Infection with either C. neoformans var neoformans or C. neoformans var gattii causes cryptococcal disease. The most common pathogen that infects patients who are immunocompromised is C. neoformans var neoformans. The most common pathogen that infects patients who are immunocompetent is C. neoformans var gattii.

The C. neoformans enters the body via the lungs, and causes a pulmonary infection. After the patient develops a pulmonary infection, the cryptococci yeast spreads throughout the body and may infect any organ. The organs most often involved include the central nervous system (CNS), bones, prostate, eyes and skin. The CNS is the main site of symptomatic infections in both immunocompetent and immunocompromised individuals.

Cryptococcal CNS infections usually involve both the brain and meninges (membranes that surround the brain and spinal cord). Immunocompetent hosts may present with either meningitis or focal cryptococcomas. Meningitis manifests with diffuse, nonfocal findings (such as altered mental status and vomiting), whereas cryptococcomas often manifest with focal neurologic (brain) defects.

General: Cryptococcosis usually starts with a pulmonary infection (in the lungs), which usually spreads to the central nervous system (CNS). If left untreated, the infection can continue to spread to other organs in the body, including the skin, prostate and medullary cavity (bone marrow) of the bones.

Pulmonary: Symptoms of cryptococcal pulmonary (lung) disease vary. Some patients are asymptomatic (experience no symptoms) while others, especially immunocompromised patients (like HIV/AIDS patients and organ transplant recipients), suffer from acute respiratory distress syndrome. Sometimes pulmonary disease manifests as a progressive mass that compresses important body tissues in the chest such as the vena cava (main veins to the heart).

Common symptoms include fever, general feeling of discomfort, dry cough, pleuritic pain (pain in the membrane surrounding the lungs), and rarely, blood in the sputum.

Less common symptoms include rales (crackling sound that occur when air moves through fluid-filled lungs), pleural effusions (fluid between the lining of the lung and the lining of the inside wall of the chest), cavitation (formation of cavities in a body tissue or an organ) and enlarged lymph nodes.

Central nervous system (CNS): Meningitis and meningoencephalitis are the most common manifestations of an infection that has spread to the CNS. This form of infection is fatal without treatment after two weeks to several years of the onset of symptoms.

Symptoms vary depending on the individual's overall health prior to infection. Some patients who are HIV-positive may have minimal or nonspecific symptoms when they are diagnosed with the condition. Common symptoms include headache, altered mental status (such as personality changes), confusion, lethargy, reduced consciousness, coma, nausea and vomiting. Other, less common, symptoms include fever, stiff neck, hearing defects and seizures. Dementia may indicate a condition called hydrocephalus (accumulation of cerebrospinal fluid in the brain) as a late complication.

Blurred vision, photophobia and double vision, may occur secondary to arachnoiditis (inflammation and scarring of the membranes covering the spinal cord), inflammation of the optic nerve and chorioretinitis (inflammation behind the retina).

Disseminated: If the infection continues to spread after lung and CNS infection, the skin, prostate and medullary cavity of the bones are the most likely organs to be affected next. Cutaneous (skin) manifestations occur in 10-15% of cases and usually take the form of papules, pustules, nodules, ulcers or draining sinuses. Cellulitis (inflamed connective tissue) with necrotizing vasculitis (inflamed blood vessels) is reported in patients who undergo organ transplantation.

Bone lesions develop in 5-10% of the patients. Bone lesions usually cause the breakdown of the bone, and they may be confused with tuberculosis or neoplasm (tumor growth).

Other less common forms of cryptococcosis include myocarditis (inflamed heart), chorioretinitis (inflamed choroid layer behind the retina in the eye), inflamed liver, peritonitis (inflamed lining of the abdominal cavity), kidney infection, enlarged prostate, myositis (inflamed muscle tissue) or adrenal involvement.

General: The diagnosis is made on the basis of a series of tests, including a cerebrospinal fluid (CSF) culture and positive identification of the yeast.

It may be more difficult to diagnose AIDS patients who have cryptococcal meningitis because abnormalities in the CSF may have been caused by a different type of infection.

Lumbar puncture (spinal tap): A lumbar puncture, also called a spinal tap, may be performed to detect abnormalities in the cerebrospinal fluid (CSF). During the procedure, a needle is inserted in the lower back between two vertebrae to remove a sample of CSF. The CSF is then tested for the presence of the disease-causing yeast.

Blood culture: A sample of blood is taken from the patient. The sample is then taken to a laboratory and placed in conditions that allow the yeast to grow. A positive culture will identify the disease-causing organism.

Imaging studies: A computerized tomography (CT) scan and magnetic resonance imaging (MRI) are important diagnostic techniques in any patient who has HIV/AIDS with neurologic (brain) dysfunction. Several studies have shown that MRI is better than a CT scan in detecting abnormalities in CNS cryptococcosis. Normal MRI findings do not rule out a diagnosis of CNS cryptococcosis because the typical features of this infection occur in only 40% of patients. Intracranial mass lesions occur frequently in patients with AIDS.