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Allergic conjunctivitis, allergy, atopic dermatitis, birth cohort study, allergic rhinitis, food allergy, meconium-stained amniotic fluid Keywords: allergic conjunctivitis; allergic rhinitis; allergy; atopic dermatitis; birth cohort study; food allergy; meconium-stained amniotic fluid EN allergic conjunctivitis allergic rhinitis allergy atopic dermatitis birth cohort study food allergy meconium-stained amniotic fluid 1 5 5 05/30/23 20230501 NES 230501 PEER REVIEW The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/pai.13956. Data on MSAF at childbirth were retrieved from medical record transcripts, by answering yes or no to the question "Was there MSAF?". [Extracted from the article]

Background: Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. Methods: Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18‐month‐old infants and the prevalence of allergic diseases when they were aged 3 years. Results: Data for 74,349 children were analyzed. Most 18‐month‐old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05–1.34; sometimes: aOR 1.72, 95% CI 1.46–2.03; seldom: aOR 1.99, 95% CI 1.58–2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. Conclusions: Frequent soap use when bathing 18‐month‐old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well‐designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Currently, the association between the duration of neonatal phototherapy and the risk of allergic disorders has not been reported. This observational cohort study aimed to examine the association between allergic disorders, including food allergies, that are present before 3 years of age and the duration of phototherapy using the nationwide birth cohort data. Methods: The Japan Environment and Children's Study was a nationwide birth cohort study. Data of 77,064 infants aged 1 year, 1.5 years, 2 years, and 3 years were analyzed. We divided the participants into three groups: no phototherapy, short phototherapy (1–24 h), and long phototherapy (>24 h) and evaluated the cumulative incidence of allergic disorders before 3 years of age, including asthma, atopic dermatitis, and food allergies. Logistic regression analysis was performed to assess the impact of phototherapy duration on the cumulative incidence of allergic disorders. Results: After adjustment for potential risk factors, long phototherapy was found to be positively associated with food allergies at age 2 years (OR: 1.16; 95% CI: 1.01–1.33) and all allergic disorders at age 3 years (OR: 1.12; 95% CI: 1.01–1.24), including food allergies (OR 1.18; 95% CI: 1.04–1.35). Conclusion: A long duration of neonatal phototherapy was positively associated with the risk of allergic disorders, especially food allergies. [ABSTRACT FROM AUTHOR]

Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives: To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study -demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods: The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged =12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results: Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion: Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods. Infants 3–4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837). A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116–0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant. Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached. [Display omitted] [ABSTRACT FROM AUTHOR]

The number of patients with atopic dermatitis is on the rise worldwide, and Japan is no exception. According to recent estimates of the percentage of patients with atopic dermatitis in Japan by age, the majority of patients are between 20 and 44 years old. Because the peak age of onset of atopic dermatitis is during infancy, many patients may experience prolonged symptoms from infancy to adulthood. A prolonged clinical course also increases the burden of atopic dermatitis on affected patients. Decreased productivity due to work disruptions, reduced daily activity, higher direct medical costs, fatigue, and daytime sleepiness due to sleep disturbances are typical burdens on patients with atopic dermatitis. In order to reduce these burdens, it is necessary to shorten its clinical course and achieve long-term control without relying on medications, possibly by using avoidance or coping measures of aggravating factors. Typical aggravating factors of atopic dermatitis include irritant dermatitis, food allergy in children, sweating, and psychological stress in adults. Food allergy places a heavy burden on the quality of life of affected patients and their families. The effectiveness of educational interventions for sweating and psychological stress is unclear. We must also evaluate the economic burden and cost-effectiveness of interventions on the patient as aggravating factors to be addressed. [ABSTRACT FROM AUTHOR]

Skin inflammation leads to altered cytokine/chemokine production and causes systemic inflammation. The systemic mechanism of atopic dermatitis (AD) is recognized to affect systemic metabolism. This study aimed to examine the relationship between early-onset persistent eczema and body weight, height, and body mass index (BMI), in addition to food allergy in a birth cohort among infants. This study design was a nationwide, multicenter, prospective birth cohort study—the Japan Environment and Children's Study (JECS). Generalized linear models were fitted for z scores of weight, height, BMI, and food allergy to evaluate the relationship between eczema and these outcomes for infants at age1, 2, and 3 years. Persistent eczema was negatively associated with height at the age of 2 years (estimated coefficient, −0.127; 95% confidence interval [CI], −0.16 to −0.095) and 3 years (−0.177; 95% CI, −0.214 to −0.139). The same tendency was also observed with weight and BMI. Early disease onset at younger than 1 year and persistent eczema had the strongest association with development of food allergy at age 3 years (OR, 11.794; 95% CI, 10.721–12.975). One phenotype of eczema with early-onset and persistent disease creates a risk of both physical growth impairment and development of food allergy. Infants who present with the early-onset and persistent type of eczema should be carefully evaluated daily for impaired physical growth and development of food allergy. [ABSTRACT FROM AUTHOR]

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children's Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year. [ABSTRACT FROM AUTHOR]

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible. [ABSTRACT FROM AUTHOR]

The association between early daycare attendance and risk of allergic diseases remains inconclusive. Therefore, we examined the association among Japanese children on a long-term basis using a nationwide longitudinal survey data. We estimated the association between daycare attendance at age 6 or 18 months and allergy development using information on outpatient visits for atopic dermatitis (AD), food allergy (FA), and asthma and admission for asthma up to 12 years of age as a proxy for developing these diseases, with multilevel logistic regression. Early daycare attendance was associated with increased odds of AD at ages 2.5–3.5 years: the adjusted odds ratio (OR) was 1.34 [95% CI: 1.21, 1.47]. The association with FA was equivocal. The odds of asthma was increased before age 3.5 years and afterwards decreased: the adjusted ORs were 1.60 [1.44, 1.77] for ages 1.5–2.5 years and 0.77 [0.69, 0.87] for ages 5.5–7 years. The effect of early daycare attendance depends on the type of allergies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Prenatal selenium exposure was inversely associated with allergic disease risks. • The inverse associations were more evident for lower mercury exposure. • Selenium-rich foods but not predatory fish are recommended for pregnant women. • Selenium exposure may be beneficial for allergic disease risk reduction. Prenatal exposure to metallic elements may adversely affect early childhood health. However, more evidence is needed as population-based cohort studies are currently limited. We aimed to examine the associations between prenatal metallic (mercury, selenium, and manganese) exposure and the risk of allergic diseases in early childhood until three years of age. The data from 94,794 mother-infant pairs, who participated in the Japan Environment and Children's study, were used in this study. Prenatal metallic element exposure was measured in maternal blood collected during mid-pregnancy. The incidence of atopic dermatitis, food allergies, asthma, and allergic rhinitis during the first three years of life was prospectively investigated using self-reports of physician-diagnosed allergies. A multivariable modified Poisson regression model was used to estimate the cumulative incidence ratio and their 95% confidence intervals of allergic diseases associated with prenatal exposure to mercury, selenium, and manganese. We further evaluated the interaction between mercury and selenium exposures in this association. We confirmed 26,238 cases of childhood allergic diseases: atopic dermatitis, food allergies, asthma, and allergic rhinitis in 9,715 (10.3%), 10,897 (11.5%), and 9,857 (10.4%), 4,630 (4.9%), respectively. No association was found between prenatal mercury or manganese exposure and the risk of allergic diseases. Prenatal selenium exposure was inversely associated with atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases, but not with asthma. These inverse associations were more pronounced for lower mercury exposures than for higher exposures. Our findings suggest that prenatal exposure to selenium may be beneficial for reducing the risk of atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases in early childhood, especially with lower prenatal mercury exposure. [ABSTRACT FROM AUTHOR]

Dear Editor, Fish allergy (FA) is the second most frequent type of food allergy in Japan.[1] Fish allergens listed in the database of the World Health Organization include parvalbumin, which is known to be the major allergen, -enolase, aldolase A, vitellogenin and tropomyosin.[2] Patients with atopic dermatitis (AD) have an increased risk for sensitization to allergens because of their increased skin barrier permeability.[3] Here, we enrolled six patients with FA, who had also been diagnosed with AD according to the diagnostic criteria of the Japanese guidelines.[4] A table summarizing the clinical details of the patients and controls is available on request from the authors. All the patients showed immediate-type responses, such as urticaria or anaphylaxis, upon eating fish and had positive results on skin prick tests and/or serum IgE reactivity with CAP for fish allergens. The expected allergen recognized by the patient's IgE but not by the control IgE was a protein of approximately 230 kDa at a I pI i of 4-5-6-0 (Fig. b, c). [Extracted from the article]

The manifestation of atopic dermatitis (AD) is initially nonatopic eczema in early infancy; the manifestations subsequently change in age-specific stages. Since allergen-specific T-helper 2 cells appear in the fetus primarily after the third trimester of pregnancy and rapidly mature during the first 6 months of life, different timings of tobacco smoke exposure may have different effects on AD. In this study, we investigated whether the timing of fetal or/and infantile tobacco smoke exposure affects the cumulative incidence of atopic eczema/dermatitis syndrome (AEDS) in infants in Japan. This cross-sectional study enrolled 1,177 parent-infant pairs, in which the infants were >6 months old. Parental allergic history, number of older siblings, physician-diagnosed AEDS and food allergy (FA), and the perinatal fetal and/or infantile tobacco smoke exposure timing after 28 weeks gestation and during the first 6 months of life were assessed using self-completed questionnaires. Fetal tobacco smoke exposure after 28 weeks gestation was significantly associated with higher cumulative incidence of AEDS in exposed infants than in unexposed infants: AEDS in all infants, 41.4% versus 34.0% (Chi-squared, P = 0.020; adjusted odds ratio, 5.21; 95% confidence interval, 1.08-25.15); AEDS in those without parental allergic history, 38.0% versus 26.6% (Chi-squared, P = 0.024). Postnatal infantile tobacco smoke exposure timing was not significantly associated with cumulative incidence of AEDS. No significant associations were observed between any tobacco smoke exposure timings and the cumulative incidence of FA. Fetal tobacco smoke exposure during the third trimester of pregnancy was positively associated with AEDS in infancy and might induce epigenetic changes in the fetal allergen-specific immune responses. [ABSTRACT FROM AUTHOR]

Population-based cross-sectional study was performed to estimate the prevalence of chemical intolerance and to examine the characteristics of the sample. A Web-based survey was conducted that included 7,245 adults in Japan. The criteria for chemical intolerance proposed by Skovbjerg yielded a prevalence of 7.5% that was approximately consistent with that reported from a Danish population-based survey. Female gender, older age, and renovation in the house during the past 7 years were positively associated with chemical intolerance. Improvements in the condition were observed with daily ventilation habits. Medical history of atopic dermatitis, allergic rhinitis, food allergy, multiple chemical sensitivity, and depression were associated with chemical intolerance. Fatigue, depressed mood, and somatic symptoms were also positively correlated with chemical intolerance. Better elucidation of the causes, comorbidities, concomitants, and consequences of chemical intolerance has the potential to provide effective solutions for its prevention and treatment. [ABSTRACT FROM PUBLISHER]

Food allergy is defined as "a phenomenon in which adverse reactions (symptoms in skin, mucosal, digestive, respiratory systems, and anaphylactic reactions) are caused in living body through immunological mechanisms after intake of causative food." Various symptoms of food allergy occur in many organs. Food allergy falls into four general clinical types; 1) neonatal and infantile gastrointestinal allergy, 2) infantile atopic dermatitis associated with food allergy, 3) immediate symptoms (urticaria, anaphylaxis, etc.), and 4) food-dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate-type food allergy). Therapy for food allergy includes treatments of and prophylactic measures against hypersensitivity like anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be conducted only if they are inevitable because they places a burden on patients. For this purpose, it is highly important that causative foods are accurately identified. Many means to determine the causative foods are available, including history taking, skin prick test, antigen specific IgE antibodies in blood, basophil histamine release test, elimination diet test, oral food challenge test, etc. Of these, the oral food challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions such as anaphylaxis. [ABSTRACT FROM AUTHOR]

Abstract Background: Allergens that cause food allergy vary considerably according to race, environment, dietary habits and age. However, data on the actual situation of food allergy in young adult students are limited in Japan. The aim of the present study was to investigate the actual situation of food allergy in young adults. Methods: Food allergy was examined, along with the presence or absence of allergic rhinitis, atopic dermatitis and bronchial asthma complicating food allergy, in 2053 Japanese university students. Results: Food allergy was noted in 5.2% of subjects, with a higher prevalence in female students. In terms of the causative allergen, the rank order of incidence was egg, buckwheat, shrimp, crab, mackerel, milk, yam, beef fat, shellfish and other foods. In comparison with Western countries, the incidence of allergy to buckwheat and seafood tended to be higher. Among students with a food allergy, the proportion of those with allergic rhinitis, atopic dermatitis and bronchial asthma was 45.8, 29.0 and 12.1%, respectively, showing higher prevalences than in students without any food allergy. Conclusion: In the future, the number of young adults with food allergy complicated by other allergic diseases will increase and measures against this issue seem to be necessary. [ABSTRACT FROM AUTHOR]