Chronic granulomatous infectious disease.
Caused by Mycobacterium leprae
Mainly involves the peripheral nerves and skin
Other organs may involve:
Mucosa of mouth
Upper respiratory tract
Bones & Muscles.
Commonly involves every organ except :
CNS, Ovary and Lungs.
Worldwide distribution but essentially a disease of developing
The prevalence rate has dropped by 90 percent from
21.1cases/10000 in 1985 to <1/10000 in 2000.
To date there has been no resistance to antileprosy medicines
when used as MDT.
Leprosy Situation in India
The goal of leprosy elimination at National level (i.e. PR of <1 case/10,000
population) as set by National Health Policy 2002 had been achieved in the month
of December 2005.
associated with poverty and rural residence
not associated with AIDS, perhaps because of
leprosy's long incubation period
time of peak onset is in the second and third
decades of life
India and Africa, 90% of cases are tuberculoid
most severe lepromatous form of leprosy is
twice as common among men as among women
and is rarely encountered in children
Gram positive Obligate intracellular bacillus - due to its large
pool of non functional genes.
Acid fast stained with modified Fite stain or ZN stain
Occurs characteristically in clumps or bundles( “globi”)
Affinity for Schwann cells & cells of R-E system .
M. leprae grows best in cooler tissues (the skin, peripheral
nerves, anterior chamber of the eye, upper respiratory tract,
and testes), sparing warmer areas of the skin (the axilla, groin,
scalp, and midline of the back).
Optimal temp. for growth is 30-33 centigrade
M. leprae remains one of the few bacterial species
that still has not been cultivated on artificial
medium or tissue culture and produces no known
toxins, but can grow in
Nine banded armadillos(best)
Reservoir of infection
Main reservoir : Human being
Lepromatous case> Non lepromatous cases
Portal of exit
Major portal of exit : Nasal Mucosa
LL cases harbour millions of M. leprae in their nasal
mucosa discharged when they sneeze or blow nose.
Ulcerated or broken skin of bacteriologically
Mode of transmission
Transmission by inhalation
Droplet infection(most common)
Transmission by contact
Skin to skin contact with infectious cases
Contact with soil or fomites
Insect Vectors e.g.. Mosquito, Bedbugs
NB : Breast feeding and Transplacental infection do not
Long incubation period
Ranged: 2 to 40 years or more
Average: 3-5 years
Generation time : 12 days(1 day and 20 min for M.
tuberculosis and Escherichia coli, respectively)
Infectivity : Leprosy is a highly infectious disease with low
pathogenicity. Among household contacts of lepromatous
cases about 5 to 12 percent is expected to show signs of
leprosy within 5 yrs.
The bacterium's complex cell wall contains large
amounts of an M. leprae–specific phenolic glycolipid
(PGL-1), which is detected in serologic tests.
The unique trisaccharide of M. leprae binds to the basal
lamina of Schwann cells; this interaction is probably
relevant to the fact that M. leprae is the only bacterium
to invade peripheral nerves.
Leprosy affects all age groups but incidence generally
rises to a peak between 10 to 20 years of age and then
Higher incidence is seen in males, more marked among
adults, more marked among lepromatous cases.
Cell Mediated Immunity is responsible for resistance to
infection with M.leprae. In lepromatous leprosy there is
complete breakdown of CMI.
Indian Classification : clinicobacteriological
Madrid Classification : clinicobacteriological
Ridley Jopling classification : immunohistological
Classification by WHO Study Group on Chemotherapy
of Leprosy : clinicobacteriological.
Ridley- Jopling 1966
Most widely accepted
Divides Leprosy cases into five groups according
to their position on an immunohistological scale.
It can be used only when full research facilities
are available :
Borderline Tuberculoid (BT)
Borderline Borderline (BB)
Borderline Lepromatous (BL)
Pure neuritic type
Immunity in leprosy
LLHD BLHD BBHD BTHD TTHD
state, few lesions due
to high immune
LL - multibacillary state with
multiple lesions due to low
Borderline forms (BB, BT and BL) lie between these
two poles and are immunologically unstable, tending
to move towards one of the polar forms
Clinical Feature on
Including macular flat
lesion, papules & nodules
1 to 5 lesion
Definite loss of
BI <2 at all sites in the
initial skin smear
More than 5 lesion
Loss of sensation
may or may not be present
BI >= 2 at any site in the
initial skin smear
W H O classification
(For chemotherapy – M. leprae)
Indeterminate - I
Tuberculoid – TT
Borderline Tuberculoid – BT
If any of these have positive
bacterial index they should be
classified as multibacillary
for multidrug therapy
Mid borderline – BB
Borderline Lepromatous –
Lepromatous – LL
All smear positive cases
Earliest & transitory stage
One or two vague hypopigmented macule with definite
If untreated may progress towards tuberculoid,
borderline or lepromatous leprosy
Spontaneous regression may occur
less severe end of the spectrum
encompasses TT and BT disease
symptoms confined to the skin and peripheral
most commonly affected are the ulnar, posterior
auricular, peroneal, and posterior tibial nerves
TT leprosy is the most common form of the
disease encountered in India
Single or a few lesions
Asymmetrically distributed on trunk and limbs
Sharply defined, dry, flat or raised, erythematous or
hypopigmented, and are anesthetic.
One or two nerves may be enlarged near the skin
SS for AFB: Negative
Lepromin test may be strongly positive
Four or more lesions, asymmetrically distributed
Macules or plaques of variable sizes with well or ill-
defined margins & satellite lesions
Peripheral nerves enlarged asymmetrically
SS for AFB: may or may not be positive.
Lepromin test may be weakly positive
Intermediate between BT- and LL-type lesions;
ill-defined plaques with an occasional sharp
margin; few or many in number
Hypesthetic or anesthetic skin lesions; nerve
trunk palsies, at times symmetric
Multiple erythematous macules & plaques
Various sizes and shapes with punched out center and
ill defined slopping outer margin
Tend to be symmetrical
Nerves may be asymmetrically enlarged
SS for AFB: seen +/-
Lepromin test-usually negative, may be doubtful
Numerous, symmetrically distributed lesions
Hypopigmented or erythematous irregularly shaped
maculopapular, infiltrative nodules, or plaques, with
smooth surfaces & ill defined borders, sloping outwards
Nerves may be symmetrically or asymmetrically enlarged
SS for AFB: numerous seen
Lepromin test -negative
Numerous macules, plaques, nodules or diffusely
infiltrated lesions, shiny, smooth, symmetrically
distributed on face (leonine facies), trunk and
extremities with ill-defined margin which may be
slightly hypopigmented or erythematous
Symmetrical nerve enlargement is seen
SS for AFB: numerous seen
Lepromin test - negative
Diffuse thickening of the skin, with loss of hair
(eyebrows and eyelashes) : madarosis.
Saddle nose deformity
Clinical, Bacteriologic, Pathologic, and Immunologic
Spectrum of Leprosy
Feature Tuberculoid (TT, BT) Leprosy Borderline (BB, BL) Leprosy Lepromatous (LL) Leprosy
Skin lesion One or a few sharply defined
annular asymmetric macules or
plaques with a tendency toward
central clearing, elevated borders
Intermediate between BT- and
LL-type lesions; ill-defined
plaques with an occasional sharp
margin; few or many in number
Symmetric, poorly marginated,
multiple infiltrated nodules and
plaques or diffuse infiltration;
xanthoma-like or dermatofibroma
papules; leonine facies and
Nerve lesion Skin lesions anesthetic early; nerve
near lesions sometimes enlarged;
nerve abscesses most common in
Hypoesthetic or anesthetic skin
lesions; nerve trunk palsies, at
Hypoesthesia a late sign; nerve
palsies variable; acral, distal,
symmetric anesthesia common
BI(Bacteriological index) 0-1+ 3-5+ 4-6+
lymphocytes 2+ 1+ 0-1+
Macrophage differentiation Epitheloid Epitheloid in BB,usually undiff
but may have foamy changes in
Foamy change is the rule,may be
undifferentiated in early lesions
Langhans giant cells 1-3+ - -
Lepromin skin test +++ - -
Lymphocyte transformation test Generally positive 1 to 10 1 to 2
CD4 : CD8 ratio 1.2 BB(NT),BL:0.48 0.50
PGL1 antibodies 60 85 95
Eye : The anterior chamber can be invaded in LL with
resultant glaucoma and cataract formation.
Testes : May be involved in LL with resultant
Systemic involvement – Respiratory, Bones, Kidneys,
Lymph glands, etc.
M. Leprae : superficial nerve involvement
Neural involvement leads to muscle weakness, muscle
atrophy, severe neuritic pain, and contractures of the
hands and feet.
Ulnar nerve at elbow is most commonly involved , least
common is radial.
Most common cranial nerve involved is Trigeminal.
>30 percent neural loss required for loss of sensation.
First sensation to go is thermal (cold>fine touch).
Proprioception is usually preserved.
S Sole anesthesia
M Claw Toes
A Dryness in sole
History should include the following points :
Patients Bio data : name, age, sex, address
Family history of leprosy
Contact with leprosy cases
Previous history of treatment for leprosy, if any
Physical examination should include :
A thorough inspection of the body surface(skin).
Palpation of commonly involved superficial nerves:
1. Ulnar N. near the medial epicondyle.
2. Greater Auricular N as it turns over SCM muscle.
3. Lateral Popliteal N.
4. Dorsal branch of Radial N.
Testing for :
1. Loss of sensation : heat, cold, pain, touch .
2. Paresis or paralysis of muscles of hands and feet.
This includes :
Skin Smears :
Nasal Smears or blows :
Nasal Scrapings :
Bacterial index is the only objective way of monitoring
benefit of treatment.
According To Ridley’ Logarithmic Scale It Ranges
From 0 To 6+ and is based on the no. of bacilli seen in
an average microscopic field.
B 0 stands for no bacilli in any of 100 oil immersion
The MI is calculated after examining 200 pink-stained
free standing bacilli.
The percentage of solid staining bacilli in a stained
smear is referred to as MI.
It is a valuable indicator of the patient’s response to
treatment during the first few months and helps to
signal drug resistance.
SOLID FRAGMENTED GRANULAR(SFG)
PERCENTAGE : similar to MI but a more sensitive
indicator of the patient’s response to treatment.
Only certain way of identifying M. Leprae.
10 times more sensitive at detecting the bacilli than slit
Time consuming : requires 6 to 9 months.
Used for :
1. Detecting drug resistance.
2. Evaluating the potency of anti-leprosy drugs.
3. Detecting the viability of bacilli during treatment.
Newer in vitro macrophage culture which takes only 3 –
Reliable test for detecting at an early stage peripheral
nerve damage due to leprosy.
Method : carried out by injecting 0.1ml of a 1:1000
solution of histamine phosphate into hypopigmented
patches or in areas of anesthesia.
Result : in normal person it gives rise to a wheal
surrounded by erythematous flare(Lewis triple
response). In case of leprosy where the nerve supply is
destroyed, flare response is lost.
Particularly useful in cases of indeterminate leprosy.
Usually resorted to when there is high clinical
suspicion but the other test are unyielding. It also
gives information about the bacterial content of
Tests for cell mediated immunity(CMI)
Tests for humoral antibodies(serological tests)
FLA-ABS test : used for detecting subclinical infections. 92.3
percent sensitive and 100 percent specific in detecting specific
antibodies in all types leprosy irrespective of type and duration of
Others : RIA, ELISA.
Method : it is performed by injecting 0.1ml of lepromin
into inner aspect of the forearm. The reaction is read at 48
hours and 21 days. Two types of reaction have been
EARLY REACTION(FERNANDEZ REACTION) :
an inflammatory reaction develops within 24 to 48 hours and this
tends to disappear in 3 to 4 days. If the diameter of the red area is
more than 10mm the test is considered positive. It is a delayed type
hypersensitivity reaction to soluble constituents of lepra bacilli and
indicates whether or not a person has been sensitized by exposure
to and infection by lepra bacilli.
LATE REACTION(MITSUDA REACTION) : It is
characterized by the appearance of a nodule which
becomes apparent in 7 to 10 days and reaches its
maximum in 3 to 4 weeks. The test is read at 21 days. If
the nodule is more than 5 mm it is considered positive. It
is induced by the bacillary component and indicates cell
In the first six months of life most children are
BCG vaccination is capable of converting lepra reaction
from negative to positive.
VALUE OF LEPROMIN TEST :
Useful tool for evaluating the immune status of leprosy patients.
Aid to classify the type of disease.
Estimating the prognosis
Strongly positive in a typical tuberculoid case and getting weaker
towards the lepromatous end, the typical lepromatous case being
lepromin negative indicating failure of CMI.
The greatest drawback being high false positive and false negative
cases hence not used as a diagnostic test.
OTHER TESTS FOR CMI :
Lymphocyte transformation test(LTT)
Leucocyte migration inhibition test(LMIT)
In the absence of effective primary prevention by a
leprosy vaccine leprosy control is based on effective
multidrug chemotherapy(secondary prevention).
To interrupt transmission of infection
Early detection and treatment of cases to prevent deformities
To prevent drug resistance
First line drugs : rifampicin, dapsone, clofazimine,
ethionamide and prothionamide.
Second line drugs : quinolones, minocycline,
WHO RECOMMENDED REGIMENS OF
Rifampicin : 600mg once monthly under supervision
Dapsone : 100mg daily self administered
clofazimine : 300mg once monthly under supervision
50mg daily self-administered
Where clofazimine is unacceptable due skin coloration it may
be substituted by 250 to 375mg daily dose of ethionamide or
The above regimen needs to taken for 12 months within 18
WHO RECOMMENDED REGIMENS OF
PAUCIBACILLARY LEPROSY :
The above regimen needs to be taken for 6months within 9
Important points :
MDT is not contraindicated in patients with HIV
MDT is safe during pregnancy.
Drugs are excreted in breast milk but no reports of
adverse reaction except for mild discoloration of infants
skin by clofazimine
Leprosy is exacerbated during pregnancy, it is
important that MDT is continued
Rifampicin : highly bactericidal, a single 1500mg dose
kills 99 percent of viable organisms
Toxic effects includes anorexia, nausea, vomiting,
abdominal discomfort and orange discoloration of body
secretions. It is hepatotoxic
Dapsone : weakly bactericidal.
Adverse effects include hemolytic anemia,
methemoglobinemia, agranulocytosis, hepatitis,
neuropathy, psychosis and rarely…
DDS syndrome ch. by fever, maculopapular rash,
enlarged lymph nodes, hepatitis and exfoliative dermatitis.
Clofazimine : was originally synthesized for TB. Less
effective than dapsone but has added advantage of
preventing lepra reaction. More expensive but less toxic
which includes dark red discoloration of skin, mucus
membranes, sweat and urine.
Ethionamide and Prothionamide : highly bactericidal
killing 98 percent of viable bacilli in 3 to 4 days. Relatively
more expensive and more toxic.
During the course of leprosy, immunological mediated
episodes of acute or subacute inflammation known as
reaction may occur.
There are two types of reactions :
Type 1 or Reversal reaction
Type 2 or erythema nodosum leprosum
Both types can occur before the start of MDT, during
treatment or after completion of treatment.
occur in almost half of patients with borderline
forms of leprosy but not in patients with pure
Manifestations include classic signs of
inflammation within previously involved
macules, papules, and plaques and, on occasion,
the appearance of new skin lesions
nerve trunk most commonly involved in this
process is the ulnar nerve at the elbow, which
may be painful and exquisitely tender
most dramatic manifestation is footdrop, which
occurs when the peroneal nerve is involved.
(less commonly) fever—generally low-grade
type 1 lepra reactions precede the initiation of
appropriate antimicrobial therapy, they are
termed downgrading reactions, and the case
becomes histologically more lepromatous
when they occur after the initiation of therapy,
they are termed reversal reactions, and the case
becomes more tuberculoid
often occur in the first months or years after the
initiation of therapy
ERYTHEMA NODOSUM LEPROSUM
In ENL new inflamed, red nodules appear under the
skin, while the original lesions remain same. Commonly
on face, arm and legs & bilaterally symmetrical. They
appear in crops and subside within few days even
It is antigen antibody reaction.
Seen in MB cases only.
Nerves may be affected but is uncommon
Other organs like testis, eye, kidney may be affected
General symptoms of fever, joint pain, red eyes and
watering may be associated.
occurs exclusively in patients near the
lepromatous end of the leprosy spectrum (BL-
90% of cases it follows the institution of
chemotherapy, generally within 2 years
most common features of ENL are crops of
painful erythematous papules that resolve
spontaneously in a few days to a week but may
recur; malaise; and fever
may also experience symptoms of neuritis,
lymphadenitis, uveitis, orchitis, and
glomerulonephritis and may develop anemia,
leukocytosis, and abnormal liver function tests
Elevated levels of circulating tumor necrosis
factor (TNF) have been demonstrated in ENL;
thus, TNF may play a central role in the
pathobiology of this syndrome
thought to be a consequence of immune
Because of high risk of permanent nerve damage
reversal reaction needs to be promptly diagnosed and
Standard 12 wk. regimen of prednisolone is the
treatment of choice.
ENL varies in severity, duration and organ
involvement, and can be treated with prednisolone as
Treatment includes bed rest, splinting of affected
nerves, analgesics and prednisolone.
Prednisolone regimen Add clofazimine in ENL
40mg daily for first 2 weeks
30mg daily or week 3 and 4
100mg tds x 4 weeks
20mg daily for week 5 and 6
15mg daily for week 7 and 8
100mg bd x 4weeks
10mg daily for week 9 and 10
5mg daily for week 11 and 12
100mg od x 4 weeks
For neuritis, treatment with prednisolone
Should be prolonged to four weeks from
For pregnant women prednisolone should be started at
30mg dose instead of 40mg and limit the course for
10weeks in PB cases and 20 weeks for MB cases.
For children dose should be started at 1mg/kg of body
wt. per day.
Thalidomide : was reintroduced for the treatment of ENL,
mainly because of its antipyretic action. WHO does not
recommend the use of thalidomide in leprosy. Prednisolone is
more effective in controlling ENL and associated neuritis,
clofazimine is the drug of choice for the management of
chronic, recurrent ENL reactions. Another drug claimed to be
useful in ENL is pentoxyfylline.