Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis.

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.

The Proteome of Hand Eczema Assessed by Tape Stripping.

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.

The transcriptome of hand eczema assessed by tape stripping.

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.

Prevalence, incidence, and severity of hand eczema in the general population - A systematic review and meta-analysis.

Accurate assessments of the burden of hand eczema (HE) in the general population are important for public awareness and intervention. The aim of this systematic review and meta-analysis was to provide updated estimates of prevalence and incidence, alongside additional epidemiological endpoints on HE in the general population. PubMed, Embase and Web of Science were searched for studies reporting the prevalence and/or incidence of HE in the general population. Proportion meta-analyses were performed to calculate pooled estimates of prevalence, incidence, severity, and the proportion of individuals with HE and a history of atopic dermatitis. Sixty-six studies were included in the quantitative analysis encompassing 568 100 individuals. The pooled estimates for lifetime, 1-year, and point prevalence were 14.5% (95% confidence interval [CI]: 12.6-16.5), 9.1% (95% CI: 8.4-9.8) and 4.0% (95% CI: 2.6-5.7), respectively. The pooled incidence rate of HE was 7.3 cases/1000 person-years (95% CI: 5.4-9.5). The occurrence of HE was 1.5-2 times higher in females than males. More than one third suffered from moderate/severe disease and around one third had a history of atopic dermatitis. HE was a recurrent, long-lasting disease with an average age at onset of the early- to mid-twenties. In conclusion; HE is a highly prevalent disease in the general population and carries a significant risk of long-term or chronic disease.

Increased occurrence of hand eczema in young children following the Danish hand hygiene recommendations during the COVID-19 pandemic.

BACKGROUND: During the first wave of the COVID-19 pandemic of Spring 2020, Denmark was one of the first countries to introduce lockdown measures, including closing of all daycare centers. Following the reopening of daycare centers, Danish Health Authorities implemented a mandatory intensive hand hygiene regimen. OBJECTIVES: To examine the occurrence and point prevalence of hand eczema as a consequence of more intensive hand hygiene among Danish children attending daycare. METHODS: The heads of 1667 daycare centers in Denmark were contacted and asked to forward a link to a questionnaire to parents of the children attending the daycare center. RESULTS: Among 6858 children, 12.1% had hand eczema before reopening of daycare centers, whereas 38.3% reported hand eczema after the children returned to daycare. Of the children who never had hand eczema, 28.6% developed hand eczema after returning to daycare. The risk of hand eczema was significantly associated with atopic dermatitis, female gender, higher age, and frequency of handwashing. CONCLUSION: Following the implemented hygiene regimen, a high proportion of young children rapidly developed hand eczema. Well-established prophylactic skin care might have spared a proportion of the children from developing hand eczema.