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A Double-Blind Study Comparing the Effect of Glycerin and Urea on Dry, Eczematous Skin in Atopic Patients

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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.
... Other rarer adverse effects include irritant contact dermatitis, allergic contact dermatitis, occlusive folliculitis, photosensitive eruptions, acne cosmetica, and contact urticaria. Urea, lactic acid, glycerol, linoleic acid, and preservatives such as benzoic or sorbic acid have been reported to be associated with local irritation [6,[10][11][12]. Urea-containing creams, when used on AD patients, have been reported to produce stinging and burning sensations, itch, and even excoriations in some series, especially when used as a 10% preparation, with more acidic-based preparations or in combination with topical 1% hydrocortisone [11]. ...
... The choice of moisturizers should also be suited to the patient's needs and preferences and based upon the skin condition, tolerability, climatic condition, lifestyle, and affordability [8,14,15]. Our findings support and add to the existing literature on the irritation potential of a commercially available moisturizer compared with urea cream in the treatment of AD and will be useful in guiding physicians on recommendations for Fig. 1 Flow diagram of subject disposition moisturizers for their AD patients as well as to improve patient compliance [10][11][12]. The urea cream can still be beneficial for AD children with nonexcoriated chronically xerotic skin for maintenance therapy but should be avoided in acute flares, especially in the presence of excoriations. ...
Article
IntroductionMoisturizers are one of the mainstays of the topical treatment of atopic dermatitis (AD). One of the adverse effects of moisturizers is skin irritation, especially on excoriated AD skin. We compared the potential for irritation of two commercially available moisturizer products for the treatment of AD: a ceramide-based moisturizer (Ceradan® Cream; Hyphens Pharma Pte Ltd, Singapore) and a urea 5% moisturizer (Aqurea Lite Cream; ICA Pharma Pte Ltd, Singapore).Methods We performed a prospective single-blind randomized controlled study recruiting AD patients aged between 8 and 16 years with symmetrical or near symmetrical scratch marks (excoriations) of at least grade 2 to 3 severity score, according to the Eczema Area and Severity Index (EASI), over bilateral antecubital fossae. Subjects were randomized to receive the ceramide-based moisturizer to either the left or right antecubital fossa or urea 5% cream to the other antecubital fossa. Subjects were asked to grade the immediate skin irritation of both creams on a standard visual analogue scale (VAS) and which cream they would prefer to use as a daily moisturizer. Primary outcome was the mean irritant score of each cream, and secondary outcome was the subjects’ preference of either cream as their daily moisturizer.ResultsA total of 42 participants were enrolled with a mean age of 11 years 5 months. The ceramide-based cream had a significantly lower mean VAS score (mean 0.69, SD = 1.63) for irritation compared with urea 5% cream (1.43, SD = 1.64) (p = 0.035). More participants also preferred the ceramide-based cream over urea 5% cream (62% versus 38%) as their daily moisturizer, but this did not reach statistical significance (p = 0.164).ConclusionsA ceramide-based moisturizer may be considered as a suitable choice for children to minimize irritation from moisturizer treatment for AD.
... In a murine model of AD, a urea-based formulation improved the antimicrobial defense and the barrier function of the skin by regulating genes involved in the production of antimicrobial peptides, differentiation of keratinocytes and lipid synthesis [8]. The use of topical urea at concentrations ranging from 4% to 20% has been documented in multiple clinical trials [18][19][20][21][22][23][24][25]. A systematic review of the use of emollients in AD found that clinical effectiveness appears most well documented for ureabased preparations and recommends topical urea as a first-line choice in AD [18]. ...
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Urea is a hygroscopic molecule (capable of absorbing water) present in the epidermis as a component of the natural moisturizing factor (NMF) and is essential for the adequate hydration and integrity of the stratum corneum. Urea improves skin barrier function including antimicrobial defense by regulating gene expression in keratinocytes relevant for their differentiation and antimicrobial peptide production. It also plays a fundamental role in regulating keratinocyte proliferation. One of the first uses of urea in modern medicine was the topical treatment of wounds due to its proteolytic and antibacterial properties. At present, urea is widely used in dermatology to improve skin barrier function and as one of the most common moisturizers and keratolytic agents. Urea-containing formulations are available in diverse formulations and concentrations. Multiple clinical trials on the use of urea-containing formulations have shown significant clinical improvement in many of the dermatosis presenting with scaly and dry skin such as atopic dermatitis, ichthyosis, xerosis, seborrheic dermatitis and psoriasis, among others. Furthermore, urea can increase skin penetration and optimize the action of topical drugs. Urea-based products are well tolerated; their side effects are mild and are more frequent at high concentration. Here, we present a review of the use of urea in dermatology, discussing its mechanism of action, safety profile and frequent indications.
... It has been revealed that the use of topical moisturizers improves the moisture content of the stratum corneum, that reduced in atopic dermatitis, and restores and maintains the skin barrier function, leading to the prevention of allergen penetration, prevention of dermatitis flare-ups, and suppression of itching. 6,7 In the Japanese guidelines for atopic dermatitis 2020, the use of topical moisturizers all over the body including the sites that appear to be normal is highly recommended. 8 It is reported that mutations in filaggrin (FLG), a key structure of the epidermal differentiation complex which regulates homeostasis of the skin, causes various skin diseases such as ichthyosis vulgaris, AD or irritative contact dermatitis. ...
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It has been known that the use of moisturizers is useful in preventing the onset and maintaining remission of atopic dermatitis (AD). We recently focused on the moisturizing effect of natural mineral dissolved water and have conducted various studies. In this study, we investigated whether the bath treatment using natural mineral dissolved water can improve dry skin in AD patient in prospective nonblind, nonrandomized controlled study. Thirteen adults with almost clear to moderate AD took bath therapy using tap water for 13 days, followed by bath therapy using natural mineral dissolved water for 13 days. Changes in the severity scoring, patient‐oriented eczema measure, pruritus numerical rating scale, transepidermal water loss (TEWL) and hydration were evaluated at day1, 14 and 28. Tap water using bath treatment did not change the severity scoring and itch associated score, and it partially decrease TEWL when compared with baseline condition. Bath treatment using natural mineral dissolved water slightly decrease eczema area and severity index (EASI) score and significantly decrease TEWL with respect to baseline condition. Moreover, in relatively severe AD analysis, bath treatment with mineral dissolved water significantly decreased EASI and TEWL. Based on these results, bathing with natural mineral dissolved water may be effective in improving the dry skin of atopic dermatitis. Further studies are needed to evaluate its effects more clearly. In this study, we investigate the effect of natural mineral dissolved water in restoration of dry skin in mild – moderate AD with bathing. Bathing using natural mineral dissolved water decreased EASI and TEWL more than using tap water.
... In addition, glycerin can be used as a moisturizer (47) for dry skin and scars (48). (49). Studies showed the positive effects of glycerin on wound healing, indicating that it is a bacteriostatic agent at high concentrations that decrease microbial density in the wound (48). ...
Article
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: Chronic wound healing remains a complicated issue in the world's scientific health society. Alterations in the human body conditions such as biochemical, immunological, and physiological states may lead to non-healing wounds, making the treatment an insurmountably long and expensive procedure. Diabetes mellitus disposes the body to many complicated conditions while preventing diabetic wounds away from the normal wound-healing process. As topical administration is a favorable route of treating wounds, here, in this article, different topical materials and their roles are briefly reviewed.
... 61,62 La urea puede causar irritación y disfunción renal en los bebés y debe evitarse; los niños pequeños deben tratarse con concentraciones más bajas que los adultos y en algunos estudios se ha observado que el glicerol es mejor tolerado. 63,64 La recomendación es usar emolientes sin enjuague inmediatamente después del baño. 60 Solo se deben usar preparaciones emolientes desprovistas de alérgenos proteicos y haptenos, los cuales con frecuencia causan alergia de contacto (como la lanolina, el alcohol de cera de lana, o metilisotiazolinona, y el propilenglicol), especialmente en el grupo de edad más vulnerable, como los menores de dos años. ...
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The skin is the largest organ in the human body. Among other components, it contains epidermal cells, which are modified epithelial cells that rest on a basal membrane that separates them from the dermis. When the epidermis presents variations in its structural composition and the distribution of its elements, the result is the loss of large amounts of water, which perpetuates these variations and leads to permanent dehydration. Emollients are the first line of treatment for pathologies that affect the hydration of the skin, such as atopic dermatitis, which is one of the most important ones. This document entails the description of the epidermal barrier with its main components and functions, the characteristics of an altered skin barrier, and the mechanisms for its repair. Subsequently, this paper includes the definition of emollient, hydration mechanisms for the recovery of the barrier, types of emollients, the situations that must be taken into account when the use of emollients is prescribed, evidence with or without connection with their advantages, and the key points at the time of its formulation.
... Few randomized trials assessed the clinical efficacy of glycerol for AD, despite its use being widely supported by guidelines (40). Although matching with the results of a previous 3week study of 20% glycerol in adults with AD (41), the 48% reduction of SCORAD achieved by concentrated glycerol in our study is lower than most previous reports of 15-20% glycerol application, which showed an average 60% reduction of variable clinical scores of AD (42)(43)(44). This could be easily attributed to the drying effect of concentrated glycerol, an effect that we tried to palliate by petroleum jelly application to patients in both study arms. ...
Article
Background: Treating atopic dermatitis (AD) is still a challenge. The staphylococcal skin load is known to aggravate AD. Narrow band ultraviolet B (NB-UVB) and glycerol in low concentration (20-40%) are established therapies for AD. NB-UVB has proven antimicrobial actions, while high concentration glycerol (85-100%) showed similar effects in vitro but hasn’t been clinically tested. Objective: To evaluate the efficacy and tolerability of concentrated glycerol 85% compared to NB-UVB in patients with AD, as assessed by clinical improvement and reduction of staphylococcal colonization of the skin. Methods: 30 patients with mild to moderate AD were randomized into either nb-uvb or glycerol 85% group. Patients were treated for one month and followed for an additional month. Swabs were taken from the skin and nose to be cultured on mannitol-salt agar for Staphylococci and quantified to determine Colony Forming Units (CFU). Results: Both groups showed statistically insignificant microbial changes and statistically significant clinical improvement after treatment. The results were comparable between both groups. Conclusions: Concentrated glycerol 85% is a cheap effective readily accessible alternative for phototherapy in patients with mild-moderate AD who cannot access the facility. Reduction of staphylococcal skin load seems to be involved, but its role is minimal. Trial registration: Pan African Clinical Trial Registry (www.pactr.org) PACTR201810815694251
Chapter
Moisturizers help regulate the skin barrier and continue to be the foundation of maintenance treatment for atopic dermatitis. Though a tremendous variety of moisturizers at difference price points exist on the market, studies do not show that one moisturizer or moisturizer ingredient is significantly better than another in patients with atopic dermatitis.
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This is the English version of guidelines for the management of asteatosis 2021 in Japan. Asteatosis is a synonym of xerosis found in a wide range of diseases that induce dry skin through impaired functions of either water retention of the stratum corneum or skin covering with acid mantle. Patients with asteatosis may be accompanied by pruritus. Moisturizers are the first-line treatment for asteatosis and their adequate use must be recommended. The main purpose of the present guidelines is to define skin symptoms requiring treatment with moisturizers for medical use in patients with asteatosis. If the deterioration of marked scaling or scratch marks is predicted, therapeutic intervention with moisturizers for medical use should be considered even in the absence of pruritus. Regarding six important points requiring decision-making in clinical practice (clinical questions), we evaluated the balance between the benefits and harm of medical interventions in reference to previous reports of clinical research, and presented the recommendation grades and evidence levels to optimize the patient outcome by medical interventions.
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The goal of a treatment regimen for atopic dermatitis is to reach and maintain a state where the patient exhibits mild symptoms or an absence of symptoms, and the patient should not experience disturbance during daily activities. The basis of a treatment regimen for atopic dermatitis is topical therapy, and currently there exist topical corticosteroids, tacrolimus and delgocitinib. Using these, proactive therapy is performed as maintenance therapy after remission induction therapy. However, in cases of moderate to severe atopic dermatitis, topical drugs alone cannot induce remission and systemic therapies such as cyclosporin, ultraviolet therapy, and dupilumab should be used in combination. In particular, dupilumab has many advantages such as high efficacy, relatively few adverse reactions, and ease of use in elderly patients with severe atopic dermatitis. In this review, we present a treatment algorithm for atopic dermatitis that emphasizes the importance of maintaining remission after induction of remission, and summarizes the characteristics of current medication therapy for atopic dermatitis in Japan.
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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
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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.