Background: Accidental allergic reactions (AAR) in children are under-studied, especially with precise pediatrician-based exact diagnoses and follow-ups. This study aimed to assess the prevalence and risk factors for AAR in Japanese children with immediate-type food allergies. Methods: This single-center study included children with immediate-type hen’s egg (HE), cow’s milk (CM), wheat, or peanut allergy who had been followed-up regularly at a national center specialized for allergy in Japan. Low-dose reactivity was defined as allergic reactions to a low dose of ≤250, ≤102, ≤53, or ≤133 mg HE, CM, wheat, or peanut protein, respectively. From January to December 2020, pediatricians followed the AAR experience every 2–4 months. Risk factors for AAR were analyzed using multiple logistic regression. Results: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. In this cohort, the median age was 5.0 years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annual AAR rate was 0.130 in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall, HE, and CM cohorts, respectively ( p <0.001, p = 0.029 and 0.036). Conclusion: In Japanese children with immediate-type food allergies, the annualized rate of AAR was relatively low; however, half of the participants with AAR had moderate to severe symptoms. Children, especially those with low-dose reactivity, would require careful risk management of AAR.

Prognosis of infantile food protein-induced enterocolitis syndrome to wheat: A case series Makoto Nishino1,2 | Noriyuki Yanagida1,3,* | Sakura Sato1 | Ken-ichi Nagakura3,4 | Kyohei Takahashi3 |Kiyotake Ogura3| Motohiro Ebisawa11 Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan2 Department of Pediatrics, Ushiku Aiwa General Hospital, Ibaraki, Japan3 Department of Pediatrics, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan4 Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan*Corresponding author: Noriyuki YanagidaDepartment of Pediatrics, National Hospital Organization Sagamihara National Hospital,18-1, Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, JapanE-mail:[email protected] count: 1,191Number of figures: 2 Number of tables: 1

Background: Food allergy is a disease with a diverse and variable natural history, and some patients may react to two or more food antigens. This study aimed to classify and characterize the long-term prognosis of infantile-onset, immediate-type food allergies in children, focusing on three major antigens in Japan: egg, milk, and wheat. Methods: All children visited to our hospital with food allergies, including suspected cases, were prospectively registered in our medical database. From this database, infants who had immediate-type symptoms or were sensitized to above three antigens were included. Cox regression analysis and repeated-measures latent class analysis were performed to reveal risk factors and tolerance patterns for food allergies. Results: Of 2,830 patients registered in the database, we included 915 patients with immediate-type food allergy symptoms and 276 sensitized asymptomatic patients in this study. The number of patients with immediate-type symptoms to egg, milk, and wheat was 609, 443, and 235, respectively. The number of patients with multiple food allergies was 302. Ratios of acquiring tolerance to egg, milk, and wheat at the age of 6 years were 74%, 69%, and 75%, respectively. Latent class analysis revealed 10 classes of prognosis for food allergies, including five with multiple food allergies. The largest class was transient egg allergy alone (21.4%), and there were severe cases of persistent allergy to three major allergens (3.2%). Conclusions: This study demonstrated the prognosis of food-allergy classes in Japan, including multiple food allergies, with 10 classes with its own characteristics.

Threshold and safe ingestion dose among infants sensitized to hen’s eggMasatoshi Mitomori,a Noriyuki Yanagida,aMakoto Nishino,a Kyohei Takahashi,aKen-ichi Nagakura,a Kiyotake Ogura,aMari Takei,b Sakura Sato,b Motohiro EbisawabaDepartment of Pediatrics, National Hospital Organization, Sagamihara National Hospital, Kanagawa, JapanbClinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, JapanRunning title: Threshold and safe ingestion dose of egg

Previous history of immediate reactions changes predictive accuracy for pediatric peanut allergyNaoko Fusayasua, MD, Tomoyuki Asaumia, MD, Kyohei Takahashia,b, MD, Ken-ichi Nagakuraa,c , MD, PhD, Makoto Nishinoa,b, MD, Sakura Satob,d, MD, Noriyuki Yanagidaa,d, MD, Motohiro Ebisawad, MD, PhD,aDepartment of Pediatrics, National Hospital Organization Sagamihara National Hospital, Kanagawa, JapanbCourse of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine, Tokyo, JapancDepartment of Pediatrics, Jikei University School of Medicine, Tokyo, JapandDepartment of Allergy, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan