炎性肌病和系统性血管炎

Theidiopathicinflammatorymyopathies(IIMs)areagroupofrare,systemicautoimmunediseasescharacterizedclinicallybyprogressiveproximalmuscleweaknesshistopathologicallybythepresenceofinflammatorycellsinmuscletissueDefinition1Polymyositis(PM)

Dermatomyositis(DM)JuvenileDMNecrotizingmyopathy(IMNM)Sporadicinclusionbodymyositis(sIBM)separateIIMsubtypes:DMIBMPMusuallyinthelateteensorolder;themeanageatonset

being40to60years;F:Mratio>2:1)twopeaks—5to15years

45to65yearsF:Mratio>2:1)inindividualsolderthan50years;rareinyoungeradults5Muscleweaknessslowonsetofmusclefatigue,painandatrophyprogressiveweaknessofproximallimbmusclesCLINICALFEATURES3SkinsymptomsGottron’ssignsHeliotroperashV-signShawlsignPeriorbitaloedemaMechanic’shand8Raynaud’sphenomenonCalcinosiscutisUlcerationArthritisJointpainandarthritisarecommonarthritisistypicallynonerosiveMostfrequently,arthritisisseeninpatientswithanti–Jo-1AbandotherantisynthetaseAbs.LungDyspneaandcougharecommon.weaknessoftherespiratorymusclesinflammationofthelungtissue(interstitiallungdisease)LunginvolvementisfrequentinPMandDMandisamajorriskfactorformortality.HeartCardiacinvolvementmaybeoverlookedconductionabnormalitiesandarrhythmiasMyocarditis,resultinsuddendeathCK-MB/totalCKratiomaybegreaterthan3%increasedserumlevelsofcardiacisoformtroponinI12GastrointestinalTractDifficultyswallowingReflux,weaknessintheloweresophagusMusclestrengthTheskinshouldalsobeexaminedtodetectchangesincludingthoseinnailfoldsandthescalp.Jointscanbeaffectedbyarthritis,heartandlungchangesshouldbecarefullylookedfor.PHYSICALEXAMINATION4BiochemicalMeasuringserumlevelsofmuscleenzymesImmunologicANAsarefoundinapproximately60%to70%ofmyositispatients.LABORATORYEVALUATION5Myositis-specificautoantibodies2024/6/8Myositis–associatedautoantibodiesAnti-RNPAnti-SSAAnti-SSBElectromyographyElectromyogram(EMG)changesareusuallynonspecificbutareausefulindicatorofmyopathicchanges.插入电位：肌病急性期或活动期插入电位活动性增强，慢性期减弱纤颤电位和正锐波：异常的自发放电自发奇异高频放电：提示炎性肌病低波幅，短时限，多相运动单位电位鉴别是肌源性的？还是神经源性的？Imagingthesymmetricinflammationintheaffectedmuscle多为对称性病变。T1等信号，T2高信号，提示肌肉炎性水肿部位。

BohanandPeterCriteriaforPolymyositisandDermatomyositis,1975DIAGNOSIS

6PM确诊：符合所有1~4条；DM确诊：第5条及1~4条中任3条。2024/6/8DM皮疹PM发病机制不同病理不同2024/6/8PolymyositisDermatomyositis周围血活化T细胞明显增多，但功能下降活化B细胞明显增多肌细胞和肌内膜CD8+T细胞（内有穿孔素、颗粒酶）浸润CD8+T细胞少肌束膜和血管周围区B细胞少CD4+T细胞，B细胞，血管壁膜攻击复合物（MAC）沉积肌细胞表面表达抗原类型MHC-IMHC-II免疫异常细胞免疫为主体液免疫为主损伤组织肌纤维小血管损伤为先，继发肌肉损伤PM：发病起于CD8+T细胞识别肌细胞表面MHC-1，分泌穿孔素和颗粒酶，损伤肌细胞。束周萎缩血管周围炎明显DM：发病起于MAC在血管壁沉积及对血管内皮细胞直接损伤，有CD4+T细胞和B细胞参与，继而肌肉损伤。2024/6/8分类标准敏感性（95%CI）特异性（95%CI）B&P（1975）94%（77-99）23%（6.0-54）ENMC（2004）68%（49-83）85%（54-97）分类诊断标准的演进2024/6/8ClassificationcriteriaforIIM(exceptIBM),proposedbyENMC,2004ClinicalcriteriaserumcreatinekinaselevelOtherlaboratorycriteria:MSAsandMRIofmuscletissueswereincludedMusclebiopsyMusclebiopsyisthe“goldstandard”forthediagnosisofinflammatorymyopathiesandacriticalcomponentofthedefinitivediagnosisofIIMs.26ClassificationcriteriaforIIM(exceptIBM),proposedbyENMC,2004Components:ClinicalcriteriaInclusioncriteria:(a)Onsetusuallyover18years(post-puberty),onsetmaybeinchildhoodinDMandnon-specificmyositis(b)Subacuteorinsidiousonset(c)Patternofweakness:symmetric,proximal>distal,neckflexor>neckextensor(d)RashtypicalofDM:heliotrope(purple);periorbitaloedema;Gottron’ssign;V-signandshawlsignExclusioncriteria:(a)ClinicalfeaturesofIBM(seeGriggsetal.(AnnNeurol1995;38:705–13):asymmetricweakness,wrist/fingerflexorssameorworsethatdeltoids;kneeextensorsand/orankledorsiflexorssameorworsethanhipflexors)(b)Ocularweakness,isolateddysarthria,neckextensor>neckflexorweakness(c)Toxicmyopathy(e.g.recentexposuretomyotoxicdrugs),activeendocrinopathy(hyper-orhypothyroid,hyperparathyroid),amyloidosis,familyhistoryofmusculardystrophyorproximalmotorneuropathies(e.g.SMA)ElevatedserumcreatinekinaselevelOtherlaboratorycriteria:ElectromyographyMRI:diffuseorpatchyincreasedsignal(oedema)withinmuscletissueonSTIRimages(c)Myositis-specificantibodiesdetectedinserum29Musclebiopsy:(a)Endomysialinflammatorycellinfiltrate(T-Cells)surroundingandinvadingnon-necroticmusclefibresPM(b)EndomysialCD8+T-cellssurrounding,butnotdefinitelyinvadingnon-necroticmusclefibres,orubiquitousMHC-1expressionPM(c)PerifascicularatrophyDM(d)MACdepositionsonsmallbloodvessels,orreducedcapillarydensity,ortubuloreticularinclusionsinendothelialcellsonEM,orMHC-1expressionofperifascicularfibresDM(e)Perivascular,perimysialinflammatorycellinfiltrateDM(f)ScatteredendomysialCD8+T-cellsinfiltratethatdoesnotclearlysurroundorinvademusclefibres(g)Manynecroticmusclefibresasthepredominantabnormalhistologicalfeature.Inflammatorycellsaresparceoronlyslightperivascular;perimysialinfiltrateisnotevident.MACdepositiononsmallbloodvesselsorpipestemcapillariesonEMmaybeseen,buttubuloreticularinclusionsinendothelialcellsareuncommonornotevident.Immune-mediatednecrotizingmyopathy(h)Rimmedvacuoles,raggedredfibres,cytochromeoxidase-negativefibresthatwouldsuggestIBM(i)MACdepositiononthesarcolemmaofnon-necroticfibresandotherindicationsofmusculardystrophieswithimmunopathologyClassificationcriteriaforIIMPolymyositis

Definitepolymyositis:1.Allclinicalcriteriawiththeexceptionofrash2.ElevatedserumCK3.Musclebiopsycriteriaincludea;andexcludec;d;h;iEndomysialinflammatorycellinfiltrate(T-Cells)surroundingandinvadingnon-necroticmusclefibresPMEndomysialCD8+T-cellssurrounding,butnotdefinitelyinvadingnon-necroticmusclefibres,orubiquitousMHC-1expressionDermatomyositisDefinitedermatomyositis:1.Allclinicalcriteria2.Musclebiopsycriteriaincludec;PerifascicularatrophyDMMACdepositionsonsmallbloodvessels,orreducedcapillarydensity,ortubuloreticularinclusionsinendothelialcellsonEM,orMHC-1expressionofperifascicularfibres2024/6/8DIFFERENTIALDIAGNOSIS72024/6/8DIFFERENTIALDIAGNOSIS2024/6/8DIFFERENTIALDIAGNOSIS2024/6/8抗Jo-1抗体抗PL-7抗体抗PL-12抗体抗EJ抗体抗KS抗体抗OJ抗体抗Ha抗体抗Zo抗体抗合成酶抗体综合征肌炎肺间质病变关节炎发热雷诺现象技工手AntisynthetaseSyndromeNecrotizingmyopathy(NM)immune-mediatednecrotizingmyopathyornecrotizingautoimmunemyopathy,ThisgroupofNMisheterogeneousandincludes:autoimmuneinflammatorymechanisms,paraneoplasticconditions,exposuretotoxinsordrugs38Themajorfindingsarescatterednecroticmusclefibres.Sparseinflammatorycellsmaysurroundthenecrosis.Macrophagesarepredominantandfewlymphocytesarepresent,whichwereidentifiedasCD4+andCD8+TcellsMusclebiopsy:MostpatientswithSRPautoantibodiesfulfillthecriteriaforNM;Two-thirdsofmyositispatientswithHMGCRautoantibodieshavepreviouslybeenexposedtostatins.Inclusionbodymyositis老年男性多见，起病隐匿，近端肌群和远端肌群均可受累，不对称，肌细胞胞浆中或胞核内有管状或丝状包涵体肌细胞内可见嗜酸性包涵体，包涵体旁充满了碱性颗粒的带边空泡TREATMENT82024/6/8

SystemicVasculitisVasculitisisaheterogeneousgroupofdisorderslinkedby

theprimaryfindingofinflammationwithinbloodvesselwalls.以血管的炎症与坏死为主要病理改变，常累及全身多个系统，也可局限在某一脏器。临床表现各异，最常累及的部位是皮肤、肾脏、肺、神经系统等。44动脉的种类：1）大动脉是近心的动脉，包括主动脉、肺动脉、无名动脉、颈总动脉、锁骨下动脉等等2）中动脉除主动脉、肺动脉等大动脉外，在解剖学中有名称的动脉大多属于中动脉。3）小动脉管径在0.3～1mm的动脉4）微动脉管径在0.3mm以下的动脉45血管炎的分类大血管性血管炎小血管性血管炎

—巨细胞（颞）动脉炎

—韦格纳肉芽肿

—大动脉炎—Churg-Strauss综合征中等血管性血管炎

—显微镜下多血管炎

—结节性多动脉炎—Henoch-Schonlein紫癜

—川崎病

—冷球蛋白血症性血管炎

—皮肤白细胞破碎性血管炎1993ChapelHill共识会议2024/6/8ChapelHill1993分类优缺点优点缺点简单未说明同一血管炎可能累及不同大小的血管（BD，Cogan）宜于临床工作未提及发病机制ANCA继发性血管炎等未归入2024/6/8ChapelHill2012Classification旧血管炎分类LargeVesselvasculitisMediumVesselvasculitisSmallVesselvasculitis新增加的血管炎分类VariableVesselvasculitisSingleOrganvasculitisVasculitisAssociatedwithSystemicDiseaseVasculitiswithProbableEtiology2024/6/82024/6/8新增加的血管炎分类ACRclassificationcriteriaforTakayasu’sArteritis左锁骨动脉闭塞右肾动脉狭窄ACRclassificationcriteriaforGiantcell

arteritisPolyarteritisNodosa

Polyarteritisnodosa(PAN),characterizedbynecrotizingvasculitisofmedium-sizedarterieswithfewornoimmunedeposits.Smallarteriesmayalsobeinvolved,butsmallvessels,includingarterioles,capillaries,andvenules,arenot.2024/6/8Clinicalmanifestation:TheocclusionorruptureofinflamdarteriesmightproducetissueischemiaorhemorrhageinavarietyoforgansandsystemsNotaffectlung,notcauseglomerulonephritis,andnoANCApositiveTheperipheralnervoussystemandtheskinarethemostfrequentlyinvolvedterritoriesOrchitisis（睾丸炎）themostcharacteristicsymptomofPAN.睾丸炎，腓肠肌痛，垂腕、垂足（单神经炎）、肾功不全和肾性高血压活检部位：皮肤（深达皮下脂肪层）、腓肠肌、腓浅神经等。AntineutrophilCytoplasmAntibody–AssociatedVasculitis显微镜下多动脉炎（MPA），肉芽肿性多动脉炎（GPA）和嗜酸性肉芽肿性多动脉炎（EGPA）髓过氧化物酶（MPO）和蛋白酶3（PCR3）是ANCA的主要靶抗原ANCA相关性血管炎是一种常见的累及多系统的自身免疫性疾病，多累及肺、肾和神经系统。c-ANCAp-ANCA蛋白酶-3（PR3）髓过氧化物酶（MPO)56Granulomatosiswithpolyangiitis（GPA）Granulomatousinflammationinvolvingtherespiratorytractandnecrotizingvasculitisaffectingsmalltomedium-sizedvessels(capillaries,venules,arterioles,arteries)CriteriaforclassificationofGPA58EosinophilicgranulomatosiswithpolyangiitisEosinophil-richandgranulomatousinflammationinvolvingtherespiratorytractandnecrotizingvasculitisaffectingsmalltomedium-sizedvessels,associatedwithasthmaandbloodeosinophiliaCriteriaforclassificationofEGPA60Microscopicpolyangiitis（MPA）Necrotizingvasculitiswithfewornoimmunedepositsaffectingsmallvessels(capillaries,venules,arterioles)DifferentialdiagnosticFeaturesoftheANCA-AssociatedVasculitidesImmuneComplex–MediatedSmallVesselVasculitisCutaneousinvolvementofsmallbloodvesselsisthemostprominentfeatureinthemajorityofcases,Behçet’sDiseaseBehçet’s