Pediatric frequent relapsing nephrotic syndrome with multiple cerebral infarctions accompanied by patent foramen ovale and cerebral venous sinus thrombosis: a case report.

BACKGROUND: Idiopathic nephrotic syndrome (NS) presents as a hypercoagulable state, of which thromboembolism (TE) is a well-known life-threatening complication. Although TE is more likely to occur in venous vessels than arterial vessels, arterial TE is important because it may cause after-effects, including tissue necrosis and cerebral infarction (CI); therefore, prompt diagnosis and appropriate treatment are required. We report a pediatric NS case with multiple CIs. CASE PRESENTATION: A 14-year-7-month-old Japanese girl was diagnosed with frequent relapsing NS, accompanied by headache and disturbance of consciousness during the second relapse. Brain magnetic resonance imaging (MRI) and four-dimensional computed tomography revealed multiple CIs, vasogenic edema, and cerebral venous sinus thrombosis (CVST). The patient had no underlying thrombophilia other than hypercoagulability due to NS and prednisolone (PSL), and no cardiac arrhythmia; however, a right-to-left shunt through the patent foramen ovale (PFO) was observed with the Valsalva maneuver by echocardiography. Therefore, we assumed that a potential cause of multiple CIs might be an embolic stroke, caused by thrombosis formed from a hypercoagulable state due to NS and PSL treatment and reached through PFO. Antiplatelet and anticoagulant therapies were administered for TE. She was treated with PSL and mycophenolate mofetil (MMF) for NS. Rituximab (RTX) was administered to prevent NS relapse after complete remission (CR). She underwent transcatheter PFO closure at age 14 years and 9 months because we considered that the right-to-left shunt through the PFO would be one of the risks for recurrent cerebral embolism when NS relapses. One year after the onset of CIs, an MRI indicated that the CVST had resolved, leaving no neurological sequelae due to CI; therefore, anticoagulant therapy was discontinued. And then she has been in CR for NS with only MMF therapy. CONCLUSIONS: CI is a serious complication in patients with NS. The pathogenesis of multiple CIs is various, including right-to-left shunt through PFO, in addition to the hypercoagulability due to NS. It is important to investigate and manage underlying risks such as PFO, besides preventing the relapses of NS by aggressive treatments using MMF and RTX, in patients with NS.

[RECOMMENDATION FOR ITCH ASSESSMENT FROM THE ATOPIC ITCH CONSENSUS MEETING (AICOM)].

BACKGROUND: Itch is the most troublesome symptom of atopic dermatitis, and it is important to assess it appropriately for optimal treatment. We discussed issues regarding itch and the most appropriate methods of assessment at the Atopic Itch Consensus Meeting (AICOM), attended by physicians and researchers with expertise in itch treatment and research. METHODS: The AICOM participants prepared a draft consensus statement that addressed the most appropriate itch assessment methods for age groups <2 years, 2-6 years, 7-14 years, and ≥15 years. Consensus was defined as agreement by ≥80% of the participants. RESULTS: Votes were cast by 20 participants (8 dermatologists, 7 pediatricians, and 5 researchers), and a consensus on the best current methods of itch assessment was reached with 95% agreement. For infants and preschool children, because subjective evaluation is difficult, a checklist for itch assessment was developed for caregivers. CONCLUSION: For itch assessment, we recommend subjective evaluation by the patient using a rating scale. For infants and preschoolers, evaluation should be done by the caregiver using a checklist, combined with objective evaluation (of skin lesions, for example) by a physician. We anticipate that more objective itch assessment indices will be established in the future.

Factors associated with positive mental health in Japanese young adults with a history of chronic diseases during childhood: A qualitative study.

PURPOSE: Factors associated with positive mental health in children with chronic diseases remain unclear. Supporting the development of positive mental health in children with chronic diseases can enhance their mental health throughout childhood and adulthood. This study aimed to identify the factors associated with positive mental health among Japanese young adults with a history of chronic pediatric diseases. DESIGN AND METHODS: Participants aged 18-25 years, with a history of chronic pediatric diseases, were recruited from a population of students at a university. Semi-structured interviews were conducted. The data were analyzed using thematic analysis. After the initial coding of each transcript, the researchers discussed and identified a set of main themes, categories, and subcategories. RESULTS: Ten participants aged 19-22 years were interviewed. Their chronic diseases were diverse and included childhood cancers and allergic diseases. Seven themes (proactive coping, positive coping, negative coping, eudaimonia, hedonia, independence, and awareness) emerged from 21 categories and 70 subcategories identified. A thematic map was applied to two domains (protective factors and well-being factors) and to three inter-related constructs (individual, family, and community/society). CONCLUSIONS: The findings indicated that within the well-being factors, meaning in life was prominent, and within the protective factors, stress coping was found to facilitate positive mental health among individuals with a history of chronic pediatric diseases. PRACTICE IMPLICATIONS: In children with chronic diseases, support for finding appropriate coping strategies that enhance their optimism and symbiotic relationships in the community/society are important, including valuing little things in their lives, such as play and learning.

A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations.

Background: Allergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed. Objective: We sought to detect genetic variants associated with differences in immune responsiveness against allergen components. Methods: The participants of the present study were recruited from the Tokyo Children's Health, Illness, and Development study, and allergen component-specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16). Results: We performed GWAS on 564 participants of the Tokyo Children's Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10-8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10-8). Conclusions: Our data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.

Lymphocyte stimulation test for diagnosing hen's egg yolk-induced enterocolitis syndrome.

Background: There is currently little research into factors predicting the results of an initial diagnostic oral food challenge (OFC) test for food protein-induced enterocolitis syndrome (FPIES). Objective: The present study aimed to identify predictors of the diagnosis of hen's egg yolk-induced FPIES (HEY-FPIES). Methods: The present monocentric study was performed at Tokyo Metropolitan Children's Medical Center and included patients who underwent hen's egg yolk OFC (HEY-OFC) between March 2018 and March 2023 to assess for HEY-FPIES. The baseline characteristics of the groups and HEY-OFC positivity or negativity were then compared. Univariate analysis was conducted by using the Mann-Whitney U test or Fisher exact test. Receiver operator characteristic analysis was used to create probability curves. Results: In total, 35 patients were analyzed; of these, 17 were HEY-OFC-positive. No significant difference was observed between the HEY-OFC-positive and HEY-OFC-negative groups in terms of background factors except for the HEY-LST value, which was significantly higher in the HEY-LST group (P = .027). Receiver operator characteristic analysis demonstrated that the area under the curve for HEY-OFC positivity using the HEY-LST value was 0.719 (95% CI = 0.541-0.897). The statistically optimal cutoff value for the HEY-LST was 610%, which had a clinical sensitivity and specificity of 64.7% and 83.3%, respectively. Conclusions: The present study demonstrated that the HEY-LST may be a useful predictor of the result of an initial OFC for HEY-FPIES.

Risk factors of admission in school children with severe atopic dermatitis.

There are no data about risk factor of admission and long-term (>1 year) prognosis of proactive therapy using topical corticosteroids (TCSs) in school children. This study aims to identify the prognosis of school children over 3 years treated with proactive therapy after hospitalization due to atopic dermatitis (AD). This retrospective cohort study used electronic medical record data of schoolchildren (aged 5-19 years) with a long-term admission program for AD at the National Center for Child Health and Development from January 2008 to December 2013. Long-term prognosis at 1 and 3 years after discharge were retrospectively identified from their medical records. The most common exacerbation factor was poor adherence (51.8%). At 1 and 3 years after hospitalization, 87.3% and 74.3%, respectively, of the children used TCSs on their trunk and limbs less than twice a week. Investigator's Global Assessment of AD scores were ≤1 for 81.0%and 75.7% at 1 and 3 years after discharge, respectively. AD was well-controlled during follow-up. Rehospitalization due to AD was observed in 11.8% children. Poor adherence was biggest risk factor for admission. Children with severe AD could achieve well-controlled AD with a long-term admission AD program and home-based proactive therapy using TCSs for 3 years after discharge. Maintaining good adherence for AD treatment is required to prevent exacerbation and improve future prognosis in school children. However, we need to engage for the children who required rehospitalization.

Executive summary: Japanese guidelines for atopic dermatitis (ADGL) 2021.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

English Version of Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021.

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Development and Feasibility of a Mobile Asthma App for Children and Their Caregivers: Mixed Methods Study.

BACKGROUND: Mobile health apps can support the self-management of pediatric asthma. Previous studies on mobile apps for children aged >7 years with asthma are limited, and most reports on asthma apps do not consider interactions between the children and their caregivers. Therefore, we developed an asthma app for children aged 0-12 years and their caregivers based on the results of our previous study regarding user needs. OBJECTIVE: The aim of this study was to evaluate the feasibility of a developed mobile app for children with asthma and their caregivers and to modify and complete the app according to the feasibility results. METHODS: We recruited children diagnosed with persistent asthma by an allergy specialist at 2 children's hospitals, 1 university hospital, 2 general hospitals, and 1 pediatric clinic. Thereafter, the app usage was assessed, and questionnaires were administered. This study used convergent mixed methods, including providing user feedback about the pediatric asthma app, completing questionnaire surveys regarding preferences, and obtaining quantitative data about app usage. Quantitative data were analyzed based on the ratings provided for the app features used by the participants, and the usage of the app features was analyzed using descriptive statistics. Qualitative data were analyzed via a descriptive qualitative research analysis and were used to identify codes from the content-characteristic words. RESULTS: In total, 30 pairs of children aged 2-12 years and their caregivers responded to the 3-month survey, and 20 pairs of children aged 4-12 years and their caregivers responded to the 6-month survey. In the 3- and 6-month surveys, "record" was the most commonly used feature by both caregivers and children. The average access logs per month among the 20 pairs ranged from 50 to 79 in the 6-month survey. The number of access logs decreased over time. In the qualitative results, app utilization difficulties were identified for 6 categories: record, preparing, alert settings, change settings, mobile phone owner, and display and motivation. Regarding app feasibility, 60% (12/20) of the caregivers strongly agreed or agreed for all evaluation items, while 63% (7/11) of the children strongly agreed or agreed for 6 items, excluding satisfaction. In the qualitative results, feasibility evaluation of the app was classified into 3 categories: high feasibility of the app, improvement points for the app, and personal factors preventing app utilization. Based on the results of the feasibility analysis, the final version of the app was modified and completed. CONCLUSIONS: The app feasibility among children with asthma and their caregivers was generally good. Children aged 7-12 years used elements such as record, quiz, and manga. This app can support the continuous self-management of pediatric asthma. However, efforts must be taken to maintain and improve the app quality. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000039058; https://tinyurl.com/3na9zyf8.

Food Protein-induced Enterocolitis Syndrome Due to Rice in a Japanese Infant: A Case Report.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergy characterized by repetitive vomiting within 1-4 h and/or diarrhea within 24 h after ingesting the causative food. We herein report a rare Japanese case of rice-induced FPIES. A six-month-old, female, Japanese patient presented to the emergency room (ER) with the complaint of vomiting after feeding. Postprandial vomiting had occurred occasionally since she started ingesting solid food at the age of 5 months. Rice-induced FPIES was suspected only after the fourth ER visit based on the characteristic history of recurrent vomiting occurring 1-2 h after ingesting food containing rice. Allergen-specific IgE testing and a skin prick test with an allergen scratch extract were both negative for rice. During an oral food challenge test (OFC), vomiting was observed after the patient ingested 2 g of rice porridge. Based on the OFC results and the entire clinical course, FPIES due to rice was diagnosed. A lymphocyte stimulation test with rice revealed a significantly elevated stimulation index. Rice-induced FPIES is rarely reported among Japanese infants despite rice being a staple in the Japanese diet. The prevalence of rice-induced FPIES differs greatly among populations, suggesting a multifactorial cause associated with its development. Delays in diagnosis are common in FPIES, and our case demonstrates the importance of obtaining a dietary history of food ingested prior to symptom onset in cases of infantile repetitive vomiting.

Food-Induced Anaphylaxis among Children Weighing <15 kg: A Single-Center Case Series of the Pediatric Emergency Department.

INTRODUCTION: Food-induced anaphylaxis among infants shows an increasing prevalence; however, the prescription of epinephrine auto-injectors (EAIs) for children weighing <15 kg is associated with issues of the needle length and the epinephrine dose. Several studies have shown age-related differences in food-induced anaphylaxis, although little is known about the weight-related differences in food-induced anaphylaxis. This study aimed to reveal the incidence, clinical characteristics, and management of food-induced anaphylaxis in children weighing <15 kg. METHODS: This chart review included children who visited the pediatric emergency department (ED) of the National Center for Child Health and Development (Tokyo, Japan) from January 2014 to December 2016 and were diagnosed with food-induced anaphylaxis. The severity of anaphylaxis was evaluated using the Sampson Grading Scale. RESULTS: Of 89,232 ED visits, 444 visits included patients with food-induced anaphylaxis, after excluding cases of food-induced anaphylaxis related to oral desensitization therapy. The incidence was 4.98 per 1,000 visits. More than half of the children (n = 247/444, 55.6%) weighed <15 kg. The proportion of grade 3 and higher severity anaphylactic symptoms was 74.5% (184/247) in children weighing <15 kg and 79.2% (156/197) in children weighing 15 kg or more. The recurrence rate of food-induced anaphylaxis was 22.3% (55/247) in children weighing <15 kg and 48.7% (96/197) in children weighing 15 kg or more. Among the children weighing <15 kg, the proportion of those with recurrent food-induced anaphylaxis was 4 times higher in children weighing 10-15 kg than in those weighing <10 kg (32.2% [47/146] vs. 7.9% [8/101]). The proportion of patients who were prescribed EAIs before each visit was 25.5% (14/55) in children weighing <15 kg with a history of food-induced anaphylaxis. CONCLUSION: Food-induced anaphylaxis among children weighing <15 kg occurred as frequently and was as severe as that among children weighing 15 kg or more. However, the proportion of patients prescribed EAIs was very low in children weighing <15 kg with food-induced anaphylaxis. The potential need for EAIs is suggested among children weighing <15 kg, especially among children weighing 10 kg or more but <15 kg.