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  • 1. Essentials in Dermatology (with Multiple Choice Questions)
  • 2. Essentials in Dermatology (with Multiple Choice Questions) 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 JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi • Ahmedabad • Bengaluru • Chennai • Hyderabad • Kochi Kolkata • Lucknow • Mumbai • Nagpur • St Louis (USA) ® Second Edition
  • 3. Published by Jitendar P Vij Jaypee Brothers Medical Publishers (P) Ltd Corporate Office 4838/24, Ansari Road, Daryaganj, New Delhi 110 002, India Phone: +91-11-43574357 Registered Office B-3, EMCA House, 23/23B Ansari Road, Daryaganj, New Delhi 110 002, India Phones: +91-11-23272143, +91-11-23272703, +91-11-23282021, +91-11-23245672 Rel: +91-11-32558559 Fax: +91-11-23276490, +91-11-23245683 e-mail: Visit our website: Branches • 2/B, Akruti Society, Jodhpur Gam Road Satellite Ahmedabad 380 015 Phones: +91-79-26926233, Rel: +91-79-32988717 Fax: +91-79-26927094 e-mail: • 202 Batavia Chambers, 8 Kumara Krupa Road, Kumara Park East Bengaluru 560 001 Phones: +91-80-22285971, +91-80-22382956, +91-80-22372664 Rel: +91-80-32714073 Fax: +91-80-22281761 e-mail: • 282 IIIrd Floor, Khaleel Shirazi Estate, Fountain Plaza, Pantheon Road Chennai 600 008 Phones: +91-44-28193265, +91-44-28194897, Rel: +91-44-32972089 Fax: +91-44-28193231 e-mail: • 4-2-1067/1-3, 1st Floor, Balaji Building, Ramkote Cross Road Hyderabad 500 095 Phones: +91-40-66610020, +91-40-24758498 Rel:+91-40-32940929 Fax:+91-40-24758499, e-mail: • No. 41/3098, B & B1, Kuruvi Building, St. Vincent Road Kochi 682 018, Kerala Phones: +91-484-4036109, +91-484-2395739, +91-484-2395740 e-mail: • 1-A Indian Mirror Street, Wellington Square Kolkata 700 013 Phones: +91-33-22651926, +91-33-22276404, +91-33-22276415 Rel: +91-33-32901926 Fax: +91-33-22656075, e-mail: • Lekhraj Market III, B-2, Sector-4, Faizabad Road, Indira Nagar Lucknow 226 016 Phones: +91-522-3040553, +91-522-3040554 e-mail: • 106 Amit Industrial Estate, 61 Dr SS Rao Road, Near MGM Hospital, Parel Mumbai 400012 Phones: +91-22-24124863, +91-22-24104532, Rel: +91-22-32926896 Fax: +91-22-24160828, e-mail: • “KAMALPUSHPA” 38, Reshimbag, Opp. Mohota Science College, Umred Road Nagpur 440 009 (MS) Phone: Rel: +91-712-3245220, Fax: +91-712-2704275 e-mail: USA Office 1745, Pheasant Run Drive, Maryland Heights (Missouri), MO 63043, USA Ph: 001-636-6279734 e-mail:, 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
  • 4. 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 Second Edition
  • 5. 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 Preface to the First Edition
  • 6. 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 Acknowledgements
  • 7. Essentials in Dermatologyx • 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
  • 8. “…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. Reviews
  • 9. 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 Contents
  • 10. Essentials in Dermatologyxiv 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
  • 11. Ten Most Influential People in Medicine and Dermatology 3 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. 1 Ten Most Influential People in Medicine and Dermatology 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.
  • 12. Essentials in Dermatology4 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.
  • 13. History of Dermatology in the World 5 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 well- advanced, 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 2 History of Dermatology in the World dermatologists of the following century were able to build. • Despite developments in 19th century- vaccination 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 (1816- 1880) 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; communi- cations–books, photography, radio, films, television, computers; transport), general scientific developments (genetics- structure
  • 14. Essentials in Dermatology6 of DNA; inflammation-histamine, prostag- landins, cytokines, adhesion molecules; immunology-cell mediated and humoral immunity; tissue culture; pathogenic agents- spirochetes, viruses, prion; therapies- x-rays, antibacterial, immunosuppressive; con- trolled clinical trials), and strictly dermatological areas(books- Jadassohn, Pillsbury, Rothman, Rook; biology- keratinocyte, melanocyte, Langerhans cell, basement membrane; diseases- epidermo- lysis bullosa, pemphigus, toxic epidermal necrolysis; people- from Unna to Katz; therapies- local steroids, griseofulvin, phototherapy, retinoids, Moh’s surgery, laser, cryotherapy). 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 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
  • 15. History of Dermatology in the World 7 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 full- fledged 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.
  • 16. Essentials in Dermatology8 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. 3 Microanatomy of the Skin 5. Vitamin D formation: Vitamin D3 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 keratino- cytes. 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 stages- specification, morphogenesis and differentiation. Its specification occurs from 0 to 60 days, morphogenesis from 2 to 5 months, and differentiation from 5 to 9 months.
  • 17. Microanatomy of the Skin 9 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
  • 18. Essentials in Dermatology10 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 approxi- mately 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 upper- papillary dermis that interdigitates between the rete ridges and the deeper-reticular dermis recognized by the thicker, aggregated bundles of collagen.
  • 19. Microanatomy of the Skin 11 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.
  • 20. Essentials in Dermatology12 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.
  • 21. Physiology, Biochemistry and Immunology of the Skin 13 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. 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 4 Physiology, Biochemistry and Immunology of the Skin 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. 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
  • 22. Essentials in Dermatology14 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 inflam- matory 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 37o C 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
  • 23. Physiology, Biochemistry and Immunology of the Skin 15 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 micro- organisms. 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. Hyper- sensitivity 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.
  • 24. Essentials in Dermatology16 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 precon- ceived 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... PRELIMINARY GENERAL HISTORY Biodata: Age, sex, income, occupation, address, marital status. Principles of Diagnosis in Dermatology 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. 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. Treatment history: Skin lesions are often self- manipulated by home remedies, or over the 5
  • 25. Principles of Diagnosis in Dermatology 17 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.
  • 26. Essentials in Dermatology18 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 collection- Vesicle, 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 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- 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, umbi- licated, pedunculated, etc. Fig. 5.1: Macule—depigmented flat lesions of variable size and shape of vitiligo vulgaris and lip tip type Fig. 5.2: Papule—solid elevated lesions of verruca vulgaris of less than 0.5 cm
  • 27. Principles of Diagnosis in Dermatology 19 Fig. 5.3: Papule—dome shaped papule, a few of them umbilicated of molluscum contagiosum Fig. 5.4: Typical umbilicated papule of molluscum contagiosum Fig. 5.5 Violaceous colored papules of lichen planus over the genitalia and thigh • 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. • Vesiclesandbullae:Vesicleandbullaearetwo 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. Fig. 5.6: Plaque—flat elevated lesions covered with silvery white micaceous scales of psoriasis vulgaris
  • 28. Essentials in Dermatology20 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. 5.12: Large tense bulla of bullous pemphigoid on an erythematous base Fig. 5.11: Bulla—small blisters on erythematous bases of bullous pemphigoid
  • 29. Principles of Diagnosis in Dermatology 21 Fig. 5.13: Pustule—numerous tiny pus filled lesions on erythematous background in a case of pustular psoriasis • 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 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
  • 30. Essentials in Dermatology22 • 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 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
  • 31. Principles of Diagnosis in Dermatology 23 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 (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 charac- teristic 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
  • 32. Essentials in Dermatology24 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 DISTRIBUTION OF SKIN LESIONS IN SOME DERMATOLOGICAL DISORDERS Disease Classical sites of involvement 1. Acne vulgaris Face, upper trunk, proximal parts of upper extremities 2. Atopic dermatitis Infants -face and extensor aspects of limbs (Figs 5.20A and B) Children and adults-flexures (Figs 5.21A and B). 3. Dermatitis herpetiformis Scalp, extensor aspects of limbs, shoulder and buttocks (Figs 5.22A and B). 4. Lichen planus Flexor aspect of upper extremities (wrists), trunk (lumbosacral area), shins, glans penis (Figs 5.23A and B). 5. Neurodermatitis Nape of neck, wrist, ankle, genitalia, and perianal area (Figs 5.24A and B). 6. Pityriasis rosea Herald patch-trunk. Daughter patches-Christmas tree pattern over the trunk (Figs 5.25A and B). 7. Psoriasis vulgaris Extensor aspects of limbs, scalp, lumbosacral area (Figs 5.26A and B). 8. Scabies 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). 9. Seborrhoeic dermatitis 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). 10. Tinea versicolor Upper trunk (Figs 5.31A and B).
  • 33. Principles of Diagnosis in Dermatology 25 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
  • 34. Essentials in Dermatology26 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. • 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 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.
  • 35. Principles of Diagnosis in Dermatology 27 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 hista- mine 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-
  • 36. Essentials in Dermatology28 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 nonblanchable- raised 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. 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 dermato- fibroma 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.
  • 37. Principles of Diagnosis in Dermatology 29 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—Micros- porum 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 in- fection (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 micros- copy, 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.
  • 38. Essentials in Dermatology30 12. VDRL 13. HIV antibody detection test 14. Culture and sensitivity test 15. Patch testing 16. Prick testing 17. Intradermal testing 18. LE cell phenomenon 19. Mouse foot pad inoculation 20. Immunofluorescence 21. Hair examination and counts 22. 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.
  • 39. Bacterial Infections 31 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 pyodermasandsecondarypyodermas(Table6.1). 6 Bacterial Infections 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 Secondary pyodermas 1. Invasion of normal skin by bacteria 1. Develop in areas of already damaged/compromised skin 2. Single species of bacteria involved 2. Mixture of organisms involved 3. Appearance of lesions is characteristic 3. Not characteristic e.g., impetigo, erysipelas, furuncle 4. Treatment is clear cut – Drugs aimed 4. Role of antibacterial treatment less defined. at the microorganism Here, the aim is to treat the underlying process
  • 40. Essentials in Dermatology32 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 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 • 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- charac- terized by crusted ulcers (not erosions). Bullous Impetigo • 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. 6.1: Impetigo contagiosa–honey colored crusted lesions over the face of a child Fig. 6.2: Bullous impetigo–large pus filled blisters over the trunk of a child
  • 41. Bacterial Infections 33 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). 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. 6.3: Ecthyma–crusted lesion over the leg with ulcerated lesions Fig. 6.4: Sycosis barbae– grouped follicular based crusted lesions in the beard area of the face
  • 42. Essentials in Dermatology34 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 demon- strated 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, particularly in regions subject to friction, occlusion, and perspiration. Differential diagnosis: Folliculitis- Inflammatory change is confined within the follicle without any surrounding inflam- mation – 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 under- lying diabetes mellitus, alcoholism, malnu- trition, blood dyscrasias, iatrogenic or other immunosuppression including HIV infection. Fever, malaise, prostration accompany. Differential diagnosis: Anthrax – charac- terized by painless, hemorrhagic crusted (blackish eschar) lesion with surrounding gelatinous edema out of proportion to the extent of the lesion. Fig. 6.5: Lupoid sycosis–scarring alopecia in the beard area showing active pustular lesions at the periphery Fig. 6.6: Furuncle–a red tender suppurated nodule in a case of erythroderma
  • 43. Bacterial Infections 35 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 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. 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 38.9o C or higher 2. Erythematous eruption 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) TEN 1. Age – less than 5 years 1. More than 40 years 2. Skin shows marked tenderness 2. Mild to moderate tenderness 3. Distribution – face, neck , axilla, groin 3. No clear distribution 4. Mucoca – not involved 4. Involved 5. Prognosis – good 5. Poor 6. Histology – subgranular split due to acantholysis 6. Necrosis of epidermis Fig. 6.7 Fig. 6.8
  • 44. Essentials in Dermatology36 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 mens- truation; 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 well- preserved. 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. 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 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. Fig. 6.9: Cellulitis–lower leg showing shiny erythema and edema
  • 45. Bacterial Infections 37 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. Necrotizing Fasciitis (Streptococcal gangrene) • It represents cellulitis that has progressed to gangrene of subcutaneous tissue followed by necrosis of overlying skin (Fig. 6.10). • It is not only caused by group A streptococci but also due to other bacterial species (mixture of anaerobes/facultative orga- nisms). 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 exami- nation 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. Fig. 6.10: Necrotizing fascitis—cellulitis progressing to gangrene over the leg
  • 46. Essentials in Dermatology38 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 minutis- simum, 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 predo- minantly affects upper trunk, individual lesions are small, but not erythematous and satellite lesions are more commonly seen than 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 white- yellow (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. Fig. 6.11: Erythrasma–asymptomatic brownish macular lesion with fine scaling in the axilla
  • 47. Bacterial Infections 39 • 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. 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 Pitted Keratolysis • Causative agent- Corynebacterium species, Streptomyces species, Dermatophilus congo- lensis 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 Fig. 6.14: Pitted keratolysis–soles demonstrating multiple pits
  • 48. Essentials in Dermatology40 Fig. 6.15: Botryomycosis–swelling of the foot with multiple nodules over it form granules - mycetoma and actino- mycosis, 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 trimethoprim- sulfamethoxazole, minocycline, erythro- mycin 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
  • 49. Bacterial Infections 41 • 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. 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). 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 Fig. 6.17 Fig. 6.18
  • 50. Essentials in Dermatology42 • 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. Fig. 6.19: Anthrax–"Box car" arrangement of bacillus anthracis in gram's stained smear Ciprofloxacin, erythromycin, tetracycline and chloramphenicol are alternative drugs for penicillin sensitive patients. 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.
  • 51. Viral Infections 43 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 7 Viral Infections 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 auto- inoculation (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 child- hood 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
  • 52. Essentials in Dermatology44 “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 more common on the face and neck (Figs 7.5 and 7.6). Diagnosis • It is made clinically when necessary, histological examination is diagnostic. 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 Fig. 7.4: Molluscum contagiosum—lesions over the gluteal area and thigh in a child
  • 53. Viral Infections 45 • 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). 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. 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 • Oral cimetidine or intravenous cidofovir can be used in widespread lesions. HUMAN PAPILLOMAVIRUS INFECTION (WARTS) • 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 mucocut- aneous 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 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
  • 54. Essentials in Dermatology46 papillomas and epidermodysplasia verruci- formis. 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. 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. • 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 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
  • 55. Viral Infections 47 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 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. 7.9: Genital warts—cauliflower like lesion of condyloma acuminata over the glans penis along with herpes genitalis Fig. 7.10: Buschke Lowenstein tumor—a large verrucous growth seen involving the glans penis
  • 56. Essentials in Dermatology48 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. 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. • 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 immuno- modulators (Interferon, especially interferon 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
  • 57. Viral Infections 49 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. • 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. Fig. 7.13: Primary herpetic gingivostomatitis—lips also involved along with oral cavity with vesiculation, erosions and hemorrhagic crusting
  • 58. Essentials in Dermatology50 • 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. 7.14: 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 Fig. 7.16: Herpetic whitlow—grouped vesicles over the great toe
  • 59. Viral Infections 51 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. Clinical Entities Caused by HSV-2 1. Genital herpes 2. Recurrent lumbosacral herpes simplex 3. HSV infections in the newborn. Fig. 7.17: Eczema herpeticum—widespread vesicular eruption over the face in a patient with allergic contact dermatitis Diagnosis • 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 multi- nucleated 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. Primary Infection Herpetic gingivo-stomatitis— • Acyclovir 5 mg/kg body weight 8 hourly for 7 to 10 days. Fig. 7.18: Tzanck smear showing multinucleated giant cell
  • 60. Essentials in Dermatology52 • Others like eczema herpeticum and disseminated herpes need to be treated energetically on similar lines. • Herpetic whitlow and keratoconjunctivitis may be treated with oral acyclovir 200 mg 5 times a day for 7 to 10 days. 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 phos- phorylated 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. 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 the sensory neurons following an earlier varicella attack. • Both conditions are usually benign and self- limiting in patients with normal immuno- logical 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 dissemi- nated cutaneous disease and systemic involvement, usually pneumonia, hepatitis, or encephalitis. Fig. 7.19: Chicken pox—vesicular eruption over the trunk in different stages of evolution in an adult patient
  • 61. Viral Infections 53 • 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 usually by staphylococci or streptococci and may be prolonged by scarring. Other notable complications are primary varicella pneu- monia, 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, chorio- retinitis and cortical atrophy. 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. 20: Chicken pox—dew drops on rose petals appearance Fig. 7. 21: Herpes zoster—grouped vesicles on erythematous patches in thoracic dermatome
  • 62. Essentials in Dermatology54 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
  • 63. Viral Infections 55 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, multi- dermatomal (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. Fig. 7.24: Herpes zoster—zoster occurring in multiple dermatomes • 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. 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, immuno- suppressed 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.
  • 64. Essentials in Dermatology56 • 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) • It is a special form of widespread cutaneous viral infection occurring in a patient with pre- existing 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 gamma- globulin.
  • 65. Fungal Infections 57 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 manufacturechlorophyll.Withoutphotosynthetic capabilities,theyaredependentonotherlifeforms 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 8 Fungal Infections • 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
  • 66. Essentials in Dermatology58 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 notreachtheedgeoftheerythematousborder, this acute eruption, has self limited course). Tineacruris-ringwormofthegroin(“jock’sitch” “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, erythe- matous plaques with satellite pustules and it more often involves the scrotum), inverse psoriasis (tends to be asymptomatic, well- defined erythematous plaque), and eryth- rasma (lacks a scaling border and inflammation, asymptomatic in nature, fluoresces coral red under a wood light). Fig. 8.1: Tinea corporis–typical annular erythematous ring like lesions of tinea corporis 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
  • 67. Fungal Infections 59 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. Inthewesternliterature,commonestcausative organismrecordedisT.tonsurans.Bothofthem 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. 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 Fig. 8.4: Tinea faciei–erythematous scaly annular lesion over the face 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
  • 68. Essentials in Dermatology60 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) Tineapedis-ringwormofthefeet(“Athletefoot”) • Interdigital type-interdigital scaling and maceration with fissures is the most common form (Fig. 8.8). • Chronic hyperkeratotic type or Moccasin foot- widespread 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). Thehyperkeratotictypemustbedifferentiated from palmoplantar psoriasis, palmoplantar keratodermasandhyperkeratoticeczema.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 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 hyper- keratotic eczema must be considered as differential diagnosis. Tinea unguium- fungal infections of the nails • Nailinfectionstartsatthefreemarginorlateral borders of the nails, as yellow discoloration and progress proximally (distal and lateral subungual onychomycosis). 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
  • 69. Fungal Infections 61 • 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 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). Diagnosis • KOH mount– definitive diagnosis is made by the microscopic examination and identi- fication 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 Fig. 8.9: Tinea manuum–unilateral scaly lesions of the palm Fig. 8.10: Tinea manuum with tinea unguium Fig. 8.11: Tinea unguium–thickening and dystrophy of involved nails
  • 70. Essentials in Dermatology62 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) 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%) Duration of therapy is 4 to 6 weeks or 2 weeks more after clearance of lesions. • Systemictherapy–requiredincaseofhairand 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). Fig. 8.13: KOH mount–showing branching septate hyphae 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
  • 71. Fungal Infections 63 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 propensitytopresentaseitherhypopigmented 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 hyperactive melanocytes. The hyperpig- mentation 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). Fig. 8.15: Tinea versicolor–hypopigmented macules with fine powdery scales Fig. 8.16: Tinea versicolor–hyperpigmented macules with fine scaling
  • 72. Essentials in Dermatology64 • 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. 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 versi- color 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. 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 Fig. 8.19: Parker ink staining of hyphae and spores of tinea versicolor
  • 73. Fungal Infections 65 CANDIDIASIS – Causative agent–Candida albicans. This yeast like fungus is normally found on the mucous membranes, skin, in the gastro- intestinal 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, immunocom- promised state including HIV infection. 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.Itisthemostcommonformoforal candidiasis. Other forms of oral candidias is include acute and chronic atrophic candidiasis, chronic hyperplastic candidiasis, and median rhomboid glossitis. Oral thrush can be confused with coated tongue due to dehydration, mucositis due to chemo- therapeutic drugs, aphthous ulcerations, herpetic infections, oral hairy leukoplakia, erythema multiforme, pemphigus, lichen planus, discoid lupus erythematosus, Pernicious anemia, histoplasmosis, leuko- plakia, 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 Fig. 8.20: Oral candidiasis–curdy white deposits on the hard palate in a baby Fig. 8.21: Oral candidiasis with angular cheilitis in a HIV adult case Fig. 8.22: Intertriginous candidiasis–toe cleft showing moist macerated lesion
  • 74. Essentials in Dermatology66 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 balano- posthitis occurs as a counter part in males (Fig. 8.25). 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. 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 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 Fig. 8.25: Candidal balanoposthitis–glazed erythema with pustulation over glans and prepuce
  • 75. Fungal Infections 67 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. hypothyro- idism, 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. TINEA NIGRA • 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. 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 MYCETOMA • 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 Madurella mycetomatis Exophila jeanselmei Pyrenochaeta romeroi Fusarium species Actinomycetoma Actinomadura madurae Nocardia brasilensis Actinomadura pelletieri
  • 76. Essentials in Dermatology68 • 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. • 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 Actino- myces 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 sulfamethoxazole- trimethoprim 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) • 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- Fig. 8.26: Mycetoma–a triad of features – swelling, discharging sinuses and discharge containing granules seen commonly over the foot Fig. 8.27: Mycetoma over the upper back
  • 77. Fungal Infections 69 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 leish- maniasis (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(amphotericinB,5-fluorocytosine, triazole derivatives especially itraconazole, and thiabendazole). RHINOSPORIDIOSIS • Rhinosporidiosis is a chronic granulomatous mycosis caused by Rhinosporidium seeberi. • 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 bleedingarethemostcommonsymptoms.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. 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
  • 78. Essentials in Dermatology70 • 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 conidio- bolomycosis (etiological agent: Conidiobolus Fig. 8.30: Rhinosporidiosis–pink friable polypoidal growth over the root of the nose Fig. 8.31: Rhinosporidiosis–noduloplaque lesions over the arms 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. Fig. 8.32: Subcutaneous phycomycosis–shiny disk like indurated lesion over the thigh, can be insinuated at the margin with fingers
  • 79. Fungal Infections 71 • 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 immuno- compromised. • 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),althoughnecroticpapules,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.
  • 80. Essentials in Dermatology72 9 Infestations SCABIES (THE ITCH, SEVEN YEAR ITCH) • 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 40- 50 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
  • 81. Infestations 73 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. 9.4: Scabies – typical finger web spaces involvement with papular, vesicular and crusted lesions Fig. 9.5: Scabies – periumbilical papular lesions Fig. 9.6: Scabies – genital and thigh area involved by papular and excoriated lesions Fig. 9.7: Scabies – papular lesions over the gluteal area Fig. 9.3: An egg of sarcoptes
  • 82. Essentials in Dermatology74 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. • 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 glomeru- lonephritis particularly in tropics. Fig. 9.8: Scabies—typical burrows of scabies of the shaft of the penis 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
  • 83. Infestations 75 • 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. Fig. 9.11: Nodular scabies—nodules seen over the scrotum
  • 84. Essentials in Dermatology76 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 immuno- suppressive 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 neuro- dermatitis (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. ANIMAL SCABIES • Contracted from pet animals-cats, dogs, or birds. • No burrows seen, only itching and papulo- vesicular 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. 9.12: 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 Fig. 9.14: Pediculus humanus capitis
  • 85. Infestations 77 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 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 charac- teristic 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. 9.15: Phthirus pubis Fig. 9.16: Nits attached to the hair Fig. 9.17: Pediculosis capitis – nits on the hair
  • 86. Essentials in Dermatology78 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. 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. 9.18: Plica polonica—matting of the scalp hair • 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 lympha- denopathy-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. Fig. 9.19: Phthriasis pubis – adult louse clung to the hair
  • 87. Infestations 79 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 palpe- brarum) (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. PAPULAR URTICARIA • Papular urticaria occurs as episodic, symmetrically distributed, pruritic, urticarial papules that are caused by bites 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 • 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, Fig. 9.21: Larva migrans eruption – serpentine erythematous tract of larva migrans over the thigh of a child
  • 88. Essentials in Dermatology80 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 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. Fig. 9.22: Myiasis—maggots in chromomycosis lesion on the hand
  • 89. Infestations 81 • Old world type—Cutaneous leishmaniasis. • New world type—Mucocutaneous leish- maniasis. • 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 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 anti- moniate, C. Systemic therapy: Antimonials—Sodium stibogluconate or meglumine antimoniate 20 mg/kg/day for 14-21 days. Penta- midine isethionate- 4 mg salt / kg – weekly doses may be used. D. Other drugs: Amphotericin B, keto- conazole, itraconazole, dapsone, rifampicin, etc. Fig. 9.23: Cutaneous leishmaniasis— noduloulcerative lesion over the forearm
  • 90. Essentials in Dermatology82 10 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.
  • 91. Papulosquamous Disorders 83 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. 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 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 Fig. 10.1: Psoriasis vulgaris–plaque lesions over the extensor surface of limbs and trunk Fig. 10.2: Psoriasis vulgaris–plaque lesions over the trunk Fig. 10.3: Flexural psoriasis–psoriatic plaque involving axilla
  • 92. Essentials in Dermatology84 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 lumbo- sacral region are commonly involved. • Lesions of active psoriasis often appear in areas of epidermal injury-Koebner pheno- menon. • 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. • 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. 10.4: Psoriasis vulgaris–lesions extending beyond hair line Fig. 10.5: Psoriasis vulgaris–nail pitting
  • 93. Papulosquamous Disorders 85 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 type- acute exanthematic type (Fig. 10.7) or generalized pustular psoriasis of pregnancy- Impetigo 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, 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. 10.6: Psoriatic arthritis—characteristically involving distal interphalangeal joint leading to swan neck deformity Fig. 10.7: Generalized pustular psoriasis- generalized pustular eruption in a child Fig. 10.8: Acrodermatitis continua—nail dystrophy and finger tip involved by pustular psoriasis
  • 94. Essentials in Dermatology86 • 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 micro- abscesses. 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 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, condy- loma lata, positive serological test for syphilis.
  • 95. Papulosquamous Disorders 87 • 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 steroids- Topical 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 generally not recommended due to the well- known risk of rebound and pustular conversion. • Vitamin D analogues are both naturally occurring – calcitriol (1α, 25-dihydro- xyvitamin D3) and synthetic analogues- calcipotriol, 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 (Re- PUVA). • 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
  • 96. Essentials in Dermatology88 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. Fig. 10.9: Treatment pyramid of psoriasis Table 10.1: Biologic agents and their mechanism of action Strategy Biologic agents Reduction of the number Alefacept, denileukin of pathogenic T cells diftitox Inhibition of T-cell Efalizumab, daclizumab, activation and migration siplizumab, CTLA4Ig, galiximab, Modulation of the immune Ilodecakin, oprelvekin system Blockage of the activity of Etanercept, infliximab, inflammatory cytokines adalimumab, ABX-IL8
  • 97. Papulosquamous Disorders 89 • 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 dermato- logic manifestations. 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 • 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 blennor- rhagica) 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,
  • 98. Essentials in Dermatology90 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, 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. 10.13: Lichen planus–violaceous, flat-topped papules Fig. 10.14: Lichen planus–wrist involved, Koebner phenomenon also seen
  • 99. Papulosquamous Disorders 91 • 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. 10.15: Lichen planus–flexor aspect of arm involved Fig. 10.16: Lichen planus–hypertrophic violaceous papules and plaques over legs Fig. 10.17: Lichen planus–trunk involved by typical violaceous papular lesions Fig. 10.18: Lichen planus–an annular lesion over the glans penis Fig. 10.19: Lichen planus–male genitalia involved by lichen planus
  • 100. Essentials in Dermatology92 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), 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 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-
  • 101. Papulosquamous Disorders 93 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 Fig. 10.24: Lichen planus actinicus–typical hypopigmented halo around pigmented violaceous lesions over the face (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 amylo- idosis, warts. • Linear lesions: Lichen striatus, linear epidermal naevus, linear psoriasis. • Annular lesions: Granuloma annulare, secondary syphilis, psoriasis • Lichen planopilaris: For early lesions- keratosis pilaris, other follicular keratoses, Darier’s disease, early pityriasis rubra pilaris. For advanced lesions-discoid lupus erythe- matosus, 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,
  • 102. Essentials in Dermatology94 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 triam- cinolone 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 anti- inflammatory 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 corticos- teroids, tetracycline, betamethasone mouth- washes 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
  • 103. Papulosquamous Disorders 95 2. Lichen scrofulosorum (grouped follicular papules in small patches on trunk), 3. Lichen planus, 4. Sarcoidosis, 5. Disseminated granuloma annulare, 6. Eruptive xanthomas, 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 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 • 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”
  • 104. Essentials in Dermatology96 • 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. 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 Fig. 10.29: Inverse pityriasis rosea – lesions over the face 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) • 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. 10.30: Pityriasis rubra pilaris – follicular papular lesions coalescing to form plaques over the trunk
  • 105. Papulosquamous Disorders 97 • 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. 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) • 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 (Re- PUVA) 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,
  • 106. Essentials in Dermatology98 • 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 erythro- derma, generalized lymphadenopathy and atypical cells in peripheral smear (more than 10%). • It can be a manifestation of internal malignancy. 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. 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.
  • 107. Eczema 99 11 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.
  • 108. Essentials in Dermatology100 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
  • 109. Eczema 101 Fig. 11.1: Atopic dermatitis—face Figs 11.2 and 11.3: Atopic dermatitis–discoid eczematous lesions also appearing on flexor aspect of limbs in a child Fig. 11.2 Fig. 11.3
  • 110. Essentials in Dermatology102 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, azathio- prine, Chinese herbal medicines, interferons, thymopentin, human interferon gamma and plasmapheresis. • Algorithmic approach to management depending upon severity of AD.
  • 111. Eczema 103 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 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 oily- looking, 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. • 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.
  • 112. Essentials in Dermatology104 • ‘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 acroder- matitis 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 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
  • 113. Eczema 105 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 deep- seated 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 pompholyx- like 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 • Pityriasis alba is a common disorder in children that is characterized by an asymptomatic, hypopigmented, slightly elevated, fine, scaling plaque with indistinct borders. Fig. 11.6: Nummular eczema—coin shaped eczematous lesions over the leg
  • 114. Essentials in Dermatology106 • 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. 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
  • 115. Eczema 107 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. • 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) • 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). Fig. 11.7: Lichen simplex chronicus—thickening, and pigmentation of ankle Fig. 11.8: Lichen simplex chronicus— involving nape of neck Fig. 11.9: Lichen simplex chronicus-involving female external genitalia
  • 116. Essentials in Dermatology108 • 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. Fig. 11.10: Prurigo nodularis—raised itchy nodular lesions over the legs and dorsa of feet Fig. 11.11: Lichen striatus—linearly arranged flat topped papular lesions over the chest of a child
  • 117. Eczema 109 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 hypersensi- tivity (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. dermato- phytide 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 aggra- vates, 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
  • 118. Essentials in Dermatology110 adolescence. Patients are advised to use emollients, 100% cotton socks and leather shoes or sandals. 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
  • 119. Eczema 111 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. Fig. 11.14: Contact dermatitis—lichenoid dermatitis over the forehead due to hair dye Fig. 11.15: Contact dermatitis—dermatitis due to rubber chappal Fig. 11.16: Common agents involved in contact dermatitis of the face
  • 120. Essentials in Dermatology112 DIFFERENCES BETWEEN IRRITANT CONTACT AND ALLERGIC CONTACT DERMATITIS Irritant contact dermatitis Allergic contact dermatitis *People at risk Everyone Genetically predisposed *Mechanism of response Nonimmunologic Delayed hypersensitivity *Prior exposure required No Yes *Nature of substance Organic solvents, soap Low molecular weight hapten (metal, formalin) *Concentration of substance required Usually high May be low *Symptoms Severe, stinging or burning sensation Pruritus *Lesions Large tense bullae with necrosis Papules or papulovesicles *Involvement of non-exposed sites No Yes *Type of inflammatory cells Neutrophils Eosinophils and lymphocytes *Patch test Not useful Diagnostic 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. INFECTIVE DERMATITIS (INFECTIOUS ECZEMATOID DERMATITIS, MICROBIAL ECZEMA) • Infective eczema is caused by micro- organisms 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
  • 121. Eczema 113 • Light sensitivity decreases with repeated sun exposure, this phenomenon is referred to as hardening. • Differential diagnosis: Lupus erythe- matosus, 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.
  • 122. Essentials in Dermatology114 12 Vesiculobullous Disorders Vesiculobullous disorders cause significant morbidity and mortality in dermatology. While a numberofdisordersofvariedetiologycanpresent 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 dermo- epidermal 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 auto- immune 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 (Senear- Usher 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 (cica- tricial pemphigoid)
  • 123. Vesiculobullous Disorders 115 c. Pemphigoid gestationis (Herpes gesta- tionis) 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 groupsofdisorderswithspecialfocusonthemore common entities. EPIDERMOLYSIS BULLOSA • Epidermolysis bullosa (EB) comprises a group of genetically determined skin disorders characterized by blistering of the skin (Fig. 12.1)andmucosaeatbirthorsoonafterwards, 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). • 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 mucosaemaybeseverelyinvolved.Teethmay 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. 12.1: Epidermolysis bullosa—baby showing multiple erosions Fig. 12.2: Epidermolysis bullosa dystrophica–knee showing hemorrhagic bullae with scarring, milia and pigmentation
  • 124. Essentials in Dermatology116 – Onset at birth or early infancy – Blisteringofskinmainlyovertraumaprone 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 contra- ctures and deformities. • Gene therapy appears as a realistic goal in the future. PEMPHIGUS • 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 severalotherminortypes.Themajortypesare: – Pemphigus vulgaris (variant – Pemphigus vegetans): level of split-suprabasal. – Pemphigus foliaceus (variant – Pem- phigus erythematosus): level of split – subcorneal. • The other minor types of pemphigus include paraneoplastic pemphigus, drug induced pemphigus, IgA pemphigus and neonatal pemphigus. Pemphigus Vulgaris • Mostcommonformofpemphigus,accounting for up to 80% of pemphigus cases. Occurs at anyage,mostcommonlybetweenfourth-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). Fig. 12.3: Epidermoloysis bullosa dystrophica– albopapuloid lesions over the dorsa of feet and some of the toenails completely lost
  • 125. Vesiculobullous Disorders 117 • Skin – flaccid bullae on normal or erythe- matous 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 thatshownotendencytohealspontaneously. • 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
  • 126. Essentials in Dermatology118 • 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 immuno- fluorescence done to determine levels of pathogenic antibodies in the sera of the 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 cementingsubstanceofupperepidermalcells- subcorneal 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). 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
  • 127. Vesiculobullous Disorders 119 • Oral lesions are uncommon. • Nikolsky’s sign is invariably positive (Fig. 12.13). 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. Fig. 12.10: Pemphigus vegetans—vegetating moist lesions occurring in the axilla Fig. 12.11: Pemphigus vegetans—vegetating moist lesions in the retroauricular area Fig. 12.12: Pemphigus foliaceous—moist scaly lesions in seborrheic areas of the face Fig. 12.13: Nikolsky’s sign – tangential pressure with finger tip producing moist erosion due to peeling of skin
  • 128. Essentials in Dermatology120 Pemphigus Erythematosus It is a variant of pemphigus foliaceous charac- terized 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 trunkaresimilartothoseinpemphigusfoliaceous. 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 polymor- phous blistering eruption with muco- cutaneous 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 differen- tiatedfrompemphigus.Onrareoccasions,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. Whenbothskinandoralmucosaareinvolved, itcloselyresembleserythemamultiforme,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 dexa- methasone cyclophosphamide pulse regimen consisting of 100 mg of IV dexamethasone in 5% dextrose infusion on 3 consecutive days of each month combined with IV cyclopho- sphamide 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.
  • 129. Vesiculobullous Disorders 121 BULLOUS PEMPHIGOID (BP) • Autoimmune subepidermal blistering disorderoftheelderly,withonsetusuallyafter 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 dermis- subepidermal 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. • 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 immunofluo- rescence 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. Fig. 12.14: Bullous pemphigoid—itchy urticarial lesions over the thigh developing into tense bullae Fig. 12.15: Bullous pemphigoid—involving lower back
  • 130. Essentials in Dermatology122 Differential Diagnosis Bullous pemphigoid can be easily differentiated frommostotherblisteringdisorderssuchaslinear IgA disease, chronic bullous disease of childhood, dermatitis herpetiformis, erythema multiforme and pemphigus by histology and immuno- fluorescence. 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 self- limiting course. It may be fatal in the active stage in the elderly or debilitated patients. 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, mycopheno- late mofetil, intravenous immunoglobulin therapy and plasmapheresis. 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 oropha- ryngeal 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. • Herpesgestationisisanon-viralautoimmune 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, premen- strually or with oral contraceptive pills (OCPs). Direct immunofluorescence shows linearC3depositsattheBMZwithIgGinsome cases. Fig. 12.16: Cicatricial pemphigoid— tense bulla over the tongue Fig. 12.17: Cicatricial pemphigoid—face showing symblepharon
  • 131. Vesiculobullous Disorders 123 Characteristic Bullous pemphigoid Pemphigus vulgaris Age > 60 years Middle age Pruritus ++ Not present Blister Tense Flaccid Sites Flexures, groins, axillae, abdomen Face, scalp, trunk, pressure points Erosion Spontaneously heal Extend peripherally Nikolsky’s sign Negative Positive Oral lesions 40 % less severe, almost never a 80–90 % severe commonly the presenting feature presenting symptom Prognosis Benign, self limiting Poor without treatment 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. • Pruritusisthefirstandpredominantsymptom 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. • Histologicalexamination bestdoneonlesions thathavenotblisteredorrupturedandreveals 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
  • 132. Essentials in Dermatology124 • Direct immunofluorescence is the most reliable diagnostic criterion and should be performed on clinically normal skin (preferablyofthebuttocks).Itrevealsgranular IgA deposits in dermal papillae. • Indirect immunofluorescence is negative for anti-BMZ or dermal autoantibodies but antithyroid and antigliadin antibodies may be seen. 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. 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 charac- terized by linear deposition of IgA at basement membrane zone. It consists of two main entities- 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. 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). Fig. 12.20: Chronic bullousdermatosis of childhood— clustering of tense bullae around the mouth
  • 133. Vesiculobullous Disorders 125 • 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 combined with low dose steroids in refractory cases. Disorder Site of split Pathogenic antibody P. vulgaris Suprabasal IgG P. foliaceous/ Subcorneal IgG erythematosus Paraneoplastic Suprabasal IgG pemphigus BP / HG / CP Subepidermal IgG and C3 EBA Subepidermal IgG Dermatitis Subepidermal IgA herpetiformis CBDC Subepidermal IgA (Note: Epidermolysis bullosa are a group of genetic disorders with structural defects but NO autoantibodies.) EPIDERMOLYSIS BULLOSAACQUISITA (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 collagenVIIcausesit.CollagenVIIisthemajor 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. Fig. 12.21: Chronic bullous dermatosis of childhood– lower limbs showing “cluster of jewels” appearance at many sites
  • 134. Essentials in Dermatology126 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 presen- tation– 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, metho- trexate, 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.
  • 135. Cutaneous Tuberculosis and Atypical Mycobacterial Infections 127 13 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 Inoculation +++ - - *Miliary TB Hematogenous ++ - - Secondary TB *Lupus vulgaris Inoculation +/- +++ +++ *TBVC Inoculation + +++ +++ *Scrofuloderma Contiguous ++ +++ ++ *TB gumma Hematogenous ++ + + *Orificial TB Autoinoculation ++ + - Tuberculids *Papulonecrotic Hematogenous - +++ +++ *Lichen scrofulosorum “ - +++ +++ *Erythema induratum “ - +++ +++ 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.
  • 136. Essentials in Dermatology128 TUBERCULOUS CHANCRE 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. 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. LUPUS VULGARIS 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. 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. 13.1: Lupus vulgaris—plaque lesion with active infiltrated border with central scarring over the thigh Fig. 13.2: Lupus vulgaris—verrucous plaque with trailing scar and depigmentation in the groin
  • 137. Cutaneous Tuberculosis and Atypical Mycobacterial Infections 129 • 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 hyper- pigmented 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 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 toaverrucousplaquewithserpiginousborder. Differential Diagnosis • TBVC should be differentiated from other warty lesions such as verruca vulgaris, lupus vulgaris (usually not hyperkeratotic, diascopy demonstrates apple jelly nodules), chromo- blastomycosis, 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 involvementofskinoverlyingatuberculousfocus such as lymph node, bone, joint, epididymis or lacrimal gland. • It manifests as bluish red nodules overlying lymphnodesorjointsthatbreakdowntoform undermined ulcers with a bluish edge (Figs 13.5 and 13.6). Fig. 13.3: Tuberculosis verrucosa cutis—verrucous plaque with fissuring and foetid discharge over the sole Fig. 13.4: Tuberculosis verrucosa cutis—verrucous plaque with fissuring over the dorsum of great toe
  • 138. Essentials in Dermatology130 • 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 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) It occurs due to hematogenous dissemination during periods of bacillemia and lowered resistance • Common in poorly nourished children • Presents as firm subcutaneous nodules that softenandulceratetoformunderminedulcers. 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 Fig. 13.5: Scrofuloderma—subcutaneous nodules and ulcerated lesions along with scarring in the neck Fig. 13.6: Scrofuloderma—ruptured bluish nodules with undermined edges in the axilla Fig. 13.7: Scrofuloderma—sinuses and fistulae healing with puckered scarring over the back
  • 139. Cutaneous Tuberculosis and Atypical Mycobacterial Infections 131 • 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, Churg- Strauss granuloma, lymphomatoid papulosis, perforating granuloma annulare, perforating collagenosis and necrotizing or septic vasculitis share clinical and histologic features with papulonecrotic tuberculid. 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. • 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. Fig. 13.8: Orificial tuberculosis—painful, shallow ulcers with undermined edges around the anus
  • 140. Essentials in Dermatology132 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 pyrazi- namide. 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.
  • 141. Cutaneous Tuberculosis and Atypical Mycobacterial Infections 133 SUMMARY OF ATYPICAL MYCOBACTERIAL INFECTIONS Organism Disease Clinical Features Treatment M.marinum Swimming pool granuloma, Warty plaque or sporotrichoid Rifampin and ethambutol or fish tank granuloma lesions on knees, elbows and tetracycline feet M.ulcerans Buruli ulcer Subcutaneous nodules rupture Surgery is the treatment of choice to form shallow ulcers with followed by rifampin or necrotic fat in the floor cotrimoxazole M.avium complex Nodules, leg ulcers and papules Combined therapy of isoniazid, Disseminated heterogenous rifampin and streptomycin. infection in HIV patients M.chelonae Injection Cellulitis and subcutaneous Surgical debridement and amikacin M.fortuitum abscess nodules or doxycycline or ciprofloxacin M. scrofulaceum Cutaneous abscesses Cutaneous abscesses, chronic Treatment- surgical treatment ulcerative and nodular skin of infected lymph node. lesions, and cervical Widespread disease- treatment lymphadenitis same as in M avium complex
  • 142. Essentials in Dermatology134 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, well- defined 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 lookslikeacarpetpenetratedbyseveralcarpet 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).
  • 143. Connective Tissue Disorders 135 • The risk is higher in patients with disseminated DLE (22%). 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 non- sun exposed skin always negative. Negative • Other types are hypertrophic, tumid, lupus erythematosus profundus, mucosal DLE, chilblain lupus, etc. Prognosis • DLE has a chronic progressive course. Patients with hematological and serological abnormalities have 6.5% risk of developing overt SLE. Fig. 14.1: Discoid lupus erythematosus—well defined, discoid, erythematous plaques over the chest Fig. 14.2: Discoid lupus erythematosus—discoid lesions involving the face Fig. 14.3: Discoid lupus erythematosus—discoid lesions evolving with central depigmentation and atrophy Fig. 14.4: Discoid lupus erythematosus—scarring alopecia
  • 144. Essentials in Dermatology136 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 browninitially,laterbecomingredbrownincolor, have a characteristic translucence and wood- grains appearance, telangiectasia may be seen on the surface of the lesions, no prominent follicles), tineafaciei(KOHexamination),granulomafaciale (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. 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 acid- Schiff(PAS)positivebasementmembraneand 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 (Hydroxychloro- quine 200-400 mg daily or chloroquine 250 mg daily, monitoring by an ophthalmo- logist required every 6-12 months), dapsone (50-100 mg daily), thalidomide (50-200 mg daily), corticosteroids (prednisolone 40 mg Fig. 14.5: Generalized discoid lupus erythematosus—discoid lesions involving the trunk Fig. 14.6: Generalized discoid lupus erythematosus—discoid lesions involving the feet
  • 145. Connective Tissue Disorders 137 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. 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 isusuallybetween16and42yearsoccurringmore 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. • 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. Fig. 14.7: Systemic lupus erythematosus—malar and photosensitive rash over the face
  • 146. Essentials in Dermatology138 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—documentedbyECGorrub 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 drugsorknownmetabolicderangements, e.g. uremia, ketoacidosis, or electrolyte imbalance or b. Psychosis—in the absence of offending drugsorknownmetabolicderangements, 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/mLontwoormore occasions or d. Thrombocytopenia—<100,000/mL in the absence of offending drugs. 10. Immunologic disorder: a. Anti-DNA—antibody to native DNA in abnormal titer or b. Anti-Sm—presence of antibody to Sm nuclear antigen or c. Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test. 11. Antinuclear antibody (ANA): An abnormal titer of antinuclear antibody by immuno- fluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with “drug-induced lupus” syndrome. Note: The proposed classification is based on 11 criteria. For the purpose of identifying patients in clinical studies, a person shall be said to have SLE if any 4 or more of the 11 criteria are present, serially or simultaneously, during any interval of observation. Chief Cutaneous Features • Butterfly rash. • Photosensitivity. • Raynaud’s phenomenon. • Non-scarring alopecia-short hairs in the frontal region are referred to as lupus hairs. • Urticarial vasculitis. • Mouth ulceration. • Bullous lesions. • Chronic discoid LE lesion. • Cutaneous vasculitis. • Other features are vasculopathy, periungual telangiectasia, leg ulcers, erythema multi- forme,thrombophlebitis,peripheralgangrene, etc. Investigations • Complete blood count, ESR. • Urine analysis for microscopic hematuria and proteinuria.
  • 147. Connective Tissue Disorders 139 • Skin biopsy- There is no single diagnostic pathological feature in the skin, but a combination of features aids diagnosis. Some changes are similar to DLE. The primary pathological lesions of SLE are fibrinoid necrosis, collagen sclerosis, necrosis and basophilic body formation and vascular endothelial thickening. • LEcelltesttodemonstrateLEcell(aneutrophil containing engulfed nuclear material) or rosette phenomenon (neutrophils surroun- ding nuclear debris, trying to engulf it). • Lupus band test- deposits of IgG and C3 along the basement membrane on normal, non-sun exposed skin suggest SLE but is no longer an accepted criterion. It positively correlates with the presence of anti-ds DNA antibodies and with risk for developing LE nephritis. • C3, C4, CH50 levels. • Serum globulins are frequently raised especially gamma globulin. • Rheumatoidfactoroccursinapproximate40% cases. • ANA (Commonest pattern is homogeneous; peripheral pattern-predictor of renal involvement). • ndsDNA. • Antibodies-SSA (Ro), SSB (La), Sm, nRNP. Differential Diagnosis SLEmustbedifferentiatedfromdermatomyositis, erythema multiforme, polyarteritis nodosa, acute rheumatic fever, rheumatoid arthritis, pellagra, pemphigus erythematosus, drug eruption, hyperglobulinemic purpura, Sjogren’s syndrome, necrotizing angiitis and myasthenia gravis. In SLE, there may be fever, arthralgia, weakness, lassitude, diagnostic skin lesions, an increased ESR, cytopenias, proteinuria, immunoglobulin deposition at dermoepidermal junction and a positive ANA test. Biopsies of skin lesions and involved kidney may also be diagnostic. Treatment SLE with only cutaneous lesions and arthritis: • Photoprotection. • NSAID’s, antimalarials, prednisolone ( 1-2 mg per kg body weight daily). • Dapsone most effective in urticarial vasculitis and bullous SLE. Severe Disease with End-organ Damage • Steroid pulse therapy. • Immunosuppressants such as azathioprine (100-150 mg daily), cyclophosphamide (50- 100 mg daily), methotrexate (7.5-20 mg weekly),chlorambucil,mycophenolatemofetil (2 gm daily) and cyclosporine (5 mg/kg body weight daily). Experimental Therapies • Intravenous immunoglobulins, plasma- pheresis, anti CD20 (rituximab), -CD40 and – TNF alpha antibodies. Course and Prognosis The course of the SLE is very variable. Acute fulminating cases are much less common than subacute cases, which smoulder on for many years. SCLERODERMA Scleroderma(Gr.Skleros–hard,andderma–skin) is a connective tissue disorder characterized by generalized or localized sclerosis of the skin. The localized type is called morphea. Classification Morphea – Localized (Circumscribed plaque, morphea profundus, bullous, linear, en coup de sabre) and generalized.
  • 148. Essentials in Dermatology140 Systemic sclerosis – LM (Limited cutaneous) SSc, DC (Diffuse cutaneous) SSc. Occupational scleroderma – Polyvinylchloride, perchlorethylene, trichloroethylene, organic solvents, malathion, DDT, epoxy resins, silicosis. Iatrogenic scleroderma – Bleomycin, carbidopa, pentazocine, cocaine, appetite suppressants, silicone or paraffin implants, GVHD. Pseudoscleroderma – Scleroedema of Buschke, Scleromyxoedema, prophyria cutanea tarda, phenylketonuria. Primary systemic amyloidosis, carcinoid syndrome, hypothyroidism. Miscellaneous – Toxic oil syndrome, eosinophilic fascitis. MORPHEA Localized Morphea • Most common form of morphea. • Occurs most commonly in females than males and primarily in young adults. • Seen commonly on the trunk. • The lesion of morphea may begin as erythematous macule, evolve into ivory- colored center and violaceous bordered plaque. • Lesions slowly involute over 3 to 5 years period leaving permanent atrophic skin or normal appearing skin behind. Generalized Morphea • Lesions are more numerous and larger • Often coalesce to involve extensive portions of the body. • Muscle atrophy may be associated. Pansclerotic Morphea (Morphea Profunda) • Sclerosis involves dermis, panniculus, fascia, muscle and bones. • There is disabling limitation of the joints. En Coup De Sabre • It is a variant of linear scleroderma involving scalp parasagitally on frontal scalp and forehead (Figs 14.8 and 14.9). • Often has the configuration of the stroke of a saber (en coup de sabre). Differential Diagnosis 1. Morphea-like lesions can occur in sarcoidosis and morpheic basal cell carcinoma. Figs 14.8 and 14.9: En coup de sabre—linear indurated depressed lesion in the midline over the forehead Fig. 14.8 Fig. 14.9
  • 149. Connective Tissue Disorders 141 Histopathology is required to differentiate between them. 2. Lichen sclerosus atrophicus (ivory white plaques with follicular delling and atrophy) and subcutaneous zygomycosis may resemble morphea. Fingers can be insinuated below the plaques of subcutaneous zygomycosis. 3. Pseudoscleroderma especially porphyria cutanea tarda and graft versus host disease. 4. Drug reaction (bleomycin induced sclerosis, atrophic morphoeic plaques from intra- muscular injection of vitamin K or subcutaneous corticosteroid injections). Treatment • Natural history is towards spontaneous resolution. • Topical steroid, intralesional steroids and oral chloroquine. • Topical calcipotriol. • Bath PUVA or UVA1. • For widespread or rapidly advancing disease considertherapyusuallyreservedforsystemic sclerosis (corticosteroids, d-penicillamine, cyclopsporine, low dose methotrexate, etretinate, phenytoin, plasmapheresis). • Physiotherapy may be helpful in preventing joint deformities. SYSTEMIC SCLEROSIS It is characterized by cutaneous and internal organ fibrosis. Raynaud’s phenomenon is the earliest feature and may precede the onset of disease by months or years. The heart, lungs, gastrointestinal, kidney and other organs may be involved. Pathogenesis Exact cause of systemic sclerosis is unknown. Important steps in its pathogenesis include: • Excessive synthesis of collagen and matrix macromolecules. • Endothelial cell injury. • Dysregulation of the immune system. Classification • Diffuse disease: Characterized by extensive proximal and truncal skin induration. • Limited disease: Induration is confined to hands, forearm, face, and legs. Its variant is called CREST syndrome (Thibierge- Weissenbach syndrome) (Calcinosis, Raynaud’s phenomenon, Esophageal dys- function, Sclerodactyly and Telangiectasia). American Rheumatism Association Criteria Major • Scleroderma proximal to the digits, affecting limbs, face, neck and trunk. Minor • Sclerodactyly (Fig. 14.10). • Digital pitted scarring (Fig. 14.11). • Bilateral basal pulmonary fibrosis. One major criterion or two or more minor criteriasuggestthediagnosisofsystemicsclerosis. Note: These criteria have 97% sensitivity and 98% specificity. Fig. 14.10: Progressive systemic sclerosis— sclerodactyly with calcification over the inter- phalangeal joints of fingers
  • 150. Essentials in Dermatology142 Cutaneous Manifestations Three phases of dermal involvement can be distinguished: 1. Edematous phase (stiff, puffy, fingers) 2. Indurative phase (hard, tight, hide bound) 3. Atrophic phase (softened skin, burnt out). Hands and Feet • Early: Raynaud’s phenomenon. • Swollen or tumid fingers and hands. • “Round finger pad sign”-fingers lose their normal peaked contour but rather appear as rounded hemisphere when viewed from the side. • Painfululcerationsatfingertips(Ratbiteulcer) with pitted scars. • Late: sclerodactyly (induration of skin over the fingers) with tapering of fingers (Figs 14.10 and 14.11). • Skin is tightly bound down. • Leathery crepitations over joints and flexion contractures. • “Heuck-Gottron sign”- loss of cuticle with telangiectases. • Bony resorption. • Atrophy of the pulp of the fingers. • Gangrene of the fingers. • Pigmentation. • Calcinosis. Face • Periorbital edema is the early manifestation • Late manifestations include: Mask like facies (difficulty in eversion of lower eyelids), thinning of lips, microstomia, radial perioral furrowing, small sharp nose (Fig. 14.12), telangiectasia (mat-like) and diffuse hyperpigmentation. • Forehead is smooth and shiny, and skin is bound down and hard. • There is reduced wrinkling on the forehead and mandibular atrophy. Trunk • Early: tense, stiff and waxy appearing skin that cannot be pinched and folded. • Late: impairment of respiratory movement of chest wall and of joint mobility. • “Neck sign”-ridging and tightening of the neck on extension due to sclerosis. Fig. 14.11: Progressive systemic sclerosis—finger tip pits due to scarring Fig. 14.12: Progressive systemic sclerosis—mask like facies, thinning of lips and small sharp nose
  • 151. Connective Tissue Disorders 143 Other Changes “Salt and pepper” pigmentation (Fig. 14.13), gangrene of fingers, mat like telangiectasia, leg ulcers and livedo reticularis. Organ Involvement in PSS • Esophageal fibrosis, pulmonary interstitial fibrosis, myocardial fibrosis, small intestinal fibrosis, large intestinal fibrosis, renal involvement, skeletal muscle atrophy and thyroid fibrosis. • Others are bone, eye, CNS, teeth, tendons. Investigations • Routine tests such as complete hemogram, liver function tests, sedimentation rate, C-reactive protein. • Skin biopsy- Dermal sclerosis typically results in rectangular punch biopsy specimen. As the dermis replaces the subcutaneous tissue, eccrine glands appear to be in the mid portion of the thickened dermis. The subcutaneous fat is quantitatively reduced and adventitial fat is lost. On DIF testing of skin the nucleolus may be stained in the keratinocytes if antinucleolar circulating antibodies are present and a “pepper dot” epidermal nuclear pattern may be seen in CREST patients who haveanticentromereantibodiesintheirserum. • Nail fold capillary microscopy. • ANA (+ve in more than 90%), Ab-SSA, SSB, Sm, nRNP,Scl-70(specificfordiffusesystemic sclerosis), anticentromere antibody (specific for CREST syndrome). • Rheumatoid factor positive in 30% • Organ workup: urine analysis, barium swallow, esophageal manometry, barium enema, chest x-ray and pulmonary function test. Differential Diagnosis 1. Generalized morphea (Raynaud’s phenomenon is rare, systemic involvement is unusual, no atrophic stage, no facial telangiectasia or perioral furrowing, skin of trunk and limbs are equally involved) 2. Pseudosclerodermas (Specific features of each should be looked for) 3. Occupational and iatrogenic scleroderma (History of specific exposure should arouse the suspicion). 4. Other collagen vascular disorders- mixed collagen vascular disorders, overlap syndromes 5. Graft versus host disease Prognosis and Cause of Death • Course of the disease is variable. Death occurs fromintercurrentinfection,respiratoryfailure, cardiac failure, renal failure, sometimes, malignanthypertensionandperforationofthe gastrointestinal tract. Other Conditions Where Sclerodermoid Changes are Seen Phenylketonuria, progeria, Rothmund-Thomson syndrome, Werner’s syndrome, porphyria cutanea tarda, primary systemic amyloidosis, Hashimoto’s disease, carcinoid syndrome, Fig. 14.13: Progressive systemic sclerosis—“salt and pepper pigmentation”—depigmentation with speckled hyperpigmented macules over the front of the chest
  • 152. Essentials in Dermatology144 childhood diabetes mellitus and drugs (bleomycin, pentazocine, carbidopa, and 5-hydroxytryptophan). Treatment There is no specific treatment and no therapy is known to alter the course of a disease. Treatment is primarily directed towards complications. Pharmacological agents used for systemic sclerosis can be grouped into various categories. • Collagen modulators: D-penicillamine (125 mg alternate days, 750-1500 mg per day), relaxins, and interferons. • Vasoactive agents: Captopril, nifedipine and pentoxifylline. • Immunosuppressive agents: Systemic corti- costeroids (prednisolone 0.5 mg mg per kg body weight daily), azathioprine (1-2 mg mg per kg body weight daily), cyclophosphamide (2 mg per kg body weight daily), cyclosporine (3-5 mg per kg body weight daily) and methotrexate (20-30 mg weekly). Forinternalorganinvolvement—Angiotensin converting enzyme inhibitors are treatment of choice for renal hypertension, proton pump inhibitors (omeprazole 20-40 mg daily) indicated for esophageal dysfunction and for pulmonary hypertension intravenous prostacyclin; inter- stitial lung disease may respond best to cyclophosphamide. Physical therapy can help avoid contractures and retain function. DERMATOMYOSITIS It is a systemic, inflammatory disease involving primarily skin and muscles. Symmetric, proximal muscle weakness occurs especially in the hips, thigh, and upper arm. Patients with only muscular symptoms and signs but no cutaneous findings are said to have polymyositis. These can be associated with malignancies especially in adulthood – carcinoma of lung, breast, female genital tract, stomach, kidney and testes. Cutaneous Manifestations of Dermatomyositis Pathognomonic • Gottron’s papules: Violaceous, flat topped papules on interphalangeal joints and knuckles. Similar lesions may occur over other bony prominences such as knees, elbows and medial malleoli. • Gottron’ssign:Symmetricmacularviolaceous erythema with or without edema over the above mentioned sites. Characteristic • Periorbital violaceous erythema with associated edema of eyelids and periorbital tissue (heliotrope rash) (Fig. 14.14). • Periungual telangiectasia with associated dystrophic cuticles. • Macular violaceous erythema overlying the dorsal hands, extensor forearms and arms, deltoids, posterior shoulders, nape of neck, V area of neck, upper chest and forehead. “Shawl sign”-erythema and scale (with or without poikiloderma) over the shoulder regions. • Mechanic’s hands: Bilaterally symmetrical confluenthyperkeratosisdistributedalongthe Fig. 14.14: Dermatomyositis—“Heliotrope rash”— periorbital violaceous erythema with associated edema of eyelids
  • 153. Connective Tissue Disorders 145 ulnar aspects of the thumbs and radial aspects of the index and middle fingers with occasional extension to the palmar surface. Compatible • Poikiloderma atrophicans vasculare • Calcinosis cutis. Systemic features include arthritis (25%), oral ulcers (20%), calcinosis (distinctive feature of juvenile dermatomyositis), pulmonary fibrosis (20%), gastrointestinal ulcerations and hemorrhages, occasionally myocarditis or myopathy. Investigations • Skin biopsy, muscle biopsy, muscle enzymes, electromyography, ANA, Ab-SSA, SSB, Sm, nRNP, Jo-1and PM-1. Diagnostic Criteria 1. Progressive symmetric proximal muscle weakness. 2. Elevated muscle enzyme levels. 3. Abnormal electromyogram. 4. Abnormal muscle biopsy. 5. Characteristic cutaneous manifestations. Definite: 5 plus three other criteria. Probable: 5 plus two other criteria. Differential Diagnosis Includes other myopathies (inclusion body myositis, muscular dystrophy, neuromuscular atrophy,myastheniagravis,thyrotoxicmyopathy, Cushing’s disease, sarcoidosis, alcoholism), drugs (lipid lowering agents, hydroxyurea, NSAIDs), overlap syndromes, vasculitis, polymyalgia rheumatica and trichinosis. Treatment • Skin disease: Topical steroids, hydroxy- chloroquine. • Muscle disease: Systemic corticosteroids are first line therapy. Second line agents are methotrexate (5-15 mg weekly) and azathioprine (1-3 mg per kg body weight daily). • Intravenous immunoglobulins are indicated for resistant cases, children with vasculitic component and those with steroid induced diabetes mellitus. • Bed rest during flares, physical therapy when stable. • Appropriate treatment of underlying malignancy where it is associated. OVERLAP SYNDROME • The term overlap syndrome may be used when patients exhibit symptoms of more than one connective tissue disease. • Such patients may meet diagnostic criteria for one disease but also have atypical manifestations or findings suggestive of second diagnosis. • Systemic sclerosis combined with dermato- myositis is the most frequently seen overlap syndrome. MIXED CONNECTIVE TISSUE DISEASE • This entity was first described by Sharp and colleagues in 1972. • These patients, predominantly female, show features of SLE, systemic sclerosis, dermato- myositis and polymyositis. • All patients have high titer of antibody to U1 RNP (ribonucleoprotein). • Prominent clinical features include myositis, pulmonary hypertension, Raynaud’s pheno- menon, oesophageal hypomotility, swollen hands and sclerodactyly. SJÖGREN’S SYNDROME (SS) • Sjögren in 1933 described a triad of keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis.
  • 154. Essentials in Dermatology146 • Dry eyes and dry mouth occur in primary Sjögren’s syndrome or if associated with other connective tissue disease then referred to as secondary Sjögren’s syndrome. • Most patients are aged 50 years or older and are women. • Clinical features include xerostomia, rhinitis sicca, vaginal dryness and dry eyes (Fig. 14.15). • Skin manifestations of SS include vasculitis, xerosis and annular erythema. • Rheumatoid factor is usually positive. • 80% of patients have anti Ro/SSA antibodies. • Increased risk of developing lymphoreticular malignancies. • No specific treatments available, only symptomatic management. LICHEN SCLEROSUS ET ATROPHICUS (LSA) • It is a chronic disease of the skin and mucous membrane of unknown origin predominantly affecting the females. • Early lesions of LSA are ivory white, polygonal, flat-topped papules or plaques withfollicularplugs(delling).Thelesionsmay coalesce into large atrophic plaques. • In women, involvement of the vulvar and perianal areas leads to the typical “figure of Fig. 14.15: Sjögren’s syndrome—face showing submandibular salivary gland enlargement eight” or “ hour glass” appearance (Fig. 14.16) • LSA of the penis in adults (Balanitis xerotica obliterans) presents with acquired phimosis or recurrent balanitis (Fig. 14.17). • LSA of vulva (Kraurosis vulvae) usually seen in postmenopausal women. • LSA of the genitalia have increased risk for squamous cell carcinoma (Fig. 14.18). Fig. 14.16: Lichen sclerosus et atrophicus of the vulva- typical “figure of eight” or “hour glass” appearance Fig. 14.17: Lichen sclerosus et atrophicus—ivory white induratedringlikelesioninvolvin preputial orifice
  • 155. Connective Tissue Disorders 147 Differential Diagnosis On trunk- morphea, annular atrophic plaque type of DLE and vitiligo, female genitalia-vitiligo, chronic dermatitis, erosive lichen planus, autoimmune bullous diseases, male genitalia- balanitis in all its variants, idiopathic phimosis, erosive lichen planus. Fig. 14.18: Lichen sclerosus et atrophicus—male penis with squamous cell carcinoma Treatment Medical—Topical steroids or intralesional steroids, topical pimecrolimus or tacrolimus, topical testosterone, topical tretinoin, UVB and bath PUVA therapy. Surgical correction of adhesions may be required.
  • 156. Essentials in Dermatology148 Human race has a wide variation in normal skin color (pale white, light brown, dark brown and black). Various skin chromophores like brown (melanin), red (oxyhemoglobin), blue (deoxy- hemoglobin) and yellow-orange (carotene) are responsible for skin color. Of course, melanin is the major component of skin color. Skin color depends on the genetic make-up of an individual and environmental effects like ultraviolet radiation exposure. Melanocyte is the sole site of melanin synthesis. Pigmentary disturbances include decrease or absence or increase in pigmentation which could be either epidermal or dermal. These pigmentary changes are a result of changes in number of melanocytes or amount of melanin. Pigmentary disorders may be congenital or acquired, circumscribed or generalized, hypomelanotic (Vitiligo, albinism, piebaldism, Waardenburg’s syndrome) or hypermelanotic (Melasma, freckles, lentigo, Peutz Jeghers syndrome).Inthischapter,onlythecommonones are discussed. VITILIGO Vitiligo is defined as a common, dermatological disorder characterized by well-circumscribed, milky-white cutaneous macules devoid of 15 Pigmentary Disorders identifiable melanocytes. In India, the incidence of vitiligo is estimated to be between 3 and 4 %. The term vitiligo is probably derived from the Latin word “vitium”(“blemish”). Many ancient terms are applied to this condition— shwetakustha in the sacred Indian book, Atharva Veda (1400BC), and switra in Manusmriti (200 BC). In South India where the old Dravidian language of Tamil is spoken, the condition is known as ven kushtam—”white leprosy.” Pathogenesis The white macules of vitiligo are the result of a loss of melanocytes. The mechanism(s) by which the melanocytes are lost may be multiple but have not been identified unequivocally. Seven hypo- theses, not mutually exclusive, have been proposed to explain the causation of vitiligo: • Autoimmune: Strengthened by the demonstration of specific autoantibodies to melanocyte cell surface antigens and the association of vitiligo with a variety of autoimmune disorders. • Autocytotoxic: Also called the self-destruction theory, it proposes melanocyte destruction by intracellular retention of various precursors of melanin synthesis. • Neural: Especially proposed to explain the segmental type of vitiligo.
  • 157. Pigmentary Disorders 149 • Biochemical: Accumulation of pteridines (6- biopterin and 7-biopterin) in the vitiliginous skin causes the depigmentation. • Antioxidant deficiency theory: There is an increased level of norepinephrine and catecholamine derivatives in vitiligo skin which leads to tissue ischemia and increased activityofmonoamineoxidaseenzyme,which in turn causes excess production of stress related hydrogen peroxide. Reduced catalase activity in vitiligo skin leads to impaired degradation of H2O2 and accumulation of superoxide radicals causing depigmentation. • Melanocyte growth factor reduction hypothesis: Invitiligo,thereisreducedmelanocytegrowth factors derived from keratinocytes, fibroblasts and other tissues. • Intrinsic (genetic) theory: An underlying genetic/intrinsic factor predisposes some individuals to be more prone to develop vitiligo. Clinical Features • The diagnostic lesion of vitiligo is the typical vitiligo macule, which is of variable size, round/oval in shape, has a milky white color and scalloped margins (Fig. 15.1). • May appear at any age, however, the peak age at onset has been reported to be five to thirty years. • Prevalence is the same in both sexes. • The natural course of the disease is of gradual progression, the lesions increasing both in number and size. In some cases there may be a rapid downhill course of vitiligo and this has been termed ‘galloping vitiligo’ or ‘vitiligo fulminans’. • Segmental vitiligo and vitiligo in children have a better prognosis. • Mucous membrane involvement is also noted in vitiligo and is commoner, or rather, easily detectable in dark-skinned races. • Leukotrichia refers to depigmentation of the hair and may occur in some patients. Classification of Vitiligo Localized • Focal vitiligo: This consists of one or more macules in one area but not clearly in a segmental or zosteriform distribution . • Segmental vitiligo: Number of macules involving a unilateral segment of the body. The lesions stop abruptly at the midline of the affected segment (Fig. 15.1). • Mucosal vitiligo: Vitiligo affecting mucous membranes of the lips, oral cavity or the genitalia (Fig. 15.2). Fig. 15.1: Zosteriform vitiligo—milky white macules in a zosteriform distribution over the back. Fig. 15.2: Vulval vitiligo—female genitalia involved by milky white lesions
  • 158. Essentials in Dermatology150 Generalized • Acrofacial vitiligo: Lesions on the acral areas (hands and feet) (Fig. 15.3) and on the face, very often the perioral areas. • Vitiligo vulgaris: Multiple macules of variable sizesoverwidelyscatteredareasoftentending to bilateral symmetry (Fig. 15.4). • Lip-tip vitiligo: Lesions affecting the tips of the digits and the lips (Fig. 15.5) • Mixed: Any combination- of vitiligo vulgaris and acrofacial vitiligo or of vitiligo vulgaris with segmental vitiligo. • Universal Vitiligo: This is the term used to describe complete or near complete depig- mentation. Special Signs in Vitiligo • Trichrome vitiligo: The trichrome sign, also termed ‘vitiligo gradata’ describes a tan coloredzone(intermediatecolour)betweenthe normal skin and the depigmented macules (Fig. 15.2). ‘Quadrichrome vitiligo’ implies the presence of a fourth color – dark brown – at the sites of perifollicular repigmentation. • Pentachrome vitiligo: Has five colors—white, tan,brownhyperpigmented,blue-greyhyper- pigmented, and normal skin color. • Inflammatory vitiligo: Here skin lesions of vitiligohaveerythematousraisedmargin.This should be differentiated from the erythema of vitiligomaculefollowingexposuretosunlight. • Koebner’s sign: This phenomenon, a common feature of vitiligo, is defined as the development of lesions along the lines of specific trauma such as a cut, burn or abrasion. It may be a marker of disease activity. Fig. 15.3: Acral vitiligo—vitiligo involving hands and feet Fig. 15.4: Vitiligo vulgaris—multiple depigmented and hypopigmented macules over the chest and abdomen (Trichrome vitiligo) Fig. 15.5: Lip tip vitiligo-lesions affecting the tips of the digits and the lips
  • 159. Pigmentary Disorders 151 Association of Vitiligo with Other Diseases Vitiligo has been shown to be associated with autoimmune thyroid disease, Addison’s disease, pernicious anemia, diabetes mellitus and various dermatological disorders like alopecia areata, scleroderma, psoriasis and collagen vascular disorders. The Vogt Koyanagi Harada syndrome is an apparently rare, multisystem disease characterized by vitiligo, poliosis, uveitis, dysacousia, and alopecia. Differential Diagnosis of Localized Vitiligo Includes Naevus depigmentosus (localized hypo- melanosis present since birth), naevus anemicus (pale area due to vasoconsconstriction), leprosy (suspect in an endemic area, shows hypo- anesthetic or anesthetic hypopigmented patch/ es), pityriasis alba (hypopigmented macular lesions have ill defined margins with fine scaling, self limiting course), postinflammatory hypo- melanosis (such cases have preceding history of dermatoses, and the skin lesions are ill defined), tinea versicolor (typical localization to upper trunk, pigmented macular lesions have fine powdery scales, KOH +vity conclusive), ash-leaf macules and confetti depigmentation of tuberous sclerosis, and idiopathic guttate hypomelanosis (tiny porcelain white macules, 2-6 mm with distinct margins, localized to limbs in older individuals). Differential Diagnosis of Generalized Vitiligo Includes Chemicalleukoderma(thereishistoryofexposure tophenolicgermicides;confettimacules;localized to the site of contact), leprosy (suspect in an endemic area, has anesthetic hypopigmented patch/es), mycosis fungoides (unpatterned lesions, diagnosis confirmed by biopsy), postinflammatory hypomelanosis (hypopig- mented macules with ill defined border, history of preceding dermatoses like psoriasis, eczema, pityriasis rosea, etc. in same areas with pattern mimicking it), tinea versicolor (has fine powdery scales over the lesions, in doubt do KOH examination of skin scrapings), Waardenburg’s syndrome, albinism and piebaldism (see next page for last three). Treatment Treatment of vitiligo can be broadly divided into medical and surgical modalities. Medical management Topical therapy 1. Photoprotection: It prevents sunburn and Koebner phenomenon, prevents tanning of uninvolved skin and therefore lessens contrast between normal and depigmented skin. 2. Topical potent corticosteroids. 3. Intralesional corticosteroids: (Triamcinolone acetonide) especially for leukotrichia on scalp. 4. Human placental extract. 5. Topical immunomodulators: Such as tacrolimus (0.1%, 0.03%), pimecrolimus or tacrolimus (0.1%) combined with narrow band UVB three times a week. 6. Calcipotriol: Can be used as monotherapy or combined therapy (sunlight, PUVA, or narrow band UVB, clobetasol). 7. Topical pseudocatalase + calcium + UVB 8. Vitix® : Formulation containing superoxide dismutase and catalase. It removes hydrogen peroxide from skin, thereby helps in repigmentation. 9. Phenytoin local application: It inhibits release ofnorepinephrineandactivityofmonoamine oxidase, inhibits the production of superoxide anion and suppresses cytotoxic T- lymphocyte activity and induces type 2 like cytokine profile.
  • 160. Essentials in Dermatology152 10. Dead sea climatotherapy in combination with pseudocatalase: Here patients take bath in dead sea for 15 minutes twice daily followed by a shower to wash off salt followed by application of pseudocatalase cream prior to sun exposure. 11. Topical prostaglandin analogues (PGE2). 12. Cosmetic camouflage where nothing works or when on treatment. Systemic Therapy 1. Low dose oral corticosteroids-prednisolone 0.3 mg/kg body weight daily. 2. Oral dexamethasone or betamethasone pulse therapy- 0.5 mg/ every 5 kg body weight for two consecutive days in a week. 3. Highdosemethylprednisolonepulsetherapy- 8 mg/kg/day IV over 30 minutes for three consecutive days every 4-8 weeks. 4. Multivitamin therapy (folic acid/vitamin B12/ vitamin C). 5. Antioxidants (β-carotene, α-tocopherol, methionine, ubiquinone, vitamin C). 6. Immunomodulators- Levamisole 150 mg on two consecutive days every week; cyclo- phosphamide 50 mg twice daily; cyclosporine 6 mg/kg/day; dapsone 100 mg/day; azathi- oprine. 7. Quinoline compounds- chloroquine 250 mg/ day and hydroxychloroquine 400 mg/day. They can be combined with psoralen therapy. Phototherapy • Psoralen (stimulates melanogenesis in presence of ultra violet radiation)with ultraviolet A therapy (PUVA)- topical and systemic • Khellin + UVA (KUVA). Khellin is extracted from seeds of the plant Ammi visnaga. It can be given either topically or systemically. Khellin is given orally 50-100 mg/day, 2.5 hours prior to sun or UVA exposure up to 15 J/cm2 . But due to systemic toxicity, topical preparation of khellin is recommended. • Phenylalanine + UVA (PAUVA). Pheny- alanine both topically and systemically can be used in combination with UVA. Pheny- alanine can be used at a dose of 50-100 mg/ kg body weight 45 minutes prior to UVA exposure. • UVB radiation especially narrow band UVB • Targeted light therapy and Excimer laser (308 nm). Surgical Management Indications • Stable vitiligo (i.e. no new lesions for last two years) • Refractory to medical management. Modalities • Punch grafting • Split skin thickness graft • Blister grafting • Melanocyte culture and transplantation • Tattooing • Therapeutic spot and regional dermabrasion • Trypsinized autograft injection • Topical 5- fluorouracil combined with epidermal abrasion. For universal vitiligo options for depigmentation are: • Depigmentation with 20% monobenzyl ether of hydroquinone (for islands of residual repigmentation in extensive vitiligo). • Imatinib mesilate 400 mg/day for 15 days, then 300 mg once a day for 30 days has caused vitiligo-like depigmentation. It is a selective inhibitor of several tyrosine kinases. ALBINISM • Autosomal recessive inherited disorder. • It is characterized by reduced melanin synthesis in the melanocytes of the skin, hair, and eyes, termed oculocutaneous albinism
  • 161. Pigmentary Disorders 153 (OCA), and hypopigmentation primarily involving the retinal pigment epithelium of the eyes termed ocular albinism (OA). • Due to genetic abnormalities of melanin synthesis associated with normal number and structure of melanocytes (differentiate it from vitiligo where melanocytes are reduced or absent). • Tyrosinase-related OCA, the most common type of albinism is produced by loss of functionofthemelanocyticenzymetyrosinase resulting from mutations of the tyrosinase gene. • Affected individuals are born with white or blond hair and skin and blue eyes (Fig. 15.6). PIEBALDISM • Piebaldism is an uncommon, autosomal dominant, congenital, stable leukoderma characterizedbya whiteforelockandvitiligo- like amelanotic macules, usually containing a few normally pigmented or hyper- pigmented macules (Fig. 15.7). • Hyperpigmented macules within the amelanotic macules and on normally pigmented skin are characteristic of piebaldism. WAARDENBURG’S SYNDROME WS (Waardenburg syndrome–Hirschsprung’s disease or Shab-Waardenburg syndrome) is a rare autosomal dominant disorder that is characterized by: • Lateral displacement of the inner canthi and of lacrimal puncta • Prominence of the nasal root and of the medial eyebrows • Congenital deafness • Heterochromic irides • White forelock • Hypomelanotic macules. MELASMA (CHLOASMA) • Melasma is a common acquired hyper- melanosis that occurs exclusively in sun- exposed areas; it is exacerbated by sun exposure, pregnancy, oral contraceptives, and certain anti-epilepsy drugs. • Melasma presents in one of three usually symmetric facial patterns. The most common Fig. 15.6: Albinism—Blond hair and white skin with actinic keratosis. Fig. 15.7: Piebaldism—typical white forelock
  • 162. Essentials in Dermatology154 is a centrofacial pattern involving the cheeks (Fig. 15.8), forehead, upper lip, nose, and chin. Less common are the malar pattern, involving the cheeks and nose, and the mandibular pattern. • Successful treatment of melasma involves the triad of sunblocks, bleach and time. FRECKLE (EPHELIDES) It is an area of pale brown pigmentation usually less than 3 mm with poorly defined lateral margins • Freckle appears as result of functionally overactive melanocytes (though they are normal in number ) • They are seen only in fair skinned people • They are stimulated by ultra violet radiation and fade away during winter • Histology reveals excess of melanin pigment in the basal layer. LENTIGO (PLURAL: LENTIGINES) It is a sharply demarcated brown pigmented macule usually circular or polycyclic in shape. • Lentigo appears as a result of increased number of melanocytes in the basal layer • They do not show seasonal colour variations ( not affected by ultra violet radiation). • Histology reveals linear increase of melanocytes in the basal layer Syndromes Associated with Lentigines • LEOPARD syndrome: Lentigines (multiple), ECG abnormalities, Ocular abnormalities (hypertelorism), Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth and Deafness (sensorineural). • NAME syndrome: Nevi, Atrial myxoma, Myxoid neurofibromas and Ephelides. • LAMB syndrome: Lentigines, Atrial myxoma, Mucocutaneous myxomas and Blue nevi. PEUTZ JEGHERS SYNDROME • Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by pig- mented macules (lentigines) of the buccal mucosa, lips, fingers, and toes and by gastrointestinal polyps. • It is caused by mutations in a novel serine threonine kinase, and its gene has recently been mapped to chromosome 19p. • The pigmented macules (dark brown or blue- brown) are most common on the buccal mucosa and lips, but also seen over palate and tongue. The macules on the skin are usually foundontheface(aroundthemouthandeyes), dorsa of the hands and feet and perium- bilically. • The diagnosis is particularly important because of the presence of gastrointestinal polyps, which are most frequent in the small bowel, particularly the jejunum, which may manifest with gastrointestinal bleeding. Malignant change may occur in these polyps. Fig. 15.8: Melasma—hyperpigmented light brown macules over the cheeks
  • 163. Pigmentary Disorders 155 • Any child with recurrent, unexplained abdominal pain should be examined for the typical mucosal, and periorificial pigmented lesions of Peutz-Jeghers syndrome. DRUGS CAUSING HYPERPIGMENTATION • Generalized–Addisonian-like occurs with ACTH and generalized diffuse due to clofa- zimine, cyclophosphamide, minocycline, etc. • Localized: – Melasma- like- estrogen, progesterone, phenytoin – Knuckle pigmentation- bleomycin – Palmoplantar- cyclophosphamide, doxo- rubicin – Linear – bleomycin (flagellate), zido- vudine.
  • 164. Essentials in Dermatology156 ICHTHYOSIS Ichthyosis (from Greek ichthys “fish”) denotes a group of hereditary and acquired disorders of keratinization characterized by the development of dry rectangular scales. Hereditary (Inherited) Ichthyoses Ichthyosis Vulgaris It is a common autosomal dominant disorder characterized by mild scaling on extensor aspect of the limbs (Fig. 16.1), more than trunk and spares the flexures. Increased palmar markings or frank palmoplantar keratoderma may be associated features. Onset is after 3 months of age. Scaling gets worse in winter. Differential diagnosis: Atopic xerosis, eczema craquele, acquired ichthyosis, and Refsum’s disease. X-linked Recessive Ichthyosis It appears in infancy and occurs in males. Females may be heterozygotes and female carriers are eithertotallysparedoronlymildlyaffected.Large dirty brown scales characterize it. Extensor and flexor aspects of the limbs are involved but spare rhomboidal spaces in body folds (Figs. 16.2 and 16.3). Palms and soles are spared but the neck, 16 Keratinization Disorders side of the face and trunk are affected. This form of ichthyosis is associated with steroid sulphatase deficiency. Differential diagnosis: In contrast to ichthyosis vulgaris, no hyperlinear palms, no keratosis pilaris, flexural involvement and larger, darker scales. Fig. 16.1: Ichthyosis vulgaris—scaling limited to extensor aspects of limbs (shin)
  • 165. Keratinization Disorders 157 Lamellar Ichthyosis Lamellar ichthyosis is a rare form of ichthyosis, which presents at birth as “Collodion baby”; baby is encased in a taut inelastic membrane. In this autosomal recessive disorder, the baby later develops large, thick plate like scales all over the body including flexures. Facial involvement often results in ectropion and eclabium (Figs 16.4, to 16.6). Differential diagnosis: Includes X-linked recessive ichthyosis and ichthyosiform eythrodermas with collodion presentation. Figs 16.2 and 16.3: X-linked recessive ichthyosis—large dirty brown scaling involving flexor and extensor aspects of limbs and trunk but sparing rhomboidal spaces in body folds Fig. 16.4: Lamellar ichthyosis—face involvement by erythema and scaling Fig. 16.5: Lamellar ichthyosis—brownish plate like scales over the trunk Fig. 16.2 Fig. 16.3
  • 166. Essentials in Dermatology158 Fig. 16.6: Lamellar ichthyosis—large plate like scales involving lower legs Figs 16.7 and 16.8: Bullous congenital ichthyosiform erythroderma—no more blisters seen, body folds show thick dark gray brown scales forming warty, ridged pattern Fig. 16.9: Bullous congenital ichthyosiform erythroderma—palms involved by keratoderma Congenital Ichthyosiform Erythroderma It is of two types: 1. Bullous congenital ichthyosiform erythro- derma: It is inherited as an autosomal dominant trait. At birth, the skin is erythematous, moist and tender. Blisters developatorshortlyafterbirthandlater,thick dark gray brown scales form warty-ridged pattern (Figs 16.7 and 16.8). There is accentuation in the areas of flexures and on the palms and soles (Fig. 16.9). Normal appearing skin within a hyperkeratotic area is a valuable diagnostic sign. Skin colonization by Staphylococcus brevibacterium and possibly fungi produces a distinctive and embarrassing body odor. Ectropion and deformed ears are common. Differential diagnosis: At birth, may be confused with epidermolysis bullosa, staphylococcal scalded skin syndrome, herpetic infections and incontinentia pigmenti. In older patients, ichthyosis hystrix, ichthyosis bullosa of Siemens, and non- epidermolytic epidermal naevi may resemble bullous congenital ichthyosiform erythroderma. 2. Nonbullous congenital ichthyosiform erythroderma: It is an autosomal recessive disorder. Most infants with it are born as Fig. 16.7 Fig. 16.8
  • 167. Keratinization Disorders 159 collodion baby. As the membrane is cast off in 10 to 14 days, generalized erythema and scaling are apparent. Scales may be large and plate like on the legs but are apt to be fine on the trunk, face and scalp. It has a tendency to improve at the time of puberty. Ectropion, deformities of the ears and sparsity of the scalp hair are common accompaniments. Differential diagnosis: Congenital infections such as candidiasis, congenital psoriasis, Netherton’s syndrome, immunodeficiency disorders, trichothiodystrophy and neutral lipidstoragediseasemaymimicthecutaneous signs of non-bullous ichthyosiform erythroderma. • A collodion baby is the usual presentation of congenital recessive ichthyosis. Kollodes is the Greek word for glutinous or glue like. The child is born encased in a transparent, parchment-like membrane, which is taut and may impair respiration and sucking. Collodion presentation can develop into a wide spectrum of ichthyosis phenotypes as the child grows. Differential diagnosis: Harlequin fetus can be easily differentiated from collodion baby. Restrictive dermopathy or “Stiff baby syndrome” produces a generalized taut thick, tethered and unyielding skin at birth which does not desiccate in the neonatal period. Infective causes of desquamation such as staphylococcal scalded skin syndrome should be included in differential diagnosis. • Harlequin ichthyosis (fetus) is a dramatic, severe, and usually fatal presentation of ichthyosis. The child is often premature and born with massive, shiny plates of stratum corneum separated by deep, red fissures that tend to form geometric patterns. There are poorly developed or absent ears and marked ectropion and eclabium. These children are at great risk during the neonatal period and often die shortly after birth. Differential diagnosis: As given for collodion baby. A variant of infantile systemic hyalinosis and the stiff skin syndrome (congenital fascial dystrophy) also present with tight skin. Ichthyosiform Syndromes 1. Refsum’s syndrome (Heredopathia atactica polyneuritiformis) • Refsum’s syndrome is a rare autosomal recessive metabolic disorder in which there are characteristic neurological and cutaneous clinical features: • The underlying abnormality is deficiency of enzyme phytanic acid oxidase. • As a consequence of this deficiency, phytanic acid (found in green vegetables) accumulates and displaces some of the unsaturated fatty acids, such as linolenic acid, from the lipids through out the tissues. • It manifests usually in the second decade. • Skin is affected by an ichthyosis very similar to ichthyosis vulgaris. • Neurological changes include a cere- bellar degenerative disorder (cerebellar ataxia), a progressive polyneuropathy, retinitis pigmentosa, and a sensory deafness. Rarely, cardiac abnormalities have been described. • Diagnosis—Histopathology of the skin shows some of the epidermal cells containinglipid vacuoles. No or very little phytanic acid is present in the blood. • Treatment by a phytanic acid free diet, in which green vegetables and dairy products are excluded, has been used. 2. Sjögren’s-Larsson syndrome: • This uncommon neuroectodermal genodermatosis appears to be inherited as an autosomal recessive disorder. • The underlying metabolic defect is deficiency of enzyme fatty alcohol: nicotinamide-adenine dinucleotide oxidoreductase.
  • 168. Essentials in Dermatology160 • The skin disorder becomes evident after the first few months of life with scaling over the body and hyperkeratosis of palms and soles. • The neurological component usually starts at 2-3 years of life and remains static after puberty, consists of a spastic diplegia (Fig. 16.10), or occasionally a tetraplegia with mental retardation. Other features are seizures and degeneration of retina. • Diagnosis—Histopathological changes are similar to lamellar ichthyosis. • Treatment—Diet lacking natural fat and containingmediumchaintriglycerideshas been beneficial. 3. KID syndrome: • The acronym KID—Keratitis, Ichthyosis, and Deafness describes the salient clinical features of this syndrome. 4. Netherton’s syndrome: • It is a rare autosomal recessive disorder characterized by concurrence of ichthyosis linearis circumflexa, trichorrhexis invaginata (bamboo hair) and atopic dermatitis. 5. CHILD syndrome: • The acronym CHILD describes a very rare disorder comprising Congenital Hemidy- splasia with Ichthyosiform erythroderma and unilateral Limb Defects mainly skeletal hypoplasia. 6. IBIDS syndrome (Tay’s syndrome): • The acronym IBIDS describes Ichthyosis, Brittle hairs, Impaired intelligence, Decreased fertility and short Stature. Acquired Ichthyoses The distinction between dry skin (xerosis) from environmental causes and acquired ichthyoses is sometimes difficult. The sudden onset of generalized pronounced ichthyoses in an adult could be due to: 1. Lymphomas especially Hodgkin’s lymphoma 2. Internal malignancy 3. Malabsorption syndromes and malnutrition 4. Certain drugs like clofazimine 5. Hypothyroidism 6. Lepromatous leprosy 7. HIV disease. Treatment • Emollients for scaly skin especially after bath • Salicylic acid, urea, lactic acid in ointment formorpropyleneglycol-glycerine–lacticacid mixture for topical application • Oral retinoids – Etretinate or Acitretin. They are really useful in lamellar and congenital ichthyosiform erythrodermas. DARIER’S DISEASE • It is disorder of keratinization with an autosomal dominant mode of inheritance (chromosome 12). • Onset is during puberty when dirty, warty, greasy papules appear in the seborrheic distribution (Figs 16.11 to 16.13) • In due course of time, the lesions grow in size and form malodorous, papillomatous and vegetative growths Fig. 16.10: Sjögren's-Larsson syndrome—child having spastic diplegia with ichthyosis
  • 169. Keratinization Disorders 161 Figs 16.11 and 16.12: Darier's disease—dirty, warty greasy papules in seborrheic distribution over the trunk Fig. 16.13: Darier's disease—dirty, warty greasy papules in seborrheic distribution over the scalp and face • Other features include palmar pits (Fig. 16.14) and ‘V’ shaped nicking of nails. • Oral cavity shows cobble stone appearance of the mucosa (Fig. 16.15). • Acral areas may demonstrate dome shaped papular lesions known as acrokeratosis verruciformis of Hopf (Figs 16.16 and 16.17) • Exacerbation occurs following sun exposure • Histopathology shows dyskeratosis (corps ronds and grains) and acantholysis. Differential diagnosis: Well developed cases distinctive; early lesions confused with other follicular keratoses. Same histologic picture can be seen in Grover’s disease as well as epidermal naevi and acquired acanthomas, so clinico pathologic correlation required. Treatment: Acitretin 25-50 mg daily is probably the best treatment; should be used until disease brought under control and then stopped if side- effects develop. Topical retinoids and keratolytics Fig. 16.11 Fig. 16.12
  • 170. Essentials in Dermatology162 Fig. 16.14: Darier's disease—palmar keratoses with pits Fig. 16.15: Darier's disease—cobblestone appearance of hard palate mucosa Figs 16.16 and 16.17: Darier's disease—acrokeratosis verruciformis of Hopf lesions over the dorsa of hands are disappointing at best. Some patients improve dramaticallywithantibiotics.Avoidsunexposure and use sun screens. POROKERATOSIS • It is a chronic progressive disease which occursduetoabnormalproliferationofaclone of keratinocytes. • Porokeratosis of Mibelli is the most common prototype of porokeratosis • The lesions are slightly atrophic plaques surrounded by elevated keratotic wall with a furrow(seensometimes)(Figs16.18and16.19) • Various types of porokeratosis are porokeratosis of Mibelli, disseminated superficial actinic porokeratosis, palmo- Fig. 16.16: Fig. 16.17
  • 171. Keratinization Disorders 163 plantar porokeratosis, porokeratosis palmoplantaris et disseminata and linear porokeratosis (Fig. 16.20). • Histological hallmark is the column of parakeratosis known as ‘cornoid lamella’. Differential diagnosis: Multiple lesions can be mistaken for psoriasis, lupus erythematosus, pityriasis rubra pilaris or verrucous lichen planus. Solitary lesions often misinterpreted as tinea, warts, or actinic keratoses. Palmoplantar lesions are hard to diagnose clinically; one can consider Fig. 16.18: Porokeratosis of Mibelli—an atrophic plaque surrounded by elevated keratotic wall with a furrow Fig. 16.19: Porokeratosis of Mibelli—ridge made prominent by gentian violet paint Fig. 16.20: Linear porokeratosis— involving the arm punctate palmoplantar keratoderma, arsenical keratoses and warts; only biopsy provides the answer. Treatment: Cryotherapy, CO2 and pulsed dye laser therapy or other destructive methods can be used for limited lesions. Porokeratosis is usually resistant to treatment but in some cases retinoids (acetretin) or PUVA have been used with success. PALMOPLANTAR KERATODERMA (PPK) Palmoplantar keratoderma means thickening of palms and soles. They can inherited as well as acquired. Inherited PPK can be classified based on the presence or absence of transgradiens (spreading of keratoderma on to the extensor surface). • Transgradiens is seen in Mal de Meleda, Vohwinkel’s, Greither’s and Papillon-Lefevre syndrome. • Transgradiens is not seen in Thost-Unna (most common diffuse palmoplantar keratoderma), Vorner (diffuse PPK with epidermolytichyperkeratosis)andfocaltypes. • The important features of various inherited PPK are given in the following table.
  • 172. Essentials in Dermatology164 Type of keratoderma Important features Thost –Unna (AD) Diffuse PPK with livid red border (Fig. 16.21) Marked hyperhidrosis Vorner type (AD) Diffuse PPK similar to Thost –Unna type.Histology shows epidermolytic hyperkeratosis Vohwinkel’s type (AD) Honey combed palmoplantar thickening with constriction bands and mutilation, star fish shaped keratosis on dorsa of hands and fingers (Fig. 16.22) Mal de Meleda (AR) Palmoplantar keratoderma in a glove like distribution. Erythema is prominent with hyperhidrosis and malodor Greither (AD) Diffuse PPK that is progressive. Extensor surfaces of hands, knees and elbows shows psoriasiform plaque (Fig. 16.23) Olmsted syndrome (S) Congenital PPK with perioral hyperkeratosis. Spontaneous amputation can occur Papillon-Lefevre (AR) PPK associated with periodontosis and increased frequency of pyogenic infection Note: AD—Autosomal dominant, AR—Autosomal recessive, S—sporadic occurrence Fig. 16.21: Palmoplantar keratoderma—diffuse keratoderma localized to palms Fig. 16.22: Palmoplantar keratoderma—leading on to mutilation Fig. 16.23: Palmoplantar keratoderma—extending onto dorsa of hands and feet (transgradien palmoplantar keratoderma) • Othertypesofpalmoplantarkeratodermasare focal kertodermas, striate keratodermas and puntate keratodermas (Fig. 16.24). • Various causes of acquired keratoderma are pityriasis rubra pilaris, malignancy (Tylosis), myxedema, Darier’s disease, keratoderma climactericum, psoriasis, lichen planus, and tinea pedis. Treatment: Topical keratolytics, vitamin D3 analogues and mechanical debridement useful. Some cases respond to oral isotretinoin.
  • 173. Keratinization Disorders 165 ACANTHOSIS NIGRICANS Acanthosis nigricans is a nonspecific reaction pattern involving major body folds and mucocutaneous regions characterized by hyperpigmented, velvety, soft, verrucous lesions in a symmetric fashion (Fig. 16.25). • It is broadly divided into benign and malignant form. • Benign acanthosis nigricans involves limited body areas and is less severe than malignant forms. • The various benign forms that are the most common include benign familial acanthosis nigricans, acanthosis nigricans associated with various syndromes, endocrine disease (especially insulin resistance diabetes mellitus, HAIR-AN syndrome [Hyper Androgenism, Insulin Resistance, and Acanthosis nigricans]), obesity (pseudo- acanthosis Nigricans) and drugs (Nicotinic acidic, fusidic acid, stilbestrol, oral contraceptives, triazinate). Fig. 16.24: Punctate keratoderma—punctuate keratotic lesions involving palmar creases Fig. 16.25: Acanthosis nigricans—hyperpigmented, velvety, soft, verrucous involvement of neck • Malignant acanthosis nigricans is associated with extensive, widespread lesions and mucosal involvement. They may precede, follow or occur simultaneously with onset of malignancy. Thickening of palms, especially fingertips produces accentuated dermato- glyphics with deep sulci called as Tripe palms. • Gastric carcinoma is the most commonly associated tumor; other sites include the bronchus, pancreas, ovary, bile duct, gallbladder,endometrium,breastandthyroid. Differential diagnosis:Confluent and reticulated papillomatosis, tinea versicolor, X-linked ichthyosis, retention hyperkeratosis, dirty neck of atopic dermatitis. Treatment: As it is a reaction pattern to some of the underlying conditions, treatment need to be directed at them. Topical retinoids may bring modestimprovement.
  • 174. Essentials in Dermatology166 17 Urticaria, Angioedema and Pruritus URTICARIA AND ANGIOEDEMA Urticaria Is a dermal vascular reaction of the skin characterized by the appearance of itchy wheals, which are elevated (edematous), pale or erythematous, transient and evanescent plaque lesions. These lesions usually do not last beyond 24 hours. They change in size and shape by peripheral extension or regression during few hours (Figs 17.1 and 17.2). Wheals itch. The intensity of itch varies. Angioedema (Quincke’s Edema) Is also a vascular reaction, which involves subcutaneous or submucosal tissues (rather than dermis in urticaria) so skin overlying the swelling Figs 17.1 and 17.2: Urticaria—showing itchy erythematous wheals of various shapes and sizes Fig. 17.1 Fig. 17.2
  • 175. Urticaria, Angioedema and Pruritus 167 is normal in color and margins of swelling are indistinct (diffuse swelling). It commonly results in asymptomatic swelling of the lips (Fig. 17.3), eyelids,etc.Duetolaryngealinvolvement,patient may develop respiratory distress. Gastro- intestinal involvement may cause vomiting and abdominal pain. Angioedema may be classified into hereditary angioedema [Type I (85%)-C1 esterase inhibitor absent, Type II (15%)-C1 esterase inhibitor not functional] and acquired angioedema (Acute angioedema due to allergic IgE mediated, e.g. due to drugs, food, insects, contact dyes, serum sickness, cold urticaria or Chronic recurrent angioedema-(Idiopathic in most cases; rarely due to acquired C1 esterase inhibitor deficiency). Urticaria may be acute or chronic Acute Urticaria Means urticaria of less than 6 to 8 weeks duration. Common causes are drugs especially penicillin, foods, especially shell fish, and rarely infections. In India, insect bites are another important cause. No apparent cause can be found in at least half of acute attacks. Even if a cause can be identified and withdrawn, it is often several days before the urticaria subsides. Chronic Urticaria If urticaria lasts for more than 6 to 8 weeks duration, it is called chronic urticaria. Culprit in the great majority of cases remains obscure. Up to 55% of patients with chronic idiopathic urticaria possess functional IgG antibodies directed against the high affinity IgE receptors or less commonly against IgE itself. These auto- antibodies release histamine from human skin mast cells and blood basophils and appear to be the cause of the disease (autoimmune urticaria). Immunoglobulin and complement components may be deposited perivascularly, and can be visualized by direct immunofluorescence examination. Basic pathogenic mechanisms of urticaria are immune and nonimmune mechanisms. Immune mechanism consists of type I hypersensitivity mechanism (IgE mediated), through complement activation, immune complex mechanism, or autoimmune process. Nonimmune mechanism works through direct release of histamine and various mediators from mast cells, vasoactive stimuli, aspirin, dietary pseudoallergens and due to angiotensin converting enzyme inhibitors. Etiological Factors(6 I’s + others ) 1. Ingestants a. Foods – cheese, eggs, nuts, fish, mush- rooms, etc. b. Food additives – tartarzine dyes, etc. c. Food preservatives d. Drugs – penicillin, salicylates, sulphon- amides, etc. 2. Injectants a. Insect bites b. Injection – drug, sera, blood, etc. 3. Inhalants • Pollens, animal dander, etc. 4. Infestation by parasites • Amoebiasis • Giardiasis Fig. 17.3: Angioedema—swelling of chin and lip of sudden onset
  • 176. Essentials in Dermatology168 Fig. 17.4: Dermographism–stroking the skin with blunt metallic instrument resulted in an exaggerated triple response forming wheals along them Fig. 17.5: Cold urticaria—ice cube test producing urticaria • Hookworm • Round worm. 5. Infection –focus in teeth, tonsils, sinuses or elsewhere. 6. Implants—prosthetic and hormonal 7. Physical causes/factors (Urticarial attacks are brief lasting for 30 to 60 minutes): a) Dermographism(write-on-skin)–stroking the skin with blunt metallic instrument results in an exaggerated triple response (Fig. 17.4). b) Pressure urticaria–pressure c) Cholinergic urticaria–increase in core body temperature (manifest as small intensely pruritic papules) d) Cold urticaria–cold air or water (Fig. 17.5) e) Heat urticaria–heated object f) Solar urticaria–sun exposure g) Exercise induced–exercise h) Aquagenic pruritus/urticaria–contact with water i) Vibratory urticaria–handling vibratory instruments. 8. Contact urticaria – Contact urticaria refers to a wheal and flare reaction following external contact with a substance, e.g. on coming in contact with potato, onion, nitrogen mustard, etc. develops urticaria at site of contact. It usually appears within 30 minutes and clears completely within hours without residual signs of irritation. 9. Rule out underlying collagen vascular disorders, malignancy or any psychogenic cause. 10. Chronic idiopathic urticaria (CIU), defined as theoccurrenceofdaily,oralmostdaily,wheals and itching for at least 6 weeks, with no obvious cause. Idiopathic – no cause found. Fig. 17.6: Proceeding in a case of urticaria
  • 177. Urticaria, Angioedema and Pruritus 169 Diagnosis How to proceed in a case of urticaria? 1. Urticaria due to physical causes or drugs excluded by history and examination (Fig. 17.6). 2. Complete food elimination followed by gradual introduction of one dietary element at a time helps in detection of food induced urticaria. 3. Mask use/nasal filter use/change of place may work for inhalants. 4. Stool examination by concentration method on 3 consecutive days – infestations are detected and treated accordingly. 5. Look for a focus of infection. If not possible to detect, give a course of antibiotics. Still no response, change the antibiotic. 6. The major advance in our understanding of chronic idiopathic urticaria (CIU) in recent years has been the discovery that in 30-50% of patients with so labeled chronic idiopathic urticaria, the disease is due to an autoimmune process, and therefore is not strictly ‘idiopathic’. 7. The autologous serum skin test is a useful screening test for autoimmune chronic urticaria (AICU). In this test, 0.05 ml of the patient’s serum, removed during a period of disease activity, is injected intradermally into the same patient’s uninvolved forearm skin, along with equal volumes of saline and histamine (10 µg/ml) at adjacent sites. The test is read 30 min later. A positive result is recorded if the diameter of the wheal at the serum-injected site is 1.5 mm greater than that of the bleb at the saline-injected site. The sensitivity and specificity of the test are 65-81% and 71-78%, respectively. Patients with AICU are more treatment-resistant, and their disease runs a more aggressive course, than those with non-autoimmune CIU. 8. If still getting urticaria, then look for other causes and treat symptomatically. Differential Diagnosis of Urticaria Includes all dermatologic conditions with an urticarialcomponentlikecutaneousmastocytosis, urticarial vasculitis, insect bite reactions (papular urticaria), acute febrile neutrophilic dermatosis, pre bullous pemphigoid, acute facial contact dermatitis, erythema multiforme, collagen vascular disease, porphyria, pityriasis rosea, psoriasis and last but not least scabies. Differential Diagnosis of Angioedema Infections (cellulitis), trauma, superior vena cava syndrome, subcutaneous emphysema, Melkersson –Rosenthal syndrome. Treatment Acute urticaria • Minimize heat and stress, • Avoid alcohol, NSAIDs and opiates. • Soothing lotions such as calamine for topical application given during attack of urticaria. • Antihistaminics: H1 antagonists or H2 antagonists or Both together Old sedative antihistaminics are still better during acute episodes. • Corticosteroids may be required to tide over a crisis-tapering regime commencing with 30 mg prednisolone daily, with or without concurrent H1 antagonist administration. • Adrenaline used in anaphylaxis. • Other measures like intravenous fluids, oxygen use may be required. Chronic Urticaria • Antihistamines still remain the mainstay of drug treatment. • Doxepin 25 to 50 mg at night time may be added. • Corticosteroids-occasionally as short tapering courses given in autoimmune chronic
  • 178. Essentials in Dermatology170 urticarias as they fail to respond to antihistamines. • Cyclosporine-2.5 to 5 mg /kg body weight/ day is another option. Control of urticaria usually occurs within 1 week of commencing treatment. • Intravenous immunoglobulin. • Other drug treatments are ketotifen (1-2 mg dailyoratnight),disodiumcromoglycate,beta agonist (terbutaline 2.5 mg three times daily), calcium channel blockers (nifedipine), leukotriene antagonists (montelukast, zileuton), and anti IgE monoclonal antibody. PRURITUS (ITCHING) Pruritus may be defined simply as that unpleasant sensation which produces the desire to scratch. It may be localized or generalized. If generalized,needsinvestigationsforanysystemic cause. Certain areas of the skin, particularly susceptible to pruritus are ear canals, perianal and genital areas, eyelids, etc. Localized pruritus may give clues to the etiology and is less likely to be associated with widespread or systemic disease. In the scalp, pruritus may be due to psoriasis or an ongoing folliculitis, in the inguinal oranalregionduetopruritusani,pruritusvulvae, pruritus scroti, venereal diseases, ectoparasites (scabies, pediculosis), in the hands and feet due to psoriasis, pompholyx, contact dermatitis, in the mid back due to notalgia paresthetica, macular amyloidosis, and in the lower limbs in older patients due to asteatosis. Causes of pruritus can be classified as follows: 1. Dermatological disorders 2. Systemic diseases 3. Psychogenic pruritus 4. Iatrogenic pruritus. Dermatological Disorders Common dermatoses known to produce pruritus are scabies, pediculosis, insect bites, eczema, urticaria, prickly heat, lichen planus, dermatitis herpetiformis, bullous pemphigoid, psoriasis, seborrhoeic dermatitis, dermatophytosis (tinea), urticaria pigmentosa, varicella and rubella, papular and pruritic eruption seen in AIDS patients, etc. Systemic Disorders Three important systemic disorders most likely to play role in acquired acute pruritus are renal disease, hepatic disease and abnormalities of the hematopoietic system. • Renal – chronic renal insufficiency • Hepatic – intrahepatic and extrahepatic biliary obstruction (cholestasis). • Abnormalities of the hematopoietic system – iron deficiency anemia, polycythemia vera (is associated with bath pruritus), leukemia, Hodgkin’s lymphoma, mycosis fungoides, mast cell disorders. • Endocrine – diabetes mellitus, myxoedema, hyperthyroidism, hypoparathyroidism. • Intestinal parasites – infestation with hookworm, round worm, pin worm. • Collagen vascular disorders – SLE, sicca syndrome. • Neurological –multiplesclerosis,braintumor. • Pregnancy. Psychogenic Pruritus Psychosomatic disorders resulting in itch commonly occur in the middle aged or older individuals. Iatrogenic Pruritus Commonly induced by opium alkaloids, CNS stimulants, antidepressants, and belladona alkaloids. Diagnosis History and clinical examination is of paramount importance. In addition, investigations outlined
  • 179. Urticaria, Angioedema and Pruritus 171 below may be undertaken to find the underlying cause. 1. Hemogram including ESR. 2. Liver function tests. 3. Kidney function tests. 4. Urine examination for albumin, sugar and cells. 5. Blood sugar. 6. Stool examination for occult blood, worms and ova. 7. Chest X-ray. 8. Thyroid function tests. 9. Hepatitis C screening. 10. HIV testing. 11. Uric acid estimation and also acid phos- phatases. 12. Skin biopsy for mast cells and immuno- fluorescence. 13. Patch testing, photopatch testing, immuno- globulin levels. 14. Screening for underlying malignancy. 15. Serum protein electrophoresis. Treatment 1. Eliminate causative disease if possible or treat it appropriately. 2. Avoid provocative influences: • Friction from rough clothing. • Overheating and vasodilatation, e.g. alcohol, hot drinks. • Keep nails short. • Soothing lotions, e.g. calamine in urticaria, moisturisers for dry skin. • Occlusive bandaging may be done to retain moisture in the skin. • Emollients of bland nature, e.g. coconut oil, liquid paraffin. • 1% menthol in 90% ethanol is of significant value. • Steroid creams. • Topical antipruritic drugs, e.g. doxepin, crotamiton. • Avoidance of strong soaps in elderly individuals. 3. Systemic treatment: Antihistamines: H1 antagonists-especially sedative ones may be preferred Systemic steroids: Sometimes required to control urticaria Doxepin 4. Specific treatments: For uremic pruritus- Naltrexone (50 mg oral daily), activated charcoal, UVB phototherapy,ondansetron(4mgtwicedaily), cholestyramine For cholestatic pruritus- cholestyramine, phenobarbitol, UVB phototherapy, rifampicin (300-450 mg daily), naltrexone (50 mg oral daily), and danazol. For hematologic disease-cimetidine, cyproheptadine, pizotifen (0.5 mg three times daily), danazol, interferon alpha 2b, UVB phototherapy, iron replacement therapy. Lidocaine and intralesional steroids (for localized pruritus and trigger points) may be tried as last resort.
  • 180. Essentials in Dermatology172 18 Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis DRUG ERUPTIONS • A drug may be defined as a chemical substance, or combination of substances, administered for the investigation, prevention or treatment of diseases or symptoms, real or imagined. • Drug eruptions are some of the most common skin disorders. • They are seen in 2 to 3% of hospitalized patients. • These eruptions may closely mimic other skin disorders. Characteristics of Drug Eruptions 1. There is a history of drug intake preceding the eruption. The history of drug intake must include all systemic drugs, nonprescription drugs, home remedies and topical medications. A previous history of allergic reaction may increase the risk of development of an allergic reaction. 2. Drug eruption is sudden in onset. 3. Generalized eruption is often pruritic. 4. Eruption is bilateral and symmetrical, exception to this is fixed drug eruption. 5. Regression of eruption occurs on withdrawal of drug. 6. Similar type of rash recurs on re-exposure to the same or similar drug. Undesirable cutaneous or mucocutaneous reactions to systemically absorbed drugs occur through two mechanisms. 1. Immune mechanisms: All the four hypersensitivity mechanisms may be involved. Type I – IgE dependent reactions cause urticaria, pruritus, bronchospasm and laryngeal edema within minutes, hours or days. Type II – Cytotoxic reactions may cause thrombocytopenia. Type III – Immune complex dependent reactions result in serum sickness, urticarial or leukocytoclastic vasculitis within a week or so. Type IV – Cell mediated immune response may lead to eczematous and other types of eruptions in 3 to 4 weeks time. 2. Non-immune mechanisms: They include drug induced hemolysis (G6PD deficiency), mast cell degranulation (codeine, radiocontrast media), exacerbation of disease (psoriasis by lithium or beta blocker), drug deposition in skin, alopecia, etc.
  • 181. Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome 173 General Rules • Drug allergy is most frequent in older individuals and may be related to development of immune response and increased exposure to drugs. • Topical application of drugs has the greatest propensity to induce allergy, followed by the intravenous route and the oral route. • The drugs most often responsible for the eruptions are antimicrobials and antipyretic/ anti-inflammatory analgesics. • The appearance of the eruption may provide some clues to its cause (e.g. fixed drug eruptions associated with sulphonamides). • Always keep in mind the fact that drug eruptions are great imitators of other skin diseases. • The most common morphologic patterns of drug eruptions are exanthematous (40%), along with urticaria and/or angioedema (37%), fixed drug eruption (6%), erythema multiforme and others. Types of Drug Eruptions 1. Exanthematous eruptions (Maculopapular eruptions) (occur within 1 week). 2. Urticarial eruptions. 3. Serum sickness. 4. Acneiform eruptions (Fig. 18.1). 5. Drug hypersensitivity syndrome. 6. Lupus like eruptions. 7. Lichenoid eruptions. 8. Pityriasis rosea like eruptions. 9. Phototoxic (Fig. 18.2)and photoallergic eruptions. 10. Vesicobullous eruptions. 11. Eczematous eruptions. 12. Alopecia. 13. Skin pigmentation. 14. Vasculitic eruptions. 15. Fixed drug eruptions. 16. Erythroderma. 17. Erythema multiforme. 18. Stevens-Johnson syndrome. 19. Toxic epidermal necrolysis. Exanthematous eruptions: These are the most frequent of all cutaneous reactions to drugs, and usually appear within 1 week of the causative drug being started. A rash may also start within 4-7 days of the offending drug being stopped. Lesions most often start first and clear first from head and upper extremities. They may be accompanied by fever, pruritus and eosinophilia. Antibiotics especially semisynthetic penicillins and sulfonamides are the most common causes of this reaction pattern. Fig. 18.1: Acneiform drug eruption— monomorphous papular eruption over the back Fig. 18.2: Phototoxic drug eruption—exaggerated sunburn reaction limited to exposed areas
  • 182. Essentials in Dermatology174 Urticarial eruptions: It is the second most common type of cutaneous drug eruption. Angiotension converting enzyme inhibitors are the frequent causes of angioedema often without urticaria. Serum sickness-like reaction: Serum sickness- like eruption consists of fever, a rash with usually urticarial features and arthralgias occurring within 1 to 3 weeks of initiation of the drug. Lymphadenopathy and eosinophilia may also be found. Drug hypersensitivity syndrome (DHS): Also known as drug rash with eosinophilia and systemic symptoms (DRESS) syndrome or as drug induced delayed multiorgan hypersensitivity syndrome (DIDMOHS). It consists of an exanthema, hepatitis and fever. Eighty percent of the cases have an exanthem type eruption whereas others will develop more serious Stevens Johnson syndrome. DHS may be life threatening and requires prompt discontinuation of the drug and systemic corticosteroids. Fixed drug eruption: It differs from other eruptions in that it occurs and then recurs at fixed sites. Single or multiple circular or oval erythematous macule/s or plaque/s develop with burning or stinging sensation (Fig. 18.3). These lesions sometime develop into bullous lesions (Fig. 18.4) and when they heal leave behind slate gray colored pigmentation (Fig. 18.5). Mucocutaneous junctions are commonly affected. Erythroderma: It is a generalised erythema, infiltration and scaling of the skin (involving more than 90% of the surface area of the body). It may be a manifestation of a drug eruption but usually occur due to dermatological disorders like psoriasis, contact dermatitis, pityriasis rubra pilaris, etc. Fig. 18.3: Fixed drug eruption—typical slate grey oval macule with halo of erythema over the trunk Fig. 18.4: Fixed drug eruption–circular, slate gray colored pigmented macular lesion developing bullae over it Fig. 18.5: Fixed drug eruption—multiple fixed drug eruptions over the chest
  • 183. Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome 175 Erythema multiforme: Erythema multiforme is characterized by many types of lesions including urticaria, target lesions (iris lesions or bull’s-eye lesions) (Figs 18.6 and 18.7) and vesicles and bullae, bilaterally symmetrically over acral areas of the body. They may also involve mucous membranes. Stevens-Johnson syndrome: It is a severe form of erythema multiforme associated with constitutional symptoms (fever) and visceral organ involvement, e.g. kidneys. The skin as well as mucous membranes are both involved (Figs 18.8 and 18.9). Toxic epidermal necrolysis (TEN): The term toxic referred to a presumed toxin responsible for the prodrome and the eruption, epidermal to the presence of significant epidermal damage and necrolysis to the pathologic findings of necrosis and clinical findings of epidermolysis. It is a potentially life threatening, severe mucocutaneous reaction pattern characterized by fever, systemic toxicity, erythema and tenderness of skin followed by flaccid bullae formation resembling a burns case (Fig. 18.10). Nikolsky’s sign is positive. Mortality from TEN is 11 to 33%. Fig. 18.6: Erythema multiforme—chest showing typical target lesions Fig. 18.7: Erythema multiforme—target lesions showing three zones of color Fig. 18.8: Stevens-Johnson syndrome—facial eruption with hemorrhagic crusting of lips Fig. 18.9: Stevens-Johnson syndrome—atypical target lesions over the back
  • 184. Essentials in Dermatology176 Diagnosis Diagnosis is basically based on suspicion and history of drug intake. A thorough and stepwise approach is essential to proper diagnosis of a drug- induced skin reaction. First step in patient evaluation should include (1) a comprehensive drug history, (2) awareness of various clinical manifestations of drug allergy and cutaneous reaction, (3) awareness of factors that favor development of allergic reactions to drugs, and (4) awareness of the immunologic and nonimmunologic mechanisms involved in cutaneous reaction to drugs. A general rule of thumb is that drugs started within one week of the onset of the eruption are the most likely suspects. Second step is skin biopsy and in vivo testing. This includes patch testing, scratch/ prick testing and dechallenge/ rechallenge tests. Dechallenge/ rechallenge continues to be regarded as the most definitive method for ascertaining drug-induced reactions. However, it is often not an option if the patient has experienced a life threatening condition or if suspected agent cannot be continued. Blood work-up may also aid in the clinical diagnosis. A CBC with differential count may show atypical lymphocytosis, leukopenia, leukocytosis, eosinophilia and so on. Liver function tests, serum creatinine, urinanalysis and TSH may be indicated in patients with suspected drug induced hypersensitivity syndrome. Third step is the invitro testing which include Radio Allergosorbent Assays (RAST) and Enzyme Linked Immunosorbent Assays (ELISA). Other tests include Lymphocyte Transformation Test (LTT), Macrophage migration Inhibition Factor (MIF), Lymphocyte Toxicity Assay (LTA), Basophil Degranulation Test and Histamine Release tests. Differential Diagnosis Consider differential diagnoses such as infections, collagen vascular disease, primary skin conditions and neoplasia. Culture of skin, blood, tissue, erythrocyte sedimentation rate, ANA, and other tests may be ordered to help confirm or rule out other conditions. If palpable purpuric lesions are present, a complete physical and laboratory examination is required with an eye towards ruling out vasculitic involvement of other organ systems and other causes of vasculitis such as infections or collagen vascular disease. Treatment • Withdrawal of all drugs • Antihistamine (H1 antagonists) • Soothing lotion for topical application • Corticosteroids – topical steroids may provide some relief. Systemic corticosteroids are indicated if signs and symptoms are severe • Adrenaline in case of anaphylaxis • Other measures like fluid and electrolyte balance maintenance, wet compresses, etc. ERYTHEMA MULTIFORME It is a self limited, usually mild but relapsing exanthematic reaction of skin probably triggered by circulating immune complexes, most often related to recurrent herpes simplex infection, Fig. 18.10: Toxic epidermal necrolysis—sheets of necrotic tender epidermis over the back
  • 185. Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome 177 characterized by skin lesions with varied morphology (typically target lesions) in acral areas, frequently associated with mucous membrane lesions. • Herpes virus infection is the single most important cause of erythema multiforme (EMF). • Other important agents include Mycoplasma pneumoniae, drugs and malignancies. • EMF is common in young adults. • Prodromal symptoms are minimal to absent. • The lesions seen are urticarial papules, target lesions, vesicles and bullae. • The lesions occur in a symmetric fashion on the extensor aspects of limbs, palms and soles. • The target lesions /iris lesions have three zones of color: The central dark cyanotic area, pale edematous zone and the surrounding erythema (Figs 18.6 and 18.7). • The iris lesions result from centrifugal spread of a red maculopapule as the center becomes cyanotic, purpuric or vesicular. Differential Diagnosis Urticaria, urticarial vasculitis, figurate erythemas (slow evolving lesions, usually asymptomatic, no mucosal involvement), acute febrile neutrophilic dermatosis, disseminated lesions of contact dermatitis, bullous pemphigoid, linear IgA dermatosis, herpes gestationis, lupus erythematosus, exanthematous or morbilliform drug eruption (accompanied by fever, pruritus, eosinophilia, involving trunk and extremities, sparing the face and pressure areas, fade with desquamation and postinflammatory hyper- pigmentation), viral exanthem (start on face and involve the trunk, maculopapular/ urticarial/ vesicular/petechial lesions associated with fever, conjunctivitis, and lymphadenopathy, fades without pigmentation and scaling), fixed drug eruption (solitary first, later new lesions appear with repeated attacks, common on limbs, hands and feet, genitalia and perianal area, also periorbital and perioral), Kawasaki’s disease (lips are red, dry with crust, transient red macules, conjunctivitis without exudates, strawberry tongue, lymphadenopathy), paraneoplastic pemphigus (severe necrosis of lips, eyes, oral mucosa, with polymorphous skin lesions, biopsy shows acantholysis and immunofluorescence confirms the diagnosis), Stevens Johnson syndrome (severe episodic acute mucocutaneous reaction, most often elicited by drugs and occasionally by infections, characterized by rapidly expanding irregular macules or atypical target lesions involving body surface area less than 10%, involvement of more than 2 mucosal sites), toxic epidermal necrolysis (mucosal erosions and epidermal detachment more than 30% of body surface area, skin tenderness, Nikolsky’s sign positive, histopathology shows full thickness epidermal necrosis with subepidermal cleft formation), acute graft versus host disease (also precipitating factor for Stevens Johnson syndrome, similar lesions, histopathology also can’t differentiate, lesions begin over the palms and soles first) and acute hemorrhagic edema of infancy (is a manifestation of leukocytoclastic vasculitis in infants and small children, it is characterized by symmetric erythematous and purpuric concentric rings in acral locations similar to target lesions that spontaneously resolve in about a week). • Treatment is symptomatic. If the herpetic lesions are clinically evident, acyclovir needs to be given. STEVENS-JOHNSON SYNDROME— TOXIC EPIDERMAL NECROLYSIS SPECTRUM Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are closely related severe acute mucocutaneous intolerance reactions most often elicited by drugs and less so by infections (Table 18.1).
  • 186. Essentials in Dermatology178 Table 18.1: Differentiating features between erythema multiforme and SJS-TEN Features Erythema multiforme SJS-TEN 1. Etiology HSV (in majority) Drugs (80-95%) 2. Course Acute, self limited, recurrent Acute, self limited, episodic 3. Prodrome Absent to moderate Intense, skin tenderness 4. Eruption Disseminated, symmetric, acral, face Disseminated, confluent, symmetric, on face, neck, trunk 5. Typical lesions Fixed plaques, target lesions, blisters, Macules, flat atypical target, central Nikolsky’s sign –ve necrosis, Nikolsky’s sign +ve 6. Mucosal involvement Frequent, mild oral Prominent, severe, 2-3 mucosal involvement 7. Body surface area <10% <10% to >30% 8. Constitutional symptoms Absent to moderate Prominent to severe 9. Pathology Satellite cell necrosis, DEJ blister formation, Massive keratinocyte necrosis, prominent mononuclear cell infiltrate, papillary sloughing of epidermis, dermal dermis edematous infiltrate slight to absent 10. Internal organs Not involved Not infrequent 11. Duration 1-3 weeks > 2-6 weeks 12. Complications None Septicemia, pneumonia, gastrointestinal hemorrhage, renal and cardiac failure 13. Mortality rate 0% 1-50% 14. Healing Without scarring Sequelae due to mucosal scars They have been classified based on the area involved as: • SJS— mucosal erosions and epidermal detachment below 10%. • SJS/TEN overlap— mucosal erosions and epidermal detachment between 10-30%. • TEN— mucosal erosions and epidermal detachment more than 30% . STEVENS-JOHNSON SYNDROME (SJS) • The important drugs causing SJS are phenytoin, phenobarbitone, sulfonamides, penicillins and NSAID’s. • It is common in children and young adults. • The disease is preceded by a nonspecific prodrome with fever, myalgia, rhinitis and cough. • Skin lesions occur abruptly and are purpuric macules, atypical target lesions and papules. • Bullous lesions may occur in oral, genital and anal mucosa. • Ulcerative stomatitis with hemorrhagic crusting is the most characteristic feature (Fig. 18.8). • Corneal erosions may lead to symblepharon, synechiae and opacities. • Constitutional symptoms may be severe during active stages. • Differential diagnosis: As given for erythema multiforme. • The treatment includes immediate withd- rawal of all potential causative agents, skin care, fluid and electrolyte balance, eye care, supportive care with antibiotics, diet and others. Patients have to be managed in an intensive care set up. Specific medications include steroids, intravenous immuno- globulins, plasmapheresis, hemodialysis, cyclophosphamide, and cyclosporine.
  • 187. Drug Eruptions, Erythema Multiforme, Stevens-Johnson Syndrome 179 TOXIC EPIDERMAL NECROLYSIS (LYELL’S SYNDROME) TEN is a rare life threatening mucocutaneous reaction characterized by widespread sheets of erythema, necrosis and bullous detachment of epidermis. • Incidence: 1 to 3 cases per million. • Pathogenesis: In predisposed patients, the drug metabolites may bind to epidermis and trigger an immune response leading to immunoallergic cutaneous adverse reaction. • Drugs causing TEN are antiepileptics (phenytoin, phenobarbital, carbamazepine), sulfonamides, ampicillin, allopurinol, antituberculous drugs (thiacetazone, isoniazid) and NSAID’s. Clinical Features • TEN begins with sheets of erythema covering wide areas. • In hours, the skin lesions become painful and extremely tender and small vesicles and bullae appear over the involved skin (Fig. 18.10). • The epidermis can be separated from dermis by slight tangential pressure (Nikolsky’s sign). • Mucosal erosions and conjunctival erosions are a constant feature. • Septicemia and bronchopneumonia are the important causes of death. Differential Diagnosis • As given for erythema multiforme. Staphylococcal scalded skin syndrome (SSSS) can be differentiated from TEN by occurrence in children, absence of mucosal lesions and absence of systemic features. Moreover in SSSS, the involved skin is dry and parchment- like while in TEN it is erythematous, purpuric and necrotic. Physical and chemical injury such as scalding and burns, solar erythema and chemical burns are other differential diagnosis, difficult in an unconscious patient. Treatment • Patients have to be managed in an intensive care set up with proper maintenance of fluid and electrolytes like Stevens Johnson syndrome. • Role of steroids is controversial. • Intravenous immunoglobulins have been found to be useful. • Plasmapheresis, hemodialysis, cyclophos- phamide, cyclosporine, N-acetylcysteine, thalidomide, etc are other treatment options.
  • 188. Essentials in Dermatology180 19 DISORDERS OF THE SEBACEOUS GLANDS Acne Vulgaris Acne vulgaris is a self-limited disease, seen frequently in adolescents, primarily involves the sebaceous follicles. Most cases of acne are pleomorphic, presenting with a variety of lesions- comedones, papules, pustules, nodules, and as sequelae to active lesions-pitted or hypertrophic scars. Pathogenesis Four major factors are involved in the pathogenesis: 1. Increased sebum production 2. Hypercornification of the pilosebaceous duct 3. Microbial flora 4. Inflammation. Increased Sebum Production Acnepatients,maleandfemale,excreteonaverage more sebum than normal subjects and the level of secretion correlates with the acne severity. Ductal Hypercornification Hypercornification of pilosebaceous ducts presents histologically as microcomedones and Disorders of Sebaceous, Eccrine andApocrine Glands clinically as blackheads and whiteheads. Thus comedones represent the retention of hyperproliferating ductal keratinocytes in the duct. Bacteria Acne is not infectious. However, three major organisms isolated – Propionibacteria (P. acnes, P. granulosum, P. avidum), Staphylococcus epidermidis and Malassezia furfur. Environment of bacteria (i.e. low pH, reduced oxygen tension and bacterial lipases, proteases, etc.) more important than absolute numbers. Inflammation Thedermalinflammationisnotcausedbybacteria in the dermis but from inflammatory mediators that diffuse from the follicle where they are produced by P. acnes. Natural History • Usually starts in adolescence and resolves by mid-twenties. • At least some degree of acne affects 95% and 83% of adolescent boys and girls. • Acnedevelopsearlierinfemalesthaninmales. • At the age of 40 years, acne may persist in 1% of males and 5% of females.
  • 189. Disorders of Sebaceous, Eccrine and Apocrine Glands 181 Clinical Features • Occurs predominantly on the face (99%), back (60%) and chest (15%). Infraorbital area spared even in severe acne. • Two types of lesions: i. Non-inflammatory (comedones) ii. Inflammatory • Comedones are the pathognomoniclesions of acne(Fig.19.1).Theyareconical,raisedlesions with a broad base and a plugged apex. Two types of comedones – blackheads/open comedones (black color due to oxidation of melanin) and whiteheads/closed comedones. • 25% of the whiteheads resolve within three dayswhileanother75%developintoinflamed lesions. • Inflammatory lesions include papules, pustules and nodules or nodulocystic lesions (Figs 19.2 and 19.3). • Nodules occur more frequently in males and may be interconnected with sinuses. • In its most severe variant, acne can present with cysts and abscesses. • Some amount of scarring in 90%. These could be hypertrophic scars, keloids, atrophic scars or ice-pick scars. • Acneseveritycanbegradedintomild(multiple open and closed comedones are present, with few inflammatory papules), moderate (with erythematous papules and pustules which are the predominant lesions, and disease is limited to the face), moderately severe (with erythematous papules, pustules, and nodules that are present on the face), and severe (with multiple painful nodules that are present on the back in spite of aggressive topical and oral interventions, respond only to isotretinoin). Differential Diagnosis Acne is rarely misdiagnosed. The commonest mistaken diagnosis is rosacea (has facial flushing, typically pustules occurring over erythematous background, localization of lesions to mid-face, Fig. 19.1: Acne vulgaris–face showing comedones, papules, and pustules Fig. 19.2: Acne vulgaris–face showing comedones, papules, pustules and nodules Fig. 19.3: Acne vulgaris–nodulocystic lesions in addition to other acne lesions over the cheek
  • 190. Essentials in Dermatology182 absence of seborrhea, comedones, nodules, cyst or scarring). Perioral eczema/dermatitis can be confused with acne in females, but lesions itch, the skin is dry and there are no comedones. Whiteheads may be confused with milia (which are predominantly infraorbital in distribution and are whiter). Acneiform drug eruptions are sudden onset, follicular monomorphous eruptions characterized by papules and pustules resembling acne, induced by skin exposure to various industrial chemicals or medications. Folliculitis due to Gram-negative organisms can complicate acne therapy and rarely folliculitis due to Candida may also present as multiple pustular eruptions as may S. epidermidis folliculitis. Demodex folliculitis can present as non- responsive acne, which best responds to metronidazole or topical permethrin. Rarely acne vulgaris need to be differentiated from Pityro- sporum folliculitis, acne agminata, adenoma sebaceum lesions of tuberous sclerosis, pseudofolliculitis barbae, plane warts, acneiform eruption of Behcet’s disease. Treatment Treatment involves counseling, acne assessment and appropriate and ethical prescribing based on the history, acne severity, lesion type and the psychological effects of the disease. The various modalities of treatment can be classified into topical and systemic therapies (Table 19.1). Topical • Predominantly comedolytic: – Tretinoin (0.025%, 0.05%, 0.1% creams, gels) (reduce number of existing comedones and prevent formation of new comedones by loosening ductal kerati- nocytes) - The best treatment for comedones. Almost every patient benefits from topical retinoids. – Adapalene (0.1% cream, gel, solution). – Azelaic acid (20% cream). • Predominantly antimicrobial: – Clindamycin (1% gel, solution). – Erythromycin (1.5-2% gel, solution, ointment). – Benzoyl peroxide (2.5-10% gel, lotion, cream). – Nadifloxacin. – Clarithromycin. – Tetracycline. – Sodium sulfacetamide- sulphur combi- nation. • Predominantly anti-inflammatory – Adapalene. – Topical antibiotics. – Combination preparations. – Zinc and erythromycin. – Benzoyl peroxide and erythromycin. Systemic • Oral antibiotics (oral tetracycline 250-500 mg 1-4 times a day, oral minocycline 50-100 mg daily, doxycycline 50-100 mg daily, erythromycin 250-500 mg 2-4 times a day, trimethoprim 300 mg twice a day, pulse dosing with azithromycin -250 mg daily for three days in a week for 4-6 months or roxithromycin). • Hormones (anti-androgens like 2 mg cyproteroneacetatewith35microgramethinyl estradiol, flutamide-250 mg twice a day, oral contraceptive pills, spironolactone 100-200 mgdaily,finasteride2.5-5mgdaily):Indicated for women with acne located primarily on the lower face and neck, those with PCOS and late onset acne, late onset adrenal hyperplasia or other identifiable endocrinologic con- ditions. • Isotretinoin: It is the only anti-acne agent that affects all four of the known major etiologic mechanisms: sebum production, comedo- genesis, Propionobacterium acnes (P. acnes) colonization of ductal and skin surface, and monocyte chemotaxis-induced inflammation. It is indicated for nodulocystic acne, acne
  • 191. Disorders of Sebaceous, Eccrine and Apocrine Glands 183 conglobata, acne fulminans, moderate acne relapse, significant psychosocial impairment, marked concomitant seborrhea, Gram- negative folliculitis, and scarring or persistent dyschromia. Acne therapy is usually initiated at a dose of 0.5 mg/kg daily for the first 2-4 weeks and then increased to 1.0 mg/kg/ day for the remainder of the 20 weeks course. The chance of a prolonged remission is greater whenatotaldoseof120to150mgperkilogram of body weight is achieved. • Corticosteroids (co-prescribed with isotretinoin in severe acne variants). Miscellaneous • Oral zinc. • Dapsone (nodulocystic acne). • Clofazimine (acne fulminans). • NSAIDs (to reduce inflammation). • Chemical peels. • Cryotherapy. • Blue light therapy. Surgical Procedures • Comedone extraction. • Aspiration of cysts. • Incision and drainage (large cysts). • Intralesional steroid (0.1 ml triamcinolone injectedintobaseofthecyst;reducesscarring). Acne Scar Surgery • Dermabrasion. • Laser abrasion. • Chemical peels. Course and Prognosis The course and prognosis of acne is highly variable. All acne causes scars. ACNE VARIANTS WITH MARKED INFLAMMATION Acne Conglobata It is a rare type of acne, which is highly inflammatory and presents with comedones, nodules, abscesses and draining sinus tracts. Healing occurs with severe scarring. It usually starts in adult life. Oral isotretinoin is the best treatment for patients in whom antibiotics are unsuccessful or in patients with very severe deep acne like this one. Follicular Occlusion Tetrad (Acne tetrad) It is a combination of acne conglobata, acne inversa/hidradenitis suppurativa, dissecting cellulitis of scalp and pilonidal sinus. It is more common in men. SAPHO Syndrome It is characterized bySynovitis, Acne (conglobata, fulminans), Pustulosis (pustular psoriasis, palmoplantar pustulosis), Hyperostosis and Osteitis. Acne Fulminans It is characterized by the sudden appearance of severe acne with systemic signs and symptoms (fever, leukocytosis, osteomyelitis, polyarthralgia, Table 19.1: Treatment guidelines for acne vulgaris Grade 1(Mild) Grade II-III(Moderate) Grade IV(Severe) Maintenance therapy Topical retinoids Topical retinoids Isotretinoin or Topical retinoids + BPO Benzoyl peroxide BPO or topical A/B Topical retinoids, (BPO) or topical oral A/B, hormone antibiotic (A/B) + therapy Oral A/B Hormone Rx
  • 192. Essentials in Dermatology184 polymyalgia). The disease exclusively occurs in teenage boys. The face is often not involved. Treated initially with high dose corticosteroids to control inflammation and then retinoids SPECIAL TYPES OF ACNE Acne from Drugs and Chemical Agents (Acneiform Eruptions) Due to topical or systemic glucocorticoids, anabolic steroids, INH, cyclosporine, iodides and bromides, lithium, etc. Oil Acne It is due to lubricating and cutting oil application andisseenmainlyonfrontofthighsandforearms, predominantly as comedones. Chloracne or Industrial Acne It is due to topical or systemic exposure to toxic chlorinated hydrocarbons and causes severe comedonal acne. Excoriated Acne It is seen in young women. Small acne spots are picked, squeezed and altered by manual interference. Resulting papules are crusted and inflamed. ROSACEA It is a centrofacial disease, which is characterized by papules and papulopustules against a vivid erythematous background with telangiectases, preceded by episodes of flushing (Fig. 19.4). Later, there may be diffuse hyperplasia of connective tissue with enlarged sebaceous glands, particularly of the nose (rhinophyma). Women are more often affected than men in their third and fourth decade. Ophthalmological complications are common, occurring in over 50% of the patients with rosacea. These include sensation of grittiness or irritability of the eyes, often accompanied by visible reddening of the conjunctiva. Blepharitis, keratitis, episcleritis, chalazion, and hordeolum are also common. Differential Diagnosis Important differential diagnoses include acne vulgaris (typical acne lacks the redness, telangiectasia, and flushing of rosacea), lupus erythematosus (DLE—scarring, scaling and follicular plugging are not features of rosacea, SLE-butterfly erythema is not pustular and is usually associated with systemic symptoms), perioral dermatitis (lesions itch, the skin is dry), seborrhoeic dermatitis (scaling in typical seborrhoeic areas) and demodex folliculitis (clearlymimicsrosacea).Nasalsarcoidosis (lupus pernio) is the differential diagnosis for rhinophyma. Treatment Papulopustular rosacea responds well to treatment. Topical treatment with metronidazole (1% cream, 0.75% gel, cream, lotion) is effective. Additional topical therapies reported as effective include tetracycline, clindamycin, erythromycin, azelaic acid 20% cream and 15% gel, 0.025% Fig. 19.4: Rosacea—face showing erythema topped by erythematous papules and pustules
  • 193. Disorders of Sebaceous, Eccrine and Apocrine Glands 185 retinoic acid and 10% sulphur cream. Topical imidazoles are also gaining popularity in the treatment of rosacea. Effective oral treatment includes tetracycline or oxytetracycline 250 mg twice daily and erythromycin 250 mg twice daily. More recently developed tetracyclines such as minocycline, lymecycline and doxycycline are often used. Oral metronidazole (750-1500 mg in divided doses) is also effective. Oral isotretinoin (10-60 mg/day) is an alternative in resistant rosacea and can even improve rhinophyma. Flushing and burning are the most difficult features of rosacea to treat. Non-cardioselective beta-blockers such as propranolol 40 mg twice daily or nadalol 40 mg daily, clonidine 50 mcg twice daily, and rilmenidine 1 mg daily. Advent of vascular laser and intense pulsed light sources has provided a range of highly effective treatments for ablation of telangiectasia. Surgical treatment is a very successful treatment in rhinophyma. Excellent cosmetic results can be obtained by scalpel or razor remodeling, electrocoagulation, cryosurgery, excision and vaporization with argon, carbon dioxide or Nd: Yag lasers. PERIORAL DERMATITIS It is facial dermatosis predominantly affecting females of childbearing years. The dermatosis is characterized by an erythematous, micropapular, fine scaling eruption classically affecting the nasolabial folds, chin, and upper lip, sparing a rimofskinatthevermilionborder.Innearlyevery patient, there is striking dependency on topical steroids. A frequently heard story is that the patient presents with the earliest signs of rash and is given a potent topical steroid. The condition then shows improvement but any attempt to stop the treatment dramatically worsens the condition after a few days. Differential Diagnosis The important differential diagnoses include rosacea (usually no telangiectasia or flushing in perioral dermatitis), lip licking cheilitis (seen predominantly in 7-15 years old age group, the rash is caused by repeated licking of skin around the mouth and is marked by a scaling, pink band around the mouth and involvement of lips), seborrhoeic dermatitis (not usually circumoral and the scalp, ears and eyebrows are commonly involved), contact allergic dermatitis (does not sparetheimmediateperioralarea),late-onsetacne vulgaris (evidence of comedones, large papules and cysts in wider distribution and responds moreslowlytotreatment),acneagminata(difficult to distinguish if confined to perioral area but can be differentiated histologically) and facial Afro- Caribbean childhood eruption (FACE) (do not spare the perilabial skin, pustules do not occur, occur often in males). Treatment The most important measure is usually to discontinue the application of the topical corticosteroids.Thepatientshouldbewarnedthat an initial flare may develop after the withdrawal of a topical corticosteroid. A four week course of oral tetracycline or its analogues such as minocycline, doxycycline or lymecycline is usually all that is required. Topical metronidzole, topical erythromycin, and topical tetracycline have also been used. DISORDERS OF ECCRINE SWEAT GLANDS Disorders of eccrine sweat glands may be broadly classified into four-chromhidrosis, hyperhidrosis, hypo- or anhidrosis and miliaria. Chromhidrosis It means secretion of colored sweat. It is an exceedingly rare functional disorder of the
  • 194. Essentials in Dermatology186 apocrine sweat glands. The colored sweat may be yellow (most common), blue, green, or black. Colored sweat fluoresces and is caused by lipofuscin. Topical capsaicin satisfactorily reduces facial and nipple chromhidrosis. Hyperhidrosis It means excessive sweating which could be localized or generalized. It may occur as consequence of a number of causes. Most commonly excessive sweating of the palms and soles occurs during mental stress, and may be associated with tachycardia and vasomotor instability. Palmoplantar Hyperhidrosis (Emotional Hyperhidrosis) This type of hyperhidrosis is usually localized to the palms, soles or/and axillae. Frequently there is a family history and commonly begins in childhood or around puberty. There is a tendency of spontaneous improvement after the age of 25 years. Sweating may be intermittent (triggered by anxiety, stress, or fear) or may be constant. Apart from the embarrassing nature of the disorder, complications include pompholyx, contact dermatitis, and pitted keratolysis. Gustatory Hyperhidrosis Sweating on the lips, forehead and nose after eating certain foods is known as gustatory sweating. Gustatory sweating may be idiopathic, post-peripheral nerve injury (parotid surgery, auriculotemporal nerve syndrome or von Frey syndrome, cervical sympathectomy), sensory neuropathy(diabetesmellitus,postherpeszoster). Treatment Topical anticholinergics (0.5% glycopyrronium bromide cream), formalin 1% soaks, glutar- aldehyde 10% in a buffered solution, 20% aluminium chloride have been used. Ionto- phoresis either using tap water or anticholinergic drugs like glycopyrronium bromide is a satisfactory method. Direct current is usually used, with each palm or sole being treated for 30 min with 20 mA initially three times a week. Botulinum toxin injection into 4 cm2 areas on the palms, soles or axillae dramatically reduces sweating. The hypohidrosis continues for an average of 7 months. Axillary hyperhidrosis may be effectively controlled by excision of the most active sweating portion of the axillary skin, alternatively liposuction removal may be used. Anhidrosis (Hypohidrosis) It can result from poral occlusion, congenital or acquired absence of sweat glands, damage to sweat gland function or dysfunction of sympathetic nerves in neuropathies. It may be localized or generalized. Miliaria Itresultsfromtheobstructionoffreeflowofeccrine sweattotheskinsurfaceandretentionofthesweat within the skin. It manifests with a variety of signs and symptoms. Miliaria crystallina (Sudamina) consists of non-inflammatory, superficial subcorneal translucent vesicles that easily rupture when rubbed with a finger. Miliaria rubra (prickly heat) causes pruritic inflammatory papules around the sweat pores, follows repeated episodesofsweatinginahothumidenvironment. Some of the eruptions of miliaria rubra become pustular resulting in miliaria pustulosa. Miliaria profunda results when sweat leaks into the dermis and presents as multiple discrete, flesh colored papules. The most common complications of miliaria are secondary infection and disturbance of heat regulation.Periporitis staphylogenes is the name given to multiple staphylococcal abscesses superimposed on miliaria rubra in young infants (Fig. 19.5). Postmiliarial hypohidrosis invariably occurs following miliaria and sweating may be depressed to half the normal amount for as long
  • 195. Disorders of Sebaceous, Eccrine and Apocrine Glands 187 as 3 weeks following miliaria. Affected persons may show decreasing efficiency, irritability, anorexia, drowsiness, vertigo and headache. Tropical anhidrotic asthenia is a rare form of miliaria with long lasting poral occlusion, which produces anhidrosis and heat retention. Treatment The most effective treatment is to place the patient in a cool environment as this will avoid further sweating. Avoidance of excessive clothing, friction with clothing, excessive use of soap and contact of the skin with irritants will reduce the incidence. Calamine lotion is effective in the relief of discomfort. Oral ascorbic acid 500 mg twice daily has been found to diminish the severity of miliaria. DISORDERS OF APOCRINE GLAND The capacity to produce an unpleasant odor is best-known property of apocrine gland. Physicians in the past relied heavily on detecting special body odors in diagnosis of diseases, e.g. fruity odour in diabetic coma, butcher shop odor in yellow fever, freshly baked bread odor in typhoid fever, etc. Fig. 19.5: Miliaria complicated by secondary infection of sweat glands—periporitis Bromidrosis (Bromhidrosis or Osmidrosis) Excessive odor arising from apocrine sweat, also known as fetid sweat or malodorous sweating. It is chiefly encountered in axillae. Often the patient complains of offensive axillary sweat but actually have no offensive odor. The complaint represents a phobia, delusion, paranoia or a lesion of the central nervous system. True bromidrosis is usually not recognized by the patient. Anti- bacterial soaps, deodoarants, frequent bathing, changing of underclothes, shaving of the axillae and application of aluminium chloride are all helpful measures. Fish Odor Syndrome (Trimethylaminuria) Affected individuals are unable to oxidize tertiary trimethylamine produced by oxidation of choline and carnitine in food. This results in formation of excessiveamountsofoffensivelysmelling(rotting fish) sweat. Defect in flavin containing monooxygenase 3 (FMO3) gene causes the disease. Diet low in carnitine and choline may help. Chromhidrosis Coloured apocrine sweat. Fox Fordyce Disease It is a disorder of the apocrine sweat gland comparable to prickly heat of the eccrine glands. It is a chronic itchy papular eruption of apocrine gland bearing areas-axillae (Fig. 19.6) and pubic area, classically seen in women between the ages of 15 and 35 years. Pruritus is often exacerbated by emotional or physical stimuli of the apocrine glands. Differential Diagnosis Includes lichen planus, lichen nitidus, infective folliculitis, chronic dermatitis, and syringoma.
  • 196. Essentials in Dermatology188 Treatment Estrogen therapy in the form of oral contraceptive pills is universally effective. Topical tretinoin, clindamycinsolution,UVphototherapyhavebeen tried. Treatment response with topical steroids or intralesional steroids is not satisfactory. Hidradenitis Suppurativa (Apocrinitis, Hidradenitis Axillaris, Acne Inversa) It is a chronic and cicatricial disease of apocrine gland bearing skin areas-axillae, anogenital skin (Fig. 19.7). The disease occurs in both sexes, usually in the second or third decade. It is rare before puberty. Affected patients are often overweight. Differential Diagnosis A solitary abscess in the early stage resembles a carbuncle, lymphadenitis, or an infected Fig. 19.6: Fox Fordyce disease–chronic itchy papular eruption in the axilla of a female epidermoid cyst. Other dermatoses that produce fistulas and sinuses should be excluded, such as scrofuloderma, actinomycosis, tularemia, and cat scratch disease. In the inguinal region, lymphogranuloma venerum, granuloma inguinale, Crohn’s disease, and ulcerative colitis should be excluded. Treatment Earliest lesions often heal quickly with intralesional steroid therapy. Concomitant use of antibiotics (minocycline, cephalosporins, ciprofloxacin) is recommended. Isotretinoin (1 mg/kg/day)iseffectiveinsomepatients.Insevere disease, removal of the affected area is often required. Wide local excision and healing by second intention is considered the surgical treatment of choice. Fig. 19.7: Hidradenitis suppurativa—nodules, sinuses and puckered scarring in the axilla
  • 197. Disorders of Hair and Nails 189 20 DISORDERS OF HAIR Alopecia Alopeciaislossofhair.Itmaybediffuseorpatchy, scarring or non-scarring. Diffuse Non-scarring Alopecia 1. Androgenetic alopecia: Terminal hair is converted into vellus hair. In men, recession of the frontal hairline near the temples and thinning over the vertex occurs (Fig. 20.1). In women, the scalp hair is generally diffuse but more so in the vertex area. Treatment includes in males- topical minoxidil (2 and 5% solution) or oral finasteride – competitive inhibitor of type II 5 α-reductase -1 mg/day and in females – topical minoxidil 2% and antiandrogens (spironolactone, cyproterone acetate, flutamide) and surgical treatment such as scalp reduction and hair transplantation. 2. Endocrine and nutrition related: Endocrine abnormalities of the thyroid, pituitary or adrenals can cause diffuse alopecia. Malnutrition and zinc deficiency or iron deficiency may also cause diffuse alopecia. 3. Telogen effluvium: Certain events can induce hair follicles to enter the telogen phase. This then Disorders of Hair and Nails induces a synchronous growth of hair follicles 6-10 weeks later such that more synchronous hair fallisseen.Itcommonlyfollowsdeliveryofababy, high fever, surgery or other stress. Drugs such as enalapril, beta blockers, retinoids, oral contraceptive pills, lithium, levodopa may be responsible. Treatment is reassurance, removal of stress or drug responsible. Hair density usually returns to normal in 6-12 months. Fig. 20.1: Androgenetic alopecia—scalp showing receding frontal hairline
  • 198. Essentials in Dermatology190 4. Anagen effluvium: Abrupt cessation of hair growth follows use of cytotoxic drugs (cyclophosphamide)(Fig.20.2),heparin,warfarin, colchicine, vitamin A, etc. Patchy non-scarring alopecia Alopecia Areata • Alopecia areata is an unpredictable usually patchy, non scarring hair loss condition. The word alopecia is derived from the Greek, “Alopex”, meaning “Fox mange” (baldness). Any hair bearing surface may be affected. • It is a common condition, probably auto- immune in etiology. Associated autoimmune diseases are Hashimoto’s disease, vitiligo and myasthenia gravis. • It affects men and women equally. • It generally starts in the 2nd or 3rd decade. Patients are frequently quite young, sixty percent of them present before 20 years of age. • The characteristic initial lesion is commonly a round or oval, totally bald, smooth patch involving the scalp (Figs 20.3 and 20.4) or any hair bearing area on the body. • A frequent feature in an alopecia areata patch is “Exclamation mark” hairs that are broken Fig. 20.2: Anagen effluvium – diffuse non-scarring alopecia following use of cytotoxic drugs Fig. 20.3: Alopecia areata – rounded bald smooth patches over the scalp Fig. 20.4: Alopecia areata – many bald patches coalescing over the scalp
  • 199. Disorders of Hair and Nails 191 short hairs tapering proximally. The pull test may be positive at the margins of the patch indicating very active disease. • Alopecia areata progresses as a wave of follicles, enter telogen prematurely. • The scalp is the most common site but any site can be involved. When the perimeter of the scalpisinvolved,itiscalled ophiasis(socalled from its resemblance to a snake) (Fig. 20.5), which is associated with poor prognosis. • Alopecia areata can occur as diffuse loss of hair from the scalp but spares the grey hair (Fig. 20.6). • If there are multiple patches on the scalp, they may become confluent to result in total loss of hair from the scalp, called as alopecia totalis (Fig. 20.7). Total loss of hairs from the whole body is called alopecia universalis. • Nail dystrophy is associated with alopecia areata in 10 to 66% of cases. Nail pitting “Hammered brass” (Fig. 20.8), trachyonychia (longitudinal striations), Beau’s line, onychorrhexis, thinning or thickening, onychomadesis, punctate or transverse Fig. 20.5: Alopecia areata—ophiasis pattern Fig. 20.6: Alopecia areata—diffuse hair loss sparing grey hair Fig. 20.7: Alopecia totalis Fig. 20.8: Alopecia areata – fine pitting of nail
  • 200. Essentials in Dermatology192 leukonychia, red spotted lunula and nail dystrophy may be seen in the nails. Classification of Alopecia Areata According to Pattern 1. Patchy alopecia areata-round or oval patches of hair loss (most common) (Fig. 20.3). 2. Reticulated pattern of patchy hair loss (Fig. 20.4). 3. Ophiasis, a band-like alopecia areata, hair loss occurs in the parietal temporo-occipital scalp (Fig. 20.5). 4. Ophiasis inversus(sisaipho), a rare band like pattern of hair loss in the frontal parieto temporal scalp (the exact opposite of ophiasis) 5. Diffuse alopecia areata, a diffuse decrease in hair density over the entire scalp. According to the Extent of Involvement 1. Alopecia areata, partial loss of scalp hair 2. Alopecia totalis, 100% loss of scalp hair (Fig. 20.7). 3. Alopecia universalis, 100% loss of hairs on the scalp and body. Indicators of a Poor Prognosis 1. Underlying atopy 2. The presence of other autoimmune diseases 3. Family history of alopecia areata 4. Young age at onset 5. Nail dystrophy 6. Extensive hair loss 7. Ophiasis. Diagnosis The characteristic non scarring patchy loss of hairs, the presence of exclamation point hair on the periphery, a hair pull test indicating telogen hair excess and in atypical cases skin biopsy showing specific findings (a peribulbar and at the lower one third of the follicle, a lymphocytic infiltrate, “swarm of bees”, with no scarring) all points towards the diagnosis. Differential Diagnosis Alopecia areata needs to be differentiated from tinea capitis, trichotillomania and secondary syphilis (moth-eaten appearance in beard or scalp). Treatment • Various modalities of treatment are available, the simplest of which are the use of counter irritants like phenol, benzoyl, tincture iodine, dithranol, etc. Physical modalities like UVB in erythema doses, grenz rays and thorium X-ray may be used with varied success. • Considering the autoimmune etiology of the disease various immunosuppressive drugs have been used. Among them, corticosteroids are important which can be used topically, intralesionally and systemically. • Photochemotherapy, contact immunotherapy (using dinitrochlorobenzene [DNCB], squaric acid dibutylester [SADBE], diphencyprone), topical minoxidil or topical cyclosporine may be used. Course and Prognosis Alopecia areata, however, a serious cosmetic problem, has unpredictable course. Tinea capitis: Discussed earlier under dermatophytosis. Trichotillomania • It is the term (Greek-“hair pulling madness”) first used by the French dermatologist Hallopeau to denote “a morbid impulse to pull one’s own hair”. • It manifests as one or a few small oval patches of hair loss which may occur in any hair area of the body in children or adults. • The patches are unusually irregular, asymmetric, and ill defined and have many broken hairs. • Common sites of involvement include scalp (Fig. 20.9), eyebrows, eyelashes, and pubic area.
  • 201. Disorders of Hair and Nails 193 • Trichophagy is rarely reported with trichotillomania, and when it occurs, trichobezoars (obstructive hair balls in the gastrointestinal tract) are the most severe complication. • Clinical differentiation from scalp alopecia areata is usually based upon the presence of short, broken hairs within the patch, and more irregular, often angular outlines of the area. Differentiation from tinea capitis may require Wood’s light examination, potassium hydroxide, or culture. The scalp in trichotillomania is usually healthy with broken hairs rather than scaly or erythematous in tinea capitis. • Any method of preventing grasping of hairs for a period of time (restraint, heavy gloves) will clarify the diagnosis and in one way serve as treatment, since hairs will grow normally in the area in the absence of trauma. One form of treatment consists of simply shaving the area. Psychological intervention and drugs such as clomipramine or fluoxetine may be given. Traumatic alopecia: It is due to traction or pressure. Secondary syphilis: Moth-eaten alopecia may be produced. Patchy/Diffuse Scarring Alopecia 1. Physical and chemical injury. 2. Infection – Kerion, favus, herpes zoster, folliculitis decalvans (Fig. 20.10). 3. Lichen planus and DLE. 4. Pseudopelade: Pseudopelade describes a scarring alopecia which represents the end stage of an idiopathic or unidentified destructive inflammatory process in the scalp. Characteristically, involves the vertex area of the scalp with crab like extensions (Fig. 20.11). 5. Malignancy – Basal cell carcinoma, squamous cell carcinoma. Excess hair Hirsutism: It refers to hair growth in a woman in areas of the body where hair growth is under androgen control and in which normally only post-pubescent males have terminal hair growth. These areas include the moustache, beard, chest and inner thigh. Causes are A. Ovarian (Polycystic ovarian disease, hyperthecosis), Fig. 20.9: Trichotillomania – unusually irregular patchy loss of hair over the temple area of scalp due to pulling of hairs Fig. 20.10: Perifolliculitis decalvans-scarring alopecia with folliculitis
  • 202. Essentials in Dermatology194 B. Drugs (androgens, oral contraceptive pills, glucocorticoids, diazoxide, minoxidil, phenytoin). C. Endocrine –Adrenal (Congenital adrenal hyperplasia, 21 and 11 hydroxylase deficiency, ACTH dependant Cushing’s syndrome). Others- hypothyroidism, acromegaly and D. Physiological – puberty, pregnancy. Treatment includes removal of precipitating cause/s, drug therapy with oral contraceptive pills, spironolactone, flutamide, finasteride, cyproterone acetate, and glucocorticoids, physical methods such as shaving, bleaching, waxing, laser, or electrolysis and topical therapy with eflornithine hydrochloride cream (slows hair growth by blocking ornithine decarboxylase). Hypertrichosis:Itspecificallyreferstohairdensity or length beyond the accepted limits of normal for a particular age, race, or sex. The excess hair may be generalized or localized and may consist of lanugo, vellus, or terminal hair. DISORDERS OF NAILS Nails may show their abnormalities—in shape, surface and color. Fig. 20.11: Scarring alopecia of scalp-crab like extensions over the scalp-pseudopelade A. Shape Abnormalities Anonychia: It means absence of nails. Usually a developmental anomaly. Clubbing: It means increased transverse and longitudinal curvature of nails with hypertrophy of the soft tissue components of the digit pulp (Fig. 20.12). To confirm it, one can oppose dorsal aspects of two fingers from opposite hands, between the two opposed nails normally a window of light is seen which get obliterated in clubbing(window closes). 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. Hodgkin’s) • GI malabsorption. Koilonychia: Reverse curvature in the longitudinal and transverse axis of nail gives a Fig. 20.12: Clubbing of nails
  • 203. Disorders of Hair and Nails 195 concave dorsal aspect to the nail, such nail is thought to have koilonychia (Fig. 20.13). Commonly, it is due to iron deficiency anemia. Macronychia and micronychia: Too large or too small nail in comparison with other nails of digits. Onycholysis: Distal or lateral separation of the nail from the nail bed (Fig. 20.14). May be seen in psoriasis, onychomycosis, etc. Fig. 20.13: Koilonychia—spoon like deformity of finger nails Fig. 20.14: Onycholysis with pitting of finger nails in psoriasis Fig. 20.15: Onychogryphosis – thickened great toe nail growing upwards Pterygium: When a central fibrotic tongue like band from proximal nail fold joins the nail bed dividing the nail proximally into two, it is known as pterygium. For example, it occurs in lichen planus. Subungual hyperkeratosis: It means excessive collection of squamous debris under the free edge of the nail. For example, it occurs in psoriasis, onychomycosis, etc. Onychogryphosis: Here nail gets thickened and grows upwards in a spiral manner attributed to chronic trauma (Fig. 20.15). Pachyonychia congenita: Here hypertrophy of nails is associated with nail bed and hyponychial hyperkeratosis (Figs 20.16 and 20.17). B. Surface Abnormalities Beau’s lines: They are transverse grooves on nails which arise out of temporary interference with nail formation (Fig. 20.18). Pitting: These are punctate erosions on the nail surface (Fig. 20.14). Commonly seen in psoriasis, and alopecia areata. Median canaliform dystrophy: Nail shows midlinesplitwithfirtreelikeappearanceofridges
  • 204. Essentials in Dermatology196 angledbackwards.Commonly,itaffectsthethumb nail and involvement is symmetrical. Onychoschizia: It is characterized by transverse splitting of nail into layers at or near the free edge of the fingers and toes. Onychauxis: Nail plate appears to be thickened due to subungual hyperkeratosis of nail bed seen in psoriasis, eczema, distal subungual hyperkeratosis. Onychoclasis: Breaking of the nail. Onychomadesis: Separation of the proximal part of nail plate from the matrix and bed with subsequent shedding of nail. Onychomalacia: Softening of nail. Onychorrhexis: Longitudinal ridging and fissuring of nail plate with brittleness and breakage. Onychotillomania:Compulsivepickingortearing of nail. Trachyonychia: Nails are rough and often thinned (20 nail dystrophy or sand paper nail) seen in alopecia areata, lichen planus, psoriasis, etc. C. Color Abnormalities Color changes in nail may be due to exogenous causes or endogenous causes. Leukonychia: This term is used for white discoloration of nails attributable to nail matrix dysfunction. Melanonychia: Means streaky hyperpigmen- tation of nails. Figs 20.16 and 20.17: Pachyonychia congenita—thickening of nails with subungual hyperkeratosis Fig. 20.18: Beau’s lines—transverse depressions equidistant from the nail folds Fig. 20.16 Fig. 20.17
  • 205. Disorders of Hair and Nails 197 Terry’s nail: Nail is white proximally but normal distally. It occurs in congestive cardiac failure, cirrhosis or adult onset diabetes mellitus. Red lunulae: Nail shows erythema of all or part of lunula. Mostly affects thumb nail. Dotted red lunula occurs in psoriasis. Other causes are congestive cardiac failure, cirrhosis of liver, systemic lupus erythematosus, etc. Splinter hemorrhages: They represent longitudinal hemorrhages in the nail bed, resemblingthepatternofsubungualvessels.They may occur in dermatoses like psoriasis, dermatitis, fungal infection or systemic diseases like endocarditis, systemic lupus erythematosus, mycosis fungoides, rheumatoid arthritis, etc. Half and half nails: It is onychopathological index of renal diseases and nail exhibits either normal or whitish proximal half and distinctly abnormal, brownish distal portion (Fig. 20.19). Fig. 20.19: Half and half nail – proximal half white and distal half brownish Infections of Nails and Nail Folds Acute paronychia: It presents with painful swelling of the nail fold. Most commonly caused by staphylococci. Chronic paronychia: It presents with chronic swelling of nail folds of one or more fingers, often middle and index fingers, and is associated with candida and/or pseudomonas infection. Herpeticparonychia(Herpeticwhitlow):Itisdue to primary inoculation of herpes simplex virus on to the finger and presents as single/grouped vesicles close to the nail. Tinea unguium: It is the fungal infection of nail complex by a dermatophyte and may be distal subungual infection, proximal subungual infection, or superficial white onychomycosis Onychomycosis: It includes tinea unguium and also infection by non-dermatophytic fungi including yeasts.
  • 206. Essentials in Dermatology198 21 PORPHYRIA • Porphyrias arehereditary disturbances in the synthesis of heme involving well-defined enzymatic defects. • The term “porphyria” is derived from the Greek word for “purple” and originally referred to the red to purple color of the urine of patients affected by acute intermittent porphyria. Other forms of porphyria produce urine that varies from pink to red to brown. Unlike findings with hematuria and pigmenturias (e.g., hemoglobinuria due to hemolysis, myoglobinuria caused by rhabdomyolysis), routine dipstick tests are negativeforthepresenceofhemeinporphyria patients. • Porphyrins also account for the fluorescence of urine viewed with a Wood’s lamp. • Almost all are inherited in an autosomal dominant pattern except congenital erythropoietic porphyria which is inherited in an autosomal recessive manner. • In addition, although the enzyme defects are genetic and permanent, the symptoms are often intermittent and do not appear until puberty except in congenital erythropoietic porphyria and hepatoerythropoietic porphyria (both manifest in infancy or Metabolic and Nutritional Disorders childhood, resemble clinically each other). This is true in porphyria cutanea tarda, acute intermittent porphyria, and variegate porphyria. • Photosensitivity in porphyria is due to absorption of UV radiation in soret band (400-410 nm). • Factors which precipitate are four m’s: medication (ethanol, oestrogens, iron, hexachlorobenzene), menses, malnutrition and medical illness. Clinical Classification • These disorders can be classified into those without vesicobullous lesions and those associated with them. • The former includes delta aminolevulinic acid dehydratase deficiency porphyria and acute intermittent porphyria (have no cutaneous manifestations), and erythropoietic proto- porphyria (can cause photosensitivity, but vesicobullous lesions are rare). • The latter includes congenital erythropoietic porphyria (Gunther’s disease), hepato- erythropoietic porphyria, hereditary coproporphyria, variegate porphyria (most prevalent in white population of South Africa) and porphyria cutanea tarda (PCT).
  • 207. Metabolic and Nutritional Disorders 199 Congenital Erythropoietic Porphyria • Congenitalerythropoieticporphyriamanifests in infancy or early childhood. • It is the result of defective activity of the enzyme uroporphyrinogen cosynthase. • Clinical manifestations include severe bullouscutaneousphotosensitivity(Fig.21.1), hypertrichosis (Figs 21.2 and 21.3), erythrodontia (fluorescent teeth), hemolytic anemia with splenomegaly, and bone abnormalities. However, the first clue to the diagnosis in infancy is generally not one of these striking cutaneous changes, but rather the pink or burgundy discoloration of urine (staining of diapers) due to massive porphyrinuria (Fig. 21.4). Diagnosis Markedly elevated levels of uroporphyrin I and coproporphyrin I in urine, stool and RBCs. Differential Diagnosis Other childhood photosensitivity disorders • Treatment of this disorder is aimed at the cutaneous photosensitivity or at the anemia and its complications. Sun protection (clothing better than sunscreens) and ingestionofbetacarotenemayamelioratesome portionofthephotodamage.Othermodalities,Fig. 21.1: Congenital erythropoietic porphyria– blistering over the fingers Figs 21.2 and 21.3: Congenital erythropoietic porphyria—a child having photosensitivity and hypertrichosis of face and trunk Fig. 21.2 Fig. 21.3
  • 208. Essentials in Dermatology200 chronic transfusion regimens and splen- ectomy, the risks must be weighed against the severity of the disorder in each individual case. Bone marrow transplantation successful in some cases. Porphyria Cutanea Tarda • PCT was first recognized by Waldenstrom in the 1930s, who identified a group of patients with excessive porphyrins in the urine, skin lesions in light exposed areas and a late (‘tarda’) onset in adulthood (in contrast with Gunther’s disease), so he called the disease ‘porphyria cutanea tarda’. • Most common type of porphyria due to deficiency of enzyme coproporphyrinogen decarboxylase. • Clinical signs include darkening of the urine (Fig. 21.5) and cutaneous photosensitivity manifested as fragility and bullae of sun exposed skin, scarring (Fig. 21.6), hyper- trichosis and pigmentary and sclerodermoid changes. In severe cases, the clinical appearance may be similar to that of congenital erythropoietic porphyria. Diagnosis Wood’slampexaminationofurineshowsorange- red fluorescence. Total porphyrins and uroporphyrins are raised in urine and plasma; coproporphyrins raised in stool; porphobilinogen Fig. 21.4: Congenital erythropoietic porphyria–pink to red discoloration of urine in the test tube Fig. 21.5: Porphyria cutanea tarda– darkening of the urine Fig. 21.6: Porphyria cutanea tarda–scarring and pigmentary changes following photosensitivity
  • 209. Metabolic and Nutritional Disorders 201 and delta aminolevulinic acid are normal in urine. Immunofluorescence of skin demonstrates IgG and other immunoglobulins at dermo-epidermal junction, and in and around blood vessels. Differential Diagnosis Some forms of epidermolysis bullosa acquisita look similar as does drug induced pseudo- porphyria (usually furosemide) in renal dialysis patients • Avoid hepatotoxic agents. Unlike other porphyrias, it is usually not inherited and responds to different treatments (venesection and antimalarials). If hepatitis C is documented, treat it with interferon and ribaverin PRIMARY CUTANEOUS AMYLOIDOSIS • Primary cutaneous amyloidosis is defined as cutaneous amyloidosis in the absence of other systemic or dermatological disease. • The various localized forms of primary cutaneous amyloidoses include the more common papular (lichen amyloidosis) and macular types and the rare nodular or tumefactiveform. • Single or multiple nodules involving the trunk or limbs characterize the nodular form. It is due to localized plasma cell dyscrasia. • Lichenamyloidosisisthemostcommonform characterized by numerous pruritic, brownish lichenoid papules distributed over the extensor surface of legs (Fig. 21.7) and forearms and upper back. • Macular amyloidosis typically manifests as brownish patches with a reticulate or rippled pattern, involving the upper back (Fig. 21.8), arms and lower extremities. • In some patients features of both lichen and macular amyloidosis can coexist and the term ‘biphasic amyloidosis’ has been coined for these. Extensive variants of both macular and papular amyloidosis have also been described. • On the other hand, amyloidosis cutis dyschromica (ACD) is a rare distinct type of primary cutaneous amyloidosis, which is characterized by reticulate hyperpig- mentation with hypopigmented spots seen almost all over the body without any papulation. Fig. 21.7: Lichen amyloidosis–pruritic brownish lichenoid papules affecting the extensor aspect of lower leg Fig. 21.8: Macular amyloidosis—rippled pigmentation over the upper back
  • 210. Essentials in Dermatology202 Differential Diagnosis For macular amyloidosis is postinflammatory hyperpigmentation, atopic dermatitis, lichen simplex chronicus and fixed drug eruption. Lichenamyloidosisneedstobedifferentiatedfrom lichen planus and lichen simplex chronicus. Nodular amyloidosis, clinically needs differentiation from naevus lipomatosus, lipoma, cysts,lymphomaandhistologicallyfromallforms of amorphous deposits, such as gout and nodular elastosis. • Treatment is symptomatic with topical corticosteroids (under occlusion), dimethyl sulfoxide (DMSO) and sometimes derma- brasion. XANTHOMATOSES Xanthomas are composed of masses of lipid containinghistiocytesformingpapular,nodular, and plaque like lesions in the skin, tendons and sometime in the internal organs. Xanthomas are important clinical finding as they often evolve in the presence of elevated blood lipids and lipoproteins. Lipoproteins are macromolecular complexes that carry hydrophobic plasma lipids, particularly cholesterol and triglycerides, in the plasma. An elevation of serum lipid levels is called hyperlipidemia, or hyperlipoproteinemia while the term dyslipoproteinemia signifies abnormalities in serum lipoproteins, whether or not serum lipid levels are categorically elevated or not. Of clinical interest is the fact that different species of lipoproteins typically produce different types of xanthomas. Thus, the type of xanthoma observed in a particular patient provides important clues as to the type of hyperlipo- proteinemia. Xanthelasma Palpebrarum • Soft, velvety papules and plaques arranged around eyelids. • Common sites – upper eyelid, inner canthus (Figs 21.9 and 21.10) • Signify a systemic hyperlipidemia – usually LDL elevations • Usually occur in normolipidemic individuals but may be seen in familial hypercholestero- lemia, dysbetalipoproteinemia, mixed hyperlipidemia. Secondary causes are obstructive liver disease, myxedema, and diabetes mellitus. • Treatment options includes surgical excision, electrofulguration, trichloroacetic acid chemical cautery , and CO2 laser. Tuberous Xanthomas • Firm, yellow-orange, often with an erythe- matous halo, small papules (0.5 cm in Fig. 21.9: Xanthelasma palpebrarum Fig. 21.10: Arcus juvenilis
  • 211. Metabolic and Nutritional Disorders 203 diameter)tolobulatedtumors(2.5cmormore) (Fig. 21.11). • Usually painless but may be tender on pressure. • Sites – knees, elbows, buttocks and pressure points, typically bilateral. • Seen with raised LDL levels – Familial hypercholesterolemia, dysbetalipopro- teinemia and secondary hyperlipidemias (hypothyroidism, chronic biliary disease) Tendinous Xanthomas • Slowly enlarging subcutaneous nodules attached to tendons, ligaments, fascia and periosteum (sub-periosteal) (Fig. 21.12). • Overlying skin appears normal. • Sites – extensor tendons of hands and feet, Achilles tendon, sub-periosteal bony prominences such as malleoli and elbows • Occur in severe hypercholesterolemia with raised LDL – Familial hypercholesterolemia, less frequently in secondary hypercholestero- lemia (cholestasis). Eruptive Exanthomas • Pinhead sized asymptomatic yellow papules with a reddish base, usually fleeting in nature and appear in crops. • Sites – buttocks, shoulders and extensor surfaces of extremities (Fig. 21.13). • Occasionally, these papules may coalesce and overlie a tuberous xanthoma – tuberoeruptive xanthomas. • Associated with pure or mixed hyper- triglyceridemia and a high concentration of VLDL or chylomicrons. Fig. 21.11: Tuberous xanthomas over the buttocks Fig. 21.12: Tendinous xanthoma near the left 5th toe laterally Fig. 21.13: Eruptive papular and tuberous xanthomas over the elbows and knees
  • 212. Essentials in Dermatology204 • May occur in secondary hyperlipidemia of diabetes mellitus. Plane Xanthomas • Yellow-orange macules or slightly palpable plaques. • May occur at any site. • Plane xanthomas over palmar creases – ‘xanthoma palmaris et striata’ – patho- gnomonicofTypeIIIdysbetalipoproteinemia. • Plane xanthomas may occur in secondary hyperlipidemias (biliary cirrhosis, cholestasis, gammopathy). Intertriginous Xanthomas • They appear as flat to slightly raised yellow dermal plaques with corrugated surface within or adjacent to finger webs (Fig. 21.14), axillae, buttocks and antecubital and popliteal fossa. • They are pathognomonic of type II hyper- cholestrolemia. Generalized Plane Xanthomas • These cover large areas of the face, neck and thorax and also may involve flexures and palms. • May be associated with myeloma, macro- globulinemia or lymphoma; rarely with normal plasma lipids. • 50% of patients may have hypolipidemia with low LDL levels. Table 21.1: Abnormalities of lipoprotein metabolism with their cutaneous features Lipid phenotype Lipoprotein phenotype Cutaneous features (Friedrickson) Isolated Hypercholesterolemia Familial hypercholesterolemia IIa Tuberous xanthomas, tendon xanthomas subperiosteal xanthomas Familial defective apo B100 IIa Tendon xanthomas Polygenic hypercholesterolemia IIa Usually none Isolated Hypertriglyceridemia Familial hypertriglyceridemia I, V None, occasionally eruptive xanthomas Familial lipoprotein lipase deficiency I, V Eruptive xanthomas, plaques Familial apo CII deficiency I, V Eruptive xanthomas, plaques Hypertriglyceridemia and Hypercholesterolemia Combined hyperlipidemia IIb Usually none; Dysbetalipoproteinemia III Tuberous xanthomas, tuberoeruptive xanthomas, xanthoma striata palmaris Fig. 21.14: Intertriginous xanthomas in the finger web spaces
  • 213. Metabolic and Nutritional Disorders 205 Cerebrotendinous Xanthomas • Rare autosomal recessive disorder with xanthomas in the tendons and the brain. • It is due to mutation in the sterol 27-hydroxylase (CYP27A) gene leading to defective conversion of cholesterol to bile acids with accumulation of cholestanol. • Severe neurologic disease and tendency to coronary artery disease. • Tendon xanthomas. • Urinary gas chromatography is the specific test for this disease. • Treated with oral deoxycholic acid to replace the bile acid pool. LIPOID PROTEINOSIS (URBACH – WIETHE DISEASE, HYALINOSIS CUTIS ET MUCOSAE) • Lipoid proteinosis is a rare disorder characterised by infiltration of hyaline materialintotheskin,oralcavityandinternal organs. • It is inherited as a monogenetic autosomal recessive disorder of normal chromosomal pattern and is due to mutations in the extra- cellular matrix protein 1 gene. • The earliest manifestation is hoarseness that develops in infancy, which can progress to complete aphonia without breathing difficulty. Examination of larynx frequently reveals infiltration, thickening and nodularity of cords. The mucosa of lip, pharynx and tongue (Fig. 21.15) may also develop firm yellow nodules giving it a cobblestone appearance. The tongue is enlarged and firm on palpation with decreased range of movements. Ankyloglossia can occur due to involvement of the lingual frenulum. Recurrent parotitis can occur. • In early stages, the skin lesions are crops of bullae, pustule, that leave behind acne like scars. Later on, patients develop hyper- keratotic wart like or nodular skin lesions over Fig. 21.15: Lipoid proteinosis – infiltrated lip and buccal mucosa dorsal aspect of hands, finger, elbows and knees, and patchy alopecia. • Depositionofhyalinematerialalongtheeyelid margins results in typical beaded papules – ‘moniliformblepharosis’.Thiseyelidbeading is the single most typical clinical feature of this disease (Fig. 21.16). In later stages, there may be total loss of eyelashes. Further infiltration of eyelids leads to its malfunction and can cause corneal ulcer. • Neurological abnormalities include calcifi- cation in the hippocampus and falx cerebri and temporal lobe epilepsy. Fig. 21.16: Lipoid proteinosis–beaded eyelid margins
  • 214. Essentials in Dermatology206 • Drusen of Bruch’s membrane seen in fundi in half the patients. • Sickle-shaped calcifications dorsal and lateral to sella turcica in skull X-ray films are pathognomonic. • The nature of hyaline material and underlying metabolic defect is unknown. It may represent an underlying lysosomal storage disorder with single or multiple enzyme defects, others have postulated it to be a disorder of collagen metabolism or collagen synthesis. • Distinctive histologic features include extreme dilation of blood vessels and thickening of their walls, progressive hyalinization of sweat glands, and infiltration of the dermis and subcutaneous tissue with extracelluar hyaline deposits and also demonstrable in walls of vessels. • Differentiation from erythropoietic protopor- phyria may be difficult histologically. Xanthomatoses and amyloidosis can be excluded histologically. In adults, differential diagnosis is from lichen myxoedematosus and myxedema with hoarseness have to be considered. • There is presently no effective therapy for lipoid proteinosis. Hoarseness may be relieved temporarily by surgical removal of vocal cord infiltrates. Facial lesions may be treated by dermabrasion, chemical skin peelingandblepharoplasty.Treatmentbyoral dimethyl sulphoxide has been claimed to be successful. PHRYNODERMA • Phrynoderma is a type of follicular hyper- keratosis typically seen in vitamin A deficiency. • This eruption has also been associated with deficiencies of vitamin B complex, C, and E, calories, and essential fatty acids. • The morphology of these lesions is variable and may range from filiform papules to small conical papules to large papules with large horny centers. They may be of the same color as the surrounding skin or may be slightly hyperpigmented. Elbows (Fig. 21.17), knees, anterolateral thighs, posterolateral superior forearms, extensor aspect of limbs, shoulders, abdomen, back and buttocks are the sites of involvement. • Differential diagnosis includes keratosis pilaris and Darier’s disease. • The treatment is oral vitamin A 100,000 IU/ dayfor2-3daysfollowedbytherecommended dietary requirements. PELLAGRA • Pellagra is a nutritional disorder that occurs due to deficiency of niacin or tryptophan or both. Therapy with isoniazid, 5-fluorouracil, 6-mercaptopurinemayprovokepellagra.Rare causes are carcinoid tumors, and Hartnup disease. • The term pellagra is derived from the Italian words ‘pelle agra’ meaning rough skin. • It is still endemic in areas of Africa and Asia due to poor nutrition and intake of certain cereals such as maize and jowar (Indian millet) as staple diet. Fig. 21.17: Phrynoderma hyper keratotic follicular papules over the extensor aspect of the forearm
  • 215. Metabolic and Nutritional Disorders 207 • In the present day context, in western world, pellagra is confined to individuals who have improper food intake such as psychiatry patients, alcoholics and recluses. • Pellagra is a clinical syndrome characterised by (1) symmetrical photosensitive skin eruption (2) gastrointestinal manifestations (3) neurological and psychiatric disturbances. These well-known group of symptoms are traditionally remembered as pellagra’s four D’s -dermatitis - diarrhea - dementia and when untreated, death - is very seldom seen. But most of the manifestations are borderline and/ or less typical in nature. • The initial manifestation is an erythematous, photosensitive pruritic rash that occurs on the dorsa of hands. • The usual sites affected are the face, neck and dorsal surfaces of hands, arms and feet. • The dorsa of the hands are the most frequent site from where it may extend up to arm to form the ‘glove’ or ‘gauntlet’ of pellagra (Figs 21.18 and 21.19). The dermatosis is strikingly symmetrical and clearly demarcated from the normal skin. • The feet is commonly involved and it may also affect the front and back of the leg to form a boot (Fig. 21.20). • In the face, an erythematous rash extending from the nose to the cheeks, chins, lips, may resemble lupus erythematosus “Butterfly rash”. Rarely eyelids and ears may be affected. Facial rash usually occurs concurrently with lesions elsewhere. • This eruption forms a broadband or collar around the neck, known as Casal’s ‘necklace’ (Fig. 21.19). In many instances, the necklace has an anterior continuation, also known as `cravat’. • Differential diagnosis includes drug eruption, photodermatitis, lupus erythematosus, and actinic reticuloid. • Classical pellagra responds dramatically to oraladministrationofnicotinamideorniacin (nicotinic acid) 100-300 mg/day in three divided doses. The mental changes disappear within 24-48 hours but skin lesions may take 3-4 weeks to disappear. Figs 21.18 and 21.19: Pellagra–chest and upper limb shows Casal’s necklace, and glove of hyper- pigmented flaking dermatosis Fig. 21.18 Fig. 21.19
  • 216. Essentials in Dermatology208 • It manifests insidiously between the ages of three weeks and 18 months (often when the baby is switched from breast milk to cow’s milk)withperiorificial(mouth,nose,eyes,ears, and perineum) (Figs 21.23 to 21.25) and acral (extensor surfaces of the major joints, fingers, and toes) dermatitis, alopecia and diarrhea (Mnemonic DAD to remember its clinical features). Fig. 21.20: Pellagra—”boot” of pellagrus dermatosis affecting lower legs ARIBOFLAVINOSIS (ORO-OCULO-GENITAL SYNDROME) • This syndrome occurs due to vitamin B2 (Riboflavin) deficiency and is characterized by mucocutaneous lesions of angular stomatitis, cheilosis, glossitis, seborrhoeic dermatitis (especially around the nose) (Fig. 21.21), scrotal (Fig. 21.22) and vulvar dermatitis, and increased corneal vascularity. • It usually responds promptly and dramatically to riboflavin supplementation with 5 to 15 mg of riboflavin daily for 2 weeks and correction of dietary errors. ACRODERMATITIS ENTEROPATHICA • Acrodermatitis enteropathica, an autosomal recessive disorder which appears to be due to defective absorption of zinc from the gastrointestinal tract. • It may be a presenting sign in cystic fibrosis or AIDS. Fig. 21.22: Ariboflavinosis–scrotal dermatitis Fig. 21.21: Ariboflavinosis–erythema and scaling of nasolabial folds
  • 217. Metabolic and Nutritional Disorders 209 Figs 21.24 and 21.25: Acrodermatitis enteropathica—perianal psoriasiform dermatosis • The primary cutaneous eruption is vesicobullous, which is symmetrical and grouped. The lesions soon evolve into erosive vesicobullous eruption or psoriasiform patches. Secondary infection of skin lesions with Staphylococcus aureus is common and impairs wound healing. • At the same time or shortly afterward, diffuse loss of hair and gastrointestinal disturbances manifest chiefly by diarrhea, occur. • Mental depression, listlessness, loss of appetite, perleche, photophobia, and blepharitis may occur during exacerbations. • Differential diagnosis includes atopic dermatitis, seborrheic dermatitis and psoriasis. • Laboratory verification of deficient plasma or serum zinc levels may be undertaken where facilities exist, otherwise, all these cases respond to zinc sulphate / gluconate (1 to 2 mg/kg body weight/day) given once Fig. 21.23: Acrodermatitis enteropathica– perioral dermatitis Fig. 21.24 Fig. 21.25 or twice daily. Skin lesions heal within one to two weeks. Diarrhea ceases and variability with depression of mood improves within 24 hours.
  • 218. Essentials in Dermatology210 22 GENETICS IN DERMATOLOGY Human genetics is the study of the range of biological variations in human beings with each individual showing considerable variability in his/her expression of disease. Human genome, the genetic material is packaged into units called chromosomes (Chromo-colored, somes-bodies). Each somatic cell contains 46 including 2 sex chromosomes. The karyotype of an individual identifies the number and structure of chromosomes. This is usually derived from peripheral blood cells (Tlymphocytes)thatarestimulatedtodivide.They are classified by the position of the centromeres and the proportion of long and short arms. Phenotype is the bodily manifestation of genotype. Genodermatoses are genetically determined skin disorders, course of events altered little by environmental agents with single gene disorders. Familial means a condition more common in relatives of an affected individual than in general population. Inheritedmeans that disorder is transmitted from one generation to next. Genetics and Genodermatoses Congenital is one that is present at/before birth, not necessarily genetically determined. Genetic Principles Gene is the sequence of bases on DNA that code for one polypeptide. Locus is the precise position of the gene on chromosome. Alleles are genes at a single locus, which may be heterozygous or homozygous. Dominantmeans full effect in heterozygous state. Expression means effects of a gene are variable. Penetrance is the frequency with which a gene produces an effect. If trait is non-penetrant, expressivity is zero. Genetic heterogeneity means similar/identical phenotypic features associated with genes at different loci, e.g. albinism, ichthyosis, cutis laxa, etc. Phenocopy means environmental causes mimicking genetic diseases. Pleiotropy meansmultiplephenotypiceffectsdue to primary action of an abnormal genotype, e.g. pachyonychia congenita, neurofibromatosis.
  • 219. Genetics and Genodermatoses 211 Mutation occurs due to point substitution or deletion and may be somatic or gamete mutation. Mosaicism relates to an individual with 2 or more cell lines of different genotypes derived from a single zygote. Autosomal Dominant Inheritance In this mode of inheritance, the gene locus is on an autosome and the trait is transmitted from generation to generation. • Both males and females are affected in equal proportions • Affected individuals are heterozygous • Everyaffectedpersonwillhaveaffectedparent • 50% of the children will be affected • Severity varies considerably in the family • Few show lack of penetrance. Examples: Ichthyosis, tuberous sclerosis, neurofibromatosis. Autosomal Recessive Inheritance In these pedigrees, the trait does not appear in successive generations. Parents appear entirely normal. • Bothmalesandfemalesareaffectedwithequal frequency • Affected individuals are homozygous (means one copy received from each parent “double dose of the gene”) • One fourth or 25% of children are affected • No family history may be there • High frequency of consanguinity can be expected • Disorders are very severe. Examples: Xeroderma pigmentosum, phenyl- ketonuria, etc. X-linked Recessive Inheritance In these conditions, the trait does not appear in successive generations. • Males are uniquely affected, whereas female siblings are carriers of the trait. Affected males are in different generations • Females are healthy carriers, pass on disease to ½ of their sons and ½ of their daughters are carriers • All of the daughters of an affected male are obligate carriers of the trait • Mother’s brothers are affected • Family history always not positive. Examples: Fabry’s disease, Menkes-Kinky’s disease. X-linked Dominant Inheritance Successive generations show the trait. • Females are predominantly affected • There is family history of recurrent losses of pregnancy early on. Although the losses may not be identified, it is often the case that the male fetus is preferentially aborted. • Hemizygous are males and heterozygous females. In most X-linked dominant traits the hemizygous male is more severely affected than the heterozygous affected female • Affected males transmit disorder to all his daughters, but none of his sons • Affected females transmit disease to ½ of their sons and ½ of their daughters. Example: Incontinentia pigmenti. Multifactorial Traits In single gene traits, transmission follows Mendel’s classical laws. In multifactorial inheritance, often referred to as polygenic inheritance, a definite familial tendency for development of the trait exists but the proportion of affected relatives is much less than expected for a single gene trait. Multiple genes modified by environmental factors influence the expression of the characteristic. Genetic Counseling Genetic counseling is the process undertaken to help patients to better understand the genetic basis of a medical problem and to plan for the future. By this definition, genetic counseling
  • 220. Essentials in Dermatology212 includes helping the patients to comprehend the medical facts, including the diagnosis, the probable course of the disorder and available management, the hereditary basis of the disorder, and the risk of recurrence in specific relatives. The counselingalsoincludesadiscussionofthecourse of action that seems appropriate in view of the risk and the family goals. Symbols in Common use in Preparation of a Family Pedigree Neurofibromatosis Type 1 (NF-1) • Neurofibromatosis type1 (NF-1), also known as von Recklinghausen’s disease, classic neurofibromatosis, or peripheral neuro- fibromatosis is the most common form of neurofibromatosis. • The NF1 gene responsible codes for “neurofibromin” on chromosome 17. • The clinical expression of NF-1 is highly variable. Roughly, half of NF-1 cases arise via spontaneous mutation and are not associated with any family history. • NF-1 is a multisystem disorder characterized by cafe-au-lait macules (CALMs), neuro- fibromas, Lisch nodules, optic gliomas, bony dysplasia, intertriginous freckling and autosomal dominant inheritance. • Neurofibromatosis is named after neurofibroma tumors. There are three types of neurofibromas: cutaneous, subcutaneous and plexiform. A single plexiform neurofibroma or two of any type are considered diagnostic of NF-1. Cutaneous neurofibromas (mollusca fibrosa) are soft lilac –pink tumors, sessile and dome shaped, sometimes pedunculated, most numerous on the trunk and limbs, hundreds may be present, ranging from a few millimeters to several centimeters in diameter. They can be easily pushed into underlying dermal defect with light digital pressure - “button holing”. When pressed, the soft tumors tend to invaginate through a small opening in the subcutaneous tissue, giving the feeling of a seedless raisin or a scrotum without a testicle (Fig. 22.1). The subcutaneous type may feel hard like a pencil eraser. They often cause localised pain or tenderness. On the other hand, plexiform neurofibromas are congenital and are pathognomonic for NF-1 (Figs 22.2 and 22.3). They feel like a “bag of worms” because of the many interdigitating PHAKOMATOSES (NEUROCUTANEOUS SYNDROMES) Phakomatoses or neurocutaneous syndromes are a rare group of disorders including neuro- fibromatosis, tuberous sclerosis, von Hippel- Lindau syndrome, and Sturge-Weber syndrome.
  • 221. Genetics and Genodermatoses 213 elementsandcanbethoughtofascombination of cutaneous and subcutaneous types. They present as a diffuse elongated fibroma along the course of the nerve, frequently involving the trigeminal or upper cervical nerves. Neurofibromas of the female areola and nipple are virtually pathognomonic for NF-1. • Cafe-au-lait macules (CALMs), another manifestation of NF-1, are discrete, well circumscribed, round or oval, uniformly pigmented patches (may be seen in normal population, segmental neurofibromatosis, familialCALMs,tuberoussclerosis,McCune Albright syndrome, ataxia telangiectasia, Bloom’s syndrome, Watson’s syndrome, Rubinstein-Taybi syndrome) (Figs 22.4 and 22.5). Solitary CALMs are a common finding, affecting up to one third of normal children. Multiple CALMs are rare, particularly in the white population. A diagnosis of multiple organ disorder, the most common being NF-1, should be considered in this instance. The minimal number of 6 lesions of CALMs was established as a criterion for the diagnosis of NF-1 (more than 1.5 cm in diameter in adults). They are the first feature of the disease to appear in all children. • Freckling is a useful and often overlooked sign of NF-1. Freckling involving areas of hyperpigmentation up to 2 or 3 mm in diameter occurs frequently in the axilla as well as other intertriginous regions. Basically, there are two kinds of neurofibromatosis freckles—those that are basically very small CALMs ordinarily present at birth or in the Fig. 22.2: Neurofibromatosis type 1 – plexiform neurofibromas affecting both lower limbs Fig. 22.3: Neurofibromatosis type 1—plexiform neurofibroma affecting foot Fig. 22.1: Neurofibromatosis type 1 – multiple neurofibromas over the trunk
  • 222. Essentials in Dermatology214 first year of life and distributed over the entire body and those that develop later in intertriginous regions (Crowe’s sign) (Fig. 22.6). Multiple melanotic macules of palms withvaryingsizefrom2to4mmmaybenoted in 90% of Indian cases (Fig. 22.7). This sign has been named as ‘Patrick Yesudian sign’ by various medical schools, in south India. • Lisch nodulesarepigmentedirishamartomas which appear as dome shaped lesions on the surface of iris. They are one of the most common manifestations of NF-1 and have significant diagnostic value. Fig. 22.7: Neurofibromatosis type 1—palmar freckling “Patrick Yesudian sign” Fig. 22.4: Neurofibromatosis type 1 – circumscribed pigmented patch of café-au-lait macule over the trunk Fig. 22.5: Neurofibromatosis type 1 – back showing neurofibromas and café-au-lait macules Fig. 22.6: Neurofibromatosis type 1—axillary freckling • Systemic features include: 1. Skeletal manifestations include bony dysplasias especially tibia, pseudo- arthrosis, cysts and scoliosis of thoracic region. 2. CNSmanifestations—Approximately50% of children with NF-1 exhibit a learning
  • 223. Genetics and Genodermatoses 215 disability, as well as attention deficit disorder.Moreseveredevelopmentaldelay, including mental retardation occurs in about 5%. Other features of NF-1 include macrocephaly, short stature, and hypertension (due to renal artery stenosis orrarelypheochromocytoma). 3. Endocrine disturbances of many types may be associated. • Diagnosis: The spectrum of clinical findings inNF-1isbroad,butonlysixfeaturesconstitute the seven established diagnostic criteria. These criteria were described at a National Institutes of Health (NIH)—sponsored consensus conference in 1987. These were updated in 1990. In the absence of a single “test” that can confirm the diagnosis, physicians often rely on these criteria. Two criteria are required for a definitive diagnosis and one is required for a presumptive diagnosis. 1. Six or more cafe-au-lait macules (CALM’s) measuring5mmormorebeforepubertyor 15 mm or more after puberty; 2. Axillary or inguinal freckling (Crowe’s sign), 3. Twoormoreneurofibromasoraplexiform neurofibroma; 4. Two or more Lisch nodules; 5. Optic nerve glioma; 6. Characteristic skeletal dysplasias (tibial or orbital dysplasia) and 7. Affected first degree relative. • Three of these criteria manifest themselves on to the skin (A single plexiform neurofibroma or two of any type, minimal number of 6 lesions of CALMs, and axillary freckling- Crowe’ssign).Itisoftenthedermatologistwho suggestsorconfirmsthediagnosisbasedupon cutaneous manifestations. • Management consists of genetic counseling, anticipatory guidance, and surveillance for complications. Tests such as MRI or X-rays should be done for clinical indications only. Children should be monitored for learning disabilities and provided cognitive and educational assessments as needed. Physical examinations should include measurement of height,weight,headcircumference,andblood pressure. Ophthalmologic check up is a must in all cases. Surgery is indicated in only select cases. • Risk of malignancy: NF-1 is also associated with increased risk of malignancy (malignant peripheral nerve sheath tumors in second or third decades). • Prognosis:Variable, dependent upon severity of involvement and development of malignancy. Cosmetic disfigurement is progressive and worsens with time. Mild course during childhood is not a guarantee for mild disease in adulthood. Tuberous Sclerosis (Bourneville’s Disease) • It is now frequently designated the tuberous sclerosis complex (TSC). It is an autosomal dominant human genetic disease charac- terized by widespread hamartomas, usually, occurring in the brain, eyes, skin, kidneys, liver, heart, and lungs. • This disorder derives its name from a description of its cerebral lesions by Bourneville in 1880. Its systemic nature was described by Vogt in the clinical triad (Epi- loi-a) of epilepsy (seizures),low intelligence (mental retardation) and facial lesions termed adenoma sebaceum (a misnomer for angiofibromas). Recent studies have shown that full triad was evident in only about one third of patients. • Two third cases are sporadic and one third are autosomal dominant. • Two genetic loci have been identified TSC1 (Hamartin) and TSC2 (Tuberin) on chromosome 9 and 16 respectively. These are
  • 224. Essentials in Dermatology216 tumor suppressor genes, which when deficient result in Mtor disinhibition and abnormal proliferation of tissues resulting in hamartomas. • Cutaneous features are the most frequent finding in TSC and if overlooked, will lead to a delay in diagnosis. Although, there is considerable variation in the age of expression of all the skin lesions, there is a trend towards the earlier expression of hypomelanotic macules and forehead plaques compared with facial angiofibromas and ungulal fibromas. Shagreen patches are usually present by puberty. • The relatively vascular and fibrous components of adenoma sebaceum (angiofibromas) determines their clinical appearance (Fig. 22.8). They range from white or flesh colored to classical red pink papules, 1-10 mm in diameter, symmetrically distributed over the nasolabial folds, cheeks and chin, sparing the upper lips. They are regarded by many as a primary pathogno- monic feature of TSC. • Shagreen patches are not as diagnostically useful as facial angiofibromas. They most often appear as flat, slightly elevated areas of the skin, soft and skin colored plaques of variable size (1 to 10 cm) with a “pig skin”, “elephant skin” or “orange peel appearance”. Usually, these lesions are localized asymmetrically over the dorsal body surfaces, particularly over the lumbosacral area (Fig. 22.9). • Periungual fibromas (Koenen’s tumors) common in adult patients with TSC, are much less frequent in children. They usually appear around puberty as smooth, firm, flesh colored excrescences and are usually 5-10 mm in length. They are located around or under the nail plate and arise from the bed under the nail plate or from skin of nail groove (Fig. 22.10). Regarded as angiofibromas, they are Fig. 22.8: Tuberous sclerosis – angiofibromas and forehead plaque seen over the face Fig. 22.9: Tuberous sclerosis – “orange peel appearance” of a circumscribed area in the lumbosacral area – Shagreen patch classified as primary or pathognomonic feature of TSC. • Ash leaf macules/spots (hypomelanotic macules) are the most frequent lesions in TSC patients. Since, they resemble the leaf of European mountain ash tree, they are called as ash leaf spots. They are ovoid or leaf shaped whitemaculesvaryinginsizefrom1-3cm(Fig.
  • 225. Genetics and Genodermatoses 217 22.8) and may be the only skin lesions in infants and if associated with infantile spasms,stronglysuggestthediagnosisofTSC. These ash leaf spots are predominantly distributedonthetrunkandbuttocksorlimbs. • Forehead fibrous plaque is classified histologically as an angiofibroma, although clinically it differs from the typical papulonodular angiofibroma because of fibromatous appearance (Fig. 22.5). It is one of the secondary features of tuberous sclerosis. • Molluscum fibrosum pendulum (skin tags) are commonly seen in normal elderly people and are uncommon in adolescents and young adults, and should alert to the possibility of TSC. In individuals with TSC, molluscum fibrosum pendulum is commonly seen on the neck, groin, axillae and near flexures of limbs, especially in adults. • Café-au-lait macules are not regarded as characteristic for TSC and are not included in the diagnostic criteria (Fig. 22.8). • Systemic features include: 1. Neurological findings: Tuberosclerotic nodules of glial proliferation occur in cerebral cortex, basal ganglia, and ventricle wall (60-70%) and are causes of mental retardation. Once calcified, these lesions are visible on skull radiographs as brain stones. Epilepsy is common, usually begins in infancy as infantile spasms or salam attacks. Autism, attention deficit disorder are other features. 2. Ocular: Retinal phakomas (lump of mulberry appearance) represent proli- feration of astrocytes. Hypopigmented spots in iris may be seen. 3. Cardiac: Rhabdomyomas may be present at birth and regress spontaneously in first few years. 4. Renal: Polycystic kidney disease, isolated renal cyst, angiomyolipomas, renal cell carcinoma. 5. Pulmonary: Multifocal micronodular pneumocyte hyperplasia, pulmonary cyst, lymphangiomyomatosis. 6. Gastrointestinal: Hamartoma and polyposis of stomach, intestine and colon. • Investigations include: – X-ray (skull, hands and feet, lungs); – CT scan brain; – MRI (brain parenchymatous lesions); – EEG (seizures); – Renal ultrasonogram; – ECHO heart (rhabdomyomas); – Neurodevelopmental testing; – Opthalmological examination. Diagnositic Criteria (Tuberous Sclerosis Alliance, Consensus Conference 1998) Major features 1. Facial angiofibromas or forehead plaque 2. Non-traumatic ungual or periungual fibroma 3. Hypomelanotic macules (more than three) 4. Shagreen patch (connective tissue nevus) 5. Multiple retinal nodular hamartomas 6. Cortical tuber 7. Subependymal nodule 8. Subependymal giant cell astrocytoma, 9. Cardiac rhabdomyoma, single or multiple 10. Lymphangiomyomatosis 11. Renal angiomyolipoma. Fig. 22.10: Tuberous sclerosis – periungual fibromas, also known as Koenen’s tumors
  • 226. Essentials in Dermatology218 Minor features: 1. Multiple randomly distributed pits in dental enamel 2. Hamartomatous rectal polyps 3. Bone cysts 4. Cerebral white matter migration lines 5. Gingival fibromas 6. Non-renal hamartoma 7. Retinal achromic patch 8. “Confetti” skin lesions 9. Multiple renal cysts. Definite TSC: Either 2 major features, or 1 major feature with 2 minor features. ProbableTSC:1majorfeatureand1minorfeature. Possible TSC: Either 1 major feature, or 2 or more minor features. • Treatment: 1. Facial angiofibromas: Dermabrasion, electrodessication, CO2, argon or pulsed dye laser 2. Seizures: For infantile spasms: ACTH/ steroids are useful. Seizures in children: vigabatrin is the drug of choice. • Prognosis is related to the extent of systemic involvement. Cardiovascular complications occur in 1st decade, brain tumor in 2nd decade, renal and pulmonary lymphangio- matosis in 4th decade are cause of morbidity and mortality. Von Hippel-Lindau Disease (VHL) • VHL also referred to as CNS angiomatosis is inherited in an autosomal dominant fashion with incomplete penetrance with VHL gene located on chromosome 3p25. Both sexes are equally affected. Hippel first described retinal angiomatosis in 1904. Lindau subsequently recognized association with central nervous system tumors and hence the eponym von Hippel Lindau disease was coined. • Cutaneous findings are portwine stains and café-au-lait macules. Dermal capillary malformation has predilection for the head and neck. Other manifestations are vascular malformations in the cerebellum and brain stem. Retina is also commonly affected. There may be cystic neoplasms or angiomatous lesions in the kidneys, liver and pancreas. Sturge-Weber Syndrome (Encephalofacial angiomatosis) • Sturge -Weber syndrome (SWS) is defined as facial portwine stain in association with ipsilateral plial (i.e. leptomeningeal) vascular anomalies (with one or more symptoms; epilepsy early in life, hemiparesis or hemiplegia, gyriform intracranial calci- fications and cerebral atrophy) and inconstant ipsilateral choroidal vascular lesions with glaucoma. • Portwine stain is usually unilateral, roughly involving the areas supplied by ophthalmic and maxillary divisions of trigeminal nerve, and bilateral in 50% of cases. • Portwine stains (naevus flammeus) are congenital vascular birthmarks that are present at birth and persist into adulthood. At birth, they are often pale pink macular lesions which with time, progress to become dark red to purple (Fig. 22.11) and even nodular. These changes occur as a result of progressive ectasia of cutaneous superficial vascular plexus. • Portwine stains can either occur as isolated cutaneous or be associated with structural abnormalities especially of those underlying the birth mark such as the choroidal vessels in the eye which produce glaucoma and leptomeningeal vessels in the brain which causes seizures, then is known as SWS.
  • 227. Genetics and Genodermatoses 219 Fig. 22.11: Sturge Weber syndrome—port wine nevus seen along ophthalmic and maxillary division of trigeminal nerve Xeroderma Pigmentosum (Pigmented Dry Skin) Itisanautosomalrecessivedisordercharacterized by photosensitivity, pigmentary changes, premature skin aging, neoplasia and abnormal DNA repair. • Eight different subtypes – complementation groups A to G and XP variants. • Main defect is in the DNA excision repair process (this is a process whereby damaged DNA is replaced with new DNA). • XP- variants have a normal nucleotide excision repair but the defect here is of a reduced molecular weight of newly synthesized DNA in UV radiated cells. Clinical Features • Skin normal at birth. • Earliest symptoms of dryness and freckling appear between six months and three years of age. • Freckles appear over face and hands, and later on neck, legs, lips and conjunctiva. Eventually freckles become permanent and progressively increase in number. • Continued sun exposure causes skin to become dry and parchment-like with pigmentation (hence the name xeroderma pigmentosum). • Next is the poikilodermatous stage characterized with atrophy and telangiectasia superadded to the existing freckles and hyperpigmentation (Fig. 22.12). • Superficial ulcers and atrophy may leave scars and contractures. • Ocular features include – photophobia with conjunctival injection, symblepharon, ectropion / entropion and loss of eye lashes due to atrophy of eyelid skin, keratitis leading to corneal opacity, pterygium and ocular neoplasms. Fig. 22.12: Xeroderma pigmentosum—freckle like pigmentation with atrophy, telangiectasia and actinic keratoses
  • 228. Essentials in Dermatology220 Fig. 22.13: Xeroderma pigmentosum—freckle like pigmentation with fungating squamous cell tumor of the face and scalp • Pre-malignant lesions like actinic keratosis and keratoacanthomas may occur in most cases. • Patients with XP under 20 years of age have a greater than 1000-fold increased risk of cutaneous basal cell or squamous cell carcinoma or melanoma (Fig. 22.13). The median age of onset of nonmelanoma skin cancer reported in patients with XP is 8 years. • Overall, there is a ten to twenty-fold increase ininternalneoplasms(centralnervoussystem, lung, gastric, breast, renal, etc.) in XP. • 20% have neurological complaints – mental retardation, areflexia, spasticity, ataxia, and sensorineural deafness. • Disease is often fatal under 10 years of age and two thirds of the cases die by 20 years of age. • De Sanctis –Cacchione syndrome consists of xeroderma pigmentosum, with microcephaly, mental deficiency, dwarfism, hypogonadism, choreoathetosis, and ataxia. • Prenatal diagnosis by amniocentesis is possible. • Differential diagnosis includes ordinary freckling, other causes of photosensitivity and premature ageing syndromes such as Rothmund-Thomson syndrome, Bloom syndrome,Cockaynesyndrome,progeria,and acrogeria. • Treatment: The mainstay of management is by ensuring maximum photoprotection (clothing,topicalandsystemicsunscreens,UV filter glasses). Ocular symptoms should be managed promptly to prevent complications. Early and adequate excision of all tumors is essential and topical 5-fluorouracil may be used for pre-malignant lesions. Oral retinoids have been found to decrease the occurrence of skin cancers in this condition. Incontinentia Pigmenti (Bloch-Sulzberger Disease) • Incontinentia pigmenti is an uncommon genodermatosis of the developing neuroectoderm in which vesicular, verrucous and pigmented lesions are associated with developmental defects of eye, skeletal system and central nervous system. • Incontinentia pigmenti is a complex hereditary syndrome that principally affects female infants. It is inherited as an X-linked dominant disorder, caused by mutation of NEMO gene on chromosome Xq28. The gene is generally lethal in male fetuses. • This multisystem disorder has manifestations of dermatological, neurological, skeletal, ocular or dental origin. • It manifests at birth or during first weeks of life. • In the skin, the disorder characteristically progresses through four stages. The first stage
  • 229. Genetics and Genodermatoses 221 Fig. 22.14: Incontinentia pigmenti – linear whorled vesicular eruption along Blashko’s lines over the lower limbs (vesicular phase) is characterized by linear whorled vesicular eruption along Blaschko’s lines (Fig. 22.14). The eruption typically favors acral locations. Peripheral leucocytosis and eosinophilia may occur during this stage. This stage is followed 2 to 6 weeks later by verrucous or lichenoid lesions on the sites of the former vesicular eruption in 30% of patients. The third stage (pigmentary phase) starts between 12th and 20th week and is characterized by hyperpigmented lesions. A fourth stage, rarely seen in some adult females is characterized by faint hypochromic or atrophic linear macules over extremities. The hair is usually normal, but in 25% of cases, cicatricial alopecia may be seen. • Incontinentia pigmenti achromians (hypomelanosis of Ito) suggest the negative image of incontinentia pigmenti characterized by unilateral or bilateral hypopigmentation along the lines of Blaschko. • Usually, no treatment is necessary other than the control of secondary infection.
  • 230. Essentials in Dermatology222 23 SKIN IN ENDOCRINE DISORDERS Hormones secreted by endocrine glands have physiological effects on pigmentation, hair growth, sebaceous glands and connective tissue. Endocrine disorders are associated with various cutaneous manifestations which offer clue to the diagnosis of the underlying endocrine disorder. SKIN IN PITUITARY DISORDERS Acromegaly: It results from excessive secretion of growth hormone by pituitary adenomas (98% of cases) in adolescents or adults. Patients are tall and have prognathism, frontal bossing, elongated, blunt and thickened fingers. Dermatological features include thickening of skin, accentuation of facial, neck and scalp creases imparting corrugated appearance (cutis verticis gyrata), widened triangular shaped nose, large ears, large and protruding lower lip, edematous thick eyelids, macroglossia, numerous skin tags (fibroma molluscum), seborrhea, acne, hyperhidrosis, hyperpigmentation, acanthosis nigricans, coarse scalp and body hair, wide and thickened nails. Panhypopituitarism: It results from destruction of pituitary gland from various causes (post partum hemorrhage “Sheehan’s syndrome”, adenoma, craniopharyngioma, tuberculosis, Skin in Systemic Diseases sarcoidosis, or iatrogenic) leading to multiple hormone deficiency. Cutaneous manifestations are non-specific and include xerotic skin, fine wrinkling around eyes and mouth, pallor, generalized hypopigmentation, increased sun- burn tendency, thinning of scalp and body hair, reduced sweat and sebaceous gland activity and thin brittle nails. SKIN IN ADRENAL SYNDROMES Cushing’s syndrome and Cushing’s disease: Cushing’s disease refers to hypercortisolism (glucocorticoid excess) from ACTH over- production, most commonly by pituitary adenoma, whereas Cushing’s syndrome refers to hypercortisolism, resulting from any cause, such as pituitary ACTH overproduction, ectopic ACTH production, or from adrenal adenoma, carcinoma or hyperplasia, or from glucocorticoid therapy. Skin is atrophic, smooth and transparent (paper thin), and there is facial fullness and plethora (moon facies), buffalo hump (Fig. 23.1), fullness of supraclavicular fossa, truncal obesity and relative lack of fat in lower extremities “lemon on stick appearance”, poor wound healing, striae particularly over abdomen, arms, and thighs, purpura, petechiae, easy bruising and purplish mottling (cutis marmorata), acneiform eruptions, hirsutism,
  • 231. Skin in Systemic Diseases 223 male pattern baldness in females, addisonian like pigmentation, and increased incidence of fungal infections. Addison’s disease (primary adrenal insuffi- ciency): It refers to insufficient secretion of adrenocortical hormones mainly cortisol and mineralocorticoids due to destruction of adrenal glands. Various causes of adrenal gland damage are autoimmune disorders in 70% of cases, tuberculosis, fungal infections, sarcoidosis, metastasis, and hemorrhage. Secondary adrenal insufficiency results from hypothalamic or pituitary diseases leading to decreased ACTH secretion, or steroid withdrawal after long term use. General features of Addison’s disease are fatigue, dizziness, anorexia, nausea, vomiting, diarrhea, abdominal pain and hypotension. Cutaneous findings are hyperpigmentation of skin due to elevated ACTH and MSH, mainly over light exposed areas, elbow, knee, knuckles, axillae, areolae, umbilicus, genitalia, palmar creases (Fig. 23.2), tongue and mucous membranes, scars, and nails. Fibrosis and calcification of ear may occur. Hyper- pigmentation is absent in secondary adrenal insufficiency (referred to as “white Addison’s disease). Pheochromocytoma: It is a rare adrenal tumor (mostly benign). Main clinical feature is hypertension, but can lead to flushing episodes. SKIN IN THYROID DISEASES Hyperthyroidism It may be a manifestation of Grave’s disease (most common cause), toxic multinodular goiter, adenoma, Hashimoto’s thyroiditis (early stage) and iatrogenic. Grave’s disease: It is an autoimmune disease characterized by antithyroid antibodies such as long acting thyroid stimulator (LATS). Skin is warm, moist and smooth, and there is facial flushing, palmar erythema, generalized hyperhidrosis more so on palms and soles, pruritis, urticaria, addisonian hyperpigmen- tation, hyperpigmentation of eyelid (Jellinek’s sign), and thyroid swelling in the neck. Scalp hair become fine, soft and friable, telogen effluvium can occur. Nails grow rapidly, become thin and soft, develop distal onycholysis (Plummer’s nails). In addition to these features of hyper- thyroidism, patients of Grave’s disease may have pretibial myxoedema, thyroid acropachy and exophthalmos (Diamond’s triad). Fig. 23.1: Cushing’s syndrome—buffalo hump Fig. 23.2: Addison’s disease—hyperpigmentation of palmar creases
  • 232. Essentials in Dermatology224 Pretibial myxoedema is characterized by bilateral asymmetric, firm, hyperpigmented, plaques or nodules, with orange peel texture (peau d’orange) mainly over shins and feet due to cutaneous accumulations of glycosamino- glycans (Fig. 23.3). Localized hypertrichosis and hyperhidrosis can occur over these lesions . Thyroid acropachy is characterized by digital clubbing, soft tissue swelling of hands and feet, and diaphyseal proliferation of periosteum in acral and distal long bones (tibia, fibula, ulna and radius). Exophthalmosis due to orbital deposits in orbital fossa, always bilateral. Autoimmune diseases such as vitiligo, alopecia areata can occur in association with Grave’s disease. Hypothyroidism (Myxoedema) Deficiency of thyroid hormone may be caused by Hashimoto’s thyroiditis, iodine deficiency, iatrogenic following total thyroidectomy, radioiodine therapy, drugs such as lithium, congenital hypothyroidism and secondary hypothyroidism due to reduced TSH from pituitary. The dermal manifestations are mainly due to accumulation of mucopolysaccharides (chondroitin sulphate and hyaluronic acid) in the skin. Skin appears rough, cool, dry, swollen, waxy and pale with increased skin creases, and there can be reduced sweating, asteatotic eczema, pruritis, and palmoplantar keratoderma (palms and soles, yellow-orange due to carotenemia). Patient may have characteristic expressionless facies with puffy and drooping eyelids, broad nose, swollen lips, and macroglossia. There is delayed wound healing, purpura, ecchymosis and xanthomatosis may occur. Nails grow slowly, become thick and brittle with longitudinal and transverse striations. Scalp and body hairs are sparse, coarse, dry and brittle, tend to fall out easily resulting in diffuse or partial alopecia. Loss of lateral third of eyebrows (madarosis) -Hertoghe’s sign In juvenile hypothyroids, waxy yellowish skin change is more prominent, but puffiness may be less apparent. In cretinism, infants will have periorbital puffiness, macroglossia, swollen hands and feet, cold and dry skin, cutis marmorata and umbilical hernia (pathognomonic). Unlike in adult hypothyroid, eyebrows tend to be confluent. SKIN IN PARATHYROID DISEASES Hyperparathyroidism Primarily occurs due to adenoma, hyperplasia or carcinoma of parathyroid glands and secondary due to chronic renal failure. Subcutaneous calcifications can present as linearly arranged white papules or as infiltrating plaques usually over large joints. Subcutaneous calcification and calciphylaxis mainly occur in secondary hyperparathyroidism. Fig. 23.3: Pretibial myxoedema—bilateral firm hyper- pigmented plaques with orange peel texture over shins
  • 233. Skin in Systemic Diseases 225 Hypoparathyroidism Congenital absence of glands (Di George’s syndrome), thyroid surgery, hemochromatosis, metastatic cancer, or idiopathic in origin may be its causes. Skin changes may be similar to that of hypothyroidism. The skin becomes dry, hyperkeratotic and puffy with sparse and coarse hair. Chloasma and pellagra like pigmentary changes can occur. Nails become opaque and brittle with transverse ridges. Impetigo herpetiformis, psoriatic flares and eczematous dermatitis have been associated with hypoparathyroidism. Normalization of serum calcium levels with calcium and vitamin D usually reverse skin abnormalities. SKIN IN DIABETES MELLITUS Diabetes mellitus (DM) is characterized by relative or absolute deficiency of insulin, leading to gross defects in glucose, fat and protein metabolism. Type I DM (Insulin dependant DM) is due to insulin insufficiency from antibody mediated destruction of beta cells of pancreas. Type II (Non-insulin dependant DM) results from hyperglycemia mainly due to peripheral insulin resistance. Nearly all patients with DM have some skin manifestations. For most manifestations the pathogenesis remains unknown, and others result from damage to vascular, neurologic or immune systems. Macro and microangiopathy contribute significantly to the cutaneous complications of DM. Cutaneous Manifestations of DM 1. Skin Infections DM patients are at higher risk of contracting bacterial and fungal infections when compared to normal population. Staphylococcal and streptococcal pyodermas (folliculitis, furuncle, carbuncle), malignant otitis externa (caused by Pseudomonas aeruginosa), necrotizing fasciitis, and clostridial gangrene occur more frequently in diabetics. Candida albicans is the most common pathogen, causing intertrigo, vulvovaginitis, balanitis, glossitis, angular cheilitis, paronychia and onychomycosis. Tinea pedis and onycho- mycosis of toe nails are common. Rhinocerebral mucormycosis, a fatal condition caused by mucor and rhizopus species occur more commonly in diabetics. 2. Markers of DM Acanthosis nigricans (AN) presents as brown to gray black papillomatous cutaneous thickening of the flexural areas including posterolateral neck (most common site), axillae, groin and abdominal folds. Affected area will have velvety appearance, and it may involve mucous membranes also. AN can also occur in association with obesity, internal malignancy and with drugs such as corticosteroids and estrogens. Fig. 23.4: Diabetes mellitus—generalized granuloma annulare
  • 234. Essentials in Dermatology226 Generalized granuloma annulare presents with numerous small annular plaques formed by 1-2 mm flesh colored papules (Fig. 23.4). These lesions are symmetric and appear more commonly over the abdomen, chest, thighs and extensor of elbows, most frequently in older adults. Necrobiosis lipoidica (NL) is a cutaneous disorder, often but not always associated with diabetes mellitus. Sixty to seventy percent of patients have DM, so patients presenting with NL should be investigated for DM. More commonly affects middle aged women. The skin lesions start as skin colored or brownish red papule which evolve slowly into well demarcated waxy plaque of variable size. They have sharply defined, broad violet red or pink, elevated border and depressed yellow-orange centre with telangiectasias. Ulcerations commonly occur within the plaques and heal slowly resulting in depressed scars. Almost always affects shins, but can involve thighs, trunk, and face, scalp (scarring alopecia). Rarely disseminated NL can occur called as granulomatous disciformis chronica and progressiva. Bullosis diabeticorum is characterized by abrupt onset of bullae, mainly over the lower legs, feet, toes, and occasionally over dorsa of hands and fingers. Bullae appear over non inflamed skin, and measured from few millimeter to 3-5 cm in size, non-pruritic and painless. Healing occurs within 2 to 5 weeks and rarely leaves scar. Pathogenesis of bulla formation is unknown. Increased skin fragility due to glycosylation end products may be involved. Scleredema diabeticorum is characterized by insidious onset of painless, symmetric induration of skin and subcutaneous tissue mainly over upper back, neck, and rarely face, shoulder and anterior torso. Skin has non pitting, woody, “peau d’ orange” quality. There is decreased sensation to pain and light touch over the affected area, and decreased range of movements in neck and upper extremities. Most patients have type II diabetes. It is due to thickening of collagen bundles and deposition of glycosaminoglycans (mainly hyaluronic acid). 3. Complications of Diabetes Macroangiopathy Atherosclerosis induced by DM can lead to ischemic gangrenous changes in legs and feet, hypothermia, dry skin and nail dystrophy. Microangiopathy Microangiopathy causes many cutaneous manifestations, which include: 1. Wet gangrene of foot–occurs as a late complication. 2. Erysipelas like erythema–well demarcated, red areas occur on the legs or feet usually in elderly diabetics. 3. Diabetic rubeosis-peculiar rosy reddening of the face, rarely of hands and feet in long standing diabetics. 4. Diabetic dermopathy (diabetic shin spots or Binkley spots)— Most common dermatosis associated with diabetes. They start as crops of asymptomatic, oval, dull red papules 0.5-1cm in diameter, which gradually evolve into atrophic hyperpigmented lesions mainly over shins, also over forearms, thighs and bony prominences. If 4 or more are present, the specificity is high for microvascular disease in other tissues. An association seems to exist between dermopathy and other serious complications such as retinopathy, nephropathy and neuropathy. Diabetic Neuropathy And Diabetic Foot Diabetic foot is mainly caused by peripheral neuropathy but micro and macroangiopathy and infections also contribute. Diabetic neuropathy
  • 235. Skin in Systemic Diseases 227 is usually distal, polyneuritic, sensory and motor neuropathy. Motor neuropathy causes weakness and wasting of muscles, thereby uneven pressure on feet while walking. Sensory neuropathy predisposes to trauma and autonomic involvement causes hypohidrosis. All these factors combine to produce neurotrophic ulcers mainly over bony prominences; most commonly over the ball of great toe. The ulcer is usually painless, circular and punched out surrounded by a ring of callus. Some patients present with burning sensation in the feet. 4. Skin Diseases Commonly Associated with Diabetes Eruptive xanthomas, skin tags, vitiligo, lichen planus, acquired perforating disorders such as Kyrle’s disease, reactive perforating collagenosis, uremic pruritis occur commonly in association with diabetics. 5. Complications of Diabetic Therapy Oral hypoglycemic agents may produce allergic reactions, and photosensivity. Insulin causes erythema, urticaria and lipodystrophy at injection site. SKIN IN PRIMARY SYSTEMIC AMYLOIDOSIS Primary systemic amyloidosis involves mesenchymal tissue, the tongue, heart, gastrointestinal tract and skin. Cutaneous manifestations occur in approximately 40% of cases of primary systemic amyloidosis. The cutaneous eruptions usually begin as shiny, smooth, firm, flat topped or spherical papules of waxy color and have the appearance of transluscent vesicles because of their tenseness. These lesions coalesce to form nodules and plaques of various sizes. The regions about the eyes, nose, mouth and mucocutaneous junctions are commonly involved. Purpuric lesions and ecchymoses resultant of infiltration of blood vessels, chiefly affect the eyelids, limbs and oral cavity. Purpura typically occurs after trauma (pinch purpura). Purpuric lesions also classically appear after actions or procedures that result in increased pressure in the vessels of the face such as after proctoscopic examination. Glossitis with macroglossia may be an early symptom and can lead to dysphagia. The tongue becomes greatly enlarged and furrows develop. The lateral aspects show indentations from the teeth (Fig. 23.5). Diagnosis is confirmed by evaluation of patient’s serum and urine for immunoglobulin fragments and by demonstration of amyloid deposits in the skin. SKIN IN VASCULITIS The term vasculitis refers to inflammation and necrosis of blood vessels. The vasculitides are best classified according to the size of the involved vessels into large, medium and small vessel vasculitis. Classification of the Vasculitides A. Large Vessel Vasculitis 1. Giant cell arteritis 2. Takayasu arteritis Fig. 23.5: Systemic amyloidosis—macroglossia showing indentations of the tongue with gum hyperplasia
  • 236. Essentials in Dermatology228 B. Medium-sized Vessel Vasculitis 1. Kawasaki disease 2. Polyarterites nodosa (PAN) 3. Benign cutaneous PAN C. Small Vessel Vasculitis 1. Henoch-Schönlein purpura 2. Cutaneous leukocytoclastic angiitis 3. Microscopic polyangiitis 4. Wegener’s granulomatosis 5. Churg – Strauss syndrome Blood vessels have limited ways of responding to vessel wall injury. They may respond with increased permeability that leads to edema and purpura, attenuation of the vessel wall lead to aneurysm formation or hemorrhage, and intimal proliferation or thrombosis may cause stenosis or occlusion with tissue ischemia or infarction. The definitive diagnosis of a specific “vasculitis” remains dependent upon histopathologic confirmation of vasculitis in conjunction with the appropriate clinical picture and the exclusion of diseases that can cause secondary vascular inflammation such as infection (e.g., meningococcemia, gonococcemia, and endocarditis). The principal clinical clue to diagnosis of a specific vasculitic disorder is the pattern of organ involvement. Identification of qualitative pathologic changes in affected organs (pattern of necrosis, presence of granulomas, eosinophilic infiltration) further delineates the differential diagnosis. The identification of a vasculitic disorder may not always be easy because of the varied clinical presentations. More than one system is often involved and the manifestations can, therefore, be very heterogenous. However, there are some clinical pointers that may suggest the presence of a vasculitic disorder. These are- 1. Prolonged fever of unknown origin. 2. Suggestive skin lesions e.g. palpable purpura (Fig. 23.6), gangrene. 3. Unexplained peripheral neuropathy especially mononeuritis multiplex. 4. Arthralgia/arthritis, myositis, serositis. 5. Obscure pulmonary, cardiovascular or renal disease especially when there is multi-system involvement. 6. Laboratory parameters indicative of ongoing inflammation: e.g. leukocytosis, elevated ESR/CRP, eosinophilia, hypocomplemen- temia, cryoglobulinemia, circulating immune complexes. Kawasaki disease and Henöch-Schonlein purpura are the commonest vasculitides seen in children while giant cell arteritis, polyarteritis nodosa and Wegener’s granulomatosis are more common in the adults. Giant Cell Arteritis (GCA) GCA generally affects individuals older than 50 years of age and is variably associated with fever, headache, masticatory muscle claudication, peripheral vascular disease, inflammatory aortic aneurysms, and retinal Fig. 23.6: Vasculitis—palpable purpuric lesions over the legs of hypersensitivity vasculitis
  • 237. Skin in Systemic Diseases 229 ischemic syndromes. Cutaneous manifestations include rare cases of scalp or tongue ischemia and necrosis. The diagnosis is established by biopsy of the superficial temporal artery, which shows chronic mononuclear cell infiltrate, and giant cells. Takayasu Arteritis (TA) TA is a chronic, idiopathic inflammatory disease primarily affecting the large vessels, such as the aorta and its branches. It is also known as ‘pulseless disease’ and ‘reverse coarctation’. TA is more commonly associated with aortic and aortic branch vessel stenoses and aneurysms than GCA. TA is the most common cause of giant cell arteritis in young patients. It mainly affects females in the age group of 10-30 years. The precise etiology of TA is still unknown. The most common complaints at the onset of the disease include headache, dyspnea, palpitations, arthralgia/ arthritis and myalgia. Constitutional features can be in the form of fever, night sweats, weight loss and anorexia which may be seen in >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 non- thrombocytopenic 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.
  • 238. Essentials in Dermatology230 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, gastro- intestinal 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 gravity- dependent 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 discolor- ation—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 Henoch- Schönellein Purpura. Microscopic Polyangiitis Microscopic polyangiitis (MPA) involves vessels ranging in size from capillaries and venules to medium-sized arteries. Glomerulonephritis, especially rapidly progressive glomerulone- phritis, and alveolar hemorrhage are particularly common in MPA and uncommon in PAN. Antibody to myeloperoxidase, a type of P- ANCA, 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.
  • 239. Skin in Systemic Diseases 231 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 glomer- ulonephritis. 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, glomeru- lonephritis, 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 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