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Leprosy
Delphine J. Lee, Thomas H. Rea, & Robert L.
Modlin
HISTORICAL ASPECTS
Leprosy is an ancient disease; sacred writings from
India in the sixth century bc give a good description of a similar or identical illness. By the second
century ad, Greek physicians in Europe wrote descriptions of the disease, evidently well established
by that time. Stigmatization of patients with leprosy
remains an unfortunate but enduring legacy
of the European pandemic that occurred from
1,0001,500 ad Hansens attribution of Mycobacterium leprae as its etiologic agent in 1873 marks the
beginning of scientific leprology.1
Effective chemotherapy began with the introduction of sulfones in 1943. In 1961, the limited growth
of M. leprae in the mouse footpad provided a way
to screen for therapeutic agents and to identify
drug resistance.2 In 1970, rifampin was the first drug
to be identified as bactericidal for M. leprae and is
now the cornerstone of most therapeutic regimens.
Ridley and his associates3 provided a detailed account of the granulomatous spectrum of leprosy
that is useful to clinicians and pathologists and essential to subsequent immunologic studies. Jopling
clearly defined and separated the two common
reactional states.
In 1919, the lepromin skin test inaugurated
systematic study of host resistance as the source
of disease diversity,4 with lymphocyte transformation tests being established in the 1960s as an in
vitro correlate. The recognition of leprosy in the
nine-banded armadillo, in 1971, provided a source
of large quantities of highly purified M. leprae for a
wide variety of investigations,5 culminating in the
sequencing of the entire genome of M. leprae in
2001.6
EPIDEMIOLOGY
Now primarily a disease of developing countries,
leprosy is endemic in all continents, except Antarctica. In the Americas, only Canada and Chile are not
endemic countries, with Texas and Louisiana having
endemic foci in the United States. The southernmost nations of Europe have a very low incidence,
CLINICAL FINDINGS
Reactional States
LUCIOS PHENOMENON HISTOLOGY.
Lucio lesions feature ischemic necrosis in the epidermis and its appendages, vessel occlusion in the
deep dermis by thrombosis or endothelial proliferation, and also a feature of normal-appearing skin in
patients with Latapis lepromatosis heavy bacillary
parasitization of endothelial cells.38 When an early
infarct is sampled (eFigs. 186-8.12 and 186-8.13),
necrotic nuclei in the epidermis and upper dermis failed to stain normally, but early reparative
changes are found at the junction of the infarcted
and noninfarcted tissues. When an older lesion
is sampled, this necrotic epidermis, recognizable
because of ghost cells and residual melanin, can be
recognized above a new stratum corneum, and epidermis (eFig. 186-8.14). When a still older lesion is
sampled, the necrotic epidermis that is so conspicuous clinically may be lost during tissue processing. Passive congestion of superficial vessels with
extravasation of erythrocytes and necrosis of skin
appendages may be well developed in early lesions,
but diminishes with the passage of time. In the
early lesions, proliferation of endothelial cells with
heavy parasitization by bacilli and/or thrombus formation in the deep dermal vessels is conspicuous,
affording a tempting explanation for the infarct.
These changes also diminish with time. There is
little inflammatory change in the infarct, with what
there is entering from the adjacent viable tissue,
supporting the idea that Lucios phenomenon is
best described as a vasculosis, not as a vasculitis.
This having been said, in a minority of specimens,
a lepromatous-granulates vasculitis of unknown
significance has been described at the dermalsubcutaneous interface.39
Immunopathology and
Immunology
Investigation into the immunology of leprosy
offers three promises: (1) a better understanding of
the disease itself; in particular, the immunopathogenesis of the granulomatous spectrum and the
reactional states; (2) eradication or control of the
disease by vaccination; and (3) development of a
probe of cell-mediated immunity (CMI) in humans
that, when understood in the model of leprosy,
will illuminate other disease processes. The immunopathogenesis of the granulomatous spectrum
Chapter 186:
TREATMENT
Medical management is directed at the infection
itself (Box 186-2), and if present, at a reactional
state (Box 186-3).54 A patient is considered to be
paucibacillary if no AFB are found in tissue or
smears, and to be multibacillary if one or more
AFB are found. The rationale for the three drug
Leprosy 285
tive within 2 weeks), we increase the dose of thalidomide until obtaining a therapeutic or toxic effect,
having gone as high as 600 mg at bedtime. Toxic
effects include drowsiness, dizziness, orthostatic
hypotension, constipation, neutropenia, and hypersensitivity reactions, and neuropathy. Some recommend daily baby aspirin when starting thalidomide
because of potential thromboembolic events.
Thalidomide is slowly tapered over months once
a patient has been stable with no skin lesions for
approximately 6 months. The goal of treatment is
the abolition of systemic symptoms and morbidity
from skin lesions, not the elimination of skin lesions.
Patients who still have some active skin lesions but
no systemic symptoms, should be maintained on
their current dose, and patients often worsen if the
dose is reduced. In our experience patients requiring thalidomide for the treatment of ENL require
an approximate median duration of 5 years on this
drug. If thalidomide cannot be used then corticosteroids may well be needed. Clofazimine, acting as
a steroid-sparing agent, is recommended by some
at a dose of 300 mg daily. (To lessen gastrointestinal
intolerance, increasing the daily dose in 100 mg
increments at weekly intervals is recommended.)
Management with nonsteroidal anti-inflammatory
agents or pentoxifylline has been found useful by
some, but has been disappointing in our hands.
Adverse reactions to dapsone seen in the near
term include the dapsone syndrome, a rare, potentially fatal infectious mononucleosis-like condition and three kinds of hemolytic anemia, almost
universally from a direct erythrocyte membrane
effect, uncommonly from a glucose-6-phosphate
deficiency. In the long term, dapsone is associated
with peripheral neuropathy, usually motor with a
sensory component, and, rarely, bone marrow suppression, especially agranulocytosis.
The serious problem with rifampin is hepatotoxicity. Red urine is alarming but not indicative
of pathology. As a P450 inducer, rifampin may
lessen the effect of other drugs, for example, oral
contraceptives resulting in pregnancy, or reduced
anti-inflammatory activity of corticosteroids. Once
monthly use of rifampin is rarely associated with
severe hemolysis and acute renal failure.
Clofazimine produces skin darkening from the
clofazimine itself in the near term and from a
ceroid-lipofuscin pigment in the long term (eFig.
186-8.15).60 At usual doses of 50100 mg a day,
gastrointestinal intolerance, dry skin, and acquired
ichthyosis are common. Prolonged administration
Chapter 186:
PREVENTION
Protocols endeavoring to control leprosy by vaccination usually consist of BCG alone, viable BCG
in combination with killed M. leprae, or killed M.
leprae alone.61 Most studies support a reduction in
leprosy incidence, roughly one-third in tuberculoid
cases, considerably less in lepromatous. The recent
observation that lipid and lipoglycan antigens are
presented to T cells (CD4, CD8, CD3+) by CD1+ cells
opens the door to entirely new vaccination protocols.62 Other preventive measures, such as isolation
of patients or prophylactic treatment of patient
contacts with antimicrobials, have been disappointing.
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