DRUG-INDUCED STEVENS–JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS
Keywords:
Stevens–Johnson; toxic epidermal necrolysis; adverse drug reaction; pharmacovigilance; ALDEN; HLA; pharmacogeneticsAbstract
DOI: https://doi.org/10.46296/yc.v10i19.0989
Abstract
Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a continuum of severe adverse cutaneous reactions, predominantly drug-induced. Objective: To synthesize contemporary evidence regarding triggering drugs, susceptibility factors, clinical characteristics, and outcomes of drug-induced SJS/TEN. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Human studies published between January 2010 and April 30, 2026, were searched in PubMed/MEDLINE, Google Scholar, SciELO, and Scopus. Included studies comprised cohorts, case-control studies, clinical series of at least 10 patients, pharmacogenetic studies, and pharmacovigilance analyses with verifiable full text. Case reports, reviews, editorials, and studies lacking data separable for SJS/TEN were excluded. Due to heterogeneity in study design, exposure, and causality definitions, a structured narrative synthesis was performed. Results: Eighteen primary studies were included. Evidence consistently identified aromatic anticonvulsants and lamotrigine, antibiotics—particularly trimethoprim/sulfamethoxazole—allopurinol, and non-steroidal anti-inflammatory drugs (NSAIDs) as the most frequent triggers. In the FAERS database, lamotrigine, trimethoprim/sulfamethoxazole, allopurinol, and phenytoin accounted for a significant proportion of reports; analyses of antiepileptic drugs revealed disproportionately high signals, particularly for lamotrigine, phenytoin, and carbamazepine. Population-based studies linked the risk to advanced age, diabetes, peripheral vascular disease, autoimmune diseases, psoriasis, a history of drug allergy, malignancy, and epilepsy. The HLA-B*58:01 allele showed a strong association with allopurinol-induced SJS/TEN in the Korean population. Mortality varied widely depending on severity and level of care, ranging from approximately 6.9% to 46.7%, and was higher in cases of TEN, extensive skin detachment, sepsis, and high SCORTEN scores. Conclusions: Drug-induced SJS/TEN remains driven by a relatively stable group of high-risk medications, although signals associated with modern oncological therapies are emerging. Immediate withdrawal of the suspected drug, systematic causality assessment, and recognition of clinical or genetic susceptibility are essential to reduce morbidity and mortality.
Keywords: Stevens–Johnson; toxic epidermal necrolysis; adverse drug reaction; pharmacovigilance; ALDEN; HLA; pharmacogenetics.
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