Glutathione-S-Transferase Pi Expression in Toxic Epidermal Necrolysis: A Marker of Putative Oxidative Stress in Keratinocytes

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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 π (GST-π) 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-π in keratinocytes of TEN, other cutaneous adverse drug reactions and bullous pemphigoid. Results: GST-π was disclosed in the involved epidermis of 16/16 TEN patients. It was present in the cytoplasm of suprabasal keratinocytes. GST-π 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-π. GST-π expression is an early event in TEN. As oxidative stress is a major inducer of GST-π, this mechanism might be involved in TEN. Its GST-π 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.