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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
dc.contributor.author | Chun-Jung Tsai | en |
dc.contributor.author | 蔡君蓉 | zh_TW |
dc.date.accessioned | 2021-06-16T05:09:21Z | - |
dc.date.available | 2014-10-15 | |
dc.date.copyright | 2014-10-15 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-19 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55842 | - |
dc.description.abstract | 背景:
Henoch-Schönlein purpura (HSP)又稱為過敏性紫斑症,是兒童最常見之全身性小血管炎,病因尚不明確,先前曾有論文發表因感染、藥物,以及注射疫苗而誘發HSP。HSP之發生有季節性,好發於秋冬與早春,暗示此病可能與某些感染或注射流感疫苗有關。Watanabe T.等人於2009年發表4位日本患者於接受H1N1新流感疫苗後發生HSP的案例報導。Weiss等於美國進行一回溯性研究,並於2010年發表結果於Journal of Rheumatology,研究顯示在某些月份因A型鏈球菌、金黃色葡萄球菌或副流感病毒感染的住院率與HSP住院率有顯著相關。台灣目前仍無探討感染症與HSP相關性之大型研究報告,因此我們擬利用全民健保資料庫,結合衛生福利部疾病管制署的傳染病統計資料,探討HSP與病原感染之相關性。 方法: 從1999年1月1日至2009年12月31日共11年間之健保資料庫中,依ICD-9-CM碼(287.0)搜尋經專科醫師診斷為HSP,且排除同時有其他風濕病診斷之門診及住院病患,並依美國風濕病學會(ACR)的HSP診斷標準,選擇小於20歲的患者,以SAS 9.1.3 for Windows分析患者之性別、發病年齡、住院期間與疾病預後等資料。台灣小於20歲人口的性別與年齡之流行病學分布,係來自於內政部戶政司的歷年全國人口統計資料。由於無法使用健保資料庫來分析國內某些特定病原感染的流行病學資料,故我們申請衛生福利部疾病管制署的傳染病監測統計資料,包括病毒性疾病檢測資料表與法定傳染病個案通報系統資料庫。實驗室監視通報系統自1999年3月開辦,係全國各級醫療院所檢送疑似病毒性疾病之檢體至該轄區合約實驗室的檢測結果,每筆資料皆包括性別、發病年齡、發病日期、臨床診斷、檢體來源、採檢日期與檢驗結果。法定傳染病則申請侵襲性b型嗜血桿菌感染症(自1999年開始)、腸病毒感染併發重症(自1999年開始)、流感併發重症(自2000年開始)與侵襲性肺炎鏈球菌感染症(自2007年10月開始),每筆資料皆包括性別、發病年齡、發病日期、通報疾病、確定病名、診斷日期、是否採檢及是否死亡。上述感染症皆僅分析小於20歲的確定病例。考量實驗室監視通報系統開辦初期資料尚不成熟,故病毒性疾病的分析期間選擇2001年1月至2009年12月,法定傳染病的分析期間則為該感染症開始列入法定傳染病起至2009年12月,採用卜瓦松自我迴歸傅立葉(PARF)模型,以月為單位進行時間序列分析(time-series analysis),檢定上述病原感染與HSP發病時間之相關性。 結果與討論: 在1999年至2009年間,有8271位患者在20歲前被診斷為HSP;其中,有4317位(52.2%)住院治療,年發生率為每100,000名小於二十歲的人口中有10.8-14.7例。門診患者中,男女比為1.01,最常發生於10月至隔年3月間,平均發病年齡為8.2歲。自2006年開始,住院率逐年降低。住院患者中,男女比為1.21。比較先前HSP的回溯性研究,本研究的特點為試驗期間長、所分析之患者年齡範圍乃依據ACR HSP診斷標準,設定為小於20歲、資料來源為我國健保資料庫,包括所有投保患者的門診及住院醫療申報紀錄,與衛生福利部疾病管制署的傳染病監測統計資料,係以全國人口為母群體。本研究中HSP患者的流行病學資料與先前楊醫師的研究相較,本研究的門診患者無明顯性別差異、平均發病年齡較高、住院率較高、平均住院天數較短;兩研究重複了1999至2002年的4年期間,當中差異除了反映台灣近10多年來HSP患者的流行病學變化外,亦可能是因全民健保的普及、收費可親、出生率逐年降低及對兒童健康照護的重視等因素,造成兒童住院率提高及/或住院的疾病嚴重度降低等現象。 自1999年3月開始,腺病毒、腸病毒、流感、副流感與呼吸道融合病毒的確定病例,皆為男性稍多(55%)。腺病毒、腸病毒、副流感與呼吸道融合病毒的患者年齡層較低,95%發生在10歲前,呼吸道融合病毒感染,更是超過九成都在5歲前發生;流感病毒感染在10歲前發生的約佔六成。自1999年3月開始,流感與副流感之病例數逐年上升,可能與我國防疫政策及國內臨床醫師對類流感症候群的警覺性提高有關。腸病毒於2001、2005及2008年有較大規模的流行,與我國腸病毒71型病毒株發生同一血清型內及不同血清型間的基因重組有關。 法定傳染病資料庫中,侵襲性b型嗜血桿菌與侵襲性肺炎鏈球菌感染症的確定病例,八成在5歲以下;腸病毒併發重症,92.9%發生於5歲前;流感併發重症之平均年齡較大,約六成在10歲前發生,而有16%發生在15-20歲。侵襲性b型嗜血桿菌感染症之確定病例數自1999年起逐年下降,可能與國內嬰幼兒b型嗜血桿菌疫苗的施打率提高有關。近年來國內嬰幼兒肺炎鏈球菌疫苗的施打率亦提高許多,但因侵襲性肺炎鏈球菌感染症自2007年10月才列入我國第四類法定傳染病,故統計至2009年底之確定案例數無明顯變化。流感併發重症在2009年夏秋有一特別高峰,係因2009年4月H1N1新型流感疫情爆發。 自2001年1月至2009年12月間,感染腺病毒及副流感病毒與HSP的發病時間呈正相關,達統計顯著 (p值分別為0.0205及0.0446);而法定傳染病個案通報系統資料庫中,自各感染症開始監測起至2009年12月間,腸病毒併發重症及流感併發重症與HSP的發病時間呈顯著正相關,p值分別為0.0001及0.0067。據我們所知,目前僅有一例由Meadow等發表的腺病毒感染引發過敏性紫斑症腎炎的個案報告;一例由Lee等發表感染A型流感病毒後出現全身性小血管炎且經皮膚切片確定為白血球破碎性血管炎的個案報告;Costa等報告一案例為克沙奇病毒B1後出現白血球破碎性血管炎;Chia等發表一篇感染伊科病毒第七型後發生白血球破碎性血管炎的個案報告。已知H1N1新型流感的嚴重個案,其早期的免疫反應為活化Th1及Th17產生細胞激素,這些細胞激素會參與發炎與自體免疫反應而可能會誘發血管炎。另,推測在腸病毒血症時,病毒或病毒-抗體複合物會與血管內皮細胞上的CD55結合,使CD55減少,故抗腸病毒抗體與血管內皮細胞結合所誘發的補體系統會過度活化,因而產生白血球破碎性血管炎的臨床表徵。 結論: 我們的研究為第一篇探討特定病原感染與HSP發病時間相關性的大型臨床研究,顯示感染腺病毒、副流感病毒、腸病毒感染併發重症及流感併發重症與HSP的發病時間呈顯著正相關。雖然非前瞻性試驗,無法證實其直接相關性,但我們的試驗期間長、分析患者多,故研究結果可提供未來擬探討過敏性紫斑症病因之臨床試驗作為參考。 | zh_TW |
dc.description.abstract | Background and objective:
Henoch-Schönlein purpura (HSP) is the most common systemic small vessel vasculitis of children. HSP is characterized by seasonal variation, with most cases occurring in the winter or spring. Although the etiology of HSP remains unclear, the seasonal nature suggests that antecedent infections at least partially contribute to disease pathogenesis. We choose an indirect method to evaluate at a national population level whether the outbreaks of certain pathogens are significantly correlated with the onset of HSP. Methods: We conduct a retrospective cohort study using the administrative database of Bureau of the NHI (BNHI), from 1 January 1999 to 31 December 2009, which contains comprehensive inpatient and outpatient data from all ranks of medical institutions in Taiwan. All patients below the age of 20 years (according to the ACR criteria) with the diagnosis of HSP and without other rheumatoid diseases were included into this study. Data for each patient including sex, age, date of onset, length of hospitalization, systemic organ involvement and discharge outcome were analyzed. The statistical analyses were conducted using SAS 9.1.3 for Windows. We also utilized the data of Notifiable Infectious Diseases Statistics System (NIDSS) from the Center for Disease Control (CDC) and used Poisson-autoregressive-Fourier (PARF) modeling with identity link on the time series data to study the association between the onset of HSP and certain pathogen infections, including influenza/parainfluenza viruses, enteroviruses, respiratory syncytial virus (RSV), adenovirus, invasive pneumococcal diseases, invasive Haemophilus influenzae type B (Hib) diseases, enterovirus infection with severe complications and severe complicated influenza on a monthly basis. Results and Discussion: During the 11-year study period, a total of 8271 patients below the age of 20 year had ever visited outpatient department (OPD) for HSP, and a total of 4317 HSP patients had ever hospitalized. The mean age at onset is 8.2 years. Among the overall population below the age of 20 year in Taiwan, the annual incidence was 10.8 to 14.7 cases per 100,000 people. Among the OPD cases, a male to female ratio is 1.01. OPD visits were most frequent in October through March. Among the hospitalized cases, a male to female ratio is 1.21. The hospitalization rate is decreasing since 2006. Compare to previous retrospective studies of HSP, our study duration is the longest, the age selection of HSP patients is according to the ACR criteria, the data source is NHI database and NIDSS from CDC, and the population of our study is national population. The comparison of this study and the previous HSP study using NHI database in Taiwan from 1999 to 2002 by Yang et al. shows our OPD patients are of no gender difference, the mean age at onset and the hospitalization rates are higher, and the mean duration of hospitalization is shorter. These differences may be due to the change of demographics of HSP patients in recent 10 years in Taiwan. In addition, the universal and quality healthcare provided by the NHI system to the people of Taiwan at affordable cost, the decreasing birth rates and our attention to child care may result in the increasing children hospitalization rates and the decreasing severity of hospitalized children. The confirmed cases of adenovirus, enteroviruses, influenza, parainfluenza and RSV infections, as well as invasive Hib diseases, invasive pneumococcal diseases, enterovirus infection with severe complications and severe complicated influenza are more males (55%). Ninety-five percent of the cases of adenovirus, enteroviruses, parainfluenza and RSV infections occurred before 10 years of age; more than 90% of cases of RSV infections are before the age of 5; about 80% of cases of invasive Hib and pneumococcal diseases are before the age of 5; about 60% cases of influenza virus infections are before 10 years of age. The increasing rates of influenza and parainfluenza infections since March 1993 are probably due to our national epidemic prevention policy and the alertness of clinical physicians to influenza syndrome. The reason for the decreasing of confirmed case numbers of invasive Hib diseases since 1999 may be due to the increasing vaccination rates of Hib vaccine. The pneumococcal vaccination rates were also increasing in recent years in Taiwan, but there is no obvious change of case numbers of invasive pneumococcal diseases because the time of invasive pneumococcal diseases being listed in the notifiable infectious diseases began in October 2007, and the duration between October 2007 and December 2009 is short. From January 2001 to December 2009, the onset of HSP was significantly related to the infectious of adenovirus and parainfluenza viruses (p = 0.0205 and p=0.0446, respectively). Form each infectious disease being listed in the notifiable infectious diseases in Taiwan to December 2009, the onset of HSP was significantly correlated with the occurrence of enterovirus infection with severe complications and severe complicated influenza (p = 0.0001 and p = 0.0067, respectively). To our knowledge, there is only one case report of Henoch-Schönlein nephritis after adenovirus infection by Meadow et al. Lee et al. reported a case of systemic small vessel vasculitis after influenza A and the histopathology of skin biopsy showing leukocytoclastic vasculitis. Costa et al reported one case of leukocytoclastic vasculitis occurred after coxsackievirus B1 infection, and Chia et al reported a case of leukocytoclastic vasculitis occurred after echovirus 7 infection. We already know that the early phase of immune responses in severe H1N1 influenza cases is to activate Th1 and Th17 cells to produce pro-inflammatory cytokines, which may induce vasculitis. Besides, it is supposed that the virus or virus-antibody complex can bind to the CD55 on vascular endothelial cells during the enteroviruses viremia and lead to CD55 decreasing, which in turn over-activates the induced complement system and produces the clinical manifestation of leukocytoclastic vasculitis. Conclusions: Our study is the first large clinical trial to evaluate the association between certain pathogen infections and the onset of HSP. The study results reveal that the onset of HSP was significantly correlated with the infectious of adenovirus and parainfluenza viruses as well as the occurrence of enterovirus infection with severe complications and severe complicated influenza. Although our study is not prospective and cannot demonstrate the direct association between the onset of HSP and these infectious diseases, the study duration is currently the longest and the population size is large. Therefore, our study results could provide some reference for future clinical studies designed to assess the etiology of HSP. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:09:21Z (GMT). No. of bitstreams: 1 ntu-103-P00421003-1.pdf: 1438667 bytes, checksum: 29d6065153f7a578d70e326acdf3876c (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 目 錄
口試委員會審定書………………………………………………………………… i 誌謝……………………………………………………………………………….… ii 中文摘要……………………………………………………………………………… v 英文摘要………………………………………………………………………….… viii 碩士論文內容 第一章 緒論………………………………………………………………….. 1 第二章 研究方法………………………………………………………………….. 7 2.1資料來源…………………………………………………………………… 7 2.2研究分析對象的選擇…………………………………………………… 10 2.3統計分析………………………………………………………………… 13 第三章 結果………………………………………………………………….. 14 3.1過敏性紫斑症的流行病學資料………………………………………… 14 3.2衛生福利部疾病管制署的傳染病監測統計資料的流行病學分析…… 16 3.3過敏性紫斑症的發生率與衛生福利部疾病管制署的傳染病監測統計資料中各感染症確定案例數之相關性…………………………………………… 19 第四章 討論………………………………………………………………….. 21 第五章 展望………………………………………………………………….. 27 第六章 參考文獻……………………………………………………………….. 28 第七章 圖表………………………………………………………………….. 35 表一…………………………………………………………………… 36 表二…………………………………………………………………… 37 表三…………………………………………………………………… 38 表四…………………………………………………………………… 39 表五…………………………………………………………………… 40 表六…………………………………………………………………… 41 表七…………………………………………………………………… 42圖一…………………………………………………………………… 43 圖二…………………………………………………………………… 44 圖三…………………………………………………………………… 45 圖四…………………………………………………………………… 46 圖五…………………………………………………………………… 47 圖六…………………………………………………………………… 48 圖七…………………………………………………………………… 49 圖八…………………………………………………………………… 50 圖九…………………………………………………………………… 51 圖十…………………………………………………………………… 52 圖十一…………………………………………………………………… 53 圖十二…………………………………………………………………… 54 圖十三…………………………………………………………………… 55 圖十四…………………………………………………………………… 56 圖十五…………………………………………………………………… 57 圖十六…………………………………………………………………… 58 圖十七…………………………………………………………………… 59 | |
dc.language.iso | zh-TW | |
dc.title | Henoch-Schönlein紫斑症與感染病原體之相關性 | zh_TW |
dc.title | The association between pathogen infections and the onset of Henoch-Schönlein purpura | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張鑾英(Luan-Yin Chang),楊曜旭(Yao-Hsu Yang) | |
dc.subject.keyword | 紫斑,感染症,流行病學,病毒感染,腸病毒,流感, | zh_TW |
dc.subject.keyword | purpura,epidemiology,infectious diseases,virus infection,enteroviruses,influenza, | en |
dc.relation.page | 59 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
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