肺隱球菌病.ppt

肺隱球菌病 PC pulmonarycryptococcosis 從一個(gè)病例談起 復(fù)旦大學(xué)附屬華山醫(yī)院北院呼吸科張有志 病史介紹 患者 女性 47歲主述 因 反復(fù)咳嗽伴胸痛1月 入院 B院 現(xiàn)病史 患者于2010 9 5無(wú)明顯誘因出現(xiàn)咳嗽 少量白痰 伴右側(cè)胸痛 陣發(fā)性鈍痛 深吸氣時(shí)明顯 無(wú)放射痛 無(wú)發(fā)熱 無(wú)嘔吐 頭痛 某A院行胸部CT示 右下肺炎 予以莫西沙星靜滴8天患者咳嗽 胸痛有所緩解 繼續(xù)口服莫西沙星6天 2010 9 27復(fù)查CT無(wú)吸收 于2010 10 12就診B院 既往 體健 否認(rèn)性病冶游史 家中曾養(yǎng)寵物 鴿子 狗 查體 T 37 9 淺表淋巴結(jié)不大 右下肺可及濕啰音 輔助檢查 血常規(guī) 肝腎功能 D 二聚體正常 ESR 65mm h CRP 48mg L 血?dú)夥治稣?HIV PPD試驗(yàn)陰性 LA試驗(yàn) G試驗(yàn)陰性 送至C院檢測(cè) 2010 9 6A院CT 2010 9 27A院CT 病史介紹 A院氣管鏡檢查 鏡下 未見(jiàn)明顯異常 右下肺灌洗和刷檢 未見(jiàn)惡性細(xì)胞 TB陰性 2010 10 12B院CT引導(dǎo)下經(jīng)皮肺穿刺 病理結(jié)果確診 肺隱球菌病上皮樣肉芽腫性病變 成堆隱球菌 幾點(diǎn)疑問(wèn) 真菌病一般都是免疫功能低下的患者隱球菌如何侵襲到肺的LA試驗(yàn)陰性肺隱球菌病CT表現(xiàn)和肺炎一樣 關(guān)于隱球菌 帶厚莢膜的酵母菌 乳膠凝集試驗(yàn) 腐生菌 土壤 鴿糞 霉?fàn)€蔬菜 水果等感染部位 中樞神經(jīng)系統(tǒng) 皮膚 肺感染途徑 吸入呼吸道經(jīng)血行播散到其它部位分型 17個(gè)種 18個(gè)變種 新生隱球菌及變種具有致病性 EpidemiologyI Amulticentreretrospectivestudyofpulmonarymycosisclinicallyprovenfrom1998to2007Totally474casesofpulmonarymycosisfrom16centersin10cities pulmonaryaspergillosis 180cases 37 9 pulmonarycandidiasis 162cases 34 2 pulmonarycryptococcosis 74cases 15 6 pneumocystiscafiniipneumonia 23cases 4 8 pulmonarymucormycosis 10cases 2 1 中華結(jié)核和呼吸雜志 2011 34 2 EpidemiologyII Meta AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69 7 patientshadnounderlyingdiseases Thecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome AIDS diabetesmalignanttumor中國(guó)臨床醫(yī)學(xué) 2013 20 3 351 354 EpidemiologyIII Retrospectiveinvestigationof151pulmonarycryptococcosisnon HIVcasesbetween1977and201244 4 patientshadnoUDs ThecommonUDswerediabetes 32 1 hematologicdisease 22 6 collagendisease 22 6 JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases JInfectChemother 2014Oct29 EpidemiologyIV 219patientswithprovencryptococcosisat20hospitalsinTaiwan 1997 2010210isolateswereC neoformans 95 9 9isolateswereC gattii 4 1 15 4 didnothaveanyunderlyingcondition HIVinfectionwasthemostcommonunderlyingcondition 54 219 24 6 AmongHIV negativepatients liverdiseases HBVcarrierorcirrhosis werecommon 30 2 TaiwanInfectiousDiseasesStudyNetworkforCryptococcosis PLoSOne 2013Apr17 8 4 e61921 EpidemiologyV Clinicalanalysisof76patientspathologicallydiagnosedwithpulmonarycryptococcosis Of76patients 54malesand22females 41 53 95 wereimmunocompetentand35outofthe41wereasymptomatic ShanghaiPulmonaryHospital EurRespirJ 2012Nov 40 5 1191 200 summary approximatelyhalfofpatientshadnounderlyingdiseasesasignificantnumberofpatientswereasymptomatic pathogenesis ThecapsuleisthemostimportantvirulencefactorofthefungalpathogenCryptococcusneoformans ThestructureProductionOfthecapsuleadhesionofCryptococcusneoformanstoepitheliallungcellsprotectiveimmuneresponsesagainstcryptococcosis Thestructureofcapsule Thisstructureconsistsofhighlyhydratedpolysaccharides includingglucuronoxylomannan GXM 葡萄糖醛酸木糖甘露聚糖galactoxylomannan GalXM 半乳糖木糖甘露聚糖mannoproteins MPs 甘露糖蛋白 lessthan1 ofthecapsularweight ProductionOfthecapsuleI CA CO2 sensingpathways 1Regulationofcapsulesynthesisbycarbondioxide JClinInvest 1985 76 2 508 516 2ComparativetranscriptomeanalysisoftheCO2sensingpathwayviadifferentialexpressionofcarbonicanhydraseinCryptococcusneoformans Genetics 2010Aug 185 4 1207 19 ProductionOfthecapsuleII cryptococcalpolysaccharidesynthesisisincreasedbylimitationofferricironavailabilitytothecellandbydissolvedCO2 andthetwoeffectsareadditive Regulationofcryptococcalcapsularpolysaccharidebyiron JInfectDis 1993Jan 167 1 186 90 ProductionOfthecapsuleIII capsuleenlargementinlivingC neoformanscellswasinfluencedbyCa 2 intheculturemedium EukaryotCell 2007Aug 6 8 1400 10 ProductionOfthecapsuleIV basedontheaxiallengtheningofPSmolecules CapsuleofCryptococcusneoformansgrowsbyenlargementofpolysaccharidemolecules ProcNatlAcadSciUSA 2009Jan27 106 4 1228 33 PS etccapsule alveolarmicroenvironment adhesiontoepitheliallungcells anadhesion likeinteractionbetweenMPonthefungalsurfaceandthecomplementaryreceptormoleculesontheepithelialcells FrontCellInfectMicrobiol 2014Aug19 4 106 Phagocytosisdefence SizeofCryptococcusneoformans DynamicchangesinthemorphologyofCryptococcusneoformansduringmurinepulmonaryinfection GXMagainstalveolarmacrophages AM Mechanismsofimmuneevasioninfungalpathogens 1Microbiology 2001Aug 147 Pt8 2355 65 2CurrOpinMicrobiol 2011Dec 14 6 668 75 immuneresponse SP DincreasessusceptibilitytoC neoformansinfectionbypromotingC neoformans drivenpulmonaryIL 5andeosinophilinfiltration Th1 Th2cytokineimbalance BcellsprovideafirstlineofdefenseduringpulmonaryC neoformansinfectioninmice1GenetMolRes 2013Nov18 12 4 5733 422InfectImmun 2014Feb 82 2 683 933JImmunol 2012Dec15 189 12 5820 30 Myopinioni ChangealveolarmicroenvironmentAbrogationofIL 4receptor dependentalternativelyactivatedmacrophagesissufficienttoconferresistanceagainstpulmonarycryptococcosisdespiteanongoingT h 2response IntImmunol 2013Aug 25 8 459 70 RadiologyI Peripherallydistributedpulmonarynodules massesweremostcommonlyseen JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases JInfectChemother 2014Oct29Radiological computedtomography findingsshowedpredominantlyperipheralfindings 85 53 includingnodularmasses 55 26 pneumonicinfiltrates 23 68 andmixedtype 21 05 ShanghaiPulmonaryHospital EurRespirJ 2012Nov 40 5 1191 200 71 8 patientswerecharacterizedbynodularlumpshadows 23 8 byflake likeinfiltratedshadows and7 4 haddiffusemixedlesions ZhongshanHospital ChineseJournalofClinicalMedicine 2013 RadiologyII CTscanfindingsof29immunocompetentand43immunocompromisedpatientsPulmonarynodules masses eithersolitaryormultiple werethemostcommonCTfinding presentin65 90 3 ofthe72patientsCavitationswithinnodules massesweremorecommonlyseeninimmunocompromisedpatients especiallyAIDSpatientsairbronchogramsweremorecommonlyseeninimmunocompetentpatientsPulmonarycryptococcosis comparisonofCTfindingsinimmunocompetentandimmunocompromisedpatients ActaRadiol 2014Apr22 Myopinionii Molecular functionalradiology currentsituationindiagnosis 43 42 33 76 wereinitiallymisdiagnosed oftenascancerbyfalse positive 18 FDG PETFailureofthecryptococcalser