Depth-dependent hydration dynamics in human skin: Vehicle-controlled efficacy assessment of a functional 10% urea plus NMF moisturizer by near-infrared confocal spectroscopic imaging (KOSIM IR) and capacitance method complemented by volunteer perception.

BACKGROUND: Stratum corneum (SC) hydration is vital for the optimal maintenance and appearance of healthy skin. In this context, we evaluated the efficacy of an NMF-enriched moisturizer containing 10% urea on different aspects of SC hydration of dry skin. MATERIAL AND METHODS: In two clinical studies, the hydration efficacy of the moisturizer in comparison to its vehicle was investigated. In the first study, 42 subjects applied the moisturizer and the vehicle to one lower leg each. Thirty minutes and 24 h after this single treatment, SC hydration was measured by corneometry. Volunteers also rated skin moisturization and evaluated product properties. In the second study, 27 subjects each treated one forearm twice daily for 2 weeks with the moisturizer and the vehicle. Then, depth-resolved water-absorption spectra were measured by near-infrared confocal spectroscopic imaging (KOSIM IR). RESULTS: The moisturizer exerted a superior hydrating effect compared to the vehicle. KOSIM IR measurements show that, compared to the vehicle, the moisturizer significantly improved the water gradient in the SC from the surface to a depth of 15 µm. Moreover, the moisturizer received high acceptance ratings from the volunteers and was preferred to the vehicle. CONCLUSION: The humectants applied in the investigated moisturizer improved SC water content in total and as a function of depth. The combination of depth-resolved data (KOSIM IR) with classical corneometry provides an integrated concept in the measurement of skin hydration, rendering both methods complementary. These findings were in line with the volunteers` self-assessments of the moisturizer properties that are relevant to treatment adherence.

A Biomimetic Combination of Actives Enhances Skin Hydration and Barrier Function via Modulation of Gene Expression: Results of Two Double-Blind, Vehicle-Controlled Clinical Studies.

INTRODUCTION: Xerosis cutis is characterized by a decreased stratum corneum (SC) hydration and an impaired skin barrier function. Urea, the most prevalent natural moisturizing factor (NMF), is currently considered the gold standard. Its efficacy can further be increased by combining urea with other NMF and skin barrier lipids (SBLs). OBJECTIVE: We set out to evaluate physiological effects of a novel functional moisturizer containing 10% urea, additional NMF components, and a combination of SBLs on skin hydration and skin barrier integrity on a cellular and phenotypic level in female volunteers suffering from xerosis. METHODS: Two double-blind, vehicle-controlled clinical studies were conducted. In the first study, 44 female subjects having very dry body skin applied the moisturizer or its vehicle twice daily to their volar forearms. Twenty-four hours after a single product application as well as 24 h after 2 weeks of treatment, SC hydration was measured by corneometry. Skin barrier function was assessed by transepidermal water loss 24 h and 48 h after 2 weeks of regular use. Twenty-four hours after 2 weeks of application, skin tape stripping was performed, and urea content was determined in the 3rd strip by means of high-performance liquid chromatography/tandem mass spectrometry. In the second study, 22 women with self-reported very dry skin applied the moisturizer or vehicle twice daily to their volar forearms for 2 weeks. Then, suction blister samples were obtained for gene expression analysis using RT-PCR. RESULTS: Application of the actives led to significantly improved skin hydration and barrier function at all points in time. Compared to the vehicle, application of the moisturizer for 2 weeks resulted in a significant increase in SC urea content. Relative gene expression data revealed significant upregulation of genes associated with skin barrier function, hydration, differentiation, and lipid metabolism compared to the vehicle-treated area. CONCLUSIONS: Overall, our data demonstrate that the functional moisturizer provides an adequate bioavailability of urea and a beneficial biophysical impact on xerotic skin. Topical treatment with a combination of urea and additional NMF as well as SBL can modify mRNA expression of important epidermal genes stimulating cellular processes and functions. The well-tolerated novel functional moisturizer stimulates molecular mechanisms involved in skin hydration and barrier function and is a profoundly effective treatment option for xerosis cutis.

Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical Steroid Treatment in Atopic Dermatitis: A Double-blind, Randomized, Vehicle-controlled, Left-right Comparison Study.

Prevention of the flares is a main goal in the long-term treatment of atopic dermatitis (AD). Therefore we investigated the efficacy of a water-in-oil emollient, containing licochalcone A, omega-6-fatty acids, ceramide 3 and glycerol, for prevention of the flares in adults with mild to moderately severe AD, treated with topical steroids, that led to clearing of the inflammatory lesions and had been discontinued prior to inclusion. The study was a 12-week, double-blind, randomized, vehicle-controlled, left-right comparison test with the number of relapses, defined as re-occurrence of erythema for at least 3 consecutive days, considered the primary outcome. Compared with the vehicle, the active formulation significantly reduced the number of relapses and maintained the barrier homeostasis of the respective arm. To the best of knowledge, this is the first study to show prevention of the AD flares by the use of stand-alone emollient treatment, based on comparison with the corresponding vehicle while excluding concomitant/rescue medications.

Impact of a pH 5 Oil-in-Water Emulsion on Skin Surface pH.

BACKGROUND: Human skin surface has a physiologically acidic pH (pHss). In cases of increased pHss, the acidity of the skin can be restored by topical formulations. We tested a pH 5 oil-in-water (O/W) emulsion for pHss regeneration and stabilization. METHODS: We performed 2 experiments with 10 female study subjects in each. In both experiments, 2D imaging with luminescent sensor foils was used to determine pHss. Alkalization was reached by washing the volar forearm with a soap bar and warm running tap water for 20 min. Experiment 1: after defining the baseline pHss, we alkalized the respective area and measured pHss over a duration of 5 h, while applying emulsion every hour. Experiment 2: study subjects used the emulsion twice daily for 1 week. Then, pHss was measured before and after 5 min of washing a treated and an untreated area on the volar forearm. RESULTS: (1) 5 h after alkalization, the treated arm showed a significantly lower pHss than the untreated one (5.87 ± 0.03 vs. 6.05 ± 0.03); (2) after washing, the treated area had a significantly lower pHss than controls (6.13 ± 0.03 vs. 6.27 ± 0.05). CONCLUSIONS: The tested pH 5 O/W emulsion seems to improve regeneration and stabilization of pHss.

Prevention of Cutaneous Penetration and CD1c+ Uptake of Pollen Allergens by a Barrier-Enhancing Formulation.

Recent studies have shown that pollen proteins can penetrate the impaired skin barrier of atopic patients and exacerbate their disease. In the presented study the effect of a topically applied barrier-enhancing formulation was investigated for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal cells. The pollen proteins were fluorescence labelled and applied on barrier-disrupted excised human skin. CD1c+ cells were selected after magnetic cell sorting and analysed using laser scanning microscopy. In untreated disrupted skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an uptake of pollen allergens. These results encourage the treatment of atopic patients with barrier-enhancing formulations to reduce the impact of pollen on air-exposed skin areas and hence the exacerbation of cutaneous symptoms.

Highly efficient and compatible shampoo for use after hair transplant.

BACKGROUND: Sensitive or hyperreactive skin is a common condition defined by prickling, burning, pain, and pruritus. Although this skin problem was initially described on the face, the scalp is often affected. A sensitive scalp can react with irritation to harsh surfactants or other additives which are often present in shampoos. For this reason, we developed a new rinse-off hypertolerant shampoo specifically designed for the hypersensitive and problematic scalp. METHODS: The shampoo formulation is based on an extremely mild surfactant system and contains bisabolol, an anti-irritant and anti-inflammatory ingredient of chamomile. The shampoo is free of additives such as perfumes, silicones, colorants, parabens, paraffins, and betaine. Since skin can remain in a hyperreactive state after wounding, the status after hair transplantation was chosen as a model system to test the shampoo. Scalp condition and compatibility of each volunteer were analyzed by a plastic surgeon directly after hair transplant and after stitch removal. The plastic surgeons also rated whether they would recommend the further use of the test shampoo. Additionally, volunteers completed a self-assessment questionnaire. RESULTS: Following hair transplantation, regular use of the shampoo resulted in a significant reduction in the extent of scabbing and erythema. This was confirmed by dermatological scalp examinations performed by the plastic surgeon as well as in volunteers' self-assessments. The plastic surgeon highly recommended the further use of the test shampoo after hair transplant to all study participants. CONCLUSION: Application of the test shampoo demonstrated excellent skin compatibility and product efficacy after hair transplant. The test shampoo significantly reduced the extent of scabs and erythema. Therefore, the shampoo is ideally suited for use after hair transplantation and for the treatment of sensitive scalp. The excellent skin compatibility is because of the mild surfactant system, the calming ingredient bisabolol, and the absence of potentially irritating ingredients.

Steroid-Free Over-the-Counter Eczema Skin Care Formulations Reduce Risk of Flare, Prolong Time to Flare, and Reduce Eczema Symptoms in Pediatric Subjects With Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic skin condition associated with decreased barrier function resulting in periodic flare-ups of erythematous and pruritic lesions. Guidelines recommend daily treatment of atopic skin with emollient moisturizers for prevention of flares and maintenance of the flare-free state. This study evaluated the efficacy of 2 steroid-free, nonprescription eczema skin care formulations for reducing the risk of flare and relieving symptoms in infants and children with AD: Body Cream for the daily maintenance treatment of atopic skin and Flare Treatment for the treatment of atopic flares. METHODS: After a 2-week washout period, subjects (N=45; mean age 3.5 years) were randomized to cleanser plus daily moisturizing with Body Cream (moisturizer group) or cleanser only (control group) for 6 months or until flare. Subjects experiencing flare received Flare Treatment for 4 weeks. RESULTS: The incidence of flare was significantly lower in the moisturizer group compared with the control group (21% vs 65%; P=.006), while the median time to flare was shorter in the control group (28 vs >180 days). Risk of flare was reduced by 44.1% after 6 months of Body Cream application. Flare Treatment reduced overall eczema symptom severity at week 2 and week 4; 78.9% of flares had improved or cleared at week 4. CONCLUSIONS: Body Cream reduced the incidence of flare and the time to flare, reinforcing guidelines that daily emollient therapy should be an integral part of the maintenance treatment plan for the prevention of disease flares. Body Cream and Flare Treatment are effective over-the-counter steroid-free options for management of AD in children.

Efficacy and Tolerability of Steroid-Free, Over-the-Counter Treatment Formulations in Infants and Children With Atopic Dermatitis.

BACKGROUND: Two steroid-free, over-the-counter skin protectant products have been developed for the care and treatment of atopic dermatitis (AD)-Eucerin Eczema Relief Body Crème (Body Cream) for daily skin moisturization and Eucerin Eczema Relief Instant Therapy cream (Instant Therapy) for treatment of AD flare-ups. We tested the efficacy and tolerability of these formulations in infants and children with AD. METHODS: Study 1: Body Cream was applied twice daily to the lower legs of 64 children with a history of AD (aged 3 months to 12 years) for 14 days. Study 2: Instant Therapy was applied to active lesions and surrounding skin of 29 children (aged 3 months to 12 years) with active atopic lesions. Assessments were performed at baseline and Days 7 and 14. Symptoms were assessed using the Atopic Dermatitis Severity Index in Study 2. RESULTS: Body Cream significantly improved skin hydration and reduced itching, burning/stinging, erythema, and tactile roughness. Instant Therapy significantly improved skin hydration and AD symptoms, notably pruritus, erythema, and lichenification. Both products were safe and well tolerated. DISCUSSION: Body Cream and Instant Therapy were effective and well tolerated in the treatment of AD in children. These products provide steroid-free, nonprescription therapy for the maintenance and treatment of acute eczema and were proven effective and safe in infants as young as 3 months.

Steroid-free emollient formulations reduce symptoms of eczema and improve quality of life.

Two over-the-counter products have been clinically tested for efficacy and tolerability in the treatment of atopic dermatitis. Study 1 evaluated a daily maintenance Body Cream (Eucerin Eczema Relief Body Crème) applied twice daily for 14 days, followed by treatment withdrawal for 5 days (regression period) in subjects with a history of atopic dermatitis. Study 2 evaluated an acute treatment (Eucerin Eczema Relief Instant Therapy [Instant Therapy]) for active atopic dermatitis lesions administered for 14 days. Skin barrier function, hydration, tolerability, and relief of symptoms were assessed at baseline, day 7, and day 14. Study 2 also measured itch relief and treatment impact on work, social activities, and sleep. Body Cream significantly improved skin hydration and barrier function (P<.001) at 14 days, with improvements persisting through the 5-day regression phase. Itching was significantly improved in 93.8% of subjects (P<.001). Instant Therapy treatment of atopic dermatitis lesions significantly improved skin hydration and barrier function, as well as symptoms of erythema, pruritus, excoriation, and lichenification, with rapid improvement of itch reported within minutes of the first treatment application. Instant Therapy significantly reduced itch intensity and frequency, and demonstrated beneficial improvements in subjects' quality of life. Body Cream and Instant Therapy were both safe and well tolerated.

Efficacy of a new tonic containing urea, lactate, polidocanol, and glycyrrhiza inflata root extract in the treatment of a dry, itchy, and subclinically inflamed scalp.

BACKGROUND/AIMS: Dry, itchy and inflamed scalp conditions are common and often associated with diseases such as atopic dermatitis or psoriasis. To improve these symptoms, we investigated the efficacy of a new tonic containing the active ingredients urea, lactate, polidocanol, and Glycyrrhiza inflata root extract, containing licochalcone A. STUDY DESIGN/METHODS: 30 subjects with dry and itchy scalp conditions underwent a randomized half-head study for 4 weeks, applying the leave-on tonic three times a week on one side of the scalp. Tonic effects on skin hydration, itching, lipids, microinflammation, and substantivity of tonic compounds were determined using corneometry, middle-infrared spectroscopy, direct analysis in real-time mass spectrometry, and enzyme-linked immunosorbent assay. Volunteers performed a self-assessment; changes in scalp condition were documented by in vivo microscopy. RESULTS: After tonic treatment, scalp moisture was significantly increased, whereas scalp itching and tautness were significantly reduced. Results also demonstrated a high substantivity of urea and lactate on the scalp, an increase in triglyceride, and a decrease in free fatty acid levels. The amount of total lipids was unchanged. Analyses of scalp wash-ups verified a significant reduction in important pro-inflammatory markers. CONCLUSION: Due to the actives urea, lactate, polidocanol, and the anti-inflammatory licochalcone A, the new scalp tonic exhibited excellent performance in alleviating scalp dryness, itching, microinflammation, and in normalizing disturbances of scalp lipids.

Treatment of xerosis with a topical formulation containing glyceryl glucoside, natural moisturizing factors, and ceramide.

OBJECTIVE: To assess the effects of Light Formulation, an oil-in-water emulsion, and Rich Formulation, a water-in-oil emulsion, for the treatment of xerosis. DESIGN: Two double-blind, vehicle-controlled trials (both formulations); a double-blind, randomized regression study (Rich Formulation); and a single-blind tolerability study (Light Formulation). The two formulations were applied twice daily for two weeks, for five days in the regression study, and twice daily for two weeks in the tolerability study. SETTING: Studies were conducted during winter in Hamburg, Germany. PARTICIPANTS: A total of 169 subjects were enrolled and 154 completed the studies. The majority were between 50 and 80 years of age, women, all with very dry skin. One withdrew because of an incompatibility reaction that reoccurred with the subject's own body lotion after sun exposure. MEASUREMENTS: Skin hydration and skin barrier function with both formulations over two weeks, long-term moisturization effect after discontinuation of Rich Formulation, and symptom improvement and skin tolerability with Light Formulation. RESULTS: Vehicle-controlled studies of Light and Rich Formulations demonstrated significantly improved hydration at Weeks 1 and 2 versus the untreated site and vehicles, and significantly reduced transepidermal water loss versus untreated site and basic vehicle. Both products significantly decreased visible dryness and tactile roughness. In the regression study, Rich Formulation maintained significant moisturization six days after treatment discontinuation. Light Formulation reduced symptoms of itching, burning, tightness, tingling, and feeling of dryness. CONCLUSION: These formulations represent a new approach for the treatment of xerosis by addressing multiple key deficiencies in skin hydration.

Comparison of two in vitro models for the analysis of follicular penetration and its prevention by barrier emulsions.

The penetration of topically applied substances in and through the human skin is of special interest for the development and optimization of topically applied drugs and cosmetic products. In the present study, the efficacy of barrier emulsions in the prevention of the penetration of pollen allergens into the hair follicles was investigated. Because of the sensitising potential of the used pollen allergens, the study was carried out under in vitro conditions. Therefore, excised human skin and porcine ear skin were used as tissue models. Applying laser-scanning microscopy and fluorescent-labeled grass pollen allergens, we found that the preventive efficacy of the barrier emulsions could be significantly better investigated on porcine ear skin than on excised human skin. This might be due to the contraction of the elastic fibres around the hair follicles in excised human skin after its removal. In contrast to the excised human skin, the porcine ear skin remains on the cartilage during the experiment. Therefore, contraction of the tissue can be avoided. The results give further indication that in vitro studies based on membranes of excised skin are not suitable for the investigation of the follicular penetration pathway of topically applied substances.

Skin-lightening effects of a new face care product in patients with melasma.

BACKGROUND: Melasma is a common pigmentation disorder having considerable effect on patients' emotional and psychological well-being. OBJECTIVE: Assessment of efficacy and tolerability of a new face care product for the targeted spot treatment of darker pigmented areas in subjects with melasma and evaluation of effects on patients' quality of life. METHODS: Twenty subjects with melasma were enrolled in this study. Data of 19 participants were available for analysis. Melasma severity was evaluated at baseline, after 4 weeks, and after 8 weeks by using the Melasma Area and Severity Index (MASI). Furthermore, chromametry and digital image analysis of videomicroscopic photographs were performed, and quality of life was measured using the Melasma Quality of Life Scale. RESULTS: The application of the product resulted in a significant lightening of melasma in comparison with baseline and to untreated control areas. The MASI score dropped by more than 40% after 8 weeks. Measurement of skin color by chromametry revealed lightening of pigmented areas and a significant decrease in contrast between melasma and normal-pigmented surrounding skin. These results were confirmed by digital image analysis. Tolerability of the product was rated to be excellent, and patients experienced a significant gain in quality of life. CONCLUSION: The data demonstrate that the new face care product is effective and highly skin tolerable and clearly improves quality of life of patients with melasma.