Myzetome B47.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Eumyzetome; Indian fungus; Madura Foot; Maduramycosis; Madura mycosis; Mycetoma; Phycomycetome

History
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Gill, 1842; Godfrey 1846; Carter, 1861

Definition
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Indolent, chronic granulomatous infection of the skin and subcutis (myceteomas are only found on the skin!) with circumscribed, tumour-like, sometimes monstrous, purulent swellings (pseudotumour), mostly with fistulae and characteristic formation of granules (grains, drusen), which are expelled to the outside by fistula ducts. In case of an infestation of the feet one speaks of "Madura foot".

Pathogen
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Myzetomes are caused by fungi (eumyzetome) or fungal bacteria (actinomycetome). Based on the colour of the granules typical for the disease group, the following pathogens can be deduced:

  • For black granules (caused by black fungus): Madurella mycetomi, Madurella grisei, Leptosphaeria senegalensis, Pyrenochaeta romeroi.
  • For light-coloured granules: Allescheria boydii, Cephalosporium falciforme or Cephalosporium recifei.
  • Also: Nocardia brasiliensis ( Nocardiosis)
  • in rare cases dermatophytes.

Classification
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A distinction is made according to the pathogen and the colour of the granules:

  • Eumycetomes:
    • Pathogens are, for example: Madurella grisea and mycetomatis, Aspergillus spp., Acremonium spp., Leptosphaeria spp, Pseudallescheria spp. Fusarium solani; Exophiala jeanselmei, Sarocladium kiliense, Acremonium blochii, Aspergillus nidulans, Fusarium incarnatum, Scedosporium apiospermum complex, Curvularia lunata, Medicopsis romeroi (Dubey N et al. 2019).
    • Very rare are reports of mycetomes by dermatophytes (e.g. Trichophyton tonsurans).
  • Actinomycetomes (actinomyotic myceteomes):
    • Radiation bacteria like actinomyces, Nocardia, Streptomces.
  • Schizomycetomes or "botromycotic mycetomes" (Staphylococcus spp., Escherichia coli, Proteus spp., etc.).

Occurrence/Epidemiology
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Myzetomes are a rarity in Europe, but they are endemic in India and South America. Furthermore, they can be found in the tropical and subtropical countries of Africa (Myzetome belt between the 15th and 30 degrees northern latitude/Senegal-Sudan). Eumycetomes and actinomycetomes are distributed differently: in Mexico there are mainly actinomycetomes, in Africa eumycetomes.

Males are 5 times more frequently affected than females.

Preferably occurs in exposed rural populations by walking barefoot.

Etiopathogenesis
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Penetration of the pathogens through small skin injuries(injury mycosis) mostly when walking barefoot (lower extremity is the typical localization). Pathogens that colonize spines or other parts of plants are inoculated into the skin. Mycetomas caused by dermatophytes (e.g. Trichophyton mentagrophytes var. interdigital) usually develop under immunosuppression.

Localization
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Mainly occurring on the feet (Madura foot) (70%), less frequently hands are affected; rarities are found in other parts of the body (abdomen, face, oral cavity). The first lesion is usually found between the 1st and 2nd metatarsal bone.

Clinical features
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Initially, after a mostly (for months past) unnoticed injury, a 0.2-0.5 cm large, not painful, subcutaneous, firm, skin-coloured induration is found on one side of the sole of the foot, between the 1st and 2nd metatarsal bone (injury mycosis). In the following months the infection spreads to the subcutis of the foot, recognizable by the increasing solid induration of the affected area. The overlying skin initially remains freely movable. Later, painless nodules (pseudotumours) develop. Abscess formation and fistula tracts with emptying of light or black granulae (drusen/grains = microcolonies) occur.

The infection can spread from the skin over years. As the muscles, nerves and tendons remain resistant to the infection for a long time, the function of the foot is maintained for a long time! Regional lymph nodes may be enlarged. A hematogenous sowing of the pathogens is omitted.

The progression takes place per continuitatem also on tendons, muscles and bones. The process ultimately becomes painful and leads to functional limitations. Internal organs are otherwise not involved! Characteristic are fistula openings in the shapelessly swollen extremity, from which pus empties under pressure.

Mycetomas are not accompanied by systemic reactions such as fever, leukocytosis, anaemia or weight loss. Little is known about a systemic immune response.

Histology
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Formation of cutaneous and subcutaneous abscesses. Pathogens are detectable in the form of microcolonies (drusen). These consist of dense clusters of pathogens and appear clinically as visible granulae in the abscess side. In older foci, granulomatous epitheloid cell reactions with giant cells occur.

Diagnosis
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Typical clinic for patients with a correspondingly disposition and a long course over many years. Localization!

Detection of the 0.1-0.5 cm large, differently coloured drusen (recognisable as granules) in the fistula fluid.

Microscopic or cultural pathogen detection (see mycoses below).

Radiological changes are only detectable in a late phase of the disease. Nuclear spin examinations are better suited to detect early changes. A typical sign of a "dot in circle" is a 0.2-0.5 cm hyperintense lesion surrounded by fibrosed tissue.

Differential diagnosis
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  • Endemic Kaposi sarcoma: Histology is conclusive.
  • Charcot foot ( arthropathy, Charcot arthropathy): Polyneuropathic, chronic, mutating joint disease, as a late complication of diabetes mellitus (especially in diabetic polyneuropathy).
  • Osteomyelitis: Pathogen detection
  • Tuberculosis: Pathogen detection
  • Botryomycosis: Also detection of granulae. Kinematic picture very similar, but systemic infestation. Common in immunosuppressed patients: HIV infection, diabetes mellitus, immunosuppressive therapy, cystic fibrosis, osteomyelitis. Pathogen detection.
  • Spinocellular carcinoma: Histology is conclusive.

Complication(s)
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Bacterial superinfection, bone destruction, adenopathy, visceral and cerebral metastases.

Therapy
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Early diagnosis and immediate treatment are important to avoid bone involvement and the amputation that is almost always associated with it.

Internal therapy
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  • Actinomycetoma: Antibiosis after antibiogram. Bacterially induced myceteomas are generally easier to control than eumycetomas. Therapy with streptomycin sulfate and dapsone has proven to be effective; alternatively streptomycin sulfate and trimethoprim/sulfmethoxazole.
  • Eumycetomes: Ketoconazole (e.g. Nizoral 400 mg/day) shows the best results, especially in infections with Madurella mycetomatis. Therapy duration: Months to years (beyond healing), depending on the pathogen also in combination with antibiotics. Resistances are frequent in Pseudoallescheria boydii or Acremonium species. In selected cases antimycotics such as itraconazole (e.g. Sempera) or griseofulvin (e.g. grivulvin) and terbinafine (high dosage of 1000 mg/day p.o.) are useful. Also with Terbinafine in high dosage (1000mg/day p.o.) satisfactory results could be achieved. Eumycetomas are difficult to treat overall and usually require long-term therapy.
  • Posaconazole: In case of resistance to therapy or patients with intolerance to other systemic antimycotics: 2 times/day 400 mg (10 ml) p.o. (daily dose: 800 mg) or 4 times/day 200 mg (5 ml) p.o. The duration of therapy depends on the severity of the disease, recovery from immunosuppression and clinical response, if applicable.
  • Schizomycetomas: antibiotics depending on the resistance status.

Operative therapie
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Surgical excision, possibly removal of fistula ducts and drainage. In endemic areas, a generous amputation is recommended in case of bone involvement (due to the often unaffordable therapeutic costs of pharmacotherapy) if there is a strong tendency to spread.

Progression/forecast
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Awkward. Invalidity and death of a patient with internal organs.

Note(s)
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Originally, the term "Myzetom" was only understood to mean a fungal infection. However, it is common to include anatomically similar infections caused by bacteria under this term as well.

Literature
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  1. Aamir S et al (2003) Mycetoma caused by Scytalidium dimidiatum. Br J Dermatol 148: 174-176
  2. Ballingalli GR (1855) An account of a tumor affecting the foot. Trans Med Phy Soc Bombay 2(ns): 273-276
  3. Bonifaz A et al (2007) Mycetoma in children: Experience with 15 cases. Pediatric Infect Dis J 26: 50-52
  4. Carter HV (1861) Mycetoma or the fungus disease of India including notes of recent cases and new observations on the structure etc. of the entophytic growth. Trans Med Phy Soc Bombay 7: 206-221
  5. Douwes KE et al (2003) Branched filaments no fungus, ovoid bodies no bacteria: Two unusual cases of mycetoma. J Am Acad Dermatol 49: S170-173
  6. Dubey N et al (2019) Epidemiological profile and spectrum of neglected tropical disease eumycetomafrom
    Delhi, North India.Epidemiol Infect 147:e294.
  7. Gill (1842) Indian Naval Medical Reports - quoted by Ghosh LM, et al. Madura foot (mycetoma). Indian Medical Gazette 85: 288
  8. Gugnani HC (2002) Nocardia asteroides' mycetoma of the foot. J Eur Acad Dermatol Venereol 16: 640-642
  9. Greenberg AK (2002) Clinical presentation of pulmonary mycetoma in HIV-infected patients. Chest 122: 886-892
  10. Hattori Y (2003) Nocardia africana isolated from a feline mycetoma. J Clin Microbiol 41: 908-910
  11. Honraet K et al (2005) Recurrent colonization of successively implanted tracheoesophageal vocal prostheses by a member of the Fusarium solani species complex. J Clin Microbiol 43: 770-777
  12. Khatri ML (2002) Mycetoma in Yemen: clinicoepidemiologic and histopathologic study. Int J Dermatol 41: 586-593
  13. Nenoff P et al (2015) Tropical and travel-associated dermatomycoses. Part 2: Cutaneous infections through yeast pizzles. Molds and dimorphic fungi. Dermatologist 66: 522-532
  14. Pinoy E (1913) Actinomycoses and Mycetomes. Bull Inst. Pasteur 11: 977-984
  15. Prabhakaran S et al (2005) Isolated primary intracerebral mycetoma: presenting as a mass lesion in a patient with prostate cancer and multiple myeloma. J Neurooncol 71: 49-52
  16. Yera H (2003) Mycetoma of the foot caused by Fusarium solani: identification of the etiologic agent by DNA sequencing. J Clin Microbiol 41: 1805-1808

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Last updated on: 29.10.2020