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 Library of Congress Control Number: 2005926887 This work is subject to copyright All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag Violations are liable to prosecution under the German Copyright Law Springer-Verlag Berlin Heidelberg New York Springer is a part of Springer Science+Business Media http://www.springeronline.com ˇ Springer-Verlag Berlin Heidelberg 2006 Printed in Germany The use of general descriptive names, registered names, trademarks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use Product liability: The publishers cannot guarantee the accuracy of any information about the application of operative techniques and medications contained in this book In every individual case the user must check such information by consulting the relevant literature Editor: Gabriele Schröder Assoc Editor: Marion Philipp Desk Editor: Ellen Blasig Production Editor: Joachim W Schmidt Cover design: eStudio Calamar, Spain Typesetting: FotoSatz Pfeifer GmbH, D-82166 Gräfelfing Printed on acid-free paper – 24/3150 – 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 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 7 The History of Atopic Eczema/Dermatitis A Taăeb, 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 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 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 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 Atopic Eczema in Infants A Taăeb, 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 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 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 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 66.6 Ultraviolet Treatment 66.5 Anti-infectious Treatment Colonization and impetiginization of eczematous skin with Staphylococcus aureus or other infectious agents represent an important provoking factor in AE (see Chap 42) When indicated, appropriate antimicrobial treatment should be instituted Deliberate, general use of antimicrobials may not be recommended due to the emergence of resistant organisms and the sensitizing potential of many antibiotic preparations 66.5.1 Antibiotic Therapy Bacterial infection of the skin, often caused by superantigen-producing staphylococci, has to be treated with antibiotics topically or systemically, especially if impetiginization is clinically evident Antibacterial therapy leads not only to reduction of bacterial colonization, but in many cases to improvement of AE Fusidic acid seems to be the antibiotic drug of choice due to its inhibition of staphylococci at very low concentrations, although increasing resistance of fusidic acid has been noted in some areas Erythromycin (1 % – %) provides another successful therapy option For topical treatment of the nasal cavity, mupirocin ointment is recommended Generalized impetiginized AE can successfully be treated with macrolides, e.g., erythromycin, azithromycin, clarithromycin, or roxithromycin Antibiotics with an inhibitory effect on protein synthesis can suppress the production of superantigens from S aureus (staphylococcal enterotoxin) For macrolide-resistant S aureus, penicillinase-resistant penicillins and firstgeneration cephalosporins should be used 66.5.2 Antibiotic–Steroid Combination Therapy When T cells are stimulated with superantigens, they become insensitive to glucocorticoids [14] Thus, reduction of S aureus superantigen production and augmentation of corticoid sensitivity by antibiotics leads to an effective combined antibiotic-topical glucocorticoid therapy, allowing the use of low- to mediumpotency topical corticosteroids to achieve the same clinical effects as high-potency corticosteroids when used alone (see Chap 42, 53) 66.5.3 Antimycotic, Antiviral, and Antiseptic Therapy Patients with predominantly head and neck involvement or proven hypersensitivity to Pityrosporum ovale should be treated with azole derivatives In addition to its antimycotic properties, anti-inflammatory and antibacterial effects by topical ketoconazole have been demonstrated Only in case of marked involvement of the head-and-neck area or unresponsiveness to standard topical treatment, are systemic antimycotics recommended In case of eczema herpeticum – due to the danger of virus dissemination with possible multisystemic involvement (pneumonia, encephalitis) – a fast, systemic antiviral therapy is needed (see Chap 53) Triclosan, povidone-iodine, and octenidine are antiseptics with good to excellent antibacterial/antimicrobial activity Furthermore, silver-coated textiles provide antibacterial/antimicrobial properties and are not yet associated with drug resistance (see Chap 53) 66.6 Ultraviolet Treatment Many patients experience improvement of AE by sun exposure Although this may be due to a number of circumstantial factors, numerous reports have shown that phototherapy is effective in acute exacerbated as well as in chronic moderate AE (see Chap 58) While broadband UVB and psoralen UVA (PUVA) have been the mainstay of phototherapy for some time, new phototherapeutic modalities, including UVA1 and narrowband 311-nm UVB have been introduced in the past several years The best modality and mode of use depends on the type and severity of AE However, when considering UV treatment in an individual patient, the possibility of UV-sensitive eczema or light-provoked dermatological diseases should be kept in mind 66.6.1 UVA1 In case of acute, severe exacerbations of AE, high-dose UVA (UVA1, 340 – 400 nm) monotherapy has proven to be effective and to be superior to UVA–UVB therapy Inhibition of Langerhans cell migration out of the epi- 599 600 66 Therapy of Atopic Eczema: Synopsis dermis and particularly reduction of the relative numbers of IgE + intraepidermal Langerhans cells (typically found in AE), as well as reduction of IgE-bearing Langerhans cells and mast cells in the dermis, seem to play an important role for the significant clinical improvement of AE and reduced pruritus by high-dose UVA1 irradiation Additionally, downregulation of IFN- * expression and apoptotic effects in skin infiltrating T cells are induced resulting in reduction of the inflammatory infiltrate Both high-dose and medium-dose UVA1 have been proven to be well tolerated and effective [39] However, early relapses within months have been described in many patients, especially with the medium doses [1, 39] In addition, careful indication for treatment is required, and UVA1 irradiation 10 – 15 times, twice a year, should not be exceeded, as its long-term safety with regard to skin carcinogenesis including melanoma induction, particularly in children, and photoaging, is not yet finally established Therefore, in severe, acute exacerbated AE, a treatment regimen involving an initial high-dose UVA1 therapy with 10 – 15 applications, which is switched to UVB-311 irradiation, is preferable, aiming at an effective maintenance therapy with low side effect potential 66.6.2 UVB-311 In chronic, moderate AE, good clinical results are obtained with UVB-311 irradiation, which inhibits the expression of ICAM-1 Phototherapy should be combined with other treatment modalities, e.g., glucocorticoids, to achieve a steroid-sparing effect, and these positive results are maintained even after termination of therapy Stabilization of glucocorticoid- or UVA1induced remission is observed 66.6.3 PUVA In severe cases, PUVA treatment is another therapeutic option By induction of psoralen-DNA-strand bridges, epidermal DNA synthesis is inhibited In addition, direct bacteriostatic effects by reduction of the number of S aureus have been reported for PUVA Despite its indisputable efficacy, indication for PUVA therapy should be carefully considered because of disadvantages such as nausea, increased risk of skin cancer, and initial exacerbation of eczema if not combined with glucocorticoids Moreover, the required number of treatment sessions is quite high, and prolonged maintenance therapy is often necessary Once PUVA has been performed, further therapy with cyclosporin is restricted due to enhanced risk of carcinogenicity Alternatively, especially if hands and feet are involved, cream or bath-PUVA are another treatment option with a low side effect profile (lack of nausea and stomach pain, no need of wearing PUVA glasses, only short duration of light sensitivity) 66.6.4 Extracorporal Photopheresis Good clinical results (accompanied by reduction of IgE and ECP levels) have been obtained with extracorporal photochemotherapy in severe cases of AE, resistant to other therapies [1, 34] 66.7 Diet Generally, two types of diets can be distinguished in the management of AE: elimination diets based on food intolerance and supplementation diets based on a deficiency (see Chaps 41, 57) For about 10 % – 15 % of infants, but only in rare cases in older children or adults, a dietary intervention seems to be effective However, the exacerbation of AE by food allergens must be probable enough This may be rather difficult to demonstrate: positive allergy tests must be critically interpreted by physicians experienced in allergy tests, as they often only reflect a stimulated polyclonal IgE-synthesis without clinical relevance Thus, elimination of a large number of foods, only based on positive skin tests (skin prick test and atopy patch test) and radio-allergosorbent test (RAST) results, is often ineffective and harmful In line with this, the long-term value of elimination of test-positive allergens has been questioned since the clinical benefit could not be maintained during a 1-year follow-up treatment Moreover, around 10 % of positive doubleblind placebo-controlled food challenge (DBPCFC) results are not IgE-mediated Due to the poor reliability of these tests, suspicion of food-related symptoms should be the indication for DBPCFC, the gold standard in the diagnostic work-up of food allergy 66.8 Environmental Control and Prevention A diet should not bear the risk of decreased psychological and social well-being of the patient and compromise the quality of life more than AE itself, and might even worsen AE as a trigger factor causing additional stress Moreover, the diet should not disrupt the normal life of the patient and his family and thus cause psychological problems as a replacement for the allergological ones However, not only psychosocial consequences, but also medical risks and dangers of a diet, i.e., hypovitaminosis, weight loss, calcium deficiency and rickets, and other malnutrition states must be taken into account Thus, the assumption by the public that restrictive diets are harmless is naive The critical and considerate use of dietary measures is nevertheless justified under the following circumstances: The allergic reaction toward a food allergen is severe enough and thus quality of life markedly reduced The allergen must be easily avoidable The patient or his parents must be mentally capable to permanently follow the dietary regimen Until now there has been no generally favored type of diet for all patients with AE Because of the above-mentioned diagnostic problems in food allergy testing, most patients should be offered an empirical elimination diet first [30], avoiding the frequent allergens of cow’s milk, hen’s egg, wheat, and soy in infants and pollen-related foods such as nuts, fruit, and vegetables in adolescents and adults, (but considering the supplementation of essential nutrients) If there is a specific suspicion that one or more food triggers an allergy for a patient, a so-called specific elimination diet (e.g., avoiding cow’s milk) is carried out Babies are given a compatible formula feed, e.g., extensively hydrolyzed formula or a formula made of an amino acid mixture In the case of a nonspecific suspicion and unresponsiveness to empirical elimination diets, an oligoantigenic diet can be carried out, using foods that rarely trigger allergies in the corresponding age group and have not been conspicuous in the patient’s history Besides nutritional allergens, irritating foods such as citrus fruits and biogenic amines should be avoided Contrary to general belief, food dyes and preservatives are rare trigger factors, particularly in adults After year of consistently avoiding the noncompatible food, there must be retesting to establish the current clinical status Studies have demonstrated the dis- appearance of food allergy symptoms in up to onethird of children and adults in – years, although positive skin tests and positive serum IgE levels may persist Evidence suggests that the probability of outgrowing a food allergy depends on the food allergen and the patient’s compliance with the elimination diet Allergies to peanut, nuts, fish, and other seafood appear to be more persistent Several studies have shown that in contrast to elimination diets, supplementation with essential (either n-6 or n-3) fatty acids is not beneficial in AE (see Chaps 37, 57) 66.8 Environmental Control and Prevention Environmental control is aimed at the elimination of flare factors responsible for the provocation and exacerbation of AE in a genetically predisposed individual Numerous measures can be summarized, which must be individualized for each patient These include elimination of irritating clothing, e.g., wool; elimination of allergenic foods; elimination of house dust mites by appropriate housing conditions, usage of acaricides and impermeable sheets (encasing); reduction of furred pet contacts (questioned at the moment), especially during the first years of life; elimination of contact allergens (or oral tolerance induction!), irritants, and substances causing contact urticaria from the household and occupation; occupational counseling regarding the choice or a change of occupation and work protection; hospitalization; climatotherapy at high altitude or the seaside (see Chap 55); and elimination of stress (family, occupation) In cases where elimination of inhalation allergens is not possible, specific immunotherapy is recommended (see Chap 46) Prevention of AE can be accomplished at various stages: In the prenatal phase, reduction of maternal smoking reduces the risk of allergy Recent studies on breast-feeding and atopy showed conflicting results with regard to effective prevention of the disease Exclusive feeding of hypoallergenic, i.e., hydrolyzed milk or amino-acid-based formula, in the first months of life has a protective effect in terms of development of AE in the first years of life, compared to feeding with cow’s milk formula Passive smoking in young children is associated with increased risk of allergic diseases (see Chap 39) 601 602 66 Therapy of Atopic Eczema: Synopsis A promising strategy for primary prevention is provided by probiotics, i.e., bacterial strains of healthy gut microflora exerting potentially beneficial effects such as Bifidobacterium lactis and lactobacillus GG, which are increasingly replaced by a variety of hospital-acquired organisms in early gut microflora Probiotics have been proven to be beneficial if given to the pregnant mother and later to the newborn child for months: the incidence of AE in the probiotic group was approximately half that of the placebo group at the age of and years The positive, immunomodulating effect was explained by oral tolerance induction to dietary antigens and to commensal microflora (anergy, production of regulatory T cells, increase of IL-10 and TGF- q ), by shifting from the Th-2 to Th-1 immune response pattern (after binding of microbial compounds by TLR2, TLR4, and TLR9), increasing IgA responses, normalization of increased intestinal permeability in patients with AE, and degradation of food allergens 66.9 Psychotherapeutic Approaches The psychosomatic interplay in AE is a self-evident phenomenon to every physician involved in the management of patients with this disease The influence of psychological factors thus requires education and stabilization of patients and family members In selected patients, psychotherapeutic treatment and family or group therapy, (and/or use of sedative drugs which additionally exert antihistamine effects) may be needed Behavioral treatment and autogenous training may be directed at scratching reduction (see Chaps 59, 61, 63) 66.10 Immunomodulators and Immunosuppressive Drugs The pathophysiology of AE is characterized by both immunodeficiency and exaggerated immune responses Despite a sound rationale (inhibition of IgE production in vitro), the use of immunomodulators such as IFN- * has met with limited success at best Therefore, current interest concentrates on the use of immunosuppressive agents The prototype drug cyclosporin A leads to rapid remission of signs and symptoms of severe, therapy- resistant AE [44] by blocking T cells that were already activated, thus reducing IgE synthesis Drug interactions and exclusion of patients with risk factors have to be considered: The combination of UV treatment with cyclosporin is prohibited due to an increased risk of photocarcinogenesis The introduction of cyclosporin can be regarded as a breakthrough in the treatment of severe AE, and its efficacy and safety have been demonstrated in children By blocking the proliferative responses of T and B lymphocytes (an increase in IFN* and a decrease in IL-10), oral mycophenolate mofetil has proven to be another effective and well-tolerated drug for treating severe AE, with no serious adverse effects Various topical immunomodulators (TIMs) with a cyclosporin-like mechanism of action and improved topical efficacy are currently in clinical development, as cyclosporin by itself is not efficient in topical treatment Most experience has been accumulated with the calcineurin inhibitors tacrolimus (FK-506) and pimecrolimus, which acts in the same way since it is more lipophilic Tacrolimus (tsukuba, macrolide, and immunosuppression), originally extracted from the fermentation broth of the Japanese soil bacterium Streptomyces tsukubaensis in 1984, has been found to be 10 – 100 times more potent than cyclosporin and to penetrate the skin much better due to its lower molecular weight Several multicenter studies with short-term (3 weeks) and long-term therapy (up to year) with tacrolimus ointment 0.03 % in children older than years and 0.1 % in adults) and % pimecrolimus (3 months and older) have proven high efficacy, leading to marked improvement with rapid clearing of eczematous skin lesions and pruritus as well as safety in adults and children No relevant systemic adverse effects and no increased incidence of cutaneous infections have been observed [35] There is no indication that the effectiveness of TIMs decrease over time Long-term use of TIMs is well tolerated, leading to reduction of eczema flare-ups, with no rebound effect but able to replace or reduce corticosteroids TIMs are effective on all skin sites Preferentially in vulnerable areas such as the face, neck and eyelids, where glucocorticoids should not be given for more than weeks due to glucocorticoid withdrawal dermatitis, atrophy or telangiectasia, TIMs are the therapy of first choice A transient burning sensation at the site of application is the most frequent local side effect However, this local 66.12 Summary and Outlook irritation is most severe during the 1st week of treatment and ameliorates within a few days TIMs have neither phototoxic nor photoallergenic potency, and no effects on collagen synthesis and skin thickness were observed Exposure to natural or artificial sunlight has to be kept at a minimum during therapy as the risk of photocarcinogenicity cannot definitely be excluded at this point in time (see Chap 62) In moderate to severe AE, tacrolimus ointment (0.03 % for over 2-year-old and below 16-year-old children; 0.1 % for adults), in cases of weak to moderate AE, pimecrolimus cream % should be applied until complete remission is achieved; therapy should be restarted at an early stage whenever new lesions occur Pharmacological interventions into the disturbed phosphodiesterase-cyclic adenosine monophosphate system, e.g., by phosphodiesterase inhibitors (see Chap 60) may also correct immunopharmacological abnormalities of AE 66.11 Unconventional Therapy Options Unconventional therapy options (UTOs), including, for example, phytotherapy, acupuncture, bioresonance, autologous blood injection, and homeopathy, may be defined as forms of therapy that involve any treatment method without scientific proof of adequate or superior efficacy compared to conventional treatment In many countries, UTOs are attracting increasing attention in the mass media and especially among patients who are more depressive and have greater disease-specific stress However, serious adverse effects might occur, especially after intake of Chinese herbal medicine, usually consisting of ten different herbs: several investigators reported cases of hypersensitivity reactions, hepatoand nephrotoxicity including carcinoma of the urinary tract, agranulocytosis, cardiomyopathy, and respiratory distress syndrome with cases of lethal outcome The view held by many patients that “natural” therapy is harmless and has no adverse effects is thus a misconception (see Chaps 64, 65) 66.12 Summary and Outlook Symptomatic therapy in AE must be individualized and the multifactorial pathogenesis of the disease must be considered Individual flare factors should be eliminated whenever possible A breakthrough in the therapy of AE and thus patients’ quality of life has been achieved in the last few years by the introduction of TIMs, which are, even when applied for weeks and months, efficient, safe, and well tolerated Other beneficial treatment options are provided by UVA1 and UVB-311 irradiation and antimicrobial therapy including anti-staphylococcal antibiotics, preferably in combination with the new generation of topical glucocorticoids The latter are still indispensable due to their rapid onset of clinical efficacy and the availability of a variety of different vehicle preparations, also allowing treatment in certain areas such as the scalp and intertriginous areas Replacement of naturally occurring, antimicrobial defensive agents, which are diminished in AE, e.g., sphingosine, human q defensin (HBD)-2 and HBD-3, are possible therapeutic options for the future Furthermore, probiotics appear to be a promising strategy for primary prevention of AE The change of paradigm for allergy prevention from the avoidance of risk factors to the active induction of tolerance may in future reverse the epidemiologic trends of the past decades At the moment, eczema school programs have shown to improve the skin condition and the quality of life of AE patients (see Chap 63) 603 Subject Index acanthosis 78, 218, 229, 352 Acarus siro var hominis 123 acid ceramidase 161 acidic syndet 474 acquired immunodeficiency syndrome (AIDS) 202 acrodermatitis enteropathica 104 activation-induced T cell death (AICD) 326 activator protein 332 – (AP-1) 336 acupuncture 586, 592 adenosintriphosphate 530 adhesin 406 adrenal cortical hormone 477, 488 aeroallergen 54, 59, 296, 299, 395, 443, 507, 513 agglutination test 407 aggravating factors 57 aggression 548 AIDS 123, 202 air – pollen concentration 512 – pollution 27, 507, 513 airway – eosinophilia 110 – hyperresponsiveness (AHR) 325, 346 alkaline 473 allergen 332 – allergen-specific immunotherapy 438 – exposure 435 – sensitization 153 allergic – asthma 230 – conjunctivitis 125 – contact dermatitis (ACD) 168, 178, 484 – inflammation, apoptosis 326 – rhinoconjunctivitis, see also hay fever 4, 230, 434 – shiners 68 – tissue inflammation 281 allergy testing 58 – aeroallergens 59 – contact allergens 58 – food allergens 58 alloknesis 223 alopecia areata 131 alpha-hemolysin 407 alpha-pinene 385 Alternaria 396 amino acid 479 – exchange 258 – sequence 340 – solution 54 amphiphilic emulsion 464 amyloidosis 133 anaphylaxis angiotensin-converting enzyme 307 anhidrotic congenital ectodermal dysplasia (ACED) 129 animal model 261, 410 ankylosing spondylitis 146 anorexia nervosa 162 antecubital eczema 38 antibacterial – silver coated textile 496 – therapy 599 anticyclones 511 antigen – antigen-presenting cell (APC) 208, 218, 265, 269, 282 – exposure 450 – uptake 266 antihistamine 110, 153, 226, 272, 598 anti-inflammatory drug 459 anti-ovalbumin 387 antipruritics 226 antiseptics 495, 599 anti-staphylococcal therapy 493 anxiety 32, 545, 548, 552 apolar emulsion 463 apoptosis 326, 421 apron sign 167 Arabidopsis thaliana 420 aristolochic acid 592 aroma therapy 587 Aspergillus 396 – fumigatus 418 astemizole 497 asthma, see also bronchial asthma 4, 108, 151, 152, 246, 391 – in adults 111 – in children 111 – risk factors 109 asthmatic wheezing 434 ataxia teleangiectatica 209 atopic – airway disease 511 – dermatitis – – descendant family history 215 – – maternal effect 215 – – paternal effect 215 – eczema – – after childhood 150 – – asthma 151 – – climate 507 – – community samples 150 – – comorbidity 545 – – diagnostic criteria 21, 90 – – differential diagnosis 95, 100 – – discoid variant 87 – – eczematous skin 218 – – extrinsic/intrinsic subtypes 24 – – family history 213 – – follicular form 80, 81 – – follicular variant 86 – – frequency in adults 22 – – frequency in children 22 – – hay fever 151 – – in childhood 86 – – intrinsic type 154 – – intrinsic/non-IgE-associated type 81 – – irritant exposure 171 – – nummular type 87 – – occupational guidelines 175 – – papular lichenoid variant 86, 87 – – papulous type 37 – – parental predisposition 24 – – phases 228 – – pollen-sensitive 24 – – prevalence 22 606 Subject Index – – prevention 552, 601 – – prognostic factors 27 – – prurigo type 87 – – risk factors 24 – – sick leave 170 – – topical therapy 463 – – treatment 18, 451 – eyelid eczema 74 – family history 213 – feet 76 – hand eczema 88, 166, 167 – manifestation 433 – march 108, 151, 433 – respiratory disease – – personal history 214 – skin diathesis 168, 173 – winter feet 41, 76, 77, 88 atopiform dermatitis 203 atopy – definition 84 – etiopathophysiology – features 61 – patch test (APT) 97, 182, 275, 281, 392, 396, 428, 443, 444 – stigmata 70 autoantigen 351 autogenic training 550 autoimmune disease 133 autologous blood therapy 587 autonomic nervous system 427 axon 357 – reflex experimental model 358 azole derivative 599 B cell 269, 271, 288, 412 B lymphocyte 269 bacterial – antigen 351 – infection 115, 436, 599 bacteriology 16 Bacterium prodigiosum 471 Bacteroides vulgatus 452 bamboo hair 103 barrier – disruption 183 – dysfunction 368 – function 183 – homeostasis 332 basidiomycete 446 basophils 279, 352, 392 beclomethasone dipropionate 110, 111 Behcet’s disease 304 Besnier’s prurigo 13 beta-adrenergic blockade 17 beta-hemolytic streptococcus 118 betamethasone 572 Bifidobacterium 450 bioengineering 392 bioresonance 587 Birbeck granule 288, 289, 394 birch pollen allergy 403, 418 – birch-pollen-related food 402 blepharoconjunctivitis 125 blood eosinophilia 109, 313 bone marrow 315 – transplantation 350 Bowenoid papulosis 122 brain-derived neurotrophic factor (BDNF) 359 breast feeding 26, 47, 437, 449 Brocq’s theory 14 bronchial – asthma 5, 317 – – eosinophilic inflammation 108 – hyperresponsiveness (BHR) 108, 318 – – risk factors 109 Buckley’s syndrome 207 budesonide 111 bufexamac 181, 231 bullous impetigo 116 burning sensation 573 C fiber 222, 305, 427 C type lectin family 266 calcineurin 489 – inhibitor 282 calcitonin gene-related peptide fibers (CGRP) 219, 357 calcium chlorid 161 calcium-binding protein 420 Candida albicans 117, 128, 300 candidate gene 237, 238, 244, 256, 260, 434 – study 259 candidiasis 101 carboxypeptidase 307 carcinogenicity 600 Caspase-I 185 cataract 126 cathepsin G 307 C-C chemokine 219, 240 cedar pollen pollinosis 410 cefuroxime 494 cephalosporin 484 ceramides 363, 366, 376, 414, 458, 530 cetirizine 154, 504, 505 cheilitis 37, 75, 89 chemical peeling 161 chemokines 185, 187, 282, 318, 334, 340 – superfamily 340 childhood eczema 39 Children’s Dermatology Life Quality Index (CDLQI) 33 Children’s Life Quality Index (CLQI) 33 Chinese herbal medicine 586, 592, 603 chlorhexidine 492 chlorine 528 chlorpheniramine 503 cholesterol 458 – sulfate 362 chromametry 392 chromatin 313 chromosome – 1q21 247, 297 – 3q21 247, 261 – 5q 426 – 5q31.33 257 – 5q34 245 – 11q13 245 – 17q25 247 – 20p 248 – region 238 – segment 5q31–32 239 – Xp23 259 chronic – granulomatous disease (CGD) 207, 209 – inflammatory skin disease 100 – obstructive pulmonary disease (COPD) 382 – vesicular dyshidrotic hand eczema 541 chymase 307, 352 chymotrypsin-like enzyme 159 ciliary dyskinesia 382 cilomilast 558 cipamfylline 558 Cladosporium 395 Claudine family 184 cleansing agent 526 climate 511 – chamber 382 climatic adaptation 511 climatotherapy 508, 513, 516 clinical – assessment 21 – manifestation 62 cluster chemokine 341 coeliac disease 127 cold cream 530 cold-pressure test 547 common variable immunodeficiency (CVID) 206 complimentary alternative medicine (CAM) 582 congenital ichthyosiform erythroderma 103 constitutional stigmata 70, 71 contact – allergy (CA) 58, 178, 429 – dermatitis 7, 101 – hypersensitivity 335 – urticaria 230 contamination 537 Coombs and Gell classification Coprinus comatus 446 Subject Index corneocyte 158, 182, 220, 524 corneodesmosome 220 corneotherapy 528 cornified cell envelope (CE) 247 corticophobia 598 corticosteroid 55, 272, 368, 477–479, 561, 571, 598 – unwanted effects 482 cortisol 477 cortisone 18, 548 Corynebacterium acnes 472 cosmetics 531 costimulatory molecule expression 291 costs 34 cow’s milk allergy 128, 154, 443 cradle cap 45, 228 Crohn’s disease 127 cross-contact 537 crusting 49 crystalline phase 220 cue-controlled relaxation 551 Cushing syndrome 483 cutaneous – barrier function 459 – biopsy 51 – catarrh 45 – lymphocyte-associated antigen (CLA) 323, 333, 343, 393 – lymphoma 129 – T-cell lymphoma 102 cyclic adenosine monophosphat (cAMP) 547 cyclones 511, 512 cyclopentanoperhydrophenanthrene 484 cyclosporin 33, 34, 318, 368, 368, 540, 602 cystic fibrosis (CF) 127 cytokine 185, 187, 307, 315, 318, 350, 351, 377 – gene cluster 257 – production 336 Dactylis glomerata 445 defensin 531 delayed-type hypersensitivity 186, 324, 350 dendritic cell (DC) 185, 265, 267, 288, 298, 335 – trafficking 344 Dennie-Morgan infraorbital fold (Morgan’s fold, Dennie’s fold) 65, 89 depression 545, 548 dermal – fibroblast 346 – fibrosis 352 derma-membrane structure (DMS) formulation 530 Dermatitis Family Impact Questionnaire (DFI) 33 dermatitis, see also atopic dermatitis, atopic eczema – herpetiformis Duhring (DHD) 101 – papulosa juvenilis (DPJ) 78 dermatofibrosarcoma 134 dermatogenic enteropathy 127 Dermatology Life Quality Index (DLQI) 33 dermatomyositis 102 Dermatophagoides pteronyssinnus 278, 392, 395, 396, 507 dermatophytic infection 116 dermatophytosis 101 dermocorticophobia 18 desensitization 17 desloratadine 504, 598 desquamation 158 dexamethasone 308 diabetes mellitus 144, 162 diacylglycerol (DAG)-dependent protein kinase C 336 diagnostic criteria 21, 48, 90 – according to Hanifin and Rajka 91 – according to Ring 91 – according to UK working party 90 diesel exhaust particulate (DEP) 386, 507 diet 535, 600 dietary allergen 16 DiGeorgi anomaly 104 digestive disturbance 46 dimethylsulfoxide (DMSO) 184, 373 dinitrochlorobenzene (DNCB) 178, 203 direct costs 34 dirty neck sign 77 disease gene discovery 256 disseminated wart 123 domestic allergen exposure 435 Dorfman-Chanarin syndrome 289 double-blind placebo-controlled food challenge (DBPCFC) 400, 536 Down’s syndrome 132 doxepin 226 Drosophila 419, 452 drug sensitivity 130 dry skin, see also xerosis 63, 83, 89, 157–163, 183, 219, 457, 524 – associated diseases 161 – irritants 160 – medication 163 – seasonal changes 160 – UV irradiation 160 Dubowitz syndrome 103, 132 dust mite allergen, see also house dust mite 391, 435 dyshidrosis 88 dyshidrotic eczema 43 earlobe rhagade 75 early colonization 453 Early Treatment of the Atopic Child (ETAC) study 153 East-West-German differences 23 E-cadherin 185, 328, 333 eczema, see also atopic eczema, atopic dermatitis – herpeticum 43, 53, 118, 119, 230, 497, 599 – infantum 40 – molluscatum 120, 121 – nails 86 – of the dorsum penis 76 – school academy 576 – vaccinatum 120, 230 – verrucatum 124 eczematous skin lesion 218 education programme 35, 552, 577 effector T cell 187 egg allergy 154 elicitation phase 186 elimination diet 535, 537, 600 elucidation 548 EMG biofeedback 550 emollients 525, 528 emotional – expression 568 – problems 31 emulsion bath oil 528 endometriosis 133 endothelial-leukocyte adhesion molecule-1 (ELAM-1) 307 endotoxin 27 – exposure 435 endurance training 517 Enterococcus faecalis 452 environmental – allergen 420, 433 – control 601 – pollution 376 – tobacco smoke (ETS) 385 envoplakin 366 enzyme – chymotrypsin-like 159 – trypsin-like 159 eosinophil 112, 299, 300, 305, 313, 317, 351, 392, 428, 560 – activation 317 – cationic protein (ECP) 112, 210, 313, 345, 382, 453, 539 – eosinophil-derived protein 340 – peroxidase (EPO) 110, 112 – recruitment 345 eosinophilia 391 eosinophilic – gastroenteritis 127 – inflammation 110 – protein X (EPX) 452 eotaxin 316, 325, 334 epicutaneous testing 417 607 608 Subject Index epidermal – barrier 444 – – dysfunction 191 – – function 487, 526, 529 – – homeostasis 182 – dendritic cell phenotyping (EDCP) 290 – differentiation complex (EDC) 247, 249 – growth factor receptor (EGFR) 334 – – activation 334 – – ligand 334 – hyperplasia 218, 415 – lipid 362 epidermis 352, 362, 368 epoxy resin 180 Eppendorf Itch Questionnaire 224, 225, 376 Epstein-Barr virus (EBV) 203 – antibodies 122 erythema 41, 77 erythromycin 493 Escherichia coli 205, 206 E-selectin 187, 282, 316, 323, 343 essential fatty acid 585 esterification 477, 478 European Task Force on Atopic Dermatitis (ETFAD) 444 evaporimeter 383 excoriation 40 exfoliating cheilitis 75 exfoliative erythroderma 43, 124 exocytosis 363 expressed sequence tag (EST) 340 extracellular matrix (ECM) 327 extracorporal photopheresis 600 extracutaneous viral disease 122 extrinsic – allergic bronchial asthma – atopic eczema 265 eyelid eczema 65, 68, 74, 88 ezrin-radixin-moesin family 248 facial pallor 67, 90 F-actin polymerization 278 familial eosinophilia 248 family environment 549 farnesol 493 Fas – expression 333 – ligand 327, 328 – receptor 56, 317 fatty – acid 364, 366, 585 – ointment 529, 530 FceRI (high-affinity IgE receptor) 188, 258, 279, 290, 298, 570 fexofenadine 504 fibrinogen 407 fibroblast 334 fibronectin 316, 407 – fibronectin-binding protein 406 fingerpad eczema 76 fingertip eczema 88 fish oil 586 flare-up 56, 574 flexural – dermatitis/eczema 38, 48, 228 – lesion 84 fluconazole 497 fluocortinbutyl 478 follicular eczema 229 food – allergen 58, 296, 300, 396, 442 – allergy 153, 399, 400, 402, 441, 534 – – testing 602 – challenge 536 – food-specific IgE 401 foot eczema 541 formaldehyde 381 frictional contact dermatitis 78 fungal aeroallergen 497 fur hat-like hairline 69 furry pet 26 fusidic acid 494, 599 gamma linolenic acid 54 gamma-globulin 119 gastric hyposecretion 127 gastrointestinal disorder 126, 127, 231 GATA-3 190 gene – disorder 248 – manipulation technology 410 – mapping 262 genetic – atopy risk 24 – etiology 235 – heterogeneity 256 – predisposition 426 genital wart 123 genome 238, 245, 260 genomic imprinting 241, 249, 255 Gentian violet 495 German Infant Nutrition and Intervention Study (GINI) 26 gingivostomatitis herpetica 118 glomerulonephritis 128 Glu420-Lys 240 glucocerebrosidase 161, 364 glucocorticoid 118, 126, 282, 318, 466, 474, 477, 540, 589 glucosaminoglycan (GAG) 306 glucosyl-ceramide 364 glycerol 460, 466, 530, 597 glycocalix 453 GM-CSF (granulocyte-macrophage colony stimulating factor) 332, 335, 336, 351 – mRNA 336 Gottron sign 102 G-protein-coupled receptor 325, 341, 343 graft-versus-host disease (GvHD) 101 grass pollen 74, 445 growth impairment 129 Haemophilus influenzae 205, 206 hairdresser 174 hairy leukoplakia 203 hand eczema 86, 88, 166–169, 456, 541 hapten 184, 186, 187, 333, 415 Hartnup’s disease 128 hay fever 4, 151, 152 head, neck and shoulder dermatitis (HNS dermatitis) 117, 230 health service planning 31 hearing loss 131 heat shock protein (HSP) 377 Hebra’s prurigo 12, 13 heliotherapy 515, 516 Helsinki Early Intervention Childhood Asthma (HEICA) 111 hematopoietic stem cell 277 hematopoietin 317 heparin 306 herbal treatment 586 Herpes simplex 43, 53, 101, 497, 573 Herthoge’s sign 68, 69, 90 HESTIBAR test procedure 545 high-affinity IgE receptor (FceRI) 188, 239, 258, 279, 290, 298, 317, 570 histamine 6, 222, 223, 270, 278, 304, 305, 352, 353, 384, 401, 417, 421, 519 histidine decarboxylase 353 histidinemia 129 histiocytosis X, see also Letterer-Siwe disease 102 Hodgkin’s disease 129 Hom s 420 homeopathy 587, 592 homiothermia 511 horny layer 457 hostility 545 house dust mite 26, 54, 296, 394, 428 – allergen 266 HPV type 16 122 human – biometeorological research 512 – immunodeficiency virus (HIV) 101, 122, 210 – – xerosis 162 – neutrophilic lipocalin (HNL) 112 Hurler’s syndrome 128 hydrocortisone 368, 477, 484, 551 – butyrate 293, 559, 571 – actate 571 hydrogel 465 hydrophilic emulsion 465 Subject Index hydrophobic cream 529 hydrotherapy 517 hydroxyzine 57 hygiene hypothesis 57, 189, 449, 452 Hymenoptera venom allergy 131, 231 hypericum extract 587 hyper-IgE syndrome 52, 95, 104, 207 hyper-IgM syndrome (HIGM) 132, 208, 258 hyperimmunoglobulinemia – E, see hyper-IgE syndrome – M, see hyper-IgM syndrome hyperkeratosis 77, 78, 218, 411 hyperlinearity – of the palms 63, 80 – of the soles 63, 89 hyperpigmentation 42 hyperplasia 411 hyperreflexia 133 hypersensitivity hypoallergenic diet 450 hypocorticism 483 hypoproteinemia 134 hyposensitization 152 hypothalamus-pituitary-adrenal cortical axis 547 hypothyroidism 69 ichthyosis 162 – linearis circumflexa Comel (ILC) 103 – vulgaris 49, 63, 64, 363 ichthyotic palm 219 idiosyncrasy 14 IFN – a 413 – g 144, 187, 189, 190, 265, 272, 297, 298, 326, 329, 333, 342, 557 IgE 96, 265, 326, 570 – antibodies 188, 214, 428 – autoreactivity 418, 419, 421 – hyperresponsiveness 332 – IgE-mediated allergy 38, 270, 296 – molecule 17 – regulation 6, 265, 269, 271, 413 – sensitization 296, 326 – testing 58 IgG autoantibody 421 IL 333, 350 – 377 – – q 297 – 187, 257, 265, 275 – – receptor 240, 270, 297 – – transgenic mice 415 illness-specific mental stress 551 immunodeficiency 103 – syndromes 132 immunoglobulin 270 – E, see IgE – G, see IgG immunoglobulin-deficiency syndrome 203 immunological – synapse 267 – tolerance 453 immunophenotyping 290 immunoreceptor tyrosine activation motif (ITAM) 304 impetiginization 42, 49, 53, 230 impetiginized eczema 42, 406 imprints 64 incidence rate 22 indirect costs 34 infantile atopic eczema 39, 45, 85 – diagnostic criteria 48 – differential diagnosis 50 infantile seborrhoeic dermatitis 18, 46 Infant’s Dermatitis Quality of Life Index (IDQoL) 33 infection 230, 436 – of the skin 482 inflammation 67 inflammatory – bowel disease 127 – dendritic epidermal cell (IDEC) 188, 276, 288, 290, 340, 344, 394, 570 infliximab 106 infraorbital fold 65, 89 inhalant 390, 396, 399 insect venom allergy 131 insulin promoter gene 144 insulin-dependent diabetes mellitus (IDMD) 144, 231 integrin 328 intellectualization 567 intercellular – adhesion molecule (ICAM) 333 – lipids 157, 159, 472 interferon, see IFN interferon-inducing factor (IGIF) 352 interleukin, see IL International Study of Asthma and Allergy in Childhood (ISAAC) 228 interview 22 intrinsic atopic eczema 265 involucrin 366 irritable skin 373 irritancy testing 374 irritant 429, 458, 601 – contact dermatitis (ICD) 168, 472 – exposure 172 isotype switching 270 itch 37, 40, 222, 228, 358, 375, 414, 427, 550, 580 – diathesis 13 – itch-scratch cycle 225 – mediators in inflamed skin 222 – rash 23 itraconazole 497 Janus kinase (JAK3) Job’s syndrome 207 juvenile – papular dermatosis – plantar dermatosis – – atopy-associated – – nonatopic variant 412 78 77, 78, 88 78 78 Kaposi-Juliusberg syndrome 53 Kaposi’s varicelliform eruption 117 keratinocyte 188, 189, 297, 332, 458, 472 – apoptosis 328 keratoconjunctivitis 125 keratoconus 125 keratohyaline granules 63 keratosis – follicularis 41, 90, 118, 219, 229 kerosene 383 ketotifen 110 Kitamura-Takahashi-Sasagawa syndrome 80 Klebsiella species 492 Lactobacillus 450 – acidophilus 452 – GG 450 – reuteri 452 – rhamnosus 450, 452 lactose intolerance 534 Langerhans cell 185, 275, 277, 288, 298, 323, 334, 335, 340, 344, 351, 393, 394, 428, 559 – histiocytosis 50 lanolin alcohol 181 laser Doppler imaging technique 374, 386 Lassar’s paste 18 latex 169 Leiner’s disease 103 LEKTI (lymphoepithelial Kazal-type related inhibitor) 209, 248, 307 Letterer-Siwe disease 102 leukotriene 417 Levocetirizine 504 lichen chronicus (VIDAL) 16 lichenification 14, 48, 218 lich´enification g´eante 125 lichenoid 86, 353 lid eczema 74 light sensitivity 375 linkage analysis 237 linoleic acid 367 lipid 362 – body 318 – peroxidation 160, 531 – solvents 375 lipocortin 479 609 610 Subject Index lipophilic – drug 466 – emulsion 463 lipopolysaccharide (LPS) 435 liposome 530 lipoteichoic acid (LTA) 407, 408 Lod score 237 log of the odds 237 long-chain saturated fatty acid (LCFA) 158 loratadine 505 loricrin 366 low hairline 69 L-selectin 187, 316 Lucifer yellow uptake 291 Lucky Luke diaper dermatitis 54 lung function 108 lupus erythematosus 345 lymphangiectasia of the small intestine 127 lymphocytes 41 – T regulatory 188 lymphohistiocytic infiltrate 288 lymphotactin 341 macrophage 277, 288, 560 – macrophage-derived chemokine (MDC) 325 macropinocytosis 266 macular amyloidosis 133 magnesium 161 major basic protein (MBP) 314, 345 major histocompatibility complex (MHC) 265 Malassezia 496 – furfur 42, 399 – sympodialis 81 manganese superoxide dismutase 418 maritime climate 514 massage therapy 587 mast cell 187, 238, 262, 279, 303, 308, 352, 381 – activation 304 – chymase 238, 257 – mediator 305 – protease 306 – tryptase 245 mastocytosis 303, 304 maternal atopic dermatitis 216 McGill Pain Questionnaire 224 measles infection 25, 123 Melaleuca alternifolia 493 melanocytic nervus 147 melanoma 147 memory T cell recruitment 342 Mendelian disorder 259 Mendel’s laws 256 menthol 226 metabolic disorder 128 metachromasia 303 meteorological complex entity 512 MHC 244, 272 microbial – colonization 191, 428 – infection 300, 428 microemulsion 525 milk protein hydrolysate 54 mineral 588 minor symptoms 37 mitochondria 358 MOAHL index 179 MOAHL-FA index 179 moisture accumulation test (MAT) 457 moisturizer 459, 466, 528 molecular genetics 426 molluscum contagiosum 120 – 122, 498 mometasone furoate (MMF) 478, 505 monocyte 189, 278, 300 – chemotactic protein 316 – monocyte-derived dendritic cell 278, 291 montelukast 113 mouse – asthma model 336 – chromosome 262 – model 325, 344 mucosal atopy 169, 459 mupirocin 485 muscle relaxation 550 music therapy 565 – active 566 – receptive 566 musical improvisation 566 m-xylene 384, 385 mycosis 117 – fungoides 102, 129, 323 mycotic infection 116 myeloid 278 myeloperoxidase 112 myositis-specific autoantibodies 102 natural moisturizing factor (NMF) 530 NC/Nga mice 411 necrosis 421 neomycin 181, 485, 494 nephropathy 592 nephrosis 123 nerve growth factor (NGF) 359, 414 Netherton’s syndrome 52, 102, 103, 132, 209, 248, 260, 289 – gene 239 neurasthenia 13 “Neurodermitis trainer” 578 neurokinin A 357 neuropeptide (NP) 357 – substance P 219, 357 – Y (NPY) 357 neurotrophin 359 neutral protease 306 NFkB 480 – activation 188 nickel 180, 181, 191 – patch test 459 niosome 530 nipple eczema 76, 89 nitrogen dioxide 382 nocturnal pruritus 53 nonatopic eczema 426 noninvolved skin of atopic dermatitis (NIAD) 161 nonionic alkylpolyglycoside 530 NOx exposure 27 nummular eczema 49, 86, 219 occupational – contact dermatitis (OCD) 168 – exposure 171 – guidelines 175 – skin disease 168, 172 – – attributable risks 173 octanol/water partition coefficient 181 octenidine 493 ocular disease 124, 231 Oid-Oid disease 289 oil emulsion 463 oil-in-water emulsion 464, 525 ointment – solution-type 484 – suspension-type 484 oleic acid vehicle 466 oligoantigenic diet 535 omalizumab 281 omega-hydroxy ceramides 158, 159, 161 oozing 11, 40, 41, 49 open air rest treatment 508, 516 oral – allergy syndrome (OAS) 536 – antihistamines 57 – provocation test 442, 536 orbital darkening 68, 90 OSSAD 32 osteomyelitis 116, 230 ovalbumin 346, 381, 387, 384 oxidative stress 377 ozone 387, 507, 587 palmar hyperlinearity 64 palmo-plantar keratoderma 131 papule 39, 84 papulovesicular lesion 86 PAR-2 222 paraffin gel 485 parakeratosis 218, 229, 411 parasitic disorders 123 parent-of-origin effect 255, 260 Parent’s Index of Quality of Life in Subject Index Atopic Dermatitis (PIQoL-AD) 33 passive smoking 601 patch testing 58, 97, 178 patchy pityriasiform lichenoid eczema 79, 80 paternal – atopic dermatitis 216, 241 – imprinting 241 pathogenetic factors 426 patient management program 549 peak exspiratory flow 108 pedagogic module 578 Pediatric Symptom Checklist 33 pemphigus foliaceus 101 penicillin 494 3-pentadecylcatechol (PDC) 178 peptidoglycan (PGN) 407 perennial rhinitis 68, 152 perioral eczema 75 periorbital darkening 90 (see allergic shiners) peripheral – blood 300, 315, 351 – nerve 357 periplakin 366 perl`eche 75, 89 peroxisome proliferator-activated receptor-a ligand 367 petrolatum 368 phenol 226 phenylalanine hydroxylase (PAH) 104 phenylketonuria 104, 128 phorbol ester 334, 335 phosphodiesterase (PDE) – inhibitors 557 – – antiinflammatory activity 559 – enzymes 557 phospholipase A 324 phospholipid 157 phosphorylation 412 photoprovocation testing 540 photosensitivity 130 phototherapy 496, 539 phytotherapy 528, 586 picryl chloride 415 pili torti 103 pimecrolimus 55, 57, 282, 292, 489, 496, 571, 572 pityriasis – alba 89 – rosea 134 Pityrosporum 203 (see Malassezia) – orbiculare 117, 446 – ovale 42, 204, 300 – species 291 plantar hyperlinearity 64 plasmocytoid dendritic cell 276–278 polar emulsion 463 polidocanol 181 pollen 387 – allergen 402 – allergy 536 – grains 266, 384 – pollen-sensitive atopic eczema 24 pollinosis 74, 79 pollutant 429 polyethylen glycol 529 – gel 465 polyhexadine 492 polyunsaturated fatty acid (PUFA) 585 pompholyx 43, 88 popliteal eczema 38 porrigo 11 positional cloning 235 positive predictive value (PPV) 401 positron emission tomography (PET) 223 poxvirus 121, 499 – officinalis vaccination 120 PPAR- * 185 p-phenylenediamine 180 precursor 10 prednisolone 477 prednisone 43 pre-employment screening 175 pregnancy 437 prevalence 22 prevention 54, 436 – primary 437 – secondary 438 Preventive Allergy Treatment (PAT) study 110 prick testing 58, 81, 96 primary immunodeficiency (PID) syndrome 202, 204, 210 primrose oil 585 probiotics 26, 54, 450, 451, 602 profibrotic cytokine 394 prognostic factors 27 prohapten 184 proinflammatory cytokine 381 Propionibacterium 472, 473 propylene glycol 466 prosaposin 365 prostaglandin E2 6, 267, 342, 386 protein – A 407 – nitrogen unit (PNU) 446 – oxidation 160 – synthesis 366 proteoglycan 306 Proteus species 492 provocation test 400, 441 prurigo 11, 87, 518 – Besnier’s 13 – diath´esique – ferox 12 – Hebra’s 12, 13 – nodularis 359 pruritic skin rash 391 pruritus 10, 50, 56, 89, 222, 225, 255, 399, 573 P-selectin 187, 316 – glycoprotein ligand 323 Psoralen and ultraviolet A (PUVA) therapy 126, 496, 599 – therapy 541, 600 psoriasin 247 psoriasis 10, 95, 130, 145, 162, 231, 239, 246, 297, 333–335, 345, 358 – susceptibility 238 psychoimmunology 546 psychological – disturbance 231 – training program 553 psychometric test 547 psychosomatic – factors 25 – illness 545 – influence 427 psychotherapeutic treatment 549, 568, 602 pulpite – digitale keratosique r´ecidivante 76 – s`eche 76, 167 pulpitis sicca 88 (see pulpite s`eche) pustule 39 pustulosis vacciniformis acuta 117 pyridoxine 588 quality of life (QOL) 32, 544 questionnaire 22, 23 – on Experience with Skin Complaints (QES) 32 radiation 587 radioallergosorbent test (RAST) 96, 395, 418, 535 – reaction 241 RANTES 240, 245, 259, 316, 325, 336 rash 358 rebound phenomenon 486 reflex erythema 90 respiratory – allergy 417 – syncytial virus 449 retroauricular intertrigo 75 rhagades 77 rheumatoid arthritis 146, 231 rhinitis 4, 391 Rhus toxicodendron 178 roxithromycin 493 salt – bath 588 – water 517 Sarcoptes scabiei 101 scabies 10, 50, 95, 101 Schwann cell 358 611 612 Subject Index SCORAD 32, 55, 91, 225, 229, 407, 442, 451, 504, 576 – classification – – of edema/papulation 93 – – of erythema 93 – – of excoriation 94 – – of lichenification 95 – – of oozing/crusting 94 – evaluation form 92 – tool 224 scratching 414, 427, 551 sebaceous gland lipid 159 seborrhoeic dermatitis 46, 49, 95, 100, 101, 204, 358 sebostasis 63 sedation 503 selective IgA deficiency 95, 206, 208 Self-Administered Eczema Area and Severity Index (SA-EASI) 32 self-esteem 579 self-respect 579 semisolid emulsion 464 senile xerosis 163 sensitization 184 – experiment 178 sensory – fiber 357 – nerve system 223 serine protease 239, 257 Serratia marcescens 471 serum – cortisol 518 – IgE level 96, 104 – immunoglobulin 410 severe combined immunodeficiency (SCID) 104 S´ezary syndrome 102, 124, 129, 323 SF-36 34 shaking lotion 465 Shwachman syndrome 209 Sickness Impact Profile (SIP) 34 silent atopy 71 single nucleotide polymorphism (SNP) 239, 297 skin – aging 163 – barrier function 220, 275, 413, 427, 456 – care 597 – cleansing 468, 526 – colonization 406 – disease – – chronic inflammatory 100 – – impact 31 – eosinophilia 346 – hydration 457, 466 – hyperirritability 378 – infection 203 – inflammation 558 – – – – – lesion 84 lipid 458 milk 529 permeability barrier function 368 prick test 96, 215, 244, 296, 442, 445, 534 – protocol 580 – skin-selective homing ligand 324 – surface conductance (SSC) 413 – pH 471, 473, 526 – tumor 203 sleep disturbance 130 smallpox 53, 120 – vaccination 498 soap 468, 471, 526 social environment 565 socioeconomic status (SES) 25 sodium – dodecyl sulfate (SDS) 373, 473 – lauryl sulfate (SLS) 160, 373, 473, 527 sorption-desorption test 457 soybean oil 585 specific – IgE – – antibodies 96 – – level 401 – immunotherapy (SIT) 272 – serum IgE 442 sphingomyelin 362, 364 – deacylase 161 sphingomyelinase 366 sphingosine 498 SPINK5 248, 249, 260, 307 spondylosis 133 spongiosis 80, 229, 328, 559 – of the follicular epithelium 79, 81 spreading bath oil 528 stage-adapted treatment 597 staphylococcal – colonization 571 – enterotoxin B (SEB) 324 – infection 116 – peptidoglycan 408 – scalded skin syndrome (SSSS) 116 Staphylococcus – albus 472 – aureus 40, 53, 101, 118, 190, 203, 230, 249, 300, 353, 399, 406, 471, 472, 485, 492, 560, 571 – – coagulase-positive 115 – – infection 207 START (Steroid Treatment As Regular Therapy in early asthma) study 111 stasis dermatitis 181 STAT6 190 status eczematicus 378 stem cell factor 303 steroid 110, 111, 495 – steroid-responsive nephrotic syndrome (SRNS) 128 stigmata of atopic eczema 4, 62, 375, 377 stigmatization 32, 567 stratum corneum 157, 161, 182, 362, 364, 524 – hydration 158 – lipids 367 – proteins 159 streptococcal impetigo 116 Streptomyces tsukubaensis 570 streptozotocin (STZ) 181 stress 544, 546, 580 – coping technique 551 strophulus 11 subacute eczematous lesion 85 sudden infant death syndrome (SIDS) 132 sulfur dioxide 383 superinfection 53 supplementation diet 600 surface lipid 367, 376 surfactant 426, 469, 527 sweating 375 switch recombinase system 270 syndet 469, 471, 474, 536, 597 synthetic detergent/surfactant 469 systemic immunity 353 T cell 298, 428, 570 – activation 267, 271 – allergen-specific clones 275 – chemotaxis 325 – lymphoma 102, 129 – polarization 268 – receptor (TCR) 267 – response 342 – skin-selective homing 323 – subset 186 – suppression 202 T helper cell 265, 278, 342 – polarization 268 T lymphocytes 333, 393 T regulatory (Tr) lymphocytes 188 T regulatory cell (Treg) 190 T2-mediated delayed-type hypersensitivity reaction 281 tachyphylaxis 487 tacrolimus 33, 34, 55, 57, 282, 292, 293, 318, 368, 489, 496, 570–572, 602 tar preparation 18, 486 tea tree oil (TTO) 493 (see Melalenca) terbutaline 111 terfenadine 497 tetra-chloroethylene 385 textiles 375 TGF- q 240 Th1 – dichotomy 25 Subject Index – Th1-mediated disease 144, 147 Th2 – dichotomy 25 – phenotype 144 – Th2-mediated disease 144 thalassotherapy 511, 514, 516 theory of Brocq 14 therapeutic – discussion 566 – project 55 thermoregulation 520 thick liquid emulsion 464 thymic – hypoplasia 104 – stromal lymphopoietin (TSLP) 189, 275, 335 thymidine incorporation assay 291 thymus and activation-regulated chemokine 325 tinea corporis 89 tissue – damage 421 – eosinophilia 313, 315 – microenvironment 345 tixocortol pivalate 484 TNF- [ 185, 297, 307, 315, 333, 344, 350, 377 tobacco smoke 27, 385 tolerance 453 toll-like receptor (TLR) 277, 352, 408, 452 toluene 385 topical – antibiotics 56 – corticosteroids 8, 56, 226, 282, 482, 486, 487 – immunomodulator 292, 496 – inhibitors of calcineurin 489 (see tacrolimus, pimecrolimus) – preparation 181 – treatment 55 – vehicles 463 total serum IgE level 244 training program 576 transepidermal water loss (TEWL) 158, 183, 219, 374, 382, 384, 456, 520, 524 transforming growth factor beta (TGF- q ) 453 transmission disequilibrium testing (TDT) 238, 256 trichophytin 117 Trichophyton rubrum 117 trichorrhexis – invaginata 103, 260 – nodosa 103 triclosan 492 trisomy 21 132 truncal – dermatitis 38 – lesion 85 trypsin-like enzyme 159 tubular dressing 56 tumor necrosis factor a, see TNF- [ twin study 255 Tzanck smear test 119, 497 UK Working Party’s Diagnostic for Atopy Dermatitis Criteria 90 (see diagnostic criteria) ulcerative colitis 127 ultraviolet radiation 516 (see UV) unconventional therapy option (UTO) 603 urea 460, 466, 474, 530, 597 uremia 162 urticaria 12, 41, 58, 308 – pigmentosa 304 utility question 34 UV – A/B phototherapy 588 – A1 phototherapy 539 – B radiation 541 – irradiation 130, 573, 599 – light 368 vaccination 25, 498 vaccinia virus 498 vacular endothelium 344 varicella zoster virus infection 122 vasoactive – intestinal peptide (VIP) 357 – mediator 427 vasoconstriction – of small blood vessels 67 – test 478 vasocortin 479 vasomotor rhinitis venom allergy 131 (see Hymenoptera) vernal keratoconjunctivitis 125 vesicles 41, 84 – on erythematous skin 84 vesicular virus infection 498 viral – infection 118, 202, 276 – skin affection 497 – wart 123 visual analog scale (VAS) 224 vitamine 588 – B2 588 – E 530, 588 vitiligo 89, 131 Vohwinkel’s syndrome 247 volatile organic compounds (VOC) 376, 384 von Recklingshausen’s disease 241 Waardenburg-Klein syndrome 131 wart 123 water-free emulsion 463 water-in-oil emulsion 464 weather reaction 511 wheat allergy 402 white dermatographism 66, 70, 90 Wiskott-Aldrich – protein (WASP) 205 – syndrome (WAS) 95, 103, 202, 204, 240, 259 – – eczema 205 work-related exogenous factor 166 World Allergy Organization (WAO) wrist eczema 85 xenobiotics 181, 182, 184 xerosis, see also dry skin 39, 41, 49, 63, 89, 160, 350, 524, 526, 528 X-linked – agammaglobulinemia (Bruton) 207 – hypohidrotic ectodermal dysplasia 51 – ichthyosis (RXI) 162 Yamamoto’s sign 38, 41 Zemaphyte 586 613 ... 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... 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... 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