從心肌炎組織切片探討常見的致病DNA病毒

Identify the common DNA viral pathogens from formalin-fixed paraffin-embedded myocardium tissues of myocarditis

莊傑仰(Jie-Yang Jhuang)

指導教授 ： 孫家棟

國立臺灣大學/醫學院/法醫學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.10315

摘要

心肌炎（myocarditis）是一種心臟肌肉組織發炎的疾病，且伴隨著心臟功能缺損（cardiac dysfunction）。因為心肌炎有著多變的臨床表現，從一般無明顯徵候、似心肌梗塞的胸痛、心律不整、乃至於猝死都可能，病情迅速惡化常使醫師措手不及，是引起醫療糾紛的病症之一。法醫師常會參與此類死因鑑定，所以心肌炎是個重要的疾病，需要深入研究和了解。
目前在臨床上確定診斷心肌炎需要依靠經心導管心肌切片（endomyocardial biopsy, EMB）後，根據Dallas criteria來做病理診斷。心肌炎的病因很多種，光從型態學上的診斷，不免在先天上受制在致病源上的偵測。國外文獻認為大多數的病源是RNA病毒，我國亦研究RNA病毒為主，所以國內一直缺乏DNA病毒的流行病學資料，本研究想要了解心肌炎中DNA病毒感染的盛行率。於是收集2001年至2005年台大醫院因心肌炎入院病例中，心臟組織病理切片符合Dallas criteria的案例，利用巢式聚合酶連鎖反應加上毛細管電泳從舊組織切片（Archive tissue）中偵測ＤNA病毒基因，包括疱疹病毒第一型（HHV-1）、疱疹病毒第二型（HHV-2）、疱疹病毒第四型（HHV-4）和巨細胞病毒（HHV-5）。共有收集到二十四個檢體，年齡層分佈為六歲到四十八歲。十二個檢體為實驗組，病理診斷為心肌炎，有二個存在巨細胞病毒（human herpes virus 5，Cytomegalovirus），比率為16.7%（2/12）。另外十二個檢體來自法醫解剖的心臟檢體，死因為非心臟因素造成的死亡，病毒反應均呈現陰性。毛細管電泳結果得到的產物大小雖然和理論大小不符，但是實驗組檢體和病毒株檢體大小是相吻合的。除了RNA病毒，DNA病毒亦佔了心肌炎病因的一部份，建議以後臨床上心肌炎的案例都要考慮偵測病毒感染。本方法也可以應用在法醫解剖心肌炎的研究上，了解是何種病毒感染會致死及其流行病學資料，將有助於臨床診斷、判斷預後、或者有可能使用抗病毒藥物治療、以及達到公衛上預防死亡的發生和減少醫療糾紛的功能。

關鍵字

心肌炎 ； 疱疹病毒 ； 巨細胞病毒 ； 巢式聚合酶連鎖反應 ； 舊組織切片

並列摘要

Fatal acute myocarditis is a common cause of alleged medicolegal investigation. Forensic pathologists frequently encounter these death investigations, so it is an important disease we have to understand. The etiology of myocarditis is usually inferred from clinical information and preliminary laboratory studies. This study was undertaken to evaluate the molecular analysis of endomyocardial archive tissues in identifying the possibility of common DNA viral pathogens. We collected all available clinical record and endomyocardial archive tissues for patients who had myocarditis recorded as the clinical diagnosis at the National Taiwan University Hospital from 2001 to 2005. Findings for all available patients（6 men and 6 women；median age, 26 years）with myocarditis that fulfilled the Dallas criteria were included in this study. Twelve subjects who had died naturally except heart diseases served as control group from forensic autopsy. Nested polymerase chain reaction （PCR）was used for detection of DNA viral genomes （human herpes virus 1, human herpes virus 2, Epstein-Barr virus, and human herpes virus 5）from endomyocardial biopsied tissues. DNA viral nucleic acid were found in the hearts of 2 patients （16.7%）, including human herpes virus 5（2 patient）. In the control group, no viral genome was detected. In patients with unexplained myocarditis, viral infection really contributes to be an important etiology. We can’t realize which kinds of DNA viral infection based on only microscopic examination of endomyocardial biopsies. Serological tests can help these but it is time-consuming and not very specific. Nested polymerase chain reaction may be an sensitive and specific tool to identify viruses. Then, this may be given as a guide in treating patients in the future, such as viral vaccine prevention. It may be useful in forensic cases to identify the underlying virus infection.

並列關鍵字

Myocarditis ； Herpesviridae ； Human herpes virus 5 ； Nested polymerase chain reaction ； Archive tissue

參考文獻

1. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 1996;93(5):841-2.

2. Costantini M, Tritto C, Licci E, et al. Myocarditis with ST-Elevation Myocardial Infarction presentation in young man. A case series of 11 patients. Int J Cardiol 2005;101(1):157-8.

3. Angelini A, Calzolari V, Calabrese F, et al. Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy in the differential diagnosis. Heart 2000;84(3):245-50.

4. Kyto V, Saukko P, Lignitz E, et al. Diagnosis and presentation of fatal myocarditis. Hum Pathol 2005;36(9):1003-7.

5. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol 1987;18(6):619-24.