Cryptococcosis overview: Difference between revisions
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The standard regimen of treatment in non-[[HIV AIDS|AIDS]] patients intravenous [[Amphotericin B|Amphotericin]] B combined with oral [[ | The standard regimen of treatment in non-[[HIV AIDS|AIDS]] patients intravenous [[Amphotericin B|Amphotericin]] B combined with oral [[Flucytosine]]. [[HIV AIDS|AIDS]] patients often have a reduced response to [[Amphotericin B]] and [[Flucytosine]], therefore after initial treatment as above, oral [[Fluconazole]] can be used. | ||
=== Surgery === | === Surgery === | ||
Revision as of 19:54, 24 July 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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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, and interferon-γ and TNF-α signaling which is impaired in immunocompromised states, resulting in disease. The overall incidence is estimated to be 0.4 to 1.3 cases per 100,000 population yearly in the United States. C. neoformans can either 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 causing meningoencephalitis. Prognosis is poor without treatment with a mortality reaching 10 to 30% within 3 weeks of presentation. The standard regimen of treatment in non-AIDS patients 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, transferred 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 i.e. the clinical syndrome into pulmonary, CNS, or disseminated cryptococcosis. Another approach to the classification involves the species or variety of the cryptococcus causative organism and includes Cryptococcus neoformans, Cryptococcus gattii, and other rarer 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, and interferon-γ and TNF-α signaling. Microscopically, cryptococci are characterized by a thick mucopolysaccharde 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 2.9%. The overall incidence is estimated to be 0.4 to 1.3 cases per 100,000 population yearly in the United States. Cryptococcosis has no age, gender, or race predilection.
Risk Factors
Risk factors for the development of cryptococcal infections include immunocompromised states as well as inhalational exposure (most commmonly 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 either 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 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, or may have latent infection or 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 will demonstrate erythematous papules, pustules, nodules, and ulcers. Rales can be heard on auscultation 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 or 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 for diagnosis of cryptococcal infection include demonstration of the budding yeast on 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 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 cyptococcoma is recommended if the lesions are larger than 3cm or accessible lesions with mass effect or compression of vital structures or failure to reduce the size of the cryptococcoma after 4 weeks of 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 result are offered preemptive anti-fungal therapy.
Secondary Prevention
Secondary preventive measures for cryptococcal infection are the same as primary prevention.