Home > D. Systemic pathology > Infectious diseases > leprosy


Tuesday 17 March 2009

Digital slides

- UI: - Tuberculoid leprosy.
- JRC:568 : Cutaneous leprosy.

Definition: Leprosy, or Hansen disease, is a slowly progressive infection caused by Mycobacterium leprae, affecting the skin and peripheral nerves and resulting in disabling deformities.

Mycobacterium leprae is, for the most part, contained within the skin, but leprosy is likely to be transmitted from person to person through aerosols from lesions in the upper respiratory tract. Inhaled M. leprae, like M. tuberculosis, is taken up by alveolar macrophages and disseminates through the blood, but grows only in relatively cool tissues of the skin and extremities. Despite its low communicability, leprosy remains endemic among an estimated 10 to 15 million people living in poor tropical countries.

The Ridley-Jopling classification

The Ridley-Jopling classification is used to differentiate types of leprosy and helps in determining the prognosis. Purely neuritic leprosy (asymmetrical peripheral neuropathies with no evident skin lesions), with or without tenosynovitis and symmetric polyarthritis, is also possible. A general classification of disease is based on the number of skin lesions present and the number of bacilli found on tissue smears. Paucibacillary disease (indeterminate leprosy and tuberculoid leprosy) has fewer than 5 lesions and no bacilli on smear testing. Five or more lesions with or without bacilli (borderline leprosies and lepromatous leprosy) is considered multibacillary disease.

- indeterminate leprosy
- tuberculoid leprosy
- borderline tuberculoid leprosy
- borderline borderline leprosy
- borderline lepromatous leprosy
- lepromatous leprosy
- histoid leprosy


Mycobacterium leprae is an acid-fast obligate intracellular organism that grows very poorly in culture but can be grown in the armadillo. Mycobacterium leprae grows more slowly than other mycobacteria and grows best at 32° to 34°C, the temperature of the human skin and the core temperature of armadillos.

Like M. tuberculosis, Mycobacterium leprae secretes no toxins, and its virulence is based on properties of its cell wall. The cell wall is similar enough to that of M. tuberculosis that immunization with bacille Calmette-Guérin (BCG) confers some protection against Mycobacterium leprae infection. Cell-mediated immunity is reflected by delayed type hypersensitivity reactions to dermal injections of a bacterial extract called lepromin.

Leprosy has two strikingly different patterns of disease.

Patients with the less severe form, tuberculoid leprosy, have dry, scaly skin lesions that lack sensation. They often have large, asymmetric peripheral nerve involvement.

The more severe form of leprosy, lepromatous leprosy, includes symmetric skin thickening and nodules. This is also called anergic leprosy, because of the unresponsiveness (anergy) of the host immune system. Cooler areas of skin, including the earlobes and feet, are more severely affected than warmer areas, such as the axilla and groin.

In lepromatous leprosy, damage to the nervous system comes from widespread invasion of the mycobacteria into Schwann cells and into endoneural and perineural macrophages.

In advanced cases of lepromatous leprosy, Mycobacterium leprae is present in sputum and blood.

People can also have intermediate forms of disease, called borderline leprosy.

The T-helper lymphocyte response to M. leprae determines whether an individual has tuberculoid or lepromatous leprosy. Patients with tuberculoid leprosy have a TH1 response, with production of IL-2 and IFN-γ. As with M. tuberculosis, IFN-γ is critical to mobilizing an effective host macrophage response. IL-12, which is produced by antigen presenting cells, is important to the generation of TH1 cells.

Low levels of IL-12 or unresponsiveness of T cells to this cytokine may reduce the TH1 response, leading to lepromatous leprosy. In addition to TH1 cells, lymphocytes bearing the γ/δ T-cell receptor infiltrate the lesions of leprosy and produce IFN-γ in patients with tuberculoid leprosy.

Patients with lepromatous leprosy have a defective TH1 response or a dominant TH2 response, with production of IL-4, IL-5, and IL-10, which may suppress macrophage activation in response to M. leprae.

In some cases, antibodies are produced against M. leprae antigens. Paradoxically, these antibodies are usually not protective, but they may form immune complexes with free antigens that can lead to erythema nodosum, vasculitis and glomerulonephritis.

Forms and types

- early and indeterminate leprosy
- tuberculoid leprosy
- borderline tuberculoid leprosy
- borderline leprosy
- borderline lepromatous leprosy
- lepromatous leprosy
- histoid leprosy
- diffuse leprosy of Lucio and Latapí

The two main forms are tuberculoid leprosy and lepromatous leprosy.


The following genes have been associated with leprosy; hence, susceptibility to leprosy may be at least partially inheritable :

- Susceptible loci have been found on band 10p13 and chromosome 6.
Associations include HLA-DR2 and HLA-DR3 (tuberculoid disease), as well as HLA-DQ1 (lepromatous leprosy).

- HLA-DRB1*04 is associated with resistance, and HLA-DRB1*10 is associated with susceptibility to leprosy in Brazilian and Vietnamese patients.

Genetic variants have been found in the shared promoter region of the PARK2 (parkin) and PACRG genes expressed on monocytes.

- Lymphotoxin-alpha (LTA) + 80 expressed on dendritic cells appears to be a risk factor for early-onset leprosy, independent of PARK2/PARCG and HLA class I and HLA-DRB1 genes.

- Polymorphisms in the gene promoter regions of TNF (multibacillary leprosy) and IL-10 (-819T allele) are noted in leprosy susceptibility.

- Mutations in TLR1 and TLR2 may be involved in susceptibility and/or resistance to other infectious diseases.

- Polymorphisms in the NRAMP1 gene appear on macrophages in multibacillary disease in African patients.

- TaqI polymorphism (tt genotype) at exon 9 of the vitamin D receptor gene is noted.


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