VASCULITISVASCULITIS

BLOOD VESSELS INFLAMMATIONBLOOD VESSELS INFLAMMATION

Primary vasculitisPrimary vasculitis

Secondary vasculitisSecondary vasculitis((infections, viruses, tumors, collagen diseasesinfections, viruses, tumors, collagen diseases::

RA, SjRA, Sjögren’s syndrome, SLE, SSc, Myositisögren’s syndrome, SLE, SSc, Myositis))

VASCULITISVASCULITISCLASSIFICATIONCLASSIFICATION

LARGE-MEDIUM-SIZED VESSELSLARGE-MEDIUM-SIZED VESSELS– Takayasu’s arteritisTakayasu’s arteritis– Temporal arteritisTemporal arteritis

MEDIUM-SMALL-SIZED VESSELSMEDIUM-SMALL-SIZED VESSELS– Polyarteritis nodosaPolyarteritis nodosa– Kawasaki’s diseaseKawasaki’s disease

– Churg-Strauss syndromeChurg-Strauss syndrome– Wegener’s granulematosisWegener’s granulematosis

SMALL-SIZED VESSELSSMALL-SIZED VESSELS– Schonlein-Henoch syndromeSchonlein-Henoch syndrome– CryoglobulinemiaCryoglobulinemia– Goodpasture’s )anti-GBM( diseaseGoodpasture’s )anti-GBM( disease– Immune complex vasculitis )SLE, Serum sickness(Immune complex vasculitis )SLE, Serum sickness(– Microscopic polyangiitisMicroscopic polyangiitis

VASCULITISVASCULITISCLASSIFICATIONCLASSIFICATION

MISCELLANEOUS SYNDROMESMISCELLANEOUS SYNDROMES

– Behcet’s syndromeBehcet’s syndrome

– Pyoderma gangrenosumPyoderma gangrenosum

VASCULITISVASCULITISPathogenesis - Immune complexes formationPathogenesis - Immune complexes formation

AgAg

AbAb

WBCWBC

Ag+Ab=ICAg+Ab=IC

CC

B-cell activationB-cell activation

RBCRBC

VASCULITISVASCULITISPathogenesis- Anti-neutrophile cytoplasmic AbPathogenesis- Anti-neutrophile cytoplasmic Ab

pANCA – myeloperoxidase cANCA-proteinase 3pANCA – myeloperoxidase cANCA-proteinase 3

VASCULITISVASCULITIS PathogenesisPathogenesis – granuloma formation– granuloma formation

T lymphocyte accumulationT lymphocyte accumulation

Takayasu’s ArteritisTakayasu’s ArteritisPulse-less diseasePulse-less disease

Incidence:Incidence: 2-5/1 000 000/year. 2-5/1 000 000/year.

Epidemiology:Epidemiology: children+young womenchildren+young womenJapan, India, Africa, Asia, South America, Europe, Japan, India, Africa, Asia, South America, Europe,

US.US.F:M=7:1. Age 10-50yearsF:M=7:1. Age 10-50years )90% <30y( )90% <30y(Pathology:Pathology: Involves aortic arch, descending aorta Involves aortic arch, descending aorta

and its branches + AV involvement, coronary and and its branches + AV involvement, coronary and pulmonary arteriespulmonary arteries

PanarteritisPanarteritis with with granulomagranuloma narrowed vessels and narrowed vessels and thrombusthrombus formation formation

Takayasu’s ArteritisTakayasu’s ArteritisClinical featuresClinical features::General:General: malaise, fever, weight loss, arthralgia/arthritis malaise, fever, weight loss, arthralgia/arthritisVascular:Vascular:

– arm claudication/numbness arm claudication/numbness – pulses changes/discrepancy pulses changes/discrepancy – hypertension hypertension – renal failure renal failure – Aortic regurgitation )AR(Aortic regurgitation )AR(

Laboratory:Laboratory: anemia, ESR/CRP elevation anemia, ESR/CRP elevationDiagnosis:Diagnosis: angiography, MRI angiography angiography, MRI angiographyTreatment:Treatment: steroids, cytotoxic drugs, control of steroids, cytotoxic drugs, control of

hypertension, arterial reconstruction, AVRhypertension, arterial reconstruction, AVRPrognosis: Prognosis: 15 year survival 90%15 year survival 90%

Takayasu’s ArteritisTakayasu’s Arteritis

Giant Cell Arteritis/Giant Cell Arteritis/Temporal arteritisTemporal arteritis

Polyarteritis Nodosa )PAN(Polyarteritis Nodosa )PAN(

Incidence: Incidence: 5-9 to 80/1 000 0005-9 to 80/1 000 000

EpidemiologyEpidemiology: M:F=2-3:1, young patients: M:F=2-3:1, young patients

Pathology:Pathology: fibrinoid necrosisfibrinoid necrosis, , aneurysms formationaneurysms formation,, Ly/Eos infiltration, lumen thrombosis, fibrous Ly/Eos infiltration, lumen thrombosis, fibrous obliteration of the lumenobliteration of the lumen

Primary or secondaryPrimary or secondary )RA, Sjogren’s syndrome, )RA, Sjogren’s syndrome,

SLE, SLE, Hepatitis B, Hepatitis C, HIV, FMFHepatitis B, Hepatitis C, HIV, FMF((

Polyarteritis NodosaPolyarteritis Nodosa

Clinical features:Clinical features:GeneralGeneral: weight loss, mild to high fever, malaise : weight loss, mild to high fever, malaise

Musculo-skeletalMusculo-skeletal: arthralgia, asymmetric : arthralgia, asymmetric polyarthritis, myalgia polyarthritis, myalgia

SkinSkin: palpable purpura, ulceration, ischemic : palpable purpura, ulceration, ischemic necrosisnecrosis

NeuralNeural: peripheral neuropathy, mononeuritis : peripheral neuropathy, mononeuritis multiplex, CVAmultiplex, CVA

Polyarteritis NodosaPolyarteritis NodosaGITGIT: abdominal pain, mesenteric thrombosis, : abdominal pain, mesenteric thrombosis,

peritonitis, bleedingperitonitis, bleeding

KidneyKidney: hypertension, renal failure, : hypertension, renal failure, proteinuria, hematuria – not proteinuria, hematuria – not glomerulonephritisglomerulonephritis

CardiacCardiac: CHF, MI: CHF, MI

LungLung: very rare hemorrhage: very rare hemorrhage

EyesEyes: retinal detachment, scleritis: retinal detachment, scleritis

Polyarteritis NodosaPolyarteritis Nodosa

Ischemic ulcersIschemic ulcers

Polyarteritis NodosaPolyarteritis Nodosa

Laboratory data:Laboratory data: ESRESR, anemia, anemia, globulins, globulins, ,

40% HBS Ag+, aHCV+,40% HBS Ag+, aHCV+, 20-30% pANCA+ , 20-30% pANCA+ , abnormal urineabnormal urine

DiagnosisDiagnosis: :

biopsybiopsy, , angiographyangiography

Aneurysms formationAneurysms formation

Polyarteritis NodosaPolyarteritis Nodosa

PrognosisPrognosis: 5 year survival 15%-80%: 5 year survival 15%-80%

TreatmentTreatment: :

Hepatitis negHepatitis neg: Steroids, : Steroids, Cyclophosphamide, Imuran, Cyclophosphamide, Imuran, MethotrexateMethotrexate

Hepatitis posHepatitis pos: Antiviral treatment : Antiviral treatment )Interferon, plasmapheresis, Ribaverin()Interferon, plasmapheresis, Ribaverin(

Churg-Strauss SyndromeChurg-Strauss Syndrome

Incidence: Incidence: 1-2/1 000 0001-2/1 000 000

EpidemiologyEpidemiology: M:F=2:1: M:F=2:1

Pathology:Pathology: allergic necrotizing angiitisallergic necrotizing angiitis, , eosinophils infiltrationeosinophils infiltration, extra-vascular , extra-vascular granulomas granulomas formationformation

Churg-Strauss SyndromeChurg-Strauss Syndrome

Prodromal periodProdromal period: : bronchial asthmabronchial asthma

Second phaseSecond phase: :

• eosinophiliaeosinophilia

• LLóóffler s-me - eosinophilic pneumonia ffler s-me - eosinophilic pneumonia

• eosinophilic gastroenteritiseosinophilic gastroenteritis

Third phaseThird phase: : systemic vasculitissystemic vasculitis

Churg-Strauss SyndromeChurg-Strauss Syndrome

Clinical features:Clinical features:• General signsGeneral signs: fever, malaise, weight loss: fever, malaise, weight loss• Lung involvementLung involvement: asthma, lung infiltrates: asthma, lung infiltrates• GIT involvementGIT involvement: abdominal pain, diarrhea, : abdominal pain, diarrhea,

bleedingbleeding• NS involvementNS involvement: neuropathy )motor/sensor(: neuropathy )motor/sensor(• Kidney involvementKidney involvement: GN : GN • ArthritisArthritis

Churg-Strauss SyndromeChurg-Strauss Syndrome

Peripheral lung infiltratesPeripheral lung infiltrates

Churg-Strauss SyndromeChurg-Strauss Syndrome

Laboratory dataLaboratory data: : anemia, ESRanemia, ESR , ,

5 000-10 000 eosinophils/mm5 000-10 000 eosinophils/mm33, IgE, IgE , , pANCA +pANCA + )70%( )70%(

DiagnosisDiagnosis: : biopsybiopsy

PrognosisPrognosis: 5 years survival-65%: 5 years survival-65%

TreatmentTreatment: : Steroids, Cyclophosphamide, Steroids, Cyclophosphamide, ImuranImuran

Wegener’s GranulematosisWegener’s Granulematosis

Incidence: Incidence: 4/1 000 0004/1 000 000

EpidemiologyEpidemiology: : M:F=1,2:1M:F=1,2:1

Pathology:Pathology: necrotizing granulomatosis and necrotizing granulomatosis and vasculitis, neutrophilsvasculitis, neutrophils accumulation: accumulation: upper airways, lungs, kidney upper airways, lungs, kidney

Wegener’s GranulematosisWegener’s GranulematosisClinical features:Clinical features:• General signsGeneral signs: fever, malaise, weight loss: fever, malaise, weight loss• Upper Respiratory TractUpper Respiratory Tract: sinusitis, otitis media, nasal : sinusitis, otitis media, nasal

ulcerationulceration• Low Respiratory TractLow Respiratory Tract: Pulmonary infiltrates, nodules, : Pulmonary infiltrates, nodules,

cavities )cough, dyspnea, hemopthysis(cavities )cough, dyspnea, hemopthysis(• KidneyKidney:: Glomerulonephritis, hypertension, renal Glomerulonephritis, hypertension, renal

failurefailure• PurpuraPurpuraNecrotic ulcersNecrotic ulcers• ArthritisArthritis )50-70%( )50-70%(• EyesEyes: orbital damage, scleritis )20%(: orbital damage, scleritis )20%(• NSNS: peripheral neuropathy, central )33%(: peripheral neuropathy, central )33%(• HeartHeart: CHF, MI, arrhythmias : CHF, MI, arrhythmias

Wegener’s GranulematosisWegener’s Granulematosis

Orbital and nasal granulomaOrbital and nasal granuloma

Pulmonary nodesPulmonary nodesAnd cavitationAnd cavitation

Wegener’s GranulematosisWegener’s Granulematosis

Laboratory dataLaboratory data: : leukocytosis, anemia, ESRleukocytosis, anemia, ESR, , cANCA + )90%(, abnormal urinecANCA + )90%(, abnormal urine

DiagnosisDiagnosis: : nasal biopsy, open lung biopsynasal biopsy, open lung biopsy

PrognosisPrognosis: 5 years survival - 50-75%: 5 years survival - 50-75%

TreatmentTreatment: : Steroids + CyclophosphamideSteroids + Cyclophosphamide, , Imuran, MTXImuran, MTX

Trimethoprim Sulfamethoxazole )Resprim(Trimethoprim Sulfamethoxazole )Resprim(

Henoch-SchHenoch-Schőőnlein Purpuranlein Purpura

Incidence: Incidence: 4-10/100 0004-10/100 000

EpidemiologyEpidemiology: M:F=1,2:1, 4-14 years: M:F=1,2:1, 4-14 years

Pathology:Pathology: necrotizing leukocytoclastic necrotizing leukocytoclastic vasculitis, fibrinoid necrosis, IC, vasculitis, fibrinoid necrosis, IC, IgA and IgA and C3 deposition (C3 deposition (skin, gut, kidney skin, gut, kidney [glomerrular& tubular][glomerrular& tubular](,(, MNC infiltration MNC infiltration

Henoch-SchHenoch-Schőőnlein Purpuranlein Purpura

Clinical features:Clinical features:• General signsGeneral signs• Skin: Skin: purpura purpura )100%(, ulceration )rare()100%(, ulceration )rare(• ArthritisArthritis, arthralgia )60%(, arthralgia )60%(• GIT vasculitisGIT vasculitis )85%-abd. pain, diarrhea, )85%-abd. pain, diarrhea,

bleeding( bleeding( • Renal )IgA nephropathy( disease )10-40%( – Renal )IgA nephropathy( disease )10-40%( –

segmental proliferative GNsegmental proliferative GN +/- crescents, IgA + +/- crescents, IgA +

CC³³ deposition )Berger’s disease( – hematuria, deposition )Berger’s disease( – hematuria, proteinuriaproteinuria

Henoch-SchHenoch-Schőőnlein Purpuranlein Purpura

Purpura, ArthritisPurpura, Arthritis Ischemic colitisIschemic colitis

Henoch-SchHenoch-Schőőnlein Purpuranlein Purpura

Laboratory data:Laboratory data: elevated ESR/CRP, leukocytosis, elevated ESR/CRP, leukocytosis, mild anemia, hematuria, high IgAmild anemia, hematuria, high IgA

DiagnosisDiagnosis: : clinical +/- biopsyclinical +/- biopsy

Prognosis:Prognosis: good good (except severe GIT vasculitis and IgA (except severe GIT vasculitis and IgA nephropathy)nephropathy)

TreatmentTreatment: : rest, NSAID, Steroids, Cyclophosphamiderest, NSAID, Steroids, Cyclophosphamide

Cryoglobulinemic VasculitisCryoglobulinemic VasculitisImmunoglobulins – reversibly precipitated by low Immunoglobulins – reversibly precipitated by low

temperaturetemperature

Type 1 - 25%Type 1 - 25%Type 2 - 25%Type 2 - 25%Type 3 - 50%Type 3 - 50%

MonoclonalMonoclonal

IgM or IgGIgM or IgG

Monoclonal Monoclonal mixedmixed

RF )IgM to IgG(RF )IgM to IgG(

PolyclonalPolyclonal

mixedmixed

RF )IgM to IgG(RF )IgM to IgG(

MyelomaMyeloma WaldenstrWaldenström d-seöm d-se

LymphomaLymphoma

Collagen diseaseCollagen disease

InfectionsInfections

LymphomaLymphoma

RA, SLE, SS, DMRA, SLE, SS, DM

SBE, Strept GNSBE, Strept GN

Hepatitis C/BHepatitis C/B

Cryoglobulinemic VasculitisCryoglobulinemic Vasculitis• Hyperviscosity problems:Hyperviscosity problems:

– visual problems visual problems – TIATIA– neuropathyneuropathy

• Vasculitis: Vasculitis: – purpurapurpura– arthritisarthritis– kidney involvementkidney involvement

• glomerulonephritis glomerulonephritis • progressive renal failure progressive renal failure • nephrotic syndromenephrotic syndrome

Cryoglobulinemic VasculitisCryoglobulinemic VasculitisLaboratory data: Laboratory data: anemia, high ESR/CRP, anemia, high ESR/CRP,

hyperglobulinemia, hyperglobulinemia, pos cryoglobulinspos cryoglobulins, elevated , elevated creatinine, hematuria, proteinuria, liver enzymes creatinine, hematuria, proteinuria, liver enzymes elevation - elevation - pos anti pos anti HCV/HBV/HIVHCV/HBV/HIV Ab Ab

Diagnosis:Diagnosis: biopsy )leukocytoclastic vasculitis( with biopsy )leukocytoclastic vasculitis( with deposits of cryoglobulins, cryoglobulins, DPGNdeposits of cryoglobulins, cryoglobulins, DPGN

Prognosis:Prognosis: poorpoor

TreatmentTreatment: : plasmapheresis, antiviral therapy plasmapheresis, antiviral therapy )Ribaverin + Interferon )Ribaverin + Interferon (, Steroids + (, Steroids + CyclophosphamideCyclophosphamide

Behcet’s DiseaseBehcet’s DiseaseEpidemiology: Japan, Meddle East )Silk rood(Epidemiology: Japan, Meddle East )Silk rood(Family penetrationFamily penetration

Clinical featureClinical feature::• Oral aphthous ulcersOral aphthous ulcers )100%( – 3/year )100%( – 3/year • Genital ulcerationsGenital ulcerations )80%( )80%(• Eye inflammation )65%(-anterior/posterior Eye inflammation )65%(-anterior/posterior

uveitis, retinal vasculitisuveitis, retinal vasculitis• Skin inflammation )70%(-)folliculitis-like, Skin inflammation )70%(-)folliculitis-like,

acne-like, acne-like, erythema nodosumerythema nodosum-like( -like( • Vasculitis Vasculitis )arterial-CNS, venous – thrombosis )arterial-CNS, venous – thrombosis

superficial and deep(superficial and deep(

Behcet’s DiseaseBehcet’s Disease

AphthaAphtha

Erythema nodosumErythema nodosum HypopionHypopion

Behcet’s DiseaseBehcet’s Disease

Laboratory dataLaboratory data: : HLA BHLA B5151 pos pos . .

Pathergy skin testPathergy skin testPrognosisPrognosis: : serious in uveitis - blindness, CNS serious in uveitis - blindness, CNS vasculitis, thrombosisvasculitis, thrombosisTreatmentTreatment:: Colchicine Colchicine

CS +/- MTX, Imuran, SalazopyrineCS +/- MTX, Imuran, Salazopyrine CS +NeoralCS +Neoral ThalidomideThalidomide

AnticoagulantsAnticoagulants

Pyoderma GangrenosumPyoderma GangrenosumNeutrophilic DermatosisNeutrophilic Dermatosis

Inflammatory BowelInflammatory Bowel

DiseasesDiseases::

Crohn’s DiseaseCrohn’s Disease

Ulcerative colitisUlcerative colitis

MyeloproliferativeMyeloproliferative

DiseasesDiseases::

Polycythemia VeraPolycythemia Vera

MyelomaMyeloma

LeukemiasLeukemias