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Moisturizers in the Prevention and Treatment of Hand Eczema
Abstract
Hand eczema is common and multifactorial. A wide range of approaches is available for the management of the condition, in which moisturizing creams or emollients are important treatment adjuncts, both in the acute phase and to prevent outbreaks of eczema. However, moisturizers contain a great variety of ingredients that have different effects on the skin, some of which may be deleterious. The products can be regulated as pharmaceuticals, medical devices, and cosmetics.
The first-generation moisturizers were occlusive emollients based on petrolatum to reduce transepidermal water loss (TEWL) and to allow the epidermis to heal itself. The second-generation moisturizers contained humectants to bind water and lipids for temporary barrier improvement. Today’s “regular” moisturizers offer occlusive and humectant activity. The future products have occlusive and humectant properties and will contain ingredients for stimulating barrier repair based upon different dry syndromes. Products that not only diminish dryness symptoms but also repair the skin barrier and prevent barrier disruption would be the most valuable moisturizers. Thus, more evidence on their effectiveness compared to no treatment and compared to a reference or placebo is needed.
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The majority of moisturizing creams on the market are regulated as cosmetics. However, moisturizing creams may also be classified as pharmaceuticals (equivalent to medicinal products) or as medical devices within the European Member States. During recent years, there has been an increase in topically applied semi-solid formulations certified as medical devices.
The regulatory demands and the approval process differ between the three regulatory categories. The present chapter gives a brief overview of the differences and similarities between the categories, where the topics such as efficacy, safety, labeling, manufacturing, vigilance, post-marketing surveillance, qualified and responsible persons are addressed.
Specialized lipids found in the stratum corneum, namely ceramides, have been shown to have beneficial skin properties due to their lipid bilayer-forming potential in the presence of cholesterol and fatty acids. We were interested in determining whether other bilayer-forming lipids, such as phospholipids, could deliver similar benefits and how these benefits compare with common moisturizer ingredients such as petrolatum and glycerol. We investigated a bilayer-forming mixture of phospholipids, cholesterol, and fatty acid for its effectiveness in treating soap-induced winter xerosis in double-blind, fully randomized clinical trials in which dryness on the dorsal aspect of the hands was visually assessed using a seven-point grading scale. Sixty-six healthy Caucasian women aged over 25 underwent a one-week soap "dry-down" and were treated for two weeks with twice-daily product applications in balanced treatment groups (N = 11). Treatments were compared statistically using repeated Wilcoxon rank sum tests (critical significance level of 5%). Examination of improvements in xerosis in vivo established that emulsions of phospholipids, cholesterol, and stearic acid alone, or thickened solutions of glycerol alone, did little to alleviate skin xerosis. When lipids and glycerol were combined, however, the emulsions acted in a synergistic way and reduced skin xerosis significantly and rapidly. In contrast, when phospholipids were replaced with petrolatum in the emulsions, the rate of xerosis alleviation was reduced, which implies that the bilayer-forming capabilities of phospho- lipids may be important in delivering optimal skin benefit. These studies demonstrate that lipids with bilayer-forming capabilities such as phospholipids can rapidly alleviate skin xerosis when combined with glycerol.
Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.
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 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.
Dexpanthenol desires widespread use in medical and cosmetic applications for its wound-healing and cell growth stimulating activity. Nevertheless reports about contact dermatitis from dexpanthenol are rare in the literature. We report seven cases of contact dermatitis, in which dexpanthenol was the causative agent and induced clinically relevant sensitizations. We also discuss other cases described in the literature. Contact sensitization to dexpanthenol is not frequent but mostly of clinical importance in encountered cases. We therefore propose to include dexpanthenol in the patch test series of externally applied medicaments.
Most cosmetic products contain water, and water is essential for microbial growth. The availability of nutrients will enhance the growth of microbes, and most cosmetic products contain ingredients that can act as a nutrient source. Emulsion-based products, such as moisturisers, tend to contain higher levels of nutrient sources than most other product types and, as a consequence, tend to require most robust protection from microbial growth. This chapter will discuss the reasons why antimicrobial preservation is required; the possible effects of no, or inadequate, preservation; and highlight the most commonly used preservatives available to solve the problem. There will also be a discussion on preservative blends, so-called ‘secondary preservatives’ and the position on ‘preservative free’ claims. Finally, both human and environmental safety are considered.
Given that the preservation of moisturisers has many similarities with the preservation of most other cosmetic products, most of the information given here is of a general nature and equally applicable to all cosmetics that require preservation.
Maleic Acid is a dicarboxylic acid that functions as a fragrance ingredient and pH adjuster in cosmetics - it is used in a few cosmetic product formulations at low concentrations. Maleic Acid is commonly used in research studies to induce Fanconi syndrome in rats and dogs in an attempt to study the mechanism of this disease. One such study found decreased glomerular filtration rate in rats given 9.0 mmol/kg, but not with 1.5 mmol/kg, Maleic Acid intraperitoneally. Preincubation with 0.75 mmol/L of Maleic Acid reduced sperm penetration of golden hamster eggs to zero. Maleic Acid failed to induce any significant increases in revertant count in strains TA1535, TA1537, TA98, and TA100 at concentrations up to 7500 μg/plate. A concentration of 2.0 × 10-2 M Maleic Acid did show a positive pattern in a DNA synthesis inhibition test. Maleic Acid at 10%, pH 1.0, applied for 30 s on rabbit eyes, caused permanent opacity. A 1% solution, pH 1.0, applied for 2 min caused cloudiness of the cornea, but no lasting injury, and a 5% solution, also at pH 1.0, had a similar but more intense effect, with recovery delayed 6 to 7 days. Application of 10 μ l Maleic Acid (pH not stated) to the volar forearm and labia majora of 21 female Caucasians produced an inflammatory response at 24 and 48 h, which varied from minimal erythema to marked erythema with marked vesiculation. Maleic Acid at 20% (pH not stated) applied to one forearm daily for a period of 6 weeks to 50 human subjects produced acute vesicular dermatitis in 17 subjects, who were dropped from the study. Only five of the remaining subjects accommodated to the treatment, the rest had varying degrees of inflammation or hyperirritable skin. Although Maleic Acid itself may be a dermal and/or ocular irritant, its use as a pH adjustor in cosmetic formulations dictates that most of the acid will be neutralized into various maleate salts. Therefore, the concentration of free Maleic Acid is expected to be low, and dermal or systemic toxicity is not expected to be a concern. The safety of Maleic Acid as a pH adjustor should not be based on the concentration of use, but on the amount of free Maleic Acid that remains after neutralizing the formulation. There is no reason to expect this ingredient to induce any toxicity when used for this purpose. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that Maleic Acid is safe for use in cosmetic formulations as a pH adjustor in the practices of use as described in this safety assessment.
Aim. To determine the proportion of children with atopic eczema who develop cutaneous reactions to emollient creams and ointments. Design. Audit of immediate cutaneous reactions to emollient creams and ointments. The percentage of episodes of exposure to aqueous cream associated with immediate cutaneous reactions was compared with the percentage of episodes of exposure to all other emollients associated with these reactions. Subjects and Setting. The notes of 100 children aged 1 to 16 with atopic eczema attending a paediatric dermatology clinic at the Sheffield Children's Hospital. Outcome Measure. A history of an immediate cutaneous reaction, defined as one or more of burning, stinging, itching and redness, developing within 20 minutes of applying an emollient to the child's skin was recorded. Results. 56% of the episodes of exposure to equeous cream were associated with an immediate cutaneous reaction. Of the 622 episodes of exposure to all other emollients, 111 (17.8%) were associated with an immediate cutaneous reaction. The difference was statistically significant (P<0.001). Conclusion. The key to successful emollient therapy is education and tailoring the treatment to the individual child. Cutaneous reactions are one consideration; others include cosmetic acceptability and quantity applied. In our hospital this service is provided by specialist nurses, pharmacists and dermatologists. Community pharmacists could make a major contribution in this area by actively encouraging effective emollient use.
Two studies were performed to evaluate the influence of glycerol on the recovery of damaged stratum corneum barrier function. Measurements of transepidermal water loss and capacitance were conducted in a 3-day follow-up after tape stripping (study 1) and a 7-day follow-up after a barrier damage due to a repeated washing with sodium lauryl sulphate. In study 1 a faster barrier repair (transepidermal water loss) was monitored in glycerol-treated sites. Significant differences between glycerol open vs. untreated and glycerol occluded vs. untreated were observed at day 3. Stratum corneum hydration showed significantly higher values in the sites treated with glycerol + occlusion, compared with all other sites. In study 2 a faster barrier repair was seen in glycerol-treated sites, with significant differences against untreated and base-treated sites 7 days after the end of the treatment. Stratum corneum hydration showed highest values in the glycerol treated sites after 3 days of treatment. Glycerol creates a stimulus for barrier repair and improves the stratum corneum hydration; stratum corneum hydration is not strictly related to barrier homeostasis and can be optimized by different mechanisms and pathways. The observed effects were based on the modulation of barrier repair and were not biased by the humectant effect of glycerol. As the glycerol-induced recovery of barrier function and stratum corneum hydration were observed even 7 days after the end of treatment, glycerol can be regarded as a barrier stabilizing and moisturizing compound.
The epidermis functions as a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes - the cornified layer, which forms the endpoint of epidermal differentiation and death. The cornified envelope replaces the plasma membrane of differentiating keratinocytes and consists of keratins that are enclosed within an insoluble amalgam of proteins, which are crosslinked by transglutaminases and surrounded by a lipid envelope. New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing our understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
• Fifty hospitalized dermatology patients participated in a study to evaluate the transfer of topically applied tetracycline hydrochloride-containing fluorescent ointments, creams, lotions, and tinctures from various sites of application. Patients were examined with a Wood's lamp 24 hours after application to determine the sites and areas of transfer. The topically applied medications did not remain confined to sites of initial application. The anatomic sites of initial application determined the pattern of transfer. Certain patterns of transfer were characteristic among groups of patients and for specific patients. The vehicle of the topical preparation greatly influenced the extent and sites of transfer.
(Arch Dermatol 1983;119:660-663)
Synopsis--Dry and flaky SKIN can result from a low extensibility in the STRATUM COR- NEUM. Because the EXTENSIBILITY of corneum depends upon its water content, HUMEC- TANTS are often added to skin products to increase the corneum water content. Measurements of extensibility and water holding capacity in isolated animal comeurn showed that conventional humectants such as glycerol, sorbitol or sodium lactate can be effective but that the effect is lost on rinsing the comeurn in water. It was found that isolated animal comeum adsorbed LACTIC ACID and that the resulting increase in extensibility was retained after rinsing in water. In consumer tests, hand skin dryness and flaking was assessed by trained observers. Two weeks' use of HAND LOTIONS, containing SODIUM LACTATE or lactic acid adjusted to pH 4, resulted in less hand skin dryness and flaking than the use of control lotions. A lactic acid lotion also resulted in less dryness and flaking than a sodium lactate lotion.
The management of atopic dermatitis includes moisturizing creams, although scientific studies of their influence on the skin are scarce. In the present randomized double-blind study, the effects of a new moisturizing cream were compared with those of an already registered medicinal cream in the treatment of dry, eczematous skin in atopic patients, using multiple methods. The new cream contained 5% urea as active substance and the established licensed cream contained 4% urea and 4% sodium chloride as active ingredients. The new cream was studied in 25 patients and the established cream was tested in 23 patients. The patients were asked to apply the cream to dry, eczematous areas at least once daily for 30 days. At inclusion in the study and after 15 and 30 days of treatment the severity of the dry skin was evaluated by a dermatologist, assessed by the patients and measured in terms of transepidermal water loss (TEWL) and skin capacitance. Both groups improved during the study, but no statistically significent differences between them were found. This multi-parametric approach covers different aspects of skin dryness and provides the possibility of evaluating treatment effects in a cost-effective way.
Hand eczema in relation to occupation was studied in an industrial city. Questionnaires were sent to 20,000 individuals aged 20–65 years, randomly selected from the population register of the city. Those subjects (1385) considering themselves to have had hand eczema within the previous 12 months were invited to a dermatological examination including patch testing. It was found that the reported 1-year period prevalence of hand eczema in the total sample was 11.8%. The only occupational group reporting a statistically significant higher 1-year period prevalence was service work, 15.4%. Among all occupations, cleaners turned out to have the highest period prevalence, 21.3%. Hand eczema was more common among people reporting some kind of occupational exposure. The most harmful exposure turned out to be to unspecified chemicals, water and detergents and dust and dry dirt. The use of protective gloves is reported and analyzed. The most common contact allergy was nickel, followed by cobalt, fragrance-mix, balsam of Peru and colophony A statistically significant increase in contact allergy to colophony for women in administrative work was found. It is concluded that the type of hand eczema that is mostly dependent on occupation is irritant contact dermatitis.
Background
In previous work we reported on the efficacy of cosmetic body lotions enriched with skin-identical lipids to reduce the transepidermal water loss (TEWL) of ageing and sodium lauryl sulphate (SLS)-damaged skin. The observations made depended on the experimental design and clearly raised the question of the importance of the galenic formulation of skin ceramide-containing products.Objectives
The aim of the present work was to study the different galenic forms in which ceramide 3B (0.2% w/v) can be incorporated into common o/w emulsions. In addition, we investigated whether supplementation of skin care products with ceramide 3B enriched with penetration enhancers and coemulsifiers could exert a beneficial effect on barrier function, done by measuring their effects on the TEWL of SLS-induced scaly skin.ResultsWe found that the technique of incorporating ceramide 3B into the o/w emulsions was important for their final stability. However, no additional positive effect on the TEWL values of SLS-damaged skin could be observed when the efficacy of the ceramide-containing emulsions was compared with that of proper controls.Conclusions
Although suitable galenic formulas were developed, no positive effect on TEWL could be observed when ceramide 3B was added in a final concentration of 0.2% (w/v) to different o/w emulsions and applied to SLS-damaged skin.
Alpha hydroxyacids (AHAs) are used to enhance stratum corneum desquamation and improve skin appearance. The purpose of this study was to evaluate whether some AHAs improve skin barrier function and prevent skin irritation. Eleven healthy subjects (aged 28 ± 6 years. mean ± SD) entered the study. Six test sites of 8×5 cm (four different AHAs, vehicle only (VE) and untreated control (UNT)) were selected and randomly rotated on the volar arm and forearm. The four different AHAs at 8% concentration in base cream were glycolic acid (GA), lactic acid, tartaric acid (TA) and gluconolactone (GLU). The products were applied twice a day for 4 weeks (2 mg/cm2). At week 4, a 5% sodium lauryl sulphate (SLS) challenge patch test was performed under occlusion for 6 h (HillTop chamber. 18 mm wide) on each site. Barrier function and skin irritation were evaluated by means of evaporimetry (Servomed EP-1) and chromametry (a* value, Minolta CR200) weekly, and at 0.24 and 48 h after SLS patch removal. No significant differences in transepidermal water loss (TEWL) and erythema were observed between the four AHAs at week 4. After SLS challenge. GLU and TA-treated sites resulted in significantly lower TEWL compared with VE, UNT (P<0.01) and GA (P<0.05) both at 24 and 48 h. Similarly, a* values were significantly reduced after irritation in GLU-and TA-treated sites. This study shows that AHAs can modulate stratum corneum barrier function and prevent skin irritation: the effect is not equal for all AHAs. being more marked for the molecules characterized by antioxidant properties.
Based on chemical, cellular, and molecular understanding of dermal sensitization, an exposure-based quantitative risk assessment (QRA) can be conducted to determine safe use levels of fragrance ingredients in different consumer product types. The key steps are: (1) determination of benchmarks (no expected sensitization induction level (NESIL)); (2) application of sensitization assessment factors (SAF); and (3) consumer exposure (CEL) calculation through product use. Using these parameters, an acceptable exposure level (AEL) can be calculated and compared with the CEL. The ratio of AEL to CEL must be favorable to support safe use of the potential skin sensitizer. This ratio must be calculated for the fragrance ingredient in each product type. Based on the Research Institute for Fragrance Materials, Inc. (RIFM) Expert Panel’s recommendation, RIFM and the International Fragrance Association (IFRA) have adopted the dermal sensitization QRA approach described in this review for fragrance ingredients identified as potential dermal sensitizers. This now forms the fragrance industry’s core strategy for primary prevention of dermal sensitization to these materials in consumer products. This methodology is used to determine global fragrance industry product management practices (IFRA Standards) for fragrance ingredients that are potential dermal sensitizers. This paper describes the principles of the recommended approach, provides detailed review of all the information used in the dermal sensitization QRA approach for fragrance ingredients and presents key conclusions for its use now and refinement in the future.
Water is a skin irritant which deserves attention because of its ubiquity. During the Vietnam war, soldiers suffered from painful swollen feet, so-called tropical immersion foot. In occupational dermatology, the importance of water as a skin irritant is especially appreciated. The irritancy of water has been demonstrated by occlusion experiments; occlusion with either closed chambers or water-soaked patches has been shown to produce clinical and histopathological inflammation. Functional damage, as revealed by increased transepidermal water loss, has also been shown. Repeated water exposure without occlusion caused an increase in blood flow on irritated skin; however, clinical evaluation did not show a difference in dryness or scaling. Several mechanisms such as osmolarity, pH, hardness and temperature might account for the irritancy of water. Extraction or dilution of natural moisturizing factors in the stratum corneum is another possible explanation. Occlusion per se also changes the physiology of skin and may trigger the activation of potentially active substances. However, much remains to be done to clarify the risk factors and mechanisms of water-induced irritation.
Hand eczema is a common and persistent disease with a relapsing course. Clinical data suggest that once daily treatment with corticosteroids is just as effective as twice daily treatment.
The aim of this study was to compare once and twice daily applications of a strong corticosteroid cream in addition to maintenance therapy with a moisturizer in patients with a recent relapse of hand eczema.
The study was a parallel, double-blind, randomized, clinical trial on 44 patients. Twice daily application of a strong corticosteroid cream (betamethasone valerate 0.1%) was compared with once daily application, where a urea-containing moisturizer was substituted for the corticosteroid cream in the morning. The investigator scored the presence of eczema and the patients judged the health-related quality of life (HRQoL) using the Dermatology Life Quality Index (DLQI), which measures how much the patient's skin problem has affected his/her life over the past week. The patients also judged the severity of their eczema daily on a visual analogue scale.
Both groups improved in terms of eczema and DLQI. However, the clinical scoring demonstrated that once daily application of corticosteroid was superior to twice daily application in diminishing eczema, especially in the group of patients with lower eczema scores at inclusion.
Twice daily use of corticosteroids was not superior to once daily use in treating eczema. On the contrary, the clinical assessment showed a larger benefit from once daily treatment compared with twice daily, especially in the group of patients with a moderate eczema at inclusion.
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Hand eczema is prevalent in the general population. It remains unclear whether or not filaggrin gene (FLG) null mutations increase the overall risk of hand eczema or only increase the risk of hand eczema in subjects with atopic dermatitis.
To investigate the association between FLG null mutations and hand eczema.
A random sample of 3335 adults from the general population in Denmark was patch tested, FLG genotyped for R501X and 2282del4 null mutations and questioned about hand eczema.
Participants with combined presence of atopic dermatitis and FLG null mutation status had a significantly higher prevalence of hand eczema, an earlier onset of hand eczema and a higher persistence of hand eczema compared with subjects with normal FLG status and absence of atopic dermatitis. Logistic regression analyses revealed positive associations between hand eczema within the past 12 months and FLG null mutation status in participants with a history of atopic dermatitis [odds ratio (OR) 2.98; 95% confidence interval (CI) 1.27-7.01], but not in subjects without atopic dermatitis (OR 0.82; 95% CI 0.41-1.67).
FLG null mutations were significantly associated with hand eczema (< 12 months) in subjects with atopic dermatitis. Combined atopic dermatitis and filaggrin null mutation status was strongly associated with early onset of hand eczema and hand eczema persistence.
Healthcare-associated infection is an important worldwide problem that could be reduced by better hand hygiene practice. However, irritant contact dermatitis of the hands as a result of repeated hand washing is a potential complication that may be preventable by the regular use of an emollient.
To assess the effect of moisturizer application after repeated hand washing (15 times daily) vs. soap alone.
In a double-blind, randomized study, the effect of five different moisturizers on skin barrier function was determined by assessment after repeated hand washing over a 2-week period in healthy adult volunteers. Assessments of transepidermal water loss (TEWL), epidermal hydration and a visual assessment using the Hand Eczema Severity Index (HECSI) were made at days 0, 7 and 14.
In total, 132 patients were enrolled into the study. A statistically significant worsening of the clinical condition of the skin as measured by HECSI was seen from baseline to day 14 (P = 0.003) in those subjects repeatedly washing their hands with soap without subsequent application of moisturizer. No change was seen in the groups using moisturizer. Subclinical assessment of epidermal hydration as a measure of skin barrier function showed significant increases from baseline to day 14 after the use of three of the five moisturizing products (P = 0.041, 0.001 and 0.009). Three of the five moisturizers tested led to a statistically significant decrease in TEWL at day 7 of repeated hand washing. This effect was sustained for one moisturizing product at day 14 of hand washing (P = 0.044).
These results support the view that the regular application of moisturizers to normal skin offers a protective effect against repeated exposure to irritants, with no evidence of a reduction in barrier efficiency allowing the easier permeation of irritant substances into the skin as has been suggested by other studies. Regular use of emollient in the healthcare environment may prevent the development of dermatitis.
We recently found a very low adherence to a generally recommended skin protection regimen in a sample of 1355 metalworkers.
The present study assessed the effectiveness of skin protection as presently recommended, especially the differential contribution of skin care and skin protection, to the prevention of occupational hand eczema. Methods Of 1355 metalworkers screened, 1020 male volunteers, all fit for work, were recruited for a prospective intervention study with four arms (skin care, skin protection, both combined, and control group, i.e. no recommendation). The study was performed from winter 2006/2007 to spring 2008, following each subject for up for 12 months. Both hands were examined using a quantitative skin score, and a standardized personal interview was performed three times. The change of the objective skin score from baseline to 12 months was used as primary outcome measure.
After 12 months 800 subjects were included (78.4% of those recruited). The compliance to follow the randomized measure depended on the recommended measure and ranged from 73.7% to 88.7%. While in the control group a significant deterioration was found, the largest and significant improvement was noted in the group following the generally recommended skin protection programme (skin care + skin protection) followed by skin protection alone as second best.
The generally recommended skin protection regimen seems to provide effective prevention of occupational skin disease. Therefore, the compliance to follow the skin protection regimen, especially the use of skin protection, should be enhanced.
Dexpanthenol-containing creams have been widely used for treatment of lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A catalyses early steps in the synthesis of fatty acids and sphingolipids which are of crucial importance for stratum corneum lipid bilayers and cell membrane integrity.
In the present study, the effects were examined of a dexpanthenol-containing cream on skin barrier repair, stratum corneum hydration, skin roughness, and inflammation after sodium lauryl sulphate (SLS)-induced irritation.
Irritation was induced by application of SLS in patch test chambers. The dexpanthenol-contaming cream or the vehicle were applied twice daily and barrier repair, hydration, roughness, and inflammation of the skin were determined by using biophysical methods.
Significantly accelerated skin barrier repair was found in treatments with the dexpanthenol-containing cream (verum) compared with vehicle-treated (placebo) or untreated skin. Both verum and placebo showed an increase in stratum corneum hydration, but significantly more so with the dexpanthenol-containing cream. Both creams reduced skin roughness, but again the verum was superior. The dexpanthenol-containing cream significantly reduced skin redness as a sign of inflammation in contrast to the vehicle, which produced no effect.
Treatment with a dexpanthenol-containing cream showed significantly enhanced skin barrier repair and stratum corneum hydration, while reducing skin roughness and inflammation.
The management of chronic hand eczema is often inadequate. There are currently no evidence-based guidelines specifically for the management of chronic hand eczema, and evidence for established treatments for hand eczema is not of sufficient quality to guide clinical practice. This consensus statement, based on a review of published data and clinical practice in both primary and secondary care, is intended to guide the management of chronic hand eczema. It describes the epidemiology and pathogenesis of hand eczema, its diagnosis and its effect on patients' quality of life. Management strategies include a skin education programme, lifestyle changes, and the use of emollients, barriers and soap substitutes. Topical drug therapy includes topical steroids and calcineurin inhibitors. Treatment with psoralen ultraviolet A and systemic therapies may then be appropriate, although there is no strong evidence of efficacy. Alitretinoin has been shown to be effective in a randomized controlled trial, and is currently the only treatment specifically licensed for the treatment of hand eczema. Recommendations for management are summarized in a treatment algorithm.
Genetic defects leading to skin barrier dysfunction were recognized as risk factors for atopic dermatitis (AD). It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens.
We investigated the effect of 2 common treatments, a calcineurin inhibitor and a corticosteroid, on the skin barrier.
In a randomized study 15 patients with AD were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks.
Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier, improved in both groups. Dye penetration, a marker of the outside-inside barrier, was also reduced in both drugs. Electron microscopic evaluation of barrier structure displayed prevalently ordered stratum corneum lipid layers and regular lamellar body extrusion in pimecrolimus-treated skin but inconsistent extracellular lipid bilayers and only partially filled lamellar bodies after betamethasone treatment. Both drugs normalized epidermal differentiation and reduced epidermal hyperproliferation. Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning.
The present study demonstrates that both betamethasone and pimecrolimus improve clinical and biophysical parameters and epidermal differentiation. Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD.
The role of bacterial infections in hand eczema (HE) remains to be assessed.
To determine the prevalence of Staphylococcus aureus in patients with HE compared with controls, and to relate presence of S. aureus, subtypes and toxin production to severity of HE.
Bacterial swabs were taken at three different visits from the hand and nose in 50 patients with HE and 50 controls. Staphylococcus aureus was subtyped by spa typing and assigned to clonal complexes (CCs), and isolates were tested for exotoxin-producing S. aureus strains. The Hand Eczema Severity Index was used for severity assessment.
Staphylococcus aureus was found on the hands in 24 patients with HE and four controls (P < 0.001), and presence of S. aureus was found to be related to increased severity of the eczema (P < 0.001). Patients carried identical S. aureus types on the hands and in the nose in all cases, and between visits in 90% of cases. Ten different CC types were identified, no association with severity was found, and toxin-producing strains were not found more frequently in patients with HE than in controls.
Staphylococcus aureus was present on hands in almost half of all patients with HE, and was significantly related to severity of the disease. This association indicates that S. aureus could be an important cofactor for persistence of HE.
Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction.
The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function.
Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator.
Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period.
Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.
While glucocorticoids (GC) exert beneficial effects (anti-inflammatory), they also have adverse effects on the epidermis including decreased epidermal differentiation, decreased keratinocyte proliferation, and decreased cutaneous permeability barrier homeostasis. Thus, the purpose of this study was to develop strategies to prevent these GC toxicities using simultaneous topical treatments in clobetasol-treated mice. While a triple-lipid mixture of stratum corneum lipids (ceramide, free fatty acid and cholesterol) was previously shown to reverse the GC-induced abnormality in cutaneous barrier function [J Invest Dermatol, 120 (2003) 456], this lipid mixture did not prevent the GC-induced abnormalities in either keratinocyte proliferation or differentiation. As activators of PPARalpha, beta/delta, gamma and LXR, regulate keratinocyte proliferation and differentiation and improve permeability barrier homeostasis, we next assessed the effects of these activators during concurrent GC treatment. Co-application of either ciglitazone (PPARgamma activator), clofibrate (PPARalpha activator) or 22R (OH) cholesterol (LXR activator) with clobetasol prevented the decrease in involucrin, filaggrin and loricrin expression. By contrast, a PPARbeta/delta activator (GW501516) normalized only the expression of involucrin and filaggrin but not loricrin. Moreover, topical application of PPARalpha, beta/delta or LXR activators partially prevented the decrease in keratinocyte proliferation in GC-treated murine skin, as measured using PCNA, while no effect was seen after co-treatment with PPARgamma activators. Finally, PPARgamma and PPARbeta/delta activators but not PPARalpha and LXR activators improved permeability barrier homeostasis in GC-treated mice. Together, these studies demonstrate that PPAR and LXR activators can prevent several of the adverse effects of topical GC on the epidermis.
The aim of the trial was to investigate whether the publicized effects of skin protection creams can be replicated in a real occupational setting during activities that expose the skin.
A prospective, randomized, four-tailed controlled pilot trial was performed to compare the effect of skin protection and skin care alone or in combination with cleansing against a control group (only cleansing). Two branches were selected for the investigation: the building industry and the timber industry. A total of 1,006 workers from these two branches were recruited, and out of these 485 workers were examined longitudinally for at least three time points over 1 year (lost for follow-up: 430 workers, exclusion: 91 workers). At each time point, as a primary outcome measure, we assessed the condition of the skin at both hands in a blinded manner and the individual was assigned to one of the following categories: no eczema, mild, moderate and severe eczema. As a secondary outcome measure, the worker's transepidermal water loss (TEWL) was measured under standardized conditions at the back of both hands. In addition, the workers were asked to evaluate their skin condition during the study.
With regard to differences in the occurrence of eczemas, we found only in workers in building industry without application of skin protection or skin care creams a statistical significant increase in the incidence between the first and the second visit and a statistical significant decrease in the incidence between the second and third visit. When evaluating the secondary outcome-measurement changes in the TEWL values, an improvement was found for the group skin protection and skin care in combination and by skin care alone. Females in the timber industry started with better TEWL values than males, which may be due to better overall skin care. In this group we found an improvement for the group skin protection and skin care in combination and by skin protection alone. For skin protection alone, we noted a slight, but not significant improvement in all other groups. The subjective improvement of skin condition was reported from the participants who used skin protection and skin care in combination.
Taking all these secondary-outcome measurements together, the main result of this study was that skin protection creams alone have a small effect on the skin barrier in workers in the building and timber industries compared with skin care alone or in combination with skin protection.
Aqueous solutions of polysorbate 20 undergo autoxidation on storage, with the peroxide number increasing and subsequently decreasing again, the acidity increasing continuously, the pH and surface tension falling and tending to level off, and the cloud point dropping sharply until turbidity begins at room temperature. The changes are accelerated by light, elevation of temperature, and a copper sulfate catalyst. At the same time, hydrolysis occurs, liberating lauric acid. Analysis of the alterations in these properties leads to the conclusion that hydrolysis has the major influence near room temperature and that oxyethylene undergoes chain shortening at temperatures above 40 degrees. However, evidence of degradation is detectable even in previously unopened commercial samples of polysorbates 20, 40, and 60, warranting attention to the stability of and standards for these surfactants as compared with the solid alkyl ether type of nonionic surfactant.
Two randomized, double-blind comparison studies were conducted to evaluate the efforts of 2 emollient dry skin creams containing urea in the management of dry skin in atopic patients. Cream with 10% urea was shown to be effective in the management of dry skin and hand dermatitis. The cream with a pH of 6 caused less burning.
The purpose of this study was to investigate the ability of eight different moisturizers to prevent irritant dermatitis. Twelve healthy female students washed the outer aspect of their upper arms with a liquid detergent for one minute twice a day for one week. Seven skin creams and one skin oil were applied to 3 x 7 cm areas of the left upper arm just after each washing, while the right upper arm was left untreated. Transepidermal water loss (TEWL) (mean) increased from 7.1 to 9.3 g/m2/h (p less than 0.001) and laser-Doppler flowmetry (LDF) value (mean) decreased from 11.8 to 10.8 arbitrary units (N.S.) in the left upper arm, but there was no statistical difference between the eight moisturizers. During the second week of the study, the test subjects did not continue washing their arms. Eight areas (3 x 7 cm) of the right upper arm were treated with the moisturizers twice a day. The mean TEWL value decreased from 20.3 to 8.6 (p less than 0.0011) over 7 days, but there were no significant differences between the individual moisturizers. The laser-Doppler values showed the same trend as the TEWL values. In conclusion, regular use of emollients prevented irritant dermatitis from a detergent.
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.