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EL MICETOMA
El micetoma es una enfermedad infecciosa granulomatosa crónica que afecta la piel, el tejido subcutáneo y, a veces, el hueso. Es causada por hongos filamentosos (eumicetoma) o bacterias (actinomicetoma).
El micetoma que antes se creía era una enfermedad típica de regiones tropicales y subtropicales, ha sobrepasado estas áreas encontrándose para el año 2019 mas de 19.000 mil casos en 102 países des 1876 hasta 2019, siendo reportado en: México, Sudán, Venezuela, Brasil, Estados Unidos, China, Italia, Bulgaria, Alemania, Países Bajos, Portugal, Eslovenia, España, Reino Unido, Albania, Turquía, Australia, India, Pakistán Egipto, Chad, Etiopía, Mauritania, Yemen, (Asia y países africanos).
Para 2024 los países con mayor número de casos son México y Sudán.
AGENTES CAUSALES:
En el caso del eumicetoma (Hongos) las especies más comunes incluyen Madurella mycetomatis, Pseudallescheria boydii y Acremonium.
El actinomicetoma (Bacterias) está frecuentemente asociado con Nocardia brasiliensis, aunque también pueden estar involucradas otras especies como Actinomadura y Streptomyces.
En Venezuela, la enfermedad predomina en la región Centro occidental del país, en los estados Lara y Falcón. También se han encontrados casos en las regiones: Central del Estado Zulia y de Guayana. Los agentes más frecuentemente aislados en el Estado Falcón son Actinomadura madurae y Nocardia brasiliensis.
Otros agentes causales reportados en venezuela son: Aspergillus ustus, Cyphellophora oxyspora, Exophiala oligosperma, Madurella pseudo mycetomatis, Nocardia farcinica and Nocardia wallacei.
Para el Eumicetoma en Venezuela, los principales agentes etiológicos son: Pyrenochaeta mackinonnii (32%), P. romeroi (24%) y Madurella grisea (20%
MANIFESTACIONES CLÍNICAS:
La enfermedad se caracteriza por la formación de hinchazones tumorales, trayectos sinusales y la secreción de granos que contienen los organismos causantes.
El micetoma es endémico en las regiones tropicales y subtropicales, pero puede aparecer esporádicamente en climas templados.
El pie es el sitio más comúnmente afectado (79% de los casos), a menudo denominado "pie de Madura", pero puede afectar cualquier parte del cuerpo. Los organismos causantes generalmente ingresan al cuerpo a través de un traumatismo cutáneo menor, como un pinchazo de espinas (arbustos de zonas tropicales y subtropicales). La triada clásica del micetoma incluye una masa subcutánea indolora, fístulas con secreción y la presencia de granos.
La enfermedad se ha observado en niños de 3 años de edad y en individuos de 80 años, pero predomina entre la 2a década de la vida. Es más común en hombres que en mujeres (2 a 1), y predomina en campesinos, afectando principalmente los miembros inferiores, siendo el pie el órgano mayor afectado como se explico previamente.
DIAGNÓSTICO:
El diagnóstico implica evaluación clínica, examen de los granos, microscopía, imágenes (p. ej., radiografía, resonancia magnética) y cultivo. Los métodos moleculares como la PCR y la secuenciación se utilizan cada vez más para una identificación rápida y precisa, especialmente en casos con cultivos negativos.
TRATAMIENTO:
El tratamiento varía según si el micetoma es actinomicetoma o eumicetoma:
Para el eumicetoma, los antifúngicos como itraconazol o ketoconazol son comúnmente utilizados. Se recomienda un régimen de 200 a 400 mg diarios durante un período prolongado (generalmente seis meses).
También se han utilizado el Fluconazol, Fosruvoconazole y anfotericina B para el tratamiento del eumicetoma.
El eumicetoma es más difícil de tratar, y a menudo requieren una administración prolongada y no siempre son efectivos. La intervención quirúrgica, incluida la amputación, puede ser necesaria en casos graves.
El actinomicetoma generalmente responde mejor a los antibióticos, como el cotrimoxazol (trimetoprim-sulfametoxazol) y la amikacina. Al igual que en el Eumicetoma los casos graves pueden necesitar cirugía.
Otros antibióticos utilizados son: minociclina, amoxicilina, rifampicina, diamino-difenil-sulfona (DDS) y estreptomicina.
MEDIDAS PREVENTIVAS:
Las medidas preventivas incluyen el uso de ropa y calzado protectores, especialmente en áreas endémicas. El diagnóstico y el tratamiento tempranos son cruciales para prevenir complicaciones y discapacidad.
Saludos,,,
Dr. José Lapenta.
ENGLISH
Mycetoma is a chronic granulomatous infectious disease that affects the skin, subcutaneous tissue, and sometimes bone. It is caused by filamentous fungi (eumycetoma) or bacteria (actinomycetoma).
Mycetoma, which was previously believed to be a disease typical of tropical and subtropical regions, has surpassed these areas, with more than 19,000 cases being found in 102 countries from 1876 to 2019, being reported in: México, Sudán, Venezuela, Brazil, the United States, China, Italy, Bulgaria, Germany, the Netherlands, Portugal, Slovenia, Spain, the United Kingdom, Albania, turkey, Australia, India, Pakistan, Egypt, Chad, Ethiopia, Mauritania, Yemen (Asia and African countries).
By 2024, the countries with the highest number of cases are Mexico and Sudan.
CAUSATIVE AGENTS:
In the case of eumycetoma (Fungi) the most common species include Madurella mycetomatis, Pseudallescheria boydii and Acremonium.
Actinomycetoma (Bacteria) is frequently associated with Nocardia brasiliensis, although other species such as Actinomadura and Streptomyces may also be involved.
In Venezuela, the disease predominates in the central-western region of the country, in the states of Lara and Falcón. Cases have also been found in the central regions of Zulia State and Guayana. The most frequently isolated agents in the Falcon State are Actinomadura madurae and Nocardia. brasiliensis.
Other causal agents reported in Venezuela are: Aspergillus ustus, Cyphellophora oxyspora, Exophiala oligosperma, Madurella pseudo mycetomatis, Nocardia farcinica and Nocardia wallacei.
For Eumycetoma in Venezuela, the main etiological agents are: Pyrenochaeta mackinonnii (32%), P. romeroi (24%) and Madurella grisea (20%
CLINICAL MANIFESTATIONS:
The disease is characterized by the formation of tumor-like swellings, sinus tracts and the secretion of grains containing the causative organisms.
Mycetoma is endemic in tropical and subtropical regions, but may appear sporadically in temperate climates.
The foot is the most commonly affected site, (79% of cases) often referred to as "Madura foot", but it can affect any part of the body. The causative organisms usually enter the body through minor skin trauma, such as a prick from thorns (shrubs in tropical and subtropical areas). The classic triad of mycetoma includes a painless subcutaneous mass, fistulas with discharge and the presence of grains.
The disease has been observed in children aged 3 years and in individuals aged 80 years, but predominates in the 2nd decade of life. It is more common in men than in women (2 to 1), and predominates in peasants, affecting mainly the lower limbs, with the foot being the largest organ affected as explained previously.
DIAGNOSIS:
Diagnosis involves clinical evaluation, examination of the grains, microscopy, imaging (e.g., radiography, MRI), and culture. Molecular methods such as PCR and sequencing are increasingly used for rapid and accurate identification, especially in cases with negative cultures.
TREATMENT:
Treatment varies depending on whether the mycetoma is actinomycetoma or eumycetoma:
For eumycetoma, antifungals such as itraconazole or ketoconazole are commonly used. A regimen of 200 to 400 mg daily for a prolonged period (usually six months) is recommended.
Fluconazole, Fosruvoconazole and Amphotericin B have also been used for the treatment of Eumycetoma.
Eumycetoma is more difficult to treat, often requiring prolonged management and not always effective. Surgical intervention, including amputation, may be necessary in severe cases.
Actinomycetoma generally responds best to antibiotics, such as cotrimoxazole (trimethoprim-sulfamethoxazole) and amikacin. As with Eumycetoma, severe cases may require surgery.
Other antibiotics used are: minocycline, amoxicillin, rifampicin, diaminodiphenyl sulfone (DDS) and streptomycin.
PREVENTION:
Preventive measures include wearing protective clothing and footwear, especially in endemic areas. Early diagnosis and treatment are crucial to prevent complications and disability.
Greetings...
Dr. José Lapenta R.
EDITORIAL ESPANOL:
====================
Hola amigos DERMÁGICOS, continuando con el tema de las micosis, hoy una revisión del Mycetoma enfocando el tratamiento del Eumicetoma. Espero que estas 33 referencias bibliográficas nos sean útil para ello.
En el attach 1 lámina ilustrativa del tema: micetoma de la pierna (Acremonium) y actinomicetoma de la region cervico facial (Nocardia).
Saludos,,,
Dr. José Lapenta R.,,,
EDITORIAL ENGLISH:
===================
Hello DERMAGICS friends, continuing with the topic of the mycoses, today a review of the Mycetoma focusing the treatment of the Eumycetoma. I hope these 33 bibliographical references are we useful for it.
In the attach 1 illustrative sheet of the topic: mycetoma of the leg (acremonium) and actinomycetoma of the region facial (neck) (Nocardia).
Greetings,,,
Dr. José Lapenta R.
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DERMAGIC/EXPRESS(43)
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EL MICETOMA / THE MYCETOMA
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1.) Treatment of eumycetoma and actinomycetoma.
2.) Studies on antigens from agents causing black grain eumycetoma.
3.) The antigenic composition and protein profiles of eumycetoma agents.
4.) Treatment of tropical mycoses.
5.) Atypical eumycetoma caused by Phialophora parasitica successfully
treated with itraconazole and flucytosine.
6.) Black grain eumycetoma (Madurella mycetomatis) in the abdominal cavity
of a dog.
7.) Pale grain eumycetomas in Madras.
8.) Improvement of eumycetoma with itraconazole [see comments]
9.) [Black-grain eumycetoma due to Madurella grisea. A report of 2 cases]
10.) Polycytella hominis gen. et sp. nov., a cause of human pale grain
mycetoma.
11.) Fluconazole in the therapy of tropical deep mycoses.
12.) [Mycotic mycetoma (eumycetoma) caused by Madurella mycetomi]
13.) Humoral immune responses to mycetoma organisms: characterization of
specific antibodies by the use of enzyme-linked immunosorbent assay and
immunoblotting.
14.) [Epidemiology of mycetoma in Mexico: study of 2105 cases]
15.) Ultrasonographic imaging of mycetoma.
16.) First report of mycetoma caused by Arthrographis kalrae: successful
treatment with itraconazole.
17.) Mycetoma.
18.) Blood supply and vasculature of mycetoma.
19.) Mycetoma: infection with tumefaction, draining sinuses, and "grains
20.) Mycetoma in the Republic of Niger: clinical features and epidemiology.
21.) Treatment of eumycetoma with ketoconazole.
22.) Eumycetoma caused by Curvularia lunata in a dog.
23.) Diagnostic problems with imported cases of mycetoma in The Netherlands
[see comments]
24.) Ketoconazole in the treatment of fungal infection. Clinical and
laboratory studies.
25.) Fine needle aspiration cytology of mycetoma.
26.) Subcutaneous hyalohyphomycosis caused by Acremonium recifei: case
report.
27.) [Mycetomas in Africa]
28.) Ketoconazole in the treatment of eumycetoma due to Madurella mycetomii.
29.) Mycetoma of the foot caused by Cylindrocarpon destructans.
30.) A clinical trial of itraconazole in the treatment of deep mycoses and
leishmaniasis.
31.) Five-year follow-up of a man with subcutaneous mycetomas caused by
Microsporum audouinii.
32.) A Pan-American 5-year study of fluconazole therapy for deep mycoses in
the immunocompetent host. Pan-American Study Group.
33.) Agents of Mycetoma.
34.) Mycetoma: Report of 3 Cases in Falcón State, Venezuela.
35.) The Global Distribution of Actinomycetoma and Eumycetoma.
36.) Molecular Identification of Unusual Mycetoma Agents Isolated From Patients in Venezuela.
37.) Mycetoma: Reviewing a Neglected Disease.
38.) Autochthonous Cases of Mycetoma in Europe: Report of Two Cases and Review of Literature.
40.) Mycetoma Imaging: The Best Practice.
========================================================================
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1.) Treatment of eumycetoma and actinomycetoma.
========================================================================
Author
Welsh O; Salinas MC; Rodr´iguez MA
Address
Department of Dermatology, Universidad Autonoma de Nuevo Leon, School of
Medicine, Mexico.
Source
Curr Top Med Mycol, 6():47-71 1995
Abstract
Mycetoma is a chronic disease caused by aerobic actinomycetes and eumycetes
which mainly affects the lower extremities. It predominates among farm
workers in tropical, subtropical and adjacent zones. Clinically it is
characterized by a firm swelling with abscesses and fistulae discharging
pus that contains granules or grains of the causal agent. Their color,
size, consistency and histopathology contribute to their identification.
Cultures and metabolic studies determine the disease's etiology. Eumycete
and actinomycete antigens can be used serologically to diagnose and predict
prognosis of the disease. Many different antimicrobials and antifungal
drugs have been used with varying degrees of success.
Trimethoprim-sulfamethoxazole alone or together with
diamino-diphenyl-sulfone is the treatment of choice for actinomycetoma.
Amikacin is used for severe cases, unresponsive to previous treatment, and
for those in danger of dissemination to adjacent organs. Surgery is seldom
used for actinomycetoma. In eumycetoma a combination of medical treatment
and surgery is advised. Small eumycetomas are easily surgically removed.
Ketoconazole at a dosage of 400 mg/day is the medical treatment of choice
for eumycetoma caused by M. mycetomatis. The therapeutic response to
itraconazole varies. Fluconazole has been unsuccessful in the treatment of
eumycetoma but amphotericin B has shown good to poor therapeutic response.
========================================================================
2.) Studies on antigens from agents causing black grain eumycetoma.
========================================================================
Author
Romero H; Mackenzie DW
Address
Universidad de Los Andes, Merida, Venezuela.
Source
J Med Vet Mycol, 27(5):303-11 1989
Abstract
Culture filtrate and cellular antigens prepared from 14 agents which cause
black grain eumycetoma were compared by double diffusion and
immunoelectrophoresis. The fungal agents studied included five isolates of
Madurella grisea, two of Madurella mycetomatis and a single isolate each of
Pyrenochaeta mackinnonii, Pyrenochaeta romeroi, Chaetosphaeronema
(Pseudochaetosphaeronema) larense, Plenodomus avramii, Phoma/Phyllosticta,
Aureobasidium (Exophiala) mansonii and Leptosphaeria senegalensis.
Cross-comparisons between all paired combinations of antigens and rabbit
antisera raised against each antigen, before and after absorption with
heterologous antigens, were expressed as percentage homologies.
Cross-reactivity was marked (up to 90%) within the M. grisea group and
between M. grisea and P. mackinnonii, but not with P. romeroi. The results
suggest that the representatives of the M. grisea group tested were similar
or identical to P. mackinnonii. Little antigenic similarity was observed
between M. grisea and M. mycetomatis. The remaining antigens and antisera
reacted most strongly with their homologous counterparts, except for L.
senegalensis which had antigens in common with M. grisea (0-55% homology)
and P. mackinnonii (70% homology). Analysis of the antigenic patterns
derived from five of six unidentified isolates from patients with black
grain eumycetoma showed marked similarity to M. grisea and P. mackinnonii.
========================================================================
3.) The antigenic composition and protein profiles of eumycetoma agents.
========================================================================
Author
Zaini F; Moore MK; Hathi D; Hay RJ; Noble WC
Address
Department of Medical Mycology, Tehran University of Medical Sciences, Iran.
Source
Mycoses, 34(1-2):19-28 1991 Jan-Feb
Abstract
The protein profiles of different eumycetoma agents were compared by SDS
gel electrophoresis. Dendrograms confirmed the homogeneity of isolates of
Pseudallescheria boydii but amongst Madurella species, particularly
isolates identified as M. grisea, there were substantial differences in
protein composition. However using Western blotting reference isolates of
the different species showed distinct antigen patterns in response to
immune rabbit sera. In particular there was little evidence of cross
reactivity between M. mycetomatis and M. grisea. However this specificity
was not apparent when human sera from patients with different eumycetoma
infections were compared in an ELISA system using the same antigens. It is
possible that the formation of a mycetoma grain may limit a patient's
exposure to antigens which confer specificity, an explanation which may
also account for the variability in antibody responses seen.
========================================================================
4.) Treatment of tropical mycoses.
========================================================================
Author
Restrepo A
Address
Mycology Section, Corporacion para Investigaciones Biologicas, Hospital
Pablo Tobon Uribe, Medellin, Colombia, South America.
Source
J Am Acad Dermatol, 31(3 Pt 2):S91-102 1994 Sep
Abstract
Several subcutaneous and deep-seated mycoses are either observed more
frequently in the tropical areas or are restricted to certain regions
within the tropics. These mycoses include sporotichosis,
chromoblastomycosis, entomophthoromycosis, eumycetoma, lobomycosis, and
paracoccidioidomycosis. In sporotrichosis and paracoccidioidomycosis,
therapy often results in either complete resolution or marked improvement.
For decades sporotrichosis has been treated successfully with potassium
iodide, but recently the triazole compounds, especially itraconazole, have
proved effective and free of major side effects. The usual therapy for
paracoccidioidomycosis is sulfonamides or amphotericin B; the former
requires prolonged treatment, whereas the latter causes a significant
degree of toxicity. Various azole derivatives (ketoconazole, fluconazole,
saperconazole, and itraconazole) allow shorter treatment courses, can be
given orally, and are more effective. Presently, itraconazole is the drug
of choice. Chromoblastomycosis is a difficult condition to treat,
especially if it is caused by Fonsecaea pedrosoi. Several therapeutic
approaches have been used, including heat, surgery, cryotherapy,
thiabendazole, amphotericin B combined with flucytosine, and azole
derivatives, but their success has been modest. A 65% response rate has
been obtained with itraconazole given for periods of 6 to 19 months; in
limited trials, saperconazole appears to be more effective and requires
shorter treatment courses. Only a few patients with eumycetoma respond to
therapy; 70% of patients with Madurella mycetomatis respond to prolonged
treatment with ketoconazole. Griseofulvin has been tried in nonresponders
with partial success. Limited data in patients with Fusarium species
eumycetoma indicate good responses to itraconazole. Eumycetoma caused by
Pseudallescheria boydii or Acremonium species has been refractory to
therapy. Therapy of entomophthoromycosis is also difficult because the
diagnosis is usually established late and not all patients respond to
therapy; this situation applies to infection caused by either Basidiobolus
haptosporus or Conidiobolus coronatus. Although there is no consensus,
African physicians prefer to use potassium iodide or
trimethoprim-sulfamethoxazole. Isolated reports indicate that the azole
derivatives, including the triazoles, may be effective. As for lobomycosis,
all attempts at medical treatment have failed. Surgery is successful only
when the lesion is small and can be fully resected; repeated cryotherapy
appears to be more successful.
========================================================================
5.) Atypical eumycetoma caused by Phialophora parasitica successfully
treated with itraconazole and flucytosine.
========================================================================
Author
Hood SV; Moore CB; Cheesbrough JS; Mene A; Denning DW
Address
Department of Infectious Diseases and Tropical Medicine, North Manchester
General Hospital, UK.
Source
Br J Dermatol, 136(6):953-6 1997 Jun
Abstract
Phialophora species are occasional pathogens causing subcutaneous and
invasive disease. We report the first case of eumycetoma caused by P.
parasitica in an otherwise healthy U.K. resident who visited India. She
failed to respond to surgical excision and itraconazole, 400 mg daily, but
responded to itraconazole, 400 mg daily, and flucytosine, 1 g three times
daily, for 12 months. In vitro susceptibility testing predicted a response.
========================================================================
6.) Black grain eumycetoma (Madurella mycetomatis) in the abdominal cavity
of a dog.
========================================================================
Author
Lambrechts N; Collett MG; Henton M
Address
Department of Surgery, Faculty of Veterinary Science, University of
Pretoria, Republic of South Africa.
Source
J Med Vet Mycol, 29(3):211-4 1991
Abstract
A uterine stump granuloma was surgically removed from a sterilized bitch.
Histopathology and fungal culture revealed Madurella mycetomatis
eumycetoma. Infection may have occurred through a cesarean wound
dehiscence. Long-term fluconazole therapy was instituted but failed to
arrest and eliminate the infection.
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7.) Pale grain eumycetomas in Madras.
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Author
Venugopal PV; Venugopal TV
Address
Institute of Microbiology and Pathology, Madras Medical College, India.
Source
Australas J Dermatol, 36(3):149-51 1995 Aug
Abstract
Biopsy specimens from 211 cases of mycetoma were examined histologically.
Pale grain eumycetoma was found in seven cases. Four of these were studied
mycologically, Acremonium kiliense was isolated from two and Acremonium
falciforme and Pseudallescheria boydii from one case each. The geographic
distribution of these organisms, and their incidence and prevalence are
discussed.
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8.) Improvement of eumycetoma with itraconazole [see comments]
========================================================================
Author
Resnik BI; Burdick AE
Address
Department of Dermatology and Cutaneous Surgery, University of Miami School
of Medicine, Florida, USA.
Source
J Am Acad Dermatol, 33(5 Pt 2):917-9 1995 Nov
Abstract
Treatment of eumycetoma, both medical and surgical, is difficult and often
unsuccessful. We describe a case of maduromycosis, 18 years in duration,
with significant improvement after 6 months of itraconazole therapy.
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9.) [Black-grain eumycetoma due to Madurella grisea. A report of 2 cases]
========================================================================
Author
Machado LA; Rivitti MC; Cuc´e LC; Salebian A; Lacaz C da S; Heins-Vaccari
EM; Belda J´unior W; de Melo NT
Address
Departamento de Dermatologia, Faculdade de Medicina da U.S.P.
Source
Rev Inst Med Trop Sao Paulo, 34(6):569-80 1992 Nov-Dec
Abstract
Two cases of black grains eumycotic mycetoma, occurring on a foot, are
reported. Both proceeded from the state of Bahia (Brazil), and in both the
etiologic agent was Madurella grisea Mackinnon et al., 1949. The grains
structure as well as the micromorphologic characteristics of the fungus in
saprophytic life were studied. It is the author's belief that these
observations correspond to the 7th and 8th cases reported in the Brazilian
medical literature. The authors do consider the following Madurella species
as nomen dubium or nomina confusa: M. ramiroi, M. oswaldoi, M. bovoi, M.
tozeuri, M. mansonii, M. brumpti, M. reynieri, M. americana, M. lackawanna
e M. ikedae and the same for Rubromadurella mycetomi. The only valid
species must be Madurella mycetomatis McGinnis, 1980 (= Madurella mycetomi
Brumpt, 1905) and Madurella grisea Mackinnon et al., 1949. Treatment with
itraconazole in both reported cases, for a 3 month duration, did not
produce any regression of the lesions, the clinical improvement being meager.
========================================================================
10.) Polycytella hominis gen. et sp. nov., a cause of human pale grain
mycetoma.
========================================================================
Author
Campbell CK
Address
Central Public Health Laboratory, London, U.K.
Source
J Med Vet Mycol, 25(5):301-5 1987 Oct
Abstract
A hyphomycete isolated from a pale-grain eumycetoma in an indian male
patient is described as a species of a new form-genus, Polycytella hominis.
The fungus is characterized by elongate multiseptate conidia in which only
the apical compartment becomes thick-walled and retains viable cytoplasm.
The appearance of P. hominis in the host tissues is described and compared
with other pale-grain eumycetomas.
========================================================================
11.) Fluconazole in the therapy of tropical deep mycoses.
========================================================================
Author
Gugnani HC; Ezeanolue BC; Khalil M; Amoah CD; Ajuiu EU; Oyewo EA
Address
University of Nigeria Teaching Hospital, Enugu, Nigeria.
Source
Mycoses, 38(11-12):485-8 1995 Nov-Dec
Abstract
A clinical study was conducted to test the efficacy of fluconazole in the
treatment of tropical deep mycoses. Two out of four patients with
zygomycosis due to Conidiobolus coronatus who were treated with the drug
were completely cured; the other two patients exhibited considerable
improvement but could not be followed up. Two patients with eumycetoma, one
due to an Acremonium sp. and one due to Pseudallescheria boydii, were
treated successfully, whereas another patient with a eumycetoma caused by
an unidentified fungus could not be followed up. A complete cure was
achieved with one patient with African histoplasmosis and one with
candiduria. A case of cerebral phaeohyphomycosis due to Cladosporium sp.
showed some improvement but the patient later developed meningitis and died.
========================================================================
12.) [Mycotic mycetoma (eumycetoma) caused by Madurella mycetomi]
========================================================================
Author
Mittag H; Niedecken HW; Montag H; Bauer R
Source
Hautarzt, 36(5):287-90 1985 May
Abstract
Mycotic mycetoma is a chronic, granulomatous and fistulous tropical disease
caused by hyphomycetes of different families. A case caused by Madurella
mycetomi is presented and the diagnostic and therapeutic possibilities
discussed.
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13.) Humoral immune responses to mycetoma organisms: characterization of
specific antibodies by the use of enzyme-linked immunosorbent assay and
immunoblotting.
========================================================================
Author
Wethered DB; Markey MA; Hay RJ; Mahgoub ES; Gumaa SA
Address
Department of Medical Microbiology, London School of Hygiene and Tropical
Medicine, UK.
Source
Trans R Soc Trop Med Hyg, 82(6):918-23 1988
Abstract
Levels of antibodies were determined by enzyme-linked immunosorbent assay
(ELISA) in 13 patients with eumycetomas due to Madurella mycetomatis
infections. Raised levels of specific IgM were observed in 12 patients,
compared with normal human controls. By contrast, low levels of specific
IgG were detected in some patients. Specific responses to separated protein
antigens were investigated by immunoblotting. Of 10 patients' sera tested,
IgM in 2 recognized up to 7 of the blotted antigens between 45 and 84 kDa.
Gold-labelled protein A (which predominantly binds to IgG) indicated that
sera from 2 patients reacted with at least 6 protein bands with relative
molecular masses between 64 and 95. The demonstration of significant IgM
levels by ELISA, but few antigenic bands in sera from the same patients by
immunoblotting, may point to an antibody response against polysaccharide
fungal antigens in mycetoma patients. The use of the ELISA to detect
antibodies of different classes and the characterization of their antigenic
specificities by immunoblotting may have both diagnostic and prognostic
========================================================================
14.) [Epidemiology of mycetoma in Mexico: study of 2105 cases]
========================================================================
Author
L´opez Mart´inez R; M´endez Tovar LJ; Lavalle P; Welsh O; Sa´ul A; Macotela
Ru´iz E
Address
Departamento de Microbiolog´ia y Parasitolog´ia, Facultad de Medicina,
Universidad Nacional Aut´onoma de M´exico.
Source
Gac Med Mex, 128(4):477-81 1992 Jul-Aug
Abstract
A survey was carried out in Mexico to determine the incidence and
epidemiological characteristics of mycetoma. Data was collected from a
total of 2105 cases of mycetoma throughout a 30 year period (1956-1985),
with an average incidence of 70 cases per year. Results showed a sex
distribution of 76.1% male and 23.9% females. Age distribution indicated a
35% between 16 to 30 and 23% between 31 to 40 year old population. Most
cases occurred in land-workers (60.2%) and in housewives with rural
residence (21.3%). Lesions occurred most frequently in lower limbs (64.1%),
trunk (17.4%) and upper limbs (13.6%). The geographic distribution within
Mexico revealed that the States with the highest incidence were: Jalisco,
Nuevo Le´on, San Luis Potosi, Morelos and Guerrero The predominant
etiologic agents found 97.8% corresponded to actinomycetes, from which
Nocardia brasiliensis (86.6%) and Actinomadura madurae (10.2%) showed the
higher frequency. Eumycetoma (2.2%) was due to Madurella grisea and M.
mycetomatis in most cases.
========================================================================
15.) Ultrasonographic imaging of mycetoma.
========================================================================
Author
Fahal AH; Sheik HE; Homeida MM; Arabi YE; Mahgoub ES
Address
Department of Surgery, Faculty of Medicine, University of Khartown, Sudan.
Source
Br J Surg, 84(8):1120-2 1997 Aug
Abstract
INTRODUCTION: The ultrasonographic appearance of mycetoma is described in
this prospective study. METHODS: One hundred patients with foot swellings
had sonographic evaluation of the swelling and surgical excision within 2
weeks of ultrasonography. The histopathological findings were compared with
the preoperative images. Some of the excised swellings and grains were also
imaged and compared with the in vivo findings. RESULTS: The mycetoma
grains, their capsules and the accompanying inflammatory granulomas have
characteristic ultrasonographic appearances. In eumycetoma lesions, the
grains produce numerous, sharp hyper-reflective echoes and there are single
or multiple thick-walled cavities with no acoustic enhancement. In
actinomycetoma, the findings are similar but the hyper-reflective echoes
are fine, closely aggregated and commonly settle at the bottom of the
cavities. None of the non-mycetoma foot swellings (which included lipoma,
ganglion, foreign body granuloma and others) studied had these features.
CONCLUSION: Ultrasonography is simple, non-invasive, quick, reproducible
and acceptable to patients. Mycetoma has characteristic ultrasonographic
features. Furthermore, ultrasonography delineates the extent of mycetoma
more accurately than clinical examination alone.
========================================================================
16.) First report of mycetoma caused by Arthrographis kalrae: successful
treatment with itraconazole.
========================================================================
Author
Degavre B; Joujoux JM; Dandurand M; Guillot B
Address
Department of Dermatology, University Hospital, N^imes, France.
Source
J Am Acad Dermatol, 37(2 Pt 2):318-20 1997 Aug
Abstract
We report the first case of eumycetoma of the hand caused by Arthrographis
kalrae. Cure was obtained with a 4-month course of itraconazole.
========================================================================
17.) Mycetoma.
========================================================================
Author
Fahal AH; Hassan MA
Address
Department of Surgery, Faculty of Medicine, University of Khartoum, Sudan.
Source
Br J Surg, 79(11):1138-41 1992 Nov
Abstract
Mycetoma is a chronic infective condition of tropical and subtropical
regions. It is commoner in males, especially those in their third or fourth
decade who work on the land. The clinical triad of subcutaneous nodule,
sinuses and discharge usually leads to diagnosis; the disease is commonly
painless. Treatment is by extensive surgical excision of affected areas and
may include limb amputation. Recurrence is common, rates ranging from 20 to
90 per cent. Medical treatment may be used on its own or as an adjunct to
surgery. Although such therapy may cure over half of those with
actinomycetoma (caused by bacteria, mainly aerobic actinomycetes), those
affected by eumycetoma (caused by fungi) have a poorer prognosis and may
require many years of drug therapy.
========================================================================
18.) Blood supply and vasculature of mycetoma.
========================================================================
Author
Fahal AH; el Hag IA; Gadir AF; el Lider AR; el Hassan AM; Baraka OZ;
Mahgoub ES
Address
Department of Surgery, Faculty of Medicine, University of Khartoum, Sudan.
Source
J Med Vet Mycol, 35(2):101-6 1997 Mar-Apr
Abstract
The blood supply to the mycetoma lesion and its vasculature were studied in
patients with various types of mycetoma using histological,
ultrastructural, angiographic and sonographic techniques. The mycetoma
lesion proved to be well vascularized. However, certain vascular
abnormalities were demonstrated. In histological sections, the small
arteries and arterioles showed medial muscular hypertrophy in 83%, intimal
fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed
lumen in 7% of the patients. No vascular occlusion, ischaemic changes or
arteriovenous shunts were observed. These changes were confirmed
ultrastructurally. Angiography of the lesion showed a brisk pathological
circulation which was more evident in eumycetoma. The vascular Doppler
study showed normal blood flow pattern in the affected limb. Regional
intra-arterial chemotherapy for mycetoma is suggested as a possible
treatment modality.
========================================================================
19.) Mycetoma: infection with tumefaction, draining sinuses, and "grains
========================================================================
Author
McElroy JA; de Almeida Prestes C; Su WP
Address
Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905.
Source
Cutis, 49(2):107-10 1992 Feb
Abstract
Mycetoma is a tumorous infection of skin and subcutaneous tissue. It is
caused by either actinomycotic bacteria or eumycotic fungi. The three
cardinal features are tumefaction or the appearance of indolent
inflammatory nodules and secondary fibrosis, formation of sinus tracts and
fistulas that may have the ability to penetrate deep tissue, and the
presence of grains or granules in the affected tissue and discharge.
Although mycetoma is relatively uncommon in the United States, increasing
mobility and changes in demographic characteristics should lead to a
greater awareness of this disease. Characteristic histopathologic findings
and microbiological identification establish the diagnosis. Consequently,
when evaluating what might seem like an ordinary skin or fungal infection,
we must widen our differential diagnosis to include mycetoma. Effective
treatments for actinomycetoma are available, whereas eumycetoma is often
difficult to treat.
========================================================================
20.) Mycetoma in the Republic of Niger: clinical features and epidemiology.
========================================================================
Author
Develoux M; Audoin J; Treguer J; Vetter JM; Warter A; Cenac A
Address
Laboratoire de Parasitologie, Faculte des Sciences de la Sante, Niamey,
Republique du Niger.
Source
Am J Trop Med Hyg, 38(2):386-90 1988 Mar
Abstract
Mycetoma is a common disease in the Republic of Niger. In two hospitals 133
cases were observed. The major site of lesions was the foot.
Actinomycetomata were seen more often than eumycetomata. Streptomyces
somaliensis is prevalent in the north desert zone while Actinomadura
pelletieri is common in the southern part of the country. Madurella
mycetomatis, the usual etiologic agent of eumycetoma, is seen in both
regions. The species incidence and distribution in Niger differs from those
of the west and east African endemic areas.
========================================================================
21.) Treatment of eumycetoma with ketoconazole.
========================================================================
SO - Australas J Dermatol 1993;34(1):27-9
AU - Venugopal PV; Venugopal TV
AD - Institute of Microbiology and Pathology, Madras Medical College, India.
PT - JOURNAL ARTICLE
AB - Ten patients with eumycetoma were treated with oral ketoconazole in
the dosage of 400mg/day for 8 to 24 months. In eight cases the foot was
affected: four were due to Madurella mycetomatis and one each due to M
grisea, Pyrenochaeta romeroi, Acremonium kiliense and A falciorme. One
mycetoma which affected the back and perineum was due to A kiliense, and
one case presented with multiple sebaceous cysts and the scalp and M
mycetomatis was isolated from the lesion. Clinical and laboratory tests
showed excellent tolerance to the drug, with no adverse reactions. Complete
cure was obtained in six patients and two showed good responses. The cured
patients were followed up for a period ranging from three months to two
years without any evidence of recurrence.
========================================================================
22.) Eumycetoma caused by Curvularia lunata in a dog.
========================================================================
SO - Mycopathologia 1991 Nov;116(2):113-8
AU - Elad D; Orgad U; Yakobson B; Perl S; Golomb P; Trainin R; Tsur I;
Shenkler S; Bor A
AD - Kimron Veterinary Institute, Beit-Dagan, Israel.
MT - Animal; Case Report; Male
PT - JOURNAL ARTICLE
AB - Curvularia lunata was cultured from black granules found in
granulomatous tumefactions excised from the subcutis of a three year old
Medium Schnauzer dog. Draining sinuses were present in some of the
tumefactions. Accordingly the diagnosis of eumycotic mycetoma was made.
This diagnosis was confirmed by histopathological examination. During the
four years following the first surgical intervention, several more similar
tumefactions were excised on three different occasions. The dog died of
chronic renal failure at the age of 8 years. There was no bone involvement
or visceral diffusion of the fungus. The granules were examined by scanning
electron microscopy. Immunoglobulins in the dog's serum, assessed by a
qualitative test, proved to be equal to immunoglobulins in the serum of a
control dog. Precipitating antibodies against C. lunata were not found. The
dog was treated for 150 days with itraconazole. In spite of good initial
results, recurrence of the fungal lesions were observed after the
treatment's interruption. Further treatment with itraconazole for 45 days
proved ineffective. No side effects of the drug were observed. This is, to
the best of our knowledge, the first case in which C. lunata is identified
as the causative agent of an animal eumycetoma.
========================================================================
23.) Diagnostic problems with imported cases of mycetoma in The Netherlands
[see comments]
========================================================================
CM - Comment in: Mycoses 1993 Nov-Dec; 36(11-12):341-2
SO - Mycoses 1993 Mar-Apr;36(3-4):81-7
AU - de Hoog GS; Buiting A; Tan CS; Stroebel AB; Ketterings C; de Boer EJ;
Naafs B; Brimicombe R; Nohlmans-Paulssen MK; Fabius GT; et al
AD - Centraalbureau voor Schimmelcultures, Baarn, The Netherlands.
PT - JOURNAL ARTICLE
AB - Eight cases of imported mycetomata in The Netherlands are reviewed.
Seven of these were cultured; only one isolate, Actinomadura madurae,
belonged to a species commonly known as an agent of mycetoma. The remaining
strains either belonged to very rare species, such as Phialophora
cyanescens, or could not be identified at all. The list of possible agents
of mycetoma apparently needs to be expanded. In addition, the concept of
endemic occurrence of aetiological agents of eumycetoma needs revision.
Divergent saprophytes may be involved which are able to survive in human
tissue.
========================================================================
24.) Ketoconazole in the treatment of fungal infection. Clinical and
laboratory studies.
========================================================================
SO - Am J Med 1983 Jan 24;74(1B):16-9
AU - Hay RJ
MT - Comparative Study; Female; Human; Male
PT - JOURNAL ARTICLE
AB - Ketoconazole is an effective treatment for chronic superficial
candidiasis as well as chronic dermatophytosis. In the latter group of
infections the best results were obtained in patients with tinea corporis
who were not responsive to griseofulvin. It is possible to maintain some
patients with chronic mucocutaneous candidiasis in remission without using
prophylactic ketoconazole, although relapses may occur. However, the
responses of patients with Hendersonula and Scytalidium infections as well
as those with subcutaneous mycoses, such as eumycetoma, were disappointing.
Patients who have an inadequate response to ketoconazole may also have
subnormal serum levels of the drug and the value of such estimations in
routine management needs further evaluation.
========================================================================
25.) Fine needle aspiration cytology of mycetoma.
========================================================================
AU: EL-Hag-IA; Fahal-AH; Gasim-ET
AD: Department of Pathology, Faculty of Medicine, University of Khartoum,
Sudan.
SO: Acta-Cytol. 1996 May-Jun; 40(3): 461-4
ISSN: 0001-5547
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE: To describe fine needle aspiration cytology of mycetoma and
determine its usefulness in diagnosis. STUDY DESIGN: The study group
consisted of 14 patients with different types of mycetoma lesions, which
were aspirated. Smears were reviewed without knowing the type of mycetoma,
and the findings were compared with those observed in histologic sections.
RESULTS: In mycetoma, the causative organisms have a distinct appearance on
cytologic smears. They are surrounded and infiltrated by neutrophils in a
background of polymorphous, inflammatory cells consisting of neutrophils,
histiocytes, lymphocytes, plasma cells, macrophages and foreign body giant
cells. This allows differentiation from artifacts and inflammatory lesions
caused by other bacteria and fungi. The distinction between eumycetoma and
actinomycetoma in fine needle aspiration cytology was found to be as
accurate as is histopathology when the grains were present. CONCLUSION:
These results demonstrate that mycetoma can be accurately diagnosed by fine
needle aspiration cytology. The technique is simple, inexpensive, rapid and
sensitive. It can be used in the routine diagnosis of mycetoma, in
epidemiologic surveys and in material collection.
========================================================================
26.) Subcutaneous hyalohyphomycosis caused by Acremonium recifei: case
report.
========================================================================
AU: Zaitz-C; Porto-E; Heins-Vaccari-EM; Sadahiro-A; Ruiz-LR; Muller-H;
Lacaz-C-da-S
AD: Department of Medicine, Faculty of Medical Sciences, Santa Casa of Sao
Paulo, Brazil.
SO: Rev-Inst-Med-Trop-Sao-Paulo. 1995 May-Jun; 37(3): 267-70
ISSN: 0036-4665
PY: 1995
LA: ENGLISH
CP: BRAZIL
AB: We present a case of subcutaneous hyalohyphomycosis due to Acremonium
recifei, a species whose habitat is probably the soil, first identified in
1934 by Area Leao and Lobo in a case of podal eumycetoma with
white-yellowish grains and initially named Cephalosporium recifei. A white
immunocompetent female patient from the state of Bahia, Brazil, with a
history of traumatic injury to the right hand is reported. The lesions was
painless, with edema, inflammation and the presence of fistulae.
Seropurulent secretion with the absence of grains was present.
Histopathological examination of material stained with hematoxylin-eosin
showed hyaline septate hyphae. A culture was positive for Acremonium
recifei. Treatment with itraconazole, 200 mg/day, for two months led to a
favorable course and cure of the process. We report for the first time in
the literature a case of subcutaneous hyalohyphomycosis due to Acremonium
recifei in a immunocompetent woman. Treatment with itraconazole 200 mg/day,
for two months, resulted in cure.
========================================================================
27.) [Mycetomas in Africa]
========================================================================
TO: Les mycetomes en Afrique.
AU: Develoux-M; Ndiaye-B; Dieng-MT
AD: Travail de la clinique dermatologique, Hopital A. Le Dantec, Dakar,
Senegal.
SO: Sante. 1995 Jul-Aug; 5(4): 211-7
ISSN: 1157-5999
PY: 1995
LA: FRENCH; NON-ENGLISH
CP: FRANCE
AB: Mycetoma is the pathological process in which exogenous fungal or
actinomycotic etiological agents generate grains. These agents belong to
two groups: fungi and aerobic actinomycetes. Eumycetoma (caused by fungi)
and actinomycetoma (caused by actinomycetes) must be distinguished as their
treatments are different. These causative agents are introduced by traumas.
Mycetomas are frequent in the northern tropical zones of America in Mexico
and Venezuela, Africa in Senegal, Mauritania and Sudan and Asia in India,
but can also be observed beyond these areas. In Africa, a high endemicity
has been noted in a Sahelian band spanning from Senegal and Mauritania in
the west to Somalia and the Republic of Djibouti in the east where there
are long dry seasons and short rainy seasons. In this zone, M. mycetomatis
(fungi) and S. somaliensis (actinomycetes) are predominant. A. pelletieri
is common only in West Africa. Rainfall influences the distribution of
these agents. S. somaliensis is more often found in desert areas, and A.
pelletieri in more rainy areas. Mycetoma is more frequent in males and
affects the age group between the second and fourth decades. Most of the
patients are outdoor workers. In Africa, the foot is the most frequent
localisation of the disease followed by the leg. Mycetoma is characterized
by tumefaction, subcutaneous nodules and in most cases discharging sinuses
that drain exudate containing grains. It gradually invades the tissues and
bones causing a functional disability. Bone involvement depends on the
duration of the disease, the site of the lesion and the causative agent.
Invasion of lymph nodes is observed in rare cases, usually with
actinomycetes.(ABSTRACT TRUNCATED AT 250 WORDS)
========================================================================
28.) Ketoconazole in the treatment of eumycetoma due to Madurella mycetomii.
========================================================================
Author(s) Mahgoub ES; Gumaa SA
Source Trans R Soc Trop Med Hyg 1984;78:376 - 9.
Abstract Eumycetoma is, at present, treated only by surgery which is
amputation at times and mutilating excision at others. Surgical treatment
is often followed by local, or rarely distant recurrence to regional lymph
nodes and surrounding tissue. The results of the clinical trial with
ketoconazole reported in this paper show that five of 13 patients were
completely cured and four improved. It is worth noting that the daily dose
for those cured was 400 or 300 mg while those who improved were on only 200
mg/day.
========================================================================
29.) Mycetoma of the foot caused by Cylindrocarpon destructans.
========================================================================
Author(s) Zoutman DE; Sigler L
Address Department of Medical Microbiology and Infectious Diseases,
University of Alberta, Edmonton, Canada.
Source J Clin Microbiol 1991;29:1855 - 9.
Abstract
A 39-year-old male, originally from Antigua, West Indies, presented with a
12-year history of swelling of the left foot. A pathogen could not be
recovered in cultures of three surgical biopsy specimens. During follow-up,
pus and grains were expressed from a draining sinus tract and
Cylindrocarpon destructans grew in pure culture. Retrospective examination
of histologic sections of tissue removed during the third biopsy
demonstrated a grain characteristic of eumycotic mycetoma. Although the
fungus was susceptible to amphotericin B and ketoconazole in vitro, the
patient refused treatment, and the clinical course over almost 19 years has
been one of slow but progressive bone destruction. The fungus was
identified by its microconidial morphology, the presence of chlamydospores,
and an intense brown diffusible pigment. It was compared with another
poorly known agent of white grain mycetoma, Phialophora cyanescens,
characterized by phialidic conidia, chlamydospores in aggregations, and an
intense diffusing pigment. The new combination Cylindrocarpon cyanescens
(de Vries et al.) Sigler comb. nov. is proposed.
========================================================================
30.) A clinical trial of itraconazole in the treatment of deep mycoses and
leishmaniasis.
========================================================================
Author(s) Borelli D
Source Rev Infect Dis 1987;9(Suppl 1):S57 - 63.
Abstract Itraconazole was administered orally to two patients with
sporotrichosis, 10 patients with paracoccidioidomycosis, three with
mycetomas (due to Madurella grisea, Streptomyces madurae, and
Pseudochaetosphaeronema larense, respectively), nine with chromomycosis due
to Cladosporium carrionii, five with chromomycosis due to Fonsecaea
pedrosoi and five with leishmaniasis (including one with the nodular
disseminated form). The clinical and laboratory tests showed excellent
tolerance to the drug with a total absence of adverse reactions.
Satisfactory results were achieved against paracoccidioidomycosis,
sporotrichosis, and chromomycosis due to C. carrionii (apparent cure was
achieved in a short time). Encouraging improvement was noted in the
treatment of mycetoma due to M. grisea. Among the five cases of
leishmaniasis, a complete clearing was achieved in one and an encouraging
improvement in two, including the one with the nodular disseminated form.
Two patients with F. pedrosoi infection were apparently cured after the
addition of thermotherapy and flucytosine, respectively, to the treatment
regimen.
========================================================================
31.) Five-year follow-up of a man with subcutaneous mycetomas caused by
Microsporum audouinii.
========================================================================
Author(s) West BC
Source Am J Clin Pathol 1982;77:767.
Abstract
A black man with subcutaneous mycetomas caused by Microsporum audouinii was
treated by a combination of griseofulvin, 18.5 g of amphotericin B,
excisional surgery, and later, ketoconazole, resulting in a satisfactory
arrest or cure of the clinical illness. Complications of therapy included
residual impaired renal function and a change in hair color from black to a
rust brown color. The continued use of the term mycetoma to describe such
lesions is justified.
========================================================================
32.) A Pan-American 5-year study of fluconazole therapy for deep mycoses in
the immunocompetent host. Pan-American Study Group.
========================================================================
Author(s) Diaz M; Negroni R; Montero-Gei F; Castro LG; Sampaio SA; Borelli
D; Restrepo A; Franco L; Bran JL; Arathoon EG; et al
Address Universidad Autonoma de Nuevo Leon, Hospital Universitario,
Monterrey, Mexico.
Source Clin Infect Dis 1992;14(Suppl):568 - 76.
Abstract
Eighty-eight immunocompetent patients with deep mycoses from eight
countries were evaluated with the same protocol for efficacy of fluconazole
monotherapy. Entry doses were raised from 100 to 400 mg as safety was shown
in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44
months were studied. Results were very similar in different countries.
Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19
with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight
with histoplasmosis demonstrated objective responses to therapy, as did one
patient each with zygomycosis and alternariosis. For these patients,
relapses have been unusual thus far. In contrast, one patient with
chromoblastomycosis responded but relapsed, and six did not respond; one
patient with mycetoma responded but relapsed, and two did not respond. The
drug was well tolerated by patients, including six who received intravenous
therapy. In vitro susceptibility tests suggested that clinical response was
correlated with susceptibility but that resistance did not preclude
clinical response. Fluconazole therapy appears efficacious for several deep
mycoses; dosages of greater than 200 mg daily may be needed for some
diseases. The further evaluation of fluconazole for these entities is
warranted.
========================================================================
33.) Agents of Mycetoma
========================================================================
Source: Mandell, Douglas and Bennett's
Principles and Practice of Infectious Diseases
Fourth Edition
Dr. El Sheikh Mahgoub
Mycetoma (Madura foot) is a local, chronic, slowly progressive, often
painless destructive infection of the skin, subcutaneous tissues, fascia,
bone, and muscle. After implantation of the organism, which is often
associated with soil or plant debris, the infection, usually on a foot or
hand or any site that is subject to trauma, produces a localized swelling
containing suppurative granulomas and multiple sinus tracts that extrude
grains (granules) of various colors. 1,2 The grains are actual colonies of
the causal organism.
Etiology
--------
Two different types of mycetoma are recognized. Mycetoma caused by true
fungi (Eumycetes) is referred to as eumycetoma. The causal fungi described
so far include Pseudallescheria boydii, Madurella mycetomatis, Madurella
grisea, Phialophora jeanselmei, Pyrenochaeta romeroi, Leptosphaeria
senegaliensis, Curvalaria lunata, Neotestudina rosatii, Aspergillus
nidulans or flavus, and species of Fusarium, Cylindrocarpon, 3 and
Acremonium. Actinomycetoma refers to infection caused by aerobic
actinomycetes including Actinomadura madurae, Actinomadura pelletieri,
Streptomyces somaliensis, Nocardia brasiliensis, Nocardia asteroides, and
Nocardia otitidiscaviarum (N. caviae). 4 Whether N. transvalensis is a
separate species remains an open question but mycetoma has been attributed
to this organism. 5 Several species of dermatophytes also cause a
mycetomalike infection of the scalp and neck, 6,7 but dermatophytes are not
considered agents of mycetoma because they do not invade bone.
Epidemiology
------------
In 1842, Gill described the disease for the first time in India in a
dispensary in Madura District, 8 hence the derivation of Madura foot,
maduromycetoma, Madurella, and Actinomadura madurae. Both Bidie in 1862 and
Carter in 1874 9,10 quite independently from one another have given a full
account of the disease and its incidence in India. Today, mycetoma is found
worldwide between the Tropics of Cancer and Capricorn. The infection is
seen most often in India, Mexico, Niger, Saudi Arabia, Senegal, Somalia,
Sudan, Venezuela, Yemen, and Zaire but is not limited to these areas.
Mycetoma in temperate zones has been reported from time to time.
The most frequent cause of the disease in the United States is
Pseudallescheria boydii, which has been isolated frequently from soil in
the United States and Canada. 11 Madurella mycetomatis and S. somaliensis
predominate in tropical areas of Africa and India, and Nocardia
brasiliensis and A. madurae are the most common cause of mycetoma in Mexico
and Central and South America. 12 Nocardia asteroides is reported to
predominate in Japan.
Pathogenesis and Pathologic Findings
-------------------------------------
Saprophytic soil fungi enter the tissues of the bare foot or hand after
local trauma most commonly by a thorn prick, wood splinter, or stone cut.
The chest wall and back are infected by sacks contaminated with soil
carried over the shoulders. The carrying of wood bundles on the head and
shoulders leads to head and neck mycetoma.
The infection begins in the skin and subcutaneous tissues. Mycetoma tends
to follow fascial planes in its proximal, lateral, and deep spread as it
progressively involves and destroys connective tissue and bone.
In histologic sections stained with hematoxylin and eosin (H&E), involved
tissue reveals a suppurative granuloma. Grains are seen embedded in an
abscess composed of neutrophils accompanied by an outer epithelioid cell,
plasma cell, and multinucleated giant cell reaction intermingled with areas
of fibrosis. Within these suppurative foci the grains are surrounded by an
amorphous eosinophilic, homogeneous hyalinelike material termed the
Splendore-Hoeppli phenomenon. Ultrastructural studies have revealed that
this part of the grain matrix is host derived. 13
The appearance of various grains in sections is so characteristic that it
allows specific diagnosis of the causative organism. 14 Eumycetic hyphae
within the grain are easy to see at ´400 magnification, whereas those of
actinomycetes are difficult to visualize even at ´800.
In electron micrographs concentric rings of cell wall thickening and coarse
cell wall fibrils around cells are seen within eumycetic grains.
The involved area is characterized by tumefaction, multiple sinus
formation, and fistulous tracts that communicate with each other, with deep
abscesses, and with ulcerated areas of the skin. The progressive
proliferation of granulation and scar tissue leads to enlargement and
disfigurement of the affected part.
Clinical Manifestations
-----------------------
Mycetoma is seen most frequently in men between the ages of 20 and 40. A
true male-to-female ratio is 5:1. It occurs most often in farmers and other
laborers in rural areas, bedouins, and nomads, who are frequently exposed
to penetrating wounds by thorns and splinters. The most common site of
infection is the foot, particularly on the dorsum of the fore part. A
painless massively swollen indurated foot riddled with sinuses is the late
presentation (Fig. 1). Constitutional complaints are rare, and pyrexia
implies secondary bacterial infection. Extrapedal cases appear on other
parts of the body in contact with soil during work, sitting, or lying; thus
the hand (Fig. 2), leg, torso, arm, head, thigh (Fig. 3), and buttocks may
also be infected. When the scalp is involved, it usually starts in the back
of the head and neck or the frontal part.
The earliest manifestation is a small painless papule or nodule on the sole
or dorsum of the foot that progressively increases in size. Such
development is usually quicker in actinomycetoma than eumycetoma. The skin
lesions swell and rupture with sinus tract formation. As the infection
spreads, similar lesions appear on adjacent parts. Old sinuses heal and
close up, but new ones open at other sites. Thus, an old mycetoma is
characterized by healed scars in addition to sinuses. Months or years
later, destruction of deeper tissues, including bone, is manifested as
generalized swelling that remains painless except in about 15 percent of
patients who report to the hospital primarily because of pain.
The course is progressive as local tissue undergoes a recurring cycle of
swelling, suppuration, and scarring. Ultimately, an infected site becomes a
swollen deformed mass of destroyed tissue with many fistulae through which
grains are discharged. The infection never spreads hematogenously, but
regional lymphadenopathy may occur. 15 Involved tissue may become
secondarily infected by bacteria.
In the bone, the cortex is invaded, and masses of grains gradually replace
osseous tissue and marrow. Radiographs reveal multiple osteolytic lesions
called cavities (Fig. 4) and periosteal new bone formation. Osteoporosis
due to pressure by surrounding swelling and disease atrophy is also seen at
times. Joints are sometimes stiff because of chronic periarticular fibrosis.
Mycetomas of the skull show diffuse thickening of bones due to dense bone
formation and a loss of the trabecular pattern, but in a few areas there
may be small osteolytic areas as well. 16 Pure osteolytic changes are not
seen.
Diagnosis
---------
The triad of signs, indurated swelling, multiple sinus tracts draining
grain-filled pus, and the usual localization on a foot characterize a
well-developed mycetoma. 17 Characteristic grains in draining sinuses are
0.2–3.0 mm in diameter and may be black, white, yellow, pink, or red
depending on the causal organism. Grains may be difficult to locate in
histopathologic sections and require multiple cuts through the
paraffin-embedded tissue. H&E stain is adequate to detect the grains (Fig.
5). Tissue gram staining will detect fine branching hyphae within the
actinomycetoma grain, and Gomori methenamine silver or periodic acid–Schiff
(PAS), particularly in the case of pale grains, will detect the larger
hyphae of eumycetoma. Species of the agent can often be guessed by the
color, size, compaction, and hematoxylin-staining character of the grain. 1
A more exact species diagnosis is dependent on culture of the grain and
isolation of the organism. The grain obtained for culture must be as free
as possible from bacterial and fungal contamination. A wedge-shaped,
deep-seated biopsy provides a good specimen for both histologic and
cultural diagnosis. Before being inoculated onto culture media, the grains
should be rinsed quickly in 70% alcohol and washed several times in sterile
saline. Biopsy specimens are preferred over grains discharged through
sinuses because these grains may be contaminated with surface organisms or
may already be dead. For primary isolation actinomycetoma grains are grown
on Löwenstein-Jensen medium and fungal grains on blood agar. Sabouraud agar
(2% glucose peptone agar) without antibacterial antibiotics is a
satisfactory for subcultures.
Serologic diagnosis is at present routinely used in a few centers. Using
cell extract antigens, antibodies are determined by means of
immunodiffusion (ID) or counterimmunoelectrophoresis (CIE) for both
serologic diagnosis and follow-up during medical treatment. 18
More recent specific characterization of antibodies was done by
enzyme-linked immunoassay (ELISA) and Western blotting. 19 Also using the
Western blot, three immunodominant antigens from extracts of N.
brasiliensis were found to react with sera from patients having mycetoma
due to this organism. 20
Differential Diagnosis
----------------------
In endemic areas,a painless, firm, subcutaneous swelling should be regarded
as a mycetoma until proved otherwise even in the absence of sinuses. Once
mycetoma has invaded bone, the entity is readily confused with chronic
bacterial osteomyelitis. Botryomycosis is a chronic bacterial infection
that presents as an indurated fibrotic subcutaneous mass and draining
sinuses resembling a mycetoma; grains (colonies of bacteria) are found in
the purulent exudate and in tissue sections. Although botryomycosis is most
commonly a disease of the skin and subcutaneous tissues, unlike mycetoma,it
may also involve viscera. The etiologic agents of botryomycosis include a
number of gram-positive cocci (staphylococci, streptococci) and
gram-negative bacilli (Escherichia coli, Pseudomonas, Proteus species). In
the absence of sinuses, mycetoma should be differentiated from benign or
malignant tumors, a cold abscess, or a thorn granuloma. 21
Treatment and Prognosis
-----------------------
Through health education, patients are encouraged to report early to
hospitals. Surgical treatment, which is unfortunately still preferred by
some doctors, will either lead to immediate recurrence as a result of
incomplete excision or a mutilating result for a relatively painless
disease. Mycetoma at all stages could be amenable to medical treatment
alone or in combination with limited surgery. In a medicosurgical approach,
only bulk reduction surgery is performed, but amputation or disarticulation
should be avoided. The success of treatment depends not only on the
differentiation between actinomycetoma and eumycetoma but also on a
definitive identification of the causal organism.
In all cases of actinomycetoma, a combination of two drugs is used. 22 One
of these is always streptomycin sulfate in a dose of 14 mg/kg daily for the
first month and on alternate days thereafter. In patients with A. madurae,
dapsone is given orally at 1.5 mg/kg in the morning and evening. Similarly,
S. somaliensis mycetoma is treated by dapsone first, but if no response
appears after 1 month, treatment is changed to
trimethoprim-sulfamethoxazole tablets at 23 mg/kg/day of sulfamethoxazole
and 4.6 mg/kg/day of trimethoprim (in two divided doses). Actinomadura
pelletierii mycetoma responds better to streptomycin and
trimethoprim-sulfamethoxazole, which was also our experience with N.
brasiliensis in Sudan. However, such mycetoma due to Nocardia in the
Americas is treated with trimethoprim-sulfamethoxazole and dapsone 23 or
trimethoprim-sulfamethoxazole and amikacin. 24 Because amikacin could have
deleterious side effects in patients with renal disease and because of its
high cost, it is kept as a second-line treatment when first-line treatment
fails. Treatment is given in cycles of simultaneous administration of two
divided doses of amikacin (15 mg/kg/day) for 3 weeks and
trimethoprim-sulfamethoxazole (7–35 mg/kg/day) for 5 weeks. The cycle is
repeated again and rarely for a third time as the need arises. 25
Eumycetoma due to M. mycetomatis also responds very well to this
medicosurgical approach using ketoconazole, 14,25-28 200 mg twice daily.
Rare cases of mycetoma due to A. nidulaus, A. flavus, or Fusarium have
responded well to itraconazole in a dose of 100 mg twice daily.
Intravenous liposomal amphotericin B has been tried in patients with
mycetoma due to M. grisea and Fusarium spp. in an average total dose of 3.5
g with a maximum daily dose of 3 mg/kg body weight. Only temporary
remission was obtained. 25
In all cases of medical management, treatment is given for at least 10
months (Fig. 6). Although side effects are few, patients are regularly
followed up by assessing hematologic, kidney, or liver functions, depending
on the drug used.
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DATA-MÉDICOS/DERMAGIC-EXPRESS No (43) 04/03/99 DR. JOSE LAPENTA R.
======================================================================
Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024
Producido por Dr. José Lapenta R. Dermatólogo
Venezuela
1.998-2.024
Tlf: 0414-2976087 - 04127766810
