A 32-year-old woman with established SLE (diagnosed 2 years ago, currently on hydroxychloroquine and low-dose prednisolone) presents with acute onset of severe headache, confusion, and photophobia over 24 hours. Temperature is 38.2°C. On neurological examination, she has neck stiffness and a positive Kernig sign. CSF analysis shows: protein 120 mg/dL, glucose 45 mg/dL (serum glucose 100 mg/dL), WBC 180/μL (90% lymphocytes), Gram stain and bacterial culture negative. Brain MRI shows no focal lesions. Which of the following is the most likely diagnosis?

Explanation

## Diagnosis: Aseptic Meningitis Due to SLE ### Clinical Context This patient has established SLE and presents with acute meningeal signs (headache, neck stiffness, Kernig sign, photophobia) and fever. The key diagnostic clue is the **negative bacterial culture and Gram stain** with a **lymphocytic CSF pleocytosis**—this rules out bacterial meningitis and points toward aseptic meningitis. ### CSF Profile Analysis | Parameter | Finding | Interpretation | |-----------|---------|----------------| | Protein | 120 mg/dL | Mildly elevated (normal <45) | | Glucose | 45 mg/dL | Low (CSF:serum ratio ~0.45) | | WBC count | 180/μL | Pleocytosis | | Cell type | 90% lymphocytes | Viral or autoimmune pattern | | Gram stain | Negative | Rules out bacterial infection | | Bacterial culture | Negative | Rules out bacterial infection | **Key Point:** The combination of negative cultures, lymphocytic pleocytosis, and low CSF glucose in an SLE patient is classic for lupus-associated aseptic meningitis. ### Why This Is Aseptic Meningitis (SLE-Related) **High-Yield:** SLE can cause CNS inflammation through: 1. Direct immune complex deposition in meninges 2. Antineuronal antibodies (anti-NMDA, anti-ribosomal P) 3. Complement activation and vasculitis Lupus meningitis occurs in 1–5% of SLE patients and is a recognized manifestation of CNS lupus (neuropsychiatric lupus, NPSLE). **Clinical Pearl:** The presence of established SLE, negative infectious workup, and lymphocytic CSF with low glucose strongly favors lupus meningitis over infectious causes. ### Differential Diagnosis Exclusion **Bacterial Meningitis:** - Gram stain and culture are **negative** - Bacterial meningitis typically shows higher protein (>200 mg/dL), very low glucose (<40 mg/dL), and predominantly polymorphonuclear pleocytosis - The patient is on hydroxychloroquine and prednisolone (some immune suppression), but negative cultures exclude bacterial infection **Tuberculous Meningitis:** - TB meningitis presents with subacute course (days to weeks), not acute (24 hours) - CSF glucose is typically very low (<20 mg/dL) with very high protein (>500 mg/dL) - No mention of TB risk factors, pulmonary symptoms, or imaging findings suggestive of TB - AFB smear and TB culture would be sent and would be positive in TB meningitis **Viral Meningitis (Enterovirus):** - Viral meningitis typically has **normal or slightly elevated glucose** (CSF:serum ratio >0.4) - This patient has **low CSF glucose** (ratio ~0.45, borderline low), which is atypical for simple viral meningitis - Viral meningitis in an SLE patient is less likely given the established diagnosis and the pattern of CSF findings **Mnemonic for CSF findings in meningitis:** **"VIBE"** - **V**iral: Normal glucose, lymphocytes, negative culture - **I**nflammatory (autoimmune/SLE): Low glucose, lymphocytes, negative culture, **high protein** - **B**acterial: Low glucose, PMNs, **positive culture/Gram stain** - **E**ncephalitis: Variable CSF, but normal glucose more common ### Management Implication Aseptic meningitis in SLE is treated with **increased corticosteroids** (not antibiotics), and consideration of IV methylprednisolone or additional immunosuppression (cyclophosphamide, mycophenolate) depending on severity.