Updates in Neuropsychiatric Systemic Lupus Erythematosus: Advances in Pathogenesis, Diagnosis, and Therapies

Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a diverse range of neurological and psychiatric manifestations occurring in patients with systemic lupus erythematosus (SLE); however, these events are ultimately attributed to NPSLE only after rigorous exclusion of alternative etiologies and secondary causes. These manifestations result directly from lupus-related inflammation, vascular damage, or autoantibody effects on the central and peripheral nervous systems. The purpose of this review is to provide an updated overview of NPSLE, the multidisciplinary approach in diagnosing NPSLE, the different proposed mechanisms of pathophysiology, as well as the available treatment options. It also sheds light on the introduced advancements in personalized targeted therapy for NPSLE. A comprehensive review of the relevant literature on the state of NPSLE diagnosis, pathogenesis, and treatment was conducted. Different search databases (PubMed, Google Scholar, ScienceDirect) were searched for studies published, prioritizing the most recent ones. Search terms included "neuropsychiatric manifestations of SLE", "diagnostic biomarkers", "targeted therapy", and "autoantibodies and neurotoxicity". Only English-language articles were included. As a narrative review, the selection was not systematic and may be subject to selection bias. The review presented the most evident recent diagnostic approaches of NPSLE, including those currently in clinical use and those still under investigation. Moreover, the complex pathogenesis of autoantibodies, inflammatory cells, and cytokines, along with other environmental and genetic factors, was discussed. The emerging and promising strategies for NPSLE management targeting proposed or emerging pathogenic pathways offer new opportunities to treat one of the most severe complications of SLE. The growing understanding of the pathogenesis of NPSLE paves the way for targeted therapy and symptom management. Despite promising advances, actual clinical trials are needed to evaluate the efficacy and safety of the proposed treatment strategies. Future research should focus on validating the personalized targeted interventions and ultimately improving prognosis and outcomes for patients suffering from this severe complication of NPSLE.