Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulosimicrobium cellulans and who received treatment with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).info:eu-repo/semantics/publishedVersio

Maltez, F

Sousa Nunes, B

Trindade Torres, M

Varandas, L

Acta Médica Portuguesa

English

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulosimicrobium cellulans and who received treatment with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).publishersversionpublishe

Trindade Torres, Margarida

Sousa Nunes, Beatriz

Varandas, Luís

Maltez, Fernando

Repositório da Universidade Nova de Lisboa

PERSPECTIVA46Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.comIMAGENS MÉDICASARTIGO DE REVISÃOCASO CLÍNICOCARTASNORMAS ORIENTAÇÃOARTIGO ORIGINALEDITORIALABSTRACTMycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulo-simicrobium cellulans and treated with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).Keywords: Actinomycetales; Mycetoma/diagnosis; Mycetoma/therapyRESUMOO micetoma é causado pela inoculação subcutânea de fungos filamentosos ou bactérias filamentosas aeróbias. Cellulosimicrobium cellulans é uma bactéria Gram positivo da ordem Actinomycetales, que raramente causa doença em humanos. O diagnóstico é baseado na apresentação clínica e na identificação do microrganismo. Apresentamos uma breve revisão de literatura, a propósito do caso clínico de um jovem com diagnóstico de actinomice-toma por Cellulosimicrobium cellulans tratado com uma associação de amicacina e sulfametoxazol/trimetoprim (esquema de Welsh). Palavras-chave: Actinomycetales; Micetoma/diagnóstico; Micetoma/tratamentoActinomycetoma by Cellulosimicrobium cellulans in a Young Man from Guinea- -Bissau: Short Literature Review Regarding a Case ReportActinomicetoma por Cellulosimicrobium cellulans num Jovem Guineense: Breve Revisão de Literatura a Propósito de um Caso ClínicoMargarida TRINDADE TORRES1, Beatriz SOUSA NUNES2, Luís VARANDAS2,3,4, Fernando MALTEZ1Acta Med Port 2024 Jan;37(1):46-50  ▪  https://doi.org/10.20344/amp.17356INTRODUCTION Mycetoma is a chronic, localized and slowly progressive disease of the skin and soft tissue, caused by ubiquitous bacteria (actinomycetoma) and fungi (eumycetoma).1 It is endemic in tropical and subtropical areas. The treatment depends on the etiology and other factors, and the cure rate is variable.2–4 Cellulosimicrobium cellulans (C. cellulans) is a Gram-positive bacteria that rarely causes human dis-ease.5,6 We present the case of a young man from Guinea-Bis-sau diagnosed with actinomycetoma due to C. cellulans. The indolent clinical course and complications, related to the delayed diagnosis and multiple therapeutic regimens, underline the importance of its recognition in non-endemic countries.CLINICAL REPORT In 2017, a 17-year-old male from Guinea-Bissau was transferred under an agreement between the governments of Portugal and Guinea-Bissau to a Paediatric Infectious Diseases department in Portugal, for the investigation of intermittent fever and nodular exudative lesions of the left foot that had been evolving for six years. With no history of trauma, he initially had a painless nodule on the plantar as-pect of the foot that gradually developed purulent discharge and a firm swelling. On physical examination, he had multiple infiltrative nod-ules and sinuses, with purulent and haemorrhagic drainage, and oedema reaching the ankle and leading to important functional limitations (Fig. 1). The Laboratory tests revealed a normal blood cell count, elevation of C-reactive protein (52.7 mg/L) and erythrocyte sedimentation rate (44 mm/h). The interferon-gamma release assay (IGRA) was negative and the chest X-ray was unremarkable. A magnetic reso-nance imaging (MRI) of the left foot revealed a granuloma-tous mass with extensive local involvement of the subcu-taneous tissue, muscles, and bones, with multiple nodular lesions showing the ‘dot-in-circle’ sign and several foci of avascular necrosis of the bone (Fig. 2). The histologic examination of a tissue biopsy identified spore aggregates with periodic acid-reactive Schiff (PAS) stain. Admitting the diagnosis of eumycetoma, he was start-ed on itraconazole. Due to lack of clinical improvement, a second biopsy was performed. The histological examination showed a “granu-lomatous inflammatory infiltrate and basophilic filamen-tous microorganisms suggestive of Actinomyces” and the pan-bacterial polymerase chain reaction (PCR) identified C. cellulans, thus supporting the diagnosis of actinomycetoma.1. Serviço de Doenças Infeciosas. Hospital de Curry Cabral. Lisboa. Portugal.2. Serviço de Infeciologia Pediátrica. Hospital de Dona Estefânia. Lisboa. Portugal.3. NOVA Medical School. Faculdade de Ciências Médicas. Lisboa. Portugal.4. Instituto de Higiene e Medicina Tropical. Lisboa. Portugal. Autor correspondente: Margarida Trindade Torres. margarida.torres@chlc.min-saude.ptRecebido/Received: 21/10/2021 - Aceite/Accepted: 09/11/2022 - Publicado Online/Published Online: 15/03/2023 - Publicado/Published: 03/01/2024Copyright © Ordem dos Médicos 2024PERSPECTIVAwww.actamedicaportuguesa.comIMAGENS MÉDICASARTIGO DE REVISÃOCASO CLÍNICOCARTASNORMAS ORIENTAÇÃOARTIGO ORIGINALEDITORIAL47Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.comTrindade Torres M, et al. Actinomycetoma by Cellulosimicrobium cellulans, Acta Med Port 2024 Jan;37(1):46-50 In the following months, the patient received sequen-tial treatment with β-lactams, aminoglycosides and sulfa-methoxazole/trimethoprim (STX/TMP) in monotherapy and underwent several surgical debridements, without improve-ment of the nodules and oedema.  In 2018, he received treatment with continuous oral STX/TMP in association with a four-week course of me-ropenem every two weeks, complemented by debridements and hyperbaric oxygen treatments. In April 2019, the patient was transferred to the adult ID Department, with nine cycles of this regimen completed, showing regression of the oedema, but still with recurrence of the subcutaneous nodular lesions between meropenem courses. He was reassessed with an MRI, which, despite showing some improvement, identified multiple bone and subcutaneous lesions. After a review of the literature, he was started on four courses of amikacin 15 mg/kg/day for three weeks and con- Figure 1 – Actinomycetoma of the left foot: multiple nodular lesions with sinuses and severe deformitytinuous oral STX/TMP 35 mg/kg/day, with two-week amika-cin free periods. The patient completed treatment, without relapse of the lesions after the second course of amikacin, and with full functional recovery. No otologic or renal toxicity occurred. For the next 15 months, he was evaluated every three months, without recurrence of lesions on physical exami-nation. In January 2021, the magnetic resonance imaging (MRI) showed significant decrease in the number of lesions, no new nodules and stable bone involvement (Fig. 3).DISCUSSION The first case of mycetoma was described by Dr John Gill, in the Indian town of Madura, in 1842, referring to the disease as Madura foot.7,8 Since 2016, it is among the ne-glected tropical diseases according to the World Health Or-ganization.9 Most cases occur in the ‘Mycetoma Belt’, which includes tropical and subtropical areas of Africa, Central and South America and Asia, particularly the Indian subcontinent. The true incidence and prevalence are unknown.2,9–11 Some studies demonstrate a higher prevalence in men, while oth-ers show no difference between sexes.1,10,12,13 It is a chronic, localized and slowly progressive disease and most frequently affects feet and hands. It is character-ized by painless subcutaneous granulomas, with sinuses draining pus, blood and grains, which results in destruction of structures and deformity.2,4,7,14–16 Bone involvement may occur.4,12,13,16,17 Mycetoma is caused by ubiquitous fungi (eumycetoma) or filamentous bacteria (actinomycetoma), found in soil and plants of endemic countries, with more than 50 species identified.2,3,12,14,15 It is most frequently caused by Nocar-dia, Streptomyces, and Actinomadura.2,4,11,17 The disease evolves within weeks to years after skin trauma.15–17 The diagnosis is based on physical findings, biopsy or fine needle aspiration, and imaging. The identification of mi-croorganisms can be made by histopathologic examination, culture and molecular techniques, and involvement of struc-tures can be evaluated using radiography, ultrasonography, computed tomography scan, and MRI, with the last being more sensitive.2,18 The ‘dot-in-circle’ sign, in ultrasound or MRI, is considered pathognomonic of musculoskeletal my-cetoma.18,19 The differential diagnosis includes sporotrichosis, tu-berculosis, osteomyelitis, coccidiomycosis, botryomycosis, other fungal infections, and neoplasms of the bone and soft tissues.4,11 The treatment choice depends on the causative agent, disease extension, and host factors. The combination of STX/TMP and amikacin, with or without rifampicin (Welsh regimen and modified Welsh regimen) showed good PERSPECTIVA48Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.comIMAGENS MÉDICASARTIGO DE REVISÃOCASO CLÍNICOCARTASNORMAS ORIENTAÇÃOARTIGO ORIGINALEDITORIALRevista Científica da Ordem dos MédicosTrindade Torres M, et al. Actinomycetoma by Cellulosimicrobium cellulans, Acta Med Port 2024 Jan;37(1):46-50 Figure 2 – MRI revealing nodular lesions, with ‘dot-in-circle’ sign (arrows), involving bone, muscles and subcutaneous tissue of the left footA B Figure 3 – Post-treatment MRI of the left foot showing regression of the lesions and tissue edema, with bone sequelaeA BPERSPECTIVAwww.actamedicaportuguesa.comIMAGENS MÉDICASARTIGO DE REVISÃOCASO CLÍNICOCARTASNORMAS ORIENTAÇÃOARTIGO ORIGINALEDITORIAL49Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.comTrindade Torres M, et al. Actinomycetoma by Cellulosimicrobium cellulans, Acta Med Port 2024 Jan;37(1):46-50 Trindade Torres M, et al. Actinomycetoma by Cellulosimicrobium cellulans, Acta Med Port 2024 Jan;37(1):46-50outcomes.11,13,16 The alternatives are STX/TMP and dap-sone or rifampicin; amoxicillin/clavulanate and netilmicin, for STX/TMP and amikacin allergy, respectively; amikacin and meropenem or imipenem can be used in refractory cas-es; other combinations can be used as well.4,12,13,15–17 The guidelines from the Mycetoma Research Centre of Khar-toum recommend streptomycin and dapsone as first-line drugs.20 Monotherapy is not recommended.2,13,15,16 Surgical treatment is indicated for localized lesions and for large lesions, in combination with antibiotics, to reduce the organism load.17 C. cellulans, formerly known as Oerskovia xanthineolyt-ica and Nocardia cellulans, is a gram-positive bacillus from the order Actinomycetales, and is distributed widely in the environment. It is a rare human pathogen.5,6 In a literature review published in 2019, the main risk factors for C. cellulans infection were underlying chronic disease affecting the immune system and the presence of foreign bodies. Only one case of abscess formation related with intramuscular injections has been described. The iso-lates were susceptible to vancomycin, STX/TMP, imipenem and amikacin.6 The literature provides a good, albeit fragmented, over-view of the presentation and etiology of mycetoma. How-ever, there are no randomized controlled trials on the best therapeutic approach, leading clinicians to make decisions based on case reports, small retrospective studies, and scarce systematic reviews.  This case report describes a delayed and complex di-agnosis of actinomycetoma, which happen often outside reference centres. Therefore, it emphasizes the importance of early recognition of the disease and identification of the causative microorganism. Several factors may have contributed to the ineffective-ness of the previous therapeutic regimens, such as lesion extension, difficult identification of the microorganism and no antibiotic susceptibility testing, monotherapy regimen, and short courses of treatment. The decision on the best therapeutic approach was also challenging due to lack of guidelines for the treatment of mycetoma in our setting and no information on the suscep-tibility profile of C. cellulans.AUTHORS CONTRIBUTION All authors contributed equally to this manuscript.PROTECTION OF HUMANS AND ANIMALS The authors declare that the procedures were followed according to the regulations established by the Clinical Re-search and Ethics Committee and to the Helsinki Declara-tion of the World Medical Association updated in 2013.PATIENT CONSENT  Obtained.COMPETING INTERESTS The authors have declared that no competing interests exist.FUNDING SOURCES This research received no specific grant from any fund-ing agency in the public, commercial, or not-for-profit sec-tors.REFERENCES1. Emery D, Denning DW. The global distribution of actinomycetoma and eumycetoma. PLoS Negl Trop Dis. 2020;14:1-13.2. Zijlstra EE, van de Sande WW, Welsh O, Mahgoub ES, Goodfellow M, Fahal AH. Mycetoma: a unique neglected tropical disease. Lancet Infect Dis. 2016;16:100-12.3. van de Sande WW. Global burden of human mycetoma: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2013;7:1-11.4. Emmanuel P, Dumre SP, John S, Karbwang J, Hirayama K. Mycetoma: a clinical dilemma in resource limited settings. Ann Clin Microbiol Antimicrob. 2018;17:1-10.5. Fatahi-bafghi M. Nocardiosis from 1888 to 2017. Microb Pathog. 2017;114:169-84.6. Rivero M, Alonso J, Ramón MF, Gonzalez N, Pozo A, Marín I, et al. Infections due to cellulosimicrobium species: case report and literature review. BMC Infect Dis. 2019;19:1-9.7. Duane RH. Agents of mycetoma. In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 9th ed. Philadelphia: Elsevier; 2020. p.3141-5.e1.8. Ramachandra BV, Nayar AS, Subhashini, Chennamsetty K. Mycetoma caused by madurella mycetomatis. Lancet Infect Dis. 2013;2:305. 9. World Health Organization. Results of the 2017 global WHO survey on yaws. Wkly Epidemiol Rec. 2017;93:417-22.10. Fahal A, Mahgoub ES, Mohamed A, Abdel-Rahman ME, Alshambaty Y, Hashim A, et al. A new model for management of mycetoma in the Sudan. PLoS Negl Trop Dis. 2014;8:1-12.11. Welsh O, Vera-Cabrera L, Welsh E, Salinas MC. Actinomycetoma and advances in its treatment. Clin Dermatol. 2012;30:372-81.12. Arenas R, Fernandez Martinez RF, Torres-Guerrero E, Garcia C. Actinomycetoma: an update on diagnosis and treatment. Cutis. 2017;99:E11-5.13. Garza JA, Welsh O, Cuéllar-Barboza A, Suarez-Sánchez K, de la Cruz-Valadez E, Cruz-Gomez L, et al. Clinical characteristics and treatment of actinomycetoma in northeast Mexico: a case series. PLoS Negl Trop Dis. 2020;14:1-14.14. Hay RJ. Subcutaneous mycoses: general principles. In: Ryan ET, Hill DR, Solomon T, Aronson NE, Endy TP, editors. Hunter’s Tropical Medicine and emerging infectious disease. 10th ed. Philadelphia: Elsevier; 2020. p.653-8.15. Salim AO, Mwita CC, Gwer S. Treatment of madura foot: a systematic review. JBI Database Syst Rev Implement Rep. 2018;16:1519-36.16. Agarwal P, Jagati A, Rathod SP, Kalra K, Patel S, Chaudhari M. Clinical features of mycetoma and the appropriate treatment options. Res Rep Trop Med. 2021;12:173-9.17. Verma P, Jha A. Mycetoma: reviewing a neglected disease. Clin Exp Dermatol. 2019;44:123-9.18. Shamy ME, Fahal AH, Shakir MY, Homeida MM. New MRI grading system for the diagnosis and management of mycetoma. Trans R Soc Trop Med Hyg. 2012;106:738-42.PERSPECTIVA50Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.comIMAGENS MÉDICASARTIGO DE REVISÃOCASO CLÍNICOCARTASNORMAS ORIENTAÇÃOARTIGO ORIGINALEDITORIALTrindade Torres M, et al. Actinomycetoma by Cellulosimicrobium cellulans, Acta Med Port 2024 Jan;37(1):46-5019. Laohawiriyakamol T, Tanutit P, Kanjanapradit K, Hongsakul K, Ehara S. The “dot-in-circle” sign in musculoskeletal mycetoma on magnetic resonance imaging and ultrasonography. Springerplus. 2014;3:1-7.20. Fahal AH. Evidence-based guidelines for the management of mycetoma patients. Mycetoma Research Center. Khartoum: University of Khartoum; 2002.

Short Literature Review Regarding a Case Report

Repositório da Unidade Local de Saúde São José

Actinomicetoma por Cellulosimicrobium cellulans num Jovem Guineense: Breve Revisão de Literatura a Propósito de um Caso Clínico

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulosimicrobium cellulans and who received treatment with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).</jats:p

Margarida Trindade Torres

Beatriz Sousa Nunes

Luís Varandas

Fernando Maltez

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Actinomycetoma by Cellulosimicrobium cellulans in a Young Man from Guinea-Bissau: Short Literature Review Regarding a Case Report

Actinomicetoma por Cellulosimicrobium cellulans num Jovem Guineense: Breve Revisão de Literatura a Propósito de um Caso Clínico

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Repositório da Universidade Nova de Lisboa

Repositório da Unidade Local de Saúde São José

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