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Leprosy Workup

  • Author: Darvin Scott Smith, MD, MSc, DTM&H; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: May 09, 2016
 

Laboratory Studies

The WHO case definition of leprosy is M leprae infection in an individual who has not completed a course of treatment and has one or more of the following:

  • Hypopigmented or reddish skin lesions with loss of sensation
  • Involvement of the peripheral nerves as demonstrated by their thickening and associated loss of sensation
  • Skin smear positive for acid-fast bacilli

Laboratory studies include the following:

  • Skin biopsy, nasal smears, or both are used to assess for acid-fast bacilli using Fite stain. Biopsies should be full dermal thickness taken from an edge of the lesion that appears most active.[13]
  • Serologic assays can be used to detect phenolic glycolipid-1 (specific for M leprae) and lipoarabinomannan (commonly seen in mycobacteria).[13]
  • Molecular probes detect 40-50% of cases missed on prior histologic evaluation. Since probes require a minimum amount of genetic material (ie, 104 DNA copies), they can fail to identify paucibacillary leprosy.

Laboratory tests related to drug treatment follow-up include the following:

  • CBC count
  • Creatinine level
  • Liver function tests
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Other Tests

Immunologic tests include the following:

  • Polymerase chain reaction (PCR): PCR and recombinant DNA technology have allowed for the development of gene probes with M leprae–specific sequences. This technology can be used to identify the mycobacterium in biopsy samples, skin and nasal smears, and blood and tissue sections.[14]
  • Phenolic glycolipid-1: This is a specific serologic test based on the detection of antibodies to phenolic glycolipid-1. This test yields a sensitivity of 95% for the detection of lepromatous leprosy but only 30% for tuberculoid leprosy.
  • Lymphocyte migration inhibition test (LMIT): As determined by a lymphocyte transformation and LMIT, cell-mediated immunity to M leprae is absent in patients with lepromatous leprosy but present in those with tuberculoid leprosy.
  • Lepromin skin test (not available in the United States): Although not diagnostic of exposure to or infection with M leprae, this test assesses a patient's ability to mount a granulomatous response against a skin injection of killed M leprae. Patients with tuberculoid leprosy or borderline lepromatous leprosy typically have a positive response (>5 mm). Patients with lepromatous leprosy typically have no response.
  • Contact or family screening for history of leprosy
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Procedures

Skin biopsy samples stained with hematoxylin-eosin and Fite-Faraco are the primary basis for laboratory diagnosis and categorization. A full-thickness skin biopsy sample should be taken from an advancing border of an active lesion and should include dermis and epidermis. Skin smears that demonstrate acid-fast bacilli strongly suggest a diagnosis of leprosy, but the bacilli may not be demonstrable in tuberculoid (paucibacillary) leprosy.

A nerve biopsy can be beneficial in ruling out diseases such as hereditary neuropathies or polyarteritis nodosa. Nerve biopsies may also help identify abnormalities in patients with subclinical leprosy and may be the only way to definitively diagnose completely neuropathic forms of leprosy. If a nerve biopsy is needed to confirm diagnosis, a purely sensory nerve (eg, sural or radial cutaneous nerve) should be used. This procedure is rarely necessary.[12]

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Histologic Findings

Findings vary but can include dermatitis, giant cells, infiltration of nerve bundles with mononuclear cells, and granulomas. Lepromatous lesions generally contain numerous acid-fast bacilli and fat-laden macrophages with a paucity of lymphocytes. Histopathology of leprosy is seen in the image below.

Histopathology of leprosy: Large numbers of acid-fHistopathology 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.

In contrast, tuberculoid lesions contain few-to-no acid-fast bacilli but manifest granulomatous changes with epithelial cells and lymphocytes. The immunopathologic spectrum of leprosy has been delineated in the Neurologic Manifestations of Leprosy topic in Medscape Reference's Neurology volume.

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Staging

Leprosy is staged or graded based on microscopy findings to classify cases as paucibacillary or multibacillary so that duration and type of drug therapy can be determined.

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Contributor Information and Disclosures
Author

Darvin Scott Smith, MD, MSc, DTM&H Adjunct Associate Clinical 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, International Society of Travel Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Emily Anderson Kelly Stanford University

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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

Disclosure: Received royalty from Baxter International for other.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

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, Louisiana State Medical Society

Disclosure: Nothing to disclose.

Shwetha Ravindranath Katta, MD JJM Medical College, Davangere, India

Disclosure: Nothing to disclose.

Acknowledgements

Tara Ramachandra, MD Stanford University School of Medicine

Disclosure: Nothing to disclose.

References
  1. Reibel F, Cambau E, Aubry A. Update on the epidemiology, diagnosis, and treatment of leprosy. Médecine et Maladies Infectieuses. 2015 Sept 02. Volume 45, Issue 9:383–393.

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

  3. Schreuder PAM, Noto S, Richardus JH. Epidemiologic trends of leprosy for the 21st century. Clinics in Dermatology. 2015 Nov 04. Volume 34, Issue 1:24-31.

  4. The World Health Organization. Diagnosis of Leprosy. Leprosy Elimination. Available at http://www.who.int/lep/diagnosis/en/. Accessed: April 15, 2016.

  5. U.S. Department of Health and Human Services. National Hansen's Disease (Leprosy) Program. Health Resources and Services Administration. Available at http://www.hrsa.gov/hansensdisease/. Accessed: March 23, 2016.

  6. Fred F. Ferri. Leprosy. Ferri's Clinical Advisor 2015: 5 books in 1. Philadelphia, PA: Elsevier/Mosby; 2015. 687.e4-687.e5.

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

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

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

  11. The World Health Organization. Transmission of Leprosy. Leprosy Elimination. Available at http://www.who.int/lep/transmission/en/. Accessed: April 15, 2016.

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

  13. 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. 2007 Jun. 131(6):982-6. [Medline].

  14. Martinez AN, Talhari C, Moraes MO, Talhari S. PCR-based techniques for leprosy diagnosis: from the laboratory to the clinic. PLoS Negl Trop Dis. 2014 Apr. 8 (4):e2655. [Medline].

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

  17. 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.

  18. 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. 2011 Jun. 55(6):2971-3. [Medline]. [Full Text].

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

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

  21. 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. 2006 Mar. 77(1):34-40. [Medline].

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

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

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

  25. National Hansen's Disease (Leprosy) Program. U.S. Department of Health and Human Services. Available at http://www.hrsa.gov/hansensdisease/index.html. Accessed: July 21, 2014.

  26. 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. 2006 Mar. 77(1):25-33. [Medline].

  27. Sridharan R, Lorenzo N, Narasimhan L. Leprosy. Medscape Reference. 2005.

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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.
WHO Multidrug Therapy Regimens. Courtesy of WHO, Leprosy Elimination, http://www.who.int/lep/mdt/en/, accessed April 15, 2016.
Leprosy prevalence rates, 2014. Courtesy of WHO, Leprosy: Global situation, http://www.who.int/lep/situation/en/, accessed April 28, 2016.
Table 1. Multidrug Therapy Plan Recommended by the WHO
Type of LeprosyDaily, Self-AdministeredMonthly SupervisedMonths of Treatment
PaucibacillaryDapsone 100 mgRifampicin 600 mg6
Single-lesion paucibacillaryRifampicin 600 mg,



Ofloxacin 400 mg,



Minocycline 100 mg



N/ASingle dose
MultibacillaryDapsone 100 mg,



Clofazimine 50 mg



Rifampicin 600 mg,



Clofazimine 300 mg 



12
PediatricDapsone 2 mg/kg,



Clofazimine 1 mg/kg



Rifampicin 10 mg/kg,



Clofazimine 6 mg/kg



Same as in adults
Table 2. US Recommendations for Multidrug Therapy[15]
Type of LeprosyDaily, Self-AdministeredMonthly SupervisedMonths of Treatment
PaucibacillaryDapsone 100 mg,



Rifampicin 600 mg



N/A12
Single-lesion paucibacillaryDapsone 100 mg,



Rifampicin 600 mg



N/A12
MultibacillaryDapsone 100 mg,



Rifampicin 600 mg,



Clofazimine 50 mg



N/A24
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