off leaving a painless ulcer. Buruli ulcers typically have "undermined edges", the ulcer being a few centimeters wider underneath the skin than the wound itself. In some people, the ulcer may heal on its own or remain small but linger unhealed for years. In others, it continues to grow wider and sometimes deeper, with skin at the margin dying and sloughing off. Large ulcers may extend deep into underlying tissue, causing bone infection and exposing muscle, tendon, and bone to the air. When ulcers extend into muscles and tendons, parts of these tissues can be replaced by scar tissue, immobilizing the body part and resulting in permanent disability. Exposed ulcers can be infected by other bacteria, causing the wound to become red, painful, and foul smelling. Symptoms are typically limited to those caused by the wound; the disease rarely affects other parts of the body. Buruli ulcers can appear anywhere on the body, but are typically on the limbs. Ulcers are most common on the lower limbs (roughly 62% of ulcers globally) and upper limbs (24%), but can also be found on the trunk (9%), head or neck (3%), or genitals (less than 1%). The World Health Organization classifies Buruli ulcer into three categories depending on the severity of its symptoms. Category I describes a single small ulcer that is less than . Category II describes a larger ulcer, up to , as well as plaques and broader swollen areas that have not yet opened into ulcers. Category III is for an ulcer larger than 15 centimeters, multiple ulcers, or ulcers that have spread to include particularly sensitive sites such as the eyes, bones, joints, or genitals. Cause Buruli ulcer is caused by infection of the skin with the bacterium Mycobacterium ulcerans. M. ulcerans is a mycobacterium, closely related to Mycobacterium marinum which infects aquatic animals and, rarely, humans. It is more distantly related to other slow-growing mycobacteria that infect humans, such as Mycobacterium tuberculosis, which causes tuberculosis, and Mycobacterium leprae, which causes leprosy. Buruli ulcer typically occurs near slow-moving or stagnant bodies of water, where M. ulcerans is found in aquatic insects, mollusks, fish, and the water itself. How M. ulcerans is transmitted to humans remains unclear, but somehow bacteria enter the skin and begin to grow. Ulceration is primarily caused by the bacterial toxin mycolactone. As the bacteria grow, they release mycolactone into the surrounding tissue. Mycolactone diffuses