What is the diagnosis and treatment for a patient with lymphocytic pleocytosis, elevated proteins, and a positive Indian ink test in the cerebrospinal fluid?

Cryptococcal Meningitis: Diagnosis and Treatment

Diagnosis

The combination of lymphocytic pleocytosis, elevated CSF protein, and positive Indian ink stain is diagnostic of cryptococcal meningitis, most commonly caused by Cryptococcus neoformans in HIV-infected and immunocompromised patients. 1

Key Diagnostic Features

• CSF analysis typically reveals:

  • Mildly elevated protein (often >100 mg/dL) 1
  • Glucose ranging from low to normal 1
  • Pleocytosis consisting mostly of lymphocytes, though some patients may have minimal or no cells 1
  • Positive India ink stain demonstrating numerous yeasts 1
  • Opening pressure usually elevated, with pressures >200 mm H2O occurring in up to 75% of patients 1

• Serum cryptococcal antigen is almost always positive in cases of CNS disease and serves as a useful initial screening tool 1

• CSF cryptococcal antigen is detected at high titer in virtually all patients with meningitis or meningoencephalitis 1

• Blood cultures are positive for C. neoformans in up to 75% of patients with HIV-associated cryptococcal meningitis 1

Critical Clinical Context

• The majority of cases occur in patients with CD4+ counts <50 cells/µL 1

• Clinical presentation is typically subacute meningitis or meningoencephalitis with fever, malaise, and headache 1

• Classic meningeal signs (neck stiffness, photophobia) occur in only one-fourth to one-third of patients 1

• Elevated intracranial pressure occurs in >50% of patients and is an important contributor to morbidity and mortality 1

Important Diagnostic Pitfall

Pleocytosis in CSF of any immunosuppressed patient should raise suspicion of cryptococcal meningitis, as immunocompromised patients can present with varied CSF findings including significant inflammatory cell counts 2. The presence of lymphocytic pleocytosis does not exclude cryptococcal infection, even though minimal inflammation is more typical 1.

Treatment

Initial Antifungal Therapy

For HIV-infected patients with cryptococcal meningitis, combination therapy with amphotericin B and flucytosine is the standard initial treatment. 1, 3

• Duration of initial therapy: 10-12 weeks after CSF becomes culture negative 1, 4

• Four-week regimen should be reserved only for patients meeting ALL of the following criteria: 3

  • Meningitis without neurologic complications
  • No underlying disease or immunosuppressive therapy
  • Pretreatment CSF white-cell count >20 cells/mm³
  • Serum cryptococcal antigen titer <1:32
  • At 4 weeks: negative CSF India ink preparation and serum/CSF cryptococcal antigen titers <1:8

• Patients not meeting these criteria require at least 6 weeks of therapy 3

Consolidation and Maintenance Therapy

• After initial therapy, fluconazole 400 mg once daily may be used based on patient response 4

• For suppression of relapse in AIDS patients: fluconazole 200 mg once daily 1, 4

Management of Elevated Intracranial Pressure

Aggressive management of elevated intracranial pressure is critical and directly impacts survival. 1, 5

Assessment and Intervention Protocol:

• Before lumbar puncture: If focal neurological signs or obtunded state present, obtain brain imaging to rule out mass lesions 1

• If opening pressure ≥250 mm H2O: Perform lumbar drainage sufficient to achieve closing pressure <200 mm H2O or 50% of initial opening pressure 1

• If elevated pressure persists: Consider lumbar drain or ventriculoperitoneal shunt 1

• Corticosteroids are NOT recommended for HIV-infected patients, and evidence of benefit for HIV-negative patients is not established 1

• Follow-up lumbar puncture at 2 weeks to reassess pressure 1

• Patients whose CSF pressure increased between baseline and week 2 had poorer clinical response, emphasizing the importance of pressure management 1, 5

Prognostic Factors

Three pretreatment factors predict favorable response: 3

• Headache as a symptom
• Normal mental status
• CSF white-cell count >20 cells/mm³

Patients with highest baseline opening pressures (≥250 mm H2O) are distinguished by: 5

• Higher CSF cryptococcal antigen titers
• More frequently positive India ink smears
• More frequent neurological complications (headache, meningismus, papilledema, hearing loss, pathological reflexes)

Patients with pretreatment opening pressure <250 mm H2O have increased short-term survival compared to those with higher pressures 5

Pediatric Dosing

• Acute cryptococcal meningitis: 12 mg/kg on first day, then 6 mg/kg once daily (may use 12 mg/kg once daily based on response) 4

• Suppression of relapse in children with AIDS: 6 mg/kg once daily 4