• Leprosy (Hansen's disease) can be defined as a chronic
granulomatous infection and its sequelae, caused by
Mycobacterium leprae, and affecting primarily skin and
• 600,000 new cases yearly, worldwide
• despite apparently curative antibacterial therapy, one-
quarter to one-third of all patients will have a
debilitating and permanent neurologic deficit.
Father Damien with leprosy patients he
ministered to in Hawaii during the 1870s;
he was later canonized by the Roman
• Primarily a disease of developing countries, is
endemic in all continents, except Antarctica.
• The highest case detection rates are in India, Brazil,
Madagascar, Nepal, and Tanzania.
• More common in men than in women by a 2:1 ratio
• Predominantly a young person's disease, the
majority of cases occurring before age 35 years
ETIOLOGY AND PATHOGENESIS
• M. leprae, the cause of leprosy, is a noncultivable,
gram-positive, obligate intracellular, acid-fast bacillus.
• Entry into nerves is mediated by the binding of the
species-specific trisaccharide in phenolic glycolipid I to
laminin-2 in the basal lamina of Schwann cell-axon
units, 11providing a rationale as to why M. leprae is
the only bacterium known to invade peripheral nerves.
• The most detailed description of the granulomatous
spectrum of leprosy came from Ridley and his
associates, integrating both clinical and histologic
TT (polar tuberculoid), BT (borderline tuberculoid), BB
(borderline), BL (borderline lepromatous), LLs (subpolar
lepromatous), and, finally, LLp (polar lepromatous)
Peripheral Nerve Changes
• Four types of peripheral nerve abnormalities are common in
(1) nerve enlargement (usually perceived as asymmetry),
particularly in those close to the skin, such as the great
auricular, ulnar, radial cutaneous, superficial peroneal, sural and
(2) sensory loss in skin lesions;
3) nerve trunk palsies either with signs and symptoms of
inflammation or without such overt manifestations, that is,
silent neuropathy, usually with both sensory and motor loss
(weakness and/or atrophy) and, if long-standing, also with
(4) acral distal symmetric anesthesia, a withering away, so to
speak, of the type C fibers, involving heat and cold
discrimination before loss of pain or light touch, beginning in
acral areas and, over time, extending centrally but sparing the
palms, at least for a while.
The most commonly affected
nerves in leprosy.
(From Sabin TD, Swift TR,
Jacobson RR: Leprosy. In: Dyck
PJ, Thomas PK, eds: Peripheral
Elsevier Saunders. 2005, p
2089, Figure 91-4.)
POLAR TUBERCULOID LEPROSY
A solitary, anesthetic, and
annular lesion of polar
tuberculoid leprosy (TT),
which had been present for
3 months. Its sharp margins,
erythema, and scale are
more evident than its
elevation. The central red
dots are the sequelae or
“footprints” of testing for
pinprick perception when it
is absent. (If present, the
One of several lesions of
(BT), which had an
with satellite papules.
Compared to the TT lesion,
there is less erythema, no
evident scales, but sharp
margination, and the
footprints of absent
pinprick perception are
BORDERLINE TUBERCULOID LEPROSY
• BB is the immunologic midpoint or mid-zone of the granulomatous
spectrum, being its most unstable area, with patients quickly up- or
downgrading to a more stable granulomatous posture with or
without a clinical reaction.
• Characteristic skin changes are annular lesions with sharply
marginated interior and exterior margins, large plaques with
islands of clinically normal skin within the plaque, giving a
“Swiss cheese” appearance, or the classic dimorphic lesion.
• Because of instability, the BB posture is short-lived and such
patients are evidently rarely seen.
BORDERLINE LEPROMATOUS LEPROSY
A characteristic borderline or
dimorphic lesion, which is an
indurated and elevated
annular plaque that
has a well defined
margin, but a poorly defined
margin. Having both
morphologies, it is termed
Multiple lesions in a patient
lepromatous (BL) leprosy.
The annular lesions vary in
and are asymmetrically
distributed. In contrast, the
poorly defined papular and
nodular lesions are roughly
Loss of sensation was
present in most lesions.
Multiple skin-colored papular
and small nodular lesion in a
patient with polar lepromatous
leprosy. The margination of the
lesions is variable, some being
poorly defined. The absence of
clinical inflammation is
evident. Some distortion of the
normal helix is arising from
diffuse infiltration as well as
from the nodular lesions.
Multiple papular lesions,
which are solitary and
confluent, in a patient with
subpolar lepromatous (LLs)
These multiple, barely palpable, erythematous,
and asymptomatic lesions had been erupting
over the previous 2 months in a LLs patient.
With treatment, as lesions remitted they
became mildly hyperpigmented.
With progressive bacillary proliferation, further cellular
infiltration, and the consequent thickening of the dermis,
the skin is thrown into folds producing the leonine faces
often in conjunction with nodular lesions.
• Because of motor or sensory
changes in cranial nerve V, the
eye may be at risk in TT and BT
disease, as well as in BB, BL, and
• numerous changes in the cornea
and anterior chamber are
possible, iritis being a common
• Corneal insensitivity is the
common, treatable change.
• Indeterminate leprosy is a term with nearly as many meanings
as it has users:
- “designating an early lesion, appearing before the host
makes a definitive immunologic commitment to cure or to an
overt granulomatous response.”
• hypopigmented macule
• with or without a sensory deficit
• acid-fast bacilli, if found, are in very small numbers
• rare in clinic
Indeterminate leprosy, A solitary erythematous macule on
the face of a young family member of a patient with
Variants: PREGNANCY AND POSTPARTUM
• Pregnancy is a precipitating factor for leprosy in 10 to 25
percent of women patients.
• Of the drugs used to treat leprosy, none have been proven to
be safe for the fetus and one is clearly contraindicated.
• Fetal damage attributable to dapsone evidently has not been
observed, hence continuation of dapsone in multibacillary
patients is usually recommended.
• The wishes of the patient should be carefully considered.
Untreated, lactating BL and LL patients have viable bacilli in
their milk, but no definable risk has been identified in infants
ingesting such bacilli.
• Most laboratory changes occur in LL or extensive BL disease.
• Hyperglobulinemia -> increased sedimentation rate
• A biologic false-positive serologic test for syphilis, anemia of
chronic disease, and mild lymphopenia are also common
• Clinically insignificant antiphospholipid antibodies are present
in 50 percent of LL patients, and may give rise to a lupus
anticoagulant or agglutination of sheep erythrocytes (Rubino
• Elevated serum lysozyme and angiotensin-converting enzyme
• Proteinuria, not uncommon, is associated with a focal
• High serumfollicle-stimulating hormone (FSH) and luteinizing
hormone (LH) values, but low testosterone levels
• A firm diagnosis of leprosy requires the satisfaction of one of
- a consistent peripheral nerve abnormality
- the demonstration of mycobacteria in tissues.
• Risk factors:
-(1) birth or residence in an endemic area, which is almost
sine qua non for the diagnosis
-(2) a blood relative with the disease, which could reflect
transmission, common genetic makeup, or common
- (3) armadillo (seven-banded) exposure in North American.
• The possibility of leprosy also should be suggested by
particular clinical constellations such
- (1) simultaneous skin lesions and peripheral nerve
- (2) a differential diagnosis that includes granuloma, vasculitis,
- (3) a peripheral neuropathy of unknown type in a patient in or
from an endemic area, the so called pure neuritic leprosy
- (4) simultaneous palsies of cranial nerves V and VII,
considered to be leprosy until proven otherwise.
• Medical management is directed at the infection itself, or if
present, at a reactional state.
- For paucibacillary disease (TTor BT) the World Health
Organization (WHO) recommends the combination of
unsupervised dapsone (bacteriostatic) 100 mg daily and
supervised rifampin (bactericidal) 600 mg monthly for a
duration of 6 months.
- For multibacillary disease (BB, BL, and LL) the WHO
recommends unsupervised dapsone 100 mg daily, supervised
rifampin 600 mg monthly and clofazimine 50 mg daily,
unsupervised, and 300 mg monthly supervised for a routine
duration of 2 years.