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Introduction: Difamilast is the first selective phosphodiesterase 4 inhibitor approved for atopic dermatitis (AD) in Japan. A phase 3, 52-week, open-label study is ongoing to establish efficacy and safety of difamilast ointments in infants with AD aged 3 to < 24 months because a clinical study has not been conducted in this population. Methods: This study consisted of a 4-week primary evaluation period in which difamilast 0.3% ointment was applied twice daily to Japanese infants aged 3 to < 24 months (n = 41) and an ongoing 48-week long-term extension period in which difamilast 0.3% or 1% ointment was applied based on existing symptoms. The data on efficacy and safety of difamilast were obtained as of an interim report in the study period. Results: The response rate in Investigator's Global Assessment score was 45.0% at week 1, which was maintained at 56.1% at week 4 and 63.4% at the interim report. Infants achieved the response rate in Eczema Area and Severity Index 75 (improvement of ≥ 75%) of 47.5% at week 1, which further improved to 82.9% at week 4 and 78.1% at the interim report. Adverse events (AEs) were reported in 22 (53.7%) infants in the primary evaluation period: of those the most frequent AE was nasopharyngitis (19.5%) followed by dermatitis contact (7.3%). As of the interim report, 36 (87.8%) infants experienced AEs: of those, nasopharyngitis (70.7%) and gastroenteritis (22.0%) were most frequently observed. The total AEs were mostly mild or moderate in severity. No investigational medicinal product-related AEs and no AEs leading to discontinuation were reported. Conclusion: Difamilast ointments applied twice daily to Japanese infants with AD aged 3 to < 24 months is effective and well tolerated as of the interim report in the study period. The final results will be reported in the near future. Clinical Trial Registration: Clinical Trials. gov identifier: NCT05372653. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the association between atopic dermatitis in pregnant women and preterm births, accounting for maternal ritodrine hydrochloride administration status. Methods: Data of 83,796 women with singleton pregnancies at and after 22 weeks of gestation (enrolled between 2011 and 2014) were analyzed. These data were obtained from the Japan Environment and Children's Study. Atopic dermatitis was defined based on self-reported questionnaire responses obtained during the first trimester. The primary outcome measures were preterm births before 37, 32, and 28 weeks of gestation. Using a multivariable logistic regression model, odds ratios for preterm births in pregnant women with atopic dermatitis were calculated, with women without atopic dermatitis included in the reference group. This analysis considered confounding factors and maternal ritodrine hydrochloride administration. Results: Among pregnant women with atopic dermatitis, the adjusted odds ratios (95% confidence intervals) for preterm births before 37, 32, and 28 weeks of gestation were 0.89 (0.81–0.98), 0.98 (0.74–1.30), and 0.88 (0.50–1.55), respectively. This trend remained consistent after excluding participants who received ritodrine hydrochloride. Conclusions for practice: Atopic dermatitis in pregnant women was significantly associated with a decreased incidence of preterm births before 37 weeks of gestation, even after accounting for the effects of maternal ritodrine hydrochloride administration. Significance: What is already known on this subject?: Atopic dermatitis is among the most prevalent chronic dermatological conditions in pregnant women. The association between atopic dermatitis in pregnant women and obstetric outcomes remains unclear owing to conflicting research findings. What this study adds?: Atopic dermatitis in pregnant women was significantly associated with a decreased incidence of preterm births before 37 weeks of gestation. The trend was the same in participants without maternal ritodrine hydrochloride administration. [ABSTRACT FROM AUTHOR]

Background: The nature of itch sensation varies depending upon the patient and the disease. However, few studies have focused on verbal expressions describing itch of atopic dermatitis (AD) in quality. Objectives: To investigate itch quality in patients with AD compared with that of urticaria. Methods: We conducted an online questionnaire survey describing itch experiences in June 2021. Participants were Japanese patients who had visited hospitals for their consultations and treatments of AD or urticaria in the last 6 months, and 295 and 290 responses, respectively, to questions using 12 terms describing itch quality were analyzed. Results: The most suitable expression describing intense itch that patients could not help scratching differed between the diseases, where most AD patients selected "muzumuzu" (a mimetic word for creepy-crawly itch) (27%) or "painful itch" (20%), and most urticaria patients selected "muzumuzu" (24%) or "itch like mosquito bites" (22%). The most suitable expressions describing itch that would make patients happiest if improved was "painful itch" (27%) in AD patients, significantly higher than urticaria patients (19%). More AD patients (55%) responded that they sometimes felt itch even after the skin symptoms had subsided than urticaria patients (41%). The most suitable expression of remnant itch selected was "muzumuzu" for AD (58/161 patients, 36%) and urticaria (29/120 patients, 24%). Conclusion: The quality of itch sensations can be classified not only between diseases but also during the clinical course of each disease. Significant expressions that patients with AD use to describe itch sensations could promote more appropriate treatment for itch. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness. Objectives: We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis. Methods: In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase. Results: Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively. Conclusions: These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as a treatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg. [ABSTRACT FROM AUTHOR]

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts. SARS-CoV-2 infection has been linked to various persistent or new-onset health consequences, including disruption of the immune system. Here, the authors investigate the risk of new-onset allergic diseases following SARS-CoV-2 infection using data from South Korea, Japan, and the UK. [ABSTRACT FROM AUTHOR]

Data on the problems physicians face when providing care for atopic dermatitis (AD) is limited. To understand the current status of AD management in Japan and identify the difficulties physicians are having and their support requirements, a cross-sectional online survey was conducted using the AD task force of the Japanese Society for Cutaneous Immunology and Allergy. Society members were sent an online questionnaire on demographic information, daily clinical practice, and perceptions of AD management. Using responses to 17 items listed as barriers to the treatment of atopic dermatitis (Question 12) and questions about the treatment difficulty of those items, 284 respondents were divided into three groups using unstratified cluster analysis. These three groups were classified as highdifficulty, medium-difficulty, and low-difficulty groups, and the relationship between physicians' cognition and daily practice was examined for each group. There were no significant differences in affiliations or specializations among the three clusters. The low-difficulty group had a significantly higher proportion of participants believing that it was possible to achieve long-term remission, satisfaction, and motivation in AD management while carrying out precise assessments of skin lesions as part of their daily practice. Some physicians experience problems in their practice. This results indicate that AD management can be improved if satisfaction and motivation can be increased by providing appropriate support. [ABSTRACT FROM AUTHOR]

The opinions of patients with allergic skin diseases often determine their attitudes to treatment. However, little is known about the viewpoints of patients and their concerns regarding their conditions. This novel study is the first to compare relationships between the opinions of patients and their concerns regarding the severity of atopic dermatitis or chronic spontaneous urticaria and the presence or absence of biologics. We also compared and clarified the characteristics of these diseases using a questionnaire that was completed by 359 patients treated at university and city hospitals, as well as dermatology clinics. Covariance analysis was performed to compare both diseases with different backgrounds. Patients with adult atopic dermatitis were more likely than those with chronic idiopathic urticaria to believe that treatment must be continued and that the disease will not spontaneously improve. Patients with severe or poorly controlled atopic dermatitis or chronic spontaneous urticaria often had psychosomatic symptoms and also believed that the disease required continued treatment. Social factors related to wait times and medication were not associated with disease severity. Patients receiving treatment had significantly less anxiety associated with biologics than those who did not receive treatment. Patients with atopic dermatitis had higher physical and mental burden than those with chronic spontaneous urticaria. Therefore, effective treatments must be prescribed. Consideration of these disease-specific characteristics regarding the opinions and concerns of patients can improve patient satisfaction and compliance with treatment, which results in favorable outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic relapsing condition with high disease burden and impact on health-related quality of life (HRQoL). Correlations between clinician- and patient-reported outcomes tend to be poor, and limited data in Asian patients are available. Methods: ADDRESS-J was a prospective, non-interventional, longitudinal study that evaluated the real-world effectiveness and safety of AD treatment in Japanese adults (aged 20–59 years) with moderate-to-severe AD. Three clinician-reported AD severity outcomes (Investigator's Global Assessment, Eczema Area and Severity Index, and body surface area affected), three dermatological patient-reported outcomes (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and Worst Itch Numerical Rating Scale), and two general HRQoL patient-reported outcomes (5-dimension EuroQoL questionnaire and EuroQol Visual Analog Scale) were collected at baseline and every 3 months throughout the 24-month observation period. Four biomarkers were also analyzed when available (thymus and activation-regulated chemokine [TARC], lactate dehydrogenase [LDH], total immunoglobulin E [IgE], and peripheral blood eosinophil counts [PB EOS]). Spearman's correlation coefficients were calculated using all available pooled data from baseline through 24 months. Results: Correlations between the three clinician-reported outcomes were high/very high (Spearman's correlation coefficients 0.76–0.92); those between the three dermatological patient-reported outcomes were moderate (0.53–0.64), and those between the clinician-reported and dermatological patient-reported outcomes were low/moderate (0.37–0.51). Correlations between the general HRQoL patient-reported outcomes and the clinician-reported and dermatological patient-reported outcomes were negligible–moderate (0.26–0.60). Biomarker correlations with the clinician-reported and dermatological patient-reported outcomes were low/moderate for TARC and LDH (0.44–0.63), but negligible/low for PB EOS and total IgE (0.01–0.41). Conclusions: These results show that clinician- and patient-reported outcomes do not necessarily correlate well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when assessing disease severity/impact, planning treatment, and assessing response to treatment. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) Identifier UMIN000022623. Plain Language Summary: Atopic dermatitis (AD) is a long-term recurring skin disease that needs monitoring over time. Various measures (outcomes) are used to assess the severity of AD and its effect on patients. Some outcomes are based on examinations used by clinicians (doctors). Others are based on questionnaires used by patients themselves to report how severe they feel their AD is, and how it affects their lives. It is not known how well these different measures correlate with one another (how a severity score given by one outcome agrees with that given by another outcome), especially in Asian patients. This analysis used information from ADDRESS-J, a study that followed Japanese adults with moderate-to-severe AD who were treated for AD in the real world for a period of 2 years. It used a statistical method to compare three clinician-reported severity outcomes, three dermatological (skin-related) patient-reported outcomes, and two general health-related quality of life patient-reported outcomes. Agreement between the three clinician-reported outcomes was high or very high. Agreement between the three dermatological patient-reported outcomes was moderate. However, importantly, agreement between the clinician-reported outcomes and the dermatological patient-reported outcomes was low or moderate. Agreement between the general health-related quality of life outcomes and all other dermatological outcomes (whether clinician- or patient-reported) was low or moderate. The study showed that clinician-reported and patient-reported AD outcomes do not necessarily agree well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when evaluating AD, planning treatment, or judging how well patients are responding to treatment. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) places a burden on work productivity. Recently, dupilumab was approved for AD, but its impact on work productivity in Japanese patients has not been reported. Furthermore, data on the effect of long‐term treatment with dupilumab on work productivity are limited. We investigated the work productivity and activity in Japanese patients with moderate‐to‐severe AD, utilizing the Japanese version of the Work Productivity and Activity Impairment (WPAI‐AD‐Japan) questionnaire. Furthermore, we examined the impact of dupilumab on work productivity. Adult moderate‐to‐severe AD patients treated with dupilumab for more than 12 months from March 2020 to June 2022 who filled out the WPAI‐AD‐Japan questionnaire were included. Twenty‐eight adult AD patients were analysed. Absenteeism was low (mean: 5.3%), but presenteeism, work productivity loss and activity impairment were high (36.8%, 39.7%, 48.9%, respectively). Significant positive correlations were observed between work productivity loss and visual analogue scale (VAS) score of pruritus and between activity impairment and dermatology life quality index (DLQI). Dupilumab treatment significantly reduced presenteeism, work productivity loss and activity impairment at both 6 and 12 months. The extent of their amelioration was numerically higher at 12 months than at 6 months. The reduction rates in presenteeism, work productivity loss and activity impairment were positively correlated with the reduction rates in DLQI and VAS score of pruritus at 12 months. Dupilumab improved work productivity in Japanese AD patients. Long‐term remission of pruritus and improved quality of life are important for comprehensive improvement of work productivity. [ABSTRACT FROM AUTHOR]

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]

Objectives: Atopic dermatitis (AD) is aggravated by various factors, including perspiration and heat. Thus, it is recommended that AD patients wear breathable clothing to maintain disease remission. Japan has four seasons, so the ideal clothing for individuals with AD may differ throughout the year. The aim of this study was to evaluate the impact of wearing a newly developed performance fabric, named the Comfiknit Atopic Eczema® T‐shirt, which absorbs excess perspiration from the skin surface and retains moisture within the fabric. We evaluated the effects of the T‐shirts on the clinical characteristics of AD and compared the effects in summer and winter. Methods: Ten adult outpatients with AD took part in an open‐label pilot study for 4 weeks during the summer and for 4 weeks during the winter. The Eczema Area and Severity Index (EASI), the Patient‐Oriented Eczema Measure (POEM), the itch Visual Analogue Scale (VAS), the stratum corneum water content (SCWC), skin pH, and skin bacterial cultures were evaluated. A Treatment Satisfaction Questionnaire for Medication‐9 (TSQM‐9) was filled out only after the intervention. Results: The mean EASI, POEM, and itch VAS scores in both summer and winter fell after wearing the Comfiknit Atopic Eczema® T‐shirts, whereas the SCWC increased. There was no significant difference in the skin surface pH or bacterial cultures before and after the intervention. Conclusions: Wearing Comfiknit Atopic Eczema® T‐shirts helped to prevent exacerbation of AD in summer and winter. Thus, wearing T‐shirts made from performance fabric may help to maintain skin homeostasis. [ABSTRACT FROM AUTHOR]

Dupilumab was approved for treating adult patients with atopic dermatitis (AD) refractory to topical therapy in Japan in April 2018, and self‐injection of dupilumab has been available since May 2019. Subcutaneous self‐injection of medication has benefits for patients and the healthcare system. However, anxiety about self‐injection, lack of confidence, and the complicated procedure could prevent initiating self‐injection. In this study, we assessed the experience of AD patients treated with dupilumab before and after introducing self‐injection, utilizing the Self‐Injection Assessment Questionnaire (SIAQ). Adult AD patients who received dupilumab by self‐injection and had been treated for more than 3 months after initiating self‐injection in our hospital from March 1, 2020, to June 19, 2021, were included in this study. Patients rated their perceptions about self‐injections using the SIAQ before the first self‐injection and 3 months after initiating self‐injection. Data were collected retrospectively from their charts. Data on 36 patients were analyzed. The mean age was 34.1 ± 11.5 years. Twenty patients used a prefilled auto‐injector, and the others used a prefilled syringe. Scores on self‐confidence and satisfaction with self‐injection significantly improved after introducing self‐injection. Feelings about injections improved in patients over 40 years and in those who felt anxious about self‐injection. A strong correlation in scores between satisfaction with self‐injection and the ease of use was observed. The results were not affected by clinical severity, gender, or device. Our results could encourage patients who dither to introduce self‐injection of dupilumab due to anxiety and/or lack of self‐confidence about self‐injection to initiate self‐injection. [ABSTRACT FROM AUTHOR]

Background: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. Methods: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. Results: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. Conclusions: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic skin condition that is associated with significant patient burden and decreased health‐related quality of life (HRQoL). We report results of the real‐world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience study in Japanese pediatric patients, focusing on the impact of AD severity on disease burden. Methods: Children and adolescents aged 6 months to 17 years (or their caregivers/parents) completed an online survey between September 26, 2018, and March 5, 2019. Patients with diagnosed AD (i.e., met International Study of Asthma and Allergies in Childhood criteria and had a self‐reported AD diagnosis) were evaluated for disease severity using the Patient‐Oriented Eczema Measure (POEM). Impact of AD severity on AD symptoms (itching, pain, and sleep disturbance), disease flares, atopic comorbidities, healthcare resource utilization, school days missed, and HRQoL were assessed. Results: Of 5702 Japanese pediatric patients, 547 had diagnosed AD and were included in this analysis. Based on POEM scores, AD severity was clear/mild in 346 patients (63.3%), moderate in 177 (32.5%), and severe in 24 (4.4%). Across all age groups (i.e., less than 6, 6–11, and 12–17 years), increased AD severity was associated with increased AD symptom severity, number of flares, atopic comorbidities, healthcare resource utilization, and school absences, as well as worsened HRQoL. Conclusions: This population‐based study of Japanese children and adolescents showed that greater AD severity had a high impact on disease burden. [ABSTRACT FROM AUTHOR]

Background Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. Objectives To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. Methods Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. Results Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87–100%; NPV 68–100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92–100%; NPV 80–100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. Conclusions Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Objectives: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder in Japan. Dupilumab, a fully human monoclonal antibody, targets a shared subunit of the interleukin (IL)‐4 and IL‐13 receptors. Post‐marketing surveillance of the safety and effectiveness of dupilumab in adult AD patients was conducted in Japan, where the drug is also allowed for use in older adolescents (i.e., ≥15 years), and interim results are reported here. Methods: This observational, multicenter study enrolled Japanese patients with AD who initiated dupilumab between July 2018–June 2020 (UMIN‐CTR Trials Registry: UMIN000032807). Baseline demographics, clinical history, medication data and dupilumab safety and effectiveness data were collected. Results: By the data cut‐off date of March 26, 2021, information from 600 patients has been collected. All the available safety and 1‐year effectiveness data are presented. The mean (standard deviation) age was 42.0 (15.9) years, the majority (69.1%) were male, and asthma was present in 12.2%. Adverse drug reactions (ADRs) were observed in 98 patients (16.4%), including conjunctivitis (n = 40; 6.7%), conjunctivitis allergic (n = 30; 5.0%), blepharitis (n = 5; 0.8%), headache and eye pruritus (n = 4; 0.7% each) and eosinophilia (n = 3; 0.5%). Six patients experienced asthma, all of whom had a history of, or concurrent, asthma. Disease severity improved remarkably at 4 months in most patients, which was maintained up to 1 year. Conclusion: Dupilumab appears to be a safe and effective treatment for patients aged ≥15 years with moderate‐to‐severe AD in routine clinical practice in Japan. Dupilumab was well tolerated, with no new safety signals and no new‐onset asthma. [ABSTRACT FROM AUTHOR]

Allergic conjunctivitis, allergy, atopic dermatitis, birth cohort study, allergic rhinitis, food allergy, meconium-stained amniotic fluid Keywords: allergic conjunctivitis; allergic rhinitis; allergy; atopic dermatitis; birth cohort study; food allergy; meconium-stained amniotic fluid EN allergic conjunctivitis allergic rhinitis allergy atopic dermatitis birth cohort study food allergy meconium-stained amniotic fluid 1 5 5 05/30/23 20230501 NES 230501 PEER REVIEW The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/pai.13956. Data on MSAF at childbirth were retrieved from medical record transcripts, by answering yes or no to the question "Was there MSAF?". [Extracted from the article]

Introduction: Keloids are a fibroproliferative, multifactorial, cutaneous disorder whose pathophysiology is not completely understood. Various factors such as high blood pressure, pregnancy, female gender, mechanical tension of local sites, and prolonged wound healing are known to worsen keloids. Childhood-onset keloids are keloids that form before 10 years of age, before various factors in adulthood come into play, and thus studying childhood-onset keloids may provide additional insight into the underlying mechanisms that lead to keloid formation. Methods: Retrospective chart review was performed on all patients with childhood-onset keloids who were evaluated at our plastic surgery clinic (one of the largest keloid referral centers in Japan) over a 1-year period. Results: Of the 1443 patients with diagnosis of keloids, 131 patients had childhood-onset keloids. Of these, 106 patients (80.9%) were female, 38.9% of patients had family history of keloids, and 48.9% of patients had allergies or allergy-related conditions (asthma, atopic dermatitis, or allergic rhinitis). Vaccination (47.5%) and chickenpox (19.9%) were the most common triggers. Of vaccinations, BCG was the most common trigger. The majority of keloids from BCG were in female patients (92.9%). The most common location was the chest in male patients (30.0%) and the arm in female patients (41.1%). Conclusion: To our knowledge, this is the largest report in the literature on childhood-onset keloids. There was overall female predominance in childhood-onset keloids, and even more significant female predominance in BCG-induced keloids. [ABSTRACT FROM AUTHOR]

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Pediatric atopic dermatitis (AD) can negatively impact the family quality of life (QoL). We report data from the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE) study in Japanese pediatric patients, focusing on disease impact on family QoL. Children and adolescents aged 6 months to <18 years completed an online survey between September 2018–December 2019. The impact of disease severity on family QoL and its effect on parents' time were assessed using the dermatitis family impact (DFI) questionnaire. The impact of a family history of allergic conditions, current residency, second-hand smoke exposure, and household pets on AD prevalence and severity was also assessed. Family QoL decreased as AD severity increased, particularly in families with children aged <6 years; but had the greatest impact on sleep and tiredness in families with children aged <12 years. Parents spent at least 4.6 h/week caring for children <6 years, including those with mild symptoms. Most children (>80%) had a family history of allergic conditions; AD prevalence was increased in those exposed to second-hand smoke or household pets. This study demonstrated that pediatric AD in Japanese individuals has negative impacts on family QoL and that family and household environments can influence pediatric AD prevalence. [ABSTRACT FROM AUTHOR]

Background: Little is known about the association between maternal use of heated tobacco products (HTPs) during pregnancy and the onset of allergy among offspring. This study aimed to determine whether maternal HTP smoking is associated with allergy in their offspring and to evaluate the potential dose–response association. Methods: In this web‐based, cross‐sectional survey conducted in July and August 2021 in Japan, we investigated 5688 pairs of postpartum women and infants (<3 years). Clinical diagnoses of infant asthma, rhinitis, conjunctivitis, or atopic dermatitis were reported. Using multilevel Poisson regression, we estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) of allergy in infants with HTP smoking categories cross‐classified by pregnancy periods, and adjusted for potential covariates including maternal cigarette smoking and partner's smoking status. Non‐smokers served as the reference group. Results: In total, 2.4% women smoked HTPs during pregnancy. Allergy occurred in 7.8% of the infants. The prevalence of allergy increased among the offspring of current HTP smokers during pregnancy at 15.2% (PR = 1.98, 95% CI 1.28–3.05); this association was the most pronounced during the first trimester but attenuated before pregnancy and postpartum. Dose–response associations were observed, for example a one‐unit increase in daily maternal HTP use during pregnancy was associated with a 5% increase in allergy onset. Sub‐group analyses excluding cigarette smokers during pregnancy and sensitivity analyses using the International Study of Asthma and Allergies in Childhood questionnaire showed a similar pattern. Conclusions: Maternal HTP smoking during pregnancy is associated with allergy in the offspring. [ABSTRACT FROM AUTHOR]

Background: Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. Methods: Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18‐month‐old infants and the prevalence of allergic diseases when they were aged 3 years. Results: Data for 74,349 children were analyzed. Most 18‐month‐old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05–1.34; sometimes: aOR 1.72, 95% CI 1.46–2.03; seldom: aOR 1.99, 95% CI 1.58–2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. Conclusions: Frequent soap use when bathing 18‐month‐old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well‐designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Currently, the association between the duration of neonatal phototherapy and the risk of allergic disorders has not been reported. This observational cohort study aimed to examine the association between allergic disorders, including food allergies, that are present before 3 years of age and the duration of phototherapy using the nationwide birth cohort data. Methods: The Japan Environment and Children's Study was a nationwide birth cohort study. Data of 77,064 infants aged 1 year, 1.5 years, 2 years, and 3 years were analyzed. We divided the participants into three groups: no phototherapy, short phototherapy (1–24 h), and long phototherapy (>24 h) and evaluated the cumulative incidence of allergic disorders before 3 years of age, including asthma, atopic dermatitis, and food allergies. Logistic regression analysis was performed to assess the impact of phototherapy duration on the cumulative incidence of allergic disorders. Results: After adjustment for potential risk factors, long phototherapy was found to be positively associated with food allergies at age 2 years (OR: 1.16; 95% CI: 1.01–1.33) and all allergic disorders at age 3 years (OR: 1.12; 95% CI: 1.01–1.24), including food allergies (OR 1.18; 95% CI: 1.04–1.35). Conclusion: A long duration of neonatal phototherapy was positively associated with the risk of allergic disorders, especially food allergies. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is reported to be more prevalent in children who were born in autumn than in spring. Here, we investigated how early the association between season of birth and eczema or AD can be observed in the postnatal period. We also examined whether specific prevalence outcomes for infant eczema and AD differed according to sex and maternal history of allergic disease in a large Japanese cohort. Methods: Using data of 81,615 infants from the Japan Environment and Children's Study, we examined the associations of birth month or season with four different outcomes—eczema at 1 month, 6 months, and 1 year of age and physician-diagnosed AD up to 1 year of age—using multiple logistic regression analysis. We also analyzed the effect of maternal history of allergic disease on these outcomes stratified by infant sex. Results: The risk of eczema at 1 month was highest in infants born in July. In contrast, infants born in autumn had higher risks of eczema at 6 months (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 2.10–2.30) and at 1 year (aOR, 1.08; 95% CI, 1.02–1.14) and of physician-diagnosed AD up to 1 year of age (aOR, 1.33; 95% CI, 1.20–1.47) compared with infants born in spring. Eczema and AD were more prevalent in infants with a maternal history of allergic disease, particularly boys. Conclusions: Our findings suggest that the prevalence of AD is associated with the season of observation. Eczema is prevalent in infants born in autumn, and this phenomenon was observed in infants as young as 6 months old. The risk associated with being born in autumn was particularly clear in boys with a maternal history of allergic disease. Trial registration: UMIN000030786 [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic eczematous disease with severe pruritus. Janus kinase (JAK) inhibitors, upadacitinib, baricitinib, and abrocitinib, are systemic treatments for AD. The outcomes of switching from one JAK inhibitor to another have not been examined. We assessed the outcomes of switching from baricitinib 4 mg to upadacitinib 30 mg in Japanese patients with moderate-to-severe AD. Twenty patients treated with baricitinib 4 mg, showing insufficient response or adverse events, were switched to treatment with upadacitinib 30 mg. We evaluated total eczema area and severity index (EASI), EASI at head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and peak pruritus numerical-rating scale (PP-NRS) at baseline (start of baricitinib), weeks 0 (time of switching), and 4 and 12 after switching. Total EASI, EASI at each anatomical site, EASI of each clinical sign, and PP-NRS were markedly reduced at weeks 4 or 12 compared to week 0. Achievement rates of more than 75% or 90% reduction of EASI from baseline significantly improved after switching. Switching from baricitinib 4 mg to upadacitinib 30 mg effectively improved rash and pruritus. [ABSTRACT FROM AUTHOR]

Upadacitinib is an oral Janus kinase (JAK) 1 inhibitor approved in Japan for moderate-to-severe atopic dermatitis (AD), and it provides a high therapeutic efficacy. We compared the therapeutic effects of upadacitinib on skin rashes of individual anatomical sites, head and neck, upper limbs, lower limbs, and trunk in patients with AD. From August 2021 to December 2022, 65 Japanese patients with moderate-to-severe AD (aged ≥ 12 years) were treated with oral once daily upadacitinib 15 mg plus twice daily topical corticosteroids of moderate-to-strongest classes. The eczema area and severity indexes (EASIs) of individual sites decreased significantly at weeks 4, 12, and 24 compared to those at week 0 in parallel to total (whole body) EASI. The achievement rates of EASI 75 at week 24 and of EASI 90 at week 12 of lower limbs were significantly higher than those of trunk. The percent reductions of EASI of lower limbs at weeks 12 and 24 were significantly higher than those of head and neck and of trunk. Among the four anatomical sites, the treatment responsiveness to upadacitinib in lower limbs appeared the highest, while those in trunk and in head and neck appeared relatively lower. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is an inflammatory disease causing severe skin itching. Data on patient–physician disconnect on treatment satisfaction in patients with AD in Japan are limited. We investigated patient–physician disconnect on treatment satisfaction in AD and if it influences treatment patterns, clinical characteristics, and patient-reported outcomes (PROs). Methods: Data were drawn from the Adelphi AD Disease Specific Programme (DSP), a real-world, point-in-time survey of physicians and patients with AD conducted in Japan from April to July 2019. Patients and physicians were grouped according to level of treatment satisfaction ("extremely satisfied" to "extremely dissatisfied"); with any level of dissatisfaction recorded as "less than satisfied." Data were collected on treatment patterns, clinical characteristics, and PROs including the Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), EQ-5D-3L questionnaire, and Work Productivity and Activity Impairment (WPAI) questionnaire. Results: Data were provided by 184 patients with AD and 56 physicians; 72.8% of patient–physician pairs reported a fair (kappa coefficient: 0.40) level of agreement on treatment satisfaction, 51.6% of patient–physician pairs were both satisfied, and 21.2% were both less than satisfied. Satisfied physicians prescribed a mean 1.2 fewer treatments than dissatisfied physicians (p < 0.05). Cases where both physician and patient were less than satisfied or where patients were less satisfied than their physicians reported the worst PROs, DLQI (both less than satisfied: mean 10.7 versus patient less satisfied than physician: 10.6 versus overall: 7.9), POEM (19.5 versus 17.3 versus 17.0), EQ-5D-3L (0.82 versus 0.81 versus 0.87) (all, p < 0.05). Work impairment was highest when both patient and physician were less than satisfied (p < 0.05). Physicians cited treatment efficacy and patients cited efficacy and usability as main reasons for dissatisfaction. Conclusion: Overall, 12.0% of patients were less satisfied with their AD treatment than the physician, demonstrating some of the worst PROs, suggesting unmet need that could be improved by better patient–physician communication. [ABSTRACT FROM AUTHOR]

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch. Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS). Results: A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112. Conclusion: UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents. Trial Registration: ClinicalTrials.gov identifier, NCT03661138. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib is an oral selective Janus kinase (JAK)1/JAK2 inhibitor approved in Japan and the European Union for the treatment of atopic dermatitis (AD). The aim of this study is to report pooled safety data for baricitinib in the Japanese subpopulation of the clinical development program in moderate-to-severe AD. Methods: This analysis included participant-level safety data from five double-blind, randomized clinical studies and one double-blind, randomized, long-term extension study, reported in three datasets for the Japanese subpopulation: (1) placebo-controlled, (2) baricitinib 2 mg and 4 mg extended ("2-mg—4-mg extended"), and (3) all baricitinib doses ("All-bari-AD"). The data cutoff was 13 December 2019. Safety outcomes included treatment-emergent adverse events, adverse events of special interest, and abnormal laboratory changes. Proportions of participants with events and incidence rates were calculated. Results: Data were collected for 341 participants from Japan who received baricitinib for 371.7 participant-years (median duration 371.0 days). In the placebo-controlled dataset, the frequencies of serious infections and herpes zoster were low and similar between treatment groups, and the incidence of treatment-emergent infections, in particular herpes simplex, was higher in the baricitinib groups compared with the placebo group. No gastrointestinal perforations, tuberculosis, positively adjudicated cardiovascular events, deep vein thrombosis, or pulmonary embolism were reported with exposure up to 2 years in the All-bari-AD dataset. There were no deaths in the Japanese subpopulation. Conclusions: This integrated safety analysis in the subpopulation of Japanese participants is consistent with the established safety profile of baricitinib in the global study population with moderate-to-severe AD. Clinicaltrials.gov identifiers: NCT02576938, NCT03334396, NCT03334422, NCT03428100, NCT03733301, and NCT03334435. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects. • Determinants of prenatal indoor risk factors on childhood eczema were investigated. • Gas heater, parquet flooring, and insecticide use are risks for childhood eczema. • Mold exposure before infant birth is a risk factor, regardless of parental heredity. • Prenatal mold exposure is a risk factor, regardless of postnatal mold exposure. • Reducing mold during pregnancy may help prevent childhood eczema in early life. [ABSTRACT FROM AUTHOR]

Objective: Itch is a common symptom of atopic dermatitis (AD), however, there is limited evidence of the frequency and association of skin pain alongside itch. This study assessed the incremental dual burden and impact of itch and skin pain on satisfaction, quality of life and work productivity in patients with AD in Japan.Methods: Data were drawn from the 2020 Adelphi AD Disease Specific Programme, a point-in-time survey of dermatologists (n = 56) and their patients with history of moderate/severe AD (n = 265). Patients were grouped accordingly: no itch/skin pain (No I/SP, reference group, n = 89), itch/no skin pain (I-only, n = 71), and itch and skin pain (I + SP, n = 26). Descriptive analyses were performed alongside a range of regression models, dependent on outcome variables.Results: I + SP patients had a 4.97-point worse POEM score (p = .005) and 14.5% more overall work impairment (p = .034) versus the reference group. I-only and I + SP patients were 8.92 and 23.5 times more likely, respectively, to experience sleep disruption on a day-to-day basis (both p < .001). I + SP patients were 4.6 times more likely to be bothered by their symptoms (p = .034), had a mean EASI score 6.7 points higher (p = .008) and had 1.39 more areas affected (p = .001). I + SP patients were 7.26 times more likely to express dissatisfaction with lack of improvement in their condition and 8 times more likely to be dissatisfied with convenience of treatment (both p < .05).Conclusion: This dissatisfaction, alongside variations in reported symptomatic burdens, suggests that physicians could consider alternative and/or novel therapeutic approaches for the management of both itch and skin pain. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of scallop oil (SCO) on atopic dermatitis (AD) -like symptoms induced by mite allergens in the dorsal and ear skins of NC/Nga mice compared to those of refined corn oil and krill oil (KO). SCO, rich in n -3 polyunsaturated fatty acids and phospholipids, was prepared from the internal organs of Japanese giant scallop, an underutilized fishery resource in Japan. Results showed that SCO intake improved AD-like symptoms, including ear edema, ear thickness, and transepidermal water loss of dorsal skin, and tended to decrease the scratching behavior, whereas KO intake did not. Further, SCO intake decreased the degranulated mast cell count and increased the tight junction protein claudin-1 expression, which is important for the barrier function, in the dorsal skin compared to refined corn oil intake. SCO improved the AD-like symptoms by suppressing mast cell degranulation and strengthening the barrier function of dorsal skin in NC/Nga mice. [ABSTRACT FROM AUTHOR]

We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods. Infants 3–4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837). A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116–0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant. Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives: To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study -demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods: The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged =12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results: Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion: Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

Introduction: Treatment satisfaction in patients with atopic dermatitis (AD) has been investigated in several studies, but the desire for alternative treatment options is unclear and has not been previously evaluated. We conducted a cross-sectional, web-based survey aimed at evaluating the desire for alternative treatment options in adults with AD from a patient registry in Japan. Methods: Main eligibility criteria were adults aged ≥ 18 years with AD who were receiving treatment with topical corticosteroids (TCS) and not systemic therapy. Questionnaires included the Patient Oriented Eczema Measure (POEM) and pruritus Numeral Rating Scale. The proportion of patients with a desire for an alternative treatment option was assessed, overall (Overall Desire) and by specific type of alternative treatment option (Specific Desire), including change in medication, hospital transfer, and complementary and alternative medicine (CAM) use. Patient background factors associated with desire were evaluated using multivariate logistic regression. Results: Of the 1500 patients included in the analysis, 91.5% (n = 1372) had an Overall Desire, with the most common Specific Desire being a change in medication (n = 1213, 80.9%), followed by CAM (n = 593, 39.5%) and hospital transfer (n = 429, 28.6%). Dissatisfaction with current treatment was significantly (p < 0.05) associated with Overall Desire and Specific Desire (p < 0.001 each). Severe disease according to POEM was significantly associated with Overall Desire and a change in medication (p < 0.001 each). Conclusions: A high proportion of Japanese patients with AD being treated with TCS had a desire for alternative treatment options. The desire was greatly affected by patients' satisfaction with their current treatment and perception of disease severity. These findings highlight the importance of assessing patients' satisfaction or perception of disease severity, and facilitating early discussions between patient and doctor on their available treatment options, including new treatment options. [ABSTRACT FROM AUTHOR]

Objective: To determine the climate conditions that affect the incidence of atopic dermatitis from infancy to 3 years old. Study design: We analyzed 100,303 children born from 2011 to 2014 for follow-up until 3 years old using cohort data from the Japan Environment and Children's Study. The study included 15 Regional Centers, including 19 prefectures across Japan. We used meteorological data of the Japan Meteorological Agency. We calculated the hazard ratio (HR) of the standard deviation and low vs. high mean values of several climate conditions in children in their first 6 months of life to determine the incidence of atopic dermatitis. Results: The Kaplan–Meier curve showed that children born in the months of October to December had the highest incidence of atopic dermatitis. Among climate conditions, a one standard deviation increase in the temperature (HR = 0.87), minimum temperature (HR = 0.87), and vapor pressure (HR = 0.87) showed the lowest HRs for the incidence of atopic dermatitis. These results were confirmed by an analysis by strata of the birth season. A low vapor pressure (HR = 1.26, p<0.0001) and the combination of a low mean temperature or low mean minimum temperature and low vapor pressure (HR = 1.26, p<0.0001) were associated with the highest incidence of atopic dermatitis. These results were consistent when they were adjusted for a maternal and paternal history of allergy and the prefecture of birth. Conclusion: Among climate conditions, a low vapor pressure is the most strongly associated with a high incidence of atopic dermatitis. Measuring vapor pressure may be useful for preventing atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background and Objective: Abrocitinib is a Janus kinase 1 inhibitor in development for the treatment of atopic dermatitis (AD). This work characterized orally administered abrocitinib population pharmacokinetics in healthy individuals, patients with psoriasis, and patients with AD and the effects of covariates on abrocitinib exposure. Methods: Abrocitinib concentration measurements (n = 6206) from 995 individuals from 11 clinical trials (seven phase I, two phase II, and two phase III) were analyzed, and a non-linear mixed-effects model was developed. Simulations of abrocitinib dose proportionality and steady-state accumulation of maximal plasma drug concentration (Cmax) and area under the curve (AUC) were conducted using the final model. Results: A two-compartment model with parallel zero- and first-order absorption, time-dependent bioavailability, and time- and dose-dependent clearance best described abrocitinib pharmacokinetics. Abrocitinib coadministration with rifampin resulted in lower exposure, whereas Asian/other race coadministration with fluconazole and fluvoxamine, inflammatory skin conditions (psoriasis/AD), and hepatic impairment resulted in higher exposure. After differences in body weight are accounted for, Asian participants demonstrated a 1.43- and 1.48-fold increase in Cmax and AUC, respectively. The overall distribution of exposures (Cmax and AUC) was similar in adolescents and adults after accounting for differences in total body weight. Conclusions: A population pharmacokinetics model was developed for abrocitinib that can be used to predict abrocitinib steady-state exposure in the presence of drug–drug interaction effects or intrinsic patient factors. Key covariates in the study population accounting for variability in abrocitinib exposures are Asian race and adolescent age, although these factors are not clinically meaningful. Clinical Trial Numbers: NCT01835197, NCT02163161, NCT02201524, NCT02780167, NCT03349060, NCT03575871, NCT03634345, NCT03637790, NCT03626415, NCT03386279, NCT03937258. Plain Language Summary: Abrocitinib is a drug approved in the UK and Japan for the treatment of atopic dermatitis. A population pharmacokinetic model for abrocitinib was developed based on data from 11 clinical trials that included 995 healthy individuals or patients with atopic dermatitis or psoriasis. Simulations of different patient factors, such as age, race, sex, body weight, liver function, and drug–drug interactions, were tested to examine differences in abrocitinib drug levels achieved in the body. The results of these simulations indicate that although there are some differences in abrocitinib exposure, no dose adjustments of abrocitinib are necessary based on these factors. [ABSTRACT FROM AUTHOR]

Objectives: Delgocitinib is a small‐molecule JAK inhibitor that has recently been approved in Japan as the world's first topical JAK/STAT pathway inhibitor for the treatment of atopic dermatitis (AD). In this study, the effects of delgocitinib 0.5% ointment treatment on skin rash severity and skin‐barrier function were examined. Methods: Adult Japanese patients with mild‐moderate AD (n = 23) were recruited into the trial. Healthy subjects (n = 10) were examined in parallel. The effects of four weeks of treatment with delgocitinib 0.5% ointment on the partial eczema area and severity index (pEASI) score, stratum corneum hydration (SCH), and trans‐epidermal water‐loss (TEWL) were examined. Patient reported effects of the treatment were assessed by a questionnaire. Results: Four weeks of treatment showed a statistically significant improvement (p <.001) in pEASI score of 61.8%, ±54.0 (mean%, SD) compared to baseline in AD patients. Improvement in SCH at four weeks (37.6AU, ±11.5 (mean, SD), p <.001) was achieved in AD patients compared to baseline (SCH = 24.9AU, ±8.8 (mean, SD)). A trend toward reduction in TEWL over time was seen in the active treatment group (TEWL = 9.1 g/h/m2 at baseline, 7.1 g/h/m2 at two weeks, and 6.9 g/h/m2 at 4 weeks). The pEASI score and SCH and TEWL values improved from two‐to‐four weeks treatment. Patients reported perceived improvements after four weeks of treatment on all parameters associated with skin condition. No safety concerns were identified. Conclusions: Treatment with delgocitinib 0.5% ointment was well tolerated and showed improvements of both eczema and SCH in adult AD patients. [ABSTRACT FROM AUTHOR]

Background: Maternal mental health problems in each of the prenatal period and postnatal period have been demonstrated as possible risk factors for atopic dermatitis (AD) in children. However, the cumulative impacts of maternal psychological distress in the prenatal and postnatal periods on AD in children remain unclear. This study examined the association between cumulative exposure to maternal psychological distress in the prenatal and postnatal periods and the development of AD in children.Methods: Data were derived from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. In total, 8377 mother-child pairs in which the child had no AD at the age of 1 year were analyzed. Maternal psychological distress in early pregnancy and 1 year after delivery was defined as a K6 score ≥ 5, and the participants were categorized into four groups: no psychological distress in both the prenatal and postnatal periods; only the prenatal period; only the postnatal period; and both periods. The development of AD was defined as the presence of AD in a 2-year-old child without AD reported at the age of 1 year using the International Study of Asthma and Allergies in Childhood questionnaire. Generalized linear model analyses were conducted to examine the association between maternal psychological distress and the development of AD in children adjusted for age at delivery, educational attainment, smoking status in pregnancy, maternal history of AD, paternal history of AD, parity, maternal body mass index, and child sex.Results: Between the ages of 1 and 2 years, 14.0% of children developed AD. Maternal psychological distress in both prenatal and postnatal periods was associated with an increased risk of AD in children compared to no psychological distress in both periods (relative risk (RR), 95% confidence interval (CI): 1.34, 1.20-1.47). Maternal psychological distress in only the postnatal period was associated with an increased risk of AD in children (RR, 95% CI: 1.23, 1.07-1.39), but not in only the prenatal period (RR, 95% CI: 1.14, 0.98-1.30).Conclusions: Cumulative exposure to maternal psychological distress in the prenatal and postnatal periods was associated with the development of AD in children. [ABSTRACT FROM AUTHOR]

The number of patients with atopic dermatitis is on the rise worldwide, and Japan is no exception. According to recent estimates of the percentage of patients with atopic dermatitis in Japan by age, the majority of patients are between 20 and 44 years old. Because the peak age of onset of atopic dermatitis is during infancy, many patients may experience prolonged symptoms from infancy to adulthood. A prolonged clinical course also increases the burden of atopic dermatitis on affected patients. Decreased productivity due to work disruptions, reduced daily activity, higher direct medical costs, fatigue, and daytime sleepiness due to sleep disturbances are typical burdens on patients with atopic dermatitis. In order to reduce these burdens, it is necessary to shorten its clinical course and achieve long-term control without relying on medications, possibly by using avoidance or coping measures of aggravating factors. Typical aggravating factors of atopic dermatitis include irritant dermatitis, food allergy in children, sweating, and psychological stress in adults. Food allergy places a heavy burden on the quality of life of affected patients and their families. The effectiveness of educational interventions for sweating and psychological stress is unclear. We must also evaluate the economic burden and cost-effectiveness of interventions on the patient as aggravating factors to be addressed. [ABSTRACT FROM AUTHOR]

Background: Juzentaihoto (JTT) is a Kampo prescription that has been used clinically for treating skin diseases such as atopic dermatitis in Japan. We have previously studied the anti-allergic effects of JTT on 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) in mice and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying the anti-allergic actions of JTT is obscure. Methods: We investigated the mechanism underlying the anti-allergic effects of JTT using a TNCB-induced murine CHS model and adoptive cell transfer experiments. Results: We showed that the anti-allergic effects of JTT are due to inhibition of effector T-cell activation and induction and/or activation of regulatory T cells. Furthermore, ex vivo experiments confirmed the effect of JTT on the activation of effector T cells and regulatory T cells, as interferon-γ production decreased, whereas interleukin (IL)-10 production increased, in the cultured lymphocytes obtained from 5% TNCB-sensitized mice treated with anti-CD3ε and anti-CD28 monoclonal antibodies. Flow cytometry showed that the CD4+CD25+Foxp3+, CD4+CD25+Foxp3−, and CD8+CD122+ cell population increased after oral administration of JTT. Finally, the anti-allergic effect of JTT by inducing and/or activating regulatory T cells (Tregs) was confirmed to be mediated by IL-10 through in vivo neutralization experiments with anti-IL-10 monoclonal antibodies. Conclusion: We suggested that JTT exerts anti-allergic effects by regulating the activation of effector T cells and Tregs involved in murine CHS model. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5. Methods: Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder. Results: At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10–50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints. Conclusion: Baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy. Clinical Trial Registration: NCT03435081. Plain Language Summary: Baricitinib is a medication that helps a dysregulated immune system readjust. This leads to improvements in the inflammatory disease atopic dermatitis (AD). Baricitinib is approved for adults with moderate-to-severe AD in over 40 countries. In the ongoing study BREEZE-AD5, baricitinib 2 mg improved moderate-to-severe AD in patients who previously did not respond to or could not tolerate topical corticosteroids. Understanding which patients are likely to benefit most from a medication can improve patient experience with treatment. It can also ensure that only patients who are likely to benefit from a medication are exposed to it. This analysis aimed to identify patients who are most likely to benefit from baricitinib 2 mg in BREEZE-AD5, using an approach based on baseline body surface area (BSA) affected and early clinical improvement. We showed that patients with moderate-to-severe AD affecting between 10% and 50% of their BSA account for the majority of patients who respond to baricitinib 2 mg after 16 weeks of treatment. Clinical assessment of skin inflammation or itch in patients after 4–8 weeks of initiation of baricitinib 2-mg treatment further improved the ability to identify patients who are most likely to benefit from long-term therapy. This proposed clinical tailoring approach of baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may allow for the treatment of patients who are most likely to respond to therapy, and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg. [ABSTRACT FROM AUTHOR]

Skin inflammation leads to altered cytokine/chemokine production and causes systemic inflammation. The systemic mechanism of atopic dermatitis (AD) is recognized to affect systemic metabolism. This study aimed to examine the relationship between early-onset persistent eczema and body weight, height, and body mass index (BMI), in addition to food allergy in a birth cohort among infants. This study design was a nationwide, multicenter, prospective birth cohort study—the Japan Environment and Children's Study (JECS). Generalized linear models were fitted for z scores of weight, height, BMI, and food allergy to evaluate the relationship between eczema and these outcomes for infants at age1, 2, and 3 years. Persistent eczema was negatively associated with height at the age of 2 years (estimated coefficient, −0.127; 95% confidence interval [CI], −0.16 to −0.095) and 3 years (−0.177; 95% CI, −0.214 to −0.139). The same tendency was also observed with weight and BMI. Early disease onset at younger than 1 year and persistent eczema had the strongest association with development of food allergy at age 3 years (OR, 11.794; 95% CI, 10.721–12.975). One phenotype of eczema with early-onset and persistent disease creates a risk of both physical growth impairment and development of food allergy. Infants who present with the early-onset and persistent type of eczema should be carefully evaluated daily for impaired physical growth and development of food allergy. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to assess changes in the real‐world treatment of atopic dermatitis (AD) in Japan. Methods: Patients from the JMDC Claims Database with ≥1 confirmed diagnosis of AD, an identifiable medical care start date for AD, and ≥2 AD–related treatments on separate dates between January 1, 2005, and May 31, 2019, were included; data were analyzed on a yearly basis. Results: In total, 411,102 patients were included. The average age of patients increased from 12.0 to 18.8 years between 2005 and 2017. In any given year, the prevalence of AD was highest in patients aged <2 years and lowest in patients aged ≥50 years. Dermatology (65.1%‐69.5% from 2005 to 2017) and clinics (92.3%‐93.4%) were the main department and medical facility, respectively, providing daily medical care for AD. The proportion of patients who were given the thymus and activation‐regulated chemokine test increased from 2008 to 2017 (0.03%‐3.5%). From 2005 to 2017, the proportion of patients who received moisturizer (68.8%‐79.1%), topical calcineurin inhibitors (8.2%‐17.8%), very strong topical corticosteroids (26.0%‐40.6%), strongest topical corticosteroids (3.5%‐7.8%), cyclosporine (0.01%‐0.3%), or phototherapy (0.06%‐1.8%) increased, and the proportion of patients who received topical non‐steroidal anti‐inflammatory drugs (12.0%‐3.1%) decreased. Annual costs for medication associated with AD per person/visit increased between 2005 and 2017; however, the ratio of medication to total cost did not. Conclusions: The results of this analysis show that Japanese patients used increasingly potent treatments for AD, and overall AD‐related medication costs increased between 2005 and 2017. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the cost‐effectiveness of delgocitinib relative to moisturization therapy in adult patients with moderate to severe atopic dermatitis. Methods: The analysis was performed by using the simulation model with the patient‐level data from a phase 3 study and its longterm extension study (QBA4‐1 Study). The analysis was conducted from the Japanese public healthcare payer's perspective and included only direct medical costs. Health outcomes were evaluated by quality‐adjusted life years. The time horizon of the analysis was one year and no discount rate was applied. In this analysis model, health states were divided into four according to the Investigator's Global Assessment score. The cost‐effectiveness was determined by the incremental cost‐effectiveness ratio using the willingness‐to‐pay threshold of 5 million JPY/quality‐adjusted life years. A probabilistic sensitivity analysis was conducted to evaluate the uncertainty of each parameter used for the analysis. Results: Total cost and quality‐adjusted life years gained were 358,810 JPY and 0.867 quality‐adjusted life years for delgocitinib, and 85,890 JPY and 0.798 quality‐adjusted life years for moisturization therapy, respectively. The incremental cost‐effectiveness ratio of delgocitinib relative to moisturization therapy was estimated to be 3.92 million JPY/quality‐adjusted life years. The probability of incremental cost‐effectiveness ratio of delgocitinib vs moisturization therapy being below 5 million JPY/quality adjusted life years was 79.1%. Conclusions: Delgocitinib was rated as a cost‐effective treatment relative to moisturization therapy in adults with moderate to severe atopic dermatitis. Data comparing the drug for reducing inflammation is required. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab was equally effective among all racial subgroups in clinical trials, but a direct comparison in daily practice is lacking. Objectives: To investigate the effectiveness of dupilumab in patients with atopic dermatitis (AD) in the Netherlands and Japan over 80 weeks of treatment. Methods: A longitudinal comparative cohort study was conducted in patients with AD who were treated with dupilumab in daily practice. We used linear mixed‐effects models to determine changes over time. Results: We found statistically significant differences in sex, disease onset, body mass index and therapeutic history between Dutch (n = 208) and Japanese (n = 153) patients. The baseline Eczema Area and Severity Index (EASI) score was higher in Japanese patients (23·8 vs. 14·8), while baseline Patient‐Reported Outcome Measures (PROMs) were higher in Dutch patients. EASI scores decreased quickly to a level indicating 'mild disease' (EASI < 7), and remained low in both countries. However, PROMs showed different trajectories with better scores in Japan. Conclusions: Dupilumab showed significant, comparable and sustained improvement of EASI scores in Japanese and Dutch patients. However, we found striking differences in the effect on PROMs between the countries, with a better outcome in Japanese patients. What is already known about this topic?In clinical trials, dupilumab was found to be equally effective among all racial subgroups; however, a direct comparison in daily practice between patients with atopic dermatitis (AD) in Japan and the Netherlands is currently lacking.Although phenotypical and immunological differences between races are described for AD, literature about the racial differences in coping mechanisms and the perception of disease in AD is lacking. What does this study add? This study showed a significant improvement of disease severity in both Japanese and Dutch patients with AD during dupilumab treatment in daily practice.In addition to racial disease‐specific differences, healthcare system‐ or culture‐related characteristics might contribute to differences in physician‐ and patient‐reported outcome measures (PROMs) between countries. What are the clinical implications of the work? Consideration of PROMs and healthcare system‐ or culture‐related characteristics, in addition to disease severity measures including the Eczema Area and Severity Index, is of added value in the evaluation of treatment effectiveness in clinical studies and in daily practice. Linked Comment: A. Taïeb and N. Katoh. Br J Dermatol 2021; 185:479–480. [ABSTRACT FROM AUTHOR]

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children's Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year. [ABSTRACT FROM AUTHOR]

Background: Soy isoflavones and their metabolites such as equol have been associated with a reduced risk of hormone-sensitive tumors and metabolic syndromes. However, individual soy isoflavones and equol levels in atopic dermatitis remain uninvestigated. Objective: The aim of this study is to compare the levels of urinary daidzein, genistein, and equol between atopic dermatitis patients and normal subjects and to examine the correlation between equol concentration and the severity of clinical symptoms. Methods: A cross-sectional study was conducted at Akita University Hospital and Aso Iizuka Hospital in Japan. Fifty patients with confirmed atopic dermatitis diagnosis and 67 healthy controls were recruited. Daidzein, genistein, and equol in urine were measured by using a high-performance liquid chromatography-mass spectrometry system. Results: Urinary equol levels were significantly lower in the atopic dermatitis patients than in the healthy controls (p = 0.002). The difference was particularly noticeable in young people (6–19 years, p < 0.001). No correlations were found between urinary equol levels and the severity of clinical symptoms and laboratory data in the atopic dermatitis patients. Conclusion: Equol levels in childhood might be involved in the development of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Although pruritus is a hallmark feature of atopic dermatitis, no study has investigated the associated impact of pruritus, due to atopic dermatitis in Japan. The study aimed to evaluate the real-life burden of atopic dermatitis by pruritus severity in adult Japanese patients. The primary objective was to assess the correlation between pruritus severity and work productivity and activity impairment. A secondary objective was to characterize the impact of pruritus on quality of life and to evaluate the burden of symptoms severity and frequency. A cross-sectional internet-based survey was conducted. Eligible patients were currently employed and working adults with atopic dermatitis for at least 6 months. Stratification on pruritus severity assessed by the Worst Pruritus Numerical Rating Scale at the screening was performed to ensure that different severity groups are represented. Correlations were assessed using Spearman's rank-order correlation coefficient. Multivariate regression analyses were performed to assess the impact of pruritus severity on work productivity and quality of life. The study analyzed 370 patients. Pruritus severity significantly correlated with work impairment (Rho = 0.622, P value (H0: Rho > 0.5) <.001). A greater pruritus severity was associated with greater work productivity and activity impairment and a greater impact on quality of life, sleep, emotional state, and everyday activities. Patients with a greater pruritus severity carried a higher economic burden of treatment and were more often not satisfied with the received therapy. All data were self-reported by patients via an online survey, which is associated with the risk of misclassification for diagnosis, recall bias, and limited participation of patients. The study provides evidence that pruritus is associated with the overall disease burden and impacts many important life aspects of patients with atopic dermatitis in Japan. [ABSTRACT FROM AUTHOR]