Journal of General - Procedural Dermatology & Venereology Journal of General - Procedural Dermatology & Venereology Indonesia
Indonesia
Volume 1
Number 2 Vol. 1, No. 2 (June 2016) Article 1
6-30-2016
Subcutaneous mycosis at the Department of Dermatology and Subcutaneous mycosis at the Department of Dermatology and Venereology dr. Cipto Mangunkusumo National Hospital, Jakarta, Venereology dr. Cipto Mangunkusumo National Hospital, Jakarta, 1989-2013
1989-2013
Sammy Yahya
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital, Jakarta
Sandra Widaty
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital, Jakarta
Eliza Miranda
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital, Jakarta
Kusmarinah Bramono
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital, Jakarta
Artini Wijayanti Islami
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital, Jakarta
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Recommended Citation Recommended Citation
Yahya, Sammy; Widaty, Sandra; Miranda, Eliza; Bramono, Kusmarinah; and Islami, Artini Wijayanti (2016)
"Subcutaneous mycosis at the Department of Dermatology and Venereology dr. Cipto Mangunkusumo National Hospital, Jakarta, 1989-2013," Journal of General - Procedural Dermatology & Venereology Indonesia: Vol. 1: No. 2, Article 1.
DOI: 10.19100/jdvi.v1i2.30
Available at: https://scholarhub.ui.ac.id/jdvi/vol1/iss2/1
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Original Articles
Subcutaneous mycosis at the Department of Dermatology and Venereology dr. Cipto Mangunkusumo National Hospital,
Jakarta, 1989-2013
Sammy Yahya, Sandra Widaty, Eliza Miranda, Kusmarinah Bramono, Artini Wijayanti Islami
Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo National Hospital, Jakarta
email: [email protected]
Abstract
Introduction: Subcutaneous mycosis (SM) is a fungal infection involving dermis and subcutaneous tissue, which can disseminate slowly through systemic blood or lymphatic circulation. The subacute or chronic infection usually found in workers of rural tropical and subtropical area. SM occurs due to trauma along with other predisposing factors such as sex, genetic and occupation.
Aim: To identify the types of SM, its clinical findings, laboratory work-up and the treatment at the Dermatomycology Division, Department of Dermatology and Venereology dr. Cipto Mangunkusumo National Hospital between the year 1989 and 2013.
Method: This retrospective study collected data from medical records and case reports of patients with SM who came at Department of Dermatology and Venereology dr. Cipto Mangunkusumo National Hospital (1989-2013).
Results: We found 16 cases of SM, i.e. subcutaneous mucormycosis (5 cases), eumycetoma (4 cases), actinomycetoma (4 cases) and chromoblastomycosis (3 cases). There was a greater number of male than female patients ratio (3:1) and mostly were in the age group of 25-44 years. The direct microscopic examination did not reveal any fungal element, except for black spora in chromoblastomycosis (1 case).
The culture revealed Basidiobolus ranarum in subcutaneous mucormycosis (5 cases), Nocardia transvalensis in actinomycetoma (1 case) and Phialophora sp. in 1 case of chromoblastomycosis. On histopathological examination, we found fine granules of actinomycetoma, sulphuric granules of actinomycetoma, coenocytic hyphae of subcutaneous mucormycosis, eosinophilic granule in 1 case of mycetoma and hyphae with black spore in chromoblastomycosis.
Conclusion: SM is still a rare disease, comprehensive management of SM needs supporting laboratory work-up, particularly the histopathological examination.
Keywords: Mycosis, subcutaneous, culture, histological
Abstrak
Pendahuluan: Mikosis subkutan (MS) merupakan infeksi jamur yang melibatkan dermis dan jaringan subkutan, dapat berdiseminasi lambat secara hematologik atau limfatik. Kelainan bersifat subakut maupun kronik, umumnya ditemukan pada pekerja didaerah pedesaan beriklim tropis dan subtropis. Mikosis subkutan terjadi akibat trauma yang memudahkan inokulasi mikroorganisme penyebab kedalam kulit.
Faktor predisposisi lain adalah jenis kelamin, genetik, dan pekerjaan.
Tujuan: Mengetahui jenis MS, temuan klinis, pemeriksaan penunjang, serta terapinya di Divisi Dermatomikologi Departemen Ilmu Kesehatan Kulit dan Kelamin RS. Dr. Cipto Mangunkusumo (IKKK RSCM) periode1989-2013.
Metode: Data dikumpulkan secara retrospektif dari rekam medis dan laporan kasus pasien MS yang datang berobat di Departemen IKKK RSCM (1989-2013).
Hasil: Didapatkan 16 kasus MS yaitu mukormikosis subkutan (5 kasus), eumisetoma (4 kasus),
aktinomisetoma (4 kasus), dan kromoblastomikosis (3 kasus). Pasien pria lebih banyak daripada wanita (3:1) dengan kelompok usia terbanyak pada rentang 25-44 tahun. Umumnya pemeriksaan mikroskopik langsung tidak ditemukan elemen jamur, kecuali spora hitam pada kromoblastomikosis (1 kasus). Pada pemeriksaan kultur ditemukan Basidiobolus ranarum pada mukormikosis subkutan (5 kasus), Nocardia transvalensis pada aktinomisetoma (1 kasus), serta Phialophora sp. pada 1 kasus kromoblastomikosis.
Pada pemeriksaan histopatologik ditemukan granul halus pada 1 kasus aktinomisetoma, granul sulfur pada 2 kasus aktinomisetoma, hifa coenocytic pada 1 kasus mukormikosis subkutan, granul eosinofilik pada 1 kasus misetoma, serta hifa dan spora hitam pada kasus kromoblastomikosis.
Kesimpulan: MS masih mrtupoakan penyakit yang jarang ditemukan. Tatalaksana komprehensif MS memerlukan pemeriksaan penunjang yang mendukung terutama didapatkan dari pemeriksaan histopatologik.
Katakunci: Mikosis, subkutan, kultur, histologi
Introduction
Subcutaneous mycosis (SM) is a fungal infection, which involves dermis and subcutaneous tissue thorough fungal inoculation due to injury penetrating into the skin, and it rarely causes dissemination in immunocompetent host. Subcutaneous mycosis is usually sporadic and commonly found in tropical and subtropical area.1,2 Various contributing factors of SM are male, genetic factor and type of occupation.4 There were 29 cases of SM in 5 teaching hospitals in South Sumatera, West Java and East Java.5 While the number of SM case in 10 teaching hospitals in Indonesia between 2007 and 2012 was 61 cases.5 A report on SM profile in Sanglah Central National Hospital in Denpasar shows that there were 11 cases between 2005 and 2009. The types of SM reported in Indonesia are actinomycetoma, eumycetoma,
subcutaneous mucormycosis,
chromoblastomycosis, sporotrichosis,
lobomycosis, subcutaneous
phaeohyphomycosis and protothecosis.6 Mycetoma is a type of SM caused by bacteria (actinomycetoma) or fungi (eumycetoma). The most common cause of eumycetoma is Madurella mycetomatis. Clinical diagnosis of mycetoma is made based on clinical morphology, i.e. subcutaneous nodes, sinus and granules. The culture may reveal granules that support the diagnosis.1,2,7 While the histopathological examination may reveal granules in an abscess. The management of eumycetoma is difficult and frequently needs a combination of pharmacological and surgical treatment. Itraconazole and terbinafine are considered as alternative treatments for eumycetoma. The treatment of choice for
actinomycetoma is a combination of dapsone with streptomycin or amikacin.1,7
Subcutaneous mucormycosis is a mycosis characterized by hard swelling of subcutaneous tissue.1,8 It was first discovered by Lie Kian Joe et al in 1956 in Indonesia.9 Aguani et al. found 18 cases of subcutaneous mucomycosis in East Java between 1958 and 1987.10 It may be caused by Basidiobolus ranarum (B. ranarum), which commonly occurs in children. Another type is caused by Conidiobolus coronatus, which is found in adults. The lesion is painless and it may be itchy.1,8 On histopathological examination, large hyphae surrounded by eosinophilic mass can be found, which is known as the Splendore- Hoeppli phenomenon. Treatment using ketoconazole, itraconazole, or potassium iodide provides complete recovery.1,8,9
Chromoblastomycosis is caused by dematiaceae fungi and the commonest etiologies are F.
Pedrosoi and C. Carrionii.1,2 Initial lesion may resemble dermatophyta infection or as papule, which develops into nodule, verrucous lesion, exophytic lesion. Another lesion that can be found is a plaque with central atrophy.1,11 Direct examination using 10% KOH can reveal muriform bodies.1,2,11 The treatment may need antifungal agents, which is commonly combined with surgery, cryotherapy and thermotherapy.
Itraconazole and terbinafine for 6-12 months reported good.1,2,11 This paper report SM cases at dr. Cipto Mangunkusumo Nartional Hospital in 1989 - 2013.
Aim
The aim of our study was to identify the type, clinical findings, laboratory work-up and
treatment of SM at the Division of Dermatomycology, Department of Dermatology and Venereology in dr Cipto Mangunkusumo National Hospital between 1989 – 2013 and alsoto study risk factors correlated to SM.
Method
This retrospective study collected data ) from medical records and case reports of patients with SM who came to have treatment at the Division of Dermatomycology, Department of Dermatology and Venereology in dr. Cipto Mangunkusumo National Hospital in 1989 – 2013. The data included sex, age, clinical manifestation, laboratory work-up, diagnosis and treatment. The number of cases found was noted along with the diagnosis and positive results of mycologic examination for each etiology of SM. The type of treatment and response to treatment were also documented.
Results
There were 16 cases of SM at the the Division of Dermatomycology, Department of Dermatology and Venereology in dr. Cipto Mangunkusumo National Hospital between 1989 and 2013, consisted of subcutaneous mucormycosis, mycetoma, actinomycetoma and chromoblastomycosis. Of all SM cases, subcutaneous mucormycosis is the most commonly found case, which were 4 cases and there were 3 cases of chromoblastomycosis.
There was greater number of SM in male compared to female patients with ratio of 3:1.
The most common age group was the age range of 25-44 years as many as 6 subjects. (Table 1, page 7).
Of 16 cases, there were only 12 cases with complete data of clinical examination and laboratory work-up, one of them also did not have treatment data. The most common site for SM lesions is the extremities, which were found in 9 cases of SM and characteristic lesions in 7 cases; 3 cases of subcutaneous mucormycosis, 3 cases of actinomycetoma and 1 case of eumycetoma. (Table 2, page 7).
Direct microscopic examination generally did not reveal any fungal element, except for a case of chromoblastomycosis with black spores. The culture examination revealed Basidiobolus ranarum in all cases of subcutaneous mucormycosis, Nocardia transvalensis in one case of actinomycetoma and Phialophora sp in a case of chromoblastomycosis. On
histopathological examination, we found fine filament granules in four cases of actinomycetoma, coenocytic hyphae in a case of subcutaneous mucormycosis, rough eosinophilic granule and hyphae in a case of mycetoma and black spores in a case of chromoblastomycosis.
(Table 3, page 8).
Most of SM cases that we found were treated with itraconazole. Nevertheless, treatment of SM generally should include a combined therapy with other drugs or with surgery. All cases of subcutaneous mucormycosis treated with itraconazole showed clinical recovery. However, the eumycetoma case which was treated with the therapy showed less satisfying response.
Various types of treatment for SM, either for subcutaneous mucormycosis, chromoblasto- mycosis, actinomycetoma and eumycetoma in dr. Cipto Mangunkusumo National Hospital can be seen in table 4 (page 8).
Of the 16 cases that we found, 3 cases are presented as an illustration.
Case 1. In 2007, there was a case of actinomycetoma with osteomyelitis caused by Nocardia transvalensis. The patient was a 46- year-old man with swollen left foot since 3 years and there was a black spot on the surface of the lesion ( figure 1A, 1B, 1C). The culture examination revealed bacteria, the Nocardia transvalensis (figure 1D). The patient was treated with amikacin, cotrimoxazole and surgery.
Case 2. One subcutaneous mucormycosis case was found in 2012. The patient was a 26-year- old female with hard swelling since 1.5 years on her right arm (figure 2A), right hand(figure 2B, 2C) and right thigh (figure 2D) with no tenderness). On culture examination, we found Basidiobolus sp. The patient was treated with itraconazole for 2 months and had clinical recovery. 14
Case 3. A case of chromoblastomycosis was found in 2012. A male patient aged 47 years had a solitary, verrucous, violaceous-erythematous plaque with a distinctive border and nummular size on physical examination of the lower extremities region and dorsum pedis (figure 3A) of the right foot. The patient had frequent contact with soil and plants at home. The direct microscopical examination revealed muriform- shaped cells (figure 3C). The patient was treated with itraconazole for the first 3 months followed
by a combination therapy with terbinafine. The recovery went slow.15
Discussion
SM is a rare case. There were 16 cases of SM in dr. Cipto Mangunkusumo National Hospital between 1989 and 2013. The types found were subcutaneous mucormycosis, mycetoma, actinomycetoma and chromoblastomycosis. It is rare since SM is a difficult case and frequently undiagnosed or unreported. Ramesh et al found 10 cases of subcutaneous mucormycosis in India between 1999 and 2009 with four children and six adult patients.16 The data from dr. Cipto Mangunkusumo National Hospital showed that there was a greater number of male compared to
female patients. It is similar to the results of SM study in Sanglah Central General Hospital that also found greater number of male than female patients.6 A study by Queiroz-Telles et al. found 71 patients with chromoblastomycosis in Brazil between 1986 and 1996 and they found greater number of male compared to female patients with 12:1 ratio.17 Maiti et al. found 264 cases of mycetoma in India between 1981 and 2000 with 197 cases of actinomycetoma and 67 cases of mycetoma and the male to female ratio was 197:67.18
There are various predisposing factors for SM such as injury that causes contact with the causal fungi.2-4 In most cases, there is a history of injury prior to the development of SM lesions. It is consistent with the results of Queiroz-Telles et al. study that found history of trauma in 45% chromoblastomycosis cases.17 Various activities associated with soil contact such as farming without using footwear, gardening, and mountain climbing can be several factors that affect the development of SM due to microtrauma.2-4 Some cases of SM in dr. Cipto Mangunkusumo National Hospital demonstrate that there are risk factors of SM associated with occupation, those who have hobbies as hikers and history of road traffic Figure 3. A,B. Skin lesion, C. Direct
microscopy examination (muriform cell)
Figure 1. A, B and C. Skin lesion, D. Microscopy cultural examination (Nocardia transvalensis)
Figure 2. A,B. Initial skin lesion; C,D. Skin lesion in 2 months following treatment
accident. A study in Brazil with 325 cases of chromoblastomycosis found that most patients are workers in agricultural or plantation field.17 Similar issue has also been suggested by Maiti et al.18 Londero et al. found the risk of contact with cattle in 35 chromoblastomycosis patients.19 There are challenges in establishing the diagnosis of SM since the facilities for laboratory work-up were not sufficient enough and there were some difficulties to isolate the causative agents. Moreover, there is evidence that one type of fungi can cause different clinical manifestation, which makes the diagnosis difficult.2 In chromoblastomycosis, a lesion may resembles initial dermatophyta infection, it may be a papule, which develops into plaque, nodule, tumor, verrucous lesion and hyperkeratotic lesion. In mycetoma, the mycetoma trias can be found, i.e. subcutaneous nodes, sinus and granules. In subcutaneous mucormycosis, hard swelling of subcutaneous tissue can be found.1-2,4 In one case of chromoblastomycosis, a lesion of tumor accompanied with ulcer was found; while in other case, the lesion was an erythematous plaque. Those clinical findings were not characteristic for chromoblastomycosis. In all cases of subcutaneous mucormycosis, the typical hard swellings were found. However, there were also other atypical lesions in two cases of subcutaneous mucormycosis, such as in the form of dermatitis lesion. The most common site of SM was the extremities, which is consistent with the results of a study by Maiti et al. that found mycetoma lesions on lower extremities in 186 cases.18 A chromoblastomycosis study in Brazil also found that the most common sites were on extremities and foot.17
Identification of microorganism causing SM is difficult, particularly for cases without any granule. In direct microscopy examination at dr.
Cipto Mangunkusumo National Hospital, there was only one case with black spore of chromoblastomycosis. Culture and histopathological examination are very helpful in establishing the diagnosis of SM; however, in most cases, the culture does not always revealed with colony of the causal fungi. On histopathological examination, the typical signs of subcutaneous fungal infection frequently cannot be found. On the culture of one chromoblastomycosis cases, only one
(33%)colony of Phialophora sp was found. The findings is similar to the study of 325 chromoblastomycosis cases in Brazil, which only found F. pedrosoi in 78 (24%) patients’
culture.17 Basidiobolus ranarum was found in all patients with subcutaneous mucormycosis. It is a causal fungus for subcutaneous mucormycosis in children; but, the microorganism can also be the cause of subcutaneous mucormycosis in adults. A study by Ramesh et al. found Basidiobolus ranarum and Syncephalastrum racemosum in subcutaneous mucormycosis cultures.16 In one case of actinomycetoma, Nocardia transvalensis was found in the culture, which is a rare microorganism. Maiti et al. found that Actinomadura sp is the most common cause of actinomycetoma based on the culture results.18 On the histopathological examination of subcutaneous mucormycosis, the splendore- Hoeppli phenomenon could be found, but in one case of subcutaneous mucormycosis, coenocytic hyphae were also found. Fine filament granules were found in four cases of actinomycetoma, rough filament granules were found in one case of mycetoma; while hyphae and black spores were found in one case of chromoblastomycosis.
Treatment of SM may take a long period of time.
It extremely affects with the patient’s compliance to treatment. Different response to SM treatment is also the challenge in SM management.
Subcutaneous mucormycosis therapy using ketoconazole or itraconazole showed good recovery; however, only a few studies have been performed on that issue. Subcutaneous mucormycosis lesions also showed good response to treatment using potassium iodide.1-3 Four cases of subcutaneous mucormycosis were healed using itraconazole treatment. In one case of subcutaneous mucormycosis, which was treated using a combined therapy of itraconazole and potassium iodide, improved lesion was observed within six months. A study by Ramesh et al also found recovery with potassium iodide treatment in patients with subcutaneous mucormycosis in varied period of time between 3 and 9 months of treatment.16 Chromoblastomycosis has a low rate of recovery and with a high relapse rate, particularly in chronic condition. Treatment choices and clinical recovery depend on the causal etiologies, the size and the extent of lesion as well as complications. The treatment management requires antifungal agents, which is commonly combined with surgery, cryotherapy and thermotherapy. A study reported various rate of clinical and mycological recovery of
chromoblastomycosis ranges between 15-80%.4 A chromoblastomycosis case was treated with combined itraconazole and terbinafine as additional therapy; however, the lesion still developed. The treatment of mycetoma is difficult and it frequently needs a combination of pharmacological treatment and surgery. The degree of severity and duration of illness determine the success of therapy. It is better to treat small lesion with surgery. Pharmacological treatment is frequently difficult as there are different responses to antifungal agents.
Itraconazole and terbinafine are considered as alternatives of treatment for eumycetoma.1,4 In one case of eumycetoma treated with itraconazole, showed an improvement, but the lesion was relapsed. Three other actinomycetoma cases treated with amikacin and cotrimoxazole as well as surgical treatment, with good recovery rate.
Conclusion
SM cases in the Department of Dermatology and Venereology dr. Cipto Mangunkusumo Hospital are very rare. Most cases are dominated by male patients with varied ages. Diagnosis of SM is difficult, which becomes a challenge in management and predicting the prognosis of patients. Histopathological examination has an important role in establishing the diagnosis.
Complete laboratory work up, multidisciplinary collaboration, along with comprehensive treatment is necessary in the management of SM.
Reference
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Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, editor. Fitzpatrick’s dermatology in general medicine. 8th ed.
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fungal infections. Curr Infect Dis Rep.
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Classification of subcutaneous and systemic mycoses. Clin Dermatol .2012;30(4):369-71.
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Subcutaneous fungal infections. Dermatol Ther.2004;17(6):523-531.
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Subcutaneous mycosis profunda profile in Sanglah Hospital Denpasar. Procedding of the 11th Annual Scientific Meeting Indonesia Scociety of Dermatology and Venereology, 2010 June 22-23; Bali.
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1988:249-68.
12. Statistic Reports. Mycology Division.
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Procedding of the Scientific Meeting and National Congress Indonesia Society for Medical Mycology, 2013 June 29-30; Bandung 14. Chairunnisa S. Multiple and extensive
subcutaneous zigomycosis treated with potassium iodide and itraconazole as combination therapy. Procedding of the 12th Annual Scientific Meeting Indonesia Society of Dermatology and Venereology, 2012 June 21-23; Solo
15. Olivia T. Chromoblastomycosis with multiple lesions. Procedding of the 12th Annual Scientific Meeting Indonesia Society of Dermatology and Venereology, 2012 June 21-23; Solo
16. Ramesh V, Ramam M, Capoor MR, Sugandhan S, Dhawan J, Khanna G.
Subcutaneous zygomycosis: Report of 10 cases from two institutions in North India.
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Table 1. Sociodemographic characteristic of subcutaneous mycosis patients in dr. Cipto Mangunkusumo National Hospital in 1989-2013 (number = 16)
No. Characteristic Total
1. Gender Male Female
12 4 2. Age group (year)
5-14 15-24 25-44 45-64
>65
3 1 6 4 2 3. Occupation/activities
Activities associated with soil contact Activities not associated with soil contact Not known
6 4 6 4. Origin
Jakarta
Besides Jakarta Not known
5 5 6
Table 2. Clinical manifestation of SM patients in dr. Cipto Mangunkusumo National Hospital in 1989- 2013 (number =16)
No. Diagnosis
Lesions Not known
Characteristic Less Characteristic
1. Subcutaneous mucormycosis 3 2 0
2. Chromoblastomycosis 0 2 1
3. Actinomycetoma 3 1 0
4. Eumycetoma 1 0 3
TOTAL 7 5 4
Table 3. Laboratory work-up for patients with subcutaneous mycosis in dr. Cipto Mangunkusumo National Hospital in 1989-2013(Number =16)
No
. Diagnosis
Direct microscopic examination
Histopathological examination
Culture
Θ Not found Θ Not found Θ Not found
1. Subcutaneous
mucormycosis 0 0 5# 1** 4 0 5† 0 0
2. Chromoblastomy
cosis 1* 1 1 2 0 1 1≠ 1 1
3. Actinomycetoma 0 4 0 3 0 0 1π 2 1
4. Eumycetoma 0 1 3 1 0 3 0 1 3
Total 1 6 9 7 4 4 7 4 5
Note: =positive, Θ=negative # Not performed, * black spores, ** coenocytic hyphae, † Basidiobolus ranarum, ≠ Nocardia transvalensis, π Phialophora sp
Table 4. Treatment and response to therapy for SM patients in dr. Cipto Mangunkusumo National Hospital, 1989 – 2013
No. Diagnosis
Antifungal therapy Other procedures Response
Drugs N Procedures N Final
response
N
1. Subcutaneous mucormycosis
Itraconazole 4 - - Clinical
recovery
4 Itraconazole
& potassium iodide
1 - - Clinical
recovery
1
2. Chromoblastomyc osis
Itraconazole, fluconazole
1 - - Less satisfying
response, loss to follow up
1 Itraconazole,
terbinafin
1 Heat
Therapy
1 Not showing clinical recovery loss
to follow up 1
Not Known 1 - -
3. Actinomycetoma
Amikasin, cotrimoxazole
3 Surgery 3 Clinical
recovery
3
- 1 - -
4. Eumycetoma
Itraconazole, Amoxcycillin cluvanic acid
1 - - Less satisfying
response loss to follow up
1
Not Known 3 - -
N=Number of cases
A B C D