结缔组织病

什么是非典型结缔组织病？

非典型结缔组织病（UndifferentiatedConnectiveTissueDisease,UCTD）是一组具有结缔组织病（CTD）的某些临床或实验室特征，但不符合任何特定结缔组织病（如系统性红斑狼疮、类风湿关节炎、干燥综合征等）诊断标准的疾病状态。它介于健康状态与典型自身免疫病之间的“灰色地带”，可能是某些自身免疫病的早期或不完全表现形式。一、核心特征临床表现多样但不典型：常见症状：关节痛、雷诺现象（手指遇冷变白/紫）、轻度皮疹、疲劳、低热、口腔溃疡等；缺乏典型器官损害：如狼疮的肾脏受累、硬皮病的皮肤硬化等。实验室指标轻度异常：抗核抗体（ANA）阳性（通常低滴度，如1:80-1:320），但无特异性抗体（如抗dsDNA、抗Sm、抗SSA/SSB等）；补体水平正常或轻度降低。病程不明确：部分患者长期稳定，部分可能进展为典型结缔组织病（如10%-30%最终发展为系统性红斑狼疮、干燥综合征等）。二、诊断标准目前尚无国际统一标准，但通常需满足以下条件：存在结缔组织病相关症状（至少1项）：关节炎、雷诺现象、浆膜炎（胸膜炎/心包炎）、不明原因发热等。实验室异常（至少1项）：ANA阳性、抗磷脂抗体阳性、补体降低等。不符合任何特定CTD诊断标准：排除系统性红斑狼疮（SLEDAI评分不足）、类风湿关节炎（无侵蚀性关节炎）、硬皮病（无皮肤硬化）等。三、与非典型抗磷脂综合征（Non-criteriaAPS）的区别UCTD：以结缔组织炎症为主，可能伴轻度抗体异常。非典型APS：以血栓或产科并发症为核心，抗磷脂抗体阳性但未达实验室诊断标准。四、治疗与管理目标：控制症状、预防进展为典型CTD、减少器官损伤。具体措施：对症治疗：关节痛/发热：非甾体抗炎药（NSAIDs，如布洛芬）；雷诺现象：保暖、钙通道阻滞剂（如硝苯地平）。免疫调节：轻症：羟氯喹（200-400mg/天），兼具抗炎和免疫调节作用；重症（如浆膜炎）：短期小剂量糖皮质激素（如泼尼松10-20mg/天）。监测与随访：每6-12个月复查抗体谱、补体、血尿常规等，警惕疾病进展。五、预后稳定型：约50%-70%患者长期保持病情稳定，无需强化治疗。进展型：约20%-30%在5-10年内发展为典型CTD（如系统性红斑狼疮、干燥综合征）。危险信号：出现高滴度特异性抗体（如抗dsDNA）、补体显著降低、新发器官损害（如蛋白尿）。六、患者常见疑问“会遗传吗？”自身免疫病有遗传倾向，但非直接遗传，环境因素（感染、压力）更重要。“需要终身服药吗？”若无进展，可能仅需间歇用药；若进展为典型CTD，需长期管理。“如何预防恶化？”避免日晒（防狼疮触发）、戒烟（防血管痉挛）、定期随访。总结非典型结缔组织病是自身免疫异常的早期或温和表现，需通过定期监测和个体化治疗平衡干预与观察。关键是与主诊医生保持沟通，警惕疾病演变信号！

石丽雅医生的科普号

2025年04月06日

150

0

抗核抗体1：:80、1:100、1:1000，抗核抗体到底是什么呢，阳性就是结缔组织病吗？

一、抗核抗体：揭开神秘面纱抗核抗体，听起来挺高大上的，其实它就是一组针对细胞核内的DNA、RNA、蛋白质或这些物质的分子复合物产生的自身抗体。换句话说，它是人体免疫系统误将自身细胞核组分当作外来敌人，从而产生的抗体。在风湿免疫科，ANA常被用作自身免疫性疾病的一项重要筛查指标。二、滴度变化：从低到高的意义当我们看到ANA的检测结果时，最直观的就是那个比值，也就是滴度。不同的滴度代表了ANA在血清中的浓度，也反映了人体免疫系统的活跃程度。1:80：这是一个相对较低的滴度。在健康人群中，ANA低滴度阳性的情况并不少见。有研究显示，健康人群的ANA阳性率约为10%～20%，且随着年龄的增长，阳性率也会有所上升。因此，如果ANA的滴度为1:80，且没有明显的临床症状，那么很可能只是生理性的低滴度阳性，无需过于担心。.1:100：这个滴度仍然处于较低水平。虽然它比1:80的阳性率要高一些，但同样不能单凭此就确诊某种疾病。如果患者伴有关节疼痛、皮疹、发热等临床症状，或者同时存在其他自身免疫相关的实验室指标异常，那么ANA1:100就可能具有一定的临床意义。.1:320：当ANA的滴度达到1:320时，其临床意义就相对增加了。这个滴度通常被视为阳性结果的阈值之一。虽然它仍然不足以独立确诊某种自身免疫性疾病，但医生通常会更加关注患者的临床表现和其他检查结果，以便进行进一步的评估。1:1000：这是一个相对较高的滴度。当ANA的滴度达到1:1000时，往往提示患者存在某种自身免疫性疾病的可能性较大。特别是在系统性红斑狼疮、类风湿关节炎、干燥综合征等结缔组织病中，ANA高滴度阳性的情况较为常见。三、阳性结果：并不等同于结缔组织病虽然ANA阳性在结缔组织病中较为常见，但阳性结果并不等同于结缔组织病。ANA阳性可能由多种原因引起，包括但不限于：自身免疫性疾病：除了结缔组织病外，ANA还可能在其他自身免疫性疾病中呈阳性，如系统性硬化症、多发性肌炎等。但这些疾病的发病率相对较低，且通常伴有其他特定的临床症状和实验室指标异常。感染性疾病：某些感染性疾病，如寄生虫感染、结核杆菌感染等，也可能导致ANA阳性。但这些疾病通常伴有明显的感染症状，且ANA的滴度往往不会特别高。肿瘤性疾病：某些肿瘤性疾病，如淋巴瘤、白血病等，也可能导致ANA阳性。但这些疾病通常伴有其他肿瘤相关的症状和体征。药物影响：某些药物，如普鲁卡因胺、肼苯哒嗪等，也可能引起ANA的异常。但这些药物引起的ANA阳性通常是在服药后的一段时间内出现，且停药后可能会逐渐恢复正常。生理性因素：正如前面提到的，健康人群中也可能存在ANA低滴度阳性的情况。这可能是由于人体细胞衰老、凋亡增加等原因导致的。这种情况下，ANA阳性通常没有临床意义，也不需要特殊治疗。四、如何正确看待ANA阳性？当我们看到ANA阳性的检测结果时，应该如何正确看待呢？不要过于紧张或恐慌。ANA阳性并不一定意味着患有结缔组织病或其他自身免疫性疾病。我们需要结合患者的临床症状、其他实验室检查结果以及影像学检查等来进行综合评估。如果ANA阳性且伴有明显的临床症状或其他实验室指标异常，那么就需要及时就医并寻求专业医生的帮助。医生会根据患者的具体情况进行进一步的检查和诊断，并制定相应的治疗方案。即使ANA阳性被确诊为某种自身免疫性疾病，也不必过于担心。随着现代医学的不断进步和发展，许多自身免疫性疾病都可以得到有效的治疗和控制。只要我们积极配合医生的治疗和建议，保持良好的生活习惯和心态，就能够战胜疾病并恢复健康。写在最后抗核抗体作为风湿免疫科的一项重要筛查指标，其阳性结果并不等同于结缔组织病或其他自身免疫性疾病。我们需要结合患者的具体情况进行综合评估，并及时就医并寻求专业医生的帮助。

盛景祖医生的科普号

2024年10月23日

2422

0

4

埃勒斯-当洛斯Ehlers-Danlos综合征的综述（2020）

埃勒斯-当洛斯Ehlers-Danlos综合征的综述（2020）AreviewofEhlers-Danlossyndrome MillerE,GroselJM.AreviewofEhlers-Danlossyndrome[J].JAAPA,2020,33(4):23-28.转载文章的原链接1：https://pubmed.ncbi.nlm.nih.gov/32175940/转载文章的原链接2：https://journals.lww.com/jaapa/fulltext/2020/04000/a_review_of_ehlers_danlos_syndrome.3.aspx AbstractEhlers-Danlossyndrome(EDS)describesagroupofheritabledisordersofconnectivetissuecomprisingmutationsinthegenesinvolvedinthestructureand/orbiosynthesisofcollagen.ThirteenEDSsubtypesarerecognized,withawidedegreeofsymptomoverlapamongsubtypesandwithotherconnectivetissuedisorders.TheclinicalhallmarksofEDSaretissuefragility,jointhypermobility,andskinhyperextensibility.AppropriatediagnosisofEDSisimportantforcorrectmultidisciplinarymanagementandisassociatedwithbetterclinicaloutcomesforpatients.Ehlers-Danlos综合征（EDS）描述了一组遗传性结缔组织疾病，包括参与胶原结构和/或生物合成的基因突变。现已确认的EDS亚型有13种，各亚型之间以及与其他结缔组织疾病的症状有很大程度的重叠。EDS的临床特征是组织脆弱，关节过度活动和皮肤过度伸展。EDS的正确诊断对于正确的多学科治疗非常重要，并且与患者更好的临床结果相关。 Keywords:Ehlers-Danlossyndrome,connectivetissuedisease,jointhypermobility关节过度活动,tissuefragility,skinhyperextensibility皮肤伸展过度,heritabledisease LearningobjectivesDescribetheclinicalpresentationofEDS.UnderstandthepotentialcomplicationsandappropriatemanagementofEDS.描述EDS的临床表现。了解EDS的潜在并发症和适当的处理方法。 KeypointsEDSdescribesagroupofheritabledisordersofconnectivetissue.ThirteenEDSsubtypesarerecognized,withawidedegreeofsymptomoverlapamongsubtypesandwithotherconnectivetissuedisorders.TheclinicalhallmarksofEDSaretissuefragility,jointhypermobility,andskinhyperextensibility.PatientswithEDSaremanagedsymptomaticallybecausetheconditionhasnoknowncure.EDS描述了一组遗传性结缔组织疾病。现已确认的EDS亚型有13种，各亚型之间以及与其他结缔组织疾病的症状有很大程度的重叠。EDS的临床特征是组织脆弱，关节过度活动和皮肤过度伸展。EDS患者需要对症治疗，因为这种疾病没有已知的治愈方法。 CASEFigure A12-year-oldgirlpresentedtoherprimarycareprovidertodiscussseveralcomplaints,includingworseningjointpainthathadstartedwhenshewasage5years.Sheparticipatedinnumerousathleticactivitiesthroughoutherchildhood,buthadbeguntolimitherphysicalactivityasherjointpainmadeitincreasinglydifficult. HistoryAtbirth,thepatientwasfoundtohaveacongenitaldislocationofherrighthip,whichwastreatedconservatively,andaright-sidedpneumothoraxthatimprovedwithoutintervention.Whenthepatientwasage11months,hermothernotedanunusualheadpostureandtookhertoapediatrician.Radiographsofherspinerevealeda24-degreerightthoracolumbarcurvature,ordextroscoliosis.Duetotheseradiographicfindings,thepatientwasreferredtoapediatricorthopedicclinic,whereMRIrevealedaC4hemivertebraandradiographsshowedasignificantsubluxationofC3onC4withflexion.Toprotectthespinalcord,thepatientunderwentananteriorandposteriorfusionofC3throughC5atage18monthsandwasplacedinahaloandcastvestfor6weeks.Atage5years,thepatientbeganhavingbilateralchronickneejointpain.Physicalexaminationatthattimerevealedexcessivepatellarmovementatbothkneejoints,andthepatientwasdiagnosedwithpatellartrackingsyndrome髌骨轨迹综合征.Whenshewasage7years,flexionandextensionradiographsofthepatient'scervicalspineshowedanterolisthesisofC2onC3withneckflexion(Figure1).Shealsowasfoundtohavearight-sidedinguinalherniaandunderwentsurgicalrepair. FIGURE1.:Flexion(A)andextension(B)radiographsofthecasepatientdemonstratinganterolisthesisoftheC2vertebraeonC3onflexionview,whichresolvesonextensionview.Alsonotepostoperativechangesofthepatient'sC3-C5vertebraefromherspinalfusionsurgery. Thepatient'skneejointpaincontinuedtoprogressuntilshewasage9years,alsospreadingtothehipandshoulderjoints.Whenshebeganseeinganorthodontistatage11years,herorthodontistnotedanabnormallyhighpalate.Atapediatricianvisitshortlyafterthepatientturnedage12years,areviewofsystemswaspositiveforchronicfatigue,easybruising,anddelayedwoundhealing.Physicalexaminationrevealedjointhypermobilityandacardiacmurmur.Herpediatricianalsonotedthehyperextensibilityandvelvetytextureofherskin.Atthisappointment,thepatientdemonstratedher“partytrick,”inwhichshewasabletoexternallyrotateherarm360degreeswhilekeepinghershoulderinaneutralposition(seevideoonwww.jaapa.com).Anechocardiogramrevealedaorticvalveinsufficiencyandmildaorticrootdilation.Overtheyears,thepatientandhermotherhadbeentoldbyseveralhealthcareprovidersthathermultiplemedicalproblemswereunrelated.However,withthenewdiagnosticfindingsandathoroughreviewofthepatient'sfullmedicalhistory,clinicianshadahighdegreeofsuspicionforEhlers-Danlossyndrome(EDS);therefore,shewasreferredtoapediatricgeneticist.ShewaslaterdiagnosedwithEDStypeII,nowknownasclassicalEDS(cEDS).GenotypingshowedaheterozygousmutationoftheCOL52Agene,confirmingthediagnosis.Intheyearsfollowingherdiagnosis,thepatientcontinuedtoreceivemedicalmonitoringanddevelopedmanymedicalconditionsknowntoberelatedtoEDS,includingmigraines,posturalorthostatictachycardiasyndrome,agradeVpatentforamenovale,anddeltagranulestoragepooldeficiency.Inaddition,shehadtostopplayingsportsduetodebilitatingjointpainshortlyafterher15thbirthday. OutcomeAtages16and17years,thepatientunderwentsurgeryonherleftandrightfeet,respectively,forrepairofhammertoesofallfivedigitsbilaterally.ContinuedimagingofhercervicalspinerevealedfurtherinstabilityofherC2onC3vertebrae(Figure2).Totreatandmonitorhervarioussymptoms,thepatientregularlyseesseveralspecialists,includingcardiology,orthopedics,internalmedicine,neurology,andEDSspecialists.Shealsoroutinelyreceivesphysicaltherapy. FIGURE2.:Radiographsofthecasepatient'srightfootbefore(A)andafter(B)surgeryonallfivedigitsforcorrectionofhammertoes. UNDERSTANDINGEDSEDSisabroadtermthatdescribesagroupofheritableconnectivetissuedisordersthatareclassifiedtogetherduetosharedphenotypicandgenotypicfeatures.1,2Thephenotypichallmarksaretissuefragility,jointhypermobility,andskinhyperextensibility.1-3Thesesharedfeaturesvaryindegreeinallsubtypes,whichhelpstodifferentiateEDSfromotherjointhypermobilitydisorders.2,4Genetically,EDSresultsfromdefectsingenesinvolvedincollagenbiosynthesisorstructure胶原蛋白的生物合成或结构.2Thesyndromeisestimatedtoaffectabout1in5,000peopleworldwide.4,6-8SincethediscoveryofEDS,fivedifferentclassificationsystemshavebeenusedbyclinicians.1,2,4TheVillefrancheNosology,whichwasthemostrecentnosologyuseduntil2017,recognizedsixEDSsubtypesaccordingtomajorandminorclinicalcriteria.1,2SincetheintroductionoftheVillefrancheNosology,researchonEDShasexpandedandnewsubtypeswerediscovered.Therefore,anupdatedclassificationsystemforEDSwasproposed.1TheInternationalConsortiumonEDS,formedin2012,devisedthe2017InternationalClassificationoftheEhlers-DanlosSyndromes,whichdelineated13clinicalsubtypesofEDSaccordingtotheirclinicalmanifestations.1,2Majorclinicalcriteriawereproposedforeachsubtype,whichprovidehighspecificityfordiagnosis.Minorcriteriaweredevelopedwithlessspecificity;theycanbeusedtosupportaclinicaldiagnosisofsuspectedEDS.2Eachsubtypewasgivenanamethatdescribesitscharacteristicphenotypicmanifestations.2EDSoncewasconsideredtobearelativelyrarecondition,butasscientificknowledgeofEDSincreases,cliniciansaroundtheworldhaveagreedthatitisunderdiagnosed.5,6Theabnormalcollagencanaffectvirtuallyeverybodysystem.5ThepresentationandseverityofEDSrangefromundetectableorverymildsymptomstosevereorevenlife-threateningdisease.6ThisheterogeneityinpresentationcanmakediagnosingEDSaclinicalchallenge.7 CLINICALSUBTYPESThe13clinicalsubtypesofEDSaccordingtothe2017InternationalClassificationoftheEhlers-DanlosSyndromesare:根据2017年《国际埃勒-丹洛斯综合征分类》，EDS的13种临床亚型是:ClassicalEDS(cEDS)VascularEDS(vEDS)KyphoscolioticEDS(kEDS)ArthrochalasiaEDS(aEDS)DermatosparaxisEDS(dEDS)Brittlecorneasyndrome(BCS)Classical-likeEDS(clEDS)SpondylodysplasticEDS(spEDS)MusculocontracturalEDS(mcEDS)MyopathicEDS(mEDS)PeriodontalEDS(pEDS)Cardiac-valvularEDS(cvEDS)HypermobileEDS(hEDS).2EachsubtypehasasetofmajorandminorcriteriatoguidecliniciansevaluatingpatientswithsuspectedEDS.2IfapatientmeetsthecriteriaforasubtypeofEDS,furtherworkupisneeded.Thesuspectedclinicaldiagnosisshouldbeconfirmedwiththeappropriatemoleculartesting分子检测. GENETICANDPATHOGENETICMECHANISMSInadditiontotheupdatedclinicalclassificationsystem,the2017InternationalClassificationoftheEhlers-DanlosSyndromesalsoproposedageneticclassificationsystem遗传学分类系统.Thissystemorganizestheclinicalsubtypesintosixgroups,AthroughF,accordingtotheirunderlyingpathogeneticmechanisms.GroupingthesubtypesinthismannerisbeneficialforboththedevelopmentoftreatmentoptionsandforguidingfutureEDSresearch.2GroupA(cEDS,vEDS,aEDS,dEDS,cvEDS):DisordersofcollagenprocessinganddisordersoftheprimarystructureofcollagenGroupB(kEDS):AdisorderofcollagenfoldingorcrosslinkingGroupC(clEDSandmEDS):DisordersofthestructureandfunctionofthemyomatrixGroupD(spEDS[B3GALT6andB4GALT7subtypes]andmcEDS):DisordersofglycosaminoglycanbiosynthesisGroupE(pEDS):AdisorderofthecomplementpathwayGroupF(spEDS[SLC39A13subtype]andBCS):Thesearebelievedtobedisordersofintracellularprocesses;however,thepathogeneticmechanismsofthesesubtypesarenotwellunderstood.BecausethegeneticmechanismofhEDSisunknown,itisnotincludedinthesegroups.2由于hEDS的遗传机制尚不清楚，因此未被列入这些类群。 INHERITANCEPATTERNSAllsubtypesofEDSexcepthEDShaveaknowngeneticbasis.EDScanbeinheritedinanautosomaldominantorrecessivemanner,orcanoccurasanovelgeneticmutation.2除hEDS外，所有EDS亚型都有已知的遗传基础。EDS可以常染色体显性遗传或隐性遗传，也可以作为一种新的基因突变发生Forexample,mEDScanbeinheritedbyeitherdominantorrecessivepattern;cEDS,vEDS,hEDS,aEDS,andpEDSallareautosomaldominant.Theremainingsubtypesareinheritedinanautosomalrecessivepattern.2Therefore,familyhistoryandgeneticcounselingareimportantwhenevaluatingapatientwithsuspectedEDS.6Geneticcounselingwillbefurtherdiscussedinthediagnosissection. PHYSICALEXAMINATIONOFHALLMARKSYMPTOMSTheextensivenumberofwaysinwhichEDSmanifestscancausemanyabnormalphysicalexaminationfindings;therefore,recognizingtheunderlyingpathologycanprovedifficult.5TherecognitionandevaluationofthehallmarksymptomsofEDS(tissuefragility,jointhypermobility,andskinhyperextensibility)areimportantfirststepsinthediagnosisandworkupofthesepatients.2,5 TissuefragilitySymptomsoftissuefragilityarecommonamongpatientswithEDSandcanmanifestinmanyways.Minormanifestationsoftissuefragilitymayincludepoorwoundhealing,dystrophicscars,andeasybruising.3Moresevereandevenlife-threateningmanifestationsoftissuefragilitycancausegastrointestinalbleeding,cerebrovascularorintracranialbleeding,andaneurysmformationandrupture.8组织脆弱的症状在EDS患者中很常见，并且可以通过多种方式表现出来。组织脆弱的轻微表现可能包括伤口愈合不良、疤痕营养不良和容易擦伤更严重甚至危及生命的组织脆弱表现可引起胃肠道出血、脑血管或颅内出血、动脉瘤形成和破裂。 JointhypermobilityThisdescriptivetermisusedtodescribeajointthathasanincreasedrangeofmotioncomparedwithanormaljoint.Generalizedjointhypermobilitymayindicatealargerunderlyingpathology.Inpatientswithgeneralizedjointhypermobility,affectedjointsaretypicallypresentinthefourlimbsandaxialskeleton.WhenconsideringadiagnosisofEDS,cliniciansmustdifferentiatebetweenasinglehypermobilejointandgeneralizedjointhypermobility.2,9Severalmethodscanbeusedtoassessgeneralizedjointhypermobility;themostcommonmethodinvolvescalculatingtheBeightonscore(Table1).9-12这个描述性术语用于描述与正常关节相比活动范围增加的关节。全身性关节过度活动可能表明更大的潜在病理。在全身性关节活动过度的患者中，受影响的关节通常存在于四肢和轴骨。当考虑EDS的诊断时，临床医生必须区分单一关节过度活动和广泛性关节过度活动2,9。有几种方法可用于评估广泛性关节过度活动;最常用的方法是计算贝顿分数(表1) TABLE1.:TheBeightonscoringsystemforevaluationofgeneralizedjointhypermobility.Foreachsymptompresentthepatientgetsonepoint.Ascoreof5orgreaterisindicativeofgeneralizedjointhypermobility.ReproducedfromSmits-EngelsmanB,KlerksM,KirbyA.Beightonscore:avalidmeasureforgeneralizedhypermobilityinchildren.JPediatr.2011;158(1):119-123,withpermissionofElsevier. UndertheBeightonscoringsystem,patientsaregivenanumericscoreonascaleof0to9;ascoreof5orgreaterindicatesgeneralizedjointhypermobility.TheupdatedEDSclassificationsystemproposesthatcliniciansusingtheBeightonscoretoassesspatientswithsuspectedhEDSmusttakepatientageintoaccountbecausejointrangeofmotiondecreaseswithage.Therefore,whenevaluatingprepubertalpatientswithsuspectedhEDS,ascoreof6orgreaterisconsideredpositive.Forpatientsofpubertalageuptoage50years,ascoreof5orgreaterisconsideredpositive,andforpatientsolderthanage50years,ascoreof4orgreaterisconsideredpositive.2 SkinhyperextensibilityEvaluateskinextensibilitybypullingthecutaneousandsubcutaneousskinlayersuntilresistanceisfelt.Theskinshouldstretcheasily,anduponreleaseshouldsnapbackintoplace.Testingshouldbeperformedinareasthatarelesslikelytoundergomechanicaltraumaorscarring.2,3通过拉皮肤和皮下皮肤层来评估皮肤的延展性，直到感觉到阻力。皮肤应该很容易伸展，释放后应该弹回原位。测试应在不太可能遭受机械创伤或疤痕的区域进行。Skinshouldbeconsideredhyperextensibleifitcanbestretchedexcessivelyinatleastthreeoftheselocations:distalforearms,dorsumofthehands,neck,elbows,orknees.2Iftheskinofthedistalforearmsanddorsumofthehandscanbestretchedatleast1.5cm,orskinoftheneck,elbow,andkneesstretchedatleast3cm,itisconsideredhyperextensible(Figure3).2如果皮肤在前臂远端、手背、颈部、肘部或膝盖至少三个部位可以过度拉伸，则应考虑皮肤过度拉伸。如果前臂远端和手背的皮肤可拉伸至少1.5cm，或颈部、肘部和膝盖的皮肤可拉伸至少3cm，则认为是超可伸性(图3)。 FIGURE3.:Thecasepatientdemonstratinghyperextensibilityofherskinatherelbow(A)andknee(B). DIAGNOSISDiagnosingEDSisconsideredcomplexforseveralreasons.5,13,14Medicalprofessionals'trainingoftendoesnotincludeacomprehensiveeducationonthediagnosisandmanagementofEDS.15Furthermore,manysignsandsymptomsmaybesubtle,andthusmaynotreadilyalertclinicianstothepossibilityofanunderlyingpathology.13FeaturesofEDSoftenoverlapwithsymptomsofotherconnectivetissuedisorders,suchasjointhypermobilitysyndrome关节过度活动综合征,Marfansyndrome马凡综合征,orosteogenesisimperfecta脆骨病.7,11,14ClinicaldifferentiationamongtheEDSsubtypesalsocanbedifficultbecauseofoverlappingclinicalfindings.2OncetheclinicianhasaclinicalsuspicionofEDSinapatient,referraltoageneticistforgenetictestingisneededtoconfirmthediagnosis.2However,hEDSistheonlysubtypethatdoesnothaveaconfirmatorygenetictest.Therefore,thediagnosisofthisconditionmustremainclinical.2PromptrecognitionofEDSoftenisnotachieved,anddiagnosistypicallyoccurslate.16Somepatientsmaybediagnosedduringtheirchildhood;othersmaynotbediagnoseduntiladulthood.17ConclusiveresearchabouttheaveragelengthoftimeuntilEDSisdiagnosedislacking;however,astudypublishedbyHamonetandcolleaguesin2018reportedanaverageof22yearsfromsymptomonsettodiagnosis.7PatientsmaybeseenbymanyhealthcareprovidersbeforereceivingadiagnosisofEDS.EarlyrecognitionanddiagnosisofEDSareassociatedwithbetterclinicaloutcomesandcanreduceunnecessaryuseofmedicalresourcesandtesting.16Anearlydiagnosisalsocanhelpreducesymptomseverity,preventcomplications,andimprovepatientqualityoflife.11,16 GENETICCOUNSELINGConsidergeneticcounselingandtestingforimmediatefamilymembersofpatientswithEDS.6ReferringtheparentsofapatientwithEDSforevaluationisappropriateeveniftheyareasymptomatic.Ifaparentisfoundtobeaffected,oriftheparent'sstatuscannotbedetermined,refersiblingsforgeneticevaluationaswell.PatientswithEDSwhowishtoconceiveshouldreceivegeneticcounselingtodiscusstheriskoftheirchildreninheritingthedisorder.18Geneticcounselingprovidespatientsandtheirfamilieswithimportantinformationabouttheinheritancepatternandimplicationsofthedisorder.This,alongwithgenetictesting,letspatientsandtheirfamiliesmakemoreinformedmedicalandpersonaldecisions.13,18 MANAGEMENTPatientswithEDSaremanagedsymptomaticallybecausetheconditionhasnoknowncure.17However,noguidelineshavebeenestablishedformanagingpatientswithEDSandtreatmentvariessignificantlyamongpatients.1Documentthepatient'ssymptomsthroughacomprehensivehistoryandphysicalexamination,thenmakereferralstotheappropriatespecialists.BecauseEDStypicallyinvolvesseveralorgansystems,managementoftenentailscollaborativeeffortsamonghealthcareprovidersfromseveralspecialties.5,16,17EDS患者的治疗是对症的，因为这种病没有已知的治愈方法。然而，目前还没有针对EDS患者的管理指南，而且不同患者的治疗方法也有很大差异，通过全面的病史和体格检查记录病人的症状，然后转诊给适当的专科医生。由于EDS通常涉及多个器官系统，因此管理通常需要来自多个专业的医疗保健提供者之间的协作努力。Patienteducationisanimportantcomponentofdiseasemanagement,andmayinvolvewaystopreventunwantedjointevents,suchasdislocation.17Ahealthfullifestylecanhelppatientsstrengthenjoints,preventjointinjury,andcanhelppreventincreasedjointpainlaterinlife.Inaddition,physicaltherapyandoccupationaltherapymaybebeneficial.19患者教育是疾病管理的一个重要组成部分，可能包括预防不希望发生的联合事件，如脱位的方法健康的生活方式可以帮助患者加强关节，防止关节损伤，并有助于防止晚年关节疼痛加剧。此外，物理治疗和职业治疗可能是有益的。SeveralstudieshaveshownanassociationamongEDS,psychologicaldistress,andreducedqualityoflife.5,20Manypatientsaresusceptibletoanxiety,depression,disability,andsocialisolation.15,17PatientsdiagnosedwithEDSmayneedpsychologicalsupport,andearlyinterventionmayleadtobetterclinicaloutcomes.16一些研究表明EDS、心理困扰和生活质量下降之间存在关联5,20。许多患者易患焦虑、抑郁、残疾和社会孤立15,17。诊断为EDS的患者可能需要心理支持，早期干预可能导致更好的临床结果。 SurgeryandotherproceduresPatientswithEDSmayhavecomplicationsduringroutinemedicalprocedures,surgery,andtheperioperativeperiod.Forexample,onestudyshowedthatpatientswithvEDSarehighlysusceptibletosurgicalcomplicationssuchasseverebleedingandcomplicationsofanesthesia.PatientswithEDSshouldobtainpreoperativeclearancebeforeundergoingsurgery.Cliniciansmayconsidersendingthesepatientstoaspecializedpreoperativeevaluationcenterforclearance.6EDS患者可能在常规医疗程序、手术和围手术期出现并发症。例如，一项研究表明，vEDS患者极易出现手术并发症，如大出血和麻醉并发症。EDS患者应在手术前获得术前清除。临床医生可能会考虑将这些患者送到专门的术前评估中心进行检查。 ObstetricconsiderationsConsiderreferraltoanobstetricianwhohandleshigh-riskpregnanciesforallpregnantpatientswithEDS,becausecomplicationssuchasprematureruptureofmembranes,uterinehemorrhage,oruterinerupturecanoccurduringpregnancyanddelivery.13,18考虑转诊到产科医生处理高危妊娠的所有妊娠EDS患者，因为并发症，如膜早破，子宫出血，或子宫破裂可能发生在怀孕和分娩期间。 CardiovascularproblemsEDSisassociatedwithanincreasedincidenceofcardiovascularabnormalities,suchasmitralvalveprolapseandaorticdissection.13AlthoughstandardizedguidelinesarelackingforevaluatingcardiovascularabnormalitiesinpatientswithEDS,baselineechocardiogramsoftenareobtainedatthetimeofdiagnosis.13Aorticdiametermeasurementalsoisrecommended,andmayrequireadditionalevaluationwithCTorMRIangiographyifvisibilityonechocardiogramislimited.7,13ReferraltoacardiologistofteniswarrantedforpatientswithEDS.16,19EDS与心血管异常的发生率增加有关，如二尖瓣脱垂和主动脉夹层虽然缺乏标准化的指南来评估EDS患者的心血管异常，但在诊断时通常可以获得基线超声心动图主动脉直径测量也是推荐的，如果超声心动图上的可见性有限，可能需要额外的CT或MRI血管造影评估7,13。对于EDS患者，转诊给心脏病专家通常是有保证的。 ChronicpainThisisoneofthemostcommoncomplaintsinpatientswithEDS,andcanimpairpatients'schoolandworklives,personalrelationships,andpsychologicalwell-being.TreatingpaininpatientswithEDScanbechallengingandmayrequirereferraltoapainspecialist.21-23Managementtypicallyinvolvesamultimodalapproach,usingsuchmethodsasphysical,occupationalandcognitivebehavioraltherapies,pharmacologicagents,splintingofunstablejoints,compressiongarments,shoeinserts,andspecializedexerciseprograms.22,23这是EDS患者最常见的主诉之一，并且会损害患者的学习和工作生活、人际关系和心理健康。治疗EDS患者的疼痛是具有挑战性的，可能需要转介到疼痛专家21-23。典型的治疗包括多模式的方法，使用诸如物理、职业和认知行为疗法、药物、不稳定关节夹板、压缩服装、鞋垫和专门的锻炼计划等方法。Opioidsmaybeusefulinthesepatients,butshouldbeusedwithcaution.Onestudyfoundthat,comparedwithage-matchedcontrols,patientswithEDSareprescribedopioidsmorefrequentlyandathigherdosesthanpatientswhodonothaveEDS.Chronicopioidusecanleadtotoleranceandanincreasedriskfordependence.21阿片类药物可能对这些患者有用，但应谨慎使用。一项研究发现，与年龄匹配的对照组相比，EDS患者比没有EDS的患者更频繁地服用阿片类药物，剂量也更高。长期使用阿片类药物可导致耐受性和依赖性风险增加。 CONCLUSIONEDSisacomplexdiseasecausedbymutationsingenesinvolvedinthestructureandbiosynthesisofcollagen.ThenewestEDSclassificationsystemcanserveasadiagnosticframeworkforclinicalevaluationofpatientswithsuspectedEDS.Thediagnosisshouldbeconfirmedwiththeappropriategenetictesting.Promptrecognition,diagnosis,andinitiationoftreatmentinpatientswithEDSareassociatedwithbetterclinicaloutcomesandqualityoflife.AlthoughanupdatedsystemfordiagnosingthesubtypesofEDShasbeenestablished,nostandardcriteriaexistformanagingthesyndrome;referraltomultiplemedicalspecialiststypicallyisrequired.EDS是一种复杂的疾病，由参与胶原结构和生物合成的基因突变引起。最新的EDS分类系统可作为临床评估疑似EDS患者的诊断框架。诊断应通过适当的基因检测来证实。EDS患者的及时识别、诊断和开始治疗与更好的临床结果和生活质量相关。虽然已经建立了诊断EDS亚型的最新系统，但没有管理该综合征的标准准则;通常需要转介给多名医学专家。