Updated: 6/30/2020

Cryptococcus neoformans

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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
  • Pathogenesis
    • the yeast is inhaled and subsequently disseminated hematogenously to the brain
  • Prognosis
    • without treatment, the infection leads to death
    • with treatment, mortality rate is ~20%
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

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