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For further information, see CMDT Part 36-06: Cryptococcosis

Key Features

Essentials of Diagnosis

  • Most common cause of fungal meningitis

  • Predisposing factors

    • Chemotherapy for hematologic malignancies

    • Hodgkin disease

    • Corticosteroid therapy

    • HIV infection

    • Transplant recipients

    • TNF-α inhibitor therapy

  • Headache, abnormal mental status; meningismus seen occasionally, though rarely in HIV-infected patients

  • Demonstration of capsular polysaccharide antigen in cerebrospinal fluid (CSF) diagnostic

General Considerations

  • Infection is due to

    • Cryptococcus neoformans, an encapsulated budding yeast that is found worldwide in soil and in dried bird droppings

    • Cryptococcus gattii is a closely related species that also causes disease in humans, although it may affect more ostensibly immunocompetent persons

  • C neoformans

    • Accounts for majority of disease worldwide

    • Especially problematic in immunocompromised patients

    • Has a special predilection for the CNS

    • Most common fungal cause of meningitis

  • C neoformans variety gattii

    • Causes localized infections (cryptococcomas) in tropical climates

    • Has close association with eucalyptus plants

  • The polysaccharide capsule is a major virulence factor and provides the basis for antigen testing that is widely available and quite useful in establishing the diagnosis

  • Infection is acquired through inhalation of the organisms into the lungs where infection may remain localized, heal, or disseminate

  • Progressive pulmonary disease can occur in either HIV-infected or noninfected patients in the absence of dissemination

  • Disseminated disease in immunocompetent patients can be especially recalcitrant to therapy


  • Symptomatic cryptococcal pneumonia rarely develops in immunocompetent patients but can occur

  • Progressive lung disease and dissemination usually occur in

    • Malignancies under treatment

    • Hodgkin disease

    • Long-term corticosteroid therapy

    • Solid-organ transplant

    • TNF-α inhibitor therapy

    • HIV infection

Clinical Findings

Symptoms and Signs

  • Disseminated cryptococcosis

    • Most commonly manifests as meningitis, which usually begins with headache, then confusion

    • Cranial nerve abnormalities, nausea, and vomiting may occur

  • Nuchal rigidity and meningeal signs

    • Present in about 50% of patients

    • Uncommon in HIV-infected patients

  • C gattii infection frequently presents with respiratory symptoms along with neurologic signs caused by space-occupying lesions in the CNS

  • Primary C neoformans infection of the skin may mimic bacterial cellulitis, especially in persons receiving immunosuppressive therapy such as corticosteroids

  • Immune reconstitution inflammatory syndrome (IRIS)

    • Is the paradoxical clinical worsening associated with improved immunologic status

    • Can occur in HIV-positive and transplant patients with cryptococcosis, as well as non-AIDS patients being treated for C gattii infection


Laboratory Tests

  • Serum cryptococcal antigen: positive in 95% of HIV-infected patients with cryptococcosis

  • Blood cultures also have good yield, especially in HIV-infected patients

  • Antigen testing by a lateral flow assay

    • Appears to have improved sensitivity and specificity over the conventional latex agglutination test

    • Can provide more rapid diagnostic results

Imaging Studies

  • MRI is more sensitive than CT in finding CNS abnormalities, such as cryptococcomas


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