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Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient's quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD. Methods: Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. Results: Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 − 7.8 vs − 2.8; ADvocate2 − 7.3 vs − 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 − 7.43 vs − 1.51; ADvocate2 − 4.95 vs − 0.82) and PROMIS Depression (ADvocate1 − 7.42 vs − 2.46; ADvocate2 − 4.28 vs − 2.00). Conclusions: Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline. Trial Registration: ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2). [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis is associated with intense itch, which has been shown to cause sleep disruption that significantly impacts the lives of patients with atopic dermatitis. Despite this, little is known about its burden to the healthcare system and society. This study aimed to quantify the economic burden of itch-related sleep loss in moderate-to-severe atopic dermatitis in the UK. Methods: A literature-based decision-analytic model was developed from a healthcare payer and societal perspective. The model quantifies the economic burden by linking the severity of itch to the number of days of sleep disruption. The model captures the direct costs of healthcare resource utilization and treatment alongside the indirect costs of productivity loss from absenteeism and presenteeism at work over a 5-year time horizon. The patient population considered was patients aged ≥ 15 years with moderate-to-severe atopic dermatitis and itch-related sleep disruption. Results: The model estimated that itch-related sleep disruption as a result of moderate-to-severe atopic dermatitis would affect an average of 821,142 people over the time horizon (2022 to 2026). This translates into an average net economic burden of £3.8 billion (£4687 per patient), with an average of 172 million days being affected by sleep disruption per year in the UK. The greatest contributor to the annual average net economic burden was productivity loss from absenteeism and presenteeism, each accounting for 34%. The direct costs (treatment costs and healthcare resource use) accounted for 32% of the net economic burden. The results showed a high and gradually increasing economic burden over the 5-year time horizon. Conclusions: Sleep disruption has a high economic burden and reducing itch may provide substantial direct and indirect savings. Quantifying the economic burden of itch-related sleep loss may provide support for analyses to inform public health policies for treatment of atopic dermatitis, particularly within the moderate-to-severe level. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) may affect cognitive function, but studies are limited and inconsistent. The effect of AD severity on cognition remains underexplored and few previous studies have examined clinically validated or repeated measures of cognition throughout childhood. Objectives To evaluate the relationship of AD activity and severity with validated measures of general cognition in a longitudinal birth cohort. Methods We conducted cross-sectional analyses using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK cohort of 14 975 individuals followed prospectively since their birth in 1991–92. AD was assessed 11 times between the age of 6 and 166 months. Mothers were asked if their child had an 'itchy, dry skin rash in the joints and creases', and AD status was time-updated accordingly as 'never', 'maybe', 'inactive', 'active/mild' or 'active/moderate–severe'. General cognition [i.e. intelligence quotient (IQ)] was measured at 18, 49, 103 and 186 months of age using the Griffiths Mental Development Scales (GMDS), Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC) and Wechsler Abbreviated Scale of Intelligence (WASI), respectively. Multivariable linear regression was used to compare IQ with respect to nearest time-updated AD status. Secondary analyses were stratified by the presence or absence of psychiatric or learning disorders. An exploratory longitudinal analysis of IQ across all four outcome assessments was conducted using generalized estimating equations. Results No significant associations between AD status and full-scale IQ scores on the GMDS, WPPSI, WISC and WASI were observed after adjustment for sociodemographic factors, atopic comorbidities and sleep characteristics. However, at 8 years of age, WISC Performance IQ was slightly, although statistically significantly, lower among children with active/moderate–severe AD [β coefficient –2.16, 95% confidence interval (CI) –4.12 to –0.19] and Verbal IQ was slightly, but statistically significantly, higher among those with inactive AD (β coefficient 1.31, 95% CI 0.28–2.34) compared with those without AD. Analyses stratified by psychiatric or learning disorders, and exploratory longitudinal analyses of cognition revealed similar findings. Conclusions We did not find any clinically meaningful associations between AD activity and severity and general cognitive function during early childhood and adolescence. Future studies should incorporate objective measures of AD severity and investigate outcomes beyond IQ. [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]

Background: Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK. Methods: We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006‐January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups). Results: We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19). Conclusions: Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups. [ABSTRACT FROM AUTHOR]

Background: Phototherapy is used to treat atopic dermatitis (AD). Evidence for its efficacy, impact on quality of life, cost‐effectiveness and short‐ and long‐term safety with real‐life usage is weak. Objectives: We established a taskforce to examine how phototherapy is currently being used as a treatment for AD across the United Kingdom and Europe to inform our understanding and guide future research into management of patients with AD using UV‐based phototherapies. Methods: An anonymous electronic multiple‐response survey exploring phototherapy prescribing practices and experience of phototherapy modalities was developed by the study authors and sent to members of phototherapy networks from the United Kingdom and Europe. Responses were received between February and July 2021. Results: About 144 respondents from 27 European countries completed the survey. NBUVB was the most widely used [n = 138 (96%)]. Home‐based NBUVB was available in 8/27 countries (25/144 respondents, 17%). Oral psoralen‐UVA (PUVA) was more widely available than bath PUVA (n = 106, 74% vs. n = 60, 42%) and used mainly in adult patients. 49/144 (34%) of respondents had access to UVA1. Phototherapy would be considered instead of systemic treatment in 96% of adults and 82% of children for NBUVB, versus 40% of adults and 3% of children for PUVA. Starting doses, standard dosing increments, length of treatment courses, lifetime limits for treatments and thresholds for performing annual skin assessments varied between responders. Conclusions: NBUVB was the most widely used phototherapy for AD in adult and paediatric patients, while PUVA and UVA1 were less used. Prescribing practices varied considerably, highlighting the lack of consensus practice in many different aspects of phototherapy for the treatment of AD in children and adults. This indicates that further studies are required to determine optimal phototherapeutic regimens for AD and informs our understanding of parameters that should be included in future high‐quality randomized controlled trials (RCT) of phototherapy. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) may be associated with an increased burden of neuropsychiatric outcomes such as anxiety and depression, but longitudinal data on the impact of AD severity is lacking, and a comprehensive assessment of neuropsychiatric disease in adults with AD is needed. Objectives: Determine risk of incident neuropsychiatric disease among adults with AD by severity. Methods: A cohort study using electronic health records data from UK general practices from 1994 to 2015. Adults (≥18 years) with AD were matched on age, practice and index date to patients without AD. AD severity was categorized using treatments and dermatology referrals. Outcomes were incident anxiety, depression, bipolar disorder, schizophrenia, attention‐deficit/hyperactivity disorder (ADHD), autism, obsessive‐compulsive disorder (OCD), suicidality and completed suicide. Results: Comparing 625,083 adults with AD to 2,678,888 adults without AD, AD was associated with higher risk of anxiety [HR 1.14 (1.13–1.15)], depression [1.14 (1.13–1.15)] and OCD [1.48 (1.38–1.58)] across all severities. Mild or moderate AD was also associated with higher risk of autism, ADHD, bipolar disorder and suicidality. Conclusions: Atopic dermatitis is associated with a higher risk of multiple neuropsychiatric conditions, but these risks differ by specific condition and AD severity. Clinicians should inquire about mental health in patients with AD. [ABSTRACT FROM AUTHOR]

Background: The English Cocker Spaniel (ECS) is one of the most popular dog breeds in the UK but information on disorder predisposition and protection is limited. Using anonymised veterinary clinical data from the VetCompass™ Programme, this study aimed to compare disorder predisposition and protection between the ECS and the remaining dogs under primary veterinary care in the UK during 2016. Electronic patient records for random samples of ECS and non-ECS were reviewed. The most common disorders diagnosed during 2016 were extracted and compared using multivariable logistic regression, controlling for confounders. Results: The analysis included random samples of 2510/10,313 (24.3%) ECS and 7813/326,552 (2.39%) non-ECS. After accounting for confounding by age, sex, bodyweight within breed-sex, insurance status and veterinary practice group, the ECS had increased odds of 21/43 (48.85%) disorders at fine-level precision, with highest odds for aural discharge (odds ratio (OR) 14.66, 95% confidence interval (CI): 7.73–30.90, P < 0.001) and keratoconjunctivitis sicca (OR 7.64, 95% CI: 4.33–14.14, P < 0.001) and lowest odds for atopic dermatitis (OR 0.14, 95% CI: 0.05–0.31, P < 0.001) and allergy (OR 0.14, 95% CI: 0.06–0.28, P < 0.001). Conclusions: This study provides evidence for strong predisposition to aural and ocular disorders and protection from hypersensitivity disorders in the ECS. These results can aid dog owners, breeders, and veterinarians to better monitor health in ECS, and promote earlier diagnosis with improved prognosis. Further, the results can help breeding organisations establish key priorities the health-based reforms of the ECS. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta‐analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk. Objectives: To assess the potential causative link between AD and 14 site‐specific cancers in a two‐sample randomization study. Methods: From the largest genome‐wide association study (GWAS) of AD (10,788 cases and 30,047 non‐cases), genetic variants highly associated (p < 5 × 10−8) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n = 442,239) and the FinnGen study (n = 218,792), were employed to assess genetic associations with 14 site‐specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta‐analyses. Results: We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After the Benjamini–Hochberg correction, the inverse‐variance weighted method indicated no association between AD and overall cancer risk in both the UK Biobank (OR, 1.00; 95% CI, 0.94–1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92–1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site‐specific cancers. Conclusions: Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is a common chronic inflammatory skin condition. While other chronic inflammatory conditions are associated with increased risk of venous thromboembolism (VTE), associations between AD and VTE have not been established. Objectives We examined whether AD is associated with an increased risk of VTE in a population-based study. Methods Electronic health records were extracted from UK general practices contributing to the Optimum Patient Care Research Database (1 January 2010 to 1 January 2020). All adults with AD were identified (n = 150 975) and age- and sex-matched with unaffected controls (n = 603 770). The risk of VTE, consisting of pulmonary embolism (PE) or deep-vein thrombosis (DVT), was compared in people with AD vs. controls using Cox proportional hazard models. PE and DVT were examined separately as secondary outcomes. Results We identified 150 975 adults with active AD and matched them with 603 770 unaffected controls. During the study, 2576 of those with active AD and 7563 of the matched controls developed VTE. Individuals with AD had a higher risk of VTE than controls [adjusted hazard ratio (aHR) 1.17, 95% confidence interval (CI) 1.12–1.22]. When assessing VTE components, AD was associated with a higher risk of DVT (aHR 1.30, 95% CI 1.23–1.37) but not PE (aHR 0.94, 95% CI 0.87–1.02). The VTE risk was greater in older people with AD (≥ 65 years: aHR 1.22, 95% CI 1.15–1.29; 45–65 years: aHR 1.15, 95% CI 1.05–1.26; < 45 years: aHR 1.07, 95% CI 0.97–1.19) and those with obesity [body mass index (BMI) ≥ 30: aHR 1.25, 95% CI 1.12–1.39; BMI < 30: aHR 1.08, 95% CI 1.01–1.15). Risk was broadly consistent across mild, moderate or severe AD. Conclusions AD is associated with a small increase in risk of VTE and DVT, with no increase in risk of PE. The magnitude of this risk increase is modest in younger people, and those without obesity. [ABSTRACT FROM AUTHOR]

Tralokinumab is an anti-interleukin-13 monoclonal antibody approved in several geographical regions for the treatment of moderate-to-severe atopic dermatitis. This manuscript presents three case studies of patients with moderate-to-severe atopic dermatitis who had failed on prior treatments and took part in trials of tralokinumab. Data is available for approximately two years in each patient and indicates that treatment with tralokinumab every two weeks was associated with substantial improvements in patient itch, sleep and quality of life, with feedback from the patients suggesting that this had a meaningful impact on their daily lives. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is associated with immunological dysfunction, which may influence cancer development. Previous studies of AD and cancer demonstrate inconsistent results and few of these studies examined children or AD severity and treatment. Objectives To determine malignancy risk among children and adults with AD. Methods We conducted a cohort study using electronic health records data from UK general practices in The Health Improvement Network between 1994 and 2015. Children (< 18 years old) and adults (≥ 18 years old) with AD were matched on age, practice and index date to patients without AD. AD was categorized as mild, moderate or severe using treatments and dermatology referrals as proxies. The primary outcome was any incident malignancy, including in situ malignancy, identified using diagnosis codes and categorized into haematological, skin and solid organ malignancies. Secondary outcomes included specific malignancies: leukaemia, lymphoma, melanoma, nonmelanoma skin cancer (NMSC) and common solid-organ cancers. Results Among 409 431 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) and 1 809 029 children without AD who had median follow-up of 5–7 years, the incidence rates of malignancy were 1.9–3.4 and 2.0 per 10 000 person-years (PY), respectively. The adjusted risk of malignancy overall did not differ with respect to AD [hazard ratio (HR) 1.02 (95% confidence interval 0.92–1.12)]. Severe AD was associated with increased lymphoma risk [HR 3.18 (1.41–7.16), excluding cutaneous T-cell lymphoma (CTCL)], and mild AD was associated with increased NMSC risk [1.55 (1.06–2.27)]. Among 625 083 adults with AD (65.7% mild, 31.4% moderate, 2.9% severe) and 2 678 888 adults without AD who had median follow-up of 5 years, incidence rates of malignancy were 97.4–125.3 per 10 000 PY and 103.7 per 10 000 PY, respectively. The adjusted risk of any malignancy did not differ with respect to AD [HR 1.00 (0.99–1.02)]. However, adults with severe AD had a twofold higher risk of non-CTCL lymphoma. AD was also associated with slightly higher skin cancer risk [HR 1.06 (1.04–1.08)] and slightly lower solid cancer risk [0.97 (0.96–0.98)] but results varied by specific cancers and AD severity. Conclusions Epidemiological evidence does not support a strong overall malignancy risk in AD but lymphoma risk may be increased with severe AD. [ABSTRACT FROM AUTHOR]

From dry skin in the newborn to atopic eczema in the infant and child, health professionals in primary care play a crucial role in supporting families in the care of skin, and the treatment and management of skin conditions in children. The evidence base can be conflicting and guidance changes frequently. With so much information to share with new parents, baby skincare is often seen as a lower priority when imparting health promotion advice than other areas such as safe sleep or infant feeding. It has been argued that, with the rising prevalence of atopic eczema in the UK population, advice to parents about what to be concerned about and when to seek medical advice is imperative. This article explores the evidence on general skincare from the newborn period to the treatment and management of common skin conditions, including atopic eczema and seborrheic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia. Objective: To determine if AE is associated with lymphopenia. Methods: We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997–2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]). Results: Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09–1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference −0.047 × 109/L [95% CI: −0.051 to −0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80–2.11), and the adjusted mean lymphocyte count difference was −0.03 × 109/L (95% CI: −0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections. Conclusion: Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded. Objectives: Our study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect. Methods: Two-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses. Results: Genetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P<0.001), type 1 diabetes (OR, 1.37; P=0.0084) (ORMVMR1, 1.42; P=0.0155) (ORMVMR2, 1.45; P=0.002), and alopecia areata (OR, 1.98; P=0.0059) (ORMVMR1, 2.55; P<0.001) (ORMVMR2, 1.99; P=0.003) in both univariable and multivariable MR. These causal relationships were supported by sensitivity analyses. No causal effect of AD was identified in relation to systemic lupus erythematosus, vitiligo, and ankylosing spondylitis. Concerning the reverse directions, no significant association was noted. Conclusion: The results of this MR study provide evidence to support the idea that AD causes a greater risk of rheumatoid arthritis, type 1 diabetes and alopecia areata. Further replication in larger samples is needed to validate our findings, and experimental studies are needed to explore the underlying mechanisms of these causal effects. [ABSTRACT FROM AUTHOR]

Background: Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI – ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults. Methods: We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥ 18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis. Results: We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12– 1.22; psoriasis: HR=1.26,95% CI=1.18– 1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93– 1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05– 1.23). Conclusion: Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis. [ABSTRACT FROM AUTHOR]

We explored patient satisfaction with baricitinib, an oral Janus kinase inhibitor, in patients with atopic dermatitis (AD) treated in routine clinical practice. Adults with moderate-to-severe AD treated with baricitinib in clinical practice for ≥4 weeks in France, Germany, and the UK completed a one-time online survey under market research methodologies. Treatment satisfaction was assessed using a Likert scale and abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9). Patients reported demographic, disease, and treatment information. Data were analyzed descriptively. The survey was completed by 170 patients with a mean age of 39.3 years (SD = 13.5), 59% (n = 101) were female. At baricitinib initiation, 79% rated their AD as "Severe", yet 28% reported body surface area (BSA) involvement ≥10%. Most were "Satisfied" or "Very satisfied" (76%/18%) with baricitinib, with high rates reported for controlling itch (36%/56%). Itch improvements were noted by 97% of patients. Some tapered/stopped (50%/32%) topical corticosteroid use, aligned with reported improvements on the patient global assessment and BSA. Mean TSQM-9 convenience score was 78.0 (SD = 14.0). Satisfaction with itch control was particularly high, reflected in rates of improvement in itch since starting baricitinib. On the TSQM-9, the convenience score was the highest. Many patients tapered/stopped concomitant topicals, indicating baricitinib's effect in controlling AD symptoms. [ABSTRACT FROM AUTHOR]

Dupilumab is prescribed in one dosage across adult atopic dermatitis patients. Differences in drug exposure may explain variation in treatment response. Investigating the clinical relevance of dupilumab serum concentration in atopic dermatitis in real-world practice. In two centers (Netherlands, UK), adults treated with dupilumab for atopic dermatitis were evaluated for effectiveness and safety pretreatment and at 2, 12, 24, and 48 weeks; trough serum samples were analyzed for dupilumab concentration at corresponding time points. In 149 patients, median dupilumab levels during follow-up ranged from 57.4 to 72.4 μg/mL. Levels showed high inter-patient and low intra-patient variability. No correlation was found between levels and ΔEASI. At 2 weeks, levels of ≥64.1 μg/mL predict EASI ≤7 at 24 weeks (specificity:100%, sensitivity:60%; p =.022). At 12 weeks, ≤32.7 μg/mL predicts EASI >7 at 24 weeks (sensitivity:95%, specificity:26%; p =.011). Inverse correlations were found between baseline EASI and levels at 2, 12, and 24 weeks (r = −0.25 to 0.36; p ≤.023). Low levels were particularly observed in patients with adverse events, treatment interval deviation, and discontinuation. At the on-label dosage, the measured range of dupilumab levels does not seem to yield differences in treatment effectiveness. However, disease activity does seem to influence dupilumab levels - higher baseline disease activity results in lower levels at follow-up. [ABSTRACT FROM AUTHOR]

Background: Paediatric atopic dermatitis (AD) has been linked to neuropsychiatric comorbidities such as depression, anxiety and attention‐deficit/hyperactivity disorder (ADHD). However, longitudinal data are limited, and the effect of AD severity on neuropsychiatric outcomes requires further characterization. Objectives: To determine the risk of several major neuropsychiatric conditions in children with AD. Methods: We analysed UK health records data in a population‐based cohort study. Each patient <18 years old with AD was matched to up to five unaffected patients on age, practice and index date. Treatments served as proxies for AD severity, which was analysed in a time‐updated manner. Outcomes were incident anxiety, depression, bipolar disorder, schizophrenia, ADHD, autism, obsessive–compulsive disorder (OCD), suicidal ideation or attempt, and completed suicide. Results: A total of 409,431 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) were compared to 1,809,029 children without AD. In Cox regression models adjusted for age, sex, socioeconomic status and other atopic comorbidities, no statistically significant relationships were observed between AD and incident anxiety (HR 1.01, 95% CI 0.99–1.03), ADHD (1.02, 0.97–1.06), autism (1.02, 0.98–1.06), bipolar disorder (1.08, 0.85–1.36), suicidal ideation/attempt (0.98, 0.95–1.01) or completed suicide (0.85, 0.64–1.14). Children with AD were less likely to develop depression (0.93, 0.91–0.95) or schizophrenia (0.72, 0.54–0.95) but more likely to develop OCD (1.26, 1.16–1.37). However, there was substantial variation by AD severity and age in both the direction and magnitude of effect for many of the neuropsychiatric conditions examined. Conclusions: The was no substantial impact of AD on the overall risk of many neuropsychiatric conditions in children, but disease severity and age may be important modifying factors. Additional research is needed to further dissect the complex relationship between paediatric AD and neuropsychiatric comorbidities. [ABSTRACT FROM AUTHOR]

Keywords: atopic dermatitis; mental health; psychodermatology; quality of life EN atopic dermatitis mental health psychodermatology quality of life 113 117 5 01/27/23 20230101 NES 230101 Key messages Stress and Atopic Dermatitis severity significantly predict the quality of life in UK adults There are differences in Atopic Dermatitis severity and depression reported across different ethnicities. Therefore, when comparisons with healthy groups are not needed, measuring QoL in those with AD using an AD-specific QoL tool rather than a generic tool is recommended to help inform AD management. Physical QoL, social QoL, stress and AD severity were significantly associated with AD-specific QoL. AD severity was significantly associated with QoL after controlling for psychological factors, a finding consistent with a recent systematic review.[3] Stress, general physical and social QoL were also significantly associated with AD-specific QoL, after controlling for demographic and clinical variables. [Extracted from the article]

Introduction and aims Maternal influences on infantile atopic eczema are complex, with emerging evidence for a protective role for maternal T helper (Th)1 inflammation during pregnancy. Substantial literature on characterization of a proinflammatory dietary pattern, led us to hypothesize that analyses of maternal diet and markers of inflammation might help identify mechanisms influencing the risk of infantile atopic eczema. The aim of this study was to examine the associations between energy-adjusted dietary inflammatory index (eDII) scores indicative of a proinflammatory diet pattern, maternal serum neopterin levels (a biomarker elevated in Th1 immune activation which counteracts Th2 inflammation seen in atopic eczema), and infantile risk of atopic eczema. Methods Within the UK Southampton Women's Survey, scores for the eDII were derived from mothers' diets (questionnaires at preconception, early and late pregnancy). Atopic eczema was ascertained at age 6 and 12 months using the UK Working Party Diagnostic Criteria (n = 262 and 270, respectively). Late pregnancy maternal serum neopterin levels were measured in a subsample (n = 497). Directed acyclic graphs were used to determine covariates to be included in linear regression analyses. Results A higher eDII score in late pregnancy was associated with a reduced risk of atopic eczema at age 6 months [odd ratios (OR) 0.89, 95% CI confidence interval (CI) 0.81–0.98; P = 0.02], with a similar trend at age 12 months (OR 0.91, 95% CI 0.83–1.00; P = 0.06). Consistent with this, and adjusting for maternal body mass index, education, smoking during pregnancy, and recent eczema, and infant filaggrin single-nucleotide polymorphism rs7512552, breastfeeding duration and sex, higher maternal serum concentrations of neopterin were associated with lower risks of infant eczema at age 6 months (OR 0.72, 95% CI 0.51–1.01; P = 0.05) and 12 months (OR 0.71, 95% CI 0.53–0.96; P = 0.03). Conclusions These findings suggest that a proinflammatory maternal diet that promotes a Th1 predominant environment protects the developing infant from Th2 inflammation and reduces the risk of atopic eczema. [ABSTRACT FROM AUTHOR]

The mutational spectrum of asthma and allergy associated genes is not known although recent biobank based exome sequencing studies included these traits. We therefore conducted a secondary analysis of exome data from 281,104 UK Biobank samples for association of mostly rare variants with asthma, allergic rhinitis and atopic dermatitis. Variants of interest (VOI) were tabulated, shared genes annotated and compared to earlier genome-wide SNP association studies (GWAS), whole genome sequencing, exome and bisulfit sequencing studies. 354 VOI were significantly associated with asthma, allergic rhinitis and atopic dermatitis. They cluster mainly in two large regions on chromosome 6 and 17. After exclusion of the variants associated with atopic dermatitis and redundant variants, 321 unique VOI remain in 122 unique genes. 30 genes are shared among the 87 genes with increased and the 65 genes with decreased risk for allergic disease. 85% of genes identified earlier by common GWAS SNPs are not replicated here. Most identified genes are located in interferon ɣ and IL33 signaling pathway. These genes include already known but also new pharmacological targets, including the IL33 receptor ST2/IL1RL1, as well as TLR1, ALOX15, GSDMA, BTNL2, IL13 and IKZF3. Future pharmacological studies will need to included these VOI for stratification of the study population paving the way to individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Recap of atopic eczema (RECAP) is a patient‐reported outcome measure assessing eczema control. This instrument has been developed and validated in the UK. There are self‐reported and proxy‐reported versions in English, Dutch and German. However, it is unclear whether the self‐reported version shows adequate content validity when completed by young people (8–16 years) in these languages. Objectives: To assess the content validity (comprehensibility, relevance and comprehensiveness) of the English, German and Dutch versions of the self‐reported RECAP in young people with atopic eczema and to identify the most appropriate age cutoff for self‐completion. Methods: We conducted 23 semistructured cognitive interviews with young people aged 8–16 years, using the 'think‐aloud' method. In Germany and the Netherlands, participants were recruited in dermatology clinics and in the UK through social media and existing mailing lists. Interviews were audio recorded, transcribed verbatim and analysed in the three languages, using a problem‐focused coding manual. Transcripts were coded by two independent reviewers in each country. Themes were translated into English and compared across the three countries. Results: Significant age‐related comprehensibility issues with the last three items of the questionnaire occurred with young people aged 8–11 years, causing difficulties completing RECAP without help. However, older children had only minor problems and were able to complete the questionnaire by themselves. The self‐reported version of RECAP has sufficient content validity for self‐completion in young people aged 12 years and above. However, the German version with some translational adaptations may be appropriate for children from the age of 8 years. There may be some situations where the proxy version is needed for older children too. Conclusions: The self‐reported version of RECAP is appropriate for use from the age of 12 years. The proxy version can be used in children younger than 12 years. Other measurement properties should be further investigated. What is already known about this topic?Recap of atopic eczema (RECAP) is an instrument recommended by the Harmonising Outcome Measures for Eczema initiative for the core outcome domain of long‐term control of atopic eczema.Content validity of RECAP for self‐completion by adults and of the proxy version has been assessed. What does this study add?In this study, content validity (comprehensibility, relevance and comprehensiveness) of the self‐reported version of RECAP among young people (aged 8–16 years) with atopic eczema across the UK, Germany and the Netherlands is assessed.Based on these findings, key recommendations on how to measure eczema control in young people with atopic eczema are formulated. What are the clinical implications of this work?The Dutch, English and German self‐completion versions of RECAP are recommended for use in adolescents from the age of 12 years.The proxy version could be used in children younger than 12 years or where children are cognitively or physically incapable of reporting their experience of eczema control.Caregivers should be encouraged to complete RECAP together with their child where possible. [ABSTRACT FROM AUTHOR]

The expanding number of potential treatment options for atopic dermatitis (AD) highlights the need to better understand the treatment preferences of individuals with AD. This study identified attributes that most greatly influenced treatment preferences of adults/adolescents/caregivers of children with mild/moderate/severe AD. Adults (≥18 years), adolescents (12–17 years), and caregivers of children (2–11 years) with mild, moderate, or severe AD in the United States (US) and United Kingdom (UK) participated in semistructured interviews. Thematic analysis was used to identify and generate themes across the interview results describing the treatment attributes of greatest importance to participants. Qualitative interviews were conducted with 35 adults, 35 caregivers, and 33 adolescent participants across both countries (n = 103; US = 51; UK = 52) and all severity groups (mild = 43; moderate = 47; severe = 13). The most important treatment attributes included efficacy (96.1%; speed and duration of symptom relief), mode of administration (66.0%; route of administration, frequency, and convenience), and side effects (55.3%, short-term, long-term, and general). Efficacy, mode of administration, and side effects were the most important attributes that influenced AD treatment preferences for patients and caregivers across different countries, ages, and disease severity. These results may assist patients/caregivers/clinicians in shared decision-making discussions to improve treatment adherence and outcomes. [ABSTRACT FROM AUTHOR]

Background: Eczema affects one in five children in the UK. Regular application of emollients is routinely recommended for children with eczema. There are four main emollient types, but no clear evidence of which is best. The current 'trial and error' approach to find suitable emollients can be frustrating for parents, children, and clinicians.Aim: To identify how parents and children experience and evaluate emollients.Design and Setting: Qualitative interview study, nested within a primary care trial of emollients (Best Emollients for Eczema [BEE] trial).Method: Semi-structured interviews with children with eczema and their parents were conducted. Participants were purposively sampled on emollient type (lotion, cream, gel, or ointment), age, and eczema severity.Results: Forty-four parents were interviewed, with children participating in 24 of those interviews. There was no clear preference for any one emollient type. The strongest theme was the variation of experience in each of the four types. Participants focused on thickness and absorbency, both positively and negatively, to frame their evaluations. Effectiveness and acceptability were both considered when evaluating an emollient but effectiveness was the primary driver for continued use. For some, participating in the trial had changed their knowledge and behaviour of emollients, resulting in use that was more regular and for a longer duration.Conclusion: There is no one emollient that is suitable for everyone, and parents/children prioritise different aspects of emollients. Future research could evaluate decision aids and/or tester pots of different types, which could enable clinicians and parents/children to work collaboratively to identify the best emollient for them. [ABSTRACT FROM AUTHOR]

Summary: Background: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. Objectives: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. Methods: A randomized observer‐blind intrapatient‐controlled study in 34 adults with dry, eczema‐prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier‐transform infrared spectroscopy using a novel interface. Results: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve −162, 95% confidence interval (CI) −206 to −118]. Skin sensitivity to sodium lauryl sulfate was reduced (−0·5 points visual redness, 97·57% CI −1·00 to −0·25), as was transepidermal water loss (−15·3 g m−2 h−1, 95% CI −20·3 to −10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61–10·6) and decreased signs of dryness. Conclusions: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin. [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]

Summary: Background: Staphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections. Objectives: To determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD. Methods: We conducted a population‐based cohort study using UK‐based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein–Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections. Results: Among 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50–52% greater risk of HSV and 18–33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38–4·54] and adults with severe AD (HR 4·45, 95% CI 1·76–11·25). Patients with AD had a 26–40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20–1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD. Conclusions: AD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose‐dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications. Whatis already known about this topic?Atopic dermatitis (AD) is associated with infectious complications, most commonly staphylococcal and herpes simplex virus infections.However, the risk of serious infections, opportunistic infections and other herpesvirus infections in patients with AD has not been fully characterized. Whatdoes this study add?AD is associated with an increased risk of hospitalized infections, opportunistic infections and several herpesvirus infections in both children and adults, with risk being greatest among those with severe skin disease.The elevated risks of these infections appear independent of immunosuppressive medication use for AD. Linked Comment:N. Novak and B. Cabanillas. Br J Dermatol 2022; 186:604–605. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Diagnosing atopic dermatitis (AD) in infants is challenging. Objectives: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. Methods: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. Results: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22–0·48] or 12 months (OR 0·49, 95% CI 0·32–0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3–43·6) or two (OR 6·5, 95% CI 4·3–9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. Conclusions: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings. What is already known about this topic? Eczema is common in infants, while the proportion of infants with clinical eczema having atopic dermatitis (AD) is uncertain.Criteria‐based AD in infants increases the risk of developing allergic comorbidities, and an early appearance of AD may indicate a more severe disease phenotype.Studies determining AD with the UK Working Party and Hanifin and Rajka criteria in the first year of life are largely lacking. What does this study add? Of 34% of infants with eczema, one‐third fulfilled the diagnostic criteria for AD.Infants with eczema at 3 months vs. later in life, or with eczema at more than one visit, were most likely to fulfil the diagnostic AD criteria.Except for clinical research, the present diagnostic criteria for AD may have limited clinical value in infants. Linked Comment: Z. Chiesa. Br J Dermatol 2022; 186:6. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Palmar hyperlinearity is a feature of ichthyosis vulgaris, the monogenic skin disorder caused by FLG loss‐of‐function mutations. Objective: To investigate how well the presence or absence of hyperlinear palms (HLP) detect FLG genotype in children. Methods: STARD criteria are used to report this diagnostic accuracy study. Phenotype and genotype data (four most prevalent FLG null mutations) were obtained from a total of 3656 children in three studies: the UK CLOTHES trial (children 1–5 years with moderate–severe atopic eczema); UK BEEP trial (2 year olds at high risk of developing atopic eczema); UK‐Irish eczema case collection (0–16 year olds with atopic eczema). All participants included in analyses of HLP as the index test and FLG genotype as the reference were of white European ancestry. Results: Thirty‐two percent of participants (1159/3656) had FLG null mutation(s) and 37% (1347/3656) had HLP. In 13% (464/3656), HLP was recorded as 'unsure' or not recorded. The sensitivity and specificity of HLP for detecting FLG mutations in each of the studies was: 67% (95% CI 55–78%) and 75% (67–82%) in CLOTHES; 46% (36–55%) and 89% (86–91%) in BEEP; 72% (68–75%) and 60% (57–62%) in the UK‐Irish case collection. Positive and negative likelihood ratios were: 2.73 (1.95–3.81) and 0.44 (0.31–0.62) in CLOTHES; 4.02 (2.99–5.40) and 0.61 (0.52–0.73) in BEEP; 1.79 (1.66–1.93) and 0.47 (0.42–0.53) in the UK‐Irish collection. Discussion: Trained observers were able to define palmar hyperlinearity in the majority (3191/3656, 87%) of cases. The presence of HLP is not a reliable sign to detect FLG mutations, but the absence of HLP excludes FLG null genotype with a reasonable degree of certainty. [ABSTRACT FROM AUTHOR]

Background: Observational studies have reported an association between allergic disease and mental health, but a causal relationship has not been established. Here, we use Mendelian randomization (MR) to investigate a possible causal relationship between atopic disease and mental health phenotypes. Methods: The observational relationship between allergic disease and mental health was investigated in UK Biobank. The direction of causality was investigated with bidirectional two‐sample MR using summary‐level data from published genome‐wide association studies. A genetic instrument was derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. We also investigated whether these relationships were specific to atopic dermatitis (AD), asthma or hayfever. Given the multiple testing burden, we applied a Bonferroni correction to use an individual test p‐value threshold of.0016 (32 tests). Results: We found strong evidence of an observational association between the broad allergic disease phenotype and depression (ORself‐report=1.45, 95% CI: 1.41–1.50, p = 3.6 × 10−130), anxiety (OR=1.25, 95% CI: 1.18–1.33, p = 6.5 × 10−13), bipolar disorder (ORself‐report=1.29, 95% CI: 1.12–1.47, p = 2.8 × 10−4) and neuroticism (β = 0.38, 95% CI: 0.36–0.41, p = 6.8 × 10−166). Similar associations were found between asthma, AD, hayfever individually with the mental health phenotypes, although the associations between AD and hayfever with bipolar disorder were weaker. There was little evidence of causality in either direction (all p‐values>.02). Conclusion: Using MR, we were unable to replicate most of the phenotypic associations between allergic disease and mental health. Any causal effects we detected were considerably attenuated compared with the phenotypic association. This suggests that most comorbidity observed clinically is unlikely to be causal. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults. Objective: To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort. Methods: This was a cohort study of 9,154,936 individuals aged 0–99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0–17 years), adults (18–74 years), and older adults (75–99 years). Results: Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70–0.76) and was more likely to be active (59.7%, 95% CI 59.5–59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups. Conclusion: In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0–17 and adults ages 18–74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. Objectives: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. Methods: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. Results: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe–Frequent (4%), Moderate–Frequent (7%), Moderate–Declining (11%) and Mild–Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD‐PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD‐PRS further differentiated some phenotypes from each other. Conclusions: Considering severity and AD trajectories leads to four well‐defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research. What's already known about this topic? Atopic dermatitis (AD) is a heterogeneous condition in terms of both disease activity and severity.Childhood AD phenotypes in previous studies have focused only on disease activity. What does this study add? We incorporate disease severity over time to derive four clinically recognizable AD phenotypes using data‐driven methods.Disease severity improved over time in all phenotypes (even in those with high probability of activity in late childhood and adolescence).Several established risk factors, including genetic associates, were associated with our proposed phenotypes, with most factors more strongly associated with phenotypes reporting the worst symptoms. Fewer factors differentiated between more Frequent and Declining/Intermittent phenotypes. Linked Comment: C. Vestergaard. Br J Dermatol 2021; 185:477. [ABSTRACT FROM AUTHOR]

Introduction: The burden of mild-to-moderate atopic dermatitis (AD) in the United Kingdom (UK) is not well understood. Long-lasting AD flares may lead to systemic inflammation resulting in reversible progression from mild to more severe AD. This study aimed to assess the clinical and economic burden of mild-to-moderate AD in the UK. Methods: AD patients were identified in the Health Improvement Network (THIN) from 2013 to 2017 and propensity score matched to non-AD controls by demographics. Patients were identified based on continuous disease activity using validated algorithms and sufficient patient status to fully validate data integrity for the entire period. Mild-to-moderate AD patients were identified by using treatment as a surrogate. Demographics, clinical characteristics and healthcare resource use (HCRU) were obtained from THIN. Literature reviews were conducted to obtain additional outcomes. A cost-of-illness model was developed to extrapolate the burden in 2017 to the UK population and in subsequent years (2018–2022). Results: In 2017, the prevalence of mild-to-moderate AD in THIN was 1.28%. These patients reported higher comorbidity rates and significantly higher (p < 0.0001) HCRU, encompassing mean general practitioner visits (5.57 versus 3.59), AD-related prescriptions (5.85 versus 0.68) and total referrals (0.97 versus 0.82) versus matched non-AD controls. The model projected total HCRU and drug excess costs of €462.99M over the 5 years. The excess cost decreased to €417.35M after excluding patients on very potent topical corticosteroids, who most likely had at least moderate disease. The excess costs increased to €1.21B and €7.06B when considering comorbidity burden and productivity losses, respectively. Conclusion: Mild-to-moderate AD patients had higher comorbidity burden, HCRU and cost compared with matched non-AD controls. Overall, UK country-based economic burden was high given partly the high prevalence of this disease. Moreover, productivity burden and comorbidities had considerable impact on the economic burden, which further suggests the importance of optimal disease management. [ABSTRACT FROM AUTHOR]

Keywords: asthma; atopic dermatitis; autoimmunity; epidemiology; ethnicity; rheumatoid; rhinitis; SLE; vitiligo EN asthma atopic dermatitis autoimmunity epidemiology ethnicity rheumatoid rhinitis SLE vitiligo 144 147 4 01/05/21 20210101 NES 210101 To the Editor, The burden of allergic diseases (ADs) such as asthma and rhinitis and autoimmune disorders (AIDs) such as rheumatoid arthritis (RA) is relatively low/moderate in low- and low-middle-income countries,1,2 and there is some evidence regarding higher incidence rates of these conditions amongst immigrant population settled in high-income countries.3,4 The burden of ADs is particularly high in high-income countries such as the UK, Republic of Ireland and New Zealand.1 Studies in immigrants have been limited by several factors including relatively small sample size, shorter duration and methodological issues such as selection bias, survey- or questionnaire-based data, focus on a single or limited number of ADs or AIDs, and some not accounting for important disease confounders such as smoking history. Specifically, the risk of AE, ARC, SLE, ATD and vitiligo is uniformly higher amongst British ethnic minority groups in comparison with the White population. Asthma, atopic dermatitis, autoimmunity, epidemiology, ethnicity, rheumatoid, rhinitis, SLE, vitiligo. [Extracted from the article]

Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin condition associated with a significant health-related and socioeconomic burden, and is characterized by intense itch, disruption of the skin barrier, and upregulation of type 2-mediated immune responses. The United Kingdom (UK) has a high prevalence of AD, affecting 11–20% of children and 5–10% of adults. Approximately 2% of all cases of childhood AD in the UK are severe. Despite this, most AD treatments are performed at home, with little contact with healthcare providers or services. Here, we discuss the course of AD, treatment practices, and unmet need in the UK. Although the underlying etiology of the disease is still emerging, AD is currently attributed to skin barrier dysfunction and altered inflammatory responses. Management of AD focuses on avoiding triggers, improving skin hydration, managing exacerbating factors, and reducing inflammation through topical and systemic immunosuppressants. However, there is a significant unmet need to improve the overall management of AD and help patients gain control of their disease through safe and effective treatments. Approaches that target individual inflammatory pathways (e.g. dupilumab, anti-interleukin (IL)-4 receptor α) are emerging and likely to provide further therapeutic opportunities for patient benefit. [ABSTRACT FROM AUTHOR]

Background: There is limited understanding on patterns of systemic treatment in adults with moderate-to-severe atopic dermatitis (AD) in the UK. Objective: To characterize treatment patterns in adult AD patients prescribed immunosuppressants (IMMs) in the primary care setting. Results: Six hundred and fifty-six patients with AD (6.6%) were prescribed IMM in the analysis (mean age 52.1 years; 59.1% female; age-adjusted Charlson comorbidity index 1.4). Most prevalent (>5%) conditions at baseline were depression (10.8%), contact dermatitis (10.7%), rheumatological disease (7.9%), skin/subcutaneous tissue disorders (6.4%), upper respiratory disease (5.8%), and psoriasis (5.2%). At baseline, up to 50% of patients were prescribed ≥1 IMM. During follow-up, 42.7% of patients were prescribed oral corticosteroids (OCSs), increasing in line with IMM exposure. The most commonly prescribed IMM was methotrexate (43.3%). Ciclosporin, the only approved IMM for AD, was prescribed to 16.9% of patients. Conclusions: The prevalence of comorbidities and high rate of IMM prescriptions demonstrate the impact of AD on quality of life. The frequency of OCS prescribing in AD patients treated with IMMs suggests a lack of disease control with existing therapies, and an unmet need for safe and effective targeted agents for long-term disease control. [ABSTRACT FROM AUTHOR]

• Asthma or atopic dermatitis were associated with increased risk of depression and anxiety. The association was stronger among participants on current therapy. • Participants reporting both asthma and atopic dermatitis presented the highest risk of depression and anxiety. • A dose-response association was observed between neutrophil-to-lymphocyte ratio with depression and anxiety. • A dose-response relationship was observed between Peak Expiratory Flow rate with depression and anxiety in asthma. • Middle-age onset asthma or atopic dermatitis presented the strongest associations with depression and anxiety. The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (β = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, β = 0.30, 95% CI, 0.27,0.34; tertile 2, β = 0.36, 95%CI, 0.32,0.39, and tertile 3, β = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40–59 age group (β = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (β = 0.43, 95%CI, 0.34,0.51 and 20–39 groups (β = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose–response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40–59) were associated with the highest increment in DAS. [ABSTRACT FROM AUTHOR]

Introduction: The replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids. Methods: A double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 μl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application). Results: The test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h. Conclusion: The sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3–4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. Objectives: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. Methods: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997–2017) and Danish nationwide registries (1997–2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta‐analysis. Results: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98–1·04) across the entire follow‐up. Similar results were found in other shorter follow‐up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84–1·12) across the entire follow‐up, 1·09 (95% CI 0·86–1·38) within 0–30 days, 1·18 (95% CI 1·04–1·35) within 0–90 days, 1·14 (95% CI 1·06–1·22) within 0–365 days and 1·07 (95% CI 1·02–1·12) within 0–1095 days. Conclusions: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long‐term risk of psoriasis and atopic eczema following bereavement. What's already known about this topic? Psychological stress is commonly cited as a risk factor for psoriasis and atopic eczema. However, clinical evidence supporting such associations is limited.Current epidemiological evidence for the relationship is limited by small sample sizes and difficulty measuring stress. What does this study add? In two population‐based cohort studies, there was no evidence of an increased risk of psoriasis associated with partner bereavement.There was a short‐term increased risk of atopic eczema in the 3 years following partner bereavement, which peaked during the first year. However, there was no evidence of an increased long‐term risk of atopic eczema.Acute stress may trigger onset or relapse of atopic eczema, leading to an increased risk of atopic eczema in the short term following partner bereavement. Linked Comment: von Kobyletzki. Br J Dermatol 2020; 183:207. Plain language summary available online [ABSTRACT FROM AUTHOR]

This document is a correction notice for two articles published in the British Journal of Dermatology. The correction clarifies that Sigrún Schmidt and Sinéad Langan are joint senior authors of the articles. The articles discuss the relationship between partner bereavement and the risk of psoriasis, atopic eczema, chronic urticaria, alopecia areata, and vitiligo. The studies were conducted in the UK and Denmark. The correction provides the correct information regarding the authors' status. [Extracted from the article]

Background: Alkyl glucosides contitute a family of mild surfactants that are increasingly being used in a wide range of cosmetics and household products. Contact allergy to alkyl glucosides may be more frequent than previously suspected, especially in atopic patients. Objectives: To investigate the frequency of contact allergy to alkyl glucosides, and to identify concomitant reactivity. Method: We retrospectively reviewed all cases of suspected allergic contact dermatitis (ACD) in which patients were patch tested with either a cosmetic series that includes five alkyl glucosides (decyl glucoside, lauryl glucoside, coco glucoside, cetearyl glucoside, and caprylyl/capryl glucoside) or a specific alkyl glucoside series from November 2013 to April 2017 in two UK centres. Results: A total of 5775 patients were patch tested across the two centres. Twenty‐nine (1.04%) of the 2796 patients tested with the cosmetic/alkyl glucoside series had a positive patch test reaction to at least one of the alkyl glucosides. Twenty‐three (79.3%) patients were sensitized to multiple alkyl glucosides; 21 patients (72.4%) were female. The mean age was 43.5 years. Twelve patients (41.4%) had a background of atopic dermatitis. Conclusions: The prevalence of alkyl glucoside‐induced ACD is relatively high, and there are frequent concomitant reactions between different alkyl glucosides. We recommend the inclusion of alkyl glucosides in all cosmetic series. [ABSTRACT FROM AUTHOR]

Epidermal proteases, such as human tissue kallikrein-related peptidase, regulate skin barrier function through keratinocyte desquamation, antimicrobial defence, inflammatory response and barrier maintenance. It has been reported that the activity of kallikreins (KLKs) is upregulated in inflammatory skin disorders, including atopic dermatitis (AD; eczema). AD is a very common, chronic and relapsing inflammatory skin disease affecting 15–20% of children in the UK. Studies have shown that enhanced KLK5 results in AD-like skin architecture with an impaired skin barrier function. In this study, we aimed to develop a potent and selective inhibitor that targets KLK5 and restores epidermal barrier dysfunction in AD. Nature-based sunflower trypsin inhibitor 1 (SFTI), a small, circular peptide exhibiting wide-ranging serine protease inhibition can be engineered and modified to become a potent inhibitor specific for tissue kallikreins; our previous study also indicated that it was able to permeate through the outermost layer to exert its inhibitory action on serine proteases. In this study, we wanted to develop a more potent and specific inhibitor of KLK5 based on a lead SFTI analogue ('analogue 6') that was previously developed by our research group. Computer modelling was employed to assess the structure and binding affinity between KLK5 and SFTI-1. Designed SFTI analogues were then synthesized using solid phase peptide synthesis. The inhibitory effect was evaluated by its half maximal inhibitory concentration (IC50) against KLK5 using a 7-amido-4-methylcoumarin assay and further tested by protease-activated receptor 2-dependent intracellular calcium influx assay in keratinocytes. Computer modelling then indicated that an endogenous inhibitor was comparable with the analogue 6 we developed previously. Analogue 6 was further modified, based on the endogenous inhibitor structure, and synthesized. The new analogue achieved an IC50 of 14 nmol L–1 for KLK5, which was a fourfold increase in potency compared to analogue 6 (IC50 56 nmol L–1) and a 16-fold increase vs. SFTI-1 wild type (IC50 230 nmol L–1). Further, the new analogue could inhibit proteinase-activated receptor 2 (PAR2)-dependent intracellular calcium influx by modulating the activation of PAR2 receptor, a KLK5 downstream molecule in keratinocytes at a minimum inhibitor-to-enzyme molar ratio of 1:1. The novel potent inhibitor for KLK5 could be a potential therapeutic intervention for AD and other inflammatory skin conditions with enhanced KLK5. [ABSTRACT FROM AUTHOR]

A retrospective case note analysis and telephone consultation of 79 children, discharged from our teaching hospital with varicella zoster virus infection between 2003 and 2010, was performed. The hypothesis was that children with atopic dermatitis were more at risk of skin complications than children without. It was found that children with atopic dermatitis were significantly more likely to have varicella zoster virus infection complicated by cellulitis (21% versus 6%; p=0.05), haemorrhagic varicella (14% versus 2%; p=0.04) and superimposed 'skin and soft tissue infection' (61% versus 34%; p=0.008). Subjective severity of scarring was scored significantly higher in children with atopic dermatitis compared to those without (p = 0.006). In conclusion, skin related complications of varicella zoster virus infection are significantly more common in children with atopic dermatitis. Inclusion of atopic dermatitis as a "special case" in childhood vaccination programmes may prevent these complications. This warrants further more objective evaluation in a prospective study. [ABSTRACT FROM AUTHOR]

BackgroundThere are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood.MethodParticipants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361).ResultsAfter adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10–2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose–response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03–2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood.ConclusionsHigher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder. [ABSTRACT FROM PUBLISHER]