eMedicine Specialties > Dermatology > Fungal Infections

Mycetoma: Differential Diagnoses & Workup

Author: Oliverio Welsh, MD, DSc, Former Chair, Active Emeritus Professor, Department of Dermatology, Universidad Autónoma De Nuevo León, Mexico
Coauthor(s): Lucio Vera-Cabrera, PhD, Professor, Department of Internal Medicine, Dr. Jose Eleuterio Gonzalez University Hospital, Autonomous University of Nuevo Leon, México; Mario C Salinas-Carmona, MD, PhD, Chair, Department of Immunology, Universidad Autónoma De Nuevo León, Mexico
Contributor Information and Disclosures

Updated: Mar 26, 2009

Differential Diagnoses

Coccidioidomycosis
Cutaneous Tuberculosis
Sporotrichosis

Other Problems to Be Considered

Botryomycosis
Other deep fungal infections
Osteomyelitis
Bone and soft tissue tumors

Workup

Laboratory Studies

  • The first important goal is to differentiate between eumycetoma and actinomycotic mycetoma because treatment is completely different. The most useful procedures for establishing the diagnosis of mycetoma are direct examination with potassium hydroxide (KOH), biopsy, and microbiological cultures.
    • Differentiation is accomplished by microscopic examination of exudate from the draining sinuses. Actinomycetes occur with granules of about 100 µm in diameter, with delicate, branched filaments measuring about 1 µm in diameter. Fungal grains are observed as a mass of hyphae embedded in intercellular cement, and the filaments are wider than 1 µm.
    • Observing the size of the filaments and the color of the granules is important because these characteristics are helpful for initial presumptive identification of the etiologic agent.
  • Culture of the lesion is performed by collection of the abscess or the fistula secretion or by tissue biopsy. In both cases, the samples are cultured in media such as Sabouraud agar or mycobiotic agar to isolate fungi and/or blood agar to isolate bacteria. The etiologic agents are identified according to their macroscopic and microscopic features.
  • Biochemical tests are particularly useful to identify actinomycetes, although a more conclusive identification is performed by sequencing analysis of the small ribosomal subunit gene or sequencing of conserved genes such as HSP65.8,9
  • An enzyme-linked immunosorbent assay (ELISA) to determine anti– N brasiliensis antibodies is used for diagnosis and to assess response to medical treatment.10

Imaging Studies

  • Radiologic tests (bone radiographs) should be performed if underlying bony involvement is suspected.

Other Tests

  • Immunologic tests
    • Several immunologic assays using culture filtrate or cytoplasmic antigens of mycetoma agents have been developed to detect antibodies. In the case of N brasiliensis, it has been observed by Western blot that the humoral response is directed against 3 proteins of 24, 26, and 61 kd of a cellular extract. These proteins were isolated and purified, and the 24- and 26-kd proteins were used to develop an ELISA to detect antibodies against N brasiliensis.11 A correlation between antibody titers and clinical condition of the patients was observed. In patients with active disease, the titers were high. In patients with cured lesions, the optical density in the ELISA test was below the cut-off point, with similar results to those obtained with negative controls. To date, the use of a skin antigen for diagnosis has been of little help because of the cross-reactivity with other bacterial infections, such as tuberculosis or leprosy.
    • Regarding the eumycotic mycetoma infections, immunodiffusion tests have been used to detect antibodies. In the case of mycetoma caused by M mycetomatis, an immunodominant protein has been described to induce specific antibodies, which are useful for the identification and prognosis of M mycetomatis mycetoma. A good animal model for studying eumycotic mycetoma has not yet been developed.

Histologic Findings

The histopathologic picture reveals a granulomatous inflammation with abscess formation. A central zone exists where polymorphonuclear cells are abundant and granules or grains are found. This central zone is surrounded by lymphocytes, plasma cells, histiocytes, and fibroblasts. The actinomycetes are seen by staining with hematoxylin and eosin (H&E), Gram, Gridley, and Grocott stains; the eumycetes are more easily observed with H&E, periodic acid-Schiff (PAS), and Grocott/methenamine-silver stains.

More on Mycetoma

Overview: Mycetoma
Differential Diagnoses & Workup: Mycetoma
Treatment & Medication: Mycetoma
Follow-up: Mycetoma
Multimedia: Mycetoma
References
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References

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

  2. 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].

  3. 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].

  4. 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].

  5. 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].

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

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

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

  21. Mariat F, Destombes P, Segretain G. The mycetomas: clinical features, pathology, etiology and epidemiology. Contrib Microbiol Immunol. 1977;4:1-39. [Medline].

  22. 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].

  23. 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].

  24. Welsh O. Mycetoma. Current concepts in treatment. Int J Dermatol. Jun 1991;30(6):387-98. [Medline].

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Further Reading

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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

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Contributor Information and Disclosures

Author

Oliverio Welsh, MD, DSc, Former Chair, Active Emeritus Professor, Department of Dermatology, Universidad Autónoma De Nuevo León, Mexico
Oliverio Welsh, MD, DSc is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Lucio Vera-Cabrera, PhD, Professor, Department of Internal Medicine, Dr. Jose Eleuterio Gonzalez University Hospital, Autonomous University of Nuevo Leon, México
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.

Medical Editor

Susan M Swetter, MD, Director, Pigmented Lesion and Cutaneous Melanoma Clinic, Associate Professor, Department of Dermatology, Stanford University Medical Center, Veterans Affairs Palo Alto Health Care System
Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, Pacific Dermatologic Association, Society for Investigative Dermatology, Society for Melanoma Research, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

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, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

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