Hand eczema (HE) is a prevalent skin disease. However, the classification of HE into different subtypes remains challenging. A limited number of previous studies have employed invasive biopsy-based strategies; yet, studies of the HE proteome using noninvasive tape-stripping methodology have not been reported. In this study, we wanted to assess whether global proteomic analysis of skin tape strip samples can be used for subclassification of patients with HE. Tape strips were collected from patients with HE and healthy skin. Liquid chromatography-mass spectrometry proteomics was performed, and the global protein expression was analyzed. We identified 2,919 proteins in stratum corneum-derived skin cells from tape strip samples. Compared with healthy skin, the lesional samples from patients with HE exhibited increased expression of immune-related markers and a decreased expression of structural barrier proteins. The difference between HE subtypes was restricted to the lesional skin areas and included an increased expression of skin barrier-related proteins independently of the concurrent AD. In conclusion, we found that the noninvasive tape strip method used in combination with liquid chromatography-mass spectrometry proteomics can be used for analysis of skin protein expression in patients with HE. Thus, the method shows potential for assessing the proteomic differences between subtypes of HE and biomarker discovery.

Background: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures.Objectives: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes.Methods: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well‐characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self‐reported variables were performed.Results: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non‐atopic dermatitis‐like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes.Conclusion: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema.

Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. To characterize the plasma inflammatory signature of CHE. 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 (CHE^PREVIOUS_AD), and 40 with CHE and no history of AD (CHE^NO_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. Very severe CHE^NO_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 CHE^NO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHE^NO_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 CHE^NO_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 CHE^NO_AD and AD. 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.