Road-traffic-related air pollution contributes to skin barrier alteration and growth defect of sensory neurons.

The effects of air pollution on health are gaining increasing research interest with limited data on skin alterations available. It was suggested that air pollution is a trigger factor for sensitive skin (SS). However, this data was based on surveys with a lack of experimental data. SS is related to altered skin nerve endings and cutaneous neurogenic inflammation. TTe present study was to assess the in vitro effect of particulate matter (PM) on epidermis and nerve ending homeostasis. PM samples were collected according to a validated protocol. Reconstructed human epidermis (RHE, Episkin®) was exposed to PM and subsequently the supernatants were transferred to a culture of PC12 cells differentiated into sensory neurons (SN). Cell viability, axonal growth and neuropeptide-release were measured. The modulation of the expression of different inflammatory, keratinocytes differentiation and neurites growth markers was assessed. PM samples contained a high proportion of particles with a size below 1 µm and a complex chemical composition. Transcriptomic and immunohistochemical analyses revealed that PM altered keratinocytes terminal differentiation and induced an inflammatory response. While viability and functionality of the SN were not modified, their outgrowth was significantly decreased after incubation with PM-exposed Episkin® supernatants. This was closely related to the modification of nerve growth factor/semaphorin 3A balance. This study showed that air pollutants have negative effects on keratinocytes and sensory nerve endings including inflammatory responses. These effects are probably involved in the SS pathophysiology and might be involved in inflammatory skin disorders.

Disease modification in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.

Short-term Heat Application Reduces Itch Intensity in Atopic Dermatitis: Insights from Mechanical Induction and Real-life Episodes.

Heat application is known to activate transient receptor potential (TRP) channels, which play a crucial role in sensory perception, including itch. In this study, the effect of a 5-s, 49°C heat application on itch intensity in atopic dermatitis (AD) patients was evaluated. The study comprised 2 parts: a controlled trial investigating the impact of brief heat treatment on mechanically induced itch, and a real-life study of AD patients experiencing itch attacks. A significant and immediate reduction in itch sensations following heat application was shown, with effects enduring over time. This response, however, showed notable individual variability, underscoring the potential of personalized approaches in AD treatment. Repeated applications of heat showed no habituation effect, suggesting its viability as a non-pharmacological, patient-tailored option for managing itch in AD. Further research in larger cohorts is warranted to refine treatment protocols and deepen understanding of the mechanisms involved.

Epidermal barrier function in dry, flaky and sensitive skin: A narrative review.

The stratum corneum (SC)-the outermost layer of the epidermis-is the principal permeability and protective barrier of the skin. Different components of the SC, including corneocytes, natural moisturizing factor, a variety of enzymes and their inhibitors, antimicrobial peptides and lipids, work interactively to maintain barrier function. The main barrier properties of the SC are the limitation of water loss and the prevention of infection and contact with potentially harmful exogenous factors. Although the SC functions consistently as a protective barrier throughout the body, variations in functions and morphology occur across body sites with age and skin type. Healthy SC function also depends on the interplay between the chemosensory barrier, the skin's microbiome and the innate immune system. Dysregulation of SC barrier function can lead to the development of skin disorders, such as dry, flaky or sensitive skin, but the complete underlying pathophysiology of these are not fully understood. This review provides insight into the current literature and emerging themes related to epidermal barrier changes that occur in the context of dry, flaky and sensitive skin. Additional studies are needed to further elucidate the underlying aetiology of dry, flaky and sensitive skin and to provide tailored treatment.

Stratum Corneum Hydration Measurements with a Bluetooth Wireless Probe: A Real-Life Study at Home Compared to Measurements under Laboratory Conditions.

INTRODUCTION: Non-invasive measurement of the stratum corneum hydration (SCH) with capacitance-based instrumentation is established in dermatological and cosmetic studies. We wanted to test the reliability of non-invasive self-measurements for SCH performed under real-life conditions by volunteers with a Bluetooth-based (wireless) probe Corneometer® (CM 825i) transmitting the data via a smartphone application to a central server. Probes and smartphones communicated using Bluetooth Low Energy. Data from the smartphone were securely transferred to a remote server in a different country with TLS encryption using HTTPS protocols. CM 825i values were correlated with the established CM 825 under laboratory conditions. The primary endpoint was the correlation of the two probes. Secondary endpoints were the coefficient of variation (CV) and delta values (before and after treatment). METHODS: Eighteen healthy volunteers (f: 8; m: 10) participated in the prospective observational study. The real-world home use of the wireless CM 825i was performed before and after treatments with base cream DAC for 7 days. RESULTS: Both instruments showed a significant and relevant correlation (p < 0.0001; Spearman coefficient of r = 0.8647). CM 825i and CM 825 differentiate significantly between normal and high SCH. Both devices showed comparable robustness in repeated measurements with a CV between 5.6% and 9.2%. CONCLUSION: We could show a significant correlation between both devices and a comparable differentiation between low and high SCH and comparable CVs. The real-life use demonstrated adequate acquiring and transmitting of in vivo data to a smartphone and subsequently transmitting to the secure server with low numbers of missed transmissions (<0.2%) and missed measurements (<5%).

Impact of multilamellar formulations on stratum corneum lipid organization and epidermal lipid barrier enhancement (Part II).

INTRODUCTION: The integrity of the stratum corneum (SC) is crucial for the skin's barrier function, protecting against environmental stressors and minimizing transepidermal water loss. Advances in skincare formulations have introduced multilamellar systems designed to emulate the SC's lipid composition and organization. This study hypothesizes that the application of a multilamellar cream will significantly impact the SC's lipid content and lamellar structure, thereby enhancing the epidermal barrier. METHODS: A saturated phosphatidylcholine-based multilamellar cream was applied to a cohort of adult subjects with very dry skin. Electron microscopy was utilized to analyse the micro-morphology of the cream and its integration into the lipid-depleted SC. Lipid analysis was conducted to quantify changes in the intercellular lipid matrix. RESULTS: Transmission-electron microscopy (TEM) imaging demonstrated that the multilamellar cream possesses a structured arrangement comparable to the natural SC architecture. Short-term application revealed a time-dependent restoration of lipid bilayers, while a 14-day regimen showed a marked increase in lipid lamellae density and length within the SC. Lipid analysis indicated a significant increase in total lipid content, with notable enhancements in ceramide and free fatty acid levels, without altering cholesterol levels. Lipid ratio analysis further confirmed the rebalancing of the SC's lipid composition. DISCUSSION: The multilamellar cream selectively increased specific lipids critical for barrier function, suggesting an action mechanism that aligns with the skin's natural regulatory processes. This selective augmentation indicates the potential of the formulation to not only restore but also enhance the epidermal barrier, with the maintenance of physiological lipid ratios suggesting compatibility with intrinsic repair mechanisms. CONCLUSION: The study confirms that a multilamellar cream can significantly improve the SC's lipid composition and structural integrity, indicating enhanced barrier function. They are pivotal for skincare professionals, dermatologists, and product developers, enriching the understanding of multilamellar creams' benefits and applications in improving epidermal barrier function.

INTRODUCTION: l'intégrité de la couche cornée (SC, stratum corneum) est essentielle pour la fonction de barrière cutanée, protégeant contre les facteurs de stress environnementaux et réduisant au minimum la perte d'eau transépidermique. Les progrès en matière de formulations pour soins de la peau ont introduit des systèmes multilamellaires conçus pour simuler la composition et l'organisation lipidique du SC. Cette étude émet l'hypothèse que l'application d'une crème multilamellaire aura un impact significatif sur la teneur en lipides et la structure lamellaire du SC, améliorant ainsi la barrière épidermique. MÉTHODES: Une crème multilamellaire à base de phosphatidylcholine saturée a été appliquée à une cohorte de sujets adultes présentant une peau très sèche. La microscopie électronique a été utilisée pour analyser la micromorphologie de la crème et son intégration dans le SC délipidé. Une analyse lipidique a été réalisée pour quantifier les changements dans la matrice lipidique intercellulaire. RÉSULTATS: l'imagerie par TEM a démontré que la crème multilamellaire possède un agencement structuré comparable à l'architecture naturelle du SC. L'application à court terme a révélé une restauration dépendante du temps des bicouches lipidiques, tandis qu'un schéma posologique de 14 jours a montré une augmentation marquée de la densité et de la longueur des lamelles lipidiques au sein du SC. L'analyse lipidique a indiqué une augmentation significative de la teneur lipidique totale, avec des améliorations notables des taux de céramide et d'acides gras libres, sans altérer les taux de cholestérol. L'analyse du rapport lipidique a confirmé le rééquilibrage de la composition lipidique du SC. DISCUSSION: la crème multilamellaire a augmenté de manière sélective les lipides spécifiques essentiels à la fonction de barrière, suggérant un mécanisme d'action qui s'aligne sur les processus de régulation naturels de la peau. Cette augmentation sélective indique le potentiel de la formulation non seulement à restaurer, mais également à améliorer la barrière épidermique, avec le maintien des rapports lipidiques physiologiques suggérant une compatibilité avec les mécanismes de réparation intrinsèques. CONCLUSION: l'étude confirme qu'une crème multilamellaire peut améliorer de manière significative la composition lipidique et l'intégrité structurelle du SC, ce qui indique une meilleure fonction de barrière. Ils sont essentiels pour les professionnels de la peau, les dermatologues et les développeurs de produits, et enrichissent la compréhension des bénéfices et des applications des crèmes multilamellaires dans l'amélioration de la fonction de la barrière épidermique.

Clinical efficacy of a multilamellar cream on skin physiology and microbiome in an epidermal stress model: A controlled double-blinded study.

INTRODUCTION: Stratum corneum (SC) is essential for skin barrier function, mitigating water loss and shielding against potentially harmful substances and allergens. The SC's lipid matrix, arranged in a lamellar structure, is integral to its protective role. Our study explores the restoration effects of a multilamellar cream with an acidic pH compared to a basic placebo cream on skin physiology and its interaction with the skin microbiome after stress induction via tape stripping (TS). MATERIALS AND METHODS: In this double-blind study, 14 healthy participants aged 21-58 years were assessed pre- and post-tape stripping, followed by a 14 days application of a multilamellar test cream and a placebo cream with evaluations on days 7, 14 and 17 for sustained effects. Skin physiology was analysed in terms of epidermal barrier function, SC hydration and surface pH. The microbiome was analysed by 16S rRNA amplicon sequencing the 16S rRNA gene using Illumina MiSeq, with subsequent species identification. RESULTS: Our study showed significant improvements in skin barrier repair and SC hydration with verum, particularly after 14 days of application, while both creams initially enhanced stratum corneum hydration. No significant changes in surface-pH were detected. The skin microbiome analysis revealed that TS slightly decreased alpha diversity, a trend that verum significantly reversed, enhancing diversity beyond baseline levels after 14 days. Overall, while both creams contributed to a broader microbial phyla diversity over time, no significant changes in the abundance of specific genera or species were noted between treatments. DISCUSSION AND CONCLUSION: Our study delineates the efficacy of a pH-optimized multilamellar cream in enhancing epidermal barrier recovery and SC hydration post-sequential TS, in contrast to an unstructured basic placebo. Verum cream significantly improved skin barrier function and SC hydration at day 14, with sustained effects evident beyond the treatment period. Furthermore, the multilamellar formulation facilitated the restitution of cutaneous microbiome diversity, a key indicator of healthy skin ecology, underscoring the symbiotic relationship between barrier integrity and microbial composition. These findings underscore the importance of multilamellar emollient structures in dermatological therapeutics, with potential implications for the design of advanced skincare interventions that holistically support cutaneous resilience and homeostasis.

INTRODUCTION: La couche cornée (stratum corneum, SC) est essentielle pour la fonction de barrière cutanée, atténuant la perte d'eau et protégeant contre les substances et allergènes potentiellement nocifs. Disposée selon une structure lamellaire, la matrice lipidique de la SC est constitutive de son rôle protecteur. Notre étude explore les effets de restauration d'une crème multilamellaire à pH acide par rapport à une crème placebo de base sur la physiologie de la peau et son interaction avec le microbiome de la peau après induction de stress via un test tape stripping (TS). MATÉRIELS ET MÉTHODES: Dans cette étude en double aveugle, 14 participants en bonne santé âgés de 21 à 58 ans ont été évalués avant et après tape stipping, puis ont procédé à l'application pendant 14 jours d'une crème test multilamellaire et d'une crème placebo avec des évaluations aux jours 7, 14 et 17 pour les effets durables. La physiologie de la peau a été analysée en termes de fonction de la barrière épidermique, d'hydratation SC et de pH de surface. Le microbiome a été analysé par séquençage de l'amplicon de l'ARNr 16S sur le gène de l'ARNr 16S à l'aide d'Illumina MiSeq, avec identification ultérieure des espèces. RÉSULTATS: Notre étude a montré des améliorations significatives de la réparation de la barrière cutanée et de l'hydratation SC avec le traitement actif, en particulier après 14 jours d'application, tandis que les deux crèmes avaient initialement amélioré l'hydratation de la couche cornée. Aucun changement significatif du pH de surface n'a été détecté. L'analyse du microbiome cutané a révélé que le TS diminuait légèrement la diversité alpha, une tendance qui s'est significativement inversée avec le traitement actif : une amélioration de la diversité au­delà des taux initiaux était observée après 14 jours. Dans l'ensemble, bien que les deux crèmes aient contribué à une plus grande diversité des phyla microbiennes au fil du temps, aucune variation significative dans l'abondance de genres ou d'espèces spécifiques n'a été observée entre les traitements. DISCUSSION ET CONCLUSION: Notre étude délimite l'efficacité d'une crème multilamellaire à pH optimisé pour améliorer la réparation de la barrière épidermique et l'hydratation SC après un TS séquentiel, contrairement à un placebo basique non structuré. La crème contenant le traitement actif a significativement amélioré la fonction de barrière cutanée et l'hydratation SC au jour 14, avec des effets durables évidents au­delà de la période de traitement. En outre, la formulation multilamellaire a facilité la restitution de la diversité du microbiome cutané, un indicateur clé d'une écologie de peau en bonne santé, soulignant la relation symbiotique entre l'intégrité de la barrière et la composition microbienne. Ces résultats soulignent l'importance des structures émollientes multilamellaires dans les traitements dermatologiques, avec des implications potentielles pour la conception d'interventions cutanées avancées qui soutiennent de manière holistique la résilience cutanée et l'homéostasie.

In vivo transepidermal water loss: Validation of a new multi-sensor open chamber water evaporation system Tewameter TM Hex.

BACKGROUND: Instrumentation technology for transepidermal water loss measurements has not been substantially modified since its introduction by Nilsson in 1977. Recent progress in sensor development allowed a new sensor arrangement using a matrix of 30 sensors. Raw measurement values are processed with spatial statistical analysis. We aimed to compare the new, multi-sensor probe (Tewameter TM Hex) with the established Tewameter TM 300 probe and to gain reference data for the new parameters of transepidermal energy loss and water vapor concentration on skin. MATERIAL AND METHODS: Baseline measurements and repeated measurements on the volar forearm and assessment on eight different anatomical locations were performed on 24 healthy volunteers (both gender) with the TM Hex and the TM 300. RESULTS: A significant correlation (p < 0.001; R-coefficient = 0.9) between TM Hex and the TM 300 with a low coefficient of variance (CV) 11% for TM Hex and 19% for TM 300, could be assessed. The CV ranged between 7% (right inner upper arm) and 14% (palms). Average transepidermal heat loss ranged from 12 W/m2 on the lower leg to 38.8 W/m2 on the palm. CONCLUSION: The correlation between TM Hex and TM 300 along with the robustness of the measurements with the TM Hex shows that the new probe for assessment of epidermal barrier function is comparable to the TM 300. In most conditions, TM Hex provides more accurate measurements than TM 300. New parameters open the field to studying skin's water and energy balance.

Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients.

INTRODUCTION: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. METHODS: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. RESULTS: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. CONCLUSION: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Les multiples fonctions protectrices de la peau découlent des interactions entre les cellules épithéliales de la peau et les cellules immunitaires, ainsi que le microbiote commensal. Développée au cours du dernier trimestre de la vie intra-utérine, la barrière cutanée s'adapte de manière dynamique après la naissance. Des différences spécifiques dans la structure et la physiologie ont été mises en évidence entre la peau des nourrissons et celle des adultes. La couche cornée des nourrissons est plus fine et structurée par des cornéocytes plus épais avec une surface plus anisotrope par rapport à la peau adulte. Des niveaux plus faibles des NMF et de ses constituants, ainsi qu'une activité protéasique accrue dans l'épiderme entraînent une sécheresse de la peau du bébé et une adaptation continue de la desquamation à l'environnement extra-utérin. L'épiderme du nourrisson est caractérisé par un taux de prolifération accéléré et une barrière de perméabilité cliniquement compétente chez les nouveau-nés nés à terme, malgré les valeurs de base plus élevées de la perte insensible d'eau transépidermique chez les nourrissons. La surface de la peau des nouveau-nés est moins acide, ce qui pourrait augmenter la susceptibilité aux dermatites fessières et atopiques. Immédiatement après la naissance, la peau est colonisée par des bactéries commensales-un processus dépendant du mode d'accouchement et d'une importance majeure pour la maturation du système immunitaire. La diversité et la dysbiose bactériennes de la peau ont été associées à différentes pathologies telles que la dermatite atopique et séborrhéique. Cet article se concentre sur l'adaptation structurelle, fonctionnelle et biochimique de la barrière cutanée humaine après la naissance. Nous discutons des interactions sur l'axe "barrière cutanée/microbiote/système immunitaire" et de leur rôle dans le développement d'une intégrité fonctionnelle compétente de la barrière épidermique.

Acidic Skin Care Promotes Cutaneous Microbiome Recovery and Skin Physiology in an Acute Stratum Corneum Stress Model.

INTRODUCTION: Skin microbiome and skin physiology are important indicators of the epidermal homeostasis status. Stress models can reveal pathological conditions and modulating effects. Here we investigated the cutaneous microbiome in relation to skin physiology after mild tape stripping (TS) without treatment compared to two cosmetic leave-on lotions (pH 5.5 vs. pH 9.3) in 25 healthy volunteers. METHODS: The microbiome was analyzed by 16S-rRNA-gene amplicon sequencing and put in relation to the following skin physiology parameter: epidermal barrier function (TEWA-Meter TM300), stratum corneum hydration (Corneometer CM 825), surface pH (pH-Meter), and skin erythema (Mexameter). RESULTS: TS reduced the alpha diversity with a recovery over 7 days without treatment. Both lotions significantly accelerated the recovery of the alpha diversity already after 2 days with a slightly higher rate for the acidic lotion. After TS, the relative abundance of Proteobacteria was increased, whereas Actinobacteria were reduced. The relative abundances of typical skin-associated genera were reduced after TS. Taxa compositions returned to normal levels after 7 days in all treatment groups. An accelerated normalization could be observed with both lotions already after 2 days. A significant difference in skin pH was observed on day 2 and day 7 with an increased pH for the alkaline lotion. Both lotions induced an increase in stratum corneum hydration. CONCLUSION: The study proved the suitability of an experimental stress model in the assessment of skin surface microbiome in relation to skin physiology. Stratum corneum hydration increased significantly with both lotions already at day 2. Microbiome parameters (alpha diversity, mean relative taxa, abundance of selected genera) normalized over 2-7 days. The following mechanisms could be responsible for the accelerated normalization of the microbiome: (a) optimized hydration during the recovery phase, (b) the composition of the lotion, (c) the induced repair mechanism. Thus, the formulation has a positive effect on the stratum corneum hydration and subsequently on cutaneous microbiome and skin physiology. Furthermore, this eventually has implications on the modulation of exogenous stress-induced epidermal alterations.

Association between barrier impairment and skin microbiota in atopic dermatitis from a global perspective: Unmet needs and open questions.

Atopic diathesis encompassing atopic dermatitis (AD), allergic rhinoconjunctivitis, food allergy, eosinophilic esophagitis, and asthma is a widely prevalent condition with a broad heterogeneity in clinical course, age of onset, and lifespan persistence. A primary event in AD is the commonly inherited epidermal barrier dysfunction. Together with the host-microbiome interactions, barrier defect and allergen exposure modulate both innate and adaptive immunity, thus triggering and maintaining the inflammatory response. Microbiome diversity, together with the host's contact with nonpathogenic microbes in childhood, is a prerequisite for functional maturation of the immune system, which is in part mediated by microbiome-induced epigenetic changes. Yet, whether microbiome alterations are the result or the reason for barrier impairment and inflammatory response of the host is unclear. Exposure to locally prevalent microbial species could contribute to further modification of the disease course. The objective of this review is to reveal the link between changes in the skin microbiota, barrier dysfunction, and inflammation in AD. Addressing unmet needs includes determining the genetic background of AD susceptibility; the epigenetic modifications induced by the microbiota and other environmental factors; the role of globally diverse provoking factors; and the implementation of personalized, phenotype-specific therapies such as a epidermal barrier restoration in infancy and microbiota modulation via systemic or topical interventions, all of which open gaps for future research.

Teledermatology in Times of COVID-19 Confinement: Comparing Patients' and Physicians' Satisfaction by the Standardized Brest Teledermatology Questionnaire.

The French government imposed the first COVID-19 pandemic lockdown from March 17 until May 11, 2020. Only emergency cases and teledermatology (TD) were allowed in outpatient settings. A standardized questionnaire was developed to compare the satisfaction level of patients and their treating physicians. Our main question was whether the patients would perceive TD as a valid alternative for direct physical face-to-face consultation. Eighty-two patients and their 4 treating dermatologists from one dermatology department participated in the study (43 females, 39 males) with a mean age of 46.6 years (SD ±23.9). The reason for TD was a chronic disease in the majority (87.8%), and mainly as a follow-up (96.3%). Regarding satisfaction, almost all categories rated around 9 on a 0-10 verbal analogue scale. The same level of global satisfaction could be seen between the patients and the physicians as well as for the quality of the patient-physician relation and whether all questions could be addressed during the TC. Physicians showed significantly higher scores than patients only for the category of "length" of the consultation. Gender, age, as well as distance between the clinic and home of the patient were not influencing factors for satisfaction. Regarding the technical parameters, the evaluation was mostly comparable for patients and physicians, but overall lower than the relational satisfaction parameters, especially for image quality. Patients were significantly more motivated to continue the TD after the lockdown than their treating dermatologists. We see an interest for implementing TD in specialized centers with chronic patients coming from remote places for regular follow-ups. TD cannot replace in-person patient-physician interaction, but was helpful during the lockdown. As a result, TD might become part of dermatology training to prepare for future lockdown situations.

Proposal for Cut-off Scores for Sensitive Skin on Sensitive Scale-10 in a Group of Adult Women.

Sensitive skin is commonly assessed on the basis of self-reports from patients, and sometimes questionnaires, such as the Sensitive Scale-10, are used. The severity of sensitive skin follows a continuum, from the absence of sensitive skin to very sensitive skin. The aims of this cross-sectional study were to compare subjects with and without symptomatic sensitive skin and to propose diagnostic criteria for sensitive skin. A total of 160 women, between 18 and 65 years of age, with and without sensitive skin, and without any associated skin diseases, were recruited. Mean age was 41 years old. Fifty-five percent of participants reported having "very sensitive" or "sensitive" skin. In the sensitive skin group, the participants mainly experienced skin irritability (100%), tautness (97.5%), discomfort (90%) and redness (90%). According to the receiver operating characteristic curve, a Sensitive Scale-10 (SS-10) cut-off value of 12.7 can be used to detect sensitive skin (with a sensitivity of 72.4% and specificity of 90.3%).

Epidermal carotenoid levels in vivo of patients with plaque psoriasis: Effects of narrow-band UVB phototherapy.

BACKGROUND: Psoriasis is a systemic inflammatory disease characterized by hindered antioxidant defense and increased formation of free radicals. There are limited data on the skin carotenoids in psoriatic skin as well as their modulation during narrow-band UVB (NB-UVB) phototherapy of the disease. AIM: The aim of this prospective study is to reveal the skin carotenoids levels during NB-UVB phototherapy of psoriasis in humans. MATERIAL AND METHODS: Twenty Caucasian subjects with mild-to-moderate plaque psoriasis (15m; 5f) were enrolled in the study, and nine gender- and age-matched healthy volunteers were recruited for controls of oxidative stress measurements. All psoriasis patients underwent 10 sessions of NB-UVB phototherapy. Measurements were taken at baseline and after 10 sessions of NB-UVB phototherapy. The assessment of carotenoid levels in the skin in vivo was performed by a non-invasive, reflectance spectroscopy-based device. Psoriasis severity was assessed by psoriasis area and severity index (PASI). The dermatology life quality index (DLQI) was evaluated in psoriatic patients. RESULTS: Baseline carotenoid levels were significantly lower in psoriasis patients in comparison to healthy controls. NB-UVB phototherapy insignificantly diminished carotenoid levels in the skin of psoriasis patients, while clinical improvement both in PASI score and DLQI was observed. CONCLUSION: We showed the levels of skin carotenoids in psoriatic patients are lower than in healthy subjects. NB-UVB did not change significantly skin carotenoid levels. Further studies should elucidate the potential effect of antioxidants supplementation during NB-UVB of psoriasis.

Pacific-Ciguatoxin-2 and Brevetoxin-1 Induce the Sensitization of Sensory Receptors Mediating Pain and Pruritus in Sensory Neurons.

Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome.

Application of parelectric spectroscopy to detect skin cancer-A pilot study.

BACKGROUND: The early detection of skin cancer is still challenging and calls for objective, fast diagnostic, and ideally non-invasive methods in order to leave the potentially malignant tumor cells unaltered. In this paper, the parelectric spectroscopy was applied to evaluate the potential of a non-invasive detection of basal cell carcinoma (BCC) and malignant melanoma. MATERIALS AND METHODS: A prototype of parelectric spectroscopy was used to investigate non-invasively dipole density and mobility of suspicious skin lesions. The differences in investigated tissue were analyzed compared to pathohistological findings in a clinical study on 51 patients with suspected BCC and malignant melanoma. RESULTS: The non-invasive parelectric spectroscopy could differentiate between normal skin, BCC, and melanoma but failed to distinguish between different types of skin cancer. The data were normalized to unsuspected nearby skin because the different skin locations influence dipole density and mobility. CONCLUSION: The results of the pilot study indicate that the parelectric spectroscopy might be an additional, useful non-invasive diagnostic procedure to distinguish between normal skin and skin cancer.

EEMCO Guidance for the in vivo Assessment of Biomechanical Properties of the Human Skin and Its Annexes: Revisiting Instrumentation and Test Modes.

Biomechanics of the skin is an important subject in skin research. It has been studied for many decades involving various technologies and methods to characterize and quantify mechanical properties of the skin under different in vivo conditions. The present EEMCO paper reviews the current rel-evant information, providing practical orientation to researchers dedicated to in vivo assessment of biomechanics of skin and its annexes. We discuss the available non-invasive instruments, including their principles and variables. A correspondence between the descriptors nomenclature proposed by Agache and the designation for the suction-based standard instruments is proposed. The addressed properties include skin softness/stiffness, firmness, elasticity, elastic and viscoelastic properties, extensibility, resilience, anisotropy, acoustical shock wave hardness, friction (in relation to topographic properties), thickness, fiber/stress mechanics (bending, cyclic, tensile, fatigue, or torsion), and hardness. We provide the relation of these properties to biomechanical descriptors and in some cases to SI units. Practical guidance for the proper use of these instruments, limitations, and possible interpretations are provided, while discussing the meaning of descriptive or "phenomenological" variables. For studies intended to quantify the effect of an intervention with regard to mechanical properties, we recommend a minimum of 30-40 participants, based on normal distribution of the data sets. Some important limitations are recognized, including the lack of standardization of procedures and calibration of instruments, which compromises the relevance and real nature of the descriptors/parameters obtained with these devices. The present work highlights an approach to a better practice and a science-supported biomechanical assessment of human skin, hair, and nails.

Atopic Patients Show Increased Interleukin 4 Plasma Levels but the Degree of Elevation Is Not Sufficient to Upregulate Interleukin-4-Sensitive Genes.

BACKGROUND: Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitroanalyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes. OBJECTIVE: To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (n = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes. METHODS: 34 allergic patients suffering from allergic rhinitis (n = 11), atopic eczema (n = 11) and allergic asthma (n = 12) as well as 9 healthy control individuals were recruited. IgE and IL-4 plasma levels were determined by ELISA, and the expression of selected IL-4-sensitive gene products in blood leukocytes was quantified by qRT-PCR. In addition, the fatty acid oxygenase activity of isolated monocytes was measured by RP-HPLC analysis of the arachidonic acid oxygenation products (ex vivo activity assays). RESULTS: We found that plasma levels of IgE and IL-4 were significantly elevated in atopic patients but the degree of elevation was not sufficient to upregulate the expression of the selected IL-4-sensitive genes in circulating leukocytes. Moreover, the arachidonic acid oxygenase activity of blood monocytes was not significantly altered in atopic patients. CONCLUSION: Our data suggest that the IL-4 plasma levels of atopic patients are not high enough to impact the expression of IL-4-sensitive genes.

Stratum corneum targeting by dendritic core-multishell-nanocarriers in a mouse model of psoriasis.

Inflammatory disorders of the skin pose particular therapeutic challenges due to complex structural and functional alterations of the skin barrier. Penetration of several anti-inflammatory drugs is particularly problematic in psoriasis, a common dermatitis condition with epidermal hyperplasia and hyperkeratosis. Here, we tested in vivo dermal penetration and biological effects of dendritic core-multishell-nanocarriers (CMS) in a murine skin model of psoriasis and compared it to healthy skin. In both groups, CMS exclusively localized to the stratum corneum of the epidermis with only very sporadic uptake by Langerhans cells. Furthermore, penetration into the viable epidermis of nile red as a model for lipophilic compounds was enhanced by CMS. CMS proved fully biocompatible in several in vitro assays and on normal and psoriatic mouse skin. The observations support the concept of CMS as promising candidates for drug delivery in inflammatory hyperkeratotic skin disorders in vivo.