A 32-year-old woman with known SLE (ANA positive, anti-dsDNA positive, diagnosed 4 years ago) on hydroxychloroquine 400 mg daily and prednisolone 10 mg daily presents with a 2-week history of severe headache, photophobia, and neck stiffness. Cerebrospinal fluid (CSF) analysis shows: protein 120 mg/dL (normal 15–45), glucose 35 mg/dL (serum glucose 95 mg/dL), WBC 85/μL (90% lymphocytes), negative bacterial culture, negative Gram stain, and negative PCR for common viral pathogens. Brain MRI shows no focal lesions. What is the most likely diagnosis?

Explanation

## Clinical Presentation & Differential **Key Point:** This patient presents with meningeal signs (headache, photophobia, neck stiffness) and CSF pleocytosis with negative infectious workup in the setting of known SLE. The combination of: - Lymphocytic pleocytosis (85/μL, 90% lymphocytes) - Elevated protein (120 mg/dL) - Low CSF glucose (35 mg/dL with normal serum glucose = CSF:serum ratio 0.37) - Negative bacterial, fungal, and viral cultures/PCR - Normal brain MRI ...in an SLE patient strongly suggests **lupus meningitis** (CNS-SLE). ## CSF Profile Comparison: Differential Diagnosis | Feature | Lupus Meningitis | TB Meningitis | Viral Meningitis | Drug-Induced Aseptic | |---------|------------------|---------------|------------------|---------------------| | **WBC count** | 50–500/μL (lymphocytic) | 100–500/μL (lymphocytic) | 100–1000/μL (variable) | 10–100/μL | | **Protein** | Elevated (80–200) | Very elevated (200–500) | Mildly elevated (50–100) | Mildly elevated (50–100) | | **Glucose** | Low (often <40% serum) | Very low (<25% serum) | Normal or mildly low | Normal | | **Culture/PCR** | Negative | Positive (AFB, PCR) | Positive (viral PCR) | Negative | | **Gram stain** | Negative | Negative | Negative | Negative | | **Time course** | Subacute (days–weeks) | Subacute–chronic (weeks) | Acute (days) | Acute (days–weeks) | **High-Yield:** Lupus meningitis is the most common form of CNS-SLE. It typically presents with: - Meningeal irritation signs - Lymphocytic pleocytosis - Elevated protein - Low-normal or low glucose - **Negative infectious workup** (this is the key discriminator) ## CNS-SLE Manifestations Spectrum ```mermaid flowchart TD A[SLE with CNS symptoms]:::outcome --> B{Type of CNS involvement?}:::decision B -->|Meningitis| C[Lupus meningitis]:::outcome B -->|Seizures| D[Cerebritis/vasculitis]:::outcome B -->|Stroke| E[Thrombosis/vasculitis]:::outcome B -->|Psychosis| F[Diffuse CNS-SLE]:::outcome B -->|Myelopathy| G[Transverse myelitis]:::outcome C --> H[CSF: lymphocytic pleocytosis, elevated protein, low glucose]:::action H --> I[Exclude infection, then treat with corticosteroids ± immunosuppression]:::action ``` **Clinical Pearl:** The CSF glucose of 35 mg/dL with serum glucose 95 mg/dL gives a CSF:serum ratio of 0.37 — this is consistent with lupus meningitis. While TB meningitis also causes low CSF glucose, the absence of any clinical risk factors for TB (no cough, no constitutional symptoms mentioned) and negative AFB/culture make TB less likely. Viral meningitis typically has normal or mildly low CSF glucose. **Mnemonic for CNS-SLE:** **VASCULITIS** — Vasculitis, Antibodies (antiribosomal P, anti-NMDA), Seizures, Cognitive dysfunction, Ischemic stroke, Lupus meningitis, Intracranial hypertension, Transverse myelitis, Intracerebral hemorrhage, Syndrome of inappropriate ADH. ## Why This Is Lupus Meningitis 1. **Known SLE** with positive serology (ANA, anti-dsDNA) — established diagnosis. 2. **Negative infectious workup** — rules out bacterial, TB, and common viral causes. 3. **CSF profile** — lymphocytic pleocytosis with elevated protein and low glucose is classic for lupus meningitis. 4. **Normal MRI** — excludes focal lesions, infarction, or hemorrhage; supports diffuse meningeal inflammation. 5. **Clinical context** — on hydroxychloroquine and prednisolone, suggesting disease activity despite treatment. **Warning:** Do not assume all meningitis in SLE patients is lupus meningitis — always exclude infection first, especially TB and cryptococcal meningitis in immunocompromised patients.