Eumycetoma (Fungal Mycetoma) 

Updated: Oct 19, 2017
Author: George Turiansky, MD; Chief Editor: Dirk M Elston, MD 

Overview

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 people 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.[1] 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.[2]

Note: 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.

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.

Etiology

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 with a white-to-yellow granule that cause eumycetoma include the following:

  • Acremonium species

  • Aspergillus nidulans

  • Aspergillus flavus

  • Cylindrocarpon cyanescens

  • Cylindrocarpon destructans

  • Fusarium species

  • Neotestudina rosatii

  • Polycytella hominis

  • P boydii

Fungi with a black granule that cause eumycetoma include the following:

  • Cladophialophora bantiana[3]

  • Corynespora cassicola

  • Curvularia species

  • Exophiala jeanselmei

  • L senegalensis

  • L tompkinsii

  • M grisea

  • M mycetomatis

  • Phialophora verrucosa[4]

  • Plenodomus auramii

  • Pyrenochaeta mackinnonii

  • Pyrenochaeta romeroi[5]

Epidemiology

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.[6] 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,[7] Senegal, Somalia, Nigeria, Zaire, Chad), Pakistan, Yemen, Mexico, Central America, South America (eg, Guatemala, Venezuela, Colombia, Brazil), and Indonesia.

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.

Prognosis

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.

 

Presentation

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 Examination

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 below).

Eumycetoma of the leg with tumefaction, deformity, 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.
Eumycetoma of the foot with tumefaction, deformity Eumycetoma of the foot with tumefaction, deformity, and multiple sinus tracts. Courtesy of Mervyn L. Elgart, MD, Washington, DC.

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.

 

DDx

 

Workup

Laboratory 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.[8, 9]

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.

Ahmed et al reported two cases of leg eumycetoma due to M mycetomatis that were successfully identified by species-specific polymerase chain reaction and DNA sequencing.

Fine-needle aspiration cytology of lesional tissue with the use of special stains may be useful in diagnosis.[10]

Imaging Studies

Radiographs, CT scans, and MRIs demonstrate the presence and extent of bone or organ involvement.[11] 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.

 

Treatment

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.[12] 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.[13, 14]

One 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.[15]

A 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.[16]

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. A 2017 review of 13 eumycetoma cases with or without bony involvement showed promising results with surgical treatment combined with itraconazole monotherapy or with itraconazole combined with amphotericin or fluconazole, with a variable recurrence rate in some.[17]

Long-Term Monitoring

A prolonged follow-up period is necessary to monitor for disease recurrence.

 

Medication

Medication Summary

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.

Antifungal Agents

Class Summary

Reportedly, imidazole antifungal agents are variably effective in the treatment of eumycetoma when they are used alone or in conjunction with surgical therapy.

Ketoconazole (Nizoral)

Ketoconazole is a synthetic imidazole antifungal agent. It is a broad-spectrum agent known to be a potent inhibitor of the cytochrome P-450 3A4 enzyme system in vitro. Inhibition of this system impairs the synthesis of ergosterol, a vital component of fungal cell membranes.

Itraconazole (Sporanox)

Itraconazole is a triazole antifungal agent known to be a potent inhibitor of the cytochrome P-450–dependent synthesis of ergosterol in vitro. It slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.