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Neuropsychiatric systemic lupus erythematosus (NPSLE) has a wide variety of neurologic and psychiatric features. NPSLE symptoms and the psychotic features of primary psychiatric disorders often overlap with each other. These psychotic features often mask and delay the diagnosis of NPSLE. We present the case of a 59-year-old female previously diagnosed with bipolar disorder and generalized anxiety disorder presenting with altered mental status (AMS), subsequently diagnosed with neuropsychiatric lupus.Initially, medication overdose was suspected as an empty bottle of trazodone was found beside her. Obtaining an appropriate history was difficult due to the patient’s altered mental status and absence of family members at bedside. The patient was found to have an elevated gamma gap, and further workup was pursued. Subsequently, positive antinuclear antibody (ANA) and anti-double stranded DNA antibody (anti-dsDNA) was detected. During the hospitalization, she was found to meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE). Lumbar puncture with cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, elevated protein with no bacteria and likely a non-infectious process. Magnetic resonance imaging (MRI) spectroscopy of the brain revealed a reversal of normal Hunter's angle, with elevated choline-to-creatine ratio within the white matter, and a lactate peak, which may be present in neuropsychiatric lupus. The patient was diagnosed with SLE with neuropsychiatric manifestations. Consequently, a kidney biopsy was obtained showing Class IV diffuse proliferative glomerulonephritis with fibrillary component likely related to lupus nephritis. The patient was started on treatment for neuropsychiatric lupus, which includes treatment for lupus nephritis with high dose pulse methylprednisolone. The anti-dsDNA titers decreased from 81 to 15 IU/ml and the patient displayed a gradual improvement in her mental status. She was started on cyclophosphamide while inpatient and discharged with the combination of cyclophosphamide, prednisone, along with rheumatology follow-up.This case stresses the importance of ruling out organic causes of AMS before diagnosing patients with a psychiatric disorder. Not every patient with SLE will meet the criteria for diagnosis at the same point in time; hence, it is important to obtain an appropriate history and physical examination to support such diagnosis. We believe our patient had a neuropsychiatric manifestation of SLE, which demonstrates the importance to keep this diagnosis in the list of differentials when assessing a patient presenting with AMS.

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