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.