210 - Hypersensitivity to antibiotics

Summary

Adverse drug reactions (ADRs) are usefully separated into type A reactions (predictable from known pharmacologic properties and largely dose related) and type B reactions (unpredictable and restricted to a vulnerable subpopulation). Type B reactions comprise 10% to 15% of all ADRs and include immunologic drug reactions, drug intolerance (e.g., tinnitus after single aspirin tablet), and idiosyncratic reactions, some of which are pseudoallergic (e.g., aspirin-induced reactions).

Immune mechanisms are thought to be involved in 6% to 10% of all ADRs. Allergenic drugs can induce the entire spectrum of immunopathologic reactions, which are clinically indistinguishable from reactions elicited by foreign macromolecules (Table 210.1). Gell and Coombs’ type I reactions are caused by drug/antigen-specific immunoglobulin E (IgE) that binds to high-affinity Fc-IgE receptors on mast cells and basophils. Cross-linking of these receptors leads to the release of vasoactive mediators such as histamine and cysteinyl leukotrienes. Typical syndromes include urticaria, anaphylaxis, rhinitis, and bronchoconstriction, which can occur immediately in a previously sensitized individual. Type II cytolytic reactions are generally confined to rapidly haptenating drugs such as penicillins and are based on immunoglobulin G (IgG)-mediated cytotoxic mechanisms, resulting mainly in blood cell cytopenias. Type III reactions are immune complex mediated and may involve complement activation and stimulation of Fc-α receptor-activated inflammatory cells. Drug-specific immune complexes result from high-dose, prolonged therapy and may produce drug fever, a classic serum sickness syndrome, and various forms of cutaneous vasculitis. Type IV reactions are mediated by T lymphocytes and cause “delayed hypersensitivity reactions,” the most typical examples being delayed maculopapular exanthem and contact dermatitis from topically applied drugs. Many drug-induced hypersensitivity reactions such as bullous, pustular, and some morbilliform skin eruptions that are presumed to have an immune etiology did not seem to fit into the older Gell and Coombs classification. Recent studies of T-cell subsets and functions in the pathogenesis of delayed-onset immune reactions have suggested subcategories of type IV reactions as shown in Table 210.1.