肺隐球菌病

肺隐球菌病 PC pulmonarycryptococcosis 从一个病例谈起 复旦大学附属华山医院北院呼吸科张有志 病史介绍 患者 女性 47岁主述 因 反复咳嗽伴胸痛1月 入院 B院 现病史 患者于2010 9 5无明显诱因出现咳嗽 少量白痰 伴右侧胸痛 阵发性钝痛 深吸气时明显 无放射痛 无发热 无呕吐 头痛 某A院行胸部CT示 右下肺炎 予以莫西沙星静滴8天患者咳嗽 胸痛有所缓解 继续口服莫西沙星6天 2010 9 27复查CT无吸收 于2010 10 12就诊B院 既往 体健 否认性病冶游史 家中曾养宠物 鸽子 狗 查体 T 37 9 浅表淋巴结不大 右下肺可及湿啰音 辅助检查 血常规 肝肾功能 D 二聚体正常 ESR 65mm h CRP 48mg L 血气分析正常 HIV PPD试验阴性 LA试验 G试验阴性 送至C院检测 2010 9 6A院CT 2010 9 27A院CT 病史介绍 A院气管镜检查 镜下 未见明显异常 右下肺灌洗和刷检 未见恶性细胞 TB阴性 2010 10 12B院CT引导下经皮肺穿刺 病理结果确诊 肺隐球菌病上皮样肉芽肿性病变 成堆隐球菌 几点疑问 真菌病一般都是免疫功能低下的患者隐球菌如何侵袭到肺的LA试验阴性肺隐球菌病CT表现和肺炎一样 关于隐球菌 带厚荚膜的酵母菌 乳胶凝集试验 腐生菌 土壤 鸽粪 霉烂蔬菜 水果等感染部位 中枢神经系统 皮肤 肺感染途径 吸入呼吸道经血行播散到其它部位分型 17个种 18个变种 新生隐球菌及变种具有致病性 EpidemiologyI Amulticentreretrospectivestudyofpulmonarymycosisclinicallyprovenfrom1998to2007Totally474casesofpulmonarymycosisfrom16centersin10cities pulmonaryaspergillosis 180cases 37 9 pulmonarycandidiasis 162cases 34 2 pulmonarycryptococcosis 74cases 15 6 pneumocystiscafiniipneumonia 23cases 4 8 pulmonarymucormycosis 10cases 2 1 中华结核和呼吸杂志 2011 34 2 EpidemiologyII Meta AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69 7 patientshadnounderlyingdiseases Thecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome AIDS diabetesmalignanttumor中国临床医学 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