Mycetoma is a chronic granulomatous infection that is present worldwide and endemic in tropical and subtropical regions. The infection is caused by the traumatic inoculation of a fungus (eumycetoma) or a bacterium (actinomycetoma) and generally remains localized, causing cutaneous and subcutaneous tissue swelling, nodule formation, and drainage through sinus tracts.
The organisms causing mycetoma aggregate into grains or sclerotia and are found in the discharge. Without treatment, this disease may lead to severe local tissue destruction, requiring surgical amputation.
The most common cause of mycetoma worldwide is eumycetes, particularly Madurella mycetomatis, which causes >70% of cases in certain regions of Central Africa, including Sudan. Mycetoma is especially endemic and severely debilitating in Sudan, where Abbott reported 1231 cases occurring over a 2.5-year period. Interestingly, the predominant source also varies by region. For example, in Central America and Mexico, mycetoma is more commonly caused by the actinomycetes Nocardia brasiliensis, Streptomyces somaliensis, Actinomadura madurae, and A. pelletierii. In the US, mycetoma is most commonly caused by the fungus Pseudallescheria boydii.
The characteristic clinical triad for mycetoma is swollen tissue, draining sinuses, and identification of grains from the discharge. Inoculation is followed by development of a painless subcutaneous nodule that spreads slowly. Usually, this nodule is round and firm, but it may also be soft, lobulated or, rarely, cystic. As the nodule increases in size, secondary nodules and papules may develop with accompanying sinuses that drain serous, serosanguineous, or purulent discharge. Over time, some of the sinuses close and heal, while new ones form.
The overlying skin may be shiny with local hyperhidrosis and is usually hyperpigmented but may also be hypopigmented. Abscesses occur under the surface of the skin and as the disease progresses, the lesions extend into bony tissue, causing small cavities (2–10mm) to develop. If untreated, bony involvement can be extensive and devastating, leading to complete bone destruction. Much later and more rarely in the disease, lesions may affect nerves and tendons. Local lymphadenopathy is common with small and shotty lymph nodes, and may result from secondary bacterial infection, spread of mycetoma, or immune complex deposition as part of the local immune response to infection. Chronic infection may lead to disability, distortion, and deformity, and may be fatal if untreated.
Mycetoma is typically unilateral, and most often (≈70–80%) the foot is the primary site of infection, followed by the hands (≈12%), legs, and knee joints. Individuals infected with actinomycetes exhibit a more rapid, progressive clinical disease with increased inflammation, local destruction, and quicker bone invasion compared with those infected with eumycetes, who have well-defined, slower growing lesions that stay encapsulated longer.
The differential diagnosis of mycetoma includes soft tissue tumors such as lipoma, fibroma, fibrolipoma, sarcomas, and malignant melanoma, as well as chronic osteomyelitis. Further considerations include tuberculosis, Kaposi sarcoma, and other subcutaneous mycoses such as sporotrichosis and chromoblastomycosis diagnosis A variety of modalities exist to diagnose mycetoma, the most definite of which is to obtain a sample of discharge and visualize its grains
Use of a variety of stains, including 20% potassium hydroxide, acid-Schiff, or Grocott’s methenamine silver, allows visualization of grains and fungal and actinomycete filaments. Actinomycetes are usually observed with granules ≈100μm in diameter and delicate, branched filaments about 1μm in diameter; eumycetes are usually seen as a mass of hyphae embedded in intercellular cement with filaments wider than 1μm.
Individuals infected with eumycetes require both medical and surgical intervention. First-line medical management recommendations from the Mycetoma Research Center at the University of Khartoum (Khartoum, Sudan) are either ketoconazole 400–800mg daily or itraconazole 400mg daily. Cure rates with ketoconazole seem to be dose dependent, with some individuals requiring treatment for months or years. Use of itraconazole has been associated with good clinical response with low recurrence rates. With both medications, liver function tests should be monitored before and during treatment, as both may be hepatotoxic.
Medical management of eumycetes is discontinued with clinical, serologic, radiologic, and ultrasonic cure.
Surgery is often also performed as a first-line treatment for eumycetes. Care must be taken throughout any surgical procedure to prevent contamination and further infection, with emphasis placed on maintaining the integrity of the capsule. Aggressive wide excision should be performed for early localized lesions and debulking surgery for extensive disease with bony involvement. Chemotherapy must accompany any debulking surgery. Amputation may be necessary in advanced disease or for resistant organisms. Following completion of surgery, flooding of the wound with iodine is recommended to eliminate any residual fungi.
Unlike eumycetes, infections caused by actinomycetes have a better response to medical management with antibacterials and other chemotherapeutics. A variety of combinations have been employed to combat actinomycetes infections. In 1976, Mahgoub described the efficacy of trimethoprim/sulfamethoxazole (cotrimoxazole), dapsone, streptomycin, sulfadoxine/pyrimethamine and rifampin (rifampicin). The most common starting regimen consists of streptomycin (14 mg/kg daily) intramuscularly for 4 weeks, which is then given on alternate days with dapsone (1.5 mg/kg twice daily). If this regimen fails, dapsone is replaced by trimethoprim/sulfamethoxazole (14 mg/kg twice daily) or rifampicin (15–20 mg/kg daily). Drug resistance among these organisms is high and best combatted with combined drug therapy. The reported cure rate for these infections is 60–90%, with the mean duration of treatment being >1 year.
Other medications that have been used with efficacy against certain actinomycetes include amikacin, imipenem, and amoxicillin/clavulanic acid. Ramam et al. described the efficacy of a two-step regimen. Patients were initially placed on penicillin, gentamicin, and trimethoprim/sulfamethoxazole, then switched to maintenance treatment with amoxicillin and trimethoprim/sulfamethoxazole.
Surgery is indicated for individuals whose infections are resistant to medical treatment or bony involvement that will not respond to continual long-term conservative treatment. These procedures require removal of a margin of healthy tissue because actinomycetoma has an ill-defined border.
Lichon V., Khachemoune, Mycetoma, A Review. A. Am J Clin Dermatol 2006; 7 (5): 315-321