Objective: Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE). However, so far, relatively few and small size-based studies have been conducted. We aimed to investigate the link between seizure and SLE utilizing a large sample of subjects and extensive data analysis. Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of epilepsy in a cross-sectional study. Chi-square and t tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. Results: The study included 5,018 patients with SLE and 25,090 age- and gender-frequency-matched controls. The proportion of epilepsy was found significantly higher among SLE patients (4.03 vs. 0.87%, p < 0.001). Using logistic regression, adjusting for multiple confounding factors, older age (≥70 years) resulted as negative predictor (OR 0.42 [95% CI 0.27–0.62], p <0.001), whereas the presence of SLE was a positive predictor of epilepsy (OR 4.70 [95% CI 3.94–5.82], p < 0.001). Interaction between SLE and elderly age resulted in high OR of 5.47 for epilepsy (95% CI 2.53–11.9). Conclusion: Our study confirms the higher prevalence of epilepsy in SLE patients. Physicians should be aware of such findings and have a lower threshold for suspecting epileptic seizures in these patients. Further studies are needed to better elucidate the mechanisms by which SLE favors the insurgence of seizures.

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