What are the next steps for a patient with a history of Systemic Lupus Erythematosus (SLE) who presents with a new onset of right-sided dull headache followed by vomiting?

Immediate Comprehensive Workup Required for High-Risk Neuropsychiatric Lupus

This patient requires urgent brain MRI with gadolinium and diffusion-weighted imaging, plus lumbar puncture with CSF analysis to exclude life-threatening causes before attributing symptoms to lupus itself. 1, 2

Why This Is High-Risk and Demands Immediate Action

The combination of new-onset headache with vomiting in an SLE patient represents a high-risk feature that mandates comprehensive evaluation beyond standard headache assessment. 1, 2 The most dangerous clinical error is attributing these symptoms to lupus without adequately excluding infection, stroke, hemorrhage, or cerebral venous sinus thrombosis—particularly critical given that 50-60% of neuropsychiatric manifestations occur within the first year of SLE diagnosis. 3, 1

Urgent Diagnostic Algorithm

First-Line Imaging (Perform Immediately)

• Brain MRI with specific sequences: T1/T2, FLAIR, diffusion-weighted imaging (DWI), and gadolinium-enhanced T1 sequences 3, 4
• This protocol excludes stroke, hemorrhage, cerebral venous sinus thrombosis, and inflammatory lesions 1, 4
• MRI has modest sensitivity (50-70%) for lupus-related manifestations but is essential for excluding dangerous mimics 3

Lumbar Puncture with Comprehensive CSF Analysis

• Mandatory studies: cell count, protein, glucose, Gram stain, culture, and viral PCR (HSV, JC virus if clinically indicated) 3, 1, 2
• This is critical because the most dangerous pitfall is missing CNS infection in an immunosuppressed patient 1, 2
• The European League Against Rheumatism emphasizes this with a consensus score of 9.6 out of 10 2

Additional Laboratory Testing

• Antiphospholipid antibodies (anticardiolipin, anti-β2GPI IgG/IgM, lupus anticoagulant) 3, 5
• Anti-β2GPI antibodies specifically are independently associated with headaches (OR=5.6) and ischemic stroke in SLE patients 5
• Complement levels (C3, C4) and anti-dsDNA antibodies for disease activity assessment 4

Critical Differential Diagnoses to Exclude

Life-Threatening Causes (Must Rule Out First)

• Infectious meningitis: Higher risk in immunosuppressed patients; requires immediate antimicrobial therapy while awaiting confirmatory studies 3, 1
• Cerebral venous sinus thrombosis: Can present with headache and vomiting; requires immediate anticoagulation 1, 6
• Ischemic or hemorrhagic stroke: Common in SLE (cumulative incidence 5-15%); atherosclerotic/thrombotic stroke is far more common than vasculitic stroke 3
• Subarachnoid hemorrhage: Must be excluded with imaging 2

SLE-Related Causes (Diagnose After Exclusions)

• Aseptic meningitis: Very rare (<1% cumulative incidence) but possible 3, 1, 2
• Acute confusional state: Relatively uncommon (1-5% incidence) but requires immunosuppressive therapy if confirmed 3
• Cerebrovascular disease related to antiphospholipid antibodies: Strong risk factor (fivefold increase) 3

Treatment Approach Based on Findings

If Infection Is Excluded and Inflammatory NPSLE Confirmed

• Pulse intravenous methylprednisolone combined with cyclophosphamide is the recommended regimen for severe NPSLE, with response rates of 60-75% 1, 4
• Clinical improvement should occur within days to 3 weeks 1, 4
• Maintenance therapy with azathioprine follows initial treatment 3, 1

If Antiphospholipid Antibodies Are Present

• Antiplatelet and/or anticoagulation therapy is indicated, especially if thrombotic mechanism is identified 3, 1, 4
• Long-term anticoagulation should be considered if stroke occurs in a patient meeting antiphospholipid syndrome criteria 3

Symptomatic Management

• Antiemetics for vomiting 3
• Treatment of aggravating factors including hypertension and metabolic abnormalities 3

Critical Timing Considerations

Delayed treatment initiation beyond 2 weeks is associated with severe neurological deficits, making urgent evaluation and prompt therapy essential. 1, 4 In 65% of cases, neuropsychiatric manifestations precede or occur at SLE diagnosis, meaning this could represent the initial presentation of major organ involvement. 1, 5

Common Pitfall to Avoid

Never assume this is "just a lupus headache"—there is no evidence that headache is more frequent or has unique characteristics in SLE compared to the general population. 1, 2 The presence of vomiting elevates this from a benign primary headache to a high-risk presentation requiring full workup. 1