Stevens-Johnson syndrome and toxic epidermal necrolysis: Updates in pathophysiology and management

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions characterized by extensive detachment of the epidermis and mucous membranes. These severe disorders carry a high mortality rate, and their pathogenesis remains largely unclear. Furthermore, optimal therapeutic strategies for SJS/TEN remain a subject of ongoing debate. Early diagnosis of SJS/TEN is challenging, and reliable biomarkers for diagnosis or severity prediction have not been firmly established. Certain drugs, such as carbamazepine and allopurinol, have shown a strong association with specific human leukocyte antigen (HLA) types. Recently, the potential benefits of HLA screening prior to administering these drugs to reduce the incidence of SJS/TEN have been explored. Epidermal cell death in SJS/TEN lesions is caused by extensive apoptosis, primarily through the Fas-Fas ligand (FasL) and perforin/granzyme pathways. Our findings suggest that necroptosis, a form of programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, interacts with the formyl peptide receptor 1 to induce necroptosis. Several biomarkers, such as CC chemokine ligand (CCL)-27, interleukin-15, galectin-7, receptor-interacting protein kinases 3 (RIP3), and lipocalin-2, have been identified for diagnostic and prognostic purposes in SJS/TEN. Supportive care is recommended for treating SJS/TEN, but the efficacy of various therapeutic options-including systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and tumor necrosis factor-α antagonists-remains controversial. Recent studies have investigated the potential benefits of tumor necrosis factor-α antagonists. In this review, we discuss recent advances in the understanding and management of SJS/TEN.