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結(jié)締組織病科普知識 查看全部

什么是非典型結(jié)締組織??？非典型結(jié)締組織?。║ndifferentiatedConnectiveTissueDisease,UCTD）是一組具有結(jié)締組織?。–TD）的某些臨床或?qū)嶒?yàn)室特征，但不符合任何特定結(jié)締組織?。ㄈ缦到y(tǒng)性紅斑狼瘡、類風(fēng)濕關(guān)節(jié)炎、干燥綜合征等）診斷標(biāo)準(zhǔn)的疾病狀態(tài)。它介于健康狀態(tài)與典型自身免疫病之間的“灰色地帶”，可能是某些自身免疫病的早期或不完全表現(xiàn)形式。一、核心特征臨床表現(xiàn)多樣但不典型：常見癥狀：關(guān)節(jié)痛、雷諾現(xiàn)象（手指遇冷變白/紫）、輕度皮疹、疲勞、低熱、口腔潰瘍等；缺乏典型器官損害：如狼瘡的腎臟受累、硬皮病的皮膚硬化等。實(shí)驗(yàn)室指標(biāo)輕度異常：抗核抗體（ANA）陽性（通常低滴度，如1:80-1:320），但無特異性抗體（如抗dsDNA、抗Sm、抗SSA/SSB等）；補(bǔ)體水平正常或輕度降低。病程不明確：部分患者長期穩(wěn)定，部分可能進(jìn)展為典型結(jié)締組織?。ㄈ?0%-30%最終發(fā)展為系統(tǒng)性紅斑狼瘡、干燥綜合征等）。二、診斷標(biāo)準(zhǔn)目前尚無國際統(tǒng)一標(biāo)準(zhǔn)，但通常需滿足以下條件：存在結(jié)締組織病相關(guān)癥狀（至少1項(xiàng)）：關(guān)節(jié)炎、雷諾現(xiàn)象、漿膜炎（胸膜炎/心包炎）、不明原因發(fā)熱等。實(shí)驗(yàn)室異常（至少1項(xiàng)）：ANA陽性、抗磷脂抗體陽性、補(bǔ)體降低等。不符合任何特定CTD診斷標(biāo)準(zhǔn)：排除系統(tǒng)性紅斑狼瘡（SLEDAI評分不足）、類風(fēng)濕關(guān)節(jié)炎（無侵蝕性關(guān)節(jié)炎）、硬皮?。o皮膚硬化）等。三、與非典型抗磷脂綜合征（Non-criteriaAPS）的區(qū)別UCTD：以結(jié)締組織炎癥為主，可能伴輕度抗體異常。非典型APS：以血栓或產(chǎn)科并發(fā)癥為核心，抗磷脂抗體陽性但未達(dá)實(shí)驗(yàn)室診斷標(biāo)準(zhǔn)。四、治療與管理目標(biāo)：控制癥狀、預(yù)防進(jìn)展為典型CTD、減少器官損傷。具體措施：對癥治療：關(guān)節(jié)痛/發(fā)熱：非甾體抗炎藥（NSAIDs，如布洛芬）；雷諾現(xiàn)象：保暖、鈣通道阻滯劑（如硝苯地平）。免疫調(diào)節(jié)：輕癥：羥氯喹（200-400mg/天），兼具抗炎和免疫調(diào)節(jié)作用；重癥（如漿膜炎）：短期小劑量糖皮質(zhì)激素（如潑尼松10-20mg/天）。監(jiān)測與隨訪：每6-12個月復(fù)查抗體譜、補(bǔ)體、血尿常規(guī)等，警惕疾病進(jìn)展。五、預(yù)后穩(wěn)定型：約50%-70%患者長期保持病情穩(wěn)定，無需強(qiáng)化治療。進(jìn)展型：約20%-30%在5-10年內(nèi)發(fā)展為典型CTD（如系統(tǒng)性紅斑狼瘡、干燥綜合征）。危險信號：出現(xiàn)高滴度特異性抗體（如抗dsDNA）、補(bǔ)體顯著降低、新發(fā)器官損害（如蛋白尿）。六、患者常見疑問“會遺傳嗎？”自身免疫病有遺傳傾向，但非直接遺傳，環(huán)境因素（感染、壓力）更重要?！靶枰K身服藥嗎？”若無進(jìn)展，可能僅需間歇用藥；若進(jìn)展為典型CTD，需長期管理?！叭绾晤A(yù)防惡化？”避免日曬（防狼瘡觸發(fā)）、戒煙（防血管痙攣）、定期隨訪?？偨Y(jié)非典型結(jié)締組織病是自身免疫異常的早期或溫和表現(xiàn)，需通過定期監(jiān)測和個體化治療平衡干預(yù)與觀察。關(guān)鍵是與主診醫(yī)生保持溝通，警惕疾病演變信號！
抗核抗體1：:80、1:100、1:1000，抗核抗體到底是什么呢，陽性就是結(jié)締組織病嗎？一、抗核抗體：揭開神秘面紗抗核抗體，聽起來挺高大上的，其實(shí)它就是一組針對細(xì)胞核內(nèi)的DNA、RNA、蛋白質(zhì)或這些物質(zhì)的分子復(fù)合物產(chǎn)生的自身抗體。換句話說，它是人體免疫系統(tǒng)誤將自身細(xì)胞核組分當(dāng)作外來敵人，從而產(chǎn)生的抗體。在風(fēng)濕免疫科，ANA常被用作自身免疫性疾病的一項(xiàng)重要篩查指標(biāo)。二、滴度變化：從低到高的意義當(dāng)我們看到ANA的檢測結(jié)果時，最直觀的就是那個比值，也就是滴度。不同的滴度代表了ANA在血清中的濃度，也反映了人體免疫系統(tǒng)的活躍程度。1:80：這是一個相對較低的滴度。在健康人群中，ANA低滴度陽性的情況并不少見。有研究顯示，健康人群的ANA陽性率約為10%～20%，且隨著年齡的增長，陽性率也會有所上升。因此，如果ANA的滴度為1:80，且沒有明顯的臨床癥狀，那么很可能只是生理性的低滴度陽性，無需過于擔(dān)心。.1:100：這個滴度仍然處于較低水平。雖然它比1:80的陽性率要高一些，但同樣不能單憑此就確診某種疾病。如果患者伴有關(guān)節(jié)疼痛、皮疹、發(fā)熱等臨床癥狀，或者同時存在其他自身免疫相關(guān)的實(shí)驗(yàn)室指標(biāo)異常，那么ANA1:100就可能具有一定的臨床意義。.1:320：當(dāng)ANA的滴度達(dá)到1:320時，其臨床意義就相對增加了。這個滴度通常被視為陽性結(jié)果的閾值之一。雖然它仍然不足以獨(dú)立確診某種自身免疫性疾病，但醫(yī)生通常會更加關(guān)注患者的臨床表現(xiàn)和其他檢查結(jié)果，以便進(jìn)行進(jìn)一步的評估。1:1000：這是一個相對較高的滴度。當(dāng)ANA的滴度達(dá)到1:1000時，往往提示患者存在某種自身免疫性疾病的可能性較大。特別是在系統(tǒng)性紅斑狼瘡、類風(fēng)濕關(guān)節(jié)炎、干燥綜合征等結(jié)締組織病中，ANA高滴度陽性的情況較為常見。三、陽性結(jié)果：并不等同于結(jié)締組織病雖然ANA陽性在結(jié)締組織病中較為常見，但陽性結(jié)果并不等同于結(jié)締組織病。ANA陽性可能由多種原因引起，包括但不限于：自身免疫性疾?。撼私Y(jié)締組織病外，ANA還可能在其他自身免疫性疾病中呈陽性，如系統(tǒng)性硬化癥、多發(fā)性肌炎等。但這些疾病的發(fā)病率相對較低，且通常伴有其他特定的臨床癥狀和實(shí)驗(yàn)室指標(biāo)異常。感染性疾?。耗承└腥拘约膊。缂纳x感染、結(jié)核桿菌感染等，也可能導(dǎo)致ANA陽性。但這些疾病通常伴有明顯的感染癥狀，且ANA的滴度往往不會特別高。腫瘤性疾?。耗承┠[瘤性疾病，如淋巴瘤、白血病等，也可能導(dǎo)致ANA陽性。但這些疾病通常伴有其他腫瘤相關(guān)的癥狀和體征。藥物影響：某些藥物，如普魯卡因胺、肼苯噠嗪等，也可能引起ANA的異常。但這些藥物引起的ANA陽性通常是在服藥后的一段時間內(nèi)出現(xiàn)，且停藥后可能會逐漸恢復(fù)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低滴度陽性的情況。這可能是由于人體細(xì)胞衰老、凋亡增加等原因?qū)е碌?。這種情況下，ANA陽性通常沒有臨床意義，也不需要特殊治療。四、如何正確看待ANA陽性？當(dāng)我們看到ANA陽性的檢測結(jié)果時，應(yīng)該如何正確看待呢？不要過于緊張或恐慌。ANA陽性并不一定意味著患有結(jié)締組織病或其他自身免疫性疾病。我們需要結(jié)合患者的臨床癥狀、其他實(shí)驗(yàn)室檢查結(jié)果以及影像學(xué)檢查等來進(jìn)行綜合評估。如果ANA陽性且伴有明顯的臨床癥狀或其他實(shí)驗(yàn)室指標(biāo)異常，那么就需要及時就醫(yī)并尋求專業(yè)醫(yī)生的幫助。醫(yī)生會根據(jù)患者的具體情況進(jìn)行進(jìn)一步的檢查和診斷，并制定相應(yīng)的治療方案。即使ANA陽性被確診為某種自身免疫性疾病，也不必過于擔(dān)心。隨著現(xiàn)代醫(yī)學(xué)的不斷進(jìn)步和發(fā)展，許多自身免疫性疾病都可以得到有效的治療和控制。只要我們積極配合醫(yī)生的治療和建議，保持良好的生活習(xí)慣和心態(tài)，就能夠戰(zhàn)勝疾病并恢復(fù)健康。寫在最后抗核抗體作為風(fēng)濕免疫科的一項(xiàng)重要篩查指標(biāo)，其陽性結(jié)果并不等同于結(jié)締組織病或其他自身免疫性疾病。我們需要結(jié)合患者的具體情況進(jìn)行綜合評估，并及時就醫(yī)并尋求專業(yè)醫(yī)生的幫助。
埃勒斯-當(dāng)洛斯Ehlers-Danlos綜合征的綜述（2020）埃勒斯-當(dāng)洛斯Ehlers-Danlos綜合征的綜述（2020）AreviewofEhlers-Danlossyndrome?MillerE,GroselJM.AreviewofEhlers-Danlossyndrome[J].JAAPA,2020,33(4):23-28.轉(zhuǎn)載文章的原鏈接1：https://pubmed.ncbi.nlm.nih.gov/32175940/轉(zhuǎn)載文章的原鏈接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綜合征（EDS）描述了一組遺傳性結(jié)締組織疾病，包括參與膠原結(jié)構(gòu)和/或生物合成的基因突變?，F(xiàn)已確認(rèn)的EDS亞型有13種，各亞型之間以及與其他結(jié)締組織疾病的癥狀有很大程度的重疊。EDS的臨床特征是組織脆弱，關(guān)節(jié)過度活動和皮膚過度伸展。EDS的正確診斷對于正確的多學(xué)科治療非常重要，并且與患者更好的臨床結(jié)果相關(guān)。?Keywords:Ehlers-Danlossyndrome,connectivetissuedisease,jointhypermobility關(guān)節(jié)過度活動,tissuefragility,skinhyperextensibility皮膚伸展過度,heritabledisease?LearningobjectivesDescribetheclinicalpresentationofEDS.UnderstandthepotentialcomplicationsandappropriatemanagementofEDS.描述EDS的臨床表現(xiàn)。了解EDS的潛在并發(fā)癥和適當(dāng)?shù)奶幚矸椒ā?KeypointsEDSdescribesagroupofheritabledisordersofconnectivetissue.ThirteenEDSsubtypesarerecognized,withawidedegreeofsymptomoverlapamongsubtypesandwithotherconnectivetissuedisorders.TheclinicalhallmarksofEDSaretissuefragility,jointhypermobility,andskinhyperextensibility.PatientswithEDSaremanagedsymptomaticallybecausetheconditionhasnoknowncure.EDS描述了一組遺傳性結(jié)締組織疾病。現(xiàn)已確認(rèn)的EDS亞型有13種，各亞型之間以及與其他結(jié)締組織疾病的癥狀有很大程度的重疊。EDS的臨床特征是組織脆弱，關(guān)節(jié)過度活動和皮膚過度伸展。EDS患者需要對癥治療，因?yàn)檫@種疾病沒有已知的治愈方法。?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髕骨軌跡綜合征.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膠原蛋白的生物合成或結(jié)構(gòu).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:根據(jù)2017年《國際埃勒-丹洛斯綜合征分類》，EDS的13種臨床亞型是: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分子檢測.?GENETICANDPATHOGENETICMECHANISMSInadditiontotheupdatedclinicalclassificationsystem,the2017InternationalClassificationoftheEhlers-DanlosSyndromesalsoproposedageneticclassificationsystem遺傳學(xué)分類系統(tǒng).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的遺傳機(jī)制尚不清楚，因此未被列入這些類群。?INHERITANCEPATTERNSAllsubtypesofEDSexcepthEDShaveaknowngeneticbasis.EDScanbeinheritedinanautosomaldominantorrecessivemanner,orcanoccurasanovelgeneticmutation.2除hEDS外，所有EDS亞型都有已知的遺傳基礎(chǔ)。EDS可以常染色體顯性遺傳或隱性遺傳，也可以作為一種新的基因突變發(fā)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組織脆弱的癥狀在EDS患者中很常見，并且可以通過多種方式表現(xiàn)出來。組織脆弱的輕微表現(xiàn)可能包括傷口愈合不良、疤痕營養(yǎng)不良和容易擦傷更嚴(yán)重甚至危及生命的組織脆弱表現(xiàn)可引起胃腸道出血、腦血管或顱內(nèi)出血、動脈瘤形成和破裂。?JointhypermobilityThisdescriptivetermisusedtodescribeajointthathasanincreasedrangeofmotioncomparedwithanormaljoint.Generalizedjointhypermobilitymayindicatealargerunderlyingpathology.Inpatientswithgeneralizedjointhypermobility,affectedjointsaretypicallypresentinthefourlimbsandaxialskeleton.WhenconsideringadiagnosisofEDS,cliniciansmustdifferentiatebetweenasinglehypermobilejointandgeneralizedjointhypermobility.2,9Severalmethodscanbeusedtoassessgeneralizedjointhypermobility;themostcommonmethodinvolvescalculatingtheBeightonscore(Table1).9-12這個描述性術(shù)語用于描述與正常關(guān)節(jié)相比活動范圍增加的關(guān)節(jié)。全身性關(guān)節(jié)過度活動可能表明更大的潛在病理。在全身性關(guān)節(jié)活動過度的患者中，受影響的關(guān)節(jié)通常存在于四肢和軸骨。當(dāng)考慮EDS的診斷時，臨床醫(yī)生必須區(qū)分單一關(guān)節(jié)過度活動和廣泛性關(guān)節(jié)過度活動2,9。有幾種方法可用于評估廣泛性關(guān)節(jié)過度活動;最常用的方法是計算貝頓分?jǐn)?shù)(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通過拉皮膚和皮下皮膚層來評估皮膚的延展性，直到感覺到阻力。皮膚應(yīng)該很容易伸展，釋放后應(yīng)該彈回原位。測試應(yīng)在不太可能遭受機(jī)械創(chuàng)傷或疤痕的區(qū)域進(jìn)行。Skinshouldbeconsideredhyperextensibleifitcanbestretchedexcessivelyinatleastthreeoftheselocations:distalforearms,dorsumofthehands,neck,elbows,orknees.2Iftheskinofthedistalforearmsanddorsumofthehandscanbestretchedatleast1.5cm,orskinoftheneck,elbow,andkneesstretchedatleast3cm,itisconsideredhyperextensible(Figure3).2如果皮膚在前臂遠(yuǎn)端、手背、頸部、肘部或膝蓋至少三個部位可以過度拉伸，則應(yīng)考慮皮膚過度拉伸。如果前臂遠(yuǎn)端和手背的皮膚可拉伸至少1.5cm，或頸部、肘部和膝蓋的皮膚可拉伸至少3cm，則認(rèn)為是超可伸性(圖3)。??FIGURE3.:Thecasepatientdemonstratinghyperextensibilityofherskinatherelbow(A)andknee(B).??DIAGNOSISDiagnosingEDSisconsideredcomplexforseveralreasons.5,13,14Medicalprofessionals'trainingoftendoesnotincludeacomprehensiveeducationonthediagnosisandmanagementofEDS.15Furthermore,manysignsandsymptomsmaybesubtle,andthusmaynotreadilyalertclinicianstothepossibilityofanunderlyingpathology.13FeaturesofEDSoftenoverlapwithsymptomsofotherconnectivetissuedisorders,suchasjointhypermobilitysyndrome關(guān)節(jié)過度活動綜合征,Marfansyndrome馬凡綜合征,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患者的治療是對癥的，因?yàn)檫@種病沒有已知的治愈方法。然而，目前還沒有針對EDS患者的管理指南，而且不同患者的治療方法也有很大差異，通過全面的病史和體格檢查記錄病人的癥狀，然后轉(zhuǎn)診給適當(dāng)?shù)膶？漆t(yī)生。由于EDS通常涉及多個器官系統(tǒng)，因此管理通常需要來自多個專業(yè)的醫(yī)療保健提供者之間的協(xié)作努力。Patienteducationisanimportantcomponentofdiseasemanagement,andmayinvolvewaystopreventunwantedjointevents,suchasdislocation.17Ahealthfullifestylecanhelppatientsstrengthenjoints,preventjointinjury,andcanhelppreventincreasedjointpainlaterinlife.Inaddition,physicaltherapyandoccupationaltherapymaybebeneficial.19患者教育是疾病管理的一個重要組成部分，可能包括預(yù)防不希望發(fā)生的聯(lián)合事件，如脫位的方法健康的生活方式可以幫助患者加強(qiáng)關(guān)節(jié)，防止關(guān)節(jié)損傷，并有助于防止晚年關(guān)節(jié)疼痛加劇。此外，物理治療和職業(yè)治療可能是有益的。SeveralstudieshaveshownanassociationamongEDS,psychologicaldistress,andreducedqualityoflife.5,20Manypatientsaresusceptibletoanxiety,depression,disability,andsocialisolation.15,17PatientsdiagnosedwithEDSmayneedpsychologicalsupport,andearlyinterventionmayleadtobetterclinicaloutcomes.16一些研究表明EDS、心理困擾和生活質(zhì)量下降之間存在關(guān)聯(lián)5,20。許多患者易患焦慮、抑郁、殘疾和社會孤立15,17。診斷為EDS的患者可能需要心理支持，早期干預(yù)可能導(dǎo)致更好的臨床結(jié)果。?SurgeryandotherproceduresPatientswithEDSmayhavecomplicationsduringroutinemedicalprocedures,surgery,andtheperioperativeperiod.Forexample,onestudyshowedthatpatientswithvEDSarehighlysusceptibletosurgicalcomplicationssuchasseverebleedingandcomplicationsofanesthesia.PatientswithEDSshouldobtainpreoperativeclearancebeforeundergoingsurgery.Cliniciansmayconsidersendingthesepatientstoaspecializedpreoperativeevaluationcenterforclearance.6EDS患者可能在常規(guī)醫(yī)療程序、手術(shù)和圍手術(shù)期出現(xiàn)并發(fā)癥。例如，一項(xiàng)研究表明，vEDS患者極易出現(xiàn)手術(shù)并發(fā)癥，如大出血和麻醉并發(fā)癥。EDS患者應(yīng)在手術(shù)前獲得術(shù)前清除。臨床醫(yī)生可能會考慮將這些患者送到專門的術(shù)前評估中心進(jìn)行檢查。?ObstetricconsiderationsConsiderreferraltoanobstetricianwhohandleshigh-riskpregnanciesforallpregnantpatientswithEDS,becausecomplicationssuchasprematureruptureofmembranes,uterinehemorrhage,oruterinerupturecanoccurduringpregnancyanddelivery.13,18考慮轉(zhuǎn)診到產(chǎn)科醫(yī)生處理高危妊娠的所有妊娠EDS患者，因?yàn)椴l(fā)癥，如膜早破，子宮出血，或子宮破裂可能發(fā)生在懷孕和分娩期間。?CardiovascularproblemsEDSisassociatedwithanincreasedincidenceofcardiovascularabnormalities,suchasmitralvalveprolapseandaorticdissection.13AlthoughstandardizedguidelinesarelackingforevaluatingcardiovascularabnormalitiesinpatientswithEDS,baselineechocardiogramsoftenareobtainedatthetimeofdiagnosis.13Aorticdiametermeasurementalsoisrecommended,andmayrequireadditionalevaluationwithCTorMRIangiographyifvisibilityonechocardiogramislimited.7,13ReferraltoacardiologistofteniswarrantedforpatientswithEDS.16,19EDS與心血管異常的發(fā)生率增加有關(guān)，如二尖瓣脫垂和主動脈夾層雖然缺乏標(biāo)準(zhǔn)化的指南來評估EDS患者的心血管異常，但在診斷時通常可以獲得基線超聲心動圖主動脈直徑測量也是推薦的，如果超聲心動圖上的可見性有限，可能需要額外的CT或MRI血管造影評估7,13。對于EDS患者，轉(zhuǎn)診給心臟病專家通常是有保證的。?ChronicpainThisisoneofthemostcommoncomplaintsinpatientswithEDS,andcanimpairpatients'schoolandworklives,personalrelationships,andpsychologicalwell-being.TreatingpaininpatientswithEDScanbechallengingandmayrequirereferraltoapainspecialist.21-23Managementtypicallyinvolvesamultimodalapproach,usingsuchmethodsasphysical,occupationalandcognitivebehavioraltherapies,pharmacologicagents,splintingofunstablejoints,compressiongarments,shoeinserts,andspecializedexerciseprograms.22,23這是EDS患者最常見的主訴之一，并且會損害患者的學(xué)習(xí)和工作生活、人際關(guān)系和心理健康。治療EDS患者的疼痛是具有挑戰(zhàn)性的，可能需要轉(zhuǎn)介到疼痛專家21-23。典型的治療包括多模式的方法，使用諸如物理、職業(yè)和認(rèn)知行為療法、藥物、不穩(wěn)定關(guān)節(jié)夾板、壓縮服裝、鞋墊和專門的鍛煉計劃等方法。Opioidsmaybeusefulinthesepatients,butshouldbeusedwithcaution.Onestudyfoundthat,comparedwithage-matchedcontrols,patientswithEDSareprescribedopioidsmorefrequentlyandathigherdosesthanpatientswhodonothaveEDS.Chronicopioidusecanleadtotoleranceandanincreasedriskfordependence.21阿片類藥物可能對這些患者有用，但應(yīng)謹(jǐn)慎使用。一項(xiàng)研究發(fā)現(xiàn)，與年齡匹配的對照組相比，EDS患者比沒有EDS的患者更頻繁地服用阿片類藥物，劑量也更高。長期使用阿片類藥物可導(dǎo)致耐受性和依賴性風(fēng)險增加。?CONCLUSIONEDSisacomplexdiseasecausedbymutationsingenesinvolvedinthestructureandbiosynthesisofcollagen.ThenewestEDSclassificationsystemcanserveasadiagnosticframeworkforclinicalevaluationofpatientswithsuspectedEDS.Thediagnosisshouldbeconfirmedwiththeappropriategenetictesting.Promptrecognition,diagnosis,andinitiationoftreatmentinpatientswithEDSareassociatedwithbetterclinicaloutcomesandqualityoflife.AlthoughanupdatedsystemfordiagnosingthesubtypesofEDShasbeenestablished,nostandardcriteriaexistformanagingthesyndrome;referraltomultiplemedicalspecialiststypicallyisrequired.EDS是一種復(fù)雜的疾病，由參與膠原結(jié)構(gòu)和生物合成的基因突變引起。最新的EDS分類系統(tǒng)可作為臨床評估疑似EDS患者的診斷框架。診斷應(yīng)通過適當(dāng)?shù)幕驒z測來證實(shí)。EDS患者的及時識別、診斷和開始治療與更好的臨床結(jié)果和生活質(zhì)量相關(guān)。雖然已經(jīng)建立了診斷EDS亞型的最新系統(tǒng)，但沒有管理該綜合征的標(biāo)準(zhǔn)準(zhǔn)則;通常需要轉(zhuǎn)介給多名醫(yī)學(xué)專家。