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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. Objectives 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, and 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 (Th)2- and 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. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) 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. Conclusions Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

Background Epidermal deficiency of filaggrin, and the derived natural moisturizing factors (NMFs), is associated with increased risk of atopic dermatitis (AD). While filaggrin gene mutations cause filaggrin deficiency, there is limited insight into the causative environmental factors. Objectives To explore the effect of selected exogenous skin stressors on NMF and skin cytokine levels in healthy adult epidermis. Methods Forty healthy volunteers (aged 18-49 years) were exposed to hard, soft and chlorinated water, 0·5% sodium lauryl sulfate, house dust mite, cat allergen, staphylococcal enterotoxin B (SEB), cooling and histamine. Participants were tape-stripped and biophysiological measurements performed. NMF was determined after 24 and 48 h, whereas skin cytokines were measured after 24 h for selected exposures. Results At 24 h, a significant decrease in NMFs was observed for soft (0·51 ± 0·19 g m-2 h-1 ) and hard water (0·61 ± 0·32 g m-2 h-1 ) compared with occlusion alone (0·71 ± 0·18 g m-2 h-1 ). Hard water led to increased levels of interleukin (IL)-4, interferon (IFN)-γ and IL-10. Exposure to house dust mite and SEB led to a significant decrease in NMFs after 24 h (0·77 ± 0·28 and 0·80 ± 0·28 g m-2 h-1 , respectively) compared with occlusion alone (1·00 ± 0·42 g m-2 h-1 ). House dust mite led to an increase in IFN-γ, IL-2 and IL-4 vs. the nonoccluded control site. Conclusions Based on experimental exposure to selected atopic skin stressors, we conclude that NMFs levels are decreased along with increased secretion of various skin cytokines in healthy individuals. Our data highlight environmental factors that might play a role in AD pathophysiology.

SummaryBackground During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather-exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF). Objectives To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults. Methods Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18–40 years and 40 aged ≥ 70 years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface texture was done (Dermal Texture Index, DTI). Potential confounders were registered and adjusted for. Results In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self-reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the summer, and female participants had higher NMF levels than male participants. Conclusions Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis.