DISCUSSION
This study, led by pediatric allergists, tracked Japanese children with immediate-type food allergies for AAR. While the annualization rate was slightly lower than that reported before, half of the children who had experienced AAR showed moderate to severe allergic reactions. Low-dose reactivity was identified as a risk factor for AAR.
Previous reports in the U.S., UK, and Australia showed an annual rate of 0.5–0.7 for AAR 11,12. In our study, the annualized rate of AAR was 0.130, which was lower than that in previous studies,11,12 and this could be attributed to three factors. First, in labeling systems, allergenic ingredients must be shown on packaged foods; however, the form of allergen lists differs in each country.19 For 15 years, food allergen labeling regulations have been enforced and periodically revised in Japan.19 Moreover, polymerase chain reaction methods have been implemented to detect allergens in Japanese products.20 Therefore, the system for allergen labeling in Japan may be relatively strict compared to that in other countries. Second, education for caregivers is important for the prevention of AAR.11,21,22 Similarly, at Sagamihara National Hospital, most guardians and children were provided instructions about the labeling and prevention of AARs by pediatricians before the study period. Third, the coronavirus disease (COVID-19) pandemic occurred during the study period. A systematic review has reported that restaurants are the most common locations for AARs.23 In a survey of allergic reactions among school-aged children, 23% of AARs developed in schools and 12% in friends’ homes.24 In our study, 59% of AARs developed at home, 13% at restaurants, and 7% at schools or nursery schools. Therefore, behavioral changes associated with the COVID-19 pandemic may have affected our study results.
In our study, half of the AAR had moderate to severe reactions. Among the eight patients who were not administered intramuscular adrenaline for anaphylaxis in AAR, five were previously prescribed auto-adrenaline injections but could not use them by themselves. Previous research indicates a similar gap in adrenaline use;11therefore, regular guidance is required for anaphylaxis caused by AAR.
This study showed that low-dose reactivity in all cohorts, HE or CM allergy, a single food allergy in HE allergy, and high sIgE level in milk in CM allergy were significant risk factors for AAR. Additionally, the number of patients who experienced AAR was significantly higher in the group with low-dose reactivity than in the group with low-dose tolerance for HE, CM, and peanut allergies. For CM allergies, a high level of sIgE could be a predictor of the development of AAR, similar to the findings of a previous study.13 In HE allergy, a single allergen was the risk factor, and the finding differed from a previous report.25 In this study, the median age at inclusion was 4.7 years. In general, it has been suggested that half of the HE allergies at this age may have acquired tolerance.26 At Sagamihara National Hospital, children with persistent allergies were referred from another hospital and included in this study; a larger cohort in a multicenter study is required. To the best of our knowledge, this is the first study to demonstrate low-dose reactivity as a risk factor in all cohorts. In school children, low-dose reactivity is one of the factors representing persistent HE or peanut allergy.27,28 Additionally, children with low-dose reactivity may have an extended period during which they are at risk of experiencing AAR compared with those with low-dose tolerance. Therefore, children with low-dose reactivity are likely to experience AAR, and evaluation of low-dose reactivity would be useful for managing food allergies. Regarding the management of children with low-dose reactivity, low-dose OITs prevented the development of AAR in wheat or peanut allergy owing to the elevated threshold to a level that allows the ingestion of low doses.29, 30Therefore, low-dose OIT may prevent AAR in the daily lives of patients with low-dose reactivity.
This study has several limitations. First, it was conducted at a single national allergy center, possibly including severe food allergies. Second, food allergy diagnosis and OFC were not performed at the study’s outset, potentially affecting diagnostic consistency and treatment. However, only children with thresholds determined within 2 years were included. Third, the study relied on patient/guardian-reported questionnaires, yet data were collected within 2-4 months, minimizing recall bias.
In conclusion, among the immediate types of HE, CM, wheat, and peanut allergies, half of the children who had experienced AAR showed moderate to severe reactions, although the annualized rate of AAR was relatively low. Children with low-dose reactivity would require careful risk management to prevent AAR.