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Key Features

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Essentials of Diagnosis
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  • 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

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General Considerations
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  • 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

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Clinical Findings

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Symptoms and Signs
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  • 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

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Differential Diagnosis
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  • 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

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Diagnosis

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Laboratory Findings
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  • 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

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Imaging
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  • Radiography

    • Usually shows lower lobe infiltrates or nodular densities

    • Shows effusions less often

    • Rarely shows cavitation, hilar adenopathy, or calcification

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

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Diagnostic Procedures
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  • Lumbar puncture indicated for

    • Immunocompetent patients with cryptococcal antigen in the serum

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

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Treatment

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  • 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 flucytosine

  • After this, fluconazole alone (10 mg/kg/d) is maintained for 8 weeks ...

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