PRIMARY PRIMARY VASCULITIDESVASCULITIDES

Amy Shultz, M.D.Amy Shultz, M.D.

VASCULITIS DEFINITIONVASCULITIS DEFINITION

Presence of WBCs in vessel wall with Presence of WBCs in vessel wall with reactive damage of mural structuresreactive damage of mural structures

Leads to bleeding, tissue Leads to bleeding, tissue ischemia/necrosisischemia/necrosis

Primary—idiopathicPrimary—idiopathic Secondary—to another underlying diseaseSecondary—to another underlying disease

(SLE, RA, cryglobulinemia)(SLE, RA, cryglobulinemia)

HISTORYHISTORY

1866: Kussmaul & Maier—described 1866: Kussmaul & Maier—described nodular inflammation of muscular arteriesnodular inflammation of muscular arteries

Termed periarteritis nodosa—later Termed periarteritis nodosa—later changed to polyarteritis nodosa (PAN)changed to polyarteritis nodosa (PAN)

PATHOGENESISPATHOGENESIS

Remains largely unknownRemains largely unknown Hypothesis: (Hypothesis: (Most likely multifactorial)Most likely multifactorial)

--Immune complex deposition/humoral responsesImmune complex deposition/humoral responses

- Pathogenic T cell responses and granuloma formation- Pathogenic T cell responses and granuloma formation

- Autoantibodies- Autoantibodies

- Cytokine activation- Cytokine activation

- Infectious trigger—bacteria, mycobacteria, viruses- Infectious trigger—bacteria, mycobacteria, viruses

- Drugs- Drugs

- Genetic predisposition- Genetic predisposition

VASCULITIDESVASCULITIDES

Fairly rare diseasesFairly rare diseases

Presentation: highly variable making delays in Presentation: highly variable making delays in diagnosis commondiagnosis common

High morbidity and mortalityHigh morbidity and mortality

Therapeutic challenge often requiring prolonged Therapeutic challenge often requiring prolonged & intensive immunosuppression.& intensive immunosuppression.

CLASSIFICATIONCLASSIFICATION

Individual diseases affect blood vessels of Individual diseases affect blood vessels of a particular size—clinical manifestations a particular size—clinical manifestations and wide range of disease severity.and wide range of disease severity.

Large Vessel Vasculitis:Large Vessel Vasculitis: Takayasu arteritisTakayasu arteritis Giant cell arteritisGiant cell arteritis

CLASSIFICATIONCLASSIFICATION

Medium vessel vasculitis:Medium vessel vasculitis: Polyarteritis nodosaPolyarteritis nodosa Kawasaki disease (children)Kawasaki disease (children)

Small vessel vasculitis:Small vessel vasculitis: Churg-Strauss syndromeChurg-Strauss syndrome Wegener’s granulomatosisWegener’s granulomatosis Microscopic polyangiitisMicroscopic polyangiitis

TAKAYASU ARTERITIS (TA)TAKAYASU ARTERITIS (TA)

Chronic granulomatous vasculitis that affects the Chronic granulomatous vasculitis that affects the aorta, its main branches, and pulmonary arteriesaorta, its main branches, and pulmonary arteries

Women affected in 80-90% of casesWomen affected in 80-90% of cases

Age of onset: 10-40 yearsAge of onset: 10-40 years

Worldwide distribution, but greatest prevalence in Worldwide distribution, but greatest prevalence in Asians.Asians.

U.S. incidence rate: 2.6/millionU.S. incidence rate: 2.6/million

TA TA (CLINICAL MANIFESTATIONS)(CLINICAL MANIFESTATIONS)

Systemic symptoms:Early phaseSystemic symptoms:Early phase FatigueFatigue MalaiseMalaise Weight lossWeight loss Night sweatsNight sweats Fever-low gradeFever-low grade Arthralgias~ 55%Arthralgias~ 55% MyalgiasMyalgias

TA TA (CLINICAL MANIFESTATIONS)(CLINICAL MANIFESTATIONS)

Vascular compromise: Late phaseVascular compromise: Late phase Aneurysm formation and ruptureAneurysm formation and rupture Vessel stenosis/occlusion--ischemiaVessel stenosis/occlusion--ischemia Catastrophic complications:Catastrophic complications:

Aortic dissection/ruptureAortic dissection/rupture Aortic valve regurgitationAortic valve regurgitation CVACVA Hypertensive crisisHypertensive crisis MIMI

ARTERYARTERY MANIFESTATION MANIFESTATION

SubclavianSubclavian Common carotidCommon carotid RenalRenal Aortic arch/rootAortic arch/root VertebralVertebral PulmonaryPulmonary CoronaryCoronary

Arm claudicationArm claudication Visual changes, syncope, Visual changes, syncope,

TIA, CVA, headachesTIA, CVA, headaches HTN, renal failureHTN, renal failure AI, CHFAI, CHF Visual changes, dizzinessVisual changes, dizziness Dyspnea, hemoptysisDyspnea, hemoptysis Chest pain, MIChest pain, MI

TA TA (HISTOPATHOLOGY)(HISTOPATHOLOGY)

Cell-mediated mechanisms:Cell-mediated mechanisms: Infiltrating cells mainly consist of killer cells Infiltrating cells mainly consist of killer cells

and gamma delta T lymphocytesand gamma delta T lymphocytes

All layers of large arteries affected:All layers of large arteries affected: InflammationInflammation Granuloma formationGranuloma formation Giant cellsGiant cells

TA TA (PHYSICAL EXAMINATION)(PHYSICAL EXAMINATION)

Asymmetric blood pressure measurementsAsymmetric blood pressure measurements Diminished pulses/pulselessDiminished pulses/pulseless Bruits-subclavian, carotid, brachial, abdBruits-subclavian, carotid, brachial, abd HTN- RAS or decreased elasticity of aortaHTN- RAS or decreased elasticity of aorta Decreased hair growth, cool extremities, Decreased hair growth, cool extremities,

muscle wasting, gangrenous digitsmuscle wasting, gangrenous digits

TATA (LAB ABNORMALITIES)(LAB ABNORMALITIES)

Nonspecific:Nonspecific: Elevated ESRElevated ESR Elevated CRPElevated CRP Normochromic, normocytic anemiaNormochromic, normocytic anemia HypoalbuminemiaHypoalbuminemia

Autoantibodies:Autoantibodies: Antiendothelial cell (recent studies value?)Antiendothelial cell (recent studies value?) ANA, ANCA, anti-DNA, APL: negativeANA, ANCA, anti-DNA, APL: negative

TA TA (IMAGING)(IMAGING)

Angiography usually necessary to confirm Angiography usually necessary to confirm diagnosis and see extent of disease:diagnosis and see extent of disease: Advantage: Advantage: Provides clear outline of involved arteries Provides clear outline of involved arteries

& luminal patency& luminal patency Disadvantage: Disadvantage: Does not show arterial thickening, Does not show arterial thickening,

invasive, & large dye loadinvasive, & large dye load

Helical CT angiography and MRAHelical CT angiography and MRA Becoming more popularBecoming more popular Used to access continued disease activityUsed to access continued disease activity Shows thickness and edema within wallShows thickness and edema within wall

TA TA (CLASSIFICATION CRITERIA)(CLASSIFICATION CRITERIA)

• Age of onset <40Age of onset <40• Claudication of extremitiesClaudication of extremities• Decreased pulsation in 1 or both brachialsDecreased pulsation in 1 or both brachials• >10mmHg SBP difference between arms>10mmHg SBP difference between arms• Bruit over 1 or both subclavian or abd. AortaBruit over 1 or both subclavian or abd. Aorta• Angiographic narrowing of aorta or branchesAngiographic narrowing of aorta or branches

• Patients must meet at least 3 of the 6 criteriaPatients must meet at least 3 of the 6 criteria

TA TA (TREATMENT)(TREATMENT)

Corticosteroids: Corticosteroids: 60mg/day gradually tapered60mg/day gradually tapered

Cytotoxic drugs: Chronic active disease (50%)Cytotoxic drugs: Chronic active disease (50%) Methotrexate—17.5-25mg/weekMethotrexate—17.5-25mg/week Azathioprine—2mg/kg/dayAzathioprine—2mg/kg/day

Anti-TNF agents: clinical trials ongoingAnti-TNF agents: clinical trials ongoing Revascularization: bypass grafts vs. PTCARevascularization: bypass grafts vs. PTCA

GIANT CELL ARTERITIS (GCA)GIANT CELL ARTERITIS (GCA)

Granulomatous vasculitis affecting extra-Granulomatous vasculitis affecting extra-cranial branches of arteries from the aortic cranial branches of arteries from the aortic archarch

Most common systemic vasculitis: Most common systemic vasculitis: prevalence 200 per 100,000prevalence 200 per 100,000

Occurs almost exclusively over 50 yrs of Occurs almost exclusively over 50 yrs of ageage

Female:male ratio 2:1Female:male ratio 2:1

PATHOGENESISPATHOGENESIS

Cell-mediated immune responseCell-mediated immune response against against antigens in arterial wall.antigens in arterial wall. Granulomatous inflammationGranulomatous inflammation T cells secreting IL-2 & interferon T cells secreting IL-2 & interferon γγ

Humoral response against antigens in the Humoral response against antigens in the arterial wall.arterial wall. Immunoglobulin and complement deposits.Immunoglobulin and complement deposits.

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

In most cases insidious onset of In most cases insidious onset of symptoms:symptoms: FatigueFatigue FeverFever Weight lossWeight loss anorexiaanorexia

Headache most common symptom: Headache most common symptom: lacinating localized to regions along lacinating localized to regions along arteries in the scalp.arteries in the scalp.

GCA GCA (CLINICAL MANIFESTATIONS)(CLINICAL MANIFESTATIONS)

HeadacheHeadache Weight loss/anorexiaWeight loss/anorexia Jaw claudicationJaw claudication FeverFever Malaise/fatigueMalaise/fatigue PMRPMR Transient visual symptomTransient visual symptom SynovitisSynovitis Fixed visual symptomFixed visual symptom

68%68% 50%50% 45%45% 42%42% 40%40% 39%39% 16%16% 15%15% 14%14%

GCA GCA (PE AND LAB)(PE AND LAB)

Physical exam: Nodularity, tenderness, Physical exam: Nodularity, tenderness, absent pulsations, bruits of involved absent pulsations, bruits of involved arteriesarteries

Fundoscopic examination in patients with Fundoscopic examination in patients with visual loss: pale, swollen disc with blurred visual loss: pale, swollen disc with blurred marginsmargins

Lab: Markedly elevated ESRLab: Markedly elevated ESR

GCA GCA (DIAGNOSIS)(DIAGNOSIS)

Clinical Suspicion: Clinical Suspicion: Elderly patient with Elderly patient with headache, visual symptoms, and high ESRheadache, visual symptoms, and high ESR

Diagnosis confirmed by temporal artery biopsy: Diagnosis confirmed by temporal artery biopsy: Shows panmural mononuclear cell infiltration with Shows panmural mononuclear cell infiltration with

granulomas and giant cellsgranulomas and giant cells

Treatment should be instituted promptly while Treatment should be instituted promptly while biopsy is arrangedbiopsy is arranged

GCA GCA (TREATMENT)(TREATMENT)

Prednisone 40 to 60mg/day: initial dosePrednisone 40 to 60mg/day: initial dose In patients with acute visual loss: Solu-In patients with acute visual loss: Solu-

medrol 1g/day x 3 daysmedrol 1g/day x 3 days Steroids can be tapered after clinical Steroids can be tapered after clinical

remission achieved: remission achieved: ESR and CRP normalizedESR and CRP normalized

Most patients off steroids by 2 years. Most patients off steroids by 2 years. Relapse rate 26-90% (highly variable).Relapse rate 26-90% (highly variable).

Methotrexate studied in 2 RCT: Methotrexate studied in 2 RCT: conflicting conflicting results in ability to decrease relapse & steroid usageresults in ability to decrease relapse & steroid usage

GCAGCA( ( Follow-up)Follow-up)

Thoracic aortic aneurysms: Thoracic aortic aneurysms: Late manifestationLate manifestation

GCA patients 17 times more likely than age GCA patients 17 times more likely than age and sex matched people to develop theseand sex matched people to develop these

Yearly chest x-rays are recommended for up Yearly chest x-rays are recommended for up to 10 years to identify patients with to 10 years to identify patients with aneurysms prior to rupture.aneurysms prior to rupture.

POLYARTERITIS NODOSAPOLYARTERITIS NODOSA (PAN) (PAN)

Systemic panmural necrotizing vasculitis Systemic panmural necrotizing vasculitis typically affecting small and medium-sized typically affecting small and medium-sized arteries—fibrinoid necrosisarteries—fibrinoid necrosis

Most cases are idiopathicMost cases are idiopathic 7 to 22% of cases associated with 7 to 22% of cases associated with

hepatitis B infectionhepatitis B infection: must be r/o in all patients: must be r/o in all patients

Smaller percentage found in hairy cell Smaller percentage found in hairy cell leukemia, hepatitis C, and HIVleukemia, hepatitis C, and HIV

Classical PAN: ANCA negative Classical PAN: ANCA negative

PAN EPIDEMIOLOGYPAN EPIDEMIOLOGY

Incidence: 0.7/100,000Incidence: 0.7/100,000 Male:female Male:female ~ 2:1~ 2:1 Seen in all ages--peak 40-60 years of ageSeen in all ages--peak 40-60 years of age

May range in severity from mild limited to May range in severity from mild limited to 1 organ system to fulminate multisystem 1 organ system to fulminate multisystem involvement.involvement.

PANPAN (CLINICAL MANIFESTATIONS) (CLINICAL MANIFESTATIONS)

Systemic symptoms: fatigue, weakness, Systemic symptoms: fatigue, weakness, fever, arthalgias, myalgias fever, arthalgias, myalgias (60-70%)(60-70%)

PNS: Mononeuritis multiplex—PNS: Mononeuritis multiplex—motor & motor & sensory deficits sensory deficits (50-70%)(50-70%)

Skin:Skin: livedo reticularis, digital necrosis, skin ulcers, livedo reticularis, digital necrosis, skin ulcers, bullous eruptions, nodules, palpable purpura (45-60%)bullous eruptions, nodules, palpable purpura (45-60%)

Renal: Renal: Extra-glomerular vasculopathy mostly some Extra-glomerular vasculopathy mostly some GN—renal insufficiency, hypertension, and renal GN—renal insufficiency, hypertension, and renal infarction (40-70%)infarction (40-70%)

PANPAN(CLINICAL (CLINICAL MANIFESTATIONS)MANIFESTATIONS)

GI:GI:(30-50%)(30-50%)Mesenteric arteritisMesenteric arteritisischemiaischemia StomachStomach IntestinesIntestines LiverLiver GallbladderGallbladder

Orchitis: rare seen more with HBVOrchitis: rare seen more with HBV Lab: non-specific (95%)Lab: non-specific (95%)

↑↑ESRESR Normochromic/normocytic anemia Normochromic/normocytic anemia ThrombocytosisThrombocytosis ↓albumin↓albumin

PANPAN(DIAGNOSIS)(DIAGNOSIS)

Visceral/renal angiography: Visceral/renal angiography: microaneurysms, ectasia, stenoses in medium-microaneurysms, ectasia, stenoses in medium-sized vesselssized vessels

Biopsy:Biopsy: peripheral nerve or skin—focal peripheral nerve or skin—focal segmental necrotizing vasculitis with mixed cell segmental necrotizing vasculitis with mixed cell infiltrate and no granulomata affecting medium-infiltrate and no granulomata affecting medium-sized arteries.sized arteries.

PANPAN(PROGNOSIS)(PROGNOSIS)

Untreated: 13% 5 year survival rateUntreated: 13% 5 year survival rate Main causes of death: renal failure, Main causes of death: renal failure,

mesenteric, cardiac, cerebral infarctionmesenteric, cardiac, cerebral infarction Five-factor score: Five-factor score: French vasculitis groupFrench vasculitis group

Proteinuria >1g/dayProteinuria >1g/day GI bleeding, perforation, infarct, pancreatitisGI bleeding, perforation, infarct, pancreatitis Renal insufficiencyRenal insufficiency CardiomyopathyCardiomyopathy CNS involvementCNS involvement

PANPAN(TREATMENT)(TREATMENT)

Prednisone 1mg/kg/dayPrednisone 1mg/kg/dayCyclophosphamide 2mg/kg + steroidsCyclophosphamide 2mg/kg + steroidsAzathioprine 2mg/kg + steroidsAzathioprine 2mg/kg + steroidsOptimal duration of therapy is Optimal duration of therapy is

unknown.unknown.

Relapse rateRelapse rate~40%~40%If Hep B present, must treat.If Hep B present, must treat.

ANCA-ASSOCIATED VASCULITISANCA-ASSOCIATED VASCULITIS

Antineutrophilic cytoplasmic antibodies:Antineutrophilic cytoplasmic antibodies: C-ANCA (cytoplamic pattern) antigen—C-ANCA (cytoplamic pattern) antigen—

proteinase-3proteinase-3 P-ANCA (perinuclear pattern) antigen—P-ANCA (perinuclear pattern) antigen—

myeloperoxidasemyeloperoxidase

Binding of C-ANCA & P-ANCA to their antigen Binding of C-ANCA & P-ANCA to their antigen targets in neutrophils targets in neutrophils →→degranulation, degranulation, respiratory burst, NO production, respiratory burst, NO production, chemotaxischemotaxis→contributes to vascular damage.→contributes to vascular damage.

CHURG-STRAUSS SYNDROMECHURG-STRAUSS SYNDROME

Allergic granulomatosis & angiitis Allergic granulomatosis & angiitis characterized by:characterized by: Allergic rhinitisAllergic rhinitis AsthmaAsthma Peripheral blood eosinophiliaPeripheral blood eosinophilia Systemic vasculitisSystemic vasculitis

Slight male predominanceSlight male predominance Mean age at diagnosis: 40 yearsMean age at diagnosis: 40 years

CHURG-STRAUSSCHURG-STRAUSS(CLINICAL FEATURES)(CLINICAL FEATURES)

Prodromal phase: 2Prodromal phase: 2ndnd to 3 to 3rdrd decades of life decades of life—atopic disease, allergic rhinitis, asthma—atopic disease, allergic rhinitis, asthma

Eosinophilic phase: Peripheral blood Eosinophilic phase: Peripheral blood eosinophilia and infiltration of multiple eosinophilia and infiltration of multiple organs especially lungs and GI tractorgans especially lungs and GI tract

Vasculitic phase: 3Vasculitic phase: 3rdrd to 4 to 4thth decades of life decades of life—systemic vasculitis—systemic vasculitis

CHURG-STRAUSSCHURG-STRAUSS(CLINICAL FEATURES)(CLINICAL FEATURES)

Asthma—98-100%Asthma—98-100% Mononeuritis multiplex—50-80%Mononeuritis multiplex—50-80% Skin: Skin: palpable purpura, rash, tender palpable purpura, rash, tender

subcutaneous nodules (50-80%)subcutaneous nodules (50-80%) SinusitisSinusitis—20-70%—20-70% CV—pericarditisCV—pericarditis, CHF, MI (35-50%), CHF, MI (35-50%) GI—eosinophilic gastritis:GI—eosinophilic gastritis:pain, pain,

bleeding, colitis (30-60%)bleeding, colitis (30-60%)

CHURG-STRAUSSCHURG-STRAUSS(CLINICAL FEATURES)(CLINICAL FEATURES)

Renal—focal segmental GN (10-50%) less Renal—focal segmental GN (10-50%) less common than in WG or MPAcommon than in WG or MPA

Pulmonary infiltrates-40-75%Pulmonary infiltrates-40-75% Transient patchy infiltratesTransient patchy infiltrates Pulmonary hemorrhagePulmonary hemorrhage Bilateral, nodular disease without cavitationBilateral, nodular disease without cavitation Pleural effusions: exudative & rich in Pleural effusions: exudative & rich in

eosinophilseosinophils

CHURG-STRAUSSCHURG-STRAUSS(LAB ABNORMALITIES)(LAB ABNORMALITIES)

Peripheral eosinophilia >10%Peripheral eosinophilia >10% Elevated IgE levelsElevated IgE levels P-ANCA/anti-MPO—70%P-ANCA/anti-MPO—70% Elevated ESRElevated ESR Normochromic/normocytic anemiaNormochromic/normocytic anemia BAL—high percentage of eosinophilsBAL—high percentage of eosinophils

CHURG-STRAUSS CHURG-STRAUSS (DIAGNOSIS)(DIAGNOSIS)

• Confirmed by surgical lung biopsy or Confirmed by surgical lung biopsy or biopsy of other affected tissues:biopsy of other affected tissues:• Eosinophilic infiltratesEosinophilic infiltrates• Extensive areas of fibrinoid necrosisExtensive areas of fibrinoid necrosis• Giant cell vasculitis of small arteries and Giant cell vasculitis of small arteries and

veinsveins• Necrotizing granulomasNecrotizing granulomas

CHURG-STRAUSS CHURG-STRAUSS (TREATMENT)(TREATMENT)

Corticosteroids 1mg/kg/day until disease Corticosteroids 1mg/kg/day until disease resolution.resolution. Normalization of eosinophil count and ESRNormalization of eosinophil count and ESR

Severe, fulminant disease—Severe, fulminant disease—cyclophosphamide, azathioprinecyclophosphamide, azathioprine

Prior to use of steroids: uniformly fatalPrior to use of steroids: uniformly fatal 5 year survival—70%5 year survival—70%

WEGENER’S GRANULOMATOSIS(WG)WEGENER’S GRANULOMATOSIS(WG)

Necrotizing, granulomatous vasculitis Necrotizing, granulomatous vasculitis affecting small & medium-sized vesselsaffecting small & medium-sized vessels

Predilection for upper & lower respiratory Predilection for upper & lower respiratory tracts & kidneystracts & kidneys

Occurs at any age Occurs at any age peak 4peak 4thth to 5 to 5thth decades decades Men and women affected equallyMen and women affected equally May be indolent or rapidly progressiveMay be indolent or rapidly progressive Upper airway disease most common Upper airway disease most common

presenting featurepresenting feature

WG WG (CLINICAL MANIFESTATIONS)(CLINICAL MANIFESTATIONS)

• Pulmonary:Pulmonary: cough, pleuritis, hemoptysis, cough, pleuritis, hemoptysis, dyspnea (70-95%)dyspnea (70-95%)

• Upper airway: nasal ulcers, epistaxis, sinusitis, Upper airway: nasal ulcers, epistaxis, sinusitis, otitis, hearing inpairment, destructive otitis, hearing inpairment, destructive lesions/deformitities from cartilaginous ischemia lesions/deformitities from cartilaginous ischemia (70-95%)(70-95%)

• Renal: FS crescentic GN with no immune Renal: FS crescentic GN with no immune complexes, ARF (50-85%)complexes, ARF (50-85%)

WG WG (CLINICAL MANIFESTATIONS)(CLINICAL MANIFESTATIONS)

Tracheobronchial: subglottic stenosis, bronchial Tracheobronchial: subglottic stenosis, bronchial stenosis, hemorrhage (10-55%)stenosis, hemorrhage (10-55%)

Skin: purpura, ulcers, vesicles (45-60%)Skin: purpura, ulcers, vesicles (45-60%)

MS: arthalgias, myalgias, arthritis (30-70%)MS: arthalgias, myalgias, arthritis (30-70%)

Ocular: conjunctivitis, uveitis, corneal ulcers, Ocular: conjunctivitis, uveitis, corneal ulcers, retinal vasculitis, proptosis retinal vasculitis, proptosis (25-55%)(25-55%)

WG (WG (RADIOGRAPHIC FINDINGS)RADIOGRAPHIC FINDINGS)

Abnormal chest x-ray: 85-100%Abnormal chest x-ray: 85-100% NodulesNodules Bilateral patchy infiltratesBilateral patchy infiltrates Localized consolidationsLocalized consolidations Cavitary disease: culture to r/o Cavitary disease: culture to r/o

fungal/mycobacteriafungal/mycobacteria Bilateral disease more common than unilateralBilateral disease more common than unilateral CT of sinuses should be done to evaluate extent CT of sinuses should be done to evaluate extent

of disease of disease

WG WG (LAB ABNORMALITIES)(LAB ABNORMALITIES)

c-ANCA/anti-PR3: 85-90% active disease: c-ANCA/anti-PR3: 85-90% active disease: usually parallels disease courseusually parallels disease course

ESR: 90-95mm/hESR: 90-95mm/h Elevated CRPElevated CRP RF positive: 50-60%RF positive: 50-60% Microscopic hematuria, rbc casts, Microscopic hematuria, rbc casts,

proteinuriaproteinuria

WG WG (DIAGNOSIS)(DIAGNOSIS)

Confirmed by tissue biopsy at site of active Confirmed by tissue biopsy at site of active diseasedisease Small & medium vessel vasculitisSmall & medium vessel vasculitis Necrotizing granulomataNecrotizing granulomata Inflammatory infiltrateInflammatory infiltrate

• Special stains & cultures should be done to Special stains & cultures should be done to exclude infectious processes that produce exclude infectious processes that produce granulomasgranulomas

WG WG (TREATMENT)(TREATMENT)

Aggressive immunotherapy justified: Aggressive immunotherapy justified: untreated 90% of patients die in 2 yearsuntreated 90% of patients die in 2 years

Cyclophosphamide 2mg/kg/day + Cyclophosphamide 2mg/kg/day + prednisone 1mg/kg/dayprednisone 1mg/kg/day

Nonrandomized prospective studies with Nonrandomized prospective studies with mean f/u 8 years:mean f/u 8 years: Survival: 80%Survival: 80% Clinical improvement: 90%Clinical improvement: 90% Remission: 75% median time 12 monthsRemission: 75% median time 12 months

WGWG (TREATMENT) (TREATMENT)

Once remission is induced, substitute less Once remission is induced, substitute less toxic agents for cyclophosphamidetoxic agents for cyclophosphamide Toxicities: amenorrhea, infertility, cystitis, Toxicities: amenorrhea, infertility, cystitis,

bladder ca, myelodysplasia, & lymphomabladder ca, myelodysplasia, & lymphoma

Maintenance agents: Maintenance agents: Methotrexate 20 to 25mg/week if Cr <2.0Methotrexate 20 to 25mg/week if Cr <2.0 Azathioprine 2mg/kg/dayAzathioprine 2mg/kg/day Reduce steroids Reduce steroids

MICROSCOPIC POLYANGIITISMICROSCOPIC POLYANGIITIS

Systemic, necrotizing vasculitis affecting Systemic, necrotizing vasculitis affecting venules, arterioles, & capillaries. No venules, arterioles, & capillaries. No granulomasgranulomas

Prodromal phase: weight loss, fatigue, Prodromal phase: weight loss, fatigue, fevers, arthalgias, myalgias, or hemoptysisfevers, arthalgias, myalgias, or hemoptysis

100% of patients get RPGN100% of patients get RPGN p-ANCA/anti-MPO: 75%p-ANCA/anti-MPO: 75% Treatment: similar to Wegner’sTreatment: similar to Wegner’s

REFERENCESREFERENCES

Frankel, SK. Vasculitis: Wegner’s Frankel, SK. Vasculitis: Wegner’s Granulomatosis, Churg-Strauss Syndrome, Granulomatosis, Churg-Strauss Syndrome, Microscopic Polyangiitis, Polyarteritis Nodosa, Microscopic Polyangiitis, Polyarteritis Nodosa, and Takayasu arteritis. Critical Care Clinics. Oct. and Takayasu arteritis. Critical Care Clinics. Oct. 2002. Vol. 18.2002. Vol. 18.

Langford, CA. Vasculitis. Journal of Allergy and Langford, CA. Vasculitis. Journal of Allergy and Clinical Immunology. Feb. 2003 Vol. 111.Clinical Immunology. Feb. 2003 Vol. 111.

Rasmussen, JD. A Randomized Trial of Rasmussen, JD. A Randomized Trial of Maintenance Therapy for Vasculitis Associated Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies. with Antineutrophil Cytoplasmic Autoantibodies. N Engl J MED 2003; 349-36.N Engl J MED 2003; 349-36.

REFERENCESREFERENCES

• Conn, DL. Polyarteritis. In: Rheumatology, Conn, DL. Polyarteritis. In: Rheumatology, Klipper, JH, Dieppe, PA, Mosby, St. Louis, 1994.Klipper, JH, Dieppe, PA, Mosby, St. Louis, 1994.

• D’Cruz, DP. Difficult Asthma or Churg-Strauss D’Cruz, DP. Difficult Asthma or Churg-Strauss Syndrome? BMJ 1999; 318:475.Syndrome? BMJ 1999; 318:475.

• Langford, CA. Chronic Immunosuppressive Langford, CA. Chronic Immunosuppressive Therapy for Systemic Vasculitis. Curr Opin Therapy for Systemic Vasculitis. Curr Opin Rheumatol 1997; 9:41.Rheumatol 1997; 9:41.