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A Double-Blind Study Comparing the Effect of Glycerin and Urea on Dry, Eczematous Skin in Atopic Patients
Abstract
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.
... Glycerin has many other health benefits. It helps retain moisture in the skin [99], increases its hysteresis (creep phenomenon) and distensibility [100], and protects skin against irritants, inflammation, and microbes [99,101,102]. Glycerin can improve bowel movements and aid the passage of stool to relieve constipation and strengthen the gut, and it also improves hydration and cardiovascular functions [103,104]. ...
... Glycerin has many other health benefits. It helps retain moisture in the skin [99], increases its hysteresis (creep phenomenon) and distensibility [100], and protects skin against irritants, inflammation, and microbes [99,101,102]. Glycerin can improve bowel movements and aid the passage of stool to relieve constipation and strengthen the gut, and it also improves hydration and cardiovascular functions [103,104]. In sports, the ingestion of glycerin in combination with excess fluid can lead to increased plasma osmolality, reduced urine volume, and expanded plasma volume [70]. ...
Dietary supplements are products taken orally, and they contain an ingredient intended to augment the diet. Many studies demonstrate clear alterations in microbe abundances and the production of microbiota-derived metabolites, such as short-chain fatty acids, following dietary changes. This review comprehensively explores the possible interactions among gut microbiota, lemon extracts, glycerin, and their mixture products. Lemon extracts/components are associated with a vast array of health benefits, including anti-inflammation, antioxidant, anti-atherosclerotic, and anti-diabetic effects. They are also associated with increased memory and decreased depression. Glycerin can reduce serum free fatty acids and mimic caloric restriction; its metabolites can function as a broad-spectrum antimicrobial. Additionally, glycerin has a dehydrating effect on the central nervous system and can reduce focal cerebral edema and improve performance by expanding plasma volume. However, it may also have side effects, such as hyperglycemia. Therefore, combined consumption of lemon extracts and glycerin may, in part, mitigate each other’s side effects while exerting their benefits. There is growing evidence that both lemon components and glycerin are metabolized by the gut microbiota and may modulate the intestinal microbiome composition. Therefore, gut microbiome alterations are also explored as an important mechanism in the gut–brain axis regulating various effects of these dietary supplements and their application in various noncommunicable neurological disorders.
... Topical application of emollients is also important for the treatment of AD [12][13][14]. Cutaneous barrier function is important for maintaining cutaneous conditions and plays significant roles in defending the skin against external stimuli such as allergens [15][16][17]. When the barrier is perturbed, multiple reactions occurred in the skin, such as the induction of cytokine cascade [18] and protease activation [19]. ...
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus, an impaired cutaneous barrier function and a disrupted water holding capacity. Levels of ceramides, which are major components of intercellular lipids and are crucial for their functions, are decreased in the stratum corneum of patients with AD. Treatments to increase ceramide levels are effective for AD care. Synthetic pseudo-ceramide (cetyl PG hydroxyethyl palmitamide (SLE66)), which has a structure developed via molecular designs, and a eucalyptus leaf extract (ELE) enhance ceramide synthesis in the epidermis. The topical application of a skin moisturizer containing SLE66 and ELE improves the barrier functions and water holding capacity of AD skin accompanied by an improvement in skin symptoms. This is a multifaceted review that summarizes the efficacy of the topical application of a skin moisturizer containing SLE66 and ELE on atopic dermatitis.
... Urea, which can be used as excipient in topical formulations at lower concentrations in Europe but is only approved as such in one topical drug delivery system by the FDA, as well as glycerol are effective humectants. In a double-blind, vehicle controlled study, both showed significant effects in reduction of dryness and irritation in atopic patients (8). Alphahydroxy acids, such as lactic, citric, or gluconic acid (may also be use in form of gluconolactone) have shown activity against acne. ...
It is widely accepted that excipients play a crucial role in efficacy, safety and quality of medicinal products. For topical drug delivery, there are particular aspects to consider. Excipients are responsible for the perception of the product by the patient and directly impact on well-being and adherence to the therapy. They can have a direct impact on the efficacy, e.g. through moisturizing or antimicrobial effects. Indirectly, they can influence efficacy through chemical penetration enhancement. More than 500 excipients are approved for topical drug delivery by the FDA. Many of them are complex and show substantial variability in potentially critical material attributes, which may affect the quality of the resulting drug product. Therefore, appropriate characterization is essential for the development of robust products. EXCIPIENTS ABSTRACT The reasons for this are complex (5) but the patient-friendliness of the vehicle clearly plays are role. Although smart formulation can make a difference, excipients obviously play a major role in perception of vehicles. Direct and indirect contributions of excipients to the effi cacy of topical medicines will be discussed below. CLASSES AND NUMBERS OF EXCIPIENTS APPROVED FOR TOPICAL DRUGS According to the FDA's "Inactive Ingredients Database" (6), more than 500 excipients are currently approved for the topical route of administration. The different classes of excipients can be derived from the nature of topical formulations. Often, they are "semi-solid"; this means they are structured liquids based on a liquid solvent system that may be hydrophilic (water-based) or lipophilic (oil-based). The structure can be provided by polymeric thickeners (gel formers) or liquid crystalline structures resulting from combinations of consistency agents and emulsifi ers. At rest, the formulations show a dominance of elastic (solid like) behavior, under shear (e.g. pumping, spreading) the structure collapses and viscous (liquid-like) properties prevail. Often, they represent disperse systems where an inner phase is dispersed in an outer or continuous phase; a typical example of this is an oil-in-water emulsion. Emulsions need to be stabilized, which is typically achieved by emulsifi ers, amphiphilic surfactants which reduce the surface energy between the phases, often supported by kinetic stabilization through steric repulsion or viscosity enhancement. In drug delivery, historical terms like cream, ointment, lotion, gel are still used to describe such systems. Buhse et al. (7) provide a useful decision tree for nomenclature. Therefore, emulsifi ers, polymeric thickeners and consistency agents, which provide structure and physical stability, represent important classes of excipients. Emulsifi ers are the most extensive class with around 150 compounds (Figure 1). One reason for that is that depending on the composition of an emulsion and the phase behavior (oil-in-water or water-in-oil) a variety of hydrophilic-lipophilic balance (HLB) values are required. Historically, ionic surfactants were often used, which are now largely replaced by non-ionic surfactants. Very often, the hydrophilic part consists of polyoxyethylene (PEG) chains.
The term “risk assessment” is often substituted with “safety assessment”, to demonstrate the safe properties of cosmetic ingredients and formulations. With respect to the actual legislative framework, the proper use of in silico evaluation could offer a representative non-animal substitute for the toxicity evaluation of cosmetic ingredients. The in silico assessment needs to be integrated with other lines of proof (in vitro and/or in vivo data) in the form of a complex methodology in order to demonstrate the safety evaluation of cosmetic ingredients/products. The present study aimed to develop and characterize a new cosmetic formulation, designed for the skin care of the periorbital area. Quality control comprising stability, physicochemical, and microbiological evaluation was performed. Another objective of this study was to present a screening model for the safety evaluation of the cosmetic formulation by identifying individual ingredients, and to confirm the skin compatibility based on in vivo evaluation. The results demonstrated the in silico and in vivo safety profile of the cosmetic ingredients used in the present formulation. In silico evaluation, using a novel, specific software applicable for the risk evaluation of ingredients and formulations, showed that the incorporated ingredients were non-mutagenic and non-sensitizing, and considering the margin of safety (MoS), the cosmetic raw materials could be considered safe. Skin compatibility was confirmed by the patch test performed under dermatological control, evidencing the “non-irritating” potential of the developed cosmetic formulation.
Обоснование. Atopic dermatitis (AD) is one of the most common skin disorders in pediatric practice. In AD, the barrier function of the skin and moisturizing factors are impaired, which requires using specialized care products. Therefore, healthcare professionals should be aware of effective and safe products that can be used in children. Aim. To evaluate the clinical efficacy of LA-KRY cosmetics. Materials and methods. The study included 39 patients with AD and 26 patients with allergic/contact dermatitis aged 0-7 years. In some children, skin corneometric indices (SCI) (humidity and oiliness) were measured before using care products and 14 and 30 days after the start of their use to assess their effectiveness. In the remaining patients, the clinical manifestations of skin disorders were assessed visually without instrumental methods. Results. SCI improvement was observed after 14 days of using LA-KRY products and significantly improved by the end of month 1. Minimization of dryness and itching of the skin occurred by days 3-5, and clinical manifestations resolved by days 14-30 (depending on the nosology). Conclusion. LA-KRY have shown their effectiveness in children with several dermatoses associated with skin barrier disruption, dryness, and itching; in particular, they help reduce inflammation and discomfort and normalize SCI.
Atopic dermatitis (AD) is a common inflammatory skin condition found worldwide. It impacts patient quality of life (QoL) and is thought to arise as an inflammatory response to epidermal barrier dysfunction and hypersensitivity. AD can lead to large out-of-pocket costs and increased healthcare expenses over a lifetime. An analysis of all randomized control trials conducted since 1990 on topical therapies for AD were reviewed, including 207 trials in the final analysis. It was found that an average of 226 patients were enrolled over 2.43 arms. Common topical treatments included corticosteroids, calcineurin inhibitors, JAK inhibitors, and phosphodiesterase inhibitors. The most utilized tools to identify treatment efficacy were the EASI, IGA, SCORAD, and PGA. There was a paucity of data on trials that evaluated efficacy, QoL, and cost of treatment simultaneously. This review highlights the need for comprehensive trials that evaluate multiple aspects of treatment, including financial cost and QoL impact, to ensure each patient has the best treatment modality for the management of their AD.
Zusammenfassung
Diese S3‐Leitlinie wurde auf der Basis der europäischen S3‐Leitlinie unter besonderer Berücksichtigung der medizinischen Gegebenheiten im deutschsprachigen Raum und mit Ergänzungen der deutschsprachigen Vorgängerversion erstellt. Die interdisziplinäre Leitlinienkommission bestand aus Vertretern der Deutschen Dermatologischen Gesellschaft, dem Berufsverband der Deutschen Dermatologen, der Österreichischen Gesellschaft für Dermatologie und Venerologie, der Schweizerischen Gesellschaft für Dermatologie und Venerologie, der Deutschen Gesellschaft für Allergologie und Klinische Immunologie, der Deutschen Gesellschaft für Kinder‐ und Jugendmedizin, dem Berufsverband der Kinder‐ und Jugendärzte, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin, der Deutschen Gesellschaft für Pädiatrische Rehabilitation und Prävention, der Deutschen Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie, dem Deutschen Netzwerk Versorgungsforschung, dem Deutschen Neurodermitis Bund und dem Deutschen Allergie‐ und Asthmabund. Dieser erste Teil der Leitlinie geht auf die Definition und die diagnostischen Aspekte der atopischen Dermatitis (AD) ein, behandelt die topische Therapie sowie die nichtmedikamentösen Therapieverfahren wie die UV‐Therapie, die psychoedukative Therapie, diätische Interventionen bei AD, die Allergen‐spezifische Immuntherapie bei AD und die Komplementärmedizin. Auch behandelt dieser Teil der Leitlinie die besonderen Aspekte der AD bei Kindern und Jugendlichen, in der Schwangerschaft und in der Stillzeit sowie bei Kinderwunsch. Außerdem wird auf berufsbezogene Aspekte der AD eingegangen und die Perspektive der Patienten hervorgehoben. Der zweite, separat publizierte Teil der Leitlinie adressiert die systemische Therapie der AD.
This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German‐speaking region and incorporating additions from the previous German‐language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association.
This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non‐pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.
Atopic dermatitis is a prevalent chronic skin inflammation affecting 2.1 to 4.1% of adults globally. The complexity of its pathogenesis and the relapsing nature make it challenging to treat. Current treatments follow European Academy of Dermatology and Venerology guidelines, but advanced cases with recurring lesions lack effective therapies. To address this gap, researchers are exploring nanotechnology for targeted drug delivery. Nanoparticles offer benefits such as improved drug retention, stability, controlled release and targeted delivery through the disrupted epidermal barrier. This integrated review evaluates the current state of AD treatment and highlights the potential of novel nano-formulations as a promising approach to address the disease.
Background:
Moisturizers are first-line therapy for treatment of atopic dermatitis (AD). Although there are multiple types of moisturizers available, head-to-head trials between different moisturizers are limited.
Objective:
To evaluate if a paraffin-based moisturizer is as effective as ceramide-based moisturizer in children with AD.
Materials and methods:
In this double-blind, randomized comparative trial of pediatric patients with mild to moderate AD, subjects applied either a paraffin-based or ceramide-based moisturizer twice daily. Clinical disease activity using SCOring Atopic Dermatitis (SCORAD), quality of life using Children/Infants Dermatology Life Quality Index (CDLQI/IDLQI), and transepidermal water loss (TEWL) were measured at baseline and at follow-up at 1, 3, and 6 months.
Results:
Fifty-three patients were recruited (27 ceramide group and 26 paraffin group) with a mean age of 8.2 years and mean disease duration of 60 months. The mean change in SCORAD at 3 months in the ceramide-based and paraffin-based moisturizer groups was 22.1 and 21.4, respectively (p = .37). The change in CDLQI/IDLQI, TEWL over forearm and back, amount and days of topical corticosteroid required, median time to remission and disease-free days at 3 months were similar in both groups. As the 95% confidence interval (CI) of mean change in SCORAD at 3 months in both groups (0.78, 95% CI: -7.21 to 7.52) was not within the predefined margin of equivalence (-4 to +4), the conclusion of equivalence could not be proven.
Conclusion:
Both the paraffin-based and ceramide-based moisturizers were comparable in improving the disease activity in children with mild to moderate AD.
The combination of sodium chloride and urea in equal parts has shown a synergistic effect in regard to the water-retaining property of human skin. A cream with 4% sodium chloride and 4% urea, called 'salt cream' was tested in a double-blind investigation on asteatosis, with the symptoms dryness and scaling but without any inflammation, and showed a good clinical effect. There was a statistically higher significant difference (p<0.001) between the cream with sodium chloride and urea and the same cream but without these components. A second double-blind investigation was then made in order to evaluate the effect on inflammatory skin disorders - e.g., dry and scaly eczemas. Cortesal® (a cream with 4% sodium chloride, 4% urea and 0.5% hydrocortisone alcohol) was significantly better than a conventional hydrocortisone acetate cream 1%, on the symptoms dryness (p<0.01), erythema (p<0.05) and scaling (p<0.05) and equally good on itching and lichenification. The total effect, estimated by the doctor, was also in favour of Cortesal® (p<0.01).
A population of 1,077 persons (568 men; mean age 21 years old and 509 women; mean age 28.5 years old), students at a college of health and caring science and conscripts, were interviewed about their use and any side effects of cosmetics and toiletries during the last five years. Soap, toothpaste and deodorants were used daily by more than 80% of all the participants. Six per cent of the men and 18% of the women claimed adverse reactions from a total of 180 cosmetic products. Most commonly reported were eczematous reactions. Among the men the largest number of adverse effects was correlated to the use of deodorants. In women eye cosmetics were by far the most commonly claimed offending products. When persons reporting side effects were patch tested with a test panel containing several cosmetic allergens, 29% of them showed positive results, but only 11 of the 40 positive test reactions were evaluated as being relevant. In accordance with earlier reports, only a minor proportion of the subjects could thus be declared contact allergic and it is suggested that most of the cosmetic-related side effects were of the irritant type.
The management of atopic dermatitis includes moisturizing creams to reduce the dryness. The adverse skin reactions during topical treatment with two medicinal moisturizers were monitored in a double-blind randomized study on two parallel groups of patients with dry, eczematous skin. One cream contained 4% urea and 4% sodium chloride as active ingredients (23 patients), and the other 5% urea (25 patients). The patients were asked to apply the cream at least once daily for 30 days. The cream containing urea and salt induced skin sensations in about 60% of the patients. Significantly fewer patients experienced sensations with the 5% urea cream. Interestingly, no correlation was found between the severity of the dry skin condition and the degree of smarting. The degree of smarting did not change from day 15 to day 31. The face was reported by the patients to be most sensitive area and five patients (four in one group and one in the other) discontinued or reduced treatment of that area
Evaluation of dermatitis associated with propylene glycol application or ingestion remains a challenge. The research dealing with skin reactions to propylene glycol is revisited and new aspects for future research are outlined. Based on literature review and our own observations, we propose classifying skin reactions to propylene glycol into 4 mechanisms: (a) irritant contact dermatitis, (b) allergic contact dermatitis, (c) non-immunologic contact urticaria, and (d) subjective or sensory irritation. This concept allows a partial explanation of effects observed by different authors. Despite attempts to define objective criteria, biologically, histopathologically, or clinically, the distinction between irritant and allergic reactions remains unclear. Furthermore, the irritation threshold of propylene glycol, and likewise the optimal standard concentration in patch tests, is sub judice. Future studies on propylene glycol dermatitis should include repeated patch tests with serial dose dilutions, repeated open application tests/provocative use tests, oral challenge tests, and biopsies for a more complete evaluation of mechanisms and clinical significance.