Chemical Immunology and Allergy
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1 Anaphylaxis
2 Chemical Immunology and Allergy Vol. 95 Series Editors Johannes Ring Munich Kurt Blaser Davos Monique Capron Lille Judah A. Denburg Hamilton Stephen T. Holgate Southampton Gianni Marone Naples Hirohisa Saito Tokyo
3 Anaphylaxis Volume Editor Johannes Ring Munich 32 figures, 1 in color, and 37 tables, 2010 Basel Freiburg Paris London New York Bangalore Bangkok Shanghai Singapore Tokyo Sydney
4 Chemical Immunology and Allergy Formerly published as Progress in Allergy (Founded 1939), continued as Chemical Immunology Edited by Paul Kallós , Byron H. Waksman Prof. Dr. med. Dr. phil. Johannes Ring Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein Technische Universität München Christine Kühne Center for Allergy Research and Education (CK-CARE) Biedersteiner Strasse 29 DE München (Germany) Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents and PubMed/MEDLINE. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2010 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISSN ISBN e-isbn
5 Section Title Contents XI Preface Ring, J. (Munich) XII Charles M. Richet on Anaphylaxis. A Facsimile (1904) History and Epidemiology 1 History and Classification of Anaphylaxis Ring, J.; Behrendt, H.; de Weck, A. (Munich/Pamplona) 1 Abstract 2 History 4 Pathophysiology of Anaphylaxis 6 Clinical Symptomatology 9 Management of Anaphylaxis 9 Allergens and Elicitors 10 References 12 Epidemiology of Anaphylaxis Worm, M. (Berlin) 12 Abstract 12 Sources of Information on the Epidemiology of Anaphylaxis 13 Limitations 13 Causes of Anaphylaxis 13 Food 15 Drugs 16 Insect Venom Anaphylaxis 17 Biphasic Anaphylactic Reaction 17 Age 18 Atopy 18 Geography 18 Gender 19 Socioeconomic Status 19 References Mechanisms 22 T-Cell Response to Allergens Ozdemir, C. (Istanbul); Akdis, M.; Akdis, C.A. (Davos) V
6 22 Abstract 23 Allergen Recognition by the Immune System 23 Pathogen-Associated Molecular Patterns and Pattern Recognition Receptors 26 Dendritic Cell Subsets 26 Dendritic Cell/T-Cell Interaction 28 T-Cell Activation Signals 29 Effector T-Cell Subsets 29 Th1 and Th2 Cells 30 T-Helper-17 Cells 31 T-Helper-9 Cells 31 Regulatory T Cells 34 T Cells in Allergen-Specific Immunotherapy 34 Treg Cells in Suppression of Effector Cells 35 T-Cell/B-Cell Interaction, IgE Production 36 IL-10 and Treg Cells in Suppression of IgE 36 T Cells in Late-Phase Reactions 37 Conclusion 37 Acknowledgements 37 References 45 Anaphylaxis: Mechanisms of Mast Cell Activation Kalesnikoff, J.; Galli, S.J. (Stanford, Calif.) 45 Abstract 46 Use of Mouse Models to Study Anaphylaxis 49 IgE-Dependent Anaphylaxis: FcεRI Signaling 50 Proximal Signaling Events 52 Calcium Regulation 53 Membrane Fusion Events 54 Negative Regulation of FcεRI-Dependent Mast Cell Activation 57 Factors Modulating (or Tuning ) FcεRI-Dependent Mast Cell Functional Activation 57 Effects of IgE on Surface Levels of FcεRI, Survival and Mediator Production 58 Variation in the Mast Cell s Responsiveness to Activation 59 Endogenous Products that Modulate Responses to Aggregation of FcεRI 61 Other Immune and Non-Immune Mechanisms of Anaphylaxis 62 Concluding Remarks 63 References 67 Kinins, Airway Obstruction, and Anaphylaxis Kaplan, A.P. (Charleston, S.C.) 67 Abstract 68 Introduction 69 Proteins 70 Mechanisms of Bradykinin Formation (Contact Activation) 72 Cell Surface Assembly of the Plasma Kinin-Forming Cascade 73 Kinin Formation at the Surface of Endothelial Cells 73 Angioedema 74 C1 Inhibitor Deficiency 74 Causes and Inheritance 75 Molecular Genetics 76 Diagnosis 76 Pathogenesis 77 Acquired C1 Inhibitor Deficiency 78 Treatment 79 Other Hereditary and Non-Hereditary Angioedemas 79 Kinins and Anaphylactic-Like Reactions 80 References VI Contents
7 85 Role for Basophils in Systemic Anaphylaxis Karasuyama, H. (Tokyo); Tsujimura, Y. (Tokyo/Tsukuba-shi); Obata, K.; Mukai, K. (Tokyo) 85 Abstract 85 Biology of Basophils 87 Newly Identified Roles for Basophils 87 Basophils Drive Th2-Cell Differentiation through Secretion of Th2 Cytokines and Antigen Presentation 88 Basophils Enhance Humoral Memory Response 88 Basophils Initiate IgE-Mediated Chronic Allergic Inflammation 89 A Crucial Role for Basophils in Anaphylaxis 90 Systemic Anaphylaxis in the Absence of Mast Cells and IgE 91 A Crucial Role for Basophils in IgG-Mediated Systemic Anaphylaxis 93 Basophils Release Platelet-Activating Factor Instead of Histamine to Induce IgG-Mediated Systemic Anaphylaxis 94 Possible Roles for Human Basophils in Anaphylaxis 95 Perspective 95 References 98 Human Cardiac Mast Cells in Anaphylaxis Genovese, A.; Rossi, F.W.; Spadaro, G.; Galdiero, M.R.; Marone, G. (Naples) 98 Abstract 99 Human Heart Mast Cells 99 Preformed Mediators Synthesized by HHMC 101 Lipid Mediators de novo Synthesized by HHMC 101 Cytokines Synthesized by HHMC 102 Immunologic and Non-Immunologic Stimuli that Activate HHMC in vitro 103 Role of HHMC in Systemic and Cardiac Anaphylaxis 103 Cardiovascular Effects of Histamine Infusion in Man 104 Effects of Activation of the H 1 Receptor on Coronary Hemodynamics in Man 105 Hemodynamic Effects of Cysteinyl Leukotrienes in Man 105 Conclusions 106 Acknowledgements 107 References Diagnosis and Clinical Symptomatology 110 Mastocytosis Brockow, K. (Munich); Metcalfe, D.D. (Bethesda, Md.) 110 Abstract 111 Description 111 Pathogenesis 112 Clinical Features 112 Cutaneous Involvement 113 WHO Classification of Systemic Involvement 115 Mast Cell Mediator-Induced Symptoms 116 Mastocytosis and Anaphylaxis 116 Frequency of Anaphylaxis in Patients with Mastocytosis 116 Clinical Features of Anaphylaxis 117 Elicitors of Anaphylaxis 118 Diagnosis 119 Therapy 120 Avoidance of Trigger Factors and Treatment of Anaphylaxis 121 Therapy of Mast Cell Mediator-Induced Symptoms 121 Therapy of Skin Lesions 122 Therapy of Aggressive Forms of Mastocytosis 122 Acknowledgement 123 References Contents VII
8 125 In vitro Diagnosis of Anaphylaxis Sanz, M.L. (Pamplona); Gamboa, P.M. (Bilbao); García-Figueroa, B.E.; Ferrer, M. (Pamplona) 125 Abstract 126 Diagnosis of Anaphylactic Reaction 126 Mediators in Anaphylaxis 126 Histamine 126 Tryptase 127 Chymase 128 Mast Cell Carboxypeptidase A3 128 Platelet-Activation Factor 128 Diagnostic Tools for the Identification of Anaphylaxis-Triggering Allergens 129 Drugs 129 β-lactam Antibiotics 129 Neuromuscular Blocking Agents (NMBA) 131 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 132 Other Drugs 133 Latex 133 Anisakis Allergy 133 Insect Venom Allergy 134 Foods 136 Diagnosis by Components. Microarrays to Determine Specific IgE 137 Acknowledgements 137 References Allergens and Elicitors 141 Insect Venoms Müller, U.R. (Bern) 141 Abstract 141 Taxonomy and Biology of Responsible Insects 142 Apidae 143 Vespidae 144 Ants (Formicidae, Myrmicidae) 145 Allergens in Hymenoptera Venoms 146 Allergens in Apid Venoms 146 Allergens in Vespid Venoms 147 Allergens in Ant Venoms 147 Recombinant Venom Allergens 148 Clinical Presentation of Anaphylaxis to Hymenoptera Venoms 148 Epidemiologic Aspects 149 Diagnosis 149 History 150 Skin Tests and Specific IgE Antibodies 151 Other Tests 151 Prevention and Emergency Treatment 151 Immunotherapy 151 Efficacy and Safety 153 Indications 154 Immunotherapy Protocols and Duration 154 References 157 Classification and Pathophysiology of Radiocontrast Media Hypersensitivity Brockow, K.; Ring, J. (Munich) 157 Abstract 158 Classification of Adverse Reactions to Radiographic Contrast Media VIII Contents
9 159 Clinical Presentation of Radiocontrast Media Hypersensitivity 160 Pathophysiology of Immediate Reactions 163 Pathophysiology of Non-Immediate Reactions 165 Diagnosis 165 Immediate Hypersensitivity Reactions 166 Non-Immediate Hypersensitivity Reactions 167 Prevention 168 Acknowledgements 168 References 170 Analgesics Szczeklik, A. (Cracow) 170 Abstract 170 Historical Note 173 Classification 173 Aspirin-Induced Asthma 175 Prevention and Treatment 176 Aspirin-Sensitive Urticaria/Angioedema 176 Hypersensitivity to Pyrazolones 177 Allergic Anaphylactic Reactions to NSAIDs 178 Acknowledgements 178 References 180 Anaphylaxis to General Anesthetics Moneret-Vautrin, D.A.; Mertes, P.M. (Nancy) 180 Abstract 181 Epidemiology 181 Specific Clinical Features of Anesthesia Induced Anaphylaxis 183 Population at Risk 183 Causal Agents 184 NMBAs: Immune-Mediated Hypersensitivity Reactions Are Predominant 185 Non-Immune-Mediated Hypersensitivity Reactions 186 Investigation of an Allergic Reaction 187 Histamine and Tryptase during Peroperative Anaphylaxis 187 Skin Testing 188 Conclusion 188 References 190 Anaphylactic Reactions to Local Anesthetics Ring, J.; Franz, R.; Brockow, K. (Munich) 190 Abstract 191 Chemical Structure 192 Clinical Symptomatology 193 Toxicity 193 Pharmacologic Effect 193 Hypersensitivity Reactions 193 IgE-Mediated Anaphylaxis 193 Contact Allergy (Type IV Reactions) 194 Non-Immune Anaphylactic ( Pseudo-Allergic ) Reactions 194 Results of Skin Test and Provocation Test Procedures 195 Psychosomatic Involvement 196 Reverse Placebo Provocation 197 Diagnostic Work-Up 197 Conclusion 198 Acknowledgement 199 References Contents IX
10 Treatment and Prevention 201 Anaphylaxis: Acute Treatment and Management Ring, J.; Grosber, M. (Munich/Davos); Möhrenschlager, M. (Davos); Brockow, K. (Munich) 201 Abstract 202 Basic General Treatment Modalities 203 Epinephrine (Adrenaline) 204 Glucocorticosteroids 205 Antihistamines 205 H 1 -Antagonists 205 H 2 -Antagonists 205 Volume Replacement 206 Additional Drugs 206 General Management of Patients Having Undergone an Anaphylactic Reaction 207 References 211 Epinephrine (Adrenaline) in Anaphylaxis Simons, F.E.R.; Simons, K.J. (Winnipeg, Man.) 211 Abstract 212 Pharmacologic Activity 213 Therapeutic Window 213 Epinephrine: Evidence Base for Use in Anaphylaxis 214 Epinephrine Dosing 214 Rationale for Intramuscular Injection 215 Rationale for Intravenous Injection 215 Epinephrine Autoinjector Use in First-Aid Treatment 215 Dilemmas in Dosing 216 How Many Epinephrine Doses Are Needed? 217 Stability of Epinephrine Solution 217 Alternative Routes of Epinephrine Administration for First-Aid Treatment 217 Reason for Failure to Inject Epinephrine Promptly 218 Reasons for Occasional Lack of Response to Epinephrine 218 Context of Epinephrine Use as First-Aid Treatment 218 Anaphylaxis Emergency Action Plan 219 Medical Identification 219 Anaphylaxis Education 219 Future Directions 220 References 223 Author Index 224 Subject Index X Contents
11 Section Title Preface Among several emergencies in allergy, anaphylaxis is probably the most dramatic and life-threatening reaction giving rise to a considerable number of fatalities, some of which often go unrecognized. It is important to stress this life-threatening character of an allergic reaction in a time when allergic diseases are regarded by some as minor complaints or just impairment of feeling well. The dangerous character of this type of allergy is based not only upon the dramatic clinical symptomatology when it occurs, but also on the fact that affected individuals once having survived an episode are seemingly healthy and tend to neglect the risk of a future episode. Furthermore, there is the problem of hidden allergens which makes it almost impossible for a person suffering from food anaphylaxis for example to avoid the allergen in daily life since declaration rules are leaky but also inadvertent or false contaminations may occur or even transfer of allergen from another individual to the patient for example by a kiss! As spectacular as these events are sometimes referred to in the yellow press, as negligent many doctors and also scientists as well as patients are behaving in spite of this potentially life-threatening risk. I would like to tell a very personal episode: When I came back from my post-doctoral fellowship at Scripps Clinical Research Foundation in La Jolla to the Munich Dermatology Department in 1978, I started the allergen-specific immunotherapy with purified insect venom extracts which had just been so successfully tried in the historic double-blind, placebo-controlled trial by the group of Lawrence Lichtenstein in Baltimore. Since then, I have treated several thousand patients successfully and given many lectures on the topic, sometimes ad meam nauseam I felt I can no longer listen to myself telling the same story. In spite of this, in my rather close circle of acquaintances, one day a 35-year-old young man who was aware of the problem he had with insect stings with minor flush episodes or itching palms, but had not taken this seriously, died when he was mountain climbing in the Karwendel mountains in Bavaria. This shock motivated me to continue to preach like the voice in the wilderness. It just shows you that it is important to bring the message and the scientific progress to the people. This was also the main motivation to put together this book, because for some time since the last Novartis Foundation Symposium volume 2004 not so much has been comprehensively compiled on this topic. I am very grateful to the excellent group of authors who have contributed to this book, to Dr. Franz and Dr. Grosber, as well as to Mr. Nold, Ms. Smit and Mr. Jappert from Karger Publishers who were of tremendous help in the editing process. May this book be widely distributed not only among allergists but among all doctors dealing with patients potentially affected in order to prevent anaphylactic reactions, but also in order to correctly treat these patients both in the acute phase as well as in the long-term management. Johannes Ring XI
12 Charles M. Richet on Anaphylaxis A Facsimile (1904) Richet CM: De l anaphylaxie ou sensibilité croissante des organismes à des doses successives de poison. Arch Fisiol 1904;1: Despite intensive research neither the editor nor the publisher could locate the copyright holder of this article. The publisher would be pleased to hear from anyone whose rights unwittingly have been infringed. All legal claims as customary and appropriate will be compensated upon receipt of relevant notification. XII
13 XIII
14 XIV Richet
15 Facsimile: Article on Anaphylaxis by Charles M. Richet (1904) XV
16 XVI Richet
17 Facsimile: Article on Anaphylaxis by Charles M. Richet (1904) XVII
18 XVIII Richet
19 Facsimile: Article on Anaphylaxis by Charles M. Richet (1904) XIX
20 XX Richet
21 Facsimile: Article on Anaphylaxis by Charles M. Richet (1904) XXI
22 XXII Richet
23 Facsimile: Article on Anaphylaxis by Charles M. Richet (1904) XXIII
24 XXIV Richet
25 Facsimile: Article on Anaphylaxis by Charles M. Richet (1904) XXV
26 XXVI Richet
contact activation in formation diseases 67 endothelial cells and kinin formation 73 processing and degradation 68 70
Subject Index Adenosine, mast cell activation modulation 60 Age, risk factor 17, 18 Allergen elicitors 9, 10 insects, see Insect venom-induced microarrays for 136 overview of characteristics 23 recognition
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