Background: The adherence to oral immunotherapy (OIT) for food allergies (FA) among children is affected by their perspectives. This study explored the perspectives of children undergoing OIT and identify potential interventions to foster a positive approach to the treatment.

Methods: Self-administered questionnaires and semi-structured interviews were conducted on 66 elementary and junior high school students undergoing OIT. Participants were categorized into two groups based on their adherence to the treatment: a favorable group (with protocol compliance) and a difficult group (with compliance below 30% or OIT discontinued). The assessment criteria encompassed knowledge, motivation, anxiety, aversion, and burden.

Results: In the favorable group (n = 44, median age 9 years), the percentage of knowledge (97.8% vs. 77.3%, P<0.05) and motivation (93.2% vs. 63.6%, P<0.01) was significantly higher than in the difficult group (n = 22, median age 10 years). Although there were no significant differences in anxiety, aversion, and burden between the two groups, over 40% of the children experienced anxiety and aversion even within the favorable group.

Conclusion: To ensure the smooth continuation of OIT, it may be essential to confirm and enhance knowledge and motivation. Additionally, interventions addressing anxiety, aversion, and burden could play a crucial role in facilitating the smooth continuation of OIT.

Background:

In Japan, allergen scratch extract Torii^® (SE) is used as a standard reagent for skin prick tests; however, there is no clarity on the protein content of the extract is not clear.

Methods:

Sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) and immunoblotting were conducted to analyze SE derived from egg white, egg yolk, and cow's milk, and compared to those of raw egg white, raw egg yolk, and cow's milk, respectively.

Results:

The protein content of each SE was found to be lower than that of the respective food sources. SDS-PAGE revealed a band in the egg white SE similar to that in raw egg white, and immunoblotting confirmed the presence of sufficient amounts of ovalbumin and ovomucoid. Egg yolk SE demonstrated trace amounts of ovalbumin and ovomucoid. Conversely, cow's milk SE contained little amount of casein but significant amounts of α-lactalbumin and β-lactoglobulin.

Conclusion:

Egg yolk SE contained trace amounts of egg white components, while cow's milk SE mainly consisted of whey components.

Introduction: This study aimed to identify the characteristics and indicators of food allergy (FA) in preterm infants treated at a perinatal mothers and children's center.

Method: A retrospective investigation of immediate-type FA (hen's eggs, cow's milk, wheat, and soybeans) was conducted using the medical records of infants born between April 1, 2012 and March 31, 2020, who were treated in the Perinatal Mothers and Children's Center of the University of the Ryukyus Hospital and attended the hospital from less than 37 weeks of gestation until the age of 1 year.

Results: From the records of 362 1-year-old children, 23 were found to have immediate-type FA. The causative foods were hen's eggs in 18 children, cow's milk in 4 children, soybeans in 3 children, and wheat in 2 children (including duplications). The prevalence of FA was higher in children born in autumn and winter, children with eczema observed on physical examination, and children with eosinophilia (≥7% and 750/μL) in the neonatal period.

Conclusion: General blood test findings in preterm infants may be useful for predicting the subsequent development of FA. Prevention of skin sensitization by eczema treatment and developmentally appropriate weaning progression are important in preventing the development of FA.

The mechanisms of tolerance induction in food allergies involve the establishment of oral tolerance along with the development of digestive and mucosal barrier functions. When food antigens are degraded to amino acids, their antigenicity disappears and no immune response is elicited. The mucosal barrier is composed of mucus, intestinal epithelial cells, immunoglobulin A, and antimicrobial peptides that block the entry of antigens in the intestinal tract. Oral tolerance is a physiological phenomenon that suppresses the immune response to antigen recognition in the gastrointestinal tract, and is modulated by antigen-presenting cells, regulatory T cells, and inhibitory cytokines. Besides the intestinal tract, the liver and tonsils are other organs that induce immune tolerance; the intestinal microbiota also contributes to the induction of immune tolerance. The mechanisms of oral immunotherapy are complex, involving both acquired and innate immunity, and negative regulation of the immune response by regulatory T cells and interleukin-10 are particularly important. High doses of antigens induce clonal anergy but may enhance intestinal inflammation and allergic reactions and interfere with tolerance. Therefore, more detailed mechanisms must be elucidated to optimize oral immunotherapy protocols and develop new therapies.

Janus kinase inhibitors (JAKi) are small-molecule targeted drugs that modulate disease states by inhibiting the function of JAKs, which are involved in signaling about 40 cytokines and growth factors. JAKi for rheumatoid arthritis showed efficacy comparable to biologic disease-modifying anti-rheumatic drugs and was approved for reimbursement in Japan seven years earlier than atopic dermatitis. Nevertheless, the results of clinical trials and post-marketing surveillance examining long-term safety suggest that JAKi is associated with death, cardiovascular events, malignant tumors, and thrombosis in high-risk patients. In addition, real-world data on JAKi for pediatric rheumatic diseases are not yet precise, as insurance coverage for baricitinib (BARI) was just approved in March 2024 for juvenile idiopathic arthritis with active polyarthritis, which has shown an inadequate response to existing therapies. At the same time, BARI was also approved in Japan for the treatment of pediatric atopic dermatitis in children aged two years and older who have had an inadequate response to existing therapies. Thus, it is hoped that pediatricians in Japan will accumulate experience in safely using JAKi, which has advantages not found in biologics.

TNF inhibitors were the pioneering biologic agents utilized in the management of inflammatory bowel disease (IBD), with some undergoing clinical trials in pediatric populations and approved for use in children. The advent of TNF inhibitors has markedly transformed the treatment landscape for pediatric IBD, demonstrating efficacy not only in ameliorating clinical symptoms but also in addressing growth impairment and other manifestations. In Crohn's disease, treatment guidelines and international recommendations advocate for the precedence of TNF inhibitors over alternative biologic agents. In ulcerative colitis, European guidelines prioritize infliximab, while Japanese protocols encompass a spectrum of biologics and small molecules beyond TNF inhibitors for refractory cases, necessitating personalized treatment decisions accounting for variables such as administration route and onset of efficacy alongside pediatric indications. Internationally, combining infliximab with immunomodulatory agents is advised to mitigate anti-drug antibody formation, typically recommended within approximately 6 months following the initiation of infliximab therapy. Furthermore, caution should be exercised regarding potential dose escalation requirements for TNF agents relative to adult dosing.

Belimumab, a human monoclonal antibody that inhibits the B-lymphocyte stimulator (BLyS), was the first biologic agent approved for treatment of systemic lupus erythematosus (SLE). Elevated serum BLyS levels are observed in patients with SLE. Belimumab inhibits the biological activity of BLyS, which is important for the survival and development of B lymphocytes into antibody-producing mature plasma B cells. Belimumab is indicated for treatment of patients with active SLE receiving standard therapy, such as glucocorticoids and immunosuppressants. The efficacy of belimumab remains unclear in patients with severe active lupus nephritis in Japan. However, in other countries, the combined use of belimumab as initial and/or maintenance therapy is recommended considering its additional benefit in cases of lupus nephritis. Belimumab is a useful biologic agent to achieve dose reduction or enable discontinuation of glucocorticoids in the management of SLE. Future studies should investigate the appropriate timing for the introduction of this useful drug.

Anifrolumab is an anti-type I interferon receptor subunit 1 monoclonal antibody. It is approved for treating systemic lupus erythematosus (SLE) in Japan. Type I interferons are central to developing SLE. Anifrolumab inhibits the type I interferon signaling, which reduces the expression of CD80 and CD83 on dendritic cells, suppresses the survival factors of B cells, inhibits B cell differentiation, and restricts T cell activation. Clinical trials have shown that anifrolumab improves various parameters such as disease activity response, reduction in glucocorticoid dosage, skin disease activity, active joint count, and healing rates. Based on these results, the 2023 update of the EULAR Recommendations lists anifrolumab as one of the treatment options for SLE in patients who have not developed lupus nephritis. It is important to note that anifrolumab is only approved for adults in Japan and is not intended for children.

Following the Japanese Pediatric Guideline for the Treatment and Management of Asthma: JPGL 2020, Chapter 4 in JPGL2023 described the objective tests required for the diagnosis and treatment of pediatric bronchial asthma. The evaluation of the Th2-type response, which is the basic immune abnormality in asthma, is discussed, including serum total IgE level, peripheral blood eosinophil count, allergen-specific IgE antibodies and skin prick test. Practically, evaluation of respiratory function [including spirometry, oscillometry and bronchial hyperresponsiveness test] and fractional exhaled nitric oxide (FeNO) measurement, which are important for diagnosis of asthma, evaluation of severity and therapeutic effect, are described in detail. Since spirometry is the most important test, the principle of measurement, the interpretation of results and the points to be noted in the pediatric patients are explained. Other techniques for evaluation of airway condition and airway inflammation are also introduced.

For the long-term management of pediatric bronchial asthma, the use of pharmacotherapy as well as addressing exacerbation factors and patient education is crucial. Therefore, the title "Pharmacotherapy for Long-term Management" in the JPGL 2020 was changed to "Long-term Management" in the JPGL 2023. The revised points are as follows: setting goals from the perspectives of treatment and management to optimize clinical practice, changing to a long-term cycle of "Review / Assess ", "Adjust", "Treatment", and "Decision", and promoting active participation in care by patients and parents alongside decision-making with healthcare providers. The guidelines have clarified the treatment framework for refractory asthma by specifying the coordination between hospital and clinical practice to ensure appropriate and efficient patient care. In terms of pharmacotherapy, the inclusion of inhaled corticosteroids/long-acting inhaled beta2-agonists in the long-term management plan for children under 5 years was added related to changes in the prescribing information for the combination of fluticasone and salmeterol. Furthermore, the expansion of biologic agents such as anti-TSLP antibodies is reflected by noting comorbidities that guide the selection of formulations to be used. The guidelines also emphasize caution regarding the systemic effects of inhaled corticosteroids.

The "Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2023, (Chapter 6: Risk factors for exacerbations and preventive measures) " better identifies the risk factors for the exacerbation of asthma; these risk factors, which were listed in multiple chapters in JPGL (2020), were collectively identified in a single chapter. In addition, environmental and individual factors were listed separately, and the following individual factors were newly added: history of severe asthma symptoms, abnormal respiratory function tests, and poor adherence/inhalation technique. The explanations for each risk factor have been updated based on new findings, and new information on when the risk factors should be evaluated was added. Accordingly, this paper highlights and explains the key points of these revisions.