According to most studies, allergic reactions represent 35%-50% of all untoward reactions to drugs, yet the pharmacological literature concerning the clinical aspects, diagnosis, and pathophysiological mechanisms of drug allergy is markedly less extensive than reports dealing with the toxicological or pharmacological effects of drugs. The main reasons for this state of affairs may be on the one hand that until a few years ago the pathophysiological mechanisms of the various types of allergic reactions were not well understood, and on the other hand that objective diagnosis of a drug allergy is still fraught with serious difficulties. Drug allergy is still an unpopular topic for most allergologists and pharmacologists; this is reflected by the fact that despite their frequency, allergic reactions to drugs still occupy a relatively small proportion of space in most pharmacology handbooks and in classical books devoted to the side effects of drugs. There has recently been considerable progress in research into the immunologi­ cal and pathophysiological events occurring in allergic reactions, and on that basis investigations of various drug allergies have also yield~d new objective findings. Consequently, it was natural to attempt a review of the most frequent and important drug allergies in the form of a handbook. We originally intended to present a comprehensive review of all drug allergies, but the realization of this goal soon became more difficult than we had at first imagined.

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Section I: General Aspects of Drug Allergies.- 1 Immunochemical Basis of Allergic Reactions to Drugs.- A. Introduction.- I. Definitions.- II. Miscellaneous Parameters in Sensitization.- 1. Chemical Characteristics of the Antigen.- 2. Antigen Metabolism.- 3. Genetic Aspects.- B. Cellular and Immunochemical Elements in Antigenicity.- I. Cellular Aspects.- II. Antigenic Determinants Reacting with Antibody.- III. Antigenic Determinants in Cellular Reactions.- C. Antigenicity and Drugs.- I. Agents of Intrinsic Immunogenicity.- II. Low Molecular Weight Drugs as Immunogens.- 1. The Formation of Antigenic Determinants.- 2. The Formation of Complete Immunogens.- III. Immunogenic Complexes not Involving Covalent Linkage Between Hapten and Carrier.- IV. Molecular Parameters in Elicitation and Inhibition of Allergic Reactions.- References.- 2 Chemical and Pharmaceutical Aspects of Drug Allergy.- With 23 Figures.- A. Introduction: Routes of Formation of Drug Antigens.- B. Immunologically Active Macromolecular Contaminants of Penicillins.- C. Polymerization of ?-Lactam Antibiotics.- I. Penicillin Polymers.- 1. Formation and Structure of Polymers.- 2. Immunologic Effects of Polymers.- 3. Prevention of Penicillin Polymerization.- II. Cephalosporin Polymers.- D. Reactions Between Penicillins and Pharmaceutical Adjuvants.- E. Chemically Reactive Impurities and Degradation Products.- I. Acetylsalicylic Acid.- II. Phenindione.- III. Phenylbutazone.- IV. Corticosteroids.- V. Penicillins.- References.- 3 Immunopathological Mechanisms and Clinical Aspects of Allergic Reactions to Drugs.- With 4 Figures.- A. Introduction.- B. Chemical Properties Involved in the Allergenic Potential of Drugs.- I. Formation of Immunogenic Conjugates.- II. Reactive Derivatives and Metabolites.- III. Requirements for Allergens Eliciting Antibody-Mediated Reactions.- IV. Requirements for Allergens Eliciting Cell-Mediated (Delayed-Type) Allergic Reactions.- V. Impurities and Galenic Factors Involved in Sensitization.- C. Induction of Immune Responses to Drugs: Main Factors Involved.- I. Factors Involving the Sensitizing Drug.- 1. Chemical Structure and Reactivity.- 2. Cross-Sensitization.- 3. Dose, Duration, and Number of Courses of Therapy.- 4. Mode of Administration.- II. Factors Involving the Patient.- 1. The Immune System and the Regulation of Immune Responses to Drugs.- 2. Age and Sex.- 3. Genetic Factors.- 4. Underlying Diseases.- 5. Variable Relationship Between the Immune Response to a Drug and the Incidence of Clinical Allergic Symptoms.- D. Immunopathological Mechanisms of Allergic Reactions to Drugs.- I. Antibody-Mediated Reactions.- 1. Anaphylactic Reactions.- 2. Cytotoxic Reactions.- 3. Immune Complex Reactions.- II. Cell-Mediated (Delayed-Type) Reactions.- III. Reactions by Photosensitivity.- IV. Pseudoallergic Reactions.- 1. Mast Cell and Basophil Degranulation by Complement Components (Anaphylatoxins).- 2. Liberation of Histamine Through Nonimmunologic Mechanisms.- 3. Pseudoallergic Reactions to Drugs Interfering with Prostaglandin Synthesis.- E. Clinical Forms of Allergic Reactions to Drugs.- I. Anaphylactic Shock.- II. Serum Sickness.- III. Fever.- IV. Hematologic Reactions.- 1. Hemolytic Anemia.- 2. Agranulocytosis.- 3. Thrombocytopenia.- 4. Eosinophilia.- V. Hepatic Disorders.- VI. Renal Diseases.- VII. Reactions Affecting the Respiratory Tract.- 1. Asthma.- 2. Infiltrative and Fibrotic Pulmonary Reactions.- VIII. Drug-Induced Autoimmunity.- IX. Vasculitis.- X. Digestive Tract and Other Manifestations.- XI. Skin Manifestations.- References.- 4 Cutaneous Manifestations of Drug Allergy.- A. Pathogenesis and Classification.- I. Anaphylaxis, Urticaria, Angioedema.- II. Late Urticarial Reactions.- III. Serum Sickness.- IV. Maculopapular Rashes.- V. Erythema Multiforme and Stevens-Johnson Syndrome.- VI. Allergic Vasculitis.- VII. Erythema Nodosum.- VIII. Purpura.- IX. Purpura Pigmentosa Progressiva.- X. Fixed Eruptions.- XI. Lyell's Syndrome (Toxic Epidermal Necrolysis).- XII. Drug-Induced Lupus Erythematosus.- XIII. Allergic and Photoallergic Contact Dermatitis.- B. Diagnosis of Allergic Drug Reactions Involving the Skin.- References.- 5 Allergy of the Respiratory Tract to Low Molecular Weight Chemical Agents.- A. Introduction.- B. Inorganic Chemicals.- I. Halide Complex Salts of Platinum.- 1. Allergy to Complex Platinum Salts.- 2. Immunochemical Analysis of Allergenicity of Platinum Salts.- 3. Inhalation Tests with Platinum Salts.- 4. Serological Findings.- II. Nickel Sulphate.- III. Allergy to Potassium and Sodium Persulphate.- C. Chemical Organic Dusts.- I. Amprolium Hydrochloride.- II. Chloramine-T.- III. Piperazine Hydrochloride.- IV. Antibiotic Dusts: Ampicillin, Benzylpenicillin, 6-Aminopenicillanic Acid and Related Substances.- V. Salbutamol.- VI. Azo and Anthraquinone Dyes.- D. Organic Chemical Fumes and Vapours.- I. Aminoethylethanolamine.- II. Diisocyanates.- 1. Reactions to Diisocyanates Other than TDI.- 2. Modes of Action of TDI.- 3. Antibodies to Other Diisocyanates.- III. Epoxy Resin System Activating Agents.- 1. Phthalic Anhydride-Specific IgE Antibodies.- 2. Trimellitic Acid-Specific IgE and IgG Antibodies.- IV. Miscellaneous Agents.- E. General Comments.- References.- 6 Epidemiology of Drug Allergy: Drug Monitoring.- With 3 Figures.- A. Introduction.- B. Methods of Epidemiology and Drug Monitoring.- I. Comprehensive Inpatient (Intensive) Drug Monitoring.- 1. Euler-Venn Diagram.- 2. Weighted Attributions.- II. Outpatient Drug Monitoring.- III. Spontaneous Reporting of Adverse Reactions to Drugs.- IV. Use of Record Linkage for Drug Surveillance.- C. The Patient.- I. Disposition.- 1. Allergy to Small Molecular Drugs.- 2. Atopy and Adverse Drug Reactions: Drug Allergies.- 3. Idiosyncrasy.- 4. Intolerance.- II. Basic Diseases.- D. Criteria Important to Epidemiology and Drug Monitoring.- I. The Patient and the Adverse Reaction.- 1. Characteristics of Clinical and Laboratory Adverse Reactions: Distinction from Non-Drug Reactions.- 2. Definition of Clinical Syndromes and Laboratory Findings.- 3. Time Factors in Adverse Drug Reactions.- 4. Frequency of Adverse Drug Reactions.- 5. Degree of Importance of Adverse Drug Reactions.- 6. Outcome and Duration of Adverse Drug Reactions.- II. The Drug and Drug Groups.- 1. Different Kinds of Drugs.- 2. Method of Administration of Drug and Drug Allergic Reactions.- E. Practical Consequences.- F. Summary.- References.- 7 Diagnostic Proc…