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Cryptococcus gattii Infections with Cutaneous Involvement

To the Editor: Cryptococcus is an encapsulated basidiomycetous yeast that causes infection in humans through inhalation of basidiospores from the environment. This can subsequently lead to hematogenous spread to lungs, brain, bones, joints, and skin. Although infections typically involve Cryptococcus neoformans in the severely immunocompromised, the recent emergence of Cryptococcus gattii infections in immunocompetent hosts has led to considering the pathogenic role of this pathogen. The outbreak started in 1999 on Vancouver Island, British Columbia, and has spread to the Pacific Northwest. As of 2009, 263 cases have been reported in British Columbia, with Vancouver Island specifically having one of the highest incidences of C. gattii infections worldwide. In British Columbia, there have been 18 reported cases of C. gattii infections involving the skin from 1999 to 2009. In all cases, the patients were systemically unwell. Clinical presentation included pulmonary, neurologic, and skin findings. Biopsy of cutaneous lesions in three cases allowed for tissue diagnosis of C. gattii. We report here the case of a 65-year-old woman with one of the two biopsy-confirmed cases of C. gattii infection involving the skin in British Columbia—the only case that, to the best of our knowledge, first presented to a dermatologist. The patient presented to the private dermatology office of one of the authors (M.S.) in North Vancouver in August 2000 with a skin lesion over the left scapula. The lesion was first noticed by the patient 3 weeks before the visit and had since been slowly growing in size. At the time of assessment, the patient was feeling lethargic and complained of a constant low-grade headache. This woman had traveled to Hornby Island via Vancouver Island in March 2000. Previously, she had been in Parksville, also on Vancouver Island, in late October 1999. Her social history revealed that she was an avid gardener. On examination, the skin lesion clinically appeared as an exophytic red nodule with no secondary changes. No photograph was taken. The differential diagnosis included keratoacanthoma, cutaneous malignancy, cutaneous metastasis, and benign irritated nevus. A skin biopsy was done and showed replacement of the dermis by an acellular mucoid infiltrate containing small budding yeast forms, which were also present in the epidermis (Figure 1 and Figure 2). During systemic workup at a later date, a lumbar puncture cultured C. gattii, confirming the diagnosis of disseminated cryptococcosis. Minimal work has been done to date on the antifungal susceptibility of this cryptococcal species. Given the limited data for specific therapy, our patient was treated according to the 2000 Infectious Diseases Society of America guidelines for disseminated infection with amphotericin B and 5-flucytosine followed by fluconazole for 3 to 12 months. At that time, this guideline was targeted for C. neoformans infections in human immunodeficiency virus (HIV)-positive individuals and has recently been updated to include treatment for the immunocompetent and those with C. gattii infections. This new guideline suggests that treatment of skin infection owing to dissemination should involve combination therapy for at least 6 to 12 months, whereas primary skin infection by direct inoculation may be treated by high-dose fluconazole alone for 6 to 12 months. The disease is well controlled with current guidelines. The patient presented here survived. As in our case presentation, every symptomatic patient should be treated owing to the risk of progression and central nervous system disease. The overall mortality from C. gattii infection from the 218 cases reported between 1999 and 2007 was 8.7%, with the greatest risk in elderly people with central nervous system disease. Given the continual occurrence of C. gattii infection in immunocompetent hosts, it is important for dermatologists to be aware of the possibility of cutaneous involvement or presentation of C. gattii. This diagnosis should specifically be considered in any patient presenting with cutaneous lesions in conjunction with systemic symptoms and a history of residence in or travel to British Columbia or the Pacific Northwest.