Acute Psychosis as the Sole Initial Manifestation of Systemic Lupus Erythematosus: A Diagnostic Challenge

Neuropsychiatric systemic lupus erythematosus (NPSLE) represents one of the most complex and heterogeneous manifestations of systemic lupus erythematosus (SLE). Psychosis is an uncommon but severe feature of NPSLE and usually occurs in the setting of established multisystem disease. Acute psychotic presentation as the sole initial manifestation of SLE is exceptionally rare and poses considerable diagnostic challenges. We report the case of a 24-year-old woman with no prior psychiatric or medical history who developed abrupt-onset psychosis characterized by insomnia, aggression, persecutory delusions, and auditory hallucinations. Initial evaluation suggested first-episode psychosis; however, poor response to antipsychotic therapy and the presence of unexplained pancytopenia with elevated inflammatory markers prompted further investigation. Autoimmune testing revealed high-titer antinuclear antibodies, elevated anti-double-stranded DNA, anti-Smith, and anti-ribosomal P antibodies, hypocomplementemia, and a positive direct Coombs test. Infectious, metabolic, toxic, and structural neurological causes were systematically excluded. The patient fulfilled the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for SLE and met diagnostic attribution for lupus psychosis. Treatment with high-dose pulse intravenous methylprednisolone and intravenous cyclophosphamide resulted in rapid and sustained resolution of psychotic symptoms, with normalization of laboratory abnormalities. Acute psychosis may rarely be the first and isolated manifestation of SLE. This case highlights the importance of considering NPSLE in young patients presenting with first-episode psychosis and underscores the role of early immunosuppressive therapy in achieving favorable outcomes, even in resource-limited settings.