1、肺隐球菌病医学知识肺隐球菌病医学知识患者，女性，47岁主述：主述：因“反复咳嗽伴胸痛1月”入院（B院）现病史：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：既往：体健。否认性病冶游史。家中曾养宠物（鸽子、狗）。查体：查体：T：37.9，浅表淋巴结不大，右下肺可及湿啰音。辅助检查：辅助检查：血常规、肝肾功能、D-二聚体正常；ESR：65mm/h，
2、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）肺隐球菌病医学知识2肺隐球菌病医学知识3A院气管镜检查：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。肺隐球菌病医学知识4 病理结果确诊：肺隐球菌病上皮样肉芽肿性病变；成堆隐球菌肺隐球菌病医学知识5 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表现和肺炎一样肺隐球菌病医学知识6 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
3、：17个种、18个变种（新生隐球菌及变种具有致病性）肺隐球菌病医学知识7A multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007Totally 474 cases of pulmonary mycosis from 16 centers in10 cities.pulmonary aspergillosis(1 80 cases，379)pulmonary candidiasis(162 cases，342)pulmonary cryptococcosis(74 case
4、s，156)pneumocystis cafinii pneumonia(23 cases，4.8)pulmonary mucormycosis(10 cases，21)中华结核和呼吸杂志，2011,34(2)肺隐球菌病医学知识8 Meta-Analysis of Clinical Manifestations of Pulmonary Cryptococcosis in China Mainland 69.7%patients had no underlying diseases The common underlying diseases wereacquired immune defic
5、iency syndrome(AIDS)diabetesmalignant tumor 中国临床医学，2013,20（3）：351-354肺隐球菌病医学知识9 Retrospective investigation of 151 pulmonary cryptococcosis non-HIV cases between 1977 and 2012 44.4%patients had no UDs.The common UDs were diabetes(32.1%)hematologic disease(22.6%)collagen disease(22.6%)Japanese Societ
6、y of Chemotherapy and The Japanese Association for Infectious Diseases.J Infect Chemother.2014 Oct 29 肺隐球菌病医学知识10 219 patients with proven cryptococcosis at 20 hospitals in Taiwan,1997-2010 210 isolates were C.neoformans(95.9%);9 isolates were C.gattii(4.1%).15.4%did not have any underlying conditio
7、n.HIV infection was the most common underlying condition(54/219,24.6%).Among HIV-negative patients,liver diseases(HBV carrier or cirrhosis)were common(30.2%)Taiwan Infectious Diseases Study Network for Cryptococcosis.PLoS One.2013 Apr 17;8(4):e61921.肺隐球菌病医学知识11 Clinical analysis of 76 patients patho
8、logically diagnosed with pulmonary cryptococcosis.Of 76 patients(54 males and 22 females),41(53.95%)were immunocompetent and 35 out of the 41 were asymptomatic.Shanghai Pulmonary Hospital.Eur Respir J.2012 Nov;40(5):1191-200.肺隐球菌病医学知识12 approximately half of patients had no underlying diseases a sig
9、nificant number of patients were asymptomatic肺隐球菌病医学知识13 The capsule is the most important virulence factor of the fungal pathogen Cryptococcus neoformans.The structure Production Of the capsule adhesion of Cryptococcus neoformans to epithelial lung cells protective immune responses against cryptoco
10、ccosis 肺隐球菌病医学知识14 This structure consists of highly hydrated polysaccharides,including glucuronoxylomannan(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，less than 1%of the capsular weight肺隐球菌病医学知识15 CA/CO2-sensing pathways.1 Regulation of capsule synthesis by carbon d
11、ioxide J Clin Invest，1985，76(2):508-516 2 Comparative transcriptome analysis of the CO2 sensing pathway via differential expression of carbonic anhydrase in Cryptococcus neoformans.Genetics.2010 Aug;185(4):1207-19.肺隐球菌病医学知识16 capsule enlargement in living C.neoformans cells was influenced by Ca(2+)i
12、n the culture medium.Eukaryot Cell.2007 Aug;6(8):1400-10.肺隐球菌病医学知识18 based on the axial lengthening of PS molecules.Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules.Proc Natl Acad Sci U S A.2009 Jan 27;106(4):1228-33.PS，etc capsule?alveolar microenvironment 肺隐球菌病医学
13、知识19 an adhesion-like interaction between MP on the fungal surface and the complementary receptor molecules on the epithelial cells.Front Cell Infect Microbiol.2014 Aug 19;4:106.肺隐球菌病医学知识20 Size of Cryptococcus neoformans.Dynamic changes in the morphology of Cryptococcus neoformans during murine pul
14、monary infection.GXM against alveolar macrophages(AM).Mechanisms of immune evasion in fungal pathogens.1 Microbiology.2001 Aug;147(Pt 8):2355-65.2 Curr Opin Microbiol.2011 Dec;14(6):668-75.肺隐球菌病医学知识21 SP-D increases susceptibility to C.neoformans infection by promoting C.neoformans-driven pulmonary
15、IL-5 and eosinophil infiltration.Th1/Th2 cytokine imbalance.B cells provide a first line of defense during pulmonary C.neoformans infection in mice 1 Genet Mol Res.2013 Nov 18;12(4):5733-42 2 Infect Immun.2014 Feb;82(2):683-93 3 J Immunol.2012 Dec 15;189(12):5820-30 肺隐球菌病医学知识22 Change alveolar micro
16、environment Abrogation of IL-4 receptor-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response.Int Immunol.2013 Aug;25(8):459-70.肺隐球菌病医学知识23 Peripherally distributed pulmonary nodules/masses were most common
17、ly seen.Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.J Infect Chemother.2014 Oct 29 Radiological(computed tomography)findings showed predominantly peripheral findings(85.53%)including nodular masses(55.26%),pneumonic infiltrates(23.68%)and mixed type(21.05%).
18、Shanghai Pulmonary Hospital.Eur Respir J.2012 Nov;40(5):1191-200.71.8%patients were characterized by nodular lump shadows;23.8%by flake-like infiltrated shadows，and 7.4%had diffuse mixed lesions Zhongshan Hospital.Chinese Journal of Clinical Medicine，2013肺隐球菌病医学知识24 CT scan findings of 29 immunocomp
19、etent and 43 immunocompromised patients Pulmonary nodules/masses,either solitary or multiple,were the most common CT finding,present in 65(90.3%)of the 72 patients Cavitations within nodules/masses were more commonly seen in immunocompromised patients,especially AIDS patients air bronchograms were m
20、ore commonly seen in immunocompetent patients Pulmonary cryptococcosis:comparison of CT findings in immunocompetent and immunocompromised patients.Acta Radiol.2014 Apr 22.肺隐球菌病医学知识25 Molecular/functional radiology肺隐球菌病医学知识26 43.42%(33/76)were initially misdiagnosed,often as cancer by false-positive(
21、18)FDG-PET Failure of the cryptococcal serum antigen test to detect primary pulmonary cryptococcosis in patients infected with human immunodeficiency virus 26.2%（17/65）were confirmed by surgery 1 Shanghai Pulmonary Hospital.Eur Respir J.2012 Nov;40(5):1191-200.2 Clin Infect Dis.1994 Jan;18(1):119-20
22、.3 南京军区总医院.中华结核和呼吸杂志，2014,37（10）：764-768肺隐球菌病医学知识27 BALF-LAT Alveolar pucture fluid（CT guided transthoracic needle aspiration Biopsy）-LAT肺隐球菌病医学知识28 LAT EOS CT肺隐球菌病医学知识29 At present,there is not a suitable indicator for monitoring the disease肺隐球菌病医学知识30IDSA Clinical Infectious Disease，2010，50（3）：291-322ATS Am J Respir Cit CareMed，2011，183(1)：96-128隐球菌感染诊治专家共识 中国真菌学杂志 2010,5（2）：65-68肺真菌病诊断和治疗专家共识 中华结核和呼吸杂志 2007,30（11）：821-834肺隐球菌病医学知识31 Thanks肺隐球菌病医学知识32
