Buruli Ulcer

Updated: Feb 06, 2017
  • Author: Shannon C Brown, MD; Chief Editor: William D James, MD  more...
  • Print
Overview

Background

Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic, debilitating, necrotizing disease of the skin and soft tissue. Buruli ulcer is an emerging infectious disease and is the third most common mycobacterial disease of the immunocompetent host, after tuberculosis and leprosy. [1] Although it has been reported in over 33 countries around the world, the greatest burden of disease is in the tropical regions of West and Central Africa, Australia, and Japan. [2] It primarily affects children aged 5-15 years. [2] Buruli ulcers generally begin as a painless dermal papule or subcutaneous edematous nodule, which, over a period of weeks to months, breaks down to form an extensive necrotic ulcer with undermined edges. Treatment includes a prolonged course of antibiotics and surgical debridement. Early identification and treatment are key, as lesions heal with scarring that can be a significant source of morbidity. Other names for this entity include Bairnsdale ulcer, Daintree ulcer, Mossman ulcer, and Searl ulcer. Note the image below.

Buruli ulcer can extend to 15% of a person's skin Buruli ulcer can extend to 15% of a person's skin surface and may destroy nerves and blood vessels. Metastatic bone lesions may develop.

Buruli ulcer was first described by Sir Albert Cook in patients from Buruli County in Uganda, and the causative organism was isolated in 1948 by MacCallum in the Bairnsdale region of Victoria, Australia. A reemergence of cases led the 1998 World Health Organization (WHO) to reclassify Buruli ulcer as a "neglected emerging infectious disease," which has stimulated ongoing research into diagnosis, pathogenesis, and effective treatment. [3, 4, 5]

Next:

Pathophysiology

M ulcerans are slow-growing mycobacteria that produce a soluble polyketide exotoxin called mycolactone, which can diffuse extensively in the subcutaneous tissue. Because mycolactone has both immunosuppressive properties and cytotoxic properties, dramatic tissue destruction occurs without inducing inflammation or systemic symptoms, such as fever, malaise, or adenopathy. [6, 7, 8, 9, 10] Mycolactone was first identified in 1999. Research has revealed the mechanisms of action of mycolactone, as described below.

Molecular targets

Mycolactone targets scaffolding proteins, such as the Wiskott-Aldrich syndrome protein (WASP), [11] which controls actin dynamics and leads to a loss of cellular detachments and cell death. [12]

Mycolactone also inhibits the function of the Sec61 translocation, which is responsible for protein translocation into the endoplasmic reticulum. This affects 30-50% of mammalian proteins, including circulating inflammatory mediators and proteins involved in lipid metabolism, coagulation, and tissue remodeling. [13] Therefore, patients with M ulcerans infections have global and chronic defects in protein metabolism. This is evident by reduced levels of total serum proteins and blood urea nitrogen, without the presence of malnutrition, kidney impairment, or liver impairment. [13]

Buruli ulcers are traditionally thought to be painless ulcers. Research has shown that the hypoalgesic effect occurs via activation of the angiotensin II type 2 receptor (AT2R), leading to neurite degeneration and cell death. [14] Another prominent feature of Buruli ulcers is extensive coagulative necrosis caused by mycolactone.

Ogbechi et al showed that mycolactone decreased thrombomodulin expression on the surface of human dermal microvascular endothelial cells, thereby impairing the activation of protein C. This study also showed that fibrin deposition is a prominent feature of these ulcers and the tissue necrosis could be caused by fibrin-driven ischemia. [15]

Genetic susceptibility

Genetic susceptibility may be associated with the SCLC11A1 (NRAMP1) D543 polymorphism. [16]

Previous
Next:

Epidemiology

US frequency

According to the World Health Organization (WHO), as of 2015, there have been no cases of confirmed Buruli ulcers originating in the United States. [3]

International frequency

Approximately 6000 cases are reported annually around the world, especially from rural Africa. [3]

Buruli ulcers have been reported in 33 countries. The largest number of endemic cases occur in countries in central and western Africa, such as Côte d'Ivoire, Benin, Ghana, Democratic Republic of the Congo, Cameroon, Nigeria, Togo, and Liberia. Other involved geographic areas include Australia, Papa New Guinea, Japan, and sporadic cases in Central and South America. Subtropical and swampy terrain are major endemic foci for M ulcerans.

Race

No specific racial predilection is known.

Sex

No differences exist in the rates of infection among males and females.

Age

Buruli ulcer may affect any age group, but most cases occur in children ages 5-15 years, except in Australia, where Buruli ulcer is more prevalent in adults older than 50 years. [17]

Previous
Next:

Prognosis

Most patients have complete healing, with or without significant scarring or impairment. Even with medical and surgical care, patients often require hospitalizations averaging 3 months. The best prognosis occurs when treatment is instituted as early as possible before significant tissue destruction can occur. Without medical care, more than half the affected individuals are left with a functional limitation. The scarring can be disfiguring and can have a significant emotional and socioeconomic impact on patients. Treatment involves long hospital stays (average of 3 months), antibiotic regimens, and surgical procedures, which are resources often limited in endemic areas. [18]

Buruli ulcer has a low mortality rate; however, it is a significant source of morbidity and socioeconomic burden. Skin and soft-tissue necrosis can be extensive, involving as much as 15% of the patient's skin surface and may extend deep, exposing fascia, muscle, and bone.

When Buruli ulcers are identified early and treated appropriately, the prognosis is good. Klis et al found that 85% of patients who presented with small lesions and who received 8 weeks of antibiotics indicated no effect, or only a small effect, of the disease on their current life at long-term follow up visits. [19] The median score on the Dermatology Life Quality Index was 0 (range, 0-4), indicating a good quality of life. [19] These results highlight the importance of early identification and treatment, in stark contrast with the debilitating contracted scars that result if these ulcers are not treated in a timely manner.

The majority of the systemic complications from Buruli ulcers are from the toxicities of long-term antibiotic use. See Treatment/Complications section.

Elderly patients have a tendency towards more severe disease and increased complications from treatment. [17]

 

Previous