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

2016; Wiley; Volume: 25; Issue: 5 Linguagem: Inglês

10.1111/exd.12973

1600-0625

Renée J.H. Richters, Jan C.M. Hendriks, Natallia E. Uzunbajakava, Lisanne D. Janssen, Denise Falcone, P.E.J. van Erp, P.C.M. van de Kerkhof,

Dermatology and Skin Diseases

Experimental DermatologyVolume 25, Issue 5 p. 407-409 Letter to the EditorFree Access Responses to sodium dodecyl sulphate as an in vivo human model to study the pathomechanisms underlying sensitive skin Renée J. H. Richters, Corresponding Author Renée J. H. Richters Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsCorrespondence: Renée J. H. Richters, Rene Descartesdreef 1, 6525 GL Nijmegen, The Netherlands, Tel.: 0031 (0) 24 36 13 247, Fax: 0031 (0) 24 36 35 122, e-mail: Renee.Richters@radboudumc.nlSearch for more papers by this authorJan C. M. Hendriks, Jan C. M. Hendriks Radboud Institute for Health Sciences (RIHS), Nijmegen, The NetherlandsSearch for more papers by this authorNatallia E. Uzunbajakava, Natallia E. Uzunbajakava Philips Research, Royal Philips Electronics B.V. Eindhoven, The NetherlandsSearch for more papers by this authorLisanne D. Janssen, Lisanne D. Janssen Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsSearch for more papers by this authorDenise Falcone, Denise Falcone Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsSearch for more papers by this authorPiet E. J. van Erp, Piet E. J. van Erp Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsSearch for more papers by this authorPeter C. M. van de Kerkhof, Peter C. M. van de Kerkhof Radboud Institute for Health Sciences (RIHS), Nijmegen, The NetherlandsSearch for more papers by this author Renée J. H. Richters, Corresponding Author Renée J. H. Richters Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsCorrespondence: Renée J. H. Richters, Rene Descartesdreef 1, 6525 GL Nijmegen, The Netherlands, Tel.: 0031 (0) 24 36 13 247, Fax: 0031 (0) 24 36 35 122, e-mail: Renee.Richters@radboudumc.nlSearch for more papers by this authorJan C. M. Hendriks, Jan C. M. Hendriks Radboud Institute for Health Sciences (RIHS), Nijmegen, The NetherlandsSearch for more papers by this authorNatallia E. Uzunbajakava, Natallia E. Uzunbajakava Philips Research, Royal Philips Electronics B.V. Eindhoven, The NetherlandsSearch for more papers by this authorLisanne D. Janssen, Lisanne D. Janssen Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsSearch for more papers by this authorDenise Falcone, Denise Falcone Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsSearch for more papers by this authorPiet E. J. van Erp, Piet E. J. van Erp Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The NetherlandsSearch for more papers by this authorPeter C. M. van de Kerkhof, Peter C. M. van de Kerkhof Radboud Institute for Health Sciences (RIHS), Nijmegen, The NetherlandsSearch for more papers by this author First published: 20 February 2016 https://doi.org/10.1111/exd.12973Citations: 7AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abbreviations a* CIE spectrum International Commission on Illumination, a* value denotes red/green values NSS non-sensitive skin SDS sodium dodecyl sulphate SC stratum corneum SS sensitive skin TEWL transepidermal water loss (gm−2 h−1) Introduction Sensitive skin (SS) is a poorly understood condition, in which subjects report sensations of the skin, particularly characterized by stinging, burning or itching in response-eliciting factors of different nature 1-3. Visible signs of irritation are absent in some individuals with SS. In order to detect the underlying mechanisms and eliciting factors of SS, a variety of provocative agents have been applied in clinical studies to elicit sensory skin reactions, predominantly comprising chemical substances. Sodium dodecyl sulphate (SDS) is an anionic surface active agent used as an emulsifier in pharmaceutical vehicles and cosmetics as cleansing agents, and its degenerative effects are exerted by disrupting the lipid bilayers and denaturation of stratum corneum proteins 4, 5. Previous studies showed inconsistent results with respect to differences in biophysical measurements following the application of SDS in SS subjects 6-9, and therefore, exploration of the value of surfactants in the identification of pathomechanisms of SS is required. Questions addressed More thoroughly defined design of experiment, that is evaluation of the in vivo human model under strict conditions and involving dynamic clinical, biophysical and immunohistochemical evaluation of responses, could enable the identification of potential minute differences in skin structure and composition between SS and non-sensitive (NSS) subjects. Combining these parameters in perception-based selected subjects is expected to decisively meet our objectives, that is obtaining knowledge on the role of the barrier and inflammatory mediators in pathomechanisms of SS. Experimental design Subjects with SS and NSS were selected based on recall perceptions following daily triggers (s1,2). Exclusion criteria were as follows: skin type I or IV–VI, atopy, skin diseases, immunosuppressive treatments. Subjects could not apply cosmetics for at least 24 h before the first visit until the end of participation. The study was conducted in accordance with Declaration of Helsinki principles and approved by the local ethics committee. Subjects gave written informed consent. Two sites on the buttock were exposed to 1% SDS for 24 h. Skin reactions were evaluated at baseline, directly after stimulation (‘24 h) and 48 h thereafter (‘72 h) with respect to clinical (discomfort, erythema, dryness, oedema) and biophysical parameters, comprising transepidermal water loss (TEWL) measured by AquaFlux AF200 (Biox Systems, London, UK), SC hydration by Corneometer CM825 (Courage+Khazaka electronic GmbH, Cologne, Germany) and a*value by Chroma Meter 2600d (Konica Minolta, Tokyo, Japan). Subsequently, skin punch biopsies (3 mm) were taken at each time point, which were subsequently analysed immunohistochemically by applying haematoxylin and eosin, Ki67, CD3, elastase, tryptase, S100 and CD31 antibodies (s1). Differences between the groups were analysed using a linear mixed model for repeated measurements adjusted for baseline (s1). Results Eight subjects with SS and eight subjects with NSS skin were included, and the median age (range) was 23.5 (20–32) and 22.5 (19–28) years, respectively. Six SS subjects and five NSS subjects had skin type II. Four SS and three NSS subjects reported a dry body skin. Dermographism testing was negative in all subjects. Observed medians and estimated differences between groups are presented in s2. At baseline, no statistically significant difference between SS and NSS groups was found with respect to biophysical and immunohistochemical parameters. Twenty-four hours after stimulus however, five SS and no NSS subjects showed some degree of skin dryness. At 72 h, dryness was observed in seven and three subjects, respectively. On average, the biophysical measurements were not statistically significantly different between the groups. a* values increased over time and reached maximum values for all SS subjects at 72 h after stimulus, while for NSS subjects the maximum was reached at either 24 h (n = 3) or 72 h (n = 5). With respect to skin morphology, the SC thickness decreased from baseline to 72 h after stimulus (s2). Seventy-two hours after stimulus, the SC was significantly thinner (P = 0.016) in SS subjects compared to NSS subjects (Fig. 1). This implies differences in molecular composition (e.g. amount, type and ratio of lipids and structural proteins) in the SC between the SS and NSS groups. These results confirm that the SC is vulnerable to surfactants, especially in SS. Other studies show that the SC is also vulnerable to mechanical stimulation, therefore suggesting that SS might be triggered by factors of different nature 10. As TEWL measurements were not able to discriminate between SS and NSS, it could mean that the SC structure might be malformed and establish a slightly impaired barrier at a level that is beyond sensitivity of traditional biophysical methods. Figure 1Open in figure viewerPowerPoint Mean observed values of stratum corneum thickness (Panel a) and tryptase+ mast cells per mm2 dermis (Panel b) in NSS subjects (solid bullets) and in SS subjects (open bullets) at each point of measurement. The vertical lines indicate one standard error; **P < 0.05. Note that SDS stimulation of the skin was applied to all subjects in each group up to 24 h since baseline. No statistically significant differences were found in viable epidermis thickness, proliferating keratinocytes, neutrophils, T cells, CD31, S100+ cells and spongiosis between SS and NSS subjects poststimulus (s3,4). We found, however, significantly less mast cells in SS subjects compared to NSS subjects at 24 h after stimulus (−19.5, 95% CI: (−36.7;−2.4) (P = 0.029)), (Figs 1 and 2). This finding is in line with Richters et al. studying skin responses to mechanical barrier disruption, in which a trend in a lower number of mast cells following stimulus in SS subjects was observed 10. Figure 2Open in figure viewerPowerPoint Representative images of tryptase stainings (400× magnification) at baseline, 24 and 72 h after stimulus for NSS subjects (Panel a) and SS subjects (Panel b), showing that mean mast cell numbers were slightly lower in SS subjects compared to NSS subjects at all time points, reaching significant levels at 24 h (P < 0.05). A significant increase at 24 h could be observed compared to baseline, and a significant decrease compared to 72 h after stimulus. Conclusions The questionnaire seems to adequately distinguish SS from NSS subjects. Although not as abundant as tape stripping, this mild stimulus holding a yet complimentary mode of action elicits different skin responses between SS and NSS groups, thus confirming that SS can be caused by triggers of different nature. SS subjects were found to report higher dryness, show more redness, more thinning of the SC and lower mast cell count after SDS application. A limitation is the small population. Because we use a functional marker for mast cells, tryptase, we could have underestimated the number of mast cells in SS subjects, due to undetectable degranulated mast cells by immunohistochemical analysis. We hypothesize that mast cells in SS subjects have either been degranulated already in response to the stimulus or do not migrate that extensively to the challenged skin site. The latter could be caused by a secondary increase in reaction thresholds, to prevent unpleasant skin sensations at continuously following very mild skin challenges. TEWL and SC hydration seem to be of limited value in the identification of SS. In line with our previous recommendations, we propose that research efforts for understanding pathomechanisms of SS should be directed at studying SC and immune responses. Acknowledgements The authors thank Wim Verkruijsse, principal scientist, Philips Research, Eindhoven, the Netherlands; and Jan Willem Bikker, statistical consultant, CQM consultancy, Eindhoven, the Netherlands. Author contributions Wim Verkruijsse (principal scientist, Philips Research, Eindhoven, the Netherlands) contributed to the design of the research study, is an employee of Royal Philips Electronics B.V., the Netherlands, and has no conflict of interest to declare. Jan Willem Bikker (statistical consultant, CQM consultancy, Eindhoven, the Netherlands) assisted in the analysis of questionnaire data, which were used to select subjects with sensitive skin and subjects with non-sensitive skin, and has no conflict of interest to declare. Funding and disclosures The costs made to conduct this study were paid by Royal Philips Electronics B.V, the Netherlands Natallia Uzunbajakava is an employee of Royal Philips Electronics B.V, the Netherlands and received salary for this study. Supporting Information Filename Description exd12973-sup-0001-DataS1-S3.docxWord document, 26.2 KB Data S1. Methods and material.Data S3. Supplementary References. exd12973-sup-0002-DataS2.docWord document, 288 KB Data S2. Questionnaire. exd12973-sup-0003-FigureS1.docxWord document, 32.5 KB Figure S1. Representative images of clinical presentation and immunohistochemistry. exd12973-sup-0004-TableS1.docxWord document, 27.6 MB Table S1. The observed median (range) of the biophysical measurements and the immunohistochemical markers and the estimated mean differences (95% CI) at each point of measurement by skin sensitivity, using a linear mixed model for repeated measurements adjusted for baseline values. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Misery L, Myon E, Martin N et al. J Eur Acad Dermatol Venereol 2007: 21: 620– 628. 2Morizot F, Guinot C, Lopez J et al. Cosmet Toiletries 2000: 115: 83– 89. 3Saint-Martory C, Roguedas-Contios A M, Sibaud V et al. Br J Dermatol 2008: 158: 130– 133. 4Fartasch M. Microsc Res Tech 1997: 37: 193– 199. 5Willis C M, Stephens C J M, Wilkinson J D. J Investig Dermatol 1989: 93: 695– 699. 6Cho H J, Chung B Y, Lee H B et al. J Dermatol 2012: 39: 295– 300. 7Diogo L, Papoila A L. Skin Res Technol 2010: 16: 30– 37. 8Loffler H, Dickel H, Kuss O et al. Acta Dermato-Venereologica 2001: 81: 343– 346. 9Robinson M K, Perkins M A. Contact Dermatitis 2001: 45: 205– 213. 10Richters R J, Uzunbajakava N E, Falcone D et al. Br J Dermatol 2015: doi: 10.1111/bjd.14307 [e-pub ahead of print] Citing Literature Volume25, Issue5May 2016Pages 407-409 FiguresReferencesRelatedInformation