1 / 66

PRIMARY VASCULITIDES

PRIMARY VASCULITIDES. Amy Shultz, M.D. VASCULITIS DEFINITION. Presence of WBCs in vessel wall with reactive damage of mural structures Leads to bleeding, tissue ischemia/necrosis Primary—idiopathic Secondary—to another underlying disease (SLE, RA, cryglobulinemia). HISTORY.

nansen
Download Presentation

PRIMARY VASCULITIDES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. PRIMARY VASCULITIDES Amy Shultz, M.D.

  2. VASCULITIS DEFINITION • Presence of WBCs in vessel wall with reactive damage of mural structures • Leads to bleeding, tissue ischemia/necrosis • Primary—idiopathic • Secondary—to another underlying disease (SLE, RA, cryglobulinemia)

  3. HISTORY • 1866: Kussmaul & Maier—described nodular inflammation of muscular arteries • Termed periarteritis nodosa—later changed to polyarteritis nodosa (PAN)

  4. PATHOGENESIS • Remains largely unknown • Hypothesis: (Most likely multifactorial) -Immune complex deposition/humoral responses - Pathogenic T cell responses and granuloma formation - Autoantibodies - Cytokine activation - Infectious trigger—bacteria, mycobacteria, viruses - Drugs - Genetic predisposition

  5. VASCULITIDES • Fairly rare diseases • Presentation: highly variable making delays in diagnosis common • High morbidity and mortality • Therapeutic challenge often requiring prolonged & intensive immunosuppression.

  6. CLASSIFICATION • Individual diseases affect blood vessels of a particular size—clinical manifestations and wide range of disease severity. • Large Vessel Vasculitis: • Takayasu arteritis • Giant cell arteritis

  7. CLASSIFICATION • Medium vessel vasculitis: • Polyarteritis nodosa • Kawasaki disease (children) • Small vessel vasculitis: • Churg-Strauss syndrome • Wegener’s granulomatosis • Microscopic polyangiitis

  8. TAKAYASU ARTERITIS (TA) Chronic granulomatous vasculitis that affects the aorta, its main branches, and pulmonary arteries Women affected in 80-90% of cases Age of onset: 10-40 years Worldwide distribution, but greatest prevalence in Asians. U.S. incidence rate: 2.6/million

  9. TA (CLINICAL MANIFESTATIONS) • Systemic symptoms:Early phase • Fatigue • Malaise • Weight loss • Night sweats • Fever-low grade • Arthralgias~ 55% • Myalgias

  10. TA (CLINICAL MANIFESTATIONS) • Vascular compromise: Late phase • Aneurysm formation and rupture • Vessel stenosis/occlusion--ischemia • Catastrophic complications: • Aortic dissection/rupture • Aortic valve regurgitation • CVA • Hypertensive crisis • MI

  11. Subclavian Common carotid Renal Aortic arch/root Vertebral Pulmonary Coronary Arm claudication Visual changes, syncope, TIA, CVA, headaches HTN, renal failure AI, CHF Visual changes, dizziness Dyspnea, hemoptysis Chest pain, MI ARTERY MANIFESTATION

  12. TA (HISTOPATHOLOGY) • Cell-mediated mechanisms: • Infiltrating cells mainly consist of killer cells and gamma delta T lymphocytes • All layers of large arteries affected: • Inflammation • Granuloma formation • Giant cells

  13. TA (PHYSICAL EXAMINATION) • Asymmetric blood pressure measurements • Diminished pulses/pulseless • Bruits-subclavian, carotid, brachial, abd • HTN- RAS or decreased elasticity of aorta • Decreased hair growth, cool extremities, muscle wasting, gangrenous digits

  14. TA(LAB ABNORMALITIES) • Nonspecific: • Elevated ESR • Elevated CRP • Normochromic, normocytic anemia • Hypoalbuminemia • Autoantibodies: • Antiendothelial cell (recent studies value?) • ANA, ANCA, anti-DNA, APL: negative

  15. TA (IMAGING) Angiography usually necessary to confirm diagnosis and see extent of disease: Advantage: Provides clear outline of involved arteries & luminal patency Disadvantage: Does not show arterial thickening, invasive, & large dye load Helical CT angiography and MRA Becoming more popular Used to access continued disease activity Shows thickness and edema within wall

  16. TA (CLASSIFICATION CRITERIA) • Age of onset <40 • Claudication of extremities • Decreased pulsation in 1 or both brachials • >10mmHg SBP difference between arms • Bruit over 1 or both subclavian or abd. Aorta • Angiographic narrowing of aorta or branches • Patients must meet at least 3 of the 6 criteria

  17. TA (TREATMENT) • Corticosteroids: 60mg/day gradually tapered • Cytotoxic drugs: Chronic active disease (50%) • Methotrexate—17.5-25mg/week • Azathioprine—2mg/kg/day • Anti-TNF agents: clinical trials ongoing • Revascularization: bypass grafts vs. PTCA

  18. GIANT CELL ARTERITIS (GCA) • Granulomatous vasculitis affecting extra-cranial branches of arteries from the aortic arch • Most common systemic vasculitis: prevalence 200 per 100,000 • Occurs almost exclusively over 50 yrs of age • Female:male ratio 2:1

  19. PATHOGENESIS • Cell-mediated immune response against antigens in arterial wall. • Granulomatous inflammation • T cells secreting IL-2 & interferon γ • Humoral response against antigens in the arterial wall. • Immunoglobulin and complement deposits.

  20. CLINICAL MANIFESTATIONS • In most cases insidious onset of symptoms: • Fatigue • Fever • Weight loss • anorexia • Headache most common symptom: lacinating localized to regions along arteries in the scalp.

  21. Headache Weight loss/anorexia Jaw claudication Fever Malaise/fatigue PMR Transient visual symptom Synovitis Fixed visual symptom 68% 50% 45% 42% 40% 39% 16% 15% 14% GCA (CLINICAL MANIFESTATIONS)

  22. GCA (PE AND LAB) • Physical exam: Nodularity, tenderness, absent pulsations, bruits of involved arteries • Fundoscopic examination in patients with visual loss: pale, swollen disc with blurred margins • Lab: Markedly elevated ESR

  23. GCA (DIAGNOSIS) • Clinical Suspicion: Elderly patient with headache, visual symptoms, and high ESR • Diagnosis confirmed by temporal artery biopsy: • Shows panmural mononuclear cell infiltration with granulomas and giant cells • Treatment should be instituted promptly while biopsy is arranged

  24. GCA (TREATMENT) • Prednisone 40 to 60mg/day: initial dose • In patients with acute visual loss: Solu-medrol 1g/day x 3 days • Steroids can be tapered after clinical remission achieved: ESR and CRP normalized • Most patients off steroids by 2 years. Relapse rate 26-90% (highly variable). • Methotrexate studied in 2 RCT: conflicting results in ability to decrease relapse & steroid usage

  25. GCA( Follow-up) • Thoracic aortic aneurysms: Late manifestation • GCA patients 17 times more likely than age and sex matched people to develop these • Yearly chest x-rays are recommended for up to 10 years to identify patients with aneurysms prior to rupture.

  26. POLYARTERITIS NODOSA (PAN) • Systemic panmural necrotizing vasculitis typically affecting small and medium-sized arteries—fibrinoid necrosis • Most cases are idiopathic • 7 to 22% of cases associated with hepatitis B infection: must be r/o in all patients • Smaller percentage found in hairy cell leukemia, hepatitis C, and HIV • Classical PAN: ANCA negative

  27. PAN EPIDEMIOLOGY • Incidence: 0.7/100,000 • Male:female ~ 2:1 • Seen in all ages--peak 40-60 years of age • May range in severity from mild limited to 1 organ system to fulminate multisystem involvement.

  28. PAN (CLINICAL MANIFESTATIONS) • Systemic symptoms: fatigue, weakness, fever, arthalgias, myalgias (60-70%) • PNS: Mononeuritis multiplex—motor & sensory deficits (50-70%) • Skin:livedo reticularis, digital necrosis, skin ulcers, bullous eruptions, nodules, palpable purpura (45-60%) • Renal: Extra-glomerular vasculopathy mostly some GN—renal insufficiency, hypertension, and renal infarction (40-70%)

  29. PAN(CLINICAL MANIFESTATIONS) • GI:(30-50%)Mesenteric arteritisischemia • Stomach • Intestines • Liver • Gallbladder • Orchitis: rare seen more with HBV • Lab: non-specific (95%) • ↑ESR Normochromic/normocytic anemia • Thrombocytosis ↓albumin

  30. PAN(DIAGNOSIS) • Visceral/renal angiography: microaneurysms, ectasia, stenoses in medium-sized vessels • Biopsy: peripheral nerve or skin—focal segmental necrotizing vasculitis with mixed cell infiltrate and no granulomata affecting medium-sized arteries.

  31. PAN(PROGNOSIS) • Untreated: 13% 5 year survival rate • Main causes of death: renal failure, mesenteric, cardiac, cerebral infarction • Five-factor score: French vasculitis group • Proteinuria >1g/day • GI bleeding, perforation, infarct, pancreatitis • Renal insufficiency • Cardiomyopathy • CNS involvement

  32. PAN(TREATMENT) Prednisone 1mg/kg/day Cyclophosphamide 2mg/kg + steroids Azathioprine 2mg/kg + steroids Optimal duration of therapy is unknown. Relapse rate~40% If Hep B present, must treat.

  33. ANCA-ASSOCIATED VASCULITIS • Antineutrophilic cytoplasmic antibodies: • C-ANCA (cytoplamic pattern) antigen—proteinase-3 • P-ANCA (perinuclear pattern) antigen—myeloperoxidase Binding of C-ANCA & P-ANCA to their antigen targets in neutrophils →degranulation, respiratory burst, NO production, chemotaxis→contributes to vascular damage.

  34. CHURG-STRAUSS SYNDROME • Allergic granulomatosis & angiitis characterized by: • Allergic rhinitis • Asthma • Peripheral blood eosinophilia • Systemic vasculitis • Slight male predominance • Mean age at diagnosis: 40 years

  35. CHURG-STRAUSS(CLINICAL FEATURES) • Prodromal phase: 2nd to 3rd decades of life—atopic disease, allergic rhinitis, asthma • Eosinophilic phase: Peripheral blood eosinophilia and infiltration of multiple organs especially lungs and GI tract • Vasculitic phase: 3rd to 4th decades of life—systemic vasculitis

  36. CHURG-STRAUSS(CLINICAL FEATURES) • Asthma—98-100% • Mononeuritis multiplex—50-80% • Skin: palpable purpura, rash, tender subcutaneous nodules (50-80%) • Sinusitis—20-70% • CV—pericarditis, CHF, MI (35-50%) • GI—eosinophilic gastritis:pain, bleeding, colitis (30-60%)

  37. CHURG-STRAUSS(CLINICAL FEATURES) • Renal—focal segmental GN (10-50%) less common than in WG or MPA • Pulmonary infiltrates-40-75% • Transient patchy infiltrates • Pulmonary hemorrhage • Bilateral, nodular disease without cavitation • Pleural effusions: exudative & rich in eosinophils

  38. CHURG-STRAUSS(LAB ABNORMALITIES) • Peripheral eosinophilia >10% • Elevated IgE levels • P-ANCA/anti-MPO—70% • Elevated ESR • Normochromic/normocytic anemia • BAL—high percentage of eosinophils

  39. CHURG-STRAUSS (DIAGNOSIS) • Confirmed by surgical lung biopsy or biopsy of other affected tissues: • Eosinophilic infiltrates • Extensive areas of fibrinoid necrosis • Giant cell vasculitis of small arteries and veins • Necrotizing granulomas

More Related