Inflammatory Skin Disease Research Articles

Plasma-Activated AVC Hydrogel for Reactive Oxygen and Nitrogen Species Delivery to Treat Allergic Contact Dermatitis.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease that accounts for approximately 20% of all occupational skin diseases. As an adverse and recurrent inflammatory dermatological agent, ACD shows insufficient response to current therapies largely owing to abnormal inflammatory activation and accompanying bacterial infection in lesions. Cold atmospheric plasma is a noninvasive fledgling reactive oxygen and nitrogen species (RONS)-based therapeutic technique for ACD treatment; however, its clinical adoption has been hindered due to the risk of electrical burns and insufficient delivery of the plasma-generated RONS. To address these limitations, we constructed plasma-activated AVC (PA-AVC) hydrogels loaded with plasma-generated RONS for ACD treatment as an alternative to the common direct plasma irradiation treatment. The proposed PA-AVC hydrogels were produced on a biodegradable acryloyldimethylammonium taurate/VP copolymer (AVC) with the aid of a novel air discharge plasma without the involvement of any catalyst. In vitro data showed that abundant RONS were produced and incorporated into the PA-AVC hydrogels via complex gas-liquid reactions between the air discharge plasma and hydrosolvent; additionally, the PA-AVC hydrogels exhibited excellent storage, slow release and transdermal delivery of RONS as well as good antibacterial effects. Moreover, in vivo experiments demonstrated that PA-AVC hydrogels effectively alleviated the ACD symptoms, such as skin redness and swelling, reduced epidermal thickening and inhibited mast cell infiltration and IL-9, TNF-α, and TSLP expression with no evident systemic toxicity. Our results revealed that long-acting plasma-activated AVC hydrogels could be effective therapeutic agents for local ACD treatment.

Antioxidative and Anti-Atopic Dermatitis Effects of Peptides Derived from Hydrolyzed Sebastes schlegelii Tail By-Products.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

Therapeutic potential of plasma-treated solutions in atopic dermatitis

Atopic Dermatitis (AD) is a prevalent inflammatory skin disease that is currently incurable. Plasma-treated solutions (PTS) (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as novel therapy. Recently, PTS is gaining attention due to its advantages over non-thermal plasma (also known as cold atmospheric plasma). Thus, we explore the application of PTS in treating AD. In vivo experiments demonstrated that PTS significantly alleviated AD-like symptoms. It reduced mast cell and macrophage infiltration, decreased scratching times and serum IgE levels. These therapeutic effects of PTS on AD mice were associated with the activation of the antioxidant molecule Nrf2. In vitro experiments revealed that PTS could decrease ROS level and regulate cytokine expression (such as IL-6, IL-10, IL-13 and CCL17) in TNF-α/IFN-γ-stimulated keratinocytes and LPS-stimulated M1 macrophages. Additionally, PTS could upregulate the expression of antioxidant stress molecules such as Nrf2, HO-1, NQO1 and PPAR-γ in both cell types. Overall, PTS demonstrated potent therapeutic potential for AD without notable side effects. Our research provided a promising approach to AD treatment and may serve as a potential therapeutic strategy in other inflammatory skin diseases.

H Antigen expression modulates epidermal Keratinocyte Integrity and differentiation

BackgroundABO blood group antigens (ABH antigens) are carbohydrate chains glycosylated on epithelial and red blood cells. Recent findings suggest reduced ABH expression in psoriasis and atopic dermatitis, a chronic inflammatory skin disease with retained scale. H antigen, a precursor for A and B antigens, is synthesized by fucosyltransferase 1 (FUT1). Desmosomes, critical for skin integrity, are known to require N-glycosylation for stability. We investigate the impact of H antigens, a specific type of glycosylation, on desmosomes in keratinocytes.MethodPrimary human keratinocytes were transfected with FUT1 siRNA or recombinant adenovirus for FUT1 overexpression. Cell adhesion and desmosome characteristics and their underlying mechanisms were analyzed.ResultThe knockdown of FUT1, responsible for H2 antigen expression in the skin, increased cell-cell adhesive strength and desmosome size in primary cultured keratinocytes without altering the overall desmosome structure. Desmosomal proteins, including desmogleins or plakophilin, were upregulated, suggesting enhanced desmosome assembly. Reduced H2 antigen expression via FUT1 knockdown led to increased keratinocyte differentiation, evidenced by elevated expression of differentiation markers. Epidermal growth factor receptor (EGFR) has been described to be associated with FUT1 and promotes cell migration and differentiation. The effects of FUT1 knockdown were recapitulated by an EGFR inhibitor concerning desmosomal proteins and cellular differentiation. Further investigation demonstrated that the FUT1 knockdown reduced EGFR signaling by lowering the levels of EGF ligands rather than directly regulating EGFR activity. Moreover, FUT1 overexpression reversed the effects observed in FUT1 knockdown, resulting in the downregulation of desmosomal proteins and differentiation markers while increasing both mRNA and protein levels of EGFR ligands.ConclusionThe expression level of FUT1 in the epidermis appears to influence cell-cell adhesion and keratinocyte differentiation status, at least partly through regulation of H2 antigen and EGFR ligand expression. These observations imply that the fucosylation of the H2 antigen by FUT1 could play a significant role in maintaining the molecular composition and regulation of desmosomes and suggest a possible involvement of the altered H2 antigen expression in skin diseases, such as psoriasis and atopic dermatitis.

Epidemiology and Healthcare of Juvenile and Late-Onset Acne: Claims Data Analysis.

Acne is the most frequent chronic inflammatory skin condition in adolescence but occurs also in later age. Our study aimed to characterise the epidemiology, geographical distribution, comorbidity and healthcare of acne juvenilis (AJ) and acne tarda (AT). Statutory health insurance (SHI) data from 2016 to 2020 were analysed. Prevalence rates, including geographical distribution, comorbidities and drug use by specialists group, were measured. In 2020, the prevalence of acne among adults was 1.50% (AT > 25years) and among adolescents was 3.88% (AT ≤ 25years). The highest prevalence (13.02%) was observed at the age of 17 years. Sex differences were higher in AT (73.80% in women) than in AJ (64.55% in women). Compared with non-affected persons, individuals with acne - in particular with AT - showed significantly higher rates of skin-related comorbidities, including folliculitis (rate ratio (RR) 8.89), pyoderma (RR 7.27) and rosacea (RR 5.53), and non-skin-related comorbidities, such as ovarian dysfunction (RR 2.36), rhinitis allergica (RR 1.84) and Crohn's disease (RR 1.79). Preferred systemic therapeutics prescribed were anti-infectives in AT (46.86%) and retinoids in AJ (52.35%). In the majority of cases, dermatologists were involved in the treatment of acne (AT 65.77%; AJ 76.27%). The most commonly prescribed topical agents were adapalene with benzoyl peroxide (AT 87.72%; AJ 85.75%), while systemic isotretinoin (AT 81.20%; AJ 90.06%) was also a frequently used drug. General practitioners were more likely to prescribe anti-infectives, especially topical antibiotics such as chlortetracycline (AT 52.38%; AJ 44.44%) and systemic antibiotics, especially tetracycline (AT 58.33%; AJ 67.50%). Acne affects a relevant proportion of the German population not only in adolescence, and management of this inflammatory skin disease does not naturally follow medical guidelines or specialist recommendations. These findings emphasise the importance of specialised care and comprehensive therapeutic management that should also consider the exploration of comorbidities.

NLRP10 maintains epidermal homeostasis by promoting keratinocyte survival and P63-dependent differentiation and barrier function

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and aberrant immune responses. Despite recent developments in new therapeutics for AD, there is still a large unmet medical need for disease management due to the complex and multifactorial nature of AD. Recent genome-wide association studies (GWAS) have identified NLRP10 as a susceptible gene for AD but the physiological role of NLRP10 in skin homeostasis and AD remains unknown. Here we show that NLRP10 is downregulated in AD skin samples. Using an air-lift human skin equivalent culture, we demonstrate that NLRP10 promotes keratinocyte survival and is required for epidermal differentiation and barrier function. Mechanistically, NLRP10 limits cell death by preventing the recruitment of caspase-8 to the death inducing signaling complex (DISC) and by inhibiting its subsequent activation. NLRP10 also stabilizes p63, the master regulator of keratinocyte differentiation, to drive proper keratinocyte differentiation and to reinforce the barrier function. Our findings underscore NLRP10 as a key player in atopic dermatitis pathogenesis, highlighting NLRP10 as a potential target for therapeutic intervention to restore skin barrier function and homeostasis in AD.

Association Of Eosinophil And Total Ige Values With Allergy Test Results In Patients With Atopic Dermatitis

AOBJECTIVES: Atopic dermatitis (AD) is a chronic, recurrent, allergic inflammatory skin disease that may have a genetic predisposition. Eosinophilia is a common finding in patients with atopy. In our study, we aimed to investigate the relationship between eosinophil and IgE levels and allergy test results in patients with atopic dermatitis. METHODS: In this descriptive study, the files of patients diagnosed with atopic dermatitis and followed up in our Pediatric Allergy and Immunology Clinic between January 2021 and December 2022 were retrospectively reviewed. Age, gender, eosinophil, total IgE and specific IgE (for food and inhaled allergens) values were analyzed in the study. Skin prick test (SPT) was also performed in patients who had negative results for allergen-specific IgE. RESULTS: The absolute eosinophil count, eosinophil (%) and total IgE values of patients sensitized to at least one of the food and aeroallergens were significantly higher than those without allergen sensitization. The cut-off point of total IgE in predicting allergen sensitization was found to be 91.5 by ROC analysis. The sensitivity and specificity values for the cut-off point of total IgE were 73.3% and 72.9%. CONCLUSION: In this study, allergen sensitization was detected in 3 out of every 4 AD patients with total IgE and eosinophil values above the cut-off point we analyzed. Accordingly, we think that total IgE and eosinophil values are successful in predicting allergen sensitization. In clinics where specific IgE or SPT cannot be performed, eosinophil and total IgE values in whole blood will be useful for preliminary diagnosis.

Psoriasis management tree based on comorbidity.

Psoriasis, a common chronic inflammatory skin disorder, encompasses various subtypes, including guttate, pustular, erythrodermic, and the most common type, plaque psoriasis. Irrespective of the subtype, psoriasis can manifest with multisystemic presentations, including psoriatic arthritis, metabolic disorders, cardiovascular disease, malignancies, chronic kidney disease (CKD), psychiatric illness, and inflammatory bowel disease (IBD). Many comorbidities and concomitant conditions must be considered when selecting the most appropriate therapy for a patient (Kaushik etal., 2019 and Monks etal., 2021) . Ongoing clinical trials and the development of new therapeutic targets contribute to the continuous improvement of available treatment options. Given the dynamic landscape of therapies, particularly when managing complex patients with multiple comorbidities, dermatologists are constantly challenged with the task of adeptly tailoring treatments to each psoriasis patient. This article systematically reviews the current evidence, presenting it as an updated Psoriasis Decision Tree to assist physicians in selecting tailored treatment options.

Discovery of Janus Kinase and Histone Deacetylase Dual Inhibitors as a New Strategy to Treat Psoriasis.

Psoriasis is a common, chronic, recurrent, and inflammatory skin disease, which causes physical and psychological problems in patients and lacks effective and economic therapeutics. Herein, we designed Janus kinase (JAK) and histone deacetylase (HDAC) dual inhibitors as a new strategy for the treatment of psoriasis. In particular, compound 11i was identified with excellent inhibitory activity toward JAKs (JAK2 IC50 = 0.49 nM) and HDACs (HDAC6 IC50 = 12 nM). Moreover, it exhibited potent activities in inhibiting the proliferation of TNF-α-induced HaCAT cells and the production of nitric oxide. Importantly, compound 11i significantly ameliorated psoriasis-like skin lesions in an imiquimod-induced murine model with low toxicity, which was superior to JAK inhibitor momelotinib, HDAC inhibitor vorinostat, and their combination. This work provided a proof-of-concept for JAK/HDAC dual inhibitors as a promising strategy for the treatment of psoriasis.

Evaluating the Effectiveness of Probiotic Supplementation in Combination With Doxycycline for the Treatment of Moderate Acne: A Randomized Double-Blind Controlled Clinical Trial.

Acne is a chronic inflammatory skin disease that negatively affects patients' quality of life. Increasing antibiotic resistance is making acne less responsive to treatment. Probiotics are live microorganisms that can provide health benefits by fighting pathogens and maintaining intestinal homeostasis and skin microbiome balance. This study investigates the effects of probiotics in the treatment of acne vulgaris. In this randomized controlled clinical trial, 80 patients with moderate acne were divided into two groups of 40. All patients received the same topical treatment, which consisted of a daily antibacterial face wash and Adapalene gel every other night. The control group received one capsule of doxycycline (100 mg) daily, whereas the intervention group received one probiotic capsule daily in addition to doxycycline. Patients underwent photography of facial acne lesions, and treatment response was assessed using the global acne grading system (GAGS) and acne grading method at baseline, as well as during follow-up visits at 1, 2, and 3 months. The global acne grading system indicated that both groups showed improvement. However, analyses revealed that outcomes were significantly better in the doxycycline plus probiotics group for the forehead (p = 0.018), chin (p = 0.021), and nose (p = 0.021). No significant differences were observed for the left and right cheeks, back, and chest areas, with the mean GAGS score reduction between the two groups differing by only 2%. Treatment with probiotics significantly reduced the severity of lesions compared to the control group (p < 0.001). The acne grading method also indicated that the intervention group had a significantly better treatment response than the control group (p < 0.001). Furthermore, treatment with probiotics did not result in any side effects. Probiotics can serve as an effective and safe treatment option, enhancing the outcomes of routine acne treatments, particularly for patients with acne on the forehead, chin, and nose.

Ferulic Acid in the Treatment of Papulopustular Rosacea: A Randomized Controlled Study.

Rosacea is a chronic inflammatory skin disease characterized by flushing, erythema, papules, and pustules on the central face. It affects patient appearance and is noted for its chronicity, recurrence, and resistance to treatment. Effective rosacea treatment requires repairing the skin barrier, reducing inflammation, and promoting vasoconstriction. This study aims to evaluate the efficacy of topical ferulic acid in treating papulopustular rosacea and its impact on skin barrier function. Sixty patients with mild to moderate papulopustular rosacea were selected from the Department of Dermatology at the Affiliated Hospital of Shandong Second Medical University between January 2023 and December 2023. Patients were randomly assigned to either a control group or an observation group, with 30 patients in each group. The observation group applied ferulic acid solution to the affected areas, while the control group used normal saline, both twice daily for 6 weeks. Both groups also received 0.1 g doxycycline hydrochloride tablets orally once daily. Skin lesions and skin barrier function were assessed using VISIA imaging and self-rating scales before and during treatment, and adverse reactions were recorded. After 6 weeks, both skin lesion assessments and self-assessment scores improved significantly from baseline, with greater improvement in the observation group compared to the control group (p < 0.05). Indicators of skin barrier function and VISIA imaging results demonstrated the efficacy of ferulic acid in treating rosacea. The total effective rate was significantly higher in the observation group (80.00%) compared to the control group (63.33%) (p < 0.05). In the observation group, nine patients (30.00%) experienced a greasy sensation initially, one patient (3.33%) reported tingling and itching, and no serious adverse reactions were observed. Ferulic acid is effective as an adjuvant treatment for papulopustular rosacea, significantly improving skin lesions and repairing skin barrier function with minimal adverse reactions.

Efficacy and Potential Mechanisms of Naringin in Atopic Dermatitis

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases. Topical treatments are recommended for all patients regardless of severity, making it essential to develop an effective topical AD treatment with minimal side effects; We investigated the efficacy of topical application of naringin in AD and explored the possible mechanisms using an AD mouse model induced by 1-chloro-2,4-dinitrobenzene (DNCB). Clinical, histological, and immunological changes related to AD and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling proteins in the skin tissues were measured as outcomes; Naringin treatment resulted in a significant improvement in dermatitis severity score and reduced epidermal thickness and mast cell count in the skin (p &lt; 0.05). Naringin also demonstrated the ability to inhibit DNCB-induced changes in interleukin (IL) 4, chemokine (C-C motif) ligand (CCL) 17, CCL22, IL1β, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels by quantitative real-time polymerase chain reaction (qRT-PCR) and IL13 by enzyme-linked immunosorbent assay (ELISA) (p &lt; 0.05). Western blot results exhibited the decreased JAK1, JAK2, STAT1, STAT3, phospho-STAT3, and STAT6 expression in the naringin-treated groups (p &lt; 0.05); The findings of this study suggest that topical naringin may effectively improve the symptoms of AD and could be used as a therapeutic agent for AD.

Systemic Therapy for Atopic Dermatitis in Children and Adolescents: A United States Expert Consensus.

Atopic dermatitis (AD) is a chronic, type-2 mediated, inflammatory skin disease characterized by intense pruritus, disruption of skin barrier function, and immune dysregulation. Management strategies for AD are routinely determined based on disease severity. First-line treatment begins with basic skin care and topical anti-inflammatory medication, which is typically sufficient for the management of mild-to-moderate disease. For those patients with moderate-to-severe disease, systemic therapy is often required. This can involve off-label treatment with conventional immunosuppressant medications. However, this approach is limited by a lack of robust clinical trial data and safety concerns that necessitate close monitoring. The emergence of novel targeted biologics and small molecules to treat AD presents an opportunity to optimize AD management and patient outcomes by offering greater efficacy than traditional immunosuppressants and a favorable safety profile. As the treatment landscape shifts, clinicians can benefit from a standardized process of patient assessment and treatment, along with resources to help maintain contemporary knowledge of available therapeutic options. This United States (US)-based, expert-led consensus used a modified Delphi process to develop core recommendations for the use of systemic medications for the management of pediatric patients &lt;18 years of age with moderate-to-severe AD.

Exploring the association between skin microbiota and inflammatory skin diseases: a two-sample Mendelian randomization analysis.

Dysbiosis in the skin microbiome is closely associated with various inflammatory skin diseases. However, current research on the causal relationship between the skin microbiome and inflammatory skin diseases lacks comprehensive and detailed investigation. We used a two-sample Mendelian randomization (MR) approach to explore associations between the skin microbiome and seven inflammatory skin diseases, including acne, atopic dermatitis, erysipelas, vitiligo, psoriasis, rosacea, and urticaria. The GWAS summary data for the skin microbiome was derived from 647 participants in two German population-based cohorts, and for the inflammatory skin diseases, they were sourced from the FinnGen consortium. Our primary MR analysis method was the inverse variance weighted (IVW) method, complemented by alternatives like MR-Egger regression, weighted median estimation, and constrained maximum likelihood. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and MR-PRESSO outlier detection, were conducted to validate and stabilize our findings. We identified significant causal relationships between the skin microbiome and seven inflammatory skin diseases: acne, atopic dermatitis, erysipelas, vitiligo, psoriasis, rosacea, and urticaria, with 7, 6, 9, 1, 7, 4, and 7 respective causal relationships for each disease. These relationships comprise 20 protective and 14 risk causal relationships. We applied the false discovery rate correction to these results. Sensitivity analysis revealed no significant pleiotropy or heterogeneity. Our study revealed both beneficial and detrimental causal relationships between diverse skin microbiota and inflammatory skin diseases. Additionally, the ecological niche of the skin microbiome was crucial to its functional impact. This research provided new insights into how skin microbiota impacted skin diseases and the development of therapeutic strategies.

A Mendelian randomization analysis of inflammatory skin disease risk due to mineral deficiencies.

Mineral deficiencies, such as iron (Fe), zinc (Zn), and selenium (Se), play crucial roles in inflammation and immune responses and are linked to chronic inflammatory skin diseases. This study used genome-wide association study (GWAS) data and Mendelian randomization (MR) to investigate the genetic causality among serum levels of five minerals (Fe, Cu, Zn, Se, Ca), three iron metabolism indicators (TSAT, TIBC, ferritin), and three chronic inflammatory skin diseases [psoriasis (PS), atopic dermatitis (AD), acne vulgaris (AV)]. Two-sample MR analyses using the "TwoSample MR" package in R were conducted with aggregate outcome data from the FinnGen database. The inverse-variance-weighted (IVW) method was applied to assess causal relationships between mineral levels and disease outcomes. Robustness was examined via heterogeneity and pleiotropy tests. IVW analysis showed significant association between blood transferrin saturation (TSAT) and PS (p = 0.004, OR = 1.18). Serum Zn and Se levels showed inverse correlation with AD (p = 0.039, OR = 0.92). However, due to limited SNPs, robustness was reduced. TSAT is genetically linked to PS, highlighting iron homeostasis in disease development. Zn and Se intake may reduce AD risk.

Exploring racial and ethnic disparities in the hidradenitis suppurativa patient disease journey: Results from a real-world study in Europe and the USA.

Hidradenitis suppurativa (HS) is an inflammatory skin disease associated with high morbidity and disability that has limited treatment options. People from racial and ethnic minority groups may experience greater disease severity and delay to diagnosis. This study assessed the impact of race/ethnicity on HS diagnosis and management in real-world clinical settings. Data were derived from the Adelphi Real World Hidradenitis Suppurativa Disease Specific Programme, a survey of dermatologists and their consulting HS patients in five European countries and the USA in 2020/2021. Dermatologists returned demographic and clinical data, and treatment goals and satisfaction for their next five to seven consulting patients. Patients completed a questionnaire on disease history and diagnosis, disease burden, and treatment satisfaction. Groups were compared with bivariate tests. In total, 312 physicians returned data on 1787 patients; 57.6% were female and 77.7% White. People from racial and ethnic minority groups were younger than White patients (32.9 ± 11.6 vs. 34.9 ± 12.4, mean ± standard deviation) and reported symptoms at a younger age (23.3 ± 10.8 vs. 26.2 ± 11.1), but their time to first consultation was longer than for White patients (2.6 ± 5.7 vs. 1.2 ± 2.5 years). People from racial and ethnic minority groups took longer to receive a correct diagnosis following first consultation (2.7 ± 5.3 vs. 1.5 ± 4.1 years) and were more likely to be misdiagnosed with boils (73.5% vs. 40.4%). People from racial and ethnic minority groups had a greater disease awareness at diagnosis and reported wanting greater support. People from racial and ethnic minority groups reported a greater impact on life, more severe pain, and a greater level of activity impairment in the Work Productivity and Activity Impairment: General Health (27.0 ± 25.2 vs. 20.0 ± 20.6). All P values were ≤0.05. These data show evidence of delayed diagnosis and higher HS symptom burden amongst people from racial and ethnic minority groups, highlighting health disparities in HS.

Validation of TYK2 and exploration of PRSS36 as drug targets for psoriasis using Mendelian randomization

Psoriasis is a chronic inflammatory skin disorder with multiple causes, including genetic and environmental factors. Despite advances in treatment, there remains a need to identify novel therapeutic targets. A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets for psoriasis. Data on cis-expression quantitative trait loci were obtained from the eQTLGen Consortium (n = 31,684). Summary statistics for psoriasis (outcome) were sourced from the GWAS Catalog with a sample size of 484,598, including 5,427 cases and 479,171 controls. Colocalization analysis was used to assess whether psoriasis risk and gene expression were driven by shared single nucleotide polymorphisms. Drug prediction and molecular docking were utilized to validate the pharmacological value of the drug targets. The MR analysis found that 81 drug targets were significantly associated, and two (TYK2 and PRSS36) were supported by colocalization analysis (PP.H4 > 0.80). Phenome-wide association studies did not show any associations with other traits at the gene level. Biologically, these genes were closely related to immune function. Molecular docking revealed strong binding with drugs and proteins, as supported by available structural data. This study validated TYK2 as a drug target for psoriasis, in line with its existing clinical use, including the development of decucravacitinib. PRSS36 is a potential novel target requiring further investigation.

Synthesis of vitamin D3 loaded ethosomes gel to cure chronic immune-mediated inflammatory skin disease: physical characterization, in vitro and ex vivo studies

The purpose of the current work was to develop and characterize ethosomes of vitamin D3 gel that could more effectively work against psoriasis. Psoriasis is a chronic immune-mediated inflammatory skin disease. Due to vitamin D3 role in proliferation and maturation of keratinocytes, it has become an important local therapeutic option in the treatment of psoriasis. In this research we have initiated worked on ethosomes gels containing vitamin D3 to treat psoriasis. Soya lecithin 1–8% (w/v), propylene glycol and ethanol were used to create the formulations, which were then tested for vesicle size, shape, surface morphology, entrapment effectiveness, and in vitro drug permeation. The drug encapsulation efficiency of ethosomes was 96.25% ± 0.3. The particle sizes of the optimized ethosomes was 148 and 657 nm, and the PDI value was 0.770 ± 0.12 along with negative charge − 14 ± 3. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) along with thermogravimetric analysis (TGA) studies confirmed the absence of interactions between vitamin D3 and other ingredients. It was determined that the total amount of medication that penetrated the membrane was 95.34% ± 3. Percentage lysis was very negligible for all strengths which were found less than 15%. Based on our research, ethosomes appear to be safe for use. The vitamin D3 ethosomal gel order, description, pH, and viscosity were all within the specified ranges, according to the findings of a 6-month investigation into the stability profile of the completed system. In this research, we successfully prepared ethosomes loaded with vitamin D3 and then converted it into gel for patients’ easy applications.

Exploring the Neuropsychiatric Dimensions of Psoriasis: Pathophysiology, Clinical Implications, and Integrated Care Approaches

&lt;p&gt;&lt;span lang="RO"&gt;Psoriasis is a long-term inflammatory skin disorder that significantly affects a patient's quality of life in addition to having notable physical symptoms. Recent research has increasingly focused on the neuropsychiatric dimensions of psoriasis, recognizing the complex interplay between psychological health and dermatological disease. There is growing recognition of the correlation between psoriasis and neuropsychiatric conditions such as anxiety, depression, and cognitive decline, indicating the reciprocal interaction of the skin and brain. This study explores the prevalence and implications of neuropsychiatric disorders among 3,850 psoriasis patients, of whom 458 were diagnosed with neuropsychiatric conditions. The results emphasize the value of treating psoriasis with a multidisciplinary approach. Integrating care that addresses dermatological and neuropsychiatric health is crucial for improving patient outcomes and quality of life.&lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;em&gt;&lt;span lang="RO"&gt;&lt;br /&gt;&lt;/span&gt;&lt;/em&gt;&lt;/p&gt;

Factors Associated with Severe Hidradenitis Suppurativa, Using Hurley Staging and Metascore

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease for which certain risk factors are well known: obesity and smoking (in particular). However, the factors associated with more severe conditions, and therefore potential aggravators of the disease, remain a matter of debate. Our study aims to determine the clinical factors associated with severe HS using several severity scores. Methods: The data were obtained via the ERHS questionnaire from patients exclusively recruited at Erasme Hospital in Brussels. The severity of HS was firstly estimated by the Hurley score, and secondly by a metascore, a system combining the iHS4, HS-PGA, SAHS, and DLQI. Univariable and multivariable analyses were performed. Results: Six hundred and forty-seven patients were included in the Hurley analysis, and 456 patients in the metascore analysis. In multivariable analysis, men have a more severe metascore than women (odds ratio [OR] = 1.89, p = 0.022), smoking was associated with a more severe disease according to metascore, especially in mild cases (OR = 0.76, p = 0.043), and an elevated body mass index was associated with having Hurley stage III disease compared to Hurley I or II disease (OR = 1.09, p = 0.001). A significant association is also shown between blood pressure and Hurley stage (OR = 0.97, p = 0.025). Self-reports of nonsteroidal anti-inflammatory drugs aggravating the disease is also a factor associated with greater severity according to the metascore (OR = 0.12, p = 0.008). Finally, several locations of HS lesions were associated with greater severity, in particular the armpits according to the metascore (OR = 0.29, p < 0.001), and the perianal area according to the Hurley score (OR = 0.15, p < 0.001). Conclusion: HS seems to be more severe in men; smoking seems to aggravate mild cases of HS, while increased body mass index plays a major role in the transition from Hurley II to Hurley III.