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.