Antiseizure drug-induced Stevens - Johnson syndrome and toxic epidermal necrolysis in children: a systematic review

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe reactions associated with antiseizure drugs (ASDs). This systematic review aimed to summarize the clinical characteristics, implicated drugs, management strategies, and outcomes of ASD-induced SJS/TEN in children. METHODS: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar from database inception to 2025 following PRISMA 2020 guidelines. Descriptive studies reporting pediatric patients (≤18 years) with ASD-induced SJS, TEN, or SJS-TEN overlap were included. RESULTS: Thirty-four studies involving 37 pediatric patients were included. Among them, 22 patients (59.5%) developed SJS, 10 (27.0%) TEN, 4 (10.8%) SJS-TEN overlap, and 1 (2.7%) overlapping SJS/DRESS. Patients were aged 2.25-18 years, with males accounting for 20 (54.0%) of cases and females for 17 cases (45.9%). Lamotrigine was the most commonly implicated ASD (43.2%), followed by valproic acid (35.1%), and phenytoin and phenobarbitone (16.2% each). Monotherapy was reported in 64.8% of patients, while dual and triple therapy occurred in 27% and 8.1%, respectively. The lamotrigine-valproic acid combination was the most frequent high-risk regimen (21.6%). Most reactions occurred within 1-3 weeks of treatment initiation or dose escalation, especially during rapid titration. Drug withdrawal, supportive care, corticosteroids, and intravenous immunoglobulin were the main treatment strategies. Most patients recovered, although 1 death (2.7%) was reported. CONCLUSION: ASD-induced SJS/TEN in children is rare but serious. Lamotrigine was the most frequently implicated ASD, with several cases occurring during early treatment or dose escalation, particularly in valproate-containing regimens. These findings reinforce the importance of cautious prescribing, appropriate titration, early recognition, and prompt withdrawal of the suspected drug.