Mycetoma

• Chronic progressive granulomatous implantation infection of the skin and subcutaneous tissue, usually affecting a single extremity
• Caused by either fungi or fungal-like bacteria

Background

Microbiology

• Can be caused either by fungi or filamentous aerobic bacteria
• Fungal species (eumycotic mycetoma):
  • Dark grains:
    • Madurella mycetomatis
    • Leptosphaeria senegalensis
    • Madurella grisea
    • Exophiala jeanselmei and Exophiala oligosperma
  • Pale/white grains:
    • Pseudallescheria boydii (most common) (Scedosporium)
    • Acremonium kiliense
    • Aspergillus flavus, Aspergillus nidulans, Aspergillus hollandicus
• Aerobic bacteria (actinomycotic mycetoma):
  • Nocardia brasiliensis
  • Actinomadura madurae
  • Streptomyces somaliensis
  • Actinomadura pelletieri (grains are red to pink)

Epidemiology

• Present worldwide between 15ºS and 30ºN
• Within Latin America, Mexico has the highest incidence
• Also relatively high incidence in Chad, Ethiopia, India, Mauritania, Senegal, Somalia, Sudan, Yemen, and Venezuela
• More common in poorer, rural communities

Clinical Presentation

• Chronic implantation fungal infection characterized by swelling and draining sinuses
• Can involve deeper tissues such as muscle or bone (in contrast to chromoblastomycosis)
• Clinical triad:
  • Localized swelling
  • Underlying sinus tract
  • Grains and granules (“sulfur granules”) within the sinus tracts
• May spread via lymphatics in a sporotrichoid pattern

Comparison of eumycetoma and actinomycetoma

	Eumycetoma	Actinomycetoma
Location	Africa and India	Latin America
Patients	20 to 40 years old	40 to 50 years old
Distribution	Predominantly feet
Progression	Less aggressive	More aggressive
Clinical features	Few fistulae with proliferative sinuses, late bone involvement with large bone cavities	Many fistulae with flat sinuses, early bone involvement with small bone cavities

Differential Diagnosis

• Spororichosis
• Yaws
• Non-tuberculous mycobacteria
• Tuberculosis
• Osteomyelitis
• Syphilitic osteitis
• Neoplasms, including Kaposi sarcoma, fibroma, neurofibroma, malignant melanoma, fibrolipoma, osteosarcoma, rhabdomyosarcoma, osteogenic sarcoma
• Other non-infectious causes, including foreign body granulomatous reaction and bone cysts

Diagnosis

• Specimen collection
  • Send granules in sterile container
  • Can do skin scraping in areas of moist or broken skin
  • Skin biopsy
• Histology/microscopy
  • Gram stain a crushed granule for bacteria
• Culture
  • Set up cultures for bacterial and fungal culture

Management

• May need imaging to assess severity and help plan management1
  • Ultrasound is the most commonly used
  • CT and MRI may also be helpful
• Actinomycetoma can be managed medically
  • Standard treatment is trimethoprim-sulfamethoxazole 48 mg/kg per day for 5 weeks followed by amikacin 15 mg/kg daily divided q12h for 3 weeks, followed by a 2 week interval, then repeated until cured (usually four cycles)
    • May substitute amoxicillin-clavulanic acid for the trimethoprim-sulfamethoxazole
    • Rescue therapies substitute in a carbapenem for the trimethoprim-sulfamethoxazole
  • Can also try combination trimethroprim-sulfamethoxazole plus either dapsone or streptomycin
• Eumycetoma is more difficult to treat, and usually requires medical management for months to a year, followed by wide local excision of the lesions
  • Antifungals should be targetted to the causative organism, or empirically against Madurella mycetomatis
  • Recommended empiric treatment is with itraconazole 200 to 400 mg/day for 6 to 9 months
  • Can also try ketoconazole 400 to 800 mg/day for 9 to 12 months or terbinafine
  • Treatment shrinks but does not necessarily cure the lesions

Further Reading

• Mycetoma: a unique neglected tropical disease. Lancet Infect Dis. 2016;16(1):100-112. doi: 10.1016/S1473-3099(15)00359-X