Britishjournal of Dermatology {1978) 99, 227.
Review
Mycetoma Mycetoma or 'Madura foot' commonly occurs in the tropics and subtropics; it is particularly prevalent in Africa, India, and Central and South America. The disease is occasionally seen in North America, but is almost unknown in Europe. A mycetoma can be defined in strict mycological terms as a concretion of fungal hyphae which form a tumour or 'fungus ball' at any site within the animal body; the term can be correctly applied therefore to fungal balls that occupy cavities in the lung as in aspergilloma. However, mycetoma (which may occur in any part of the body in the skin and subcutaneous tissues) is a recognized disease and has a much more restricted clinical meaning though caused by a wide variety of organisms. These fungi either belong to the true or higher fungi (Eumycetes), or to that group of organisms, the Schizomycetes (Actinomycetes), which are intermediate between fungi and bacteria. For practical purposes these are best classified as bacteria. Two types of mycetoma can therefore be differentiated according to the causative organisms, and such a division is pertinent to the management ofthe patient. (a) Actinomycetoma: this is caused by the aerobic Schizomycetes such as Nocardia and Streptomyces. (b) Eumycetoma: this is caused by the Eumycetes (true fungi) such as Madurella and Cephalosporium. Both the Eumycetoma and the Actinomycetoma present with similar clinical manifestations. The process usually affects the feet (Fig. i) but may affect the legs, the arms and shoulders, or the head. Characteristically there is swelling ofthe affected area with multiple draining sinus tracts that exude pus containing granules of varying size and colour. Laboratory examination of these granules not only confirms the clinical diagnosis but may also determine the type of mycetoma, and thus the mode of treatment. Mycetoma is usually seen in men in the third and fourth decades and minor injuries serve as a portal of entry for the infecting organisms which are saprophytes of soil and plants. Consequently the feet are the most frequently aifeaed sites and this explains the synonym 'Madura foot'. The incubation period varies from one week to several months. The disease is not contagious from man to man, or from animals to man. Usually the condition begins as a painless nodule at the site of previous trauma; indeed the absence of pain is characteristic throughout the course of the complaint. This primary nodule softens and discharges pus. Subsequently the whole foot swells to such an extent as to cause the sole to assume a convex surface and the lesions extend deeply into subcutaneous tissue. Multiple secondary nodules develop and these suppurate and drain through multiple sinus tracts exuding a serous, sero-sanguinous, or purulent discharge in which pigmented granules may be found, especially during exacerbations. The colour of the granules varies according to the causative organism and so visual examination of the pus is the first step to the laboratory diagnosis. The infection remains localized and constitutional disturbance is rare but when it does occur it generally results from secondary bacterial infections ofthe open sinus tracts. In chronic cases the sinuses may extend deeply into the muscle and bone. Osteomyelitis may be marked and is readily detectable on X-ray which shows evidence of periostitis and cavities within the bone (Fig. 2). Mycetoma ofthe abdomen may present difficulties diagnostically because of similarities to appendicitis. However, the correct diagnosis should be apparent when discharging sinuses are seen in the abdominal wall. 0007-0963/78/0800-0227 $02.00 © 1978 British Association of Dermatologists 227
228
FIGURE 1. Mycetoma of foot, showing swelling of foot and multiple sinuses exuding pus. DIAGNOSIS
At present the laboratory investigations are concerned with the exudate alone as serological tests are still only of academic value. However, serological tests may well in future become incorporated as a routine procedure for the specific identification of the aetioiogical agent. The mycological diagnosis is deduced from direct observation and from culture of the granules or pus. (a) Direct observation. The presence and colour of the granules should be recorded and may well suggest the causative orgatusm (see Table i). Dark coloured granules are readily found but white to cream coloured granules can be difficult to recognize. Thick pus should be diluted with physiological saline and spread out in a suitable receptacle. Granules appear as discrete opaque bodies of roundish shape with a lobulated smooth shiny surface. To enable microscopic examination, the granule should first be crushed and then motuited in a drop of 2O'\i potassium hydroxide (KOH). A Gram stained smear should also be made. The hyphae from eumycetomas appear as broad septate branching filaments which frequently form chiainydospores in the peripheral region of the granule. They stain poorly but are generally considered to be Gram positive. Granules from actinomycetomas are composed of extremely fine hyphae (about I (im wide) and these may be difficult to see in the KOH preparation. The stained film reveals delicate Gram positive branching filaments which may or may not end in a club shape in the peripheral region of the granule. Short bacillary elements may also be seen. Where no granules are found the pus should be examined by the same procedtires. The direct observations carried out on the exudate enable the type of mycetoma to be ascertained and so the correct method of therapy can be instituted in most instances before the results of culture are known.
Review
229
FIGURE 2. X rays of mycetoma of foot, showing multiple lesions in metatarsals producing irregular expansion and destruction of bone. There is also sofi tissue swelling and calciiieation.
TABLE I. Species commonly associated with mycetoma Type of mycetoma Actinomycetoma
Colour of granules White to yellowish
Yellow to brownish Bright red Black Eumycetoma
White to yellowish
Yellow to brownish Brown to black Black
Species Nocardia asteroides Nocardia brasiliensis Nocardia caviae Streptomyces madurae Streptomyces somaUensis Streptomyces pelletieri Streptomyces paraguayensis Monosporiuin apiospermurn (Allescheria boydii) Cephalosporium falciforme Cephalosporium redfei Neostudina rosati Phialophora jeariselmei Madurella mycetomi Madurella grisea Leptosphacria seyiegalensis Pvrenochacta romcroi
230
"
Review
(b) Culture. In order to reveal the specific identity ofthe fiingus or bacteria the specimen has to be cultured. Isolation ofthe causative organism will also allow drug sensitivities to be determined where applicable. Since the surface is likely to be heavily contaminated the granules should be washed several times in sterile physiological saline. They should then be crushed in saline and the resultant suspension provides a suitable inoculum for streaking onto agar media. In eumycetoma, a plate containing Sabouraud's medium with antibacterial antibiotics (though not with cycloheximide as this is inhibitory to a number of species causing mycetoma) should be inoculated and left for at least 3 weeks at 37 C, and one containing Littman ox-gall agar, should also be inoculated and kept for this time at 25-30 C before being discarded. Any bacteriological medium will support the growth of organisms causing actinomycetoma but beef heart infusion blood agar tends to be the preferred medium. A Petri dish containing this medium and one containing Sabouraud's agar without antibiotics should be incubated at 37 C. A duplicate set of plates should be incubated at 25-27C. Again the plates should be retained for about 3 weeks. The organisms are identified according to specific characteristics and the more common isolates are listed in Table i. Because the specimen is prone to contamination it may be necessary to isolate a species on several occasions before pathogenicity can be ascribed. The clinical investigations should include X-ray of the affected area to determine the presence and extent of osteomyelitis; this may be a useful prognostic indication in the drug therapy of actinomycetoma.
TREATMENT
The correct treatment of mycetoma depends to a considerable extent on the causative organism. In general an actinomycetoma may be amenable to conservative treatment, whereas a eumycetoma will only be ameliorated by surgical intervention. In a recent series Mahgoub (1976) reported a 60*^,) 'cure rate' in actinomycetoma^using'either a combination of dapsone and streptomycin, or cotrimoxazole and streptomycin. Unfortunately the report does not mention the long term follow-up as patients on such drug regimes can show significant recurrence rates after the cessation of therapy. In eumycetoma various antifungal agents have been tried but with little success; this is perhaps surprising as the fungi causing eumycetoma are low grade pathogens and so their eradication should be readily achieved by administration of a safe systetnically active agent. However, as in the case of aspergilloma in lung tissue, it seems that therapeutic levels of the drug within the lesion are not attainable, probably due to poor blood supply to such areas. For this reason local injections of amphotericin B (Costello et ai, 1959; Mathews et al., 1968) may prove worthy of evaluation. The newly discovered antifungal imidazoles may also prove useful in the future but the cost of such treatment will prevent widespread use in the 'Third World'. In the meantime, for eumycetoma and for recurrent actinomycetoma, the most effective treatment is surgical excision of the affected area. This treatment may seem drastic, but ultimately the patient will be less crippled by a below-knee amputation and a prosthesis than by retention of a swollen diseased foot. Department of Dermatology, Royal Infirmary and Mycology Unit, Western General Hospital, Edinburgh
R.StC.BARNHTSON L.J.R.MlLNE
Review
231
REFERENCES COSTELLO, M.J., DEFEO, C .P . & LITTMAN, M.L. (1959) Chromoblastomycosis treated with local infiltration of Amphotericin B solution. Archives of Dermatology, 79, 184. MAHGOxre, E.S. (1976) Medica] management of mycetoma. Bulletin of the World Health Organisation, 54, 303. MATHEWS, R.S., BUCKLEY, C.E., NEILSON, H.S., GRANT, A.J. & EDWARDS, W . (1968) Local chemotherapy of
deepseated fungus infections; maduromycosis of the foot. Clinical Research, 16, 48.
Review
Mycetoma Mycetoma or 'Madura foot' commonly occurs in the tropics and subtropics; it is particularly prevalent in Africa, India, and Central and South America. The disease is occasionally seen in North America, but is almost unknown in Europe. A mycetoma can be defined in strict mycological terms as a concretion of fungal hyphae which form a tumour or 'fungus ball' at any site within the animal body; the term can be correctly applied therefore to fungal balls that occupy cavities in the lung as in aspergilloma. However, mycetoma (which may occur in any part of the body in the skin and subcutaneous tissues) is a recognized disease and has a much more restricted clinical meaning though caused by a wide variety of organisms. These fungi either belong to the true or higher fungi (Eumycetes), or to that group of organisms, the Schizomycetes (Actinomycetes), which are intermediate between fungi and bacteria. For practical purposes these are best classified as bacteria. Two types of mycetoma can therefore be differentiated according to the causative organisms, and such a division is pertinent to the management ofthe patient. (a) Actinomycetoma: this is caused by the aerobic Schizomycetes such as Nocardia and Streptomyces. (b) Eumycetoma: this is caused by the Eumycetes (true fungi) such as Madurella and Cephalosporium. Both the Eumycetoma and the Actinomycetoma present with similar clinical manifestations. The process usually affects the feet (Fig. i) but may affect the legs, the arms and shoulders, or the head. Characteristically there is swelling ofthe affected area with multiple draining sinus tracts that exude pus containing granules of varying size and colour. Laboratory examination of these granules not only confirms the clinical diagnosis but may also determine the type of mycetoma, and thus the mode of treatment. Mycetoma is usually seen in men in the third and fourth decades and minor injuries serve as a portal of entry for the infecting organisms which are saprophytes of soil and plants. Consequently the feet are the most frequently aifeaed sites and this explains the synonym 'Madura foot'. The incubation period varies from one week to several months. The disease is not contagious from man to man, or from animals to man. Usually the condition begins as a painless nodule at the site of previous trauma; indeed the absence of pain is characteristic throughout the course of the complaint. This primary nodule softens and discharges pus. Subsequently the whole foot swells to such an extent as to cause the sole to assume a convex surface and the lesions extend deeply into subcutaneous tissue. Multiple secondary nodules develop and these suppurate and drain through multiple sinus tracts exuding a serous, sero-sanguinous, or purulent discharge in which pigmented granules may be found, especially during exacerbations. The colour of the granules varies according to the causative organism and so visual examination of the pus is the first step to the laboratory diagnosis. The infection remains localized and constitutional disturbance is rare but when it does occur it generally results from secondary bacterial infections ofthe open sinus tracts. In chronic cases the sinuses may extend deeply into the muscle and bone. Osteomyelitis may be marked and is readily detectable on X-ray which shows evidence of periostitis and cavities within the bone (Fig. 2). Mycetoma ofthe abdomen may present difficulties diagnostically because of similarities to appendicitis. However, the correct diagnosis should be apparent when discharging sinuses are seen in the abdominal wall. 0007-0963/78/0800-0227 $02.00 © 1978 British Association of Dermatologists 227
228
FIGURE 1. Mycetoma of foot, showing swelling of foot and multiple sinuses exuding pus. DIAGNOSIS
At present the laboratory investigations are concerned with the exudate alone as serological tests are still only of academic value. However, serological tests may well in future become incorporated as a routine procedure for the specific identification of the aetioiogical agent. The mycological diagnosis is deduced from direct observation and from culture of the granules or pus. (a) Direct observation. The presence and colour of the granules should be recorded and may well suggest the causative orgatusm (see Table i). Dark coloured granules are readily found but white to cream coloured granules can be difficult to recognize. Thick pus should be diluted with physiological saline and spread out in a suitable receptacle. Granules appear as discrete opaque bodies of roundish shape with a lobulated smooth shiny surface. To enable microscopic examination, the granule should first be crushed and then motuited in a drop of 2O'\i potassium hydroxide (KOH). A Gram stained smear should also be made. The hyphae from eumycetomas appear as broad septate branching filaments which frequently form chiainydospores in the peripheral region of the granule. They stain poorly but are generally considered to be Gram positive. Granules from actinomycetomas are composed of extremely fine hyphae (about I (im wide) and these may be difficult to see in the KOH preparation. The stained film reveals delicate Gram positive branching filaments which may or may not end in a club shape in the peripheral region of the granule. Short bacillary elements may also be seen. Where no granules are found the pus should be examined by the same procedtires. The direct observations carried out on the exudate enable the type of mycetoma to be ascertained and so the correct method of therapy can be instituted in most instances before the results of culture are known.
Review
229
FIGURE 2. X rays of mycetoma of foot, showing multiple lesions in metatarsals producing irregular expansion and destruction of bone. There is also sofi tissue swelling and calciiieation.
TABLE I. Species commonly associated with mycetoma Type of mycetoma Actinomycetoma
Colour of granules White to yellowish
Yellow to brownish Bright red Black Eumycetoma
White to yellowish
Yellow to brownish Brown to black Black
Species Nocardia asteroides Nocardia brasiliensis Nocardia caviae Streptomyces madurae Streptomyces somaUensis Streptomyces pelletieri Streptomyces paraguayensis Monosporiuin apiospermurn (Allescheria boydii) Cephalosporium falciforme Cephalosporium redfei Neostudina rosati Phialophora jeariselmei Madurella mycetomi Madurella grisea Leptosphacria seyiegalensis Pvrenochacta romcroi
230
"
Review
(b) Culture. In order to reveal the specific identity ofthe fiingus or bacteria the specimen has to be cultured. Isolation ofthe causative organism will also allow drug sensitivities to be determined where applicable. Since the surface is likely to be heavily contaminated the granules should be washed several times in sterile physiological saline. They should then be crushed in saline and the resultant suspension provides a suitable inoculum for streaking onto agar media. In eumycetoma, a plate containing Sabouraud's medium with antibacterial antibiotics (though not with cycloheximide as this is inhibitory to a number of species causing mycetoma) should be inoculated and left for at least 3 weeks at 37 C, and one containing Littman ox-gall agar, should also be inoculated and kept for this time at 25-30 C before being discarded. Any bacteriological medium will support the growth of organisms causing actinomycetoma but beef heart infusion blood agar tends to be the preferred medium. A Petri dish containing this medium and one containing Sabouraud's agar without antibiotics should be incubated at 37 C. A duplicate set of plates should be incubated at 25-27C. Again the plates should be retained for about 3 weeks. The organisms are identified according to specific characteristics and the more common isolates are listed in Table i. Because the specimen is prone to contamination it may be necessary to isolate a species on several occasions before pathogenicity can be ascribed. The clinical investigations should include X-ray of the affected area to determine the presence and extent of osteomyelitis; this may be a useful prognostic indication in the drug therapy of actinomycetoma.
TREATMENT
The correct treatment of mycetoma depends to a considerable extent on the causative organism. In general an actinomycetoma may be amenable to conservative treatment, whereas a eumycetoma will only be ameliorated by surgical intervention. In a recent series Mahgoub (1976) reported a 60*^,) 'cure rate' in actinomycetoma^using'either a combination of dapsone and streptomycin, or cotrimoxazole and streptomycin. Unfortunately the report does not mention the long term follow-up as patients on such drug regimes can show significant recurrence rates after the cessation of therapy. In eumycetoma various antifungal agents have been tried but with little success; this is perhaps surprising as the fungi causing eumycetoma are low grade pathogens and so their eradication should be readily achieved by administration of a safe systetnically active agent. However, as in the case of aspergilloma in lung tissue, it seems that therapeutic levels of the drug within the lesion are not attainable, probably due to poor blood supply to such areas. For this reason local injections of amphotericin B (Costello et ai, 1959; Mathews et al., 1968) may prove worthy of evaluation. The newly discovered antifungal imidazoles may also prove useful in the future but the cost of such treatment will prevent widespread use in the 'Third World'. In the meantime, for eumycetoma and for recurrent actinomycetoma, the most effective treatment is surgical excision of the affected area. This treatment may seem drastic, but ultimately the patient will be less crippled by a below-knee amputation and a prosthesis than by retention of a swollen diseased foot. Department of Dermatology, Royal Infirmary and Mycology Unit, Western General Hospital, Edinburgh
R.StC.BARNHTSON L.J.R.MlLNE
Review
231
REFERENCES COSTELLO, M.J., DEFEO, C .P . & LITTMAN, M.L. (1959) Chromoblastomycosis treated with local infiltration of Amphotericin B solution. Archives of Dermatology, 79, 184. MAHGOxre, E.S. (1976) Medica] management of mycetoma. Bulletin of the World Health Organisation, 54, 303. MATHEWS, R.S., BUCKLEY, C.E., NEILSON, H.S., GRANT, A.J. & EDWARDS, W . (1968) Local chemotherapy of
deepseated fungus infections; maduromycosis of the foot. Clinical Research, 16, 48.
