Cryptococcosis overview: Difference between revisions
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==Overview== | ==Overview== | ||
[[Cryptococcosis]] is an [[infection]] acquired by [[inhalation]] of soil [[Contamination|contaminated]] with the encapsulated [[yeast]] ([[fungus]]) ''[[Cryptococcus neoformans]]''. The [[immune response]] to [[cryptococcal infection]] is highly dependent on host [[T cell|T-cell]] function, | [[Cryptococcosis]] is an [[infection]] acquired by [[inhalation]] of soil [[Contamination|contaminated]] with the encapsulated [[yeast]] ([[fungus]]) ''[[Cryptococcus neoformans]]''. The [[immune response]] to [[cryptococcal infection]] is highly dependent on host [[T cell|T-cell]] function, [[Interferon-gamma|interferon-γ]] and [[TNF|TNF-α]] [[Cell signaling|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. ''[[Cryptococcus neoformans|C. neoformans]]'' can cause no [[infection]], latent [[infection]], or [[symptomatic]] disease. ''[[Cryptococcus neoformans|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, ''[[Cryptococcus neoformans|C. neoformans]]'' can [[Disseminated disease|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]]. [[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. | ||
== Historical Perspective == | == Historical Perspective == | ||
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== Classification == | == Classification == | ||
[[Cryptococcosis]] may be classified based on the site of [[infection]]. The clinical [[syndrome]] can be classified as [[pulmonary]], [[CNS]], or [[Disseminated disease|disseminated]] [[cryptococcosis]]. Another approach to the classification involves the [[species]] or variety of the ''[[Cryptococcus]]'' causative organism, including ''[[Cryptococcus neoformans]]'', ''[[Cryptococcus gattii]]'', and other, | [[Cryptococcosis]] may be classified based on the site of [[infection]]. The clinical [[syndrome]] can be classified as [[pulmonary]], [[CNS]], or [[Disseminated disease|disseminated]] [[cryptococcosis]]. Another approach to the classification involves the [[species]] or variety of the ''[[Cryptococcus]]'' causative organism, including ''[[Cryptococcus neoformans]]'', ''[[Cryptococcus gattii]]'', and other, rare species. | ||
== Pathophysiology == | == Pathophysiology == | ||
[[Infection (disambiguation)|Infective]] [[Cryptococcosis|cryptococcal]] [[species]] are ubiquitous and natural exposure by [[inhalation]] is very common. [[Cryptococci]] are [[intracellular]] [[pathogens]]. Once they are [[Phagocytosis|phagocytosed]], they germinate and multiply within the [[macrophages]]. The [[immune response]] to [[cryptococcal infection]] is highly dependent on host [[T-cell]] function | [[Infection (disambiguation)|Infective]] [[Cryptococcosis|cryptococcal]] [[species]] are ubiquitous and natural exposure by [[inhalation]] is very common. [[Cryptococci]] are [[intracellular]] [[pathogens]]. Once they are [[Phagocytosis|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 [[Tumor necrosis factor-alpha|TNF-α]] [[Cell signaling|signaling]]. Microscopically, ''[[Cryptococcus neoformans|Cryptococci]]'' are characterized by a thick [[mucopolysaccharide]] [[Capsule (anatomy)|capsule]] with a refractile center. | ||
== Causes == | == Causes == | ||
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== Epidemiology and Demographics == | == Epidemiology and Demographics == | ||
The [[prevalence]] of [[Cryptococcal infection|cryptococcal]] antigenemia among patients with [[HIV]] in the United States is approximately | The [[prevalence]] of [[Cryptococcal infection|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 == | ||
Risk factors for the development of [[cryptococcal infection]] include being [[immunocompromised]] and [[Inhalation|inhalational]] exposure (most commonly from dry bird droppings). | Risk factors for the development of [[cryptococcal infection]] include being [[immunocompromised]] and [[Inhalation|inhalational]] exposure (most commonly from dry bird droppings). | ||
== Screening == | == Screening == | ||
[[Asymptomatic]] [[Cryptococcal infection|cryptococcal]] antigenemia is very common in areas with [[Endemic (epidemiology)|endemic]] [[HIV AIDS|HIV/AIDS]], and is associated with increased [[mortality]] and [[incidence]] of [[Cryptococcal Meningitis|cryptococcal meningitis]]. Screening is not recommended for [[HIV AIDS|HIV/AIDS]] patients in the United States or Europe. However, screening may be beneficial in countries with limited [[HIV AIDS medical therapy|HAART]] availability, high levels of [[HIV AIDS medical therapy|antiretroviral drug]] [[Drug resistance|resistance]], and a high burden of disease. In the absence of symptoms, positive [[Cryptococcal infection|cryptococcal]] antigenemia should be treated with [[oral]] [[fluconazole]]. | [[Asymptomatic]] [[Cryptococcal infection|cryptococcal]] antigenemia is very common in areas with [[Endemic (epidemiology)|endemic]] [[HIV AIDS|HIV/AIDS]], and is associated with increased [[mortality]] and [[incidence]] of [[Cryptococcal Meningitis|cryptococcal meningitis]]. [[Screening (medicine)|Screening]] is not recommended for [[HIV AIDS|HIV/AIDS]] patients in the United States or Europe. However, [[Screening (medicine)|screening]] may be beneficial in countries with limited [[HIV AIDS medical therapy|HAART]] availability, high levels of [[HIV AIDS medical therapy|antiretroviral drug]] [[Drug resistance|resistance]], and a high burden of [[disease]]. In the absence of [[Symptom|symptoms]], positive [[Cryptococcal infection|cryptococcal]] antigenemia should be treated with [[oral]] [[fluconazole]]. | ||
== Natural History, Complications and Prognosis == | == Natural History, Complications and Prognosis == | ||
''[[Cryptococcus neoformans|C. neoformans]]'' can cause no [[infection]], latent [[infection]], or [[symptomatic]] disease. ''[[Cryptococcus neoformans|C. neoformans]]'' enters the body through the [[Respiratory system|respiratory]] route. [[Infection]] can present as [[pneumonia]]-like illness with symptoms such as [[cough]], [[fever]], [[chest pain]], and [[weight loss]]. If left untreated, ''[[Cryptococcus neoformans|C. neoformans]]'' can [[Disseminated disease|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. | ''[[Cryptococcus neoformans|C. neoformans]]'' can cause no [[infection]], latent [[infection]], or [[symptomatic]] disease. ''[[Cryptococcus neoformans|C. neoformans]]'' enters the body through the [[Respiratory system|respiratory]] route. [[Infection]] can present as [[pneumonia]]-like illness with [[Symptom|symptoms]] such as [[cough]], [[fever]], [[chest pain]], and [[weight loss]]. If left untreated, ''[[Cryptococcus neoformans|C. neoformans]]'' can [[Disseminated disease|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 == | == Diagnosis == | ||
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The symptoms of [[cryptococcosis]] depend on the site of [[infection]]/clinical syndrome, the [[virulence]] of the [[yeast]] [[Strain (biology)|strain]], and the [[Immune system|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 [[Disseminated disease|disseminate]] to the [[central nervous system]] and cause [[meningoencephalitis]] presenting with [[headache]], [[nausea]], [[vomiting]], [[Altered mental status|altered sensorium]], and focal [[neurological]] deficits. | The symptoms of [[cryptococcosis]] depend on the site of [[infection]]/clinical syndrome, the [[virulence]] of the [[yeast]] [[Strain (biology)|strain]], and the [[Immune system|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 [[Disseminated disease|disseminate]] to the [[central nervous system]] and cause [[meningoencephalitis]] presenting with [[headache]], [[nausea]], [[vomiting]], [[Altered mental status|altered sensorium]], and focal [[neurological]] deficits. | ||
=== Physical Examination === | === Physical Examination === | ||
Physical examination findings in patients with [[Meningitis|cryptococcal meningitis]] include [[fever]], [[nystagmus]], [[papilledema]], and [[Cranial nerves|cranial nerve]] deficits. [[Cutaneous]] [[cryptococcal infection]] presents with [[erythematous]] [[papules]], [[pustules]], [[nodules]], and [[ulcers]]. [[Rales]] can be heard on [[auscultation]] in [[pulmonary]] [[cryptococcus infection]]. | Physical examination findings in patients with [[Meningitis|cryptococcal meningitis]] include [[fever]], [[nystagmus]], [[papilledema]], and [[Cranial nerves|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 === | === Laboratory Findings === | ||
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There are no associated other imaging findings with [[Cryptococcosis|cryptococcal infection]]. | There are no associated other imaging findings with [[Cryptococcosis|cryptococcal infection]]. | ||
=== Other Diagnostic studies === | === 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 infection|cryptococcal]] [[antigen]] in [[CSF]], and a positive culture for | 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 infection|cryptococcal]] [[antigen]] in [[CSF]], and a positive [[Culture media|culture]] for [[Cryptococcus neoformans|''Cryptococcus neoformans'']]. | ||
== Treatment == | == Treatment == | ||
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=== Surgery === | === 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 therapy. | 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 == | == Prevention == | ||
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=== Secondary Prevention === | === Secondary Prevention === | ||
Secondary preventive measures for [[Cryptococcosis|cryptococcal infection]] are the same as primary prevention measures. | [[Secondary prevention|Secondary preventive]] measures for [[Cryptococcosis|cryptococcal infection]] are the same as [[primary prevention]] measures. | ||
== References == | == References == | ||
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[[Category:Fungal diseases]] | [[Category:Fungal diseases]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Emergency medicine]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | |||
[[Category:Pulmonology]] | |||
[[Category:Neurology]] | |||
[[Category:Dermatology]] | |||
Latest revision as of 21:10, 29 July 2020
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, 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 pulmonary, CNS, or disseminated cryptococcosis. Another approach to the classification involves the species or variety of the Cryptococcus causative organism, including Cryptococcus neoformans, Cryptococcus 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.