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1、临床病理讨论会第1页，共61页，编辑于2022年，星期三A 10 y/o girlChief complaint:Chest discomfort,vomiting and dry cough for one day第2页，共61页，编辑于2022年，星期三Brief HistoryGrowth&development:Weight:22 kg(3rd-10th percentile)Height:130 cm(25-50th percentile)Development milestone:within normal limitPast historyHand-foot-mouth dise
2、ase in 1998Frequent URI and fever during childhoodNo drug or food allergy第3页，共61页，编辑于2022年，星期三Brief HistoryFamily history:Her sister had fever and URI recently.第4页，共61页，编辑于2022年，星期三Present IllnessFever and bilateral hand arthralgia attack once 1 month agoChest discomfort and cough since 9/11 afterno
3、on,2001Visit LMD and URI was toldVomiting and chest tightness on 9/12 0 AM and 5 AM第5页，共61页，编辑于2022年，星期三Present Illness9/12 morning,visit LMD again,ECG showed arrhythmiaRefer to 亞東 hospital第6页，共61页，编辑于2022年，星期三Present IllnessFindings at 亞東 hospital Clear consciousness,ill-looking,pallor appearance,n
4、o cyanosis Irregular heart beat EKG:VPC bigeminy第7页，共61页，编辑于2022年，星期三Present IllnessLab.findings at 亞東 hospital WBC 9000/mm3,Hb 13.5 g/dl BUN 11 mg/dl,Cre 0.6 mg/dl GOT 25 U/L,CK 665 U/L,CK-MB 175 U/L第8页，共61页，编辑于2022年，星期三Present IllnessEchocardiogram at 亞東 hospital Multiple small VSDs,muscular trabe
5、cular type,at apex LV dyskinesia,LVEF 60-70%Mild TR,mild MR第9页，共61页，编辑于2022年，星期三Present IllnessManagement at 亞東 hospital Lidocaine iv drip Dopamine 10 mg/kg/min Refer to NTUH(2pm)第10页，共61页，编辑于2022年，星期三Physical ExaminationPhysical findings at NTUH Consciousness:lethargic,acute ill-looking T/P/R:37/14
6、0/25 BP 80/46 SaO2 97%HEENT:pale conjunctiva anicteric sclera mild cyanotic lip第11页，共61页，编辑于2022年，星期三Physical Examination Neck:jugular venous engorgement Chest:bilateral basal rles Heart:irregularly irregular beats,distant heart sound no murmur第12页，共61页，编辑于2022年，星期三Physical Examination Abdomen:no he
7、patomegaly hypoactive bowel sound Extremities:freely movable cold and cyanotic poor capillary refilling第13页，共61页，编辑于2022年，星期三Initial Lab DataCBC:WBC Hb Hct Plt 8840 12.7 37.2%160 K Seg 82.4%,Lym 13.8%,Eos 0.1%BCS:BUN Cre Na K Cl Ca 12.8 0.63 141 4.5 104 2.41 第14页，共61页，编辑于2022年，星期三Initial Lab DataVBG
8、:pH pCO2 pO2 HCO3 BE 7.36 47.4 27.3 26.9 +1.4Cardiac enzyme:CPK(U/L)CK-MB Troponin I(ng/ml)1040 196.5 31.9CRP:0.53 mg/dl 第15页，共61页，编辑于2022年，星期三Initial Lab DataEKG(9/12):第16页，共61页，编辑于2022年，星期三Initial Lab DataEKG(9/12):第17页，共61页，编辑于2022年，星期三Initial Lab DataEKG(9/12):第18页，共61页，编辑于2022年，星期三Initial Lab D
9、ataEchocardiogram(9/12):LV enlargementLVEF 45%Muscular VSDMild MR,TR,PR 第19页，共61页，编辑于2022年，星期三Echocardiogram(9/12)第20页，共61页，编辑于2022年，星期三Course and TreatmentManagementFor cardiogenic shock:Dopamine,Dobutamin,Primacor,LasixFor ventricular arrhythmia:Amiodarone,Lidocaine,MgSO4For myocarditis:IVIG,Consi
10、der extracorporeal membranous oxygenator(ECMO)support第21页，共61页，编辑于2022年，星期三Course and Treatment9/12 5pm(3 hr after admission)Progressive hypotensionSudden onset of coma,BP drop(pulseless)EKG:ventricular tachycardiaStart CPR(40 min)Start ECMO,transfer to SICU第22页，共61页，编辑于2022年，星期三EKG(9/12,5 PM)第23页，共
11、61页，编辑于2022年，星期三Course in SICUECMO settingV-A ECMO:15 Fr Rt femoral artery,19 Fr Rt femoral vein by cutdownFlow:2000 ml/minMean BP:70 mmHgUrine output:1.72 ml/kg/hr第24页，共61页，编辑于2022年，星期三Echocardiogram(9/13)第25页，共61页，编辑于2022年，星期三Course in SICUVT persistent despite of cardioversion,Lidocaine,Amiodaron
12、e,MgSO4 9/12 9/17:ECMO 5 daysPoor LV functionPersistent lung edema(CXR,clinically)TnI slowly decreaseA-line flatten,no pulsatile wave form第26页，共61页，编辑于2022年，星期三Course in SICUEndomyocardial biopsy(9/14)Mild to moderate perivascular and interstitial lymphocyte infiltrationFoci of myocyte degeneration
13、Interstitial edemaNo giant cell Compatible with acute myocarditis第27页，共61页，编辑于2022年，星期三Course in SICULA drain(9/17):To decompress LV,avoid thrombosisLA dome cannulation connecting to FV cannula ECMO FALAP:22 mmHg 10 mmHg第28页，共61页，编辑于2022年，星期三Echocardiogram(9/17)第29页，共61页，编辑于2022年，星期三Course in SICU9/
14、18,4am Acute thrombosis at LA cannula and ECMO circuit poor flowCPR for 30 min.and emergent re-set ECMO tubing Cons.After CPR:E1M1VTLight reflex(+)第30页，共61页，编辑于2022年，星期三Course in SICU9/19,8am:gross hematuria and ECMO tube thrombosis reset ECMOProgressive dilated pupils,no light reflex,suspected hypo
15、xic encephalopathyRemove ECMO on 9/23(10th day)第31页，共61页，编辑于2022年，星期三Lab data9/129/139/149/159/169/17TnI31.962.41007437.3CK104091242342126759138647026CK-MB196368687403207101Cre0.630.590.560.50.470.51Bil1.240.510.651.361.51.35第32页，共61页，编辑于2022年，星期三Lab Data第33页，共61页，编辑于2022年，星期三Lab DataSerology study;
16、Mycoplasma pneumonia IgM:(9/12)positive,(9/21)negativeOther virology study:all negative Coxsackie A,Coxsackie B1-B6,CMV IgG&IgM,Enterovirus 70,Influenza A&B第34页，共61页，编辑于2022年，星期三Lab DataCulture:Throat swab(9/12):Staphylococcus aureusNasal swab(9/12):Staphylococcus aureus,Viridans streptococciBlood(9
17、/19):Staphylococcus epidermidis第35页，共61页，编辑于2022年，星期三DiscussionDiagnostic approach:Cause of chest pain in childrenIdiopathic:12-45%Costochondritis:9-22%Musculoskeletal trauma:21%Cough,asthma,pneumonia:15-21%Psychogenic factors:5-9%GI disorders:4-7%Cardiac disorders:0-4%第36页，共61页，编辑于2022年，星期三Diagnost
18、ic approachHx:cough,vomitingPE:hypotension jugular venous distention tachycardia irregular heart beat basal rles poor peripheral perfusion Cardiovascular compromise 第37页，共61页，编辑于2022年，星期三Diagnostic approachFlu-like illness,arrhythmia,cardiovascular compromise Acute myocarditis highly suspectedD/D:Di
19、lated cardiomyopathy Anomalous left coronary artery Chronic tachyarrhythmia Pericarditis 第38页，共61页，编辑于2022年，星期三Diagnostic approachEKG:VPC bigeminy,ventricular tachycardiaST-segment changeElevated cardiac enzymeEchocardiogram:marked LV dyskinesiaEndomyocardial biopsyLymphocyte infiltrationMyocyte deg
20、eneration Acute myocarditis confirmed第39页，共61页，编辑于2022年，星期三Clinical classification of myocarditisFulminantAcuteChronic activeChronic persistentInitial presentationShock,severe LV dysfuntionCHFCHFNormal LV functionEndomyocardial biopsyMultifocal active myocarditisActive or borderline myocarditisActiv
21、e or borderline myocarditisActive or borderline myocarditisNature historyComplete recovery or deathIncomplete recovery or DCMDCMNormal LV function第40页，共61页，编辑于2022年，星期三Myocarditis:an enigmatic disease!第41页，共61页，编辑于2022年，星期三Dark side of the myocarditisInitial non-specific symptoms Difficult to establ
22、ish the diagnosisEtiology hard to findComplexity of pathogenesisOften refractory to conventional treatment第42页，共61页，编辑于2022年，星期三Dark side of the myocarditisInitial non-specific symptoms Similar to patients with sepsis,bronchiolitis,pneumonia,gastroenteritis,hepatitis,and renal failure etc.Aggressive
23、 fluid resuscitation may harm unstable patientsRapid progression in fulminant myocarditis第43页，共61页，编辑于2022年，星期三Dark side of the myocarditisDifficult to establish the diagnosisLimited sensitivity and specificity of changes in CXR,ECG,cardiac enzyme(Troponin level:more sensitive)Echocardiogram:LV dysf
24、unction,often regionalEndomyocardial biopsy:as gold standard,but sensitivity 3-63%第44页，共61页，编辑于2022年，星期三Dallas criteriaBorderline myocarditisActive myocarditisAm J Cadiovasc Pathol 1987;1:3-14第45页，共61页，编辑于2022年，星期三Dark side of the myocarditisEtiology hard to findVIRAL CAUSESEnterovirus Coxsackie A C
25、oxsackie B Echovirus PoliovirusAdenovirus Cytomegalovirus Herpesvirus Influenza A Epstein-Barr virusVaricella Mumps Measles Parvovirus Rabies Hepatitis B,C Rubella Rubeola Respiratory syncytial virus Human immunodeficiency virusRickettsial Rickettsia ricketsii Rickettsia tsutsugamushiBacterial Menin
26、gococcus Klebsiella Leptospira Mycoplasma Salmonella Clostridia Tuberculosis Brucella Legionella pneumophila smallpox Streptococcus Protozoal Trypanosoma cruzi Toxoplasmosis Amebiasis Other parasites Toxocara canis Schistosomiasis Hetereophyiasis Cysticercosis Echinococcus Visceral larva migrans Tri
27、chinosis Fungi and yeasts Actinomycosis Coccidiodomycosis Histoplasmosis Candida NONVIRAL CAUSES 第46页，共61页，编辑于2022年，星期三Dark side of the myocarditisEtiology hard to findToxic Scorpion Diphtheria Drugs Sulfonamides Phenylbutazone Cyclophosphamide Neomercazole Acetazolamide Amphotericin B Indomethacin
28、Tetracycline Isoniazid Methyldopa Phenytoin PenicillinHypersensitivity/Autoimmune Rheumatoid arthritis Rheumatic fever Ulcerative colitis Systemic lupus erythematosus Mixed connective tissue disease Scleroderma Whipples disease Other Sarcoidosis Kawasaki disease CornstarchNONINFECTIOUS ETIOLOGIES第47
29、页，共61页，编辑于2022年，星期三Dark side of the myocarditisEtiology hard to findPediatr Cardiol 2001;22:34-9第48页，共61页，编辑于2022年，星期三Dark side of the myocarditisComplexity of pathogenesisNEJM 2000;343:1388-98第49页，共61页，编辑于2022年，星期三Dark side of the myocarditisComplexity of pathogenesis Factors contributing to host s
30、usceptibilityAutoantibodies:to adenosine nucleotide translocator,myosinExpression of cell adhesion molecules(ICAM-1)Expression of coxsackie-adenovirus receptor(CAR)第50页，共61页，编辑于2022年，星期三Dark side of the myocarditisOften refractory to conventional treatmentStandard therapy:ACE inhibitor,inotropic age
31、nts,diuretics often not effective in fulminant myocarditisImmunosuppression:IVIG,steroids,cyclosporin still controversial第51页，共61页，编辑于2022年，星期三Bright side of the myocarditisGood long term prognosis of fulminant myocarditisImprovement of mechanical support:LVAD,BVAD,ECMO第52页，共61页，编辑于2022年，星期三Bright s
32、ide of the myocarditisGood long term prognosis of fulminant myocarditisNEJM 2000;342:690-5第53页，共61页，编辑于2022年，星期三Bright side of the myocarditisGood long term prognosis of fulminant myocarditis第54页，共61页，编辑于2022年，星期三Bright side of the myocarditisGood long term prognosis of fulminant myocarditisWhy?Diff
33、erent viral agent?Different host response?Autoimmune in nature?第55页，共61页，编辑于2022年，星期三Bright side of the myocarditisVentricular assistant device(VAD)&Extracorporeal membrane oxygenation(ECMO)第56页，共61页，编辑于2022年，星期三Bright side of the myocarditisVAD and ECMO in fulminant myocarditis:Basically a reversib
34、le diseaseIndications:-Failing medical treatment(inotropic requirement with poor perfusion)-Cardiac arrest第57页，共61页，编辑于2022年，星期三Bright side of the myocarditisOutcome of VAD and ECMO used in fulminant myocarditis:J Thorac Cardiovasc Surg.2001;112:440-8第58页，共61页，编辑于2022年，星期三Future strategiesAntiviral
35、agents:interferon,ribavirin,pleconarilVaccine:to specific virus,T-cell receptors,tolerance to myosinEarlier mechanical supportMore specific immunosuppression:OKT3,NO synthetase blocker,第59页，共61页，编辑于2022年，星期三Clinical diagnosisFulminant myocarditis,possible viral origin,etiology?Cause of death:ECMO dysfunction,Hypoxic-ischemic encephalopathy secondary to circulatory collapseMyocarditis in recovery?第60页，共61页，编辑于2022年，星期三Thanks for your attention!第61页，共61页，编辑于2022年，星期三