Vasculitis

Classification of Vasculitis ƒ

Large-sized Vessels ƒ ƒ

Edward Dwyer, M.D. ƒ

Division of Rheumatology

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 (ANCA) Associated ƒ ƒ ƒ

Wegener’s Granulomatosis Microscopic Polyangiitis Churg-Strauss Syndrome

Classification of Vasculitis ƒ

VASCULITIS is a primary inflammatory disease process of the vasculature

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Small-sized Vessels(cont.) ƒ

Immune-Complex mediated: ƒ ƒ ƒ ƒ

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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

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

Classification of Vasculitis

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Sequelae of Vasculitis ƒ

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

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Necrosis of vessel walls resulting in aneursymal dilatation and/or thrombosis causing organ ischemia, infarction, or hemorrhage.

Epidemiology of Giant Cell Arteritis ƒ

Age: > 50 years-old

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Racial/Ethnic Background (annual Incidence) ƒ ƒ ƒ

20/100,000 Northern European 2/100,000 African Americans and Hispanics 70% 5-year survival

Polyarteritis Nodosa with Fibrinoid Necrosis

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Polyarteritis Nodosa

Clinical Manifestations ƒ

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Fatigue Weight loss Fever

Gastrointestinal ƒ ƒ

Abdominal pain Abdominal catastrophes ƒ

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Shock secondary to aneurysmal rupture and resultant hemorrhage Shock secondary to sepsis from intestinal ischemia or infarction

Clinical Manifestations ƒ

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Mononeuritis multiplex (e.g. wrist drop, foot drop)

Skin ƒ ƒ

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Hypertension Renal Insufficiency

Peripheral Nervous System ƒ

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Angiogram Splenic Artery

Kidney ƒ

Vasculitis

Angiogram of Superior Mesenteric Artery

Constitutional symptoms ƒ

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Angiogram of Superior Mesenteric Artery

Nodules or ulcers Purpura

Digital gangrene

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Vasculitis of Interlobar Artery of the Kidney

Renal Arteriogram

Dermal Vasculitis

Dermal Vasculitis

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

Vasculitis

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Mononeuritis Multiplex

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 ƒ

Nerve Biopsy

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

Interferon-α Lamivudine

Wegener’s Granulomatosis ƒNecrotizing vasculitis of arterioles, capillaries, and postcapillary venules ƒAssociated with anti-neutrophil cytoplasmic antibodies (ANCA)

Granuloma

Digital Gangrene 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

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Clinical Manifestations ƒ

Upper Respiratory Tract ƒ ƒ

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Lower Respiratory Tract ƒ ƒ

Kidney

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Peripheral Nervous System

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Skin

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Vasculature involved Upper respiratory tract arterioles and capillaries

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Lung arterioles and capillaries ƒ

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Pulmonary “capillaritis”

Glomerulonephritis(crescentic) Mononeuritis multiplex Purpura

ANCA associated ƒ

> 90% have elevated titers of antineutrophil cytoplasmic antibodies

Kidney ƒ

Glomerulonephritis (“pauci immune”) ƒ

No immune deposits

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Skin

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Peripheral Nervous system

Epidemiology of Wegener’s Granulomatosis

Vasculitis

Pulmonary nodules Alveolar hemorrhage(hemoptysis)

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Chronic Sinusitis Chronic Otitis

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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

Anti-Neutrophil Cytoplasmic Ab (ANCA)

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ANCA in Wegener’s Granulomatosis ƒ

Saddle Nose Deformity

Cytoplasmic reactivity (C-ANCA) ƒ

Antigenic target = Proteinase 3 ƒ

Serine proteinase of lysosomal granules of monocytes and azurophilic granules of neutrophils

ƒ Assay: Anti-proteinase 3 Ab titers (ELISA)

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%

Mortality of Wegener’s Granulomatosis

Vasculitis

Pulmonary Nodules

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Untreated: 10% survival at 2 years

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Treated: 80% survival at 10 years

Granulomatous Inflammation

Multinucleated Giant Cell

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Pulmonary Hemorrhage

Palpable Purpura

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

Pulmonary Arteriolar Vasculitis

Necrotizing Glomerulonephritis*

Palpable Purpura

Necrotizing Arteritis in a Small Epineural Artery

* “Pauci-immune” Glomerulonephritis Jennette J and Falk R. N Engl J Med 1997;337:1512-1523

Vasculitis

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Treatment Regimen

Vasculature involved

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

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Gastrointestinal tract

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Kidney

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Skin

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

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Immune-complex mediated small vessel vasculitis

Renal insufficiency infrequent

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Purpura

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Arthralgia/arthritis

Henoch Schonlein Purpura

Pathogenesis

Age: 5-7 years old (range: 5-15) ƒ

Children: 20/100,000 ƒ

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Vasculitis

Intussusception

Hematuria/proteinuria ƒ

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Dermal arterioles, capillaries, and postcapillary venules

Abdominal pain (“purpura” of the small bowel, i.e., submucosal hemorrhage) ƒ

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Glomerulonephritis(mesangial)

Clinical Manifestations

Henoch Schonlein Purpura ƒ

Submucosal arterioles/venules

50% preceded by upper respiratory tract infection

Adults: