the vasculitis syndromes
DESCRIPTION
Definition Inflammation and damage of blood vessels Single organ→ skin Several organ systems Primary Secondary Heterogeneity OverlapTRANSCRIPT
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