patient care perspectives

Challenges and Opportunities in the Management of Pediatric Food Allergy

by David M. Fleischer, MD

Overview

Researchers are pursuing additional diagnostic, predictive, and prognostic tools for use in the approach to food allergy. Additionally, clinical trials of biologic therapies are currently underway to try to improve outcomes in populations with multiple food allergies.

Expert Commentary

David M. Fleischer, MD

Section Head, Allergy and Immunology
Professor of Pediatrics
Director, Allergy and Immunology Center
Children’s Hospital Colorado
University of Colorado Denver School of Medicine
Aurora, CO

“No one wants their child to have food allergies, but I tell families to try not to be discouraged, that the allergies may not be there for the rest of the child’s life, and that we are at a good point in history right now because there is a lot of research being done.”

David M. Fleischer, MD

The gold standard of whether or not someone is allergic to a food is whether they can eat that food without reaction, which is the basis for the oral food challenge (OFC). During an OFC, the patient eats the food in gradually increasing amounts, under the supervision of an allergist, and is observed for any possible allergic reaction. We are looking for alternative ways to diagnose and manage food allergy that may not involve OFCs; however, it is unclear at this point if we will have tools that are as accurate as the OFC, as this is currently considered to be the best test to determine whether someone is allergic, or not allergic, to a particular food.

Performing OFCs requires significant resources in terms of staff and space. At our institution, we are very fortunate to have the resources to do many OFCs, and we perform several thousand OFCs each year. Other academic centers or private practice settings may differ in their ability to perform OFCs, however, and some may prefer not to perform OFCs if they lack the resources to do them safely. You need to have the physical space, which includes a patient room that is dedicated to monitoring those who are undergoing OFC, and you need to have a dedicated clinician and nurse to watch these patients closely for allergic reactions and to treat them promptly and appropriately when they occur.

Some of the opportunities in food allergy relate to our ability to be more precise with diagnosis. Component-resolved diagnostics have allowed us to take a closer look at the individual allergen proteins. There are several peanut-component proteins (eg, Ara h 1, 2, and 3), and Ara h 2 is one of the most important component allergens within patients with peanut allergy. It has recently been determined that Ara h 2–specific immunoglobulin E (IgE) performs well as a tool for peanut allergy diagnosis, more so than skin testing or whole peanut IgE levels. There are also egg- and cow’s milk–component proteins, and components are being investigated in tree nuts and other allergens as well, so there is more to come in this area.

There is also interesting work related to epitopes, or regions of the allergenic protein that are recognized by the antibodies, owing to the protein’s 3-dimensional structure and features such as folding patterns. Not all antibodies against an allergen are clinically relevant, as evidenced by the high false-positive rate observed in IgE testing in patients who have more severe eczema, for example, and positive IgE tests to foods that they are safely eating without reaction. There is interest in epitope mapping as part of an effort to better predict which individuals will outgrow their food allergy and which will not. With further development, epitope mapping might also be used to predict which routes of immunotherapy (eg, epicutaneous vs oral) may be best suited for a particular patient.

There are several exciting monoclonal antibodies that are currently in development that may potentially improve outcomes in patients with multiple food allergies who seek food immunotherapy. For instance, omalizumab is an anti-IgE antibody that is being studied in the phase 3 OUtMATCH trial, which is enrolling patients 1 to 56 years of age who are allergic to peanuts and at least 2 other foods that are commonly implicated in food allergies. It already has indications for allergic asthma, nasal polyps, and chronic spontaneous urticaria. We hope to learn whether omalizumab injections alone or in combination with multiallergen oral immunotherapy will help optimize outcomes in people with multiple food allergies. Hopefully, we will have a US Food and Drug Administration approval within the next year or 2. Dupilumab, another monoclonal antibody, is being studied in a phase 2 multiallergen oral immunotherapy trial for the treatment of food allergy. Patients in the study have proven allergies to 2 or 3 foods, one of which must be peanuts, and are being randomized to omalizumab plus placebo, omalizumab plus dupilumab, or placebo plus dupilumab. Dupilumab inhibits interleukin-4 and interleukin-13 signaling, and it currently has indications for severe eczema and severe asthma.

No one wants their child to have food allergies, but I tell families to try not to be discouraged, that the allergies may not be there for the rest of the child’s life, and that we are at a good point in history right now because there is a lot of research being done. This is a good time to be in research, and families can be excited about that, as I am, too, about the future possibilities.

References

Ansotegui IJ, Melioli G, Canonica GW, et al. IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper [published correction appears in World Allergy Organ J. 2021;14(7):100557]. World Allergy Organ J. 2020;13(2):100080. doi:10.1016/j.waojou.2019.100080

Bird JA, Leonard S, Groetch M, et al. Conducting an oral food challenge: an update to the 2009 Adverse Reactions to Foods Committee Work Group report. J Allergy Clin Immunol Pract. 2020;8(1):75-90.e17. doi:10.1016/j.jaip.2019.09.029

ClinicalTrials.gov. Clinical study using biologics to improve multi OIT outcomes. Updated August 31, 2021. Accessed January 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03679676

ClinicalTrials.gov. Omalizumab as monotherapy and as adjunct therapy to multi-allergen OIT in food allergic participants (OUtMATCH). Updated September 16, 2021. Accessed January 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03881696

Ehlers AM, Blankestijn MA, Knulst AC, Klinge M, Otten HG. Can alternative epitope mapping approaches increase the impact of B-cell epitopes in food allergy diagnostics? Clin Exp Allergy. 2019;49(1):17-26. doi:10.1111/cea.13291

Foong R-X, Dantzer JA, Wood RA, Santos AF. Improving diagnostic accuracy in food allergy. J Allergy Clin Immunol Pract. 2021;9(1):71-80. doi:10.1016/j.jaip.2020.09.037

Gupta RS, Warren CM, Smith BM, et al. The public health impact of parent-reported childhood food allergies in the United States [published correction appears in Pediatrics. 2019;143(3):e20183835]. Pediatrics. 2018;142(6):e20181235. doi:10.1542/peds.2018-1235

Keet C, Plesa M, Szelag D, et al. Ara h 2–specific IgE is superior to whole peanut extract–based serology or skin prick test for diagnosis of peanut allergy in infancy. J Allergy Clin Immunol. 2021;147(3):977-983.e2. doi:10.1016/j.jaci.2020.11.034

Koplin JJ, Perrett KP, Sampson HA. Diagnosing peanut allergy with fewer oral food challenges. J Allergy Clin Immunol Pract. 2019;7(2):375-380. doi:10.1016/j.jaip.2018.11.010

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