cryptococcal meningitis

Cryptococcus neoformans is an encapsulated yeast found in soil contaminated with bird (especially pigeon) droppings; C. gattii is associated with eucalyptus trees and can infect immunocompetent hosts. Infection begins via inhalation into the lungs, often subclinical, followed by hematogenous dissemination to the CNS, particularly in immunosuppressed individuals (HIV/AIDS with CD4 <100, transplant recipients, corticosteroid use). Pathogenesis relies on the polysaccharide capsule, which inhibits phagocytosis and is a key virulence factor; it also produces melanin (via laccase) protecting against oxidative damage, and urease.

Clinical presentation is typically subacute-to-chronic, with headache, low-grade fever, malaise, nausea/vomiting, and altered mental status; classic meningismus (nuchal rigidity, photophobia) may be subtle or absent due to blunted immune response in AIDS patients. Increased intracranial pressure is a hallmark and major cause of morbidity/mortality, requiring serial therapeutic lumbar punctures.

Diagnosis: CSF analysis shows elevated opening pressure, lymphocytic pleocytosis (may be minimal in AIDS), elevated protein, low glucose. India ink stain shows encapsulated yeast with narrow-based budding (classic "halo" sign) but has lower sensitivity than cryptococcal antigen (CrAg) testing, which is both highly sensitive and specific in serum and CSF. Culture remains gold standard for confirmation.

Treatment follows a three-phase approach: induction with liposomal amphotericin B plus flucytosine (2 weeks), consolidation with high-dose fluconazole (8 weeks), and maintenance with lower-dose fluconazole (at least 1 year, until immune reconstitution in HIV patients with ART). Management of elevated ICP via repeated LPs or CSF shunting is critical. In HIV patients, antiretroviral therapy should be delayed 2-5 weeks after starting antifungal treatment to avoid immune reconstitution inflammatory syndrome (IRIS), which can cause paradoxical worsening.

High-yield associations: AIDS-defining illness, soap bubble lesions in basal ganglia on MRI (gelatinous pseudocysts), and mucicarmine stain highlighting the capsule on histopathology.