JOURNAL OF COSMETIC SCIENCE 80 Sensitive skin is very frequent. In France, approximately 50% of individuals (59% of women and 41% of men) report having reactive skin (9). This patient-reported preva- lence varies little across European countries (10), the United States of America (11), and Japan (12). Sensitive skin is clearly a very frequent cosmetic problem. Although the appearance of this kind of skin is normal in most cases, sensitive skin may occur in individuals who have another skin disorder (e.g., atopic dermatitis, seborrheic derma- titis, or rosacea) (9). The association with ethnicity is controversial (3,4,13). Three large epidemiological studies reported no “racial” differences when reporting sensitiv- ity (11,14,15), most likely because races or ethnicities do not exist (16). On the other hand, cultural factors (10–12) are most likely crucial for defi ning sensitive skin, related symptoms, and lifestyle factors that may favor several triggering factors. For example, Japanese women react more intensely than German women, even though there is no difference in the sensory innervation of their skin (17). The role of phototype has also been suggested (18). The debate is still out on how to treat sensitive skin. Using well-tolerated cosmetics or cosmetics with soothing effects, which decrease skin reactivity to insults, is recom- mended. In this study, we tested a cream made up of different compounds. Our aims were to have well tolerance, limit neurogenic and keratinocyte-induced infl amma- tion, and reinforce skin barrier function in two different environments and on differ- ent ethnic skin (France and Thailand). Preliminary biological studies were also presented. PATIENTS AND METHODS PRODUCT The tested cosmetic product (Sensibio Tolérance +®) is a cream containing sodium PCA (sodium l-pyrrolidone carboxylate 1%) and Neurocontrol® (1.25%), a combination of RMX (rhamnose, mannitol, and xylitol, which are three carbohydrates) and a tetrapep- tide [a transient receptor potential V1 (TRPV1) inhibitor]. In vitro studies. Human normal keratinocytes (HNK) from 3 different donors (Lonza, Belgium) were cultured (65,000 cells/well) with KBM [(keratinocyte basal medium) Lonza] and BPE (bovine pituitary extract), hEGF (human Epidermal Growth Factor), insulin, hydrocortisone, gentamicin, amphotericin B, epinephrine, and transferrin. The following day, the culture medium was replaced by the same medium supplemented or not with tested molecules (rhamnose, mannitol, xylitol and their association). After a 1-h incubation, tumor necrosis factor-α (TNF-α) (50 ng/ml) was added to induce interleukin 8 (IL-8) synthesis. After 24-h incubation, IL-8 amounts were measured by enzyme-linked immu- nosorbent assay (ELISA) (R&D Systems, Bristol, UK). Clinical studies. The primary objective was to evaluate the preventive soothing effect. The secondary objectives were to evaluate the immediate soothing effect, product tolerance, and its impact on quality of life. The studies were performed by Dermscan in France and Thailand under the same con- ditions, with the same cosmetic product. Inclusion criteria were women aged 18 years or older, an I-II-III-IV phototype (Fitzpatrick scale), sensitive skin on their face, a

NEW TOPICAL COMBINATION ON SENSITIVE SKIN 81 stinging test score 3, and patient consent. Exclusion criteria were: skin disease, known allergies, treatment for pain or itchiness, and the current application of another skin product or UV exposure. The stinging test (19) was performed by applying 10% lactic acid (Sigma-Aldrich, Saint-Quentin-Fallavier, France) on one nasolabial fold and saline (Gifrer) on the other for 10 min. Each minute, the patient noted the intensity of unpleasant sensations using a four-point scale: none = 0, slight = 1, moderate = 2, severe = 3. The stinging score was calculated by adding scores taken after 2.5 min and 5 min of lactic acid application to the area. A score of 3/6 or higher was necessary for inclusion in the study. The stinging test was also used to evaluate the preventive effect on these pa- tients by measuring the stinging score before treatment and after 4 weeks with two applications of the cream a day. An erythema score (from 0 to 4) was also used after the stinging test. To assess the immediate soothing effect, the stinging score was evaluated 2 min after applying a 10% lactic acid solution. Then, the product was applied and a stinging score was evaluated 5 and 15 min after this application. Product tolerance was assessed by evaluating many criteria before treatment and after 4 weeks of treatment: edema, dryness, desquamation, roughness, vesicles, twinging, tin- gling, itchiness, or burning (none, very slight, slight, moderate, or severe). Quality of life was evaluated using the Dermatology Life Quality Index (DLQI) be- fore treatment and after 4 weeks of treatment. The DLQI is a health quality of life scale specifi cally designed for dermatological disorders (20). It includes 10 items, which focus on 6 dimensions: “symptoms,” “daily activities,” “leisure,” “work,” “per- sonal relationships,” and “treatment.” A total score (between 0 and 30) is calculated and can be expressed as a percentage. The higher the score, the more quality of life is impaired. The health quality of life is considered “impaired” with a score of 6. It is “very impaired” with a score of 11. And it is “extremely impaired” with a score of 21 or greater (21). Capsaicin and SLS Tests. This part of the study was performed in Poland by Dermscan (Ul. Kruczkowskiego 12, 80–288 Gdansk). A capsaicin test was performed on women with dry and sensitive skin. After washing their nasogenian folds with 10% ethanol, increasing concentrations of capsaicin (from 10−3% to 10−4%) and 10% ethanol on the other fold were applied. Patients evaluated abnormal sensations on a scale from 0 to 5. A second evaluation was performed after 28 days by applying Sensibio Tolérance +® (Bioderma, Lyon, France) cream twice a day. A sodium lauryl sulfate (SLS) test was performed by comparing the effects of (i) Sensibio Tolérance+® and 1% SLS, (ii) placebo, and (iii) placebo and 1% SLS. Placebo was a usual neutral basis made with water, glycerin, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, isohexadecane, titanium dioxide, phenoxyethanol, chlorphenesin, polysorbate 60, alumina, and stearic acid. Skin color was measured using Chromameter® (Konica Minolta, Singapore). Then, patch-tests were applied to normal forearm skin for 18 h. After removing the patches, the skin was washed and a new measurement was taken at 24 h. Statistical analysis. Statistical analyses were performed using a t-test (Mann–Whitney test), a Student test, a Shapiro–Wilk test, and a Wilcoxon test, according to the quality of the data. Excel 2010 and SAS9.2 (SAS Institute, Cary, NC) softwares were used.