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

Demographics

• 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

Diagnosis

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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