結(jié)締組織病肺間質(zhì)病變?cè)\治進(jìn)展-張煊

結(jié)締組織病肺間質(zhì)病變?cè)\治進(jìn)展北京協(xié)和醫(yī)院風(fēng)濕免疫科張烜間質(zhì)性肺病（interstitiallungdisease，ILD）CTD的常見(jiàn)疾病可以是CTD的首發(fā)癥狀是預(yù)后不良的原因之一是肺動(dòng)脈高壓(PAH）的原因之一影響肺功能呼吸肌受累反復(fù)誤吸(食道功能)血栓栓塞

頸部軟骨炎癥

支氣管擴(kuò)張ILD的發(fā)生率15%的CTD合并ILD70%SSc合并肺部病變，2年內(nèi)可發(fā)展為ILD，組織病理77.5%SSc伴ILD10%DM/PM合并ILD胸片顯示3.7%RA合并ILDSLE，SS，MCTDClinChestMed2004;25:549~559AmJRespirCritCareMed2002;165:1581~6AnnRheumDis2003;62:897~900CTD中的ILD發(fā)生率、嚴(yán)重度及病死率的比較1）CTD中ILD的特點(diǎn)注：1）指5年之內(nèi)因呼吸衰竭死亡2）國(guó)外無(wú)對(duì)比數(shù)據(jù)3）均為DM患者張烜,董怡,張奉春.中華風(fēng)濕病學(xué)雜志,1999;3:247分型的目的自然病程、對(duì)激素反應(yīng)、預(yù)后CTD-UIP是否等同特發(fā)UIP?SSc-ILD-ACR2006報(bào)道美國(guó)Denver

FischerA對(duì)27例肺活檢的SSc患者（14例NSIP，8例UIP）分析表明：盡管都予同樣的激素和免疫抑制劑治療，SSc-NSIP中位生存時(shí)間為15.3年，而UIP為3年。ILD病理和影像學(xué)特點(diǎn)ILD的分類(lèi)易發(fā)生的疾病非特異性間質(zhì)性肺炎（NIP）SScPM/DMRASLESSMCTD尋常型間質(zhì)性肺炎（UIP）RASScPM/DMSS機(jī)化型肺炎（OP）PM/DMRASScSLESS淋巴細(xì)胞浸潤(rùn)性肺炎（LIP）SSSLERAMCTD脫屑性間質(zhì)性肺炎（DIP）SLERASSc彌漫性肺泡炎（DAD）SLESScPM/DMRAMCTDCurrOpinRheumtol2004;16:186~191HRCT-NSIPSScDM/PMHRCT-UIPSScRADM/PMUIP-HRCT特點(diǎn)病變不均勻下肺為主牽拉性支氣管擴(kuò)張無(wú)明顯毛玻璃變HRCT–慢性LIPSSRA藥物HRCTobliterativebronchiolitisRASLESclerodermaPM/DMHRCTorganizingpneumoniaGoldSSZMTXSjogren’ssyndromRAHRCTapatientwithRA33%ofwithRAassociatedparenchymallungdisease31IPFRadiography:2-6%29HRCT:10%-47%35-8HRCT:50%withbroncioectasesandbronchiolectasisSLE-Chronicinterstitialpneumonia

Radiographic-6–24%HRCT–24/34abnormal 11/34CIPFenlonHM,DoranM,SantSM,etal.AmJRoentgenol1996;166:301–7.EstesD,ChristianCL.Medicine(Baltimore)1971;50:85–95.Raynaud’sphenomenon,swollenfingers,sclerodactyly,telangiectasia,dyspnoea,nailfoldcapillaryabnormalitiesMaybeefficacious:CorticosteroidsImmunosuppressiveagents與ILD的相關(guān)因素與病種有關(guān)在RA中與RF的滴度有關(guān)DM/PM與抗Jo-1抗體有關(guān)抗RNP抗體ClinExpAllergy2003;33:226~232ArthritisRheum2002;47:614~622預(yù)后病理分型CTDSSc-ILD預(yù)后

病理

起病時(shí)嚴(yán)重程度

血漿HcY

合并肺高壓BAL細(xì)胞？

TGFbeta,MMPSSc-ILD其它標(biāo)志物呼出NO測(cè)定：內(nèi)皮血清SP-D(A)/KL-6：肺泡II型上皮細(xì)胞治療ILD治療的中心問(wèn)題是GC和免疫抑制的指征GC是最常用藥，眾多病人無(wú)反應(yīng)預(yù)后取決于分型GC+CTX療效好于單用GCAmJRespirCritCareMed1996;154:400ArthritisRheum1994;37:1290SeminArthritisRheum2003;32:273治療ILD治療的中心問(wèn)題是GC和免疫抑制的指征GC是最常用藥，眾多病人無(wú)反應(yīng)預(yù)后取決于分型GC+CTX療效好于單用GCAmJRespirCritCareMed1996;154:400ArthritisRheum1994;37:1290SeminArthritisRheum2003;32:273PM/DM-ILD病理類(lèi)型與治療無(wú)肌病性皮肌炎者有更高幾率發(fā)生DAD；可呈爆發(fā)式發(fā)展，可在數(shù)月內(nèi)致死。需要積極加用足量環(huán)磷酰胺或環(huán)孢素以及激素治療抗CADM抗體（anti-clinicallyamyopathicdermatomyositisantibodies）預(yù)示快速進(jìn)展ILDRecentadvancesinthetreatmentofinterstitiallungdiseaseinpatientswithpolymyositis/dermatomyositis.EndocrMetabImmuneDisordDrugTargets.2006Dec;6(4):409-15.足量激素1mg/kg/day聯(lián)用大劑量環(huán)孢A（需用200mg/day），并在診斷后15天內(nèi)開(kāi)始使用，可有效降低DM-A/SIP的死亡率。足量激素與免疫抑制劑在初始階段即同時(shí)使用要明顯優(yōu)于單用激素控制不佳后再加用環(huán)孢A的治療效果EarlyinterventionwithcorticosteroidsandcyclosporinAand2-hourpostdosebloodconcentrationmonitoringimprovestheprognosisofacute/subacuteinterstitialpneumoniaindermatomyositis.

JRheumatol.2008Feb;35(2):254-9.Epub2007Dec15

Step-upversusprimaryintensiveapproachtothetreatmentofinterstitialpneumoniaassociatedwithdermatomyositis/polymyositis:aretrospectivestudy，ModRheumatol.2007;17(2):123-30.Epub2007Apr20.

治療RA-ILDCTX,環(huán)孢素,AZA,羥基氯喹thefirstpositiveresultsofaPCT治療SSc-ILD-NEJM報(bào)道DBRPCT美國(guó)13個(gè)中心，158例患者口服CTX或安慰劑１年，隨訪２年P(guān)EP--FVC治療SSc-ILD-NEJM報(bào)道Of158patients,145completedatleastsixmonthsoftreatmentandwereincludedintheanalysis.Themeanabsolutedifferenceinadjusted12-monthFVC%predicted

betweentheCTXandplacebogroupswas2.53%(95%CI0.28to4.79%),favoringCTX(P<0.03).治療SSc-ILD-NEJM報(bào)道Therewerealsotreatment-relateddifferencesinphysiologicalandsymptomoutcomes,

andthedifferenceinFVCwasmaintainedat24months.Therewasagreater

frequencyofadverseeventsintheCTXgroup,butthedifferencenotsignificant.治療SSc-ILD-NEJM報(bào)道在治療１年時(shí)，HRCT纖維化嚴(yán)重病人在安慰劑組FVC下降明顯，而在CTX組纖維化對(duì)FVC影響不明顯(P=0.009)對(duì)SSc中已有纖維化說(shuō)明存在相對(duì)早期活動(dòng)性肺泡炎，如不治療，病情容易進(jìn)展。治療SSc-ILD-NEJM結(jié)論OneyearoforalCTXinsymptomaticSSc-ILDhadasignificantbutmodestbeneficialeffectonlungfunction,dyspnea,thickeningoftheskin,andthehealth-relatedqualityoflife.Theeffectsonlungfunctionwere

maintainedthroughthe24msofthestudy.治療SSc-ILD-NEJM問(wèn)題DLco差別無(wú)顯著意義治療ILD－排除感染

PCP感染

SLE,myositis,WG—長(zhǎng)期激素，MTX,TNFa抑制劑

治療ILD－排除感染CMV感染左下肺T結(jié)節(jié)影，TB05-11-23雙下肺滲出影05-12-7經(jīng)靜脈大扶康治療2周后，滲出明顯吸收06-3-1右肺滲出影06-4-3予口服伊曲康唑1月后,右肺滲出影吸收治療ILD－MTX?急性超敏性肺泡炎及慢性肺纖維化誘發(fā)PCP感染

ILD盡量不用MTX小劑量MTX？治療－IPF啟示治療－IPF啟示Thesynthesisofglutathionecanbeacceleratedbythe

administrationofNAC,whichcrossescellmembranes

easilyandcanbeconvertedtol-cysteine.Uptakeofl-cysteineisanimportantrate-limitingstepforthesynthesis

ofglutathione.NACincreasesthepoolofotherantioxidantthiolsthatalsoprotectcellsfrominjury.182例(92NAC，90安慰劑).155例(80NACand75安慰劑)UIPHRCT和病理診斷57/80NAC(71%)and51/75takingplacebo(68%)completedoneyearoftreatment.NACslowedthedeteriorationofVCandDlcoat12months,absolutedifferencesinthechangefrombaselinebetweenpatientstakingNACandthosetakingplacebowere0.18liter(95%CI,0.03to0.32),relativedifferenceof9%,forVC(P=0.02),and0.75mmolperminuteperkilopascal(95%CI,0.27to1.23),or24%,forDlco(P=0.003).Mortalityduringthestudywas9%NACand11%placebo(P=0.69).TherewerenosignificantdifferencesinthetypeorseverityofadverseeventsbetweenpatientstakingNACandthosetakingplacebo,exceptforasignificantlylowerrateofmyelotoxiceffectsinthegrouptakingNAC(P=0.03).生物靶向治療——效果尚不明確α-TNF靶向治療

薈萃分析表明：有233例RA、SLE等疾病的患者使用α-TNF靶向治療后繼發(fā)了皮膚血管炎、ILD等，其中24例發(fā)生了ILD，即使停藥后預(yù)后仍較差，部分可能與MTX聯(lián)用有關(guān)。AutoimmunediseasesinducedbyTNF-targetedtherapies:analysisof233cases.Medicine(Baltimore).2007Jul;86(4):242-51.

有病例報(bào)道etanercept

的治療使原有ILD的RA患者的肺部病變急性加重Acuteexacerbationofpreexistinginterstitiallungdiseaseafteradministrationofetanerceptforrheumatoidarthritis.JRheumatol.2007May;34(5):1151-4.Epub2007Apr15.

但也有報(bào)道稱未發(fā)現(xiàn)Infliximab、etanercept