B.M. Czarnetzki . Urticaria

Beate M. Czarnetzki

Urticaria

With 40 Color and 21 Black-and-White Figures

Springer-Verlag Berlin Heidelberg New York Tokyo

Professor B.M. Czarnetzki, M.D. Department of Dermatology School of Medicine University of Miinster Von-Esmarch-Str. 56 D-4400 Miinster

ISBN-\3: 978-3-642-70315-7 e-ISBN-\3: 978-3-642-703\3-3 001: 10.1007/978-3-642-703\3-3

Library of Congress Cataloging in Publication Data Czarnetzki, Beate M.: Urticaria I B. M. Czarnetzki. -Berlin; Heidelberg; New York; Tokyo: Springer, 1986.

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, reuse of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under §54 of the German Copyright Law, where copies are made for other than private use, a fee is payable to Verwertungsgesellschaft Wort, Munich. © by Springer-Verlag Berlin Heidelberg 1986 Softcover reprint of the hardcover 15t edition 1986 Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. The use of 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. Typesetting, printing and binding: K. Triltsch, Wiirzburg 2329/3321-543210

Table of Contents

Preface

1 1.1 1.2 1.3 1.4 1.5 1.6 1.7

2 2.1 2.2 2.2.1 2.2.2 2.2.3 2.2.4 2.2.5 2.2.6 2.3 2.3.1 2.3.2 2.3.3 2.3.4

2.3.5 2.3.6 2.3.7 2.3.8 2.3.9 2.3.10 2.4

3 3.1 3.2 3.3 3.3.1 3.3.2 3.3.3 3.3.4 3.3.5 3.4 3.4.1 3.4.2

History of Urticaria . .............. . Introduction ..................... . Nomenclature .................... . Pathogenetic Theories ............. . The Physical Urticarias ........... . Urticaria Pigmentosa ............. . Angio(neurotic)edema ............. . Treatment ....................... .

Basic Mechanisms ................ . The Wheal ...................... . The Mast Cell ................... . Morphological Aspects ............ . Mast Cell Heterogeneity ........... . Mast Cell Receptors .............. . Mast Cell Triggering .............. . Modulation of Mast Cell Release ... . Mast Cell Granules ............... . Mediators ....................... . Histamine ....................... . 5-Hydroxytryptamine (Serotonin) ... . Kinins .......................... . Slow-Reacting Substances (Leukotrienes C4 , D 4 , E4 ) •••.••••••

Platelet Activating Factor ......... . Prostaglandins ................... . Complement ..................... . Chemotactic Factors .............. . Heparin ......................... . Enzymes and Enzyme Inhibitors .... . Overview of Pathogenetic Aspects .. .

Acute and Chronic Urticaria . ....... . Definition ....................... . Classification .................... . Epidemiology .................... . Incidence ........................ . Age ............................ . Sex ............................. . Types of Urticaria ................ . Atopy .......................... . Clinical Aspects .................. . Cutaneous Lesions ................ . Noncutaneous Symptomatology .... .

1 1

3 3 3 4

5 5 6 7 7 7 9

11 12 13 13 16 16

17 17 18 19 21 22 23 24

26 26 26 27 27 27 27 27 27 28 28 29

3.4.3 3.4.4

Anaphylaxis . . . . . . . . . . . . . . . . . . . . . . 30 Serum Sickness. . . . . . . . . . . . . . . . . . . . 30

3.4.5 Course and Prognosis ............. . 3.5 Histopathology .................. . 3.6 Laboratory Findings .............. . 3.6.1 Leukocytes ...................... . 3.6.2 Immunoglobulins ................. . 3.6.3 Complement and Protease

Inhibitors ....................... . 3.7 Specific Causes of Reactions ....... . 3.7.1 General Aspect of Drug Reactions .. . 3.7.2 Penicillin ........................ . 3.7.3 Sulfonamides and Antibiotics Other

3.7.4 3.7.5 3.7.6 3.7.7 3.7.8 3.7.9 3.7.10

Than Penicillin ................... . Various Other Drugs ............. . Implants ........................ . Vaccines ........................ . Blood Products and Substitutes .... . Seminal Plasma .................. . Contrast Media .................. . Food ........................... .

3.7.11 Infections ....................... . 3.7.12 Inhalants ........................ . 3.7.13 Hormones and Endocrine Disorders 3.7.14 Internal Disease .................. . 3.7.15 Neurological and Psychic Factors ... . 3.8 Diagnosis and Differential Diagnosis. 3.8.1 General Considerations ........... . 3.8.2 Specific Diseases ................. .

4 Angioedema . ..................... . 4.1 General Aspects and Epidemiology .. 4.2 Classification .................... . 4.3 Clinical Aspects .................. . 4.3.1 Cutaneous Symptoms ............. . 4.3.2 Extracutaneous Symptoms ......... . 4.4 Associated Diseases ............... . 4.5 Course and Prognosis ............. . 4.6 Histology and Ultrastructure ....... . 4.7 Pathogenesis ..................... . 4.7.1 Biochemical Defects in Hereditary

Angioedema ..................... . 4.7.2 Pathogenesis of Acquired

Angioedema ..................... . 4.8 Laboratory Findings .............. . 4.9 Genetics ........................ .

31 31 31 31 32

32 32 32 33

34 35 35 35 35 35 35 36 38 40 41 42 43 43 43 45

47 47 47 48 48 49 50 50 50 51

51

52 52 53

VI

4.10 4.11

5 5.1 5.2 5.3 5.3.1 5.3.2 5.3.3 5.4

5.4.1 5.4.2 5.4.3

5.4.4 5.4.5

5.4.6

5.4.7 5.4.8 5.4.9 5.4.10 5.5 5.6 5.6.1 5.6.2 5.6.3 5.6.4 5.6.5 5.6.6 5.6.7 5.7 5.7.1 5.7.2 5.7.3 5.7.4 5.7.5 5.7.6 5.7.7 5.7.8 5.7.9 5.7.10 5.8 5.8.1 5.8.2 5.8.3 5.8.4 5.8.5 5.8.6 5.8.7

Diagnosis ....................... . Differential Diagnosis ............. .

The Physical Urticarias . ........... . General Aspects .................. . Epidemiology and Clinical Aspects .. . Pathogenesis ..................... . Passive Transfer .................. . Mediators ....................... . Unifying Pathogenetic Scheme ..... . Dermographic Urticaria (Urticaria Factitia) ............... . Clinical Aspects and Epidemiology .. . Cutaneous Symptoms ............. . Systemic Manifestations and Laboratory Findings .............. . Morphological Changes ........... . Special Types of Dermographic Urticaria ........................ . Other Diseases Associated with Dermographic Urticaria ........... . Diagnosis ...................... " Differential Diagnosis ............. . Prognosis ......... '" ........... . Pathogenesis ..................... . Vibratory Angioedema ............ . Pressure Urticaria ................ . Epidemiology .................... . Clinical Features ................. . Laboratory Findings .............. . Associated Diseases ............... . Histological Findings ............. . Diagnosis ....................... . Pathomechanisms ................. . Cold Urticaria ................... . General Aspects .................. . Clinical Features ................. . Histological Findings ............. . Laboratory Findings .............. . Associated Diseases ............... . Diagnosis ....................... . Differential Diagnosis ............. . Prognosis ....................... . Pathogenesis ..................... . Special Types of Cold Urticaria .... . Cholinergic Urticaria ............. . Epidemiology .................... . Local Symptoms ................. . Systemic Symptoms ............... . Laboratory Findings .............. . Histology ....................... . Associated Diseases ............... . Diagnosis .................... , .. .

53 54

55 55 55 57 57 57 58

58 58 59

59 59

60

62 62 62 63 63 64 64 64 65 66 66 66 67 67 68 68 69 70 71 71 71 72 73 73 74 75 75 75 75 76 76 76 77

Table of Contents

5.8.8 5.8.9 5.8.10

Differential Diagnosis ............. . Pathogenesis ..................... . Variant Types of Cholinergic Urticaria and Related Diseases ..... .

5.9 Solar Urticaria ................... . 5.9.1 General Aspects and Epidemiology .. 5.9.2 Cutaneous Reactions .............. . 5.9.3 Systemic Symptoms ............... . 5.9.4 Laboratory Findings .............. . 5.9.5 Histology ....................... . 5.9.6 Underlying and Associated Diseases 5.9.7 Diagnosis ....................... . 5.9.8 Differential Diagnosis ............. . 5.9.9 Prognosis ....................... . 5.9.10 Pathogenesis ..................... . 5.10 Heat Contact Urticaria ............ . 5.10.1 General Aspects .................. . 5.10.2 Local Reactions .................. . 5.10.3 Systemic Symptoms ............... . 5.10.4 Laboratory Findings .............. . 5.10.5 Associated Diseases ............... . 5.10.6 Histological Findings ............. . 5.10.7 Diagnosis ....................... . 5.10.8 Differential Diagnosis ............. . 5.10.9 Prognosis ....................... . 5.10.10 Pathogenesis ..................... . 5.11 Aquagenic Urticaria .............. . 5.11.1 General Aspects .................. . 5.11.2 Clinical Findings ................. . 5.11.3 Diagnosis and Differential Diagnosis. 5.11.4 Pathogenesis ..................... .

6 Contact Urticaria . ................ . 6.1 General Aspects and Classification .. . 6.2 Clinical Manifestations ............ . 6.2.1 Local Appearance, Time Course,

and Histology .................... . 6.2.2 Systemic Symptoms ............... . 6.3 Immunologically Mediated Contact

Urticaria ............ " ..... '" .. . 6.4 Contact Urticaria due to

Histamine Liberators ............. . 6.5 Venom-Induced Contact Urticaria .. . 6.6 Contact Urticaria due to Unknown

Mechanisms ..................... . 6.7 Pathomechanisms of Contact

Urticaria ... " ..... , ............. . 6.7.1 Mechanism of Release ............ . 6.7.2 Mediators Involved in Contact

Urticaria ........................ . 6.7.3 Local Factors Important for

Development of Contact Urticaria .. . 6.8 Diagnosis of Contact Urticaria ..... . 6.8.1 Clinical Diagnosis ................ .

77 77

79 79 79 80 80 81 81 81 82 82 82 83 83 83 84 84 84 85 85 85 85 85 85 87 87 87 87 87

89 89 89

89 90

90

91 91

93

93 93

94

94 94 94

Table of Contents

6.8.2 Diagnostic Skin Tests. . . . . . . . . . . . .. 95 6.8.3 Further Diagnostic Tests . . . . . . . . . . . 95

7 Anaphylactoid Reactions. . . . . . . . . . .. 96 7.1 Definition . . . . . . . . . . . . . . . . . . . . . . .. 96 7.2 Classification. . . . . . . . . . . . . . . . . . . .. 96 7.3 Epidemiological Aspects. . . . . . . . . . .. 97 7.4 Agents Eliciting Anaphylactoid

7.4.1 7.4.2 7.4.3 7.4.4 7.4.5 7.5 7.5.1 7.5.2 7.5.3 7.5.4 7.6 7.6.1 7.6.2 7.6.3

7.6.4 7.6.5

7.7 7.7.1

7.7.2 7.7.3

7.7.4 7.8

7.8.1 7.8.2 7.8.3

8 8.1 8.2 8.3 8.3.1 8.3.2 8.4 8.5 8.6 8.6.1 8.6.2 8.6.3 8.6.4

Reactions ........................ 98 Analgesics. . . . . . . . . . . . . . . . . . . . . . . . 98 Preservatives and Colorings. . . . . . . .. 98 Radiocontrast Media. . . . . . . . . . . . . . . 99 Plasma Expanders. . . . . . . . . . . . . . . .. 99 Anesthetics . . . . . . . . . . . . . . . . . . . . . .. 100 Clinical Features. . . . . . . . . . . . . . . . .. 100 Symptomatology .................. 100 Kinetics of the Reaction. . . . . . . . . . .. 100 Laboratory Findings ............... 100 Prognosis ........................ 101 Diagnosis ........................ 101 Patient History ................... 101 Skin Tests ........................ 101 Sequential Tests for Vascular Response. . . . . . . . . . . . . . . . . . . . . . . .. 102 Oral Provocation Tests ...... , ...... 102 In Vitro Tests for Lymphocyte Transformation ................... 104 Pathogenesis ...................... 104 Immunoglobulins, Mast Cells, Mast Cell Mediators. . . . . . . . . . . . . .. 105 Arachidonate Metabolism .......... 105 Involvement of the Complement Pathway ......................... 106 Other Theories. . . . . . . . . . . . . . . . . . .. 106 Pathogenetic Aspects of Intoletance Reactions to Special Reagents. . . . . .. 107 Contrast Media . . . . . . . . . . . . . . . . . .. 107 Volume Expanders ................ 107 Drugs for Anesthesia .............. 108

Urticarial Vasculitis Syndrome ...... 109 General Aspects. . . . . . . . . . . . . . . . . .. 109 Epidemiology ..................... 109 Clinical Aspects . . . . . . . . . . . . . . . . . .. 109 Cutaneous Manifestations . . . . . . . . .. 109 Systemic Manifestations. . . . . . . . . . .. 110 Histopathology ................... 110 Immunopathology ................. 112 Laboratory Findings ............... 112 Erythrocyte Sedimentation Rate ..... 112 Immunoglobulins. . . . . . . . . . . . . . . . .. 112 Complement System ............... 112 Immune Complexes. . . . . . . . . . . . . . .. 112

VII

8.7 Diagnosis ........................ 112 8.8 Differential Diagnosis. . . . . . . . . . . . .. 113 8.9 Prognosis ........................ 114 8.10 Pathogenesis ...................... 114 8.10.1 Immune Complexes ................ 114 8.10.2 Mediators ........................ 114 8.10.3 Relationship to the Arthus Reaction 115 8.10.4 Other Pathogenic Factors .......... 115

9 Mastocytosis (Urticaria Pigmentosa) .. 116 9.1 Introduction ...................... 116 9.2 Cutaneous Mastocytosis. . . . . . . . . . .. 116 9.3 Systemic Mastocytosis ............. 117 9.4 Symptomatology .................. 117 9.5 Histology. . . . . . . . . . . . . . . . . . . . . . .. 117 9.6 Laboratory Findings ............... 119 9.7 Diagnosis ........................ 120 9.8 Pathogenesis. . . . . . . . . . . . . . . . . . . . .. 121 9.9 Prognosis ........................ 121

10 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . .. 122 10.1 Introduction ..................... , 122 10.2 History .......................... 122 10.2.1 Clinical Appearance and Symptoms .. 122 10.2.2 Potentially Provoking or

Associated Factors ................ 122 10.2.3 Physical Examination .............. 124 10.3 Laboratory Procedures ............. 124 10.3.1 Screening Tests .................... 124 10.3.2 Specific Diagnostic Laboratory

Tests ............................ 125 10.3.3 Laboratory Tests for Diagnosis of

10.3.4 10.3.5 10.3.6 10.4 10.4.1

IgE-Dependent Allergy (RAST and RIST) ................. 125 In Vivo Provocation Tests. . . . . . . . .. 127 Tests for Physical Urticarias . . . . . . .. 130 Oral Challenge Tests ............... 131 Diagnosis by Avoidance. . . . . . . . . . .. 131 Social Habits and Environmental Factors .......................... 131

10.4.2 Drugs ............................ 131 10.4.3 Diet ............................. 131 10.5 Diagnosis by Therapy .............. 133

11 Therapy. . . . . . . . . . . . . . . . . . . . . . . . .. 134 11.1 Basic Therapeutic Considerations. . .. 134 11.2 Specific Therapeutic Modalities. . . . .. 135 11.2.1 Antihistamines.................... 135 11.2.2 Beta-Adrenergic Agonists . . . . . . . . . .. 138 11.2.3 Corticosteroids .................... 138 11.2.4 Inhibitors of Mast Cell Secretion . . .. 139 11.2.5 Kallikrein Inhibitors . . . . . . . . . . . . . .. 140 11.2.6 Mast Cell Mediator Depletion .... " 140 11.2.7 Miscellaneous Therapeutic Agents ... 140

VIII

11.2.8 Hyposensitization ................. 141 11.3 Treatment of Acute and Chronic

11.3.1 11.3.2 11.3.3 11.4 11.4.1 11.4.2 11.4.3

Urticaria ........................ , 142 Acute Urticaria ................... 142 Anaphylaxis ..................... , 143 Chronic Urticaria ................. 144 The Physical Urticarias ............ 144 Dermographic Urticaria. . . . . . . . . . .. 144 Cholinergic Urticaria .............. 145 Cold Urticaria ................... , 145

11.4.4 Solar Urticaria .................... 146 11.4.5 Heat Contact Urticaria. . . . . . . . . . . .. 147 11.4.6 Pressure Urticaria. . . . . . . . . . . . . . . .. 148

Table of Contents

11.5 Mastocytosis. . . . . . . . . . . . . . . . . . . . .. 148 11.6 Urticarial Vasculitis Syndrome ...... 149 11.7 Hereditary Angioedema ........ " .. 149 11.7.1 Danazol. ......................... 149 11.7.2 Plasmin Inhibitors ................. 151 11.7.3 Replacement Therapy with Fresh

Frozen Plasma and ClINH ........ 151 11. 7 .4 Practical Clinical Guidelines .. . . . . .. 151

References .............................. 153

Index ................................... 179

Abbreviations

Ab antibody HHT hydroxyheptadecatrienoic acid ACTH adrenocorticotrophic hormone HMW high molecular weight ADCC antibody dependent cellular cytotoxicity HPETE hydroperoxyeicosatetraenoic acid Ag antigen 5-HT 5-hydroxytryptamine AGE PC acetyl glyceryl ether phosphorylcholine HU heat urticaria ANA antinuclear antibody Aqu. U. aquagenic urticaria IC immune complex ATP adenosine triphosphate IFA inflammatory factor of anaphylaxis

Ig immunoglobulin BHA butylated hydroxyanisole BHT butyrylhydroxytoluol kd kilodalton BK bradykinin BSP bromosulfophthalein LIF leukocyte migration inhibiting factor

LIM lymphocyte/macrophage C complement LO lipoxygenase Ca calcium LPS lipopolysaccharide cAMP cyclic adenosine 3',5'-phosphoric acid LT leukotriene CG cysteinyl-glycinase lys enzyme lysosomal enzyme cGMP cyclic guanosine 3',5'-phosphoric acid chol u cholinergic urticaria MC mast cell chr u chronic urticaria MIF migration inhibiting factor CNS central nervous system MLC mixed lymphocyte culture co cyclooxygenase min minute(s) Con A concanavalin A CT connective tissue neg negative CU cold urticaria NK natural killer (assay)

NSAID nonsteroidal antiinflammatory drugs d dalton NT neurotransmitter DMSO dimethyl sulfoxide DS dextran sulfate OPT oral provocation test DSCG disodiumcromoglycate DU dermographic urticaria P properdin

PAF platelet activating factor EACH a complex of erythrocytes, antibodies PG prostaglandin

against erythrocytes and C 1 S PLA2 phospholipase A2 EACA epsilon-aminocaproic acid pos positive ECF(A) eosinophil chemotactic factor (of ana- PTA plasma thrombin activator

phylaxis) PU pressure urticaria ESR erythrocyte sedimentation rate PUPPP pruritic urticarial papules and plaques of

pregnancy GGTP y-glutamyl transpeptidase PUVA psoralen-UVA combination therapy GI gastrointestinal

RA rheumatoid arthritis factor h hour RAST radioallergosorbens test HETE hydroxyeicosatetraenoic acid RBC red blood cells HF Hageman-factor RIST radioimmunosorbens test

X Abreviations

s second SLE systemic lupus erythematosus SRS slow reacting substance(s) ST skin test

1J{ thromboxane UV ultraviolet light zy zymosan

Preface

Urticaria is a vexing problem, to the patient who suffers from the annoying pruritus and the fear oflife­threatening reactions, to the physician who faces the challenge to find the cause of the eruption and to control the symptomatology, and to the scientist who is asked to explain the process that elicits tissue swelling at the cellular and molecular levels.

The last thorough treatise on urticaria was the superb monograph by R. P. Warin and R.H. Champion, published more than a decade ago. Since then, there have been major advances in the field. This holds particularly for the clinical aspects of anaphylactoid reactions, the urticarial vasculitis syndrome, and the understanding of the pathogenesis of all major types of urticaria. Progress has become possible through new insights into the biology of mast cells and basophils and through the study of mediators of acute allergic reactions of which one type, the leukotrienes, have only very recently been discovered.

This book is meant to provide an in-depth review of all major basic and clinical aspects of urticaria. It is intended to serve as a reference for clinicians who are confronted with diagnostic and therapeutic problems and as a source of information for scientists about the state of our current understanding of the pathogenesis of urticaria. Hopefully on this basis, researchers can progress in their endeavor to unravel the many unknown factors in the pathogenesis' of the broad spectrum of diseases with urticarial reactions.

Seneca once said that a long way is made short and efficient through guidance and example. The list of

teachers who have stimulated my interest and helped me to understand the basic and clinical aspects of mast cell-related problems is long. I would like to specifi­cally mention J.N. Fink during medical school train­ing in Milwaukee, J.R. Pomeranz and R.W. Belcher during dermatology residency in Cleveland, L.M. Lichtenstein and P. Norman during a research fellow­ship at the Department of Clinical Immunology and Allergy at Johns Hopkins University in Baltimore, and E. Macher at the University Clinics in Miinster where much of what I have learned in the past could be broadened through further basic research and clinical experience.

My thanks go also to all the following friends and colleagues who have critically reviewed parts of this book: P.J. Frosch, Heidelberg; G. Goerz, Dusseldorf; H. Kastner, J. Knop and E. Macher, Munster; E. Kownatzki, Freiburg; M. Loos, Mainz; H. Merck, Cologne; W. Opferkuch, Bochum; J. Ring, Munich; H. Schadewaldt, Dusseldorf; W. Sterry, Kiel; G. Stingl, Vienna; V. Voigtlander, Mannheim; R.P. Warin, Bristol; H.H. Wolff, Lubeck.

The book could never have been finished without the untiring, enthusiastic help of Ms M. v. Lovenberg and Ms K. Staigis who did the typing even during their free time, and of Ms J. Buckmann and Mr. P. Wissel who did the photographic work. Finally, a word of appreciation should go to those closest to me who patiently and generously shared with me many trying months of reading and writing. Munster, February 1985