Search Results (1,184)

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by a complex and dynamic interplay between immune dysregulation and epidermal barrier dysfunction. Emerging evidence supports an integrated pathogenic model in which immune activation and barrier impairment form a bidirectional and self-reinforcing axis rather than representing separate processes. This review synthesizes current knowledge on the role of IL-4/IL-13-dependent signaling in regulating keratinocyte lipid metabolism and its impact on epidermal barrier integrity. IL-4/IL-13 signaling via the JAK-STAT pathway, particularly STAT6, contributes to keratinocyte dysfunction, resulting in impaired differentiation and coordinated alterations in lipid metabolism, including fatty acid elongation and ceramide synthesis. These cytokine-driven processes disrupt the organization of the stratum corneum lipid matrix, resulting in increased transepidermal water loss, enhanced skin permeability, and susceptibility to microbial colonization, thereby promoting chronic inflammation. Collectively, these findings support the concept that IL-4/IL-13-mediated dysregulation of keratinocyte lipid metabolism may represent an important immunometabolic mechanism linking type 2 inflammation with secondary barrier dysfunction in atopic dermatitis, thereby contributing to disease persistence. Targeting both immune pathways and epidermal lipid homeostasis may represent an effective strategy to restore barrier function and improve clinical outcomes. Full article

Background: Epidemiological data link hard and chlorinated water to atopic dermatitis (AD), but experimental evidence on their effect and on dermocosmetic benefit remains limited. Objectives: We aimed to compare the effects of soft, hard, and chlorinated water on atopic skin and assess whether a dermocosmetic routine mitigates these effects. Methods: In a 3-day, open-label, intra-individual study, 66 adults with atopic skin underwent repeated forearm immersions (five cycles/day) in soft, hard, or chlorinated water. One forearm received a cleansing-oil and moisturising-balm routine after each cycle; the contralateral forearm served as untreated control. TEWL, hydration, and global discomfort were assessed. In a 21-day real-life study, adults with AD regularly exposed to hard domestic or swimming-pool water used the routine daily. Discomfort and quality of life were recorded. Results: Water immersion induced modest, inconsistent TEWL changes, increased hydration and slightly reduced discomfort, without differences between water types. The routine reduced TEWL, increased hydration, and decreased discomfort for all water types. In real life, it produced immediate and sustained improvements in discomfort and quality of life. Conclusions: Under controlled exposure, soft, hard, and chlorinated water exert comparable, limited effects on atopic skin. The dermocosmetic routine consistently improves barrier-related parameters and comfort, independently of water type. Full article

The primary route of SARS-CoV-2 entry is via respiratory epithelium. However, many COVID-19 patients developed dermatological lesions, and SARS-CoV-2 RNA has been detected in the patients’ skin. Inflammatory skin diseases, psoriasis and atopic dermatitis (AD), significantly increased the risk of COVID-19. To evaluate the potential role of skin in SARS-CoV-2 host interactions, we utilized 3D human skin organoids (HSO) generated from human epidermal keratinocytes, as well as neonatal skin explants. HSO were treated with cytokines involved in acute and chronic skin inflammation and cytokine storm in severe COVID-19 disease: TNF-α, IL-6, IL-1β, and IFN-γ, individually and in combination. HSO were also treated with Th1 (TNF-α + IL-17) and Th2 (IL-4 + IL-13) cocktails inducing pro-psoriasis and pro-AD HSO changes, respectively. All individual cytokines, and especially their combinations, elevated the expression of ACE2 and TMPRSS2 at mRNA/protein levels. The Th2 cocktail induced only TMPRSS2, the Th1 cocktail predominantly induced ACE2. Topically applied Spike-pseudotyped lentiviral Tomato reporter, which binds ACE2 similarly to SARS-CoV-2, successfully transduced control and cytokine-treated HSO as well as neonatal skin explants. Cytokine treatment, especially TNF-α + IL-6 + IL-1β + IFN-γ and the Th1 cocktail, significantly increased viral entry. Transcriptomic analysis further revealed partial overlap between gene expression signatures induced by Spike-mediated entry in inflamed HSO and those observed in lung tissue from COVID-19 patients, supporting the biological relevance of skin models. Together, these findings demonstrate that inflammation may transiently alter the permissiveness of human skin to SARS-CoV-2 entry, suggesting that the skin may represent a previously underappreciated, although likely limited, interface in viral- host interactions. Full article

Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, whereas major depressive disorder is a common psychiatric condition with a substantial impact on quality of life; increasing attention has been given to oxidative and nitrosative stress as a potential biological link between these disorders. Methods: This narrative review synthesizes current evidence on molecular biomarkers of oxidative and nitrosative stress in AD and MDD and examines shared mechanisms within the skin–brain axis. Results: Across both conditions, studies consistently report increased markers of lipid peroxidation (e.g., malondialdehyde, 4-hydroxynonenal), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), and nitrosative stress, alongside impaired antioxidant defenses, particularly involving glutathione; these alterations are closely associated with chronic inflammation, cytokine signaling, mitochondrial dysfunction, and dysregulation of neuroimmune and hypothalamic–pituitary–adrenal axis pathways. Conclusions: Although the available evidence is heterogeneous and largely based on cross-sectional studies, limiting causal inference, the findings support a biologically plausible link between AD and depression mediated by shared redox pathways and highlight the need for further longitudinal and mechanistic research. Full article

The skin microbiome is essential for epidermal barrier integrity and immune homeostasis. This review explores the therapeutic shift in dermo-cosmetics toward probiotic, prebiotic, synbiotic, and postbiotic strategies for managing wound healing, “inflammaging”, and chronic dermatoses like acne, atopic dermatitis (AD), psoriasis, and rosacea. Mechanisms include gut–skin axis modulation, competitive pathogen exclusion, and the suppression of inflammatory pathways (e.g., NF-κB). While live probiotics demonstrate high clinical efficacy, their formulation is severely hindered by standard cosmetic preservatives and manufacturing thermal stress. Consequently, evidence suggests inanimate postbiotics have emerged as promising, stable alternatives, which may offer antimicrobial and tissue-repairing benefits without strict cold-chain requirements. However, the industry faces significant regulatory ambiguity and “probiotic-washing”, with most commercial products mislabeling postbiotic lysates as live cultures. Advancing this field requires standardized sampling protocols and transparent labeling. Ultimately, precision dermatology is likely to be driven by AI-assisted microbiome profiling, synthetic biology, and advanced delivery matrices (e.g., electrospun nanofibers, alginate microencapsulation), transforming skincare from reactive treatments into proactive, targeted ecological management. Full article

Background: Squalene is a key sebum lipid that plays an important role in skin barrier function, suppleness, and antioxidant protection. Age-related or disease-associated reductions in squalene levels—for example, in atopic dermatitis—reduce skin resilience and increase susceptibility to environmental stressors. However, its oxidation products can have inflammatory, comedogenic, and pro-aging effects on the skin, which is why adequate stabilization is essential when used in topical formulations. Objective: Therefore, identifying sustainable sources of stable squalene with beneficial skin-care properties is of considerable interest. Methods: This review employed an application-focused literature search and comparative analysis of established and new squalene sources, evaluating chemical composition, manufacturing processes, stability, and biological effects following topical applications based on predefined analytical criteria across peer-reviewed studies. Results: Silphium oil appears to be a promising novel source of highly concentrated, sustainable, and stable squalene with potential skin-conditioning properties at concentrations typically used in cosmetic products (2.1–12.6%) while preliminary formulation tests indicate emulsifiability even at concentrations up to 15%. It contains over 3% squalene, a fatty acid profile with over 66% PUFA, and negligible levels of oxidation byproducts (hexanal < 3 ppm) even after years of storage in various types of packaging. Although independent validation and broader comparative studies are limited, these results reveal new possibilities for the use of previously underutilized plant sources in skin care applications. Full article

Atopic dermatitis (AD) is a common chronic inflammatory condition of the skin that has increased dramatically over the past decade and significantly impacts individual quality of life. Corticosteroids are still the primary therapy for AD, but there are limitations to their continued use due to potential adverse effects, particularly when used in sensitive areas. Topical calcineurin inhibitors (CNIs), such as tacrolimus and pimecrolimus, are available as a safe, steroid-sparing alternative that directly inhibit calcineurin-mediated activation of T cells and have been shown to be efficacious according to varying clinical study designs including randomized controlled trials, registry studies and meta-analyses. Although there was controversy regarding the safety of CNIs subsequent to the FDA’s black-box warning in 2006, the preponderance of evidence supports their continued safety when used as directed. In contrast to biologics and JAK inhibitors, CNIs occupy an inherently unique therapeutic niche for use in pediatric patients, have demonstrated historical efficacy, and can provide localized affordable treatment in sensitive areas including the face, eyelids and intertriginous surfaces. Furthermore, the role of CNIs in the context of precision dermatology continues to be defined through new innovations including barrier-repair strategies used in combination with topical medications, microneedle systems, and nanocarrier formulations. Hence, the role of CNIs in the current AD treatment paradigm is crucial and lies at the interface between topical corticosteroids and systemic immunomodulatory agents. The narrative review discusses recent advances in formulation strategies, combination approaches, and targeted delivery systems, underscoring how CNIs continue to bridge established practice and emerging therapeutic innovation in AD. Full article

Skin health depends on the coordinated maintenance of barrier integrity, immune homeostasis, redox balance, microbial ecology, and systemic metabolic status. Among dietary constituents, polysaccharides have attracted increasing attention because they represent a structurally heterogeneous class of complex carbohydrates whose biological behavior is shaped by molecular weight, monosaccharide composition, glycosidic linkage patterns, branching, higher-order conformation, and physicochemical properties. However, many current skin-related studies remain primarily phenomenon-driven, with insufficient attention to how specific structural features influence biological function and dermatologic relevance. From a structure–function perspective, key structural features of dietary polysaccharides may influence several skin-relevant biological processes, including microbiota-associated signaling, immune regulation, barrier homeostasis, oxidative balance, and extracellular matrix protection. The relevance of these structure-linked functions differs across dermatologic contexts: it appears most direct in photoaging, more conditional in atopic dermatitis, and relatively indirect in psoriasis, whereas wound-repair-related settings are less closely aligned with strict dietary relevance. Current evidence therefore supports structure–function associations more strongly than direct associations between specific structural features and dermatologic outcomes. Dietary polysaccharides are not functionally interchangeable in skin-related contexts, and their skin-related effects depend on structural background, disease setting, and mode of application. Where non-dietary evidence is discussed, it serves primarily as mechanistic or translational contextualization rather than as a basis for nutritional recommendation. Clarifying these relationships may support future mechanistic research and facilitate more rational nutritional applications of dietary polysaccharides in skin health. Full article

Emerging research highlights the complex interplay between the gut microbiome, skin health, and environmental exposures, forming what is now recognized as the gut–skin–exposome axis. This narrative review explores the role of gut microbiome dysbiosis—a disruption in the balance of intestinal microorganisms—in the pathogenesis and progression of various non-communicable inflammatory skin diseases, including acne, atopic dermatitis, psoriasis, rosacea, systemic lupus erythematosus, chronic spontaneous urticaria, hidradenitis suppurativa, and alopecia areata. This review synthesizes mechanistic studies, clinical trials, and Mendelian randomization data to elucidate how altered gut microbial composition contributes to systemic and cutaneous inflammation. Key modifiable factors, such as diet, antibiotics, stress, and sleep, as well as interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, are discussed for their potential therapeutic value. By integrating clinical insights with microbiome science, this review underscores the importance of a holistic, systems-based approach in managing inflammatory skin diseases, offering clinicians evidence-based strategies to improve patient outcomes through gut microbiome modulation. Full article

Background: Atopic dermatitis (AD) is a widespread, chronic inflammatory skin condition with substantial global impact. While regional studies have explored its prevalence in Spain, comprehensive national data detailing AD prevalence across various sociodemographic groups remain limited. Objective: This study aimed to estimate the 2023 prevalence of AD in Spain and explore disparities across key sociodemographic groups. Methods: We conducted a retrospective cross-sectional study using Spain’s National Health System Primary Care Clinical Database (BDCAP). We identified AD cases via ICPC code S87. We calculated crude and age-standardized prevalence rates (ASPRs) and rate ratios, stratified by sex, age, country of origin, municipality size, income, and employment status. The 2013 European Standard Population was used for age standardization. Results: In 2023, an estimated 2,706,675 individuals in Spain were living with AD, with women (1,451,216 cases) experiencing a higher burden than men (1,255,459 cases), and also presenting with a higher mean age (27.23 years vs. 22.96 years for men). Urban living showed a clear dose–response relationship with AD prevalence. In cities with over 500,000 inhabitants, ASPRs reached 7.74% in men and 8.52% in women; significantly higher than in rural areas, where rates were 5.66% and 6.57%, respectively. Individuals in the middle-income bracket (€18,000–€99,999) consistently exhibited the highest prevalence, and the non-active employment group also demonstrated an elevated risk (ASPRs: 6.51% for men, 7.28% for women). Finally, Spanish-born individuals generally had higher AD prevalence compared to most foreign-born populations. Conclusions: Atopic dermatitis in Spain displays significant sociodemographic disparities, with urban environments, female sex, and non-active employment status emerging as key risk factors. These findings underscore the importance of targeted public health interventions and equity-focused dermatological planning. Full article

Maintaining a balanced skin microbiota is essential for preserving epidermal barrier integrity and overall skin health. Dysbiosis, particularly the opportunistic overgrowth of Staphylococcus aureus, is associated with barrier dysfunction and inflammatory dermatoses such as atopic dermatitis, psoriasis, and acne. In dysbiotic states, microbial regulatory mechanisms become disrupted, enabling pathogenic strains to proliferate and release proteases that degrade structural components of the skin barrier, increasing epidermal permeability in a manner analogous to ‘leaky gut’ physiopathology. Microbiota dysbiosis has further been proposed as an emerging hallmark of aging, contributing to chronic low-grade inflammation, impaired tissue repair, and progressive barrier decline. Current strategies predominantly target the microbiota itself, leaving the host tissue response to protease-mediated barrier disruption comparatively underaddressed. To fill this gap, an ex vivo human skin model was developed based on topical application of purified S. aureus serine protease SspA to skin explants, enabling controlled investigation of early host–microbiota interaction events. Barrier function, junctional integrity, inflammatory mediators, and proteostasis were assessed through a panel of complementary biomarkers—Lucifer Yellow permeability, claudin-1, desmoglein-1, filaggrin, IL-31, S100A8/A9, PGE2, and protein carbonylation. SspA induced measurable barrier disruption, junctional protein loss, inflammatory mediator upregulation, and proteostasis impairment without overt tissue damage. A biotic culture filtrate of Bifidobacterium adolescentis partially attenuated SspA-induced protein carbonylation. This model provides the scientific community with a controlled, biologically relevant platform for identifying biomarkers of early barrier impairment and evaluating host-targeted interventions aimed at preventing or counteracting protease-driven barrier damage in dysbiosis-associated skin conditions. A better understanding of the early molecular mechanisms through which microbial virulence factors drive barrier disruption and proteostasis decline may further contribute to broader strategies aimed at preserving skin integrity during aging. Full article

Background: Biofilms consist of complex microbial communities embedded in an extracellular matrix which confer resistance to the most used antimicrobial agents. Chronic wounds are often associated with burns, trauma, surgery, diabetes and peripheral vascular disease. They are characterized by a marked delay in wound healing favoring the development of microbial biofilms, which in turn further delay tissue regeneration. Staphylococcus aureus, Staphylococcus epidermidis, and methicillin-resistant staphylococci biofilms are found in chronic wounds, seriously hindering wound treatment. Vitreoscilla filiformis, a Gram-negative non-pathogenic filamentous bacterium, has been shown to improve atopic dermatitis by reducing S. aureus colonization and inducing antioxidant responses in the skin. Objectives: The aim of the present study was to evaluate the antimicrobial, anti-inflammatory, and regenerative activities of the V. filiformis supernatant (VFS). Methods: The effect of VFS on bacteria growth was assessed by microbial growth kinetics and biofilm formation and dispersal. Antioxidant potential was determined by DPPH-scavenging ability and reduction in intracellular reactive oxygen species (ROS). The regenerative properties were assessed by scratch assay. Results: V. filiformis VFS holds strong anti-biofilm activity against S. aureus, S. epidermidis and methicillin-resistant S. aureus (MRSA), acting during both biofilm formation and dispersion. The decrease in biofilm mass is accompanied by a significant increase in the planktonic form compared to the untreated cells. Moreover, VFS is characterized by an interesting antioxidant activity, as demonstrated by a cell-free DPPH assay and a neutrophil-based in vitro assay. In addition, VFS can stimulate tissue regeneration in human dermal fibroblasts and keratinocytes. Conclusions: The demonstration of anti-biofilm, antioxidant and regenerative properties of V. filiformis supernatant could be exploited for the treatment of biofilm-associated wound infections. Full article

Background: Eczema, atopic dermatitis, and urticaria are common pediatric inflammatory skin diseases, but serum vitamin profiles across these diseases remain poorly characterized. Objectives: To compare demographic characteristics, serum vitamin levels, and vitamin insufficiency rates among children with these diseases, and to identify independent factors associated with disease presence. Methods: This retrospective study included 504 children: 43 with eczema, 43 with atopic dermatitis, 40 with urticaria, and 378 healthy controls. Serum levels of nine vitamins were measured by electrochemical assays. Univariable and multivariable logistic regression analyses were used to identify associated factors with false discovery rate correction. Propensity score matching based on age and sex was additionally performed for each disease-control comparison, followed by matched regression analyses. An exploratory nomogram was developed and evaluated. Results: The mean age of the cohort was 6.26 years, and 50.2% were male. Vitamin B9 insufficiency was the most prominent abnormality, occurring more frequently in the overall disease group than in controls (17.5% vs. 0.3%, p < 0.001). Vitamin D insufficiency appeared more frequently in the urticaria group than in controls (42.5% vs. 28.3%, p = 0.062). In multivariable analyses after PSM, vitamin B9 insufficiency and lower vitamin B6 levels remained independently associated with all three diseases. Conclusions: Pediatric inflammatory skin diseases exhibited distinct vitamin profiles relative to healthy controls, with vitamin B9 insufficiency emerging as a common feature across eczema, atopic dermatitis, and urticaria. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by oxidative stress and impaired skin barrier function. These pathological features contribute to persistent inflammation and symptom exacerbation, highlighting the need for therapies that can both reduce oxidative stress and modulate inflammatory pathways. Methods: Ulmus pumila Linné (Ulmi) was prepared via hot water extraction and tested for cytotoxicity, antioxidant activity, and anti-inflammatory effects in HaCaT keratinocytes stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). In vivo efficacy was assessed using a 2,4-dinitrochlorobenzene (DNCB)-induced AD model in SKH-1 hairless mice. Bioactive compounds were identified using liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS), and molecular docking analysis was performed to evaluate the binding affinity of these compounds to aldehyde dehydrogenase 2 (ALDH2). Results: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays confirmed that Ulmi was safe at concentrations up to 400 μg/mL. In TNF-α/IFN-γ-stimulated HaCaT cells, Ulmi significantly upregulated ALDH2 expression in a dose-dependent manner and reduced reactive oxygen species (ROS) production. The extract also suppressed pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), while inhibiting the activation of nuclear factor kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. In the AD mouse model, Ulmi treatment improved clinical skin scores, reduced epidermal thickness, and decreased inflammatory markers compared to untreated controls. LC-QTOF-MS/MS analysis identified eight bioactive compounds, with procyanidin B2, catechin, and epicatechin as major constituents. Molecular docking revealed that procyanidin B2 had the strongest binding affinity to ALDH2 (−9.5 kcal/mol). Conclusions: These findings demonstrate that Ulmi effectively ameliorates AD-like symptoms through ALDH2-mediated antioxidant mechanisms and anti-inflammatory effects. The results suggest that Ulmi may serve as a promising natural therapeutic agent for the management of atopic dermatitis. Full article

Canine atopic dermatitis (AD) is a common allergic skin disease for which identifying allergen sensitization via IgE serological or intradermal testing is necessary to implement allergen-specific immunotherapy. Because serum IgE has a short half-life and circulating levels fluctuate with environmental allergen exposure, the timing of blood sampling may influence serological test outcomes. This cross-sectional study assessed seasonal variation in allergen-specific IgE concentrations and seropositivity rates across pollen and mite allergen categories in Scandinavian dogs suspected of allergic disease. PAX multiplex macroarray results from 5014 canine sera submitted by veterinarians across Denmark, Norway, and Sweden over one full year were retrospectively analyzed for 17 allergens, including tree, grass, and weed pollens, house dust mites, and storage mites. Mean sIgE levels showed statistically significant but relatively small seasonal variation. Seropositivity rates, however, showed clearer patterns: seropositivity for tree and weed pollen was highest in spring and summer, and that for house dust mite peaked in autumn and winter, while storage mite sensitization rates showed the opposite trend. These results confirm that IgE serological test results in dogs are affected by the sampling season and emphasize the importance of considering timing when collecting and interpreting IgE serological tests in atopic dogs. Full article