Transcript LEPROSY - Medico

SEMINAR
Dr. AAKANKSHA GODIYAL
LEPROSY
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
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
 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
EPIDEMIOLOGY
 Endemic
in all continents except
Antarctica
 2/3rd of world’s leprosy burden in
Indian subcontinent
 Incidence:800,000 per year
 Not always a tropical disease; was
endemic in norway till 20th century
 IP=2 to 5 yr for tuberculoid & 8 to 12
yr for lepromatous cases
 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
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

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

 Genome
of M.leprae(3.27
megabases) shorter than
M.tuberculosis(4.41 megabases)
 ULTRASTRUCTURE
 Following components from inside
out:
 Cytoplasm
 Trilaminar plasma membrane


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
 PGL-1
is species specific and
immunogenic
 Entry into nerves mediated by
binding of PGL1 to laminin 2 in basal
lamina of Schwann cells
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,histopathological, 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

PATHOLOGY
TUBERCULOID LEPROSY:Tuberculoid
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

 Bacilli
not seen
 Dermal nerves are either completely
destroyed or swollen by epithelioid
cell granuloma. Occasionally there
may be caseation within a nerve
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

 Granulomas
follow neurovascular
bundles, sweat glands or erector pili
muscles
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
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
 Dermal
nerves contain some cellular
infiltrate & perineurium may have
laminated appearance(onion skin
perineurium)
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

 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
LUCIO LEPROSY
 Show
similar histological features but
with characteristic heavy bacillation
of small blood vessels in skin causing
obliterative angiitis and ischaemic
epidermal necrosis
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
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
 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
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
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
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

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.

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.
 Spontaneous
cure is known.
 Upper limit of 10 cm on lesion size.
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.

 Nerve
trunk involvement asymmetric
and not more than 2.
 Nerve abscesses are most often seen
in males with BT disease.
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.

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.

 Untreated
BL has a relentless
progression. When disease is
extensive acral distal symmetric
anaesthesia may be present.
 Course altered by reactional states.
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 +

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

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)

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

 Kidney-
renal damage important
cause of morbidity & mortality (renal
amyloidosis, glomerulonephritis, etc)
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
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.

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

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
 Upgrading
most common during first
six months of treatment
 LLs->BL->BB->BT->TTs
 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
 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
 Edema
of hands, feet or face
 Tenderness of palms and soles
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

ENL lesions tend to be bilaterally
symmetrical. Often tender and blanch with
light pressure. Evanescent lasting twothree 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

 Factors
precipitating ENL
 Physical/ mental stress
 Immunization
 Intercurrent infection/injury/surgery
 Pregnancy/parturition
 Ingestion of KI besides anti-leprosy
drugs
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

 Steroids-
show good effect
 Thalidomide of no value
 Good results with Dapsone
 Excellent results with Rifampicin
DIFFERENTIAL DIAGNOSIS
 I.
Neurological conditions
PALPABLE N. THICKENING WITHOUT
ANAESTHESIA/SIGNS OF N. DAMAGE
1. Excessive muscular development
2. Pachydermoperiostitis
PALPABLE N. THICKENING WITH
REGIONAL ANAESTHESIA
WITH/WITHOUT MUSCLE WASTING
1. Primary amyloidosis of peripheral
nerves
2. Familial hypertrophic interstitial
neuritis
REGIONAL ANAESTHESIA
WITH/WITHOUT MUSCLE WASTING
BUT WITH NERVE THICKENING
1. Recurrent/chronic progressive
polyneuritis
2. Peroneal muscular atrophy
(charcot-marie-tooth syndrome)
1.
2.
3.
4.
5.
REGIONAL ANAESTHESIA
WITH/WITHOUT MUSCLE WASTING
BUT WITHOUT NERVE THICKENING
Syringomyelia
Tabes dorsalis
Peripheral neuropathies
Hereditary sensory radicular
neuropathy
Congenital indifference to pain

A.
1.
2.
3.
4.
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
5.
6.
7.
B.
1.
2.
3.
4.
5.
6.
7.
Post kala azar dermal leishmaniasis
Yaws
Vitiligo
Raised and pigmented lesions
Follicular mucinosis (alopecia mucinosa)
Granuloma annulare
Granuloma multiforme
Gyrate erythemas
Kaposi’s sarcoma
Cutaneous leishmaniasis
Lupus erythematosus
8. Lupus vulgaris
9. Mycobacterium marinum infection
10. Mycosis fungoides
11. Neurofibromatosis
12. P.rosea
13. Tinea corporis
c. Generalized thickening of skin
1. Systemic sclerosis
2. Myxoedema
3. Pachydermoperiostosis
CONCLUSION