Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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Mahreen Ameen and Wanda Sonia Robles
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Mycetomas (Madura foot) are endemic in the tropics and sub-tropics. They are chronic, granulomatous, subcutaneous infections caused by either actinomycetes bacteria or eumycetes fungi, giving rising to actinomycetomas and eumycetomas, respectively. The infectious agents are saprophytes existing in soil or plants, and infection usually results from traumatic inoculation into the skin. Consequently, the disease most commonly affects agriculturalists and those who are bare-foot. The disease is characterized by abscesses, draining sinuses and discharging grains, and it slowly progresses with risks of bone and visceral involvement. The discharging grains represent aggregates of fungal hyphae or bacterial filaments. Actinomycetomas are produced by agents of the genera Nocardia, Actinomadura, Streptomyces and Nocardiopsis. Nocardia is the commonest agent, particularly in the Americas, but Streptomyces somaliensis is more common in Sudan and the Middle East. Eumycetomas are caused by a large number of fungi: Madurella mycetomatis is of particular significance as it is the most prevalent causative agent in regions of India and Africa.
Treatment of mycetomas is generally difficult, and management varies from a very conservative approach to chemotherapy and surgery. Effective chemotherapy is available for actinomycetomas. However, eumycetomas are more refractory to drug therapy.
Eumycetomas may sometimes be managed conservatively as they are usually indolent and seldom life threatening. Treatment is then symptomatic with relief of pain and applications of dressings to affected areas, particularly the sinuses. Any secondary bacterial infection requires treatment. More active management consists of long courses of antifungals, 18–24 months or even longer, together with aggressive surgical excision and debulking. Antifungal therapy is initiated before surgery and continued afterwards to reduce the risk of recurrence. Small lesions have a more favorable prognosis as they are more easily excised completely. Advanced disease with bony involvement characteristically shows poor therapy response, and often requires surgical amputation. Of all the antifungal drugs, azoles have been most commonly used. Fluconazole has been found to be ineffective but ketoconazole and itraconazole have both demonstrated efficacy, particularly at high doses (200–400 mg daily for ketoconazole and 300–400 mg daily for itraconazole). Itraconazole is preferred as it is better tolerated for longer periods of time and is thought to demonstrate greater efficacy than ketoconazole, although there are no published studies comparing their efficacy.
There are reports of the high tolerability and efficacy of the newer broad-spectrum triazoles such as voriconazole and posaconazole against Madurella species and Scedosporium apiospermum infection. This is supported by in vitro susceptibility testing. However, their high costs are prohibitive for use in most endemic regions. Griseofulvin appears to be ineffective. Amphotericin has shown variable responses in the few cases that it has been used in. High-dose terbinafine (500 mg twice daily) has demonstrated limited clinical efficacy that correlates with in vitro susceptibility testing which has shown only moderate efficacy of terbinafine against some black grain mycetomas. In vitro studies have not demonstrated any efficacy of echinocandins against Madurella mycetomatis.
Actinomycetomas are usually amenable to antibiotic therapy, but cure rates vary widely from 60% to 90%. Combined drug therapy is preferred in order to prevent the development of drug resistance as well as to eradicate any residual infection. The duration of drug therapy depends on clinical response. Cure is defined by a lack of clinical activity, absence of grains and negative cultures. Treatment with sulfonamides and sulfonamide combinations such as trimethoprim–sulfamethoxazole (co-trimoxazole) are usually first line. Aminoglycosides, tetracyclines, rifampicin, ciprofloxacin and amoxicillin-clavulanate have also been successfully used. Parenteral amikacin and oral co-trimoxazole combination therapy is especially advocated for cases at risk of bone or visceral involvement. Actinomycetomas seldom require surgical management.
Direct microscopy
Culture
Histopathology
It is imperative to differentiate between eumycetomas, which respond poorly to chemotherapy, and actinomycetomas, which generally respond well. Furthermore, species identification is important as it has treatment and prognostic implications, some species having demonstrated higher efficacy to some chemotherapy regimens than others.
The clinical diagnosis can be confirmed by the demonstration and identification of grains, which can be obtained by direct extraction, fine needle aspiration, or deep tissue biopsy. Direct microscopy of a crushed grain in 20% potassium hydroxide gives an indication of the size and shape of the grain, which provides an initial clue to the causative agent, whether bacterial or fungal. Histopathology of a deep surgical biopsy demonstrates a granulomatous, inflammatory reaction with abscesses containing grains. Culture of grains using Sabouraud or blood agar media permits species identification. However, fungal culture can be particularly difficult, as morphological differentiation of fungi may be poor or delayed. Molecular tests have therefore been developed for species identification of several black-grained eumycetomas, including species-specific polymerase chain reaction (PCR) analysis. Serological tests such as enzyme-linked immunosorbent assay (ELISA) are employed by some centers to support diagnosis as well as to assess therapy response. Radiology and ultrasound enable assessment of disease extent and bony involvement. Helical computed tomography can provide detailed assessments of soft tissue and visceral involvement.
Fahal AH. Trans R Soc Trop Med Hyg 2004; 98: 3–11.
A review article based on the experiences of the Mycetoma Research Centre in Sudan. Combined antibiotic treatment for actinomycetomas and aggressive surgery in combination with antifungals for eumycetomas is recommended.
Ahmed AO, van Leeuwen W, Fahal A, van de Sande W, Verbrugh H, van Belkum A. Lancet Infect Dis 2004; 4: 566–74.
A good review article on developments in the clinical, epidemiological and diagnostic management of Madurella mycetomatis eumycetoma.
Welsh O, Vera-Cabrera L, Salinas-Carmona MC. Dermatol Clin 2007; 25(2): 195–202.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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