Continuous cow's milk protein ingestion during infancy may promote casein-specific IgG4 production.

Background: Early supplementation and subsequent discontinuation of cow's milk formula (CMF) may increase the risk of cow's milk allergy in breast-fed infants, but little is known about the relationship between continuous CMF ingestion and cow's milk protein-specific immunoglobulin production. Objective: This study aimed to clarify the aforesaid relationship in cow's milk-sensitized infants. Methods: Using data from a randomized controlled trial of a Japanese birth cohort, we performed a subgroup analysis of participants who had ingested CMF in the first 3 days of life and exhibited a positive skin prick test response to cow's milk at age 6 months. We compared the differences in median titers of cow's milk-specific IgE, casein-specific IgE, and casein-specific IgG4 levels between participants who continued daily or intermittent CMF ingestion up to age 6 months (the "continuous group") and participants who discontinued CMF ingestion before age 6 months (the "discontinued group"). Results: From among 462 trial participants, 49 (10.6%) were included in this study (21 in the continuous group and 29 in the discontinued group). The median titer of cow's milk-specific IgE was 0.17 kUA/L (interquartile range [IQR] = <0.10 to 0.57) in the continuous group and 0.66 kUA/L (IQR = 0.49-1.18) in the discontinued group (P = .0008). The median titer of casein-specific IgE was <0.10 kUA/L (IQR = <0.10 to 0.15) in the continuous group and <0.10 kUA/L (IQR = <0.10 to 0.37) in the discontinued group (P = .51). The median titer of casein-specific IgG4 was 2.58 mgA/L (IQR = 0.77-6.73) in the continuous group and 0.09 mgA/L (IQR = 0.07-0.13) in the discontinued group (P < .0001). Conclusion: Continuous CMF ingestion may promote casein-specific IgG4 production in cow's milk-sensitized infants.

A case of white bean allergy.

White bean allergy is uncommon and rarely reported. Herein, we report a case of white bean allergy in a patient with Down syndrome. A 7-year-old girl with Down syndrome experienced allergic symptoms twice after eating white bean and visited our hospital for a food allergy investigation. An ImmunoCAP assay revealed a white bean-specific IgE (13.4 kUA/L) in the patient's serum. In addition, her skin prick test result was positive. Moreover, ingestion of 2 g of boiled white beans in an oral food challenge test induced intermittent cough, desaturation, generalized urticaria, abnormal sleep, and mild hypotension. Thus, we diagnosed the patient with white bean allergy. We performed western blotting and mass spectrometric analysis and detected the following allergens: Phytohemagglutinin, group 3 late embryogenesis abundant protein, lipoxygenase, and legumin. In addition, we detected several candidate allergenic proteins for the first time. White bean, runner bean, or azuki bean was considered the primary source of sensitization because although immunoblotting inhibition tests revealed that the abovementioned beans inhibited other legumes, soybean, which she tolerates, showed little inhibition of the other legumes. However, we could not confirm whether the patient could ingest legumes other than soybean or white bean because her family did not wish to continue with further testing. This is the first report of a case of systemic allergic reactions to white bean in a child with Down syndrome. Further studies are needed to identify white bean allergens and understand the relationship between Down syndrome and white bean allergy.

Jug r 1 sensitization in 0- to 35-month-old children with egg, milk, or wheat sensitization.

Background: The incidence of tree nut allergies in children is increasing, with walnut allergy being the most common in the United States and Japan. Allergic reactions, including anaphylaxis, frequently occur at the first intake of tree nuts, suggesting prior sensitization. Objective: Our aim was to identify which children should be considered for workup for preexisting sensitization. Methods: Juglans regia (Jug r) 1-specific IgE screening for 0- to 35-month-old children who had a positive specific IgE result for egg white, milk, or wheat and had never ingested walnuts was conducted at a food allergy referral hospital between November 2018 and December 2022. Clinical data regarding age; sex; allergic disease complications; and egg, milk, or wheat allergy were examined retrospectively. Results: The rate of Jug r 1-specific IgE positivity (level > 0.34 kUA/L) of 205 children (125 of whom were boys) was 9.8%, with a median Jug r 1-specific IgE level of 12.5 kUA/L in patients with a positive test result. Eczema was observed in 119 patients (58%). The rate of Jug r 1-specific IgE positivity was significantly higher in the eczema-positive group (15.1% [18 of 119]) than in the eczema-negative group (2.3% [2 of 86]) (P = .002). In the eczema-positive group, the rates of Jug r 1-specific IgE positivity per sensitized antigen were 13.7% for egg, 17.0% for milk, and 17.1% for wheat. The rate of Jug r 1-specific IgE positivity was significantly higher in the group with severe eczema (26.6% [17 of 64]) than in the group with nonsevere eczema (1.8% [1 of 55]) (P < .001). Conclusion: Even in children younger than 3 years, 15% of children with eczema and egg, milk, or wheat sensitization were sensitized to Jug r 1.

Cross-cultural adaptation of the pain understanding and confidence questionnaire into Japanese.

[Purpose] This study aimed to develop a culturally adapted Japanese version of the Pain Understanding and Confidence Questionnaire (PUnCQ). The first-factor structure describes management from 12 perspectives for a case vignette of chronic pain and determines whether the management is based on a biomedical or biopsychosocial perspective. The second-factor structure evaluates the confidence level in management skills for the same case from 21 perspectives. [Participants and Methods] We conducted a cross-cultural adaptation based on five stages according to Beaton's guidelines (two forward translations, creation of an integrated forward translation version, two backward translations, creation of a provisional Japanese version, and a pilot test). In the pilot test, we asked 40 Japanese physical therapists to rate their understanding of the PUnCQ descriptions on a five-point Likert scale (1, not at all understandable; 5, completely understandable) and provide comments when they rated 1 to 3. We repeated revisions and pilot tests until less than 10% of the respondents rated 1 for all descriptions. [Results] By conducting two rounds of the pilot test, all items of descriptions satisfied the preestablished criteria. [Conclusion] A Japanese version of the PUnCQ was developed.

Kestose Increases the Relative Abundance of Faecalibacterium spp. and Nominally Increases Cow Milk Tolerant Dose in Children with Cow's Milk Allergy - Preliminary Results.

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.

Risk factors for intolerance of oral 5-aminosalicylic acid preparations in pediatric ulcerative colitis.

BACKGROUND: No previous study of Japanese children with ulcerative colitis (UC) has reported the risk factors for intolerance of 5-aminosalicylic acid (5-ASA). We aimed to identify risk factors for intolerance of oral 5-ASA preparations in pediatric UC. METHODS: Patients with childhood-onset UC who were seen at our hospital between November 2003 and March 2020 were investigated. Intolerance of 5-ASA was defined as having clinical symptoms (pyrexia, abdominal pain, diarrhea, bloody stool) that worsened after starting oral administration of 5-ASA and improved after discontinuation of 5-ASA. Patient sex, age, body size, laboratory data, pediatric UC activity index scores, and colonoscopy-based determinations of the extent and severity of the affected lesion at initiation of 5-ASA of intolerant and tolerant groups were compared. RESULTS: Fifteen patients were in the intolerant group, and 37 were in the tolerant group. The leukocyte count, C-reactive protein level, and erythrocyte sedimentation rate were significantly higher in the intolerant group than the tolerant group; the albumin level in the intolerant group was significantly lower. All intolerant patients and 68% of tolerant patients had pancolitis (Paris classification E4). Patients with a large, affected area (Paris classifications E3 and E4) more frequently had intolerance to 5-ASA than patients with a small lesion. The cumulative Mayo endoscopic subscore (cMES), which is the sum of MES scores for six regions of the large intestine, was significantly higher in the intolerant group. CONCLUSIONS: Pediatric UC patients with more intense inflammation and a large lesion could have an increased risk of intolerance for 5-ASA.

Exercise-Induced Allergic Reactions in Children Desensitized to Hen's Eggs and Cow's Milk by Oral Immunotherapy.

BACKGROUND: Exercise-induced allergic reactions on desensitization (EIARDs) after successful in-hospital rush oral immunotherapy (OIT) for wheat allergy have been reported. However, the incidence rates of EIARDs after rush OIT for egg allergy and milk allergy have not been determined. OBJECTIVE: To determine the frequency of EIARDs and risk factors associated with rush OIT for egg and milk allergy. METHODS: This retrospective chart review, conducted in January 2020, enrolled 64 and 43 patients who underwent rush OIT for egg and milk allergy, respectively (in 2010 to 2014). In particular, 48 and 32 desensitized patients underwent exercise-provocation tests (Ex-P) after allergen administration (4,400 mg boiled egg white and 6,600 mg cow's milk protein, respectively). The EIARDs were determined by Ex-P or a suspicious event even after passing the Ex-P. Specific IgE levels to egg white, cow's milk, ovomucoid, casein, α-lactalbumin, and ß-lactoglobulin were analyzed using ImmunoCAP. RESULTS: At least one episode of EIARD was observed in 10 and 17 patients with egg and milk allergy (21% and 53%), respectively, which persisted for more than 5 years in one patient with egg allergy (2.1%) and 11 patients with milk allergy (34.4%) as of January 2020. We could not find background differences between the EIARD-positive and EIARD-negative groups, except that the egg white-specific IgE/total IgE ratio before rush OIT was significantly higher in patients with egg allergy with EIARD than in those without it. CONCLUSIONS: Exercise-induced allergic reactions on desensitization were more frequent and common in patients with milk allergy. Moreover, EIARDs to milk allergy were more likely to persist than those to egg allergy.

Clinical risk factors at 3 months of age for the development of bronchial asthma at 36 months of age.

BACKGROUND: We examined the associations between factors evident at the routine 3-month well-child visit (WCV) and the risk of developing 36-month parent-reported physician-diagnosed bronchial asthma (BA). METHODS: This longitudinal study was conducted in Nagoya City, Japan, and included 40,242 children who qualified for the 3-month WCVs in the city between April 1, 2016 and March 31, 2018. In total, 22,052 (54.8%) questionnaires linked to their 36-month WCVs were analyzed. RESULTS: The prevalence of BA was 4.5%. The multivariable Poisson regression model identified male sex (adjusted risk ratio [aRR], 1.59; 95% confidence interval [CI]: 1.40-1.81), born in autumn (aRR, 1.30; 95% CI: 1.09-1.55), having at least one sibling (aRR, 1.31; 95% CI: 1.15-1.49), wheeze history before 3-month WCVs, with clinic/hospital visit: aRR, 1.99; 95% CI: 1.53-2.56; hospitalization: aRR, 2.99; 95% CI: 2.09-4.12, eczema with itch (aRR, 1.51; 95% CI: 1.27-1.80), paternal history of BA (aRR, 1.98; 95% CI: 1.66-2.34), maternal history of BA (aRR, 2.11; 95% CI: 1.77-2.49), and rearing pets with fur (aRR, 1.35; 95% CI: 1.15-1.58) were independent risk factors for BA at 36 months of age. The combination of severe wheeze history (with clinic/hospital visit or hospitalization) and maternal and paternal BA could identify high-risk infants whose prevalence of BA was 20%. CONCLUSIONS: The combined assessment of important clinical factors enabled us to identify high-risk infants set to derive optimal benefit from health guidance provided to the parent or caregiver of the child or infant at WCVs.

Evaluation of peripheral basophil activation during exercise provocation test for desensitized patients.

Some food allergic patients who have undergone oral immunotherapy develop exercise-induced allergic reactions on desensitization (EIARDs). This study investigated basophil activation status during the exercise provocation test (EPT) performed to diagnose EIARD. EPT was performed on 20 participants, and in vivo basophil activation status was analyzed using activation markers CD203c and CD63. The results showed that there was no significant difference between EPT-positive and negative subjects for basophil activation status throughout EPT. Consequently, in vivo basophil activation after ingestion of the causative food may not be associated with EIARDs. New tests are desired for predicting EIARDs.

Effects of regular soy formula intake between 1 and 2 months of age on food sensitization in infancy.

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.

[COMPARISON OF WHEAL SIZE INDUCED BY BIFURCATED NEEDLE® AND SMARTPRACTICE® PRICK LANCET].

BACKGROUND: There is reportedly a difference in the diameter of the skin reaction induced by different types of skin prick test (SPT) devices. We compared the SPT diagnostic accuracy and wheal size between a Bifurcated Needle® (BN) and SmartPractice® Prick Lancet (PL), which are commercially available in Japan. METHODS: An SPT was performed on 15 adults with and 10 without subjective symptoms of cedar pollinosis who wished to be examined for Japanese cedar pollen (JCP) sensitization. The SPT was performed blindly with a BN or PL with 10mg/ml of histamine dihydrochloride, 50% glycerosaline control, and JCP extract solution (TORII PHARMACEUTICAL CO., LTD., Tokyo, Japan). The wheal sizes induced by the BN and PL were then compared. The JCP-specific IgE antibody titer was measured to compare the sensitivity and specificity of the SPT. RESULTS: Histamine wheal diameters were 6.0 (5.5-6.5) mm by BN and 6.0 (5.5-6.5) mm by PL (p=0.67), and none of the negative control solutions induced wheal. The respective sensitivity and specificity for cedar sensitization were 100% and 86% for BN, 100% and 79% for PL, and the areas under the ROC curve were 0.72 and 0.69 (p=0.32). CONCLUSION: The diagnostic accuracy of cedar pollen extract based on specific IgE-JCP sensitization and the diameter of the wheal produced by a BN and PL were considered equivalent.

The clinical cross-reactivity and immunological cross-antigenicity of wheat and barley.

BACKGROUND: Some patients with wheat allergy have been reported to show clinical cross-reactivity to barley. However, it is not clear whether the development of barley allergy in patients with wheat allergy is due to cross-antigenicity between wheat and barley. This study aimed to determine the clinical cross-reactivity and immunological cross-antigenicity of wheat and barley. METHODS: The results of barley oral food challenges (OFCs) were compared before and after oral immunotherapy (OIT) for wheat in nine patients with wheat allergy to estimate the clinical cross-reactivity of wheat and barley. Moreover, we performed enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblotting inhibition using serum from seven patients allergic to wheat and barley. RESULTS: Nine patients who had positive barley-OFC results performed before OIT for wheat were all negative on barley-OFC performed after OIT. In ELISA inhibition, preincubation of serum from patients allergic to wheat and barley with a high barley extract concentration inhibited binding of IgE to wheat extract by less than 10%. On the other hand, wheat and barley extracts equally inhibited binding to barley sIgE at high concentrations. In the immunoblotting inhibition test, the spots of wheat were inhibited but weakly by barley extracts, and most of the spots of barley were inhibited even by low concentrations of the wheat and barley extract. CONCLUSIONS: We showed that barley allergy associated with wheat allergy is caused by cross-reactivity from wheat. The OIT for wheat is one of the promising options for barley allergy.

Mealtime Regularity Is Associated with Dietary Balance among Preschool Children in Japan-A Study of Lifestyle Changes during the COVID-19 Pandemic.

The novel coronavirus-19 (COVID-19) pandemic has considerably impacted children's lives. The aim of this study was to determine whether the pandemic affected mealtime regularity among preschool children and whether maintaining regular mealtimes or changes in mealtime regularity during the pandemic were related to dietary balance, including chronological relationships. This online cross-sectional survey involving individuals registered with a company that provides meals to children aged 2-6 years was conducted in February 2021. Using a 40-point scale, a healthy diet score (HDS) was developed to evaluate children's dietary balance. The participants were divided into four groups based on their responses, and multiple regression analyses were performed with the HDS as the dependent variable. Maintaining regular mealtimes was associated with practices such as waking and going to bed earlier, less snacking, and eating breakfast every day. Even after adjusting for basic attributes, lifestyle habits, household circumstances, and other factors, regular mealtimes were still positively correlated with the HDS. These findings indicate that maintaining regular mealtimes is associated with higher HDS scores and better lifestyle habits. Furthermore, as the changed HDS was higher in the group whose mealtimes became regular during the pandemic, adopting regular mealtimes may lead to a more balanced diet.

Prevalence of infantile wheezing and eczema in a metropolitan city in Japan: A complete census survey.

Infantile wheezing and eczema are associated with the subsequent onset of asthma and other atopic diseases. However, there are no large population-based surveys on infantile allergic symptoms in Japan. The objective of the study was to determine the prevalence of wheezing and asthma in infants in Nagoya, Japan. This population-based cross-sectional study was performed in the metropolitan city of Nagoya, Japan. We surveyed parents to ascertain the prevalence of wheezing and eczema in infants who attended group health checkups at 3, 18, and 36 months of age. Their parents completed modified questionnaires from the International Study of Asthma and Allergies in Childhood. More than 90% of the approximately 40,000 children in each study group living in the target area were included in the survey. The prevalence of wheezing was 8%, 17%, and 13% at 3, 18, and 36 months, respectively, and was characterized by birth season. The prevalence of eczema was 24%, 30%, and 31%, at 3, 18, and 36 months, respectively. Participants born in autumn and winter had a higher incidence of eczema in each age group. Three-quarters of the children had a parental history of allergic conditions. Parental allergic diseases and male gender are risk factors for wheezing and eczema in children. This survey had a high response rate and covered almost the entire population of the target age groups in a large city. We believe that the results of this study, therefore, provide a much higher level of confidence regarding the prevalence of allergies in infants in Japan than that in previous studies with limited cohorts.

Biomechanical assessment of the first dorsal compartment of the wrist: A fresh cadaver study with relevance to de Quervain's disease.

Resistance of de Quervain's disease to conservative treatment has been associated with an intertendinous septum in the first compartment. This study aimed to investigate the relationship between intertendinous septum's presence or absence, internal pressure and wrist positon in the first compartment. Fourteen arms were obtained from seven fresh frozen cadavers. A pressure sensor was inserted into the first compartment; if a septum was present, the pressure sensor was inserted into the abductor pollicis longus (APL) side and the extensor pollicis brevis (EPB) side, respectively. Three wrist positions were also tested: neutral, 45° flexion, and 45° extension. Intertendinous septa were present in seven wrists. The average pressure change in the first compartment measured on the EPB side of a present septum was significantly greater than that measured on the APL side of a present septum or where no septum existed: no septum = 54.6 ± 48.3 kPa; septum, EPB = 81.7 ± 76.5 kPa; and septum, APL = 32.8 ± 37.4 kPa. The average pressure change was also significantly greater in the flexion wrist position relative to the neutral and extension positions: neutral = 36.3 ± 58.0 kPa; 45° flexion = 79.5 ± 65.9 kPa; and 45° extension = 50.4 ± 42.6 kPa. Clear relationships existed between (1) the presence of a septum and increased internal pressure on the EPB side in the first compartment and (2) increased internal pressure with the wrist at 45° flexion compared with the neutral and extension position.

Effects of delivery mode and labor duration on the development of food sensitization in infancy.

BACKGROUND: The effects of delivery mode and labor duration on the development of food sensitization (FS) in infancy remain unclear. OBJECTIVE: To elucidate the potential effects of delivery mode and labor duration on FS development by 6 months of age. METHODS: Using data from a randomized controlled trial of a birth cohort from 4 Japanese hospitals that assessed cow's milk allergy development by 6 months of age, we performed a nested case-control trial of 462 participants who had undergone the final assessment at 6 months of age. FS was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, or soy. For the primary outcome, we calculated the adjusted odds ratio of vaginal delivery (VD) relative to cesarean delivery for FS development by 6 months of age using a multivariable logistic regression analysis. For the secondary outcome, we compared labor durations between participants with and without FS using the Mann-Whitney U test. RESULTS: The adjusted odds ratio of VD for FS development was 2.54 (95% confidence interval, 1.32-4.87; P = .005). The median labor duration was significantly longer in participants with FS (5.7 hours, interquartile range, 2.7-10.1) than in participants without FS (4.5 hours, 1.1-8.2) (P = .01). CONCLUSION: VD was considerably associated with an increased risk of FS in infancy, and longer labor durations may promote FS development.

Evaluation of the European League Against Rheumatism/American College of Rheumatology-2019 classification criteria in patients with childhood-onset systemic lupus erythematosus: a single-center retrospective study.

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren's syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population. Key Points • The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity. • The EULAR/ACR-2019 criteria more frequently misclassified non-SLE patients who did not have SLE, especially those with MCTD or pSS, as having SLE than the previous criteria in patients with childhood onset. • The weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be a more appropriate classification of SLE for a pediatric population.