Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions

Background Previous in vitro data indicate that perforin containing drug‐specific cytotoxic T cells are involved in cutaneous drug reactions. Objective The aim of this study was to investigate the in situ expression of perforin and granzyme B together with the nature of the inflammatory infiltrate in acute drug‐induced exanthem. Furthermore, expression of interleukin (IL)‐12 and interferon (IFN)‐γ, which are known to stimulate cytotoxic T cells, was investigated. Methods Skin biopsy specimens were obtained from 10 patients with a generalized maculopapular exanthem and from nine controls with normal skin. Expression of CD3, CD4, CD8, CD56, CD1a, CD68, CD25, HLA‐DR, CD54, perforin, granzyme B, IL‐12 and IFNγ was analysed using immunohistochemistry. Results In contrast to the controls, the skin of patients with an exanthem was mainly infiltrated by T cells (CD4 > CD8) and showed a marked enhancement of perforin and granzyme B immunostaining. Double immunostaining revealed that perforin and granzyme B were expressed in both CD4+ and CD8+ cells, which were partly located at the dermoepidermal junction and in the epidermis. In addition, strong immunreactivity for IL‐12 and IFNγ was observed in the mononuclear cells infiltrate, indicating that these cytokines may be important in activation of these cytotoxic T cells. Conclusion The increased numbers of perforin and granzyme B containing T cells infiltrating the dermoepidermal junction may contribute to the damage of epidermal cells, which is frequently observed as a typical feature of interface dermatitis in drug‐induced exanthem. Our data provide further evidence that cytotoxic T cells play an essential role in cutaneous drug reactions.