Cryptococcosis is the infection caused by the encapsulated yeast Cryptococcus neoformans, a dimorphic fungus. It was first demonstrated by Busse and Buschke in 1894. Although the primary site of infection is most often the lungs, the disease frequently manifests with signs of extrapulmonary dissemination, involving the skin in approximately 10-15% of cases. Cryptococcus has a worldwide distribution. It has been recovered from pigeon excreta and from other wild and pet birds, soil, dust, and human skin.
The two variants of C neoformans are neoformans (serotypes A [most common in the United States] and D) and gattii (serotypes B and C). Strains of serotype D are more likely to be found in skin lesions. Either variant can cause disease, although more reported cases involve the neoformans variant. C neoformans var. gattii is associated with the Eucalyptus camaldulensis tree native to Australia. Infections with the neoformans variant are thought to be more common in immunocompromised patients, while infections with the gattii variant are more common in immunocompetent individuals. Infections can range from mild symptoms such as fever and cough to severe disseminated disease resulting in death. Host immune factors, in particular cell-mediated immunity, are the primary determinant of outcome.
Infection most commonly begins in the lungs after inhalation of the airborne yeast, and it may remain localized in 90% of cases. Manifestations of the disease depend on the host response, inoculum size, and innate virulence of the organism. Primary cutaneous infection may result from direct inoculation of organisms into the skin by an infected object; however, this is rare. Cutaneous Cryptococcus infection should be presumed to be disseminated until proven otherwise, and a search for other sites of involvement must be immediately undertaken.
Disseminated disease results after hematogenous spread, with the CNS and skin being the most common secondary sites. In addition to meningitis, disseminated Cryptococcus infection can cause hepatitis, osteomyelitis, prostatitis, pyelonephritis, and peritonitis. Cutaneous signs may be the first indication of infection, preceding the diagnosis of disseminated disease by 2-8 months, making its recognition crucial to early treatment.
Dissemination occurs primarily in immunocompromised hosts, such as those with AIDS, lymphoreticular malignancy (eg, chronic lymphocytic leukemia), sarcoidosis, or systemic lupus erythematosus or those on long-term immunosuppression or prednisone therapy for organ transplantation or connective-tissue disease. In HIV-infected patients, Cryptococcus infection is typically seen when the CD4 count is less than 50-100 cells/µL and is an AIDS-defining illness. In a study of 40 HIV-negative patients with Cryptococcus infection, 65% had an associated underlying condition. Of these, 41% were on immunosuppressive drug treatment, 16% had systemic lupus erythematosus, 16% had malignancy, and 14% had diabetes mellitus.
Cryptococcal infection can be associated with Hodgkin lymphoma. 
The prevalence in AIDS patients ranges from 3-6%. The prevalence in organ transplantation patients reportedly is 2.8%, which makes it the third most common invasive fungal infection.
The prevalence varies greatly in AIDS patients, from 3% in the United Kingdom to greater than 12% in parts of Africa. Cases of cryptococcosis without meningeal involvement have been reported in HIV-positive patients in Africa. 
Lizarazo et al  published the results of a national survey on cryptococcosis in Colombia, based on survey data recorded over a 9-year period from 1997-2005. From 76 centers, 931 surveys were received (82.7% were males, 17.3% were females). In the data, 59.4% of respondents were aged 20-39 years, and 25 children younger than 16 years were included. Of the respondents, 78.1% had HIV infection. The mean annual incidence rate of cryptococcosis in the general population was 1 case in 2.4 million inhabitants, but in the AIDS patients, the rate was 1 case in 3000 persons.
The associated disease syndromes were as follows:
Neurocryptococcosis - 891 cases (95.7%)
Pulmonary disease - 27 cases (2.9%)
Cutaneous lesions - 5 cases (0.5%)
Ganglionar forms - 2 cases (0.2%)
Oropharyngeal lesions - 2 cases (0.2%)
Peritonitis - 1 case (0.1%)
Liver lesion - 1 case (0.1%)
Cellulitis - 1 case (0.1%)
Urinary tract infection - 1 case (0.1%)
The most frequent clinical features were as follows:
Nausea and vomiting (59.1%)
Mental status changes (46.2%)
Meningeal signs (33.4%)
Visual alterations or loss of vision (20.9%)
Laboratory data showed that direct examination of cerebrospinal fluid revealed a positive result in 92.8% cases and Cryptococcus was recovered in 90.3% of the cases. Cryptococcal antigen reactivity was 98.9% in cerebrospinal fluid and 93.7% in serum samples. From 788 isolates submitted, 95.9% were Cryptococcus neoformans var. grubii serotype A, 0.3% were C neoformans var. neoformans serotype D, 3.3% were C neoformans var. gattii serotype B, and 0.5% were C neoformans var. gattii serotype C.
In a Brazilian report of 2 general hospitals between 2005 and 2010, 11 patients were noted to have cryptococcus,  81.8% of which were male. Researchers identified immunosuppression in 54.5% of patients, and all of them were taking corticosteroids for a variety of diseases. All patients had lesions, most with an infiltrative or tumoral aspect on the upper limbs. Fluconazole dosed up to 400 mg was effective treatment.
All races are equally affected.
For disseminated disease, the reported male-to-female ratio is 3:1. For primary cutaneous Cryptococcus infection, the male-to-female ratio is 1:1.
Cryptococcus infection is most common in persons aged 30-60 years. Cryptococcus laurentii is a very rare human pathogen, but was noted in an immunocompetent 8-year-old child.  It occurred on the forearms and was successfully treated with fluconazole.
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