Abstracts

Rationale: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a multifactorial pathogenesis, including genetic, epidemiologic, and environmental factors. Certain drugs can also trigger SLE, and these agents may unmask clinically silent SLE, and induce flares or lupus like syndromes. Collectively, these syndromes are referred to as drug-induced lupus (DIL). DIL, by definition, resolves after discontinuation of the offending drug, although in most cases its complete resolution can take weeks to months. Irreversibility of symptoms after discontinuation of the offending drug usually underlies a pre-existing SLE that was simply unmasked by the drug.

Anti-seizure medications historically associated with DIL include carbamazepine, primidone and phenytoin. Associations with other drugs such as ethosuximide are increasingly being recognized. Ethosuximide is currently classified under the very low risk category (0.1%), but with an increasing number of cases reported. Literature in children is limited to only a handful of case reports, and more research is needed in the pediatric population to create awareness as risk might be higher than currently established.


Methods: A single-center retrospective study was conducted on pediatric patients with epilepsy who developed lupus-like symptoms while taking ethosuximide. We describe the demographics, clinical presentation, autoantibody profile, management and patient outcomes.
We compare cases that had resolution of symptoms after discontinuation of Ethosuximide with cases that developed persistent SLE.


Results:

Ten patients were identified, 50% with DIL and 50% with SLE. The median age was 5 years (range: 2-12 years). Female (80%) and Hispanic (70%). The most common indication for ethosuximide was Childhood Absence Epilepsy (60%). The median ethosuximide dose was 22 and 24 mg/kg/day in the DIL and SLE groups respectively. Median blood ethosuximide level was higher in the SLE group (106 mcg/mL) compared to the DIL group (49 mcg/mL).

Symptoms at presentation were similar in both groups with arthralgias (60%) and gastrointestinal symptoms (40%) being the most common. The median time from the start of ethosuximide to symptom onset in DIL was 2.25 months (range: 0.25-12 months), compared to 12 months (range: 3-72 months) in SLE. Autoantibodies present were Anti-Histone (100%), ANA (80%), and Anti-dsDNA (70%). Two-thirds of those diagnosed with DIL had positive dsDNA antibodies that later became negative.




Ethosuximide was discontinued in all patients, and symptoms resolved in those diagnosed with DIL. However, 90% of patients diagnosed with SLE continued to experience flares and remained on chronic immunosuppression, consistent with SLE diagnosis.






Conclusions: Children presenting with lupus-like symptoms while taking ethosuximide should be evaluated for drug-induced lupus (DIL). Ethosuximide can also unmask clinically silent systemic lupus erythematosus (SLE) and screening for SLE and referral to rheumatology for evaluation is recommended. The association noted in Hispanic patients needs further investigation and pharmacogenomic studies.

Funding: No funding was received in support of this abstract.