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LEPROSY: AN OVERVIEW OF
PATHOPHYSIOLOGY
RESTU WULANDARI
I11110062
PEMBIMBING
DR. TEGUH ALYANSYAH SP.KK
Journal
Ramesh Marne Bhat and Chaitra
Prakash
Introduction
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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 probably originated in Egypt and
other Middle Eastern countries as early as 2400
BCE
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
Mycobacterium leprae
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M. leprae, an acid-fast bacillus is a major
human pathogen.
In addition to humans, leprosy has been
observed in ninebanded armadillo and
three species of primates
The bacterium can also be grown in the
laboratory by injection into the footpads
of mice
Genetic Determinants of Host
Response
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Human genetic factors influence the acquisition
of leprosy and the clinical course of disease
Single-nucleotide polymorphism (SNP)
association studies showed a low lymphotoxin(LTA)-producing allele as a major genetic risk
factor for early onset leprosy
Other SNPs to be associated with disease
and/or the development of reactions in several
genes, such as vitamin D receptor (VDR), TNF-,
IL-10, IFN-, HLA genes, and TLR1
Genetic Determinants of Host
Response
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polymorphic risk factors in the promoter
region shared by two genes: PARK2,
coding for an E3-ubiquitin ligase
designated Parkin, and PACRG
A study also suggests that NOD2 genetic
variants are associated with
susceptibility to leprosy and the
development of reactions (type I and
type II)
Transmisions
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Two exit routes of M. leprae from the
human body often described are the skin
and the nasal mucosa
Lepromatous cases show large numbers
of organisms deep in the dermis,
Although there are reports of acid-fast
bacilli being found in the
desquamating epithelium of the
skin
Transmisions
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There are reports that no acid-fast bacilli
were found in the epidermis, However,
fairly large numbers of M. leprae were
found in the superficial keratin layer of
the skin of lepromatous leprosy patients,
suggesting that the organism could exit
along with the sebaceous secretions
Transmisions
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The quantity of bacilli from nasal
mucosal lesions in lepromatous leprosy
ranges from 10,000 to 10,000,000
Majority of lepromatous patients show
leprosy bacilli in their nasal secretions as
collected through blowing the nose
Nasal secretions from lepromatous
patients could yield as much as 10
million viable organisms per day
Incubation Period
The minimum incubation period reported is as
short as a few weeks and this is based on the
very occasional occurrence of leprosy among
young infants
The maximum incubation period reported is as
long as 30 years, or over, as observed among
war veterans known to have been exposed for
short periods in endemic areas but otherwise
living in nonendemic areas.
The average incubation period is between three
and ten years
Risk Factors
Those living in endemic areas with poor
conditions such as inadequate bedding,
contaminated water, and insufficient
diet, or other diseases that compromise
immune function are at highest risk for
acquiring M. leprae infection.
Interaction of M. leprae with
Schwann Cells and Macrophages
Schwann cells (SCs) are a major target for
infection by M. leprae leading to injury of the
nerve, demyelination, and consequent disability.
Binding of M. leprae to SCs induces
demyelination and loss of axonal conductance .
It has been shown that M. leprae can invade SCs
by a specific laminin binding protein of 21 kDa
in addition to PGL-1 PGL-1, a major unique
glycoconjugate on the M. leprae surface, binds
laminin-2, which explains the predilection of the
bacterium for peripheral nerves
Interaction of M. leprae with
Schwann Cells and Macrophages
The identification of the M. lepraetargeted SC receptor, dystroglycan (DG),
suggests a role for this molecule in early
nerve degeneration.
Mycobacterium leprae-induced
demyelination is a result of direct
bacterial ligation to neuregulin receptor,
ErbB2 and Erk1/2 activation, and
subsequent MAP kinase signaling and
proliferation
Interaction of M. leprae with
Schwann Cells and Macrophages
Macrophages are one of the most abundant
host cells to come in contact with
mycobacteria. Phagocytosis of M. leprae by
monocyte-derived macrophages can be
mediated by complement receptors CR1
(CD35), CR3 (CD11b/CD18), and CR4
(CD11c/CD18) and is regulated by protein
kinase
Nonresponsiveness towards M. leprae seems
to correlate with a Th2 cytokine profile.
Disease Classification
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)
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.
Clinical Features
Clinical Features
a.
Indeterminate Leprosy
Indeterminate (I) is characterized by an
ill-defined, bizarre hypopigmented
macule(s) with a smooth or scaly
surface. The sensations over the macule
may or may not be impaired. The nerve
proximal to the patch may or may not be
thickened.
Clinical Features
b. Polyneuritic Leprosy.
Manifesting with only neural signs
without any evidence of skin lesions. The
affected nerves are thickened, tender, or
both.
Clinical Features
c. Histoid Leprosy.
Histoid leprosy is relatively uncommon, distinct
clinical, and bacteriologic and histopathologic
expression of multibacillary leprosy .It may
occur as a primary manifestation of the disease
or in consequence to secondary drug resistance
to dapsone following irregular and inadequate
monotherapy.
manifests as numerous cutaneous nodules and
plaques primarily over the back, buttocks, face,
and bony prominences.
Histopathological
Reactions
Histopathologically, skin lesions from
tuberculoid patients are characterized by
inflammatory infiltrate containing
wellformed granulomas with
differentiated macrophages, epithelioid
and giant cells, and a predominance of
CD4+ T cells at the lesion site, with low
or absent bacteria.
Histopathological
Reactions
Lepromatous patients present with
several skin lesions with a
preponderance of CD8+ T cells in situ,
absence of granuloma formation, high
bacterial load, and a flattened epidermis
Leprosy Reactions
Leprosy reactions are the acute episodes
of clinical inflammation occurring during
the chronic course of disease.
They are classified as type I (reversal
reaction; RR) or type II (erythema
nodosum leprosum; ENL) reactions.
Type I reaction occurs in borderline
patients (BT, midborderline and BL)
whereas ENL only occurs in BL and LL
forms
Leprosy Reactions
Type I reaction is characterized by edema
and erythema of existing skin lesions, the
formation of new skin lesions, neuritis,
additional sensory and motor loss, and
edema of the hands, feet, and face, but
systemic symptoms are uncommon. The
presence of an inflammatory infiltrate with
a predominance of CD4+ T cells,
differentiated macrophages and thickened
epidermis have been observed in RR
Leprosy Reactions
.Type II reaction is characterized by the
appearance of tender, erythematous,
subcutaneous nodules located on
apparently normal skin, and is frequently
accompanied by systemic symptoms,
such as fever, malaise, enlarged lymph
nodes, anorexia, weight loss, arthralgia,
and edema
Conclusions
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.
Conclusions
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.
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