Severe Anaphylactic Reactions to Home Doses of Oral Immunotherapy for Food Allergy

The study purpose was to assess the rate, risk factors, and triggers for reactions to home doses of oral immunotherapy (OIT) that were treated with epinephrine.

All patients who initiated OIT at the authors’ medical center from April 2010 to January 2022 and achieved either partial or full desensitization or treatment failure by August 2022 were included. Patients over 3.5 years of age with IgE-mediated food allergy and with stable asthma for at least 3 weeks prior were offered OIT.

The OIT protocol started with clinic visits to determine the highest tolerated dose followed by subsequent up-dosing visits, after which the dose was consumed daily at home until the next up-dose. Patients received instructions about dosing, including when to premedicate, lower or skip doses, and how to manage allergic reactions. Families reported daily on their dosing and reactions. The team determined which reactions were home-epinephrine-treated reactions (HETR) and which were high grade HETR (HG-HETR), defined as reactions involving respiratory (oxygen saturation under 94%), cardiovascular (hypotension), or central nervous system impairment (loss of consciousness).

There were a total of 1637 OIT treatment courses completed to milk (880), peanut (346), tree nuts (221), sesame (115), and egg (75). Of the OIT treatments, 390 were complicated by HETR, including 268 for milk. Of the cases, 349 required a single dose of epinephrine, whereas 41 required 2 or more doses. There were 30 HG-HETRs (1.7% of all treatments), 26 to milk in patients with house dust mite allergy and asthma (26 of 30 each). Some of the associated triggers reported for the HG-HETRs included exercise, fatigue, and concurrent illness, whereas in 14 cases none were determined. Milk represented 85.2% of HG- HETR versus only 64.4% of non-HG-HETR. For milk, 2.5% of OIT treatments had HG-HETR versus 0.5% of OIT treatments for other foods. Patients that experienced HG-HETR were more likely to have a history of asthma.

HG-HETRs occur in a minority of OIT patients. The main risk factors of HG-HETRs during OIT included undergoing milk OIT, having asthma, and sensitization to house dust mite.

Although OIT is generally safe, there are risks that both the physician and patient should be aware of, including the potential for life-threatening allergic reactions. Here, about 24% of the treatment courses involved administration of epinephrine at home. Therefore, parental comfort with recognizing allergic reactions and anaphylaxis and administration of epinephrine is essential. The findings underscore the importance of shared decision making, balancing the benefits of increasing the reaction threshold against risks of reactions from treatment. This study emphasizes that milk OIT appears to carry special risks. Currently, only 1 form of OIT is Food and Drud Administration approved (for peanut using a commercial product) ,but as OIT is practiced with increasing numbers of foods, real world studies like this one help us to understand risks and benefits of this approach.