Leprosy

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LEPROSY

• DR. ALICE GWAMBEGU

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Leprosy

• Leprosy
• Synonym Hansens disease
• Named after Armauer Hansen, 1873, Norway
  Physician
• Definition
• Leprosy is a
• Chronically progressive,
• Slightly contagious, Granulomatous, infectious
  disease,
• Caused by Mycobacterium Leprae

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Leprosy

• Leprosy was considered
• A Scourge (curse) of mankind
• Patients have been ostracized/hated
• by their communities
• Because
• leprosy can be accompanied by very severe
  mutilations

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Severe mutilation
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Severe mutilation
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History

• Leprosy
• Leprosy is an age-old global disease
• Described in the literature of ancient
  civilizations
• Origin of leprosy still enigmatic
• According to current genetic studies of  M.
  leprae genome
• It appears, leprosy spread from Africa to the
  rest of the world
• It was Imported into Europe in 4th cent. BC by
• Troops of Alexander the great
• There were Special laws for lepers
• When crossing bridges!!!
• In Nepal Lepers still disinherited/disowned

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Epidemiology

• Global leprosy burden
• 127,558 new leprosy cases globally in 2020
• According to official figures from 139 countries
• From the 6 WHO Regions.
• This includes 8 629 children below 15 years
• New case detection rate among children was
• 4.4 per million
• Global prevalence is 16.7 per million population
• By the end of 2020

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Global burden

• Countries endemic for leprosy include
• India,
• Brazil,
• Indonesia,
• Mozambique,
• Madagascar
• Tanzania
• Nepal
• Tanzania under the
• National Tuberculosis and Leprosy Program

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Global distribution

• Occurrence
• Predominantly tropics and subtropics
• 40o N to 40oS
• BUT also in cooler regions Nepal, Korea
• An association with
• HLA B8
• and possibly
• HLA A9 has been described.
• Two factors are necessary for spread of leprosy
• Susceptibility of individual
• Possibly genetically determined
• Close prolonged contact with open cases

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Etiology

• Mycobacterium leprae is an obligate intracellular
  bacillus (1-8µm by 0.3-1µm)
• It is the first bacillus to be ass/with human
  disease
• Classified separate from other mycobacteria
  because failure to grow on artificial culture
  media

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Etiology

• More wide spread growth and disease in
  Immunosuppressed animals like mice
• Temperature favoring growth is 300 33o C
• Fastidious growth where growth cycle complete
  after 12 13 days (approx. 2 wks.)
• M. leprae has predilection for Schwann cells
• and Cutaneous macrophages

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Etiology

• M leprae produces no toxins
• It is the only bacterium that invades peripheral
  nerves
• The bacillus is well adapted to penetrate and
  reside within macrophages
• It may survive outside the body for months
• In the untreated patient only 1 of M leprae are
  viable

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PATHOGENESIS

• Route of transmission?
• Not known with certainty
• However, disease occurrence requires long and
  close contact with open case
• i.e. direct transmission by air is not
  possible!!!!
• Nasal droplet/Nasal secretions widely believed
  but grossly disputed
• In tropics Insects e.g. Flies, bugs, fleas seem
  to play an indirect role but not clearly
  documented

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Pathogenesis

• Primary lesion or primary complex as in TB?
• Is unknown
• There is no atypical mycobacterium leprae
  infection
• Sites of predilection for Myco leprae cooler
  parts
• Skin
• Peripheral nerves (in Schwann cells)
• Mucous membranes
• Upper respiratory tract

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Pathogenesis

• Leprosy Tissue damage
• Principal mechanisms of tissue damage
• Cell mediated Immunity (CMI)? Degree to which is
  expressed
• Humoral immunity Damage extent determined by
  bacillary spread, multiplication, antibody
  production
• Immunological complications Lepra reactions
• Nerve damage and its complications trophic ulcer
  etc

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Degree of CMI expressed

• For Strong CMI individuals
• Bacillary spread is limited to one or few sites
  in the skin and peripheral nerves
• This leads to TUBECUOID leprosy (pause bacillary
  leprosy)
• However
• Extensive Lymphocytic neural infiltration occurs
  which rapidly causes nerve damage

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Degree of CMI expressed

• For Weak/Absent CMI indivivuals
• Extensive bacillary spread and accumulation of Ag
  in infected tissues
• There is slow and gradual nerve infiltration and
  nerve damage
• This leads to Lepromatous leprosy
• Between these two polar forms
• Lies the rest of the spectrum of leprosy (BL,
  BB, BT)

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Strong CMI Tuberculoid leprosy
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Weak CMI There is Humoral immunity
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Humoral immunity

• Humoral immunity found in Lepromatous Leprosy
• Due to weak or absent CMI bacilli spread
  extensively via the blood stream to all cool,
  superficial, tissues of the body i.e.
• eyes
• Upper respiratory mucosa
• testes
• superficial muscles and bones of hands, feet and
  face and
• Peripheral nerves
• Skin

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Immunological complications

• Lepra reactions
• Occur as the immune response develops
• The antigenic stimulus from bacilli varies esp.
  in BL
• Reaction occurrence depends on spectrum of
  Leprosy which consists of
• True Tuberculoid (TT) leprosy
• Borderline Tuberculoid (BT) leprosy
• True Borderline (BB) leprosy
• Borderline Lepromatous (BL)
• True lepromatous (LL)

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Immunological complications lepra reactions

• Type I Reaction is encountered in pts with
  unstable leprosy i.e. BT, BB, BL
• Two types of presentation
• Upgrading or reversal reaction
• Gain in CMI loss of Ag load ? seen in early
  treatment phase
• Downgrading
• Loss of CMI gain in Ag load ? seen in the
  untreated patient
• All may be associated with sudden delayed
  hypersensitivity reaction i.e. type IV reaction
  leading to tissue damage

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Immunological complications lepra reactions

• Type II reaction Erythema Nodosum Leprosum (ENL)
  occurs towards the lepromatous pole
• Accumulation of dead M. lepra leads to deposits
  of Ags Abs in tissue
• This forms the Focus of Arthus reaction which
  consists of vasculitis ?erythematous nodule
  formation hence Erythema Nodosum Leprosum (ENL)
• Either type of reaction may cause acute or
  insidious damage to nerves
• In case of type I reaction damage to all or any
  infected tissue may occur

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Sites of Nerve damage

• Nerve damage is extensive in strong CMI
• Sites of predilection
• Ulnar nerve Proximal to olecranon groove
• Posterior tibial nerve Posterior to medial
  malleolus
• Common peroneal nerve Popliteal fossa around
  neck of fibula
• Radial cutaneous nerve Wrist

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Nerve damage

• Other nerves
• Facial nerve
• Great auricular nerve From C2 and C3
• Median nerve Proximal to flexor retinaculum
• Nerve damage leads to
• Anesthesia,
• Weakness,
• Contractures
• Autonomic dysfunction
• All these lead to Trauma, burns, tissue necrosis
  and finally ? disability mutilation

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Clinical features

• Early leprosy Indeterminate leprosy
• Commonest early lesion
• ? Area of numbness on the skin or a visible skin
  lesion
• Most common on the
• Face, extensor surface of the limbs, buttocks, or
  trunk
• Spared sites
• Scalp, groins, axillae and lumbar region

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Early leprosy Indeterminate leprosy

• Lesions consists of
• One or few slightly hypo-pigmented or
  erythematous macules
• Few cm in diameter
• Margins are poorly defined
• Hair growth and nerve function are unimpaired
• Diagnosis
• skin BX? perineurovascular infiltration
• scanty AFBs may be found after prolonged search

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Clinical features

• Incubation period highly variable 2 40 yrs
  generally 5 7 yrs
• Early leprosy Indeterminate leprosy
• Less common early presentation
• Weakness or anesthesia due to peripheral nerve
  lesion
• Blister, burn or ulcer in absence of skin lesion
  in anesthetic hand or foot

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Clinical features

• Rarely may present with features of lepra
  reaction
• Pain in a nerve
• Sudden palsy
• Multiple new skin lesions
• Pain in eye
• Systemic febrile illness
• Nasal stuffiness, discharge or epistaxis are
  common symptoms of early LL

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ESTABLISHED LEPROSY DETERMINATE LEPROSY

• After a variable period of time
• Determinate leprosy develops
• Typical lesions of polar leprosy

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Diagnosing leprosy History

• Three things are important (history, exam,
  invest)
• History (symptoms)
• Early leprosy
• Skin patches
• Small, recent, pale or redder than normal skin
• Numbness tingling
• Feet and hands
• Burning sensation
• In the skin
• Slight weakness
• Face, hands and feet

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Diagnosing leprosy History

• Late leprosy
• Skin patches More and larger
• Loss of sensation Painless
• Injuries
• Burns
• Ulcers on the feet hands
• Obvious nodules thickened skin
• (infiltrations)
• More severe weakness or paralysis
• Muscles of Face, Hands or Feet

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Diagnosing leprosy Examination

• Three cardinal signs of leprosy during
  examination
• Visible skin patch with
• Diminished or loss of sensation
• Light Touch, Sharp Pain
• Nerve enlargement
• Great Auricular Nerve,
• Ulnar N, Median N, Radial Cutaneous N,
• Peroneal N, Posterior Tibial Nerve
• AFB Demonstration
• In skin smear

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Diagnosing leprosy Investigations

• Investigations/ laboratory tests
• Skin smear for Z-N staining
• Neg in TT and indeterminate leprosy
• Skin biopsy
• Important in TT, BB, LL
• Nerve biopsy
• Only necessary if no skin lesions e.g. Pure
  neural TT or BB
• Lepromin reaction (mitsuda reaction)
• Neg in LL
• Usually Neg in BB
• Strongly Pos in TT
• Mod pos in Indeterminate L

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Diagnosing leprosy Other investigations

• Histamine test
• Apply a drop of 11000 Histamine HCL on the skin
• Scratch with needle
• Watch for normal triple reaction (Lewis
  reaction)
• Erythema
• Wheal
• Surrounding larger reflex erythema
• Axon reflex
• In leprosy only a wheal is formed
• Absence of axon flare indicates nerve damage

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Other investigations

• Sweat test
• Inject 0.1 ml of 1100 pilocarpine chlorohydrate
  i/c
• into affected area painted with starch iodine
  soln.
• Sweat in normal skin changes starch-iodine to
  blue
• Neg reaction in leprosy
• Biochemical investigations
• Cholesterol ?
• Total serum lipids ?
• Cryoglobulin ?
• Globulin?

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Characteristic lesions of polar leprosy

• TUBERCULOID LEPROMATOUS
• Lesions 1-10 100s/confluent
• Distrib assym symm
• Margins clear vague
• Anest slight, late
• Nerve enl slight
• Mucosa 0
• M bacilli

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The Bacterial Index (BI)

• The density of leprosy bacilli in
• Oil Immersion Fields (OIF)
• BI 1 1 10 bacilli in 100 OIF
• 2 1 10 bacilli in 10 OIF
• 3 1 10 bacilli in 1 OIF
• 4 10 100 bac in average OIF
• 5 100 1000 in average OIF
• 6 gt 1000 in average OIF

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The morphological Index (MI)

• Percentage of living bacilli out of total number
• in the smear given as percentage
• MI indicates whether bacilli are viable and
  capable of
• Reproduction (infective) or not
• Wholly stained bacilli (solid rods)
• Viable bacilli
• Capable of reproduction
• Absence of central staining or diffuse irregular
  polar staining
• Non- viable bacilli
• Not capable of reproduction

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Diagnosis of leprosy??

• Diagnose leprosy
• If one of the following cardinal signs is
  positive
• Skin lesion with loss of sensation
• One or more enlarged peripheral nerves
• Positive skin smear for AFB

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Classification of leprosy preparation for
treatment

• Important in order
• To decide on treatment regime
• Two main categories of leprosy to treat
• Paucibacillary leprosy
• Multibacillary leprosy
• Categorization is based on
• Number of leprosy skin lesions
• Presence of bacilli in skin smear

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Categorization for treatment

• Paucibacillary leprosy
• 1 5 leprosy skin lesions
• Negative skin smear
• Multibacillary leprosy
• 6 leprosy skin lesions
• Positive skin smear

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TREATMENT

• Leprosy
• Was treated differently in the past.
• The first breakthrough
• Occurred in the 1940s
• With the development of
• Diamino Diphenyl Sulfone (DDS dapsone)
• Today
• Leprosy is treated According to
• Respective NTLP regime
• Based on WHO recommendations

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Leprosy treatment

• Treatment according to Tanzanian NTLP
• Based on microbiological classification
• PB leprosy
• Rifampicin monthly for 6 months 600 mg
  (supervised)
• Dapsone daily for 6 months 100 mg (unsupervised)
  
• MB leprosy
• Rifampicin monthly for 12 months 600 mg
  (supervised)
• Clofazimine High dose monthly for 12 moths 300
  mg (supervised)
• Dapsone daily for 12 months 100 mg
  (unsupervised)
• Clofazimine Low dose daily for 12 months 50 mg
  (unsupervised)

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Lepra reactions

• Type 1 reaction (CMI dependent)
• Patients CMI to leprosy often changes thus pt
  moves to different parts of disease spectrum
• Upgrading or downgrading (Usualy upgrading)
• Occurs in pts with unstable leprosy
• Borderline tuberculoid (BT)
• True borderline leprosy (BB)
• Borderline lepromatous (BL)

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Lepra reactions

• Type II lepra reaction
• Erythema Nodosum Leprosum ENL
• A form of Arthurs reaction triggered by
• Circulating immune complexes
• Existing leprosy lesions are not affected
• Instead an EN like immune complex vasculitis
  occurs
• Sometimes EM like lesions occur
• Usually seen in LL leprosy

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Systemic involvement

• Eyes untreated LL
• Invariably leads to eye disorders painless
  periconneal conjunctiviitis conjunctivitisi
• Kidneys Affected in 75
• albuminuria,
• glomerulonephritis,
• NS
• Liver and spleen Affected in 1/3
• Gonads
• Painful bilateral epididymitis
• orchitis in LL

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Systemic involvement

• Eyes untreated LL
• Painless pericorneal conjunctivitis (invariably)
• Kidneys Affected in 75
• Albuminuria
• Glomerulonephritis
• Nephrotic syndrome
• Liver and spleen Affected in 1/3
• Gonads in LL
• Painful bilateral epididymitis
• Orchitis