Springer handbook of atopic eczema 2nd ed

J. Ring, B. Przybilla, T. Ruzicka (Eds.)
Second Edition

Handbook of Atopic Eczema


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

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Preface

Atopic eczema is one of the most frequent inflammatory skin diseases and its prevalence 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 complementary 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 management procedures in the physician’s office.
The burden of suffering is not confined to the individual affected with this excruciating 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 standard 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 recruited, 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).

VI

Preface

While this 2nd edition of our handbook developed, a new nomenclature for allergy 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 Organization (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


Contents

I

Clinical Aspects of Atopic Eczema

1

Atopy: Condition, Disease, or Syndrome?

J. Ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.1 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.2 Clinical Symptoms . . . . . . . . . . . . . . . . . . . . . . . .
1.3 Etiopathophysiological Aspects . . . . . . . . . . . . .
1.4 Definition of Atopy . . . . . . . . . . . . . . . . . . . . . . .
1.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3
3
4
5
7
7
7

2

The History of Atopic Eczema/Dermatitis
A. Ta¨ıeb, D. Wallach, G. Tilles . . . . . . . . . . . . . .
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2 Precursors of Atopic Eczema . . . . . . . . . . . . . . .
2.3 Toward a Modern Definition . . . . . . . . . . . . . . .
2.4 Historical Landmarks in the Modern History
of Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . . .
2.5 The History of Atopic Eczema Treatments . . . .
2.6 What History Tells Us Today . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10

10
10
14
16
18
18
19

3

Epidemiology of Atopic Eczema
T. Schäfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1 Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2 Diagnostic Criteria . . . . . . . . . . . . . . . . . . . . . . .
3.3 Assessment in Epidemiological Studies . . . . . .
3.4 Measures of Frequency . . . . . . . . . . . . . . . . . . . .
3.5 Trends and Frequency of Atopic Eczema. . . . . .
3.6 Atopic Eczema in East and West Germany . . . .
3.7 Intrinsic and Extrinsic Atopic Eczema . . . . . . .
3.8 Risk Factors and Characteristics . . . . . . . . . . . .
3.9 Prognostic Factors . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

21
21
21
22
22
23
23

24
24
27
27

4

The Burden of Atopic Eczema
A.Y. Finlay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2 Nature of the Burden . . . . . . . . . . . . . . . . . . . . . .
4.3 Measurement of Burden . . . . . . . . . . . . . . . . . . .

31
31
31
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. ThestrupPedersen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2 Evolution of Atopic Eczema . . . . . . . . . . . . . . .
5.3 Course of Atopic Eczema . . . . . . . . . . . . . . . . . .
5.4 Some Typical Clinical Features . . . . . . . . . . . . .
5.5 Atopic Eczema in the Adult Patient . . . . . . . . .

5.6 The Prognosis of Atopic Eczema . . . . . . . . . . .
5.7 Atopic Eczema and Differential Diagnoses . . .
5.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

37
37
38
39
40
42
43
43
43
44

6

Atopic Eczema in Infants
A. Ta¨ıeb, F. Boralevi . . . . . . . . . . . . . . . . . . . . . .
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.2 Infantile Eczema: What It Is and What
It Is Not . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3 Historical Background: Hall’s Thesis (1905) . .
6.4 Review of Current Diagnostic Criteria . . . . . .
6.5 Time Course of Clinical Aspects in Infancy . .
6.6 Differential Diagnosis . . . . . . . . . . . . . . . . . . . .
6.7 Complications . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.8 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.9 Prognosis of Infantile Eczema . . . . . . . . . . . . .

6.10 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

45
45
45
46
48
49
50
53
54
59
59
59

7

Stigmata of the Atopic Constitution
B. Przybilla, C. Bauer . . . . . . . . . . . . . . . . . . . . .
7.1 Features of Atopy . . . . . . . . . . . . . . . . . . . . . . . .
7.2 Constitutional Stigmata of Atopy . . . . . . . . . . .
7.3 Constitutional Stigmata as Markers of Atopy
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

61
61
63
70
72

VIII

Contents

8

Minimal Variants of Atopic Eczema
B. Wüthrich . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1 Localized Minimal Variants of Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.2 Juvenile Plantar Dermatosis . . . . . . . . . . . . . . .
8.3 Juvenile Papular Dermatosis: The Papular
Form of Atopic Eczema . . . . . . . . . . . . . . . . . . .
8.4 Patchy Pityriasiform Lichenoid Eczema:
The Follicular Form of Atopic Eczema . . . . . .
8.5 Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

74
74
77
78
79
81
82

9

Diagnosis of Atopic Eczema
S. Weidinger, J. Ring . . . . . . . . . . . . . . . . . . . . . .
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.2 Morphology of Skin Lesions . . . . . . . . . . . . . . .
9.3 Morphological Variants . . . . . . . . . . . . . . . . . . .
9.4 Manifestations of Atopic Eczema at Special
Body Areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.5 Stigmata of Atopy . . . . . . . . . . . . . . . . . . . . . . . .
9.6 Diagnostic Criteria for Atopic Eczema . . . . . .
9.7 Differential Diagnosis of Atopic Eczema . . . . .
9.8 Allergy Diagnosis in Atopic Eczema . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

84
84
84
86
88
89
90
95
96
97

10

Differential Diagnosis of Atopic Eczema
B. Wedi, A. Kapp . . . . . . . . . . . . . . . . . . . . . . . .
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
10.2 Chronic Inflammatory Skin Diseases . . . . . .

10.3 Infection and Infestation . . . . . . . . . . . . . . . . .
10.4 Immunologic Disorders . . . . . . . . . . . . . . . . .
10.5 Malignant Diseases . . . . . . . . . . . . . . . . . . . . .
10.6 Congenital Disorders . . . . . . . . . . . . . . . . . . . .
10.7 Immunodeficiencies . . . . . . . . . . . . . . . . . . . .
10.8 Metabolic Diseases . . . . . . . . . . . . . . . . . . . . . .
10.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11
11.1
11.2
11.3
11.4
11.5
11.6

Respiratory Symptoms in Atopic Eczema –
Focus on Asthma and Early Treatment
T. Haahtela . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Early Treatment of Atopic Eczema or
Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Early Treatment of Eosinophilic
Inflammation and Asthma . . . . . . . . . . . . . . . .
Improving Early Diagnosis . . . . . . . . . . . . . . .

100
100

100
101
101
102
102
103
104
106
107

108
108
108
109
110
110
112

11.7 Present and Future . . . . . . . . . . . . . . . . . . . . . . 112
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
12

Complications and Diseases Associated
with Atopic Eczema
D. Vieluf, J. Rieker, T. Ruzicka . . . . . . . . . . .
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
12.2 Infections in Atopic Eczema:
General Remarks . . . . . . . . . . . . . . . . . . . . . .
12.3 Bacterial Infections . . . . . . . . . . . . . . . . . . . .
12.4 Mycotic Infections . . . . . . . . . . . . . . . . . . . . .

12.5 Viral Infections . . . . . . . . . . . . . . . . . . . . . . .
12.6 Parasitic Disorders . . . . . . . . . . . . . . . . . . . .
12.7 Exfoliative Erythroderma . . . . . . . . . . . . . . .
12.8 Associated Ocular Diseases . . . . . . . . . . . . .
12.9 Associated Gastrointestinal Disorders . . . .
12.10 Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . .
12.11 Steroid-Responsive Nephrotic Syndrome . .
12.12 Metabolic Disorders . . . . . . . . . . . . . . . . . . .
12.13 Cutaneous Lymphomas . . . . . . . . . . . . . . . . .
12.14 Anhidrotic Congenital Ectodermal
Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12.15 Growth Impairment . . . . . . . . . . . . . . . . . . .
12.16 Sleep Disturbances . . . . . . . . . . . . . . . . . . . .
12.17 Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12.18 Photosensitivity . . . . . . . . . . . . . . . . . . . . . . .
12.19 Drug Sensitivity . . . . . . . . . . . . . . . . . . . . . . .
12.20 Insect Venom Allergy . . . . . . . . . . . . . . . . . .
12.21 Congenital Perceptive Hearing Loss . . . . . .
12.22 Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12.23 Hair Anomalies . . . . . . . . . . . . . . . . . . . . . . .
12.24 Netherton’s Syndrome . . . . . . . . . . . . . . . . . .
12.25 Down’s Syndrome . . . . . . . . . . . . . . . . . . . . .
12.26 Sudden Infant Death Syndrome . . . . . . . . . .
12.27 Dubowitz Syndrome . . . . . . . . . . . . . . . . . . .
12.28 Eczematous Skin Lesions in X-Linked
Immunodeficiency with Hyperimmunoglobulinemia M Syndrome . . . . . . . . . . . . . .
12.29 Cutaneous Amyloidosis . . . . . . . . . . . . . . . .
12.30 Gynecological Diseases . . . . . . . . . . . . . . . . .
12.31 Neurological Disorders . . . . . . . . . . . . . . . . .
12.32 Autoimmune Disorders . . . . . . . . . . . . . . . . .

12.33 Hypoproteinemia . . . . . . . . . . . . . . . . . . . . . .
12.34 Pityriasis Rosea . . . . . . . . . . . . . . . . . . . . . . .
12.35 Palmar-Plantar Keratoderma of UnnaThost . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12.36 Multiple Dermatofibrosarcomata . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

115
115
115
115
115
117
123
124
124
126
127
128
128
129
129
129
130
130
130
130
131
131
131
131

132
132
132
132

132
133
133
133
133
134
134
134
134
134


Contents

13

Diseases Rarely Associated with Atopic
Eczema
A. Braae Olesen . . . . . . . . . . . . . . . . . . . . . . . .
13.1 Atopic Eczema and Insulin-Dependent
Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . .
13.2 Atopic Eczema and Psoriasis . . . . . . . . . . . . .
13.3 Atopic Eczema and Rheumatoid Arthritis . .
13.4 Atopic Eczema and Melanocytic Nevi . . . . . .
13.5 Concluding Remarks . . . . . . . . . . . . . . . . . . . .

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

144
144
145
146
147
147
148

14

Natural History of Atopic Eczema
B. Wüthrich . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14.1 Studies on the Long-Term Prognosis of
Atopic Eczema After Childhood . . . . . . . . . . .
14.2 Studies Reporting Data on the Long-Term
Prognosis of Atopic Eczema Based on
Community Samples . . . . . . . . . . . . . . . . . . . .
14.3 The Atopic March: Atopic Eczema and the
Development of Asthma and Hay Fever . . . .
14.4 The Atopic March: Early Sensitization to
Foods and Aeroallergens Is the Main Risk
Factor for the Development of Asthma . . . . .
14.5 Children with the Non-IgE-Associated
Variety of Atopic Eczema (Intrinsic Atopic
Eczema) Rarely Get Asthma . . . . . . . . . . . . . .
14.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

150
150

150
151

153

154
155
155

15

Dry Skin
N. Y. Schürer . . . . . . . . . . . . . . . . . . . . . . . . . . .
15.1 The Stratum Corneum . . . . . . . . . . . . . . . . . . .
15.2 Pathophysiology of Dry Skin . . . . . . . . . . . . .
15.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16
16.1
16.2
16.3
16.4
16.5
16.6
16.7

Occupational Aspects of Atopic Eczema

with Emphasis on Atopic Hand Eczema
T.L. Diepgen . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical Aspects of Atopic Hand Eczema . . . .
Atopic Skin Diathesis and Hand Eczema . . . .
The Triangle of Atopic Eczema, Hand
Eczema, and Occupational Skin Disease . . . .
Sick Leave and Changing Occupations Due
to Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . .
Atopic Eczema as an Effect Modifier or
Risk Factor for Hand Eczema . . . . . . . . . . . . .
Attributable Risk for Occupational Skin
Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

157
157
159
163
163

166
166
166
168
168
170
171
172

16.8 On the Quantification of Risk . . . . . . . . . . .

16.9 Occupational Guidelines for Individuals
with Atopic Eczema . . . . . . . . . . . . . . . . . . . .
16.10 Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

173
175
175
176

17

Allergic Contact Dermatitis and Atopic
Eczema
A. Schnuch, W. Uter, K. Reich . . . . . . . . . . .
17.1 Clinical Findings . . . . . . . . . . . . . . . . . . . . . .
17.2 Preimmunologic Mechanisms in Allergic
Contact Dermatitis . . . . . . . . . . . . . . . . . . . .
17.3 Atopic Eczema and Impairment of the
Epidermal Skin Barrier . . . . . . . . . . . . . . . . .
17.4 Immunologic Mechanisms in Allergic
Contact Dermatitis . . . . . . . . . . . . . . . . . . . .
17.5 The Immunopathogenesis of Atopic
Eczema – Possible Interference with
Allergic Contact Dermatitis . . . . . . . . . . . . .
17.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

178
178

181
183
184

188
191
194

18

Immunodeficiency Syndromes and Atopic
Eczema
M. Laimer, H. Hintner, P. Fritsch . . . . . . . . .
18.1 Primary and Secondary Immune
Deficiencies . . . . . . . . . . . . . . . . . . . . . . . . . .
18.2 The Immune Defect in Atopic Eczema . . . .
18.3 Eczema in Primary Immunodeficiency
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18.4 Primary Immunodeficiency Disorders
Frequently Associated with Atopic Eczema
18.5 Primary Immunodeficiency Disorders
Occasionally or Possibly Associated with
Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . .
18.6 Is Atopic Eczema a Feature of Acquired
Immunodeficiency Disorders? . . . . . . . . . . .
18.7 Comments and Conclusions . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

202
202

203
204
204

207
210
210
211

19

Atopic Diseases in Families
M. Uehara . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
19.2 Family History of Atopic Diseases . . . . . . . .
19.3 Subtypes of Atopic Dermatitis . . . . . . . . . . .
19.4 Personal History of Atopic Respiratory
Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19.5 Descendant Family History of Atopic Eczema
19.6 Paternal and Maternal Effect . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

213
213
213
214
214
215
215
216

IX


X

Contents

20

Histopathologic and Ultrastructural
Aspects of Atopic Eczema
M. Fartasch . . . . . . . . . . . . . . . . . . . . . . . . . . .
20.1 Eczematous Skin in Atopic Eczema . . . . . . .
20.2 Noneczematous Skin in Atopics . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

218
218
219
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
22.1
22.2
22.3
22.4
22.5
22.6
22.7
22.8

Clinical Basics of Atopic Eczema: Synopsis
B. Przybilla, J. Ring, T. Ruzicka . . . . . . . . . .
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical Presentation . . . . . . . . . . . . . . . . . . .
Histopathology . . . . . . . . . . . . . . . . . . . . . . . .
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Complications . . . . . . . . . . . . . . . . . . . . . . . .
Associated Diseases . . . . . . . . . . . . . . . . . . . .
Psychosomatic Aspects . . . . . . . . . . . . . . . . .
Natural History . . . . . . . . . . . . . . . . . . . . . . .

II

Pathophysiology of Atopic Eczema

228

228
228
229
229
230
230
231
231

235
235
235
235
236
237
237
238
238
240
241
241
241

24

The Molecular Genetics of Atopy
W. Cookson . . . . . . . . . . . . . . . . . . . . . . . . . .
24.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
24.2 Candidate Genes . . . . . . . . . . . . . . . . . . . . . .
24.3 Genome Screens . . . . . . . . . . . . . . . . . . . . . . .

248
249
249
250

25

Genetics of Atopic Eczema
Young-Ae Lee, C. Söderhäll, U. Wahn . . . . . .
25.1 Genetic Epidemiology . . . . . . . . . . . . . . . . . . .
25.2 Approaches to the Genetic Analysis
of Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . .
25.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

255
255
256
262
263

26

Mechanisms of IgE-Regulation
M. Worm, T. Jakob . . . . . . . . . . . . . . . . . . . . . .
26.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
26.2 Mechanisms of Allergic Sensitization:
Allergen Uptake, Processing, and
Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . .

26.3 Activation, Migration, and Maturation
of Antigen-Presenting Cells . . . . . . . . . . . . . .
26.4 T Cell Activation and Polarization of the
T Cell Response . . . . . . . . . . . . . . . . . . . . . . . .
26.5 Origin and Maturation of B Cells . . . . . . . . . .
26.6 Immunoglobulins . . . . . . . . . . . . . . . . . . . . . . .
26.7 Isotype Switching . . . . . . . . . . . . . . . . . . . . . . .
26.8 Additional Factors of IgE Regulation . . . . . . .
26.9 Therapeutic Implications . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

265
265

265
266
267
269
270
270
271
272
273

27

23

Clinical Genetics of Atopic Eczema
F. Schultz Larsen . . . . . . . . . . . . . . . . . . . . . .

23.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
23.2 Methods for Mapping Complex Diseases . . .
23.3 Atopic Eczema/Dermatitis Syndrome . . . . .
23.4 Linkage Studies . . . . . . . . . . . . . . . . . . . . . . .
23.5 Statistics of Linkage Analysis . . . . . . . . . . . .
23.6 Candidate Gene . . . . . . . . . . . . . . . . . . . . . . .
23.7 Genome Screens in Atopic Eczema . . . . . . .
23.8 Candidate Genes in Atopic Eczema . . . . . . .
23.9 Other Chromosomes . . . . . . . . . . . . . . . . . . .
23.10 Maternal Effect and Genomic Imprinting . .
23.11 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

24.4 Single Gene Disorders . . . . . . . . . . . . . . . . . . .
24.5 Maternal Effects . . . . . . . . . . . . . . . . . . . . . . . .
24.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

244
244
244
245

Dendritic Cells in Atopic Eczema
T. Kopp, G. Stingl . . . . . . . . . . . . . . . . . . . . . . .
27.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
27.2 Antigen-Presenting Cell Subpopulations
in Atopic Eczema Skin . . . . . . . . . . . . . . . . . . .
27.3 Types of Antigen-Presenting Cells in
Peripheral Blood . . . . . . . . . . . . . . . . . . . . . . .

27.4 IgE-Facilitated Amplification of the
Immune Response . . . . . . . . . . . . . . . . . . . . . .
27.5 Role of Dendritic Cells in Initiating,
Maintaining, and/or Silencing the Allergic
Tissue Inflammation . . . . . . . . . . . . . . . . . . . .
27.6 Effects of Topical Calcineurin Inhibitors . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

275
275
275
278
279

281
282
282

28

Inflammatory Dendritic Epidermal Cells
A. Wollenberg . . . . . . . . . . . . . . . . . . . . . . . . . .
28.1 Langerhans Cells . . . . . . . . . . . . . . . . . . . . . . .
28.2 Inflammatory Dendritic Epidermal Cells . . .
28.3 Delineation of Inflammatory Dendritic
Epidermal Cells from Langerhans Cells . . . .

288
288
288

289


Contents

28.4 Ontogenesis of Inflammatory Dendritic
Epidermal Cells . . . . . . . . . . . . . . . . . . . . . . .
28.5 Inflammatory Dendritic Epidermal Cells
Are Present in Early Atopic Eczema
Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28.6 Inflammatory Dendritic Epidermal Cells
Are Present in Extrinsic and Intrinsic
Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . .
28.7 IgE-Receptor Expression of Inflammatory
Dendritic Epidermal Cells . . . . . . . . . . . . . .
28.8 In Situ Expression of Costimulatory
Molecules on Inflammatory Dendritic
Epidermal Cells . . . . . . . . . . . . . . . . . . . . . . .
28.9 Pinocytosis and Receptor-Mediated
Endocytosis of Epidermal Dendritic Cells
28.10 Diagnostic Epidermal Dendritic Cell
Phenotyping . . . . . . . . . . . . . . . . . . . . . . . . . .
28.11 Epidermal Dendritic Cells in Skin Lesions
Under Topical Therapy . . . . . . . . . . . . . . . . .
28.12 Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

32
290

290

290
290

291
291
292
292
293
293

29

Extrinsic and Intrinsic Atopic Eczema
N. Novak, T. Bieber . . . . . . . . . . . . . . . . . . . .
29.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
29.2 Allergic Atopic Eczema . . . . . . . . . . . . . . . . .
29.3 Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
29.4 The Role of Aeroallergens and Food
Allergens and the Atopy Patch Test . . . . . . .
29.5 The Role of Microbial Infections . . . . . . . . .
29.6 Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
29.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

296
296
296
297

299
300
300
301
301

30

Mast Cells in the Skin
M.K. Church . . . . . . . . . . . . . . . . . . . . . . . . . .
30.1 Mast Cell Activation . . . . . . . . . . . . . . . . . . .
30.2 Mast Cell Mediators . . . . . . . . . . . . . . . . . . . .
30.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

303
304
305
308
309

31

The Role of Eosinophils in Atopic Eczema
D. Simon . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
31.1 Evidence for Eosinophil Involvement
in Atopic Eczema . . . . . . . . . . . . . . . . . . . . . .
31.2 Mechanisms Causing Eosinophilia . . . . . . .
31.3 Activation of and Immunoregulation
by Eosinophils . . . . . . . . . . . . . . . . . . . . . . . .

31.4 Eosinophils as a Therapeutic Target . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

313
313
315
317
318
319

Role of T Cells in Atopic Eczema
M. Akdis, J. Verhagen, K. Blaser, C.A. Akdis
32.1 Skin-Selective Homing of T Cells . . . . . . . . . .
32.2 Mechanisms of Cutaneous LymphocyteAssociated Antigen Expression on Human
T Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
32.3 T Cell Chemotaxis in Atopic Eczema . . . . . . .
32.4 Role of IL-5 and IL-13 in Atopic Eczema . . . .
32.5 Role of Apoptosis in Allergic Inflammation
32.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

323
323

324
325
326
326
329
329

33

Keratinocytes in Atopic Eczema
G. Girolomoni, F. Mascia, C. Dattilo,
A. Giannetti, S. Pastore . . . . . . . . . . . . . . . . . .
33.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
33.2 Keratinocytes Actively Participate in the
Initiation and Amplification of Skin
Inflammatory Responses . . . . . . . . . . . . . . . . .
33.3 The Role of Keratinocytes in the Recruitment of Inflammatory Cells in Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33.4 Keratinocytes from Atopic Eczema
Patients Produce Increased Amounts of
GM-CSF and Other Proinflammatory
Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33.5 Dysregulated Activation of AP-1 Transcription Factors May Be Implicated in the
Enhanced Expression of Inflammatory
Genes by Atopic Eczema Keratinocytes . . . . .
33.6 Concluding Remarks . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

332
332

332

333

335

335
336
336

34

Inflammatory Mediators and Chemokines
in Atopic Eczema
B. Homey, T. Ruzicka . . . . . . . . . . . . . . . . . . . .
34.1 The Chemokine Superfamily . . . . . . . . . . . . .
34.2 Chemokine Receptors and TH1 and TH2 Cells
34.3 Memory T Cell Recruitment to the Skin . . . .
34.4 Dendritic Cell Trafficking . . . . . . . . . . . . . . . .
34.5 Eosinophil Recruitment . . . . . . . . . . . . . . . . .
34.6 Conclusion and Perspective . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
35
35.1
35.2
35.3
35.4

Cytokines in Atopic Dermatitis (Eczema)
H. Mizutani . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
Genetic Background and Cytokines . . . . . . . .
Th1 and Th2 Cytokines . . . . . . . . . . . . . . . . . .
Infiltrating Cells and Keratinocytes . . . . . . . .

340
340
342
342
344
345
346
346
350
350
350
350
351

XI


XII

Contents

35.5 Chronic Lesion and Fibrosis . . . . . . . . . . . . . .
35.6 Acquired Type Atopic Eczema/Innate
Type Atopic Eczema and IL-18 . . . . . . . . . . . .
35.7 Effects of Skin Lesions on Systemic
Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
35.8 Intrinsic and Extrinsic Atopic Eczema. . . . . .
35.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

352
352
353
353
354
354

36

Neuropeptides and Atopic Eczema
F. Fantini, C. Pincelli . . . . . . . . . . . . . . . . . . . .
36.1 Neuropeptides and the Skin . . . . . . . . . . . . . .
36.2 Role of Neuropeptides in Atopic Eczema . . . .
36.3 Neurotrophins and Atopic Eczema . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

357
357
358
359
360

37

Epidermal Lipids in Atopic Eczema
E. Proksch, R. Fölster-Holst, J.-M. Jensen . . .
37.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
37.2 Physiological Role of Lipids in the
Epidermis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
37.3 Abnormalities of Epidermal Lipids in

Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . . .
37.4 Impaired Ceramide Content and
Metabolism in Atopic Eczema . . . . . . . . . . . .
37.5 Ceramides Bound to Cornified Envelope
Proteins in Atopic Eczema . . . . . . . . . . . . . . .
37.6 Roles for Fatty Acids in Atopic Eczema . . . . .
37.7 Disturbed Epidermal Barrier Function
and Enhanced Skin Allergen Penetration
in Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . .
37.8 Lipids in the Treatment of Atopic Eczema . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

362
362
362
363
363
366
366

368
368
369

38

The Phenomenon of Irritable Skin
in Atopic Eczema
J. Huss-Marp, B. Eberlein-König, J. Ring . . . .
38.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .

38.2 Definition of Irritable Skin . . . . . . . . . . . . . . .
38.3 Quantification of Irritable Skin . . . . . . . . . . .
38.4 Definition of Irritable Skin in Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38.5 Clinical Evidence of Irritable Skin in
Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . . .
38.6 Experimental Evidence of Irritable Skin
in Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . .
38.7 Pathophysiology of Irritable Skin in Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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
40.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
40.2 Parallels to Allergic Disease . . . . . . . . . . . . . .
40.3 Atopy Patch Tests . . . . . . . . . . . . . . . . . . . . . . .

40.4 Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . .
40.5 Avoidance . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
40.6 The Relevance of Other Allergens . . . . . . . . .
40.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

390
390
391
391
392
394
395
396
396

41

Role of Food Allergy in Atopic Eczema
T. Werfel, K. Breuer . . . . . . . . . . . . . . . . . . . . .
41.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
41.2 Prevalence of Food Allergy in Atopic Eczema
41.3 Late Eczematous Reactions to Foods
in Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . .
41.4 Rate of Late Reactions to Challenges with
Foods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
41.5 Predictive Values of Diagnostic Tools . . . . . .
41.6 Allergen-Specific T Cell Responses in
Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . . .
41.7 Pollen-Associated Food Allergy in Atopic

Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

399
399
399
400
400
401
402
402
403

42

373
373
373
373
374
376

Staphylococcus Aureus and Atopic Eczema
M. Mempel . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42.1 Skin Colonization . . . . . . . . . . . . . . . . . . . . . . .
42.2 Mechanisms of Adherence . . . . . . . . . . . . . . .
42.3 Virulence Factors . . . . . . . . . . . . . . . . . . . . . . .
42.4 Concluding Remarks . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43

376

43.1
43.2

377
378
378

43.3
43.4

Animal Models of Atopic Eczema
A. Tanaka, H. Matsuda . . . . . . . . . . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
Spontaneous Animal Models for Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Inducible Animal Models of Atopic Eczema
Gene-operated Animal Models for Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

406
406
406
407
408
408
410
410

410
415
415


Contents

43.5 Final Remarks . . . . . . . . . . . . . . . . . . . . . . . . 415
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
44

Autoantibodies in Atopic Eczema
N. Mothes, I. Mittermann, K. Aichberger,
P. Valent, R. Valenta . . . . . . . . . . . . . . . . . . . .
44.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
44.2 Similarities and Cross-Reactivities Between
Environmental Allergens and Human
Proteins: The Concept of IgE Autoimmunity
is Reborn . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
44.3 The Discovery that the Occurrence of IgE
Autoantibodies Is Frequently Associated
with Atopic Eczema . . . . . . . . . . . . . . . . . . . .
44.4 Identification of IgE-Reactive Autoantigens
by Molecular Cloning . . . . . . . . . . . . . . . . . .
44.5 How Intracellular Antigens Can Contribute
to the Pathogenesis of Atopic Eczema . . . . .
44.6 IgE Autoreactivity as a Possible Marker for
Chronic Inflammation and Tissue Damage
in Atopic Eczema . . . . . . . . . . . . . . . . . . . . . .
44.7 IgG Autoantibodies in Atopic Eczema

Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
44.8 Pathomechanisms of IgE Autoreactivity . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
45

417
417

418

419
420
421

421
421
422
422

45.9
45.10
45.11

Pathophysiology of Atopic Eczema:
Synopsis
J. Ring, T. Ruzicka, B. Przybilla . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
Genetic Predisposition . . . . . . . . . . . . . . . . .
Disturbed Skin Barrier Function
(“Dry Skin”) . . . . . . . . . . . . . . . . . . . . . . . . . .

Itch as a Major Symptom of Eczema . . . . . .
Psychosomatic Interaction and Autonomic
Nervous System Dysregulation . . . . . . . . . .
Role of Allergy in Atopic Eczema . . . . . . . .
Role of IgE-Mediated Sensitization . . . . . . .
Role of Microbial Colonization and
Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Role of Contact Allergy . . . . . . . . . . . . . . . . .
Role of Irritants and Pollutants . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . .

III

Management of Patients with Atopy Eczema

45.1
45.2
45.3
45.4
45.5
45.6
45.7
45.8

46

426
426
426
427

427
427
428
428
428
429
429
429

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 . . . . . . . . . . . . . . . . . . . . . . . . .
46.3 Hereditary Factors . . . . . . . . . . . . . . . . . . . . . .
46.4 Nongenetic Factors . . . . . . . . . . . . . . . . . . . . .
46.5 The Domestic Environment . . . . . . . . . . . . . .
46.6 Possible Consequences for Prevention . . . . .
46.7 Primary Prevention . . . . . . . . . . . . . . . . . . . . .
46.8 Secondary Prevention . . . . . . . . . . . . . . . . . . .
46.9 Perspectives and Challenges . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

433
434
435
435
436

437
438
438
438

47

Role of Allergy Testing in Atopic Eczema
U. Darsow, J. Ring . . . . . . . . . . . . . . . . . . . . . . .
47.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
47.2 Food Allergy in Atopic Eczema . . . . . . . . . . .
47.3 Practical Approach to the Patient with
Suspected Food Allergy and AE . . . . . . . . . . .
47.4 Aeroallergens and Atopic Eczema . . . . . . . . .
47.5 Atopy Patch Test with Aeroallergens . . . . . . .
47.6 Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

441
441
441
442
443
444
446
447

48

Probiotics in Atopic Eczema

C. Schnopp . . . . . . . . . . . . . . . . . . . . . . . . . . . .
48.1 The Hygiene Hypothesis . . . . . . . . . . . . . . . . .
48.2 Primary Prevention Strategies in Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
48.3 Probiotics for Primary Prevention
in High-Risk Families . . . . . . . . . . . . . . . . . . .
48.4 Suggested Mechanisms . . . . . . . . . . . . . . . . . .
48.5 Remaining Questions . . . . . . . . . . . . . . . . . . . .
48.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

449
449
449
450
452
453
453
454

49

Measuring Disturbed Barrier Function
in Atopic Eczema
S. Seidenari, F. Giusti . . . . . . . . . . . . . . . . . . . .
49.1 Transepidermal Water Loss (TEWL) . . . . . . .
49.2 Skin Hydration and TEWL . . . . . . . . . . . . . . .
49.3 Skin Lipids and TEWL . . . . . . . . . . . . . . . . . . .
49.4 Reactivity to Irritants . . . . . . . . . . . . . . . . . . .
49.5 Barrier Function in Atopic Patients

Without Dermatitis . . . . . . . . . . . . . . . . . . . . .
49.6 TEWL and Topical Agents for Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50

456
456
457
458
458
459
459
460

Basic Topical Therapy with Emollients
in Atopic Eczema
W. Gehring . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
50.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 463

XIII


XIV

Contents

50.2 Amphiphilic Systems . . . . . . . . . . . . . . . . . . . .
50.3 Hydrophilic Systems . . . . . . . . . . . . . . . . . . . .
50.4 Desired Vehicle Effects: Hydration of the

Stratum Corneum and Induction of a
Diffusion Barrier Against Hydrophilic
Irritants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50.5 Modulation of Vehicle Effects by Glycerol
or Urea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50.6 Vehicle Influence upon Biologic Effect of
Topically Applied Drugs . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

464
465

54
466
466
466
467

51

Syndets in the Treatment of Atopic Eczema
O. Braun-Falco, H.C. Korting . . . . . . . . . . . . .
51.1 Cleansing of Eczematous Skin – The Scope
of the Problem . . . . . . . . . . . . . . . . . . . . . . . . .
51.2 The Development of Synthetic Detergents –
A Real Option . . . . . . . . . . . . . . . . . . . . . . . . . .
51.3 Desirable and Undesirable Effects of
Syndets on Human Skin – the Role of pH . . .
51.4 Syndets and Eczematous Skin – Clinical
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . .

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

468
468
469
471
474
474

52

Topical Treatment with Glucocorticoids
M. Kerscher, S. Williams, P. Lehmann . . . . . .
52.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
52.2 Mechanism of Action . . . . . . . . . . . . . . . . . . . .
52.3 Corticosteroid Classification . . . . . . . . . . . . .
52.4 Local and Systemic Unwanted Effects of
Topical Glucocorticoids . . . . . . . . . . . . . . . . . .
52.5 Influence of the Vehicle on the Effect of
Topical Corticosteroid Preparations . . . . . . .
52.6 Additional Active Ingredients in Topical
Corticosteroid Preparations . . . . . . . . . . . . . .
52.7 Acceptance of the Use of Topical
Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . .
52.8 Principles of Topical Treatment with
Corticosteroids in Atopic Eczema . . . . . . . . .
52.9 Topical Corticosteroids Versus Topical
Inhibitors of Calcineurin . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
53

53.1
53.2
53.3
53.4
53.5

Antimicrobial Therapy in Atopic Eczema
A. Gauger, J. Ring . . . . . . . . . . . . . . . . . . . . . . .
Antiseptic Therapy . . . . . . . . . . . . . . . . . . . . . .
Antibiotic Therapy . . . . . . . . . . . . . . . . . . . . . .
Nonantibiotic Therapy . . . . . . . . . . . . . . . . . .
Antimycotic Therapy . . . . . . . . . . . . . . . . . . . .
Antiviral Therapy . . . . . . . . . . . . . . . . . . . . . . .

53.6 Future Perspectives . . . . . . . . . . . . . . . . . . . . . 498
53.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499

477
477
478
480
482
484
485
486
487
488
489
492

492
493
495
496
497

Antihistamines in Atopic Eczema
T. Zuberbier . . . . . . . . . . . . . . . . . . . . . . . . . . .
54.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
54.2 First Generation Antihistamines . . . . . . . . . .
54.3 Second-Generation Antihistamines . . . . . . . .
54.4 Clinical Studies . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

503
503
503
504
504
505

55

Climatotherapy in Atopic Eczema
E. Vocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55.1 Influence of Climate on Atopic Eczema . . . . .
55.2 History of Climatotherapy . . . . . . . . . . . . . . .
55.3 Climate and Weather, Climate Adaptation . .
55.4 Human Biometeorological Research . . . . . . .
55.5 Basic Principles of Climatotherapy . . . . . . . .

55.6 Climatotherapy in Atopic Eczema . . . . . . . . .
55.7 Application of Climatotherapy . . . . . . . . . . . .
55.8 Therapy Results . . . . . . . . . . . . . . . . . . . . . . . .
55.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

507
507
508
511
512
513
513
516
517
520
520

56

Skin Care in Atopic Eczema
M. Kerscher, S. Williams . . . . . . . . . . . . . . . . .
56.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . .
56.2 General Recommendations . . . . . . . . . . . . . . .
56.3 Cleansing Sebostatic Skin in Atopic Eczema
56.4 Rehydrating Sebostatic Skin in Atopic Eczema
56.5 Decorative Cosmetic . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

524

524
525
526
528
531
531

57

Dietary Management of Atopic Eczema
C. Kugler . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
57.1 Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . .
57.2 Prevalence of Adverse Reaction to Food
in Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . .
57.3 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
57.4 Diagnostic Types of Diet . . . . . . . . . . . . . . . . .
57.5 Nutritional Recommendations When There
Is a Food Allergy . . . . . . . . . . . . . . . . . . . . . . .
57.6 Prognosis for Food Allergies . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
58

534
534
534
534
535
537
537
538

Phototherapy for Atopic Eczema
J. Krutmann, A. Morita . . . . . . . . . . . . . . . . . . 539
58.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
58.2 UVA1 Phototherapy for Acute, Severe
Atopic Eczema . . . . . . . . . . . . . . . . . . . . . . . . . 539


Contents

58.3 Phototherapy of Chronic, Moderate Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
58.4 Phototherapy of Atopic Hand and Foot
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
58.5 Mechanism of Action . . . . . . . . . . . . . . . . . .
58.6 Concluding Remarks . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

540
541
541
541
542

59

Atopic Eczema – Psychosomatic and
Psychobiological Aspects
U. Gieler . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
59.1 Introduction and Historical Aspects . . . . . .

59.2 Quality of Life in Atopic Eczema . . . . . . . . .
59.3 Psychological Aspects – Comorbidity
with Atopic Eczema . . . . . . . . . . . . . . . . . . . .
59.4 Stress and Atopic Eczema . . . . . . . . . . . . . . .
59.5 Psychoimmunology . . . . . . . . . . . . . . . . . . . .
59.6 Coping and Compliance in Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
59.7 Psychodynamic Aspects in Atopic
Eczema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
59.8 Family Aspects . . . . . . . . . . . . . . . . . . . . . . . .
59.9 Patient Management Programs . . . . . . . . . .
59.10 Measures to Influence the ItchScratch Cycle . . . . . . . . . . . . . . . . . . . . . . . . .
59.11 Measures to Reduce Negative Effects on
Social Relationships by Atopic Eczema
Prevention Programs . . . . . . . . . . . . . . . . . . .
59.12 Status of the Empirical Research Concerning Atopic Eczema Prevention Programs . .
59.13 The Psychological Training Program in
Atopic Eczema Prevention . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Phosphodiesterase 4 Inhibitors for
Atopic Eczema
L.F. Santamaria-Babi . . . . . . . . . . . . . . . . . . .
60.1 General Anti-inflammatory Effects
of PDE 4 Inhibitors . . . . . . . . . . . . . . . . . . . .
60.2 PDE 4 Inhibitors in Skin Inflammation . . .
60.3 Possible Effects of PDE 4 Inhibitors in
Different Phases of Atopic Eczema . . . . . . .
60.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

544
544
544
545
546
546
548
548
549
549
550

551
551
553
553

60

61

61.3 Skin and Psyche . . . . . . . . . . . . . . . . . . . . . . .
61.4 Use of Musical Components in Music
Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
61.5 Effect of Music on Humans: Conclusion . . .
61.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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 Immunomodulators . . . . . . . . . . . . . . . . . . . . . . . . . . . 574
62.13 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . 574
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574
63

558
558

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

568
568
568
569

62

557

559
561
561

567

63.1
63.2
63.3
63.4
63.5
63.6
63.7

Eczema School: Practical Approaches in
an Efficient Module of Tertiary Prevention

Programs
M. Premerlani, Y. Ludewig, C. Schnopp,
J. Ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
Eczema School at the Wolfgang Children’s
Hospital in Davos, Switzerland . . . . . . . . . .
Pedagogic Background of Eczema
Schooling . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction to Eczema School Sessions . .
Pedagogic Modules for the Main Part . . . . .
Pedagogic Methods for the Conclusion . . . .
Pedagogic Tools to Increase Self-Esteem
and Self-Respect . . . . . . . . . . . . . . . . . . . . . . .

576
576
577
578
578
578
579
579

XV


XVI

Contents

63.8 Organization of Eczema School . . . . . . . . . . 579
63.9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . 580
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 580
64

Unconventional Treatments
in Atopic Eczema
T. Schäfer . . . . . . . . . . . . . . . . . . . . . . . . . . . .
64.1 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . .
64.2 Usage in the General Population . . . . . . . . .
64.3 Usage of Complementary Alternative
Medicine for Atopic Eczema . . . . . . . . . . . . .
64.4 Utilization of Complementary Alternative
Medicine by Dermatologists . . . . . . . . . . . . .
64.5 Specific Complementary Alternative
Medicine Modalities . . . . . . . . . . . . . . . . . . .
64.6 Phytotherapy . . . . . . . . . . . . . . . . . . . . . . . . .
64.7 Chinese Herbal Medicine . . . . . . . . . . . . . . .
64.8 Acupuncture . . . . . . . . . . . . . . . . . . . . . . . . . .
64.9 Autologous Blood Therapy . . . . . . . . . . . . . .
64.10 Bioresonance . . . . . . . . . . . . . . . . . . . . . . . . .
64.11 Homoeopathy . . . . . . . . . . . . . . . . . . . . . . . . .
64.12 Massage Therapy and Aroma Therapy . . . .
64.13 Salt Baths . . . . . . . . . . . . . . . . . . . . . . . . . . . .
64.14 Vitamins and Minerals . . . . . . . . . . . . . . . . .
64.15 Harmful Effects . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

582
582

582
583

65

Alternative Medicine for Atopic Eczema:
A Comment
R. Happle . . . . . . . . . . . . . . . . . . . . . . . . . . . .
65.1 Romanticism . . . . . . . . . . . . . . . . . . . . . . . . .
65.2 Traditional Chinese Medicine Causing
Complete Renal Failure . . . . . . . . . . . . . . . . .
65.3 Acupuncture . . . . . . . . . . . . . . . . . . . . . . . . . .
65.4 Homeopathy . . . . . . . . . . . . . . . . . . . . . . . . . .
65.5 Alternative Medicine Will Always Exist . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
66

584
585
586
586
586
587
587
587
587
588
588
589
589

66.1
66.2
66.3
66.4
66.5
66.6
66.7
66.8
66.9
66.10
66.11
66.12

Therapy of Atopic Eczema: Synopsis
T. Ruzicka, S. Artik, J. Ring, B. Przybilla . . .
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . .
Skin Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Glucocorticoids . . . . . . . . . . . . . . . . . . . . . . .
Antihistamines . . . . . . . . . . . . . . . . . . . . . . . .
Anti-infectious Treatment . . . . . . . . . . . . . .
Ultraviolet Treatment . . . . . . . . . . . . . . . . . .
Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Environmental Control and Prevention . . .
Psychotherapeutic Approaches . . . . . . . . . .
Immunomodulators and Immunosuppressive Drugs . . . . . . . . . . . . . . . . . . . . .
Unconventional Therapy Options . . . . . . . .
Summary and Outlook . . . . . . . . . . . . . . . . .

592

592
592
593
593
594
594
596
596
597
598
598
599
599
600
601
602
602
603
603

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605


List of Contributors

Dr. Karl Aichberger
Division of Immunopathology, Department of Pathophysiology, 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

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. Mübeccel Akdis
Swiss Institute of Allergy and Asthma Research
(SIAF), Obere Str. 22, 7270 Davos, Switzerland

Prof. Dr. Dr. h.c. mult. Otto Braun-Falco
Dermatologische Klinik und Poliklinik, LudwigMaximilians-Universität, Frauenlobstr. 9 – 11,
80337 München, Germany

Dr. Susanne Artik
Klinik und Poliklinik für Dermatologie,
Heinrich-Heine-Universität, Moorenstr. 5,
40225 Düsseldorf, Germany

Dr. Kristine Breuer
Klinik und Poliklinik für Dermatologie und
Venerologie, Medizinische Hochschule Hannover,
Ricklinger Str. 5, 30449 Hannover, Germany

Dr. Carolyn Bauer

Klinik und Poliklinik für Dermatologie und
Allergologie, Ludwig-Maximilians-Universität,
Frauenlobstr. 9 – 11, 80337 München, Germany

Prof. Martin K. Church, PhD
Southampton General Hospital,
Dermatopharmacology, Level South Block,
Southampton, SO16 6YD, UK

Prof. Dr. Heidrun Behrendt
ZAUM-Zentrum Allergie und Umwelt,
Division Environmental Dermatology and Allergology,
Technische Universität München, Biedersteiner Str. 29,
80802 München, Germany

Prof. William Cookson
University of Oxford, Wellcome Trust Centre for Human
Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK

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

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


XVIII List of Contributors

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. 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. Manig´e Fartasch
Universitätsklinikum Erlangen, Hautklinik,
Hartmannstr. 14, 91052 Erlangen, Germany

Prof. Dr. Tari Haahtela
Department of Allergy, Skin and Allergy Hospital,
Helsinki University Central Hospital, P.O. Box 160,
00029, HUS, Finland

Prof. Andrew Y. Finlay
Department of Dermatology, University of Wales,
College of Medicine, Heath Park, Cardiff CF14 4XN,
UK

PD Dr. Eckhard Hamelmann

Department of Paediatric Pneumology and
Immunology, Charit´e, University Medicine Berlin,
Augustenburger Platz 1, 13353 Berlin, Germany

PD Dr. Regina Fölster-Holst
Universitäts-Hautklinik Kiel, Schittenhelmstr. 7,
24105 Kiel, Germany

Prof. Dr. Rudolf Happle
Klinik für Dermatologie und Allergologie, Klinikum
der Philipps-Universität, Deutschhausstr. 9,
35033 Marburg, 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. H. Hintner

St.-Johanns-Spital, Landesklinik für Dermatologie,
Müllner Hauptstr. 48, 5020 Salzburg, Austria
Prof. Dr. Bernhard Homey
Universitätsklinikum Düsseldorf, Heinrich-HeineUniversität, 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


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

XIX


XX

List of Contributors

Dr. R. Nickel
Department of Paediatric Pneumology and
Immunology, Charit´e, University Medicine Berlin,
Augustenburger Platz 1, 13353 Berlin, Germany

Prof. Dr. Dr. Johannes Ring
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München,
Biedersteiner Str. 29, 80802 München, Germany

PD Dr. Natalija Novak
Klinik und Poliklinik für Dermatologie,
Universitätskliniken Bonn, Sigmund-Freud-Str. 25,
53105 Bonn, Germany

Dr. Esther Ripphoff
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München,
Biedersteiner Str. 29, 80802 München, Germany

Dr. Saveria Pastore
Istituto Dermopatico dell’Immacolata, IRCCS,
Via dei Monti di Creta 104, 00167, Rome, Italy

Prof. Dr. Thomas Ruzicka
Klinik und Poliklinik für Dermatologie,
Heinrich-Heine-Universität, Moorenstrasse 5,
40225 Düsseldorf, Germany

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

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 Allergologie 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


List of Contributors

Prof. Dr. Georg Stingl
Universitätsklinik für Dermatologie, Immundermatologie und infektiöse Hauterkrankungen, Währinger
Gürtel 18 – 20, 1090 Wien, Austria

PD Dr. Dieter Vieluf

Zentrum für Dermatologie, Allergologie, Pädiatrie
und Umweltmedizin, Fachklinikum Borkum,
Jann-Berghaus-Str. 49, 26757 Borkum, Germany

Prof. Dr. Alain L. Ta¨ıeb
Pediatric Dermatology Unit and Department of
Dermatology, Centre Hˆopitalier Universitaire, Hˆopital
Saint-Andr´e, 1, rue Jean Burguet, 33075 Bordeaux
Cedex, France

Prof. Dr. Elisabeth Vocks
Klinik und Poliklinik für Dermatologie und
Allergologie am Biederstein, Technische Universität
München, Biedersteiner Str. 29, 80802 München,
Germany

Dr. Akane Tanaka
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

Prof Dr. Ulrich Wahn
Pediatric Pneumology and Immunology, Charit´e,
Campus Virchow-Klinikum, Augustenburger Platz 1,
13353 Berlin, Germany

Prof. Dr. Kristian Thestrup-Pedersen
King Faisal Specialist Hospital and Research Centre,
Dept. of Medicine, Section of Dermatology, MBC #46,

P.O.Box 3354, 11211 Riyadh, Saudi Arabia
G´erard Tilles
Soci´et´e fran¸caise d’histoire de la dermatologie,
Musee de l’hˆopital Saint-Louis, 1 av Claude Vellefaux,
75475 Paris cedex 10, France
Dr. Masami Uehara
Department of Dermatology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, 520 – 2192, Japan
Prof. Dr. Wolfgang Uter
Institut für Medizininformatik, Biometrie und
Epidemiologie, Friedrich-Alexander-Universität
Erlangen-Nürnberg, Waldstr. 6, 91054 Erlangen,
Germany
Prof. Dr. Peter Valent
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. Rudolf Valenta
Center for Physiology and Pathophysiology, Dept. of
Pathophysiology, Div. of Immunopathology, Vienna
General Hospital, University of Vienna, Währinger
Gürtel 18 – 20, 1090 Vienna, Austria
Dr. Johan Verhagen
Swiss Institute of Allergy and Asthma Research
(SIAF), Obere Str. 22, 7270 Davos, Switzerland

Prof. Dr. Daniel Wallach
Department of Dermatology, Hˆopital Tarnier,
89, rue d’Assas, 75006 Paris, France
PD Dr. Bettina Wedi

Dept. of Dermatology and Allergology, Hannover
Medical University, Ricklinger Str. 5, 30449 Hannover,
Germany
Dr. S. Weidinger
Klinik und Poliklinik für Dermatologie und
Allergologie am Biederstein, Technische Universität
München, Biedersteiner Str. 29, 80802 München,
Germany
Prof. Dr. Thomas Werfel
Klinik und Poliklinik für Dermatologie und
Venerologie, Medizinische Hochschule Hannover,
Ricklinger Str. 5, 30449 Hannover, Germany
Dr. Stefanie Williams
Universität Hamburg, Fachbereich Chemie, von Melle
Park 8, 20146 Hamburg, Germany
PD Dr. Andreas Wollenberg
Klinik und Poliklinik für Dermatologie und
Allergologie, Ludwig-Maximilians-Universität,
Frauenlobstr. 9 – 11, 80337 München, Germany
Judith A. Woodfolk, MD, PhD
Division of Allergy & Immunology, University of
Virginia, P.O. Box 801355, Charlottesville, VA 22908,
USA
Prof. Dr. Margitta Worm
Department of Dermatology and Allergy, Charit´e,
University Medicine Berlin, Schumannstr. 20/21,
10117 Berlin, Germany

XXI

XXII

List of Contributors

Prof. Dr. Brunello Wüthrich
Spital Zollikerberg, Toichtenhauserstr. 20,
8125 Zollikerberg, Switzerland
Prof. Dr. Torsten Zuberbier
Department of Dermatology and Allergy, Allergy
Centre Charit´e, University Medicine Berlin,
Schumannstr. 20/21, 10117 Berlin, Germany


I Clinical Aspects of Atopic Eczema



Chapter 1

Atopy: Condition, Disease, or Syndrome?

1

J. Ring

1.1
History
The term “atopy” is relatively new, although it is
derived from the ancient Greek. The American allergists Coca and Cooke [10] wanted to describe a strange,

abnormal type of hypersensitivity against environmental substances which was observed only in humans
and tended to occur within families without obvious
prior sensitization. They wanted to differentiate this
type of hypersensitivity from other forms such as anaphylaxis [11] and asked the philologist Perry from
Columbia University for help. This is in contrast to
many other famous physicians who felt confident
enough to create their own words from ancient languages, sometimes linguistically not very correct but
successful. For example, the term “anaphylaxis,” referring to a lack of protection, should have been in correct
Greek “aphylaxis” [40]. However, for reasons of rhythm
or from a lack of knowledge of Greek, Richet, who later
won the Nobel prize, preferred “anaphylaxis” [37]. Perry came up with the term “atopy,” meaning “not in the
right place” or “strange” [10].
Since that time more than 80 years have passed. Yet
the term “atopy” is still controversial [2, 3, 23, 40].
Nonetheless, the clinical conditions described by this
name are old and have been well known for thousands
of years. This is clear from classical medical literature
where we find descriptions of asthma, eczema, and rhinitis (catarrh) [2, 43]. Similar descriptions can be found
in Chinese medical literature from the Sui dynasty
(581 – 618 A.D.), i.e., On Etiologies of Diseases by Chao
Yuan Fang, volumes 35 – 50 (K. Kang and J. Hanifin,
personal communication). Huang Ti described a disease with “noisy breathing” already in 2698 B.C.
The first documented atopic individual was most
likely Emperor Octavianus Augustus, who suffered

from extremely itchy skin, seasonal rhinitis, and tightness of the chest (Suetonius: Vita Caesarum) [39]. His
grandson, Emperor Claudius, suffered from symptoms
of rhinoconjunctivitis. Including Augustus’s great
grandnephew, Britannicus, who supposedly suffered
from horse dander allergy, one can safely state that the

first family history of atopy is documented in the JuliTable 1.1. Historical milestones in elucidating the etiopathophysiology of atopy
Observation

Investigator(s)

Date

Pollen skin and provocation test
Mast cell
Neurodermite diffuse
Prurigo diath´esique
Patch test
Anaphylaxis
Allergy
Histamine
Hyposensitization
Transferable hypersensitivity
Atopy
Reagins in atopy
Allergic diathesis
Bronchial hyperreactivity
Shock fragment
Cortisone
First placebo-controlled
immunotherapy trial
Vegetative dysregulation
Genetic basis
Type I reaction
Immunoglobulin E

Blackley

1873

Ehrlich
Brocq
Besnier
J. Jadassohn
Richet, Portier
von Pirquet
Dale, Laidlaw
Noon and Freeman
Prausnitz and Küstner

1877
1891
1892
1895
1902
1906
1910
1911
1921

Coca, Cooke
Coca, Groove
Kämmerer
Tiffeneau
Hansen
Hench, Kendall

Frankland

1923
1925
1928
1945
1941
1949
1954

Korting
Schnyder
Coombs, Gell
Ishizaka K. and T.
Johansson
Vorhoorst
Szentivanyi
Metzger
Mossmann
Coffmann

1954
1960
1963
1966
1967
1967
1968
1977
1987

1988

House dust mites
Beta blockade
Fc 5 receptor I
Th1–Th2 concept
Interleukin 4