今日の臨床サポート

心筋炎(小児科)

著者: 香取竜生 公立昭和病院 小児科

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2019/10/30
参考ガイドライン:
日本小児循環器学会学術委員会:小児期急性・劇症心筋炎の診断と治療の指針. 日本小児循環器学会雑誌 2006;.22 (4):514-524.
日本循環器学会編:急性および慢性心筋炎の診断・治療に関するガイドライン. Circ J 2004; 68( Suppl. Ⅳ): 1231-1263.
患者向け説明資料

概要・推奨   

  1.  心筋炎は心筋の炎症性疾患であり、原因の多くはウイルス感染による。
  1.  小児の致死性心筋炎の頻度は10万人中0.5人との報告がある。死亡率は20%とされるが、生存例の2/3は後遺症なく回復する。
  1.  発熱、嘔吐・下痢、食欲不振等の非特異的な感冒症状、消化器症状から発症する。「ただの感冒にしては」とまず疑うことが重要である。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が 必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
香取竜生 : 特に申告事項無し[2021年]
監修:五十嵐隆 : 特に申告事項無し[2021年]

改訂のポイント:
  1.  定期レビューを行い、鑑別のポイントと用語の追加を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 心筋炎は心筋の炎症性疾患であり、原因の多くはウイルス感染による。(表<図表>
  1. 心筋壊死とともに炎症性物質による心筋細胞機能障害が起こり、心ポンプ失調、不整脈を来す。
  1. 小児期の心筋炎の40%は劇症型、50%が急性である。小児例全体の生存例は75%とされる、60%は後遺症なく退院する。小児心筋炎は小児剖検例の18%にあたり、うち57%は突然死である。小児の致死性心筋炎の頻度は10万人中0.5人との報告がある[1][2][3]
  1. 風邪症状や消化器症状などに続いて、数日から数時間で心不全症状、胸痛、不整脈が出現する。劇症型では、急速に心原性ショックや重症不整脈を呈する。
  1. 前駆症状として、発熱55%、嘔吐45%、胸痛27%が多くみられる。
  1. 不安感、顔面蒼白、低血圧、頻脈、奔馬調律(ギャロップ)、不整脈、胸痛、腹痛、頚静脈怒張、呼吸不全などがみられたときは心筋炎を疑う必要がある。(表<図表>
  1. 血液検査(心筋逸脱酵素、心筋トロポニン等)、心電図(ST-T異常、不整脈等)、胸部X線所見(心拡大、肺うっ血)、心エコー検査を行う。心エコーは特に有用である。
  1. 1~2週の炎症期ののち回復期に入る。急性期の治療としては回復期までの血行動態の維持(薬物療法、補助循環)が基本となる。特異的療法として、抗ウイルス薬、免疫抑制薬、大量免疫グロブリン療法がある。
  1. 回復期までの心不全管理が予後を左右する。心不全症状のみられる場合、できるだけ早期に、心筋生検を含む心臓カテーテル検査、大動脈内バルーンパンピング(IABP)や心肺補助循環など集中治療の可能な施設に搬送する。
 
  1. 小児期・新生児期の急性心筋炎の全国調査結果より劇症型心筋炎の特徴のまとめ(推奨度2)
  1. 対象:1984~93年に剖検で死因が確定した20歳未満の劇症型心筋炎患者11例[3]
  1. 年齢:平均11.5±5.5歳 10例が6歳以上。
  1. 前駆症状:発熱6例、嘔吐5例、胸痛3例、咳漱、不整脈各1例。
  1. 医療機関受診状況と死亡病日:4例は受診なく、うち2例は突然死。受診していた7例はいずれも前駆症状発症後3~4病日に死亡。
  1. 追記:非特異的な前駆症状と急速な経過に注意
 
  1. 日本における多施設でのアンケート調査のまとめ(推奨度2)
  1. 小児科学会認定施設627病院に対して、1997年1月~2002年12月までの5年間の小児期心筋炎経験例をアンケート調査した[4]。111施設から261症例の報告があり、そのうち161例について二次回答が得られた。劇症型が全体の約40%と多く、急性型と合わせた死亡率は約20%であった。生存例の約2/3は後遺症なく回復した。また、長期観察記での不整脈や心機能低下の遺残は比較的少なかった。治療として、ステロイドが26 %、免疫グロブリン大量療法が46 %、補助循環が約半数で有効と判断された。
  1. 病型:劇症型62 例(38.5 %)、急性85 例(52.8 %)、慢性7 例、不明7 例。
  1. 原因ウイルス:37 例(23.0 %)で判明。インフルエンザ 13例、コクサッキーウイルス A群6 例/B群9例、エコーウイルス 2例、エンテロウイルス属 2例、パルボウイルス 2例、サイトメガロウイルス 1例、麻疹 1例、ムンプス 1例。
  1. 初発症状:発熱86 例、悪心・嘔吐52 例、腹痛24 例。
  1. 心症状:心不全70 例、不整脈37 例、アダムス・ストークス発作/失神17 例、徐脈16 例。
  1. 入院時血液生化学検査:CK 5~38,100(CK-MB 1~1,525)IU/l、心筋トロポニンT<0.01~35.8 ng/ml、ミオシン軽鎖<0.1~120 ng/ml。
  1. 心エコー図(n=143):心収縮能低下117 例、心膜液貯留31 例、心筋肥厚15 例
  1. 心臓核医学:201Tl 集積:異常26、正常16。67Ga 集積:異常1、正常9。99mTc-ピロリン酸
  1. 集積:異常4、正常1。123I-MIBG 集積:異常19、正常4。
  1. 治療:大量免疫グロブリン療法:有効29(46 %)、無効16、不明28。ステロイド:有効11(26 %)、無効16、不明21。補助循環(IABP 4 例、PCPS 10 例、LVAS 0 例、ECMO 4 例):有効12、無効8、不明1。
  1. 転帰:生存120 例(74.5 %):後遺症なし 71 例、後遺症あり 49 例(心不全7、心機能低下29、不整脈10、弁膜症4、その他4)、再発/再燃なし77 例、死亡 39 例(18.6 %)。
  1. 長期観察期:正常 87 例(83 %)、異常 9 例、不変9 例、増悪 0 例。
  1. 不整脈:あり9 例(10 %)、なし28 例。
  1. 心機能低下:あり13 例(14.2 %)、なし78 例。
  1. 追記:国内における多施設へのアンケート調査のまとめである。確立したエビデンスのない現在、参考にすべきであろう。相当数の施設で免疫抑制療法、免疫グロブリン大量療法、補助循環が有用であると考えられている。
問診・診察のポイント  
  1. 発熱、嘔吐・下痢、食欲不振等の非特異的な感冒症状、消化器症状から発症する。鑑別疾患としての心筋炎が念頭にないと早期診断は困難である。

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文献 

著者: Ville Kytö, Antti Saraste, Liisa-Maria Voipio-Pulkki, Pekka Saukko
雑誌名: Am J Epidemiol. 2007 Mar 1;165(5):570-4. doi: 10.1093/aje/kwk076. Epub 2007 Jan 19.
Abstract/Text To study the incidence of fatal myocarditis in the general population, the authors retrospectively collected all death certificates recording myocarditis as the underlying cause of death in Finland in 1970-1998. The incidence of myocarditis and its proportion of all deaths were calculated from 141.4 million person-years and 1.35 million deaths. Myocarditis was recorded as the underlying cause of death in 639 cases. Thus, its death certificate-based incidence was 0.46 (95% confidence interval (CI): 0.43, 0.49) per 100,000 person-years, and it caused 0.47 (95% CI: 0.44, 0.51) of 1,000 deaths. The incidence of 0.51 (95% CI: 0.46, 0.56) in males was higher than the incidence of 0.42 (95% CI: 0.37, 0.47) in females, the odds ratio being 1.34 (95% CI: 1.15, 1.58) (p < 0.001). The proportion of deaths caused by myocarditis was highest (up to six of 1,000 deaths) in children and adults aged less than 45 years. Because previous histopathologic reanalysis showed that only 32% of cases fulfilled the Dallas criteria, the authors estimated the incidence of histopathologically certain fatal myocarditis to be 0.15 (95% CI: 0.13, 0.17) per 100,000. The death certificate-based incidence of fatal myocarditis was found to be 0.46 per 100,000, and the histopathologically corrected incidence was 0.15 per 100,000.

PMID 17237135  Am J Epidemiol. 2007 Mar 1;165(5):570-4. doi: 10.1093/a・・・
著者: Neil E Bowles, Jiyuan Ni, Debra L Kearney, Matthias Pauschinger, Heinz-Peter Schultheiss, Robert McCarthy, Joshua Hare, J Timothy Bricker, Karla R Bowles, Jeffrey A Towbin
雑誌名: J Am Coll Cardiol. 2003 Aug 6;42(3):466-72.
Abstract/Text OBJECTIVES: The purpose of this study was to analyze cardiac tissue and blood for viral genomes using polymerase chain reaction (PCR) to define the common viral etiologies of myocarditis by age group.
BACKGROUND: Enteroviruses are considered the most common cause of myocarditis at all ages. Diagnosis relies on viral cultures, serology, and cardiac histology, which lack sensitivity, as well as PCR. However, in many cases enteroviruses are not detected.
METHODS: Cardiac samples were obtained for PCR analysis from patients with myocarditis (n = 624) and dilated cardiomyopathy (DCM) (n = 149). Patients were analyzed by age group, including neonates (n = 116), infants (n = 191), toddlers (n = 87), children (n = 110), adolescents (n = 92), and adults (n = 177). After nucleic acids had been extracted from an endomyocardial biopsy, an explant, or autopsy samples, PCR and reverse transcription PCR were performed to detect the genomic sequences of enterovirus, adenovirus, cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), parvovirus, respiratory syncytial virus (RSV), and influenza A virus.
RESULTS: Viral genome was amplified (adenovirus = 142, enterovirus = 85, CMV = 18, parvovirus = 6, influenza A = 5, HSV = 5, EBV = 3, RSV = 1) from 239 (38%) of the 624 samples from myocarditis patients, including 26 patient samples in which dual infection was found. Virus was detected in 30 (20%) of 149 DCM patient samples; only adenovirus (n = 18) and enterovirus (n = 12) were detected.
CONCLUSIONS: Polymerase chain reaction identified adenovirus as the most common virus in the myocardium of children and adults with myocarditis and DCM. Although enteroviruses are also found in these patients, they appear to be a less common cause of myocarditis than adenovirus.

PMID 12906974  J Am Coll Cardiol. 2003 Aug 6;42(3):466-72.
著者: Naoyoshi Aoyama, Tohru Izumi, Katsuhiko Hiramori, Mitsuaki Isobe, Masatoshi Kawana, Michiaki Hiroe, Hitoshi Hishida, Yasushi Kitaura, Tsutomu Imaizumi, Japanese Investigators of Fulminant Myocarditis
雑誌名: Circ J. 2002 Feb;66(2):133-44.
Abstract/Text Although fulminant myocarditis is known as a fatal disease, patients have been able to recover and return to normal life with the help of mechanical cardiopulmonary support. However, therapeutic guidelines for using percutaneous cardiopulmonary support (PCPS) for fulminant myocarditis have not been established, and the clinical course and long-term prognosis of such patients are still controversial issues. The present national survey considered the current situation of patients as the basis for proposing therapeutic guidelines. Thirty of 52 patients (57.7%) survived and returned to social life. Important factors concerning the prognosis were the severity and grade of cardiac and renal dysfunction, the adjusted support flow rate to enable recovery from circulatory failure, and prevention of circulatory disturbances of the legs and multiple organ failure directly associated with PCPS. With regard to the long-term prognosis of patients treated with PCPS, the readmission rate was 10%, the exacerbation rate was 3.3%, and mortality was 10% during the average follow-up period of 962 days. Optimal management of the mechanical cardiopulmonary support and curative treatment for the myocarditis further improve the outcome of this disease.

PMID 11999637  Circ J. 2002 Feb;66(2):133-44.
著者: Elisabet Witsø, Gustavo Palacios, Ondrej Cinek, Lars C Stene, Bjørn Grinde, Diana Janowitz, W Ian Lipkin, Kjersti S Rønningen
雑誌名: J Clin Microbiol. 2006 Nov;44(11):4095-100. doi: 10.1128/JCM.00653-06. Epub 2006 Aug 30.
Abstract/Text Human enterovirus (HEV) infections can be asymptomatic or cause only mild illness; recent evidence may implicate HEV infection in type 1 diabetes mellitus and myocarditis. Here, we report the molecular characterization of HEV obtained in serial monthly collections from healthy Norwegian infants. A total of 1,255 fecal samples were collected from 113 healthy infants beginning at age 3 months and continuing to 28 months. The samples were analyzed for HEV nucleic acid by real-time PCR. Fifty-eight children (51.3%) had HEV infections. One hundred forty-five positive samples were typed directly by nucleotide sequencing of the VP1 region. HEV-A was detected most frequently, with an overall prevalence of 6.8%. HEV-B was present in 4.8% of the samples and HEV-C in only 0.2% of the samples. No poliovirus or HEV-D group viruses were detected. Twenty-two different serotypes were detected in the study period: the most common were EV71 (14.5%), CAV6 (10.5%), CAV4 (8.9%), E18 (8.9%), and CBV3 (7.3%). These findings suggest that the prevalence of HEV infections in general, and HEV-A infections in particular, has been underestimated in epidemiological studies based on virus culture.

PMID 16943351  J Clin Microbiol. 2006 Nov;44(11):4095-100. doi: 10.112・・・
著者: A B Martin, S Webber, F J Fricker, R Jaffe, G Demmler, D Kearney, Y H Zhang, J Bodurtha, B Gelb, J Ni
雑誌名: Circulation. 1994 Jul;90(1):330-9.
Abstract/Text BACKGROUND: The diagnosis of viral myocarditis remains difficult and generally depends on clinical and histological criteria. Viral cultures and serology are often unrewarding, with low yields. The purpose of this study was to analyze the usefulness of polymerase chain reaction (PCR) in the rapid diagnosis of acute myocarditis in children.
METHODS AND RESULTS: PCR was used to analyze 38 myocardial tissue samples from 34 patients with suspected acute viral myocarditis and 17 control patients with congenital heart disease (14) or hypertrophic cardiomyopathy (3). Myocardial samples were obtained at the time of right ventricular biopsy (13 samples), from explanted hearts (18 samples) at transplantation, and from cardiac autopsy specimens (24 samples) and were evaluated for the presence of enterovirus, cytomegalovirus (CMV), adenovirus, and herpes simplex virus (HSV) using PCR primers designed to consensus and unique sequences of these viral genomes. Blood also was obtained at the time of biopsy (11) or transplant (18). In 26 of 38 myocardial samples (68%), viral genome was detected by PCR (15 adenoviral, 8 enteroviral, 2 HSV, 1 CMV), whereas all control myocardial samples and blood samples were negative. Four patients had positive viral cultures, and these matched the PCR findings. Disagreement with histopathology occurred in 13 of 26 PCR-positive specimens, usually associated with adenovirus.
CONCLUSIONS: PCR offers a rapid, sensitive diagnostic method for myocardial viral infection. While enterovirus is an important etiological agent, adenovirus was more prevalent in this series and should be evaluated when etiology is sought. PCR used in conjunction with standard endomyocardial biopsy appears to enhance the likelihood of detecting viral genome in the myocardium of patients with clinical evidence of myocarditis.

PMID 8026015  Circulation. 1994 Jul;90(1):330-9.
著者: Fiorella Calabrese, Emanuela Rigo, Ornella Milanesi, Giovanni M Boffa, Annalisa Angelini, Marialuisa Valente, Gaetano Thiene
雑誌名: Diagn Mol Pathol. 2002 Dec;11(4):212-21.
Abstract/Text Myocarditis is the most common cause of heart failure in children. We investigated viral etiology of myocarditis/dilated cardiomyopathy (DCM) in children and correlated molecular findings with pathologic and clinical data. Polymerase chain reaction (PCR) or reverse transcription (RT)-PCR were used to analyze 59 endomyocardial biopsies from 48 consecutive young (<18 yrs) patients (pts) with clinical and histologic diagnosis of myocarditis and DCM, employing primers designed to amplify specific sequences of various DNA and RNA viruses. Nucleic acids were successfully extracted in 41 pts and viral genomes were found in 20 (49%): 12 out of 26 pts (46%) with myocarditis, 6 out of 13 (46%) pts with DCM, and both patients with endocardial fibroelastosis. Enteroviruses were more common in DCM (72%), whereas adenoviruses and enteroviruses shared the same rate (36%) in myocarditis. The mumps virus genome was detected in the two pts with endocardial fibroelastosis. More diffuse inflammatory infiltrates and myocyte damage as well as more impaired left ventricular end diastolic volume and shortening fraction were noted in viral positive cases. PCR positive pts had a worse outcome, resulting in transplantation or death. Three out of 8 pts with viral myocarditis who underwent cardiac transplantation had recurrent PCR-proven graft viral infection. Viral myocarditis/DCM appeared to be a more severe disease than nonviral forms. Enteroviruses were more common in DCM, whereas adenoviruses were as frequent as enteroviruses in myocarditis. Persistence of viral infection was associated with disease deterioration. Viral myocarditis relapsed after transplantation.

PMID 12459637  Diagn Mol Pathol. 2002 Dec;11(4):212-21.
著者: J B O'Connell, R E Henkin, J A Robinson, R Subramanian, P J Scanlon, R M Gunnar
雑誌名: Circulation. 1984 Jul;70(1):58-62.
Abstract/Text Current standards for detection of myocarditis in a clinical setting rely on endomyocardial biopsy for accurate diagnosis. With this technique a subset of patients with dilated cardiomyopathy show unsuspected myocarditis histologically. Endomyocardial biopsy, despite its specificity, may lack sensitivity due to sampling error if the inflammation is patchy or focal. Therefore, inflammation-sensitive radioisotopic imaging may be a useful adjunct in the diagnosis of myocarditis. This study was designed to evaluate the applicability of gallium-67 (67Ga) myocardial imaging as an adjunct to endomyocardial biopsy in the diagnosis of myocarditis. Sixty-eight consecutive patients referred for evaluation of dilated cardiomyopathy underwent 71 parallel studies with 67Ga imaging and biopsies that served as the basis of comparison for this study. Histologic myocarditis was identified in 8% of biopsy specimens. Clinical and hemodynamic parameters could not be used to predict the presence of myocarditis. Five of six biopsy samples (87%) with myocarditis showed dense 67Ga uptake, whereas only nine of 65 negative biopsy samples (14%) were paired with equivocally positive 67Ga scans (p less than .001). The single patient with myocarditis and no myocardial 67Ga uptake had dense mediastinal lymph node uptake that may have obscured cardiac uptake. The incidence of myocarditis on biopsy with a positive 67Ga scan was 36% (5/14); however, the incidence of myocarditis with a negative 67Ga scan was only 1.8% (1/57). Follow-up scans for three patients showed close correlation of 67Ga uptake with myocarditis on biopsy. In conclusion 67Ga may be a useful screening test for identifying patients with a high yield of myocarditis on biopsy, and serial scans may eliminate the need for frequent biopsies in patients with proven myocarditis.

PMID 6586327  Circulation. 1984 Jul;70(1):58-62.
著者: A J Morguet, D L Munz, H Kreuzer, D Emrich
雑誌名: Eur J Nucl Med. 1994 Jul;21(7):666-74.
Abstract/Text Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis. This paper discusses the diagnostic potential of scintigraphy in these entities. In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis. Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases. In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings. Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy. In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated.

PMID 7957355  Eur J Nucl Med. 1994 Jul;21(7):666-74.
著者: D M McNamara, W D Rosenblum, K M Janosko, M K Trost, F S Villaneuva, A J Demetris, S Murali, A M Feldman
雑誌名: Circulation. 1997 Jun 3;95(11):2476-8.
Abstract/Text BACKGROUND: Although an autoimmune pathogenesis has been postulated for dilated cardiomyopathy, immunosuppressive therapy has not been shown to be effective in clinical trials. Immune modulatory therapy with immune globulin is an effective therapy for Kawasaki disease in children, and recent data suggest that it improves ventricular function in children with new-onset dilated cardiomyopathies. The role of immune globulin therapy in adults with this disorder has not previously been evaluated.
METHODS AND RESULTS: Ten patients were treated with high-dose intravenous immune globulin infusions (2 g/kg). All were hospitalized with NYHA class III to IV heart failure, left ventricular ejection fraction (LVEF) < 0.40, and symptoms for < 6 months at the time of presentation. One patient died before the completion of therapy. The remaining 9 were discharged, and LVEF was reassessed 12 months after therapy. LVEF improved from 0.24 +/- 0.02 (mean +/- SEM) at baseline to 0.41 +/- 0.04 at follow-up (P = .003). All 9 patients improved functionally to NYHA class I to II, and there have been no subsequent hospitalizations for heart failure during the course of follow-up.
CONCLUSIONS: In this series of patients with new-onset dilated cardiomyopathy treated with high-dose immune globulin, LVEF improved 17 EF units. The effectiveness of intravenous immune globulin therapy in this disorder should be evaluated in a randomized, multicenter trial.

PMID 9184576  Circulation. 1997 Jun 3;95(11):2476-8.

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