Adverse Cutaneous Drug Eruptions

Transcription

1 Chemical Immunology and Allergy 97 Adverse Cutaneous Drug Eruptions Bearbeitet von L.E. French, H. Renz 1. Auflage Buch. XIV, 240 S. Hardcover ISBN Gewicht: 790 g Weitere Fachgebiete > Medizin > Klinische und Innere Medizin > Immunologie schnell und portofrei erhältlich bei Die Online-Fachbuchhandlung beck-shop.de ist spezialisiert auf Fachbücher, insbesondere Recht, Steuern und Wirtschaft. Im Sortiment finden Sie alle Medien (Bücher, Zeitschriften, CDs, ebooks, etc.) aller Verlage. Ergänzt wird das Programm durch Services wie Neuerscheinungsdienst oder Zusammenstellungen von Büchern zu Sonderpreisen. Der Shop führt mehr als 8 Millionen Produkte.

2 Section Title XIII Preface French, L.E. (Zurich) 1 Epidemiology of Cutaneous Adverse Drug Reactions Mockenhaupt, M. (Freiburg) 1 Abstract 1 Essentials in a Nutshell 2 Introduction 2 Clinical Pattern of Cutaneous Adverse Drug Reactions 2 Non-Life-Threatening Cutaneous Adverse Drug Reactions 3 Life-Threatening Cutaneous ADR 3 Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis 3 Acute Generalized Exanthematous Pustulosis 4 Drug Reaction with Eosinophilia and Systemic Symptoms 4 Epidemiologic Studies on Cutaneous Adverse Drug Reactions 5 Epidemiologic Studies on Severe Cutaneous Adverse Reaction 6 Incidence and Demographic Data 6 Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis 7 Acute Generalized Exanthematous Pustulosis 7 Drug Reaction with Eosinophilia and Systemic Symptoms 8 Etiology of Cutaneous Adverse Drug Reactions 8 Etiology and Medication Risk of Severe Cutaneous Adverse Reaction 8 Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis 13 Acute Generalized Exanthematous Pustulosis 14 Drug Reaction with Eosinophilia and Systemic Symptoms 15 Genetic Epidemiology on Cutaneous Adverse Drug Reactions 15 References 18 Genetics and the Potential for Predictive Tests in Adverse Drug Reactions Pirmohamed, M. (Liverpool) 18 Abstract 19 Essentials in a Nutshell 19 Introduction 20 Investigation into the Genetics of Cutaneous Drug Eruption 23 Genetic Predisposing Factors for Cutaneous Adverse Drug Reactions 23 Abacavir Hypersensitivity and HLA- B* Carbamazepine- Induced Hypersensitivity Reactions 26 Allopurinol- Induced Serious Cutaneous Adverse Drug Reactions 27 Predisposition to Drug- Induced Blistering Disease 27 Conclusions and Future Perspectives V

3 28 Acknowledgements 28 References 32 Etiology and Pathogenesis of Adverse Drug Reactions Hausmann, O.; Schnyder, B.; Pichler, W.J. (Bern) 32 Abstract 32 Essentials in a Nutshell 33 Introduction 34 Pathogenesis 34 Type A Reactions 35 Type B Reactions 35 Defective or Absent Enzymes 35 Nonspecific Cytokine Dysbalance 36 Nonspecific Dysbalance of Inflammatory Mediators 36 Nonspecific Mast Cell Degranulation 37 Specific Immune Reactions (True Allergies) 37 Sensitization 37 IgE- Mediated Allergic Reactions 38 IgG- Mediated Cytotoxicity (Type II) 38 Immune Complex Deposition (Type III) 38 T Cell- Mediated, Delayed Drug Hypersensitivity Reactions (Type IV) 40 Contact Dermatitis 40 Delayed- Type Hypersensitivity Reactions in the Skin after Systemic Drug Administration 42 Cross- Reactivity 42 Flare- Up Reactions 43 Genetic Factors 43 Conclusion 44 References 47 Diagnostic Approach to Drug Allergy Harr, T. (Zurich) 47 Abstract 47 Essentials in a Nutshell 47 Introduction 49 Diagnostic Approach for Selected Types of Adverse Cutaneous Drug Reactions 49 Stevens- Johnson Syndrome/Toxic Epidermal Necrolysis (Lyell Syndrome) 50 Acute Generalized Exanthematous Pustulosis 50 Fixed Drug Eruption 51 Diagnostic Approach in Hypersensitivity Reactions to Selected Substances 51 Excipients and Stabilizers 52 Iodine- Containing Preparations 53 Antineoplastic Drugs 54 Neuromuscular Blocking Agents 54 Betalactams 56 Biologicals 57 References 61 Histopathological Patterns Indicative of Distinct Adverse Drug Reactions Kerl, K. (Zurich) 61 Abstract 61 Essentials in a Nutshell 62 Drug Reactions with Superficial and Deep Dermal Infiltrates 62 Maculopapular Drug Reaction 62 Urticarial Drug Reaction 62 Lymphomatoid (Pseudolymphomatous) Drug Reaction VI

4 63 Drug Reaction with Eosinophilia and Systemic Symptoms 63 Photoallergic Reactions 63 Drug- Induced Lupus Erythematosus 64 Drug Reactions with Predominant Cytotoxic Epidermal Changes 64 Erythema Multiforme/Fixed Drug Eruption 65 Stevens- Johnson/Toxic Epidermal Necrolysis 65 Phototoxic Reactions 66 Chemotherapy- Induced Cytotoxic Reactions: Epidermal Dysmaturation and Acral Erythema 66 Radiation Recall Dermatitis 66 Lichenoid Pattern Lichen Planus- Like Reactions 68 Spongiotic Pattern 68 Pityriasis rosea- Like Drug Eruption 68 Baboon Syndrome 69 Granulomatous Pattern 69 Interstitial Granulomatous Drug Eruption 69 Vasculitic Pattern 69 Hypersensitivity vasculitis 74 Psoriasiform Pattern 74 Psoriasis Induced by Drugs 74 Acute Generalized Exanthematous Pustulosis 75 Neutrophilic Drug Reactions 75 Neutrophilic Eccrine Hidradenitis 75 Halogenodermas 75 Vesiculobullous Drug Reactions 75 Linear IgA Dermatosis- Like Drug Reaction 76 Drug- Induced Pemphigus 76 Drug- Induced Bullous Pemphigoid 76 Drug- Induced Pseudoporphyria Cutanea Tarda 76 Panniculitis Induced by Drugs 77 Folliculitis 77 Acneiform Drug Eruptions 77 Drug- Induced Eosinophilic Pustular Dermatosis 77 Sclerodermoid Drug Reactions 78 References 79 Uncomplicated Drug-Induced Disseminated Exanthemas Bircher, A.J. (Basel) 79 Abstract 79 Essentials in a Nutshell 80 Introduction 81 Morphology 84 Localization, Distribution, and Evolution 84 Chronology 86 Etiology 88 Pathophysiology 91 Special Manifestations of Benign or Uncomplicated Drug Exanthemas 91 Symmetrical Drug- Related Intertriginous and Flexural Exanthema 91 Pityriasiform Exanthemas 92 Psoriasiform Exanthemas 92 Erythroderma 93 Lichenoid and Pseudolymphomatous Forms 93 Interstitial Granulomatous Drug Reaction 93 Erythema Nodosum 93 Acute Febrile Neutrophilic Dermatosis (Sweet s Syndrome) 94 Differential Diagnosis 95 Diagnostic Procedures VII

5 95 Therapeutic Options 96 References 98 Drug-Induced Angioedema Lerch, M. (Winterthur) 98 Abstract 98 Essentials in a Nutshell 98 Introduction 99 Types of Angioedema 100 Drug- Induced Angioedema 102 Diagnostics and Treatment 103 Conclusions 104 References 106 Fixed Drug Eruption: The Dark Side of Activation of Intraepidermal CD8+ T Cells Uniquely Specialized to Mediate Protective Immunity Shiohara, T.; Mizukawa, Y. (Tokyo) 106 Abstract 106 Essentials in a Nutshell 107 Introduction 108 Clinical Manifestations of Fixed Drug Eruption 110 Unusual Forms of Fixed Drug Eruption 113 Histology of Fixed Drug Eruption 114 Diagnosis of Fixed Drug Eruption 116 Clinically Relevant Issues of Disease Pathogenesis 118 Conclusion 119 Acknowledgement 119 References 122 Drug-Induced Hypersensitivity Syndrome: Recent Advances in the Diagnosis, Pathogenesis and Management Shiohara, T.; Kano, Y.; Takahashi, R.; Ishida, T.; Mizukawa, Y. (Tokyo) 122 Abstract 122 Essentials in a Nutshell 123 Introduction 124 Epidemiology 124 Clinical Findings 126 Overlap with Other Severe Drug Eruptions 127 Laboratory Findings 129 Diagnosis of Drug- Induced Hypersensitivity Syndrome 131 Pathology 131 Pathogenesis 133 Complications and Long- Term Sequelae 134 Management of Drug- Induced Hypersensitivity Syndrome 135 Conclusion 136 Acknowledgement 136 References 139 Acute Generalized Exanthematous Pustulosis Sidoroff, A. (Innsbruck) 139 Abstract 139 Essentials in a Nutshell 140 Introduction 140 Epidemiology 140 Clinical Features VIII

6 142 Histopathology 142 Differential Diagnoses 142 Generalized Acute Pustular Psoriasis (von Zumbusch Type) 143 Stevens- Johnson Syndrome and Toxic Epidermal Necrolysis 143 Drug Hypersensitivity Syndrome 143 Subcorneal Pustular Dermatosis (Sneddon- Wilkinson) 143 Pustular Vasculitis 144 Candidiasis 144 Others 144 Etiology and Pathogenesis 146 Treatment 147 References 149 Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Harr, T.; French, L.E. (Zurich) 149 Abstract 149 Essentials in a Nutshell 150 Introduction 150 Epidemiology 151 Clinical Features 151 Acute Phase 153 Late Phase and Sequelae 154 Etiology and Pathogenesis 154 Genetic Susceptibility 154 Pathomechanism of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis 155 Drugs 156 Diagnosis and Diagnostic Methods 156 Differential Diagnosis 156 Management and Therapy 156 Treatment in Acute Stage 157 Evaluation of Severity and Prognosis 157 Rapid Withdrawal of Culprit Drug(s) 157 Best Supportive Care 158 Specific Therapy 160 Treatment of Sequelae 160 Allergological Testing 161 Prognosis 161 References 167 Phototoxic and Photoallergic Cutaneous Drug Reactions Glatz, M.; Hofbauer, G.F.L. (Zurich) 167 Abstract 167 Essentials in a Nutshell 167 Introduction 168 Incidence of Drug- Induced Phototoxic and Photoallergic Reactions 171 Drug- Induced Phototoxic Cutaneous Reactions 171 Pathophysiology 171 Clinical Manifestations of Phototoxicity 171 Acute Phototoxicity 172 Chronic Phototoxicity 172 Hyperpigmentation of Phototoxic Skin Reactions 173 Pseudoporphyria 173 Photoonycholysis 173 Lichenoid Phototoxic Reactions 173 Telangiectatic Phototoxic Reactions 173 Histopathology of Phototoxic Skin Reactions 174 Drug- Induced Photoallergic Cutaneous Reactions IX

7 174 Pathophysiology 175 Clinical Manifestations of Photoallergy 175 Chronic Actinic Dermatitis 176 Lichen Planus- Like Photoallergic Skin Reactions 176 Histopathology of Photoallergic Skin Reactions 176 Evaluation of Patients with Phototoxicity and Photoallergy 177 Differential Diagnoses of Phototoxicity and Photoallergy 178 Management of Patients with Phototoxicity and Photoallergy 179 References 180 Immediate and Delayed Cutaneous Reactions to Radiocontrast Media Brockow, K. (Munich) 180 Abstract 180 Essentials in a Nutshell 181 Epidemiology of Hypersensitivity Reactions to Radiocontrast Media 181 Classification of Radiographic Contrast Media Hypersensitivity Reactions 182 Clinical Presentations of Immediate and Non- Immediate Hypersensitivity 184 Pathophysiology 184 Immediate Radiocontrast Media Hypersensitivity 185 Pathophysiology of Non- Immediate Reactions 186 Role of Iodine in Contrast Media Hypersensitivity 186 Diagnosis 187 Skin Tests 187 Laboratory Tests 188 Provocation Tests 189 Prevention 190 References 191 Cutaneous Drug Eruptions Associated with the Use of New Oncological Drugs Belloni, B.; Schönewolf, N.; Rozati, S.; Goldinger, S.M.; Dummer, R. (Zurich) 191 Abstract 191 Essentials in a Nutshell 192 Introduction 192 Epidermal Growth Factor Receptor Inhibitors 194 Multikinase Inhibitors 198 BRAF Inhibitors 199 MEK Inhibitors 200 Acute Changes 200 Chronic Changes 201 References 203 Cutaneous Drug Eruptions Associated with the Use of Biologics and Cutaneous Drug Eruptions Mimicking Specific Skin Diseases Seneschal, J.; Milpied, B.; Taieb, A. (Bordeaux) 203 Abstract 203 Essentials in a Nutshell 203 Introduction 204 Psoriasiform Eruptions 207 Lichenoid Eruptions 208 Vasculitis 209 Lupus Erythematous- Like Eruptions 210 Vesiculobullous Drug Eruptions 210 Drug- Induced Pemphigus 210 Drug- Induced Bullous Pemphigoid 211 Drug- Induced Pseudoporphyrias 211 Drug- Induced Linear IgA Bullous Eruption X

8 212 Acneiform Eruptions 213 Drug- Induced Interstitial Granulomatous Dermatitis 213 Lymphomatoid Drug Eruptions 214 Skin Pigmentation Disorders 214 Drug- Induced Hypopigmentation 214 Hair Disorders 214 Drug- Induced Hair Loss 215 Drug- Induced Hirsutism or Hypertrichosis 215 Drug- Induced Changes in Hair Structure 215 Conclusion 216 References 217 Desensitization for Hypersensitivity Reactions to Medications del Carmen Sancho, M.; Breslow, R.; Sloane, D.; Castells, M. (Boston, Mass.) 217 Abstract 218 Essentials in a Nutshell 218 Introduction 218 General Principles and Proposed Mechanisms of Rapid Drug Desensitization 220 Clinical Rapid Desensitization: Protocols and Agents 222 Rapid Drug Desensitization to Antibiotics 225 Rapid Drug Desensitization to Chemotherapeutic Agents: Taxanes 225 Rapid Drug Desensitization to Chemotherapeutic Agents: Platins 227 Rapid Drug Desensitization to Monoclonal Antibodies 228 Overall Safety and Efficacy 229 Treatment of Reactions during Desensitization 230 Conclusions 231 References 234 Author Index 235 Subject Index XI

9 Section Title Preface As a result of improved treatment outcomes, longer patient survival, extended treatment courses, and polymedication of an ageing population, patients are exposed to drugs more frequently and for longer time periods, increasing the risk of sensitization to medications. As a consequence, the frequency of adverse drug reactions is regularly increasing. The skin is one of the most frequently involved organs in adverse drug reactions. Cutaneous adverse reactions to drugs are observed in 0.1 1% of patients during premarketing clinical trials, and postmarketing analyses suggest that their incidence can be as high as 1 8% for certain types of drugs (NSAIDS, antibiotics, antiepileptics), and among hospitalized patients the incidence of these reactions ranges from 1 to 3%. The majority of adverse cutaneous drug eruptions are benign in nature, comprised largely by the maculopapular type of drug eruption and urticaria. Nonetheless, studies suggest that roughly a third of drug eruptions require hospital management and are considered as severe, although fortunately only 2% of cutaneous drug eruptions are really life- threatening. As a consequence, it is estimated that between 5 and 9% of all hospital costs are related to adverse drug eruptions, and cutaneous adverse drug eruptions representing 20 30% of all drug eruptions the burden of these on the health care system is considerable. Although the pathomechanism of the benign and severe forms of cutaneous drug eruptions remains incompletely understood, great progress in this field of medicine has been made in the past few years. Improvements range from the clinical classification that is essential for a better understanding to the identification of genetic susceptibilities to certain drugs, and consequently the development of the first preventive genetic screening measures for selected patient groups and drug classes. In this book, a selected group of experts have provided an up- to- date, condensed and clinically relevant overview of the field of cutaneous drug eruptions ranging from the epidemiological basics and novel knowledge of genetic predisposition to the available therapeutic measures including rapid drug desensitization. XIII

10 We hope to provide physicians, be it generalists or specialists, and non- physicians (nurses and scientists) with a useful tool for a better diagnosis, understanding and management of cutaneous drug eruptions in daily practice. Lars E. French, Zurich XIV French