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

Demographics

• 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

Diagnosis

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% of AIDS patients have no CSF pleocytosis

• CSF positive ...