安徽省醫學會重癥醫學分會第十二次年會認識免疫重建炎癥綜合征安徽醫科大學第二附屬醫院孫昀金2019.10.31安徽省醫學會重癥醫學分會第十二次年會1CaseReportA35-year-oldmalewithan8-yearhistoryofAIDSpresentedwitha3dayhistoryofrecurrentfrontalheadaches,subjectivefeverandalteredmentalstatusHehadahistoryofnon-adherencetomedicationsbuthehadresumedantiretroviraldrugsforabout10weeksFourweekspriortopresentationtoourhospital,hehadbeendiagnosedwithcryptococcalmeningitis(CM)inanoutsidehospitalandhadreceiveda7daycourseofintravenousamphotericinB(lipidcomplexpreparationThiswasdiscontinuedduetoprogressiveacutekidneyinjuryandhewassubsequentlyplacedonhighdose(800mgoralfluconazole(flu)dailyInfectiousDiseaseReports2019volume6:5576CaseReport2CaseReportFigure1.Braiaxialandcoronalviewsshysticstructureswithinthelateralventriclesperiventricularwhitematterareaandbasalglia.Thereisenlargementoftheventricularsystemaswell.B)showsadditionalcysticlesionssurroundingthefourthventricle.InfectiousDiseaseReports2019;volume6:5576CaseReport3CaseReportHewasreadmittedtothehospital5weekslaterwithrecurrentheadachesandfeversMRiofhisbrainshowednochangeTable1.TrendofCD4countandHIVviralload8weekspriortoinitialpresentation,aswellascerebrospinalfluidparametersandantifungalinductiontreatmentcoursesoftheindexpatientduringthefirst5monthsofhispresentationWeek-8Week1Week12Week4Week6Week20CSFCRAG>1024>1:10241:18>11024CSFopeningpressureNRNCSFWBC(lymphs)24(840)14(92%)2366%protetI+veastCSFculturec1growthNogrowthNogrowth物燦gohHIVVL(copies/mL)50.001740detected<20CD4count(cellspL)9(nadir16AntifungalinductiontherapyAmB(Iweek)LAmWeeklrisitwasataseparatehospitalCSf,cerehrospnalluid,CRA,Cryptococcalantigen;NR,notreported,WBC,whilebloodcels,VL,vIalload,AmB,anpboteriinBdeoxycholateLAmB,IipusonaamphoteritinB:5-FCfcyasine.Thepatietwashospitalisedonweeks1,5,[.InfectiousDiseaseReports2019;volume6:5576CaseReport4發現HIVinfectionischaracterizedbyagradualreductioninthecountsofCD4+lymphocytesopportunisticinfections(oI)andspecificneoplasticprocesseshighlyactiveantiretroviraltherapy(HaartdecreaseinviralloadimprovementinCD4+TcellcountsreducestheOiandprolongedalsurvIv:fewpatientsexperienceaclinicaldeteriorationduetodysbalancedrestorationoftheCD4TcelloftheimmunesystemJournalofTnternationalOralHealth2019;7(4):92-95發現5命名起初免疫修復疾病(imunereeonstitutiodisease,IRD)免疫重建病(immunereconstitutionsyndrome,IRS)ftal2019npatientwthpeniseshistoryofirsetien,raine鑒于宿主的炎性反應在發病中的重要作用opoortrensiepousinDesimone等首次提出免疫重建炎性綜合征。國(immunereconstitutioninflammationsyndromeIRIS命名6臨床表現根據涉及的感染性或非感染性因子的不同而不同分枝桿菌引起的淋巴結病、結核病的異常表現>進展性多灶性腦白質病的惡化耶氏肺孢子菌肺炎弓形蟲病的復發巨細胞病毒性視網膜炎病毒性肝炎>有些則可能表現為自身免疫性疾病Riswhichmaymanifestasanewlyidentifiedopportunisticinfection(ol)inouslyasymptomaticindividuals(unmaskingIRiS)orwithparadoclinicalworseningofaknownol(paradoxicalIRIS)臨床表現根據涉及的感染性或非感染性因子的不同而不同7IRIS的危害部分患者不能耐受現有的治療或對ART藥物的作用產生懷疑自行停止ART服藥的依從性降低,導致誘發HV耐藥變異的產生與傳播,影響ART的遠期治療效果和未來治療的選擇增加住院率,降低患者生活質量,提高艾滋病防治工作成本;IRS的表現常被誤判為抗OI病原體治療無效所引起的一系列表現,導致對其治療方案的不適當調整。少數患者因IRIS死亡;影響患者的遠期免疫功能重建,研究表明部分發生IRIS的患者,ART3-4年后CD細胞的恢復仍受到景響。MedmycolCaseRep:2019:5:16-9IRIS的危害8IRIS的發病率艾滋病患者在接受ART后6個月內IRS的發病率歐美發達國家為10%~15%資源有限的發展中國家為20%~25%絕大多數發生于治療的前3個月JpnJldeaDis,2019,61:205A|DS,2019,601-10IRIS的發病率9IRIS的發病機制體液免疫相關的輔助性T細胞在介導機體與外源性抗原的免疫反應中起重要作用。同源性配體激發Th0細胞初始CD4T細胞)在不同細胞因子的作用下進行分化Th1細胞能分洶γ干擾素(interferonγ,IFN-),引起前炎癥反應。Th2細胞能分泌抗炎和免疫抑制性細胞因子如lnterleukin10,IL-Th3胞能分泌轉化生長因子β(transforminggrowthfactorβ,TGF-βTh2細胞能抑制Th1細胞的轉化甘如陽T輔助細胞一個正常功能的免疫系統是基于Th免疫應答「輔助體液免疫應答IRIS的發病機制10認識免疫重建炎癥綜合征課件講義11認識免疫重建炎癥綜合征課件講義12認識免疫重建炎癥綜合征課件講義13認識免疫重建炎癥綜合征課件講義14認識免疫重建炎癥綜合征課件講義15認識免疫重建炎癥綜合征課件講義16認識免疫重建炎癥綜合征課件講義17認識免疫重建炎癥綜合征課件講義18認識免疫重建炎癥綜合征課件講義19認識免疫重建炎癥綜合征課件講義20認識免疫重建炎癥綜合征課件講義21認識免疫重建炎癥綜合征課件講義22認識免疫重建炎癥綜合征課件講義23認識免疫重建炎癥綜合征課件講義24認識免疫重建炎癥綜合征課件講義25認識免疫重建炎癥綜合征課件講義26認識免疫重建炎癥綜合征課件講義27認識免疫重建炎癥綜合征課件講義28認識免疫重建炎癥綜合征課件講義29認識免疫重建炎癥綜合征課件講義30認識免疫重建炎癥綜合征課件講義31安徽省醫學會重癥醫學分會第十二次年會認識免疫重建炎癥綜合征安徽醫科大學第二附屬醫院孫昀金2019.10.31安徽省醫學會重癥醫學分會第十二次年會32CaseReportA35-year-oldmalewithan8-yearhistoryofAIDSpresentedwitha3dayhistoryofrecurrentfrontalheadaches,subjectivefeverandalteredmentalstatusHehadahistoryofnon-adherencetomedicationsbuthehadresumedantiretroviraldrugsforabout10weeksFourweekspriortopresentationtoourhospital,hehadbeendiagnosedwithcryptococcalmeningitis(CM)inanoutsidehospitalandhadreceiveda7daycourseofintravenousamphotericinB(lipidcomplexpreparationThiswasdiscontinuedduetoprogressiveacutekidneyinjuryandhewassubsequentlyplacedonhighdose(800mgoralfluconazole(flu)dailyInfectiousDiseaseReports2019volume6:5576CaseReport33CaseReportFigure1.Braiaxialandcoronalviewsshysticstructureswithinthelateralventriclesperiventricularwhitematterareaandbasalglia.Thereisenlargementoftheventricularsystemaswell.B)showsadditionalcysticlesionssurroundingthefourthventricle.InfectiousDiseaseReports2019;volume6:5576CaseReport34CaseReportHewasreadmittedtothehospital5weekslaterwithrecurrentheadachesandfeversMRiofhisbrainshowednochangeTable1.TrendofCD4countandHIVviralload8weekspriortoinitialpresentation,aswellascerebrospinalfluidparametersandantifungalinductiontreatmentcoursesoftheindexpatientduringthefirst5monthsofhispresentationWeek-8Week1Week12Week4Week6Week20CSFCRAG>1024>1:10241:18>11024CSFopeningpressureNRNCSFWBC(lymphs)24(840)14(92%)2366%protetI+veastCSFculturec1growthNogrowthNogrowth物燦gohHIVVL(copies/mL)50.001740detected<20CD4count(cellspL)9(nadir16AntifungalinductiontherapyAmB(Iweek)LAmWeeklrisitwasataseparatehospitalCSf,cerehrospnalluid,CRA,Cryptococcalantigen;NR,notreported,WBC,whilebloodcels,VL,vIalload,AmB,anpboteriinBdeoxycholateLAmB,IipusonaamphoteritinB:5-FCfcyasine.Thepatietwashospitalisedonweeks1,5,[.InfectiousDiseaseReports2019;volume6:5576CaseReport35發現HIVinfectionischaracterizedbyagradualreductioninthecountsofCD4+lymphocytesopportunisticinfections(oI)andspecificneoplasticprocesseshighlyactiveantiretroviraltherapy(HaartdecreaseinviralloadimprovementinCD4+TcellcountsreducestheOiandprolongedalsurvIv:fewpatientsexperienceaclinicaldeteriorationduetodysbalancedrestorationoftheCD4TcelloftheimmunesystemJournalofTnternationalOralHealth2019;7(4):92-95發現36命名起初免疫修復疾病(imunereeonstitutiodisease,IRD)免疫重建病(immunereconstitutionsyndrome,IRS)ftal2019npatientwthpeniseshistoryofirsetien,raine鑒于宿主的炎性反應在發病中的重要作用opoortrensiepousinDesimone等首次提出免疫重建炎性綜合征。國(immunereconstitutioninflammationsyndromeIRIS命名37臨床表現根據涉及的感染性或非感染性因子的不同而不同分枝桿菌引起的淋巴結病、結核病的異常表現>進展性多灶性腦白質病的惡化耶氏肺孢子菌肺炎弓形蟲病的復發巨細胞病毒性視網膜炎病毒性肝炎>有些則可能表現為自身免疫性疾病Riswhichmaymanifestasanewlyidentifiedopportunisticinfection(ol)inouslyasymptomaticindividuals(unmaskingIRiS)orwithparadoclinicalworseningofaknownol(paradoxicalIRIS)臨床表現根據涉及的感染性或非感染性因子的不同而不同38IRIS的危害部分患者不能耐受現有的治療或對ART藥物的作用產生懷疑自行停止ART服藥的依從性降低,導致誘發HV耐藥變異的產生與傳播,影響ART的遠期治療效果和未來治療的選擇增加住院率,降低患者生活質量,提高艾滋病防治工作成本;IRS的表現常被誤判為抗OI病原體治療無效所引起的一系列表現,導致對其治療方案的不適當調整。少數患者因IRIS死亡;影響患者的遠期免疫功能重建,研究表明部分發生IRIS的患者,ART3-4年后CD細胞的恢復仍受到景響。Medmycol