Cryptococcus neoformans

Notes plus proving info from Jeremy Sherr; Unpublished.
Taxonomic classificationKingdom: FungiPhylum: Basidimycota
Subphylum: Basidimycotina
Order: Sporidiales
Family: Sporidiobolaceae
Genus: Filobasidiella (Cryptococcus)Homeopathic indications:chronic fatigue
can’t string thoughts together; rambling speech, obfuscation
sudden loss of memory
alzheimers
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overview:
debilitated
darkness- thriving with darkness
death- holder for death
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chest pains- severe and debilitating***
pleural pains- chronic
chest problems
dry weak chronic cough
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(From new proving)
Outsider, stays on the outside, fears being seen, netherworld
Conduits between things
Bringing something to something else
going from one place to another, in between, float, in the stars, dismembered body,
(vampires)
another dimension, or at the basis of the formation of structure
outside of house, coming in
water, boats, ocean
safety= protected, wanting someone else to look out for them- but inside vulnerable
on the outside observing- not participating, planning, etc., disempowered to power
black, black tubes, or pink
***invasion, feeling of being invaded,
averse being invaded, invasive themselves
invasive then retreat
(interconnection then disconnection)dream everything enlarged, so enlarged can’t walk through it“dreamed the moon took up half horizon
distorted size dreams
distorted images in dreams
another dream where size of surroundings too big to walk through
everything was just bigger”cf Agaricusdreams where they are killed in the dream, being shot
dreams sitting by water
anxiety can’t get everything done
deserving
fighting for their rights, even though very weak- but confused about them
accused of being trouble maker
ailments from being accused
accused of being evil, darkTheme in proving: Split and separateSee VERTICAL – HORIZONTAL:
LEFT – RIGHT: Left – right confusion or split
HIGH UP – LOW DOWN: Up-down split; Disembodied heads, separated from body, emotionally detached; Flying, or floating in the air, or in space
See also INCLUSION - EXCLUSIONSee also AFFINITIES AND PATHOLOGY: PATHOLOGY REFERRED TO: Fissures, cracks, splitsDream: I am the dreamer and the dream. No separation.
16, 30c, 06:XX:XX
Also part of society or not part of society
underground
confusion of being included or excludedexhaustion on working; concentratingblurred vision; episodicNUMBER 3triangles
triangular relationships-----CONFUSION OF IDENTITYALIENATIONSPLIT, SEPARATE AND MOVING IN THE OPPOSITE DIRECTIONSWITCHING POLARITY AND ALTERNATIONELECTRICITY AND RADIATIONINSULATING MATERIALSNETWORKS, CONNECTIONS AND COMMUNICATIONSPRESERVATION AND TRANSMISSION OF INFORMATIONREPRODUCTION AND GENETICSSAFE – RISKYHIDDEN – EXPOSEDINCLUSION – EXCLUSIONDIRTY AND DISGUSTINGSEXUALITY, SEX AND GENITALIASTRAIGHT – BENTTIME AND SPACEEMPTINESSDRUGSPASSAGEWAYS AND ACCESS PORTALSJOURNEYS AND TRIPSFUEL AND POLLUTIONEMBARKATION AND DISEMBARKATIONBORDERS AND BOUNDARIESPENETRATION AND INSERTIONINVASIONVIOLENCE AND DEATHMAGIC, RITUALS AND SACRIFICEMIRRORS AND MIRROR IMAGESMOON – FIREBLACK AND WHITE OR BRIGHT AND COLOURFULCREATURESSPONGESWET – DRYVERTICAL – HORIZONTALANGLES AND PERSPECTIVESBIG – SMALLFOCUSED – SPREAD OUTCHANGING FORM AND RENEWALOLD – YOUNGLACK OF CONSCIOUS AWARENESSLEARNINGLAW AND ORDERACTION AND REACTION, KARMA – VIPARKAOTHER DIMENSIONSONE, 2, 3, FOUR OR FIVEDescription and Natural HabitatsCryptococcus is an encapsulated yeast. Following its first identification in nature from peach juice samples, the major environmental sources of Cryptococcus neoformans have been shown to be either soil contaminated with pigeon droppings (Cryptococcus neoformans var. neoformans) or eucalyptus trees and decaying wood forming hollows in living trees (Cryptococcus neoformans var. gattii) [346, 387, 1247, 1350]. Cryptococcus neoformans var. gattii was also isolated from goats with pulmonary disease [178].SpeciesThe genus Cryptococcus includes around 37 species. Among these, Cryptococcus neoformans is the only species that is pathogenic and will be discussed in this page. It has four serotypes (A to D). Serotyping is based on capsular agglutination reactions and can be detected by a dot enzyme assay [197]. Cryptococcus neoformans was generally accepted to include two varieties; var. gattii and var. neoformans [1266]. Until recently and traditionally, serotypes A and D were included in var. neoformans while serotypes B and D were included in var. gattii. However, in addition to the previously observed phenotypic differences, recent molecular studies have detected significant genetic variations between the two serotypes. Thus, it was recently proposed that a new variety, var. grubii, be created to contain serotype A [723]. This leaves serotype D as the sole serotype in var. neoformans.The two varieties, neoformans and gattii are morphologically similar, except that basidiospores of var. neoformans are round and those of var. gattii are more elliptical in shape. The definitive identification of the two varieties is possible by biochemical tests, such as resistance to canavanine, use of glycine as the sole carbon and nitrogen source, and resistance of their urease enzymes to EDTA [439].Among the other Cryptococcus spp. are Cryptococcus albidus, Cryptococcus laurentii, Cryptococcus terreus, Cryptococcus uniguttulatus, Cryptococcus luteolus and Cryptococcus gastricus [1234].The teleomorphic (sexual) reproductive phase of Cryptococcus that occurs in nature constitutes the genus Filobasidiella. If the strains of serotypes A or D mate with each other, Filobasidiella neoformans var. neoformans is the teleomorph. Similarly, the mating of serotypes B or C forms the teleomorph called Filobasidiella neformans var. bacillispora [439].SynonymsSee the summary of synonyms and teleomorph-anamorph relations for the Cryptococcus spp.Pathogenicity and Clinical SignificanceCryptococcus neoformans is the causative agent of cryptococcosis. Given the neurotropic nature of the fungus, the most common clinical form of cryptococcosis is meningoencephalitis. The course of the infection is usually subacute or chronic. Cryptococcosis may also involve the skin, lungs, prostate gland, urinary tract, eyes, myocardium, bones, and joints [146, 150, 164, 194, 321, 602, 905, 1220, 1560, 1978, 2035].The most commonly encountered predisposing factor for development of cryptococcosis is AIDS [2]. Less commonly, organ transplant recipients or cancer patients receiving chemotherapeutics or long-term corticosteroid treatment may develop cryptococcosis [439, 1175, 2174].The polysaccharide capsule and phenol oxidase enzyme of Cryptococcus neoformans, as well as its ability to grow at 37°C, are its major virulence factors [423, 1680]. Recent data suggest that phospholipase enzymes may also play a role as one of the potential virulence factors [788]. The infection commonly starts following inhalation of the yeasts [439]. Phenol oxidase enzyme functions in production of melanin. The melanizing enzyme presumably prevents formation of toxic hydroxy radicals and thus protects the fungal cell from oxidative stress as well as the immune defense mechanisms of the host [370, 572, 1051].Macroscopic FeaturesColonies of Cryptococcus neoformans are fast growing, soft, glistening to dull, smooth, usually mucoid, and cream to slightly pink or yellowish brown in color. The growth rate is somewhat slower than Candida and usually takes 48 to 72 h. It grows well at 25°C as well as 37°C. Ability to grow at 37°C is one of the features that differentiates Cryptococcus neoformans from other Cryptococcus spp. However, temperature-sensitive mutants that fail to grow at 37°C in vitro may also be observed [199]. At 39-40°C, the growth of Cryptococcus neoformans starts to slow down [439, 1234].Microscopic FeaturesOn cornmeal tween 80 agar, Cryptococcus neoformans produces round, budding yeast cells. No true hyphae are visible. Pseudohyphae are usually absent or rudimentary. The capsule is best visible in India ink preparations. The thickness of the capsule is both strain-related and varies depending on the environmental conditions. Upon growth in 1% peptone solution, production of capsule is enhanced [1234].Histopathologic FeaturesSee our histopathology page.Compare toCryptococcus neoformans should be differentiated from other clinically encountered yeasts, such as Blastoschizomyces, Geotrichum, Malassezia, Rhodotorula, Saccharomyces, and Trichosporon. Morphology on cornmeal tween 80 agar, capsule production, urease activity, ability to grow in presence of cycloheximide, growth pattern in Sabouraud broth, and fermentation assimilation profiles help in definitive identification of Cryptococcus neoformans.Microscopically, globose to ovoid yeast cells that have a capsule, producing neither well-developed pseudohyphae nor true hyphae are typical for Cryptococcus neoformans. Cryptococcus neoformans differs from Candida by not forming well-developed pseudohyphae. The lack of arthroconidia differentiates it from Trichosporon and Geotrichum, the two genera that produce abundant arthroconidia [1234].Biochemically, the members of the genus Cryptococcus are unable to ferment sugars, but do assimilate inositol and produce urease. Carotenoid pigment production is extremely variable. Cryptococcus neoformans produces phenoloxidase enzyme that results in production of melanin and thus a brown to black discoloration of the colony when it is grown on caffeic acid agar or bird seed agar. Cryptococcus differs from Rhodotorula by assimilating inositol, and from Candida glabrata by assimilating inositol and being urease positive [1234].Laboratory PrecautionsNo special precautions other than general laboratory precautions are required.SusceptibilityPlease see our extended discussion of the usual susceptibility patterns of Cryptococcus spp.SearchCryptococcosis Disease-disseminated:
Definition Return to topCryptococcosis is a rare fungal infection caused by inhaling the fungus, Cryptococcus neoformans.Causes, incidence, and risk factors Return to topCryptococcus neoformans, the fungus that causes this disease, is ordinarily found in soil. Once inhaled, infection with cryptococcosis may heal on its own, remain localized in the lungs, or spread throughout the body (disseminate).Most cases occur in people whose resistance to infection is lowered (such as by HIV infection, high doses of corticosteroid medications, cancer chemotherapy, or Hodgkin's disease).In people with normal immune systems, the pulmonary (lung) form may have no symptoms. However, in people with impaired immune systems, the cryptococcus organism may spread to the brain.The onset of neurological symptoms is gradual. The majority of people with this condition have meningoencephalitis (swelling and irritation of the brain and spinal cord) at the time of diagnosis.Cryptococcus is one of the most common life-threatening fungal infections in AIDS patients.Symptoms Return to topChest painDry cough
Headache
Nausea
Confusion
Blurred vision or double vision (diplopia)
Fatigue
Fever
Unusual and excessive sweating at night
Glands, swollen WITHOUT nearby areas appearing infected (e.g., red, painful, swollen)
Prolonged bleeding, bruising easily
Skin rash may be present
Skin rash or lesion - pinpoint red spots (petechiae)
Bleeding into the skin
Bruises (ecchymoses)
Unintentional weight loss
Appetite, loss
Abdominal fullness prematurely after meals
Abdominal pain
Abdomen, swollen
Weakness
Bone pain or tenderness of the breastbone (sternum)
Numbness and tingling
Nerve pain or pain along the path of a specific nerve
Pain along a nerve root (major pathway from the spinal cord)
Note: In individuals with normal immune systems there may be no symptoms
Signs and tests Return to topSputum culture and stainLung biopsy
Bronchoscopy
CSF culture and stain
Chest X-ray
Treatment Return to topSome infections require no treatment. However, medical observation should continue for a year to detect any progression of the disease. If pulmonary lesions are present or the disease spreads, antifungal medications are prescribed, and treatment with these agents may be prolonged.Medications include:Amphotericin BFlucytosine
Fluconazole
Expectations (prognosis) Return to topCentral nervous system involvement often has a fatal outcome, or leads to permanent damage.Complications Return to topRelapse of infectionMeningitis
Permanent brain or nerve damage
Side effects of medications (such as Amphotericin B) can be severe
Calling your health care provider Return to topCall your health care provider if symptoms develop that are suggestive of cryptococcosis, particularly if you have an impaired immune system.Prevention Return to topMinimize doses of corticosteroid medications. Safer sex practices reduce the risk of acquiring HIV and the subsequent opportunistic infections associated with a weakened immune system.Update Date: 7/16/2004
Updated by: Daniel Levy, M.D., Ph.D., Infectious Diseases, Greater Baltimore Medical Center, Baltimore, MD. Review provided by VeriMed Healthcare Network.CryptococcosisClinical Features Initial pulmonary infection is usually asymptomatic. Most patients present with disseminated infection, especially meningoencephalitis. In the United States, 85% of cases occur in HIV-infected persons.
Etiologic Agent Cryptococcus neoformans.
Reservoir C. neoformans var. neoformans has been isolated from the soil worldwide, usually in association with bird droppings. Less common etiologic agent, C. neoformans var. gattii has been isolated from eucalyptus trees in tropical and sub-tropical regions.
Incidence 0.4-1.3 cases per 100,000 in the general population. Among persons with AIDS, the annual incidence is 2-7 cases per 1,000.
Sequelae Meningitis may lead to permanent neurologic damage. Mortality rate is about 12%.
Transmission Inhalation of airborne yeast cells and/or basidiospores.
Risk Groups Immunocompromised persons, especially those with HIV infection.
Surveillance Active, population-based surveillance in selected U.S. sites. No national surveillance exists.
Challenges Developing a cost-effective prevention strategy (although fluconazole is effective chemoprophylaxis for persons with AIDS, it does not affect survival and is not considered cost effectiveFrom: http://www.emedicine.com/med/topic482.htmAuthor: John W King, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center at Shreveport
Coauthor(s): Anurag Markanday, MD, Consulting Staff, Department of Internal Medicine, Section of Infectious Diseases, James Paton Memorial Hospital, Canada; Asad Khan, MD, Fellow, Department of Internal Medicine, Division of Infectious Diseases, Louisiana State University Health Science CenterJohn W King, MD, is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, and Sigma Xi
Editor(s): Jeffrey D Band, MD, Clinical Professor of Medicine, Wayne State University School of Medicine; Director, Division of Infectious Diseases and International Medicine, William Beaumont Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; John W King, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center at Shreveport; Eleftherios Mylonakis, MD, PhD, Graduate Assistant in Medicine, Instructor in Medicine, Division of Infectious Disease, Massachusetts General Hospital, Harvard University; and Burke A Cunha, MD, Professor of Medicine, State University of New York at Stony Brook School of Medicine; Chief, Infectious Disease Division, Vice-Chair, Department of Internal Medicine, Winthrop-University HospitalDisclosure INTRODUCTION Section 2 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous BibliographyBackground: Cryptococcus neoformans is an encapsulated yeast. A pathologist named Busse first described the yeast in 1894 in a paper he presented to the Greifswald Medical Society. Busse isolated the yeast from the tibia of a 31-year-old woman, noted its resistance to sodium hydroxide, and published the case report that same year. The following year, a surgeon named Buschke reported the same isolate from the same patient, thus establishing the early eponym of Busse-Buschke disease. This one case served to identify a new yeast and to prove its pathogenic potential.Since the initial reports, researchers have identified the diverse spectrum of host responses to cryptococcal infection. The responses range from a harmless colonization of the airways and asymptomatic infection of laboratory workers (resulting in a positive skin test result) to meningitis or disseminated disease. Although virulence for animals and, possibly, humans varies among strains of cryptococci, virulence probably plays a relatively small role in determining the outcome of an infection. The crucial factor is the immune status of the host. The most serious infections usually occur in patients with defective cell-mediated immunity. For example, patients with AIDS, patients undergoing organ transplantation, patients with reticuloendothelial malignancy, patients undergoing corticosteroid treatment (but not those with neutropenia or immunoglobulin deficiency), and patients with sarcoidosis experience the most serious infections.With the global emergence of AIDS, the incidence of cryptococcosis is increasing and now represents a major life-threatening fungal infection in these patients.MycologyC neoformans has 2 varieties—neoformans and gattii. The species has 4 serotypes based on antigenic specificity of the capsular polysaccharide; these include serotypes A and D (C neoformans var neoformans) and serotypes B and C (C neoformans var gattii). The C neoformans var neoformans is the most common variety in the United States and other temperate climates throughout the world and is found in aged pigeon droppings. C neoformans var gattii develops in tropical and subtropical climates and is not associated with birds, but it grows in the litter around certain species of eucalyptus trees (ie, Eucalyptus camaldulensis, Eucalyptus tereticornis).Worldwide, C neoformans var neoformans serotype A causes most cryptococcal infections in patients who are immunocompromised, including patients infected with HIV. For unknown reasons, C neoformans var gattii rarely infects persons with HIV infection and other patients who are immunosuppressed. Patients infected with C neoformans var gattii are usually immunocompetent, respond slowly to treatment, and are at risk for developing intracerebral mass lesions (eg, cryptococcomas).C neoformans reproduces by budding and forms round yeastlike cells that are 3-6 mm in diameter. Within the host and in certain culture media, a large polysaccharide capsule surrounds each cell. C neoformans forms smooth, convex, yellow or tan colonies on solid media at 20-37°C (68-98.6°F). This fungus is identified by its microscopic appearance, biochemical test results, and ability to grow at 37°C (98.6°F). Most nonpathogenic Cryptococcus strains do not grow at 37°C (98.6°F). In addition, C neoformans does not assimilate lactose and nitrates or produce pseudomycelia on cornmeal or rice-Tween agar.Most strains of C neoformans can use creatinine as a nitrogen source, which may partially explain the growth of the organism in creatinine-rich avian feces. Another useful biochemical characteristic of C neoformans, which distinguishes it from nonpathogenic strains, is its ability to produce melanin. The fungal enzyme phenol oxidase acts on certain substrates (eg, dihydroxyphenylalanine, caffeic acid) to produce melanin.In 1976, Kwon-Chung described the perfect (ie, sexual, teleomorphic) form of C neoformans, which was Filobasidiella neoformans. Prior to the identification of F neoformans, which is mycelial, C neoformans was considered monomorphic yeast. F neoformans var neoformans results from the mating of suitable strains of serotypes A and D. The perfect state of C neoformans var gattii is Filobasidiella bacillisporus and results from the mating of serotypes B and C. Some strains of A and D can mate with strains of B and C.EpidemiologyC neoformans is distributed worldwide. Most cases of cryptococcosis are from serotypes A and D. Serotypes B and C are restricted to tropical and subtropical areas and are isolated from certain species of eucalyptus trees and the air beneath them. C neoformans var neoformans, which is recovered from aged pigeon feces, bird nests, and guano, invariably is serotype A or D. Although serotypes A and D occur in high concentrations in the pigeon feces, the fungus does not infect the birds. In moist or desiccated pigeon excreta, C neoformans may remain viable for 2 years or longer. In saprobic environments, C neoformans grows unencapsulated; however, unencapsulated strains regain their virulence following reacquisition of their polysaccharide capsule. C neoformans var gattii usually causes disease in patients with intact cell-mediated immunity.Naturally occurring cryptococcosis occurs in both animals and humans, but animal-to-human transmission or person-to-person transmission via the pulmonary route has not been documented. Transmission via organ transplantation has been reported when infected donor organs were used. C neoformans var neoformans causes the vast majority of cryptococcal infections in hosts who are immunosuppressed, including patients with AIDS, but C neoformans var gattii causes 70-80% of cryptococcal infections occurring in hosts who are immunocompetent.No significant difference exists in the incidence of infection related to age, race, or occupation. Healthy persons with a history of exposure to pigeons or bird feces and laboratory workers exposed to an aerosol of the organism have a higher rate of positive delayed skin reaction to cryptococcal antigen or cryptococci. Occasionally, laboratory accidents result in transmission of C neoformans, but pulmonary and disseminated disease is rare in this setting. Accidental cutaneous inoculation with C neoformans causes localized cutaneous disease.Pathophysiology: Of the 19 species that comprise the genus Cryptococcus, human disease is associated only with C neoformans. Animal models provide much of the understanding of the pathogenesis and the host defense mechanisms involved in C neoformans infections. The organism primarily is transmitted via the respiratory route and not directly from one human to another. After inhaling C neoformans, the alveolar macrophages ingest the yeast. Phagocytosis and destruction of the unencapsulated yeast cells readily occur, whereas encapsulated organisms are more resistant to phagocytosis. A cryptococcal polysaccharide capsule has antiphagocytic properties and may be immunosuppressive. The antiphagocytic properties of the capsule block recognition of the yeast by phagocytes and inhibit leukocyte migration into the area of fungal replication.Host response to cryptococcal infection includes both cellular and humoral components. Animal models demonstrate that natural killer cells participate in the early killing of cryptococci and, possibly, antibody-dependent cell-mediated killing. In vitro monocyte-derived macrophages, natural killer cells, and T lymphocytes can inhibit or kill cryptococci. A successful host response includes an increase in helper T-cell activity, skin test conversion, and a reduction in the number of viable organisms in the tissues. In addition to cellular mechanisms, anticryptococcal antibodies and soluble anticryptococcal factors are described. Antibodies to a cryptococcal antigen and its complement play a critical role in enhancing the macrophage- and lymphocyte-mediated immune response to the organism. Researchers use monoclonal antibodies to capsular polysaccharide to passively immunize mice against C neoformans.C neoformans infection is usually characterized by little or no necrosis or organ dysfunction until late in the disease. Organ damage may accelerate in persons with heavy infections. The lack of identifiable endotoxins or exotoxins partly causes the absence of extensive necrosis early in cryptococcal infections. Organ damage is primarily from tissue distortion secondary to the expanding fungal burden. Extensive inflammation or fibrosis is rare. The characteristic lesion of C neoformans consists of a cystic cluster of yeast with no well-defined inflammatory response. Well-formed granulomas generally are not present.C neoformans can cause an asymptomatic pulmonary infection followed later by the development of meningitis, which is often the first indication of disease. If limited to the lungs, C neoformans infection may cause pneumonia, poorly defined mass lesions, pulmonary nodules, and, rarely, pleural effusion. Although immune defects are common in patients with meningitis or disseminated infection, patients with disease that is confined to the lungs are usually immunocompetent.Frequency:In the US: Prior to 1946, only 200 patients with cryptococcal disease were reported in the medical literature. The development and use of corticosteroids and improvement in patient survival with some malignancies increased the reported incidence of cryptococcal disease. Since the mid 1980s, most cryptococcal disease has occurred in patients with AIDS. A study published in March 2005 that reviewed data from 1981-2000, the first 2 decades of the AIDS epidemic, showed that the annual incidence per million person-years was 19 cases in men and 2.6 cases in women. The highest incidence occurred from 1981-1992, and then the incidence began to decline. In women, the peak incidence occurred in 1997. A decrease in the overall incidence in cryptococcal disease occurred and preceded the availability of highly active antiretroviral therapy for AIDS.
Today, approximately 7-15% of patients with AIDS develop cryptococcal infections. In 1993, the US Centers for Disease Control and Prevention reported that 6% of 274,150 patients with AIDS developed cryptococcal disease; furthermore, patients with AIDS-associated cryptococcal infections now account for 80-90% of all patients with cryptococcosis.Internationally: C neoformans has a worldwide distribution and, similar to in the United States, preferentially infects patients who are immunosuppressed, especially those with AIDS. In sub-Saharan Africa, 15-30% of all patients with AIDS develop cryptococcal disease. However, in some areas, such as Zimbabwe, 88% of patients with AIDS have cryptococcal infection as their AIDS-defining illness. Overall, most case reports of C neoformans var gattii are from Australia, with a few case reports from the southern California coast and tropical regions of Central and South America.
Mortality/Morbidity: Prior to the use of amphotericin B (Throughout this article, the term amphotericin B refers to amphotericin B desoxycholate.), cryptococcal meningitis and disseminated disease invariably were fatal; however, with the availability of amphotericin B, flucytosine, fluconazole, and the azoles, the mortality rate for cryptococcal disease dramatically decreased. In 1995, Speed and Dunt reported a 14% mortality rate in patients with cryptococcal disease who are treated with amphotericin B plus flucytosine and a 28% mortality rate for patients treated with other regimens.Race: No clear racial predilection is reported for either cryptococcal infection or disease. No occupational predilection has been defined.Sex: In most studies, cryptococcal disease reportedly is more common in men than in women.Age: In a 1972 review, Lewis and Rabinovich reported that almost two thirds of patients with cryptococcal disease were older than 40 years; furthermore, in patients aged 50 years and older, cryptococcal disease was more than 3 times as common in men as in women. However, the pandemic of AIDS has lead to a simultaneous and dramatic rise in the incidence of cryptococcal disease and a reduction in the average age of affected patients.
CLINICAL Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous BibliographyHistory: The principal site or sites of infection (ie, pulmonary, CNS, disseminated disease) dictate the medical history of patients with symptomatic cryptococcal disease. Factors that are especially important include the presence of coexisting conditions associated with immunosuppression (eg, steroid use, malignant disease, transplantation) or HIV infection. Other key factors in the history often relate to organ-specific problems (eg, cough, headaches, focal neurological defects, skin rashes).Pulmonary cryptococcosis
The pattern of cryptococcal pulmonary disease is extremely variable, ranging from asymptomatic saprophytic airway colonization to acute respiratory distress syndrome, which is observed in hosts who are immunocompromised (eg, patients with AIDS, organ transplant recipients). On occasion, cryptococcal pulmonary disease may even manifest as a slowly progressive mass that may compress thoracic structures such as the vena cava.
A patient with pulmonary cryptococcosis may present with mild-to-moderate symptoms, including fever, malaise, cough with scant sputum, pleuritic pain, and hemoptysis (rare). More specific and unusual findings include rales or pleural rub. Pleural effusions may be present but are uncommon.
Cavitation and hilar lymphadenopathy are infrequent.
Calcification and pulmonary fibrosis or stranding are usually absent.
Although chronic infection can occur, patients who are immunocompetent usually have spontaneous regression of both clinical and radiological manifestations.
Among patients who are HIV positive and have pulmonary Cryptococcus infection, 5-25% present with cough and dyspnea.
Adult respiratory distress syndrome may ensue.
Pulmonary disease more likely progresses in these patients, requiring antifungal therapy.
Pulmonary disease may occur in the absence of extrapulmonary disease. Conversely, extrapulmonary disease (eg, meningitis) may develop in the absence of identifiable pulmonary pathology.
CNS cryptococcosis
Meningitis and meningoencephalitis are the most common manifestations and are usually subacute or chronic in nature.
This form of infection invariably is fatal without appropriate therapy; death may occur from 2 weeks to several years after the onset of symptoms.
The clinical presentation and course of cryptococcal meningitis are variable, relating in part to underlying medical conditions (eg, diabetes, sarcoidosis, glucocorticoid use) and the immune status of the host.
The most common symptoms are headache and altered mental status, including personality changes, confusion, lethargy, obtundation, and coma.
Nausea and vomiting are frequent; fever and stiff neck are less common.
Some patients who are HIV positive may have minimal or nonspecific symptoms at presentation. Patients are often afebrile or have a mildly elevated temperature.
Symptoms, including blurred vision, photophobia, and diplopia, may occur secondary to arachnoiditis, papilledema, optic nerve neuritis, and chorioretinitis.
Other findings include hearing defects, seizures, ataxia, aphasia, and choreoathetoid movements.
Dementia is a potential sequela and may indicate the presence of hydrocephalus as a late complication.
Cryptococcosis in other sites
After lung and CNS infection, the next most commonly involved organs in disseminated cryptococcosis are the skin, prostate, and medullary cavity of the bones.
Cutaneous manifestations occur in 10-15% of cases and usually take the form of papules, pustules, nodules, ulcers, or draining sinuses.
Umbilicated papules in patients with AIDS may resemble molluscum contagiosum.
Cellulitis with necrotizing vasculitis is reported in patients who undergo organ transplantation.
Bone lesions develop in 5-10% of the patients and are usually osteolytic or resemble cold abscesses. These lesions may be confused with tuberculosis or neoplasm.
Other less common forms of cryptococcosis include the following:
Myocarditis
Chorioretinitis
Hepatitis
Peritonitis
Renal abscess
Prostatitis
Myositis
Adrenal involvement
Prostatic foci may persist after therapy for CNS disease and may act as a reservoir for relapse in men with AIDS.
Physical: The physical findings of patients with cryptococcal infection primarily depend on the patient immune status prior to infection and the site or sites involved. Because the inflammatory responses to encapsulated cryptococci are blunted, extensive involvement of tissues may occur before the patient presents for medical care; furthermore, the limited inflammatory response associated with the encapsulated yeast can result in mild clinical findings.Pulmonary cryptococcosisAlthough C neoformans most often infects patients via the pulmonary route, less than 15% of patients present with a clinical picture of pneumonia. On occasion, isolation of Cryptococcus from sputum may represent colonization rather than true infection.
One third of patients who are immunocompetent and who develop pulmonary infection are asymptomatic or have symptoms so mild that they do not seek medical care.
When symptoms are present in hosts who are immunocompetent, they include cough (54%), cough with the production of scant mucoid sputum (32%), and pleuritic chest pain (46%). Low-grade fever, dyspnea, weight loss, and malaise also may be present.
Night sweats, as observed in tuberculosis, are uncommon in cryptococcal pulmonary disease but may occur with disseminated or CNS disease.
In patients who are immunocompromised and who do not have HIV infection, cryptococcal pulmonary infection is associated with an accelerated course, often with early dissemination. As many as 83% of these patients present with constitutional symptoms (eg, fever, malaise).
Patients co-infected with HIV and Cryptococcus present with fever (84%), cough (63%), dyspnea (50%), headache (41%), and weight loss (47%). Often, patients with co-infection have cryptococcal antigens and cultures that are positive in cerebrospinal fluid (CSF), blood, and urine. Any part of a lung may be involved, and infiltrates may be bilateral, unilateral, multilobar, or lobar.
CNS cryptococcosis
Although C neoformans enters the body via the lungs, the CNS is the main site of clinically evident infection in both immunocompetent and immunocompromised hosts. Following pulmonary infection, cryptococci disseminate widely and may infect any organ. The organs most often involved include the CNS, bones, prostate, eyes, and skin. Prior to the discovery of amphotericin B in 1955, 80% of patients with CNS involvement died within 2 years of diagnosis.
Cryptococcal CNS infections usually involve both the brain and meninges, causing diffuse disease. Immunocompetent hosts may present with either meningitis or focal cryptococcomas. Meningitis manifests with diffuse, nonfocal findings (eg, altered mental status, vomiting), whereas cryptococcomas often manifest with focal neurologic defects.
Cryptococcal skin infection
Approximately 10-15% of patients infected with C neoformans develop skin involvement. In immunocompetent hosts, the skin may be the only site of infection; however, immunosuppressed patients, especially those with AIDS, have skin involvement that must be considered evidence of disseminated disease.
Cutaneous lesions include nodules, ulcers, papules, and vasculitic lesions.
Cryptococcal osteomyelitis
Bone involvement is documented in 5-10% of patients with cryptococcal infection.
Bone lesions are usually osteolytic and may be misinterpreted as neoplastic lesions or osseous tuberculosis.
Other sites of cryptococcal infection
The eyes and prostate are often involved. Eye involvement often manifests as vision loss caused by optic neuritis or endophthalmitis. Rapid diagnosis and treatment are essential in order to preserve the patient's sight.
In men, eradication of cryptococci from the prostate is often difficult; furthermore, the prostate can act as a reservoir for relapse of systemic infections.
Other considerations
A CT scan or MRI in patients with cryptococcal infection may reveal diffuse atrophy or cerebral edema with focal, homogenous, or contrast-enhanced areas. These findings may help distinguish cryptococcal infection from other causes of intracranial mass lesions and infections.
Early cryptococcal meningitis may resemble other mycoses, syphilis, tuberculosis, or meningeal metastases. Do not confuse this condition with chronic meningitis caused by other infections or by noninfectious causes (eg, sarcoidosis, chronic benign lymphocytic meningitis).
Pulmonary findings may be indistinguishable from those of patients with acute pneumonia caused by Pneumocystis carinii, Mycobacterium tuberculous, Histoplasma capsulatum, or other organisms.
Cutaneous lesions are nonspecific and may be mistaken for a large variety of lesions related to other causes, including acne, syphilis, lipoma, tuberculosis, molluscum contagiosum, or basal cell carcinoma.
Bone lesions may be mistaken for tubercular cold abscess or neoplasm.
Causes: Infection with either C neoformans var neoformans or C neoformans var gattii causes cryptococcal disease. The most common pathogen of the genus Cryptococcus in patients who are immunocompromised is C neoformans var neoformans. The most common variety to cause disease in patients who are immunocompetent is C neoformans var gattii.