Eva Brehmer-Andersson Dermatopathology Eva Brehmer-Andersson Dermatopathology

With 138 Figures in 445 Separate Illustrations and 5 Tables

123 Eva Brehmer-Andersson Värtavägen 17 115 53 Stockholm Sweden

ISBN-10 3-540- 30245-X Springer-Verlag Berlin Heidelberg NewYork ISBN-13 978-3-540- 30245-2 Springer-Verlag Berlin Heidelberg NewYork

Library of Congress Control Number: 2006920598

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, speci.cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro.lms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law.

Springer is a part of Springer Science+Business Media springer.com © Springer-Verlag Berlin Heidelberg 2006 Printed in Germany

The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.

Product liability: the publishers cannot guarantee the accuracy of any information about dos- age and application contained in this book. In every individual case the user must check such information by consulting the relevant literature.

Editor: Gabriele Schröder, Heidelberg Desk Editor: Ellen Blasig, Heidelberg Production and Typesetting: LE-TEX Jelonek, Schmidt & Vöckler GbR, Leipzig Cover Design: Frido Steinen-Broo, EStudio Calamar, Spain

Printed on acid-free paper 24/3100/YL 5 4 3 2 1 0 Preface

The purpose of this book is to introduce future pathologists and dermatolo- gists to the exciting field of dermatopathology. During the past 40 years der- matopathology has become a big and important topic. There are today many excellent and comprehensive textbooks on the subject, but the overwhelming amount of material and increasing number of this kind of textbook make it difficult to start to discover new fields. I have chosen to focus on relevant pro- cesses in basic pathology and discuss how they work or are supposed to work in both common and unusual skin diseases, which I have been confronted with during a life-long practice in pathology and dermatopathology. I also focus on some controversial concepts prevailing and on the diversity in no- menclature. My expectation is to promote the understanding of pathogenesis in diseases of the skin and arouse an appetite for further and more compre- hensive studies, and hopefully even to inspire new fruitful investigations. In this respect, the book will even address those experienced in the specialty.

Eva Brehmer-Andersson March 2006 Acknowledgement

This book is based on experiences acquired at the Departments of Pathology of the University Hospitals in Lund and Umeå, and at the Karolinska Univer- sity Hospital and South Hospital in Stockholm, Sweden. In all these places I have had a close and inspiring collaboration with the respective Departments of Dermatology. I want to heartily thank all staff members who during the years, besides their own routine work, have willingly helped me with impor- tant things such as further sections and stainings, and searching for old slides, records and print-outs. I am deeply indebted to Sven Lindskog, Professor at the Department of Oral Histology, Karolinska Institute, Stockholm, for generously having put his photo laboratory at my disposal, and to Karl Gabor, colleague and photogra- pher, for valuable advice about adaptation of the photographic material. Contents

1 Requirements for a Good 4.1.4 Immune Response in Non-Lymphoid Diagnostic Result Tissues ...... 15 4.1.5 Cytokines and Cell Adhesion Molecules . . 15 1.1 Sampling Technique ...... 1 4.2 Innate Immunity ...... 16 1.2 The Consulting Form...... 1 4.2.1 The Complement System...... 17 1.3 Routine Processing ...... 2 4.2.1.1 The Classic Pathway ...... 17 1.4 Interpretation of Histopathologic Changes . 2 4.2.1.2 The Alternative Pathway ...... 17 4.3 Adverse Reactions of the Immune System . 17 4.3.1 Type I. Immediate Reactions ...... 17 2 The Dermal Blood Vasculature 4.3.2 Type II. Cytotoxic Antibody-Dependent Reactions...... 17 2.1 General Architecture of Blood Vessels . . . . 4 4.3.3 Type III. Reactions due to Circulating 2.1.1 Arteries...... 4 Immune Complex Activated by 2.1.2 Capillaries ...... 4 Complement...... 18 2.1.3 Veins ...... 4 4.3.4 Type IV. Cell-Mediated Hypersensitivity 2.1.4 The Endothelium ...... 5 Reactions...... 18 2.1.5 Arteriovenous Anastomoses ...... 5 4.4 The Skin Immune System ...... 18 2.2 The Microvasculature of the Skin ...... 5 4.4.1 Lymphocytes in Normal Skin ...... 18 References ...... 6 4.4.2 Langerhans Cells ...... 18 4.4.3 Keratinocytes ...... 19 4.5 The Immune Response and Skin Diseases . 19 3 The Dermal Lymphatic Vasculature References ...... 19

3.1 The Construction of Lymphatic Capillaries . 9 3.2 Lymphatic Capillaries in the Skin ...... 9 5 Cell and Vascular Response 3.3 Prelymphatics and Initial Lymphatics to Infection and Injury (Lymphatic Sinusoids, Blind Tubes) . . . . 10 References ...... 11 5.1 Inflammatory Cells ...... 21 5.1.1 Neutrophils ...... 21 5.1.2 Eosinophils ...... 21 4 The Immune Response 5.1.3 Lymphocytes ...... 21 5.1.4 Plasma Cells...... 22 4.1 Adaptive Immunity...... 12 5.1.5 Mast Cells ...... 22 4.1.1 B and T Cells ...... 12 5.1.6 Basophils...... 23 4.1.2 The Lymph Node ...... 13 5.1.7 Monocytes/Macrophages ...... 23 4.1.2.1 The Cortex—the Main Territory for B Cells 13 5.2 Acute Inflammation ...... 23 4.1.2.2 Paracortex or Deep Cortex—the Main 5.2.1 Active Phase...... 23 Territory for T Cells ...... 14 5.2.2 Healing Without Residue ...... 24 4.1.2.3 Medulla—the Area Between the Paracortex 5.2.3 Abscess Formation ...... 25 and the Hilus ...... 14 5.2.4 Healing with Fibrosis and Formation 25 4.1.3 The Recirculation of Lymphocytes . . . . . 14 5.2.4.1 Examples...... 25 X Contents

5.3 Chronic Inflammation ...... 26 7.4.3 Pathogenesis...... 43 5.3.1 Immune ...... 26 7.4.4 Examples...... 43 5.3.1.1 The Tuberculous ...... 27 7.4.5 Differential Diagnosis ...... 43 5.3.1.2 ...... 28 7.5 Category V: Lymphocytic/Monocytic Arterial 5.3.1.2.1 Example ...... 28 ...... 44 5.3.2 Foreign Body Granuloma ...... 28 7.5.1 Clinical Appearance ...... 44 5.3.3 Relevant Investigations...... 28 7.5.2 Histopathologic Appearance...... 44 5.4 Angiogenesis ...... 28 7.5.3 Examples...... 44 5.5 Cell Division...... 29 7.5.4 Comment ...... 49 References ...... 30 7.6 Category VI: Granulomatous Neutrophilic Arterial Vasculitis...... 49 7.6.1 Clinical Appearance ...... 49 6 Cell Death in the Living Body 7.6.2 Histopathologic Appearance...... 49 7.6.3 Examples...... 50 6.1 Accidental Cell Death ...... 31 7.6.4 Comment ...... 50 6.2 Apoptosis ...... 31 7.7 Category VII: Mixed Group ...... 50 6.2.1 Apoptosis in Embryonic Development . . . 32 7.7.1 Erythema Elevatum Diutinum ...... 51 6.2.2 Apoptosis in Postnatal Life...... 33 7.7.1.1 Clinical Appearance ...... 53 6.2.3 Relevant Investigations...... 33 7.7.1.2 Histopathologic Appearance...... 53 6.2.4 Apoptosis and the Skin...... 33 7.7.1.3 Example ...... 53 References ...... 34 7.7.1.4 Comment ...... 53 7.7.2 Granuloma Faciale ...... 55 7.7.2.1 Clinical Appearance ...... 55 7 Vasculitis 7.7.2.2 Histopathologic Appearance...... 55 7.7.2.3 Pathogenesis...... 55 7.1 Category I: Neutrophilic Venular Vasculitis 35 7.7.2.4 Example ...... 55 7.1.1 Clinical Appearance ...... 37 7.7.2.5 Comment ...... 55 7.1.2 Histopathologic Appearance...... 37 7.7.3 Angiolymphoid Hyperplasia with 7.1.3 Pathogenesis...... 37 Eosinophilia ...... 55 7.1.4 Examples...... 38 7.7.3.1 Example ...... 56 7.1.5 Variants of Leukocytoclastic Vasculitis . . . 38 7.7.3.2 Comment ...... 57 7.1.5.1 Henoch-Schönlein Purpura ...... 38 7.7.4 Bacillary Epithelioid Angiomatosis . . . . . 57 7.1.5.2 Infantile Acute Hemorrhagic Edema of the 7.7.4.1 Examples...... 59 Skin...... 39 7.7.5 Comment ...... 59 7.1.5.3 Urticarial Vasculitis...... 39 7.8 Nomenclature ...... 61 7.1.5.4 Recurrent Cutaneous Necrotizing 7.9 Conclusion...... 62 Eosinophilic Vasculitis ...... 40 References ...... 63 7.1.5.5 Pustular Vasculitis of the Hands...... 40 7.1.6 Differential Diagnosis ...... 40 7.2 Category II: Lymphocytic Venular 8 Skin Lesions due to Abnormalities Vasculitis...... 40 in Blood Components 7.2.1 Clinical Appearance ...... 40 7.2.2 Histopathologic Appearance...... 40 8.1 The Normal Coagulation/Fibrinolytic Balance 7.2.3 Pathogenesis...... 40 in the Coagulation System...... 65 7.2.4 Examples...... 40 8.2 Disseminated Intravascular Coagulation . . 65 7.2.5 Differential Diagnosis ...... 41 8.2.1 Example ...... 66 7.3 Category III: Granulomatous Venular 8.3 Thrombotic-Thrombocytopenic Purpura/ Vasculitis...... 41 Hemolytic-Uremic (TTP/HUS) Syndrome 66 7.3.1 Example ...... 42 8.3.1 Examples...... 66 7.4 Category IV: Neutrophilic Arterial 8.3.2 Comment ...... 67 Vasculitis...... 42 8.4 Hypercoagulability of Minor Severity . . . 68 7.4.1 Clinical Appearance ...... 43 8.4.1 Examples...... 68 7.4.2 Histopathologic Appearance...... 43 8.4.2 Comment ...... 70 XI

8.5 Skin Necrosis Induced by Treatment with 13.1.2 Histopathologic Appearance...... 88 Warfarin ...... 70 13.1.3 Relevant Investigations...... 90 8.6 Cryoglobulinemia...... 70 13.1.4 Examples...... 91 8.6.1 Example ...... 71 13.1.5 Comment ...... 92 8.7 Hereditary Hemoglobinopathies ...... 71 13.2 Malassezia furfur/Pityrosporum infections 93 8.7.1 Example ...... 72 13.2.1 Pityriasis (Tinea) Versicolor ...... 93 References ...... 74 13.2.1.1 Clinical appearance ...... 93 13.2.1.2 Histopathologic Appearance...... 93 13.2.2 Pityrosporum folliculitis ...... 93 9 Arteriosclerosis in the Skin 13.2.2.1 Clinical Appearance ...... 93 13.2.2.2 Histopathologic Appearance and 9.1 Arteriolosclerosis ...... 75 Pathogenesis...... 93 9.1.1 Hyaline Arteriolosclerosis ...... 75 13.2.3 Systemic Manifestation ...... 94 9.1.2 Hyperplastic Arteriolosclerosis ...... 75 13.3 Candidiasis ...... 95 9.2 Arteriosclerosis ...... 75 13.3.1 Clinical Appearance ...... 95 9.3 Examples...... 75 13.3.1.1 Skin Lesions ...... 95 9.4 Differential Diagnosis ...... 77 13.3.1.2 Oral Lesions ...... 95 13.3.1.3 Mucocutaneous Infection ...... 95 13.3.1.4 Chronic Mucocutaneous Candidiasis .... 95 10 Thromboangiitis Obliterans 13.3.1.5 Systemic Manifestation ...... 95 13.3.2 Histopathologic Appearance...... 95 10.1 Clinical Appearance ...... 78 13.3.3 Examples...... 97 10.2 Histopathologic Appearance...... 78 13.4 Aspergillosis ...... 97 10.3 Example ...... 78 13.4.1 Clinical Appearance ...... 97 References ...... 78 13.4.2 Histopathologic Appearance...... 97 13.4.3 Examples...... 97 References ...... 98 11 Angiotropic Lymphoma

11.1 Clinical and Histopathologic Appearances 80 14 Demodicidosis 11.2 Examples...... 80 11.3 Differential Diagnosis ...... 80 14.1 Characteristics of Demodex Mites . . . . 100 References ...... 82 14.2 Pathogenesis and Clinical Appearance . . 100 14.3 Example ...... 101 References ...... 101 12 Infections Caused by Common Pyogenic Bacteria 15 Infections Caused by 12.1 Streptococcal Infections ...... 83 Mycobacterium Tuberculosis, M. 12.2 Staphylococcal Infections ...... 83 Bovis, and Atypical Mycobacteria 12.2.1 Non-Bullous Impetigo ...... 83 12.2.2 Bullous Impetigo ...... 83 15.1 Mycobacterium Tuberculosis and M. Bovis 12.3 Anonymous Bacterial Infections ...... 83 Infections in the Skin...... 102 12.4 Examples...... 83 15.1.1 Primary Inoculation (Primary Complex, 12.4.1 Comment ...... 85 Tuberculous Chancre) ...... 102 12.5 Differential Diagnosis ...... 85 15.1.2 Tuberculosis Verrucosa Cutis ...... 102 Reference ...... 85 15.1.3 Lupus Vulgaris ...... 103 15.1.3.1 Clinical Appearance ...... 103 15.1.3.2 Histopathologic Appearance...... 103 13 Common Fungal Infections 15.1.3.3 Examples...... 103 15.1.4 Other Types of Skin Lesions due to Spreading 13.1 Dermatophytosis (Ringworm, Tinea).... 86 from Internal Organs...... 103 13.1.1 Clinical Appearance ...... 86 XII Contents

15.2 Infections in the Skin Caused by Atypical 17.3.1 Clinical Appearance ...... 119 Mycobacteria ...... 105 17.3.2 Histopathologic Appearance...... 119 15.2.1 Infection with M. Avium–Intracellulare 17.3.3 Example ...... 119 Complex ...... 105 17.4 Comment ...... 119 15.2.2 Infection with M. Malmoense ...... 105 References ...... 121 15.2.3 Infection with M. Marinum ...... 105 15.2.3.1 Clinical Appearance ...... 106 15.2.3.2 Histopathologic Appearance...... 106 18 Lyme Borreliosis 15.2.4 Infection with M. Fortuitum–Chelonae Complex ...... 106 18.1 Pathogenesis...... 122 15.2.5 Examples...... 106 18.2 Erythema Migrans ...... 122 15.3 Comment ...... 107 18.2.1 Clinical Appearance ...... 122 15.4 Differential Diagnosis ...... 108 18.2.3 Histopathologic Appearance...... 122 References ...... 108 18.2.3.1 Comment ...... 123 18.3 Borrelial Lymphocytoma...... 123 18.3.1 Clinical Appearance ...... 123 16 Leprosy 18.3.2 Histopathologic Appearance...... 123 18.3.3 Differential Diagnosis ...... 126 16.1 Pathogenesis...... 110 18.4 Acrodermatitis Chronica Atrophicans . . 126 16.2 Primary Neuritic Leprosy ...... 110 18.4.1 Clinical Appearance ...... 126 16.3 Cutaneous Leprosy ...... 110 18.4.2 Histopathologic Appearance...... 126 16.3.1 Indeterminate Leprosy ...... 110 18.4.2.1 Comment ...... 131 16.3.2 Tuberculoid Leprosy ...... 110 18.4.3 Differential Diagnosis ...... 131 16.3.3 Borderline Leprosy ...... 111 18.5 Methods to Prove the Presence of Spirochetes 16.3.4 Lepromatous Leprosy...... 111 in Borrelial Skin Lesions ...... 132 16.3.5 Example ...... 111 References ...... 132 16.3.5.1 Comment ...... 112 16.3.6 Reactions in Leprosy ...... 112 16.3.6.1 Type I...... 113 19 Leishmaniasis 16.3.6.2 Type II ( Leprosorum) ...... 113 19.1 Pathogenesis...... 134 16.3.7 The Paucibacillary and Multibacillary 19.2 Cutaneous Leishmaniasis ...... 134 Groups ...... 113 19.2.1 Clinical Appearance ...... 134 16.3.8 Classification According to Ridley . . . . 113 19.2.2 Histopathologic Appearance...... 134 16.3.9 Differential Diagnosis ...... 113 19.2.3 Example ...... 134 References ...... 113 19.2.3.1 Comment ...... 135 19.2.4 Differential Diagnosis ...... 135 References ...... 135 17 Syphilis

17.1 Primary Syphilis ...... 114 20 Herpes Simplex, Herpes 17.1.1 Clinical Appearance ...... 114 Zoster/Varicella, and 17.1.2 Histopathologic Appearance...... 114 Cytomegalovirus Infections 17.1.3 Examples...... 115 17.2 Secondary Syphilis ...... 115 20.1 Herpes Simplex and Herpes Zoster/Varicella 17.2.1 Clinical Appearance ...... 116 Virus Infections...... 136 17.2.1.1 Macular Syphilid ...... 116 20.1.1 Clinical Appearance and Pathogenesis . . 136 17.2.1.2 Papular Syphilid...... 116 20.1.2 Histopathologic Appearance...... 137 17.2.2 Histopathologic Appearance...... 116 20.1.3 Examples...... 138 17.2.3 Examples...... 116 20.1.4 Comment ...... 142 17.2.4 Differential Diagnosis ...... 119 20.1.5 Differential Diagnosis ...... 143 17.3 Late Benign Syphilis (Tertiary Syphilis) in the 20.1.5.1 Comment ...... 143 Skin...... 119 20.2 Cytomegalovirus Infection...... 143 XIII

20.2.1 Pathogenesis and Clinical Appearance . . 143 23.4.1 Comment ...... 167 20.2.2 Histopathologic Appearance...... 144 23.5 Differential Diagnosis ...... 169 20.2.3 Example ...... 144 References ...... 169 20.2.4 Differential Diagnosis ...... 146 References ...... 146 24 and Lichen Nitidus

21 Langerhans Cell Histiocytosis in 24.1 Lichen Planus ...... 170 Skin and Mucous Membranes 24.1.1 Clinical Appearance ...... 170 24.1.2 Histopathologic Appearance...... 170 21.1 Clinical Appearance ...... 147 24.1.3 Pathogenesis...... 173 21.2 Histopathologic Appearance...... 147 24.1.4 Differential Diagnosis ...... 173 21.3 Examples...... 149 24.2 Lichen Nitidus...... 174 21.4 Comment ...... 151 24.2.1 Clinical Appearance ...... 174 21.5 Pathogenesis...... 153 24.2.2 Histopathologic Appearance...... 174 21.6 Differential Diagnosis ...... 153 24.2.3 Pathogenesis...... 174 References ...... 153 24.2.4 Example ...... 174 References ...... 174

22 Dermatitis (Eczema) 25 Autoimmune Vesicular, Bullous, 22.1 Clinical Appearance ...... 155 and Pustular Dermatoses 22.1.1 Allergic Contact Dermatitis ...... 155 22.1.2 Irritant Contact Dermatitis ...... 155 25.1 The Pemphigus Group ...... 176 22.1.3 Atopic Dermatitis...... 155 25.1.1 Pemphigus Vulgaris ...... 177 22.1.4 Nummular Dermatitis ...... 156 25.1.1.1 Clinical Appearance ...... 177 22.1.5 Seborrheic Dermatitis ...... 156 25.1.1.2 Histopathologic Appearance...... 177 22.1.6 Stasis Dermatitis ...... 156 25.1.1.3 Pemphigus Vegetans of Neumann Type . 178 22.1.7 Allergic Contact Stomatitis ...... 156 25.1.1.4 Pemphigus Vegetans of Hallopeau Type . 178 22.2 Histopathologic Appearance...... 156 25.1.2 Pemphigus Foliaceus ...... 178 22.2.1 Acute Dermatitis ...... 156 25.1.2.1 Clinical Appearance ...... 178 22.2.2. Subacute Dermatitis ...... 158 25.1.2.2 Histopathologic Appearance...... 179 22.2.3 Chronic Dermatitis ...... 158 25.1.2.3 Pemphigus Erythematosus ...... 179 22.3 Examples...... 158 25.1.2.4 Pemphigus Herpetiformis ...... 179 22.4 Differential Diagnosis ...... 160 25.1.3 Pathogenesis...... 179 22.5 Erythroderma (Exfoliative Dermatitis) . . 160 25.1.4 Examples...... 181 22.5.1 Clinical Appearance ...... 160 25.1.5 Differential Diagnosis ...... 183 22.5.2 Histopathologic Appearance...... 160 25.1.5.1 Familial Benign Pemphigus (Haily-Haily 22.5.3 Example ...... 161 Disease) ...... 183 22.5.3.1 Comment ...... 162 25.1.5.2 Follicularis (Darier Disease) . . 185 References ...... 162 25.1.5.3 Transient Acantholytic Dermatosis (Grover Disease) ...... 185 25.1.5.4 Examples...... 187 23 25.2 Intraepidermal IgA Pustulosis (IgA Pemphigus) ...... 189 23.1 Clinical Appearance ...... 163 25.2.1 Clinical Appearance ...... 189 23.1.1 Psoriasis Vulgaris ...... 163 25.2.2 Histopathologic Appearance...... 190 23.1.2 Psoriasis Guttata ...... 163 25.2.3 Pathogenesis...... 190 23.1.3 Psoriasis Pustulosa ...... 163 25.2.4 Example ...... 190 23.1.4 Psoriatic Erythroderma ...... 163 25.2.5 Differential Diagnosis ...... 190 23.2 Histopathologic Appearance...... 163 25.2.6 Comment ...... 190 23.3 Pathogenesis...... 164 25.3 Paraneoplastic Pemphigus ...... 190 23.4 Examples...... 164 25.3.1 Clinical Appearance ...... 191 XIV Contents

25.3.2 Histopathologic Appearance...... 191 27.2 Necrolytic Migratory Erythema...... 210 25.3.3 Pathogenesis...... 191 27.2.1 Example ...... 212 25.3.4 Examples...... 192 27.3 Vesicular/Bullous Eruption in Systemic Lupus 25.3.5 Comment ...... 192 Erythematosus and Dermatomyositis . . 212 25.4 Autoimmune Subepidermal Vesicular and 27.3.1 Examples...... 212 Bullous Dermatoses...... 194 27.4 et Atrophicus ...... 212 25.4.1 Bullous Pemphigoid ...... 194 27.4.1 Example ...... 213 25.4.1.1 Clinical Appearance ...... 194 27.5 Bullous Pemphigoid ...... 213 25.4.1.2 Histopathologic Appearance...... 194 27.5.1 Example ...... 213 25.4.1.3 Pathogenesis...... 195 27.6 Comment ...... 213 25.4.1.4 Differential Diagnosis ...... 195 References ...... 213 25.4.2 Dermatitis Herpetiformis ...... 195 25.4.2.1 Clinical Appearance ...... 195 25.4.2.2 Histopathologic Appearance...... 195 28 Skin Lesions Due to Drugs 25.4.2.3 Pathogenesis...... 195 25.4.3 Linear IgA Dermatosis ...... 195 28.1 Acute Allergic Urticaria/Angioedema . . 215 25.4.4 Cicatricial Pemphigoid...... 197 28.1.1 Clinical Appearance ...... 215 25.4.5 Acquired Porphyria Cutanea Tarda (Sporadic 28.1.2 Histopathologic Appearance...... 215 or Type I) ...... 197 28.1.3 Pathogenesis...... 216 References ...... 197 28.1.4 Examples...... 216 28.2 Maculopapular Eruptions ...... 216 28.2.1 Clinical Appearance ...... 216 26 Recurrent Vesicular Eruptions 28.2.2 Histopathologic Appearance...... 217 28.2.3 Pathogenesis...... 217 26.1 Erythema Multiforme ...... 199 28.2.4 Differential Diagnosis ...... 217 26.1.1 Clinical Appearance ...... 199 28.3 Fixed Drug Eruptions ...... 217 26.1.2 Histopathologic Appearance...... 199 28.3.1 Clinical Appearance ...... 217 26.1.3 Pathogenesis...... 201 28.3.2 Histopathologic Appearance...... 217 26.1.4 Examples...... 201 28.3.3 Pathogenesis...... 217 26.1.5 Comment ...... 201 28.3.4 Examples...... 217 26.1.6 Differential Diagnosis ...... 202 28.4 Toxic Epidermal Necrolysis and Stevens- 26.2 ...... 202 Johnson Syndrome ...... 218 26.2.1 Clinical Appearance ...... 202 28.4.1 Clinical Appearance ...... 218 26.2.2 Histopathologic Appearance...... 202 28.4.2 Histopathologic Appearance...... 219 26.2.3 Pathogenesis...... 202 28.4.3 Pathogenesis...... 220 26.2.4 Example ...... 204 28.4.4 Examples...... 220 26.2.5 Differential Diagnosis ...... 204 28.4.4.1 Comment ...... 220 26.3 Pityriasis Lichenoides et Varioliformis 28.4.5 Differential Diagnosis ...... 221 Acuta...... 204 28.5 Acute Generalized Exanthematous 26.3.1 Clinical Appearance ...... 204 Pustulosis ...... 221 26.3.2 Histopathologic Appearance...... 205 28.5.1 Clinical Appearance ...... 222 26.3.3 Pathogenesis...... 205 28.5.2 Histopathologic Appearance...... 222 26.3.4 Examples...... 205 28.5.3 Pathogenesis...... 222 26.3.5 Comment ...... 207 28.5.4 Differential Diagnosis ...... 223 26.3.6 Differential Diagnosis ...... 208 28.6 Bullous Skin Lesions due to Photosensitivity References ...... 208 Reactions...... 223 28.6.1 Example ...... 223 28.6.2 Differential Diagnosis ...... 223 27 Profiles of the Epidermal/ 28.7 Interstitial Granulomatous Drug Reaction 224 Dermal Area in some Vesicular/ 28.7.1 Clinical Appearance ...... 224 Bullous Dermatoses 28.7.2 Histopathologic Appearance...... 224 28.7.3 Pathogenesis...... 224 27.1 Vesicular/Bullous Dermatitis (Eczema) . 210 28.7.4 Differential Diagnosis ...... 224 XV

28.8 Skin Lesions Provoked by Penicillamine . 224 29.3.3 Example ...... 234 28.8.1 Nonallergic Degenerative Lesions Induced by 29.4 Burns...... 234 Penicillamine ...... 224 29.4.1 Accidental and Self-Inflicted Burns .... 234 28.8.1.1 Clinical Appearance ...... 224 29.4.2 Late Therapeutic Radiation Dermatitis . . 235 28.8.1.2 Histopathologic Appearance...... 224 29.4.2.1 Clinical Appearance ...... 235 28.8.1.3 Example ...... 225 29.4.2.2 Histopathologic Appearance...... 235 28.8.1.4 Differential Diagnosis ...... 225 29.4.3 Phytophotodermatitis ...... 235 28.8.2 Allergic Skin Reactions Provoked by 29.4.4 Examples...... 236 Penicillamine ...... 225 29.5 Morsicatio Mucosae Oris ...... 238 28.9 Bullous Skin Lesions in Acute Drug 29.5.1 Clinical Appearance ...... 238 Intoxication and Coma...... 225 29.5.2 Histopathologic Appearance...... 238 28.9.1 Clinical Appearance ...... 225 29.5.3 Examples...... 238 28.9.2 Histopathologic Appearance...... 225 29.5.4 Comment ...... 238 28.9.3 Example ...... 225 29.5.5 Differential Diagnosis ...... 240 28.9.3.1 Comment ...... 228 29.6 Amalgam ...... 240 28.9.4 Pathogenesis...... 228 29.6.1 Clinical Appearance ...... 240 References ...... 229 29.6.2 Histopathologic Appearance...... 240 29.6.3 Example ...... 241 29.7 Chemical Burns in the Oral Mucosa . . . 241 29 Artifacts 29.7.1 Examples...... 243 References ...... 243 29.1 Friction Blisters and Scratch Marks.... 231 29.1.1 Clinical Appearance ...... 231 29.1.2 Histopathologic Appearance...... 231 30 Glossary 29.1.3 Pathogenesis...... 231 29.1.4 Examples...... 231 References ...... 250 29.2 Decubitus Ulcers ...... 234 29.3 Hematidrosis ...... 234 29.3.1 Clinical Appearance ...... 234 Subject Index ...... 251 29.3.2 Histopathologic Appearance...... 234 Abbreviations

ACA Acrodermatitis chronica atrophicans ICAM Intercellular adhesion molecule AGEP Acute generalized IFN Interferon exanthematous pustulosis IgA Immunoglobulin A AIDS Acquired immunodeficiency IgD Immunoglobulin D syndrome IgE Immunoglobulin E ALHE Angiolymphoid hyperplasia IgG Immunoglobulin G with eosinophilia IgM Immunoglobulin M B cells B lymphocytes IL Interleukin BEA Bacillary epithelioid angiomatosis kDa kiloDalton C Complement LCH Langerhans cell histiocytosis CAMs Cell adhesion molecules LFA Leukocyte function antigen c-ANCA Antineutrophilic LGC Langhans giant cell cytoplasmic antibodies LPS Lipopolysaccharide CD Common differentiation (antigen) MAC Macrophage activation antigen CD3 Molecular complex in T cells MBP Major basic protein CD4 Helper T cells MHC Major histocompatibility complex CD8 Suppressor T cells NK Natural killer (cells) CMV Cytomegalovirus PAS Periodic-acid-Schiff CSHRH Congenital self-healing PLC Pityriasis lichenoides chronica reticulohistiocytosis PLEVA Pityriasis lichenoides et DIC Disseminated intravascular varioliformis acuta coagulation PSR Polymerase chain reaction DNA Deoxyribonucleic acid RNA Ribonucleic acid EBV Epstein-Barr virus S-100 Protein expressed on ECP Eosinophilic cationic protein Langerhans cells EDN Eosinophilic derived neurotoxin SJ Stevens-Johnson (syndrome) EED Erythema elevatum diutinum SLE Systemic ELAM Endothelial leukocyte T cells T lymphocytes adhesion molecule TCR T-cell receptor region EM Erythema multiforme TEN Toxic epidermal necrolysis EORTC European Organization for Research TGF Transforming growth factor and Treatment of Cancer TNF Tumor necrosis factor ESR Erythrocyte sedimentation rate t-PA Tissue plasminogen activator FBGC Foreign body giant cell t-PAI Inhibitor of t-PA GM-CSF Granulocyte-macrophage TTP/HUS Thrombotic-thrombocytopenic colony-stimulating factor purpura /hemolytic- H&E Hematoxylin-eosin uremic syndrome HCMV Human cytomegalovirus VCAM Vascular cell adhesion molecule HIV Human immunodeficiency virus VEGF Vascular endothelial growth factor HL Hairy leukoplakia vG van Gieson HLA Human leukocyte antigen VLA Very late activation (integrins) HPV Human papilloma virus vWF von Willebrand factor HSV Herpes simplex virus VZV Varicella/herpes zoster virus XVIII

Magnification Magnification [= the objective × the factor of the microscope × a factor of the magnification device (depending on the distance used)] is mentioned in legends only when considered of special interest (i.e., to make it possible to compare the size of different vessels as in Figs. 2.3 and 9.2 and to give an idea of the size of microorganisms and other small particles as in Figs. 19.1 and 29.7. Indications of size and staining only at the end of the legends include all micrographs in the figure.