Year Book of Dermatology - 2019 Fungal Infections [1 ed.] 9789390281237, 9789352709724

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YEAR BOOK OF DERMATOLOGY – 2019

FUNGAL INFECTIONS

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YEAR BOOK OF DERMATOLOGY – 2019

FUNGAL INFECTIONS Editor

Jayakar Thomas MD DD MNAMS FRCP FRCPCH PhD DSc Professor and Head Department of Dermatology Sree Balaji Medical College and Hospital Chennai, Tamil Nadu, India

Co-Editor Parimalam Kumar MD DD MNAMS FRCP Professor and Head Department of Dermatology Government Stanley Medical College and Hospital Chennai, Tamil Nadu, India

Foreword S Nirmala

JAYPEE BROTHERS MEDICAL PUBLISHERS The Health Sciences Publisher New Delhi | London | Panama

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Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected]

Overseas Offices J.P. Medical Ltd 83 Victoria Street, London SW1H 0HW (UK) Phone: +44 20 3170 8910 Fax: +44 (0)20 3008 6180 Email: [email protected]

Jaypee-Highlights Medical Publishers Inc City of Knowledge, Bld. 235, 2nd Floor, Clayton Panama City, Panama Phone: +1 507-301-0496 Fax: +1 507-301-0499 Email: [email protected]

Jaypee Brothers Medical Publishers (P) Ltd Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 Email: [email protected] Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2019, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. The CD/DVD-ROM (if any) provided in the sealed envelope with this book is complimentary and free of cost. Not meant for sale. Inquiries for bulk sales may be solicited at: [email protected] Year Book of Dermatology – 2019 Fungal Infections / Jayakar Thomas, Parimalam Kumar First Edition:  2019 ISBN: 978-93-5270-972-4 Printed at

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Dedicated to The many dermatologists who provide care to their patients with dermatophytoses, to our committed teachers, and most of all to our beloved spouses for their care, love, affection and support without which this humble piece of work would not have been a reality.

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CONTRIBUTORS   Editor  Jayakar Thomas MD DD MNAMS FRCP FRCPCH PhD DSc Professor and Head Department of Dermatology Sree Balaji Medical College and Hospital Chennai, Tamil Nadu, India

  Co-Editor  Parimalam Kumar MD DD MNAMS FRCP Professor and Head Department of Dermatology Government Stanley Medical College and Hospital Chennai, Tamil Nadu, India

  Contributing Authors Sobimeena RM MD Assistant Professor Department of Dermatology Sree Balaji Medical College and Hospital Chennai, Tamil Nadu, India

Vignesh NR MD Senior Resident Department of Dermatology Sree Balaji Medical College and Hospital Chennai, Tamil Nadu, India

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FOREWORD

S Nirmala MD DD Professor Department of Dermatology Madras Medical College Chennai, Tamil Nadu, India

It is indeed a privilege and pleasure to pen these lines of foreword for the title “Year Book of Dermatology – 2019 Fungal Infections”, edited by Professor Jayakar Thomas and co-edited by Professor Parimalam Kumar. I say this because I know Professor Jayakar Thomas as a voracious reader, popular teacher, and a masterly orator and also a great descriptive writer, as much as Professor Parimalam Kumar. I have been reading their several works—original articles, chapters in books and also his other books. The practice of medicine requires the acquisition of knowledge and skills, and the learning of attitudes and behaviors, apart from the manner in which it is disseminated. Professor Jayakar Thomas has exemplified this in this title “Year Book of Dermatology – 2019 Fungal Infections”. Year Book of Dermatology – 2019 Fungal Infections, is a compilation of some of the recent literature pertaining to various aspects of dermatophytoses. The authors have skillfully written their analytical comments on the articles and the end of each one sees the key messages to the same. This makes an easy and interesting reading. Speaking volumes about the motivation driven by Professor Thomas is the effort put in by the young contributors. I congratulate the contributors Dr Sobimeena RM and Dr Vignesh NR for working in liaison with Professor Jayakar Thomas.

It is my opinion that this book needs to be placed in the hands of all dermatologists.

I convey to Professor Jayakar Thomas and the contributors all my best wishes to more and more similar work towards academic excellence.

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PREFACE Dermatophytoses are the most common communicable dermatologic diseases seen in practice. Little wonder that bundles of papers are being published on dermatophytoses frequently. In this title “Year Book of Dermatology – 2019 Fungal Infections”, we have put in our best efforts to pick on some articles from recent literature and compile our views and comments on the same. We thank the original authors for their contribution.

We do hope that this book serves as a useful study guide to all our colleagues. Jayakar Thomas Parimalam Kumar Sobimeena RM Vignesh NR

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CONTENTS Section 1: Epidemiological Studies

1. Antifungal Activity of Silver Nanoparticles on Fluconazole Resistant Dermatophytes Identified by (GACA)4 and Isolated from Primary School Children Suffering from Tinea Capitis in Ismailia – Egypt

1



2. Interdigital Tinea Pedis Resulting from Fusarium Species in Dakar, Senegal

2



3. Emergence of African Species of Dermatophytes in Tinea Capitis: A 17‐Year Experience in a Montreal Pediatric Hospital

3

4. Topical Tavaborole in the Treatment of Onychomycosis Complicated by Dermatophytoma: A Post-hoc Assessment of Phase II Subjects

4

5. In vitro Antifungal Susceptibility Profiles of 12 Antifungal Drugs against 55 Trichophyton schoenleinii Isolates from Tinea Capitis Favosa Patients in Iran, Turkey and China

5

6. Characterizing the Clinical Isolates of Dermatophytes in Hamadan City, Central West of Iran, Using PCR-RLFP Method

6

7. A Comparative Study of the Various Patterns of Oro-cutaneous Fungi and their Sensitivity to Anti-fungals between HIV Patients and Normal Healthy Individuals

8

8. Frequency of Fungal Species of Onychomycosis between Diabetic and Non-diabetic Patients

9





9. Examining the Accuracy of Visual Diagnosis of Tinea Pedis and Tinea Unguium in Aged Care Facilities

10

10. Incidence and Biodiversity of Yeasts, Dermatophytes and Non-dermatophytes in Superficial Skin Infections in Assiut, Egypt

11

11. A Phase 2, Controlled, Dose-Ranging Study of SB208, an Investigational Topical Nitric Oxide-releasing Drug, for the Treatment of Tinea Pedis

12

12. Treatment of Onychomycosis Using a 1064-nm Diode Laser with or without Topical Antifungal Therapy: A Single-Center, Retrospective Analysis in 56 Patients

13

13. Epidemiological Survey of Onychomycosis Pathogens in Japan by Real-time PCR

14

14. Onychomycosis due to Dermatophytes Species in Iran: Prevalence Rates, Causative Agents, Predisposing Factors and Diagnosis Based on Microscopic Morphometric Findings

15

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xiv Year Book of Dermatology – 2019 Fungal Infections 15. Tinea unguium Onychomycosis Caused by Dermatophytes: A Ten-year (2005–2014) Retrospective Study in a Tertiary Hospital in Singapore

16

16. Epidemiology of Trichophyton verrucosum Infection in Rennes University Hospital, France: A 12-year Retrospective Study

17

17. Is Antifungal Resistance a Cause for Treatment Failure in Dermatophytosis: A Study Focused on Tinea Corporis and Cruris from a Tertiary Centre?

18

18. The Association between Tinea Pedis and Feet-washing Behavior in Patients with Diabetes: A Cross-sectional Study

19

19. Severe Dermatophytosis in Solid Organ Transplant Recipients: A French Retrospective Series and Literature Review

20

20. A Randomized, Double-blind Trial of Amorolfine 0.25% Cream and Sertaconazole 2% Cream in Limited Dermatophytosis

21

21. Dermatophytosis Due to Trichophyton Violaceum at the Parasitology-mycology Laboratory of the Military Hospital of Meknes (About Twelve Cases)

22

22. Use of Over-the-counter Topical Medications in Dermatophytosis: A Cross-sectional, Single-center, Pilot Study from a Tertiary Care Hospital

23

23. Tinea Faciei in a Central Portuguese Hospital: A 9-year Survey

24

24. A Survey Among Dermatologists: Diagnostics of Superficial Fungal Infections – What is Used and What is Needed to Initiate Therapy and Assess Efficacy?

25

25. Frequency of Mixed Onychomycosis with Total Nail Dystrophy in Patients Attended in a Guatemalan Dermatology Center

26

26. In vitro Antidermatophytic Activity and Cytotoxicity of Extracts Derived from Medicinal Plants and Marine Algae

27

27. Magnitude and Associated Risk Factors of Superficial Skin Fungal Infection Among Primary School Children in Southern Tanzania

29

28. The Efficacy and Safety of Eberconazole Nitrate 1% and Mometasone Furoate 0.1% w/w Cream in Subjects with Inflamed Cutaneous Mycoses

30

29. Study of Prevalence of Dermatophytes Among Human Immunodeficiency Virus/AIDS Patients in Shadan Institute of Medical Sciences and Teaching Hospital and Research Centre, Hyderabad, Telangana, India

31

30. Epidemiological Characteristics of Tinea Pedis in Military

32

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Contents

xv

Section 2: Diagnostic Studies

1. Onychomycosis Infections: Do Polymerase Chain Reaction and Culture Reports Agree?

34

2. Morphological Effect of the New Antifungal Agent ME1111 on Hyphal Growth of Trichophyton Mentagrophytes, Determined by Scanning and Transmission Electron Microscopy

35

3. Development and Evaluation of Indirect Enzyme Linked Immunosorbent Assay for the Serological Diagnosis of Microsporum Canis Infection in Humans

36

4. Clinical Evaluation of β‐tubulin Real‐time PCR for Rapid Diagnosis of Dermatophytosis, a Comparison with Mycological Methods

37

5. Polymerase Chain Reaction-restriction Fragment Length Polymorphism as a Confirmatory Test for Onychomycosis

38

6. Comparison of Photoinactivation of T. rubrum by New Methylene Blue (NMB) and Indocyanine Green (EmunDo®)

39



7. A Simple but Yet Novel Stain in the Diagnosis of Onychomycosis

40



8. Clinical Evaluation of the DermaGenius® Nail Real-time PCR Assay for the Detection of Dermatophytes and Candida Albicans in Nails

41





Section 3: Management Studies

1. Copaiba Oil and Its Constituent Copalic Acid as Chemotherapeutic Agents against Dermatophytes

43



2. Inhibition of Dermatophytes by Photodynamic Treatment with Curcumin

44



3. Antifungal Efficacy of Amphotericin B against Dermatophytes and its Relevance in Recalcitrant Dermatophytoses: A Commentary

45

4. A Review of the Most Effective Medicinal Plants for Dermatophytosis in Traditional Medicine

47

5. Investigation of the Antifungal Potential of Linalool Against Clinical Isolates of Fluconazole Resistant Trichophyton rubrum

48

6. Fractional Carbon Dioxide Laser Assisted Delivery of Topical Tazarotene versus Topical Tioconazole in the Treatment of Onychomycosis

49

7. Discovery of Antifungal Compounds from Kampo Medicine Against Dermatophytes

50



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xvi Year Book of Dermatology – 2019 Fungal Infections

8. Biosynthesized Silver and Gold Nanoparticles are Potent Antimycotics Against Opportunistic Pathogenic Yeasts and Dermatophytes

51

9. Triintsin, a Human Pathogenic Fungus-derived Defensin with Broad-spectrum Antimicrobial Activity

52

10. Onychomycosis in Children: Safety and Efficacy of Antifungal Agents

53

11. Anti-candidal Activity of Selected Analgesic Drugs Used Alone and in Combination with Fluconazole, Itraconazole, Voriconazole, Posaconazole and Isavuconazole

54

12. Antifungal Resistance in Dermatology

55

13. Antibiofilm Treatment for Onychomycosis and Chronic Fungal Infections

57

14. Newer Topical Treatments in Skin and Nail Dermatophyte Infections

58

15. Flavonoids from Plinia cauliflora (Mart.) Kausel (Myrtaceae) with Antifungal Activity

59

16. Biofilms and beyond: Expanding Echinocandin Utility

60

17. Clinical Laser Treatment of Toenail Onychomycoses

62

18. Evaluation of Biofilm Formation Ability in Different Candida Strains and Anti-biofilm Effects of Fe3O4-NPs Compared with Fluconazole: An in vitro Study

63

19. Luliconazole, A New Antifungal Against Candida Species Isolated from Different Sources

64

20. In vitro Additive Effect on Griseofulvin and Terbinafine Combinations Against Multidrug-resistant Dermatophytes

65

21. Traditionally Practiced Medicinal Plant Extracts Inhibit the Ergosterol Biosynthesis of Clinically Isolated Dermatophytic Pathogens

66

22. A Novel Antibiotic-like Substance Isolation from Dermatophyte, Trichophyton rubrum

67

23. Caffeic Acid and Licochalcone a Interfere with the Glyoxylate Cycle of Trichophyton rubrum

68

24. Efficiency of Newly Prepared Thiazole Derivatives Against Some Cutaneous Fungi

69

25. Management of Dermatophytosis of Nail and Hair

70

26. Challenges and Opportunities in the Management of Onychomycosis

71

27. In vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates

72

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Contents

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28. Pediatric Onychomycosis: The Emerging Role of Topical Therapy

73

29. Tacrolimus, not Triamcinolone Acetonide, Interacts Synergistically with Itraconazole, Terbinafine, Bifonazole, and Amorolfine against Clinical Dermatophyte Isolates

74

30. Efficacy and Tolerability of Amorolfine 5% Nail Lacquer in Combination with Systemic Antifungal Agents for Onychomycosis: A Meta-analysis and Systematic Review

75

31. Promising Antifungal Activity of Croton tricolor Stem Essential Oil Against Candida yeasts 76 32. Diffuse Dermatophytosis Occurring on Dimethyl Fumarate Therapy

77

33. In vivo Antifungal Activity of Dipyrithione Against Trichophyton rubrum on Guinea Pig Dermatophytosis Models

78

34. Antifungal Therapeutic Failures in India: An Important Issue being Overlooked

79

35. Utilization of Lichen Metabolites as Natural Antifungal Drug against Dermatophytosis 81 36. Investigation of Ethyl Cellulose Microsponge Gel for Topical Delivery of Eberconazole Nitrate for Fungal Therapy

82

37. A Comparative Study of Efficacy and Safety of Eberconazole versus Terbinafine in Patients of Tinea Versicolor

83

38. Antifungal Drug Susceptibility Profile of Clinically Important Dermatophytes and Determination of Point Mutations in Terbinafine-resistant Isolates

84

39. The Role of Shoe and Sock Sanitization in the Management of Superficial Fungal Infections of the Feet

85

40. Eberconazole—Pharmacological and Clinical Review

86

41. Propolis for the Treatment of Onychomycosis

87

42. A Comparative Study of Quality of Life of Eberconazole versus Terbinafine in Patients of Tinea Versicolor

88

Section 4: Miscellaneous Studies

1. Tinea folliculorum Complicating Tinea of the Glabrous Skin: An Important yet Neglected Entity

90

2. Coexistence of Fungal Infections in Psoriatic Nails and their Correlation with Severity of Nail Psoriasis

91

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xviii Year Book of Dermatology – 2019 Fungal Infections 3. A Novel Dermatophyte Relative, Nannizzia perplicata sp. nov., Isolated from a Case of Tinea Corporis in the United Kingdom

92



4. PRP8 Intein in Dermatophytes: Evolution and Species Identification

93



5. In silico Characterization of Tandem Repeats in Trichophyton rubrum and Related Dermatophytes Provides New Insights into their Role in Pathogenesis

94

6. The Frequency, Antifungal Susceptibility and Enzymatic Profiles of Candida Species in Cases of Onychomycosis Infection

96





7. IL-17-mediated Immunity Controls Skin Infection and T Helper 1 Response during Experimental Microsporum Canis Dermatophytosis 97



8. In vitro Biofilms and Antifungal Susceptibility of Dermatophyte and Non‐dermatophyte Moulds Involved in Foot Mycosis

98

9. Microstructural Alterations in the Onychomycotic and Psoriatic Nail: Relevance in Drug Delivery

99



10. Majocchi’s Granuloma: Current Perspectives

100

11. Superficial Fungal Infection among Patients with Immune Bullous Diseases

101

12. Emerging Atypical and Unusual Presentations of Dermatophytosis in India

102

13. Onychomycosis Secondary to Onychomadesis: An Underdiagnosed Manifestation

103

14. Quantitative and Structural Analyses of the in vitro and ex vivo Biofilm-forming Ability of Dermatophytes

104

15. Clinicopathological Features and Course of Cutaneous Protothecosis

105

16. Pustular Tinea Manuum from Trichophyton Erinacei Infection 106 17. Tinea of Vellus Hair: A Diagnostic and Therapeutic Challenge

107

18. Relationship of Amino Acid Concentrations in Blood with Occurrence of Dermatophytosis 109 19. Assessment of the Subtilisin Genes in Trichophyton rubrum and Microsporum canis from Dermatophytosis

110

20. Tinea Corporis Caused by Trichophyton equinum in a Rider and Review of Literature

111

21. In vitro Models of Dermatophyte Infection to Investigate Epidermal Barrier Alterations

112

Index

113

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Section 1: Epidemiological Studies ARTICLE 1

Antifungal Activity of Silver Nanoparticles on Fluconazole Resistant Dermatophytes Identified by (GACA)4 and Isolated from Primary School Children Suffering from Tinea Capitis in Ismailia – Egypt Amin ME, Azab MM, Hanora AM, et al. Antifungal activity of silver nanoparticles on fluconazole resistant dermatophytes identified by (GACA)4 and isolated from primary school children suffering from Tinea capitis in Ismailia – Egypt.

Cell Mol Biol. 2017;63(11):63-7.

Abstract The treatment of fungal infections in the recent times have become challenging due to the problems like relapses and drug resistance. The available antifungal drugs have seen the emergence of resistant strains due to improper usage. This study was conducted to determine the antimycotic activity of silver nanoparticles in cases of tinea capitis who are resistant to fluconazole. The results showed that the silver particles can be used for the treatment of tinea capitis caused by Trichophyton violaceum but not for Microsporum canis or Microsporum gypseum.

COMMENT The treatment of dermatophytosis ranges from topical and systemic therapy depending upon the site and the extent of involvement. Tinea capitis usually affects children and systemic agents are the mainstay of treatment. The gold standard agent for the treatment of tinea capitis in children is griseofulvin. The other agents which can be used are terbinafine, itraconazole and fluconazole. This study was performed to determine the antimycotic effect of silver nanoparticles against fluconazole resistant species of dermatophytes. This study was conducted in cases of tinea capitis who did not respond to

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fluconazole. The study included 112 cases of which 70 samples showed culture positivity. The organisms isolated were Trichophyton violaceum, Microsporum gypseum and Microsporum canis. The susceptibility of silver nano­particles was tested with disk diffusion technique and other methods. The results showed that only Trichophyton violaceum was susceptible to silver nanoparticles whereas the other two species did not respond to it. The drawback of this study is that fluconazole is not usually preferred in the treatment of tinea capitis in the presence of other agents. The result showed that only one organism is

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susceptible to this drug and the others do not and hence this drug can be given only to those

cases which are caused by T.violaceum which can be determined only by culture.

Key Message €€ Silver nanoparticles effective in fluconazole resistant cases caused by Trichophyton violaceum.

ARTICLE 2

Interdigital Tinea Pedis Resulting from Fusarium Species in Dakar, Senegal Diongue K, Diallo MA, Ndiaye M, et al. Interdigital tinea pedis resulting from Fusarium species in Dakar, Senegal.

J Mycol Med. 2018;28(1):227-31.

Abstract Tinea pedis is a dermatophyte infection involving the soles of the foot. Interdigital type of tinea pedis is also encountered. This study was conducted to highlight the incidence of Fusarium as a cause of interdigital type of tinea pedis. Fusarium as the causative agent of tinea pedis is not common. This article shows that fusarium can be a causative agent and should be treated early before hematogenous dissemination occurs.

COMMENT Fungal infection of the interdigital web spaces are caused by dermatophytes and Candida yeasts. Rarely it can be caused by Fusarium species. In this study which was conducted in Dakar, it was observed that Candida was most common cause of interdigital fungal infection followed by Fusarium and trailed by dermatophytes. This was a retrospective study conducted to highlight the fact that Fusarium species should be considered while treating cases

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of interdigital tinea pedis. The study was performed with KOH examination and fungal culture. It was found that Fusarium was the causative agent in 45% of cases and was common in the age group belonging to fourth decade. Also, it was seen commonly in immunocompetent individuals. The early recognition of this entity is important because if untreated or improperly treated it may lead to the hematogenous dissemination of the fungus.

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Key Messages €€ Fusarium species can be considered as the differential in the interdigital fungal infections €€ Early recognition is required to prevent hematogenous dissemination.

ARTICLE 3

Emergence of African Species of Dermatophytes in Tinea Capitis: A 17‐Year Experience in a Montreal Pediatric Hospital Marcoux D, Dang J, Auguste H, et al. Emergence of African species of dermatophytes in tinea capitis: A 17-year experience in a Montreal pediatric hospital.

Pediatr Dermatol. 2018;35:323-8.

Abstract Tinea capitis is the dermatophyte infection of the scalp commonly seen in children. The etiological agents of tinea capitis differs in different parts of the world depending on the geographical conditions. This study was conducted in Canada in patients of tinea capitis. The infection was common in African migrants and infection in family members was also seen. Microsporum audouinii was the commonest isolate and it was resistant to terbinafine.

COMMENT Tinea capitis is common in children before puberty due to the absence of sebum secretion which acts as a natural fungistatic action. The causative agent of tinea capitis differs in parts of the world due to change in the geographical factors required by the fungus. This retrospective study was performed because it was found that the rise in dermatophytosis caused by African species was noted in countries

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receiving African migrants. This study was conducted in Canada and the retrospective data suggests that there was six  times the increase in dermatophytosis caused by African species. The incidence of tinea capitis was high among children of African immigrants. Boys were commonly affected and preschool children were more affected. Microsporum audouinii was the common organism isolated

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Year Book of Dermatology – 2019 Fungal Infections

and this agent is known to cause epidemics of tinea capitis. The isolate in this study was resistant to terbinafine. This study shows the

importance of the geographical factors and immigration in isolation of new species in a new territory.

Key Messages €€ Microsporum

audouinii was the common organism isolated and this agent is known to cause epidemics of tinea capitis. The isolate in this study was resistant to terbinafine €€ This study shows the importance of the geographical factors and immigration in isolation of new species in a new territory.

ARTICLE 4

Topical Tavaborole in the Treatment of Onychomycosis Complicated by Dermatophytoma: A Post-hoc Assessment of Phase II Subjects Aly R, Winter T, Hall S, et al. Topical tavaborole in the treatment of onychomycosis complicated by dermatophytoma: A Post-hoc assessment of phase II subjects.

J Drugs Dermatol. 2018;17(3):347-54.

Abstract Tavaborole is an antifungal medication approved by FDA in the treatment of onychomycosis in the year 2014. This study was conducted to determine the efficacy of topical tavaborole in the treatment of onychomycosis which is complicated by the formation of dermatophytoma. This randomized controlled trial is in the phase II and the results are from this phase. The results show that topical tavaborole is effective in the treatment of onychomycosis as well in cases of onychomycosis complicated by dermatophytoma formation.

COMMENT Onychomycosis is the fungal infection of the nail caused by dermatophytes as well as non-dermatophytes. The diagnosis of onychomycosis is made clinically though various conditions like nail psoriasis and

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other conditions may mimic the presentation. Adding to this difficulty is the formation of dermatophytoma, an entity which is not known to many. A dermatophytoma presents as linear white/yellowish discoloration of

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5

Section 1: Epidemiological Studies the nail plate due to the formation of biofilm by the dermatophytes which is composed of fungal filaments and spores attached together by an extracellular polysaccharide material leading to poor treatment response even after oral antifungal therapy. The ideal treatment for the treatment of onychomycosis with dermatophytoma is by surgical/chemical treatment. This study was conducted to determine the efficacy of topical tavaborole in the treatment of onychomycosis complicated by dermatophytoma formation.

This study is a randomized controlled trial, still in the phase II has published its results. The results show that 24% of the patients of onychomycosis treated by this drug had complete resolution of the condition by 6 months and follow-up for 1  year showed that 26% of the patients had complete resolution. The findings show that topical tavaborole is quite effective in the treatment of onychomycosis complicated by dermatophytoma, the treatment of which was considered to be surgical/chemical in the past.

Key Message €€ Topical

tavaborole is effective in cases of onychomycosis complicated by dermatophytoma formation.

ARTICLE 5

In vitro Antifungal Susceptibility Profiles of 12 Antifungal Drugs against 55 Trichophyton schoenleinii Isolates from Tinea Capitis Favosa Patients in Iran, Turkey and China Deng S, Ansari S, Ilkit M, et al. In vitro antifungal susceptibility profiles of 12 antifungal drugs against 55 Trichophyton schoenleinii isolates from Tinea capitis Favosa patients in Iran, Turkey, and China.

Antimicrob Agents Chemother. 2017;61(2):e01753-16.

Abstract Trichophyton schoenleinii, a dermatophyte causes superficial fungal infections of which it is the causative agent of inflammatory type of tinea capitis, favus. This study was conducted to evaluate the most susceptible antifungal agent against Trichophtyton schoenleinii. In this in vitro study, the samples of the fungus was obtained from the last 30 years from Iran to China. The results showed that ketoconazole and terbinafine were the most potent antifungal agents against T. schoenleinii.

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COMMENT The epidemiological and mycological study of dermatophytosis has to be performed because of its importance in the changing pattern of causative agents of dermatophytosis and the susceptibility to antifungal agents. Favus is the inflammatory type of tinea capitis which is rare and seen commonly in the Kashmir valley. This type of tinea capitis is caused by Trichophyton schoenleinii although other dermatophytes belonging to the zoophilic and geophilic types can cause the condition. Griseofulvin is considered to be the gold standard drug for the treatment of tinea capitis in children, but the susceptibility of agents to the drug has decreased and this may lead to the administration of larger doses and longer duration of treatment. Other drugs like terbinafine and itraconazole have shorter duration of treatment and have fungicidal effect even after stoppage of the drug. So this

study was conducted to determine the most potent antifungal agent for favus. Isolates from 55 tinea capitis patients belonging to Iran, China and Turkey were chosen and cultured and later tested for drug susceptibility. Various antifungal agents that were tested are griseofulvin, fluconazole, itraconazole, terbinafine, ketoconazole, miconazole and amphotericin B. The results showed that except for fluconazole and flucytosine all the other drugs had inhibitory effect on T. schoenleinii. The most potent drugs to act against this organism were terbinafine and ketoconazole. This study gives us knowledge regarding the choice of antifungal agents in favus (tinea capitis) which is the least researched entity. The study results show that this can be applied to all geographical regions. More studies are required to support this.

Key Messages €€ All drugs except fluconazole and flucytosine had inhibitory effect on T. schoenleinii €€ The most potent agents were terbinafine and ketoconazole.

ARTICLE 6

Characterizing the Clinical Isolates of Dermatophytes in Hamadan City, Central West of Iran, Using PCR-RLFP Method Farokhipor S, Ghiasian SA, Nazeri H, et al. Characterizing the clinical isolates of dermatophytes in Hamadan city, Central west of Iran, using PCR-RLFP method.

J Mycol Med. 2018;28(1):101-5.

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7

Abstract Dermatophyte infections are encountered all over the world most commonly in the tropical regions. The diagnosis is mainly clinical but in order to know the epidemiological features, one should perform cultures and subcultures to identify the species causing the infection. This study was performed to analyse the use of molecular techniques like polymerase chain reaction and restricted fragment length polymorphism for the epidemiology of dermatophytic infections.

COMMENT Fungal culture and subculture techniques are performed for the identification of the species in clinical or research purposes. But the disadvantage of the above techniques is that they are time consuming and the results are not accurate all the time. This study was performed to determine the epidemiology of the dermatophytes using molecular techniques like PCR and RFLP. The samples collected were examined by direct microscope and cultures and later the isolates were identified using PCR technique using the Mval enzyme. The results showed that most common type of infection noted was tinea pedis followed by others. Trichophyton

interdigitale was the common isolate followed by Trichophyton rubrum. The study showed that molecular techniques can be used in epidemiological studies for faster and accurate identification of the causative species of dermatophytes. The last decade has seen lot of new developments in the field of biotechnology and molecular sciences which has led to easier and faster diagnosis of many diseases. The disadvantage of the above techniques is that the facility is not available in all centres in developing nations and also the cost of the techniques is quite high which is not affordable for everyone in the developing nations.

Key Message €€ The

study showed that molecular techniques can be used in epidemiological studies for faster and accurate identification of the causative species of dermatophytes.

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Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 7

A Comparative Study of the Various Patterns of Oro-cutaneous Fungi and their Sensitivity to Anti-fungals between HIV Patients and Normal Healthy Individuals Vijendran P, Verma R, Hazra N, et al. A comparative study of the various patterns of oro-cutaneous fungi and their sensitivity to anti-fungals between HIV patients and normal healthy individuals.

Medical Journal Armed Forces India. 2018.

Abstract Human immunodeficiency virus infection can have cutaneous manifestations in the form of cutaneous infections like bacterial, fungal and viral as well as other malignancies like Kaposi sarcoma. This study was performed to determine the etiological agents, clinical spectrum and drug sensitivity among HIV population and comparing it with normal healthy individuals.

COMMENT The HIV virus causes depletion of the helper T cells thereby leading to decrease in host immunity and leads to development of opportunistic infection. Among these, cutaneous infections are the most common manifestation. Atypical presentations are commonly encountered in HIV individuals and resistance to therapy is commonly encountered. This study was conducted to find out the clinical spectrum, etiological agents of fungal infections caused in HIV patients and comparing them with normal healthy population.

Skin samples in the form of swabs and scales were collected from the inguinal, dorsum of tongue and toe web spaces and direct microscopy and culture was performed. The results showed that HIV patients are more commonly affected from fungal infections compared to normal population. It was also observed that HIV patients harbor fungi even without clinical manifestation. This should be kept in mind while treating patients with HIV.

Key Messages €€ HIV patients are more commonly affected from fungal infections compared to normal population €€ HIV patients harbor fungi even without clinical manifestation.

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ARTICLE 8

Frequency of Fungal Species of Onychomycosis between Diabetic and Non-diabetic Patients Sultana S, Jaigirdar QH, Islam MA, et al. Frequency of fungal species of onychomycosis between diabetic and nondiabetic patients.

Mymensingh Med J. 2018;27(4):752-6.

Abstract Onychomycosis is the fungal infection of the nails caused by either dermatophytes or yeasts or non dermatophytic organisms. Onychomycosis can be frequently in diabetic patients or sometimes in cases of immunosuppressed patients. The present study was performed to find out the differences in causative agents of onychomycosis between diabetics and nondiabetics. The result showed that dermatophytes was commonly isolated in diabetic patients whereas Candida species and other non-Candida albican species.

COMMENT This study was performed to isolate the common organisms causing onychomycosis in diabetic and nondiabetic population. The causative agents in normal individuals and diabetic individuals vary and the importance in treatment duration depending upon the organisms grown. This was a cross-sectional study conducted in Bangladesh and clinically diagnosed patients of onychomycosis were divided into diabetic and non-diabetic groups. Routine investigations like direct microscopy and culture was performed in all the samples. The results were later then compared between the two groups.

The results showed that T. rubrum and T. mentagrophytes were commonly seen in diabetic patients whereas in non-diabetic patients Candida albicans and other species of Candida was seen. This information is impor­tant because the management between the two categories differs. Terbinafine is usually not effective against yeasts but effective against dermatophytes. Also the duration of treatment can vary between the two groups. The drawback of this study is the small sample size and more studies with larger sample size is required to determine the accurate pattern of onychomycosis among diabetics.

Key Message €€ Onychomycosis caused by dermatophytes was commonly seen in diabetic patients whereas Candida

species and other non-Candida albican species were isolated in non-diabetic patients.

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10 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 9

Examining the Accuracy of Visual Diagnosis of Tinea Pedis and Tinea Unguium in Aged Care Facilities Goto T, Nakagami G, Takehara K, et al. Examining the accuracy of visual diagnosis of tinea pedis and tinea unguium in aged care facilities.

J Wound Care. 2017;26(4):179-83.

Abstract This study was conducted to determine the accuracy of the visual diagnosis to aid in detecting skin problems like onychomycosis and tinea pedis in elderly population which are residing in the nursing homes and long-term health care facilities. This is a cross-sectional study in which a dermatologist performs a clinical examination in the intertriginous area of the finger and foot, later based on suspicion direct microscopy with KOH and culture was performed. It was found that scaling was more commonly observed in cases of tinea infection and not in others. The study showed that tinea infections are seen in elderly individuals but correlation was not found between the results.

COMMENT Skin disorders are commonly found in elderly population and is frequently found in elderly people residing in old age homes and orphanages. This cross-sectional study was performed to determine the accuracy of visual diagnosis by a dermatologist to aid in detecting skin problems like onychomycosis and tinea pedis. The study was conducted by macroscopic examination of the skin lesions in the two intertriginous area and foot and nails for detecting tinea pedis and onychomycosis.

After examination, cases who are clinically suspicious of tinea infection were subjected to direct microscopic examination and culture for confirmation of the clinical diagnosis. The results showed that scaling was commonly observed in elderly patients having tinea pedis and onychomycosis. The accuracy of diagnosis with clinical examination alone is low and hence other investigations are required to improve the diagnosis rate. Also, the correlation between the two methods were not satisfactory.

Key Message €€ The

accuracy of diagnosis of tinea pedis and onychomycosis with clinical examination alone is low and hence other investigations are required to improve the diagnosis rate.

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11

ARTICLE 10

Incidence and Biodiversity of Yeasts, Dermatophytes and Non-dermatophytes in Superficial Skin Infections in Assiut, Egypt Moubasher AH, Abdel-Sater MA, Soliman Z. Incidence and biodiversity of yeasts, dermatophytes and nondermatophytes in superficial skin infections in Assiut, Egypt.

J Mycol Med. 2016;27:166-79.

Abstract This study was conducted to determine the incidence of yeasts, dermatophytes and nondermatophyte infections and to isolate the causative organism causing each. The results showed that yeasts were the common agents isolated and onychomycosis cases were commonly found followed by tinea capitis.

COMMENT This study is a prospective study in which patients presenting with dermatophytosis, onychomycosis were clinically examined and subjected to direct microscopic examination, fungal culture and identification. The samples were collected form hair, nail clippings and skin scrapings. The results showed that onychomycosis was the commonly seen followed by tinea capitis in this study culture was positive in 96 cases and KOH positivity was seen in 45 cases. Yeasts were grown majority in culture followed by non-dermatophyte organisms.

Dermatophytes were grown in approximately 16% of the cases and this was leaded by Aspergillus species. It can be concluded that yeasts were commonly isolated followed by nondermatophyte organisms. The study recommends direct microscopy and culture for mycological evaluation of the fungal specimens. This study shows that etiological agents of fungal infections vary across the globe and treating physicians must be aware of the same to aid in proper drug selection and treatment.

Key Messages €€ Yeasts were the common agents isolated and onychomycosis cases were commonly found followed

by tinea capitis in this study

€€ Dermatophytes were not commonly isolated in this study.

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12 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 11

A Phase 2, Controlled, Dose-Ranging Study of SB208, an Investigational Topical Nitric Oxide-releasing Drug, for the Treatment of Tinea Pedis Elewski BE, Kircik LH, Stasko N, et al. A Phase 2, Controlled, Dose-Ranging Study of SB208, an Investigational Topical Nitric Oxide-releasing Drug, for the Treatment of Tinea Pedis.

J Drugs Dermatol. 2018;17(8):888-93.

Abstract Tinea pedis is the dermatophytic infection of the feet, the treatment of which depends on the type and extent of involvement. This randomized controlled trial was conducted to evaluate the effectiveness of the new drug SB208, a topical nitric oxide-releasing drug for the treatment of tinea pedis. The results showed that the drug provided good mycological cure and can be considered as an alternative agent for the treatment of dermatophytosis, in particular tinea pedis.

COMMENT This randomized controlled trial was conducted to evaluate the safety and efficacy of the new drug SB208, a topical nitric oxide releasing drug for the treatment of tinea pedis. This drug is a new drug of berdazimer sodium and hydrogel which releases nitric oxide at the lesional area. The study was performed by comparing the effect of the active drug and vehicle alone in patients at day 14 and 42. The drug was administered once daily. The patients were selected after clinical examination and followed by fungal culture and cases

positive by fungal culture alone were included in this study. After 14 days culture was performed to assess the mycological cure. At day 14 more patients in group treated with SB208 had mycological cure than the vehicle group. At day 42, greater number of patients in SB208 group showed mycological cure compared to vehicle group. The drug was considered to be relatively safe and had no major side effects. This shows that the drug is effective and well tolerated in the treatment of tinea pedis.

Key Messages €€ SB208 is a novel topical nitric oxide-releasing agent for the treatment of tinea pedis €€ The drug was considered to be relatively safe and had no major side effects.

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13

ARTICLE 12

Treatment of Onychomycosis Using a 1064-nm Diode Laser with or without Topical Antifungal Therapy: A SingleCenter, Retrospective Analysis in 56 Patients Weber GC, Firouzi P, Baran AM, et al. Treatment of onychomycosis using a 1064-nm diode laser with or without topical antifungal therapy: A single-center, retrospective analysis in 56 patients.

Eur J Med Res. 2018;23(1):53.

Abstract The management of onychomycosis by the topical and systemic antifungal agents have shown limited success due to the site and also nonadherence of the patient to the treatment due to increased duration of treatment. This study was conducted to analyze the therapeutic efficacy if onychomycosis treatment using 1064 nm diode laser. The results showed that the 1064 nm diode laser can be a safer and effective alternative in the treatment of onychomycosis.

COMMENT This is a retrospective study performed to assess the efficacy of nonablative laser (diode laser) alone or in combination with topical antifungal agents. The patients were selected after proper clinical examination and after histopathological and microbiological proven cases. Patients were divided into two groups, one receiving only laser therapy and the other with combination of laser with topical antifungal agents. The treatment was performed fortnightly for first three sessions and later performed every 6 weeks once. At the end of treatment, fungal

culture was performed to assess the mycolo­gical cure. The results showed that improvement was observed after 4–5 treatment sessions when laser was used alone and improvement was observed earlier in three settings when combined with topical anti­fungals. No side effects were reported in this study. It can be concluded that diode laser in combination with topical antifungals can provide faster and better results when either of those used alone. Also the curative rate can be increased when the number of laser sessions are increased.

Key Message €€ Diode laser in combination with topical antifungals can provide faster and better results when either

of the treatments used alone.

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14 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 13

Epidemiological Survey of Onychomycosis Pathogens in Japan by Real-time PCR Shimoyama H, Satoh K, Makimura K, Sei Y. Epidemiological survey of onychomycosis pathogens in Japan by real-time PCR.

Med Mycol. 2018.

Abstract The epidemiological study for fungal disorders is quite difficult because the investigations like fungal culture has low detection rates and hence molecular techniques like PCR can be performed for faster results with high sensitivity. This study portrays the use of real time PCR in the epidemiological survey of onychomycosis in Japan. The results showed that real time PCR had higher positivity rates and Trichophyton rubrum was the commonest isolated pathogen.

COMMENT The use of molecular techniques like PCR has been extended in the diagnosis of fungal infections especially onychomycosis because of the high positivity rate and faster results. This epide­miological study in Japan was conducted to assess the onychomycosis pathogens using real time PCR technique. Fungal culture was used in previous epidemiological studies but the result was positive in less than 40% of the cases and hence in this study PCR technique was used to determine the results. The results showed that Trichophyton rubrum was the commonest isolate followed

by Trichophyton interdigitale. The positivity rate was around 97%. The real time PCR technique had the advantage of detecting and isolation of organisms in almost all the samples. The study shows that in epidemiological studies PCR can be employed along with fungal culture for better sensitivity and positive predictive value. The disadvantage of this technique is that it is not available in all centres and in developing countries. More studies comparing culture and PCR techniques are required to conclude the superiority of PCR techniques.

Key Message €€ Real

time PCR had higher positivity rates and Trichophyton rubrum was the commonest isolated pathogen.

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15

ARTICLE 14

Onychomycosis due to Dermatophytes Species in Iran: Prevalence Rates, Causative Agents, Predisposing Factors and Diagnosis Based on Microscopic Morphometric Findings Babayani M, Salari S, Hashemi SJ, et al. Onychomycosis due to dermatophytes species in Iran: Prevalence rates, causative agents, predisposing factors and diagnosis based on microscopic morphometric findings.

J Mycol Med. 2018;28(1):45-50.

Abstract The fungal infection of the nail is onychomycosis. Dermatophytes, non-dermatophytes and yeasts are the causative agents. The study found out the etiological agent, predisposing factors and prevalence rate of onychomycosis in Iran using microscopic and clinical descriptions. Trichophyton rubrum tops the list. DLSO is the only pattern observed.

COMMENT Onychomycosis is the infection of the nail plate caused by dermatophytes, non-dermato­ phytic moulds and yeasts. Non-dermatophytic moulds that cause onychomycosis are Aspergillus, Acremonium species, Fusarium species, Scytalidium dimidiatum and Scropulariopsis brevicaulis. The study throws light on the prevalence rate and predisposing factors of onychomy­ cosis in one region of Iran. Nearly 230 nail clippings were collected and subjected to KOH mount microscopy and cultured using Mycosel agar and Sabouraud dextrose agar. The diagnostic criteria framed were segmental hyphae and arthrospores in KOH and culture positive in at least three points.

Fifty is the mean age group with female prepon­derance. Homemakers are more prone. In spite of excessive sweating surpri­singly onychomycosis are seen less in sportsmen. The study has found all cases to be distal lateral subungual onychomycosis though worldwide all five patterns were distributed. First three risk factors for Iranian population are elderly, female and diabetes. Interestingly, study has measured the fungal mycelia diameter using Olysia Software.Trichophyton rubrum tops the list followed by T. mentagrophytes. The study highlights that age group and predisposing factors vary region to region. Hence, studies should be conducted to find out the risk factors in that particular area and avoided accordingly.

Key Messages €€ Elderly, females and diabetes are the main risk factors for onychomycosis in Iranian population €€ Trichophyton rubrum tops the list followed by T. mentagrophytes.

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16 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 15

Tinea unguium Onychomycosis Caused by Dermatophytes: A Ten-year (2005–2014) Retrospective Study in a Tertiary Hospital in Singapore Pang SM, Pang JYY, Fook-Chong S, Tan AL. Tinea unguium onychomycosis caused by dermatophytes: A ten-year (2005–2014) retrospective study in a tertiary hospital in Singapore.

Singapore Med J. 2018;59(10):524-7.

Abstract The dermatophytic nail infection is tinea unguium. The study retrospectively analyzed the Tinea unguium in a tertiary hospital in Singapore. Nail specimens were inoculated in Sabouraud dextrose agar and Mycosel agar. Trichophyton rubrum was found to be the common etiological agent.

COMMENT The fungal nail infection is onychomycosis, when caused by dermatophytes it is termed as tinea unguium. The study is a retrospective one that analyze a 10-year period of tinea unguium cases in a tertiary hospital in Singapore. Nail specimens were retrieved from the microbiology laboratory and subjected to culture analyze in Sabouraud dextrose agar and Mycosel agar and examined weekly once. Trichophyton species analyses were done for few subspecies. More onychomycosis were seen in elderly individuals since; they were more prone for nail trauma and less personal nail care. Ethnical differences were recorded in onychomycosis with Chinese topping the list followed by

Indian and Malay. Male preponderance was seen. The various dermatophytes isolated in order were T. rubrum, T. mentagrophytes, unidentified Trichophyton species, T. tonsurans, Epidermophyton  floccosum, T. verrucosum, T. soudanense and T. violaceum.  Thus study had found out that in immunocompromised individuals rare organisms like T. tonsurans, T. verrucosum, T. soudanense and T. violaceum can cause tinea unguium. As the retrospective study collected only nail specimens, the clinical pattern could not be ascertained. Other limitation of the study is not able to differentiate finger and toe nail infections. There were nearly fifty specimens in which species identification was not made.

Key Messages €€ Ethnical differences were recorded in onychomycosis in a tertiary hospital in Singapore with Chinese

topping the list followed by Indian and Malay

€€ Elderly individuals are more prone for tinea unguium.

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17

ARTICLE 16

Epidemiology of Trichophyton verrucosum Infection in Rennes University Hospital, France: A 12-year Retrospective Study Courtellemont L, Chevrier S, Degeilh B, et al. Epidemiology of Trichophyton verrucosum infection in Rennes University Hospital, France: A 12-year retrospective study.

Med Mycol. 2017;55(7):720-4.

Abstract Trichophyton verrucosum is a zoophilic fungus that causes dermatophyte in adults and tinea capitis in children. The source of infection is from cattle. Humidity causes more cattle infection thereby increased human infection. This is a retrospective study which analyzes the epidemiological characteristics of Trichophyton verrucosum.

COMMENT The study highlights the epidemiological pattern of Trichophyton verrucosum, a zoo­ philic fungus which causes tinea corporis in adults and tinea capitis in children. About 1.5% Tricho­phyton verrucosum  was identified in a 12-year period. This infective rate is little higher compared to study in United States and Italy. But it is comparable to study in Poland and European countries. The study used culture medium like SDA and brain heart infusion agar. Trichophyton verrucosum  infections has a male predominance, this is because of men engaged in occupational activity with cattle.

Indirect exposure from soil source is also noted, as spores can remain viable for even 4 years. Humidity increases the infection among cattle, thereby more human infections. Thus more rainfall in last 4 years increases the case load of Trichophyton verrucosum. The study throws light that zoophilic dermatophyte infection varies in different region of the World. Hence treating physician should be aware of the epidemiological characteristics of that region and treat accordingly in order to avoid misdiagnosis.

Key Messages €€ Trichophyton verrucosum, a zoophilic fungus from cattle causes tinea capitis in children €€ Physician should be aware of the epidemiological characteristics of the particular region in order to

avoid misdiagnosis.

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18 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 17

Is Antifungal Resistance a Cause for Treatment Failure in Dermatophytosis: A Study Focused on Tinea Corporis and Cruris from a Tertiary Centre? Sardana K, Kaur R, Arora P, et al. Is antifungal resistance a cause for treatment failure in dermatophytosis: A study focused on tinea corporis and cruris from a tertiary centre?

Indian Dermatol Online J. 2018;9(2):90-5.

Abstract The study analyzes the antifungal resistance pattern in recalcitrant dermatophytosis. Forty tinea corporis and cruris patient treated with Itraconazole or terbinafine for 4 weeks and got relapse within 1 month are included in the study. Minimum inhibitory concentration at 50% and 90% of antifungals was recorded. The study discusses the antifungal effects mainly on T.  rubrum and T. mentagrophytes.

COMMENT In the last decade anti fungal resistance has been labeled as a cause for recalcitrant dermatophytosis. The study analyzes the anti fungal resistance pattern in recalcitrant tinea corporis and tinea cruris. Recurrent, reinfection, persistent cases are termed as recalcitrant dermatophytosis. Forty tinea corporis and cruris patient treated with either Itraconazole or terbinafine for 4 weeks and got relapse within 1 month of therapy are included in the study. Topical steroids were used by all patients. Minimum inhibitory concentration of fluconazole was found to be very high thus showing more antifungal resistance. In case of T. rubrum, MIC90 the order of antifungals potency are voriconazole, terbinafine/ amphotericin B/ketoconazole, itraconazole >fluconazole. For T. mentagrophytes, the order of potency of antifungals were voriconazole/

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itraconazole >terbinafine >amphotericin B >fluconazole. The study found T. mentagrophytes is the most common etiological agent. Before labeling anti fungal resistance, antifungal susceptibility test should be done. Multiple factors that responsible for recalcitrant dermatophytosis are any preceding illness, virulence of the fungi and duration of antifungals. Th1/Th2 response is subverted by the use of steroids. The limitations of the study are it has included only tinea corporis and tinea cruris. Griseofulvin is not taken into account. Further studies are needed for other type of tinea infections. The study concludes stating that antifungal resistance are not that common and before labeling multiple host and agent factors should be considered.

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Section 1: Epidemiological Studies

19

Key Messages €€ Multiple factors that responsible for recalcitrant dermatophytosis are any preceding illness, virulence

of the fungi and duration of antifungals €€ Thus antifungal resistance are not common cause for treatment failure.

ARTICLE 18

The Association between Tinea Pedis and Feet-washing Behavior in Patients with Diabetes: A Cross-sectional Study Takehara K, Amemiya A, Mugita Y, et al. The Association between Tinea Pedis and Feet-Washing Behavior in Patients with Diabetes: A Cross-sectional Study.

Adv Skin Wound Care. 2017;30(11):510-16.

Abstract The study is a cross-sectional one to find the link between tinea pedis and feet washing behavior in diabetic patients. The feet washing techniques such as scrubbing in between toes are analyzed. Proper feet washing can prevent tinea pedis effectively.

COMMENT This cross-sectional study records the feet washing behavior in diabetic patients who has tinea pedis. A total of 30 diabetic patients are included in the study. Sixteen of them had tinea pedis which is confirmed by KOH microscopy. Feet washing behavior such as scrubbing between toes of these tinea pedis patients were recorded in video and analyzed. Patient’s demographic details, knowledge regarding diabetes, tinea pedis and foot washing tech­ niques are evaluated. Any difficulty regarding feet washing and

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purpose of feet washing are enquired. The number of times scrubbing between the toes is indirectly proportional to tinea pedis. Tinea pedis patient also had difficulty in reaching toes with their hands. Effective foot washing technique might include eight toe web spaces for minimum 35 times. If patient have difficulty in reaching with hands then some instruments are needed. Tinea pedis can be effectively prevented by proper education regarding feet washing techniques.

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20 Year Book of Dermatology – 2019 Fungal Infections Key Messages €€ Tinea pedis can be effectively prevented by proper education regarding feet washing techniques €€ Effective feet washing technique might include all eight toe web spaces for atleast 35 times.

ARTICLE 19

Severe Dermatophytosis in Solid Organ Transplant Recipients: A French Retrospective Series and Literature Review Rouzaud C, Chosidow O, Brocard A, et al. Severe dermatophytosis in solid organ transplant recipients: A French retrospective series and literature review.

Transpl Infect Dis. 2018;20(1).

Abstract This orginal article has analyzed the dermatophytic pattern in solid organ transplant patients. Severe dermatophytosis found to be a late complication in solid organ transplant patients. Extensive treatments are needed.

COMMENT Solid organ transplant patients are more prone for infection because of immuno suppression. The fungal infections recorded in solid organ transplant patients are extensive dermatophytosis, candidiasis, crypto­coccosis, invasive aspergillosis and phaeohypomycosis. This article has analyzed the dermatophytic pattern in solid organ transplant patients. Dermatophytosis in solid organ transplant patients is found to be severe, extensive and invasive. Apart from the usual presentation, nodules are commonly seen. The median time interval between the transplant and onset of dermatophytosis is about 16 months. Longer

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treatment duration was required. However prognosis is good. Though no particular treatment guidelines exist, terbinafine found to be effective with good efficacy and safety profile. Other drug that can be given is posaconazole. Topical treatment plays an important role along with oral therapy. Surgery can be opted for very few localized lesions. In three patients, immunosuppressive therapy was reduced. In solid organ transplant patients, early recognition of superficial dermatophytosis is must. Early treatment is warranted to prevent the extensive, severe and invasive

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Section 1: Epidemiological Studies dermatophytosis in solid organ transplant. Whenever presence of limb nodules in the background of superficial dermatophytosis

21

in solid organ transplant patients invasive dermatophytosis should be considered and treated appropriately with terbinafine.

Key Message €€ The limb nodules in the background of superficial dermatophytosis in solid organ transplant patients,

invasive dermatophytosis should be considered and treated appropriately with terbinafine.

ARTICLE 20

A Randomized, Double-blind Trial of Amorolfine 0.25% Cream and Sertaconazole 2% Cream in Limited Dermatophytosis Das A, Sil A, Sarkar TK, et al. A randomized, double-blind trial of amorolfine 0.25% cream and sertaconazole 2% cream in limited dermatophytosis.

Indian J Dermatol Venereol Leprol. 2018.

Abstract Dermatophytosis response to the conventional antifungals has been reduced. This study compares the safety profile and efficacy of the two newer topical antifungal cream namely amorolfine 0.25% cream and sertaconazole 2% cream for limited tinea corporis and cruris. Sertoconazole cream is found to be more effective and highly tolerable compared to amorolfine.

COMMENT Because of reduced response to conventional anti fungals, newer antifungals are often produced in the market. This study compares the safety profile and efficacy of two such newer topical antifungal cream namely amorolfine 0.25% cream and sertaconazole 2% cream for limited tinea corporis and cruris.

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The study was a double blinded and randomized conducted in a single centre. The study takes into account of 66 untreated and KOH positive limited tinea cruris and corporis adult patients. They were divided into two groups, first group received amorolfine 0.25% cream and second group received sertaconazole 2% cream for a period of

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22 Year Book of Dermatology – 2019 Fungal Infections 4  weeks applied twice daily. Follow-up was done every week. At each visit, clinical improvement, mycological cure and improvement of symptoms were assessed. Any emergency adverse reactions were looked for. Routine laboratory investigations were done. Both groups showed improvement in symptoms; however sertaconazole group showed a better symptom improvement such as reduced itching, burning, redness and scaling. The number of lesions also found to be reduced in sertaconazole group at each visit.

In total, dermatology quality life index was very much improved in sertaconazole group. Adverse effects are similar in both groups. Ninety two percent showed fungal culture negative in sertaconazole group compared to 80% in amorolfine group. The limitations of the study are anti­ fungal susceptibility testing was not done and less number of study population. The study concludes that sertaconazole group is superior in treating limited tinea corporis and cruris compared to amorolfine group.

Key Message €€ Sertaconazole cream is effective than amorolfine cream in limited tinea cruris and corporis.

ARTICLE 21

Dermatophytosis Due to Trichophyton Violaceum at the Parasitology-mycology Laboratory of the Military Hospital of Meknes (About Twelve Cases) Zoulati G, Maïga RY, El Haouri M, et al. Dermatophytosis due to Trichophyton violaceum at the parasitology-mycology laboratory of the military hospital of Meknes (about twelve cases).

J Mycol Med. 2018;28(1):1-7.

Abstract Trichophyton violaceum is an anthropophilic fungus often infecting the children mostly seen in African and Mediterranean countries. This study is descriptive retrospective study evaluating the epidemiological and clinical profile of Trichophyton violaceum.

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Section 1: Epidemiological Studies

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COMMENT Trichophyton violaceum is an anthro­ pophilic fungus. It often infects school going children and commonly seen in African and Mediterranean countries. This is descriptive retrospective study evaluating the epidemiological and clinical profile of Trichophyton violaceum. The mean age of presentation is around eight years. All forms of dermatophytosis are caused by Trichophyton violaceum. However most common presentation is tinea capitis followed by onychomycosis. It rarely causes

erythroderma. Trichophytic tinea was mainly seen among tinea capitis. The other presentation is pustulo inflammatory tinea. Potassium hydroxide microscopy was positive in all cases of Trichophyton violaceum infection. Endothrix organism is seen in all cases. In case of clinical dilemma mycological examination plays an important role in diagnosing the condition. Trichophyton violaceum is an infection of school going children with tinea capitis as a major presentation.

Key Message €€ Trichophyton violaceum is an anthropophilic infection of school going children with tinea capitis as

a key presentation.

ARTICLE 22

Use of Over-the-counter Topical Medications in Dermatophytosis: A Cross-sectional, Single-center, Pilot Study from a Tertiary Care Hospital Dabas R, Janney MS, Subramaniyan R, et al. Use of over-the-counter topical medications in dermatophytosis: A crosssectional, single-center, pilot study from a tertiary care hospital.

Indian J Drugs Dermatol. 2018;4:13-7.

Abstract The use of over-the-counter topical preparations for dermatophytosis are increasing in developing countries especially India. This study assesses the rising threat of over-the-counter topical preparations. Clobetasol based topical preparations are commonly abused for tinea cruris. Nearly 90% of the study population was totally unaware of the side effects of the high potent steroid they are using for a fungal infection.

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24 Year Book of Dermatology – 2019 Fungal Infections COMMENT Dermatophytosis is one of the common condition for which people seek over-thecounter topical preparations in India. However studies are lacking regarding this rising drug abuse. This is observational, cross-sectional, questionnaire based study in a tertiary care centre. This study assesses the rising threat of over-the-counter topical preparations. The study population is hundred mycolo­ gically proven dermatophytosis cases who were given a questionnaire regarding the use of over-the-counter topical preparations and their adverse effects. There were about 25 females and 75 males. The most common clinical presentation for which over-thecounter topical preparations seeked is tinea cruris, this would be because of patient feeling shy reporting to the doctor.

About 68% only has consulted dermato­ logist on getting a rash, rest 32% followed medictions suggested by other people. Clobetasol based topical preparations are commonly abused. The adverse effects were experienced by about 64%. Surprisingly about 90% of study population was totally unaware of the adverse effects of the potent topical steroid they were using for a common fungal infection. The study alarms on the rising threat of the over-the-counter topical preparations drug abuse for a common fungal infection in India. Steps should be taken to control the use of over-the-counter topical preparations. The need for the day is to create awareness among the public regarding the adverse effects of the over-the-counter topical preparations.

Key Messages €€ Steps should be taken to control the use of over-the-counter topical preparations €€ It is important to create awareness regarding the harmful side effects of potent steroids.

ARTICLE 23

Tinea Faciei in a Central Portuguese Hospital: A 9-year Survey Borges A, Brasileiro A, Galhardas C, Apetato M. Tinea faciei in a central Portuguese hospital: A 9-year survey.

Mycoses. 2018;61(4):283-5.

Abstract The dermatophytic infection of the glabrous skin of face is termed as tinea faciei. It is a rare dermatophytic presentation. The study analyzes the mycological, clinical and epidemiological features of tinea faciei in a Portuguese hospital. The common etiological agent was found to be anthropophilic dermatophytes.

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Section 1: Epidemiological Studies

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COMMENT Dermatophytic infection of the face is uncommon and termed as tinea faciei. The study retrospectively analyzes the mycological, clinical and epidemiological features of tinea faciei in a central Portuguese hospital. About 72 tinea faciei cases have been described. Out of which 37 were male and 35 were female. The age group was between 8 months and 80 years. Nearly 60% were in the paediatric age group. The etiological agents belong to anthropophilic group such as T. rubrum,

T.  soudanense, Microsporum audouinii in 75%. Other areas such as scalp were affected in 25%. About ten cases were treated with topical steroids because of misdiagnosis. Most patients respond well to topical and systemic antifungals with complete cure without relapse or noticeable side effects. The study has found out that anthropophilic agent causes tinea faciei contrast to the European nation. Thus epidemiology of the dermatophytes differs country to country and studies are needed for each zone for proper treatment.

Key Message €€ The

study has found out that anthropophilic agent causes tinea faciei which is contrast to the European nation.

ARTICLE 24

A Survey Among Dermatologists: Diagnostics of Superficial Fungal Infections – What is Used and What is Needed to Initiate Therapy and Assess Efficacy? Saunte DML, Piraccini BM, Sergeev AY, et al. A survey among dermatologists: Diagnostics of superficial fungal infections– what is used and what is needed to initiate therapy and assess efficacy?

J Eur Acad Dermatol Venereol. 2018.

Abstract Dermatophytosis is very common and dermatologists need to handle them each day. This study is a survey to assess the newer diagnostic modalities and treatment efficacy for dermatophytosis. The study focus on whether it is must to differentiate initial diagnostic modalities and those used for treatment follow-up.

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26 Year Book of Dermatology – 2019 Fungal Infections COMMENT Recalcitrant dermatophytosis is emerging problem and gives a tough task for treating dermatologists. It is essential to confirm the diagnosis by laboratory methods and does antifungal susceptibility test before starting the therapy. Potassium hydroxide microscopy is the gold standard test to diagnose a fungal infection. It is confirmed by fungal culture. Recently newer molecular based investigations are developed for identification of the fungal species. This study is a survey taken to the dermatologist to assess the newer diagnostic modalities and treatment efficacy for dermatophytosis. The study particularly focuses on whether it is must to differentiate initial diagnostic modalities and those used for treatment follow-up. The survey is conducted

to dermatologist by an online questionnaire method. About 62 dermatologists were included for the survey. Of which 61% completed the whole survey, eleven percent partially completed and 27% did not respond to the survey. All responders were using KOH microscopy as a first hand diagnostic tool. Most of them used combined clinical assessment and microscopy to assess the treatment. None of them had molecular based diagnostic tools. The study concluded that dermatologist use KOH microscopy for diagnosing and species identification before starting systemic antifungals. Molecular diagnostic methods are often not available because of cost factor. The limitation of the study are sample size is small and molecular diagnostic methods are not available to assess its efficacy.

Key Message €€ The study concluded that dermatologist use KOH microscopy for diagnosing and species identification

before starting systemic antifungals.

ARTICLE 25

Frequency of Mixed Onychomycosis with Total Nail Dystrophy in Patients Attended in a Guatemalan Dermatology Center Martínez-Herrera Erick, Schlager-Ospino Herbert, Torres-Guerrero Edoardo, et al. Frequency of mixed onychomycosis with total nail dystrophy in patients attended in a Guatemalan Dermatology Center.

Infectio. 2018;22(2):105-9.

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Section 1: Epidemiological Studies

27

Abstract Mixed onychomycosis are due to combined infection of two dermatophytes, yeast/dermato­ phytes or non dermatophytes/dermatophytes. The study evaluates the frequency of total nail dystrophy due to mixed onychomycosis. Diabetes found to have a strong association with mixed onychomycosis.

COMMENT Combined infection of two dermatophytes, yeast/dermatophytes or non-dermatophytes/ dermatophytes of the nail is termed as mixed onychomycosis. The study evaluates the frequency of total nail dystrophy due to mixed onychomycosis in a hospital in Guatemala. The study is an observational prospective one conducted for five months. Nail clippings were collected from patients with total nail dystrophy and onychomycosis. The etiological agents were identified by SDA and mycosel agar. Out of 130 patients, 32 had mixed onycho­

mycosis. The study found most common age group is between 40 and 60  years. Diabetes had a strong association with onychomycosis. Blood glucose level more than 300 mg/dL will have a definite fungal disease. About 68% had concomitant tinea pedis. Trauma was seen in 25% of cases. The most common association found was T. rubrum + M. canis, T. rubrum + Candida and T. rubrum + opportunistic fungi. Twenty five percent has mixed onychomycosis. Cutaneous dermatophytosis is the main comorbidities associated with total nail dystrophy.

Key Messages €€ The most common association found was T. rubrum + Candida in mixed onychomycosis €€ Diabetes had a strong association with onychomycosis.

ARTICLE 26

In vitro Antidermatophytic Activity and Cytotoxicity of Extracts Derived from Medicinal Plants and Marine Algae Sit NW, Chan YS, Lai SC, et al. In vitro antidermatophytic activity and cytotoxicity of extracts derived from medicinal plants and marine algae.

Journal de mycologie medicale. 2018;28(3):561-7.

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28 Year Book of Dermatology – 2019 Fungal Infections Abstract The study evaluated the antifungal activity of 48 extracts from medicinal plants and marine algae against T. interdigitale and T. rubrum. The cytotoxicity was assessed using African monkey kidney epithelial cells. The medicinal plant extracts have better antifungal activity compared to marine algae.

COMMENT Certain medicinal plants and marine algae have anti fungal activity. The study compared the antifungal activity of forty eight extracts from medicinal plants and marine algae against T. interdigitale and T.  rubrum. Medicinal plants such as Melastoma malabathricum, Cibotium barometz, Rhapis excelsa, Muehlenbeckia platyclada, Syzygium myrtifolium were evaluated for antifungal activity. Marine algae such as Caulerpa sertularioides and Kappaphycus alvarezii were evaluated for antidermatophytic property. The antifungal activity was tested against T. interdigitale, T. rubrum and T. tonsurans. Colourimetric broth microdilution method were used to assess the anti dermatophytic

activity.The cytotoxicity was assessed using African monkey kidney epithelial cells. Neutral red uptake assay was used to measure the viability of Vero cells. V. amygdalina, K. alvarezii and C. sertu­ larioides extracts showed anti fungal activity against Trichophyton species. Minimum fungicidal concentration were recorded against T .rubrum and T. interdigitale. Medicinal plant extracts showed a higher anti dermatophytic activity compared to marine algae extracts. The leaves of medicinal plants such as Syzygium myrtifolium and Rhapis excelsa,  are considered to be potential source of antifungal activity against Trichophyton species.

Key Messages €€ Medicinal

plant extracts showed a higher antidermatophytic activity compared to marine algae extracts €€ The leaves of Syzygium myrtifolium and Rhapis excelsa,  are considered to be budding source of antifungal activity against Trichophyton species.

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Section 1: Epidemiological Studies

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ARTICLE 27

Magnitude and Associated Risk Factors of Superficial Skin Fungal Infection Among Primary School Children in Southern Tanzania Chikoi R, Nyawale HA, Mghanga FP. Magnitude and associated risk factors of superficial skin fungal infection among primary school children in Southern Tanzania.

Cureus. 2018;10(7):e2993.

Abstract Dermatophytosis is a common disease present worldwide. The study evaluates the risk factor, clinical and epidemiological profile of superficial skin infection in primary school going children in Southern Tanzania. Tinea capitis tops the list among the superficial skin infection. The important contributing factor found to be sharing of bed. Health education programs are needed to reduce the long term infection and impact on socioeconomic status.

COMMENT Dermatophytosis is often neglected communicable diseases in most of the developing countries. The study evaluates the risk factor, clinical and epidemiological profile of superficial skin infection in primary school going children in Southern Tanzania. The study is a descriptive, cross-sectional community based one conducted in a public primary school in Southern Tanzania. The sample size was about 500. The point prevalence of the dermatophytosis was about 35%. Tinea capitis tops the list among the superficial skin infection. Sharing of bed was found to be the most important contributing factor. Tinea corporis ranks second in the list. About 8% has multiple dermatophytic infections. Surprisingly girls are more prone for superficial fungal infections than boys. This

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differ from other countries were boys acquire more fungal infections. It would be because of girls engaged in more household activities thereby acquiring more fungal infections. Dermatophytic infections are more prevalent in low socioeconomic status, overcrowding, lack of personal hygiene, low level of education. Children of working parents tends to develop more infection compared to their counterparts this would be because of lack of proper care. The limitation of the study is it has included students from only one public school and it didn’t include private school, so the results won’t represent the general population. More studies are needed to analyze the superficial fungal infection in the private school. Health education programs are needed to reduce the long-term infection and impact on socioeconomic status.

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30 Year Book of Dermatology – 2019 Fungal Infections Key Messages €€ Tinea capitis tops the list among the superficial skin infection in public school in Southern Tanzania €€ Health

education programs are warranted to reduce the long-term fungal infection and impact on socioeconomic status.

ARTICLE 28

The Efficacy and Safety of Eberconazole Nitrate 1% and Mometasone Furoate 0.1% w/w Cream in Subjects with Inflamed Cutaneous Mycoses Rao G, Kumar AS, Carol F, et al. The Efficacy and Safety of Eberconazole Nitrate 1% and Mometasone Furoate 0.1% w/w Cream in Subjects with Inflamed Cutaneous Mycoses.

Reviews on Recent Clinical Trials. 2015;10:161.

Abstract In cases of inflamed cutaneous mycosis, the use of topical antifungals in combination with topical steroids provide rapid relief from the inflammation and also provides symptomatic relief. This study was conducted to evaluate the efficacy and safety of eberconazole nitrate with mometasone furoate cream in patients with inflamed cutaneous mycosis. The results showed that the combination of the drugs showed good efficacy and safety in the treatment of inflamed cutaneous mycosis.

COMMENT The usage of topical steroids in the treatment of cutaneous mycosis is controversial. The usage of steroids is not routinely advocated in all cutaneous mycosis. Steroids can be used when there is associated inflammation associated with the mycosis due to application of irritants and other home remedies. When the mycosis is associated with inflammation, usage of antifungals alone will not provide relief though the literature says that some antifungals have anti-inflammatory properties along with it.

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This multicentric, noncomparative study describes the safety and efficacy of eberconazole and mometasone in subjects with inflamed cutaneous mycosis. The study population were advised to apply the combination cream for 21 days and followed after. The results showed that there was significant reduction in symptoms and erythema and there was no treatment failure reported with this therapy. The drug gave good response in 70% of cases and adverse events noted in 27% of the

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Section 1: Epidemiological Studies cases, which were not serious. The serum cortisol level was noted low in 5% of the cases and significantly decreased in three patients.

31

The study shows that combination therapy offers symptomatic relief in inflamed cutaneous mycosis and there is increased compliance with this technique.

Key Message €€ Combination

of eberconazole and mometasone furoate showed good efficacy and safety in the treatment of inflamed cutaneous mycosis.

ARTICLE 29

Study of Prevalence of Dermatophytes Among Human Immunodeficiency Virus/AIDS Patients in Shadan Institute of Medical Sciences and Teaching Hospital and Research Centre, Hyderabad, Telangana, India Ali SY, Gajjala SR, Akhilesh R. Study of prevalence of dermatophytes among human immunodeficiency virus/AIDS patients in Shadan Institute of Medical Sciences and Teaching Hospital and Research Centre, Hyderabad, Telangana, India.

Indian Journal of Sexually Transmitted Diseases and AIDS. 2018;39(2):98-101.

Abstract Human immunodeficiency virus with associated immunodeficiency increases the risk of infectious disease including superficial fungal infection. The study evaluates the prevalence of dermatophytes among AIDS patient in a teaching hospital in Telangana. The study assessed the CD4+ count and test for dermatophytic infections. Tinea cruris is the most common dermatophytic infection. The most common etiological agent encountered is Trichophyton rubrum.

COMMENT Human immunodeficiency virus with associated immunodeficiency escalates the possibility of infectious disease including

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superficial fungal infection. The study assesses the prevalence of dermatophytes among AIDS patient in a teaching hospital in Telangana.

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32 Year Book of Dermatology – 2019 Fungal Infections The study population includes about 100 and 20 HIV positive patients. Out of which 38 patients had superficial fungal infection. Most of the patients were in the second and third decade. The most common dermatophytic infection seen in HIV individual was tinea cruris. This was not consistent with Aly et al. and Kaviarasan et al. who found most common dermatophytosis to be tinea pedis and tinea corporis respectively.

The most common etiological agent encountered is Trichophyton rubrum. The clinical presentation of dermatophytosis in HIV individual is found to be, multiple, disseminated and atypical lesion. The study assessed the CD4+ count and test for dermatophytic infections. The CD4 count does not influence the occurrence of dermatophytosis. Optimum treatment is essential for the dermatophytosis in HIV individuals.

Key Messages €€ Dermatophytosis in HIV individuals has diversity of clinical aspects €€ Trichophyton rubrum is the most common pathogen.

ARTICLE 30

Epidemiological Characteristics of Tinea Pedis in Military Kintsurashvili N, Galdava G. Epidemiological characteristics of tinea pedis in military.

Georgian Medical Journal. 2018;3(2):8-11.

Abstract Tinea pedis is one of the common superficial fungal infections that affect people of all sex and ages worldwide. Seventy percent of people have this infection once during their life time. The study has analyzed the epidemiological characteristics of tinea pedis in military personnel.

COMMENT Tinea pedis affects almost all age and sex. About 70% of people have acquired this infection once during their life time. The review article has evaluated the epidemiological characteristics of tinea pedis in military personnel.

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Trichophyton rubrum, Epidermophyton floccosum and Trichophyton mentagrophytes are the important fungal species that causes tinea pedis. The predisposing factors are young male, warm and humid climate, increased physical activity, excessive

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Section 1: Epidemiological Studies sweating, prolonged wearing of covered shoes, use of swimming pool and sharing of common towels. The military personnel are at high risk of tinea pedis because of increased physical activity and long-term use of covered shoes. The risk of spreading tinea pedis infection is common among military personnel.

33

The research has found out that compared to the civilians, tinea pedis is increasingly higher in military personnel. This would be because of their job nature. The prevalence of tinea pedis differ between military branches and military personnel ranks. Those military personnel in the lower rank are more prone compared to their higher officials.

Key Messages €€ Compared to the civilians, tinea pedis is increasingly higher in military personnel €€ Increased

physical activity and long-term use of covered shoes are risk factors for tinea pedis in military personnel.

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Section 2: Diagnostic Studies ARTICLE 1

Onychomycosis Infections: Do Polymerase Chain Reaction and Culture Reports Agree? Gupta AK, Nakrieko KA. Onychomycosis infections. Do polymerase chain reaction and culture reports agree?

J Am Podiatr Med Assoc. 2017;107(4):280-6.

Abstract The diagnosis of dermatophytes are mostly clinical and in cases of doubt, fungal culture is performed. But fungal culture is not feasible in all cases because of the slower processing and high false negative results and complicated by nondermatophytic mould infections. This study was performed to ascertain the correlation between PCR and fungal culture results. The results showed that fungal culture showed more false negatives compared to PCR.

COMMENT Fungal culture are the mainstay of investi­ gation in cases of fungal infections either superficial or deep. The disadvantage of fungal culture is that the process is laborious, requires proper clean methods of collecting samples and takes a long time for growth. In addition to the above factors, the fungal culture results have a high degree of false negative results. Because of the above shortcomings, the need for other investigations arose and lead to the use of PCR as the faster investigation in the diagnosis of onychomycosis. This study was performed to assess the agreement between culture and PCR for the diagnosis of suspected cases of

onychomycosis. The nail samples from the affected cases of onychomycosis was collected single time for some patients and repeat samples were collected from a small group of patients. The results showed that a fair correlation was present between the two methods in the diagnosis of dermatophytes compared to non dermatophytic moulds. In order to avoid false negative results in cases of NDM, repeat sample collection can help in improving the diagnosis of NDM. This study showed that PCR can be used for the rapid diagnosis in cases of onychomycosis and to differentiate from other conditions.

Key Message €€ The

study shows that fair correlation between PCR and culture was present in diagnosis of dermatophytic infections compared to non-dermatophytes.

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Section 2: Diagnostic Studies

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ARTICLE 2

Morphological Effect of the New Antifungal Agent ME1111 on Hyphal Growth of Trichophyton Mentagrophytes, Determined by Scanning and Transmission Electron Microscopy Nishiyama Y, Takahata S, Abe S. Morphological effect of the new antifungal agent ME1111 on hyphal growth of trichophyton mentagrophytes, determined by scanning and transmission electron microscopy.

Antimicrob Agents Chemother. 2016;61(1):e01195-16.

Abstract A new antifungal agent ME1111 is being researched for any effect on the morphology and bring out any structural changes of the hyphae of the dermatophyte Trichophyton mentagrophytes. It was observed that after treatment with the drug structural changes like formation of pits on the cell surface and dissolution of the intracellular organelles was observed.

COMMENT This study was performed to assess the antifungal effect of the new drug ME1111 on the ultra structure of T. mentagrophytes in a liquid medium and studied using scanning and transmission electron microscopy. The drug acts on the mitochondrial electron transport system thereby leading to changes in the intracellular organelles and leading to subsequently cell lysis. Trichophyton mentagrophytes was grown in culture and when the conidia was most abundant it was transferred to a liquid medium and sub-MIC and MIC of the drug ME1111 was added and incubated and later after 24 hours the sample was prepared for examination under the microscope. The results observed was there was both time and dose dependant deterioration on the hyphal structure with the drug. No changes was observed when the samples

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were examined after 4 hours of inoculation with the drug but after 8 hours changes like pit formation was observed and later after 24 hours there was complete cell lysis. The mechanism of action of this drug is that it inhibits the enzyme succinate dehydro­ genase, an enzyme important in ATP synthe­ sis which is the fuel for all cellular activities. In this study it was observed under scanning electron microscope that the conventional antifungal agents caused thickening of hy­ phae and accumulation of intermediates of sterol metabolism whereas the new agent caused plasmolysis, disintegration of cellular organelles and finally leading to cell mem­ brane damage and cell death. The results of this study shows promising antifungal effect of the new drug ME1111 but human studies are required for side effect profile and any in­ teraction with the human cells.

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36 Year Book of Dermatology – 2019 Fungal Infections Key Message €€ It was observed that after treatment with the drug structural changes like formation of pits on the cell

surface and dissolution of the intracellular organelles was observed.

ARTICLE 3

Development and Evaluation of Indirect Enzyme Linked Immunosorbent Assay for the Serological Diagnosis of Microsporum Canis Infection in Humans Aruna GL, Ramalingappa B. Development and evaluation of indirect enzyme linked immunosorbent assay for the serological diagnosis of Microsporum canis infection in humans.

J Mycol Med. 2018;28(2):285-8.

Abstract This study was conducted to evaluate the role of indirect ELISA as a serological assay for the detection of Microsporum canis infections in humans. The results show that indirect ELISA could be used as a sensitive, specific assay for the rapid diagnosis of Microsporum canis infections in humans.

COMMENT Microsporum canis is a zoophilic organism causing dermatophytosis. The main feature of zoophilic dermatophyte infections is the inflammatory reactions associated with it because of the hydrolytic enzymes produced by them. This infection is spread to humans through contact with domestic animals like cats and dogs. The inflammatory reaction due to this zoophilic species can mimic bacterial infections and can be misled and hence proper diagnosis of this is required. The current diagnostic measures for the identification of fungal organisms are either

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nonspecific or time consuming, hence the need for other faster, sensitive and specific investigations are required. The usage of indirect ELISA in the diagnosis of Microsporum canis infections is described in this study. The blood samples from suspected M.  canis infection was collected from the patients and the antigens were prepared and purified and the procedure was performed. The results show that this method has good sensitivity and specificity in the diagnosis of M. canis infections. The advantage of this technique is that the assay is quicker and can

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Section 2: Diagnostic Studies be used for processing large samples as in epidemiological studies. The application of the same principle can be used for the diagnosis

37

of other species of dermatophyte and deep fungal infections are to be researched for the earlier treatment of these fungal infections.

Key Message €€ Results of this study shows that indirect ELISA has good sensitivity and specificity in the diagnosis of

M. canis infection.

ARTICLE 4

Clinical Evaluation of β‐tubulin Real‐time PCR for Rapid Diagnosis of Dermatophytosis, a Comparison with Mycological Methods Motamedi M, Mirhendi H, Zomorodian K, et al. Clinical evaluation of β-tubulin real-time PCR for rapid diagnosis of dermatophytosis, a comparison with mycological methods.

Mycoses. 2017;60:692-6.

Abstract This study was performed to compare the real time PCR technique with the conventional methods for detection of fungi like direct microscopy and culture. The samples collected from the patients were subjected to direct microscopic examination, culture and real time PCR technique. The results showed that real time PCR increased the detection rate of dermatophytes compared to the other techniques.

COMMENT There are not many diagnostic techniques for detection of dermatophytes. The tech­ niques conventionally used are direct KOH examination and fungal culture. The other techniques like PCR can be used but it is not been studied much for the diagnosis of dermatophytosis. The use of PCR in the diagnosis of other disorders is well known but

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there is paucity of studies regarding the use of PCR in the diagnosis of dermatophytosis and hence this study was conducted to compare the current technique with other conventional procedures. The samples (scales) were collected from the patients and divided for the techniques like direct microscopy, culture and PCR

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38 Year Book of Dermatology – 2019 Fungal Infections technique. For the PCR technique the fungal DNA was isolated from the scales and purified and subjected to real time PCR technique. The results showed that the real time PCR significantly increased the detection rate of dermatophytosis compared to the other techniques. The drawback of the technique is that it is not available in all centers and the cost is high

compared to the other techniques and hence it is not advised for routine investigation of dermatophytosis but in cases where the disease is not responding and to confirm the diagnosis. Real time PCR cannot replace the conventional techniques in the diagnosis of dermatophytosis and further studies are required regarding the use in dermatophyte infections.

Key Messages €€ Real

time PCR significantly increased the detection rate of dermatophytosis compared to the other techniques €€ Real time PCR cannot replace the conventional techniques in the diagnosis of dermatophytosis.

ARTICLE 5

Polymerase Chain Reaction-restriction Fragment Length Polymorphism as a Confirmatory Test for Onychomycosis Lubis NZ, Muis K, Nasution LH. Polymerase chain reaction-restriction fragment length polymorphism as a confirmatory test for onychomycosis.

Open Access Maced J Med Sci. 2018;6(2):280-3.

Abstract Onychomycosis is the fungal infection of the nails caused by dermatophytes, yeasts and other non-dermatophyte organisms. Usually the diagnosis of onychomycosis is clinical but sometimes there is a need for diagnostic tests to differentiate form other disorders like psoriasis. But the tests available in the present era like the fungal culture takes a longer time to obtain results and hence there is a need for a faster and reliable test. This study was performed to assess the usage of PCR-RFLP as a confirmatory test for onychomycosis keeping fungal culture as a gold standard. The results showed that PCR-RFLP can be used as an alternative faster and accurate method in the diagnosis of onychomycosis.

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Section 2: Diagnostic Studies

39

COMMENT The present study was performed to evaluate the role of PCR-RFLP technique as a faster and accurate method in the diagnosis of onychomycosis compared to the gold standard fungal culture method. The samples collected were sent for both culture as well for PCRRFLP techniques. The results were evaluated in terms of the parameters like sensitivity, specificity, positive predictive value and negative predictive value respectively. The results showed that candidial onycho­ mycosis was more common followed by distal lateral subungual onychomycosis and the rare total dystrophic onychomycosis. The fungal species identified from PCR technique

was Candida albicans, Epidermophyton floccosum and Trichophyton tonsurans. This technique has a sensitivity of 86% compared to fungal culture. The specificity of the test is approximately 27%. The molecular diagnostic techniques yield results in 2–3 days’ time compared to fungal culture which takes 2–4 weeks. The positive predictive value of this technique is around 82% which is reasonably good. Various study compared in this article also show similar results. PCR-RFLP with its good sensitivity and positive predictive value can be used as an alternative in the diagnosis of onychomycosis.

Key Message €€ PCR-RFLP with its good sensitivity and positive predictive value can be used as an alternative in the

diagnosis of onychomycosis.

ARTICLE 6

Comparison of Photoinactivation of T. rubrum by New Methylene Blue (NMB) and Indocyanine Green (EmunDo®) Fekrazad R, Poorsattar Bejeh Mir A, Kahyaie Aghdam M, Ghasemi Barghi V. Comparison of photoinactivation of T. rubrum by new methylene blue (NMB) and indocyanine green (EmunDo®).

Photodiagnosis Photodyn Ther. 2017;18:208-12.

Abstract The search for new treatment options against dermatophytosis is being actively pursued due to the resistance shown by the organisms. This article portrays the use of photodynamic therapy with infrared and red light on the photosensitizing compounds like phenothiazinium dye and indocyanine green. The results showed that significant reduction in the growth of T. rubrum was observed after irradiation with red light. This opens a new gate for alternative therapeutic options for the treatment of dermatophytosis.

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40 Year Book of Dermatology – 2019 Fungal Infections COMMENT This study was conducted to determine whether the dermatophyte T. rubrum was inactivated following photoinactivation with infrared/red light therapy. The above therapy is a new therapeutic option for the treatment of dermatophytosis and can be tried in resistant cases of tinea when other options fail. In this study the cultured T. rubrum was subjected to photoinactivation by applying a photosensitizer substance phenothiazinium dye and indocyanine green and later exposing them to either infrared or red light and later

the suspensions were recultured and the colonies measured. The results showed that red light and indocyanine group had better results compared to the other groups. Overall the results were good when both photosensitizes were used and the results were good when red light was used compared to infrared dye. More in vivo studies are required regarding the use of this therapy in the treatment of dermatophytosis and should be researched for all organisms causing dermatophytosis.

Key Messages €€ Significant reduction in the growth of T. rubrum was observed after irradiation with red light €€ The results were good when both the photosensitizers were used and the results were good when red

light was used compared to infrared dye.

ARTICLE 7

A Simple but Yet Novel Stain in the Diagnosis of Onychomycosis Nargis T, Shenoy MM, Bejai V, Gopal V. A simple but yet novel stain in the diagnosis of onychomycosis.

Indian J Dermatopathol Diagn Dermatol. 2018;5:39-41.

Abstract Onychomycosis, clinically can resemble other conditions like psoriasis and other conditions and hence confirmation either by KOH examination or culture is required. This study was conducted to compare the efficacy between Chicago Sky Blue (CSB) stain in comparison with KOH technique. The results showed that CSB staining was more accurate in the diagnosis of onychomycosis and also the results were rapid.

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Section 2: Diagnostic Studies

41

COMMENT The clinical diagnosis of onychomycosis cab be difficult if the nails are the sole presentation of the disease without other skin lesions. In such case scenarios, further investigations like KOH examination is performed, but the technique is time consuming and it is difficult to visualise when KOH is used alone. So the use of other agents like Parker blue-black ink and Calcofluor white techniques can be utilized. This study was conducted to compare the efficacy of CSB stain with KOH in the diagnosis of onychomycosis. In this study, after clinical examination, cases of distal lateral subungal onychomycosis were selected and the subungual debris were collected. The collected samples were later subjected to KOH

examination. Later CSB stain was added and after 10 minutes the same slide was viewed by the dermatologist. The results showed that although much difference was not observed, the fungal elements stained deep blue colour when left for a long time. The advantage observed that when the keratin was not completely dissolved after KOH examination, the filaments stained properly after adding CSB stain. Also the results which came negative in KOH examination was positive after examination with the CSB stain. To conclude, CSB stain can be used routinely for the direct microscopic examination for its inexpensive, rapid and easy procedure which requires no expertise.

Key Message €€ Chicago sky blue stain can be used routinely for the direct microscopic examination for its inexpensive,

rapid and easy procedure which requires no expertise.

ARTICLE 8

Clinical Evaluation of the DermaGenius® Nail Real-time PCR Assay for the Detection of Dermatophytes and Candida Albicans in Nails Hayette MP, Seidel L, Adjetey C, et al. Clinical evaluation of the DermaGenius® Nail real-time PCR assay for the detection of dermatophytes and Candida albicans in nails.

Med Mycol. 2018.

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42 Year Book of Dermatology – 2019 Fungal Infections Abstract Onychomycosis, the fungal infection of the nail is caused by dermatophytes, yeasts like Candida and other non-dermatophyte organism. The investigations currently used like direct micro­ scopic examination and culture are time consuming and also have low sensitivity. To overcome this problem new diagnostic measure like molecular techniques are being increasingly used. This study was conducted to evaluate the role of DermaGenius, a PCR assay to detect the dermatophytes and Candida species causing onychomycosis. The results showed that the test has a high specificity and also yields faster results in the diagnosis of onychomycosis.

COMMENT This retrospective study was performed to evaluate the role of the molecular technique DermaGenius nail real-time PCR assay to detect the dermatophytes and candida albicans in nail disorders like onycho­ mycosis. The newer molecular techniques for the diagnosis of fungal infections is being used for their faster results and good specificity rates compared to the conventional techniques. The DermaGenius real-time PCR assay can detect the presence of Trichophyton rubrum, Trichophyton interdigitale and Candida

albicans in the nail specimens simultaneously. The finger and toe nail samples collected were subjected to the PCR technique while histo­ logy and culture techniques were compared. The results showed that the sensitivity and specificity of PCR technique was approximately eighty percent which is comparatively higher to conventional tech­ niques. The advantage of this technique is the faster results and high specificity. More studies comparing the conventional and PCR techniques are required in the diagnosis of fungal infections.

Key Message €€ DermaGenius

mycosis.

real-time PCR is a faster technique with high specificity in the diagnosis of onycho­

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Section 3: Management Studies ARTICLE 1

Copaiba Oil and Its Constituent Copalic Acid as Chemotherapeutic Agents against Dermatophytes Nakamura MT, Endo EH, Sousa JP, et al. Copaiba oil and its constituent copalic acid as chemotherapeutic agents against dermatophytes.

J Braz Chem Soc. 2017;28(8):1377-83.

Abstract Copaiba oil derived from Copaifera genus contains active compounds like copalic acid and acetocopalic acid which are used in the treatment of many diseases. This study was performed to assess the antifungal activity of these agents in the treatment of dermatophytosis. The study was performed to explore the uses of plant extracts in the development of new molecules for the treatment of dermatophytosis with less toxicity. The study results showed that copaiba oil had significant detrimental effect in the fungal cell wall synthesis and growth.

COMMENT Copaiba oil is a resin extracted from the trees found in tropical regions. The resin has antiinflammatory and fungicidal actions. The resin contains several compounds, important being sesquiterpenes and diterpenes of which copalic acid can be regarded as a marker for the Copaifera genus. New antifungal compounds with less toxicity and efficacy is the need of the hour. In this study the copaiba oil was extracted and refined from the source and tested with the dermatophyte strains Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum gypseum. The minimal inhibitory concentration was determined for the above species. The results were also analysed using scanning electron microscope and transmission electronic microscope.

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The results showed that copalic acid showed maximum antifungal activity compared to acetoxycopalic acid. The effects of this oil on the fungal elements were evaluated under fluorescence micro­ scope and the results showed reduction in the growth of hyphae and non-germinated conidia. The above compound also causes damage to the fungal cell wall. After treatment with the copaiba oil, T. menta­grophytes and M. gypseum showed significant damage to the cell wall and cytoplasmic membranes. The mechanism of the cell wall damage by the copaiba oil can be postulated to the change in the permeability of the cell wall leading to cell death. More research on this compound is required.

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44 Year Book of Dermatology – 2019 Fungal Infections Key Messages €€ Copalic acid showed inhibitory effect on the growth of the fungus €€ Copalic acid is the most active component in the copaiba oil €€ This compound can be further researched and can pave the way for new antifungal with less cost and

more efficacy.

ARTICLE 2

Inhibition of Dermatophytes by Photodynamic Treatment with Curcumin Brasch J, Wolf FS, Jendroschek BV, et al. Inhibition of dermatophytes by photodynamic treatment with curcumin.

Med Mycol. 2017;55(7):754-62.

Abstract The treatment of dermatophytosis with the current available drugs has become difficult because of the emerging resistance to the drugs. The availability of new drugs with fungicidal action is required to tackle the problem and to cut short the duration of the treatment and also to decrease the cost of the drugs. This study was performed to study the effect of curcumin with photodynamic treatment in the inhibition of the growth of dermatophytes. The result was favorable as there was inhibition of fungal growth depending upon the concentration of curcumin.

COMMENT Dermatophytosis is a common disease parti­ cularly in areas of humidity like the coastal regions. The current agents for the treatment of tinea infections are mainly fungistatic except for terbinafine, though resistance to terbinafine is frequently encountered these days. The development of new drugs are in the horizon. Photodynamic therapy with other photosensitising agents have been tried, with

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curcumin recently has shown its photoactive antimicrobial effect. Curcumin, a spice is used in culinary for its color and flavor all over the world particularly in India. This in vitro study was performed to determine the inhibitory effect of curcumin on the fungal growth. The specimen was collected from patients attending dermatology department and the dermatophytes were cultivated in

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Section 3: Management Studies sabrouraud’s dextrose agar till the conidia are sufficiently produced after which it was used as an inoculum for the curcumin and photodynamic treatment. In the meantime, curcumin after purification was divided into four different concentrations and it was made sure that it is not exposed to light during the whole procedure. The conidia were then inoculated with the different concentrates of curcumin and a control for each plate was kept. After this procedure only one plate was exposed to light of 367 nm and no heating of the suspensions was done. After this treatment the wells were loaded with sabouraud’s glucose broth to find

45

out the rate of fungal growth after the above process. The results showed that curcumin alone, that too in its highest concentration was effective against only Microsporum gypseum whereas the other species were not inhibited. Also the inhibitory effect of curcumin plus photodynamic treatment was most effective when the concentration of curcumin is the highest. The drawback of this study is the small sample size and more research is required to prove the above results. The same result cannot be applied in the topical curcumin and photodynamic treatment because of the bright yellow color which may not be accepted by all.

Key Messages €€ Curcumin alone in high concentrations effective against M. gypseum only €€ Curcumin

effective.

in combination with photodynamic therapy especially in high concentrations was highly

ARTICLE 3

Antifungal Efficacy of Amphotericin B against Dermatophytes and its Relevance in Recalcitrant Dermatophytoses: A Commentary Sinha S, Sardana K. Antifungal efficacy of amphotericin B against dermatophytes and its relevance in recalcitrant dermatophytoses: A commentary.

Indian Dermatol Online J. 2018;9(2):120-2.

Abstract Dermatophytosis is a common health problem in developing nations like India where high humidity and high temperature is seen. Usually, the condition responds to topical therapy if localized and systemic therapy if extensive. Recently, the organisms are not responding primarily

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46 Year Book of Dermatology – 2019 Fungal Infections to the treatment and relapses are frequently found and some cases are recalcitrant to the treatment from the beginning. This article provides data that amphotericin B can be used as topical formulations but cannot be considered superior to terbinafine but can be considered in recalcitrant cases.

COMMENT The treatment of dermatophytosis ranges from topical azoles and terbinafine to oral triazoles like fluconazole and itraconazole, allylamine derivatives like terbinafine and griseofulvin. The susceptibility of the organisms to the drugs varies and resistance due to clinical or microbiological. Resistance to terbinafine has been reported and even to topical agents, so clinicians have resorted to usage of agents like amphotericin B though it is not FDA approved. The formulation of amphotericin B is in lipid formulation for easier penetration into the stratum corneum. This drug is a broad spectrum antifungal agent usually used for disseminated invasive mycosis. Due to its poor oral bioavailability, phospholipid based formulations are available for good absorption as well as well as to decrease side effects. No study has been performed regarding the

efficacy of amphotericin B in the treatment of dermatophytosis. In vitro studies have shown that ampho­ tericin B has shown good results against Trichophyton rubrum and verrucosum. The drug was inferior to terbinafine in its action against T. mentagrophytes and E. floccosum. But the data cannot be applied when it is tested in patients as the in vitro susceptibility results cannot be applied to in vivo. The available data shows that ampho­ tericin B is effective only secondary to terbinafine and echinocandins. Topical amphotericin B is not advocated for first line dermatophytic infections but can be used in recalcitrant cases. It should be selectively used and distribution of the drug should be based on prescription because this drug is effective and used as induction regimen in cases of invasive fungal infections.

Key Messages €€ Amphotericin B is effective secondary to terbinafine and echinocandins €€ Amphotericin B topical is not advocated as the first line treatment for dermatophytic infections but

can be used in recalcitrant cases.

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Section 3: Management Studies

47

ARTICLE 4

A Review of the Most Effective Medicinal Plants for Dermatophytosis in Traditional Medicine Sepahvand A, Eliasy H, Mohammadi M, et al. A review of the most effective medicinal plants for dermatophytosis in traditional medicine.

Biomed Res Ther. 2018;5(6):2378-88.

Abstract Fungal infections are seen all over the world and more commonly observed in developing nations. The treatment of the fungal infections with the antifungal agents used orally have side effects and laboratory tests have to be performed especially in usage of drugs like amphotericin  B. This article describes the usage of medicinal plants in the treatment of dermatophytosis.

COMMENT Fungal infections can be classified into superficial fungal infections, subcutaneous mycoses and deep fungal infections. Fungal infections are seen in both immuno­­competent as well as immune suppressed individuals, though the latter group suffers from dis­ seminated and treatment resistant infections. The drugs commonly used for these infections are amphotericin B, flucytosine, the azole antifungals, terbinafine and echinocandins group of drugs. Drugs like amphotericin B are used for treatment induction and not for maintenance because of the side effect profile also for the development of resistance. To combat these problems the search for new drugs based on less side effect profile is on the rise and the research on botanicals in the treatment of fungal infections is being pursued actively.

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This review article collected data regarding botanicals having antifungal property from online data and compiled the results. The results showed that plants from Lamiaceae family have the antifungal property. Substances from the plants having antifungal activity are phenols, tannins, flavonoids and anthocyanins. Some of the antifungal compounds isolated are eugenol, tetranortriterpenoid, glycosidic saponin, carvacrol and thymol. Many more antifungal compounds isolated from botanicals have been mentioned in this article. The antifungal compounds isolated from these botanicals are comparatively safer and cheaper and more research studies with in vivo activity is required.

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48 Year Book of Dermatology – 2019 Fungal Infections Key Messages €€ Compounds derived from Lamiaceae family have antifungal property €€ Compounds

having antifungal property are eugenol, tetranortriterpenoid, glycosidic saponin, carvacrol and thymol.

ARTICLE 5

Investigation of the Antifungal Potential of Linalool Against Clinical Isolates of Fluconazole Resistant Trichophyton rubrum De Oliveira Lima MI, Araújo de Medeiros AC, Souza Silva KV, et al. Investigation of the antifungal potential of linalool against clinical isolates of fluconazole resistant Trichophyton rubrum.

J Mycol Med. 2017;27(2):195-202.

Abstract This study was conducted to determine the antifungal action of the new compound Linalool, belonging to monoterpene group against the fluconazole resistant Trichophyton rubrum. The action of linalool and ketoconazole was evaluated at different concentrations of fungal elements. The results showed that linalool was effective as an antifungal agent against T. rubrum.

COMMENT Research on new antifungal agents are being performed and various botanicals and new compounds are being investigated. A compound linalool belonging to mono­ terpene group is being investigated for its antifungal action against T. rubrum. The minimal inhibitory concentration for linalool and ketoconazole was evaluated. Later the action of linalool and ketoconazole at different concentrations on the mycelial growth was

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performed. Resistance to fluconazole was found in the assay. The inhibition of mycelial growth was noticed when linalool and ketoconazole was tested. Also inhibition of conidia and conidial growth was noticed after treatment with linalool. There was damage to the cellular material after treatment with linalool. The end result was that the drug caused inhibition of fungal mycelial growth, formation of stunted

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Section 3: Management Studies and deformed hyphae. The results show that linalool is effective as an effective antifungal agent. More research has to be performed

49

regarding the safety of the drug. Human studies has to be performed to assess the above mentioned parameters of the drug.

Key Message €€ Linalool

is effective as an antifungal agent in view of its inhibition of fungal mycelial growth, formation of stunted and deformed hyphae.

ARTICLE 6

Fractional Carbon Dioxide Laser Assisted Delivery of Topical Tazarotene versus Topical Tioconazole in the Treatment of Onychomycosis Abd El-Aal EB, Abdo HM, Ibrahim SM, et al. Fractional carbon dioxide laser assisted delivery of topical tazarotene versus topical tioconazole in the treatment of onychomycosis.

J Dermatolog Treat. 2018;28:1-6.

Abstract Onychomycosis is the fungal infection of the nail caused by dermatophytes/non-dermatophyte organism. This study was conducted to determine the efficacy of topical tazarotene delivered by the fractional CO2 laser versus the topical application of tioconazole. The results also showed favorable results with the laser assisted delivery of tazarotene.

COMMENT The treatment of onychomycosis is challeng­ ing because the therapeutic options available have to be given for a longer period (months) depending upon the site (finger nails/ toe nails). The routinely used drugs like fluconazole/terbinafine/itraconazole are given as pulse therapies to minimize the side effect and also to increase the patient compliance. Only topical treatment is

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ineffective because the penetrance of the drug is hampered by the hardness of the keratin of the nail plate. This study was conducted to compare the efficacy of the topical retinoid tazarotene delivered by fractional CO2 assisted delivery versus the topical application of tioconazole. The study population was divided into two groups based on the administration of the

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50 Year Book of Dermatology – 2019 Fungal Infections drug and routine investigations for the fungus like direct microscopy and culture was performed. The results also showed favorable results in the group of patients who were administered tazarotene delivered by laser assisted ablative therapy compared to tioconazole. This shows

that the administration of the agents followed by ablative therapies like laser can enhance the penetration of the drug and leads to disease resolution. The advantage of this method is that the disease resolution is seen with topical therapies itself and hence systemic therapy can be avoided and is beneficial to the patient.

Key Message €€ Topical

tazarotene delivered after fractional CO2 laser ablation increases the curative rate of onychomycosis.

ARTICLE 7

Discovery of Antifungal Compounds from Kampo Medicine Against Dermatophytes Da X. Discovery of antifungal compounds from kampo medicine against dermatophytes.

Open Forum Infect Dis. 2017;4:S480.

Abstract Kampo medicine deals with the treatment of ailments with natural crude extracts from plants, animals and minerals. The compounds in kampo medicine have significant antimicrobial effects as plant extracts have significant amount of defensins. This study was performed to evaluate the antifungal effect of the compounds from kampo medicine against dermatophytes. The results showed that two compounds Baicalein and Wogonin have significant antifungal effects.

COMMENT This study was performed to determine the antifungal activity of the compounds used in kampo medicine against dermato­phytes. After adequate testing, it was found that 7 compounds from kampo medicine have significant antifungal effect against

sec-3_Management Studies_Article 1-41.indd 50

T.  rubrum. The active element having antifungal effect was Ougon, a crude extract from the roots of the plant Scutellaria. This study was performed to isolate the active elements contained in Ougon for antifungal effects.

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Section 3: Management Studies In this study, the dermatophytes tested were T. rubrum, T. mentagrophytes, A. fumigatus and C. albicans. The components were studied with spectrometry and chromatography techniques. The analysis revealed that two compounds named Baicalein and Wogonin have significant antifungal activity.

51

Baicalein was active against all the four organisms while Wogonin did not act against C. albicans. The mechanism of action of these compounds is postulated to act via the programmed cell death. Thus the results show that these compounds can be further researched for its antifungal properties in in vivo and other methods.

Key Messages €€ The analysis revealed that two compounds named Baicalein and Wogonin have significant antifungal

activity

€€ The mechanism of action of these compounds is postulated to act via the programmed cell death.

ARTICLE 8

Biosynthesized Silver and Gold Nanoparticles are Potent Antimycotics Against Opportunistic Pathogenic Yeasts and Dermatophytes Rónavári A, Igaz N, Gopisetty MK, et al. Biosynthesized silver and gold nanoparticles are potent antimycotics against opportunistic pathogenic yeasts and dermatophytes.

Int J Nanomedicine. 2018;13:695-703.

Abstract The drugs available for the treatment of fungal infections are limited and newer drugs are on the horizon. This study was performed to assess the role of nanoparticles of gold and silver as potent antimycotic agents against yeasts and dermatophytes. The results showed that Cryptococcus neoformans was susceptible to both the agents and had minimal effect on human keratinocytes.

COMMENT Fungal infections are commonly encountered all over the world but it is predominantly seen

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in regions of high humidity like the coastal regions and also in developing nations. The

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52 Year Book of Dermatology – 2019 Fungal Infections traditional antifungal drugs used are relatively safe but have developed the problem of resistance. The need for newer drugs like silver and gold particles are being extensively studied and the development of newer formulations using biological sources for nanoparticles are being done. Cell free extract from the yeast Phaffia rhodozyma can be utilised for the development of nanoparticles and hence the gold and silver nanoparticles can be developed.

The results showed that the above silver and gold nanoparticles were effective against Microsporum and Trichophyton organisms and inhibit Candida and Cryptococcus species. Among the organisms isolated, Cryptococcus neoformans was susceptible to both gold and silver nanoparticles and the compounds did not have any adverse effect on human keratinocytes. Future studies are needed for determining the safety and efficacy of silver and gold nano particles.

Key Messages €€ Silver and gold nanoparticles were effective against Microsporum and Trichophyton organisms and

inhibit Candida and Cryptococcus species.

ARTICLE 9

Triintsin, a Human Pathogenic Fungus-derived Defensin with Broad-spectrum Antimicrobial Activity Shen B, Song J, Zhao Y, et al. Triintsin, a human pathogenic fungus-derived defensin with broad-spectrum antimicrobial activity.

Peptides. 2018;107:61-67.

Abstract Antimicrobial agents can be derived from microorganisms because of the coadjuvant role between organism and also the competitive relationship to survive among the others. The fungal defensins have been proposed to have antimicrobial properties. This study was conducted to evaluate the antifungal effect of Triintsin, a defensin produced by T. interdigitale. The result showed that the substance was found to have antimicrobial activity against gram positive and gram negative bacteria as well as antifungal effect.

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Section 3: Management Studies

53

COMMENT This study portrays the antimicrobial actions of Triinstin, a defensin produced by the organism Trichophyton interdigitale. The anti­microbial agents are unique in the fact the substances are produced by the micro­organisms to survive in a competitive environment. Triintsin is a defensin produced by T. interdigitale and the genomic structure was analysed. The structure of Triintsin showed that it has a cysteine amino acid stabilised

by α-helical and β-plated structure. After the formation of three pairs of disulfide bonds triintsin was found to have significant antibacterial effects against gram positive and gram negative organisms and also antifungal effects. This shows that further research activities can be conducted to evolve the compound into an antifungal agent as the demand for newer antifungal agents is on the rise.

Key Message €€ Triintsin, a fungal defensin isolated from T. interdigitale has significant antibacterial effects against

gram positive and gram negative organisms and also antifungal effects.

ARTICLE 10

Onychomycosis in Children: Safety and Efficacy of Antifungal Agents Gupta AK, Mays RR, Versteeg SG, et al. Onychomycosis in children: Safety and efficacy of antifungal agents.

Pediatr Dermatol. 2018;35(5):552-9.

Abstract Onychomycosis is commonly encountered in adult population and rarely seen on children. The recent data has shown a rise in the number of cases of onychomycosis in children. This study was conducted to assess the efficacy and safety of antifungal agents used for the treatment of onychomycosis in children. The result showed that the current antifungal agents used for onychomycosis in children are safe with very minimal adverse events.

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54 Year Book of Dermatology – 2019 Fungal Infections COMMENT This study was performed by gathering information regarding studies on anti­ fungal agents used in the treatment of onychomycosis in children. The data was collected online database and seven studies were chosen. Onychomycosis is a fungal infection of the nail seen commonly in adults and its incidence in children is low. Recent studies have shown cases of onychomycosis in children on the rise. There is paucity of data regarding the usage of antifungal agents in children for onychomycosis adding to the

fact that none of the agent is FDA approved for treatment of onychomycosis in children. The results showed that antifungal agents used in the treatment of onychomycosis in children had minimal adverse effects. The study shows that the current agents are effective and safe for use in children for onychomycosis but with caution as they are not FDA approved. More randomized controlled trials are required regarding the efficacy ad safety of antifungal agents in the treatment of onychomycosis.

Key Message €€ Current antifungal agents are effective and safe for use in children for onychomycosis but should be

used with caution as they are not FDA approved.

ARTICLE 11

Anti-candidal Activity of Selected Analgesic Drugs Used Alone and in Combination with Fluconazole, Itraconazole, Voriconazole, Posaconazole and Isavuconazole Król J, Nawrot U, Bartoszewicz M. Anti-candidal activity of selected analgesic drugs used alone and in combination with fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole.

J Mycol Med. 2018;28(2):327-31.

Abstract Various compounds are being tested for their antifungal activity and in that category comes the evaluation of antifungal activity of analgesic drugs. This study was conducted to evaluate the antifungal activity of five analgesic drugs against triazole susceptible and triazole resistant candida species. The results showed that ibuprofen had antifungal effect compared to others and can be studied further regarding its antifungal activity.

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Section 3: Management Studies

55

COMMENT This study was conducted to evaluate the antifungal action of five analgesic drugs administered along with triazole susceptible and resistant candida species. The minimal inhibitory concentrations of the drugs was determined by microdilution method. The drugs which were tested were ibuprofen, acetaminophen, metamizole, meloxicam and acetylsalicylic acid. The results showed that among the five tested drugs, only ibuprofen showed anti­

fungal effect. When the drug was combined with triazoles three types of interaction was observed which are synergistic, indifference and antagonism. Posaconazole exhibited synergism with ibuprofen in few cases. Cases of antagonism between fluconazole and ibuprofen was observed when tested in species of C. glabrata and C. tropicalis. The overall results showed that ibuprofen shows antifungal effects and more research can be performed regarding the newly found use of the drug.

Key Message €€ The

results showed that ibuprofen had antifungal effect compared to others and can be studied further regarding its antifungal activity.

ARTICLE 12

Antifungal Resistance in Dermatology Pai V, Ganavalli A, Kikkeri NN. Antifungal Resistance in Dermatology.

Indian J Dermatol. 2018;63(5):361-8.

Abstract Fungal infections are commonly seen all over the world though developing nations are more affected by this. The treatment of fungal infections has become challenging due to non-response to treatment or resistance to the agent used. The resistance to a drug can be microbiological or clinical. Microbiological resistance can be due to factors in fungi causing genetic alteration leading to decreased response to the drug. Clinical resistance can be due to host factors or factors related to drug. Combination antifungal treatment can provide synergistic action and decrease the resistance.

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56 Year Book of Dermatology – 2019 Fungal Infections COMMENT Dermatophytes are keratinophilic fungi belonging to the three genera, Epidermo­phyton, Microsporum and Trichophyton. The fungus enters the body when favorable condition like barrier dysfunction, increased sweating, macera­tion and immunodeficiency promote the entry of the organisms. The antifungal drugs can be classified briefly into azole derivatives, allylamine derivatives, heterocyclic benzo­ furans, echinocandins and polyene derivatives. The most commonly used drugs belong to azole and allylamine derivatives. The problem of fungal resistance has become rampant due to improper usage of the drugs particularly in the immunocompromised. The causes for fungal resistance can be due to inability of the drug to get concentrated inside the cell, decreased affinity of the drug to the fungus, biofilm production. The host factors like immunosuppression, site and extent of involvement can play a role. Drug factors like dosage, pharmacokinetics interactions can play a role in resistance.

Microbiological resistance can be primary/secondary. Primary resistance can be consi­dered when the fungus is not responding to the agent from the start whereas secondary resistance is considered when the organism was initially susceptible to the drug but later does not respond to it. Clinical resistance is considered when the failure of eradication of the organism despite it showing in vitro susceptibility to the agent. To combat resistance patient education regarding hygiene, proper adherence to treatment must be explained. The combination of antifungal agents can be tried for synergistic effect. Combination with nonantifungal agents like tacrolimus, simvastatin, proton pump inhibitors and other immunomodulatory agents. Fractional carbon dioxide laser combined with topical agents can be tried for localised disease not responding to the above management.

Key Messages €€ Microbiological

resistance can be due to factors in fungi causing genetic alteration leading to decreased response to the drug €€ Clinical resistance can be due to host factors or factors related to drug €€ The combination of antifungal agents can be tried for synergistic effect.

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ARTICLE 13

Antibiofilm Treatment for Onychomycosis and Chronic Fungal Infections Gupta AK, Carviel J, Shear NH. Antibiofilm Treatment for Onychomycosis and Chronic Fungal Infections.

Skin Appendage Disord. 2018;4:136-140.

Abstract Onychomycosis is a difficult to treat fungal infection of the nails. The antifungal agents given for the treatment of onychomycosis are to be administered for a longer duration and if the biofilm formation is present there is little/no effect in the treatment. For the treatment to be effective, biofilms must be disrupted prior to antifungal therapy. Other therapies like photodynamic therapy, lasers can be tried along with the antifungal therapy for good results.

COMMENT The therapy for onychomycosis is difficult for the presence of hard keratin in the nail thereby topical agents would not penetrate easily and hence systemic agents are to be given. The systemic agents useful are terbinafine, itraconazole and fluconazole. The above agents can be administered either as daily doses or monthly pulse therapy. The response to sole systemic antifungal agents is challenged by the formation of biofilms by the fungus. The usage of new options like photodynamic therapy and lasers like fractional CO2 laser/diode laser can be used along with antifungal therapy thereby increasing the penetration of the agents. The reasons for the decreased suscepti­ bility of antifungal agents to the organisms is either due to chronicity and virulence of the causative agent. It has been proposed that expression of multidrug efflux pump by the fungus can lead to resistance to the drugs.

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The biofilms once formed has to be surgically removed as they bind strongly to the surface and also they form extracellular matrix (ECM) leading to treatment failure. Therefore prior to treatment the ECM must be disrupted with agents like povidone iodine, lactic acid and amylase enzymes. Some of the agents shown to disrupt biofilms are DNase 1, α-amylase, combination of lactic acid and cetrimide and chitosan. After the disruption of the biofilm, other therapies like photodynamic therapy, low frequency surface acoustic waves and lasers can be used along with antifungals for their increased penetration. The article concludes that if any case of mycologically proven cases of onychomycosis is not responding to the therapies, biofilm formation must be considered and treatment must be done to disrupt the biofilm and the other therapies above mentioned can be given for complete recovery.

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58 Year Book of Dermatology – 2019 Fungal Infections Key Message €€ In cases of mycologically proven onychomycosis not responding to the antifungal therapies, biofilm

formation must be considered and treatment must be done to disrupt the biofilm for complete resolution.

ARTICLE 14

Newer Topical Treatments in Skin and Nail Dermatophyte Infections Sahni K, Singh S, Dogra S. Newer Topical Treatments in Skin and Nail Dermatophyte Infections. 

Indian Dermatol Online J. 2018;9(3):149-58.

Abstract The need for new antifungal agents is on the rise due to the increased number of recurrent/ chronic cases. Also, the resistance to the antifungal agents is commonly observed. This has led to the research of new agents to combat the above problem. The rising cost of treatment due to the new drugs also has emerged as the new problem as many in the developing nations would not afford to the treatment. Also newer modalities like lasers and photodynamic therapy are also being tried for cases of recalcitrant limited infections. This article provides data regarding the new treatment options for the treatment of dermatophytosis.

COMMENT Superficial fungal infections are caused by the dermatophytes belonging to the genera Trichophyton, Epidermophyton and Microsporum. Chronic dermatophytosis is defined when the lesion persists even with adequate treatment for 6 months to 1 year. Recurrent dermatophytosis is defined when there is recurrence of lesions few weeks after stopping treatment. Various factors like host, agent, environ­ mental and topical steroid abuse has led to the problem of chronic and recurrent

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dermatophytosis. To combat the above problem, newer agents with great efficacy and less side effects are being researched. The antifungal agents currently used belong to the azoles, allylamines, morpholines, polyenes and others. Apart from the regular imidazole agents, newer agents are being developed. The few newer agents are Lanoconazole and Efinaconazole. Efinaconazole is effective against dermatophytes, nondermatophyte moulds and Candida species. Pramiconazole

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Section 3: Management Studies is newer agent under development having good in vitro and in vivo activity against dermatophytes, Candida and Malassezia species. Some of the new antifungals under the research activity are arasertaconazole, BB2603, ME1111, hydroxychavicol and phlorotannins. Some of the novel agents are tavaborole, topically approved for the treatment of onychomycosis. The advantage

59

of the drug is that it has a low molecular weight leading to increased penetrance into the nail. Mycological cure is less compared to antifungal agents but can be useful as an adjunctive therapy. Photodynamic therapy and laser thera­ pies can be tried for localised recalcitrant dermatophytosis. Older drugs like ampho­ tericin B in topical formulations are being used for resistant and recurrent infections.

Key Messages €€ New antifungals under the research activity are arasertaconazole, BB2603, ME1111, hydroxychavicol

and phlorotannins

€€ Photodynamic therapy and laser therapies can be tried for localized recalcitrant dermatophytosis.

ARTICLE 15

Flavonoids from Plinia cauliflora (Mart.) Kausel (Myrtaceae) with Antifungal Activity Souza-Moreira TM, Severi JA, Rodrigues ER. Flavonoids from Plinia cauliflora (Mart.) Kausel (Myrtaceae) with antifungal activity.

Nat Prod Res. 2018;5:1-4.

Abstract Research for new antifungals has extended to plant extracts as various studies have shown promising antifungal activity. This study was conducted to evaluate the antifungal activity of the plant Plinia cauliflora and kausel. The results showed that the isolated ethyl acetate fraction, quercetin and myricetin showed good activity against Candida species in particular C. krusei, C. parapsilosis and dermatophytes T. rubrum and M. canis. The results were promising enabling further research on these compounds.

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60 Year Book of Dermatology – 2019 Fungal Infections COMMENT This study was performed to evaluate the antifungal effect of the flavonoid compounds from Plinia cauliflora. The fruit of this plant is edible and few studies have shown that the plant extracts have antifungal activity. This study was performed with the purified extract of the leaves of this plant and the extract was obtained in 70% alcohol. The isolated compounds quercetin and myricetin were tested for antifungal activity against Candida, dermatophytes and nondermatophyte moulds.

The results revealed that the extract showed good antifungal effect against candida species in particular C. krusei, C. parapsilosis and dermatophytes T. rubrum and M. canis. The isolated compound has minimal toxicity and was active against nondermatophyte moulds also. Hence, further research has to be promoted regarding the antifungal effects of this compound and also comparative studies with antifungal agents are to be done.

Key Message €€ Isolated

ethyl acetate fraction, quercetin and myricetin showed good activity against Candida species in particular C. krusei, C. parapsilosis and dermatophytes T. rubrum and M. canis.

ARTICLE 16

Biofilms and beyond: Expanding Echinocandin Utility Larkin EL, Dharmaiah S, Ghannoum MA. Biofilms and beyond: expanding echinocandin utility.

J Antimicrob Chemother. 2018;73:i73-81.

Abstract Echinocandins, the antifungal agent has been in use for more than 15 years and used for invasive candidial infections. The recent studies have shown a shift in the non-albicans species of candidiasis and also the species were not responding to fluconazole as compared to the Candida albicans. Since the drug is effective and safe, new uses for the drug was extended into the areas of biofilm formation. This article provides data regarding the performance of echinocandins in this new area of interest.

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COMMENT Caspofungin was the first echinocandin approved by FDA for treatment of invasive aspergillosis. Later use was extended to candidial infections. Later there was intro­ duction of two more two more drugs of echinocandins namely, micafungin and anidulafungin. These agents are currently used in the treatment of invasive candidiasis, esophageal candidiasis. The above agents are usually given as intravenous formulation as they have very poor oral bioavailability. These drugs inhibit 1,3-β-glucan synthesis of the fungal cell wall. The reported side effects are mild ranging from rash, nausea and vomiting. The newer azoles like voriconazole have side effects like hepatotoxicity and drug interactions whereas amphotericin B has nephrotoxicity. Compared to these drugs, echinocandins have minimal side effects which are usually tolerated. They have a broad spectrum of action against Candida species, and reasonable activity against Aspergillus species. Now, micafungin is being used for the prophylaxis in patients of immunosuppressed patients after transplant. The new echinocandins currently developed are rezafungin acetate and SCY-078. Rezafungin is a long-acting echinocandin given as once weekly IV infusion for invasive candidiasis. The advantage of the drug is the weekly administration increasing the compliance of the patients. SCY-078 is a semisynthetic triterpene antifungal administered orally for invasive and mucocutaneous fungal infections. It also has activity against biofilms

and is being investigated. The drug has shown good profile in its phase 1 trials and the drug had promising results in the phase 2 trials for invasive candidiasis. The other emerging use of echinocandins is their use in infections complicated by biofilm formation. Candida are part of normal microflora and in conditions favoring they lead to development of invasive infections and biofilm formation. Once invasiveness and biofilm formation occur in ill patients with indwelling catheters surgical removal of the biofilm is the therapy advocated. Other antifungal drugs are not effective against biofilm producing organisms. The mechanism of action of this drug and the relatively safe profile of this drug makes it a favorable option in treating biofilms. Echinocandins are presently considered in the treatment of mucosal candidiasis which is considered as a form of biofilm. Biofilms of the indwelling catheters and ventricular assist devices in the immuno­ compromised patients and children is quite difficult as catheters cannot be changed often and also the ventricular assist devices are not amenable for replacement/removal. Hence echinocandins are currently preferred for these conditions. This article gives a new insight in the treatment of fungal infections complicated by biofilm formation. Echinocandins can be used for those infections complicated by biofilms and use should be strictly regulated to prevent resistance.

Key Messages €€ Rezafungin acetate and SCY-078 are the new echinocandins available and are in their development

and are in their phase 2 trials

€€ Echinocandins are presently considered in the treatment of mucosal candidiasis which is considered

as a form of biofilm.

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62 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 17

Clinical Laser Treatment of Toenail Onychomycoses Zalacain A, Merlos A, Planell E, et al. Clinical laser treatment of toenail onychomycoses.

Lasers Med Sci. 2018;33(4):927-33.

Abstract Onychomycosis is difficult to treat dermatosis and newer modalities of treatment are being sought due to frequent failure with antifungal treatment. This study was conducted to assess the use of lasers in the treatment of onychomycosis. In this study, 1064 nm laser was used for the treatment of onychomycosis. The results showed that laser therapy showed good results for the treatment of onychomycosis but took few months for the complete clearance.

COMMENT Onychomycosis of the fingernails and toe nails differs in the aspect that the toe nail infections are not recognized by the patients early and they are prone to occlusive footwears and frequent microtrauma. The therapy for toe nail onychomycosis is rendered slow by the thick nail plates due to the disease process and also decreased vascularity in other pathological process associated with it. The antifungal treatment for onycho­ mycosis is not limited to oral antifungals. Systemic antifungals have to be administered for the adequate concentration of the drug to reach the target site. Usually, both topical and oral therapies are combined together for obtaining desired results though topical treat­ ment has to be prolonged for 6 months or more.

In this study the all patients with clinically suspected onychomycosis despite the fungal culture results were included. The patients were then given laser therapy and only antifungal powder was after treatment for daily application till next treatment session. The results showed that with the increase in the duration of treatment by approximately 6 months to acquire negative fungal culture results. All the patients had high degree of satisfaction with the treatment and there were no major adverse effects. This study shows that although sole laser therapy had good curative rates, the combination with topical antifungals lead to increased cure rates.

Key Message €€ The results showed that laser therapy showed good results for the treatment of onychomycosis but

took few months for the complete clearance.

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ARTICLE 18

Evaluation of Biofilm Formation Ability in Different Candida Strains and Anti-biofilm Effects of Fe3O4-NPs Compared with Fluconazole: An in vitro Study Salari S, Sadat Seddighi N, Ghasemi Nejad Almani P. Evaluation of biofilm formation ability in different Candida strains and anti-biofilm effects of Fe3O4-NPs compared with Fluconazole: an in vitro study.

J Mycol Med. 2018;28(1):23-8.

Abstract The formation of biofilms by the fungal strains lead to difficulty in treating the underlying condition. Various medical treatments have been tried for the treatment of the same but not all are promising. This study was conducted to evaluate the antibiofilm effects of Fe3O4 nanoparticles on the biofilm forming capacity of various species of candida strains. The results showed that compared to fluconazole, the action of nanoparticles of Fe3O4 was lesser or not considered significant.

COMMENT Candida species have the ability to produce biofilms and they complicate the treatment leading to mortality. The risk is higher with the indwelling catheters and also in immunocompromised patients. This study was conducted to evaluate the role of nanoparticles of Fe3O4 on the biofilm forming candida species compared with fluconazole. The Fe3O4 particles were chosen because of the easy availability and low cost. The compound was compared with fluconazole for its action against the biofilm producing capacity of Candida species.

The results showed that among candida species, C. lusitaniae had the highest biofilm forming capacity compared with others. The biofilms produced by C. albicans and C. parapsilosis was inhibited by Fe3O4 particles than fluconazole but the result was not significant. For the other species fluconazole gave better results than Fe3O4 particles. The effect on C. glabrata was equal for both the agents. This study shows that the antibiofilm action of Fe3O4 was not significant enough compared with fluconazole.

Key Message €€ The results showed that compared to fluconazole, the action of nanoparticles of Fe3O4 was less or not

considered significant.

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64 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 19

Luliconazole, A New Antifungal Against Candida Species Isolated from Different Sources Taghipour S, Kiasat N, Shafiei S, et al. Luliconazole, a new antifungal against Candida species isolated from different sources.

J Mycol Med. 2018;28(2):374-8.

Abstract Luliconazole is an azole derivative of antifungals. The study evaluates the susceptibility of luliconazole against candidal species. Candidal source were obtained from vulvovaginal candidiasis, tracheal secretions and neutropenic patients. In vitro analyse showed luliconazole can be an anticandidal agent.

COMMENT Luliconazole is an azole with wide spectrum antifungal by inhibiting 14α-demethylase. Lulico­ nazole is used in the treatment of pityriasis versicolor, dermatophytosis, onycho­ mycosis and mucocutaneous candidiasis. The study did a in vitro analyse of luliconazole against different sources of candidal agent. The study is appreciable that it has used variety of candidal sources such as vulvo­ vaginal candidiasis, tracheal secre­tions and neutropenic patients. In vitro luliconazole serial dilutions against many candida strains were done. Minimum inhibitory concentration (MIC) is the minimum quantity of drug

that is required to inhibit the growth of the organisms. MIC of luliconazole for Candida was lowest in vaginal and neutro­ penic patients. The study has also noted lowest MIC50 for non-albicans species C. glabrata. Since, fluconazole resistances have emerged, luliconazole is found to be a useful drug against Candida. Fluconazole are not active against non-albicans species, in that case lulicona­zole can be used. Thus the study has high­lighted the antifungal activity of lulicona­zole against Candida species. Further studies are needed regarding the in vivo activity.

Key Messages €€ Luliconazole has antifungal activity against Candida from different sources €€ Luliconazole is found to be effective against non-albicans species.

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ARTICLE 20

In vitro Additive Effect on Griseofulvin and Terbinafine Combinations Against Multidrug-resistant Dermatophytes Lana AJD, Pippi B, Carvalho AR, et al. In Vitro additive effect on griseofulvin and terbinafine combinations against multidrug-resistant dermatophytes.

Braz J Pharm Sci. 2018;54(2):e17149.

Abstract Antifungals such as terbinafine and griseofulvin are widely used to treat dermatophytic infections. In the current era, both drugs when used alone had developed drug resistance. The study has evaluated the in vitro synergistic effect of terbinafine and griseofulvin. New combination of terbinafine and griseofulvin can be used in dermatophytic infections.

COMMENT Dermatophytes are treated with wide range of antifungals. Most of the antifungals had developed resistance. Terbinafine and griseofulvin are the two commonly used anti­ fungals but in the current practice both when used separately had developed resistance. The present study has worked on the in vitro synergistic effect of terbinafine and griseofulvin in multidrug-resistance isolates. terbinafine and griseofulvin acts at different level on the fungal pathway. Terbinafine acts on ergosterol synthesis by inhibiting the enzyme 14α-demethylase. Griseofulvin inhibits the microtubule formation and hence the fungal cell wall synthesis. The different fungal strains that were used for the study are Trichophyton mentagrophytes, T. rubrum, Microsporum

gypseum and Microsporum canis. The antifungal susceptibility was done using checker board method. Minimum inhibitory concentration of both terbinafine and griseofulvin were calculated. Cell injury assay of both the drugs were calculated. Cell injury was maximum when both drugs were used in combination. The strains which were resistant to terbinafine and griseofulvin separately were found to be effective when both drugs used combinedly. Thus, the study highlighted that two drugs namely terbinafine and griseofulvin had a synergistic action in multidrug-resistant strains. In drug-resistant dermatophyte infections combination therapy can be given. Since the study has done in vitro, further studies are needed for in vivo analysis.

Key Messages €€ In the current era, combination therapy is a new treatment approach for dermatophytes €€ Terbinafine and griseofulvin are found to have synergistic action in multidrug-resistant cases.

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66 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 21

Traditionally Practiced Medicinal Plant Extracts Inhibit the Ergosterol Biosynthesis of Clinically Isolated Dermatophytic Pathogens Chellappandian M, Saravanan M, Pandikumar P, et al. Traditionally practiced medicinal plant extracts inhibit the ergosterol biosynthesis of clinically isolated dermatophytic pathogens.

J Mycol Med. 2018;28(1):143-9.

Abstract Certain medicinal plants have antidermatophytic activity. The study evaluated the minimum fungal concentration of ten medicinal plant extracts. Phyllanthus reticulatus showed best antifungal activity against T. rubrum and M. pachydermatis by inhibiting ergosterol synthesis. Plant extracts can be used in antifungal preparation in the near future.

COMMENT In the last decade, because of emerging antifungal resistance, pharmaceutical com­ panies have started showing interest in traditional medicines. The medicinal plants like Acalypha indica, Senna alata, Wrightia tinctoria, Senna auriculata, Acacia sinuata and phyla nodiflora that can be used in dermato­ logical disorders in Virudhunagar districts. The study describes the antidermato­ phytic property of about eighteen medicinal plants in South India. Among which Phyllanthus reticulatus  has an excellent antidermatophytic property against T. rubrum and T. mentagrophytes isolates. Bark, leaf and root of Phyllanthus reticulatus have a good medicinal value. In Europe the dried up leaves powder has been used to treat veneral sores.

Minimum inhibitory concentration and minimum fungal concentrations of all plant extracts were calculated. The controls used were ketoconazole and amphotericin  B. The effect of plant extracts on fungal cell wall ergosterol synthesis calculated. Phyllanthus  reticulatus  showed an effective inhibition of ergosterol synthesis. The study insists the use of herbal prepara­ tions to treat fungal infections in those patients who were in need of herbal medications. More long term in vivo studies are needed to assess the long term side effects and effectiveness and interactions with other products. In the near future, Phyllanthus reticulatus can be considered for its very good antifungal activity by inhibiting ergosterol synthesis.

Key Messages €€ Phyllanthus reticulatus showed best antifungal activity against T. rubrum and M. pachydermatis by

inhibiting ergosterol synthesis €€ To combat, antifungal resistance, herbal medicines can be tried as antifungals.

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ARTICLE 22

A Novel Antibiotic-like Substance Isolation from Dermatophyte, Trichophyton rubrum Aubaid AH, Al-Shawi, Haider A, et al. A novel antibiotic-like substance isolation from a dermatophyte, Trichophyton rubrum.

Reviews in Medical Microbiology. 2018;29(2):89-100.

Abstract The study isolated Trichophyton rubrum culture extract and tested its antibacterial and antioxidant property. Secondary metabolites from Trichophyton rubrum found to contain sulfones, kojic acid, fusidic acid and amides. The study reveals the antibiotic property of Trichophyton rubrum is by sulfones.

COMMENT Trichophyton rubrum is an important fungi that produce many anti bacterial metabolites. The study isolated Trichophyton rubrum culture extract and tested its antibacterial and antioxidant property. Similar study results were described by Peck et al. The culture mediums used for secondary metabolites production from Trichophyton rubrum are keratinized skin dextrosemodified liquid medium and Horse Hair dextrose liquid medium. Thin layer chromatography was used to isolate active compounds from crude extract. The organic groups in the active compound are characterized by infrared spectrophotometer analysis.

Brine shrimp lethality bioassay was used to assess the cytotoxic effect of secondary meta­ bolites. Cytotoxic effect is found to be directly proportional to concentration of the extracts. Acetone extracts from secondary metabolites found to contain potent antioxidant property. Secondary metabolites from Trichophyton rubrum found to contain sulfones, kojic acid, fusidic acid and amides. The study was the first to show presence of fusidic acid metabolites from Trichophyton rubrum. The study highlights antibacterial property particularly sulfones from secondary meta­ bolites of Trichophyton rubrum. In future, this secondary metabolites can be used in antibiotic production.

Key Messages €€ Secondary metabolites from Trichophyton rubrum found to contain sulfones, kojic acid, fusidic acid

and amides €€ Antibacterial and antioxidant property are isolated from secondary metabolites of T. rubrum.

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68 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 23

Caffeic Acid and Licochalcone a Interfere with the Glyoxylate Cycle of Trichophyton rubrum Cantelli BAM, Bitencourt TA, Komoto TT, et al. Caffeic acid and licochalcone A interfere with the glyoxylate cycle of Trichophyton rubrum.

Biomed Pharmacother. 2017;96:1389-94.

Abstract The most common superficial fungal infection dermatophytosis is caused by Trichophyton rubrum. Because of some similarity between mammalian cells and fungal cells many different antifungal preparations are lacking. The study determines the antifungal activity of two molecules namely caffeic acid and licochalcone A which hamper the glyoxylate cycle of T. rubrum.

COMMENT Dermatophytic infections have been increased worldwide in the recent past. T.  rubrum is the common etiological agent. Due to some similarity between mammalian cells and fungal cells many different antifungal preparations are lacking. The antifungal preparations in the market mostly have same mechanism of action. This study differs by focusing on two different molecules namely caffeic acid and licochalcone A that hamper the glyoxylate cycle of T. rubrum. Glyoxylate cycle is responsible for adaptation of fungal cell in the mammalian cell. Activation of this glyoxylate cycle helps in the survival of fungus.

Caffeic acid and licochalcone A exhibit antifungal activity by interfering with ergosterol synthesis and glyoxylate cycle. Minimum inhibitory concentrations of two molecules were recorded. The genes coding for ergosterol synthesis in T. rubrum was found to be repressed when co cultured with caffeic acid and licochalcone A. The enzyme namely iso citrate lyase in glyoxylate was found to be reduced by the two molecules. Thus anti­ fungal activity of caffeic acid and lico­chalcone A is by hampering glyoxylate pathway. Caffeic acid and licochalcone A can be used for antifungal preparations. Studies are required to analyze the effectiveness and side effect in humans.

Key Messages €€ Most antifungal preparations in the market have same mechanism of action €€ Caffeic acid and licochalcone A that hamper the glyoxylate cycle of T. rubrum.

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ARTICLE 24

Efficiency of Newly Prepared Thiazole Derivatives Against Some Cutaneous Fungi Ouf SA, Gomha SM, Eweis M, et al. Efficiency of newly prepared thiazole derivatives against some cutaneous fungi.

Bioorg Med Chem. 2018;26(12):3287-95.

Abstract The study analyzes the antifungal activity of some thiazole derivatives like arylazothiazole and arylhydrazothiazole. The antifungal activity has mainly due to side-chain aromatic compound. The antifungal activity was compared to fluconazole. Thiazole 7c and 11a have good keratinase activity and inhibit ergosterol synthesis.

COMMENT Dermatophytosis has become a major global burden. Because of in appropriate uses, treatment failures have been flourished. This study analyzes the antifungal activity of some fourteen thiazole derivatives like arylazothiazole and arylhydrazothiazole. The antifungal activity is mainly on the side chain compounds. When both chains are aromatic, antifungal activity is more compared to one aliphatic and one aromatic or nitro or chloro groups. Thiazole derivatives like 7a, 7c, 7e, 7f, 7 g, 7i, 7m and 11a have well antifungal activity compare to fluconazole.

The antifungal activity is by inhibiting ergosterol synthesis and keratinase activity. The antifungal activity was tested against Candida albicans, Trichophyton mentagrophytes and Microsporum gypseum. Minimum inhibitory concentration and Minimum fungal concentration of thiazole derivatives were recorded. Thiazole 7c and 11a have good keratinase activity and inhibit ergosterol synthesis. The antifungal activity was tested in guinea pigs. Thus, thiazole derivatives 7c and 11 a have antifungal action and further human studies are needed.

Key Message €€ Thiazole

7c and 11a have well antifungal action by keratinase activity and inhibiting ergosterol synthesis.

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70 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 25

Management of Dermatophytosis of Nail and Hair Singal A, Kayarkatte MN. Management of dermatophytosis of nail and hair.

Clin Dermatol Rev. 2017;1:30-3.

Abstract It is a review article about the management of common fungal infections of hair and nail namely tinea capitis and onychomycosis. The article analyzes the various treatment modalities such as topical, systemic, surgical and laser therapy.

COMMENT Tinea capitis and onychomycosis are the common dermatophytic infections in the world. This is a review article describing the management of tinea capitis and onychomycosis. The investigations that can be done are KOH direct microscopy, fungal culture, histopathology with PAS stain, dermoscopy and immunofluorescence micro­scopy. The available treatment options are topical, systemic, surgical and laser therapy. The topical therapies in onychomycosis are recommended for few situations like less than 30 % nail plate involvement, superficial white onychomycosis and as prophylaxis in recurrent onychomycosis. The topical drugs available are ciclopirox, amorolfine and efinaconazole. The newer US FDA approved drug is tavaborole 5% lotion for toe nail onychomycosis. The systemic therapy for onychomycosis is indicated when more than 30% nail plate involvement, nail matrix involvement and topical therapy is ineffective. The list of oral antifungals are griseofulvin, fluconazole, itraconazole and terbinafine. The side effects noted are headache/photosensitivity, abnormal liver enzymes and TEN of

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griseofulvin, itraconazole and terbinafine respectively. Surgical therapy alone is not effective. For better results surgery should be combined with medical therapy. The indications of surgery are dermatophytoma. Partial nail avulsion can be done. Multiple studies have stated NdYAG laser has a supplement modality. The investigations that can be done for diagnosis of tinea capitis are woods lamp, KOH microscopy, culture and trichoscopy. The list of oral antifungals used in tinea capitis are griseofulvin, fluconazole, itraconazole and terbinafine. Kerion requires saline compresses, topical antibiotics and topical steroids if severe inflammation is present. Topical antifungals alone are not effective for tinea capitis. This review article has covered the wide range of management options for common fungal infections namely tinea capitis and onychomycosis. It is a useful article for budding dermatologist as it has covered the adverse effects and treatment duration of each drug. The article could have elaborated more on surgical and laser therapy.

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Key Message €€ Multiple

treatment options are available for tinea capitis and onychomycosis and it should be selected for each individual need.

ARTICLE 26

Challenges and Opportunities in the Management of Onychomycosis Christenson JK, Peterson GM, Naunton M, et al. Challenges and Opportunities in the Management of Onychomycosis.

J Fungi. 2018;4(3):87.

Abstract Onychomycosis is a progressively increasing dermatophytic infection of the nail plate. The nail disorder is often difficult to treat because of fungi getting deep seated in the nail plate, recurrent infections, treatment for longer duration and poor patient compliance. The current available systemic and topical therapy for onychomycosis are not that much efficacious. This leads to the search of newer effective treatment approach. Combination treatment, physical therapies and natural treatment yield a good potential though many studies are lacking. Further studies are warranted in their new treatment plans.

COMMENT Onychomycosis accounts for 50% of all nail disorders. As all fungal infection, onycho­ m ycosis are contagious. The topical antifungals used are ciclopirox and amorolfine. The efficacy of topical antifungal is less because of poor penetration. The newer drugs are efinaconazole and 5% tavaborole. Further studies are required for the efficacy and adverse effect of these newer drugs. Oral antifungals available are fluconazole, terbinafine and itraconazole. They are used in almost all onychomycosis because of better penetrability compared to the topical

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treatment. Onychomycosis is often difficult to treat because of fungi getting deep seated in the nail plate, recurrent infections, treatment for longer duration and poor patient compliance. The average disease duration is as long as 18 years. Footwear surrounding the nail infection is responsible for longer period of disease. Recent data states that biofilms are produced by fungi and it is responsible for the recurrent infections and treatment failure. This leads to the search of newer effective treatment approaches like combination

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72 Year Book of Dermatology – 2019 Fungal Infections treatment, physical therapies and natural treatment. Natural treatments tried are Ageratina pichinchensis lacquer and Natural Coniferous Resin (NCR) lacquer. But the studies are in preliminary level and human-based trials are needed. Physical treatments available are laser, photodynamic treatment and plasma therapy. Laser provides antifungal activity by selective photothermolysis. Lasers that can be tried for onychomycosis are Nd:YAG, Er:YAG and fractional CO2 lasers. Cost is a major limitation factor for lasers.

Photodynamic therapy requires frequent clinical visit this may lead to poor compliance and treatment failure. Another physical treatment in trial is plasma therapy that by non thermal plasma provides antifungal activity. The advantage is no drug interactions and can be used in patient with other comorbidites. Combination therapies are systemic and topical given together as synergistic antifungal action. Other newer combination under trial are topical and iontophoresis and laser and systemic treatment. Much more human-based trials are needed for these new treatment modalities for onychomycosis.

Key Messages €€ Combination treatment, physical therapies and natural treatment yield a good treatment option for

onychomycosis

€€ More human-based trials are needed for these newer treatment modalities.

ARTICLE 27

In vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates Rezaei-Matehkolaei A, Khodavaisy S, Alshahni MM, et al. In vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates.

Antimicrob Agents Chemother. 2018;62(5):e02423-17.

Abstract The study compares the in vitro activity of efinaconazole with five other antifungal namely itraconazole, lanoconazole, fluconazole, luliconazole and terbinafine. The minimum inhibitory concentration was lowest for luliconazole, lanoconazole, efinaconazole, terbinafine, itraconazole and fluconazole in this order. The promising antifungals for T. rubrum and T. interdigitale are efinaconazole, lanoconazole and luliconazole.

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COMMENT Because of the emerging drug resistance newer antifungals are launched in the market for various dermatophytosis and onychomycosis. The study evaluates the in vitro efficacy of six antifungals namely efinaconazole, itraconazole, lanoconazole, fluconazole, luliconazole and terbinafine against T. rubrum and T. interdigitale. Minimum inhibitory concentrations of the six antifungals are recorded. Highest MIC is recorded for fluconazole. Three antifungals efinaconazole, luliconazole and lanoconazole have milder variation in MIC with no statistical significance.

The study found out that effectiveness of efinaconazole against Trichophyton isolates was same for people in Iran, America and Japan. Hence no geographical differences in the antifungal activity of efinaconazole are recorded. Efinaconazole showed less drug resistance compared to terbinafine. Low binding capacity of efinaconazole to nail keratin makes it a promising antifungal for onychomycosis. Thus study states that efinaconazole is least comparable to the current treatment options available for onychomycosis. In vivo studies are needed to analyze the effectiveness of efinaconazole.

Key Messages €€ The

promising antifungals for T. rubrum and T. interdigitale are efinaconazole, lanoconazole and luliconazole €€ Low binding capacity of efinaconazole to nail keratin makes it a promising antifungal for onychomycosis.

ARTICLE 28

Pediatric Onychomycosis: The Emerging Role of Topical Therapy Eichenfield LF, Friedlander SF. Pediatric onychomycosis: the emerging role of topical therapy.

J Drugs Dermatol. 2017;16(2):105-9.

Abstract Though thought to be rare previously fungal nail infections are now emerging as common nail plate infections in pediatric age group. It is a review article focusing on course and treatment of pediatric onychomycosis. Further studies are needed to work on the topical treatment of pediatric onychomycosis.

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74 Year Book of Dermatology – 2019 Fungal Infections COMMENT Onychomycosis are thought to be rare in pediatric age group in the past. However, now fungal nail infections are emerging in the pediatric age group. They are difficult to diagnose as most nail disorders mimic each other in infants and children. Onychomycosis can lead to discomfort, cosmetic disfigure­ ment, secondary infection, important health risk in immunocompromised or diabetics. The study reviewed the predisposing factors, reason for low incidence in children and prevalence of pediatric onychomycosis. All cases of childhood onychomycosis should be ruled out for tinea pedis. It is must to screen

the entire family for onychomycosis and tinea pedis. As recurrences are more common in pediatric age group, the treatment is very challenging and long-term systemic anti­ fungals are required. However, hesitancy of prolonged oral therapy for children and thinner and fast growing nails theoretically make them ideal candidate for topical therapy. The data regarding topical antifungal therapy in pediatric onychomycosis are very meager. Newer topical antifungals are available in the market. More research are needed in this field.

Key Message €€ As recurrences are more common in pediatric age group, the treatment is very challenging and long-

term antifungals are required.

ARTICLE 29

Tacrolimus, not Triamcinolone Acetonide, Interacts Synergistically with Itraconazole, Terbinafine, Bifonazole, and Amorolfine against Clinical Dermatophyte Isolates Zhang J, Tan J, Yang L, et al. Tacrolimus, not triamcinolone acetonide, interacts synergistically with itraconazole, terbinafine, bifonazole, and amorolfine against clinical dermatophyte isolates.

J Mycol Med. 2018;28(4):612-6.

Abstract This is a research article that compares the in vitro interactions of tacrolimus/triamcinolone acetonide with antifungals namely terbinafine, itraconazole, bifonazole and amorolfine using micro­ dilution method. Both tacrolimus/triamcinolone acetonide does not exhibit separate antifungal activity. Tacrolimus showed a synergistic activity with antifungals. Both drugs do not show any antagonism with antifungals.

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75

COMMENT This is a research article that compares the in vitro interactions of tacrolimus/ triamcinolone acetonide with antifungals namely terbinafine, itraconazole, bifonazole and amorolfine. The test strains used are T.  rubrum, T. mentagrophytes, E. floccosum and M. canis. The drug interactions are tested using microdilution checkerboard technique. Even in highest concentrations both tacrolimus/triamcinolone acetonide does not show any separate antifungal activity. However tacrolimus showed a very good synergistic action with itraconazole, bifonazole and terbinafine against Trichophyton strains.

Triamcinolone acetonide showed a weaker synergistic action with Itraconazole and Bifonazole for same Trichophyton strains. No synergistic actions are shown by triamcinolone acetonide with antifungals for E. floccosum and M. canis strains. Both drugs do not show any antagonism with antifungals. The article concludes that tacrolimus showed a good synergistic action with antifungals particularly terbinafine and bifonazole for dermatophyte isolates. Whenever needed tacrolimus can be given along with antifungals compared to triamcinolone acetonide.

Key Message €€ Tacrolimus showed a good synergistic action with antifungals particularly terbinafine and bifonazole

for dermatophyte isolates.

ARTICLE 30

Efficacy and Tolerability of Amorolfine 5% Nail Lacquer in Combination with Systemic Antifungal Agents for Onychomycosis: A Meta-analysis and Systematic Review Feng X, Xiong X, Ran Y. Efficacy and tolerability of amorolfine 5% nail lacquer in combination with systemic antifungal agents for onychomycosis: A meta-analysis and systematic review.

Dermatol Ther. 2017;30(3).

Abstract This is a review article that analyzes the safety and efficacy of amorolfine 5% nail lacquer in onychomycosis with other systemic antifungals. The combination therapy is more effective than monotherapy of oral antifungals.

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76 Year Book of Dermatology – 2019 Fungal Infections COMMENT Onychomycosis are difficult to treat com­ pared to other superficial fungal infections. Onychomycosis required pro­longed treat­ ment. Most often pulse therapy with oral anti­ fungals given. However no complete clearance is achieved. This is a review article that analyzes the safety and efficacy of amorolfine 5% nail lacquer in onychomycosis with other systemic antifungals. Amorolfine is a topical antifungal that acts by reducing the ergosterol synthesis

by inhibiting 14 delta sterol reductase and 14 cholesterol isomerase. Amorolfine 5% nail lacquer is given once or twice weekly along with oral antifungals. The combination therapy in onycho­ mycosis showed a higher level of complete clearance compared to oral antifungals alone. There is no significant adverse effect for 5% amorolfine nail lacquer. The only factor to be considered is cost of nail lacquer.

Key Message €€ The combination therapy in onychomycosis showed a higher level of complete clearance compared

to oral antifungals alone.

ARTICLE 31

Promising Antifungal Activity of Croton tricolor Stem Essential Oil Against Candida yeasts Miranda FM, Nascimento Junior B, Aguiar RM, et al. Promising antifungal activity of Croton tricolor stem essential oil against Candida yeasts.

J Essen Oil Res. 2018;2:1-5.

Abstract The article evaluates the antifungal activity of essential oil derived from stems of Croton tricolor against various Candida yeasts. Minimum inhibitory concentration was obtained by microdilution method.

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77

COMMENT This original article characterizes the antifungal activity of essential oil derived from stems of Croton tricolor against various Candida yeasts. With the help of Clevenger apparatus by hydrodistillation technique essential oils are extracted from the stems of croton tricolor. Epiglobulol, α-trans-bergamotol α-bis­ abolol and β-caryophyllene are the four major components present in essential oils from stems of Croton tricolor. Minimum inhi­ bitory concentration of essential oil for each Candida strains are evaluated by microbiological assays by micro dilution

method. Essential oil concentrations ranging from 1.0 to 1024 μg/mL inhibit the growth of all tested Candida strains. This study proves without doubt that essential oil derived from stems of Croton tricolor has siginificant antifungal activity against Candida species. Essential oil derived from stems of Croton tricolor is natural product with excellent antifungal activity that can be used in the treatment of candidiasis. More studies are needed to find the efficacy and interactions of essential oil derived from stems of Croton tricolor in human.

Key Message €€ Essential oil derived from stems of Croton tricolor is natural product with excellent antifungal activity

that can be used in the treatment of candidiasis.

ARTICLE 32

Diffuse Dermatophytosis Occurring on Dimethyl Fumarate Therapy Greenstein JI. Diffuse dermatophytosis occurring on dimethyl fumarate therapy.

Mult Scler. 2018;24(7):999-1001.

Abstract The article evaluates the adverse events occurring after dimethyl fumarate therapy with special reference to diffuse dermatophytosis. Lymphocyte counts were recorded. Complete dermatological examinations were made. Diffuse dermatophytosis widens the list of opportunistic infections that occurs after dimethyl fumarate therapy.

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78 Year Book of Dermatology – 2019 Fungal Infections COMMENT Dimethyl fumarate therapy is known to cause wide array of opportunistic infections. This is accounted by its known side effect lymphopenia. This article evaluates the adverse effects of dimethyl fumarate particularly diffuse dermatophytosis. Clinical course and complete dermatological exami­ nations were done. Lymphocyte counts were noted.

Other causes of immunosuppression and lymphopenia were ruled out. Thus it was found out that diffuse dermatophytosis is due to dimethyl fumarate therapy. Among the opportunistic infections caused by dimethyl fumarate diffuse dermatophytosis is added to the list. More studies are needed to find the exact mechanism of action for lymphopenia and immunosuppression after dimethyl fumarate therapy.

Key Messages €€ Dimethyl fumarate therapy is known to cause wide array of opportunistic infections €€ Diffuse dermatophytosis is added to the list.

ARTICLE 33

In vivo Antifungal Activity of Dipyrithione Against Trichophyton rubrum on Guinea Pig Dermatophytosis Models Song X, Wei YX, Lai KM, et al. In vivo antifungal activity of dipyrithione against Trichophyton rubrum on guinea pig dermatophytosis models.

Biomed Pharmacother. 2018;108:558-64.

Abstract Dermatophytosis has become a global health problem. Besides a wide range of antifungals available in the market, search of new antifungal still exist because of drug resistance. This article describes the in vivo antifungal activity of dipyrithione against the most common etiological agent of dermatophytosis Trichophyton rubrum in guinea pig models.

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79

COMMENT Despite wide list of antifungals starting from griseofulvin to echinocandins, search of newer antifungal still exist. This is because of drug resistance to these antifungals. This study describes the in vivo antifungal activity of dipyrithione against the most common etiological organism of dermatophytosis Trichophyton rubrum in guinea pig models. Dipyrithione is a natural plant compound with broad spectrum antimicrobial activities. Thus it is a potential candidate with antifungal property. MIC50 value of miconazole and dipyrithione against T. rubrum was compared. MIC50 of miconazole was 1.38 μM

and MIC50 of dipyrithione was found to be 6.03 μM. This proves the antifungal property of dipyrithione. Dipyrithione also showed an additional feature of morphological changes in T. rubrum which can be measured by morphological interference assay. The study has noted healing effect in guinea pig models infected with T. rubrum. The study has clearly described the in vitro and in vivo antifungal activity of dipyrithione against T. rubrum. Dipyrithione can be labeled as novel antifungal agent. However, human studies are needed to study the safety profile of dipyrithione.

Key Messages €€ Dipyrithione

has a potent in vivo and in vitro antifungal activity against Trichophyton rubrum in guinea pig models €€ Dipyrithione can be labeled as novel antifungal agent.

ARTICLE 34

Antifungal Therapeutic Failures in India: An Important Issue being Overlooked Sonthalia S, Agrawal M, Goldust M, et al. Antifungal therapeutic failures in India: an important issue being overlooked.

Lancet Infect Dis. 2018;18(11):1181-2.

Abstract Dermatophytosis treatment had become a challenge nowadays because of emerging antifungal therapeutic failures. Due to topical steroids misuse treatment of refractory dermatophytosis has become a nightmare. Another contributing factor is primary care physicians treating skin disorders. Continued medical educations are required for other physicians regarding the avoidance of steroids and prevention of antifungal failures.

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80 Year Book of Dermatology – 2019 Fungal Infections COMMENT Refractory dermatophytosis is increased in the recent past in India. Antifungal therapy failures are escalating. The important contributing factor is misuse of topical steroid in dermatophytosis. Another important issue that should be considered is other primary care physicians treating dermatophytosis. In India, most of the times people visit primary care physicians or general practitioners for first consultation including cutaneous conditions. This scenario is even more common in rural areas as most of the dermatologists are in urban areas. The primary care physicians are offering suboptimal treatment to various dermatoses particularly fungal infections. Two important factors contribute to this, first being less training during undergraduate period and the second reason being because of heavy patient load these general practitioners have less time to update their knowledge to particular dermatoses. Mostly other specialty doctors refer dermatoses like psoriasis, erythroderma,

bullous disorders, eczema and severe infections. But they are not referring fungal cases and treating on their own suboptimally. Even some dermatologist use topical steroid-based antifungals for treating fungal infections. The standard of dermatology in the undergraduate training period has to be improved for the better equipment as future physicians. Treatment guidelines for fungal infec­ tions can be made so that it can be used by general physicians who treat loads of dermatophytosis cases. It is believed that many dermatologist have a strong inclination to discourage general physician acquiring knowledge to treat dermatoses is counterproductive. National level continued medical educations are required for other physicians regarding the avoidance of steroids, proper treatment regarding fungal infections and prevention of antifungal failures. It should be implemented as soon as possible to avoid the epidemic of refractory dermatophytosis.

Key Messages €€ Dermatophytosis

treatment had become a challenge nowadays because of emerging antifungal therapeutic failures €€ National level continued medical educations are required regarding the avoidance of steroids, proper treatment regarding fungal infections and prevention of antifungal failures.

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81

ARTICLE 35

Utilization of Lichen Metabolites as Natural Antifungal Drug against Dermatophytosis Upret DK. Utilization of lichen metabolites as natural antifungal drug against dermatophytosis.

J Res Opin. 2018;1(1).

Abstract Dermatophytosis treatment has become a great task because of treatment resistance and failure. This results in search of newer antifungal each day. This study describes the antifungal property of lichen metabolites and their use against dermatophytosis.

COMMENT Dermatophytosis has increased in the past two decades. Treatment has become a difficult task because of antifungal resistance. Each person in the family acquires dermato­ phytosis from one another and cost factor is a big burden. This study assesses the antifungal property of lichen metabolites and their use against dermatophytosis. Shahi et al. has found out that the aqueous extract of lichens such as Peltigera praetextata had antifungal activity against different fungal species such as T. rubrum, T. tonsurans, T. violaceum, T.  mentagrophytes, M. canis, M. gypseum, M. audouinii, M. nanum and E. floccosum. The study described that Peltigera praetextata has fungistatic activity at 40 µL/mL and fungicidal at 60 µL/mL against pathogenic fungal species. It was noted that even for 2 years, the potential of the inoculums at heavy doses of minimum fungicidal concentrations had not expired.

No adverse events are seen in the human skin for up to 10% concentration. The study prepared an ointment formu­ lation made of aqueous extract of Peltigera praetextata. The study population includes mycologically proven tinea cruris, tinea pedis or tinea corporis cases. The total sample size was 30. All patients were given treatment for 3 weeks with the newly prepared ointment formulation made of aqueous extract of Peltigera praetextata or twice daily application. At the end of three weeks, complete cure were seen in 35% and significant improvement in 40%. After 2 months, no relapses were recorded on KOH examination. The ointment was cost effective, so that even all family members can afford at a same time. The ointment had no significant adverse effects. Thus lichen metabolites could be used as an antifungal agent in the near future.

Key Message €€ Lichen metabolites namely Peltigera praetextata has fungistatic activity at 40 µL/mL and fungicidal

at 60 µL/mL against pathogenic fungal species.

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82 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 36

Investigation of Ethyl Cellulose Microsponge Gel for Topical Delivery of Eberconazole Nitrate for Fungal Therapy Bothiraja C, Gholap AD, Shaikh KS, et al. Investigation of ethyl cellulose microsponge gel for topical delivery of eberconazole nitrate for fungal therapy.

Ther Deliv. 2014;5(7):781-94.

Abstract The study evaluates the ethyl cellulose microsponge gel used for topical delivery of eberconazole nitrate cream. Microsponge gel helps in the control release of the drug and four times higher retention of the drug in the upper layers of the skin. Ethyl cellulose microsponge can be used as a potential topical carrier of eberconazole nitrate in antifungal treatment.

COMMENT Eberconazole are currently used in the treatment of dermatophytosis. The study evaluates the ethyl cellulose microsponge gel used for topical delivery of eberconazole nitrate cream. The quasiemulsion solvent diffusion method was used to prepare ethyl cellulose microsponge. The physical characteristics of micro­ sponge-like drug—polymer ratio, amount of emulsifier, internal phase volume, stirring speed and stirring time were analyzed. Hydrogel was used for dispersion of optimized microsponges. Porous and spherical micro­ sponges were collected. The particle size for

optimized microsponges was 24.5 µm. The drug content percentage was around 43%. The entrapment efficiency for optimized microsponges was 91%. The advantages of microsponge loaded gels are controlled release of the drug and complete nonirritant nature to rat skin. In vivo study had demonstrated four time higher retention of the drug in the upper layers of the skin compared to the commercial available cream. The study concludes that ethyl cellulose microsponge can be used as a potential topical carrier of eberconazole nitrate in antifungal treatment.

Key Message €€ The

controlled release, nonirritancy and higher retention of the drug makes ethyl cellulose microsponge a potential drug delivery system for eberconazole nitrate.

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83

ARTICLE 37

A Comparative Study of Efficacy and Safety of Eberconazole versus Terbinafine in Patients of Tinea Versicolor Sharma J, Kaushal J, Aggarwal K. A comparative study of efficacy and safety of eberconazole versus terbinafine in patients of tinea versicolor.

Indian J Dermatol 2018;63:53‐6.

Abstract Pityriasis versicolor is a superficial fungal infection caused by the fungus Malassezia furfur. The condition is usually asymptomatic and patients approach for treatment for the pigmentation. This study was conducted to compare the efficacy and safety of eberconazole and terbinafine in patients of pityriasis versicolor. The results showed that though both the drugs were effective, eberconazole showed better response and curative rate and no relapses during the follow-up period.

COMMENT The treatment for pityriasis versicolor (PV) is usually with topical agents and systemic drugs are used only when it is extensive and frequent relapses are present. The topical agents used commonly are the drugs belonging to the azole group of antifungals. This randomized controlled trial was conducted to determine the efficacy and safety of eberconazole with terbinafine in patients of PV. The efficacy of the above treatment

was assessed with clinical examination, KOH examination, wood’s lamp examination and safety assessment was also performed at the end of the treatment. The results showed that both the drugs were equally efficacious and both the drugs gave clinical and mycological cure but the response was quicker when eberconazole was used. Also no relapse was seen with patients treated with eberconazole.

Key Message €€ Eberconazole has the advantage of providing faster results and minimal/no relapse rate in this study.

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84 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 38

Antifungal Drug Susceptibility Profile of Clinically Important Dermatophytes and Determination of Point Mutations in Terbinafine-resistant Isolates Salehi Z, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Antifungal drug susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates.

Eur J Clin Microbiol Infect Dis. 2018;37(10):1841-6.

Abstract Antifungal susceptibility testing can effectively reduce the increasing drug-resistant dermato­ phytosis. The study evaluates the antifungal susceptibility of some clinically important fungal species and point mutations in terbinafine-resistant isolates.

COMMENT Drug-resistant dermatophytosis is increasing in the recent past. Antifungal susceptibility testing can effectively reduce the increasing drug-resistant dermatophytosis. The present study evaluates the antifungal susceptibility of some clinically important fungal species. The study also determines the point mutations in terbinafine-resistant isolates. Ninety seven cases of mycologically proven dermatophytosis were taken. Antifungal susceptibility test for four dermatophytic species such as T. rubrum, T. tonsurans, T. interdigitale and E. floccosum were asses­ sed. Minimum inhibitory concentration for

various antifungal luliconazole, terbinafine, griseofulvin, itraconazole, voriconazole, ketaconazole, lanoconazole and econazole were determined. The most susceptible organism to terbinafine was found to be Trichophyton tonsurans. E. flocossum was most resistant to terbinafine. Leu393Phe substitution mutation can cause terbinafine resistance at the rate of 2% for T. rubrum and T. tonsurans. The study emphasizes the importance of antifungal susceptibility test prior to starting treatment in order to avoid drug resistance.

Key Messages €€ Drug resistance can be avoided by proper prior antifungal susceptibility testing €€ E flocossum was most resistant to terbinafine.

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ARTICLE 39

The Role of Shoe and Sock Sanitization in the Management of Superficial Fungal Infections of the Feet Gupta AK, Versteeg SG. The role of shoe and sock sanitization in the management of superficial fungal infections of the feet.

J Am Podiatr Med Assoc. 2018.

Abstract Dermatophytic reinfections are common because of presence of fungal reservoirs such as infected shock, shoe or textiles. Effective sanitization can definitely prevent the dermatophytic reinfection. This review article analyzes the sanitization option given in 33 studies. Ozone application and UV radiation are newer effective method for shoe and sock sanitization.

COMMENT Relapse and recurrence rate range from 10 to 50% in superficial fungal infection especially onychomycosis. Shoe and sock trap the sweat and skin and acts as a fungal reservoir for dermatophytic infection. The review article analyzes the various saniti­zation options available for shoe and sock. Infected shoe acts as a reservoir for tinea pedis in 30% and 80% in onychomycosis. Multiple sanitization options such as formaldehyde fumigation, application of foot powder, ozone application and UV radiation to prevent the fungal reservoir. The basic sanitization option available is to soak it in boiled water but shoes will

get spoiled. Antimicrobial and antifungal impregnated shoes can effectively prevent the fungal reservoir. Formaldehyde fumigation is effective but not recommended nowadays because of formaldehyde dermatitis. Sanitization powders can give excellent results. Ozone application and UV radiation are newer effective method for shoe and sock sanitization. Knowledge gap about the newer techniques and cost factor prevent them providing effective sanitization. Effective sanitization can definitely cut off the fungal reservoir and prevent the reinfection. Future studies are needed for the modern sanitization techniques.

Key Messages €€ Ozone application and UV radiation are newer method for shoe and sock sanitization €€ Effective sanitization can definitely cutoff the fungal reservoir and prevent the reinfection.

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86 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 40

Eberconazole—Pharmacological and Clinical Review Moodahadu-Bangera LS, Martis J, Mittal R, et al. Eberconazole—Pharmacological and clinical review.

Indian J Dermatol Venereol Leprol. 2012;78:217-22.

Abstract The topical antifungal drugs used for the treatment of dermatophytosis are many belonging to the azole and other groups of antifungals. Eberconazole was introduced in the year 2005 for the treatment of cutaneous fungal infections. This article describes the pharmacology of eberconazole and the comparison of efficacy of eberconazole with other antifungal agents. It can be concluded that good efficacy, safety and tolerability of eberconazole makes it an attractive alternative in the treatment of superficial fungal infections.

COMMENT Eberconazole is a broad spectrum antifungal agent effective against dermatophytes, Candida and Malassezia yeasts. It also has activity against gram-positive bacteria. Eberconazole has fungicidal and fungistatic action based on the concentration. It inhibits ergosterol synthesis by inhibiting the enzyme 14 α-demethylase. There is reported antiinflammatory activity due to inhibition of lipoxygenase and cyclooxygenase pathway. Previous studies have shown that the minimal inhibitory concentrations of various antifungal topical agents with eberconazole revealed that it has the lowest MIC and has the benefit over other drugs. The plasma and urine levels of the drug after topical application with eberconazole is detectable very less. The efficacy of eberconazole has been compared with other drugs like clotrimazole and miconazole showed that the effect of this drug was comparable to that of miconazole.

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In the treatment of cutaneous mycosis eberconazole was found to be more effective than other drugs like clotrimazole. There was good clinical improvement after 2 weeks of therapy with mild side effects like burning sensation. The studies regarding safety of ebercona­ zole showed that the drug was not detectable in serum and urine indicating no systemic absorption. In phase 1 study, multiple appli­ cation of the drug produced mild burning sensation and dryness but no other major side effects and was well tolerated. In phase 2 study, erythema and pruritus was commonly seen. In a phase 3 study few subjects with candidiasis withdrew the drug due to local cutaneous irritation. The immediate reaction after application of the drug was coldness and later with increasing doses, itching was noted. The drug has been formulated in a cream base with ease of application with better absorption rate.

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Section 3: Management Studies The article shows that eberconazole is a safe, effective tolerable drug with lack of sensitising

87

properties making it a favorable option in the topical treatment of dermatophytosis.

Key Message €€ Good

efficacy, safety and tolerability of eberconazole makes it an attractive alternative in the treatment of superficial fungal infections.

ARTICLE 41

Propolis for the Treatment of Onychomycosis Veiga FF, Costa MI, Cótica ÉSK, et al. Propolis for the treatment of onychomycosis.

Indian J Dermatol. 2018;63(6):515-7.

Abstract Onychomycosis is often a major public health problem because of its contagious nature and fairly affect the quality of life. Long-term treatments with high cost are usually needed. This study evaluated the use of propolis extract for treatment of onychomycosis. Propolis extract showed a favorable response for onychomycosis.

COMMENT The fungal nail infection is termed as onychomycosis and it is often a major public health problem because of its contagious nature. The antifungal treatments available for onychomycosis are of high cost and with more adverse effects. This is responsible for poor compliance by the patient. Propolis extract proved to have significant effect in fungal infections. However in vivo studies on propolis extract are lacking. This study evaluated the use of propolis extract for treatment of onychomycosis. The study conducted on three elderly patients with onychomycosis. Four nails

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were taken from each patient. The study has found out that onychomycosis due to Fusarium and Candida are increasing. Onychomycosis are often associated with paronychia. Propolis extract’s composition is very complex. The important constituent is flavonoids and it has potent antifungal activity. Propolis extract have antibacterial, antifungal and anti-inflammatory property. Propolis extract have antioxidant effect and wound healing property. The study found out that out of four nails, two showed complete reduction and

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88 Year Book of Dermatology – 2019 Fungal Infections rest two showed fifty percent clearance of onychomycosis. Thus propolis extract can be used to treat onychomycosis cases since

propolis extract have a potent antifungal effect with no significant side effects and it is cost effective.

Key Messages

.

€€ Propolis extract have a potent antifungal effect with no significant side effects €€ Propolis extract can be an alternate for conventional antifungal agent.

ARTICLE 42

A Comparative Study of Quality of Life of Eberconazole versus Terbinafine in Patients of Tinea Versicolor Sharma et al. A comparative study of quality of life of eberconazole versus terbinafine in patients of tinea versicolor.

World Journal of Pharmacy and Pharmaceutical Sciences. 2017; 6(1): 1146-54.

Abstract This study is a randomized controlled trial to study the quality of life in patients with pityriasis versicolor with the drugs eberconazole and terbinafine. This study was conducted because pityriasis versicolor has effect on the pigmentation either hyper/hypopigmentation and this causes the main decrease in the quality of life leading to low self-esteem and embarrassment. The results of the study showed that there was not much statistical difference in the QOL score but in the social domain eberconazole had the better advantage over terbinafine.

COMMENT Pityriasis versicolor is a superficial fungal infection which causes no/minimal symptoms like itching to the patient. The other concern due to this disorder is the presence of hyper/ hypopigmentary changes associated with it. Also the pigmentary abnormalities do not respond immediately with treatment. This causes decrease in the quality of life of these patients.

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This study was conducted to determine the effects of the drugs eberconazole/terbinafine in the quality of life of patients with pityriasis versicolor. The patients were divided into two groups with each group given either eberconazole or terbinafine. The study groups applied the topical agents for 2 weeks and later they were followed after at 4 and 8 weeks. The QOL assessment

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Section 3: Management Studies was made with DLQI questionnaire in which emotional, physical and social domains were focussed. The results showed that both the drugs were equally efficacious and no statistical difference

89

was noted between the two drugs. But with regards to social domain, eberconazole showed statistically significant improvement and overall assessment showed eberconazole to have the upper hand over terbinafine.

Key Message €€ The results of the study showed that there was not much statistical difference in the QOL score but in

the social domain eberconazole had the better advantage over terbinafine.

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Section 4: Miscellaneous Studies ARTICLE 1

Tinea folliculorum Complicating Tinea of the Glabrous Skin: An Important yet Neglected Entity Sun PL, Lin YC, Wu YH, et al. Tinea folliculorum complicating tinea of the glabrous skin: an important yet neglected entity.

Med Mycol. 2018;56(5):521-30.

Abstract Dermatophytic infections affecting the glabrous skin termed as tinea corporis infects the skin primarily. A variant of tinea corporis termed Majocchi’s granuloma is a nodular granulomatous perifolliculitis seen in lower limbs. This article was conducted to determine whether the fungal infection of the glabrous skin involves the hair follicle surrounding the affected area. The results showed that with dermascopic examination of the affected region showed broken hair as black dots on the surface. This shows that tinea involvement of the glabrous skin can involve hair follicle also and therapy should be directed bearing this in mind.

COMMENT Dermatophytic infections are classified according to the site of involvement like tinea capitis and tinea barbae when it involves the hair bearing regions. The tinea infection of the glabrous skin is termed as tinea corporis. Tinea corporis may not be strictly limited to the glabrous skin and hair follicle involvement must be considered for the treatment duration may increase and only topical therapy might not be sufficient in treating such cases. This study was performed to determine the involvement of hair follicles in cases of tinea corporis. This was a clinico-mycological study

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which included patients of tinea corporis and hair follicular involvement was determined by the use of dermascopy when the findings of hair follicle involvement like broken hair in the form of black dots, curly hair were noted. Topical antifungals in addition to oral antifungals was given and all the patients responded well. This article emphasizes that the involvement of hair follicles in glabrous skin of tinea patients should be considered by proper examination as the treatment duration increases when the hair follicle involvement occurs and systemic antifungal therapy is required.

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Key Messages €€ The article emphasizes the fact that involvement of hair follicles can occur in cases of tinea infection

of the glabrous skin

€€ Dermascopic examination of hair follicle involvement are broken hair, black dots and curly hairs.

ARTICLE 2

Coexistence of Fungal Infections in Psoriatic Nails and their Correlation with Severity of Nail Psoriasis Chaowattanapanit S, Pattanaprichakul P, Leeyaphan C, et al. Coexistence of fungal infections in psoriatic nails and their correlation with severity of nail psoriasis.

Indian Dermatol Online J. 2018;9(5):314-7.

Abstract The nail involvement of psoriasis can be complicated by the concomitant fungal infection so the differentiation between the two becomes difficult. This study was performed to assess the prevalence of fungal infections in cases of nail psoriasis and to correlate with the disease severity. The results showed that there was a high rate of fungal infections in cases of nail psoriasis and belonged to the group of yeasts, non-dermatophytic fungi. Also the occurrence of fungal infection of the nail was seen more in severe cases of nail psoriasis.

COMMENT Nail involvement by psoriasis ranges from 20 to 70% of the cases and the differentiation between nail psoriasis and onychomycosis is difficult clinically. Also to confirm psoriasis of the nail, a nail biopsy is required which is quite painful and is not routinely performed. Also the confirmation of onychomycosis by direct microscopy and culture is not specific and also there is a delay in the growth of fungi in culture. Also the treatment of both the conditions is entirely different as systemic antifungals are

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the treatment for onychomycosis whereas intralesional steroids, methotrexate and other drugs are given for nail psoriasis. This study was performed to assess the prevalence of fungal infections in cases of nail psoriasis and to correlate with the disease severity. This is a retrospective study conducted in a tertiary care centre in Thailand. The cases were selected with the least and the most affected finger and toe nail involvement based on the NAPSI score and culture was the

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92 Year Book of Dermatology – 2019 Fungal Infections definite investigation performed to isolate the fungal species. Nail involvement was maximally affected in patients of chronic plaque type psoriasis. The fungal culture results showed that Candida was the common fungus affecting nails of psoriasis patients whereas dermatophytes were not detected in any of the psoriatic nails. The causative agents differed from the ones isolated from the fingers and toe nails.

Non-dermatophytes were the causative agents of onychomycosis of the toe nails in this study. The limitations of this study is that it is not a case-control study as healthy controls were not compared and also the inclusion criteria included old patients of psoriasis who took treatment previously that might cause discrepancies in the results obtained. More studies are required to support the findings seen in this study.

Key Messages €€ High rate of fungal infections was seen in cases of nail psoriasis and belonged to non-dermatophytic

fungi

€€ The occurrence of fungal infection of the nail was seen more in severe cases of nail psoriasis.

ARTICLE 3

A Novel Dermatophyte Relative, Nannizzia perplicata sp. nov., Isolated from a Case of Tinea Corporis in the United Kingdom Borman AM, Szekely A, Fraser M, et al. A novel dermatophyte relative, Nannizzia perplicata sp. nov., isolated from a case of tinea corporis in the United Kingdom.

Med Mycol. 2018.

Abstract This article describes the isolation of a new species of dermatophyte isolate from the tinea corporis lesion from a patient of lupus autoimmune syndrome. Initial examination of the scales showed features of dermatophytes and hence antifungal treatment was started. But the patient did not respond to the treatment for 5 months and the lesions were persisting and hence repeat KOH examination was done and smooth microconidia with unicellular aleuriospores which showed similarity with dermatophytes and a phylogenetic analysis of the same lead to the isolation of the new species Nannizzia perplicata.

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COMMENT The article reported the occurrence of a new species of dermatophyte Nannizzia perplicata which is a relative of Nannizzia nana. This is being reported as a rare isolate as dermatophytosis is usually caused by Epidermophyton, Trichophyton and Microsprorum species. The article describes a female patient in United Kingdom, a case of lupus autoimmune overlap syndrome on treatment with steroids and methotrexate. She had taken treatment for dermatophytosis previously and resolved with treatment. After 6 months she developed similar lesions for which direct microscopy and culture was performed and the results revealed fungal elements with unusual morphology distinctive from dermatophytes

and hence it was subjected to phylogenetic study. After molecular and phylogenetic analysis, a new dermatophyte relative Nannizzia perplicata was isolated in addition to N. gypsea complex. This is a geophilic organism and hence commonly affects the farmers and gardeners and hence occupational history is important. The same organism was isolated in Czech Republic isolated from leg lesion. The other sample examination from these taxa is required to assess strain variability within the species at both the molecular and morphological level and to determine whether the isolates of this species are resistant to terbinafine.

Key Messages €€ A new dermatophytic relative Nannizzia perplicata, a geophilic fungus isolated from a lesion of tinea

corporis

€€ This is a geophilic organism and hence commonly affects the farmers and gardeners.

ARTICLE 4

PRP8 Intein in Dermatophytes: Evolution and Species Identification Garcia Garces H, Cordeiro RT, Bagagli E, et al. PRP8 intein in dermatophytes: Evolution and species identification.

Med Mycol. 2018;56(6):746-58.

Abstract Dermatophytes are keratinophilic fungi which use keratin as carbon and nitrogen source and exhibit a saprophytic existence. Nuclear ribosomal techniques are used for the identification of species within the family. The search for newer, faster techniques to identify in one single

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94 Year Book of Dermatology – 2019 Fungal Infections step like PCR is gaining attention recently. The criteria are fulfilled by intein, a self-splicing genetic element. The study was performed to determine the usage of PRP8 intein to establish phylogenetic relation of the dermatophytes and species recognition. The results showed that PRP8 intein can be used as a powerful tool in the analysis and systematic classification of dematophytosis.

COMMENT This study was performed to evaluate the use of new, faster technique like PRP8 intein in the establishment of phylogenetic relationship of the dermatophytes and also for recognition of its species. This was undertaken because the techniques like nuclear ribosomal sequencing techniques for species identification are multistep processes and hence new techniques which require single step processing like PRP8 intein can be utilized. Inteins are the self-splicing genetic

elements which code the important part of spliceosome. The aim of this study is to determine the usage of PRP8 intein to establish the phylogenetic relation of the dermatophytes and for recognition of species. The results showed that the phylogenetic study results obtained with this technique was similar to that seen with other phylogenies proving that intein 8 can serve as a powerful tool in the analysis and phylogenetic classification of dematophytosis.

Key Message €€ Intein

8 can serve as a powerful tool in the analysis and phylogenetic classification of demato­ phytosis.

ARTICLE 5

In silico Characterization of Tandem Repeats in Trichophyton rubrum and Related Dermatophytes Provides New Insights into their Role in Pathogenesis Franco ME, Bitencourt TA, Marins M, et al. In silico characterization of tandem repeats in Trichophyton rubrum and related dermatophytes provides new insights into their role in pathogenesis.

Database (Oxford). 2017;2017:bax035.

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Abstract Trichyphyton rubrum is the common organism causing dermatophytosis worldwide. Genetic analysis of fungal genome has shown that the tandem repeats plays role in genetic variability and pathogenesis of the organism. This study was conducted to create a database on Dermatophyte Tandem Repeat Database (DTRDB) for the storage and identification of T. rubrum and six other species. The results showed that the created database can be used to determine the pathogenicity of the organisms and to discover new antifungal agents.

COMMENT Trichophyton rubrum is an anthropophilic dermatophyte which is the commonest organism causing dermatophytosis. The clinical importance of this organism is that it causes invasive fungal infections in immunocompromised patients along with six other species. Genetic analysis has shown that tandem repeats play a role in genetic variability and pathogenesis of the organism. These data are important because the virulence and other habits of the fungal species can be determined by this. Tandem repeats are the hypervariable genetic sequences playing a role in regulating gene expression and pathogenicity. These genetic sequences are present in fungal proteins involved in cell adhesion responsible

for the fungal infection to develop and progress. The present study was conducted to identify these tandem repeats and create a database on DTRDB for the storage and identification of T. rubrum and six other species. The data collected from this database can be used for the different function each repeat has in the pathogenicity as well as other factors involving pathogen-host interaction. The search from this database reveals that the repeats occur in 20–30% of the genes which can help in aiding the organism to establish infection by creating a favorable environment. The above data can be used for the discovery of new antifungal agents.

Key Messages €€ Genetic analysis has shown that the tandem repeats plays role in genetic variability and pathogenesis

of the organism

€€ The above data can be used for the discovery of new antifungal agents.

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96 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 6

The Frequency, Antifungal Susceptibility and Enzymatic Profiles of Candida Species in Cases of Onychomycosis Infection Sav H, Baris A, Turan D. The frequency, antifungal susceptibility and enzymatic profiles of Candida species in cases of onychomycosis infection.

Microb Pathog. 2018;116:257-62.

Abstract Onychomycosis due to Candida species is commonly encountered but little data are available regarding the epidemiology, pathogenesis and antifungal susceptibility of this organism. Hence this study was conducted to determine the epidemiology, pathogenesis and susceptibility to azole antifungals in patients residing in continental climates. The samples from cases of onychomycosis were cultured and the isolates were isolated for species identification and susceptibility to antifungal agents was studied. The results showed that the common identified species was C. parapsilosis and the effective antifungal agents were ketoconazole and voriconazole.

COMMENT The number of studies regarding the epidemiology and antifungal susceptibility of Candida species is very less and hence this study was performed to assess the same. The antifungal susceptibility to azole derivatives was studied. The samples from the patients with onychomycosis were subjected to fungal culture technique and later the species identification was done and also the antifungal susceptibility and biofilm forming capacity of the Candida species was studied.

The results showed that Candida parapsilosis was the common isolate followed by C. albicans. The most effective antifungal agent against the organism in this study was ketoconazole and voriconazole. The species of Candida isolated in this study showed less bio-film forming capacity. This article shows the importance of studies regarding epidemiological, clinicomycological aspects of fungal infections and also the drug susceptibility of the organisms so that the treatment will be effective.

Key Messages €€ In this study, Candida parapsilosis was the common isolate and were susceptible to ketoconazole and

voriconazole €€ The biofilm forming capacity of the Candida species isolated in this study was less.

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97

ARTICLE 7

IL-17-mediated Immunity Controls Skin Infection and T Helper 1 Response during Experimental Microsporum Canis Dermatophytosis Burstein VL, Guasconi L, Beccacece I, et al. IL-17-mediated immunity controls skin infection and T helper 1 response during experimental Microsporum canis dermatophytosis.

J Invest Dermatol. 2018;138(8):1744-53.

Abstract Dermatophytosis is the superficial fungal infection of the skin wherein the fungus resides on the superficial layers of the epidermis. Sometimes, rarely the fungus can penetrate deeper and produce granulomatous reaction. The role of T helper cell type 17 and neutrophil immune response to dermatophytosis is known little. This study was performed to assess the role of Th17 cells and neutrophils recruitment in controlling superficial fungal infections. The results showed that Th17 cells regulate immunity by downregulating Th1 immune response and increase toward Th17 immune response.

COMMENT Dermatophytes are keratinophilic fungi which depend upon epidermal keratin for their carbon and nitrogen source. The control of superficial fungal infection by the immune system is not known much as there is paucity of studies. This study was conducted to assess the role of Th17 cells in the control of superficial fungal infections. There are two types of T cells, helper T cells and cytotoxic T cells. The role of T helper cells is to regulate the function of B cells and other cells whereas the role of CD8 T cells is to suppress the CD4 T cells.

In this study, a mouse model was deve­ loped and was inoculated with Micro­sporum canis in the superficial layers of the skin and the immune response was studied. The analysis showed that there was mild neutro­ phil response and invasion of the disease was controlled by the Th17 T helper cells. The results were compared with mice deficient in Th17 response. The results showed that M. canis induced Th17 cells and IFNγ was produced. The results showed that skin Langerhans cells contributed to the Th17 immune response and downregulated Th1 response.

Key Message €€ The results showed that Th17 cells regulate immunity by downregulating Th1 immune response and

increase toward Th17 immune response.

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98 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 8

In vitro Biofilms and Antifungal Susceptibility of Dermatophyte and Non‐dermatophyte Moulds Involved in Foot Mycosis Toukabri N, Corpologno S, Bougnoux ME, et al. In vitro biofilms and antifungal susceptibility of dermatophyte and non-dermatophyte moulds involved in foot mycosis.

Mycoses. 2018;61:79-87.

Abstract Onychomycosis and tinea pedis are commonly seen all over the world. The causative agents for the both can be dermatophytes and non-dermatophytic moulds. Both the agents mentioned above have the capability to form biofilms. This study was performed to assess the antifungal susceptibility of the above mentioned organisms and biofilms to the antifungal agents. The results showed that terbinafine was most effective against Fusarium solani. Econazole showed the maximum activity against biofilm producing organisms.

COMMENT This study was performed to assess the antifungal susceptibility of dermatophyte, non-dermatophyte moulds and biofilm producing agents to the antifungal agents. The fungal agents isolated from the patients were taken and the MIC for the antifungal agents like fluconazole, terbinafine, griseofulvin, econazole and itraconazole was analysed. The ability of the fungal isolates to produce biofilms was assessed and after 72 hours the results showed that almost all the organisms had the ability to form biofilm after 72 hours.

The results showed that terbinafine was most effective against Fusarium solani. Econazole showed the maximum activity against biofilm producing organisms. The above data can be utilised for treating tinea pedis and onychomycosis. The treatment of onychomycosis complicated by biofilm formation is difficult to treat and hence instead of the traditional surgical techniques for the treatment of the above can be replaced by topical/systemic agents.

Key Message €€ Econazole showed the maximum activity against biofilm producing organisms.

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99

ARTICLE 9

Microstructural Alterations in the Onychomycotic and Psoriatic Nail: Relevance in Drug Delivery Cutrín Gómez E, Anguiano Igea S, Delgado-Charro MB, et al. Microstructural alterations in the onychomycotic and psoriatic nail: Relevance in drug delivery.

Eur J Pharm Biopharm. 2018;128:48-56.

Abstract Nail alterations caused by disease processes like onychomycosis and psoriasis is well known. But the effect of the above disease processes in the diffusion and penetrance of the drugs is less known. This study was conducted to determine the microstructural alterations in the nails affected by onychomycosis and psoriatic nails and comparing with the healthy nails. The results showed that in both the disease processes the nail plate had more porosity, the maximum with onychomycosis compared to psoriasis.

COMMENT The structural abnormalities of the nail apparatus due to onychomycosis and psoriasis are well known. Very little data are available regarding the effect of the above changes with the drug delivery. It is believed that topical agents are not much useful as the sole therapeutic options for nail disorders due to the presence of the hard keratin in the nails leading to decreased penetration. This study was conducted to determine the microstructural alterations in the nails affected by onychomycosis and psoriasis and its relevance in drug delivery. The techniques like Raman spectroscopy, scanning electron microscope and other techniques were used to study the architecture

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of the nail carefully and also during the drug delivery. The results showed that when compared to healthy nails, onychomycotic nails have increased porosity and decreased disulfide bridges revealing the fact the fungal infection makes the nail more permeable to water and drugs. Also, the study showed that psoriatic nails also have increased porosity but they are less when compared to onychomycosis. The permeability to drug like clobetasol and ciclopirox was more in in-vitro permeation studies. This study gives new information regarding the microstructural alterations in the nail affecting the diffusion of the drugs topically used in the treatment of the above disorders.

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100 Year Book of Dermatology – 2019 Fungal Infections Key Messages €€ The

results showed that in both the disease processes the nail plate had more porosity, maximum with onychomycosis compared to psoriasis €€ The permeability to drug like clobetasol and ciclopirox was more in in-vitro permeation studies.

ARTICLE 10

Majocchi’s Granuloma: Current Perspectives Boral H, Durdu M, Ilkit M. Majocchi’s granuloma: Current perspectives.

Infect Drug Resist. 2018;11:751-60.

Abstract Trichophyton rubrum causes a rare infection namely Majocchi’s granuloma. The study has reviewed detail about the presentations, etiological factors and current treatment aspects. In the recent past, face has become the predominant site. Topical steroid usage for other dermatoses without bedside investigation is the main predisposing factor. Terbinafine is currently preferred drug.

COMMENT The study has tried to focus on the current trend in Majocchi’s granuloma (MG). MG is a rare anthropophilic fungal infection caused by Trichophyton rubrum. The two forms are inflammatory and granulo­ matous. The granulomatous form is seen in immunocompromised as nodular presentation in upper extremities. The inflam­ m atory form is seen in healthy subjects as papular form in lower limbs. The fungal organisms that can cause MG are Trichophyton rubrum, followed by T. mentagrophytes, T. violaceum, and T.  tonsurans. The rare causes are

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Epidermophyton floccosum, T. interdigitale, Micro­sporum canis, Aspergillus species and Nannizzia gypsea. Repeated shaving of lower extre­mities and continuous scratching in immuno­ compromised leads to disruption of the epidermal integrity thereby results in fungal entry into dermis. Inflammatory response sets in. The study has noticed that guinea pig being cryptic carriers can cause MG. Prolonged use of steroids for other dermatoses can decrease the Th1 mediated response resulting in MG. Adalimumab and vemurafenib are responsible of MG.

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Section 4: Miscellaneous Studies Face is the most common site of MG in immuno­competent and lower limbs in immuno­compromised. Apart from papular and nodular form, plaque and patch form also reported. AIDS patient even have palmoplantar hyperkeratosis and erythro­ dermic presentation of MG. In the last 6 years there is remarkable increase in MG cases. Fungal stains that are commonly used are GMS (Grocott-Gomori’s methenamine silver) and PAS (periodic acid-Schiff). Though GMS

101

has better contrast than PAS, time dependant and trained technician of GMS, make PAS superior. Fungal culture and advanced technique like internal transcribed spacer (ITS) sequencing aids the diagnosis. Nearly 50% of MG reported to terbinafine. Other systemic drugs that can be tried are itraconazole, griseofulvin voriconazole, and posaconazole. More studies are needed to formulate diagnostic and treatment guidelines for MG.

Key Messages €€ Patterns

of Majocchi’s granuloma differ between immunocompetent and immunocompromised individuals €€ Advanced technique like internal transcribed spacer sequencing aids the diagnosis of Majocchi’s granuloma.

ARTICLE 11

Superficial Fungal Infection among Patients with Immune Bullous Diseases Al-Dwibe H, El-Fergani N, El-Zurghany A, et al. Superficial fungal infection among patients with immune bullous diseases.

Libyan J Med Sci. 2017;1:16-7.

Abstract The study describes the superficial fungal infection in immunobullous diseases in Libya. Clinical and microscopic examinations were done. Mean age affected is in third to fourth decade. Higher incidence recorded in home makers, those living in rural areas and with diabetes. The most common fungal infection observed is distal subungual onychomycosis. Superficial fungal infections are common in pemphigus foliaceus group.

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102 Year Book of Dermatology – 2019 Fungal Infections COMMENT The study focuses on the superficial fungal infec­tion in immunobullous patients in Libya. Clinical, microscopic examinations and culture of the samples were done in bullous clinic. Nearly 50% were in third to fourth decade with female preponderance. Higher incidence of super­ficial infection recorded in home makers, those living in rural areas and with diabetes. Among the immunobullous diseases, pemphigus foliaceus rank first in having super­ ficial fungal infection followed by pemphigus vulgaris, dermatitis herpetiformis, bullous pemphi­goid and IgA pemphigus in order.

The most common fungal infection observed is distal subungual onychomycosis. The most common organism isolated is Candida from finger nails. Toe nails showed increase in Trichophyton verrucosum. Most of the patients are under steroid treatment for more than a year. Steroid sparing agent should be considered in the treatment of immunobullous diseases whenever applicable. As enough data are not their regarding superficial fungal infection in immunobullous diseases, further studies are warranted.

Key Messages €€ Pemphigus foliaceus ranks first in having superficial fungal infection followed by pemphigus vulgaris

and dermatitis herpetiformis

€€ Candida species is the common organisms isolated in immunobullous diseases.

ARTICLE 12

Emerging Atypical and Unusual Presentations of Dermatophytosis in India Dogra S, Narang T. Emerging atypical and unusual presentations of dermatophytosis in India.

Clin Dermatol Rev. 2017;1:12-8.

Abstract Dermatophytosis in the past decade widely present with atypical and unusual patterns. Extended systemic and topical antifungal are required. These emerging unusual presentations are because of complex interplay of agent, host and environment factors. Rosacea-like, seborrheic dermatitis-like, psoriasis-like and eczema-like are the varied unusual presentations of dermatophytosis. Hence, the study insisted dermatophytosis should be considered as great imitators.

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COMMENT In the last decade dermatophytosis widely present with atypical and unusual patterns. Such patients are difficult to treat and they have frequent relapses. Most often entire family is affected and causes financial burden. Atypical presentations become cumbersome for the dermatologist to treat. Complex interplay of agent, host and environment factors are responsible for unusual presentations and recalcitrant dermatophytosis. Substandard drugs are another factor. The list of organisms that cause atypical presentation are T.  rubrum,  Microsporum canis, T. menta­ grophytes, Trichophyton tonsurans and M. gypseum. Immune dysregulation by other derma­ toses like psoriasis and atopy are responsible for unusual presentations. Defective phagocytosis can lead to deep dermatophytosis, in which fungus affect the dermis and subcutis.

Sharing of towels, clothes, soap and washing clothes together are responsible for recurrent infections. Seborrheic dermatitis-like, psoriasis-like, eczema-like, polymorphic light eruptionlike and impetigo-like are the varied unusual presentations of dermatophytosis. Hence the study insisted dermatophytosis should be considered as great imitators. False negative KOH and fungal culture are frequent in these atypical cases. Diagnosis is by PAS staining fungi seen in upper layer of epidermis. Tinea recidivians or recurrent infection is mostly due to steroid abuse in steroid combination topical formulations. This results in resilient fungus, which responds initially with steroids and rebound after stopping treatment. Further studies are needed to create awareness regarding the emerging atypical presentation turning to be a major global burden.

Key Messages €€ Dermatophytosis should be considered as great imitators €€ Further

studies are needed to create awareness regarding the emerging atypical presentation turning to be a major global burden.

ARTICLE 13

Onychomycosis Secondary to Onychomadesis: An Underdiagnosed Manifestation Li M, Chen Z, Yin S, et al. Onychomycosis secondary to onychomadesis: An underdiagnosed manifestation.

Mycoses. 2017;60(3):161-5.

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104 Year Book of Dermatology – 2019 Fungal Infections Abstract Onychomadesis is the disease of nail matrix and is commonly seen in children with viral infections. Onychomycosis is the fungal infection of the nail apparatus and is rare in children. The study has found onychomycosis occuring secondary to onychomadesis. Fungal culture was done. The frequently isolated fungus is Candida glabrata. Bifonazole therapy was given.

COMMENT Nail disorders are less common in children compared to adults. Onychomadesis is the dis­ ease of nail in which proximal nail fold is sepa­ rated from nail bed. It is common in children. It is noninflammatory disorder of nail. Onychomycosis is the fungal infection of the nail apparatus and it is uncommon in children. The study evaluated the children with recent onychomycosis secondary to onycho­madesis. Total 16 cases were counted. Mean age was roughly 3 years. Female preponderance was seen. Thirteen patients had previous history of viral infections prior to the changes in nail.

Out of 16 cases, 11 showed positive culture and direct microscopy. C. parapsilosis, C. tropicalis, C. albicans and C. glabrata were isolated. C. glabrata is the most frequent fungi isolated from children. All children with onychomycosis secondary to onychomadesis were treated success­fully with topical bifonazole inhibiting ergosterol synthesis of fungal cell membrane. The study noted that onychomycosis, a rare nail finding in children, now found to be secondary to onychomadesis in children with previous history of viral infections.

Key Messages €€ Candida

glabrata is the frequent fungi isolated from onychomycosis secondary to onychomadesis in children €€ Onychomycosis responds to topical bifonazole therapy.

ARTICLE 14

Quantitative and Structural Analyses of the in vitro and ex vivo Biofilm-forming Ability of Dermatophytes Brilhante RS, Correia EE, Guedes GM, et al. Quantitative and structural analyses of the in vitro and ex vivo biofilmforming ability of dermatophytes.

J. Med. Microbiol. 2017;66:1045-2.

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Abstract Like bacteria, dermatophytes have the ability to produce biofilms. The study describes the structure and quantitative in vitro and ex vivo biofilm of the dermatophytes in the nail. The biofilm forming capacity of fungus like T. rubrum, T. tonsurans, T. mentagrophytes, M. gypseum and M. canis are evaluated.

COMMENT Dermatophytes have the ability to produce biofilm-like bacterial organisms. Biofilm is a collection of fungal hyphal mass embedded in an extracellular matrix. Thus biofilm prevents the penetration of the drugs resulting in antifungal resistance. The study evaluates the ability of fungal species to produce biofilm in the nail fragment. The structure and quantitative in vitro and ex vivo biofilm forming ability of the dermato­ phytes are analyzed. T. rubrum, T. tonsurans, T. mentagrophytes, M. gypseum and M. canis ability to form biofilm are evaluated. Biofilm

production was evaluated using crystal violet assay, confocal laser scanning, scanning electron microscopy and optical microscopy. Robust biofilms are produced by M.  gypseum, T. tonsurans and T. rubrum. Weakest biofilm is produced by M. canis. The study highlights the biofilm pro­duction by various fungal organisms thus making better understanding of pathophysiology of dermatophytosis. Future studies are needed to work on the composition and mechanism of formation of biofilms by dermatophytes.

Key Message €€ The

study highlights the biofilm production by various fungal organisms thus making better understanding of pathophysiology of dermatophytosis.

ARTICLE 15

Clinicopathological Features and Course of Cutaneous Protothecosis Tseng HC, Chen CB, Ho JC, et al. Clinicopathological features and course of cutaneous protothecosis.

J Eur Acad Dermatol Venereol. 2018;32(9):1575-83.

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106 Year Book of Dermatology – 2019 Fungal Infections Abstract Protothecosis is a very rare infection seen in tropical areas caused by achlorophyllic algae. The retrospective study evaluated the clinical, histopathological, course and outcome of protothecosis. Protothecosis should be taught as a differential diagnosis in an eczematous and ulcerative plaque in lower limb refractory to conventional treatments.

COMMENT This is a retrospective study which evaluates the clinical, histopathological, course and outcome of a rare achlorophyllic algae infection termed as protothecosis. It is an infection seen in tropical areas. The study analyzes twenty histopathology confirmed protothecosis. Protothecosis is seen mainly in elderly with mean age being seventy four years. The lesions were confined only to limbs. Twelve of the protothecosis patients had adrenal insufficiency; none had active malignancy at the time of diagnosis. The study noted concurrent scabies infestation in four of the protothecosis cases. The clinical features shower a

well defined erythematous plaque with interspersed punctate ulcers seen in limbs. Histopathology mainly showed a granulomatous response. Itraconazole showed an excellent response in 19 cases with one recurrence. Itraconazole was given for 2 weeks to 5 months. Though rare infection, proto­ t hecosis should be thought in elderly, immuno­ compromised individual with eczematous and ulcerative plaque in limb refractory to conventional treatments. The risk factors are steroid over usage and iatrogenic adrenal insufficiency. Infection can be confirmed by histopathology. Protothecosis responds well to itraconazole.

Key Messages €€ Protothecosis should be considered in elderly, immunocompromised adrenal insufficiency individual

with eczematous and ulcerative plaque in limb refractory to conventional treatments

€€ Protothecosis responds well to itraconazole.

ARTICLE 16

Pustular Tinea Manuum from Trichophyton Erinacei Infection Choi E, Huang J, Chew KL, et al. Pustular tinea manuum from Trichophyton erinacei infection.

JAAD Case Reports. 2018;4(6):518-20.

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Section 4: Miscellaneous Studies

107

Abstract Trichophyton erinacei is a rare zoonotic fungus from Trichophyton mentagrophytes complex. It usually causes tinea infection on exposure to hedgehog. This is a rare case report of pustular tinea mannum caused by Trichophyton erinacei.

COMMENT Trichophyton erinacei is a zoonotic dermatophyte seen in New Zealand, Australia, Europe and Africa. This article is a rare case report of pustular tinea mannum caused by Trichophyton erinacei for the first time in Southeast Asia. A known case of HLA-B27 positive spondyloarthropathy on treatment with methotrexate and oral steroids presented with itchy painful pustules over the palms. Patient gave a history of plant prick by cactus sap. Other dermatological examination found to be normal. Differentials thought were contact dermatitis to cactus sap and pustular psoriasis. Investigations such as pus culture and fungal culture were done. Patient was started on oral antibiotics and topical steroids

and antifungals. Culture for bacteria and mycobacteria found to be negative. Histopathology and fungal culture showed positive Trichophyton erinacei. On elaborative history, it was found that she had exposure with hedgehog following which she developed pustules over palms. She was started on oral terbinafine for a 2 weeks period with dramatic response. Trichophyton erinacei is a zoonotic infection seen in hedgehog and elephants. Most common site is palms and other rare sites are face and scalp. Animals should be treated simultaneously. With increased domestic pets, Trichophyton erinacei infec­ tion should be sought as differentials in pustules of palms.

Key Message €€ For

pustular lesion over palms index suspicion of Trichophyton erinacei infection is necessary with increasing exotic domestic pets.

ARTICLE 17

Tinea of Vellus Hair: A Diagnostic and Therapeutic Challenge Eksomtramage T, Aiempanakit K. Tinea of vellus hair: A diagnostic and therapeutic challenge.

BMJ Case Rep. 2018;2018.

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108 Year Book of Dermatology – 2019 Fungal Infections Abstract Rare forms of common diseases are often difficult to diagnose and treat. This article is about one such disease namely tinea of vellus hair. Microscopic and fungal culture was found to be positive. Clinical improvement was seen well with oral antifungals.

COMMENT The vellus hair is scarcely seen thin light coloured hair seen over the face and body. Dermatophytic infection of vellus hair is very rare form of tinea infection. This article is about rare case report of 26 years female with tinea of vellus hair with characteristic clinical feature and micro­ scopic study. Tinea of vellus hair though commonly seen in children, it is rarer in adults. The predisposing factors are topical steroid usage, contact with pet animals, and resistance to antifungals. The usual site is face but any area of the body can be affected. The clinical presentation is erythematous itchy scaly plaque with follicular pustules. The reported case has history of topical steroid application. Dermatological examination revealed a single well defined reddish annular

scaly plaque with few pustules present over right cheek. The differential diagnoses sought were Majocchi’s granuloma, contact dermatitis and granulomatous diseases. Majocchi’s granuloma is differentiated with history of repeated shaving, commonly seen over lower extremities, histopathology and fungal culture. Potassium hydroxide microscopy and fungal culture are definite diagnosis for tinea of vellus hair. KOH examination showed arthrospores in the vellus hair. The organisms causing tinea of vellus hair are Trichophyton species and Microsporum species Systemic antifungal itraconazole responds well to tinea of vellus hair. Tinea of vellus hair is a rare form of dermatophytosis that responds well to systemic antifungals.

Key Messages €€ Tinea

of vellus hair is a rare form of dermatophytosis with erythematous plaque with pustules studded on it €€ Systemic antifungals are the treatment of choice.

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Section 4: Miscellaneous Studies

109

ARTICLE 18

Relationship of Amino Acid Concentrations in Blood with Occurrence of Dermatophytosis Khiavi FH, Gharachorlu A. Relationship of amino acid concentrations in blood with occurrence of dermatophytosis.

Journal of Pakistan Association of Dermatology. 2018;28(2):129-33.

Abstract This study compares the level of free amino acids in healthy individual and those with dermatophytosis. The levels of free amino acids are assayed with the help of high performance liquid chromatography. The study emphasizes the role of free amino acids in dermatophytic pathogenesis.

COMMENT Dermatophytosis is a most common super­ ficial fungal infection prevalent worldwide. Multiple studies are done on dermatophytosis. This original article compares the level of free amino acids in healthy individual and those with dermatophytosis. Dermatophytes penetrate the upper layer of the skin by germ tube formation. During the process of infection proteins are cleaved into amino acids. These amino acids are used as food source by the dermatophytes. This states a relationship of some amino acids in dermatophytosis, however studies regarding this are lacking. The current study assesses the relationship of various amino acids in dermatophytosis. The study population includes 40 myco­ logically proven dermatophytosis and 44 sex

and age matched healthy individuals as controls. The levels of free amino acids are assayed with the help of high performance liquid chromatography. It was found out that about 90% of dermatophytosis patients showed increased amino acid levels compared to their healthy controls. The amino acids such as tyrosine, phenylalanine, glutamine and asparagine were significantly higher in dermatophytic individuals. Methionine does not exhibit any noticeable difference among the two groups. This article suggests the role of amino acids in dermatophytic pathogenesis. Further studies are needed to find the exact role of amino acids in pathogenesis of fungal infection.

Key Messages €€ The study emphasizes the role of free amino acids in dermatophytic pathogenesis €€ The amino acids such as tyrosine, phenylalanine, glutamine and asparagine were significantly higher

in dermatophytic individuals.

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110 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 19

Assessment of the Subtilisin Genes in Trichophyton rubrum and Microsporum canis from Dermatophytosis Robati KA, Khalili M, Hazaveh SJH. Assessment of the subtilisin genes in Trichophyton rubrum and Microsporum canis from dermatophytosis.

Comp Clin Pathol. 2018;27:1343.

Abstract The study describes the presence of subtilisin genes in Microsporum canis and Trichophyton rubrum from the dermatophytic infections. Subtilisin genes have keratinolytic activity. With the help of PCR, subtilisin gene has been described. Subtilisin gene plays a role in pathogenesis of dermatophytic infections.

COMMENT The study describes the presence of subtilisin gene in Microsporum canis and Trichophyton rubrum decides the dermatophytic infections. Subtilisin gene codes for serine proteases which have a keratinolytic activity on the fungal species. This subtilisin gene makes the fungal species to adhere and degrade keratin during the infective process. The study isolates the dermatophytes both from animal and human dermatophytosis. Laboratory examination and KOH microscopy were used to identify the isolates. With PCR specific primers, the dermatophytic isolates

were analyzed for the presence or absence of subtilisin gene. The present study describes the most frequency of subtilisin gene families. About 94% of the isolates showed one virulence gene atleast. Statistical significance was noted between the presence of subtilisin gene and dermatophytic infections. The study is the first to describe the presence of subtilisin gene in dermatophytic infections in Iran. The study concludes stating that subtilisin gene plays a role in pathogenesis of dermatophytic infections.

Key Messages €€ Subtilisin gene plays a role in pathogenesis of dermatophytic infections €€ The

presence of subtilisin gene in Microsporum canis and Trichophyton rubrum decides the dermatophytic infections.

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111

ARTICLE 20

Tinea Corporis Caused by Trichophyton equinum in a Rider and Review of Literature Veraldi S, Genovese G, Peano A. Tinea corporis caused by Trichophyton equinum in a rider and review of the literature.

Infection. 2018;46(1):135-7.

Abstract Equine dermatophytosis is dermatophytic infection in horses caused by Trichophyton equinum. This zoophilic dermatophyte causing fungal infection in humans is very rare. This article is about a rare case report of dermatophytic infection in a horse rider and the etiological agent found to be Trichophyton equinum.

COMMENT In the past Trichophyton equinum is strictly found to be zoophilic dermatophytosis. This article is about a rare case report of dermato­ phytic infection in a horse rider and the etiological agent found to be Trichophyton equinum. The current article report tinea corporis in gluteal region in a horse rider who used to ride horse in a bare back with short trousers. The patient would have acquired infection from horse. KOH microscopy and fungal culture was found to be positive. Culture medium used to isolate Trichophyton equinum species are SDA agar and potato dextrose agar. This article presents the review of clinical

presentations and epidemiological features of this zoophilic dermatophyte causing a human infection. The patient responded well to systemic antifungals. Horse rider should be insisted about full covered clothing while horse riding to avoid acquiring dermatophytic infection. Hygiene should be maintained while handling horses. Once the case diagnosed with dermatophytic infection by Trichophyton equinum it is must to treat the equine dermatophytosis in order to prevent recurrences. This article emphasizes that zoophilic dermatophyte namely Trichophyton equinum are found to cause human dermatophytic infection.

Key Messages €€ Equine dermatophytosis by Trichophyton equinum is found to cause human dermatophytic infection €€ Protective clothing should be emphasized to horse riders.

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112 Year Book of Dermatology – 2019 Fungal Infections

ARTICLE 21

In vitro Models of Dermatophyte Infection to Investigate Epidermal Barrier Alterations Faway É, Lambert de Rouvroit C, Poumay Y. In vitro models of dermatophyte infection to investigate epidermal barrier alterations.

Exp Dermatol. 2018;27(8):915-22.

Abstract Dermatophytosis prevalence is increasing day-by-day despite the treatment options available. Dermatophytic pathogenesis starts by disruption of the epidermal barrier. The knowledge to understand the exact pathogenesis is lacking by discrepancy between in vivo and research models. This article focuses on the human skin equivalents which describes the exact relationship of epidermal barrier integrity and dermatophytic infection.

COMMENT Dermatophytosis is distributed worldwide and its prevalence is exclating despite the various treatment options available. The knowledge to understand the exact pathogenesis of dermatophytosis is lacking due to discrepancy between in vivo and research models. Monolayer cell cultures do not fulfill the keratinization process which is essential to understand the adherence and invasion of the fungus. This article focuses on the human skin equivalents which describes the exact relation­ship of epidermal barrier integrity and dermatophytic infection. Dermatophytosis differs between species to species hence animal models such as mouse and guinea pig

won’t help in such a way to understand the human dermatophytic pathogenesis. Human skin equivalents mimic the human skin without affecting the ethical limitations. Human skin equivalents are solely made of keratinocytes this help further to understand the exact patho­ genesis. The disadvantage is absence of sebum, microbiome and favorable culture conditions make them more susceptible to dermatophytic infections compare to normal counterparts. Human skin equivalents co cultured with immune cells can be an excellent model to assess the invasion, adherence of the fungus and epidermal integrity.

Key Messages €€ Human

skin equivalents describe the exact relationship of epidermal barrier integrity and dermatophytic infection €€ Human skin equivalents cocultured with immune cells can be an excellent model to assess the invasion, adherence of the fungus and epidermal integrity.

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INDEX The letter P after entry denotes Plate.

A Acacia sinuata 66 Acalypha indica 66 Acanthosis nigricans P 6 Acetaminophen 55 Acetocopalic acid 43 Acetylsalicylic acid 55 Acremonium species 15 Ageratina pichinchensis lacquer 72 Allylamine derivatives 46 Alpha bisabolol 77 Alpha trans-bergamotol 77 Amides 67 Amino acid 109 Amorolfine 21, 74, 75, 76 Amphotericin B 18, 45-47, 66 Analgesic drugs 54 Anidulafungin 61 Anti-biofilm effects 63 Antibiotic production 67 Anticandidal activity 54 agent 64 Antidermatophytic activity 66 Antifungal action 48 activity 1, 28, 43, 54, 59, 60, 64, 66, 68, 69, 76, 81 agent 35, 48, 54, 60, 79, 95, 98 combination of 56 new 95 safety and efficacy of 53 systemic 13 compounds 47 discovery of 50 cream 21 derivative of 64 drug 56, 84 natural 81

INDEX_Yearbook of Dermatology-Fungal infections.indd 113

effect 35, 52, 54 ougon for 50 significant 50 efficacy 45 failures, prevention of 79 groups of 86 itraconazole, systemic 108 luliconazole 84 medication 4 potential of linalool against 48 preparation 66, 68 property 81 resistance 18 in dermatology 55 sensitivity to 8 susceptibility 96, 98 therapeutic failures 79 therapy 57 topical 13 treatment 62, 82, 92 combination 55 Anti-inflammatory property 30, 87 Antimicrobial activity, broad spectrum 52 Antimicrobial agents 52 Antioxidant property 67 Aromatic compound, sidechain 69 Arylazothiazole 69 Arylhydrazothiazole 69 Asparagine 109 Aspergillus species 11, 15, 61, 100 Azole antifungals 47 newer 61 topical 46

B Bacterial organisms 105 Beta caryophyllene 77 Bifonazole 74, 75 therapy 104 Biofilm formation 61, 63 ability, evaluation of 63 producing organisms 98 production 56 Biosynthesized silver 51 Blood 109 Bullous disorders 80 Burning 22

C Caffeic acid 68 Candida albicans 9, 39, 42, 51, 60, 63, 69, 96, 104 in nails 41 glabrata 55, 63, 64, 104 isolated 96 krusei 59, 60 lusitaniae 63 parapsilosis 59, 60, 63, 96, 104 species 2, 9, 27, 42, 52, 58-61, 63, 64, 86, 92, 96, 102 new antifungal against 64 resistant 55 strains different 63 species of 63 tropicalis 55, 104 yeasts 2, 76 Candidal species 64 Candidial infections 61

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114 Year Book of Dermatology – 2019 Fungal Infections Candidiasis invasive 61 treatment of 77 Capitis favosa patients 5 Carbon dioxide, fractional 49, 56 Carvacrol and thymol 47 Caspofungin 61 Caulerpa sertularioides 28 Causative agents 15 Cellular activities 35 Chemotherapeutic agents 43 Chicago sky blue stain 41 Cibotium barometz 28 Clobetasol 100 Clotrimazole 86 Communicable disease 29 Coniferous resin, natural 72 Constituent copalic acid 43 Copaiba oil 43 Copaifera genus 43 Copalic acid 43 Croton tricolor 77 stem 76 Cryptococcus neoformans 51, 52 species 52 Cutaneous fungi 69 Cutaneous irritation, local 86 Cutaneous mycosis 30 eberconazole, treatment of 86 inflamed 30 treatment of 30 Cutaneous protothecosis, course of 105 Cysteine amino acid 53 Cytotoxic T cells 97

D Dematophytosis, classification of 94 Dermatitis, contact 108 Dermatophyte 6, 11, 15, 16, 27, 37, 38, 43, 45, 50, 51, 58, 65, 67, 84, 93, 94, 97, 98 ability of 104 African species of 3 anthropophilic 24

INDEX_Yearbook of Dermatology-Fungal infections.indd 114

detection of 41 diagnosis of 34 infection 7, 112 drug-resistant 65 inhibition of 44 isolates 72 clinical 74 multidrug-resistant 65 non 27 penetrate 109 prevalence of 31 related 94 species of 1, 7, 15 tandem repeat database 95 tested 51 Dermatophytic infection 24, 25, 29, 65, 68, 70, 71, 90, 110, 112 Dermatophytic isolates 110 Dermatophytic nail infection 16 Dermatophytic reinfections 85 Dermatophytoma 4 formation of 4 Dermatophytosis 11, 23, 20-25, 29, 38, 40, 44, 45, 47, 64, 69, 81, 97, 102, 109, 110 chronic 58 diagnosis of 37 diffuse 77 drug-resistant 84 in hosteller, disseminated P3 mimicking lichen nitidus P 3 of hair, management of 70 predominantly affecting area P4 prevalence 112 relevance in recalcitrant 45 severe 20 treatment 1, 43, 44, 46, 47, 58, 79, 81, 86 failure in 18 Diabetic and non-diabetic patients 9 Dimethyl fumarate therapy 77, 78 Diode laser 13 Dipyrithione 78, 79

Dystrophic onychomycosis, total 39

E Eberconazole 30, 82, 83, 86, 88 efficacy of 83 nitrate 30, 82 quality of life of 88 safety of 83 Echinocandin 47, 56, 60 long-acting 61 Econazole 84, 98 Eczema 80, 102, 103 Efinaconazole 71-73 Endothrix organism 23 Enzyme 36 Epidermal barrier 112 alterations 112 Epidermophyton 56, 58, 93 floccosum 16, 32, 39, 46, 75, 81, 84, 100 Epiglobulol 77 Ergosterol synthesis 65, 66, 69 inhibiting 66 Erythematous itchy 108 Erythroderma 80 Esophageal candidiasis 61 Ethyl cellulose, investigation of 82 Eugenol 47 Ex vivo biofilm-forming 104 Extracellular matrix 57 Eye, nose and mouth, mucocutaneous junctions of P 2

F Feet-washing behavior 19 Finger nails 49, 92 Flavonoids 59 Fluconazole 1, 18, 46, 48, 49, 54, 63, 64, 70-73, 98 resistances 64 resistant trichophyton rubrum 48 Flucytosine 47 Foot mycosis 98 powder, application of 85

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Index Formaldehyde fumigation 85 Fresh patches over healed area P 10 Fungal cell 43, 66, 68 Fungal concentrations 66 Fungal culture 7, 34, 104 disadvantage of 34 Fungal disease 27 Fungal elements 48 Fungal growth 44 Fungal infection 2, 15, 23, 38, 42, 47, 55, 66, 80, 95, 101, 104 anthropophilic 100 chronic 57 coexistence of 91 common 24 diagnosis of 42 effect in 87 invasive 95 management of 70 of feet, management of superficial 85 of hair and nail 70 superficial 25, 29, 31, 32, 47, 58, 85, 86, 97, 101, 102 treatment of 51 Fungal nail infection 16, 73, 87 Fungal organisms 36 Fungal species 95 of onychomycosis 9 Fungal therapy 82 Fusarium 2 and candida 87 solani 98 species 2, 15 Fusidic acid 67

G Glabrous skin 90 Glutamine 109 Glycosidic saponin 47 Glyoxylate cycle 68 Gold nanoparticles 51 Granulomatous diseases 108 Griseofulvin 46, 65, 70, 84, 98 acts 65 voriconazole 101 Grocott-Gomori’s methenamine silver 101

INDEX_Yearbook of Dermatology-Fungal infections.indd 115

Guinea pig 78 dermatophytosis models 78

H Hair follicle 90 Health Education Programs 29 Healthy population, normal 8 Helper T cells 97 Hepatotoxicity 61 Herbal preparations, use of 66 Heterocyclic benzofurans 56 Human cells 35 Human dermatophytic infection 111 pathogenesis 112 Human immunodeficiency virus 31 infection 8 Human keratinocytes, minimal effect 51 Human pathogenic fungus 52 Human skin equivalents 112 Hydrolytic enzymes 36

I Ibuprofen 55 Immune bullous diseases 101 system 97 Immunomodulatory agents 56 Immunosorbent assay 36 In silico characterization 94 In vitro additive effect 65 In vitro antidermatophytic activity 27 In vitro antifungal 5 activity 72 In vitro biofilm 98 forming 104 In vitro models 112 In vivo antifungal activity 78 Indocyanine green 39 Infection recurrent 71 severe 80 treatment resistant 47 Infectious disease 31 risk of 31 Inflammation, severe 70

115

Inflammatory reactions 36 Intralesional steroids 91 Invasive infections, development of 61 Isavuconazole 54 Itching, reduced 22 Itraconazole 1, 18, 46, 49, 54, 70-75, 84, 98, 101

K Kampo medicine 50 Kappaphycus alvarezii 28 Keratinophilic fungi 56, 93 Kerion P 1 Ketoconazole 18, 48, 66, 84, 96 Kojic acid 67

L Langerhans cells 97 Lanoconazole 72, 73, 84 Laser assisted delivery of topical tazarotene 49 Leg lesion 93 Lichen metabolites 81 Licochalcone 68 Liver enzymes, abnormal 70 Luliconazole 64, 72, 73 Lupus autoimmune overlap syndrome 93 syndrome 92 Lymphocyte counts 78 Lymphopenia 78

M Majocchi’s granuloma 100, 108 Malassezia furfur 83 pachydermatis 66 species 59 yeasts 86 Mammalian cells 68 Marine algae 27, 28 Medicinal plants 27, 28, 47, 66 effective 47 Medicine, traditional 47 Melastoma malabathricum 28 Meloxicam 55 Mentioned 57 Metamizole 55

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116 Year Book of Dermatology – 2019 Fungal Infections Methotrexate 93 Methylene blue 39 Micafungin 61 Miconazole 86 Microbiological resistance 56 Microsporum 52, 56, 58, 110 audouinii 3, 25, 81 canis 1, 27, 36, 59, 60, 65, 75, 81, 97, 100, 103, 105, 110 dermatophytosis 97 infection 36 strains 75 gypseum 1, 43, 45, 65, 69, 81, 103, 105 nanum 81 species 93, 108 Mometasone furoate 30 Monolayer cell cultures 112 Mucocutaneous candidiasis 64 Muehlenbeckia platyclada 28 MVAL enzyme 7 Mycosel agar 16

N Nail alterations 99 dermatophyte infections, treatments in 58 disorder 71, 104 dystrophy, total 26, 27 involvement 91 of psoriasis 91 noninflammatory disorder of 104 plate 71 psoriasis 91 severity of 91 Nannizzia gypsea 100 nana 93 perplicata 92, 93 Nanoparticles action of 63 role of 51 Natural treatments 72 Nitric oxide-releasing drug 12 Nonablative laser 13 Non-albicans species 64 Nonantifungal agents 56

INDEX_Yearbook of Dermatology-Fungal infections.indd 116

Non-Candida albican species 9 Non-dermatophyte 11, 15, 92, 98 organisms 11, 38, 42 Non-dermatophytic fungi 91 Nondiabetic population 9 Nuclear ribosomal 94

O Onychomadesis 103, 104 Onychomycosis 4, 9, 10, 11, 15, 23, 34, 38, 40, 42, 49, 53, 54, 57, 62, 64, 71, 74, 76, 87, 98, 103, 104 diagnosis of 34, 38, 40, 42 in children 53 treatment of 54 infection 34 cases of 96 management of 13, 71 mixed 26, 27 pathogens 14 therapy for 57 treatment of 4, 5, 13, 49, 54, 57, 62, 87 Oral antifungals 71, 75, 76 Oral bioavailability, poor 61 Organ transplant recipients, solid 20 Orocutaneous fungi 8 Ozone application 85

P PCR-RFLP technique 39 Pediatric onychomycosis 73 treatment of 73 Peltigera praetextata 81 Pemphigus foliaceus group 101 Periodic acid-Schiff 101 Personal hygiene, lack of 29 Phaffia rhodozyma 52 Phenothiazinium dye 40 Phenylalanine 109 Photodynamic therapy 39, 57, 58, 59 Photodynamic treatment with curcumin 44 Photosensitising agents 44 Phyllanthus reticulatus 66

Phylogenetic relation 94 Pityriasis versicolor 83, 88 treatment for 83 Plinia cauliflora 59, 60 Polyene derivatives 56 Polymerase chain reaction 34, 38 Posaconazole 54, 101 Potassium hydroxide 23, 108 microscopy 26 Povidone iodine 57 Pramiconazole 58 Proton pump inhibitors 56 PRP8 intein in dermatophytes 93 Psoriasis 80, 99 Psoriatic nail 91, 99 Public health problem 87 Pustular tinea mannum 106, 107

R Raman spectroscopy 99 Refractory dermatophytosis 80 Retinoid tazarotene 49 Rezafungin acetate 61 Rhapis excelsa 28

S Sabouraud’s dextrose agar 16, 45 Sabouraud’s glucose 45 Sanitization powders 85 Scropulariopsis brevicaulis 15 Scutellaria 50 Scytalidium dimidiatum 15 Senna alata 66 Senna auriculata 66 Sertaconazole 21, 22 cream 21 Shoe acts, infected 85 Shoe and sock sanitization method for 85 role of 85 Simvastatin 56 Skin dermatophyte infections, treatments in 58 dextrose, keratinized 67

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Index disorders 10 fungal infection, risk factors of superficial 29 infection, superficial 11, 29 Spectrum antifungal agent 46 Steroid 30, 80 application P 9 combination, result of topical P9 modified tinea corporis P 9 potent topical 24 topical P 9, 18 Sterol metabolism 35 Subtilisin gene 110 Subungual onychomycosis 39, 101 Sulfones 67 Syzygium myrtifolium 28

T T cells, types of 97 Tacrolimus 56, 74 Tavaborole 4, 71 Tazarotene 49 Terbinafine 1, 18, 46, 47, 49, 65, 70-75, 84, 88, 98 acts 65 efficacy 83 resistance to 46 resistant isolates 84 safety of 83 Tetranortriterpenoid 47 Thiazole derivatives 69 Tinea coporis with scaling and erosion P 5 folliculorum 90 glutealis P 8 incognito P 9 manuum, retained dermatoglyphics in P 8 of glabrous skin, complicating 90 versicolor 83, 88 Tinea axillaris P 6 mimicking erythrasma P 6 Tinea capitis 1, 3, 6

INDEX_Yearbook of Dermatology-Fungal infections.indd 117

in adult glabrous type of P 1 mimicking psoriasis P 1 Tinea corporis P 9, P 10, 18, 81, 90, 92 extensive P 4 in diabetic P 4 in HIV-positive woman, multiple patches of P 5 in infant P 2 in painter mistaken for eczema P 2 in pregnant woman, multiple patches of P 5 inflammatory type of P 2 mimicking annular erythema P 3 herald patch of pityriasis rosea P 3 psoriasis in patient with psoriasis, plaques of P2 psoriasis, inflammatory type of P 3 noninflammatory type of P 2 of thigh P 5 of waist with lichenification P6 over knees in diabetic P 4 with islands of normal skin, extensive P 4 with topical salic acid preparation, eczematisation of P 4 Tinea cruris P 6, 21, 81 in young boy P 6 unilateral P 7 with active margin P 7 with flexural psoriasis P 7 with postinflammatory pigmentation and active margin P 7 with tinea genitalis P 8 Tinea faciei 24 masquerading atopic dermatitis P 1 mimicking impetigo circinata P 1 infective eczema P 1

117

Tinea infection 108 causes 107 Tinea pedis 12, 19, 32, 81, 85, P8 causes 32 interdigital 2 proportional to 19 treatment of 12 visual diagnosis of 10 Tinea unguium 10, P 8 onychomycosis 16 Tioconazole application of 49 topical 49 Toe nails 49, 62, 92 Toenail onychomycoses, clinical laser treatment of 62 Topical therapy, role of 73 Transmission electron microscopy 35 Triamcinolone acetonide 74 Triazole 46 efinaconazole 72 Trichophyton 56, 58, 93 equinum 111 erinacei 107 infection 106, 107 interdigitale 7, 14, 28, 42, 52, 53, 73, 84, 100 antifungal for 72 mentagrophytes 9, 15, 16, 18, 32, 35, 43, 46, 51, 65, 66, 69, 75, 81, 100, 103, 105 complex 107 organisms 52 rubrum 9, 7, 14-16, 18, 27, 28, 31, 32, 39, 40, 42, 43, 46, 48, 50, 51, 59, 60, 65-68, 73, 75, 78, 79, 81, 94, 95, 100, 103, 105, 110 antifungal for 72 cycle of 68 glyoxylate cycle of 68 schoenleinii 5, 6 soudanense 16, 25 species 16, 28, 108 strains 75

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118 Year Book of Dermatology – 2019 Fungal Infections tonsurans 16, 28, 39, 81, 84, 100, 103, 105 verrucosum 16, 17, 102 infection, epidemiology of 17 violaceum 1, 16, 22, 23, 81, 100 infection 23 Triintsin 52 effect of 52 structure of 53 Tyrosine 109

INDEX_Yearbook of Dermatology-Fungal infections.indd 118

U Unicellular aleuriospores 92

V Vellus hair infection of 108 tinea of 107, 108 Vernonia amygdalina 28 Vero cells, viability of 28 Verrucosum 46 Voriconazole 18, 54, 61, 84, 96

W Wrightia tinctoria 66

Y Yeasts 15, 27, 38, 42 biodiversity of 11 incidence of 11

Z Zoophilic dermatophyte infections 36

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PLATE 1

FIGURE 1: Kerion.

FIGURE 4:  Tinea faciei mimicking infective eczema, note tinea capitis mimicking alopecia areata.

FIGURE 2:  Tinea capitis in an adult mimicking psoriasis.

FIGURE 5:  Tinea faciei masquerading as atopic dermatitis.

FIGURE 3:  Glabrous type of tinea capitis in an adult.

FIGURE 6:  Tinea faciei mimicking impetigo circinata.

Color plates.indd 1

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PLATE 2

FIGURE 7:  Tinea faciei involving mucocutaneous junctions of eye, nose and mouth.

FIGURE 10:  Inflammatory type of tinea corporis.

FIGURE 8:  Tinea corporis in an infant.

FIGURE 11:  Tinea corporis in a painter mistaken for eczema.

FIGURE 9:  Noninflammatory type of tinea corporis.

FIGURE 12:  Plaques of tinea corporis mimicking psoriasis in a patient with psoriasis.

Color plates.indd 2

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PLATE 3

FIGURE 13:  Tinea corporis mimicking annular erythema.

FIGURE 15:  Inflammatory type of tinea corporis mimicking psoriasis.

FIGURE 14:  Tinea corporis mimicking herald patch of pityriasis rosea.

FIGURE 16:  Dermatophytosis mimicking lichen nitidus.

FIGURE 17:  Disseminated dermatophytosis in a hosteller.

Color plates.indd 3

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PLATE 4

FIGURE 18:  Extensive tinea corporis.

FIGURE 19:  Extensive tinea corporis with islands of normal skin.

FIGURE 21:  Bilaterally symmetrical Tinea corporis over the knees in a diabetic.

FIGURE 20:  Dermatophytosis predominantly affecting the area covered by tight garment.

FIGURE 22:  Eczematisation of tinea corporis with topical salic acid preparation.

Color plates.indd 4

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PLATE 5

FIGURE 23:  Tinea corporis in a diabetic.

FIGURE 24:  Multiple patches of tinea corporis in pregnant woman.

FIGURE 26:  Tinea corporis of the thigh—note the unilateral involvement.

FIGURE 25:  Multiple patches of tinea corporis in HIV-positive woman.

FIGURE 27:  Tinea coporis with scaling and erosion.

Color plates.indd 5

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PLATE 6

FIGURE 28:  Tinea corporis of the waist with lichenification.

FIGURE 30:  Tinea axillaris in a patient with acanthosis nigricans.

FIGURE 29:  Tinea axillaris mimicking erythrasma.

FIGURE 31:  Tinea cruris in an young boy.

FIGURE 32:  Tinea cruris.

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PLATE 7

FIGURE 33:  Tinea cruris with active margin.

FIGURE 34:  Tinea cruris along with flexural psoriasis.

FIGURE 35:  Unilateral tinea cruris.

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FIGURE 36:  Tinea cruris with post inflammatory pigmentation and active margin.

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PLATE 8

FIGURE 37:  Retained dermatoglyphics in tinea manuum.

FIGURE 40:  Tinea glutealis showing central clearance over the right buttock.

FIGURE 38:  Tinea pedis.

FIGURE 41:  Tinea cruris with tinea genitalis.

FIGURE 39:  Tinea glutealis.

FIGURE 42:  Tinea unguium—white superficial onychomycosis.

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PLATE 9

FIGURE 43:  Increase in size of lesion following steroid application.

FIGURE 45:  Topical steroid modified tinea corporis showing ring within ring.

FIGURE 44:  Note the striae as a result of topical steroid combination.

FIGURE 46:  Tinea incognito where the original morphology is almost lost.

FIGURE 47:  Steroid modified tinea corporis.

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PLATE 10

FIGURE 48:  Note fresh patches over healed area in a recurrent case.

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FIGURE 49:  Note the excoriations and erosions secondary to topical application in tinea corporis.

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