Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Concise Review with a Comprehensive Summary of Therapeutic Interventions Emphasizing Supportive Measures

Abstract

IntroductionStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe dermatologic conditions occurring in the inpatient setting. There is a lack of consensus regarding appropriate management of SJS and TEN.PurposeThe scientific literature pertaining to SJS and TEN (subsequently referred to as SJS/TEN) is summarized and assessed. In addition, an interventional approach for the clinician is provided.MethodsPubMed was searched with the key words: corticosteroids, cyclosporine, etanercept, intravenous immunoglobulin, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The papers generated by the search, and their references, were reviewed.ResultsSupportive care is the most universally accepted intervention for SJS/TEN. Specific guidelines differ from the care required for patients with thermal burns. Adjuvant therapies are utilized in most severe cases, but the data are thus far underwhelming and underpowered. Using systemic corticosteroids as sole therapy is not supported. A consensus regarding combined corticosteroids and intravenous immunoglobulin (IVIG) has not been reached. Data regarding IVIG, currently the standard of care for most referral centers, is conflicting. Newer studies regarding cyclosporine and tumor necrosis factor inhibitors are promising, but not powered to provide definitive evidence of efficacy. Data regarding plasmapheresis is equivocal. Thalidomide increases mortality.ConclusionClinicians who manage SJS/TEN should seek to employ interventions with the greatest impact on their patients’ condition. While supportive care measures may seem an obvious aspect of SJS/TEN patient care, providers should understand that these interventions are imperative and that they differ from the care recommended for other critically ill or burn patients. While adjuvant therapies are frequently discussed and debated for hospitalized patients with SJS/TEN, a standardized management approach is not yet clear based on the current data. Therefore, until further data are available, decisions regarding such treatments should be made on a case-by-case basis.

Efficacy and safety of cyclosporine in Stevens-Johnson syndrome and toxic epidermal necrolysis

“…While the exact mechanism of SJS and TEN remains unclear, perforin, granzyme B, and granulysin are considered "key mediators" in its pathogenesis (Schneider & Cohen, 2017). Studies have demonstrated that by inhibiting these mediators and reducing their expression, cytotoxicity is diminished (Chung, Wang, & Dao, 2016;Nassif et al, 2002).…”

“…Studies have demonstrated that by inhibiting these mediators and reducing their expression, cytotoxicity is diminished (Chung, Wang, & Dao, 2016;Nassif et al, 2002). Nuclear factor-κB is then inhibited, thus halting apoptosis and stopping the disease process (Schneider & Cohen, 2017;Stern & Divito, 2017). Cyclosporine inhibits the early phases of activation of CD4+ and CD8+ T cells, which subsequently inhibits the secretion of granulysin, granzyme, and perforin.…”

The use of etanercept for treatment of toxic epidermal necrolysis when toxic shock syndrome is in the differential

“…Recent studies have found that levels of TNF‐alpha are also upregulated in the pathogenesis of SJS/TEN, inducing keratinocyte apoptosis (Paradisi et al, ). TNF‐alpha inhibitors such as infliximab and particularly etanercept have been reported as treatment options for SJS/TEN and are thought to prevent disease progression and increase survival (Paradisi et al, ; Schneider & Cohen, ). With TNF‐alpha playing a role in the pathogenesis of both TSS and SJS/TEN, etanercept, a TNF‐alpha inhibitor, may be a reasonable treatment option for cases where prompt treatment is desired but diagnosis is uncertain.…”

Preparation of Amniotic Membrane and It’s Application in the Treatment of Skin Loss and Lyell's Syndrome (Toxic Epidermal Necrolysis): Current State and New Opportunities

“…Mortality can be even higher in elder patients and patients in whom the area of skin necrolysis is large [25]. Although systemic interventions may change the clinical course of this disease, local supportive therapy increases the survival rate and accelerates wound healing (Figure 4) [28].…”