Chromoblastomycosis

Published on 18/03/2015 by admin

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Chromoblastomycosis

Wanda Sonia Robles and Mahreen Ameen

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Chromoblastomycosis is a chronic fungal infection of cutaneous and subcutaneous tissues endemic in Central and South America, Africa, Australia, and Japan. It is caused by the traumatic implantation of pigmented (dematiaceous) fungi, which produce characteristic thick-walled sclerotic bodies (also known as muriform or Medlar bodies) in infected tissues. The commonest etiological agents are Fonsecaea pedrosoi, Phialophora verrucosa and Cladophialophora carrionii. Clinically, chromoblastomycosis presents as plaques, nodules or warty, exophytic lesions, which most commonly affect the feet and lower legs. Lesions are slow growing, and over years extend centripetally leaving central areas of scarring. Disease is usually localized but can spread through autoinoculation or lymphatic dissemination, producing metastatic lesions away from the primary site. Complications include ulceration, secondary bacterial infection, and lymphedema. Rarely, malignant transformation (squamous cell carcinoma) in chronic lesions and systemic involvement have been reported.

Management strategy

Chromoblastomycosis is a difficult-to-treat deep mycosis that is characterized by low cure rates and high rates of relapse, particularly in chronic and extensive disease. Studies report highly variable rates of clinical and mycological cure, ranging from 15% to 80%. The choice of treatment and outcome depends on the etiological agent, the extent of the lesions, clinical topography, and the presence of complications (dermal fibrosis and edema may reduce tissue antifungal drug levels). F. pedrosoi is the most common etiological agent, but has the lowest sensitivity to the major systemic antifungal agents. C. carrionii and P. verrucosa are much more sensitive and have been found to respond more favorably to treatment.

Surgical excision may be successful for small and localized lesions. It is performed with wide surgical margins and is usually accompanied by chemotherapy in order to reduce the risk of recurrence. Curettage and electrodesiccation is not recommended because it may promote lymphatic spread. Other physical modalities include cryosurgery using liquid nitrogen, and thermotherapy (applying local heat to produce controlled temperatures ranging from 42°C to 45°C, that inhibit fungal growth) using a variety of methods including benzene pocket warmers and pocket handkerchief type warmers. Cryosurgery and thermotherapy have the advantage that they are relatively inexpensive treatment options.

There are no comparative trials of antifungal chemotherapy for chromoblastomycosis. Itraconazole (100–400 mg daily) and terbinafine (250–500 mg daily) are considered first-line treatments, both drugs having shown high in vitro activity against the causative agents of chromoblastomycosis. They are typically given for long periods of time at high doses. Dual therapy with itraconazole and terbinafine is recommended if it is affordable and tolerated. It is not uncommon for more than one treatment modality to be used, such as oral antifungals combined with surgery, cryotherapy or thermotherapy. For example, itraconazole and/or terbinafine combined with cryosurgery is advocated for extensive disease. The antifungal is given first until there is a maximum reduction in lesion size, which usually requires 6 to 12 months of chemotherapy. The lesions then require several treatments with cryosurgery.

Of the other antifungal agents, ketoconazole is not recommended for treating chromoblastomycosis as it cannot be given at high doses for long treatment periods because of its toxicity profile. Despite a few cases in the early literature reporting successful treatment with fluconazole, it too is not recommended as in vitro studies have shown that it has little activity against black fungi. Flucytosine (converted into 5-fluorouracil in fungal cells) was an early treatment that demonstrated some degree of efficacy. It is associated with a high risk of developing resistance but this can be overcome if it is used in combination with another antifungal. It is also hepatotoxic and myelotoxic, requiring regular monitoring of serum levels. With the emergence of newer antifungals it is rarely used now except for resistant cases. Amphotericin B monotherapy is ineffective, and even in combination with other antifungals results are generally poor. However, amphotericin B and flucytosine dual therapy has demonstrated efficacy, in vitro studies having demonstrated synergistic activity between the two drugs. The new, second generation triazoles such as posaconazole and voriconazole are promising drugs in the management of deep cutaneous mycoses, but experience to date is limited by their prohibitively high costs in endemic settings.

Specific investigations

A positive direct examination of scrapings in 10% potassium hydroxide will demonstrate the thick-walled, brown sclerotic cells that are pathognomonic of chromoblastomycosis, irrespective of the causative species. Specimens are more likely to yield a positive result if they include the ‘black dots’ visible on the surface of the lesion. Culture enables the identification of the causative agent. It is a slow-growing fungus and culture may be inconclusive due to poor morphological differentiation. Polymerase chain reaction (PCR) has been developed for the identification of Fonsecaea and C. carrionii. Serological tests such as ELISA can be useful in evaluating therapy response, but like PCR it is not widely available in most endemic settings. A biopsy demonstrates the typical sclerotic bodies in a granulomatous lesion with transepithelial elimination.

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