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Review Article
Leprosy: An Overview of Pathophysiology
Ramesh Marne Bhat and Chaitra Prakash
Department of Dermatology, Father Muller Medical College, Karnataka, Mangalore 572002, India
Correspondence should be addressed to Ramesh Marne Bhat, rameshderma@gmail.com
Received 25 May 2012; Accepted 25 July 2012
Academic Editor: Eliete Calo Romero
Copyright 2012 R. M. Bhat and C. Prakash. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Leprosy, also known as Hansens disease, is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that
has a predilection for the skin and nerves. The disease is clinically characterized by one or more of the three cardinal signs:
hypopigmented or erythematous skin patches with definite loss of sensation, thickened peripheral nerves, and acid-fast bacilli
detected on skin smears or biopsy material. M. leprae primarily infects Schwann cells in the peripheral nerves leading to nerve
damage and the development of disabilities. Despite reduced prevalence of M. leprae infection in the endemic countries following
implementation of multidrug therapy (MDT) program by WHO to treat leprosy, new case detection rates are still high-indicating
active transmission. The susceptibility to the mycobacteria and the clinical course of the disease are attributed to the host immune
response, which heralds the review of immunopathology of this complex disease.
1. Introduction
2. Mycobacterium leprae
Leprosy, also known as Hansens disease, is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that has a predilection for the skin and nerves. Though
nonfatal, leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The disease has
been known to man since time immemorial. DNA taken
from the shrouded remains of a man discovered in a tomb
next to the old city of Jerusalem shows him to be the
earliest human proven to have suered from leprosy. The
remains were dated by radiocarbon methods to 150 A.D.
[1]. The disease probably originated in Egypt and other
Middle Eastern countries as early as 2400 BCE. An apparent
lack of knowledge about its treatment facilitated its spread
throughout the world. Mycobacterium leprae, the causative
agent of leprosy, was discovered by G. H. Armauer Hansen in
Norway in 1873, making it the first bacterium to be identified
as causing disease in humans [2, 3]. Over the past 20 years,
the WHO implementation of MDT has rendered leprosy a
less prevalent infection in 90% of its endemic countries with
less than one case per 10,000 population. Though, it continues to be a public health problem in countries like Brazil,
Congo, Madagascar, Mozambique, Nepal, and Tanzania [4].
polymorphism (SNP) association studies showed a low lymphotoxin- (LTA)-producing allele as a major genetic risk
factor for early onset leprosy [13]. Other SNPs to be associated with disease and/or the development of reactions in
several genes, such as vitamin D receptor (VDR), TNF-, IL10, IFN-, HLA genes, and TLR1 are also suggested [1417].
Linkage studies have identified polymorphic risk factors in
the promoter region shared by two genes: PARK2, coding
for an E3-ubiquitin ligase designated Parkin, and PACRG
[18]. A study also suggests that NOD2 genetic variants are
associated with susceptibility to leprosy and the development
of reactions (type I and type II) [19].
4. Transmission
5. Incubation Period
8. Disease Classification
Leprosy is classified within two poles of the disease with transition between the clinical forms [42]. Clinical, histopathological, and immunological criteria identify five forms of
leprosy: tuberculoid polar leprosy (TT), borderline tuberculoid (BT), midborderline (BB), borderline lepromatous (BL),
and lepromatous polar leprosy (LL). Patients were divided
into two groups for therapeutic purposes: paucibacillary (TT,
BT) and multibacillary (midborderline (BB), BL, LL) [43]. It
was recommended later that the classification is to be based
on the number of skin lesions, less than or equal to five
for paucibacillary (PB) and greater than five for the multibacillary (MB) form.
6. Risk Factors
Those living in endemic areas with poor conditions such
as inadequate bedding, contaminated water, and insucient
diet, or other diseases that compromise immune function are
at highest risk for acquiring M. leprae infection. There has
Tuberculoid
Single or upto 3
Borderline tuberculoid
Midborderline
Several (1030)
Variable
Hypopigmented
Absent
Markedly diminished
Moderately diminished
Hair growth
Nil
Markedly diminished
Skin smear
Negative
Negative or 1+
13+
Strongly positive
Weakly positive
Negative
Surface changes
Sensations
Lepromin test
Borderline
lepromatous
Numerous,
asymmetrical
(>30)
Small, some
can be large
Shiny
Slightly
diminished
Slightly
Moderately diminished
diminished
35+
Negative
Lepromatous leprosy
Innumerable,
symmetrical
Small
Shiny
Minimally diminished
Not aected initially
Plenty, including globi
(6+)
Negative
4
by upgrading of the clinical picture towards the tuberculoid pole, including a reduction in bacillary load. Immunologically, it is characterized by the development of strong skin
test reactivity as well as lymphocyte responsiveness and a
predominant Th1 response [54, 55]. RR episodes have been
associated with the infiltration of IFN- and TNF-secreting
CD4+ lymphocytes in skin lesions and nerves, resulting in
edema and painful inflammation [56, 57]. Immunologic
markers like CXCL10 are described as a potential tool for
discriminating RR [58]. A significant increase in FoxP3
staining was observed in RR patients compared with ENL
and patients with nonreactional leprosy, implying a role for
regulatory T cells in RR [59].
Pathogenesis of type II reaction is thought to be related to
the deposition of immune complexes [60]. Increased levels of
TNF-, IL-1, IFN-, and other cytokines in type II reactions
are observed [6163]. In addition, C-reactive protein, amyloid A protein, and -1 antitrypsin have also been reported
to be elevated in ENL patients sera [64]. A massive infiltrate
of polymorphonuclear cells (PMN) in the lesions is only
observed during ENL and some patients present with high
numbers of neutrophils in the blood as well. Neutrophils may
contribute to the bulk of TNF production that is associated
with tissue damage in leprosy. More recently, microarray analysis demonstrated that the mechanism of neutrophil recruitment in ENL involves the enhanced expression of E-selectin
and IL-1, likely leading to neutrophil adhesion to endothelial cells; again, an eect of thalidomide on PMN function
was observed since this drug inhibited the neutrophil recruitment pathway [65]. Altogether, the data highlight some of
the possible mechanisms for thalidomides ecacy in treating type II reaction. TNF- may augment the immune response towards the elimination of the pathogen and/or mediate the pathologic manifestations of the disease. TNF-
can be induced following stimulation of cells with total,
or components of M. leprae, namely, lipoarabinomannan
(the mycobacteria lipopolysaccharide- like component) a
potent TNF inducer [66]. In addition, mycolyl-arabinogalactan-peptidoglycan complex of Mycobacterium species, the
protein-peptidoglycan complex, and muramyl dipeptide all
elicit significant TNF- release [66].
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