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

Key Features

Essentials of Diagnosis

  • Predisposing factors

    • Chemotherapy for hematologic malignancies

    • Hodgkin disease

    • Corticosteroid therapy

    • Structural lung diseases

    • AIDS

    • Transplant recipients

    • TNF-alpha inhibitor therapy

  • Most common cause of fungal meningitis

  • Symptoms of headache, abnormal mental status; meningismus seen occasionally, though rarely in patients with AIDS

  • 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 and is especially problematic in immunocompromised patients

  • C neoformans variety gattii causes localized infections (cryptococcomas) in tropical climates and has close association with eucalyptus plants

  • C neoformans has a special predilection for the CNS and is the most common fungal cause of meningitis

  • 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

    • Cellular immunodeficiency, including underlying hematologic malignancies under treatment

    • Hodgkin disease

    • Long-term corticosteroid therapy

    • Solid-organ transplant

    • 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 in about 50%, but uncommon in patients with AIDS

  • 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

  • The immune reconstitution inflammatory syndrome (IRIS), which is paradoxical clinical worsening associated with improved immunologic status, has been reported in HIV-positive and transplant patients with cryptococcosis as well as non-AIDS patients being treated for C gattii infection

Differential Diagnosis

  • Histoplasmosis

  • Coccidioidomycosis

  • Tuberculous meningitis

  • Neurosyphilis

  • Acanthamoeba (amebic encephalitis)

  • Toxoplasmosis

  • Lyme meningitis


Laboratory Tests

  • In HIV-infected patients with cryptococcosis, serum cryptococcal antigen positive in 95%

  • In patients with cryptococcal meningitis, CSF shows

    • Increased opening pressure

    • Variable pleocytosis

    • Increased protein

    • Decreased glucose

    • Budding encapsulated fungi

  • Up to 50% ...

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