SEMINAR

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• SEMINAR
• Dr. AAKANKSHA GODIYAL

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LEPROSY
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Definition

• A chronic granulomatous infection and its
  sequalae caused by Mycobacterium leprae affecting
  skin and nerves primarily
• More than 800,000 new cases detected worldwise
  annually

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History

• Ancient disease
• Writings from India describe similar illness as
  early as 6th century BC
• Imported to Europe by troops of
  Alexander.European epidemic peaked in 13th
  century
• French settlers took it to Canada and black
  slaves to America

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• ARMAUER HANSEN of Norway attributed it to
  M.leprae in 1873
• Effective chemotherapy began with sulfones in
  1943
• Rifampicin introduced in 1970
• Grown in mouse footpad in 1961 in nine banded
  armadillo in 1971
• Sequence of genome published in 2001

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EPIDEMIOLOGY

• Endemic in all continents except Antarctica
• 2/3rd of worlds leprosy burden in Indian
  subcontinent
• Incidence800,000 per year
• Not always a tropical disease was endemic in
  norway till 20th century
• IP2 to 5 yr for tuberculoid 8 to 12 yr for
  lepromatous cases

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• Loss of 1 million disability adjusted life years
• Majority of cases before 35 yr age with median
  age less for tuberculoid cases
• Excess of male cases regularly found
• Clustering of cases well recognised
• HLA association

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• HLA-DR2/DR3 occur at higher frequency in TT/BT
  patients
• HLA-DQ1 increase susceptibility to BL/LL leprosy
• In South India assoc. found between
  paucibacillary leprosy and 10p13 chromosome
• Main source of infection- nasal discharge from
  untreated LL patients
• Not excreted by skin

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AETIOLOGY

• Classified under order Actinomycetalis and family
  Mycobacteriacae
• Straight/slightly curved rods with parallel sides
  and round ends
• Gram ve, acid fast. Characteristically acid
  fastness lost with pyridine extraction
• Obligate intracellular parasite especially in
  macrophages
• Noncultivable.. Grows at 30-33 degree centigrade
• Doubling time 12-13 days

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• Genome of M.leprae(3.27 megabases) shorter than
  M.tuberculosis(4.41 megabases)
• ULTRASTRUCTURE
• Following components from inside out
• Cytoplasm
• Trilaminar plasma membrane

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• Cell wall is 20 nm thick electron dense.
  Consists of peptidoglycan covalently attached to
  arabinogalactan polymer modified by branched
  chain mycolic acid. Lipoarabinomannan is another
  important component
• Capsule is electron transparent due to copious
  amounts of lipid- phthiocerol dimycocerosate
  phenolic glycolipid

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• PGL-1 is species specific and immunogenic
• Entry into nerves mediated by binding of PGL1 to
  laminin 2 in basal lamina of Schwann cells

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PATHOLOGIC SPECTRUM OF LEPROSY

• Lepra bacilli is non toxic. Clinicopathologic
  manifestations are result of immunopathology
• RIDLEY JOPLING ciassification defines categories
  along a spectrum depending on clinical,histopathol
  ogical, immunological indices
• TT,BT,BB,BL,LL
• TT and polar LL patients are stable while others
  move in either direction according to host
  response treatment

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PATHOLOGY

• TUBERCULOID LEPROSYTuberculoid granulomas found
  which tend to collect in foci around
  neurovascular elements.
• Each focus cosists of epitheloid cells at centre
  with surrounding zone of lymphocytes. Langhans
  giant cells sometimes found
• Some of the foci invade papillary zone and even
  erode basal layer

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• Bacilli not seen
• Dermal nerves are either completely destroyed or
  swollen by epithelioid cell granuloma.
  Occasionally there may be caseation within a nerve

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BORDERLINE LEPROSY

• BT
• Epithelioid cell granuloma more diffuse with a
  free but narrow papillary zone. Giant cells tend
  to be of foreign body type.
• Dermal nerves are moderately swollen by cellular
  infiltration or schwann cell proliferation
• Bacilli absent from dermis but likely to be found
  witin dermal nerves

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• Granulomas follow neurovascular bundles, sweat
  glands or erector pili muscles

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BB

• Diffuse epithlioid cell granuloma with scanty
  lymphocytes and no giant cells
• Papillary zone is clear and dermal nerves show
  slight swelling with cellular infiltrate
• Bacilli present within dermal nerves dermis in
  modest numbers

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BL

• There is macrophage granuloma in which some cells
  show slight foamy changes. Lymphocytes present in
  dense clumps or widely distributed in parts of
  granuloma. Occasionally epithelioid cells seen
• Papillary zone is free
• Bacilli are plentiful-singly or in clumps

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• Dermal nerves contain some cellular infiltrate
  perineurium may have laminated appearance(onion
  skin perineurium)

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LEPROMATOUS LEPROSY

• Extensive cellular infiltrate that is separated
  from flattened epidermis by Grenz zone of normal
  collagen
• In early lesions macrophages have mixed
  population of solid and fragmented bacilli.Solid
  bacilli are packed like cigars. Bacilli may be
  seen in endothelial cells
• No epithelioid cells. Lymphocytes not prominent.
  Plasma cells may be seen

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• In time degenerated bacilli accumulate in
  macrophages so called virchow or lepra cells
  which have foamy cytoplasm. In chronic lesions
  bacilli are disposed in large basiophilic clumps
  called globi
• Dermal nerves are well preserved contain large
  no of bacilli. Slowly become fibrotic

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LUCIO LEPROSY

• Show similar histological features but with
  characteristic heavy bacillation of small blood
  vessels in skin causing obliterative angiitis and
  ischaemic epidermal necrosis

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Histoid leprosy

• Shows highest load of bacilli majority are
  solid staining arranged in clumps like sheaves of
  wheat. Macrophages show storiform pattern similar
  to fibrohistiocytoma

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Type 1 reaction

• Edema within around granuloma
• In upgrading reaction granulomas become more
  epithelioid langhans giant cells are larger.
  There may be erosion of granuloma into lower
  epidermis
• Fibrinoid necrosis within granulomas or in dermal
  nerves

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• Downgrading reaction necrosis less common.
  Density of bacilli increases
• Multibacillary patients who upgrade on therapy
  show old foamy macrophages mixed with new
  epithelioid cell granulomas

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Type2 reaction(ENL)

• Lesions are foci of acute inflammation on chronic
  multibacillary leprosy. Neutrophils may be scanty
  or abundant to form abscess. Foamy macrophages
  with fragmented bacilli abundant

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Lucio reaction

• Endothelial proliferation leading to luminal
  obliteration seen with thrombosis of medium sized
  vessels in dermis subcutis
• Dense aggregates of AFB in walls of normal
  appearing vessels vessels with proliferative
  changes

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Indeterminate leprosy

• Mild lymphocyte macrophage accumulation around
  neurovascular bundles, sweat glands erector
  pili muscles. No epithelioid cell granulomas.
  Schwann cell hyperplasia may be seen
• Diagnosis rests on finding 1/more AFB in sites of
  predilection- erector pili muscles, just beneath
  epidermis or around a vessel

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CLINICAL FEATURES

• Indeterminate Leprosy Lesions found on face,
  extensor surface of limbs or buttocks.
• Consist of one or more slightly hyperpigmented or
  erythematous machules with poorly defined
  margins.
• Hair growth and nerve functions are normal.
• Found usually in children whose immune status is
  yet to be determined. Smears are negative.
  Sometimes thickened nerve is palpable.

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POLAR TUBERCULOID

• Primary lesion is a plaque assuming an annular
  configuration. Both the borders are sharply
  marginated.
• Lesion is indurated, elevated, scaly, dry,
  hairless and hypopigmented.
• Nearby sensory nerve may or may not be enlarged
  but the lesion is anaesthetic anhidrotic.
• Usually solitary.

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• Spontaneous cure is known.
• Upper limit of 10 cm on lesion size.

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BORDERLINE TUBERCULOID

• Primary lesion are plaques and papules.
• Annular configuration is common with both borders
  sharply defined but incomplete annular lesions
  may be seen. Satellite lesions present.
• Little scaling, less erythema, less induration,
  size more than 10 cm.
• Multiple asymmetric lesions are a rule.
• Loss of sensation in skin lesion, nerve trunk
  enlargement and palsies seen.

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• Nerve trunk involvement asymmetric and not more
  than 2.
• Nerve abscesses are most often seen in males with
  BT disease.

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MID BORDERLINE

• Immunological midpoint
• Characteristic lesions are annular with sharply
  marginated interior and exterior margins or large
  plaques with islands of normal skin within the
  plaque giving a Swiss cheese appearance or a
  classic dimorphic lesion.
• Because of instability BB is shortlived and
  rarely seen.

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BORDERLINE LEPROMATOUS

• Highly variable in clinical expression
• In 1/3rd patients classic dimorphic lesion seen.
  Annular lesions with both borders sharply defined
  uncommon but when they occur lepromatous like
  papules nodules seen.
• Lesions may be hypoaesthetic/anaesthetic but not
  necessarily so.
• Nerve trunk palsies have highest prevalence in
  BL.

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• Untreated BL has a relentless progression. When
  disease is extensive acral distal symmetric
  anaesthesia may be present.
• Course altered by reactional states.

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LEPROMATOUS LEPROSY

• Poorly defined skin coloured nodules are the most
  characteristic symmetrically distributed.
• Diffuse dermal infiltration is always present,
  manifested by widening of nasal root and fusiform
  swelling of fingers.
• Skin over forehead thickened causing Leonine
  facies. Earlobes thickened.
• Ciliary or superciliary madarosis

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• Macules are small, numerous, erythematous, vague
  and shiny with no loss of sensation or hair
  growth. Papules may also be present
• Sometimes, all 3 lesions may be present
• Chronic edema of leg is usual
• Nerve trunk palsies less common than in BL. Acral
  distal symmetric(glove stocking) anaesthesia
  seen

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• Systemic associations
• Nose may collapse with septal perforation, voice
  may become hoarse, upper incisor teeth may loosen
  and fall off
• Shortening of fingers and toes due to repeated
  trauma
• Anaesthetic skin liable to blister and ulceration
• Eyes- superficial punctate keratitis, insidious
  iritis (beginning as iris pearls)

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• Damage to cranial nerve V VII- corneal
  insensitivity and lag ophthalmos predispose
  cornea to injuries
• Bone changes occur late- periostitis of bones of
  leg and forearms, atrophy of distal phalanges of
  hands atrophy of phalanges, metatarsal tarsal
  bones of feet
• In skull atrophy of anterior nasal spine and of
  maxillary alveolar process lead to facies leprosa

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• Kidney- renal damage important cause of morbidity
  mortality (renal amyloidosis,
  glomerulonephritis, etc)

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PREGNANCY LEPROSY

• 1. Worsening of leprosy status (third trimester
  of pregnancy)
• 2. Type I reaction (during first six months of
  lactation)
• 3. Type II reaction (in third trimester first
  six months of lactation)
• 50 suffer deterioration of nerve function

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LUCIO LEPROSY

• Diffuse non nodular type. Described by Lucio and
  Alvarado in Mexico.
• hands, wide spread sensory loss. Shiny thickened
  skin, body hair loss, puffy
• Eyes- shiny appearence
• Anaemia, edema, ulceration of both legs
• Nasal symptoms present
• No motor palsies and eyes not damaged.

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HISTOID HANSENS

• Term introduced by Wade
• Applied to firm erythematous round shiny
  glistering nodules which appear on skin of
  patients whose disease is relapsing either
  because they have stopped treatment or because M.
  leprae has become drug resistant
• Histoid nodules contain elongated spindle shaped
  histiocytes with bacilli within them

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TYPE I LEPRA REACTION

• Delayed (type IV) hypersensitivity reaction
• Antigens from breaking down of lepra bacilli
  react with T-lymphocytes
• Seen in borderline patients
• Increase in CMI associated with treatment known
  as reversal reaction whereas reduction in
  immunity called downgrading reaction

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• Upgrading most common during first six months of
  treatment
• LLs-gtBL-gtBB-gtBT-gtTTs
• Rapidly developing change in some/all skin
  lesions- become erythematous, shiny, warm and
  tender. Sometimes necrosis occurs leading to
  ulceration. Lesions desquamate as the subside

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• Systemic features less common
• Nerve involvement- swelling of one or more nerves
  with pain and tenderness
• Most serious complication is motor disturbance
  and nerves at risk are ulnar, lateral popliteal
  and facial
• Paralysis can recover with prompt treatment

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• Edema of hands, feet or face
• Tenderness of palms and soles

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TYPE II LEPRA REACTION

• Is an immune complex syndrome (type III)
  hypersensitivity reaction
• Occurs almost always LLp/LLs and occasionally in
  BL
• No change of leprosy lesions but crops of
  brightly red nodules seen which come and go
• Systemic disturbance usual
• Unusual for it to occur during first six months
  of treatment

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• ENL lesions tend to be bilaterally symmetrical.
  Often tender and blanch with light pressure.
  Evanescent lasting two-three days
• Commonly on face, arms and thighs. Leave bluish
  stain as they fade
• In severe reactions lesions may become vesicular
  and break down (erythema necroticans)
• Other features- neuritis, myositis, arthritis,
  rhinitis, acute iritis, dactylitis,
  epididymoorchitis and proteinuria

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• Factors precipitating ENL
• Physical/ mental stress
• Immunization
• Intercurrent infection/injury/surgery
• Pregnancy/parturition
• Ingestion of KI besides anti-leprosy drugs

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LUCIO PHENOMENON

• Confined to diffuse non-nodular LL leprosy
  chiefly encountered in Mexicans
• Unique feature- seen only in untreated patients
• Painful red patches appear on the skin
  especially extremities, become purpuric, ulcerate
  and finally develop an eschar which falls off to
  leave a superficial atrophic scar
• Face and trunk are spared. Patients afebrile

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• Steroids- show good effect
• Thalidomide of no value
• Good results with Dapsone
• Excellent results with Rifampicin

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DIFFERENTIAL DIAGNOSIS

• I. Neurological conditions
• PALPABLE N. THICKENING WITHOUT
  ANAESTHESIA/SIGNS OF N. DAMAGE
• 1. Excessive muscular development
• 2. Pachydermoperiostitis

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• PALPABLE N. THICKENING WITH REGIONAL
  ANAESTHESIA WITH/WITHOUT MUSCLE WASTING
• Primary amyloidosis of peripheral nerves
• Familial hypertrophic interstitial neuritis

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• REGIONAL ANAESTHESIA WITH/WITHOUT MUSCLE
  WASTING BUT WITH NERVE THICKENING
• Recurrent/chronic progressive polyneuritis
• Peroneal muscular atrophy (charcot-marie-tooth
  syndrome)

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• REGIONAL ANAESTHESIA WITH/WITHOUT MUSCLE
  WASTING BUT WITHOUT NERVE THICKENING
• Syringomyelia
• Tabes dorsalis
• Peripheral neuropathies
• Hereditary sensory radicular neuropathy
• Congenital indifference to pain

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• II. DERMATOLOGICAL CONDITIONS
• None of the conditions listed below have all
  the three features of sensory loss, nerve
  thickening and ve skin smear for AFB
• Flat and hypopigmented lesions
• Morphoea
• Onchocerciasis
• Pityriasis alba
• Tenia versicolor

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• 5. Post kala azar dermal leishmaniasis
• 6. Yaws
• 7. Vitiligo
• B. Raised and pigmented lesions
• Follicular mucinosis (alopecia mucinosa)
• Granuloma annulare
• Granuloma multiforme
• Gyrate erythemas
• Kaposis sarcoma
• Cutaneous leishmaniasis
• Lupus erythematosus

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• 8. Lupus vulgaris
• 9. Mycobacterium marinum infection
• 10. Mycosis fungoides
• 11. Neurofibromatosis
• 12. P.rosea
• 13. Tinea corporis
• c. Generalized thickening of skin
• Systemic sclerosis
• Myxoedema
• Pachydermoperiostosis

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CONCLUSION
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THANK YOU
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