Drug Hypersensitivity Reactions

Introduction — what drug allergy is

• Definition — drug allergy (drug hypersensitivity) is an immunologically-mediated reaction to a drug, producing stereotyped symptoms that are unrelated to the drug's pharmacodynamic profile; it may appear with much smaller doses and follow a different time-course of onset and duration from the drug's pharmacological effects.
• Not supersensitivity — "hypersensitivity" here means an immune over-reaction — it must not be conflated with supersensitivity (an increased pharmacodynamic response). It is a subset of Type B (bizarre, unpredictable) adverse reactions: patient-dependent, often non–dose-related, generally more serious, and usually requiring drug withdrawal.
• Cardinal features — manifestations resemble classic allergic disease (urticaria, angioedema, asthma, anaphylaxis, serum sickness, contact dermatitis); severity correlates poorly with dose; they occur in only a small proportion of recipients and cannot be reproduced in non-sensitised individuals; positive dechallenge and rechallenge are characteristic.
• Prior sensitisation is mandatory — a latent period of at least 1–2 weeks after first exposure is needed before allergy can manifest; the sensitising exposure may be unnoticed or environmental (e.g. dietary/occupational penicillin).
• Target organs — skin, airways, blood vessels, blood cells and the gastrointestinal tract are principally affected.