Introduction
Background
Mycetoma is a chronic, granulomatous disease of the skin and subcutaneous tissue, which sometimes involves muscle, bones, and neighboring organs. It is characterized by tumefaction, abscess formation, and fistulae. It typically affects the lower extremities, but it can occur in almost any region of the body. Mycetoma predominately occurs in farm workers, but it can also occur in the general population.1
Gill first described the disease in the Madura district of India in 1842, hence the term Madura foot. In 1860, Carter named the condition mycetoma, describing its fungal etiology. In 1813, Pinoy described the mycetoma produced by aerobic bacteria that belong to the actinomycete group and classified mycetomas as those produced by true fungi (eumycetoma) versus those due to aerobic bacteria (actinomycetoma). Both types have similar clinical findings.
Also see the eMedicine Infectious Diseases article Mycetoma.
Pathophysiology
Mycetoma is produced by the introduction of microorganisms (bacteria or fungi) via localized trauma of the skin with thorns, wood splinters, or implantation with solid objects. Clinically, the disease begins as small, firm nodules that can persist (mini-mycetomas) or evolve to form extensive suppurative plaques measuring up to 20 cm in diameter. Eumycetomas tend to be more localized than actinomycetomas.
In experimentally induced Nocardia brasiliensis actinomycetomas in mice, production of granules (or "grains") containing the bacterium can be observed 15 days after inoculation. The grains are surrounded by polymorphonuclear cells (PMNs), lymphocytes, plasma cells, and histiocytes. Murine infection can evolve into a chronic disease similar to the clinical manifestations observed in humans. Severe inflammation and deformity, abscesses, ulcers, and fistulae are present 28 days after infection.
The in situ production of cytokines in the microabscesses has been reported in the murine infection. Tumor necrosis factor-alpha is produced in the first days of infection, decreasing later to nondetectable quantities at day 90. Interleukin (IL) – 1beta, interferon gamma, transforming growth factor-beta, IL-10, IL-4, and IL-6 are produced constantly during the 90 days, but IL-6 is the only one with a significant increase once the mycetoma is fully established (90 d).2
The host immune response in humans and mice involves the production of high levels of anti– N brasiliensis immunoglobulin G antibodies. Quantitation of these antibodies is important for diagnosis. Immunoglobulin M anti– N brasiliensis antibodies can protect mice from an experimental infection.3 Activation of cellular immunity and production of cytokines are involved in resistance and elimination of the N brasiliensis bacterial cells.
Frequency
United States
Mycetoma occasionally occurs in the United States, particularly in the South.
International
Mycetoma is endemic around the Tropic of Cancer, 15° south and 30° north of the equator, in tropical, subtropical, and temperate regions. Mexico, Venezuela, Sudan, India, Pakistan, Senegal, and Somalia have the highest incidences of this disease worldwide. The United States, Asia, and other Latin American countries have reported cases less frequently.
The most common agents isolated in African countries are Madurella mycetomatis, Streptomyces somaliensis, and Actinomadura pelletieri. In Mexico, which shares common climatic conditions with the African countries, most of the cases are found in rural areas. In Mexico, 98% of cases of mycetoma are caused by actinomycetes, mainly N brasiliensis (86%) and Actinomadura madurae (about 8%).4 In another high frequency area, India, 65% of cases are produced by actinomycetes and the rest by eumycetes, mostly M mycetomatis.
Worldwide, approximately 60% of cases of mycetomas are of actinomycotic origin.
Mortality/Morbidity
Mycetoma is usually painless; individuals who are affected seek medical attention mainly because of the tumefaction and draining sinuses. In the rare cases affecting the thorax or the head, mycetoma can be fatal because of the spread of microorganisms to adjacent organs. Rarely, the disease can spread by hematogenous dissemination (Nocardia asteroides and N brasiliensis).
Sex
Mycetoma is more common in men than in women. The male-to-female ratio is 3:1.
Clinical
History
- Mycetoma occurs most commonly in people who work in rural areas where they are exposed to acacia trees or cactus thorns containing the etiologic agents that normally live as saprobes. However, the disease has also been found in individuals who work in the city in various occupations.
- If left untreated, mycetoma can affect the underlying bones, joints, or adjacent organs.
Physical
- Examination typically reveals painless tumefaction of the affected area.
- The skin is usually darker and firmer than the surrounding areas.
- Nodules, abscesses, and fistulae draining a clear viscous or purulent exudate can be observed.
- Granules of the microorganisms may occasionally be seen with the naked eye, as in the case of mycetoma caused by A madurae and M mycetomatis among others.
- The most common anatomical locations affected by this disease are the upper and lower limbs, particularly the feet and the lower legs. In Mexico, the next most commonly affected site is the thoracic area, but this varies from country to country. Rarely, mycetoma can also be observed on the buttocks, the groin area, the head, and the neck.
Actinomycetoma of the foot (left) and arm (center) caused by Nocardia brasiliensis. Multiple nodules and fistulae are present. Microscopic examination of the pus (right). The granules are multilobulated and are surrounded by abundant clubs.
Eumycetoma. Mycetoma of the hand (left). Microscopic features of a Madurella mycetomatis grain are observed (center). Notice the presence of brownish hyphae and intercellular cement (hematoxylin and eosin stain). Macrocolony of another eumycotic agent, Pseudallescheria boydii (right).
Causes
Eumycetomas can be produced by a variety of fungi (see Table 1); however, actinomycetomas are mainly produced by bacteria of 4 genera: Nocardia, Actinomadura, Streptomyces, and Nocardiopsis (see Table 2), the last of which is rarely found.
Although traditionally it has been considered that mycetoma is produced by the pathogenic properties of the causative agents, recently it has been observed that genetic polymorphisms involved in neutrophil function are related to either the production of human mycetoma or its size, in the case of M mycetomatis infection. IL-8 (CXCL8), its receptor CXCR2, thrombospondin-4, nitric oxide synthase, and complement receptor 1 have significant differences in mycetoma patients compared with geographically and ethnically matched controls. These findings open the possibility that certain individuals are predisposed to this infection.5
Table 1. Fungi Causing MycetomaOpen table in new window
Table
White grain | Black grain |
Acremonium falciforme | Exophiala jeanselmei |
Acremonium kiliense | Madurella grisea |
Acremonium recifei | M mycetomatis |
Cylindrocarpon destructans | Leptosphaeria tomkinsii |
Fusarium moniliforme | Leptosphaeria senegalensis |
Fusarium solani | Pyrenochaeta mackinnonii |
Neotestudina rosatii | Pyrenochaeta romeroi |
Pseudallescheria boydii | Phlenodomus avramii |
White grain | Black grain |
Acremonium falciforme | Exophiala jeanselmei |
Acremonium kiliense | Madurella grisea |
Acremonium recifei | M mycetomatis |
Cylindrocarpon destructans | Leptosphaeria tomkinsii |
Fusarium moniliforme | Leptosphaeria senegalensis |
Fusarium solani | Pyrenochaeta mackinnonii |
Neotestudina rosatii | Pyrenochaeta romeroi |
Pseudallescheria boydii | Phlenodomus avramii |
Table 2. Microorganisms Causing Actinomycetomas in Humans
Open table in new window
Table
Etiologic agent | Grain |
A madurae | White, large, 1-5 mm in diameter |
A pelletieri | Red, hard, 1 mm in diameter |
N brasiliensis | White to yellow, multilobed, soft, <0.5 mm in diameter |
N asteroides | Uncommon, white, soft, <0.5 mm in diameter |
Nocardia otitidiscaviarum | White to yellow, lobed, <0.5 mm in diameter |
Nocardia transvalensis | White to yellow, <0.5 mm in diameter |
Nocardia veterana 6 | -- |
Nocardia mexicana 7 | -- |
Nocardiopsis dassonvillei | White to yellow, <0.5 mm in diameter |
S somaliensis | Yellow, hard, 2 mm in diameter |
Streptomyces sudanensis | Yellow, hard, 2 mm in diameter |
Etiologic agent | Grain |
A madurae | White, large, 1-5 mm in diameter |
A pelletieri | Red, hard, 1 mm in diameter |
N brasiliensis | White to yellow, multilobed, soft, <0.5 mm in diameter |
N asteroides | Uncommon, white, soft, <0.5 mm in diameter |
Nocardia otitidiscaviarum | White to yellow, lobed, <0.5 mm in diameter |
Nocardia transvalensis | White to yellow, <0.5 mm in diameter |
Nocardia veterana 6 | -- |
Nocardia mexicana 7 | -- |
Nocardiopsis dassonvillei | White to yellow, <0.5 mm in diameter |
S somaliensis | Yellow, hard, 2 mm in diameter |
Streptomyces sudanensis | Yellow, hard, 2 mm in diameter |
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References
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Further Reading
Keywords
mycetoma, Madura foot, maduromycosis, actinomycetoma, eumycetoma, Nocardia species, Actinomadura species, Streptomyces species, Nocardiopsis species, Nocardia brasiliensis, N brasiliensis, Actinomadura madurae, A madurae, Madurella mycetomatis, M mycetomatis, Streptomyces somaliensis, S somaliensis, Actinomadura pelletieri, A pelletieri
