After Unprotected Sex, 50-Year-Old Has Rash, Severe Weakness

Amber M. Bokhari, MD


August 22, 2022

Diagnostic confirmation of pulmonary cryptococcal infection includes histopathologic examination of suspected lesions, fungal stains and culture, serum and BAL fluid cryptococcal antigen tests, and radiography. Figure 2 shows cryptococcosis in a human lung. If the results of diagnostic tests are positive and the patient is immunocompromised, they must be evaluated for disseminated infection. Dissemination to the CNS is most likely; thus, blood and CSF cultures and cryptococcal antigen testing should be ordered, as in this patient.

The serum cryptococcal antigen test is an excellent screening modality in immunocompromised hosts owing to a high sensitivity of over 70%. False-positive tests can occur with fungal infection with Trichosporon spp or bacterial infection with Stomatococcus or Capnocytophaga. False-negative tests are associated with the prozone effect owing to high antigenemia detected with an agglutination assay without prior treatment with pronase.

Sputum culture is often positive in immunocompromised patients, including those who have a solid organ transplant or HIV infection or who are receiving immune therapy. Performing a bronchoscopy is important in patients with advanced HIV infection to rule out other opportunistic infections, such as PCP, M tuberculosis infection, or MAC infection. A biopsy should be obtained for histopathologic confirmation of the diagnosis as well as to rule out cancer.

In immunocompromised hosts, including patients with advanced HIV/AIDS, chest radiography and other imaging modalities may show abnormalities such as bilateral alveolar lymphadenopathy, mass lesions, alveolar infiltrates, and pleural effusions. It is not unusual to see other opportunistic infections as well.

In patients with disseminated disease, neurologic symptoms, or a compromised immune system, as in the man in this case, LP is required to evaluate for possible cryptococcal meningoencephalitis. If the opening pressure is > 250-cm H2O, serial therapeutic LPs may be necessary to lower the intracranial pressure to < 200-cm H2O. If the intracranial pressure remains elevated, an LP shunt may be placed. Figure 3 shows cryptococcal disease in a human brain at light magnification.

Patients with mild to moderate pulmonary disease with few infiltrates can be treated effectively with oral fluconazole 400 mg or 6 mg/kg for a total duration of 6-12 months. Other azoles such as itraconazole, voriconazole, or posaconazole may be used if fluconazole is contraindicated or unavailable. However, severe pulmonary disease, disseminated cryptococcal infection, or a serum cryptococcal antigen titer ≥ 1:512 can be treated depending on the severity of the infection with IV induction vs an oral regimen.

Meningoencephalitis should be treated with a 2-week induction phase of liposomal amphotericin B 3-4 mg/kg IV every 24 hours plus oral flucytosine 25 mg/kg four times a day. This phase can be prolonged if cultures are not sterilized or the patient's condition fails to improve. The induction is followed by a 10-week consolidation phase with oral fluconazole 400 mg once daily. This phase is followed by maintenance or secondary prophylaxis with oral fluconazole 200 mg once daily until the immune system recovers with HAART in patients with HIV infection or with cessation of immunosuppressive therapy in patients with a solid organ transplant.[3]

Patients with HIV should continue chronic suppressive therapy with fluconazole 200 mg per day. HAART can be deferred until after 5 weeks of treatment to avoid clinical worsening due to immune reconstitution inflammatory syndrome. In patients with HIV infection who are receiving antiretroviral therapy and have a CD4 T-cell count > 100 cells/µL, with a suppressed viral load and a declining cryptococcal antigen titer, maintenance fluconazole can be discontinued after 1 year of treatment. However, no role has been established for monitoring serum cryptococcal antigen titers to determine the duration of therapy, and serial testing is not done.

Localized cryptococcal infections of the lung that are resistant to medical therapy or cryptococcomas in the brain parenchyma that cause mass effects may be surgically removed if necessary. Similarly, skin or joint lesions may be removed if they cause symptoms.