Ethosuximide-induced lupus erythematosus: Unveiling a rare adverse reaction through systematic review

Ethosuximide (ESM) is a first-line anti-seizure medication (ASM) for absence seizures and is generally well-tolerated. However, rare immune-mediated adverse reactions like drug-induced lupus erythematosus (DILE) have been reported. This study aimed to systematically review published reports of ESM-induced lupus erythematosus (LE).

A comprehensive search of databases and sources was conducted up to June 2025 to identify eligible case reports and case series. Inclusion was based on predefined diagnostic criteria for DILE. The methodological quality of included studies was appraised using the Joanna Briggs Institute (JBI) checklists. Extracted data included publication characteristics, patient demographics, clinical features, laboratory findings, management, and outcomes.

Twenty-eight publications encompassing 47 patients met inclusion criteria. The median age was 9 years, and 70.4% were female. Most patients presented with systemic manifestations such as arthralgia, fever, rash, and arthritis, with occasional renal and central nervous system involvements. Antinuclear antibodies (ANA) were positive in 95% of cases, typically at high titers with a homogeneous pattern. Anti-histone antibodies, characteristic of DILE, were detected in over 85% of tested patients, while anti-dsDNA antibodies were also reported in a notable subset. Discontinuation of ESM led to marked clinical improvement in 80% of patients, with or without adjunctive corticosteroids.

ESM-induced LE, though exceedingly rare, should be suspected in patients on ESM presenting with systemic autoimmune features. Its clinical and serological profiles overlap those of idiopathic systemic lupus erythematosus and classic DILE. Early recognition and prompt discontinuation of ESM typically result in rapid remission and may prevent unnecessary prolonged immunosuppression.