Cutaneous Cryptococcus

Updated: Nov 18, 2019
  • Author: Aziz Khan, MD, MBBS; Chief Editor: Dirk M Elston, MD  more...
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Cryptococcosis is an infection caused by the encapsulated yeast Cryptococcus neoformans and Cryptococcus gattii. It was first demonstrated by Busse and Buschke in 1894. Although the primary site of infection is most often the lungs, with strong tropism for the central nervous system, the disease frequently manifests with signs of extrapulmonary dissemination, involving the skin in approximately 10-15% of cases. C neoformans has a worldwide distribution, while C gattii is endemic to temperate, tropical, and subtropical climates. C neoformans is found worldwide in soil in association with bird excreta, especially pigeons, and from other wild and pet birds. C gattii is associated with the Eucalyptus camaldulensis tree native to Australia and has traditionally been identified in tropical and subtropical regions. However, it has also been associated with temperate climates. as well. [1, 2, 3, 4, 5]

Cryptococcus is classified into four serotypes, A, B, C or D. Serotype A and D were previously classified under the species C neoformans; however, serotype A has been proposed to be reclassified into a separate variety Cryptococcus neoformans var grubii. [6] Serotype B and C are classified as a separate species, C gattii. 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. 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, Hodgkin lymphoma [7] ), sarcoidosis, systemic lupus erythematosus, those on long-term immunosuppression or prednisone therapy for organ transplantation or connective-tissue disease. [8, 9, 10] 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.



Cryptococcus infection occurs primarily from the inhalation of infectious yeast from contaminated soil. Primary cutaneous infections occur through direct inoculation via trauma, while secondary cutaneous infection occurs through hematogenous spread. C neoformans is found worldwide in soil contaminated with bird excreta, especially pigeons and from other wild and pet birds.C gattii is associated with the E camaldulensis tree native to Australia and has traditionally been identified in tropical and subtropical regions. However, it has also been associated with temperate climates. [1, 2, 3, 4, 5] Immunosuppression (eg, HIV infection, leukemia/lymphoma, sarcoidosis, long-term immunosuppression or prednisone therapy for organ transplantation or connective-tissue disease) is a key factor in developing disseminated disease.




United States

The incidence of Cryptococcus infection was reported to be very low prior to the AIDS epidemic (0.8 case per million population). However, in 1992, at the height of the AIDS epidemic, the incidence increased to 5 cases per 100,000 population. Since the use of antiretroviral therapy, the incidence has decreased to very low levels. [11]

Studies have reported an overall prevalence of 2.9% in patients with AIDS, based on cryptococcal antigen positivity. A CD4 count of 50 cells/µL or less was associated with an increased prevalence of cryptococcal antigen positivity. [12]


The burden of cryptococcal infection remains very high in sub-Saharan Africa. The prevalence varies greatly in AIDS patients, from 3% in the United Kingdom to greater than 12% in parts of Africa. [1, 13] Cases of cryptococcosis without meningeal involvement have been reported in HIV-positive patients in Africa. [14]

Lizarazo et al [15] 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:

  • Headache (85.2%)

  • Nausea and vomiting (59.1%)

  • Fever (59%)

  • Mental status changes (46.2%)

  • Meningeal signs (33.4%)

  • Cough (23.6%)

  • 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 C neoformans var grubii serotype A, 0.3% were C neoformans var neoformans serotype D, 3.3% were C gattii serotype B, and 0.5% were C gattii serotype C.

In a Brazilian report of two general hospitals between 2005 and 2010, 11 patients were noted to have cryptococcus, [16] 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 races are equally affected.


For disseminated disease, the reported male-to-female ratio is 3:1. For primary cutaneous cryptococcosis in immunocompetent patients, the reported male to female ratio is 17:4. [17]


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. [18] It occurred on the forearms and was successfully treated with fluconazole.



Primary cutaneous cryptococcosis in immunocompetent patients carries an excellent prognosis, with a cure rate of around 95% with adequate medical therapy. [17]

Lifelong treatment and surveillance may be required for immunosuppressed patients.

Untreated disseminated Cryptococcus infection has a mortality rate of nearly 100%.