A Systematic Review Incorporating Meta-Analysis on the Effectiveness of Intravenous Immunoglobulin Versus Corticosteroids in the Treatment of Pediatric Myocarditis


Intravenous immunoglobulin
Pediatric myocarditis
Left ventricular ejection fraction
Mortality rate
Heart transplantation




Background: Concerns have been raised about the efficacy of intravenous immunoglobulin and corticosteroids in pediatric myocarditis; however, the relationship between the risk and efficacy of these two therapies in children with myocarditis varies. Methods: A systematic review on seventeen studies was conducted in July 2020, which included 1,960 subjects at the baseline, with 788 receiving intravenous immunoglobulin and 142 receiving corticosteroids. The mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the prognostic role of both treatments using dichotomous and continuous methods with random or fixed-effect models. Results: The use of intravenous immunoglobulin was significantly associated with a lower mortality rate or heart transplantation in children with myocarditis (OR, 0.55; 95% CI, 0.40-0.77, p < 0.001) compared with the control group. However, corticosteroids were not significantly associated with the same parameters (OR, 0.72; 95% CI, 0.31-1.63, p = 0.43). The use of intravenous immunoglobulin was not significantly related to improving left ventricular ejection in children with myocarditis (OR, 2.30; 95% CI, -9.65-14.25, p = 0.71) and so were corticosteroids (MD, 5.17; 95% CI, -0.26-10.60, p = 0.06). Conclusion: The use of intravenous immunoglobulin might have an independent risk relationship with a lower mortality rate or heart transplantation and is recommended in children with myocarditis to prevent complications.


Cooper Jr LT, 2009, Myocarditis. N Engl J Med, 360(15): 1526-1538.

Rose NR, 2009, Myocarditis: Infection Versus Autoimmunity. J Clin Immunol, 29(6): 730-737.

D’Ambrosio A, Patti G, Manzoli A, et al., 2001, The Fate of Acute Myocarditis Between Spontaneous Improvement and Evolution to Dilated Cardiomyopathy: A Review. Heart, 85(5): 499-504.

Matsuura H, Ichida F, Saji T, et al., 2016, Clinical Features of Acute and Fulminant Myocarditis in Children–2nd Nationwide Survey by Japanese Society of Pediatric Cardiology and Cardiac Surgery. Circ J, 80(11): 2362-2368.

O’Connell JB, Robinson JA, Henkin RE, et al., 1981, Immunosuppressive Therapy in Patients with Congestive Cardiomyopathy and Myocardial Uptake of Gallium-67. Circulation, 64(4): 780-786.

Rose NR, 2016, Viral Myocarditis. Curr Opin Rheumatol, 28(4): 383.

McNamara DM, Holubkov R, Starling RC, et al., 2001, Controlled Trial of intravenous Immune Globulin in Recent-Onset Dilated Cardiomyopathy. Circulation, 103(18): 2254-2259.

Hia CPP, Yip WCL, Tai BC, et al., 2004, Immunosuppressive Therapy in Acute Myocarditis: An 18-Year Systematic Review. Arch Dis Child, 89(6): 580-584.

Foerster SR, Canter CE, Cinar A, et al., 2010, Ventricular Remodeling and Survival Are More Favorable for Myocarditis Than for Idiopathic Dilated Cardiomyopathy in Childhood: An Outcomes Study from the Pediatric Cardiomyopathy Registry. Circ Heart Fail, 3(6): 689-697.

Drucker NA, Colan SD, Lewis, A.B., et al., 1994, Gamma-Globulin Treatment of Acute Myocarditis in the Pediatric Population. Circulation, 89(1): 252-257.

Prasad AN, Chaudhary S, 2014, Intravenous Immunoglobulin in Children with Acute Myocarditis and/or Early Dilated Cardiomyopathy. Indian Pediatr, 51(7): 583-584.

Heidendael JF, Den Boer SL, Wildenbeest JG, et al., 2018, Intravenous Immunoglobulins in Children with New Onset Dilated Cardiomyopathy. Cardiol Young, 28(1): 46-54.

Bhatt GC, Sankar J, Kushwaha K, 2012, Use of Intravenous Immunoglobulin Compared with Standard Therapy Is Associated with Improved Clinical Outcomes in Children with Acute Encephalitis Syndrome Complicated by Myocarditis. Pediatr Cardiol, 33(8): 1370-1376.

Yen MH, Huang YC, Chen MC, et al., 2015, Effect of Intravenous Immunoglobulin for Neonates with Severe Enteroviral Infections with Emphasis on the Timing of Administration. J Clin Virol, 64: 92-96.

Haque A, Bhatti S, Siddiqui FJ, 2009, Intravenous Immune Globulin for Severe Acute Myocarditis in Children. Indian Pediatr, 46(9): 801-811.

Stroup DF, Berlin JA, Morton SC, et al., 2000, Meta-Analysis of Observational Studies in Epidemiology: A Proposal for Reporting. JAMA, 283(15): 2008-2012.

Moher D, Liberati A, Tetzlaff J, et al., 2009, Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med, 6(7): e1000097.

Gupta A, Das A, Majumder K, et al., 2018, Obesity Is Absolutely Associated with Increased Risk of Hepatocellular Cancer–related Mortality. Am J Clin Oncol, 41(9): 874-881.

O’Neil ME, Cheney TP, Hsu FC, 2020, Exploration of Risk of Bias Elements and Assessment Methods, in Pharmacologic and Nonpharmacologic Treatments for Posttraumatic Stress Disorder: An Update of the PTSD-Repository Evidence Base, Agency for Healthcare Research and Quality, US.

Higgins JP, Thompson SG, Deeks JJ, et al., 2003, Measuring Inconsistency in Meta-Analyses. BMJ, 327(7414): 557-560.

Klugman D, Berger JT, Sable CA, et al., 2010, Pediatric Patients Hospitalized with Myocarditis: A Multi-Institutional Analysis. Pediatr Cardiol, 31(2): 222-228.

Kim HJ, Yoo G-H, Kil HR, 2010, Clinical Outcome of Acute Myocarditis in Children According to Treatment Modalities. Korean J Pediatr, 53(7): 745.

Butts RJ, Boyle GJ, Deshpande SR, et al., 2017, Characteristics of Clinically Diagnosed Pediatric Myocarditis in a Contemporary Multi-Center Cohort. Pediatr Cardiol, 38(6): 1175-1182.

Ghelani SJ, Spaeder MC, Pastor W, et al., 2012, Demographics, Trends, and Outcomes in Pediatric Acute Myocarditis in the United States, 2006 to 2011. Circ Cardiovasc Qual Outcomes, 5(5): 622-627.

Kishimoto C, Shioji K, Hashimoto T, et al., 2014, Therapy with Immunoglobulin in Patients with Acute Myocarditis and Cardiomyopathy: Analysis of Leukocyte Balance. Heart Vessels, 29(3): 336-342.

Atiq M, Hoda M, Aslam N, 2014, Effect of Intravenous Gamma Globulin on Short- and Mid-Term Clinical Outcome in Acute Viral Myocarditis in Children. World J Cardiovasc, 4(2): 42803.

English RF, Janosky JE, Ettedgui JA, et al., 2004, Outcomes for Children with Acute Myocarditis. Cardiol Young, 14(5): 488.

Camargo PR, Snitcowsky R, Da Luz PL, et al., 1995, Favorable Effects of Immunosuppressive Therapy in Children with Dilated Cardiomyopathy and Active Myocarditis. Pediatr Cardiol, 16(2): 61-68.

Aziz KU, Patel N, Sadullah T, et al., 2010, Acute Viral Myocarditis: Role of Immunosuppression: A Prospective Randomized Study. Cardiol Young, 20(5): 509-515.

Heart Failure Society of America, 2010, Section 16: Myocarditis: Current Treatment. J Card Fail, 16(6): e176-e179.

Pollack A, Kontorovich AR, Fuster V, et al., 2015, Viral Myocarditis – Diagnosis, Treatment Options, and Current Controversies. Nat Rev Cardiol, 12(11): 670-680.

Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, et al., 2001, Randomized, Placebo-Controlled Study for Immunosuppressive Treatment of Inflammatory Dilated Cardiomyopathy: Two-Year Follow-Up Results. Circulation, 104(1): 39-45.

Frustaci A, Russo MA, Chimenti C, 2009, Randomized Study on the Efficacy of Immunosuppressive Therapy in Patients with Virus-Negative Inflammatory Cardiomyopathy: The TIMIC Study. Eur Heart J, 30(16): 1995-2002.

Lu C, Qin F, Yan Y, et al., 2016, Immunosuppressive Treatment for Myocarditis: A Meta-Analysis of Randomized Controlled Trials. J Cardiovasc Med, 17(8): 631-637.

Maisch B, Alter P, 2018, Treatment Options in Myocarditis and Inflammatory Cardiomyopathy. Herz, 43(5): 423-430.

Robinson J, Hartling L, Vandermeer B, et al., 2020, Intravenous Immunoglobulin for Presumed Viral Myocarditis in Children and Adults. Cochrane Database Syst Rev, 19(8): CD004370.

Amabile N, Fraisse A, Bouvenot J, et al., 2006, Outcome of Acute Fulminant Myocarditis in Children. Heart, 92(9): 1269-1273.

Liu C, Chen J, Liu K, 2005, Immunosuppressive Treatment for Inflammatory Cardiomyopathy. Int Heart J, 46(1): 113-122.

Madney YM, Fathy M, Elberry AA, et al., 2019, Aerosol Delivery Through an Adult High-Flow Nasal Cannula Circuit Using Low-Flow Oxygen. Respir Care, 64(4): 453-461.