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DOI: 10.1055/s-2001-11264
Georg Thieme Verlag Stuttgart · New York
Myokarditis im Kindesalter - Forschungsergebnisse einer Dekade
Myocarditis in infancy and childhood. A decade researchPublication History
Publication Date:
31 December 2001 (online)
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Zusammenfassung.
Die Forschungsergebnisse des letzten Jahrzehnts haben uns im pathogenetischen Verständnis der Myokarditis erheblich vorangebracht. Die Virusinfektion des Myokards kann durch das entzündliche Infiltrat kontrolliert werden, die Myokarditis mit geringer oder deutlicher Narbenbildung ausheilen. Daneben wird eine autoimmunvermittelte chronische Myokarditis beobachtet sowie eine Persistenz des Virusgenoms, das mit geringer Replikationsrate den Entzündungsprozess unterhält. Die immunhistochemische Charakterisierung des Infiltrates sowie der molekularbiologische Nachweis von Virusgenom in der Endomyokardbiopsie ermöglichen eine empfindliche Diagnostik der verschiedenen Formen der Myokarditis, nach denen sich auch die Therapie ausrichten sollte. Bisherige Therapiestudien kranken an der mangelhaften ätiologischen Diagnostik, fehlenden Kontrollgruppen oder kleinen Zahlen. Zwei multizentrische Therapiestudien zur immunsuppressiven und antiviralen Therapie mit Interferon bei Kindern und bei Erwachsenen können bei besserer Beteiligung Therapieempfehlungen geben.
The research of the last decade gave new insights in the pathogenesis of viral myocarditis. The virus infection of the myocardium may be controlled by the infiltrating inflammatory cells and heal with more or less scarring. An autoimmune mediated chronic inflammation is observed as well as the persistence of virus genoms, which causes with low replication rate again chronic inflammation. The immunohistochemical characterization of the infiltrating immune cells and the molecular biological proof of virus genoms in endomyocardial specimens allow a sensitive diagnostic of the various forms of myocarditis and should guide therapy. Until now treatment trials did not differentiate between these various forms, had no control groups or very small numbers of patients. Two multicenter treatment trials in Germany referring to immunosuppressive or interferon therapy in children and adults may give - provided a better participation - recommendations for therapy.
Schlüsselwörter
Myokarditis - Kindesalter - Pathogenese - Therapie
Key words
myocarditis - infancy and childhood - pathogenesis - treatment
Literatur
- 01 Akhtar N, Ni J, Stromberg D, Rosenthal G L, Bowles N E, Towbin J A. Tracheal aspirate as a substrate for polymerase chain reaction detection of viral genome in childhood pneumonia and myocarditis. Circulation. 1999; 99 2011-2018
- 02 Arbustini E, Gavazzi A, Dal Bello B, Morbini P, Campana C, Diegoli M, Grasso M, Fasani R, Banchieri N, Porcu E, Pilotto A, Ponzetta M, Bellini O, Lucreziotti S, Vigano M. Ten-years experience with endomyocardial biopsy in myocarditis presenting with congestive heart failure: frequency, pathologic characteristics, treatment and follow-up. G Ital Cardiol. 1997; 27 209-223
- 03 Aretz H AT, Billingham M E, Edwards W D, Factor S M, Fallon J T, Fenoglio J J, Olsen E GJ, Schoen F J. Immunosuppressive therapy of chronic myocarditis in children: Three cases and the design of a randomized prospective trial of therapy. Pediatr Cardiol. 1998; 19 235-239
- 04 Balaji S, Wiles H B, Sens M A, Gillette P C. Immunosuppressive treatment for myocarditis and borderline myocarditis in children with ventricular ectopic rhythm. Br Heart J. 1994; 72 354-359.
- 05 Bastanier C K, Schmaltz A A, Kandolf R, Hofstetter R. Parvo B-19 Infektion des Herzens. Ein ätiologischer Faktor zur Entstehung Dilatativer Kardiomyopathien im Kindesalter?. Z Kardiol. 1999; 88 728
- 06 Billingham M E. Myocarditis and endomyocardial biopsy (letter). Ann Intern Md. 1989; 110 165-166
- 07 Boreda D, Palomera S, Gilbert B, Lienhardt A, deLumley L. 24 cases of human parvovirus B 19 infection in children. Ann Pediatr. 1992; 39 543-549
- 08 Bültmann B, Kandolf R. Persönliche Mitteilung. 1997
- 09 Caforio A LP, Goldmann J H, Haven A J, Saig K M, Dalla Libera L, McKenna W J. Circulating cardiac-specific autoantibodies as markers of autoimmunity in clinical and biopsy-proven myocarditis. Europ Heart J. 1997; 18 270-275
- 10 Camargo P R, Snitcowsky P, da Luz P L, Mazzieri P, Higuchi M L, Rati M, Stolf N, Ebai M, Pileggi F. Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and active myocarditis. Pediatr Cardiol. 1995; 16 61-68
- 11 Chen J M, Spanier T B, Gonzalez J J, Marelli D, Flannery F MA, Tector K A, Cullinane S, Oz M C. Improved survival in patients with acute myocarditis using external pulsatile mechanical ventricular assistance. J Heart Lung Transplant. 1999; 18 351-357
- 12 Chen Y S, Wang M J, Chou N K, Han Y Y, Chiu I S, Lin F Y, Chu S H, Ko W J. Rescue for acute myocarditis with shock by extracorporeal membrane oxygenation. Ann Thorac Surg. 1999; 69 2220-2224
- 13 deSa D J. Isolated myocarditis as a cause of sudden death in the first year of life. Forensic Sci Int. 1986; 30 113-117
- 14 Drucker N A, Colan S D, Leweis A B, Beiser A S, Wessel D L, Takahashi M, Baker A L, Perez-Atayde A R, Newburger J W. γ-globulin treatment of acute myocarditis in the pediatric population. Circulation. 1994; 89 252-257
- 15 Heim A, Stille-Siegener M, Kandolf R, Kreuzer H, Figulla H R. Enterovirus-induced myocarditis: Hemodynamic deterioration with immunosuppressive therapy and successful application of interferon-α. Clin Cardiol. 1994; 17 563-565
- 16 Heim A, Brehm G, Stille-Siegener M, Müller G, Hake S, Kandolf R, Figulla H R. Cultured human myocardial fibroblasts of pediatric origin: natural human interferon-α is more effective than recombinant interferon-α 2a in carrier-state Coxsackievirus B3 replication. J Mol Cell Cardiol. 1995; 27 2199-2208
- 17 Heusch A, Kühl U, Rammos S, Krogmann O N, Schultheiss H-P, Bourgeois M. Complete AV-block in two children with immunohistological proven myocarditis. Eur J Pediatr. 1996; 155 633-636
- 18 Johnsrude C L, Pery J C, Cecchin F, Smith E O, Fraley K, Friedman R A, Towbin J A. Differentiating anomalous left main coronary artery originating from the pulmonary artery in infants from myocarditis and dilated cardiomyopathy by electrocardiogram. Am J Cardiol. 1995; 75 71-74
- 19 Kadirova R, Kartoglu H U, Strebel M P. Clinical characteristics and management of 676 hospitalized diphtheria cases, Kyrgyz Republic, 1995. J lnfect Dis. 2000; 181 110-115
- 20 Kallenberg R, Andelfinger B, Barth H, Frasch W, Harding P, Hussein A, Hofbeck M, Klabus D, Köhler W, Koch A, Lang D, Levin M, Liersch R, Müller-Scholden J, Paul T, Rüdiger H, Sort J, Schulz R, v. Walter J, Wimmer M, Wippermann C F, Schmaltz A A. Myokarditis/DCM im Kindesalter - Bericht über die Registermeidungen für 1994. Z Kardiol. 1995; 84 782
- 21 Kandolf R, Ameis D, Kirschner P, Canu A, Hofschneider P H. In situ detection of enteroviral genomes in myocardial cells by nuclei acid hybridization: an approach to the diagnosis of viral heart disease. Proc Natl Acad Sci USA. 1987; 84 6272-6276
- 22 Kandolf R, Klingel K, Zell R, Sekinka H C, Raab U, Schneider-Brachert W, Bültmann B. Molecular pathogenesis of enterovirus-induced myocarditis: virus persistence and chronic inflammation. Intervirology. 1993; 35 140-151
- 23 Kandolf R, Sauter M, Aepinus C, Schnorr J J, Selinka H-C, Klingel K. Mechanisms and consequences of enterovirus persistence in cardiac myocytes and cells of the immune system. Virus Research. 1999; 62 149-158
- 24 Kececioglu D, Gehrmann J, Mugler M, Rossi R, Vogt J. Myokarditis simuliert akuten Myokardinfarkt im Säuglingsalter. Herz/Kreisl. 1993; 25 353-355
- 25 Killian J G, Kerr K, Lawrence C, Gelermajer D S. Myocarditis and cardiomyopathy associated with clozapine. Lancet. 1999; 354 1841-1845
- 26 Kleinert S, Weintraub R G, Wilkinson J L, Chow C W. Myocarditis in children with dilated cardiomyopathy: incidence and outcome after dual therapy immunosuppression. J Heart Lung Transplant. 1997; 16 1248-1254
- 27 Klingel K, Hohenadl C, Canu A, Albrecht M, Seemann M, Mall G, Kandolf R. Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci USA. 1992; 89 314-318
- 28 Klingel K, Rieger P, Mall G, Selinka H C, Huber M, Kandolf R. Visualization of enteroviral replication in myocardial tissue by ultrastrctural in situ hybridization: identification of target cells and cytopathic effects. Lab lnvest. 1998; 78 1227-1237
- 29 Kodama M, Hanawa H, Zhang S, Saeki M, Koyama S, Hosono H, Miyakita Y, Kathoh K, Inomata T, Izumi T, Shibata A. FK 506 therapy of experimental autoimmune myocarditis after onset of the disease. Am Heart J. 1993; 126 1385-1392
- 30 Kodama M, Zhang S, Hanawa H, Saeki M, Inomata T, Suzuki K, Koyama S, Shibata A. Effects of 15-deoxyspergualin on experimental autoimmune giant cell myocarditis of the rat. Circulation. 1995; 91 1116-1122
- 31 Kyu B S, Matsamori A, Sato Y, Okada J, Chapman N M, Tracy S. Cardiac persistence of cardioviral RNA detected by polymerase chain reaction in a murine model of dilated cardiomyopathy. Circulation. 1992; 86 522-530
- 32 Lauer B, Padberg K, Schultheiss H-P, Strauer B-E. Autoantibodies against human ventricular myosin in sera of patients with acute and chronic myocarditis. J Am Coll Cardiol. 1994; 23 146-153
- 33 Lauer B, Niederau C, Kühl U, Schannwell M, Pauschinger M, Strauer B E, Schultheiss H P. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol. 1997; 30 1354-1359
- 34 Lee K J, McCrindle B W, Bohn D J, Wilson G J, Taylor G P, Freedom R M, Smallhorn J F, Benson L N. Clinical outcomes of acute myocarditis in childhood. Heart. 1999; 82 226-233
- 35 Liu P, Wang E EL, Sole M. Viral myocarditis: Changing concepts in pathogenesis and implications in diagnosis and treatment. Cardiovasc Pathol. 1993; 2 247-257
- 36 Loukoushkina E F, Bobko P V, Kolbasova E V, Kazakova L V, Krasnov V V, Shipova L G, Lazarea T S, Vlasova I N, Schmaltz A A. The clinical picture and diagnosis of diphtheritic carditis in children. Eur J Pediatr. 1998; 157 528-533
- 37 Martin A B, Webber S, Fricker F J, Jaffe R, Demmler G, Kearney D, Zhang Y-H, Bodurtha J, Gelb B, Ni J, Bricker J T, Towbin J A. Acute myocarditis-rapid diagnosis by PCR in children. Circulation. 1994; 90 330-339
- 38 Mason J W, O'Connell J B, Herskowitz A, Rose N R, McManus B M, Billingham M F, Moon T E. A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med. 1995; 333 269-275
- 39 McCarthy R E, Boehmer J P, Hruban R H, Hutchins G M, Kasper E K, Hare J M, Baughman K L. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Eng J Med. 2000; 432 690-695
- 40 McNamara D M, Rosenblum W D, Janosko K M, Trost M K, Villaneuva F S, Demetris A J, Murali S, Feldmann A M. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation. 1997; 95 2476-2478
- 41 Maisch B, Trostel-Soeder R, Stechemesser E, Berg P A, Kochsiek K. Diagnostic relevance of humoral and cell-mediated immune reactions im patients with acute viral myocarditis. Clin Exp Immunol. 1982; 48 533-545
- 42 Maisch B, Hufnagel G, Schönian U, Hengstenberg C. European study of epidemiology and treatment of cardiac inflammatory disease (ESETCID). Eur Heart J. 1996; 16 173-175
- 43 Miric M, Miskovic A, Brkic S, Vasiljevic J, Keserovic N, Pesic M. Long-term follow-up of patients with myocarditis and idiopathic dilated cardiomyopathy after immunomudulatory therapy. FEMS Immun Med Microbiol. 1994; 10 65-74
- 44 Nakagawa M, Sato A, Okagawa H, Kondo M, Okuno M, Takamatsu T. Detection and evaluation of asymptomatic myocarditis in schoolchildren: report of four cases. Chest. 1999; 116 340-345
- 45 Nishio R, Matsumori A, Shioi T, Ishida H, Sasayama S. Treatment of experimental viral myocarditis with interleukin-10. Circulation. 1999; 100 1102-1108
- 46 Pauschinger M, Doerner A, Kuehl U, Schwimmbeck P L, Poller W, Kandolf R, Schultheiss H-P. Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation. 1999; 99 889-895
- 47 Rajs J, Hammarquist F. Sudden infant death in stockholm. A forensic pathology study covering ten years. Acta Paediatr Scand. 1988; 6 712-720
-
48 Rautenburg H W. Klinik und Therapie entzündlicher Herzerkrankungen. In: H. Singer (Hrsg.)
Herzerkrankungen im Kindes- und Jugendalter. Perimed Erlangen; 1989: 172-186 - 49 Saint-Martin J, Bonnaud E, Morinet F, Choulot J J. A Mensire Acute parvovirus myocarditis with fatal outcome. Pediatrie. 1991; 46 597-599
- 50 Schmaltz A A. Die Myokarditis im Kindesalter. Klin Pädiatr. 1991; 203 1-7
- 51 Schmaltz A A, Demel K P, Kallenberg R, Neudorf U, Kandolf R, Klingel K, Bültmann B. Immunosuppressive therapy of chronic myocarditis in children: three cases and the design of a randomized prospective trial of therapy. Pediatr Cardiol. 1998; 19 235-239
- 52 Schowengerdt K O, Ni J, Denfield S W, Gajarski R J, Bowles N P, Rosenthal G, Kearney D L, Price J K, Rogers B B, Schauer G M, Chinnock R E, Towbin J A. Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction. Circulation. 1997; 96 3549-3554
- 53 Schowengerdt K O, Ni J, Denfield S W, Gajarski R J, Radovancevic S, Frazier H O, Demmler G J, Kearney D, Bricker J T, Towbin J A. Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction. J Heart Lung Transplant. 1996; 15 111-123
- 54 Schultheiß H P. Die dilatative Kadiomyopathie - eine chronische Myokarditis? Neue Aspekte zur Diagnostik und Therapie. Z Kardiol. 1993; 82 (Suppl 4) 25-33
- 55 Shah S S, Hellenbrand W E, Gallagher P G. Atrial flutter complicating neonatal coxsackie B2 myocarditis. Pediatr Cardiol. 1998; 19 185-186
- 56 Shanes J G, Ghali J, Billingham M E, Ferrans V J, Fenoglio J J, Edwards W D, Tsai C C, Saffitz J E, Isner J, Furner S, Subramanian R. Interobserver variability in the pathologic interpretation of endomyocardial biopsy results. Circulation. 1987; 75 401-405
- 57 Stiller B, Dähnert I, Wenig Y G, Henning E, Hetzer R, Lange P E. Children may survive severe myocarditis with prolonged use of biventricular assist devices. Heart. 1999; 82 237-240
- 58 Stastny B, Leonhardt-Horti H, Hagel K J, Schranz D. Fulminant diphtheria myxocarditis in an unvaccinated preschool child. Klin Pädiatr. 1999; 6 462-464
- 59 Tomioka N, Kishimoto C, Matsurmori A, Kawai C H. Effects of prednisolone on acute viral myocarditis in mice. J Am Coll Cardiol. 1987; 7 868-872
- 60 Torres F, Anguita M, Gimenez D, Mesa D, Tejero I, Ranco M, Benitez F, Amat M, Valles F. Long-term clinical course of acute myocarditis. prospective study of a series of 99 patients (1987 - 1995). Rev Esp Cardiol. 1996; 49 723-731
Prof. Dr. med. A. A. Schmaltz
Abteilung Pädiatrische KardiologieUniversitätskinderklinik
Hufelandstr. 55
45122 Essen
Phone: Tel. 0201/723-2452
Fax: Fax 0201/723-5743
Email: E-mail: achim.schmaltz@uni-essen.de