Fixed drug eruptions: evidence for a cytokine-mediated process

Fixed drug eruptions (FDE) are immunologic reactions to drugs which produce erythematous plaques or blisters that characteristically recur at the same cutaneous sites with repeated antigenic challenges. While a detailed pathogenesis of these lesions remains obscure, T-lymphocyte infiltration has been documented repeatedly. In this study, we tried to determine if FDE were mediated, at least in part, by cytokines, such as gamma-interferon. We examined biopsies from 6 cases of clinically well-documented FDE with an HLA-DR antibody, LN3, and an antibody to gamma IP-10 (IP-10), a protein expressed by keratinocytes, monocytes, lymphocytes and endothelial cells following exposure to gamma-interferon. We found staining of the dermal lymphocytes with anti-HLA-DR antibody in all 6 cases examined. Keratinocytes and endothelial cells showed only focal staining at the antibody concentrations used. In addition, there was keratinocyte staining with the IP-10 antibody at all levels of the epidermis, with accentuation in areas of blister formation. There was more intense staining of keratinocytes with the IP-10 antibody in cases with accumulations of HLA-DR positive lymphocytes in the dermis. We believe that these findings are consistent with the hypothesis that FDE represent cell-mediated immunologic responses to a variety of antigens, and further, that the histologic alterations can be explained, at least in part, by a cytokine-mediated process.