Ethanol-Based Disinfectants Containing Urea May Reduce Soap Sensitivity.

BACKGROUND: The use of disinfectants is crucial to preventing the spread of nosocomial infections in health care workers. As many as 25 applications of hand disinfectants is a realistic default value during a working day. However, alcohol-based hand disinfectants may weaken skin barrier function and induce dryness and eczema, which decrease their acceptance. OBJECTIVE: To evaluate the effect of ethanol-containing disinfectants with 5% urea on skin barrier function and on sensitivity to an irritant soap (sodium lauryl sulfate [SLS]). METHODS: Twenty healthy volunteers treated one of their forearms twice daily for 17 days with an ethanol-containing gel with 5% urea. Two types of gels with urea were tested. Treatment was randomized to left or right forearm, and the contralateral forearm served as untreated control. Transepidermal water loss, skin capacitance (dryness), and sensitivity to SLS were evaluated. RESULTS: Twice-daily application of the urea-containing ethanol gels lowered transepidermal water loss, prevented dryness, and reduced sensitivity to SLS compared with the untreated control skin. CONCLUSIONS: Improved barrier function using this ethanol gel with urea may have relevance in daily disinfectant procedures.

The revised EEMCO guidance for the in vivo measurement of water in the skin.

BACKGROUND: Noninvasive quantification of stratum corneum water content is widely used in skin research and topical product development. METHODS: The original EEMCO guidelines on measurements of skin hydration by electrical methods and transepidermal water loss (TEWL) by evaporimeter published in 1997 and 2001 have been revisited and updated with the incorporation of recently available technologies. RESULTS: Electrical methods and open-chamber evaporimeters for measurement of TEWL are still the preferred techniques to measure the water balance in the stratum corneum. The background technology and biophysics of these instruments remain relevant and valid. However, new methods that can image surface hydration and measure depth profiles of dermal water content now available. Open-chamber measurement of TEWL has been supplemented with semiopen and closed chamber probes, which are more robust to environmental influence and therefore convenient to use and more applicable to field studies. However, closed chamber methods interfere with the evaporation of water, and the methods cannot be used for continuous monitoring. Validation of methods with respect to intra- and inter-instrument variation remains challenging. No validation standard or test phantom is available. RESULTS AND CONCLUSIONS: The established methods for measurement of epidermal water content and TEWL have been supplemented with important new technologies including methods that allow imaging of epidermal water distribution and water depth profiles. A much more complete and sophisticated characterization of the various aspects of the dermal water barrier has been accomplished by means of today's noninvasive techniques; however, instrument standardization and validation remain a challenge.

Treatments Improving Skin Barrier Function.

Moisturizers affect the stratum corneum architecture and barrier homeostasis, i.e. topically applied ingredients are not as inert to the skin as one might expect. A number of different mechanisms behind the barrier-influencing effects of moisturizers have been suggested, such as simple deposition of lipid material outside the skin. Ingredients in the moisturizers may also change the lamellar organization and the packing of the lipid matrix and thereby skin permeability. Topically applied substances may also penetrate deeper into the skin and interfere with the production of barrier lipids and the maturation of corneocytes. Furthermore, moisturizing creams may influence the desquamatory proteases and alter the thickness of the stratum corneum.

Comparison of Moisturizing Creams for the Prevention of Atopic Dermatitis Relapse: A Randomized Double-blind Controlled Multicentre Clinical Trial.

Atopic dermatitis (AD) affects adults and children and has a negative impact on quality of life. The present multicentre randomized double-blind controlled trial showed a barrier-improving cream (5% urea) to be superior to a reference cream in preventing eczema relapse in patients with AD (hazard ratio 0.634, p = 0.011). The risk of eczema relapse was reduced by 37% (95% confidence interval (95% CI) 10-55%). Median time to relapse in the test cream group and in the reference cream group was 22 days and 15 days, respectively (p = 0.013). At 6 months 26% of the patients in the test cream group were still eczema free, compared with 10% in the reference cream group. Thus, the barrier-improving cream significantly prolonged the eczema-free time compared with the reference cream and decreased the risk of eczema relapse. The test cream was well tolerated in patients with AD.

The influence of a humectant-rich mixture on normalz skin barrier function and on once- and twice-daily treatment of foot xerosis. A prospective, randomized, evaluator-blind, bilateral and untreated-control study.

BACKGROUND: Moisturizers are often used to overcome dry skin conditions. However, cosmetic moisturizers may lack in efficiency and may also deteriorate skin barrier function. The objective of this study was to generate data on a new humectant-rich formulation (15% alfahydroxy acids and 15% urea) in the treatment of normal skin as well as in dry feet with hyperkeratosis and cracked skin with fissures. Changes in permeability and effectiveness of the product after once- and twice-daily applications to the feet will be monitored. METHODS: The study was randomized, bilateral, controlled and evaluator-blind. The first part of the study included 12 healthy volunteers and the second part 50 patients with hyperkeratotic feet. The changes in the skin was evaluated by an expert, the patients and using non-invasive biophysical measurements of skin barrier function (transepidermal water loss, TEWL), erythema, thickness (ultrasound) and hydration (conductance). RESULTS: The humectant-rich formulation increased skin hydration, removed scales and reduced thickness of hyperkeratotic skin. Skin barrier function was improved in normal skin, but no changes in TEWL were noted in the feet. No difference between once and twice-daily applications was found. Some smarting and stinging was noted. CONCLUSION: The humectant-rich formulation efficiently relieved the xerosis on the feet without inducing any weakening of the skin barrier function. Instead the normal skin became more resistant to external insults by the treatment.

Effect of moisturizers on epidermal barrier function.

A daily moisturizing routine is a vital part of the management of patients with atopic dermatitis and other dry skin conditions. The composition of the moisturizer determines whether the treatment strengthens or deteriorates the skin barrier function, which may have consequences for the outcome of the dermatitis. One might expect that a patient's impaired skin barrier function should improve in association with a reduction in the clinical signs of dryness. Despite visible relief of the dryness symptoms, however, the abnormal transepidermal water loss has been reported to remain high, or even to increase under certain regimens, whereas other moisturizers improve skin barrier function. Differing outcomes have also been reported in healthy skin: some moisturizers produce deterioration in skin barrier function and others improve the skin. Possible targets for barrier-influencing moisturizing creams include the intercellular lipid bilayers, where the fraction of lipids forming a fluid phase might be changed due to compositional or organizational changes. Other targets are the projected size of the corneocytes or the thickness of the stratum corneum. Moisturizers with barrier-improving properties may delay relapse of dermatitis in patients with atopic dermatitis. In a worst-case scenario, treatment with moisturizing creams could increase the risks of dermatitis and asthma.

No skin reactions to mineral powders in nickel-sensitive subjects.

BACKGROUND: Cosmetic products are known to be able to induce contact dermatitis. Contact dermatitis may also be induced by nickel, and it is estimated that up to 17% of women are allergic to nickel. OBJECTIVES: The aim of the present study was to investigate whether nickel sensitized individuals react to make-up products containing pigments with nickel as an impurity. PATIENTS/MATERIALS/METHODS: Twenty-three individuals with a clinical history of nickel allergy and/or with positive patch test reactions to nickel were exposed to mineral make-up products and individual pigments dispersed in alkylbenzoate (50%) in small Finn Chambers® for 48 hr. The skin reactions were evaluated visually and with a non-invasive instrument that quantifies skin erythema. RESULTS: The results showed that 74% of the included individuals showed a visible reaction to the positive control nickel sulfate, and a significant correlation was found between the visual and instrumental readings. However, none of the nickel sensitive individuals reacted to the test products. A subgroup analysis of the 50% most sensitive individuals also confirmed the absence of skin reactions to the powders. CONCLUSIONS: The bioavailability of the trace amounts of nickel in the particles was below the level needed to elicit an eczematous reaction in any of the nickel-sensitized individuals.

Treatment with a barrier-strengthening moisturizer prevents relapse of hand-eczema. An open, randomized, prospective, parallel group study.

Hand eczema influences the quality of life. Management strategies include the use of moisturizers. In the present study the time to relapse of eczema during treatment with a barrier-strengthening moisturizer (5% urea) was compared with no treatment (no medical or non-medicated preparations) in 53 randomized patients with successfully treated hand eczema. The median time to relapse was 20 days in the moisturizer group compared with 2 days in the no treatment group (p = 0.04). Eczema relapsed in 90% of the patients within 26 weeks. No difference in severity was noted between the groups at relapse. Dermatology Life Quality Index (DLQI) increased significantly in both groups; from 4.7 to 7.1 in the moisturizer group and from 4.1 to 7.8 in the no treatment group (p < 0.01) at the time of relapse. Hence, the application of moisturizers seems to prolong the disease-free interval in patients with controlled hand eczema. Whether the data is applic-able to moisturizers without barrier-strengthening properties remains to be elucidated.

Moisturizers change the mRNA expression of enzymes synthesizing skin barrier lipids.

In a previous study, 7-week treatment of normal human skin with two test moisturizers, Complex cream and Hydrocarbon cream, was shown to affect mRNA expression of certain genes involved in keratinocyte differentiation. Moreover, the treatment altered transepidermal water loss (TEWL) in opposite directions. In the present study, the mRNA expression of genes important for formation of barrier lipids, i.e., cholesterol, free fatty acids and ceramides, was examined. Treatment with Hydrocarbon cream, which increased TEWL, also elevated the gene expression of GBA, SPTLC2, SMPD1, ALOX12B, ALOXE3, and HMGCS1. In addition, the expression of PPARG was decreased. On the other hand, Complex cream, which decreased TEWL, induced only the expression of PPARG, although not confirmed at the protein level. Furthermore, in the untreated skin, a correlation between the mRNA expression of PPARG and ACACB, and TEWL was found, suggesting that these genes are important for the skin barrier homeostasis. The observed changes further demonstrate that long-term treatment with certain moisturizers may induce dysfunctional skin barrier, and as a consequence several signaling pathways are altered.

Long-term treatment with moisturizers affects the mRNA levels of genes involved in keratinocyte differentiation and desquamation.

In a recent study, we showed that long-term treatment with two different moisturizers affected TEWL in opposite directions. Therefore, we decided to examine the effect of these moisturizers on the cellular and molecular level. In a randomized controlled study on 20 volunteers, epidermal mRNA expression of genes essential for keratinocyte differentiation and desquamation after a 7-week treatment with two moisturizers was analyzed. Treatment with one test moisturizer increased gene expression of involucrin, transglutaminase 1, kallikrein 5, and kallikrein 7, while the other moisturizer affected only expression of cyclin-dependent kinase inhibitor 1A. Thus, moisturizers are able to modify the skin barrier function and change the mRNA expression of certain epidermal genes. Since the type of influence depends on the composition of the moisturizer, these should be tailored in accordance with the requirement of the barrier of each individual patient, which merits further investigations.

Changes in European legislation make it timely to introduce a transparent market surveillance system for cosmetics.

Marketing of cosmetics often makes strong claims linked to active ingredients. This is especially so for anti-ageing products, where the presentation and content of "active" ingredients may create new difficulties in their classification as cosmetics or medicinal products. A recent change in European legislation classifies a product as medicinal by virtue of its "function", in addition to the previous definition of "presentation" (i.e. marketing linked to diseases). Thus, formulations that also restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action should henceforth be covered by the Medicinal Products Directive. A cosmetic product must be suitable for its purpose and should not lead to adverse reactions that are disproportional in relation to its intended effect. However, the forthcoming ban on animal testing of cosmetic ingredients and the new European regulation, REACH (Registration, Evaluation and Authorisation of Chemicals), which aims to ensure a high level of chemical safety to protect human health and the environment, will probably have limited impact on the safety assessment of cosmetics. In order to enable consumers to make informed purchasing decisions, greater transparency in the process of assessing the performance of cosmetics is needed. Introduction of a more transparent system, enabling consumers and professionals to examine the scientific evidence for the claimed effect and the safety assessment of cosmetics, is therefore timely. Lack of transparency increases the risk of consumers wasting money on cosmetics that do not deliver the desired effects. This may jeopardize public trust in the cosmetic industry.

Facial anti-wrinkle cream: influence of product presentation on effectiveness: a randomized and controlled study.

BACKGROUND/AIMS: The great interest in eternal youth has developed a large market for skin care products claiming anti-wrinkle effects. A high-priced luxurious anti-wrinkle cream dispensed in its original packaging and in a neutral jar, were compared with the effects from a regular moisturizing face cream in a luxurious jar. METHODS: Eighty Swedish women aged 35-64 years were randomly divided into three groups; group A treated their facial skin for 6 weeks with the expensive cream in its luxury jar, B used a regular moisturiser filled in the luxury jar, and C used the expensive cream filled in a neutral jar. Evaluation was made by the subjects, clinical evaluation by a trained observer, and measurement of skin surface relief by optical profilometry. RESULTS: Participants using jars A and B consumed more product than participants using jar C, and the luxury jar thus resulted in better compliance. There were no significant differences between the three groups relating to the effects on wrinkles and smoothness, nor in subject assessment of their skin feeling younger or more beautiful. Facial appearance was the same. Profilometry showed reduced surface microrelief with all products. CONCLUSIONS: The present study conducted as a formal trial could not verify a claim of anti-wrinkle effect of a known prestigious product. Surprisingly, there was no systematic effect on subjective and objective cosmetic parameters of the luxury packaging, except a better compliance. Product appreciation by consumers may, however, be different in spontaneous use not biased by study conditions.

Effects of pretreatment with a urea-containing emollient on nickel allergic skin reactions.

The aim of this study was to evaluate the effect of a moisturizer containing urea on allergic contact dermatitis. Twenty-five nickel-sensitized patients and five controls (non-sensitized volunteers) applied such a moisturizer on the volar side of one forearm twice daily for 20 days, while the other forearm served as the control. After treatment with the moisturizer, patch tests with 0%, 0.5% and 2% NiSO4 in petrolatum were applied in a randomized manner on each arm. After 72 h, the skin reactions were blindly evaluated by clinical scoring and by measuring transepidermal water loss and electrical impedance. After treatment, the baseline transepidermal water loss values were lower and the baseline magnitude impedance index values were higher on the pretreated forearm. According to clinical scoring and measurements with the two physical measurement techniques, the degree of the patch test reactions was equal. All control subjects had negative nickel tests. We concluded that the skin reactivity to nickel in nickel-sensitized patients is not significantly affected by use of the urea-containing moisturizer.

Novel method for studying photolability of topical formulations: a case study of titanium dioxide stabilization of ketoprofen.

Sunlight may decompose active substances and excipients in pharmaceuticals. This may cause formulation problems as well as induce adverse skin reactions. The photodecomposition of topical preparations may occur on the skin surface, but also deeper in the skin after penetration of light into the viable tissues. The aim of the present study was to investigate whether microparticles of titanium dioxide could protect against photodecomposition using ketoprofen as a photolabile model substance. The results showed quality differences between titanium dioxide, where surface-coated particles were superior to pharmaceutical grades in reducing the degradation in vitro. The protective effect was also studied in humans. The skin was treated for 3 h with the gels and then exposed to ultraviolet (UV) light (11.7 J/cm2 UVA and 5.4 mJ/cm2 UVB). Layers of the stratum corneum were then removed by consecutive tape strippings and assayed for content of ketoprofen. The remaining amount was higher in the different stratum corneum compartments after treatment with a gel containing 4% coated titanium dioxide compared with a transparent gel. Thus, surface-coated microparticles of titanium dioxide may well be of clinical benefit in protecting photolabile drug substances against sunlight.

Treatment of surfactant-damaged skin in humans with creams of different pH values.

Skin surface has an acidic pH, whereas the body's internal environment maintains a near-neutral pH. The physiological role of the 'acidic mantle' and the function of the pH gradient throughout the stratum corneum remain unexplained. The pH gradient has been suggested to activate enzymes responsible for the maintenance of the skin barrier function and to facilitate the desquamation process in the stratum corneum. The aim of the study was to investigate the influence of pH of a moisturizing cream on barrier recovery in surfactant-damaged human skin. Volunteers had their skin damaged with sodium lauryl sulphate and treated those areas with the cream, adjusted to either pH 4.0 or 7.5. The study did not prove the superiority of a cream of pH 4.0 to a cream of pH 7.5 regarding promotion of skin barrier recovery, since no significant differences (p > 0.05) were found in transepidermal water loss, blood flow and skin capacitance between the treated areas.

Bioequivalence determination of topical ketoprofen using a dermatopharmacokinetic approach and excised skin penetration.

Ketoprofen is a photolabile drug. The aim of the present study was to compare the bioavailability of ketoprofen in a photo-stabilised formulation with a gel without photoprotection using a new dermatopharmacokinetic tape-stripping model and an established ex vivo penetration method using human skin. Analyses of the stratum corneum showed that during the first 45 min about 12 microg/cm2 ketoprofen was absorbed into the skin from the formulations. The area under the ketoprofen content-time curve (AUC0-6 h) for the ratio photo-stabilised gel/transparent gel was 73% with a 90% confidence interval (CI) 65-83. The rate of penetration of ketoprofen through isolated skin was approximately 0.2 microg/cm2 h for both formulations. AUC0-36 h for the ratio was 84% with 90% CI 64-105. Thus, the two methods did not disagree in terms of relative efficacy of the two gels. However, the difference obtained in vivo was statistically significant, whereas no significant data arise from the ex vivo study. Comparing the amount of ketoprofen in the skin after 45 min with the amount penetrated through the excised skin during 36 h, suggests a change in the thermodynamic activity of ketoprofen during the exposure. A supersaturated formulation may well have been formed initially due to evaporation of ethanol.

The irritation potential and reservoir effect of mild soaps.

Identification and reduction of external noxious factors is one key point in the strategy for the treatment and reduction of contact dermatitis. A wide variety of soaps on the market are claimed to be suitable for the use on sensitive skin due to their mildness. The aim of the present study was to illustrate possible differences in the irritation potential of 8 products and to investigate whether surfactant residues may form an irritant reservoir on the skin. The study was double-blind, randomized using healthy human volunteers. The inherent capacity of the products to induce irritation was determined using conventional patch test technique, whereas detection of potential surfactant residues on the skin was done using a methodology developed in the 1960s for detection of the corticosteroid reservoir in the stratum corneum. The method comprised the release of active substance from the stratum corneum reservoir by occlusion of the skin with an aluminium chamber, followed by evaluation of the biological response. In the present study, the soap-treated area was rinsed with water and then occluded. Instrumental measurements of the transepidermal water loss and superficial skin blood flow served as indicators of the injurious effects of the products. The results showed large differences in irritation potential between the products, and some of them demonstrated considerable damaging effect. Moreover, the study proved the presence of barrier-impairing residues on the skin after rinsing with water. Subclinical skin damage can make the skin vulnerable to further irritation and delay recovery of chronic irritant contact dermatitis.

Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders.

Emollients and moisturizing creams are used to break the dry skin cycle and to maintain the smoothness of the skin. The term 'moisturizer' is often used synonymously with emollient, but moisturizers often contain humectants in order to hydrate the stratum corneum. Dryness is frequently linked to an impaired barrier function observed, for example, in atopic skin, psoriasis, ichthyosis, and contact dermatitis. Dryness and skin barrier disorders are not a single entity, but are characterized by differences in chemistry and morphology in the epidermis. Large differences also exist between moisturizing creams. Moisturizers have multiple functions apart from moistening the skin. Similar to other actives, the efficacy is likely to depend on the dosage, where compliance is a great challenge faced in the management of skin diseases. Strong odor from ingredients and greasy compositions may be disagreeable to the patients. Furthermore, low pH and sensory reactions, from lactic acid and urea for example, may reduce patient acceptance. Once applied to the skin, the ingredients can stay on the surface, be absorbed into the skin, be metabolized, or disappear from the surface by evaporation, sloughing off, or by contact with other materials. In addition to substances considered as actives, e.g. fats and humectants, moisturizers contain substances conventionally considered as excipients (e.g. emulsifiers, antioxidants, preservatives). Recent findings indicate that actives and excipients may have more pronounced effects in the skin than previously considered. Some formulations may deteriorate the skin condition, whereas others improve the clinical appearance and skin barrier function. For example, emulsifiers may weaken the barrier. On the other hand, petrolatum has an immediate barrier-repairing effect in delipidized stratum corneum. Moreover, one ceramide-dominant lipid mixture improved atopic dermatitis and decreased transepidermal water loss (TEWL) in an open-label study in children. In double-blind studies moisturizers with urea have been shown to reduce TEWL in atopic and ichthyotic patients. Urea also makes normal and atopic skin less susceptible against irritation to sodium laurilsulfate. Treatments improving the barrier function may reduce the likelihood of further aggravation of the disease. In order to have optimum effect it is conceivable that moisturizers should be tailored with respect to the epidermal abnormality. New biochemical approaches and non-invasive instruments will increase our understanding of skin barrier disorders and facilitate optimum treatments. The chemistry and function of dry skin and moisturizers is a challenging subject for the practicing dermatologist, as well as for the chemist developing these agents in the pharmaceutical/cosmetic industry.

Differences among moisturizers in affecting skin susceptibility to hexyl nicotinate, measured as time to increase skin blood flow.

BACKGROUND/AIMS: A wide range of branded and generic moisturizers is frequently used for the prevention and treatment of dry skin. The influence of moisturizers on the skin permeability is pertinent to the understanding of their therapeutic efficacy. The aim of the present study was to compare the effect of two moisturizers on the skin permeability barrier, assessed as skin reactivity to a vasodilating substance. METHODS: The study was parallel, randomized and double blind on 53 healthy volunteers. One of the creams contained 5% urea, whereas the other contained no humectant but had a high lipid content. The participants were instructed to apply the cream twice daily for three weeks on the volar aspect of one of their forearms. The skin was then exposed to hexyl nicotinate, which induces vasodilation. The time-course and magnitude of the microvascular changes in the two skin areas were monitored with a non-invasive optical technique (laser Doppler flowmetry) with two measuring probes. RESULTS: The lag-time between application and initial response was significantly longer for the urea-treated site compared with the other cream. Furthermore, the time for maximum response was shorter for the lipid-rich cream than for its placebo. CONCLUSION: The study shows differences in action between moisturizers, which may influence the skin susceptibility to other irritants and allergens in the environment.