Food desensitization: current knowledge and future directions

Foods are reported to be primary causes for anaphylaxis⁽¹⁾ and a recent study in Montreal suggests that almost 85% of anaphylaxis cases in children are triggered by food with peanut and/or tree-nut being the major culprit⁽²⁾. At present, the only treatment for food allergy is strict avoidance of the food, while the principal treatment for an allergic reaction is prompt administration of intramuscular epinephrine (found in Epipen® and Allerject™) ⁽³⁾.

While peanut and tree nut allergy account for the majority of anaphylaxis cases, cow’s milk allergy (CMA) is the most common food allergy in children. CMA is associated with severe and frequent allergic reactions, anaphylaxis, and potential nutritional deficiencies. Due to the common use of cow’s milk in Western diets, it is almost impossible to avoid ⁽⁴⁾ and hence, new treatment strategies apart from avoidance have been sought for individuals presenting with food allergy in general and CMA in particular.

Immunotherapy has been utilized for inhalant allergies, such as to grass tree or ragweed hay fever, for over a century. Allergen Immunotherapy is based on injection of increasing amounts of a specific allergen over a prolonged period. However, attempts at food based injected-immunotherapy were associated with severe adverse effects ⁽⁵⁾. Instead of injected immunotherapy, recent studies have attempted oral administration of small, increasing amounts of the food over a period of weeks to allow patients to be able to ingest the food, a process called oral immunotherapy (OIT). Recent studies suggest that almost 80% of children can be desensitized and protected from accidental reactions through oral immunotherapy (OIT) ⁽⁶⁾⁽⁷⁾. OIT has a marked effect on immunological and clinical markers and allows for several fold increases in the threshold of food required to trigger an allergic reaction. However, while the clinical benefits of OIT inducing desensitization are promising, it is crucial to determine the safest protocols. Studies suggest that among patients undergoing OIT up to one quarter will require epinephrine - epinephrine treated reactions (ETRs). Although ETRs were a major reason for discontinuation of therapy, 75% of patients who experienced an ETR went on to reach their target dose. Furthermore, eosinophilic esophagitis may develop in 2-5% of cases⁽⁸⁾.

There are currently no guidelines describing the perfect candidate for desensitization or the safest and most effective dosing schedule⁽⁹⁾. Several initiatives exploring the effective immunotherapy for food allergies have been advanced. The ultimate goal of food allergy immunotherapy is cure, resulting in children having no symptoms after ingestion of the food even after prolonged periods of avoidance. However, it is not clear if the current food immunotherapy projects can achieve tolerance or would have to continue daily dosing to be safe⁽¹⁰⁾. A study on peanut OIT in children 1-3 years revealed that only 20% attained true tolerance following peanut OIT⁽¹¹⁾.

In a study on milk immunotherapy, 66 patients (62%) in a group treated with immunotherapy were able to tolerate a full serving of milk (about 200 mL) compared to seven (8%) of the untreated control group. In addition, 27 (25%) in the treated group could drink a smaller serving of milk (10 to 184 mL) while none could in the control group. Side effects were common, although most were local and mild⁽¹²⁾. Significantly increased thresholds to food-induced allergic reactions after oral immunotherapy were described also for other foods including egg and peanut ^(13)(14)(15).

At this point long term adherence to maintenance doses is recommended. Findings from a longitudinal study on 50 patients who completed a milk OIT escalation protocol, reaching a maintenance dose of 200 ml of milk revealed that only 56% of participants adhered to the maintenance protocol. Importantly, adherent patients experienced a lower incidence of allergic reactions, including life-threatening anaphylaxis, healthcare/ER visits, and epinephrine/antihistamine use ⁽¹⁶⁾.

In 2013 the, Division of Allergy and Clinical Immunology in The Montreal Children’s Hospital initiated a randomized controlled trial to assess oral desensitization to cow’s milk as a treatment for CMA and in 2021 the SORT (Safety of OIT in a Randomized Trial) study was initiated in order to establish the safest OIT protocol for two foods: peanut, the most common food affecting Canadian children and milk the main food allergen associated with inadvertent reactions. Numerous other studies are currently conducted to establish the safest while still effective protocols and to render OIT accessible to all Canadians with food allergies.

References

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16. Mulé P, Zhang X, Prosty C, Beaudette L, Cohen CG, Chan E, et al. Long-Term Adherence and Risk of Allergic Reactions in Patients Who Attained Milk Oral Immunotherapy Maintenance. J Allergy Clin Immunol Pract. 2024 Jun 27:S2213-2198(24)00668-8. Online ahead of print.

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Moshe Ben-Shoshan^a,b and Bruce Mazer^a

1. Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Center, Montréal, Québec, Canada
2. Division of Clinical Epidemiology, Department of Medicine, McGill University Health Center

updated 10/2024