Leprosy Workup

Updated: Apr 07, 2023
  • Author: Darvin Scott Smith, MD, MSc, DTM&H, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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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 1 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

This definition does not include patients who have completed an entire round of treatment but still have residual disabilities. The WHO recommendation as of 2018 is to continue to base diagnosis on the above clinical presentation combined with a confirmatory laboratory test, such a slit-skin smear or biopsy.

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. [16]
  • Serologic assays can be used to detect phenolic glycolipid-1 (specific for M leprae) and lipoarabinomannan (commonly seen in mycobacteria). [16] However, serological tests show low sensitivity for paucibacillary leprosy.
  • 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.

Although the necessity of point-of-care and rapid diagnostic tests is recognized, these types of tests have yet to be developed.

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:

  • 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. [17]
  • 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


Skin biopsy samples stained with hematoxylin-eosin and Fite-Faraco or Ziehl-Neelsen 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 also may 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. [18]


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-f 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, MD, 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.



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.