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A single-arm study was conducted with 10 children aged 2–12 years with severe cow's milk allergy (CMA) requiring complete allergen elimination. Subjects were administered kestose, a prebiotic, at 1 or 2 g/day for 12 weeks. Results of a subsequent oral food challenge (OFC) showed a statistically significant increase in the total dose of cow's milk ingestion (1.6 ml vs. 2.7 ml, p = 0.041). However, the overall evaluation of the OFC results, TS/Pro (total score of Anaphylaxis Scoring Aichi (ASCA)/cumulative dose of protein), showed no statistically significant improvement, although the values were nominally improved in seven out of 10 subjects. The 16S rDNA analysis of fecal samples collected from the subjects revealed a statistically significant increase in the proportion of Faecalibacterium spp. (3.8 % vs. 6.8%, p = 0.013), a type of intestinal bacterium that has been reported to be associated with food allergy. However, no statistically significant correlation was found between Faecalibacterium spp. abundance and the results of the OFC. [ABSTRACT FROM AUTHOR]

Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having allergen-specific IgE) to foods without exhibiting clinical reactivity. Some food groups such as shellfish, fish, tree nuts, and peanuts have very high rates of cross-reactivity. In contrast, relatively low rates are noted for grains and milk, whereas many other food families have variable rates of cross-reactivity or are not well studied. Although classical cross-reactive carbohydrate determinants are clinically not relevant, α-Gal in red meat through tick bites can lead to severe reactions. Multiple sensitizations to tree nuts complicate the diagnosis and management of patients allergic to peanut and tree nut. This review discusses cross-reactive allergens and cross-reactive carbohydrate determinants in the major food groups, and where available, describes their B-cell and T-cell epitopes. The clinical relevance of these cross-reactive B-cell and T-cell epitopes is highlighted and their possible impact on allergen-specific immunotherapy for food allergy is discussed. [ABSTRACT FROM AUTHOR]

Background: The effects of regular soy formula (SF) intake on the development of food sensitization in infancy remain unclear. This study aimed to assess the effects of regular SF intake between 1 and 2 months of age on food sensitization development by 6 months of age. Methods: Using data from a randomized controlled trial of a birth cohort from four Japanese hospitals that assessed cow's milk allergy development, we performed a retrospective cohort study of 235 infants who avoided cow's milk formula and supplemented breastfeeding with SF as required between 1 and 2 months of age. Regular SF intake was defined as SF consumption of ≥14 days per month and ≥1350 ml per month. Food sensitization was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, and/or soy. Using multivariable logistic regression models that adjusted for parental, perinatal, and environmental factors, we calculated the adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization by 6 months of age. Results: From the 235 participants, 114 (48.5%) had regular SF intake. The adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization were 0.32 (95% confidence interval: 0.16–0.62, p =.0007), 0.42 (0.20–0.88, p =.02), and 0.33 (0.14–0.81, p =.02), respectively. Conclusion: Regular SF intake between 1 and 2 months of age in infants avoiding cow's milk formula was significantly associated with a reduced risk of food sensitization in infancy. [ABSTRACT FROM AUTHOR]

Keywords: anaphylaxis; food hypersensitivity; glucocorticoid; prednisolone; steroid EN anaphylaxis food hypersensitivity glucocorticoid prednisolone steroid 537 539 3 01/31/23 20230201 NES 230201 To the Editor, Glucocorticoids (GCs) are widely used to prevent and treat anaphylaxis. Further, we conducted murine models of anaphylaxis to determine the rapid effect of GCs in preventing anaphylaxis and reducing FA symptom exacerbations using the active systemic anaphylaxis, passive cutaneous anaphylaxis, and FA models[[4]] (Methods S1). Anaphylaxis, food hypersensitivity, glucocorticoid, prednisolone, prednisolone, steroid. [Extracted from the article]

Keywords: basophils; casein; cow milk; food allergy; milk hypersensitivity; phosphopeptide EN basophils casein cow milk food allergy milk hypersensitivity phosphopeptide 1 5 5 03/29/22 20220301 NES 220301 ACKNOWLEDGMENTS We thank all the physicians, nutritionists, and nurses who performed the OFCs and data collection and Mr. Noboru Hayakawa (Clinical Laboratory technician in Aichi Children's Health and Medical Center) and Ms. Kumiko Matsuo (Cell Biology Section, BML, Inc.) for their excellent technical assistance. First, symptoms that developed after ingesting CPP-ACP containing paste or gum were possibly not induced by CPP-ACP because OFC using CPP-ACP was not performed, the time between OFC and episode was sometimes long, and I in vitro i tests were performed with CPP instead of CPP-ACP. We recruited six patients with CMA whose severity was similar to that of CPP-ACP (reacted <10 ml of CM) and who presented with casein-specific IgE titer levels above two digits and completely avoided CM for the in vitro tests (Table S1). Third, the CPP reagent used in our experiments was a mixture of trypsin-digested casein peptides, which might contain residual protein IgE epitopes, along with the CPP region in casein. [Extracted from the article]

Background: We have previously reported that more than half of the patients who achieved desensitization after wheat rush oral immunotherapy (OIT) developed exercise‐induced allergic reaction on desensitization (EIARD). However, data on EIARDs after slow OIT are lacking. Therefore, this study aimed to investigate the results of exercise provocation tests (EPTs) in patients after slow OIT for cow's milk and wheat allergies. Methods: This was a retrospective chart review of 87 EPTs in 74 patients. The EPTs were performed in patients who were desensitized to at least 6,600 mg cow's milk protein or 5,200 mg wheat protein with slow OIT and were identified to be at a high risk of EIARDs. EPTs were performed after ingestion of the maximum desensitization dose. The patients' clinical characteristics and symptoms were analyzed. Results: The EPT results were positive for cow's milk in 49% (21/43) of the patients and for wheat in 48% (15/31) of the patients. There was no significant difference in the clinical characteristics between the EIARD‐positive and EIARD‐negative groups. The specific IgE (sIgE) levels before OIT and the reduction rates of sIgE before and after OIT did not correlate with the outcomes of the EPTs. Among the EIARD‐positive patients, 13 patients (cow's milk, n = 7; wheat, n = 6) underwent a second EPT, and the EIARD disappeared in 8 patients (cow's milk, n = 4; wheat, n = 4). Conclusion: EIARDs were observed after slow OIT for cow's milk and wheat. Further research into the predictive factors of EIARDs in these patients is needed to understand its clinical manifestations. [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]

Background: There are expanding indications for oral food challenges (OFCs). Although several studies have examined the risk of OFCs, little has been reported on allergic reactions during OFCs depending on the indication. This study assessed the prevalence, severity, and treatment of allergic reactions depending on the indication for OFCs. Methods: We performed a prospective multicenter study between March 2012 and May 2013. Severity of symptoms elicited by OFCs was classified according to grading of anaphylaxis that ranges from grade 1 (most mild) to grade 5 (most severe). Results: A total of 5062 cases (median age, 3.8 years; males, 65.2%) were analyzed. Allergic reactions were elicited in 2258 (44.6%) OFCs, of which 991 (43.9%) were classified as grade 1, 736 (32.6%) were classified as grade 2, 340 (15.1%) were classified as grade 3, and 191 (8.5%) were classified as grade 4‐5. Epinephrine was administered in 7.1% (n = 160) of positive OFCs. Among the top three most common food allergens (hen's egg, cow's milk, and wheat), severity differed significantly depending on the indication for OFC, and adjusted standardized residuals indicated that severity of allergic reactions was higher for the indication to assess threshold level for oral immunotherapy. In addition, the prevalence of epinephrine use was highest for the indication to determine safe intake quantity. Conclusions: Our study suggested that prevalence, severity, and treatment of allergic reactions differ depending on the indication for OFC. Further studies are needed to determine differences in risks depending on the indication for OFC. [ABSTRACT FROM AUTHOR]

Summary: Background: Soya bean is a major food allergen in children. Component‐resolved diagnostics has improved the accuracy of diagnosing immunoglobulin E (IgE)‐mediated food allergies. Objective: We aimed to develop a novel component for the diagnosis of soya bean allergy using recombinant technology. Methods: Japanese paediatric patients with suspected soya bean allergy (n = 91) were included, and symptomatic (n = 40) and asymptomatic (n = 51) cases were divided through oral food challenge testing. Specific IgE (sIgE) antibodies to each recombinant allergen component were analysed by enzyme‐linked immunosorbent assay, and the diagnostic performances of the components were assessed by area under the receiver operating characteristic curves (AUC). Results: Among the recombinant components, sIgE antibody levels to Gly m 8 showed the highest AUC (0.706). A combination of Gly m 8 and α' subunit of Gly m 5, improved the diagnostic performance of the single components. Moreover, the N‐terminal extension region of α' subunit of Gly m 5, which has low cross‐reactivity among the vicilins, showed higher diagnostic performance (AUC 0.695) than the full‐length α' subunit of Gly m 5 (AUC 0.613). Based on these findings, we developed a fusion protein of Gly m 8 plus the extension region of α' subunit of Gly m 5; this fusion protein was very efficient for diagnosing soya bean allergy (AUC 0.801). Conclusion: A fusion protein of Gly m 8 and the extension region of α' subunit of Gly m 5 could potentially diagnose soya bean allergy in paediatric patients. Fusion proteins may be useful for producing novel allergen components with improved diagnostic value. [ABSTRACT FROM AUTHOR]

Background The appropriate usage of an adrenaline auto-injector (AAI, Epipen ® ) is a key aspect of patient and social education in the management of anaphylaxis. However, although AAIs are being prescribed increasingly frequently, there are few reports on their actual use. Methods The Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which AAIs were used. Two hundred and sixty-six cases were collected from March 2014 to March 2016. Results The cases included 240 events of immediate-type food allergies caused by cow's milk (n = 100), hen's egg (n = 42), wheat (n = 40), and peanuts (n = 11). Exercise-related events were reported in 19 cases; however, the diagnosis of food-dependent exercise-induced anaphylaxis with a specific causative food was only made in 4 cases (wheat, n = 2; fish, n = 1; squid, n = 1). The frequent reasons for the causative intake included programmed intake (n = 48), failure to check the food labeling (n = 43), and consuming an inappropriate food (n = 26). AAIs were used at schools or nurseries in 67 cases, with school or nursery staff members administering the AAI in 39 cases (58%). On arriving at the hospital, the symptom grade was improved in 71% of the cases, while grade 4 symptoms remained in 20% of the cases. No lethal cases or sequelae were reported. Conclusions AAIs were used effectively, even by school teachers. The need to visit a hospital after the use of an AAI should be emphasized because additional treatment might be required. [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]

Background Autumn and winter birth ( AWB) has been reported to be a risk factor for the development of food allergies. However, the association between seasonal factors and allergic sensitization during early infancy remains unclear. Methods We collected data from 732 patients regarding the total and specific immunoglobulin E ( tIgE, sIgE) levels in infants younger than 6 months old from November 2001 to October 2012 from the institutional clinical database system. We then analyzed the relationship between the birth month and the value of each parameter. Furthermore, we identified any correlations between the number of sensitized patients and the monthly climatological parameters. Results The number of tIgE samples obtained from AWB patients (n = 482) was 2.1 times higher than that from patients born in the spring and summer ( SSB, n = 225). The number of sIgE samples to egg white, cow's milk, and wheat, the sensitized ratio and the median sIgE titer were also all higher in AWB. The number of sensitized AWB patients to these allergens was 2.75, 3.05, and 3.97 times higher, respectively. A periodic change in the number of sensitized patients was observed annually (highest in October-November and lowest in May). Among the climatological parameters examined, the average solar radiation during the 3-month period after birth showed the strongest negative correlation with the number of sensitized patients (egg white: r = −0.976, cow's milk: r = −0.969, wheat: r = −0.975). Conclusions The amount of solar radiation immediately after birth had a strong negative correlation with allergen sensitization before 6 months of age. [ABSTRACT FROM AUTHOR]

Background This study examined the relationship between the season of birth (SoB) and other factors with the development of FA. Methods A multicenter, cross-sectional pilot study recruited 1197 patients with FA. The main study recruited 440 incident cases ( FA group) definitively diagnosed as FA at 0-1 year of age. In both studies, the frequency of autumn-winter births ( AWBs) in FA patients was compared to the regional control population. In the main study, we analyzed the differences in the SoB and other factors between patients in the FA group and those in the non- FA group (n = 332) in allergy clinics. Results The pilot study showed that the frequency of AWB (57.6%) in the FA patients was significantly higher than that of the regional control population (50.4%, OR, 1.34; p < 0.001). The main study also showed the dominance of AWB (62.7%) in the FA group in comparison with that in the regional control population (50.2%, OR, 1.70; p < 0.001). Preterm birth ( OR, 0.43; p = 0.027) and the presence of two or more elder siblings ( OR, 0.27; p = 0.012) were significantly associated with a lower frequency of FA than those of non- FA. AWB ( RR, 1.21; p = 0.020) and preterm birth ( RR, 0.55; p = 0.017) were significantly associated with a number of trigger foods. The SoB effect was observed in FA patients irrespective of the presence of infantile eczema. Conclusions AWB was predominant in the patients with newly diagnosed food allergies. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan. Between February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology. This study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients. The present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: In developed countries, increasing food allergy prevalence and concern regarding food allergies have been reported. Although the use of complementary and alternative medicine (CAM) for the treatment of allergic diseases has increased in some Western countries, the actual proportion and patterns of CAM use for pediatric food allergies in Japan are still unknown. Methods: Fourteen allergy centers in Japan participated in the study using a questionnaire survey regarding the use of CAM by pediatric patients. A diagnosis of food allergy was made at each hospital by pediatric allergists. Results: Surveys were completed by parents/guardians, and data were collected for a total of 962 pediatric food-allergic patients. Overall, 8.4% of the participants used CAM to treat a food allergy. The major CAM therapies used were herbal teas (22.2%), including several Japanese herbal teas, Chinese herbal medicine (18.5%) and lactic acid bacteria (16%). Among the participants using CAM to treat food allergy, 13.6% thought that the CAM being used was very effective, while 11.1% of participants thought that CAM caused some type of side effect. Conclusions: Our study is the first large-scale national survey regarding the use of CAM in pediatric patients with food allergies in Japan. Unlike in the USA, which has a higher rate of CAM use (17%), approximately 8.4% of food-allergic patients used CAM in Japan. Interestingly, the major types of CAM used in Japan differed from those used in the USA. Cultural differences and food customs may affect the use of CAM. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Diagnosis of food allergy should be based on the observation of allergic symptoms after intake of the suspected food. The oral food challenge test (OFC) is the most reliable clinical procedure for diagnosing food allergy. The OFC is also applied for the diagnosis of tolerance of food allergy. The Japanese Society of Pediatric Allergy and Clinical Immunology issued the 'Japanese Pediatric Guideline for Oral Food Challenge Test in Food Allergy 2009' in April 2009, to provide information on a safe and standardized method for administering the OFC. This review focuses on the clinical applications and procedure for the OFC, based on the Japanese OFC guideline. [ABSTRACT FROM AUTHOR]

Background: The importance of peanut allergy has not been well recognized in Japanese society. IgE antibody to peanut can be, however, detected in patients without clinical peanut allergy. Methods: Clinical characteristics of 14 patients (aged 1-8 years) with peanut allergy were evaluated. IgE antibodies to peanut from patients with and without clinical peanut allergy were compared with those to soybean and other nuts. To examine the role of cross-reactive carbohydrate determinant (CCD) on the clinically false positive detection of peanut IgE, horseradish peroxidase (HRP) and bromelain specific IgE were measured by Uni CAP IgE kit. Inhibition of peanut IgE by HRP was also examined. Results: The patients repeatedly experienced potentially life-threatening symptoms, including anaphylaxis. Sera from patients with peanut allergy had negative or relatively low IgE antibodies to other nuts. However, clinically false positive peanut IgE showed significant correlation-coefficients with soybean, almond, chestnut, pistachio, macadamia and cashew (r = 0.61-1.00). Anti-HRP and anti-bromelain IgE antibodies were detected in the clinically false positive sera, but not in the sera from patients with peanut allergy. Two out of four clinically false positive peanut IgE antibodies were significantly inhibited by HRP. Conclusions: Social education about the features of peanut allergy is needed in Japan. Anti-CCD IgE antibody was suggested to be one of the mechanisms contributing to the false positive detection of peanut IgE. Detection of anti-HRP or anti-bromelain IgE can be a useful tool to recognize the presence of anti-CCD antibodies. [ABSTRACT FROM AUTHOR]

Previous research has produced conflicting evidence on the preventive effects of early introduction of cow's milk protein on cow's milk allergy (CMA). Through a randomized controlled trial, we sought to determine whether the early introduction of cow's milk formula (CMF) could serve as an effective strategy in the primary prevention of CMA in a general population. We recruited newborns from 4 hospitals in Okinawa, Japan. Participants were randomly allocated to ingest at least10 mL of CMF daily (ingestion group) or avoid CMF (avoidance group) between 1 and 2 months of age. In the avoidance group breast-feeding was supplemented with soy formula as needed. Oral food challenge was performed at 6 months of age to assess CMA development. Continuous breast-feeding was recommended for both groups until 6 months of age. We identified 504 infants for randomization into the 2 groups. In all, the parents of 12 participants declined to receive the intervention, and the study sample comprised 491 participants (242 in the ingestion group and 249 in the avoidance group) for a modified intention-to-treat analysis. There were 2 CMA cases (0.8%) among the 242 members of the ingestion group and 17 CMA cases (6.8%) among the 249 participants in the avoidance group (risk ratio = 0.12; 95% CI = 0.01-0.50; P <.001). The risk difference was 6.0% (95% CI = 2.7-9.3). Approximately 70% of the participants in both groups were still being breast-fed at 6 months of age. Daily ingestion of CMF between 1 and 2 months of age prevents CMA development. This strategy does not compete with breast-feeding. [ABSTRACT FROM AUTHOR]

The interval between antigen ingestion may influence the safety of oral food challenge tests (OFCs), especially in patients with severe food allergies. This retrospective chart review of OFCs eliciting objective reactions to wheat, egg, and milk that were performed between April 2012 and January 2021 evaluated an equivalent number of low-dose OFCs performed at 30-, 40-, or 60-min intervals. To avoid the influence of the potential allergy severity of the patients, the prediction scores of all intervals were matched. We evaluated the total symptom score (TS), total ingested dose, and the proportions of severe reactions (TS ≥ 30) and adrenaline use. We analyzed 945 OFCs (wheat, n = 186; egg, n = 561; milk, n = 198). The 60-min OFC had significantly lower TS than the 30- and 40-min OFC methods in wheat (p < 0.001 and p = 0.003, respectively), egg (p < 0.001 for both), and milk (p < 0.001 and p = 0.018, respectively). The total dose in the 60-min method was significantly lower than in the 30-min method (p < 0.001 for all). The proportion of severe reaction (TS ≥ 30) in the 60-min method was significantly lower than that in the 30-min method for the egg and milk OFCs (p = 0.001 and p < 0.001, respectively). There was no difference in the rates of adrenaline injection. The 60-min interval is safer than 30- or 40-min intervals in wheat, egg, and milk OFCs in patients with a low threshold dose for food allergy. [Display omitted] [ABSTRACT FROM AUTHOR]

Little has been reported on how to introduce hen's egg into the diet of children with suspected egg allergy. We compared the efficacy, safety, and parental anxiety of two different dietary instruction methods to introduce egg. Eligible participants were children aged 1–4 years who were positive for egg white IgE, and ovomucoid IgE <3.5 kUA/L. Participants were either naïve in egg consumption or had a history of an immediate, but non-anaphylactic, allergic reaction to egg. After a negative result of baseline 2 g boiled egg white oral food challenge (OFC), participants were randomly assigned to the step-up OFC testing (SOFT) or home incrementing group. The primary outcome was the proportion of participants who were able to ingest 20 g of boiled egg white 6 months after initiation. This study is registered with the University Hospital Medical Information Network clinical trial registry (UMIN000024192). Between September 2016 and August 2018, we randomly allocated 55 participants to the SOFT (n = 33 [60%]) and home incrementing (n = 22 [40%]) groups and analyzed 51 patients. Four patients were excluded because they were lost to follow-up. Thirty-one (96.9%) of 32 participants in the SOFT and 12 (63.2%) of 19 in the home incrementing group achieved the primary outcome (p = 0.003). No serious adverse reactions were observed in either group. Parental anxiety significantly improved during treatment in both groups. The SOFT method was more effective than home incrementing as dietary instruction to introduce egg in children with suspected egg allergy. Image 1 [ABSTRACT FROM AUTHOR]

We examined the feasibility, efficacy and safety of slow low-dose oral immunotherapy (SLOIT) for egg, milk, wheat allergies, with accepted severity-stratified initial and maintenance doses. Children with food allergies defined by low-dose oral food challenges (LD-OFCs) to hen's egg (cumulative protein dose up to 983 mg, n = 133), cow's milk (287 mg, n = 50), and wheat (226 mg, n = 45) were recruited. Participants were divided into two groups [SLOIT and control (complete avoidance]) based on their preferences. Participants who selected SLOIT were instructed to take the safe dose daily, with monthly increases, aiming to increase the dose by 10 times in one year. The primary outcome was the proportion of participants who passed the LD-OFCs following 1 year of therapy. The participants in SLOIT group ingested their antigen 92.9% of the therapy's day on average. The proportion of participants who passed LD-OFCs was 35.9% (61/170) in the SLOIT group and 8.7% (4/46) in the control group (P <.001); no large differences were observed among allergens. Among the subjects who failed LD-OFCs, the median change in the total dose in the LD-OFC was 235% (interquartile range: 100%–512%) in the SLOIT group and 100% (42%–235%) in the control group (P <.001). Provoked allergic symptoms were observed in only 0.58% (280/48,486) per programmed intake and approximately 50% of the SLOIT group did not experience any obvious allergic symptoms throughout therapy. SLOIT showed significant feasibility, efficacy and safety, providing a promising option to manage patients with severe food allergies. Image 1 [ABSTRACT FROM AUTHOR]

Abstract The season of birth and ultraviolet B exposure have been related to the occurrence of food allergy. The levels of vitamin D produced from skin by ultraviolet B exposure might reflect this relationship. Vitamin D is known to induce antimicrobial peptides, protect intestinal flora, enhance the gut epithelial barrier, suppress mast cell activation and IgE synthesis from B cells, and increase the number of tolerogenic dendritic cells and IL-10-producing regulatory T cells. Vitamin D deficiency has been shown to exacerbate sensitization and allergic symptoms in a murine model of food allergy. However, in clinical situations, contradictory observations have been reported regarding the relationship between food allergy and vitamin D deficiency/supplementation. In this review, we have explored the links between food allergy and vitamin D levels. One explanation for the discrepant findings is confounding factors such as race, age, residency, skin color, and epigenetic changes that contribute to vitamin D levels. In addition, the season of birth influences the development of atopic dermatitis, which could lead to food sensitization. Finally, ultraviolet radiation could lead to regulatory T cell expansion and immunosuppression, irrespective of vitamin D status. Based on our current understanding, we believe that correction of vitamin D deficiency by supplementation, appropriate skin care, and sufficient ultraviolet radiation exposure could alter the prognosis of food allergy. To identify potential treatment strategies for food allergy, it is essential to gain a better understanding of the appropriate levels of vitamin D and ultraviolet radiation exposure. [ABSTRACT FROM AUTHOR]

Abstract Background The unintentional usage of adrenaline auto-injectors may cause injury to caregivers or patients. To prevent such incidents, we assessed the causative factors of these incidents. Methods The Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which adrenaline auto-injectors were unintentionally used. One hundred cases were reported from June 2015 to March 2016. We identified the root causes of 70 child and 25 adult cases, separately. Results The incidents occurred with repeated prescriptions as well as the first prescription. Three cases resulted in a failure to administer an adrenaline auto-injector to children with anaphylaxis. Four caregivers used it with improper application (epilepsy or enteritis). Among the child cases, the median age at the time of the incident was 5.5 years (range, 2–14 years). Five children injected the adrenaline auto-injector on their own body trunk. Twenty children were not the allergic patients themselves. Improper management protocol of the device and the child's development were concomitantly involved in most of the cases. A variety of human behaviors were identified as the root causes in the adult cases. At least 34 cases were associated with mix-ups between the actual and training device. Conclusions Health workers should provide sufficient education regarding safety use of adrenaline auto-injector for caregivers tailored to their experience levels at both first and repeated prescriptions. Such education must cover anticipatory behavior based on normal child development. Devices should also be further improved to prevent such incidents. [ABSTRACT FROM AUTHOR]

Background We have proposed a new scoring system (Anaphylaxis SCoring Aichi: ASCA) for a quantitative evaluation of the anaphylactic reaction that is observed in an oral food challenge (OFC). Furthermore, the TS/Pro (Total Score of ASCA/cumulative protein dose) can be a marker to represent the overall severity of a food allergy. We aimed to develop a prediction model for a severe allergic reaction that is provoked in a boiled egg white challenge. Methods We used two separate datasets to develop and validate the prediction model, respectively. The development dataset included 198 OFCs, that tested positive. The validation dataset prospectively included 140 consecutive OFCs, irrespective of the result. A ‘severe reaction’ was defined as a TS/Pro higher than 31 (the median score of the development dataset). A multivariate logistic regression analysis was performed to identify the factors associated with a severe reaction and develop the prediction model. Results The following four factors were independently associated with a severe reaction: ovomucoid specific IgE class (OM-sIgE: 0–6), aged 5 years or over, a complete avoidance of egg, and a total IgE < 1000 IU/mL. Based on these factors, we made a simple scoring prediction model. The model showed good discrimination in a receiver operating characteristic analysis; area under the curve (AUC) = 0.84 in development dataset, AUC = 0.85 in validation dataset. The prediction model significantly improved the AUC in both datasets compared to OM-sIgE alone. Conclusions This simple scoring prediction model was useful for avoiding risky OFC. [ABSTRACT FROM AUTHOR]

The article presents results of study conducted to evaluate the effect of accidental usage of adrenaline auto injector in Japanese children suffering from food allergy.