patient care perspectives

Appropriate Ages for Oral Immunotherapy: Do They Vary by Food?

by Aikaterini Anagnostou, MD, PhD

Overview

Natural history data suggest that some food allergies, such as allergies to cow’s milk, eggs, or wheat, are more likely to be outgrown, compared with allergies to other foods such as peanuts, tree nuts, fish, and shellfish. However, outgrowing a food allergy cannot be predicted with certainty, and, immunologically, there may be a window of opportunity with oral immunotherapy (OIT) that occurs early in life.

Expert Commentary

Aikaterini Anagnostou, MD, PhD

Professor of Pediatrics
Director, Food Immunotherapy Program
Director, Food Challenge Program
Co-Director, Food Allergy Program
Lead, Adolescent Transition for Allergy
Texas Children’s Hospital
Baylor College of Medicine
Houston, TX

“Milk, egg, and wheat allergies resolve naturally in most cases, whereas only approximately 20% of peanut- and 10% of tree nut–allergic children outgrow their food allergy. The challenge is that we cannot yet identify with absolute certainty the children who will or will not outgrow their allergy.”

Aikaterini Anagnostou, MD, PhD

Age is certainly a factor when considering the use of OIT. Milk, egg, and wheat allergies resolve naturally in most cases, whereas only approximately 20% of peanut- and 10% of tree nut–allergic children outgrow their food allergy. The challenge is that we cannot yet identify with absolute certainty the children who will or will not outgrow their allergy.

We do have some guidance on patient selection and predicting the likelihood of a natural resolution of a food allergy, but it is not 100% conclusive. For example, children have a good chance of outgrowing a milk allergy if they have no other atopic comorbidities, their initial reaction involved only the skin or mucosa, their immunoglobulin E (IgE) levels and skin test results are low and decline over time, and they can tolerate the consumption of baked milk. Although, again, we still cannot say with absolute certainty that they will outgrow their allergy, they certainly have a good chance of doing so.

Conversely, a completely different profile and one that suggests a lower likelihood of outgrowing the allergy is that of children who have anaphylaxis after their initial exposure to a small amount of cow’s milk; they may have developed eczema and may already have symptoms of allergic rhinitis or asthma. When challenged with the baked form of milk, these patients have severe reactions, and their IgE levels and skin test results are very elevated from the beginning and keep rising over the next few years.

Of course, many patients do not present in such a straightforward way, leaving the allergist without a clear idea of who and when to treat. It also remains unclear why one allergen is more likely to resolve naturally than another, but there are some indications as to why early OIT is more effective in younger children. The IgE response and T-cell receptors are weaker in infants, so perhaps without a fully formed immune response there is a window of opportunity for an intervention that may change the natural course of the disease.

For the very young milk-allergic patient, one may not readily consider OIT because an allergy to cow’s milk is likely to resolve on its own. But, for the older patient who has not outgrown the milk allergy and who is not able to tolerate milk even in baked form, natural resolution is less likely and the allergy becomes a substantial lifelong burden.

Clinicians may consider using OIT in patients at an early age, when the immune system is more malleable. There is some evidence to suggest that the immune system in infants and toddlers is potentially more amenable to OIT compared with older children. The chances for desensitization and for remission or sustained unresponsiveness may be improved. Vickery and colleagues studied peanut OIT in 40 infants and toddlers and reported a nearly 80% rate of sustained unresponsiveness. Five years later, a significant number of patients were still eating peanut products regularly. While these data are limited, they support the use of OIT in the younger age group.

References

Anvari S, Anagnostou K. The nuts and bolts of food immunotherapy: the future of food allergy. Children (Basel). 2018;5(4):47. doi:10.3390/children5040047

Children’s Hospital of Philadelphia. Oral immunotherapy 101: learning module. Accessed November 9, 2021. https://www.chop.edu/centers-programs/oral-immunotherapy-program/oral-immunotherapy-101-learning-module

Foong R-X, Santos AF. Biomarkers of diagnosis and resolution of food allergy. Pediatr Allergy Immunol. 2021;32(2):223-233. doi:10.1111/pai.13389

Mori F, Giovannini M, Barni S, et al. Oral immunotherapy for food-allergic children: a pro-con debate. Frontiers Immunol. 2021;12:636612. doi:10.3389/fimmu.2021.636612

Soller L, Abrams EM, Carr S, et al. First real-world safety analysis of preschool peanut oral immunotherapy. J Allergy Clin Immunol Pract. 2019;7(8):2759-2767.e5. doi:10.1016/j.jaip.2019.04.010

Vickery BP, Berglund JP, Burk CM, et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol. 2017;139(1):173-181.e8. doi:10.1016/j.jaci.2016.05.027

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