• Users Online: 661
  • Print this page
  • Email this page


 
  Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  Issue : 3  |  Page : 256-261  

Mycetoma: A common yet unrecognized health burden in central India


1 Department of Dermatology, Venereology and Leprology, Government Medical College, Nagpur, Maharashtra, India
2 Department of Pathology, Government Medical College, Nagpur, Maharashtra, India
3 Department of Microbiology, Vasantrao Naik Government Medical College, Yavatmal, Maharashtra, India

Date of Web Publication17-May-2019

Correspondence Address:
Vaishali H Wankhade
Department of Dermatology, Venereology and Leprology, Government Medical College and Hospital, Nagpur - 440 003, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/idoj.IDOJ_358_18

Rights and Permissions
   Abstract 


Context: Mycetoma is a chronic suppurative infective disorder of skin, subcutaneous tissue, fascia, and bones caused by the traumatic inoculation of either fungal (eumycotic) or bacterial (actinomycotic) organisms present in the soil. Triad of tumefaction, discharging sinuses, and grains characterizes the disease. Aims: This study was undertaken to study the clinical spectrum and treatment response of mycetoma in central India. Settings and Design: It was a retrospective study of clinical and/or biopsy-proven and treated cases of mycetoma from November 2015 to October 2016. Subjects and Methods: Medical records of diagnosed and treated mycetoma patients were enrolled retrospectively during November 2015 and October 2016. Case records of patients were evaluated with respect to demographic, clinical, microbiological details, bone involvement, and treatment. Type of therapies and outcome, wherever available, were also assessed. Statistical Analysis: Statistical analysis was done using proportion, mean, and percentages. Results: Eleven cases (male = 8) were seen during the study period (seven actinomycetoma and four eumycetoma). Foot and lower extremity was the most common site (9/11), whereas upper extremity and forehead were involved in one case each. On culture, the organisms isolated were Phialophora and Fusarium. Modified Welsch regimen was started in six of seven patients with actinomycetoma, whereas one was started on sulfamethoxazole–trimethoprim and a combination of amoxicillin and clavulanic acid therapy. All four cases of eumycetoma were treated with itraconazole. On follow-up, six cases of actinomycetoma cases showed significant improvement. Two cases of eumycetoma showed mild to moderate improvement and one case required surgical intervention. One case each of actinomycetoma and eumycetoma were lost to follow-up. Conclusion: Mycetoma has been recognized as a neglected tropical disease by the World Health Organization, recently. There are very few case reports from the central part of India. Prominent case detection in our study emphasizes the need of larger studies to know the extent of disease in this part of India.

Keywords: Actinomycetoma, eumycetoma, itraconazole, modified Welsh regimen


How to cite this article:
Sawatkar GU, Wankhade VH, Supekar BB, Pratap RP, Bhat DM, Tankhiwale SS. Mycetoma: A common yet unrecognized health burden in central India. Indian Dermatol Online J 2019;10:256-61

How to cite this URL:
Sawatkar GU, Wankhade VH, Supekar BB, Pratap RP, Bhat DM, Tankhiwale SS. Mycetoma: A common yet unrecognized health burden in central India. Indian Dermatol Online J [serial online] 2019 [cited 2019 Jun 27];10:256-61. Available from: http://www.idoj.in/text.asp?2019/10/3/256/258607




   Introduction Top


Mycetoma is a chronic infectious disease of the skin, subcutaneous tissue, and bone with high morbidity. The lesion is characterized by the triad of tumefaction, discharging sinuses, and the grains that are formed by the colonies of causal organisms. Depending on the organism, it can be either actinomycotic or eumycotic. The disease is common in people with low socioeconomic status, mostly who are field workers. Although it is prevalent worldwide, it continues to be a major health problem in the tropical and subtropical countries such as India.[1],[2],[3]

Dry areas are more facilitative for actinomycetoma, whereas eumycetoma is more common in areas with more rainfall.[3] Within India, there is wide variation in the cases, as eumycetoma is common in Rajasthan, whereas other states, namely, Andhra Pradesh, Punjab, Madhya Pradesh, Tamil Nadu, and West Bengal report most cases of actinomycetoma.[2] However, there is a dearth in literature regarding the exact epidemiology of the cases due to lack to reporting. Herein, we present our experience of cases of mycetoma which we came across at the Government Medical Institute, Nagpur (Maharashtra), which is in the central part of India.


   Subjects and Methods Top


It was a retrospective study of clinically suspicious cases of mycetoma from November 2015 to October 2016. Institutional ethical committee clearance was taken. Clinical diagnosis was made by the classic triad of tumefaction, discharging sinuses, and presence of grains. Case records of patients were evaluated with respect to age, gender, occupation, site of involvement, duration of disease, and bone involvement. KOH, Gram stain, Periodic acid–Schiff stain, fine-needle aspiration cytology, and biopsy were performed in all cases. Imaging modalities such as X-ray, ultrasonography, and MRI were performed wherever applicable. Categorization of the lesion into eumycotic or actinomycotic was based on either clinical and/or histopathological and culture characteristics. Microbiological parameters such as grain size, color (by direct examination with 10% KOH), and culture results were correlated wherever available. All patients with eumycetoma were treated with itraconazole 400 mg daily. Six patients with actinomycetoma were treated with modified welsh regimen.[4] Each cycle comprised amikacin (15 mg/kg/day) in two divided doses 12 h apart for 21 days at a interval of 15 days along with daily administration of sulfamethoxazole–trimethoprim (35 + 7 mg/kg/day) and rifampicin at a dose of 10 mg/kg/day.[4] Six patients with actnomycetoma received five such cycles. The demographic details, clinicopathological, microbiological, and therapeutic outcome data of all 11 patients are represented in [Table 1] and [Table 2]. Statically analysis was done using mean, median, and proportion.
Table 1: Demographic details and clinical history details

Click here to view
Table 2: Investigation details, treatment details, and outcome

Click here to view



   Results Top


Seven patients belonged to Nagpur city and its rural area, whereas two patients each belonged to the adjacent states of Madhya Pradesh (Balaghat) and Chhattisgarh (Rajnandgaon). Among the 11 patients, 7 cases were of actinomycetoma (actinomycetoma: eumycetoma = 7:4). The male-to-female ratio was 8:3 with a mean age of patients being 32 years (age range = 18–55 years). The average duration of reporting to our institute was 43.2 months (range = 8–120 months). Foot and lower extremity was the most common site of involvement (9/11) [Figure 1]a and [Figure 1]b. Upper extremity and forehead were involved in one patient each [Figure 1]c and [Figure 1]d. Black grains were isolated in three patients and KOH, examination of which showed fungal elements, suggestive of eumycetoma [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Histopathology from discharging sinuses of clinically suspected eumycotic lesion revealed sulfur granule showing thick septate hyphae at the periphery of granules surrounded by infiltrate comprising lymphoid cells, histiocytes, neutrophils, eosinophils, plasma cells, and fibroblasts in deep reticular dermis [Figure 3]a and [Figure 3]b. Biopsy taken from the discharging sinuses of actinomycotic lesion revealed epidermis with acanthosis and irregular colony comprising filamentous bacteria surrounded by mixed inflammatory cells in dermis [Figure 4]a and [Figure 4]b. Culture was done in all patients and was positive only in two patients with eumycetoma. Fungal growth of two organisms, namely, Exophiala jeanselmei and Fusarium, were identified on sabouraud dextrose agar culture. Slide culture of E.jeanselmei species showed septate hyphae with tubular conidiophore bearing clusters of conidia at the tips and also along the sides of hyphae [Figure 5]a and [Figure 5]b. Slide culture of Fusarium species showed septate hyphae with sickle-shaped multiseptate macroconidia [Figure 5]c and [Figure 5]d. All patients with actinomycetoma and one case of eumycetoma had underlying bone involvement. Ill-defined permeative pattern of bony destruction along with soft tissue swelling was the most common radiological finding [Figure 6]a and [Figure 6]b. Modified Welsh regimen was initiated in six patients with actinomycetoma, whereas one pregnant patient was treated with sulfamethoxazole–trimethoprim and a combination of amoxicillin and clavulanic acid therapy.
Figure 1: Swelling with multiple discharging sinuses of foot (a), lower leg (b), upper extremity (c), and forehead (d)

Click here to view
Figure 2: Black grains isolated from discharging sinuses over dosum of foot (a), plantar aspect of foot (b and c), and fungal elements seen on KOH examination of grains suggestive of eumycetoma(d)

Click here to view
Figure 3: (a and b) Histopathology from discharging sinuses of clinically suspected eumycotic lesion revealed sulfur granule showing thick septate hyphae at the periphery of granules surrounded by infiltrate comprising lymphoid cells, histiocytes, neutrophils, eosinophils, plasma cells, and fibroblasts in deep reticular dermis (×40, ×100)

Click here to view
Figure 4: (a and b) Biopsy taken from discharging sinuses of actinomycotic lesion revealed epidermis with acanthosis and irregular colony comprising filamentous bacteria surrounded by mixed inflammatory cells in dermis (×40, ×100)

Click here to view
Figure 5: (a and b) Slide culture of Exophiala jeanselmei species showing septate hyphae with tubular conidiophore bearing clusters of conidia at the tips and also along the sides of hyphae. (c and d) Slide culture of Fusarium species showing septate hyphae with sickle-shaped multiseptate macroconidia

Click here to view
Figure 6: Ill-defined permeative pattern of bony destruction along with soft tissue swelling over upper tibia (a) and talus, calcaneum, and cuboid bones (b)

Click here to view


All four patients with eumycetoma were treated with oral itraconazole at a dose of 400 mg daily. On follow-up, six patients with actinomycetoma showed significant improvement after five cycles of modified Welsh regimen [Figure 7]a, [Figure 7]b, [Figure 7]c, [Figure 7]d. Two patients with eumycetoma showed moderate improvement [Figure 8]a and [Figure 8]b. Surgical debridement was required in one patient with eumycetoma. One case each of actinomycetoma and eumycetoma were lost to follow-up.
Figure 7: Pretreatment and posttreatment images of case of actinomycetoma over right knee (a and b) and right leg lesions (c and d)

Click here to view
Figure 8: Pretreatment (a) and posttreatment (b) images of case of eumycetoma over foot

Click here to view



   Discussion Top


Mycetoma, caused by bacteria (actinomycetoma) or fungi (eumycetoma), is a devastating, neglected tropical disease characterised by extensive tissue destruction, deformities, and disabilities in the affected patients.[5] It is also commonly referred as “Madura Foot” as it was first described in Madurai in South India, in 1842. It typically affects poor communities in the tropical and subtropical belt such as Sudan, Mexico, and India.[3] Prevalence of mycetoma can be generalized over these countries except one, India.[2] These may be because of the variation in the climate, socioeconomic factors, and the variations in reporting in the literature.

The male-to-female ratio of mycetoma ranges from 1.6 to 6.6:1 in adults,[6],[7],[8] a finding similar to ours. Mycetoma is predominantly a disease of men in rural areas, who work barefoot, putting them at a greater risk of acquiring trauma and infection by these pathogens. As the disease does not produce pain or any other discomfort, it usually goes unnoticed for a long period of time, until it produces a significant deformity. Poor hygiene, low socioeconomic status, and low nutrition are the suggested risk factors. Although mycetoma is generally considered a disease of second to fourth decade, children and adolescents can also be affected in endemic countries.[4],[9],[10]

In this series, seven were farmers and field laborers by occupation, whereas other three were students and one was driver. A strong history of injury was available only in three patients. The average duration of reporting was found to be 43.2 months (range = 8–120 months). This can be ascribed to asymptomatic, painless, slow progressive nature of the disease, low health education, improper/inadequate treatment from local healthcare provider and social stigma associated with the disease.

Foot and lower extremities followed by hand have been mentioned as the commonest sites of mycetoma.[4] In our series, seven patients had involvement of foot, two had involvement of knee, one had involvement of right forearm, and one had involvement of forehead. Involvement of uncommon sites such as upper extremity, trunk, buttocks, face, head, and neck [4],[11],[12] suggest that mycetoma is not just a disease of lower extremities. It further highlights that if prompt diagnosis and treatment is not made, then deformity is certain. The majority of published literature on mycetoma showed actinomycetoma outnumbering eumycetoma cases which correlated with our study (7:4).[13] The common organisms causing mycetoma in the Indian scenario are Actinomadura madurae, Nippostrongylus brasiliensis, and Actinomadura pelletieri. However, we could only get growth of Phialophora and Fusarium in our series. Cultures for all cases of actinomycetoma were negative. Bakshi and Mathur found Madurella mycetomatis as the most common eumycotic agent in their histopathological analysis.[14] Padhi et al. found Madurella mycetomatis, Neoscytalidium dimidiatum, and Aspergillus flavus as the most common agent of eumycetoma.[13] Precise identification of causative organism was difficult in our setup due to lack of facilities and/or partial treatment of patients from outside, stringent growth requirements, as well as the small numbers of viable organisms present in a long-standing, inflammatory lesion. Radiological findings of bone involvement include periosteal erosion secondary to invasion, osteoporosis, and changes consistent with osteomyelitis, osteolysis, and osteosclerosis. Subtle radiographic features such as few, larger (≥1 cm in diameter) lytic lesions prompt toward eumycetoma, whereas multiple, smaller lytic lesions are found in actinomycetoma.[9]

Polymerase chain reaction (PCR) is rapid and inexpensive method used in diagnosis of mycetoma. PCR is done directly on the biopsy specimen, and sequencing of gene regions, for example, internal transcribed spacer 1 (ITS1) and ITS2, is usually sufficient in most isolated fungi.[15] But this facility is not available at our institution.

Complete therapeutic cure of mycetoma is a major challenge. Actinomycetomas are usually well-responsive to antibiotic treatment. Several antibiotics such as cotrimoxazole, dapsone, streptomycin, trimethoprim, rifampicin, and amoxicillin–clavulanic acid combination have been used and found to be effective.[16] Various regimens such as Ramam regime, modified Ramam, Welsh regime, and modified Welsh regime have been found to be effective in treatment of actinomycetoma. Irrespective of the regime used, the duration of treatment is individualized and depends on the clinical response to treatment. The number of cycles of Welsh regimen can be three only if soft tissue involvement is present and can be increased to five in case of bone involvement.[9] In our case series, six patients with actinomycetoma showed significant improvement after five cycles of modified Welsh regimen. One case of actinomycetoma lost to follow-up.

Eumycetoma is refractory to treatment, and no standard guidelines or regime are available at present. Itraconazole is being used but is unable to eradicate the fungus and needs to be given for a longer duration and is expensive. Voriconazole and posaconazole have been assessed in a very limited number of patients with some promising results. Isavuconazole and fosravuconazole were reported to have excellent in vitro activity. Amputations and recurrences in patients with eumycetoma are common.[3] Oral itraconazole showed mild to moderate improvement, though surgical intervention was required in one case with eumycetoma. Long duration of treatment is another important factor for noncompliance of patients to follow-up. Similarly, in our series two patients were lost to follow-up. This emphasizes the importance of proper counseling of such patients.


   Conclusion Top


Among the 11 patients, 7 cases were of actinomycetoma (actinomycetoma: eumycetoma = 7:4), in our study. This prominent case detection in a short period of time signifies burden of mycetoma in this part of Maharashtra. A radiological screening should be done in all cases of mycetoma as it is one of the most important factors determining the duration of treatment. Modified Welsh regimen showed excellent response in all of our cases of actinomycetoma and can be considered as first-line therapy for the same. Precise identification of organisms by newer diagnostic techniques such as PCR can lead to better treatment outcomes reducing the disability and disfigurement associated with this condition. To the best of our knowledge, this is the first study of mycetoma from the central part of India.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Reddy CR, Sundareshwar B, Rao AP, Reddy SS. Mycetoma – Histopathological diagnosis of causal agents in 50 cases. Indian J Med Sci 1972;26:733-6.  Back to cited text no. 1
    
2.
Van de Sande WW. Global burden of human mycetoma: A systematic review and meta-analysis. PLoS Negl Trop Dis 2013;7:e2550.  Back to cited text no. 2
    
3.
Zijlstra EE, van de Sande WW, Welsh O, Mahgoub el S, Goodfellow M, Fahal AH. Mycetoma: A unique neglected tropical disease. Lancet Infect Dis 2016;16:100-12.  Back to cited text no. 3
    
4.
Damle DK, Mahajan PM, Pradhan SN, Belgaumkar VA, Gosavi AP, Tolat SN, et al. Modified Welsh regimen: A promising therapy for actinomycetoma. J Drugs Dermatol 2008;7:853-6.  Back to cited text no. 4
    
5.
Omer RF, Seif El Din N, Abdel Rahim FA, Fahal AH. Hand mycetoma: The mycetoma research centre experience and literature review. PLoS Negl Trop Dis 2016;10:e0004886.  Back to cited text no. 5
    
6.
Castro LG, Piquero-Casals J. Clinical and mycologic findings and therapeutic outcome of 27 mycetoma patients from Sao Paulo, Brazil. Int J Dermatol 2008;47:160-3.  Back to cited text no. 6
    
7.
Fahal AH. Mycetoma: A thorn in the flesh. Trans R Soc Trop Med Hyg 2004;98:3-11.  Back to cited text no. 7
    
8.
Zarei Mahmoudabadi A, Zarrin M. Mycetomas in Iran: A review article. Mycopathologia 2008;165:135-41.  Back to cited text no. 8
    
9.
Sawatkar GU, Narang T, Shiva Prakash MR, Daroach M, Sharma M, Nahar Saikia U, et al. Aspergillus: An uncommon pathogen of eumycetoma. Dermatol Ther 2017;30.  Back to cited text no. 9
    
10.
Agarwal US, Besarwal RK, Gupta R, Agarwal P. Treatment of actinomycetoma foot – Our experience with ten patients. J Eur Acad Dermatol Venereol 2013;27:1505-13.  Back to cited text no. 10
    
11.
Dhingra M, Kaistha N, Bansal N, Solanki LS, Chander J, Thami GP, et al. Nocardia nova mycetoma over forehead in a lepromatous leprosy patient. Dermatol Online J 2012;18:3.  Back to cited text no. 11
    
12.
Fahal A, Mahgoub el S, El Hassan AM, Jacoub AO, Hassan D. Head and neck mycetoma: The mycetoma research centre experience. PLoS Negl Trop Dis 2015;9:e0003587.  Back to cited text no. 12
    
13.
Padhi S, Uppin SG, Uppin MS, Umabala P, Challa S, Laxmi V, et al. Mycetoma in South India: Retrospective analysis of 13 cases and description of two cases caused by unusual pathogens: Neoscytalidium dimidiatum and Aspergillus flavus. Int J Dermatol 2010;49:1289-96.  Back to cited text no. 13
    
14.
Bakshi R, Mathur DR. Incidence and changing pattern of mycetoma in western Rajasthan. Indian J Pathol Microbiol 2008;51:154-5.  Back to cited text no. 14
[PUBMED]  [Full text]  
15.
Ahmed AO, Mukhtar MM, Kools-Sijmons M, Fahal AH, de Hoog S, van den EndeBG, et al. Development of a species-specific PCR-restriction fragment length polymorphism analysis procedure for identification of Madurella mycetomatis. J Clin Microbiol 1999;37:3175-8.  Back to cited text no. 15
    
16.
Welsh O, Sauceda E, Gonzalez J, Ocampo J. Amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of actinomycotic mycetoma. J Am Acad Dermatol 1987;17:44.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Subjects and Methods
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed157    
    Printed2    
    Emailed0    
    PDF Downloaded48    
    Comments [Add]    

Recommend this journal