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Leprosy (Hansen’s disease)
is a slowly
progressive, chronic infectious disease caused by the bacillus
Mycobacterium leprae.
It is a very
serious, multilating and stigmatizing disease in many parts of the
world and early diagnosis and therapy is the most important strategy
for its control.
It is highly
infective, but has low pathogenicity and low virulence with a long
incubation period.
The geographical
distribution of leprosy has varied greatly with time and it is now
endemic only in tropical and subtropical regions such as India and
Brazil.
It affects the cooler part of the body, especially the
nasal mucosa, upper respiratory tract, peripheral nerves, testes, the
skin of the ears, and the anterior segment of the eyes.
It is of historical interest that
leprosy was the first
reported bacterial pathogen of mankind. For centuries, leprosy was
widespread in Europe and England. Indeed in 1873 Hansen first saw the lepra bacillus in fresh mounts of scrapings from a leproma
of a Norwegian patient.
A few patients still acquire leprosy in
temperate regions, such as United States and Europe, but most patients
in temperate climates are immigrants who were infected elsewhere.
Lepra bacilli are slender, weakly acid-fast rods.
All attempts to culture the organism have failed or are
unsubstantiated.
Lepra bacilli multiply in experimental animals at
sites with temperature below that of the internal organs, such as the
foot pads of mice, and the ear lobes of hamsters, rats, and other
rodents.
Naturally acquired leprosy has now been
recognized in armadillos (Louisiana and Texas), in a chimpanzee
trapped in Sierra Leone and in a man-gabey monkey captured in
Nigeria.
Lepra bacilli have been experimentally transmitted to
armadillos, whose susceptibility is related, in part, to their low
central body temperature (32 - 35C).
Leprosy exhibits a variety of clinical and
pathologic features.
The lesions vary from the small, insignificant,
and self-healing macules of tuberculoid leprosy to the diffuse,
disfiguring, and sometimes fatal lesions of lepromatous leprosy.
This extreme variation in the
presentation of the disease is not fully understood, but is probably
related to differences in immune reactivity.
Ninety-five percent of all people have
a natural protective immunity and are not infected even through inmate
and prolonged exposure.
In the susceptible 5% who may develop symptomatic
infections, a broad immunologic spectrum ranges from anergy to
hyperergy.
Anergic patients (i.e. those with
little or no resistance) have lepromatous leprosy, whereas hyperergic
patients (those with high resistance) develop tuberculoid leprosy.
“Borderline” leprosy is the term
applied to the broad middle ground into which most patients fall.
Patients with lepromatous leprosy have nodular and
diffuse infiltrates of the skin, eyes, testes, nerves, and organs of
the reticuloendothelial system.
The most severe involvement of the
skin is in exposed areas - the nodular distortions of the face are
called “leonine facies”.
The infiltrates are composed of tumour-like
accumulations of histiocytes , each histiocytes containing enormous
numbers of lepra bacilli.
The epidermis is stretched thinly over the
nodules, and beneath it is narrow, uninvolved “clear zone” of dermis.
Rather than destroying the bacilli, the phagocytic cells appear to act
as microincubators.
Unchecked, these infiltrates expand slowly to distort
and disfigure the face, ears, and upper airway and to destroy the
eyes, eyebrows and eyelashes, nerves, and testes.
Oral
manifestations usually appear in lepromatous leprosy and occur in
20-60% of cases.
They may take the form of multiple nodules (lepromas)
that progress to necrosis and ulceration.
The ulcers are slow to heal,
and produce atrophic scarring or even tissue destruction.
The lesions
are usually located on the hard and soft palate, in the uvula, on the
underside of the tongue, and on the lips and gums.
There may also be
destruction of the anterior maxilla and loss of teeth.
The diagnosis,
based on clinical suspicion, is confirmed through bacteriological and histopathological analyses, as well as by means of the lepromin test (intradermal
reaction that is usually negative in lepromatous leprosy form and
positive in the tuberculoid form).
There is a predominance of suppressor CD8+ over CD4+ T lymphocytes.
Lepromatous tissues are rich in the mRNAs of the TH2 cytokines.
The loss of ability to kill bacteria appears to be
specific for M. leprae. Patients with lepromatous leprosy are not
unusually susceptible to opportunistic infections, cancer, or AIDS and
maintain delayed-type hypersensitivity to Candida, Trichophyton,
mumps, tetanus toxoid, and tuberculin.
Those who are
untreated may die of asphyxiation from an obstructed airway or from
secondary amyloidosis.
The other end of the spectrum is represented by
patients with tuberculoid leprosy, a condition characterized by a
single lesion or very few lesions of the skin.
The hypopigmented macule,
with a raised “infiltrated” border, may be hypesthetic or
anesthetic.
The lesion expands slowly over a period of months or
years, and then gradually heals, although the hypesthesia or
anesthesia remain.
Microscopically, the tuberculoid lesion is a
dermatitis characterized by discrete noncaseating granulomas in the
dermis.
The granulomas are composed of epithelioid cells and Langhan’s
giant cells and are associated with varying numbers of lymphocytes
and plasma cells.
Cutaneous Granulomatous Reaction Pattern
The diagnosis of
tuberculoid leprosy is often difficult on hematoxylin and eosin (H&E)
due to the absence of demonstrable nerve destruction.S-100 is
superior to H&E in identifying nerve fragmentation. It also aids the
differential diagnosis of tuberculoid leprosy.
Cutaneous nerves, including the small dermal nerve
twigs, are eventually destroyed by the bacilli, which accounts for the
sensory deficit.
Patients with borderline leprosy have an endless
variety of features of both lepromatous and tuberculoid leprosy.
The term “indeterminate” leprosy is
used when the biopsy sample is taken from a lesion that is so early in
the course of the disease that the cellular response does not reveal
the type of leprosy.
Thus,
“indeterminate” lesions may heal spontaneously or progress to either lepromators or tuberculoid forms.
The most commonly used drugs, dapsone, rids the
lepromatous patient of lepra bacilli in 4 to 6 years, but it must be
continued indefinitely. Dapsone - resistant strains of M. leprae have
developed, and multidrug regimens are now often used.
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