What is the evidence for IVIG for treating viral myocarditis in pediatrics?

What is the evidence for IVIG for treating viral myocarditis in pediatrics?

Comment by InpharmD Researcher

There is a lack of robust data to determine whether intravenous immunoglobulin (IVIg) use in the pediatric patient population for treatment of acute viral myocarditis is safe and efficacious. In general, data in the adult population suggests IVIg may lengthen survival time, though evidence is low-certainty. In the pediatric population, findings are predominantly limited to observational studies and case reports, with a varying number of doses administered, regimens utilized, and heterogeneous baseline characteristics.

Background

A 2025 systematic review evaluated the efficacy and safety of intravenous immunoglobulin (IVIg) in the treatment of acute viral myocarditis in children by exploring randomized controlled trials (RCTs). A literature search was conducted across five databases, including PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science, along with trial registries and grey literature sources. Despite identifying 9,524 records initially, none met the eligibility criteria as RCTs focusing on the pediatric population with acute viral myocarditis. The review underscored the urgent need for well-designed prospective randomized trials to substantiate the role of IVIg in managing acute viral myocarditis in children; previous reviews and studies included in broader analyses had methodological limitations, such as combining adult and pediatric data or relying on quasi-randomized designs, which do not provide the rigorous evidence necessary for clinical recommendations. [1]

A 2020 Cochrane review examined the efficacy and outcomes of IVIg for presumed viral myocarditis in both the adult and pediatric patient population. In general, however, included trials provide very low certainty evidence, and only one pediatric trial was included, with very low-certainty evidence for all evaluated outcomes. Pediatric patients were randomized to 1 g/kg IVIg or placebo for two days, then received echocardiography 1 and 6 months after randomization to determine evidence of left ventricular end-diastolic diameter (LVEDD) or left ventricular shortening fraction (LVSF). No differences were observed between groups in survival after six months following IVIg administration, nor improvement in LVEDD and LVSF after six months. No data for safety, hospitalization, complete recovery, left ventricular ejection fraction (LVEF) improvement, or functional capacity were reported. These limited outcomes underscore a need for more robustly designed studies to elucidate the precise benefit-risk calculus of the IVIg. [2]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What is the evidence for IVIG for treating viral myocarditis in pediatrics?

Level of evidence

D - Case reports or unreliable data Read more→

Please see Tables 1-2 for your response.

Pediatric Patients Hospitalized with Myocarditis: A Multi-Institutional Analysis
Design	Nonconcurrent cohort study N= 427,615 (total discharges), 216 diagnosed with myocarditis
Objective	To identify the patient, institutional, and utilization characteristics associated with outcome in hospitalized pediatric patients with myocarditis
Study Groups	Myocarditis patients (n= 216)
Inclusion Criteria	Pediatric discharges from birth through age 21 years from participating hospitals between January 1, 2005, and December 31, 2005
Exclusion Criteria	Not specified
Methods	Analysis of the Pediatric Health Information System (PHIS) dataset, examining patient-level, institution-level, and utilization variables. Procedures and medications were determined by ICD 9 diagnosis codes. Statistical analyses included chi-square tests and logistic regression
Duration	January 1, 2005, to December 31, 2005
Outcome Measures	Survival
Baseline Characteristics		Survived (N = 199)	Died (N = 17)
	Age 0-30 days	11 (5.5%)	1 (5.9%)
	Age 31-365 days	32 (16.1%)	1 (5.9%)
	Age 1-5 years	62 (31.2%)	8 (47.1%)
	Age 6-12 years	32 (16.1%)	6 (35.3%)
	Age 13-18 years	61 (30.7%)	1 (5.9%)
	Female	116 (58.3%)	6 (35.3%)
	Caucasian	122 (61.3%)	11 (64.7%)
	Severity score - Minor	48 (24.1%)	0 (0.0%)
	Severity score - Moderate	53 (26.6%)	0 (0.0%)
	Severity score - Major	61 (30.7%)	7 (41.2%)
	Severity score - Extreme	37 (18.6%)	10 (58.8%)
Results		Survived (n= 199)	Died (n= 17)	Odds ratio	P-value
	ECMO	9 (4.5%)	7 (41.2%)	14.8	<0.05
	Milrinone	85 (42.7%)	12 (70.6%)	3.2	<0.05
	Epinephrine	64 (32.2%)	12 (70.6%)	5.1	<0.05
	Dopamine	61 (30.7%)	12 (70.6%)	5.4	<0.05
	Lidocaine	81 (40.7%)	12 (70.6%)	3.5	<0.05
Adverse Events	Not specified
Study Author Conclusions	Pediatric patients with myocarditis have considerable variability in their presentations and outcomes, use more resources, and die more often than children with other diagnoses. IVIG use did not impact survival, even in patients with extreme illness scores.
Critique	The study provides a comprehensive multi-institutional analysis, which is a strength, but relies on administrative data that may not capture all clinical nuances. The lack of prospective, randomized trials limits the ability to draw definitive conclusions about the efficacy of treatments like IVIG. The study's retrospective nature and reliance on coding accuracy are limitations.

References:
[1] [1] Klugman D, Berger JT, Sable CA, He J, Khandelwal SG, Slonim AD. Pediatric patients hospitalized with myocarditis: a multi-institutional analysis. Pediatr Cardiol. 2010;31(2):222-228. doi:10.1007/s00246-009-9589-9

Pediatric Myocarditis Management With Dual Immunotherapy: A Case Report Highlighting IVIG and Methylprednisolone Efficacy
Design	Case report
Case presentation	A 12-month-old female infant, who had a recent history of an upper respiratory tract infection, presented with symptoms including fever, tachypnea, lethargy, and poor feeding. Initial workup revealed significant cardiac dysfunction, confirmed by laboratory tests showing elevated cardiac enzymes and echocardiography revealing moderate left and right ventricular impairment alongside other indicators of acute cardiac dysfunction. Clinical management involved the administration of intravenous immunoglobulin (IVIG) at a dose of 2 grams/kg over 48 hours, complemented by a tapering regimen of methylprednisolone starting at 10 mg/kg daily. The treatment initiated with supportive measures such as supplemental oxygen and inotropic support via dopamine. A marked clinical improvement followed the dual immunotherapy, with the patient demonstrating enhanced ventricular function as evidenced by echocardiographic findings. By day 7, the ejection fraction improved to 29%, and the patient was weaned off inotropic support by day 5. The patient was discharged on day 10 with a prescription for oral carvedilol and captopril to assist ongoing cardiac function and prevent further myocardial remodeling. During a five-month follow-up, the patient remained asymptomatic with normalized biomarker levels, though some residual indicators of myocardial remodeling persisted.
Study Author Conclusions	The synergistic immunomodulatory effects of IVIG and systemic corticosteroids are of particular interest in pediatric myocarditis, especially in cases of suspected immune-mediated inflammation or viral myocarditis accompanied by a heightened inflammatory response. IVIG is believed to modulate the immune system, while corticosteroids offer potent anti-inflammatory action that may reduce myocardial injury. In the present case, dual immunotherapy was associated with significant clinical improvement. While marked clinical improvement was observed in this case following combined treatment with IVIG and methylprednisolone, it is important to acknowledge that this is a single case report. As such, causality cannot be definitively established, and the findings may not be generalizable without support from larger, controlled clinical studies.

References:
[1] [1] Owdat AI Sr, Alhajieh A, Alsheab R, et al. Pediatric Myocarditis Management With Dual Immunotherapy: A Case Report Highlighting IVIG and Methylprednisolone Efficacy. Cureus. 2025;17(6):e86073. Published 2025 Jun 15. doi:10.7759/cureus.86073