We present the case of a 7-year-old boy, with untreated mild-to-moderate persistent bronchial asthma since infancy. He was brought to his previous hospital with respiratory failure and impaired consciousness, and thereafter transferred to our hospital for intensive care. The parents initially refused consent for exclusive corticosteroid treatment; however, they consented after we explained that corticosteroids constitute essential life-saving treatment. Besides the systemic administration of steroids, we initiated ventilatory management under muscle relaxation with rocuronium, repeated inhalational procaterol administration, and continuous magnesium sulfate intravenous infusion. Although the parents had been hoping for early discontinuation of corticosteroid use, after daily patient education, they agreed that corticosteroid use was acceptable for only acute exacerbations. Eventually, however, they were regretful about the earlier nonuse of corticosteroids, and accepted corticosteroids despite the conflict. He was extubated on the 6th day, and transferred to the referring hospital, which was equipped with an outpatient allergy clinic, to enable long-term management. He continued to receive inhalational corticosteroids for the next 6 months, without acute exacerbations. Although a near-fatal bronchial asthma exacerbation can trigger corticosteroid acceptance, it is important to assuage the parents' feelings about corticosteroid therapy that is started without sufficient time to foster acceptance.

In Japan, there is only one existing report on hazelnut oral food challenge (oral food challenge: OFC) in children, which indicated a positivity rate of 10%. The present study aimed to compile data on hazelnut OFC conducted in our department and evaluate its clinical characteristics. We included hazelnut OFC conducted from January 2013 to December 2022, targeting loading doses of 1 g and 10 g. We retrospectively examined the relationship among OFC outcomes, patient demographics, and hazelnut-specific IgE levels using medical records. The study included 96 participants, with 48 participants each in the 1 g and 10 g loading groups. The positivity rates for OFC were 19% for the 1 g group and 15% for the 10 g group, while the anaphylaxis induction rates were 6% and 4%, respectively. Univariate analysis did not identify any factors significantly associated with OFC positivity. Furthermore, it was not possible to calculate a 95% positive predictive value for hazelnut-specific IgE levels. Hazelnut OFC can cause severe symptoms, and should be performed with adequate preparation.

Purpose: To conduct a survey on the current situation regarding the management of food allergies in nursery schools.

Methods: In 2023, questionnaires were sent by e-mail to 450 nursery schools, etc. in Kobe.

Results: 135 facilities responded. 112 facilities had children with food allergies. Food was prepared in 85.9% of the facilities, and 93.2% of the 132 facilities provided foods with allergens omitted for children with allergies. The most allergen foods were hen's eggs, milk, walnuts, peanuts, fruits, wheats. Children with restrictions on soup stock, miso, seasonings, etc. were found in 14 facilities. The most common problem in dealing with food allergies was 'safety management'. On the other hand, 38.9% of dietitians answered, 'nutritional balance'. 71 facilities had experience with misfed foods, with differences depending on the number of children in school and the number of children with food allergies (P=0.04). Information sharing between cooks and caregivers was mentioned as one way of dealing with misfed food.

Conclusion: Healthcare professionals need to support safety management in nursery schools and provide dietary and nutritional guidance taking into account nutritional deficiencies in the daily diet.

【Background】Food protein-induced enterocolitis syndrome (FPIES) incidence has recently increased worldwide. In this study, we elucidated the clinical features of FPIES.

【Method】We enrolled patients who met the international consensus diagnostic criteria among pediatric patients suspected of FPIES for 13 years. We retrospectively analyzed the offending foods, clinical results, and clinical course.

【Results】We included 35 patients in this study. Vomiting was the most frequent symptom (100%), followed by lethargy, pallor, and diarrhea. One patient reacted to multiple triggers. We identified 36 offending foods, hen's egg was the most common (21 cases). Although all cases of hen's egg reacted to that egg yolk, none reacted only to egg white. FPIES case numbers, especially those of hen's egg, have increased since 2017. Twelve of the 18 patients (67%) with egg yolk FPIES achieved tolerance, 50% tolerance at a median age of 27 months.

【Conclusion】In Japan, hen's egg, especially egg yolk, FPIES has recently been increasing. Half of patients with egg yolk FPIES might achieve tolerance by the age of 24 months. We suggest regular oral food challenge tests to avoid unnecessary elimination.

Oral immunotherapy (OIT) is widely performed in Japan, Europe, and north America, although some differences exist between Japan and other countries regarding target of subjects and methods.

In other countries, an oral food challenge (OFC) is not always conducted before OIT. Furthermore, stepwise OFC, which begins with a low-dose to evaluate threshold, has rarely been performed. The severity of participants differed from that in Japan.

Although OIT combined with anti-IgE antibodies has improved safety overseas, the majority of efficacy is desensitization, rather than sustained unresponsiveness (SU).

Palforzia is covered by health insurance in Europe and the United States; however, SU has not been evaluated, and issues, such as safety and continuation of treatment, remain unresolved. Currently, there are no prospects for Palforzia's approval in Japan.

In Japan, OIT is typically administered at a low maintenance dose, which has safely induced low-dose desensitization. Long-term low-dose OIT reaches to medium- and full-dose SU over time, and provides a preventive effect against accidental ingestion.

Although safety has improved under the new protocol, achieving SU in the short term remains nearly impossible. It is important to adjust the protocol individually and to explain necessity of long-term treatment to subjects and their guardians.

What oral immunotherapy and dietary advice have in common is that attending physicians need to clearly dictate the amounts to be eaten and the specific methods while also being responsible for the results. It is reasonable to consider oral immunotherapy as the riskier version of dietary advice. To ensure safety, the loading dose must be set at a safe enough range for the threshold of symptom onset, and guidance and safety measures must be provided for home treatment. If complete elimination is prolonged, the intake of the causative food becomes unnatural, and even if the patient is medically able to eat the food, social and psychological factors may prevent the patient from continuing to eat it, so tolerance cannot be acquired. The attending physician must fight against time and come up with a natural process that avoids complete elimination as soon as possible, allowing the patient to naturally and safely start age-appropriate intake as soon as possible, before the case becomes "a case in which early acquisition of tolerance cannot be expected with a natural process."

Although some reports have been published that present real-world oral immunotherapy (OIT) data on the use of the peanut OIT drug PALFORZIA^®, these studies are difficult to reference in Japan because the symptom-provoking threshold has not been confirmed by oral food challenge (OFC) before OIT. A total of 259 patients (including participants of slow low-dose OIT (SLOIT) trial and excluded patients due to too severe) diagnosed with a severe allergy (symptom-provoking cumulative dose of boiled egg whites, udon noodles < 8.7 g, or milk < 8.7 mL) were enrolled in this analysis. We surveyed the desensitized amount of antigen approximately nine years after the OFCs. The number of patients who achieved full-dose desensitization (one hen's egg, 200 mL milk, and 200 g udon noodles) was 94/148 (63.5%) for hen's eggs, 31/60 (51.7%) for cow's milk, and 40/51 (78.4%) for wheat. Among them, lower proportions of patients whose allergies were initially considered too severe (hen's eggs 56.3%, milk 27.3%, and wheat 66.7%), those who initially did not choose SLOIT (hen's eggs 51.7%, milk 33.3%, and wheat 60.0%), and those who initially chose SLOIT but could not adhere to the planned regimen (hen's eggs 55.6%, milk 44.4%, and wheat 63.6%) achieved full-dose desensitization. Exercise-induced allergic reactions on desensitization were observed in 1/94 patients (1.1%) with hen's eggs, 6/31 (19.4%) with milk, and 8/40 (20%) with wheat.

The strategy to prevent the onset of food allergies has shifted from "delayed introduction" to "no delayed introduction" to "early introduction" of allergenic foods. The early introduction of hen's egg and peanut has shown to be effective in reducing the risk of food allergies in some randomized controlled trials; and a degree of effectiveness has also been reported in the real world. However, there are increasing reports of anaphylaxis due to food allergies in infants, which underscore the need to devise safer and more practical infant feeding strategies. Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent studies have demonstrated that continued regular consumption of allergenic foods after early introduction is important for preventing the onset of food allergies. Further research is needed that takes into consideration who should be targeted for intervention and who should undergo screening tests.

This review offers a summary of the latest findings for preventing allergies through skin-related measures. It is advisable to maintain the traditional Japanese practice of bathing and cleansing for skin hygiene. For infants at high risk, using moisturizers from the neonatal stage may help delay the onset of atopic dermatitis (AD), assuming that high-quality moisturizers are chosen. Although it may not be possible to entirely prevent the onset of AD, postponing its emergence could potentially lessen the likelihood of developing food allergies. When addressing eczema, prompt intervention is essential. By targeting underlying subclinical skin inflammation with early and consistent treatment and achieving effective control of skin conditions, the risk of developing egg allergy may be reduced. It is crucial to address skin concerns and understand that eczema requires more than just moisturizers for effective treatment. Given that skin interventions alone cannot guarantee complete prevention, it is vital to adopt a multi-faceted approach that includes oral interventions as part of a holistic prevention plan.

The majority of food allergens are proteins that possess multiple IgE binding epitopes within their complex macromolecular structures. In contrast, low-molecular-weight substances are regarded as less allergenic due to their simple structures, which render them less likely to elicit an IgE-mediated immune response. Nevertheless, there have been rare instances of allergic reactions documented in individuals who have ingested foods containing low-molecular-weight substances, such as sugar alcohol erythritol or the polysaccharide pectin. These low-molecular-weight non-protein allergens are commonly utilized as food ingredients or as additives and are often not labeled as ingredients, which makes it challenging to identify them as the causative agents of allergic symptoms. The detection of specific IgE to these substances is challenging due to the difficulty in immobilizing them in the assay system. However, skin tests and basophil activation tests may offer a potential solution. This review will focus on non-protein allergens, with a particular emphasis on erythritol and pectin, and will endeavor to provide a useful clue to diagnose these "rare and underrecognized" allergies.

The N-terminal vicilin protein, a seed storage protein, which is characterized by a unique cysteine sequence, has garnered attention as a potential allergen. To understand the role of this new protein family in the pathology of food allergies and its possible clinical application as an allergen component, it is essential to evaluate the antigenicity of immunoglobulin E epitopes and the protein itself based on resistance to heat and digestion. In this paper, we clarify the recently reported allergenic and protein characteristics of the N-terminal vicilin protein and discuss its potential application as a clinically relevant allergen component based on its relevance to food allergy.

Ovalbumin and ovomucoid, the major allergens in hen eggs, are present in the egg white. The allergenicity and IgE epitopes of these proteins have been extensively studied. Although the allergenicity of egg proteins decreases with heating, ovomucoid is thermotolerant, retaining its allergenicity even after heating. Recently, baked eggs have been increasingly used in clinical practice to some patients, who had an allergic symptom by heated eggs. However, allergenicity of egg bolos does not decrease even after sufficient baking. Although denaturation has been considered important for the hypoallergenicity of egg proteins, we hypothesized that decreased solubility is more important for the hypoallergenicity of egg proteins. To verify this, we analyzed the heat-induced changes in egg white proteins. In this paper, we summarize our findings on the protein solubility of boiled eggs, which was inspired by an analysis of the allergenicity of baked eggs.

Recently, we have learned that the antibody-mediated PD-1 blockade in cancer patients elicits immune reactions against mutated proteins derived from the mutated genome of cancer cells. This implies that PD-1 inhibits immune reactions against the mutant antigens originated from the mutated genome in cancer patients. Then, why does PD-1 have to cancel such cancer cell-specific immune reactions? Is PD-1 on our side, or on the side of cancer cells? We know that PD-1 is a negative regulator of immune reactions, but what kind of immune reactions are negatively regulated by PD-1? In order to answer these questions, I first review the history of the PD-1 research briefly. Then, I present a new hypothesis about the physiological function(s) of PD-1 and try to test its validity by performing a couple of novel experiments.

Evidence-based medicine (EBM) is "decision-making for better patient care that integrates current evidence, clinical expertise, patients' preferences and values and circumstances". It is important to be aware of the distinction between evidence as research findings and EBM, which is comprehensive decision-making that takes into account the diversity and individuality of clinical situations while respecting evidence as a general theory. Clinical practice guidelines are "a document that evaluates the total body of evidence through a systematic review and presents recommendations that are considered optimal, taking into account the balance of benefits and harms, in order to support decision making by healthcare users and providers on important health-related issues," and is useful in the practice of EBM. Shared decision-making (SDM), which has been attracting attention in recent years, is "a process in which the patient and the health care provider, through dialogue, decide on a treatment plan that is acceptable to the patient, based on the patient's own preferences and values, research evidence, and the clinical expertise" and requires understanding in relation to the above definition of EBM with perspective of clinical ethics.