SEMINAR Dr. AAKANKSHA GODIYAL
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.