Impact of systemic alitretinoin treatment on skin barrier gene and protein expression in patients with chronic hand eczema

Abstract

Background

Chronic hand eczema (CHE) is a common inflammatory skin disease that affects approximately 10% of the population. Systemic alitretinoin has been shown to be effective in CHE patients who are refractory to topical corticosteroids.

Objective

To analyse the impact of alitretinoin on the skin barrier genes and proteins expression in skin lesions of CHE patients.

Methods

Fifteen patients with CHE were treated with 30 mg/day of alitretinoin for up to 27 weeks. Disease severity was assessed using a clinical score. Skin biopsies from all the patients were evaluated before and after therapy for the expression of Ki-67, various skin barrier genes and TSLP by qPCR and immunohistochemistry.

Results

After alitretinoin application, an improvement in the clinical severity of CHE was observed in the majority of patients. Analysis of skin biopsies before treatment showed a significant increase in Ki-67 positive cells in the suprabasal layer and a dysregulated expression of various skin barrier genes like claudin 1, loricrin, filaggrin and cytokeratin 10, which were normalized after treatment. Thymic stromal lymphopoietin (TSLP) was significantly upregulated in CHE patient and also normalised after alitretinoin treatment and negatively correlated with filaggrin.

Conclusions

Our data indicate that the expression of barrier genes and proteins were normalised following treatment with alitretinoin in CHE. The change in expression levels of these genes correlated with the clinical efficacy, suggesting that alitretinoin exhibits a disease-modifying activity. TSLP is upregulated in CHE and seems to counteract filaggrin expression in the skin.

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