RANDOMIZED COMPARISON OF THALIDOMIDE VERSUS PLACEBO IN TOXIC EPIDERMAL NECROLYSIS

Background Toxic epidermal necrolysis (TEN) is associated with a 30% d eath rate. Tumour necrosis factor alpha (TNF-alpha) has been implicate d in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF -a action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN. Methods The patients received a 5-day course o f thalidomide 400 mg daily or placebo. The main endpoint was the progr ession of skin detachment after day 7. Secondary endpoints were the se verity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were meas ured. Findings The study was stopped because there was excess mortalit y in the thalidomide group-ten of 12 patients died compared with three of ten in the placebo group (Fisher's exact test with Katz's approxim ation, relative risk = 2.78, p = 0.03). After adjustment for SAPS, mor tality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p = 0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was highe r in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p = 0.07), Int erpretation Even though few patients were included, our data suggest t hat thalidomide is detrimental in TEN, possibly because of a paradoxic al enhancement of TNF-a production.