Drug Hypersensitivity Reactions: Gell-Coombs Classification

Drug hypersensitivity reactions are immune-mediated adverse drug reactions that are unpredictable, not dose-dependent (in contrast to pharmacological side effects), and require prior sensitization (except for some Type I reactions mediated by pre-existing cross-reactive IgE). The Gell-Coombs classification organizes these reactions into four types based on the immune mechanism: Type I — Immediate (IgE-mediated) hypersensitivity: The classic 'allergic' reaction. During initial exposure, the drug (or drug-protein hapten complex) stimulates B cells to produce drug-specific IgE antibodies, which bind to FcεRI receptors on mast cells and basophils (SENSITIZATION phase — no symptoms). Upon RE-EXPOSURE, the drug cross-links two adjacent IgE molecules on the mast cell surface, triggering immediate degranulation and release of preformed mediators (histamine, tryptase, prostaglandins, leukotrienes). Clinical manifestations occur within MINUTES to 1 HOUR: urticaria (hives), angioedema, bronchospasm, and in the most severe form, anaphylaxis (cardiovascular collapse, laryngeal edema, distributive shock). Most common causative drugs: beta-lactam antibiotics (penicillins, cephalosporins — the most common cause of drug-induced anaphylaxis), NSAIDs (via COX-1 inhibition causing leukotriene shunting — technically a pseudoallergic mechanism, not IgE-mediated), neuromuscular blocking agents, and latex. Type II — Cytotoxic...