LEPROSY

Definition
• A mycobacterial infection cause by mycobacteriaum
laprae affecting primarily
- Skin
- Peripheral nerves
- Eyes
- Mucus membrane of upper respiratory tract
• Majority of world’s population is immune to this
bacillus. Transmission is airborne with droplets or
direct prolonged skin contact with untreated person
 EPIDEMIOLOGY
WHO estimation
• 2002 prevalence – 524, 311 people
• 2002 new cases – 620, 672 as reported by 110 countries
• 83% of leprosy patient live in
6 countries
– Brazil
- India
- Madagascar
- Mozambique
- Nepal
- Tanzania
• 2-3 million people have permanent disabilities
due to leprosy.
• Registered leprosy cases have increased from
5.4 million 1985 to 1 million 2001
• Goal of WHO decreased prevalence of leprosy
to 1/10,000 people nationally.
• WHO definition of leprosy case
– An individual with clinical and /or
pathological evidence of leprosy who has
not completed a full course of treatment
• Annual incidence of new leprosy cases remain
stable approximately 650,000- 685, 000
• Demographically, leprosy has bimodal age
distribution one Peak between 10-15 yrs, 2nd
peak between 30- 60 yrs
• On the whole children represent 15% of leprosy
cases and tend to have self healing lesions of
leprosy.
• Reservoirs
– Untreated multibacillary patients
– Paucibacillary patients
– Nine –banded armadillos in South Central
USA
– Chimpazee in Sierra Leone
– Sooty mangabey monkey in Nigeria
• Incubation period for leprosy ranges from few
months to 5 years, incubation period of 20
years is reported
• > 95% of people are not susceptible to leprosy
even after significant exposure.
• There is impaired cell- mediated immune
response to M. leprae bacillus in individuals
who develop leprosy
• Studies have demonstrated the role of
genetics in susceptibility to leprosy.
- Human leukocyte (HLA) DEZ is associated with
tuberculoid disease.
-There is a region on chrom 10p 13 as the
susceptibility locus for leprosy.
- Chrom 6q 25 has a gene for susceptibility to
leprosy
-PACRG and PARK 2 genes are risk factors for
leprosy worldwide.
-These genes are expressed by schwann cells and
macrophages which are primarily host cells of M.
leprae
PATHOGENESIS
• M. leprae – an obligate intracellular rod with
multilayered cell wall.
- outer most layer contains phenolic
glycolipid – 1 (PGL-1) which mediate
the interaction with laminin 2 on
the basal lamina of schwann cell
axon of peripheral nerves and
denyelinate schiwann cell. Also M.
liprae directly invade the non-
myelinated schwann cells
• Host cell mediated immunity to M. liprae
correlates with clinical manifestation of the
disease.
- Tubercloid leprosy is characterized by strong cell
mediated immunity to M. liprae which controls
bacterial growth hence patients have localized
nerve involvement and few skin lesions.
- On the other hand, lipromatous patients lack cell
mediated immunity hence present with extensive
nerve involvement with numerous skin lesions
and uncontrolled bacterial replication.
- Histologically tuberculoid lesions have well
formed granulomas with CD4+ T. lympocytes
occupying central core of granuloma while
periphery are CD 8 cells
- lepromatous pole has diffuse granlomatous
inflammation and contain most CD8 cells.
Cytokines
- Tuberanloid lesions express Th1 cytokines (IL-2, IL -12
interferon –y) which activates macrophages and
circulating monocytes fostering granulomatous
response against M. leprae.
- Lepromatous lesions express Th2 cytokines (IL-4,IL-10)
which impaire cell mediated immune response and
starts a strong humoral response hence significant
antibody production.
NB.
• Signaling lymphocyte activation molecule
(SLAM) increases interferon- y production
• Granulysin, an antiumicronial protein.
Released by CD4+ T cells plays a role in defense
against leprosy
• Toll-like receptors (TLRSs) expressed in
schwann cells in tuberculoid lesions are part of
the innate immune defense against M. liprae.
• Activation of TLR2 with M. leprae lipopetides
triggers apoptosis of schwann cells thus a
mechanism which activates immune response
but also contributes to nerve damage in
leprosy.
 Clinical features
• Clinical manifestations of leprosy are found in
– Skin
– Peripheral nerves
– Mucus membrane of upper respiratory tract
– Anterior segment of eye tests
• Skin lesions – main clinical.
Presentation commonly seen on
- Buttocks - face
- Thighs - trunk
- Lateral aspect of extremities
• NB M. liprae likes cooler areas of the body e.g
peripheral nerves in face, neck and limbs.
• Nerve damage develop before diagnosis during
treatment or after complication of adequate ABS
therapy
• Most people are resistant ro M. leprae those who
develop the disease start with the indetermin
form where the majority of cases resolve the
individual develop one of the types of leprosy
depending on the body of the M. leprae
• Tuberculoid TB BB lepromatous
BL (extensive
skin disease with systermic manifestations)
• Ridley – jopling classification of leprosy
 – Based on
• Clinical features
• Bacterial index
• Histopathology findings
• Individuals cell medicated immunity to M. leprae
Ridle - jopling 1962

TT BT Borderline Borderline Lepromatous

Tuberculoid Borderline Borderline Lepromatour
BB BL
• WHO 1980

Paucibacillary Multibacillary

Note immaturity of borderline patients is

unstable. If immaturity improves borderline
patients moves towards tubes culoid end and
patient experiences
Type 1 reaction.
If immunity weakens patient shift towards
lepromatous type with a down grading reaction.
 Inderterminate leprosy
• Presents with one or a few ill defined
• macules - lympopiguiented in dask skin
individuals or erythematous
• Lesion is amhidrotic, sensation intact and no
nerve involvement.
• Resolve spotaneously and in a few go to
Ridley-Jopling spectrum.
• Select good Bx site and do serial histological
section. Study in order to classify.
Histologically, there is minimal inflammation
around skin adnexae with selective infiltration
of nerve bundles of inflammatory cells.
• Slit smears are typically negative and bacterial
index 0.
 Tuberculoid leprosy
• Cell mediated immunity against M. leprae is
high.
• Fewer (< s) asymmetrical skin lesions on face,
trunk and buttocks
• Lesion is solitary, lympopiguented
• Shortly defined plaque with a raised border
central portion may be erythematous or
lympoguituted and scaly, lesions are
anaethetic and have absence of hair
• There is early loss of sweating due to
disturbances in antonomic intervention.
• Histologically are well formed epitheliod cell
granulomas with langhan giant cells
surrounded by dense infiltrate of lyphocytes
around nerve bundles, neuro vascular bundles
and sweat glands.
• Nerve bundles massively enlarge in the deep
dermis therefore Bx skin samples should be
deep enough to get a dispose tissue.
• Bacterial index on slit smears is 0 or 1
 BORDERLINE (BT,BB,BL)
• In borderline tuberculoid patients have anaethetic
discrete plaques similat to TT
• There are multiple lesians >5< 10 large less well defined
with statelite papules
• Several peripheral asymetrical nerve trunks enlargement
with neuropathy
• Bacterial index 0-2
• In borderline borderline patientshave numerous
asymmetrical annular plaques.
• Lesians have features of both TT and LL
• Systemetrical or asymmetrical nerve
lyphertophy or neuritis
• Bacterial index is 3 to 4
• In borderline lepromatous
– May have dimophic lesions symmetically and
bilaterally distributed and with widespread small
mucules, papules and molecules of various sizes
and shapes.
• Widespread asymmetric nerve involvement
• Bacterial index is 4 to 5
Hallmarks in histology classification
a) Langhans cells present in TT and BT
b) Vacuolated giant cells present in BB and LL
c) Epitherliod cells present in TT, BT and BB
d) BB to LL
a) Histiolcytes and foamy macrophages present
in BL and LL
b) Dense non specific inflammatory infiltrates in
TT although a few in BL
c) Subpidermal zoning is preserved from
d) Lamination of perinerium is present in BL and
LL
 Lepromatous leprosy
• Absence of the cell –mediated immunity in LL,
M. leprae proliferate freely resulting in
widespread systematic disease.
• Initial skin lesions are erthematous lympho
pigmented diseminated small mascules with
poor borders
• Peripheral nerve damage occurs late therefore
sensation intact
• With disease progression many lesions are
infiltrate including ear helices and ear lobes
may become pendulous loss of lateral eyebrows
and at times eye lashes (madorosis)
• Bacterial infiltration of facial skin causes the
classic leonine face appearance and in
advanced index LL patients have a glove and
stocking neuropathy
• Claw-finger and deformalities
• Invasion of nasal mucosa causes
– Nasal stuffiness with increased secreation and
epistatis and epistaxix
– Destruction of nasal cartilage and intrinsic nose
bone- perforation of nasal septum hence “saddle-
nose deformity”
– Miltrogan invasion by bacilli occurs
– Lesions in oral mucosa including palate and
tougue
– Vocal cord oedema causing hoarseness
– Occurs in liver, spleen, testes, bone marrow and
lymph nodes.
– In fact there may be bony collapse of metatarsal
head and neck
– Ulcers of the hands and feet with 20 infection –
osteomyelitis
– Testicular invasion may produce atrophy, sterility
and gynaecomastia.
– Glomerulophritis due is immune complexes
• Histology LL reveals a clear Grenze zone 1.1
epidermis and the granulomas in the dermis.
The grannulas compose aggregates or sheets
of foamy macrophages with sparse
lymphocytic component.
• Foamy macrophages are called viclous or
laprae cells loaded with M.lepra bacilli
• Acid fast staining reveals numerous bacilli
disperesed or in clusters called globi
• Bacterial index is 5-6
• may present as histoid leprosy in with skin
lesions consist of firm, non tender consist of
firm non tender dermato fibroma- like papular
and nodules
 Eye diseases (ocular manifestations )
• In TT, ocular manifestations are due to invasion
of nearby nerves
• Specifically trigminal nerve causing
a) Increased spotaneous blinking
b) Unaware of dryness FB and injuries
c) Facial nerve involvement causes
d) Motor weakness or parylysysis of the
orbicularis oculi muscle, with inability to blink
forcefully and logophalmos
b) Loss of protective blinking leading to dry eyes,
kesatitis caused by injury or infection.
• In LL leprosy (two of bacterial immune
complexes)
– Blood borne M.leprae invades the cooler as of the
eye including cornea episclera, sclera, conjunctiva,
– Ciliary body and iris
– Invasion is asymptomatic and visible after 4 years
of on set.
• Cornea apacitities and decreased vision
• Scalera and iris episcerrities, asceritis
and iridocyclitis.
• Iridocyclitis causes contaract glaucoma and
blindness
• Use of corticosteroids (topical or systematic)
causes subcapular posterior contaracts in
leprosy patients.
• Invasion of nasolacrimal duct causes increase
or decrease in tearing dacryocystitis
 Management of complications
• Hand and Foot injury
– Damage occurs due to peripheral motor and
sensory neuropathy
– M.leprea rarely invades tone injury is due to loss
of slusation there is also ulceration of chronic
infection e.g osemyelitis
– Skin dries up and tissues provide entry of bacteria
– Injured or infected limbs are continuously used
because absence of sensation.
• Pregnancy in leprosy
– Child bearing mothers should avoid pregnancy
precipitates first symptoms of leprosy- neuritis,
erythema nodosum leprosum
– Reverse reactions more common during
postpatum period when mother’s cell mediated
immunity is just recovering at this time.
• Reactions in Leprosy
– 4 reactions complicating leprosy and occuring in
25- 50% of patients
• Type 1 reversal reaction
– Occurs in borderline patients (BT, BB, BL)
– Represents an acute increase in cell mediated
immunity against M. leprae
– Commonly referred to as upgrading reaction.
• Type 2 reaction
– is erythema nodosum leprosum
(ENL)
- Occurs only in BL and LL patients and represents
an antigen - antibody immune complexreaction.
Down grading reaction
- Arises in untreated or non compliant patients
when they experience a shift of their immunity
towards LL
- Clinically patients present with new lesions, fevers
and malaise
• Difficult to distinguish them from patients
with type 1 reaction.
Locio’s reaction.
- A rare vasculitic reaction in patients with
untreated lucious leprosy (diffuse
lepromatous skin infiltration)
Note
a) Type 1 reversal reaction is a delayed – type
hypersensitivity react occurring within 1st 6-
12 after beginning therapy. Characterized by
acute inflammation due to upgrading of cell
mediated immunity.
Immunologically the reaction thought to be due
to a shift from Th 2 Th 1 T – cell response
• Clinically there is
– erythena
– Warmth
– Oedema of lesions, hands and test
– Pain or swelling in one or more peripheral nerves
b) Type 2 reaction
- M.leprae antigens and antibodies from
immune complexes deposited in
• Skin
• Blood vessel walls
• Nerves
• Other body organs
• Characterized by new crops of
– Thider
– Erythematous papules, plaques nodules and brillae
• There is fever
– Polyarthralgia
– Myalgia
– Malaise
– Neuritis
– Others rhinitis, epistaxis orchitis, protenuria and
hematuria.
NB immune complex glomerulonephritis rarely
develops.
b) Lucio’s phenomenon
- A diffuse nochlar form of lepromatous leprosy.
- Also known as la lepra bonita described in
1948 by latapi and chevez.
- It is a vasculitic reaction in un treated patients
characterized by tender purpuric lesion with
necrotize and ulcerate.
• Often restricted to extrimities but trunk can
be involved as well as leprae is ineffective
however the humoral immune system remains
intact and vast qualities of antibodies
produced respond to the overwhelming
amount of M. lepae antigens. It is the severe
immune complex reaction which causes
destructive vasculities and skin necrosis
• Diagnosis
Leprosy case is defined by WHO as an individual
who has to at least one of the following
- anaethetic skin lesion
- Thickned peripheral nerve
- Positive skin smears
Other defination
a person with one thickened nerve and either a
solitary hypopigmented skin lesion or a functional
neurologic impairment typical of leprosy.
Evaluation
a) Personal and family history of leprosy should
be elicited
b) Positive history of nasal bleeding
• Persistent nasal congestion
• Painful elbows
• Changes in sensation or motor function
• Areas of numbness
• Burning in the hands or feet.
• Recureulz ulcers or cellulitis of the hands extent
c) Physical examination focusing on skin and
peripheral nerves.
Examine
- Skin for hypopigmented or erythematous
anaethetic patches or plaques or areas with
increased sweating.
- Neurosensory testing can be done using a
cotton wisp
• Eyes examined for
– Pupil size
– Conjuctiva eryena
– Ability is close eye completely
NB patients with borderline or LL disease
should be refferred to an opthamologist for
ocular assessment.
- Nerves –pulpate peripheral nerves for
enlargment and tenderness particularly
• Greater auricular
• Ulcer
• Radial outaneous
• Posterior tibia
• Common peroneal
NB
Assess motor function relating to above nerves
Examine hands and feet for
- Muscle atrophy
- Ulcerations
- Claw hand deformalities
- Fools drop
- 20 infections
-
• examine tests for
– odema
– Molecules
Biopses
4mm- diameter punch treatment should be
performed at the active boarder of skin
lesion.
Skin smears
- To quantity bacterial load this helps to classify
patients disease.
Skin smear bacterial index
Very numerous +6 Over 1000 bacil/oil/immersion field

Numerous +5 100- 1000 bacilli mmersion field

moderate +4 10 – 100 bacilli mmersion field
Few +3 1-10 bacilli bacills/
Very few +2 1-10 bacilli/10 fields
Rare +1 1-10 bacilli/100 fields
None found NF No AFB seen on entire site
Differential diagnosis
• indeterminate leprosy
Different are
– vitiligo
- Pityriasis alba
- Post immatory hypopigmentation
- Pirita
• Do wood’s light exam to R/O vitilige
Tuberculoid and BT lesions are anaethetic
and can be distiguished from tinea corporis,
tinea faciale
other papullosquamous diseases include
- Psoriasis vulgaris
- Pityriasis rosia
- T-cell lymphomia parapsoriasis
- Lumpus erythematosas
other papullosquamous diseases include
- Psoriasis vulgaris
- Pityriasis rosia
- T-cell lymphomia parapsoriasis
- Lumpus erythematosas
- Syphilis
- Sarcoidosis
NB Sarcoidosis clinically present with indurated
skin lesions with non- caseating granulomas.
Reticulum staining of type III collagen
fiberdifferentiates 1.1 leprosy yet in sarcoidosis,
it is preserved.
PCR
- Detects M. leprae in treatment specimen of
patients suspected of leprosy.
- Negative results are got where bacilli are rare
even in established leprosy
Cases
- PCR is recommended in non endomic
population with presence of acid – fast bacilli
on microscopy and who have a typical
histopathologic and clinical features in
obscure diagnosis.
Others
- Madarosis of lateral 1/3 of eye brows is also
seen in thyroid disease.
- Peripheral neuropathy of multibacillars
patients must be differentiated from diabetic
neuropathy
• Do electronryelogran (EMG)
- In leprosy there is segmental slowing of nerve
conduction velocity of clinically involved
nerves.
- Peripheral sense thickening is also common in
rare conditions like - charcot marie - tooth
dose
- Dejerine – sottas disease
 Treatment
• Multidrug therapy (MDT) by WHO
1) Paucibacillary leprosy
a) Tabs Dapsone 100mg od x 6/12
b) Caps Ritampin 600mg monthly x 6/12
• 2) Pucibacillary with single skin lesion single
dose of
a) Ritampin 600 mg
b) Oflaxacin 400mg
c) Minocycline 100mg
Multibacillary under supervision
a) Caps Rifampin 600mg monthly for 12/12
b) Clofazimine 300mg monthly for 12/12
c) Tabs Dasone 100 mf (in combination with
clofazimine 50mg) monthly for 12/12
NHDP treatment Regimen
1) Pauncibacillary
a) Ritampin 600mg od x 12/12
b) Dasone 100mg od x 12/12
If neuritis developes clofazine is added.
2) Multibacillary
a) Rifampin 600mg od x24/12
b) Dapsone 100 od x 24/12
Alternative drugs in resistance
- Ofloxacin 400mg daily
- Levofloxacin 500mg daily
- Clarithromycine 500mg bd
Baseline laboratory monitoring
a) Glucose -6- dehydrogenase
b) CBC
c) Liver function tests
d) Urinalysis
Reversal reaction
1) Antipyretics and analgesics in mild reaction
2) Severe reaction
a) Preduisolve for 4- 6 months
3) Neuropathis pain
b) Gabapentin
c) Amitripty line
4) Chronic reversal and ENL reactions.
a) Increase dosage of clofazimine and in
combination with predn
b) Consider precipitating factors like pregnanc,
intestinal parasites, immuno- compromising
infections
5) Severe ENL
- Thalidomide
- Take caution in pregnancy, it is tetraglic
6) Caution in ISS patients for drug interaction
especially rifampin and ARVs especially
protease inhibitors.
TB patients should be aded to rimfapin
7) Supportive therapy
- Neurosensory evaluation periodically
- Orthopadeadic appliances
- Occupational therapy
- Frequent ophtjalmoplogy and neurology
consultations.
- Ulcers require wound case
8) Completion of therapy WHO recommends 2
year follow up for multi
a) BCG vaccination increases risk of developing
leprosy
WHO – Eye distability grading
G O- No eye lesion
C-1 – L+ eye lesion vision not affected better
than 6/60 WCF 6M
G- 2 – L+ poor vision was 6/60 or CF
- Large attachments
- Iridocyclinitis
- Canal opacity
- Ocular complications of leprosy
• Definition
A mycycobacterial infection caused by
mycobacterium leprae and primarly
Affects
- Skin
- Peripheral
- Eyes
- Mucous membrane of R/S
Diagnosis
1) Diagnosis is basically clinical an individual
with one of the following
- An anaethetic skin lesion thickened
peripheral nerve
- Positive smear
2) Biospes
4mm diameter purid Bx active boarder of lesion
3) Skin smears
- To quantity bacterial load.
Def – leprosy
Ocular manifestation are due to invasion of
near by nerves in the tuberculoid stage when
body immunity is high.
Trigeurinal nerve
- Increased spotaneous blinking
- Un awareness of dryness, TB or Injuries
- Ulceration and scarring that occurs because
protective corneal reflexes are damaged or
destroyed; causing corneal anaesthesia
Treatment-
• Examine eye regularly
• Water based lubricate ( mostly /cellulose
• Ointments.
Facial nerve
- Paralysis of orbicullaris oculi with inability to
forcefully blink
• Lagophthialmisis issues.
• Exposure keralitis also issues.
Treatment
• Lubricant drops
• Ointments
• In the lepromatous stage bacterial load is high
and body immunity very low or abituls and
with fornication of immune complexes.
• M. laprae invades cooler areas of the eye.
Conjunctiva
• Dryness of conjuctiva
Treatment
- Tropical steroids + ABS
Cornea
• Punctate kertilis
• 20 corneal ulceration and scaring
- Tropical ABS
- Corneal transplant
Iris and sclera
- Iritis
- Constricted pupil because dilactor muslce is
weak
• Whitish nodules (iris peals)
Complications
• 20 glancous
• Pupillary block
• iris boube
• increase fluid secreation
• plithisis bulbi
Treatment
- Local steroids + mydriasis, antiglucoma
Others
- Contatacts
- Treatment contaract surgery
- Loss of eye brows and eye lashes
- Called madrosis
- Usually symetrical and common in lateral part of
eyebrows.
• Treatment
Graft of hair skin from nape of nack
Skin changes
Facial skin (eyelids and brows)
- Diffusely thickened
- Inflamed
- Nodules
- Treatment- systemic with ABS
• Naso lacrimial cluds
• Often causes dacryo cytitis
• Treatment – probing syringing
- DCR