N.E. Uzunbajakava

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.

Improved depth resolution in near-infrared diffuse reflectance spectroscopy using obliquely oriented fibers

We demonstrate a significant improvement of depth selectivity when using obliquely oriented fibers for near-infrared (NIR) diffuse reflectance spectroscopy. This is confirmed by diffuse reflectance measurements of a two-layer tissue-mimicking phantom across the spectral range from 1,000 to 1,940 nm. The experimental proof is supported by Monte Carlo simulations. The results reveal up to fourfold reduction in the mean optical penetration depth, twofold reduction in its variation, and a decrease in the number of scattering events when a single fiber is oriented at an angle of 60 deg. The effect of reducing the mean optical penetration depth is enhanced by orienting both fibers inwardly. Using outwardly oriented fibers enables more selective probing of deeper layers, while reducing the contribution from surface layers. We further demonstrate that the effect of an inward oblique arrangement can be approximated to a decrease in fiber-to-fiber separation in the case of a perpendicular fiber arrangement. This approximation is valid in the weak- or absorption-free regime. Our results assert the advantages of using obliquely oriented fibers when attempting to specifically address superficial tissue layers, for example, for skin cancer detection, or in noninvasive glucose monitoring. Such flexibility could be further advantageous in a range of minimally invasive applications, including catheter-based interventions.

Photobiomodulation devices for hair regrowth and wound healing: a therapy full of promise but a literature full of confusion.

Photobiomodulation is reported to positively influence hair regrowth, wound healing, skin rejuvenation and psoriasis. Despite rapid translation of this science to commercial therapeutic solutions, significant gaps in our understanding of the underlying processes remain. The aim of this review was to seek greater clarity and rationality specifically for the selection of optical parameters for studies on hair regrowth and wound healing. Our investigation of 90 reports published between 1985 and 2015 revealed major inconsistencies in optical parameters selected for clinical applications. Moreover, poorly understood photoreceptors expressed in skin such as cytochrome c oxidase, cryptochromes, opsins etc. may trigger different molecular mechanisms. All this could explain the plethora of reported physiological effects of light. To derive parameters for optimal clinical efficacy of photobiomodulation, we recommend a more rational approach to underpin clinical studies, with research on molecular targets and pathways using well‐defined biological model systems to enable translation of optical parameters from in vitro to in vivo. Furthermore, special attention needs to be paid when conducting studies for hair regrowth, aiming for double‐blind, placebo‐controlled randomized clinical trials as the gold standard for quantifying hair growth.

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.

Optical properties of the medulla and the cortex of human scalp hair

An increasing number of applications, including non- or minimally invasive diagnostics and treatment as well as various cosmetic procedures, has resulted in a need to determine the optical properties of hair and its structures. We report on the measurement of the total attenuation coefficient of the cortex and the medulla of blond, gray, and Asian black human scalp hair at a 633-nm wavelength. Our results show that for blond and gray hair the total attenuation coefficient of the medulla is more than 200 times higher compared to that of the cortex. This difference is only 1.5 times for Asian black hair. Furthermore, we present the total attenuation coefficient of the cortex of blond, gray, light brown, and Asian black hair measured at wavelengths of 409, 532, 633, 800, and 1064 nm. The total attenuation coefficient consistently decreases with an increase in wavelength, as well as with a decrease in hair pigmentation. Additionally, we demonstrate the dependence of the total attenuation coefficient of the cortex and the medulla of Asian black hair on the polarization of incident light. A similar dependence is observed for the cortex of blond and gray hair but not for the medulla of these hair types.

A new path in defining light parameters for hair growth: discovery and modulation of photoreceptors in human hair follicle

Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light‐sensitive receptors in the human hair follicle and to study the impact of UV‐free blue light on hair growth ex vivo.

Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome

Photobiomodulation-based (LLLT) therapies show tantalizing promise for treatment of skin diseases. Confidence in this approach is blighted however by lamentable inconsistency in published experimental designs, and so complicates interpretation. Here we interrogate the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.g., serum concentration, cell confluency, medium refreshment, direct/indirect treatment, oxygen concentration, etc.), in primary cultures of normal human dermal fibroblasts exposed to visible and near infra-red (NIR) light. Apart from irradiance, all study parameters impacted significantly on fibroblast metabolic activity. Moreover, when cells were grown at atmospheric O2 levels (i.e. 20%) short wavelength light inhibited cell metabolism, while negligible effects were seen with long visible and NIR wavelength. By contrast, NIR stimulated cells when exposed to dermal tissue oxygen levels (approx. 2%). The impact of culture conditions was further seen when inhibitory effects of short wavelength light were reduced with increasing serum concentration and cell confluency. We conclude that a significant source of problematic interpretations in photobiomodulation reports derives from poor optimization of study design. Further development of this field using in vitro/ex vivo models should embrace significant standardization of study design, ideally within a design-of-experiment setting.

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.