Andrews’ Diseases OFSkin THE Clinical Dermatology Commissioning Editor: Russell Gabbedy Development Editor: Sven Pinczewski Editorial Assistant: Kirsten Lowson / Rachael Harrison Project Manager: Elouise Ball Design: Stewart Larking Illustration Manager: Gillian Richards Illustrator: Richard Tibbits, Richard Prime Marketing Manager: Helena Mutak Andrews’ Diseases Skin OF THE Clinical Dermatology Eleventh Edition William D James, Timothy G Berger, MD MD Paul R Gross Professor of Dermatology Professor of Clinical Dermatology Department of Dermatology Executive Vice Chair and Residency University of Pennsylvania School of Program Director Medicine Chair in Dermatology Medical Student Philadelphia, Pennsylvania Education USA University of California, San Francisco San Francisco, California Dirk M Elston, USA MD Director Department of Dermatology Geisinger Medical Center Danville, Pennsylvania USA For additional online content visit www.expertconsult.com is an imprint of Elsevier Inc. © 2011, Elsevier Inc. All rights reserved. 10th edition © 2006, Saunders Elsevier No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Rights Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: [email protected]. You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/ permissions. ISBN: 978-1-4377-0314-6 International ISBN: 978-0-8089-2417-3 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Notice Medical knowledge is constantly changing. Standard safety precautions must be followed, but as new research and clinical experience broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual patient. Neither the Publisher nor the author assume any liability for any injury and/or damage to persons or property arising from this publication. The Publisher Working together to grow libraries in developing countries www.elsevier.com | www.bookaid.org | www.sabre.org James, William D. (William Daniel), 1950– Andrews’ Diseases of the skin : clinical dermatology. — 11th ed. 1. Skin—Diseases. 2. Dermatology. I. Title II. Diseases of the skin III. Elston, Dirk M. IV. Berger, Timothy G. V. Andrews, George Clinton, 1891-1978. Diseases of the skin. 616.5—dc22 The publisher’s policy is to use paper manufactured from sustainable forests Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 PREFACE AND ACKNOWLEDGEMENTS Andrews’ remains as it was from the beginning: an authored Molecular investigative techniques, technologic break- text whose one volume is filled with clinical signs, symptoms, throughs, and designer therapeutics lead the way in providing diagnostic tests, and therapeutic pearls. The authors have advances in our specialty. We cover the new understanding remained general clinical dermatologists in an era of subspe- following from such innovations by discussing the mecha- cialists in academia. They are committed to keeping Andrews’ nisms at work in genetic diseases, covering the latest in der- as an excellent tool for anyone who needs help in diagnosing matopathologic staining and analysis, adding a second chapter a patient with a clinical conundrum or treating a patient with on cosmetic surgery, and enlarging the therapeutic recom- a therapeutically challenging disease. mendations to include our expanded therapeutic options, such Andrews’ is primarily intended for the practicing dermatolo- as biologic response modifiers, and biologically engineered gist. It is meant to be used on the desktop at his or her clinic, targeted medications. We have attempted to define therapeu- giving consistent, concise advice on the whole gamut of clini- tics in a fashion that emphasizes those interventions with the cal situations faced in the course of a busy workday. While we highest level of evidence, but also present less critically inves- have been true to our commitment to a single-volume work, tigated therapeutic options. To care for our patients we need we provide our text in a convenient online format as well. a large array of options. Not all are fully supported by formal Because of its relative brevity but complete coverage of our evidence, yet are helpful to individual patients. field, many find the text ideal for learning dermatology the Extensive revisions were necessary to add this wealth of new first time. It has been a mainstay of the resident yearly curricu- information. We selectively discarded older concepts. By elimi- lum for many programs. We are hopeful that trainees will nating older, not currently useful information we maintain the learn clinical dermatology by studying the clinical descrip- brief but complete one-volume presentation that we and all tions, disease classifications, and treatment insights that define previous authors have emphasized. Additionally, older refer- Andrews’. We believe that students, interns, internists or other ences have been updated. The classic early works are not cited; medical specialists, family practitioners, and other health pro- instead we have chosen to include only new citations and let fessionals who desire a comprehensive dermatology textbook the bibliographies of the current work provide the older refer- will find that ours meets their needs. Long-time dermatolo- ences as you need them. A major effort in this edition was to gists will hopefully discover Andrews’ to be the needed update reillustrate the text with 567 new color images. Many have that satisfies their lifelong learning desires. On our collective been added to the printed text; you will also find a large trips around the world, we have been gratified to see our number only in the online version. Enjoy! We have looked to international colleagues studying Andrews’. Several thousand our own collections to accomplish this. These are the result of books have been purchased by Chinese and Brazilian derma- many hours of personal effort, the generosity of our patients, tologists alone. and a large number of residents and faculty of the programs Many major changes have been made to this edition. Bill in which we currently work or have worked in the past. James, Tim Berger and Dirk Elston, three great friends of Additionally, friends and colleagues from all parts of the globe nearly three decades, have worked closely to continue to have allowed us to utilize their photographs. They have given improve the quality of our text. The surgical chapters have their permission for use of these wonderful educational photos been updated and expanded by Isaac Neuhaus. We thank him to enhance your understanding of dermatology and how these for his efforts to enhance the procedural portion of our text- diseases affect our patients. We cannot thank them enough. book and acknowledge the contributions of Roy Grekin in All of the authors recognize the importance of our mentors, prior editions. We have tried to ensure that each entity is only teachers, colleagues, residents, and patients in forming our discussed once, in a complete yet concise manner. In order to collective expertise in dermatology. Dirk, Tim and Bill were do this we have had to make decisions regarding the place- all trained in military programs, and our indebtedness to this ment of disease processes in only one site. Clearly, neutrophilic fellowship of clinicians is unbounded. The many institutions eccrine hidradenitis, for example, could be presented under we have called home, from the East Coast of Walter Reed, to drug eruptions, neutrophilic reactive conditions, infection or the West Coast of the University of California at San Francisco, cancer-associated disease, or with eccrine disorders. The final and many in between, such as Brooke in San Antonio and the decisions were a team effort and made in the interest of elimi- Cleveland Clinic, nurtured us and expanded our horizons. nating redundancy. This allows us to present our unified phi- Our friendship goes well beyond the limits of our profession; losophy in treating patients in one dense volume. it is wonderful to work with people you not only respect as Medical science continues to progress with break-neck colleagues, but also enjoy as closely as family. Finally we are speed. Our understanding of the etiology of certain conditions proud to be a part of the Elsevier team and have such profes- has now led us to recategorize well-recognized disease states sionals as Claire Bonnett, Sven Pinczewski, Elouise Ball, and and dictated the addition over 70 newly described entities. Russell Gabbedy supporting us every step of the way. vi DEDICATION For my family, whose love and support sustain me and make me happy. Bill D James My wife Jessica and my children, Olivia and Mateo, who give me the joy and strength to undertake such a task. Tim G Berger To my wife and best friend, Kathy, and our wonderful chil- dren, Carly and Nate. Dirk M Elston The authors: William D James, Timothy G Berger, Dirk M Elston. vii CONTRIBUTOR Isaac M Neuhaus, MD Assistant Professor Dermatologic Surgery and Laser Center University of California, San Francisco San Francisco, California USA viii Bonus images for this chapter can be found online at http://www.expertconsult.com 1 Skin: Basic Structure and Function Skin is composed of three layers: the epidermis, dermis, and consist of two subfamilies, acidic and basic. The product of one subcutaneous fat (panniculus) (Fig. 1-1). The outermost layer, basic and one acidic keratin gene combines to form the multi- the epidermis, is composed of viable keratinocytes covered by ple keratins that occur in many tissues. The presence of various a layer of keratin, the stratum corneum. The principal compo- keratin types is used as a marker for the type and degree of nent of the dermis is the fibrillar structural protein collagen. differentiation of a population of keratinocytes. Keratins are The dermis lies on the panniculus, which is composed of critical for normal functioning of the epidermis and keratin lobules of lipocytes separated by collagenous septae that mutations are recognized causes of skin disease. Mutations in contain the neurovascular bundles. the genes for keratins 5 and 14 are associated with epidermo- There is considerable regional variation in the relative thick- lysis bullosa simplex. Keratin 1 and 10 mutations are associ- ness of these layers. The epidermis is thickest on the palms ated with epidermolytic hyperkeratosis. Mild forms of this and soles, measuring approximately 1.5 mm. It is very thin on disorder may represent localized or widespread expressions the eyelid, where it measures less than 0.1 mm. The dermis is of mosaicism for these gene mutations. thickest on the back, where it is 30–40 times as thick as the The epidermis may be divided into the following zones, overlying epidermis. The amount of subcutaneous fat is gener- beginning with the innermost layer: basal layer (stratum ger- ous on the abdomen and buttocks compared with the nose and minativum), Malpighian or prickle layer (stratum spinosum), sternum, where it is meager. granular layer (stratum granulosum), and horny layer (stratum corneum). On the palms and soles a pale clear to pink layer, the stratum lucidum, is noted just above the granular layer. Epidermis and adnexa When the skin in other sites is scratched or rubbed, the Malpighian and granular layers thicken, a stratum lucidum During the first weeks of life, the fetus is covered by a layer forms, and the stratum corneum becomes thick and compact. of nonkeratinizing cuboidal cells called the periderm (Fig. 1-2). Histones appear to regulate epidermal differentiation and Later, the periderm is replaced by a multilayered epidermis. histone deacetylation suppresses expression of profilaggrin. Adnexal structures, particularly follicles and eccrine sweat Slow-cycling stem cells provide a reservoir for regeneration of units, originate during the third month of fetal life as down- the epidermis. Sites rich in stem cells include the deepest por- growths from the developing epidermis. Later, apocrine sweat tions of the rete, especially on palmoplantar skin, as well as units develop from the upper portion of the follicular epithe- the hair bulge. Stem cells divide infrequently in normal skin, lium and sebaceous glands from the midregion of the follicle. but in cell culture they form active growing colonies. They can Adnexal structures appear first in the cephalic portion of the be identified by their high expression of β1-integrins and lack fetus and later in the caudal portions. of terminal differentiation markers. Stem cells can also be The adult epidermis is composed of three basic cell types: identified by their low levels of desmosomal proteins, such as keratinocytes, melanocytes, and Langerhans cells. An addi- desmoglein 3. The basal cells divide and, as their progeny tional cell, the Merkel cell, can be found in the basal layer of move upward, they flatten and their nucleus disappears. the palms and soles, oral and genital mucosa, nail bed, and Abnormal keratinization can manifest as parakeratosis follicular infundibula. Merkel cells, located directly above the (retained nuclei), as corps ronds (round, clear to pink, abnor- basement membrane zone, contain intracytoplasmic dense- mally keratinized cells), or as grains (elongated, basophilic, core neurosecretory-like granules, and, through their associa- abnormally keratinized cells). tion with neurites, act as slow-adapting touch receptors. They During keratinization, the keratinocyte first passes through have direct connections with adjacent keratinocytes by desmo- a synthetic and then a degradative phase on its way to becom- somes and contain a paranuclear whorl of intermediate keratin ing a horn cell. In the synthetic phase, the keratinocyte accu- filaments. Both polyclonal keratin immunostains and mono- mulates within its cytoplasm intermediate filaments composed clonal immunostaining for keratin 20 stain this whorl of of a fibrous protein, keratin, arranged in an alpha-helical keratin filaments in a characteristic paranuclear dot pattern. coiled coil pattern. These tonofilaments are fashioned into Merkel cells also label for neuroendocrine markers such as bundles, which converge on and terminate at the plasma chromogranin and synaptophysin. membrane, where they end in specialized attachment plates called desmosomes. The degradative phase of keratinization Keratinocytes is characterized by the disappearance of cell organelles and the consolidation of all contents into a mixture of filaments Keratinocytes, or squamous cells, are the principal cells of the and amorphous cell envelopes. This programmed process of epidermis. They are of ectodermal origin and have the special- maturation resulting in death of the cell is termed terminal ized function of producing keratin, a complex filamentous differentiation. Terminal differentiation is also seen in the protein that not only forms the surface coat (stratum corneum) involuting stage of keratoacanthomas, where the initial phase of the epidermis but also is the structural protein of hair and of proliferation gives way to terminal keratinization and nails. Multiple distinct keratin genes have been identified and involution.