[Drug-induced hypersensitivity syndrome. A review and presentation of 2 personal cases]

Hypersensitivity syndromes are severe drug induced side effects with skin rashes, fever and/or multiorgan-system abnormalities which are not pharmacologically related. They are well known in relation to allopurinol, 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 features, which resemble an EBV infection, and some immunological studies suggest 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 drugs is rather confusing. We present two patients, one with sulfamethoxazole- and one with allopurinol-induced hypersensitivity syndrome. In both cases a lymphocyte transformation test (LTT) was performed and we 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-cells with elevated levels of HLA-DR on CD8+ cells. The T-cell activation correlated with the clinical course. Our data support an immunological pathogenesis for hypersensitivity syndromes and the concept that drug specific T-cells are involved in hypersensitivity syndromes.