Atopic dermatitis epidemiology and unmet need in the United Kingdom

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

An investigation of the skin barrier restoring effects of a cream and lotion containing ceramides in a multi-vesicular emulsion in people with dry, eczema-prone, skin: The RESTORE study phase 1

Introduction The replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids. Methods A double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 μl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application). Results The test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h. Conclusion The sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3–4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis

The effect of an emollient containing urea, ceramide NP, and lactate on skin barrier structure and function in older people with dry skin

Xerosis affects up to 75% of older people and develops as a result of a skin barrier defect. Emollients are widely used to treat xerosis; however, there is limited understanding of the differences between them and their effects on the skin barrier in older people. This study aimed to compare the effect of a commercially available emollient containing 5% urea, ceramide NP and lactate (test emollient) to an alternative emollient without these additives (control emollient) on the properties of the skin barrier in older people. Two cohorts of 21 volunteers aged 60+ years with dry skin were recruited. The first applied the test emollient to one forearm and no treatment to the other for 28-days. The second compared the test emollient to the control emollient observing the same parameters. Effects on the skin barrier were determined by measuring skin barrier function, hydration, skin surface pH and by analyzing FTIR spectra before and after treatment. A third cohort of 6 young adults was recruited to investigate the effect of a single treatment with the test emollient on the molecular structure of the skin barrier at greater depths by employing the tape-stripping technique. The test emollient hydrated the skin to a significantly greater extent and for a longer period of time compared to the control emollient, an effect associated with a significant elevation of carboxylate groups (a marker of NMF content) within the stratum corneum. Furthermore, the test emollient imparted additional benefits to the structure and function of the skin barrier not exhibited by the control emollient. In conclusion the test emollient addressed the pathological features of xerotic aged skin, supporting its use as first-line therapy for xerotic skin conditions in this population

Quantification of natural moisturizing factors at the skin surface using a portable infrared spectrometer device: a pilot, calibration model

Attenuated total reflectance Fourier transform infrared spectroscopy (FTIR) is a useful technique for the molecular analysis of surfaces, including the skin, with promising translational clinical potential. Skin‐surface levels of natural moisturizing factor (NMF) are a biomarker of filaggrin (FLG) status (both inherited and acquired) and skin dryness. FLG‐related atopic dermatitis (AD) is associated with more severe and persistent disease. The objective of this study was to combine FTIR with chemometric analysis to generate a pilot calibration model for the in vivo quantification of NMF at the skin surface using a portable FTIR device. This study was performed in a climate‐controlled, skin barrier suite located at the University of Sheffield, U.K. patients with either healthy skin or AD were recruited from the local Sheffield community, and informed consent was obtained prior to enrolment in the study. A diagnosis of AD was made using the U.K. working party criteria, and disease severity was classified by the Eczema Area and Severity Index score. Genotyping for the five most common European loss‐of‐function FLG mutations was performed from buccal swabs. FTIR spectra of 4‐cm−1 resolution were collected from the volar forearm and antecubital fossa in conjunction with tape strips for the quantification of NMF components by high‐performance liquid chromatography (HPLC) and o‐phthaldialdehyde derivatization. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) measurements were collected as an assessment of barrier function. Ethical permission for this study was granted by the National Health Service Trent research ethics committee. Partial least‐squares regression modelling of absorbance in the mid infrared spectral region (1710–1185 cm−1) with skin‐surface NMF components determined by HPLC generated a predictive r2 value of 0.90. Modelling was superior on the antecubital fossa compared with the forearm, presumably due to the increased FTIR signal obtained from this site. Predicted NMF values correlated with FLG status, TEWL and SCH. FTIR combined with chemometric analysis is a suitable technique for the instantaneous in vivo quantification of NMF at the skin surface. The use of a portable FTIR device makes this methodology suitable for any clinical setting, with the potential to inform long‐term treatment strategies in AD

Infant Skin Barrier, Structure, and Enzymatic Activity Differ from Those of Adult in an East Asian Cohort

Skin physiology is dynamically changing over the frst years of postnatal life; however, ethnic variations are still unclear. Te aim of this study was to characterize infant skin barrier function, epidermal structure, and desquamation-related enzymatic activity as compared to that of adult skin in an East Asian population. Te skin properties of 52 infants (3-24 months) and 27 adults (20- 40 years) were assessed by noninvasive methods at the dorsal forearm and upper inner arm. Transepidermal water loss and skin surface conductance values were higher and more dispersed for infants compared to adults. Infant skin surface pH was slightly lower than adult on the dorsal forearm. Te infant SC and viable epidermis were thinner compared to adults with diferences that were site-specifc. Although the chymotrypsin-like activity for infant skin was comparable to adult level, the caseinolytic specifc activity was signifcantly higher for the infant cohort. Tese observations indicate a diferently controlled pattern of corneocyte desquamation in infants. In conclusion, structural and functional diferences exist between infant and adult skin in the East Asian population pointing to dynamic maturation of the epidermal barrier early in life

Sub-clinical assessment of atopic dermatitis severity using angiographic optical coherence tomography

Measurement of sub-clinical atopic dermatitis (AD) is important for determining how long therapies should be continued after clinical clearance of visible AD lesions. An important biomarker of sub-clinical AD is epidermal hypertrophy, the structural measures of which often make optical coherence tomography (OCT) challenging due to the lack of a clearly delineated dermal-epidermal junction in AD patients. Alternatively, angiographic OCT measurements of vascular depth and morphology may represent a robust biomarker for quantifying the severity of clinical and sub-clinical AD. To investigate this, angiographic data sets were acquired from 32 patients with a range of AD severities. Deeper vascular layers within skin were found to correlate with increasing clinical severity. Furthermore, for AD patients exhibiting no clinical symptoms, the superficial plexus depth was found to be significantly deeper than healthy patients at both the elbow (p = 0.04) and knee (p < 0.001), suggesting that sub-clinical changes in severity can be detected. Furthermore, the morphology of vessels appeared altered in patients with severe AD, with significantly different vessel diameter, length, density and fractal dimension. These metrics provide valuable insight into the sub-clinical severity of the condition, allowing the effects of treatments to be monitored past the point of clinical remission

Imaging striae distensae : a comparison between PS-OCT and digital dermoscopy

Stretch marks or striae distensae (SD) cause emotional distress and negatively affect the psychological well-being of patients. We investigate and compare two methods for quantifying the severity of SD: visual scoring of images captured using a clinical visible-light dermatological camera (C-Cube, Pixience Inc) and measuring the local birefringence of skin using polarization-sensitive optical coherence tomography (PS-OCT). Data on skin visually affected by SD and visually normal skin were collected from 19 human volunteers. Our results show a weak correlation between visual scores of the C-Cube images and the birefringence values obtained from the PS-OCT system. SD datasets have a significantly larger birefringence values compared to visually normal datasets

Characterization of skin barrier defects using infrared spectroscopy in patients with atopic dermatitis

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

Maintenance of an acidic skin surface with a novel zinc lactobionate emollient preparation improves skin barrier function in patients with atopic dermatitis

INTRODUCTION: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH. METHODS: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests. RESULTS: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m2/h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control. CONCLUSION: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens