Skin TARC/CCL17 increase precedes the development of childhood atopic dermatitis.

BACKGROUND: It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk. OBJECTIVES: This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life. METHODS: This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD. RESULTS: The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection. CONCLUSIONS: This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.

Symptom burden of atopic dermatitis in early childhood assessed from daily monitoring of symptoms and topical steroid use.

BACKGROUND: To our knowledge, disease burden of atopic dermatitis (AD) as number of days with symptoms and medical treatment has never been studied as measure of severity. OBJECTIVES: To investigate risk factors for AD burden in the first 3 years of life. METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2010 included 700 children. AD burden was assessed by daily diary entries with information on AD and steroid days measuring 18 possible heritable, prenatal, and postnatal environmental exposures. RESULTS: The children with AD had a median (interquartile range) of 136 symptom days (61-294 days) and 72 steroid days (27-145 days) during the first 3 years of life, with the highest disease burden in the second year of life. The multivariable risk factor analysis showed that maternal AD and childhood allergic sensitization were associated with a higher number of AD days and maternal AD, filaggrin mutation, and allergic sensitization were associated with a higher number of steroid days. LIMITATIONS: Participants with a personal interest in atopic diseases could be more likely to participate. CONCLUSION: Children's burden of AD, assessed quantitatively as AD and steroid days, demonstrated positive associations with maternal AD, filaggrin mutation, and early-life allergic sensitization, with the highest disease burden in the second year of life.

Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis: protocol of a Danish intervention study.

INTRODUCTION: Lesional skin of atopic dermatitis (AD) is often colonised by Staphylococcus aureus and the bacterial abundance increases during a flare. However, the role of S. aureus and the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD. METHODS AND ANALYSIS: This clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologous S. aureus, staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression. ETHICS AND DISSEMINATION: The scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov: NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05578482, EudraCT 2021-006883-2.

Reduced Skin Microbiome Diversity in Infancy Is Associated with Increased Risk of Atopic Dermatitis in High-Risk Children.

It is currently unknown whether alterations in the skin microbiome exist before development of atopic dermatitis (AD). In this prospective Danish birth cohort of 300 children, we examined whether skin microbiome alterations during the first 2 months of life were associated with an increased risk of AD in the first 2 years and its severity after adjustment for environmental factors and selected skin chemokine and natural moisturizing factor levels. We found no overall association between the skin microbiome at birth and age 2 months and AD during the first 2 years of life. However, when restricting the analysis to children with at least one parent with atopy, a lower alpha diversity at age 2 months was associated with an increased risk of AD (adjusted hazard ratio = 1.7, 95% confidence interval = 1.1-2.6). We observed a stronger association in children where both parents had atopy (adjusted hazard ratio = 4.4, 95% confidence interval = 1.1-18.2). The putative pathogenic role of changes in the skin microbiome on AD risk remains uncertain but may play a role in those with an atopic predisposition.