DM Thappa - Essentials in Dermatology, 2nd Edition

Essentials in Dermatology (with Multiple Choice Questions)

Essentials in Dermatology (with Multiple Choice Questions)

Second Edition

Devinder M Thappa

MD, DHA, MNAMS, FIMSA

Professor and Head Department of Dermatology and STD Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Pondicherry, India

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Essentials in Dermatology (with Multiple Choice Questions) © 2009, Jaypee Brothers Medical Publishers All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the author and the publisher. This book has been published in good faith that the material provided by author is original. Every effort is made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters are to be settled under Delhi jurisdiction only.

First Edition: 2003 Second Edition: 2009 ISBN 978-81-8448-558-5

Typeset at JPBMP typesetting unit Printed at Ajanta

Preface to the Second Edition The second edition of Essentials in Dermatology (with Multiple Choice Questions) is being published 6 years after the appearance of the first edition. The encouraging response to the first edition prompted me to revise the book, keeping in view the comments received, and changing trends in the field of dermatology. This new edition incorporates differential diagnosis for each entity or group of entities to further understand the subject critically. Three new chapters—Skin in Systemic Diseases, Skin Changes of Pregnancy and Old Age, and Antiretroviral Therapy (ART) have been added. The existing chapters have been updated and treatment guidelines revised. Newer entities have been included under various chapters, but not at the cost of brevity and conciseness. For better understanding of the text, better photographs and clinical illustrations have been incorporated. The section on multiple choice questions has been considerably expanded, and this section has been divided into two—for PG entrance examinations and for postgraduates in dermatology. Additional mnemonics have been included in the useful medical mnemonics section. The objective of this edition remains the same—to serve as an aid for beginners in dermatology and those aspiring for PG entrance examinations. The making of the revised edition of this book involved a number of people besides myself. Many of the chapters were revised with inputs from my senior residents Dr Rashmi Kumari, Dr Amiya Kumar Nath and Dr Abarna Devi and junior residents Dr Nidhi Singh, Dr Abhijit Chougule, Dr Kishan Kumar Agarwal, Dr Balaji Adityan, Dr Sowmya Kaimal and Dr Sakthi Kandan. The photographs utilized in the book have been possible due to the Medical Illustration Department of the hospital, and the digital cameras of my postgraduates, making the new edition a colorful experience. My laboratory technician Mr Samsudeen deserves a mention for his skill in the staining and preparation of laboratory material for photomicrography. The final making of this edition has involved the support and cooperation of all my esteemed colleagues, patients and the forgotten names of residents (who worked for the first edition of the book). As always, this edition is open to constructive criticism and suggestions for its further improvement. Devinder M Thappa

Preface to the First Edition Dermatology, the science of the skin, was one of the many specialties, which evolved from general internal medicine during the course of the nineteenth century. In India, recognition of dermatology as a specialty distinct from internal medicine is recent; it has still not grown to its full stature in practice and teaching. In spite of having some share in the curriculum, dermatology remains a neglected subject because of its non-inclusion in the qualifying examination at MBBS level. There has been an explosion of knowledge—easily documented by the size of standard dermatology textbooks, whose length has increased from an average of 1000 pages to the most recent editions of Fitzpatrick and of Rook, which are more than 3000 and 3600 pages, respectively. Expansion has been greater on the surgical and cosmetic side of the specialty, which barely existed 50 years ago. Such vast knowledge is difficult to grasp in 3 years course of MD dermatology, venereology and leprology, sometimes may be at the cost of another. So there was need for a short textbook for postgraduates who have just joined the specialty to have the glimpse of the subject and understand the basic dermatology before venturing for detailed standard textbooks. There is lack of simple but up to date book for undergraduates who are preparing for Postgraduate Entrance Examination. Though market is flooded with a number of books, many of them are not even framed by dermatology specialty individuals and lack correct and appropriate information. This prompted me to write this book to fulfill the needs of students aspiring for entering in postgraduate courses in reputed institutes of India. The material in this book is based on the standard textbooks and latest information from specialty journals. Introduction to MCQs is a unique section in this book to guide the students. The multiple choice questions are taken from a number of sources to sensitize the student to know certain subject areas in this specialty thoroughly and accordingly the book section gives relevant points highlighted for quick revision of facts. The suggestions and healthy critical remarks will be very much appreciated to improve this book. Devinder M Thappa

Acknowledgements I would like to thank those who helped me to update chapters 1. Dr Balaji Adityan for updating • Principles of Diagnosis in Dermatology • Bacterial Infections • Viral Infections • Fungal Infections • Skin Changes in Pregnancy and Old Age 2. Dr Sakthi Kandan for • Infestations • Disorders of Hair and Nails • Metabolic and Nutritional Disorders • Skin in Systemic Diseases 3. Dr Sowmya Kaimal for • Pediatric Dermatology • Human Immunodeficiency Virus Infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS) 4. Dr Amiya Kumar Nath for • Eczema • Connective Tissue Disorders • Genetics and Genodermatoses 5. Dr Abhijit Chougule for • Differential Diagnosis for Leprosy • Treatment of Leprosy 6. Dr Kishan Kumar Agarwal for • Urticaria, Angioedema and Pruritus • Disorders of Sebaceous, Eccrine and Apocrine Glands 7. Dr Nidhi Singh for • Cutaneous Tuberculosis and Atypical Mycobacterial Infections • Vesiculobullous Disorders • Pigmentary Disorders Following residents helped in framing MCQs for postgraduates 1. Dermatology Basics • Dr Abhijit Chougule • Dr Kishan Kumar Agarwal 2. Clinical Dermatology Part -I • Dr Rashmi Kumari

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Essentials in Dermatology • Dr Balaji Adityan • Dr Ajay Kumar Singh • Dr Anuradha Priyadarshini • Dr Tukaram Sori 3. Clinical Dermatology Part -II • Dr Malathi • Dr Sathyamoorthy 4. Sexually Transmitted Diseases • Dr Sowmya Kaimal • Dr Rajalakshmi 5. Leprosy • Dr Abarna Devi • Dr Sakthi Kandan

Reviews “…Most of the dermatology textbooks are too much voluminous for undergraduate students already overburdened with other heavy weight subjects. Not only undergraduates, beginners at the postgraduate level also face problem to acquire basic conception from such large books. So there is always a need for a concise book which can provide clear basic conception and up-to-date knowledge to the students….will be of immense help to the postgraduate entrance examinees….should be collected in all undergraduate medical college libraries for the benefit of the students…” Indian J Dermatol 2003; 48(4): 248. “…The stated aim of the book is to have a short textbook for new entrants to postgraduate studies in dermatology which could glimpse of the subject and understand basic dermatology before venturing for detailed standard textbooks. The second aim stated is to fulfill the needs of students aspiring for entering in postgraduate courses in reputed institutes….well written and fulfill the stated aims…An approach to attempting MCQs appears to be a very useful chapter….strongly recommend this book to the new entrants in specialty training and those preparing for admission to postgraduate courses…” Indian J Dermatol Venereol Leprol 2004; 70(6): 393.

Contents

SECTION 1: DERMATOLOGY 1. Ten Most Influential People in Medicine and Dermatology .................................................... 3 2. History of Dermatology in the World ............................................................................................ 5 3. Microanatomy of the Skin ................................................................................................................ 8 4. Physiology, Biochemistry and Immunology of the Skin ......................................................... 13 5. Principles of Diagnosis in Dermatology ..................................................................................... 16 6. Bacterial Infections .......................................................................................................................... 31 7. Viral Infections ................................................................................................................................. 43 8. Fungal Infections ............................................................................................................................. 57 9. Infestations ........................................................................................................................................ 72 10. Papulosquamous Disorders ........................................................................................................... 82 11. Eczema ................................................................................................................................................ 99 12. Vesiculobullous Disorders ........................................................................................................... 114 13. Cutaneous Tuberculosis and Atypical Mycobacterial Infections ........................................ 127 14. Connective Tissue Disorders (Collagen Vascular Disorders) ............................................... 134 15. Pigmentary Disorders ................................................................................................................... 148 16. Keratinization Disorders .............................................................................................................. 156 17. Urticaria, Angioedema and Pruritus .......................................................................................... 166 18. Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis ................................................................................................. 172 19. Disorders of Sebaceous, Eccrine and Apocrine Glands ......................................................... 180 20. Disorders of Hair and Nails ......................................................................................................... 189 21. Metabolic and Nutritional Disorders ......................................................................................... 198 22. Genetics and Genodermatoses .................................................................................................... 210 23. Skin in Systemic Diseases ............................................................................................................ 222

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Essentials in Dermatology 24. Skin Changes of Pregnancy and Old Age ................................................................................. 237 25. Pediatric Dermatology .................................................................................................................. 240 26. Benign, Pre-malignant and Malignant Tumors of the Skin .................................................. 246 27. Topical Formulary and Key Systemic Drugs ............................................................................ 257 28. Dermatosurgical Procedures ........................................................................................................ 272

SECTION 2: SEXUALLY TRANSMITTED DISEASES AND HIV INFECTION 29. Historical Milestones in Sexually Transmitted Diseases ...................................................... 279 30. History Taking and Examination in Sexually Transmitted Diseases (STDs) .................... 282 31. Sexually Transmitted Diseases ................................................................................................... 288 32. Human Immunodeficiency Virus Infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS) ....................................................................................... 309 33. Antiretroviral Therapy (ART) ..................................................................................................... 318

SECTION 3: LEPROSY 34. Historical Milestones in Leprosy ................................................................................................ 327 35. History Taking and Examination in Leprosy ........................................................................... 330 36. Clinical Leprosy ............................................................................................................................. 333 Multiple Choice Questions .................................................................................................................... 351 Some Useful Medical Mnemonics ....................................................................................................... 441 Terminology ............................................................................................................................................. 447 Answers ..................................................................................................................................................... 465 Index ........................................................................................................................................................... 469

Ten Most Influential People in Medicine and Dermatology

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Ten Most Influential People in Medicine and Dermatology

THE MILLENNIUM AND MEDICINE: THE TEN MOST INFLUENTIAL PERSONS 1. Louis Pasteur (1822-1895): Proposed the “germ theory”. He first associated a specific micro organism (bacillus) with a specific disease (anthrax). He developed the method of pasteurization—a heating process that kills bacteria in milk, wine and other liquids. He was also a pioneer in stereochemistry. 2. Robert Koch (1843-1910): The first to isolate the anthrax bacillus (1876). In 1883, he published a method of preventive inoculation against this disease. In 1882, he announced the discovery of tubercle bacillus and in 1883; he discovered the cause of cholera. He was awarded the nobel prize in physiology or medicine in 1905. 3. Rudolf Virchow (1821-1902): Founded Cellular pathology. His concept that the basis of disease is the cell, the essential functional and structural unit of the body, was of monumental importance as a basis for understanding the cause, the process and the results of the disease. 4. Gregor Mendel (1822-1844): Formulated the laws of heredity. Mendel’s work laid the mathematical foundation of the science of genetics.

5. Francis Crick (1916-) and James Watson (1928): Accredited with determining the molecular structure of DNA, the chemical substrate of heredity, which is regarded as the most important discovery of the 20th century in medicine and science. They were awarded the nobel prize in 1962 sharing it with Maurice Wilkins (1916). Currently, Crick is associated with the Salk Institute for biological studies in San Diego while Watson is the director of the Cold Spring Harbor lab in southeastern New York. 6. Marie Curie (1867-1934): Discovered radioactivity and was given the nobel prize in 1903. The discovery formed the basis of radiation therapy. In 1911, she was again conferred the Nobel Prize in chemistry for her discovery of radium and polonium. 7. Edward Jenner (1749-1823): Introduced the inoculation for smallpox at the end of the 18th century, which is considered one of the greatest triumphs in the history of medicine. 8. Karl Landsteiner (1868-1943): Called the “father of blood grouping” - a concept without which blood transfusion would not be possible. In 1901, he showed that there are at least three major types of blood. Landsteiner was awarded the noble prize for his work in 1930.

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Essentials in Dermatology 9. Wilhelm Rontgen (1845-1923): Discoverer of X-rays in 1895 and nobel prize winner in Physics in 1901. The value of X-rays in the diagnosis and treatment was recognised and accepted almost from the outset of their discovery. 10. Sigmund Freud (1856-1939): Considered the founder of psychoanalysis, he believed that a complex of repressed and forgotten expressions underlies all abnormal mental states and that infantile mental processes are important in later development.

TEN MOST INFLUENTIAL PERSONS IN DERMATOLOGY, VENEREOLOGY AND LEPROSY: INDIA 1. Dr. JS Pasricha: Pioneer of pulse therapy in pemphigus, contact dermatitis in India. 2. Dr. LK Bhutani: Clinical dermatology, “Bhutani’s Colour Atlas of Dermatology”, photobiology. 3. Dr. Dharmendra: “Father of leprosy” in India. 4. Dr. RV Rajam and Dr. PN Rangaiah: Monograph on donovanosis. 5. Dr. VN Sehgal: For his literary contribution in dermatology, venereology and leprosy. 6. Dr. Patrick Yesudian: Clinician par excellence, known for “Patrick Yesudian sign” for palmar freckling in neurofibromatosis type 1. 7. Dr. KC Kandhari: Established department of dermatology at AIIMS. 8. Dr. Gurmohan Singh: contribution to Indian and community dermatology. 9. Dr. Surinder Kaur: Established department of dermatology at PGIMER, Chandigarh. 10. Dr. Sardarilal: First editor of Indian Journal of sexually transmitted diseases, and for contributions in donovanosis.

TEN MOST INFLUENTIAL PERSONS IN DERMATOLOGY, VENEREOLOGY AND LEPROSY: WORLD 1. Dr. Ferdinand Ritter von Hebra– Founder of the new Vienna school of dermatology, which set the basis for modern dermatology. 2. Dr. Robert Willan– Founder of dermatology as a medical specialty. 3. Dr. Josef Jadassohn– Best remembered for his handbook of skin and venereal disease (41 volumes), pioneer in allergology, introduced patch testing. 4. Dr. Johnathan Hunter– Natural history of syphilis, role of inflammation in healing. 5. Dr. Paul Ehrlich– Developed salvarsan (magic bullet) as a treatment for syphilis, was the first to stain tubercle bacilli. 6. Dr. Thomas Bernard Fitzpatrick– Proved that melanin was produced in melanosomes, first editor of Dermatology in General Medicine (1965). 7. Dr. Arthur Rook (1918-1991), Dr. Darrell Sheldon Wilkinson and zoologist John Ebling (1918-1992): Produced their major work, Textbook of Dermatology (alias The Rook Book) in 1968. 8. Dr. Paul Gerson Unna, Dr. HKB Pinkus, Dr. A Bernard Ackerman, and Walter F. Lever: Contributions to dermatopathology. 9. Heinrich Koebner– Koebner phenomenon, founder of the dermatology clinic at the University of Breslau. 10. GHA Hansen– Identified M. leprae as the causative agent of leprosy in 1873.

History of Dermatology in the World

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History of Dermatology in the World

HISTORY OF DERMATOLOGY IN THE WORLD • In Greek and Roman era, Hippocrates recognized and described many diseases. Some of the medical facts he observed are as true today as they were over 2000 years ago. He rescued medicine from magic and superstition, therefore rightly so called “the Father of Medicine”. • Dermatology, the science of the skin, was one of the many specialties, which evolved from general internal medicine during the course of the nineteenth century. Most diseases of skin, as ‘external diseases’, had for many centuries fallen within the province of the surgeon or of the quack. • Until the eighteenth century was welladvanced, physicians with few exceptions were little concerned with the skin, apart from the exanthematic eruptions of acute fevers. However, during the last decades of that century, many of the great physicians recorded their observations on diseases of the skin. The solid contributions of some, such as Heberden and Cullen, which have received too little attention from the historians of dermatology, laid the foundations on which the pioneer specialist

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dermatologists of the following century were able to build. Despite developments in 19th centuryvaccination against small pox, recognition of cellular pathology, Louis Pasteur’s germ theory of infection, development of anaesthesia and microscope, the treatment of most skin diseases was at best symptomatic and at worst dangerous. Amongst the first to specialize in dermatology was Ferdinand Hebra (18161880) in Vienna, who led the torch of dermatology, others followed him. The last half of 19th century saw dermatology and venereology emerge as a specialty in its own right. The 20th century brought a wealth of new scientific knowledge that can be used to help the sick. Perhaps, the most important single discovery was that of Sir Alexander Fleming, the British bacteriologist who found the first antibiotic, penicillin. During 20th century, certain turning points occurred in general sociocultural factors (welfare—public health, vaccines, hygiene, clean water, sewerage, etc; war; communications–books, photography, radio, films, television, computers; transport), general scientific developments (genetics- structure

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Essentials in Dermatology of DNA; inflammation-histamine, prostaglandins, cytokines, adhesion molecules; immunology-cell mediated and humoral immunity; tissue culture; pathogenic agentsspirochetes, viruses, prion; therapies- x-rays, antibacterial, immunosuppressive; controlled clinical trials), and strictly dermatological areas(books- Jadassohn, Pillsbury, Rothman, Rook; biologykeratinocyte, melanocyte, Langerhans cell, basement membrane; diseases- epidermolysis bullosa, pemphigus, toxic epidermal necrolysis; people- from Unna to Katz; therapies- local steroids, griseofulvin, phototherapy, retinoids, Moh’s surgery, laser, cryotherapy).

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EVOLUTION OF DERMATOLOGY • In India, recognition of dermatology as a specialty distinct from internal medicine is recent; it has still not grown to its full stature in practice and teaching. • Therapeutics of dermatoses have been known and practiced by our ancient physicians for centuries. Charaka Samhita contains one chapter on the subject. • Medical charlatans selling panaceas for cutaneous ailments and faith healers were commonly seen all over the country. With the advent of scientific dermatology, their number and importance has dwindled. • In the latter part of the 19th century, the health authorities in then British India became aware of the need to have data on prevalence of dermatoses and venereal diseases. • The first chair of dermatology was established at Grant Medical College, Jamshedji Jeejebhoy Hospital (JJ Hospital), Bombay in 1895. • The second department, at the School of Tropical Medicine in Calcutta, was started in 1923, after a gap of nearly 28 years, under

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the patronage of Dr Ganpati Panja and Colonel Acton. During the period from 1956 to 1974, the status of the specialty was further elevated and steps were taken by state governments to set up departments of dermatology and venereology in medical institutions. Dr UB Narayan Rao, a pioneer in the specialty, gets the credit for the creation of an association of dermatologists and venereologists in Bombay (July 1, 1947), and for Indian Journal of Venereology started in 1935, renamed as Indian Journal of Venereal Diseases and Dermatology in 1940, and later renamed as Indian Journal of Dermatology and Venereology in 1955, the first issue of which was edited by him. In 1962, it was decided to affiliate the association of dermatologists and venereologists with Association of Physicians of India (API). This continued until 1974, after which this affiliation was severed and association became an independent body. On January 28, 1973, the present association the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) came into existence. Since 1976 the bimonthly journal is being published under the title Indian journal of dermatology, venereology and leprology.

EVOLUTION OF VENEREOLOGY • Syphilis was first introduced into North India nearly 500 years ago. • National STD Control Programme was started in 1946. This programme continued to operate till 1991 and with the arrival of HIV infection in the country, the programme was

History of Dermatology in the World

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brought under the purview of National AIDS Control Organization (NACO) in the year 1992. The monograph by Rajam and Rangiah on donovanosis (granuloma inguinale, granuloma venereum) is testimony to the teaching and research standards set by these two giants at institute of venereology, Chennai. Dr. CN Sowmini founded the Indian Association for the study of sexually transmitted diseases (IASSTD) in the year 1975. In the year 1980, this specialty, under the banner of IASSTD, started its own exclusive journal, the Indian Journal of Sexually Transmitted Diseases. The late Dr. Sardarilal was its founder editor and guiding force, who had already made a mark in the field of research, especially in donovanosis. Somehow venereology did not prosper as much, even though it led in front of dermatology and leprology in teaching and in the starting of its own journal in early part of 19th century. Unlike in the West, venereology in India has been combined with dermatology in most of the universities.

EVOLUTION OF LEPROLOGY • There is a great deal of speculation about the early history of leprosy. The earliest records, which give accurate descriptions of the disease, come from India and may have been written as early as 600 BC.

• In Sushrata Samhita (600 BC), one finds a reasonably good account of the clinical features and treatment of the disease. Sushrata described the different forms of leprosy, and these forms fit in fairly well with the forms of the disease as recognized at the present time. • Sushrata described the treatment of the disease with Chaulmoogra oil (hydnocarpus oil), which till 1940s was the mainstay in the treatment of the disease. • The first known asylum for leprosy patients was established in Calcutta early in the 19th century, followed by another in Varanasi. • “Leprosy in India”, a journal specific for leprosy, was started by Dr. Ernest Muir in 1929, initially in the form of quarterly notes, and later on transformed itself to a fullfledged scientific journal. Consistent with its contents and nature, Leprosy in India was renamed as the Indian Journal of Leprosy in 1984. • Dr. Dharmendra straddled the scene of leprosy in India like a giant and is known for lepromin test, Indian classification of types of leprosy and the journal “Leprosy in India”. • The National Leprosy Control Programme (NLCP) was started in 1954-55. In view of scientific advancement and availability of highly effective treatment of leprosy, the programme was redesignated as National Leprosy Eradication Programme (NLEP) in 1983. • In 1991, the World Health Organization set a target of elimination of leprosy as a public health problem by the year 2000. India achieved this target in 2005.

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Essentials in Dermatology

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Microanatomy of the Skin

Dermatology may be defined as the study of the skin and its diseases or is a branch of medical science, which deals with systematic study of skin in health and disease. Since skin conditions constitute 10 to 30% of outpatient attendance in any hospital, they are often easily noticed by others (hence a cause of great social concern to the patient) and very often, skin diseases offer diagnostic clue to many major systemic disorders, makes this subject challenging and important to study.

FUNCTIONS OF THE SKIN The skin is the largest organ of the body, accounting for 16-20% of total body weight. The skin of an average adult covers an area just under 2 m2. It not only gives shape to the body but also helps it in many ways – the important functions of the skin are: 1. Protection (Barrier function) from: a. Physical injuries b. Chemical injuries c. Infections 2. Thermoregulation 3. Sense organ: A number of sensations – touch, pressure, warmth, cold and pain are perceived by the skin. 4. Storage of electrolytes, carbohydrates, water, fat, vitamins, proteins, etc.

5. Vitamin D formation: Vitamin D 3 is essential for skeletal development. 6. Absorption: The skin surface also performs absorptive function and is the basis of topical therapy in dermatology. 7. Excretion: Some of the toxins may be excreted through the skin. 8. Immune surveillance: This immunological function is performed by Langerhan’s cells, dendritic cells (intermediate) and keratinocytes. 9. Mechanical function: The mechanical properties of the skin depend mainly on the dermis. 10. Cosmetic function: Colour of the skin and hair and nails are important for their decorative value. Hair does not perform a “vital” physiologic function but it does provide a sexually attractive ornament.

DEVELOPMENT OF SKIN Epidermis develops from ectoderm lateral to neural crest, dermis from mesenchyme and neural crest cell, subcutaneous fat from mesenchyme and melanocytes from neural crest. Foetal skin development occurs in three stagesspecification, morphogenesis and differentiation. Its specification occurs from 0 to 60 days, morphogenesis from 2 to 5 months, and differentiation from 5 to 9 months.

Microanatomy of the Skin

STRUCTURE OF THE SKIN Skin has 3 layers (Fig. 3.1) 1. Epidermis 2. Dermis 3. Subcutaneous fat (Hypodermis).

Epidermis It is approximately 0.4 mm to 1.6 mm in thickness. The majority of the cells in the epidermis are the keratinocytes. These cells are organized into five layers-stratum corneum, stratum lucidum (present only in palmar and plantar skin), stratum granulosum, stratum spinosum, and stratum basale or stratum germinatum (Fig. 3.2). Stratum corneum is the outermost layer containing flattened anucleated cells without cell organelles. The thick epidermis of palms and soles has an additional layer underneath the stratum corneum that is electron lucent and is called the stratum lucidum. The stratum granulosum is so called due to the presence of

intracellular basophilic keratohyaline granules and consists of 2-5 cells layer. The stratum spinosum contains 8-10 layers of polyhedral cells with round nuclei. The stratum basale or stratum germinativum consists of single layer of cuboidal or columnar cells. Keratin filaments are a hallmark of the keratinocytes and the process by which a keratinocyte of the basal layer ultimately changes into keratin is known as keratinization and it usually takes 4 weeks for its completion. The epidermal turnover time is about I month. The other member cells found in the epidermis are melanocytes (derived from neural crest, produce melanin), Langerhans cells (origin from bone marrow, play important role in cutaneous immune mechanisms), and Merkel cells (slow adapting type 1 mechanoreceptors).

The Dermal-epidermal Junction The dermal-epidermal junction (DEJ) is a basement membrane zone (BMZ) that welds the epidermis to underlying dermis.

Fig. 3.1: Structure of the skin

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Essentials in Dermatology

Fig. 3.2: Diagrammatic representation of shapes of various cells in the epidermis and changes in them as they move up from basal cell layer to stratum corneum during the process of keratinization

The dermal-epidermal junction is undulated, forming dermal papillae (upward projections of the dermis into the epidermis) and rete ridges (downward projections of epidermis into the dermis). The DEJ under electron microscope consists of four components- plasma membrane of basal keratinocytes with hemidesmosomes, lamina lucida (made up of anchoring filaments and laminin 5), lamina densa ( has type IV collagen and laminin 5), and lamina fibroreticularis (containing anchoring fibrils, dermal microfibrils, and collagen fibers). This DEJ is weakest at lamina lucida.

Dermis The dermis is formed by connective tissue having fibres (collagen, elastic and reticulin) and

ground substance (made up of proteoglycans and glycosaminoglycans). It varies in thickness from about 1 mm on the face to 4 mm on the back and thigh. Collagen fibres are the major component of the dermis, accounting for 75% of dry weight of the skin. Approximately 80-90% of collagen fibres in the dermis are of type I collagen. They are responsible for the mechanical properties of the dermis. Elastic fibers constitute approximately 4% of dry weight of dermal matrix proteins. Due to their elasticity, they maintain the normal configuration of the skin. The dermis can be divided into an upperpapillary dermis that interdigitates between the rete ridges and the deeper-reticular dermis recognized by the thicker, aggregated bundles of collagen.

Microanatomy of the Skin

Epidermal Appendages Like a. Pilosebaceous unit b. Sweat glands. Pilosebaceous unit: It consists of a hair follicle containing hair and sebaceous glands opening into follicular canal of hair follicle. Sebaceous glands are lipid secreting holocrine glands. Their maximum density is in seborrhoeic areas of the body, i.e. scalp, face, upper chest, etc. They get activated at puberty under the influence of androgen hormone. Functions of sebum are: 1. Barrier function by preventing loss of water from the skin 2. Emulsification of surface eccrine sweat 3. May have mosquito repellant action 4. Protection against sunburn 5. Has a vitamin D precursor. Hair structurally consists of a cuticle, cortex and medulla. These keratinous fibres are of two types in adults-terminal hair and vellus hair. Hair grows at the rate of 0.3 mm per day and they undergo growth cycle. These recurring cycles consist of anagen (active growth phase), catagen (static growth phase) and telogen (shedding phase) phases. On the scalp, 80% to 85% of hair are in anagen phase and 15% to 20% in catagen and telogen phase. The anagen phase lasts for two to five years, a short catagen of few days and a telogen phase of three months. Functions of hair are: 1. Cosmetic 2. Hair screens entry of irritants to nose 3. Protect scalp from sunrays 4. Shields the eyes 5. Helps in perception of tactile stimuli. Sweat glands: Two types of sweat glands are eccrine and apocrine sweat glands. Eccrine sweat glands: They are tubular structures, which open on to the skin directly and have three segments–the secretory coil (consists of single layer of secretory cells–clear and dark

cells) in the deep dermis, straight intradermal (has two layers of cuboidal cells lined by eosinophilic cuticle on luminal side) part and coiled or spiral intraepidermal (consists of an inner layer of luminal cells and two to three outer layer of epithelial cells) part. Sweat glands are most abundant on the palms, soles, forehead and axillae. These glands are highly developed and responsive part of the thermoregulatory apparatus, innervated by cholinergic nerve fibers. Functions of sweat are: 1. Sweating in heat stress 2. Excretion of heavy metals and drugs. Apocrine sweat glands: These tubular glands consists of two main parts – the coiled secretary gland (consists of single layer of cuboidal or columnar cells, surrounded by a layer of myoepithelial cells) and the straight excretory duct (consists of double layer of cuboidal cells and inner eosinophilic cuticle) which opens into follicular canal just above the openings of sebaceous glands. They are distributed along the mammary line, i.e. axillae, areolae, periumbilical area, mons pubis, genital and perianal areas. Apocrine gland secretion in man serves no function. Pheromones–its role in humans is debated. Nail unit: It is yet another epidermal appendage. It consists of nail matrix just underneath the proximal nail fold which gives rise to nail plate – a keratinized structure. The distal portion of the nail matrix is visible usually in thumbnail as white crescent or half moon known as lunula. The rectangular nail plate rests on a nail bed and is bounded on two sides by lateral nail folds. The cuticle seals the space between nail folds and nail plate. The distal portion of nail juts out as a free end. The space underneath the free end of the nail plate is called subunguium. In contrast to hair, nail is a continuously growing structure, usually at a rate of 0.1 mm per day.

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Essentials in Dermatology Functions of nails are: 1. Protect terminal phalanges 2. Cosmetic function 3. Helps in appreciation of tactile stimuli 4. Scratching of skin 5. Helps in holding minute objects with finger tips. Besides the above elements, dermis contains blood vessels which form two plexuses (other than providing nutrition to the skin, blood vessels regulate temperature and blood pressure), lymphatics roughly parallel the major vascular plexuses, nerves of the skin are part of two major systems – somatic sensory and autonomic motor, smooth muscle occurs in the skin as arrectores pilorum, as the tunica dartos of the scrotum and in the areolar around the

nipples and cells – mast cells, fibroblasts, monocytes, macrophages, dendrocytes and pericytes, etc.

Subcutaneous Fat (Hypodermis) The subcutaneous fat layer is constituted by adipocytes. It is abundant over the breasts, buttocks, and abdomen, thinner over the nose and sternum and absent over the eyelids and male genitalia. It acts as shock absorber, helps in heat production and hormone conversion, facilitate mobility of skin over structures that underlie and acts as an insulator for heat. A cosmetic role is contributed by the accentuated distribution of fat in some sites in the sexes. Most importantly, it stores triglycerides, which serves as fuel for energy.

Physiology, Biochemistry and Immunology of the Skin

4

Physiology, Biochemistry and Immunology of the Skin

Main functions of the skin are protection, thermoregulation, sensory, storage organ, vitamin D formation, absorption, excretion, immune surveillance, mechanical and cosmetic function. Some important physiological, biochemical, and immunological processes of the skin are summarized below.

epidermal barrier is localized to the stratum corneum. The skin has two barriers to UV radiations: a melanin barrier in the epidermis; and a protein barrier concentrated in the stratum corneum. Both function by absorbing radiation thereby minimizing absorption by DNA and other cellular constituents.

PROTECTIVE FUNCTIONS OF THE SKIN The innermost region of human skin is the subcutaneous fat layer. This layer insulates reduces heat movement into or out of the body, absorbs energy from blunt mechanical trauma and is active in general energy metabolism. Superficial to the fat layer lies the dermis, composed of collgen-glycosaminoglycan complexes which also protects the body from blunt mechanical trauma. Overlying the dermis is the epidermis which consists of several stratifying layers of nucleated keratinocytes and anucleated top layer, the stratum corneum which performs the major barrier function. The skin acts as a two way barrier to prevent the inward or outward passage of water and electrolytes. The physical barrier is largely situated in the epidermis, isolated epidermis being as impermeable as whole skin, whereas once the epidermis is removed, the residual dermis is almost completely permeable. The

PERCUTANEOUS ABSORPTION The skin is considered to be a composite membrane with three anatomically distinct layers; the stratum corneum (10 µm), the viable epidermis (100 µm), and the uppermost papillary layer of the dermis (100-200 µm), each having a different diffusion constant. Even healthy adult human skin allows some permeation of almost every substance, and rates of penetration of different materials may differ by 10,000 fold. The efficiency of the barrier differs between body sites. The scrotum is particularly permeable and the face, forehead, and dorsa of the hands may be more permeable to water than the trunk, arms, and legs. The palms are particularly impermeable to nearly all molecules except water. The barrier is affected by many other factors, such as age, environmental conditions and physical trauma, and permeability can be

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Essentials in Dermatology enhanced by various agents, permitting increased access of topically applied drugs.

KERATINIZATION Keratinization is a process of differentiation of germinative cells in the basal cell layer into the deceased cornified cells of stratum corneum. It involves: 1. Synthesis of distinctive proteins (e.g. keratins, filaggrins, and involucrin) and lamellar granules, and 2. Alterations of nuclei, cytoplasmic organelles, plasma membranes and desmosomes. Keratin function is to provide mechanical strength, cellular structure, and assistance in adhesion molecule attachment. “Soft” keratin desquamates as the result of enzymatic action but the “hard” keratin of the hair and nails does not, thus requiring periodic cutting. The epidermis is the prototype of keratinizing squamous epithelia, also present in the oesophagus, vagina and oral mucosa.

MELANOCYTES AND MELANOGENESIS Melanocytes are pigment forming cells in the epidermis. Each melanocyte supplies pigment, melanin to approximately 36 keratinocytes and thus form epidermal melanin unit. Two types of melanin are synthesized by melanocytes, eumelanins and pheomelanins. Melanin is synthesized from tyrosine under the influence of enzyme tyrosinase through the formation of various intermediates (dihydroxyphenylalanine [dopa], dopaquinone, leucodopachrome, dopachrome, 5’ 6’ dihydroxyindole, indole 5’ 6’-quinone, melanochrome).

FUNCTIONS OF THE MELANIN 1. Protect the skin from harmful effects of sunlight by scattering and absorbing ultraviolet light.

2. Melanin may also act as a biochemical neutralizer of toxic free radical oxygen derivatives, byproducts of various inflammatory processes. 3. Melanocytes situated in the matrix of anagen follicles impart to hair various colours, e.g. blond, brunette and red head.

THERMOREGULATION The maintenance of a near constant body core temperature of 37oC is a great advantage to humans, allowing a constancy to biochemical reactions which would otherwise fluctuate widely with temperature changes. The thermoreceptor cells of the skin are distributed irregularly over the skin, there being warm- and cold-sensitive thermoreceptors. Information on changes in their stimulation in response to changes in the temperature is sent to the hypothalamus leading to either to inhibition of sweating or stimulation of shivering. Skin temperature has a greater role in mediating the behavior, for example by turning on the heating or putting on extra clothing. Thermoregulation depends on several factors, including metabolism and exercise but the skin plays an important part in control through the evaporation of sweat and by direct heat loss from the surface. Heat can be lost through the skin surface in four ways: 1. Radiation 2. Convection 3. Conduction 4. Evaporation

SKIN FAILURE Skin failure is defined as a loss of normal temperature control with inability to maintain the core temperature, failure to prevent percutaneous loss of fluids, electrolytes and proteins with resulting imbalance and failure of

Physiology, Biochemistry and Immunology of the Skin mechanical barrier to penetration of foreign materials. Apart from thermal burns, skin failure can occur as a consequence of a number of dermatological diseases including Stevens Johnson syndrome, toxic epidermal necrolysis, pustular psoriasis and erythroderma of various causes.

COLLAGEN IN THE DERMIS The closely related proteins of collagen family are the main fibrillary components of the connective tissues and the major extracellular proteins of the human body. The physiological role of collagen fibers in the skin is to provide tensile properties that allow the skin to serve as a protective organ against external trauma. Collagen is the major structural protein constituting 70% to 80% of dry weight of the dermis. The main aminoacids in collagen are glycine, proline and hydroxyproline.

Elastic Fibers in the Dermis Elastic fibers of the connective tissue form a network responsible for the resilient properties of the skin. In sun protected human skin, elastin content is about 1% to 2% of the total dry weight of dermis. Ground Substance in the Dermis The ground substance of skin is largely made up of glycosaminoglycans(GAG) and provide viscosity and hydration in the dermis. Three

types of GAG are chondroitin sulphate, dermatan sulphate and hyaluronic acid.

IMMUNOLOGICAL COMPONENTS OF SKIN The immunological functions of the skin depend both upon cells in the epidermis and on dermal cellular constituents. Antimicrobial peptides (AMPs) are a diverse group of proteins that are involved as first line of immune defense by many living things. In human skin, AMPs provide a chemical barrier to potentially pathogenic microorganisms. Sebaceous lipids have been reported to possess antibacterial properties and glycophospholipids and free fatty acids of stratum corneum have bacteriostatic effect selective for pathogenic organisms. Skin associated lymphoid tissue (SALT) is langerhans cells, T lymphocytes, mast cells and keratinocytes. They are involved in various hypersensitivity reactions of the skin. Hypersensitivity is defined as inappropriate or exaggerated immune response to a foreign or self antigen resulting in tissue damage. Main types of hypersensitivity responses of skin are type I (immediate), type II (antibody-dependent cytotoxicity), type III (immune complex disease) and type IV(cell mediated or delayed). Urticaria and anaphylaxis is the example for type I hypersensitivity, transfusion reactions for type II hypersensitivity, leukocytoclastic vasculitis for type III hypersensitivity and allergic contact dermatitis for type IV hypersensitivity.

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Essentials in Dermatology

5

Principles of Diagnosis in Dermatology

Dermatologists often prefer to examine the patient before obtaining the history and review of systems. This approach is preferred because diagnostic accuracy is higher when visual examination is approached without preconceived ideas. Moreover, some dermatologic lesions are so distinctive that history is not required to make a diagnosis. A practical and convenient way to arrive at a diagnosis may be...

Chief complaints: Limit them to just three only History of present illness: “What is your skin problem?” This allows patient to point out the lesions and the area involved. Three basic questions. 1. Onset and evolution. 2. Symptoms. 3. Treatment taken. Onset and evolution: To determine the duration of the disorder, how it evolved over time, initial site of the disease, mode of spread.

PRELIMINARY GENERAL HISTORY

Symptoms: Itching is the most common and most important symptom in dermatology. Intense itching, e.g. scabies, atopic dermatitis, lichen planus, dermatitis herpetiformis. Pain may predominate in herpes zoster, furuncles, etc. Loss of sensation points towards leprosy, or follicular mucinosis. Allodynia (production of pain by trivial stimuli) occurs in postherpetic neuralgia. Reversal of hot and cold sensation may be due to ciguatera fish poisoning. They may be just asymptomatic as in molluscum contagiosum, basal cell carcinoma, etc.

Biodata: Age, sex, income, occupation, address, marital status.

Treatment history: Skin lesions are often selfmanipulated by home remedies, or over the

Principles of Diagnosis in Dermatology counter medication, since they are easily accessible, and since disease is of chronic nature. Full detailed history of medication used should be known because 1. Disease may be caused or aggravated by medication- Fixed drug eruption, dermatitis medicamentosa. 2. Patient may have already used the drug without desired outcome, we planned to give. Avoid potential embarrassment when the patient says “I have already tried that and it didn’t work”. Detailed follow-up history: This history is taken after some diagnosis or conclusion was reached by initial history and examination, and this includes. • Past history. • Family history. • Review of systems. • Social history. • Females- menstrual/obstetric history. Past history: a. History of same disease before. b. History of prolonged illness– diabetes, hypertension. c. Drugs used for other problems (drug rash, urticaria). d. Drug allergies– avoid prescribing those drugs. e. Atopic history– asthma, hay fever, eczema. Family history: It is important for diagnosis, prognosis, treatment and genetic counseling. Family history important in: a. Infectious disorders – scabies b. Inherited disorders – atopy, psoriasis. c. Genodermatoses. Review of other systems: It is required in multisystem disorders like SLE, scleroderma, or lepromatous leprosy. Social history: Encounter with potentially sensitizing materials e.g., in patients with

industrial dermatosis, contact dermatitis. Stress and strain at work may lead to exacerbation of psoriasis, neurodermatitis, etc. Habits: Alcohol induces porphyria cutanea tarda in predisposed, influences the severity and therapeutic options in psoriasis. Smoking may be aggravating factor in palmoplantar pustulosis.

PHYSICAL EXAMINATION It has been said by Goethe “What is most difficult of all? It is what appears most simple: To see with your eyes what lies in front of your eyes” .

Requirements for the Skin to be Properly Examined Three essential requirements 1. Preferably a completely undressed patient, clothed only in an examination gown. If not possible, at least, the affected part should be properly exposed. 2. Adequate illumination: Preferably sunlight or a bright overhead fluorescent lighting. Penlight is used in side lighting- to determine if a lesion is subtly elevated and for examining the oral cavity. 3. An examining physician ready to see what is before him. A complete cutaneous examination should be made, this includes examining— • Skin from head to foot. • Mucous membrane in mouth and genitals • Hair and nails. The examination includes inspection and palpation, besides percussion and auscultation. Palpation is useful in— • Assessing the texture and consistency. • Evaluate whether a lesion is tender or not. • Reassure a patient that they do not have a contagious disease.

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Essentials in Dermatology Hand lens useful on occasions like identifying: a. Altered skin markings in tumors. b. Nail fold telangiectasia. c. Burrows in scabies. d. Wickham‘s striae- for this place a drop of mineral oil on the area, which makes the stratum corneum transparent. Subtle genital warts- ‘aceto-whitening’, gauze soaked with 5% acetic acid applied in suspected area for 3 minutes, warts turn white. Actually individual skin lesions are analogous to the letters of the alphabet, and groups of lesions can be analogous to words or phrases. Basis of morphological lesions is given in the form of table for clear understanding. Basis of morphological lesions in dermatology 1. Impalpable change- Macule 2. Palpable change• Solid change-Papule, plaque, nodule, wheal • Superficial visualized free fluid collectionVesicle, bulla • Superficial free pus collection-Pustule, abscess • Deep free fluid/semisolid material collection-Cyst 3. Loss of skin-Erosion, ulcer 4. Healing stage- Scale, crust 5. End stage- Atrophy, scar

Fig. 5.1: Macule—depigmented flat lesions of variable size and shape of vitiligo vulgaris and lip tip type

Ultimately, diagnosis may rest on recognition of lesions and their distribution and arrangement, whether they are primary, secondary or some special lesions. Describe their shape, size, color and distribution. Take the help of diagnostic tools for further details.

Primary Lesions These are the lesions, which appear first in any skin disease. They are the best clues to the diagnosis. They are: • Macule: The macule is a discrete, flat, circumscribed lesion that differs from surrounding skin because of its color (Fig. 5.1). It may be a small or a large macule. Earlier used term “patch” is now obsolete. Macule may be erythematous, hypo-

Fig. 5.2: Papule—solid elevated lesions of verruca vulgaris of less than 0.5 cm

pigmented, hyperpigmented or of any other color. • Papule: It is a discrete, circumscribed, solid elevated lesion of less than 0.5 cm in size (Figs 5.2 to 5.5). So, it is a palpable lesion. A papule may be dome shaped, verrucous, umbilicated, pedunculated, etc.

Principles of Diagnosis in Dermatology

Fig. 5.3: Papule—dome shaped papule, a few of them umbilicated of molluscum contagiosum

Fig. 5.5 Violaceous colored papules of lichen planus over the genitalia and thigh

Fig. 5.4: Typical umbilicated papule of molluscum contagiosum

Fig. 5.6: Plaque—flat elevated lesions covered with silvery white micaceous scales of psoriasis vulgaris

• Plaque: A plaque is a circumscribed solid raised lesion with a flat top. It is formed due to coalescence of papules (Figs 5.6 and 5.7). It may be a lichenified plaque, eczematous plaque, psoriasiform plaque, flat smooth plaque, etc. • Nodule: A nodule is a discrete circumscribed solid elevated lesion, which is more felt than

seen from the top (Figs 5.8 and 5.9). It may develop from a papule. • Vesicles and bullae: Vesicle and bullae are two terms used for circumscribed elevated lesions containing free clear fluid, called blister. If it is less than 0.5 cm, it is called vesicle (Fig. 5.10) and if more than this, it is a bulla (Figs 5.11 and 5.12). They may be tense or flaccid.

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Fig. 5.7: Large well-defined erythematous plaques of psoriasis vulgaris

Fig. 5.8: Nodule—solid deep-seated elevated lesion due to secondaries in the skin

Fig. 5.9: Erythematous tender nodules of furuncle over the face and neck

Fig. 5.10: Vesicle—cluster of tiny blisters of herpes labialis over the lips

Fig. 5.11: Bulla—small blisters on erythematous bases of bullous pemphigoid

Fig. 5.12: Large tense bulla of bullous pemphigoid on an erythematous base

Principles of Diagnosis in Dermatology • Pustule: A pustule is a circumscribed elevated lesion containing visible pus (Fig. 5.13). It results from an epidermal or upper dermal accumulation of pus. • Cyst: A cyst is a sac that contains liquid or semisolid material. • Wheal: Wheal is a pale or erythematous edematous, transient, evanescent lesion. • Diffuse thickening of skin: It may result from edema of dermis (pitting edema or nonpitting edema) or infiltration of dermis (e.g. myxoedema, lepromatous leprosy).

Secondary or Consecutive Lesions They are due to the subsequent changes, which takes place on the primary lesions, either as a part of natural evolution or due to manipulation of the patient. • Oozing: It is due to the rupture of vesicles or bullae. • Crust: It is dried up exudate like serum, pus or blood (Fig. 5.14). It may be thick or thin, friable or adherent. It occurs in many inflammatory and infectious diseases. • Scale: Scales are thin, dry plates of heaped up desquamating epithelial cells formed as

Fig. 5.13: Pustule—numerous tiny pus filled lesions on erythematous background in a case of pustular psoriasis

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a result of either increased or abnormal keratinization (Fig. 5.15). Excoriation: An excoriation is a superficial erosion or ulcer caused by scratching. So, it will be linear or have a geometric outline (Fig. 5.16). Erosion: It is a superficial ulceration involving epidermis only which heals without scarring (Fig. 5.17). Ulcer: It is a break in continuity of epithelium, which involves epidermis, and dermis of the skin (Fig. 5.18). It has length, breadth as well as depth. It heals with scar formation. Fissure: Fissure is a linear crack in the skin, which may be superficial or deep to the dermis. Lichenification: It is characterized by thickening of the skin (becomes leather like) with increased skin markings and pigmentation. It is seen in chronic dermatitis. Scar: A scar is an evidence of destruction of the skin with fibrotic tissue replacement. It occurs wherever ulceration has taken place and reflects the pattern of healing in those areas.

Fig. 5.14: Crust—dried out oozed material over the face in impetigo contagiosa

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Fig. 5.15: Scale—face and trunk covered with moist scales of pemphigus foliaceous

Fig. 5.16: Excoriation—multiple linear scratch marks due to itching over psoriatic plaques

Fig. 5.17: Erosion—multiple superficial eroded areas in herpes genitalis

Fig. 5.18: Ulcer—single, painless, indurated ulceration of extragenital primary chancre

• Pigmentation: Pigmentation may be hyper, hypo- or depigmentation of the skin (varies according to the quantity of melanin). • Atrophy: Atrophy refers to a diminution in the size of a cell, tissue, organ or part of the body. The skin becomes thin, shiny and

wrinkled. Atrophy may be of epidermal, dermal or subcutaneous fat. • Sclerosis: Sclerosis means a circumscribed or diffuse hardening or induration in the skin. It occurs as a result of an increase in the amount of dermal collagen, expansion of the

Principles of Diagnosis in Dermatology collagen by ground substance material or altered quality of collagen.

Special Lesions These lesions are given below: • Comedone: It is a plug of keratin and sebum formed in the follicular canal of pilosebaceous unit. Comedones may be closed or open. • Burrows: These are serpentine caves of scabies mite at the level of stratum granulosum. They are visible as S-shaped brownish-black lesions, which at their distal end have a papule housing the mite. • Alopecia means loss of hair. • Telangiectasia: It refers to individually visible dilated vessels. • Poikiloderma: It is a combination of atrophy, pigmentation and telangiectasia. • Purpura: It is visible extravasated blood (Fig. 5.19). It may occur as tiny pinpoint spots

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(petechiae) or larger spots (ecchymoses). The term hematoma refers to an area of massive bleeding into the skin and underlying tissues. “Pinch purpura” hemorrhage induced by mild often subclinical trauma is a characteristic presentation of primary systemic amyloidosis of the skin. Similar periorbital hemorrhage following proctoscopy or pulmonary function testing, postproctoscopic purpura also typifies the vascular fragility induced by systemic amyloidosis. Livedo: Blue red discoloration of the skin of skin due to passive congestion of the vessels often with net-like pattern Exanthem: Abrupt appearance of diffuse or generalized similar skin lesions (usually represents viral infections or drug reactions) Enanthem: Abrupt appearance of mucosal lesions similar to exanthems. Nits: They are glistening white ovoid bodies attached to shafts of hair.

Fig. 5.19: Purpura—multiple, small, erythematous non-blanchable lesions of purpura

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DISTRIBUTION OF SKIN LESIONS IN SOME DERMATOLOGICAL DISORDERS Disease 1. Acne vulgaris 2. Atopic dermatitis 3. Dermatitis herpetiformis 4. Lichen planus 5. Neurodermatitis 6. Pityriasis rosea 7. Psoriasis vulgaris 8. Scabies

9. Seborrhoeic dermatitis

10. Tinea versicolor

Classical sites of involvement Face, upper trunk, proximal parts of upper extremities Infants -face and extensor aspects of limbs (Figs 5.20A and B) Children and adults-flexures (Figs 5.21A and B). Scalp, extensor aspects of limbs, shoulder and buttocks (Figs 5.22A and B). Flexor aspect of upper extremities (wrists), trunk (lumbosacral area), shins, glans penis (Figs 5.23A and B). Nape of neck, wrist, ankle, genitalia, and perianal area (Figs 5.24A and B). Herald patch-trunk. Daughter patches-Christmas tree pattern over the trunk (Figs 5.25A and B). Extensor aspects of limbs, scalp, lumbosacral area (Figs 5.26A and B). Infants-Face, intertriginous area of fingers, palms and soles, extensor aspect of limbs, around umbilicus, genitalia and gluteal area (Figs 5.27A and B). Children and adults-finger web spaces, wrist, elbows, axillary fold, around areola and umbilicus, genitalia, and gluteal area (Figs 5.28A and B). Infants-Cradle cap over scalp (Figs 5.29A and B). Adolescence and adults- scalp, eyebrows, nasolabial folds, presternal and interscapular area, axilla and groin (Figs 5.30A and B). Upper trunk (Figs 5.31A and B).

Figs 5.20A and B: Distribution of skin lesions in atopic dermatitis in infants

Figs 5.21A and B: Distribution of skin lesions in atopic dermatitis in children and adults

Principles of Diagnosis in Dermatology

Figs 5.22A and B: Distribution of skin lesions in dermatitis herpetiformis

Figs 5.23A and B: Distribution of skin lesions in lichen planus

Figs 5.24A and B: Distribution of skin lesions in neurodermatitis (lichen simplex chronicus)

Figs 5.25A and B: Distribution of skin lesions in pityriasis rosea

Figs 5.26A and B: Distribution of skin lesions in psoriasis vulgaris

Figs 5.27A and B: Distribution of skin lesions in infants in scabies

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Figs 5.28A and B: Distribution of skin lesions in children and adults in scabies

Figs 5.29A and B: Distribution of skin lesions in seborrhoeic dermatitis in infants

Figs 5.30A and B: Distribution of skin lesions in seborrhoeic dermatitis in adolescence and adults

Figs 5.31A and B: Distribution of skin lesions in tinea versicolor

Certain phenomenon and signs are there to be seen and observed; others need to be elicited by tools.

of dermatological disorders such as psoriasis (Fig. 5.32), lichen planus, vitiligo, eczema, dermatitis herpetiformis, bullous pemphigoid, warts (Figs. 33 and 34), molluscum contagiosum (Fig. 5.35), etc. • Reverse Koebner phenomenon: Area of psoriasis clears of following injury. • Remote reverse Koebner phenomenon is the spontaneous repigmentation of vitiligo patches distant from the autologous skin graft sites.

• The Koebner phenomenon: The Koebner phenomenon is the development of morphologically identical lesion/s in the traumatized uninvolved skin of patients who have cutaneous diseases. It is also known as isomorphic phenomenon, a self-explanatory term. This phenomenon is observed in a number

Principles of Diagnosis in Dermatology

Fig. 5.32: Koebner phenomenon in psoriasis vulgaris over the trunk

Fig. 5.33:Koebner phenomenon in plane warts over the wrist

Fig. 5.34: Koebner phenomenon in verruca vulgaris

Fig. 5.35: Koebner phenomenon in molluscum contagiosum

• Dermographism: It can be elicited with the help of blunt instrument like key. Firm stroking of skin may result in exaggerated triple response of Lewis, which persists for more than 5 minutes. Stroking causes histamine to be released, leading to localised redness and edema (Wheal). Dermographism can occur in urticaria.

• Darier’s sign: When the above phenomenon is limited to skin overlying a lesion (macule or papule), it is called as Darier’s sign and is diagnostic of urticaria pigmentosa (Mast cell disease). • Pseudo-Darier’s sign: Here stroking of skin produces transient induration with pilo-

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Essentials in Dermatology

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erection, seen in congenital smooth muscle hamartoma White dermographism: Stroking the skin of atopic patients produces a characteristic white line in the involved area. Grattage test: It is done on a scaly lesion to look for types of scales. Scraping of the lesion is done with a glass slide. Fine powdery scales of tinea versicolor can be made out if you examine the glass slide against light after scraping the lesion. Candle sign and last cuticle sign: In psoriasis, if the silvery-white scales are scraped off, they detach from the lesions as small flakes, similar to wax scraped from candle. With continued scraping, one can remove a coherent moist sheet from the lesion corresponding to the lowest layers of epidermis. Auspitz’s sign: This sign if present is diagnostic of psoriasis. It has three components. 1. On scraping with glass slide, initially silvery white micaceous scales come out. 2. Removal of the scales is followed by a thin membranous structure. 3. On its removal by glass slide, minute pinpoint bleeding spots are seen. Diascopy (Vitropression): It is based on the principle that vascular lesions will blanch in response to pressure with a glass slide whereas purpuric lesions, in which blood and blood pigments have leaked from the cutaneous vessels, will not blanch. Diascopy is most useful in detection of nonblanchableraised purpura, the clinical hallmark of cutaneous vasculitis. It is useful in differentiating nevus anemicus from nevus depigmentosus. Nevus anemicus (a localised area of vasoconstriction) on diascopy of adjacent skin reveals an identical color to depigmented area. By contrast diascopy of skin adjacent to nevus depigmentosus or vitiligo, the affected area still remains paler.

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Apple jelly nodules in lupus vulgaris active edge of the lesion, appear as translucent brownish color granulomatous nodules, a distinctive feature of the disease. Ollendorf’s sign: If touching of the papule of secondary syphilis with the head of pin is exquisitely tender, then Ollendorf’s sign is said to be present. Nikolsky’s sign: A frictional force is applied with a finger or thumb over the apparently normal skin, usually overlying a bone like the clavicle or perilesional skin in a patient with vesiculo-bullous lesions. If epidermis or surface of the skin breaks down or peels off leaving raw moist erosion, it is called positive Nikolsky’s sign. Various disorders, in which Nikolsky’s sign is positive, are pemphigus, staphylococcal scalded skin syndrome, toxic epidermal necrolysis, etc. This test is based on the fact that in certain diseases, even the normal looking skin has a weak cohesion between its different layers. Bulla spread sign: It can be demonstrated by marking the boundary of the bulla and then applying pressure with a finger on the edge of the bulla. In pemphigus, bulla spreads beyond the marked line showing that active process of acantholysis has weakened the cohesion between keratinocytes. Button holing sign: In neurofibromatosis, if fingertip is pressed over neurofibroma, the finger gapes in due to defect in the dermis. Dimple sign: It distinguishes dermatofibroma from malignant melanoma. Applying lateral pressure with thumb and index finger –results in formation of a dimple in dermatofibroma, whereas melanoma protrudes above its original plane. Hess test or Capillary fragility test: A blood pressure cuff is applied to upper arm between systolic and diastolic pressure for 5 minutes. The number of petechiae in predetermined area of 5 cm circle is counted.

Principles of Diagnosis in Dermatology If number is more than 5, it is abnormal capillary fragility. • Pathergy test: Inject 0.1 ml of physiologic saline intradermally with fine needle over the forearm. Read after 24-48 hours. Pustules or papules suggest the diagnosis of Behcet’s disease. Histology shows neutrophilic infiltrate or vasculitis. • Testing sensation and palpation of peripheral nerves may be required to fulfil one of the cardinal features of leprosy and thus help in its diagnosis.

LABORATORY AND SPECIAL TESTS They may be needed to confirm the diagnosis: 1. Wood’s light examination: It is useful in detecting fungal infections of the scalp (bluish-green fluorescence in tinea capitis caused by Microsporum species—Microsporum canis and Microsporum audouinii), tinea versicolor (yellow fluorescence), erythrasma (coral red fluorescence), porphyrins in patients with porphyria cutanea tarda (Urine will produce bright red fluorescence), trichomycosis axillaris (orange fluorescence), Pseudomonas infection (green fluorescence), etc. In scabies, fluorescein solution fills burrows. In pigmentary disorders, vitiligo, piebaldism, and ash leaf macules of tuberous sclerosis, the lesions become prominent. 2. KOH preparation: Indicated when infection with fungi or yeast is suspected, e.g. dermatophytosis, tinea versicolor, candidiasis, etc. 3. Tzanck test: It is used in the diagnosis of various skin disorders characterised by vesicles, pustules, bullae and erosions and in particular in viral infections like herpes simplex, herpes zoster and varicella infections.

4. Gram’s stained pus smear: Indicated for pyogenic infections, vaginal and urethral discharge. 5. Tissue smear: It is used for diagnosis of donovanosis (granuloma inguinale). 6. Dark field (ground illumination) test: Primary and secondary syphilis can be easily diagnosed by demonstrating treponemes. 7. Wet preparation: It is utilized for diagnosis of trichomonal infestation of the genital tract. 8. Slit skin smear: This test is performed on leprosy patients to demonstrate acid-fast bacilli in skin smears. 9. Lepromin test: It is useful for classification of leprosy and is strongly positive in tuberculoid leprosy and mildly positive in borderline tuberculoid leprosy. It is negative in borderline borderline, borderline lepromatous and lepromatous leprosy. 10. Dermatoscopy (Epiluminescence microscopy, dermoscopy): Method of observing superficial layers of skin using 10-100 X magnification with oil immersion. Both hand held and computer assisted instruments are available. It is used for differential diagnosis of pigmented skin lesions, melanoma, for detailed examination of nail fold capillaries, Wickham’s striae, scabies burrows (hang glider sign), surface of verrucae and the scalp surface (cadaver hairs and exclamation point hairs suggest alopecia areata, loss of follicular openings indicates scarring alopecia and follicular hyperkeratosis point towards lichen planus). 11. Biopsy: Most frequently skin biopsy is taken to confirm a clinical diagnosis or to aid in the establishment of a diagnosis where clinical diagnosis is not apparent.

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Essentials in Dermatology 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.

VDRL HIV antibody detection test Culture and sensitivity test Patch testing Prick testing Intradermal testing LE cell phenomenon Mouse foot pad inoculation Immunofluorescence Hair examination and counts Trichogram- method for analyzing hair bulbs to identify in what stage hairs are being lost and thus to distinguish between different types of hair loss. 23. Electron microscopy

Five Thoughts for the Students in the Field Of Dermatology 1. Diagnosis is the art of recognition, not the science of cognition 2. The best diagnosticians are the ones with the best visual memories 3. The best history is taken by one who already knows the diagnosis 4. If puzzled, limit yourself to three working diagnoses. 5. A good colour atlas (a memory of 75 diseases allows you to immediately recognize 95% of all the skin lesions you will ever see) and a good dermatopathologist are your best friends.

Bacterial Infections

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Bacterial Infections

Normal human skin is colonized soon after birth by a large number of bacteria that live as commensal on the epidermis and epidermal appendages. Coagulase negative staphylococci (S. epidermidis) are inoculated during vaginal passage; coryneform bacteria take up residence on neonatal skin shortly after birth; and within several weeks after birth, the flora of neonatal skin is similar to that of adults. Staphylococcus aureus is persistent member of the microbial flora in 10 to 20% of the population. As many as 84% of healthy individuals have occasional carriage of S. aureus in their anterior nares.

PYODERMAS Pyoderma is a common purulent infection of the skin caused by staphylococcal or streptococcal organisms. They can be classified as primary pyodermas and secondary pyodermas (Table 6.1).

Primary pyodermas are further divided into non-follicular and follicular for clinical application (Table 6.2) and on the basis of organism involved (Table 6.3).

Staphylococcal Pyodermas

Impetigo Non-bullous impetigo (Impetigo contagiosa of Tilbury Fox): • It is caused by S. aureus or group A Streptococcus or both • Occurs in children of all ages, common in preschool and young school children • Commonly over the face (especially around nares) or extremities after trauma • The initial lesion is a transient vesicle or pustule that quickly evolves into a honey coloured crusted plaque (Fig. 6.1) • Surrounding erythema may be present

Table 6.1: Distinctive features of pyodermas

Primary pyodermas 1. Invasion of normal skin by bacteria 2. Single species of bacteria involved 3. Appearance of lesions is characteristic e.g., impetigo, erysipelas, furuncle 4. Treatment is clear cut – Drugs aimed at the microorganism

Secondary pyodermas 1. Develop in areas of already damaged/compromised skin 2. Mixture of organisms involved 3. Not characteristic 4. Role of antibacterial treatment less defined. Here, the aim is to treat the underlying process

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Essentials in Dermatology Table 6.2: Non-follicular and follicular pyodermas A. Non follicular pyodermas include 1. Impetigo 2. Ecthyma 3. Cellulitis 4. Erysipelas 5. SSSS B. Follicular pyodermas include 1. Folliculitis 2. Furuncle 3. Carbuncle

• Regional lymphadenopathy in up to 90% of patients with prolonged untreated infection • In severe cases, there may be fever, adenitis and constitutional symptoms • Differential diagnosis: 1.Tinea corporis – has dry, scaly, advancing edge with central clearing. 2. Ecthyma- characterized by crusted ulcers (not erosions).

Bullous Impetigo Table 6.3: Cutaneous diseases caused by staphylococci and streptococci 1. Cutaneous diseases caused by staphylococcus include: A. Direct infection of skin: Impetigo, ecthyma, folliculitis, furunculosis, carbuncle, sycosis. B. Due to effect of bacterial toxin:SSSS, TSS. 2. Cutaneous diseases caused by streptococcus: A. Direct infection of skin: Impetigo, ecthyma, erysipelas, cellulitis, vulvovaginitis, perianal infection, blistering dactylitis, necrotizing fasciitis. B. Due to effect of bacterial toxin: Scarlet fever, toxic shock like syndrome

Fig. 6.1: Impetigo contagiosa–honey colored crusted lesions over the face of a child

• Earlier bullous impetigo in neonates was popularly known as pemphigus neonatorum. • S. aureus (phage group II) is the causative agent. • Occurs commonly in the newborn and in older infants. • Bullae (flaccid) rapidly evolve from vesicles on areas of grossly normal skin (Fig. 6.2) due to local production of exfoliative toxin A and B. • Differential diagnosis: Pemphigus vulgaris-Generally occurs in young adults. Erosions show no tendency to heal, Nikolsky’s sign and bulla spread sign are positive. More importantly, mucosal erosions are more commonly associated feature.

Fig. 6.2: Bullous impetigo–large pus filled blisters over the trunk of a child

Bacterial Infections Complications of Impetigo • Post-streptococcal acute glomerulonephritis– S. pyogenes type M-49 • Scarlet fever • Urticaria • Erythema multiforme Rheumatic fever in not a complication of streptococcal skin infection (but of streptococcal sore throat).

Ecthyma • Consequence of neglected impetigo • S. aureus and/ or group A Streptococcus are causative agents • Most commonly occurs on the lower extremities of children or neglected elderly patients • Poor hygiene and neglect are key elements in pathogenesis. • Dirty grayish-yellow crust surmounts a “punched out” ulcer (Fig. 6.3).

Fig. 6.3: Ecthyma–crusted lesion over the leg with ulcerated lesions

Folliculitis Pyoderma affecting the hair follicles, classified according to depth of invasion. Superficial folliculitis • Also known as follicular or Bockhart’s impetigo • A small fragile dome shaped pustule occurs at the infundibulum of a hair follicle, often on scalps of children and in the beard area, axilla, extremities and buttocks of adults. • Differential diagnois: Miliaria pustulosa – non follicular pustules are wide spread, which occur in hot and humid conditions Deep folliculitis Sycosis barbae is a deep folliculitis with perifollicular inflammation occurring in the bearded areas of the face (Fig. 6.4) and upper lip. Differential diagnosis 1. Pseudofolliculitis– Papules/pustules are irregularly scattered at the site of ingrowing beard hairs. Neck and angle of jaw (vs. sycosis barbae– upper lip and below angles of jaw) are preferentially involved. 2. Tinea barbae– Site involved is usually submaxillary region or the chin. Hairs are

Fig. 6.4: Sycosis barbae– grouped follicular based crusted lesions in the beard area of the face

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Essentials in Dermatology broken or loosened (easy and painless pluckablity) in the affected area. Loss of hair is the norm. Suppurative or granulomatous nodules rather than pustules characterize this condition. Spores and hyphae can be demonstrated in the hair by KOH examination. 3. Herpetic sycosis is usually limited for a few days and invariably shows vesicles even in persistent lesions 4. Acne vulgaris is polymorphous condition mainly of glabrous skin of the face where comedones are the hallmark of that condition Lupoid sycosis is deep, chronic form of sycosis barbae associated with scarring usually occurring as circinate lesion. Pustules and papules surround a central scar (Fig. 6.5). Differential diagnosis: Lupus vulgaris is characterized by areas of scarring on one side and progression on the other side. There is absence of pustules in the lesions but it demonstrates apple jelly nodules on diascopy.

Furuncles and Carbuncles • A furuncle or boil is a deep-seated inflammatory nodule that develops about a hair follicle, often evolving into an abscess (Fig. 6.6). They arise in hair bearing areas,

Fig. 6.5: Lupoid sycosis–scarring alopecia in the beard area showing active pustular lesions at the periphery

particularly in regions subject to friction, occlusion, and perspiration. Differential diagnosis: FolliculitisInflammatory change is confined within the follicle without any surrounding inflammation – hence presents as a pustule whereas furuncle presents as a nodule. There is less pain and it heals without scar formation. Cystic acne- Associated with other lesions of acne – comedones, papules and pustules and acne scars and it is confined to face and trunk. • A carbuncle is a cluster of furuncles, more extensive, deeper, communicating, in filtrated lesion that develops when suppuration occurs in elastic skin. It usually involves the nape of the neck, back or thighs and usually occurs in the setting of underlying diabetes mellitus, alcoholism, malnutrition, blood dyscrasias, iatrogenic or other immunosuppression including HIV infection. Fever, malaise, prostration accompany. Differential diagnosis: Anthrax – characterized by painless, hemorrhagic crusted (blackish eschar) lesion with surrounding gelatinous edema out of proportion to the extent of the lesion.

Fig. 6.6: Furuncle–a red tender suppurated nodule in a case of erythroderma

Bacterial Infections compromise. Typically, the patient has fever and is irritable. The changes usually begin periorificially or in body folds (Figs 6.7 and 6.8). Then they spread rapidly. Nikolsky’s sign is positive even on apparently normal skin. One should culture the perineum, eyes, ears, nose and throat, looking for S. aureus as the focus of infection is located at a distant site. The bacteria can not be cultured from the skin. For differential diagnosis Table 6.4.

Staphylococcal paronychia: Clinically, skin and soft tissue of proximal and lateral nail fold are red, hot and tender, and if not treated, can evolve to abscess formation. In contrast, chronic or recurrent paronychia caused by Candida albicans is an infection of the space underneath the nail folds.

Toxin Mediated Syndromes Staphylococcal scalded skin syndrome (SSSS) (Ritter’s disease) • This is the most severe form of skin disease due to the exfoliative exotoxins (A and B) produced by S. aureus of group II, phage type 71 or 55 and is characterized by generalized bulla formation and exfoliation. Most commonly involves neonates and young children, but also in adults with renal

Toxic Shock Syndrome • TSS is a multiorgan systemic illness due to exotoxin (TSS-Toxin 1) producing strains of S. aureus. • Case definition 1. Temperature of 38.9oC or higher 2. Erythematous eruption

Fig. 6.7

Fig. 6.8

Figs 6.7 and 6.8: SSSS–typical periorificial and body fold involvement with peeling skin

Table 6.4: Differential diagnosis of SSSS from toxic epidermal necrolysis (TEN)

Staphylococcal scalded skin syndrome (SSSS) 1. 2. 3. 4. 5. 6.

Age – less than 5 years Skin shows marked tenderness Distribution – face, neck , axilla, groin Mucoca – not involved Prognosis – good Histology – subgranular split due to acantholysis

TEN 1. 2. 3. 4. 5. 6.

More than 40 years Mild to moderate tenderness No clear distribution Involved Poor Necrosis of epidermis

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Essentials in Dermatology 3. Desquamation of palms and soles 1 to 2 weeks after onset 4. Hypotension 5. Involvement of 3 or more other organ systems • About 85 to 90 percent of cases of TSS have occurred in women at the time of menstruation; almost all had been tampon users (particularly of super absorbent types). • Differential diagnosis: 1. SSSS– It has the presence of bullae, Nikolsky’s sign is positive with skin tenderness, but systemic organs are not involved and patient appears wellpreserved. 2. Scarlet fever– not usually associated with hypotension and shock. 3. Kawasaki’s syndrome– prolonged fever, cardiac involvement, generalized lymphadenopathy and absence of peripheral shock.

•

• • • • • •

of subcutaneous tissue whereas erysipelas is a bacterial infection of the dermis and upper subcutaneous tissue. Erythema, warmth, swelling and tenderness are constant features (Fig. 6.9). In erysipelas, the edge of the lesion is well defined and raised, but in cellulitis it is diffuse. In erysipelas, blistering is common. Except in mild cases, there are constitutional symptoms. The leg is the commonest site; the next most frequent site for classical streptococcal erysipelas is face. Milian’s sign – cellulitis of the face does not involve pinna, unlike erysipelas (as there is no subcutaneous tissue there). Without effective treatment, complications are common-fasciitis, myositis, subcutaneous abscesses, septicaemia, and nephritis. For presumed streptococcal infection, penicillin is the treatment of choice.

Streptococcal Pyodermas The major pathogen belongs to group A and is referred to as Streptococcus pyogenes. Streptococci colonise damaged skin, although less frequently than staphylococci. Major complications following streptococcal infection are rheumatic fever (following Streptococcal pyogenes pharyngitis), acute glomerulonephritis (both throat and skin infection), erythema nodosum and guttate psoriasis, and scleredema of Buschke (following throat infection). Impetigo and Ecthyma already discussed. Crowding, poor hygiene, and neglected minor skin trauma contribute to the spread of streptococcal impetigo in families.

Cellulitis and Erysipelas • Predominantly streptococcal disease, Staphylococcus aureus is occasionally implicated. • Cellulitis is an acute, subacute or chronic infection of loose connective tissue, mainly

Fig. 6.9: Cellulitis–lower leg showing shiny erythema and edema

Bacterial Infections

Blistering Dactylitis • This is nearly always a group A streptococcal infection in children or teenagers. • A large blister containing thin seropurulent fluid forms on the distal phalanx, usually of a finger, typically on a phalangeal pad.

Perianal Streptococcal Infection • It occurs in children aged 1-10 years and is characterized by intense perianal erythema, perianal soreness, pain on defecation, faecal retention and blood-streaked stools.

Streptococcal Vulvovaginitis • Streptococcus pyogenes accounts for 10% of cases of vulvovaginitis in prepubertal girls.

Toxin Mediated Streptococcal Disease • Scarlet fever and streptococcal toxic shock like syndrome are due to toxins. • Scarlet fever is a diffuse erythematous eruption resulting from the production and subsequent circulation of pyrogenic exotoxins A, B, C (erythrogenic toxin) produced by group A streptococci usually located in pharynx. Incubation period – 2 to 5 days – starts with an acute tonsillitis. Rash appear on the 2nd day as finely punctuate erythema “Sunburn with goose-pimples”. Other features include Pastia’s lines (transverse streaks in the skin folds due to capillary fragility), pallor around mouth, red strawberry tongue, and high fever. Myocarditis may complicate this condition. • Group A streptococci cause an acute multisystemic syndrome coined toxic-shock –like syndrome (TSLS) resembling that caused by S. aureus.

• It is not only caused by group A streptococci but also due to other bacterial species (mixture of anaerobes/facultative organisms).

Diagnosis 1. Gram’s stained smear from the purulent material may demonstrate streptococci or staphylococci or both. 2. Culture and sensitivity: Swabs taken from infected sites may be sent for culture and sensitivity, so that appropriate antibiotic may be instituted to treat the condition. 3. Tzanck smear in SSSS shows acantholytic cells. 4. Histopathology: Histopathological examination is hardly required for the diagnosis. Treatment 1. General measures such as improved hygiene, loose light weight porous clothing, regular bathing, use of antiseptics in bath, antibacterial soaps, etc.

Necrotizing Fasciitis (Streptococcal gangrene) • It represents cellulitis that has progressed to gangrene of subcutaneous tissue followed by necrosis of overlying skin (Fig. 6.10).

Fig. 6.10: Necrotizing fascitis—cellulitis progressing to gangrene over the leg

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Essentials in Dermatology 2. Wet compresses: Condy’s compresses for crusted lesions of pyoderma. 3. Incision and drainage is indicated when furuncle has become localized and shows definite fluctuation. 4. Topical antibacterial agents such as gentian violet, neomycin, fusidic acid or mupirocin. 5. Systemic antibacterial agents: Systemic antibiotic therapy is indicated– i. For extensive lesions of pyoderma ii. For erysipelas, cellulitis, carbuncle, furunculosis, SSSS, etc. Penicillin is preferred for streptococcal infection whereas penicillinase resistant penicillin such as cloxacillin and cephalosporins are required for staphylococcal infections. Oral antibiotics (e.g., rifampicin 600 mg orally daily for 10 days) have been effective in eradicating S. aureus from most nasal carriers for periods of up to 12 weeks in cases having recurrent furunculosis. Intranasl application of 2% mupirocin ointment for 5 days can eliminate S. aureus nasal carriage in 70% of healthy individuals for up to 3 months.

NON-PYODERMAS Erythrasma • Causative agent-Corynebacterium minutissimum, diphtheroids bacillus, gram positive, non spore forming rod shaped organism. • Bacterial infection of the intertriginous areas like axilla, groin, gluteal cleft, inframammary folds, umbilicus and toe web spaces. • Usually manifest with asymptomatic red brown macules with sharp border (Fig. 6.11). • The best way to make the diagnosis is Wood’s light examination for coral red fluorescence. • Differential diagnosis: Hyperpigmented tinea versicolor (asymptomatic in nature) may appear like erythrasma. It predominantly affects upper trunk, individual lesions are small, but not erythematous and satellite lesions are more commonly seen than

Fig. 6.11: Erythrasma–asymptomatic brownish macular lesion with fine scaling in the axilla

erythrasma. KOH examination and culture from the lesions may clinch the diagnosis. Tinea cruris is characterized by pruritic well defined annular plaques with peripheral rim of papulopustules, and satellite lesions. • C. minutissimum can be cultured under aerobic condition • A short course of systemic erythromycin is the easiest method of treatment. Topical imidazole creams are also effective.

Trichomycosis Axillaris • Causative agent- Corynebacterium tenuis. • Collections of this bacteria forms concretions on hairs, usually in the axilla. • The axillary hairs are surrounded by whiteyellow (Fig. 6.12), red or black, difficult to remove concretions that extend for several centimetres. • Diagnosis is established by examining hair under microscope (Fig. 6.13), if necessary to culture the organism.

Bacterial Infections

Fig. 6.14: Pitted keratolysis–soles demonstrating multiple pits

Fig. 6.12: Trichomycosis axillaris–yellow discoloration of axillary hairs due to concretions

Fig. 6.13: Trichomycosis axillaris–same patient's axillary hair under light microscope showing concretions over the hair shaft

• Differential diagnosis: Phthiriasis pubis can be differentiated by its associated pruritis and crawling sensation. Piedra can be differentiated by its gritty hard feeling and by doing a KOH examination. • The easiest treatment is to shave the area and treat the regrowing hairs with any topical disinfectant.

Pitted Keratolysis • Causative agent- Corynebacterium species, Streptomyces species, Dermatophilus congolensis and Micrococcus sedentarius. • Multiple pitted defects, 2-5 mm in size occur in thick horny layer of soles (Fig. 6.14). • The key factor is maceration, usually arising from hyperhidrosis, prolonged wearing of shoes and improper hygiene. • Differential diagnosis: The lesions are easily recognizable, but simple hyperhidrosis, erythrasma and tinea pedis have to be considered. • Topical erythromycin solution or benzoyl peroxide gel can be applied once or twice daily. Remove aggravating factors, if possible. Botryomycosis • Botryomycosis is a chronic suppurative, granulomatous disorder of bacterial origin. True non- filamentous aerobic and anaerobic bacteria such as Staphylococcus aureus, Pseudomonas species, Proteus vulgaris, Escherichia coli or Micrococcus cause it. • Botryomycosis needs to be differentiated from two other granulomatous diseases that

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•

Fig. 6.15: Botryomycosis–swelling of the foot with multiple nodules over it

form granules - mycetoma and actinomycosis, since clinically it has similar features (Fig. 6.15). • Effective treatment of botryomycosis depends on various factors such as the causative agent, location of the lesion and immune status of the host. Various drugs, mostly as single agents given for several weeks, have been successfully used in botryomycosis including trimethoprimsulfamethoxazole, minocycline, erythromycin and cefazolin. In addition to antibiotics, surgical excision and drainage of lesions may be useful in certain patients.

Actinomycosis • Actinomycosis is a chronic suppurative infection caused by anaerobic Actinomyces species. Actinomycetes are bacteria producing filamentous and branching hyphae. • Pathogenic organisms of these genera, namely Actinomyces israelii exists as a commensal in the oral cavity, tonsillar crypts and genital mucosa. • This organism gains entry when there is a disruption of mucosal barrier in the form of trauma or surgery. The resultant disease, actinomycosis is characterized by an early

•

• •

• •

inflammatory phase which resembles cellulitis and a more typical chronic phase, which presents as single or multiple indurated swellings (usually fibrosis). These swellings become soft and fluctuant and later suppurate, sometimes forming sinus tracts discharging yellow colour granules. These so called “sulphur granules” are lobulated masses of intertwining filaments. Human infections are categorized based on anatomical sites, namely cervicofacial (lumpy jaw), thoracic, abdominal, pelvic and primary cutaneous. Cervicofacial actinomycosis is the most common clinical presentation. It commonly follows dental extraction and presents as painful, indurated soft tissue swelling located at the angle of the jaw. Thoracic infection occurs due to aspiration and it involves lungs and pleura. Actinomycosis of gastrointestinal tract most commonly develops in ileocecal region and presents as appendicitis or slow growing mass. Pelvic actinomycosis occurs in women and is usually associated with the use of intrauterine device. Primary cutaneous actinomycosis is a rare type and probably occurs due to direct implantation of the organism. It usually occurs on the exposed skin (Fig. 6.16).

Fig. 6.16: Actinomycosis–scalp showing ulcerated indurated nodules with sulphur granules

Bacterial Infections

Cutaneous Anthrax • Causative agent- Bacillus anthracis, gram positive bacillus, • The most common form of infection with Bacillus anthracis is an acute cutaneous lesion called “malignant pustule.” • Anthrax is primarily a disease of domestic and wild animals, but humans become accidentally involved through exposure to animals and their products. • Human anthrax occurs in three clinical forms: 1) cutaneous anthrax due to direct contact

with contaminated meat, carcasses, hides, hair, wool or bone, 2) inhalational anthrax (Woolsorter’s disease) due to inhalation of spores and 3) gastrointestinal anthrax due to ingestion of contaminated meat or milk. Anthrax meningitis occurs secondary to skin lesions, but it can complicate the other two forms also. • Cutaneous anthrax usually begins as a painless, pruritic papule within 3 to 10 days of inoculation. It rapidly progresses into a serous or serosanguineous vesicles, which ulcerate with a central black eschar, surrounded by a ring of vesicles within 36 hours (Figs 6.17 and 6.18). Perilesional oedema can be extensive. Toxic features occur in 50% of cases only and healing occurs in 1 to 3 weeks with variable scarring. • The following clinical features are strongly suggestive of cutaneous anthrax 1. The presence of edema out of proportion to the size of the lesion. 2. Lack of pain during the initial phases of the infection. 3. The rarity of polymorphonuclear leucocytes from vesicular fluid on gram’s stain and distinctive box car arrangement of bacillus anthracis (Fig. 6.19).

Fig. 6.17

Fig. 6.18

• A definite diagnosis of actinomycosis cannot made be on clinical grounds alone. Demonstration of sulphur granules, grams stain and culture from the appropriately obtained specimen is needed to confirm the diagnosis. Histopathology reveals granular colonies from which delicate mycelial filaments radiate. These colonies are surrounded by a chronic inflammatory infiltrate. • Actinomycosis may resemble various chronic inflammatory diseases such as tuberculosis, syphilis, etc. • Dramatic response to penicillin therapy occurs.

Figs 6.17 and 6.18: Cutaneous anthrax (Malignant pustule)–typical painless lesion with central blackish eschar surrounded by wreath of erythema, edema and vesiculation

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Essentials in Dermatology Ciprofloxacin, erythromycin, tetracycline and chloramphenicol are alternative drugs for penicillin sensitive patients.

Fig. 6.19: Anthrax–"Box car" arrangement of bacillus anthracis in gram's stained smear

• Differential diagnosis: Carbuncle Tenderness is prominent and there is presence of multiple furuncles in a group. Cow pox and sporotrichosis are other differential diagnoses. The history, rapid course, clinical appearance and lack of lymphangitis should suggest the diagnosis of anthrax which should be confirmed by bacteriological examination. • Since 20% of untreated cases of cutaneous anthrax develop bacteraemia, which leads to rapid death, cutaneous anthrax should be treated energetically with penicillin.

Bacillary Angiomatosis • Causative agent: Bartonella henselae (organism also causes Cat Scratch disease); rarely Bartonella quintana. • Infection is most common in HIV/AIDS patients, causes endothelial proliferation and produces vascular tumors. • Clinically, lesions are rapidly growing pyogenic granuloma like papules and nodules, which often ulcerate. • Purple, papular and nodular vascular lesions may resemble Kaposi’s sarcoma. • Diagnosis is based on demonstration of organism in the skin biopsy tissue section by Warthin Starry staining. Blood cultures are positive in half of the cases. • Differential diagnosis: Pyogenic granuloma and Kaposi’ sarcoma are close differential diagnosis, differentiation can be made by histopathological examination and demonstration of the organism by Warthin starry staining. • The mainstay of treatment is erythromycin. Alternatively, doxycycline or ciprofloxacin can be used.

Viral Infections

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Viral Infections

Many viral infections have cutaneous manifestations. These infections may sometimes be limited to the skin as in warts or molluscum contagiosum. In systemic viral infections, the frequency of skin lesions may range from almost always, as in varicella, to infrequently, as in cytomegalovirus. Viral infections of skin are characterized by a definite morphology and distribution. Most of the infections can be clinically diagnosed fairly and accurately without the need of sophisticated laboratory diagnostic aids. Five groups of viruses can affect the skin or adjoining mucous membrane surfaces. All except two (picorna virus group and retroviruses group) belong to DNA viruses. Viruses can be seen with the light microscope only when aggregated into inclusion bodies. Inclusion bodies are roughly spherical. Their average size is about 7 µm, the size of an erythrocyte. They are seen in three groups of viruses and are of two types. 1. Intranuclear inclusion bodies are seen in the herpes virus group and papilloma virus group. 2. Intracytoplasmic inclusion bodies are seen in the poxvirus group. In India, molluscum contagiosum is the predominant viral skin infection followed by

warts, herpes simplex, herpes zoster and chicken pox.

MOLLUSCUM CONTAGIOSUM • Molluscum contagiosum is caused by up to four closely related types of poxviruses, MCV-1 to - 4 and their variants. • The incubation period for the molluscum contagiosum (MC) has been reported to be between 14 and 50 days. • Skin to skin transmission is presumed to be the method of spread, including autoinoculation (the Koebner phenomenon), as well as contact with fomites. • It mainly affects children, sexually active adults and persons with impaired cellular immunity including HIV infection • In small children, virtually all infections are caused by MCV-1 whereas in patients infected with HIV, however, MCV-2 causes the majority of infections (60%), suggesting that HIV infection associated molluscum does not represent recrudescence of childhood molluscum. In all forms of infection, the lesions are relatively similar. • Individual lesions are smooth surfaced, firm, dome shaped pearly papules averaging 3 to 5 mm in diameter. Some

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Fig. 7.1: Molluscum contagiosum—typical umbilicated papule

Fig. 7.2: Molluscum contagiosum—lesions occurring over the face in a child

Fig. 7.3: Molluscum contagiosum—lesions occurring over genitalia in a child

“giant” lesions may be up to 1.5 cm in diameter. • A central umbilication is characteristic (Fig. 7.1) • Children more typically develop lesions on the face (Fig. 7.2), trunk and extremities, although perineal, scrotal (Fig. 7.3), perianal (Fig. 7.4), and groin lesions may be present as part of a wider distribution. • Clinically, molluscum in HIV positive persons appears to be transmitted both by sexual and nonsexual routes. The lesions are

Fig. 7.4: Molluscum contagiosum—lesions over the gluteal area and thigh in a child

more common on the face and neck (Figs 7.5 and 7.6).

Diagnosis • It is made clinically when necessary, histological examination is diagnostic.

Viral Infections

Fig. 7.5: Molluscum contagiosum—lesions around eye in a HIV patient

Fig. 7.6: Giant molluscum contagiosum just below the eye in an adult HIV patient

• Microscopic examination of a lesion crushed on a slide and left stained or unstained with Wright’s, Giemsa, Gram’s, or Papanicolaou stains demonstrates the inclusion bodies (Henderson Paterson bodies).

• Oral cimetidine or intravenous cidofovir can be used in widespread lesions.

Differential Diagnosis • Solitary MC may resemble pyogenic granuloma, keratoacanthoma or epithelioma. • Cutaneous cryptococcos is histoplasmosis, Penicillium marneffei infection, and basal cell carcinoma have been mistaken for molluscum in patients with AIDS.

• Human papillomavirus (HPV) has been associated with a broad spectrum of disease that ranges from asymptomatic latent infection to warts to squamous cell carcinoma. • This virus infects mucosal and cutaneous sites of immunocompetent as well as immunosuppressed patients. • It represents the most common mucocutaneous viral infection, and 3 to 5% of all patients have clinically evident warts. • Warts, or verrucae, are benign proliferations of the skin and mucosa that result from infection with papillomavirus. • These viruses do not produce acute signs or symptoms but induce slow-growing lesions that can remain subclinical for long periods of time. • These warts assume many clinical forms – common warts (verrucae vulgaris), filiform warts (digitate warts), flat warts (verrucae plana), plantar warts, genital warts (condylomata acuminata), oral and laryngeal

Treatment • In children, they may be left alone • Curettage– Individual lesions can be treated with curettage • Trichloroacetic acid (30-100%) application • 10% KOH application • Podophyllin – 10% to 25% • Silver nitrate • 5-FU topically • Cryosurgery • Electrodesiccation • Topical cantharidin, tretinoin (0.05% - 0.1%), cidofovir (1-3%), and imiquimod (5%) are other options

HUMAN PAPILLOMAVIRUS INFECTION (WARTS)

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papillomas and epidermodysplasia verruciformis. HPV types 1,2,3,4,7 cause first four forms of warts commonly. Genital warts are usually due to HPV types 6, 11, 16 and 18. Warts occur at any age, but are unusual in infancy and early childhood, the incidence of warts increases during the school years. Incubation period has been estimated to range between a few weeks to more than 1 year. Warts are spread by direct or indirect contact. Impairment of epithelial barrier function by moisture or trauma is predisposing factor.

• Paring shows multiple bleeding points or black dots representing thrombosed capillaries in warts. • Corns have a hard, painful translucent central core. • Lateral pressure on a wart causes pain, but corn is painful on vertical pressure. Plane warts: They are due mainly to HPV 3 and 10, and are smooth, flat or slightly elevated, skin colored or pigmented. The face (Fig. 7.8) and the backs of hand and shin are the sites of predilection. In differential diagnosis, lichen

Common warts: They are due mainly to HPV-2 and are characterized by symptomless, firm papules with a rough, horny surface, range in size from less than 1 mm to over 1 cm in diameter, and by confluence can form large masses. They are most commonly situated on the backs of hands and fingers (Fig. 7.7). They need to be differentiated from calluses. Warts do not have dermatoglyphics as opposed to calluses in which these lines are accentuated. Plantar warts: A plantar wart at first appears as a small, shining, sago grain papule, but soon assumes the typical appearance of a sharply defined, rounded lesion, with a rough keratotic surface surrounded by a smooth collar of thickened horn. Most plantar warts are beneath pressure points, the heel or the metatarsal heads. Mosaic warts are so described from the appearance presented by a plaque of closely grouped warts. Pain is a common, but variable symptom.

Differential diagnosis is corn/s. • On paring, epidermal ridges are seen to continue without interruption in corns, whereas in warts epidermal ridges are interrupted on the surface of the wart.

Fig. 7.7: Common warts—rough surfaced keratotic papules over the dorsa of hand

Fig. 7.8: Plane warts—smooth surfaced papules over the face

Viral Infections planus causes most difficulty. Lichen planus favours the flexor aspects of the forearms, is unusual on the face and is often itchy. The mucous membranes may be involved. The flat polygonal papules are lilac-pink and smooth and may show Wickham’s striae. Filiform and digitate warts: Occur commonly in the male, on the face and neck. They are irregularly distributed, often clustered. Digitate warts often in small groups also occur on the scalp in both sexes where they are occasionally confused with epidermal naevi. Anogenital warts: It has been estimated that up to 30 to 50% of sexually active adults are infected with HPV, making it the most common viral STD in some STD clinics. Most of them occur on the penis, scrotum, urethral meatus and perianal area in men and on the introitus, vulva, perineum and perianal area in women. The four morphological types are— 1. Cauliflower like (condyloma acuminata) (Fig. 7.9) 2. Papular 3. Keratotic 4. Flat topped. Bowenoid papulosis: is a clinicopathologic entity in which HPVs (HPV-16 is the most

Fig. 7.9: Genital warts—cauliflower like lesion of condyloma acuminata over the glans penis along with herpes genitalis

common that has been linked to it) have been identified. These appear as 2 to 3 mm papules often multiple over the external genitalia. Histologically, there is cellular atypia resembling Bowen’s disease. Buschke Lowenstein tumor (giant condyloma): This lesion emerges from a preexisting benign anogenital wart before developing into a verrucous carcinoma. Usually, it is associated with type 6 and 11. Clinically, it resembles a large aggregate of condyloma acuminata over the glans penis (Fig. 7.10), foreskin, vulva or anal region. Epidermodysplasia verruciformis: Usually manifests in childhood with widespread warts. It is an inherited disorder in which there is wide spread and persistent infection with HPV giving rise to a combination of plane warts, pityriasis versicolor like lesions and reddish plaques (Figs 7.11 and 7.12). Multiple warts that do not resolve spontaneously, recur after treatment, persist for years, and have an unusual morphology may suggest epidermodysplasia verruciformis. Malignant change is very common but metastasis is rare.

Fig. 7.10: Buschke Lowenstein tumor—a large verrucous growth seen involving the glans penis

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Fig. 7.11: Epidermodysplasia verruciformis— pityriasis versicolor like lesions over the forearm

Fig. 7.12: Epidermodysplasia verruciformis—verruca vulgaris like lesions aggregating over the dorsa of the foot

Diagnosis • Clinical diagnosis of warts is often sufficient but atypical, subclinical or dysplastic lesions may need laboratory confirmation of HPV infection. • Other than histopathology of lesion (Koilocytosis in the stratum granulosum and stratum spinosum), detection of virus particles by electron microscopy, immunocytochemistry using type specific antibodies, DNA hybridization on tissue extracts and polymerase chain reaction may be done.

• Electrosurgery: Electrodesiccation or electrofulguration may be done. • CO2 laser ablation. • Cryotherapy: Either using liquid nitrogen using dipstick method or spray method, or nitrous oxide cooled probes. • Keratolytic agents like 10 to 20% salicylic acid topically may be used. • Formalin soaks with 2 to 3% formalin in water every day for 15 minutes is useful for plantar warts. • Curettage or surgical excision for warts unresponsive to topical treatment. • Topical retinoic acid for flat warts. • Cantharidin causes blistering and focal destruction of the epidermis. • Cidofovir and 5-FU topically. • Intralesional bleomycin. • Injection of 0.1 ml of 1:1000 candida antigen in the base of each wart. • Topical sensitizer and systemic immunomodulators (Interferon, especially interferon

Treatment Most common warts disappear spontaneously within 2 year or with simple nonscarring treatment. Commonly employed modalities of treatment are: • Chemical cautery: Trichloroacetic acid is used for common warts, filiform warts and plantar warts.

Viral Infections alpha intralesionally or intramuscularly) may be employed depending upon the condition. • Extensive warts, even in hitherto untreatable epidermodysplasia verruciformis, have improved or cleared with oral isotretinoin or etretinate. • Treatment of genital wart is discussed separately in STD section but salient treatment options are given below. 1. Podophyllotoxin 0.5% self administered twice a day for 3 days in week for 4 weeks or podophyllin 25% in tincture benzoin, once or twice weekly. 2. Liquid nitrogen cryosurgery 3. Electrosurgery 4. Surgical excision 5. Chemical cautery 6. Topical imiquimod.

HERPES SIMPLEX INFECTION • The word herpes is derived from the Greek, meaning, “to creep”. • The human herpes simplex virus consists of two closely related viruses designated herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). The virus causes a wide variety of mucocutaneous infections and produce both primary and recurrent infections. • HSV -1 is generally associated with oral infection, and HSV-2 is associated with genital infection. However, HSV-1 genital infection and HSV-2 oral infection are becoming common, as a result of oral-genital sexual contact and as most these infections are asymptomatic • Transmission of HSV infections most frequently occurs through close contact with a person who is shedding virus at a peripheral site, mucosal surface, in genital or oral secretions. • Neonates often have maternally acquired HSV-1 antibodies, which decline to low levels by 6 months of age.

Fig. 7.13: Primary herpetic gingivostomatitis—lips also involved along with oral cavity with vesiculation, erosions and hemorrhagic crusting

• Primary herpetic infection of the mouth and pharynx (Herpetic gingivostomatitis) is a disease of children (Fig. 7.13) and young adults. The peak years of incidence occur between age 1 and 5. The usual onset is with fever, sore throat, painful vesicles and ulcerative erosions. • The clinical manifestations of genital herpes should be differentiated into first clinical episode and recurrent episodes. The first clinical episode can further be sub-divided into primary infection, occurring in a person without prior HSV 1 or 2 antibodies (true primary) or nonprimary infection, occurring in a person with prior HSV 1 or 2 antibodies. The patients with first episode non primary have lower frequencies of systemic symptoms, shorter duration of pain, fewer lesions and a shorter healing time compared with the true primary infections. • Primary genital HSV-2 and HSV-1 infections (Herpes genitalis) are characterized by frequent and prolonged systemic and local symptoms. Fever, headache, malaise and myalgia are reported in 40% of men and 70% of women with primary HSV-2 infection. Widely spaced pustular or ulcerative lesions on the external genitalia are the most frequent presenting signs. Ulcerative lesions persist for 4-15 days until crusting or re-epithelization occurs.

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Fig. 7.14: Recurrent herpes labialis—erosions seen over the angle of mouth on one side

Fig. 7.15: Recurrent herpes genitalis—closely grouped vesicles over the shaft of the penis

• Recurrences occur in 30-50% of cases of oral herpes (Fig. 7.14) but are more frequent after genital herpes infection (Fig. 7.15), developing in 95% of those with type 2 HSV compared with 50% in type 1 infection. They are usually triggered by fever, respiratory tract infection, ultraviolet radiation, trigeminal neuralgia, dental surgery or dermabrasion. Recurrent infections differ from primary infection in the smaller size of the vesicles, their close grouping and absence of systemic symptoms. • Herpes simplex virus type 2 is now the most common cause of genital ulceration among the sexually transmitted diseases. • Complications seen are eczema herpeticum or Kaposi’s varicelliform eruption (Widespread vesicular HSV lesions that arise from primary or recrudescent infection in patients with several dermatoses, particularly atopic eczema.), neurological sequelae (Aseptic meningitis, autonomic dysfunction especially of the sacral dermatomes, rarely, transverse myelitis, Bell’s palsy, Guillain Barre syndrome may follow orolabial HSV infection), extra genital lesions (extra genital lesions is a common complication of first

episode primary genital herpes and is seen over buttock, groin, or thigh, although finger and eye can also be involved.), and disseminated infection. • Atypical HSV presentation occur relatively often in HIV – infected patients, particularly severe lesions occur over back, buttocks or perianal region and these may expand to over 20 cm in diameter. Chronic HSV-2 ulcers of more than 1-month duration are an AIDS – defining illness. HSV may also cause life threatening disseminated infection, esophagitis, hepatitis and pneumonitis in AIDS – patients.

Fig. 7.16: Herpetic whitlow—grouped vesicles over the great toe

Viral Infections

Fig. 7.18: Tzanck smear showing multinucleated giant cell

Diagnosis

Fig. 7.17: Eczema herpeticum—widespread vesicular eruption over the face in a patient with allergic contact dermatitis

Clinical Entities Caused by HSV-1 1. Primary herpetic gingivo-stomatitis 2. Herpes labialis 3. Traumatic herpes—herpetic whitlow (Fig. 7.16), herpes gladiatorum 4. Eczema herpeticum (Fig. 7.17) 5. Atypical presentations—Zosteriform herpes simplex, varicella like eruption, neurologic herpes simplex 6. Ocular herpes simplex (Herpetic keratoconjunctivitis) 7. CNS involvement 8. Disseminated herpes.

• The most reliable way to make a diagnosis is by viral culture. • A valuable clinical approach for making a rapid diagnosis is Tzanck smear. Smears of the bases of deroofed HSV vesicles are stained with Giemsa or Wright’s stain and examined by light microscopy for multinucleated giant cells (Fig. 7.18). • Primary infections can be diagnosed by seroconversion or a rise in antibody titer. Differential Diagnosis 1. For herpes gingivostomatitis- Diphtheria, thrush, aphthosis, streptococcal infections, and Stevens Johnson syndrome. 2. For recurrent herpes labialis-Aphthous ulcers, erythema multiforme, and impetigo.

Treatment Acyclovir has modified the treatment outcome.

Clinical Entities Caused by HSV-2

Primary Infection

1. Genital herpes 2. Recurrent lumbosacral herpes simplex 3. HSV infections in the newborn.

Herpetic gingivo-stomatitis— • Acyclovir 5 mg/kg body weight 8 hourly for 7 to 10 days.

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Recurrent Infection • Acyclovir 200 mg 5 times a day for 5 days or • Acyclovir 400 mg tds × 5 days or • Acyclovir 800 mg BD × 5 days Alternative antiviral drugs are famciclovir (125 mg, 250 mg twice daily) and valacyclovir (500 mg, 1 gm twice daily). For suppression of recurrences- Acyclovir 400mg twice a day for at least 1 year.

Treatment of Acyclovir Resistant Cases Include 1. Cidofovir: Unlike acyclovir, it is phosphorylated only by cellular enzymes, hence it is active against HSV with deficient or altered thymidine kinase enzyme. 2. Foscarnet: It is a phosphonate viral DNA polymerase inhibitor. It has been the preferred agent for patients with acyclovir resistant HSV infection.

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the sensory neurons following an earlier varicella attack. Both conditions are usually benign and selflimiting in patients with normal immunological status. One attack of varicella in childhood gives life long immunity to the patient. The incubation period is usually 14-17 days. Varicella occurs throughout the world, the highest incidence occurs in children aged 2-10 years. In tropical and semitropical countries, infection is delayed and varicella is seen more often in adults. Subclinical infection may occur. On the other hand, zoster is uncommon in childhood and the incidence increases with age. In patients with impaired immunity, both the incidence and severity of zoster are increased, and it is frequently complicated by disseminated cutaneous disease and systemic involvement, usually pneumonia, hepatitis, or encephalitis.

Vaccines: The precise role of vaccines in future management of HSV infection is yet to be determined. Modification of frequency and severity of recurrences may be achievable with vaccines. The most promising candidate vaccines are those based on HSV glycoproteins B and D.

VARICELLA-ZOSTER VIRUS INFECTION • Varicella (chicken pox) and herpes zoster are two distinct clinical entities caused by the same virus, varicella zoster virus (VZV). • Varicella is the primary exogenous VZV infection, while herpes zoster represents reactivation of an endogenous VZV infection, which persists in a latent form in

Fig. 7.19: Chicken pox—vesicular eruption over the trunk in different stages of evolution in an adult patient

Viral Infections usually by staphylococci or streptococci and may be prolonged by scarring. Other notable complications are primary varicella pneumonia, Reye’s syndrome, acute cerebellar ataxia, encephalitis, and disseminated varicella in immunosuppressed. • Maternal varicella during the early months of pregnancy can lead to ‘congenital varicella syndrome’, which manifests as extensive cutaneous scarring, muscular atrophy, limb hypoplasia, rudimentary digits, chorioretinitis and cortical atrophy. Fig. 7. 20: Chicken pox—dew drops on rose petals appearance

• In patients infected with HIV, zoster is 10 times more common than in normal population and may become disseminated and chronic.

Varicella • In older children and adults, the rash is often preceded by 2 to 3 days of fever, chills, malaise, headache, anorexia, severe backache and in some patients, sore throat and dry cough. • The rash of varicella begins on the face and scalp and spreads rapidly to the trunk (Fig. 7.19) with relative sparing of the extremities. • New lesions appear in successive crops but their distribution remains centripetal. • The lesion starts as a 2 to 4 mm red papule, which develops an irregular outline (rose petal) as a thin-walled clear vesicle appears on the surface (dew drop). This lesion, “dew drop on a rose petal” is highly characteristic (Fig. 7.20). The vesicles become umbilicated and pustular, rupture to form crusted lesions. • A distinctive feature of varicella is the simultaneous presence of skin lesions in all stages of evolution in any one area of the body. • The most common complication is the secondary bacterial infection of skin lesions

Differential Diagnosis of Varicella • Disseminated herpes simplex: Has concentration of lesions at and surrounding the site of the primary infection and there is associated marked toxicity and encephalitis. • Eczema herpeticum: Vesicles develop over the areas of active or recently healed atopic dermatitis. The lesions are particularly distributed on the face. Patients commonly have high fever and adenopathy. Zoster (Shingles) • The word ‘Shingles’ is derived from the Latin ‘singulus’ a girdle that refers to the segmental arrangement of the eruption.

Fig. 7. 21: Herpes zoster—grouped vesicles on erythematous patches in thoracic dermatome

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Fig. 7. 22: Herpes zoster—grouped vesicles on genitalia in a male

Fig. 7. 23: Herpes zoster ophthalmicus—unilateral involvement of forehead and scalp by herpes zoster

• Zoster afflicts 20% of the general population, during their life times, especially the elderly. • More than two thirds of the reported cases occur in individuals over fifty years of age and less than ten percent occur in those under the age of twenty years. • The first symptoms are usually pain and paraesthesia in the involved dermatome. This often precedes the eruption by several days and varies from superficial itching, tingling, burning or lancinating pain. • The rash is nearly always unilateral. • It begins as closely grouped maculopapules, which rapidly become vesicular in 12-24 hours (Figs 7.21 and 7.22) and then pustular in 2 to 3 days. The lymph nodes draining that area become enlarged and tender. The lesions dry up and crust in 7 to 10 days. Recovery takes about 3 to 4 weeks or longer in older patients. • The thoracic (53%), cervical (20%), trigeminal, including ophthalmic (18%) (Fig. 7.23) and lumbosacral (11%)

dermatomes are most commonly involved at all ages, but the relative frequency of ophthalmic zoster increases in old age. • Hutchinson’s sign: Vesicles on the side or on the tip of the nose that occur during episode of ophthalmic zoster are usually associated with serious ocular complications. • Complications of herpes zoster are hypopigmented or hyperpigmented scars, post herpetic neuralgia (usually defined as ‘chronic segmental pain’ appearing or persisting 3 months after cutaneous zoster healing), post herpetic anesthesia, recurrent zoster, motor neuron involvement (motor weakness usually follows the pain and eruption by a few days to weeks), ocular complications (superficial and deep keratitis, corneal ulcerations, panophthalmitis, ocular palsies, neuralgia, retinal vasculitis and optic neuritis), and rare complications include meningitis, pneumonitis, and myelitis. • Post herpetic neuralgia- Overall incidence is 8 to 15% and risk factors are old age, severe

Viral Infections • Skin biopsy of lesions also shows histological changes similar to those found in herpes simplex. • Definitive diagnosis accomplished by the isolation of virus in cell cultures and electron microscopy. • Identification of VZV antigens in cutaneous lesions and PCR for detection of nucleic acids in clinical specimen are the alternative methods of diagnosis.

Fig. 7.24: Herpes zoster—zoster occurring in multiple dermatomes

pain during acute phase, presence of prodromal pain, greater rash severity, and delay in starting treatment. • In HIV infected patients, herpes zoster ophthalmicus (HZO) is associated with several severe complications and may the initial manifestation of AIDS. Cutaneous lesions can be unidermatomal, multidermatomal (Fig. 7.24), disseminated or chronic and ulcerative. Differential diagnosis: Zosteriform herpes simplex- Vesicles vary in size in zoster, in contrast to uniformly sized vesicles in herper simplex and a history of multiple recurrences at the same site in herpes simplex.

Diagnosis • Tzanck smears of cutaneous lesions of varicella and zoster show multinucleated giant cells and epithelial cells with typical acidophilic intra-nuclear inclusions similar to those seen in herpes simplex.

Treatment • Symptomatic treatment is given in otherwise healthy patients. Rest and analgesics are advised. • Acyclovir is given in severe varicella and zoster (ophthalmic herpes zoster, Ramsay Hunt syndrome) and also in those patients who are at high risk of disseminated infection (more than 50 years of age, immunosuppressed patients). Acyclovir 800 mg 5 times a day for 7 to 10 days (in children dose is 20 mg per kg body weight four times daily). • Alternative antiviral drugs are famciclovir (500 mg three times daily), valacyclovir (1 gm three times daily) and foscarnet in acyclovir resistant cases. • Valacyclovir is contraindicated in immunosuppressed individuals. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome have occurred in patients with AIDS, renal transplant and bone marrow transplant. • For post herpetic neuralgia-topical therapy (capsaicin, aspirin, lignocaine), nerve blocks, and systemic therapy (systemic steroids, carbamazepine, valproate, tricyclic antidepressants) may be tried. Gabapentin is the drug of choice now. Initial dose of 300 mg/day is increased over 4 weeks (up to 3600 mg/day divided into three divided doses) until efficacy obtained or side effects tolerable.

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• Live attenuated viral vaccine for varicella can be used in healthy children as a prophylaxis. Its efficacy persists for 10 years. • Varicella zoster immunoglobin therapy is indicated in those who are high risk patients, to prevent or modify varicella in them.

KAPOSI’S VARICELLIFORM ERUPTION (ECZEMA HERPETICUM) •

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It is a special form of widespread cutaneous viral infection occurring in a patient with preexisting skin disease. Atopic eczema is the most common predisposing condition. Other susceptible dermatoses include Darier’s disease, pemphigus foliaceous, ichthyosis vulgaris, mycosis fungoides and allergic contact dermatitis (Fig. 7.17). Majority of cases are due to infections with herpes simplex virus – called eczema herpeticum. Less commonly occur with other viruses like Coxsackie A 16 and vaccinia (eczema vaccinatum- no more seen). Clinically presents with clusters of umbilicated vesicles in areas where the skin has been previously abnormal. They may be associated with fever and other constitutional features. The face is usually severely affected and may be edematous.

• The evolved pustules become crusted and heal with permanent scarring in 2-6 weeks. • Multinucleated epithelial giant cells are seen in Tzanck smear. • Treated with antiviral such as acyclovir where infection is due to herpes simplex virus.

KAWASAKI DISEASE (KD) KD is an acute multisystem vasculitis of unknown etiology. It was first described in Japan by Kawasaki (1967). CDC diagnostic criteria: Fever lasting longer than 5 days plus at least four of the following: 1. Bilateral conjunctival injection. 2. Mucous membrane changes (1 or more): Red or fissured lips, red pharynx, ‘strawberry’ tongue. 3. Extremity changes (1 or more): Erythema of palms or soles, edema of hands or feet, desquamation (generalized or periungual) 4. Rash-erythematous exanthema. 5. Cervical lymphadenopathy (at least 1 node larger than 1.5 cm). • Death in KD occurs due to cardiac complications. • Treatment: aspirin, intravenous gammaglobulin.

Fungal Infections

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Fungal Infections

Fungi are aerobic organisms that form a cell wall and grow on or in organic material, forming a colony and reproducing either sexually or asexually. In contrast to plants, fungi do not manufacture chlorophyll. Without photosynthetic capabilities, they are dependent on other life forms including human beings. Fungi are also essential part of the ecologic cycle and also of considerable benefit to man as a source of antibiotics, in baking and in beer brewing. Fungal infections of skin may be divided into superficial and deep.

Superficial fungal infections DERMATOPHYTE INFECTIONS (TINEA, RINGWORM) • Causative agent: The dermatophyte (or ringworm). Three species of dermatophytes implicated are: 1. Trichophyton (affects skin, hair and nails) 2. Microsporum (affects skin and hair) 3. Epidermophyton (affects skin and nails) Humans acquire infection from three sources— soil, animal or humans • Dermatophyte fungi grow only within keratin layers, do not invade living epidermis

• Predisposing factors—Tropical climate of heat and humidity, poor nutrition and hygiene, debilitating diseases including HIV infection • It occurs at any age except tinea capitis which occurs in children mainly. • Most common dermatophyte incriminated is Trichophyton rubrum Tinea corporis—infection of the non-hairy skin of trunk and limbs • The typical lesions start as itchy erythematous macule or papules that spread outward and develop into annular (ring like) and arciform lesions with sharp, scaling or papulovesicular advancing margin and healing centers (Figs 8.1 and 8.2) • A variant of tinea corporis called tinea imbricata (imbricata is Latin for tiled) caused by Trichophyton concentricum, is characterized by large concentric rings, one inside another, which manifest commonly in childhood. • Other variants. 1. Majocchi’s granuloma–characterized by perifollicular granulomatous nodules on the scalps of children, often without pustulation 2. Agminate folliculitis- characterized by well defined erythematous plaques

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Fig. 8.1: Tinea corporis–typical annular erythematous ring like lesions of tinea corporis

studded with perifollicular pustules caused by zoophilic organism. • Differential diagnosis: A. For annular lesions are nummular eczema (does not have an advancing border, lacks central clearing), granuloma annulare (no scaling, presence of skin colored intradermal papules) and erythema annulare centrifugum (have scales at the trailing edge of the advancing border instead of over the entire border). B. For papulosquamous lesions are psoriasis (well defined erythematous plaques, scales are silvery white micacaceous and reveal bleeding points when removed positive ‘Auspitz sign’, lesions typically involve extensor extremities, scalp and sacrum), pityriasis rosea (papular or annular, oval multiple lesions have characteristic distribution pattern over the trunk, individual lesions have a collarette of scales, scale does not reach the edge of the erythematous border, this acute eruption, has self limited course). Tinea cruris-ringworm of the groin (“jock’s itch” “Dhobi itch”) • Most common in the tropics (Fig. 8.3). • Differential diagnosis are candidiasis (more often involves concavities of the flexures and produces macerated, moist, glazed, erythematous plaques with satellite pustules and it

Fig. 8.2: Tinea corporis–multiple ring like lesions over the trunk

Fig. 8.3: Tinea cruris–marked hyperpigmentation with active border showing erythematous papules

more often involves the scrotum), inverse psoriasis (tends to be asymptomatic, welldefined erythematous plaque), and erythrasma (lacks a scaling border and inflammation, asymptomatic in nature, fluoresces coral red under a wood light).

Fungal Infections

Fig. 8.4: Tinea faciei–erythematous scaly annular lesion over the face

Tinea barbae-ringworm of the beard and moustache. Tinea faciei-ringworm of the face- most often misdiagnosed (Fig. 8.4). Tinea capitis- ringworm of the scalp, transmitted from child to child, most commonly caused by Trichophyton violaceum. In the western literature, commonest causative organism recorded is T. tonsurans. Both of them cause endothrix infection (arthroconidia of dermatophytes contained within the hair shaft) of hair. Less frequently, ectothrix infection (arthroconidia of dermatophytes surrounding the hair shaft as a sheath) of hair also occurs. • Patchy hair loss and broken hairs, inflammation and scaling are characteristic of (back dot (Fig. 8.5), grey patch (Fig. 8.6), seborrheic dermatitis like) tinea capitis. • Kerion is caused by zoophilic fungi– Trichophyton verrucosum and Trichophyton mentagrophyte. Typically, it produces a boggy painful inflammatory swelling studded with exudative follicular pustules, hair fallen off or easily pluckable (Fig. 8.7). • Favus in India occurs mainly in Kashmir and is caused by Trichophyton schonleinii. On the scalp, concave sulfur-yellow crust (called scutulae) form around loose wiry hairs. It heals with thin smooth atrophic scarring.

Fig. 8.5: Tinea capitis–patchy hair loss with black dots “Black dot” type

Fig. 8.6: Tinea capitis–partial loss of hair, remaining hair in the alopecia patch area are luster less “Grey patch” type

Differential diagnosis are alopecia areata (patchy non-scarring alopecia, presence of exclamation mark hair, non-scaly condition), trichotillomania (irregular patchy hair loss from an approachable site because of hair pull trauma, so hairs are of different lengths), seborrheic dermatitis (greasy scaling is more diffuse, with erythema, changes confined to scalp and other

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Fig. 8.7: Tinea capitis–boggy inflammatory swelling over the scalp “Kerion” type

Fig. 8.8: Tinea pedis–scaly hyperkeratotic lesion on the sole of one foot, other normal for comparison

seborrheic areas of the body, generally no hair loss), and bacterial pyodermas of scalp (loss of hair is minimal, plucking of hair may be difficult and painful)

keratodermas and hyperkeratotic eczema. Contact dermatitis may also be considered although it affects the dorsum of foot than plantar aspect (tinea pedis). The vesicobullous type may be confused with pustular psoriasis, palmoplantar pustulosis, and bacterial pyodermas.

Tinea pedis- ringworm of the feet (“Athlete foot”) • Interdigital type-interdigital scaling and maceration with fissures is the most common form (Fig. 8.8). • Chronic hyperkeratotic type or Moccasin footwidespread scaling extends onto the sides of the feet. • Vesicular or bullous type due to some zoophilic fungi • Acute ulceratic type Differential diagnosis: For the interdigital type are erythrasma (very well defined lesion, it has whitish appearance usually asymptomatic and rarely causes fissures) and candidiasis (increased severity of maceration, denudation and pruritus). The hyperkeratotic type must be differentiated from palmoplantar psoriasis, palmoplantar

Tinea manuum-ringworm of the hands • Usually seen as mild erythema with hyperkeratosis and scaling, mainly over the palmar surfaces (Fig. 8.9). • Unilateral scaling with onychomycosis if present should always be scraped for fungus (Fig. 8.10). • Contact dermatitis, psoriasis, and hyperkeratotic eczema must be considered as differential diagnosis. Tinea unguium- fungal infections of the nails • Nail infection starts at the free margin or lateral borders of the nails, as yellow discoloration and progress proximally (distal and lateral subungual onychomycosis).

Fungal Infections

Fig. 8.9: Tinea manuum–unilateral scaly lesions of the palm

Fig. 8.11: Tinea unguium–thickening and dystrophy of involved nails

infection caused by dermatophytes that cause endothrix scalp infection characterized by scarred nail plate with pits and lamellar splits). • Ringworm of the nails is rarely symmetrical and it is common to find the nails of only one hand affected) • Differential diagnosis is psoriasis (coarse pitting of dorsal nail plate is never produced by fungal infection, and strongly suggests psoriasis, as does the oil drop sign from the free edge), eczema (irregularly buckled nails) and lichen planus (ridged or dystrophic nails) Tinea incognito- ringworm infections modified by corticosteroids, systemic or topical, prescribed for some pre-existing pathology or given mistakenly for the treatment of misdiagnosed tinea (Fig. 8.12). Fig. 8.10: Tinea manuum with tinea unguium

• The nails become brittle, friable, and thickened (Fig. 8.11). • Four distinct patterns of tinea unguium are distal and lateral subungual onychomycosis (most common pattern), superficial white onychomycosis, proximal subungual onychomycosis (associated with HIV/AIDS cases), and endonyx onychomycosis (nail

Diagnosis • KOH mount– definitive diagnosis is made by the microscopic examination and identification of hyphae and spores in scales (Fig. 8.13) or hair. In nails, the presence of hyphae usually means dermatophyte infection, rarely saprophytic fungi infection. • Cellophane tape examination and staining with periodic acid Schiff’s (PAS) reagent of

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Fig. 8.12: Tinea incognito–erythematous papular eruption of tinea due to immunosuppression

Fig. 8.14: Periodic Acid Schiff’s (PAS) stained smear showing septate branching hyphae–dermatophytes

2. Imidazole derivatives – miconazole (2%), clotrimazole (1%), econazole (1%), ketoconazole (2%), oxiconazole, sulconazole, eberconazole 3. Ciclopirox olamine 4. Undecylenic acid 5. Tolnaftate 1% 6. Azelaic acid 7. Castellani’s paint 8. Terbinafine (1%) Fig. 8.13: KOH mount–showing branching septate hyphae

the material taken from skin (Fig. 8.14), hair and nails can be studied. • Confirmed by culture on Sabouraud’s media. • Histological examination of nails with special stain-Periodic Acid Schiff’s stain.

Therapy • Topical therapy- indicated for infections of the body and groin and superficial involvement of the beard region, palms, and soles Topical agents used are— 1. Whitfield ointment (contains 6% benzoic acid and 3% salicylic acid)

Duration of therapy is 4 to 6 weeks or 2 weeks more after clearance of lesions. • Systemic therapy– required in case of hair and nail infection and in those cases where tinea is extensive, widespread and non-responsive to topical therapy. Griseofulvin (10-20 mg per kg body weight or 250 mg twice a day), ketoconazole (200 mg daily), itraconazole (200 mg daily or one week pulse of 400 mg daily for 2 to 3 months), fluconazole (6 to 8 mg per kg body weight daily or 150 mg, 300 mg or 450 mg per week for 3 to 6 months) and terbinafine (250 mg daily or 250 mg twice a day) are the drugs used systemically. The skin and hair infection require shorter course of therapy (6-8 weeks therapy with griseofulvin) whereas nail infection require longer therapy (9-12 months with griseofulvin).

Fungal Infections

TINEA VERSICOLOR (PITYRIASIS VERSICOLOR, DERMATOMYCOSIS FURFURACEA, CHROMOPHYTOSIS) • It was thought that a single polymorphic yeast Pityrosporum ovale, or two species P. ovale and P. orbiculare, were the causative agents, but it is now recognized that this genus was invalid. There are at least 7 separate species of lipophilic yeast- Malassezia on the human skin: M-sympodialis (most commonly found on the normal skin), M.globosa (most frequently associated with tinea versicolor), M. restricta, M. dermatis, M.slooffiae, M.obtusa and M. furfur. • Predisposing factors- Warm and humid climate of tropics, pregnancy, serious underlying diseases, immunocompromised host, Cushing’s syndrome, malnutrition. • The term “versicolor” refers to the presence of both hyper-and hypopigmented lesions • A peculiar aspect of tinea versicolor is its propensity to present as either hypopigmented or hyperpigmented, finely scaling, round or perifollicular coalescing macular patches found primarily over the trunk (Figs 8.15 and 8.16). The hypopigmentation is explained on the basis of dicarboxylic acids produced by Malassezia species (e.g., azelaic acid) causing competitive inhibition of tyrosinase and perhaps a direct cytotoxic effect on

Fig. 8.15: Tinea versicolor–hypopigmented macules with fine powdery scales

Fig. 8.16: Tinea versicolor–hyperpigmented macules with fine scaling

hyperactive melanocytes. The hyperpigmentation may be due to abnormally large melanosomes and thicker keratin layer. To elicit fine branny powdery scales, candle grease sign or coup d’ongle sign is elicited. • The eruption is almost always asymptomatic and only of cosmetic significance • Other cutaneous disorders associated with Malassezia yeasts are seborrhoeic dermatitis, Malassezia folliculitis, Confluent and reticulate papillomatosis, and sebopsoriasis.

Diagnosis • KOH preparation-reveals numerous short, straight and angular hyphae and clusters of thick walled round and budding yeasts “Spaghetti and meat ball appearance” or “Banana and grapes appearance”(Fig. 8.17). • Cellophane tape examination and staining with periodic acid Schiff’s (PAS) reagent and India ink of the material taken from skin (Figs 8.18 and 8.19).

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Fig. 8.17: KOH mount–clusters of spores with short mycelial filaments. “Spaghetti and meat ball” appearance

Fig. 8.18: Periodic Acid Schiff’s (PAS) stained smear showing cluster of spores with short stumpy mycelial filaments- Malassezia

• Culture- Sabouraud’s dextrose agar overlaid with sterile olive oil or lanolin. Antibiotics such as penicillin, streptomycin and cycloheximide are incorporated to reduce growth of contaminants. • Wood’s light examination-golden to orange fluorescence.

Differential Diagnosis 1. Pityriasis alba– characterized by poorly marginated, hypopigmented, slightly scaly patches on the cheeks of young children.

Fig. 8.19: Parker ink staining of hyphae and spores of tinea versicolor

2. Indeterminate leprosy– usually seen in children with one or more macules, hypopigmented to faintly erythematous with an ill-defined to well defined edge. Lesions may be on the face or the limbs. Slight anaesthesia may be demonstrable. 3. Vitiligo– characterized by depigmented macules without any scaling 4. Erythrasma– Hyperpigmented tinea versicolor can be confused with erythrasma, but satellite lesions are less common in erythrasma and there is coral red fluorescence under Wood’s lamp. 5. Seborrhoeic dermatitis– May occur in areas of tinea versicolor distribution, but patches have an erythematous yellowish tint and scales are soft and greasy

Therapy – Topical– Selenium sulfide suspension (2.5%), zinc pyrithione, ketoconazole (2%) shampoo, sodium hyposulfite (25%), propylene glycol and imidazole derivatives are used topically. – Systemic– Ketoconazole (200 mg daily for 5 to 10 days), itraconazole (200 mg daily for 5 to 7 days) or fluconazole (single oral dose of 400 mg) are effective systemically.

Fungal Infections

CANDIDIASIS –

–

Causative agent –Candida albicans. This yeast like fungus is normally found on the mucous membranes, skin, in the gastrointestinal tract and in the vagina. Under certain circumstances, it changes from a commensal organism to a pathogen. Apart from Candida albicans, few other species of Candida like C. tropicalis, C. dubliniensis, C. parapsilosis, C. guilliermondii, C. krusei, C. glabrata may be involved Predisposing factors– Local factors are moisture, warmth, maceration, and/or occlusion and systemic factors are antibiotics therapy, corticosteroids, oral contraceptive pills, pregnancy, diabetes, immunocompromised state including HIV infection.

can be confused with coated tongue due to dehydration, mucositis due to chemotherapeutic drugs, aphthous ulcerations, herpetic infections, oral hairy leukoplakia, erythema multiforme, pemphigus, lichen planus, discoid lupus erythematosus, Pernicious anemia, histoplasmosis, leukoplakia, secondary syphilis. • Perleche–sore angles of mouth. • Intertriginous type– Well-defined peeling border around moist red macerated lesions and surrounded by satellite papules or pustules- occur in body folds such as groin, inframammary, axillary, perianal and interdigital areas (Fig. 8.22). Differential

Clinical Manifestations • Oral thrush– It presents as curdy, white, easily detachable deposits on tongue or oral mucosa with underlying bright red and moist surface (Figs 8.20 and 8.21). This form of candidiasis is also known as acute pseudomembranous candidiasis. It is the most common form of oral candidiasis. Other forms of oral candidias is include acute and chronic atrophic candidiasis, chronic hyperplastic candidiasis, and median rhomboid glossitis. Oral thrush

Fig. 8.21: Oral candidiasis with angular cheilitis in a HIV adult case

Fig. 8.20: Oral candidiasis–curdy white deposits on the hard palate in a baby

Fig. 8.22: Intertriginous candidiasis–toe cleft showing moist macerated lesion

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Essentials in Dermatology diagnosis includes tinea cruris, seborrhoeic dermatitis, flexural psoriasis and bacterial intertrigo. • Paronychia– inflammatory boggy swelling of posterior and lateral nail folds of digits of fingers (Fig. 8.23), commonly seen in house wives, maidservants, due to continuous wet job • Vulvovaginitis-frequently associated with itching and vaginal discharge. The vaginal mucosa shows erythema, edema and curdy white deposits (Fig. 8.24). Candidal balanoposthitis occurs as a counter part in males (Fig. 8.25).

Fig. 8.25: Candidal balanoposthitis–glazed erythema with pustulation over glans and prepuce

Diagnosis • KOH preparation-reveal budding yeasts with or without hyphae or pseudohyphae. • Gram’s stained smear-gram positive organisms longer than bacteria. • Confirmed by culture on Sabouraud’s media. Whitish mucoid colonies grow within 2 to 5 days.

Fig. 8.23: Chronic paronychia–swelling of proximal and lateral folds of many fingers with nail changes

Fig. 8.24: Candidal vulvovaginitis–vulval erythema with white deposits

Therapy • Evaluation and treatment of underlying medical conditions • Nystatin, imidazoles and broad-spectrum triazoles are the agents of greatest use in the treatment of candidal infection. Gentian violet and Castellani’s paint are older effective topical remedies. • Potassium permanganate soaks are more effective in moist Candidal intertrigo. • Recurrent or recalcitrant infections require oral medication with nystatin (to rid the gut and vagina of candida organisms), fluconazole (50 mg daily for 14 days), ketoconazole (200 mg daily) or itraconazole (200 mg daily). • For vaginal candidiasis, 500 mg clotrimazole vaginal tablet once or 200 mg miconazole tablet at bed time for 3 days or single oral dose

Fungal Infections of 150 mg of fluconazole or twice daily dose of itraconazole (200 mg twice a day).

CHRONIC MUCOCUTANEOUS CANDIDIASIS • It is a rare syndrome which is characterized by recurrent and persistent candidal infection of skin, nail and mucous membrane. It has autosomal dominant or recessive inheritance. Several endocrinopathies (e.g. hypothyroidism, hypoadrenatism, etc.) may be associated. • Treatment: Treatment of this condition depends critically on systemic antifungal chemotherapy. Attempts have been made to restore T cell function, by the use of transfer factor, or thymosin, or grafting compatible T lymphocytes and non specific measures like the restoration of normal iron stores. Prolonged and repeated use of systemic antifungals like fluconazole, itraconazole and ketoconazole may be necessary.

PIEDRA (PIEDRA = STONE) (TRICHOSPOROSIS) • Causative agent– White piedra-Trichosporon beigelii (Trichosporon cutaneum), a yeast seen in temperate region – Black piedra-Piedra hortae, a mould, occurs mostly in the tropics • Pinhead sized, hard nodes occurs on the hairs of the scalp, brows, lashes, or beard • KOH examination and culture clinch the diagnosis • Differential diagnosis– Nits, hair casts, developmental hair defects and trichomycosis axillaris may be differentiated by doing a microscopic examination. • Treatment is by cutting hair. Oral terbinafine 250 mg daily for 6 weeks has been shown to be effective against black piedra. For white piedra, imidazoles, selenium sulfide, zinc pyrithione, etc. are effective agents.

Deep fungal infections

TINEA NIGRA

MYCETOMA

• Causative agent- Phaeoannellomyces werneckii (syn. Exophiala werneckii), a mould which produces a melanin like pigment. • This characteristic disorder manifests as one or several brown or black spots that resemble silver nitrate or India ink stains. • Most frequently lesions occur on the palms but also on the soles. • The fungus can be easily demonstrated by KOH examination and culture. • Differential diagnosis are junctional naevi, melanoma, Addison’s disease, and chemical stains, however, tinea nigra can be easily differentiated by doing a KOH examination which shows brown coloured hyphae and spindle shaped yeast cells. • Topical imidazoles such as clotrimazole, miconazole, ketoconazole, etc. are effective.

• Mycetoma is a deep fungal infection, characterized by a clinical triad of swelling, discharging sinuses and discharge containing granules (Figs 8.26 and 8.27). It commonly occurs on the foot, hence also called as Madura foot. • Mycetoma-caused by species of fungi is known as eumycetoma, and that caused by aerobic actinomycetes or filamentous bacteria as actinomycetoma. Type of mycetoma Causative organisms Eumycetoma

Actinomycetoma

Madurella mycetomatis Exophila jeanselmei Pyrenochaeta romeroi Fusarium species Actinomadura madurae Nocardia brasilensis Actinomadura pelletieri

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Fig. 8.26: Mycetoma–a triad of features – swelling, discharging sinuses and discharge containing granules seen commonly over the foot

• Differential diagnosis 1. Chronic osteomyelitis of bacterial or tuberculosis origin (characteristic grains are not discharged) 2. Elephantiasis (no sinus tracts) 3. Primary cutaneous actinomycosis (develops on the exposed sites, very rare type of actinomycosis, caused by Actinomyces isralei, a normal inhabitant of human mouth, thus it is an endogenous infection). • Actinomycetomas generally respond to antibiotics such as a combination of dapsone with streptomycin or sulfamethoxazoletrimethoprim plus rifampin or streptomycin. Amikacin may also be used in recalcitrant Nocardia infections. • Of the fungal causes of mycetoma, M. mycetomatis may respond to ketoconazole (200 mg daily over several months). For the others, a trial of therapy with griseofulvin or itraconazole is worth attempting. Surgery, usually amputation, is the definitive procedure and may have to be used in advanced cases.

CHROMOMYCOSIS (CHROMOBLASTOMYCOSIS)

Fig. 8.27: Mycetoma over the upper back

• The organisms are usually soil or plant saprophytes that are only incidental human pathogens. • KOH examination, Gram’s staining, histopathology of lesion and culture helps in confirmation of the diagnosis.

• Chromoblastomycosis is primarily a disease of tropical or subtropical regions. • At least five distinct organisms are well known to cause chromoblastomycosis: Fonsecaea pedrosoi, Fonsecaea compactum, Cladosporium carrionii, Phialophora verrucosa, and Rhinocladelia (Acrotheca) aquaspersa. • The characteristic feature of a well-developed lesion is a pruritic warty plaque of the extremities in an agricultural worker, which drains purulent material (Fig. 8.28). • The pathology of chromoblastomycosis consists of striking epidermal thickening (pseudoepitheliomatous hyperplasia) over-

Fungal Infections

Fig. 8.28: Chromomycosis–verrucous itchy plaque lesion over the dorsa of the hand

Fig. 8.29: Rhinosporidiosis–pink friable polypoidal growth projecting from the nares

lying a suppurative granulomatous dermatitis. At least three appellations are frequently used to designate the tissue form of these fungi: Medlar bodies, sclerotic bodies, muriform bodies or the descriptive “copper pennies”. • Differential diagnosis: 1. Blastomycosis (presence of sharp border with minute abscesses and by the presence of pulmonary lesions) 2. Cutaneous tuberculosis and leishmaniasis (biopsy and culture will establish the diagnosis) 3. Elephantiasis verrucosa nostras (mossy foot). • The known treatments may be divided into three groups: surgery, physical modalities (heat, cryotherapy, electrosurgery, and radiation therapy), and systemic antifungal medications(amphotericin B, 5-fluorocytosine, triazole derivatives especially itraconazole, and thiabendazole).

• It is seen most often in southern India and Srilanka. • It is more common in adult males and is possibly transmitted to man by direct contact with spores through dust, infected clothing or fingers and swimming in stagnant waters. • Rhinosporidiosis frequently involves the nasopharynx (70%) presenting as a painless, friable, polypoidal growth, which may hang, anteriorly from the nares (Fig. 8.29) or posteriorly into the pharynx. The lesions are pink or purple red and studded with minute white spots which are the sporangia containing spores. Nasal obstruction and bleeding are the most common symptoms. The conjunctiva and lacrimal sac are involved in 15% of cases. • Occasionally, it affects the lips, palate, uvula, maxillary antrum, epiglottis, larynx, trachea, bronchus, ear, scalp, vulva, vagina, penis, rectum or the skin (Figs 8.30 and 8.31). • Since the causative agent cannot be cultured, the diagnosis can be confirmed by demonstrating typical sporangia and spores in histopathology and imprint smears. • Differential diagnosis is nasal polyps, warts, and condylomas.

RHINOSPORIDIOSIS • Rhinosporidiosis is a chronic granulomatous mycosis caused by Rhinosporidium seeberi.

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Fig. 8.30: Rhinosporidiosis–pink friable polypoidal growth over the root of the nose

Fig. 8.32: Subcutaneous phycomycosis–shiny disk like indurated lesion over the thigh, can be insinuated at the margin with fingers

Fig. 8.31: Rhinosporidiosis–noduloplaque lesions over the arms

• Surgical removal and electro desiccation are the treatments of choice.

SUBCUTANEOUS ZYGOMYCOSIS • Subcutaneous zygomycosis or subcutaneous phycomycosis (SP) has two clinically and mycologically distinctive entities termed as basidiobolomycosis (etiological agent: Basidiobolus ranarum) and conidiobolomycosis (etiological agent: Conidiobolus

coronatus). These organisms belonging to Entomophthorales cause granulomatous infection that usually affects healthy people. • SP due to Conidiobolus is uncommon. Clinically, the disease is characterized by nasal obstruction due to the inflammation of the submucosa of the nostril, usually in the vicinity of the inferior turbinate. • SP is also caused by Basidiobolus. The site of infection is usually confined to the limb girdles or proximal limbs. It occurs chiefly in children. Characteristically, it manifests as painless, well-circumscribed, firm to hard subcutaneous masses, which grow slowly at the periphery and may envelop parts of or a whole limb (Fig. 8.32). The border is smooth, rounded, clearly defined, and can be raised up by inserting fingers underneath it. This is thought to be an almost diagnostic clinical feature of the disease. There is no involvement of the regional lymph nodes.

Fungal Infections • Differential diagnosis: 1. Lymphatic edema (no distinctive edge) 2. Subcutaneous malignant lymphoma (grows more rapidly) 3. Subcutaneous morphea • A therapeutic trial with potassium iodide in a clinical setting may be considered as an important criterion for diagnosis where facilities to culture the organism do not exist.

SPOROTRICHOSIS • It is caused by Sporothrix schenckii and is characterized by nodulo-ulcerative and crusted lesions arranged in a linear fashion over the extremities with intervening lymphatics thickened like a cord. • The best sources of diagnostic material are smears, exudates, and biopsies (to look for “Asteroid bodies”). S. schenckii is very rarely seen in direct microscopic examination because yeasts are usually present only in small numbers; the organism can be readily isolated on Sabouraud’s agar. • Differential diagnosis: 1. Fish tank granuloma 2. Cutaneous leishmaniasis • Potassium iodide (saturated solution) is effective in the cutaneous types of sporotrichosis. Other deep fungal infections: Cryptococcosis and aspergillosis are ubiquitous throughout the world. In south east Asia, penicillinosis is common whereas coccidioidomycosis and histoplasmosis are restricted to certain geographic regions.

CRYPTOCOCCOSIS • Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans.

• Virtually all infections involve the central nervous system, with meningitis the most frequent manifestation. • Cutaneous dissemination occurs in 10% to 20% of patients, has a variable presentation and may precede other signs of infection. • Initial signs of cryptococcosis include cellulitis, genital or oral ulcerations, or molluscum-, herpes simplex-, or Kaposi’s sarcoma- like lesions. • Diagnosis can be made by performing curettage on a lesion, by making a potassium hydroxide preparation, India ink preparation, isolation of fungus on culture or by a biopsy of lesion. Cryptococcal antigen is present in these patient sera and can be detected by latex particle agglutination. • Intravenous amphotericin B alone or with flucytosine and oral fluconazole is highly effective in the treatment of cryptococcus infection.

PENICILLIOSIS • Penicillium marneffei is the only penicillium species that is dimorphic and can cause systemic mycosis in human beings, particularly those who are immunocompromised. • Features of the infection frequently include fever, anemia, marked weight loss, cough and diarrhea, but skin eruptions occur in the majority. • Cutaneous manifestations usually consist of a generalised papular eruption, in which the papules may be umbilicated (due to central necrosis), although necrotic papules, nodules, folliculitis, macular rash and mouth ulcer have also been reported. • Diagnosis depends on isolation of the organism from blood or tissue. • Treatment includes systemic amphotericin B, itraconazole or fluconazole.

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9

Infestations

• Causative agent: Sarcoptes scabiei var. hominis (Fig. 9.1) • Morphology: The mite has an ovoid body, flattened dorsoventrally. The body is creamy white marked with transverse corrugations, and on its dorsal surface by bristles and spines (denticles). The mite has four pairs of short legs. The rear two pairs of legs of female mites end in long bristles called setae. Adult female mite measures about 0.4 × 0.3 mm whereas adult male about 0.2 × 0.15 mm. The mite prefers non-hairy skin and areas of low sebum production.

• Life cycle: Copulation occurs in burrows excavated by female mite in stratum corneum. After copulation, the pregnant female enlarges the burrows and begins egg laying. It travels 5 mm per day and lays 4050 eggs during its life span of 4-6 weeks (Figs 9.2 and 9.3). These eggs hatch in a week and reach maturity (eggs-larvae-nymph-adult) in about 3 weeks. • Most infected adults harbor 10 to 12 mites • Mode of spread-close personal contact, but may be transmitted through clothing, or towels. • Incubation period- when a human is infested for the first time, symptoms usually

Fig. 9.1: Sarcoptes scabiei mite (300-400 microns)

Fig. 9.2: Eggs and fecal pellets of sarcoptes

SCABIES (THE ITCH, SEVEN YEAR ITCH)

Infestations

Fig. 9.3: An egg of sarcoptes

Fig. 9.5: Scabies – periumbilical papular lesions

Fig. 9.4: Scabies – typical finger web spaces involvement with papular, vesicular and crusted lesions

Fig. 9.6: Scabies – genital and thigh area involved by papular and excoriated lesions

develop after 3-6 weeks while after reinfestation, they occur within 1 or 2 days. • The classic symptom is intense pruritus especially at night in bed • The sites of predilection are the interdigital spaces (Fig. 9.4), wrists, points of elbows, antecubital fossae, the anterior axillary folds, the umbilicus (Fig. 9.5), and the genitalia (Fig. 9.6) especially the gluteal cleft (Fig. 9.7) (“circle of Hebra”). • The most diagnostic or pathognomonic finding is an intact “S” shaped or linear burrow with a papule or vesicle at its end housing the mite (Fig. 9.8). Most common

Fig. 9.7: Scabies – papular lesions over the gluteal area

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Fig. 9.8: Scabies—typical burrows of scabies of the shaft of the penis

•

•

•

•

sites are webspaces of the hands, wrists, and lateral aspect of palms. Generalized urticarial papules, excoriations and eczematous changes are secondary lesions caused by sensitization to the mite. Tiny scaly papules on the nipple and male genitalia (glans, shaft and scrotum) are pathognomonic of scabies. Infants and small children often have vesicular lesions on the palms, soles, head and neck (Figs. 9.9 and 9.10). Scabies in babies is generally more extensive in distribution of burrows, vesicular or vesicopustular lesions on the hands and feet, extensive eczematization, multiple crusted nodules on the trunk and limbs. Nodular scabies- in some cases, itching nodules (5–20 mm in diameter, red, pink, tan or brown in color) persist for several months. They are found most commonly on the scrotum (Fig. 9.11). Burrow may be seen on the surface of early nodules.

Fig. 9.9: Scabies in an infant—papulovesicular lesions in finger web spaces

Fig. 9.10: Scabies in an infant – vesicular, pustular and crusted lesions on the ankle and feet

• Scabies incognito means modified clinical picture of classical scabies which mimic other dermatoses due to inappropriate use of topical steroids. • Complications of scabies: Secondary infection of skin lesions, eczematization, nephritogenic strains of streptococci may produce secondary sepsis, and glomerulonephritis particularly in tropics.

Infestations

•

Fig. 9.11: Nodular scabies—nodules seen over the scrotum

• Diagnosis: If a mite is demonstrated, one needs no diagnostic criteria. Typical lesions on the penis and nipple, the presence of burrows even without a mite and interdigital lesions are almost diagnostic. Severe pruritus, especially at night, of short duration or in family members is also very suggestive. • Burrow identification (Ink method): The suspected burrow is smeared with blue or black fountain pen ink and then wiped off with an alcohol swab after some time. The dye that enters the burrows is highlighted as a dark line. • Microscopic examination: The burrow is scraped with 15 no. blade and examine the material with 10% KOH or mineral oil under light micrscope. Presence of mite, egg or fecal concretions (scybala) confirms diagnosis of scabies. • Under dermoscope, mite in burrow resembles “jet with contrail”. • Differential diagnosis: A. For pruritic localized or generalized rash: In infants: Papular urticaria, infantile acropustulosis, In children: Papular urticaria, insect bite reactions,

• • • •

atopic dermatitis, animal scabies, In adults: acute generalized lichen planus, adverse drug reactions, contact dermatitis, pediculosis pubis, pediculosis corporis, different forms of prurigo, In elderly: Dermatitis herpetiformis, senile pruritis, delusional parasitosis. B. For pruritic nodules: Urticaria pigmentosa, papular urticaria (insect bite), and pseudolymphoma. Therapy: Permethrin (5%) cream is treatment of choice (single overnight application below neck all over the body with a second application after an interval of a week). It is the treatment of choice for infants (application includes head and neck also). Sulfur and crotamiton are safe in pregnancy. Other agents used are gamma benzene hexachloride lotion (1%), benzyl benzoate lotion (12.5% for infants and children, 25% for adults), esdepallethrine 0.63%, malathion 0.5% lotion, ivermectin 0.8% lotion, and monosulfiram (25%) diluted with two or three parts of water to form an emulsion. Ivermectin 200 microgram per kg body weight single oral dose is also effective in many cases of ordinary scabies, but presumably because of lack of ovicidal activity, higher cure rates are obtained with two doses separated by an interval of a week. It is a useful modality of treatment for institutional outbreaks of scabies as it is cheap, effective and easy to administer. Pruritus may persist for up to 1-2 weeks after the end of effective treatment. Treat infested individuals as well as close physical contacts simultaneously. Bedding and clothing should be washed in hot cycle of washing machine. Intralesional triamcinolone 5-10 mg / ml in each lesion is used for nodular scabies besides routine scabies treatment.

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CRUSTED SCABIES (NORWEGIAN SCABIES) • Very uncommon variant of scabies. • Though the first report of crusted scabies was in patients with leprosy, recent reports have described an increasing incidence of this form of scabies in patients with immunosuppression due to immunosuppressive agents, malignancy or acquired immunodeficiency syndrome (AIDS). • In this form of scabies, the host’s response to the mites is modified, allowing them to multiply. As a result of this, the mite population becomes enormous and may number millions. • The large adherent crusts are most often seen over the knees and elbows as well as the hands (Fig. 9.12) and feet. There may even be an erythroderma. • Frequently, it can be confused with psoriasis, chronic eczema (contact dermatitis), Langerhans cell histiocytosis, or neurodermatitis (Fig. 9.13). • Ivermectin seems to be ideal drug for this condition; otherwise prolonged therapy with topical scabicidal agents is required. Methotrexate is another option.

Fig. 9.12: Crusted scabies – hyperkeratotic scaly lesions over the palm and finger web space

Fig. 9.13: Crusted scabies—scaly cursted lesions over the side of the buttock

ANIMAL SCABIES • Contracted from pet animals-cats, dogs, or birds. • No burrows seen, only itching and papulovesicular lesions are seen over the site of contact-abdomen, thighs and arms. • Treatment of pet animal with scabicidal agent and antipruritic agents for controlling itching are required. • Human skin lesions are self limiting; resolve spontaneously if further contact with affected animal is stopped.

Fig. 9.14: Pediculus humanus capitis

Infestations

Fig. 9.15: Phthirus pubis

are oval, 1 mm long and firmly attached to the hair (Fig. 9.16) (or seems of clothing), hatch in about 7-9 days and become mature in another week. • Body louse is the vector for the following organisms: 1. Rickettsia prowazekii (Endemic typhus), 2. Bartonella quintana (Trench fever), 3. Borrelia recurrentis (Relapsing fever). • Extreme pruritus is the primary characteristic of pediculosis. • Incubation period—It takes 6 weeks (approximately 30 days) for the pruritus to develop in non-sensitized individual and only 24 to 48 hours with repeat exposures.

Pediculosis Capitis • Most common in children especially girls with long hairs. • Mode of spread- human to human contact or sharing combs, brushes and towels. • Scalp-favorite site is area behind the ear (Fig. 9.17) or occiput. • Nits may be found most easily on the hairs. Adult lice often impossible to find. • In patients with scalp pruritus, secondary pyoderma (with cervical lymphadenopathy) and dermatitis, one should always search the

Fig. 9.16: Nits attached to the hair

PEDICULOSIS (LICE INFESTATION) • Pediculus humanus capitis (2 to 4 mm long)head louse (Fig. 9.14). • Pediculus humanus corporis-body louse. • Phthirus pubis-pubic louse (Fig. 9.15). • Life cycle— these wingless six legged blood sucking insects are obligate parasites specific for humans, lays eggs. The ova (nits), which

Fig. 9.17: Pediculosis capitis – nits on the hair

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Fig. 9.18: Plica polonica—matting of the scalp hair

hairs behind the ears carefully for nits. The hairs may become matted from repeated scratching (plica polonica) (Fig. 9.18). • Differential diagnosis: Dandruff, here flakes come off easily from hair on manipulation. Hair casts look similar to nits but form an encompassing cylinder whereas nits are attached at an angle. Piedra is much less common and consists of clumps of fungi. • Permethrin 1% cream rinse (10 minute application) is the treatment of choice. Repeat application after one week is required to kill hatched out nits. Pyrethrins, lindane, malathion and benzyl benzoate are other agents, which can be used topically. Systemically, ivermectin, 200 µg/ kg body weight, two doses at 7 days interval may be used. Co-trimoxazole 1 tablet twice a day for 3 days, following that second course 7-10 day later. • For nit removal: After treatment, hairs are soaked with vinegar and water (50:50) and then combed with fine toothed nit comb.

• Itching is the main symptom , which is due to sensitivity to salivary antigens. • Patients harbouring body lice for long time develop hyperpigmentation of skin, develop numerous excoriations (frequently most noticeable on the side of trunk and back), secondary infection and even lymphadenopathy-vagabond’s skin, vagabond’s itch, or vagabond disease (morbus errorum). • For diagnosis: Closely examine the clothing for lice and nits along the seams. • Differential diagnosis: All pruritic dermatoses especially scabies, contact dermatitis, atopic dermatitis. • Therapy: Clothes must be disinfected. Topical antipruritics or corticosteroids are given to the patient. A course of antibiotic may be needed to take care of secondary infection.

Pediculosis Pubis • Transmission in adults occurs mostly during sexual intercourse. • The pubic or crab louse is smaller than the head or body louse, has resemblance to a crab (for prominent claws in second and third pairs of legs). • Pruritus or crawling sensation is modest in the pubic area.

Pediculosis Corporis • Infestation associated with poor personal hygiene, a disease of homeless. • The body louse feeds on body and lays its eggs on seems of clothing.

Fig. 9.19: Phthriasis pubis – adult louse clung to the hair

Infestations of insects such as mosquitoes, fleas, and bedbugs. • This condition is mainly seen in childhood. • Treatment involves use of insect repellants, topical antipruritic agents and antibacterial with or without steroids.

LARVA MIGRANS ERUPTION

Fig. 9.20: Phthriasis palpebrarum – nits attached to eyelashes

• Adult lice may be difficult to find and are usually located at the base of hairs resembling small freckles, scabs or moles (Fig. 9.19). • Other than pubic hair, body and axillary hair as well as eyelashes (phthiriasis palpebrarum) (Fig. 9.20) and beard should be examined for nits. • A classical clinical finding is the maculae cerulea—flat, indistinct, blue grey or slate colored macules in the infested area. • All the treatments suggested for pediculosis capitis are effective. Shaving the area is another option. Infestation of the eyelids is treated with twice daily applications of petrolatum for 7 to 10 days. Alternative treatments include anticholinesterase (physostigmine) eye ointments, yellow oxide of mercury, or fluorescein. The simplest technique for the treatment of eyelid lice is direct removal of the lice and nits with a fine forceps. Cryotherapy may provide a fast cure. Application of 1% gamma benzene hexachloride cream and pyrethrin ointment are other options.

• Larva migrans eruption is usually caused by filariform larvae of the dog and cat hookworms, mainly Ancylostoma braziliensis and rarely A. caninum, Uncinaria stenochepala, Bunostomum phlebotomun, or the human larvae of Necator americanus and Ancylostoma duodenale. • Adult hookworms live in the intestines of dogs and cats and their ova are deposited in the animals’ feces. Under favorable conditions of humidity and temperature, the ova hatch into infective larvae, which will penetrate human skin. Sandy, warm, moist,

PAPULAR URTICARIA • Papular urticaria occurs as episodic, symmetrically distributed, pruritic, urticarial papules that are caused by bites

Fig. 9.21: Larva migrans eruption – serpentine erythematous tract of larva migrans over the thigh of a child

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shaded areas are particularly favorable and humans acquire numerous infections. It is commonly known as creeping eruption for its distinctive feature that the lesion creep or migrate and is due to the presence of moving parasite in the skin. An irregularly linear, thin, raised burrow, 2-3 mm wide, manifests this exceedingly itchy eruption (Fig. 9.21). The larva moves a few mm to a few cm per day. The eruption is self-limited because humans are abnormal hosts. The feet and buttocks are the areas most commonly involved. Larva migrans can be accompanied by Loeffler’s eosinophilia, particularly in severe infestations. The classic clinical picture of wandering, serpentine and itchy lesion is easily recognized. Biopsy in larva migrans is of little value as the larvae have advanced beyond the clinical lesions. Differential diagnosis is granuloma annulare, migratory myiasis and larva currens. Larva currens caused by filariform larvae of Strongyloides stercoralis is characterized by wheal and flare response along the path of larvae, especially around anus and buttocks. The linear or serpiginous tracks of urticarial papules move at the rate of several cm/ hour. Demonstration of larvae of Strongyloides spp. in faeces confirms the diagnosis. The treatment of choice is the topical application of 10% thiabendazole (not available in India). Even the oral preparation of thiabendazole or two tablets of 500 mg thiabendazole crushed and formulated in 10 g petrolatum may be applied topically twice daily. Systemic use of thiabendazole, though effective, is contraindicated due to its possible poorly tolerated side effects. Ivermectin, in a single dose of 200 microgram

Fig. 9.22: Myiasis—maggots in chromomycosis lesion on the hand

per kg body weight seems best. Albendazole 400 mg daily by mouth for 3 days is safe and often effective. Flubendazole is currently at an experimental stage, appears to offer good prospects.

MYIASIS • Myiasis is the presence of fly larvae (maggots) in the tissue. • Usually they need an entry site, such as a chronic ulcer (trophic ulcer of leprosy) or wound. • Most maggots only eat necrotic debris, although some attack healthy tissue. • Clinically, myiasis is classified according to the part of the body affected-cutaneous myiasis (Fig. 9.22) (wound, furuncular), nasopharyngeal myiasis, ophthalmomyiasis, intestinal and urogenital myiasis. • Therapy-remove the maggots either after anesthetizing the area or suffocating them with turpentine oil or petrolatum.

LEISHMANIASIS Leishmaniasis is a parasitic infection caused by many species of the protozoa Leishmania, manifested clinically as four syndromes.

Infestations

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Fig. 9.23: Cutaneous leishmaniasis— noduloulcerative lesion over the forearm

• Old world type—Cutaneous leishmaniasis. • New world type—Mucocutaneous leishmaniasis. • Diffuse Cutaneous Leishmaniasis • Visceral leishmaniasis—Kala-azar. • Transmitted by infected female sand fly— Old world leishmaniasis by Phlebotomus spp. and New world leishmaniasis by Lutzomyia, Psychodopygus spp. • Life cycle: The parasite exists in two forms: a. Amastigote form in vertebrate host in cells of reticuloendothelial system or dermis. It has no flagellum. b. Promastigote form in gut of female sand fly and in culture media. It is motile with an anterior flagellum. • Oriental sore (Delhi boil, Baghdad boil) is an old world cutaneous leishmaniasis caused by Leishmania major, seen in Rajasthan and adjoining areas in India. • Unclothed parts of the body such as face, neck, and forearms are usually involved. It

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begins as papule that enlarges, ulcerates and becomes crusted nodule with surrounding induration (Fig. 9.23). Satellite lesions may occur around the main lesion. Most of the lesions heal by 6 months. Post kala-azar dermal leishmaniasis (PKDL) occurs in 20% of the patients treated for visceral leishmaniasis (Kala-azar) caused by Leishmania donovani. It is mainly confined to West Bengal, Orissa, Jharkhand and Bihar in India. The lesions appear after a year of therapy and manifest as hypopigmented macules, papules and nodules over the trunk and face. They closely resemble lepromatous leprosy, secondary syphilis and yaws. Espundia is a type of mucocutaneous leishmaniasis caused by Leishmania braziliensis. Chiclero ulcers are caused by Leishmania mexicana. Diagnosis is by demonstration of amastigotes inside macrophages from the lesion on a slit skin smear and culture in NNN media. Treatment of cutaneous leishmaniasis. A. Local therapy—Heating the sore (40-42°C), cryotherapy, B. Local infiltration of 1-2 ml of sodium stibogluconate or meglumine antimoniate, C. Systemic therapy: Antimonials—Sodium stibogluconate or meglumine antimoniate 20 mg/kg/day for 14-21 days. Pentamidine isethionate- 4 mg salt / kg – weekly doses may be used. D. Other drugs: Amphotericin B, ketoconazole, itraconazole, dapsone, rifampicin, etc.

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Papulosquamous Disorders

Papulosquamous disorders are characterized by raised, scaly papules and plaques, include psoriasis, lichen planus, pityriasis rosea, lichen nitidus, pityriasis rubra pilaris and other conditions. These are discussed below.

PSORIASIS • Psoriasis is a common chronic disfiguring, inflammatory and proliferative epidermal skin disorder mediated by T cells that affects approximately 1 to 3% of the world population. • Multifactorial inheritance most likely, a family history of psoriasis is found in 30% of patients. • The histocompatibility antigen HLA Cw6 is most strongly associated with psoriasis and the coexistence of HLA B17 or B27 portends more severe skin disease or associated psoriatic arthritis. • The pathogenesis of psoriasis remains unclear. The initial reaction is possibly an intrinsic defect of keratinocytes with increased cytokine production which leads to expansion of CD45RO + T cells with resultant production of type 1 cytokines. Subsequently, it results in epidermal proliferation, migration of neutrophils into

the epidermis, and proliferation of vessels in the papillary dermis. • The time necessary for psoriatic epidermal cell to travel from the basal cell layer to the surface and be cast off is 3 to 4 days, in marked contrast to the normal 26 to 28 days. • Precipitating factors— Stress and anxiety, alcohol and smoking, drugs (chloroquine, lithium, betablockers, ACE inhibitors, NSAID’s, etc), sudden withdrawal of systemic steroids, irritants, infections.

Classification of Psoriasis 1. Based on Morphological Types • Chronic stable plaque psoriasis (psoriasis vulgaris) (Figs 10.1 and 10.2) • Guttate psoriasis • Pustular psoriasis • Erythrodermic psoriasis • Rupioid, elephantine and ostraceous psoriasis. 2. • • • • • •

Based on Site of Involvement Scalp psoriasis Flexural (inverse) psoriasis (Fig. 10.3) Nail psoriasis Palmoplantar psoriasis Genital psoriasis Psoriatic arthritis.

Papulosquamous Disorders 3. • • • • • • • • • •

Atypical Forms of Psoriasis Linear and zonal lesions Follicular Photosensitive Seborrheic psoriasis Annular psoriasis Circinate psoriasis Nummular psoriasis Serpiginous psoriasis Geographic psoriasis Mucosal lesions— annular plaques, diffuse areas of erythema, geographic tongue; very rare • Ocular lesions— blepharitis, conjunctivitis, keratitis, xerosis, symblepharon, trichiasis, uveitis; extremely rare.

size, sharply circumscribed, dry, and usually covered with layers of silvery white, micaceous scales (Figs 10.1 and 10.2). • Grattage test involves scrapping a scaly lesion to look for type of scales. Silvery white

Clinical Features • Most lesions of psoriasis are asymptomatic. • Its typical age of onset is in the third decade, though it may develop at any time from birth onward. • Erythematous papules and plaques characterize it. The lesions are of variable

Fig. 10.2: Psoriasis vulgaris–plaque lesions over the trunk

Fig. 10.1: Psoriasis vulgaris–plaque lesions over the extensor surface of limbs and trunk

Fig. 10.3: Flexural psoriasis–psoriatic plaque involving axilla

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micaceous scales are found on doing grattage test in psoriasis. Auspitz’s sign is typical of psoriasis. It consists of three components: 1. Silvery white micaceous scales on scrapping (due to parakeratosis) 2. Shiny membrane called Bulkley’s membrane on continued scrapping (due to suprapapillary thinning of epidermis) 3. Bleeding points on removal of membrane (due to dilated capillaries in papillary dermis). Extensor surfaces of the extremities (Fig. 10.1), the scalp (Fig. 10.4) and lumbosacral region are commonly involved. Lesions of active psoriasis often appear in areas of epidermal injury-Koebner phenomenon. An acute variant, guttate or eruptive psoriasis is often seen in younger patients and is characterized by an abrupt eruption of small drop shaped lesions. It is associated with acute group A beta hemolytic streptococcal infection of pharynx in the preceding 7 to 10 days.

Fig. 10.4: Psoriasis vulgaris–lesions extending beyond hair line

• Nail involvement is common (50% of psoriasis patients). The most frequent alteration of nail plate surface is the presence of pits (Fig. 10.5). Nail matrix changes in psoriasis are pitting, longitudinal ridging, grooves, leukonychia, erythema of lunula (mottled erythema on lunula due to matrix inflammation), thickening of nails, crumbling of nail plate and trachynonychia. Nail bed changes include subungual hyperkeratosis, distal onycholysis, salmon (oily) patches, splinter hemorrhages (thin red or black longitudinal lines in distal portion of nail due to psoriatic involvement of nail bed capillaries, which are longitudinally oriented). Paronychia results from involvement of periungual skin of proximal nail fold with retention of scales between ventral nail fold and nail plate. • Psoriatic arthritis is of various types— Distal interphalangeal joint arthritis, asymmetrical oligoarthritis, polyarthritis (rheumatoid arthritis like), arthritis mutilans and predominantly axial arthritis (psoriatic spondylitis and/ or sacroiliitis). Psoriatic

Fig. 10.5: Psoriasis vulgaris–nail pitting

Papulosquamous Disorders arthritis characteristically involves the terminal interphalangeal joints (Fig. 10.6), but frequently the large joints are also affected, resembling rheumatoid arthritis. However, the rheumatoid factor is absent. • In severe cases, the disease may affect the entire skin and presents as psoriatic erythroderma. • Psoriasis rarely presents as generalized pustular psoriasis (von-Zumbusch typeacute exanthematic type (Fig. 10.7) or generalized pustular psoriasis of pregnancyImpetigo herpetiformis). Localized pustular psoriasis occurs as acrodermatitis continua of Hallopeau (localized to the distal portions of the hands and feet) (Fig. 10.8) or pustulosis palmaris et plantaris (chronic, relapsing disorder occurring on the palms, soles, or both).

Diagnosis • Psoriasis may be confused with seborrheic dermatitis, secondary syphilis, dermatophyte infections, cutaneous lupus erythematosus,

Fig. 10.6: Psoriatic arthritis—characteristically involving distal interphalangeal joint leading to swan neck deformity

eczema, lichen planus, pityriasis rosea, Bowen’s disease or lichen simplex chronicus. • Diagnosis is mostly clinical supplemented at times of doubt by histopathology of skin lesion.

Fig. 10.7: Generalized pustular psoriasisgeneralized pustular eruption in a child

Fig. 10.8: Acrodermatitis continua—nail dystrophy and finger tip involved by pustular psoriasis

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Essentials in Dermatology • Histopathology: The fully developed lesion of psoriasis shows: 1. Hyperkeratosis and parakeratosis. 2. Within parakeratotic areas of the horny layer, accumulations of neutrophils forms, which are called as Munro microabscesses. 3. Hypo or absent granular layer. 4. Regular acanthosis. 5. Spongiform pustule of Kogoj— neutrophils accumulation in Malpighian layer 6. There is regular elongation of the rete ridges with thickening in their lower portion, looking like elephant feet. 7. There is thinning of the supra papillary portion of the epidermis. 8. The dermal papillae contain enlarged and tortuous capillaries that are very close to the skin surface and impart a characteristic erythematous hue to the lesions. 9. Sparse lymphocytic infiltrate in the upper dermis.

Differential Diagnosis of Psoriasis • Seborrhoeic dermatitis— In the scalp, lesions are lighter in color, less well defined, covered with dull or branny or greasy scales, with absence of corona. • Pityriasis rosea— Papular or annular eruption usually confined to upper arms, trunk and thighs. Herald patch is followed by disseminated eruption, which has christmas tree pattern. Typically individual lesion shows collarette of scaling. Duration of disease is few weeks (6-8 weeks), and it has self limiting course. • Pityriasis rubra pilaris resembles closely the psoriasis especially in the erythrodermic phase. The follicular accentuation, focal areas of sparing (islands of normal skin), sometimes more salmon coloration of pityriasis rubra pilaris and the acquired

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palmoplantar keratoderma with yellow orange tinge help to differentiate the condition clinically; biopsy sections of pityriasis rubra pilaris may show follicular plugging, parakeratotic shoulder and perifollicular lymphohistiocytic infiltrate. Dermatophyte infection (tinea corporis)— Itchy annular erythematous plaque/s with peripheral scaling, KOH examination demonstrates dermatophytes. Discoid lupus erythematosus— Discrete erythmatous plaques on face and scalp (usually on sun-exposed areas), associated with atrophy, scaling and alopecia. Scales of discoid lesions are grayish and adherent. There is follicular plugging and carpet-tack sign. Subacute lupus erythematous— Presents with annular erythematous or psoriasiform lesions associated with systemic component, may have other components of systemic lupus erythematosus. Eczema at times develops a psoriasiform appearance especially on the legs. Hyperkeratotic eczema of palms is a common cause of misdiagnosis. Color, scratch evoked scaling and well defined margins are suggestive of psoriasis and nail changes may be diagnostic. Lichen planus— It involves flexor surface of forearm and wrists, and shins and ankles. Pruritic purple flat topped papules and plaques with scanty and tightly adherent scales. Scalp is much less frequently involved. Nails are longitudinally ridged, thickened or thinned out, with pterygium a characteristic finding. No nail pitting. Linear lichen planus may mimick linear psoriasis but the individual lesion characterstics helps in differentiating. Secondary syphilis— Asymptomatic eruption, brownish sparse scales, generalized lymphadenopathy, mucous patches, condyloma lata, positive serological test for syphilis.

Papulosquamous Disorders • Drug eruptions— Always take a drug history; many drug reactions are psoriasiform, and in some instances lead to true psoriasis in susceptible host. • Pityriasis lichenoides chronica— It can closely resemble guttate psoriasis but the lesions are less evenly scattered, have brownish red or orange brown color and are capped by an opaque soft mica like scale.

Treatment • It is important to emphasize that psoriasis is a treatable condition. The treatment pyramid for psoriasis is shown in Fig. 10.9. • Despite virtual explosion in therapeutic options, the management of psoriasis remains a challenge to clinicians.

Topical Therapies • Emollients— Such as coconut oil, vaseline, or liquid paraffin. • Coal tar (2, 5, 10% ointment)— It may be used effectively as monotherapy or in combination with other treatment modalities. Goeckerman therapy consists of black crude coal tar application all over the patient’s body. This tar is left on for 24 hours per day. UVB phototherapy is administered before the tar is applied or after it is washed off. The Goeckerman regimen remains an intensive daily therapy that is usually conducted for a period of several weeks. • Anthralin (0.1 to 10% cream or ointment)— It is moderately effective and quite safe in plaque psoriasis. The major side effect is staining of skin and clothing and occasional irritation. Ingram regimen consists of a combination of anthralin and UVB phototherapy. Short contact treatment of 30 minutes or less is likely to reduce irritation. • Topical steroids/ intralesional steroidsTopical corticosteroids are used for treatment over face and neck, flexures and genitalia, where tar or anthralin would cause irritation and cannot be used. Systemic steroids

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generally not recommended due to the wellknown risk of rebound and pustular conversion. Vitamin D analogues are both naturally occurring – calcitriol (1α, 25-dihydroxyvitamin D 3 ) and synthetic analoguescalcipotriol, tacalcitol, maxacalcitol. Vitamin D molecule is dispensed as ointment, cream or solution and has risk of producing hypercalcemia in less than 1% of cases. Tazarotene (0.1 to 0.05% gel)— It is a modified vitamin A molecule formulated as a topical agent. It is recommended for use in patients with total body surface involvement of 20% or less. Topical methotrexate gel-used for palmoplantar psoriasis with limited efficacy. Tacrolimus (0.03, 0.1%) effective for facial plaques and inverse psoriasis.

Medications Used in Phototherapy • Concurrent use of topical or oral medications, psoralen (5 methoxy psoralen, 8 methoxy psoralen, trimethyl psoralen) along with UVA or UVB phototherapy is done. • Psoralen along with UVA from sunlight (PUVASOL). • Narrow band UVB. • Methotrexate and PUVA combination (Me-PUVA). • Retinoids and PUVA combination (RePUVA). • Excimer LASER (308 nm). Systemic Medications for Psoriasis • Methotrexate (0.4 to 0.6 mg per kg body weight)— Used for severe cases of psoriasis, taken orally just once a week. It is an effective and well tolerated drug in appropriately selected patients who are receiving folate supplementation, and who are adequately monitored for potential toxicities. • Cyclosporine (3-5 mg per kg body weight). Cyclosporine has dose-related nephrotoxicity and hypertension that impede its use as a

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long-term agent for most patients. Nevertheless, cyclosporine is an effective drug for rapid clearing in most patients. Cyclosporine, when used in the appropriate patient at the appropriate dose (usually 2.5 to 5.5 mg/kg daily), is an excellent “bridging agent” that can be used safely for periods of 2–12 months. Etretinate and Acitretin (0.5-1 mg per kg body weight)— They are the treatment of choice for generalized pustular psoriasis. Acitretin is less effective when used as monotherapy for plaque psoriasis. Hydroxyurea (maximum up to 500 mg three times a day). Sulfasalazine (3-4 gm/day). Mycophenolate mofetil ( 1-2 gm/day, can increase maximum up to 4 gm/day). Oral tacrolimus ( 0.05- 0.15 mg/kg body weight per day). Fumaric acid esters 30 mg per day up to 240 mg three times a day. Many of these medications are used in combination and rotated periodically. HIV associated psoriasis may respond to zidovudine based HAART regimen.

Biologic Agents Biologics are agents that selectively block the immunologic steps in the pathogenesis of psoriasis. Alefacept, efalizumab, etanercept, and infliximab are currently approved for the treatment of adults with moderate to severe plaque psoriasis, and phase 3 trials for adalimumab are ongoing (Table 10.1). • All biologics approved to date for the treatment of psoriasis are recommended for patients who are candidates for systemic or photo-therapy. Table 10.1: Biologic agents and their mechanism of action

Strategy

Biologic agents

Reduction of the number of pathogenic T cells

Alefacept, denileukin diftitox

Inhibition of T-cell activation and migration

Efalizumab, daclizumab, siplizumab, CTLA4Ig, galiximab,

Modulation of the immune system

Ilodecakin, oprelvekin

Blockage of the activity of inflammatory cytokines

Etanercept, infliximab, adalimumab, ABX-IL8

Fig. 10.9: Treatment pyramid of psoriasis

Papulosquamous Disorders • Efalizumab is favorable in patients with high risk of latent tuberculosis or evidence of demyelinating disease. • Infliximab is advantageous where rapid disease control is required (e.g. unstable erythroderma). • Etanercept is the biologic of choice in stable psoriasis where a TNF-α-blocking strategy is appropriate. • Some biologics are also approved for treatment of psoriatic arthritis; thus, patients with psoriatic arthritis may benefit from a biologic for both the articular and dermatologic manifestations.

• Cutaneous lesions occur in about half of affected patients. The cutaneous eruption has limpet like scales (Figs 10.10 and 10.11). Lesions have a predilection for the glans penis (balanitis circinata) (Fig. 10.12), the palms and soles (keratoderma blennorrhagica) and the subungual areas. • HLA B 27 is present in about 80% of cases • Most cases of Reiter’s disease are probably caused by infection with micro-organisms that infect urogenital or gastrointestinal systems such as Chlamydia trachomatis,

Course and Prognosis • The course of psoriasis is prolonged but unpredictable. REITER’S DISEASE • Reiter’s disease predominantly affects young men and consists of the triad of urethritis, arthritis, and conjunctivitis. As few patients present with classic triad, the American College of Rheumatology recognizes criteria for limited manifestations of this syndrome including peripheral arthritis of more than one month duration in association with urethritis, cervicitis or bilateral conjunctivitis.

Fig. 10.10: Reiter’s disease–typical limpet like scales

Fig. 10.11: Reiter’s disease–typical lesions over legs

Fig. 10.12: Reiter’s disease-circinate balanitis

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Essentials in Dermatology Ureaplasma urealyticum, Shigella, Salmonella, etc. • Differential diagnosis includes rheumatoid arthritis, ankylosing spondylitis, gout, psoriatic arthritis, gonococcal arthritis, acute rheumatic fever, etc. • Mucocutaneous lesions are generally self limited and clear with topical steroids. Refractory lesions are managed like psoriasis. Joint disease may require NSAIDS, methotrexate or biologics (infliximab).

LICHEN PLANUS • Lichen planus (Greek leichen, “tree moss”; Latin planus, “flat”) is a subacute or a chronic dermatosis that may involve skin, mucous membranes, hair follicles and nails. • The cause of lichen planus is unknown, but several etiologies have been proposed. It is likely that both endogenous-genetic and exogenous-environmental components such as drugs or infection may interact to elicit the disease. • The prevalence of chronic liver diseases, including primary biliary cirrhosis, alcoholic cirrhosis, hepatitis B, and especially hepatitis C, is increased. • HLA-B8 is more common in patients with oral lichen planus as the sole manifestation,

Fig. 10.13: Lichen planus–violaceous, flat-topped papules

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and HLA-Bw 35 is more strongly associated with cutaneous lichen planus. At least two-thirds of cases occur between the ages of 30 and 60 years. Cutaneous eruption is characterized by small, flat topped, shiny, polygonal, violaceous papules that may coalesce into plaques (Fig. 10.13) The papules often show a network of white lines known as Wickham’s striae. Koebner phenomenon commonly seen (Fig. 10.14). Itching is usually pronounced. The four P’s – purple, polygonal, pruritic, papule- is the abbreviation used to recall the constellation of symptoms and skin findings that characterize lichen planus. The disease has a predilection for the flexor surfaces of the forearms (Fig. 10.15), legs (Fig. 10.16), trunk (Fig. 10.17), and the genitalia including the glans penis (Figs 10.18 to 10.20).

Fig. 10.14: Lichen planus–wrist involved, Koebner phenomenon also seen

Papulosquamous Disorders • The oral lesions of lichen planus are frequently found, either as sole manifestation of the disease or associated with cutaneous involvement. Most often consist of a lacy, reticular network of coalescent papules over the buccal (Fig. 10.21) or glossal mucosa. Besides this, it forms plaque like, atrophic, papular, erosive and bullous lesions. • The nails are involved in about 10% of cases and show roughening, longitudinal ridging, thinning and dystrophy. Pterygium

Fig. 10.17: Lichen planus–trunk involved by typical violaceous papular lesions

Fig. 10.15: Lichen planus–flexor aspect of arm involved

Fig. 10.18: Lichen planus–an annular lesion over the glans penis

Fig. 10.16: Lichen planus–hypertrophic violaceous papules and plaques over legs

Fig. 10.19: Lichen planus–male genitalia involved by lichen planus

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Fig. 10.20: Lichen planus–female genitalia involved by lichen planus

Fig. 10.21: Lichen planus–lacy white network over the buccal mucosa

Fig. 10.22: Lichen planus–pterygium unguium formation in some finger nails

Fig. 10.23: Lichen planus–transeversely aligned lichen planus along Blaschko’s lines

formation is a frequent finding (Fig. 10.22). • Common variants of lichen planus (LP) are classified on the basis of: A. Configuration (annular, linear, zosteriform/along Blaschko’s lines (Fig. 10.23), B. Morphology of lesions (hypertrophic, atrophic, vesicobullous, erosive, ulcerative, follicular [planopilaris], actinic (Fig. 10.24), LP pigmentosus, perforating, guttate), C. Site of involvement (palms and soles, mucous membranes, nails, scalp),

D. Special forms (drug induced, overlap syndrome of lichen planus/lupus erythematosus, LP pemphigoides).

Diagnosis • The appearance of the typical papule of lichen planus is usually sufficient to make the correct diagnosis. • Histopathology: Microscopic features, similar to the gross morphology, are diagnostic. The two major pathologic findings in lichen planus are basal epidermal keratinocyte damage and lichenoid-interface lympho-

Papulosquamous Disorders

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• • Fig. 10.24: Lichen planus actinicus–typical hypopigmented halo around pigmented violaceous lesions over the face

cytic reaction. The histologic features are summarized here: 1. Hyperkeratosis 2. Wedge shaped hypergranuloses which is responsible for the Wickham’s striae seen clinically 3. Irregular acanthosis 4. Damage to basal cell layer 5. The rete ridges are pointed at their lower end and the papillae between rete ridges are often dome shaped thus resembling the old styled bridges on rivers having tapering down pillars and domes in between. This pattern is also called as “saw-tooth” pattern. 6. A band-like dermal lymphocytic infiltrate closely hugs the epidermis. 7. Max-Joseph spaces are seen in some cases as a sub-epidermal clear zone. Melanin incontinence and vascular inflammatory reaction probably give purple colour to LP lesions.

Differential Diagnosis • Classic lesions: Lichenoid drug eruption (large scaly lesions in sun-exposed areas, devoid of Wickham striae, residual pigmentation common), lichen nitidus

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(asymptomatic pinhead sized shiny papular lesions, rarely involves mucous membranes), secondary syphilis, pityriasis lichenoides et varioliformis acuta, early pityriasis rubra pilaris. Hyperkeratotic lesions: Lichen simplex chronicus, prurigo nodularis, lichen amyloidosis, warts. Linear lesions: Lichen striatus, linear epidermal naevus, linear psoriasis. Annular lesions: Granuloma annulare, secondary syphilis, psoriasis Lichen planopilaris: For early lesionskeratosis pilaris, other follicular keratoses, Darier’s disease, early pityriasis rubra pilaris. For advanced lesions-discoid lupus erythematosus, and other forms of scarring alopecia. Wide-spread erosive oral lesions must be differentiated from those of candidiasis (curdy white deposits which on removal leaves an erythematous base. KOH scrapping shows budding yeasts, pseudohyphae), aphthous ulcers (well circumscribed shallow ulcers with a necrotic gray centre and an erythematous halo. It usually heals in around six weeks) pemphigus (ill defined irregular buccal or palatal non healing painful erosions. Other mucosal sites may also be involved. Nikolsky’s sign positive), cicatricial pemphigoid (vesicles, persistent extensive erosions, desquamative gingivitis with eroded bleeding gums, adhesions between buccal mucosa and alveolar process and around uvula and tonsillar fossae, involvement of other mucosal sites including conjunctiva, genital mucosa, larynx and esophagus, and decreased mouth opening due to fibrosis), carcinoma (usually malignant ulcers are painless unless secondarily infected. On palpation induration of base may be present), and erythema multiforme (usually involves lips,

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Essentials in Dermatology palate and gingival. On lips, target lesions may be identified. Vesicles, erosions and crusting are present over oral mucosa. Associated skin lesions- target lesions may be seen over acral extensor sun-exposed areas).

Treatment • Topical therapy: Topical glucocorticoids are typically used for mucosal and limited cutaneous disease. • Intralesional therapy: Intralesional triamcinolone acetonide (5 to 10 mg/mL) is effective in treating oral and cutaneous lichen planus. • Systemic therapy: 1. Systemic glucocorticoids are often useful and effective in doses greater than 20 mg/day (e.g. 30 to 60 mg prednisolone) for 4 to 6 weeks with subsequent taper over 4 to 6 weeks. 2. PUVA photochemotherapy is usually successful in generalized cutaneous lichen planus. 3. The systemic retinoids demonstrate antiinflammatory activity and have been used in the treatment of lichen planus. 4. Cyclosporine (500 mg) rinses in oral lichen and systemic cyclosporine in recalcitrant lichen planus has been used successfully. 5. Other agents used in lichen planus are dapsone, griseofulvin, cyclophosphamide, methotrexate, phenytoin and extracorporeal photochemotherapy. In mucosal lichen planus, topical corticosteroids, tetracycline, betamethasone mouthwashes 0.5 mg 3-4 times daily, topical tretinoin gel, cyclosporine mouth rinses, tacrolimus, and pimecrolimus have been used. Maintenance of good oral hygiene and replacement of amalgam or gold dental restorations with composite material is frequently of considerable benefit. Erosive oral lichen planus may respond to oral dapsone.

Course Lichen planus is a benign disease with spontaneous remissions and exacerbations. Apart from hypertrophic lichen planus, most of LP lesions tend to involute after several months to a year. LICHEN NITIDUS • Lichen nitidus is a chronic dermatitis usually asymptomatic which begins commonly in childhood or early adulthood • It is characterized by minute, round, flat or dome shaped, shiny, flesh colored papules 2 to 3 mm in diameter that may occur in groups • Predominantly, the arms, trunk (Fig. 10.25) or penis (Fig. 10.26)are involved • Koebner phenomenon may be observed (Fig. 10.27) • The histology of a typical papule is characteristic. A circumscribed epithelioid cell granuloma is situated immediately below the epidermis. The rete ridges at the margin of the infiltrate are elongated and tend to encircle it “claw clutching a ball appearance”. • Differential diagnosis: 1. Keratoses pilaris (horny follicular papules on extensor surfaces),

Fig. 10.25: Lichen nitidus–flat, shiny, flesh colored papules on the trunk

Papulosquamous Disorders 2. Lichen scrofulosorum (grouped follicular papules in small patches on trunk), 3. Lichen planus, 4. Sarcoidosis, 5. Disseminated granuloma annulare, 6. Eruptive xanthomas,

7. Plane warts (more variable in size, have verrucous surface and present with fewer lesions with few anatomic sites involved) • As the disease is often asymptomatic and eventually self-limiting, no treatment is required in most cases • Topical steroids may be recommended if treatment is demanded.

PITYRIASIS ROSEA

Fig. 10.26: Lichen nitidus–flat, shiny, flesh colored papules on the glans penis

Fig. 10.27: Lichen nitidus- over the arm showing Koebner phenomenon

• Pityriasis rosea is a self limited dermatitis lasting from 4 to 7 weeks. • The etiology is unknown, though a viral origin has been suggested. • Predominantly occurs in adolescents and young adults. • May be asymptomatic or pruritic (50% of cases). • It frequently starts with herald patch (mother patch, plaque primitive, primary medallion, primary plaque) (most commonly on the trunk) followed by a disseminated eruption (the trunk and proximal extremities) within several days to 2 weeks (Fig. 10.28). Sometimes, herald patch may be missing, or present as double or multiple lesions often close together.

Fig. 10.28 Pityriasis rosea–herald patch with a few daughter lesions showing “collarette of scaling”

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Essentials in Dermatology • Round to oval salmon colored patches following the lines of cleavage (Christmas tree like pattern) and showing peripheral attached thin cigarette paper like scales (“collarette of scaling”) (Fig. 10.28). When individual lesion is stretched along the long axis, the scales tend to fold across the lines of stretch, so called “hanging curtain sign”. • Variants of pityriasis rosea are vesicular, inverse (Fig. 10.29), cervicocephalic, pityriasis rosea gigantea (pityriasis circinata et marginata of Vidal), pityriasis rosea urticata, purpuric pityriasis rosea, pityriasis rosea perstans, pustular pityriasis rosea, and eczematous pityriasis rosea.

white micaceous scales), parapsoriasis, pityriasis lichenoides chronica, lichen planus, and, most importantly, secondary syphilis (maculopapular lesions, no herald patch, genital and oral mucosal involvement).

Treatment • Most patients require no treatment. • Topical corticosteroids or short course of oral corticosteroid may be required in severe cases. • Oral erythromycin may be helpful. • Itching alleviated with antipruritic lotions or antihistamines. PITYRIASIS RUBRA PILARIS (PRP)

Diagnosis • Usually easily diagnosed by its morphology and distribution. Differential Diagnosis • Pityriasis rosea must be differentiated from tinea corporis, tinea versicolor (well defined hypopigmented coalescing macules with branny scales), drug eruptions (acute onset without herald patch, pruritic protracted rash and a tendency for lesions to become lichenoid), psoriasis (papules and plaques with silvery

• Pityriasis rubra pilaris is an erythematous squamous disorder characterized by seborrheic dermatitis like rash which progresses cephalo-caudally, follicular plugging and perifollicular erythema that coalesces to form orange red scaly plaques (Fig. 10.30) that frequently contain islands of normal appearing skin (Fig. 10.31), proximal phalanges showing typical follicular plugging and palms and soles keratotic sandal (palmoplantar keratoderma) (Fig. 10.32).

Fig. 10.29: Inverse pityriasis rosea – lesions over the face

Fig. 10.30: Pityriasis rubra pilaris – follicular papular lesions coalescing to form plaques over the trunk

Papulosquamous Disorders • • • •

Fig. 10.31: Pityriasis rubra piliaris–islands of normal skin in a patient having erythroderma

Fig. 10.32: Pityriasis rubra pilaris–palmoplantar keratoderma (keratotic sandal)

• It may progresses to erythroderma. • Both familial and acquired forms of the disorder have been described.

Types of PRP • Type I—adult onset classical, most common type. • Type II—adult onset atypical. • Type III—juvenile onset, classical.

Type IV—juvenile onset, circumscribed. Type V— juvenile onset, atypical. Type VI—HIV associated. Histopathology reveals hyperkeratosis and follicular plugging with shoulder of parakeratosis. Parakeratosis may alternate both vertically and horizontally producing a checkerboard pattern. • Differential diagnosis: Closely resembles psoriasis but prominent facial involvement or follicular lesions speak against it. Early scalp involvement is often mistaken for atopic dermatitis or seborrhoeic dermatitis. Early diffuse lesions are confused with lichen planus and pityriasis lichenoides et varioliformis acuta. Circumscribed pityriasis rubra pilaris mimics phrynoderma or keratosis pilaris. • Treatment: Topical therapy with keratolytic agents, vitamin D analogues and systemic therapy with vitamin A, acitretin, isotretinoin (systemic retinoid), methotrexate and retinoid plus psoralen and ultraviolet A (RePUVA) has been tried with variable efficacy. Antiretroviral therapy is of value in pityriasis rubra pilaris like eruption of HIV infection. • The inherited form of the disorder is persistent throughout life while the acquired disease usually shows remissions and exacerbations.

ERYTHRODERMA (EXFOLIATIVE DERMATITIS) • Erythroderma is a condition which is characterized by erythema, infiltration and scaling involving more than 90% of the body surface area or near universal involvement of the body (Fig. 10.33). • Erythroderma can be caused by various dermatological disorders: eczema, psoriasis, drugs, lymphoma, leukaemia, pemphigus foliaceus, ichthyosiform erythroderma, pityriasis rubra pilaris, lichen planus,

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Essentials in Dermatology • In erythroderma where the etiology is unknown, called as idiopathic erythroderma (10% of cases). • Chronic erythroderma of unknown origin with prolonged course in the elderly is called as ‘red man syndrome’. • Sézary syndrome manifest with erythroderma, generalized lymphadenopathy and atypical cells in peripheral smear (more than 10%). • It can be a manifestation of internal malignancy.

Fig. 10.33: Erythroderma – near universal involvement by erythema, scaling and infiltration

dermatomyositis, dermatophytosis and crusted scabies. • The drugs causing erythroderma are phenytoin, carbamazepine, cimetidine, lithium, gold, chloroquine, isoniazid, mercury, thiazide, quinidine and pyrazolone derivatives.

Complications • Erythroderma leads to hemodynamic and metabolic disturbances such as high out put cardiac failure, hypothermia, dehydration and hypoalbuminemia. • Temperature regulation is affected and patient behaves like a poikilothermic animal. • Death may occur due to cardiac failure, pneumonia and septicemia. Management It includes maintenance of the homeostasis and treatment of the primary disease.

Eczema

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Eczema

The word eczema is derived from the Greek word “ekzein” meaning “to boil out” or “to effervesce”. Eczema is an inflammatory skin reaction characterized histologically by spongiosis with varying degrees of acanthosis, and a superficial perivascular lympho-histiocytic infiltrate. The clinical features of eczema may include itching, redness, scaling and clustered papulo-vesicles. The condition may be induced by a wide range of external and internal factors acting singly or in combination. The terms ‘dermatitis’ and ‘eczema’ are nowadays generally regarded as synonymous, although some authors still use the term ‘dermatitis’ to include all types of cutaneous inflammation, so that all eczema is dermatitis, but not all dermatitis is eczema.

CLASSIFICATION OF ECZEMA Exogenous Eczema • Irritant dermatitis • Allergic contact dermatitis • Photoallergic contact dermatitis • Eczematous polymorphic light eruption • Infective eczema • Dermatophytide • Post-traumatic eczema.

Endogenous Eczema • Atopic dermatitis • Seborrheic dermatitis • Asteatotic eczema • Discoid eczema • Pompholyx • Pityriasis alba • Stasis dermatitis • Hand eczema • Lichen simplex chronicus • Prurigo nodularis • Lichen striatus • Juvenile plantar dermatosis • Metabolic eczema or eczemas associated with systemic disease • Eczematous drug eruptions. It must be remembered that, endogenous and exogenous factors may co-exist. For example, hand eczema, which is an endogenous eczema, is often aggravated by exogenous factors. Some of the important endogenous (Atopic dermatitis, seborrheic dermatitis, nummular eczema, pompholyx, pityriasis alba, stasis dermatitis, asteatotic eczema, lichen simplex chronicus, prurigo nodularis, lichen striatus) and exogenous eczema (Contact dermatitis, infective eczema/ dermatitis, polymorphous light eruption) are discussed as follows.

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ATOPIC DERMATITIS • Atopic dermatitis (AD) or eczema is a common chronic or relapsing dermatitis characterized by severe pruritus, occurring primarily in infants and children. • The age of onset is between 2 and 6 months in the majority of cases, but it may start at any age, even before the age of 2 months in some cases. • The disease arises as a result of a complex interplay between various genetic, immunological and environmental factors. • The environmental factors include (a) physical factors like sweating, climate, warm surroundings, detergents and soap, synthetic or woollen fabrics, cigarette smoke, (b) psychological factors, (c) food items (including tomato, orange and citrus fruits juices, meat, fish) (d) allergens such as house dust mite, animal hair, pollen, plants and others such as Staphylococcus aureus and release of exotoxins (superantigens) and saliva in small children. • Majority of cases are associated with a sensitization to environmental allergens and increased serum IgE (extrinsic AD), but about 10-30% of all cases lack any link to the classical atopic diathesis and are labelled as intrinsic AD. • There is no laboratory gold standard for the diagnosis of AD. A detailed history and a characteristic clinical picture would establish the diagnosis. Hanifin and Rajka have laid down certain major and minor criteria for making a diagnosis of AD.

Must have Three or More Major Findings • Pruritus • Typical morphology and distribution (Flexural lichenification or linearity in adults; Facial and extensor involvement in infants and children).

• Chronic or chronically relapsing dermatitis • Personal or family history of atopic dermatitis (e.g. asthma, allergic rhinitis, atopic dermatitis).

Plus Three or More Minor Findings • Xerosis • Ichthyosis • Palmar hyperlinearity • Keratosis pilaris • Immediate (type 1) skin test reactivity • Elevated serum IgE level • Early age of onset • Tendency towards extraneous infections (especially with Staphylococcus aureus and herpes simplex) or impaired cell mediated immunity • Propensity towards nonspecific dermatitis of the hand or foot. • Nipple eczema • Cheilitis • Recurrent conjunctivitis • Dennie -Morgan infraorbital fold • Keratoconus • Anterior subcapsular cataracts • Orbital darkening • Pityriasis alba • Facial pallor or facial erythema • Anterior neck folds • Itch when sweating • Intolerance to wool and lipid solvents • Food intolerance • White dermographism or delayed blanch. Course of atopic dermatitis may be divided in three phases: 1. Infantile phase 2. Childhood phase 3. Adult phase The distribution of lesions varies with age: Face (Fig. 11.1)and scalp involvement is common in infants as well as the extensor surfaces of the extremities and the trunk. In the childhood phase of AD 18-24 months onwards, eczema is

Eczema

Fig. 11.1: Atopic dermatitis—face

Fig. 11.2

Fig. 11.3

Figs 11.2 and 11.3: Atopic dermatitis–discoid eczematous lesions also appearing on flexor aspect of limbs in a child

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Essentials in Dermatology observed on the flexural surfaces, including the neck, antecubital or popliteal fossae, wrists and ankles (Figs 11.2 and 11.3). There is an adult phase, which occurs in adolescents and adults, where lichenification of the flexures and the hands commonly occurs. Some important signs: Thinning of lateral eyebrows, Hertoghe’s sign is sometimes present. Hyperkeratosis and hyperpigmentation producing a “dirty neck” appearance is also frequent in atopic individuals. Atopic individuals often exhibit perioral, perinasal and periorbital pallor “headlight sign”. Differential diagnosis: The diagnosis of atopic dermatitis (AD) is rarely aided by investigations. In the individual patient, one must consider a number of other conditions. Scabies should always be excluded, and can cause confusion when superimposed on pre-existing AD. In the first few months of life, the differentiation of infantile seborrhoeic dermatitis from atopic dermatitis can be difficult, although with time the distinction becomes apparent. The most useful distinguishing feature between atopic dermatitis and seborrheic dermatitis is the increased number of lesions on the forearms and shins in the former and axillae in the latter. The development of the lesions solely in the diaper area favors a diagnosis of infantile seborrheic dermatitis. Absent to mild pruritus is considered a significant feature of infantile seborrheic dermatitis. Immunodeficiency states should also be considered in infants in whom the disease is unusually severe, when there are recurrent systemic or ear infections and if there is failure to thrive, malabsorption or petechiae. Then appropriate investigations should be performed, for example, immunoglobulin levels and subclasses, IgE levels, white cell count, platelets, complement levels, and function, and T, B, and phagocyte numbers and functions. If clinically appropriate, one may also consider testing for

HTLV-I and human immunodeficiency virus (HIV). Treatment: No disease is more complicated to treat than atopic dermatitis. It is absolutely essential to counsel and educate the patient and their parents. Avoidance of exacerbating factors like wool clothes, house dust mites, detergents, dietary or aero-allergens, stress, etc. is advised wherever implicated. The treatment is aimed at suppressing the symptoms and controlling or preventing complications. Besides emollients for routine skin care, topical corticosteroids (TC) are the mainstay of treatment for AD to control acute exacerbations and can be used safely if certain precautions are taken. Topical calcineurin inhibitors (TCIs: Tacrolimus 0.03% and 0.1% and Pimecrolimus 1%) are recommended in patients of AD who are unresponsive to or intolerant to other conventional therapies, should be applied over the affected areas twice daily. Tacrolimus 0.03% and 0.1% formulations are recommended for the use in adults, whereas only 0.03% formulation is recommended for use in children aged 2-15 years, often first line for face, intertriginous areas and genitalia, useful in early flare, continue treatment till disease clears (approximately 1 month), and is useful for maintenance therapy. Systemic corticosteroids have a limited role in tiding over occasional flares of severe AD. Sedative antihistamines such as hydroxyzine and promethazine are preferred to non-sedative ones to control pruritus. Avoidance of provoking factors is paramount to achieve control. • Other treatment modalities include phototherapy and photochemotherapy, cyclosporin, evening primrose oil, azathioprine, Chinese herbal medicines, interferons, thymopentin, human interferon gamma and plasmapheresis. • Algorithmic approach to management depending upon severity of AD.

Eczema

1.

Mild AD

Bland emollients and parents/patient counseling Mild to moderate TCs, followed by TCI or TCI as first line of therapy Sedative anti-histamines

2.

Moderate AD

Bland emollients and parents/patient counseling Initial control with TCs and at the earliest shift to TCI’s Anti-histamines Narrow band UVB Systemic corticosteroids for short period

3.

Severe AD

Bland emollients and parents/patient counseling Anti-histamines Systemic antibiotics Oral corticosteroids/cyclosporine/azathioprine

• Course and prognosis— Atopic dermatitis follows a highly variable course with exacerbations and remissions. About 95% of children with AD remit around puberty, but relapses m ay occur and the disease may persist well into adulthood.

SEBORRHEIC DERMATITIS (SD) • Seborrheic dermatitis is a common, endogenous eczema that is usually easily recognized. • It affects infants and adults and is often associated with increased sebum production (seborrhea) of the scalp and the sebaceous follicle–rich areas of the face and trunk. • Various genetic factors, hormonal factors and increased colonization of Malassezia may play a role in the causation and perpetuation. • Seborrheic dermatitis has two age peaks, one in infancy within the first 3 months of life and the second around the second to the third decade of life. Men are affected more often than women in all age groups.

Classification of Seborrhoeic Dermatitis Infantile • Scalp (Cradle cap) • Trunk (including flexures and napkin areas) • Leiner’s disease.

Adult • Scalp: — Dandruff — Inflammatory • Face (may include blepharitis and conjunctivitis) • Trunk: — Petaloid — Pityriasiform — Flexural — Eczematous plaques — Follicular. • Generalized (may be erythroderma) • In infants, the scalp (the frontal and parietal scalp regions are covered with an oilylooking, thick, often fissured crust -crusta lactea (milk crust, or cradle cap) (Fig. 11.4), face and diaper areas are often involved. Leiner’s disease is due to complement C5 deficiency, presents as erythroderma. • Clinically, adult patients develop erythema and greasy scale on the scalp (with often pruritus), paranasal areas, eyebrows, nasolabial folds, central chest and intertriginous folds (seborrheic areas of the body). Rarely generalized lesions may occur. Dandruff is usually the earliest manifestation of seborrheic dermatitis.

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Fig. 11.4: Seborrheic dermatitis-cradle cap in an infant

Fig. 11.5: Seborrheic dermatitis in an adult–greasy scaling with erythema involving eyebrows, nasolabial folds and beard area in a HIV case

• ‘Corona seborrheica’, when SD on the scalp extends beyond the frontal hairline onto the forehead. • Sebopsoriasis: Early stage of scalp psoriasis may closely resemble seborrheic dermatitis with similar clinical and histological features. Some believe that seborrheic dermatitis may be a precursor of scalp psoriasis. • SD occur more commonly in variety of medical disorders like parkinsonism, myocardial ischemia, malabsorption, epilepsy, obesity and alcoholic pancreatitis. • SD can be a cutaneous marker of early HIV infection (Fig. 11.5). • Patients with HIV infection often have severe recalcitrant disease. • The disease is usually protracted over weeks to months. The prognosis is good. • Differential diagnosis: 1. HIV must be ruled out as patients with HIV tend to have extensive/severe SD.

2. Scalp psoriasis: The lesions are well defined, palpably thickened, brighter pink in colour with silvery scales. 3. Infective dermatitis complicating pediculosis may mimic SD. 4. Truncal SD should be differentiated from pityriaisis rosea, tinea versicolor. 5. Flexural SD should be differentiated from tinea, candidiasis, erythrasma. 6. Follicular SD should be differentiated from Darier’s disease. 7. SD-like lesions can occur in acrodermatitis enteropathica. 8. Drugs producing SD-like rash: Methyl dopa, chlorpromazine, cimetidine. • Treatment: In general, therapy is directed towards loosening and removal of scales (daily shampoo containing selenium sulfide, zinc pyrithione, ketoconazole, cetavalon, salicylic acid, coal tar; topical corticosteroids; topical antifungals like imidazoles) and

Eczema crusts, inhibition of yeast colonization, control of secondary infection, and reduction of erythema and itching. For unresponsive cases, narrow band UVB, oral ketoconazole, itraconazole or terbinafine may be used. Other treatment modalities include topical metronidazole (1%) gel, topical lithium succinate, vitamin D 3 analogues, and oral isotretinoin. • Patients should be informed about the chronic nature of the disease and understand that therapy works by controlling the disease rather than by curing it.

NUMMULAR ECZEMA (NE) (DISCOID ECZEMA) • The word nummular means (Latin nummulus) –‘coin like’. • Etiology of this is unknown. • It mainly affects men aged 55-65 years. • The eruption is characterized by pruritic, coin shaped, eczematous lesions (Fig. 11.6) • The lesion tends to develop on the extensor surfaces of the extremities and trunk.

• Differential diagnosis: NE may simulate tinea corporis (where scaling of the edge is more conspicuous, scrapings shows presence of mycelia). Exogenous dermatitis and irritant dermatitis occasionally presents with discoid response. In psoriasis, the lesions are dry, the scaling is more prominent and the irritation is milder. • NE has a chronic course with frequent relapses. • Treatment: open wet compresses, topical steroids and antibiotics for secondary infection.

POMPHOLYX (DYSHIDROSIS) • Pompholyx is characterized by itchy deepseated vesiculation on the palms and sides of the fingers. Lesions appear ‘sago-like’. • It may involve the soles of the feet. • It occurs bilaterally symmetrically, has relapsing course. • Differential diagnosis: 1. Id eruptions: Id eruptions are pompholyxlike eruptions due to distant focus of infections (e.g. kerion or bullous tinea pedis) 2. Pustular psoriasis of palms and soles: Sterile pustules, absence of clear vesicles, and characteristic residual brown marks as the lesions subside 3. Pemphigoid lesions occurring on the palms 4. Bullous tinea pedis • Treatment: open wet compresses, topical steroids and antibiotics for secondary infection.

PITYRIASIS ALBA

Fig. 11.6: Nummular eczema—coin shaped eczematous lesions over the leg

• Pityriasis alba is a common disorder in children that is characterized by an asymptomatic, hypopigmented, slightly elevated, fine, scaling plaque with indistinct borders.

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Essentials in Dermatology • It usually disappears by adulthood. • The condition commonly affects the face. • Differential diagnosis: 1. Indeterminate leprosy: Lesion is usually solitary to a few, hypopigmented macule with ill-defined margins and equivocal sensory loss. 2. Tinea versicolor: Lesions are well-defined hypopigmented macules with branny scales. KOH examination shows ‘spaghetti and meatball’ appearance. 3. Vitiligo-early lesions may mimic but lack scaling. 4. Mycosis fungoides although relatively rare may present with lesions clinically resembling pityrasis alba. • Treatment: Emollients, mild topical steroid or topical pimecrolimus or tacrolimus application may suffice.

STASIS DERMATITIS • Stasis dermatitis occurs as a result of venous stasis on the lower portions of the legs. • The dermatitis may be acute, subacute or chronic. • It differs from other forms of dermatitis, firstly by showing brownish black pigmentation and secondly, by resulting in some instances in ulceration and atrophic scarring. • The surrounding skin may show changes due to venous stasis–hyperpigmentation, induration of skin and lipodermatosclerosis in late stage. • Differential diagnosis: 1. Allergic contact dermatitis usually caused by topical medications. Patch testing is helpful. 2. Infected ulcer with infective eczematoid dermatitis around the ulcer responds to appropriate antibiotic therapy. 3. Discoid eczema is common on lower legs usually on the anterior or anterolateral aspect.

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4. Asteatotic eczema commonly affects the legs of elderly. 5. Dermatophyte infection may present as diffuse erythema and scaling and can be difficult to recognize, particularly if it has been treated with topical steroids. 6. Psoriasis may present as a single irritable plaque on the leg but is usually more scaly and clearly marginated Treatment: The underlying venous hypertension should be controlled. Well fitted stockings can be helpful if worn regularly. The legs should be elevated when patient is recumbent. Topical steroids may be used to relieve irritation.

ASTEATOTIC ECZEMA (ECZEMA CRAQUELE, WINTER ECZEMA, DERMATITIS SICCA) • It is an eczema associated with a decrease in skin surface lipids. • The eczema occurs after excessive drying, especially during the winter months and among the elderly and those with atopic dermatitis or ichthyosis vulgaris. • The skin of the limbs and trunk is erythematous, dry and itchy and shows a fine crazy-paving pattern of fissuring. • Differential diagnosis: Atopic dermatitis, various forms of ichthyosis especially acquired ichthyosis. • Treatment: Central heating should be humidified where possible. Avoidance of frequent bath, use of synthetic detergent instead of soap, regular lubrication of the skin especially after bathing helps. Weak topical steroids are often prescribed.

LICHEN SIMPLEX CHRONICUS (NEURODERMATITIS) • Lichen simplex chronicus is characterized by lichenified plaque lesion or lesions due to

Eczema repeated rubbing or scratching as a habit or due to “stress”. • Lichenification of the skin follows chronic scratching and/or rubbing. This may occur without a predisposing dermatosis, or may follow any pruriginous dermatosis. The term lichen simplex is used when there is no predisposing dermatosis. • It is characterized histologically by acanthosis and hyperkeratosis and clinically by thickened appearance of the skin, with accentuation of skin markings so that the affected skin surface resembles tree bark.

Fig. 11.7: Lichen simplex chronicus—thickening, and pigmentation of ankle

Fig. 11.9: Lichen simplex chronicus-involving female external genitalia

• The areas most commonly affected are those that are conveniently reached. • These areas are ankles (Fig. 11.7) and wrists, nape of neck (Fig. 11.8), genitalia (scrotum or mons pubis) (Fig. 11.9), etc. • It is common in Indian subcontinent amongst adults (30-50 years). • Differential diagnosis: The morphological diagnosis of lichenification is not usually difficult-lichen planus, lichen amyloidosis, and psoriasis have to be excluded and typical lesions sought in other sites. • Treatment: Patient should be given some assistance in reducing their tension. Sedation is often needed and sedative antihistaminics may be helpful. In most cases, a steroid cream is the treatment of choice. To prevent the scratching and to improve the outcome of the treatment, steroid may be applied under polythene occlusion.

PRURIGO NODULARIS (PN, HYDE’S PRURIGO)

Fig. 11.8: Lichen simplex chronicus— involving nape of neck

• Prurigo is a Latin word for itching. • PN is an intensely pruritic disorder in which persistent rubbing and scratching in particular area leads to formation of distinctive hemispherical nodules with raised warty surface (Fig. 11.10).

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Fig. 11.11: Lichen striatus—linearly arranged flat topped papular lesions over the chest of a child

Fig. 11.10: Prurigo nodularis—raised itchy nodular lesions over the legs and dorsa of feet

• Disease occur in 20-60 years of age, both sexes are equally affected. • The cause is unknown. The initial trigger for itching in PN may include local trauma, insect bite reactions and atopic eczema, etc. • Differential diagnosis: 1. Hypertrophic lichen planus: Usually violaceous, may be associated with typical lichen planus lesions elsewhere. 2. Pemphigoid nodularis may present as nodular prurigo for sometime before typical urticated plaques and blisters supervene. 3. Allergic contact dermatitis may result in papulonodular eruptions. 4. Systemic causes of pruritus that can give rise to lesions resembling nodular prurigo include renal failure, liver disease, lymphoma, and HIV infection. • Treatment: Oral antihistamines, emollients, topical steroids with salicylic acid and

intralesional steroids, cryotherapy, and systemic agents such as thalidomide, cyclosporine and azathioprine.

LICHEN STRIATUS • It is an acquired self-limited inflammatory linear skin disorder • Exact etiology is unknown • Children aged 5 to 15 years are commonly affected • The most characteristic lesion is a linear band of hypopigmented lichenoid papules that follow Blaschko’s lines (Fig. 11.11) • The lesions commonly occur on the arm or leg • Course of the lesion may extend for 2 weeks to 4 months. • Differential diagnosis: Epidermal naevi (persist indefinitely), linear lichen planus or psoriasis (easily differentiated clinically, even in the absence of typical lesions in other sites which should always be sought for) • Treatment: Usually none is necessary, topical steroids, topical tacrolimus and intralesional steroids in persistent cases.

Eczema

HAND ECZEMA • Hand eczema is not a single diagnostic entity. It is rather a morphological presentation of various types of eczemas largely confined to the hands and can have a multitude of factors responsible for causing it, singly or in combination. Causes of hand eczema are broadly grouped into two groups as shown below:

Exogenous 1. Contact irritants: Chemicals (e.g. soaps, detergents, solvents) Physical (e.g. friction, minor trauma, cold dry air) 2. Contact allergens: Delayed hypersensitivity (e.g. chromium, rubber) Immediate hypersentivity (e.g. seafood) 3. Ingested allergens (e.g. drugs, nickel, chromium) 4. Infection (e.g. bacterial infections of hand wounds) 5. Secondary dissemination (e.g. dermatophytide reaction to tinea pedis). Endogenous 1. Idiopathic (e.g. Discoid, hyperkeratotic palmar eczema) 2. Immunological or metabolic defects (e.g. atopics) 3. Psychosomatic: Stress aggravates, but may not be causative 4. Dyshidrosis: Increased sweating aggravates, but may not be causative. Morphological types of Hand Eczema 1. Pompholyx 2. Recurrent focal palmar peeling 3. Hyperkeratotic palmar eczema 4. Ring eczema 5. ‘Wear and tear’ dermatitis

6. Fingertip eczema 7. Apron eczema 8. Discoid eczema 9. Chronic acral dermatitis 10. Gut eczema. • Differential diagnosis: The diagnosis of hand eczema is usually self evident but distinction from psoriasis is very difficult. In most cases of psoriasis on hands, however, the silvery nature of the scales, involvement of knuckles, sharply demarcated scalloped edges to the erythema along the borders of the hands and fingers, and the relative absence of pruritus are helpful pointers. Family history of psoriasis and the presence of nail pits in the absence of nail fold lesions are also suggestive. Tinea can also be missed especially when it is extensive and irritable or secondarily infected. Unilateral scaling of palm should always suggest tinea manuum. • Treatment of hand eczema: Avoidance of irritants, frequent application of emollients, and sparing use of topical steroids.

JUVENILE PLANTAR DERMATOSIS (FOREFOOT ECZEMA) • Occurs mainly in children aged 3-14 years of age. • The presenting features are redness and pain on the plantar surface of the forefoot, which assumes a glazed and cracked appearance. • The condition is most severe on the ball of the foot and toe pads, and tends to spare the non-weight-bearing instep. • The symmetry of the lesions is a striking feature. • Differential diagnosis: The toe clefts are normal, and this helps to distinguish the condition from tinea pedis. Patch testing to exclude foot wear allergy may be done. • Treatment: Most cases will clear spontaneously during childhood or

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CONTACT DERMATITIS Contact dermatitis is an eczematous dermatitis caused by exposure to substances in the environment. Common types of contact dermatitis are discussed here.

Irritant Contact Dermatitis (ICD) • ICD is a non-immunological eczematous reaction which occurs without previous sensitization in most exposed individuals. • Most common type of contact dermatitis. • Common irritants include alkalis (soaps, detergents), dye and ammonia containing compounds. • The clinical features vary from mild xerosis to erythema/chapping or even severe ulceration depending on the concentration of the irritant, the skin area exposed, mode of contact and the substance itself. • The reaction remains localized and does not spread to become generalized and it does not cause systemic symptoms. • Acute irritant dermatitis is characterized by vesicles and bullae (e.g. cement dermatitis, savlon induced reaction). • Chronic irritant dermatitis manifests as hyperkeratosis, fissuring and scaling (e.g. house wife dermatitis). • Healing usually occurs within 2 weeks of removal of noxious stimulus. • In cases of chronic subcritical level of irritation, some develop tolerance or hardening. • Differential diagnosis: Same as for allergic contact dermatitis • Treatment: avoidance of irritants, use of bland barrier creams, protective gloves and mild topical steroids.

Allergic Contact Dermatitis (ACD) • ACD results when an allergen comes in contact with previously sensitized skin. • It is a delayed hypersensitivity reaction, consisting of sensitization phase and when rechallenged-elicitation phase. • Occurs in individual of all ages, especially elderly. • Sensitization remains lifelong. • The allergens are extremely varied and may be nonprotein in nature. • Common causes of ACD include plants, nickel (Fig. 11.12), chromate, para phenylene diamine (hair-dye) (Figs 11.13 and 11.14),

Fig. 11.12: Contact dermatitis—dermatitis over abdomen due to trouser metallic hook

Fig. 11.13: Contact dermatitis—erythema and edema due to acute dermatitis caused by hair dye

Eczema

Fig. 11.14: Contact dermatitis—lichenoid dermatitis over the forehead due to hair dye

Fig. 11.16: Common agents involved in contact dermatitis of the face

Fig. 11.15: Contact dermatitis—dermatitis due to rubber chappal

rubber compounds (Fig. 11.15), fragrances and preservatives in compounds. • The eczematous reactions develops at the sites of skin contact with the allergen (Fig. 11.16) but occasionally spreads outside these limits and cause systemic symptoms. • The patch test is diagnostic and helps to identify allergens involved. • Patch test consists of application of substances suspected to be the cause of the contact dermatitis to the intact uninflammed skin, in nonirritating concentration.

• Most common plant allergen in India is Parthenium hysterophorus. • Most common metal causing ACD is nickel • Differential diagnosis: Main differential diagnostic consideration is irritant contact dermatitis. Others are erysipelas (rapidly spreading, non-pruritic, well defined erythematous area, and patient is sick), atopic dermatitis, nummular eczema, tinea (KOH examination), seborrhoeic dermatitis, polymorphous light eruption, and angioedema • Treatment: The most important step is avoidance of allergens. Acute dermatitis of any sort is best treated with moist compresses and high potency corticosteroid creams. In severe cases, a short burst of systemic corticosteroids tapered over 7-10 days is needed. More chronic cases can be treated with lower potency corticosteroids in an ointment base. Oral cyclosporine is indicated for therapy resistant chronic disease.

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DIFFERENCES BETWEEN IRRITANT CONTACT AND ALLERGIC CONTACT DERMATITIS Irritant contact dermatitis

Allergic contact dermatitis

*People at risk *Mechanism of response *Prior exposure required *Nature of substance

Everyone Nonimmunologic No Organic solvents, soap

*Concentration of substance required *Symptoms *Lesions *Involvement of non-exposed sites *Type of inflammatory cells *Patch test

Usually high Severe, stinging or burning sensation Large tense bullae with necrosis No Neutrophils Not useful

Genetically predisposed Delayed hypersensitivity Yes Low molecular weight hapten (metal, formalin) May be low Pruritus Papules or papulovesicles Yes Eosinophils and lymphocytes Diagnostic

INFECTIVE DERMATITIS (INFECTIOUS ECZEMATOID DERMATITIS, MICROBIAL ECZEMA) • Infective eczema is caused by microorganisms or their products, clears when organisms are eradicated. • It is seen predominantly around discharging wounds or ulcers or moist skin lesions of other types. • It presents as an area of advancing erythema, sometimes with microvesicles (Fig. 11.17). • Treatment: Factors predisposing to infection should be sought and when possible eliminated. Wet compresses, topical antibiotic in combination with steroid or systemic antibiotic.

POLYMORPHIC LIGHT ERUPTION (PMLE) • PMLE is the most common photodermatoses. • The disease may begin at any age and the symptoms are severe in spring and summer season. • It is an idiopathic eruption caused by UV exposure; appears in hours to days with varied morphology (papular variant most

Fig. 11.17: Infective dermatitis—oozing dermatitic lesions behind ear and trunk

common, papulovesicular, eczematous, erythematous, plaque like). Clinically, it presents as non scarring, erythematous, itchy papules, plaques or vesicles on exposed skin that usually heal without scarring. • The amount of light exposure needed to elicit an eruption varies greatly from one patient to another.

Eczema • Light sensitivity decreases with repeated sun exposure, this phenomenon is referred to as hardening. • Differential diagnosis: Lupus erythematosus, photosensitive drug eruption, prurigo nodularis, and photoallergic contact dermatitis need to be differentiated.

• Treatment: Photoprotection by clothing and sunscreens, phototherapy, and topical steroids. In severe resistant cases, consider the use of azathioprine 50-100 mg daily for 3 months. Use antioxidants, one week before exposure may help in prevention.

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12

Vesiculobullous Disorders

Vesiculobullous disorders cause significant morbidity and mortality in dermatology. While a number of disorders of varied etiology can present with vesicles or bullae, two distinct groups of disorders are the genetic blistering diseases (epidermolysis bullosa) and the acquired autoimmune blistering disorders (pemphigus, bullous pemphigoid, dermatitis herpetiformis, chronic bullous dermatosis of childhood, epidermolysis bullosa acquisita). Vesiculobullous disorders are diseases where the primary lesion is a vesicle or bulla. It occurs due to pathology in the epidermis or dermoepidermal junction or dermis. In this chapter we are not dealing with secondary causes of vesiculation like to burns, suction blisters, ischemia leading to blisters (vasculitis, diabetic bulla), drug eruptions like bullous fixed drug eruption, insect bite reaction, infections (varicella, herpes simplex, herpes zoster), dermatitis, miliaria, etc. This chapter would discuss primary vesiculobullous disorders. In epidermal autoimmune vesiculobullous disoders, the mechanism behind blister formation is primarily acantholysis in most cases. Decreased stability of basement membrane is responsible for a variety of subepidermal vesiculobullous disoders which could be either inherited or of acquired autoimmune origin.

CLASSIFICATION OF VESICULOBULLOUS DISORDERS 1. Inherited/genetic blistering disorders: a. Epidermolysis bullosa simplex b. Junctional epidermolysis bullosa c. Dystrophic epidermolysis bullosa. 2. Acquired autoimmune blistering disorders: a. Intraepidermal immunobullous diseases 1. Pemphigus vulgaris and its variant pemphigus vegetans. 2. Pemphigus foliaceous and its variants i. Endemic pemphigus foliaceus (Fogo selvagem; wild fire). ii. Pemphigus erythematosus (SenearUsher syndrome) iii.Pemphigus herpetiformis. 3. Drug induced pemphigus. 4.. IgA pemphigus i. Intraepidermal neutrophilic type ii. Subcorneal pustular dermatosis type. 5. Paraneoplastic pemphigus. 6. Subcorneal pustular dermatosis (Sneddon –Wilkinson disease). 3. Subepidermal immunobullous diseases a. Bullous pemphigoid and its variants b. Mucous membrane pemphigoid (cicatricial pemphigoid)

Vesiculobullous Disorders c. Pemphigoid gestationis (Herpes gestationis) d. Linear IgA disease/Chronic bullous dermatosis of childhood e. Dermatitis herpetiformis f. Epidermolysis bullosa acquisita g. Bullous systemic lupus erythematosus. The following discussion deals with these two groups of disorders with special focus on the more common entities.

EPIDERMOLYSIS BULLOSA • Epidermolysis bullosa (EB) comprises a group of genetically determined skin disorders characterized by blistering of the skin (Fig. 12.1) and mucosae at birth or soon afterwards, following mild mechanical trauma (due to increased fragility of skin). Thus an alternative term for these disorders could be the ‘mechanobullous’ disorders. • There are three main types of EB: – EB simplex (intraepidermal split due to disruption of basal keratinocytes) – Junctional EB (split through the basement membrane zone) – Dystrophic EB (split in the subepidermal level).

Fig. 12.1: Epidermolysis bullosa—baby showing multiple erosions

• EB simplex is the commonest and mildest form of EB of autosomal dominant inheritance. It is characterized by onset of blistering over trauma prone sites at birth or infancy. Lesions heal without scarring. Mucosae, nails and hair are essentially uninvolved. • Junctional EB are autosomal recessive disorders and are broadly classified into two main types, the lethal and non-lethal forms. They present at birth or soon after with severe fragility of the skin leading to extensive blistering and denudation. Oropharyngeal mucosae may be severely involved. Teeth may be malformed and prematurely lost and nails may be shed. This is the most fatal type of EB. • Dystrophic EB is characterized by skin fragility, scarring with milia (Fig. 12.2), nail changes (Fig. 12.3) and have either autosomal recessive or dominant inheritance. The more severe autosomal recessive form is characterized by:

Fig. 12.2: Epidermolysis bullosa dystrophica–knee showing hemorrhagic bullae with scarring, milia and pigmentation

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Essentials in Dermatology • Gene therapy appears as a realistic goal in the future.

PEMPHIGUS

Fig. 12.3: Epidermoloysis bullosa dystrophica– albopapuloid lesions over the dorsa of feet and some of the toenails completely lost

– Onset at birth or early infancy – Blistering of skin mainly over trauma prone sites – Oral blisters and scarring leading to ankyloglossia and microstomia – Esophageal lesions causing painful dysphagia and later esophageal strictures. – Perianal blistering, erosions and scarring causing stenosis and fecal retention. – Ocular complications—symblepharon, corneal erosions and opacity – Repeated blistering and progressive scarring—contractures and deformities (e.g. ‘Mitten hands’). • Diagnostic techniques include skin biopsy, electron microscopy to ascertain the level of split and structures involved, antigen mapping and immunohistochemistry. No autoantibodies are demonstrated in the sera. Prenatal DNA testing can be advised to couples at risk of having affected children. • No specific treatment is available for EB and thus the mainstay of treatment is based on avoidance of provoking factors. Management of the neonate includes maintaining adequate nutrition and hydration and prevention of sepsis. Other aspects include care of the oral cavity, teeth, eyes and management of contractures and deformities.

• Pemphigus is derived from the Greek ‘pemphix’ meaning blister or bubble and is characterized by intraepidermal blistering at various levels in the epidermis. • The key pathogenic process in this group of disorders is disruption of the intercellular cementing substance due to an autoantibody attack on the cellular adhesion proteins (desmogleins) leading to acantholysis. • The pemphigus group of disorders includes two major types (and their variants) and several other minor types. The major types are: – Pemphigus vulgaris (variant – Pemphigus vegetans): level of split-suprabasal. – Pemphigus foliaceus (variant – Pemphigus erythematosus): level of split – subcorneal. • The other minor types of pemphigus include paraneoplastic pemphigus, drug induced pemphigus, IgA pemphigus and neonatal pemphigus.

Pemphigus Vulgaris • Most common form of pemphigus, accounting for up to 80% of pemphigus cases. Occurs at any age, most commonly between fourth- sixth decades. In India, it occurs at younger age. • It is due to IgG antibodies directed against epidermal cell adhesion molecules (desmoglein 3)- disruption of intercellular cementing substance—loss of adhesion between epidermal cells (acantholysis) intraepidermal blistering. Clinical Features • Almost all patients have mucosal lesions, 50–70% present with painful oral erosions. Lesions may be limited to oral cavity for months to one year (Fig. 12.4).

Vesiculobullous Disorders • Skin – flaccid bullae on normal or erythematous skin, with a predilection for scalp, face (Fig. 12.5), trunk (Figs 12.6 and 12.7), axillae and groins and pressure sites. Bullae rupture producing painful erosions that show no tendency to heal spontaneously. • Pruritus is absent or negligible. • Nikolsky’s sign and Bulla spread sign (Asboe-Hansen sign) are positive. (Other disorders with positive Nikolsky’s sign are

staphylococcal scalded skin syndrome, toxic epidermal necrolysis, etc.). • Other mucosae involved are conjunctiva, pharynx, larynx, oesophagus, urethra, vulva and cervix.

Fig. 12.4: Pemphigus vulgaris—painful erosions involving tongue and lips

Fig. 12.5: Pemphigus vulgaris—extending erosions without tendency to heal over the face

Fig. 12.6: Pemphigus vulgaris—involving chest

Fig. 12.7: Pemphigus vulgaris—involving back

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Essentials in Dermatology • Prognosis is poor without treatment but with systemic steroids mortality has been reduced to 5–15 %. • Pemphigus may be associated with other autoimmune diseases such as thymoma, myasthenia gravis and malignancies like lymphomas and bronchogenic carcinoma.

Diagnosis • Tzanck smear from the floor of the blister shows acantholytic cells. Acantholytic cell is a large, rounded epidermal cell with a large nucleus, perinuclear halo and peripheral condensation of cytoplasm (Fig. 12.8). • Histopathological examination of a blister shows a supra-basal cleft in the epidermis. The basal keratinocytes remain attached to the basement membrane but are separated from each other and stand like a ‘row of tombstones’. • Immunofluorescence studies are the gold standard in diagnosis of the autoimmune blistering disorders. In pemphigus vulgaris, direct immunofluorescence done on the lesional skin shows deposition of intercellular IgG throughout the epidermis in a ‘fish-net’ pattern (Fig. 12.9). Indirect immunofluorescence done to determine levels of pathogenic antibodies in the sera of the

Fig. 12.8: Tzanck smear showing large rounded epidermal cells with large nuclei, perinuclear halo and peripheral condensed cytoplasm (Acantholytic cell)

Fig. 12.9: Direct immunofluorescence showing fish net pattern

patients shows circulating intercellular IgG antibodies in 80–90% of the cases. Levels of these antibodies correlate with disease activity.

Pemphigus Vegetans It is a clinical variant of pemphigus vulgaris characterized by vegetating lesions primarily in the flexures (Figs 12.10 and 12.11). Initial lesions are bullae or pustules, which rupture and progress to form vegetating plaques. Pemphigus Foliaceous • This disorder, characterized by blistering at a higher level in the epidermis is less common than pemphigus vulgaris and accounts for only 15–20 % of pemphigus cases. • It is caused by IgG antibodies directed against intercellular adhesion molecules (desmoglein 1) found predominantly in the upper epidermis—disruption of intercellular cementing substance of upper epidermal cellssubcorneal blister formation. • Clinically, pemphigus foliaceous is less severe than pemphigus vulgaris and is characterized by crusted, moist, scaly lesions in a seborrheic distribution (Fig. 12.12) involving scalp, face, chest and upper back. Blistering may not be obvious due to the superficial level of the split (very transient nature of blisters).

Vesiculobullous Disorders

Fig. 12.10: Pemphigus vegetans—vegetating moist lesions occurring in the axilla

Fig. 12.12: Pemphigus foliaceous—moist scaly lesions in seborrheic areas of the face

Fig. 12.11: Pemphigus vegetans—vegetating moist lesions in the retroauricular area

• Oral lesions are uncommon. • Nikolsky’s sign is invariably positive (Fig. 12.13).

Fig. 12.13: Nikolsky’s sign – tangential pressure with finger tip producing moist erosion due to peeling of skin

Diagnosis • Tzanck smear from fresh erosion shows acantholytic cells. • Histology shows a subcorneal cleft with acantholysis.

• Immunofluorescence findings are usually indistinguishable from pemphigus vulgaris. Prognosis of this disorder is better than pemphigus vulgaris. This benign disorder responds well to treatment.

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Pemphigus Erythematosus It is a variant of pemphigus foliaceous characterized by immunological features of both pemphigus and lupus erythematosus (LE), that is, intercellular IgG and C3 in the epidermis (as in pemphigus) and in the basement membrane zone (as in LE) and antinuclear antibodies (as in LE). Clinically, erythematous, scaly rash over the nose and cheeks simulate LE while lesions on the trunk are similar to those in pemphigus foliaceous. Other Variants of Pemphigus • Endemic pemphigus foliaceous (Fogo Selvagem) is a variant of pemphigus foliaceous, endemic to certain parts of South America and is postulated to be precipitated by bites of the black fly (Simuliidae). The burnt appearance and burning sensation gave the disease its name, fogo selvagem, meaning “wild fire”. • Drug induced pemphigus (penicillamine, captopril, pyritinol, penicillin, rifampicin)— clinically commonly present as pemphigus foliaceous. • Paraneoplastic pemphigus—a polymorphous blistering eruption with mucocutaneous ulcerations having an underlying neoplasm. • Pemphigus herpetiformis—superficial vesicles and inflammatory papules occur in herpetiform distribution. • IgA pemphigus—has bound and circulating IgA autoantibodies against intraepidermal cell surface antigens and clinically may resemble subcorneal pustular dermatosis. • Juvenile pemphigus— pemphigus occurring before 20 years of age • Neonatal pemphigus— due to transplacental transfer of maternal anti-intercellular cement substance antibodies to the fetus. Blisters resolve in 2 weeks.

Differential Diagnosis When skin is involved, other autoimmune vesiculobullous disorders need to be differentiated from pemphigus. On rare occasions, bullous impetigo, dyskeratotic acantholytic disorders (Darier’s disease, Hailey Hailey disease, Grover’s disease) can cause a problem. When only the oral mucosa is involved, the following should be considered-aphthous ulcerations, oral erosive lichen planus, herpetic gingivostomatitis, erosive candidiasis, and erythema multiforme. When both skin and oral mucosa are involved, it closely resembles erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, bullous systemic lupus erythematosus, and generalized bullous fixed drug eruption. Treatment of Pemphigus • The mainstay of therapy in the pemphigus group of disorders is with systemic steroids, which can be given as conventional therapy (oral prednisolone in the dose of 1 mg per kg body weight) or as pulse therapy. An upcoming mode of therapy is the dexamethasone cyclophosphamide pulse regimen consisting of 100 mg of IV dexamethasone in 5% dextrose infusion on 3 consecutive days of each month combined with IV cyclophosphamide 500 mg bolus dose on day 1 of the pulse and oral cyclophosphamide 50 mg daily on other days. This therapy reduces the conventional side effects of steroids. • The other modalities of therapy include adjuvant therapy with dapsone, azathioprine, cyclosporine, methotrexate, gold salts, mycophenolate mofetil, intravenous immunoglobulin therapy and plasmapheresis and are essentially to reduce the side effects of steroids or to control the severe form of pemphigus.

Vesiculobullous Disorders

BULLOUS PEMPHIGOID (BP) • Autoimmune subepidermal blistering disorder of the elderly, with onset usually after 60 years of age. • Basic pathogenic process is due to IgG antibodies against components of the basement membrane zone (BMZ – structure which binds epidermis to the underlying dermis and mesenchyme)— loss of structural integrity of the BMZ due to resultant inflammation separation of the intact epidermis from underlying dermissubepidermal cleft formation.

Clinical Features • Preceded by pruritus with or without urticarial wheals lasting usually for 1–3 weeks. • Tense bullae on normal or erythematous skin predominantly over flexural aspects of the limbs (Fig. 12.14), lower abdomen (Fig. 12.15), groins and axillae. Facial skin and scalp relatively spared. – Lesions rupture to leave erosions that heal spontaneously with postinflammatory hyperpigmentation. – Nikolsky’s sign usually negative; Bulla spread sign +/– Mucosal lesions rare and less severe than in pemphigus vulgaris and almost never the presenting feature. • Bullous pemphigoid may be associated with an underlying malignancy (gastric carcinoma commonly) and may be associated with diabetes mellitus, rheumatoid arthritis and psoriasis. Diagnosis • Tzanck smear will show numerous eosinophils with few neutrophils but no acantholytic cell.

Fig. 12.14: Bullous pemphigoid—itchy urticarial lesions over the thigh developing into tense bullae

Fig. 12.15: Bullous pemphigoid—involving lower back

• Histopathological examination reveals subepidermal cleft with intact epidermis forming the roof of the blister. • Direct immunofluorescence of perilesional skin shows linear IgG (45–90%) and C3 (80–100 %) deposition in the basement membrane zone. Indirect immunofluorescence studies done on the patient’s sera show circulating IgG autoantibodies in most cases but unlike in pemphigus, their titers do not correlate with disease activity.

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Differential Diagnosis Bullous pemphigoid can be easily differentiated from most other blistering disorders such as linear IgA disease, chronic bullous disease of childhood, dermatitis herpetiformis, erythema multiforme and pemphigus by histology and immunofluorescence. Most difficult diseases to differentiate from bullous pemphigoid are epidermolysis bullosa acquisita and cicatricial pemphigoid. • Prognosis of bullous pemphigoid is better than pemphigus and it runs a chronic selflimiting course. It may be fatal in the active stage in the elderly or debilitated patients.

Fig. 12.16: Cicatricial pemphigoid— tense bulla over the tongue

Treatment • The mainstay of treatment is a topical or systemic steroid depending on the severity of the disease. Pulse dexamethasone cyclophosphamide, methyl prednisolone or cyclophosphamide pulse may be used. Other modalities include cyclophosphamide, azathioprine, dapsone, tetracycline with nicotinamide, erythromycin, leflunomide, sulphapyridine, methotrexate, mycophenolate mofetil, intravenous immunoglobulin therapy and plasmapheresis.

Fig. 12.17: Cicatricial pemphigoid—face showing symblepharon

Clinical Variants of Bullous Pemphigoid Include • Cicatricial pemphigoid is a rare blistering disorder of the mucosa and skin that results in permanent scarring of the affected area. Mucosal lesions predominate and involve in decreasing order the oropharynx (Fig. 12.16), nasopharynx, conjunctiva, larynx, genitalia and esophagus. Sequelae include oropharyngeal adhesions, esophageal strictures, stridor, introital shrinkage, symblepharon (Fig. 12.17) and ‘statue eye’. Unlike bullous pemphigoid, this disorder is not self-limiting and has a chronic debilitating course.

• Herpes gestationis is a non-viral autoimmune blistering disease of young women that occurs in pregnancy (21–28 weeks of gestation) or within 1st week postnatally. Clinically, the disease starts as severe pruritus with urticarial wheals and plaques followed by blistering predominantly in the periumbilical area, lower abdomen and thighs. Mucosal involvement is rare and lesions improve postpartum. Recurrence may occur in subsequent pregnancies, premenstrually or with oral contraceptive pills (OCPs). Direct immunofluorescence shows linear C3 deposits at the BMZ with IgG in some cases.

Vesiculobullous Disorders

Characteristic

Bullous pemphigoid

Pemphigus vulgaris

Age Pruritus Blister Sites Erosion Nikolsky’s sign Oral lesions

> 60 years ++ Tense Flexures, groins, axillae, abdomen Spontaneously heal Negative 40 % less severe, almost never a presenting feature Benign, self limiting

Middle age Not present Flaccid Face, scalp, trunk, pressure points Extend peripherally Positive 80–90 % severe commonly the presenting symptom Poor without treatment

Prognosis

DERMATITIS HERPETIFORMIS (DH) • DH is defined as an intensely pruritic, chronic, recurrent, papulovesicular disease with an underlying gluten-sensitive enteropathy which may be asymptomatic.

Clinical Features • Onset at any age, usually between 20–55 years of age. • Males outnumber females. • Pruritus is the first and predominant symptom followed by a symmetrical eruption of erythematous papules and papulovesicles, which are so rapidly excoriated that intact vesicles are difficult to demonstrate (Fig. 12.18). • Sites – extensor aspects of limbs (elbows and knees), buttocks, natal cleft, shoulders, upper back (Fig. 12.19), face and scalp. Grouping of lesions accounts for it being described as herpetiformis (not associated with herpes virus). • Oral lesions are common but asymptomatic. • Provocation of lesions occurs with iodides orally or in iodide patch testing. • Histological examination best done on lesions that have not blistered or ruptured and reveals neutrophilic microabscesses at the tips of dermal papillae.

Fig. 12.18: Dermatitis herpetiformis—extremely itchy tense grouped vesicular lesions over the shoulder area

Fig. 12.19: Dermatitis herpetiformis—bilateral symmetrical distribution of itchy eroded lesions over the extensor aspect of limb and trunk

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Essentials in Dermatology • Direct immunofluorescence is the most reliable diagnostic criterion and should be performed on clinically normal skin (preferably of the buttocks). It reveals granular IgA deposits in dermal papillae. • Indirect immunofluorescence is negative for anti-BMZ or dermal autoantibodies but antithyroid and antigliadin antibodies may be seen.

chronic bullous disease/dermatosis of childhood (CBDC), with onset in childhood and linear IgA disease which presents in adults. There is lot of overlap in the clinical presentation of the two entities but they differ in their age at presentation and few clinical signs. In linear IgA disease, periorificial and annular lesions are not as common as in CBDC. Hemorrhagic bullae may be present.

Differential Diagnosis Dermatitis herpetiformis can be confused with numerous conditions because of its pleomorphic manifestations and occasional lack of diagnostic lesions. Scabies, bullous pemphigoid before the development of blisters, and the prurigo group of disoders are the main issues. It also needs to be differentiated from chronic exudative eczema, papular urticaria, neurotic excoriations, and transient acantholytic dermatoses. A high index of suspicion is very helpful, even in the absence of primary lesions. Dermatitis herpetiformis can be diagnosed based on the typical in vivo bound granular IgA deposits in normal appearing skin.

Chronic Bullous Disease/dermatosis of Childhood (CBDC, Linear IgA disease of Childhood) • CBDC is defined as a chronic acquired autoimmune subepidermal blistering disease of children characterized by IgA BMZ antibodies. • Onset is usually at around 5 years of age (toddlers and preschool children). • Urticarial plaques with blistering at the edges – ‘string of pearls’ appearance and localization of lesions around orifices (perioral, perigenital) (Figs 12.20 and 12.21).

Treatment • Dapsone 100–200 mg/day (up to 400 mg /day) is the drug of choice. It is amazingly effective; hours to days after the first dose, the pruritus disappears and no new lesions erupt after 1-2 days of treatment. • Strict adherence to a gluten-free diet for prolonged periods (e.g. 6 to 12 months) may control the disease in some patients, obviating or reducing the requirement for drug therapy. LINEAR IgA DISEASE It is a chronic acquired subepidermal blistering disorder of children and adults, with skin and mucous membrane involvement and characterized by linear deposition of IgA at basement membrane zone. It consists of two main entities-

Fig. 12.20: Chronic bullous dermatosis of childhood— clustering of tense bullae around the mouth

Vesiculobullous Disorders combined with low dose steroids in refractory cases.

Fig. 12.21: Chronic bullous dermatosis of childhood– lower limbs showing “cluster of jewels” appearance at many sites

• Spontaneous remission usually occurs with age. • Direct immunofluorescence shows linear IgA at BMZ.

Differential Diagnosis In young infant, bullous impetigo may resemble the initial lesions, but its response to antibiotics differentiates it. Epidermolysis bullosa often present at birth and family history further differentiates it. Bullous papular urticaria rarely affects the face or genital region and it is usually of short duration. Childhood bullous pemphigoid may give us similar clinical picture but the deposition of IgG and C3 at the BMZ is diagnostic. Treatment is the same. Dermatitis herpetiformis only occurs in small children (usually occurs between 20 and 55 years of age) who are heterozygous for predisposing HLA genes. Treatment • Dapsone is usually effective (response usually occurs within 24-48 hours), and may be

Disorder

Site of split

Pathogenic antibody

P. vulgaris P. foliaceous/ erythematosus Paraneoplastic pemphigus BP / HG / CP EBA Dermatitis herpetiformis CBDC

Suprabasal Subcorneal

IgG IgG

Suprabasal

IgG

Subepidermal Subepidermal Subepidermal

IgG and C3 IgG IgA

Subepidermal

IgA

(Note: Epidermolysis bullosa are a group of genetic disorders with structural defects but NO autoantibodies.)

EPIDERMOLYSIS BULLOSA ACQUISITA (EBA) • It is defined as a chronic, acquired autoimmune blistering disorder characterized either by trauma-induced subepidermal blistering or with a clinical picture indistinguishable from bullous pemphigoid. • IgG class of autoantibodies directed against collagen VII causes it. Collagen VII is the major component of the anchoring fibrils found in the subepidermal zone; (differentiate from hereditary epidermolysis bullosa dystrophica in which there is a collagen VII structural defect leading to reduced or absent collagen VII in the anchoring fibrils). The five clinical presentations of EBA are: 1. Classical presentation– Noninflammatory tense bullae over trauma prone areas which heal with scarring and milia formation. Hemorrhagic bulla may be seen. It is a mechanobullous disease marked by skin fragility. 2. Bullous pemphigoid–Like presentation– widespread inflammatory vesiculobullous eruption over trunk, flexures and extremities.

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Essentials in Dermatology Tense bullae are present over inflamed or urticarial skin. Hemorrhagic bulla may be seen. Large areas of erythema and urticaria without blistering can be seen. Patient complains of pruritus and does not show prominent skin fragility, scarring or milia formation. The clinical picture is more like a bullous pemphigoid than a mechanobullous disorder. 3. Cicatricial pemphigoid-like presentation– is marked by widespread mucosal involvement. Clinical appearance is similar to cicatricial pemphigoid. Erosions and scars over mucosal surfaces of mouth, upper esophagus, conjunctiva, anus or vagina are present with or without similar lesions over glabrous skin. 4. Brunsting-Perry pemphigoid-like presentation– is a chronic recurrent vesiculobullous eruption localized to head and neck. It is characterized by bullae healing with scarring and has minimal to no mucosal involvement. 5. IgA bullous dermatosis-like eruption– is characterized by tense veskcles arranged in an annular pattern and mucous membrane involvement. It is also differentiated from other EBA types by its DIF findings of linear

•

•

•

•

deposition of IgA at basement membrane zone. Histology shows subepidermal cleft with neutrophilic infiltrate in the BP type while sparse inflammatory infiltrate in the mechanobullous type. Direct immunofluorescence (DIF) on perilesional skin shows thick polyclonal band of deposition of IgG and C3 and sometimes IgA and IgM in the BMZ. DIF on salt split skin shows deposits of IgG and C3 on dermal side whereas in bullous pemphigoid in 85% cases deposits are present on epidermal side and in 15% cases, it may be seen on both epidermal and dermal sides. EBA is a very difficult disease to treat. Steroids in combination with dapsone or adjuvant immunosuppressives (azathioprine, methotrexate, cyclophosphamide, cyclosporine, high doses of colchicine) are the usual line of therapy. Photopheresis and intravenous immunoglobulin have been used. The mechanobullous type is resistant to most modalities of treatment. Supportive therapy is warranted in all patients with EBA. This includes instructions in open wound care and strategies in avoiding trauma.

Cutaneous Tuberculosis and Atypical Mycobacterial Infections

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Cutaneous Tuberculosis and Atypical Mycobacterial Infections

Tuberculosis of the skin constitutes about 10% of all extra-pulmonary tuberculosis which in turn constitutes only a fraction of all cases of tuberculosis.

CLASSIFICATION OF CUTANEOUS TUBERCULOSIS (TB) Types

Mode of infection

Bacilli

Immunity

Tuberculin

Primary TB * TB chancre *Miliary TB

Inoculation Hematogenous

+++ ++

-

-

Secondary TB *Lupus vulgaris *TBVC *Scrofuloderma *TB gumma *Orificial TB

Inoculation Inoculation Contiguous Hematogenous Autoinoculation

+/+ ++ ++ ++

+++ +++ +++ + +

+++ +++ ++ + -

Tuberculids *Papulonecrotic *Lichen scrofulosorum *Erythema induratum

Hematogenous “ “

-

+++ +++ +++

+++ +++ +++

Cutaneous Tuberculosis can be Classified as Given Blow 1. Inoculation tuberculosis (exogenous source): a. Tuberculous chancre b. Tuberculosis verrucosa cutis c. Lupus vulgaris (some). 2. Secondary tuberculosis (endogenous source) a. Contiguous spread— scrofuloderma b. Autoinoculation— orificial tuberculosis.

3. Hematogenous tuberculosis— acute miliary tuberculosis, lupus vulgaris (some), tuberculous gumma. 4. Eruptive tuberculosis (tuberculids) a. Micropapular— lichen scrofulosorum b. Papular— papular or papulonecrotic tuberculids c. Nodular— erythema induratum of Bazin, nodular tuberculid.

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TUBERCULOUS CHANCRE

LUPUS VULGARIS

It occurs due to inoculation of M. tuberculosis into the skin of an individual without natural or acquired immunity to tubercle bacilli. • Usually seen in face or limbs of children • Presents as a brownish red papule or nodule that ulcerates to form a ragged ulcer with undermined edge • Associated with regional lymphadenopathy • If untreated, chancre heals slowly over months.

It is the most common type of progressive cutaneous tuberculosis occurring in people with moderate or high immunity. • Lupus vulgaris arises from normal skin but it can arise in a scar of scrofuloderma. • The initial lesion is a reddish-brown, soft, gelatinous plaque which increases in size and extends peripherally. • Peripheral extension occurs with resultant scarring (Figs 13.1 and 13.2). • Diascopy reveals ‘apple jelly’ nodules in the periphery. • The various morphological forms are plaque type, ulcerative and mutilating form, vegetative form and tumor like. • Nasal mucosa can be involved leading to resultant destruction of nasal septum. • Rarely squamous cell carcinoma can occur.

MILIARY TUBERCULOSIS Miliary TB occurs due to hematogenous dissemination of tuberculosis in infants and children or immunosuppressed • The skin lesions are varied— may manifest as crops of bluish papules, vesicles, pustules or hemorrhagic lesions • Diagnosis established by skin biopsy which shows acid fast bacilli • The primary source of TB should be identified and treated.

Fig. 13.1: Lupus vulgaris—plaque lesion with active infiltrated border with central scarring over the thigh

Differential Diagnosis • Discoid lupus erythematosus— Lesions begin as dull red macules or indurated plaques that develop an adherent scale (carpet tack sign), mainly over head and neck and evolve with atrophy, scarring and pigmentary changes.

Fig. 13.2: Lupus vulgaris—verrucous plaque with trailing scar and depigmentation in the groin

Cutaneous Tuberculosis and Atypical Mycobacterial Infections • Lupoid form of cutaneous leishmaniasis may be impossible to distinguish clinically. Histopathology distinguishes them. • Deep mycoses may resemble vegetating form of lupus vulgaris. It can be differentiated by histology and culture reports. • Leprosy— nodules of leprosy are firmer compared to those of lupus vulgaris. Other signs of leprosy would help in distinguishing it from lupus. • Sarcoidosis— nodules of sarcoidosis resemble grains of sand on palpation and the surface is shiny and waxy. • Psoriasis - usually multiple lesions over the extensor aspect of limbs and lumbosacral areas, but are less infiltrated compared to lupus vulgaris. They are associated with silvery white micaceous scales and there is no evidence of scarring. • Lichen simplex chronicus of perianal area may mimic lupus vulgaris. There will be no scarring and it will be itchy and hyperpigmented rather than reddish brown in lupus vulgaris.

TUBERCULOSIS VERRUCOSA CUTIS (WARTY TUBERCULOSIS, ANATOMIST’S WART) Tuberculosis verrucosa cutis (TBVC) manifests as a warty growth that occurs as a result of

Fig. 13.3: Tuberculosis verrucosa cutis—verrucous plaque with fissuring and foetid discharge over the sole

inoculation of mycobacteria into the skin of a previously infected individual with moderate to high immunity. • Lesions occur in exposed areas such as foot (Figs 13.3 and 13.4), hand, ankle and rarely buttock. • The lesions start as warty papules that enlarge to a verrucous plaque with serpiginous border.

Differential Diagnosis • TBVC should be differentiated from other warty lesions such as verruca vulgaris, lupus vulgaris (usually not hyperkeratotic, diascopy demonstrates apple jelly nodules), chromoblastomycosis, hypertrophic lichen planus (has multiple itchy lesions usually over lower legs with evidence of lichen planus elsewhere), leishmaniasis and tertiary syphilis. SCROFULODERMA Scrofuloderma results from breakdown and involvement of skin overlying a tuberculous focus such as lymph node, bone, joint, epididymis or lacrimal gland. • It manifests as bluish red nodules overlying lymph nodes or joints that break down to form undermined ulcers with a bluish edge (Figs 13.5 and 13.6).

Fig. 13.4: Tuberculosis verrucosa cutis—verrucous plaque with fissuring over the dorsum of great toe

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Fig. 13.5: Scrofuloderma—subcutaneous nodules and ulcerated lesions along with scarring in the neck

Fig. 13.7: Scrofuloderma—sinuses and fistulae healing with puckered scarring over the back

by multiple sinuses, puckered scarring and formation of new nodules that lead to an uneven indurated lumpy surface. Pus containing sulphur granules discharging from multiple sinuses is quite characterstic, distinguishing it from scrofuloderma.

TUBERCULOUS GUMMA (METASTATIC TUBERCULOUS ULCER)

Fig. 13.6: Scrofuloderma—ruptured bluish nodules with undermined edges in the axilla

• The resultant sinuses and fistulae heal with puckered scarring (Fig. 13.7).

Differential Diagnosis • Scrofuloderma should be differentiated from hidradenitis suppurativa, acne conglobata, syphilitic gumma and actinomycosis. Cervicofacial actinomycosis is characterized

It occurs due to hematogenous dissemination during periods of bacillemia and lowered resistance • Common in poorly nourished children • Presents as firm subcutaneous nodules that soften and ulcerate to form undermined ulcers.

ORIFICIAL TUBERCULOSIS Tuberculosis of mucosa or skin adjoining orifices in a patient with advanced internal tuberculosis is known as orificial TB (Fig. 13.8). • The affected patient is usually an adult of poor general health

Cutaneous Tuberculosis and Atypical Mycobacterial Infections • Lesions occur in the mouth, tongue, or genitalia as reddish nodules that break down to form painful shallow ulcers with bluish undermined edges.

TUBERCULIDS Tuberculids are hypersensitivity eruptions which arise in response to an internal focus of tuberculosis and clear with antituberculous therapy.

Papulonecrotic Tuberculid • It is an eruption of necrotizing papules, particularly affecting extremities and occurring in more or less symmetric crops. • The lesions are hard, dusky papules that crust or ulcerate to heal with atrophic scars (Fig. 13.9). • Papulopustular secondary syphilis, pityriasis lichenoides et varioliformis acuta, ChurgStrauss granuloma, lymphomatoid papulosis, perforating granuloma annulare, perforating collagenosis and necrotizing or septic vasculitis share clinical and histologic features with papulonecrotic tuberculid.

• The lesions are localized to legs (calf region) of middle aged women with erythrocyanotic circulation. • It must be distinguished from erythema nodosum (short duration, rapid development, affects chiefly anterior aspect of the leg, more painful tender nodules that do not ulcerate), nodular vasculitis, polyarteritis nodosa, tertiary syphilis (gumma is usually unilateral and single, serology and histology helps), and other infectious and inflammatory panniculitis.

Diagnosis Absolute Criteria • Positive culture for M. tuberculosis • Guinea pig inoculation • PCR for M. tuberculosis.

Others • • • • • •

Proven TB elsewhere in the body Presence of AFB in the lesion Histopathology Positive tuberculin test (Fig. 13.12) Clinical history and physical signs Response to therapy.

Lichen Scrofulosorum • It presents as grouped, closely set minute perifollicular papules over the trunk (Fig. 13.10) or extremities in children with tuberculous disease • Lichen nitidus, lichen planus, secondary syphilis and sarcoidosis should be considered in the differential diagnosis. Erythema induratum • Presents as persistent or recurrent erythematous tender nodular lesions (Fig, 13.11) (usually ulcerate in contrast to erythema nodosum) that occur secondary to a tuberculous focus elsewhere.

Fig. 13.8: Orificial tuberculosis—painful, shallow ulcers with undermined edges around the anus

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Fig. 13.9: Papulonecrotic tuberculid—atrophic scars over the thigh following papulonecrotic tuberculid

Fig. 13.10: Lichen scrofulosorum—micropapular eruption over the trunk

Fig. 13.11: Erythema induratum—erythematous indurated tender noduloplaque lesion over the leg

Fig. 13.12: Positive Mantoux reaction

Treatment Anti tubercular therapy with three or four drugs is given for a period of 6 to 9 months based on the type of tuberculosis. Most regimens contain isoniazid, rifampin, ethambutol and pyrazinamide.

ATYPICAL MYCOBACTERIAL INFECTIONS Atypical mycobacteria can present with varied cutaneous features in normal as well as immunosuppressed patients. The main features are summarized in the following table.

Cutaneous Tuberculosis and Atypical Mycobacterial Infections

SUMMARY OF ATYPICAL MYCOBACTERIAL INFECTIONS Organism

Disease

Clinical Features

M.marinum

Swimming pool granuloma, fish tank granuloma

M.ulcerans

Buruli ulcer

Warty plaque or sporotrichoid lesions on knees, elbows and feet Subcutaneous nodules rupture to form shallow ulcers with necrotic fat in the floor Nodules, leg ulcers and papules Disseminated heterogenous infection in HIV patients Cellulitis and subcutaneous nodules Cutaneous abscesses, chronic ulcerative and nodular skin lesions, and cervical lymphadenitis

M.avium complex

M.chelonae Injection M.fortuitum abscess M. scrofulaceum Cutaneous abscesses

Treatment Rifampin and ethambutol or tetracycline Surgery is the treatment of choice followed by rifampin or cotrimoxazole Combined therapy of isoniazid, rifampin and streptomycin. Surgical debridement and amikacin or doxycycline or ciprofloxacin Treatment- surgical treatment of infected lymph node. Widespread disease- treatment same as in M avium complex

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14

Connective Tissue Disorders

The term “connective tissue disorders” (Collagen vascular disorders) encompasses a group of multi-system disorders which have certain features in common—the existence of autoimmunity in the form of antibody production or disordered cell mediated immunity, vascular abnormalities in the form of Raynaud’s phenomenon, occlusive vascular diseases or vasculitis, arthritis, arthralgia and skin disease. Involvement of skin is significantly predominant in this group of disorders. They are: systemic lupus erythematosus, systemic sclerosis, dermatomyositis, overlap-syndrome and mixed connective tissue disease.

LUPUS ERYTHEMATOSUS Lupus erythematosus (LE) is a multisystem disease of unknown origin characterized by the production of numerous diverse types of autoantibodies. Lupus erythematosus have wide spectrum of manifestations ranging from solitary chronic skin lesions in chronic discoid lupus erythematosus (DLE) to wide spread polymorphous lesions in subacute lupus erythematosus (SCLE) to multiple organ involvement in systemic lupus erythematosus (SLE).

DISCOID LUPUS ERYTHEMATOSUS (DLE) • Most common form of cutaneous lupus erythematosus. • Characterized by discrete, discoid, welldefined erythematous plaques covered with adherent scales (Figs 14.1 and 14.2). The lesions slowly expand with active inflammation at the periphery, leaving depressed scars, telangiectasias and permanent depigmentation (Fig. 14.3). • The central scarring with atrophy is very characteristic. • These lesions occur most often on the face, scalp, ears or neck. • Peeling the scale reveals an undersurface that looks like a carpet penetrated by several carpet tacks called “carpet tack sign”. • Scarring alopecia occurs in 60% of the cases (Fig. 14.4).

Types • Localized DLE: lesions occur only on the head or neck. • Generalized DLE: lesions are seen both above and below the neck (Figs 14.5 and 14.6).

Connective Tissue Disorders

Fig. 14.1: Discoid lupus erythematosus—well defined, discoid, erythematous plaques over the chest

Fig. 14.3: Discoid lupus erythematosus—discoid lesions evolving with central depigmentation and atrophy

Fig. 14.2: Discoid lupus erythematosus—discoid lesions involving the face

Fig. 14.4: Discoid lupus erythematosus—scarring alopecia

• Other types are hypertrophic, tumid, lupus erythematosus profundus, mucosal DLE, chilblain lupus, etc.

• The risk is higher in patients with disseminated DLE (22%).

Prognosis • DLE has a chronic progressive course. Patients with hematological and serological abnormalities have 6.5% risk of developing overt SLE.

Diagnosis • Based on clinical features and histopathology. Direct immunofluorescence (DIF)-deposits of IgG and C3 along the basement membrane in affected skin in up to 80%, but normal nonsun exposed skin always negative. Negative

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Essentials in Dermatology brown initially, later becoming red brown in color, have a characteristic translucence and woodgrains appearance, telangiectasia may be seen on the surface of the lesions, no prominent follicles), tinea faciei (KOH examination), granuloma faciale (brown color, no scarring), psoriasis (silvery scales), rosacea (pustules, ears spared) and Jessner’s lymphocytic infiltrate. In each case, histology is most helpful. The hypertrophic type of DLE may be confused with hypertrophic lichen planus, prurigo nodularis. LE profundus should be differentiated from other types of panniculitis. Mucosal DLE should be differentiated from mucosal lichen planus.

Fig. 14.5: Generalized discoid lupus erythematosus—discoid lesions involving the trunk

Fig. 14.6: Generalized discoid lupus erythematosus—discoid lesions involving the feet

or low titer ANA; sometimes higher titer in disseminated type. Exclude SLE.

Differential Diagnosis Lupus vulgaris (rarely symmetrical, has progression on one side and healing with scarring on the other side, apple-jelly nodules on diascopy), sarcoidosis (lesions are yellowish

Histopathology Characteristic histopathological changes are: • Hyperkeratosis with follicular plugging • Irregular atrophy of the stratum malphighi • Liquefactive degeneration of the basal cell layer and • Patchy perivascular and periappendageal lymphocytic infiltration. • Degenerative changes in the connective tissues—hyalinization, edema, fibrinoid change in the upper dermis. • Valuable clues are thickened periodic acidSchiff (PAS) positive basement membrane and deposition of mucin. Treatment • Photoprotection and topical sunscreens • Topical high potency or intralesional steroids • Topical calicineurin inhibitors (pimecrolimus, tacrolimus) • Systemic therapy for widespread recalcitrant disease are antimalarials (Hydroxychloroquine 200-400 mg daily or chloroquine 250 mg daily, monitoring by an ophthalmologist required every 6-12 months), dapsone (50-100 mg daily), thalidomide (50-200 mg daily), corticosteroids (prednisolone 40 mg

Connective Tissue Disorders daily short courses), oral auranofin, etretinate, isotretinoin, clofazimine, methotrexate, azathioprine, cyclophosphamide, etc.

SUBACUTE LUPUS ERYTHEMATOSUS (SCLE) • Characterized by scaly papules on the shoulders, extensor surfaces of the upper extremities, upper chest, upper back and neck in widespread and symmetric fashion. • Above lesions evolve into two morphological types either into papulosquamous or annular and polycyclic lesions. Rarely erythema multiforme-like with blisters (Rowell syndrome). • All patients with SCLE have mild systemic complaints and 50% of the patients fulfill the criteria for the diagnosis of SLE. • SCLE patients have antibodies to the cellular antigens Ro/SS-A and La/SS-B. • Children born to mother with SCLE may have congenital heart block (especially, those with anti Ro/SS-A antibody). • Differential diagnosis: To be differentiated from discoid lupus erythematosus, psoriasis, tinea corporis, annular erythemas, tinea versicolor and rarely erythema multiforme.

• It has been postulated that four or more genes are involved in predisposing an individual to SLE.

Pathogenesis LE is a multifactorial disease with genetic and immunopathologic abnormalities. The release of nuclear antigens because of enhanced apoptosis is a key factor. Important predisposing factors are genetic predisposition (HLA-B8, DR2, DR3, DQwl, DRB1), complement defects, exogenous factors (UV radiation, and medications), and individual factors (hormone status, altered immune status). The 1982 Revised Criteria for Diagnosis of SLE are: 1. Malar rash: Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds (Fig. 14.7). 2. Discoid rash: Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions.

Treatment Same as for discoid lupus erythematosus. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) SLE a multisystem disorder, primarily affects skin, joints and vascular system. The age of onset is usually between 16 and 42 years occurring more frequently in females (F: M:: 8:1).

Etiology • Exact cause is unknown but there is evidence to suggest the role of genetic, immune and various environmental factors.

Fig. 14.7: Systemic lupus erythematosus—malar and photosensitive rash over the face

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Essentials in Dermatology 3. Photosensitivity: Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation. 4. Oral ulcers: Oral or nasopharyngeal ulceration, usually painless, observed by a physician. 5. Arthritis: Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion. or 6. Serositis: a. Pleuritis—convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion. b. Pericarditis—documented by ECG or rub or evidence of pericardial effusion. 7. Renal disorder: a. Persistent proteinuria > 0.5 g/day or greater than 3+ if quantitation not performed or b. Cellular casts—may be red cell, hemoglobin, granular, tubular, or mixed. 8. Neurologic disorder: a. Seizures—in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance or b. Psychosis—in the absence of offending drugs or known metabolic derangements, e.g. uremia, ketoacidosis, or electrolyte imbalance. 9. Hematologic disorder: a. Hemolytic anemia—with reticulocytosis or b. Leukopenia < 4000/mL on two or more occasions or c. Lymphopenia < 1500/mL on two or more occasions or d. Thrombocytopenia—50% of patients. The onset of hypertension and/ or absence of upper limb pulses are often the complaints, which lead to a correct diagnosis. Polyarteritis Nodosa (PAN) This is rare in childhood, commonly occurs in adults. Clinical presentation of PAN is extremely variable. The initial symptoms can be rather vague and ill defined with fever, malaise and weight loss being prominent complaints. Hypertension is present in more than 80% of patients and the ESR is usually elevated. CNS involvement occurs in 50 to 70% of children and may first bring the patient to the attention of the physician. The other features that suggest the possibility of PAN are the presence of a typical livedo reticularis rash, abdominal pain, arthritis, myalgia and peripheral gangrene.

Kawasaki Disease (KD) KD is an acute systemic vasculitis of infancy and childhood. This clinical entity is also known as mucocutaneous lymph node syndrome. The clinical diagnosis of KD is usually quite straightforward, provided one keeps it in mind, whenever one encounters a young child with a febrile illness for which no other cause can be found. KD is a syndrome in which there is a constellation of clinical findings, which appear sequentially, with none of the features taken individually being of any significance. Diagnostic Criteria for Kawasaki Disease 1. Fever lasting for at least 5 days. 2. Presence of four of the following five conditions: i. Bilateral conjunctival injection ii. Changes of the mucosae of the oropharynx, including injected and/or fissured lips, strawberry tongue iii. Changes of the peripheral extremities such as edema and/or erythema of hands and/ or feet, desquamation usually beginning periungually iv. Rash, primarily truncal; polymorphous but non-vesicular v. Cervical lymphadenopathy 3. Illness not explained by other known disease process. Henoch-Schönlein Purpura (HSP) HSP is one of the most common vasculitides of childhood. HSP is a clinical diagnosis and is characterized by the presence of nonthrombocytopenic palpable purpura, arthralgia or arthritis, abdominal pain and gastrointestinal hemorrhage. These symptoms may occur over days to weeks. HSP is usually associated with vascular and renal deposition of IgA-containing immune complexes.

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Cutaneous Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis, Small Vessel Vasculitis) This is the most common form of vasculitis that exclusively affects capillaries and venules, almost invariably involves the skin. It is frequently associated with immune complex deposition (with underlying infections, drugs, malignancy, collagen vascular disorders, etc). This form of vasculitis has also been termed as hypersensitivity vasculitis. This small vessel vasculitis may be limited to the skin or may be associated with visceral involvement including pulmonary hemorrhage, intestinal ischemia or hemorrhage, and glomerulonephritis. Common manifestations include purpura and/or urticaria, abdominal pain, gastrointestinal bleeding or intussusception, arthralgias, arthritis or periarthritis, and glomerulonephritis. Visceral symptoms may precede the skin lesions, leading to diagnostic confusion. Purpura tends to occur in crops of lesions of similar age. Palpable purpuric lesions are generally more pronounced in gravitydependent areas like legs (Fig. 23.6). Papules, urticaria/angioedema, pustules, vesicles, ulcers, necrosis, and livedo reticularis may be seen. Paraneoplastic vasculitis is a term used to describe cutaneous necrotizing vasculitis with associated malignant conditions, including Hodgkin’s disease, lymphosarcoma, adult T cell leukemia, mycosis fungoides, myelofibrosis, acute and chronic myelogenous forms of leukemia, IgA myeloma, diffuse large cell leukemia, hairy cell leukemia, squamous cell bronchogenic carcinoma, prostatic carcinoma, renal carcinoma, and colon carcinoma. Urticarial vasculitis represents a peculiar subset of small vessel vasculitis, characterized by typical wheals or serpentine papules formation, sometimes with angioedema. Individual lesions are slower to resolve than typical urticaria and

often last for several days. There is frequently a burning sensation or discomfort from the lesions. These lesions often heal with skin discoloration—hyperpigmentation or an ecchymotic area. Most cases of urticarial vasculitis are idiopathic; they may be associated with an underlying autoimmune disorder such as SLE or Sjögren’s syndrome, IgM paraproteinemia (Schnitzler’s syndrome), viral infections (hepatitis, acute Epstein-Barr), and HenochSchönellein Purpura.

Microscopic Polyangiitis Microscopic polyangiitis (MPA) involves vessels ranging in size from capillaries and venules to medium-sized arteries. Glomerulonephritis, especially rapidly progressive glomerulonephritis, and alveolar hemorrhage are particularly common in MPA and uncommon in PAN. Antibody to myeloperoxidase, a type of PANCA, is detected in sera from 60 percent of patients with MPA. Benign Cutaneous PAN (BC PAN) BC PAN is a rare vasculitic entity mostly seen in adults. The appearance of painful, violaceous, palpable nodules or ridges of variable size along the course of arterioles characterize this relatively benign condition. Mild constitutional symptoms and arthritis of the weight bearing joints may occur. The exact etiology of this condition is not known. Wegener’s Granulomatosis (WG) WG is a potentially lethal, necrotizing, granulomatous angiitis affecting small and medium sized vessels with a predilection for the sinuses, nasal passages, pharynx, lungs and kidneys. In some instances, the lesions may be widely scattered and may involve the skin, heart, CNS, GI tract and joints. Constitutional symptoms such as fever and weight loss are usually quite prominent.

Skin in Systemic Diseases

Churg-Strauss Syndrome (CSS) (Allergic Angiitis and Granulomatosis) CSS, like WG, affects small- to medium-sized arteries and veins. Clinically, CSS and WG have similar patterns of organ involvement and pathology, especially in regard to upper and lower respiratory system disease and glomerulonephritis. CSS differs most strikingly from WG by its usual occurrence in patients with a history of atopy, asthma, or allergic rhinitis, which is often ongoing. In the prevasculitic atopy phase, as well as during the systemic phase of the illness, eosinophilia is characteristic and often of striking degree. Systemic features of CSS include some combination of pulmonary infiltrates, cardiomyopathy, coronary arteritis, pericarditis, polyneuropathy (symmetric or mononeuritis multiplex), ischemic bowel disease, eosinophilic gastroenteritis, ocular inflammation, nasal perforations, glomerulonephritis, and cutaneous nodules and/or purpura. Early diagnosis and prompt treatment (with corticosteroids or immunosuppressive drugs) can go a long way in decreasing the morbidity and mortality associated with these disorders. METASTATIC DEPOSITS OF MALIGNANCIES Five to ten percent of patients with cancer develop skin metastases. Usually metastases occur as numerous firm, hard or rubbery masses with predilection for the chest, abdomen, or scalp, in an adult over the age of 40 years who has had a previously diagnosed carcinoma. They are most commonly intradermal papules, nodules or tumors that are firm, skin colored to reddish, purplish, black or brown. Inflammatory carcinoma (carcinoma erysipeloides) is characterized by erythema, edema, warmth and a well defined leading edge similar to erysipelas

Fig. 23.7: Metastatic deposits of malignancies— Sister Mary Joseph nodules

in appearance. This is usually caused by breast carcinoma. The so-called Sister Mary Joseph nodule (Fig. 23.7) is formed by localization of metastatic tumors to the umbilicus. The most common primary sites are the stomach, large bowel, ovary and pancreas. Dissemination to the skin is often a late finding and metastases to other organs have usually occurred. A poor prognosis is thus the rule. Most cases of Hodgkin’s disease of the skin usually originate in the lymph nodes from which the extension to the skin is either retrograde through the lymphatics or by direct extension. Lesions present as papules or nodules with or without ulceration. Cutaneous B-cell lymphoma may present with solitary or multiple papules, plaques or nodules (Figs 23.8 and 23.9). The most common morphology of leukemic infiltration of the skin in all forms of leukemia is multiple papules or nodules or infiltrated plaques. They are rubbery on palpation and ulceration is uncommon. Extensive involvement of the face may lead to leonine facies.

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Fig. 23. 9: Metastatic deposits of malignancies— infiltrated nodules of lymphoma over the arm Fig. 23.8: Metastatic deposits of malignancies— infiltrated nodules and plaques of lymphoma over the abdomen

PARANEOPLASTIC DISORDERS Paraneoplastic disorders refer to cutaneous reaction patterns that have a statistical association with neoplasia of various internal organ systems. Schnyder criteria for paraneoplastic disorders: • No other explanation for skin findings. • Skin changes improve with cancer treatment and may reappear if cancer recurs. • Skin changes appear at about the same time as the systemic cancer: They may precede any clinical manifestation of the underlying malignancy. • Statistical connection is shown.

Paraneoplastic Disorders can be Categorized as 1. Disorders of Keratinization Acanthosis nigricans (AN) is characterized by velvety thickening and hyperpigmentation of the neck and body folds giving the skin a dirty appearance. It occurs in association with DM, obesity, internal malignancy and with certain

Fig. 23.10: Paraneoplastic disorders—rugose thickening of palms—tripe palms

drugs. Malignant acanthosis nigricans usually occurs in adults over 40 years of age. If differs from other forms of AN by its rapid onset and spread, and there is marked velvety hyperkeratosis and hyperpigmentation. There is more pronounced involvement of mucosa, perioral area, palms (tripe palms or acanthosis palmaris) and associated weight loss and wasting. Adenocarcinoma of stomach is most commonly associated with malignant AN.

Skin in Systemic Diseases

Acquired ichthyosis: Sudden onset of ichthyosis in adults should arouse the suspicion of internal malignancy. Associated neoplasms are nonHodgkin’s lymphoma, mycosis fungoides, multiple myeloma, carcinoma of breast, lung, cervix and liver.

Necrolytic migratory erythema (Glucagonoma syndrome) is caused by excessive production of glucagon by alpha cell tumor of pancreas. It is more commonly seen in women of 45-65 years. The skin lesions start as circinate, annular or arcuate erythematous plaques that spread peripherally with central clearing. Borders show vesicles, bullae, crusting and scaling giving polycyclic or geographical appearance. These lesions mainly localize around periorificial, acral, and intertriginous areas, closely resembling acrodermatitis enteropathica. Other features are glossitis, angular cheilitis, blepharitis, wasting, anemia, glucose intolerance. Zinc replacement, orctreotide, surgical excision of tumor gives cure only in 30% of cases, because of persistent metastasis.

Acrokeratosis of Bazex: This condition is characterized by symmetric, erythematous psoriasiform eruption mainly involving hands, feet, ears and nose. Nails are involved early and severely. It is commonly associated with carcinoma of pharynx, esophagus, tongue and lung.

Erythema annulare centrifugum usually idiopathic rarely associated with malignancies particularly myeloproliferative disorders. It is characterized by slowly expanding annular erythematous plaques with central clearing and scaling at trailing edge, commonly involves buttocks, thighs (Fig. 23.11), and upper arms.

Erythroderma is commonly associated with leukemia, lymphoma especially cutaneous T cell lymphoma (CTCL), and carcinoma of lung, liver, stomach, colon, pancreas and prostate. Erythroderma secondary to solid tumors may resolve after resection of the tumor.

3. Bullous Eruptions

Associated features may be Leser – Trelat sign, florid cutaneous papillomatosis, and pachydermoperiostosis. Malignant AN typically improves with treatment of underlying malignancy. Tripe palms is characterized by rugose thickening of the palms and accentuation of dermatoglyphic ridges (Fig. 23.10). It may occur alone or along with acanthosis nigricans. It is commonly associated with carcinoma of stomach, and lung.

Paraneoplastic pemphigus (PN) is a bullous disease characterized by severe and resistant

2. Migratory Erythemas Erythema gyratum repens is characterized by mobile, concentric, often palpable, erythematous, wave-like bands (migrating at the rate up to 1 cm per day), giving “wood grain appearance” to skin. A peripheral scale or collarete may be present, and frequently involves the trunk. Tumors associated are lung cancers, myeloproliferative disorders and many other solid cancers. Resection of the tumor may result in resolution of lesions.

Fig. 23.11: Paraneoplastic disorder—erythema annulare centrifugum over the thigh

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Essentials in Dermatology polymorphous mucocutaneous lesions. Pemphigus like, pemphigoid like, erythema multiforme like, graft versus host disease like and lichen planus like lesions occur. Associated neoplasms are Hodgkin’s lymphoma, chronic lymphocytic leukemia, Castleman’s tumor, and thymoma. Pemphigus vulgaris has well defined association with thymoma. Hodgkin’s lymphoma and many solid tumors have also been associated. Bullous pemphigoid is a subepidermal autoimmune bullous disease, mainly affecting elderly individuals characterized by large tense blisters over normal or erythematous skin distributed mainly over central abdomen and flexural aspect of limbs. Significant association with gastric carcinoma has been found. Adult linear IgA disease is a subepidermal bullous disease characterized by vesicles, bullae, and urticarial plaques mainly over trunk and extremities. An increased association with lymphomas has been found. Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by bullae, and vesicles at trauma prone sites. Association with myeloma and leukemia has been found.

mainly on the anterior surface of legs. It is usually associated with streptococcal infections, and sarcoidosis. Associated neoplasms are Hodgkin’s and non-Hodgkin’s lymphoma, leukemia and renal cell carcinoma. Subcutaneous fat necrosis has been reported in association with pancreatic carcinoma (mainly acinar cell type).

5. Collagen Vascular Diseases Dermatomyositis is an autoimmune disease characterized by inflammation of skin and skeletal muscles. Associated neoplasms are carcinoma of lung, ovary, stomach, pancreas, colon and lymphoma. Adults rather than children with dermatomyositis should be thoroughly investigated for underlying malignancy. Systemic lupus erythematosus is rarely associated with lymphoma or thymoma. Scleroderma was found to be associated with carcinoma of lung, but this could be due to lung tumor developing secondary to chronic pulmonary fibrosis.

Dermatitis herpetiformis is occasionally associated with intestinal lymphoma. Herpes gestationis has been described in association with hydatiform mole and germ cell tumor. Erythema multiforme like lesions occur in association with carcinoma, lymphoma and leukemia.

4. Panniculitides Erythema nodosum is characterized by crops of painful, erythematous nodules and plaques

Fig. 23.12: Paraneoplastic disorder—pyoderma gangrenosum

Skin in Systemic Diseases cancer. Generalized telangiectasias can occur with malignant angioendotheliomatosis and carcinoid tumors. Purpura: Lymphoma, acute leukemia, multiple myeloma can cause purpura. Vasculitis: Leukocytoclastic vasculitis is rarely associated with squamous cell carcinoma of bronchus, renal carcinoma, leukemia and lymphoma.

Fig. 23.13: Paraneoplastic disorder—Sweet’s syndrome lesions over the upper limb

6. Neutrophilic Dermatoses Pyoderma gangrenosum (PG) particularly bullous PG is associated with myeloproliferative disorders. Solid tumors such as carcinoma of colon, prostate, bladder breast, bronchus and ovary have also been reported in association with PG (Fig. 23.12).

Digital ischemia: Persistent digital ischemia often progressing to gangrene has been associated with carcinoma of pancreas, stomach, small bowel, ovary and kidney as well as with lymphoma. Monder’s disease is thrombophlebitis of anterior chest wall, which may be associated with breast cancer.

Sweet’s syndrome is characterized by abrupt onset of painful, tender, erythematous to violaceous plaques and nodules (Fig. 23.13) mainly over trunk and proximal extremities. Associated malignancies are acute myeloid leukemia (most common), other leukemias, multiple myeloma, and lymphoma, less commonly with carcinoma of testis, ovary, stomach, breast, prostate and rectum.

7. Vascular and Blood Abnormalities Flushing: Marked flushing of central face and upper trunk can be a feature of carcinoid syndrome. Palmar erythema can occur in liver failure secondary to either primary or metastatic tumor of liver. Telangiectasias: Localized, grouped telangiectasia of anterior chest wall may indicate breast

Fig. 23.14: Paraneoplastic disorder—wide-spread lesion of seborrheic keratoses over the trunk “Sign of Leser Trelat”

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8. Hormone Related Disorders Cushing’s syndrome: Tumors of lung and pancreas producing excessive ACTH can lead to Cushing’s syndrome. Hirsutism: Androgen secreting ovarian tumors can produce hirsutism. Gynecomastia: Estrogen secreting tumors of testis, lung tumor can cause gynecomastia.

9. Others Xanthomas: Diffuse plane xanthoma can be caused by multipl e myeloma.

Hypertrichosis lanuginosa acquisita refers to acquired excessive growth of lunugo (vellus) hairs mainly over face and ears but eventually over all hair bearing areas. It is usually associated with painful glossitis. Associated tumors are tumors of colon, rectum, bladder, lung, pancreas, uterus, breast, and lymphoma. Multiple eruptive seborrheic keratosis “Sign of Leser – Trelat” refers to sudden development of numerous often pruritic seborrheic keratosis, in association with internal malignancy (Fig. 23.14). Associated neoplasms are adenocarcinoma of GIT, breast, tumors of reticuloendothelial system, and transitional cell carcinoma of bladder.

Skin Changes of Pregnancy and Old Age

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Skin Changes of Pregnancy and Old Age

SKIN CHANGES OF PREGNANCY Skin changes occurring during pregnancy can be grouped into physiological variations, changes in pre-existing dermatoses, and pregnancy specific dermatoses.

Physiological Variations Physiological changes are most likely caused by hormonal changes. These include pigmentation of nipples, areolae (Fig. 24.1), and external genitalia. The linea alba becomes the linea nigra. Chloasma or melasma, a mask like hyper pigmentation of the face occurs in more than 50%

Fig. 24.1: Hyperpigmentation of nipple and areola with prominent Montgomery tubercles

of women. Pre-existing nevi or ephelides frequently darken during pregnancy. Mild to moderate hirsutism is frequently seen during pregnancy. After delivery, the resulting telogen effluvium may be severe, resulting in significant hair loss from 1 to 5 months postpartum. Striae distensae (Fig. 24.2) occurs in up to 90% of pregnant women. It is commonly seen over the abdomen, hips, buttocks, and sometimes breasts. Up to two-third of women develop palmar erythema and/or spider angiomas during pregnancy. Edema and varicosities commonly occur in hands and feet. Pregnancy epulis (granuloma gravidarum/pregnancy tumor of

Fig. 24.2: Striae distensae over the abdomen

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Essentials in Dermatology gingiva) is a pyogenic granuloma that may appear in the second or third trimester and resolves shortly after delivery.

Cholestyramine and ursodeoxycholic acid may be effective. Vitamin K to diminish the risk of postpartum hemorrhage can be given before delivery.

Changes in Pre-existing Dermatoses Acne, acne inverse, psoriasis and sarcoidosis tend to improve with pregnancy. Autoimmune collagen vascular disorders (lupus erythematosus, dermatomyositis, systemic sclerosis), autoimmune bullous diseases, invasive or metatastic melanoma, porphyria cutanea tarda, EhlersDanlos syndrome, pseudoxanthoma elasticum, viral and fungal infections tend to worsen. Atopic dermatitis and pustular psoriasis may improve or worsen.

Pemphigoid (Herpes) gestationis: It is the most specific dermatosis of pregnancy which is an autoimmune inflammatory bullous disease with onset during second trimester or during the postpartum period. Typically, pruritic urticarial papules and plaques develop around the umbilicus and extremities, which evolve into tense vesicles and bullae. Remit spontaneously usually within 3 months of delivery.

Pregnancy Specific Dermatoses Recurrent cholestasis of pregnancy (Prurigo gravidarum): It is a hepatic condition occurring late in pregnancy characterized by severe generalized pruritus that is often followed by the appearance of clinical jaundice. It has an estimated incidence of up to 2% of pregnancies. A slight increase in fetal mortality and prematurity has been reported. Postpartum hemorrhage is also more likely in these women. The condition remits within few days after delivery but tends to recur in subsequent pregnancies. Treatment includes bland emollients, topical antipruritic regimens, antihistamines, and UVB phototherapy.

Fig. 24.3

Pruritic urticarial papules and plaques of pregnancy (PUPPP): Also called as polymorphic eruption of pregnancy. It is a very common, intensely pruritic dermatosis that usually occurs late in the third trimester. It typically affects primigravidas. It is characterized by erythematous papules that begin in periumbilical striae distensae (Figs 24.3 and 24.4) and then spread to involve the buttocks and thighs yet spares the upper chest and face. Spontaneous resolution occurs most commonly few days after delivery.

Fig. 24.4

Figs 24.3 and 24.4: Pruritic urticarial papules and plaques of pregnancy involving striae and arms

Skin Changes of Pregnancy and Old Age

Fig. 24.5: Senile comedones over the face

Fig. 24.6: Cherry angiomas over the back

Topical corticosteroids form the main stay of management.

alone; photoaging (extrinsic aging), the superimposition on intrinsic aging of changes attributable to chronic sun exposure, which are preventable. Intrinsic aging changes include epidermal atrophy, reduced wound repair, few Langerhans cells and generally impaired immune response, decreased sensation and fewer hairs, decreased sweating, drier skin (less sebum and epidermal lipids) and less vascular reactivity. Chronic exposure to the ultraviolet (UV) component of solar radiation leads to photoaging which is characterized clinically by fine and coarse wrinkles, dyspigmentation (freckling and lentigines), telangiectasia, laxity, roughness and a sallow appearance. Light exposed skin may develop periorbital comedones (Fig. 24.5) (maladie de Favre et Racouchot), purpura, and venous lakes. Over a period of time, these extrinsic aging changes develop into solar elastosis, accelerated cell death and vascular changes (Fig. 24.6), actinic keratoses, basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Topical retinoids and hydroxyacids are the most effective treatment in preventing and partially reversing photodamage. A healthy balanced diet, avoidance of smoking, a good skin care regimen and regular exercise, coupled with sun protection in those with sensitive skin and outdoor lifestyles helps in preventing photoaging.

Prurigo gestationis (Besnier): It is a rare pruritic dermatosis that may occur any time during the fourth to ninth months of gestation. It is characterized by small papules that are excoriated on the proximal limbs and trunk. The eruptions tend to resolve quickly after delivery and it is uncommon to recur in subsequent pregnancies. Therapy with topical glucocorticoids is helpful. Impetigo herpetiformis: It is a form of pustular psoriasis that occurs during pregnancy and may be life-threatening. It tends to occur in third trimester of pregnancy. It is characterized by erythematous patches with peripheral pustules and central scaling favoring the abdomen and upper inner thighs. Systemic signs and symptoms include fever, chills, nausea and vomiting. The disease tends to remit promptly after delivery but may recur in subsequent pregnancies. Systemic glucocorticoids are the treatment of choice in impetigo herpetiformis.

SKIN CHANGES OF OLD AGE Cutaneous aging includes two distinct phenomena: Intrinsic aging, a universal, inevitable change attributable to passage of time

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Pediatric Dermatology

Some skin disorders are transient in newborn but make the parents nervous and anxious about their outcome, while other skin disorders develop later on during infancy or childhood. Some of these disorders are exclusive to children (Cradle cap, napkin dermatitis, acrodermatitis enteropathica, primary herpetic gingivostomatitis) while others are common in children (Pediculosis capitis, scabies, molluscum contagiosum, warts, chicken pox, tinea capitis, atopic dermatitis, oral thrush, Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, and papular urticaria).

Transient Cutaneous Lesions in Newborn • Vernix caseosa—golden yellow staining of vernix caseosa occurs in hemolytic disease of the newborn and post-maturity. • Acrocyanosis—cyanosis seen in acral areas in a neonate • Erythema neonatorum—within a few hours of birth- erythema fades spontaneously within 24-48 hours. • Harlequin color change—seen when the infant is placed on one side-upper half of the body becoming pale and the lower half a deep red color, with a sharp midline demarcation between the two, staying for half a minute to 20 minutes, in a full term or preterm newborn seen during first week of life.

• Cutis marmorata—this marbling change due to reticulate blue vascular pattern seen in infancy, occurs on exposure to decreased temperature and disappears on rewarming. • Physiological scaling of the newborn—seen in up to 75% of the normal neonates. • Sebaceous gland hyperplasia characterized by multiple, uniform, pin point yellowish papules, most prominent on the nose, cheeks, upper lip and forehead, but may be visible on the upper trunk, especially the areolae, genitalia and the limbs. This phenomenon is associated with milia which represents minute follicular epidermal cysts. • Linea alba becomes pigmented in about 8% of babies. • Exaggerated pigmentation of the scrotum occurs in about 30% of oriental neonates, generally associated with Mongolian spots. • Epstein pearls—are one or more 1-2 mm yellowish white keratinous cysts along the alveolar ridges or in the midline at the junction of the hard and soft palate. • Milia represent miniature epidermal inclusion cysts that originate from sebaceous apparatus of vellus hair (Fig. 25.1). Epstein pearls are clinically and histologically the intra-oral counterpart of facial milia.

Pediatric Dermatology

Fig. 25.1: Milia – tiny pearly white keratinous inclusion cysts over the face

• Succulent gums (Sucking pads)—a whitish hue to the oral mucosa. • Sucking blisters—blisters or erosions on the upper limb/upper lip, present at birth, due to intrauterine sucking. • Erythema toxicum neonatorum (Toxic erythema of the new born, erythema neonatorum)—presents as an asymptomatic macular erythema on the trunk within first 48 hours of birth. Subsequently, it may evolve into urticarial papules or pustules. Recovery occurs in 3 days. Smears of the pustule contents demonstrate inflammatory cells, more than 90% of which are eosinophils. There is an associated blood eosinophilia in 50% of cases. • Mongolian spots—are blue gray pigmentation areas present at birth on the sacral area of the normal infants in dark skinned races. Edwin Baez, thinking this as a characteristic of Mongolian race, named it as Mongolian spot. The Chinese people believed that the mark is the imprint of their “God of birth”. As the child is born, the God gives it a ‘spank’ or ‘kick’ to give it a start in life, whereas the

Japanese believed that the spot was the consequence of coitus performed during pregnancy. It usually disappears during the first decade and in a small percentage (3-4%) persist beyond this into adult life. • Acne neonatorum (Neonatal acne)— develops within the first 30 days of life. • Perianal dermatitis is an erythema centered on the anus, occasionally accompanied by erosion and bleeding at 4th to 7th day of life • Transient neonatal pustulosis (Transient neonatal pustular melanosis) invariably presents at birth. It is characterized by the presence of fragile superficial pustules mainly over the chin, neck, forehead, back, and buttock. Hyperpigmented macules develop subsequently. They may persist for 3 months and affected infants are otherwise normal. Pustules are formed due to subcorneal collection of neutrophils with a few eosinophils. Bacterial culture is negative. Pigmented macules demonstrate basal and supra-basal increase in pigmentation only, apparently without pigmentary incontinence.

Skin Disorders in Children (Pediatric Dermatoses) Skin disorders are extremely common in our population and approximately 6% of visits to all physicians entail a problem of the skin, hair or nails. However, dermatologists see only approximately 40% of these patients. Dermatological problems manifesting as primary and secondary cutaneous complaints, constitute at least 30% of all outpatient visits to a pediatrician and 30% of all visits to dermatologists involve patients of pediatric age group. The vast majority of complaints related to the skin in children can be easily recognized and treated by non-specialist. These common diseases have been classified in the Table 25.1.

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Essentials in Dermatology Table 25.1: Classification of common pediatric dermatoses 1. Infestations and infections (a) Parasitic infestations—Pediculosis capitis, scabies (b) Bacterial infections— Pyodermas (c) Viral infections—Molluscum contagiosum, warts, herpes simplex, chicken pox, herpes zoster (d) Fungal infections-Tinea capitis, tinea corporis, pityriasis versicolor, candidiasis 2. Dermatitis and eczema—Infantile seborrheic dermatitis, diaper or napkin dermatitis, atopic dermatitis, infective dermatitis 3. Urticaria 4. Exanthems—Viral exanthems (Measles, rubella, roseola infantum, erythema infectiosum) 5. Drug eruptions 6. Pigmentary disorders—Postinflammatory pigmentation, hypopigmentary disorders (Pityriasis alba, vitiligo, leprosy, nevus achromicus, ash leaf macule, albinism), hyperpigmentary disorders (Mongolian spots, café au lait macules) 7. Diseases of hair and nails—Tinea capitis, alopecia areata, diffuse alopecia, twenty nail dystrophy 8. Genetic diseases of the skin-Ichthyoses, acrodermatitis enteropathica 9. Collagen vascular diseases—Connective tissue diseases (Lupus erythematosus, scleroderma, and dermatomyositis) and vasculitic syndromes (Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, and polyarteritis nodosa) 10. Miscellaneous conditions—Papular urticaria, miliaria rubra, miliaria crystallina, psoriasis, hemangiomas, chilblains

SOME IMPORTANT VIRAL EXANTHEMS IN CHILDREN Measles (Rubeola, Morbilli) • The term measles is thought to come from Latin “misellus” or “misella”, a diminutive of Latin “miser”, meaning miserable. • It is caused by measles virus (a paramyxovirus, RNA virus). • Incubation period is 10-11 days. • Measles, is a universal highly contagious disease of children. It has a characteristic prodrome of 3-4 days that consists of high fever, cough, coryza, a striking palpebral conjunctivitis with photophobia, and Koplik’s spots, which precede the appearance of florid generalized macular and papular rash. • The first lesion to appear on the soft palate is blotchy erythema, but the most pathognomonic lesion of the prodrome, if present are Koplik’s spots, which appear as tiny white lesions surrounded by an erythematous ring (grain of sands). • Koplik’s spots precede the onset of generalized rash by 1-2 days, remain for two to three days

•

• •

•

and are usually heavily clustered on the buccal mucosa opposite the second molar. The purplish red rash on the body appears first behind the ears and over the forehead, and then spreads slowly to involve the entire body by third day. The eruption extends downwards over the neck, shoulders and trunk and then distally over the upper and lower extremities. The rash fades with brown pigmentation followed by desquamation. Uncomplicated measles runs a self limited course lasting about 10 days. Complications of measles include encephalitis, thrombocytopenia, otitis media, pneumonia, exacerbation of tuberculosis and subacute sclerosing panencephalitis. There is no specific therapy for measles.

Rubella (German Measles) • Rubella virus is a togavirus, commonly recovered from pharynx. • Incubation period is 14-21 days. • Rubella is a common communicable infection of children and young adults characterized by a short prodromal period; enlargement of

Pediatric Dermatology cervical, suboccipital and postauricular glands and a rash of approximately 2 to 3 days duration. • An enanthem, Forschheimer’s sign, is present in up to 20% of patients during the prodromal period or on the first day of the rash. Dull-red macules or petechiae are confined to the soft palate. • The disease has rare sequelae apart from devastating effect on the fetus.

Exanthem Subitum (Sixth Disease, Roseola Infantum) • Caused by Human herpes virus type 6 (DNA virus). • Incubation period is 10-15 days. • Most common exanthem with fever in children under age group of 2 years. • Prodromal fever is usually high. Fever drops on fourth day. • Convulsions and lymphadenopathy may accompany it. • Clinically, a morbilliform erythema consisting of rose colored discrete macules appears on the neck, trunk, and buttocks. • Often there is a blanched halo around the lesions. • The lesions resolve in 1 to 2 days. • Other common associated findings include otitis media, diarrhea and meningoencephalitis. • In adults HHV-6 infection resembles acute infections mononucleosis. • Treatment – acyclovir, ganciclovir. Erythema Infectiosum (Fifth Disease) • Exanthematous disease occurring in patients with primary human parvo virus B19 infection (DNA virus). • Incubation period is 4-14 days. • More commonly seen in school children.

• Infection spreads by respiratory droplets during the prodrome. • Constitutional symptoms are absent or very minimal.

Three Stages of Rash are 1. “Slapped cheek” appearance (1 to 4 days). 2. Erythematous papular eruption over the upper and lower extremities spreading to trunk. Assumes a lace-like or reticulated appearance as it fades. 3. Recurrent evanescent stage (for weeks or months) is precipitated by a variety of skin irritants such as sunlight, hot showers. • Papular – purpuric ‘ gloves and socks’ syndrome seen in older children and adolescence. • Adults may present with atypical rash and arthritis. • Complication—Hydrops foetalis (maternal infection) and aplastic crisis. • Treatment—supportive.

Gianotti-Crosti Syndrome • Infantile papular acrodermatitis, or the Gianotti-Crosti syndrome, presents with symmetric erythematous lichenoid papules on the face, extremities, and buttocks, usually sparing the trunk. • The eruption is not pruritic and may be accompanied by splenomegaly, hepatitis, and lymphadenopathy. • The process often occurs in young children after an upper respiratory tract illness. • Pathologic specimens show a perivascular infiltration of lymphocytes and histiocytes in the upper portion of the dermis. • While the syndrome has been associated with hepatitis B and enterovirus infection, several cases have been associated with acute EBV infection.

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SOME OTHER IMPORTANT ENTITIES Henoch Schönlein Purpura • Henoch Schönlein purpura is an IgA mediated vasculitis syndrome affecting skin, joints, GIT and kidneys. • It usually occurs below the age of 20 years. • The eruption may begin as crops of palpable purpuric lesions or urticarial rash in the lower legs and buttocks. • Abdominal symptoms such as colic, vomiting and diarrhea are seen in two-third of the patients. • Polyarthralgia is seen in most patients, commonly affecting the knees and ankles. • Renal involvement is usually mild, consisting of proteinuria/hematuria, but can rarely lead to end stage renal disease. • Diagnosis: Histopathology shows leucocytoclastic vasculitis and immunoflorescence demonstrates IgA deposition around blood vessels. • Treatment: No specific treatment available. Antibiotics and corticosteroids can be given to alleviate symptoms.

Fig. 25.2

Urticaria Pigmentosa Urticaria pigmentosa is the most common type of cutaneous mastocytosis that occurs due to the accumulation of mast cells in the skin. • The skin lesions are itchy small, yellow tan to reddish brown maculopapules/plaques/ nodules scattered all over the body (Figs 25.2 and 25.3). • Mild trauma such as scratching or rubbing the lesions may cause urtication and erythema around macules and this is known as Darier’s sign. • Urticaria pigmentosa is associated with pruritus which may be exacerbated by temperature, friction, spicy foods, alcohol and drugs. • Diagnosis: Histopathology shows mast cell infiltration in the dermis • Treatment: Avoidance of precipitating factors and antihistaminies. Langerhans Cell Histiocytosis (LCH) Langerhans cell histiocytosis is a disease that results due to the proliferation of cells like Langerhans cells, called as LCH cell (share the

Fig. 25.3

Figs 25.2 and 25.3: Urticaria pigmentosa—multiple brownish pigmented infiltrated lesions over trunk and extremities

Pediatric Dermatology

Fig. 25.4: Letterer-Siwe disease–seborrheic dermatitis like rash involving scalp extending on to forehead and ears

Fig. 25.5: Letterer-Siwe disease—hypopigmented macular as well as purpuric papular lesions seen over the abdomen

ultrastructural features with Langerhans cellscontaining Birbeck granules) in any organ. This “LCH cell” is about four to five times larger than small lymphocytes; has an irregular and vesiculated nucleus; is often reniform (kidney shaped); and has abundant, slightly eosinophilic cytoplasm.

Fig. 25.6: Letterer-Siwe disease—marked hepatosplenomegaly

• It is broadly classified into entities such as Letterer-Siwe disease, Hand-Schüller Christian disease and eosinophilic granuloma. • Eosinophilic granuloma occurs due to localized proliferation of “LCH cells” in the bones, skin, lymph nodes, lung, liver and spleen . • Hand-Schuller-Christian syndrome is a chronic multisystemic disease known by the triad of exophthalmos, multiple skull lesions and diabetes insipidus. • Letterer-Siwe disease is usually seen in children less than 1 year. It is characterized by seborrheic dermatitis like rash (Fig. 25.4) with hemorrhagic papular (Fig. 25.5), vesicular, pustular and ulcerated lesions in the intertriginous regions and trunk. • Letterer-Siwe disease is often associated with hepatosplenomegaly, dysfunction of liver, lungs and hematopoietic system. Lytic lesions may be seen in skull bones (Fig. 25.6). • Diagnosis: Histopathology shows LCH cell infiltration of the lesions. • Treatment: Localized forms can be treated with intralesional steroids or surgery. Multisystemic involvement needs chemotherapy.

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Benign, Pre-malignant and Malignant Tumors of the Skin

Skin tumors can be broadly classified into various types based on cell of origin. Broadly they can be classified as benign, premalignant and malignant tumors. Some of these common cutaneous tumors are discussed in this chapter.

BENIGN SKIN TUMORS Seborrhoeic Keratosis (Senile Wart, Senile Keratosis, Seborrheic Verruca, Basal Cell Papilloma) • A benign tumor, more common in the elderly people. • Seborrheic keratosis (SK) occur on any body site, most frequent on the face and the upper trunk. • Seborrheic keratoses typically begin as flat, sharply demarcated, brown macules. Follicular prominence is one of the hallmarks of seborrheic keratoses. Later on, typical asymptomatic, slowly increasing, verrucous plaque develops and have a “stuck-on” appearance. • Surface of SK has loosely adherent greasy keratinous scales on the surface. • Sometimes, sudden eruptive lesions appear which may be due to underlying malignancy. Then it is called ‘Leser-Trelat sign’. • Classical SK shows features of hyperkeratosis and numerous horn cysts in histology.

• Treatment – curettage, cryotherapy or electrodessication.

Naevi • The word naevus is derived from the Latin term meaning spot or blemish, originally used to describe the congenital lesion or birth mark (Mother’s mark). • In modern usage, it denotes a cutaneous hamartoma or benign proliferation of cells. • Nevi can be broadly classified into various types according to the predominant cell type. • The various types are keratinocyte nevi (Figs 26.1 and 26.2), follicular nevi, sebaceous nevi, apocrine nevi, eccrine nevi, connective tissue nevi, smooth muscle nevi, elastic nevi, fat nevi (Fig. 26.3), and vascular nevi (Figs 26.4 to 26.7).

Melanocytic Nevi • They are benign tumors derived from melanocytes. They are broadly classified into acquired or congenital. • Acquired melanocytic naevi are subdivided into junctional, compound (Figs 26.8 and 26.9) and dermal. • They begin as proliferative naevus cells along the dermal-epidermal junction (forming a junctional naevus)

Benign, Pre-malignant and Malignant Tumors of the Skin

Fig. 26.1

Fig. 26.2

Figs 26.1 and 26.2: Nevus—verrucous epidermal (keratinocyte) nevus occurring on one side of the body

Fig. 26.3: Nevus-nevus lipomatosus cutaneous superficialis presenting as lobulated mass over the thigh

• With continued proliferation, they extend from the dermal-epidermal junction into the dermis (forming a compound naevus). • The junctional component of the melanocytic naevus may resolve leaving only an intradermal component (intradermal naevus). • Acquired melanocytic naevi may resolve spontaneously.

Fig. 26.4: Nevus—Portwine stain over the face

• Congenital melanocytic nevi may be defined as melanocytic naevi present at birth (Figs 26.10 to 26.13). • Those measuring more than 20 cm in greatest diameter are referred to as Giant congenital melanocytic nevi or bathing trunk nevi. • Treatment: surgical excision.

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Fig. 26.5

Fig. 26.6

Figs 26.5 and 26.6: Nevus—Hemangioma of infancy over the nape of neck and face

Fig. 26.7: Angiokeratoma circumscriptum of the tongue

Fig. 26.8: Melanocytic nevus—compound nevus over the cheek

Skin Tags (soft warts; Acrochordons) • Common benign lesion, occurs on the neck, axilla and groin • The lesions are round, soft, pedunculated connected to the skin by a narrow pedicle.

They vary in size from 1 mm to 1 cm long (Fig. 26.14). • The skin tags are of three types which include–multiple small furrowed papules (12 mm long), single or multiple filiform

Benign, Pre-malignant and Malignant Tumors of the Skin

Fig. 26.9: Halo nevus over the cheek

Fig. 26.10: Congenital melanocytic nevus over the face of a child

smooth growths (2-5 mm) and solitary baglike–pedunculated growth (1 cm). • Histopathologically skin tags consist of loose fibrous tissue covered by folded skin. • They have been found in association with colonic polyps, diabetes and acromegaly. • Simple snipping, electrocautery and cryotherapy are effective.

Fig. 26. 11: Congenital melanocytic nevus with hairiness over the back

Pyogenic Granuloma (Granuloma pyogenicum) • They are smooth surfaced, bright red, friable, sessile or pedunculated lesions of exuberant granulation tissue with a pale epidermal collarette around the lesion (Fig. 26.15) • Occurs following a minor injury or infection of the skin • They most often affect children or young adults • The hands, fingers and face especially the lips and gums are the most common sites. • The lesion once developed may persist indefinitely unless destroyed. It may occur in pregnancy in gingiva–called as “Epulis Gravidarum” or “Pregnancy tumor”. • Differential diagnosis includes Kaposi’s sarcoma and bacillary angiomatosis • Treatment: excision and electrofulguration. Milia • They are tiny, white, globoid cysts that commonly occur on the face around eyes (Fig. 26.16). • Primary milia represent a keratinizing benign tumor. They arise spontaneously on the face in the predisposed individuals.

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Fig. 26.12

Fig. 26.13

Figs 26.12 and 26.13: Dermal melanocytosis—Nevus of Ota in the periorbital area with scleral pigmentation

Fig. 26.14: Skin tags—pedunculated soft lesions in the axilla

Fig. 26.15: Granuloma pyogenicum—pink colored nodule bleeds on manipulation

• Secondary milia are type of retention cyst that arises due to damage to the epithelium and occurs in diseases like bullous pemphigoid, porphyria cutanea tarda and others following trauma. • Treatment: Deroofing with hypodermic needle, trichloroacetic acid cautery or electrocautery.

Trichoepithelioma • Trichoepithelioma is benign appendageal tumor with follicular differentiation. • They appear at puberty as solitary or multiple, skin colored, translucent, rounded nodules on the face (Fig. 26.17). • The lesions are distributed predominantly in the nasolabial folds and eyelids.

Benign, Pre-malignant and Malignant Tumors of the Skin

Fig. 26.16: Milia—white keratinous cysts over the face

Fig. 26.18: Syringomas—multiple angulated papular lesions in the periorbital area

• Clinically lesions are multiple, skin colored, 1-3 mm sized, angular papules (due to, numerous small cystic ducts, as well as solid epithelial strands in the upper dermis and mid-dermis) distributed bilateral symmetrically, most commonly on the lower eyelids (Fig. 26.18), less commonly over the chest and neck. • Treatment with diathermy produces good results.

• A few telangiectatic vessels are often present on the surface of the large lesions, which resemble basal cell carcinoma. • Treatment with diathermy produces good results.

Hypertrophic Scar • Injury or surgery in a predisposed individual can result in an abnormally large scar called as hypertrophic scar • A hypertrophic scar represents excessive collagen deposition at the site of wound healing • Typically, hypertrophic scar starts as an asymptomatic, erythematous, smooth, firm scar seen at anatomic locations characterized by high tensions. With time, they flatten and become white in color. • Hypertrophic scars do not extend beyond the limits of the original trauma and heal by 6 months.

Syringoma • Benign tumors of eccrine differentiation • More common in females

Keloids • Keloids represent exaggerated collagen deposition at the site of wound healing.

Fig. 26.17: Trichoepithelioma—multiple skin colored translucent rounded nodules in the nasolabial folds

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Fig. 26.19: Keloid—indurated skin lesion showing peripheral extensions

Fig. 26.20: Dermatofibroma—single skin colored tender nodule over the shoulder

• They frequently proliferate beyond the wound margins onto the normal adjacent skin (Fig. 26.19). • A keloid appears as a firm, mildly tender, bosselated tumor present at a site of previous injury. They are commonly pruritic, erythematous, indurated lesions that show extensions like claws of a crab. They may even be the source of significant discomfort or pain. • They rarely undergo involution. • Treatment: Medical–topical steroids, intralesional steroids and silicone gel dressings. Surgical-surgical excision, cryosurgery and skin grafts.

Glomus Tumor • This arises within the glomus body, a neuromyoarterial receptor (the SucquetHoyer canal) that is sensitive to temperature variations and regulates arterial blood flow. • These tumors, more common on the fingers and toes and beneath the nail plate. • Usually seen in young adults between the third and fourth decade of life. • They can be solitary or multiple. • Classically presents as solitary, small, blue – red nodules on the hand (nail bed) that are characteristically associated with paroxysmal pain often elicited by changes in temperature. • Simple excision- treatment of choice.

Dermatofibroma • Most common benign dermal fibrous tumor. • Typical dermatofibromas appear as skin coloured to red-brown, firm, tender nodule(s), most commonly seen on the extremities (Fig. 26.20) • Lateral compression of the lesion with fingers results in the depression on the top–called ‘dimple sign’ • Histologically the fibroblasts and collagen bundles are arranged in a storiform or cartwheel pattern • Treatment of choice–simple excision.

PREMALIGNANT EPIDERMAL TUMOURS Actinic Keratosis (Senile or Solar Keratosis) • Most common premalignant skin tumor. • These lesions occur in sun-damaged skin of elderly people having light complexion • Clinically, these lesions are round to irregular keratotic papules surrounded by erythema.

Benign, Pre-malignant and Malignant Tumors of the Skin

Fig. 26.22: Erythroplasia of Queyrat—sharply defined brightly erythematous velvety plaque over the glans penis

Fig. 26.21: Actinic keratoses—Albino showing a number of actinic keratoses lesions along with two basal cell carcinoma lesions over the face

• The principal sites are the back of the hands, forearms and face (Fig. 26.21). • Squamous cell carcinoma can develop from actinic keratosis. • Histologically, there may be vacuolization of keratinocytes with numerous mitotic figures seen involving the lower layers of the epidermis (carcinoma in situ). • Treatment: Medical – topical tretinoin and topical 5-fluorouracil and surgical- curettage, electrodessication and cryotherapy.

Erythroplasia of Queyrat • This condition affects uncircumscised males. • Seen in the fifth and sixth decades of life. • The lesions present as sharply defined, brightly erythematous and velvety plaque with moist glistening or granular surface over the glans penis (Fig. 26.22). • Differentiated from benign inflammatory dermatoses such as psoriasis, lichen planus, Zoon’s plasma cell balanitis and fixed drug eruptions.

• Treatment with topical 5-fluorouracil produces satisfactory results.

Bowen’s Disease • Refers to cutaneous plaques of intraepidermal squamous cell carcinoma. • Chronic sunlight exposure, inorganic arsenicals are important etiologic factors. • Clinically lesions of Bowen’s disease appear as solitary, sharply defined, round or oval to irregular erythematous psoriasiform or eczematous plaque. • Ulceration is a sign of development of invasive carcinoma. • Histology shows proliferating atypical squamous cells through the full thickness of the epidermis (“wind- blown appearance”) • The most effective treatment for Bowen’s disease is surgical excision. Cutaneous Horn (cornu cutaneum) • Cutaneous horn (cornu cutaneum) is the term coined for horny skin excrescence, which in its form and consistency resembles an animal horn in miniature (Fig. 26.23) • The paramount consideration while making a clinical diagnosis is the height of the

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Fig. 26.23: Cutaneous horn—horny excrescence resembling an animal horn in miniature

•

• • •

keratotic mass (at least one half of its largest diameter). It is a reaction pattern of exaggerated hyperkeratosis and is rarely, if ever seen nowadays. Its association with various dermatoses may be informative. The important issue is not the horn itself which is dead keratin, but rather the nature of underlying condition, which may be benign (seborrheic keratoses, viral warts, histiocytoma, inverted follicular keratosis, verrucous epidermal nevus, organoid nevus, ichthyosis hystrix, palmoplantar keratoderma, papilloma, keratoacanthoma, open epidermoid and trichilemmal cysts, lichen planus, corn and calluses, scar, molluscum contagiosum), premalignant (solar keratosis, arsenical keratoses, Bowen’s disease) or malignant (squamous cell carcinoma, rarely, basal cell carcinoma, metastatic renal carcinoma, granular cell tumor, sebaceous carcinoma or Kaposi’s sarcoma). In the majority of cases, these horns are benign. Most commonly, they are single and arise from a seborrheic keratosis lesion. They are encountered most frequently on the face and scalp, but may occur on the hands, penis and eyelids.

Basal Cell Carcinoma (BCC) (Rodent Ulcer) • Most common malignant skin tumor that rarely metastasizes. • It is a malignant tumor of the skin that is believed to arise from the hair follicle. • Its cells show a morphologic resemblance to the relatively undifferentiated cells of the basal layer of the epidermis. • BCC is more common in men. • Persons with fair complexion, having outdoor occupation and chronic sun exposure are at a higher risk to develop BCC. • The five clinical forms of BCC include–the noduloulcerative (most common), superficial type, pigmented type, sclerosing type and fibroepithelioma. • The most common clinical presentation of BCC is the noduloulcerative type, which appears as a dome-shaped papule with a telangiectatic surface and a “pearly” translucent border (Figs 26.24 and 26.25). It begins as small, shiny, waxy nodule increases in size, undergo central ulceration • It is locally invasive without any metastasis to regional lymph nodes • Treatment- surgical excision, electrodesiccation, irradiation. Kaposi’s Sarcoma • Kaposi’s sarcomas (KS) are multisystem vascular neoplasms, characterized by mucocutaneous violaceous lesions and edema as well as involvement of nearly any organ • Human herpes virus type 8 has been implicated in the pathogenesis • KS have been classified into five typesClassical type, African-endemic type, iatrogenic type, immunosuppression associated type and HIV associated type (Epidemic type)

Benign, Pre-malignant and Malignant Tumors of the Skin

Fig. 26.24

Fig. 26.25

Figs 26.24 and 26.25: Basal cell carcinoma—ulcerated nodule over the eyelid showing pearly translucent border with telangiectasia

• Presents as ecchymotic macules, which become purple and brownish with hemosiderotic halo. The lesion evolves into patches, plaques and nodules and are often arranged parallel to skin tension lines. • Classical KS lesion occurs on the leg at the mean age of 60 years. • Oral lesion can be the first manifestation of KS in the majority of cases, especially in those having underlying HIV infection. • Histologically, a characteristic sign of KS is the presence of solid cords and fascicles of oval or spindle shaped cells arranged between the jagged vascular channels. These structures dissect the collagen bundles of the entire dermis, leaving a spongy network of collagen. This biphasic tumor morphology, exhibiting both angiomatous and solid tumor patterns, changes to a clear-cut sarcomatous morphology. • Modalities of management include— radiation and chemotherapy.

Mycosis Fungoides Mycosis fungoides is a form of cutaneous T- Cell lymphoma (CTCL). • It is a chronic, slowly progressive disease that evolves from patches (patch stage) (Fig. 26.6)

to plaques (plaque stage) and subsequently nodules (tumor stage). • Pruritus is a prominent symptom. • The lesions coalesce and may ulcerate, leading to deep ulcers. • Prognosis depends upon the TNM staging. • Diagnosis: Clinically lesions can be confused with eczema and psoriasis. Histopathology reveals atypical lymphocytes infiltrating the epidermis without spongiosis (epidermotropism). The pathognomonic feature is presence of Pautrier microabscess (collection of atypical lymphocytes in the epidermis). The dermis has dense monomorphous lymphomononuclear infiltrate with grenz zone. • Treatment: It depends on the stage of the disease. Chemotherapy, retinoids, electron beam therapy, photochemotherapy, etc. have been used.

Sézary Syndrome Sézary syndrome is a rare special variant of cutaneous T-cell lymphoma characterized by a triad of features—erythroderma, peripheral lymphadenopathy and infiltrates of atypical cells in the skin and blood.

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Fig. 26.26: Mycosis fungoides—multiple hypopigmented patches over the chest and abdomen

Fig. 26.27: Sézary syndrome—face showing erythematous infiltrated plaques, in addition to diffuse erythema

• It occurs in people older than 60 years and more commonly in males. • There is generalized erythroderma (Fig. 26.27) with diffuse hyperkeratosis of palms and soles and diffuse hair loss.

• Peripheral smear shows more than 10% atypical lymphocytic cells in the blood. • Treatment is chemotherapy combined with electron beam therapy or photochemotherapy.

Topical Formulary and Key Systemic Drugs

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Topical Formulary and Key Systemic Drugs

The use of topical remedies in the treatment of disease is as old as medicine itself. Because the skin is accessible and visible, it is uniquely amenable to external chemical and physical remedies.

Acute Exudative Dermatoses (Erythema, edema, vesiculation, oozing, crusting, infection, pruritus)

KEY POINTS IN TOPICAL THERAPY From treatment point of view, most of the common dermatoses fall into one of the two categories. 1. Dry dermatoses 2. Wet dermatoses The popular saying in treatment is “If the skin is dry, wet it, or if the skin is wet, dry it”. The most effective way to “dry” skin that is involved with acute exudative dermatoses is to apply cool, wet compresses with or without astringents, followed by open air or absorbent powders. Hence, for this use lotions (aqueous solutions) or gels are the vehicles of choice rather than ointments. Conversely, the effective way to “wet” the skin as in case of xerosis or chronic inflammatory and papulosquamous skin lesions is to apply greasy ointments, water in oil ointments or occlusive wrappings.

Chronic Inflammatory Dermatoses (Erythema, scaling, lichenification, dryness, pruritus) The term “vehicle” is used for those substances that bring specific drugs in contact with the skin. An ideal vehicle 1. Easy to apply and to remove. 2. Non-toxic. 3. Non-irritant. 4. Non-allergenic. 5. Chemically stable. 6. Homogeneous.

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Essentials in Dermatology 7. Bacteriostatic. 8. Pharmacologically inert. 9. Cosmetically acceptable. For a layman, it should not “Sting, stale/ stench and stain” For any drug to be effective topically, it must be formulated at the proper concentration and in the proper vehicle. In general, the most important vehicles for topical use may be divided into monophasic, biphasic, and triphasic forms. There are three basic constituents of a formulation, which are present singly or in combination to form a vehicle. They are: 1. Powders. 2. Greases. 3. Liquids. When only one of the basic constituent is present in a formulation vehicle, then it is called monophasic vehicle (Powders, liquids or greases/ oils). In case two of them are present, it is called biphasic vehicle(The combination of powder with water gives either a drying paste or a shake lotion. Grease or oil and powder will form either a liniment or a protective (fatty) paste. Water and grease, however, will mix to form emulsions in the presence of a surfactant or emulsifier. These then form oil in water (O/W) or water in oil (W/O) creams) and if all the three are present, it is called triphasic vehicle (Cooling pastes and cream pastes are triphasic vehicles that consist of oil-water-powder mixtures in varying proportion).

TERMINOLOGY IN TOPICAL FORMULATION Wet dressings are water or saline soaked cotton gauze or cloth compresses used in the treatment of acute inflammatory dermatoses with oozing, weeping and crusting, bullous diseases and ulcers.

Baths/soaks are a mode of drug delivery wherein a part (soak) or the whole body (bath) is immersed in medicated water. Lotions are liquid formulations where the active ingredient is present as powder suspended in aqueous solution by aid of a suspending agent known as shake lotion (need to be shaken before use) or active ingredients are dissolved to clarity called as clear solutions. Gels are soft semisolid preparations that are translucent to transparent in appearance. They liquefy on contact with the skin and dry to leave behind a thin greaseless film and are appropriate for use on hairy areas. Tinctures are alcoholic solutions with low concentration of active ingredients, e.g. tincture iodine. Paints are medicated solutions which leave a colored film on drying of the aqueous phase, i.e. they cause staining, e.g. gentian violet paint, Castellani’s paint. Ointments are semisolid soft to very firm greasy preparations and employ lipophilic bases. Petrolatum and white petrolatum are the most widely used ingredients in the ointments. Creams are semisolid soft to moderately firm washable emulsions and are generally of the oil in water type. Pastes are preparations of about 50% powdered ingredients in a greasy base such as petrolatum. Water based preparation of powder form drying pastes. One gram of cream covers an area approximately 10 by 10 cm. An ointment spreads up to 10 percent further. According to Arndt, the amount needed for the single application of a cream or ointment to the face or hands is 2 gm; to one arm or the anterior or posterior trunk, 3 gm; to one leg, 4 gm; and to the entire body, 30 gm.

Topical Formulary and Key Systemic Drugs

KEY SYSTEMIC DRUGS—PENICILLINS Originally derived from Penicillium notatum are Beta-lactam antibiotic, inhibits transpeptidases by binding to penicillin binding proteins (PBPs) and thereby interferes with bacterial cell wall synthesis. Natural penicillins are benzyl penicillin (Penicillin G), sodium penicillin G (crystalline penicillin), and repository penicillin G (given deep IM) (such as procaine penicillin G, and benzathine penicillin G). Semisynthetic penicillins – 1. Acid resistant alternative to penicillin G – phenoxymethyl penicillin (Penicillin V). 2. Penicillinase resistant penicillins – methicillin, oxacillin, cloxacillin. 3. Extended spectrum penicillins. Aminopenicillins – ampicillin, amoxycillin Carboxypenicillins – carbenicillin, ticarcillin Ureidopenicillins – piperacillin, mezlocillin β -lactamase inhibitors – Clavulanic acid and sulbactam prevent inactivation by penicillinases produced by various organisms. Spectrum of activity is against gram positive cocci (non penicillinase-producing strains of Staph. aureus, Staph. epidermidis, Streptococci except group D or enterococci), gram negative cocci (Neisseria gonorrheae, Neisseria meningitides), gram positive bacilli (B. anthracis, C. diptheriae, Cl. tetani, Listeria), and spirochetes (Treponema pallidum). Majority of gram negative bacilli are totally insensitive to penicillin. Penicillin G is rapidly degraded by gastric acid (so preferred for IV administration). Penicillin V is preferred for oral administration. Benzathine and procaine penicillins are used for slow release (IM administration). Excretion mainly occurs via tubular secretion (dose adjustment in renal insufficiency).

Dosage • Sodium penicillin G (crystalline penicillin): 0.5-5 MU IM/IV 6-12 hourly. • Procaine penicillin G: 0.5-1 MU IM 12-24 hourly. • Benzathine penicillin G: 0.6-2.4 MU IM every 2-4 weeks. Indications • Syphilis. • Streptococcal infections. • Tetanus. • Gas gangrene. Adverse Effects/ Precautions • Hypersensitivity reactions ranging from mild rash/fever/eosinophilia to fatal anaphylaxis. • Jarisch-Herxheimer reaction – occurs within 2-12 hours of the first dose when using penicillin for syphilis; presents as headache, fever, chills, sweating, sore throat, myalgia/ arthralgia, tachycardia and increased blood pressure. The condition does not recur and does not need interruption of treatment. Aspirin and sedation offer symptomatic relief. • Pregnancy: category B. Drug Interactions • Probenecid – inteferes with tubular secretion of penicillin. AMPICILLIN Pharmacology • β-lactam antibiotic, aminopenicillin group. • Interferes with bacterial cell wall synthesis. • Greater activity than natural penicillins against enterococci and H.influenzae. • Maximal absorption when taken on empty stomach. • Primarily excreted in urine (dose adjustment in renal insufficiency).

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Dosage Oral • Adults and children >20 kg – 250-500 mg Q6h. • Children 1 year) Indications • Acne vulgaris. • Primary, secondary or latent syphilis in nonpregnant patients with documented penicillin allergy. Adverse Effects/ Precautions • GIT - nausea, vomiting, diarrhea, abdominal pain, epigastric burning, anorexia. • Maculopapular or erythematous rashes. • Hypersensitivity reactions. • Hemolytic anemia, thrombocytopenia, neutropenia and eosinophilia. • Photosensitivity. • Precipitation of renal failure in patients with underlying renal function. • Discoloration of teeth (in children < 8 years, or infants of pregnant mothers who ingested tetracycline).

• Superinfection with Candida (oral and anogenital). • Use of discarded or outdated tetracycline has resulted in an adverse event similar to Fanconi’s syndrome (patients should be instructed to discard any unused tetracycline after therapy). • Pregnancy: category D.

Drug Interactions • Absorption of tetracycline is impaired by dairy products, flouroquinolones, sucralfate, or any product containing iron, zinc, calcium, aluminium, magnesium or bismuth (separate administration by 4 hours). • OCPs – decreased efficacy of OCPs. • Warfarin – elevated PT. DOXYCYCLINE Pharmacology • Inhibits protein synthesis by binding to the 30S ribosomal subunit, thereby preventing attachment of the aminoacyl t-RNA to the A site of the mRNA-ribosome complex; primarily bacteriostatic. • In acne – inhibits growth of propionibacterium acnes and decreases free fatty acid concentration in sebum, resulting in decreased inflammation and microcomedo formation. • Spectrum of activity. – Cocci: all gram positive and gram negative cocci were originally sensitive but now many Strep. pyogenes, Strep. pneumoniae, Staph. aureus and enterococci have become resistant – Gram positive bacilli: Clostridia, Listeria, Corynebacteria, Propionibacterium acnes, Bacillus anthracis – Gram negative bacilli: H.ducreyi, Calymmatobacterium granulomatis, Vibrio cholerae, Yersinia pestis, Yersinia enterocolitica, Campylobacter, H. pylori, Brucella, Pasturella, Francisella

Topical Formulary and Key Systemic Drugs – Spirochetes: Treponema pallidum, Borrelia – Rickettsiae – Chlamydia – Mycoplasma, Ureaplasma • Maximum absorption on empty stomach (food may decrease absorption by up to 20%); should be taken with adequate fluids to reduce esophageal irritation/ulceration; can be given with food if gastric irritation occurs. • Equally excreted in feces and urine (unlike other tetracyclines); dose adjustment not needed in renal insufficiency.

Dosage • 100 mg twice a day. Indications Acne vulgaris 1st choice treatment in: – Lymphogranuloma venereum – Granuloma inguinale – Typhus, Rocky mountain spotted fever, Q fever (Rickettsiae) 2nd choice treatment in: – Tetanus, anthrax, actinomycosis, Listeria (to penicillin/ampicillin) – Gonorrhea (to ciprofloxacin/ceftriaxone, especially for penicillin-resistant, nonPPNG organisms and in penicillin allergic cases) – Chlamydial infections – non-gonococcal urethritis, endocervicitis, conjunctivitis, pneumonia (to azithromycin) – Chancroid (to cotrimoxazole)

Adverse Effects/Precautions • GIT- nausea, vomiting, diarrhea, abdominal pain, epigastric burning, anorexia. • Pseudotumor cerebri (increased risk when combined with isotretinoin).

• Photosensitivity. • Discoloration of teeth (in children < 8 years and infants of pregnant women taking the drug). • Superinfection with Candida (oral/ anogenital), pseudomembranous enterocolitis. • Pregnancy: category D.

Drug Interactions • Absorption of doxycycline is impaired by dairy products, flouroquinolones, sucralfate, or any product containing iron, zinc, calcium, aluminium, magnesium or bismuth (separate administration by 1-2 hours). • OCPs – decreased efficacy of OCPs. • Warfarin – elevated PT. MINOCYCLINE Pharmacology • Inhibits protein synthesis by binding to the 30S ribosomal subunit, thereby preventing attachment of the aminoacyl t-RNA to the A site of the mRNA-ribosome complex; primarily bacteriostatic. • In acne – inhibits growth of Propionibacterium acnes and decreases free fatty acid concentration in sebum, resulting in decreased inflammation and microcomedo formation. • Good activity against rickettsia, chlamydia, mycoplasma. • Also displays activity against Staph. aureus resistant to other tetracyclines. • Maximum absorption on empty stomach (food may decrease absorption by up to 20%); should be taken with adequate fluids to reduce esophageal irritation/ulceration; can be given with food if gastric irritation occurs. • Eliminated primarily via the hepatobiliary system.

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Dosage • Acne vulgaris: 50 mg OD – TID. • Infections due to susceptible organisms: 200 mg initial dose (orally or IV), followed by 100 mg Q12h. Indications • Moderate to severe inflammatory acne vulgaris. • Can be used to treat rickettsial, chlamydial, mycoplasmal infections (although doxycycline is the preferred drug). Adverse Effects/ Precautions • GIT – nausea, vomiting, diarrhea, abdominal pain, epigastric burning, anorexia. • Vestibular side effects – dizziness, ataxia, vertigo (dose-related, more common in women). • SLE – rare, reversible. • Pseudotumor cerebri (increased risk when combined with isotretinoin). • Reversible skin and mucous membrane pigmentation occurs with long-term use • Photosensitivity – may be less than other tetracyclines. • Discoloration of teeth (in children < 8 years and infants of pregnant women taking the drug). • Superinfection with Candida (oral and anogenital) less frequent than tetracycline and doxycycline. • Pregnancy: category D. Drug Interactions • Absorption of minocycline is impaired by sucralfate, or any product containing iron, zinc, calcium, aluminium, magnesium or bismuth (separate administration by 1-2 hours). • OCPs – decreased efficacy of OCPs. • Warfarin – elevated PT.

CIPROFLOXACIN Pharmacology • Fluoroquinolone antibiotic; inhibits bacterial DNA gyrase. • Most reliable for treatment of aerobic gram negative organisms. – Enterobacteriaceae – Neisseria gonorrheae, Neisseria meningitides – H. influenzae, H. ducreyi – Campylobacter jejuni – Yersinia enterocolitica • Moderately susceptible organisms include some streptococci, staphylococci, Pseudomonas aeruginosa, chlamydia, and mycobacteria. • Well absorbed after oral administration. • Widely distributed throughout the body; high tissue penetrability (except CSF). • Eliminated primarily via the kidney (dose adjustment needed in renal insufficiency).

Dosage 250-750 mg BD, depending on the indication.

Indications • • • •

Skin and skin structure infections. Gonorrhea. Bone and joint infections. Urinary tract infections (cystitis, pyelonephritis). • Intra-abdominal infections, diarrhea (in combination with metronidazole). • Typhoid. • Sinusitis, lower respiratory tract infections.

Adverse Effects/ Precautions • GIT – nausea, vomiting, bad taste, anorexia. • CNS – dizziness, headache, restlessness, anxiety, insomnia, impairment of concentration and dexterity (caution while driving), tremor, seizures.

Topical Formulary and Key Systemic Drugs • Hypersensitivity reactions – rash, pruritus, photosensitivity, urticaria, swelling of lips, fever, hepatic necrosis, fatal anaphylaxis. • Tendonitis and tendon rupture. • Cartilage damage in weight bearing joints (in animal studies) – not recommended for children. • Pregnancy: category C.

• Not effective against Pseudomonas, enterococci, and most anaerobes • Increased resistance being seen with H. influenzae, E. coli, staphylococci and streptococci • Well absorbed orally. • Excreted primarily in urine (dose adjustment needed in renal insufficiency).

Drug Interactions • Products containing multivalent cations such as iron, calcium, zinc, magnesium, aluminium (e.g. antacids, multivitamins, sucralfate) impair the absorption of ciprofloxacin – should be administered 6 hours before or 2 hours after ciprofloxacin. • Theophylline – ciprofloxacin can increase theophylline concentrations. • Warfarin – increased PT.

Dosage • All preparations contain TMP and SMX in the ratio of 1:5. • Oral – one double strength TMP/SMX (160/ 800 mg) tablet BD. • Intravenous – 8-20 mg/kg/day of TMP in 2-4 divided doses.

TRIMETHOPRIMSULPHAMETHOXAZOLE (SEPTRAN) Pharmacology • Trimethoprim is a diaminopyrimidine related to the antimalarial drug pyrimethamine, which selectively inhibits bacterial dihydrofolate reductase (DHFRase). • Sulphamethoxazole belongs to the class of sulfonamides, which are structural analogues of PABA, and thereby inhibit bacterial folate synthetase. • The combination (TMP-SMX) results in a synergistic bactericidal effect on gram positive and gram negative organisms – Strep. pneumoniae – Strep. pyogenes – Staph. aureus – H. influenzae – Moraxella catarrhalis – Nocardia species – Stenotrophomonas maltophila – Enterobacteriaceae (most) – Pneumocystis jiroveci

Indications • Chancroid (1st choice agent). • Granuloma inguinale (2nd choice agent). • Toxoplasmosis. • Nocardia infections. • Urinary tract infections – treatment and prophylaxis. • Respiratory tract infections (acute otitis media, acute exacerbations of chronic bronchitis, sinusitis). • Diarrhea and dysentery. • PCP pneumonia. Adverse Effects/ Precautions • GIT – nausea, vomiting, anorexia. • Hypersensitivity – rash, urticaria, StevensJohnson syndrome, TEN, erythema multiforme and exfoliative dermatitis. • Agranulocytosis, aplastic or hemolytic anemia (folate deficient patients at increased risk). • Fulminant hepatic necrosis. • HIV infected patients are at much greater risk of dermatologic and hematologic reactions, and desensitization may be required. • Crystalluria (advised to drink plenty of water). • Pregnancy: category C.

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Drug Interactions • Warfarin – antithrombotic effects can be potentiated by TMP/SMX. • Sulfonylureas – hypoglycemia as a result of displacement from protein binding sites. • Methotrexate – displacement from protein binding sites, and competition for renal tubular excretion, leading to bone marrow suppression. CORTICOSTEROIDS The corticosteroids bind to specific cytoplasmic receptors in the target cell and the steroid receptor complex then undergoes modification and is translocated to the nucleus where it causes formation of specific mRNA which then mediates the various biological effects. Their modes of actions are 1) Anti-inflammatory, 2) Antiallergic and 3) Immunosuppressive.

Dosage The intermediate acting steroid namely prednisolone is commonly used at a dose of 1 mg/kg body weight/day. Indications 1. Autoimmune bullous dermatoses (pemphigus, bullous pemphigoid, epidermolysis bullosa acquisita, etc.). 2. Drug eruptions (erythema multiforme, Stevens Johnson syndrome, TEN). 3. Connective tissue disorders (SLE, polymyositis, dermatomyositis, progressive systemic sclerosis). 4. Severe dermatitis (atopic dermatitis, contact dermatitis, photodermatoses). 5. Neutrophilic dermatoses (pyoderma gangrenosum, Sweet’s syndrome). 6. Sarcoidosis. 7. Leprosy in severe reaction. 8. Urticaria, angioedema and capillary hemangiomas.

Contraindications There are no absolute contraindications The relative contraindications are: Peptic ulcer disease, any focus of infection including tuberculosis, hypertension, glaucoma, cataract, hyperlipidemia, renal calculi, first trimester of pregnancy, and children. Side Effects 1. Metabolic disturbances: Diabetes, faciotruncal obesity, hyperlipidemia, protein hypercatabolism, etc. 2. Bone disturbances: Osteoporosis, avascular necrosis of the bone, growth retardation. 3. Muscular disorders: Steroid myopathy, amyotrophy, tendon rupture. 4. Cutaneous effects: Acneiform eruptions, atrophy, telangiectasia, easy bruising, alopecia/hypertrichosis, cutaneous infection, striae distense. 5. Electrolyte disturbances: Sodium retention and potassium depletion. 6. Endocrine changes: Inhibition of the hypothalamo-hypophyseal suprarenal axis. 7. Infections: Acute bacterial infection, tuberculosis, viral infection, parasitic disease. 8. Neuropsychiatric disorders: Neuropathy, psychosis, pseudotumor cerebri. 9. Ocular effects: Posterior subcapsular cataract, open angle glaucoma, aggravation of an existing infection. 10. Gastric disturbances: Peptic ulcer disease. 11. Hematologic alteration: Leucocytosis, eosinopenia and lymphopenia. GRISEOFULVIN Griseofulvin is the most frequently used systemic drug in the treatment of dermatophytosis. It is a fungistatic agent derived from Penicillium griseofulvum with selective activity against dermatophytes only. In addition to its antifungal

Topical Formulary and Key Systemic Drugs activity, it is also a weak vasodilator and inhibits leucocyte chemotaxis.

herpes zoster, the dose is 800 mg orally 5 times a day for 7 to 10 days.

Dosage The daily recommended dose is 10-20 mg/kg body weight/day to a maximum of 1 gm daily, given in a single dose or in two divided doses. For ringworm of the trunk, hand or foot, it is given for a period of 4 to 6 weeks. For scalp infection 8 to 12 weeks and in nail infection for 12 to 18 months.

Side Effects

Side Effects The most commonly reported adverse effects are headache and gastrointestinal side effects namely dyspepsia, nausea and diarrhoea. Other side effects are photosensitivity, urticaria, erythema multiforme, maculopapular skin rash, serum sickness, angioedema and vesicular eruption. The other uncommon but serious adverse effects include hepatic and renal insufficiency, severe leukopenia, peripheral neuropathy, mental confusion and blurred vision. It can also precipitate SLE. ACYCLOVIR Acyclovir is a synthetic guanosine analogue which is widely used for the treatment of herpes simplex virus and varicella zoster virus infections. Acyclovir, a prodrug, initially undergoes monophosphorylation by herpes virus encoded thymidine kinase and is activated to acyclovir triphosphate (by cellular kinase) which is the active antiviral moiety. Acyclovir is highly selective because only virus infected cells are able to phosphorylate acyclovir.

Dosage The recommended dose for the treatment of HSV infection is 200 mg 5 times a day or 400 mg three times a day for 7 to 10 days. For varicella and

They are renal crystalluria, interstitial nephritis, seizures, tremors, etc.

ANTIHISTAMINES Classification Class I: First generation H1 type antihistamines – These traditional antihistamines are competitive receptor blockers (reversible) and can be displaced by high levels of histamines and they dissociate from the receptors easily. They are divided into 6 groups. 1. Alkylamine – Pheniramine maleate (25-50 mg 2-3 times daily) – Chlorpheniramine maleate (4 mg thrice daily) 2. Ethanolamine – Clemastine fumarate (1 mg twice daily) – Embramine hydrochloride (25-50 mg/ day) – Bromodiphenyl hydramine hydrochloride – Diphenhydramine hydrochloride(25-50 mg thrice daily), citrate 3. Ethylenediamine – Mepyramine maleate – Pyrilamine maleate – Tripelamine citrate, HCl 4. Phenothiazine – Promethazine HCl (25 mg twice daily) – Methdilazine HCl 5. Piperidine – Cyproheptadine HCl (4 mg thrice daily) – Azatidine maleate 6. Piperazine – Hydroxyzine hydrochloride (10 mg or 25 mg thrice daily).

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Essentials in Dermatology Mechanisms of action: The main effects are as follows: 1. Anticholinergic activity 2. Anti-inflammatory effect 3. Antiallergic effect 4. Antimotion sickness effects 5. Antiemetic activity 6. Inhibit most responses of smooth muscle to histamine.

Indications

Side Effects 1. Neurological side effects – Sedation, dizziness and tinnitus, blurred vision and diplopia, insomnia, reduced or disturbed concentration, irritability and tremors. 2. Gastrointestinal side effects – Anorexia, nausea, vomiting, epigastric distress, constipation (can be minimized by giving them along with food). 3. Anticholinergic effects – dry mucous membranes, difficulty in micturition and urinary retention, frequency and dysuria, impotence. 4. Cutaneous side effects –eczematous dermatitis, fixed drug eruption, photosensitivity, urticaria, petechiae.

3. Mast cell disorders: Ketotifen, cimetidine, azelastine and chlorpheniramine are very effective.

Class II: Second generation H1 antihistamines. They are non-competitive blockers and dissociate slowly from the receptors and have a longer duration of action. They are devoid of sedative and anticholinergic effects. These drugs are: acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratidine, mizolastine, terfenadine. The drugs commonly used are cetirizine (10 mg/day), loratidine (10 mg/day), terfenadine (60 mg BD) and astemizole (10 mg/day), with a loading dose of 10 mg tds x 3 days). Class III: H 2 antihistamines – Cimetidine, ranitidine, famotidine, nizatidine. Class IV: Other drugs with antihistamine activity – Tricyclic antidepressants (doxepin), ketotifen, oxafomide.

1. Urticaria and angioedema: Both traditional and second generation antihistamines are found to be useful. The combination of both H1 and H2 antihistamines are very effective in the treatment of acute or chronic idiopathic urticaria and physical urticarias. 2. Pruritus of various causes: viz. dermatitis, papulosquamous disorders, insect bites, etc.

4. Pruritus due to: Myelofibrosis, polycythemia vera and carcinoid flush. Cimetidine is also effective. 5. The immunomodulatory effects of H 2 antihistamines may offer great therapeutic potential. 6. Other uses include, their use in motion sickness, vertigo, preanesthetic medication, as sedative, hypnotic and anxiolytic.

DAPSONE Dapsone is a 4,4’-Diaminodiphenyl sulphone. It is weakly bactericidal against M.leprae. It acts by inhibiting folate metabolism in M.leprae. In addition to its antibacterial action, it also has antiinflammatory activity–inhibits lysosomal enzymes, interferes with myeloperoxidase system. During daily treatment with 100 mg dapsone, it inhibits the generation of 5-lipoxygenase product in neutrophils.

Dosage Dose is 6 to 10 mg/kg body weight/week. The average adult dosage is 100 mg/day. For children of 10 to 14 years, it is 50 mg/day and of 6 to 9 years it is 25 mg/day. Indications Other than its antileprosy action, it is used in dermatology in pemphigus, bullous pemphigoid,

Topical Formulary and Key Systemic Drugs dermatitis herpetiformis, subcorneal pustular dermatosis, acne conglobata, systemic lupus erythematosus, vasculitis, lichen planus etc.

Side Effects 1. Hemolytic anemia especially in G6PD deficient individuals. 2. Agranulocytosis. 3. Hepatitis. 4. Allergic rashes including FDE and exfoliative dermatitis. 5. Dapsone syndrome (fever, jaundice, lymphadenopathy, hepatomegaly and exfoliative dermatitis). 6. Psychosis. CLOFAZIMINE Clofazimine is a riminophenazine dye. Like dapsone, it is also weakly bactericidal against M.leprae and virtually nontoxic in the usual dosage used. Clofazimine has both antibacterial and anti-inflammatory activities.

Indications Apart from its use in multidrug therapy in leprosy, it is used in dermatology for multidrug resistant tuberculosis, atypical mycobacterial infection, neutrophilic dermatoses (acne, pustular psoriasis), rhinoscleroma, leishmaniasis, etc.

Dosage The recommended dose is 50 mg daily.

Side Effects 1. Reversible dose related reddish to brownish black discoloration of sweat, hair, sputum, urine and feces. 2. Ichthyosis. 3. Phototoxicity, nonspecific skin rashes and acneiform eruptions.

4. Eosinophilic enteropathy. 5. Conjunctival pigmentation.

METHOTREXATE Methotrexate (MTX) is a folic acid antagonist and is widely used for the treatment of severe psoriasis.

Dosage 1. Weekly single oral or parenteral dosage schedule. 2. Intermittent oral schedule of three divided doses 12th hourly over a period of 36 hours each week. 3. Oral dose is 0.4 to 0.6 mg/kg body weight/ week (maximum 30 mg). 4. Parenteral dose is 15-25 mg/week. Indications 1. Psoriasis – psoriatic erythroderma, psoriatic arthritis, pustular psoriasis, extensive psoriasis vulgaris. 2. Reiter’s syndrome and pityriasis rubra pilaris. 3. Sarcoidosis. 4. Polymyositis and systemic lupus erythematosus. 5. Pemphigus vulgaris and other bullous disorders. Side Effects 1. Gastrointestinal – nausea, vomiting, stomatitis, diarrhoea, ulceration, etc. 2. Hepatitic – abnormal liver enzymes, hepatic, fibrosis and cirrhosis. 3. Hematopoietic – anemia, thrombocytopenia, leucopenia, pancytopenia. 4. Pulmonary – acute hypersensitivity, fibrosis, pneumonia. Most common side effect is nausea and vomiting. Serious late side effect is cirrhosis of the liver.

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PSORALENS Of the many psoralens isolated and synthesized, three are in routine clinical use. These include 8 methoxypsoralen (8-MOP), 5 methoxypsoralen (5-MOP) and trimethyl psoralen (TMP). They are active only when combined with UVA irradiation. It interferes with DNA synthesis and blocks epidermal cell proliferation, has immunomodulatory effects and immunosuppressive effects along with induction of epidermal thickening and melanogenesis.

Dosage Oral 8-MOP is given in a dose of 0.6 to 0.8 mg/kg body weight/day. Two hours later, the patient is exposed to ultraviolet radiation A (UVA) at a dose of 1 joule/square cm to begin with, which is gradually increased to minimal erythema dose depending on the skin type. Therapy is usually given two to three times per week. The number of exposures required for achieving control are usually between 15 and 25. Maintenance therapy involves less frequent treatments often as little as once every two to four weeks, with eventual discontinuation of treatment. Indications 1. Psoriasis. 2. Vitiligo. 3. Photodermatoses. 4. Cutaneous T-cell lymphomas. Side Effects 1. Nausea, vomiting. 2. Cutaneous – Acute sunburn and erythema, irreversible hyperpigmentation of the skin, PUVA lentigines, actinic keratoses, premature ageing of the skin. 3. Ocular – cataract. It can be prevented by using sunglasses on the day of treatment. 4. Carcinogenesis.

Other than oral PUVA therapy, psoralen may be used for topical PUVA therapy and bath PUVA therapy.

RETINOIDS Retinoids is a generic term that includes both naturally occurring molecules and also synthetic compounds showing specific biological activities resembling those of vitamin A(retinol). Synthetic retinoids are produced by chemical modification of vitamin A. Three generations are known today(nonaromatic, monoaromatic, and polyaromatic). First generation(Nonaromatic) includes retinal and compounds that can be derived from it metabolically e.g. retinyl palmitate(topical), retinyl aldehyde(topical), tretinoin(all trans retinoic acid)(topical), 9-cis-retinoic acid, a-14hydroxyretroretinol, fenretinide(N-[4-hydroxyphenyl]-retinamide), E 5166(polyprenoic acid). Second generation(Monoaromatic) by addition of an aromatic ring e.g. etretinate, isotretinoin, acitretin, isoacitretin(13-cis-acitretin), motretinide. Third generation(Arotinoids) e.g. temarotene, arotenoid acid, arotenoid ethyl ester, arotenoid ethyl sulphone, arotenoid methyl sulphone, adapalene(topical antiacne agent), tazarotene (topical antipsoriatic agent). Intracellularly retinoids interact with cytosolic proteins and then enter the nucleus. By changing the expression of growth factors, oncogenes, keratin or transglutaminases, retinoids could exert wide spread changes in growth and differentiation.

Indications of Systemic Retinoids 1. Psoriasis and related disorders. 2. Other disorders of keratinization. 3. Seborrhoea, acne and acneiform dermatoses. 4. Rosacea and other acne related dermatoses.

Topical Formulary and Key Systemic Drugs 5. Cancers-basal cell carcinoma, actinic keratosis, cutaneous T-cell lymphomas, HIV related Kaposi’s sarcoma. 6. Other dermatoses such as lichen planus, lupus erythematosus, lichen sclerosus et atrophicus, prurigo nodularis, photoageing and ageing, pigmentary disorders, etc.

Side Effects of Systemic Retinoids The adverse effect profile closely resembles those of hypervitaminosis A. Acute toxicity is dose dependent and reversible. 1. Cheilitis appears 2-3 weeks after initiation of therapy in 100% of patients and is regarded as a marker of sufficient absorption. Other mucocutaneous adverse effects are skin and

mucosal dryness, skin fragility and/or stickiness, retinoid dermatitis, palmoplantar desquamation, pruritus, hair loss, paronychia, and photosensitivity. 2. Eye symptomatology and pseudotumor cerebri. 3. Serum lipids and liver function abnormalities. Chronic Toxicity 1. Bone changes include hyperostosis, periostosis, osteoporosis, thinning of the bones, premature closure of epiphyses, DISH(diffuse idiopathic skeletal hyperostosis), extraspinal calcification, bone pain and acute arthritis. 2. Arthralgia and myalgias 3. Teratogenicity involving central nervous system, skeletal system, cardiovascular system, and other organs.

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Dermatosurgical Procedures

SKIN BIOPSY Skin biopsy is the commonest investigation performed by any dermatologist. The diseased tissue obtained is subjected to microscopic and/ or other investigations.

Indications 1. Most frequently skin biopsy is taken to confirm a clinical diagnosis or to aid in the establishment of a diagnosis where clinical diagnosis is not apparent. 2. Sometimes, biopsy is excisional for the treatment of skin lesions particularly malignant neoplasms and other lesions for cosmetic reasons. 3. Skin biopsy may be used for a variety of investigative procedures such as ultrastructural examination, immunofluorescence studies, enzyme histochemistry and immunohistochemistry, microbiological studies, tissue culture, etc. Site of biopsy: Ideally, the lesion biopsied should be an early and untreated lesion and representative of the skin disorder as a whole. If lesions are present at all stages of evolution, it may be appropriate to biopsy more than one lesion. Normal skin should be included with a diagnostic biopsy wherever possible.

Written consent is normally obtained from the patient and local anesthesia with 1% or 2% lignocaine with or without adrenaline is injected around the biopsy site. Techniques of skin biopsy: Elliptical surgical biopsy, punch biopsy, curettage or shave biopsy may be undertaken. Elliptical surgical biopsy: A reasonable size for an elliptical biopsy is about 12 x 5 mm. It is undertaken with a scalpel and the wound is sutured. Punch biopsy: The biopsy punch of at least 5 mm is required to obtain satisfactory specimen. The punch is pushed into the skin with a downward twisting movement and then removed. The tissue specimen is lifted and cut. The wound may be left to heal without suturing. The biopsy specimen is put in 10% formalin solution for histopathologic studies. It is properly labeled and sent to pathology department with full clinical details of the case.

ELECTROSURGICAL PROCEDURES IN DERMATOLOGY Electrical current of sufficiently high frequency not to stimulate nerves or muscles can pass through tissue with little effect other than the

Dermatosurgical Procedures production of heat. Heat is produced from the electrical resistance of the tissue as current travels from one electrode to the other. When the electrodes are both large (as in medical diathermy), the heat is dispersed over a large area, and no injury ensues. However, if the emitting electrode is reduced to a small tip, the heat produced at the point of contact is sufficiently intense to cause localized tissue injury. As might be anticipated, variation in the voltage, amperage, frequency, and method of application gives each of the electrosurgical modality its unique qualities. Equally important, however, is the waveform of each current. In practice, a spark-gap apparatus produces damped waves, whereas a vacuum tube or transistorized unit creates continuous waves. Examples of the former include the Hyfrecator (Birtcher Corp., El Monte, CA) commonly employed in dermatology.

Electrodesiccation and Electrofulguration The difference between electrodesiccation and electrofulguration lies in the placement of the elec-trode tip. In electrodesiccation (Lat. Siccus ‘dry’), the tip contacts the skin and causes a radial spread of current . In electrofulguration [Lat. fulgur ‘lightning’] the tip remains above the skin and the charge leaps to the surface in a diffuse, or “defocused,” pattern , causing flatter and more superficial tissue destruction. The histologic outcome of both modalities is one of tissue desiccation. As a result of the low heat production, electrodesiccation and electrofulguration are best suited for superficial and comparatively avascular lesions such as verrucae and seborrheic keratoses. Electrocoagulation Electrocoagulation [Lat. Coagulum ‘clot’ or ‘curd’] is produced by a high-frequency

alternating current of high amperage (2,5004,000 mA) and low voltage (101o F Abnormal cervical or vaginal discharge WBCs on saline mount of vaginal discharge Elevated ESR and C-reactive protein Laboratory documentation of cervical infection with N.gonorrheae or C. trachomatis.

Specific Criteria (required only in Certain Cases) • Endometrial biopsy showing endometritis • Transvaginal sonography or MRI scan showing tubal abnormalities or tubo-ovarian abscess. • Laparoscopic findings of PID.

Treatment • Treatment should be initiated with minimal criteria and needs to cover all the etiological pathogens. Early treatment prevents sequelae. • Parenteral therapy is given for the initial 24 – 48 hours and thereafter oral therapy is continued.

Bacterial vaginosis (Leukorrhea; Haemophilus vaginalis vaginitis; Gardnerella vaginalis vaginitis; Anaerobic vaginosis; Vaginal bacteriosis) • Bacterial vaginosis (BV) is a common cause of abnormal vaginal discharge in women of reproductive age. • It represents a complex change in vaginal flora characterized by a reduction in the prevalence and concentration of hydrogen peroxide producing lactobacilli and increase in the prevalence and concentration of Gardnerella vaginalis; Mobiluncus species; Mycoplasma hominis; anaerobic gram-negative rods belonging to the genera Prevotella, Porphyromonas, and Bacteroides; and Peptostreptococcus species. • Amsel et al has proposed a set of practical diagnostic criteria for the clinical diagnosis of BV that is now often accepted as the “gold standard.” Diagnosis requires three or more of the following clinical/diagnostic features: 1. The presence of (excessive) homogeneous vaginal discharge 2. Elevated vaginal pH >4.5 3. Positive amine test (Whiff test) 4. 20% “clue cells” (vaginal epithelial cells adhered to by infective microbes) and typical Gram stain appearance upon microscopy of vaginal secretions including absence of lactobacilli (Fig. 31.22).

Regimens include – IV Cefoxitin plus oral doxycycline (after 24 hours IV drugs stopped and oral doxycycline continued) or IV clindamycin and gentamicin (24 hours) followed by oral doxycycline or IV ofloxacin with metronidazole or IV ampicillin plus doxycycline • Male sexual contacts (in the preceding 60 days) should be treated.

Fig. 31.22: Gram’s stained vaginal discharge smear showing a normal vaginal epithelial cell and another coated with bacteria

Sexually Transmitted Diseases

Treatment • All women who have symptomatic BV disease require treatment. • Metronidazole 500 mg orally twice a day for 7 days, or Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days, or Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days are recommended treatments. • Alternatively, patient may be treated with Metronidazole 2 g orally in a single dose, Clindamycin 300 mg orally twice a day for 7 days, or Clindamycin ovules 100 g intravaginally once at bedtime for 3 days. Differential diagnoses of vaginal discharge Profile

Normal vaginal discharge

Candidal vulvovaginitis

Trichomonal vaginitis

Bacterial vaginosis

Etiology

Lactobacillus predominant

Candida spp. and other yeasts

Trichomonas vaginalis

Associated with G.vaginalis; anaerobic bacteria, and Mycoplasma hominis

Symptoms

None

Vulvar pruritus and/ or irritation; external dysuria, increased vaginal discharge

Profuse discharge, often malodorous; external dysuria and genital irritation often present

Malodorous, increased discharge (commonly present at the introitus)

Amount

Variable; usually Scant to moderate scant Clear or white White

Profuse

Moderate to profuse

White, yellow or green

White or gray

Nonhomogenous, Clumped, “Cheesy” flocculant adherent exudative plaques

Homogeneous, watery, often frothy

Homogeneous, uniformly coating vaginal walls

Color Consistency

pH

Usually 4.5

Amine odor with 10% KOH

None

None

Usually present

Present

Associated inflammatory signs

None

Erythema, edema and / or erosions of vagina or external genitalia; vulvar dermatitis common

Erythema of vaginal mucosa, introitus; occasional cervical petechiae; vulvar dermatitis

None

Microscopy of discharge

Normal epithelial cells; lactobacilli predominate

Leukocytes, epithelial cells; yeast, mycelia, pseudomycelia seen

Leukocytes; motile trichomonads seen

Clue cells; rare leukocytes; lactobacilli outnumbered by mixed flora

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MISCELLANEOUS STDs Anogenital Warts • The etiologic agent of anogenital warts or condyloma acuminata is the human papilloma virus (HPV) a non-enveloped, double standard DNA virus. • More than 80 different genotypes of HPV have been identified. Forty-five of these are known to affect the genital epithelium and are considered to be sexually transmitted infections. • It is roughly estimated that up to 30% to 50% of sexually active adults are infected with HPV. The highest rates of infection are found in women, 19-22 years of age and in men, 2226 years of age. • HPV 6 and 11 are most commonly associated with genital warts, but at least 20 different HPV genotypes have been associated with condyloma acuminata. • The infectivity of HPV between sexual partners is estimated to be 60%. • The most common locations of primary infection include the fourchette in women and

Fig. 31.23

•

•

•

•

•

the subpreputial region in men. Men have been found to be at increased risk if they fail to wear a condom and if they are smokers. Most genital warts occur on the penis, scrotum, urethral meatus, and perianal area in men. The clinical types of anogenital warts are Condyloma acuminata (acuminate warts) (Figs 31.23 and 31.24), papular warts, verruca vulgaris type or keratotic warts, sessile warts, flat warts, intraepithelial neoplasiaBowenoid papulosis and Bowen’s Disease, and “Giant condyloma” (Buschke – Lowenstein tumor) Subclinical HPV infection is one that is not clinically visible with the unaided eye, requiring colposcopy with or without acetowhitening or histopathology. Latent HPV infection means the presence of HPV can be confirmed only by the detection of the HPV DNA Atypical lesions occur in immunocompromized patients such as HIV infected individuals

Fig. 31.24

Figs 31.23 and 31.24: Condyloma acuminata—genital outgrowths

Sexually Transmitted Diseases Diagnosis • Diagnosis is typically made on clinical basis. • The most sensitive method for detection of HPV DNA is polymerase chain reaction. • Acetowhitening is a diagnostic tool. • But the most commonly utilized and widely available method is histopathologic examination of a tissue biopsy.

Differential Diagnosis Morphologically, various conditions, which need to be differentiated from verrucous lesions of genital warts, are condyloma lata of syphilis, nonvenereal treponematosis, hypertrophic verrucous type of granuloma inguinale, tuberculosis verrucosa cutis, skin tags, and malignancy. For small genital warts, various differential diagnoses need to be considered are pearly penile papules (Fig. 31.25), vestibular papillomatosis, molluscum contagiosum, seborrhoeic keratosis, Fordyce’s spots, urethral caruncle, lichen planus, and foreign body granuloma. For subclinical infection (seldom appears reddish), candidial infection of the vulva and repeated topical application of antifungals need to be ruled out. Other benign tumors like neurofibroma, lipoma, fibroepitheliomata, and normal physiological glands like Tyson’s glands also need to be considered before appropriate diagnosis is made. Around the anus, prolapse and sentinel piles, and anal tags

Fig. 31.25: Pearly penile papules often misdiagnosed as genital warts

may be confused with anogenital warts. In unhygienic persons, dry smegma may appear like warts and hence cleaning the sub-preputial region is emphasized before the examination of warts in male genitalia. For the pathological specimen of genital warts, various differential diagnoses considered are seborrheic keratosis, molluscum contagiosum, psoriasis, lichen planus, condylomata lata, Bowen’s disease and squamous cell carcinoma.

Treatment Treatment options may be categorized into cytodestructive methods (surgical excision, cryotherapy, laser therapy, bichloroacetic acid / trichloroacetic acid, podophyllin and podophyllotoxin), antimetabolic therapy (5-fluorouracil), antiviral therapy (cidofovir and interferons [IFNs]) and immunomodulation (imiquimod) 1. Podophyllin 10-25% (applied to the warts using cotton tipped swab once or twice a week for up to six weeks) or podophyllotoxin 0.5% (the solution or cream is applied with cotton swab or finger respectively, over the condylomas also on normal appearing skin between the lesions twice daily for three days followed by four days of no therapy) for local use is first line therapy. 2. Imiquimod cream, supplied in single use sachets, is applied to the warts with fingers three times per week (every other night) and the area washed with mild soap and water the next morning. Treatment continued until wart clearance, or for a maximum of 16 weeks 3. Cryotherapy – treatment of choice for condyloma acuminata in pregnancy. 4. CO2 laser 5. Surgery 6. Interferons (as adjuvant to surgery), 5-fluorouracil (urethral warts), cidofovir, or retinoids are other treatment options 7. Since treatment is often unsatisfactory and is not directed at elimination of the virus, some

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Essentials in Dermatology progress has been made in the development of the HPV vaccines 8. Patient counseling- Advise female patients about regular participation in cervical cytology screening programmes. Use barrier protection with new sexual contacts until successful treatment has been completed

Molluscum Contagiosum • Molluscum contagiosum is a benign papular condition of the skin, which is often sexually transmitted in adults. • Molluscum contagiosum virus is the final remaining member of poxviridae family that specifically infects humans. • The incidence of molluscum contagiosum in sexually active adults has been increasing significantly throughout the past few decades. • Mechanical trauma appears to facilitate the transmission of molluscum contagiosum virus. There is no information about the efficiency of sexual transmission of MCV. • Lesions begin as tiny papules, which grow over several weeks to a diameter of 3 to 5 mm. The flesh coloured papules are smooth, firm and dome shaped with a highly characteristic central umbilication. In adults lesions most commonly occur on the thighs, inguinal region, buttocks and lower abdominal wall (Fig. 31.26). Scabies • Scabies can be sexually transmitted. • When scabies spreads through sexual transmission, the characteristic lesions are more likely to occur on the genitalia, lower abdomen or thigh. • The penis and bra lines are other favourite locations for mite. Pediculosis Pubis • Pediculosis pubis is primarily a sexually transmitted infection occurring predo-

Fig. 31.26: Molluscum contagiosum with herpes genitalis

minantly in the young sexually active population. • Phthirus pubis is the causative organism. • Main symptom is itching which leads to scratching, erythema, irritation and inflammation.

Chronic Viral Hepatitis Sexual activity may profoundly influence the risk for acquisition of both hepatitis A virus (HAV) and hepatitis B virus (HBV) infection. To some extent sexual behavior may also determine the risk of infection with hepatitis C virus (HCV) and HDV. Prevention of STDs • The most reliable way to avoid transmission of STDs is to abstain from sexual intercourse (i.e., oral, vaginal, or anal sex) or to be in a long-term, mutually monogamous relationship with an uninfected partner. • Both partners should get tested for STDs, including HIV, before initiating sexual intercourse. • If a person chooses to have sexual intercourse with a partner whose infection status is unknown or who is infected with HIV or another STD, a new condom should be used for each act of insertive intercourse.

Human Immunodeficiency Virus Infection (HIV) and AIDS

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Human Immunodeficiency Virus Infection (HIV) and Acquired Immunodeficiency Syndrome (AIDS)

HISTORICAL BACKGROUND • AIDS was first recognized and described as a clinical entity in mid 1981 when FriedmanKien and Gottlieb et al described groups of gay (homosexual) men in the USA with Kaposi’s sarcoma and pneumocystis carinii pneumonia (PCP), both previously very rare diseases and known to be linked to immunosuppression. • In June 1983, Barré Sinoussi and Montagnier of the Pasteur Institute in Paris reported the discovery of a new virus isolated from a lymph node of a gay (homosexual) man with persistent lymphadenopathy. They called this new virus lymphadenopathy associated virus (LAV) and postulated that this was the cause of AIDS. • In 1984, Gallo reported the isolation of a new retrovirus that he called human T-cell lymphotropic virus III (HTLV III). Serum antibody testing for this virus was found to be positive in almost 100% of AIDS patients. • In 1987, an international nomenclature committee decided that the new virus should be termed human immunodeficiency virus or HIV rather than HTLV III or LAV. • In 1987, Clavel et al isolated a second retrovirus from AIDS patients in West Africa,

which he termed it as HIV-2. HIV-2 causes AIDS in an identical way to HIV-1 although with a longer disease free period. • The first reported cases of HIV infections diagnosed in India were among Madras commercial sex workers (CSWs) in May 1986. • The epidemic of HIV in India is similar in many ways to the experience in sub-Saharan Africa and Thailand. • The estimated number of HIV infected adult cases (15-49 years) in the country as on 2004 was 5.134 million (based on HIV sentinel surveillance data of National AIDS Control Organization). Causative Organism • Human immunodeficiency virus (HIV) is an RNA retrovirus. It is called retrovirus as it utilizes a DNA polymerase enzyme reverse transcriptase to convert viral RNA to DNA and finally DNA is transcribed to RNA. • It mainly targets CD4+T lymphocytes and thus causes a profound defect in cell mediated immunity leading to opportunistic infections and neoplastic processes.

MODE OF TRANSMISSION • HIV infection is primarily transmitted through sexual route and less commonly through blood transfusion, maternofetal

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Essentials in Dermatology transmission, intravenous drug abuse, needle stick injuries, etc. • In other words, HIV is transmitted through semen and vaginal fluids, infected blood and blood products, infected mother to her babybefore birth, during birth or through breast milk.

SPECTRUM OF HIV INFECTION • Infection with HIV produces a spectrum of disease that progresses from a clinically latent or asymptomatic state to AIDS as a late

manifestation. The pace of disease progression varies. • In untreated patients, the time between infection with HIV and the development of AIDS ranges from a few months to as long as 17 years (median: 10 years). • Most adults and adolescents infected with HIV remain symptom-free for extended periods, but viral replication is active during all stages of infection, increasing substantially as the immune system deteriorates. • In the absence of treatment, AIDS eventually develops in almost all HIV-infected persons.

Clinical Stages of HIV Infection Stage of HIV infection

Clinical features

CD4 count (cells/uL)

Duration (days)

1. Primary HIV infection

Acute seroconversion illness: fever, pharyngitis, fatigue, rash, mucocutaneous ulcers, lymphadenopathy (occipital, axillary, cervical), headache, meningitis, encephalitis, neuropathies

150-800

3-14 days

2. Asymptomatic

Lymphadenopathy, headache

>300

2-10 years or more

3. Early symptomatic

Recurrent varicella zoster, oral candidiasis, oral hairy leukoplakia, seborrheic dermatitis, psoriasis, skin and nail infections (impetigo, folliculitis, fungal intertrigo, paronychia), bacterial infections (pneumonia, bronchitis, sinusitis), unexplained fatigue/fever /sweats/ weight loss, diarrhea, vaginal candidiasis, cervical dysplasia, cervical carcinoma in situ, recurrent pelvic inflammatory disease, tuberculosis

150-500

1-5 years

4. Late symptomatic and advanced

Kaposi’s sarcoma, lymphoma, PCP pneumonia,toxoplasmosis, esophageal candidiasis, cryptococcosis, cryptosporidiosis, recurrent HSV infection, HIV-associated dementia, progressive multifocal leukoencephalopathy, tuberculosis, CMV retinitis, primary CNS lymphoma, Mycobacterium avium intracellulare (MAC) infection

Late symptomatic: 50-200 Advanced: 29%)

A1

B1

C1

200 to 499/mL (14% to 28%)

A2

B2

C2

2 episodes in 12 months) – Salmonella septicemia, recurrent (nontyphoid) – Candidiasis: esophageal, pulmonary – Cryptococcosis: extrapulmonary – Coccidioidomycosis: disseminated/ extrapulmonary – Histoplasmosis: disseminated/ extrapulmonary – Pneumocystis jiroveci (formerly carinii) pneumonia – Herpes simplex virus infection: esophageal, pulmonary, mucocutaneous ulcers of >1 month duration – Cytomegalovirus: other than liver, spleen or nodes

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Human herpesvirus-8 infection: Kaposi’s sarcoma Human papillomavirus infection: invasive cervical cancer Cryptosporidiosis: chronic intestinal (>1 month duration) Isosporiasis: chronic intestinal (>1 month duration) Toxoplasmosis of brain Kaposi’s sarcoma Wasting syndrome due to HIV (involving weight loss >10% of baseline body weight), associated with either chronic diarrhea (> 2 loose stools per day for > 1 month) or chronic weakness and documented fever > 1 month

Note AIDS in HIV-infected adolescents and adults aged >13 years defined by CDC includes any one of the following criteria: (a) 1 month duration.

Minor Signs a. Repeat common infections (e.g. Pneumonitis, otitis, pharyngitis etc.) b. Generalized lymphadenopathy c. Oropharyngeal candidiasis d. Persistent cough for more than 1month e. Disseminated maculo-papular dermatosis II. Case Definition of AIDS in adults (for persons above 12 years of age) 1. Two positive tests for HIV infection by ERS test (ELISA/RAPID/SIMPLE) AND 2. Any one of the following criteria: a. Significant weight loss (> 10% of body weight) within last one month/Cachexia (not known to be due to a condition other than HIV infection). AND Chronic diarrhea (intermittent or continuous) > 1 month duration or prolonged fever (intermittent or continuous) > 1 month duration b. Tuberculosis: Extensive pulmonary, disseminated, miliary, extra-pulmonary tuberculosis. c. Neurological impairment preventing independent daily activities, not known to be due to the conditions unrelated to HIV infection (e.g. trauma) d. Candidiasis of the esophagus (diagnosable by oral candidiasis with odynophagia) e. Clinically diagnosed life-threatening or recurrent episodes of pneumonia, with or without etiological confirmation f. Kaposi’s Sarcoma g. Other conditions: - Cryptococcal meningitis - Neuro toxoplasmosis - CMV retinitis - Pencillium marneffei - Recurrent herpes zoster or multidermatomal herpes infection - Disseminated molluscum contagiosum

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Diagnosis of HIV infection • HIV infection is diagnosed on the basis of blood tests using three different ELISA/ Rapid/simple tests using different antigen preparation. • AIDS cases are diagnosed on the basis of two different ELISA/Rapid tests on different antigens and presence of AIDS related opportunistic infections. • Western Blot test is used for confirmation of diagnosis of indeterminate ELISA tests.

Mucocutaneous Manifestations of HIV Infection Mucocutaneous diseases are amongst the first recognized clinical manifestations of AIDS. Over the past decade, it has become increasingly clear that cutaneous disorders are not only associated with terminal immunodeficiency but occur throughout the course of HIV infection. This may be due to impairment of the skin immune system as evidenced by the reduced epidermal Langerhans cell population, which explains the development of opportunistic infections and neoplasms of the skin and mucous membranes in these patients. Mucocutaneous disorders remain one of the most important clinical markers of the stages of HIV infection from time of seroconversion. They range from urticarial viral exanthema to a myriad of cutaneous opportunistic infections or malignancies. They function as visual markers in assessing the progression of HIV disease. Cutaneous disorders occur more frequently as HIV infection advances and immune function deteriorates. They affect between 80% and 95% of HIV infected patients. Cutaneous disorders during HIV infection are numerous. Some have drawn attention because of their onset, defines some of the Center for Disease Control and Prevention (CDC), acquired immunodeficiency syndrome (AIDS) clinical categories, e.g. oral candidiasis, zoster, herpes simplex, oral hairy

leukoplakia and Kaposi’s sarcoma, but most have been documented solely in case reports. Mucocutaneous disorders are commonly the indication for initial HIV serotesting and they are listed in table. Mucocutaneous disorders as indicators for HIV serotesting A. Disorders strongly associated with HIV infection 1. Candidiasis-oropharyngeal (Figs. 32.1 and 32.2) or recurrent vulvovaginal 2. Herpes zoster-necrotic (Fig. 32.3), multidermatomal or disseminated 3. Chronic herpes simplex infection (Fig. 32.4) 4. Oral hairy leukoplakia (Fig. 32.5) 5. Papular eruption of HIV (Fig. 32.6) 6. Molluscum contagiosum-face involvement in an adult or giant molluscum contagiosum (Fig. 32.7) 7. Proximal white subungual onychomycosis 8. Kaposi’s sarcoma B. Disorders commonly associated with HIV infection 1. Any sexually transmitted disease-indicative of unsafe sexual behaviour 2. Signs of injected drug use C. 1. 2. 3.

Disorders associated with HIV infection Generalized lymphadenopathy Psoriasis vulgaris-explosive onset Seborrheic dermatitis-in an adult extensive and refractory to therapy 4. Aphthous ulcers-recurrent, refractory to therapy 5. Crusted scabies

Xerosis/acquired ichthyosis and giant molluscum contagiosum are characteristically seen in group IV of HIV disease whereas oral candidiasis, oral aphthae, papular dermatitis of HIV and psoriasis are early warning signs. Moreover, with progression of HIV disease, the number of dermatoses goes on increasing. Common dermatoses assume aggressive postures (Figs 32.8 to 32.13) and some rare dermatoses (Figs 32.14 and 32.15) also present.

Treatment • There is no cure for AIDS at this time. However, treatments are available that can

Human Immunodeficiency Virus Infection (HIV) and AIDS

Fig. 32.1: Oral candidiasis—curdy white deposits over the tongue

Fig. 32.2: Hyperplastic candidiasis of the tongue

Fig. 32.3: Herpes zoster—necrotic lesions of herpes zoster along a thoracic dermatome

Fig. 32.4: Herpes genitalis—non-healing impetiginized ulcers over the glans penis and prepuce

Fig. 32.5: Oral hairy leukoplakia—un-removable white striations on the side and dorsa of tongue

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Fig. 32.6: Papular eruption of HIV- itchy papular eruption over the back

Fig. 32.7: Molluscum contagiosum—giant lesions over the face

Fig. 32.8: Genital warts—multiple verruca vulgaris like genital warts

Fig. 32.9: Tinea versicolor—extensive macular lesions over the neck with cervical lymphadenopathy

Fig. 32.10

Fig. 32.11

Figs 32.10 and 32.11: Extensive tinea corporis and cruris lesions in a HIV patient

Human Immunodeficiency Virus Infection (HIV) and AIDS

Fig. 32.12: Secondary syphilis—pigmented lesions in the palms

Fig. 32.14: Cryptococcosis—hemorrhagic crusted papular lesions over the face

Fig. 32.13: Secondary syphilis—hyperkeratotic scaly plaques over the lower legs

Fig. 32.15: Cryptococcosis—molluscum contagiosum like lesions over the chest

improve the quality of life of those suffering the infection. • Use of condom during sexual acts should be encouraged. • Patients need counselling at the first visit apart from the general and specific treatments.

• Antiretroviral therapy is discussed in next chapter. • Opportunistic infections are treated with appropriate therapeutic agents. With Highly Active Retroviral Therapy (HAART), the prevalence of mucocutaneous disorders in HIV infected patients is coming down.

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33

Antiretroviral Therapy (ART)

Development of Antiretroviral Therapy (ART) • Zidovudine was first tested on humans in 1985 and introduced for treatment in March 1987. • Zalcitabine (ddC), didanosine (ddI), and stavudine (d4T) were introduced between 1991-1994. • Between December 1995 and March 1996, three protease inhibitors (PIs)-indinavir (IDV), saquinavir (SQV), and ritonavir (RTV) got approval. • 1996 onwards, combination therapy, highly active antiretroviral therapy (HAART) began to spread irreversibly. • In 1995, David HO came out with his slogan “hit hard and early”. • By June 1996, first NNRTI (nevirapine), a third drug class of antiretroviral drugs was licensed. Soon after another PI, nelfinavir, also arrived. • In 1996-97, some patients began to complain of fat stomach and buffalo hump with PIs but retained their thin facies and thin legs. • In 1998, a term lipodystrophy was used to describe the characterstic fat distribution that patients on HAART had developed. • In1999 “Mitochondrial toxicity” hypothesis emerged as the reason behind lipodystrophy.

• By year 2000, many strict recommendations got revised. “Hit HIV hard, but only when necessary” now heard more than” hit hard and early”. • Despite all skepticism, HAART can often achieve miracles e.g., cryptosporidiosis and Kaposi’s sarcoma simply disappear. Once daily regimens, even twice weekly regimens are coming. • New classes of drugs are appearing- co receptor antagonists, attachment-, integrase, and maturation inhibitors. • Since 1995, protease inhibitors (PIs) have revolutionized the treatment of HIV infection, but in recent years they have been criticized for their high pill burden and side effects. They remain an essential component of HAART especially for treatment experienced patients. With growing knowledge of mitochondrial toxicity of nucleoside analogs and the introduction of easy to take PIs, boosted PIs, this class of drugs is currently experiencing something of renaissance. Boosting with small doses of ritonavir is based on the fact that ritonavir a very potent inhibitor of the isoenzyme 3A4, a subunit of the cytochrome P450 hepatic enzyme system, allows boosting of the most important pharmacokinetic parameters of all

Antiretroviral Therapy (ART) PIs (except nelfinavir), maximum concentration, trough levels, and half life. Boosting is usually indicated by addition of “/r” after the drug name. • Reduction in the cost of ART from INR 35000/month (in year 2000) to approx. INR 1000/month made ART affordable. There is further chance of 20% price reduction.

Goals of Antiretroviral Therapy Eradication of HIV infection cannot be achieved with available antiretroviral regimens. Therefore, once the decision is made to initiate therapy, the primary goals of antiretroviral therapy are: 1. Reduction of HIV-related morbidity and mortality 2. Maximal and durable suppression of viral replication 3. Preservation and/or restoration of immunologic functions 4. Improvement of quality of life Currently available antiretroviral drugs have been classified in the Table 33.1. Antiretroviral Drugs 1. Nucleoside reverse transcriptase inhibitors (NRTIs): Their target is the HIV enzyme reverse transcriptase. 2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): The target enzyme is

reverse transcriptase. However, NNRTIs bind directly and noncompetitively to the enzyme at a position in close proximity to the substrate binding site for nucleosides. The resulting complex blocks the catalyst activated binding site of the reverse transcriptase. This, in turn, can bind fewer nucleosides, slowing polymerization down significantly. In contrast to NRTIs, NNRTIs do not require activation within the cell. The three available NNRTIs are nevirapine, delavirdine and efavirenz. 3. Protease inhibitors (PIs): The HIV protease cuts the viral gag-pol polyprotein into its functional subunits. If the protease is inhibited and proteolytic splicing prevented, non-infectious virus particles will result. 4. Entry inhibitors: There are three crucial steps for entry of HIV into the CD4+ T-cell. a. Binding of HIV to the CD4 receptor (target of attachment inhibitors), b. Binding to coreceptors (target of coreceptor antagonists), and finally c. Fusion of virus and cell (target of fusion inhibitors) 5. Integrase inhibitors: Integrase, along with reverse transcriptase and protease, is one of the three key enzymes in the HIV replication cycle. This enzyme is involved in the integration of viral DNA into the host genome, and is essential for the proliferation

Table 33.1: Currently available antiretroviral drugs

NRTI

NNRTI

PI

Azidothymidine(AZT)

Nevirapine (NVP)

Indinavir (IDV)

Stavudine (d4T)

Efavirenz (EFV)

Nelfinavir(NFV)

Didanosine (ddI)

Delaviridine(DLV)

Saquinavir(SQV)

Zalcitabine (ddC)

Ritonavir(RTV)

Abacavir (ABC)

Amprenavir(APV)

Tenofovir (TFV)

Lopinavir(LPV)

Emtricitabine(FTC)

Atazanavir(ATV)

Lamivudine (3TC)

Fosamprenavir(FPV)

* Fusion inhibitor: Enfuviritide

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Essentials in Dermatology of HIV. Integrase inhibitors are occasionally falsely classified as entry inhibitors. However, unlike the latter, they do not prevent entry of the virus into the cell. 6. Maturation inhibitors: The so-called maturation inhibitors inhibit HIV replication in a very late phase of the HIV reproduction cycle, i.e., by the budding or maturation of new virions. As is the case for integrase inhibitors, 2005 can be counted as the introductory year.

Highly Active Antiretroviral Therapy (HAART) It is a combination of different classes of antiretroviral in order: to achieve maximal (below level of detection) and most durable suppression of viral replication; prevent emergence of drug resistant mutants and to improve survival and quality of life. HAART has drawbacks of high cost, not being a cure, has short and long term side effects, drug interactions, need for stringent adherence, and risk of viral resistance. The characteristics of an ideal first line ART are that it should be affordable, effective and well tolerated, potent and robust, minimal drug inter-/contra-actions, appropriate for use in TB and pregnancy, and stable in tropical conditions Indications for Antiretroviral Therapy • Antiretroviral therapy is recommended for all patients with history of an AIDS-defining illness or severe symptoms of HIV infection regardless of CD4+ T cell count. (AI) (WHO clinical stage IV). • Antiretroviral therapy is also recommended for asymptomatic patients with 100,000 copies/mL most experienced clinicians defer therapy but some clinicians may consider initiating treatment. (CII). • Therapy should be deferred for patients with CD4+ T cell counts of >350 cells /mm3 and plasma HIV RNA 1,000 copies/mL genotypic resistance testing prior to initiation of therapy (BIII) should be considered; if therapy is to be deferred, resistance testing may still be considered (CIII).

ART Regimens Not Recommended • Monotherapy should not be used as it is less potent and does not have sustained antiviral activity. • Dual NRTI therapy has not demonstrated potent and sustained antiviral activity as compared to three-drug combination regimens. • Didanosine + stavudine combination can result in a high incidence of toxicities, particularly peripheral neuropathy, pancreatitis, and lactic acidosis. • Stavudine + zidovudine combination should be avoided because of the demonstration of antagonism in vitro and in vivo. • Didanosine + tenofovir combination has high failure rate of therapy, higher toxicity (pancreatitis). • Zalcitabine containing regimens are less convenient (given three times daily) and more toxic.

Follow-up of Patients on HAART Two surrogate markers are routinely used to determine indications for treatment and to monitor the efficacy of therapy: CD4+ T cell count and plasma HIV RNA (or viral load). The CD4+ T cell count should be determined every three to six months to (1)to determine when to start ART; (2) to assess immunologic response to ART; and (3) to assess the need for initiating chemoprophylaxis for opportunistic infections. Plasma HIV RNA (viral load) should be monitored every 2-8 weeks at initiation or for change in therapy and to confirm potency of the new regimen. In patients on stable ART, viral load should be monitored every 3-4 month or if clinically indicated. Efficacy of HAART is determined by clinical evaluation (weight gain, resolution of OI), viral load reduction (undetectable levels after 24 weeks), and CD4 cell counts (increase by 100-150 cells/mm3/ year).

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Adverse Effects of Antiretroviral Drugs Gastrointestinal problems are the most common side effects of almost all antiretroviral drugs nucleoside analogs, NNRTIs and particularly protease inhibitors – and occur especially during the early stages of therapy. Typical symptoms include abdominal discomfort, loss of appetite, diarrhea, nausea and vomiting. Heartburn, abdominal pain, meteorism and constipation may also occur. Nausea is a common symptom with zidovudine-containing regimens; diarrhea occurs frequently with zidovudine, didanosine and all PIs, particularly with ritonavir and nelfinavir, as well as with saquinavir, lopinavir atazanavir and tipranavir. Treatment with zidovudine rarely leads to a severe form of gastritic pain, nausea and vomiting in the early phase of therapy, in which case it should be discontinued. Serious Adverse Effects of HAART NRTI 1. Lactic acidosis mostly related to stavudine and didanosine, less in patients on zidovudine, abacavir and lamivudine. Risk factors are obesity, female sex, pregnancy and therapy with ribavirin or hydroxyurea, a diminished creatinine clearance and a low CD4+ T-cell nadir. 2. Hepatic steatosis, is probably caused by mitochondrial toxicity and usually occurs after more than 6 months on treatment 3. Pancreatitis - Up to 7 % of patients treated with didanosine suffer from pancreatitis. Occasionally, stavudine, lamivudine and zalcitabine cause pancreatitis too. 4. Hypersensitivity reactions-especially in patients on abacavir. 5. Anemia especially in patients on treatment with zidovudine 6. Peripheral polyneuropathy mostly caused by the zalcitabine, didanosine and stavudine. It can present as paresthesia and pain in hands

and feet or distal symmetrical sensorimotor paralysis 7. Myopathy, 8. Lipoatrophy

NNRTI 1. Rash-Nevirapine and delavirdine may cause a slight rash in 15 to 20% of patients, 5 to 10% of which discontinue treatment. The rash is seen less frequently on efavirenz therapy, where only 2 % of the patients discontinue the drug. The NNRTI allergy is a reversible, systemic reaction and typically presents as an erythematous, maculopapular, pruritic and confluent rash, distributed mainly over the trunk and arms. Fever may precede the rash. Further symptoms include myalgia (sometimes severe), fatigue and mucosal ulceration. The allergy usually begins in the second or third week of treatment. Women are more often and more severely affected. If symptoms occur later than 8 weeks after initiation of therapy, other drugs should be suspected. 2. Stevens Johnsons Syndrome 3. TEN 4. Hepatitis-hypersensitive hepatitis often occurs within the first 12 weeks. Liver toxicity occurs more commonly in patients on nevirapine than on other antiretroviral drugs. 5. Neuro-psychiatric-common in patients on treatment with efavirenz. It includes dizziness, insomnia, nightmares, mood fluctuations, depression, depersonalization, paranoid delusions, confusion and suicidal ideation. These side effects are observed mainly during the first days and weeks of treatment. Discontinuation of therapy becomes necessary in only 3 % of patients.

PI 1. Renal stones- occur particularly on indinavir treatment,

Antiretroviral Therapy (ART) 2. Hepatitis, PIs can lead to hepatotoxicity at any stage during the course of treatment. Patients with chronic viral hepatitis are particularly at risk. One possible cause is an immune reconstitution syndrome on HAART, with increased cytolytic activity against the hepatitis viruses. Among the PIs, toxic hepatitis is seen most frequently in patients on boosted atazanavir, indinavir and tipranavir, a novel non-petidic protease inhibitor. 3. Rash 4. Dyslipidemia 5. Glucose intolerance 6. Lipodystrophy 7. Osteoporosis

Change of Therapy Treatment Regimen Failure Virologic failure can be defined as incomplete or lack of HIV RNA response to antiretroviral therapy: • Incomplete virologic response is defined as repeated HIV RNA >400 copies/mL after 24 weeks or >50 copies/mL by 48 weeks in a treatment-naïve patient initiating therapy. • Virologic rebound is repeated detection of HIV RNA after virologic suppression i.e. repeated HIV RNA level >400 copies/mL after prior suppression of viremia to 10/1999 population 83. Which of these combination is acceptable in HIV – leprosy patient? A. Rifampicin – Zidovudine B. Rifampicin – Saquinavir C. Rifampicin – Nelfinavir D. Rifampicin – Indinavir 84. “Small bowel syndrome” occurs with A. Clofazimine B. Ethionamide C. Pefloxacin D. Rifapentine 85. The zoological name of nine banded armadillo A. Dasypus novemcinctus B. Erinaceus europaeus C. Citellus tridecemlineatus D. Tamias sibiricus 86. Most common procedure done for lagophthalmos A. Medial tarsorrhaphy B. Lateral tarsorrhaphy C. Temporalis muscle facial transfer D. Frontalis muscle facial transfer 87. Chaulmoogra oil as a therapy for leprosy was first introduced formally by A. Hansen B. Mouat C. Danielssen D. Sheskin 88. Ridley and Jopling recommended five systems of classification of leprosy in the year A. 1987 B. 1962 C. 1943 D. 1981 89. The first use of dapsone for leprosy was by A. Cochrane B. Faget C. Johansen D. Peterson

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Essentials in Dermatology 90. Thalidomide was found to be used in the treatment of erythema nodosum leprosum by A. Mouat B. Danielssen C. Peterson D. Sheskin 91. WHO recommended the use of multi drug therapy for leprosy in the year A. 1981 B. 1976 C. 1957 D. 1990 92. The first person to use dapsone orally were A. Faget and Muir B. Lowe and Smith C. Wade and Rodriguez D. Motta and Zuniga.

93. Gerhard Henrik Armauer Hansen was a A. Mexican B. American C. Norwegian D. Canadian. 94. Evidence of leprosy in India dates back to A. 2000 BC B. 50 AD C. 1000 AD D. 600 BC 95. Prior to 1943, the treatment of leprosy continued to be A. Chaulmoogra oil B. Intravenous Promin C. Diasone D. Rifampicin

Some Useful Medical Mnemonics

Some Useful Medical Mnemonics

A mnemonic is a device or code that helps one to memorize something. It is derived from the Greek term mnemon meaning “mindful”. In other words, a mnemonic helps one to keep something in mind. Mnemonics have been established as a useful tool in teaching a subject. Although mnemonics have limitations and should not replace traditional methods of teaching and learning, they are a useful education tool. Good mnemonics can increase the speed and amount of retained factual information, especially during stressful situations, such as examinations. A mnemonic is of great help in recalling the features of certain conditions, for example in systemic lupus erythematosus, the mnemonic ANTINUCLEAR A for antinuclear antibody, N for neurologic disorders such as seizures or psychosis, T for thrombocytopenia or lymphopenia or leucopenia or hemolytic anemia, I for immunologic features like positive LE cell preparation or anti ds DNA or anti sm antibodies or a positive test for syphilis, N for nasopharyngeal or oral ulcers, U for urinary abnormalities like proteinuria or casts, C for cutaneous discoid rash,

L for light sensitivity, E for effusions – pleural or pericardial, A for arthritis of two or more joints and R for a rash in the malar area This mnemonic enables students to recall the modified criteria confidently and quickly when examining a patient. In the mnemonic BIT CAFÉ for café au lait spots, the commonest condition seen by clinicians is placed last B for blooms, I for idiopathic, T for tuberous sclerosis, C for congenita (dyskeratosis), A for ataxia telangiectasia, F for Fanconi’s and E for elephant man (neurofibromatosis) The possible causes of erythema nodosm are recalled by the mnemonic NODOSUM NO cause in 60%, D for drugs, O for oral contraceptives, S for sarcoidosis, U for ulcerative colitis and M for microbiology: bacterial, viral, yersinia, tuberculosis, leprosy, deep fungal infections Seven P’s in telogen effluvium pregnancy,

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Essentials in Dermatology protein depletion, pills, propranolol, pyrexia, parturition and psychic stress Seven P’s in lichen planus purple, polygonal, planar or flat, papules, pruritic, persistent and penile Cockayne’s syndrome lies in COCKAYNE’S C for CNS defects, O for lipOdystrophy, C for color which is hyperpigmentation, A for auditory symptom of deafness, Y for microencephalY, N for normal pressure hydrocephalus, E for eye lesion of salt and pepper retina and S for short Describing skin lesions LES. T CABS Location and distribution (e.g. bilateral/symmetrical) Erythema (e.g. yes or no) Surface features (e.g. scale, verrucous) Type (e.g. papule, nodule, vesicle) Color (e.g. violaceous, blue) Arrangement (e.g. grouped) Border/shape (e.g. linear, serpiginous) Special sites/systemic (e.g. oral, nails, scalp) Generalized skin hyperpigmentation “With generalized, none of the skin is SPARED” Sunlight Pregnancy Addison’s disease Renal failure Excess iron (hemochromatosis) Drugs (e.g. amiodarone, minocycline)

Painful cutaneous nodules BENGAL CO Blue rubber bleb nevus Eccrine spiradenoma Neurilemmoma/neuroma Glomus tumor Angiolipoma/angioleiomyoma/angiosarcoma Leiomyoma Cutaneous endometriosis/calcinosis cutis Osteoma cutis White patch of skin “Vitiligo PATCH” Vitiligo Pityriasis alba/post-inflammatory hypopigmentation Age related hypopigmentation (e.g. idiopathic guttate hypomelanosis) Tinea versicolor, tuberous sclerosis (ash-leaf macules) Congenital birthmark (e.g. hypomelanosis of Ito) Hansen’s disease (leprosy) Common causes of leukocytoclastic vasculitis “VASCULITIS” Viral (e.g. hepatitis B and C) Autoimmune (systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis) Streptococci, staphylococci, Henoch-Schönlein purpura Cryoglobulins, cryofibrinogens, Churg Strauss/ Wegener’s granulomatosis Ulcerative colitis, urticarial vasculitis Lymphoproliferative disease (hairy cell leukemia) Infectious (endocarditis, meningococcemia, gonococcemia, rocky mountain spotted fever) Thiazides, phenothiazines, and other drugs Immune complex reactions, iodides, idiopathic Sulfa drugs (septran), penicillin, and other antibiotics Non-scarring alopecia TOP HAT Telogen effluvium, Tinea capitis Out of iron, zinc Physical-trichotillomania, traction alopecia Hormonal-hypothyroidism, androgenic Autoimmune-alopecia areata, anagen effluvium Toxins-heavy metals, chemotherapy

Some Useful Medical Mnemonics Behcet’s syndrome: Diagnostic criteria PROSE* Pathergy test Recurrent genital ulceration Oral ulceration (recurrent) Skin lesions (e.g. erythema nodosum, subcutaneous thrombophlebitis, cutaneous hypersensitivity) Eye lesions (e.g. iridocyclitis, chorioretinitis) * Oral ulceration is central criterion, plus any 2 others Focal dermal hypoplasia syndrome/Goltz syndrome “FOCAL” Female sex (85–90%) Osteopathia striata Coloboma Absent ecto-, meso-, and neuro-dermis elements Lobster claw deformity SLE (Systemic Lupus Erythematosus) diagnosis SOAP BRAIN MD* Serositis Oral/nasal ulcers Arthritis Photosensitivity Blood (cytopenia) Renal involvement ANA Immune (typical antibodies e.g. dsDNA, anti-Sm) Neurologic (e.g. Seizures, stroke) Malar rash Discoid rash * 4 out of 11 criteria needed for diagnosis Henoch-Schonlein purpura: signs and symptoms NAPA Nephritis Arthritis, arthralgias Purpura, palpable (especially on lower extremities) Abdominal pain (intussusception to be ruled out) Classification of hypersensitivity reactions “ACID”

Type I Anaphylaxis Type II Cytotoxic - mediated Type III Immune - complex Type IV Delayed hypersensitivity Multiple Endocrine Neoplasia: Each of the MENs is a disease of three or two letters plus a feature. MEN I is a disease of 3 P’s (pituitary, parathyroid, and pancreas) plus adrenal cortex MEN II is a disease of 2 C’s (carcinoma of thyroid and catacholamines [pheochromocytoma]) plus parathyroid for MEN IIa or mucocutaneous neuromas for MEN IIB (aka MEN III) WBC Count: “Never Let Mom Eat Beans” and “60, 30, 6, 3, 1” Neutrophils 60% Lymphocytes 30% Monocytes 6% Eosinophils 3% Basophils 1% LR6 SO4 3. Which cranial nerve controls which eye muscle? Lateral rectus sixth nerve, superior oblique fourth, rest third. Bones, stones, groans and psychic moanssymptoms of an elevated serum calcium level. C 3, 4 and 5, keeps your diaphragm alive. S 2, 3 and 4, makes a mess on the floor. Psoriasis: Pathophysiology PSORIASIS : Pink Papules/ Plaques/ Pinpoint bleeding (Auspitz sign)/ Physical injury (Koebner phenomenon)/ Pain Silver Scale/ Sharp margins Onycholysis/Oil spots Rete Ridges with Regular elongation Itching Arthritis/ Abscess (Munro) Stratum corneum with nuclei, neutrophils Immunologic Stratum granulosum absent/ Stratum Spinosum thickening

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Essentials in Dermatology Delay in wound healing DID NOT HEAL: Drugs Infection/ Icterus/ Ischemia Diabetes Nutrition Oxygen (hypoxia) Toxins Hypothermia/Hyperthermia Edema Acidosis Local anesthetics Cutaneous inflammation patterns “Pus of Pig Valve”· Remove the vowels: PSFPGVLV: Psoriasiform Spongiotic (eczematous) Folliculitis Panniculitis Granulomatous Vasculopathic Lichenoid Vesiculobullous Clubbing causes CLUBBING: Cyanotic heart disease Lung disease (hypoxia, lung cancer, bronchiectasis, cystic fibrosis) UC/Crohn’s disease Biliary cirrhosis Birth defect (harmless) Infective endocarditis Neoplasm (esp. Hodgkins) GI malabsorption Albinisim type I vs. type II “One has None. Two Accumulates”: Type I: have no pigment. Type II: No pigment at birth but accumulates as person ages. Malignant melanoma: 3 sites with poor prognosis BANS:

Back of Arm Neck Scalp Symptoms of hyperthyroidism Remember the following mnemonic when evaluating patients for hyperthyroidism: S: Sweating T: Tremor or Tachycardia I: Intolerance to heat, Irregular menstruation, and Irritability N: Nervousness G: Goiter and Gastrointestinal (loose stools/ diarrhea). 5 T’s of early cyanosis: Tetralogy, Transposition, Truncus, Total anomalous, Tricuspid atresia Causes of hematuria Use the mnemonic SITTT as an aid in evaluating the cause of hematuria: S: Stone I: Infection T: Trauma T: Tumor T: Tuberculosis Causes of postoperative fever Remember the following mnemonic when determining the possible cause (s) of fever in a patient who has recently undergone a surgical procedure: the 5 W’s (or 6 W’s) Wind: The pulmonary system is the primary source of fever in the first 48 hours. Wound: There might be an infection at the surgical site. Water: Check intravenous access site for signs of phlebitis. Walk: Deep venous thrombosis can develop due to pelvic pooling or restricted mobility related to pain and fatigue. Whiz: A urinary tract infection is possible if urinary catheterization was required. Also Wonder drugs - drug fevers.

Some Useful Medical Mnemonics Proven MI (Myocardial infarction), should be met by M.O.N.A. M = morphine O = oxygen N = nitrates A = aspirin Caveat: If right ventricular MI suspected, hold the Nitrates. Aortic Branches: ABC’S Aortic arch gives off the Brachiocephalic trunk, the left Common Carotid, and the left Subclavian artery Argyll-Robertson Pupil—syphilitic pupil: Accommodation reflex present, Pupillary reflex absent due to damage at pretectal area. Also called the “prostitute’s pupil” (accommodates but does not react). Arterial occlusion: pain pallor pulselessness paresthesias Causes of Pancreatitis BAD SHIT Black scorpion bite Alcohol Drugs (tetracycline, azathioprine, sulfa) Stones (gallstones) Hyperlipidemia Idiopathic Trauma Microcytic Anemia: “TICS”Thalassemia Iron deficiency Chronic disease Sideroblastic anemia Kawasaki’s disease: ”SCREAM FEVER” S - sausage fingers

C - conjunctival redness R - rash E - extremity involvement A - adenopathy M - mucosal erythema FEVER – fever Eosinophilia: “NAACP” N - Neoplasm A - Allergy A - Addison’s C - Cirrhosis, CVD P - Parasite (visceral larva migrans), Periarteritis nodosa Endocarditis: “FAME” F - FEVER A - ANEMIA M - MURMUR E - ENDOCARDITIS Tumors that go to bone: “Kinds of tumors leaping primarily to bone” K - Kidney O - Ovarian T - Testicular L - Lung P - Prostate T - Thyroid B – Breast Hypercalcemia: “SHAMPOO DIRT” S - Sarcoidosis H - Hyperparathyroidism, hyperthyroidism A - Alkali-milk syndrome M - Metastases, myeloma P - Paget disease O - Osteogenesis imperfecta O - Osteoporosis D - Vitamin D intoxication I - Immobility

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Essentials in Dermatology R - RTA T – Thiazides Henoch-Schonlein Purpura: “JARS” J - Joints A - Abdominal pain R - Renal S – Skin

Acute Rheumatic Fever: There are several for the major criteria, I use “JONES” J - Joints O - Obvious (cardiac) N - Nodules (subcutaneous nodules) E - Erythema marginatum S - Sydenham’s chorea

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy

Abscess: A localized collection of pus in a deep-seated cavity. Acantholysis: Separation of epidermal keratinocytes by loss of their intercellular connections causing the cells to become rounded. Acanthosis: Increase in thickness of prickle-cell layer of skin. Acne: Term used for a chronic inflammatory disease of the pilosebaceous follicles showing a keratinous plug, commonly referred to as acne vulgaris. Acrochordon: Skin tag. Actinic: Pertaining to rays or beams of light. Actinomycosis: A chronic suppurative infection of man and animals due to a species of Actinomyces. Ray-fungus disease. Acuminate: Sharp, pointed e.g., condyloma acuminata. Ainhum: Spontaneous separation of digit by constricting fibrous band. Albinism: Congenital hypopigmentation of skin, hair and eyes. Alkaptonuria: An inborn error of tyrosine metabolism leading to deposition of oxidized homogentisic acid in fibrous and cartilaginous tissue and characterized by dark urine. Allergy: Originally ‘altered immunological reactivity to antigens’ Alopecia: Loss of hair from normal hairy regions of the body. Amiantacea (pityriasis): Name given to a condition in which soft, asbestos-like scales adhere to scalp hairs. Anaphylaxis: Allergic reaction in which antigen releases mediators (cytokines) from antibodysensitized mast cells or basophils. Anetoderma: Macular atrophy of the skin. Angiokeratoma: A vascular lesion combining ectasia of dermal blood vessels with hyperkeratosis. Anhidrosis: Lack of sweating.

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Essentials in Dermatology Anthrax: Acute infective zoonosis of herbivorous animals, sometimes transmitted to man, caused by Bacillus anthracis and produces “Malignant pustule” in the skin (Greek anthrax charcoal). Anthropophilic: Preferring humans as host. Aphthae: Painful ulcers of the mucosae (usually oral cavity), often multiple and recurrent. Aplasia: Failure or lack of growth or development. Apocrine sweat glands: These tubular glands consists of two main parts – the coiled secretary gland and the straight excretory duct which opens into follicular canal just above the openings of sebaceous glands. They are distributed along the mammary line, i.e. axillae, areolae, periumbilical area, mons pubis, genital and perianal areas. Appendages: The epidermis gives rise to derivative structures (pilosebaceous unit, nails and sweat glands) called as appendages. Aquagenic: Caused by contact with water. Arachnodactyly: Increased length of fingers and toes, from resemblance to spider’s legs. Argyria: Ashen-grey discoloration of the skin and conjunctivae, resulting from chronic exposure to silver or its salts. Arthus phenomenon: Immunological reaction at site of injection of a substance (antigen) to which the recipient has previously formed precipitating-type antibodies, resulting in formation of antigen— antibody complexes causing tissue damage, especially of a vasculitic nature. Atopic disorders: The anaphylactic-type of disorder that results from IgE mediated reactions. Atopy: State of excessive formation of lgE antibody following exposure to common environmental allergens. Atrophy: A wasting, shrinkage, diminution or lack of tissue. Balanitis: Inflammation of glans penis (or glans clitoris). Balanoposthitis: Inflammation of glans penis and prepuce. Ballooning degeneration of epidermis: A type of degeneration of epidermal cells causing marked swelling of the cells with loss of intercellular bridges, occurs in viral vesicles. Basement membrane zone: Located beneath the basal layer, consists of the basement membrane and of the lamina lucida, anchoring fibrils, and reticulum fibres. Basidiobolomycosis: Disease caused by a genus of fungus causing subcutaneous phycomycosis. Bazin’s disease (tuberculous): Erythema induratum affecting legs of young women. Beau’s lines: Transverse depressions on the nails following acute illnesses or debilitating medical events. Behçet’s syndrome: Triad of orogenital ulceration and iritis. Pyoderma may occur and central nervous system and other organs may be involved. Bence-Jones protein: A low-molecular-weight protein found in urine of patients with myeloma. Berloque dermatitis: A streaky form of pigmented contact photodermatitis, usually seen in the neck but occasionally elsewhere, due to psoralen, as in bergamot oil in perfume. Besnier’s prurigo: Flexural form of atopic dermatitis.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Blaschko’s lines: A system of lines in the human skin along which many linear naevi and dermatoses arrange themselves. Boil: A term for furuncle Bourneville—Pringle syndrome: Tuberous sclerosis; epiloia. Bowen’s disease: Precancerous dermatosis; a form of carcinoma in situ. Bromhidrosis: Foul-smelling sweat, usually of axillary apocrine origin. Bubo: A swollen inflamed lymphatic gland, especially in neck, axilla or groin. Buerger’s disease: Thromboangiitis obliterans. Bulla: Bleb, blister. An elevated lesion of the skin containing clear fluid and over 0.5 cm diameter. Burrow: A track, passage or tunnel in the skin that houses a parasite, particularly the mite of scabies Buruli ulcer: Mycobacterium ulcerans infection, named after an area of the Nile in Uganda. Buschke—Loewenstein tumor: Giant condyloma acuminata. Callosity and corn: A callosity is a superficial circumscribed area of hyperkeratosis at a site of repeated friction, usually over a bony prominence on the hands or feet whereas a corn is a painful conical hyperkeratosis that occurs principally over toe joints (hard corn) and between toes (soft corn). Canities: Graying or whitening of hair. Carbuncle: A necrotizing pyogenic infection of the skin and subcutaneous tissue composed of a group of furuncles (boils). Casal’s necklace: Collar area of erythema and pigmentation around neck seen in pellagra. Castellani’s paint: Consists of basic fuchsin, carbolic and boric acids, acetone and resorcinol. Once widely used for epidermophytosis, now less so, or in modified form. Chancre: Usually, syphilitic ulcer developing at site of infection with T. pallidum; also, rarely, for lesion at inoculation site of sporotrichosis, tularemia or tuberculosis. Cheilitis: Inflammation of the lips. Cheiropompholyx: Blistering eruption of the hands. Cheloid: A more correctly derived spelling for Alibert’s KELOID. Alibert noted resemblance to feet of crayfish or crabs and hence the name. Chilblain: Lesion chiefly affecting fingers, toes and ears caused by a vascular response to low temperature (cold) and humidity. Chlamydia: Genus of tiny intracellular parasites classified as bacteria; the cause of psittacosis — lymphogranuloma venereum — trachoma group of infection. Chloasma (melasma): Patchy brownish pigmentation affecting particularly malar area of face. Chrysiasis: Deposition of gold within tissue. Clutton’s joints: Painless joint effusion (commonly of knees) in late congenital syphilis. Coccus, cocci: Spherical bacillus grouped in pairs, chains or clusters. Collagen: Collagen is the most abundant protein in the body and constitutes about 70% of the dry weight of the dermis. It serves as its major structural component and has remarkable tensile strength.

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Essentials in Dermatology Colloid bodies: Another name for Civatte bodies, are round or oval, 10 micrometer eosinophilic homogeneous bodies formed due to degeneration of epidermal cells and are extruded into the dermis. Comedo: A greasy plug in a sebaceous follicle. Condyloma: A wart-like growth due to hypertrophy of prickle-cell layer, commonly used for genital and perianal lesions of viral (acuminata) or syphilitic (lata) origin. CREST (CRST) syndrome: Calcinosis, Raynaud’s phenomenon, (Esophageal involvement), Sclerodactyly, Telangiectasia. Cryo: Meaning cold. CTCL: Cutaneous T-Cell Lymphoma. Cullen’s sign: Bluish staining around umbilicus usually denoting acute pancreatitis or ruptured ectopic pregnancy. Cushing’s syndrome: Due to adrenocortical hypertrophy. The term ‘Cushingoid’ is applied to the appearance caused by high-dose corticosteroid therapy. Cutis laxa: Laxity or fold-like formation of skin. Cyst: Any closed cavity or sac (normal or abnormal) with an epithelial, endothelial or membranous lining and containing fluid or semisolid material. Dactylitis: Inflammation or infection of a finger. Dandruff: Popular term for pityriasis capitis, a mild form of seborrheic dermatitis. Darier’s disease: Keratosis follicularis. Decalvans: Causing loss of hair, e.g. folliculitis decalvans. Decubitus ulcer: Bedsore; pressure sore due to prolonged recumbency without movement de Morgan’s spots (Campbell de Morgan’s spots): Cherry angiomas. Dermabrasion: Surgical technique of removal of superficial lesions of the skin by abrasive methods such as with high-speed rotary drills, or hand used dermabrader. Dermal-epidermal junction: The dermal-epidermal junction (DEJ) is a basement membrane zone (BMZ) that welds the epidermis to underlying dermis. It is undulated, forming dermal papillae (upward projections of the dermis into the epidermis) and rete ridges (downward projections of epidermis into the dermis). This DEJ is weakest at lamina lucida. Dermatoglyphics: It is the study of the highly characteristic epidermal ridge patterns of the volar skin of palms, soles, fingers and toes. Dermis: The dermis is formed by connective tissue having fibres (collagen, elastic and reticulin) and ground substance. It varies in thickness from about 1 mm on the face to 4 mm on the back and thigh. Dhobi (dhobie, dhoby): Indian washerman, ‘dhobie itch’ a colloquial term used by servicemen for tinea cruris. Diascopy: Examination of skin with exclusion of blood by firm pressure of glass, etc.; vitropression. DIC: Disseminated Intravascular Coagulation Ducrey’s Bacillus: Haemophilus ducreyi, the cause of chancroid. Duhring-Brocq disease: Dermatitis herpetiformis.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Dyskeratosis: Means faulty and premature keratinization of individual keratinocytes occurs in certain acantholytic diseases and epidermal neoplasias. Dysidrosis (better, dyshidrosis or pompholyx) literally, difficult sweating. Name given for an acute vesicular eruption of palms and/or fingers resembling ‘small boiled sago grains’ and previously thought to be caused by poral occlusion and sweat retention, hence the above name. Ecchymosis: Synonymous bruise. A macular red or purple or colored hemorrhage in skin or mucous membrane more than 2 mm in diameter. Eccrine sweat glands: They are tubular structures, which open on to the skin directly. The three parts of them are coiled glandular portion, the straight dermal ductal portion and spiral intraepidermal ductal portion. Sweat glands are most abundant on the palms, soles, forehead and axillae. These glands are highly developed and responsive part of the thermoregulatory apparatus. Ecthyma: A deep crusted pyogenic infection, usually on legs. Eczema: An inflammatory skin reaction characterized histologically by spongiosis and clinically by a variety of features, notably vesiculation (Greek ek out, zeein to boil). Ehlers-Danlos syndrome: A group of heritable disorders of connective tissue, characterized by hyperextensibility, fragility, easy bruising and poor skin healing, to varying degrees in different types. Elastic fibers: Elastic fibres constitutes about 3% of the dry weight of the dermis. The characteristic property of elastic fibres is that they can be stretched by 100% or more and still return to their original dimensions. ELISA: Enzyme-Linked Immunosorbent Assay. EMLA: Eutectic Mixture of Local Anesthetics. ENL: Erythema Nodosum Leprosum. Ephelis: Commonly, a freckle. Epidermis: The epidermis is continually renewing, stratified, squamous epithelium that keratinizes and gives rise to derivative structures (pilosebaceous unit, nails and sweat glands) called appendages. It is approximately 0.4 mm to 1.6 mm in thickness. The majority of the cells in the epidermis are the keratinocytes. Epidermotropism: Means presence of mononuclear cells in the epidermis with little or no spongiosis occurring in mycosis fungoides. Epiloia: A term coined to denote a triad of Epilepsy, Low Intelligence and Adenoma sebaceum. Epithelium: The cellular covering of the skin and mucous membranes. Epstein—Barr virus: A herpesvirus causing infectious mononucleosis, oral hairy leukoplakia. Erysipelas: An acute infection of the skin by the hemolytic streptococcus, St Anthony’s fire Erythema: Redness of the skin produced by vascular congestion or perfusion. Esthiomene: A destructive lesion of vulva or clitoris occurring in lymphogranuloma venereum associated with lymphedema. Exocytosis: Means presence of mononuclear cells in the epidermis in acute and subacute dermatitis.

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Essentials in Dermatology Favus: A fungal infection of the scalp, usually caused by Trichophyton schoenleinii. It forms a characteristic cup-shaped crust (scutula), which, on removal, exposes an oozing red surface. Fernandez reaction: A delayed-type of hypersensitivity reaction to Dharmendra antigen in leprosy. Fibroblasts: Fibroblasts are the most numerous of the cells found in loose connective tissue of dermis. They are the source of the ground substance, collagen and elastic fibers. Follicular plug: Hyperkeratosis distending a hair follicle opening. Fordyce angiomata: Scrotal angiomata. Fordyce spots: Ectopic sebaceous glands of inner surface and vermilion of lip and oral mucosa, appearing as creamy-coloured symptomless lesions. Fournier’s gangrene: Fulminating gangrene of the external genitalia. Fournier’s sign: Bowing of the tibia seen in osteitis deformans, syphilis and yaws. Fox-Fordyce disease: (Synonyms lichen axillaris, apocrine miliaria) intensely pruritic papular eruption involving apocrine ducts in axillae, breasts or genital area. Freckle: (Synonym ephelis) light-brown macules occurring in sun-exposed skin, especially in fairskinned persons. Frei’s disease: Lymphogranuloma venereum. Frei’s test: A diagnostic intradermal test of limited value for lymphogranuloma venereum. Functions of the skin: Main functions of the skin are protection, thermoregulation, sensory, storage organ, vitamin-D formation, absorption, excretion, immune surveillance, mechanical and cosmetic function. Furuncle: A localized painful nodular pyogenic infection originating around a hair follicle. Gangrene: Commonly used to describe necrotizing and sloughing lesions but more properly referring to death of tissue resulting from ischaemia. Ghon’s focus: Primary tuberculous complex of the lung. Giant cell: A cell with more than one nucleus. Langhans giant cell has peripheral ring of nuclei whereas foreign body giant cell has haphazard arrangement of nuclei. Gibert’s disease: Pityriasis rosea. Glabrous: Smooth; commonly used to designate smooth, hairless skin; properly skin without any hair follicles. Gottron’s sign: Erythematous papules over metacarpal and proximal interphalangeal joints in dermatomyositis. Granuloma: A chronic inflammatory lesion showing accumulations of macrophages which have undergone epithelioid transformation, with or without lymphocytes and multi-nuclear giant cells; more loosely, a nodular chronic inflammatory lesion arising in response to a variety of stimuli. Graves’ disease: Hyperthyroidism due to diffuse toxic goitre. Grenz zone: A zone of normal dermis overlying deeper pathological changes. Ground substance: Ground substance is an amorphous material that consists mainly of water, electrolytes, plasma proteins and mucopolysaccharides. A mucopolysaccharide consists of a longchain aminated polysaccharide (glycosaminoglycan) linked covalently to a polypeptide.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Gumma: A characteristic though inconstant lesion of tertiary syphilis, of a rubbery consistency and with a fibrous capsule, it consists of necrotic tissue and epithelioid, multinucleated and plasma cells. Also (rarely) used for tuberculous. Gynaecomastia: Enlargement of breasts. Hair: Hair structurally consists of a cuticle, cortex and medulla. These keratinous fibers are of two types in adults. Terminal hairs are thick, pigmented and long and are seen on the scalp, eyebrows, axillae and genital areas, etc. Vellus hairs are small in diameter, short and nonpigmented and therefore difficult to discern. Hair cycle: Hair grows at the rate of 0.3 mm per day and they undergo growth cycle. These recurring cycles consist of anagen (active growth phase), catagen (static growth phase) and telogen (shedding phase) phases. On the scalp, 80 to 85% of hair is in anagen phase and 15 to 20% in catagen and telogen phase. The anagen phase lasts for 2 to 5 years, a short catagen of few days and a telogen phase of 3 months. Hailey—Hailey disease: A term for benign familial pemphigus. Hamartoma: A benign tumor or tumor-like lesion composed of tissue normal for the body but inappropriate for the site; or abnormally mixed or overgrown. Broadly, naevoid anomaly. Hansen’s disease: A term for leprosy. After Hansen, who discovered the Mycobacterium leprae bacillus in 1873. Hartnup disease: A rare metabolic disorder comprising pellagra, cerebellar ataxia and indicanuria. Heberden’s nodes: Bony swellings of the distal interphalangeal joints of the hands, indicative of osteoarthritis. Henoch - Schonlein purpura: Anaphylactoid purpura. “JARS” J – Joints, A-Abdominal pain, R – Renal, S – Skin. Herpes: Originally used to designate a spreading or ‘creeping’ eruption. Now applied to herpes simplex, herpes zoster and herpes gestationis — all conditions in which a vesicular eruption appears to extend or ‘creep’ in clusters or in a linear fashion. Herpetiform-herpes-like. Grouped vesicles resembling herpes. Hess (capillary) test: A tourniquet test used to determine capillary fragility. Hiemalis: Pertaining to winter, e.g., dermatitis hiemalis. Hippocrates: Greek physician (460 BC- 377 BC), ‘The Father of Medicine’. Hippocratic oath, facies; aphorisms of Hippocrates; etc. Hippocratic nails: Broad, convex, clubbed nails; acropachy. Hirsutism: The growth of hair in women in the male sexual pattern but more commonly any abnormal degree of coarse hairiness. HIV: Human Immunodeficiency Virus. Hives: Term for urticaria; ‘nettle-rash’. Holocrine: Shedding completely, as applied to sebaceous glands, the secretion of which is formed by the complete disintegration of the glandular cells. Horner’s syndrome: Miosis, enophthalmos, ptosis and absence of sweating due to lesion of ipsilateral cervical sympathetic chain or ganglia.

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Essentials in Dermatology Hutchinson J’ Sir: British surgeon (1828—1913 AD). Outstanding figure in late 19th-century British medicine. Possessed an extraordinary visual memory, he made wide-ranging contributions to many aspects of medicine and surgery. His output was prodigious. ‘A most careful observer and fascinating teacher.’ Hutchinson’s teeth: Barrel-shaped incisors with a deep concentric notch seen in congenital syphilis. ‘Pegged’, ‘screwdriver’ teeth. Hutchinson’s triad: Interstitial keratitis, nerve deafness and tooth deformities in congenital syphilis. Hydropic degeneration of basal cells: A type of degeneration causing vacuolization of the basal cells, also called as liquefaction degeneration. It occurs in lupus erythematosus, dermatomyositis, lichen sclerosus et atrophicus, lichen planus, etc. Hypergranulosis: Increase in thickness of the granular layer of the epidermis. Hyperkeratosis: Increase in the thickness of stratum corneum of the epidermis. Ichthyol: A natural tar-like substance derived from bituminous deposits rich in fossilized fish. Ichthyosis: A group of disorders of keratinization characterized by fine scaling and a feeling of dryness of the skin (Greek ichthya rough fish skin from ichthys fish, osis). -id, -ide: In dermatology the term ‘ide’, ‘id’, denotes a reaction occurring in a part remote from the primary lesion, usually but not invariably due to an immunological reaction to the agent concerned or to its component parts e.g. tuberculide, syphilide, trichophytide. Idiopathic: Having no known cause. Impetigo: A contagious eruption of the skin caused by the Streptococcus/Staphylococcus. Incontinence of pigment: Loss of melanin from the cells of basal layer due to damage to these cells. It is taken up by macrophages in the dermis. Intertrigo: Inflammation of apposed skin surfaces such as groins, axillae and inframammary areas. Ischaemia: State of lack of blood supply to a part or organ; arterial insufficiency. Jarisch- Herxheimer reaction: A focal exacerbation of lesions when a disease of infective origin is treated with potent antimicrobial agents. Seen in treatment of early syphilis with penicillin. Kala-azar: Visceral form of leishmaniasis (Hindi kala black, Persian azar disease, poison). Also known as Dum-Dum fever after a town near Calcutta, India. Kaposi’s sarcoma: Multiple idiopathic haemorrhagic sarcoma. Kaposi’s varicelliform eruption: Disseminated primary infection with viruses of herpes simplex, vaccinia and perhaps Coxsackie A16, seen especially in atopic subjects. Now termed ‘eczema vaccinatum’ and ‘eczema herpeticum’. Kawasaki’s disease: Mucocutaneous lymph node syndrome. “SCREAM FEVER” S - sausage fingers, C - conjunctival redness, R-rash, E - extremity involvement, A-adenopathy, M - mucosal erythema, FEVER-fever Keloid: Alternative term for CHELOID and preferred by some in common usage. Kerion: An inflammatory granuloma of hair-bearing areas due to superficial fungal infection, particularly of zoophilic species.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Koebner’s phenomenon, reaction: The induction of a lesion of certain diseases such as psoriasis and lichen planus following physical or non-specific trauma to the unaffected skin. Isomorphic effect. Koch’s postulates, law: The law of specificity of bacteria. Four conditions must be satisfied to establish the causative organism of a specific disease: the organism must be present in every case; it must be isolated and grown in pure culture; when this is inoculated into susceptible animals it must reproduce the disease; and the organism must be grown again in pure culture. Koenen’s tumors: Periungual fibromata occurring in tuberous sclerosis. Kogoj’s spongiform pustule: Epidermal pustule containing polymorphonuclear leucocytes seen in active or pustular phases of psoriasis. Koilonychias: Spoon-shaped nails Koplik spots: Irregular red spots with grayish centres seen in oral mucosa during the prodromal period of measles. Kveim (Kveim-Siltzbach) test: A diagnostic test for sarcoidosis using intradermal injection of sarcoid tissue. Kwashiorkor: A disease of malnutrition in which the (African) hair becomes a lighter, reddish color (Ghanaian term for ‘rejected one’). Lamellar: A layer, leaf or plate; used to describe scaling. Langer’s lines: Cleavage lines in skin determined by the disposition of connective tissue in reticular layer. Langerhans cells: Important specialized dopa-negative dendritic mesodermal cells found in keratinized epithelia. They are morphologically distinctive type of macrophages, which are characterized by a folded nucleus, and distinct intracytoplasmic organelles called Birbeck granules. Langerhans cells perform immunological function in the skin. Langerhans layer: Another name for granular cell layer of epidermis. Langhans cells: Multinucleated giant cells, as found typically in tuberculous granulomas. Laser- Light Amplification by Stimulated Emission of Radiation. Leiner’s disease (syndrome): A desquamative erythroderma of due to C-5 complement deficiency affecting young infants and accompanied by diarrhoea, weight loss and increased susceptibility to infections. Lentigo: A pigmented macule having an increased number of melanocytes at the dermo-epidermal junction. Leprosy (synonym Hansen’s disease): A chronic mycobacterial disease affecting the skin and peripheral nervous system Leser-Trelat sign: Rapid development of pruritic seborrheic keratoses associated with internal malignancy. Letterer- Siwe disease: An acute form of generalized histiocytosis of infancy, with seborrhoeic eczemalike eruption and purpura. Leucoderma: Lack of normal pigmentation of the skin.

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Essentials in Dermatology Leucoplakia: Persistent white patches on mucous membranes not attributable to a known disease process. Libman-Sacks endocarditis: A verrucous endocarditis that may be associated with systemic lupus erythematosus. Lichen: An old term now restricted to a relatively small number of papular eruptions, of which lichen planus is the most com-mon (Greek leichen a tree-moss, lichen or liverwort). Lisch nodules: Pigmented iris hamartomas occurring in neurofibromatosis. Livedo: A cyanotic discolouration of the skin of reticulate, patchy or mottled pattern due to venous congestion or arterial disease. Louse: An ectoparasitic insect belonging to the order Anoplura or Mallophaga; dermatologically, head or body louse (Pediculus) or pubic louse (Phthirus). Lucio’s phenomenon: A distinctive reactional state in the course of diffuse lepromatous leprosy “Lucio leprosy”, “Lepra bonita”, a beautiful leprosy. Lues: A disguised designation for syphilis but originally a term for plague. Lupus: A term applied to lesions having an eroded or gnawed quality. Now confined to form of cutaneous tuberculosis, especially lupus vulgaris, and lupus erythematosus where it is better fitted to describe the discoid form. Lyell’s syndrome: Another term for toxic epidermal necrolysis. Originally also included staphylococcal scalded skin syndrome. -lysis meaning loosening, separation or rupture. Macrocheilia: Abnormal enlargement of lips. Madura foot: Name for mycetoma, a tumid granulomatous fungal infection of the foot. Named after Madura now Madurai, a town in South India. Majocchi’s granuloma: A trichophytic granuloma of the dermis. Malassezia: Name previously given to the dimorphic form of the lipophilic yeast Pityrosporum orbiculare. Malpighian layer: The basal and prickle-cell layers of the epidermis, also called as stratum malpighi. Mantoux test: Intracutaneous tuberculin test for tuberculosis. Marfan’s syndrome: A heritable disorder of connective tissue characterized by abnormally long extremities, arachnodactyly and ocular and cardiovascular anomalies Marjolin’s ulcer : Squamous cell epithelioma arising in an irritated scar tissue. Martorell’s ulcer : Hypertensive ulcer of the leg. Mast cell: Mastocyte widely dispersed mesenchymal cells found in the bone marrow, dermis and other tissues, the cytoplasm of which contains numerous metachromatically staining granules. Mast cells liberate histamines and various mediators during IgE mediated hypersensitivity responses. Mees’ lines: Horizontal whitish striations observed on nails in acute arsenical poisoning but also seen with other systemic disease.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Melanocytes: Melanocyte is a dendritic cell, which structurally resembles the octopus. Each melanocyte is in contact with 36 keratinocyte, together they form the so-called epidermal melanin unit. The main function of melanocyte is to synthesize melanin (Eumelanin or Pheomelanin). Melasma: Hypermelanosis of the face, seen chiefly in women; chloasma. Melkersson- Rosenthal syndrome: Recurrent facial paralysis, facial oedema, granulomatous cheilitis and other associated features. Micro: Pref. meaning small. Microabscesses: Small accumulations of cells in the epidermis or the subepidermal papillae. Three types of microabscesses are (i) Munro microabscess, composed of disintegrated neutrophils in the parakeratotic layer in psoriasis, (ii) Pautrier microabscess, composed of mononuclear cells and mycosis cells in the stratum malpighi in mycosis fungoides, and (iii) Papillary tip microabscess, composed predominantly of neutrophils in dermatitis herpetiformis. Miliary: Similar in size to a millet seed. Milium: A tiny white cyst containing lamellated keratin. Mite: Any small insect, e.g., scabies mite. Mitsuda’s antigen: A suspension of heat-killed leprosy bacilli used in an intradermal test for leprosy (Mitsuda’s reaction). Mole: Strictly, a circumscribed pigmented lesion of the skin but often applied to any raised accumulation of melanocytic nevus cells irrespective of pigmentation. Molluscum: A soft cutaneous nodule. Montgomery’s tubercles: Apocrine glands in the areola of the breast enlarged during pregnancy. Morgan’s folds (synonym Dennie-Morgan folds): Single or double infraorbital folds in children thought to be indicative of the atopic state. Morphoea: A circumscribed form of scleroderma. Mosaic: Patterned arrangement of small pieces, closely set appearance resembling a mosaic. Mycetoma: A term given to tumid and inflammatory fungal infections of deep tissues usually of the foot, due to various species of fungus. Mycosis fungoides: A CTCL lymphoma that may present as fungating masses. Myiasis: Disease caused by dipterous (fly) larvae. Nevus: A term for a circumscribed developmental lesion of skin or mucous membrane involving excess or deficiency of any one of the normal structures; cutaneous hamartoma. Nail unit: It is yet another epidermal appendage. It consists of nail matrix just underneath the proximal nail fold which gives rise to nail plate – a keratinized structure. The rectangular nail plate rests on a nail bed and is bounded on two sides by lateral nail folds. The cuticle seals the space between nail folds and nail plate. Necrobiosis: Physiological or normal cell death in the midst of living tissue. Neoplasm: ‘New growth’, tumor. A benign, premalignant, or malignant lesion consisting of proliferating cells.

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Essentials in Dermatology Nigricans: Blackish; properly, becoming dark. Nikolsky’s sign: Intra-epidermal cell separation or blister formation evoked by firm sliding pressure on unaffected skin of patients with pemphigus (especially pemphigus foliaceus) and, sometimes, epidermal necrolysis. Nit: The egg of the louse; or the encased embryo. Norwegian scabies: A form of extensive crusted scabies described by Boeck and seen in elderly, immunocompromised or mentally defective patients. Nummular: Assuming shape of coin, discoid. Obliterans: Destroying, obliterating. Ochre: A pigment of clay and iron oxide, of great antiquity; hence, yellow-red in color. Ochronosis: Grayish or bluish discolouration of connective tissue and cartilage due to deposition of a pigment derived from oxidized homogentisic acid, occurs in ALKAPTONURIA and in chronic exposure to phenol and phenolic compounds. Ointment: Semi-solid preparation in suitable base for application to the skin. Commonly used term for greasy preparations as opposed to creams. Onychia: Inflammation of nail matrix. Onychogryphosis: Thickening and over curvature of the nail resembling a ram’s horn. Onychoschizia splitting of nail plate into layers Onychotillomania: Habit of fiddling with or pulling pieces off the nail, an obsessional or psychopathic trait. Ophiasis: Snake-like, curling; applied to a form of alopecia areata. Orf: Ecthyma infectiosum. Highly contagious disease of sheep and goats caused by a parapoxvirus. May infect man by contact. Osler’s nodes: Tender erythematous lesions occurring on pads of fingers and toes, or palms and soles of patients with subacute bacterial endocarditis. Oxyuriasis: Infestation by worm of genus enterobius; enterobiasis. Pachydermoperiostosis: Hypertrophic osteoarthropathy with thickened skin. Pachyonychia: Abnormally thick nails. Paget’s disease, extramammary: A malignant plaque occurring in anogenital area or axillae and containing Paget cells. Paget’s disease of the nipple; mammary Paget’s disease: A marginated scaly or crusted lesion of the nipple containing intra-epidermal paget cells and associated with intraductal carcinoma of the breast. Panniculus: A layer of fat, covering sheet or garment. Papilloma: A nipple-like mass projecting from the surface of the skin. Papillomatosis: Upward proliferation of subepidermal papillae. Parakeratosis: Means retention of nuclei in the horny layer associated with a marked underdevelopment or absence of the granular layer, seen in psoriasis and other disorders

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Patch: A large macule, more than 2 cm in diameter; a term obsolete now. Pautrier’s abscess (microabscess): Focal collections of lymphocytes in the epidermis of patients with mycosis fungoides. Peau d’orange: A dimpling and induration of the skin, such as may overlie a mammary carcinoma (French, orange-skin). Pediculosis: A genus of parasitic lice infecting man and other primates, family Pediculidae Pelade: French term for alopecia areata. Pellagra: Sisease due to dietary deficiency of niacin and tryptophan (from Italian “pelle agra” rough skin). Pemphigus: A group of blistering diseases showing intra-epidermal bullae and acantholysis. Pemphigoid (‘bullous pemphigoid’): A blistering disease of the elderly with subepidermal bullae. Perleche: Angular cheilitis Petechia: A punctate haemorrhagic spot 1-2 mm in diameter. Peutz-Jeghers syndrome: Orificial and periorificial lentigines with hamartomatous intestinal polyps. Peyronie’s disease: Penile fibromatosis. Phagedaena: Rarely used term for a rapidly spreading or deepening ulcer. Phrynoderma: Dry skin with horny follicular papules, especially as seen in severe vitamin A or essential fatty acid deficiency (Greek phrynos toad, derma skin, from resemblance to toad skin). Phthiriasis: Infestation with any type of louse but usually confined to infestation with pubic lice. Phthirus (pubis): A genus of louse primarily affecting the pubic hair and occasionally other hairy areas. Piedra: A fungal infection of the hair forming superficial nodules on the shaft (Spanish piedra stone). Piezogenic: Name given to pedal papules formed of herniated fat, the result of weight bearing around the ankle. Pilosebaceous unit: It consists of a hair follicle containing hair and sebaceous glands opening into follicular canal of hair follicle. Plaque: An elevated area of skin 2 cm or more in diameter or lesion formed by coalescence of papules. Plummer-Vinson syndrome (synonym Patterson -Brown Kelly syndrome)- dysphagia, post-cricoid oesophageal webs, spoon-shaped fingernails and atrophic glossitis. Poikiloderma: Dappled or variegated pattern of pigmentation. Usually applied to condition combining this with telangiectasia and atrophy. Pompholyx: A general term for cheiro- (and podo-) pompholyx, used for an acute, often recurrent deeply seated vesicular or bullous eruption of palms and fingers of unknown cause (‘dysidrosis’). Porphyria: Name given to a group of inborn errors of metabolism (porphyrin synthesis). Prickle cell: An epidermal cell in the stratum spinosum, so named because of its spiny intercellular bridges. Prurigo: A term denoting a number of conditions characterized by intensely irritable papules with no obvious local cause.

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Essentials in Dermatology Pruritus: A sensation of itching. Pseudopelade: A morphological term for a pattern of follicular response to a variety of insults, often unknown, resulting in patches of complete loss of scalp hair. Psoriasis: A chronic, inflammatory skin disease consisting essentially of well-demarcated dull-red plaques, though with many variants. Mnemonic to remember features of PSORIASIS: Pink Papules/ Plaques/ Pinpoint bleeding (Auspitz’s sign)/ Physical injury (Koebner phenomenon)/ Pain Silver Scale/ Sharp margins Onycholysis/ Oil spots Rete Ridges with Regular elongation Itching Arthritis/ Abscess (Munro) Stratum corneum with nuclei, neutrophils Immunologic Stratum granulosum absent/ Stratum Spinosum thickening. Pterygium: Vascular lesions encroaching on the cornea; fusion of eponychium with proximal portion of nail (pterygium unguis); web of skin extending from mastoid to achromial process as in Turner’s syndrome (pterygium colli). Purpura: Focal haemorrhage into the skin. Pustule: A vesicle or bulla containing numerous neutrophils. Pyoderma: Any purulent skin condition. Queyrat, erythroplasia: An intra-epidermal carcinoma of male genital mucosa (glans and prepuce). Quinke’s oedema: Means angioedema. Rash: Term for any inflammatory skin eruption Raynaud’s disease: Primary idiopathic form of Raynaud’s phenomenon. Raynaud’s phenomenon: Paroxysmal pallor, numbness and coldness of the extremities, often followed by cyanosis, due to digital vasospasm. It occurs in a number of diseases, notably the collagen vascular diseases. Reiter’s syndrome: Non-specific urethritis, arthritis and iridocyclitis (uveitis). Patients may develop a rupioid psoriasiform skin lesions in soles (keratoderma blennorrhagica). Reticulate: Means lacy, webbed, net-like. Rhagades: Cracks; fissures, a term used in congenital syphilis sequelae. Rhinosporidiosis: A granulomatous nasal mycosis common in Sri Lanka and South India. Ringwom: Very old term for any ring-shaped eruption; more recently used for superficial fungal infections, dermatophytosis or tinea. Ritter’s disease: Another name for staphylococcal scalded skin syndrome. Rosacea: A condition characterized by erythema, telangiectasia and acneiform pustules commonly affecting the central part of the face, occasionally scalp or elsewhere. Also termed acne rosacea. Rowell’s syndrome: Lupus erythematosus with erythema multiforme-like lesions. Sabouraud’s medium (agar): A culture medium for fungi, containing peptone and dextrose. Samman’s syndrome (synonym yellow nail syndrome): Thick, curved, slow growing yellowish nails associated with lymphoedema.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Sarcoidosis: A multisystem disease of unknown cause, characterized by non-caseating granulomas. Sarcoptes: A genus of mites, the Sarcoptidac, ectoparasites of warm-blooded animals. Scabiesinfestation with Sarcoptes scabeii. Also called itch, mange, ‘seven-year itch’. Scale- a flat plate or flake of stratum corneum. Scar: Fibrous tissue replacing normal tissues destroyed by injury or disease. Scleroderma: A local or generalized hardening of the skin, usually referring to systemic sclerosis. Sclerosis: A localized or diffuse induration. Scratch: A linear incised superficial wound of the skin, as with the fingernails, thorn, etc. Scrofula: Primary tuberculosis of cervical glands, with or without ulceration of overlying skin. Scutularis: A saucer-shaped depressed lesion, especially as seen in adherent follicular lesions of favus. Sebaceous glands: Sebaceous glands are lipid secreting holocrine glands. Their maximum density is in seborrhoeic areas of the body, i.e. scalp, face, upper chest, etc. They get activated at puberty under the influence of androgen hormone. Seborrhoea: Abnormally copious secretion of sebum. Senear-Usher syndrome: Another name for pemphigus erythematosus. Sezary’s syndrome: A pruritic CTCL erythroderma associated with lymphadenopathy and the presence in the peripheral blood of more than 10% of atypical mononuclear cells (Sézary cells). Shagreen: A type of rough granular leather made from horses or asses skin. Shagreen patch seen over the back in tuberous sclerosis. Shingles: A term for herpes zoster Sister Joseph’s nodule: Umbilical metastasis from intra-abdominal neoplasm. Sjogren’s syndrome: A term for keratoconjunctivitis sicca and stoma often associated with rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. When occurring without these associated diseases, known as SICCA SYNDROME. Spirochaete: Any member of the family Spirochaetaceae, which includes the pathogens Treponema, Borrelia and Leptospira. Spongiosis: A process in which intercellular oedema fluid accumulates between the squamous cells of the epidermis. It occurs classically in acute and subacute dermatitis. Sporotrichosis: A fungal infection of man and animals, caused by Sporothrix schenckii. SSSS- Staphylococcal Scalded Skin Syndrome. Stevens-Johnson syndrome: A severe form of erythema multiforme with mucosal involvement. Strophulus: An outmoded term previously used either for papular urticaria. Sturge-Weber syndrome: Unilateral facial port-wine naevus with ipsilateral encephalomeningeal angiomatosis. Subcutaneous fat (Hypodermis): The subcutaneous fat layer is constituted by adipocytes. Adipocytes synthesize so much fat in their cytoplasm that lipid displaces the nucleus to the periphery of the cell.

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Essentials in Dermatology Subcutaneous fat act as shock absorber, facilitate mobility of skin over structures that underlie and acts as an insulator for heat. Syndrome: A set of symptoms occurring together or the sum of signs in a morbid process. Syphilis: Infection with Treponema pallidum. Tabes (dorsalis): A form of neurosyphilis; locomotor ataxia. TEN- Toxic Epidermal Necrolysis. Thrush: Term for infection of the oral, pharyngeal and vaginal mucosae with Candida albicans. Tinea: A fungal infection of skin, hair or nails caused by one of the dermatophytes Microsporum, Trichophyton or Epidermophyton, except for its use in terms tinea amiantacea and tinea versicolor (Latin tinea gnawing worm, moth). Trachoma: Infection of conjunctiva and cornea by Chlamydia trachomatis. Trichotillomania- a compulsion to pluck or twist out hair (Greek thrix, trichos hair, tillein to pluck, mania compulsion). Ulcer: A well-defined area of loss of skin and subcutaneous tissue involving the whole thickness of the skin and the underlying tissues, caused by infection, trauma or necrosis. Urticaria: An eruption of itching wheals, of physical, systemic or (less commonly) contact origin; nettle-rash, hives. Vagabond’s disease: A term for infestation with pediculosis corporis (French vagabond, from Latin vagabundus one who strolls around, from vagare to wander). Varicella: Disease caused by varicella-zoster virus; chicken-pox. Vegetans: Exuberant; vigorous skin lesions. Vellus: The short downy hair that replaces lanugo before or soon after birth on all hair-bearing areas except the scalp (Latin vellus wool, down, fleece). Venereal: Relating to or associated with sexual intercourse (Latin venereus from Venus, Veneris goddess of love). Verruca: Wart, excrescence; now used to denote viral wart, particularly of foot. Vesicle: A small blister less than 5 mm in diameter. Vitiligo: A primary loss of pigmentation from skin and hair, of unknown cause (Latin vitiligo a skin disease possibly from vitium flaw, blemish). Vulgaris: Common, ordinary. Wart (synonym verruca): This term used for any horny excrescence on the skin but properly so for lesions induced by the papovavirus. Weal (wheal): A transient circumscribed oedematous swelling as seen in urticaria or dermographism. Whitfield’s ointment: 6% benzoic acid compounded with 3% salicylic acid as ointment. Whitlow: Acute paronychia or purulent infection (abscess) of distal finger pulp; felon. Also, specifically, herpetic or melanotic whitlow. Wickham’s striae: A characteristic pattern of white streaking seen on papules of lichen planus.

Terminology in Dermatology, Sexually Transmitted Diseases and Leprosy Wood’s light: A source of ultraviolet radiation from which most visible rays have been excluded by the use of a filter. This photoemission causes fluorescence in certain skin conditions, especially in some fungal infections (Tinea capitis, tinea versicolor) and porphyrins. Xanthelasma: Symmetrical yellow plaques of eyelids due to lipid deposition. Yeast: Term used generically for any of a group of saprophytic unicellular fungi e.g.,C. albicans. Zoster: A shortened term for herpes zoster.

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Answers

Answers

Set I (1-400) 1.B 11.B 21.A 31.A 41.B 51.A 61.B 71.A 81.B 91.A 101.C 111.A 121.C 131.A 141.D 151.D 161.D 171.C 181.B 191.B 201.C 211.D 221.C 231.B 241.C 251.A 261.D 271.C 281.D 291.A 301.B

2.A 12.C 22.D 32.A 42.D 52.B 62.A 72.C 82.C 92.D 102.A 112.A 122.C 132.C 142.D 152.C 162.C 172.A 182.B 192.C 202.C 212.A 222.A 232.D 242.B 252.C 262.D 272.D 282.B 292.D 302.C

3.A 13.B 23.B 33.A 43.A 53.A 63.B 73.B 83.D 93.D 103.B 113.C 123.D 133.A 143.B 153.B 163.A 173.A 183.C 193.A 203.D 213.D 223.A 233.B 243.D 253.B 263.C 273.D 283.A 293.D 303.A

4.C 14.D 24.A 34.C 44.B 54.A 64.B 74.C 84.A 94.A 104.A 114.A 124.C 134.D 144.A 154.B 164.C 174.D 184.C 194.C 204.D 214.C 224.A 234.D 244.A 254.B 264.A 274.D 284.D 294.B 304.C

5.A 15.C 25.A 35.C 45.B 55.B 65.A 75.B 85.D 95.D 105.C 115.D 125.A 135.C 145.A 155.D 165.A 175.B 185.A 195.A 205.B 215.B 225.D 235.A 245.B 255.B 265.D 275.D 285.B 295.A 305.C

6.B 16.A 26.A 36.C 46.B 56.A 66.B 76.C 86.A 96.D 106.D 116.C 126.D 136.B 146.D 156.B 166.B 176.D 186.D 196.C 206.D 216.A 226.D 236.B 246.A 256.A 266.C 276.A 286.A 296.A 306.A

7.A 17.B 27.C 37.A 47.B 57.B 67.A 77.B 87.D 97.C 107.C 117.A 127.A 137.A 147.B 157.D 167.A 177.C 187.B 197.A 207.C 217.C 227.C 237.B 247.B 257.D 267.D 277.C 287.A 297.D 307.A

8.C 18.D 28.B 38.C 48.A 58.B 68.D 78.A 88.A 98.A 108.A 118.D 128.A 138.A 148.B 158.D 168.D 178.A 188.A 198.D 208.B 218.C 228.B 238.C 248.B 258.D 268.A 278.C 288.A 298.C 308.D

9.A 19.D 29.C 39.A 49.A 59.B 69.B 79.C 89.B 99.C 109.A 119.A 129.B 139.D 149.D 159.C 169.A 179.C 189.C 199.B 209.D 219.D 229.B 239.B 249.C 259.B 269.B 279.D 289.D 299.C 309.C

10.B 20.A 30.D 40.B 50.A 60.C 70.A 80.A 90.B 100.A 110.D 120.D 130.C 140.A 150.A 160.C 170.D 180.B 190.D 200.A 210.A 220.A 230.D 240.A 250.D 260.B 270.B 280.C 290.A 300.D 310.D Contd...

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Essentials in Dermatology Contd... 311.A 321.A 331.A 341.A 351.C 361.D 371.B 381.A 391.A

312.B 322.D 332.A 342.C 352.A 362.A 372.C 382.B 392.A

313.A 323.C 333.C 343.A 353.D 363.C 373.B 383.A 393.A

314.A 324.A 334.D 344.A 354.D 364.A 374.D 384.A 394.A

315.B 325.C 335.D 345.D 355.A 365.C 375.D 385.A 395.A

316.D 326.A 336.A 346.A 356.A 366.B 376.A 386.A 396.B

317.A 327.D 337.D 347.A 357.A 367.B 377.B 387.B 397.C

318.B 328.A 338.C 348.A 358.C 368.A 378.B 388.A 398.C

319.A 329.A 339.C 349.D 359.B 369.D 379.A 389.A 399.D

320.D 330.B 340.C 350.A 360.C 370.A 380.A 390.D 400.A

7. C 15. C 23. B 31. B 39. A 47. D 55. C 63. A 71. B 79. D 87. B 95. D 103. C 111. B 119. A 127. A 135. B 143. A 151. D 159. C 167. C 175. B 183. B 191. B 199. A 207. D 215. A 223. C 231. C 239. D

8. D 16. A 24. A 32. A 40. B 48. B 56. B 64. D 72. B 80. B 88. B 96. A 104. A 112. C 120. B 128. A 136. D 144. C 152. C 160. B 168. B 176. C 184. B 192. C 200. B 208. B 216. D 224. B 232. B 240. D

Key to Set II (1-245) 1. B 9. D 17. D 25. C 33. B 41. B 49. A 57. D 65. A 73. B 81. C 89. A 97. D 105. D 113. C 121. D 129. C 137. A 145. D 153. A 161. D 169. C 177. C 185. A 193. D 201. B 209. B 217. C 225. D 233. D 241. B

2. B 10. C 18. A 26. D 34. C 42. A 50.C 58. A 66. A 74. A 82. A 90. A 98. D 106. D 114. A 122. A 130. A 138. D 146. B 154. C 162. C 170. A 178. A 186. A 194. A 202. A 210. C 218. B 226. B 234. B 242. D

3. C 11. A 19. C 27. B 35. A 43. D 51. B 59. B 67. B 75. C 83. B 91. C 99. B 107. C 115. C 123. B 131. B 139. D 147. A 155. A 163. A 171. D 179. B 187. A 195. A 203. A 211. A 219. C 227. C 235. C 243. A

4. D 12. D 20. A 28. D 36. C 44. D 52. D 60. C 68. D 76. C 84. D 92. B 100. A 108. B 116. B 124. D 132. D 140. A 148. D 156. D 164. D 172. A 180. D 188. C 196. C 204. D 212. D 220. A 228. D 236. C 244. B

5. D 13. B 21. B 29. D 37. A 45. C 53. A 61. C 69. A 77. A 85. D 93. B 101. C 109. A 117. C 125. D 133. B 141. A 149. A 157. B 165. A 173. A 181. D 189. B 197. A 205. B 213. B 221. B 229. D 237. B 245. B

6. A 14. A 22. B 30. A 38. C 46. A 54. D 62. B 70. C 78. D 86. A 94. A 102. B 110. D 118. B 126. B 134. A 142. B 150. D 158. C 166. C 174. A 182. A 190. D 198. A 206. A 214. C 222. C 230. A 238. A

Answers Key to MCQs in Dermatology- Basic Sciences (1-55) 1.B 5.A 9.B 13.A 17.D 21.A 25.C 29.D 33.D 37.C 41.D 45.D 49.A 53.C

2.C 6.A 10.B 14.B 18.D 22.C 26.D 30.D 34.D 38.D 42.B 46.B 50.A 54.A

3.B 7.C 11.D 15.B 19.C 23.A 27B 31.D 35.D 39.D 43.C 47.C 51.A 55.C

4.A 8.D 12.B 16.C 20.C 24.A 28.D 32.D 36.D 40.A 44.C 48.A 52.A

Key to MCQs in Clinical Dermatology-Part 1 (1-110) 1. A 9. A 17. A 25. D 33. D 41. B 49. B 57. A 65. C 73. B 81. A 89. C 97. D 105. C

2. C 10. C 18. C 26. C 34. C 42. B 50. A 58. D 66. D 74. C 82. B 90. A 98. A 106. B

3. A 11. C 19. C 27. A 35. C 43. D 51. C 59. B 67. A 75. D 83. B 91. C 99. C 107. B

4. C 12. D 20. C 28. C 36. A 44. C 52. B 60. B 68. A 76. D 84. B 92. B 100. D 108. A

5. C 13. C 21. D 29. A 37. B 45. A 53. C 61. A 69. B 77. D 85. B 93. B 101. D 109. C

6. C 14. A 22. B 30. B 38. A 46. A 54. B 62. D 70. D 78. B 86. A 94. D 102. D 110. C

7. B 15. A 23. A 31. A 39. A 47. C 55. B 63. D 71. C 79. B 87. B 95. C 103. B

8. B 16. A 24. C 32. D 40. B 48. C 56. C 64. D 72. A 80. B 88. D 96. D 104. B

7. A 15. B 23. A 31. D 39. D 47. A 55. A 63. A 71. A 79. C 87. A 95. A

8. A 16. B 24. A 32. A 40. C 48. D 56. A 64. A 72. A 80. B 88. A 96. C

Key to MCQs in Clinical Dermatology- Part II (1-99) 1. B 9. B 17. D 25. D 33. A 41. A 49. A 57. B 65. B 73. B 81. A 89. C 97. C

2. C 10. B 18. B 26. A 34. D 42. A 50. C 58. A 66. D 74. A 82. B 90. A 98. B

3. A 11. A 19. A 27. D 35. D 43. C 51. B 59. A 67. A 75. A 83. A 91. B 99. D

4. A 12. D 20. A 28. A 36. A 44. A 52. A 60. A 68. A 76. A 84. C 92. A

5. D 13. A 21. A 29. B 37. A 45. A 53. C 61. A 69. C 77. A 85. B 93. A

6. D 14. A 22. A 30. A 38. B 46. A 54. B 62. A 70. D 78. A 86. B 94. A

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Essentials in Dermatology Key to MCQs in Sexually Transmitted Diseases (1-130) 1. B 9. A 17. C 25. B 33. D 41. C 49. A 57. A 65. B 73. C 81. C 89. A 97. A 105. D 113. C 121. C 129. C

2. D 10. A 18. A 26. B 34. D 42. D 50. D 58. C 66. A 74. A 82. A 90. C 98. A 106. B 114. A 122. D 130. D

3. D 11. D 19. B 27. C 35. B 43. C 51. A 59. D 67. B 75. B 83. D 91. A 99. B 107. D 115. A 123. A

4. D 12. B 20. D 28. A 36. A 44. C 52. D 60. B 68. A 76. A 84. B 92. C 100. C 108. C 116. A 124. B

5. C 13. A 21. B 29. A 37. D 45. B 53. C 61. C 69. B 77. D 85. C 93. B 101. D 109. D 117. C 125. A

6. D 14. D 22. B 30. C 38. B 46. D 54. A 62. A 70. B 78. D 86. D 94. B 102. A 110. B 118. D 126. A

7. D 15. B 23. A 31. B 39. D 47. D 55. D 63. A 71. A 79. D 87. C 95. C 103. D 111. B 119. B 127. B

8. C 16. C 24. C 32. D 40. C 48. D 56. C 64. D 72. D 80. D 88. B 96. C 104. C 112. D 120. C 128. A

6. A 14. C 22. A 30. D 38. A 46. A 54. A 62. A 70. B 78. C 86. B 94. D

7. D 15. C 23. B 31. B 39. D 47. A 55. D 63. B 71. C 79. B 87. B 95. A

8. C 16. D 24. B 32. B 40. C 48. D 56. A 64. D 72. C 80. C 88. B

Key to MCQs in Leprosy (1-95) 1. B 9. A 17. A 25. C 33. D 41. C 49. A 57. D 65. D 73. B 81. C 89. A

2. D 10. B 18. C 26. B 34. A 42. A 50. D 58. B 66. B 74. A 82. B 90. D

3. A 11. B 19. C 27. A 35. A 43. C 51. C 59. D 67. C 75. B 83. A 91. A

4. A 12. B 20. D 28. C 36. D 44. A 52. D 60. A 68. A 76. C 84. A 92. A

5. D 13. A 21. B 29. D 37. A 45. D 53. A 61. B 69. A 77. C 85. A 93. C