DRUG-INDUCED HYPERSENSITIVITY SYNDROMES

Hypersensitivity syndromes are severe drug induced side effects with s kin rashes, fever and/or multiorgan-system abnormalities which are not pharmacologically related. They are well known in relation to allopur inol, anticonvulsants and sulfonamides, but only rarely described with other drugs. These reactions are considered to be immune-mediated but the precise mechanisms are not completely understood. Clinical featur es, which resemble an EBV infection, and some immunological studies su ggest that T-cell mediated immunity is involved in the pathogenesis of this rare disease. In the literature, allopurinol and anticonvulsant hypersensitivity syndromes are clinically well characterized entities, while the definition of hypersensitivity syndrome elicited by other d rugs is rather confusing. We present two patients, one with sulfometho xazole- and one with allopurinol-induced hypersensitivity syndrome. In both cases a lymphocyte transformation test (LTT) was performed and w e analyzed the T-cell activation parameters CD25 and HLA-DR on CD4(+) and CD8(+) T-cells to demonstrate in vivo activation of T-cells during the active disease. Both patients show increased activation of T-cell s with elevated levels of HLA-DR on CD8(+) cells. The T-cell activatio n correlated with the clinical course. Our data support an immunologic al pathogenesis for hypersensitivity syndromes and the concept that dr ug specific T-cells are involved in hypersensitivity syndromes.