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Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis
Anna S Quaade1, Xing Wang2, Julie B K Sølberg1
1The National Allergy Research Centre, Department of Dermatology and Allergy, Copenhagen University Hospital Herlev-Gentofte, Hellerup, Denmark.
Insights
Chronic hand eczema (CHE) and atopic dermatitis (AD) share systemic inflammation, particularly T helper 2 (Th2) driven pathways. This suggests Th2-targeting therapies may benefit severe CHE patients.
Area of Science:
- Immunology
- Dermatology
- Proteomics
Background:
- Chronic hand eczema (CHE) is a common and debilitating skin condition.
- The association between CHE and systemic inflammation remains largely unexplored.
- Understanding the inflammatory profile of CHE is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the plasma inflammatory signature in patients with chronic hand eczema (CHE).
- To compare the inflammatory profiles of CHE patients with and without a history of atopic dermatitis (AD).
- To explore correlations between inflammatory markers and disease severity.
Main Methods:
- Utilized Proximity Extension Assay technology to analyze 266 inflammatory and cardiovascular risk proteins in plasma.
- Included 40 healthy controls, 57 patients with active AD, 11 with CHE and prior AD, and 40 with CHE and no prior AD.
- Assessed filaggrin gene mutation status and performed correlation analyses between biomarkers and clinical variables.
Main Results:
- Very severe CHE without prior AD showed significant systemic inflammation compared to controls.
- Increased levels of T helper (Th)2, Th1, general inflammation, and eosinophil markers correlated with CHE severity.
- Th2 markers, CCL17 and CCL13, were significantly elevated in severe CHE and moderate-to-severe AD, indicating shared inflammatory pathways.
Conclusions:
- Systemic T helper 2 (Th2)-driven inflammation is a common feature in very severe CHE (no prior AD history) and moderate-to-severe AD.
- These findings suggest that targeting Th2 pathways could be a potential therapeutic strategy for specific subtypes of CHE.
- The study highlights the importance of considering systemic inflammation in the management of severe chronic hand eczema.
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.
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