Optimal Timing for Hen’s Egg Oral Food Challenge in FPIES May Be Age 2 Years

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A study suggested that the optimal timing for a hen’s egg oral food challenge (OFC) among patients with food protein-induced enterocolitis syndrome (FPIES) may be 2 years old, although the optimal timing varies by population.¹

“As well as we know, there is no established consensus regarding the optimal timing of initial OFC in children with hen’s egg FPIES,” wrote investigators, led by Deniz Ilgun Gurel, from the department of pediatric allergy at Hacettepe University School of Medicine in Turkey. “While this timing may vary across populations, our findings suggest that, in our population, an OFC at 24 months is appropriate for assessing tolerance.”

Other studies have reported hen’s egg FPIES remission at a mean of 24.3 months (IQR, 10.7 – 37.9 months) in a Greek population, 25 – 56 months in a Japanese population, a median of 53 months in an Italian population, and 5 years in an Australian population.^2,3,4,5

“Our study demonstrates that hen’s egg OFC for tolerance testing can be performed earlier, but not before 2 years of age,” investigators added.¹

The team retrospectively reviewed hen’s egg oral food challenges at Hacettepe University School of Medicine in Turkey between 2014 and 2024. The study included 46 children (median age, 0.70 years; IQR, 0.57 – 1.02) diagnosed with hen’s egg FPIES; said diagnosis was determined if children vomited 1 – 4 hours after consuming hen’s egg, did not experience IgE-mediated cutaneous and respiratory symptoms, and had ≥ 3 of the following: a second episode of vomiting after eating a hen’s egg, diarrhea, hypotension, hypothermia, severe lethargy, requirement for emergency department admission, and intravenous fluid administration for treatment. The analysis characterized FPIES as mild (< 3 episodes of vomiting without lethargy), moderate (≥ 3 episodes of vomiting with moderate lethargy), and severe (≥ 3 episodes of vomiting with severe lethargy or cyanosis).

As a part of the hen’s egg oral food challenge, children received 3 equal doses of egg, ranging from 0.15 to 3 grams egg white protein/kg, which was cooked for 10 minutes at 45-minute intervals. Investigators sought to assess tolerance development 1 year after the last positive FPIES attack. The observational period was 4 hours after the final dose.

At the initial oral food challenge, 19 children (median age: 24.9 months) had positive results. Children under 24 months had more positive oral food challenges than children over 24 months (62.5% vs 30%; P = .033).

During the second oral food challenge with 15 children (median age, 35.4 months), 26.6% (n = 4) tested positive. Only 3 children (aged 65.3, 81.3, and 108 months) underwent a third oral food challenge, and 2 children underwent a fourth oral food challenge.

Even after 4 oral food challenges, 1 child could still not tolerate hen’s eggs. Investigators observed, for the most part, that the reactions during subsequent oral food challenges were less severe than during earlier challenges.

The age of tolerance development was not linked to hen’s egg SPT (P = .66) or egg-specific IgE positivity (P = .95), multiple FPIES, or the severity of index reaction. A univariate analysis showed that gender, atopic disease, and the number of food triggers did not impact the age a child reached tolerance. The logistic regression analysis demonstrated that undergoing an oral food challenge before 24 months is an independent risk factor for a positive result (odds ratio [OR], 4.82; 95% CI, 1.18 – 19.63; P = .024).

Overall, children developed tolerance, on average, at 27.20 months or 2 years old (IQR, 24 – 33.73 months).

“…our primary objective as pediatric allergists is to assess timely tolerance acquisition, minimizing unnecessary food restrictions and adverse reactions during OFCs,” investigators concluded. “Comprehensive population-specific data are crucial for definitive hen’s egg FPIES OFC recommendations…Given that this study focuses on the Turkish population, there is a need for additional prospective studies conducted across various countries worldwide.”

References

1. Gurel DI, Ocak M, Sekerel B, Sahiner UM, Soyer O. Timing of First Oral Hen’s Egg Challenge in Food Protein Induced Enterocolitis Syndrome. Clin Exp Allergy. 2025 May 27. doi: 10.1111/cea.70086. Epub ahead of print. PMID: 40421545.

2. P. Xepapadaki, N. A. Kitsioulis, E. Manousakis, I. Manolaraki, N. Douladiris, and N. G. Papadopoulos, “Remission Patterns of Food Protein-Induced Enterocolitis Syndrome in a Greek Pediatric Population,” International Archives of Allergy and Immunology 180, no. 2 (2019): 113–119.

3. K. Nishimura, K. Yamamoto-Hanada, M. Sato, et al., “Remission of Acute Food Protein-Induced Enterocolitis Syndrome Confirmed by Oral Food Challenges in Japan,” Nutrients 14, no. 19 (2022): 4158.

4. S. M. Sopo, V. Giorgio, I. Dello Iacono, E. Novembre, F. Mori, and R. Onesimo, “A Multicentre Retrospective Study of 66 Italian Children With Food Protein-Induced Enterocolitis Syndrome: Different Management for Different Phenotypes,” Clinical and Experimental Allergy 42, no. 8 (2012): 1257–1265, https://doi.org/10.1111/j.1365-2222.2012.04027.x.

5. E. Lee, D. E. Campbell, E. H. Barnes, and S. S. Mehr, “Resolution of Acute Food Protein-Induced Enterocolitis Syndrome in Children,” Journal of Allergy and Clinical Immunology. In Practice 5, no. 2 (2017): 486–488.