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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.

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.

INTRODUCTION: Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption.OBJECTIVES: We examined whether intensive daily whole-body TCS treatment over two weeks followed by twice weekly application for four weeks could elicit insulin resistance and increase bone resorption in adults with AD.METHODS: A randomized parallel-group double-blind double-dummy non-corticosteroid-based active-comparator study design was completed in Copenhagen, Denmark. Thirty-six non-obese, non-diabetic adults with moderate-to-severe AD were randomized to whole-body treatment with betamethasone 17-valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after two weeks of daily treatment and after further four weeks of twice-weekly maintenance treatment.RESULTS: AD severity improved with both treatments and systemic inflammation was reduced. After two weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone (n=18) and tacrolimus (n=18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both two and six weeks but remained unchanged in the tacrolimus arm.CONCLUSIONS: Whole-body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short-term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS.

Background There is currently no insight into biomarkers that can predict the onset of pediatric atopic dermatitis (AD). Methods Nested in a prospective birth cohort study that examined the occurrence of physician-diagnosed AD in 300 children, 44 random children with onset of AD in the first year of life were matched on sex and season of birth with 44 children who did not develop AD. Natural moisturizing factor (NMF), corneocyte surface protrusions, cytokines, free sphingoid bases (SBs) of different chain lengths and their ceramides were analyzed from tape strips collected at 2 months of age before onset of AD using liquid chromatography, atomic force microscopy, multiplex immunoassay, and liquid chromatography mass spectrometry, respectively. Results Significant alterations were observed for four lipid markers, with phytosphingosine ([P]) levels being significantly lower in children who developed AD compared with children who did not (median 240 pmol/mg vs. 540 pmol/mg, p < 0.001). The two groups of children differed in the relative amounts of SB of different chain lengths (C17, C18 and C20). Thymus- and activation-regulated chemokine (TARC/CCL17) was slightly higher in children who developed AD, whereas NMF and corneocyte surface texture were similar. AD severity assessed by the eczema area and severity index (EASI) at disease onset was 4.2 (2.0;7.2). [P] had the highest prediction accuracy among the biomarkers (75.6%), whereas the combination of 5 lipid ratios gave an accuracy of 89.4%. Conclusion This study showed that levels and SB chain length were altered in infants who later developed AD, and that TARC/CCL17 levels were higher.

Background Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. Objectives To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. Methods In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. Results At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21–3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. Conclusions It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD., Background Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear. Objectives To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not. Methods In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses. Results At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset. Conclusions It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.

This prospective birth cohort followed 150 preterm and 300 term newborns during the first year of life to assess possible differences in risk factors, age at onset, anatomical location, and severity of atopic der-matitis. Atopic dermatitis was diagnosed clinically, and severity was assessed using Eczema Area Severity Index (EASI). DNA was analysed for filaggrin gene mutations. Parents were asked about environmental exposures and emollient use. Atopic dermatitis during the first year of life was observed in 21.2% of children and was more common in term children compared with preterm children (26.7% vs 11.7%, p < 0.001), with lower age of onset (4 vs 6 months, p < 0.05) and more severe disease at onset (EASI: 4.8 vs 0.4, p < 0.0005). Environmental risk factors for atopic dermatitis were essentially similar for preterm and term born children, apart from winter and autumn births. Filaggrin gene mutations were less common in preterm than term children (4.1% vs 9.2%, p = 0.06).

We explored differences between lesional and non-lesional skin and anatomical variation in epidermal biomarker levels using stratum corneum (SC) tape strips in adult patients with atopic dermatitis (AD). SC tape strips from three distinct anatomical locations (upper extremity, trunk and lower extremity) and serum samples were collected from 25 adult patients with AD (mean age 34.8 years). Inflammatory cytokines in tape strips and serum, natural moisturizing factor (NMF), skin pH, and trans-epidermal water loss (TEWL) were measured. Disease severity was assessed using SCORing of Atopic Dermatitis (SCORAD) scores, respectively, global (overall) and local (lesion specific based on objective signs) SCORAD(1).

[Introduction]: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. [Areas covered]: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. [Expert commentary]: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine.

Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. Areas covered: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. Expert commentary: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine.

Skin diseases represent one of the most common work-related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis (CD), which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier are different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without the involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signalling pathways during the sensitization phase required for the activation of T-cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens but also by the generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to the development of ICD and ACD.