藥物使用及共病情形對類天皰瘡發生率影響之探討：巢氏病例對照研究

The incidence of bullous pemphigoid and related clinical factors of medication and comorbidity in Taiwan: a nested case-control study

謝奇叡(Chi-Jui Hsieh)

指導教授 ： 葉志嶸

中山醫學大學/健康管理學院/公共衛生學系碩士班/碩士(2017年)

摘要

目的：大皰型類天皰瘡(BP)是一種罕見的自體免疫反應水皰病，擁有較高比例的共病症及致命性，但流行病學及臨床特徵尚不清楚。因此本研究進行巢氏病例研究，以顯示類天皰瘡的發病趨勢、用藥情形和共病症。
材料與方法：本研究為巢氏病例研究，資料來源為全民健保資料庫(LHID2000)，並依據ICD-9診斷標準定義出1998-2011年間罹患類天皰瘡的人數、用藥及共病症。罹患類天皰瘡的人數為528人，進行1比4配對得到2112名相同性別、年齡(±1歲)的對照樣本。本研究以SAS 9.4版統計軟體進行雙變項分析、多變項分析、分層分析及條件式羅吉斯迴歸。
研究結果：標準化類天皰瘡發病率範圍為1.28-3.04/100,000，年齡>70歲組的類天皰瘡發生率比年齡<50歲組高50-60倍。Loop(adjusted OR=1.93[1.45-2.58])、Calcium channelblockers(adjusted OR=1.50[1.17-1.91])、Antihypertensives, α-blockers(adjusted OR=1.51[1.05-2.17])、ARB(adjusted OR=1.61[1.18-2.19])、Aspirin(adjusted OR=1.46[1.13-1.89])、Clopidogrel(adjusted OR=2.72[1.54-4.81])、Hypotension & shock(adjusted OR=4.11[2.40-7.06])、Antianginal drugs-coronary vasodilators(adjusted OR=1.39[1.05-1.83])、Antiarrhythmics(adjusted OR=1.50[1.07-2.10])、Insulin(adjusted OR=3.70[2.31-5.93])、Iodide(adjusted OR=3.13[1.82-5.38])、Prednisolone(adjusted OR=3.17[2.50-4.00])、Immunosuppressive agents(adjusted OR=8.29[1.60-42.8])、Antibiotics(adjusted OR=2.75[2.14-3.52])、Gaviscon(adjusted OR=2.85[1.53-5.29])、Proton pump inhibitors(adjusted OR=3.22[2.17-4.79])、H2 antagonists(adjusted OR=1.36[1.05-1.76])、Laxatives(adjusted OR=3.23[2.48-4.19])、Urinary/prostatic medication, alpha blocker(adjusted OR=1.54[1.11-2.15])、Nasal decongestants(adjusted OR=5.13[1.65-16.02])、H1 Antihistamines(adjusted OR=1.94[1.55-2.42])和Vitamine(adjusted OR=1.73[1.36-2.21])與類天皰瘡的發生呈現顯著相關。中風(adjusted OR=2.79[2.02-3.85])、癡呆(adjusted OR=7.02[4.70-10.47])、帕金森氏症(adjusted OR=2.56[1.52-4.3])、癲癇(adjusted OR=5.03[2.49-10.15])和乾癬(adjusted OR=7.84[3.03-20.27])與類天皰瘡的發生呈現顯著相關。
結論及建議：台灣地區年齡大於70歲的老年人，類天皰瘡發病率比歐洲發達國家高5-30倍。Diuretics、Antihypertensives、Cardiovascular drugs、Antibiotics、Immunosuppressants、Gastrointestinal tract medications、Nasal medication、Endocrine/rheumatological medication、Vitamins的使用與類天皰瘡的發生呈現顯著相關。在台灣中風、癡呆、帕金森氏症、癲癇和乾癬的患者，有較高的機率罹患類天皰瘡。此研究結果顯示類天皰瘡與多種藥物和共病症之間的關係，揭示了未來類天皰瘡的研究和臨床實踐的方向，未來在使用與類天皰瘡有關之藥物以及共病時，須特別留意。

關鍵字

類天皰瘡 ； 發生率 ； 藥物使用 ； 共病症 ； 巢氏病例研究

並列摘要

Objectives:
The autoimmune skin disorder, bullous pemphigoid(BP), is associated with considerable morbidity and mortality, but the epidemiological and clinical characteristics are few in literatures. We carried out this nested case–control study to show the incidence trend, medication and neurological comorbidities of BP.
Methods:
The National Health Insurance dataset (LHID2000) was used for this study. BP and neurological disorders were defined according to the ICD-9 diagnostic codes. Each case was age-(±1 year) and sex-matched to four healthy controls. This study use SAS 9.4 for bivariate analysis, multivariate analysis, and conditional logistic regression.
Results:
The standardized BP incidence range is 1.28-3.04 per 100,000 and BP incidences in age≧70 group are 50-60 folds higher than in age<=50 group. Loop(adjusted OR=1.93[1.45-2.58])、Calcium channelblockers(adjusted OR=1.50[1.17-1.91])、Antihypertensives, α-blockers(adjusted OR=1.51[1.05-2.17])、ARB(adjusted OR=1.61[1.18-2.19])、Aspirin(adjusted OR=1.46[1.13-1.89])、Clopidogrel(adjusted OR=2.72[1.54-4.81])、Hypotension & shock(adjusted OR=4.11[2.40-7.06])、Antianginal drugs-coronary vasodilators(adjusted OR=1.39[1.05-1.83])、Antiarrhythmics(adjusted OR=1.50[1.07-2.10])、Insulin(adjusted OR=3.70[2.31-5.93])、Iodide(adjusted OR=3.13[1.82-5.38])、Prednisolone(adjusted OR=3.17[2.50-4.00])、Immunosuppressive agents(adjusted OR=8.29[1.60-42.8])、Antibiotics(adjusted OR=2.75[2.14-3.52])、Gaviscon(adjusted OR=2.85[1.53-5.29])、Proton pump inhibitors(adjusted OR=3.22[2.17-4.79])、H2 antagonists(adjusted OR=1.36[1.05-1.76])、Laxatives(adjusted OR=3.23[2.48-4.19])、Urinary/prostatic medication, alpha blocker(adjusted OR=1.54[1.11-2.15])、Nasal decongestants(adjusted OR=5.13[1.65-16.02])、H1 Antihistamines(adjusted OR=1.94[1.55-2.42])and Vitamine(adjusted OR=1.73[1.36-2.21]) are associated with incident BP. Stroke(adjusted OR=2.79[2.02-3.85])、Dementia(adjusted OR=7.02[4.70-10.47])、Parkinson(adjusted OR=2.56[1.52-4.3])、Epilepsy(adjusted OR=5.03[2.49-10.15])and Psoriasis(adjusted OR=7.84[3.03-20.27]) are highly associated with BP.
Conclusion:
BP incidences in Taiwan(age＞70) are 5-30 folds higher than in the developed European countries. Diuretics, Antihypertensives, Cardiovascular drugs, Antibiotics, Immunosuppressants, Gastrointestinal tract medications, Nasal medication, Endocrine/rheumatological medication and Vitaminsare associated with BP. Stroke、Dementia、Parkinson、Epilepsy and Psoriasis are highly associated with BP. The associations between BP and the use of multiple drugs and comorbidities shed light on future research and clinical practice of BP.

並列關鍵字

Bullous Pemphigoid ； incidence ； drug use ； comorbidity ； nested case–control

參考文獻

12. 呂耀卿, 類天疱瘡.當代醫學, 1985(138): p. 296-299.

13. 黃雅玲, 黃瓊瑰, and 曹國倩, 病毒感染的實驗室診斷.感染控制雜誌, 2006. 16(2): p. 109-116.

1. Lever, W.F., Pemphigus. Medicine, 1953. 32(1): p. 1-123.

2. Jordon, R.E., et al., Basement zone antibodies in bullous pemphigoid. Jama, 1967. 200(9): p. 751-756.

3. García‐Doval, I., et al., Bullous pemphigoid triggered by influenza vaccination? Ecological study in Galicia, Spain. British Journal of Dermatology, 2006. 155(4): p. 820-823.