Logo image
Back
Proportion of Antiepileptic Drug-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis A Meta-Analysis
Journal article   Open access   Peer reviewed

Proportion of Antiepileptic Drug-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis A Meta-Analysis

Erika Yue Lee, Christopher Knox, Cinthiya Sugumar and Elizabeth Jane Phillips
JAMA dermatology (Chicago, Ill.)
2026
DOI: https://doi.org/10.1001/jamadermatol.2026.2473
PMID: 42485011
pdf
Toxic Epidermal Necrolysis359.64 kBDownloadView
Open Access CC BY-NC-ND V4.0

Abstract

Dermatology Life Sciences & Biomedicine Science & Technology
Importance Antiepileptic drugs (AEDs) are frequently implicated in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are the most severe type of drug hypersensitivity reaction, with a mortality rate up to 50%. However, the overall proportion of these cases attributed to AEDs has not been systematically reviewed. Objective To evaluate the proportion of AED-associated SJS/TEN. Data Sources The MEDLINE and Embase databases were searched from inception through March 17, 2026, with results limited to English-language publications and human participants. Study Selection All experimental and observational studies that reported patient-level triggers of SJS/TEN were included. Data Extraction and Synthesis Two reviewers independently screened studies and extracted data using a predefined template. To estimate the proportion of AED-associated SJS/TEN, a random-effects meta-analysis was performed, calculating the pooled proportions with 95% CIs. Subgroup analyses by age group (children vs adults) and geographic region were performed to explore heterogeneity. Main Outcomes and Measures To estimate the proportion of AED-associated SJS/TEN. Results This systematic review and meta-analysis included 50 studies with 4403 patients that reported patient-level triggers of SJS/TEN. Single-drug triggers accounted for 88% (95% CI, 83-92) of cases. The pooled proportion of SJS/TEN cases attributed to AEDs was 23% (95% CI, 19-26). Nearly all AED-associated cases were due to aromatic AEDs (96%; 95% CI, 92-99), most commonly carbamazepine (39%; 95% CI, 29-50), followed by phenytoin (19%; 95% CI, 11-28), and lamotrigine (15%; 95% CI, 8-22). Nonaromatic AEDs were rarely implicated (2%; 95% CI, 0-4). Significant geographic variation was observed in the proportion of AED-associated SJS/TEN, ranging from 42% (95% CI, 26-59) in West Asia to 10% (95% CI, 0-33) in Africa (P < .001). The proportion of AED-associated SJS/TEN cases was significantly higher in children (35%; 95% CI, 22-48) than in adults (23%; 95% CI, 20-27). Conclusions and Relevance In this systematic review and meta-analysis of observational studies, AEDs accounted for nearly one-quarter of SJS/TEN cases reported worldwide, predominantly involving aromatic AEDs, such as carbamazepine, phenytoin, and lamotrigine. These findings suggest aromatic AEDs as leading contributors to SJS/TEN and support the preferential use of nonaromatic AEDs when clinically appropriate.

Details

Metrics

1 Record Views
Logo image