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****** DATA-MÉDICOS **********
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EL MICETOMA 
THE MYCETOMA 
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****** DERMAGIC-EXPRESS No.40 ******* 
****** 04 MARZO DE 1.999 ********* 
04 MARCH 1.999
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EDITORIAL ESPAÑOL:
=====================
Hola amigos DERMAGICOS, continuando con el tema de las micosis, hoy una revisión del Micetoma enfocando el tratamiento del Eumicetoma.

Espero que estas 33 referencias bibliográficas nos sean util para ello. 

En el attach 1 lamina ilustrativa del tema: Micetoma de la pierna (Acremonium) y Actinomicetoma de la región cérvico facial (Nocardia). 


Saludos a TODOS,,, 

Dr. José Lapenta R.,,,

EDITORIAL  ENGLISH:
=====================
Hello DERMAGICS friends, continuing with the topic of the mycoses, today a revision 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 facial region  (neck) (Nocardia). 

Greetings to ALL, 

Dr. Jose Lapenta R.,,,


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DERMAGIC/EXPRESS (40)
================================================================
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.
================================================================ ================================================================
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. 

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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. 

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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. 

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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. 
========================================================================
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. 

========================================================================
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. 

========================================================================
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

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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 Mexico. 
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. 

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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. 

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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. 

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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. 

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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. 

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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. 

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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.

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26.) Subcutaneous hyalohyphomycosis caused by Acremonium recifei: case report.
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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.

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27.) [Mycetomas in Africa]
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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)

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28.) Ketoconazole in the treatment of eumycetoma due to Madurella mycetomii.
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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.

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29.) Mycetoma of the foot caused by Cylindrocarpon destructans.
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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.

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30.) A clinical trial of itraconazole in the treatment of deep mycoses and leishmaniasis.
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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.

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31.) Five-year follow-up of a man with subcutaneous mycetomas caused by Microsporum audouinii.
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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.

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32.) A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan-American Study Group.
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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.

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33.) Agents of Mycetoma
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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
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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-MEDICOS/DERMAGIC-EXPRESS No (40) 04/03/99 DR. JOSE LAPENTA R. 
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