Biphasic anaphylaxis in children presenting to emergency departments: incidence, risk factors, timing, and implications for observation periods; a systematic review

Abstract

Background: Biphasic anaphylaxis complicates observation decisions in pediatric emergency departments because of the variations in recurrence definitions, clinical severity, and timing. This review examined incidence, associated factors, recurrence timing, and implications for observation. Methods: PubMed, Scopus, and Web of Science were searched for studies published between 2000 and 2026. Two authors independently screened studies involving children with emergency department anaphylaxis. Findings were synthesized narratively according to PRISMA 2020; heterogeneity in definitions, denominators, and ascertainment precluded pooling. Results: Seven studies were included, five retrospective cohorts and two quality improvement studies. Reported recurrence proportions ranged from 1.7% to 14%, although the highest estimate included exacerbations after partial recovery. Clinically important recurrence requiring epinephrine occurred in 0.3% of one cohort. Delayed reactions reported up to 33 hours after resolution, whereas one cohort recorded all treatment-requiring recurrences within four hours of treatment initiation. Lower systolic pressure, pallor or hypotonia, intravenous fluids, and greater initial severity were associated with recurrence in unadjusted comparisons. Observation pathways reduced hospitalization from 28.5% to 11.2% and low-risk admission from 49% to 7%, without increased recorded revisits. Conclusions: Findings support risk-stratified observation while distinguishing true biphasic anaphylaxis from persistent symptoms. Four-hour observation cannot exclude delayed recurrence. Standardized definitions, explicit timing origins, and active post-discharge follow-up are needed to clarify recurrence risk and evaluate observation strategies across pediatric age groups and clinical settings in children.