Atopic dermatitis displays stable and dynamic skin transcriptome signatures.

BACKGROUND: Skin transcriptome studies in atopic dermatitis (AD) showed broad dysregulation as well as "improvement" under therapy. These observations were mainly made in trials and based on microarray data. OBJECTIVES: Our aim was to explore the skin transcriptome and the impact of systemic treatment in patients of the TREATgermany registry. METHODS: Biopsy specimens from 59 patients with moderate-to-severe AD before and 30 patients 12 weeks after start of systemic treatment (dupilumab [n = 22] or cyclosporine [n = 8]) and from 31 healthy controls were subjected to mRNA sequencing. Differential expression, pathway enrichment, correlation, and coexpression network analysis were conducted. RESULTS: Both lesional and nonlesional skin showed a stable "core" signature characterized by disturbed epidermal differentiation and activation of IL-31/IL-1 signaling. A second dynamic signature showed progressive enrichment for type 2 inflammation, TH17 signaling, and natural killer cell function. Markers correlated with disease activity have functions in epidermal barrier properties and immune modulation. IL4RA was among the top 3 central dysregulated genes. Cyclosporine led to a more pronounced global transcriptome reversion and normalized TH17 cell/IL23 signaling, whereas dupilumab led to a stronger increase in level of epidermal differentiation markers. Both treatments strongly decreased levels of type 2 markers, but overall the residual profile was still profoundly different from that of healthy skin. Lower levels of IL4RA and IL13 and high IL36A expression were related to a stronger clinical response to dupilumab. CONCLUSION: The AD core signature is characterized by dysregulation of genes related to keratinocyte differentiation and itch signaling. A dynamic signature reflects progressive immune responses dominated by type 2 cytokines with an additional role of TH17 and natural killer cell signaling.

Effectiveness of secondary prevention in metalworkers with work-related skin diseases and comparison with participants of a tertiary prevention program: A prospective cohort study.

BACKGROUND: In Germany, a multistep approach has been established to prevent work-related skin diseases (WRSDs). OBJECTIVES: To evaluate the effect of a secondary individual prevention program (SIP) in metalworkers with WRSD and to compare their characteristics with those of participants of a tertiary individual prevention program (TIP). PATIENTS AND METHODS: In a prospective cohort study, metalworkers with WRSD of the hands participating either in the SIP (n = 114) or in the TIP (n = 83) were recruited. At baseline and at the respective follow-up 8-12 weeks after the SIP or at dismissal from the TIP (3-4 weeks later), questionnaires were completed and the severity of WRSD was assessed. Saliva samples were collected for assessment of filaggrin (FLG) mutations and an explorative genome-wide association study (GWAS). RESULTS: Ninety-three SIP patients (81.6%) attended the follow-up. Disease severity was significantly reduced, and knowledge and protective behavior were significantly improved compared to baseline. Significant differences between SIP and TIP patients were found regarding duration and severity of symptoms, work absenteeism, tobacco smoking, and presence of atopic dermatitis, but not regarding FLG mutations and by GWAS. CONCLUSIONS: The SIP was effective in metalworkers with WRSDs. Individual factors may influence the course of the disease and the need for the TIP.