Epidermal Barrier in Atopic Dermatitis

Atopic dermatitis (AD) is a complex disease that affects up to 20% of children and impacts the quality of patients and families in a significant manner. New insights into the pathophysiology of AD point to an important role of structural abnormalities in the epidermis combined with immune dysregulation. Filaggrin (FLG) is synthesized as a large precursor, profilaggrin, and is expressed in the upper layers of the epidermis. FLG plays a critical role in the epidermal barrier, and FLG mutations cause abnormal epidermal function. FLG mutations are strongly associated with early-onset, and persistent severe AD. In addition, FLG deficiency in the epidermis is related to allergic sensitization and asthma. The basic skin care including repair and protection of the skin barrier with proper hydration and topical anti-inflammatory therapy is important to control the severity of skin disease in patients with AD

A phase i study of daily treatment with a ceramide-dominant triple lipid mixture commencing in neonates

<p>Abstract</p> <p>Background</p> <p>Defects in skin barrier function are associated with an increase risk of eczema and atopic sensitisation. Ceramide-dominant triple lipid mixture may improve and maintain the infant skin barrier function, and if shown to be safe and feasible, may therefore offer an effective approach to reduce the incidence of eczema and subsequent atopic sensitisation. We sort to assess the safety and compliance with daily application of a ceramide-dominant triple lipid formula (EpiCeram™) commencing in the neonatal period for the prevention of eczema.</p> <p>Methods</p> <p>Ten infants (0-4 weeks of age) with a family history of allergic disease were recruited into an open-label, phase one trial of daily application of EpiCeram™ for six weeks. The primary outcomes were rate of compliance and adverse events. Data on development of eczema, and physiological properties of the skin (transepidermal water loss, hydration, and surface pH) were also measured.</p> <p>Results</p> <p>Eighty percent (8/10) of mothers applied the study cream on 80% or more of days during the six week intervention period. Though a number of adverse events unrelated to study product were reported, there were no adverse skin reactions to the study cream.</p> <p>Conclusions</p> <p>These preliminary results support the safety and parental compliance with daily applications of a ceramide-dominant formula for the prevention of eczema, providing the necessary ground work for a randomised clinical trial to evaluate EpiCeram™ for the prevention of eczema.</p> <p>Trial registration</p> <p>The study was listed at the Australian/New Zealand Clinical Trial Registry (ANZCTR): reg. no. <a href="http://www.anzctr.org.au/ACTRN12609000727246.aspx">ACTRN12609000727246</a>.</p

Filaggrin Genotype Determines Functional and Molecular Alterations in Skin of Patients with Atopic Dermatitis and Ichthyosis Vulgaris

BACKGROUND: Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD). Filaggrin (FLG) loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV), which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes. OBJECTIVE: The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected. METHODS AND FINDINGS: Patients with AD/IV (n = 43) and controls (n = 15) were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL) and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI). Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression. CONCLUSIONS: We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction

The Effect of Water Hardness on Surfactant Deposition after Washing and Subsequent Skin Irritation in Atopic Dermatitis Patients and Healthy Control Subjects

Living in a hard water area is associated with an increased risk of atopic dermatitis (AD). Greater skin barrier impairment after exposure to surfactants in wash products, combined with the high calcium levels of hard water and/or high chlorine levels, is a compelling mechanism for this increase. The purpose of this study was to investigate this mechanism in individuals with and without a predisposition to skin barrier impairment. We recruited 80 participants: healthy control subjects and AD patients with and without FLG mutations. The skin of each participant was washed with sodium lauryl sulfate in water of varying hardness levels and chlorine concentrations, rinsed, and covered with chambers to determine the effects of surfactant residues. Sites washed with hard water had significantly increased sodium lauryl sulfate deposits. These deposits increased transepidermal water loss and caused irritation, particularly in AD patients carrying FLG mutations. A clear effect of chlorine was not observed. Water softening by ion-exchange mitigated the negative effects of hard water. Barrier impairment resulting from the interaction between hard water and surfactants is a contributory factor to the development of AD. Installation of a water softener in early life may be able to prevent AD development. An intervention study is required to test this hypothesis

Developments in silicone technology for use in stoma care

YesSoft silicone's flexibility, adhesive capacity and non-toxic, non-odourous and hypoallergenic nature have made it an established material for adhesive and protective therapeutic devices. In wound care, silicone is a component of contact layer dressings for superficial wounds and silicone gel sheeting for reducing the risk of scarring, as well as of barriers for incontinence-associated dermatitis. Regarding stoma accessories, silicone is established in barrier films to prevent contact dermatitis, adhesive removers to prevent skin stripping and filler gels to prevent appliance leaks. Until recently, silicone has not been used in stoma appliances flanges, as its hydrophobic nature has not allowed for moisture management to permit trans-epidermal water loss and prevent maceration. Traditional hydrocolloid appliances manage moisture by absorbing water, but this can lead to saturation and moisture-associated skin damage (MASD), as well as increased adhesion and resultant skin tears on removal, known as medical adhesive-related skin injury (MARSI). However, novel silicone compounds have been developed with a distinct evaporation-based mechanism of moisture management. This uses colloidal separation to allow the passage of water vapour at a rate equivalent to normal trans-epidermal water loss. It has been shown to minimise MASD, increase wear time and permit atraumatic removal without the use of adhesive solvents. Trio Healthcare has introduced this technology with a range of silicone-based flange extenders and is working with the University of Bradford Centre for Skin Sciences on prototype silicone-based stoma appliance flanges designed to significantly reduce the incidence of peristomal skin complications, such as MARSI and MASD. It is hoped that this will also increase appliance wear time, reduce costs and improve patient quality of life