Biphasic reactions in children undergoing oral food challenges
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Updated: May 11, 2026

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Published on: May 31, 2021
Juhee Lee1, Jackie P-D Garrett, Terri Brown-Whitehorn
1Division of Allergy and Immunology, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.
Insights
Biphasic reactions after pediatric food challenges are rare (1.5%). While clinical features showed no significant differences, severe initial reactions and specific treatments may indicate a higher risk for biphasic reactions.
Area of Science:
- Pediatric Allergy and Immunology
- Clinical Immunology
- Food Allergy Research
Background:
- Biphasic reactions, a recurrence of allergic symptoms after initial improvement, are not well-documented in children.
- Understanding biphasic reactions is crucial for managing food allergy and oral food challenges (OFCs).
Purpose of the Study:
- To determine the prevalence of biphasic reactions in children undergoing OFCs.
- To identify clinical and treatment factors associated with biphasic reactions in pediatric food allergy.
Main Methods:
- Retrospective chart review of oral food challenges (OFCs) conducted between July 2007 and March 2011.
- Analysis of charts for 48 hours post-challenge to identify biphasic reactions.
- Comparison of clinical features and treatments between uniphasic and biphasic reaction groups.
Main Results:
- A biphasic reaction rate of 1.5% (9 out of 614 positive challenges) was observed.
- Biphasic reactions occurred in challenges involving eggs, peanuts, and milk, with symptom-free intervals of 2-24 hours.
- While not statistically significant, biphasic reactions were associated with initial anaphylaxis, multiple organ involvement, and treatments like steroids, epinephrine, and antihistamines.
Conclusions:
- Biphasic reactions are uncommon in children undergoing OFCs but may be linked to more severe initial allergic responses.
- A 24-hour observation period may be beneficial for children experiencing severe allergic reactions during OFCs.
Abstract:
Literature regarding biphasic reactions in the pediatric population is sparse. We aimed to determine the prevalence of biphasic reactions in children with food allergies undergoing oral food challenges (OFCs) and examine whether any clinical or treatment factors are associated with biphasic reactions. A retrospective chart review of OFCs conducted between July 2007 and March 2011 was performed. Charts were reviewed from time of challenge to 48 hours after challenge to capture data on any biphasic reactions. Uniphasic and biphasic reactions were compared in terms of specific clinical features and treatments. Of 614 positive challenges, 9 resulted in a biphasic reaction (1.5%). Six of the biphasic reactions occurred in challenges where the initial reaction met anaphylaxis criteria. The biphasic reactions were to eggs (4), peanuts (3), and milk (2). The symptom-free interval ranged from 2 to 24 hours. There were no statistically significant differences in clinical features between uniphasic and biphasic reactions, but there appeared to be a higher percentage of initial reactions with multiple organ involvement and meeting anaphylaxis criteria in the biphasic group. Biphasic reactors were significantly more likely to have received steroids for their initial reaction. A higher percentage of biphasic reactors also appeared to have received epinephrine, multiple doses of epinephrine, and antihistamines for their initial reactions. Biphasic reactions are rare in children undergoing OFCs and may be associated with more severe allergic reactions. Children with severe reactions may benefit from a 24-hour period of observation.
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