兒童特發性關節炎和腸病毒的風險分析：一個台灣健保資料庫病例對照研究

Risk Assessment of Juvenile Idiopathic Arthritis After Enterovirus Infection: A Case-Control Study From the National Health Insurance Research Database in Taiwan

謝宗學(Tsung-Hsueh Hsieh)

指導教授 ： 孫海倫

共同指導教授 ： 魏正宗(Cheng-Chung Wei)

中山醫學大學/醫學院/醫學研究所/碩士(2021年)

https://doi.org/10.6834/csmu202100243

摘要

研究目的：兒童特發性關節炎(Juvenile Idiopathic Arthritis，JIA)是兒童最常見的風濕病之一，成因至今仍然不清楚，一般認為遺傳基因和環境感染是可能的原因。腸病毒是台灣兒童常見的感染症疾病之一，藉由台灣健保資料庫大數據分析，試圖找出可能造成兒童特發性關節炎的風險因子，分析和兒童罹患腸病毒的關係，進一步釐清成因。

研究方法及資料：此研究是回溯性重疊病例對照研究，我們利用台灣2001 到 2013 年間的健保資料庫，根據國際疾病分類，使用第九版的臨床診斷代碼（The International Statistical Classification of Diseases and Related Health Problems 9th Revision, ICD-9），針對年齡小於16歲的病人，以至少兩次門診或至少一次住院的條件診斷兒童特發性關節炎，並依照年齡和性別以 1:8 的比例，將研究對象分成疾病組和對照組，最後疾病組的人數是495人，非疾病組的人數是3960人。再利用邏輯回歸統計分析，分析疾病組和對照組兩者和疾病診斷前5年感染腸病毒的勝算比，探討腸病毒對於兒童特發性關節炎的風險。

研究結果：本研究觀察到診斷前5年曾經感染腸病毒在罹患兒童特發性關節炎的疾病組裡的比例較對照組高(13.94%和11.24%)，但勝算比(crude odds ratio, cOR和adjusted odds ratio, aOR)並沒有發現統計學上的意義；若將感染腸病毒的時間縮短至診斷前2年，疾病組和對照組的勝算比cOR(95%信賴區間) 為1.51(1.04-2.19) 有統計學意義，但經過調整年齡、性別、城鄉、收入、和共病後的aOR達不到統計學意義。此外，分析診斷前5年內腸病毒就診次數，發現超過兩次以上(≥3次)腸病毒就診，疾病組和對照組的勝算比，不管是 cOR或 aOR皆達到統計學意義。

結論與建議：兒童曾經罹患腸病毒會增加兒童特發性關節炎的風險。因此，若兒童曾經感染腸病毒或多次因為腸病毒就診，需要同時注意兒童特發性關節炎的相關症狀。有效的腸病毒疫苗可能降低兒童特發性關節炎的發生率。

關鍵字

兒童特發性關節炎 ； 腸病毒 ； 健保資料庫 ； 重疊病例對照研究

並列摘要

Objective: Juvenile idiopathic arthritis (JIA) is one of the most common rheumatoid diseases in children. The cause of JIA is still not clear, but seems to be related to genetic factors and environmental infections. Enterovirus infection is one of the most common pediatric infectious diseases in Taiwan. We investigated the risk factors of JIA and analyzed the association of enterovirus infection and JIA by using the National Health Insurance Research Database (NHIRD) in Taiwan.

Methods and Materials: We conducted a retrospective nested case-control study, and the database was from NHIRD in Taiwan. According to the International Statistical Classification of Diseases and Related Health Problems 9th Revision (ICD-9), we enrolled the children aged less than 16 years who had been diagnosed as JIA and had at least outpatient clinics twice or admission once between 2001 to 2013. The control group and case group were 8:1 individual age and sex matched at the index date. Finally, 495 children were enrolled in case group, and 3960 were enrolled in control group. By using logistic regression model, we analyzed odds ratio between case group and control group related to the exposure of previous enterovirus infection among 5 years before the index date.

Results: We observed that the case group had higher incidence of enterovirus infection among 5 years before index date than the control group (13.94% versus 11.24%), but there was no statistical significance about crude odds ratio(cOR) or adjusted odds ratio(aOR). We focused on the exposure of enterovirus infection among 2 years before index date, and there was statistical significance about cOR. The case group had a 1.51-fold (95% CI, 1.04-2.19) increased JIA risk than control group. However, there was no statistical significance about aOR adjusted by age, sex, urbanization, low income, and co-morbidities. Furthermore, we observed that there was statistical significance about cOR and aOR between the case group and control group related to more than 2 medical visits for enterovirus infection among 5 years before index date.

Conclusion and Suggestion: Our study found that children with previous enterovirus infection had a increased risk of JIA. Therefore, pediatricians should pay attention to the symptoms about JIA if children ever have enterovirus infection or many medical visits for enterovirus infection. The effective enterovirus vaccine may decrease the incidence of JIA.

並列關鍵字

juvenile idiopathic arthritis (JIA) ； enterovirus ； national health insurance research database (NHIRD) ； nested case-control study

參考文獻

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