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Updated: Jun 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
  • 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%
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