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LEPROSY
(Hansen’s Disease)
Definition
• Chronic mycobacterial infection
• Peripheral nervous system,skin, other tissues
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Naturally acquired leprosy
- Chimpanzee
- Mangaby monkey
- Armadillos
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Epidemiology
• Mycobacterium leprae
• I.P. - (variable) 2-7 years
• At Risk population
Adults (less) - 5% conjugal
Children (more) - 60% in family
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PREVALENCE
Total No. of cases - < 3.5 million
Approx. 50 % - IN INDIA
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Mode of transmission
- Prolonged intimacy
- Respiratory - Droplet
- Skin to skin contact
- Tattooing
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Bacteriology
M.leprae (1873) - Hansen
• Non-culturable
• Acid-fast/alcohol fast
(5% H2SO4, 3% HCl decolorize)
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• Straight – Slightly curved rods
• Rounded ends
1-8 m long
0.3 m diameter
• Obligate intracellular- GLOBI
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Bacteriological index
• Density of bacilli in high power field
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No bacilli in 100 fields
1-10 bacilli in 100 fields
1-10 bacilli in 10 fields
1-10 bacilli in an average field
10-100 bacilli in an average field
100-1000 bacilli in an average field
>1000 bacilli in an average field
BI-0 BI-1 BI-2
BI-3 BI-4 BI-5 BI- 6
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Morphological index
• % age of presumably live bacilli
• Solid staining - live
• Granular staining - Dead
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Culture
• Non-culturable
• Hind foot pad of mice
• Armadillo
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PATHOLOGY
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Disease of PNS
• Target organ -Schwann cell
• Secondary -Skin (prefers cool areas)
Other organs- Eyes
- Reticulo-endothelial system
- Nose, pharynx, larynx, trachea
- Endothelium of small blood vessels
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- Arrector pilorum, dartos
- Skeletal muscles
- Testes
Female reproductive system is spared
- Spinal cord, CNS - Never involved
- CMI - AMI – Ig (Nonprotective)
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RIDLEY – JOPLING SCALE
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Lepromin Test
• Lepromin A
- Autoclaved suspension of Armadillo tissue
• Lepromin H
- Human tissue
Non specific
Not diagnostic
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Uses
• To ascertain CMI against M. leprae
• Indeterminate leprosy
• To investigate contacts / high risk
• To classify pure neural disease
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Fernandez reaction
Early - 48 hours
Mitsuda reactionLate - 4-5 weeks
LeprominPositive - TT, BT
Negative - BB, BL, LL
Variable - Indeterminate
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Classification
RIDLEY JOPLING
TT, BT,BB - Epitheloid cell granuloma
Giant cells
BL, LL - Foamy macrophages
Lymphocytes (Lepra cells)
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CLINICAL ASPECTSTuberculoid leprosy
TT (Localized)Hypopigmented
Hypo aesthetic/anesthetic
Macule / plaque
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Hypopigmented
Hypo aesthetic/anesthetic
Macule / plaque
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•Usually single/ (1-3 )
•Variable size
•Dry, scaly
•Hair loss
•Absence of sweating
•Absence of triple response
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• Nerve feeding the area
- Enlarged
- Irregular
- Cord like
- Nodular
- Abscess formation
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• AFB
Skin -negative
Nasal smear -negative
• Lepromin -Strongly positive
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Secondary changes
- Paralysis of nerve
- Muscular weakness
- Wrist drop
- Foot drop
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- Loss of sensation beyond lesions
- Trophic ulcers
- Spontaneous blister
- Osteomyelitis
- Lepra reaction
- Pain (Neuralgia)
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BORDERLINE TUBERCULOID (BT)•3 -10, variable size
•Hypo- pigmented, Hypo- aesthetic
•Loss of hair, sweat
•AFB
Skin - Absent / scanty
Nasal smear - Negative
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• AFB
Skin - Absent / scanty
Nasal smear - Negative
• Lepromin - Weakly positive
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• Secondary changes
-More common
- Immunological instability
- Reactions
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MID BORDERLINE( BB)
• Lesions >10
• Variable size
• Erythematous shiny plaques
• Loss of hair, sweat
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SATELLITE LESIONS
Reactions/Secondary changes
- Motor- Sensory
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• Punched out
lesions (annular)
• Inverted saucer
shaped (Swiss cheese)
•
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• AFB
- Skin - Moderate
- Nasal smear - Negative
• Lepromin - Negative
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BODERLINE
EPROMATOUS
Large no.of lesions
Papules & nodules
Plaque (less defined)
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ffuse areas of infiltration
ace, Hands, feet,Ear lobes
symmetrical thickening of ripheral nerves
ove - stocking anesthesia
ome areas of skin still ared
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Hair
Minimal loss over lesions
oss more in nerve distribution
AFB
-Skin -Many
-Nasal -Usually negative
Lepromin - Negative
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•Secondary changes
-Reactions
-Deformities
-Motor palsies
-Sensory loss
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EPROMATOUS
EPROSY
Diffuse infiltration of skin
Widespread lesions,
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ar lobe infiltration
eonine facies
o plaques
apules & nodules), rarely macules
erves symmetrical arged
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Glove & stocking anaesthesia,icthyosis
B/L madarosis
- Ciliary
- Superciliary
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Hair/ sweat - not affected
AFB
-Skin Globi &clumps 6 (+)
-Nasal
Lepromin - Negative
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YSTEMIC FEATURES
Epistaxis,nasal stuffiness,saddle nose
B/L pedal edema
Eyes - Iridocyclitis
Bones -
eriostitis(Hand/Feet/Skull)
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Testes - Atrophy
- Acute epididymo-orchitis
Kidney - Amyloidosis,
Glomerulonephritis
Lymphadenopathy
Lepra reaction type II
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NERVE INVOLVEMENT IN LEPROSY
ERIPHERAL NERVES
Supraorbital & supra trochlear N
Infraorbital & infratrochlear N.
Supra clavicular N.
- Lateral,Middle,Medial
Greater auricular N
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Radial N. & Radial cutaneous Br.
Ulnar N
Median N
Lateral,medial & intermediate
cutaneous N. of thigh
Lateral popliteal N
Post tibial N
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CRANIAL NERVESOlfactory nerve
Fifth nerve
Seventh nerve(Facial)
- Zygomatic branch
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acial N palsy
LMNP
Most commonly
with lesion over face
Lepra reaction
Bilateral in few
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NDETERMINATE
EPROSYmmunity
- Not defined
Few hypo-pigmented
macules
Anesthesia +
Nerves +
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• Smear -ve
• May heal spontaneously
• May evolve as BB, BL, LL, BT
• Lepromin - Variable
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LEPRA RACTIONSHypersensitivity states
Type I - Delayed type hypersensitivity
(CMI)
Type II - Immune complex mediated
(ENL)
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TYPE I LEPRA REACTION
Without treatment
TTBT BB BL LL
----------------With treatment
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• Regain of CMI
• On treatment -about 6 months
• BB, BT
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• Clinical Features
- Swelling, erythema, ulceration
- Lesions
- Acute Neuritis
- Paralysis, Neuralgia
- Fever/malaise
- Rarely
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Treatment
Lepra I• Mild - NSAIDS
• Severe
- Systemic steroids
- Glucocorticoids
- Surgical intervention
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TYPE II LEPRA REACTION Erythema Nodosum Leprosum (ENL)• Immune complex deposition • LL,BL• No relation with treatment• May be presenting symptom
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linical features
Multiple system Involvement
kin
ENL : VASCULITIS
Bright erythematous,
tender, papule, nodule
plaques
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• Eye : Acute iridocyclitis
• Rhinitis, epistaxis
• Ac. Lymphadenitis - generalized
• Ac. Epididymo orchitis
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• Ac. Periostitis - Bone pains - tibia
• Ac. Myositis
• Ac. Glomerulonephritis
- Proteinuria
- Casts
• Ac. neuritis
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Factors precipitating Type 2
reaction
• Inter-current illness /Infection
• Injury, surgical intervention
• Stress -Physical / mental
• Montoux test - vaccinations
• Pregnancy - delivery
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TREATMENT
• NSAIDS
• Glucocorticoids - 1mg/kg body wt.
• Thalidomide - 100mg TDS
Clofazamine - 100mg TDS
Colchicine - 1.5-2.0mg daily
Chloroquine - 250mg TDS
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Diagnosis of Leprosy
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Investigations for diagnosis
• Slit skin smear - SSS
- BI
- MI
• Nasal smear
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• Skin biopsy
• Nerve biopsy
• Histamine test - axon reflex
• Sweating test
• Lepromin test
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For treatment & follow up
• HMG,LFT,RFT
• Urine R/E
• X-ray chest
• G-6-PD deficiency (if suspected)
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OTHERS
• Normocytic / Normochromic anaemia
• Biological false positive VDRL
• Rh factor, ANF, LE cells
• ESR
• Thyroglobulin Ab
• Anti spermatozoal Ab, Cryoproteins
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TREATMENT OF LEPROSY
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ANTILEPROSY DRUGS
First line drugs
Dapsone
Rifampicin
Clofazamine
Others :
Ethionamide
Thiacetazone
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DAPSONE(DDS)
Diamino–diphenyl sulfone
•Dihydrofolate synthetase inhibitor
•Bacteriostatic
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• 6-10mg/kg body wt./week
100mg OD >50kg
50 mg OD <50kg
• Half life - 28 hours
• Cheapest - Most effective,
safe in pregnancy
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SIDE EFFECTS
• Light headedness/headache
• Hemolytic anemia
• Agranulocytosis
• Hepatitis
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• Psychosis
• Fixed drug eruption
• Exfoliative dermatitis
• Methemoglobinemia
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CLOFAZIMINE
• Red iminophenazine dye
• Bacteriostatic
• Mechanism - unknown
• Anti-inflammatory action
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• Anti leprosy dose - 50mg/OD
• Anti inflammatory dose -100mg TDS
• Half life - 70 days
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SIDE EFFECTS•Reversible dose-related, reddish brown
discoloration of skin, hair,sputum, urine,
faeces
•Keratoderma - Acquired ichthyosis
•Phototoxicity, acneiform eruption
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•Abdominal syndrome
Early (1 month) :Diarrhoea/abdominal pain
Late (>3months): Diarrhoea /abdominal pain
- Loss of weight
- Death
- Deposition of CLOFAZIMINE
CRYSTALS
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RIFAMPICIN
•Potent bactericidal
•Inhibits RNA synthesis (DNA dependent
RNA polymerase)
•Dose-10mg/kg body weight
- Maximum 600mg/day
- 450mg <35 kg
•MI - 0 (5 weeks)
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SIDE EFFECTS
• Red discoloration of urine
• Intermittent administration.
a) FLU Syndrome -Fever, chills,rigors,bone/
joint pains, malaise,headache
b) Syndrome of shock, renal failure,
hemolytic anemia, purpura
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OTHERS
• Hepatitis
• Thrombocytopenia
• Psychosis
• Osteomalacia
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• Pemphigus vulgaris
• Steven Johnsons syndrome
• Porphyria cutanea tarda
• Drug interaction
-Induction of hepatic microsomal enzymes
(Steroids /oral contraceptive)
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TREATMENT REGIMEN
Classification for treatment purposes
Paucibacillary-Smear negative
(TT,BT)
Multibacillary -Smear positive
(BB,BL,LL)
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MULTI DRUG THERAPY : (MDT)
WHO
Need : Drug Resistance - Dapsone
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WHO MDT (PB)
Dapsone 100mg OD (Self administered )
Rifampicin 600mg once monthly
(Supervised)
Duration - 6 months
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Children (0-5year)
- Dapsone 25mg
- Rifampicin 300mg
(6-14 year)
- Dapsone 50mg
- Rifampicin 450mg
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WHO MDT (MB)
Dapsone -100mg OD (Self administered)
Rifampicin-600mg once monthly ( supervised)
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Clofazamine-50mg OD (self administered)
+ 300mg once monthly ( supervised)
Duration - 2 years
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NLEP MDT
PB - Same as WHO
MB - Intensive phase + WHO
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tensive phase
2 weeks daily - supervised
Rifampicin - 600mg
Clofazimine - 100mg x 14 days
Dapsone - 100mg
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Newer drugs
ClarithromycinOfloxacinMinocyclineRifabutinPefloxacinDapsone analogues
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REHABILITATION
• Cosmetic correction
• Profession adjustment
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REHABILITATION
• Cosmetic correction
• Profession adjustment
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