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

• Published in: Chinese medical journal Vol. 137; no. 19; pp. 2294 - 2307
• Main Authors: Hasegawa, Akito, Abe, Riichiro
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 05.10.2024; Lippincott Williams & Wilkins Ovid Technologies; Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Wolters Kluwer
• Subjects: Age; Algorithms; Allopurinol - therapeutic use; Anti-inflammatory agents; Antibiotics; Apoptosis; Bacterial infections; Biomarkers; Biomarkers - metabolism; Carbamazepine - therapeutic use; Cardiac arrhythmia; Causality; Diabetes; Drug interactions; Fas Ligand Protein - metabolism; Glucose; Herpes viruses; HIV; Human immunodeficiency virus; Humans; Illnesses; Infections; Mortality; Review; Risk factors; Skin; Steroids; Stevens-Johnson Syndrome - diagnosis; Stevens-Johnson Syndrome - therapy; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Necroptosis; Apoptosis
• ISSN: 0366-6999; 2542-5641; 2542-5641
• DOI: 10.1097/CM9.0000000000003250

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.