Buruli Ulcer 

  • Author: Aaron Z Hoover, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Apr 13, 2010
 

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]

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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]

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Epidemiology

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. 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.

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.

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Proceed to Clinical Presentation
 
 
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.

Specialty Editor Board

Franklin Flowers, MD  Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, 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.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster 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.

Paul Krusinski, MD  Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

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.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M 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, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The author and editors of eMedicine gratefully acknowledge the contributions of the following previous authors, Brian P. Green, DO, MS, PA-C, Sean T. Gunning, MD, and Mary K. Mather, MD, to the development and writing of this article. The author and editors of eMedicine would also like to thank Wayne M. Meyers, MD, for his clinical images from his article with Douglas S. Walsh, MD, in Transactions of the Royal Society of Tropical Medicine and Hygiene.[3] The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

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. [Best Evidence] Nienhuis WA, Stienstra Y, Thompson WA, et al. Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomised controlled trial. Lancet. Feb 20 2010;375(9715):664-72. [Medline].

  27. 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].

  28. 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].

  29. 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].

  30. 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].

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

  32. 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].

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

  34. 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.

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

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

  37. 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].

  38. 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].

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

 
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Buruli ulcer can extend to 15% of a person's skin surface and may destroy nerves and blood vessels. Metastatic bone lesions may develop.
An edematous Buruli ulcer in a 9-year-old Togolese girl. Courtesy of Wayne M. Meyers, MD.
Photo of Tongolese girl taken 5 years after the Buruli ulcer had been excised and repaired with autologous split-skin graft by G.B. Priuli, MD. Courtesy of Wayne M. Meyers, MD.
Table. Categories of Treatment
CategoryForm of DiseaseTreatmentPrimary AimSecondary Aimlevel of Health Care SystemDiagnosis
ISmall early lesion (eg, nodules, papules, plaques, ulcers < 5 cm in diameter)For papules and nodules, if immediate excision and suturing is possible, start antibiotics at least 24 hours before surgery and continue for 4 weeks. Otherwise, treat all lesions in this category with antibiotics for 8 weeks. Cure without surgery except for simple removal of dead tissueReduce or prevent recurrenceCommunity health centers and district hospitalsClinical and laboratory
IINonulcerative and ulcerative plaque and edematous forms



Large ulcerative lesions (>5 cm in diameter)



Lesions in the head and neck region, particularly the face



Treat with antibiotics for at least 4 weeks, then surgery (if necessary), followed by another 4 weeks of antibiotics.Reduce extent of the surgical excisionReduce or prevent recurrenceDistrict and tertiary hospitalsClinical and laboratory
IIIDisseminated/mixed forms (eg, osteitis, osteomyelitis, joint involvement)Treat with antibiotics for at least 1 week before surgery and continue for a total of 8 weeks.Reduce M ulcers infection and dissemination before and after surgeryReduce or prevent recurrence; reduce extent of surgical excisionDistrict and tertiary hospitalsClinical and laboratory
From " Provisional guidance on the role of specific antibiotics in the management of Mycobacterium ulcerans disease (Buruli ulcer). "[24]
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