Leprosy Treatment & Management

  • Author: Darvin Scott Smith, MD, MSc, DTM&H; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jul 6, 2011
 

Medical Care

In response to the increased incidence of dapsone resistance, the WHO introduced a multidrug regimen in 1981 that includes rifampicin, dapsone, and clofazimine. Some clinical studies have also shown that certain quinolones, minocycline, and azithromycin have activity against M leprae. The WHO recently recommended single-dose treatment with rifampin, minocycline, or ofloxacin in patients with paucibacillary leprosy who have a single skin lesion. However, the WHO still recommends the use of the long-term multidrug regimens whenever possible because they have been found to be more efficacious.

Table. Multidrug Therapy Plan Recommended by the WHO (Open Table in a new window)

Type of LeprosyDaily, Self-AdministeredMonthly SupervisedMonths of Treatment
PaucibacillaryDapsone 100 mgRifampicin 600 mg6-12
MultibacillaryDapsone 100 mg,



Clofazimine 50 mg



Rifampicin 600 mg,



Clofazimine 300 mg



24
PediatricDapsone 2 mg/kg,



Clofazimine 1 mg/kg



Rifampicin 10 mg/kg,



Clofazimine 6 mg/kg



Same as in adults

US regimens emphasize the use of rifampin, which is the most bactericidal drug used to treat leprosy. Although a single dose of 600 mg once monthly (the WHO standard) is considered bactericidal, treatment plans in the United States may include doses of 600 mg/day.

  • Paucibacillary leprosy should be treated for 6-12 months with dapsone 100 mg/day unsupervised plus rifampin 600 mg/month supervised. This regimen should be followed by treatment with dapsone as monotherapy for 3 years in patients with tuberculoid leprosy or 5 years in patients with borderline lepromatous leprosy.
  • Multibacillary leprosy should be treated for 24 months with dapsone 100 mg/day unsupervised, clofazimine 50 mg/day unsupervised, and rifampin 600 mg plus clofazimine 300 mg/month supervised.
  • Corticosteroids have been used to treat nerve damage associated with leprosy, but a recent review of 3 randomized controlled trials shows no significant long-term effect.[9] Prednisolone is believed to minimize pain and acute inflammation. The recommended initial dose is prednisolone 40 mg daily.
  • Observations of increasing resistance in patients treated for leprosy have been reported in Southeast Asia, notably in Vietnam.[10] The drug most commonly found to be resistant is dapsone, often in the context of prior exposure or treatment attempts with monotherapy. Although drug resistance is an ongoing concern, it is difficult to assess in this slow-growing organism. In a study of M leprae strains from South America, few of 230 strains subjected to molecular drug-susceptibility analysis were drug-resistant. Of the 230 strains, 3 were identified as clinically relapsing and were found to be resistant by genetic testing; 2 of the 3 were dapsone-resistant; and 1 was dapsone-resistant and rifampin-resistant using genetic testing for point mutation.[11]
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Surgical Care

  • The goals of surgical treatment in patients with leprosy are to prevent further deterioration, to improve motor function, and, in some cases, to improve sensation.
  • Preoperative requirements: First, a full sensory and motor appraisal with functional and occupational assessment must be completed to determine the extent of damage. Additionally, patients must have completed the multidrug therapy and should have negative skin smear results. The patient should not use steroids a few months before surgery, and acute neuritis should not be evident. Stiffness of hands and feet should be minimized with preoperative therapy.
  • Neural surgery
    • Attempts to restore autonomic function and sensation are rarely undertaken since little evidence shows that function is significantly regained. Draining of acute nerve abscesses and fascicular dissection can reduce the pressure on nerves and may improve sensation. In some cases, longitudinal epineurotomy may relieve some sensory loss. Considerable nerve function can be regained in the posterior tibial nerve with neurovascular decompression via release of the flexor retinaculum. Calcaneal bands can be slit to relieve distal compression of branches on the sole of the foot.
    • Nerve grafts may be of some benefit in patients with localized lesions. Neural surgery may also be indicated in patients with unremitting nerve pain.
  • Reconstruction and functional restoration[6]
    • In leprosy management, the goal of most surgical procedures is to remedy motor paralysis due to primary nerve impairment. Claw fingers and Z-thumbs caused by ulnar nerve paralysis are among the most common deformities. Clawed hands are repaired with arthrodesis or with a tendon transfer to 1 of 4 insertion sites on the finger: interosseus tendons, proximal phalanx, dorsal extensor expansion, or flexor sheath annular pulleys. The palmaris longus, flexor digitorum superficialis, extensor carpi radialis longus, and extensor indices are tendons that can be used for transfer. Tendon transfers are also used to repair abduction and opposition of the thumb, dorsiflexion of the foot, and flexion and extension of the metacarpophalangeal and proximal interphalangeal joints, respectively.
    • Contractures of the hand, such as the thumb web contracture, can be repaired with Z-plasty, and joint stability can be improved with tenodesis.
    • The constrictions caused by repetitive injury and healing in patients with leprosy can be treated with several methods. Possible treatment options include removal of the carpal tunnel roof, ulnar nerve transposition anteriorly, and epicondylectomy.
    • Procedures that limit hyperextension of the metacarpophalangeal joint or keep it in flexion are not indicated in the insensate hands of patients with leprosy, who suffer from continued weakness.
    • Amputation is a last resort and is reserved for cases of extremely diseased tissue.
  • Eye procedures: Loss of eyelid function may be treated with passing a strip from the temporalis muscle through the eyelid and connecting it to the inner canthus. Tarsorrhaphy may help narrow the opening of the eyelid, and canthoplasty reduces sagging of the eyelids.
  • Cosmetic surgery: After the disease is controlled medically, the following cosmetic procedures may also be considered:
    • Nasal reconstruction
    • Removal of excess skin
    • Replacement of eyebrows using transplants of scalp hair
    • Removal of breast tissue formation due to gynecomastia
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Consultations

Consultations may include an orthopedic surgeon, dermatologist, neurologist, and physical therapist, based on the needs of the individual patient.

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Contributor Information and Disclosures
Author

Darvin Scott Smith, MD, MSc, DTM&H  Adjunct Assistant Professor, Department of Microbiology and Immunology, Stanford University School of Medicine; Chief of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Kaiser Redwood City Hospital

Darvin Scott Smith, MD, MSc, DTM&H is a member of the following medical societies: American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International Society of Travel Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Tara Ramachandra  Stanford University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Fred A Lopez, MD  Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine

Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, and Louisiana State Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Charles V Sanders, MD  Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Baxter International and Johnson & Johnson Royalty Other

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References
  1. World Health Organization. Global leprosy situation, 2005. Wkly Epidemiol Rec. Aug 26 2005;80(34):289-95. [Medline].

  2. Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev. Apr 2006;19(2):338-81. [Medline]. [Full Text].

  3. Joyce MP, Scollard DM. Leprosy (Hansen's Disease). Conn's Current Therapy. 2004;100-105.

  4. Truman RW, Singh P, Sharma R, et al. Probable zoonotic leprosy in the southern United States. N Engl J Med. Apr 28 2011;364(17):1626-33. [Medline].

  5. Ustianowski AP, Lockwood DN. Leprosy: current diagnostic and treatment approaches. Curr Opin Infect Dis. Oct 2003;16(5):421-7. [Medline].

  6. Anderson GA. The surgical management of deformities of the hand in leprosy. J Bone Joint Surg Br. Mar 2006;88(3):290-4. [Medline].

  7. Walker SL, Lockwood DN. Leprosy. Clin Dermatol. Mar-Apr 2007;25(2):165-72. [Medline].

  8. Anderson H, Stryjewska B, Boyanton BL, et al. Hansen disease in the United States in the 21st century: a review of the literature. Arch Pathol Lab Med. Jun 2007;131(6):982-6. [Medline].

  9. [Best Evidence] Van Veen NH, Nicholls PG, Smith WC, Richardus JH. Corticosteroids for treating nerve damage in leprosy. Cochrane Database Syst Rev. Apr 18 2007;CD005491. [Medline].

  10. Kai M, Nguyen Phuc NH, et al. Analysis of Drug-Resistant Strains of Mycobacterium leprae in an Endemic Area of Vietnam. Clin Infect Dis. Mar 2011;52(5):e127-32.

  11. Singh P, Busso P, Paniz-Mondolfi A, et al. Molecular Drug Susceptibility Testing and Genotyping of Mycobacterium leprae Strains from South America. Antimicrob Agents Chemother. Jun 2011;55(6):2971-3. [Medline]. [Full Text].

  12. Bakker MI, Hatta M, Kwenang A, et al. Risk factors for developing leprosy--a population-based cohort study in Indonesia. Lepr Rev. Mar 2006;77(1):48-61. [Medline].

  13. Britton WJ, Lockwood DN. Leprosy. Lancet. Apr 10 2004;363(9416):1209-19. [Medline].

  14. Deps PD, Guedes BV, Bucker Filho J, Andreatta MK, Marcari RS, Rodrigues LC. Characteristics of known leprosy contact in a high endemic area in Brazil. Lepr Rev. Mar 2006;77(1):34-40. [Medline].

  15. Jacobson RR, Krahenbuhl JL, Yoder L. Overview of Leprosy. UpToDate. 2006.

  16. Leprosy. World Health Organization. Available at www.who.org.

  17. Moschella SL. An update on the diagnosis and treatment of leprosy. J Am Acad Dermatol. Sep 2004;51(3):417-26. [Medline].

  18. Rao PS, Sugamaran DS, Richard J, et al. Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy. Lepr Rev. Mar 2006;77(1):25-33. [Medline].

  19. Sridharan R, Lorenzo N, Narasimhan L. Leprosy. eMedicine. 2005.

  20. van Beers SM, Hatta M, Klatser PR. Patient contact is the major determinant in incident leprosy: implications for future control. Int J Lepr Other Mycobact Dis. Jun 1999;67(2):119-28. [Medline].

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Hands with Z-thumbs, clawing, contractures, and shortening of fingers due to repetitive injury and healing. Ho Chi Minh City, Vietnam. (Courtesy of D. Scott Smith, MD)
Patient with facial nerve palsy and contractures of the hand. Daloa, Ivory Coast. (Courtesy of D. Scott Smith, MD)
Chronic insensate patch due to leprosy infection. Ho Chi Minh City, Vietnam. (Courtesy of D. Scott Smith, MD)
Characteristic clawed hand deformity caused by ulnar involvement in leprosy. Daloa, Ivory Coast. (Courtesy of D. Scott Smith, MD)
Chronic nonhealing ulcer at the metatarsal head resulting from loss of sensation in the feet. Karigiri, Tamil Nadu, India. (Courtesy of Tara Ramachandra)
Multiple flat hypopigmented lesions on shoulder and neck, suggestive of multibacillary leprosy. Note ulceration of hypothenar area of hand, indicative of ulnar neuropathy. Redwood City, California, United States. (Courtesy of D. Scott Smith, MD)
Man with advanced deformities caused by unmanaged leprosy. Keratitis, loss of eyebrow, thickened skin, and typical hand impairments. Ho Chi Minh City, Vietnam. (Courtesy of D. Scott Smith, MD)
Histopathology of leprosy: Large numbers of acid-fast bacilli (in clusters) in histiocytes and within nerves. Fite-Faraco stain 500 X. (Courtesy of Tara Ramachandra and D. Scott Smith, MD)
Patient with multibacillary leprosy showing subsequent erythema nodosum leprosum reaction. Santa Clara, California. (Courtesy of D. Scott Smith, MD)
Patient with erythema nodosum leprosum type 2 reaction several weeks after initiation of drug therapy. This photograph was taken after tendon release. Redwood City, California. (Courtesy of D. Scott Smith, MD)
Increased pigmentation on the face due to clofazimine therapy. (Courtesy of D. Scott Smith, MD)
Table. Multidrug Therapy Plan Recommended by the WHO
Type of LeprosyDaily, Self-AdministeredMonthly SupervisedMonths of Treatment
PaucibacillaryDapsone 100 mgRifampicin 600 mg6-12
MultibacillaryDapsone 100 mg,



Clofazimine 50 mg



Rifampicin 600 mg,



Clofazimine 300 mg



24
PediatricDapsone 2 mg/kg,



Clofazimine 1 mg/kg



Rifampicin 10 mg/kg,



Clofazimine 6 mg/kg



Same as in adults
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