Factors Associated With Home Epinephrine-Treated Reactions During Peanut and Tree-Nut Oral Immunotherapy

To identify risk factors for home epinephrine-treated reactions (HETR), a marker of severe reactions during oral immunotherapy (OIT) to peanut and tree nuts.

Participants included 642 patients, aged 3.7 to 35.6 years (median age 6.8 years), with a confirmed allergy to peanut, tree nut (walnut, cashew, hazelnut), sesame, or egg who underwent 756 OIT treatments in an open-label OIT program.

Enrolled patients had immunoglobulin E sensitization to the treated food and either a history of recent (within the last year) allergic reaction or a positive oral food challenge. They were first evaluated in the clinic to confirm the diagnosis and determine the individualized single highest tolerated dose (SHTD), which did not elicit symptoms. Patients then ingested the SHTD at home daily with up-dosing in the office every 4 weeks with a goal of reaching a maintenance dose of 300 mg daily for most foods. Any severe reactions (defined by severe abdominal pain, significant shortness of breath, lethargy, or otherwise if in doubt) were recommended to be treated with epinephrine and were later assessed by questionnaire for potential triggers.

Full desensitization was achieved in 656 treatments (86.7%), partial desensitization in 64 (8.4%), and 37 (4.9%) failed to reach the maintenance dose. HETRs occurred in 83 patients (10.9%) and reactions treated with epinephrine during clinic up-dosing occurred in 107 patients (14.2%). In 34% of HETRs, no trigger could be identified beyond the OIT dose. In cases where a specific trigger was identified, physical exercise (19%) was the most common, followed by fatigue (12%) and concurrent illness (10%). Asthma exacerbations were not a trigger in any of the HETRs. Risk factors for HETR were older age (P = .04), a history of anaphylactic reactions, a reaction treated with epinephrine or in the emergency department before OIT or during in-clinic OIT induction (P < .001), and a low SHTD at OIT start (P = .001).

The main risk factor for HETRs was the severity of reaction(s) to the treated food before or during the induction of OIT. HETRs also increased with increasing patient age in early and midadolescence and lower SHTD. Some triggers identified in this study (exercise, illness, and fatigue) have been described in other studies, although no trigger was identified in one-third of HETRs.

Food OIT is a treatment pediatricians may increasingly encounter patients receiving and ensuring these patients carry an epinephrine autoinjector is important. Despite potential benefits, safety concerns exist and further understanding of triggers for reactions may improve its utility, particularly in patients where no trigger is identified.