Tools
Eumycetoma
Introduction
Mycetoma is a progressive chronic granulomatous infection that affects the skin and subcutaneous tissue.[1] Mycetoma can be classified as "eumycetoma" when it is caused by fungi or "actinomycetoma" when caused by bacteria in the order Actinomycetes. Eumycetoma is, therefore, a deep fungal infection of the skin and subcutaneous tissue caused by filamentous fungi.[2] Morphologically and histologically, eumycetoma is characterized by a deep fungal infection that induces deep granulomatous inflammation and results in the formation of grains, which destroys deep tissues, muscles, bones, joints, and tendons.[3][4][5]
The World Health Organization (WHO) recognizes mycetoma as a neglected tropical disease with a significant disease burden, which primarily affects individuals in tropical and subtropical regions who come into direct contact with soil. The foot is particularly the most common site of fungal infections, as it frequently comes into contact with fungi in the soil through skin trauma due to the natural exposure of soil-borne fungi that breach the skin.[6][7] In less frequent instances, other areas, such as the legs or hands, may also be affected, as these infections usually enter through skin damage and, in rare cases, spread via hematogenous dissemination to other sites.[8][9][10]
The most common filamentous fungi causing an eumycetoma is Madurella mycetomatis.[11] These organisms are found in the soil and implanted in the skin after minor trauma.[12] Slow progressive subcutaneous swelling develops, followed by the formation of multiple nodules that evolve into suppurative lesions with numerous draining sinus tracts, from which colonies of causative organisms are discharged.[13] Managing eumycetoma poses significant challenges and necessitates a prolonged treatment regimen that often combines systemic antifungal therapy for an extended duration (6 months or more) with surgical interventions.[14] Neglected infections may lead to severe tissue destruction, underscoring the medical significance and treatment complexities associated with eumycetoma.[15][16] In endemic areas, eumycetomas lead to socio-economic consequences involving affected patients and their families.
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The most prevalent causative agent of eumycetoma worldwide is M mycetomatis. Etiologic agents of eumycetoma can be classified based on the type of grain they produce, typically categorized as black, white or pale unstained, or yellow-to-yellow-brown grains. Some of the important causes of the disease are mentioned below.
- Dark and black grains: Dark and black grains are primarily associated with pathogens such as M mycetomatis, Trematosphaeria grisea (formerly M grisea), Exophiala jeanselmei, Medicopsis romeroi (formerly Pyrenochaeta romeroi), Falciformispora senegalensis (formerly Leptosphaeria senegalensis), F thompkinsii, and Curvularia lunata.
- White or pale unstained grains: White or pale unstained grains are commonly associated with pathogens such as Acremonium spp, Fusarium spp, Neotestudina rosatii, Aspergillus nidulans, and A flavus, as well as Microsporum ferrugineum, M audouinii, and M langeronii. In addition, Scedosporium apiospermum and S boydii (formerly Pseudallescheria boydii) are also linked to this type of grain.
- Yellow-brown grains: Yellow-brown grains are typically attributed to pathogens such as Nocardia brasiliensis, N otitidiscaviarum (formerly N caviae), Actinomadura madurae, and Streptomyces somaliensis.
- Yellow grains: Yellow grains can be associated with Pleurostomophora ochrac.[17]
Many of these organisms are endemic to tropical areas; however, cases are also reported in the United States and other countries.[1]
Epidemiology
Mycetoma was included in the WHO list of neglected tropical diseases in 2016. Populations in tropical and subtropical countries, such as India, and West African countries, such as Senegal and Sierra Leone, who often walk barefoot, are particularly affected.[18] The regions where mycetomas are endemic are commonly referred to as the "Trans-African Belt" or "mycetoma belt." This belt extends between 15° and 30° north latitude, covering geographical areas from Sudan to Senegal.[17] Primary mycetomas are rare in developed nations and typically observed in individuals migrating from endemic countries.
Eumycetomas are predominantly observed in adult men at a ratio of 4:1 or higher, likely due to the mode of disease transmission.[19] Individuals with increased exposure to soil and a history of prior trauma to their feet or other soil-exposed areas, including farmers, homemakers, and breeders, are at higher risk of developing this condition. However, only 20% of individuals recalled experiencing a preceding traumatic event, typically involving injuries caused by splinters, thorns, or other activities related to animal bites or physical exertion.[20]
Pathophysiology
Classically, the disease course begins with fungi entering through broken skin, which are naturally found in soil, water, or plants.[21] These organisms then start to form a clonal population, leading to the development of grains.[22] Subsequently, their pathogenicity is likely based on their ability to evade the host immune system and induce changes in the host response. Interleukins (IL), such as IL-35 and IL-37, are associated with the lesion size of eumycetoma, playing a role in dampening the immune system. These ILs are negatively correlated with the levels of IL-1β and IL-12 in eumycetoma infection, thereby impacting disease progression.[23]
Low levels of interferon-γ and increased IL-10 have also been associated with harmful disease progression. Fungal elements, such as melanin and carotene, along with the ability of yeast to survive after a host neutrophilic and macrophage response, are likely involved in shielding the organism from complete degradation and subsequent granuloma formation.[24]
Histopathology
Key histopathological features of eumycetoma include the formation of epithelioid granulomas containing microcolonies and grains,[2] which are conglomerates of fungal hyphae. A foreign body reaction to fungal elements in eumycetomas leads to granuloma formation characterized by epithelioid cell hyperplasia and multinucleated giant cells.[25] Histological examinations of eumycetomas typically involve hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. Additionally, a methenamine silver stain may be considered.[26] This microscopic image provides a detailed view of Aspergillus niger, showcasing its characteristic features such as wide, branching septate hyphae and well-formed conidial heads (see Image. Histopathological View of Aspergillus niger).[17]
History and Physical
Eumycetoma primarily manifests on the feet (followed by hands and legs) and presents as painless plaques with hard woody swelling, discharging sinuses, and characteristic granular grains or microcolonies, representing key clinical features.[20] Communicating sinuses and fistulae actively discharge purulent material and granules, varying in color from white to yellow to black. Scarring and hyperpigmentation are commonly observed in the surrounding skin. Eumycetomas are endemic among barefoot-walking populations in Africa and Southeast Asia.[17] Therefore, the classic triad of eumycetoma includes tumor growth, sinus tracts, and discharge with grains.[27] Following inoculation of the causative agent, subcutaneous mycosis gradually develops over months to years, indicating a chronic infection.[28]
Evaluation
Clinical evaluation may be sufficient for diagnosis, especially in low-resource settings, based on the triad of diagnostic findings (tumor, sinus tracts, and discharge with grains). However, additional testing may be necessary, including culture, which can take up to 2 months, ultrasonography, or fine needle aspiration, which is the preferred method.[20][29] Advanced imaging studies may not be readily available, as this condition often presents in low-resource settings.
Punch Biopsy and Histopathological Examination of Skin Tissue
The most specific test for diagnosing eumycetoma involves examining grains or granules from discharge, both visually and microscopically.[30] This examination can be conducted on spontaneously drained material or material manually expressed from the sinus, although there is a risk of sample contamination with expressed material.[2] In many cases, a punch biopsy may not be necessary. However, a deep punch biopsy can be a diagnostic tool if drainage material cannot be expressed or examined. Grains or microcolonies are typically found in the subcutaneous tissue, necessitating a deep punch or excisional biopsy to access the morphological structures of eumycetomas. H&E staining of tissue sections and fungal staining techniques such as PAS provides detailed visualization of fungal grains.[31]
Imaging and Additional Diagnostic Modalities
The effective treatment of eumycetoma hinges upon accurately identifying the causative agent and assessing the extent of the disease. Imaging may be necessary to determine the disease burden, utilizing techniques such as x-ray, ultrasonography, computed tomography (CT) scans, and magnetic resonance imaging (MRI).[32] CT scans are particularly advantageous over traditional radiography. MRI may be employed when there are concerns regarding soft tissue or bone involvement, with a characteristic finding known as the "dot-in-circle" sign.[33][34][35] Surgical biopsy, histopathological examination, and fungal tissue cultures are crucial in identifying the organism. Additionally, molecular techniques such as species-specific polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and counter immunoelectrophoresis may be utilized for further characterization.
Treatment / Management
The treatment of eumycetoma remains challenging, as no definitive treatment protocol guidelines have been established. Current treatment strategies are primarily derived from published case reports and case series. Typically, treatment involves a combination of antifungal therapies and surgical procedures. Initially, preoperative antifungal therapy is administered for a duration of 6 months, followed by surgical procedures aimed at debulking and reducing the disease burden, succeeded by an additional 6 months of antifungal therapy.[36] However, some reported cases have shown improvement with medical therapy alone.[37][38][39] Notably, in many low-resource settings, medical treatment may be the only feasible option, as surgical debridement may not be readily available.(B3)
Antifungal Therapy
Various classes of antifungals have been used to treat eumycetoma, including azoles, amphotericin B, and terbinafine.
Azoles: Azole antifungals are considered the "gold standard" for treatment, with itraconazole being the most commonly used.
- Itraconazole is typically administered at a dosage of 400 mg daily, divided into two doses, for a duration of 12 months. Hepatotoxicity is the primary chronic adverse effect associated with itraconazole therapy.[40] Extended treatment duration has been identified as a crucial factor for achieving a higher cure rate, with eumycetoma patients often requiring treatment ranging from 6 months to 3 years.[41]
- Newer azoles, including voriconazole (administered at a dosage of 400 to 600 mg/d) and posaconazole (at a dosage of 800 mg daily), have also been trialed and have demonstrated favorable clinical outcomes.[39][42][43] (B3)
Amphotericin B: The toxicity and requirement for hospitalization have significantly restricted the utilization of amphotericin B. Although liposomal amphotericin B has been used in certain cases in endemic regions, its efficacy has been inadequate, and the severe adverse effect of nephrotoxicity limits its application.[36] Intralesional administration of amphotericin B has demonstrated favorable outcomes in select cases with a solitary lesion; however, it is not an efficacious treatment option for multilobulated lesions due to uneven drug diffusion and the risk of dissemination.[44](B3)
Terbinafine: Administration of 500 mg of terbinafine twice daily for 24 to 48 weeks has resulted in significant clinical improvement in 80% of cases.[45]
Surgical Interventions
Authors of one study recommend a stepwise approach, beginning with the initial preoperative treatment of eumycetoma using itraconazole. Antifungal therapy promotes encapsulation of eumycetoma, facilitating better localization and surgical debridement. This approach allows for avoiding comprehensive, extensive, and disfiguring procedures.[17](B3)
Differential Diagnosis
The differential diagnosis should include the following:
- Lobomycosis: This is a chronic cutaneous fungal infection caused by Lacazia loboi endemic to Central and South America. Initially, lesions manifest as papules and advance to keloid-like formations, appearing as smooth nodules predominantly found on the hands, ears, and ankles. In contrast, mycetoma is characterized by sinus or fistula formation with the expulsion of granules.[46][47]
- Mycobacterium marinum: This is an atypical mycobacterial infection acquired through contact with contaminated swimming pools, lakes, or ocean water and is also known as "fish tank granuloma." Clinically, the infection presents with tender red nodules on the fingers or hands.[48]
- Chromoblastomycosis: This is a subcutaneous fungal infection caused by dematiaceous fungi commonly observed in tropical and subtropical climates. Chromoblastomycosis typically manifests in middle-aged men with crusted lesions affecting the lower extremities.[49]
- Histoplasmosis: This is a fungal infection characterized by umbilicated papules, nodules, or indurated ulcers. Associated lymphadenopathy is commonly observed. Risk factors for systemic involvement include immunosuppressed states.[50]
- Cutaneous tuberculosis: This condition is clinically heterogeneous and presents as non-healing nodules, ulcers, plaques, or draining lymph nodes in patients from endemic areas.[51]
Prognosis
Untreated eumycetoma follows a slow but inevitable progression.[49] In cases where this condition is not promptly recognized, or treatment is unavailable or unaffordable, initially painless eumycetoma can advance to limb destruction and necessitate amputation (see Image. Progressing Eumycetoma with Deep-Tissue Penetration). Studies reviewing multiple cases of eumycetomas have identified several positive prognostic factors, including longer duration of therapy and absence of relapse in patient history. Additionally, mycetomas measuring between 5 and 10 cm or greater than 10 cm, managed with a combination of medical and surgical treatment, are significant predictors of a favorable outcome.[17] Relapse of eumycetoma is common, especially among individuals with a disease duration exceeding 10 years and those with involvement outside of the feet. According to a machine-learning algorithm, individuals with a history of prior surgical excision, a family history of the condition, or employment as non-farmers are at an increased risk of recurrence.[54][55]
Complications
If left untreated, the infection can spread along fascial planes and affect muscle and bone, resulting in complications such as osteomyelitis or extension into deeper structures, which can render the organism more resistant to treatment (see Image. Advanced-Stage Eumycetoma With Gangrenous Features).[56][57] Moreover, the condition may cause significant deformities with associated psychosocial consequences.[58][59]
Deterrence and Patient Education
Considering the pathogenesis of this disease, wearing shoes can help prevent injuries that may lead to eumycetoma. Therefore, avoiding walking barefoot in highly endemic areas is advisable whenever possible. Shoes provide protection for the feet while walking or working in environments where exposure to fungal elements in water and soil is likely. Early detection and treatment, before the eumycetoma spreads deeper across fascial planes, can help reduce disabilities associated with eumycetoma and improve outcomes.
Enhancing Healthcare Team Outcomes
Eumycetoma often presents a diagnostic and treatment challenge. The condition arises following traumatic inoculation of filamentous fungi in individuals who walk barefoot in endemic regions. On physical examination, nonhealing, chronic nodules, and sinus tracts are commonly observed on the legs, persisting for many years. The availability of healthcare services in regions where eumycetoma is prevalent significantly influences the speed at which diagnosis and treatment can be initiated.
Patients with eumycetoma require collaboration with an interprofessional healthcare team comprising a dermatologist, an infectious disease specialist, and a surgeon for lesion debulking. Pharmacists are critical in ensuring appropriate dosing of oral antifungals during the initial stages of treatment. Dermatopathologists are involved in examining biopsy specimens histopathologically to establish an accurate diagnosis. Additional radiological examinations may be necessary for longstanding, widespread infections. Although definitive guidelines for managing eumycetoma are lacking, treatment regimens are derived from case series and a comprehensive review of current medical literature published in peer-reviewed journals.[17] The outcomes of eumycetoma rely on prompt diagnosis and timely management of the condition; hence, early consultation with interprofessional healthcare specialists is highly recommended.
Media
(Click Image to Enlarge)
Advanced-Stage Eumycetoma With Gangrenous Features. This image displays the advancement of eumycetoma to the foot bones of the left foot in a patient with advanced-stage disease.
(Click Image to Enlarge)
Histopathological View of Aspergillus niger. The microscopic image provides a detailed view of Aspergillus niger, highlighting its characteristic features such as wide, branching septate hyphae and well-formed conidial heads.
(Click Image to Enlarge)
Progressing Eumycetoma With Deep-Tissue Penetration. This image depicts a patient with progressing eumycetoma, showcasing deep-tissue penetration in the right foot.
References
Kuzucular E, Eren A, Isik E, Ozden F. Mycetoma (Madura foot): A Case Report of a Rare Tropical Disease in Turkey. The international journal of lower extremity wounds. 2023 Feb 22:():15347346231156642. doi: 10.1177/15347346231156642. Epub 2023 Feb 22 [PubMed PMID: 36814397]
Level 3 (low-level) evidenceSiddig EE, Nyuykonge B, Mhmoud NA, Abdallah OB, Bahar MEN, Ahmed ES, Nyaoke B, Zijlstra EE, Verbon A, Bakhiet SM, Fahal AH, van de Sande WWJ. Comparing the performance of the common used eumycetoma diagnostic tests. Mycoses. 2023 May:66(5):420-429. doi: 10.1111/myc.13561. Epub 2023 Jan 17 [PubMed PMID: 36583225]
Singh B, Gehlot R, Saxena M, Bharwani N, Raichandani K, Bhati M. An unusual presentation of mycetoma around knee joint as a subcutaneous mass - A case report. Journal of orthopaedic case reports. 2022 Oct:12(10):22-25. doi: 10.13107/jocr.2022.v12.i010.3350. Epub [PubMed PMID: 36874900]
Level 3 (low-level) evidenceBahar Moni AS, Hoque MM. Chronic Painless, Multiple Papulo-Nodular Skin Lesion at Foot Resembles Mycetoma Infection (Madura Foot): A Case Report. The international journal of lower extremity wounds. 2023 Sep:22(3):616-619. doi: 10.1177/15347346211030753. Epub 2021 Jul 5 [PubMed PMID: 34223771]
Level 3 (low-level) evidenceKombo EB. [Uncommon signs of mycetoma]. The Pan African medical journal. 2019:34():163. doi: 10.11604/pamj.2019.34.163.20300. Epub 2019 Nov 26 [PubMed PMID: 32153703]
White EA, Patel DB, Forrester DM, Gottsegen CJ, O'Rourke E, Holtom P, Charlton T, Matcuk GR. Madura foot: two case reports, review of the literature, and new developments with clinical correlation. Skeletal radiology. 2014 Apr:43(4):547-53. doi: 10.1007/s00256-013-1751-z. Epub 2013 Oct 23 [PubMed PMID: 24150831]
Level 3 (low-level) evidenceSawatkar GU, Wankhade VH, Supekar BB, Singh RP, Bhat DM, Tankhiwale SS. Mycetoma: A Common Yet Unrecognized Health Burden in Central India. Indian dermatology online journal. 2019 May-Jun:10(3):256-261. doi: 10.4103/idoj.IDOJ_358_18. Epub [PubMed PMID: 31149567]
Relhan V, Mahajan K, Agarwal P, Garg VK. Mycetoma: An Update. Indian journal of dermatology. 2017 Jul-Aug:62(4):332-340. doi: 10.4103/ijd.IJD_476_16. Epub [PubMed PMID: 28794542]
Foltz KD, Fallat LM. Madura foot: atypical finding and case presentation. The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons. 2004 Sep-Oct:43(5):327-31 [PubMed PMID: 15480410]
Level 3 (low-level) evidenceDiongue K, Diallo MA, Sarr L, Seck MC, Bréchard L, Ndiaye M, Badiane AS, Ranque S, Ndiaye D. Pulmonary Madurella mycetomatis mycetoma secondary to knee eumycetoma, Senegal. PLoS neglected tropical diseases. 2021 Mar:15(3):e0009238. doi: 10.1371/journal.pntd.0009238. Epub 2021 Mar 25 [PubMed PMID: 33764976]
Ahmed AO, van Leeuwen W, Fahal A, van de Sande W, Verbrugh H, van Belkum A. Mycetoma caused by Madurella mycetomatis: a neglected infectious burden. The Lancet. Infectious diseases. 2004 Sep:4(9):566-74 [PubMed PMID: 15336224]
Level 3 (low-level) evidenceOlenski M, Halliday C, Gullifer J, Martinez E, Crowe A, Sheorey H, Darby J. A Case of Trauma-Induced Falciformispora lignatilis Eumycetoma in a Renal Transplant Recipient. Tropical medicine and infectious disease. 2021 Aug 3:6(3):. doi: 10.3390/tropicalmed6030144. Epub 2021 Aug 3 [PubMed PMID: 34449744]
Level 3 (low-level) evidenceFahal AH. Mycetoma: a thorn in the flesh. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2004 Jan:98(1):3-11 [PubMed PMID: 14702833]
Sahu BK, Nag HL. An Illustrative Report of Three Cases of Madura Foot with Diagnostic and Treatment Features. Journal of orthopaedic case reports. 2021 Nov:11(11):74-78. doi: 10.13107/jocr.2021.v11.i11.2522. Epub [PubMed PMID: 35415109]
Level 3 (low-level) evidenceAbdelrahman M, Saad EA, Abdulla GM, Mohamed A. Reconstructive Surgery for Mycetoma: Is There a Need to Establish an Algorithm? Plastic and reconstructive surgery. Global open. 2019 Apr:7(4):e2197. doi: 10.1097/GOX.0000000000002197. Epub 2019 Apr 24 [PubMed PMID: 31321187]
Emmanuel P, Dumre SP, John S, Karbwang J, Hirayama K. Mycetoma: a clinical dilemma in resource limited settings. Annals of clinical microbiology and antimicrobials. 2018 Aug 10:17(1):35. doi: 10.1186/s12941-018-0287-4. Epub 2018 Aug 10 [PubMed PMID: 30097030]
Nenoff P, van de Sande WW, Fahal AH, Reinel D, Schöfer H. Eumycetoma and actinomycetoma--an update on causative agents, epidemiology, pathogenesis, diagnostics and therapy. Journal of the European Academy of Dermatology and Venereology : JEADV. 2015 Oct:29(10):1873-83. doi: 10.1111/jdv.13008. Epub 2015 Feb 27 [PubMed PMID: 25726758]
Level 3 (low-level) evidenceSow D, Ndiaye M, Sarr L, Kanté MD, Ly F, Dioussé P, Faye BT, Gaye AM, Sokhna C, Ranque S, Faye B. Mycetoma epidemiology, diagnosis management, and outcome in three hospital centres in Senegal from 2008 to 2018. PloS one. 2020:15(4):e0231871. doi: 10.1371/journal.pone.0231871. Epub 2020 Apr 24 [PubMed PMID: 32330155]
Ahmed SA, El-Sobky TA, de Hoog S, Zaki SM, Taha M. A scoping review of mycetoma profile in Egypt: revisiting the global endemicity map. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2023 Jan 3:117(1):1-11. doi: 10.1093/trstmh/trac085. Epub [PubMed PMID: 36084235]
Level 2 (mid-level) evidenceDeveloux M. Epidemiologic Aspects of Mycetoma in Africa. Journal of fungi (Basel, Switzerland). 2022 Nov 29:8(12):. doi: 10.3390/jof8121258. Epub 2022 Nov 29 [PubMed PMID: 36547591]
Hulin M, Lamoureux C, Sainte-Rose V, Drak Alsibai K, Demar M, Couppie P, Blaizot R. Fungal and bacterial mycetoma in migrants from Haiti: A case series. Travel medicine and infectious disease. 2023 Mar-Apr:52():102530. doi: 10.1016/j.tmaid.2022.102530. Epub 2022 Dec 17 [PubMed PMID: 36539021]
Level 3 (low-level) evidenceNyuykonge B, Siddig EE, Konings M, Bakhiet S, Verbon A, Klaassen CHW, Fahal AH, van de Sande WWJ. Madurella mycetomatis grains within a eumycetoma lesion are clonal. Medical mycology. 2022 Jul 29:60(7):. doi: 10.1093/mmy/myac051. Epub [PubMed PMID: 35833294]
Abushouk A, Nasr A, Masuadi E, Allam G, Siddig EE, Fahal AH. The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis. PLoS neglected tropical diseases. 2019 Apr:13(4):e0007098. doi: 10.1371/journal.pntd.0007098. Epub 2019 Apr 4 [PubMed PMID: 30946748]
Seyedmousavi S, Netea MG, Mouton JW, Melchers WJ, Verweij PE, de Hoog GS. Black yeasts and their filamentous relatives: principles of pathogenesis and host defense. Clinical microbiology reviews. 2014 Jul:27(3):527-42. doi: 10.1128/CMR.00093-13. Epub [PubMed PMID: 24982320]
Level 3 (low-level) evidenceFahal AH, el Toum EA, el Hassan AM, Mahgoub ES, Gumaa SA. The host tissue reaction to Madurella mycetomatis: new classification. Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology. 1995 Jan-Feb:33(1):15-7 [PubMed PMID: 7650573]
Level 3 (low-level) evidenceSamaila MO, Abdullahi K. Cutaneous manifestations of deep mycosis: an experience in a tropical pathology laboratory. Indian journal of dermatology. 2011 May:56(3):282-6. doi: 10.4103/0019-5154.82481. Epub [PubMed PMID: 21772588]
Ansari F, Singh S, Bhardwaj A, Budania A, Bains A, Nalwa A, Khera S, Elhence P, Patel A, Yadav T, Khera P. Clinical triad with multi-biopsy histopathology as a reliable diagnostic marker of mycetomas: a retrospective review from a tertiary care center. International journal of dermatology. 2023 Jan:62(1):88-96. doi: 10.1111/ijd.16384. Epub 2022 Aug 28 [PubMed PMID: 36030528]
Level 2 (mid-level) evidenceBen Tekaya A, Yosra G, Saidane O, Rouached L, Bouden S, Tekaya R, Mahmoud I, Abdelmoula L. Eumycotic mycetoma involving the right foot: A new Tunisian case. Clinical case reports. 2022 Sep:10(9):e6327. doi: 10.1002/ccr3.6327. Epub 2022 Sep 12 [PubMed PMID: 36172334]
Level 3 (low-level) evidenceSiddig EE, Ahmed A, Hassan OB, Bakhiet SM, Verbon A, Fahal AH, van de Sande WWJ. Using a Madurella mycetomatis-specific PCR on grains obtained via non-invasive fine-needle aspirated material is more accurate than cytology. Mycoses. 2023 Jun:66(6):477-482. doi: 10.1111/myc.13572. Epub 2023 Feb 19 [PubMed PMID: 36740735]
Siddig EE, El Had Bakhait O, El Nour Hussein Bahar M, Siddig Ahmed E, Bakhiet SM, Motasim Ali M, Babekir Abdallah O, Ahmed Hassan R, Verbon A, van de Sande WWJ, Fahal AH. Ultrasound-guided fine-needle aspiration cytology significantly improved mycetoma diagnosis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2022 Oct:36(10):1845-1850. doi: 10.1111/jdv.18363. Epub 2022 Jul 6 [PubMed PMID: 35748131]
Sonone PP, Hiwale KM. Histopathological Diagnosis of Eumycetoma With Paraspinal Sinuses: A Rare Case Report. Cureus. 2022 Sep:14(9):e29634. doi: 10.7759/cureus.29634. Epub 2022 Sep 26 [PubMed PMID: 36320972]
Level 3 (low-level) evidencevan de Sande WW, Fahal AH, Goodfellow M, Mahgoub el S, Welsh O, Zijlstra EE. Merits and pitfalls of currently used diagnostic tools in mycetoma. PLoS neglected tropical diseases. 2014 Jul:8(7):e2918. doi: 10.1371/journal.pntd.0002918. Epub 2014 Jul 3 [PubMed PMID: 24992636]
Sen A, Pillay RS. Case report: Dot-in-circle sign - An MRI and USG sign for "Madura foot". The Indian journal of radiology & imaging. 2011 Oct:21(4):264-6. doi: 10.4103/0971-3026.90684. Epub [PubMed PMID: 22223936]
Level 3 (low-level) evidenceBentaleb D, Mahdar I, Noureddine L, Mellouki A, Sabiri M, Lembarki G, Essodegui F, Regragui M. Diagnostic imaging of foot mycetomas: A report on two cases. Radiology case reports. 2022 May:17(5):1817-1823. doi: 10.1016/j.radcr.2022.02.081. Epub 2022 Mar 29 [PubMed PMID: 35369545]
Level 3 (low-level) evidenceBahar ME, Bakheet OELH, Fahal AH. Mycetoma imaging: the best practice. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2021 Apr 14:115(4):387-396. doi: 10.1093/trstmh/traa178. Epub [PubMed PMID: 33537774]
Welsh O, Al-Abdely HM, Salinas-Carmona MC, Fahal AH. Mycetoma medical therapy. PLoS neglected tropical diseases. 2014 Oct:8(10):e3218. doi: 10.1371/journal.pntd.0003218. Epub 2014 Oct 16 [PubMed PMID: 25330342]
Level 3 (low-level) evidenceVenugopal PV, Venugopal TV. Treatment of eumycetoma with ketoconazole. The Australasian journal of dermatology. 1993:34(1):27-9 [PubMed PMID: 8240184]
Paugam A, Tourte-Schaefer C, Keïta A, Chemla N, Chevrot A. Clinical cure of fungal madura foot with oral itraconazole. Cutis. 1997 Oct:60(4):191-3 [PubMed PMID: 9347233]
Level 3 (low-level) evidenceLacroix C, de Kerviler E, Morel P, Derouin F, Feuilhade de Chavin M. Madurella mycetomatis mycetoma treated successfully with oral voriconazole. The British journal of dermatology. 2005 May:152(5):1067-8 [PubMed PMID: 15888176]
Level 3 (low-level) evidenceFahal AH, Rahman IA, El-Hassan AM, Rahman ME, Zijlstra EE. The safety and efficacy of itraconazole for the treatment of patients with eumycetoma due to Madurella mycetomatis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2011 Mar:105(3):127-32. doi: 10.1016/j.trstmh.2010.11.008. Epub 2011 Jan 17 [PubMed PMID: 21247608]
Fahal A, Mahgoub el S, El Hassan AM, Abdel-Rahman ME. Mycetoma in the Sudan: an update from the Mycetoma Research Centre, University of Khartoum, Sudan. PLoS neglected tropical diseases. 2015 Mar:9(3):e0003679. doi: 10.1371/journal.pntd.0003679. Epub 2015 Mar 27 [PubMed PMID: 25816316]
Loulergue P, Hot A, Dannaoui E, Dallot A, Poirée S, Dupont B, Lortholary O. Successful treatment of black-grain mycetoma with voriconazole. The American journal of tropical medicine and hygiene. 2006 Dec:75(6):1106-7 [PubMed PMID: 17172376]
Level 3 (low-level) evidenceNegroni R, Tobón A, Bustamante B, Shikanai-Yasuda MA, Patino H, Restrepo A. Posaconazole treatment of refractory eumycetoma and chromoblastomycosis. Revista do Instituto de Medicina Tropical de Sao Paulo. 2005 Nov-Dec:47(6):339-46 [PubMed PMID: 16553324]
Level 3 (low-level) evidenceCastro LG, Piquero-Casals J. Clinical and mycologic findings and therapeutic outcome of 27 mycetoma patients from São Paulo, Brazil. International journal of dermatology. 2008 Feb:47(2):160-3. doi: 10.1111/j.1365-4632.2008.03447.x. Epub [PubMed PMID: 18211487]
N'diaye B, Dieng MT, Perez A, Stockmeyer M, Bakshi R. Clinical efficacy and safety of oral terbinafine in fungal mycetoma. International journal of dermatology. 2006 Feb:45(2):154-7 [PubMed PMID: 16445509]
Ramírez Soto MC, Malaga G. Subcutaneous mycoses in Peru: a systematic review and meta-analysis for the burden of disease. International journal of dermatology. 2017 Oct:56(10):1037-1045. doi: 10.1111/ijd.13665. Epub 2017 Jul 3 [PubMed PMID: 28670680]
Level 1 (high-level) evidencePang KR, Wu JJ, Huang DB, Tyring SK. Subcutaneous fungal infections. Dermatologic therapy. 2004:17(6):523-31 [PubMed PMID: 15571502]
Zeegelaar JE, Faber WR. Imported tropical infectious ulcers in travelers. American journal of clinical dermatology. 2008:9(4):219-32 [PubMed PMID: 18572973]
Seas C, Legua P. Mycetoma, chromoblastomycosis and other deep fungal infections: diagnostic and treatment approach. Current opinion in infectious diseases. 2022 Oct 1:35(5):379-383. doi: 10.1097/QCO.0000000000000870. Epub 2022 Aug 3 [PubMed PMID: 35942857]
Level 3 (low-level) evidenceKöhler JR, Hube B, Puccia R, Casadevall A, Perfect JR. Fungi that Infect Humans. Microbiology spectrum. 2017 Jun:5(3):. doi: 10.1128/microbiolspec.FUNK-0014-2016. Epub [PubMed PMID: 28597822]
Aissat FZ, Denning DW. Fungal infections in Algeria. Mycoses. 2023 Jul:66(7):594-603. doi: 10.1111/myc.13585. Epub 2023 Apr 2 [PubMed PMID: 37005355]
Tomczyk S, Deribe K, Brooker SJ, Clark H, Rafique K, Knopp S, Utzinger J, Davey G. Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis. PLoS neglected tropical diseases. 2014:8(11):e3285. doi: 10.1371/journal.pntd.0003285. Epub 2014 Nov 13 [PubMed PMID: 25393620]
Level 1 (high-level) evidenceMorand JJ. [Foot health in the tropics]. Medecine tropicale : revue du Corps de sante colonial. 2008 Apr:68(2):111-8 [PubMed PMID: 18630042]
Ray A, Aayilliath K A, Banerjee S, Chakrabarti A, Denning DW. Burden of Serious Fungal Infections in India. Open forum infectious diseases. 2022 Dec:9(12):ofac603. doi: 10.1093/ofid/ofac603. Epub 2022 Dec 26 [PubMed PMID: 36589484]
Wadal A, Elhassan TA, Zein HA, Abdel-Rahman ME, Fahal AH. Predictors of Post-operative Mycetoma Recurrence Using Machine-Learning Algorithms: The Mycetoma Research Center Experience. PLoS neglected tropical diseases. 2016 Oct:10(10):e0005007. doi: 10.1371/journal.pntd.0005007. Epub 2016 Oct 31 [PubMed PMID: 27798643]
Maheshwari S, Figueiredo A, Narurkar S, Goel A. Madurella mycetoma--a rare case with cranial extension. World neurosurgery. 2010 Jan:73(1):69-71. doi: 10.1016/j.surneu.2009.06.014. Epub 2009 Oct 9 [PubMed PMID: 20452871]
Level 3 (low-level) evidenceAwad A, Alnaser A, Abd-Elmaged H, Abdallah R, Khougali HS. Eumycetoma Osteomyelitis Calcaneus in Adolescent; report of case and literature review. BMC infectious diseases. 2021 Sep 23:21(1):995. doi: 10.1186/s12879-021-06695-3. Epub 2021 Sep 23 [PubMed PMID: 34556037]
Level 3 (low-level) evidenceFahal AH, Sabaa AH. Mycetoma in children in Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2010 Feb:104(2):117-21. doi: 10.1016/j.trstmh.2009.07.016. Epub 2009 Aug 28 [PubMed PMID: 19716573]
Saleh R, Nong I, Guatama A, Putro GD, Azis HS. Long term follow-up of Maduromycosis treatment: A case review. International journal of surgery case reports. 2021 May:82():105956. doi: 10.1016/j.ijscr.2021.105956. Epub 2021 May 3 [PubMed PMID: 33984729]
Level 3 (low-level) evidence