Cryptococcosis

Key Features

Essentials of Diagnosis

• Acute pneumonitis in immunocompetent individuals

• Immunosuppressed patients especially vulnerable to CNS infection (headache, vomiting, cranial nerve palsies, meningeal signs; mononuclear cell pleocytosis)

• Cryptococcal antigen detected in CSF; also in serum and urine in some patients

• Cryptococcus is readily isolated on routine media

General Considerations

• Cryptococcus neoformans is a ubiquitous soil yeast

• It survives best in soil contaminated with bird excrement, especially that of pigeons

• Inhalation is the presumed route of inoculation

• Infections in children are rare, even in heavily immunocompromised patients such as those with HIV infection

• Immunocompetent individuals can be infected, especially by Cryptococcus gattii, which is an emerging pathogen in Canada and the Pacific Northwest

• Asymptomatic carriage does not occur

Clinical Findings

Symptoms and Signs

• Pulmonary disease

  • Frequently asymptomatic

  • Symptoms are nonspecific and subacute

    • Cough

    • Weight loss

    • Fatigue

  • Pulmonary infection precedes dissemination to other organs

  • Pneumonia is the primary manifestation in one-third of patients

  • Cryptococcal pneumonia may coexist with CNS involvement

• Meningitis

  • CNS disease is the primary manifestation in 50% of patients

  • Headache, vomiting, and fever occur over days to months

  • Meningeal signs and papilledema are common

  • Cranial nerve dysfunction and seizures may occur

• Other forms

  • Cutaneous forms

    • Usually secondary to dissemination

    • Papules, pustules, and ulcerating nodules are typical

  • Bones (rarely joints) may be infected

    • Osteolytic areas are seen

    • Process may resemble osteosarcoma

  • Many other organs, especially the eyes, can be involved with dissemination

Differential Diagnosis

• Cryptococcal meningitis may mimic tuberculosis, viral meningoencephalitis, meningitis due to other fungi, or a space-occupying CNS lesion

• Lung infection is difficult to differentiate from many causes of pneumonia

Diagnosis

Laboratory Findings

• Serum, CSF, and urine should be tested

• CSF usually has a lymphocytic pleocytosis; may be completely normal in immunosuppressed patients with meningeal infection

• Direct microscopy may reveal organisms in sputum, CSF, or other specimens

• Latex agglutination or ELISA can detect capsular antigen; both are sensitive (> 90%) and specific

• False-negative CSF tests occur rarely

Imaging

• Radiography

  • Usually shows lower lobe infiltrates or nodular densities

  • Shows effusions less often

  • Rarely shows cavitation, hilar adenopathy, or calcification

• CT or MRI scan may demonstrate single or multiple focal mass lesions (cryptococcoma) in CNS

Diagnostic Procedures

• Lumbar puncture indicated for

  • Immunocompetent patients with cryptococcal antigen in the serum

  • All immunocompromised patients with cryptococcal pulmonary disease to rule out CNS infection

Treatment

• Patients with symptomatic pulmonary disease should receive fluconazole for 3–6 months

• Severely ill patients should receive amphotericin B (0.7 mg/kg/d)

• Meningitis is treated with amphotericin B (increase dose to 1 mg/kg/d) and flucytosine (100 mg/kg/d); fluconazole can be substituted for ...