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Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion. A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were −73.5% at week 4, −81.7% at week 28, and −81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%–95.2%). Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD. [ABSTRACT FROM AUTHOR]

This study investigated the potential link between early childhood allergic diseases and neurodevelopmental milestone attainment during the first 3 years of life. Utilizing data from a large-scale prospective birth cohort study in Japan, encompassing 87,986 children, we examined physician-diagnosed and caregiver-reported allergic conditions, including atopic dermatitis (AD), asthma, and food allergy (FA). Neurodevelopmental milestones were assessed using the Ages and Stages Questionnaires at 1, 1.5, 2, 2.5, and 3 years of age. Stabilized inverse probability-weighted generalized estimating equation models were employed to estimate odds ratios (ORs). Our analysis revealed no significant association of AD and asthma with delay in communication, gross motor, fine motor, problem-solving, and personal-social skills during the initial 3 years of life. However, children with FA showed an increased likelihood of experiencing gross motor delay compared with that shown by those without FA (weighted adjusted OR: 1.14). Despite this, no significant association of FA with other developmental domains was observed. Early childhood allergies may not influence neurodevelopmental delays. However, there is a potential association between FA and delays, specifically in gross motor skills, that warrants routine developmental monitoring and additional investigations., (© 2024. The Author(s).)

Previous epidemiological studies have reported an increased risk of anemia in people with allergic disorders. However, previous studies have followed a cross-sectional design. The aim of this study was to investigate the association between the two conditions with a cohort dataset. We used data of 80,943 children in the Japan Environment and Children's Study, the largest birth cohort in Japan. The association between anemia and allergic disorders was evaluated with a logistic regression model and propensity score analysis. After adjusting for potential confounders, children with asthma (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.32-2.60), atopic dermatitis (OR, 2.18; 95% CI, 1.66-2.85), allergic rhinitis (OR, 1.35; 95% CI, 1.05-1.74), allergic rhinoconjunctivitis (OR, 2.95; 95% CI, 1.91-4.54), and food allergies (OR, 1.92; 95% CI, 1.44-2.56) at 2 years of age predicted high odds of developing anemia in the next year. Any allergy at 2 years of age was associated with an increased risk of anemia at the age of 3 years (OR, 1.80; 95% CI, 1.41-2.29). The findings remained stable in the propensity score analysis. Results suggest that allergic diseases were related to caregiver-reported anemia in children.

Introduction: Osteomalacia is caused by an increase in the number of osteoids owing to mineralization failure. There are various causes of osteomalacia, such as hypophosphatemia due to excess production of fibroblast growth factor 23, vitamin D deficiency, insufficient vitamin D action, and renal tubular disorders., Patient Concerns: A 53-year-old man with bone pain and gait disturbance was referred to our institution. At the age of 35, he developed atopic dermatitis. He had eyesight deterioration due to atopic cataracts when he was 37 years old. Subsequently, he stayed home all the time, and his eating habits were unbalanced for a long period of time. Although he had atopic dermatitis, he did not take allergen-free diets, and he did not use sunscreen. Furthermore, when he was 43 years old, he failed to flex his legs and suffered gait disturbance., Diagnosis: Hypocalcemia and hypophosphatemia were observed as follow: calcium, 5.5 mg/dL; adjusted calcium, 6.9 mg/dL; inorganic phosphorous, 1.9 mg/dL. In addition, intact parathyroid hormone levels were as high as 277.4 pg/mL, and 1, 25-(OH)2 vitamin D and 25-(OH) vitamin D levels were markedly reduced: 1, 25-(OH)2 vitamin D, ≤4 pg/mL; 25-(OH) vitamin D, 11.0 ng/mL. Fibroblast growth factor 23 levels did not increase. Alkaline phosphatase (ALP) and bone-type ALP (BAP) levels were high: ALP, 784 U/L; BAP, 159.2 μg/L (reference range: 3.7-20.9 μg/L). Based on these findings, we diagnosed this patient with vitamin D-deficient osteomalacia triggered by long-term social withdrawal and an unbalanced diet., Interventions and Outcomes: After hospitalization, to treat vitamin D-deficient osteomalacia, we started to administer 1 μg/day of alfacalcidol and 3 g/day of calcium lactate. Approximately one month later, 1,25-(OH)2 vitamin D levels increased to 214 pg/mL. Consequently, calcium and inorganic phosphorus were also increased up to 7.8 mg/dL and 3.9 mg/dL, respectively, and intact parathyroid hormone was decreased to 132.0 pg/mL., Conclusions: We should bear in mind the possibility of osteomalacia triggered by social withdrawal and vitamin D deficiency even in middle-aged subjects., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Inclusion of female authors has been noted as potentially beneficial in the development of medical guidelines. Japanese professional committees representing allergic subspecialties develop practical guidelines with recommendations to caregivers, but these committees may be influenced by their gender composition. The objective of our study was to examine the influence of gender in developing pediatric allergic disease guidelines in Japan from 1999 to 2020., Methods: We examined the gender parities among the guideline committee members in allergic rhinitis, atopic dermatitis, bronchial asthma, and food allergy guidelines in Japan. We examined the gender composition of the committees, annual trends, and differences in guideline content., Results: The median proportion of women members among the 22 guidelines committees was 6.6% (range: 0%-27.3%). The analysis of the quadrant period did not show a significant increase in the proportion of female members. The food allergy group had a significantly higher proportion of female members than other guidelines (P < 0.01), but the proportion decreased from 25% to 14.3% during the observation period. For the pediatric asthma guidelines, the proportion of female committee members decreased from 5.3% in the 2000 version to 0% in the most recent revision in 2017., Conclusions: The proportion of women on the committees that develop pediatric guidelines continues to be low and has not improved over the past 20 years., (© 2021 Japan Pediatric Society.)

Aim: To examine the association between maternal caffeine intake during pregnancy and the development of food allergy in young Japanese children up to 3 years of age., Methods: The study involved 1522 mother-child pairs. Data on maternal caffeine intake during pregnancy were assessed with a validated diet history questionnaire. Food allergy was defined by a self-reported claim of having a physicians' diagnosis of food allergy or of having an acute reaction to a food., Results: Compared with the lowest tertile of maternal caffeine intake during pregnancy, the second tertile, but not the highest tertile, was significantly associated with an increased risk of food allergy. Further adjustment on suspicion or diagnosis of atopic eczema at around 4 months postpartum in a follow-up survey did not substantially change the association between maternal caffeine intake during pregnancy and the risk of food allergy in children: further adjusted hazard ratios (95% confidence intervals) for the second (T2), the highest tertiles (T3) and the second and the highest tertiles combined (T2 + T3) were 1.46 (1.10-1.96), 1.16 (0.85-1.56) and 1.31 (1.01-1.70), respectively., Conclusions: Our findings suggest that maternal caffeine intake during pregnancy may be positively associated with the risk of food allergy in children., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

The bacterium Staphylococcus aureus, which colonizes healthy human skin, may cause diseases, such as atopic dermatitis (AD). Treatment for such AD cases involves antibiotic use; however, alternate treatments are preferred owing to the development of antimicrobial resistance. This study aimed to characterize the novel bacteriophage SaGU1 as a potential agent for phage therapy to treat S. aureus infections. SaGU1 that infects S. aureus strains previously isolated from the skin of patients with AD was screened from sewage samples in Gifu, Japan. Its genome was sequenced and analyzed using bioinformatics tools, and the morphology, lytic activity, stability, and host range of the phage were determined. The SaGU1 genome was 140,909 bp with an average GC content of 30.2%. The viral chromosome contained 225 putative protein-coding genes and four tRNA genes, carrying neither toxic nor antibiotic resistance genes. Electron microscopy analysis revealed that SaGU1 belongs to the Myoviridae family. Stability tests showed that SaGU1 was heat-stable under physiological and acidic conditions. Host range testing revealed that SaGU1 can infect a broad range of S. aureus clinical isolates present on the skin of AD patients, whereas it did not kill strains of Staphylococcus epidermidis, which are symbiotic resident bacteria on human skin. Hence, our data suggest that SaGU1 is a potential candidate for developing a phage therapy to treat AD caused by pathogenic S. aureus.

Background: The Harmonising Outcome Measures for Eczema (HOME) initiative has agreed that quality of life should be measured in all atopic eczema clinical trials. Various candidate instruments exist for this domain but their content validity in atopic eczema is largely unclear., Objective: To assess the content validity of quality-of-life candidate instruments for atopic eczema in infants, children and adults in order to aid the decision on what instrument to include in the core outcome set for the quality-of-life domain., Methods: Six group discussions were conducted at the HOME VII Meeting in Tokyo. Each group was composed of 8-12 patients or parents of patients, clinicians, methodologists and pharmaceutical industry delegates and discussed one or two candidate instruments. The COSMIN criteria on relevance, comprehensiveness and comprehensibility were used to determine the overall content validity rating per instrument., Results: Content validity of the Infant's Dermatitis Quality of Life Index, Children's Dermatology Life Quality Index and the Childhood Atopic Dermatitis Impact Scale (CADIS) long-form was rated as sufficient (+). Results for the CADIS short-form, DLQI and Skindex were inconsistent (±). DISABKIDS, Infants and Toddlers Dermatology Quality of Life and ABS-A were classified as having insufficient content validity., Conclusions: The content validity rating allowed for a comparison of all candidate instruments and informed the consensus-seeking process regarding the core instrument for the quality-of-life domain., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Nuss procedure for pediatric patients with pectus excavatum has been practiced worldwide, including in Japan, due to the simple procedure and has a high therapeutic effect. Because it is usually performed under thoracoscopy to secure the safety, it is performed not only by pediatric or plastic surgeons but also by general thoracic surgeons. On the other hand, a risk of infection must always be considered in this method in which a foreign metal bar is used. In particular, when the skin barrier mechanism is declining due to skin diseases such as atopic dermatitis, the risk of infection of the implant may increase. The present case was an 8-year-old male with a history of atopic dermatitis. He underwent thoracoscopic Nuss procedure. Although there was no problem during his hospitalization, the bar was exposed from the skin on the 58th postoperative day with the infection triggered, and the unexpected early bar removal was performed on the 66th postoperative day. We report this case with some literature review.

Purpose: Although various risk factors for surgical site infection after anterior cruciate ligament reconstruction (ACLR) have been reported, the number of studies with large sample sizes on this topic is limited. The aim of the present study was to clarify the risk factors for early surgical site infection after ACLR in a large cohort using a national database in Japan., Methods: The data of patients who underwent ACLR from 2010 to 2015 were obtained from the Diagnosis Procedure Combination database, which covers approximately half of all hospital admissions in Japan. The outcome measures were the prevalences of surgical site infection and deep surgical site infection after ACLR during hospitalization. The association between the occurrence of surgical site infection and patients' demographic data, including sex, age, body mass index (BMI), smoking status, preoperative steroid use, and comorbidities such as diabetes, hepatic dysfunction, renal dysfunction, and atopic dermatitis, were examined using a multivariable logistic regression model., Results: Among 30,536 patients who underwent ACLR, 288 patients with surgical site infection (0.94%) and 86 with deep surgical site infection (0.28%) were identified. The univariate analysis showed that higher prevalences of surgical site infection and deep surgical site infection were associated with male sex, a higher BMI, atopic dermatitis, and preoperative steroid use. Patients with diabetes or hepatic dysfunction had a significantly higher prevalence of surgical site infection. The multivariable analysis showed that surgical site infection was significantly associated with male sex vs. female sex; odds ratio (OR), 2.90; 95% confidence interval (CI), 2.17-3.89, age of ≤ 19 vs. 20-29 years; OR, 1.56; 95% CI 1.13-2.15, BMI of ≥ 30.0 vs. 18.5-22.9 kg/m 2 ; OR, 1.72; 95% CI 1.16-2.54, diabetes (OR, 2.70; 95% CI 1.28-5.71), atopic dermatitis (OR, 7.19; 95% CI 2.94-17.57), and preoperative steroid use (OR, 6.18; 95% CI 2.32-16.52)., Conclusion: Atopic dermatitis, preoperative steroid use, young age (≤ 19 years), obesity (BMI of ≥ 30.0 kg/m 2 ), male sex, and diabetes were independent demographic risk factors for surgical site infection after ACLR. The present study will be useful when surgeons evaluate the risk of SSI after ACLR in terms of demographic aspects., Level of Evidence: III.

The potential allergenic proteins in beef were investigated. The sera of ten beef-allergic patients suffering from atopic dermatitis and having a positive RAST score to beef, aged 3-18 years, were obtained from Yoshida Hospital in Japan, and five non-allergic individuals were subjected to this study. The sera of the ten patients reacted strongly to a beef extract, but not to pork and chicken extracts by both ELISA and immunoblotting. The sera of the five control subjects did not react to any of these meat extracts. Three bands having molecular masses of approximately 200 kDa, approximately 67 kDa and approximately 60 kDa were observed by immunoblotting after SDS-PAGE. Two fractions of the beef extract from a Sephadex-gel (G-200) filtration column strongly reacted with the sera of the beef-allergic patients by ELISA and immunoblotting: one fraction had the approximately 67 kDa component and the other had the approximately 200 kDa and approximately 60 kDa components. One of them (approximately 67 kDa) was confirmed to be bovine serum albumin (BSA) by an analysis of the N-terminal amino acid sequence. We could not identify the others by sequencing, but the approximately 200 kDa and approximately 60 kDa components were presumed to be glycoproteins. Bovine gamma (BGG:globulin M.W. approximately 160 kDa) is a glycoprotein and has several subunits. The beef-allergic patients showed strong reactivity to the approximately 200 kDa and approximately 60 kDa components of pure BGG by immunoblotting. Inhibition-ELISA showed that pure BGG preparations strongly inhibited the binding of sera from the beef-allergic patients to the beef extract. These results suggest that the approximately 200 kDa, approximately 67 kDa and approximately 60 kDa components in the beef extract had strong allergenicity: approximately 67 kDa was BSA, and approximately 200 kDa and approximately 60 kDa were presumably aggregated BGG and it's heavy chain, respectively.