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Latest revision as of 21:10, 29 July 2020


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Cryptococcosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Cryptococcosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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Overview

Cryptococcosis is an infection acquired by inhalation of soil contaminated with the encapsulated yeast (fungus) Cryptococcus neoformans. The immune response to cryptococcal infection is highly dependent on host T-cell function, interferon-γ and TNF-α signaling is impaired in immunocompromised patients, resulting in disease. The overall incidence of cryptococcosis is estimated to be 0.4 to 1.3 cases per 100,000 persons yearly in the United States. C. neoformans can cause no infection, latent infection, or symptomatic disease. C. neoformans enters the body through the respiratory route, and infection can present as pneumonia-like illness with symptoms such as cough, fever, chest pain, and weight loss. If left untreated, C. neoformans can disseminate to the central nervous system, causing meningoencephalitis. Prognosis is poor without treatment, with a mortality rate reaching 10 to 30% within 3 weeks of presentation. The standard regimen of treatment in non-AIDS patients is intravenous amphotericin B combined with oral flucytosine. AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore, after initial treatment as above, oral fluconazole can be used.

Historical Perspective

Cryptococci, initially thought to be of the Saccharomyces genus, were first identified in 1894 by German pathologist Otto Busse in a patient with chronic periostitis of the tibia. In 1901, Jean Paul Vuillemin, a French mycologist, moved the yeast-like fungus to the genus Cryptococcus due to the absence of ascospores in its life cycle, a defining feature of Saccharomyces.

Classification

Cryptococcosis may be classified based on the site of infection. The clinical syndrome can be classified as pulmonaryCNS, or disseminated cryptococcosis. Another approach to the classification involves the species or variety of the Cryptococcus causative organism, including Cryptococcus neoformansCryptococcus gattii, and other, rare species.

Pathophysiology

Infective cryptococcal species are ubiquitous and natural exposure by inhalation is very common. Cryptococci are intracellular pathogens. Once they are phagocytosed, they germinate and multiply within the macrophages. The immune response to cryptococcal infection is highly dependent on host T-cell function, interferon-γ and TNF-α signaling. Microscopically, Cryptococci are characterized by a thick mucopolysaccharide capsule with a refractile center.

Causes

Cryptococcosis is an infection acquired by inhalation of soil contaminated with the encapsulated yeast (fungus) Cryptococcus neoformans.

Differentiating Cryptococcosis from other Diseases

Cryptococcosis is more common among immunocompromised patients who are at high risk for other fungal, bacterial, and viral infections. Cryptococcal meningitis can be indistinguishable from bacterial or viral meningitis. Cryptococcosis must be differentiated from diseases that cause symptoms of lower respiratory tract infection (fever, dyspnea, cough) and meningitis (fever, headache, neck stiffness, focal neurological deficits) such as coccidioidomycosis, histoplasmosis, tuberculosis, and community/hospital-acquired pneumonia. Cutaneous cryptococcosis in HIV/AIDS patients must be differentiated from molluscum contagiosum and Kaposi's sarcoma.

Epidemiology and Demographics

The prevalence of cryptococcal antigenemia among patients with HIV in the United States is approximately 2900 per 100,000 patients. The overall annual incidence is estimated to be 0.4 to 1.3 cases per 100,000 individuals in the United States. Cryptococcosis has no age, gender, or racial predilection.

Risk Factors

Risk factors for the development of cryptococcal infection include being immunocompromised and inhalational exposure (most commonly from dry bird droppings).

Screening

Asymptomatic cryptococcal antigenemia is very common in areas with endemic HIV/AIDS, and is associated with increased mortality and incidence of cryptococcal meningitis. Screening is not recommended for HIV/AIDS patients in the United States or Europe. However, screening may be beneficial in countries with limited HAART availability, high levels of antiretroviral drug resistance, and a high burden of disease. In the absence of symptoms, positive cryptococcal antigenemia should be treated with oral fluconazole.

Natural History, Complications and Prognosis

C. neoformans can cause no infection, latent infection, or symptomatic disease. C. neoformans enters the body through the respiratory route. Infection can present as pneumonia-like illness with symptoms such as cough, fever, chest pain, and weight loss. If left untreated, C. neoformans can disseminate to the central nervous system and cause meningoencephalitis. Prognosis is poor without treatment, with a mortality rate reaching 10 to 30% within 3 weeks of presentation.

Diagnosis

History and Symptoms

The symptoms of cryptococcosis depend on the site of infection/clinical syndrome, the virulence of the yeast strain, and the immune status of the host. Patients may be completely asymptomatic, have latent infection, or have symptomatic disease. Cryptococcus enters the body through the respiratory route. Infection can present as pneumonia-like illness with fever, cough, sputum production, and chest pain. Cryptococcus can also disseminate to the central nervous system and cause meningoencephalitis presenting with headache, nausea, vomiting, altered sensorium, and focal neurological deficits.

Physical Examination

Physical examination findings in patients with cryptococcal meningitis include fever, nystagmus, papilledema, and cranial nerve deficits. Cutaneous cryptococcal infection presents with erythematous papules, pustules, nodules, and ulcers. Rales can be heard on auscultation of the chest in pulmonary cryptococcus infection.

Laboratory Findings

Cryptococcal disease can be diagnosed through culture, CSF microscopy, or by cryptococcal antigen (CrAg) detection.

Chest X-Ray

Chest radiography in a patient with pulmonary cryptococcosis may demonstrate interstitial infiltrates, pleural effusion, or hilar lymphadenopathy.

CT

The most common CT findings in patients with pulmonary cryptococcosis are pulmonary nodules and pulmonary opacities that range from a perihilar interstitial pattern to an area of dense alveolar consolidation.

MRI

Common MRI findings in patients with cryptococcal meningitis include Virchow-Robin dilatation, hydrocephalus, intracerebral nodules, and pseudocysts.

Other Imaging Findings

There are no associated other imaging findings with cryptococcal infection.

Other Diagnostic studies

Other diagnostic studies helpful diagnosing cryptococcal infection include demonstration of the budding yeast on an India ink stain, staining the polysaccharide cell wall using mucicarmine stain, detection of cryptococcal antigen in CSF, and a positive culture for Cryptococcus neoformans.

Treatment

Medical Therapy

The standard regimen of treatment in non-AIDS patients is intravenous amphotericin B combined with oral flucytosine. AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore, after initial treatment as above, oral fluconazole can be used.

Surgery

Surgical excision of cryptococcoma is recommended if the lesions are larger than 3 cm, accessible lesions have a mass effect or compress vital structures, or the size of the cryptococcoma fails to decrease after 4 weeks of medical therapy.

Prevention

Primary prevention

It is recommended that patients with CD4 counts ≤ 100 cells/μl should have routine cryptococcal antigen screening and patients with positive results should be offered preemptive anti-fungal therapy.

Secondary Prevention

Secondary preventive measures for cryptococcal infection are the same as primary prevention measures.

References