Could the meningitis be aseptic or a manifestation of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)?

Aseptic Meningitis as a Manifestation of NPSLE

Yes, aseptic meningitis can be a manifestation of NPSLE, though it is rare (occurring in <1% of SLE patients), and you must aggressively exclude infectious causes before attributing it to lupus. 1

Epidemiology and Clinical Context

• Aseptic meningitis is classified as a rare NPSLE manifestation with a cumulative incidence of less than 1%, making it one of the least common neuropsychiatric presentations of SLE 1
• NPSLE manifestations commonly occur within the first year after SLE diagnosis (50-60% of cases) and frequently present alongside generalized disease activity (40-50% of cases) 1
• Aseptic meningitis in SLE may appear as an early manifestation that can herald more serious brain damage, and historical case series suggest it may precede other neuropsychiatric complications 2

Critical Diagnostic Approach

The EULAR guidelines emphasize that lumbar puncture with CSF analysis and MRI should be performed to exclude non-SLE causes, especially infection 1

Essential workup includes:

• Lumbar puncture with comprehensive CSF analysis: cell count, protein, glucose, Gram stain, culture, and PCR for HSV and other viruses as clinically indicated 1
• MRI of brain using the recommended protocol: conventional sequences (T1/T2, FLAIR), diffusion-weighted imaging, and gadolinium-enhanced T1 sequences 1
• Mild-to-moderate CSF abnormalities are common (40-50%) in NPSLE but are non-specific 1

Key clinical red flags requiring immediate infectious workup:

• Fever or concomitant infection
• Immunosuppression status
• Presence of antiphospholipid antibodies
• Use of anticoagulants
• Focal neurological signs
• Altered mental status
• Meningismus
• Generalized SLE activity 1

Important Differential Considerations

Before diagnosing lupus-related aseptic meningitis, you must exclude:

• Infectious meningitis (bacterial, viral, fungal) - this is the priority 1
• Drug-induced aseptic meningitis from NSAIDs, azathioprine, or trimethoprim-sulfamethoxazole 3
• Sinus thrombosis, particularly in patients with antiphospholipid antibodies 1
• Cerebral or subarachnoid hemorrhage 1

Treatment When Confirmed as NPSLE

Glucocorticoids and immunosuppressive therapy are indicated for aseptic meningitis when it reflects an immune/inflammatory process, following exclusion of non-SLE-related causes 1

• High-dose glucocorticoids are the first-line treatment 1
• Immunosuppressive agents may be added in severe cases 1
• The combination typically shows good response rates (60-80%) in inflammatory NPSLE manifestations 1

Special Clinical Scenarios:

• Recurrent benign lymphocytic aseptic meningitis (Mollaret-type) has been documented in SLE patients with self-limited episodes and no neurologic sequelae 3
• Some patients may experience chronic meningitis rather than acute episodes 2
• Blood biomarkers (neurofilament light and GFAP) are elevated in active major NPSLE and may decrease after immunotherapy, though this is investigational 4

Critical Pitfall to Avoid

The most dangerous error is attributing meningitis to lupus without adequately excluding infection, especially in immunosuppressed patients. The EULAR guidelines give this a 9.6 agreement score, emphasizing its critical importance 1. Always obtain CSF studies including cultures and viral PCR before initiating immunosuppressive therapy, though empiric antimicrobial coverage may be warranted while awaiting results in high-risk scenarios 1.