Joint Bone Spine 73 (2006) 321–324 http://france.elsevier.com/direct/BONSOI/

Case report

A rare European case of Madura Foot due to actinomycetes Luigi De Palma a,*, Mario Marinelli a, Matteo Pavan a, Ester Manso b, Renzo Ranaldi c a

Cattedra di Ortopedia e Traumatologia, Università Politecnica delle Marche, Ancona, Ospedali Riuniti Umberto 1°-Lancisi-Salesi, Via Conca, 60100 Ancona, Italy b Istituto di Microbiologia, Università Politecnica delle Marche, Ancona, Italy c Istituto di Anatomia Patologica, Università Politecnica delle Marche, Ancona, Italy Received 14 March 2005; accepted 4 October 2005

Abstract We present a case of mycetoma by Actinomadura spp. on the foot of an Albanian young man arrived to our observation approximately 5 years after the first clinical manifestations (hard tumefaction, slightly painful upon weight-bearing and palpation and cutaneous fistulas that discharged an abundant granulomatous secretion). Direct microscopic analysis and culture of the white-yellowish grains included Gram staining, which showed extensively branched Gram-positive hyphae less than 1 mm in diameter, allowing to make a diagnosis of Actinomycetoma. Since Actinomycetoma is sensitive to drug treatment, the patient was given trimethoprim-sulfamethoxazole and amikacin twice daily for 45 days. After six months of chemotherapy, the patient’s general condition improved, the swelling is slightly diminished and grain extrusion has ceased. The patient has been able to resume ambulation with normal footwear. Given the absence of liver and kidney functional alterations, the patient is scheduled to continue pharmacological treatment with trimethoprim-sulfamethoxazole. © 2006 Elsevier SAS. All rights reserved. Keywords: Actinomycetoma; mycetoma; fungal infection; maduromycosis; fungal mycetoma

1. Introduction Mycetoma is a chronic granulomatous infection of the skin and subcutaneous tissue caused by fungi (Eumycetoma) or bacteria (Actinomycetoma) that prevalently affects young people. It is mainly a disease of tropical and subtropical areas; in temperate regions true autochthonous cases have rarely been reported, of which no more than 17 in Europe [1,2]. The aim of this study is to investigate a case of Madura foot secondary to an Actinomycete infection in the Mediterranean region (Albania). 2. Case report A 45-year-old Albanian man came to our observation approximately 5 years after the first clinical manifestations of an infection of probable mycotic origin that had progressively spread to involve the whole posterior right foot following a * Corresponding

author. Tel.: ++39-071-5963349, fax: ++39-071-5963349. E-mail address: [email protected] (L. De Palma).

1297-319X/$ - see front matter © 2006 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.10.018

minor traumatic cutaneous lesion to the foot’s dorsum. A hard tumefaction, slightly painful upon weight bearing and palpation, developed at the site of the lesion, as did cutaneous fistulas that discharged an abundant granulomatous secretion (Fig. 1). The extension of the swollen area prevented ambulation with normal footwear. The patient reported being treated unsuccessfully with antibiotics he could not name. When he came to our observation, the dorsomedial surface of the hindfoot exhibited a painful swelling the size of an orange, of woody induration, that was anchored both to deep and superficial planes. The overlying skin was slightly reddened and warm to the touch. Sinus tracts discharging pus containing white-yellowish grains were also present (Fig. 1). Numerous small scars were the outcomes of previous fistulas. Biochemical tests evidenced slightly increased ESR (40 mm/h). Conventional X-rays at the time of the first clinical examination revealed soft tissue involvement of the dorsal aspect of the foot (Fig. 2). MRI shows a diffused low signal in the mid tarsal bones (navicular and cuneiform bones), at the talus and tibia, and evidenced massive soft tissue infiltration and lesions of high signal intensity immersed in a low-intensity matrix in the whole hindfoot (Fig. 3A,B).

322

L. De Palma et al. / Joint Bone Spine 73 (2006) 321–324

Fig. 1. Mildly painful swelling in the dorso-medial region of middle and hindfoot.Cutaneous fistula secreting purulent material containing whiteyellowish granules.

Fig. 2. Latero-lateral X-ray projection of right foot. Soft tissue involvement of the dorsal aspect of the foot.

Direct microscopic analysis and culture of the white-yellowish grains included Gram staining, which showed extensively branched Gram-positive hyphae less than 1 mm in diameter, allowing to make a diagnosis of Actinomycetoma. The grains were placed onto plates containing Columbia Agar and 5% sheep blood and incubated under aerobic and anaerobic conditions at 35 °C, and in Sabouraud glucose agar medium containing 0.05 mg/ml chloramphenicol at 30 °C. Within 10 days, very small colonies, adherent, smooth, rough, rose coral or peach-coloured were isolated from the Columbia blood agar plates cultured under aerobic conditions. Stereomicroscopy showed dividing septa whose number increased with further incubation (Fig. 4). The isolate was not acid-fast upon modified Ziehl-Neelsen staining. Biochemical analysis indicated sensitivity of the isolate to lysozyme, decomposition of casein, and failure to digest xanthine and tyrosine and to hydrolyze

Fig. 3. A:.Sagittal MRI T1 TR (600) TE (14) scan of right foot showing a diffuse low signal in the mid tarsal bones, at the talus and tibia. B:.Sagittal MRI T2 TR (4500) TE (96) scan of right foot showing massive soft tissue infiltration and high-intensity lesions dispersed in a low-signal intensity fibrous matrix.

urea. The strain was identified as Actinomadura spp. [3,4]. Antimicrobial susceptibility tests with E-test strips (AB-Biodisk, Solna, Sweeden) on Mueller-Hinton agar and 5% horse blood yielded amikacin, trimethoprim-sulfamethoxazole and imipenem MICs of 0.75, 32 and > 4 μg/ml, respectively. Histopathological examination of a skin fragment collected above the tumefaction exhibited non-specific lesions: dense fibrosis of the papillary and reticular derma, medial-intimal thickening of vascular walls and a mild chronic inflammatory infiltrate (Fig. 5). The etiological agent could not be identified in this specimen. Since Actinomycetoma is sensitive to drug treatment [5], the patient was given 960 mg trimethoprim-sul-

L. De Palma et al. / Joint Bone Spine 73 (2006) 321–324

323

3. Discussion

Fig. 4. Stereomicroscopic image of colonies exhibiting dividing septa whose number increased with increasing time into culture.

Fig. 5. Papillary and reticular dermal fibrosis with mild, chronic inflammatory infiltrate. Hematoxylin-Eosin, 40x.

famethoxazole and 15 mg/kg amikacin i.m. twice daily for 45 days; then, only 960 mg trimethoprim-sulfamethoxazole i. m. daily for 6 months. Because of the diffused soft tissue infiltration, we opted against conservative surgical treatment (debridement or local resection). Amputation was not considered. Biochemical tests and clinical examination were performed at 15 days’ intervals to monitor liver and kidney function. After six months of chemotherapy, the patient’s general condition improved, the swelling has slightly diminished and grain extrusion has ceased. The patient has been able to resume ambulation with normal footwear. Given the absence of liver and kidney functional alterations, the patient is scheduled to continue pharmacological treatment with trimethoprim-sulfamethoxazole.

Madura foot (Mycetoma) is a chronic infection of the skin, subcutaneous tissue, muscles and, occasionally, underlying bone [6] caused by fungi (Eumycetoma) or bacteria (Actinomycetoma) [7,8]. Initially named after the Indian region where it was first identified, this condition is most common in tropical and subtropical regions and in areas where annual rainfall is low (where people often walk barefoot), even though cases have also occurred in other geographical areas. Madura foot typically affects male agricultural workers aged between 20 and 50, often secondary to a minor trauma [8–10]. The most common site of infection is the foot, followed by the hand; shin and knee are seldom affected. Rare forms of primary bony infection without previous or associated skin manifestations have also been reported. Such forms, due to direct inoculation of the fungus through penetrating wounds [11], are infrequent and have been described in the rotula and the anteromedial diaphysis of the tibia and tibial malleolus [11–13]. Tibial and rotulean localizations can be explained with the absence of muscles covering the bone [14]. More than 20 species of fungi and bacteria have been implicated as etiologic agents of Mycetoma. Approximately 40% of the cases are due to true fungi (Eumycetoma: Madurella mycetomatis and Pseudallescheria boydii); in the other 60%, the infection is supported by actinomycetes (Actinomycetoma) [15,16] , whose most frequent causative agents are Nocardia brasiliensis, Actinomadura (Streptomyces) pelletieri, Streptomyces somaliensis, Actinomadura madurae and Madurella mycetomatis [10]. The infection runs a relentless course over many years. The characteristic triad of symptoms consists of a painless indurated swelling that slowly extends to infiltrate surrounding and underlying soft tissues, multiple, intermittently draining sinus tracts, and presence of granules in their purulent discharge. Formation of fistulae is a reliable indicator of disease duration: they are rarely found before 3 months from the onset of clinical symptoms, one third of patients exhibit them between 3 and 6 months, and nearly all have them at 1 year [17]. The bony involvement is widely considered a late event that does not affect prognosis. Neither systemic symptoms nor distant metastases are known. X-rays and MRI are helpful to confirm the diagnosis and determine the extension of the pathological process and stage of the disease. Regarding the latter aspect, the 7-stage system proposed by Abd El Bagi [18], to classify the radiographic pattern and the extent and severity of bone involvement in Mycetoma, is particularly interesting: stage 0 indicates the presence of soft-tissue swelling without bone involvement; stage I, the pressure exerted on the intact bone in the vicinity of an expanding granuloma; stage II, the irritation of the bone surface without actual intraosseous invasion. Cortical erosion and central cavitation occur in stage III. If the disease spreads longitudinally along a single ray, stage IV is established. Horizontal spread with invasion of adjacent structures that involve more than one ray but is limited to one or two contiguous rows of small bones represents stage V. Multidirectional spread due to uncontrolled infection is classified as stage VI. Small granulomas are also

324

L. De Palma et al. / Joint Bone Spine 73 (2006) 321–324

well imaged on MRI scans, appearing as areas of high signal intensity interspersed within a low-intensity matrix. According to Abd El Bagi [18], the low-signal matrix represents fibrous tissue and the central high-signal focus the characteristic organized fungal elements (grains) found in this condition. Biopsy and microscopic examination of the grainy secretions are required for diagnosis and for identifying the most suitable therapy [7]. Treatment is conditioned by the stage of the disease which is frequently advanced at the time of diagnosis. Actinomycetoma is considered sensitive to associations of drugs like trimethoprim-sulfamethoxazole and amikacin, penicillins, and tetracyclines. Surgical intervention becomes necessary when Mycetoma does not respond to chemotherapy [9]. The choice among debridement, local excision, and amputation depends on the extent of the lesion and of soft tissue infiltration. 4. Conclusions Mycetoma is a rare chronic infection of the cutis and subcutis. Actinomycete is the most frequently involved causative agent. The pathological process is slow and long asymptomatic. The usually advanced disease stage at the time of diagnosis influences the treatment and outcome. Successful pharmacological treatment of our patient confirmed that Actinomycetoma is sensitive to antibiotic therapy. References [1]

Carrasco C, Leite S, Sobral C, et al. Osegundo e terceiro casos portuguesses autoctones de micetoma. Bol Clin Hosp Civis Lisb 1959;20: 231–5.

[2] Degavre B, Joujoux JM, Dandurand M, Guillot B. First report of mycetoma caused by Arthrographis kalrae: successful treatment with itraconazole. J Am Acad Dermatol 1997;37:318–20. [3] Kwon KJ, Chung, Bennett JE. USA: Medical mycology. Williams and Wilkins Ed. Media; 1992. [4] Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH. Manual of clinical Microbiology 8th Ed. Washington, USA: ASM Press; 2003. [5] Foltz KD, Fallat LM. Madura foot: atypical finding and case presentation. J Foot Ankle Surg 2004;43:327–31. [6] Nikolaos K. Painless foot swelling with a chronic purulent discharge. West J Med 2001;174:96–7. [7] Miller SD. Madura foot: treatment of Nocardia nova infection with antibiotics alone. Am J Orthop 2001;30:495–8. [8] Khatri ML, Al-Halali HM, Fouad Khalid M, Saif SA, Vyas MC. Mycetoma in Yemen: clinicoepidemiologic and histopathologic study. Int J Dermatol 2002;41:586–93. [9] Welsh O, Salinas MC, Rodriguez MA. Treatment of eumycetoma and actinomycetoma. Curr Top Med Mycol 1995;6:47–71. [10] Gorbach SL, Barlett JG, Blacklow NR. In: Infectious diseases. 2nd ed. Philadelphia; 1998. p. 2376–81. [11] Saxena PS, Udawat MP, Singh H. Unusual manifestations of mycetoma. Trop Geogr Med 1979;31:253–6. [12] Majid MA, Mathias PF, Seth HN, Thirumalachar MJ. Primary mycetoma of the patella. J Bone Joint Surg Am 1964;46:1283–6. [13] Burkus JK. Primary mycetoma infection of the distal tibia secondary to an occult foreign body. Foot Ankle 1985;6:47–52. [14] Rippon JW, Carmichael JW. Petriellidiosis (Allescheriosis): four unusual cases and review of literature. Mycopathologia 1976;58:117–24. [15] Saag MS, Goldman L, Bennet JC. In: Cecil textbook of Medicine, 21st Ed. Philadelphia: USA; 2000. p. 1885–7. [16] Yera H, Bougnoux ME, Jeanrot C, Baixench MT, De Pinieux G, Dupouy-Camet J. Mycetoma of the foot caused by Fusarium solani: identification of the etiologic agent by DNA sequencing. J Clin Microbiol 2003;41:1805–8. [17] McGinnis MR, Fader RC. Mycetoma: a contemporary concept. Infect Dis Clin North Am 1988;2:939–54. [18] Abd El Bagi ME. New radiographic classification of bone involvement in pedal mycetoma. AJR Am J Roentgenol 2003;180:665–8.

ID 3367310

Title A rare European case of Madura Foot due to actinomycetes

http://fulltext.study/journal/3057

http://FullText.Study

Pages 4