Buruli Ulcer

A chronic, progressive necrotising skin and soft tissue infection caused by Mycobacterium ulcerans, an environmental mycobacterium. It produces a potent exotoxin (mycolactone) responsible for extensive tissue necrosis, characteristically with a striking absence of pain in the great majority of cases.

It is endemic predominantly to specific regions of West and Central Africa, with additional recognised endemic foci in parts of Australia, Southeast Asia and South America.

The mechanism of transmission is incompletely understood. It is believed to involve environmental exposure, particularly proximity to slow moving or stagnant freshwater bodies, with possible insect vector involvement.

It is the third commonest mycobacterial infection worldwide after tuberculosis and leprosy. Delayed diagnosis and treatment cause substantial morbidity and disfigurement, so prompt recognition matters.

Pathophysiology

• Mycolactone, a unique polyketide toxin produced by Mycobacterium ulcerans, diffuses through surrounding tissue. It has extensive cytotoxic and immunosuppressive local effects.
• It produces progressive coagulative necrosis of the subcutaneous fat and overlying skin while suppressing the local immune and inflammatory response.
• This accounts for the extensive, undermined tissue destruction and the striking absence of significant pain and inflammatory signs. The combination frequently contributes to delayed presentation and diagnosis.
• The precise mode of transmission remains incompletely established. Environmental exposure to specific freshwater sources in endemic regions is strongly implicated.
• Some evidence supports a role for aquatic insects (including certain water bugs) as a potential vector or environmental reservoir.
• Person to person transmission does not occur, which distinguishes the epidemiological approach from many other mycobacterial infections.

• The disease typically begins as a painless, firm subcutaneous nodule or area of oedematous plaque, most commonly on an exposed limb.
• Without treatment, it progresses over weeks to characteristic ulceration with undermined, ragged edges and a necrotic base. This reflects toxin mediated subcutaneous tissue destruction extending well beyond the visible skin margin.
• The striking absence of significant pain, despite often extensive underlying tissue destruction, is a defining and diagnostically valuable feature.
• It can also delay presentation, because the lesion creates little symptomatic urgency. This is particularly relevant in resource limited endemic settings with limited access to healthcare.
• Untreated disease can progress to extensive ulceration affecting a substantial area of the limb, with risk of secondary bacterial infection.
• In advanced, longstanding disease, significant scarring and contracture cause severe functional impairment and disability. Osteomyelitis from direct bony extension occurs rarely.
• The World Health Organization clinical categorisation guides prognostic assessment and the intensity of treatment and monitoring.
• Category one is a single small lesion. Category two is a larger, non ulcerated or ulcerated plaque or oedematous lesion.
• Category three is more extensive, disseminated, or multifocal disease, or lesions at high risk anatomical sites including the face.

• In an endemic region, a compatible presentation (characteristically painless, progressive ulceration with undermined edges) is frequently diagnosed presumptively on clinical grounds.
• Laboratory confirmation is pursued to support the clinical assessment and guide any need for treatment modification.
• Polymerase chain reaction testing for the Mycobacterium ulcerans specific insertion sequence (IS2404), on a swab or tissue sample from the lesion, is the most sensitive and widely used confirmatory test.
• Acid fast staining and culture are supportive, generally less sensitive, alternative or adjunctive approaches. Culture requires prolonged incubation because the organism grows slowly.
• Histopathological examination of biopsy material shows extensive coagulative necrosis with a relative paucity of inflammatory cellular infiltrate, reflecting the local immunosuppressive effect of mycolactone. Clusters of acid fast bacilli are also seen.
• Histopathology supports the diagnosis particularly where other testing is unavailable or inconclusive.

• Combination antibiotic therapy is standard, current first line treatment: rifampicin 10 mg per kg once daily with clarithromycin 7.5 mg per kg twice daily, given for a total of eight weeks.
• This reflects a substantial shift from the historical, predominantly surgical approach toward an effective, well established medical strategy.
• Streptomycin combined with rifampicin is an established alternative regimen. Its use has declined because injectable administration and toxicity monitoring are disadvantages compared with the now preferred, fully oral rifampicin and clarithromycin combination.
• Surgical management remains an important adjunct for more advanced or extensive disease. It includes debridement of necrotic tissue and, for more extensive lesions, skin grafting to support wound closure and minimise scarring and contracture.
• The extent of surgery required has been substantially reduced by routine use of effective antibiotics. In many cases healing is achieved with more limited surgery than was historically required.
• Wound care is an essential supportive component throughout treatment. It includes regular dressing changes and monitoring for secondary bacterial infection.
• Physiotherapy maintains joint mobility and function, particularly for lesions affecting or adjacent to joints. Extensive tissue loss and scarring carry a significant risk of contracture if proactive functional management is not maintained.
• A paradoxical reaction is a recognised phenomenon in which the lesion appears to worsen clinically during or shortly after completing antibiotics. It reflects an immune reconstitution type inflammatory response as the local immunosuppressive effect of mycolactone resolves with bacterial killing.
• Recognise that this is a positive treatment response rather than treatment failure. It is generally managed conservatively with continued wound care, rather than antibiotic escalation or surgery.
• Careful clinical assessment is important to distinguish it from genuine secondary infection or treatment failure.
• Early recognition and treatment, ideally at the earliest, smallest lesion stage, substantially reduces tissue destruction, required treatment intensity, and functional and cosmetic morbidity.
• This underscores the importance of community awareness and early presentation in endemic regions.
• Ongoing rehabilitation support addresses any residual functional impairment or disfigurement after treatment of more advanced disease.