J. Ring, B. Przybilla, T. Ruzicka (Eds.) Handbook of Atopic Eczema Second Edition
J. Ring, B. Przybilla, T. Ruzicka (Eds.)
Handbook
of Atopic Eczema
Second Edition
With 187 Figures in 236 Parts and 113 Tables
Prof. Dr. Dr. Johannes Ring
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein Technische Universität München
Biedersteiner Straße 29, 80802 München, Germany
Prof. Dr. Bernhard Przybilla
Klinik und Poliklinik für Dermatologie und Allergologie Ludwig-Maximilians-Universität
Frauenlobstraße 9–11, 80337 München, Germany
Prof. Dr. Thomas Ruzicka
Klinik und Poliklinik für Dermatologie, Heinrich-Heine-Universität Moorenstraße 5, 40225 Düsseldorf, Germany
ISBN 3-540-23133-1 Springer-Verlag Berlin Heidelberg New York Library of Congress Control Number: 2005926887
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Preface
Atopic eczema is one of the most frequent inflammatory skin diseases and its preva- lence is rising. It presents major problems for patients and physicians as well as for researchers all over the world. Few diseases are discussed as heatedly. Atopic eczema seems to be in the midst of debates regarding scientific medicine versus complemen- tary medicine, and caught up in the “battle” among disciplines such as dermatology, pediatrics, and allergology. In spite of the great progress in experimental allergology and dermatology, where atopic eczema is a paradigm of scientific progress, there is still a wide gap between the theoretical knowledge and the practical everyday man- agement procedures in the physician’s office.
The burden of suffering is not confined to the individual affected with this excru- ciating pruritic skin disease; often whole families are disrupted and the complete environment of a patient is involved. The loss in quality of life, measured with stan- dard scales, is massive – as great as in people suffering from cancer!
At the World Dermatology Congress (Congressus Dermatologiae Mundi) in Mexico City in 1977 there was just one workshop dedicated to “atopic dermatitis”
which was attended by about 12 people; in the meantime, atopic eczema represents a focus of research and clinical work in many dermatology departments all over the world, and at our congresses numerous symposia and workshops are dedicated to the subject.
More than 15 years have passed since the first edition of this handbook. This is reflected in the total revision of almost all the chapters. New authors have been rec- ruited, and new topics have been included. However, the general format, namely the division into three major parts – clinical aspects, pathophysiology, and management – has been retained. Each part ends with a synopsis.
We, the editors, are proud to have attracted such a distinguished group of experts from all over the world; it can truly be stated that this “Handbook of Atopic Eczema”
covers the whole gamut of current knowledge in research and practice. At the end of each chapter the reader will find a comprehensive reference list.
We would like to thank Daniela Bolocan, Heike Föllmer, Brigitte Engelmann, and Christa Wandschneider for invaluable secretarial work, as well as Gabriele Schröder, Marion Philipp, Irmela Bohn and Ellen Blasig for assistance in the editorial process.
Finally, the intensive help of all the staff of the departments of dermatology and allergy at Munich TUM, Munich LMU and Düsseldorf is gratefully acknowledged.
Without the constant support of our co-workers, this work would never have been accomplished. Special thanks in this context go to PD Dr. Ulf Darsow (Munich TUM) and Dr. Carolyn Bauer (Munich LMU).
While this 2nd edition of our handbook developed, a new nomenclature for aller- gy and allergic diseases was suggested by a task force of the European Academy of Allergology and Clinical Immunology (EAACI) and later by the World Allergy Or- ganization (WAO) which particularily influenced the terms “atopic eczema” and
“atopic dermatitis”. Not all authors have adopted the new nomenclature. The terms
“atopic eczema” (AE) and “atopic dermatitis” (AD) are used interchangeably and still contain – if not precisely mentioned – also the “intrinsic”, “non IgE-associated”
forms of the disease.
Our primary motivation in producing this book was, and remains, the wish to improve the lives of the many patients suffering from eczema.
Munich and Düsseldorf, August 2005 Johannes Ring
Bernhard Przybilla Thomas Ruzicka VI Preface
Contents
I Clinical Aspects of Atopic Eczema 1 Atopy: Condition, Disease, or Syndrome?
J. Ring . . . 3
1.1 History . . . 3
1.2 Clinical Symptoms . . . 4
1.3 Etiopathophysiological Aspects . . . 5
1.4 Definition of Atopy . . . 7
1.5 Conclusion . . . 7
References . . . 7
2 The History of Atopic Eczema/Dermatitis A. Ta¨ıeb, D. Wallach, G. Tilles . . . 10
2.1 Introduction . . . 10
2.2 Precursors of Atopic Eczema . . . 10
2.3 Toward a Modern Definition . . . 14
2.4 Historical Landmarks in the Modern History of Atopic Eczema . . . 16
2.5 The History of Atopic Eczema Treatments . . . . 18
2.6 What History Tells Us Today . . . 18
References . . . 19
3 Epidemiology of Atopic Eczema T. Schäfer . . . 21
3.1 Definitions . . . 21
3.2 Diagnostic Criteria . . . 21
3.3 Assessment in Epidemiological Studies . . . 22
3.4 Measures of Frequency . . . 22
3.5 Trends and Frequency of Atopic Eczema. . . 23
3.6 Atopic Eczema in East and West Germany . . . . 23
3.7 Intrinsic and Extrinsic Atopic Eczema . . . 24
3.8 Risk Factors and Characteristics . . . 24
3.9 Prognostic Factors . . . 27
References . . . 27
4 The Burden of Atopic Eczema A.Y. Finlay . . . 31
4.1 Introduction . . . 31
4.2 Nature of the Burden . . . 31
4.3 Measurement of Burden . . . 32
4.4 Strategies for Improving Burden . . . 35
4.5 Declaration of Interest . . . 35
References . . . 35
5 Clinical Symptoms of Atopic Eczema M. Deleuran, A. Braae Olesen, K. Thestrup- Pedersen . . . 37
5.1 Introduction . . . 37
5.2 Evolution of Atopic Eczema . . . 38
5.3 Course of Atopic Eczema . . . 39
5.4 Some Typical Clinical Features . . . 40
5.5 Atopic Eczema in the Adult Patient . . . 42
5.6 The Prognosis of Atopic Eczema . . . 43
5.7 Atopic Eczema and Differential Diagnoses . . . 43
5.8 Conclusion . . . 43
References . . . 44
6 Atopic Eczema in Infants A. Ta¨ıeb, F. Boralevi . . . 45
6.1 Introduction . . . 45
6.2 Infantile Eczema: What It Is and What It Is Not . . . 45
6.3 Historical Background: Hall’s Thesis (1905) . . 46
6.4 Review of Current Diagnostic Criteria . . . 48
6.5 Time Course of Clinical Aspects in Infancy . . 49
6.6 Differential Diagnosis . . . 50
6.7 Complications . . . 53
6.8 Management . . . 54
6.9 Prognosis of Infantile Eczema . . . 59
6.10 Conclusions . . . 59
References . . . 59
7 Stigmata of the Atopic Constitution B. Przybilla, C. Bauer . . . 61
7.1 Features of Atopy . . . 61
7.2 Constitutional Stigmata of Atopy . . . 63
7.3 Constitutional Stigmata as Markers of Atopy 70 References . . . 72
8 Minimal Variants of Atopic Eczema
B. Wüthrich . . . 74
8.1 Localized Minimal Variants of Atopic Eczema . . . 74
8.2 Juvenile Plantar Dermatosis . . . 77
8.3 Juvenile Papular Dermatosis: The Papular Form of Atopic Eczema . . . 78
8.4 Patchy Pityriasiform Lichenoid Eczema: The Follicular Form of Atopic Eczema . . . 79
8.5 Comments . . . 81
References . . . 82
9 Diagnosis of Atopic Eczema S. Weidinger, J. Ring . . . 84
9.1 Introduction . . . 84
9.2 Morphology of Skin Lesions . . . 84
9.3 Morphological Variants . . . 86
9.4 Manifestations of Atopic Eczema at Special Body Areas . . . 88
9.5 Stigmata of Atopy . . . 89
9.6 Diagnostic Criteria for Atopic Eczema . . . 90
9.7 Differential Diagnosis of Atopic Eczema . . . 95
9.8 Allergy Diagnosis in Atopic Eczema . . . 96
References . . . 97
10 Differential Diagnosis of Atopic Eczema B. Wedi, A. Kapp . . . 100
10.1 Introduction . . . 100
10.2 Chronic Inflammatory Skin Diseases . . . 100
10.3 Infection and Infestation . . . 101
10.4 Immunologic Disorders . . . 101
10.5 Malignant Diseases . . . 102
10.6 Congenital Disorders . . . 102
10.7 Immunodeficiencies . . . 103
10.8 Metabolic Diseases . . . 104
10.9 Conclusion . . . 106
References . . . 107
11 Respiratory Symptoms in Atopic Eczema – Focus on Asthma and Early Treatment T. Haahtela . . . 108
11.1 Introduction . . . 108
11.2 Occurrence . . . 108
11.3 Risk Factors . . . 109
11.4 Early Treatment of Atopic Eczema or Rhinitis . . . 110
11.5 Early Treatment of Eosinophilic Inflammation and Asthma . . . 110
11.6 Improving Early Diagnosis . . . 112
11.7 Present and Future . . . 112
References . . . 113
12 Complications and Diseases Associated with Atopic Eczema D. Vieluf, J. Rieker, T. Ruzicka . . . 115
12.1 Introduction . . . 115
12.2 Infections in Atopic Eczema: General Remarks . . . 115
12.3 Bacterial Infections . . . 115
12.4 Mycotic Infections . . . 115
12.5 Viral Infections . . . 117
12.6 Parasitic Disorders . . . 123
12.7 Exfoliative Erythroderma . . . 124
12.8 Associated Ocular Diseases . . . 124
12.9 Associated Gastrointestinal Disorders . . . . 126
12.10 Cystic Fibrosis . . . 127
12.11 Steroid-Responsive Nephrotic Syndrome . . 128
12.12 Metabolic Disorders . . . 128
12.13 Cutaneous Lymphomas . . . 129
12.14 Anhidrotic Congenital Ectodermal Dysplasia . . . 129
12.15 Growth Impairment . . . 129
12.16 Sleep Disturbances . . . 130
12.17 Psoriasis . . . 130
12.18 Photosensitivity . . . 130
12.19 Drug Sensitivity . . . 130
12.20 Insect Venom Allergy . . . 131
12.21 Congenital Perceptive Hearing Loss . . . 131
12.22 Vitiligo . . . 131
12.23 Hair Anomalies . . . 131
12.24 Netherton’s Syndrome . . . 132
12.25 Down’s Syndrome . . . 132
12.26 Sudden Infant Death Syndrome . . . 132
12.27 Dubowitz Syndrome . . . 132
12.28 Eczematous Skin Lesions in X-Linked Immunodeficiency with Hyperimmuno- globulinemia M Syndrome . . . 132
12.29 Cutaneous Amyloidosis . . . 133
12.30 Gynecological Diseases . . . 133
12.31 Neurological Disorders . . . 133
12.32 Autoimmune Disorders . . . 133
12.33 Hypoproteinemia . . . 134
12.34 Pityriasis Rosea . . . 134
12.35 Palmar-Plantar Keratoderma of Unna- Thost . . . 134
12.36 Multiple Dermatofibrosarcomata . . . 134
References . . . 134 VIII Contents
13 Diseases Rarely Associated with Atopic Eczema
A. Braae Olesen . . . 144
13.1 Atopic Eczema and Insulin-Dependent Diabetes Mellitus . . . 144
13.2 Atopic Eczema and Psoriasis . . . 145
13.3 Atopic Eczema and Rheumatoid Arthritis . . 146
13.4 Atopic Eczema and Melanocytic Nevi . . . 147
13.5 Concluding Remarks . . . 147
References . . . 148
14 Natural History of Atopic Eczema B. Wüthrich . . . 150
14.1 Studies on the Long-Term Prognosis of Atopic Eczema After Childhood . . . 150
14.2 Studies Reporting Data on the Long-Term Prognosis of Atopic Eczema Based on Community Samples . . . 150
14.3 The Atopic March: Atopic Eczema and the Development of Asthma and Hay Fever . . . . 151
14.4 The Atopic March: Early Sensitization to Foods and Aeroallergens Is the Main Risk Factor for the Development of Asthma . . . 153
14.5 Children with the Non-IgE-Associated Variety of Atopic Eczema (Intrinsic Atopic Eczema) Rarely Get Asthma . . . 154
14.6 Conclusions . . . 155
References . . . 155
15 Dry Skin N. Y. Schürer . . . 157
15.1 The Stratum Corneum . . . 157
15.2 Pathophysiology of Dry Skin . . . 159
15.3 Conclusion . . . 163
References . . . 163
16 Occupational Aspects of Atopic Eczema with Emphasis on Atopic Hand Eczema T.L. Diepgen . . . 166
16.1 Introduction . . . 166
16.2 Clinical Aspects of Atopic Hand Eczema . . . . 166
16.3 Atopic Skin Diathesis and Hand Eczema . . . . 168
16.4 The Triangle of Atopic Eczema, Hand Eczema, and Occupational Skin Disease . . . . 168
16.5 Sick Leave and Changing Occupations Due to Atopic Eczema . . . 170
16.6 Atopic Eczema as an Effect Modifier or Risk Factor for Hand Eczema . . . 171
16.7 Attributable Risk for Occupational Skin Diseases . . . 172
16.8 On the Quantification of Risk . . . 173
16.9 Occupational Guidelines for Individuals with Atopic Eczema . . . 175
16.10 Key Points . . . 175
References . . . 176
17 Allergic Contact Dermatitis and Atopic Eczema A. Schnuch, W. Uter, K. Reich . . . 178
17.1 Clinical Findings . . . 178
17.2 Preimmunologic Mechanisms in Allergic Contact Dermatitis . . . 181
17.3 Atopic Eczema and Impairment of the Epidermal Skin Barrier . . . 183
17.4 Immunologic Mechanisms in Allergic Contact Dermatitis . . . 184
17.5 The Immunopathogenesis of Atopic Eczema – Possible Interference with Allergic Contact Dermatitis . . . 188
17.6 Conclusion . . . 191
References . . . 194
18 Immunodeficiency Syndromes and Atopic Eczema M. Laimer, H. Hintner, P. Fritsch . . . 202
18.1 Primary and Secondary Immune Deficiencies . . . 202
18.2 The Immune Defect in Atopic Eczema . . . . 203
18.3 Eczema in Primary Immunodeficiency Disorders . . . 204
18.4 Primary Immunodeficiency Disorders Frequently Associated with Atopic Eczema 204 18.5 Primary Immunodeficiency Disorders Occasionally or Possibly Associated with Atopic Eczema . . . 207
18.6 Is Atopic Eczema a Feature of Acquired Immunodeficiency Disorders? . . . 210
18.7 Comments and Conclusions . . . 210
References . . . 211
19 Atopic Diseases in Families M. Uehara . . . 213
19.1 Introduction . . . 213
19.2 Family History of Atopic Diseases . . . 213
19.3 Subtypes of Atopic Dermatitis . . . 214
19.4 Personal History of Atopic Respiratory Diseases . . . 214
19.5 Descendant Family History of Atopic Eczema 215 19.6 Paternal and Maternal Effect . . . 215
References . . . 216 Contents IX
20 Histopathologic and Ultrastructural Aspects of Atopic Eczema
M. Fartasch . . . 218
20.1 Eczematous Skin in Atopic Eczema . . . 218
20.2 Noneczematous Skin in Atopics . . . 219
References . . . 220
21 Pathophysiology and Clinical Manifestation of Itch in Atopic Eczema U. Darsow, E. Ripphoff, J. Ring . . . 222
21.1 Introduction . . . 222
21.2 Pathophysiology . . . 222
21.3 Problems of Measuring Clinical Itch with Visual Analog Scales . . . 223
21.4 The Eppendorf Itch Questionnaire . . . 224
21.5 Therapy for Itch . . . 225
References . . . 227
22 Clinical Basics of Atopic Eczema: Synopsis B. Przybilla, J. Ring, T. Ruzicka . . . 228
22.1 Epidemiology . . . 228
22.2 Clinical Presentation . . . 228
22.3 Histopathology . . . 229
22.4 Diagnosis . . . 229
22.5 Complications . . . 230
22.6 Associated Diseases . . . 230
22.7 Psychosomatic Aspects . . . 231
22.8 Natural History . . . 231
II Pathophysiology of Atopic Eczema 23 Clinical Genetics of Atopic Eczema F. Schultz Larsen . . . 235
23.1 Introduction . . . 235
23.2 Methods for Mapping Complex Diseases . . . 235
23.3 Atopic Eczema/Dermatitis Syndrome . . . 235
23.4 Linkage Studies . . . 236
23.5 Statistics of Linkage Analysis . . . 237
23.6 Candidate Gene . . . 237
23.7 Genome Screens in Atopic Eczema . . . 238
23.8 Candidate Genes in Atopic Eczema . . . 238
23.9 Other Chromosomes . . . 240
23.10 Maternal Effect and Genomic Imprinting . . 241
23.11 Conclusions . . . 241
References . . . 241
24 The Molecular Genetics of Atopy W. Cookson . . . 244
24.1 Introduction . . . 244
24.2 Candidate Genes . . . 244
24.3 Genome Screens . . . 245
24.4 Single Gene Disorders . . . 248
24.5 Maternal Effects . . . 249
24.6 Conclusions . . . 249
References . . . 250
25 Genetics of Atopic Eczema Young-Ae Lee, C. Söderhäll, U. Wahn . . . 255
25.1 Genetic Epidemiology . . . 255
25.2 Approaches to the Genetic Analysis of Atopic Eczema . . . 256
25.3 Conclusion . . . 262
References . . . 263
26 Mechanisms of IgE-Regulation M. Worm, T. Jakob . . . 265
26.1 Introduction . . . 265
26.2 Mechanisms of Allergic Sensitization: Allergen Uptake, Processing, and Presentation . . . 265
26.3 Activation, Migration, and Maturation of Antigen-Presenting Cells . . . 266
26.4 T Cell Activation and Polarization of the T Cell Response . . . 267
26.5 Origin and Maturation of B Cells . . . 269
26.6 Immunoglobulins . . . 270
26.7 Isotype Switching . . . 270
26.8 Additional Factors of IgE Regulation . . . 271
26.9 Therapeutic Implications . . . 272
References . . . 273
27 Dendritic Cells in Atopic Eczema T. Kopp, G. Stingl . . . 275
27.1 Introduction . . . 275
27.2 Antigen-Presenting Cell Subpopulations in Atopic Eczema Skin . . . 275
27.3 Types of Antigen-Presenting Cells in Peripheral Blood . . . 278
27.4 IgE-Facilitated Amplification of the Immune Response . . . 279
27.5 Role of Dendritic Cells in Initiating, Maintaining, and/or Silencing the Allergic Tissue Inflammation . . . 281
27.6 Effects of Topical Calcineurin Inhibitors . . . . 282
References . . . 282
28 Inflammatory Dendritic Epidermal Cells A. Wollenberg . . . 288
28.1 Langerhans Cells . . . 288
28.2 Inflammatory Dendritic Epidermal Cells . . . 288
28.3 Delineation of Inflammatory Dendritic Epidermal Cells from Langerhans Cells . . . . 289
X Contents
28.4 Ontogenesis of Inflammatory Dendritic
Epidermal Cells . . . 290
28.5 Inflammatory Dendritic Epidermal Cells Are Present in Early Atopic Eczema Lesions . . . 290
28.6 Inflammatory Dendritic Epidermal Cells Are Present in Extrinsic and Intrinsic Atopic Eczema . . . 290
28.7 IgE-Receptor Expression of Inflammatory Dendritic Epidermal Cells . . . 290
28.8 In Situ Expression of Costimulatory Molecules on Inflammatory Dendritic Epidermal Cells . . . 291
28.9 Pinocytosis and Receptor-Mediated Endocytosis of Epidermal Dendritic Cells 291 28.10 Diagnostic Epidermal Dendritic Cell Phenotyping . . . 292
28.11 Epidermal Dendritic Cells in Skin Lesions Under Topical Therapy . . . 292
28.12 Outlook . . . 293
References . . . 293
29 Extrinsic and Intrinsic Atopic Eczema N. Novak, T. Bieber . . . 296
29.1 Introduction . . . 296
29.2 Allergic Atopic Eczema . . . 296
29.3 Skin . . . 297
29.4 The Role of Aeroallergens and Food Allergens and the Atopy Patch Test . . . 299
29.5 The Role of Microbial Infections . . . 300
29.6 Blood . . . 300
29.7 Conclusion . . . 301
References . . . 301
30 Mast Cells in the Skin M.K. Church . . . 303
30.1 Mast Cell Activation . . . 304
30.2 Mast Cell Mediators . . . 305
30.3 Conclusions . . . 308
References . . . 309
31 The Role of Eosinophils in Atopic Eczema D. Simon . . . 313
31.1 Evidence for Eosinophil Involvement in Atopic Eczema . . . 313
31.2 Mechanisms Causing Eosinophilia . . . 315
31.3 Activation of and Immunoregulation by Eosinophils . . . 317
31.4 Eosinophils as a Therapeutic Target . . . 318
References . . . 319
32 Role of T Cells in Atopic Eczema M. Akdis, J. Verhagen, K. Blaser, C.A. Akdis 323 32.1 Skin-Selective Homing of T Cells . . . 323
32.2 Mechanisms of Cutaneous Lymphocyte- Associated Antigen Expression on Human T Cells . . . 324
32.3 T Cell Chemotaxis in Atopic Eczema . . . 325
32.4 Role of IL-5 and IL-13 in Atopic Eczema . . . . 326
32.5 Role of Apoptosis in Allergic Inflammation 326 32.6 Conclusion . . . 329
References . . . 329
33 Keratinocytes in Atopic Eczema G. Girolomoni, F. Mascia, C. Dattilo, A. Giannetti, S. Pastore . . . 332
33.1 Introduction . . . 332
33.2 Keratinocytes Actively Participate in the Initiation and Amplification of Skin Inflammatory Responses . . . 332
33.3 The Role of Keratinocytes in the Recruit- ment of Inflammatory Cells in Atopic Eczema . . . 333
33.4 Keratinocytes from Atopic Eczema Patients Produce Increased Amounts of GM-CSF and Other Proinflammatory Cytokines . . . 335
33.5 Dysregulated Activation of AP-1 Trans- cription Factors May Be Implicated in the Enhanced Expression of Inflammatory Genes by Atopic Eczema Keratinocytes . . . 335
33.6 Concluding Remarks . . . 336
References . . . 336
34 Inflammatory Mediators and Chemokines in Atopic Eczema B. Homey, T. Ruzicka . . . 340
34.1 The Chemokine Superfamily . . . 340
34.2 Chemokine Receptors and TH1 and TH2 Cells 342 34.3 Memory T Cell Recruitment to the Skin . . . . 342
34.4 Dendritic Cell Trafficking . . . 344
34.5 Eosinophil Recruitment . . . 345
34.6 Conclusion and Perspective . . . 346
References . . . 346
35 Cytokines in Atopic Dermatitis (Eczema) H. Mizutani . . . 350
35.1 Introduction . . . 350
35.2 Genetic Background and Cytokines . . . 350
35.3 Th1 and Th2 Cytokines . . . 350
35.4 Infiltrating Cells and Keratinocytes . . . 351 Contents XI
35.5 Chronic Lesion and Fibrosis . . . 352
35.6 Acquired Type Atopic Eczema/Innate Type Atopic Eczema and IL-18 . . . 352
35.7 Effects of Skin Lesions on Systemic Immunity . . . 353
35.8 Intrinsic and Extrinsic Atopic Eczema. . . 353
35.9 Conclusion . . . 354
References . . . 354
36 Neuropeptides and Atopic Eczema F. Fantini, C. Pincelli . . . 357
36.1 Neuropeptides and the Skin . . . 357
36.2 Role of Neuropeptides in Atopic Eczema . . . . 358
36.3 Neurotrophins and Atopic Eczema . . . 359
References . . . 360
37 Epidermal Lipids in Atopic Eczema E. Proksch, R. Fölster-Holst, J.-M. Jensen . . . 362
37.1 Introduction . . . 362
37.2 Physiological Role of Lipids in the Epidermis . . . 362
37.3 Abnormalities of Epidermal Lipids in Atopic Eczema . . . 363
37.4 Impaired Ceramide Content and Metabolism in Atopic Eczema . . . 363
37.5 Ceramides Bound to Cornified Envelope Proteins in Atopic Eczema . . . 366
37.6 Roles for Fatty Acids in Atopic Eczema . . . 366
37.7 Disturbed Epidermal Barrier Function and Enhanced Skin Allergen Penetration in Atopic Eczema . . . 368
37.8 Lipids in the Treatment of Atopic Eczema . . 368
References . . . 369
38 The Phenomenon of Irritable Skin in Atopic Eczema J. Huss-Marp, B. Eberlein-König, J. Ring . . . . 373
38.1 Introduction . . . 373
38.2 Definition of Irritable Skin . . . 373
38.3 Quantification of Irritable Skin . . . 373
38.4 Definition of Irritable Skin in Atopic Eczema . . . 374
38.5 Clinical Evidence of Irritable Skin in Atopic Eczema . . . 376
38.6 Experimental Evidence of Irritable Skin in Atopic Eczema . . . 376
38.7 Pathophysiology of Irritable Skin in Atopic Eczema . . . 377
38.8 Conclusion . . . 378
References . . . 378
39 Environmental Pollution and Atopic Eczema B. Eberlein-König, J. Huss-Marp, H. Behrendt, J. Ring . . . 381
39.1 Introduction . . . 381
39.2 Formaldehyde . . . 381
39.3 Conclusion . . . 387
References . . . 388
40 The Role of Inhalant Allergens in Atopic Dermatitis E.A. Erwin, J.A. Woodfolk, T.A.E. Platts-Mills 390 40.1 Introduction . . . 390
40.2 Parallels to Allergic Disease . . . 391
40.3 Atopy Patch Tests . . . 391
40.4 Immunology . . . 392
40.5 Avoidance . . . 394
40.6 The Relevance of Other Allergens . . . 395
40.7 Conclusion . . . 396
References . . . 396
41 Role of Food Allergy in Atopic Eczema T. Werfel, K. Breuer . . . 399
41.1 Introduction . . . 399
41.2 Prevalence of Food Allergy in Atopic Eczema 399 41.3 Late Eczematous Reactions to Foods in Atopic Eczema . . . 400
41.4 Rate of Late Reactions to Challenges with Foods . . . 400
41.5 Predictive Values of Diagnostic Tools . . . 401
41.6 Allergen-Specific T Cell Responses in Atopic Eczema . . . 402
41.7 Pollen-Associated Food Allergy in Atopic Eczema . . . 402
References . . . 403
42 Staphylococcus Aureus and Atopic Eczema M. Mempel . . . 406
42.1 Skin Colonization . . . 406
42.2 Mechanisms of Adherence . . . 406
42.3 Virulence Factors . . . 407
42.4 Concluding Remarks . . . 408
References . . . 408
43 Animal Models of Atopic Eczema A. Tanaka, H. Matsuda . . . 410
43.1 Introduction . . . 410
43.2 Spontaneous Animal Models for Atopic Eczema . . . 410
43.3 Inducible Animal Models of Atopic Eczema 415 43.4 Gene-operated Animal Models for Atopic Eczema . . . 415 XII Contents
43.5 Final Remarks . . . 415
References . . . 416
44 Autoantibodies in Atopic Eczema N. Mothes, I. Mittermann, K. Aichberger, P. Valent, R. Valenta . . . 417
44.1 Introduction . . . 417
44.2 Similarities and Cross-Reactivities Between Environmental Allergens and Human Proteins: The Concept of IgE Autoimmunity is Reborn . . . 418
44.3 The Discovery that the Occurrence of IgE Autoantibodies Is Frequently Associated with Atopic Eczema . . . 419
44.4 Identification of IgE-Reactive Autoantigens by Molecular Cloning . . . 420
44.5 How Intracellular Antigens Can Contribute to the Pathogenesis of Atopic Eczema . . . 421
44.6 IgE Autoreactivity as a Possible Marker for Chronic Inflammation and Tissue Damage in Atopic Eczema . . . 421
44.7 IgG Autoantibodies in Atopic Eczema Patients . . . 421
44.8 Pathomechanisms of IgE Autoreactivity . . . 422
References . . . 422
45 Pathophysiology of Atopic Eczema: Synopsis J. Ring, T. Ruzicka, B. Przybilla . . . 426
45.1 Introduction . . . 426
45.2 Genetic Predisposition . . . 426
45.3 Disturbed Skin Barrier Function (“Dry Skin”) . . . 427
45.4 Itch as a Major Symptom of Eczema . . . 427
45.5 Psychosomatic Interaction and Autonomic Nervous System Dysregulation . . . 427
45.6 Role of Allergy in Atopic Eczema . . . 428
45.7 Role of IgE-Mediated Sensitization . . . 428
45.8 Role of Microbial Colonization and Infection . . . 428
45.9 Role of Contact Allergy . . . 429
45.10 Role of Irritants and Pollutants . . . 429
45.11 Conclusion . . . 429
III Management of Patients with Atopy Eczema 46 Primary Prevention of Atopy U. Wahn, R. Nickel, S. Illi, S. Lau, C. Grüber, E. Hamelmann . . . 433
46.1 Introduction and Definition . . . 433
46.2 The Natural History of Atopic Manifestations . . . 433
46.3 Hereditary Factors . . . 434
46.4 Nongenetic Factors . . . 435
46.5 The Domestic Environment . . . 435
46.6 Possible Consequences for Prevention . . . 436
46.7 Primary Prevention . . . 437
46.8 Secondary Prevention . . . 438
46.9 Perspectives and Challenges . . . 438
References . . . 438
47 Role of Allergy Testing in Atopic Eczema U. Darsow, J. Ring . . . 441
47.1 Introduction . . . 441
47.2 Food Allergy in Atopic Eczema . . . 441
47.3 Practical Approach to the Patient with Suspected Food Allergy and AE . . . 442
47.4 Aeroallergens and Atopic Eczema . . . 443
47.5 Atopy Patch Test with Aeroallergens . . . 444
47.6 Outlook . . . 446
References . . . 447
48 Probiotics in Atopic Eczema C. Schnopp . . . 449
48.1 The Hygiene Hypothesis . . . 449
48.2 Primary Prevention Strategies in Atopic Eczema . . . 449
48.3 Probiotics for Primary Prevention in High-Risk Families . . . 450
48.4 Suggested Mechanisms . . . 452
48.5 Remaining Questions . . . 453
48.6 Conclusion . . . 453
References . . . 454
49 Measuring Disturbed Barrier Function in Atopic Eczema S. Seidenari, F. Giusti . . . 456
49.1 Transepidermal Water Loss (TEWL) . . . 456
49.2 Skin Hydration and TEWL . . . 457
49.3 Skin Lipids and TEWL . . . 458
49.4 Reactivity to Irritants . . . 458
49.5 Barrier Function in Atopic Patients Without Dermatitis . . . 459
49.6 TEWL and Topical Agents for Atopic Eczema . . . 459
References . . . 460
50 Basic Topical Therapy with Emollients in Atopic Eczema W. Gehring . . . 463
50.1 Introduction . . . 463 Contents XIII
50.2 Amphiphilic Systems . . . 464
50.3 Hydrophilic Systems . . . 465
50.4 Desired Vehicle Effects: Hydration of the Stratum Corneum and Induction of a Diffusion Barrier Against Hydrophilic Irritants . . . 466
50.5 Modulation of Vehicle Effects by Glycerol or Urea . . . 466
50.6 Vehicle Influence upon Biologic Effect of Topically Applied Drugs . . . 466
References . . . 467
51 Syndets in the Treatment of Atopic Eczema O. Braun-Falco, H.C. Korting . . . 468
51.1 Cleansing of Eczematous Skin – The Scope of the Problem . . . 468
51.2 The Development of Synthetic Detergents – A Real Option . . . 469
51.3 Desirable and Undesirable Effects of Syndets on Human Skin – the Role of pH . . . 471
51.4 Syndets and Eczematous Skin – Clinical Assessment . . . 474
References . . . 474
52 Topical Treatment with Glucocorticoids M. Kerscher, S. Williams, P. Lehmann . . . 477
52.1 Introduction . . . 477
52.2 Mechanism of Action . . . 478
52.3 Corticosteroid Classification . . . 480
52.4 Local and Systemic Unwanted Effects of Topical Glucocorticoids . . . 482
52.5 Influence of the Vehicle on the Effect of Topical Corticosteroid Preparations . . . 484
52.6 Additional Active Ingredients in Topical Corticosteroid Preparations . . . 485
52.7 Acceptance of the Use of Topical Corticosteroids . . . 486
52.8 Principles of Topical Treatment with Corticosteroids in Atopic Eczema . . . 487
52.9 Topical Corticosteroids Versus Topical Inhibitors of Calcineurin . . . 488
References . . . 489
53 Antimicrobial Therapy in Atopic Eczema A. Gauger, J. Ring . . . 492
53.1 Antiseptic Therapy . . . 492
53.2 Antibiotic Therapy . . . 493
53.3 Nonantibiotic Therapy . . . 495
53.4 Antimycotic Therapy . . . 496
53.5 Antiviral Therapy . . . 497
53.6 Future Perspectives . . . 498
53.7 Conclusion . . . 499
References . . . 499
54 Antihistamines in Atopic Eczema T. Zuberbier . . . 503
54.1 Introduction . . . 503
54.2 First Generation Antihistamines . . . 503
54.3 Second-Generation Antihistamines . . . 504
54.4 Clinical Studies . . . 504
References . . . 505
55 Climatotherapy in Atopic Eczema E. Vocks . . . 507
55.1 Influence of Climate on Atopic Eczema . . . 507
55.2 History of Climatotherapy . . . 508
55.3 Climate and Weather, Climate Adaptation . . 511
55.4 Human Biometeorological Research . . . 512
55.5 Basic Principles of Climatotherapy . . . 513
55.6 Climatotherapy in Atopic Eczema . . . 513
55.7 Application of Climatotherapy . . . 516
55.8 Therapy Results . . . 517
55.9 Conclusion . . . 520
References . . . 520
56 Skin Care in Atopic Eczema M. Kerscher, S. Williams . . . 524
56.1 Introduction . . . 524
56.2 General Recommendations . . . 525
56.3 Cleansing Sebostatic Skin in Atopic Eczema 526 56.4 Rehydrating Sebostatic Skin in Atopic Eczema 528 56.5 Decorative Cosmetic . . . 531
References . . . 531
57 Dietary Management of Atopic Eczema C. Kugler . . . 534
57.1 Definitions . . . 534
57.2 Prevalence of Adverse Reaction to Food in Atopic Eczema . . . 534
57.3 Diagnosis . . . 534
57.4 Diagnostic Types of Diet . . . 535
57.5 Nutritional Recommendations When There Is a Food Allergy . . . 537
57.6 Prognosis for Food Allergies . . . 537
References . . . 538
58 Phototherapy for Atopic Eczema J. Krutmann, A. Morita . . . 539
58.1 Introduction . . . 539
58.2 UVA1 Phototherapy for Acute, Severe Atopic Eczema . . . 539 XIV Contents
58.3 Phototherapy of Chronic, Moderate Atopic
Eczema . . . 540
58.4 Phototherapy of Atopic Hand and Foot Eczema . . . 541
58.5 Mechanism of Action . . . 541
58.6 Concluding Remarks . . . 541
References . . . 542
59 Atopic Eczema – Psychosomatic and Psychobiological Aspects U. Gieler . . . 544
59.1 Introduction and Historical Aspects . . . 544
59.2 Quality of Life in Atopic Eczema . . . 544
59.3 Psychological Aspects – Comorbidity with Atopic Eczema . . . 545
59.4 Stress and Atopic Eczema . . . 546
59.5 Psychoimmunology . . . 546
59.6 Coping and Compliance in Atopic Eczema . . . 548
59.7 Psychodynamic Aspects in Atopic Eczema . . . 548
59.8 Family Aspects . . . 549
59.9 Patient Management Programs . . . 549
59.10 Measures to Influence the Itch- Scratch Cycle . . . 550
59.11 Measures to Reduce Negative Effects on Social Relationships by Atopic Eczema Prevention Programs . . . 551
59.12 Status of the Empirical Research Concern- ing Atopic Eczema Prevention Programs . . 551
59.13 The Psychological Training Program in Atopic Eczema Prevention . . . 553
References . . . 553
60 Phosphodiesterase4 Inhibitors for Atopic Eczema L.F. Santamaria-Babi . . . 557
60.1 General Anti-inflammatory Effects of PDE 4 Inhibitors . . . 558
60.2 PDE 4 Inhibitors in Skin Inflammation . . . 558
60.3 Possible Effects of PDE 4 Inhibitors in Different Phases of Atopic Eczema . . . 559
60.4 Conclusion . . . 561
References . . . 561
61 Music Therapy in Atopic Eczema D. Münch . . . 565
61.1 When Is It Reasonable to Use Music Therapy? . . . 565
61.2 Forms of Music Therapy . . . 566
61.3 Skin and Psyche . . . 567
61.4 Use of Musical Components in Music Therapy . . . 568
61.5 Effect of Music on Humans: Conclusion . . . 568
61.6 Conclusion . . . 568
References . . . 569
62 Topical Immunomodulators in the Treatment of Atopic Eczema S. Reitamo, A. Remitz . . . 570
62.1 Introduction . . . 570
62.2 Activation of Inflammatory Cells in Atopic Eczema . . . 570
62.3 The Mode of Action of Topical Immunomodulatory Agents . . . 570
62.4 Staphylococcal Colonization Contributes to Severity of Atopic Eczema . . . 571
62.5 Treatment with Topical Immunomodulators Does Not Suppress Connective Tissue . . . . 571
62.6 Efficacy of Topical Immunomodulators Used as Monotherapy in Atopic Eczema . . . 571
62.7 Efficacy of Topical Immunomodulators Used Together with Topical Corticosteroids 572 62.8 Comparison of Tacrolimus Ointment and Pimecrolimus Cream . . . 572
62.9 Safety . . . 573
62.10 Adverse Events Are Related to Disease Severity . . . 573
62.11 Does Topical Immunomodulation Increase the Risk of Skin Cancer? . . . 573
62.12 Practical Use of Topical Immuno- modulators . . . 574
62.13 Conclusions . . . 574
References . . . 574
63 Eczema School: Practical Approaches in an Efficient Module of Tertiary Prevention Programs M. Premerlani, Y. Ludewig, C. Schnopp, J. Ring . . . 576
63.1 Introduction . . . 576
63.2 Eczema School at the Wolfgang Children’s Hospital in Davos, Switzerland . . . 577
63.3 Pedagogic Background of Eczema Schooling . . . 578
63.4 Introduction to Eczema School Sessions . . 578
63.5 Pedagogic Modules for the Main Part . . . 578
63.6 Pedagogic Methods for the Conclusion . . . . 579
63.7 Pedagogic Tools to Increase Self-Esteem and Self-Respect . . . 579
Contents XV
63.8 Organization of Eczema School . . . 579
63.9 Conclusion . . . 580
References . . . 580
64 Unconventional Treatments in Atopic Eczema T. Schäfer . . . 582
64.1 Definition . . . 582
64.2 Usage in the General Population . . . 582
64.3 Usage of Complementary Alternative Medicine for Atopic Eczema . . . 583
64.4 Utilization of Complementary Alternative Medicine by Dermatologists . . . 584
64.5 Specific Complementary Alternative Medicine Modalities . . . 585
64.6 Phytotherapy . . . 586
64.7 Chinese Herbal Medicine . . . 586
64.8 Acupuncture . . . 586
64.9 Autologous Blood Therapy . . . 587
64.10 Bioresonance . . . 587
64.11 Homoeopathy . . . 587
64.12 Massage Therapy and Aroma Therapy . . . . 587
64.13 Salt Baths . . . 588
64.14 Vitamins and Minerals . . . 588
64.15 Harmful Effects . . . 589
References . . . 589
65 Alternative Medicine for Atopic Eczema: A Comment R. Happle . . . 592
65.1 Romanticism . . . 592
65.2 Traditional Chinese Medicine Causing Complete Renal Failure . . . 592
65.3 Acupuncture . . . 593
65.4 Homeopathy . . . 593
65.5 Alternative Medicine Will Always Exist . . . 594
References . . . 594
66 Therapy of Atopic Eczema: Synopsis T. Ruzicka, S. Artik, J. Ring, B. Przybilla . . . 596
66.1 Introduction . . . 596
66.2 Skin Care . . . 597
66.3 Glucocorticoids . . . 598
66.4 Antihistamines . . . 598
66.5 Anti-infectious Treatment . . . 599
66.6 Ultraviolet Treatment . . . 599
66.7 Diet . . . 600
66.8 Environmental Control and Prevention . . . 601
66.9 Psychotherapeutic Approaches . . . 602
66.10 Immunomodulators and Immuno- suppressive Drugs . . . 602
66.11 Unconventional Therapy Options . . . 603
66.12 Summary and Outlook . . . 603
Subject Index . . . 605 XVI Contents
List of Contributors
Dr. Karl Aichberger
Division of Immunopathology, Department of Patho- physiology, Vienna General Hospital, AKH, Medical School, University of Vienna, Währinger Gürtel 18 – 20, 1090 Vienna, Austria
Prof. Dr. Cezmi A. Akdis
Swiss Institute of Allergy and Asthma Research (SIAF), Obere Straße 22, 7270 Davos, Switzerland Prof. Dr. Mübeccel Akdis
Swiss Institute of Allergy and Asthma Research (SIAF), Obere Str. 22, 7270 Davos, Switzerland Dr. Susanne Artik
Klinik und Poliklinik für Dermatologie, Heinrich-Heine-Universität, Moorenstr. 5, 40225 Düsseldorf, Germany
Dr. Carolyn Bauer
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Frauenlobstr. 9 – 11, 80337 München, Germany Prof. Dr. Heidrun Behrendt
ZAUM-Zentrum Allergie und Umwelt,
Division Environmental Dermatology and Allergology, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Prof. Dr. Thomas Bieber
Klinik und Poliklinik für Dermatologie,
Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany
Prof. Dr. Kurt Blaser
Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, 7270 Davos, Switzerland
Dr. Franck Boralevi
Pediatric Dermatology Unit and Department of Dermatology, Centre Hospitalier Universitaire of Bordeaux, France
Dr. Anne Braae Olesen
Department of Dermatology, Aarhus University Hospital, 8000 Aarhus C, Denmark
Prof. Dr. Dr. h.c. mult. Otto Braun-Falco
Dermatologische Klinik und Poliklinik, Ludwig- Maximilians-Universität, Frauenlobstr. 9 – 11, 80337 München, Germany
Dr. Kristine Breuer
Klinik und Poliklinik für Dermatologie und Venerologie, Medizinische Hochschule Hannover, Ricklinger Str. 5, 30449 Hannover, Germany Prof. Martin K. Church, PhD
Southampton General Hospital,
Dermatopharmacology, Level South Block, Southampton, SO16 6YD, UK
Prof. William Cookson
University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK PD Dr. Ulf Darsow
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Dr. Cristina Dattilo
Istituto Dermopatico dell’Immacolata, IRCCS, Via dei Monti di Creta 104, 00167, Rome, Italy
Dr. Mette Deleuran
Department of Dermatology, Aarhus University Hospital, 8000 Aarhus C, Denmark
Prof. Dr. Thomas L. Diepgen
Universitätsklinikum Heidelberg, Abt. Klinische Sozialmedizin, Thibautstr. 3, 69115 Heidelberg, Germany
PD Dr. Bernadette Eberlein-König
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Elizabeth A. Erwin
Division of Allergy and Immunology, University of Virginia, P.O. Box 801355, Charlottesville, VA 22908 – 1355, USA
Dr. Fabrizio Fantini
Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Prof. Dr. Manig´e Fartasch
Universitätsklinikum Erlangen, Hautklinik, Hartmannstr. 14, 91052 Erlangen, Germany Prof. Andrew Y. Finlay
Department of Dermatology, University of Wales, College of Medicine, Heath Park, Cardiff CF14 4XN, UK
PD Dr. Regina Fölster-Holst
Universitäts-Hautklinik Kiel, Schittenhelmstr. 7, 24105 Kiel, Germany
Prof. Dr. Peter Fritsch
Universitätsklinik für Dermatologie und Venerologie, Anichstr. 35, 6020 Innsbruck, Austria
Dr. Anke Gauger
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Prof. Dr. Wolfgang Gehring
Städtisches Klinikum Karlsruhe, Hautklinik, Karlsruhe, Germany
Prof. Dr. Alberto Giannetti
Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy
Prof. Dr. Uwe Gieler
Medizinisches Zentrum für Psychosomatische Medizin, Klinik für Psychosomatik und Psychotherapie, Universitätsklinikum Gießen, Ludwigstr. 76, 35392 Gießen, Germany Prof. Dr. Giampiero Girolomoni
Istituto Dermopatico dell’Immacolata, IRCCS, Via dei Monti di Creta 104, 00167, Rome, Italy
Dr. Francesca Giusti
Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Dr. Christoph Grüber
Department of Paediatric Pneumology and Immunology, Charit´e, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany Prof. Dr. Tari Haahtela
Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, P.O. Box 160, 00029, HUS, Finland
PD Dr. Eckhard Hamelmann
Department of Paediatric Pneumology and Immunology, Charit´e, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany Prof. Dr. Rudolf Happle
Klinik für Dermatologie und Allergologie, Klinikum der Philipps-Universität, Deutschhausstr. 9,
35033 Marburg, Germany Prof. Dr. H. Hintner
St.-Johanns-Spital, Landesklinik für Dermatologie, Müllner Hauptstr. 48, 5020 Salzburg, Austria Prof. Dr. Bernhard Homey
Universitätsklinikum Düsseldorf, Heinrich-Heine- Universität, Moorenstr. 5, 40225 Düsseldorf, Germany Dr. Johannes Huss-Marp
ZAUM-Zentrum Allergie und Umwelt,
Division Environmental Dermatology and Allergology, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Dr. Sabine Illi
Department of Paediatric Pneumology and Immunology, Charit´e, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany XVIII List of Contributors
PD Dr. Thilo Jakob
Division of Environmental Dermatology and Allergy, GSF National Research Center for Environment and Health & ZAUM Center for Allergy and Environment at the Department of Dermatology and Allergy Biederstein, Technical University Munich, Biedersteiner Str. 29, 80802 Munich, Germany Dr. Jens-Michael Jensen
Universitäts-Klinikum Schleswig-Holstein, Campus Kiel, Klinik für Dermatologie, Venerologie und Allergologie, Universitäts-Hautklinik,
Schittenhelmstr. 7, 24105 Kiel, Germany Prof. Dr. Alexander Kapp
Klinik und Poliklinik für Dermatologie und Venerologie, Medizinische Hochschule Hannover, Ricklinger Str. 5, 30449 Hannover, Germany Prof Dr. Martina Kerscher
Universität Hamburg, Fachbereich Chemie, von Melle Park 8, 20146 Hamburg, Germany
Dr. Tamara Kopp
Universitätsklinik für Dermatologie,
Immundermatologie und infektiöse Hauterkrankungen, Währinger Gürtel 18 – 20, 1090 Wien, Austria
Prof. Dr. Hans C. Korting
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Frauenlobstr. 9 – 11, 80337 München, Germany Prof. Dr. Jean Krutmann
Institut für Umweltmedizinische Forschung Heinrich-Heine-Universität Düsseldorf gGmbH, Auf ’m Hennekamp 50, 40225 Düsseldorf, Germany Claudia Kugler
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Dr. Michael Laimer
St.-Johanns-Spital, Landesklinik für Dermatologie, Müllner Hauptstr. 48, 5020 Salzburg, Austria PD Dr. Susanne Lau
Department of Paediatric Pneumology and Immunology, Charit´e, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Prof. Dr. Young-Ae Lee
Pediatric Pneumology and Immunology, Charit´e, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
Prof. Dr. Percy Lehmann
Klinik für Dermatologie, Allergologie und Umweltmedizin, Arrenberger Str. 20, 42117 Wuppertal, Germany
Dr. Yvette Ludewig
Hochgebirgsklinik, Davos-Wolfgang, Switzerland Dr. Francesca Mascia
Istituto Dermopatico dell’Immacolata, IRCCS, Via dei Monti di Creta 104, 00167, Rome, Italy
Prof. Hiroshi Matsuda
Laboratory of Clinical Immunology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology,
3 – 5-8 Saiwai-cho, Fuchu, Tokyo 183 – 8509, Japan PD Dr. Martin Mempel
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany
Dr. Irene Mittermann
Division of Hematology and Hemostaseology, Dept. of Internal Medicine I, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18 – 20, Vienna, Austria
Prof. Dr. Hitoshi Mizutani
Department of Dermatology, Mie University, Faculty of Medicine, 2 – 174 Edobashi, Tsu, Mie 514 – 8507, Japan
Dr. Akimichi Morita
Department of Environmental and Gerontological Dermatology, Nagoya City University, Nagoya City, Japan
Dr. Nadine Mothes
Division of Immunopathology, Department of Pathophysiology, Vienna General Hospital, AKH, Medical School, University of Vienna, Währinger Gürtel 18 – 20, 1090 Vienna, Austria
Daniela Münch
Promenade 113, 7270 Davos Platz, Switzerland
List of Contributors XIX
Dr. R. Nickel
Department of Paediatric Pneumology and Immunology, Charit´e, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany PD Dr. Natalija Novak
Klinik und Poliklinik für Dermatologie,
Universitätskliniken Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany
Dr. Saveria Pastore
Istituto Dermopatico dell’Immacolata, IRCCS, Via dei Monti di Creta 104, 00167, Rome, Italy Prof. Carlo Pincelli
Institute of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Prof. Dr. Thomas A.E. Platts-Mills
UVA Asthma & Allergic Diseases Center, P.O. Box 801355, Charlottesville, VA 22908, USA
Martina Premerlani
Allergieklinik, Zentrum für Kinder und Jugendliche, Hochgebirgsklinik, Davos-Wolfgang, Switzerland Prof. Dr. Ehrhardt Proksch
Department of Dermatology, University of Kiel, Schittenhelmstr. 7, 24105 Kiel, Germany Prof. Dr. Bernhard Przybilla
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität, Frauenlobstr. 9 – 11, 80337 München, Germany Prof. Dr. Kristian Reich
Abt. Dermatologie und Venerologie, Bereich Humanmedizin, Universität Göttingen, von-Siebold-Str. 3, 37075 Göttingen, Germany Prof. Dr. Sakari Reitamo
Department of Dermatology, Hospital for Skin and Allergic Diseases, University of Helsinki, Meilahdenti 2, 00250 Helsinki, Finland
Dr. Anita Remitz
Department of Dermatology, Hospital for Skin and Allergic Diseases, University of Helsinki, Meilahdenti 2, 00250 Helsinki, Finland
Juliane Rieker
Hohensteiner Institut, Schloss Hohenstein, 74357 Bönnigheim, Germany
Prof. Dr. Dr. Johannes Ring
Klinik und Poliklinik für Dermatologie und Allergo- logie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany Dr. Esther Ripphoff
Klinik und Poliklinik für Dermatologie und Allergo- logie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany Prof. Dr. Thomas Ruzicka
Klinik und Poliklinik für Dermatologie, Heinrich-Heine-Universität, Moorenstrasse 5, 40225 Düsseldorf, Germany
Dr. Luis F. Santamaria-Babi
Almirall Prodesfarma, Research Center, Cardener, 68 – 74, 08024 Barcelona, Spain
Prof. Dr. Torsten Schäfer
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Institut für Sozialmedizin, Beckergrube 43 – 47, 23552 Lübeck, Germany Dr. Christina Schnopp
Klinik und Poliklinik für Dermatologie und Allergo- logie am Biederstein, Technische Universität München, Biedersteiner Str. 29, 80802 München, Germany Prof. Dr. Axel Schnuch
IVDK-Zentrale, Universitäts-Hautklinik, von-Siebold-Str. 3, 37075 Göttingen, Germany Prof. Dr. Nanna Y. Schürer
University of Osnabrück, Department of Dermatology, Human Sciences, Sedanstr. 115, 49090 Osnabrück, Germany
Dr. Finn Schultz Larsen
Dermatology Clinic, Dronningensgade 72, 7000 Fredericia, Denmark
Prof. Dr. Stefania Seidenari
Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy Dr. Dagmar Simon
Inselspital Bern, Dermatologische Klinik, Freiburgstr. 4, 3010 Bern, Switzerland Dr. Cilla Söderhäll
Pediatric Pneumology and Immunology, Charit´e, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
XX List of Contributors
