Treatment of neuropsychiatric systemic lupus erythematosus: clinical challenges and future perspectives.

: Neuropsychiatric (NP) involvement represents an emerging frontier in systemic lupus erythematosus (SLE), posing significant challenges due to its clinical diversity and obscure pathophysiology. The authors herein discuss selected aspects in the management of NPSLE based on existing literature and our experience, aiming to facilitate routine medical care.: Research related to diagnosis, neuroimaging, treatment and outcome is discussed, focusing on data published in PubMed during the last 5 years. Selected translational studies of clinical relevance are included.: Identification of NPSLE patients who may benefit from appropriate treatment can be facilitated by attribution algorithms. Immunosuppressants are typically indicated in recurrent seizures, optic neuritis, myelopathy, psychosis and peripheral nerve disease, although a low threshold is recommended for cerebrovascular disease and other NP manifestations, especially when SLE is active. With the exception of stroke with positive antiphospholipid antibodies, anti-coagulation is rarely indicated in other syndromes. Refractory NPSLE can be treated with rituximab, whereas the role of other biologics remains unknown. Advances in the fields of biomarkers, neuroimaging for brain structural, perfusion or functional abnormalities, and design of novel compounds targeting not only systemic autoimmunity but also inflammatory and regenerative pathways within the nervous system, hold promise for optimizing NPSLE management.