Respiratorymanifestationof

SystemicVasculitis

PekingUnionMedicalCollege（TsinghuaUniversityhealthsciencecenter）PekingUnionMedicalCollegeHospitalConceptSystemicVasculitis(SV)isakindofinflammatorydiseasewithvascularinflammationandnecrosisasthemainpathologicfeature.Thetype,size,siteandpathologicfeatureoflesionvesselsaredifferent,

thustheclinicalmanifestationaremultiformity.Although

SV

usuallyinducedysfunctionofmultiorgan,sometimesitmaybelocalizedinaspecificorgan.Themain

damagesitesareskin,kidney,lung,andnevoussystem,andsoon.

TheclinicalrepresentationsofSVarecomplicatedanddiverse,mostofwhicharedifficulttodiagnosis.

ChapelHillConferenceRecommendationGreat-vasculitis

Takayasu

arteritisGiantcellartetitis/TemporalarteritisIsolatedCNSAngiitis

CogansSyndromeMedium-vesselsarteritis

Polyarteritis

nodosaKawasakidiseaseSmall-vesselartetitis

Wegener's

granulomatosis

Churg-StraussSyndromeMicroscopicpolyarteritis

Cutaneous

loukocytoclastic

angiitis

Henoch-Schonlein

purpuraPrimarycryoglobulinemia

vasculitis

Primaryvasculitis

Effectsongreat,mediumandsmallvessels

Takayasu

arteritisGiantcellartetitis/TemporalarteritisIsolatedCNSAngiitis

CogansSyndrome

Effectonmediumandsmallvessels

Polyarteritis

nodosaandCutanenous

polyarteritis

nodosa

Wegener's

granulomatosis

Churg-StraussSyndromeKawasakidiseaseBurger’sdisease

Effectonsmallvessels

Cutaneous

loukocytoclastic

angiitis

Henoch-Schonlein

purpuraSerumdisease

Hypocomplementemia

urticarial

vasculitisPrimarymixedtypecryoglobulinemia

Degossyndromes

BehcetdiseaseSecondary

vasculitisInfection-associatedvasculitisConnectivetissuediseaseassociatedvasculitisDrug-associatedvasculitisCancer-associatedvasculitis

OrgantransplantationassociatedvasculitisSystemicdiseaseassociatedvasculitisClassificationofCayRMandBallVRelativeConstituent

Ratio

ofVasculitis

Giantcellartetitisl:21.4%Microscopicpolyarteritis

（includingclassicalPANandMPA）:11.8%Allergicpurpura:9.3％Wegener's

granulomatosisandloukocytoclastic

angiitis:8.5％respectivelyPolyarteritis:6.3％Kawasakidesease:5.2％Churg-Straussvasculitis：2.0％Others（includingothertypesandunclassifiedtypesofvasculitis）：27.0％ClinicalManifestationGeneralSign:fever,weightdescent,debilitation,weary,fastidium.Muscleskeleton:myosalgia,arthrodynia,arthrositis,anginacrurisofupperjaworextremities.Skin:livedo

reticularis,purpura,erythemanodosa,cnidosis.Nervoussystem:headache,stroke,visionalteration,peripheralinflammatetionofsingleormulti-nerves.Respiratorysystem:paranasalsinusitis,haemoptysis,asthma,airsacculitis,intrapulmonarynodus,

pulmonaryinfiltrationKindey：renalhypertension,albuminuria,abnormalofurinarysediment,necrotizingglomerulonephritis.Digestivesystem:diarrhea,stomachache,alimentarytracthemorrhage,liverenzymehighten.Abnormalchemicalexamination:CrandBUNheighteninserum,anaemia,WBCheighten,thrombocytopenia,hypocomplementemia,hypsoglobulinmia-γ,ESRincrease，CRP

heighten.ANCApositive.anti-endothelialcellantibodypositive.ClinicalManifestation

ClinicalManifestationTherearenospecificclinicalmanifestationsofSystemic

Vasculitis.Therepresetationmentionedmaybe

checkedonotherdiseasessuchasinfectionand

tumordiseases.

Whenthereareevidencestoshow

multisystem

dysfunctionorabnormalindexsofacuteinflammatorystage,

andwecannotexplainby

commondiseases,weshouldsuspecttheoccurrenceofvasculitis，andthentakemoreexaminationsforfinaldiagnosis.Birminghamvasculitisactivityscore(BVAS)Birminghamvasculitisactivityscore(BVAS)

The

new

sign

presentoraggravate

causedbyvasculitisinprior4weeks:Systemicmanifestation3(

maxpoint)Skinmanifestation6(maxpoint)Mucousmembranes/eye6(maxpoint)

Ear,nose,throat 6(maxpoint)Chest 6(maxpoint)

Cardiovascular 6(maxpoint)Abdomen 9(maxpoint)

Kidney 12(maxpoint)Nervoussystem 9(maxpoint)

Illustration:1．Therearethemaxpointineverysystem,themaxpoint

is63point.2．Thepointabove15maybeconsideredasdiseaseactivity.3．LoqmaniRA,BaconPA,mootsRJ,etal.Birminghamvasculitisactivityscore(BVAS)insystemicnecrotizingvasculitis.QJMed,1994,87:671-8.

Chest

(Themaximumscoresoftotal:6points)

None

0Dyspnea/Gasp 2Pulmonarynodus/fibrosis 2Pleuraleffusion/Pleuritis

4Inflammatoryeffusion 4Haemoptysis/Pneumorrhagia

6Severehaemoptysis

6ANCA-associated

vasculitisWegener's

granulomatosis(WG)Churg-Strausssyndrome(CSS)Microscopicpolyangiitis(MPA)ANCA-associatedvasculitisTherearemany

similaritiesbetweenWegener's

granulomatosis(WG),Microscopicpolyangiitis(MPA)andChurg-Strausssyndrome(CSS)inpathology,clinicalandlaboratory

features,thustheyaresorted

into

onetype.ANCA-associatedvasculitisThehistologicalfeatureofthesediseasesisthedamageofthesmallvessels(smallveins,capillaryandsmallarteriole);Theyhavethesimilarcomplications—glomerulumdamage(suchasfocalnecrosis,crescentformation,no/fewglobulindeposition；Thesimilarclinicalmanifestation,suchaspneumonephros

syndrome.ThemostimportantthingisANCApositiveANCAPR3-ANCAandMPO-ANCAcanbedetectedinsomespecificdieases,suchas

threesmallvasculitisandkindeyvasculitis(Idiopatheticnecroticcrescentic

glom-erulonephritis).SensitivityofANCAforthesediseasesisinrangeof50%～90%.TheresultofalargescalemulticentretestinEuropeshowedthatmany

patientswithprimarysmallvasculitis

were

ANCAnegative,thusanegativeresultcannotexcludethediagonsisofdoubtfulvasculitis.ANCAexaminationisvaluable

underthe

basisoftheCompr-ehensiveanalysis

ofclinicalfindings.

PathologyVasculitiscanbeinvolvedinall

typesofvessels,itcanbeclassifiedintofourtypesbasedontheclassificationof

inflitratecellandpathologicfeatures:Leukocytoclastic

vasculitis；Lympholeukocyte

granuloma

artetitis；Giantcellvasculitis；Necroticvasculitis.Theselesionsof

angiostegnosisandneoplasia

ofvesselwallcaninduce

ischemiaoflocaltissue.VasculiticLungInvolvementThecommonvasculitis

Wegener's

granulomatosis(WG)Churg-Strausssyndrome(CSS)Microscopicpolyangiitis(MPA)Takayasu

arteritis(TA)BehcetDisease(BD)Wegener's

Granulomatosis(WG)LesionsofUpperrespiratorytractwith

WGsymptoms

of

LowerrespiratorytractOneofthebasic

characteristics；Emergeatonset

—50%；Emerge

incourseofdisease—85%；Cough,haemoptysis,pleuritis,shortbreath;

Lungshadow

associatedwithcavity:variable;Diffusealveolarhemorrhage(DAH)israre:diffuse

ground-glass

lucency

reduceMortalityincreasewhenaccompaniedbypulmonaryinfection.

PulmomayInvolvementsAlveolarhemorrhagePulmonaryvasculitisPathologiccharacteristicsof

WG

Theclassical

inflammatorylesions:necrosis,

guanulomaandvasculitis.Sizeofspeciman,entirety

of

sliceandintegrityoffilmreadingaffectthefinaldiagnosis.PathologicchangesofparanasalsinusandaccessorynasalsinuswithWGPathologicspecimensofheadandneck

are

few(mostlycomefromparanasalsinusandaccessorynasalsinus)，soitisdifficulttodescribealloftheWG’sPathologiccharacteristics.TheoverlapofVasculitis,necrosisandgranulomainflammationcanbefoundinrangeof1/3-1/2specimen.Vasculitisandnecrosiscanbefoundin1/5biopsyspecimensimultaneously.Vasculitisandgranulomainflammationcanbefoundin1/5biopsyspecimensimultaneously.PathologicchangesofparanasalsinusandaccessorynasalsinuswithWGThemostimportantthingisthattheconfirmedtriadcanbefoundinapproximately

3%～16%biospyspecimen.Thusbiospyofheadandneck

usually

showthecharacteristicsofWGwithout

specificity.Beawareofthelack,wecancorrectlyexplaintheresultofpatients’

headandneck

biospy

specimen.PathologiccharacteristicsofpulmonarywithWGThepathologicdiagnosisofpulmonarydiseasemaybeaffectedbythesizeofbiospyspecimen.WGcan’tdiagnosedbyBrochial

biospy

(lessthan7%).TherearesimultaneousSituationof

necrosis,guanlomaandvasculitisinabout90%oflungbiospyspecimen.The

examinationofbronchoscopyandbronchialbiopsycanbeusedtoexcludethediagnosisofbacteria,Mycoandfungousinfection，whichmaydisplaythesimilarsignswithWGorWG

aggravation.

PathologiccharacteristicsofpulmonarywithWGCapillaritiscanbefoundinabout35%～40%surgicalbiospyspecimen.Aclinicalresearchindicatedthat

capillaritisweredisplayedinallofthe11diffusealveolarhemorrhagepatients.Capillatitishasnodiagnosisspecificity.Capillatitiscanbefoundinsystemiclupuserythematosus,immunocomplexassociatedvasculitis,dermatomyositis,rheumatoidarthritis，allergicpurpuraorbronchopneumonitis.Churg-Strausssyndrome(CSS)

OverviewItwasfirstreportedbyChurgandStraussin1951.ChurgJ,StraussL.Allergicgranulomalusis，allergicangiitisandperiarteritis

nodusa.AmJPathol1951.17,277-301．OverviewPrimaryandsystemicsmallvasculitis.Involvesmallarteryandsmallveinmainly.Characterized

bybronchialasthma,eosinophiliaandcrenotic

granuloma

vasculitis.Namedasallergicgranulomatosis

vasculitis.ClinicalmanifestationComplex

MaleusuallySusceptibleage:(24-54)yrStagingVasculitisprotophase:allergicrhinitis(28yr),asthma(35yr)Vasculitisperiod

:

classicalpathologicchangeVasculitisanaphase:asthma,allergicrhinitis,peripherialnervediseaseHistologic

characteristicsHistologicbiopsy:lungbiopsy,nervemusclebiopsy,skinbiopsy

(1)Acidophiletissueinfiltration

(2)Necroticvasculitis

(3)Extravasculargranulomaformation

Be

limitedin

acertaintissueorwidespead.Variouskindsofpathologicalchanges

cannotalwaysemergesimultaneously.Multisystemmanifestation:lungFever,cough,dyspneaChestX-rayindicate:migratorypatchingshadowinsingleortwosidesoflung,transparencyreductioninouterzoneoflung,pleuraleffussionLotsofacidophilecellsinBALFandpleuralfluid:aRespiratorysystem（1）AllergicrhinitisItmaybefoundinabout70%patientsastheoriginalrepressentation.Itsmainmanifestationincludedsruffiness,purulentorhaemicnasaldischarge,accompaniedcommonlybyrhinopolypusandparanasalsinusitis.（2）Asthma80-100%ofpatients.Inearlyperiodusually.Ininitialstageconditionwasnotsevere,whichwascharacterizedbyshortexacerbationandlonginterval.Inlateperiod,conditionaggravatedgradually,asthmaexacerbatedfrequently,responddullytoconventionalantiasthmaticdrug.Thereisnorelationshipabouttheseveritybetweenasthmaandsystemicdamage.Asthmacouldberelievedsuddenlyastheappearanceofvasculitisinsomepatients.Sometimes,itmayaggravategradually,endedasrefractoryasthma.（3）PathologicalchangeinlungCSSdisplayedaseosinophilicpneumoniamainly,whichmaybefoundattheprotophaseorvasculitis

paseinabout72-93%ofMPApatients.ThemainX-raymanifestationisinvasivechangeswhitoutspecificity,whichincludednodosityorpatchingshallow,withoutconcinnousborderline,asystematic,withoutspecificsite,formcavityseldomly,variable.Chroniceosinophilegranulocytecouldbefoundintheseverecases.（3）PathologicalchangeinlungSomeonecouldexpressintra-alveolarhemorrhage:haemoptysis,dyspnea,hypoxmiaandanaemia,and—asystematicmassiveshallowinpulmonaryX-ray.About27%ofpatientshadpleuraleffussionfor.ClinicalmanifestationofCSSDomesticliteraturesOverseasliteraturesNumber(n)11138Sex(M/F)Ratio2.71.09Meanage(yr)38.938Percentage(%)

Fever100Asthma72.7100Infiltrationinlung36.49Allergicrhinitisorparanosal

sinusitis36.474Multitudemononeuritis

81.864

Skindamage90.9

Purpura

36.446

Nodus

18.233Gastrointestinalchange83.362Heartimpair66.752Kidneyimpair63.642DiagnosisMaincreteria：ClinicalmanifestationPeripheralacidocytosisHistology

Biospy——GoldstandardofdiagnosisforCSSCSSshouldbeconsideredwhenmultisystemrepresentationemergeinpatientswithlonghistoryofasthma:uncavitaryinfiltration,subcutaneousnodule,peripheralneuropathy,abdominalangina,myocardiopathy,eosinophilsofperipheralbloodmorethan1.5X109/LorANCApositive.

Microscopicpolyangiitis(MPA)

Necroticvasculitis(capillary,smallvein,srterioleandartery).Noorfewsituimmunitydeposition..Therearemiddleorvesselassociatednecroticarteritisinsomepatients.Necroticglomerulonephritisandpulmonarycapillaryarecommon.MicroscopicpolyangiitispANCA,MPO-ANCA*Arthritis&Rheum,1994,37:187-192Necroticglomerulonephritiswithoutimmunitydesposition.WLG03/02TheimpactofMPAonpulmomayPulmonaryalveolicapillaritis:50%oflunginjuryDiffusealveolarhemorrhage:12%-29%DyspneaordeathinducedbymassivepulmonaryhemorrhagePulmonaryinterstitialfibrosisbaseondiffusealveolarhemorrhageinsomepatientsTheGeneralconditionsof16patientswithMPA

PUMCHn=16

SexM：F=10:6=1.67：1Age(years)14-69(52.5±15.3)Longth(months)6-32Diagnosisbase

Renalbiopsy7(43.8%)Lungbiopsy1(6.25%)Clinical&Lab8(50%)ANCA(+) 15(93.75%)Anti-PR3ANCA*（+）3(18.75%)Anti-MPOANCA**（+）12(75%)

Table2Clinicalmanifestationof16MPApatientsandthecomparisonwithliteraturesClinicalmanifestationNincidenceIncidenceinliteratures%ClinicalmanifestationNincidenceIncidenceinliterature

Fever1610050-72alimentarytracthemorrhage85021-32Wasting956.347-79arthralgia637.528-65Kidney16100100myosalgia318.7576-79RPGN1168.7571-89Eyedamage425

CGN531.25

Hearingdecrease42530Skin531.2540-44pharyngalgia318.7530Congestion212.5

decrease212.5

15-30

Purpura212.25

NS85028Nodus16.3

CN212.570-85Cadiovascu531.2522-38

PN

637.512-23hypertension318.75

APS16.3individualcase

Fluidify

16.3

lungdamage

127550Heartfailure16.3

ReferencetoKelly’sTextBookofRheumatology,6theditionTable3Clinicalandlaboratoryfeaturesof12MPApatientswithlunginjuryNDiagnosis(m)

primarysignoflungCXR/CTHRCTLungfunction

BALFANCApc14Cough,shortbreathpulmonaryinterstitialfibrosisDiffusionpleuralfluidRestricventilation/diffusiondisorderHemosiderincells(+)1：640（-）25Cough,expectoration,shortbreathnormalLocalpleuralfluidRestricventilation/diffusiondisorderNocheck（-）1：8035Cough,expectoration,pulmonaryinfectionLocalpleuralfluidRestricventilation/diffusiondisorderNocheck1：160（-）43Cough,shortbreathSuffusionpulmonaryinterstitialfibrosisDiffusionpleuralfluidRestricventilation/diffusiondisorderNocheck1：640（-）52Cough,shortbreathSuffusionpulmonaryinterstitialfibrosisDiffusionpleuralfluidRestricventilation/diffusiondisorderT4/T8=0.51：640（-）62Cough,expectoration,shortbreathSuffusionpulmonaryinterstitialfibrosisDiffusionpleuralfluidMixventilation/siffusiondisorderNocheck1：640（-）74Cough,expectoration,shortbreathpulmonaryinfectionDiffusionpleuralfluidRestricventilation/diffusiondisorderNocheck1：64（-）828Cough,expectorationPneumoniapneumoniaObstructventilation/diffusiondisorderNocheck1：160（-）98Hemoptysis,chestpainPneumonorrhagia

Pneumonorrhagia

Norma;Nocheck1：32（-）103Cough,expectoration,hemoptysisPneumonorrhagi

Pneumonorrhagia

NormalNocheck1：64（-）113Chestpain,shortbreathPleuralfluidPleural

fluidNormalNocheck1：160（-）127Cough,chestpainPleuralfluidPleural

fluidNormalNocheck1：64（-）NocheckOriginalpulmonaryrepresentationandlaboratoryexaminationof12MPApatientswithlungdamaged(table3):OnlyHaemoptysis:2DiagnosticHRCTexamforpulmonaryinterstitialfibrosispatients:3/7Coughastheoriginalsigninpulmonaryinterstitialfibrosis:6/7MisdiagnosisasIPF:3Lungfunctionexamination:restrictventilationdisorder——6/7,mixventilationdisorder——1/7,allwithdiffusiondisorder.

HaemosiderincellsinBALF:1(haemoptysisinthelatestge)c-ANCA(+):1/12,p-ANCA(+):11/12Hint

LiteraturesreportedthathaemoptysisisthecommonsignoflunginjuryinMPA.1990,Nada：3cases1999,A.Becker-Meroketal：1case.PulmonaryinterstitialfibrosisinitiallymaybetheinitiatemanifestationofMPA.MPAmaybemisdiagnosedasIPF.ThesecasessuggestedthatILDmaybetheimportantrepresentationinearlyperiodofMPA.**WeshouldonguardagainstMPAfor‘IPF’diagnosis.HRCTandlungfunctionexaminationwereimportantfortheearlydiagnosisofpulmonaryinterstitialfibrosisinMPA.Thepresenceofpulmonaryalveolhemorrhage

meaneddeteriorateofMPA.Bronchoalveolar

lavagefluid(BALF)couldbeconsideredasthesimplemeasuretofindpulmonaryalveolhemorrhage.Takayasu

arteritis(TA)Somereportsfoundaccompaniedpulmonaryhypertensionin50%TApatientsandnotableclinicalrepresentation:haemoptysis,chestpain.Someresearchescertificatedpulmonarydamagebylungbiopsyorvasographyinpatientswithoutsignofpulmonarysymptoms.PulmonarymanifestationofTakayasu’s

arteritisTypeofpulmonaryartery:Therewereabout50%TApatientsaccompaniedpulmonaryarterydamage,whichcombinewithaortitisoften.Clinicalmanifestation:palpitation,shortbreath.,pulmonaryhypertensionatadvancedstage.systolicmurmuratpulmonaryvalvearea,P2accentuation.（一）Pulmonaryinfection:Upperrespiratorytractorpulmonaryinfectionattheearlierperiod.Samepatientshaveactivetrberculosis(22%;neckormediastinallymphnodeweresufferedmainly,vascularsystemwasrarelyinvaded.)PulmonaryvasculopathyisthemainpulmonaryrepresentationofTakayasu‘s

arteritis.Pulmonaryarterydamagecanbefoundin50%ofTApatients.Theotherfourtypesmayallcombinewithpulmonaryarterydamage.Theratioofpulmonaryarterydamageareequivalencybetweendifferenttypes.Itisseldomthatonlypulmonaryarterybedamaged.Therearesomecasereportsabroad.Themainarteriographysignispulmonaryarterystegnosis.Arteryocclusionisseldom.Pulmonaryhypertensionisanadvancedcomplicationwhichaccountsforabout?,mainlyaslightormediumdegree.Mostpatientscouldhavenopulmonarymanifestationatearlierperiod,andsomemayhaverecurrenthaemoptysis

repeatly.Lungfunction:TherenoreportonlungparenchymadamageinTA.Thedisorderoflungfunctioninsomepatientsmaybecausedbythepulmonaryarterystegnosisandbloodstreamdecrease.Commonventilationdysfunctionandrarediffusiondysfunctionwerecardiopulmonarydisorderafterdecreasedlong-termpulmonarybloodstreamandpulmonaryhypertension.191TApatientsinPekingUnionMedicalCollegeHospitalfrom1982to2007PAH：12（6.3%）pulmonaryarterydamageastheoriginalsign:7（58.3%）typeI＋IV:8(66.6%),typeII＋IV:2（16.7%）,typeIII＋IV,1/12:1（8.3%）typeIV:1（8.3%）1deadfordecreasedcardiacoutcomeafteropration.Otherpatientsimproved.PAHisaseverecomplicationofTAatadvancedstage,usuallycombinewitharteriesdamageofothersites.ClinicalanalysisofpulmonaryhypertensioninTALaiJin-zhi,XuDong,ZengXiao-fengChinarheumatologyjournalBehcetDisease(BD)

Bechet‘sdisease(BD)isasystemicdiseaseinvolvemultisystemsandmultiorgans,andvasculitisisitsbasicpathologicchange.

Clinicalmanifestationincluderecurentoralulcer,tunicauveitis,genitalsandarthtitis,multipleangiemphraxis,damagesinskin,digestivetractandnervesystem.ClinicalfeatureInvolveingreatorsmallarteriesandveins.Mainclinicalmanifestations:recurrentoralulcerandperineumulcer.Arthrodynia,erythema/pustulapapule,thrombophlebitisoflowerextremity,tunicauveitis,anddamagesofdigestive,cardiovescular,nervesystem,kindeyandpulmonary.Positiveneedlingtestinactivestage.IgGandcomplementdepositionininvolvedsites.

Pulmonaryimpaircanbefoundin10%ofpatients,whichdisplayasrecurrentpneumiaandhaemoptysis(deadlysometimes)repeatly.ClinicalanalysisofpulmonaryhypertensioninBDWeiHua,RuJin-li,HeJun-mei,WangLi,ZengXiao-fengFrom2000toNovember2006,therewere8(3.5%)BD-associatedPAHamong232BDpatientsinPekingUnionMedicalCollegeHospitalTTEexamination：among8cases,3aorticvalvulopathy,2pulmonaryvalvulopathy,2mitralis

valvulopathy,2tricuspiddisease,2rightatrialenlargementand/orrightventricularhypertrophy.SeverePAH（SPAP＞60mmHg）:50%Specialmanifestationofvasculitis

AneurysmTakayasu

Arteritis

Giantcellartetitis/TemporalarteritisPolyarteritis

nodosa（Typicalpolyarteritis

nodosa）BehcetDiseaseSpecialmanifestationofvasculitis

HaemoptysisTakayasu

ArteritisGiantcellartetitis/TemporalarteritisWegener'sgranulomatosisChurg-StraussSyndroneMicroscopicpolyangiitisBehcetDiseaseSpecialmanifestationofvasculitisMyocardialinfarctionTakayasu

ArteritisGiantcellarteritis/TemporalarteritisWegener’sGranulomatosisChurg-StraussSyndroneMicroscopicpolyangiitisBehcetDiseaseKawasakidiseaseSpecialmanifestationofvasculitisPulmonarycapillaritisandpulmonaryinterstitialfibrosis:Wegener’sGranulomatosisChurg-StraussSyndromeMicroscopicpolyangiitisDiagnosisWeshouldconsiderthediagnosisofvasculitis:MultisystemdamageProgressiveglomerularnephritisorserumCrandBNNincreaseVariableshadoworfixedshadow/cavityinlungMononeuritisorpolyneuritisFeverwithunknown