eMedicine Specialties > Infectious Diseases > Skin and Soft-Tissue Infections

Leprosy: Differential Diagnoses & Workup

Author: D Scott Smith, MD, MSc, DTM&H, Adjunct Assistant Professor, Department of Microbiology and Immunology, Stanford University; Chief of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, Kaiser Redwood City Hospital
Coauthor(s): Tara Ramachandra, Stanford University School of Medicine
Contributor Information and Disclosures

Updated: Aug 19, 2008

Differential Diagnoses

Other Problems to Be Considered

Sensory loss (hypoesthesia) or neuropathy

Amyloidosis
Diabetic neuropathy
Neuropathies due to medications (ie, stavudine, didanosine, acetazolamide, vincristine, gabapentin [Neurontin], isoniazid)
Refsum disease
Sarcoidosis
Vitamin B-12 or folate deficiency

Skin lesions - Flat and hypopigmented

Contact dermatitis
Localized scleroderma
Nevus depigmentosus (congenital lesion)
Onchocerciasis
Pityriasis alba
Pityriasis versicolor
Post–kala-azar dermal leishmaniasis
Seborrheic dermatitis
Tinea corporis (and all dermatophytes)
Vitiligo
Yaws

Skin lesions - Raised and pigmented

Atypical necrobiosis of the face
Cutaneous leishmaniasis
Cutaneous tuberculosis
Follicular mucinosis
Generalized thickening of skin
Granuloma annulare
Granuloma multiforme
Kaposi sarcoma
Lupus erythematosus
Lupus vulgaris
Mycobacterium marinum infection
Myxoedema
Neurofibromatosis
Pachydermoperiostitis
Pityriasis rosea
Psoriasis
Scleroderma
Syphilis
Wegener granulomatosis

Workup

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.7
  • Serologic assays can be used to detect phenolic glycolipid-1 (specific for M leprae) and lipoarabinomannan (commonly seen in mycobacteria).7
  • 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

Other Tests

  • Immunologic tests include the following:
    • 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.
    • 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.
    • 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.
    • 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.
    • Contact or family screening for history of leprosy

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.6

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 (see Image 8). 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 Leprosy topic in eMedicine's Neurology volume.

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.

More on Leprosy

Overview: Leprosy
Differential Diagnoses & Workup: Leprosy
Treatment & Medication: Leprosy
Follow-up: Leprosy
Multimedia: Leprosy
References

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, et al. The continuing challenges of leprosy. Clin Microbiol Rev. Apr 2006;19(2):338-81. [Medline].

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

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

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

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

  7. 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].

  8. [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].

  9. 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].

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

  11. 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].

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

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

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

  15. 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].

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

  17. 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].

Further Reading

Keywords

leprosy, Hansen's disease, Hansen disease, Mycobacterium leprae, M leprae, tuberculoid leprosy, TT leprosy, lepromatous leprosy, LL leprosy, BT leprosy, midborderline leprosy, BB leprosy, borderline lepromatous leprosy, BL leprosy, paucibacillary leprosy, PB leprosy, multibacillary leprosy, MB leprosy, indeterminate leprosy, borderline leprosy

Contributor Information and Disclosures

Author

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

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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: Nothing to disclose.

CME Editor

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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.