Mycetoma (Madura Foot): Types, Causative Agents, Clinical Features, and Lab Diagnosis

A farmer walks into a clinic with a slowly enlarging, painless swelling on his foot that has been growing for over a year. It is firm, studded with small draining openings, and grains the size of seeds ooze from them. This is mycetoma, and the single most important question the laboratory must answer is not just which organism, but whether it is a fungus or a bacterium. That one distinction decides whether the patient needs antifungal or antibacterial treatment, and getting it wrong wastes months in a disease already measured in years.

Mycetoma is an infection of the skin and subcutaneous tissues. It mainly affects the feet, but the hands, shoulder, abdomen, buttocks, and scalp infections are also reported. Mycetoma is a slowly progressive disease, and after the infection, it may take a year to form the characteristics lesions. These lesions are firm, painless, localized subcutaneous nodules.

It spreads through the surrounding tissue and, in advanced disease, can involve deeper structures including bone, though tendons and nerves are relatively spared until late. Mycetoma is also known as Madura foot or maduromycosis.

Classification of Mycetoma

Mycetoma is classified based on causative agents, the color of grains, and geographical areas.

Based on causative agents

• Eumycetoma: Mycetoma is caused by fungi.
• Actinomycetoma: Mycetoma is caused by actinomycetes.

Based on the color of grains

• Black grain mycetoma
• White or pale grain mycetoma

Most bacterial (actinomycetoma) agents produce pale grains (white to yellow), with Actinomadura pelletieri being the notable exception, producing red to pink grains. Fungal (eumycetoma) agents produce either black grains or white to pale grains, depending on the species.

Causative agent of Mycetoma

Mycetoma is caused by fungi and bacteria

Fungal agents

Fungi causing eumycetoma are saprophytic environmental fungi. Based on the formation of the grains, it is of two types:

• Black Grain Eumycetoma: These fungi form the black grains.
• White Grain Eumycetoma: These fungi form the white grains.

Bacterial agents

Actinomycetes (Gram-positive branching filamentous aerobic bacteria) causing the actinomycetoma are found in soil and environment. It gets inoculated in the body by the trauma. The color of the grains produced by actinomycetoma causing bacterial agents are given below.

Eumycetoma vs actinomycetoma

The most important step in diagnosing mycetoma is deciding whether it is fungal (eumycetoma) or bacterial (actinomycetoma), because the two look similar on the outside but need completely different treatment. The clues come together from the grains, the microscopy, and the staining.

The practical takeaway: measure the width of the filaments in the crushed grain. Broad hyphae mean a fungus (eumycetoma); thin filaments mean an actinomycete (actinomycetoma), and a positive modified acid-fast stain then points to Nocardia.

Mode of transmission of Mycetoma

The causative agents of mycetoma are present in the saprophytic soil, which gets inoculated in the body through accidental trauma. Farmers and field workers may get accidental trauma through skin abrasion and thorn pricks. Mycetoma in the head and neck occur in people who carry wood, grain bags stone on the head and neck. In rural areas, mycetoma in the ears is caused by people who use a straw to remove ear wax.

As the causative agent is introduced, the disease evolves slowly, and microabscess forms in the area of contact. The organism is also found in its center. The major feature of mycetoma infection is the presence of large aggregates of filaments of causative organisms.

Clinical features of Mycetoma

A. madurae causing foot mycetoma b) N. brasiliensis causing back mycetoma with multiple sinuses c) N. brasiliensis causing extensive mycetoma d) Fusarium solanicomplex causing tumoral mycetoma. Figure: Image source : DOI:https://doi.org/10.1371/journal.pntd.0003102.g003 a)

Mycetoma possesses occupational risk primarily to field workers and farmers. The clinical feature depends on the site of infection, lesion stage, shape, size, and color of the grains. Three important clinical features of mycetoma are:

• Tumefaction: Tumor-like swelling
• Formation of multiple discharging/draining sinuses (hollow space or cavity within the bone or tissues)
• Grains/granules discharging from sinuses

In rare cases, grains are not formed in which diagnosis is based on direct and cultural findings. Actinomadura madurae produces large grains, whereas Nocardia species produce small grains.

Laboratory diagnosis of Mycetoma

Taking the patient’s history of occupation, trauma, and geographical areas aids in the diagnosis of mycetoma.

Samples: Grains or granules are the samples of choice. Pus exudates can also be collected.

Clean the lesion with antiseptics and collect the grains by pressing the sinus from the periphery. It enhances to pass the discharge in which granules are present. Collect it in the sterile wire gauze.

Direct examination

Wash the grains in sterile saline. Crush the grains using the sterile glass rod and culture them on the suitable media.

KOH wet mount

KOH wet mount helps in observing the characteristics of the fungal structure directly

Procedure of KOH mount

Take a glass slide and add a few drops of KOH to the grains. Place the coverslip and, by applying gentle pressure, crush the grains. Use a glass rod or handle of a loop over the coverslip. Take a petri dish, put the moist filter paper and keep the slide. Leave it for a few hours. Then observe the KOH mount under the microscope.

1. Actinomycotic grains: It shows thin filaments with a diameter of 0.5 to 1 μm with coccoid or bacillary forms
2. Eumycotic grains: It shows thick 2-6 μm wide hyphae. Cells are large and swollen up to 15 μm at the margin. Chlamydospores may or may not be present in it.

To diagnose actinomycetoma, direct microscopic observation by Gram staining or acid-fast staining is done.

Gram staining shows the Gram-positive branching filamentous bacteria.

Modified Ziehl-Neelsen/ acid-fast staining (Kinyoun’s method) with 1% sulfuric acid shows Nocardia spp. i.e., reddish-pink-colored filamentous bacteria, but other actinomycetes are not acid-fast.

If septate hyphae are seen in the wet mount smear, then special staining like Hematoxylin and eosin (H&E) staining, Periodic acid-Schiff (PAS) staining, and Grocott’s Methenamine Silver (GMS) staining are done for confirmation.

Culture

After the direct observation of the crushed grains, actinomycetoma or eumycetoma is suspected. When actinomycetoma is suspected, grains samples are washed in normal saline without antibiotics and inoculated in culture media:

• Sabouraud dextrose agar without antibiotics
• Blood agar
• Lowenstein-Jensen media
• Brain-heart infusion agar

When eumycetoma is suspected, grains samples are washed in normal saline with antibiotics-streptopenicillin and penicillin. Then it is inoculated in Sabouraud dextrose agar with antibiotics like chloramphenicol and gentamicin. Modified Sabouraud dextrose agar, i.e., Emmons’ modification, is preferred.

Grains are inoculated in different plates, which increases the chances of isolation of the possible organisms and incubated at different temperatures, i.e., 25℃, 37℃, and 44℃. Then based on the cultural characteristics, causative agents are identified.

Radiodiagnosis of Mycetoma

Radiodiagnosis helps to determine the extent of the disease and study the involved tissue. X-rays, USG, CT scans, and MRI, is done. Mycetoma shows necrosis, generalized osteoporosis, and fusion of smaller bones. USG helps to differentiate eumycetoma, actinomycetoma, and non-mycetomatous lesions. MRI shows the “dot-in-circle,” which is highly specific for mycetoma.

Treatment

Treatment depends entirely on whether the mycetoma is fungal or bacterial, which is why the laboratory distinction matters so much.

Eumycetoma (fungal) is treated with systemic antifungals, principally the azoles. Itraconazole is the mainstay, and newer azoles are also used. Ketoconazole was used in the past but is now avoided for systemic treatment because of its risk of liver toxicity. Eumycetoma responds slowly and often requires prolonged therapy, sometimes combined with surgery.

Actinomycetoma (bacterial) is treated with antibacterial drugs, typically a combination such as co-trimoxazole with amikacin, given in cycles. Actinomycetoma generally responds better to medical treatment than eumycetoma.

This article gives drug-of-choice and class-level guidance only. For actual regimens, doses, and durations please consult the treating clinician.

How to Remember

Eu-mycetoma is true fungus. The prefix "eu" means true, so eumycetoma is the true-fungus form. Actinomycetoma is the actinomycete (bacterial) form.

Broad hyphae, fungus. Thin filaments, bacteria. Filament width is the fastest microscopy clue. Wide (2 to 6 μm) is fungal, thin (under 1 μm) is bacterial.

Black grains lean fungal, red grains mean Actinomadura pelletieri. Grain color narrows the list. Red or pink is the memorable exception.

Dot-in-circle points to mycetoma. On MRI, the dot-in-circle sign is highly specific for mycetoma.

Treatment follows the fork. Fungal gets antifungals, bacterial gets antibacterials. The whole diagnostic effort exists to choose between these two.

Key exam facts

Where Students Get Confused

"Eumycetoma and actinomycetoma are just two names for the same thing." No. Eumycetoma is caused by fungi, actinomycetoma by bacteria (actinomycetes). They look similar clinically but need different treatment, which is the whole reason the lab distinction matters.

"Mycetoma and actinomycosis are the same." No. Actinomycetoma is a mycetoma caused by aerobic actinomycetes such as Nocardia. Actinomycosis is a separate disease caused by anaerobic Actinomyces (usually Actinomyces israelii). Different organisms, different disease.

"Grain color alone identifies the organism." Not on its own. Grain color narrows the possibilities (red or pink strongly suggests Actinomadura pelletieri, black suggests certain fungi), but filament width, Gram stain, and acid-fast staining are needed to confirm fungal versus bacterial.

"Nocardia is a fungus because it forms filaments." No. Nocardia is a Gram-positive, branching, filamentous bacterium (an actinomycete). Its filaments are much thinner than fungal hyphae, and it is partially acid-fast.

"Mycetoma is treated with one standard drug." No. Treatment depends entirely on type. Fungal mycetoma needs antifungals, bacterial mycetoma needs antibacterials, so identifying the type is essential before treating.

References

• Chander, J. (2018). Textbook of Medical Mycology (4th ed.). Jaypee Brothers Medical Publishers.
• World Health Organization. Mycetoma (fact sheet and resources). https://www.who.int/news-room/fact-sheets/detail/mycetoma
• Larone, D. H. (2018). Larone's Medically Important Fungi: A Guide to Identification (6th ed.). ASM Press.