• Cryptococcus neoformans, a yeastlike fungus

• Cellular immunity is the key defense against infection with Cryptococcus.
• Pulmonary involvement may be either focal or widespread.
• Meningeal involvement with Cryptococcus results from hematogenous spread through the lungs. It can get direct spread from the meninges into the parenchyma of the brain.
• Local reactions can lead to granulomatous formations, which can be seen in both the meninges and the lung.

• Some association exists with exposure to pigeon droppings, although many individuals who are diagnosed with Cryptococcus do not remember a direct exposure.
• Increased risk of cryptococcal infection exists in individuals with a compromised cellular immune system, although it is seen less commonly in young children infected with HIV as compared with adolescents and adults with HIV. There is no person-to-person spread of the infection, with most infections thought to be acquired through aerolization from either contaminated pigeon droppings or contaminated soil.

• Meningeal involvement is one of the most common clinical manifestations of the disease. Meningitis can present with any of the following: fever, headache, malaise, and, at times, photophobia and meningismus. Patients may demonstrate changes in personality and may have papilledema, retinal exudates, decreased hearing, or a facial nerve palsy.
• Cutaneous involvement presents as acneiform lesions that ulcerate and may result from hematogenous spread of the organism or from direct extension from an infected bone. Pulmonary involvement may be asymptomatic and determined at autopsy in up to 50% of cases. It may manifest as cough with a small amount of sputum production, with small amounts of hemoptysis.
• Bone involvement presents with pain and swelling, with a radiographic picture very similar to that for osteogenic sarcoma and requiring biopsy to confirm the diagnosis.

• Prognosis is good with treatment with amphotericin B. However, there is some risk for residual neurologic deficits in up to 40% of patients.
• Left untreated, however, cryptococcal meningitis is fatal. Individuals with impaired cellular immunity, especially those infected with HIV, are at great risk for relapse after initial treatment, with up to 65% experiencing recurrence of infection. Thus, long-term maintenance therapy with fluconazole is recommended.

• Cryptococcal infection is the most common cause of fungal meningitis in the United States and is a particular problem in immunocompromised hosts, especially those with HIV. Cryptococcal meningitis can manifest as headache, nausea and vomiting, fever, and general malaise, with only 30% presenting as meningismus. It is uncommon to see focal neurologic disease, although individuals can present with changes in personality, confusion, disorientation, ataxia, or lethargy.
• Pulmonary Cryptococcus may be asymptomatic but can be manifest with a cough that is productive of small amounts of mucus. Pleural effusions can be found associated with pleuritic-type chest pain.
• Cutaneous involvement can mimic acne-type eruptions, which can ulcerate. Cryptococcus of the bone manifests as pain and swelling, with diagnosis made by biopsy.

• Cryptococcal meningitis should be in the differential diagnosis of any aseptic meningitis, especially in individuals with chronic or recurrent episodes.
• It should be included in any individual with an underlying immunodeficiency who presents with headache, lethargy, fever, or changes in personality.
• Viral encephalitis
• Tuberculous meningitis
• Neoplasia
• Cryptococcus should be considered in the differential diagnosis of chronic cough with or without hemoptysis or in individuals with an isolated pulmonary nodule.

• Cryptococcal meningitis may present as either an indolent infection or as an acute illness.
• In patients infected with HIV, up to 90% will complain of headache and fever.
• Although not common, focal neurologic symptoms can result from cryptococcal meningitis, including decreased hearing, facial nerve palsy, and diplopia.
• Pulmonary disease may be asymptomatic in up to 50% of people infected, or it may present as cough and hemoptysis.

• CSF should be obtained to confirm the diagnosis; it should be sent for cell count and differential; protein; glucose; cultures for bacterial, fungal, and viral pathogens; India ink stain; and cryptococcal antigen.
• India ink stain of the CSF reveals budding yeast in at least 50% of the cases.
• CSF evaluations in HIV-infected individuals may be relatively unremarkable; however, in most others, CSF abnormalities exist with a mild mononuclear pleocytosis, mildly elevated protein, and depressed glucose.
• Blood and CSF samples should be sent for fungal culture.

• Amphotericin, 0.3 to 1 mg/kg/d plus 5-fluorocytosine (5-FC), 37.5 mg/kg q6h. This regimen should be continued for a minimum of 6 weeks.
• In patients with HIV, maintenance therapy is recommended with fluconazole at 400 mg/d.
• Treatment of pulmonary Cryptococcus is recommended in the immunocompromised host. Treatment of bone or isolated visceral infection is also recommended with 6 to 8 weeks of amphotericin B.

Q: What are the sources of Cryptococcus in nature?
A: Pigeon droppings and soil.

Q: Can “normal” (immunocompetent) people get this infection? How long should it be treated?
A: Yes. Treat for 6 weeks.

Q: Should all patients with Cryptococcus be worked up for immunodeficiency?
A: Yes.

Aberg JA, Powderly WG. Cryptococcal disease: implications of recent clinical trials on treatment and management. AIDS Clin Rev 1997–1998;229–248.

Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 1989;321:794–799.

Dismukes WE. Cryptococcal meningitis in patients with AIDS. J Infect Dis 1988;157:624–628.

Saag MS, Powderly WG, Cloud GA, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. N Engl J Med 1992;326:83–89.

Wittner M. Cryptococcal disease. In: Feigen RD, Cherry JD, eds. Textbook of pediatric infectious diseases, vol. 2. Philadelphia: WB Saunders, 1992:1934–1939.