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Therapeutics in Dermatology
A reference textbook in dermatology

Mycetomas

6 June 2012, by DEVELOUX M.

Mycetomas are pathological processes in which exogenic fungal or actinomycosic etiologic agents produce parasite grains. This definition excludes true endogenic Actinomyces israeii actinomycosis.

Mycetomas are infections arising in semi-arid tropical regions. The main endemic areas are Mexico, Africa on either side of the 15th parallel north, the Middle East and India. While most cases in Europe are observed in immigrants from endemic regions, a limited number have been reported in indigenous Europeans. Actinomycosis infections are more prevalent than fungal mycetomas.

The infectious agents live in saprophytes in the soil and plants (thorny). They enter the body through cuts and scratches, which explains the prevalence of the diseases in rural areas. More men than women are affected and the incidence is higher in the 20 to 40 age group.

The typical forms are easy to diagnose. In more than 70 percent of cases, a single lesion is present on the foot. The clinical appearance is suggestive of a fistular tumour ("Madura foot"). The fistulas weep pus containing grains that are often visible to the naked eye. The main differential diagnoses are Kaposi’s disease, tuberculosis, oesteomyelitis or another severe fungal infection.

The diagnosis is confirmed by the direct examination of the grains and/or pus, cultures and histology. The colour of the grains is very important: black grains are always fungal (Madurella mycetomatis, Leptosphaeria senegalensis), red are always from actinomyces (Actinomadura pelletieri) and white and yellow grains can be either fungal (Pseudallecheria boydi) or actinomycosic (Nocardia sp, Actinomadura madurae).

This disease has a chronic course lasting several years and causing, in the long run, various complications, the most severe of which involve the bone. At this stage, it becomes extremely debilitating.

1 - MONITORING STRATEGY

Before starting treatment, disease staging is fundamental and must include a radiological workup. The new medical imaging techniques (CT and MRI) clearly show the tumour margins. These same techniques can be used to assess the outcomes of treatment during therapy.

2 - TREATMENT OPTIONS

Mycetomas, particularly the fungal type for which no satisfactory medical options are available, are difficult to treat. The treatments offered for fungal mycetomas are radically different to those for actinomycosis.

Fungal mycetomas require an initial antifungal treatment but this is rarely sufficient to achieve a cure and surgery is frequently required afterwards. Numerous antifungal agents have been used in the treatment of fungal mycetomas with varying degrees of success. Some azole compounds have shown efficacy in vitro but this is not always followed by a corresponding efficacy in vivo. The only promising results (cure or improvement) have been obtained with itraconazole. Some cases have been successfully treated with voriconazole and posaconazole, but their efficacy requires further confirmation. The response appears to be better when the fungal mycetoma is of the white grain type.

The first-line treatment for actinomycosis is always medicinal. The current gold standard is cotrimoxazole. If a patient does not respond, or responds poorly to the standard treatment, a group of Mexican authors has suggested combining cotrimoxazole with courses of amikacine. Amoxicillin-clavulanic acid is another option but the successful outcomes were obtained with Nocardia sp mycetomas and no data are available concerning its effects on other species causing actinomycosis. Other molecules are currently being evaluated.

3 - TREATMENT STRATEGY

In the case of fungal mycetomas, a medical treatment should be given first. In endemic countries, this is limited by the cost of azole drugs which are required for long periods of time. Treatment lasts for 6 months to 2 years and even more. Authors from the Sudan presented a series of 13 cases treated with itraconazole for 3 months at a dose of 400 mg/day and then dropped to 200 mg/day for the following 9 months. One cure was obtained with the medical treatment but in other cases it also led to encapsulation of the grains making surgery easier and less mutilating and decreasing the risk of recurrence. Some patients have been cured with voriconazole and posaconazole but treatment failures have also been reported. It is difficult to draw any conclusions in the absence of randomized trials. Most authors agree on the need for medical treatment followed by surgery. The aim is to preserve the patient’s physical function but employ sufficiently wide surgical margins to prevent secondary recurrence of the tumour. In endemic areas, late diagnosis of the condition and difficulties in obtaining anti-fungal medications mean that amputation is all too often the only option. If only the toes or parts of the toes are involved, then a limited amputation is possible. In the more extensive forms, major and proximal amputation may be required. Wherever possible, the amputation should leave a stump on which the patient may place weight.

The first-line treatment for actinomycosis is always medical although exceptions have been reported (historic cases). Immediate surgical removal of the lesion, especially when the granules are small, is believed to promote lymph node metastases and distant involvement. The treatment currently recommended is cotrimoxazole for a minimum of one year. Treatment can be pursued if the patient is not cured after this time. If a patient does not respond or responds poorly, a group of Mexican authors has suggested combining cotrimoxazole with courses of amikacine. One course consists of amikacin (15 mg/kg/day) for three weeks and cotrimoxazole (7 to 35 mg/kg/day) for five weeks. Several courses, up to a maximum of 4, may be required.

It is very difficult to confirm that a mycetoma has been cured after withdrawal of an apparently clinically effective treatment. As the disease has a torpid course, recurrence of the infectious processes has been observed some time after an apparent cure. Patients must therefore undergo regular clinical examinations for several years. Recurrence is more common with fungal mycetomas.

Prevention of mycetomas consists in the immediate treatment of wounds liable to become infected and encouraging people living in endemic zones to wear shoes at all times. However, this is impossible to enforce. A positive outcome is dependent on the prompt detection of the disease.

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