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方洪元
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醫(yī)生集團(tuán)-天津? 線上診療科
擅長:結(jié)締組織疾病、大皰性疾病、銀屑病,性病及疑難皮膚病的診斷與治療。我市疑難皮膚病首席會診專家。
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皮膚性病科
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什么是非典型結(jié)締組織?。?/a>
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?;蜉p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(xiǎn)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!
石麗雅醫(yī)生的科普號
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?,如寄生蟲感染、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。腫瘤性疾病:某些腫瘤性疾病,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。
盛景祖醫(yī)生的科普號
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?,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(jì)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??梢垣@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(jì)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(xiǎn)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。
曾紀(jì)洲醫(yī)生的科普號