Vasculitis

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Henoch-Schonlein purpura. ▫ Hypocomplementemic Urticarial Vasculitis. ▫ Vasculitis associated with SLE, Rhuematoid arthritis, or other autoimmune diseases.
Vasculitis Edward Dwyer, M.D. Division of Rheumatology

Vasculitis

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Vasculitis

VASCULITIS is a primary inflammatory disease process of the vasculature

Determinants of the Clinical Manifestations of Vasculitis:

Vasculitis

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Target organ involved

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Size of vessel involved

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Pathobiology of the inflammatory process of involved vasculature

Classicfication of Vasculitis ƒ

Large-sized Vessels ƒ ƒ

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Medium-sized Vessels ƒ ƒ

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Giant Cell Arteritis Takayasu’s Arteritis Polyarteritis Nodosa Kawasaki’s Disease

Small-sized Vessels ƒ

Anti-Neutrophil Cytoplasmic Ab Associated ƒ ƒ ƒ

Vasculitis

Wegener’s Granulomatosis Microscopic Polyangiitis Churg-Strauss Syndrome

Classification of Vasculitis ƒ

Small-sized Vessels(cont.) ƒ

Immune Complex mediated: ƒ ƒ ƒ ƒ

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Vasculitis

Cryoglobulinemia Henoch-Schonlein purpura Hypocomplementemic Urticarial Vasculitis Vasculitis associated with SLE, Rhuematoid arthritis, or other autoimmune diseases Serum-sickness or drug-induced vasculitis

Classification of Vasculitis

Vasculitis

Sequelae of Vasculitis

Vasculitis

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Stenosis and/or occlusion of involved vasculature resulting in organ ischemia or infarction

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Necrosis of vessel wall resulting in aneursymal dilatation/rupture or intravascular thrombosis causing organ ischemia or infarction

Diagnostic Approaches ƒ

Biopsy of involved organs

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Radiographic evaluation of involved vessels ƒ ƒ ƒ

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Vasculitis

Conventional Angiography CT Angiography MR Angiography

Serology (e.g., autoantibodies)

Giant Cell Arteritis (Temporal Arteritis)

Vasculitis

Epidemiology of Giant Cell Arteritis ƒ

Age: > 50 years-old

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Racial/Ethnic Background (annual Incidence) ƒ ƒ ƒ

Vasculitis

20/100,000 Northern European 2/100,000 African Americans and Hispanics <1/1,000,000 Asians

Vasculature involved Thoracic aorta and major branches: ƒ

Carotid artery extra-cranial branches ƒ ƒ ƒ ƒ

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Vasculitis

Temporal artery Occipital artery Ophthalmic artery Posterior ciliary artery

Subclavian/axillary artery

Vasculitis

Vasculitis

Muscular Artery

(adventitia)

(intima)

Vasculitis

Temporal Artery Biopsy

Vasculitis

Temporal Artery Biopsy

Vasculitis

Giant Cell

Vasculitis

Clinical Manifestations ƒ

Constitutional ƒ ƒ ƒ

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Headache ƒ ƒ

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66% of patients Most commonly temporal, but frontal or occipital pain also common

Jaw pain(claudication) ƒ

Vasculitis

Fatigue Weight loss Fever

50% of patients

Clinical Manifestations ƒ

Visual loss ƒ

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Arm claudication ƒ

Vasculitis

Acute onset partial or complete visual field loss in 15-20% of patients 15% of patients

Giant Cell Arteritis Pathogenesis

Weyand, C. M. et al. N Engl J Med 2003;349:160-169

Vasculitis

Temporal Arteritis Pathogenesis

Weyand, C. M. et al. N Engl J Med 2003;349:160-169

Vasculitis

Temporal Arteritis Pathogenesis

Weyand, C. M. et al. N Engl J Med 2003;349:160-169

Vasculitis

Temporal Arteritis Pathogenesis

Weyand, C. M. et al. N Engl J Med 2003;349:160-169

Vasculitis

Vasculitis

Thoracic Aortic Aneurysm

Vasculitis

Laboratory Abnormalities ƒ

Elevated Acute Phase Reactants ƒ ƒ ƒ

Vasculitis

Erythrocyte sedimentation rate (ESR) C-reactive protein Elevated IL-6 levels

Diagnosis ƒ ƒ

Vasculitis

Temporal Artery biopsy Elevation of acute phase reactants

Giant Cell Arteritis of Temporal Artery

Weyand C and Goronzy J. N Engl J Med 2003;349:160-169

Vasculitis

Treatment ƒ

Glucocorticoids ƒ

Vasculitis

Prednisone 1 mg/kg q d with tapering regimen over 4-6 months

Polyarteritis Nodosa ƒ

Necrotizing arteritis of mediumsized muscular arteries ƒ

Vasculitis

Pathology: “fibrinoid necrosis”

Vasculature involved ƒ ƒ ƒ ƒ

Vasculitis

Superior mesenteric artery Celiac and hepatic arteries Renal artery Muscular arteries of the extremities

Epidemiology of Polyarteritis Nodosa

Vasculitis

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Age: 20-70 years-old

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No racial or ethnic predilection

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Incidence ƒ

2-4/1,000,000 annual incidence

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70-80/1,000,000/ in regions which are endemic for Hepatitis B

Hepatitis B Virus Association

Vasculitis

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Usually occurs during the first 6 months after infection

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Usually positive for surface and e antigen

Necrotizing Arteritis

Vasculitis

Polyarteritis Nodosa

Vasculitis

Clinical Manifestations ƒ

Constitutional symptoms ƒ ƒ ƒ

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Gastrointestinal ƒ

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Abdominal pain

Kidney ƒ

Vasculitis

Fatigue Weight loss Fever

Hypertension

Clinical Manifestations ƒ

Peripheral Nervous system ƒ

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Skin ƒ

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Vasculitis

Mononeuritis multiplex (e.g. wrist drop, foot drop) Nodules or ulcers

Digital gangrene

Angiogram of Superior Mesenteric Artery

Vasculitis

Angiogram Splenic Artery

Vasculitis

Digital Gangrene

Vasculitis

Vasculitis

Mononeuritis Multiplex

Vasculitis

Sural Nerve Biopsy

Vasculitis

Renal Arteriogram--PAN

Vasculitis

Vasculitis

Vasculitis

Treatment ƒ

5 yr survival untreated: 13%

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Disease onset ƒ ƒ

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Duration of treatment ƒ

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At least one year

+HBV PAN ƒ

Vasculitis

Prednisone 1 mg/kg q d Oral cyclophosphamide 2 mg/kg q d

Interferon-α

Wegener’s Granulomatosis

Vasculitis

Granuloma ƒ

Vasculitis

Nodular aggregate of macrophages or cells derived from the monocyte-lineage, which is typically surrounded by a “rim” of lymphocytes, and commonly associated with the presence of multinucleated giant-cells

Vasculitis

Epidemiology of Wegener’s Granulomatosis

Vasculitis

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Age: 25-60 years-old

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No racial or ethnic predilection

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Prevalence: 5-7/100,000

Vasculature involved ƒ ƒ

Upper respiratory tract arterioles/capillaries Lung ƒ

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Kidney ƒ

Vasculitis

Arterioles and capillaries Glomerulonephritis (“pauci immune”)

Clinical Manifestations ƒ

Upper Respiratory Tract ƒ ƒ

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Lower Respiratory Tract ƒ ƒ

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Mononeuritis multiplex

Skin ƒ

Vasculitis

Glomerulonephritis

Peripheral Nervous System ƒ

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Pulmonary nodules Alveolar hemorrhage(hemoptysis)

Kidney ƒ

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Chronic Sinusitis Chronic Otitis

Purpura

Anti-Neutrophil Cytoplasmic Ab (ANCA)

Vasculitis

ANCA in Wegener’s Granulomatosis ƒ

Cytoplasmic reactivity (C-ANCA) ƒ Antigenic target = Proteinase 3 • Serine proteinase of lysosomal granules of monocytes and azurophilic granules of neutrophils

Vasculitis

Anti-Neutrophil Cytoplasmic Antibody ƒ

c-ANCA/anti-PR3 ELISA ƒ

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p-ANCA/anti-MPO ELISA ƒ ƒ

Vasculitis

Wegener’s Granulomatosis

Microscopic Polyangiitis Churg-Strauss Syndrome

Survival of Wegener’s Granulomatosis

Vasculitis

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Untreated: 10% at 2 years

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Treated: 80% at 8 years

Morbidity of Wegener’s Granulomatosis ƒ ƒ ƒ ƒ ƒ

Permanent renal insufficiency- 42% End-stage renal disease- 11% Hearing loss- 35% Nasal deformities- 28% Tracheal stenosis- 13%

Note: No significant morbidity from pulmonary disease

Vasculitis

Palpable Purpura

Vasculitis

Palpable Purpura

Vasculitis

Purpuric Dermal Vasculitis

Jennette J and Falk R. N Engl J Med 1997;337:1512-1523

Vasculitis

Pulmonary Nodules and Hemorrhage

Vasculitis

Alveolar Capillaritis in ANCA-associated Vasculitis

Jennette J and Falk R. N Engl J Med 1997;337:1512-1523

Vasculitis

Granulomatous Inflammation

Multinucleated Giant Cell

Vasculitis

Necrotizing Glomerulonephritis*

* “Pauci-immune” Glomerulonephritis

Vasculitis

Necrotizing Glomerulonephritis

Vasculitis

Treatment Regimen ƒ

Prednisone 0.5-1 mg/kg q d (tapered) plus cyclophosphamide 2 mg/kg q d for approximately one year ƒ ƒ ƒ

Vasculitis

85-90% response rate 75% complete remission 30-50% at least one relapse

Henoch Schonlein Purpura ƒ

Age: 5-7 years old (range: 5-15) ƒ

Children: 20/100,000 ƒ

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Vasculitis

50% preceded by upper respiratory tract infection

Adults: <1/100,000

Gender: male/female : 1.5/1

Vasculature involved ƒ

Gastrointestinal tract ƒ

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Kidney ƒ

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Glomerulonephritis

Skin ƒ

Vasculitis

Submucosal arterioles/venules

Dermal arterioles/venules

Clinical Manifestations ƒ

Abdominal pain ƒ

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Hematuria/proteinuria ƒ

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Vasculitis

Intussusception Renal insufficiency infrequent

Purpura Arthralgia/arthritis

Vasculitis

Glomerulonephritis in HSP

Vasculitis

Pathogenesis ƒ

Vasculitis

Tissue (vascular) deposition of IgAcontaining immune complexes

Immunoflourescence for IgA in Kidney

Vasculitis

Treatment ƒ

Prognosis: very favorable

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No indication for immunosuppression

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Supportive therapy: ƒ ƒ ƒ

Hydration Bed rest Analgesia ƒ

Vasculitis

Non-steroidal anti-inflammatory agents

Vasculitis Edward Dwyer, M.D. Division of Rheumatology

Vasculitis

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