# Diagnostic Challenges in a Patient With Systemic Lupus Erythematosus (SLE) and Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis: A Case Report

## TL;DR

This case report highlights the difficulty in diagnosing a rare overlap of systemic lupus erythematosus and anti-NMDA receptor encephalitis, emphasizing the need for early recognition to improve treatment outcomes.

## Contribution

The paper presents a rare case of coexisting SLE and NMDAR-E, contributing to the limited literature on this overlapping autoimmune condition.

## Key findings

- The patient's neuropsychiatric symptoms were initially attributed to NPSLE but were later confirmed as NMDAR-E via anti-GluN1 antibodies in CSF.
- Treatment with intravenous immunoglobulin and plasmapheresis led to clinical improvement in the patient.
- The case underscores the importance of considering autoimmune encephalitis in SLE patients with refractory neuropsychiatric symptoms.

## Abstract

Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is an autoimmune disorder characterized by psychiatric and neurological symptoms associated with the presence of anti-GluN1 antibodies in the cerebrospinal fluid (CSF). Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses 19 syndromes and remains a diagnostic challenge due to its heterogeneous clinical presentation and reliance on exclusion. While anti-GluN2 antibodies have been linked to systemic lupus erythematosus (SLE), the coexistence of NPSLE and NMDAR-E has been scarcely reported. Since the first case published in 2016, fewer than 15 patients have been documented worldwide, mostly as isolated case reports and only a few small series including patients with systemic autoimmune diseases such as SLE.

We report a 31-year-old woman with a one-year history of SLE who developed neuropsychiatric manifestations initially attributed to NPSLE. Despite treatment with high-dose corticosteroids, cyclophosphamide, and antipsychotics, she experienced recurrent psychotic episodes with poor response. Brain magnetic resonance imaging (MRI) showed nonspecific hyperintense lesions, and CSF analysis revealed positive anti-GluN1 antibodies, confirming the diagnosis of NMDAR-E. The patient improved after intravenous immunoglobulin and plasmapheresis, and she remained stable under maintenance therapy with azathioprine and rituximab.

This case illustrates the diagnostic complexity of neuropsychiatric manifestations in SLE, where overlapping autoimmunity may conceal the presence of NMDAR-E. Clinicians should maintain a high index of suspicion for autoimmune encephalitis in SLE patients with refractory neuropsychiatric symptoms, as timely recognition and treatment can significantly improve outcomes.