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Vasculitis pathology
- 1. Objectives Define and classify vasculitis Describethe cause , pathogenesis , morphology and clinical presentation of various types of vasculitis
- 2. Vasculitis Vessel wall inflammation Pathogenesis • Immunemediated inflammation • Direct invasion of vessel wall by infectious pathology.
- 3. Non- infectious vasculitis Cause – Localor systemic immune response Immunologic Injury is caused by - • Immune complex deposition • Antineutrophil cytoplasmic antibodies • Antiendothelial antibody • Autoreactive T cells
- 4. Antineutrophil Cytoplasmic Antibodies (ANCAs) •Heterogeneous group of autoantibodies directed against o neutrophil primary granules, o monocyte lysosomes, and o endothelial cells. • ANCA associated vasculitis is “pauci-immune” as vascular lesions do not contain demonstrable antibody or complement. MCQ SAQ
- 5. – Classified accordingto antigen specificity/ intracellular distribution of target antigen – Anti-proteinase-3 (PR3-ANCA) / c -ANCA • Neutrophil azurophilic granule constituent. • trigerred by some infections • Eg. Wegener granulomatosis/ Polyangitis • Anti-myeloperoxidase (MPO-ANCA) / p-ANCA – MPO is a lysosomal granule involved in generating oxygen free radicals. – induced by therapeutic agents- propylthiouracil – Eg. Microscopic polyangiitis and Churg-Strauss syndrome ANCAs- MCQ’S ***
- 6. Antiendothelial antibodies Induced by defects inimmune regulation Eg. Kawasaki disease
- 9. GIANT-CELL (TEMPORAL) ARTERITIS •chronic, typically granulomatous inflammation of large to small- sized arteries. • Most common form of vasculitis • Elderly**, Rare before 50 years. • • Affects arteries in head (temporal arteries-thickened, nodular and tender) followed by vertebral and ophthalmic arteries.
- 10. GIANT-CELL (TEMPORAL) ARTERITIS.. C/F - vagueand constitutional— fever, fatigue, weight loss, facial pain or headache Giant-cell arteritis is a medical emergency - prompt recognition and treatment. Ophthalmic arterial involvement - permanent blindness
- 11. GIANT-CELL (TEMPORAL) ARTERITIS.. •Inflammatory lesions are segmental. (biopsy -2- to 3-cm length of artery) - nodular intimal thickening - reduced luminal diameter. • Classic lesions - medial granulomatous inflammation that leads to elastic lamina fragmentation. - Multinucleated giant cells (75%) Negative biopsy result does not exclude the diagnosis
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- 13. TAKAYASU ARTERITIS/ PULSELESSDISEASE • Granulomatous vasculitis of medium and larger arteries. • Clinical features: 1. Ocular disturbances 2. marked weakening of pulses in upper extremities. • Age : less than 50 years **
- 14. TAKAYASU ARTERITIS… • Classically involves •aortic arch • – pulmonary A. , coronary and renal arteries. • Transmural irregular • fibrous thickening of vessels with intimal hyperplasia • severe luminal • narrowing of major branch vessels
- 15. Takayasu aortitis… • Activedisease: destruction and fibrosis of arterial media associated with mononuclear infiltrates , granulomatous inflammation & giant cells • Chronic – Collagenous scarring with chronic inflammatory cells.
- 16. Polyarteritis nodosa (PAN) •Systemic vasculitis of medium or small-sized muscular arteries. • Typically involving renal and visceral vessels but sparing the pulmonary circulation. • ~ 30% of patients with PAN have chronic hepatitis B and HBsAg is positive – immune complex mediated etiology • Types- Classic idiopathic PAN , Cutaneous PAN, PAN associated with chronic hepatitis MCQ
- 17. Polyarteritis nodosa.. Typically Young adults. Clinicalfeatures - Malaise, fever, and weight loss • Hypertension due to renal involvement • Abdominal pain and malena • Diffuse muscular aches and pains • Peripheral neuritis Therapy - corticosteroids and cyclophosphamide
- 18. Polyarteritis nodosa.. • Morphology •segmental transmural necrotizing inflammation of small to medium-sized arteries • affect only part of vessel circumference. • Vessels of kidneys, heart, liver, and gastrointestinal tract
- 19. Polyarteritis nodosa.. • Acutephase - – transmural inflammation of arterial wall – mixed infiltrate of neutrophils, eosinophils, and mononuclear cells. – fibrinoid necrosis • Later phase - - fibrous thickening of vessel wall. • All stages of activity (early to late) coexist in different vessels or within same vessel- suggesting ongoing and recurrent insults. MCQ
- 20. KAWASAKI DISEASE/ Mucocutaneous lymph node syndrome Acute febrile,self-limited illness of infancy and childhood arteritis affecting large to medium- sized, and small vessels Predilection for coronary artery involvement - cause aneurysms - rupture or thrombose - acute myocardial infarctions
- 21. KAWASAKI DISEASE… Pathogenesis unknown infectious agents (viral)in triggering disease in genetically susceptible. Vascular damage is mediated by activated T cells and monocytes / macrophages
- 22. KAWASAKI DISEASE… • Morphology– – inflammation affecting entire thickness of vessel wall – fibrinoid necrosis is usually less prominent • C/F – – conjunctival and oral erythema and erosion – edema of hands and feet – erythema of palms and soles – a desquamative rash – cervical lymph node enlargement (Mucocutaneous lymph node syndrome)
- 23. Microscopic polyangiitis/ hypersensitivity /leukocytoclastic vasculitis Necrotizing vasculitis affecting capillaries, arterioles and venules. Necrotizing glomerulonephritis (90%) and pulmonary capillaritis are common. Skin, mucous membrane, lung, brain, heart, GIT, kidney , Muscle- involvement All lesions tend to be of same age are distributed widely MCQ
- 24. Microscopic polyangiitis- Pathogenesis Antibodyresponse to antigens – drugs (Penicillin), micro-organisms(streptococci), heterologous or tumour proteins. Immune complex deposition recruitment & activation of neutrophils within affected vascular beds Secondary immune response – MPO ANCA Clinical manifestations-
- 25. Microscopic polyangiitis- Morphology 1.Segmental fibrinoid necrosis of media 2. focal transmural necrotizing lesions 3. granulomatous inflammation is absent. • Spare medium and larger arteries- infarcts uncommon. • In postcapillary venules only infiltrating neutrophils, many undergoing apoptosis- leukocytoclastic vasculitis • Little or no immunoglobulin (“pauci-immune injury”).
- 26. Churg-Strauss Syndrome / Allergic granulomatosis and angitis •Small-vessel necrotizing vasculitis • Associated with asthma, allergic rhinitis, lung infiltrates, peripheral hypereosinophilia, and extravascular necrotizing granulomas. • Mechanism : hyper responsiveness to an allergic stimulus in patients with asthma • Trigger : leukotriene receptor antagonists
- 27. Churg- Strauss Syndrome… Vascular lesions- segmentaltransmural necrotizing inflammation , granulomas and eosinophils. MPO-ANCAs present (50%) Multisystem diseases with - • cutaneous involvement (palpable purpura), • gastrointestinal tract bleeding • renal disease (focal and segmental glomerulosclerosis) • Myocardial involvement- cardiomyopathy
- 28. Wegener Granulomatosis/ Granulomatosis withpolyangitis Necrotizing vasculitis characterized by – • Necrotizing granulomas of upper (ear, nose, sinuses, throat) or lower respiratory tract (lung) or both • Necrotizing or granulomatous vasculitis small to medium-sized vessels of most commonly lungs and upper airways • Focal necrotizing, crescentic glomerulonephritis MCQ
- 29. Wegener Granulomatosis- Pathogenesis PR3-ANCAs (up to95%)- marker of disease activity, prognosis and disease pathogenesis. T-cell–mediated hypersensitivity response
- 30. Wegener Granulomatosis- Morphology • Upperrespiratory tract lesions- Iinflammatory sinusitis with mucosal granulomas to ulcerative lesions of nose, palate, or pharynx, rimmed by granulomas with geographic patterns of central necrosis and vasculitis • Multiple granulomas coalesce to produce nodules in lung - cavitate • late stage - Granulomatous involvement of parenchyma and alveolar hemorrhage • Lesions may ultimately undergo progressive fibrosis and organization.
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- 32. Wegener Granulomatosis- Morphology •Renal Lesions – • Early : Glomeruli focal necrosism with isolated capillary loop thrombosis (Focal and segmental necrotising glomerulonephritis) • Advanced: Diffuse necrosis with excuberant parietal cell proliferation – cresent formation – (Cresentric glomerulonephritis)
- 33. Wegener Granulomatosis- Clinicalfeatures Males ~ 40 years Pneumonitis with bilateral nodular and cavitary infiltrates chronic sinusitis mucosal ulcerations of the nasopharynx evidence of renal disease
- 34. Behcet’s disease Small- to medium-vessel neutrophilic vasculitis presentsas a clinical triad of recurrent oral aphthous ulcers, genital ulcers, and uveitis
- 35. Thromboangiitis Obliterans (Buerger Disease) Segmental, thrombosing,acute and chronic inflammation of medium-sized and small arteries, tibial and radial arteries, With secondary extension into veins and nerves of extremities Leads to vascular insufficiency of extremities. exclusively in heavy cigarette smokers, usually before age 35
- 36. Vasculitis Associated withOther Noninfectious Disorders Vasculitis resembling hypersensitivity angiitis or classic polyarteritis nodosa Rheumatoid arthritis- Rheumatoid vasculitis systemic lupus erythematosus- Lupus vasculitis antiphospholipid antibody syndrome malignancy Systemic illnesses- mixed cryoglobulinemia, and Henoch-Schönlein purpura.
- 37. Infectious vasculitis Direct invasion of infectiousagents- Pseudomonas or fungi Aspergillus and Mucor species. Mycotic aneurysms- induce thrombosis and infarction.