cryptococcosis

Definition

Cryptococcosis is an infection caused by inhaling the fungus Cryptococcus neoformans. It is one of the diseases most often affecting AIDS patients. Cryptococcosis may be limited to the lungs, but frequently spreads throughout the body. Although almost any organ can be infected, the fungus is often fatal if it infects the nervous system where it causes an inflammation of the membranes covering the brain and spinal cord (meningitis).

Description

The fungus causing cryptococcis, C. neoformans, is found worldwide in soil contaminated with pigeon or other bird droppings. It has also been found on unwashed raw fruit. Cryptococcosis is a rare disease in healthy individuals, but is the most common fungal infection affecting people with AIDS.

People with Hodgkin's disease or who are taking large doses of drugs that suppress the functioning of the immune system (corticosteroids, chemotherapy drugs) are also more susceptible to cryptococcal infection. Cryptococcosis is also called cryptococcal meningitis (when the brain is infected), BusseBuschke disease, European blastomycosis, torular meningitis, or torulosis.

Causes and symptoms

Once the cryptococcal fungus reaches the lungs, three things can happen. The immune system can heal the body without medical intervention, the disease can stay localized in the lungs, or it can spread throughout the body. In healthy people with normally functioning immune systems, the body usually heals itself, and the infected person notices no symptoms and has no complications (asymptomatic). The disease does not spread from one person to another.

Cryptococcosis is an opportunistic infection that puts people with immune system diseases at higher risk of developing more serious forms of the disease. In the United States, 6-10% of all patients with AIDS get cryptococcosis.

If the body does not heal itself, the fungus begins to grow in the lungs and form nodules that can be seen on chest x rays. In the early stages of infection, an individual usually only exhibits symptoms of a respiratory infection, such as a dry cough, so the disease is rarely diagnosed.

The fungus can remain dormant in the lungs and produce an active infection later if the immune system is weakened. If the disease becomes active, it can cause cryptococcal pneumonia in the lungs. Unfortunately, however, cryptococcal pneumonia has symptoms similar to other pneumonias (cough, chest pain, difficulty breathing), making it difficult to accurately diagnose. The infection can spread to other parts of the body, particularly the brain and central nervous system.

Most patients are not diagnosed as having cryptococcosis until they show signs of cryptococcal meningitis, or infection of the membranes surrounding the brain and spinal cord. Symptoms appear gradually over a period of two to four weeks. Fever and headache are the most common symptoms, occurring in about 85% of patients. Nausea, vomiting, unwanted weight loss, and fatigue are also common. Other symptoms seen in 25-30% of patients are blurred vision, stiff neck, aversion to light, and seizures. Since the symptoms of classic meningitis, such as stiff neck and aversion to light, do not occur in many patients, diagnosis is often delayed. In addition to meningitis, inflammation of the brain (encephalitis) and brain lesions called cryptococcomas or tortulomas can also develop.

In addition to the brain, the cryptococcal infection can spread to the kidneys, bone marrow, heart, adrenal glands, lymph nodes, urinary tract, blood, and skin. Often times preceding the development of cryptococcal meningitis, painless rashes and lesions that mimic other skin diseases, such as molluscum contagiosum, may develop. A small percentage of patients with brain infections show infections in other organs as well.

Diagnosis

Physicians who regularly work with AIDS patients have the most experience in diagnosing cryptococcosis. The preferred methods of diagnosis use simple and very accurate blood and cerebrospinal fluid (CSF) tests that detect the presence of an antigen produced by the fungus. The cerebrospinal fluid test is generally more sensitive to detecting the meningitis form of the infection. CSF is collected during a procedure called a lumbar puncture, during which an anesthetic is applied to a small area of the back near the spine and a needle is used to withdraw a sample of cerebrospinal fluid from the space between the vertebrae and the spinal cord. Once obtained, a small amount of ink (called India ink) is added to a sample of CSF or a sample prepared from skin lesions. If the fungus is present, it will become visible when the ink binds to the capsule or covering that surrounds the fungus. Faster results are obtained with the India ink test, but it is less accurate than the blood test (75-85% accuracy compared to 99% accuracy with the blood test) because some strains are not visible using this method. Antigen tests are routinely recommended for non-symptomatic patients with advanced AIDS.

Another way to diagnose cryptococcosis is to culture a sample of sputum, tissue from a lung biopsy, or CSF in the laboratory to isolate the fungus. Cultures are also done to assess the effectiveness of treatment.

Chest x rays are useful in assessing lung damage and may reveal a single mass or multiple distinct nodules, but the x ray alone does not lead to a definitive diagnosis of cryptococcosis.

Treatment

Once cryptococcosis is diagnosed, treatment begins with amphotericin B (Fungizone), sometimes in combination with 5-flucytosine (Ancobon). Amphotericin B is a powerful fungistatic drug with potentially toxic side effects, such as kidney toxicity and lower concentrations of an important blood component called hemoglobin. This medication can also cause fever, chills, nausea and vomiting, diarrhea, headache, and muscle aches. Treatment is generally given intravenously during a hospital stay and continues until the patient is stable or improving (no more than two to three weeks). 5-flucytosine is given orally. Patients may also receive other medication to minimize the side effects from these drugs.

Amphotericin B, with or without 5-flucytosine, is given for several weeks until the patient is stable, after which the patient receives oral fluconazole (Diflucan). Fluconazole is a broad-spectrum antifungal drug with few serious side effects. Patients with AIDS must continue taking fluconazole for the rest of their lives to prevent a relapse of cryptococcosis. Sometimes fluconazole is given to patients with advanced AIDS as a preventative (prophylactic) measure.

Because of the high cost of fluconazole, the manufacturer of the drug, Pfizer, has established a financial assistance plan to make the drug available at lower cost to those who meet certain criteria. Patients needing this drug should ask their doctors about this program.

Prognosis

Untreated cryptococcosis is always fatal. The acute mortality rate for patients with AIDS is 10-25%. Most deaths are attributable to cryptococcal meningitis and occur within two weeks after diagnosis. For AIDS patients who do not receive continued suppressive therapy (fluconazole), the relapse rate is 50-60% within six months and a shortened life expectancy. Once the cryptococcosis infection has been successfully treated, individuals may be left with a variety of neurologic symptoms, such as weakness, headache, and hearing or visual loss. In addition, fluid may accumulate around the brain (hydrocephalus).

Prevention

The best way to prevent cryptococcosis is to stay free of HIV infection. People with suppressed immune systems should try to stay away from areas contaminated with pigeon or other bird droppings, such as the attics of old buildings, barns, and areas under bridges where pigeons roost.