Purpose : Our aim was to analyze the usage of adrenaline auto-injectors (AAIs) for anaphylaxis in children with food allergy who were living in a non-metropolitan area.

 Methods : A retrospective analysis of 322 AAI prescriptions for 124 consecutive patients (79 boys, 45 girls) was conducted.

 Results : Of the patients, 124 (100%) had food allergies, 120 (97%) had experienced anaphylaxis, and 36 (29%) weighed<15 kg. After administration of the AAI prescription, anaphylactic reactions of grade 3 or 4 were triggered in 34 patients (27%) on a total of 55 occasions. There were no side effects after AAI administration in all 30 cases, including in six patients who weighed<15 kg. A factor that was significantly associated with AAI prescription was residing outside Kumamoto city at a distance≥10 km to a hospital emergency room (ER) (p<0.01). Patient background, anaphylaxis frequency, and AAI administration rate were independent of distance to an ER.

 Discussion : The distance to an ER had an impact on AAI prescriptions in our hospital, but did not influence the rate of AAI use during anaphylaxis. More appropriate instructions are necessary to increase the use of AAI for anaphylaxis.

 Objective : We aimed to examine the prevalence of allergic disease and the preventative measures against allergic emergencies among kindergartens and nurseries in Tokyo to identify the issues for improving the management of these diseases in kindergartens and nurseries.

 Methods : We mailed a self-administered anonymous questionnaire to a total of 7,405 kindergartens and nurseries in Tokyo and collected the response in September 2014.

 Results : We obtained answers from 5,348 institutions (response rate : 72.2%), which showed the following prevalence : food allergy 6.3%, bronchial asthma 3.6%, atopic dermatitis 2.9%, allergic rhinitis 2.3%, allergic conjunctivitis 0.9%, and anaphylaxis 0.6%. Eighty point five percent of the institutions had young children with food allergy, and 19.0% had experienced a child having food allergic reactions on the premises. The reaction was the first episode in 64.9% (658 institutions) of the cases and caused by an accidental ingestion in 34.1% (346 institutions) of the cases.

 Conclusions : Compared to the survey conducted by Tokyo Metropolitan in 2009, the numbers of young children with food allergy, allergic rhinitis, allergic conjunctivitis and food anaphylaxis had all increased. For management of food allergy, it is essential to obligate the submission of an accurate allergy management plan, ensure that parents and families feed their children a variety of foods before starting kindergartens and nurseries to avoid the first exposure to a possible food allergen, determine the cause of an accidental ingestion, and to prepare for management of food allergy emergencies.

 Background : Infants with atopic dermatitis have a high risk of having egg allergy. In this study, safety of baby food containing ovomucoid-reduced egg white for infants and children with atopic dermatitis was evaluated.

 Methods : Using a bottle of baby food containing ovomucoid-reduced egg white, an open oral food challenge test was conducted on infants and children with atopic dermatitis and without previous exposure to egg white.

 Results : Forty-six subjects [24 boys, 22 girls ; median age 10.0 months (9-12 months) ] were included in the study. The median egg white-specific IgE levels (10.1 U_A/ml), median ovomucoid-specific IgE levels (0.21 U_A/ml), and median serum thymus and activation-regulated chemokine (1553 pg/ml) were examined. Forty-three subjects (93.4%) could ingest a complete bottle of baby food without any allergic reactions. Although three subjects displayed a slight skin symptom, they could ingest a complete bottle of baby food without any symptoms in a retest.

 Conclusion : It is suggested that baby food containing ovomucoid-reduced egg white is safe for infants and children with atopic dermatitis. The oral food challenge test for infants and children with high levels of ovomucoid-specific IgE needs to be conducted in the future.

 Background and Aim : We developed an inpatient skin care educational program for caregivers of children with AD refractory to outpatient treatments. We evaluated the usefulness of the skin care techniques taught in this program for caregivers and determined whether the improved skin condition of the children with AD could be maintained after discharge.

 Method : The subjects were 49 caregivers of children with refractory AD. In our three-day/two-night skin care educational program, we trained the caregivers on the proper bathing and topical application techniques. We rated the eczema severity by calculating the Eczema Area and Severity Index (EASI). At discharge, we conducted a questionnaire survey of the caregivers.

 Results : The mean EASI scores were 28.2 on admission, 15.6 at discharge, and 8.9 at one month after discharge. At admission, roughly 80% of the caregivers faced difficulty in the precise use of topical application techniques, such as proper application of the topical corticosteroid to the affected eczematous skin and use of appropriate amounts of the topical agents. However, at discharge, they were able to successfully apply these techniques. In the questionnaire survey performed at discharge, 85% of the caregivers admitted to having had a poor understanding about the appropriate amounts of the topical agents.

 Conclusion : For children with refractory AD, the caregivers could learn and master the skills of skin care through our inpatient program. The improved condition of the skin of the children was still maintained at the evaluation conducted a month after completion of the program.

 The number of food allergy workshops, which teach teachers, childcare workers, and dietitians about food allergies and emergency care, has increased in recent years. We analyzed the efficacy of food allergy workshops and issues raised through workshops held at schools, elementary schools, nursery schools and municipal offices 13 times, from May 2014 to August 2015, and distributed questionnaires to 1356 teachers, childcare workers, and dietitians before and after the workshops. The results showed that the number of participants who were confident about using Epipen^® increased. After the workshops, there were some positive opinions, for example “I have deepened my understanding” and “I recognize the necessity for the workshops and manual”. But there were requests and issues too. For example, “I want to see concrete examples” and “I feel uneasy about using Epipen^®”.

 The workshops for the staff of schools, elementary schools and nursery schools were effective. But we should reconsider the contents of the workshops. The questionnaires were effective methods for revealing problems with the workshops.

 Atopic dermatitis (AD) develops different clinical symptoms, progress, and treatment response during early infancy and after childhood. After the childhood period, itching precedes appearance of dermatitis, followed by formation of lichenoid chronic dermatitis at the same site. Thus, controlling itching is important in the management of AD. In many cases, itching increases in the evening when tension on the sympathetic nerve decreased. Hypersensitivity to various external stimuli can cause itching should be considered in the management of itch in AD. Heat and sweating are thought to especially exacerbate itching. Factors causing itching, such as cytokines and chemical messengers, induce itching mainly by stimulating the nerve. To control itching induced by environmental factors such as heat, treatment for dermatitis should be considered firstly. In the background of itching exacerbated by sweating, we should pay attention on the negative impact of excess sweat on skin homeostasis, and recommend the patients to wipe off the excess sweat on the skin properly. At the same time, skin inflammation should be controlled so that appropriate amount of sweat can be secreted. Visual and auditory stimulation also can induce itching, so called “contagious itch”. This type of itch can be observed characteristically in in patients with AD.

 The development of molecular targeted therapy for asthma was initiated from inhibiting IgE or IL-5 signaling, which activates effector function cells, including mast cells or eosinophils. To date in 2017, anti-IgE omalizumab and anti-IL-5 antibody mepolizumab is clinically available in Japan. United States Food and Drug Administration has already approved another anti-IL-5 antibody, reslizumab. In addition, clinical efficacy of anti-IL-5Rα antibody benralizumab, which is reported to have ADCC (antibody-dependent cell-mediated cytotoxicity) activity, has been proved in two phase 3 studies. IL-13 in addition to IL-5, is an important cytokine derived from Th2 cells and type 2 innate lymphoid cells. Anti IL-4Rα antibody, which inhibits both IL-4 and IL-13 signaling, is more promising than antibodies targeting only IL-13. Those antibodies are in phase 2b or 3 trials.

 More recently, the strategies targeting Th2 differentiation or activation including CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) inhibitor, TSLP (thymic stromal lymphopoietin) antibody, and TLR (Toll-like receptor) ligands are under investigation. The position of those molecules is more upstream of allergic airway inflammation. But clinical trials concerning those molecules are still in phase 1 or 2, and further investigations showing the additive effect on ICS are required.

 Anti-IL-5 should be used only for eosinophilic asthma based on previous studies. As molecular targeted therapies should be tailored to the endotypes, further refinement of specific biomarkers is needed for optimal treatment.

1. A food allergy is defined as “a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to a given food”.

2. When food or its components cause the allergic symptoms, the term “food allergy” is applied regardless the route of allergen exposure.

3. Food allergies are immunologically classified into IgE-mediated reactions and non-IgE-mediated reactions. Based on the time course, it is divided into immediate reactions and non-immediate reactions. Most of the IgE-mediated reactions cause immediate reaction, but it is not always the case.

4. Symptoms provoked by food allergy include skin, mucosal, respiratory, gastrointestinal, nervous and cardiac organs.

5. Anaphylaxis is defined as “severe hypersensitivity reaction that may cause a life-threatening risk with systemic symptoms induced at several organs”. Anaphylaxis shock is that accompanied by reduced blood pressure or incontinence.

 Since food is a beneficial foreign substance for organisms, oral immune tolerance is induced and excessive immune response is suppressed. Such failure of oral immune tolerance is considered a pathogenic mechanism of food allergies. On the other hand, sensitization to food allergens is known to be induced by multiple exposure routes including intrathecal sensitization, transintestinal sensitization, respiratory tract sensitization, and transcutaneous sensitization, and their role in the development of food allergies has garnered attention.

 In terms of IgE-dependent allergies, IgE is cross-linked via the binding of multiple allergen-specific IgE on mast cells and allergens, inducing the degranulation of chemical mediators and the production of lipid mediators, etc. Regarding the pathology of non-IgE-dependent allergies, specific lymphocytes are thought to play an important role in the pathology ; however, the details thereof remain unclarified.

 Many patients with immediate-type food allergies in their childhood acquire resistance as they grow. The development of digestive functions of the digestive tract, physicochemical defense mechanisms, and oral immune tolerance mechanisms due to growth are considered to be mechanisms of acquiring natural tolerance.

 It is expected that the pathology of food allergies will be further clarified, with approaches aiming at the prevention of disease development and induction of remission to be clinically applied in the near future.

 Epidemiology and natural history of food allergy was described in Chapter 3 in Japanese Pediatric Guideline for Food Allergy 2016 (JPGFA2016). Herein, the variations from previous guideline and the new added have been explained. In particular, the nationwide monitoring 2011 surveillance about immediate type of food allergy was described. Regarding allergy march, new related literatures were extracted and described on allergy march starting from food allergy.

 Several studies on risk factors for food allergy (FA) onset have reported about family history, genetic predisposition, skin barrier function, and season of birth. The presence of atopic dermatitis is especially an important risk factor. With respect to prevention of FA, guidelines do not recommend food elimination as a preventive measure in pregnant and lactating mothers. Additionally, the delay in the introduction of specific foods into the diet of high-risk infants is not recommended because it does not reduce the risk of FA onset. There are both positive and negative reports on the impact of exclusive breastfeeding in preventing FAs, and sufficient evidence does not exist to support either. As a compromised skin barrier and the presence of dermatitis constitute percutaneous sensitization risk to food antigens, the possibility that skin care regimens aimed towards active eczema control against atopic dermatitis can decrease allergen sensitization and subsequent allergy march has been considered ; however, at present, evidence supporting this possibility is scarce.

 Background : In children with bronchial asthma that is poorly controlled despite long-term inhaled corticosteroids (ICS), whether increased dose ICS is superior to or inferior to the addition of long-acting β₂ agonists (LABA) to ICS (denoted here as ICS/LABA) is unclear. Methods : Randomized controlled trials (RCTs) that involved pediatric patients with bronchial asthma and that were published prior to March 2016 were systematically reviewed. Acute exacerbations of asthma requiring use of oral corticosteroids served as a primary outcome measure, and acute exacerbations requiring hospital admission, visits to the emergency department, dropouts from trials, respiratory function, symptoms, use of short-acting β₂ agonists, and adverse events served as secondary outcome measures. Results : Eight RCTs were reviewed. Increased dose ICS and ICS/LABA did not differ significantly in terms of preventing acute exacerbations that required use of oral corticosteroids. Increased dose ICS and ICS/LABA did not differ significantly in terms of preventing acute asthma exacerbations requiring hospital admission, preventing visits to the emergency department, improving the Asthma Symptoms Score, or preventing adverse reactions. ICS/LABA resulted in better respiratory function and a greater percentage increase in height. Conclusion : At the current point in time, there is no clear indication whether increased dose ICS is superior to or inferior to ICS/LABA.

 Inhaled corticosteroids (ICS) are recommended as a first-line therapy for children with persistent asthma in Japanese and worldwide asthma guidelines. However, there are several studies reporting its effect on growth. We reviewed the evidence of growth suppression by ICS in previously published randomized controlled trials evaluating this effect.

 Twenty five randomized controlled trials comparing daily use of 6 types of ICS versus either placebo or non-steroid drugs were analyzed. Four were conducted among children younger than 5 years of age. Others were among children aging 5 to 18. There was 0.48 cm/year of linear growth suppression among the ICS treated group during the first year of treatment compared to the placebo group. The magnitude of ICS-related growth reduction differed by the type of drug. There was less or no growth suppression from the second year of treatment. However, a follow up assessment of adult height for one trial showed a significant decrease of 1.2 cm in the ICS treated group. Evidence provided by this review suggests the regular use of ICS can cause growth suppression in children with persistent asthma, which underscores the importance of the correct diagnosis and the optimum dose of ICS to maintain effective control of asthma.

 Inhaled corticosteroids (ICS) are a cornerstone of treatment in long-term management of pediatric asthma in Japanese and worldwide asthma guidelines. Recent studies have suggested that intermittent use of ICS is effective in management of children with persistent asthma. We reviewed the evidence for the efficacy of intermittent ICS for persistent asthma in children in published randomized controlled trials.

 Five randomized controlled trials of intermittent ICS versus placebo for persistent asthma in 490 preschool and 145 school-aged children were analyzed. The results showed that use of intermittent ICS at onset of early symptoms reduced the likelihood of requiring rescue oral corticosteroids, compared to the placebo group. However, there were no significant differences in hospitalization rates, adverse events and quality of life between the two groups. More studies are needed to evaluate the best dose and regimen for ICS in this patient population.

 Results to date suggest that intermittent use of ICS should not be recommended as standard treatment for children with persistent asthma.

 Aims : To evaluate the effectiveness of leukotriene receptor antagonist (LTRA) add-on therapy to inhaled corticosteroids in pediatric/adolescent patients with uncontrolled asthma.

 Methods : A systematic review (SR) was performed for randomized controlled trials including patients aged 1-20 years. The primary endpoint of this SR was the number of patients with acute exacerbation requiring systemic corticosteroid during treatment.

 Results : Three articles met the criteria for the SR. The recruitment age in all of the selected articles was>6 years old. ICS medications included budesonide 200-400μg/day or fluticasone propionate 200μg/day, and montelukast was used as an LTRA in the studies. There were no significant differences in the primary endpoint of asthma exacerbation (n=601, relative risk 0.93, 95% confidence interval 0.46-1.87).

 Conclusion : LTRA add-on therapy in patients treated with ICS does not appear to prevent asthma exacerbations. Therefore, we do not uniformly recommend the use of LTRA as ICS add-on therapy. However, an LTRA add-on may be useful in younger children with infection-induced asthma exacerbations or in certain phenotypes of asthma.