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  • Most common cause of fungal meningitis.

  • Predisposing factors: chemotherapy for hematologic malignancies, Hodgkin lymphoma, corticosteroid therapy, structural lung diseases, transplant recipients, TNF-alpha inhibitor therapy, and AIDS.

  • Headache, abnormal mental status; meningismus seen occasionally, though rarely in patients with AIDS.

  • Demonstration of capsular polysaccharide antigen or positive culture in CSF is diagnostic.


Cryptococcosis is mainly caused by Cryptococcus neoformans, an encapsulated budding yeast that has been found worldwide in soil and on dried pigeon dung. Cryptococcus gattii is a closely related species that also causes disease in humans, although C gattii may affect more ostensibly immunocompetent persons. It is a major cause of cryptococcosis in the Pacific northwestern region of the United States and may result in more severe disease than C neoformans.

Infections are acquired by inhalation. In the lung, the infection may remain localized, heal, or disseminate. Clinically apparent cryptococcal pneumonia rarely develops in immunocompetent persons. Progressive lung disease and dissemination most often occur in the setting of cellular immunodeficiency, including hematologic malignancies under treatment, Hodgkin lymphoma, long-term corticosteroid therapy, solid-organ transplant, TNF-alpha inhibitor therapy, or HIV infection.


A. Symptoms and Signs

Pulmonary disease ranges from simple nodules to widespread infiltrates leading to respiratory failure. Disseminated disease may involve any organ, but CNS disease predominates. Headache is usually the first symptom of meningitis. Confusion and other mental status changes as well as cranial nerve abnormalities, nausea, and vomiting may be seen as the disease progresses. Nuchal rigidity and meningeal signs occur about 50% of the time but are uncommon in patients with AIDS. This is due to the impaired CNS inflammatory response. Communicating hydrocephalus may complicate the course. 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, can occur in HIV-positive and transplant patients with cryptococcosis, as well as non-AIDS patients being treated for C gattii infection.

B. Laboratory Findings

Respiratory tract disease is diagnosed by culture of respiratory secretions or pleural fluid. For suspected meningeal disease, lumbar puncture is the preferred diagnostic procedure. Spinal fluid findings include increased opening pressure, variable pleocytosis, increased protein, and decreased glucose, though as many as 50% of AIDS patients have no pleocytosis. Gram stain of the CSF usually reveals budding, encapsulated fungi. In patients with AIDS, the serum cryptococcal antigen is a sensitive screening test for meningitis, being positive in over 95% of cases. Cryptococcal capsular antigen in CSF and culture together establish the diagnosis over 90% of the time. Antigen testing by lateral flow assay has improved sensitivity and specificity over ...

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