Pathogenesis of Drug-Induced Exanthema

Abstract

Background: In vitro data derived from drug-specific T cell clones have revealed that heterogeneous T cell subsets with distinct phenotypes (CD4+ > CD8+) and cell functions (strong IL-5 production, cytotoxic potential) are generated. The aim of this study was to elaborate the relevance of these findings in vivo. Methods: Skin biopsy specimens from drug-induced maculopapular exanthema and normal skin were analyzed for CD4, CD8, CD25, HLA-DR, CD54, perforin, granzyme B, IL-5 and IFN-γ using immunohistochemistry. Results: The majority of infiltrating lymphocytes in maculopapular drug eruptions were CD4+. Both CD4+ and CD8+ T cells expressed perforin and granzyme B and were partly located at the dermoepidermal junction and in the epidermis. In addition, strong immunoreactivity for IL-5 and moderate immunoreactivity for IFN-γ were observed in the mononuclear cell infiltrate. Conclusions: Our data indicate that skin infiltrating T cells with a cytotoxic potential and the ability to produce IL-5 and IFN-γ may contribute to the damage of keratinocytes and the activation of eosinophils, which are typical features of drug-induced maculopapular exanthema.