A Systematic Review of Literature: TNF‐α Blockers and JAK Inhibitors for the Treatment of Stevens‐Johnson Syndrome, Toxic Epidermal Necrolysis, and Severe Forms of Erythema Multiforme

Background and Aims Stevens‐Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and erythema multiforme major (EM major) are severe dermatologic conditions characterized by varying degrees of skin detachment and involvement of mucosal membranes, often triggered by drug reactions or infections. The management of these conditions poses a significant challenge due to the potential for rapid progression to life‐threatening complications. Recently, emerging therapeutic approaches such as Tumor Necrosis Factor‐alpha (TNF‐α) blockers and Janus Kinase (JAK) inhibitors have shown promise in regulating the dysregulated immune response implicated in these disorders. A comprehensive literature review was conducted to evaluate the efficacy and safety of TNF‐α blockers and JAK inhibitors in treating SJS, TEN, and EM. Methods A systematic review was conducted according to PRISMA guidelines. A comprehensive literature search was performed in PubMed, Scopus, Embase, Web of Science, and Google Scholar, up to September 5, 2025, on JAK inhibitors and TNF inhibitors in treating SJS, TEN, or EM major. Results The current review studies 82 articles (748 patients), including case reports, cohort studies, and clinical trials. Various JAK inhibitors and TNF inhibitors, such as tofacitinib, etanercept, adalimumab, and infliximab, were assessed regarding effectiveness in treating SJS/TEN and EM. Notably, some cases demonstrated a rapid response to these inhibitors, resulting in faster re‐epithelialization and a reduction in the severity of lesions. Conclusion TNF‐α blockers like infliximab and etanercept show promise for patients unresponsive to standard treatments, shortening acute phases, reducing hospitalization, and mortality rates, and enhancing healing. Further research, especially registry‐based studies, is crucial. Healthcare practitioners are advised to exercise caution and reserve novel drugs for managing hypersensitivity reactions.