New Data Backs Use of Milk and Egg Ladders in Severe IgE-Mediated Food Allergies

A case series shows the safety and efficacy of the 5-step milk ladder and 4-step egg ladder in building tolerance among children at high risk with severe immunoglobulin E (IgE)-mediated cow’s milk and hen’s egg allergies.1

“This retrospective case-series of 29 children…. provided evidence that the 5- [milk ladder] and the 4- [egg ladder] may be safe and effective way of reintroducing milk and egg,” investigators led by Daria Wiszniewska, from the Medical University of Warsaw in Poland, wrote.1

The cow’s milk ladder was developed for children with mild to moderate non-IgE-mediated cow’s milk allergy. Its use in children with IgE-mediated cow’s milk allergy is still debated.

Currently, ladders access tolerance development in children with IgE-mediated food allergies who have experienced mild, non-anaphylactic reactions. More recently, literature suggests cow’s milk and hen’s egg ladders may also be safe for children with more severe allergic symptoms, although this remains controversial.2

Investigators conducted a single-center case series to evaluate the safety and effectiveness of the 5-step milk ladder and 4-step egg ladder in high-risk children with IgE-mediated cow’s milk and hen’s egg allergies in real-world settings.1 The primary outcome was treatment success, defined as a negative oral food challenge with raw pasteurized/modified milk (120 mL) or a soft-boiled/lightly scrambled egg. Secondary outcomes included tolerance to baked milk and egg in a muffin, negative food challenges at each step, use of epinephrine or other medications, failure to introduce tested foods, and egg yolk tolerance in children who did not achieve full egg tolerance.

The team recruited 29 children (62% males) in the department of pediatrics at the Medical University of Warsaw, from January 2022 to August 2024. Children had a mean age of 36.14 months (range, 8 – 106 months), mean body weight of 14.05 kg, height of 93.22 cm, and body mass index of 15.85 kg/m2.

Among the sample, 4 children had IgE-mediated cow’s milk allergy, 10 with hen’s egg allergy, and 15 sensitized to both. Food allergy was confirmed by either a positive oral food challenge, specific IgE, skin prick test results, or a component-resolved diagnostic test.

“High-risk” was defined as having a history of asthma, anaphylaxis, severe allergic symptoms, high sIgE (≥ kUA/L for milk and 7 kUA/L for egg), or a large skin prick test (>8 mm for milk and >7 mm for egg). Children with FPIES were excluded.

The first step of the food ladder—tolerance acquisition to baked cow’s milk or egg proteins—was assessed via oral food challenge using a muffin. For the 5-step milk ladder, children ate 1.5 muffins (25 mL of milk per muffin). In the 4-step egg ladder, they had 1 – 3 muffins (3 months = 1 egg). The first step was supervised in-hospital; the rest at home.

The 5-step milk ladder progressed to pancake/crepe (fried milk; 1.5 pancake), hard cheese (fresh or baked; 15 – 30 grams), yogurt (1/4 – ½ cup), and pasteurized or modified milk (120 – 240 mL). The 4-step egg ladder progressed to pancake/crepe (1 – 3), hard-boiled egg or well-cooked eggs/ French toast (1), and soft-boiled or lightly scrambled eggs (1).

Among 15 children, 5 (33%) tolerated raw cow’s milk proteins and 11 (73%) tolerated baked cow’s milk (muffins). It took 6 to 34 months (mean, 16 months) following the first oral food challenge to develop milk tolerance, with 80% able to consume raw milk in < 18 months.

Moreover, among 23 children allergic to egg, 3 (13%) developed tolerance to any form of egg after 11 – 17 months following the first oral food challenges. In total, 17 (74%) tolerated baked egg in the form of muffins, 11 (48%) tolerated pancakes, and 8 (35%) tolerated hard-boiled egg or well-cooked scrambled eggs.

During treatment, 2 children lost tolerance due to inconsistent introduction; 1 temporarily withdrew due to parental concerns, but still built tolerance.

No anaphylaxis occurred during the first oral food challenge. Antihistamines were used in 10 children for minor reactions.

“Based on this case series, we suggest that regular monitoring of these children is essential to avoid prolonging the break period between the following steps of the food ladder and to monitor the regular daily introduction of tolerated forms of milk/egg,” investigators wrote.`

References

1. Wiszniewska D, Stróżyk A, Horvath A. Safety and effectiveness of milk and egg ladders in children with IgE-mediated food allergy-A case series. J Pediatr Gastroenterol Nutr. Published online May 22, 2025. doi:10.1002/jpn3.70088.

2. Cronin C, Ramesh Y, De Pieri C, Velasco R, Trujillo J. 'Early Introduction' of Cow's Milk for Children with IgE-Mediated Cow's Milk Protein Allergy: A Review of Current and Emerging Approaches for CMPA Management. Nutrients. 2023;15(6):1397. Published 2023 Mar 14. doi:10.3390/nu15061397.