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1 Original Article 대한소아응급의학회지 2015 제 2 권제 2 호 Pediatric Emergency Medicine Journal Volume 2, Number 2, December, 2015 소아심근염에대한임상적고찰 변종번 이현정 이흔지 이정원 유병대 전덕호 순천향대학교의과대학응급의학교실 A clinical review of acute myocarditis in children Jong Beon Byun, M.D., Hyun Jung Lee, M.D., Heun Ji Lee, M.D., Jung Won Lee, M.D., Byeong Dae Yoo, M.D., Duck Ho Jun, M.D. Department of Emergency Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea Purpose: The aims of this study are to document our single-center experience with pediatric acute myocarditis and to investigate its clinical features and outcomes. Methods: We performed a retrospective chart review of all children aged <16 years who were diagnosed with acute myocarditis between January 2006 and January We analyzed the following data: initial symptoms, laboratory findings, treatment, and outcomes. We divided patients into two groups according to severity. Results: Twenty-nine patients were diagnosed with acute myocarditis. Thirteen patients (45%) survived to discharge, 4 patients (14%) died, and 12 patients (41%) who required extracorporeal membrane oxygenation were transferred. There was no significant age-related differences in the incidence of myocarditis between children <12 months (45%) and those >12 months (55%) of age. The overall incidence of upper respiratory tract infection symptoms was 69%; general symptoms, 66%; cardiac symptoms, 24%; gastrointestinal symptoms, 17%; and neurologic symptoms, 10%. Twelve patients (41%) had cardiomegaly. Ten patients had electrocardiographic abnormalities (tachycardia, ST changes, T wave changes, and low voltage). Echocardiographic abnormalities were pericardial effusion or impaired contractility. Severe group consisted of 13 patients who were either transferred or died and contained more patients with cardiomegaly and electrocardiogram abnormalities, but this was statistically irrelevant. Most patients had elevated concentrations of cardiac biomarkers, but the median concentrations were not statistically different between the 2 groups. Main treatment modalities included antibiotics (90%), inotropics (59%), and intravenous immunoglobulin (76%). Conclusion: Definite diagnostic criteria for acute myocarditis do not exist, so misdiagnosis can occur. Extracorporeal membrane oxygenation therapy for severe cases is available only in some hospitals, so proper treatment can be delayed. Further evaluation of the current situation regarding acute myocarditis will contribute towards proper treatment. Key Words: Child; Myocarditis; Prognosis; Extracorporeal Membrane Oxygenation; Review Corresponding Author Hyun Jung Lee Department of Emergency Medicine, Soonchunhyang University College of Medicine, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Korea Tel: Fax: silenos@schmc.ac.kr 서론 급성심근염은심근의염증, 괴사, 근세포의용해의소견을보이는질환으로소아에서완전회복되기도하지만, 많은수에서좌심실기능부전, 심부전, 전도장애등의후 81
2 대한소아응급의학회지제 2 권제 2 호 2015 유증을초래하거나사망에이르기도한다 1). 발생은산발적이거나유행성을보이고계절이나지리적인조건에따라변동이있을수있다 2,3). 캐나다에위치한 3차의료기관의후향적인연구에따르면, 한해응급의료센터로내원하는 10,000명당약 0.5명의유병률을보인다고보고하였다 4). 또다른연구에서는한해 100,000명당 1명의유병률을보인다고보고하였다 5). 소아심근염의발생률을예측하는것은어려운데, 이는심근염을진단하는데있어민감도나특이도가높은검사가없기때문이다. 그로인해확진이어려운경우가많다. 소아심근염의경우초기에증상만으로진단을내리기어렵고, 발생률이낮은질환이지만, 증상이갑자기악화되어사망에이르는소아의중증응급질환중의하나이고주로응급실로내원하는경우가많으므로, 응급실에서소아를진료하는의료인은심근염의가능성을늘염두에두어야한다. 그동안소아응급환자의대부분은중증도가낮기때문에중증질환에대한관심이부족했고, 이로인해발병률이낮은심근염의경우빠른진단과치료가늦어지거나소아의치료시설이부족하여적절한치료를받지못해사망에까지이르는경우들이발생해왔다. 또한, 우리나라에서소아에서의심근염에대한연구는낮은발병률로인해현재까지도보고가많지않다. 현재국내에서는중증소아심근염환자들은일부대형병원에서만최종치료가가능하며, 관련연구또한최종치료가가능한일부대형병원환자들에대한현황과치료결과로만보고되고있다. 따라서, 최근소아응급환자에대한전문적인치료에대해사회적관심이높아지고있으며, 이에발병률은낮으나중요한소아의중증질환인심근염에대해소아전용응급실을운영중인순천향대학교천안병원의현황을고찰해보고자한다. 대상과방법 2006년 1월부터 2015년 1월까지본원에내원하였고심근염상병 ( 주상병또는부상병 ) 으로검색된환자를대상으로의무기록의후향적분석을통해연구를진행하였다. 의무기록진단명에서처음에검색된환자는총 47명이었으며, 팔로네증후과거력이있던 1명과단순가슴통증이나호흡곤란을주소로내원하여검사를진행하였으나심근염의가능성이떨어져퇴원한 9명은제외하였다. 또한초기증상이심근염으로의심되어입원하였다가퇴원당시진단명이바뀐 6명은제외하였으며, 그중 2명은입원후가와사키병으로최종진단되었다. 입원당시시행한심초음파에서심방중격결손이나심실중격결손과같은구조적이 상이발견된 2명도제외하였다. 이를통해최종적으로선택된환자는총 29명이었으며, 이들은신체검진, 단순흉부방사선사진, 심초음파, 심전도검사, 검사실검사등을토대로소아청소년과심장전문의에의해최종진단되었다. 임상증상으로는심장증상으로심계항진및가슴통증을증상의범주로포함하였고, 호흡기증상으로호흡곤란, 기침, 가래, 콧물을포함하였다. 또한, 소화기증상으로구역, 구토, 설사, 복통을포함하였고, 전신증상으로는발열, 무기력, 보챔을포함하였으며, 여기서발열의정의는 37.5 C를넘는것으로정의하였다. 신경증상으로는발작, 의식소실을포함하였다. 심전도의변화는정상동리듬, 빈맥, ST파변화, T파변화, 저전압소견을보였으며, 단순흉부방사선사진의경우정상, 심비대, 폐침윤소견을보였다. 심비대는 12개월이상의경우심흉비 (CT ratio) 가 50% 이상 12개월미만의경우심흉비가 60% 이상으로각각정의하였다. 심초음파의결과는정상, 심장막삼출, 수축력감소로분류하여분석하였다. 검사실검사중 creatine kinase (CK), CK-MB, troponin T, pro-brain natriuretic peptide (pro- BNP), aspartate aminotransferase (AST) 를분석하였고, 본원에서의정상치를통해정상과상승한경우로분류하였다. Pro-BNP의경우 Nelson textbook of pediatrics 18th edition에나와있는참고치를사용하여, 500 pg/ml 이상인경우를상승으로정의하였다. 심근염이의심되는모든경우에서혈액및소변배양검사를시행하였으며, 호흡기증상이주증상인경우에는바이러스중합효소연쇄반응및미코플라스마검사를추가로시행하였다. 미코플라스마검사의경우양성반응은면역글로불린 M이양성으로보인경우로정의하였다. 중증도에따라경증군과중증군으로나누었다. 경증군은본원에서입원후끝까지치료하여완쾌된환자군으로, 중증군은본원에서치료도중사망하였거나, 치료도중증상악화로인해체외막산소공급치료가필요하나본원에서불가하여타병원으로전원시킨경우를중증군으로설정하였다. 중증도에따른분류에서전원환자의경우는최종치료결과를알수는없지만체외막산소공급치료가필요한것만으로도중증도가높다고판단하여분류하였고, 또한사망한경우도사망결과만으로도중증도가높다고판단되었기때문에같은군으로분류하였다. 두군사이의성별, 임상증상, 단순흉부방사선사진소견, 검사실검사결과, 심전도및심초음파소견등을종합하여분석하였다. 데이터는 IBM SPSS ver (IBM Co., Armonk, NY, USA) 을이용하여분석하였다. 통계방법으로성별, 82 Pediatric Emergency Medicine Journal
3 소아심근염에대한임상적고찰 연령, AST, CK-MB, troponin T, 단순흉부방사선사진, 심전도검사의경우 Fisher exact test를이용하여분석하였고, CK의경우 chi-square test를이용하여분석하였다. 각군간 CK, CK-MB, troponin T, pro-bnp, AST의수치를 Mann-Whitney test를통해비교분석하였다. 내원형태는응급실을통한환자가 24명 (83%), 외래를통한경우가 5명 (17%) 이었다. 내원시나타났던증상중에서는호흡기증상이 20명 (69%) 으로가장많았고, 다음으로전신증상 19명 (66%), 심장증상 7명 (24%), 소화기증상 5명 (17%), 신경증상 3명 (10%) 순이었다. 21명 (71%) 의환자는 2가지이상의증상을호소하였다. 전신증상을나타낸 19명중 12명이발열을호소하였다 (Table 1). 결 과 2. 소아심근염환자의검사소견 1. 소아심근염환자의일반적특성심근염으로내원한 29명의환자중 21명 (72%) 이남자였고, 여자는 8명 (28%) 이었다. 치료결과를보면총 29명중입원하여후유증없이퇴원한환자는 13명 (45%), 본원에서사망한환자는 4명 (14%), 입원후병세악화로체외막산소공급치료가필요하나본원에서는불가하여타병원으로전원된환자가 12명 (41%) 이었다. 평균입원일수는 4.1일이었으며, 중환자실재원일수는평균 2.3일이었다. 재원형태로는중환자실입원이 17명, 일반병실에서치료한경우는 7명, 응급실에서검사중전원된환자는 5명이었다. 사망환자 4명은모두빠르게증상이악화되어, 입원당일과 2병일에각각 2명이사망하였다. 환자의연령은 12개월미만에서 13명 (45%), 12개월이상에서 16명 (55%) 으로연령에따른차이없이고르게발생하는경향을보였다. 이들의연령의중앙값 ( 사분위수범위 ) 는 3.0 ( ) 이었다. 단순흉부방사선사진에서정상소견을보인환자가 14명 (48%), 심비대를보인환자가 12명 (41%), 폐침윤을보인환자는 3명 (11%) 이었다. 심전도검사에서나타난이상소견으로는빈맥, ST파변화, T파변화, 저전압의변화가있었다. 전체 29명의환자중 22명에서심전도검사를시행하였고, 정상동리듬을보인환자가 9명 (41%) 으로가장많았으며, 빈맥 6명 (27%), ST파변화 4명 (18%), T파변화 2명 (10%), 저전압 1명 (4%) 로나타났다 (Table 2). 심초음파의경우 29명의환자중 24명에서시행하였으며, 정상, 심장막삼출, 수축력감소의세가지의형태로나타났다. 이중심장막삼출을보인환자가 11명 (46%), 수축력감소가 9명 (38%), 정상 4명 (16%) 이었다 (Table 3). 심근표지자검사 (CK, CK-MB, troponin T, pro- BNP) 에서는 CK의경우검사를시행한 28명중 16명 (57%) 에서상승된소견을보였고, CK-MB의경우 29명중 24명 (83%), troponin T의경우 29명중 17명 (59%), pro-bnp의경우 29명중 3명을제외한 26명 (90%) 에서 Table 1. Clinical characteristics of the patients (n=29) Variable No. (%) Age (yr), median (interquartile range) 3.0 (0 9.5) Sex, male 21 (72)0. Chief complaints* Cardiac symptoms 7 (24). Respiratory symptoms 20 (69)0. Gastrointestinal symptoms 5 (17). Systemic symptoms 19 (66)0. Neurologic symptoms 3 (10). Two or more symptoms 21 (72)0. *Cardiac symptoms included chest pain, palpitation; respiratory symptoms included dyspnea, fever, cough, sputum, rhinorrhea; gastrointestinal symptoms included nausea, vomiting, diarrhea, abdominal pain; systemic symptoms included fever, lethargy, irritability; neurologic symptoms included convulsion, loss of consciousness. Table 2. Electrocardiogram features in patients with myocarditis (n=22) Variable No. of patients (%) Normal sinus rhythm 9 (41) Tachycardia 6 (27) ST change 4 (18) T wave change 2 (9)0 Low voltage 1 (5)0 Table 3. Echocardiography in patients with myocarditis (n=24) Variable No. of patients (%) Normal 04 (17) Pericardial effusion 11 (46) Decreased contractility 09 (37) Pediatric Emergency Medicine Journal 83
4 대한소아응급의학회지제 2 권제 2 호 pg/ml 이상으로상승된소견을보였다. 각심근표지자의중앙값 ( 사분위수범위 ) 은각각, AST는 53.5 ( ), CK는 ( ), CK-MB는 45.5 ( ), troponin T는 0.18 ( ), pro- BNP는 7,484.5 (1, ,000.0) 이었다 (Table 4). 3. 중증도에따른두군의결과비교중증도가다른두군을비교분석하였다. 총 29명의환자중연고지관계또는병실부족으로 3명이전원되었는데, 이들은치료결과를알수없어분석에서제외하였다. 따라서중증도에따른비교분석에서는총 26명을분석하였고, 경증군이 13명, 중증군이 13명이었다. 두군간성별의차이가있는지를비교하였고, 경증군은남자가 10명 (77%), 중증군은남자가 8명 (62%) 으로두군간의성별의차이는없었다. 12개월미만의환자와 12개월이상의환자사이에중증도의차이가있는지를비교분석하였다. 12개월미만의환자 13명중 9명 (69%) 이중증군이었고, 12개월이상의환아 13명중 9명 (69%) 이경증 군이었다. 이처럼 12개월미만의환자에서높은중증도와관련이있는것으로나타났으나, 통계학적의미는없었다. 단순흉부방사선사진의심비대유무를비교해보았을때, 경증군에서는심비대가있는경우가 13명중 3명 (23%) 이었고, 중증군에서는 13명중 8명 (62%) 으로경증군에비해많은환자에서보였으나통계학적의미는없었다. 두군간심전도의이상을비교하였을때, 경증군에서는 13명중 11명에서심전도를시행하였고, 11명중 5명 (45%), 중증군에서는 8명중 5명 (63%) 에서비정상심전도소견 ( 저전압또는 ST분절변화또는 T파이상 ) 을보였으나통계학적의미는없었다. 검사실검사에서 AST 상승은경증군에서 10명 (77%), 중증군에서 10명 (77%), CK 상승은경증군에서 7명 (54%), 중증군에서 8명 (62%), CK-MB 상승은경증군에서 12명 (92%), 중증군에서 10명 (77%), troponin T 상승은경증군에서 6명 (46%), 중증군에서 9명 (69%), pro- BNP 상승은경증군에서 12명 (92%), 중증군에서 11명 (85%) 으로비슷한양상을보였으나통계학적의미는없었다 (Table 5). Table 4. Laboratory results in patients with myocarditis (n=29) Variable (reference range) No. of elevation (%) Median (interquartile range) AST (0 40 IU/L) 23 (79) 53.5 ( )000. Creatine kinase ( IU/L) 16 (57) ( )00. Creatine kinase-mb (0 24 U/L) 24 (83) 45.5 ( )000. Troponin T (0 0.1 ng/ml) 17 (59) 0.18 ( )000. Pro-BNP (0 500 pg/ml) 26 (90) 7,484.5 (1, ,000.0) AST: aspartate aminotransferase, pro-bnp: pro-brain natriuretic peptide. Table 5. Characteristics between group A and group B Variable* Group A (mild group; n=13) Group B (severe group; n=13) P value Sex, male 10 (77) 08 (62) Age (mo), < (31) 09 (69) Chest X-ray, cardiomegaly 03 (23) 08 (62) Electrocardiogram (n=19), abnormal 05 (45) 05 (63) AST, elevation (0 40 IU/L) 10 (77) 10 (77) Creatine kinase, elevation ( IU/L) 07 (54) 08 (62) Creatine kinase-mb, elevation (0 24 U/L) 12 (92) 10 (77) Troponin T, elevation (0 0.1 ng/ml) 06 (46) 09 (69) Pro-BNP, elevation (0 500 pg/ml) 12 (92) 11 (85) Values are presented as number (%). *Laboratory results are presented with the reference ranges. Electrocardiogram group A (n=11) group B (n=8). AST: aspartate aminotransferase, pro-bnp: pro-brain natriuretic peptide. 84 Pediatric Emergency Medicine Journal
5 소아심근염에대한임상적고찰 검사실검사에서두군간의중앙값 ( 사분위수범위 ) 을비교하였다. AST는경증군에서 53.0 ( ), 중증군에서 54.0 ( ) 이었고, CK는경증군에서 ( ), 중증군에서 (89.5-1,689.5) 이었으며, troponin T는경증군에서 0.07 ( ), 중증군에서 0.33 ( ) 으로나타났다. CK-MB는경증군에서 38.0 ( ), 중증군에서 61.0 ( ) 이었고, pro-bnp는경증군에서 4,894.0 (2, ,497.0), 중증군에서 35,000.0 ( ,000.0) 으로나타났다. Pro-BNP가상승하지않았던 3명중 2명은경증군이었고, 내원당일검사상각각 pg/ml, pg/ml이었으나다음날재검사에서는각각 pg/ml, 3,499.0 pg/ml으로상승하였다. 나머지 1명은중증군으로내원당일검사상 pg/ml이었으나, 다음날사망하여재검사를시행하지못하였다 (Table 6). 바이러스중합효소연쇄반응은 29명의환자중 13명에서시행하였으며 (45%), 그중 6명에게양성반응이나왔다 (46%). 원인바이러스로는메타뉴모바이러스, B형인플루엔자바이러스, 리노바이러스, 아데노바이러스, 호흡기세포융합바이러스가확인되었다. 미코플라스마검사는 29 명의환자중 14명에서시행하였으며 (48%), 그중 6명 (43%) 에서양성반응을보였다. 4. 치료및경과 29명중 26명에게항생제를투여했으며 (90%), 불안정한혈류역학적변화를보인 17명에게승압제를투여하였다 (59%). 또한, 22명에게면역글로불린을투여하였다 (76%). 본원에서입원후회복된환자는총 13명으로, 평균재원일수는 11.5일이었고, 중환자실재원일수는 4.2일이었고, 12 명에서퇴원후외래진료가시행되었으며, 모두후유증없이회복되었다. 호흡성혹은대사성산증이있으면서심한호흡곤란을호소한 6명에서는기관내삽관이시행되었다. 고찰 심근염은심근세포의염증으로정의되고, 그원인으로는세균, 진균, 기생충등의원인이있으나바이러스가가장흔한것으로알려져있다 6). 바이러스심근염의원인으로콕사키B바이러스가가장흔하고, 아데노바이러스, 파르보바이러스 B19, 엡스타인-바바이러스, 거대세포바이러스, 인간헤르페스바이러스 6 등도보고되고있다 7). 심근염은증상이모호한경우가많고, 정확한유병률은잘알려져있지않으며초기내원당시에는다른질환과감별이힘든경우가많다 6). 미국에서시행된 Pediatric Health Information System (PHIS) 데이터분석에서남자의비율이전체의약 66% 를차지한다고보고하는등급성심근염에관한대부분의보고에서도남자의발병률이좀더높게나온것으로나타났다 8-10). 본연구에서도남자의비율이높았는데 (72%), 이러한결과는여자에게있어호르몬의방어효과에기인한것이라는보고도있다 11). 또한 19세이하를대상으로한 PHIS 보고에서심근염으로진단된환자들의평균연령은 9.2세였으며, 6개월에서 12개월사이와 14세에서 17세사이에집중되어있는이봉성의양상을나타내는것으로보였다 12). 본연구에서환자들의 IQR은 3.0 ( ) 이었으며, 이봉성의결과를보이지는않았다. 이는본원에서기준으로설정한연령이만 15세였기때문인것으로보이며, 12개월미만의환자가 13명 (45%) 으로절반가까운비율을보였다. 임상증상은연령과감염의급 만성여부에따라다르다. 신생아는열, 심부전, 호흡곤란, 청색증등의증상을보이며바이러스간염, 무균성뇌수막염, 발진등이동반될수있고, 전격적으로진행되는경우증상시작 1-7일내에사망할수도있다. 연장아에서간혹급성심부전의증상을나타내는경우도있으나, 주로서서히진행하는심부전이나갑자기발생한부정맥으로발현한다. 일부에서는급성감염때는모르게지나가고확장형심근병증으로병 Table 6. Comparison of laboratory results between group A and group B Variable (reference range) Group A (mild group; n=13) Group B (severe group; n=13) P value AST (0 40 IU/L) 53.0 ( ) ( ) Creatine kinase ( IU/L) ( ) ( ) Creatine kinase-mb (0 24 U/L) 38.0 ( ) ( ) Troponin T (0 0.1 ng/ml) ( ) ( ) Pro-BNP (0 500 pg/ml) 4,894.0 (2, ,497.0) 35,000.0 ( ,000.0) Values are presented as median (interquartile range). AST: aspartate aminotransferase, pro-bnp: pro-brain natriuretic peptide. Pediatric Emergency Medicine Journal 85
6 대한소아응급의학회지제 2 권제 2 호 2015 원에오게된다. 바이러스감염의전구증상인발열이나근육통, 호흡기나소화기증상이전통적으로심근염과동반된다고알려져있으나, 발표된전구증상은 10-80% 까지다양하게나타나는것으로보고되었다 13). 유럽의한연구에서, 급성혹은만성심근염이의심되는 3,055명을대상으로연구를진행한결과 72% 에서는호흡곤란을보였고, 32% 에서는가슴통증을호소하였으며, 18% 에서는부정맥을나타냈다 14). 본연구에서주로호흡기증상이우세한것으로나타났는데, 이는국내에서발표된심근염에관한연구결과와대체로일치한다 1,6,15,16). 심근표지자검사에서초기에는소수의환자에서만상승이되어있지만, 진단에도움을주는것으로알려져있다. 그중에서도 troponin I에서높은특이도 (89%) 를보인다고보고된연구도있었고, 또급성심근염에서 troponin T의상승이 CK-MB의상승보다빈번하게나타난다고보고되기도하였다 17,18). 본연구에서는환자의대부분이내원당시심근표지자 (CK, CK-MB, troponin T, pro-bnp, AST) 의상승을보였는데, CK의경우검사를시행한 29 명중 16명 (57%), CK-MB의경우 29명중 24명 (83%), troponin T의경우 29명중 17명 (59%), pro-bnp의경우 29명중 26명 (90%), 마지막으로 AST의경우 29명중 23명 (79%) 에서상승된소견을보였다. 그러나심근표지자의상승은검사당시병의지속시간과연관이있고, 상승이나타나지않은경우도있으므로, 정상소견을보인다고해서심근염을배제할수는없다. 미코플라스마와심근염의연관성에대해국내에서사례보고가있었다 19). 미코플라스마의경우주로소아에서호흡기증상으로발현되어편도염이나기관지염, 비전형폐렴과같은호흡기질환을일으키는것으로알려져있으나, 드물게급성심근염이나심막염을일으키기도하며, 혈액검사에서감염이확인된환자에서 % 까지나타나는것으로보고되고있다 20-22). 본연구에서는 14명에서미코플라스마검사를시행하였고, 그중 6명 (43%) 에서양성을보였다. 그러나우리나라의경우어릴때부터집단생활로인해감염의빈도가높고감염후혈액검사양성을나타내는기간이최대 2년까지도지속되는것으로보고되고있으므로, 미코플라스마감염이심근염의직접적인인과관계는명확하지않다. 따라서관련된연구가좀더필요할것으로보인다. 급성심근염에서의심전도는비전형적인 ST분절의변화나 T파의변화를동반한동성빈맥을보인다. 때때로, ST분절의상승이나하강, 병적 Q파의발현등이나타나기도해서급성심근경색으로오인하는경우도발생한다는연구보고가있다 23). 또한심전도의민감도는 47% 이지만, Q파혹은좌각차단이심장이식이나높은사망률과연관성이있는것으로보고되었다 9,23-25). 심초음파검사에서는수축력감소, 심비대, 심장막삼출과방실판막역류등과같은소견을관찰할수있다. 또한, 도플러초음파를이용하여제한성의양상과전반적인심실운동장애소견을보이는경우생존율이저하되는결과를얻었고, 이를통해좌심실의부전의예후를예측하는지표로활용한연구보고도있었다 26). 본연구에서는후향적인분석방법으로인해심초음파소견에자세한분류및분석이이루어지지않아결과를도출할수없었다는한계가있었다. 심근염의확진에는, Dallas criteria 에의거하여심근생검이필요하다 4). 비록이진단기준이심근염의진단에중요하지만심근생검은민감도가낮은단점이있으며, 일부보고에의하면임상적으로심근염이의심되는환자 2,000명에서단지 200명만이 Dallas criteria에부합했다고한다. 심근염진단의민감도가낮은원인으로는, 표준화된임상적기준이없으며, 진단시조직을얻는데실패하는경우가많고, 특히심근염이국소적으로국한되어있는경우에병변을놓칠수있으며, 광학현미경만을진단기준으로정하는단점등이보고되고있다 27). 최근심근생검에관한 American Heart Association 및 American College of Cardiology, European Society of Cardiology에서의지침은 2가지정도로요약해볼수있다 28). 첫째, 전격성심근염이나거대세포심근염의양상을보이는경우 class I recommendation을하고있다. 둘째, 경과 2주이전에원인이설명되지않고, 새롭게발생한심부전이정상혹은좌심실의확장과함께혈역학적인변화를가져오는전격성의양상을띄는경우시행해야하며, 2 주에서 3개월에걸친설명되지않고, 새롭게발생한심부전이좌심실의확장과더불어심실부정맥이나 2도혹은 3 도방실차단이동반되는경우나거대세포심근염이의심되는환자에서 1-2주간의치료에도반응을보이지않는환자에서시행해야한다고권고하고있다. 하지만이러한양상을보이지않는심근염환자에대한생검의역할에대해서는아직까지확립된바가없다 23). 본원에서는퇴원한환자의경우도 2주이상입원한환자가 3명밖에없었으며, 사망한 4명의경우 2일이내, 증상이악화되어전원된환자의경우 2주이내에이루어져심근생검은시행되지않았다. 심근염의치료에대한핵심은좌심실부전에대한보존적치료이다. 그이유는대부분의환자들이바이러스감염이발생한후수주뒤에급성심근염으로진단이되기때 86 Pediatric Emergency Medicine Journal
7 소아심근염에대한임상적고찰 문인데, 따라서항바이러스제의사용의경우큰효과를얻기힘들다. 하지만, 인터페론베타의경우만성적이고안정적인확장성심근증환자에서효과가높았다는연구보고가있다 29). 정맥면역글로불린의투여에대해서는실험모델과무작위사례연구에서항바이러스효과및면역조절작용이있는것으로나타나실제로도효과가있을것으로추측을하였으나, 실제심근염및급성심근증환자를대상으로한연구들에서정맥면역글로불린을투여한군이위약을투여한군과비교했을때큰차이가없다는보고도있다 30). 국내에서도 2010년에 3개대학병원합동으로시행한면역글로불린의투여효과에대한연구에서, 위의결과처럼면역글로불린이임상적호전과는큰관련이없는것으로보고하였다. 본원에서도대부분의경우 (76%) 에서면역글로불린의투여가이루어졌지만, 치료효과에관련해서는좀더연구가필요할것으로보인다 15). 본연구의한계점은다음과같다. 첫번째, 후향적인방법으로인해차트에누락이되어있는정보를반영할수없었다. 두번째, 검사가체계적으로시행되지못했다. 세 번째, 치료도중전원된환자가많아통계학적으로의미있는결과가나오기힘들었다는점에서한계점이있다. 하지만, 중증의소아심근염의경우대형의료기관및소아심장치료전문기관을제외하고는최종치료가이루어지지못하는경우가많으므로, 본연구는대부분의 2, 3차의료기관의실제적인현황을반영하고있을것으로생각된다. 중증소아응급질환인심근염환자의좀더정확한현황파악과체계적인진단및치료를위해여러의료기관의통합적인연구가필요하다. 결론적으로, 유병률이낮고중증도가높은특성을가지고있는급성심근염을확진하는것은현실적으로어렵기때문에, 진단을놓치기쉽다. 또한, 진단이되고난후에도증상이악화되는상황에서체외막산소공급치료의경우특정대형병원에서만가능하므로이를해소할수있는방안에대한강구가필요할것으로보인다. 특히, 효율성의측면만으로치료기회가줄어드는상황은피해야할것이다. 소아심근염환자의보다정확한현황파악과체계적인진단및치료를위해더많은연구가필요하다. REFERENCES 01. Lee HM, Kim MS, Jo DS, Kim JS, Joo CU. Clinical manifestations and prognosis of acute myocarditis in children. J Korean Pediatr Cardiol Soc 2006;10: Mounts AW, Amr S, Jamshidi R, Groves C, Dwyer D, Guarner J, et al. A cluster of fulminant myocarditis cases in children, Baltimore, Maryland, Pediatr Cardiol 2001;22: Strikas RA, Anderson LJ, Parker RA. Temporal and geographic patterns of isolates of nonpolio enterovirus in the United States, J Infect Dis 1986;153: Freedman SB, Haladyn JK, Floh A, Kirsh JA, Taylor G, Thull-Freedman J. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics 2007;120: Levine MC, Klugman D, Teach SJ. Update on myocarditis in children. Curr Opin Pediatr 2010;22: Kwon BS, Lee CH, Choi EY, Lee JH, Jin SM, Bae EJ, et al. Acute myocarditis in children: clinical aspects and outcomes. J Korean Pediatr Cardiol Soc 2005;9: Canter CE, Simpson KP. Diagnosis and treatment of myocarditis in children in the current era. Circulation 2014;129: Caforio AL, Calabrese F, Angelini A, Tona F, Vinci A, Bottaro S, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 2007; 28: Magnani JW, Danik HJ, Dec GW Jr, DiSalvo TG. Survival in biopsy-proven myocarditis: a long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J 2006;151: Mason JW, O Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, et al. A clinical trial of immunosuppressive therapy for myocarditis: the myocarditis treatment trial investigators. N Engl J Med 1995;333: Schwartz J, Sartini D, Huber S. Myocarditis susceptibility in female mice depends upon ovarian cycle phase at infection. Virology 2004;330: Ghelani SJ, Spaeder MC, Pastor W, Spurney CF, Klugman D. Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to Circ Cardiovasc Qual Outcomes 2012;5: Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation 2006;113: Hufnagel G, Pankuweit S, Richter A, Schonian U, Maisch B. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID): first epidemiological results. Herz 2000;25: Kim HJ, Yoo GH, Kil HR. Clinical outcome of acute myocarditis in children according to treatment modalities. Korean J Pediatr 2010;53: Pediatric Emergency Medicine Journal 87
8 대한소아응급의학회지제 2 권제 2 호 Lee EY, Lee HL, Kim HT, Lee HD, Park JA. Clinical features and short-term outcomes of pediatric acute fulminant myocarditis in a single center. Korean J Pediatr 2014;57: Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin I associated with myocarditis: experimental and clinical correlates. Circulation 1997;95: Lauer B, Niederau C, Kuhl U, Schannwell M, Pauschinger M, Strauer BE, et al. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol 1997; 30: Kim DI, Choi JH, Cho EY, Choi YJ, Sung JY, Yang MA, et al. A Case of fatal myocarditis associated with mycoplasma pneumoniae pneumonia. Korean J Pediatr Infect Dis 2009; 16: Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev 2004; 17: Paz A, Potasman I. Mycoplasma-associated carditis: case reports and review. Cardiology 2002;97: Waites KB. New concepts of mycoplasma pneumoniae infections in children. Pediatr Pulmonol 2003;36: Cooper LT Jr. Myocarditis. N Engl J Med 2009;360: Nakashima H, Katayama T, Ishizaki M, Takeno M, Honda Y, Yano K. Q wave and non-q wave myocarditis with special reference to clinical significance. Jpn Heart J 1998;39: Morgera T, Di Lenarda A, Dreas L, Pinamonti B, Humar F, Bussani R, et al. Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes. Am Heart J 1992;124: Chung BY, Chung NS, Ha JW, Rim SJ, Ahn SK, Choi DH, et al. Clinical features and prognosis according to the left ventricular function in the patients with acute myocarditis. J Korean Soc Echocardiogr 1999;7: McKenna WJ, Davies MJ. Immunosuppression for myocarditis. N Engl J Med 1995;333: Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 2007;50: Kuhl U, Pauschinger M, Schwimmbeck PL, Seeberg B, Lober C, Noutsias M, et al. Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 2003;107: McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001;103: Pediatric Emergency Medicine Journal
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