Background: Approximately 50–90% of children with immediate-type cow’s milk allergy (CMA) acquire tolerance by pre-school age. We aimed to investigate the tolerance acquisition rate of CMA in children aged 6–12 years. Methods: Children with CMA that persisted until 6 years of age were included. Tolerance acquisition was defined as either passing an oral food challenge with 200 mL of unheated cow’s milk (CM) or consuming CM of any quantity without symptoms. Persistent CMA was defined as fulfilling neither of these criteria by 12 years of age. Children undergoing oral immunotherapy were defined as having persistent CMA. Risk factors associated with persistent CMA were assessed using Cox regression analysis. Results: Of the 123 children analyzed, 60 (49%) had previous CM anaphylaxis, 82 (67%) eliminated CM from their diet, and the median CM-specific immunoglobulin E (sIgE) level was 23.3 kU A/L at 6 years of age. Twenty-five children (20%) acquired tolerance by 9 years of age, and 46 (37%) by age 12. At baseline, higher CM-sIgE levels (hazard ratio: 2.58 [95% confidence interval: 1.62–4.12], optimal cutoff level: 34.4 kU A/L), previous CM anaphylaxis (2.42 [1.24–4.69]), and complete CM elimination (5.18 [2.45–10.99]) were associated with persistent CMA. None of the children with CMA who had all three risk factors (n = 26) acquired tolerance. Conclusion: At least one-third of the children with CMA at 6 years of age acquired tolerance by 12 years of age. Children with CMA who have the risk factors are less likely to acquire tolerance.

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

Clinical cross-reactivity to quail’s egg in patients with hen’s egg allergyMasatoshi Mitomoria, Noriyuki Yanagidaa, Mari Takeib, Kinji Tadab, Makoto Nishinoa, c, Sakura Satob, 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, JapancCourse of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine, Tokyo, JapanRunning title: Clinical cross-reactivity of HE & QECorresponding author:Noriyuki Yanagida18-1, Sakuradai, Minamiku, Sagamihara, Kanagawa 252-0392, JapanTel.: +81 042 742 8311 Fax: +81 042 742 5314E-mail: [email protected]

Treatment-required accidental ingestion and risk factors among nursery children with wheat allergy

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