Early recognition of life-threatening otolaryngologic complications in pediatric epstein-barr virus infectious mononucleosis: a systematic review and meta-analysis.
- 1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Otorhinolaryngology, Milan, Italy.
- 2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Abstract
Objective
To systematically synthesize evidence on life-threatening otolaryngologic (ENT) complications of pediatric Epstein-Barr virus (EBV) infectious mononucleosis (IM), quantify clinically compatible upper-airway outcomes, assess certainty, and develop a cautious evidence-informed clinical framework.Methods
PubMed/MEDLINE was searched from January 1, 1990 to September 8, 2026 in accordance with PRISMA 2020. Eligible English-language observational studies and case series included at least four patients and reported severe ENT manifestations of EBV-IM. Evidence was classified as direct pediatric when the analyzed cohort was restricted to patients aged ≤18 years and as mixed-age supportive when relevant pediatric/adolescent observations were embedded within a broader age range and could not be fully separated. Mixed-age studies did not contribute to the primary pediatric meta-analysis. Design-specific JBI tools and outcome-level GRADE were used. Quantitative pooling was restricted to studies with clinically compatible populations, denominators, and outcome definitions.Results
Nine studies were included. Clinically significant UAO/airway compromise was the only outcome supporting a narrowly defined meta-analysis. Two directly pediatric hospitalized IM cohorts yielded a REML random-effects pooled proportion of 20.8% (95% CI 7.8-44.9%; I² = 69.1%; τ ² = 0.465; k = 2). Adding one mixed-age cohort in sensitivity analysis yielded 23.2% (95% CI 14.5-35.1%; I² = 38.9%; τ ² = 0.091; k = 3). Suppurative/deep neck complications, candidate warning features, biomarkers, imaging findings, and treatment effects were not pooled because populations, denominator directions, sampling frames, or outcome definitions were incompatible. Certainty was low that UAO is a clinically important complication in hospitalized pediatric IM and very low for the pooled numerical proportion and the remaining evidence streams.Conclusions
UAO is the most consistently documented life-threatening ENT manifestation of pediatric EBV-IM, while suppurative/deep neck complications are clinically important but quantitatively heterogeneous. By separating directly pediatric evidence from mixed-age supportive data and preserving outcome-specific denominators, this review provides a structured synthesis of the limited evidence to support clinical awareness and hypothesis generation, while defining priorities for prospective pediatric validation.
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BibTeX
@article{torretta2026early,
title = {{Early recognition of life-threatening otolaryngologic complications in pediatric epstein-barr virus infectious mononucleosis: a systematic review and meta-analysis.}},
author = {Sara Torretta and Giulia De Lucia and Silvia Cavalera and Lorenzo Cavaleri and Ludovica Battilocchi},
journal = {Frontiers in pediatrics},
year = {2026},
month = oct,
doi = {10.3389/fped.2026.1980308},
url = {https://europepmc.org/article/MED/42923267},
note = {CC BY},
}
RIS
TY - JOUR
TI - Early recognition of life-threatening otolaryngologic complications in pediatric epstein-barr virus infectious mononucleosis: a systematic review and meta-analysis.
AU - Sara Torretta
AU - Giulia De Lucia
AU - Silvia Cavalera
AU - Lorenzo Cavaleri
AU - Ludovica Battilocchi
PY - 2026
DA - 2026/10/08
JO - Frontiers in pediatrics
DO - 10.3389/fped.2026.1980308
UR - https://europepmc.org/article/MED/42923267
AB - Objective To systematically synthesize evidence on life-threatening otolaryngologic (ENT) complications of pediatric Epstein-Barr virus (EBV) infectious mononucleosis (IM), quantify clinically compatible upper-airway outcomes, assess certainty, and develop a cautious evidence-informed clinical framework.Methods PubMed/MEDLINE was searched from January 1, 1990 to September 8, 2026 in accordance with PRISMA 2020. Eligible English-language observational studies and case series included at least four patients and reported severe ENT manifestations of EBV-IM. Evidence was classified as direct pediatric when the analyzed cohort was restricted to patients aged ≤18 years and as mixed-age supportive when relevant pediatric/adolescent observations were embedded within a broader age range and could not be fully separated. Mixed-age studies did not contribute to the primary pediatric meta-analysis. Design-specific JBI tools and outcome-level GRADE were used. Quantitative pooling was restricted to studies with clinically compatible populations, denominators, and outcome definitions.Results Nine studies were included. Clinically significant UAO/airway compromise was the only outcome supporting a narrowly defined meta-analysis. Two directly pediatric hospitalized IM cohorts yielded a REML random-effects pooled proportion of 20.8% (95% CI 7.8-44.9%; I² = 69.1%; τ ² = 0.465; k = 2). Adding one mixed-age cohort in sensitivity analysis yielded 23.2% (95% CI 14.5-35.1%; I² = 38.9%; τ ² = 0.091; k = 3). Suppurative/deep neck complications, candidate warning features, biomarkers, imaging findings, and treatment effects were not pooled because populations, denominator directions, sampling frames, or outcome definitions were incompatible. Certainty was low that UAO is a clinically important complication in hospitalized pediatric IM and very low for the pooled numerical proportion and the remaining evidence streams.Conclusions UAO is the most consistently documented life-threatening ENT manifestation of pediatric EBV-IM, while suppurative/deep neck complications are clinically important but quantitatively heterogeneous. By separating directly pediatric evidence from mixed-age supportive data and preserving outcome-specific denominators, this review provides a structured synthesis of the limited evidence to support clinical awareness and hypothesis generation, while defining priorities for prospective pediatric validation.
SN - 2296-2360
ER -