Role of Keratinocytes in Sensitive Skin

Sensitive skin is a clinical syndrome defined by the occurrence of unpleasant sensations such as burning, stinging, tingling, pricking, or itching in response to various normally innocuous physical, chemical, and thermal stimuli. These particular symptoms have led the consideration of a potential dysfunction of the intra-epidermal nerve fibers (IENF) that are responsible for pain, temperature, and itch perception. This neuronal hypothesis has just been reinforced by recent studies suggesting that sensitive skin could become assimilated to small fiber neuropathy. Meanwhile, the involvement of keratinocytes, the pre-dominant epidermal cell type, has so far mainly been considered because of their role in the epidermal barrier. However, keratinocytes also express diverse sensory receptors present on sensory neurons, such as receptors of the transient receptor potential (TRP) family, including Transient Receptor Potential Vallinoid 1 (TRPV1), one of the main transducers of painful heat which is also involved in itch transduction, and Transient Receptor Potential Vallinoid 4 (TRPV4) which is depicted as a heat sensor. While TRPV1 and TRPV4 are expressed both by sensory neurons and keratinocytes, it has recently been demonstrated that the specific and selective activation of TRPV1 on keratinocytes is sufficient to induce pain. Similarly, the targeted activation of keratinocyte-expressed TRPV4 elicits itch and the resulting scratching behavior. So, contrary to classical conception, the IENF are not the exclusive transducers of pain and itch. In light of these recent advances, this review proposes to consider the putative role of epidermal keratinocytes in the generation of the unpleasant sensations characteristic of sensitive skin syndrome

Tattooing : A national survey in the general population of France

Non peer reviewe

Sensitive Skin in the Indian Population: An Epidemiological Approach

Sensitive skin is a very frequent condition, the prevalence of this syndrome has been studied in different countries in Europe, in United States and in Japan. The aim of the study was to evaluate the epidemiology of sensitive skin in the Indian population, like this has never been studied in this country. A representative nationwide sample of the Indian population aged 15 and over was selected. Individuals were selected as per the quota method (based on sex, age, householder profession, rural/urban location, and region). In total, 27.9% of men and 36.7% of women declared having “sensitive” or “very sensitive” skin. The difference between the 2 sexes was very significant. Of these, 5.1% of men and 7.2% of women reported having “very sensitive” skin. The subjects complaining about “sensitive” or “very sensitive” skin were 2–4 times more likely to declare suffering from atopic dermatitis, acne, psoriasis, or vitiligo. They were 2 to 3 times more reactive to climatic factors, environmental factors, cosmetics and food intake. In conclusion, although less frequently reported than in other countries, sensitive skin is a frequent condition in India, affecting about one third of the population

Itch characteristics in five dermatoses: non-atopic eczema, atopic dermatitis, urticaria, psoriasis and scabies.

International audienceItch is a frequent symptom in many diseases. Some studies have used questionnaires to evaluate pruritus by targeting a single type of dermatitis, for example, studying atopic dermatitis (AD) with the "Eppendorf Itch Questionnaire"(1, 2), and uraemic pruritus (3). Questionnaires have also been used to study psoriasis (4) and urticaria (5). The pathophysiological mechanisms of itch, especially with regard to the mediators and transmitters involved, can vary according to the itch-inducing disease. It is possible that itching sensations may be experienced differently by each patient and depending on the underlying disease. O'Neill et al. (6) and Reich et al. (7) have shown that itching sensations can vary between various skin diseases. The present study used an exploratory approach to highlight the qualitative (symptomatological) features of pruritus in different dermatoses, using a non-validated questionnaire in French, adapted from previous questionnaires (1, 2)

Sensitive Skin: Lessons From Transcriptomic Studies

In 2016, a special interest group from the International Forum for the Study of Itch defined sensitive skin (SS) as a syndrome that manifests with the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) after stimuli that should not cause a reaction, such as water, cold, heat, or other physical and/or chemical factors. The pathophysiology of sensitive skin is still poorly understood, but the symptoms described suggest inflammation and peripheral innervation. Only two publications have focused on sensitive skin transcriptomics. In the first study, the authors performed a microarray comparison of SS and non-sensitive skin (NSS) samples and showed differences in the expression of numerous genes in SS and NSS samples. Moreover, in the SS samples, two clusters of genes were identified, including upregulated and downregulated genes, compared to NSS samples. These results provide some interesting clues for the understanding of the pathophysiology of SS. The second study compared SS and NSS samples using RNA-seq assays. This method allowed the identification of long non-coding RNAs (lncRNAs) and differentially expressed mRNAs and provided a comprehensive profile in subjects with SS. The results showed that a wide range of genes may be involved in the pathogenesis of SS and suggested pathways that could be associated with them. In this paper, we discuss these two studies in detail and show how transcriptomic studies can help understand the pathophysiology of sensitive skin. We call for new transcriptomic studies on larger populations to be conducted before putative pathogenic mechanisms can be detected and analyzed to achieve a better understanding of this complex condition

The Virtual Reality applied to the biology understanding: the in virtuo experimentation

International audienceThe advent of the computer and computer science, and in particular virtual reality, offers new experiment possibilities with numerical simulations and introduces a new type of investigation for the complex systems study: the in virtuo experiment. This work lies on the framework of multi-agent systems. We propose a generic model for systems biology based on reification of the interactions, on a concept of organization and on a multi-model approach. By 'reification' we understand that interactions are considered as autonomous agents. The aim has been to combine the systemic paradigm and the virtual reality to provide an application able to collect, simulate, experiment and understand the knowledge owned by different biologists working around an interdisciplinary subject. Here, we have been focused on the urticaria disease understanding. Autonomy is taken as a principle. The method permits to integrate different natures of model in the same application using chaotic asynchronous iterations and C++ library: AReVi. We have modeled biochemical reactions, molecular 3D diffusion, cell organizations and mechanical 3D interactions. It also permits to embed different expert system modeling methods like fuzzy cognitive maps. This work provides a toolbox easily adaptable to new biological studies

Perceived stress in patients with inflammatory and non-inflammatory skin conditions. An observational controlled study among 255 Norwegian dermatological outpatients

Background Inflammation may increase stress, while stress may promote inflammation. Most dermatological conditions are chronic and inflammatory, while some, such as cancer, naevi and tumours are non-inflammatory, but may cause stress because of the fear of malignancy and the necessity for surgical and other invasive treatments. Stress among patients with skin diseases is little explored. Objectives To assess perceived stress in patients with inflammatory and non-inflammatory skin conditions compared to healthy controls. Methods Observational cross-sectional study. Consecutive outpatients (N = 255) visiting the Department of Dermatology, Stavanger University Hospital, Norway and 148 skin-healthy controls contributed by answering questionnaires on sociodemographics, stressful life events, economic difficulties, self-rated health and perceived stress. The validated Perceived Stress Scale10 was used to evaluate stress. A dermatologist examined patients and registered their diagnoses and comorbidities. Controls included in this study were not examined by a dermatologist and self-reported their comorbidities. Results Patients with an inflammatory skin disease or psoriasis have a tripled risk of reporting moderate to high stress compared with controls when adjusted for relevant confounders, including having experienced a stressful life event recently or having a comorbidity. Patients with a purely non-inflammatory skin disease perceived stress no differently than controls. Conclusion Patients with inflammatory skin disease perceived higher stress than controls and patients with non-inflammatory skin conditions. Dermatologists may play a role in awareness of the importance of stress in skin disease.publishedVersio

Merkel Cell Polyomavirus Small T Antigen mRNA Level Is Increased following In Vivo UV-Radiation

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer involving Merkel cells. Recently, a new human polyomavirus was implicated in MCC, being present in 80% of the samples analyzed. In virus-positive MCC, the Merkel cell polyomavirus (MCPyV) is clonally integrated into the patients DNA, and carries mutations in its large T antigen, leading to a truncated protein. In non-symptomatic tissue MCPyV can reside at very low levels. MCC is also associated with older age, immunosuppression and sun exposure. However, the link with solar exposure remains unknown, as the precise mechanism and steps involved between time of infection by MCPyV and the development of MCC. We thus investigated the potential impact of solar simulated radiation (SSR) on MCPyV transcriptional activity. We screened skin samples of 20 healthy patients enrolled in a photodermatological protocol based on in vivo-administered 2 and 4 J/cm2 SSR. Two patients were infected with two new variants of MCPyV, present in their episomal form and RT-QPCR analyses on SSR-irradiated skin samples showed a specific and unique dose-dependent increase of MCPyV small t antigen transcript. A luciferase based in vitro assay confirmed that small t promoter is indeed UV-inducible. These findings demonstrate that solar radiation has an impact on MCPyV mRNA levels that may explain the association between MCC and solar exposure