Increased mortality in toxic epidermal necrolysis with thalidomide: corroborating or exonerating the pathogenetic role of TNF-α ?

Abstract

Conflicts of interest: none declared. Sir, I read with great interest the article by Chave et al.,1‘Toxic epidermal necrolysis: current evidence, practical management and future directions’, which appeared in the August 2005 issue of the British Journal of Dermatology. Referring twice to a randomized, placebo‐controlled study by Wolkenstein et al.2 showing increased mortality in toxic epidermal necrolysis (TEN) with the use of thalidomide, a TNF‐α inhibitor, Chave et al. support the notion that TNF could be antiapoptotic in this condition. However, the referenced work is not supportive of this notion at all—in fact, it supports the opposite notion, i.e. the pathogenetic involvement of TNF in TEN. Wolkenstein et al.’s data suggest that thalidomide does not inhibit TNF‐α production in TEN, rather, it might result in the paradoxical overproduction of it. In this study, plasma concentrations of this cytokine tended to increase after treatment with thalidomide in comparison with the placebo group. A similar unexpected increase in TNF‐α has been observed in the thalidomide therapy of oral aphthous ulcers in patients with human immunodeficiency virus infection.3