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Background: The association between pet exposure in infancy, early childhood eczema, and FLG mutations remains unclear. Methods: This was a birth cohort study performed in Tokyo, Japan. The primary outcome was current eczema based on questionnaire responses collected repeatedly from birth to 5 years of age. Generalized estimating equations and generalized linear modeling were used to evaluate the association. Results: Data from 1448 participants were used for analyses. Household dog ownership during gestation, early infancy, and 18 months of age significantly reduced the risk of current eczema. Household cat ownership also reduced the risk of current eczema, albeit without statistical significance. The combined evaluation of children from households with pets, be it cats, dogs or both, the risk of current eczema at 1–5 years of age was lower in those with household pet exposure ownership during gestation (RR = 0.59, 95 % CI 0.45–0.77) and at 6 months (RR = 0.49, 95 % CI 0.36–0.68). , Reduced risks of eczema were also observed at 2–5 (RR = 0.52, 95 % CI 0.37–0.73) and 3–5 years of age (RR = 0.50 95 % CI 0.35–0.74) when the respective household pet ownership were evaluated at 18 months and 3 years of age. These protective associations of reduced risk of eczema were only observed in children without FLG mutations. Conclusions: Household dog and pet (dog, cat, or both) ownership was protective against early childhood eczema in a birth cohort dataset. This protective association was observed only in children without FLG mutations, which should be confirmed in studies with larger cohorts.

Background: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. Methods: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). Results: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about “diagnosis-probable” patient cohort (n = 402) and the “diagnosis-confirmed” patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. Conclusions: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

To assess the risk of food allergies in foods processed under the Japanese food labeling system, estimating exposure to hidden allergens is necessary. We assessed exposure to egg protein in foods processed according to the Japanese food labeling system. First, we estimated the concentration distribution of egg protein by Bayesian methods using data from the literature and the measurement of food products with precautional declarations in the labeling margin. We then estimated the food-intake portion-size distribution under two scenarios: soft drink consumption as an example of single, high-intake consumption, and confections, which are frequently consumed by children, as a realistic example of low-intake consumption. Finally, we estimated the distribution of unexpected intake of egg proteins in the form of single consumption. The mean exposure to egg protein under the high-intake scenario was estimated to be 0.0164 mg for 1–15-year-olds, 0.0171 mg for 4–15-year-olds, 0.0181 mg for 7–15-year-olds, and ≥0.0188 mg for 16-year-olds. The mean exposure to egg protein under the low-intake scenario was estimated to be 0.0018 mg for 1–15-year-olds, 0.0019 mg for 4–15-year-olds, 0.0020 mg for 7–15-year-olds, and ≥0.0022 mg for 16-year-olds. Compared to the reference dose of 2.0 mg proposed by the Joint the Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee, the risk of onset of food allergies due to egg protein contamination from foods without egg labeling is considered to be extremely low under the current Japanese food labeling system.

Background: The effectiveness of slow low-dose oral immunotherapy (SLOIT) for cow's milk (CM) allergy has been reported. Most OIT studies have discussed the target populations over 4 years old. Furthermore, no predicting modeling is reported for CM allergy remission by CM-SLOIT under 4 years of age. Objective: We sought to develop a predictive model for CM allergy remission by SLOIT after 3 years in young children who started CM-SLOIT under 4 years of age. Methods: We included young children with cow's milk allergy or cow's milk sensitization (development modeling set with 120 children and validation modeling set with 71 children). We did logistic regression analysis to develop the models. We calculated the area under the receiver operating curves (ROC-AUCs) to evaluate the predictive modeling performance. Results: The model (CM-sIgE before SLOIT + age at beginning SLOIT + serum TARC before starting SLOIT + CM-sIgE titer one year after OIT) showed good discrimination with the ROC-AUC of 0.83 (95% CI:0.76–0.91) on internal validation. Applying the model to the validation set gave good discrimination (ROC-AUC = 0.89, 95% CI:0.80–0.97) and a reasonable calibration (intraclass correlation coefficient = 0.88, 95% CI:0.62–0.97). Conclusion: We developed and validated predictive modeling for determining the remission rate of CM allergy at 3 years after SLOIT under 4 years of age in children with CM allergy. This predictive model is highly accurate and can support CM allergy management. (226 words)

Background: Eczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns. Methods: This birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC. Results: Persistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome. Conclusions: Early-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.

This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. “Infant and preschool asthma” is diagnosed when young children (

Background: Allergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed. Objective: We sought to detect genetic variants associated with differences in immune responsiveness against allergen components. Methods: The participants of the present study were recruited from the Tokyo Children’s Health, Illness, and Development study, and allergen component–specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16). Results: We performed GWAS on 564 participants of the Tokyo Children’s Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10−8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10−8). Conclusions: Our data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.

Reports of food protein–induced enterocolitis syndrome (FPIES) in Japan have been increasing. However, the disease itself and the treatment options are poorly understood by both patients and medical professionals. The objective of this study is to develop an action plan for acute FPIES in Japan. We prepared a single–sheet action plan that describes the management of acute FPIES episodes for caregivers on one side and medical professionals on the reverse side. To evaluate the content of the action plan, we distributed a questionnaire to caregivers of patients with FPIES and to physicians who would encounter patients with FPIES. Changes to the FPIES action plan were made based on the feedback from the participants. The Delphi method was utilized to finalize the action plan. The participants of the initial survey found the action plan to be useful but the process for determining severity to be impractical. After discussion, the authors made appropriate improvements. By the Delphi method, consensus was reached on the revised FPIES action plan. In conclusion, this Japanese FPIES action plan was created by physicians from multiple subspecialties and caregivers of patients with FPIES. The action plan may improve the management of acute FPIES reactions in the Japanese community.