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Dermatology > FUNGAL INFECTIONS
Eumycetoma (Fungal Mycetoma)
Article Last Updated: Oct 2, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: George W Turiansky, MD, Associate Professor, Department of Dermatology, Uniformed Services University of the Health Sciences; Director, National Capital Consortium Dermatology Residency Program, Walter Reed Army Medical Center
George Turiansky is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, Association of Professors of Dermatology, and Ukrainian Medical Association of North America
Editors: Daniel J Hogan, MD, Director of Bay Pines Dermatology Residency Program, Bay Pines Veterans Affairs Healthcare System; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
Madura foot, maduromycosis, fungal mycetoma, eumycotic mycetoma, melanoid mycetoma, ochroid mycetoma
Background
Eumycetoma is a chronic cutaneous and subcutaneous infection caused by various genera of fungi. Approximately 40% of mycetomas worldwide are eumycotic as opposed to actinomycotic (ie, caused by bacterial actinomycetes). The disease is marked by progressive destruction of soft tissue and nearby anatomic structures.
Gill, who worked at a dispensary in the southern Indian province of Madura, first recognized mycetomas as a disease entity in 1842. Godfrey first documented a case of mycetoma in Madras, India. Native peoples of the province of Madura commonly called the disease Madura foot. In 1860, Carter, who established the fungal etiology of this disorder, first proposed the term mycetoma. In 1872, Carter further proposed the terms melanoid and ochroid in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) produced by the etiologic agents.
Pathophysiology
The foot is the most common site of infection, and 70% of all mycetomas affect the foot. Other reported sites of involvement include the upper extremities, trunk, buttocks, eyelids, lacrimal glands, paranasal sinuses, mandible, scalp, neck, perineum, and testes. The disease is initially limited to the skin and subcutaneous tissue but may eventually spread through the fascial planes to contiguous structures such as muscle, bone, blood and lymphatic vessels, and nerves. Rarely, the disease may spread to the regional lymph nodes or viscera.
Frequency
United States
Sporadic cases have been reported in North America. In the United States, epidemiologic data from 1896-1964 include only 30 cases of eumycetoma, with the highest incidence in the Southwest. Mycetoma is common in Mexico; in the United States, physicians in Texas and other border states are most likely to encounter patients with mycetoma.
International
Eumycetoma is mainly a disease of the tropical and subtropical zones especially between the Tropic of Cancer and the Tropic of Capricorn, that is, between the latitudes 15° S and 30° N. Eumycetoma is endemic in India, parts of Africa (eg, Sudan, Senegal, Somalia, Nigeria, Zaire, Chad), Pakistan, Yemen, Mexico, Central America, South America (eg, Guatemala, Venezuela, Colombia, Brazil), and Indonesia.
Mortality/Morbidity
Eumycetoma can be associated with significant morbidity in terms of gradual enlargement and deformity of the infected site. Severe involvement of the lower extremity may impair ambulation.
Sex
The disease incidence is higher in males than females, with a ratio of 4-5:1.
Age
The disease incidence is highest in persons aged 10-40 years.
History
- Many cases are painless, although painful lesions may prompt the individual to seek medical attention.
- Gradual enlargement of the affected site and difficulties with ambulation may also prompt affected persons to seek care.
- Predisposing factors include the following:
- History of trauma
- Walking barefoot
- Agricultural work
- Poor personal hygiene
- Poor nutrition
- Wounds or multiple infections
Physical
- The foot is the most common site of infection; 70% of all mycetomas affect the foot.
- Other reported sites of involvement include the following:
- Upper extremities
- Trunk
- Buttocks
- Eyelids
- Lacrimal glands
- Paranasal sinuses
- Mandible
- Scalp
- Neck
- Perineum
- Testes
- The disease is initially limited to the skin and subcutaneous tissue but may eventually spread through the fascial planes to contiguous structures, as follows:
- Muscle
- Bone
- Blood and lymphatic vessels
- Nerves
- Rarely, the disease may spread to the regional lymph nodes or viscera.
- Eumycetoma is characterized by the clinical triad of tumefaction, draining sinuses, and granules (see Images 1-2).
- The disease usually begins as a painless swelling or thickening of the skin and subcutaneous tissue.
- As the disease gradually progresses over months or years, the initial lesion enlarges and eventually becomes tumorous.
- The overlying skin may be smooth, dyspigmented, or shiny.
- Abscesses and sinus tracts develop over time and may contain a serosanguineous or seropurulent discharge, which may contain white-to-yellow or black granules.
- Granules are firm 0.2- to 5-mm aggregates of organized vegetative, septate hyphae, which often are embedded in a matrix cement substance.
- These granules are usually macroscopic and are observed in the lesional tissue and in sinus tracts.
- The color of the dark grains is thought to be due to melanin, host protein, and dark debris.
- Regional lymphadenitis secondary to bacterial superinfection of the lesion may be present.
Causes
Agents that cause eumycetoma are primarily saprophytic microorganisms that are found in the soil and on plant matter. Healthy persons become inoculated with these agents as a result of the traumatic implantation of thorns, splinters, and other plant matter. Pseudallescheria boydii is the most common etiologic agent of eumycetoma in the United States. Madurella mycetomatis accounts for most cases worldwide. Madurella grisea is a common etiologic agent in South America. Leptosphaeria senegalensis and Leptosphaeria tompkinsii are common causes of eumycetoma in West Africa. In general, the geographic distribution of the various mycetoma agents is related to the amount of rainfall and other climatic conditions. Each geographic region has a different list of most common agents. Fungi that cause eumycetoma include the following:
- Those with a white-to-yellow granule
- Acremonium species
- Aspergillus nidulans
- Aspergillus flavus
- Cylindrocarpon cyanescens
- Cylindrocarpon destructans
- Fusarium species
- Neotestudina rosatii
- Polycytella hominis
- P boydii
- Those with a black granule
- Corynespora cassicola
- Curvularia species
- Exophiala jeanselmei
- L senegalensis
- L tompkinsii
- M grisea
- M mycetomatis
- Phialophora verrucosa
- Plenodomus auramii
- Pyrenochaeta mackinnonii
- Pyrenochaeta romeroi
Cutaneous Tuberculosis
Sporotrichosis
Squamous Cell Carcinoma
Syphilis
Verrucous Carcinoma
Yaws
Other Problems to be Considered
Actinomycetoma
Botryomycosis
Chromoblastomycosis
Sporotrichosis
Tuberculosis
Blastomycosis
Coccidioidomycosis
Elephantiasis
Osteomyelitis
Malignancy
Yaws (eg, frambesia tropica)
Lab Studies
- Identification of the etiologic agent of eumycetoma is based on direct microscopic examination of the granules, culture isolation of the agent, colonial features and fungal microscopic morphology.
- Eumycetoma granules can be crushed and examined at microscopy with direct wet mounts after treatment with 10-20% potassium hydroxide, lactophenol cotton blue, Albert stain, or physiologic saline solution.
- Eumycetoma agents appear as broad, septate, branching hyphae 2-5 µm in diameter or, as in the case of E jeanselmei, as a compact mass of rounded cells.
- Fresh granules can be teased from lesional tissue or biopsy specimens. These cells can be washed in saline solution or saline solution containing antibiotics prior to culturing on fungal media such as Sabouraud dextrose agar, blood agar, or a brain-heart infusion containing antibiotics.
- Granules from draining sinus tracts may not be optimal for culturing because of bacterial contamination.
- Recently, Ahmed et al reported 2 cases of leg eumycetoma due to M mycetomatis that were successfully identified by species-specific polymerase chain reaction and DNA sequencing.
Imaging Studies
- Radiographs, CT scans, and MRIs demonstrate the presence and extent of bone or organ involvement.
- Changes of underlying bony structures may include the following:
- Osteoporosis
- Bony destruction
- Loss of cortical margin with bony erosion
- Punched-out lytic lesions
- Osteophyte formation
- Osteomyelitis
- Periosteal elevation
- Marrow infiltration
- Coarse trabecular pattern
- Bony expansion
Histologic Findings
A biopsy specimen should be obtained from a small abscess or from the sinus tract. Hematoxylin-eosin stained sections reveal extensive granulation tissue containing abscesses. Granules of 0.2-5.0 mm in diameter may be found in abscesses or sinuses. Eumycotic granules have positive results with periodic acid–Schiff and Gomori methenamine silver stains. They contain gram-negative septate hyphae that are 2-5 µm in diameter. Eosinophilic material may be seen deposited around the granule; this material represents an immunologic response, the Splendore-Hoeppli reaction.
Medical Care
- Treatment of eumycetoma remains problematic.
- Historically, the treatment of eumycetoma has included surgical treatment, medical treatment, or both.
- Combined surgical and medical treatment appears to be the management option of choice.
- Antifungal therapy has variable results.
- The sensitivity of organisms to antifungal drugs in vitro is not necessarily correlated with the in vivo response.
- Amphotericin B has minimal or no effect on eumycetoma organisms.
- Anecdotal reports of successful treatment with griseofulvin and dapsone exist.
- In one study, a case of eumycetoma due to M grisea initially responded to fluconazole 400 mg/d but worsened after the patient stopped the treatment.
- In the same report, 2 other cases due to M mycetomatis and P boydii had either slight improvement or only transient clinical improvement with fluconazole 200-400 mg/d for 3 months. These cases were classified as nonresponsive.
- Azole antifungal agents such as ketoconazole have some effectiveness.
- Mahgoub and Gumaa demonstrated that ketoconazole is effective in the treatment of eumycetoma caused by M mycetomatis.
- They treated 13 patients with oral ketoconazole 200-400 mg/d; 5 patients were cured, and 4 patients improved.
- The median treatment duration was 12.9 months, with a treatment range of 3-36 months.
- Cures were noted with the higher dosages of ketoconazole.
- Itraconazole is variably effective in the treatment of eumycetoma due to various organisms. Recently, a case of eumycetoma due to M mycetomatis without bony involvement was successfully treated with oral voriconazole at 600 mg/d, with a 4-year disease free follow-up.
- A recent study by N'Diaye et al showed that high-dose terbinafine (500 mg bid) for 24-48 weeks was generally well tolerated. In the investigators' overall opinion at the end of the study, of 20 eumycetoma patients who completed the study, 5 patients were clinically cured and 11 were clinically improved.
Surgical Care
- Treatment in the past has included amputation of the affected limb or other radical surgery.
- Although surgical treatment alone results in recurrence rates as high as 80%, surgical resection with a wide surgical margin of uninfected tissue may be useful in early, small lesions without bony involvement.
- Surgical debulking together with oral antifungal treatment may be necessary with chronic extensive lesions.
The use of various antifungal agents in the treatment of eumycetoma has been reported. Imidazole antifungal agents appear to be the agents of choice. Of the azole group of antifungal agents, ketoconazole appears to be antifungal agent of choice, although isolated reports of successful treatment with itraconazole exist.
Drug Category: Antifungal agents
Reportedly, imidazole antifungal agents are variably effective in the treatment of eumycetoma when they are used alone or in conjunction with surgical therapy.
| Drug Name | Ketoconazole (Nizoral) |
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| Description | Synthetic imidazole antifungal agent. Broad-spectrum agent known to be a potent inhibitor of cytochrome P-450 3A4 enzyme system in vitro. Inhibition of this system impairs synthesis of ergosterol, a vital component of fungal cell membranes. |
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| Adult Dose | 200-600 mg PO qd |
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| Pediatric Dose | <2 years: Not established
>2 years: 3.3-6.6 mg/kg PO qd |
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| Contraindications | Documented hypersensitivity; fungal meningitis; concurrent use with astemizole, terfenadine, cisapride, or oral triazolam |
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| Interactions | Isoniazid may decrease bioavailability; rifampin coadministration decreases effects of either drug; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dose can be adjusted); may decrease theophylline levels; coadministration with cisapride can cause adverse cardiovascular effects (possibly death); coadministration of triazolam or midazolam is contraindicated due to possible increased sedative and hypnotic effects; coadministration of oral HMG-CoA reductase inhibitors lovastatin and simvastatin is contraindicated due to potential risk of rhabdomyolysis and myopathy |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Hepatic toxicity, including rare fatalities, reported; monitor hepatic function at baseline and during treatment; carefully monitor patients requiring prolonged treatment, those taking concurrent potentially hepatotoxic drugs, and those with preexisting liver disease; may elevate plasma concentrations of concomitant drugs; various classes of drugs can decrease antifungal plasma drug concentrations (thoroughly review package inserts prior to concomitant use of these antifungal agents); anaphylaxis rare; mild GI intolerance; imidazoles can interfere with production of endogenous steroids, resulting in irregular bleeding in women and gynecomastia in men; administer antacids, anticholinergics, or H2-blockers at least 2 h after dose |
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| Drug Name | Itraconazole (Sporanox) |
|---|
| Description | Triazole antifungal agent known to be a potent inhibitor of the cytochrome P-450–dependent synthesis of ergosterol in vitro. Slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes. |
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| Adult Dose | 100-300 mg PO qd |
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| Pediatric Dose | Solution
<6 months: Not established
6 months-12 year: 5 mg/kg/d PO for 2 wk
Cap
<3 years: Not established
3-16 years: 100 mg/d PO
>16 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; coadministration with cisapride, dofetilide, oral midazolam, pimozide, levacetylmethadol (levomethadyl), quinidine, lovastatin, simvastatin, triazolam, ergot alkaloids metabolized by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine), methylergometrine (methylergonovine); congestive heart failure or history of congestive heart failure; pregnant women or women contemplating pregnancy |
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| Interactions | Antacids may reduce absorption; edema may occur with coadministration of calcium-channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; high doses may increase tacrolimus and cyclosporine plasma concentrations; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin); cisapride coadministration can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered) |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Caution in hepatic insufficiency |
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Further Outpatient Care
- A prolonged follow-up period is necessary to monitor for disease recurrence.
Special Concerns
- Opinions or assertions contained herein are the private views of the author and are not to be considered as official or as reflecting the views of the US Army, the Department of Defense, or the United States Government.
| Media file 1:
Eumycetoma of the leg with tumefaction, deformity, and multiple sinus tracts in a patient from Costa Rica. Courtesy of Mervyn L. Elgart, MD, Washington, DC. |
 |  View Full Size Image | |
Media type: Photo
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| Media file 2:
Eumycetoma of the foot with tumefaction, deformity, and multiple sinus tracts. Courtesy of Mervyn L. Elgart, MD, Washington, DC. |
 | View Full Size Image | |
Media type: Photo
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- Abbott P. Mycetoma in the Sudan. Trans R Soc Trop Med Hyg. Jan 1956;50(1):11-24; discussion, 24-30. [Medline].
- Ahmed AO, Desplaces N, Leonard P, et al. Molecular detection and identification of agents of eumycetoma: detailed report of two cases. J Clin Microbiol. Dec 2003;41(12):5813-6. [Medline].
- Carter HV. On a new and striking form of fungus disease principally affecting the foot and prevailing endemically in many parts of India. Transactions of the Medical and Physical Society of Bombay. 1860;6:104-42.
- Carter HV. On mycetoma or the fungus disease of India. London, England: J & A Churchill;. 1874.
- Degavre B, Joujoux JM, Dandurand M, Guillot B. First report of mycetoma caused by Arthrographis kalrae: successful treatment with itraconazole. J Am Acad Dermatol. Aug 1997;37(2 Pt 2):318-20. [Medline].
- Diaz M, Negroni R, Montero-Gei F, et al. A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan-American Study Group. Clin Infect Dis. Mar 1992;14(suppl 1):S68-S76. [Medline].
- Green WO, Adams TE. Mycetoma in the United States; a review and report of seven additional cases. Am J Clin Pathol. Jul 1964;42:75-91. [Medline].
- Hay RJ, Mackenzie DW. Mycetoma (madura foot) in the United Kingdom--a survey of forty-four cases. Clin Exp Dermatol. Sep 1983;8(5):553-62. [Medline].
- Hay RJ, Mahgoub ES, Leon G, et al. Mycetoma. J Med Vet Mycol. 1992;30(suppl 1):41-9. [Medline].
- Lacroix C, de Kerviler E, Morel P, et al. Madurella mycetomatis mycetoma treated successfully with oral voriconazole. Br J Dermatol. May 2005;152(5):1067-8. [Medline].
- Lee MW, Kim JC, Choi JS, et al. Mycetoma caused by Acremonium falciforme: successful treatment with itraconazole. J Am Acad Dermatol. May 1995;32(5 pt 2):897-900. [Medline].
- Mahgoub ES, Murray IG. Mycetoma. London: William Heinemann Medical Books. 1973;1-5, 47-53.
- Mahgoub ES. Mycetoma. Semin Dermatol. 1985;4:230-9.
- Mahgoub ES, Gumaa SA. Ketoconazole in the treatment of eumycetoma due to Madurella mycetomii. Trans R Soc Trop Med Hyg. 1984;78(3):376-9. [Medline].
- Mariat F, Destombes P, Segretain G. The mycetomas: clinical features, pathology, etiology and epidemiology. Contrib Microbiol Immunol. 1977;4:1-39. [Medline].
- McGinnis MR. Mycetoma. Dermatol Clin. Jan 1996;14(1):97-104. [Medline].
- Murray PR, ed. Manual of Clinical Microbiology. 7th ed. Washington, DC:. Amercian Society for Microbiology;1999:1318-26.
- N'Diaye B, Dieng MT, Perez A, et al. Clinical efficacy and safety of oral terbinafine in fungal mycetoma. Int J Dermatol. Feb 2006;45(2):154-7. [Medline].
- Rippon JW. Medical mycology: the pathogenic fungi and the pathogenic actinomycetes. Philadelphia, Pa:. WB Saunders Co;1988: 80-118.
- Turiansky GW, Benson PM, Sperling LC, et al. Phialophora verrucosa: a new cause of mycetoma. J Am Acad Dermatol. Feb 1995;32(2 pt 2):311-5. [Medline].
- Welsh O. Mycetoma. Current concepts in treatment. Int J Dermatol. Jun 1991;(6):387-98. [Medline].
- Zaias N, Taplin D, Rebell G. Mycetoma. Arch Dermatol. Feb 1969;99(2):215-25. [Medline].
Eumycetoma (Fungal Mycetoma) excerpt Article Last Updated: Oct 2, 2006
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