Snapshot A 62-year-old man presents to the emergency room with headaches, fevers, and generalized malaise for the past week. His latest visit to the HIV clinic reveals a CD4+ cell count of 50. He has had issues with insurance and has not been on his HIV medications. A lumbar puncture is performed and yeast with clear halos is seen with India ink stain. He is started immediately on the appropriate medications. Introduction Classification Cryptococcus neoformans a urease-positive monomorphic encapsulated yeast with 5-10 μm narrow budding transmitted via inhalation found in soil and pigeon droppings clinical syndromes cryptococcosis cryptococcal meningitis cryptococcal encephalitis Epidemiology Risk factors hematologic malignancy immunocompromised status HIV/AIDS patients transplant recipients CD4+ cell count < 100 mm3 occupational exposures to pigeons ETIOLOGY Pathogenesis the yeast is inhaled and subsequently disseminated hematogenously to the brain Presentation Symptoms fever headache generalized malaise may have memory loss or confusion Physical exam may have altered mental status may not have any neck stiffness papilledema in patients with elevated intracranial pressure Imaging Brain computed tomography (CT) or magnetic resonance imaging (MRI) indication all patients findings soap bubble lesions variably enhancing lesions hydrocephalus Studies Labs detection of capsular antigen in serum of cerebrospinal fluid (CSF) latex agglutination test lumbar puncture cell count lymphocytic pleocytosis low glucose elevated total protein culture on Sabouraud agar India ink stain shows yeast with clear halos mucicarmine shows yeast with red inner capsules Making the diagnosis based on clinical presentation and laboratory studies Differential Bacterial meningitis distinguishing factors typically presents more acutely with an acute headache and neck stiffness lumbar puncture will reveal bacterial infection rather than fungal infection Treatment Management approach patients with cryptococcal meningitis are treated with amphotericin B and flucytosine, followed by fluconazole if patients on therapy experience headaches due to increased intracranial pressure, they may receive serial lumbar punctures Medical amphotericin B indications all patients used along with flucytosine for 10-14 days flucytosine indications all patients used along with amphotericin B for 10-14 days fluconazole indications used after treatment with amphotericin B and flucytosine maintenance and suppressive therapy Complications Disseminated disease affecting the skin, bones, joints, and lungs Prognosis Without treatment, the infection leads to death With treatment, mortality rate is ~20%