Updates in SJS/TEN: collaboration, innovation, and community

**Background:** Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening, immunologically-mediated severe cutaneous adverse drug reactions (IM-ADRs) defined across a spectrum of severity based on body surface area (BSA) detachment: SJS (<10% BSA), SJS/TEN (10–30% BSA), and TEN (>30% BSA). Overall mortality is 15–20%, exceeding 50% in elderly and immunocompromised patients. Incidence is 1–5 cases per million persons annually in developed countries. More than 80% of adult cases are drug-related, with highest risks from aromatic antiepileptic drugs, sulfonamide antibiotics, and allopurinol. The disease is HLA class I-restricted CD8+ T-cell mediated.

**Methods:** This is a narrative review based on presentations and discussions from the virtual meeting "SJS/TEN 2021: Collaboration, Innovation, and Community." The paper synthesizes current knowledge on prevention, diagnosis, management, and future directions, incorporating data from published studies, consensus exercises, and patient surveys.

**Key Results:** - **Pharmacogenomics:** HLA-B*15:02 genotyping prior to carbamazepine administration is cost-effective in Southeast Asian populations (allele frequency 5–20%). Implementation in Hong Kong, Taiwan, Singapore, Thailand, and China has reduced carbamazepine-induced SJS/TEN. A multiple-variant panel for antiepileptic drugs showed 75% sensitivity and 90% specificity in a prospective observational study. - **Diagnosis:** SCORTEN remains the mainstay severity score; the newer CRISTEN score does not require laboratory values and was validated across 416 patients. BSA estimation is highly variable—a meta-analysis of 26 burn studies found an average error of 70%. Photography and artificial intelligence are proposed to improve accuracy. - **Eye Care:** Early amniotic membrane transplantation (AMT) significantly improves visual outcomes: 92% of patients receiving AMT retained >20/40 vision vs. 33% without. Vision-threatening complications were 17% vs. 67%. - **Supportive Care:** Transfer to specialized burn units is recommended early. Multidisciplinary teams including dermatology, ophthalmology, gynecology, urology, and psychiatry are essential. - **Long-term Complications:** 88.2% of survivors reported physical health impact; 70.2% felt physicians inadequately addressed complications. Ocular complications affect ~50% of survivors. Skin sequelae occur in 80%. - **Mechanisms:** Keratinocyte death involves apoptosis (Fas-FasL, granulysin) and necroptosis (annexin A1-FPR1 interaction, neutrophil extracellular traps).

**Clinical Implications:** Pre-prescription pharmacogenetic screening, particularly for HLA-B*15:02 and HLA-B*58:01, can prevent SJS/TEN in high-risk populations. Early diagnosis, immediate cessation of culprit drugs, and transfer to specialized centers are critical. Standardized eye care protocols including AMT within the first 7 days can dramatically improve visual outcomes. Multidisciplinary follow-up is needed to address long-term physical and mental health sequelae. International collaboration and diverse population studies are urgently needed to identify additional genetic risk factors and optimize treatment.