Assessment of Treatment Approaches and Outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy.OBJECTIVE To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. DESIGN, SETTING, AND PARTICIPANTSA retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. MAIN OUTCOMES AND MEASURESRisk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. RESULTSOf 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (Ն30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups.CONCLUSIONS AND RELEVANCE This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.

Scoring Assessments in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

“…In a systematic review of the efficacy of intravenous immunoglobulin in the treatment of epidermal necrolysis, clinical endpoints were defined as mortality rates, length of hospital stay, time to disease cessation, and time to skin healing ( 30 ). A recent European multicenter study sought to assess overall treatment approaches including supportive care only as the reference group and the treatment groups were systemic glucocorticoids, cyclosporine, intravenous immunoglobulin, and antitumor necrosis factor agents ( 2 ). This study classified outcomes as risk of infection, body surface area detachment in the acute phase, and an overall 6-week mortality rate between treatment groups ( 2 ).…”

“…A recent European multicenter study sought to assess overall treatment approaches including supportive care only as the reference group and the treatment groups were systemic glucocorticoids, cyclosporine, intravenous immunoglobulin, and antitumor necrosis factor agents ( 2 ). This study classified outcomes as risk of infection, body surface area detachment in the acute phase, and an overall 6-week mortality rate between treatment groups ( 2 ). Furthermore, participants were also evaluated for long-term outcomes defined as the development of severe acute complications which included septicemia, acute kidney injury, pulmonary infection, or respiratory distress requiring mechanical ventilation ( 2 ).…”

“…This study classified outcomes as risk of infection, body surface area detachment in the acute phase, and an overall 6-week mortality rate between treatment groups ( 2 ). Furthermore, participants were also evaluated for long-term outcomes defined as the development of severe acute complications which included septicemia, acute kidney injury, pulmonary infection, or respiratory distress requiring mechanical ventilation ( 2 ). While some of these outcomes are standard clinical outcomes including complicating infections, others are more specific to the disease and lack the validation to confirm their utility such as time to disease cessation, skin healing, and body surface area detachment in the acute phase.…”

Disease severity and status in Stevens–Johnson syndrome and toxic epidermal necrolysis: Key knowledge gaps and research needs

“…Body surface area as the sole determinant of severity Body surface area has an important, validated, and clinically obvious association with in-hospital and early mortality (17,18).…”

Effectiveness and Safety of Early Short-Course, Moderate- to High-Dose Glucocorticoids for the Treatment of Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis: A Retrospective Study

“…The expected mortality rate was 21.1%; the actual mortality rate was 14.7%, and the hospitalisation period was 21.9 days. A European multicentre study 17 included a total of 212 patients (25 Asians) suffering from SJS/TEN, 35.4% of whom were treated with systemic glucocorticoids. 26.4% received gamma globulin/cyclosporine/TNFα; 38.2% received symptomatic and supportive treatment, and the six-week mortality rate was 20.8%.…”