The Vasculitis The Vasculitis SyndromesSyndromes

DefinitionDefinition Inflammation and damage of blood Inflammation and damage of blood

vesselsvessels Single organ→ skinSingle organ→ skin Several organ systemsSeveral organ systems PrimaryPrimary SecondarySecondary HeterogeneityHeterogeneity OverlapOverlap

Primary Vasculitis Primary Vasculitis SyndromesSyndromes

WegenerWegener´́s granulomatosiss granulomatosis Churg-Strauss syndromeChurg-Strauss syndrome Polyarteritis nodosaPolyarteritis nodosa Microscopic polyangitisMicroscopic polyangitis Giant cell arteritisGiant cell arteritis TakayasuTakayasu´́s arteritiss arteritis Henoch-Schönlein purpuraHenoch-Schönlein purpura Idiopthic cutaneous vasculitisIdiopthic cutaneous vasculitis Essential mixed cryoglobulinemiaEssential mixed cryoglobulinemia BehcetBehcet´́s syndromes syndrome Isolated vasculitis of the CNSIsolated vasculitis of the CNS CoganCogan´́s syndromes syndrome Kawasaki diseaseKawasaki disease

Secondary Vasculitis Secondary Vasculitis SyndromesSyndromes

Drug-induced vasculitisDrug-induced vasculitis Serum sicknessSerum sickness Vasculitis associted with other primary Vasculitis associted with other primary

diseases, infection, malignancy, diseases, infection, malignancy, rheumatic diseaserheumatic disease

Pathophysiology and Pathophysiology and PathogenesisPathogenesis

Immunpathogenic mechanismsImmunpathogenic mechanisms Pathogenic immune complex formation and/or Pathogenic immune complex formation and/or

deposition:Hepatitis B PAN, Hepatitis C deposition:Hepatitis B PAN, Hepatitis C Essential mixed cryoglob.Essential mixed cryoglob.

Production of antineutrophilic cytoplasmic Production of antineutrophilic cytoplasmic antibodies: Wegenerantibodies: Wegener´́s, Churg-Strauss, s, Churg-Strauss, Microsc. polyang.Microsc. polyang.

Pathogenic T lymphocyte responses and Pathogenic T lymphocyte responses and granuloma formation:Giant cell, Takayasugranuloma formation:Giant cell, Takayasu´́s, s, Wegener, Churg-StraussWegener, Churg-Strauss

Approach to the patient: Approach to the patient: VasculitisVasculitis

Unexplained systemic illnessUnexplained systemic illness Angiogram of organsAngiogram of organs Definitive diagnosis→biopsy of involved Definitive diagnosis→biopsy of involved

tissuetissue

WegenerWegener´́s s granulomatosisgranulomatosis

Incidence and PrevalenceIncidence and Prevalence Prevalence: 3 per 100.000Prevalence: 3 per 100.000 Age of onset: 40 yearsAge of onset: 40 years Primary vasculitis syndrome→ damage of vesselsPrimary vasculitis syndrome→ damage of vessels Immunopathogenic mechanismsImmunopathogenic mechanisms ANCA= antineutrophil cytoplasmic antibodyANCA= antineutrophil cytoplasmic antibody c-ANCA= cytoplasmic ANCA c-ANCA= cytoplasmic ANCA (diffuse, granular cytoplasmic staining by (diffuse, granular cytoplasmic staining by

immunofluorescence microscopy)immunofluorescence microscopy) Detectable antibodies to proteinase-3Detectable antibodies to proteinase-3 Granuloma formationGranuloma formation

Pathology and Pathology and pathogenesispathogenesis

Necrotizing vasculitis of small arteries and Necrotizing vasculitis of small arteries and veins + granuloma formationveins + granuloma formation

Lung: multiple, bilateral, nodular cavitary Lung: multiple, bilateral, nodular cavitary infiltratesinfiltrates

Biopsy: necrotizing granulomatous vasculitisBiopsy: necrotizing granulomatous vasculitis Upper airway lasions: sinuses, nasopharynxUpper airway lasions: sinuses, nasopharynx Kidney: rapidly progressive crescentic Kidney: rapidly progressive crescentic

glomerulonephritisglomerulonephritis

Clinical manifestationsClinical manifestations Upper airways 95%Upper airways 95% Purulent or bloody nasal dischargePurulent or bloody nasal discharge Nasal septal perforationNasal septal perforation Saddle nose deformitySaddle nose deformity Serous oitis media, hearing lossSerous oitis media, hearing loss Subglottic tracheal stenosis→severe airway obstructionSubglottic tracheal stenosis→severe airway obstruction Pulmonary involvement:hemoptysis, dyspnea 85-90%Pulmonary involvement:hemoptysis, dyspnea 85-90% Eye: scleritis, conjunctivitis, retroorbital mass laesionEye: scleritis, conjunctivitis, retroorbital mass laesion Skin: palpable purpura, papules, vesicles, subcutaneous nodulesSkin: palpable purpura, papules, vesicles, subcutaneous nodules Heart: pericarditis, coronary vasculitisHeart: pericarditis, coronary vasculitis CNS: mononeuritis multiplex, cerebral vasculitisCNS: mononeuritis multiplex, cerebral vasculitis Kidney disease: 77%, proteinuria, hematuria, red blood cell casts, Kidney disease: 77%, proteinuria, hematuria, red blood cell casts,

rapidly progressive renal failurerapidly progressive renal failure

Laboratory findingsLaboratory findings ESR↑ESR↑ Mild anemia, leukocytosis, Mild anemia, leukocytosis,

thrombocytosisthrombocytosis 90% positive antiproteinase-3 c-ANCA90% positive antiproteinase-3 c-ANCA

Diagnosis of WGDiagnosis of WG Tissue biopsy: necrotizing granulomatous Tissue biopsy: necrotizing granulomatous

vasculitisvasculitis c-ANCA positivityc-ANCA positivity

Treatment of WGTreatment of WG Cyclophosphamide induction for severe Cyclophosphamide induction for severe

disease: 2 mg/kg per day orally + steroidsdisease: 2 mg/kg per day orally + steroids Cyclophosphamide for 1 year following the Cyclophosphamide for 1 year following the

induction of complete remissioninduction of complete remission Prednisone 1 mg/kg per dayPrednisone 1 mg/kg per day Improvement: 90%Improvement: 90% Complete remissions: 75%Complete remissions: 75% Later relapsesLater relapses Remission maintenance: Azathioprine, Remission maintenance: Azathioprine,

Methotrexate 2 years past remissionMethotrexate 2 years past remission

Treatment of WG 2Treatment of WG 2 Mycophenolate mofetil 1000 mg twice a Mycophenolate mofetil 1000 mg twice a

dayday Rituximab (anti-CD20)Rituximab (anti-CD20) Trimethoprim-sulfamethoxazoleTrimethoprim-sulfamethoxazole

Churg-Strauss syndromeChurg-Strauss syndrome

DefinitionDefinition Allergic angiitis and granulomatosisAllergic angiitis and granulomatosis Asthma, peripheral and tissue Asthma, peripheral and tissue

eosinophilia, extravascular granuloma eosinophilia, extravascular granuloma formation, vasculitis of multiple organsformation, vasculitis of multiple organs

Incidence and PrevalenceIncidence and Prevalence 1-3 cases per million1-3 cases per million Onset: 48 yearsOnset: 48 years

Pathology and Pathology and PathogenesisPathogenesis

Necrotizing vasculitisNecrotizing vasculitis Small and medium-sized muscular Small and medium-sized muscular

erteries, capillaries, veins, and venuleserteries, capillaries, veins, and venules Granuloma formationGranuloma formation Infiltration of the tissues with eosinophilsInfiltration of the tissues with eosinophils Lung, skin, heart, kidney. Lung, skin, heart, kidney.

Peripheralnervous system, GIPeripheralnervous system, GI

Clinical and Laboratory Clinical and Laboratory ManifesttionsManifesttions

Asthma, pulmonary infiltratesAsthma, pulmonary infiltrates Mononeuritis multiplexMononeuritis multiplex Allergic rhinitis and sinusitisAllergic rhinitis and sinusitis Skin lesions: purpura, subcutaneous nodulesSkin lesions: purpura, subcutaneous nodules EosinophiliaEosinophilia ESR↑ESR↑ p-ANCA = perinuclear ANCA p-ANCA = perinuclear ANCA

(antimyeloperoxidase)(antimyeloperoxidase)

DiagnosisDiagnosis AsthmaAsthma Peripheral blood eosinophiliaPeripheral blood eosinophilia BiopsyBiopsy

TreatmentTreatment SteroidsSteroids CyclophosphamideCyclophosphamide Survival rate:72%Survival rate:72%

Polyarteritis nodosaPolyarteritis nodosa

DefinitionDefinition Multisystem, necrotizing vasculitisMultisystem, necrotizing vasculitis Small and medium-sized muscular Small and medium-sized muscular

arteriesarteries Renal and visceral arteriesRenal and visceral arteries

Incidence and PrevalenceIncidence and Prevalence Very uncommon diseaseVery uncommon disease

Pathology and Pathology and PathogenesisPathogenesis

Segmental lesionsSegmental lesions Bifurcations and branching of arteriesBifurcations and branching of arteries Aneurysmal dilatations up to 1 cm in sizeAneurysmal dilatations up to 1 cm in size Kidney: arteritis without glomerulonephritisKidney: arteritis without glomerulonephritis Hepatitis B antigenemia: 10-30%Hepatitis B antigenemia: 10-30% Circulating immune complexes composed Circulating immune complexes composed

of hepatitis B antigenof hepatitis B antigen

Clinical manifestationsClinical manifestations Fever, weight lossFever, weight loss Kidney→renal failure, hypertensionKidney→renal failure, hypertension Joint→arthritis, arthralgia, myalgiaJoint→arthritis, arthralgia, myalgia Peripheral neuropathy, mononeuritis multiplexPeripheral neuropathy, mononeuritis multiplex GI→abdominal pain, bleeding, bowel infarction and GI→abdominal pain, bleeding, bowel infarction and

perforation, liver infarction, pancreatic infarctionperforation, liver infarction, pancreatic infarction Skin→purpra, nodules, cutaneous infarcts, livedo reticularisSkin→purpra, nodules, cutaneous infarcts, livedo reticularis Heart→congestive heart failure, myocardial infarction, Heart→congestive heart failure, myocardial infarction,

pericardiispericardiis Testicular and ovarian painTesticular and ovarian pain CNS→cerebral vascular accident, seizure, altered mental CNS→cerebral vascular accident, seizure, altered mental

statusstatus

Laboratory testsLaboratory tests Leukocyte count↑Leukocyte count↑ ESR↑ESR↑ Anemia of chronic diseaseAnemia of chronic disease HypergammaglobulinemiaHypergammaglobulinemia HBsAg pozitivity 30%HBsAg pozitivity 30%

DiagnosisDiagnosis Vasculitis on biopsy material of involved Vasculitis on biopsy material of involved

organsorgans Angiography→aneurysms of small and Angiography→aneurysms of small and

medium-sized arteriesmedium-sized arteries

TreatmentTreatment SteroidSteroid CyclophosphamideCyclophosphamide PAN + Hepatitis B virus pozitivity: PAN + Hepatitis B virus pozitivity:

Antiviral drugs+ steroid+plasma Antiviral drugs+ steroid+plasma exchangeexchange

Microscopic polyangitisMicroscopic polyangitis Glomerulonephritis→renal failureGlomerulonephritis→renal failure Pulmonary capillaritis→hemoptysisPulmonary capillaritis→hemoptysis Mononeuritis multiplexMononeuritis multiplex GI vasculitisGI vasculitis Cutaneous vasculitisCutaneous vasculitis Age of onset: 57 yearsAge of onset: 57 years pANCA positivity 75%pANCA positivity 75%

Diagnosis and TreatmentDiagnosis and Treatment Kidney,lung: histologic evidence of Kidney,lung: histologic evidence of

vasculitisvasculitis Steroid +CyclophosphamideSteroid +Cyclophosphamide

Giant cell arteritis and Giant cell arteritis and Polymyalgia rheumaticaPolymyalgia rheumatica

DefinitionDefinition Temporal arteritis or Cranial arteritisTemporal arteritis or Cranial arteritis Inflammationof medium- and large-sized Inflammationof medium- and large-sized

arteriesarteries Temporal arteryTemporal artery Aorta and its main branchesAorta and its main branches Polymyalgia rheumatica: pain in the muscles Polymyalgia rheumatica: pain in the muscles

of the neck, shouldersm lower backof the neck, shouldersm lower back >>50 years50 years

Clinical and Laboratory Clinical and Laboratory ManifestationsManifestations

Fever,anemiaFever,anemia ESR↑ESR↑ HeadacheHeadache Temporal artery→tender, thickened, nodularTemporal artery→tender, thickened, nodular Ischemic optic neuropathy→visual Ischemic optic neuropathy→visual

loss→blindnessloss→blindness Increased risk of aortic aneurysm→ dissectionIncreased risk of aortic aneurysm→ dissection

DiagnosisDiagnosis Biopsy of the temporal arteryBiopsy of the temporal artery Giant cell arteritisGiant cell arteritis

TreatmentTreatment Steroid: Prednisone40-60 mg/day 1 Steroid: Prednisone40-60 mg/day 1

monthmonth Treatment for≥ 2 yearsTreatment for≥ 2 years ESR↓ESR↓ Polymyalgia rheumatica: Prednisone 10-Polymyalgia rheumatica: Prednisone 10-

20 mg/day20 mg/day ESR↓ESR↓

TakayasuTakayasu´́s arteritiss arteritis Inflammatory and stenotic disease of Inflammatory and stenotic disease of

medium- and large-sized arteriesmedium- and large-sized arteries Aortic arch and its branchesAortic arch and its branches =Aortic arch syndrome=Aortic arch syndrome Incidence: 1-2 cases/million/yearIncidence: 1-2 cases/million/year AngiographyAngiography

Frequency of Frequency of angiographic angiographic abnormalitiesabnormalities

Subclavian: 93%Subclavian: 93% Common carotid: 58%Common carotid: 58% Abdominal aorta: 47%Abdominal aorta: 47% Aortic arch: 35%Aortic arch: 35% Vertebral: 35%Vertebral: 35% Pulmonary: 10-40%Pulmonary: 10-40% Coronary Coronary << 10% 10%

Clinical manifestetionsClinical manifestetions Panarteritis with inflammatory Panarteritis with inflammatory

mononuclear cell infiltratesmononuclear cell infiltrates Narrowing of the lumenNarrowing of the lumen Pulses absentPulses absent ESR↑, anemia, gammaglobulin↑ESR↑, anemia, gammaglobulin↑

DiagnosisDiagnosis Young womanYoung woman Decrease or absence ofperipheral pulsesDecrease or absence ofperipheral pulses Discrepancies in blood pressureDiscrepancies in blood pressure Arterial bruitsArterial bruits Arteriography→irregular vessel walls, Arteriography→irregular vessel walls,

stenosis, poststenotic dilatation, stenosis, poststenotic dilatation, aneurysm formation, occlusion, evidence aneurysm formation, occlusion, evidence of increased collateral circulationof increased collateral circulation

TreatmentTreatment Steroid: prednisone 40-60 mg/daySteroid: prednisone 40-60 mg/day Methotrexate 25 mg/weekMethotrexate 25 mg/week Surgical correction of stenosed arteriesSurgical correction of stenosed arteries

Henoch-Schönlein Henoch-Schönlein purpurapurpura

Anaphylactoid purpuraAnaphylactoid purpura Palpable purpura over the buttocks and lower Palpable purpura over the buttocks and lower

extremitiesextremities ArthralgiasArthralgias GI signs→colicky abdominal pain, GI signs→colicky abdominal pain,

melena/hematochesiamelena/hematochesia Glomerulonephritis→proteinuria, microscopic Glomerulonephritis→proteinuria, microscopic

hematuria, red blood cell casts hematuria, red blood cell casts Small-vessel vasculitisSmall-vessel vasculitis Children 4-7 yearsChildren 4-7 years Immune-complex depositionImmune-complex deposition Serum IgA↑Serum IgA↑

DiagnosisDiagnosis Clinical symptomsClinical symptoms Skin biopsy→ leukocytoclastic vasculitisSkin biopsy→ leukocytoclastic vasculitis

TreatmentTreatment Do not require therapyDo not require therapy Steroids: Prednisone 1 mg/kg/daySteroids: Prednisone 1 mg/kg/day

Idiopathic cutaneous Idiopathic cutaneous vasculitisvasculitis

=Hypersensitivity vasculitis=Hypersensitivity vasculitis =Cutaneous leukocytoclastic vasculitis=Cutaneous leukocytoclastic vasculitis Dermis, small vesselsDermis, small vessels Only skin involvement→palpable purpura, Only skin involvement→palpable purpura,

chronic urticariachronic urticaria Diagnosis: biopsy→vasculitisDiagnosis: biopsy→vasculitis Etiology: drug, infection, underlying diseaseEtiology: drug, infection, underlying disease Treatment:microbe→antimicrobal therapy, Treatment:microbe→antimicrobal therapy,

steroidssteroids

Essential mixed Essential mixed cryoglobulinemiacryoglobulinemia

Cryoglobulins: cold-precipitable Cryoglobulins: cold-precipitable monoclonal or polyclonal monoclonal or polyclonal immunoglobulinsimmunoglobulins

Cutaneous vasculitis, palpable purpura, Cutaneous vasculitis, palpable purpura, arthralgias, glomerulonephritisarthralgias, glomerulonephritis

Hepatitis C infectionHepatitis C infection Treatment:IFN-Treatment:IFN-αα, Ribavirin, Ribavirin

BehcetBehcet´́s syndromes syndrome Recurrent, painful aphthous oral Recurrent, painful aphthous oral

ulcerations in the oral cacityulcerations in the oral cacity Recurrent genital ulcersRecurrent genital ulcers IritisIritis Cutaneous lesionsCutaneous lesions Treatment: topical steroids, PrednisoneTreatment: topical steroids, Prednisone

Isolated vasculitis of the Isolated vasculitis of the CNSCNS

Severe headache, focal neurologic Severe headache, focal neurologic defectsdefects

Abnormal MRI of the brainAbnormal MRI of the brain Abnormal liquorAbnormal liquor Abnormal cerebral angiogram→vasculitisAbnormal cerebral angiogram→vasculitis Brain biopsyBrain biopsy Treatment:Prednisone+CyclophosphamidTreatment:Prednisone+Cyclophosphamid

ee

Kawasaki diseaseKawasaki disease =Mucocutaneous lymph node syndrome=Mucocutaneous lymph node syndrome Nonsuppurative cervical adenitisNonsuppurative cervical adenitis Children Children >> 2 years 2 years Coronary artery aneurysms 25%Coronary artery aneurysms 25% Treatment:IVIG+ AspirinTreatment:IVIG+ Aspirin

RaynaudRaynaud´́s Phenomenons Phenomenon Episodic vasoconstriction inthe fingers and toesEpisodic vasoconstriction inthe fingers and toes Tip of the nose and earlobesTip of the nose and earlobes Cold exposureCold exposure pallor→cyanosis→erythema rewarming of the pallor→cyanosis→erythema rewarming of the

fingers, vasoconstriction→ischemia→reperfusionfingers, vasoconstriction→ischemia→reperfusion Normal population: 3-5%, womenNormal population: 3-5%, women Primary and/or secondaryPrimary and/or secondary Nailbed cutaneous capillaries viewed Nailbed cutaneous capillaries viewed

stereoscopic microscopestereoscopic microscope

TreatmentTreatment Dress warmly, calcium channel blockers, Dress warmly, calcium channel blockers,

ARBs (angiotensin II receptor blockers) ARBs (angiotensin II receptor blockers) Losartan, iv. prostaglandins, low-dose Losartan, iv. prostaglandins, low-dose aspirinaspirin