Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 36-06: Cryptococcosis + Key Features Download Section PDF Listen +++ +++ 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 Download Section PDF Listen +++ +++ 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 Download Section PDF Listen +++ +++ 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 for cryptococcal capsular antigen in > 90% Blood cultures also have good yield, especially in HIV-infected patients Antigen testing by a lateral flow assay Has 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 +++ Diagnostic Procedures ++ Given the high propensity of the organism for the CSF, lumbar puncture is mandatory for any patient with disseminated disease Examination of CSF via fungal stain, culture, and antigen tests usually sufficient to establish diagnosis + Treatment Download Section PDF Listen +++ +++ Medications +++ Acute therapy ++ Because of decreased efficacy initial therapy with an azole alone is not recommended for treatment of acute cryptococcal meningitis Induction therapy Liposomal amphotericin B, 3–4 mg/kg/day intravenously for 14 days followed by fluconazole, 400 mg/day orally for an additional 8 weeks is preferred This regimen has been quite effective, achieving clinical responses and CSF sterilization in about 70% of patients Switch from amphotericin B to fluconazole after clinical improvement and conversion of CSF culture to negative Early addition of flucytosine, 100 mg/kg/day orally divided into four equal doses given every 6 hours, improves survival, but toxicity is common Non–AIDS-related cryptococcal meningitis Similar treatment, although mortality is higher Continue therapy until CSF culture is negative +++ Maintenance therapy ++ AIDS-related cryptococcal meningitis: fluconazole, 200 mg orally once daily long-term, after immediate therapy to prevent > 50% relapse rate Secondary prophylaxis can be discontinued after patients have had satisfactory response to antiretroviral therapy (eg, CD4 cell count > 100–200 cells/mcL for at least 6 months) Published guidelines suggest that 6–12 months of fluconazole can be used as maintenance therapy in patients without AIDS following successful treatment of the acute illness +++ Therapeutic Procedures ++ Repeated lumbar punctures or ventricular shunting should be done to relieve high CSF pressures or hydrocephalus + Outcome Download Section PDF Listen +++ +++ Complications ++ Communicating hydrocephalus +++ Prognosis ++ Poor prognosis indicated by Activity of predisposing conditions Older age Organ failure Lack of CSF pleocytosis High initial antigen titer in serum or CSF Decreased mental status Increased intracranial pressure Disease outside CNS Fluconazole maintenance therapy after HIV-related meningitis in patients whose CSF has been sterilized by induction therapy Decreases relapse rate tenfold compared with placebo Decreases relapse rate threefold compared with weekly amphotericin B + References Download Section PDF Listen +++ + +Beardsley J et al. Central nervous system cryptococcal infections in non-HIV infected patients. J Fungi (Basel). 2019 Aug 2;5(3):E71. [PubMed: 31382367] + +Maziarz EK et al. Cryptococcosis. Infect Dis Clin North Am. 2016 Mar;30(1):179–206. [PubMed: 26897067] + +Setianingrum F et al. Pulmonary cryptococcosis: a review of pathobiology and clinical aspects. Med Mycol. 2019 Feb 1;57(2):133–50. [PubMed: 30329097] + +Skipper C et al. Diagnosis and management of central nervous system cryptococcal infections in HIV-infected adults. J Fungi (Basel). 2019 Jul 19;5(3):E65. [PubMed: 31330959]