From the Cochrane Library: Systemic Interventions for Steven-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and SJS/TEN Overlap Syndrome

Introduction

Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are a spectrum of potentially life-threatening, rare, and severe cutaneous adverse reactions that are triggered by medication use typically within weeks of medication initiation. The pathogenesis of SJS/TEN is theorized to be a T lymphocyte–mediated immune response to an antigen of the offending medication causing epidermal necrosis [1]. There is limited evidence to support the use of therapies, such as glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporine, and etanercept, for the treatment of SJS and TEN [1]. We aim to summarize the key findings of a Cochrane review on the effects of systemic therapies for SJS/TEN.

Methods

To evaluate systemic therapies for SJS/TEN, a systematic review of randomized controlled trials (RCTs) and prospective observational comparative studies (up to March 2021) of patients of all ages with SJS/TEN was conducted [1]. The primary end points were disease-specific mortality (DSM) and adverse events leading to the discontinuation of systemic treatment therapy. Secondary end points included time to complete re-epithelialization, intensive care unit length of stay, total hospital length of stay, illness sequelae, and adverse events.

Results

In total, 9 studies with a total of 308 patients from across 7 countries were included in the analysis, of which 3 were RCTs and 6 were prospective observational studies; 2 studies were included in a meta-analysis. The risk of bias for the three RCTs was respectively rated as high, moderate, and low; all the prospective comparative studies were rated as having a high risk of bias. The interventions that were assessed included systemic corticosteroids, tumor necrosis factor-α inhibitors, and others (Table 1).

The overall level of certainty for the parameters of interest was low, so most findings were “uncertain.” It was uncertain if corticosteroids had a higher risk of DSM versus no corticosteroids (relative risk [RR] 2.55, 95% CI 0.72-9.03). It was also uncertain if there was a difference between IVIGs and no IVIGs in terms of DSM (RR 0.33, 95% CI 0.04-2.91), time to re-epithelialization (mean difference −2.93, 95% CI −4.4 to −1.46 d), or length of hospital stay (mean difference −2.00, 95% CI −5.81 to 1.81 d). Etanercept did not significantly reduce DSM compared to corticosteroids (RR 0.51, 95% CI 0.16-1.63; P=.72), and serious adverse events, such as sepsis and respiratory failure, occurred in treatment with both groups. It was also uncertain if there was any difference between the cyclosporine and IVIG groups in terms of the risk of DSM (RR 0.13, 95% CI 0.02-0.98). A summary of other comparator studies is included in Table 2.

Discussion

The authors of the original review concluded that “etanercept (25 mg [50 mg if weight > 65 kg]) twice weekly ‘until skin lesions healed’) may reduce DSM compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day ‘until skin lesions healed’) (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low‐certainty evidence); however, the CIs were consistent with possible benefit and possible harm” [1]. Overall, data from the included studies were limited, with few direct clinical comparator studies for the different therapeutic agents assessed. Future multicenter large-scale studies are needed to better outline SJS/TEN medication therapy and evaluate agents of choice in disease management.