Buruli Ulcer Treatment & Management

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

Medical Care

The medical management of Buruli ulcers is an active area of research to determine the most effective combination and duration of treatment with antimicrobials. Treatment has been shown to promote healing of smaller lesions and as an adjunct to surgical management to decrease recurrence. The best outcomes occur when treatment is initiated in smaller lesions (< 5 cm).

In 2004, the WHO recommended a treatment protocol that divided lesions into 3 categories. The WHO recommends that all categories receive a course of rifampicin and streptomycin. Recurrence rates after antibiotic treatment are reported to be 2-3%.[22, 23]

Table. Categories of Treatment (Open Table in a new window)

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]

In 2007, the Australian Victorian Department of Human Services recommended the combination of rifampicin and clarithromycin or ciprofloxacin or moxifloxacin for 3 months.[25] In severe disease, oral rifampicin with intravenous amikacin is the treatment of choice. Oral medications should be used for 12 weeks, and intravenous amikacin should be used for 4 weeks.

Nienhuis et al compared the efficacy of 2 antibiotic regimens for Mycobacterium ulcerans infection. In Ghana, patients aged 5 years or older were randomly assigned to receive streptomycin (15 mg/kg IM qd) plus rifampicin (10 mg/kg PO qd) for 8 weeks (n = 76) or streptomycin and rifampin for 4 weeks followed by rifampin and clarithromycin (7.5 mg/kg PO qd) for 4 weeks (n = 75). No significant difference was observed for each treatment regimen (healed lesions at 1 y were 96% for 8-wk streptomycin vs 91% for 4-wk streptomycin); however, the number of streptomycin injections was able to be reduced by switching to oral clarithromycin after 4 weeks.[26]

Hyperthermia with a 40°C water bath, such as a circulating water jacket, has shown some success.[27] The use of hyperbaric oxygen has also been reported as effective in a small number of patients.[28] One study (n = 12) found a significant decrease in the size of ulcers with the use of sodium nitrite and citric acid monohydrate creams topically. The decrease was most significant in the first 3 weeks.[29] Studies of the effectiveness of the BCG vaccine against M ulcerans have been variable. The BCG vaccine may provide some protection against the onset of disease, although this effect does not last past a year.[30, 31] Individuals who were previously immunized were less likely to have ulcers that cause osteomyelitis.

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Surgical Care

Excision was the treatment of choice in the past but now more likely serves as an adjunct to antibiotic treatment. The recurrence rate after surgery alone is 6-30%, depending on the extent of the lesion. Devitalized tissue should be debrided on all wounds to enhance healing. Subcutaneous nodules or small ulcerations may be excised en bloc with primary closure. Large lesions are often excised with skin graft closure. Note the images below. Use of PCR to evaluate surgical margins may reduce recurrences.[32]

An edematous Buruli ulcer in a 9-year-old TogoleseAn 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 BuPhoto 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.
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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.

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

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  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].

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  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].

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  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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