VasculitisEdward Dwyer, M.D.Division of Rheumatology VasculitisVASCULITIS is a primary inflammatorydisease process of the vasculature1

Determinants of the Clinical Manifestations of Vasculitis: Target organ involved Size of vessel involved Pathobiology of the inflammatory processof involved vasculatureClassification of Vasculitis Large-sized Vessels Medium-sized Vessels Giant Cell ArteritisTakayasu’s ArteritisPolyarteritis NodosaKawasaki’s DiseaseSmall-sized Vessels Anti-Neutrophil Cytoplasmic Ab (ANCA) Associated VasculitisWegener’s GranulomatosisMicroscopic PolyangiitisChurg-Strauss Syndrome2

Classification of Vasculitis Small-sized Vessels(cont.) Immune-Complex mediated: Henoch-Schonlein purpuraCryoglobulinemiaHypocomplementemic Urticarial VasculitisVasculitis associated with SLE, Rhuematoidarthritis, or other autoimmune diseasesSerum-sickness or drug-induced vasculitisClassification of VasculitisVasculitis3

Sequelae of Vasculitis Stenosis and/or occlusion of involvedvasculature resulting in organ ischemiaor infarction Necrosis of vessel walls resulting inaneursymal dilatation and/or thrombosiscausing organ ischemia, infarction, orhemorrhage.Diagnostic Approaches Biopsy of involved organs Radiographic evaluation of involved vessels VasculitisConventional AngiographyCT AngiographyMR AngiographySerology (e.g., autoantibodies)4

Giant Cell Arteritis(Temporal Arteritis)Non-necrotizing vasculitis resulting intimalproliferation causing luminal stenosis orocclusionEpidemiology of Giant Cell Arteritis Age: 50 years-old Racial/Ethnic Background (annual Incidence) Vasculitis20/100,000 Northern European2/100,000 African Americans and Hispanics 1/1,000,000 Asians5

Vasculature involvedThoracic aorta and major branches: Carotid artery extra-cranial branches VasculitisTemporal arteryOccipital arteryOphthalmic arteryPosterior ciliary arterySubclavian/axillary artery6

Muscular ArteryadventitiamediaintimaTemporal Artery BiopsyVasculitis7

Temporal Artery BiopsyGiant CellVasculitis8

Clinical Manifestations Constitutional Headache FatigueWeight lossFever66% of patientsMost commonly temporal, but frontal or occipitalpain also commonJaw pain(claudication) 30% of patientsClinical Manifestations Visual loss Arm claudication VasculitisAcute onset partial or complete visualfield loss in 15% of patients5% of patients9

Laboratory Abnormalities Elevated Acute Phase Reactants Erythrocyte sedimentation rate (ESR)C-reactive proteinElevated IL-6 levelsGiant Cell Arteritis PathogenesisWeyand, C. M. et al. N Engl J Med 2003;349:160-169Vasculitis10

Giant Cell Arteritis PathogenesisWeyand, C. M. et al. N Engl J Med 2003;349:160-169Giant Cell Arteritis PathogenesisWeyand, C. M. et al. N Engl J Med 2003;349:160-169Vasculitis11

Giant Cell Arteritis PathogenesisWeyand, C. M. et al. N Engl J Med 2003;349:160-169Vasculitis12

Optic Nerve IschemiaThoracic Aortic AneurysmVasculitis13

Thoracic Aortic AneurysmDiagnosis Elevated Acute Phase Reactants VasculitisErythrocyte sedimentation rate(ESR)C-reactive proteinTemporal Artery biopsy14

Giant Cell Arteritis of Temporal ArteryWeyand C and Goronzy J. N Engl J Med 2003;349:160-169Treatment Glucocorticoids VasculitisPrednisone 1 mg/kg q d withtapering regimen over 4-6 months15

Polyarteritis Nodosa Necrotizing arteritis of mediumsized muscular arteries Pathology: “fibrinoid necrosis”Vasculature involved VasculitisSuperior mesenteric arteryCeliac and hepatic arteriesRenal arteryMuscular arteries of the extremities16

Epidemiology of Polyarteritis Nodosa Age: 20-70 years-old No racial or ethnic predilection Incidence 2-4/1,000,000 annual incidence 70-80/1,000,000/ in regions whichare endemic for Hepatitis BHepatitis B Virus AssociationVasculitis Usually occurs during the first 6months after infection Usually positive for HBAgs and eantigen17

Prognosis of Polyarteritis Nodosa Untreated: 13% 5-year survival Treated: 70% 5-year survivalPolyarteritis Nodosa with Fibrinoid NecrosisVasculitis18

Polyarteritis NodosaClinical Manifestations Constitutional symptoms FatigueWeight lossFeverGastrointestinal Abdominal painAbdominal catastrophes VasculitisShock secondary to aneurysmal rupture andresultant hemorrhageShock secondary to sepsis from intestinal ischemiaor infarction19

Clinical Manifestations Kidney Peripheral Nervous System Mononeuritis multiplex (e.g. wrist drop,foot drop)Skin HypertensionRenal InsufficiencyNodules or ulcersPurpuraDigital gangreneAngiogram of Superior Mesenteric ArteryVasculitis20

Angiogram of Superior Mesenteric ArteryAngiogram Splenic ArteryVasculitis21

Vasculitis of Interlobar Artery of the KidneyRenal ArteriogramVasculitis22


Dermal VasculitisDermal VasculitisJennette J and Falk R. N Engl J Med 1997;337:1512-1523Vasculitis24

Mononeuritis MultiplexNerve BiopsyVasculitis25

Digital GangreneTreatment 5 yr survival untreated: 13% Disease onset Duration of treatment At least one year HBV PAN VasculitisPrednisone 1 mg/kg q dOral cyclophosphamide 2 mg/kg q dInterferon-αLamivudine26

Wegener’s Granulomatosis Necrotizing vasculitis of arterioles,capillaries, and postcapillary venules Associated with anti-neutrophilcytoplasmic antibodies (ANCA)Granuloma VasculitisNodular aggregate of macrophages or cellsderived from the monocyte-lineage, which istypically surrounded by a “rim” of lymphocytes,and commonly associated with the presence ofmultinucleated giant-cells27

Vasculature involved Upper respiratory tract arterioles and capillaries Lung arterioles and capillaries Pulmonary “capillaritis”Kidney Glomerulonephritis (“pauci immune”) VasculitisNo immune deposits Skin Peripheral Nervous system28

Epidemiology of Wegener’s Granulomatosis Age: 25-60 years-old No racial or ethnic predilection Prevalence: 5-7/100,000Clinical Manifestations Upper Respiratory Tract Lower Respiratory Tract Mononeuritis multiplexSkin VasculitisGlomerulonephritis(crescentic)Peripheral Nervous System Pulmonary nodulesAlveolar hemorrhage(hemoptysis)Kidney Chronic SinusitisChronic OtitisPurpura29

ANCA associated 90% have elevated titers of antineutrophil cytoplasmic antibodiesAnti-Neutrophil Cytoplasmic Ab (ANCA)Vasculitis30

ANCA in Wegener’s Granulomatosis Cytoplasmic reactivity (C-ANCA) Antigenic target Proteinase 3 Serine proteinase of lysosomal granulesof monocytes and azurophilic granules ofneutrophils Assay: Anti-proteinase 3 Ab titers (ELISA)Morbidity of Wegener’s Granulomatosis VasculitisPermanent renal insufficiency- 42%End-stage renal disease- 11%Hearing loss- 35%Nasal deformities- 28%Tracheal stenosis- 13%31

Mortality of Wegener’s Granulomatosis Untreated: 10% survival at 2 years Treated: 80% survival at 10 yearsSaddle Nose DeformityVasculitis32

Pulmonary NodulesGranulomatous InflammationMultinucleated Giant CellVasculitis33

Pulmonary HemorrhageJennette J and Falk R. N Engl J Med 1997;337:1512-1523Pulmonary Arteriolar VasculitisVasculitis34

Necrotizing Glomerulonephritis** “Pauci-immune” GlomerulonephritisPalpable PurpuraVasculitis35

Palpable PurpuraNecrotizing Arteritis in a Small Epineural ArteryJennette J and Falk R. N Engl J Med 1997;337:1512-1523Vasculitis36

Treatment Regimen Prednisone 0.5-1 mg/kg q d (tapered) pluscyclophosphamide 2 mg/kg q d for approximatelyone year 85-90% response rate75% complete remission30-50% at least one relapseHenoch Schonlein Purpura VasculitisImmune-complex mediated smallvessel vasculitis37

Henoch Schonlein Purpura Age: 5-7 years old (range: 5-15) Children: 20/100,000 50% preceded by upper respiratory tract infectionAdults: 1/100,000Gender: male/female : 1.8/1Vasculature involved Gastrointestinal tract Kidney Glomerulonephritis(mesangial)Skin VasculitisSubmucosal arterioles/venulesDermal arterioles, capillaries, andpostcapillary venules38

Clinical Manifestations Abdominal pain (“purpura” of the smallbowel, i.e., submucosal hemorrhage) IntussusceptionHematuria/proteinuria Renal insufficiency infrequent Purpura Arthralgia/arthritisPathogenesis VasculitisActivation of the mucosal humoralimmune compartment resulting intissue (vascular) deposition of IgAcontaining immune complexes39

Purpura of the ButtocksSmall Vessel Dermal VasculitisVasculitis40

IgA Deposition in Dermal VasculatureHSP GlomerulonephritisVasculitis41

IgA Deposition in the MesangiumPrognosis of Henoch Schonlein Purpura Vasculitis90-95% of patients exhibit spontaneousremission after 3-4 weeks, with 20-30%experiencing short-term relapses withinthe following 6-12 months42

Treatment Supportive HydrationBed restAnalgesia Non-steroidal antiinflammatoryagentsVasculitisEdward Dwyer, M.D.Division of RheumatologyVasculitis43

Vasculitis 3 Classification of Vasculitis Small-sized Vessels(cont.) Immune-Complex mediated: 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