Glutathione-S-transferase pi expression in toxic epidermal necrolysis: a marker of putative oxidative stress in keratinocytes.

BACKGROUND Toxic epidermal necrolysis (TEN) is a dramatic drug-induced emergency related to extensive destruction of the epidermis. There is evidence that its pathomechanism involves impaired detoxication of xenobiotics. Glutathione-S-transferase pi (GST-pi) is a phase II detoxifying enzyme involved in drug metabolization by human keratinocytes. METHOD Immunohistochemistry was performed in order to assess the expression of GST-pi in keratinocytes of TEN, other cutaneous adverse drug reactions and bullous pemphigoid. RESULTS GST-pi was disclosed in the involved epidermis of 16/16 TEN patients. It was present in the cytoplasm of suprabasal keratinocytes. GST-pi was also expressed in the clinically uninvolved skin in a majority (8/12) of TEN patients. By contrast, it was rarely and poorly expressed in the other tested dermatoses. CONCLUSION The pathomechanism of TEN is not related to an impaired quantitative expression of GST-pi. GST-pi expression is an early event in TEN. As oxidative stress is a major inducer of GST-pi, this mechanism might be involved in TEN. Its GST-pi expression mainly restricted to the suprabasal keratinocytes suggests that the pathomechanisms leading to keratinocyte death in TEN are distinct at different levels of the epidermis.