肺隱球菌病 PC pulmonarycryptococcosis 從一個病例談起 復旦大學附屬華山醫院北院呼吸科張有志 病史介紹 患者 女性 47歲主述 因 反復咳嗽伴胸痛1月 入院 B院 現病史 患者于2010 9 5無明顯誘因出現咳嗽 少量白痰 伴右側胸痛 陣發性鈍痛 深吸氣時明顯 無放射痛 無發熱 無嘔吐 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 繼續口服莫西沙星6天 2010 9 27復查CT無吸收 于2010 10 12就診B院 既往 體健 否認性病冶游史 家中曾養寵物 鴿子 狗 查體 T 37 9 淺表淋巴結不大 右下肺可及濕啰音 輔助檢查 血常規 肝腎功能 D 二聚體正常 ESR 65mm h CRP 48mg L 血氣分析正常 HIV PPD試驗陰性 LA試驗 G試驗陰性 送至C院檢測 2010 9 6A院CT 2010 9 27A院CT 病史介紹 A院氣管鏡檢查 鏡下 未見明顯異常 右下肺灌洗和刷檢 未見惡性細胞 TB陰性 2010 10 12B院CT引導下經皮肺穿刺 病理結果確診 肺隱球菌病上皮樣肉芽腫性病變 成堆隱球菌 幾點疑問 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試驗陰性肺隱球菌病CT表現和肺炎一樣 關于隱球菌 帶厚莢膜的酵母菌 乳膠凝集試驗 腐生菌 土壤 鴿糞 霉爛蔬菜 水果等感染部位 中樞神經系統 皮膚 肺感染途徑 吸入呼吸道經血行播散到其它部位分型 17個種 18個變種 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 中華結核和呼吸雜志 2011 34 2 EpidemiologyII Meta AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69 7 patientshadnounderlyingdiseases Thecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome AIDS diabetesmalignanttumor中國臨床醫學 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