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Dermatologic Manifestations of Mycetoma

  • Author: Oliverio Welsh, MD(DrSc); Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jul 26, 2013
 

Background

Mycetoma is a chronic, granulomatous disease of the skin and subcutaneous tissue, which sometimes involves muscle, bone, 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 appear 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.

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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 that in some cases can reach more than 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 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.

Salinas-Carmona et al have unveiled aspects of the physiopathogenic mechanisms of experimental actinomycetoma in mice.[6]

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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 incidence 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%).[7] 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.

Age

Mycetoma predominates in individuals aged 20-40 years.

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Contributor Information and Disclosures
Author

Oliverio Welsh, MD(DrSc) Former Chair, Active Emeritus Professor, Department of Dermatology, Universidad Autónoma De Nuevo León, Mexico

Oliverio Welsh, MD(DrSc) is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Lucio Vera-Cabrera, PhD Laboratorio Interdisciplinario de Investigación Dermatológica, Servicio de Dermatología, Hospital Universitario, UANL, Mexico

Lucio Vera-Cabrera, PhD is a member of the following medical societies: American Society for Microbiology

Disclosure: Nothing to disclose.

Mario C Salinas-Carmona, MD, PhD Chair, Department of Immunology, Universidad Autónoma De Nuevo León, Mexico

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Susan M Swetter, MD Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center and Cancer Institute, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, Women's Dermatologic Society, American Society of Clinical Oncology, Society for Melanoma Research, Eastern Cooperative Oncology Group, American Medical Association, Pacific Dermatologic Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

References
  1. Welsh O, Vera-Cabrera L, Salinas-Carmona MC. Mycetoma. Clin Dermatol. 2007 Mar-Apr. 25(2):195-202. [Medline].

  2. Pinoy E. Actinomycoses et mycetomas. Bull Inst Pasteur. 1913. 11:929-38.

  3. 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. 2008 May. 23(5):573-81. [Medline].

  4. 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. 1993 Nov. 31(11):2901-6. [Medline].

  5. Salinas-Carmona MC, Perez-Rivera I. Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis. Infect Immun. 2004 Oct. 72(10):5597-604. [Medline].

  6. Salinas-Carmona MC, Rosas-Taraco AG, Welsh O. Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment. Antonie Van Leeuwenhoek. 2012 Oct. 102(3):473-80. [Medline].

  7. 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. 1992 Jul-Aug. 128(4):477-81. [Medline].

  8. van de Sande WW, Fahal A, Verbrugh H, van Belkum A. Polymorphisms in genes involved in innate immunity predispose toward mycetoma susceptibility. J Immunol. 2007 Sep 1. 179(5):3065-74. [Medline].

  9. Kresch-Tronik NS, Carrillo-Casas EM, Arenas R, Atoche C, Del Río-Ávila C, Ochoa-Carrera LA. First case of mycetoma associated with Nocardia takedensis. J Dermatol. 2013 Feb. 40(2):135-6. [Medline].

  10. Kresch-Tronik NS, Carrillo-Casas EM, Arenas R, Atoche C, Ochoa-Carrera LA, Xicohtencatl-Cortes J. Nocardia harenae, an uncommon causative organism of mycetoma: report on two patients. J Med Microbiol. 2012 Aug. 61(Pt 8):1153-5. [Medline].

  11. Kashima M, Kano R, Mikami Y, et al. A successfully treated case of mycetoma due to Nocardia veterana. Br J Dermatol. 2005 Jun. 152(6):1349-52. [Medline].

  12. 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. 2004 Oct. 42(10):4530-5. [Medline].

  13. 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. 2006 Apr. 19(2):259-82. [Medline].

  14. Desnos-Ollivier M, Bretagne S, Dromer F, Lortholary O, Dannaoui E. Molecular identification of black-grain mycetoma agents. J Clin Microbiol. 2006 Oct. 44(10):3517-23. [Medline].

  15. Vera-Cabrera L, Ortiz-Lopez R, Elizondo-Gonzalez R, Perez-Maya AA, Ocampo-Candiani J. Complete genome sequence of Nocardia brasiliensis HUJEG-1. J Bacteriol. 2012 May. 194(10):2761-2. [Medline]. [Full Text].

  16. Vera-Cabrera L, Campos-Rivera MP, Gonzalez-Martinez NA, Ocampo-Candiani J, Cole ST. In vitro activities of the new antitubercular agents PA-824 and BTZ043 against Nocardia brasiliensis. Antimicrob Agents Chemother. 2012 Jul. 56(7):3984-5. [Medline].

  17. Espinoza-González NA, Welsh O, Ocampo-Candiani J, Said-Fernandez S, Lozano-Garza G, Choi SH. Evaluation of the Combined Therapy of DA-7218, a New Oxazolidinone, and Trimethoprim/ Sulfamethoxazole in the Treatment of Experimental Actinomycetoma by Nocardia brasiliensis. Curr Drug Deliv. 2010 May 24. [Medline].

  18. Vera-Cabrera L, Salinas-Carmona MC, Welsh O, Rodriguez MA. Isolation and purification of two immunodominant antigens from Nocardia brasiliensis. J Clin Microbiol. 1992 May. 30(5):1183-8. [Medline].

  19. Lacroix C, de Kerviler E, Morel P, Derouin F, Feuilhade de Chavin M. Madurella mycetomatis mycetoma treated successfully with oral voriconazole. Br J Dermatol. 2005 May. 152(5):1067-8. [Medline].

  20. 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. 2005 Nov-Dec. 47(6):339-46. [Medline].

  21. N'diaye B, Dieng MT, Perez A, Stockmeyer M, Bakshi R. Clinical efficacy and safety of oral terbinafine in fungal mycetoma. Int J Dermatol. 2006 Feb. 45(2):154-7. [Medline].

  22. 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. 1987 Sep. 17(3):443-8. [Medline].

  23. 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. 2006 May-Jun. 142(3):247-52. [Medline].

  24. Welsh O, Vera-Cabrera L, Welsh E, Salinas MC. Actinomycetoma and advances in its treatment. Clin Dermatol. 2012 Jul. 30(4):372-81. [Medline].

  25. 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. 2008 Sep 10. 2(9):e289. [Medline].

  26. 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. 2009 Jan. 53(1):295-7. [Medline].

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  28. Fahal AH. Management of mycetoma. Exp Rev Dermatol. 2010. 5:87-93.

  29. Hay RJ, Mahgoub ES, Leon G, al-Sogair S, Welsh O. Mycetoma. J Med Vet Mycol. 1992. 30 Suppl 1:41-9. [Medline].

  30. Mahgoub ES, Murray IG. Mycetoma. London, England: William Heinemann; 1973. 76-115.

  31. 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. 2006 Aug 1. 177(3):1997-2005. [Medline].

  32. 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. 2006 Sep. 50(9):3170-2. [Medline].

 
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Actinomycetoma of the foot (left) and arm (center) caused by Nocardia brasiliensis. Multiple nodules and fistulae are present. Microscopic examination of the pus (right). Granules are observed, which are multilobulated and 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, Scedosporium apiospermum (Pseudallescheria boydii) (right).
Table 1. Fungi Causing Mycetoma
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
Table 2. Microorganisms Causing Actinomycetomas in Humans
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[11] --
Nocardia mexicana[12] --
N harenae --
N takedensis --
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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