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White Grain Mycetoma Caused by Scedosporium apiospermum in North India: A Case Report Munesh Kumar Gupta, Tuhina Banerjee, Dhirendra Kumar, Amit Rastogi and Ragini Tilak International Journal of Lower Extremity Wounds 2013 12: 286 DOI: 10.1177/1534734613512504 The online version of this article can be found at: http://ijl.sagepub.com/content/12/4/286
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512504
research-article2013
IJLXXX10.1177/1534734613512504The International Journal of Lower Extremity WoundsGupta et al
Case Report
White Grain Mycetoma Caused by Scedosporium apiospermum in North India: A Case Report
The International Journal of Lower Extremity Wounds 12(4) 286–288 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1534734613512504 ijl.sagepub.com
Munesh Kumar Gupta, MBBS1, Tuhina Banerjee, MBBS, MD1, Dhirendra Kumar, MBBS1, Amit Rastogi, MBBS, MS2, and Ragini Tilak, MBBS, MD1
Abstract Mycetoma is chronic granulomatous infection of skin and subcutaneous tissue caused by both bacteria and fungi. We report a case of mycetoma caused by Scedosporium apiospermum in the right foot of a 45-year-old farmer in north India. The patient had a history of trauma in the sole of the right foot followed by discharge of white granules along with proximal progression. Scedosporium apiospermum was identified based on colony characteristics and microscopic features on slide culture. Mycetoma is a progressive disease. Foot is commonly affected in persons who walk barefoot, especially in south India. Untreated mycetoma progress and involve the underlying fasciae and tissues along with bones often resulting in loss of limb. By prompt and reliable diagnosis with corresponding antimicrobial administration, we can prevent further progression and limb disability. Keywords mycetoma, Scedosporium, white grain, foot, India Mycetoma, originally described by John Gill as Madura foot or Maduramycosis, is a chronic, slowly progressive, granulomatous infection caused by Actinomycetes and fungi. It is endemic in tropical and subtropical countries like India, where it mostly affects the dorsal aspect of forefoot of young adults 20 to 40 years old as these are highly prone to repeated trauma.1-3 It is characterized by triad of tumefaction of affected tissue, presence of multiple discharging sinuses with presence of granules. Granules are the aggregation of the causative microorganism with affected tissues that come out through the sinus tract.
Case Presentation A 45-year-old farmer from a rural area in north India presented to the Dermatology Outpatient Department of a tertiary care centre with complaints of swelling in the right foot. He had a history of trauma in the right sole while farming, 7 years ago. According to him, a nodule had appeared at the affected site for which he took some antibiotic treatment and got relief. Later, there was progressively increasing nodule with presence of multiple discharging sinuses (Figure 1), with intermittent oozing of granular substances from these sinuses. As before, he underwent some consultation from a local doctor but failed to have any response.
At the time of presentation, firm to hard swelling involving his forefoot of right leg with multiple discharging sinuses was seen. Opening of the sinuses were black dotted. There was oozing out of white-colored granules. Laboratory reports were as follows. X-ray imaging revealed involvement of the bones, including tarsal and metatarsal bones (Figure 2). On histopathological examination, there was acanthosis of the cells with signs of chronic inflammation. For laboratory workup, affected area was cleaned with 70% alcohol and pus sample was collected. White-colored granules were oozed out. The pus sample was processed for microbiological evaluation namely Gram’s staining, modified Ziehl Neelsen staining (using 1% acid decolorizer), and 10% potassium hydroxide (KOH) wet mount. Sample was directly inoculated on Sabouraud’s dextrose agar at 25°C and 37°C in the biochemical oxygen demand incubator. The sample was also directly inoculated on blood agar, Lowenstein Jensen media, and brain heart infusion broth (HiMedia Laboratories, Mumbai, India). 1
Dept. of Microbiology, IMS, Banaras Hindu University, Varanasi, India Dept. of Orthopaedics, IMS, Banaras Hindu University, Varanasi, India
2
Corresponding Author: Ragini Tilak, Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. Email: [email protected]
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Gupta et al
Figure-3. Hyaline fungal hyphae on potassium hydroxide (KOH) examination. Figure 1. Lower limb with multiple discharging sinuses.
Figure-4. Fungal hyphae on hematoxylin and eosin staining. Figure 2. X-ray image of lower limb showing involvement of tarsal and metatarsal bones.
On Gram’s staining, presence of pus cells was seen. No acid fast structure was seen. On 10% KOH wet mount, hyaline fungal hyphae were seen (Figure 3). The white-colored granules oozing out were 0.5 to 1 mm in size without any cement-like matrix. The granules were processed for Gram’s staining but failed to reveal any filamentous structure. On hematoxylin and eosin staining, fungal hyphae were observed (Figure 4). On Sabouraud’s dextrose agar, texture of the growth was cottony and moist initially, which became flat with fine, short, mycelial tufts later. On obverse view, color of the colony was light gray, which became dark gray to black as the colony matured. Reverse was gray to black at 25°C in the biochemical oxygen demand incubator.
Slide culture was done that revealed hyaline and septate hyphae on lactophenol mount. Conidogenous cells (annellides) were seen to arise directly from the hyphae. Conidia were unicellularly present at the apex of these annellides. A diagnosis of white grain mycetoma caused by S apiospermum was made. However, on the basis of KOH wet mount results and before the complete identification of the isolate, fluconazole (400 mg/d) was started empirically and the patient was advised to have follow-up after 15 days but failed to do so.
Discussion Eumycetoma is caused by filamentous fungi. Eumycetoma is classified according to the color—black or white—of the
Downloaded from ijl.sagepub.com at Scientific library of Moscow State University on January 16, 2014
288
The International Journal of Lower Extremity Wounds 12(4)
granules oozing out. Black grain mycetoma is quite common in south India in contrast to white grain mycetoma, which is common in north India. It usually affects the extremities, exposed parts like foot or hand. Chronic infection of the tissue leads to hard swollen mass with multiple discharging sinuses and oozing of granules. Superimposed bacterial infections also complicate the clinical outcome. In this report, we describe a case of white grain mycetoma caused by S apiospermum at a tertiary center in north India. Few cases of S apiospermum mycetoma have been reported from north India. Pseudoallescheria boydii is the teleomorphic stage of S apiospermum and a frequent cause of white grain mycetoma. This cosmopolitan fungus enters the tissues following penetrating injury. After subcutaneous inoculation of fungi, it proliferates and involves muscles and tissues underneath.4 Despite having gray-black-colored growth and brown-black conidia, the hyphae of S apiospermum are hyaline. Even Fontana-Masson staining is negative for melanin.5 Granules of S apiospermum are 1 to 2 mm, soft, irregular and white colored6 and surrounded by a eosinophilic fringe.7 Antifungal drugs, including amphotericin B, itraconazole, ketoconazole, and flucytosine have low in vitro efficacy against this fungus.8-14 However, voriconazole and ravuconazole are moderately effective.15 Amphotericin B and micafungin combination have synergistic effect against this fungus16 as micafungin, echinocandin, inhibit the (1,3)-β-d-glucan synthase, thus interfering with fungal cells.17,18 Amphotericin B becomes active in low dose once there is altered cell wall structure. Often a combination therapy of amphotericin B and micafungin is required for effective management of this highly resistant fungus and for its prompt identification. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Develoux M, Ndiaye B, Dieng MT. Mycetomas in Africa [in French]. Sante. 1995;5:211-217. 2. N’diaye B, Develoux M, Dieng MT, et al. Aspects actuels des mycétomes au Sénégal. A propos de 109 cas [in French]. J Mycol Méd. 2000;10:140-144. 3. Fahal AH. Mycetoma: a thorn in the flesh. Trans R Soc Med Hyg. 2004;98:3-11.
4. Grover CRN. Case presentation. Johns Hopkins Microbiol Newslett. 1997;16:13. 5. Kimura M, McGinnis MR. Fontana-Masson–stained tissue from culture-proven mycoses. Arch Pathol Lab Med. 1998;122:1107-1111. 6. Rippon JW. Medical Mycology. The Pathogenic Fungi and the Pathogenic Actinomycetes. 3rd ed. Philadelphia, PA: W.B. Saunders; 1998. 7. Hay RJ, Mackenzie DW. The histopathological features of pale grain eumycetoma. Trans R Soc Trop Med Hyg. 1982;76:839-844. 8. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother. 2001;45:2151-2153. 9. Cuenca-Estrella M, Ruiz-Díez B, Martínez-Suárez JV, Monzón A, Rodríguez-Tudela JL. Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. J Antimicrob Chemother. 1999;43:149-151. 10. Espinel-Ingroff A. In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J Clin Microbiol. 1998;36:198-202. 11. Meletiadis J, Meis JF, Mouton JW, Rodriquez-Tudela JL, Donnelly JP, Verweij PE; EUROFUNG Network. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob Agents Chemother. 2002;46:62-68. 12. Minassian B, Huczko E, Washo T, Bonner D, Fung-Tomc J. In vitro activity of ravuconazole against Zygomycetes, Scedosporium and Fusarium isolates. Clin Microbiol Infect. 2003;9:1250-1252. 13. Odabasi Z, Paetznick VL, Rodriguez JR, Chen E, OstroskyZeichner L. In vitro activity of anidulafungin against selected clinically important mold isolates. Antimicrob Agents Chemother. 2004;48:1912-1915. 14. Pfaller MA, Marco F, Messer SA, Jones RN. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis. 1998;30:251-255. 15. Radford SA, Johnson EM, Warnock DW. In vitro studies of activity of voriconazole (UK-109,496), a new triazole antifungal agent, against emerging and less-common mold pathogens. Antimicrob Agents Chemother. 1997;41:841-843. 16. Yustes C, Guarro J. In vitro synergistic interaction between amphotericin B and micafungin against Scedosporium spp. Antimicrob Agents Chemother. 2005;49:3498-3500. 17. Hatano K, Morishita Y, Nakai T, Ikeda F. Antifungal mechanism of FK463 against Candida albicans and Aspergillus fumigatus. J Antibiot (Tokyo). 2002;55:219-222. 18. Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362:1142-1151.
Downloaded from ijl.sagepub.com at Scientific library of Moscow State University on January 16, 2014
White Grain Mycetoma Caused by Scedosporium apiospermum in North India: A Case Report Munesh Kumar Gupta, Tuhina Banerjee, Dhirendra Kumar, Amit Rastogi and Ragini Tilak International Journal of Lower Extremity Wounds 2013 12: 286 DOI: 10.1177/1534734613512504 The online version of this article can be found at: http://ijl.sagepub.com/content/12/4/286
Published by: http://www.sagepublications.com
Additional services and information for The International Journal of Lower Extremity Wounds can be found at: Email Alerts: http://ijl.sagepub.com/cgi/alerts Subscriptions: http://ijl.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Dec 17, 2013 What is This?
Downloaded from ijl.sagepub.com at Scientific library of Moscow State University on January 16, 2014
512504
research-article2013
IJLXXX10.1177/1534734613512504The International Journal of Lower Extremity WoundsGupta et al
Case Report
White Grain Mycetoma Caused by Scedosporium apiospermum in North India: A Case Report
The International Journal of Lower Extremity Wounds 12(4) 286–288 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1534734613512504 ijl.sagepub.com
Munesh Kumar Gupta, MBBS1, Tuhina Banerjee, MBBS, MD1, Dhirendra Kumar, MBBS1, Amit Rastogi, MBBS, MS2, and Ragini Tilak, MBBS, MD1
Abstract Mycetoma is chronic granulomatous infection of skin and subcutaneous tissue caused by both bacteria and fungi. We report a case of mycetoma caused by Scedosporium apiospermum in the right foot of a 45-year-old farmer in north India. The patient had a history of trauma in the sole of the right foot followed by discharge of white granules along with proximal progression. Scedosporium apiospermum was identified based on colony characteristics and microscopic features on slide culture. Mycetoma is a progressive disease. Foot is commonly affected in persons who walk barefoot, especially in south India. Untreated mycetoma progress and involve the underlying fasciae and tissues along with bones often resulting in loss of limb. By prompt and reliable diagnosis with corresponding antimicrobial administration, we can prevent further progression and limb disability. Keywords mycetoma, Scedosporium, white grain, foot, India Mycetoma, originally described by John Gill as Madura foot or Maduramycosis, is a chronic, slowly progressive, granulomatous infection caused by Actinomycetes and fungi. It is endemic in tropical and subtropical countries like India, where it mostly affects the dorsal aspect of forefoot of young adults 20 to 40 years old as these are highly prone to repeated trauma.1-3 It is characterized by triad of tumefaction of affected tissue, presence of multiple discharging sinuses with presence of granules. Granules are the aggregation of the causative microorganism with affected tissues that come out through the sinus tract.
Case Presentation A 45-year-old farmer from a rural area in north India presented to the Dermatology Outpatient Department of a tertiary care centre with complaints of swelling in the right foot. He had a history of trauma in the right sole while farming, 7 years ago. According to him, a nodule had appeared at the affected site for which he took some antibiotic treatment and got relief. Later, there was progressively increasing nodule with presence of multiple discharging sinuses (Figure 1), with intermittent oozing of granular substances from these sinuses. As before, he underwent some consultation from a local doctor but failed to have any response.
At the time of presentation, firm to hard swelling involving his forefoot of right leg with multiple discharging sinuses was seen. Opening of the sinuses were black dotted. There was oozing out of white-colored granules. Laboratory reports were as follows. X-ray imaging revealed involvement of the bones, including tarsal and metatarsal bones (Figure 2). On histopathological examination, there was acanthosis of the cells with signs of chronic inflammation. For laboratory workup, affected area was cleaned with 70% alcohol and pus sample was collected. White-colored granules were oozed out. The pus sample was processed for microbiological evaluation namely Gram’s staining, modified Ziehl Neelsen staining (using 1% acid decolorizer), and 10% potassium hydroxide (KOH) wet mount. Sample was directly inoculated on Sabouraud’s dextrose agar at 25°C and 37°C in the biochemical oxygen demand incubator. The sample was also directly inoculated on blood agar, Lowenstein Jensen media, and brain heart infusion broth (HiMedia Laboratories, Mumbai, India). 1
Dept. of Microbiology, IMS, Banaras Hindu University, Varanasi, India Dept. of Orthopaedics, IMS, Banaras Hindu University, Varanasi, India
2
Corresponding Author: Ragini Tilak, Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. Email: [email protected]
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Gupta et al
Figure-3. Hyaline fungal hyphae on potassium hydroxide (KOH) examination. Figure 1. Lower limb with multiple discharging sinuses.
Figure-4. Fungal hyphae on hematoxylin and eosin staining. Figure 2. X-ray image of lower limb showing involvement of tarsal and metatarsal bones.
On Gram’s staining, presence of pus cells was seen. No acid fast structure was seen. On 10% KOH wet mount, hyaline fungal hyphae were seen (Figure 3). The white-colored granules oozing out were 0.5 to 1 mm in size without any cement-like matrix. The granules were processed for Gram’s staining but failed to reveal any filamentous structure. On hematoxylin and eosin staining, fungal hyphae were observed (Figure 4). On Sabouraud’s dextrose agar, texture of the growth was cottony and moist initially, which became flat with fine, short, mycelial tufts later. On obverse view, color of the colony was light gray, which became dark gray to black as the colony matured. Reverse was gray to black at 25°C in the biochemical oxygen demand incubator.
Slide culture was done that revealed hyaline and septate hyphae on lactophenol mount. Conidogenous cells (annellides) were seen to arise directly from the hyphae. Conidia were unicellularly present at the apex of these annellides. A diagnosis of white grain mycetoma caused by S apiospermum was made. However, on the basis of KOH wet mount results and before the complete identification of the isolate, fluconazole (400 mg/d) was started empirically and the patient was advised to have follow-up after 15 days but failed to do so.
Discussion Eumycetoma is caused by filamentous fungi. Eumycetoma is classified according to the color—black or white—of the
Downloaded from ijl.sagepub.com at Scientific library of Moscow State University on January 16, 2014
288
The International Journal of Lower Extremity Wounds 12(4)
granules oozing out. Black grain mycetoma is quite common in south India in contrast to white grain mycetoma, which is common in north India. It usually affects the extremities, exposed parts like foot or hand. Chronic infection of the tissue leads to hard swollen mass with multiple discharging sinuses and oozing of granules. Superimposed bacterial infections also complicate the clinical outcome. In this report, we describe a case of white grain mycetoma caused by S apiospermum at a tertiary center in north India. Few cases of S apiospermum mycetoma have been reported from north India. Pseudoallescheria boydii is the teleomorphic stage of S apiospermum and a frequent cause of white grain mycetoma. This cosmopolitan fungus enters the tissues following penetrating injury. After subcutaneous inoculation of fungi, it proliferates and involves muscles and tissues underneath.4 Despite having gray-black-colored growth and brown-black conidia, the hyphae of S apiospermum are hyaline. Even Fontana-Masson staining is negative for melanin.5 Granules of S apiospermum are 1 to 2 mm, soft, irregular and white colored6 and surrounded by a eosinophilic fringe.7 Antifungal drugs, including amphotericin B, itraconazole, ketoconazole, and flucytosine have low in vitro efficacy against this fungus.8-14 However, voriconazole and ravuconazole are moderately effective.15 Amphotericin B and micafungin combination have synergistic effect against this fungus16 as micafungin, echinocandin, inhibit the (1,3)-β-d-glucan synthase, thus interfering with fungal cells.17,18 Amphotericin B becomes active in low dose once there is altered cell wall structure. Often a combination therapy of amphotericin B and micafungin is required for effective management of this highly resistant fungus and for its prompt identification. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Develoux M, Ndiaye B, Dieng MT. Mycetomas in Africa [in French]. Sante. 1995;5:211-217. 2. N’diaye B, Develoux M, Dieng MT, et al. Aspects actuels des mycétomes au Sénégal. A propos de 109 cas [in French]. J Mycol Méd. 2000;10:140-144. 3. Fahal AH. Mycetoma: a thorn in the flesh. Trans R Soc Med Hyg. 2004;98:3-11.
4. Grover CRN. Case presentation. Johns Hopkins Microbiol Newslett. 1997;16:13. 5. Kimura M, McGinnis MR. Fontana-Masson–stained tissue from culture-proven mycoses. Arch Pathol Lab Med. 1998;122:1107-1111. 6. Rippon JW. Medical Mycology. The Pathogenic Fungi and the Pathogenic Actinomycetes. 3rd ed. Philadelphia, PA: W.B. Saunders; 1998. 7. Hay RJ, Mackenzie DW. The histopathological features of pale grain eumycetoma. Trans R Soc Trop Med Hyg. 1982;76:839-844. 8. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother. 2001;45:2151-2153. 9. Cuenca-Estrella M, Ruiz-Díez B, Martínez-Suárez JV, Monzón A, Rodríguez-Tudela JL. Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. J Antimicrob Chemother. 1999;43:149-151. 10. Espinel-Ingroff A. In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J Clin Microbiol. 1998;36:198-202. 11. Meletiadis J, Meis JF, Mouton JW, Rodriquez-Tudela JL, Donnelly JP, Verweij PE; EUROFUNG Network. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob Agents Chemother. 2002;46:62-68. 12. Minassian B, Huczko E, Washo T, Bonner D, Fung-Tomc J. In vitro activity of ravuconazole against Zygomycetes, Scedosporium and Fusarium isolates. Clin Microbiol Infect. 2003;9:1250-1252. 13. Odabasi Z, Paetznick VL, Rodriguez JR, Chen E, OstroskyZeichner L. In vitro activity of anidulafungin against selected clinically important mold isolates. Antimicrob Agents Chemother. 2004;48:1912-1915. 14. Pfaller MA, Marco F, Messer SA, Jones RN. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis. 1998;30:251-255. 15. Radford SA, Johnson EM, Warnock DW. In vitro studies of activity of voriconazole (UK-109,496), a new triazole antifungal agent, against emerging and less-common mold pathogens. Antimicrob Agents Chemother. 1997;41:841-843. 16. Yustes C, Guarro J. In vitro synergistic interaction between amphotericin B and micafungin against Scedosporium spp. Antimicrob Agents Chemother. 2005;49:3498-3500. 17. Hatano K, Morishita Y, Nakai T, Ikeda F. Antifungal mechanism of FK463 against Candida albicans and Aspergillus fumigatus. J Antibiot (Tokyo). 2002;55:219-222. 18. Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362:1142-1151.
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