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Cryptococcosis

Author: Vanessa Ngan, Staff Writer, 2005.


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What is cryptococcosis?

Cryptococcosis is a fungal infection caused by inhaling the fungus Cryptococcus neoformans, which is primarily found in soils enriched with pigeon droppings. In moist or desiccated pigeon dropping, C. neoformans may remain viable for 2 years or longer.

Two varieties of C. neoformans exist – neoformans and gattii. C. neoformans var neoformans is the most common variety and mainly affects immunosuppressed patients such as those with human immunodeficiency virus (HIV) infection and AIDS. C. neoformans var gattii is much less common, but affects mainly immunocompetent individuals. This variety is restricted to subtropical and tropical areas and the fungus is found on eucalyptus trees and in the surrounding air.

What are the causes and risk factors for cryptococcosis?

The most common cryptococcosis infections (C. neoformans var neoformans) affect people with immunodeficiency, for example, patients on high doses of corticosteroids, cancer chemotherapy patients, organ transplantation patients, and patients with acquired immune deficiency (AIDS) and HIV infection. With the global emergence of AIDS, cryptococcosis is now one of the most common life-threatening fungal infections in these patients.

Infection is primarily through inhalation of cryptococcus spores released from soil and bird droppings. It occurs in both humans and animals, but animal-to-human and human-to-human transmission via respiratory droplets has not been documented. Transmission via organ transplantation has been reported when infected donor organs were used. Infection via cuts through the skin is not common but may occur.

What are the clinical features of cryptococcosis?

The signs and symptoms of the disease are dependent on the site of infection. There are several main sites of infection.

Site of infection Features
Lung
  • In immunocompetent patients no signs or symptoms may be present. Often these patients will recover spontaneously without any medication.
  • Immunosuppressed patients may present with mild-to-moderate symptoms, including fever, malaise, dry cough, chest pain.
  • Severe infection may lead to pneumonia or adult respiratory distress syndrome.
Central nervous system (CNS)
  • Meningitis is the most common presentation.
  • Signs and symptoms include headache, altered mental status, confusion, lethargy, nausea and vomiting, blurred vision or double vision, seizures and coma.
  • This form of infection is fatal without appropriate therapy. Death may occur from 2 weeks to several years after the onset of symptoms.
Disseminated (widespread, involving other organs)
  • In severe infections, pulmonary and CNS disease is often associated with disseminated disease.
  • Organs most commonly affected include the skin, prostate, and medullary cavity of the bones

Cryptococcal skin infection

  • Skin infection occurs in 10–15% of patients infected with C. neoformans.
  • In immunocompetent patients, skin may be the only site of infection.
  • In immunosuppressed patients, especially those with HIV infection or AIDS, skin infection is usually a sign of disseminated disease.
  • Skin infection presents as:
    • Papules, pustules, nodules and ulcers
    • Bleeding into the skin, presenting as petechiae or ecchymoses.

How is cryptococcosis diagnosed?

The following laboratory and radiology tests are performed to assist in the diagnosis of cryptococcal disease.

  • Sputum culture and stain
  • Lung biopsy
  • Bronchoscopy
  • CSF culture and stain
  • Chest x-ray

Skin biopsy shows characteristic histopathology.

What is the treatment for cryptococcosis?

Treatment of cryptococcal disease depends on the patient’s immunological status and the site of infection. It is based on the following categories of infection.

  1. Pulmonary cryptococcosis in an immunocompetent patient
  2. Pulmonary cryptococcosis in an immunosuppressed patient
  3. CNS cryptococcosis
  4. Disseminated nonpulmonary, non-CNS cryptococcosis

Immunocompetent patients with asymptomatic pulmonary disease do not usually require any treatment. If the disease does not resolve spontaneously then the antifungal fluconazole may be given for 3–6 months.

Treatment goals for categories 2,3 and 4 differ on whether or not the patient also has HIV/AIDS. The goal in infected patients with HIV/AIDS is to first control the infection, followed by life-long treatment to suppress C. neoformans. For patients with cryptococcal disease not complicated by HIV/AIDS, the treatment goal is to eradicate the fungi and achieve a permanent cure.

Several antifungal medications are used.

  • Intravenous amphotericin B is the drug of choice for the initial therapy of disseminated, pulmonary and CNS cryptococcosis.
  • Flucytosine should be used in conjunction with amphotericin B.
  • Oral fluconazole can be used in less severe infections and is used for life-long treatment to prevent relapses.

 

References

  • Book: Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth edition. Blackwell Scientific Publications.

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