eMedicine Specialties > Dermatology > Mycobacterial Infections

Buruli Ulcer

Author: Aaron Z Hoover, MD, Staff Dermatologist/Dermatopathologist, San Antonio Uniformed Services Health Education Consortium (SAUSHEC); Assistant Professor of Dermatology, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Mar 12, 2009

Introduction

Background

Buruli ulcer, also known as Bairnsdale ulcer, Daintree ulcer, Mossman ulcer, and Searl ulcer, is a chronic, indolent, necrotizing disease of the skin and soft tissue. Buruli ulcer is the third most common mycobacterial disease of immunocompetent hosts, after tuberculosis and leprosy, and is caused by toxin-producing  mycobacteria named Mycobacterium ulcerans.1 Buruli ulcer generally begins as a painless dermal papule or subcutaneous nodule, which, over a period of weeks to months, breaks down to form a necrotic ulcer with extensively undermined edges. Lesions heal with scarring, which is a significant source of morbidity.

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. Over the last 2 decades, a reemergence of cases has occurred, leading to the 1998 World Health Organization (WHO)2 Buruli Ulcer Initiative and the Fifty-Seventh World Health Assembly Resolution on Buruli Ulcer, which have stimulated ongoing research into diagnosis, pathogenesis, and effective treatment.3,4

Pathophysiology

M ulcerans are slow-growing mycobacteria that affect the skin and the mucous membranes. The organism produces a soluble polyketide toxin called mycolactone. Mycolactone has both immunosuppressive properties and cytotoxic properties, which explains the lack of host symptoms, such as fever, malaise, or adenopathy.5,6 Mycolactone is responsible for the extensive tissue necrosis seen in Buruli ulcers.

Mycolactone has been shown to induce apoptosis without inducing inflammation.7 Thus, M ulcerans does not cause the same degree of inflammation associated with other mycobacterial infections, such as Mycobacterium leprae and Mycobacterium tuberculosis.

Genetic susceptibility is a possibility, associated with the SCLC11A1 (NRAMP1) D543 polymorphism.8

Frequency

United States

Three cases have been diagnosed in the United States, all of which originated from outside the United States.

International

Buruli ulcers have been reported in more than 30 countries. The largest number of endemic cases occur in countries in central and western Africa, such as Zaire, Congo, Cameroon, Nigeria, Benin,9 Ghana,10 Togo,11 Liberia, and the Ivory Coast. Other involved geographic areas include Australia, Southeast Asia, and sporadic cases in Central America and South America. Subtropical and swampy terrain are major endemic foci for M ulcerans.

Mortality/Morbidity

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.


<BR><BR>Buruli ulcer can extend to 15% of a perso...



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

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<BR><BR>Buruli ulcer can extend to 15% of a perso...



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


The infection may extend deep, exposing fascia, muscle, and bone. More than half the affected individuals are left with a functional limitation. The scarring can be disfiguring and can have a significant emotional impact on patients. Treatment involves long hospital stays, antibiotic regimens, and surgical procedures, which are resources often limited in endemic areas.

Race

No specific racial predilection is known.

Sex

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

Age

Cases most commonly occur in children ages 5-15 years, except in Australia, where Buruli ulcer is more prevalent in adults older than 50 years; however, Buruli ulcer may affect any age group.

Clinical

History

  • The incubation period ranges from a few weeks to months.
  • Lesions usually begin as a single, painless, occasionally pruritic, dermal papule or subcutaneous nodule.
  • Suppuration and ulceration occur within 1-2 months.

Physical

  • Approximately 90% of lesions occur on the limbs, with 60% occurring on the lower limbs.
  • In the preulcerative stage, Buruli ulcer manifests initially as firm, nontender, subcutaneous nodules 1-2 cm in diameter. Less common presentations include a dermal papule, indurated plaque, or a more aggressive edematous variant that rapidly causes diffuse swelling, which can involve an entire extremity and results in the formation of a very large ulcer.
  • The ulcerative stage occurs days to weeks later with the formation of an ulcer with undermined edges. The necrosis along the panniculus 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. Ulcerations are generally painless unless complicated by secondary infection. The Buruli ulcers may destroy nerves, appendages, and blood vessels and may invade bone. A few studies have shown relatively high frequencies of bone involvement (15% of patients). Metastatic lesions may occur in skin, soft tissue, or bone via spread through the vasculature or lymphatics.
  • Healing is a slow process that often results in cosmetically disfiguring scars and functional disabilities.

Causes

  • M ulcerans are slow-growing mycobacteria and are the causative agent of Buruli ulcer.
  • M ulcerans is an environmental pathogen that has been isolated from biofilms and small aquatic animals of slow-moving or stagnant bodies of water.12,13,14,15 Although the exact mode of transmission is unknown, M ulcerans most likely causes infection through contamination of a traumatic wound.16 A role in transmission via the bites of Australian salt marsh mosquitoes and African biting water insects (Naucoridae and Belostomatidae) has been suggested.17   Human-to-human transmission has rarely been reported.
  • A plasmid-encoded polyketide toxin called mycolactone is responsible for the extensive destruction and suppressed host response in Buruli ulcers. A total of 4 variants have been identified. Mycolactones A and B are the more virulent variates and are found in Africa. Mycolatone C is found in Australia, and Mycolatone D is found in Asia.

More on Buruli Ulcer

Overview: Buruli Ulcer
Differential Diagnoses & Workup: Buruli Ulcer
Treatment & Medication: Buruli Ulcer
Follow-up: Buruli Ulcer
Multimedia: Buruli Ulcer
References
Further Reading
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References

  1. Sizaire V, Nackers F, Comte E, Portaels F. Mycobacterium ulcerans infection: control, diagnosis, and treatment. Lancet Infect Dis. May 2006;6(5):288-96. [Medline].

  2. World Health Organization. Buruli ulcer disease (Mycobacterium ulcerans infection). World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs199/en/. Accessed December 3, 2008.

  3. Walsh DS, Portaels F, Meyers WM. Buruli ulcer (Mycobacterium ulcerans infection). Trans R Soc Trop Med Hyg. Oct 2008;102(10):969-78. [Medline].

  4. Wansbrough-Jones M, Phillips R. Buruli ulcer: emerging from obscurity. Lancet. Jun 3 2006;367(9525):1849-58. [Medline].

  5. George KM, Chatterjee D, Gunawardana G, et al. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science. Feb 5 1999;283(5403):854-7. [Medline].

  6. Pimsler M, Sponsler TA, Meyers WM. Immunosuppressive properties of the soluble toxin from Mycobacterium ulcerans. J Infect Dis. Mar 1988;157(3):577-80. [Medline].

  7. Walsh DS, Meyers WM, Portaels F, et al. High rates of apoptosis in human Mycobacterium ulcerans culture-positive buruli ulcer skin lesions. Am J Trop Med Hyg. Aug 2005;73(2):410-5. [Medline].

  8. Stienstra Y, van der Werf TS, Oosterom E, et al. Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism. Genes Immun. Apr 2006;7(3):185-9. [Medline].

  9. Guedenom A, Zinsou C, Josse R, et al. Traditional treatment of Buruli ulcer in Benin. Arch Dermatol. Jun 1995;131(6):741-2. [Medline].

  10. Aiga H, Amano T, Cairncross S, Adomako J, Nanas OK, Coleman S. Assessing water-related risk factors for Buruli ulcer: a case-control study in Ghana. Am J Trop Med Hyg. Oct 2004;71(4):387-92. [Medline].

  11. Meyers WM, Tignokpa N, Priuli GB, Portaels F. Mycobacterium ulcerans infection (Buruli ulcer): first reported patients in Togo. Br J Dermatol. Jun 1996;134(6):1116-21. [Medline].

  12. Eddyani M, Ofori-Adjei D, Teugels G, et al. Potential role for fish in transmission of Mycobacterium ulcerans disease (Buruli ulcer): an environmental study. Appl Environ Microbiol. Sep 2004;70(9):5679-81. [Medline].

  13. Marsollier L, Severin T, Aubry J, et al. Aquatic snails, passive hosts of Mycobacterium ulcerans. Appl Environ Microbiol. Oct 2004;70(10):6296-8. [Medline].

  14. Marsollier L, Stinear T, Aubry J, et al. Aquatic plants stimulate the growth of and biofilm formation by Mycobacterium ulcerans in axenic culture and harbor these bacteria in the environment. Appl Environ Microbiol. Feb 2004;70(2):1097-103. [Medline].

  15. Raghunathan PL, Whitney EA, et al. Risk factors for Buruli ulcer disease (Mycobacterium ulcerans Infection): results from a case-control study in Ghana. Clin Infect Dis. May 15 2005;40(10):1445-53. [Medline].

  16. Meyers WM, Shelly WM, Connor DH, Meyers EK. Human Mycobacterium ulcerans infections developing at sites of trauma to skin. Am J Trop Med Hyg. Sep 1974;23(5):919-23. [Medline].

  17. Johnson PD, Azuolas J, Lavender CJ, et al. Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, southeastern Australia. Emerg Infect Dis. Nov 2007;13(11):1653-60. [Medline].

  18. Phillips R, Horsfield C, Kuijper S, et al. Sensitivity of PCR targeting the IS2404 insertion sequence of Mycobacterium ulcerans in an Assay using punch biopsy specimens for diagnosis of Buruli ulcer. J Clin Microbiol. Aug 2005;43(8):3650-6. [Medline].

  19. Rondini S, Mensah-Quainoo E, Junghanss T, Pluschke G. What does detection of Mycobacterium ulcerans DNA in the margin of an excised Buruli ulcer lesion tell us?. J Clin Microbiol. Nov 2006;44(11):4273-5. [Medline].

  20. Siegmund V, Adjei O, Nitschke J, et al. Dry reagent-based polymerase chain reaction compared with other laboratory methods available for the diagnosis of Buruli ulcer disease. Clin Infect Dis. Jul 1 2007;45(1):68-75. [Medline].

  21. Leigheb G, Cammarota T, Zavattaro E, et al. Ultrasonography for the monitoring of subcutaneous damage in Mycobacterium ulcerans infection (Buruli ulcer). Ultrasound Med Biol. Oct 2008;34(10):1554-63. [Medline].

  22. Chauty A, Ardant MF, Adeye A, et al. Promising clinical efficacy of streptomycin-rifampin combination for treatment of buruli ulcer (Mycobacterium ulcerans disease). Antimicrob Agents Chemother. Nov 2007;51(11):4029-35. [Medline].

  23. Etuaful S, Carbonnelle B, Grosset J, et al. Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans. Antimicrob Agents Chemother. Aug 2005;49(8):3182-6. [Medline].

  24. World Health Organization. Provisional guidance on the role of specific antibiotics in the management of Mycobacterium ulcerans disease (Buruli ulcer). World Health Organization. Available at http://www.who.int/buruli/information/antibiotics/en/. Accessed December 3, 2008.

  25. Johnson PD, Hayman JA, Quek TY, et al. Consensus recommendations for the diagnosis, treatment and control of Mycobacterium ulcerans infection (Bairnsdale or Buruli ulcer) in Victoria, Australia. Med J Aust. Jan 15 2007;186(2):64-8. [Medline].

  26. Meyers WM, Shelly WM, Connor DH. Heat treatment of Mycobacterium ulcerans infections without surgical excision. Am J Trop Med Hyg. Sep 1974;23(5):924-9. [Medline].

  27. Krieg RE, Wolcott JH, Confer A. Treatment of Mycobacterium ulcerans infection by hyperbaric oxygenation. Aviat Space Environ Med. Oct 1975;46(10):1241-5. [Medline].

  28. Phillips R, Adjei O, Lucas S, Benjamin N, Wansbrough-Jones M. Pilot randomized double-blind trial of treatment of Mycobacterium ulcerans disease (Buruli ulcer) with topical nitrogen oxides. Antimicrob Agents Chemother. Aug 2004;48(8):2866-70. [Medline].

  29. Nackers F, Dramaix M, Johnson RC, et al. BCG vaccine effectiveness against Buruli ulcer: a case-control study in Benin. Am J Trop Med Hyg. Oct 2006;75(4):768-74. [Medline].

  30. van der Werf TS, Stienstra Y, Johnson RC, et al. Mycobacterium ulcerans disease. Bull World Health Organ. Oct 2005;83(10):785-91. [Medline].

  31. Bretzel G, Siegmund V, Racz P, et al. Post-surgical assessment of excised tissue from patients with Buruli ulcer disease: progression of infection in macroscopically healthy tissue. Trop Med Int Health. Nov 2005;10(11):1199-206. [Medline].

  32. Minutilli E, Orefici G, Pardini M, et al. Squamous cell carcinoma secondary to buruli ulcer. Dermatol Surg. Jul 2007;33(7):872-5. [Medline].

  33. Connor DH, Meyers WM, Kreig RE. Infection by Mycobacterium ulcerans. In: Binford CH, Connor DH, eds. Pathology of Tropical and Extraordinary Diseases. Washington, DC: Armed Forces Institute of Pathology; 1976:226-35.

  34. Health Section of the Secretariat of the League of Nations. Buruli ulcer disease. Wkly Epidemiol Rec. May 14 2004;79(20):194-9. [Medline].

  35. Meyers WM. Atypical mycobacteria skin infections. In: Strickland GT, ed. Hunter's Tropical Medicine. Philadelphia, Pa: WB Saunders; 1991:495-6.

  36. Prevot G, Bourreau E, Pascalis H, et al. Differential production of systemic and intralesional gamma interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease. Infect Immun. Feb 2004;72(2):958-65. [Medline].

  37. Stienstra Y, van der Werf TS, van der Graaf WT, et al. Buruli ulcer and schistosomiasis: no association found. Am J Trop Med Hyg. Sep 2004;71(3):318-21. [Medline].

  38. Wagner D, Young LS. Nontuberculous mycobacterial infections: a clinical review. Infection. Oct 2004;32(5):257-70. [Medline].

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Further Reading

The article by Walsh et al in Transactions of the Royal Society of Tropical Medicine and Hygiene is an excellent review of Buruli ulcers. 3

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Keywords

Buruli ulcer, Mycobacterium ulcerans, M ulcerans, Bairnsdale ulcer, Daintree ulcer, Mossman ulcer, Searl ulcer

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Contributor Information and Disclosures

Author

Aaron Z Hoover, MD, Staff Dermatologist/Dermatopathologist, San Antonio Uniformed Services Health Education Consortium (SAUSHEC); Assistant Professor of Dermatology, Uniformed Services University of the Health Sciences
Aaron Z Hoover, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Christian Medical & Dental Society, and International Society of Dermatopathology
Disclosure: Nothing to disclose.

Medical Editor

Franklin Flowers, MD, Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, University of Florida College of Medicine
Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont
Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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