Anne‐Sofie Halling

Background: Atopic dermatitis (AD) is driven by a complex interplay of skin barrier dysfunction and immune dysregulation, including a significant T‐cell–mediated immune response. The thymus is the key organ of T cell receptor gene rearrangement and T‐cell maturation in early life. This study investigated whether infant thymus size is associated with incident AD during the first 2 years of life.Methods: Three hundred term newborns were followed clinically from birth until 2 years of age. Trans‐sternal ultrasound scans of the thymus were performed at birth, 2 months, and 12 months. The thymic index was calculated and dichotomized at ≥ 90th percentile. Skin tape strips from the dorsal hand were analyzed for immune biomarkers. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for AD risk and early‐onset AD. Multivariate analyses (aHR) were adjusted for sex, weight, height, breastfeeding, FLG mutation, and parental atopy.Results: Of the 300 enrolled children, 290 (97%) were eligible for analyses. The 2‐year cumulative prevalence of AD was 34.1% (95% CI: 28.7%–39.6%). A higher thymic index at 2 months was associated with increased AD risk during the first 2 years of life (HR: 3.51; 95% CI: [1.73–7.12]; p < 0.001), (aHR: 6.32; 95% CI: [2.81–14.20]; p < 0.001) and increased early‐onset AD before 6 months (HR: 2.95; 95% CI: [1.29–6.76]; p = 0.01), (aHR: 5.35; 95% CI: [2.05–13.90]; p < 0.001). A moderate correlation between thymic index and EASI (Eczema Area and Severity Index) was observed at 2 months of age (r = 0.39).Conclusion: Our findings indicate that increased thymic activity and T‐cell development may be associated with a higher risk of AD onset, suggesting a potential role of early‐life T‐cell maturation in disease pathogenesis.

Background Pediatric atopic dermatitis (AD) is closely linked to the subsequent development of food allergy, asthma, and rhinitis. It is currently unknown if the association is influenced by birth maturity. Objectives To investigate the occurrence of AD, food allergy, asthma, and rhinitis in term and preterm children from birth to age 4-5 years. Methods A prospective birth cohort of 389 children (261 term, 128 preterm) was followed from birth to 4–5 years. Results The overall prevalence of AD was 29.6% at age 2 years and 33.0% at 4-5 years. Preterm children had a lower prevalence of AD (19.2% vs. 39.8%, p < 0.0001), later AD onset (median 12.0 vs. 7.5 months, p < 0.01), milder disease severity (median EASI 1.4 vs. 4.8, p < 0.01), and less persistent AD (11.5% vs. 19.9%, p < 0.0001) than term children. Among children born preterm and term, the prevalence of food allergy, asthma, and rhinitis at ages 4-5 years was 1.6% vs. 3.1%, 20.0% vs. 13.0%, and 6.2% vs. 4.6%, respectively. No preterm children with AD (n=25) developed food allergies within 4–5 years compared to 6.7% among term born children, whereas asthma prevalence was higher among preterm children with AD (36.0%) compared to term children with AD (17.3%) (p=0.05). Conclusion Prematurely born children have a conspicuously reduced risk of AD, with later onset and a milder and less persistent disease course. Prematurely born children had significantly different epidemiology of food allergy and asthma compared to term born children.

Background: Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema ( AE ). We aimed to investigate gene–environment interactions (G × E) to improve understanding of the pathophysiology. Methods: We analysed data from 16 European studies to test for interaction between the 24 most significant AE‐associated loci identified from genome‐wide association studies and 18 early‐life environmental factors. We tested for replication using a further 10 studies and in vitro modeling to independently assess findings. Results: The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction ( p < 0.05) between seven environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R ) was nominally significant (OR _interaction = 0.91 [0.83–0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (OR _interaction = 0.84 [0.75–0.94] p = 0.003), but replication analysis was under‐powered (OR _interaction = 1.09 [0.82–1.46]). rs10214237 homozygous risk genotype is associated with lower IL‐7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. Conclusion: Interaction analysis and functional assessment provide preliminary evidence that early‐life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R , supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur.

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co‐occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta‐analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge‐proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full‐text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7–53.2), 32.7% (28.8–36.6) and 40.7% (34.1–47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3–56.2), 45.3% (41.4–49.3) and 54.9% (47.0–62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4–55.1)) and FA (31.4% (26.9–36.1)) prevalences than adults with AD (28.6% (13.4–46.8) and 24.1% (12.1–38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.

Accurate assessments of the burden of hand eczema (HE) in the general population are important for public awareness and intervention. The aim of this systematic review and meta‐analysis was to provide updated estimates of prevalence and incidence, alongside additional epidemiological endpoints on HE in the general population. PubMed, Embase and Web of Science were searched for studies reporting the prevalence and/or incidence of HE in the general population. Proportion meta‐analyses were performed to calculate pooled estimates of prevalence, incidence, severity, and the proportion of individuals with HE and a history of atopic dermatitis. Sixty‐six studies were included in the quantitative analysis encompassing 568 100 individuals. The pooled estimates for lifetime, 1‐year, and point prevalence were 14.5% (95% confidence interval [CI]: 12.6–16.5), 9.1% (95% CI: 8.4–9.8) and 4.0% (95% CI: 2.6–5.7), respectively. The pooled incidence rate of HE was 7.3 cases/1000 person‐years (95% CI: 5.4–9.5). The occurrence of HE was 1.5–2 times higher in females than males. More than one third suffered from moderate/severe disease and around one third had a history of atopic dermatitis. HE was a recurrent, long‐lasting disease with an average age at onset of the early‐ to mid‐twenties. In conclusion; HE is a highly prevalent disease in the general population and carries a significant risk of long‐term or chronic disease.