Hansen's Disease (Leprosy)

Current and Future Pharmacotherapy and Treatment of Disease-related Immunologic Reactions

Davey P. Legendre, Pharm.D.; Christina A. Muzny, M.D.; Edwin Swiatlo, M.D., Ph.D.

Disclosures

Pharmacotherapy. 2012;32(1):27-37. 

In This Article

Pathogenesis

The mode of transmission of M. leprae has not been absolutely proven; however, the most common mechanism is thought to occur through the respiratory route in a manner similar to that of tuberculosis. Inoculation of bacilli through broken skin and other close physical contact has also been implicated. In the southeastern United States, armadillos carry M. leprae, and contact with these animals is presumed to cause some infections in this region. Most people are resistant to infection with M. leprae; however, certain genotypes are increasingly recognized as risk factors for leprosy. Both human leukocyte antigen (HLA) and non-HLA alleles have been linked to susceptibility to infection.[15] A recent genomewide association study in eastern China associated variant genes in the NOD2 signaling pathway with susceptibility to infection with M. leprae.[16]

The pathogenesis of infection with M. leprae is poorly understood, but most evidence suggests that clinical manifestations of infection result primarily from host immune responses to the leprosy bacillus. Classified on the basis of the Ridley-Jopling scale or by the World Health Organization (WHO), the immune response to M. leprae varies over a large continuum and is thought to be responsible for the heterogeneous clinical appearance of leprosy.[17,18,19] The Ridley-Jopling scale combines clinical, immunologic, and histopathologic evidence and recognizes five forms of leprosy: tuberculoid, borderline tuberculoid, midborderline, borderline lepromatous, and lepromatous leprosy. The WHO classification scheme is superimposed on the Ridley-Jopling scale to fit two distinct multidrug therapy regimens and consists of two broad categories: paucibacillary disease, which includes the tuberculoid and borderline tuberculoid forms, and multibacillary disease, which includes the midborderline, borderline lepromatous, and lepromatous forms (Figure 1).

Figure 1.

Relationships of bacterial burden, immune response, and clinical classification schemes. The five forms of leprosy based on the Ridley-Jopling Scale are tuberculoid (TT), borderline tuberculoid (BT), midborderline (BB), borderline lepromatous (BL), and lepromatous (LL). CMI = cell-mediated immunity; AFB = acid-fast bacilli.

At the paucibacillary tuberculoid end of the spectrum, skin and nerve lesions have characteristics of well-developed T helper cell type 1 (Th1)–mediated immune responses and possess few acid-fast bacilli that signify presence of the organism. This form of leprosy typically is associated with a low burden of organisms and few skin lesions. In contrast, at the multibacillary lepromatous end of the spectrum, Th2-type cellular immune responses predominate, with numerous skin lesions containing many acid-fast bacilli. This form of infection results in multiple progressive skin lesions and may extensively involve peripheral nerves. Between these two phenotypic extremes is a highly variable continuum of clinical disease that is marked by dynamic immunologic responses to M. leprae.

The clinical manifestations of infection in an individual may evolve in a waxing and waning manner dependent on the predominant immunologic response at any time. These clinical forms of infection have been studied in the context of gene expression profiling,[20] and this approach has uncovered new insights into the mechanisms underlying the regulation of disparate immune responses to M. leprae.

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