D. Falcone

What Is Sensitive Skin? A Systematic Literature Review of Objective Measurements

Despite sensitive skin being highly prevalent, no consensus on the definition and pathomechanism of sensitive skin exists. Here we report the results of a systematic literature review of diagnostic methods for sensitive skin at clinical, histological and biophysical levels. A systematic search revealed 27 out of 1,701 articles which we appraised in detail. Impaired skin barrier function and increased vascular reactivity are most often associated with sensitive skin. We identified key reasons causing an ambiguity around the sensitive skin phenomenon. We propose using standardized selection methods of subjects by a multifactorial questionnaire spanning a range of provocations, including those of chemical, mechanical and environmental origin, followed by clinical, histological and top-notch biophysical measurements. This could lead to a breakthrough in the understanding of the sensitive skin phenomenon, fueling advances of biomedical and dermatological science.

Gram-positive anaerobe cocci are underrepresented in the microbiome of filaggrin-deficient human skin

Mutations in the filaggrin gene, which cause the skin disease ichthyosis vulgaris and are a genetic risk factor for atopic dermatitis, alter the cutaneous microbiome thereby affecting keratinocyte host defense responses following skin barrier disruption

Clinical, biophysical and immunohistochemical analysis of skin reactions to acute skin barrier disruption - a comparative trial between participants with sensitive skin and those with nonsensitive skin

DEAR EDITOR, One out of two women and one out of three men in the Western world reports having sensitive skin (SS). Individuals classifying themselves as having SS frequently describe stinging, burning or itching sensations of the skin, and erythema and dryness may accompany these sensations. As a response to this, unravelling the pathophysiology of this condition and developing solutions for individuals with SS has become an important topic in biomedical and cosmetic research fields. Although many clinical evaluations and biophysical techniques have been applied in order to shape understanding of and create consensus on the causal pathways of SS, no diagnostic test has been found to be sufficiently sensitive and reproducible. The prevalence of SS and burden on dermatologists stress the urgent need for recognition of SS, and the necessity of gaining more knowledge to reach a consensus on its pathomechanism. Previous studies proposed potential pathways that may lead to a condition commonly designated as SS: impaired barrier function, sensory hyper-reactivity, inflammatory or vascular responsiveness and atopic predisposition. Unfortunately, studies show inconsistent outcomes, impeding identification of key pathways in the mechanism of SS. In explorative studies, many provocations used as a diagnostic method for SS have resulted in sensory skin reactions; however, susceptibility to one provocative agent does not predict susceptibility to another. In this study, we aimed to identify key features in the morphology and physiology of skin reactions and skin recovery in participants with SS. We evaluated skin reactions to standardized provocation using an in vivo model for barrier disruption in selected participants. Evaluation was performed dynamically, that is at baseline and at several time points after acute barrier disruption. As tape stripping is widely used as a reproducible in vivo human model of cutaneous injury and regeneration, this allows the study of SS in a dynamic fashion. In order to reduce confounding by concomitant skin conditions, we propose an experimental design with exclusion of skin diseases. We are of the opinion that a multifactorial questionnaire encompassing a range of provocations, including chemical, mechanical and thermal origins, and multiple signs and symptoms could be a more adequate selection tool than topical agents only. These methods, combining self-reported skin sensitivity with biophysical and detailed histological evaluation of skin responses, could enable the exploration of a range of processes and delivery of decisive answers to questions on causal pathways of SS, and explain previously described inconsistencies. Participants were recruited via student websites. Volunteers filled out a questionnaire (Appendix S1; see supporting information) on self-assessed skin sensitivity and skin perceptions (i.e. discomfort, stinging, redness or dryness) following potential endogenous and exogenous triggers (i.e. toiletries, shaving, emotions, heat, cold and clothes). The severity of reactions was scored on a visual analogue scale (VAS), and duration of reactions on an ordinal scale [i.e. no experience, seconds, minutes, < 1 h, hour(s), day(s)]. The investigator scored the 24 VAS scores and 24 durations (recoded to scores of 0, 1, 2, 4, 7 and 10, respectively) of the questionnaire. The upper and lower quartiles of the sumscore of these 48 items (range 0–480) was determined in a large cohort study (n = 238, manuscript in preparation). A participant in the present study was defined as having SS if the sumscore was above the upper quartile value and the patient reported SS. A participant was defined as having nonsensitive skin (NSS) if the sumscore was below the lower quartile value and the patient reported NSS. Participants were included if the following criteria were met: had SS or NSS according to the procedure described above; had Fitzpatrick skin type II or III; did not have or have had an atopic condition [asthma, allergic rhinoconjunctivitis or atopic dermatitis (AD)]; was able to give written informed consent; had no skin disease, including contact dermatitis. Participants were advised not to apply cosmetics for 24 h before the first visit. Groups with SS and NSS skin were sex matched. The experiments were approved by the local ethics committee (METC, region Arnhem-Nijmegen) and were conducted to conform with the principles of the Declaration of Helsinki. Sequential tape stripping of four skin sites parallel to the upper side of the intergluteal cleft was performed using a metal oblong plate with an oval aperture (13 9 22 mm, 2 9 cm) covered by 6890 polyvinylchloride tape (Scotch Tape; 3M, St Paul, MN, U.S.A.) to standardize extension of the skin and velocity and angle of removal. Stripping was stopped when the skin became homogeneously refulgent. Macroscopic images were taken as a reference and tapes were counted.

Microspectroscopic Confocal Raman and Macroscopic Biophysical Measurements in the in vivo Assessment of the Skin Barrier: Perspective for Dermatology and Cosmetic Sciences

Skin barrier function, confined to the stratum corneum, is traditionally evaluated using established, noninvasive biophysical methods like transepidermal water loss, capacitance and conductance. However, these methods neither measure skin molecular composition nor its structure, hindering the actual causes of skin barrier change or impairment. At the same time, confocal Raman microspectroscopy (CRS) can directly measure skin molecular composition and structure and has proven itself to be a powerful technique for biomolecular analysis. The aims of this literature review were to evaluate noninvasive biophysical methods in view of CRS and to outline a direction towards more specific and informative skin measurement methods. We address this by investigating, for the first time, the relation between in vivo assessment of the skin barrier using indirect biophysical methods and the actual skin composition and structure as given by CRS, and emphasize the high potential of CRS for dermatology and cosmetic sciences. CRS acceptance in these fields will require close collaboration between dermatologists, skin scientists and spectroscopy experts towards simplifying the technology and creating robust, rapid, easy-to-use and less expensive CRS applications.

Sensitive Skin: Assessment of the Skin Barrier Using Confocal Raman Microspectroscopy

Background/Aims: Sensitive skin (SS), a frequently reported condition in the Western world, has been suggested to be underlined by an impaired skin barrier. The aim of this study was to investigate the skin barrier molecular composition in SS subjects using confocal Raman microspectroscopy (CRS), and to compare it with that of non-SS (NSS) individuals as well as atopic dermatitis (AD) and allergic rhinoconjunctivitis (AR) subjects, who frequently report SS. Methods: Subjects with SS (n = 29), NSS (n = 30), AD (n = 11), and AR (n = 27) were included. Stratum corneum (SC) thickness, water, ceramides/fatty acids, and natural moisturizing factor (NMF) were measured by CRS along with transepidermal water loss and capacitance on the ventral forearm, thenar, and cheek. Sebum levels were additionally measured on the forearm and cheek. Results: No differences between SS and NSS subjects were found regarding SC thickness, water, and NMF content, yet a trend towards lower ceramides/fatty acids was observed in the cheek. Compared to AD subjects, the SS group showed higher ceramides/fatty acid content in the forearm, whereas no differences emerged with AR. The correlation of macroscopic biophysical techniques and CRS was weak, yet CRS confirmed the well-known lower content of NMF and water, and thinner SC in subjects with filaggrin mutations. Conclusion: The skin barrier in SS is not impaired in terms of SC thickness, water, NMF, and ceramides/fatty acid content. The failure of biophysical techniques to follow alterations in the molecular composition of the skin barrier revealed by CRS emphasizes a strong need in sensitive and specific tools for in vivo skin barrier analysis.

Responses to sodium dodecyl sulphate as an in vivo human model to study the pathomechanisms underlying sensitive skin

Hmga2 functions as a chromatin-associated factor during development, but is not expressed in most adult tissues. Expression of Hmga2 in adult tissues has been associated with a variety of human cancers. Numerous studies have implicated Hmga2 in epithelial-to-mesenchymal transition (EMT) and cancer progression through gain of function studies, but it is unclear whether Hgma2 is necessary for EMT, tumor formation or tumor progression. We deleted Hmga2 in two mouse models of squamous cell carcinoma and found this gene to be dispensable. In fact, EMT, tumor initiation and progression all appeared to be mostly unaffected by the absence of Hmga2. Tumors lacking the ability to induce Hmga2 proceeded to initiate cutaneous spindle cell and squamous cell carcinomas with all the typical pathological and molecular hallmarks of these cancers.

Measurement of skin surface biomakers by Transdermal Analyses Patch following different in vivo models of irritation: a pilot study

FibroTx Transdermal Analyses Patch (TAP) is a novel technology for non‐invasive measurements of protein biomarkers on the skin surface, in vivo. The aim of this study was to explore the potential of TAP in detecting skin surface biomarkers following mild perturbations, in vivo, using two experimental models: tape stripping, mimicking acute barrier disruption, and histamine iontophoresis, mimicking acute and local inflammation at minimal skin barrier insult.

Histamine Iontophoresis as in vivo Model to Study Human Skin Inflammation with Minimal Barrier Impairment: Pilot Study Results of Application of the Model to a Sensitive Skin Panel

Background/Aims: Histamine iontophoresis is known to elicit itch and a wheal-and-flare reaction; however, its impact on the skin barrier and underlying compartments has not been thoroughly evaluated yet. The primary objective of this study was to characterize that using immunohistochemistry, biophysical measurements, and image analysis, and secondly, to explore whether skin reactions to this model differ in sensitive skin (SS). Methods: Eighteen healthy subjects, n = 9 with SS and n = 9 with non-sensitive skin (NSS), were included based on a perception-based questionnaire. Histamine iontophoresis was performed on the buttock, and skin reactions were evaluated up to 72 h after stimulation. Results: The wheal-and-flare peaked at 30 min; after 8 h, no clinical signs were visible. No signs of disruption of the stratum corneum, as well as no increase in the number of Ki67-positive cells emerged, whereas fewer tryptase-positive mast cells and increased epidermal thickness were observed at 1 and 72 h, respectively. SS subjects showed higher perception of itch compared to NSS subjects. Conclusion: Histamine iontophoresis is a well-standardized in vivo model to quantitatively study the early stages of cutaneous inflammation with minimal impact on the skin barrier. In line with previous studies, it highlighted increased sensory perceptions in SS.

Sensitive skin and the influence of female hormone fluctuations: results from a cross-sectional digital survey in the Dutch population

BackgroundSensitive skin is a widespread condition, which is most frequently reported by women. Changing hormone levels during the menstrual cycle and menopause have been suggested among the stimuli triggering sensitive skin.ObjectivesTo investigate the perceived influence of fluctuating hormone levels on self-assessed sensitive skin, including symptoms and stimuli linked to skin sensitivity, as well as potential changes in facial and body skin and sensitive body parts, depending on hormonal status.Patients and methodsA digital questionnaire was distributed to a population of women aged 20-65 years old.ResultsA total of 278 women were included in the analysis. About 42% premenopausal women declared a perception of (increased) skin sensitivity just before and during the menstrual cycle, while this was reported by almost 32% of peri- and postmenopausal women following the menopause. The majority of reported symptoms included the presence of bumps/pimples, dryness, itching, and redness, and the majority of reported stimuli were shaving, weather, toiletries, and emotions. No differences emerged regarding characteristics of facial and body skin across different hormonal status. Significant differences in sensitivity of body parts emerged for the face and feet, reported by a larger percentage of premenopausalwomen and peri- and postmenopausalwomen, respectively.ConclusionsThe prevalence of the perceived effects of fluctuating hormone levels on self-assessed sensitive skin in women is high. These effects should be taken into consideration in skin testing and dermatological practice, and support the need for selecting personal care routine or treatment during the menstrual cycle and menopause.

Effects of blue light on inflammation and skin barrier recovery following acute perturbation. Pilot study results in healthy human subjects

While growing evidence supports the therapeutic effect of 453 nm blue light in chronic inflammatory skin diseases, data on its effects on acutely perturbed human skin are scarce. In this study, we investigated the impact of 453 nm narrow‐band LED light on healthy skin following acute perturbation.