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Dermatologic Manifestations of Mycetoma Clinical Presentation

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

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.

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Physical

Examination typically reveals a painless firm 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 arms and legs, particularly the feet and 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, the head, and the neck. See the images below.

Actinomycetoma of the foot (left) and arm (center) 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). Microscop 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).
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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 characteristics of the causative agents, it has recently 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.[8]

New agents have recently been identified as causing actinomycetoma (Nocardia harenae and Nocardia takedensis). The clinical pictures are similar, and identification has been achieved by genomic technique.[9, 10]

Table 1. Fungi Causing Mycetoma (Open Table in a new window)

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 (Open Table in a new window)

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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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
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  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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