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Description

Save time diagnosing skin diseases with Dermatopathology, edited by Drs. Nooshin Brinster, Vincent Liu, Hafeez Diwan, and Phillip McKee. Part of the High-Yield Pathology Series, this title is designed to help you review the key pathologic features of skin disease, recognize the classic look of each disease, and quickly confirm your diagnosis. Its templated format, excellent color photographs, concise bulleted text, and authoritative content, will help you accurately identify more than 400 skin conditions.

  • Find information quickly and easily with a templated, easy-to-reference format.
  • Confirm your diagnoses with excellent color photographs that demonstrate the classic appearance of each disease.
  • Find the answers you need fast with concise bulleted text.
  • Depend on authoritative information from leading experts in the field.

Sujets

Ebooks
Savoirs
Medecine
Médecine
Acné rosacea
Mycetoma
Balanitis plasmacellularis
Scleredema
Necrobiotic xanthogranuloma
Phaeohyphomycosis
Pityrosporum folliculitis
Colloid milium
Urticarial vasculitis
Cutaneous small-vessel vasculitis
Pancreatic panniculitis
Lichen striatus
Erythema dyschromicum perstans
Inflammatory linear verrucous epidermal nevus
Eosinophilic cellulitis
IgA pemphigus
Porokeratosis
Linear IgA bullous dermatosis
Fixed drug reaction
Acute generalized exanthematous pustulosis
Herpes simplex
Drug-induced lichenoid reaction
Transient neonatal pustular melanosis
Alopecia mucinosa
Neutrophilic eccrine hidradenitis
Chondrodermatitis nodularis chronica helicis
Reactive perforating collagenosis
Elastosis perforans serpiginosa
Lupus erythematosus panniculitis
Epidermolysis bullosa acquisita
Pemphigus vegetans
Pemphigus erythematosus
Pemphigus foliaceus
Pseudoporphyria
Lipodermatosclerosis
Dermatitis herpetiformis
Rhinosporidiosis
Ecthyma
Mucormycosis
Lupus erythematosus
Erythema elevatum diutinum
Rheumatoid nodule
Lichen nitidus
Verruca plana
Nephrogenic systemic fibrosis
Cicatricial pemphigoid
Gestational pemphigoid
Transient acantholytic dermatosis
Papular mucinosis
Subcutaneous fat necrosis of the newborn
Pityriasis lichenoides
Bacillary angiomatosis
Aspergillosis
Erythema annulare centrifugum
Necrolytic migratory erythema
Calciphylaxis
Radiation dermatitis
Hailey?Hailey disease
Androgenic alopecia
Granuloma annulare
Keratosis follicularis
Degos disease
Pretibial myxedema
Protothecosis
Necrobiosis lipoidica
Morphea
Sweet's syndrome
Lupus vulgaris
Pseudoxanthoma elasticum
Polymorphous light eruption
Erythema nodosum
Bullous pemphigoid
Nodular vasculitis
Atopic dermatitis
Dermatophytosis
Pityriasis rubra pilaris
Meleda disease
Chromoblastomycosis
Coagulopathy
X-linked ichthyosis
Dyshidrosis
Granuloma faciale
Cryoglobulinemia
Actinomycosis
Actinic keratosis
Stasis dermatitis
Condyloma
Lichen sclerosus
Pityriasis rosea
Polyarteritis nodosa
Calcinosis cutis
Dermatomyositis
Erythema multiforme
Toxic epidermal necrolysis
Coumadin
Urticaria
Lichen planopilaris
Lichen planus
Blastomycosis
Henoch?Schönlein purpura
Axilla
Cellulitis
Atrophy
Panniculitis
Epidermolysis bullosa
Epidermolytic hyperkeratosis
Lamellar ichthyosis
Ichthyosis vulgaris
Hidradenitis suppurativa
Graft-versus-host disease
Chilblains
Porphyria cutanea tarda
Seborrhoeic dermatitis
Folliculitis
Granuloma inguinale
Sarcoptes scabiei
Histoplasmosis
Plantar wart
Alpha 1-antitrypsin deficiency
Varicella zoster virus
Necrotizing fasciitis
Sarcoidosis
Orf (disease)
Neutrophil granulocyte
Antiphospholipid syndrome
Schistosomiasis
Coccidioidomycosis
Alopecia areata
Embolism
Keloid
Impetigo
Acne vulgaris
Crohn's disease
Infection
Wart
Giant cell arteritis
Systemic scleroderma
Cholesterol
Beryllium
Pyoderma gangrenosum
Pemphigus
Gout
Molluscum contagiosum
Pustule
Candida
Purpura
Anthrax
Lymphocyte
Psoriasis

Informations

Publié par
Date de parution 06 janvier 2011
Nombre de lectures 0
EAN13 9781455706235
Langue English
Poids de l'ouvrage 11 Mo

Informations légales : prix de location à la page 0,0620€. Cette information est donnée uniquement à titre indicatif conformément à la législation en vigueur.

Exrait

Dermatopathology
High-Yield Pathology

Nooshin K. Brinster, MD
Assistant Professor, Departments of Pathology and Dermatology, Director of Dermatopathology Services, Virgina Commonwealth University Medical Center, Richmond, Virginia

Vincent Liu, MD
Clinical Associate Professor, Departments of Dermatology and Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa

A. Hafeez Diwan, MD, PhD
Associate Professor and Director of Dermatopathology, Departments of Pathology & Immunology and Dermatology, Baylor College of Medicine, Houston, Texas

Phillip H. McKee, MD, FRCPath
Formerly Associate Professor of Pathology and Director, Division of Dermatopathology, Department of Surgical Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
Saunders
Front Matter

High-Yield Pathology Dermatopathology
Nooshin K. Brinster, MD
Assistant Professor, Departments of Pathology and Dermatology, Director of Dermatopathology Services, Virgina Commonwealth University Medical Center, Richmond, Virginia
Vincent Liu, MD
Clinical Associate Professor, Departments of Dermatology and Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa
A. Hafeez Diwan, MD, PhD
Associate Professor and Director of Dermatopathology, Departments of Pathology & Immunology and Dermatology, Baylor College of Medicine, Houston, Texas
Phillip H. McKee, MD, FRCPath
Formerly Associate Professor of Pathology and, Director, Division of Dermatopathology, Department of Surgical Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Copyright

1600 John F. Kennedy Blvd.
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DERMATOPATHOLOGY ISBN: 978-1-4160-9976-5
Copyright © 2011 by Saunders, an imprint of Elsevier Inc .
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. Details on how to seek permission, further information about the Publisher's permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions .
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notice
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
Library of Congress Cataloging-in-Publication Data or Control Number
Dermatopathology/Nooshin K. Brinster… [et al.].
p.; cm. -- (High-yield pathology)
Includes index.
ISBN 978-1-4160-9976-5 (hardcover: alk. paper)
1. Skin--Diseases--Handbooks, manuals, etc. 2. Skin--Pathophysiology--Handbooks, manuals, etc. I. Brinster, Nooshin K. II. Series: High-yield pathology.
[DNLM: 1. Skin Diseases--Handbooks. 2. Skin--pathology--Handbooks. WR 39 H638 2010]
RL95.D52 2010
616.5’071--dc22 2010019232
Publishing Director: William Schmitt
Senior Developmental Editor: Andrew Hall
Publishing Services Manager: Patricia Tannian
Team Manager: Radhika Pallamparthy
Senior Project Manager: Kristine Feeherty
Project Manager: Antony Prince
Design Direction: Steven Stave
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Dedication
To my love, Derek, and our four smiling faces: Layla, Maya, Neda, and Ella. No matter what …

Nooshin Brinster
To my absolutely wonderful wife, Saba, my two children, my parents, and my three sisters.

Hafeez Diwan
To all the patients who grace us, the teachers who inspire us, the students who challenge us, and the families who fulfill us, this book is for you.

Vince Liu
To Gracie and my four children, whose lives revolve around dermatopathology!

Phillip McKee
Preface
High-Yield Pathology, with access to ExpertConsult.com , is a new series of pathology textbooks providing quick reference for the busy pathologist and student. We are honored to have this dermatopathology textbook as the first volume in the series.
The study of dermatopathology requires appreciation and understanding of the “gross” disease, that is, the clinical aspect of cutaneous disorders, as well as the histological findings. By integrating both pathological and clinical features, one is able to arrive at a meaningful diagnosis. With this in mind, Dermatopathology is organized by histological patterns, further classified by disease entity. Clinical and pathological features of each entity are presented and, where relevant, clinical photographs are provided. Several pathological photographs are included of each disease, including immunohistochemical and immunofluorescence, to illustrate the many faces and phases of each disease. Furthermore, the text is presented in a bulleted format to facilitate quick reference and learning at the microscope. We hope that it will provide valuable and practical information for general pathologists, dermatopathologists, and residents and fellows alike.

Nooshin K. Brinster, MD

Vincent Liu, MD

A. Hafeez Diwan, MD, PhD

Phillip H. McKee, MD, FRCPath
Acknowledgments
Dermatopathology is a book whose creation and fulfillment would not have been possible without the unwavering leadership of Phillip McKee. His highest standards and immeasurable dedication are inspiring and matched only by his passion and sense of humor. It has been a gift to work with and learn from a master. I am also thankful to my old friend, Vince Liu, who invited me to join the project.
I am in debt to the dermatology residents and faculty of the Medical College of Virginia who have provided me with the many clinical photographs and skin biopsies that have found their way into this textbook. I have also been fortunate to have the administrative support of Jeanette MacFarland and Carol Burney, who have always been ready to help, however short the notice may have been.
I am extremely grateful to the group at Elsevier publishing, including William Schmitt, publishing director; Andrew Hall, developmental editor; Kristine Feeherty, project manager; and Steve Stave, manager of design.
The support of my family has been critical. My parents, Masoud and Vida, have championed my every endeavor, from childhood until today, with much love. I am most grateful for the love and guidance of my beloved husband, Derek, and for our dear daughters, Layla, Maya, Neda, and Ella. They have tolerated the many long hours (mostly after bedtime) spent in writing the book. I am particularly thankful that our latest addition demonstrated an uncanny sense of timing by delaying her arrival into this world until the book was complete.

Nooshin K. Brinster
A work of this kind does not happen without the help of many. First, I am grateful for all the patients I have been privileged to have known. Second, I am indebted to all those who have taught me the art and science of dermatology and dermatopathology. Third, I owe a great deal to all the medical students, residents, and fellows who have inspired my appreciation for teaching. Fourth, many thanks go to Chris Huber for her invaluable secretarial assistance. And finally, for her unflagging support through the tremendous sacrifice of this endeavor, a special thank you to Paula.

Vince Liu
I would like to thank the following colleagues and friends for their help: Jonathan Curry, Doina S. Ivan, Alexander J. Lazar, Daniel Ostler, Jose Plaza, Victor G. Prieto, Ronald P. Rapini, Carlos Torres-Cabala, Wei Lien-Wang, and Darren Whittemore. Doina Ivan was especially helpful in the preparation of the chapter on Cutaneous Metastases—she added significantly to, and vastly improved, this section. And a special thanks to Saba, Sara, and Hasan, who tolerated and supported me on many weekends and evenings when I was doing my Greta Garbo impersonation, wanting to be alone for extended periods of time to work on this book.

Hafeez Diwan
I am indebted to Bill Schmitt from Elsevier, who first thought of this concept, and to Andy Hall (also of Elsevier), whose patience and support throughout the preparation of this book have been unwavering. It has been a pleasure working on the project with Nooshin, Vince, and Hafeez, although my role has been limited to editing (sometimes quite a lot!) and photography. As always, I learn much from others. I also am extremely grateful to Eduardo Calonje, Alex Lazar, Thomas Brenn, Wayne Grayson, and Iskander Chaudhry, who continually supply me with fascinating cases to study and photographs for the various book projects that dominate my life. Finally and of greatest importance, I would never achieve anything if it were not for the patience and support of Gracie, who―in addition to being my wife, soul mate, and closest of friends―never wavers in her uphill battle of keeping me on the right path. Sometimes she finds this a Herculean task!

Phillip McKee
The authors are grateful to the following friends who so kindly contributed cases: M Avram, F Awadalla, D Barber, C Baum, M Blanes, T Brenn, E Calonje, I Chaudhry, J Cohen, G Dorer, L Edsall, A Farrajoli, S Granter, W Grayson, B Horvath, E Hudgins, D Jones, B Kockentiet, A Lazar, PE LeBoit, S Lyle, M Maiberger, SR Mays, F McMullen, D Metze, M Michal, J Nunley, JC Pascual, S Peck, L Requena, M Saeb, A Schiedel, D Slater, B Swick, I Van den Berghe, K Vu, D Whittemore, S-B Woo, L Yarbrough, and B Zelger.
The authors also thank the late NP Smith.
Table of Contents
Front Matter
Copyright
Dedication
Preface
Acknowledgments
I: Inflammatory Dermatitis
A: Spongiotic Dermatitis
Chapter 1: Atopic Dermatitis
Chapter 2: Seborrheic Dermatitis
Chapter 3: Allergic Contact Dermatitis
Chapter 4: Dyshidrotic Eczema (Pompholyx)
Chapter 5: Stasis Dermatitis
Chapter 6: Spongiotic Drug Eruption
Chapter 7: Arthropod Bite Reaction
Chapter 8: Incontinentia Pigmenti (Bloch-Sulzberger Syndrome)
Chapter 9: Pityriasis Rosea
Chapter 10: Photosensitive (Phototoxic/Photoallergic) Dermatitis
B: Psoriasiform and Pustular Dermatitis
Chapter 11: Psoriasis
Chapter 12: Reiter’s Syndrome
Chapter 13: Pityriasis Rubra Pilaris
Chapter 14: Subcorneal Pustular Dermatosis
Chapter 15: Acute Generalized Exanthematous Pustulosis
Chapter 16: Transient Neonatal Pustular Melanosis
Chapter 17: Lichen Simplex Chronicus and Prurigo Nodularis
Chapter 18: Inflammatory Linear Verrucous Epidermal Nevus
C: Interface Dermatitis
Chapter 19: Erythema Multiforme
Chapter 20: Toxic Epidermal Necrolysis/Stevens-Johnson Syndrome
Chapter 21: Lupus Erythematosus
Chapter 22: Dermatomyositis
Chapter 23: Graft-Versus-Host Disease (GVHD)
Chapter 24: Interface Dermatitis of HIV Infection
Chapter 25: Pityriasis Lichenoides
D: Lichenoid Dermatitis
Chapter 26: Lichen Planus
Chapter 27: Lichenoid Drug Reaction
Chapter 28: Fixed Drug Eruption
Chapter 29: Lichen Striatus
Chapter 30: Lichen Nitidus
Chapter 31: Erythema Dyschromicum Perstans (Ashy Dermatosis)
Chapter 32: Lichenoid Keratosis
E: Acantholytic Disorders
Chapter 33: Pemphigus Foliaceus
Chapter 34: Pemphigus Erythematosus
Chapter 35: IgA Pemphigus
Chapter 36: Pemphigus Vulgaris
Chapter 37: Pemphigus Vegetans
Chapter 38: Paraneoplastic Pemphigus
Chapter 39: Darier’s Disease (Keratosis Follicularis)
Chapter 40: Hailey-Hailey Disease (Familial Benign Pemphigus)
Chapter 41: Grover’s Disease (Transient Acantholytic Dermatosis)
F: Subepidermal Vesicular Dermatitis
Chapter 42: Bullous Pemphigoid
Chapter 43: Pemphigoid (Herpes) Gestationis
Chapter 44: Mucosal (Cicatricial) Pemphigoid
Chapter 45: Epidermolysis Bullosa Acquisita
Chapter 46: Epidermolysis Bullosa Congenita
Chapter 47: Dermatitis Herpetiformis
Chapter 48: Linear IgA Disease
Chapter 49: Porphyria Cutanea Tarda
Chapter 50: Pseudoporphyria
G: Granulomatous Dermatitis
Chapter 51: Granuloma Annulare
Chapter 52: Necrobiosis Lipoidica
Chapter 53: Rheumatoid Nodule
Chapter 54: Palisaded Neutrophilic and Granulomatous Dermatitis
Chapter 55: Necrobiotic Xanthogranuloma
Chapter 56: Sarcoidosis
Chapter 57: Cutaneous Crohn’s Disease
Chapter 58: Foreign-Body Granulomata
H: Superficial and Deep Perivascular Dermatitis
Chapter 59: Erythema Annulare Centrifugum
Chapter 60: Urticaria
Chapter 61: Polymorphous Light Eruption
I: Folliculitis, Perifolliculitis, and Inflammation of the Sweat Apparatus
Chapter 62: Acne Vulgaris
Chapter 63: Rosacea
Chapter 64: Hidradenitis Suppurativa
Chapter 65: Acne Agminata
Chapter 66: Folliculitis
Chapter 67: Eosinophilic Folliculitis
Chapter 68: Neutrophilic Eccrine Hidradenitis
Chapter 69: Acne Keloidalis Nuchae
J: Alopecia
Chapter 70: Alopecia Areata
Chapter 71: Androgenetic Alopecia
Chapter 72: Dissecting Cellulitis (Dissecting Folliculitis)
Chapter 73: Follicular Degeneration Syndrome
Chapter 74: Folliculitis Decalvans
Chapter 75: Lichen Planopilaris (LPP) and Frontal Fibrosing Alopecia
K: Vasculitis and Vasculopathy
Chapter 76: Leukocytoclastic Vasculitis (LCV)
Chapter 77: Henoch-Schönlein Purpura (HSP)
Chapter 78: Urticarial Vasculitis
Chapter 79: Granuloma Faciale
Chapter 80: Erythema Elevatum Diutinum
Chapter 81: Polyarteritis Nodosa
Chapter 82: Wegener’s Granulomatosis
Chapter 83: Churg-Strauss Syndrome (Allergic Granulomatosis with Angiitis)
Chapter 84: Disseminated Intravascular Coagulopathy (DIC)
Chapter 85: Cryoglobulinemia
Chapter 86: Antiphospholipid Antibody Syndrome
Chapter 87: Coumadin (Warfarin) Necrosis
Chapter 88: Cholesterol Crystal Embolism
Chapter 89: Giant Cell (Temporal) Arteritis
Chapter 90: Atrophie Blanche (Livedoid Vasculitis)
Chapter 91: Lymphocytic Vasculitis
Chapter 92: Perniosis
Chapter 93: Degos’ Disease (Malignant Atrophic Papulosis)
Chapter 94: Pigmented Purpura
L: Fibrosing/Sclerosing Dermatitis
Chapter 95: Morphea
Chapter 96: Scleroderma (Systemic Sclerosis)
Chapter 97: Lichen Sclerosus
Chapter 98: Nephrogenic Systemic Fibrosis
Chapter 99: Radiation Dermatitis
M: Panniculitis
Chapter 100: Erythema Nodosum
Chapter 101: α Antitrypsin Deficiency–Associated Panniculitis
Chapter 102: Pancreatic Panniculitis
Chapter 103: Subcutaneous Fat Necrosis of the Newborn
Chapter 104: Nodular Vasculitis/Erythema Induratum
Chapter 105: Lupus Profundus
Chapter 106: Factitial and Traumatic Fat Necrosis
Chapter 107: Lipodermatosclerosis (Sclerosing Panniculitis)
Chapter 108: Infective Panniculitis
N: Other Inflammatory Dermatoses
Chapter 109: Sweet’s Syndrome (Acute Febrile Neutrophilic Dermatosis)
Chapter 110: Pyoderma Gangrenosum
Chapter 111: Behçet’s Disease
Chapter 112: Eosinophilic Cellulitis (Wells’ Syndrome)
Chapter 113: Eosinophilic Fasciitis (Schulman’s Syndrome)
Chapter 114: Zoon’s Balanitis
O: Disorders of Keratinization
Chapter 115: Ichthyosis Vulgaris
Chapter 116: X-Linked Recessive Ichthyosis
Chapter 117: Lamellar Ichthyosis
Chapter 118: Congenital Bullous Ichthyosiform Erythroderma
Chapter 119: Palmoplantar Keratoderma (PPK)
Chapter 120: Porokeratosis
Chapter 121: Axillary Granular Parakeratosis
II: Infectious Dermatitis
A: Viral Infections
Chapter 122: Verruca Vulgaris
Chapter 123: Verruca Plantaris (Plantar Wart)
Chapter 124: Verruca Plana (Plane Wart)
Chapter 125: Condyloma Acuminatum
Chapter 126: Molluscum Contagiosum
Chapter 127: Herpes Simplex
Chapter 128: Varicella-Zoster Virus (VZV)
Chapter 129: ORF (Ecthyma Contagiosum)
B: Bacterial Infections
Chapter 130: Impetigo
Chapter 131: Staphylococcal–Scalded Skin Syndrome
Chapter 132: Necrotizing Fasciitis
Chapter 133: Ecthyma
Chapter 134: Bacillary Angiomatosis
Chapter 135: Actinomycosis
Chapter 136: Granuloma Inguinale
Chapter 137: Anthrax
Chapter 138: Corynebacterial Infections
Chapter 139: Lyme Disease
Chapter 140: Syphilis
Chapter 141: Lupus Vulgaris
Chapter 142: Atypical Mycobacterial Infections
Chapter 143: Leprosy
C: Fungal Infections
Chapter 144: Dermatophytosis
Chapter 145: Tinea Versicolor
Chapter 146: Candida
Chapter 147: Pityrosporum Folliculitis
Chapter 148: Mycetoma
Chapter 149: North American Blastomycosis
Chapter 150: Histoplasmosis
Chapter 151: Cryptococcosis
Chapter 152: Coccidioidomycosis
Chapter 153: Paracoccidioidomycosis (South American Blastomycosis)
Chapter 154: Chromoblastomycosis (Chromomycosis)
Chapter 155: Phaeohyphomycosis
Chapter 156: Sporotrichosis
Chapter 157: Aspergillosis
Chapter 158: Zygomycosis
D: Other Infections
Chapter 159: Protothecosis
Chapter 160: Rhinosporidiosis
Chapter 161: Leishmaniasis
Chapter 162: Amoebiasis Cutis
Chapter 163: Onchocerciasis
Chapter 164: Schistosomiasis (Bilharzia)
Chapter 165: Scabies
Chapter 166: Tungiasis
III: Noninflammatory Dermatoses
A: Metabolic and Degenerative Disorders
Chapter 167: Necrolytic Migratory Erythema
Chapter 168: Acrodermatitis Enteropathica
Chapter 169: Cutaneous Amyloidosis
Chapter 170: Adult Colloid Milium
Chapter 171: Juvenile Colloid Milium
Chapter 172: Gout
Chapter 173: Lichen Myxedematosus/Scleromyxedema
Chapter 174: Scleredema (Buschke)
Chapter 175: Pretibial Myxedema
Chapter 176: Follicular Mucinosis
Chapter 177: Calcinosis Cutis
Chapter 178: Calciphylaxis
Chapter 179: Chondrodermatitis Nodularis Helicis
B: Diseases of Collagen and Elastic Tissue
Chapter 180: Pseudoxanthoma Elasticum
Chapter 181: Elastosis Perforans Serpiginosa
Chapter 182: Reactive Perforating Collagenosis
Chapter 183: Kyrle’s Disease (Hyperkeratosis Follicularis et Parafollicularis in Cutem Penetrans)
C: Disorders of Pigmentation
Chapter 184: Vitiligo
Chapter 185: Drug-Induced Pigmentation
IV: Neoplasms
A: Cysts and Pseudocysts
Chapter 186: Dilated Pore of Winer
Chapter 187: Epidermoid (Infundibular) Cyst
Chapter 188: Pilar (Trichilemmal) Cyst
Chapter 189: Proliferating Pilar Tumor
Chapter 190: Steatocystoma
Chapter 191: Eruptive Vellus Hair Cyst
Chapter 192: Hidrocystoma
Chapter 193: Cutaneous Ciliated Cyst
Chapter 194: Dermoid Cyst
Chapter 195: Digital Myxoid (Mucous) Cyst
B: Melanocytic Neoplasms
Chapter 196: Ephelis
Chapter 197: Lentigo
Chapter 198: Ink Spot Lentigo
Chapter 199: Labial Melanotic Macule
Chapter 200: Melanocytic Nevus
Chapter 201: Acral Nevus
Chapter 202: Congenital Melanocytic Nevus
Chapter 203: Halo Nevus (Sutton’s Nevus)
Chapter 204: Balloon Cell Nevus
Chapter 205: Recurrent (Persistent) Nevus (Pseudomelanoma)
Chapter 206: Atypical Genital (Milk-Line, Flexural) Nevus (Nevus of Special Anatomic Sites)
Chapter 207: Dysplastic Nevus
Chapter 208: Spitz Nevus
Chapter 209: Pigmented Spindle Cell Nevus (Reed Nevus)
Chapter 210: Nevus of Ota (Nevus Fusoceruleus Ophthalmomaxillaris) and Nevus of Ito (Nevus Fusoceruleus Acromioclavicularis)
Chapter 211: Blue Nevus
Chapter 212: Combined Nevus
Chapter 213: Deep Penetrating Nevus
Chapter 214: Melanoma
C: Keratinocytic Neoplasms
Chapter 215: Epidermal Nevus
Chapter 216: Seborrheic Keratosis
Chapter 217: Inverted Follicular Keratosis (Irritated Seborrheic Keratosis)
Chapter 218: Stucco Keratosis
Chapter 219: Borst-Jadassohn Phenomenon
Chapter 220: Large Cell Acanthoma
Chapter 221: Acantholytic Acanthoma
Chapter 222: Warty Dyskeratoma
Chapter 223: Clear Cell Acanthoma
Chapter 224: Actinic Keratosis
Chapter 225: Squamous Cell Carcinoma in Situ
Chapter 226: Squamous Cell Carcinoma
Chapter 227: Keratoacanthoma
Chapter 228: Verrucous Carcinoma
Chapter 229: Basal Cell Carcinoma
D: Follicular Neoplasms
Chapter 230: Trichoepithelioma
Chapter 231: Desmoplastic Trichoepithelioma
Chapter 232: Trichilemmoma
Chapter 233: Desmoplastic Trichilemmoma
Chapter 234: Tumor of the Follicular Infundibulum (Infundibuloma)
Chapter 235: Pilar Sheath Acanthoma
Chapter 236: Basaloid Follicular Hamartoma
Chapter 237: Trichoblastoma
Chapter 238: Trichofolliculoma
Chapter 239: Pilomatrixoma
Chapter 240: Lymphadenoma Cutis
Chapter 241: Trichilemmal Carcinoma
Chapter 242: Matrical Carcinoma (Pilomatrix Carcinoma, Malignant Pilomatrixoma)
E: Sebaceous Neoplasms
Chapter 243: Nevus Sebaceus of Jadassohn (Organoid Nevus)
Chapter 244: Sebaceous Hyperplasia
Chapter 245: Sebaceous Adenoma
Chapter 246: Sebaceoma
Chapter 247: Sebaceous Carcinoma
F: Eccrine/Apocrine Neoplasms
Chapter 248: Poroma
Chapter 249: Dermal Duct Tumor
Chapter 250: Eccrine Syringofibroadenoma (Acrosyringeal Nevus)
Chapter 251: Syringoma
Chapter 252: Nodular Hidradenoma
Chapter 253: Chondroid Syringoma (Mixed Tumor)
Chapter 254: Eccrine Spiradenoma
Chapter 255: Cylindroma
Chapter 256: Syringocystadenoma Papilliferum
Chapter 257: Hidradenoma Papilliferum
Chapter 258: Tubular Apocrine Adenoma (Papillary Tubular Adenoma)
Chapter 259: Papillary Eccrine Adenoma
Chapter 260: Microcystic Adnexal Carcinoma
Chapter 261: Adenoid Cystic Carcinoma
Chapter 262: Eccrine Porocarcinoma
Chapter 263: Primary Cutaneous Mucinous Carcinoma
Chapter 264: Hidradenocarcinoma (Malignant Acrospiroma, Clear Cell Hidradenocarcinoma)
Chapter 265: Eccrine Ductal Carcinoma
Chapter 266: Aggressive Digital Papillary Adenocarcinoma
Chapter 267: Apocrine Carcinoma
G: Fibrous, Fibrohistiocytic, and Myofibroblastic Neoplasms
Chapter 268: Hypertrophic Scar
Chapter 269: Keloid
Chapter 270: Fibrous Papule
Chapter 271: Acrochordon (Fibroepithelial Polyp, Skin Tag)
Chapter 272: Acquired Digital Fibrokeratoma
Chapter 273: Superficial Angiomyxoma
Chapter 274: Palmar Fibromatosis (Dupuytren’s Contracture)
Chapter 275: Nodular Fasciitis
Chapter 276: Elastofibroma
Chapter 277: Fibroma of Tendon Sheath
Chapter 278: Giant Cell Tumor of Tendon Sheath
Chapter 279: Inclusion Body Fibromatosis (Infantile Digital Fibromatosis)
Chapter 280: Fibrous Hamartoma of Infancy
Chapter 281: Sclerotic Fibroma (Storiform Collagenoma)
Chapter 282: Infantile Myofibromatosis and Solitary Myofibroma
Chapter 283: Myoepithelioma
Chapter 284: Solitary Fibrous Tumor
Chapter 285: Dermatofibroma (Fibrous Histiocytoma)
Chapter 286: Cellular Fibrous Histiocytoma
Chapter 287: Atypical Fibrous Histiocytoma
Chapter 288: Dermatomyofibroma
Chapter 289: Dermatofibrosarcoma Protuberans (DFSP)
Chapter 290: Giant Cell Fibroblastoma
Chapter 291: Atypical Fibroxanthoma
Chapter 292: Superficial Malignant Fibrous Histiocytoma (Superficial Pleomorphic Sarcoma—NOS)
Chapter 293: Epithelioid Sarcoma
H: Vascular Neoplasms
Chapter 294: Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor)
Chapter 295: Lobular Capillary Hemangioma (Pyogenic Granuloma)
Chapter 296: Port Wine Stain
Chapter 297: Infantile Hemangioma (Strawberry Nevus, Juvenile Hemangioma, Infantile Hemangioendothelioma)
Chapter 298: Cavernous Hemangioma
Chapter 299: Arteriovenous Hemangioma (Arteriovenous Malformation, Cirsoid Aneurysm)
Chapter 300: Cherry Hemangioma (Senile Hemangioma, Campbell de Morgan Spot)
Chapter 301: Angiokeratoma
Chapter 302: Hobnail Hemangioma (Targetoid Hemosiderotic Hemangioma)
Chapter 303: Spindle Cell Hemangioma
Chapter 304: Multinucleate Cell Angiohistiocytoma
Chapter 305: Epithelioid Hemangioma (Angiolymphoid Hyperplasia with Eosinophilia)
Chapter 306: Reactive Angioendotheliomatosis
Chapter 307: Lymphangioma Circumscriptum
Chapter 308: Glomus Tumor/Glomangioma
Chapter 309: Myopericytoma
Chapter 310: Epithelioid Hemangioendothelioma
Chapter 311: Kaposi’s Sarcoma
Chapter 312: Cutaneous Angiosarcoma
Chapter 313: Epithelioid Angiosarcoma
I: Neural-Neuroendocrine Neoplasms
Chapter 314: Traumatic Neuroma
Chapter 315: Morton’s Neuroma (Metatarsalgia)
Chapter 316: Neurofibroma
Chapter 317: Schwannoma (Neurilemmoma)
Chapter 318: Palisaded Encapsulated Neuroma (Solitary Circumscribed Neuroma)
Chapter 319: Granular Cell Tumor
Chapter 320: Neurothekeoma (Myxoid Neurothekeoma, Dermal Nerve Sheath Myxoma)
Chapter 321: Cellular Neurothekeoma
Chapter 322: Perineurioma
Chapter 323: Nasal Glioma
Chapter 324: Malignant Peripheral Nerve Sheath Tumor (Neurofibrosarcoma, Malignant Schwannoma)
Chapter 325: Merkel Cell Carcinoma
J: Muscular Neoplasms
Chapter 326: Leiomyoma and Angioleiomyoma
Chapter 327: Leiomyosarcoma
K: Adipose, Osseous, and Cartilaginous Neoplasms
Chapter 328: Lipoma
Chapter 329: Angiolipoma
Chapter 330: Spindle Cell Lipoma
Chapter 331: Pleomorphic Lipoma
Chapter 332: Liposarcoma
Chapter 333: Osteoma Cutis
Chapter 334: Soft Tissue Chondroma
L: T-Cell (and NK/T-Cell) Neoplasms
Chapter 335: T-Cell Pseudolymphoma
Chapter 336: Chronic Actinic Dermatitis (Actinic Reticuloid)
Chapter 337: Mycosis Fungoides
Chapter 338: Sézary Syndrome
Chapter 339: Pagetoid Reticulosis
Chapter 340: Granulomatous Slack Skin
Chapter 341: Primary Cutaneous Aggressive Epidermotropic CD8-Positive Cytotoxic T-Cell Lymphoma
Chapter 342: Lymphomatoid Papulosis
Chapter 343: Anaplastic Large Cell Lymphoma (ALCL)
Chapter 344: Subcutaneous Panniculitis-Like T-Cell Lymphoma
Chapter 345: Adult T-Cell Leukemia/Lymphoma (ATLL)
Chapter 346: Extranodal NK/T-Cell Lymphoma, Nasal Type
Chapter 347: Gamma/Delta T-Cell Lymphoma
M: B-Cell Neoplasms
Chapter 348: B-Cell Pseudolymphoma (Cutaneous Lymphoid Hyperplasia)
Chapter 349: Primary Cutaneous Marginal Zone B-Cell Lymphoma/Immunocytoma
Chapter 350: Primary Cutaneous Follicle Center Lymphoma (PCFCL)
Chapter 351: Primary Cutaneous Diffuse Large B-Cell Lymphoma
Chapter 352: Intravascular B-Cell Lymphoma
Chapter 353: Lymphomatoid Granulomatosis
N: Xanthomatous, Histiocytic, Mast Cell, Myeloid Neoplasms, and Plasma Cell
Chapter 354: Xanthomata
Chapter 355: Xanthogranuloma (Juvenile)
Chapter 356: Xanthoma Disseminatum
Chapter 357: Verruciform Xanthoma
Chapter 358: Rosai-Dorfman Disease
Chapter 359: Reticulohistiocytoma
Chapter 360: Langerhans Cell Histiocytosis
Chapter 361: Cutaneous Mastocytosis
Chapter 362: Leukemia Cutis
Chapter 363: Plasmacytoma
O: Cutaneous Metastases/Implantation
Chapter 364: Cutaneous Endometriosis
Chapter 365: Cutaneous Metastases
Chapter 366: Extramammary Paget’s Disease
Index
I
Inflammatory Dermatitis
A
Spongiotic Dermatitis
Atopic Dermatitis

Definition

• Eczematous dermatitis in individuals as manifestation of atopic diathesis

Clinical features

Epidemiology

• Affects those with atopic tendency (associated with allergic rhinitis and asthma)
• Familial predisposition
• Typically arises in infancy or childhood; delayed onset in adulthood less common

Presentation

• Eczematous reaction pattern with classically dry, scaly, pruritic patches and plaques
• Often symmetrically distributed
• Infancy: extensor involvement
• Childhood: flexural involvement of arms and legs, trunk, face (with sparing of nose—“headlight sign”)
• With chronicity, lichenification and dyspigmentation occur

Prognosis and treatment

• Lifelong tendency, although many improve over time
• Risk for superinfection (impetiginization or eczema herpeticum)
• Dry skin care important part of management
• Therapeutic regimen includes topical corticosteroids, topical calcineurin-inhibitors, antihistamines, systemic immunosuppressives (e.g., methotrexate, cyclosporine), phototherapy

Pathology

Histology

• Acute: mild acanthosis, epidermal spongiosis, lymphocytic exocytosis, superficial dermal perivascular lymphohistiocytic infiltrate sometimes accompanied by eosinophils
• Subacute: parakeratosis, acanthosis, variable epidermal spongiosis, superficial dermal chronic inflammation
• Chronic: hyperkeratosis, psoriasiform epidermal hyperplasia, hypergranulosis, spongiosis less prominent or absent

Immunopathology (including immunohistochemistry)

• Not contributory

Main differential diagnoses

• Other spongiotic dermatitides including nummular eczema, contact dermatitis
• Seborrheic dermatitis
• Spongiotic drug eruption
• Dermatophytosis

Fig 1 Atopic dermatitis. Pruritic, dry, scaly, ill-defined patches symmetrically distributed in the bilateral antecubital fossae.

Fig 2 Atopic dermatitis. Numerous few-millimeter erythematous eczematous papules, several excoriated, over the left medial thigh.

Fig 3 Atopic dermatitis. Focally crusted, fairly discrete, hyperkeratotic, pink erythematous, nummular plaque in a patient with atopic dermatitis.


Fig 4 Atopic dermatitis. There is hyperkeratosis, parakeratosis, and psoriasiform hyperplasia associated with mild spongiosis in this example of subacute atopic dermatitis.

Fig 5 Atopic dermatitis. Intraepidermal Langerhans cell microgranuloma with surrounding spongiosis.

Fig 6 Atopic dermatitis. Spongiosis and lymphocytic exocytosis.

Fig 7 Atopic dermatitis. In the dermis, there is a lymphocytic infiltrate with an eosinophil and melanophages.

Fig 8 Chronic spongiotic dermatitis. Hyperkeratosis with crusting and acanthosis. Note the superficial perivascular chronic inflammatory cell infiltrate.

Fig 9 Chronic spongiotic dermatitis. There is parakeratosis and focal spongiosis with lymphocytic exocytosis.
Seborrheic Dermatitis

Definition

• Common papulosquamous skin condition affecting sebum-rich areas of the body

Clinical features

Epidemiology

• Predilection for whites
• May arise in infancy but more common in adults, beginning with puberty
• Can be particularly prominent in AIDS patients and patients with neurologic disorders

Presentation

• Greasy, scaling erythema in a seborrheic (sebum-rich) distribution: scalp, eyebrows, perinasal region, beard area, presternal chest, axillae, and groin
• Scalp involvement prompts patient’s complaint of dandruff and pruritus
• In particularly inflammatory areas, erythematous 2- to 4-mm papules sometimes seen
• Affected areas can be pruritic or burning
• Erythroderma rare: occurs in AIDS and patients with neurologic disorders

Prognosis and treatment

• Benign process with waxing-waning course
• Topical steroids or topical calcineurin-inhibitors (e.g., tacrolimus, pimecrolimus) to calm inflammation
• Antiseborrheic shampoos (containing ingredients such as zinc pyrithione, selenium sulfide, tar preparations, keratolytics)
• Topical or, if indicated, oral, ketoconazole, or other antifungals (e.g., other azoles or allylamines)
• Certain medications may flare condition (e.g., lithium, buspirone, chlorpromazine, gold)
• Occasional superinfection can occur

Pathology

Histology

• Features of subacute spongiotic dermatitis: mildly spongiotic epidermis topped by mounded parakeratosis (often perifollicular), lymphocytic exocytosis, mild superficial perivascular infiltrate of lymphocytes, histiocytes, and scattered eosinophils
• Irregular epidermal hyperplasia
• Intracorneal neutrophilic collections (often perifollicular) may be present
• Intracorneal pityrosporum organisms sometimes found

Immunopathology

• Not contributory

Main differential diagnoses

• Other subacute spongiotic conditions
• Psoriasis

Fig 1 Seborrheic dermatitis. Erythema and marked scaling affecting the beard area.

Fig 2 Seborrheic dermatitis. Hyperkeratosis with characteristic perifollicular parakeratosis. A superficial perivascular lymphohistiocytic infiltrate is present.

Fig 3 Seborrheic dermatitis. High-power view showing perifollicular parakeratosis, focal spongiosis, and lymphocytic exocytosis.
Allergic Contact Dermatitis

Definition

• Cutaneous delayed hypersensitivity reaction to exogenous antigen

Clinical features

Epidemiology

• Affects any age, either sex
• Common contactants include nickel, Rhus (uroshiol), fragrance, neomycin/bacitracin, formaldehyde, quaternium-15

Presentation

• Eczematous reaction pattern at areas in contact with the offending antigen, so characteristically linear or in geometric pattern
• Acutely, exposed areas may be weepy, blistering, brightly erythematous edematous papules and plaques, often with excoriation, sometimes with crusting
• With time, areas become xerotic, develop more prominent scale, and may leave postinflammatory hyper/hypopigmentation

Prognosis and treatment

• Classically self-limited over days to weeks after removal of causative agent
• Treatment with topical and systemic corticosteroids
• Immunosuppressive treatment may blunt histologic features
• Secondary impetiginization can occur, may require treatment with topical/oral antibiotics

Pathology

Histology

• Acute : prominent epidermal spongiosis often with vesiculation, lymphocytic exocytosis, conspicuous epidermal Langerhans cells, may form microabscesses, superficial dermal perivascular lymphohistiocytic infiltrate with eosinophils, papillary dermal edema
• Subacute : focal parakeratosis, epidermal spongiosis less conspicuous, mild epidermal hyperplasia, superficial dermal chronic inflammation
• Chronic : focal parakeratosis, psoriasiform epidermal hyperplasia, spongiosis much less prominent or absent, papillary dermal fibrosis

Immunopathology (including immunohistochemistry)

• Not contributory

Main differential diagnoses

• Other spongiotic dermatitides (e.g., seborrheic dermatitis, spongiotic drug eruption)
• Insect bite reaction
• Sézary syndrome
• Mycosis fungoides may resemble the subacute and chronic forms of dermatitis

Fig 1 Allergic contact dermatitis. Florid example of an acute lesion showing diffuse vesiculation.

Fig 2 Allergic contact dermatitis. Eczematous scaly erythematous plaque on the chest with sharp demarcation at the inferior border, representing allergic contact dermatitis to perfume.

Fig 3 Allergic contact dermatitis. Fairly well-demarcated plaque formed by a coalescence of erythematous few-millimeter papules, with areas of focally crusted erosion in the infraumbilical area as a result of nickel allergy in a belt buckle.


Fig 4 Allergic contact dermatitis. Crusting, psoriasiform hyperplasia, and spongiosis with vesiculation.

Fig 5 Allergic contact dermatitis. Spongiosis and marked lymphocytic exocytosis.

Fig 6 Allergic contact dermatitis. Dermal edema with a superficial perivascular lymphohistiocytic infiltrate. Note the eosinophils.

Fig 7 Allergic contact dermatitis. Conspicuous Langerhans cells.

Fig 8 Allergic contact dermatitis. Chronic lesion showing hyperkeratosis, focal mild parakeratosis, psoriasiform hyperplasia, and fibrosis of the papillary dermis.
Dyshidrotic Eczema (Pompholyx)

Definition

• Recurrent vesicular dermatitis of the hands and feet

Clinical features

Epidemiology

• Most commonly presents in adults in the third to fifth decades of life, but children, teens, and elderly also affected
• More often seen in females
• No clear racial predilection

Presentation

• Pruritic eruption of 1- to 2-mm deep-seated, tapioca pudding–like vesicles embedded in the palms, along the finger sides, and soles
• Background variable scaling erythema
• Hyperhidrosis may be seen
• Typically lasts 2 to 4 weeks, but, not uncommonly, can experience recurrent episodes
• Longitudinal furrowing of nails sometimes occurs

Prognosis and treatment

• Topical (or intralesional or systemic) corticosteroids, topical calcineurin inhibitors, PUVA (topical soaks or with hand/foot unit) form the mainstay of therapy
• Botulinum toxin now being offered

Pathology

Histology

• Epidermal spongiosis with intraepidermal spongiotic macrovesiculation
• Superficial perivascular lymphocytic inflammation
• Occasional eosinophils

Special stains/immunopathology

• Not contributory

Main differential diagnoses

• Dermatophyte infection
• Acute contact dermatitis

Fig 1 Dyshidrotic eczema. Erythematous papulovesicles on the palm.

Fig 2 Dyshidrotic eczema. Scanning view showing multiple large intraepidermal vesicles.

Fig 3 Dyshidrotic eczema. High-power view showing spongiotic vesicle. In view of the conspicuous neutrophils, a secondary infection should be excluded.
Stasis Dermatitis

Definition

• Eczematous changes, classically of the lower legs—attributed to venous stasis (varicose veins)

Clinical features

Epidemiology

• Older individuals (generally after fifth decade of life)
• Patients with venous insufficiency (e.g., parous women, patients with chronic congestive heart failure, patient status—posttrauma or surgery to a lower extremity)

Presentation

• Pruritic and sometimes painful, occasionally weeping, scaling erythema of the lower legs, often beginning just proximal to the ankles
• Underlying lower extremity edema
• With time, skin assumes violaceous-brown hue related to hemosiderin deposition
• Can become lichenified and acquire very thick retention hyperkeratosis
• Impetiginization with honey-colored crusting or other secondary infection frequent
• Ulceration often occurs, particularly over the medial malleolus
• Advanced stasis changes can give rise to ill-defined, dome-shaped, thick erythematous to violaceous papules that can resemble vascular tumors (acroangiodermatitis)
• Atrophie blanche, with porcelain white scarring studded by pinpoint red vascular macules seen in advanced cases
• Ulcerated chronic lesions may develop nonmelanoma skin cancer

Prognosis and treatment

• Slowly progressive course, can result in secondary infection, ulceration, and/or lipodermatosclerosis
• Topical corticosteroids or calcineurin inhibitors to relieve inflammation
• Measures to counter effects of gravity and provide compression (e.g., leg elevation, support hose) can help slow progression
• Antiplatelet agents (e.g., aspirin, pentoxifylline)
• For stasis ulcers, Unna boots, porcine grafting, and, sometimes, hyperbaric oxygen used
• Antibiotics as indicated for cases of superinfection
• Beware allergic contact dermatitis from topical medication

Pathology

Histology

• Variable hyperkeratosis and acanthosis with serous crust
• Epidermal spongiosis overlying superficial perivascular chronic inflammatory cell infiltrate
• Conspicuous superficial dermal lobular vascular proliferation
• Fibrin deposition
• Dermal fibrosis with hemosiderin deposition

Immunopathology

• Not contributory

Main differential diagnosis

• Nummular or atopic dermatitis

Fig 1 Stasis dermatitis. Lower leg showing scaling erythema with overlying mammillated plaques and background pitting edema.

Fig 2 Stasis dermatitis. Ill-defined erythema with relative loss of hair on the lower extremity.


Fig 3 Stasis dermatitis. Low-power view showing hyperkeratosis, an irregular epidermis, and a superficial inflammatory cell infiltrate.

Fig 4 Stasis dermatitis. High-power view showing blood vessel wall fibrin deposition. The features of stasis dermatitis often overlap with atrophie blanche.

Fig 5 Stasis dermatitis. Dermal fibrosis as shown in this field is generally present.

Fig 6 Stasis dermatitis. Note the vascular proliferation.

Fig 7 Stasis dermatitis. Red cell extravasation is conspicuous.

Fig 8 Stasis dermatitis. This field shows blood vessel wall hyalinization and hemosiderin deposits.
Spongiotic Drug Eruption

Definition

• Eczematous cutaneous hypersensitivity reaction to a drug

Clinical features

Epidemiology

• Adults and children affected
• Common drugs implicated include antibiotics (e.g., penicillins), sulfa-based medications, ethylenediamine
• Can be initiated by topical contact sensitization

Presentation

• Eruption arises upon initial exposure to drug or upon reexposure to medication to which individual had been previously sensitized
• May be preceded by generalized pruritus
• Diffuse, usually symmetric eczematous, scaling erythematous thin plaques
• Areas of crusted erosions and microvesiculation may be seen
• Dyshidrotic vesicles on palms occur in some cases
• In generalized cases, may mimic erythrodermic atopic dermatitis

Prognosis and treatment

• Discontinuation of culprit medication
• Symptomatic, supportive care (e.g., topical corticosteroids, antihistamines)

Pathology

Histology

• Focal parakeratosis, variable acanthosis
• Lymphocyte exocytosis with spongiosis
• Intraepidermal microvesiculation
• Eosinophilic spongiosis occasionally seen
• Cytoid bodies often present
• Superficial perivascular predominantly lymphocytic inflammation with scattered eosinophils

Special stains/immunopathology

• Not contributory

Main differential diagnoses

• Dermatophyte infection
• Other causes of spongiotic dermatitis (e.g., atopic dermatitis, allergic contact dermatitis, seborrheic dermatitis)
• Mycosis fungoides

Fig 1 Spongiotic drug eruption. Eczematous scaly erythema of the face thought to be secondary to antihypertensive medication.

Fig 2 Spongiotic drug eruption. There is hyperkeratosis, acanthosis, and mild spongiosis. A heavy perivascular infiltrate is seen in the superficial dermis.

Fig 3 Spongiotic drug eruption. Note the spongiosis and the presence of eosinophils.
Arthropod Bite Reaction

Definition

• Clinicopathologic constellation of findings due to an arthropod bite

Clinical features

Epidemiology

• Quite common
• Wide age range
• Secondary to any arthropod including fleas, mosquitoes, bed bugs, mites, ticks, spiders, bees, wasps

Presentation

• Solitary or multiple lesions
• Urticarial papules, vesicles, or plaques are possible
• Pruritus
• Punctum may be clinically evident
• Wide anatomic distribution, but some areas (e.g., face and legs) are more common
• Source of arthropod may not be clear
• Necrosis in cases of tick bites and spider bites

Prognosis and treatment

• Symptomatic treatment: topical corticosteroids, antihistamines, epinephrine if severe type I hypersensitivity reaction develops
• Secondary bacterial infection possible
• Some lesions may persist for months, particularly with tick bites and retained parts
• Anaphylaxis may occur in those who are hypersensitive

Pathology

Histology

• Epidermal necrosis or ulceration
• Variable degree of spongiosis with or without intraepidermal eosinophils
• Subepidermal edema may be evident and can be very marked in severe reactions
• Wedge-shaped infiltrate of neutrophils, lymphocytes, and eosinophils
• Flame figures sometimes seen
• Infiltrate is perivascular (superficial and deep) and interstitial
• Thrombi may be seen in spider bites (brown recluse spider)
• Arthropod mouth parts (e.g., tick) can be seen
• Chronic arthropod bite reactions sometimes show cutaneous lymphoid hyperplasia, top-heavy infiltrate, and lymphoid follicles with or without germinal centers (cutaneous B-cell pseudolymphoma, lymphocytoma cutis)
• Eosinophils, plasma cells, giant cells, and granulomata are occasionally seen

Immunopathology/special stains

• CD20 B cells admixed with CD3 T cells in chronic lesions
• Numerous CD30-positive cells may be present
• No evidence of a clonal population in chronic pseudolymphomatous lesions

Main differential diagnoses

• Lymphomatoid papulosis
• Drug reaction
• Lymphoma

Fig 1 Arthropod bite reaction. Clustered erythematous, edematous papules with central vesicles.

Fig 2 Arthropod bite reaction. This example shows ulceration overlying a zone of dermal necrosis with retained arthropod parts.

Fig 3 Arthropod bite reaction. Bullous lesion characterized by massive subepidermal edema.


Fig 4 Arthropod bite reaction. There is a perivascular infiltrate consisting of lymphocytes and conspicuous eosinophils.

Fig 5 Arthropod bite reaction. There is a flame figure in the center of the field.

Fig 6 Arthropod bite reaction. Low-power view of a chronic lesion showing a pseudolymphomatous infiltrate. A follicular architecture is evident.

Fig 7 Arthropod bite reaction. High-power view of a follicle showing mitotic activity and tingible body macrophages.

Fig 8 Arthropod bite reaction. The interfollicular infiltrate consists of lymphocytes, histiocytes, and conspicuous plasma cells.
Incontinentia Pigmenti (Bloch-Sulzberger Syndrome)

Definition

• Genodermatosis characterized by progressive cutaneous blistering, warty papules, and dyspigmentation in a blaschkoid arrangement, caused by mutation in the NEMO gene

Clinical features

Epidemiology

• X-linked dominant; nearly exclusively in females
• Predilection for whites
• Usually noticed at birth
• Majority of cases sporadic, ¼ with family history in mother

Presentation

• Four stages:
Vesicular : plaques studded with vesicles, bullae, and pustules in blaschkoid arrangement, noted at birth; may be extensive, generally distributed to involve the entire body; may recur during febrile episodes
Verrucous : warty, hyperkeratotic plaques replace blistering areas arising at approximately 2 weeks of life
Hyperpigmented : tan-brown hyperpigmented, variably whorled streaks (Chinese lettering) occur along affected Blaschko lines as verrucous stage subsides at approximately a few months of age
Hypopigmented : lighter, cream-colored streaks develop, supplanting and intermixing with hyperpigmented areas during infancy or childhood
• Nail, hair, dental, retinal, and ocular involvement common
• Abnormality of the CNS can cause microcephaly, mental retardation, and seizures

Prognosis and treatment

• Ophthalmologic, CNS complications can be severe
• Skin lesions may become superinfected

Pathology

Histology

• Blistering stage : eosinophilic spongiosis with vacuolar degeneration, prominent dyskeratosis, superficial perivascular eosinophil infiltrate
• Verrucous stage : verruciform epidermal hyperplasia with orthohyperkeratosis, dyskeratosis, scattered eosinophils
• Hyperpigmented stage : superficial dermal pigment incontinence with melanophages and overlying interface changes
• Hypopigmented stage : pigment incontinence with absence of skin appendages

Immunopathology

• Generally not contributory (although negative direct immunofluorescence can exclude primary immunobullous disorder)

Main differential diagnoses

• Blistering stage : infantile bullous pemphigoid, pemphigus vulgaris, erythema toxicum neonatorum, drug hypersensitivity reaction, insect bite reaction
• Verrucous stage : epidermal nevus
• Hyperpigmented stage : postinflammatory hyperpigmentation
• Hypopigmented stage : postinflammatory hypopigmentation, hypomelanosis of Ito

Fig 1 Incontinentia pigmenti. Erythematous, edematous papules and plaques in a linear distribution on the leg of a newborn. Note the scale-crust and vesicles.

Fig 2 Incontinentia pigmenti. Hyperpigmented macules with scale in a linear, whorled pattern on the leg.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 3 Incontinentia pigmenti. Linear hyperpigmented whorled patches on the lower extremity.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 4 Incontinentia pigmenti. Characteristic conical teeth.

Fig 5 Incontinentia pigmenti. Focal eosinophilic spongiosis is present and characteristic of the vesicular phase.

Fig 6 Incontinentia pigmenti. This field shows massive hyperkeratosis, verruciform epidermal hyperplasia, and dyskeratosis
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)
Pityriasis Rosea

Definition

• Generally self-limited cutaneous condition possibly associated with human herpesviruses (HHV-7 and possibly HHV-6) characterized by finely scaling erythematous plaques distributed in classic “Christmas tree” pattern over trunk

Clinical features

Epidemiology

• Young adults
• No gender or racial predilection
• Seasonal: spring and autumn

Presentation

• Initial erythematous scaly lesion (herald patch)
• Followed within approximately 2 weeks by fine, scaly pink erythematous papules and plaques
• Lesions have a characteristic collarette of scale
• Arranged in a “Christmas tree” pattern along skin tension lines
• Distributed over trunk, occasionally proximal extremities
• Variably pruritic
• Atypical variants involving face and neck and distal extremities

Prognosis and treatment

• Self-limited over weeks to months
• Rarely recurs
• Treatment supportive:
• Topical corticosteroids and oral antihistamines may help alleviate pruritus
• Erythromycin and phototherapy efficacy reported

Pathology

Histology

• Variable acanthosis (sometimes psoriasiform)
• Focal hyperkeratosis
• Angulated parakeratosis (tipping scale, so-called tea-pot lid sign)
• Superficial perivascular chronic inflammatory cell infiltrate
• Mild spongiosis, lymphocyte exocytosis
• Intraepidermal and perivascular erythrocytes

Immunopathology (including immunohistochemistry)

• Not contributory

Main differential diagnoses

• Guttate psoriasis
• Other subacute spongiotic dermatitides
• Adverse drug reaction
• Dermatophyte infection
• Erythema annulare centrifugum

Fig 1 Pityriasis rosea. Herald “patch” on the trunk presenting as a discrete, few-centimeter, oval erythematous plaque with collarette of scale.

Fig 2 Pityriasis rosea. Erythematous, oval thin papules with collarette of scale in a “Christmas tree” distribution on the trunk.


Fig 3 Pityriasis rosea. Tiny foci of parakeratosis. The epidermis is acanthotic, and mild spongiosis is evident.

Fig 4 Pityriasis rosea. Note the spongiosis and focal lymphocytic exocytosis. There is a superficial perivascular lymphocytic infiltrate dermal edema and erythrocyte extravasation.

Fig 5 Pityriasis rosea. Sometimes the features are subtle. There is a tiny central focus of parakeratosis and mild acanthosis.

Fig 6 Pityriasis rosea. In this higher-power view, the mound of parakeratosis is evident.

Fig 7 Pityriasis rosea. There is mild spongiosis.
Photosensitive (Phototoxic/Photoallergic) Dermatitis

Definition

• Group of conditions that are induced and/or exacerbated by UV light

Clinical features

Epidemiology

• While broadly defined, photosensitivity may occur in the setting of polymorphous light eruption, connective tissue diseases (lupus erythematosus), chronic actinic dermatitis (including actinic reticuloid), and the porphyrias
• Phototoxic disorders:
• Not immunologically mediated
• May affect all individuals if the concentration of phototoxic substance is adequate
• Common phototoxic agents: tar, tetracyclines, phenothiazines, psoralens, NSAIDs, griseofulvin
• Phytophotodermatitis:
• Increased photosensitivity caused by plant-related substances
• Common causes: citrus fruits (e.g., lime oil), figs, parsnip, celery
• Photoallergic disorders:
• Affect only sensitive individuals whose immune systems are predisposed to reaction via delayed-type hypersensitivity
• Common photoallergic agents: sunscreens, PABA, fragrances, chlorpromazine, chlorhexidine
• More common at younger ages, with decrease in incidence past middle age

Presentation

• Phototoxic dermatitis:
• Cutaneous flare can begin within minutes of sun exposure
• Tender macular erythema and edema resembling sunburn
• Blistering in severe cases
• Photoallergic dermatitis:
• Reaction occurs to agents to which the individual has been previously sensitized and manifests typically similar to allergic contact dermatitis: pruritic and/or tender, erythema, edema, vesiculation, and weeping that evolves into eczematous morphology with scaling papules and plaques
• Develops lichenification over time
• Postinflammatory dyspigmentation seen
• Lesions located in photosensitive distribution: face, anterior neck, lateral arms, upper back, exposed areas of legs and dorsal feet, with sparing of the submental and infranasal regions

Prognosis and treatment

• Usually self-limited, but recurrent with repeat sun exposure
• Photopatch testing can help elucidate/confirm etiologies for photoallergic cases
• Key to prevention is sun protection, including covering clothing and hat, avoidance of peak hours of sunlight, and appropriate use of sunscreen of adequate SPF
• Acute cases may be treated with topical corticosteroids, antihistamines

Pathology

Histology

• Phototoxic disorders:
• Variable hyperkeratosis
• Variable spongiosis, with occasional intraepidermal or subepidermal vesiculation
• Scattered dyskeratotic cells (sunburn cells)
• Epidermal necrosis in severe cases
• Upper dermal inflammatory cell infiltrate of lymphocytes, histiocytes, and eosinophils
• Melanophages may be present
• Photoallergic disorders:
• Variable acanthosis, parakeratosis, and spongiosis, sometimes with vesiculation
• Superficial perivascular lymphocytic infiltrate with few eosinophils, and scattered melanophages

Immunopathology

• Not contributory

Main differential diagnoses

• Phototoxic disorders histologically may resemble chemotherapy-induced skin changes
• Photoallergic disorders histologically resemble allergic contact dermatitis

Fig 1 Phototoxic dermatitis. Erythema on the dorsal hand with vesicle formation and photo-induced onycholysis.


Fig 2 Photoallergic dermatitis. Erythematous, edematous papules on the upper arm in a photodistribution after sun exposure.

Fig 3 Phototoxic dermatitis. Numerous superficial sunburn cells are present.

Fig 4 Phototoxic dermatitis. High-power view showing apoptosis, keratinocyte vacuolation, and mild spongiosis.

Fig 5 Phototoxic dermatitis. Apoptosis and necrosis of the lower epidermis with subepidermal vesiculation.
(Courtesy of A Lazar, MD, PhD; MD Anderson Cancer Center, Houston.)

Fig 6 Photoallergic dermatitis. Parakeratosis, acanthosis, and an upper dermal perivascular chronic inflammatory cell infiltrate with vascular ectasia. There is no appreciable spongiosis.
(Courtesy of B Swick, MD; University of Iowa, Iowa City.)

Fig 7 Photoallergic dermatitis. High-power view showing a perivascular lymphohistiocytic infiltrate with eosinophils and one or two melanophages.
(Courtesy of B Swick, MD; University of Iowa, Iowa City.)
B
Psoriasiform and Pustular Dermatitis
Psoriasis

Definition

• Cutaneous condition of erythematous, squamous lesions manifesting characteristic histology

Clinical features

Epidemiology

• Familial predisposition supported by twin studies
• Predilection for whites, fair-skin
• Equal gender
• Usually manifests in childhood
• Guttate psoriasis: antecedent strep throat
• Pustular psoriasis: may arise following systemic corticosteroid administration
• Recent research suggesting association with body habitus, nutrition, smoking, alcohol consumption
• Certain drugs (e.g., beta-blockers, lithium) known to exacerbate condition
• AIDS associated with more severe disease

Presentation

• Psoriasis vulgaris characterized by discrete, well-circumscribed erythematous plaques with silvery scale
• Classically located on elbows, knees, scalp, sacrum, umbilicus, buttocks, perianal area
• Generally symmetrically distributed
• Koebner phenomenon: development of psoriatic plaques at sites of trauma
• Auspitz sign: pinpoint bleeding at sites where the overlying scale has been peeled back
• Nail involvement manifesting as pits, oil-drops, onycholysis, nail plate thickening
• Several variants of psoriasis recognized:
• Guttate psoriasis : sudden appearance of drop-like lesions on the trunk and extremities following streptococcal infection
• Inverse psoriasis: lesions develop in skin folds (axilla, perineum/groin)
• Pustular psoriasis (von Zumbusch) : generalized superficial small (1- to 3-mm) pustules, arising on background erythema, sometimes accompanied by fever, calcium abnormalities
• Palmoplantar pustulosis : numerous 1- to 3-mm pustules arising on erythematous palms and soles
• Acrodermatitis continua of Hallopeau : arising in childhood with disseminated pustules
• Erythrodermic psoriasis : generalized erythema usually with diffuse scaling (exfoliative erythroderma)
• Patients with AIDS may have extensive erythroderma, higher incidence of inverse and palmoplantar psoriasis
• Up to 15% of patients with psoriasis can also develop psoriatic arthritis

Prognosis and treatment

• Chronic, lifelong condition with waxing-waning course punctuated by flares and remissions
• Guttate psoriasis self-limited, following appropriate antibiotic treatment for inciting streptococcal infection
• Pustular, erythrodermic psoriasis patients can be systemically ill
• Psoriasis in AIDS patients may be more difficult to treat
• Psoriatic arthritis should be appropriately managed
• Recent studies suggest association between psoriasis and obesity and cardiovascular risk
• Topical therapeutic options include topical corticosteroids; topical coal tar; topical anthralin
• Phototherapeutic options include UVB (narrowband or broadband), PUVA, Excimer laser; chronic PUVA use associated with increased risk for skin cancer
• Systemic therapeutic options include methotrexate; cyclosporine; mycophenolate mofetil; retinoids (acitretin); biologic agents (e.g., etanercept, infiliximab)

Pathology

Histology

• Confluent parakeratosis and hypogranulosis
• Psoriasiform hyperplasia: epidermal acanthosis marked by evenly elongated rete ridges with suprapapillary plate thinning
• Munro microabscesses: intracorneal neutrophilic collections
• Spongiform pustule of Kogoj: spongiotic intraepidermal vesicle with neutrophils
• Epidermis with scattered mitotic figures toward the basilar aspect
• Dilated and tortuous vessels within the papillary dermis
• Mild superficial perivascular lymphocytic infiltrate
• In guttate lesions, characteristic separate small mounds of parakeratosis
• Pustular lesions characterized by large spongiform pustules (macropustule)

Immunopathology

• Not contributory

Main differential diagnoses

• Pityriasis rubra pilaris
• Seborrhoeic dermatitis
• Lichen simplex chronicus
• Inflammatory linear verrucous epidermal nevus
• Psoriasiform drug reaction
• Reiter’s syndrome (pustular variants)


Fig 1 Psoriasis vulgaris. Thin erythematous plaques of psoriasis distributed over the buttocks, a site commonly involved.

Fig 2 Psoriasis vulgaris. Close-up of a psoriatic plaque with prominent micaceous (silver/gray) scale.

Fig 3 Inverse psoriasis. Thin erythematous plaques with slight scale in the axilla.

Fig 4 Psoriasis. Pitting of the nail plate in a patient with generalized, severe psoriasis vulgaris.

Fig 5 Psoriasis vulgaris. Scanning view showing parakeratotic scale and acanthosis with uniform elongation of the rete ridges. Note the ridge fusion on the right side of the field, a common feature.

Fig 6 Psoriasis vulgaris. High-power view showing neutrophils in the parakeratotic stratum corneum. It is always prudent to exclude a fungal infection in a specimen with features such as these.

Fig 7 Psoriasis vulgaris. A typical spongiform pustule, characteristic of psoriasis.

Fig 8 Guttate psoriasis. Note the small parakeratotic mounds typical of this variant.
(From McKee PH, Calonje E, Granter SR: Pathology of the skin, ed 3, London, 2005, Mosby.)

Fig 9 Pustular psoriasis. There is typical psoriasiform hyperplasia surmounted by a macropustule.

Fig 10 Pustular psoriasis. High-power view showing extensive spongiform pustulation.

Fig 11 Pustular psoriasis. In this example, the adjacent epidermis shows psoriasiform hyperplasia although there is no evidence of parakeratosis.

Fig 12 Pustular psoriasis. There is gross dilatation of the superficial dermal vasculature.
Reiter’s Syndrome

Definition

• Multiorgan autoimmune syndrome characterized by orogenital ulcers, arthritis, conjunctivitis, and psoriasiform skin lesions

Clinical features

Epidemiology

• Affects young adults
• Cases triggered by venereal infection, much more commonly males; postenteric infectious cases show an equal gender incidence
• HLA-B27 risk factor
• Associated with HIV disease

Presentation

• Infection typically of the gastrointestinal (e.g., Shigella ; also Salmonella , Yersinia ) or genitourinary (e.g., Chlamydia ) systems precipitates syndrome several days to few weeks later
• Constitutional symptoms may be present
• Classic triad of arthritis, nongonococcal urethritis, and conjunctivitis
• Prostate and bladder may also be affected
• Typically arthritis of lower extremities, can have dactylitis (sausage digit), sacroiliitis, ankylosing spondylitis
• Conjunctivitis with discharge, iritis
• “Balanitis circinata”: sharply circumscribed, shallow, painless genital ulceration located on glans penis in uncircumcised men; keratotic papules in circumcised men; subsequent crusting, scarring, and pain may develop; “vulvitis circinata” in women
• Associated erythema of urethral meatus, or vulvovaginitis
• “Keratoderma blennorrhagicum”: erythematous vesiculopustules evolve into hyperkeratotic papules and plaques, nodules, commonly on acral surfaces (palms, soles, penis, scalp), but also on trunk
• Onychodystrophy with nail thickening, ridging, pitting, onycholysis
• Oral ulcers usually painless

Prognosis and treatment

• Syndrome typically remits after several months, although arthritis may become recurrent or chronic
• Uncommon cases of cardiac complications (e.g., aortic regurgitation), systemic amyloidosis, IgA nephropathy
• Need to treat associated infection adequately with antibiotics
• Topical corticosteroids used for dermatologic findings
• For reactive arthritis, NSAIDs, sulfasalazine commonly used
• Immunosuppressive or biologic agents reserved for severe disease

Pathology

Histology

• Keratoderma blenorrhagicum: parakeratosis, intracorneal macropustules, psoriasiform hyperplasia, spongiosis, intraepidermal neutrophils, superficial dermal chronic inflammatory cell infiltrate
• Balanitis circinata: similar to early stage of keratoderma blenorrhagicum
• Orogenital ulcers demonstrate nonspecific histology, with mixed acute and chronic inflammation at base of shallow ulcers

Immunopathology/special stains

• Special stains help exclude primary infectious processes

Main differential diagnoses

• Psoriasis
• Behçet’s disease
• Infectious ulcers
• Apthous ulcers

Fig 1 Reiter’s syndrome. Eroded erythematous macules on the glans penis. There are several erythematous eroded papules on the mons and in the inguinal folds. The patient also has HIV infection.

Fig 2 Reiter’s syndrome. Evolving lesion showing parakeratosis and a spongiform pustule.


Fig 3 Reiter’s syndrome. Established lesion showing massive parakeratosis and pustules within the stratum corneum.

Fig 4 Reiter’s syndrome. High-power view of underlying spongiosis and neutrophil infiltration.

Fig 5 Reiter’s syndrome. This is a more advanced example showing a massive macropustule.

Fig 6 Reiter’s syndrome. Close-up view of a micropustule.

Fig 7 Reiter’s syndrome. The adjacent epidermis shows marked psoriasiform hyperplasia.
Pityriasis Rubra Pilaris

Definition

• Cutaneous papulosquamous condition presenting as salmon-colored scaling erythema with islands of sparing, perifollicular accentuation, and distinctive scale, and characterized histologically by alternating ortho- and parakeratosis

Clinical features

Epidemiology

• Idiopathic disorder classified into seven types
• Classic adult type
• Atypical adult type
• Juvenile type: presents usually by 2 years of age
• Circumscribed juvenile type
• Atypical juvenile type
• HIV-associated type
• Familial form: autosomal dominant
• No racial preference
• No gender predilection

Presentation

• Salmon-colored papules and plaques in generalized distribution
• Perifollicular accentuation may be prominent
• Islands of sparing characteristic
• Progresses from scalp to toes
• Palmoplantar keratoderma (PPK)
• May progress to erythroderma
• Nail changes, including discoloration and longitudinal ridging
• Atypical adult type demonstrates more eczematous and/or ichthyosiform plaques
• Circumscribed juvenile type exhibits prominent follicular erythematous plaques over knees and elbows
• Atypical juvenile type also shows acral sclerosis
• HIV-associated type additionally manifests nodules, cysts, and pustules

Prognosis and treatment

• Chronic waxing-waning course
• Persistent and lifelong in familial cases
• Remissions may be achieved in sporadic cases, particularly in classic adult type and juvenile type
• Atypical juvenile type associated with a more chronic course
• HIV-associated type generally more refractory to conventional treatment and seems to respond better to anti-HIV therapy
• Occasional cases associated with internal malignancy
• Therapies include topical corticosteroids, topical and systemic retinoids, immunosuppressive agents (e.g., methotrexate, cyclosporine, azathioprine), and new biologic agents (infliximab)
• Complications include functional impairment from PPK, homeostasis abnormalities from erythroderma, risk of infections

Pathology

Histology

• Alternating ortho- and parakeratosis in both vertical and horizontal directions within the stratum corneum
• Perifollicular hyperkeratosis
• Psoriasiform hyperplasia with thick suprapapillary plates, broad rete ridges, and narrow dermal papillae
• Dilated follicles with orthokeratotic plugs
• Variable, usually mild, superficial dermal chronic inflammation
• Acantholysis is some cases

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Psoriasis
• Chronic spongiotic dermatitis

Fig 1 Pityriasis rubra pilaris. Pink (salmon-colored) follicular papules on the upper thigh with minimal scale and intervening areas of normal skin (so-called islands of sparing).
(From Brinster NK: Dermatopathology for the surgical pathologist: a pattern based approach to the diagnosis of inflammatory skin disorders [part I], Adv Anat Pathol 15[2]:76–96, 2008.)

Fig 2 Pityriasis rubra pilaris. Plantar keratoderma.


Fig 3 Pityriasis rubra pilaris. Scanning view showing psoriasiform hyperplasia and a greatly thickened stratum corneum.

Fig 4 Pityriasis rubra pilaris. Characteristic alternating hyperkeratosis and parakeratosis in vertical and horizontal planes.

Fig 5 Pityriasis rubra pilaris. High-power view of Figure 2.

Fig 6 Pityriasis rubra pilaris. In contrast to psoriasis, the suprapapillary plates are thickened.

Fig 7 Pityriasis rubra pilaris. There is a lymphohistiocytic infiltrate in the superficial dermis.

Fig 8 Pityriasis rubra pilaris. Dilated follicle with orthokeratotic plug and perifollicular parakeratosis.
Subcorneal Pustular Dermatosis

Definition

• Sterile intraepidermal pustular dermatitis manifesting as expansile plaques in skin folds; also known as Sneddon-Wilkinson disease

Clinical features

Epidemiology

• Rare
• Most commonly occurs in middle age, reported in children
• Female predilection
• Cause unknown
• Controversial relationship to psoriasis
• Systemic associations include:
• IgA gammopathy/multiple myeloma
• Pyoderma gangrenosum
• Also reported in rheumatoid arthritis, lupus erythematosus, inflammatory bowel disease, thyroid disorders

Presentation

• Superficial pustules on erthythematous plaque
• Annular or serpiginous morphology
• Commonly seen in skin folds: axilla, inguinal area, inframammary, abdomen
• Mild pruritus, burning sensation may be present

Prognosis and treatment

• Chronic, relapsing course
• First-line treatment: dapsone
• Alternative treatments: acitretin, phototherapy, systemic and topical steroids

Pathology

Histology

• Subcorneal collections of neutrophils with rare eosinophils
• Acantholytic cells may be present
• Upper dermal neutrophils, lymphocytes

Immunopathology/special stains

• Direct immunofluorescence studies are negative
• Gram and PAS stains negative for bacteria and fungi

Main differential diagnoses

• Pustular psoriasis
• Pustular drug eruption/acute generalized exanthematous pustular dermatosis
• Bullous impetigo
• Staphylococcal scalded skin syndrome
• Pemphigus foliaceus
• IgA pemphigus
• Candidiasis, dermatophytosis

Fig 1 Subcorneal pustular dermatosis. Bright erythematous, irregular plaques on the neck studded with dozens of fragile few-millimeter pustules or pustular remnants.

Fig 2 Subcorneal pustular dermatosis. The blister forms beneath the stratum corneum and is neutrophil-rich.

Fig 3 Subcorneal pustular dermatosis. Note the acantholysis.
Acute Generalized Exanthematous Pustulosis

Definition

• Superficial pustular hypersensitivity reaction most commonly secondary to medications

Clinical features

Epidemiology

• Any age may be affected
• No gender predilection
• Most commonly occurs within the first few days to one week of beginning a new medication: most common offending medications are beta-lactam antibiotics (penicillin, cephalosporin, vancomycin)
• Also occurs with tetracyclines, calcium channel blockers
• Reported after viral infections

Presentation

• Begins on face, axilla, inguinal areas and rapidly becomes generalized
• May be associated with fever, malaise
• Peripheral neutrophilia, eosinophilia
• Mucous membranes spared

Prognosis and treatment

• Typically resolves within 2 weeks after offending agent discontinued
• Heals with desquamation
• May treat with topical corticosteroids, antihistamines for symptomatic relief until condition clears

Pathology

Histology

• Subcorneal or intraepidermal pustules
• Spongiosis
• Variable acantholysis
• Dermal edema
• Upper dermal neutrophils with admixed eosinophils and lymphocytes
• Leukocytoclastic vasculitis has also been documented

Immunopathology/special stains

• Direct immunofluorescence studies negative
• Gram and PAS stains negative for bacterial and fungal organisms, respectively

Main differential diagnoses

• Pustular psoriasis
• Subcorneal pustular dermatosis
• IgA pemphigus
• Pemphigus foliaceus
• Bullous impetigo
• Staphylococcal scalded skin syndrome
• Candidiasis, dermatophytosis

Fig 1 Acute generalized exanthematous pustulosis. Multiple small pustules within a background of erythema.

Fig 2 Acute generalized exanthematous pustulosis. There is hyperkeratosis and a small intracorneal pustule. The dermis is intensely inflamed.
(Courtesy of T Brenn, MD, PhD; Western General Hospital, Edinburgh, Scotland.)

Fig 3 Acute generalized exanthematous pustulosis. The infiltrate consists of neutrophils, lymphocytes, and histiocytes. Occasional eosinophils are present.
Transient Neonatal Pustular Melanosis

Definition

• Benign vesiculopustular condition of neonates characterized by subcorneal neutrophil pustules

Clinical features

Epidemiology

• Usually noticed at birth
• More common in darker-skinned races

Presentation

• Few to dozens of 1- to 2-mm pustules on generally noninflammatory base
• Scattered, often symmetric distribution, favoring neck and trunk
• Lesions rupture, leaving brown postinflammatory hyperpigmented macules with superficial peeling

Prognosis and treatment

• Benign, self-limited condition
• Recurrent waves of pustules may occur for up to several weeks of life
• Some have suggested that transient neonatal pustular melanosis represents a precocious form of erythema toxicum neonatorum

Pathology

Histology

• Subcorneal neutrophil-rich pustule, eosinophils may be evident
• Mild superficial perivascular lymphocytic infiltrate
• Melanin incontinence in later stages

Immunopathology/special stains

• Special stains negative for pathogenic microorganisms

Main differential diagnoses

• Bacterial impetigo
• Neonatal acne
• Infantile acropustulosis
• Toxic erythema of the neonate
• Arthropod bite reaction

Fig 1 Transient neonatal pustular melanosis. Scattered pustules on the trunk and arm with background hyperpigmented macules and superficial peeling scale.

Fig 2 Transient neonatal pustular melanosis. There is a subcorneal pustule. The adjacent epidermis shows mild spongiosis. Eosinophils are present in the blister cavity and in the dermal infiltrate.
Lichen Simplex Chronicus and Prurigo Nodularis

Definition

• Spectrum of cutaneous conditions representing responses to friction and rubbing

Clinical features

Epidemiology

• Pruritic underlying dermatoses (e.g., atopic dermatitis) or generalized pruritus without a significant primary rash (e.g., pruritus of renal disease) may serve as the trigger for scratching, leading to lichenification or prurigo changes
• May also arise in the setting of psychiatric conditions (e.g., obsessive compulsive disorder)
• Reportedly more frequent in women
• More common in fourth to sixth decades of life
• Prurigo nodule secondary to picking
• Lichen simplex chronicus secondary to rubbing

Presentation

• Thickened, keratotic, erythematous papule or nodule (prurigo nodularis) or plaque(s) (lichen simplex chronicus)
• Accentuated skin markings
• Associated scarring
• Lesions may number from one to hundreds
• Distributed over accessible areas, particularly forearms, legs, neck, less commonly on abdomen, upper back, genitalia; generally spares midback
• Often symmetrical
• Lesions may demonstrate superimposed crusted erosions consistent with excoriation
• Postinflammatory dyspigmentation

Prognosis and treatment

• Risk of superinfection
• If lesions are no longer manipulated, should heal, often with scarring or dyspigmentation
• Treatment of underlying pruritic condition (e.g., pruritic dermatosis or generalized pruritus associated with systemic condition) or psychiatric disorder is crucial
• Dry skin care measures, including use of bland emollients help address possible underlying xerosis
• Topical (or intralesional) corticosteroids or topical calcineurin inhibitors used as antiinflammatory agents
• Sensation-altering topical agents (e.g., capsaicin, menthol, topical oatmeal preparations) to divert attention away from impulse to scratch
• Systemic antihistamines often used
• Phototherapy may be helpful
• Mechanical barrier preparations prevent further manipulation
• Neuropsychiatric medications (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors, gabapentin) effective for some

Pathology

Histology

• Lichen simplex chronicus
• Hyperkeratosis with prominent granular cell layer
• Variable, focal parakeratosis
• Acanthosis with elongation of rete ridges
• Variable spongiosis
• Fibrosis of dermal papillae, atypical myofibroblasts sometimes seen
• Superficial perivascular mixed inflammatory cell infiltrate with eosinophils
• Prurigo nodule
• Hyperkeratosis with acanthosis
• Pseudoepitheliomatous hyperplasia sometimes present
• Variable spongiosis
• Dermal scarring
• Mixed inflammatory cell infiltrate with eosinophils
• Prominent blood vessels (often increased in number)
• Variable peripheral nerve prominence or hyperplasia
• Rarely lymphoid follicles may be seen

Immunopathology

• Not contributory

Main differential diagnoses

• Lichen simplex chronicus
• Psoriasis
• Chronic spongiotic dermatitis
• Prurigo nodule
• Squamous cell carcinoma
• Arthropod bite reaction

Fig 1 Prurigo nodularis. Numerous disseminated, fairly discrete, erythematous, few-centimeter nodules and plaques with superficial erosion in a patient who habitually picked at his legs.


Fig 2 Prurigo nodularis. Somewhat linear, geometric, pink erythematous-scarred plaque with superficial erosion; consistent with self-excoriation.

Fig 3 Lichen simplex chronicus. Hyperkeratosis, hypergranulosis and regular psoriasiform epidermal hyperplasia are visible. Note the vertically orientated collagen fibers in the papillary dermis, a characteristic feature.

Fig 4 Prurigo nodularis. Scanning view showing excoriation and pseudoepitheliomatous hyperplasia. A light lymphocytic infiltrate hugs the borders of the epithelium. There is dermal scarring.
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)

Fig 5 Prurigo nodularis. High-power view showing well-differentiated epithelium and a lymphocytic infiltrate.
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)
Inflammatory Linear Verrucous Epidermal Nevus

Definition

• Typically unilateral lesion with inflamed papules and plaques in a linear distribution. Commonly abbreviated to ILVEN.

Clinical features

Epidemiology

• Usually presents during infancy and childhood (but may arise in adults less commonly)
• More common in girls

Presentation

• May be present at birth; usually develops in first 5 years of life
• Unilateral verrucous, erythematous plaque
• Follows the lines of Blaschko
• Often located on an extremity
• Usually pruritic
• Patients typically healthy otherwise; rare reports of associated skeletal, neurological abnormalities

Prognosis and treatment

• Treatment for symptomatic relief: topical/intralesional corticosteroids
• Removal options for cosmetic reasons: laser therapy, surgery
• Recalcitrant to therapy

Pathology

Histology

• Acanthosis and papillomatosis, with occasional neutrophils in stratum corneum
• Characteristic scale: hyperkeratosis alternates with parakeratosis
• Zones of parakeratosis lack granular layer
• Zones of hyperkeratosis have expanded granular layer
• Superficial perivascular dermatitis

Immunopathology/special studies

• Not contributory

Main differential diagnoses

• Psoriasis
• Eczematous dermatitis
• Verruca

Fig 1 Inflammatory linear verrucous epidermal nevus. Discrete, erythematous psoriasiform plaque in a linear pattern on the arm.
(Courtesy of F Awadalla, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Inflammatory linear verrucous epidermal nevus. Massive increase in thickness of the stratum corneum and marked psoriasiform hyperplasia.

Fig 3 Inflammatory linear verrucous epidermal nevus. Note the alternating parakeratosis and hyperkeratosis.
C
Interface Dermatitis
Erythema Multiforme

Definition

• Hypersensitivity reaction with characteristic targetoid skin lesions and mucosal involvement

Clinical features

Epidemiology

• Etiology, classic viral infection (e.g., herpes simplex, occasionally Mycoplasma infection), or, less often, drugs
• Age range from childhood to elderly; most commonly teens to 40 years old
• No clear racial predilection
• More commonly occurring in males
• Classic culprit drugs inducing erythema multiforme: antibiotics (e.g., penicillin, sulfa-based drugs); anticonvulsants, aspirin and NSAIDs, antituberculous medications

Presentation

• Targetoid lesions characteristic: erythematous to violaceous central slightly raised, few-millimeter papule surrounded by thin pale rim encircled by a few-millimeter erythematous to violaceous outer urticarial rim resembling an iris
• Lesions may be pruritic or feel slightly “burning”
• Lesions can vesiculate
• Koebnerization (induction of lesions at sites of trauma) sometimes observed
• Occasional prodrome with fever, malaise, nausea
• May witness signs and symptoms referable to underlying associated infection
• Oral involvement characterized by plaques, erosions, and ulcerations over lips, gums, and palate; often painful
• Ocular and genital lesions also seen

Prognosis and treatment

• Generally self-limited by few to several weeks
• Occasionally may be persistent
• Supportive care
• Controversy surrounding role of corticosteroids: may help alleviate symptoms

Pathology

Histology

• Variable acanthosis or epidermal atrophy
• Hyperkeratosis often present
• Vacuolar interface changes
• Spongiosis with lymphocytic exocytosis
• Apoptotic keratinocytes (cytoid bodies), can be massive resembling toxic epidermal necrolysis
• Satellite cell necrosis
• Papillary dermal edema with vascular ectasia and endothelial swelling
• Superficial perivascular mild mixed inflammatory infiltrate including scattered eosinophils
• Subepidermal clefting or blister formation and epidermal necrosis in evolved cases
• Classically, parakeratosis is not seen, but may sometimes be evident

Immunopathology

• Not contributory

Main differential diagnoses

• Connective tissue disease (e.g., lupus erythematosus)
• Fixed drug eruption
• Acute graft-versus-host disease
• Stevens-Johnson syndrome/toxic epidermal necrolysis

Fig 1 Erythema multiforme. Early lesions characterized by scattered few-millimeter erythematous macules arising on a typical site, the palm.

Fig 2 Erythema multiforme. Fully evolved palmar lesions with classic targetoid morphology, displaying dusky erythematous central macules surrounded by white rims of pallor, which, in turn, are encircled by thin outer erythematous peripheral rings.



Fig 3 Erythema multiforme. Early lesion showing basal cell hydropic degeneration with cytoid bodies. There is satellite cell necrosis and a light lymphocytic infiltrate.

Fig 4 Erythema multiforme. Low-power view of another early lesion showing hyper- and parakeratosis on the left and marked upper dermal edema on the right.

Fig 5 Erythema multiforme. High-power view of an early lesion showing lymphocytic exocytosis and cytoid bodies.

Fig 6 Erythema multiforme. In this example, there is very extensive interface change.

Fig 7 Erythema multiforme. Early subepidermal vesiculation is present.

Fig 8 Erythema multiforme. This shows a more advanced example with clear blister formation.
Toxic Epidermal Necrolysis/Stevens-Johnson Syndrome

Definition

• Severe hypersensitivity reaction demonstrating prominent mucocutaneous necrosis. The term Stevens-Johnson syndrome is used when less than 30% of the skin is affected, whereas toxic epidermal necrolysis is applied in cases where 30% or more of skin is involved.

Clinical features

Epidemiology

• Predominantly drug-induced
• Common culprit drugs include antibiotics (e.g., sulfa-based drugs, penicillin); anticonvulsants (e.g., carbamazepine, phenytoin, lamotrigine); NSAIDs; and allopurinol
• Usually seen in adults, although any age may be affected
• Occasional cases linked to infectious causes (e.g., Mycoplasma pneumonia )
• No clear racial predilection
• Similar condition may be seen in patients with acute graft-versus-host disease (GVHD), although a drug-induced toxic epidermal necrolysis must be excluded

Presentation

• Prominent involvement of mucosal surfaces (e.g., conjunctiva, oral mucosa, genital mucosa) with erythematous injection, blister formation, and eroded blister remnants
• Erythematous to grayish, often purpuric cutaneous macules (“spots”), sometimes with targetoid morphology coalesce into diffuse dusky erythema
• Typically preceded by prodrome of skin tenderness, anxiety
• Epidermal necrosis leads to central dusky gray coloration, epidermal sloughing, and/or blister formation
• Koebnerization (induction of lesions at sites of trauma) may be observed
• Multisystem involvement possible: gastrointestinal hemorrhage, respiratory failure, renal insufficiency

Prognosis and treatment

• Serious, potentially life-threatening condition, with mortality in greater than one third of patients
• Complications of thermoregulation, electrolyte and fluid homeostasis impairment
• Scarring can occur in eyes and genitourinary tract
• Sepsis may lead to death
• Supportive care in a burn unit
• Controversy surrounding role of corticosteroids: may help alleviate symptoms
• Intravenous immunoglobulin use prompted by elucidation of Fas-ligand pathophysiologic mechanism
• Thalidomide found to increase risk of death
• Judicious antibiotic therapy guided by cultures

Pathology

Histology

• Severe vacuolar interface change often with subepidermal vesiculation
• Festooning (preservation of dermal papillae)
• Massive apoptosis often affecting the entire epidermis/epithelium
• Adnexal involvement, particularly sweat gland
• Satellite cell necrosis with lymphocytic exocytosis in early lesion
• Superficial perivascular mild mixed inflammatory infiltrate including scattered eosinophils
• “Jelly-roll” technique for quick diagnosis: sloughed skin can be collected by wrapping it around a cotton swab stick; frozen sections reveal full-thickness epidermal necrosis

Immunopathology

• Not contributory

Main differential diagnoses

• Erythema multiforme
• Severe acute GVHD
• Staphylococcal scalded skin syndrome
• Paraneoplastic pemphigus

Fig 1 Toxic epidermal necrolysis. Denudation and bleeding over the back of an adult woman with toxic epidermal necrolysis suspected to be due to an anticonvulsant.


Fig 2 Toxic epidermal necrolysis. Low-power view showing a cell-free subepidermal blister.

Fig 3 Toxic epidermal necrolysis. The blister is completely empty, dermal papillae are preserved, and the roof is necrotic.

Fig 4 Toxic epidermal necrolysis. High-power view of the roof showing full thickness apoptosis.

Fig 5 Toxic epidermal necrolysis. High-power view of a sweat duct with focal apoptosis and scattered chronic inflammatory cells.

Fig 6 Toxic epidermal necrolysis. High-power view of an affected hair follicle.

Fig 7 Toxic epidermal necrolysis. The adjacent nonblistered skin shows massive apoptosis with lymphocytes tagging the interface between the epidermis and dermis.
Lupus Erythematosus

Definition

• Multisystem autoimmune condition that classically features mucocutaneous manifestations

Clinical features

Epidemiology

• Female predilection
• Usually presents in young adulthood, in the third to fifth decades

Presentation

• From dermatologic standpoint, three classic forms recognized: discoid lupus erythematosus (DLE); subacute cutaneous lupus erythematosus (SCLE); systemic lupus erythematosus (SLE)
• DLE:
• Photodistributed circular to oval erythematous plaques with hyperkeratotic, adherent carpet-tack scale, telangiectasia
• Distributed commonly on the face, chest, upper trunk, and arms
• May demonstrate verrucous surface or be hypertrophic
• Scarring common
• Tumid lupus erythematosus lacks significant epidermal change
• SCLE:
• Photodistributed eruption of psoriasiform or annular polycyclic plaques
• Commonly symmetrically distributed on the face, chest, upper trunk, and arms
• Photosensitivity prominent
• SLE: classically defined as the presence of 4/11 criteria:
• Malar erythema
• DLE lesions
• Photosensitivity
• Arthritis
• Serositis
• Renal involvement (e.g., nephritis)
• Oral ulcers
• Hematologic abnormalities (e.g., cytopenias)
• Positive ANA
• Neurologic abnormalities (e.g., seizures)
• Other autoantibodies (e.g., anti–Smith antibody)
• SLE also commonly associated with Raynaud’s phenomenon, vasculitis, alopecia, nail dystrophy, periungual telangiectasias/erythema
• SLE may coexist with other autoimmune diseases, such as Sjögren’s syndrome, antiphospholipid antibody syndrome
• Neonatal LE (NLE) occurs in babies of mothers with connective tissue disease (sometimes latent or undiagnosed), presents at birth with annular polycyclic plaques similar to SCLE (with which it shares Ro-positivity), and is associated with heart block; lesions on head and neck

Prognosis and treatment

• DLE complicated by scarring, risk for development of squamous cell carcinoma and basal cell carcinoma; with generalized lesions, approximately 5% risk of progression to SLE
• SCLE markedly photosensitive; associated risk of Sjögren’s syndrome or rheumatoid arthritis; may eventuate into SLE in half of cases
• SLE prognosis and course dependent upon degree and nature of internal involvement; causes of death include nephritis, infections, or CNS involvement
• NLE lesions typically regress by 6 months of age, but cardiac conduction defects persist
• Photoprotection is paramount to management of all forms of LE
• Antimalarials, including hydroxychloroquine, chloroquine, and quinacrine most commonly used for treatment; topical/intralesional corticosteroids
• Other immunomodulatory agents include methotrexate, cyclophosphamide, intravenous immunoglobulins

Pathology

Histology

• DLE:
• Hyperkeratosis
• Often epidermal atrophy, occasionally irregular acanthosis
• Basement membrane zone thickening
• Vacuolar interface dermatitis sometimes with cytoid bodies
• Lichenoid and superficial and deep, perivascular and periadnexal lymphocytic inflammation
• Interstitial mucin deposition; marked in tumid variant
• Melanin pigment incontinence
• Telangiectasia
• Follicular dilatation with keratin plugging
• SCLE:
• Hyperkeratosis, occasional parakeratosis
• Epidermal atrophy
• Vacuolar interface changes with apoptosis and satellite cell necrosis
• Lichenoid and superficial and deep, perivascular and periadnexal lymphocytic inflammation; however, sometimes infiltrate is minimal
• Interstitial mucin deposition
• Melanin pigment incontinence
• SLE:
• Changes of DLE or SCLE depending upon clinical morphology; features are sometimes subtle with mild interface change and epidermal atrophy only

Immunopathology/special stains

• Mucin stains highlight interstitial mucin
• Thickened basement membrane zone highlighted by PAS stain
• Direct immunofluorescence: IgG (most specific), IgM (most common), C3 immunoreactants along dermal–epidermal junction

Main differential diagnoses

• Dermatomyositis
• Mixed connective tissue disease
• Polymorphous light eruption
• B-cell lymphoma
• Jessner’s lymphocytic infiltrate
• Pseudolymphoma
• Lichen planus

Fig 1 Chronic cutaneous (discoid) lupus erythematosus. Discrete hypopigmented plaques with central erythema, fibrosis, and slight scale. The border is hyperpigmented.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Subacute cutaneous lupus erythematosus. Annular, erythematous, scaly papules and plaques on sun-exposed areas.

Fig 3 Systemic lupus erythematosus. Young woman with malar erythema (“butterfly rash”) and macular erythema on sun-exposed sites of chest and extensor arms. Note dorsal hand is also involved with erythema in the interphalangeal areas and around nail folds. This patient was anti–Ro positive.

Fig 4 Lupus vasculitis. Reticulated erythema with hyperkeratosis and multifocal ulceration on the leg of a woman with systemic lupus erythematosus.

Fig 5 Discoid lupus erythematosus. Scanning view showing hyperkeratosis and marked follicular plugging. There is a dense perivascular and periadnexal lymphoid infiltrate.

Fig 6 Discoid lupus erythematosus. High-power view showing follicular involvement. Scarring alopecia is an important complication.

Fig 7 Discoid lupus erythematosus. High-power view showing interface change.

Fig 8 Discoid lupus erythematosus. Note the basement membrane thickening and edema.

Fig 9 Subacute cutaneous lupus erythematosus. At low power, the features are subtle. There is slight hyperkeratosis, and a perivascular chronic inflammatory cell infiltrate is present.
(Courtesy of E Calonje, MD; St John’s Dermatology Center, London.)

Fig 10 Subacute cutaneous lupus erythematosus. Higher-power view showing interface change.
(Courtesy of E Calonje, MD; St John’s Dermatology Center, London.)

Fig 11 Subacute cutaneous lupus erythematosus. High-power view showing numerous cytoid bodies and satellite cell necrosis.
(Courtesy of E Calonje, MD; St John’s Dermatology Center, London.)

Fig 12 Systemic lupus erythematosus. There is mild interface change. The dermis is edematous, and there is an interstitial lymphohistiocytic infiltrate. Note the cytoid body.

Fig 13 Lupus erythematosus. Alcian blue stain highlights increased mucin in the reticular dermis.

Fig 14 Lupus erythematosus. Diastase-PAS stain highlights a thickened basement membrane.

Fig 15 Direct immunofluorescence. Granular IgM deposition along the basement membrane zone.
Dermatomyositis

Definition

• Autoimmune condition characterized by inflammatory myopathy and skin rash

Clinical features

Epidemiology

• Female predilection
• Adult and juvenile forms recognized

Presentation

• Erythema in a shawl-like distribution over upper chest and upper back (typically in a photodistribution)
• Heliotrope (purplish) color over upper eyelids
• Gottron’s papules: erythematous to violaceous, thin few-millimeter papules over interphalangeal joints and metacarpophalangeal joints of dorsal hands, may overlie other joints
• Poikiloderma: telangiectasias, atrophy, hyperpigmentation, and hypopigmentation
• Scalp pruritus common, alopecia
• Calcinosis, sometimes with cutaneous ulceration and extrusion through the skin, can be present, particularly in children
• Raynaud’s phenomenon not uncommon
• Periungual erythema, splinter hemorrhages, and telangiectasia
• Proximal muscle weakness typically is present, although dermatomyositis sine myositis can occur (skin lesions without myositis for at least 6 months)
• Raised creatine kinase, aldolase
• Overlap syndromes (e.g., dermatomyositis with scleroderma)
• Lung and heart involvement in some patients

Prognosis and treatment

• For patients over age 40, increased risk of internal malignancy, particularly breast and gynecological cancers in women, typically seen within the first 2 years of presentation
• Prednisone, other immunosuppressants (including azathioprine, methotrexate), antimalarials, intravenous immunoglobulins
• Topical corticosteroids, photoprotection

Pathology

Histology

• Hyperkeratosis and epidermal atrophy
• Loss of rete ridges
• Vacuolar interface dermatitis
• Apoptotic keratinocytes (cytoid bodies)
• Pigment incontinence
• Superficial perivascular lymphocytic infiltrate
• Mild dilatation of superficial vessels, occasional thrombotic changes
• Variable superficial dermal edema
• Dermal mucin deposition often present
• Gottron’s papules show hyperkeratosis, variable papillomatosis and acanthosis, mild interface change
• Muscle changes include muscle necrosis and regeneration, chronic inflammatory cell infiltrate around blood vessels and muscle fibers

Immunopathology/special stains

• Direct immunofluorescence: granular IgG and C3 along dermal–epidermal junction
• Blood vessel wall complement deposits (C5-C9) sometimes present
• Anti–nuclear factor often positive
• Various nuclear antibodies; e.g., anti–Mi-2, highly specific but poor sensitivity

Main differential diagnoses

• Lupus erythematosus
• Mixed connective tissue disease
• Erythema multiforme
• Drug reaction

Fig 1 Dermatomyositis. Coalescent scaling macular and papular erythema in a shawl-like distribution.

Fig 2 Dermatomyositis. Gottron’s pink erythematous few-millimeter flat-topped papules over the dorsal joints of the hands.


Fig 3 Dermatomyositis. Periungual erythema and telangiectasia with cuticular hyperkeratosis.

Fig 4 Dermatomyositis. Poikilodermatous change and alopecia on the scalp.

Fig 5 Dermatomyositis. Hyperkeratosis and an irregular epidermis. A perivascular chronic inflammatory infiltrate is present in the superficial dermis. Note the edema.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 6 Dermatomyositis. Focal liquefactive degeneration of the basal layer is present, and there are cytoid bodies. Red cell extravasation is evident.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 7 Dermatomyositis. This field shows focal calcification in the deep dermis.
Graft-Versus-Host Disease (GVHD)

Definition

• Condition of grafted transplant immune tissue reacting against host tissue, usually in the context of bone marrow transplant, and affecting skin and other organ systems, particularly gastrointestinal

Clinical features

Epidemiology

• Most commonly bone marrow transplant recipient patients
• Also in recipients of certain solid organ transplants containing lymphoid tissue (e.g., liver) and nonirradiated blood products
• Risk of developing GVHD increases with age

Presentation

• Acute form presents within 100 days; chronic forms arise after 100 days
• Acute form: variably tender or pruritic, macular erythema or thin coalescent erythematous plaques, characteristically beginning around ears, palms, soles, and spreading centripetally to involve trunk; usually arising approximately three weeks posttransplantation; may progress into exfoliative erythroderma, bullae
• Hyperacute form uncommon, arises within two weeks of transplant, with associated erythroderma, fever
• Hepatitis is a common associated complication in acute form
• Enteritis, with diarrhea, abdominal pain also seen in acute form
• Chronic form lichenoid or sclerodermoid; may arise without prior acute phase
• Lichenoid chronic GVHD demonstrates coalescent, diffusely distributed thin polygonal erythematous few-millimeter papules
• Sclerodermoid chronic GVHD demonstrates diffuse skin induration and tightening, complicated by joint contractures
• Chronic form can be associated with ocular problems arising from lack of tear secretion, dysphagia, and dyspnea

Prognosis and treatment

• Challenging to treat effectively
• Decrease in immunosuppression may help
• Prophylactic prebone marrow transplant immunosuppressive regimens (e.g., cyclosporine) may help prevent GVHD
• Topical corticosteroids, cyclosporine, methotrexate, mycophenolate mofetil, UVA1, PUVA, photophoresis, rituximab, and antithymocyte immunoglobulin all used with variable success

Pathology

Histology

• Variable hyperkeratosis, acanthosis, or epidermal atrophy (in chronic form)
• Interface inflammation with dyskeratosis (cytoid bodies) and lymphocyte exocytosis
• Satellitosis describes apoptotic keratinocyte flanked by lymphocytes (but this is not always seen)
• Subepidermal clefting can be present
• More severe form may resemble toxic epidermal necrolysis with subepidermal blistering
• Variable spongiosis and adnexal involvement
• Eosinophils may be present
• Grover-like morphology (acantholytic dyskeratosis) may also be seen
• Lichenoid chronic GVHD shows band-like lymphocytic infiltrate with interface changes indistinguishable from lichen planus
• Sclerodermoid chronic GVHD shows diffuse dermal sclerosis
• Melanin incontinence
• Histologic grading schemes rating degree of interface change, clefting, spongiosis, and dyskeratosis in use

Immunopathology

• GVHD mediated by donor CD3+ T cells

Main differential diagnoses

• Erythema multiforme (acute GVHD)
• Cutaneous eruption of lymphocyte recovery (acute GVHD)
• Adverse drug reaction (acute GVHD)
• Toxic epidermal necrolysis (acute GVHD)
• Connective tissue disease (acute GVHD)
• Lichen planus (lichenoid chronic GVHD)
• Scleroderma/morphea (sclerodermoid chronic GVHD)

Fig 1 Acute graft-versus-host disease. Characteristic involvement of the posterior scalp and ear.


Fig 2 Chronic graft-versus-host disease (GVHD). Posterior view of the lower legs of sclerodermoid GVHD demonstrating skin sclerosis with areas of erythema and dyspigmentation.

Fig 3 Acute graft-versus-host disease. Scanning view showing hyperkeratosis, epidermal atrophy, and a dense superficial dermal infiltrate.

Fig 4 Acute graft-versus-host disease. There is hyperkeratosis, epidermal atrophy, cytoid bodies, and interface change.

Fig 5 Lichenoid graft-versus-host disease. This example shows hyperkeratosis, hypergranulosis, and irregular sawtooth acanthosis.

Fig 6 Lichenoid graft-versus-host disease. Note the interface change and cytoid bodies.

Fig 7 Sclerodermoid chronic graft-versus-host disease. There is hyperkeratosis, hypergranulosis, and acanthosis. Note the marked dermal sclerosis.
Interface Dermatitis of HIV Infection

Definition

• Interface dermatitis seen in HIV-infected individuals

Clinical features

Epidemiology

• Occurs in the setting of HIV infection, usually advanced disease
• May be a drug reaction (e.g., to nonsteroidals and trimethoprim-sulfamethoxazole)

Presentation

• Develops on sun-exposed areas (e.g., face, extensor arms, neck, and chest).
• May progress to involve sun-protected sites
• Mucosal involvement typically limited to the lower lip
• Erythematous to violaceous patches and plaques
• Can be pruritic, excoriations common
• Resolves with loss of pigment in darker-skinned individuals

Prognosis and treatment

• Chronic condition
• Treatment with topical steroids
• Withdrawal of photosensitizing medications when possible
• Sun protection

Pathology

Histology

• Interface alteration along the dermal–epidermal junction
• Necrotic keratinocytes, cytoid bodies, and lymphocytes at the dermal–epidermal junction
• Lichenoid lymphohistiocytic infiltrate, with occasional plasma cells (but typically, this is a cell-poor interface dermatitis)

Immunopathology/special studies

• Not contributory

Main differential diagnosis

• Other interface dermatitides including dermatomyositis, subacute lupus erythematosus, acute graft-versus-host disease

Fig 1 Interface dermatitis of HIV infection. Erythematous, well-demarcated, lichenified plaques on the posterior neck in a man with HIV/AIDS. Note the marked hypopigmentation and photodistribution.

Fig 2 Interface dermatitis of HIV infection. Mild hyperkeratosis and hypergranulosis. The epidermis appears flattened. A band-like infiltrate is present in the superficial dermis.

Fig 3 Interface dermatitis of HIV infection. Interface change is evident. The infiltrate consists of lymphocytes, histiocytes, and scattered plasma cells.

Fig 4 Interface dermatitis of HIV. High-power view showing basal cell hydropic degeneration.

Fig 5 Interface dermatitis of HIV. There is marked pigment incontinence.

Fig 6 Interface dermatitis of HIV. This example is associated with a heavy lymphocyte and plasma cell infiltrate.
Pityriasis Lichenoides

Definition

• Cutaneous lymphocyte-mediated condition with two forms recognized: acute (pityriasis lichenoides et varioliformis acuta [PLEVA]) and chronic (pityriasis lichenoides chronica [PLC]).

Clinical features

Epidemiology

• Acute: children, teens, young adults, with slight male predilection; no clear racial predisposition
• Chronic: adults

Presentation

• Acute:
• Few to hundreds of often crusted, papulonodules, ranging from a few millimeters to a few centimeters, distributed over the trunk and extremities
• Individual lesions evolve from vesiculation to central necrosis, followed by scarring; variably pruritic
• Typically abrupt onset
• May have associated fever, constitutional symptoms
• Chronic:
• Fine, scaly erythematous papules to thin plaques distributed over trunk and proximal extremities
• Occasionally pruritic

Prognosis and treatment

• Acute: benign condition; lesions may evolve into PLC; therapeutic options include topical or systemic corticosteroids, tetracyclines, erythromycin, PUVA
• Reports of evolution into cutaneous lymphoma
• Chronic: fundamentally benign condition

Pathology

Histology

• Acute:
• Acanthosis, parakeratosis often with ulceration
• Interface change
• Spongiosis, intracellular edema, lymphocytic exocytosis
• Characteristically dense, wedge-shaped, lymphohistiocytic infiltrate occupying the superficial to deep dermis
• Dermal edema and erythrocyte extravasation
• Vasculitis may exceptionally be evident
• Chronic:
• Hyperkeratosis, parakeratosis, and mild acanthosis
• Focal interface change with apoptosis
• Mild spongiosis
• Superficial dermal lymphohistiocytic infiltrate with exocytosis

Immunopathology

• Not contributory

Main differential diagnoses

• Arthropod bite reaction
• Mycosis fungoides
• Lymphomatoid papulosis
• Pityriasis rosea (PLC)
• Nummular eczema (PLC)

Fig 1 Pityriasis lichenoides et varioliformis acuta. Polymorphous, erythematous, edematous, variably sized papules distributed on the arm.

Fig 2 Pityriasis lichenoides chronica. Multiple erythematous papules with slight scale on the trunk.
(From the collection of the late NP Smith, MD; the Institute of Pathology, London.)

Fig 3 Pityriasis lichenoides et varioliformis acuta. Low-power view of an evolving lesion showing parakeratosis and intense epidermal and upper dermal inflammation.

Fig 4 Pityriasis lichenoides et varioliformis acuta. High-power view of Figure 3 showing intraepidermal edema, lymphocyte exocytosis, florid basal cell hydropic degeneration, and multiple cytoid bodies.

Fig 5 Pityriasis lichenoides et varioliformis acuta. Medium-power view showing vascular dilatation and endothelial swelling. There is a heavy lymphohistiocytic infiltrate.

Fig 6 Pityriasis lichenoides et varioliformis acuta. High-power view of lymphocytes with histiocytes and one or two eosinophils.

Fig 7 Pityriasis lichenoides chronica. Mild epidermal acanthosis with parakeratosis and mildly dense superficial perivascular lymphocytic infiltrate with occasional exocytosis into the epidermis.

Fig 8 Pityriasis lichenoides chronica. High-power view of Figure 7 showing focal interface change, exocytosis, and overlying parakeratosis.

Fig 9 Pityriasis lichenoides chronica. Medium-power view showing hyperkeratosis with focal parakeratosis, acanthosis with lymphocytic exocytosis and focal interface change. Note the upper dermal edema and erythrocyte extravasation.
D
Lichenoid Dermatitis
Lichen Planus

Definition

• Mucocutaneous condition characterized by pruritic papules and plaques clinically and histologically by lichenoid chronic inflammation

Clinical features

Epidemiology

• Association with hepatitis C
• No race or gender predilection; any age can be affected

Presentation

• Pruritic polygonal purple papules and plaques (5 “Ps”)
• Distribution over flexural wrists, ankles, arms, legs, trunk, genitalia, oral mucosa
• Wickham’s striae: reticulate network of lacy white scaling seen over cutaneous papules and buccal mucosae
• Nail involvement by pterygium
• Lichenoid drug eruption similar, but generally may be photodistributed, lacks both nail involvement, and Wickham’s striae
• Hypertrophic variant with particularly thickened, often coalescent papules and nodules, common on lower legs

Prognosis and treatment

• Chronic waxing-waning course
• Treatment options include topical corticosteroids, systemic retinoids, photo(chemo)therapy

Pathology

Histology

• Hyperkeratosis and irregular sawtooth acanthosis
• Wedge-shaped hypergranulosis
• Basal cell hydropic degeneration and squamatization
• Lichenoid (band-like) chronic inflammatory infiltrate within the superficial dermis lying parallel to the overlying epidermis, consisting of lymphocytes and histiocytes
• Plasma cells and eosinophils generally absent
• Apoptotic (“cytoid,” “Civatte,” “colloid”) bodies
• Hypertrophic variant demonstrates particularly prominent hyperkeratosis and acanthosis

Immunopathology/special stains

• Direct immunofluorescence: fibrinogen in linear or shaggy pattern along dermal–epidermal junction; cytoid bodies may be positive for IgM

Main differential diagnoses

• Lichenoid drug eruption
• Fixed drug reaction
• Lichenoid keratosis
• Lichen striatus
• Lichenoid mycosis fungoides
• Chronic graft-versus-host disease (lichenoid)
• Squamous cell carcinoma or pseudoepitheliomatous hyperplasia can mimic hypertrophic lichen planus

Fig 1 Lichen planus. Polygonal, violaceous flat-topped papules on the dorsal hand.
(From the collection of the late NP Smith, MD; the Institute of Pathology, London.)

Fig 2 Lichen planus. Note the ulcer on the buccal mucosa. There are reticulated white papules on the upper gingiva/hard palate.

Fig 3 Hypertrophic lichen planus. Violaceous, discrete plaques with thick adherent scale on the lower leg.


Fig 4 Lichen planus. There is hyperkeratosis, hypergranulosis, and irregular acanthosis.

Fig 5 Lichen planus. Note the basal cell hydropic degeneration.

Fig 6 Lichen planus. This field shows a subepidermal cleft filled with fibrin.

Fig 7 Lichen planus. There are conspicuous cytoid bodies.

Fig 8 Lichen planus. Hypertrophic variant showing pseudoepitheliomatous hyperplasia and massive hyperkeratosis.

Fig 9 Lichen planus. Direct immunofluorescence showing fibrinogen in a linear pattern along the dermal–epidermal junction.
Lichenoid Drug Reaction

Definition

• Cutaneous hypersensitivity reaction to a medication manifesting with lichen planus–like morphology; sometimes interface changes predominate

Clinical features

Epidemiology

• Usually adults affected
• More commonly reported in women
• Common drugs implicated include angiotensin converting enzyme-inhibitors, calcium channel blockers, beta-blockers, and thiazides; other causative drugs reported include (although not limited to) furosemide, tetracycline, hydroxyurea, imatinib, proton pump inhibitors, gold, allopurinol
• May or may not be photoexacerbated

Presentation

• Eruption typically starts from weeks to months following administration of medication
• Erythematous to violaceous few-millimeter papules coalescent into larger plaques
• Often distributed over extremities, trunk
• May also be photodistributed (lichenoid photodrug)
• Variable pruritus
• Oral lesions sometimes seen

Prognosis and treatment

• Most cases self-limited with discontinuation of the culprit medication
• Topical or systemic corticosteroids, antihistamines used in some instances

Pathology

Histology

• Hyperkeratosis with focal parakeratosis, irregular acanthosis
• Wedge-shaped hypergranulosis
• Basilar epidermal squamatization
• Cytoid bodies usually evident and may be seen in the upper reaches of the epidermis
• Band-like predominantly lymphocytic infiltrate within the papillary dermis
• Admixed scattered perivascular eosinophils usually identified
• Plasma cells often seen
• Melanin pigment incontinence, commonly marked

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Lichenoid keratosis
• Lichen planus
• Fixed drug eruption
• Lichenoid graft-versus-host disease

Fig 1 Lichenoid drug reaction. Erythematous papules and plaques in a photodistribution on the upper chest of an elderly woman taking a thiazide diuretic.

Fig 2 Lichenoid drug reaction. There is hyperkeratosis, hypergranulosis, irregular acanthosis, and a band-like chronic inflammatory cell infiltrate indistinguishable from lichen planus.


Fig 3 Lichenoid drug reaction. Note the interface change with cytoid bodies. This example was associated with use of a thiazide diuretic.

Fig 4 Beta-blocker drug reaction. There is hyperkeratosis, irregular acanthosis, and a perivascular and superficial band-like inflammatory cell infiltrate.

Fig 5 Beta-blocker drug reaction. Higher-power view of Figure 4. There are interface changes. The dermal infiltrate consists mostly of lymphocytes.

Fig 6 Beta-blocker drug reaction. Note the vascular ectasia and dermal cytoid bodies.

Fig 7 Beta-blocker drug reaction. High-power view showing basal cell hydropic degeneration.
Fixed Drug Eruption

Definition

• Cutaneous reaction to a drug that recurs at the same place(s) upon repeated exposure to that drug

Clinical features

Epidemiology

• Adults and children affected
• No documented racial predilection
• Equal sex incidence

Presentation

• Violaceous to brown, often circular or oval macule or patch a few millimeters to several centimeters in diameter
• Triggered by exposure to long list of possible medications, commonly antibiotics (e.g., penicillins, sulfa-based), phenolphthalein (laxative), NSAIDs, anticonvulsants, phenothiazines
• Most common cause is trimethoprim-sulfamethoxazole
• Disseminated lesions possible
• Linear, bullous, eczematous, urticarial variants recognized
• Extremities particularly affected
• Mucosal membranes common sites
• Reexposure to medication causes recurrence of lesions, increased prominence of old lesions
• Occasionally systemic, constitutional symptoms occur

Prognosis and treatment

• Recurrent with reexposure to drug
• Often leaves hyper- (or hypo-) pigmentation
• Avoidance of the culprit drug constitutes the mainstay of treatment

Pathology

Histology

• Hyperkeratosis
• Variable acanthosis
• Interface change often with numerous cytoid bodies
• Mixed dermal infiltrate of lymphocytes, histiocytes, neutrophils, and sometimes conspicuous eosinophils
• Pigment incontinence (may be all that is seen in old lesions)
• In recurrent lesions, melanophages at deeper levels in the dermis may be seen (in addition to more superficial findings)

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Lichen planus
• Lichenoid drug eruption
• Lichenoid keratosis
• Erythema multiforme
• Lupus erythematosus
• Graft-versus-host disease
• Erythema dyschromicum perstans (ashy dermatosis)

Fig 1 Fixed drug eruption. Erythematous to violaceous plaque on the mandible of a woman secondary to fluconazole. Early stage lesion.

Fig 2 Fixed drug eruption. Multiple hyperpigmented circumscribed macular lesions. There is a slight scale. Later stage lesions.

Fig 3 Fixed drug eruption. Slight hyperkeratosis and mild acanthosis. Interface change is evident, and there is a superficial perivascular and interstitial chronic inflammatory cell infiltrate.


Fig 4 Fixed drug eruption. High-power view showing interface change and marked apoptosis.

Fig 5 Fixed drug eruption. Note the basal cell hydropic degeneration.

Fig 6 Fixed drug eruption. There is high level apoptosis, which may be related to the acrosyringium. There is pigment incontinence.

Fig 7 Fixed drug eruption. Scattered eosinophils, lymphocytes, and a few neutrophils are evident.
Lichen Striatus

Definition

• Papulosquamous skin condition characterized by numerous coalescent tiny papules arranged characteristically along lines of Blaschko

Clinical features

Epidemiology

• Most commonly seen in children, although any age may be affected
• No clear racial predilection
• Possible female predilection
• Case clustering
• Seasonal variation

Presentation

• Numerous small (1- to 3-mm) skin-colored to scaly, hyperpigmented, brownish papules coalescent into linear plaques
• Arranged along lines of Blaschko (cutaneous bands of embryologic development)
• Usually unilateral, rarely may be bilateral
• Papules are flat-topped or rough-surfaced
• Distributed over extremities, particularly the leg
• Usually asymptomatic, occasionally slightly pruritic
• Some reports suggest that these lesions may koebnerize

Prognosis and treatment

• Self-limited condition, with lesions typically resolving by 1 year
• Therapeutic options include topical corticosteroids, topical retinoids, and topical calcineurin inhibitors

Pathology

Histology

• Parakeratosis, mild acanthosis
• Spongiotic dermatitis
• Interface change with cytoid bodies
• Satellite cell necrosis
• Superficial dermal, perivascular and periadnexal lymphohistiocytic infiltrate
• Pigment incontinence

Immunopathology/special stains

• Not contributory

Main differential diagnosis

• Lichen planus

Fig 1 Lichen striatus. Erythematous scaly papules in a linear distribution on the thigh.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Lichen striatus. Obliquely cut section. There is marked hyperkeratosis with parakeratosis, acanthosis, inflammation, and pigment incontinence.
(Courtesy of S Lyle, MD; Beth Israel Deaconess Medical Center, Boston.)

Fig 3 Lichen striatus. Note the spongiosis and lymphocytic exocytosis.
(Courtesy of S Lyle, MD; Beth Israel Deaconess Medical Center, Boston.)


Fig 4 Lichen striatus. Marked interface changes with basal cell hydropic degeneration and conspicuous cytoid bodies.
(Courtesy of S Lyle, MD; Beth Israel Deaconess Medical Center, Boston.)

Fig 5 Lichen striatus. This field highlights the massive pigment incontinence.

Fig 6 Lichen striatus. Spongiosis predominates in this area.

Fig 7 Lichen striatus. Interface change with satellite cell necrosis.

Fig 8 Lichen striatus. There is a dense dermal lymphohistiocytic infiltrate.
Lichen Nitidus

Definition

• Benign skin condition characterized by numerous papules with typical skin morphology and characteristic histopathology

Clinical features

Epidemiology

• Commonly seen in children, young adults
• No clear racial predilection
• No clear gender predilection

Presentation

• Numerous tiny skin-colored to hyperpigmented papules
• Papules typically flat-topped; Wickham’s striae absent
• Distributed over ventral wrists, trunk, genitalia
• Usually asymptomatic, occasionally slightly pruritic
• Lesions may koebnerize (induction of lesions at sites of trauma)
• In some cases, lesions can be arranged in linear or disseminated pattern
• Vesiculation or perforation of lesions reported
• Mucosal involvement is almost invariably absent

Prognosis and treatment

• Idiopathic condition
• Topical and systemic corticosteroids, topical and systemic retinoids, topical calcineurin inhibitors, and phototherapy all tried, with variable response
• Occasional association with atopic dermatitis reported

Pathology

Histology

• Sharply delineated lesion with parakeratosis and epidermal atrophy
• Mild interface change with few cytoid bodies
• Lymphohistiocytic infiltrate filling the papillary dermis and bordered by elongated epidermal rete ridges resembling a “ball-in-claw” pattern
• Epithelioid cells, multinucleate giant cells, occasionally noncaseating granulomata

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Lichen planus
• Lichen striatus

Fig 1 Lichen nitidus. Cluster of dozens of minute, 1- to 2-mm skin-colored to slightly hypopigmented papules over the lateral malleolus of a child.

Fig 2 Lichen nitidus. Typical low-power morphology. The infiltrate occupies no more than a couple of dermal papillae. Note the claw-like extensions of the adjacent rete ridges. The overlying epidermis is hyperkeratotic and attenuated.

Fig 3 Lichen nitidus. High-power view. The infiltrate consists of lymphocytes and histiocytes. There is an ill-formed granulomatous element in the upper field.
Erythema Dyschromicum Perstans (ASHY DERMATOSIS)

Definition

• Idiopathic cutaneous pigmentary condition; relationship, if any, to lichen planus is uncertain

Clinical features

Epidemiology

• Dark-skinned persons mostly affected, particularly those from regions of Latin America and Asia
• Slight predilection for females
• Generally presents in childhood or early adulthood

Presentation

• Condition usually arises slowly, as oval grayish macules and patches with raised erythematous border
• Evolves into bluish-gray to brownish macules and patches in photodistribution on face, arms, upper trunk
• Lesions usually asymptomatic
• Spares mucosae

Prognosis and treatment

• Spontaneous resolution over few years more likely in cases arising in childhood
• Clofazamine is therapeutic agent of choice
• Photoprotection important aspect of management
• Hydroquinone bleaching creams and laser therapy also offered as treatment

Pathology

Histology

• Hyperkeratosis
• Variable epidermal atrophy
• Lichenoid lymphocytic infiltrate with vacuolar interface change in active lesions, particularly in specimens taken from erythematous border; cytoid bodies
• Infiltrate usually resolves with advanced lesions
• Pigment incontinence with prominent melanophages in the superficial dermis

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Postinflammatory hyperpigmentation
• Lichen planus pigmentosus
• Lichenoid drug eruption
• Fixed drug eruption
• Acute graft-versus-host disease

Fig. 1 Erythema dyschromicum perstans. Irregular brown-black patches on the left flank of a Hispanic man.

Fig 2 Erythema dyschromicum perstans. High-power view of basal cell hydropic degeneration.
Lichenoid Keratosis

Definition

• Common, nonneoplastic, generally solitary lichen planus–like scaly lesion

Clinical features

Epidemiology

• Adults
• No gender predilection
• More common in light-skinned persons

Presentation

• Usually solitary
• Skin-colored to erythematous to brown-colored thin few-millimeters to over-a-centimeter plaque
• Often translucent with telangiectasias
• Clinically can resemble basal cell carcinoma or squamous cell carcinoma
• Located commonly on the face, trunk, or upper extremity
• Variably pruritic

Prognosis and treatment

• Benign lesion
• Speculation that in some instances, the lesion might represent regression of an actinic lentigo or seborrheic keratosis
• Often biopsied for clinical suspicion of a nonmelanoma skin cancer (commonly basal cell carcinoma)

Pathology

Histology

• Hyperkeratosis, hypergranulosis, and variable acanthosis or atrophy
• Focal parakeratosis
• Interface change with cytoid bodies
• Cytoid bodies high in epidermis
• Dense lymphohistiocytic inflammation in a horizontal band-like pattern apposed to and parallel to the overlying epidermis
• Small numbers of eosinophils and plasma cells often present
• Melanin pigment incontinence

Immunopathology/special stains

• Not contributory

Main differential diagnoses

• Lichen planus
• Lichenoid drug eruption
• Lichenoid actinic keratosis
• Keratosis lichenoides chronica
• Fixed drug eruption

Fig 1 Lichenoid keratosis. Circumscribed, erythematous slightly raised papular lesion with overlying scale.

Fig 2 Lichenoid keratosis. The epidermis shows hyperkeratosis with variable slight acanthosis and thinning. Subepidermal vesiculation is evident on the right side of the image.

Fig 3 Lichenoid keratosis. Hyperkeratosis, focal parakeratosis, and extensive interface change with cytoid bodies. Note the lymphocytic exocytosis.
E
Acantholytic Disorders
Pemphigus Foliaceus

Definition

• Autoimmune intraepidermal blistering condition caused by autoantibodies to desmoglein 1

Clinical features

Epidemiology

• Presents usually in fifth and sixth decades of life; endemic form arises earlier, in young adulthood and even in childhood
• No gender predilection
• Endemic form in Latin America (especially Brazil and Columbia) known as Fogo Selvagem, disease transmitted by the black fly, Simulium

Presentation

• Flaccid vesicles and bullae on noninflamed skin; usually compromised to leave only erosions and blister remnants
• Lesions typically crusted
• Positive Nikolsky sign (lateral pressure induces epidermal separation) and positive Asboe-Hansen sign (extension of blister laterally with direct pressure on blister roof)
• Often arises on trunk in seborrheic distribution (scalp, face, chest)
• Frequently displays arcuate, annular arrangement of lesions
• Oral mucosal erosions uncommon (presumably due to compensation hypothesis based upon different distribution of desmoglein 1 and 3 in mucosa versus skin)
• Pemphigus erythematosus: overlap features with lupus erythematosus, with photodistribution
• Drug-induced pemphigus foliaceus caused for example by penicillamine, captopril, and nifedipine
• UV light may trigger flare

Prognosis and treatment

• Generally benign, waxing-waning course with flares and remissions
• May be associated with thymoma or myasthenia gravis
• Topical corticosteroids may suffice in some cases
• Systemic therapy options for more severe cases include prednisone, azathioprine, mycophenolate mofetil, other immunosuppressives, minocycline, or antimalarials

Pathology

Histology

• Features may be very subtle
• Acantholysis within the granular layer with subcorneal clefting
• Roof of blister often sloughed off
• Acantholytic cells generally sparse or absent (diagnosis requires a high level of suspicion)
• Neutrophilic aggregates in the superficial epidermis
• Mild superficial perivascular mixed inflammatory infiltrate

Immunopathology/special stains

• Direct immunofluorescence: IgG, C3 in an intercellular pattern around keratinocytes of the epidermis, yielding a “chicken wire”–pattern appearance, with heavier density in the upper epidermis
• Indirect immunofluorescence: circulating antibodies directed against desmoglein 1

Main differential diagnoses

• Paraneoplastic pemphigus
• IgA pemphigus
• Bullous impetigo
• Staphylococcal scalded skin syndrome
• Subcorneal pustular dermatosis

Fig 1 Pemphigus foliaceus. Thin erythematous scaly papules and plaques on the trunk without obvious vesicles or bullae.


Fig 2 Pemphigus foliaceus. Brown, crusted papules and plaques with an erythematous base, mimicking seborrheic keratoses. (From the collection of the late NP Smith, MD; the Institute of Pathology, London.)

Fig 3 Pemphigus foliaceus. Low-power view showing separation between the stratum corneum and epidermis.

Fig 4 Pemphigus foliaceus. High-power view showing degenerate acantholytic cells and one or two neutrophils.

Fig 5 Pemphigus foliaceus. The roof is not present. The presence of a neutrophil-rich infiltrate could be misinterpreted as implying an infections condition.

Fig 6 Pemphigus foliaceus. High-power view of Figure 5 showing acantholysis.

Fig 7 Pemphigus foliaceus. Intercellular IgG deposition on direct immunofluorescence.
Pemphigus Erythematosus

Definition

• Autoimmune disorder with combined features of pemphigus foliaceus and lupus erythematosus; also known as Senear-Usher syndrome

Clinical features

Epidemiology

• Typically occurs in adults, rare in children
• Slight female predilection
• Occurs worldwide
• Associated with certain medications: penicillamine, beta-blockers, angiotensin-converting enzyme inhibitors
• May follow diagnosis of thymoma

Presentation

• Erythematous, superficial, crusted, scaly lesions
• Vesicles transient, flaccid, may not be evident
• Photodistribution: scalp, face, neck, and upper chest
• “Butterfly” pattern on cheeks
• Mucous membranes typically spared
• Very occasional development of clinical systemic lupus erythematosus

Prognosis and treatment

• Generally mild disease, responds well to treatment
• Treatment: topical corticosteroids, systemic steroids, dapsone, azathioprine, intravenous immunoglobulin

Pathology

Histology

• See pemphigus foliaceous (the features are identical)

Immunopathology/special stains

• Direct immunofluorescence:
• IgG and C3 intercellular in epidermis
• IgG and C3 along basement membrane zone

Main differential diagnoses

• Pemphigus foliaceus
• Staphylococcal scalded skin syndrome
• Bullous impetigo
• Subcorneal pustular dermatosis

Fig 1 Pemphigus erythematosus. Hyperpigmented, keratotic plaque with central bulla and erosion on the shoulder. Note other lesions of cutaneous lupus in the background.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Pemphigus erythematosus. Same patient as in Figure 1 with eroded and crusted hyperpigmented plaques associated with alopecia on the scalp.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 3 Pemphigus erythematosus. Biopsy from the patient showing a subcorneal cleft containing acantholytic cells. This pattern is identical to that seen in pemphigus foliaceus. The patient also had a positive ANA titer.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)
IgA Pemphigus

Definition

• Autoimmune intraepidermal blistering disorder mediated by IgA directed against transepidermal antigens; also known as intraepidermal IgA pustulosis, intercellular IgA dermatosis, or IgA herpetiform pemphigus

Clinical features

Epidemiology

• Newly described
• Data regarding race, sex predilection not yet established
• Reported in Asia, South America, North America, and Europe
• Average age onset in sixth decade, although all ages may be affected
• Two subtypes:
• Subcorneal pustular dermatosis (SPD) variant: antigen is desmocollin-1
• Intraepidermal neutrophilic IgA dermatosis (IEN) variant: antigen is desmoglein 1 or desmoglein 3

Presentation

• Pruritus
• SPD variant: flaccid blisters, pustules, erosion on head/neck, trunk, proximal extremities, intertriginous areas
• IEN variant: pustules, crusted erosions with vesicles at edge; vesicles may be grouped in herpetiform pattern
• Mucous membranes spared

Prognosis and treatment

• Most patients respond well to treatment
• Reports of associated IgA gammopathy, bronchial carcinoma
• Treatment with systemic corticosteroids, dapsone

Pathology

Histology

• SPD variant: subcorneal blister containing neutrophils
• IEN variant: blister at all levels of epidermis above basal layer, including follicular extension; eosinophils may be present
• Variable degrees of acantholysis
• Perivascular infiltrate of neutrophils, lymphocytes, eosinophils
• May see neutrophilic microabscesses in dermal papillae

Immunopathology/special stains

• Direct immunofluorescence demonstrates intercellular IgA; preferential binding depending on subtype:
• SPD variant: upper epidermis
• IEN: lower epidermis
• PAS and Gram stains to rule out infectious process

Main differential diagnoses

• Sneddon-Wilkinson disease
• Pustular psoriasis
• Pustular drug eruption
• Pemphigus vulgaris
• Pemphigus foliaceous
• Candidiasis
• Impetigo

Fig 1 IgA pemphigus. Erosions and vesicopustules on an erythematous base involving the buttock.

Fig 2 IgA pemphigus. Intraepidermal blister showing acantholysis and conspicuous eosinophils.

Fig 3 IgA pemphigus. High-power view of Figure 2 .
Pemphigus Vulgaris

Definition

• Autoimmune intraepidermal blistering condition

Clinical features

Epidemiology

• Age 40s to 50s, although children and elderly also can be affected
• Gender ratio equal
• No clear racial preference
• Drug-induced cases often triggered by captopril, penicillamine

Presentation

• Flaccid vesicles, bullae, and erosions on noninflamed skin
• May be painful, occasionally pruritic
• Positive Nikolsky sign (lateral pressure induces epidermal separation)
• Often symmetrically distributed
• Pemphigus vegetans variant with thickened, vegetating, moist, irregularly surfaced plaques, typically in intertriginous areas or face
• Mucosal erosions in nearly all patients, oral involvement often the presenting feature
• May affect conjunctiva and internal mucosae, esophagus, or vagina

Prognosis and treatment

• Prior to use of corticosteroids, prognosis grave
• Immunosuppressives (e.g., prednisone, azathioprine, mycophenolate mofetil)
• Intravenous immunoglobulin, rituximab, and biologic agents also options

Pathology

Histology

• Intraepidermal clefting or vesiculation
• Suprabasal acantholysis conferring tombstone appearance
• Follicular involvement (compare with Hailey-Hailey disease)
• Mild superficial perivascular mixed inflammatory infiltrate often with eosinophils
• Early stages may present as eosinophilic spongiosis
• Pemphigus vegetans—marked, sometimes pseudoepitheliomatous epidermal hyperplasia, acantholysis may be very focal and difficult to find, eosinophilic spongiosis

Immunopathology/special stains

• Direct immunofluorescence: IgG, C3 in an intercellular pattern around keratinocytes of the epidermis, yielding a “chicken wire”–pattern appearance
• Indirect immunofluorescence: circulating antibodies directed against intercellular antigens
• Antibodies react with desmosomal proteins desmoglein 3 (exclusively in oral disease) and desmoglein 1 (combined with desmoglein 3 in cutaneous disease)
• Pemphigus vegetans: desmoglein 3

Main differential diagnoses

• Other variants of pemphigus
• Hailey-Hailey disease
• Darier’s disease
• Grover’s disease
• Acantholytic acanthoma
• Focal acantholytic dyskeratosis (if acantholysis predominates)

Fig 1 Pemphigus vulgaris. Eroded and crusted plaques and flaccid vesicles with erythematous base on the back.

Fig 2 Pemphigus vulgaris. Hemorrhagic ulcers on the soft palate.


Fig 3 Pemphigus vulgaris. This is a biopsy of the base of a blister. Note the epithelial-lined villi projecting from the basal layer of the epidermis.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 4 Pemphigus vulgaris. High-power view showing the tombstone effect and acantholysis.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 5 Pemphigus vulgaris. This is an example of an oral lesion showing suprabasilar blistering.

Fig 6 Pemphigus vulgaris. There is suprabasilar acantholysis and a well-developed tombstone effect.

Fig 7 Pemphigus vulgaris. A perivascular lymphocytic infiltrate is present. No eosinophils are seen.

Fig 8 Pemphigus vulgaris. Direct immunofluorescence showing intercellular C3 deposition between keratinocytes, with heavy staining of the lower epidermis.
Pemphigus Vegetans

Definition

• Variant of pemphigus vulgaris with characteristic moist vegetative appearance

Clinical features

Epidemiology

• Affects adults, slightly earlier age than traditional pemphigus vulgaris
• Female predilection

Presentation

• Flaccid vesiculobullae and moist erosions with crusting, weeping
• With healing, granulation tissue leads to hypertrophic scars, leaving an irregular, warty, “vegetative” surface
• Plaques distributed over face, scalp, intertriginous areas
• Neumann type: more severe, vegetative plaques prominent, may see cerebriform tongue
• Hallopeau type: milder, features pustules in the early stages
• Oral involvement variable: mouth, esophagus

Prognosis and treatment

• Hallopeau type: good prognosis, responsive to topical and/or systemic immunosuppressive therapy (e.g., corticosteroids, dapsone), may resolve spontaneously
• Neumann type: worse prognosis, more difficult to treat

Pathology

Histology

• Acanthosis often pseudoepitheliomatous
• Eosinophilic spongiosis with intraepidermal eosinophilic microabscesses
• Subtle suprabasal acantholysis
• Dermal chronic inflammatory cell infiltrate with eosinophils

Immunopathology/special stains

• Direct immunofluorescence: intercellular deposition of IgG, C3
• Indirect immunofluorescence: circulating antibodies to intercellular desmoglein 3
• Variable antibodies to desmocollins 1 and 2

Main differential diagnoses

• Pemphigus vulgaris
• Infections with pseudoepitheliomatous hyperplasia
• Halogenoderma
• Pyostomatitis vegetans (oral equivalent)

Fig 1 Pemphigus vegetans. There is epidermal hyperplasia and intraepidermal eosinophil-rich microabscesses.

Fig 2 Pemphigus vegetans. Acantholytic keratinocytes are present within the microabscesses.
Paraneoplastic Pemphigus

Definition

• Autoimmune blistering condition associated with internal malignancy and characterized by autoantibodies to both desmosomal and hemidesmosomal antigens; probably a heterogeneous entity

Clinical features

Epidemiology

• Predisposing malignancy, particularly lymphoproliferative disorders, such as non-Hodgkin lymphoma, also carcinomas
• Usually adults affected, often in seventh decade of life, although may also occur in children (associated with Castleman’s disease)
• No clear racial predilection
• No gender predilection

Presentation

• Painful oral erosions covering any portion of the oropharynx characteristic
• Spectrum of skin morphologies seen, often beginning with macular erythema, with subsequent denudation and positive Nikolsky sign
• Flaccid vesicles and bullae distributed over trunk, extremities
• Associated lichenoid small erythematous to brownish papules coalescent into larger scaling plaques
• Ocular involvement (conjunctivitis, symblepharon) common
• Lesions tend to be painful
• Internal malignancy seen in vast majority of cases, most commonly lymphoproliferative (non-Hodgkin’s lymphoma, chronic lymphocytic leukemia), but also other conditions including Castleman’s disease, Waldenström’s macroglobulinemia, thymoma, sarcoma, or lung carcinoma
• Bronchiolitis obliterans is a major pulmonary complication

Prognosis and treatment

• Poor prognosis overall, with high mortality (approximately 90%) from sepsis and multiorgan failure linked to underlying malignancy
• Mucocutaneous findings correlate variably with internal malignancy
• Treatment of internal malignancy in some cases appears to improve paraneoplastic pemphigus
• Topical dressings and measures to minimize infection and allow healing
• Various therapeutic options, including immunosuppressive agents (corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil), plasmapheresis, intravenous immunoglobulin, rituximab, and stem cell transplant all used

Pathology

Histology

• Suprabasal acantholysis with dyskeratosis, lymphocytic exocytosis
• Variable epidermal necrosis and spongiosis
• Basal vacuolar interface change
• Accompanying lichenoid, predominantly lymphocytic infiltrate may be prominent
• Papillary dermal melanophages often seen

Immunopathology/special stains

• Direct immunofluorescence: IgG (often also IgA, IgM) and C3 located in intercellular pattern between keratinocytes and along dermal–epidermal junction in granular or linear fashion
• Indirect immunofluorescence (rat bladder epithelium): circulating autoantibodies affix to substrate arranged in intercellular and basement membrane zone pattern
• By immunoprecipitation or immunoblotting methods; autoantibodies detected against desmoglein 1, desmoglein 3, envoplakin (210 kd), periplakin (190 kd), desmoplakin 1 (250 kd), desmoplakin 2 (210 kd), BP antigen 1 (230 kd), and plectin

Main differential diagnoses

• Adverse drug reaction
• Pemphigus vulgaris
• Erythema multiforme
• Stevens-Johnson syndrome/toxic epidermal necrolysis
• Lichen planus

Fig 1 Paraneoplastic pemphigus. Extensive hemorrhagic ulcers on the lips, tongue, and posterior pharynx.
(Courtesy of M Avram, MD; Harvard Medical School, Boston.)


Fig 2 Parareoplastic pemphigus. Low-power view showing suprabasal acantholysis and interface change.

Fig 3 Parareoplastic pemphigus. Higher-power view showing suprabasal cleft.

Fig 4 Parareoplastic pemphigus. Basal cell hydropic degeneration with cytoid bodies and an upper dermal lymphohistiocytic infiltrate.

Fig 5 Paraneoplastic pemphigus. High-power view showing interface change, apoptosis, and a dense lymphohistiocytic infiltrate.
Darier’s Disease (Keratosis Follicularis)

Definition

• Genodermatosis characterized by coalescent papules with greasy scale in seborrheic distribution caused by mutation (ATP2A2) in calcium channel pump of sarcoplasmic reticulum (SERCA2 protein)

Clinical features

Epidemiology

• Autosomal dominant
• Usually presents in late childhood to early adulthood
• No clear gender predilection

Presentation

• Brownish, erythematous, 2- to 5-mm keratotic papules coalescent into ill-defined, irregular plaques with greasy scale
• Distributed in seborrheic regions, involving central chest in V -shape, scalp, central face, intertriginous areas
• Palmar pits common
• Exacerbated by heat, sunlight, certain medications (e.g., oral corticosteroids, lithium)
• Superinfection may contribute to malodor
• Hypertrophic variant with vegetative, thick plaques
• Vesicobullous variant with generally flaccid blisters
• Fingernail changes characteristic, including longitudinal red/white bands, longitudinal ridging, and pathognomonic distal V -shaped nick
• Cobblestoning of the oral and sometimes anogenital mucosae composed of white papules alternating with depressions

Prognosis and treatment

• Chronic, unremitting course, punctuated by flares
• Increased susceptibility to infections, including bacterial and viral (e.g., herpetic)
• Psychological toll
• Management requires judicious avoidance of exacerbating factors (e.g., excessive sunlight, heat)
• Topical corticosteroids, topical keratolytics, topical 5-fluorouracil may be helpful
• Antibiotics as indicated for superinfection
• Systemic retinoids mainstay of therapy for many patients
• Surgical modalities, including dermabrasion, laser, as well as photodynamic therapy also tried

Pathology

Histology

• Suprabasilar acantholysis with dyskeratosis
• Corps ronds (dyskeratotic keratinocytes with eccentric round nucleus surrounded by clear halo and eosinophilic cytoplasm) within spinous or granular layers
• Corps grains (smaller, oval eosinophilic cells with dark, blunt-ended, cigar-shaped nuclei) within parakeratotic stratum corneum

Immunopathology/special stains

• Direct immunofluorescence studies negative
• Indirect immunofluorescence studies negative

Main differential diagnoses

• Pemphigus vulgaris
• Hailey-Hailey disease
• Warty dyskeratoma
• Grover’s disease

Fig 1 Darier’s disease. Crusted, hyperkeratotic, and hemorrhagic plaques on the mid lower back.
(Courtesy of B Kockentiet, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Darier’s disease. Hyperkeratosis, central parakeratosis with grains and corps ronds. Note the suprabasal acantholysis.
Hailey-Hailey Disease (Familial Benign Pemphigus)

Definition

• Inherited skin condition of pruritic moist intertriginous plaques caused by calcium channel pump mutation (ATP2C1) and characterized by widespread acantholysis

Clinical features

Epidemiology

• Autosomal dominantly inherited
• No gender predominance
• Lesions usually noticed during teenage years, but may not become symptomatic until fourth or fifth decades of life

Presentation

• Intertriginous moist pruritic erythematous to brown, warty, scaly, irregular plaques, sometimes with overlying vesicles
• Symmetrically distributed, usually involving, the axillary, groin, genital, perianal, chest, and neck regions
• Superinfection by bacteria and/or fungi leads to malodor
• Patients may complain of itching, burning, stinging sensations
• Exacerbated by friction, heat, and infection

Prognosis and treatment

• Minimization of heat, friction
• As no clear optimal, effective treatment currently exists, a number of therapies are used, including topical and systemic corticosteroids, topical and systemic retinoids, topical calcineurin inhibitors, methotrexate, dapsone, antibiotics
• Surgical modalities include dermabrasion, laser therapy

Pathology

Histology

• Acantholysis of the full-thickness of an acanthotic epidermis, resembling a “dilapidated brick wall”
• Villae projecting into lacunae may be present
• Usual absence of adnexal involvement (compare with pemphigus vulgaris)
• Associated variable patchy acute or chronic inflammatory cell infiltrate

Immunopathology/special stains

• Direct immunofluorescence studies negative
• Indirect immunofluorescence studies negative

Main differential diagnoses

• Darier’s disease
• Pemphigus vulgaris
• Grover’s disease

Fig 1 Hailey-Hailey disease. Scattered few-millimeter erosions on the perianal and perineal regions.

Fig 2 Hailey-Hailey disease. Discrete few-millimeter erosions are distributed over the left inguinal and proximal inner thigh.



Fig 3 Hailey-Hailey disease. Acute onset erythematous plaque with incipient vesicles in the inframammary fold.

Fig 4 Hailey-Hailey disease. At the edge of the lesion, there is hyperkeratosis, parakeratosis, and acanthosis. Note the acantholysis and projecting dermal papillae covered by a thin layer of residual basal keratinocytes.

Fig 5 Hailey-Hailey disease. High-power view showing the characteristic dilapidated brick wall appearance.

Fig 6 Hailey-Hailey disease. This is a biopsy from a dark-skinned patient showing early acantholysis. Note the pigment incontinence.
(Courtesy of I Chaudhry, MD; Medi-Link Consultancy, Timperley, UK.)
Grover’s Disease (Transient Acantholytic Dermatosis)

Definition

• Idiopathic pruritic dermatosis classically of the trunk in middle-aged men, with histology characterized by acantholysis and/or spongiosis

Clinical features

Epidemiology

• Adult to older men; females much less often affected
• White predilection

Presentation

• Few-millimeter discrete keratotic erythematous papule comprises most common primary lesion
• Pustules, vesicles, and bullae also described
• Distributed over back and trunk, particularly the chest and upper back
• Mucosae typically unaffected
• Can number up to over 100 individual lesions
• Pruritus common
• Exacerbation with heat and sweating

Prognosis and treatment

• Usually lasts few weeks to months, but despite original naming (“transient”); may be chronic and recurrent
• Avoidance of excessive heat and sweating may help
• Topical corticosteroids most commonly used
• Phototherapy, retinoids, and methotrexate tried in more severe or refractory cases

Pathology

Histology

• Five different patterns recognized: spongiotic, Darier-like, Hailey-Hailey–like, pemphigus vulgaris–like, pemphigus foliaceus–like
• Spongiotic variant: epidermal spongiosis, superficial mild perivascular chronic inflammatory infiltrate
• Darier-like: acantholysis with dyskeratosis, including corps ronds and grains
• Hailey-Hailey: full-thickness epidermal acantholysis resulting in epidermal disintegration resembling “dilapidated brick wall”
• Pemphigus vulgaris–like: suprabasilar acantholysis with “tombstone” appearance
• Pemphigus foliaceus–like: subcorneal acantholysis and clefting
• Clue to Grover’s disease is the presence of more than one of the above patterns in the same skin biopsy

Immunopathology/special stains

• Immunofluorescence negative

Main differential diagnoses

• Eczematous dermatitis
• Darier’s disease
• Hailey-Hailey disease
• Pemphigus vulgaris
• Pemphigus foliaceus
• Acantholytic actinic keratosis
• Focal acantholytic dyskeratosis

Fig 1 Grover’s disease. Erythematous nonfollicular small papules on the trunk.

Fig 2 Grover’s disease. Low-power view showing an intraepidermal vesicle.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 3 Grover’s disease. Focal acantholysis is seen along the floor of the vesicle.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)



Fig 4 Grover’s disease. Elsewhere in the biopsy the features are reminiscent of Darier’s disease, note the corps ronds.
(Courtesy of D Whittemore, DO; University of Texas, Houston.)

Fig 5 Grover’s disease. Low-power view showing another case with multifocal epidermal lesion and massive hyperkeratosis.

Fig 6 Grover’s disease. Higher-power view of Figure 5.

Fig 7 Grover’s disease. Suprabasilar and intraepidermal acantholysis with numerous corps ronds and grains.

Fig 8 Grover’s disease. Higher-power view of Figure 7 showing the numerous acantholytic cells.

Fig 9 Grover’s disease. Higher-power view showing acantholytic and dyskeratotic cells with corps ronds and grains.
F
Subepidermal Vesicular Dermatitis
Bullous Pemphigoid

Definition

• Immunobullous subepidermal blistering condition

Clinical features

Epidemiology

• Condition of adulthood and elderly
• Rare childhood cases, sometimes associated with previous vaccination
• Occasionally drug-related

Presentation

• Pruritic tense bullae without classic Nikolsky sign
• Distributed over abdomen, inner thighs, and flexural aspects of the limbs
• May exhibit preceding “prebullous pemphigoid” erythematous and/or urticarial phase manifesting as pruritic pink-erythematous wheals

Prognosis and treatment

• Often slowly progressive, although most patients experience remission with treatment
• Treatment options include prednisone, other immunosuppressive agents (e.g., azathioprine, mycophenolate), tetracycline, or biologic agents (rituximab)
• Overall mortality approximately 10%, largely as a consequence of immunotherapy

Pathology

Histology

• Prebullous lesions characterized by edema, perivascular eosinophilic infiltrate, eosinophilic spongiosis
• Subepidermal blister
• Preservation of dermal papillae (festooning)
• Eosinophil-rich infiltrate in blister cavity
• Eosinophils aligned along the dermal–epidermal junction
• Superficial perivascular lymphohistiocytic infiltrate with conspicuous eosinophils
• Eosinophil dermal papillary abscesses occasionally seen
• Cell-poor/-free variant

Immunopathology/special stains

• Linear C3 and IgG along the dermal–epidermal junction (90%) on direct immunofluorescence
• C3 is typically the stronger immunoreactant
• Circulating antibasement membrane antibodies (75%-90%)
• By indirect split-skin immunofluorescence, immunoreactants localized to the roof of the blister
• BPag1 (230 kD) and BPag2 (180 kD) antigens

Main differential diagnoses

• Cell-rich variants
• Dermatitis herpetiformis
• Linear IgA disease
• Inflammatory epidermolysis bullosa acquisita
• Bullous insect-bite reaction
• Mucosal pemphigoid
• Cell-poor variants
• Mucosal pemphigoid
• Epidermolysis bullosa congenita
• Epidermolysis bullosa acquisita
• Porphyria cutanea tarda
• Pseudoporphyria

Fig 1 Bullous pemphigoid. Numerous various-sized, tense, variably hemorrhagic, vesicobullae on the trunk of an elderly man.

Fig 2 Bullous pemphigoid. Prebullous lesion showing eosinophilic spongiosis, dermal edema, and an intense perivascular and interstitial eosinophil-rich infiltrate.



Fig 3 Bullous pemphigoid. Established dome-shaped unilocular blister. Note the intact roof.

Fig 4 Bullous pemphigoid. The blister cavity contains edema fluid, fibrin, and a mixed inflammatory cell infiltrate with conspicuous eosinophils.

Fig 5 Bullous pemphigoid. Preservation of the dermal papillae along the floor of the blister cavity is typical of bullous pemphigoid.

Fig 6 Bullous pemphigoid. In this field, there is a perivascular lymphohistiocytic infiltrate with prominent eosinophils.

Fig 7 Bullous pemphigoid. Dermal papillary eosinophil microabscesses are sometimes a feature, particularly in prebullous lesions.

Fig 8 Bullous pemphigoid. Direct immunofluorescence showing linear IgG along the dermal–epidermal junction.
Pemphigoid (Herpes) Gestationis

Definition

• Very rare pregnancy-associated autoimmune bullous dermatosis, with antibodies to the hemidesmosomal protein BPag2; very similar clinically and pathologically to bullous pemphigoid. Previously known as herpes gestationis.

Clinical features

Epidemiology

• Third trimesters of primiparous women
• May affect succeeding pregnancies
• More common in whites (may be reflection of HLA association)

Presentation

• Pruritic urticarial erythematous, edematous few-millimeter papules coalescent into larger plaques
• Generally symmetrically distributed over periumbilical abdomen, trunk
• Vesiculobullous lesions arise on erythematous background
• May subside or flare with delivery

Prognosis and treatment

• Associated with increased risk of premature delivery, and transient neonatal involvement may occur; otherwise, no statistically significant other morbidity to fetus
• Association in mother with autoimmune conditions (thyroid disease, pernicious anemia)
• Therapy with systemic corticosteroids or other steroid-sparing immunosuppressives (e.g., cyclosporine)
• Risk of recurrence in subsequent pregnancies

Pathology

Histology

• Subepidermal clefting or tense blister with eosinophils at the base
• Superficial perivascular chronic inflammatory infiltrate with scattered eosinophils
• Papillary dermal edema

Immunopathology/special Stains

• Direct immunofluorescence: C3 and to a lesser extent IgG deposition along dermal–epidermal junction
• Indirect immunofluorescence usually positive for circulating antibodies to basement membrane region, localizing to roof on salt-split skin substrate

Main differential diagnoses

• Bullous pemphigoid
• Inflammatory epidermolysis bullosa acquisita
• Linear IgA disease
• Drug hypersensitivity reaction
• PUPPP (pruritic urticarial papules and plaques of pregnancy)

Fig 1 Pemphigoid gestationis. Edematous, erythematous periumbilical plaque in a pregnant woman.
(Courtesy of E Calonje, MD; St John’s Institute of Dermatology, London.)

Fig 2 Pemphigoid gestationis. A dozen or so annular erythematous, edematous few-millimeter papules to over one-centimeter plaques scattered over the right thigh, knee, and calf.

Fig 3 Pemphigoid gestationis. Low-power view of an early lesion showing papillary dermal edema and a superficial dermal inflammatory cell infiltrate.



Fig 4 Pemphigoid gestationis. Small subepidermal eosinophil-rich blister.

Fig 5 Pemphigoid gestationis. High-power view showing massive dermal edema.

Fig 6 Pemphigoid gestationis. The dermal infiltrate contains numerous eosinophils.

Fig 7 Pemphigoid gestationis. There is striking linear C3 deposition along the dermal–epidermal junction.
Mucosal (Cicatricial) Pemphigoid

Definition

• Autoimmune mucocutaneous blistering disease; also known as benign mucous membrane pemphigoid, ocular pemphigoid, or cicatrical pemphigoid

Clinical features

Epidemiology

• Uncommon
• Disease of older patients, average onset in seventh decade
• Female predilection (female to male ratio 2:1)
• Brunsting-Perry variant male predominance (female to male ratio 1:2)
• Heterogeneous disease with several target antigens:
• BPag2 and BPag1
• Laminin 5 (epiligrin) and 6
• β 4 integrin
• May occur secondary to medications: clonidine, D-penicillamine

Presentation

• Oral lesions occur in over 3 4 of patients
• Desquamative gingivitis most common
• Ragged ulcers and erosions on gingiva, palate, buccal mucosa; scarring rare
• Ocular lesions occur in 2 3 of patients
• Conjunctiva commonly involved
• Ocular dryness and keratinization
• Corneal erosions
• Ectropion, symbelpharon (fibrous bands/adhesions)
• Eye disease may be sole manifestation of disease
• Skin lesions in 1 3 of patients:
• Erosions, tense blisters with background fibrosis, milia
• Pruritus, burning
• On scalp may lead to alopecia
• May also involve larynx, genital area, esophagus, nasopharynx
• Brunsting-Perry variant
• Localized to scalp, forehead, cheeks, and neck
• Expanding erythematous plaques with central scarring and vesicles/bullae at edge and within center of lesions

Prognosis and treatment

• Chronic, progressive disease with significant scarring
• Ocular disease sometimes leads to blindness
• Laryngeal involvement can result in obstruction and asphyxiation
• Disease may remit and relapse
• Treatment:
• Topical corticosteroids, systemic steroids, steroid sparring agents, cyclophosphamide for severe ocular, laryngeal disease
• Tracheostomy for laryngeal disease/may be recalcitrant to treatment

Pathology

Histology

• Oral lesions:
• Nonspecific ulcer with chronic inflammation
• May see subepithelial cleft with mixed inflammation in lamina propria
• Cutaneous lesions:
• Subepidermal blister with fibrin, edema, inflammatory cells in blister cavity
• Variable degrees of inflammation in dermis: lymphocytes and histiocytes with admixed plasma cells, eosinophils, neutrophils
• May be cell poor/free
• Dermal fibrosis in longstanding lesions

Immunopathology/special stains

• Direct immunofluorescence:
• Linear IgG, C3 along basement membrane zone
• May also see IgA
• Salt-split studies: epidermal and dermal localization depending on antigen targeted
• Indirect immunofluorescence:
• Low titers
• Positive in less than 1 3 of patients

Main differential diagnoses

• Bullous pemphigoid
• Epidermolysis bullosa acquisita
• Linear IgA disease

Fig 1 Mucosal pemphigoid. Note the intense erythema with erosion, features of desquamative gingivitis.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Mucosal pemphigoid. There is a subepidermal blister containing eosinophils and lymphocytes.


Fig 3 Mucosal pemphigoid. Note the perivascular and interstitial infiltrate of lymphocytes, histiocytes, and conspicuous eosinophils.

Fig 4 Mucosal pemphigoid. Low-power view of oral lesion.

Fig 5 Mucosal pemphigoid. High-power view of blister cavity shown in Figure 4 .

Fig 6 Mucosal pemphigoid. There is perivascular and interstitial lymphohistiocytic infiltrate with occasional plasma cells.

Fig 7 Mucosal pemphigoid. Biopsy specimen of an early oral lesion showing a cell-free subepidermal cleft.

Fig 8 Mucosal pemphigoid. Strong linear C3 deposition along the dermal–epidermal junction.
Epidermolysis Bullosa Acquisita

Definition

• Autoimmune blistering disease caused by antibodies to the globular carboxyl terminus of collagen type VII

Clinical features

Epidemiology

• Very rare condition
• No clear racial predilection
• No clear gender predilection
• Arises in adulthood and the elderly, rare reports in children

Presentation

• Subepidermal blistering condition that may present as a localized noninflammatory (classic) variant, as a generalized inflammatory variant, and as a mucosal variant
• Localized noninflammatory lesions commonly involve the areas of the body subject to trauma (e.g., hands, elbows, knees, buttocks): individual skin lesions usually asymptomatic, consist of tense vesicles and bullae, or as blister remnant erosions or ulceration
• Localized variant often associated with milia and nail dystrophy or nail loss
• In the generalized inflammatory variant, lesions are typically widespread and resemble bullous pemphigoid or less often dermatitis herpetiformis; mucosal lesions important cause of morbidity
• Mucosal variant resembling mucosal pemphigoid
• Association with inflammatory bowel disease

Prognosis and treatment

• Generally unresponsive to traditional treatments for bullous pemphigoid
• Complicated by scarring on skin and mucosal surfaces
• Systemic corticosteroids, other antiimmunosuppressives used with variable response

Pathology

Histology

• Cell-free variant
• Blister cavity often appears empty or contains erythrocytes
• Festooning generally marked
• Dermal scarring and milia
• Basement membrane lies along the roof of the blister
• Inflammatory variant
• May resemble dermatitis herpetiformis or less often bullous pemphigoid

Immunopathology/special stains

• Direct immunofluorescence: C3 and IgG along dermal–epidermal junction in a linear pattern
• Indirect immunofluorescence: localizes target immunoreactants to the base (dermal side) of salt-split skin
• Linear IgA variant
• Immunoreactants localize to the anchoring fibrils at the epidermal basement membrane

Main differential diagnoses

• Cell-free variant
• Epidermolysis bullosa congenita
• Porphyria cutanea tarda
• Pseudoporphyria
• Cell-free mucosal pemphigoid
• Bullous amyloidosis
• Inflammatory variants
• Bullous pemphigoid
• Dermatitis herpetiformis
• Linear IgA disease
• Bullous systemic lupus erythematosus
• Mucosal pemphigoid

Fig 1 Epidermolysis bullosa acquisita. Erythematous vesicle on the trunk.

Fig 2 Epidermolysis bullosa acquisita. Discrete ulcer on the lower lip mucosa with a vesicle on the adjacent skin.


Fig 3 Epidermolysis bullosa acquisita. Classic variant showing a cell-free subepidermal blister. Note the preservation of the dermal papillae.

Fig 4 Inflammatory epidermolysis bullosa acquisita. There is a subepidermal blister containing edema fluid and inflammatory cells.

Fig 5 Inflammatory epidermolysis bullosa acquisita. High-power view showing numerous eosinophils in this bullous pemphigoid–like example.

Fig 6 Epidermolysis bullosa acquisita. Thick band of linear IgG along the dermal side of a salt-split direct immunofluorescence study.
Epidermolysis Bullosa Congenita

Definition

• Heterogeneous group of inherited congenital blistering conditions, each form associated with a specific gene encoding a protein component of the molecular framework of the dermal–epidermal junctional region

Clinical features

Epidemiology

• Epidermolysis bullosa simplex (EBS) : mutation in keratins 5 and 14; autosomal dominant inheritance
• Hemidesmosomal epidermolysis bullosa (HEB) : mutations in BP180, plectin, α6β4 integrin; autosomal recessive inheritance
• Junctional epidermolysis bullosa (JEB) : mutation in laminin 5; autosomal recessive inheritance
• Dystrophic epidermolysis bullosa (DEB) : mutation in collagen VII; autosomal dominant or autosomal recessive inheritance

Presentation

• Broadly classified into four major categories, each with a distinctive level of blistering: simplex, hemidesmosomal, junctional, and dystrophic
• Blistering particularly at sites of trauma (e.g., hands, feet, elbows, diaper area)
• Nails, hair, and teeth may be variably involved
• Systemic involvement sometimes evident: gastrointestinal, respiratory
• EBS : defect in the basal layer of the epidermis causes peeling skin noted usually at birth; fragile skin through life. Weber-Cockayne variant most common. Induced by trauma; palms and soles usually affected.
• HEB : mixed group includes cases associated with pyloric atresia and late-onset muscular dystrophy
• JEB : Herlitz (letalis) type and non-Herlitz types
• DEB : may be severe, with scarring and increased risk of squamous cell carcinoma (Hallopeau-Siemens)

Prognosis and treatment

• Concern for contractures, scarring, infection, disfigurement in junctional or dystrophic forms
• Sepsis important cause of death in infancy
• High incidence of squamous cell carcinoma in recessive dystrophic variant; important cause of death later in life
• Local wound care, physical therapy, possible gene therapy on the horizon

Pathology

Histology

• EBS : split within the lower epidermis associated with irregular keratin clumps (Dowling-Meara), cytolysis seen in prebullous lesions
• HEB : split within hemidesmosome
• JEB : split within the lamina lucida
• DEB : split deep to the lamina densa
• Features may be subtle
• Generally noninflammatory blisters, cannot distinguish subtypes on the basis of simple histology
• Squamous carcinomas in recessive dystrophic patients typically are deceptively well differentiated
• Dermis with minimal or no inflammation; scarring and milia sometimes evident

Immunopathology/special stains

• Immunohistochemistry for laminin or type IV collagen may be helpful: if immunoreactant is present at the base of blister, then compatible with EBS, HEB, or JEB; if present in the roof of blister, then compatible with DEB
• Precise diagnosis and subtype often dependent upon electron microscopy and immunoelectron microscopy

Main differential diagnoses

• Cell-free bullous pemphigoid
• Porphyria cutanea tarda
• Pseudoporphyria
• Epidermolysis bullosa acquisita
• Bullous disease of renal failure
• Bullous amyloidosis

Fig 1 Hemidesmosomal epidermolysis bullosa. There is extensive skin loss in this fetus. Pyloric atresia was found at autopsy.

Fig 2 Junctional epidermolysis bullosa. Scarring, variegated pigmentation with old blisters on the feet.


Fig 3 Recessive dystrophic epidermolysis bullosa. This patient has developed a squamous cell carcinoma on the knee.

Fig 4 Epidermolysis bullosa simplex. Low-power view showing intraepidermal separation on acral skin in a patient with epidermolysis bullosa simplex, Weber-Cockayne variant.
(Courtesy of F McMullen, MD; Virginia Commonwealth University, Richmond.)

Fig 5 Epidermolysis bullosa simplex. Higher-power view showing separation within mid epidermis.
(Courtesy of F McMullen, MD; Virginia Commonwealth University, Richmond.)

Fig 6 Epidermolysis bullosa simplex. Transition zone between blister cavity and cytolytic epidermal cells.
(Courtesy of F McMullen, MD; Virginia Commonwealth University, Richmond.)

Fig 7 Hemidesmosomal epidermolysis bullosa. There is a cell-free subepidermal blister. Note the primitive dermal mesenchymal tissue.

Fig 8 Recessive dystrophic epidermolysis bullosa. There is a cell-free subepidermal blister with dermal scarring. Squamous cell carcinoma is evident in the upper left field.
Dermatitis Herpetiformis

Definition

• Subepidermal neutrophil-rich blistering disorder associated with celiac disease

Clinical features

Epidemiology

• Favors whites, particularly of Northern European and Scandinavian descent, linked with HLA haplotype (particularly HLA-B8 and HLA-DR3)
• Young adults
• More commonly reported in men
• Of those patients with gluten-sensitive enteropathy, less than one quarter have dermatitis herpetiformis

Presentation

• Tense, pruritic, urticarial small (few-millimeter) papules with associated vesicles and occasionally bullae
• Distributed symmetrically over extensor surfaces of elbows, knees, buttocks, back
• Often blisters have been excoriated, leaving only crusted erosions
• Although most do not complain of symptoms of malabsorption, gluten-sensitive enteropathy detected histologically in vast majority of patients
• Triggered by gluten-containing foods (e.g., wheat, barley, rye)

Prognosis and treatment

• Lifelong course punctuated by flares and periods of remission
• Risk of development of bowel cancer, particularly gastrointestinal lymphoma
• Gluten-free diet most beneficial in terms of symptoms and in terms of reducing risk of non–Hodgkin’s lymphoma
• Neutrophil-targeted pharmacologic agents, classically dapsone (also colchicine)

Pathology

Histology

• Subepidermal blister
• Effacement of dermal papillae
• Neutrophil-rich infiltrate in blister cavity and dermis
• Karyorrhexis
• Eosinophils sometimes evident in older lesions
• Neutrophil microabscesses within edematous dermal papillae in the adjacent skin or featured in very early lesions

Immunopathology/special stains

• Direct immunofluorescence (from perilesional skin): granular IgA deposition within dermal papillae; fibrin and C3 also present
• Less commonly, linear granular IgA at epidermal–dermal junction
• Target antigen currently suspected to be epidermal transglutaminase 3
• IgA endomysial antibodies positive in majority of cases

Main differential diagnoses

• Linear IgA disease
• Bullous pemphigoid
• Bullous systemic lupus erythematosus
• Bullous drug eruption
• Epidermolysis bullosa acquisita

Fig 1 Dermatitis herpetiformis. Excoriations on the buttocks adjacent to the gluteal cleft, a characteristic site.
(Courtesy of J Nunley, MD; Virginia Commonwealth University, Richmond.)

Fig 2 Dermatitis herpetiformis. Scanning view of a subepidermal blister. A neutrophil dermal papillary microabscess is present in the adjacent skin.


Fig 3 Dermatitis herpetiformis. Medium-power view of edge of blister.

Fig 4 Dermatitis herpetiformis. Within the dermis is an intense neutrophil infiltrate. One or two eosinophils are present, a not uncommon finding in established lesions.

Fig 5 Dermatitis herpetiformis. High-power view of neutrophil microabscesses. These are not specific and may also be seen in linear IgA disease, inflammatory epidermolysis bullosa acquisita, and bullous systemic lupus erythematosus.

Fig 6 Dermatitis herpetiformis. Granular IgA and C3 are typically present in the tips of the dermal papillae on direct immunofluorescence.
Linear IgA Disease

Definition

• Autoimmune bullous dermatosis with characteristic immunopathologic profile, associated with autoantibodies to multiple basement membrane region target antigens

Clinical features

Epidemiology

• Historically, two clinical forms recognized: chronic bullous disease of childhood (CBDC) and linear IgA disease of adults
• CBDC arises in infancy or childhood, with no gender or racial predilection
• Linear IgA disease of adults arises in a wide age range
• Slight female predilection
• Drug-induced form associated with exposure to vancomycin, lithium, diclofenac, captopril, and penicillins, among others

Presentation

• Tense vesicles and bullae on erythematous base
• Arranged in classically closely set, linear or curvilinear arrangement at the periphery of annular or polycyclic plaques, resembling a “string of pearls,” or in a grouped crop, akin to a “cluster of jewels”
• Distribution in children in groin, perineal, lower abdomen areas commonly, but hands, feet, and face may also be affected
• In adults, trunk and limbs generally involved
• Variable pruritus
• Waxing and waning course for most forms
• Drug-induced linear IgA disease typically occurs within two weeks of medication exposure
• Mucosal involvement not uncommon, with involvement of oral, genital, and ocular epithelium, which may result in severe scarring
• Possible association with malignancy, particularly lymphoproliferative and autoimmune processes, including inflammatory bowel disease, lupus erythematosus, IgA nephropathy

Prognosis and treatment

• Cessation of culprit medication in drug-induced linear IgA disease is curative
• CBDC carries an overall better prognosis, with higher likelihood of remission
• Non–drug-associated linear IgA disease is a chronic condition, marked by waxing–waning course
• Commonly used therapeutic agents include dapsone, colchicine, prednisone, and intravenous immunoglobulin

Pathology

Histology

• Subepidermal neutrophil-rich blister resembling dermatitis herpetiformis most commonly seen
• May sometimes be eosinophil-rich and resemble bullous pemphigoid
• Eosinophilic spongiosis is an occasional feature
• Split is through lamina lucida or deep to the lamina densa

Immunopathology/special stains

• Direct immunofluorescence:
• IgA deposited in linear fashion along the dermal–epidermal junction
• Other immunoreactants such as C3, IgG, and IgM may also be detected
• Indirect immunofluorescence: circulating IgA antibasement membrane antibody in 30% of cases
• Split skin may label epidermal, dermal, or both sides
• Multiple basement membrane target constituents including bullous pemphigoid antigens and type VII collagen

Main differential diagnoses

• Dermatitis herpetiformis
• Epidermolysis bullosa acquisita
• Bullous pemphigoid

Fig 1 Linear IgA disease. Erythematous plaques with vesicopustules in the inguinal area.
(Courtesy of B Horvath, MD, PhD; Virginia Commonwealth University, Richmond.)

Fig 2 Linear IgA disease. Early lesion showing a subepidermal blister containing a few neutrophils, erythrocytes, and lymphocytes. There is loss of the dermal papillary connective tissue reminiscent of dermatitis herpetiformis.


Fig 3 Linear IgA disease. Neutrophil microabscesses indistinguishable from dermatitis herpetiformis are often present.

Fig 4 Linear IgA disease. This is a view of a very early lesion showing neutrophil tagging along the basement membrane region and fibrin deposition.

Fig 5 Linear IgA disease. The same specimen also showed multiple small subepidermal vesicles as shown in this field.

Fig 6 Linear IgA disease. IgA deposition along the dermal-epidermal junction on direct immunofluorescence.
Porphyria Cutanea Tarda

Definition

• Photosensitive subepidermal blistering disorder resulting from metabolic defect in the heme synthetic pathway as a result of mutation in the gene encoding for uroporphyrinogen decarboxylase; a more common predisposed, sporadic variant is also recognized

Clinical features

Epidemiology

• Autosomal dominant, but majority of cases are sporadic
• Usually presents in late childhood (familial form) to early adulthood (sporadic form)
• Rare cases associated with exposure to polyhalogenated aromatic hydrocarbons
• No clear gender predilection

Presentation

• Photosensitivity, with disease flares resulting from excessive exposure to sunlight, but also potential liver insults, such as alcohol, oral contraceptives, hepatitis C virus, HIV, hemochromatosis
• Tense vesicles and bullae photodistributed classically over dorsal hands, forearms
• Often see blister remnants, crusted erosions, dyspigmentation
• Associated scarring and milia formation characteristic
• Hypertrichosis on face, usually sideburn, malar areas
• Hair (scarring alopecia) and nails (photo-onycholysis) may be affected
• Drug-induced pseudoporphyria can create similar clinical picture, although lacking hypertrichosis
• Metabolic laboratory studies show elevated urinary porphyrins

Prognosis and treatment

• Chronic, waxing–waning course, punctuated by episodes of disease flares
• Risk for hepatocellular carcinoma (hepatitis C–related?)
• Skin fragility may impair daily function, work
• Sun protection essential to management
• Therapeutic phlebotomy common first-line therapy
• Hydroxycholoroquine or chloroquine helpful
• Chelation also may be effective

Pathology

Histology

• Paucicellular subepidermal blister with festooning of dermal papillae
• Thickened papillary vessels with hyalinization
• Dermal sclerosis marked in chronic lesions (sclerodermiform)

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