Abstract
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a rare and poorly understood manifestation of systemic lupus erythematosus, encompassing a wide range of neurological and psychiatric symptoms. In order to highlight the diagnostic complexity and therapeutic challenges of NPSLE, this report presents the management of three distinct presentations. We retrospectively reviewed cases of three female patients with NPSLE admitted to a tertiary care hospital. Clinical presentation, diagnostic workup, treatment strategies, and outcomes were analyzed. Each case demonstrated unique NPSLE manifestations: acute confusional state in the setting of sepsis, cerebral vasculitis with retinal involvement, and catatonia. Treatments included high-dose corticosteroids, cyclophosphamide, and mycophenolate mofetil, with varying degrees of clinical improvement. NPSLE remains a diagnostic challenge due to its heterogeneity and lack of definitive biomarkers. Early recognition and individualized immunosuppressive treatment are essential for improved outcomes.