A surgeon’s trial success of curing pedal eumycetoma

Abstract

Mycetoma is a chronic infection of underlying fungal (eumycetoma) or bacterial (actinomycetoma) origin. It is characterised by a clinical triad of tumour-like swelling, actively draining sinuses and macroscopic grains of characteristic colours.

We the case of a 66-year-old woman on immunosuppressive therapy presenting with eumycetoma of the foot (Madura foot). The fungal organism cultured was Acrophialophora fusispora.

This case was managed with a combination of extensive surgical debridement, and packing with calcium sulfate (Stimulan) beads impregnated with vancomycin and voriconazole. As far as the authors are aware, this is a novel adjunct to the surgical treatment of deep fungal infection in the foot.

Eumycetoma treated with surgery and oral antifungal therapy leads to cure rates of 25%–35%. This novel treatment seems to bear further investigation for the potential to improve cure rates. At 8 months follow-up, our patient appears to be making good progress with no current signs of recurrence.

Background

Mycetoma, formerly known as Madura foot, is a chronic granulomatous infection caused by fungi (eumycetoma) or bacteria (actinomycetoma).¹ Common organisms causing eumycetoma involved are Madurella mycetomatis and in actinomycetoma, Actinomadura madurae, respectively.²

Mycetoma is characterised by the triad of a subcutaneous mass, sinuses and granular discharge.³ This condition has recently been placed on the WHO list of neglected diseases because it affects poorer and remote populations who do not have access to diagnostic or treatment facilities and shows slow and chronic disease progression.

Geographically it is seen between latitudes 15° South and 30° North,⁴ and is most commonly found in India, Mexico and Sudan. Eumycetoma comprises 40% of mycetomas worldwide.⁵

Treatment of actinomycetoma can be effective if diagnosed early, with cure rates of 90%, but cure rates for eumycetoma are much lower at 25%–35%.⁶ The current treatment of eumycetoma is surgical debridement with adjuvant medical treatment, but if this does not eradicate infection, amputation may be the only treatment option.⁷

Case presentation

A 66-year-old woman of Pakistani origin was referred to our department by a dermatologist for an opinion on a long-standing lesion of the right foot (figure 1). Her medical history is complicated with previous renal transplant for renal failure in 2007 and she was immunosuppressed with azathioprine and prednisolone. Additionally, she has had tuberculosis, cytomegalovirus and suffers from osteoporosis.

Figure 1.

Photographs showing skin lesion over right ankle.

The infection first presented as a macular papular lesion inferior and posterior to the medial malleolus of the right ankle around 2011 as part of skin surveillance following her renal transplant. It was excised and remained dormant until 2014. The lesion returned as a discharging sinus and was thought to be a possible squamous cell carcinoma of the skin owing to its keratinised appearance.

She had excision and two separate biopsies at the time which showed it to be, in fact, a cutaneous fungal lesion with additional bacterial infection with a skin commensal, Staphylococcus caprae. She underwent oral therapy with fluconazole and doxycycline which appeared to reduce discharge but did not entirely clear the lesion.

Additional deep tissue biopsy was taken in mid-2015 which showed extensive hyphae for which she was started on oral voriconazole for 6 months to good effect.

However, following cessation of antifungal therapy, the lesion returned and she was referred to the orthopaedic foot and ankle clinic for further advice and treatment.

Investigations

MRI scanning (figure 2A,B) revealed a large intraosseous mycetoma in the body of the calcaneus in continuity with extraosseous mycetoma superficial and deep to the plantar fascia.

Figure 2.

MRI demonstrating lesions with peripheral hypointense rim with central hyperintense representing mycetoma grains as thick white arrows. Thin white arrows show the characteristic ‘dot in circle’ sign: (A) sagittal view of calcaneum; (B) coronal view of calcaneum.

Differential diagnosis

1. Chronic bacterial osteomyelitis

2. Neoplasia

3. Sporotrichosis

4. Tuberculosis

5. Coccidioidmycosis

Treatment

Extensive surgical debridement of the hind and midfoot was performed (figure 3A). Once all grains were meticulously removed and wound irrigated, the bony defect in the calcaneus and the adjacent soft tissues were packed with calcium sulfate beads (Stimulan; Biocomposites, Staffordshire, UK) (figure 3B). Five millilitres of beads were loaded with 500 mg vancomycin and 5 ml loaded with 200 mg voriconazole. Dressings and a plaster cast were applied following closure of the surgical wound.

Figure 3.

Photograph showing: (A) mass post debridement; (B) defect filled with Stimulan beads containing antifungal and antibacterial medication.

Outcome and follow-up

Following the procedure, she made a full recovery and was discharged home 5 days after her procedure. At 2-week follow-up, the wound was noted to have healed nicely without evidence of infection.

At 8 weeks, postoperatively showed satisfactory progress on radiographs and a clean dry wound. She had her plaster cast removed and was advised to mobilise full weight bearing.

She was commenced on oral voriconazole 200 mg twice daily for 1 year. Eight months following surgery, X-rays (figure 4A–C) reveal satisfactory bone healing with radiological union and no soft tissue swelling or sign of recurrence. She is walking without pain and does not use a walking aid.

Figure 4.

Radiography at: (A) initial presentation showing osseous lesion; (C) postsurgery containing beads; (B) 8 months follow-up.

Discussion

Diagnosis and treatment of mycetoma is often delayed. It is a slowly developing disease that may not become clinically apparent for years or even decades. Many different fungi can cause eumycetoma, thus treatment requires isolation of the causative organism and sensitivity testing to antifungal drugs. This may not be possible in areas with low socioeconomic status and a lack of health education and facilities.

In our case, Acrophialophora fusispora was cultured from a punch biopsy of the skin lesion performed by the dermatologist. Although there was a strong clinical suspicion of active fungal infection at the time of surgery, fungal cultures from multiple deep tissue samples were negative. This species is found in soil, especially in India, and has been previously reported as a human pathogen.⁸ There are three previous cases reported in the literature; two presenting with a brain abscess and one with a retained contact lens causing keratouveitis. Interestingly, these patients were immune incompetent.⁹ This is in contrast to our patient who has history of renal transplant, CMV and TB and is on immunosuppressive therapy with azathioprine and prednisolone.

Secondary bacterial infection with S caprae and S aureus was found in our patient’s mycetoma. This is believed to cause pain and increased morbidity.¹⁰ Ahmed and Abugroun suggest that some patients with concomitant bacterial infection develop bacteraemia or septicaemia.¹⁰ This may lead to failure of antifungal treatment or cause a pathological fracture.

Conventional osteomyelitis treatment involving surgical debridement of infected and necrotic tissue and administration systemic antibiotics can fail in up to 10% of cases. This may be as systemic antibiotic treatment may be ineffective with poorly vascularised infected and osteonecrotic tissues.¹¹ The use of calcium sulfate granules (Stimulan; Biocomposites, Staffordshire, UK) loaded with vancomycin and voriconazole is a novel adjunct to conventional surgical debridement of eumycetoma that has not been reported in literature before. Gradual elution of the antifungal agent from the calcium sulfate beads over the course of the first few weeks postoperatively should lead to higher tissue levels than can be achieved with oral therapy alone. We elected to keep our patient on oral voriconazole 200 mg twice daily for 1 year postoperatively, although the optimal duration of treatment is unknown. The National Health Service cost for a 1-year course is £28671. In comparison, the extra cost of using voriconazole-loaded and vancomycin-loaded calcium sulfate beads to fill dead space during surgery is relatively modest, at £1612 for the calcium sulfate bead kit, £77 for the voriconazole and £17 for the vancomycin. The doses used were based on recommendations from the manufacturer of the calcium sulfate bead kit.¹² Locally delivered biodegradable antibiotic system can theoretically offer dead space management and local infection therapy.^12–14

Eumycetoma carries a significant risk of amputation in endemic areas and even when treated in affluent countries. Amputation carries high lifetime costs for care, rehabilitation and prosthetics. It is not culturally accepted in many of the areas where mycetoma is endemic. This novel adjuvant treatment may improve cure rates and is worthy of further investigation. It is not clear at this stage whether a prolonged course of oral antifungal drugs is necessary postoperatively, which could help to reduce total costs in a resource-poor setting.

Learning points.

• Mycetoma is difficult to manage and has a significant morbidity.

• Recurrent infection can lead to the need for amputation.

• Recurrence with conventional treatment is common.

• Diagnosing the organism is fundamental for the success of treatment.

• Mycetoma should be considered in failed management of pedal lesions.