A Case Report on an Infectious–Inflammatory Diagnostic Dilemma: Listeria Meningitis and Suspected Lupus Cerebritis

Background and Clinical Significance: Listeria monocytogenes meningitis is an uncommon cause of bacterial meningitis, with a mortality rate close to 15%, particularly in immunocompromised patients. A concurrent presentation with neuropsychiatric systemic lupus erythematosus (SLE), including lupus cerebritis, poses a significant diagnostic and therapeutic challenge because treatment strategies are inherently conflicting, requiring both aggressive immunosuppression and prompt antimicrobial therapy. We report a rare case of Listeria meningitis with potential lupus cerebritis in a young woman with recently diagnosed discoid lupus receiving corticosteroid therapy. Case Presentation: A 35-year-old woman with SSA/B-positive discoid lupus on a prednisone taper presented with fever, headache, progressive confusion, and encephalopathy. A cerebrospinal fluid analysis demonstrated marked pleocytosis and elevated protein levels, while blood and CSF cultures grew Listeria monocytogenes. Despite the initiation of targeted ampicillin and gentamicin therapy, a concern for active lupus cerebritis based on serologic testing (high-titer ANA 1:640 speckled with positive anti-Smith, RNP, and chromatin antibodies) and neuroimaging prompted treatment with high-dose corticosteroids and plasmapheresis. Serial magnetic resonance imaging revealed multifocal diffusion-restricting lesions and a progressively enlarging ring-enhancing midbrain abscess, findings attributable to both infectious and autoimmune etiologies. Her hospital course was complicated by persistent encephalopathy, autonomic instability, prolonged mechanical ventilation, and the need for tracheostomy and gastrostomy placement. Following prolonged antimicrobial therapy, preventative immunosuppression, and rehabilitation, she demonstrated substantial neurologic recovery with a near-complete return of cognition at the 30-day follow-up. Conclusions: This case highlights the diagnostic complexity and management challenges of uncertainty regarding bacterial meningitis, non-infectious cerebritis, or their potential coexistence. Overlapping clinical and radiographic findings can delay diagnosis and complicate treatment decisions, particularly when immunosuppression required for autoimmune disease may worsen the active infection. Clinicians should maintain a high level of suspicion for multiple concurrent pathologies in immunocompromised patients presenting with encephalopathy, emphasizing the importance of the comprehensive evaluation and timely initiation of either antimicrobial or immunomodulatory therapies.