Dermatologic Manifestations of Mycetoma
- Author: Oliverio Welsh, MD DrSc; Chief Editor: Dirk M Elston, MD more...
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 1913, 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.[2]
Also see the 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 lesions 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) – 1-beta, 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).[3]
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 useful for diagnosis.[4] Immunoglobulin M anti– N brasiliensis antibodies can protect mice from an experimental infection.[5] Activation of cellular immunity and production of cytokines are involved in resistance and elimination of the N brasiliensis bacterial cells.
Epidemiology
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. Sudan, Mexico, Venezuela, 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, among eumycetomas, Madurella mycetomatis, and in actinomycetomas, Streptomyces somaliensis and Actinomadura pelletieri. In Mexico, which shares common climatic conditions with the African countries, most cases are found in rural areas and 98% are caused by actinomycetes, mainly N brasiliensis (86%) and Actinomadura madurae (about 8%).[6] In India, 65% of cases are produced by actinomycetes and the rest by eumycetes, mostly M mycetomatis.
Worldwide, approximately 60% of mycetomas cases are of actinomycotic origin.
Mortality/Morbidity
Mycetoma is usually painless; individuals who are affected seek medical attention mainly because of tumefaction and draining sinuses. In cases affecting the thorax or the head, mycetoma can be potentially fatal because of the spread of microorganisms to adjacent organs. Rarely, the disease spreads 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.
Welsh O, Vera-Cabrera L, Salinas-Carmona MC. Mycetoma. Clin Dermatol. Mar-Apr 2007;25(2):195-202. [Medline].
Pinoy E. Actinomycoses et mycetomas. Bull Inst Pasteur. 1913;11:929-38.
Solis-Soto JM, Quintanilla-Rodriguez LE, Meester I, et al. In situ detection and distribution of inflammatory cytokines during the course of infection with Nocardia brasiliensis. Histol Histopathol. May 2008;23(5):573-81. [Medline].
Salinas-Carmona MC, Welsh O, Casillas SM. Enzyme-linked immunosorbent assay for serological diagnosis of Nocardia brasiliensis and clinical correlation with mycetoma infections. J Clin Microbiol. Nov 1993;31(11):2901-6. [Medline].
Salinas-Carmona MC, Perez-Rivera I. Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis. Infect Immun. Oct 2004;72(10):5597-604. [Medline].
Lopez Martinez R, Mendez Tovar LJ, Lavalle P, Welsh O, Saul A, Macotela Ruiz E. [Epidemiology of mycetoma in Mexico: study of 2105 cases]. Gac Med Mex. Jul-Aug 1992;128(4):477-81. [Medline].
van de Sande WW, Fahal A, Verbrugh H, van Belkum A. Polymorphisms in genes involved in innate immunity predispose toward mycetoma susceptibility. J Immunol. Sep 1 2007;179(5):3065-74. [Medline].
Kashima M, Kano R, Mikami Y, et al. A successfully treated case of mycetoma due to Nocardia veterana. Br J Dermatol. Jun 2005;152(6):1349-52. [Medline].
Rodriguez-Nava V, Couble A, Molinard C, Sandoval H, Boiron P, Laurent F. Nocardia mexicana sp. nov., a new pathogen isolated from human mycetomas. J Clin Microbiol. Oct 2004;42(10):4530-5. [Medline].
Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. Apr 2006;19(2):259-82. [Medline].
Desnos-Ollivier M, Bretagne S, Dromer F, Lortholary O, Dannaoui E. Molecular identification of black-grain mycetoma agents. J Clin Microbiol. Oct 2006;44(10):3517-23. [Medline].
Vera-Cabrera L, Salinas-Carmona MC, Welsh O, Rodriguez MA. Isolation and purification of two immunodominant antigens from Nocardia brasiliensis. J Clin Microbiol. May 1992;30(5):1183-8. [Medline].
Lacroix C, de Kerviler E, Morel P, Derouin F, Feuilhade de Chavin M. Madurella mycetomatis mycetoma treated successfully with oral voriconazole. Br J Dermatol. May 2005;152(5):1067-8. [Medline].
Negroni R, Tobon A, Bustamante B, Shikanai-Yasuda MA, Patino H, Restrepo A. Posaconazole treatment of refractory eumycetoma and chromoblastomycosis. Rev Inst Med Trop Sao Paulo. Nov-Dec 2005;47(6):339-46. [Medline].
N'diaye B, Dieng MT, Perez A, Stockmeyer M, Bakshi R. Clinical efficacy and safety of oral terbinafine in fungal mycetoma. Int J Dermatol. Feb 2006;45(2):154-7. [Medline].
Welsh O, Sauceda E, Gonzalez J, Ocampo J. Amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of actinomycotic mycetoma. J Am Acad Dermatol. Sep 1987;17(3):443-8. [Medline].
Fuentes A, Arenas R, Reyes M, Fernandez RF, Zacarias R. [Actinomycetoma and Nocardia sp. Report of five cases treated with imipenem or imipenem plus amikacin]. Gac Med Mex. May-Jun 2006;142(3):247-52. [Medline].
Welsh O, Vera L, Welsh E, Salinas MC. Actinomycetoma and advances in its treatment. Clin Dermatol. 2011;In press.
Vera-Cabrera L, Daw-Garza A, Said-Fernandez S, et al. Therapeutic Effect of a Novel Oxazolidinone, DA-7867, in BALB/c Mice Infected with Nocardia brasiliensis. PLoS Negl Trop Dis. Sep 10 2008;2(9):e289. [Medline].
Chacon-Moreno BE, Welsh O, Cavazos-Rocha N, et al. Efficacy of ciprofloxacin and moxifloxacin against Nocardia brasiliensis in vitro and in an experimental model of actinomycetoma in BALB/c mice. Antimicrob Agents Chemother. Jan 2009;53(1):295-7. [Medline].
Welsh O. Mycetoma. Current concepts in treatment. Int J Dermatol. Jun 1991;30(6):387-98. [Medline].
Fahal AH. Management of mycetoma. Exp Rev Dermatol. 2010;5:87-93.
Hay RJ, Mahgoub ES, Leon G, al-Sogair S, Welsh O. Mycetoma. J Med Vet Mycol. 1992;30 Suppl 1:41-9. [Medline].
Mahgoub ES, Murray IG. Mycetoma. London, England: William Heinemann; 1973:76-115.
Mariat F, Destombes P, Segretain G. The mycetomas: clinical features, pathology, etiology and epidemiology. Contrib Microbiol Immunol. 1977;4:1-39. [Medline].
van de Sande WW, Janse DJ, Hira V, et al. Translationally controlled tumor protein from Madurella mycetomatis, a marker for tumorous mycetoma progression. J Immunol. Aug 1 2006;177(3):1997-2005. [Medline].
Vera-Cabrera L, Gonzalez E, Rendon A, et al. In vitro activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensis. Antimicrob Agents Chemother. Sep 2006;50(9):3170-2. [Medline].
| White grain | Black grain |
| Acremonium falciforme | Exophiala jeanselmei |
| Acremonium kiliense | Madurella grisea |
| Acremonium recifei | M mycetomatis |
| Cylindrocarpon destructans | M pseudomycetomatis |
| Fusarium moniliforme | Leptosphaeria tomkinsii |
| Fusarium solani | Leptosphaeria senegalensis |
| Neotestudina rosatii | Pyrenochaeta mackinnonii |
| Pseudallescheria boydii | Pyrenochaeta romeroi |
| ---------------- | Phlenodomus avramii |
| 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[8] | -- |
| Nocardia mexicana[9] | -- |
| 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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