八制自身免疫

八制自身免疫第1頁/共77頁RheumaticfeverisanimmunologicalinflammatorydiseasefollowsinfectionwithcertainstrainsofgroupAstreptococcieasilyrecurwithoutprophylaxiscarditischoreamigratorypolyarthritissubcutaneousnodulespermanentvalvulardiseaseerythemamarginatum第2頁/共77頁

Epidemiology

incidence：22/100000

inChina

season：winterorspringage：5–15y第3頁/共77頁北京兒童醫(yī)院1477名風(fēng)濕熱住院患者年齡分布約90%患者為>7歲兒童第4頁/共77頁Etiology☆

anonsuppurativecomplicationofgroupAstreptococcalinfectionoftheupperrespiratorytract☆

occurs1-4weeksafterconvalescenceofinfection☆

individualpropensity☆

environmentalfactorslatitudealtitudehumiditynutritioncrowdingage第5頁/共77頁P(yáng)athogenesismolecularmimicryofbacterialantigenssimilaritybetweenbacterialandselfmoleculesasrecognizedbyimmunecellsleadingtoacross-reactwithtargetorgansinthebodycirculatingimmunecomplexes(CIC)

circulatingimmunecomplexesactivatethecomplementsystemleadingtotheinflammatorychangesGeneticpronenessHLA-B35、HLA-DR4第6頁/共77頁capsule（synovialmembranes）Cellwallprotein（myocardium,endocardium）Cellwallpolysaccharides（myocardium,endocardium）

cellmembraneprotein

（myocardium

、subthalamicnucleus、caudatenucleus）TheantigensofGroupAstreptococciandmolecularmimicry第7頁/共77頁

pathology

急性滲出期（acuteexudativeperiod）增生期（proliferativeperiod）硬化期(scleroticperiod)

1

month3~4months2~3monthsconnectivetissueedemas,effuse,anddegenerate,infiltratedwithinflammatorycells.

Aschoffbodyinmyocardium,muscle,endocardium,subcutaneoustissuecollagenfiberhyperplasiaandscartissueformationmitral>aortic>tricuspid>pulmonary第8頁/共77頁acuteexudativeperiodedemaanddegenerationofcollagenandexudation

inpericardiumpericardialeffusionfibrinouspericarditis第9頁/共77頁proliferativeperiod

Aschoffbodyinendocardium中心：fibrinoidnecrosisofcollagen

外周：lymphocytes,plasmacellsandAschoffgiantcellsAschoffgiantcelllargecellswithtwoormorepalenucleithathaveprominentnucleoli.

第10頁/共77頁scleroticperiodmitralvalveshowsthickeningdistortedcusps,adherentcommissureswithcalcificationandthrombusdeposition,fusionandshorteningofchordaetendinae.stenoticmitralvalveshowsfusionofcommissures,missuresarefused;cuspsareseverelythickened.Thevalveisbothincompetentandstenotic.第11頁/共77頁ClinicalManifestationMajorclinicalmanifestations:

carditis;polyarthritis;chorea;subcutancousnodules;erythemamarginatumOrdinarycomplaints:

fever/arthralgia

Durationofacuterheumaticfever:

≤6months第12頁/共77頁

rheumaticcarditisIncidence:

40~50%OneandonlypermanentdamageEndocarditisMyocarditisPericarditis

Congestiveheartfailureduringtheinitialepisode:

5%~10%Pancarditis第13頁/共77頁MyocarditisTachycardiadisproportionatetothefeverCongestiveheartfailureGalloprhythmSoftsystolicmurmurheardattheapexECGabnormalitis：arrhythmias;prolongationoftheP-Rinterval;atrioventricularblock(AVB)

Cardiomegalyonx-rayBeforetreatment

aftertreatment

第14頁/共77頁

EndocarditisMitralregurgitation:

ApicalsystolicmurmurattheapexRelativemitralstenosis:

Low-pitchedmid-diastolicrumbleAorticregurgitation:

Diastolicmurmurinthethirdcostaattheleftsideofthesternum第15頁/共77頁

PericarditisPrecordialpainPericardialeffusion

Africtionrub

pericardialtamponade

hypotension;muffledheartsounds;jugularvenousdistensionStrikingincreaseinheartsizeonX-rayEchocardiography:pericardialeffusion＞50ml第16頁/共77頁RheumaticarthritisIncidence:

50%~60%

Acutemigratorypolyarthritis

Largerjointsoftheextremitiesareaffected:

knee、ankle、elbow、wrist

Red,hot,swollen,exquisitelytender

andpainfulifmoved

asonejointrecovered,anotherjointmaybeinvolved

arthritislastslessthan1monthwithoutdeformity第17頁/共77頁ChoreaIncidence:3%~10%Female＞male;8~12

yeasoldSudden,aimless,irregularmovementsoftheextremitiesandfacialmusclesthatsubsideduringsleepandexaggeratedbyemotionsEmotionalinstability:nervousMuscleweaknessandataxia:

clumsy,stumble,handwritingorspeechdisorders第18頁/共77頁erythemamarginatum

Thecharacteristicrashesconsistofanevanescent,pink,erythematousmaculae,withaclearcenterandserpiginousoutline.Therashistransient,migratoryandnonpruritic,whichfoundprimarilyonthetrunkandproximalextremities.第19頁/共77頁subcutaneousnodules

Subcutaneousnodulesarepainlesssmallswellings

overbonyprominences,primarilyovertheextensortendonsofthehands,feet,elbows,scalp,scapulae,andvertebrae.Nodulestendtooccurincropsandmaypersistfordaystomonthsaftertheonsetofacuterheumaticfever.第20頁/共77頁OtherclinicalfeaturesVariablefeverTirednesspalenessPneumoniaNosebleedsweatingAbdominalangina第21頁/共77頁LaboratoryfindingsBloodroutinetest:WBC↑,mildanemiaAcutephasereactants：ESR↑,CRP↑IsolationofgroupAstreptococci(+)Serumantibodyagainstthespecificstrptococci:ASO↑,ASK↑,AH↑,anti-DNaseB↑Immunesystem:IgG↑,IgA↑,C3

↑ECG:P-Rinterval↑,seconddegreeAVBRoutineroentgenogramEchocardiography第22頁/共77頁

TheJonesCriteriaRevisedwithAdditionofWorldHealthOrganizationRecommendationsMajorCriteriaMinorCriteriaCarditisFeverPolyarthritis,migratoryArthralgiaErythemamarginatumincreasedacute-phasereactantsChoreaESR↑,CRP↑SubcutaneousnodulesProlongedP-Rinterval

PlusEvidenceofaprecedinggroupAstreptococcalinfection(culture,rapidantigen,antibodytitersrise/elevation,historyofscarletfever)★

twomajormanifestations+EvidenceofS.I(streptococcalinfection)★

onemajor＋twominormanifestations+EvidenceofS.I第23頁/共77頁Fever,bodyweight↓,tirenessTachycardiaorarrhythmiasESR↑,CRP↑,neutrocyte↑,antibodytiter↑Dignosisofactiverheumaticfever第24頁/共77頁Differentialdiagnosis

Fever

Carditis

Arthritis第25頁/共77頁DifferentialdiagnosisofcarditisInfectiveendocarditis：

anemia,splenomegaly,petechia,embolismbloodculture（+）vegetationsonendocardium/valvesViralmyocarditis：

arrhythmias(prematurecontraction)evidenceofviralinfection

第26頁/共77頁DifferentialdiagnosisofarthritisSystemiclupuserythematosus(SLE):

malarrash,proteinuria,hypertension,leukopenia,Coombs(+)hemolyticanemia,antinuclearantibodies(+)Juvenilerheumatoidarthritis(JRA)：

morningstiffness,iridocyclitis,progressionofjointdestruction,ANA(+),rheumatoidfactor(+)第27頁/共77頁Bedrest

antibiotics

anti-rheumatismtherapy

heteropathyManagement第28頁/共77頁（1）Bedrest

carditiscardiamegalycongestiveheartfailure------2w2w+----4w4w++--6w6w+++8w3mon第29頁/共77頁（2）antibioticsProcainepenicillinG:

4.8millonU~9.6millonU/d，ivdrip×2~3w

PG

AST(+):

Erythromycinp.o×10d（3）anti-rheumatismtherapyCarditis：Prednisone,2mg/kg.d(≤60mg/d)×2~4w;reducedosegradually;fullduration=8~12warthritis：Aspirin,80~100mg/kg.d(≤3g/d)untilremission;graduallyreducetohalfdosefor4~6w第30頁/共77頁（4）heteropathy

congestiveheartfailure：steroid;oxygentherapy;diuresis;captopril；digitalis(smalldose)chorea：tranquilizer(chlorpromazine,barbital)

arthralgia:

immobilizationofaffectedjoints第31頁/共77頁prophylaxis

Recurrentrheumaticfever

benzathinePenicillin:1.2millionU,Q4W,≥5yearspatientswithestablishedheartdiseasemaycontinuefor≥10years,eventhewholelife.PG

AST(+):

Erythromycinp.o×6~7d,everymonth

BacterialEndocarditis

Patientswithrheumaticheartdiseaseshouldreceiveantibioticprophylaxisbeforeandafteroperationtopreventbacterialinfection.第32頁/共77頁EmphasesFivemajorclinicalmanifestationsJonescriteriaFeaturesofactiverheumaticfevertreatment：prophylaxis：long-actingPG第33頁/共77頁Kawasakidisease（Mucocutaneouslymphnodesyndrome）川崎病第34頁/共77頁教學(xué)目的與要求了解:病因；病理分期熟悉:輔助檢查；預(yù)后掌握:臨床表現(xiàn)；診斷；

治療原則第35頁/共77頁

TomisakuKawasakidescribedKDin1967

KDisaacutegeneralizedsystemicvasculitisofunknownetiologywithfeverandrashes.CoronaryarterydilationoraneurysmsKDhasreplacedacuterheumaticfeverasthemostcommoncauseofacquiredheartdiseaseinchildrenIndevelopedcountries第36頁/共77頁Age：<4

yearsold(80%)<2

yearsold(50%)Sex：moreofteninmalesthaninfemales(1.5:1)Season：clustersinwinter/spring

Racialbackground:Asianchildren,especiallythoseofJapanesedescent.Epidemiology第37頁/共77頁EtiologyandPathogenesis

etiologyofKDremainsundiscovered.immunopathogenicmechanismforcoronarydiseaseorganismsuper-antigen

mimicantigen(HSP65)Tcell-mediatedimmuneresponsecytokine–mediatedimmunedamage第38頁/共77頁stageⅠ：1~10d，acutesmallperiarteritis；cardiacinflammatorychangesstageⅡ：10~25

d，coronaryarteritis;elasticlaminaeandmuscularlayerssplit,leadingtothrombusandaneurysms.stageⅢ：26~31

d，acuteinflammationremission;fibroustissueproliferates;intimathickens;coronaryarteriesnarroworocclude.stageⅣ：≧40d,cicatrizationinmyocardium;

occludedarteriesreopen.Pathophysiology

—systemicvasculitis(coronaryarteries)第39頁/共77頁normal

coronaryartery

stageⅠstageⅡ第40頁/共77頁10daysaftertheonsetofsymptoms,elasticlaminaesplits,intimaproliferatesandthickensinbranchofcoronaryartery.

第41頁/共77頁Hugecoronaryarteryaneurysm第42頁/共77頁Clinicalmanifestation

Mucocutaneouslymphnodeabnormalities

Cardiovascularabnormalities

Othernonspecificallymanifestations第43頁/共77頁Mainclinicalfeatures1.Feverusuallymorethan39°C,foratleast5daysHighspikingandremittentnotrespondstoantibioticsGenerallypersists1-2weekswithouttreatmentusuallyresolvesin1-2daysaftertreatmentwithintravenousgammaglobulin(IVIG)第44頁/共77頁2.BilateralconjunctivainjectionwithoutexudateMainclinicalfeatures第45頁/共77頁Mainclinicalfeatures3.inflammationofthelipsandoralcavityInjected,dry,fissured-lipsinjectedoralandpharyngealmucosaStrawberrytonguewithprominentpapillaeanderythemanooralexudates,ulcerations,orKoplikspots第46頁/共77頁Mainclinicalfeatures4.HandsandfeetErythema,orindurativeedemaofpalmsandsolesPeriungualmembranousdesquamationoffingersandtoesabout2weeksafteronsetTransversegroovesacrossthenails第47頁/共77頁Mainclinicalfeatures5.rashofvariousformsdiffuse,scarlatiniformorerythemapolymorphousrasherythemaordesquamationinperinealregion第48頁/共77頁Mainclinicalfeatures6.non-purulentcervicallymphadenopathy50-75%ofpatientsWithanodesizeof1.5cmorgreaterindiametertenderness,notred第49頁/共77頁1.

carditisTachycardiaGalloprhythm

systolicmurmursArrhythmia2.myocardialischemia

anginamyocardialinfarctionCardiovascularabnormalities第50頁/共77頁3.Coronaryarterialchanges

—2~4weeksafteronset/convalescent

phase

coronaryarteritisvesselintimaroughened

coronaryarteriesnarrow

coronaryarteriesdilation

coronaryarteryaneurysm第51頁/共77頁冠狀動脈瘤（CoronaryArteryAneurysm）最早于發(fā)病第6天檢出，8～12周明顯急性期發(fā)生率最高為25～30%，恢復(fù)期發(fā)生率10～20%。急性期一過性冠狀動脈擴(kuò)大（46%）持續(xù)性冠狀動脈瘤（21%）：多數(shù)1～2年內(nèi)恢復(fù)，約5-6%不恢復(fù)。主要累及冠狀動脈主干近端

第52頁/共77頁Aneurysmatleftanteriordescending(LAD)coronaryarteryLADCoronaryArteryAneurysm

—

20~30%ofuntreatedchildren冠狀動脈瘤發(fā)生率：左前降支＞左冠狀動脈主干、右冠狀動脈＞左回旋支左回旋支第53頁/共77頁HighriskfactorsofCAaneurysm

age:<6monthor>3yearsmalesexfeverformorethan16daysorrecurrencecardiomegalyorarrhythmialabfindings:

Hb<80g/L,WBC>16~30X109/L,PLT>1000X109/L,ESR>100mm/hKDrecurrence第54頁/共77頁Less-commonfeatures

asepticmeningitisabdominalpainotitismediajaundicediarrhea

gallbladderhydropshepaticdysfunctionarthralgiaarthritisurethritis第55頁/共77頁Bloodanalysis：

WBC↑;mildanemia;PLT↑in2nd~3thweek；

ESR↑；

CRP↑；

ALT↑;AST↑

Laboratoryfindings第56頁/共77頁Immunesystem

IgG、IgM、IgA、IgE↑；

CirculatingImmuneComplexes

↑；C3

normalor↑第57頁/共77頁ECG：ST-T

abnormalitiesofpericarditisormyocardialinfarction

非特異性ST-T變化；心律失常;心包炎時廣泛ST段抬高、低電壓；心肌梗死時ST段明顯抬高、T波倒置、病理性Q波；Chestroentgenogram：nonspecificperihilarorparenchymainfiltrates；

cardiamegaly.第58頁/共77頁Echocardiography

coronaryarteritisintimaroughened

coronaryarteriesnarrowordilation

coronaryarteryaneurysm

pericardialeffusion

mitral,aortic,ortricuspiddisturbedflowcoronaryarteryaneurysmrightcoronaryarterytrunkaorta第59頁/共77頁

冠狀動脈擴(kuò)張：

冠狀動脈內(nèi)徑>正常范圍冠狀動脈內(nèi)徑與主動脈根部內(nèi)徑之比>0.3

正常冠狀動脈主干內(nèi)徑

0～3歲<2.5mm3～

9歲

<3mm9～

14歲<3.5mm

冠狀動脈擴(kuò)張的分級輕度3mm＜冠狀A(yù)直徑≤4mm

中度4mm＜冠狀A(yù)直徑≤7mm

重度冠狀A(yù)直徑≥8mm（冠狀動脈瘤）第60頁/共77頁Coronaryangiography

—myocardialischemia/multiplecoronaryaneurysmsnormalaneurysmLADdilationandnarrow第61頁/共77頁Diagnosticguidelines

(fortypicalcases)feverlastingmorethan5days+4ofthefollowing5criteria(otherillnessesmustbeexcluded):

1.polymorphousrash2.bilateralconjunctivalinjectionwithoutexudatediffuseinjectionoforalmucosa,erythemaorfissuringofthelips,strawberrytongue4.nonpurulentcervicallymphnodeenlargement(onelymphnode>1.5cm)5.extremitychanges:erythemaofpalms/soles,indurativeedemaofhands/feet,Membranousdesquamationofthefingertips第62頁/共77頁Diagnosticguidelines

(foratypicalcases)feverlastingmorethan5days

≤3ofthe5criteria

coronaryarteriesdilationoraneurysmdetectedbyechocardiography

第63頁/共77頁DifferentialdiagnosisScarletfever

Redrashblancheswithpressure,whichisdiffusebutsparesthepalms,soles,andface.Thefaceappearsflushed.Theskinrashfadesinaweekandisfollowedbyextensivedesquamation.PatienthasgoodresponsetoPG.第64頁/共77頁DifferentialdiagnosisExudativeandErythemaMultiforme

polymorphousErythema,herpesandextensivedesquamation;oralulcers;conjunctivalexudate;noindurativeedemaofpalmsorsoles第65頁/共77頁

relievevasculitisinhibitPLTaggregationTreatment&Medication第66頁/共77頁（1）aspirin

administeredforanti-inflammatoryandantithromboticeffects

acutephase:30-100mg/kg/dPOintid/qid72hafterdefervescence:reducedosegradually2weeksafterdefervescence:3-5mg/kg/dp.o×6~8weeksuntilESR,PLTandcoronaryarteriesreturntonormal（?<3mm）第67頁/共77頁reducetheprevalenceofcoronaryabnormalitiesandleadtorapi