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Background Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC). Objectives To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity. Methods We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped. Results Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm–1 (full width half maximum) and 1340 cm–1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = –0.59, carboxylate peak area r = –0.50). Conclusions ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies. [ABSTRACT FROM AUTHOR]

Skin irritancy to topically applied chemicals is a significant problem that affects millions of people worldwide. New or modified chemical entities must be tested for potential skin irritancy by industry as part of the safety and toxicity profiling process. Many of these tests have now moved to a non‐animal‐based format to reduce experiments on animals. However, these tests for irritancy potential often rely on monolayer cultures of keratinocytes that are not representative of the skin architecture or tissue‐engineered human skin equivalents (HSE) using complex multi‐gene expression panels that are often cumbersome and not amenable for high throughput. Here, we show that human skin equivalents increase abundance of several phosphorylated kinases (c‐Src, c‐Jun, p53, GSK3α/β) in response to irritant chemical stimulation by phosphokinase array analysis. Specific phosphorylation of c‐SrcY419 was confirmed by immunoblotting and was plasma membrane‐associated in basal/spinous cells by phospho‐specific immunohistochemistry. Moreover, c‐SrcY419 phosphorylation in response to the irritants lactic acid and capsaicin was inhibited by the c‐Src inhibitors KB‐SRC and betaine trimethylglycine. These data provide the first evidence for c‐Src specific activation in response to chemical irritants and point to the development of new modes of rapid testing by immunodetection for first‐pass screening of potential irritants. This study demonstrates that specific kinases, in particular c‐Src, are activated in HSE in response to chemical irritants. The rapid increase in specific phosphorylated signal transduction molecules upon exposure to irritants may prove ideal targets to rapidly identify and differentiate potential chemical irritants from non‐irritants. [ABSTRACT FROM AUTHOR]

The article discusses the role of emollients in preventing atopic dermatitis (AD) and the mixed results from studies on this topic. The article highlights a recent study by Rehbinder et al. that examined the effects of emollient intervention on the skin barrier in babies. The study found that the intervention had a disruptive effect on the condition of the skin barrier, which was unexpected. The article also mentions that some emollients can harm the skin and discusses their different effects on corticosteroid uptake and cutaneous sensitivity to irritants. Despite the mixed results, the article suggests that there is still potential for exploring the use of barrier-enhancing emollients in preventing AD. [Extracted from the article]

A topical vehicle is a 'carrier system' for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition. [ABSTRACT FROM AUTHOR]

Background: Hard domestic water has been reported to worsen atopic eczema (AE) and may contribute to its development in early life. Objective: To review the literature on the relationship between the effect of water hardness (high calcium carbonate; CaCO3) on (a) the risk of developing AE, (b) the treatment of existing AE and (c) skin barrier function in human and animal studies. Design , data sources and eligibility criteria: We systematically searched databases (MEDLINE, Embase, Cochrane CENTRAL, GREAT and Web of Science) from inception until 30/6/2020. Human and animal observational and experimental studies were included. The primary outcomes were risk of AE and skin barrier function. Studies were meta‐analysed using a random effects model. Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: Sixteen studies were included. Pooled observational data from seven studies on 385,901 participants identified increased odds of AE in children exposed to harder versus softer water (odds ratio 1.28, 95% CI 1.09, 1.50; GRADE certainty: very low). Two mechanistic studies in humans reported higher deposition of the detergent sodium lauryl sulphate in those exposed to harder versus softer water. Two randomized controlled trials comparing water softeners with standard care did not show a significant difference in objective AE severity with softened water (standardized mean difference 0.06 standard deviations higher, 95% CI 0.16 lower to 0.27 higher; GRADE certainty: moderate). Conclusions & Clinical Relevance: There was a positive association between living in a hard water (range: 76 to > 350 mg/L CaCO3) area and AE in children. There is no evidence that domestic water softeners improve objective disease severity in established AE. There may be a role of water hardness in the initiation of skin inflammation in early life, but there is a need for further longitudinal and interventional studies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin condition associated with a significant health-related and socioeconomic burden, and is characterized by intense itch, disruption of the skin barrier, and upregulation of type 2-mediated immune responses. The United Kingdom (UK) has a high prevalence of AD, affecting 11–20% of children and 5–10% of adults. Approximately 2% of all cases of childhood AD in the UK are severe. Despite this, most AD treatments are performed at home, with little contact with healthcare providers or services. Here, we discuss the course of AD, treatment practices, and unmet need in the UK. Although the underlying etiology of the disease is still emerging, AD is currently attributed to skin barrier dysfunction and altered inflammatory responses. Management of AD focuses on avoiding triggers, improving skin hydration, managing exacerbating factors, and reducing inflammation through topical and systemic immunosuppressants. However, there is a significant unmet need to improve the overall management of AD and help patients gain control of their disease through safe and effective treatments. Approaches that target individual inflammatory pathways (e.g. dupilumab, anti-interleukin (IL)-4 receptor α) are emerging and likely to provide further therapeutic opportunities for patient benefit. [ABSTRACT FROM AUTHOR]