P Paquet1, G E Piérard. 1. Department of Dermatopathology, University of Liège, Liège, Belgium. P.Paquet@chu.ulg.ac.be
Abstract
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. (c) 2007 S. Karger AG, Basel.
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. (c) 2007 S. Karger AG, Basel.