Madura foot was recognized as a disease entity by Gill in the year 1842 at Madurai, India and was later termed ‘mycetoma’ by Carter in 1880 (6). It commonly affects those occupations that are in close contact with soil and vegetations such as farmers, cattle breeders, agricultural workers and poultry farmers. It usually involves parts of the body that are exposed to the soil like hands, feet and lower legs. Transdermal inoculation is the most common route of transmission, usually following trauma or penetrating injury (7).
It is prevalent in patients between 20 to 40 years of age and demonstrates male predilection with a reported male-female ratio of 3.5: 1 (8). It is a sinister disease that painlessly spreads through the soft tissue to involve bones, rendering conservative management options futile. Clinically, it presents with a triad of features- painless foot swelling, multiple sinuses and discharging specific-colored grains (4). Though actinomycetoma and eumycetoma present with similar features, the former exhibits a rapid progressive course resulting in locally advanced and disseminated infection (9). Infection progresses in four stages (4). The first stage of the disease is incubation which can vary from a few weeks to years. Subsequently, the patients develop nonspecific features of local cellulitis like swelling and pain. As the pathogen proliferates in the subcutaneous plane, microabcesses with surrounding granulation tissue result in formation of subcutaneous nodules. As these nodules increase in size, they erupt the overlying skin surface forming discharging sinuses. Eventually, the disease extends into deeper tissue planes and involves bones causing significant soft tissue and osseous destruction. Deformity soon ensues destruction.
In the advanced stages, diagnosis can be made readily based on classical clinical features. During the early indolent course of the disease, it is often misdiagnosed and unsuccessfully treated as common bacterial cellulitis. At the time of diagnosis, the disease is usually advanced with extensive soft tissue and bone involvement necessitating amputation. Hence, the challenge lies in early diagnosis of the disease.
Radiological investigations, especially ultrasonography (USG) and magnetic resonance imaging (MRI) are indispensable modalities tools for early diagnosis. Plain radiographs can be normal in the early stage of disease but can demonstrate bone involvement and soft tissue thickening. However, computed tomography (CT) helps in better characterization of the pattern of bone involvement, periosteal reaction, presence of osteoporosis and bone destruction (10). Magnetic resonance imaging (MRI) is the imaging modality of choice aiding in excellent characterization of the soft tissue, associated extensions and infiltration, bone involvement and bone marrow edema. It also plays an indispensable role in pretherapeutic staging, evaluation of associated complications and therapeutic response assessment. Bone scintigraphy is another valuable tool for assessment of therapeutic response (10).
The spectrum of radiological features comprises of various patterns of soft tissue and bone involvement. USG and MRI are the preferred tools for soft tissue characterization. On USG, it presents as an ill- defined hypoechoic infiltrative mass. Few authors have described increased color flow and Doppler signals within soft tissue which can be secondary to inflammation (11, 12). On MRI, the soft tissue appears hyperintense on T2, PD FS and STIR sequences. It predominantly involves the subcutaneous tissue but frequently infiltrates the muscles and deeper soft tissue due to its aggressive nature (13), as observed in our case. The presence of ‘dot-in-circle' sign has been described as a specific hallmark for pedal mycetoma (11–14). It has been described in cases of both eumycetoma and actinomycetoma. The basis of ‘dot-in-circle' sign depends on the pathological organization of the granuloma which comprises of a central core of microbial elements (fungal hyphae or filamentous bacteria) surrounded by granulation tissue and chronic inflammatory infiltrate with a peripheral rim of fibrosis (Fig. 6) (15). It was first described by Sarris I et al in 2003 (16). However, the earlier available case reports also describe similar findings (17, 18). On USG, it appears as a hypoechoic lesion with a central hyperechoic core and peripheral hypoechoic rim (Fig. 7). On MRI, this sign is best described on T2 FS, PD FS and STIR sequences in which these lesions appear hyperintense with a central hypointense focus and a peripheral hypointense rim (Fig. 8). T1 FS post contrast images have also been described to depict ‘dot-in-circle' sign but demonstrate no obvious advantage over non contrast sequences (15). However, post contrast images can additionally demonstrate the actual extent of soft tissue infiltration, associated collections, disease activity and subtle bone involvement. Diffusion weighted imaging (DWI) can aid in assessment of therapeutic response. Though few authors have not specifically reported ‘dot-in-circle' sign, Jimenez AL et al (19) reported the absence of the same in a case of eumycetoma which was initially misdiagnosed as synovial sarcoma. The presence of sinus tracts, hypoechoic on USG and hyperintense on T2/ STIR is another feature of mycetoma.
Bone involvement includes bone destruction, sclerosis, periosteal reaction and resultant deformities. As a general observation, most authors have reported aggressive patterns of bone destruction of which moth- eaten pattern and permeative type are the most common (11, 20–25). Aggressive forms of periosteal reaction such as interrupted, lamellated and spiculated patterns have been described as frequent associations (11, 15, 20, 23–25). As in our case, few authors have also reported nonaggressive solid form of periosteal reaction (11, 26, 27). Martinez EI et al (28) described ‘snow melting’ pattern of bone involvement characterized by lytic bone destruction with surrounding florid dense sclerosis. The presence of bone marrow edema without obvious cortical involvement or bone destruction can represent early involvement. Hoogervorst LA et al (29) reported noncontiguous disseminated small hypointense lesions scattered within the tibial bone marrow in an immunocompromised patient without any bone involvement. Advanced long term disease results in extensive osteolysis, sclerosis and bony ankylosis (23). The salient radiological features that have been described in the earlier literature are summarized in table 1.
Distinctive patterns of bone involvement in actinomycetoma and eumycetoma have been observed (15, 20). Eumycetoma is associated with larger (usually > 1 cm in size) intraosseous cavities while Actinomycetoma causes moth- eaten pattern of bone destruction i.e., multiple punctate well-defined cavities. Gameraddin M et al (30) studied the differential sonographic and Doppler characteristics of eumycetoma and actinomycetoma. They reported that eumycetoma was associated with multiple aggregated grains, more heterogeneous echotexture and higher vascularity in comparison to actinomycetoma.
Radiological staging of the disease is imperative for planning the treatment and patient counseling. In 2003, Abd El Bagi ME (31) devised a radiography- based system for staging bone involvement in pedal mycetoma (Table 2). Subsequently in 2013, El Shamy ME et al (32) proposed a detailed MRI- based mycetoma skin, muscle, bone (MSMB) grading system (Table 3) which comprises of three subscores- skin (scores 0–4), muscle (0–3) and bone (0–3). Out of a total score of 10, a score of 1–3 is considered mild, 4–7 is considered moderate and 8–10 is considered severe.
Imaging also aids in evaluating the therapeutic response in patients on conservative management (10, 33). Radiological features of healing are remodeling and sclerosis of the active edges of erosions, ossification of bone cavities and solid periosteal reaction, generalized bone sclerosis, resolution of bone marrow signal alteration, disappearance of granulomata (showing ‘dot-in-circle' appearance), reduced heterogeneity of soft tissue enhancement, normalization of diffusion restriction and normalization of increased uptake on bone scintigraphy.
Due to painless and quiescent progression of the disease, numerous patients present with complications even at the time of initial diagnosis. Complications include periostitis, osteomyelitis, arthritis, bone destruction resulting in deformity, secondary bacterial infection, bacteremia and septicemia (9, 34).
Differential diagnoses include diabetic foot, localized bacterial cellulitis, osteomyelitis, Charcot arthropathy, venous thrombosis, tuberculosis and vascular tumors and malformations. Among these conditions, soft tissue collection with bone fragments in osteomyelitis, rice bodies in tuberculosis and phleboliths in vascular malformations can mimic ‘dot-in-circle' appearance. Clinicoradiological features that aid in differentiating these conditions are enumerated in table 4.
Treatment of pedal mycetoma depends on the causative pathogen and stage of the disease. Actinomycetoma is treated with a combined regimen of antimicrobial agents including co-trimoxazole, dapsone, amikacin and tetracycline (35, 36). Drug therapy of eumycetoma involves azole derivatives (itraconazole, voriconazole, fluconazole and miconazole) and co-trimoxazole. Surgical debulking of the disease might be necessary in case of larger lesions (37). Age > 59 years, lesion of size > 10 cm, duration of disease > 5 years and positive family history are predictors of recurrence following surgical debulking or excision (38). Locally advanced disease with bone involvement might require amputation of the limb.