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

Abstract

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) α inhibition provides an optimized approach remains unexplored.

Objective: To investigate the efficacy of TNF-α 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-γ, interleukin (IL) 6, IL-15, IL-18, macrophage inflammatory protein 1α, macrophage inflammatory protein 1β, and TNF-α 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 re-epithelialization. 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 re-epithelialization 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-α inhibition to steroid treatment appeared to improve outcomes for SJS/TEN.

Keywords: Stevens-Johnson syndrome; TNF-α inhibition; biomarker; cytokine; interleukin 15; interleukin 6; toxic epidermal necrolysis.