The opportunistic mycoses include the infections due to Candida, Aspergillus and zygomycete fungi of the genera Rhizopus, Rhizomucor and Absidia amongst others. Infection affecting the skin is uncommon and these infections seldom present to a dermatologist; any skin involvement has to be set against the background of widespread and life-threatening disease. These infections often occur in patients with severe defects of either neutrophil numbers or function, such as recipients of stem cell transplants and cancer patients. Candida also affects seriously ill patients in intensive care or after abdominal surgery, neonates and after prolonged intravenous feeding. Isolated cases of cutaneous aspergillosis and zygomycosis have been recognised following abrasion at a specific site. Disseminated candidosis rarely affects the skin either in the neutropenic subject or the intravenous drug abuser. Systemic cryptococcus infection has been extensively evaluated in at least 13 randomised controlled trials in people with AIDS.
Patients with deep systemic mycoses rarely present directly to the dermatologist. However, there is an extensive literature on the treatment of disseminated fungal infection and through the involvement of organisations such as the Mycosis Study Group (USA) and the European Organisation for the Research and Treatment of Cancer (EORTC), a number of ground-breaking controlled clinical trials have been undertaken independently, but with the full cooperation, of the pharmaceutical industry. These have focused on various forms of treatment from prevention to specific therapy or empirical therapy.
One form of systemic mycosis that a dermatologist may be called to see is primary cutaneous cryptococcosis. Proving the existence of genuine isolated cutaneous forms of disseminated fungal disease following local trauma and possible direct inoculation compared with localised lesions following bloodstream spread has been difficult, but the concept is important as it has implications for treatment (for example the use of smaller doses that might be effective in localised forms of infection). The problem is well encapsulated by consideration of primary cutaneous cryptococcosis.
Cases of primary cutaneous cryptococcosis are rarely reported and the evidence for direct entry through the skin is often poorly substantiated and generally anecdotal. There are no clinical signs that are likely to provide an accurate indicator that the infection has developed as a result of cutaneous inoculation.35 The evidence for its occurrence therefore can be summarised as follows:
• The first sign of infection is the development of an isolated skin lesion.
• There are no other signs or symptoms of disease, apart from regional lymphadenopathy.
• There is no circulating cryptococcal antigen or antigen in the cerebrospinal fluid measured by conventional tests such as cryptococcal latex antigen test or enzyme-linked immunoabsorbent assay.
• Oral antifungal therapy with fluconazole or itraconazole is effective.
An alternative interpretation for the development of cryptococcal skin lesions was described some time ago by Noble and Fajado36 and was based on the subsequent identification of another focus of infection (for example lung, prostate) and evidence of positive serology in blood or cerebrospinal fluid.37,38 This suggests that many cases of cutaneous cryptococcosis are not primary skin lesions at all but result from fungamia.39,40 In some cases this process produces only a single skin lesion.
Examination of the literature shows that there are some patients who meet the criteria for primary cutaneous cryptococcosis.35 These are generally elderly individuals who do not have any underlying condition known to predispose to cryptococcosis (AIDS, sarcoidosis, T cell lymphoma or chronic oral steroid therapy). Often they give a history of local skin injury, sometimes even associated with a peck of a bird that might be carrying Cryptococcus. Often strains isolated from such lesions belong to C. neoformans serotype D.41 In AIDS patients, cutaneous cryptococcal infections may also be superimposed on some other process such as Kaposi's sarcoma42 and are really part of a disseminated infection.
It is important to emphasise that these are observed criteria and have not, by virtue of the rarity of cutaneous cryptococcosis, been subjected to analysis of sufficient scientific rigour. However, the implications for therapy are sufficiently important that it is recommended that patients who meet the broad criteria for cutaneous cryptococcosis receive treatment with an oral azole antifungal agent, such as fluconazole (at least 200 mg daily) or itraconazole (at least 200 mg daily) until the lesions have resolved, treatment being extended for at least 1 month thereafter. Serology should be monitored again before the end of treatment and for 6 months after the end of treatment. This approach is provided as a guideline based on anecdotal experience and has not been the subject of a clinical trial.
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