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Background: Atopic dermatitis (AD) is thought to precede the onset of other allergic illness (OAI) in a temporal progression (ie, atopic march), yet the timing and progression has been questioned. It is also unclear how parental allergic illness impacts the development of these illnesses in offspring., Objective: (1) Explore risk of incident AD and (2) timing of allergic disease onset in children of mothers with AD compared with mothers without AD from the United Kingdom., Methods: We created a birth cohort of mother-child pairs using IQVIA Medical Research Data database and developed Cox proportional models to examine the above associations (hazard ratio, HR [95% confidence interval, CI])., Results: Among 1,224,243 child-mother pairs, mean child (standard deviation) follow-up time was 10.8 (8.3) years and 50.1% were males (N = 600,905). Children were 59% (HR = 1.59 [1.57, 1.60]) more likely to have AD if their mothers had AD compared with no AD with mean age of first AD diagnosis at 3.3 (4.8) years. Most children with any diagnosis of AD present with AD first (91.0%); however, in those with asthma, only 67.8% developed AD first., Conclusion: Children born to mothers with AD are more prone to develop AD and some develop OAI first, suggesting that not all follow the same sequential pathway., Competing Interests: Conflicts of interest Dr Margolis is or recently has been a consultant for Pfizer, Leo, and Sanofi with respect to studies of atopic dermatitis and served on an advisory board for the National Eczema Association. Dr Chiesa Fuxench has received research grants from Lilly, LEO Pharma, Regeneron, Sanofi, Tioga, and Vanda for work related to atopic dermatitis and from Menlo Therapeutics and Galderma for work related to prurigo nodularis, has served as consultant for the Asthma and Allergy Foundation of America, National Eczema Association, AbbVie, Incyte Corporation, and Pfizer, and received honoraria for CME work in Atopic Dermatitis sponsored by education grants from Regeneron/Sanofi and Pfizer and from Beiersdorf for work related to skin cancer and sun protection. Drs Mitra and Shin and Authors Pozo and Hoffstad have no conflicts of interest to declare., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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]

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: 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]

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]

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]

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]

All publications covering diet during pregnancy that stemmed from the Avon Longitudinal Study of Parents and Children were reviewed. Diet was assessed using a food frequency questionnaire. Socioeconomic background, maternal mental health, and the health and development of the offspring were assessed using a variety of methods, such as direct measurement, self-completion questionnaires, and assays of biological samples. Differences in diet, including specific food and nutrient intakes and dietary patterns, were associated with maternal educational attainment, smoking habits, and financial difficulty. There were marginal intakes, compared with recommendations, of the key nutrients iron, magnesium, potassium, and folate. Maternal diet during pregnancy was predictive of offspring diet during childhood. There were independent associations between prenatal fish consumption and lower frequency of maternal depressive and anxiety symptoms, as well as lower frequency of intrauterine growth retardation. Consistent evidence that fish consumption during pregnancy benefited the neurocognitive development of the child was also found. Two constituents of fish, n-3 polyunsaturated fatty acids and iodine, were associated with these benefits in children. The findings from the Avon Longitudinal Study of Parents and Children strengthen the recommendation to eat fish regularly during pregnancy. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) is a chronic inflammatory skin disease with a large impact on quality of life of the patients and their families. In most cases, the diagnosis of AD can easily be made based on (family) history and clinical examination. If necessary, a practical set of diagnostic criteria such as the UK diagnostic criteria can be used. During the diagnostic phase, it is important to pay attention to atopic comorbidity, such as allergic airway disease (allergic asthma and/or rhinitis), allergic eye disease (atopic (kerato) conjunctivitis) and immediate-type food allergy. This will not have direct consequences for the treatment of AD, but may be important for the overall well-being of the patient. Psychological factors, such as family circumstances, work/school performance and lifestyle factors should also be explored. Severity scoring using properly validated scoring lists may not be necessary for the diagnosis, however, is recommended for monitoring therapy. Simple scoring systems, such as TIS and IGA are easy to perform in daily practice. Several flare factors in AD, such as exposure to irritants or UV light, can be identified by history and clinical examination: in individual cases, additional diagnostic tests may sometimes be useful to confirm clinical suspicion. There is only limited evidence that allergen exposure to aeroallergens and/or food allergens influences AD severity. Therefore, routine allergen testing is not necessary for diagnosis and treatment of AD. The decision to perform allergen tests mainly depends on atopic comorbidity. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) has been increasing in prevalence over the past few decades; however, AD has never been analyzed using a bibliometric approach. We searched for AD studies in the dermatology and allergy category of the Web of Science and SCOPUS databases using the keywords "atopic dermatitis", "eczema", and "atopy". In total, 53,460 documents were retrieved. We analyzed annual publication trends and performed keyword and co-authorship network analyses. The annual number of AD publications has increased over the years. Asthma, food allergies, the skin barrier, IgE, and epidemiology have received extensive attention. The keywords 'allergic rhinitis', 'child(ren)', 'quality of life', and 'probiotics' have become more commonly used in recent years. AD research has been led by only a few countries, such as the USA, Germany, and the UK, and longstanding research topics such as asthma, allergy, and the immune system continue to be important. We suggest that global collaborations, research in developing countries, and research that is more holistic (thus exploring how genes, the immune system, the environment, and the microbiome together impact AD) are necessary. [ABSTRACT FROM AUTHOR]

Since about 1960, the prevalence of asthma and allergic disease has increased sufficiently to become a major public-health concern. Concurrently, there have been marked changes in our diet, and it has been proposed that these changes have contributed to the increase in the prevalence of asthma and allergy. In this article, these hypotheses about diet are described, together with the postulated mechanisms and the evidence for and against, leading to the most recent evidence indicating that maternal diet during pregnancy might be particularly important in the development of childhood asthma. [ABSTRACT FROM AUTHOR]

The article offers tips on how to improve the management of atopic eczema in primary care. It discusses the diagnostic criteria developed by Great Britain's Working Party for atopic eczema, which include the history of involvement of the skin creases, personal history of asthma or hay fever and a history of generally dry skin. Treatment options include emollients, topical corticosteroids, and topical calcineurin inhibitors.

Background: There are currently limited data regarding the epidemiology of anaphylaxis. Objective: To estimate the incidence of anaphylaxis from all causes, to explore the variety of diagnoses that may predispose to an anaphylactic episode, and to estimate the rate of recurrence of anaphylaxis in patients with no asthma, nonsevere asthma, and severe asthma. Methods: The Health Improvement Network database provided data on individuals 10 to 79 years old who had been enrolled for at least 1 year with a general practitioner in the United Kingdom and had at least 1 health contact in the year before entering the study. Results: Anaphylaxis incidence rates (per 100,000 person-years) were 21.28 (95% CI, 17.64-25.44) and 50.45 (95% CI, 44.67-56.76) in the no asthma and overall asthma cohorts, respectively. Risk of anaphylaxis was greater in the nonsevere asthma (relative risk, 2.07; 95% CI, 1.65-2.60) and severe asthma (relative risk, 3.29; 95% CI, 2.47-3.47) subgroups compared with the no asthma cohort. The incidence rate of anaphylaxis was higher in women than men (22.65 vs 19.56 per 100,000 person-years). Within the overall asthma population, patients at significantly increased risk of anaphylaxis included those with allergic rhinitis or atopic dermatitis, and current users of antihistamines, oral steroids, or antibiotics (compared with nonusers). Drug and food allergies were the most common known causes of anaphylaxis. Conclusion: Patients with asthma have a greater risk of anaphylaxis than those without asthma, and the risk is greater in severe than nonsevere asthma. Women are at higher risk of anaphylaxis than men, especially those with severe asthma. [Copyright &y& Elsevier]