Background The cytokine profile of atopic dermatitis (AD) depends on age, ethnicity, and disease severity. This study examined biomarkers in children with AD collected by tape strips and skin biopsies, and examined whether the levels differed with filaggrin genotype, disease severity, and food allergy. Methods Twenty‐five children aged 2–14 years with AD were clinically examined. Skin biopsies were collected from lesional skin and tape strips were collected from lesional and non‐lesional skin. We analyzed natural moisturizing factor (NMF) and 17 immune markers represented by mRNA levels in skin biopsies and protein levels in tape strips. Common filaggrin gene mutations were examined in all children. Results The cytokine profile in lesional skin was dominated by a T helper (Th) 2 response in skin biopsies, and by a general increase in innate inflammation markers (interleukin (IL)‐1α, IL‐1β, IL‐8, IL‐18) along with TARC and CTACK in tape strips. The levels of TARC, CTACK, IL‐8, IL‐18 showed significant correlation with AD severity in both lesional and non‐lesional tape stripped skin, while no significant correlations were observed in skin biopsy data. In tape strips from lesional and non‐lesional skin, the levels of NMF and selected cytokines differed significantly between children with and without FLG mutations and food allergy. Conclusion Sampling of the stratum corneum with non‐invasive tape strips can be used to identify biomarkers that are associated with disease severity, food allergy and FLG mutations. Skin biopsies showed robust Th2 signature but was inferior for association analysis regarding severity.

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Background Microbial dysbiosis with increased Staphylococcus aureus (S. aureus) colonization on the skin is a hallmark of atopic dermatitis (AD), however most microbiome studies focus on bacteria in the flexures and the microbial composition at other body sites have not been studied systematically. Objectives The aim of the study is to characterize the skin microbiome, including bacteria, fungi and virus, at different body sites in relation to AD, lesional state, and S. aureus colonization, and to test whether the nares could be a reservoir for S. aureus strain colonization. Methods Using shotgun metagenomics we characterized microbial compositions from 14 well defined skin sites from 10 patients with AD and 5 healthy controls. Results We found clear differences in microbial composition between AD and controls at multiple skin sites, most pronounced on the flexures and neck. The flexures exhibited lower alpha-diversity and were colonized by S. aureus, accompanied by S. epidermidis in lesions. Malassezia species were absent on the neck in AD. Virus mostly constituted Propionibacterium and Staphylococcusphages, with increased abundance of Propionibacterium phages PHL041 and PHL092 and Staphylococcus epidermidis phages CNPH82 and PH15 in AD. In lesional samples, both the genus Staphylococcus and Staphylococcus phages were more abundant. S. aureus abundance was higher across all skin sites except from the feet. In samples where S. aureus was highly abundant, lower abundances of S. hominis and Cutibacterium acnes were observed. M. osloensis and M. luteus were more abundant in AD. By single nucleotide variant analysis of S. aureus we found strains to be subject specific. On skin sites some S. aureus strains were similar and some dissimilar to the ones in the nares. Conclusions Our data indicate a global and site-specific dysbiosis in AD, involving both bacteria, fungus and virus. When defining targeted treatment clinicians should both consider the individual and skin site and future research into potential crosstalk between microbiota in AD yields high potential.

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Background: No biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the gold standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin-tape strips for molecular investigations enable noninvasive investigations of HE.Objective: By using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/ morphological subtypes was investigated.Methods: Thirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, nonlesional, and healthy skin. Total RNA was extracted and WTS was performed. Results:The largest molecular difference of HE patients with and without AD was found in nonlesional skin areas and included a downregulation of CXCL8 for HE patients without AD. Differences between allergic and irritant contact dermatitis included epidermal biomarkers such as EPHA1. Conclusion:Skin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes.atopic hand eczema, contact dermatitis, subtypes of hand eczema, tape stripping, transcriptomics | INTRODUCTIONHand eczema (HE) is a prevalent disease with a 1-year prevalence of 9% in the general population. 1 It may affect quality of life, impact work ability, 2,3 and require treatment periodically or continuously, depending on severity and chronicity. 4 HE may be a result of different etiologies, 5 which complicates both effective treatment and prevention. HE can be a part of atopic dermatitis (AD), and/or environmental factors such as exposure to allergens and/or irritants may result in allergic contact dermatitis (ACD) and/or irritant contact dermatitis (ICD) on the hands. The skin impairment of AD also makes the skin more vulnerable to irritants, sometimes leading to a mixed pattern of AD and ICD.Abbreviations: ACD, allergic contact dermatitis; AD, atopic dermatitis; DEG, differentially expressed gene; GO, gene ontology; HECSI, hand eczema severity index; HE +AD , hand eczema with atopic dermatitis; HE -AD , hand eczema without atopic dermatitis; HE, hand eczema; ICD, irritant contact dermatitis; WTS, whole transcriptome sequencing.

Background Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. Objective To characterize the plasma inflammatory signature of CHE. Methods Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, clinical- and self-reported variables were performed. Results Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper cell (Th)2, Th1, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe, but not mild AD, displayed systemic inflammation. Th2 markers chemokine (C-C motif) ligand (CCL)17 and CCL13 were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. Conclusion Systemic Th2-driven inflammation is shared between very severe, CHE without AD and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

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Background: Atopic dermatitis (AD) endotypes differ with ethnicity. We examined the skin microbiota, cytokine-, and lipid-profiles in Greenlandic Inuit and Danish children with AD. Methods: 25 Inuit children with AD and 25 Inuit control children were clinically examined and compared to previously collected data from 25 Danish children with AD. Skin tape strips and skin swabs were collected from lesional and non-lesional skin. Levels of cutaneous immune biomarkers, free sphingoid bases and their (glycosyl)ceramides were analyzed. Skin swabs were analyzed with 16S rRNA and tuf gene for characterization of bacterial species communities. Results: Bacterial β-diversity was significantly different between Inuit and Danish AD skin, in both lesional (p<0.001) and non-lesional (p<0.001) AD skin, and there was a higher relative abundance of Staphylococcus aureus in Danish compared to Inuit lesional (53% vs. 8%, p<0.01) and non-lesional skin (55% vs. 5%, p<0.001). Danish AD children had a higher α-diversity than Inuit children in non-lesional ( p<0.05) but not in lesional skin. Significantly higher levels of type 2 immunity cytokine interleukin (IL)-4 (p<0.05) and IL-5 (p<0.01) were identified in Inuit compared to Danish AD children. In contrast, IL-33 (p<0.01) was higher in Danish lesional and non-lesional AD skin. Higher levels of long-chain glucosylceramide (GlcCER)[S](d26:1) were found in lesional ( p<0.001) and non-lesional ( p<0.001) Inuit skin compared with Danish AD skin. NMF levels were similar in Inuit and Danish AD skin. Conclusion: Skin microbiota, cytokine and lipid composition differed significantly between Inuit and Danish children with AD and showed a stronger type 2 immune signature in Inuit children.