Impaired Skin Barrier Function and Downregulated Expression of Caspase-14 in Moderate to Severe Chronic Hand Eczema

Abstract

Aim: To investigate whether the skin barrier function is impaired with regard to the pH value, water content, transepidermal water loss (TEWL), and the integrity of the stratum corneum, and whether the expression of caspase-14 is altered in moderate to severe chronic hand eczema (CHE). Methods: Thirty patients with moderate to severe CHE treated at our institute and 30 healthy volunteers were included in this study. The pH value, water content, TEWL, and the integrity of the stratum corneum were measured in all subjects. Results: Significantly increased pH value, decreased water content, elevated TEWL, and impaired integrity of the stratum corneum were observed in the lesional skin of CHE patients compared with the nonlesional skin of CHE patients and the normal skin of healthy volunteers. The expression of caspase-14 decreased in the lesional and nonlesional skin of CHE patients compared with the normal skin of healthy volunteers, especially prominent in the nonlesional skin. The mean optical density (OD) value of immunohistochemical staining for caspase-14 was significantly lower in the nonlesional skin than in the lesional skin and normal skin (p < 0.01 for both). Although the mean OD value was lower in the lesional skin than in the normal skin, the difference was not statistically significant (p > 0.05). Conclusion: Skin barrier dysfunction indeed occurs in CHE patients, which may be related to mechanisms associated with a downregulated expression of caspase-14.

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges

“…Tape strips are becoming more frequently used to study biomarker expression in skin diseases allowing for a more comprehensive understanding of its pathogenesis and paving the way for future treatment development. [152][153][154][155][156][157] Increasing the understanding of underlying immune profiles of the different CHE phenotypes will allow for the development of valuable therapeutics and continued investigation of immune-based therapeutics such as delgocitinib, gusacitinib, and dupilumab.…”

Altered Epidermal Permeability Barrier Function in the Uninvolved Skin Supports a Role of Epidermal Dysfunction in the Pathogenesis of Occupational Hand Eczema

“…Moreover, reductions in filaggrin content were found in lesional skin of hand eczema, supporting a possible role for the epidermal permeability barrier function in the pathogenesis of hand eczema [9]. Second, while deficiency in caspase 14 impairs the epidermal permeability barrier [10], the uninvolved skin of hand eczema subjects displays a lower expression of caspase 14 [11]. Third, deficiencies in late cornified envelope proteins, LCE3B and LCE3C, other structural proteins of the barrier, are associated with allergic contact dermatitis [12].…”

“…Whether such genes were altered in these subjects is unknown. A pathogenic role for a defective epidermal permeability barrier in hand eczema has long been proposed, because (1) expression levels of barrier-related proteins, including filaggrin and caspase 14, decline in the lesional skin of hand eczema [9,11], (2) TEWL rates increase in lesional skin and adjacent nonlesional skin [11], (3) topical barrier repair strategies delay the relapses of and/or improve hand eczema [24,25] and (4) skin disorders, such as atopic dermatitis, with a defective permeability barrier are risk factors of hand eczema [26]. However, direct evidence to support the role of epidermal permeability dysfunction in hand eczema is far less sufficient.…”

Caspase-14—From Biomolecular Basics to Clinical Approach. A Review of Available Data

“…The expression of caspase-14 is decreased in the lesional and non-lesional skin of patients with chronic hand eczema. It was found to be correlated with increased pH value, decreased water content, increased TEWL (transepidermal water loss), and the impaired integrity of the cornified layer of the epidermis [ 60 ].…”