Buruli Ulcer Clinical Presentation

Updated: Feb 06, 2017
  • Author: Shannon C Brown, MD; Chief Editor: William D James, MD  more...
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Owing to the long incubation period of Mycobacterium ulcerans, ranging from 1-9 months, with a mean of 4.5 months, most patients do not recall an inciting event. [20] Lesions usually begin as a single, painless, occasionally pruritic, dermal papule or subcutaneous nodule. Because the initial lesion is painless, many patients do not seek immediate medical attention. Suppuration and necrotic ulceration occurs within 1-2 months. Otherwise, the patients are generally healthy. Systemic symptoms such as fever or lymphadenopathy are rare owing to the immunosuppressive effects of mycolactone.

The peak incidence of cases is in March, typically in swampy areas, suggesting an association with rainy seasons in West Africa. [21]



Physical Examination

Classically, Buruli ulcers are considered an expanding ulceration on the lower extremity, although they can occur anywhere. Approximately 90% of lesions occur on the limbs, with 60% occurring on the lower extremities. Patients present with nonulcerative lesions in 0-30% of cases and with ulcerative lesions in 70-100% of cases. [37] See the image below.

Well-circumscribed ulceration with sharp, undermin Well-circumscribed ulceration with sharp, undermined borders on the lower leg. Courtesy of Ronald E Grimwood, Jr, MD, Baylor Scott and White Health.

In the preulcerative stage, Buruli ulcer manifests initially as firm, nontender, subcutaneous nodule 1-2 cm in diameter. Less common presentations include a dermal papule or indurated plaque. A more aggressive edematous variant is frequently seen in Australia. The edematous variant causes a rapid onset of diffuse swelling, which can involve an entire extremity and evolves into an extensive ulcer. This is frequently misdiagnosed as cellulitis. [38]

The ulcerative stage occurs days to weeks later. The skin covering the plaque or nodule slowly sloughs, leaving an extensive necrotic ulcer with undermined edges. Subcutaneous necrosis may extend several centimeters beyond the edge of the ulcer; therefore, the lesion appears smaller than its actual size. Characteristic lesions have a scalloped border and a sloughing, necrotic base. The ulcers may appear yellow or green and have a characteristic smell. Pain and local lymphadenopathy suggest secondary infection. [39]

Buruli ulcers may destroy nerves, appendages, and blood vessels and may invade bone. Metastatic lesions may occur in the skin, soft tissue, or bone via spread through the vasculature or lymphatics. Approximately 33% of patients present with underlying osteitis, osteomyelitis, or joint involvement. [3] Interestingly, one fourth of the patients with M ulcerans osteomyelitis have no apparent history of cutaneous Buruli ulcer. [40] . Half of these patients have crippling sequelae. [40]

Healing is a slow process and may result in cosmetically disfiguring scars and functional disabilities if treatment is delayed.



M ulcerans are slow-growing mycobacteria and are the causative agent of Buruli ulcers. The optimal temperature for growth is 30-32°C. This temperature is slightly below that of core body temperature and may explain some of the predisposition for lesions on the extremities and lack of visceral involvement. M ulcerans is sensitive to temperatures above 37°C, which has led to ongoing clinical trials using local heat application devices for treatment. [22]

M ulcerans is an environmental pathogen that has been isolated from biofilms and small aquatic animals of slow-moving or stagnant bodies of water. [23, 24, 25, 26] Although the exact mode of transmission is unknown, M ulcerans most likely causes infection through contamination of a traumatic wound. The absence of protective equipment during agricultural activities is a well-documented risk factor. [27] Proper wound hygiene has been shown to decrease infection rates. [28, 29, 30]

Because of its fragility and sensitivity to direct sunlight, M ulcerans likely persists within a protective host, although no hosts have been identified to date. [27] Transmission via the bites of Australian salt marsh mosquitoes with possums serving as the reservoir is supported by scientific evidence, but a mammalian reservoir has not been identified in other areas of the world. [28, 31, 32, 33] African biting water insects (Naucoridae, Belostomatidae, and Acanthamoeba species) have been implicated in the transmission of M ulcerans in ongoing research. [34, 33] Human-to-human transmission has rarely been reported. There is not an increased risk of infection associated with living with an infected family member. [28] In 2010, investigation of a familial outbreak of Buruli ulcers in Japan revealed matching insertion sequence 2404 in the infected wounds and crayfish found near the family's house. Given the location of the ulcers, direct inoculation was deemed unlikely. This supports the evidence that aquatic environments act as a reservoir for M ulcerans. [35]

A plasmid-encoded polyketide toxin termed mycolactone is responsible for the extensive destruction and suppressed host response in Buruli ulcers. Four variants have been identified. Mycolactone A and B are the more virulent variants and are found in Africa. Mycolactone C is found in Australia, and mycolactone D is found in Asia. [36] For more information, see Overview/Pathophysiology.