvovaginitis, 1062 Contraception, 228–231. See also Oral contraceptives Contrast nephropathy, 18–19 Conversion disorder, 79 Copper accumulation, in Wilson disease, 1018–1019 Copper deficiency, 847 Copper T380 IUD, 228 Corneal abrasion, 222, 242, 243 Corneal haze, 392 Corneal opacities, in adenovirus infection, 27 Cornelia de Lange syndrome, 1045 Coronary artery, anomalous, 54–55 Coronary artery disease, 195 Coronary sinus atrial septal defect, 84 Coronavirus, 838–839 Cor pulmonale, 220, 232–233, 307, 759, 853 Corrective lenses, 773, 883 Cortical visual impairment, 364

Corticosteroids, 1070 for acute disseminated encephalomyelitis, 79 for acute lymphoblastic leukemia, 23 for acute myeloid leukemia, 25 for adrenal insufficiency, 743 for allergic child, 31 for allergic rhinitis, 799 for alopecia, 33 for altitude sickness, 37 for anaphylaxis, 49 for asthma, 76 for atopic dermatitis, 82–83 for autoimmune hemolytic anemia, 91 and avascular necrosis of femoral head, 92, 93 for Bell palsy, 100, 101 for blepharitis, 111 for brain abscess, 119 for brain tumors, 123 for bronchopulmonary dysplasia, 136 for cardiomyopathy, 153 for common variable immunodeficiency, 211 for congenital adrenal hyperplasia, 217, 743 for contact dermatitis, 227 for cough, 237 for Crohn disease, 239 for croup, 241 for dermatomyositis/polymyositis, 281 for diaper rash, 295 for Duchenne muscular dystrophy, 615 for eosinophilic esophagitis, 335 for Epstein-Barr virus infection, 341 for erythema multiforme, 343 for erythema nodosum, 345 for food allergy, 367 for food protein-induced enterocolitis syndrome, 369 for glomerulonephritis, 395 for graft-versus-host disease, 402, 403 growth deceleration with, 844 for hemolysis, 425 for hemoptysis, 433 for Henoch-Schönlein purpura, 435

for histiocytosis, 449 for histoplasmosis, 451 for Hodgkin lymphoma, 453 for hypercalcemia, 465 hypertension with, 472 for hypopituitarism, 487 for idiopathic cavernous sinusitis, 159 for immune thrombocytopenic purpura, 500–501 for infantile hemangioma, 421 for infantile spasms, 511 intracranial hypertension with, 496 for juvenile idiopathic arthritis, 64–65 for Kawasaki disease, 537 for lupus erythematosus, 557 for lymphoproliferative disorders, 565 for meconium aspiration syndrome, 581 for mediastinal mass, 583 for meningitis, 587 for morphea, 607 for myasthenia gravis, 617 for myocarditis, 619 for nephrotic syndrome, 636, 637 for neurocysticercosis, 915 for non-Hodgkin lymphoma, 647 for obstructive sleep apnea, 853 for otitis externa, 667 for peritonsillar abscess, 695 for pharyngitis, 703 for phimosis, 705 for polyarteritis nodosa, 721 for psoriasis, 753 for refractory celiac disease, 163 for rheumatic fever, 796, 797 for Rocky Mountain spotted fever, 805 for Salmonella infections, 813 for sarcoidosis, 815 for scabies, 817 for seborrheic dermatitis, 823 and sepsis, 830, 831 for septic arthritis, 835 for serum sickness, 837

for sinusitis, 851 for sore throat, 863 for systemic sclerosis, 914 for tinea capitis, 379 toxicity of, 146, 147 for transverse myelitis, 959 for ulcerative colitis, 972–973 for urticaria, 983 for wheezing, 1015 Corynebacterium diphtheriae, 300 Coryza, 132, 340, 714 Costello syndrome, 794, 1045 Costochondritis, 234–235 Cough, 236–237 Cough and cold medicines, 237 Cough etiquette, 182 Cough syncope, 701 Cowden syndrome, 728 Coxsackie virus, 152, 294, 412, 586, 702, 862, 880 Cracked nipples, 128, 129 Cradle cap, 822–823 Craniofacial dysostosis (Crouzon disease), 460, 1045 Craniopharyngioma, 122 Craniosynostosis, 460, 466 Cretinism, 495 Creutzfeldt-Jakob disease, 744–745 Crigler-Najjar syndrome, 532, 533, 1045 Crimean-Congo hemorrhagic fever, 320 “Crocodile tears,” 101 Crohn disease, 238–239, 972 cholelithiasis in, 184 gastroenteritis in, 380 intestinal obstruction in, 519 pancreatitis in, 674 perirectal abscess in, 690, 691 pseudopolyps in, 728 psoriasis with, 752 short-bowel syndrome in, 846 Croup, 240–241, 338, 577, 783 Crouzon disease, 460, 1045 Crusted scabies, 816

Crying, 242–243 in colic, 206–207, 242 in meningitis, 242, 243, 586 normal, 206 pathologic, 242 Cryotherapy, 457, 787, 1009 Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS), 245 Cryptococcal infections, 244–245, 586 Cryptogenic enteropathy-associated T-cell lymphoma, 163 Cryptorchidism, 246–247 Down syndrome and, 306 germ cell tumors with, 384 hydrocele with, 458 hypospadias with, 246, 490 inguinal hernia with, 514 pubertal delay with, 754 Wilms tumor with, 1016 Cryptosporidiosis, 248–249, 256, 257, 258, 370–371 Cupping, 178 Currarino syndrome, 506 Cushing disease, 250, 251 Cushing syndrome, 250–251, 563, 652 amenorrhea in, 44, 45 hypokalemia in, 480, 481 Cushing triad, 119, 592, 594 Cutaneous amebiasis, 43 Cutaneous anthrax, 58–59 Cutaneous aspergillosis, 70, 71 Cutaneous blastomycosis, 108 Cutaneous candidiasis, 148, 149, 378–379 Cutaneous coccidioidomycosis, 204 Cutaneous diphtheria, 300, 301 Cutaneous larva migrans, 252–253 Cutaneous warts, 1008 Cyanocobalamin, 585 Cyanosis, 132–133, 1033–1038, 1039 in brain abscess, 118 in breath-holding spells, 130 in hypoplastic left heart syndrome, 488, 489 in methemoglobinemia, 600 in pertussis, 700, 701

in Pneumocystis jiroveci infection, 714 in pneumothorax, 718 in polycythemia, 726, 727 in portal hypertension, 730 in respiratory distress syndrome, 780 in respiratory syncytial virus, 782 in tetralogy of Fallot, 924, 925 in tracheitis, 942 in transposition of great arteries, 956 in ventricular septic defect, 994, 995 Cyclic neutropenia, 644–645, 1045 Cyclic vomiting syndrome (CVS), 254–255, 416, 1004 Cyclospora, 256–257 Cysticercosis, 118, 119, 914–915 Cystic fibrosis (CF), 258–259 aspergillosis in, 70, 258, 259 atelectasis in, 80, 258, 259 bezoars in, 102 chest pain in, 172 Chlamydophila pneumoniae in, 183 cholelithiasis in, 184, 185 cholestasis in, 632 chronic hepatitis in, 192 cirrhosis in, 196, 197, 258 cor pulmonale in, 232 cough in, 236–237 diarrhea in, 188, 189, 258, 298, 299, 376 feeding disorders in, 354 gastroesophageal reflux in, 382 giardiasis in, 388 hemoptysis in, 432 hepatomegaly in, 258, 436 hypokalemia in, 480 hyponatremia in, 482 inguinal hernia in, 514 intestinal obstruction in, 518 malabsorption in, 258, 566–567 nasal and lung symptoms in, 30, 258 pneumonia in, 716 pneumothorax in, 259, 718 rectal prolapse in, 258, 259, 770–771

short-bowel syndrome in, 846 wheezing in, 258, 1014 Cystic hygroma, 622 Cystic nephroma, 2 Cystinosis, 194, 776, 777, 1045 Cystinuria, 316, 981, 1046 Cystitis, 978–979 in adenovirus infection, 26–27 in cancer therapy, 146 in candidiasis, 149 dysuria in, 316 hemorrhagic, 422, 423 Cystoisospora belli, 256, 257 Cytomegalovirus (CMV), 260–261 Bell palsy with, 100 blood transfusion and, 949 in bone marrow transplantation, 112 cholestasis with, 632 congenital/postnatal, 364 developmental delay in, 282 fever of unknown origin with, 360, 361 gastritis with, 380 hepatitis with, 260, 1000 hepatomegaly with, 260, 436, 437 hereditary spherocytosis with, 441 in HIV, 455 hydrocephalus with, 460 parotitis in, 610 D Dacryocystitis, 540, 541 Dacryocystocele, 540, 541 Dactylitis, in sickle cell disease, 848, 849 Dandy-Walker malformation, 78, 460 Darier disease, 32, 707 Day care, return to. See Return to school or day care Daytime incontinence, 106, 262–263, 332 Daytime sleepiness, excessive, 620–621, 852 Deafness. See also Hearing loss autism spectrum disorder vs., 88 in immune deficiency, 499 in renal tubular acidosis, 777

stereotypic movement disorder in, 414 Decompensated cirrhosis, 196 Decongestants, 99, 223, 513, 799 Deep venous thrombosis (DVT), 930–931, 959 Dehydration, 264–265, 1059 crying in, 243 in diabetes insipidus, 286–287, 487 in diabetic ketoacidosis, 292–293 in diarrhea, 264–265, 298, 299 in Epstein-Barr virus infection, 341 in food allergy, 366 in food poisoning, 370–371 in hand, foot, and mouth disease, 413 in polycythemia, 726, 727 portal vein obstruction in, 160 in pyloric stenosis, 764, 765 in respiratory syncytial virus, 783 in Reye syndrome, 790 in rotavirus infection, 808–809 in Salmonella infections, 812, 813 in short-bowel syndrome, 847 in vomiting, 264–265, 1005 weight loss in, 1011 Delayed cord clamping, 427 Delayed hemolytic transfusion reaction (DHTR), 948–949 Delayed puberty, 754–755, 844–845 Delirium, 208 Delorme procedure, 771 Dementia, in megaloblastic anemia, 585 De Morsier syndrome, 486 Dengue fever, 269, 361 Dengue hemorrhagic fever, 269 Dengue shock syndrome, 269 Dengue virus, 268–269 Dental abscess, 46, 274–275, 318, 319, 484, 485, 800 Dental care, in hemophilia, 431 Dental caries, 266, 270–273 Dental health, 272–273 Dental infections, 274–275, 318, 319 Dental procedures, endocarditis prophylaxis in, 330, 924–925 Dental sealants, 273

Dental trauma, 276–277, 319 Dent disease, 776 Dentition, 916–917, 1057 Dent syndrome, 1046 Denys-Drash syndrome, 2, 384, 636, 746, 1016 Depot-medroxyprogesterone acetate (DMPA), 228, 313 Depression, 278–279, 288 in acne, 12, 14, 15 in cancer therapy, 147 in child abuse, 178 in cystic fibrosis, 259 in eating disorders, 56, 57, 142, 278 in epilepsy, 824 in megaloblastic anemia, 585 in obesity, 652, 653 in obsessive-compulsive disorder, 654 in polycystic ovarian syndrome, 724 in premenstrual syndrome, 740 separation anxiety disorder with, 828 in sexual abuse, 843 in social anxiety disorder, 860 in stuttering, 889 in transgender youth, 950 weight loss in, 1010 Deprivation amblyopia, 40, 155, 772 Dermal sinus tracts, 638 Dermal vascular thrombosis, 760–761 Dermatitis allergic, 110, 226, 227, 294, 748 atopic (See Atopic dermatitis) candidal, 226, 294–295 contact, 110, 164, 226–227, 294–295, 316 diaper, 148, 294–295, 316, 333 in hereditary spherocytosis, 441 in hyperimmunoglobulinemia E syndrome, 466–467 in sarcoidosis, 814 seborrheic, 110, 226, 294, 822–823 Dermatographism, 30, 748, 982 Dermatologic toxicity, in cancer therapy, 146 Dermatomyositis, 280–281 Dermatophyte infections, 378–379

Dermoid cyst, 622 De Sanctis-Cacchione syndrome, 1046 “Designer” opioids, 659 Developmental coordination disorder, 546 Developmental delay, 282–283 feeding disorders in, 354 with floppy infant syndrome, 362 with fragile X syndrome, 372 with intellectual disability, 283, 516, 517 language or speech problems with, 282, 283, 866, 867 with neonatal cholestasis, 633 with obesity, 653 with persistent pulmonary hypertension of newborn, 696 with renal tubular acidosis, 777 with retinoblastoma, 785 with 22q11.2 deletion syndrome, 266 with West syndrome, 510 Developmental disabilities, 1055 Developmental dysplasia of hip (DDH), 284–285, 520, 521, 638 Developmental language disorder (DLD), 283, 864 Developmental milestones, 1055 Developmental venous anomalies (DVAs), 992–993 Dexamethasone test, 250 Diabetes insipidus, 286–287, 332, 448, 449, 486–487 Diabetes mellitus alopecia in, 32, 33, 288 cancer therapy and, 146 candidiasis in, 148, 288 cataracts in, 154 celiac disease in, 162 chest pain in, 172 enuresis in, 332 hepatomegaly in, 436 hyperlipidemia in, 471 hypertension in, 472, 473 hypothyroidism in, 492 immunoglobulin A deficiency with, 502 maternal, and neonatal hypoglycemia, 596 and neural tube defects, 638 nontuberculous mycobacterial infections in, 648 obesity in, 652, 653

perirectal abscess with, 690, 691 in polycystic ovarian syndrome, 725 thrombosis in, 930 tuberculosis with, 964 type 1, 288–289 type 2, 290–291, 598–599 urolithiasis and, 980 weight loss in, 1010 Diabetic ketoacidosis (DKA), 264, 288, 289, 290, 292–293, 1004 Diabetic nephropathy, 288, 289, 291 Diabetic neuropathy, 288, 289, 291 Diabetic retinopathy, 288, 291 Diabetic vasculopathy, 288, 289 Dialysis for acute kidney injury, 19 for Ebola virus infection, 321 for hemolytic uremic syndrome, 429 for hypercalcemia, 465 for hypertension, 473 for rhabdomyolysis, 793 for salicylate poisoning, 811 for toxic alcohol poisoning, 937 Diamond-Blackfan syndrome, 22, 584, 670, 953, 1046 Diaper rash, 148, 294–295, 316, 333, 840 Diaphragmatic hernia, 80, 237, 296–297, 382, 696, 928, 1002 Diarrhea, 298–299 acute, 188, 298 in adenovirus infection, 26–27 antibiotic-associated, 298, 299 in Campylobacter infection, 144–145 in cholera, 186–187 chronic, 188–189, 298 congenital chloride, 480 in cryptosporidiosis, 248–249 in Cyclospora infection, 256–257 in cystic fibrosis, 188, 189, 258, 298, 299 dehydration in, 264–265, 298, 299 in food poisoning, 370–371 functional, of infancy, 376–377 in gastritis, 380 in giardiasis, 388–389

hypokalemia in, 480, 481 hyponatremia in, 482 in irritable bowel syndrome, 530–531 in lactose intolerance, 542–543 in malabsorption, 566–567 in megaloblastic anemia, 584 osmotic, 188, 298 persistent, 298 rectal prolapse with, 770 in rotavirus infection, 808–809 secretory, 188, 298 in short-bowel syndrome, 846, 847 Diastematomyelia, 638–639 DIC. See Disseminated intravascular coagulation Diet in alcohol intoxication, 29 in anorexia nervosa, 56, 57 in aplastic anemia, 61 in ascites, 69 in asthma, 76–77 in avascular necrosis of femoral head, 93 in biliary atresia, 105 in bladder and bowel dysfunction, 107 in breastfeeding, 129 in Campylobacter infection, 144 in celiac disease, 162, 163 in cerebral palsy, 167 in cholelithiasis, 184, 185 in cholera, 187 in chronic kidney disease, 195 in cirrhosis, 197 in cleft lip and palate, 199 in colic, 207 in constipation, 224, 225 in contact dermatitis, 227 in cystic fibrosis, 259 and dental caries, 270, 271 in diabetes mellitus type 1, 289 in diabetes mellitus type 2, 291 in diarrhea, 299 in dysmenorrhea, 313

in Ebola virus disease, 321 in edema, 323 elimination, 367 in encopresis, 329 in eosinophilic esophagitis, 335 in failure to thrive, 352–353 in feeding disorders, 355 in food allergy, 366–367 in food hypersensitivity, 368–369 in functional diarrhea of infancy, 376, 377 in fungal skin infections, 379 in G6PD deficiency, 397, 425 in gastritis, 381 in gastroesophageal reflux disease, 383 in gingivitis, 391 in glomerulonephritis, 395 in hemolysis, 425 in histiocytosis, 449 in hyperlipidemia, 470, 471 in hypertension, 473 in hypoglycemia, 479, 596 in hypokalemia, 481 in hyponatremia, 483 in hypothyroidism, 495 in iron deficiency anemia, 527 in irritable bowel syndrome, 531 ketogenic, 511, 825 in lactose intolerance, 543 in lead poisoning, 545 in liver failure, 21 in lower GI bleeding, 555 in lymphedema, 563 in megaloblastic anemia, 584 in metabolic syndrome, 599 in microcytic anemia, 602 in necrotizing enterocolitis, 625 in neonatal abstinence syndrome, 627 in neonatal cholestasis, 633 in neonatal sepsis, 833 in nephrotic syndrome, 637 in NICU graduates, 365

in obesity, 653 in peritonitis, 693 in pleural effusion, 713 in polyarteritis nodosa, 721 in polycystic kidney disease, 723 in portal hypertension, 731 in purpura fulminans, 761 in rectal prolapse, 771 in renal artery stenosis, 775 in respiratory distress syndrome, 780 in short-bowel syndrome, 847 in SIADH, 907 in slipped capital femoral epiphysis, 855 in spondyloarthropathy, 873 in tracheitis, 943 in transient tachypnea of newborn, 955 in transverse myelitis, 959 in trichinosis, 961 in Wilson disease, 1019 Diffuse large B-cell lymphoma (DLBCL), 646–647 Diffuse mesangial sclerosis (DMS), 636 DiGeorge syndrome. See 22q11.2 deletion syndrome Digital clubbing, 258 Dilated cardiomyopathy (DCM), 26, 27, 152–153, 220, 996 Diphtheria, 300–301 tetanus, and pertussis vaccines, 300, 301, 700, 843, 922, 984–985 Diphtheria antitoxin, 301 Diphyllobothrium latum, 914 Dipylidium caninum, 914 Direct observation, 1029 Disc herniation, 96, 97, 820 Disease-modifying antirheumatic drugs (DMARDs), 65 Disimpaction, 225, 329 Diskitis, 96, 97, 302–303 Disorders of sexual development (DSD), 38–39, 217, 246 Disruptive mood dysregulation disorder, 278 Disseminated anthrax, 58, 59 Disseminated blastomycosis, 108 Disseminated candidiasis, 148, 149 Disseminated coccidioidomycosis, 204, 205 Disseminated herpes simplex infection, 442, 443

Disseminated intravascular coagulation (DIC), 304–305 bruising in, 138, 139 diabetes ketoacidosis and, 293 Ebola virus and, 321 in enteric fever, 813 hemolysis in, 424, 425 in histoplasmosis, 450 measles and, 577 meningococcemia and, 588, 589 necrotizing enterocolitis and, 304, 624, 625 petechiae in, 358 in purpura fulminans, 304, 760–761 in rickettsial disease, 803, 805 in sepsis, 831, 832 in toxic shock syndrome, 939 Diuretics abuse of, 142 for aortic coarctation, 202 for ascites, 69 for bronchopulmonary dysplasia, 137 for cardiomyopathy, 153 for congestive heart failure, 85, 221 for cor pulmonale, 233 for diabetes insipidus, 287, 487 for edema, 323 for glomerulonephritis, 395 for hydrocephalus, 461 for hypercalcemia, 465 for hypertension, 473, 599 hypokalemia with, 480 for hypoplastic left heart syndrome, 489 for idiopathic intracranial hypertension, 497 for lymphedema, 563 for myocarditis, 619 for nephrotic syndrome, 637 for polycystic kidney disease, 723 for portal hypertension, 731 for renal artery stenosis, 775 in renal tubular acidosis, 776, 777 for rhabdomyolysis, 793 for sarcoidosis, 815

for transfusion reaction, 949 DKA. See Diabetic ketoacidosis Dog bites, 572–573, 766–767 Dog tapeworm, 914–915 Down syndrome, 306–307 autoimmune thyroiditis in, 492 blepharitis in, 110 cataracts in, 154, 306, 307 celiac disease in, 162, 306, 307 cor pulmonale in, 232, 307 developmental delay in, 282 diaphragmatic hernia in, 296 esophageal atresia/TEF in, 944 glaucoma in, 307, 392 Graves disease in, 404 Hirschsprung disease in, 406 hydrocephalus in, 460 hypercalcemia, 464 hypotonia in, 363 imperforate anus in, 506 infantile spasms in, 510 intellectual disability in, 306, 307, 516 intestinal obstruction in, 518 lacrimal duct obstruction in, 540 leukemia in, 22, 306 leukocytosis in, 548 lymphedema in, 562 obstructive apnea in, 306, 852 patent ductus arteriosus in, 306, 678 persistent pulmonary hypertension of newborn in, 696 refractive errors in, 772 short stature in, 845 stereotypic movement disorder in, 414 tetralogy of Fallot in, 924 tooth eruption in, 917 transient myeloproliferative disorder in, 468 Dravet syndrome, 876 Drowning, 308–309 Drug fever, 360 Drug-induced interstitial nephritis, 422 Drug-induced liver injury (DILI), 192

Drug withdrawal, acute, 16–17 crying in, 243 neonatal abstinence syndrome in, 16–17, 364, 626–627 opioid, 16–17, 626–627, 658, 659 Dry cough, 236 Dry eye, 110 Dry heaves, 1004 Duane syndrome, 883 Dubin-Johnson syndrome, 1046 Dubowitz syndrome, 1046 Duchenne muscular dystrophy, 80, 232, 614–615 Duct tape, for warts, 1009 Duke criteria, modified, 331 Dumping syndrome, 383, 980 Duncan disease, 340 Duodenal atresia, 506, 518 Duodenal obstruction, 519 DVT. See Deep venous thrombosis Dwarfism, 844, 845 Dysentery, 370 Dyserythropoietic anemias, 602 Dysfibrinogenemia, 8 Dysfunctional uterine bleeding, 310–311 Dyskeratosis congenita, 1046 Dyskinetic cerebral palsy, 166 Dysmenorrhea, 312–313 Dysphagia with eosinophilic esophagitis, 334 with esophageal atresia/TEF, 945 feeding disorders in, 354–355 with food allergy, 366 with gastroesophageal reflux disease, 382, 383 pharyngeal, 354, 355 with retropharyngeal abscess, 788 with 22q11.2 deletion syndrome, 266, 267 Dyspnea, 314–315 in pericarditis, 684 in pleural effusion, 712 in pneumothorax, 718 in polycythemia, 726 in pulmonary hypertension, 758

in severe acute respiratory syndrome, 839 in tuberous sclerosis, 966 Dysthymic disorder, 278–279 Dystonia, 934 Dystrophinopathies, 614–615 Dysuria, 316–317, 762, 988 E Eagle-Barrett (prune belly) syndrome, 192, 246, 462, 514, 976, 1051 Earache, 318–319, 668–669 Ear infection. See Otitis externa; Otitis media Early childhood caries (ECC), 270–273 Early-onset sepsis (EOS), 832, 833 Ear pain, barotrauma and, 98–99, 318 Eastern equine encephalitis, 1012, 1013 Eating disorder anorexia nervosa as, 56–57 bulimia as, 142–143 depression in, 56, 57, 142, 278 hypokalemia in, 480, 481 mortality rate in, 143 rectal prolapse in, 770 sexual abuse and, 142 substance use disorders with, 892 transgender youth and, 950 trichotillomania with, 962 weight loss in, 1010 Ebola virus disease (EVD), 320–321 Ebstein anomaly, 1041 Ecchymoses, 138 Echinococcosis, 914–915 Echocardiography, 1041 Echovirus, 16, 412 Eclampsia, 304, 424 Ecthyma, 508 Ectodermal dysplasia, 32, 498, 1046 Ectopic kidney, 506 Ectopic pregnancy, 3, 169, 681 Ectopic ureter, 462, 463, 998 Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, 198, 1046 Eczema herpeticum, 82, 83, 442, 443, 881 Edema, 322–323. See also specific types

Edrophonium chloride test, 617 Edwards syndrome. See Trisomy 18 Ehlers-Danlos syndrome, 284, 514, 770, 772, 886, 1046 Ehrlichiosis, 95, 324–325, 327, 360, 361, 802–803 Eisenmenger syndrome, 994, 995 Electrocardiography (ECG), 1038–1040 Elimination diet, 367 Elliptocytosis, hereditary, 440 Ellis-van Creveld syndrome, 928 Embryonal carcinomas, 384–385 Emergency contraception, 228, 231, 843 Emery-Dreifuss muscular dystrophy, 614–615 Emmetropia, 772, 1056 Emotional abuse, 178 Emotionally provoked breath-holding spells, 130–131 Emphysema, 80, 701, 718, 781 Empty sella syndrome, 486 Empyema, 46, 717 Enamel hypoplasia, 266 Encephalitis, 326–327 arbovirus, 1012–1013 cat-scratch disease, 157 cysticercal, 915 cytomegalovirus, 260 herpes simplex, 326, 327, 442, 443, 523, 881 infantile spasms with, 510 measles, 326, 577 mumps, 326, 611 rabies, 766–767 roseola, 807 rotavirus, 809 rubella, 387 Salmonella, 812 tick fever, 933 toxoplasmosis, 940, 941 tularemia, 969 varicella, 174, 175, 326 Encephalocele, 638–639 Encephalomalacia, 364 Encephalopathy bilirubin, 426, 427, 535

cat-scratch disease, 157 epileptic, 510 glycine, 1047 hepatic (See Hepatic encephalopathy) hyperammonemia, 594 hypoxic-ischemic, 120, 364–365, 510, 634–635, 696, 697 lead, 544, 545 metabolic acidosis, 592 neonatal, 634–635 peritonitis, 692, 693 Reye syndrome, 790–791 toxic shock syndrome, 939 transmissible spongiform, 744–745 Enchondromatosis, 664 Encopresis, 225, 298, 328–329, 332 Endemic typhus, 802 Endocarditis, 330–331 candidiasis, 148 cat-scratch disease, 157 fever and petechiae in, 358 fever of unknown origin in, 360, 361 gonococcal, 401 intracranial hemorrhage in, 522, 523 in lupus erythematosus, 557 prophylaxis, 85, 330, 331, 924–925, 995 rickettsial disease and, 803 tetralogy of Fallot and, 924–925 ventricular septal defect and, 995 Endocrine toxicity, in cancer therapy, 146 Endometrial cancer, 725 Endometriosis, 312, 724 Endometritis, 680. See also Pelvic inflammatory disease Endophthalmitis, 148 Enema, 225, 525, 972, 973 Engraftment syndrome, 113 Entamoeba histolytica, 42–43, 370–371 Enteral nutrition therapy for Crohn disease, 239 and necrotizing enterocolitis, 624 for short-bowel syndrome, 847 Enteric fever, 812–813

Enteritis. See also Gastroenteritis in Campylobacter infections, 144–145 methemoglobinemia associated with, 600–601 Enterobius gregorii, 708 Enterobius vermicularis, 708 Enterocolitis food protein-induced, 366–369 in Hirschsprung disease, 446–447 necrotizing (See Necrotizing enterocolitis) Yersinia, 370–371, 1022–1023, 1063 Enteroviral infection fever and petechiae in, 358 hand, foot, and mouth disease with, 412 hepatitis in, 1000 meningitis with, 587 parotitis in, 610 stomatitis in, 880, 881 Enthesitis-related arthritis (ERA), 64, 872–873 Enuresis, 106, 262, 328, 332–333 Enzyme therapy for α1-antitrypsin deficiency, 35 for chronic diarrhea, 189 for cystic fibrosis, 259, 771 for lactose intolerance, 543 Eosinophilic esophagitis (EoE), 334–335, 366–367, 382, 1010 Eosinophilic gastroenteritis, 366–367, 380 Ependymoma, 122–123 Epidemic keratoconjunctivitis, 26–27 Epidemic typhus, 802 Epidermal inclusion cysts, 682, 683 Epidermolysis bullosa, 1046 Epidermolysis bullosa dystrophica, autosomal dominant, 1046 Epididymitis, 180, 336–337, 400, 401, 422, 423, 921 Epididymo-orchitis, 458, 459, 610, 921 Epidural abscess, 46, 851 Epidural hematoma, 522, 890 Epigastric pain, 6 Epiglottitis, 240, 338–339, 694, 862, 863 Epilepsy, 824–825 autism spectrum disorder and, 88, 89 breath-holding spells and, 130

febrile infection-related, 326, 826 febrile seizures and, 826, 827 status epilepticus in, 876–877 stroke and, 887 subdural hematoma and, 891 syncope in, 904 Epileptic ataxia, 79 Epileptic encephalopathy, 510 Epileptic spasm, 510–511 Epinephrine for anaphylaxis, 49, 367, 949 for croup, 241 for food protein-induced enterocolitis syndrome, 369 for myocarditis, 619 for nosebleeds, 650 for sepsis, 831 for wheezing, 1015 Epiphora, 540 Episcleritis, 222, 238 Episodic ataxias, 78, 79 Epispadias, 350–351, 514 Epistaxis, 431, 650–651 Epstein-Barr virus (EBV), 260, 340–341 Bell palsy with, 100, 340 encephalitis with, 326 fever and petechiae with, 358 fever of unknown origin with, 360, 361 hepatitis with, 340, 1000 hepatomegaly with, 340, 436, 437 hereditary spherocytosis with, 441 Hodgkin lymphoma with, 452 lymphoproliferative disorder with, 564–565 neck masses with, 622, 623 parotitis with, 610 pharyngitis with, 702, 703 Wiskott-Aldrich syndrome with, 1021 Erb palsy, 116–117 Erdheim-Chester disease, 448 Erythema infectiosum, 676–677 Erythema marginatum, 796 Erythema migrans, 164, 558

Erythema multiforme, 342–343, 442, 836, 878, 969 Erythema nodosum, 164, 344–345 in cat-scratch disease, 157 in Crohn disease, 238 in histoplasmosis, 450, 451 in sarcoidosis, 344, 345, 814 in tularemia, 969 in Yersinia enterocolitica infection, 1023 Erythema toxicum, 604 Erythroblastopenia, transient of childhood, 952–953 Erythroblastosis fetalis, 304 Erythrodermic psoriasis, 752, 753 Erythropoietin, 51, 427, 635 Escherichia coli in breast abscess, 126 in fever of unknown origin, 360 in food poisoning, 370–371, 1063 in hemolytic uremic syndrome, 428–429 in neonatal sepsis, 832 in omphalitis, 656 in pelvic inflammatory disease, 680 in peritonitis, 692 in urinary tract infection, 978, 979 Esophageal atresia, 383, 506, 578, 764, 944–945 Esophageal foreign body, 863 Esophageal leak, 945 Esophageal perforation, 335 Esophageal rupture, 335 Esophageal strictures, 146, 335, 945 Esophageal varices in chronic hepatitis, 193 in cirrhosis, 197 in cystic fibrosis, 259 in portal hypertension, 730–731 in upper GI bleeding, 974–975 Esophagitis candidal, 148, 149, 455, 863 chest pain in, 172, 173 earache in, 319 eosinophilic, 366–367, 382, 1010 reflux, 382

Esotropia, 772, 773, 882, 883 Estrogen-progestin contraceptives, 228, 229, 230 Ethanol intoxication, 28–29 Ethylene glycol, 936–937 Etonogestrel implant, 228, 230, 231, 313 Eustachian tube dysfunction, 318, 319, 668 Euvolemic hyponatremia, 482 Evisceration, 657 Ewing sarcoma, 96, 346–347, 665 Excessive daytime sleepiness, 620–621, 852 Excoriation disorder, 348–349 Executive function, 365, 546, 638 Exercise in anorexia nervosa, 56 for anterior knee pain, 539 for back pain, 97 in bulimia, 142 in cholelithiasis, 184 for dysmenorrhea, 313 for metabolic syndrome, 599 for premenstrual syndrome, 741 Exertional heat stroke, 418 Exophthalmos, 404, 578 Exotic ungulate encephalopathy, 744 Exotropia, 882 Expiratory grunting, 242, 780 Expressive language disorders, 864, 866 Exstrophy-epispadias complex, 350–351 Extracorporeal membrane oxygenation (ECMO), 153, 221, 297, 581, 697 Eyelid inflammation, 110–111 F Fabry disease, 154, 562, 886, 1046 Facial nerve (Bell) palsy, 100–101, 319, 340, 575, 611 Facioscapulohumeral muscular dystrophy, 614–615 Factitious fever, 360 Factor V Leiden deficiency, 756 Factor VIII deficiency, 430–431 Factor VIII replacement, 431, 1007 Factor IX deficiency, 430–431 Factor IX replacement, 431 Factor VII/Factor VIIa, 21, 305, 523

Factor XIII deficiency, 8 Failure to thrive (FTT), 352–353 with cystic fibrosis, 258 with diaphragmatic hernia, 297 with eosinophilic esophagitis, 334 with feeding disorders, 354 with fetal alcohol syndrome, 357 with food allergy, 366 with gastroesophageal reflux disease, 382 with giardiasis, 389 with immune deficiency, 498 with malabsorption syndromes, 566 with necrotizing enterocolitis, 625 with neonatal cholestasis, 633 with obstructive sleep apnea, 853 with patent ductus arteriosus, 679 with posterior urethral valves, 732 with renal tubular acidosis, 777 with rickets/osteomalacia, 801 with severe combined immunodeficiency, 840 with short-bowel syndrome, 847 short stature in, 844 with thalassemia, 926 with tuberculosis, 964 with 22q11.2 deletion syndrome, 266 with ventricular septic defect, 994 Familial adenomatous polyposis (FAP), 728, 729, 1046 Familial combined hyperlipidemia (FCHL), 470, 471 Familial dysautonomia, 446, 1046 Familial hematuria, 422, 423 Familial hemophagocytic lymphohistiocytosis, 498, 499 Familial hypercholesterolemia (FH), 470, 471 Familial hypertriglyceridemia (FHTG), 470 Familial hypocalciuric hypocalcemia (FHH), 464, 465 Familial macrocephaly, 461 Familial Mediterranean fever, 336, 360, 1046 Fanconi anemia, 22, 138, 545, 670, 1046 Fanconi-Bickel syndrome, 596, 776 Fanconi syndrome, 776, 777, 1019 Farber lipogranulomatosis, 1046 Far-sightedness (hyperopia), 372, 772–773, 882, 970, 1056

Fatal familial insomnia (FFI) syndrome, 744 Fatty acid deficiency, 847 Fatty acid oxidation defects, 20, 363, 478, 532, 592, 594–595, 597 Fatty liver of pregnancy, 592 Fava beans (favism), 396, 397, 424 Fazio-Londe disease, 868 Febrile infection-related epilepsy syndrome (FIRES), 326, 826 Febrile nonhemolytic transfusion reaction (FNHTR), 948–949 Febrile seizures, 826–827 Febrile status epilepticus, 826, 827 Fecal incontinence, 147, 298, 328–329, 447, 507 Fecalith, 62 Feedback, 1030 Feeding disorders, 354–355, 365, 367 Feingold syndrome, 944 Feline spongiform encephalopathy, 744 Female athlete triad, 56 Femoral anteversion, 520–521, 538 Femoral artery thrombosis, 930 Femoral head avascular necrosis of, 92–93, 835, 848, 849, 855 displacement of, 92, 487, 652, 653, 854–855 osteonecrosis of unknown origin, 698–699 Femoroacetabular impingement, 855 Fenugreek, 129, 313 Fetal alcohol syndrome (FAS), 154, 282, 356–357, 516, 924 Fetal brain disruption sequence (FBDS), 1024, 1046 Fetal hiccups, 444 Fetal hydantoin syndrome, 1046 Fetal rubella syndrome, 1046 Fetal valproate syndrome, 1046 Fetal warfarin syndrome, 1046 Fetomaternal hemorrhage, 426, 427 Fetus, retained, 304 Fetus in fetu, 2 Fever and petechiae, 358–359 Feverfew, 417 Fever of unknown origin (FUO), 360–361, 940 Fibrodysplasia ossificans progressiva (FOP), 1046 Fibroma, 966 Fibromuscular dysplasia (FMD), 774

Fibromyalgia, 96 Fibrosarcoma, 2 Fibrous dysplasia, 664 Fifth disease, 676–677 Filariasis, 322 Filariform larvae, 252 Fire ant bites, 858 Fish oil, 313, 505, 847 Fish tapeworm, 914–915 Fistula-in-ano, 690, 691 Fitz-Hugh-Curtis syndrome, 400, 401, 436 5α-reductase deficiency, 1044 Fixed drug reaction, 226 Flail, 116 Flail chest syndrome, 928 Flat warts, 1008 Floppy infant syndrome, 362–363 Fluency disorders, 866, 888–889 Fluoride, 272–273, 390 Focal cortical dysplasia, 510 Focal dermal hyperplasia, 32, 1046 Focal segmental glomerulosclerosis (FSGS), 194, 195, 636–637 Focal seizures, 824, 825 FODMAP diet, 531, 566 Folic acid for hereditary spherocytosis, 441 for megaloblastic anemia, 585 for pregnant women or women planning pregnancy, 638, 639 for thalassemia, 927 for toxic alcohol poisoning, 937 for transient erythroblastopenia of childhood, 953 Folic acid (folate) deficiency, 441, 584–585, 638–639, 847 Follow-up of NICU graduates, 364–365 Fontanel, bulging, 242, 243, 592, 594, 830 Fontan procedure, 488, 489 Food allergy, 30–31, 48, 366–367 atopic dermatitis and, 83 dysuria in, 316 eosinophilic esophagitis in, 334–335, 366–367 gastroesophageal reflux in, 366, 367, 382 Foodborne botulism, 114–115

Foodborne illness, 370–371, 1063 Food challenges, 367 Food hypersensitivity, 368–369 Food impaction, 335, 366, 367 Food-induced asthma, 76 Food intolerance, 30 Food poisoning, 370–371, 812–813, 1063 Food protein-induced allergic proctocolitis, 366, 368–369 Food protein-induced enterocolitis syndrome (FPIES), 366–369 Food protein-induced enteropathy, 366, 368–369 Foreign body in ear, 318, 319 in esophagus, 863 in urinary tract, 316, 317 in vaginitis, 988, 1062 Foreign body aspiration, 30, 80–81, 236–237, 240, 432, 1014, 1015 Foreign body ingestion, 172 Foreign material in GI tract (bezoars), 102–103, 518 Foreskin problems, 682–683, 704–705 4p syndrome, 678, 1044 Fractures child abuse and, 178–179 crying in, 242, 243 dental, 276–277 mandibular, 276, 277 maxilla, 276 osteogenesis imperfecta and, 660–661 pathologic, 663 in rickets/osteomalacia, 800, 801 Fragile X-associated tremor/ataxia syndrome (FXTAS), 372 Fragile XE syndrome (FRAXE), 372, 1047 Fragile X syndrome, 88, 282, 372–373, 506, 516, 864, 1046 Francisella tularensis, 968. See also Tularemia Frasier syndrome, 384, 636 Friedreich ataxia, 78, 1047 Frostbite, 374–375 Frostnip, 374, 375 Fructose intolerance, 532, 592, 597, 776, 1047 Fukuyama muscular dystrophy, 1047 Fulminant hepatitis, 304, 1001 Functional diarrhea of infancy, 376–377

Fungal infections. See also specific infections in bone marrow/stem cell transplantation, 112–113 encephalitis, 326 meningitis, 586–587 skin, 378–379 Funisitis, 656 Furunculosis, 318 Fusobacterium, 46 G Galactorrhea, 44, 45, 754 Galactose-α-1,3 galactose allergy, 366, 367 Galactosemia, 592, 597, 1047 acute liver failure with, 20 cataracts with, 154 jaundice with, 532, 533 neonatal cholestasis with, 632, 633 renal tubular acidosis with, 776 Galeazzi sign, 284 Gallbladder hydrops, 2, 537 Gallbladder inflammation. See Cholecystitis Gallbladder mass, 2–3 Gallbladder perforation, 185 Galloway-Mowat syndrome, 636 Gallstones. See Cholelithiasis Gamma-hydroxybutyrate withdrawal, 16 Gardner syndrome. See Familial adenomatous polyposis Gastric anal vascular ectasia (GAVE), 913 Gastric mass, 2–3 Gastrinoma, 2 Gastritis, 380–381 Gastroenteritis, 370, 371 appendicitis vs., 62 bacterial, 256 Campylobacter, 144–145 cryptosporidiosis and, 248–249 Cyclospora infection and, 257 eosinophilic, 366–367, 380 food poisoning and, 370–371 rotavirus, 808–809 Salmonella, 812–813 viral, 256

Gastroesophageal reflux, 382–383 Gastroesophageal reflux disease (GERD), 380, 382–383 apnea in, 630, 631, 852, 853 cough in, 236 crying in, 242 diaphragmatic hernia and, 297, 382 earache in, 318 eosinophilic esophagitis and, 334 in esophageal atresia/TEF, 944, 945 feeding disorders in, 354, 355 food allergy and, 366, 367, 382 fragile X syndrome and, 372, 373 in 22q11.2 deletion syndrome, 266, 267 upper GI bleeding in, 974 Gastrointestinal anthrax, 58–59 Gastrointestinal atresia, 306 Gastrointestinal bleeding lower, 554–555 upper, 974–975 Gastrointestinal food hypersensitivity, 368–369 Gastrointestinal toxicity, in cancer therapy, 146–147 Gastroparesis, 354, 382, 383 Gastroschisis, 2, 514, 846, 847 Gaucher disease, 2, 92, 1047 Gender-affirming surgery, 951 Gender assignment, 39 Gender dysphoria, 950–951 Generalized anxiety disorder, 828, 860 Generalized seizures, 824–825 Gene therapy for chronic granulomatous disease, 191 for muscular dystrophy, 615 for severe combined immunodeficiency, 840 for Wiskott-Aldrich syndrome, 1021 Genital candidiasis, 148, 149 Genital herpes, 442, 443, 843 Genitalia ambiguous, 38–39, 216, 217, 743, 746 penile and foreskin problems, 682–683, 704–705 Genital ulcers, 170–171, 340 Genital warts, 456–457, 843, 1008

Genu valgus, 538 German measles, 386–387. See also Rubella Germ cell tumors (GCTs), 2–3, 122–123, 306, 384–385 Germinoma, 384–385 Gerstmann-Sträussler-Scheinker syndrome, 744 Gestational alloimmune liver disease, 20 Giant cell myocarditis, 618, 619 Giardia duodenalis, 388 Giardia intestinalis, 388 Giardia lamblia, 388 Giardiasis, 256, 370–371, 388–389 fever of unknown origin in, 360, 361 immunoglobulin A deficiency with, 502 malabsorption in, 388, 389, 566–567 Giggle incontinence, 262 Gilbert syndrome, 532, 534, 535, 1047 Ginger, 313 Gingivectomy, 391 Gingivitis, 46, 390–391 Gingivostomatitis, 390, 412, 442, 880–881 Gitelman syndrome, 480, 481, 482 Glandular tularemia, 968 Glanzmann thrombasthenia, 1047 Glasgow coma scale (GCS), 120, 208, 308, 1061 Glasses (corrective lenses), 773, 883 Glaucoma congenital, 222, 392–393 in Down syndrome, 307, 392 myopia with, 772 retinopathy of prematurity and, 787 Glenn procedure, 488, 489 Glioma, 122–123 Glomerular proteinuria, 746 Glomerulonephritis, 18, 194, 394–395 edema in, 322 hematuria in, 394, 395, 422–423 in Henoch-Schönlein purpura, 434 in lupus erythematosus, 556 postinfectious, 394–395, 422, 423, 509, 746, 819 primary immune complex-mediated, 504–505 proteinuria in, 394, 395, 746, 747

serum sickness and, 837 splenic function in, 72 Yersinia enterocolitica infection and, 1023 Glossitis, 353, 526, 584, 602, 670, 914 Glucocorticoids for ACTH deficiency, 487 for acute lymphoblastic leukemia, 23 for anaphylaxis, 49 for congenital adrenal hyperplasia, 217 and Cushing syndrome, 250 for Henoch-Schönlein purpura, 435 for hypercalcemia, 465 for immunoglobulin A nephropathy, 505 for juvenile idiopathic arthritis, 64–65 and short stature, 844, 845 Gluconeogenesis defect, 592, 597 Glucose-6-phosphate dehydrogenase (G6PD) deficiency, 396–397 hemolysis in, 424, 425 jaundice in, 532, 533, 534, 535 pallor in, 670 rickettsial disease in, 803, 804, 805 Glucose management in type 1 diabetes mellitus, 288–289 in type 2 diabetes mellitus, 290–291 Glucose metabolism. See also Hyperglycemia; Hypoglycemia cancer therapy and, 146 cystic fibrosis and, 259 neonatal, 596 Glucose transporter protein type 1 (GLUT1) deficiency, 510, 511 Glutaric aciduria I, 1047 Gluten-free diet (GFD), 163 Gluten sensitivity, 162–163 Glycerol kinase deficiency, 596 Glycine encephalopathy, 1047 Glycogen storage disease, 478, 479, 1047 Glycosylation disorders, 362, 363, 592, 1045 GM1 gangliosidosis, 1047 GM2 gangliosidosis, 1051 Goiter, 398–399, 404, 492, 493, 494 Goldenhar syndrome, 1050 Goltz syndrome, 32, 1047

Gonadal dysfunction, cancer therapy and, 147 Gonadal dysgenesis, 38–39 Gonadoblastoma, 384–385 Gonadotropin-releasing hormone (GnRH) agonists, 735 Gonococcal infections, 400–401 breast abscess, 126 cervicitis in, 168–169, 400, 401, 989 chlamydia coinfection with, 400, 401, 703 conjunctivitis in, 222, 223, 400, 401 dysuria in, 316, 317 epididymitis in, 336, 337, 400, 401 pelvic inflammatory disease in, 400, 401, 680, 681, 989 pharyngitis in, 400, 401, 702, 703, 862 sexual abuse and, 400, 401, 842–843 urethritis in, 400 vaginitis in, 988 Gonorrhea, 400–401. See also Gonococcal infections Goodpasture syndrome, 432 Gorlin syndrome, 154 Gout, in hereditary spherocytosis, 441 Gradenigo syndrome, 575 Graft-versus-host disease (GVHD), 72, 112–113, 146, 196, 402–403 in severe combined immunodeficiency, 840, 841 transfusion-associated, 948 Granulocyte colony-stimulating factor (GCSF), 61, 645 Granuloma, with pinworms, 708, 709 Granuloma gluteale infantum, 295 Granulomatous disease cavernous sinus syndrome in, 158 chronic, 190–191, 498 Granulomatous polyangiitis, 774 Graves disease, 72, 288, 398, 399, 404–405, 502, 623 Great arteries, transposition of, 956–957, 1041 Grooming, pathologic, 348, 962–963 Group A β-hemolytic Streptococcus, 884–885 in cellulitis, 164, 688 in diaper rash, 294, 295 in impetigo, 508 in otitis media, 668 in pelvic inflammatory disease, 680 in peritonsillar abscess, 622, 694

in pharyngitis, 702–703, 862–863 in rheumatic fever, 796 in scarlet fever, 818–819 in toxic shock syndrome, 884, 885, 938–939 in vaginitis, 989 Group A β-hemolytic Streptococcus vaccine, 884 Group B Streptococcus (GBS), in neonatal sepsis, 832, 833 Growth hormone (GH) cancer therapy and, 146 chronic kidney disease and, 195 for Turner syndrome, 970 22q11.2 deletion syndrome and, 266 Growth hormone deficiency, 406–407, 478, 479, 486–487, 844, 845 Growth parameters, for NICU graduates, 364, 365 Growth retardation/failure, 844 in chronic kidney disease, 195 in Crohn disease, 239 in cystic fibrosis, 258 in failure to thrive, 352–353 in fetal alcohol syndrome, 356–357 in giardiasis, 389 in hypoglycemia, 478 in hypothyroidism, 492, 493, 495 in inborn errors of metabolism, 595 intrauterine (See Intrauterine growth restriction) in severe combined immunodeficiency, 841 Guillain-Barré syndrome (GBS), 408–409 ataxia in, 78, 79, 408 Campylobacter infection and, 144, 145, 408 cat-scratch disease and, 157 Cyclospora infection and, 257 food poisoning and, 370 hypotonia in, 363 meningococcal vaccine in, 588 myasthenia gravis vs., 616 serum sickness and, 836, 837 vaccines and, 985 West Nile virus and, 1013 Zika virus and, 1024, 1025 Gum disease, 46, 390–391 Guttate psoriasis, 752

GVHD. See Graft-versus-host disease Gynecomastia, 410–411 H Haemophilus ducreyi, 170 Haemophilus influenzae, 338–339 in asplenia, 73 fever and petechiae with, 358 in meningitis, 586, 587 in otitis media, 668 in pelvic inflammatory disease, 680 in periorbital cellulitis, 688 in vaginitis, 989 Haemophilus influenzae type b vaccine, 73, 338, 358, 586, 662, 688, 830 Hair bezoars (trichobezoars), 102–103 Hair loss, 32–33 Hair tourniquet syndrome, 242 Hallermann-Streiff syndrome, 1047 Hamartomas, 728, 729, 966, 967 Hand, foot, and mouth disease, 412–413, 880, 881 Hand-Schüller-Christian syndrome, 448 Hartnup syndrome, 706, 707, 1047 Hashimoto-Pritzker syndrome, 448 Hashimoto thyroiditis, 288, 398, 399, 492, 623 Headache, 416–417 acute recurrent, 416 in brain vascular lesions, 992 chronic nonprogressive or daily, 416 chronic progressive, 416 cluster, 158, 416 in intracranial hemorrhage, 522 intracranial hypertension and, 496–497 mixed, 417 rebound, 417 tension, 416 Head and neck infections, anaerobic, 46, 47 Head banging, 414–415 Head lice, 550–551 Head trauma child abuse and, 178–179 developmental delay with, 282 hydrocephalus in, 460

subdural hematoma in, 890–891 syncope in, 904 traumatic brain injury in, 120–121 Hearing loss in Bell palsy, 100 in cancer therapy, 147 in cytomegalovirus infection, 260 developmental delay with, 282, 283 in diaphragmatic hernia, 297 in Down syndrome, 306, 307 in fragile X syndrome, 372, 373 in immune deficiency, 499 in Kawasaki disease, 536 in mastoiditis, 575 in mumps, 611 in NICU graduates, 364 in osteogenesis imperfecta, 661 in otitis media, 318, 319, 669 in persistent pulmonary hypertension of newborn, 696 in primary otalgia, 319 in renal tubular acidosis, 777 in severe combined immunodeficiency, 841 speech delay with, 864–865 speech problems with, 866, 867 in toxoplasmosis, 941 in Turner syndrome, 970 Heart failure, 220. See also Congestive heart failure Heart–lung transplantation, for cardiomyopathy, 153 Heart rate, 1038 Heart transplantation for cardiomyopathy, 153 for congestive heart failure, 221 for hypoplastic left heart syndrome, 488, 489 Heat cramps/spasms, 418, 419 Heat edema, 418, 419 Heat exhaustion, 418–419 Heat intolerance, in cystic fibrosis, 258 Heat stroke, 20, 418–419 Heat syncope, 418, 419 Heat tetany, 418, 419 Heavy metal poisoning, 282. See also Lead poisoning

Heiner syndrome, 432 Heinz body hemolytic anemia, 600 Helicobacter pylori, 6, 7, 380–381, 975 Heliox (helium/O2), 76, 241 HELLP syndrome, 20, 592 Hemangioblastoma, 122–123 Hemangioma, 420–421, 424, 432, 622, 992–993 Hemangiopericytoma, 420 Hematemesis, 528, 730, 731, 974, 1005 Hematochezia, 298, 528, 554, 555, 730, 731, 974 Hematoma epidural, 522, 890 neck, 623 subdural, 242, 522, 890–891 tendonitis/tendinosis and, 918 Hematopoietic stem cell transplantation (HSCT). See Stem cell transplantation Hematuria, 316, 317, 422–423 in glomerulonephritis, 394, 395, 422–423, 636 in hemophilia, 431 in Henoch-Schönlein purpura, 422, 434 in immunoglobulin A nephropathy, 504, 505 in nephrotic syndrome, 637 in polycystic kidney disease, 722 proteinuria with, 746 in renal venous thrombosis, 778 in serum sickness, 836 in urolithiasis, 980 Hemifacial microsomia, 1050 Hemifacial spasm, 934 Hemi-Fontan procedure, 488, 489 Hemimegalencephaly, 510 Hemiplegic migraine, 416 Hemochromatosis, 926, 927, 1047 hepatomegaly in, 436, 437 hereditary, 196 metabolic acidosis in, 592 neonatal, 20 in transfusion, 949 Hemoglobin H disease, 926, 927 Hemoglobinopathies. See also Sickle cell disease; Thalassemias hemolysis in, 424–425

microcytic anemia in, 602 Hemolysis, 424–425. See also specific hemolytic disorders in cholelithiasis, 184, 185 factitious hematuria in, 422, 423 in G6PD deficiency, 396–397, 424, 425 in thalassemia, 424, 425, 926 Hemolytic anemia, 424–425 autoimmune, 90–91, 424–425 in G6PD deficiency, 396–397 Heinz body, 600 in hemolytic uremic syndrome, 428–429 in hereditary spherocytosis, 440–441 in Wiskott-Aldrich syndrome, 1021 in Yersinia enterocolitica infection, 1023 Hemolytic disease of fetus or newborn (HDFN), 304, 426–427 Hemolytic uremic syndrome (HUS), 18, 194, 424, 425, 428–429 in Campylobacter infections, 145 in Epstein-Barr virus infection, 340 in food poisoning, 370–371 in G6PD deficiency, 396, 397 lower GI bleeding in, 554, 555 Hemophagocytic lymphohistiocytosis (HLH), 448 Hemophagocytic syndrome, 340, 341, 537, 676 Hemophilia, 430–431 abnormal bleeding with, 8 bruising with, 138, 139 intracranial hemorrhage with, 431, 522, 523 Hemoptysis, 259, 432–433, 756 Hemorrhagic cystitis, 26–27, 146, 422, 423 Hemorrhagic stroke, 522–523, 886–887 Hemorrhoids, in portal hypertension, 730, 731 Hemosiderosis, pulmonary, 432, 433 Henoch-Schönlein purpura (HSP), 434–435 abnormal bleeding in, 8 bruising in, 138, 139 cat-scratch disease and, 157 epididymitis with, 336 fever with petechiae in, 358 hematuria in, 422, 434 hemoptysis in, 432 IgA nephropathy vs., 504

intussusception in, 434, 435, 524 lower GI bleeding in, 554 in parvovirus B19 infection, 676 Hepatic abscess, 42–43, 436 Hepatic decompensation, 68, 69 Hepatic encephalopathy in acetaminophen poisoning, 20–21 in acute liver failure, 10–11 ascites in, 68 in cirrhosis, 196, 197 in portal hypertension, 730–731 Hepatic failure. See Liver failure Hepatic fibrosis, 192, 196 congenital, 197, 218–219 Hepatic mass, 2–3 Hepatic toxicity, in cancer therapy, 147 Hepatic venous outflow obstruction, 20 Hepatitis arboviral encephalitis and, 1013 autoimmune, 2, 20, 192, 196, 436, 532, 533 chronic, 192–193 cirrhosis with, 192, 196–197, 1001 cytomegalovirus and, 260, 1000 enteric fever and, 813 Epstein-Barr virus and, 340, 1000 fever of unknown origin in, 361 fulminant, 304, 1001 hepatomegaly in, 192, 436–437, 1000 immunoglobulin A deficiency with, 502 jaundice in, 192, 532, 533, 1000 liver failure in, 20–21 neonatal, cholestasis in, 632 parvovirus B19 and, 676, 1000 portal hypertension in, 730, 1001 posttransfusion, 949 tuberculosis treatment and, 965 viral, 20–21, 192, 1000–1001 Wilson disease and, 532 Hepatitis A, 1000–1001 Hepatitis A vaccine, 1001 Hepatitis B, 192, 1000–1001

blood transfusion and, 949 cervicitis with, 168 cirrhosis with, 196 polyarteritis nodosa with, 720 sexual abuse and, 843 Hepatitis B immune globulin, 1001 Hepatitis B vaccine, 572, 573, 843, 1001 Hepatitis C, 192, 1000–1001 blood transfusion and, 949 cancer therapy and, 147 cirrhosis with, 196, 197 human bites and, 573 Hepatitis D, 192, 1001 Hepatitis E, 1000 Hepatoblastoma, 2, 3, 20 Hepatocellular carcinoma, 20, 1001 Hepatocyte transplant, 1019 Hepatomegaly, 2–3, 436–437 atelectasis with, 80 cirrhosis and, 196, 436 congenital hepatic fibrosis and, 218 congestive heart failure vs., 221 cor pulmonale and, 232 cystic fibrosis and, 258, 436 cytomegalovirus and, 260, 436, 437 dengue infection and, 268 Epstein-Barr virus and, 340, 436, 437 food poisoning and, 370 hemolysis and, 424 hemolytic disease of fetus or newborn and, 426 hepatitis and, 192, 436–437, 1000 Hodgkin lymphoma and, 452 hyperammonemia and, 594 hyponatremia and, 482 immune thrombocytopenic purpura and, 500 infantile spasms and, 510 metabolic acidosis and, 592 myocarditis and, 618 neck masses and, 622 neonatal cholestasis and, 632 neonatal hypoglycemia and, 596

obesity and, 653 portal hypertension and, 437, 730 psittacosis and, 750 pulmonary hypertension and, 758 rickettsial disease and, 802 Salmonella infection and, 812 sarcoidosis and, 814 thalassemia and, 926 transposition of great arteries and, 956 tuberculosis and, 436, 964 tularemia and, 969 Wilson disease and, 436, 437, 1018 Hepatoportoenterostomy. See Kasai procedure Hepatopulmonary syndrome, 192, 730, 731 Hepatorenal syndrome, 730, 731 Hereditary angioedema (HAE), 212, 327, 338, 438–439 Hereditary ectodermal dysplasia, 154 Hereditary elliptocytosis, 425, 440 Hereditary fructose intolerance, 1047 Hereditary glomerulonephritis, 394 Hereditary hemochromatosis, 196, 197 Hereditary hemorrhagic telangiectasia, 1050 Hereditary multiple exostoses, 664 Hereditary spherocytosis, 2, 424, 425, 440–441 Hermansky-Pudlak syndrome, 706, 707, 1047 Hernia diaphragmatic, 80, 237, 296–297, 382, 696, 928, 1002 incarcerated, 242, 515, 518 inguinal, 2, 39, 62, 490, 514–515, 518 umbilical, 2 ventral, 2 Herniated disc, 96, 97, 820 Herpangina, 412, 880, 881 Herpes gladiatorum, 442 Herpes simplex virus (HSV), 442–443 Bell palsy with, 100 cervicitis with, 168–169 cholestasis with, 632, 633 congenital/postnatal, 364 conjunctivitis with, 222, 223, 442, 443 contact dermatitis vs., 226

developmental delay with, 282 diaper dermatitis vs., 295 dysuria with, 316 earache with, 318 encephalitis with, 326, 327, 442, 443, 523, 881 erythema multiforme with, 342, 343, 442, 878 genital, 442, 443, 843 gingivitis with, 390 hepatitis with, 1000 HSV-1, 442, 880 HSV-2, 442 meningitis with, 586, 587 neonatal, 442, 443 oropharyngeal, 442, 443 perinatal, 442 pharyngitis with, 442, 443, 702 sepsis with, 831, 832, 833 stomatitis with, 880 vaginitis with, 989 Wiskott-Aldrich syndrome with, 1020 Herpes zoster, 174–175 and Bell palsy, 100, 101 and earache, 318 Herpetic gingivostomatitis, 390, 412, 442, 880, 881 Herpetic whitlow, 442, 881 Heterotaxy syndrome, 72 Heterotopia, 510 Hexoaminidase deficiency, 78 Hiccups, 444–445 High-altitude cerebral edema (HACE), 36–37 High-altitude pulmonary edema (HAPE), 36–37 Highly active antiretroviral therapy (HAART), 455 Hip. See Femoral head Hip dysplasia, 284–285, 520, 521, 638 Hirschsprung disease, 446–447 appendicitis in, 62 constipation in, 224, 225, 446, 447 encopresis in, 328, 329 intestinal obstruction in, 518 lower GI bleeding in, 554 neuroblastoma in, 640

rectal prolapse in, 770 Hirsutism in obesity, 652, 653 in polycystic ovarian syndrome, 724, 725 in premature adrenarche, 736 Histamine 2 antagonists for gastritis, 380 for gastroesophageal reflux disease, 383 for peptic ulcers, 975 for short-bowel syndrome, 846 for urticaria, 983 Histiocytosis, 448–449, 623, 822 Histiocytosis X, 448 Histoplasmosis, 360, 361, 432, 450–451 HIV. See Human immunodeficiency virus (HIV) infection Hives. See Urticaria Hodgkin lymphoma, 452–453, 622 Holocarboxylase synthetase deficiency, 593 Holoprosencephaly, 406, 486, 510 Holter monitor, 153, 173, 552, 553, 631, 904, 996, 997 Holt-Oram syndrome, 678, 1047 Home cardiorespiratory monitoring, 631, 687 Homocystinuria, 392, 886, 1047 Honey botulism and, 114 for cough, 237 Hookworms, 66, 252–253, 571, 770 Hordeolum, 110 Hormone therapy. See also Oral contraceptives; specific hormones for abnormal uterine bleeding, 311 for acne, 13–15 for amenorrhea, 44, 45 for contraception, 228–230 for cryptorchidism, 247 for dysmenorrhea, 313 for infantile spasms, 511 for precocious puberty, 735 for pubertal delay, 755 for transgender youth, 951 for Turner syndrome, 970–971 Horner syndrome, 116–117, 154, 582, 583

Horseshoe abscess, 690 Horseshoe kidney, 506, 970 HSCT. See Stem cell transplantation Human bites, 572–573 Human granulocytic anaplasmosis (HGA), 324–325 Human herpesvirus 6, 100, 806, 826, 952 Human herpesvirus 7, 806, 826 Human immunodeficiency virus (HIV) infection, 454–455 Bell palsy in, 100 blood transfusion and, 949 cervicitis in, 168 chancroid in, 170 cryptococcal infections in, 244, 245 Cyclospora infection in, 256, 257 developmental delay in, 282 diarrhea in, 298 fever of unknown origin in, 360, 361 gingivitis in, 390 Guillain-Barré syndrome in, 408 hemolysis in, 424 hepatomegaly in, 436 histoplasmosis in, 451 immunization in, 984 immunoglobulin A nephropathy in, 504 meningococcal disease in, 588 in NICU patients, 364 osteomyelitis in, 662 parotitis in, 610 perirectal abscess in, 690, 691 Pneumocystis jiroveci in, 454–455, 714–715 postexposure prophylaxis for, 454, 573, 843 prenatal, intellectual disability with, 516 as secondary immune deficiency, 498, 499 sexual abuse and, 843 skin changes in, 82 splenic function in, 72 toxoplasmosis in, 455, 941 tuberculosis in, 964 Human monocytic ehrlichiosis (HME), 324–325 Human papillomavirus (HPV), 456–457, 843, 1008, 1009 Human papillomavirus (HPV) vaccine, 456, 457, 843, 1008

Human rabies immune globulin (HRIG), 767 Hungry bone syndrome, 465, 474, 484 Hunter syndrome, 460, 1049 Huntington disease, 1047 Hurler syndrome, 1049 HUS. See Hemolytic uremic syndrome Hutchinson-Gilford progeria syndrome, 1047 Hyaline membrane disease, 80 Hydatid cysts, 914, 915 Hydration, 264–265 Hydroa aestivale, 706 Hydroa vacciniforme, 706, 707 Hydrocele, 458–459, 514, 991 Hydrocephalus, 460–461 brain vascular lesions and, 993 developmental delay with, 282 in histoplasmosis, 451 infantile spasms with, 510 intellectual disability with, 516 in intracranial hemorrhage, 522, 523 L1CAM/X-linked, 1048 in neural tube defects, 460, 639 in neurofibromatosis, 460, 642 in NICU graduates, 364 in toxoplasmosis, 460, 940, 941 Hydrocolpos, 2, 506 Hydrometrocolpos, 2 Hydronephrosis, 462–463 abdominal mass with, 2, 3 cancer therapy and, 147 posterior urethral valves and, 732, 733 ureteropelvic junction obstruction and, 462, 463, 976–977 vesicoureteral reflux with, 462, 463, 998 Hydrops fetalis, 384, 426, 427, 676, 677, 926 Hydroureteronephrosis, 462, 463 Hydroxocobalamin, 585, 593 Hyperaldosteronism, 472, 480, 481 Hyperammonemia, 592, 593, 594–595, 790, 791 Hyperbaric oxygen treatment, for carbon monoxide poisoning, 151 Hyperbilirubinemia, 532–535 in hemolytic disease of fetus or newborn, 426–427

in hereditary spherocytosis, 440–441 in hypopituitarism, 486 in hypothyroidism, 494 in neonatal cholestasis, 632–633 in neonatal sepsis, 832 in pyloric stenosis, 764 in thalassemia, 926 Hypercalcemia, 157, 464–465 in hypocalcemia treatment, 475 in primary adrenal insufficiency, 743 in sarcoidosis, 815 Hypercalcemia of malignancy, 464 Hypercalciuria, 316, 317, 422, 423, 475, 815, 980 Hyperchloremic acidosis, 293, 776–777 Hypercholesterolemia, 470–471, 598–599. See also Hyperlipidemia Hyperekplexia, 1047 Hypereosinophilic syndrome (HES), 548 Hyperglycemia, 288, 290–291, 292 Hyperglycinemia, nonketotic, 1050 Hyperimmunoglobulin D (IgD) syndrome, 360 Hyperimmunoglobulinemia E syndrome (HIES), 466–467, 498–499 Hyperimmunoglobulin M (IgM) syndromes, 477, 498–499 Hyperinsulinism, 478–479, 596, 597, 724 Hyperkalemia in acute kidney injury, 19 in primary adrenal insufficiency, 743 in renal tubular acidosis, 776 in rhabdomyolysis, 792, 793 in tetanus, 923 Hyperleukocytosis, 23, 468–469 Hyperlipidemia, 470–471 in cancer therapy, 146 in chronic kidney disease, 195 in metabolic syndrome, 598–599 in obesity, 652 in polycystic ovarian syndrome, 724 Hypernatremia in diabetes insipidus, 287, 487 in malnutrition, 571 in rotavirus infection, 809 Hyperopia, 372, 772–773, 882, 970, 1056

Hyperoxaluria, 316, 981 Hyperoxia test, 1038 Hyperparathyroidism, 464–465, 474, 485 Hyperparathyroidism-jaw tumor syndrome, 464 Hyperphosphatemia, 474, 792 Hyperpigmentation, acne and, 12–15 Hyperprolactinemia, 44, 45, 146, 310, 410, 486 Hypersensitivity reaction, with food, 368–369 Hypersomnolence, in floppy infant syndrome, 362 Hypersplenism, 259, 424, 722 Hypertension, 472–473 in chronic kidney disease, 194, 195 in coarctation of aorta, 202 in glomerulonephritis, 394–395 in hemolytic uremic syndrome, 428, 429 in hyperimmunoglobulinemia E syndrome, 467 in hypokalemia, 480 in immunoglobulin A nephropathy, 504 intracranial hemorrhage in, 522 in metabolic syndrome, 598–599 in nephrotic syndrome, 636 in neurofibromatosis, 642 in obesity, 652, 653 in obstructive sleep apnea, 853 in polyarteritis nodosa, 721 in polycystic kidney disease, 722, 723 in polycystic ovarian syndrome, 724 in renal artery stenosis, 774–775, 779 in renal venous thrombosis, 778 in status epilepticus, 876 urolithiasis and, 980 Hypertensive emergencies, 473 Hypertensive urgencies, 473 Hyperthermia in acute liver failure, 20 in disseminated intravascular coagulation, 304 malignant, 418, 419, 1048 maternal, and neural tube defects, 638 rhabdomyolysis in, 792 in status epilepticus, 876 in sympathomimetic poisoning, 903

in varicocele, 990 Hyperthyroidism, 398, 399, 404–405, 410 alopecia with, 32 diabetes mellitus with, 288 in Down syndrome, 306 neck masses with, 622, 623 in 22q11.2 deletion syndrome, 266 weight loss in, 1010 Hypertriglyceridemia, 470–471. See also Hyperlipidemia Hypertrophic cardiomyopathy (HCM), 152–153, 172, 220, 996 Hypertropia, 882 Hyperuricosuria, 316 Hypervolemic hyponatremia, 482 Hypnagogic hallucinations, 620 Hypoalbuminemia, 322, 323, 465, 474, 475 Hypocalcemia, 474–475 postsurgical, 465 in rhabdomyolysis, 792, 793 in rickets, 800–801 in short-bowel syndrome, 847 in transposition of great arteries, 956 in 22q11.2 deletion syndrome, 266–267, 474 Hypochloremia, in pyloric stenosis, 754, 765 Hypocortisolism, 486–487 Hypogammaglobulinemia, 476–477, 498 Hypogastric pain, 6 Hypoglycemia, 478–479 in diabetes mellitus type 1, 289 in diabetes mellitus type 2, 291 in growth hormone deficiency, 406, 407, 478, 479 idiopathic ketotic, 478 in malnutrition, 570, 571 neonatal, 592, 596–597 postprandial, 478 in primary adrenal insufficiency, 743 in sepsis, 831 in transposition of great arteries, 956 Hypogonadism, 486, 1047 adrenal insufficiency with, 742, 743 cancer therapy and, 147 cryptorchidism with, 246

gynecomastia in, 410, 411 pubertal delay with, 754, 755 short stature with, 844 Turner syndrome and, 970 Hypogonadotropic hypogonadism, 246, 742, 743, 754, 1047 Hypokalemia, 480–481 in diabetic ketoacidosis, 293 in long QT syndrome, 552, 553 in malnutrition, 571 in pyloric stenosis, 754, 765 in refeeding syndrome, 571 in renal tubular acidosis, 776, 777 in salicylate poisoning, 811 in vitamin B12 repletion, 585 Hypokalemic periodic paralysis, 480 Hypomagnesemia, 474, 480, 481, 571, 847 Hypomelanosis of Ito, 510 Hypomelanotic macules, 966 Hyponatremia, 482–483 in adrenal insufficiency, 743 in diabetes insipidus, 287 in polycystic kidney disease, 723 in primary adrenal insufficiency, 743 in Rocky Mountain spotted fever, 805 seizures in, 482, 483, 825 in SIADH, 906–907 in sympathomimetic poisoning, 902 Hyponatremic encephalopathy, 482, 483 Hypoparathyroidism, 32, 474 Hypophosphatasia, infantile, 464 Hypophosphatemia, 293, 475, 481, 484–485, 570–571, 800–801 Hypophosphatemic disorders, 484–485 Hypophysitis, 486 Hypopituitarism, 478, 486–487. See also Diabetes insipidus; Growth hormone deficiency; Hypothyroidism cancer therapy and, 146 cholestasis in, 632, 633 short stature in, 487, 844 Hypoplastic left heart syndrome (HLHS), 220, 488–489, 930 Hypoplastic thorax syndrome, 928 Hypopnea, 852

Hypospadias, 38, 246, 306, 490–491, 514 Hyposplenia, 72–73 Hypotelorism, 486 Hypotension with hemolysis, 424 with lower GI bleeding, 554 with peritonitis, 692, 693 with status epilepticus, 876 with tracheitis, 943 with upper GI bleeding, 974 with volvulus, 1002 Hypothermia, 242, 304, 308–309, 374, 567 in hypothyroidism, 494 in peritonitis, 692 rhabdomyolysis in, 792 Hypothermia therapy, 634, 635 Hypothyroidism, 486–487 acquired, 492–493 alopecia in, 32, 492 ascites in, 68 breast development in, 738 central, 494 cholestasis in, 632, 633 congenital, 282, 494–495 diabetes mellitus with, 288 diabetic ketoacidosis with, 292 in Down syndrome, 306 goiter in, 398, 399, 492, 493, 494 growth hormone deficiency with, 406 hyperlipidemia in, 470, 471 iatrogenic, 492 intellectual disability with, 495, 516 intracranial hypertension in, 496 neck masses with, 622 obesity in, 652 short stature in, 844, 845 subclinical, 492, 493 transient, 494, 495 in 22q11.2 deletion syndrome, 266 Hypotonia in floppy infant syndrome, 362–363

in fragile X syndrome, 372 in hypothyroidism, 494 in muscular dystrophy, 614 in neonatal encephalopathy, 635 in spinal muscular atrophy, 362, 363, 868 Hypoventilation anti-seizure medication and, 825 in atelectasis, 80 central, congenital syndrome of, 132, 446, 640, 852 in floppy infant syndrome, 362, 363 obstructive, 852 polycythemia in, 726 pulmonary hypertension in, 758 in respiratory distress syndrome, 780 in spinal muscular atrophy, 868, 869 Hypovolemia in nephrotic syndrome, 637 in peritonitis, 693 Hypovolemic hyponatremia, 482 Hypovolemic shock, 433 Hypoxemia, 1033 Hypoxemia-induced pulmonary hypertension, 758 Hypoxia, 1033 apnea and, 630–631 crying in, 243 hyperammonemia and, 594 meconium aspiration and, 580–581 muscle, and rhabdomyolysis, 792 persistent pulmonary hypertension of newborn and, 696–697 pleural effusion and, 713 pneumothorax and, 719 pulmonary hypertension and, 759 in status epilepticus, 876, 877 in transient tachypnea of newborn, 955 Hypoxic-ischemic encephalopathy (HIE), 120, 364–365, 510, 634–635, 696, 697 Hypsarrhythmia, 510 I IBD. See Inflammatory bowel disease IBS. See Irritable bowel syndrome ICH. See Intracranial hemorrhage Ichthyoses, 154, 227, 1048

Idiopathic angioedema, 438 Idiopathic cavernous sinusitis, 158, 159 Idiopathic hypercalcemia of infancy, 464 Idiopathic intracranial hypertension (IIH), 496–497, 652, 653 Iliopsoas bleed, 431 Iliotibial band tendonitis, distal, 538 Illness scripts, 1031 Immotile cilia syndrome, 30 Immune-complex glomerulonephritis, 394 Immune deficiency, 498–499, 830 Immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome (IPEX), 498, 1048 Immune thrombocytopenic purpura (ITP), 138, 139, 358, 500–501 Immunocompromised patients. See Human immunodeficiency virus (HIV) infection; Immune deficiency Immunoglobulin A (IgA) deficiency, 162, 476, 498–499, 502–503 Immunoglobulin A (IgA) nephropathy, 194, 394, 422, 504–505, 1020 Immunoglobulin class-switch recombination (Ig-CSR), 476 Immunoglobulin D (IgD), hyper syndrome of, 360 Immunoglobulin E (IgE), hyper syndrome of, 466–467, 498–499 Immunoglobulin E (IgE)-mediated anaphylaxis, 48, 49 Immunoglobulin E (IgE)-mediated food allergy, 366, 367 Immunoglobulin M (IgM), hyper syndromes of, 477, 498–499 Immunosuppressive therapy for aplastic anemia, 61 for asthma, 76 for autoimmune hemolytic anemia, 91 for bone marrow/stem cell transplantation, 112 complications, in bone marrow/stem cell transplantation, 113 for contact dermatitis, 227 for Crohn disease, 239 for dermatomyositis/polymyositis, 281 and gingivitis, 390 for glomerulonephritis, 395 for graft-versus-host disease, 402, 403 for hemoptysis, 433 for Henoch-Schönlein purpura, 435 for immune thrombocytopenic purpura, 501 immunoglobulin A deficiency with, 502 for lupus erythematosus, 557 for morphea, 607 for myasthenia gravis, 617 for myocarditis, 619

for nephrotic syndrome, 636 for polyarteritis nodosa, 721 for psoriasis, 753 for refractory celiac disease, 163 renal tubular acidosis with, 776 for sarcoidosis, 815 for Stevens-Johnson syndrome/TEN, 879 for transverse myelitis, 959 and tuberculosis, 964 for ulcerative colitis, 973 for urticaria, 983 Impacted cerumen, 318 Imperforate anus, 224, 225, 306, 506–507, 518 Impetigo, 226, 294, 508–509 Implantable cardioverter defibrillator (ICD), 153, 553, 619, 997 Inborn errors of metabolism (IEM), 592–597 hyperammonemia with, 363, 592, 593, 594–595 hypercalcemia in, 464 hypoglycemia with, 596–597 hypotonia with, 363 infantile spasms with, 510 intellectual disability with, 516 jaundice with, 532, 533, 592, 594 megaloblastic anemia with, 585 metabolic acidosis with, 592–593 weight loss in, 1010 Incarcerated hernia, 242, 515, 518 Incontinence fecal (See Fecal incontinence) urinary (See Urinary incontinence) Incontinentia pigmenti, 32, 678, 1048 Incontinentia pigmenti achromians, 510 Indomethacin, 345, 481, 679, 873 Infant botulism, 114–115 Infantile acne, 12 Infantile cortical hyperostosis, 1048 Infantile hemangioma, 420–421 Infantile spasms, 510–511, 966, 967 Infectious blepharitis, 110 Infectious costochondritis, 234, 235 Infectious mononucleosis, 260, 340–341, 611, 622, 623

Infective endocarditis, 330–331. See also Endocarditis Inferior vena cava thrombosis, 930 Infertility cancer therapy and, 147 celiac disease and, 163 cervicitis and, 169 pelvic inflammatory disease and, 681 polycystic ovarian syndrome and, 724, 725 Infiltrative gingivitis, 390, 391 Inflammation, anemia of, 50–51, 602 Inflammatory blepharitis, 110 Inflammatory bowel disease (IBD), 238, 380, 972. See also Crohn disease; Ulcerative colitis Campylobacter infection and, 145 diarrhea in, 298, 299 fever of unknown origin in, 360, 361 hepatomegaly in, 436 immunoglobulin A deficiency with, 502 immunoglobulin A nephropathy in, 504 intestinal obstruction in, 518, 519 intussusception in, 524 iron deficiency in, 526 leukocytosis in, 548 lower GI bleeding in, 554, 555 malabsorption in, 566–567 pancreatitis in, 674 portal vein obstruction in, 160 pseudopolyps in, 728 splenic function in, 72 thrombosis in, 973 weight loss in, 1010 Wiskott-Aldrich syndrome and, 1021 Inflammatory bowel disease-associated arthropathy, 872–873 Inflammatory costochondritis, 234, 235 Influenza, 512–513 febrile seizures in, 826 hereditary spherocytosis with, 441 parotitis in, 610 sore throat in, 862 Influenza vaccine, 358, 512, 513, 848, 985 Inguinal hernia, 2, 39, 62, 490, 514–515, 518 Inhalational anthrax, 58–59

Injection anthrax, 58 Inner ear, barotrauma of, 98–99 Insect bites, 48, 748, 858–859. See also Mosquitoes In situ pulmonary artery thrombosis (ISPAT), 756 Insulin for diabetes mellitus type 1, 288–289 for diabetes mellitus type 2, 290–291 for diabetic ketoacidosis, 293 in hemolytic uremic syndrome, 429 inborn errors of metabolism, 596, 597 in metabolic syndrome, 598–599 in polycystic ovarian syndrome, 724–725 in premature adrenarche, 737 Insulinoma, 2, 478, 479 Intellectual disability, 516–517 with autism spectrum disorder, 88, 89, 516 with brain vascular lesions, 993 with developmental delay, 283, 516, 517 with Down syndrome, 306, 307, 516 with epilepsy/seizures, 824 with fetal alcohol syndrome, 357, 516 with fragile X syndrome, 372–373, 516 head banging with, 414 with hypothyroidism, 495, 516 with lead poisoning, 544, 545 learning disabilities vs., 546 with neurofibromatosis, 516, 643 in NICU graduates, 364 with phenylketonuria, 516 with renal tubular acidosis, 776, 777 speech delay with, 864 with toxoplasmosis, 516, 941 with tuberous sclerosis, 516, 966 with 22q11.2 deletion syndrome, 266, 267 Intersphincteric abscess, 690 Interstitial lung disease, 236–237 Interstitial pneumonitis, 260 Intertriginous candidiasis, 148 Intestinal atresia, 2, 518, 846 Intestinal infarction, 515 Intestinal mass, 2–3

Intestinal obstruction, 518–519 constipation with, 225 crying with, 242, 243 cystic fibrosis and, 258, 259 Meckel diverticulum and, 518, 578–579 Intestinal polyps, 554, 555, 728–729 Intestinal pseudoobstruction, 224, 846 Intestinal stenosis, 2 Intestinal strictures, in necrotizing enterocolitis, 625 Intoeing, 520–521 Intoxication, 893 alcohol, 28–29 cocaine, 172 opioid, 658–659 Intra-arterial chemotherapy (IAC), 785 Intracardiac thrombosis, 930 Intracranial hemorrhage (ICH), 522–523 in brain vascular lesions, 992, 993 in hemophilia, 431, 522, 523 in neonatal alloimmune thrombocytopenia, 628, 629 in premature infants, 522 in sickle cell disease, 522 Intracranial hypertension, idiopathic, 496–497, 652–653 Intracranial pressure (ICP), 208–209, 242–243, 496–497, 523, 652–653, 887, 891 Intraocular pressure, 392–393 Intraparenchymal hemorrhage, 522 Intrauterine devices (IUDs), 228, 230, 231, 313, 680 Intrauterine growth restriction (IUGR), 364 maternal obesity and, 652 metabolic acidosis and, 592 parvovirus B19 and, 677 and retinopathy of prematurity, 787 and short stature, 844, 845 Turner syndrome and, 970 Intraventricular hemorrhage (IVH), 364, 460, 522 Intussusception, 524–525 abdominal mass with, 2, 3, 524 crying with, 242, 243 diarrhea with, 299 Henoch-Schönlein purpura with, 434, 435, 524 intestinal obstruction with, 518, 519

lower GI bleeding with, 554, 555 mesenteric adenitis and, 591 rotavirus vaccine and, 809 Yersinia enterocolitica infection and, 1023 Invasive aspergillosis, 70, 71 Invasive candidiasis, 148, 149 Inverse psoriasis, 752 Iodine deficiency, 398 IPEX syndrome, 498, 1048 IRAK4 deficiency, 498 Iritis, 222 Iron deficiency anemia, 526–527, 602–603 with bezoars, 102, 103 with chronic disease, 50, 51 leukocytosis with, 549 in NICU graduates, 365 pallor in, 670–671 Iron excess. See Hemochromatosis Iron folate deficiency, 500 Iron overload, in transfusion, 949 Iron poisoning, 528–529 Iron supplementation, 526, 527, 603 for anemia of chronic disease, 51 for breath-holding spells, 131 for hemolytic disease of fetus or newborn, 427 for lead poisoning, 545 for pallor, 671 Irritable bowel of childhood, 376–377 Irritable bowel syndrome (IBS), 145, 254, 298, 530–531 Irritant contact dermatitis, 226, 227, 294–295 Ischemic stroke, 886–887, 930 Ischiorectal abscess, 690 Isoimmunization, 426–427 Isolated micronodular adrenocortical disease (iMAD), 250 Isopropyl alcohol, 936–937 Isospora belli, 257 Isovaleric acidemia, 592 IUGR. See Intrauterine growth restriction J Jacquet erosive diaper dermatitis, 295 Jactatio capitis nocturna, 414, 415

Jansen metaphyseal chondrodysplasia, 464, 1048 Japanese encephalitis, 326, 1012, 1013 Jarcho-Levin syndrome, 928 Jarisch-Herxheimer reaction, 559, 911, 933 Jaundice, 532–533 in acute liver failure, 20 in α1-antitrypsin deficiency, 35, 532, 533 in ascites, 68, 532 in biliary atresia, 104, 532, 533 breastfeeding-associated, 532, 534–535 in cholangitis, 218, 219 in food poisoning, 370 in G6PD deficiency, 396, 532, 533, 534, 535 in hemolysis, 424 in hemolytic disease of fetus or newborn, 426 in hepatitis, 192, 532, 533, 1000 in hereditary spherocytosis, 440, 441 in hypothyroidism, 494 in inborn errors of metabolism, 532, 533, 592, 594 in metabolic acidosis, 592 in neonatal cholestasis, 632–633 in neonatal sepsis, 832 in pancreatic pseudocyst, 672, 673 physiologic, 532, 534 in polycystic kidney disease, 722 in pyloric stenosis, 764 vomiting with, 1004 in Wilson disease, 532, 533, 1018 Jeune syndrome, 218, 928, 929 Job syndrome, 467 Johanson-Blizzard syndrome, 506, 1048 Jones criteria, modified, 796, 797 Joubert syndrome, 218 Juvenile dermatomyositis (JDM), 280–281 Juvenile idiopathic arthritis (JIA), 64–65, 96, 97 cataracts with, 154 fever of unknown origin in, 360, 361 leukocytosis in, 548 in 22q11.2 deletion syndrome, 266 weight loss in, 1010 Juvenile myasthenia, 616–617

Juvenile polymyositis (JPM), 280–281 Juvenile polyposis syndrome, 728, 729 Juvenile polyps, 728–729 Juvenile spring eruption (JSE), 706, 707 Juvenile xanthogranuloma, 448 K Kabuki syndrome, 1048 Kallmann syndrome, 486, 754, 755 Kaposiform hemangioendothelioma, 420 Kartagener syndrome, 30 Kasabach-Merritt syndrome, 304, 305, 424 Kasai procedure, 46, 105, 533, 633 Kawasaki disease (KD), 536–537 chest pain in, 172 congestive heart failure in, 220, 221 conjunctivitis in, 222 epididymitis in, 336 fever of unknown origin in, 360–361 neck mass in, 622, 623 renal artery stenosis in, 774 sore throat in, 862 thrombosis in, 536–537, 930 toxic shock syndrome with, 938 ventricular tachycardia in, 996 Kennedy disease, 868 Keratitis, 222, 442, 881 Keratoconjunctivitis, 26–27, 442, 443 Keratoconjunctivitis sicca, 110, 914 Keratolytics, 752, 823 Kernicterus, 426, 427, 533, 535 Kernig sign, 586 Ketoacidosis diabetic (See Diabetic ketoacidosis) neonatal, 592 Ketogenic diet, 511, 825 Kidney ectopic, 506 horseshoe, 506, 970 multicystic dysplastic, 2, 608–609, 774, 976 Kidney disease. See also specific diseases chronic, 50–51, 194–195

edema in, 322 hypercalcemia in, 464 hypertension in, 472–473 hypokalemia in, 480 in lupus erythematosus, 194, 195, 556–557 polycystic, 2, 194, 218, 422, 722–723 in systemic sclerosis, 913 tuberculosis with, 964 in tuberous sclerosis, 967 Kidney infection. See Pyelonephritis Kidney injury, acute, 18–19 in hemolytic uremic syndrome, 18, 428–429 in nephrotic syndrome, 637 in rhabdomyolysis, 18, 19, 792–793 in sepsis, 831 Kidney mass, 2–3 Kidney stones. See Nephrolithiasis Kidney toxicity, in cancer therapy, 147 Kidney transplantation, for hemolytic uremic syndrome, 429 Kingella kingae, 662, 663, 835 Klebsiella pneumoniae, 656, 716 Kleine-Levin syndrome, 621, 1048 Klinefelter syndrome, 38, 246, 384, 754, 1048 Klippel-Feil anomaly, 1048 Klippel-Trenaunay-Weber syndrome, 562 Klumpke palsy, 116–117 Knee pain, anterior, 538–539 Koebner phenomenon, 164 Koplik spots, 576 Krabbe leukodystrophy, 1048 Kugelberg-Welander disease, 868 Kuru, 744–745 Kussmaul sign, 684 Kwashiorkor, 32, 570–571 Kyphosis, 146, 303 L L1CAM/X-linked hydrocephalus, 1048 Labial adhesion, 316, 842 Labial fusion, 38 Labyrinthitis, 78, 575 Lacrimal duct obstruction, 540–541

LaCrosse encephalitis, 1012 Lactase deficiency, 464, 542–543 Lactic acidosis, congenital, 592, 597 Lactobacillus, 46 Lactobezoar, 102–103 Lactogenesis, 128 Lactose hydrogen breath test, 543 Lactose intolerance, 542–543 diarrhea in, 298, 299, 376, 377, 542–543 giardiasis and, 388, 389 Ladd procedure, 1003 Landau-Kleffner syndrome, 867 Langerhans cell histiocytosis (LCH), 2, 294, 295, 448–449, 822 Language or speech disorders, 546, 864–867 with ADHD, 86 in allergic rhinitis, 798 with autism spectrum disorder, 88, 864, 866, 867 with developmental delay, 282, 283, 866, 867 with diaphragmatic hernia, 297 in NICU graduates, 365 Larsen syndrome, 284, 1048 Larva migrans, cutaneous, 252–253 Laryngeal diphtheria, 300, 301 Laryngeal papillomatosis, 1008 Laryngocele, 622 Laryngomalacia, 132, 306, 354, 852, 946–947 Lassa fever, 320 Late effects of cancer therapy, 146–147 Late-onset sepsis (LOS), 832, 833 Latex allergy, 31, 48, 230, 637 Laxatives, 142, 225, 329 Lead encephalopathy, 544, 545 Lead poisoning, 282, 496, 516, 519, 544–545, 602, 603 Learning disabilities, 546–547 with ADHD, 86, 546 developmental delay vs., 283 with neural tube defects, 638 in NICU graduates, 365 stuttering with, 888 tics with, 934 Leber congenital amaurosis, 772

Leber hereditary optic neuropathy, 1048 Left coronary artery, anomalous, 54–55 Left lower quadrant pain, 6 Left upper quadrant pain, 6 Left ventricular hypertrophy (LVH), 195 Left ventricular noncompaction (LVNC), 152 Leg ulcers, in hereditary spherocytosis, 441 Leigh syndrome, 510 Leiomyosarcoma, 2 Lemierre syndrome, 46, 703 Lennox-Gastaut syndrome (LGS), 511, 621 LEOPARD syndrome, 1048 Leptospirosis, 360 Lesch-Nyhan syndrome, 414, 1048 Letterer-Siwe disease, 448 Leukapheresis, 469 Leukemia abdominal mass in, 2 acute lymphoblastic, 22–23, 147, 468 acute myeloid, 24–25, 147, 468, 548 acute promyelocytic, 24, 25 bruising in, 138, 139 chronic myeloid, 468 in Down syndrome, 22, 306 fever and petechiae in, 358 fever of unknown origin in, 361 leukocytosis in, 548, 549 liver failure in, 20 neck masses with, 623 subsequent, cancer therapy and, 147 Leukemoid reaction, 468 Leukocyte adhesion deficiency, 498, 499, 548, 549, 656 Leukocytosis, 548–549 Leukoreduction, 469 Leukorrhea, physiologic, 988, 1062 Leukostasis, 22, 25 Leukotriene modifiers, 76, 799, 853, 983, 1015 Levonorgestrel-releasing IUDs, 228, 313 Levothyroxine, 399, 487, 495 Libman-Sacks endocarditis, 557 Lice, 550–551, 988

Lichen planus, 32 Lichen sclerosus, 316, 705, 989 Liddle syndrome, 480 Life-threatening event, apparent, 132–133 Li-Fraumeni syndrome, 22, 122, 664, 794, 1048 Limb-girdle muscular dystrophy, 614–615 Linear morphea, 606 Lingual frenulum, in ankyloglossia, 52 Lip, cleft, 198–199, 486, 578 Lipomyelomeningocele, 638 Liposarcoma, 2 Lisch nodules, 642 Lissencephaly, 282, 510, 516 Listeriosis, 360, 370–371, 832, 1063 Lithium, 464, 776 Littre, hernia of, 514 Liver abscess, 42–43, 436 Liver disease. See also specific diseases edema in, 322 jaundice in, 532–533 polycystic, 722 portal hypertension in, 730–731 Liver failure acute, 10–11, 20–21 in iron poisoning, 528 in peritonitis, 692, 693 in polycystic kidney disease, 722 in Reye syndrome, 790–791 in Wilson disease, 1019 Liver mass, 2–3 Liver toxicity, in cancer therapy, 147 Liver transplantation for α1-antitrypsin deficiency, 35 for biliary atresia, 105, 196 for chronic hepatitis, 193 for cirrhosis, 196, 197 for congenital hepatic fibrosis, 219 for hemolytic uremic syndrome, 429 for hepatitis C, 1001 for liver failure, 11, 21 for neonatal cholestasis, 633

for portal hypertension, 731 for refractory ascites, 69 for Wilson disease, 1019 Lobar emphysema, 80 Localized scleroderma, 606–607 Loeys-Dietz syndrome, 604, 605, 1048 Loffler syndrome, 538 Long-acting reversible contraceptives (LARCs), 228 Long-acting β2 agonists (LABAs), 76 Long QT syndrome (LQTS), 552–553, 996, 997 Long thoracic nerve injury, 116 Louis-Bar syndrome, 1044 Lower gastrointestinal bleeding, 554–555 Lower urinary tract dysfunction, 106 Lowe syndrome, 154, 392, 776, 1048 Lowie syndrome, 636 Lucey-Driscoll syndrome, 532 Ludwig angina, 46, 275 Lung abscess, 717 Lung injury, transfusion-related acute, 948–949 Lupus erythematosus, 556–557 ascites in, 68 chest pain in, 172, 556 complement deficiency in, 212 congestive heart failure in, 221 fever of unknown origin in, 360, 361 Guillain-Barré syndrome in, 408 hematuria in, 422, 423 hemoptysis in, 432 immunoglobulin A deficiency with, 502 kidney disease in, 194, 195, 556–557 peritonitis in, 556, 692 photosensitivity in, 706, 707 splenic function in, 72 Lyme disease, 558–559 anaplasmosis with, 325 babesiosis with, 94, 95 Bell palsy with, 100, 101 encephalitis in, 326 erythema migrans in, 164, 558 fever of unknown origin in, 360, 361

Guillain-Barré syndrome in, 408 leukocytosis in, 548 meningitis in, 586, 587 Lymphadenitis, 561, 622, 648, 649 Lymphadenopathy, 560–561. See also specific conditions causing Lymphangioleiomyomatosis, 966 Lymphangioma, 2 Lymphangitis, 509, 562, 563 Lymphatic malformations, 420–421 Lymphatic obstruction, 322, 323 Lymphedema, 562–563 Lymphedema-distichiasis syndrome, 562, 1048 Lymphedema praecox, 562 Lymphedema tarda, 562 Lymph node abscess, 561 Lymphoblastic lymphomas, 646–647 Lymphocytic choriomeningitis virus, 360 Lymphocytic interstitial pneumonitis, 455 Lymphohistiocytosis, 20 Lymphoma, 452–453 abdominal mass, 2, 3 anaplastic large cell, 646 B-cell, 646–647, 1020 Burkitt, 340, 646 cryptogenic enteropathy-associated T-cell, 163 Epstein-Barr virus and, 340 fever of unknown origin in, 360 hemolysis with, 424 hemoptysis in, 432 Hodgkin, 452–453, 622 in hyperimmunoglobulinemia E syndrome, 467 liver failure with, 20 lymphoblastic, 646–647 neck masses with, 622 non-Hodgkin, 340, 622, 646–647 with tuberculosis, 964 Lymphoproliferative disorders, 424, 564–565 Lysosomal acid lipase deficiency, 192, 1048 Lyssaviruses, 766 M Macrocephaly, 460–461, 864, 890, 1051

Macrocytic anemia, 584 Macrocytosis, 584 Macrophage activation syndrome, 448, 498 Mad cow disease, 744, 745 Magic mouthwash, 413, 879, 881 Magnesium imbalance. See Hypomagnesemia Major depressive disorder (MDD), 278–279 Malabsorption, 566–567 in celiac disease, 162, 566–567, 844 in cystic fibrosis, 258, 566–567 in giardiasis, 388, 389, 566–567 hypocalcemia in, 474 in hypophosphatemic disorders, 484 in malnutrition, 570, 571 in necrotizing enterocolitis, 625 in portal hypertension, 731 rickets/osteomalacia in, 800 in short-bowel syndrome, 846–847 in short stature, 844 weight loss in, 1010 Malaria, 568–569 disseminated intravascular coagulation in, 304 fever of unknown origin in, 360 hemolysis in, 424 hepatomegaly in, 436 Malar (butterfly) rash, 556, 706 Malassezia, 83, 378–379, 822 Malignant histiocytosis, 448 Malignant hyperthermia, 418, 419, 1048 Mallory-Weiss tear, 974 Malnutrition, 570–571 delayed puberty in, 754 hypokalemia in, 480, 481 hypophosphatemia in, 484 Pneumocystis jiroveci in, 714 rectal prolapse in, 770 sepsis in, 830 short-bowel syndrome in, 846–847 short stature in, 844, 845 tuberculosis in, 964 weight loss in, 1010, 1011

Malrotation, 2, 518–519, 554, 764, 846, 1002–1003 Mammalian bites, 572–573, 766–767 Mammary duct fistula, 127 Mandibular fracture, 276, 277 Mandibulofacial syndromes, 154 Maple syrup urine disease, 510, 592, 593 Marasmus, 32, 570–571 Marburg hemorrhagic fever, 320 March hemoglobinuria, 424 Marfan syndrome, 154, 172, 392, 514, 772, 774, 1048 Marijuana use, 892 Maroteaux-Lamy syndrome, 460 Masked hypertension, 472 Masked mastoiditis, 574 Massive macronodular adrenal hyperplasia (MMAD), 250 Mastitis, 126–127, 128, 129, 611 Mastodynia, 126 Mastoidectomy, 575 Mastoiditis, 318, 319, 574–575 Masturbation, 316 Maturity-onset diabetes of youth (MODY), 288, 290 Mauriac syndrome, 289 Maxilla fractures, 276 McCune-Albright syndrome, 217, 404, 484, 734, 735, 738, 1049 McKusick-Kaufman syndrome, 506 MDMA, 902 MDPV (bath salts), 902 Measles (rubeola), 576–577 conjunctivitis in, 222, 576 encephalitis in, 326, 577 fever of unknown origin in, 361 modified, 576 pneumonia in, 577 typical, 576 Measles, mumps rubella, and varicella (MMRV) vaccine, 610 and rubella (MMR) vaccine, 326, 386, 576, 577, 610, 611, 984–985 Meatal stenosis, 316, 422, 682, 683 Meckel diverticulum, 578–579 abdominal mass with, 2, 3 bleeding with, 526, 554, 555, 578–579

in Down syndrome, 306 in hernia of Littre, 514 intestinal obstruction with, 518, 578–579 intussusception with, 524 iron deficiency anemia with, 526 Rule of 2’s for, 578 Meckel-Gruber syndrome, 218, 1049 Meckel syndrome, 638 Meconium aspiration syndrome, 580–581, 696 Meconium ileus, 2, 258, 518, 519, 846 Meconium peritonitis, 518, 692 Meconium plug syndrome, 518 Meconium-stained amniotic fluid, 580 Mediastinal mass, 582–583, 646 Mediastinitis, 451, 789 Medical child abuse, 478, 612–613 Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, 1049 Medulloblastoma, 78, 122–123 Megacalycosis, 976 Megacolon, 2, 3, 239, 507, 973 Megalencephaly, 460 Megaloblastic anemia, 584–585, 847 Megaureter, 462, 976 Meige disease, 562, 1049 Melanoma, 623 MELAS syndrome, 886, 1049 Melatonin, 373, 417 Melena, 554, 555, 731, 974 Melkersson-Rosenthal syndrome, 100 Membranoproliferative glomerulonephritis (MPGN), 194, 394, 395 Membranous nephropathy, 194 Ménétrier disease, 380 Meningioma, 122–123 Meningismus with anthrax, 58 with ataxia, 78 with brain abscess, 119 with fever and petechiae, 358, 359 with pharyngoconjunctival fever, 26 with psittacosis, 750 with rabies, 766

with Rocky Mountain spotted fever, 804 with seizures, 824, 876 with sepsis, 830 with transverse myelitis, 958 Meningitis, 586–587 anthrax, 58 aseptic, 586, 587, 610, 611, 807, 933 aspergillosis, 586 bacterial, 326–327, 358, 359, 586–587 coccidioidomycosis and, 204, 205, 586 crying in, 242, 243, 586 cryptococcal, 244–245, 586 cytomegalovirus, 260 developmental delay in, 282 fever and petechiae in, 358, 359 fungal, 586–587 gonococcal, 401 herpes simplex, 586, 587 histoplasmosis, 450, 451 hydrocephalus in, 460 infantile spasms with, 510 mastoiditis and, 575 mumps, 586, 610, 611 plague, 711 roseola, 807 Salmonella, 813 sepsis and, 831, 832, 833 sinusitis and, 851 tick fever, 933 toxoplasmosis, 941 tuberculous, 586–587, 964, 965 tularemia, 969 viral, 586–587 Wiskott-Aldrich syndrome, 1020 Meningococcal disease asplenia and, 73 fever and petechiae in, 358–359 meningitis in, 586, 587 meningococcemia in, 138, 139, 588–589 septic arthritis in, 834, 835 Meningococcal vaccine, 73, 358, 586, 588, 589, 830, 848

Meningococcemia, 138, 139, 588–589 Meningoencephalitis, 260, 340 Meniscus tear, 538 Menkes disease, 510, 890, 1049 Menstrual pain, 312–313 Menstruation, absence of (amenorrhea), 44–45, 724 Mesenteric adenitis, 2, 68, 340, 590–591, 1022, 1023 Mesenteric fibromatosis, 2 Mesenteric lymphadenitis, 157 Mesenteric mass, 2–3 Mesoblastic nephroma, 2 MesoRex bypass, 731 Mesothelioma, 2 Metabolic acidosis in necrotizing enterocolitis, 624, 625 neonatal, 592–593 in renal tubular acidosis, 776–777 in rotavirus infection, 809 in short-bowel syndrome, 847 in transposition of great arteries, 956 Metabolic diseases in acidotic newborns, 592–593 in hyperammonemic newborns, 594–595 in hypoglycemic newborns, 596–597 Metabolic stroke, 592, 595 Metabolic syndrome, 598–599, 652, 724, 725 Metachromatic leukodystrophy, 1049 Metatarsus adductus, 200, 520–521 Methamphetamine, 902, 996 Methanol, 936–937 Methemoglobinemia, 600–601, 726 Methicillin-resistant Staphylococcus aureus (MRSA) in atopic dermatitis, 83 in breast abscess, 126 in cellulitis, 164–165, 688, 689 in cervical adenitis, 623 in impetigo, 508, 509 in lymphadenitis, 561 in neonatal sepsis, 833 in omphalitis, 656, 657 in osteomyelitis, 662, 663

in peritonsillar abscess, 695 in pneumonia, 717 in scalded skin syndrome, 875 in septic arthritis, 835 in toxic shock syndrome, 939 in tracheitis, 943 Methylmalonic aciduria, 510, 592 Methylxanthines. See also Caffeine for apnea of prematurity, 631 for bronchopulmonary dysplasia, 136 for wheezing, 1015 Microcephaly, 864, 941, 1024 Microcytic anemia, 602–603, 926–927 Micropenis, 38, 486, 632, 844 Microsporidia, 256 Midaortic syndrome, 774 Midchildhood acne, 12 Middle ear barotrauma of, 98–99 infection of (See Otitis media) Middle ear effusion (MEE), 668 Middle East respiratory syndrome (MERS), 838, 839 Migraine, 416–417 abdominal, 4–5, 416 ataxia with, 78, 79 confusional, 416 cyclic vomiting syndrome with, 254, 255 earache in, 319 hemiplegic, 416 ophthalmoplegic, 158 patent foramen ovale and, 85 Milia, 604–605 Milia en plaque, 604 Miliaria rubra, 418 Miliary tuberculosis, 965 Milk thistle, 129 Miller-Dieker syndrome, 510, 1049 Miller-Fisher syndrome, 145, 408 Milroy disease, 562 Mineralocorticoids, 480, 743, 777 Mineral oil, 225, 329

Mini-clinical evaluation exercise (mini-CEX), 1029 Minimal change nephrotic syndrome (MCNS), 636–637 Mirizzi syndrome, 185 Miserable malalignment syndrome, 538 Mismatch repair cancer syndrome, 1049 Mitochondrial disorders, 192, 592, 776 Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms (MELAS), 886, 1049 Mitral regurgitation, 797 Mitral stenosis, 797 Mitral valve prolapse, 372, 722 Mixed apnea, 132, 630 Mixed gonadal dysgenesis (MGD), 38 Mixed headache, 417 Mixed receptive and expressive language disorders, 864 Möbius syndrome, 883, 1049 Modern staged repair of bladder exstrophy (MSRE), 350 Moleskin, for warts, 1009 Mondor disease, 126 Monilethrix, 32, 1049 Monoarticular articular, 64 Mononucleosis, 260, 340–341, 611, 622, 623 Monosymptomatic nocturnal enuresis (MNE), 332 Mood disorders. See Anxiety disorders; Depression Morgagni hernia, 296 Morphea, 606–607 Morquio syndrome, 1049 Mosquitoes and Chikungunya virus, 176–177 and dengue virus, 268 and encephalitis, 1012–1013 and malaria, 568 and Zika virus, 1024–1025 Mothballs, and G6PD deficiency, 396, 397 Motor speech disorders, 866 Mounier-Kuhn syndrome, 1015 Mowat-Wilson syndrome, 446 Moyamoya disease, 774, 886 MRSA. See Methicillin-resistant Staphylococcus aureus Muckle-Wells syndrome, 982 Mucocutaneous candidiasis, 148, 149 Mucolytics, 259, 851

Mucopolysaccharidoses, 436, 437, 460, 514, 852, 1049 Mucormycosis, 159, 293 Mucosal dryness, nosebleeds with, 650 Mucositis in bone marrow/stem cell transplantation, 113 in erythema multiforme, 342, 343 Mycoplasma-induced, 342, 878, 879 Multicystic dysplastic kidney (MCDK), 2, 608–609, 774, 976 Multidrug-resistant tuberculosis, 965 Multinodular goiter, 398 Multiple carboxylase deficiency, 592 Multiple enchondromatosis, Maffucci type, 1049 Multiple endocrine neoplasia (MEN), 398, 446, 464, 478, 1049 Multiple epiphyseal dysplasia, 1049 Multiple eruptive milia (MEM), 604 Multiple exostoses, 1049 Multiple sclerosis (MS), 78, 958 Mumps, 610–611 Bell palsy with, 100 earache in, 319 encephalitis in, 326, 611 meningitis in, 586, 610, 611 Munchausen syndrome by proxy, 478, 612–613 Murine typhus, 802 Muscular dystrophies (MDs), 614–615 atelectasis in, 80 cor pulmonale in, 232 developmental delay in, 282 Fukuyama, 1047 Muscular dystrophy-dystroglycanopathy with brain and eye anomalies, 1049 Musculoskeletal toxicity, in cancer therapy, 147 Mutism, selective, 88, 860, 866 MUTYH-associated polyposis syndrome, 728 Myasthenia gravis, 79, 115, 362, 363, 616–617, 882 Myasthenic crisis, 617 Myasthenic syndromes, 362–363 Mycobacterial infection in cystic fibrosis, 258, 259 fever of unknown origin in, 360, 361 neck masses with, 622 nontuberculous (atypical), 622, 648–649

Mycobacterium abscessus, 648, 649 Mycobacterium avium intracellulare, 455, 648, 649 Mycobacterium chelonae, 648, 649 Mycobacterium fortuitum, 648, 649 Mycobacterium kansasii, 648, 649 Mycobacterium malmoense, 648 Mycobacterium marinum, 648, 649 Mycobacterium tuberculosis, 964. See also Tuberculosis Mycobacterium ulcerans, 649 Mycobacterium xenopi, 648 Mycoplasma encephalopathy, 326, 327 Mycoplasma-induced mucositis, 878, 879 Mycoplasma-induced rash and mucositis (MIRM), 342 Mycoplasma pneumoniae, 100, 342, 878 MyD88 deficiency, 498 Myelitis, transverse, 157, 958–959 Myelocystocele, 638 Myelodysplastic syndrome (MDS), 24, 25, 60–61, 147, 584 Myelofibrosis, 1050 Myeloid leukemia, 24–25, 147, 468, 548 Myelomeningocele (MMC), 284, 506, 507, 638–639, 770 Myeloschisis, 638–639 Myobacterium tuberculosis, 586 Myocardial infarction, 537, 557, 903, 930 Myocarditis, 618–619 with adenovirus infection, 26, 27 cardiomyopathy in, 152, 153 with diphtheria, 301 with encephalitis, 1013 with enteric fever, 813 with Epstein-Barr virus, 340 heart failure in, 220, 221, 618, 619 with Kawasaki disease, 536 with Lyme disease, 558 with measles, 577 with meningococcemia, 589 with mumps, 611 pericarditis vs., 684 with systemic sclerosis, 914 with toxoplasmosis, 941 ventricular tachycardia in, 996

Yersinia enterocolitica infection and, 1023 Myoclonus, 510, 934 Myoglobinuria, 513 Myonecrosis, 656, 657 Myopathic facies, 362 Myopericarditis, 684 Myopia, 364, 772–773, 787, 1056 Myositis, 280–281, 513, 792 Myotonic dystrophy, 154, 362, 363, 620, 1050 Myringitis, 318 Myringotomy, 98, 99, 575 Myxedema, 322, 323, 492 Myxedema coma, 493 N N-acetylcysteine for acetaminophen poisoning, 10–11, 21 for acute kidney injury, 19 for lavage in atelectasis, 81 for phytobezoars, 103 for trichotillomania, 962 for Wilson disease, 1019 NADH-dependent methemoglobinemia, 600 Nail infections, fungal, 378–379 Nail-patella syndrome, 636, 1050 Nalmefene, withdrawal induced by, 16–17 Naloxone, 16, 659 Naltrexone, 16, 193 Narcolepsy, 620–621 Nasal diphtheria, 300 Nasal polyps, 30, 258, 259, 798 Nasogastric decompression, 519, 1002 Nasolacrimal duct obstruction, 222, 772 Nasolacrimal duct stenosis, 306 Nasopharyngeal carcinoma, 340 Natural clay powder, 531 Near drowning, 308 Near-sightedness (myopia), 364, 772–773, 787, 1056 NEC. See Necrotizing enterocolitis Necator americanus, 66 Neck abscesses, 575 Neck masses, 622–623

Necrotizing enterocolitis (NEC), 624–625 disseminated intravascular coagulation in, 304, 624, 625 intestinal obstruction with, 518, 519 lower GI bleeding with, 554 in NICU graduates, 364 omphalitis with, 656, 657 patent ducts arteriosus and, 679 short-bowel syndrome in, 625, 846 Necrotizing fasciitis, 127, 164, 884 Neisseria gonorrhoeae, 400. See also Gonococcal infections Neisseria meningitidis, 586–589. See also Meningococcal disease Nelson syndrome, 251 Nematodes, 66–67, 252–253, 708–709 Neonatal abstinence syndrome (NAS), 16–17, 364, 626–627 Neonatal acne, 12, 604 Neonatal alloimmune thrombocytopenia (NAIT), 628–629 Neonatal anaerobic infections, 46 Neonatal apnea, 630–631 Neonatal candidiasis, 148, 149 Neonatal cholestasis, 632–633 Neonatal encephalopathy, 634–635 Neonatal gynecomastia, 410–411 Neonatal hemochromatosis, 20 Neonatal intensive care unit (NICU), follow-up of graduates, 364–365 Neonatal lupus erythematosus, 557 Neonatal myasthenia, 616–617 Neonatal sepsis, 832–833 Neonatal severe hyperparathyroidism (NSHPT), 464, 465 Nephrectomy, 1017 Nephritic syndrome, 394, 504 Nephritis hematuria in, 422–423 in lupus erythematosus, 556 in mumps, 611 of systemic disease, 422 Nephroblastoma (Wilms tumor), 2–3, 422, 1016–1017 Nephroblastomatosis, 1016 Nephrocalcinosis, 776, 777 Nephrolithiasis (kidney stones), 980–981 in Crohn disease, 238, 239 dysuria with, 316, 317

hematuria in, 422, 423 in histoplasmosis, 451 in polycystic kidney disease, 722, 723, 763 in pyelonephritis, 762 in renal tubular acidosis, 777 in rickets/osteomalacia, 800 in short-bowel syndrome, 847 Nephroma, 2 Nephronophthisis (NPHP), 194, 218, 722, 1050 Nephropathy contrast, 18–19 diabetic, 288, 289, 291 immunoglobulin A, 194, 394, 422, 504–505, 1020 membranous, 194 Nephrotic syndrome, 636–637 ascites in, 68, 69, 636 congenital, 194, 636 edema in, 322, 323 IgA nephropathy and, 504, 505 malaria and, 568 minimal change, 636–637 peritonitis in, 637, 692 proteinuria in, 636, 746 renal artery stenosis and, 774 renal venous thrombosis and, 778 thrombosis in, 930 Netherton syndrome, 1050 Neural tube defects (NTDs), 460, 638–639 Neuraminidase inhibitors, 513 Neuroblastoma, 623, 640–641 Neurocysticercosis, 118, 119, 914–915 Neuroendocrine tumors, 2, 250 Neurofibroma, 642–643 Neurofibromatosis-1, 642–643, 1050 brain tumors in, 122 cataracts in, 154 developmental delay in, 282 glaucoma in, 392 hydrocephalus in, 460, 642 infantile spasms in, 510 intellectual disability in, 516, 643

leukemia in, 22 renal artery stenosis in, 774 rhabdomyosarcoma in, 794 short stature in, 845 Neurofibromatosis-2, 642, 1050 Neurogenic bladder, 2, 194, 262, 637, 638 Neurogenic bowel, 638 Neuroleptic malignant syndrome, 419, 792 Neurologic toxicity, in cancer therapy, 147 Neuromyelitis optica spectrum disorder (NMOSD), 958–959 Neuropathy acute motor axonal, 408 cancer therapy and, 147 diabetic, 288, 289, 291 serum sickness and, 836, 837 Neuropraxia, 116 Neuroretinitis, 157 Neurosarcoidosis, 814, 815 Neurosyphilis, 910, 911 Neurotmesis, 116 Neutropenia, 498, 644–645 candidiasis in, 148 cyclic, 644–645, 1045 with mediastinal mass, 582 in meningococcemia, 589 in necrotizing enterocolitis, 624, 625 in omphalitis, 656 perirectal abscess with, 690, 691 in transient erythroblastopenia of childhood, 953 Nevus flammeus, 420, 421 Nevus simplex, 420, 421 Niacin, 471, 706, 707 Nicotine dependence, 893 Nicotine withdrawal, 16–17 NICU graduates, follow-up of, 364–365 Niemann-Pick disease, 2, 78, 620, 1050 Nighttime sleep fragmentation, 620 Nikolsky sign, 874 Nipple infection, candidal, 128, 129 Nipples, cracked, 128, 129 Nitazoxanide, 43, 67, 249, 257, 389

Nitric oxide, inhaled, 233, 581, 697, 759 Nocturia, 288 Nocturnal enuresis, 106, 262, 328, 332–333 Nonalcoholic fatty liver disease (NAFLD), 196, 436, 598, 652, 653, 724 Nonalcoholic steatohepatitis (NASH), 192, 196, 652 Nonexertional heat stroke, 418 Non-Hodgkin lymphoma, 340, 622, 646–647 Non–IgE-mediated food reaction, 366, 368–369 Noninvoluting congenital hemangioma (NICH), 420 Nonketotic hyperglycinemia, 1050 Non-monosymptomatic nocturnal enuresis (NMNE), 332 Nonsteroidal anti-inflammatory drugs (NSAIDs) abnormal bleeding with, 8 acute kidney injury with, 18 for avascular necrosis of femoral head, 93 for back pain, 97 for breast abscess, 127 bruising with, 138 for chest pain, 173 for Chikungunya virus infection, 177 for concussion, 215 for dental pain, 271, 274 for diskitis, 303 for dysmenorrhea, 313 for earache, 319 for epididymitis, 337 for Epstein-Barr virus infection, 341 for erythema nodosum, 345 for frostbite, 375 gastritis with, 380, 381 hematuria with, 422 for intestinal polyps, 729 for juvenile idiopathic arthritis, 64, 65 for lupus erythematosus, 557 for migraine, 417 for otitis media, 668 for patent ductus arteriosus, 679 for Perthes disease, 699 for premenstrual syndrome, 741 renal tubular acidosis with, 776 for sarcoidosis, 815

for serum sickness, 837 serum sickness with, 836 for sickle cell disease, 849 for sore throat, 863 for spondyloarthropathy, 873 for stomatitis, 881 for tendonitis/tendinosis, 919 for transient synovitis, 909 upper GI bleeding with, 974 Nontuberculous mycobacterial infections, 622, 648–649 Noonan syndrome, 246, 562, 844, 845, 1050 Noonan syndrome with multiple lentigines, 1048 Norrie disease, 621, 1050 Norwegian scabies, 816 Norwood procedure, 488 Nosebleeds, 431, 650–651 Nummular eczema, 164, 226 Nursemaid’s elbow, 768–769 Nutcracker syndrome, 422, 990 Nystagmus, 306 O Obesity, 652–653 apnea in, 652, 852, 853 asthma in, 652 atelectasis in, 80 candidiasis in, 148 cholelithiasis in, 184 daytime incontinence in, 262 in Down syndrome, 306, 852 growth hormone in, 406 hyperlipidemia in, 470, 471 hypertension in, 472 hypothyroidism in, 492 in metabolic syndrome, 598–599, 652 in polycystic ovarian syndrome, 652, 724 psoriasis in, 752 slipped capital femoral epiphysis in, 854, 855 transgender youth and, 950 in 22q11.2 deletion syndrome, 267 Obesity-hypoventilation syndrome, 852 Obesity (bariatric) surgery, 599, 653

Obsessions, 654 Obsessive-compulsive disorder (OCD), 56, 86, 88, 266, 348, 654–655 separation anxiety disorder with, 828 social anxiety with, 860 tics with, 934, 935 trichotillomania with, 962 Obstructive hypoventilation, 852 Obstructive sleep apnea syndrome (OSAS), 630–631, 852–853 in brief resolved unexplained event, 132 in cor pulmonale, 232 in Down syndrome, 306, 307 in metabolic syndrome, 598 in obesity, 652, 653 pulmonary hypertension in, 758, 759 Obstructive uropathy, 194, 262 Obturator sign, 62 Occult spinal dysraphism, 638–639 Ochoa syndrome, 262 Ocular bruit, 154 Ocular rosacea, 110 Ocular syphilis, 910 Ocular toxoplasmosis, 940 Ocular trachoma, 180 Oculo-auriculo-vertebral spectrum, 1050 Oculocerebrorenal syndrome, 392 Oculoglandular tularemia, 968 Oculomandibulofacial syndrome, 32 Odynophagia, 862 Ohtahara syndrome, 511 Oil of wintergreen, toxicity of, 810, 811 Oligoarticular arthritis, 64, 65 Oligohydramnios hip dysplasia with, 284 hydronephrosis with, 462, 463 persistent pulmonary hypertension with, 696 polycystic kidney disease with, 722 posterior urethral valves with, 732, 733 ureteropelvic junction obstruction with, 976 Oligospermia, cancer therapy and, 147 Omega-3 fatty acids in asthma, 77

in blepharitis, 111 in depression, 279 in necrotizing enterocolitis, 624 in seborrheic dermatitis, 823 in short-bowel syndrome, 847 Omenn syndrome, 841, 1050 Omphalitis, 160, 656–657, 692, 832 Omphalocele, 2, 478, 506, 514, 578, 846, 924, 1002 Omphalocele-exstrophy of the bladder-IA-spinal defects (OEIS) complex, 506 Omphalomesenteric cyst, 578 Omphalomesenteric duct, persistent, 656 Omphalomesenteric fistula, 578 Onychomycosis, 378–379 Oophoritis, 611 Ophthalmia neonatorum, 222, 223, 400, 401 Ophthalmologic toxicity, in cancer therapy, 147 Ophthalmoplegic migraine, 158 Opioid(s) “designer,” 659 for dyspnea, 315 for pain in sickle cell disease, 849 for sore throat, 863 Opioid abuse/dependence, 892, 893 Opioid intoxication, 658–659 Opioid withdrawal, 16–17, 626–627, 658, 659 Opitz-Kaveggia syndrome, 506 Opitz syndrome, 1050 Opportunistic infections, 498–499 Oppositional defiant disorder, 86, 278, 934 Opsoclonus-myoclonus syndrome, 78 Optic ataxia, 79 Optic atrophy syndrome, 510 Optic nerve atrophy, 787 Optic neuritis, 157, 851, 1013 Optic pathway tumors (OPTs), 642 Oral allergy syndrome, 366 Oral candidiasis (thrush), 128, 148, 149, 294, 499, 840 Oral contraceptives, 228–231 for abnormal uterine bleeding, 311 for acne, 14–15 amenorrhea with, 44, 45

for dysmenorrhea, 313 gingivitis with, 390 hyperlipidemia with, 470 hypertension with, 472 photosensitivity with, 706 for polycystic ovarian syndrome, 725 portal hypertension with, 730 for premenstrual syndrome, 741 renal venous thrombosis with, 778 Oral-facial-digital syndrome, 52, 218, 604, 605, 1050 Oral habits, nonfunctional or parafunctional, 140 Oral hygiene, 272–273 Oral motor disorder, 354 Oral rehydration therapy (ORT), 264–265, 269, 299 for cholera, 187 for food poisoning, 371 for functional diarrhea of infancy, 376 in Salmonella infections, 813 for vomiting, 1005 Oral toxicity, in cancer therapy, 147 Orbital abscess, 851 Orbital cellulitis, 164, 165, 541, 688, 851 Orchiectomy, 459, 921 Orchiopexy, 247, 384, 459 Orchitis, 340, 921 Organic acidemias, 363, 510, 592–597 Organophosphate ingestion, 616 Ornithine transcarbamylase (OTC) deficiency, 594, 595 Orofacial syndrome, 262 Oropharyngeal tularemia, 968 Orthodontics, in cleft lip and palate, 199 Orthostatic proteinuria, 746 Ortolani test, 284 Osgood-Schlatter disease, 538 Osler-Weber-Rendu syndrome, 1050 Osmotic diarrhea, 188, 298 Osteitis, 12 Osteogenesis imperfecta, 660–661 Osteomalacia, 800–801 Osteomyelitis, 662–663 back pain in, 96

in candidiasis, 148, 663 in cat-scratch disease, 157 coccidioidomycosis and, 204, 205 in diskitis, 303 fever of unknown origin in, 361 in food poisoning, 370 in gonococcal infection, 401 in impetigo, 509 in mastoiditis, 575 in neonatal sepsis, 832 in Salmonella infections, 662, 663, 813 in sinusitis, 851 Osteopenia in anorexia nervosa, 56 in celiac disease, 163 in Crohn disease, 239 in hyperimmunoglobulinemia E syndrome, 466 of prematurity, 365 in renal tubular acidosis, 776 in spinal muscular atrophy, 869 Osteopetrosis, 1050 Osteoporosis in anorexia nervosa, 56 back pain in, 96 in celiac disease, 163 in Crohn disease, 239 in cystic fibrosis, 258, 259 in hypopituitarism, 487 in renal tubular acidosis, 776 Osteoradionecrosis, 147 Osteosarcoma, 664–665 Otalgia, 318–319, 668–669 Otitis externa, 318, 319, 666–667 Otitis media, 668–669 acute, 318, 319, 668–669 with allergic rhinitis, 798, 799 bronchiolitis with, 134, 135 chronic, 46 cleft palate and, 199 in Down syndrome, 307 earache in, 318, 319, 668–669

with influenza, 513 mastoiditis with, 574 in measles, 577 with nontuberculous mycobacterial infections, 648 purulent acute, 100 in respiratory syncytial virus, 783 serous, 318 in Turner syndrome, 970 in 22q11.2 deletion syndrome, 266 in Wiskott-Aldrich syndrome, 1020 Otitis media with effusion (OME), 318, 319, 668, 798 Otomycosis, 70, 71 Oto-respiratory reflex, 237 Ototoxicity, in cancer therapy, 147 Ovarian cyst, 2 Ovarian dysgerminomas, 384 Ovarian failure, 44–45, 724, 970, 971 Ovarian germ cell tumors, 384–385 Ovarian insufficiency, premature, 372 Ovarian ischemia, 515 Ovarian mass, 2–3 Ovarian torsion, 2, 3, 68, 243 Ovarian tumors, 12, 68 Ovaries, polycystic. See Polycystic ovarian syndrome Overactive bladder, 107, 262 Overriding aorta, 924 Overuse syndromes, 918–919 Ovotesticular DSD, 38–39 Oxalosis, 194 Oxygen saturation, 1033 Oxygen therapy for altitude sickness, 37 for apnea, 631 for bronchiolitis, 134, 135 for bronchopulmonary dysplasia, 136 for carbon monoxide poisoning, 151 for congestive heart failure, 221 for cor pulmonale, 233 for dyspnea, 315 for hypoplastic left heart syndrome, 488 for influenza, 513

for meconium aspiration syndrome, 581 for patient with single-ventricle physiology, 221 for periodic breathing, 687 for Pneumocystis jiroveci infection, 715 for pneumonia, 717 for pulmonary hypertension, 759 and retinopathy of prematurity, 786, 787 for transient tachypnea of newborn, 955 P Pachygyria, 510 “Packaging” abnormalities, 284, 520 Paget disease of bone, 664 Pain, congenital insensitivity to, 1045 Pain amplification syndrome, 96 Palate, cleft, 198–199, 486, 578 Pallid breath-holding spells, 130 Pallor, 670–671. See also specific disorders causing Pancreas, annular, 518, 578 Pancreatic enzyme replacement therapy, 189, 259, 771 Pancreatic insufficiency, 188, 189, 258, 259 Pancreatic mass, 2–3 Pancreatic pseudocyst, 2, 3, 672–673, 675 Pancreatitis, 674–675 abdominal mass with, 2, 3 acute, 674 in arboviral encephalitis, 1013 ascites in, 68, 674, 675 in Crohn disease, 238 in cryptosporidiosis, 248 in cystic fibrosis, 258 in diabetic ketoacidosis, 293 disseminated intravascular coagulation in, 304 in Epstein-Barr virus infection, 340 fluid collection with, 672 gallstone, 184, 185, 674, 675 intestinal obstruction with, 519 in mumps, 610, 611 portal vein obstruction in, 160 Pancreatoblastoma, 2 PANDAS, 654, 703, 934 Panhypopituitarism, 486

Panic disorder, 860 Panniculitis, 34, 164, 344, 345 Pan-plexus lesions, 116–117 Pansclerotic morphea, 606 Papular purpuric gloves and socks syndrome (PPGSS), 676 Papular urticaria, 748 Paracentesis, 68–69, 692 Paracetamol (acetaminophen) poisoning, 10–11, 20–21, 897, 1067 Paralytic ileus, 518, 519 Paraphimosis, 682, 704–705 Parasacral transcutaneous nerve stimulation, 107, 333 Parasomnias, 140 Parathyroid adenoma, 464 Parathyroid carcinoma, 464 Paratyphoid fever, 812–813 Parental stress, 365 Parenteral nutrition cholelithiasis in, 184, 185 cholestasis in, 632 chronic hepatitis in, 192 hepatomegaly with, 436, 437 for short-bowel syndrome, 847 Paretic strabismus, 882 Parinaud syndrome, 222 Parotitis, 610–611. See also Mumps Paroxysmal cold hemoglobinuria, 90 Paroxysmal nocturnal hemoglobinuria, 425, 1050 Pars defects, 96 Pars sternalis, 296 Partial androgen insensitivity syndrome (PAIS), 38 Partial fetal alcohol syndrome (pFAS), 356–357 Partial seizures, 824–825 Parvovirus B19, 358, 676–677, 849, 952, 1000 Pasteurella, 338, 572, 573 Patau syndrome. See Trisomy 13 Patellofemoral malalignment syndrome, 538–539 Patent ductus arteriosus (PDA), 678–679 aortic coarctation with, 202 congestive heart failure with, 220, 678, 679, 781 Down syndrome and, 306, 678 respiratory distress with, 781

sepsis with, 832 transposition with great arteries with, 956 Patent foramen ovale (PFO), 84, 85, 956 Patent urachus, 656 Pauci-immune glomerulonephritis, 194, 394 Pavlik harness, 285 Pearson syndrome, 1050 Pectus excavatum, 648 Pediculosis, 550–551, 988 Pelizaeus-Merzbacher disease, 1050 Pellagra, 706, 707 Pelvic inflammatory disease (PID), 680–681 chlamydia and, 680, 681, 989 dysuria in, 316 gonococcal infection and, 400, 401, 680, 681, 989 intrauterine devices and, 231, 680 pinworms and, 708 Pemphigus neonatorum, 874 Pendred syndrome, 398, 494, 1050 Penetration, food or fluid, 354 Penile adhesions, 682, 683 Penile curvature, 490, 682 Penile problems, 682–683, 704–705 Penis, ambiguous genitalia and, 38–39 Pentalogy of Cantrell, 924 Peppermint, 531 Peptic ulcer disease, 380–381, 974–975 Perforated appendicitis, 62, 63 Perianal abscess, 690 Perianal cellulitis, 164 Perianal group A β-hemolytic Streptococcus, 294 Periappendicitis, 681 Pericardial effusion, 322, 323 with congestive heart failure, 220, 221 with histoplasmosis, 450 with Kawasaki disease, 537 with mediastinal mass, 583 with metabolic acidosis, 592 with myocarditis, 619 with pericarditis, 684 ventricular tachycardia with, 996

Pericardiocentesis, 685 Pericarditis, 684–685 in congestive heart failure, 220, 221 in histoplasmosis, 450, 451 in lupus erythematosus, 556 in Lyme disease, 558 in measles, 577 in Salmonella infection, 813 in toxoplasmosis, 941 Perichondritis, 318, 319 Perihepatitis, 400, 401, 436, 681 Perinatal brachial plexus palsy, 116–117 Periodic breathing, 686–687, 852 Periodic fever syndromes, 360 Periodontal structures, 1058 Periodontitis, 390–391 Periorbital (preseptal) cellulitis, 164, 222, 688–689, 851 Periorbital edema, 322 Peripheral blood stem cell transplantation (PBSCT), 112 Peripheral hypotonia, 362–363 Peripheral neuroectodermal tumor (PNET), 346 Peripheral vascular disease, with diabetes mellitus, 288 Perirectal abscess, 690–691 Peritoneal abscess, 46, 47 Peritoneal dialysis, peritonitis in, 692 Peritoneal fluid, 68–69 Peritoneal mass, 2–3 Peritonitis, 692–693 anaerobic infection and, 46, 47 ascites with, 69, 322, 323 catheter-related, 148 crying in, 242 intestinal obstruction and, 518, 519 intussusception and, 524, 525 lupus erythematosus and, 556, 692 mesenteric adenitis and, 591 nephrotic syndrome and, 637, 692 omphalitis and, 657 pancreatic pseudocyst and, 672, 673 pelvic inflammatory disease and, 680 portal hypertension and, 730, 731

portal vein obstruction in, 160 Peritonsillar abscess, 46, 318, 319, 622, 694–695, 863, 942 Peritonsillar cellulitis, 164, 694 Periumbilical pain, 6 Periventricular leukomalacia (PVL), 364, 510 Pernicious anemia, 492, 584 Peroxisomal disorders, 192, 362, 363, 592 Persistent depressive disorder, 278–279 Persistent diarrhea, 298 Persistent hypocalcemia, 474 Persistent (chronic) motor or vocal tic disorder, 934 Persistent omphalomesenteric duct, 656 Persistent pulmonary hypertension of the newborn (PPHN), 580, 581, 696–697, 758, 832 Persistent vegetative state, 208 Perthes disease, 92, 698–699 Pertussis, 236, 237, 700–701, 716, 770 Pervasive developmental disorder (PDD), 962 Pes cavus, 562 Pes planus, 372, 538 Petechiae, 138, 358 fever with, 358–359 pallor with, 670 Peters anomaly, 392 Petrositis, 575 Peutz-Jeghers syndrome, 524, 728, 729, 1050 PFAPA syndrome, 622, 623, 880 Pfeiffer syndrome, 1050 PHACES association, 420, 421, 1050 Pharyngeal diphtheria, 300, 301 Pharyngeal dysphagia, 354, 355 Pharyngitis, 702–703 earache with, 319 fever of unknown origin with, 360, 361 gonococcal, 400, 401, 702, 703, 862 herpes simplex, 442, 443, 702 measles, 576 peritonsillar abscess with, 694–695 sore throat with, 862–863 streptococcal, 358, 359, 702–703, 796, 818–819, 862–863 Pharyngoconjunctival fever, 26–27 Phencyclidine (PCP), 892

Phenylketonuria, 282, 510, 1048, 1050 Pheochromocytoma, 2 Phimosis, 682, 683, 704–705 Phonologic/syntactic deficit disorder, 864 Phosphate imbalance. See Hyperphosphatemia; Hypophosphatemia Phosphate supplementation, 485 Phosphoenolpyruvate carboxykinase deficiency, 592 Photoaggravated dermatoses, 706, 707 Photoallergy, 706 Photosensitivity, 706–707, 748 Phototherapy for atopic dermatitis, 83 for hemolytic disease of fetus or newborn, 427 for hereditary spherocytosis, 440 for jaundice, 533, 534, 535 for pruritus, 749 for psoriasis, 753 Phototoxicity, 706 Phrenic nerve injury, 116 Physical abuse, 178–179, 295 Physiologic leukorrhea, 988, 1062 Phytobezoar, 102–103 Phytophotodermatitis, 706 Pica, 102, 360, 544, 602, 670, 1004 PID. See Pelvic inflammatory disease Pierre Robin sequence, 132, 198, 354, 392, 852, 928, 1051 Pierson syndrome, 636 Pillow otalgia, 318 Pilomatrixoma, 622 Pilosebaceous units (PSUs), 12 “Pink tets,” 924 Pinworms, 316, 708–709, 989 Pitting edema, 322 Pituitary apoplexy, 158 Pituitary hormone. See Hypopituitarism Pityriasis rosea, 227 Placental abruption, 304, 426, 626 Plague, 710–711 Plantar warts, 1008 Plaque psoriasis, 752 Plasmapheresis

for autoimmune hemolytic anemia, 91 for glomerulonephritis, 395 for Guillain-Barré syndrome, 409 for lupus erythematosus, 557 for myasthenia gravis, 617 for Stevens-Johnson syndrome/TEN, 879 for thrombotic thrombocytopenic purpura, 425 for urticaria, 983 Plasmodium, 73, 568 Platelet disorders, 8–9. See also Thrombocytopenia; specific disorders Platelet transfusion for bruising in platelet disorders, 139 for dengue infection, 269 for Ebola virus disease, 321 for hemolytic uremic syndrome, 429 for immune thrombocytopenic purpura, 500, 501 for neonatal alloimmune thrombocytopenia, 629 for Wiskott-Aldrich syndrome, 1020 Pleural effusion, 322, 323, 712–713, 1060 with atelectasis, 80 with coccidioidomycosis, 204, 205 with histoplasmosis, 450, 451 with lupus erythematosus, 556 with mediastinal mass, 583 with non-Hodgkin lymphoma, 647 with pancreatic pseudocyst, 672, 673 with pneumonia, 717 Pleurectomy, 713 Pleuritic pain, 712, 718, 756 Pleuritis, in lupus erythematosus, 556 Pleurodesis, 713, 719 Pleuropulmonary infections, anaerobic, 46, 47 Pneumatocele, 717 Pneumococcal vaccine, 73, 358, 549, 574, 688, 830, 848 Pneumocystis carinii. See Pneumocystis jiroveci Pneumocystis jiroveci, 714–715 in HIV infection, 454–455, 714–715 in hyperimmunoglobulinemia E syndrome, 466 in immune deficiency, 498 prophylaxis against, 25, 61, 402, 403, 455, 714, 795, 841, 973 Pneumomediastinum, 293, 701, 719, 781

Pneumonia asthma vs., 74, 75 atelectasis in, 80 bacterial, 716–717 in cat-scratch disease, 157 chlamydia, 180–181, 222, 716 in coccidioidomycosis, 204–205 cough and prevention of, 236 fever of unknown origin in, 360, 361 in HIV (Pneumocystis), 454–455, 714–715 in hyperimmunoglobulinemia E syndrome, 466 with impetigo, 509 influenza, 513 measles, 577 in neonatal sepsis, 832 persistent pulmonary hypertension of newborn in, 696 pertussis, 701, 716 pneumothorax in, 717, 718 rectal prolapse in, 770 in respiratory distress syndrome, 781 in respiratory syncytial virus, 783 in Salmonella infection, 813 in spinal muscular atrophy, 869 in toxoplasmosis, 940, 941 in tracheitis, 943 varicella, 174, 175 in Wiskott-Aldrich syndrome, 1020 Pneumonic plague, 710–711 Pneumonic tularemia, 968 Pneumoparotitis, 611 Pneumoperitoneum, 519, 625 Pneumothorax, 718–719 atelectasis with, 80 chest pain with, 172, 718 with cystic fibrosis, 259, 718 with persistent pulmonary hypertension of newborn, 696 with pertussis, 701 with pneumonia, 717, 718 with respiratory distress syndrome, 781 with tuberous sclerosis, 966 Poikiloderma, 154, 706

Poisoning acetaminophen, 10–11, 20–21, 897, 1067 carbon monoxide, 150–151, 904 child abuse and, 179 food, 370–371, 812–813 heavy metal, 282 iron, 528–529 lead, 282, 496, 516, 519, 544–545, 602, 603 salicylate, 20, 810–811 suicide, 896–897 sympathomimetic, 902–903 toxic alcohols, 936–937 vitamin A, 32, 242, 272, 436, 496, 730 Poland anomaly, 1051 Politzer bag, for barotitis, 98 Pollen-food syndrome, 48, 798 Polyarteritis nodosa, 336, 432, 720–721 Polyarthropathy syndrome, 676 Polyarticular arthritis, 64, 65 Polybrominated diphenyl ethers (PBDEs), 492 Polycystic kidney disease (PKD), 2, 194, 218, 422, 722–723 Polycystic liver disease, 722 Polycystic ovarian syndrome (PCOS), 724–725 abnormal uterine bleeding in, 310 acne in, 12 amenorrhea in, 44, 45, 724 cervicitis vs., 168 congenital adrenal hyperplasia vs., 217 metabolic syndrome in, 598, 724, 725 obesity in, 652, 724 premature adrenarche in, 736, 737 Polycythemia, 726–727 Polycythemia vera, 726 Polymorphous light eruption (PMLE), 706, 707 Polymyositis, 280–281 Polyphagia, 288 Polyps intestinal, 728–729 lower GI bleeding with, 554, 555 nasal, 30, 258, 259, 798 rectal, 770

Polyunsaturated fatty acids, for ADHD, 87 Pompe disease, 362, 363, 1051 Ponseti method, 200–201 Popsicle panniculitis, 164 Pork tapeworm, 914–915 Porphyrias, 706–707, 1051 Portal hypertension, 730–731 in α1-antitrypsin deficiency, 34, 35, 730 ascites in, 68, 730, 731 in biliary atresia, 105 in congenital hepatic fibrosis, 218–219 hepatitis and, 730, 1001 hepatomegaly in, 437, 730 jaundice in, 532 in polycystic kidney disease, 722 in portal vein obstruction, 160, 161 in short-bowel syndrome, 847 in splenic dysfunction, 72 splenomegaly in, 437, 730 upper GI bleeding in, 974–975 Portal pyelophlebitis, 160 Portal vein obstruction, 68, 160–161 Portal vein thrombosis, 730, 930 Portopulmonary hypertension, 730, 731 Portosystemic shunt, 161, 196, 219, 731, 975 Port-wine stains, 420, 421 Postanesthesia hypoventilation, 80 Post enteritis syndrome, 566 Posterior urethral diverticula, 316 Posterior urethral valves (PUV), 262, 462, 463, 732–733 Postexposure prophylaxis, for HIV, 454, 573, 843 Postherpetic neuralgia, 175 Postinfectious glomerulonephritis, 394–395, 422, 423, 509, 746, 819 Postpericardiotomy syndrome, 85, 684, 685 Postthrombotic syndrome, 930 Posttransplant lymphoproliferative disorder (PTLD), 340, 341, 564–565 Posttraumatic stress disorder (PTSD), 147, 178, 843, 892 Postural proteinuria, 746 Potassium imbalance. See Hyperkalemia; Hypokalemia Potassium supplementation, 293, 481 Potter syndrome, 722, 733

Pott puffy tumor, 851 Powassan encephalitis, 1012 Prader-Willi syndrome, 246, 363, 373, 620, 652, 845, 852, 1051 Pragmatic communication disorder, 88 Preadolescent acne, 12 Prebiotics, 239, 299, 847 Precepting, 1028 Precocious puberty, 216–217, 484, 734–735, 736, 737, 738, 739 Prediabetes, 599 Preeclampsia, 304, 592, 725 Preexposure prophylaxis, for HIV, 454 Pregnancy abnormal uterine bleeding in, 310, 311 alcohol in, fetal effects of, 356–357 ectopic, 3, 169, 426, 681 fatty liver of, 592 isotretinoin in, 198 parvovirus B19 in, 677 phenytoin in, 198 prevention of, 228–231 toxoplasmosis in, 940 Turner syndrome and, 971 Zika virus in, 1025 Prehypertension, 472 Premature adrenarche, 736–737 Premature infants abstinence syndrome in, 626 anemia in, 365 apnea in, 132, 630–631 bezoars in, 102 cerebral palsy overdiagnosis in, 167 feeding disorders in, 354 follow-up of NICU graduates, 364–365 intracranial hemorrhage in, 522 necrotizing enterocolitis in, 624–625 omphalitis in, 656 osteopenia in, 365 periodic breathing in, 686 respiratory distress syndrome in, 780–781 retinopathy in, 364, 392, 772, 786–787 Premature ovarian insufficiency (POI), 372

Premature thelarche, 738–739 Premenstrual dysphoric disorder (PDD), 278, 279, 740–741 Premenstrual syndrome (PMS), 740–741 Prepatellar bursitis, 538 Preseptal (periorbital) cellulitis, 164, 222, 688–689, 851 Pressure ulcers, 959 Prevotella, 46 Priapism, 468, 849 Prickly heat, 418 Primary adrenal insufficiency, 742–743 Primary ciliary dyskinesia, 80, 1051 Primary congenital glaucoma (PCG), 392–393 Primary familial and congenital polycythemia (PFCP), 726 Primary pigmented nodular adrenocortical disease (PPNAD), 250 Primary pulmonary hypertension (PPHN), 232 Primary sclerosing cholangitis, 192, 436, 448, 730, 972 Primary snoring, 852 Primum atrial septal defect, 84 Prion disease, 744–745 Probiotics for colic, 207 for Crohn disease, 239 for dental health, 273 for diarrhea, 299 for food poisoning, 371 for functional diarrhea of infancy, 377 for irritable bowel syndrome, 531 for lactose intolerance, 543 for necrotizing enterocolitis, 624 for neonatal sepsis, 833 for rotavirus infection, 809 for seborrheic dermatitis, 823 for short-bowel syndrome, 847 for vaginitis, 989 Problem representation, 1031 Proctitis, 400, 554 Proctocolitis, food protein-induced, 366, 368–369 Progesterone-only contraceptives, 228 Progestin-only contraceptives, 229, 230, 313 Progressive disseminated histoplasmosis (PDH), 450–451 Progressive familial intrahepatic cholestasis (PFIC), 192, 632, 633, 1051

Progressive systemic sclerosis, 606 Prokinetics, 383, 846 Prolactin, elevation of, 44, 45, 146, 410, 486 Prolactinoma, 754 Prolonged unconjugated hyperbilirubinemia (PUH), 534–535 Propionibacterium acnes, 12 Propionic acidemia, 592 Propylthiouracil, 399, 404, 494 Protein C deficiency, 756, 760–761, 778 Protein-energy malnutrition, 570 Protein-losing enteropathy (PLE) bezoars and, 102 cardiac surgery and, 489 edema in, 322, 323 in food allergy, 366, 367 in giardiasis, 389 hypogammaglobulinemia in, 477 in portal vein obstruction, 161 Protein S deficiency, 756, 760–761, 778 Proteinuria, 746–747 with glomerulonephritis, 394, 395, 746, 747 with immunoglobulin A nephropathy, 504, 505 with nephrotic syndrome, 636, 746 with posterior urethral valves, 732, 733 with renal venous thrombosis, 779 with sickle cell disease, 849 with vesicoureteral reflux, 998, 999 Proteus mirabilis, 126, 656 Proton pump inhibitors (PPIs) for eosinophilic esophagitis diagnosis and therapy, 334, 335 for gastritis, 380–381 for gastroesophageal reflux disease, 383 for peptic ulcers, 975 for portal hypertension, 731 for short-bowel syndrome, 846 Provisional tic disorder, 934 Proximal focal femoral deficiency, 1051 Prune belly syndrome, 194, 246, 462, 514, 976, 1051 Pruritus, 748–749 with atopic dermatitis, 82, 748 with biliary atresia, 105

with cutaneous larva migrans, 252 with pinworms, 708 with scabies, 816, 817 with serum sickness, 836, 837 with vaginitis, 988 Pseudoappendicitis syndrome, 1022, 1023 Pseudoataxia, 79 Pseudocyst, pancreatic, 2, 3, 672–673, 675 Pseudogynecomastia, 410, 411 Pseudohemoptysis, 433 Pseudohypocalcemia, 474 Pseudohypokalemia, 480 Pseudohypothyroidism, 844, 1051 Pseudomonas/Pseudomonas aeruginosa in breast abscess, 126 in cystic fibrosis, 258, 259 in neonatal sepsis, 832 in omphalitis, 656 in osteomyelitis, 662, 663 in otitis externa, 666 in otitis media, 668 Pseudoobstruction, intestinal, 225, 846 Pseudopolyps, 728 Pseudostrabismus, 883 Pseudotumor cerebri, 496–497, 652, 653 Psittacosis, 750–751 Psoas abscess, 789 Psoas sign, 62 Psoralen plus ultraviolet A, 403, 607, 753 Psoriasis, 294, 748, 752–753 Psoriasis vulgaris, 226, 752, 822 Psoriatic arthritis, 64, 752, 872–873 Psychosocial disorders, cancer therapy and, 147 PTEN macrocephaly/fusion, 1051 Pubertal delay, 754–755, 844–845 Puberty adrenal insufficiency and, 743 cancer therapy and, 147 cystic fibrosis and, 258 growth hormone deficiency and, 406–407 gynecomastia in, 410–411

hypopituitarism and, 486, 487 hypothyroidism and, 492, 493 precocious, 216–217, 484, 734–735, 736, 737, 738, 739 transgender youth and, 950–951 Turner syndrome and, 970–971 weight loss and, 1010 Pubic lice, 550–551, 988 Pulmonary artery, anomalous left coronary artery from, 54–55 Pulmonary aspergillosis, 70, 71 Pulmonary atresia, 266, 956 Pulmonary blastomycosis, 108, 109 Pulmonary edema, 322–323 in diabetic ketoacidosis, 293 high-altitude, 36–37 in toxic shock syndrome, 939 in tracheitis, 943 Pulmonary embolism, 80, 232, 432, 756–757, 930–931, 959 Pulmonary fibrosis, in systemic sclerosis, 914 Pulmonary hemorrhage, 781 Pulmonary hemosiderosis, 432, 433 Pulmonary hypertension, 758–759 in biliary atresia, 105 in bronchopulmonary dysplasia, 136, 137 in congenital diaphragmatic hernia, 296, 297 cor pulmonale in, 232 in cystic fibrosis, 259 hemoptysis in, 432 in hereditary spherocytosis, 441 in obstructive sleep apnea, 853 persistent, of newborn, 580, 581, 696–697, 758, 832 primary, 232 in sickle cell disease, 849 in thalassemia, 927 Pulmonary hypoplasia, 462, 696, 732, 733 Pulmonary infarction, 756 Pulmonary interstitial emphysema, 781 Pulmonary sequestration, 432 Pulmonary toxicity, in cancer therapy, 147 Pulmonary vascularity, 1041 Pulpitis, 274–275 Pulse dye laser, 421

Pulse oximetry, 1033–1038 Pulsus paradoxus, 684, 685 Pure red cell aplasia, 676 Purpura, 358–359 Purpura fulminans, 304, 760–761, 931 Purulent acute otitis media, 100 Pustular psoriasis, 752 Pustulosis, 12 Pyelonephritis, 762–763, 978–979 acute, 762, 763 in candidiasis, 149 chronic, 762, 763 dysuria in, 316, 317, 762 hematuria in, 422–423 in polycystic kidney disease, 723 in Salmonella infection, 813 Pyelophlebitis, 160 Pyloric stenosis, 518, 519, 764–765, 1004 Pyloromyotomy, 765 Pyoderma. See Impetigo Pyoderma gangrenosum, 238 Pyogenic granuloma, 420 Pyridoxine, for toxic alcohol poisoning, 937 Pyridoxine-dependent seizures, 510, 511, 593, 634 Pyropoikilocytosis, 425 Pyruvate carboxylase deficiency, 592 Pyruvate dehydrogenase deficiency, 510, 592, 593 Pyuria, sterile, 762 Q Q fever, 360, 361 QT interval prolongation, 552–553, 996, 997 Quinsy. See Peritonsillar abscess R Rabies, 326, 572, 573, 766–767 Rabies vaccine, 767 Radial head subluxation, 768–769 Radiation-induced gastritis, 380 Radiation pneumonitis, 80 Radiation therapy for brain tumors, 123

edema in, 322 for Ewing sarcoma, 347 for histiocytosis, 449 for Hodgkin lymphoma, 453 late effects of, 146–147 for mediastinal mass, 583 for neuroblastoma, 641 for non-Hodgkin lymphoma, 647 for Wilms tumor, 1017 Radioactive iodine, 399, 405 Ramsay Hunt syndrome, 100–101, 319, 666 Ramstedt procedure, 765 Ranula, 622 Rapidly involuting congenital hemangioma (RICH), 420 Rapunzel syndrome, 102 Rashkind procedure, 957 Rastelli procedure, 957 Raynaud phenomenon, 146, 394, 556, 606, 912–913 RDS. See Respiratory distress syndrome Reactive airway disease (RAD), 236–237, 581 Reactive arthritis, 222, 257, 316, 370, 872–873, 1023 Reactive hyperplasia, 590, 622 Rebound headache, 417 Receptive language disorders, 864, 866 Rectal atresia, 507 Rectal polyps, 770 Rectal prolapse, 258, 259, 770–771 Rectal ulcer syndrome, 771 Rectoperineal fistula, 507 Rectourethral fistula, 506, 507 Rectovestibular fistula, 506 Recurrent respiratory papillomatosis (RRP), 456–457 Red Man syndrome, 49 Reentry tachycardia, 900, 901 Refeeding syndrome, 56, 57, 353, 481, 571 Reflective modeling, 1028 Reflex sympathetic dystrophy, 563 Refractive amblyopia, 40, 773 Refractive error, 772–773, 1056 in fragile X syndrome, 372, 373 in NICU graduates, 364

in retinopathy of prematurity, 787 strabismus with, 772, 773, 882, 883 in Turner syndrome, 970 Refractory cytopenia of childhood (RCC), 60 Regurgitation, 1004 Renal agenesis, 506, 976 Renal arterial thrombosis, 422 Renal artery hypoplasia, 774 Renal artery stenosis, 774–775 Renal atrophy, 779 Renal cell carcinoma (RCC), 2 Renal dysplasia/hypoplasia, 194, 608, 733 Renal graft rejection, 424 Renal mass, 2–3 Renal replacement therapy (RRT). See also Dialysis for acute kidney injury, 19 for Ebola virus disease, 321 for hemolytic uremic syndrome, 429 for rhabdomyolysis, 793 Renal scarring, 979, 998 Renal toxicity, in cancer therapy, 147 Renal tubular acidosis, 776–777 Renal venous thrombosis (RVT), 2, 422, 778–779, 930 Reproductive toxicity, in cancer therapy, 147 Resistance, vascular, 994, 995, 1042 Resonance disorders, 866 Resorption atelectasis, 80 Respiratory distress with meconium aspiration, 580–581 with mediastinal mass, 582, 583 in persistent pulmonary hypertension of newborn, 696 in pleural effusion, 713 in pneumothorax, 718, 719 in pulmonary embolism, 756 in respiratory syncytial virus, 782 in severe acute respiratory syndrome, 838–839 in sore throat, 863 in spinal muscular atrophy, 868, 869 in tetanus, 923 in tracheitis, 942, 943 in transient tachypnea of newborn, 954–955

in wheezing, 1015 Respiratory distress syndrome (RDS), 780–781 bronchopulmonary dysplasia in, 136, 781 cor pulmonale in, 232 disseminated intravascular coagulation in, 304 sepsis and, 830, 831 Respiratory events related to arousals (RERA), 852 Respiratory syncytial virus (RSV), 30, 74, 134–135, 240, 716, 782–783 Restrictive cardiomyopathy (RCM), 152–153, 220 Restrictive strabismus, 882 Retained fetus, 304 Retching, 1004 Reticulocytosis, 397 Retinal detachment, 772, 787 Retinitis, 157, 260 Retinitis pigmentosa, 1051 Retinoblastoma, 164, 392, 784–785 Retinopathy, diabetic, 288, 291 Retinopathy of prematurity (ROP), 364, 392, 772, 786–787 Retractile testes, 246, 247 Retropharyngeal abscess, 319, 622, 623, 694, 788–789 Rett syndrome, 130, 1051 Return to school or day care in appendicitis, 63 in chickenpox, 175 in conjunctivitis, 223 in cryptosporidiosis, 249 in hand, foot, and mouth disease, 413 in impetigo, 509 in influenza, 513 in lice, 551 in mumps, 611 in parvovirus B19 infection, 677 in pinworms, 709 in roseola, 807 in rotavirus infection, 809 in Salmonella infection, 813 in scabies, 817 in scarlet fever, 818, 819 in stomatitis, 881 in streptococcal pharyngitis, 702

in tinea capitis, 33 in viral hepatitis, 1000 Rex shunt, 161 Reye syndrome, 20, 417, 513, 790–791, 810, 1025 Rhabdoid tumor, 122 Rhabdomyolysis, 792–793 acute kidney injury in, 18, 19, 792–793 acute liver failure in, 20 factitious hematuria in, 422, 423, 792, 793 in heat illness, 419 in influenza, 513 potassium imbalance in, 480, 481, 792, 793 in status epilepticus, 876 in tetanus, 923 Rhabdomyoma, 966, 967 Rhabdomyosarcoma, 164, 623, 794–795 Rheumatic fever, 796–797, 819 fever of unknown origin in, 360, 361 with impetigo, 509 leukocytosis in, 548 Rheumatic heart disease, 220, 796–797 Rheumatic spondyloarthropathy, 872–873 Rheumatoid arthritis, 64–65. See also Juvenile idiopathic arthritis diabetes mellitus with, 288 splenic function in, 72 Rheumatoid factor, 64 Rh immunoglobulin, 426, 501 Rh incompatibility, 426–427 Rhinitis, allergic, 30–31, 798–799 asthma with, 74, 798 cough with, 236, 237 earache with, 319 food allergy with, 366 nosebleeds with, 650 sinusitis with, 799, 850, 851 Rhinitis sicca, 650 Rhinocerebral mucormycosis, 293 Rhinoconjunctivitis, 502 Rhinosinusitis, 70, 71, 850 Richter hernia, 514 Rickets, 800–801, 1065

back pain with, 96 with chronic hepatitis, 192, 193 with chronic kidney disease, 194 hypocalcemic, 474, 800–801 hypophosphatemic, 484–485, 800–801 with renal tubular acidosis, 776, 777 short stature with, 844 Rickettsial disease, 802–803. See also specific diseases encephalitis in, 326, 327 fever and petechiae in, 358, 359 Rickettsialpox, 802 Right lower quadrant pain, 6 Right upper quadrant pain, 6 Right ventricular failure, 232–233 Right ventricular hypertrophy, 924–925 Right ventricular outflow tract obstruction (RVOTO), 924–925 Risus sardonicus, 922 Ritter disease, 874 Rocky Mountain spotted fever (RMSF), 304, 360, 361, 802–805 Romano-Ward syndrome, 552 Rombo syndrome, 604, 605 ROP. See Retinopathy of prematurity Rosacea, ocular, 110 Rosai-Dorfman disease, 448, 564–565, 623 Roseola, 806–807 Rotavirus, 808–809, 840 Rotavirus vaccine, 808, 809, 985 Rothmund-Thomson syndrome, 664, 706 Rotor syndrome, 1051 Roundworms, 66–67, 252–253, 708–709 Rovsing sign, 62 RSA1 syndromes, 1051 RSV. See Respiratory syncytial virus Rubella, 386–387 Bell palsy with, 100 congenital, 386–387, 516, 678 developmental delay with, 282 fetal syndrome, 1046 glaucoma in, 392 hepatitis with, 1000 Rubella vaccine, 386

Rubeola. See Measles (rubeola) Rubinstein-Taybi syndrome, 392, 1051 Rumack-Matthew nomogram, 10–11 Runaway status, chronic, 178 Russell-Silver syndrome, 1051 S Sacral agenesis, 506 Sacrococcygeal teratoma, 2, 384, 385 Sagittal sinus thrombosis, 851 St. Louis encephalitis, 1012 Salicylate poisoning, 20, 810–811 Salivary adenitis, 610, 611 Salivary calculi, 610, 611 Salmonella infections, 370–371, 812–813, 1063 breast abscess with, 126 fever of unknown origin with, 360, 361 osteomyelitis with, 662, 663, 813 septic arthritis in, 834, 835 Salmon patches, 420, 421 Salpingitis, 680. See also Pelvic inflammatory disease Sand flies, 1012 Sandhoff disease, 1051 Sandifer syndrome, 382, 510, 876 Sanfilippo syndrome, 1049 SAPHO syndrome, 12 Sarcoidosis, 814–815 Bell palsy in, 100 epididymitis in, 336 erythema nodosum in, 344, 345, 815 fever of unknown origin in, 360, 361 Guillain-Barré syndrome in, 408 hemoptysis in, 432 hypercalcemia in, 464 splenic function in, 72 Sarcoma botryoides, 316, 317 Sarcoptes scabiei, 816 SARS. See Severe acute respiratory syndrome SBE. See Subacute bacterial endocarditis Scabies, 226, 295, 748, 816–817 Scalded skin syndrome, staphylococcal, 874–875 Scalp abscess, gonococcal, 400

Scapular winging, 116, 117, 614 Scarf sign, 362 Scarlet fever, 509, 702, 818–819, 862 Scarring, acne and, 12–15 Scheie syndrome, 1049 Scheuermann disease, 96, 97, 820 Schistosomiasis, 68 Schizencephaly, 510 Schizophrenia, 88, 266, 267 School, return to. See Return to school or day care Schwannoma, 122 Scleritis, 222 Sclerocornea, 392 Sclerodactyly, 606, 913 Scleroderma localized (morphea), 606–607 systemic, 912–913 Sclerosing cholangitis in biliary atresia, 104 cirrhosis with, 196, 197 in Crohn disease, 238 in cryptosporidiosis, 248 hepatitis with, 192 hepatomegaly with, 436 in histiocytosis, 448, 449 jaundice with, 532 neonatal cholestasis with, 632, 633 portal hypertension with, 730 in ulcerative colitis, 972 Scoliosis, 820–821 in cancer therapy, 146 congenital, 928 in developmental dysplasia of hip, 284, 285 in diskitis, 303 in fragile X syndrome, 372 in hyperimmunoglobulinemia E syndrome, 466 in muscular dystrophy, 614, 615 in neurofibromatosis, 642 in nontuberculous mycobacterial infections, 648 in osteogenesis imperfecta, 661 in short stature, 844

in spinal muscular atrophy, 869 in thoracic insufficiency syndrome, 928–929 in 22q11.2 deletion syndrome, 266 Scombroidosis, 49 Scrapie, 744 Scrotal edema, 322, 323 Scrotum acute, 336 bifid, 38 Scrub typhus, 802 Scuba diving, ear pain in, 98–99, 318 Sealants, dental, 273 Sebaceous gland hyperplasia, 604 Seborrheic dermatitis, 110, 226, 294, 822–823 Seckel syndrome, 1051 Second-impact syndrome, 215 Secretory diarrhea, 188, 298 Secundum atrial septal defect, 84 Sedative-hypnotic withdrawal, 16–17 Seizures in brain vascular lesions, 992, 993 in breath-holding spells, 130, 131 in Campylobacter infection, 145 in carbon monoxide poisoning, 151 in coma, 208, 209 developmental delay in, 282 in diabetes insipidus, 287 in Down syndrome, 306 in drowning, 308, 309 in encephalitis, 326, 327, 1013 febrile, 826–827 in floppy infant syndrome, 362, 363 in fragile X syndrome, 373 in hemolytic uremic syndrome, 429 in hypocalcemia, 475 in hyponatremia, 482, 483, 825 in hypopituitarism, 487 intellectual disability with, 516, 517 in intracranial hemorrhage, 522, 523 in lead poisoning, 544, 545 in muscular dystrophy, 614

in neonatal abstinence syndrome, 626 in neonatal encephalopathy, 634 in neonatal sepsis, 832 in NICU patients, 364 partial and generalized, 824–825 pyridoxine-dependent, 510, 511, 593, 634 in Reye syndrome, 790 in rickets/osteomalacia, 801 in roseola, 807 in rotavirus infection, 809 in SIADH, 907 speech delay with, 864 speech problems with, 867 in status epilepticus, 876–877 in stroke, 887 in subdural hematoma, 890, 891 in syncopal spells, 905 thrombosis with, 930 in tuberous sclerosis, 966, 967 in 22q11.2 deletion syndrome, 266, 267 Selective mutism, 88, 860, 867 Selective serotonin reuptake inhibitors (SSRIs) for cataplexy, 621 for depression, 279 for excoriation disorder, 349 for fragile X syndrome, 373 for obsessive-compulsive disorder, 654, 655 for premenstrual syndrome, 741 for separation anxiety disorder, 829 for social anxiety disorder, 860, 861 for stereotypic movement disorder, 415 suicide risk with, 741, 829, 861, 897 for trichotillomania, 962 withdrawal from, 16–17 Self-injury, 88, 89, 414, 516 Senior-Loken syndrome, 772 Sensory strabismus, 882, 883 Sentinel event, and neonatal encephalopathy, 634 Separation anxiety disorder, 828–829 Sepsis, 830–831 bruising in, 138, 139

in candidiasis, 148, 149 disseminated intravascular coagulation in, 304 in Ebola virus disease, 321 edema in, 322 fever and petechiae in, 358, 359 in group A β-hemolytic Streptococcus infection, 885 intra-abdominal, 160 in intussusception, 525 in meningococcemia, 588 in necrotizing enterocolitis, 624, 625 neonatal, 832–833 in NICU patients, 364 in omphalitis, 657 in periorbital cellulitis, 689 persistent pulmonary hypertension of newborn in, 696 in pneumonia, 717 postsplenectomy, 441 in purpura fulminans, 760 in respiratory distress syndrome, 781 in rotavirus infection, 809 in sickle cell disease, 849 in transfusion reaction, 948–949 in Wiskott-Aldrich syndrome, 1020 Sepsis syndrome, 58 Septate vagina, 506 Septic arthritis, 92, 509, 663, 834–835 Septic cavernous sinus thrombosis, 158–159 Septicemia, 127, 943 Septicemic plague, 710–711 Septic shock, 48, 830–831 Septo-optic dysplasia, 406, 486 Sequestration crises, 72 Serotonin syndrome, 902 Serous otitis media, 318 Serrated polyposis syndrome, 728 Serratia marcescens, 422, 423, 432 Serum sickness, 836–837 Serum sickness-like reactions, 836, 837 Severe acute respiratory syndrome (SARS), 838–839 Severe aplastic anemia (sAA), 60 Severe combined immunodeficiency (SCID), 498–499, 840–841

Severe sepsis, 830 Sex trafficking, 178 Sexual abuse, 178, 842–843 anogenital warts in, 1009 chlamydia in, 180, 842–843 diaper dermatitis vs., 295 dysuria in, 316, 317 eating disorders in, 142 gonococcal infections in, 400, 401, 842–843 HPV infection in, 457 pharyngitis in, 702 syphilis in, 842–843, 910 Sexual development, disorders of, 38–39, 217, 246 Sexualized behaviors, 842 Sexually transmitted infections (STIs). See also specific infections cervicitis in, 168–169 dysuria in, 316, 317 epididymitis in, 336, 337 sexual abuse and, 842–843 vaginitis in, 988–989 Shagreen patches, 966 Shiga toxin-producing Escherichia coli (STEC), 428–429, 1063 Shigella, 370–371, 548, 826, 989, 1063 Shigella dysenteriae, 428 Shingles, 174–175 Shock in allergic child, 30 anaphylactic, 48, 49 cold, 830, 831 dengue, 269 disseminated intravascular coagulation in, 304 hypovolemic, 433 in iron poisoning, 528, 529 in lower GI bleeding, 554 in meningococcemia, 588, 589 in necrotizing enterocolitis, 624, 625 in pleural effusion, 713 septic, 48, 830–831 toxic (See Toxic shock syndrome) Short-acting β2 agonists (SABAs), 75–76 Short-bowel syndrome, 188, 239, 298, 519, 625, 846–847, 1003

Short-rib thoracic dysplasia, 1051 Short stature, 844–845 in hypophosphatemia, 484 in hypopituitarism, 487, 844 in osteogenesis imperfecta, 660, 661 in precocious puberty, 735 in Turner syndrome, 844, 845, 970, 971 SHORT syndrome, 464 Shunts Blalock-Taussig systemic-to-pulmonary artery, 925 for hydrocephalus, 461, 639 malfunctioning, 461 portosystemic, 161, 196, 219, 731, 975 Rex, 161 splenorenal, 731 ventriculoperitoneal, 461, 639, 876, 993 ventriculosubgaleal, 461 Shwachman-Diamond syndrome, 22, 644, 645, 1051 SIADH. See Syndrome of inappropriate antidiuretic hormone secretion Sialadenitis, 319 Sicca syndrome, 913 Sick euthyroid syndrome, 494 Sickle cell disease, 848–849 avascular necrosis in, 92, 848, 849 back pain in, 96 chest pain in, 172 Chlamydophila pneumoniae in, 183 cholelithiasis in, 184, 185 epiglottitis in, 338 G6PD deficiency and, 397 hematuria in, 422, 423 hemolysis in, 424, 425 intracranial hemorrhage in, 522 leukocytosis in, 548, 549 osteomyelitis in, 662, 663 septic arthritis in, 834, 835 splenic function in, 72, 73, 848, 849 splenic mass in, 2 stroke in, 848, 849, 886, 887 thrombosis in, 930 Sickle cell trait, and malaria, 568

Sideroblastic anemia, 602 Sigmoid volvulus, 225 Silk glove sign, 514 Silver nitrate cautery, 651 Simpson-Golabi-Behmel syndrome, 52 Singultus (hiccups), 444–445 Sinus histiocytosis, 623 Sinusitis, 850–851 with allergic rhinitis, 799, 850, 851 with anaerobic infection, 46 with aspergillosis, 70, 71 with asthma, 75 cough in, 236 with cystic fibrosis, 258, 259 with Down syndrome, 307 earache in, 319 fever of unknown origin in, 361 idiopathic cavernous, 158, 159 with influenza, 513 Sinusoidal obstruction syndrome (SOS), 113, 730 Sinus pericranii, 992 Sinus venosum atrial septal defect, 84 Sjögren syndrome, 72, 162, 610, 611 Skeletal dysplasia, 460, 844, 845 Skin picking disorder, 348–349 Skin prick testing, 367 SLE. See Lupus erythematosus Sleep apnea, 852–853. See also Obstructive sleep apnea syndrome Sleep bruxism, 140 Sleep disorders. See also specific disorders in ADHD, 86 in autism spectrum disorder, 88, 89 in fragile X syndrome, 372, 373 in polycythemia, 726 Sleep paralysis, 620 Sleep rhythmic disorder, 414 Sliding hernia, 514 Slipped capital femoral epiphysis (SCFE), 92, 487, 652, 653, 854–855 Smallpox, 856–857 Smallpox vaccine, 856, 857 Smith-Lemli-Opitz syndrome, 52, 198, 363, 446, 1051

Smoke inhalation, 80 Snake bite, 858–859 SNAPPS presentation method, 1028 Snoring, primary, 852 SOAP feedback, 1030 Social anxiety disorder, 828, 829, 860–861 Social communication disorder, 89 Sodium imbalance. See Hypernatremia; Hyponatremia Sodium supplementation, 217, 483, 907 Soft tissue infections, 46 Solar urticaria, 706, 707 Somatization disorders, 278 Sore throat, 862–863 Sotos syndrome, 372, 1051 Spasmodic croup, 240 Spasms, infantile, 510–511, 966, 967 Spastic cerebral palsy, 166 Specific language impairment (SLI), 864 Spectrin deficiency, 440 Speech and language therapy, 865, 889 Speech delay, 798, 864–865 Speech problems, 866–867 Speech programming deficit disorder, 864 Spermicidal agents, 229, 230 Spherocytosis, hereditary, 2, 424, 425, 440–441 Spider bites, 858–859 Spina bifida, 282, 638–639 Spinal cerebellar ataxia, 1051 Spinal cord compression, 22, 23, 583, 616 Spinal cord tethering, 506, 638, 820, 928 Spinal muscular atrophy (SMA), 362, 363, 868–869 atelectasis in, 80 botulism vs., 114–115 Spinal muscular atrophy with respiratory distress (SMARD), 868 Spinocerebellar ataxias (SCAs), 78 Spirochetes, 46 Spirometry in acute chest syndrome, 849 in allergic child, 31 in asthma, 75 in atelectasis, 80, 81

in bronchopulmonary dysplasia, 136 in cough evaluation, 237 in diaphragmatic hernia, 297 in dyspnea, 315 in wheezing evaluation, 1015 Splenectomy for autoimmune hemolytic anemia, 91 for hereditary spherocytosis, 440, 441 for immune thrombocytopenic purpura, 139, 501 peritonitis with, 692 for splenomegaly, 871 for thalassemia, 927 for Wiskott-Aldrich syndrome, 1020 Splenic artery occlusion, 72 Splenic cyst, 2 Splenic malformation syndrome, 533 Splenic mass, 2–3 Splenic rupture, 341, 568 Splenic sequestration, 848, 849 Splenic vein thrombosis, 72, 160, 730 Splenomegaly, 72, 870–871 abdominal masses and, 2–3 ascites and, 68 atelectasis with, 80 chronic hepatitis and, 192, 193 cirrhosis and, 196, 197 common variable immunodeficiency and, 210 cystic fibrosis and, 258, 259 cytomegalovirus infection and, 260 Epstein-Barr virus infection and, 340, 341 hemolysis and, 424 hemolytic disease of fetus or newborn and, 426 in Hodgkin lymphoma, 452 hyponatremia and, 482 immune thrombocytopenic purpura and, 500 jaundice with, 532 malaria and, 568 measles and, 576 metabolic acidosis and, 592 microcytic anemia and, 602 myocarditis and, 618

with neck masses, 622 neonatal cholestasis and, 632 with pallor, 670 portal hypertension and, 437, 730 portal vein obstruction and, 160, 161 psittacosis and, 750 rickettsial disease and, 802 Salmonella infection and, 812 sarcoidosis and, 814 serum sickness and, 836 sickle cell disease and, 72, 848, 849 thalassemia and, 926 in transposition of great arteries, 956 tuberculosis and, 964 with tularemia, 969 22q11.2 deletion syndrome and, 266 Splenorenal shunt, 731 Spondyloarthropathy, 872–873 Spondyloepiphyseal dysplasia, 1052 Spondylolisthesis, 96, 97, 820 Spondylolysis, 96, 97, 820 Spondylothoracic dysplasia, 928 Spontaneous bacterial peritonitis (SBP), 69, 322, 323, 637, 692–693, 730, 731 Spontaneous intestinal perforation (SIP), 625 Sports concussion in, 120–121, 214–215 dental trauma in, 276 von Willebrand disease and, 1006, 1007 warfarin use and, 757 SSRIs. See Selective serotonin reuptake inhibitors Staphylococcal food poisoning, 370, 1063 Staphylococcal scalded skin syndrome, 874–875 Staphylococcus aureus in atopic dermatitis, 83 in breast abscess, 126 in cellulitis, 164–165, 688, 689 in cervical adenitis, 623 in cystic fibrosis, 258, 259 in diaper rash, 294, 295 in food poisoning, 370, 1063 in impetigo, 508, 509

in lymphadenitis, 561 methicillin-resistant (See Methicillin-resistant Staphylococcus aureus) in neonatal sepsis, 832 in omphalitis, 656, 657 in osteomyelitis, 662, 663 in otitis externa, 666 in otitis media, 668 in peritonsillar abscess, 694, 695 in pneumonia, 716, 717 in retropharyngeal abscess, 788, 789 in scalded skin syndrome, 874–875 in scarlet fever, 818 in toxic shock syndrome, 938–939 in tracheitis, 942, 943 Stargardt disease, 1052 Statins, 195, 471, 557, 599, 637 Status epilepticus, 327, 825, 826, 827, 876–877 Status migrainosus, 417 Steatorrhea, 188, 298, 299 with bezoars, 103 with cystic fibrosis, 259 with giardiasis, 388, 389 with megaloblastic anemia, 584 with portal vein obstruction, 161 with rickets/osteomalacia, 800 STEC. See Shiga toxin-producing Escherichia coli Stem cell transplantation, 112–113 for acute myeloid leukemia, 25 for aplastic anemia, 60–61 for chronic granulomatous disease, 191 donor selection in, 112 graft-versus-host disease in, 402–403 for hyperimmunoglobulinemia E syndrome, 467 for immune deficiency, 499, 840 late effects of, 146–147 for lymphoproliferative disorders, 565 for neuroblastoma, 641 for neutropenia, 645 for sickle cell disease, 849 for thalassemia, 927 for Wiskott-Aldrich syndrome, 1020–1021

Stereotypic movement disorder (SMD), 414, 415 Stereotypies, 88, 414, 934 Sterile pyuria, 762 Sternocleidomastoid (pseudo) tumor of infancy, 622, 623 Stevens-Johnson syndrome (SJS), 222, 316, 342, 343, 412, 878–879, 880 Stickler syndrome, 198, 392, 772, 1052 Stiff man syndrome, 923 Stiff skin syndrome, 1052 STIs. See Sexually transmitted infections Stomach mass, 2–3 Stomatitis, 880–881 earache with, 318, 319 herpetic gingivostomatitis, 390, 412, 442 in iron deficiency, 526 magic mouthwash for, 413 vesiculoulcerative, 412–413 Stones (calculi). See Cholelithiasis; Nephrolithiasis; Urolithiasis Stool softeners, 225, 329, 771 Strabismic amblyopia, 40 Strabismus, 882–883 with congenital glaucoma, 392, 393 with Down syndrome, 306 with fragile X syndrome, 372, 373 with neural tube defects, 639 in NICU graduates, 364 with refractive error, 772, 773, 882, 883 with retinoblastoma, 784 with retinopathy of prematurity, 787 with Turner syndrome, 970, 971 Streptococcal infections, 884–885. See also specific infections glomerulonephritis after, 394–395, 422, 423, 509, 819 meningitis, 586, 587 neonatal sepsis, 832, 833 omphalitis, 656 osteomyelitis, 662 otitis media, 668 pediatric autoimmune neuropsychiatric associated with (PANDAS), 654, 703, 934 pelvic inflammatory disease, 680 periorbital cellulitis, 688 peritonsillar abscess, 622, 694, 695 pneumonia, 716

in respiratory distress syndrome, 781 retropharyngeal abscess, 788, 789 rheumatic fever, 796–797 scarlet fever, 818–819 septic arthritis, 834, 835 toxic shock syndrome, 819, 884, 885, 943 vaginitis, 989 Streptococcal pharyngitis, 358, 359, 702–703, 797, 818–819, 862–863 Stress hyperglycemia, 292 Stress incontinence, 332 Stress test, 173 Stridor, 946, 1014 with croup, 240–241 crying with, 242 with dyspnea, 314 with laryngomalacia, 946 with lymphadenopathy, 561 with mediastinal mass, 582 with retropharyngeal abscess, 788 with tracheitis, 942 with tracheomalacia, 946 Stroke, 886–887 developmental delay with, 282 hemorrhagic, 522–523, 886 infantile spasms in, 510 ischemic, 886–887, 930 metabolic, 592, 595 neonatal encephalopathy and, 635 in NICU patients, 364 polyarteritis nodosa and, 721 sickle cell disease and, 848, 849, 886, 887 in sympathomimetic poisoning, 903 Strongyloides stercoralis, 66 Structured clinical observation (SCO), 1028, 1029 Student clinical observation of preceptor (SCOOP), 1028 Stunting, 570, 571 Stupor, 208 Sturge-Weber syndrome, 392, 992–993, 1052 Stuttering, 888–889 Subacute bacterial endocarditis (SBE), 330–331. See also Endocarditis Subacute sclerosing panencephalitis (SSPE), 577

Subarachnoid hemorrhage, 522–523, 775, 890 Subclavian artery, aberrant, 306 Subclavian artery disease, cancer therapy and, 146 Subclinical hypothyroidism, 492, 493 Subcutaneous fat necrosis (SCFN), 464 Subdural abscess, 851 Subdural empyema, 46 Subdural hematoma, 242, 522, 890–891 Subependymal giant cell astrocytomas (SEGAs), 966, 967 Subependymal nodules, 966, 967 Subglottic allergic edema, 240 Subglottic stenosis, 137, 943 Submersion injury, 308 Suboptimal intake jaundice (SIJ), 534–535 Subperiosteal abscess, 851 Subsequent neoplasms, cancer therapy and, 147 Substance abuse, 892–893. See also Acute drug withdrawal alcohol intoxication and, 29 anorexia nervosa and, 56 depression in, 278 endocarditis in, 330 excoriation in, 348 intracranial hemorrhage in, 522 sexual abuse and, 843 transgender youth and, 950 trichotillomania with, 962 ventricular tachycardia in, 996 Substance use disorder, 892–893 Sudden cardiac death, 552, 553, 618, 619, 925, 997 Sudden infant death syndrome (SIDS), 894–895 brief resolved unexplained event and, 132, 133 long QT syndrome and, 552 neonatal apnea and, 631 periodic breathing and, 686, 687 Sudden unexpected deaths in infancy (SUDI), 894 Sudden unexpected infant deaths (SUID), 894 Sudden unexplained death in epilepsy patients (SUDEP), 825 Suicide, 896–897 acne and, 12, 14, 15 anorexia nervosa and, 57 antidepressants and, 655, 861, 897

antiepileptics and, 825 depression and, 278–279 SSRIs and, 741, 829, 861, 897 substance use disorders and, 893 transgender youth and, 950 Sulfhemoglobinemia, 600 Sulfite oxidase/molybdenum cofactor deficiency, 362 Sun exposure, 706–707 Sunscreen, 707 Superficial thrombophlebitis, 164 Superior mediastinal syndrome (SMS), 646, 647 Superior mesenteric artery (SMA) syndrome, 518, 519, 898–899 Superior vena cava (SVC) syndrome, 930 with acute lymphoblastic leukemia, 22, 23 edema with, 322 with histoplasmosis, 450, 451 with mediastinal mass, 582, 583 with non-Hodgkin lymphoma, 646, 647 Suppurative lymphadenitis, 509 Supralevator abscess, 690 Supraventricular tachycardia (SVT), 242, 243, 900–901 Surfactant deficiency, 80, 237, 364, 696, 780 Surfactant therapy, 581, 780, 781 Survivors, late effects of cancer therapy in, 146–147 Swimmer’s ear, 666 Swyer syndrome, 384 Sydenham chorea, 796 Sympathomimetic poisoning, 902–903 Syncope, 904–905 in breath-holding spells, 130, 905 in carbon monoxide poisoning, 150, 151 cough, in pertussis, 701 in heart disease, 173 heat, 418, 419 in long QT syndrome, 552, 553 in pulmonary embolism, 756 in pulmonary hypertension, 758 Syndrome of inappropriate antidiuretic hormone secretion (SIADH), 118, 119, 482–483, 581, 587, 906– 907 Synovitis, transient, 908–909 Syphilis, 910–911

Bell palsy in, 100 cervicitis in, 168 chancroid coinfection with, 170, 442 fever of unknown origin in, 360, 361 hepatomegaly in, 436, 437 meningitis in, 586 sexual abuse and, 842–843, 910 Syringomyelia, 638–639 Systemic inflammatory response syndrome (SIRS), 674, 830 Systemic juvenile idiopathic arthritis, 64 Systemic lupus erythematosus (SLE). See Lupus erythematosus Systemic sclerosis, 912–913 T Tache noire, 802 Tachycardia. See also specific conditions causing in cardiomyopathy, 152–153, 901, 996 in congestive heart failure, 220, 901 in cor pulmonale, 232 in hypoplastic left heart syndrome, 488 supraventricular, 242, 243, 900–901 Tachypnea. See also specific conditions causing transient, of newborn, 584, 954–955 Taenia saginata, 914 Taeniasis, 915 Taenia solium, 914 Takayasu arteritis, 774 Takeuchi procedure, 55 Talc, for pleurodesis, 713, 719 Talipes equinovarus (clubfoot), 200–201, 638 Tanner stages, 44, 406, 754 Tapeworm, 914–915 Tay-Sachs disease, 1052 T-cell defects, 498–499 T-cell lymphoma, 163, 646 Tea tree oil, 15, 551, 823 Teeth cancer therapy and, 147 care of, 272–273 caries in, 266, 270–273 delayed eruption of, 917 development of, 916–917, 1057

in Down syndrome, 306 grinding, 140–141 infections in, 274–275 infections of, 318, 319 primary, retention of, 466 trauma to, 276–277 Teething, 916–917 Telogen effluvium, 32–33 Temporomandibular joint (TMJ) disorders, 140, 141, 318, 319 Tendinosis, 918–919 Tendonitis, 918–919 Tendon transfer, for brachial plexus palsy, 117 Tenesmus, 298 Tensilon test, 617 Tension headache, 416 Tension pneumothorax, 719, 781 Teratoid tumor, 122 Teratoma, 2, 384–385, 432 Terminal ileus, 1022 Testes ambiguous genitalia and, 38–39 atrophic, 246 retractile, 246, 247 undescended (See Cryptorchidism) vanishing, 246 Testicular atrophy, 246, 991 Testicular cancer, 247, 384 Testicular germ cell tumors, 384–385 Testicular hypotrophy, 990, 991 Testicular ischemia, 515 Testicular masses, 794 Testicular regression syndrome, 1052 Testicular rupture, 921 Testicular seminomas, 384 Testicular torsion, 2, 242, 243, 458, 920–921 Tetanus, 46, 47, 922–923 Tetanus immune globulin (TIG), 922, 923 Tetanus prophylaxis, 375, 922 Tetanus vaccine, 73, 572, 573, 843 Tetany, 418, 419, 474, 475, 801 Tethered cord, 506, 638, 820, 928

Tetralogy of Fallot, 266, 306, 924–925, 994, 1041 “Tet spell,” 924–925 Thalassemias, 926–927 hemolysis in, 424, 425, 926 pallor in, 670 splenic function in, 72 Thanatophoric dysplasia, 1052 Thelarche, premature, 738–739 Theophylline poisoning, 902, 903 Therapeutic hypothermia, 634, 635 Therapy-related myelodysplastic syndrome (t-MDS), 147 Thermal injury, 374 Third disease, 386–387. See also Rubella Thirst, in diabetes insipidus, 286 Thoracic insufficiency syndrome, 928–929 Thrombocytopenia, 8–9 acquired, 8 in acute lymphoblastic leukemia, 22 in acute myeloid leukemia, 24 bruising in, 138–139 congenital amegakaryocytic, 1045 in hemolytic uremic syndrome, 428–429 in immune thrombocytopenic purpura, 500–501 marrow infiltration, 8 with mediastinal mass, 582 in meningococcemia, 589 in necrotizing enterocolitis, 624, 625 neonatal alloimmune, 628–629 petechiae in, 358 sequestration, 8 in 22q11.2 deletion syndrome, 266 in Wiskott-Aldrich syndrome, 1020–1021 Thrombocytopenia absent radius (TAR), 138, 1052 Thrombocytopenic purpura fever and petechiae in, 138, 139 immune, 138, 139, 358, 500–501 roseola and, 807 thrombotic, 396, 397, 424, 425, 428 Thromboembolic pulmonary embolism, 756 Thrombolytic therapy, 757, 931 Thrombophlebitis, 126, 164

Thrombosis, 930–931. See also specific disorders in cancer therapy, 146 in inflammatory bowel disease, 973 in Kawasaki disease, 536–537, 930 in nephrotic syndrome, 637 Thrombotic microangiopathy, 113 Thrombotic thrombocytopenic purpura (TTP), 396, 397, 424, 425, 428 Thrush, 128, 148, 149, 294, 499, 840 “Thunderclap” headache, 522 Thymectomy, 617 Thymic cyst, 622 Thymoma, 424 Thymus transplantation, 499 Thyroglossal duct cyst, 622 Thyroid cancer, 147, 398, 399 Thyroid dysfunction. See also Hyperthyroidism; Hypothyroidism cancer therapy and, 146 Thyroidectomy, 399, 405 Thyroiditis, 398, 399, 404 autoimmune, 162, 492, 970 chronic lymphocytic, 492, 493 earache in, 319 Hashimoto, 288, 299, 398, 492, 623 in mumps, 611 neck masses with, 623 in type 1 diabetes mellitus, 288 Thyroid storm, 404 Thyromegaly, 398, 742 Thyrotoxicosis, 464, 623 Tibial/femoral torsion, 520–521 Tibial torsion, 200 Tic(s), 934–935 Tic disorder, 86, 89, 414, 888, 934–935 Tick-borne illnesses. See also specific illnesses ehrlichiosis and anaplasmosis, 324–325 encephalitis, 1012 Lyme disease, 558–559 rickettsial, 802–803 Rocky Mountain spotted fever, 804–805 tularemia, 969 Tick-borne relapsing fever (TBRF), 932–933

Tick fever, 932–933 Tick paralysis, 616 Tietze syndrome, 234 Tinea capitis, 32–33, 378–379 Tinea corporis, 378–379 Tinea versicolor, 378–379 Tinnitus, 318, 319 Tobacco use, 892, 893 Toddler’s diarrhea, 376–377 Tolosa-Hunt syndrome, 158 Tongue in ankyloglossia, 52–53, 128, 129, 867 in glossitis, 353, 526, 584, 602, 670, 914 Tonsillar diphtheria, 300, 301 Tonsillectomy, 505, 695, 703 Tonsillitis earache with, 318 peritonsillar abscess with, 694–695 sore throat with, 862 streptococcal pharyngitis and, 702 tularemia and, 969 Tonsillopharyngitis, 340 TORCH syndrome, 436, 532, 632, 633 Torsades de pointes, 553, 996, 997 Torticollis, 520, 622, 694, 788, 882 Total parenteral nutrition (TPN) cholelithiasis in, 184, 185 cholestasis in, 632 hepatomegaly with, 436, 437 Tourette syndrome (TS), 414, 654, 888, 934–935 Townes-Brocks syndrome, 194, 506, 1052 Toxic alcohols, 936–937 Toxic epidermal necrolysis (TEN), 342, 343, 874, 878–879 Toxic megacolon, 2, 3, 239, 973 Toxic methemoglobinemia, 600–601 Toxic shock syndrome (TSS), 938–939 staphylococcal, 938–939 streptococcal, 819, 884, 885, 938–939, 943 Toxocara canis, 66 Toxoplasma gondii, 940 Toxoplasmosis, 370–371, 940–941

developmental delay with, 282 fever of unknown origin in, 360, 361, 940 in HIV, 455, 941 hydrocephalus in, 460, 940, 941 intellectual disability with, 516, 941 neck masses in, 622 Tracheal compression, 583 Tracheitis, 240, 338, 942–943 Tracheobronchomalacia, 137 Tracheoesophageal fistula (TEF), 306, 506, 944–945, 1014 Tracheomalacia, 236, 306, 945, 946–947, 1014, 1015 Tracheostomy, hemoptysis with, 432, 433 Trachoma, 180 Traction alopecia, 32 Tanscutaneous electrical nerve stimulation (TENS) for bladder dysfunction, 107 for dysmenorrhea, 313 Transdermal contraceptives, 228, 313 Transfusion-associated circulatory overload (TACO), 948–949 Transfusion-associated graft-versus-host disease (TA-GVHD), 948–949 Transfusion reaction, 304, 948–949 Transfusion-related acute lung injury (TRALI), 948–949 Transgender youth, 950–951 Transient erythroblastopenia of childhood, 952–953 Transient hypogammaglobulinemia of infancy, 476, 498 Transient myeloproliferative disorder, 25, 468, 548 Transient neonatal myasthenia, 616–617 Transient synovitis, 908–909 Transient tachypnea of newborn, 584, 954–955 Transjugular intrahepatic portosystemic shunting (TIPS), 69, 197, 731 Transmissible mink encephalopathy, 744 Transmissible spongiform encephalopathies, 744–745 Transplant patients. See also specific types of transplants candidiasis in, 148 graft-versus-host disease in, 402–403 lymphoproliferative disorders in, 564–565 sepsis in, 830 Transposition of great arteries, 956–957, 1041 Transsphenoidal surgery (TSS), 251 Transverse myelitis (TM), 157, 958–959 Trauma. See also specific injuries and conditions

in child abuse, 178–179 dental, 276–277, 319 disseminated intravascular coagulation in, 304 Traumatic brain injury (TBI), 120–121, 214–215 Traveler’s diarrhea, 144–145 Treacher Collins syndrome, 232, 852, 1052 Trendelenburg gait, 92 Treponema pallidum, 126, 910–911. See also Syphilis Trevor disease, 92 Triad syndrome, 462, 463, 976 Triangular alopecia, 32 Trichinella, 960. See also Trichinosis Trichinosis, 360, 370–371, 960–961 Trichobezoar, 102–103, 962, 963 Trichodystrophies, 32 Trichomoniasis, 681, 1062 cervicitis in, 168–169 sexual abuse and, 842–843 vaginitis in, 988, 989 Trichophagia, 102, 962, 963 Trichorhinophalangeal, 1052 Trichotillomania (TTM), 32–33, 102, 654, 962–963 Trichuris trichiura, 66 Trigeminal autonomic cephalgias, 416 Triglycerides, elevated levels of, 470–471, 598–599. See also Hyperlipidemia Trigonella foenum-graecum, 129 Triploidy, 1052 Triptans, 5, 255, 417 Trismus, 922 Trisomy 13, 154, 296, 392, 460, 944, 1052 Trisomy 15, 154 Trisomy 18, 154, 296, 460, 944, 1052 Trisomy 21. See Down syndrome Trousseau sign, 474 Truncus arteriosus, 220, 266, 994 Tuberculosis, 964–965 ascites in, 68 cavernous sinus syndrome in, 158 dysuria in, 316 erythema nodosum in, 344, 345 fever of unknown origin in, 360, 361

gastritis in, 380 hemoptysis in, 432, 433 hepatomegaly in, 436, 964 hypercalcemia in, 464 leukocytosis in, 548 neck masses with, 622, 623 perirectal abscess in, 690, 691 Tuberculous meningitis, 586–587, 964, 965 Tuberous sclerosis complex (TSC), 966–967 brain tumors in, 122, 966 developmental delay in, 282 infantile spasms in, 510, 511, 966, 967 intellectual disability in, 516, 966 renal artery stenosis in, 774 Tuboovarian abscess, 169, 680 Tubular necrosis, acute, 18 Tubular proteinuria, 746 Tufted angioma, 420 Tularemia, 360, 361, 968–969 Tumor(s). See also Cancer; specific types abdominal, 2–3 brain, 122–123 germ cell, 2–3, 122–123, 306, 384–385 Tumor lysis syndrome with acute lymphoblastic leukemia, 23 with acute myeloid leukemia, 24, 25 with hyperleukocytosis, 468–469 with non-Hodgkin lymphoma, 647 Tumor necrosis factor receptor–associated periodic fever syndrome (TRAPS), 360 Turcot syndrome, 122, 728 Turmeric, 531 Turner syndrome, 970–971 ambiguous genitalia in, 38 amenorrhea in, 44 cataract in, 154 celiac disease with, 162, 970 delayed puberty in, 754 germ cell tumors in, 384 growth hormone deficiency in, 406 lymphedema in, 562 short stature in, 844, 845, 970, 971

thyroid dysfunction in, 404, 492, 970 12-step programs, 893 22q11.2 deletion syndrome, 266–267, 1044 cleft lip/palate in, 198 esophageal atresia/TEF in, 944 hypocalcemia in, 266–267, 474 immune deficiency in, 266–267, 498, 499 neural tube defects in, 638 short stature in, 845 ventricular septal defect in, 994 22 tetrasomy syndrome (cat eye syndrome), 1045 Tympanic membrane rupture, 318, 669 Tympanostomy tube, 319, 669 Typhoidal tularemia, 968 Typhoid fever, 360, 812–813 Typhoid vaccine, 812 Typhus, 802–803 Tyrosinemia, 532, 592–593, 633, 730, 776, 1052 U Ulcer(s) aphthous, 319, 388, 412, 880 genital, 170–171, 340 in hand, foot, and mouth disease, 412–413 leg, in hereditary spherocytosis, 441 oral, in Crohn disease, 238 peptic, 380–381, 974–975 pressure, 959 rectal, 771 vaginal, 316 Ulcerative colitis, 770, 972–973 Ulcerative jejunoileitis, 163 Ulceroglandular tularemia, 968, 969 Ulipristal acetate (UPA), 228, 231 Ullrich muscular dystrophy, 614 Ultraviolet light, for hepatitis-related pruritus, 193 Umbilical cord blood transplantation (UCBT), 112 Umbilical cord clamping, delayed, 427 Umbilical hernia, 2 Umbilical stump infection (omphalitis), 160, 656–657, 692, 832 Uncinaria stenocephala, 252 Unconjugated hyperbilirubinemia, 532–533, 534

Underactive bladder, 106, 262 Undernutrition, 570–571 Undescended testes. See Cryptorchidism Undifferentiated arthritis, 64 Unexplained event, brief resolved, 132–133, 178, 686 Ungual fibromas, 966 Upper airway resistance syndrome, 852 Upper gastrointestinal bleeding (UGIB), 974–975 Upper respiratory infection (URI), 236–237, 240, 318, 850–851 Urachal cyst, 2 Urea cycle defects, 363, 592–595, 597, 633 Uremic pericarditis, 685 Ureter, ectopic, 462, 463, 998 Ureteral duplication, 998 Ureterocele, 462, 463, 608 Ureteropelvic junction obstruction, 2, 462, 463, 608, 976–977 Ureterovesical junction obstruction, 462, 463 Urethral atresia, 462 Urethral stricture, 316 Urethral valves, posterior, 262, 462, 463, 732–733 Urethritis dysuria in, 316, 317 gonococcal, 400 hematuria in, 422 Kawasaki disease and, 536 pinworms and, 708 Urinary bladder. See Bladder Urinary incontinence, 106–107, 332–333 cancer therapy and, 146, 147 daytime, 106, 262–263, 332 encopresis with, 328, 332 enuresis, 106, 262, 328 in exstrophy-epispadias complex, 350–351 giggle, 262 in Hirschsprung disease, 447 imperforate anus and, 507 nocturnal, 106, 262, 328, 332–333 in pertussis, 701 posterior urethral valves and, 732, 733 stress, 332 Urinary tract dilation (UTD), 462

Urinary tract infections (UTIs), 978–979 with candidiasis, 148, 149 with congenital hepatic fibrosis, 218 crying in, 243 dysuria in, 316–317 encopresis with, 328, 329 febrile, 762 fever of unknown origin in, 360, 361 with Hirschsprung disease, 447 hypertension in, 472 incontinence in, 106, 107, 262, 263, 332 lower, 978 (See also Cystitis) with neonatal sepsis, 832 with neural tube defects, 639 with posterior urethral valves, 732, 733 with RSV infections, 783 with transverse myelitis, 959 upper, 762–763 (See also Pyelonephritis) with ureteropelvic junction obstruction, 976, 977 urolithiasis in, 980 with vesicoureteral reflux, 978, 979, 998 Urination, painful. See Dysuria Urolithiasis, 316, 462, 980–981 Urotherapy, 333 Urticaria, 30, 982–983 in allergic rhinitis, 798 cellulitis vs., 164 in food allergy, 366 in giardiasis, 388, 389 papular, 748 solar, 706, 707 in transfusion reaction, 948–949 Urticaria pigmentosa, 982 Usher syndrome, 1052 Uterine bleeding, dysfunctional (abnormal), 310–311 Uterine duplication, 506 Uterine mass, 2–3 UTIs. See Urinary tract infections Uveitis, 222 with cataracts, 154 with Crohn disease, 238

with Ebola virus, 321 fever of unknown origin in, 361 with glaucoma, 392 with sarcoidosis, 814 with spondyloarthropathy, 873 with syphilis, 910 V Vaccine(s) adenovirus, 26 anthrax, 58 in asplenia, 73 BCG, 964 cholera, 186 diphtheria, tetanus, and pertussis, 300, 301, 700, 843, 922, 984–985 Ebola virus, 320 group A β-hemolytic Streptococcus, 884 Haemophilus influenzae type b, 73, 338, 358, 586, 662, 688, 830 for hemophilia patients, 431 hepatitis A, 1001 hepatitis B, 572, 573, 843, 1001 for HIV patients, 455 human papillomavirus, 456, 457, 843, 1008 in immune deficient patients, 499, 984 influenza, 358, 512, 513, 848, 985 measles, mumps rubella, and varicella, 610 and rubella, 326, 386, 576, 577, 610, 611, 984–985 meningococcal, 73, 358, 586, 588, 589, 830, 848 for NICU graduates, 364 pneumococcal, 73, 358, 549, 574, 688, 830, 848 rabies, 767 recommendations, 358 rotavirus, 808, 809, 985 rubella, 386 in sickle cell disease, 848 smallpox, 856, 857 in spinal muscular atrophy, 869 tetanus, 73, 375, 572, 573 22q11.2 deletion syndrome and, 266 typhoid, 812 varicella, 174, 984–985

Vaccine adverse events, 826, 837, 984–985 Vaccine refusal, 986–987 Vaccinia immune globulin (VIG), 857 VACTERL association, 194, 460, 506, 928, 944, 1052 Vaginal atresia, 506 Vaginal candidiasis, 148, 149, 288, 316, 988, 989, 1062 Vaginal reflux, 262, 263, 332 Vaginal ring, 228, 313 Vaginal ulcers, 316 Vaginitis, 316, 317, 400, 988–989, 1062 Vaginosis, 168, 681, 988, 989, 1062 Valerian, 313 Valproate fetal syndrome, 1046 Valsalva maneuver, for barotitis, 98, 99 Valve-bladder syndrome, 733 van der Woude syndrome, 198, 1052 Vanishing bile duct syndrome, 196 Vanishing testes syndrome, 246, 1052 Variant Creutzfeldt-Jakob disease, 744–745 Variceal hemorrhage, 974–975 in chronic hepatitis, 192 in cirrhosis, 68, 196, 197 in portal hypertension, 730–731 in portal vein obstruction, 160–161 Varicella, 174–175, 223, 316, 318, 326, 880, 1000, 1020 Varicella vaccine, 174, 984–985 Varicella zoster immunoglobulin, 174 Varicocele, 458, 778, 990–991 Variola virus (smallpox), 856–857 Vascular lesions, 420–421 congenital brain, 992–993 Vascular resistance, 994, 995, 1042 Vasoconstrictors, for nosebleeds, 650 Vasodilators for cor pulmonale, 233 for glomerulonephritis, 395 for hemolytic uremic syndrome, 429 for metabolic syndrome, 599 for pulmonary hypertension, 759 for renal artery stenosis, 775 Vaso-occlusive crisis, 848, 849

Vasopressin. See Antidiuretic hormone Vasovagal syncope, 904, 905 VATER association, 976 Vegetative state, persistent, 208 Vein of Galen malformations (VOGMs), 992–993 Velocardiofacial syndrome. See 22q11.2 deletion syndrome Venezuelan equine encephalitis, 1012 Venous malformations, 420–421 Venous sinus thrombophlebitis, 575 Ventilation in apnea, 631 in bronchopulmonary dysplasia, 137 in congenital diaphragmatic hernia, 296 for hypoplastic left heart syndrome, 488 in meconium aspiration syndrome, 581 in mediastinal mass, 582 in persistent pulmonary hypertension of newborn, 697 in pneumonia, 717 in pulmonary hypertension, 759 in respiratory distress syndrome, 780–781 in respiratory syncytial virus, 783 in severe acute respiratory syndrome, 839 in spinal muscular atrophy, 869 in tracheitis, 943 in transient tachypnea of newborn, 955 Ventral hernia, 2 Ventricular assist devices, 153, 221, 619 Ventricular septal defect (VSD), 220, 306, 924–925, 956–957, 994–995 Ventricular tachycardia, 996–997 Ventriculoperitoneal shunt, 461, 639, 876, 993 Ventriculosubgaleal shunt, 461 Verbal auditory agnosia, 864 Verbal dyspraxia, 864 Verrucae. See Warts Vertical expandable prosthetic titanium rib (VEPTR), 929 Vertical talus, 200 Vertigo, 318, 319, 416 Vesicoureteral reflux (VUR), 998–999 with cancer therapy, 147 with daytime incontinence, 262, 263 with exstrophy-epispadias complex, 350, 351

with hydronephrosis, 462, 463, 998 with imperforate anus, 506 with multicystic dysplastic kidney, 608 with neural tube defects, 639 with posterior urethral valves, 732, 733 with pyelonephritis, 762, 763 transverse myelitis and, 959 with ureteropelvic junction obstruction, 976 urinary tract infection with, 978, 979, 998 Vesicoureteral reflux and unilateral renal dysplasia (VURD) syndrome, 733 Vesicovaginal fistula, 316 Vesiculoulcerative stomatitis, 412–413 Vessel wall disorders, 9 Vestibular migraine, 78 Vestibular neuronitis, 78 Vibratory urticaria, 982 Vibrio cholerae, 186. See also Cholera Vibrio parahaemolyticus, 370, 1063 Viral encephalitis, 326 Viral hepatitis, 20–21, 192, 1000–1001 Viral meningitis, 586–587 Vision in amblyopia, 40–41 in cancer therapy, 147 in cataract, 154–155 in conjunctivitis, 222, 223 in Down syndrome, 306, 307 in fragile X syndrome, 372, 373 in glaucoma, 392–393 in hyperammonemia, 595 intracranial hypertension and, 496–497 in NICU graduates, 364 in orbital cellulitis, 164 in refractive error, 372, 374, 772–773, 1056 in retinoblastoma, 784–785 in retinopathy of prematurity, 786–787 in strabismus, 882–883 in toxoplasmosis, 940, 941 Vitamin(s) for chronic hepatitis, 193 for cirrhosis, 197

for congenital hepatic fibrosis, 219 for short-bowel syndrome, 846 Vitamin A for bronchopulmonary dysplasia, 136 for cholera, 187 for chronic hepatitis, 193 for cirrhosis, 197 for congenital hepatic fibrosis, 219 for measles, 577 Vitamin A deficiency, 496, 847 Vitamin A toxicity, 32, 242, 272, 436, 496, 730 Vitamin B12 deficiency, 584–585, 847 Vitamin B12 supplementation, 915 Vitamin C deficiency, 138 Vitamin D for 22q11.2 deletion syndrome, 266 in asthma, 76–77 for chronic hepatitis, 193 for chronic kidney disease, 195 for cirrhosis, 197 for congenital hepatic fibrosis, 219 for dermatomyositis/polymyositis, 281 for hypocalcemia, 474 for hypophosphatemic disorders, 485 infant supplementation, 129 for osteogenesis imperfecta, 661 for Perthes disease, 699 for renal tubular acidosis, 777 for rickets/osteomalacia, 801, 1065 for transverse myelitis, 959 Vitamin D deficiency back pain with, 96 hypocalcemia with, 484 hypophosphatemia with, 474, 475 in metabolic syndrome, 598 in obesity, 652 in renal tubular acidosis, 776, 777 in rickets, 800–801 in short-bowel syndrome, 847 in short stature, 844 Vitamin E

for ataxia, 79 for chronic hepatitis, 193 for cirrhosis, 197 for congenital hepatic fibrosis, 219 for Wilson disease, 1019 Vitamin E deficiency, 847 Vitamin K for chronic hepatitis, 193 for cirrhosis, 197 for congenital hepatic fibrosis, 219 for diabetic ketoacidosis, 293 for liver failure, 11, 21 for portal hypertension, 731 for Rocky Mountain spotted fever, 805 Vitamin K deficiency, 138, 139, 437, 847 Vitiligo, 492, 706, 707, 742 Voice disorders, 866 Voiding dysfunction, 106, 262, 316, 447 Volvulus, 1002–1003 abdominal mass with, 2, 3 intestinal obstruction with, 518, 519 lower GI bleeding with, 554 Meckel diverticulum and, 578 short-bowel syndrome with, 846, 1003 sigmoid, 225 Vomiting, 1004–1005. See also specific conditions causing in bulimia, 142–143, 1004 in cyclic vomiting syndrome, 254–255, 1004 dehydration in, 264–265, 1005 in food poisoning, 370–371 in gastroesophageal reflux disease, 382–383 hyponatremia in, 482 in pyloric stenosis, 764–765, 1004 weight loss in, 1011 von Gierke disease, 1052 von Hippel-Lindau disease, 122, 1052 von Willebrand disease, 430, 1006–1007 abnormal bleeding with, 8, 9, 1006 bruising with, 138, 139, 1006 Vulvovaginitis, 148, 149, 333, 708, 988, 989, 1062 VUR. See Vesicoureteral reflux

W Waardenburg syndrome, 446, 638, 1052 WAGR syndrome, 772, 1016, 1052 Walker-Warburg syndrome, 392, 460, 1052 Walled-off necrosis (WON), 672, 673, 675 Warfarin fetal syndrome, 1046 Warts, 1008–1009 anogenital, 1008, 1009 cutaneous, 1008 genital, 456–457, 843, 1008 laryngeal, 1008 Wasp sting, 858 Water deprivation test, 286, 486 Waterhouse-Friderichsen syndrome, 742 Waveforms, in electrocardiography, 1039 Webbed penis, 682 Wegener granulomatosis, 1052 Weight faltering, 352–353. See also Failure to thrive Weight loss, 1010–1011. See also specific conditions causing Werdnig-Hoffmann disease, 115, 868 Werner syndrome, 1052 Western equine encephalitis, 1012 Westley Croup Score, 240–241 West Nile virus (WNV), 326, 1012–1013 West syndrome, 510 Wet cough, 236 Wheezing, 236–237, 1014–1015 in allergic child, 30 with anaphylaxis, 48 with ascariasis, 66, 67 with aspergillosis, 70 with asthma, 74, 75, 1014, 1015 with bronchiolitis, 134, 135 with cardiomyopathy, 152 with chest pain, 172 with chlamydia, 180 with Chlamydophila pneumoniae, 182 with congestive heart failure, 220 with cystic fibrosis, 258, 1014 with dyspnea, 314 with food allergy, 366

with hemoptysis, 432 with lymphadenopathy, 560, 561 with meconium aspiration, 580 with mediastinal mass, 582, 583 with Pneumocystis jiroveci infection, 714 with pneumonia, 716 precautions with steroids in, 583 with RSV infection, 782, 783 with sickle cell disease, 848 with substance use disorders, 892 with tracheomalacia, 946 with transient tachypnea of newborn, 955 Whipple triad, 478 White coat hypertension, 472 Whooping cough. See Pertussis Wide-complex tachycardia, 900, 996 Wilkie syndrome, 898 Williams syndrome, 162, 262, 464, 774, 1052–1053 Wilms tumor, 2–3, 422, 1016–1017 Wilson disease, 1018–1019 ataxia with, 78 cataract with, 154 cirrhosis with, 196, 197 hepatitis with, 192 hepatomegaly with, 436, 437, 1018 jaundice with, 532, 533, 1018 portal hypertension with, 730 renal tubular acidosis in, 776 Wintergreen oil, toxicity of, 810, 811 Wiskott-Aldrich syndrome (WAS), 22, 498, 499, 1020–1021 Withdrawal, acute drug. See Acute drug withdrawal Wolff-Parkinson-White (WPW) syndrome, 900, 901, 1053 Wolf-Hirschhorn syndrome, 678, 1044 Wolman disease, 192, 1048 Wound botulism, 114–115 X Xanthelasma, 470 Xanthomas, 470, 532 Xeroderma pigmentosum, 706, 1053 Xerostomia, 147, 913 X-linked agammaglobulinemia (XLA), 210, 476, 498–499

X-linked hypophosphatemic (XLH) rickets, 484 X-linked lymphoproliferative syndrome (XLP), 340, 498–499, 564–565 X-linked spinal and bulbar muscular atrophy, 868 Xylitol chewing gum, 273 Y Yellow fever, 320, 1012 Yellow nail, 562 Yersinia enterocolitica, 370–371, 1022–1023, 1063 Yersinia pestis, 710–711 Yolk sac tumors, 384–385 Yuzpe method, 228 Z Zataria, 313 Zellweger syndrome, 392, 1053 Zika virus, 326, 364, 1024–1025 Zinc for cholera, 187 for diarrhea, 299 for dysmenorrhea, 313 for Wilson disease, 1019 Zinc deficiency, 32, 847 Zollinger-Ellison syndrome, 380 Zoster sine herpete, 175