A. Smržová. III. Interní klinika FN Olomouc nefrologická, revmatologická a endokrinologická

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1 A. Smržová III. Interní klinika FN Olomouc nefrologická, revmatologická a endokrinologická

2 Systemic vasculitis destructive inflamatory of the walls of blood vessels.

3 Pathologist Inflammatory destruction of blood vessels Infiltration of vessel wall with inflammatory cells Leukocytoclasis Elastic membrane disruption Fibrinoid necrosis of the vessel wall Ischemia, occlusion, thrombosis Aneurysm formation Rupture, hemorrhage Rheumatologist A clinicopathologic process characterized by inflammatory destruction of blood vessels that results in occlusion or destruction of the vessel and ischemia of the tissues supplied by that vessel. Systemic vasculitides

4 Normal Artery Artery: WBC inflammation in wall

5 How we can vasculitis clasified? 1)Primary x secondary vasculitides 2)Classification by vessel size 3)ANCA positivity/negativity

6 Chapel Hill clasification from 2012 (Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides) Jennette JC et al revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum Jan;65(1):1-11.

7 Jennette JC et al revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum Jan;65(1):1-11.

8 Jennette JC et al revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum Jan;65(1):1-11.

9 Large-vessel vasculitis Giant cell arteritis, Takayasu s arteritis Behcet s disease, Cogan s syndrome Medium-vessel vasculitis Polyarteritis nodosa Buerger s disease, Central nervous system vasculitis, Kawasaki s disease, Rheumatoid vasculitis Small-vessel vasculitis Wegener s, microscopic polyangiitis, Churg-Strauss Cryoglobulinemic vasculitis, Henoch-Schönlein purpura,

10 Large-vessel vasculitis Aorta and the great vessels (subclavian, carotid) Claudication, blindness, stroke Medium-vessel vasculitis Arteries with muscular wall Mononeuritis multiplex (wrist/foot drop), mesenteric ischemia, cutaneous ulcers Small-vessel vasculitis Capillaries, arterioles, venules Palpable purpura, glomerulonephritis, pulmonary hemorrhage

11 3 main groups of pathogenetic mechanisms behind vasculitis- 1. Immune complex formation 2. ANCA mediated 3. T lymphocyte mediated with Granuloma formation

12 Henoch Schonlein purpura- IgA mediated SLE & other collagen vascular diseases- ANA Serum sickness Polyarteritis Nodosa- Hepatitis B ag Essential Mixed Cryoglobinemia- Hepatitis C virion *deposition of immune complexes in the blood vessels activation of complements destruction of vessel wall (acute & chronic inflammation)

13 P-ANCA (anti-proteinase 3)- Wegener s C-ANCA (anti-mpo) - Churg Strauss vasculitis - Microscopic Polyangiitis - Wegener s granulomatosis * Aberrant expression of proteinase 3 and MPO over the surface of the neutrophils formation of antibodies destruction of neutrophils vessel wall damage

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15 Giant cell arteritis Takayasu s arteritis Wegener s granulomatosis Churg Strauss vasculitis *classical granuloma formation (giant cells and epitheloid cells in a backround of fibrinoid necrosis) can be demonstrated in the corresponding vessel biopsy

16 1. Unexplained signs and symptoms 2. Multisystem involvement 3. Unexplained elevated ESR/CRP 4. Skin lesions (palpable purpura) 5. Ischemic vascular changes (Raynaud s, gangrene, livedo, claudication) 6. Glomerulonephritis 7. Mononeuritis multiplex 8. Intestinal angina 9. Inflammatory ocular disease 10. Arthralgia's/arthritis, myalgia's 11. Sudden visual loss/headache

17 Temporal arteritis Elderly persons more than 50 yrs. of age Non specific symptoms, Headache, Elevated ESR BLINDNESS-most serious complication Jaw claudication, Scalp pain, Scalp Tenderness Polymyalgia Rheumatica- different end of the spectrum of Giant Cell Arteritis

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19 Pulseless Disease Middle aged females Aorta and its branches mainly involved Subclavian vessels, Carotid vessels, Mesentric vessels Chronic and Relapsing course

20 Renal arteries most commonly involved leading to renovascular hypertension Pulmonary vessels NEVER involved Association with patients of o Hepatitis B o Hairy cell leukemia

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23 Mucocutaneous Lymph node syndrome Children < 5 years of age mostly Desquamative erythematous rashes involving the skin, mucus membranes, cervical lymphadenopathy 25 % develop coronary artery aneurysms in the convalescent stage of the illness

24 Usually Pulmonary capillaritis PLUS Glomerulonephritis Granulomas +, Asthma + Churg Strauss Granulomas +, NO asthma Wegener s NO granulomas, NO asthma Microscopic Polyangiitis

25 Classical triad URT + LRT + renal Chronis sinusitis, Pulmonary nodules, Pulmonary cavities, Rapidly Progressive Glomerulonephritis Cutaneous vasculitis, Eye lesions may be present Non specific symptoms may predominate

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28 Saddle nose deformity Relapsing polychondritis May also occur in Wegener s granulomatosis and syphilis

29 Asthma, Eosinophilia with pulmonary infiltrates, glomerulonephritis Myocardial involvement most common cause of death Microscopic Polyangiitis Pulmonary alveolar capillariitis, glomerulonephritis

30 2nd decade Palpable purpura over lower limbs, Gastrointestinal complaints (abd.colicky pain, blood in stools), Fever, polyarthralgia Increased IgA levels in blood

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32 5 % of Chronic Hepatits C pts. Have EMC Cryoglobulins formed agianst HCV RNA Pulmonary, renal ( MPGN ), cutaneous vasculitis Thromb Angiitis Obliterans Chronic heavy Smokers Inflammation of arteries, veins, nerves Upper and lower limb gangrene, Instep claudication, rest pain

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34 SLE Sjörgren syndrom

35 Behcet s disease (Recurrent OculoOroGenital ulcerations with vasculitis) Idiopathic Cutaneous vasculitis Isolated Vasculitis of CNS Relapsing Polychondritis Polyangiitis overlap syndromes (features of more than 1 vasculitis)

36 Mild Anemia Anemia of Chronic Disease Differential Leucocyte Count: Predominant eosinophils- Churg Strauss ESR Non specific But useful test to suggest presence of underlying inflammatory process Higher by GCA

37 Urine routine- RBCs with active sediments suggest Glomerulonephritis (Renal involvement of small vessel vasculitis) Proteinuria Creatinine, dynamic by GPA in days Viral Markers - Hep. B Poly Arteritis Nodosa - Hep.C Essential Mixed Cryoglobulinemia

38 Acute Phase Reactants Highly sensitive C reactive Protein, Alpha 2 globulin Chest X ray / HRCT thorax: -Pulmonary infiltrates- small vessel vasculitis -Pulmonary cavities- Wegener s granulomatosis -Sinusitis of Wegener s -Granulomatosis of paranasal space, orbita -PET/CT - GCA

39 Immunoglogulin levels (IgG, M, A) - Usually hypergammaglobulinemia - Elevated IgA levels Henoch Sconlein Purpura Cryoglobulins- Essential Mixed Cryoglobulinemia Rheumatoid Factors -To detect secondary vasculitis Rheumatoid Arthrits -Significantly raised in Essential Mixed Cryoglobulinemia ANA -screening of SLE, collagen vascular disorders in suspicion of secondary vasculitis

40 Complement levels (reduced in immune compex mediated diseases)- EMC, HSP ANCA P-ANCA: Wegener s Granulomatosis C-ANCA: Microscopic polyangiitis, Churg Strauss, Wegener s vasculitis

41 Renal Biopsy- to detect glomerulonephritis especially in small vessel vasculitis RPGN- seen in pauci immune vasculitis MPGN- seen in EMC Skin Biopsy- to detect leukocytoclasis in cutaneous vasculitis all small vessel and secondary vasculitides

42 Temporal Artery Biopsy- Giant Cell Arteritis Pulmonary tissue Biopsy- Small vessel vascultides Upper Airway biopsies- Wegener s Vasculitis * Main purpose of biopsy is to study presence of leukocytoclasis, characterisitc pathological alterations in tissues, GRANULOMAS * Immunofluorescence also helps to study immune complex deposition, IgA deposition, Complement deposition

43 Helps specially in in arteries that cannot be biopsied easily like Aorta, Coronary artery, Mesentric vessels Presence of vascular patency, Aneurysms Aortic Angiography- Takayasu s Cerebral Angiography- Isolated CNS vascultis Renal Angiography- PAN Coronary Angiography- Kawasaki s Lower limb arteriography-buerger s Disease (TAO)

44 TREATMENT

45 Immuno Suppression Glucocorticoids- oral / IV methyl prednisolone Cyclophosphamide Methotrexate Azathioprine Cyclosporine Mycophenolate mofetile Rituximab- anti CD 20 ab AntiTNF therapies- Tocilizumab, Infliximab, Adalimumab, Etanacerpt, Certulizumab

46 Wherever possible secondary causes (infections, malignancies) should be sought and treated Anti viral therapy (HCV, HBV) ASPIRIN therapy Kawasaki s, Giant cell arteritis Intravenous Immunogloguloin Therapy- Prevents coronary aneurysms in Kawasaki s

47 High dose Steroids (60 mg/day) is the only drug that works Ischemia of n. opticus i.v. 0,5-1g 3x Slow taper over time usually 1-2 years. Some patients require low dose (<10 mg/day) chronically Methotrexate 10-25mg per w. to reduce GC

48 Remission induction: Cyclophosphamide 2mg/kg po qd x 3-6 months [or 15 mg/kg IV q 2 wk x3 then q 3 weeks x 6-12 months] Prednisone 1mg/kg po qd x 1 month, then taper Remission maintenance (minimum 2 years) Methotrexate mg po q week + folate Azathioprine 2mg/kg po qd Mycophenolate mofetil 1-2 g d. Refractery: Rituximab 1g

49 Infections Malignancies Thrombotic Microangiopathies Drugs Others

50 Bacterial endocarditis Gonococcal Infection Syphilis Rickettsial diseases Histoplasmosis Coccidiomycosis Whipple s Lyme s

51 Atrial Myxomas Carcinomatosis Lymphomas TTP HUS Thrombotic Microangiopathies

52 Cocaine Phenytoin Sulfa drugs Penicillins Hydralazine Allopurinol Propylthiouracil Thiazides

53 SLE Amyloidosis Sarcoidosis Migraine Atheroembolic Disease