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A New Approach to Atopic Dermatitis Control with Low-Concentration Propolis-Loaded Cold Cream.

ABSTRACT: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is difficult to treat. Traditional cold cream, a water-in-oil emulsion made from beeswax, is used to alleviate AD symptoms in clinical practice, although its effectiveness has not been scientifically proven. The addition of propolis has the potential to impart anti-inflammatory properties to cold cream. However, in high concentrations, propolis can trigger allergic reactions. Thus, the objective of this work was to develop a cold cream formulation based on purified beeswax containing the same amount of green propolis present in raw beeswax. The impact of adding this low propolis concentration to cold cream on AD control was evaluated in patients compared to cold cream without added propolis (CBlank). Raw beeswax was chemically characterized to define the propolis concentration added to the propolis-loaded cold cream (CPropolis). The creams were characterized as to their physicochemical, mechanical, and rheological characteristics. The effect of CPropolis and CBlank on the quality of life, disease severity, and skin hydration of patients with AD was evaluated in a triple-blind randomized preclinical study. Concentrations of 34 to 120 ng/mL of green propolis extract reduced TNF-α levels in LPS-stimulated macrophage culture. The addition of propolis to cold cream did not change the cream's rheological, mechanical, or bioadhesive properties. The preclinical study suggested that both creams improved the patient's quality of life. Furthermore, the use of CPropolis decreased the disease severity compared to CBlank.

SUBMITTER: Martin BA

PROVIDER: S-EPMC8466707 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Cutaneous microbiome effects of fluticasone propionate cream and adjunctive bleach baths in childhood atopic dermatitis.

Project description:Patients with atopic dermatitis (AD) are prone to skin infections, with microbes such as Staphylococcus aureus suspected of contributing to pathogenesis. Bleach baths might improve AD by reducing skin microbial burden.We sought to characterize the microbiota of lesional and nonlesional skin in young children with AD and control subjects and compare changes after treatment with a topical corticosteroid (TCS) alone or TCS + dilute bleach bath.In a randomized, placebo-controlled, single-blinded clinical trial in 21 children with AD and 14 healthy children, lesional and nonlesional AD skin was examined at baseline and after 4-week treatment with TCS alone or TCS plus bleach bath. Microbial DNA was extracted for quantitative polymerase chain reaction of predominant genera and 16S rRNA sequencing.At baseline, densities of total bacteria and Staphylococcus, including Staphylococcus aureus, were significantly higher at the worst AD lesional site than nonlesional (P = .001) or control (P < .001) skin; bacterial communities on lesional and nonlesional AD skin significantly differed from each other (P = .04) and from control (P < .001). After TCS + bleach bath or TCS alone, bacterial compositions on lesional skin normalized (P < .0001), resembling nonlesional skin, with microbial diversity restored to control skin levels.The 4-week time period and/or the twice-weekly baths may not have been sufficient for additional impact on the cutaneous microbiome. More detailed sequencing may allow better characterization of the distinguishing taxa with bleach bath treatment.Treatment with a TCS cream suffices to normalize the cutaneous microbiota on lesional AD; after treatment, bacterial communities on lesional skin resemble nonlesional skin but remain distinct from control.

| S-EPMC4992571 | biostudies-literature

Pimecrolimus cream 1% in the management of atopic dermatitis in pediatric patients: a meta-analysis.

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Effects of a novel formulation of fluocinonide 0.1% cream on skin barrier function in atopic dermatitis.

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| S-EPMC3156681 | biostudies-literature

Cytokine concentration across the stratum corneum in atopic dermatitis and healthy controls.

Project description:Tape stripping is a promising technique for assessment of epidermal biomarkers in inflammatory skin diseases. However, to facilitate its implementation in the clinical practice, a thorough validation regarding sampling strategy is needed. Knowledge of biomarkers variation in concentration across stratum corneum is scarce. Therefore, this study aimed to assess the variability of cytokines across stratum corneum using tape stripping technique by consecutive application of 21 adhesive tapes (D-squame) to lesional and non-lesional skin from 15 patients with atopic dermatitis (AD) and 16 healthy controls. Concentration of cytokines (IL-1α, IL-1b, IL-5, IL-18, IFN-γ, CCL17, CCL22, CCL27, CXCL8, CXCL10, TNF-α, TSLP, VEGFA) was determined in five different depths, using multiplex immunoassay. Comparing tape 4 with tape 21, no cytokine changed significantly in concentration in AD lesional skin. In AD non-lesional skin a small decrease was found for CCL17, CXCL8 and CXCL10. For healthy controls, a decrease was found for IL-1a, IL-1b, VEGFA and an increase for IL-18. Differences were found between AD skin and healthy control skin. Concentration of cytokines was stable across stratum corneum, indicating that sampling of only one tape from the stratum corneum is reliable in reflecting the overall cytokine milieu. Differences between AD and healthy skin confirm robustness of tape stripping for measuring cytokine levels.

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Clinical approach to the patient with refractory atopic dermatitis.

Project description: Not available

| S-EPMC8564861 | biostudies-literature

Atopic dermatitis.

Project description:Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.

| S-EPMC2883413 | biostudies-literature

Cream Cheese-Derived Lactococcus chungangensis CAU 28 Modulates the Gut Microbiota and Alleviates Atopic Dermatitis in BALB/c Mice.

Project description:Atopic dermatitis (AD) has a drastic impact on human health owing to complex skin, gut microbiota, and immune responses. Some lactic acid bacteria (LAB) are effective in ameliorating AD; however, the alleviative effects of dairy products derived from these LAB remain unclear. In this study, the efficacies of Lactococcus chungangensis CAU 28 (CAU 28) cream cheese and L. chungangensis CAU 28 dry cells were evaluated for treating AD in an AD mouse model. Overall, CAU 28 cream cheese administration was more effective against AD than L. chungangensis CAU 28 dry cells. Faeces from CAU 28 cream cheese-administered mice had increased short chain fatty acid, butyrate, acetate, and lactic acid levels, as well as butyrate-producing bacteria, including Akkermansia, Bacteroides, Lactobacillus, and Ruminococcus. Furthermore, oral CAU 28 cream cheese administration resulted in regulatory T cell (Treg)-mediated suppression of T helper type 2 (Th2) immune responses in serum and mRNA expression levels in the ileum. Oral CAU 28 cream cheese further reduced IgE levels, in addition to eosinophil and mast cell numbers. Therefore, CAU 28 cream cheese administration induced a coordinated immune response involving short-chain fatty acids and gut microbiota, indicating its potential for use as a supplement for AD mitigation.

| S-EPMC6345912 | biostudies-literature

Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies.

Project description:BackgroundPathogenesis of atopic dermatitis (AD) involves the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. A cream formulation of ruxolitinib, a potent selective JAK1/JAK2 inhibitor, was developed for topical delivery.MethodPharmacokinetic data were obtained from three double-blind, vehicle-controlled studies in patients with AD: a phase II study with ruxolitinib cream 0.15%, 0.5%, or 1.5% once daily or 1.5% twice daily (BID), and two phase III studies with 0.75% or 1.5% BID. Effects of baseline characteristics on pharmacokinetics were examined. Correlations were attempted between plasma concentrations and change in hematological parameters over time.ResultsRuxolitinib plasma concentrations at steady-state (Css) increased with cream strength in a less-than-dose-proportional manner. In the phase III studies, overall mean (standard deviation [SD]) Css after ruxolitinib cream 0.75% and 1.5% BID (23.8 [35.0] and 35.7 [55.0] nM) were a fraction of the half-maximal inhibitory concentration for thrombopoietin-stimulated phosphorylated STAT3 inhibition (281 nM), a JAK/STAT signaling marker. Three covariates were identified for Css: dose, percent body surface area (%BSA) treated, and baseline Investigator's Global Assessment score. Mean (SD) bioavailability of ruxolitinib cream 1.5% BID was 6.22% (7.66%). There were no correlations between Css and any hematological changes except for a transient increase in platelets at week 2.ConclusionsPlasma ruxolitinib concentrations after treatment with topical ruxolitinib cream in patients with up to 20% BSA affected by AD are not expected to lead to systemic plasma concentrations that may be associated with adverse effects commonly associated with oral JAK inhibitors. CLINICALTRIALS.GOV: NCT03011892; NCT03745638; NCT03745651.

| S-EPMC8200345 | biostudies-literature

Using a Machine Learning Approach to Identify Low-Frequency and Rare FLG Alleles Associated with Remission of Atopic Dermatitis.

Project description:Atopic dermatitis (AD) is a common relapsing inflammatory skin disease. FLG is the gene most consistently associated with AD. Loss-of-function variants in FLG have been previously associated with AD. Low-frequency and rare alleles (minor allele frequency < 5%) in this gene have been given less attention than loss-of-function variants. We fine sequenced the FLG gene in a cohort of individuals with AD. We developed a machine learning‒based algorithm to associate low-frequency and rare alleles with the disease. We then applied this algorithm to the FLG data, searching for associations between groups of low-frequency and rare FLG alleles and AD remission. A group of 46 rare and low-frequency FLG alleles was associated with increased AD remission (P = 2.76e-11). Overall, 16 of these 46 FLG variants were identified in an independent cohort and were associated with decreased AD incidence (P = 0.0007). This study presents an application of statistical methods in AD genetics and suggests that low-frequency and rare alleles may play a larger role in AD pathogenesis than previously appreciated.

| S-EPMC8659778 | biostudies-literature

Atopic dermatitis epidermis PCT-DIA

Project description:Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in AD pathogenesis, but the alterations in the proteome that occur in the entire epidermis have not been defined. Employing a pressure-cycling technology-data-independent acquisition (PCT-DIA) approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and non-lesional skin of AD patients. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry or by immunofluorescence staining. The identified proteins reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the epidermis. These results provide insight into the molecular alterations in the epidermis of AD patients and identify novel targets for pharmaceutical intervention.

2022-10-04 | PXD025431 | Pride

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