Background: Although epidermal and dermal T cells play roles in the pathogenesis of fixed drug eruption (FDE), not much is known about keratinocyte death and its precise mechanism in FDE. Objectives: Our aim is to elucidate the mechanism that underlies keratinocyte death in FDE, that is, the role of apoptosis and its signalling pathway. Methods: We first examined the involvement of apoptosis in the active FDE lesions by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelli- ng (TUNEL) assay and immunohistochemical analysis of caspase-3. We then examined the expressions of Fas and Fas ligand (FasL) to deduce the possible upstream signalling pathway of apoptosis, if apoptosis were involved. We finally characterized the infiltrated T-cell subpopulations in the active FDE lesions. Results: In the active FDE lesions, TUNEL positivity was strongly observed in the basal keratinocytes, and also weakly observed in the upper dermal infiltrates as well as in a few keratinocytes in the granular layer. The distribution of TUNEL-positive cells was similar to that of the strong staining of active capase-3. Fas was found mainly in the keratinocytes and some infiltrated dermal cells, whereas FasL was identified predominantly in the intraepidermal and dermal infiltrated cells and in some basal keratinocytes. Overlapping expression of Fas and FasL was accompanied by apoptosis in the FDE lesions. Many of the infiltrated mononuclear cells were CD8+. Perforin was rarely observed in the FDE lesions. Conclusions: These findings suggest that apoptosis of the keratinocyte is highly likely to be involved in the pathogenesis of FDE, and this cytotoxicity might be predominantly mediated by the FasL of the infiltrating CD8+T cells, possibly also playing an inflammatory role.
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