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Mycetoma is a chronic progressive granulomatous infection of the skin and subcutaneous tissue most often affecting the lower extremities, typically a single foot. The disease is unique from other cutaneous or subcutaneous diseases in its triad of localized swelling, underlying sinus tracts, and production of grains or granules (composed of aggregations of the causative organism) within the sinus tracts. These infections may be caused by fungi and termed eumycotic mycetoma or eumycetoma, or by filamentous higher bacteria and termed actinomycotic mycetoma or actinomycetoma. The term mycetoma can also be found in the literature incorrectly referring to a fungus ball found in a preexisting cavity in the lung or within a paranasal sinus, most often caused by Aspergillus spp. Grain formation by infecting organisms is restricted to the diseases mycetoma, actinomycosis (see Chapter 254 ), and botryomycosis. Actinomycosis is a disease produced by the anaerobic and microaerophilic higher bacteria that normally colonize the mouth and gastrointestinal and urogenital tracts. The portal of entry in actinomycosis is from those colonized sites, whereas in mycetoma the portal is the skin and subcutaneous tissue into which the organism was inoculated by minor trauma. Botryomycosis is a chronic bacterial infection of soft tissues in which the causative organism, often Staphylococcus aureus, is found in loose clusters among the pus. In a rare form of ringworm called dermatophyte mycetoma, there are also loosely compacted clusters of hyphae in subcutaneous pus. In contrast, mycetoma grains are dense clusters of organisms.
Etiologic Agents
The agents of mycetoma are fungi and aerobic filamentous bacteria that have been found on plants and in the soil. The predominance of bacterial versus fungal causes of mycetoma varies among geographic locations. Eumycotic (true fungal) disease is caused by a variety of fungal organisms. These can be divided into those that form dark grains and those that form pale or white grains ( Table 261.1 ). Color distinctions are made by observing unstained specimens. Among the fungi causing dark-grained mycetoma, the most common are Madurella mycetomatis, Falciformispora (formerly Leptosphaeria ) senegalensis, and Trematosphaeria grisea. Other agents include Corynespora cassicola, Curvularia geniculata, Curvularia lunata, Emarellia grisea, Emarellia paragrisea, Exophiala jeanselmei, Exophiala oligosperma, Falciformispora (formerly Leptosphaeria ) tompkinsii, Madurella fahalii, Madurella pseudomycetomatis, Madurella tropicana, Phialophora verrucosa, Plenodomas avramii, Pseudochaetosphaeronema larense, Rhinocladiella atrovirens, Medicopsis (formerly Pyrenochaeta ) mackinnonii, Biatriospora spp., Roussoella spp., Rhytidhysteron spp., and Medicopsis (formerly Pyrenochaeta ) romeroi. Scedosporium apiospermum complex species are the most common cause of pale-colored grains. Other fungi in that category include Fusarium (formerly Acremonium ) falciforme, Sarocladium (formerly Acremonium ) kiliense, Acremonium recifei, Aspergillus flavus, Aspergillus hollandicus, Aspergillus nidulans, Phialophora (formerly Cylindrocarpon ) cyanescens, Cylindrocarpon destructans, Diaporthe phaseolorum, Fusarium solani, Fusarium moniliforme, Fusarium keratoplasticum, Fusarium pseudensiforme, Neotestudina rosatii, Phaeoacremonium spp., Pleurostomophora ochracea, and Polycytella hominis.
TABLE 261.1
Typical Morphologic Features of Mycetoma Grains
| GRAIN COLOR | CAUSATIVE AGENT |
|---|---|
| Eumycetoma (Eumycotic Mycetoma) a | |
| Black grains | Madurella spp., Biatriospora spp., Trematosphaeria spp., Pseudochaetosphaeroma spp., Roussoella spp., Rhytidhysteron spp., Curvularia spp., Exophiala spp., Falciformispora spp., Medicopsis spp., Phaeoacremonium spp., Phialophora verrucosa |
| Pale grains (white to yellow) | Scedosporium apiospermum complex, Aspergillus spp., Diaporthe phaseolorum, Fusarium spp., Neotestudina rosatii, Pleurostomophora ochracea |
| Actinomycetoma (Actinomycotic Mycetoma) b | |
| Pale grains (white to yellow) | Actinomadura madurae, Nocardia spp. |
| Yellow to brown grains | Streptomyces somaliensis |
| Red to pink grains | Actinomadura pelletieri |
a Hyphae of 2- to 5-µm diameter are observed within grain.
b Filaments of 0.5- to 1-µm diameter are observed within grain.
Actinomycetoma is caused by members of the order Actinomycetales, most commonly Nocardia brasiliensis, Actinomadura madurae, Streptomyces somaliensis, and Actinomadura pelletieri. Cases have been reported that were caused by Actinomadura latina, Nocardia aobensis, Nocardia farcinica, Nocardia harenae, Nocardia otitidiscaviarum (formerly N. caviae ), Nocardia mexicana, Nocardia transvalensis, Nocardia veterana, Nocardia yamanashiensis, and Nocardiopsis dassonvillei. Actinomycetoma grains are typically white or pale yellow, except those caused by Actinomadura pelletieri, which are red to pink.
Some reports use species names that are not currently recognized, leaving in doubt the identification. The modern use of molecular techniques, including polymerase chain reaction, DNA sequencing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), has both assisted in better identifying and classifying the agents of mycetoma, and made comparisons between current and previous pathogen identification difficult to track.
Epidemiology
The oldest description of this disease appears to date back to the ancient Indian Sanskrit text Atharva Veda, in which reference is made to pada valmikam, translated to mean “anthill foot.” More modern descriptions from Madras, India, in the 19th century led to this disease initially being called “madura foot,” or maduromycosis, a term still used by some today to describe eumycotic mycetoma. Mycetoma is most commonly found in tropical and subtropical climates, with the highest incidence reported from endemic areas in the Indian subcontinent, the Middle East, Africa, and Central and South America. One of the largest current groups of cases is in Sudan. Only scattered reports describe cases originating in the United States, Europe, and Japan. Disease occurs around five times more frequently in males, commonly in the 20- to 40-year-old age range. Disease is more common in agricultural workers and outdoor laborers but is not exclusively seen in rural areas. Disease occurs sporadically throughout most areas of the world, and some postulate that the increased numbers in tropical regions may also result in part from less use of protective clothing, chiefly shoes, in the warmer, poorer endemic regions.
The causative agents of mycetoma vary from region to region and with climate. Worldwide, M. mycetomatis is the most common cause of this disease, but A. madurae, M. mycetomatis, and S. somaliensis are more commonly reported from drier regions, whereas S. apiospermum complex spp., Nocardia spp., and A. pelletieri are more common in those areas with higher annual rainfall. In India, Nocardia spp. and T. grisea are the most common causes of mycetoma; in the Middle East, M. mycetomatis and S. somaliensis; in West Africa, F. senegalensis; and in East Africa, M. mycetomatis and S. somaliensis. In Central and South America, T. grisea and Nocardia spp. are the common causes of mycetoma, and in the United States, S. apiospermum complex spp. are the most commonly recovered causative agent.
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