A double-blind study comparing the effect of glycerin and urea on dry,eczematous skin in atopic patients

Moisturizing creams have beneficial effects in the treatment of dry, scaly skin, but they may induce adverse skin reactions. In a randomized double-blind study, 197 patients with atopic dermatitis were treated with one of the following: a new moisturizing cream with 20% glycerin, its cream base without glycerin as placebo, or a cream with 4% urea and 4% sodium chloride. The patients were asked to apply the cream at least once daily for 30 days. Adverse skin reactions and changes in skin dryness were assessed by the patient and a dermatologist. Adverse skin reactions such as smarting (a sharp local superficial sensation) were felt significantly less among patients using the 20% glycerin cream compared with the urea-saline cream, because 10% of the patients judged the smarting as severe or moderate when using glycerin cream, whereas 24% did so using urea-saline cream (p < 0.0006). No differences were found regarding skin reactions such as stinging, itching and dryness/irritation. The study showed equal effects on skin dryness as judged by the patients and the dermatologist. In conclusion, a glycerin containing cream appears to be a suitable alternative to urea/sodium chloride in the treatment of atopic dry skin.     

Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm)

Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.     

Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial

BACKGROUND: Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. OBJECTIVES: To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. METHODS: Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. RESULTS: Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. CONCLUSIONS: Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.     

Evaluation of out–in skin transparency using a colorimeter and food dye in patients with atopic dermatitis

Background  Atopic dermatitis is a disease of skin barrier dysfunction and outside stimuli can cross the skin barrier.
Objectives  To examine a new method for evaluating the outside to inside skin transparency with a colorimeter and yellow dyes.
Methods  In study 1, a total of 28 volunteer subjects (24 normal and four with atopic dermatitis) participated. After provocation with yellow dye, the skin colour of all the subjects was measured using a colorimeter. The skin transparency index was calculated by the changes of the skin colour to yellow. Other variables of skin function, including transepidermal water loss (TEWL) and stratum corneum hydration, were also measured. In study 2, the skin transparency index was evaluated for a cohort of 38 patients with atopic dermatitis, 27 subjects with dry skin and 29 healthy controls.
Results  In study 1, the measurement of skin colour (b*) using tartrazine showed good results. There was a significant relationship between the skin transparency index with tartrazine and the atopic dermatitis score ( P  =   0·014). No other measurements of skin function, including the TEWL, were correlated. In study 2, the skin transparency index score obtained with tartrazine in the patients with atopic dermatitis was significantly higher than that of the controls and those with dry skin ( P  <   0·001 and P  =   0·022, respectively). However, the TEWL in patients with atopic dermatitis was not significantly higher than that of patients with dry skin and the TEWL in subjects with dry skin was not higher than that of the controls.
Conclusions  This method, which used a colorimeter and food dye, is noninvasive, safe and reliable for the evaluation of out–in skin transparency and can demonstrate the characteristic dysfunction in the skin barrier in patients with atopic dermatitis.     

The influence of a single application of different moisturizers on the skin capacitance.

Moisturizers are believed to improve the skin condition by increasing the water content of the stratum corneum. A variety of techniques for assessing skin hydration has been developed. In the present study the capacitance following a single application of different moisturizers to normal skin on 12 volunteers was measured with the commercial available Corneometer 420. The moisturizers were pure petrolatum and three oil-in-water creams. The latter contained either glycerine, glycerine and pyrollidone carboxylic acid, or urea as humectant agents. The first measurement of the change in the capacitance was done 2 h after application of the products. All tested products increased the capacitance in the same order of magnitude. For the creams the values were significantly enhanced during the experimental period (6 h). Excess product were removed from some skin areas after the 2 h measurement. This caused immediately a significant decrease in the capacitance of the cream treated sites, whereas a tendency towards higher values were noted on the petrolatum-treated sites. These findings indicate that the non-absorbed components influences the capacitance values. Hence, the interpretation of electrical measurements with respect to skin moisture should be made with caution.     

Efficacy of bufexamac (NFN) cream in skin diseases. A double-blind multicentre trial.

The effect of a new non-steroid anti-inflammatory substance (bufexamac) in a special constituent was compared with that of 0.1% triamcinolone acetonide, 1% hydrocortisone cream, and placebo during a double-blind multicentre trial. The clinical effect of these four creams was studied in 193 patients receiving treatment for the following skin disorders: atopic dermatitis, allergic contact dermatitis, and non-allergic contact dermatitis, as well as dermatitis seborrheica. After 2 and 4 weeks' treatment, when 193 and 157 patients, respectively, were re-examined, the effect of triamcinolone acetonide and hydrocortisone cream was significantly better, than that obtained with bufexamac in the cream basis employed. On the other hand, no statistically significant difference in effect between bufexamac and placebo cream was observed.     

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.     

Simvastatin cream alleviates dermal fibrosis in a rabbit ear hypertrophic scar model

Background

Hypertrophic scars (HTS) result from injury to the skin and represent a clinical burden with limited treatment options. Previously, we demonstrated that statin drugs could attenuate HTS formation, but convenient topical delivery and retention of these drugs at the wound site remains a challenge.

Aims

Here, we aimed to develop a topical cream formulation that can deliver statin drugs simply and conveniently to reduce scar hypertrophy.

Methods

We formulated creams containing 10% pravastatin, 2% simvastatin, and 10% simvastatin. We tested these creams for their ability to reduce scar hypertrophy and attenuate dermal fibrosis in a clinically relevant HTS wound model performed in rabbit ear skin. We also monitored trans-epidermal water loss (TEWL) over the course of wound healing in order to understand the effects of statin treatment on epidermal barrier recovery.

Results

Of the three creams formulated, only application of 10% simvastatin cream significantly attenuated hypertrophy of resultant scars compared with vehicle cream application. Application of 10% simvastatin cream resulted in a decrease in macrophage and myofibroblast density at post-operative day 28 (POD28) harvest. Application of 10% simvastatin cream resulted in visible symptoms of dryness and increased TEWL at POD28, but subsequent withdrawal of statin cream treatment resulted in rapid alleviation of dryness and decrease in TEWL back to normal levels.

Conclusions

Our data demonstrate that topical administration of 10% simvastatin cream antagonizes dermal fibrosis and reduces hypertrophy in an HTS model, and withdrawal of the cream enables recovery of epidermal barrier and resolution of skin dryness.     

The effect of combined topical steroids and habit-reversal treatment in patients with atopic dermatitis

A modified behavioural method called habit-reversal, in combination with potent and weak corticosteroid cream, was compared with the use of the creams alone in the treatment of 45 patients with atopic dermatitis. The patients were randomly assigned to four groups, which received two different cream regimes in combination with the habit-reversal treatment. The patients' skin was assessed before, during and after treatment, and they recorded the amount of scratching during the study. The skin condition improved in all groups, but to a significantly greater degree in the habit-reversal groups. A strong correlation was found between the reduction in scratching and the improvement in skin status.     

Urea-containing moisturizers influence barrier properties of normal skin

Moisturizers are used in the treatment of dry skin, both clinically and in cosmetic products. In the present study the influence of different moisturizers on the normal skin barrier properties was evaluated by measuring transepidermal water loss (TEWL) and skin capacitance. In addition, the skin reactivity to a topically applied surfactant, sodium lauryl sulphate (SLS), following the use of the moisturizers was examined. The skin reaction was assessed visually and by measuring TEWL and superficial blood flow. Treatment with two urea-containing moisturizers for 10 and 20 days decreased TEWL. The irritant reactions after exposure to SLS were also significantly decreased after prior treatment for 20 days with the urea-containing moisturizers. In a double-blind vehicle-controlled part of the study, urea was found to decrease the skin susceptibility to SLS after only three applications. However, this decrease in skin reactivity was not preceded by a reduction in TEWL. Skin capacitance increased after three applications of urea-containing moisturizers and was still increased after 10 days, but not after 20 days of this treatment. Treatment for 20 days with two moisturizers without urea did not influence either TEWL or the susceptibility to irritation from SLS, but it increased the skin capacitance significantly. The mechanism underlying these changes is not known. The lower degree of SLS-induced irritation in the skin treated previously with urea-containing moisturizers may be of clinical relevance in reducing contact dermatitis from irritant stimuli. Received: 5 January 1995     

Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream

Moisturizers are used daily by many people to alleviate symptoms of clinically and subjectively dry skin. Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli. In the present single-blind study, a moisturizing cream was tested for its influence both on barrier recovery in surfuctant-damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate (SLS). Parameters measured were transepidermal water loss (TEWL) and skin corneometer values, indicating degree of hydration. Treatment of surfactant-damaged skin with the test cream for 14 days promoted barrier recovery, as observed as a decrease in TEWL. Skin corneometer values also normalized more rapidly during the treatment. In normal skin, use or the test cream significantly reduced TFWL after 14 days of treatment, and irritant reactions to SLS were, significantly decreased. Skin corneometer values increased after only 1 application and remained elevated after 14 days. In conclusion, the accelerated rate of recovery of surfactant-damaged skin and the lower degree of SLS-induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli.     

Susceptibility to irritants: role of barrier function, skin dryness and history of atopic dermatitis

The susceptibility of the skin to various irritants was investigated with the aim of determining the role of the barrier function of the stratum corneum, skin dryness and whether a history of atopic dermatitis (AD) was a factor. The transepidermal water loss (TEWL) was measured using an evaporimeter and skin hydration using a Corneometer and by visual scoring. The group with a history of AD (n = 20) had a lower pre-exposure barrier function and a higher TEWL value following irritant exposure than the group with a history of allergic contact dermatitis (n = 18) and a control group (n = 18). Clinically dry skin was more susceptible than normal skin, though no difference was noted in the pre-exposure barrier function. The increased susceptibility to irritants in those with a past history of AD was probably due to impaired barrier function and/or the presence of a dry skin.     

Do urea and sodium chloride together increase the efficacy of moisturisers for atopic dermatitis Skin? A comparative, double-blind and randomised study

Urea has long been used to treat dry skin. In the present report, we compared two creams, identical with the exception that one contained both urea and sodium chloride and the other urea alone, in 22 patients with atopic dermatitis. Following a 2-week wash-out period, their clinically non-eczematous, rough or normal-appearing skin on the forearms was treated twice daily in a double-blind and randomised manner. We examined the treated areas by measuring transepidermal water loss, capacitance and electrical impedance. Our findings suggest that a moisturiser containing both urea and sodium chloride seems somewhat more effective than the same moisturiser without sodium chloride, at least concerning the ability to reverse impedance indices of atopic skin towards normal, an effect ascribed mainly to changes in hydration of the stratum corneum. However, the clinical significance of our impedance measurements is somewhat premature to decide.     

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.     

Water, salts and skin barrier of normal skin

Background: We recently reported that open application of seawater for 20 min ameliorated experimental irritant contact dermatitis induced by sodium lauryl sulphate (SLS) cumulative irritation. The efficacy was overall contributed by 500 mm of sodium chloride (NaCI) and 10 mm of potassium chloride (KCl), which are consistent with the each concentration in seawater. Although the usefulness of mineral water with 500 mm NaCl and 10 mm KCl to treat atopic dermatitis (AD) or irritated skin was considered, seawater or its components would induce a feel of stinging in patients with AD. Furthermore, 20 min application was thought to be too long to use everyday as a treatment. Objective: We report the effects of 3 types of mineral water with NaCl and KCl to check the further efficacy with lesser stinging by 2 min application. Results: A mineral water with 250 mm NaCl and 50 mm KCl was the most effective water to prevent disruption of skin barrier and stratum corneum water content after cumulating irritation by SLS. Moreover, improvement of skin dryness and pruritus were shown 2 weeks after the application of the mineral water to a 6‐year‐old boy with atopic dermatitis. Conclusion: Our results suggested the possible usefulness of the mineral water with 250 mm NaCl and 50 mm KCl as the therapy of atopic dermatitis of other chronic dermatitis. Although the mineral water would not cure those skin diseases, it could be an adjunctive therapy. Further controlled clinical trials with evaluation by TEWL and capacitance are required to declare the efficacy of the mineral water in the treatment of patients with AD or other chronic dermatitis.     

Influence of creams with different urea concentrations on plantar skin hydration

IntroductionThe skin is the body's outermost organ, and one of its main functions is to provide protection against potential infections. Hydration is related to the proper functioning of the skin, hindering the appearance of wounds or cracks which could lead to the occurrence of infections or other dermatological alterations. The skin of the foot is thicker than that of the rest of the body due to the load it supports, and it is more complicated to maintain. The intention of this study was to evaluate the efficacy of different concentrations of urea (5% and 20%) in hydrating the foot compared to a placebo cream.MethodsThe study was carried out with 60 subjects of ages from 20 to 35 years in age. The experimental protocol was initiated by creating three randomized groups (1:1:1), each being treated with a different cream: placebo, 5% urea cream, and 20% urea cream. The examination was carried out using a non-invasive instrument (Corneometer CM 825®) that detects the skin surface hydration.ResultsAnalysis of the hydration of the different study zones according to the cream used showed no significant differences between the placebo and 5% urea for the first MTH and heel, but a significant difference for the fifth MTH. There were significant differences in all study areas between the placebo and 20% urea creams, but none between the 5% urea and 20%Discussion/ConclusionThe conclusion drawn was that skin hydration was greater with the 20% urea cream versus the placebo, but there were no differences found when comparing either the 20% and 5% urea creams or the placebo and 5% urea creams.     

Clinical and non-invasive evaluation of 12% ammonium lactate emulsion for the treatment of dry skin in atopic and non-atopic subjects.

Clinical dryness of the leg skin is a common problem among dermatological patients. The efficacy and safety of 12% ammonium lactate emulsion (Keratisdin) for the treatment of dry skin on the legs of atopic and non-atopic subjects has been assessed by clinical criteria and by five different non-invasive methods. These methods measure biophysical parameters such as electrical capacitance of stratum corneum, skin surface lipids, transepidermal water loss (TEWL), skin surface topography (scanning electron microscopy and image analysis) as well as the biomechanical properties of the skin. Treatment with the test emulsion significantly reduced the severity scores for dryness, desquamation and pruritus when measured 15 days later. All patients tested showed a significant increase in electrical capacitance, skin surface lipids, extensibility and firmness of the skin, and an improvement in the skin barrier function and skin surface topography. This study showed that non-invasive techniques are excellent complementary tools in clinical studies.     

Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis

To obtain data on the function of the epidermal barrier in patients with atopic dermatitis (AD) the transepidermal water loss (TEWL) was studied. Measurements were made on three body locations in two clinically well defined groups of patients with AD and in a control group. The TEWL was found to be increased both in dry non-eczematous skin and in clinically normal skin in patients with AD. The TEWL was highest in patients with dry skin. The result of the study may indicate a primary defect in the epidermal barrier: the stratum corneum.     

Correlation of clinical features and skin barrier function in adolescent and adult patients with atopic dermatitis

BACKGROUND: Xerotic changes in atopic skin are considered to be related to a decrease in the water permeability barrier. Whether abnormal skin barrier function is the main cause of atopic dermatitis (AD) or a secondary change of the disease is still controversial. Noninvasive bioengineering methods, including the measurement of the transepidermal water loss (TEWL) and water capacitance, have been commonly used to evaluate skin barrier function. AIM: To evaluate the correlation between the clinical features of each evaluation site (severity of AD) and skin barrier function. METHODS: TEWL, capacitance, and pH were checked on five evaluation sites: postauricle, forearm, abdomen, thigh, and popliteal fossa. The subjects included 25 patients, both adolescents and adults, with AD and 25 age-matched normal controls. The clinical severity, from 0 (no clinical manifestation) to 3 (severe), was also scored for erythema, induration/papulation, lichenification, and xerosis on each evaluation site of the AD patients. RESULTS: Based on the data, we found that the clinical severity score was correlated with TEWL and capacitance in more than one-half of the evaluation sites. Erythema and induration/papulation showed a statistically significant correlation with TEWL in most cases (P < 0.05, four sites). Lichenification and xerosis showed a significant correlation with capacitance in most cases (P < 0.05, four sites). In most cases, severity scoring of the clinical features did not show a significant correlation with skin pH. The patients showed higher TEWL and lower capacitance than normal controls (P < 0.05, all five sites). CONCLUSIONS: The results of our study suggest that skin barrier function, measured by TEWL and capacitance, and clinical severity show a statistically significant correlation in patients with AD.