Oropharyngeal symptoms without systemic reactions as a risk factor for food allergen intolerance: a longitudinal pediatric study

BACKGROUND: The determinants of tolerance to food allergens are not fully understood. We aimed to elucidate the longitudinal association between oropharyngeal symptoms without systemic reactions (OSw/oS) and tolerance to food allergens. METHODS: We included all patients diagnosed with single food allergy to egg (n = 121), milk (n = 55), and wheat (n = 41) using the oral food challenge test (OFC) from 2014 to 2017. These patients received oral immunotherapy at home and/or in the hospital after diagnosis by OFC. We compared the incidence proportion of tolerance within 2 years by OSw/oS and other variables for 217 patients with food allergy. We defined OSw/oS as isolated symptoms of oropharyngeal discomfort that occurred after ingestion of a safe dose of the allergenic food determined by the OFC in the first 6 months. RESULTS: Of the 217 patients (median age 37.5 months, male 64.5%), 53 developed OSw/oS (24.4%), and 151 (egg, 85 milk, 36 and wheat, 30) attained tolerance in 2 years. Patients without OSw/oS showed a significantly higher incidence of tolerance than those with the symptoms (crude hazard ratio [HR] 5.62, 95% confidence interval [CI] 3.58–8.82, p < 0.001). The association was consistently significant in the multivariable model (adjusted HR 9.50, 95% CI 5.25–17.20, p < 0.001) independent of other risk factors for intolerance, such as concomitant bronchial asthma (adjusted HR 3.33), history of anaphylaxis (adjusted HR 2.16), milk allergy (adjusted HR 2.02), and allergic symptoms with low dose OFC (adjusted HR 1.52). CONCLUSION: Our results suggest that OSw/oS may be a risk factor for intolerance to food allergens. To reveal a high risk of food allergen intolerance may help patients and their families as well as healthcare professionals prepare for the challenge of continuing oral immunotherapy.