Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis in a cohort of patients

Background: Systemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged because of their limited benefits. Whether additional tumor necrosis factor (TNF) alpha inhibition provides an optimized approach remains unexplored. Objective: To investigate the efficacy of TNF-alpha inhibition combined with a steroid to treat SJS/TEN and to identify potential biomarkers. Methods: Twenty-five patients with SJS/TEN were recruited and divided into 2 groups: 10 patients received methylprednisolone and 15 patients received etanercept plus methylprednisolone. Serum levels of granzyme B, perforin, interferon-gamma, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1 alpha, macrophage inflammatory protein 1 beta, and TNF-alpha were measured by multiplex cytokine analysis kits during the acute and resolution phases. Results: Compared with the steroid monotherapy, the combination therapy significantly shortened the course of the initial steroid treatment and the duration of the acute stage, hospitalization stay, and skin reepithelialization. Although both therapies significantly reduced IL-15 levels; the combination therapy also decreased IL-6 and IL-18 levels. While the level of IL-15 was positively correlated with skin reepithelialization time in both groups, the level of IL-6 served as an additional marker for the course of the disease in the combination therapy group. Limitations: The cohort size is relatively small. Conclusion: Additional TNF-alpha inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.