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Baseline Th17/Tc17 and LAG-3 levels serve as candidate exploratory markers for early ixekizumab response in psoriasis
No abstract supplied.Weiterlesen
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Perceptions and Experiences of Patients Across All Skin Tones Living with Psoriasis in Canada.
IntroductionPsoriasis is a chronic inflammatory skin disease that significantly impacts patients' quality of life. Patients with skin of colour (SoC) often face unique barriers related to gaining access to care, diagnosis and treatment, which can contribute to health disparities. The aim of this study was to assess patient-reported experiences across the psoriasis care continuum in Canada, comparing white and non-white populations.MethodsA 15-min online survey was administered between 9 December and 19 December 2022 to patients ≥ 18 years with a confirmed psoriasis diagnosis. The survey included 33 questions covering demographics, medical history, psoriasis experience and access to information. Responses were analysed using t-tests at a 90% confidence level to identify significant differences based on ethnicity, treatment users, gender, psoriasis severity and region.ResultsOf approximately 2500 invited participants, 103 met the eligibility criteria: 62 self-identified as white and 41 as non-white. A higher proportion of non-white patients reported severe psoriasis, delays in diagnosis and greater emotional and social burden during the pre-diagnosis stage. Non-white patients were more frequently diagnosed and treated by dermatologists and more commonly used non-topical therapies. Misdiagnosis, often as eczema or dermatitis, was more prevalent among non-white patients. Treatment initiation was more commonly delayed in non-white patients, with 71% reporting difficulty accessing effective therapy, compared to 31% of white patients. A greater proportion of non-white respondents sought additional support and education, especially for mental wellness and advocacy resources.ConclusionDisparities in psoriasis care are evident across the experience of patients with psoriasis. Among those who participated in the survey, a greater proportion of the non-white patients faced delayed diagnosis, misdiagnosis, and greater barriers to treatment access, often reflecting more severe disease and unmet informational needs. These findings highlight the importance of culturally competent care and inclusive research to ensure equitable outcomes for all patients with psoriasis. Enhanced representation in clinical trials and targeted health interventions are essential to address these disparities.Weiterlesen
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Targeting TYK2 in Cutaneous Autoimmunity: Deucravacitinib-Induced Remission of Discoid Lupus and Psoriasis with Supportive Confocal Microscopy Findings.
IntroductionCutaneous lupus erythematosus (CLE), particularly discoid lupus erythematosus (DLE), is a chronic autoimmune condition driven in part by type I interferon signaling. No systemic therapies are specifically approved for CLE, and management is often extrapolated from systemic lupus erythematosus. Deucravacitinib, a selective oral tyrosine kinase 2 (TYK2) inhibitor targeting the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, has shown efficacy in psoriasis and emerging promise in lupus.Case reportWe describe a 29-year-old woman with biopsy-proven DLE refractory to prednisone and hydroxychloroquine who subsequently developed moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] 16). Initial treatment with ixekizumab improved psoriasis but failed to control DLE, and psoriatic lesions later relapsed. Therapy was switched to deucravacitinib 6 mg daily. After 9 weeks, marked improvement of both conditions was observed (PASI 0.2) with progressive regression of DLE lesions. By week 27, complete clinical remission of psoriasis (PASI 0) and full resolution of DLE lesions were achieved, confirmed by reflectance confocal microscopy.ConclusionThis case highlights the potential of deucravacitinib as an effective therapeutic option for refractory DLE, particularly in patients with concomitant psoriasis, supporting TYK2 inhibition as a promising targeted strategy in cutaneous autoimmunity.Weiterlesen
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Impact of Pediatric Psoriasis on Child and Caregiver Health-Related Quality of Life: A Systematic Review and Meta-Analysis.
BackgroundPediatric psoriasis is a chronic inflammatory skin disease that affects both physical and psychosocial well-being. The impact of the disease extends beyond the patient, significantly affecting caregivers' emotional and functional quality of life.ObjectivesThis systematic review and meta-analysis aimed to evaluate the health-related quality of life (HrQOL) burden of pediatric psoriasis on children and their caregivers. The study also sought to identify clinical and child-related factors associated with increased impairment in HrQOL.MethodsA systematic search of MEDLINE and Embase databases was conducted according to PRISMA guidelines. Studies included children under 18 years of age with a diagnosis of psoriasis and/or their caregivers, reporting outcomes using validated HrQOL measures. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Where appropriate, correlation coefficients were pooled using random-effects meta-analysis after Fisher's Z-transformation.ResultsTwenty-one studies were included, encompassing 1038 children and 1161 caregivers. The most commonly used instruments were the Children's Dermatology Life Quality Index (CDLQI) and Family Dermatology Life Quality Index (FDLQI). Across studies, 84.8% of children and 96.1% of caregivers experienced some degree of HrQOL impairment. Meta-analysis revealed a moderate positive correlation between child disease severity (PASI scores) and caregiver HrQOL burden (r = 0.463), while no significant correlation was found with child age or disease duration. Amongst children, HrQOL was most affected in the domains of symptoms, leisure, and treatment-related concerns.ConclusionsPediatric psoriasis exerts a substantial impact on both child and caregiver quality of life, with greater burden associated with more severe disease. These findings highlight the need for early intervention and psychosocial support targeting families. Clinicians should consider the broader family context when managing pediatric psoriasis and prioritize counseling during disease flares to mitigate emotional and functional strain.Weiterlesen
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Alox8 knockout exacerbates imiquimod-induced psoriasis-like inflammation.
Lipoxygenases peroxidise polyunsaturated fatty acids, resulting in oxylipins, which may act pro- or anti-inflammatory. Arachidonate 15-lipoxygenase type B was shown to play a role in the resolution of keratinocyte inflammation and is upregulated in psoriasis. Its murine ortholog, arachidonate 8-lipoxygenase (Alox8), differs in regiospecificity in that it adds molecular oxygen to the 8th and not 15th carbon of arachidonic acid. This study aimed to determine if Alox8 plays a role in the resolution of murine imiquimod-induced psoriasis. Alox8 knockout (KO) mice, which are not commercially available, were generated with a functional KO targeting the enzyme's active site. Untargeted Lipidomics revealed changes in the skin lipidome from both imiquimod-induced psoriasis as well as between wild-type and KO mice. Furthermore, LC-MS/MS revealed a functional KO with reductions in Alox8-specific oxylipins. Lipid peroxidation marker 4-hydroxynonenal was elevated in the epidermis of wild-type mice from imiquimod treatment, however, it was significantly reduced in Alox8 KO mice. Alox8 KO mice exhibited a thickened epidermis, resulting from reduced DNA damage and increased proliferation. Moreover, immune cell infiltration was enhanced in Alox8 KO mice, including a higher abundance of γδ T cells. Elevated cytokine levels of interleukin-17 and -22, accompanied by keratinocyte-produced C-X-C motif chemokine ligand 1, were detected in the skin of Alox8 KO mice. Additionally, cyclooxygenase 2 expression and prostaglandin E2 levels were enhanced in Alox8 KO mice. These data demonstrate an exacerbated and prolonged inflammatory psoriasis phenotype in Alox8 KO mice, implying that Alox8 aids in the resolution of murine psoriasis.Weiterlesen
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Dimethyl fumarate attenuates subcutaneous adipose tissue inflammation in psoriasis.
Psoriasis is a chronic immune-mediated inflammatory disease with systemic manifestations beyond the skin, yet the role of subcutaneous adipose tissue (SAT) in disease biology and therapeutic response remains poorly understood. Here, we investigated inflammatory features of SAT in psoriasis and the effects of dimethyl fumarate (DMF) on this compartment. Six adults with moderate-to-severe plaque psoriasis received oral DMF for 24 weeks and were clinically evaluated measuring the Psoriasis Area and Severity Index (PASI), showing a consistent reduction in disease severity during treatment. Publicly available spatial transcriptomic data were analysed to profile inflammatory signatures in SAT clusters of psoriatic versus healthy skin. Bulk RNA sequencing was performed on SAT biopsies obtained from psoriatic plaques before and after DMF treatment in four patients. Complementary in vitro models using murine 3T3-L1 adipocytes and human adipocytes differentiated from mesenchymal stem cells were exposed to pro-inflammatory cytokines or macrophage-conditioned media (CM) with or without DMF to assess effects on inflammatory gene expression and NF-κB signalling. Spatial transcriptomics identified enrichment of inflammation-related pathways in SAT beneath psoriatic lesions. DMF treatment was associated with reduced expression of inflammatory mediators and with a shift in SAT transcriptional profile toward patterns observed in healthy tissue. In vitro, DMF significantly attenuated cytokine- and CM-induced adipocyte activation and reduced NF-κB phosphorylation in both murine and human adipocyte models. These data provide integrated clinical and experimental evidence that DMF treatment is associated with reduced disease activity and attenuation of inflammatory signalling within psoriatic SAT, supporting adipose tissue as a potentially modifiable inflammatory compartment in psoriasis.Weiterlesen
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Effects of biologics and small-molecule inhibitors on lipid profiles in patients with psoriasis or psoriatic arthritis: An analysis of current evidence.
ImportanceAvailable evidence reveals markedly divergent metabolic signatures across biologics and small-molecule inhibitors, highlighting the need for further investigations.ObjectiveTo address this knowledge gap, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in patients with psoriasis or psoriatic arthritis (PsA) to quantify the short- and long-term effects of targeted therapies on lipid profiles.Evidence reviewPubMed, Embase, and Cochrane databases were searched for RCTs and observational studies published through July 25, 2025. Eligible randomized RCTs were evaluated using the Cochrane Risk of Bias tool, while nonrandomized studies were assessed using the Methodological Index for Non-Randomized Studies. All lipid effect estimates were derived from within-group pre-to-post changes in patients with psoriasis or PsA.FindingsThirty-six articles involving 21,477 patients with psoriasis and 3098 patients with PsA (total 24,575) across seven targets were analyzed. The long-term use of Janus kinase inhibitors (JAKi) significantly increases total cholesterol (TC; weighted mean difference [WMD] = 7.03; 95% confidence interval [CI] = 1.22, 12.84), triglyceride (TG; WMD = 19.98; 95% CI = 13.82, 26.14), high-density lipoprotein cholesterol (HDL-c; WMD = 6.87; 95% CI = 4.38, 9.36), and low-density lipoprotein cholesterol (LDL-c; WMD = 12.37; 95% CI = 7.24, 17.50) levels. Long-term tumor necrosis factor alpha inhibitors (TNFi) significantly lowers TC (WMD = -8.40; 95% CI = -15.21, -1.60), TG (WMD = -15.22; 95% CI = -21.92, -8.51), and LDL-c (WMD = -10.61; 95% CI = -16.77, -4.45) levels while raising HDL-c (WMD = 4.13; 95% CI = 1.23; 7.03) levels. Long-term interleukin-17 A inhibitors significantly increases TG (WMD = 7.31; 95% CI = 3.17, 11.46) levels, whereas IL-23p19 inhibitors yield the opposite effect (WMD = -32.08; 95% CI = -51.87, -12.30).Conclusions and relevanceOur data underscore the need for routine lipid monitoring during TNF-α- and JAK-targeted therapy in patients with psoriasis or PsA. Due to the limitations of our analysis, well-designed prospective trials with extended follow-up periods are warranted to validate and refine these observations.Weiterlesen
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Der Alox8-Knockout verschlimmert die durch Imiquimod hervorgerufene psoriasisähnliche Entzündung.
Originaltitel: Alox8 knockout exacerbates imiquimod-induced psoriasis-like inflammation. Link zur Quelle
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Schmerzempfinden, Müdigkeit und Schlafqualität zu Beginn der Behandlung sagen eine Schmerzverbesserung nach 12 Wochen bei entzündlicher Arthritis voraus: Retrospektive Real-World-Analyse einer Kohorte von Nutzern einer digitalen Gesundheitsanwendung.
# Neuer Blick auf Schmerzvorhersage: Was Schlaf und Müdigkeit über deine Zukunft verraten Das Abstract dieser Studie ist leider nicht verfügbar. Aber der Titel verrät bereits viel Spannendes: Forscher haben analysiert, wie dein Ausgangsschmerz, deine Müdigkeit und deine Schlafqualität vorhersagen, ob sich dein Schmerz in den nächsten 12 Wochen verbessert. Das ist wichtig für Menschen mit entzündlichen Erkrankungen wie Psoriasis-Arthritis. Denn aktuelle Forschung zeigt einen starken Zusammenhang: Schlafprobleme verstärken die Schmerzempfindlichkeit.[1][4] Gleichzeitig beeinflussen Müdigkeit und Schmerz sich gegenseitig.[7] Die Studie nutzte dabei echte Patientendaten aus einer Gesundheits-App. Das ist ein großer Vorteil gegenüber klassischen Studien. So erfahren Ärzte, wie Menschen wirklich leben und welche Faktoren tatsächlich zählen. **Das Fazit für dich:** Wenn du verstehst, welche Ausgangsfaktoren deine Schmerz-Besserung beeinflussen, kannst du gezielter ansetzen. Besserer Schlaf und weniger Müdigkeit könnten der Schlüssel sein. Originaltitel: Baseline pain, fatigue, and sleep quality predict 12-week pain improvement in inflammatory arthritis: retrospective real-world analysis of a digital health application cohort. Link zur Quelle
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Palmoplantar pustulosis: pathogenesis, differential diagnosis, and treatment.
Palmoplantar pustulosis (PPP) is a chronic inflammatory and often painful disease characterized by sterile pustules on the palms and soles, significantly impairing quality of life. Women are more frequently affected than men, and smoking is a major trigger. Under biologic therapies, especially TNF antagonists, a paradoxical PPP may occur. PPP is associated with psoriasis vulgaris and may be accompanied by osteoarticular involvement. Pathogenetically, PPP likely begins around the acrosyringium, with the pustules consisting almost exclusively of infiltrating neutrophilic granulocytes attracted by chemotactic factors secreted by activated keratinocytes. Inflammation is sustained through a self-amplifying cytokine network, including interleukin (IL)-17, IL-19, and related mediators. Treatment options for PPP include topical treatments, UV-phototherapies - particularly topical PUVA (Psoralen plus UVA) therapy- and systemic therapies. Systemic agents comprise conventional treatments such as acitretin, methotrexate, fumaric acid esters, and ciclosporin, newer small molecules like apremilast and Janus kinase inhibitors, as well as biologics. Conventional systemic therapies are often not sufficiently effective in PPP and associated with side effects. Currently, among systemic therapies, only acitretin is approved for PPP. In recent years, placebo-controlled studies have demonstrated a significant effect of apremilast, brodalumab, guselkumab and risankizumab on PPP, and further studies with topical and systemic Janus kinase inhibitors as well as IL-17A/F inhibitors are underway.Weiterlesen
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Palmoplantare Pustulose: Entstehung, Differentialdiagnose und Therapie
No abstract supplied.Weiterlesen
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Should TNF inhibitors be avoided in psoriasis patients with latent tuberculosis?
No abstract supplied.Weiterlesen
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The role of inflammatory cell death in type 1 dominant inflammatory skin diseases.
While there has been significant progress in the development of new therapies for psoriasis and atopic dermatitis in recent years, innovation in the field of type 1 dominant skin diseases is still limited. This category comprises diseases characterized by a cytotoxic immune reaction directed against resident skin cells. The histological correlate is interface dermatitis, defined by a subepidermal inflammatory infiltrate associated with epidermal keratinocyte apoptosis. Representative conditions include lichen planus, cutaneous lupus erythematosus, erythema multiforme, alopecia areata, and vitiligo. Immunologically, there is a dominance of Th1 cells, which mediate their effects through interferon-γ and tumor necrosis factor-α. Recent findings have shown that, in addition to apoptosis, other forms of cell death are also activated by this immune response, such as necroptosis. In contrast to apoptosis, necroptosis represents a strong immunological stimulus and thus further intensifies the local inflammatory response. These findings open new therapeutic perspectives, as numerous necroptosis inhibitors are currently under investigation for various inflammatory diseases. The present review summarizes the immunopathogenesis of type 1-dominant skin diseases and highlights emerging therapeutic strategies, including the inhibition of inflammatory cell death.Weiterlesen
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Evidenz‐ und konsensbasierte (S3) Leitlinie: Lichen sclerosus
No abstract supplied.Weiterlesen
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Evidence- and consensus-based guideline on lichen sclerosus.
The German-language, consensus- and evidence-based S3 guideline on lichen sclerosus (LS) was developed based on the European "EuroGuiDerm Guideline on lichen sclerosus" under the leadership of the German Dermatological Society (DDG) and the German Society for Gynecology and Obstetrics (DGGG). Particular emphasis was placed on adapting the recommendations to the healthcare conditions in German-speaking countries. The interdisciplinary guideline development group consisted of 24 experts from 16 medical societies and actively included patient representatives in the development process. The guideline provides comprehensive recommendations on diagnosis, patient management, follow-up care, and patient education, as well as the treatment of both genital and extragenital LS in women, men, girls, and boys. Regardless of age or sex, ultrapotent or potent topical glucocorticosteroids in combination with emollients remain the standard therapy for genital LS. In male patients with LS-associated phimosis who do not respond sufficiently to standard therapy, circumcision with complete removal of the foreskin is indicated. For extragenital LS, phototherapy with UV light is recommended as an adjunct to topical treatment. Topical calcineurin inhibitors are second-line therapy.Weiterlesen
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TYMP upregulation mediated by the hyperactivated IL-17/NF-κB1 axis promotes psoriasis through enhancing aberrant keratinization and neutrophil-mediated inflammation.
No abstract supplied.Weiterlesen
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Development and validation of a prediction model for primary non-response to IL-17A inhibitors in psoriasis
No abstract supplied.Weiterlesen
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Increased Serum Cold-Inducible RNA-Binding Protein Levels in Psoriasis.
BackgroundPsoriasis is a chronic inflammatory skin disorder typified by well-demarcated erythematous plaques with scales. While considered an immune-driven condition, its underlying molecular triggers remain insufficiently defined. Cold-inducible RNA-binding protein (CIRP), a stress-response protein, has recently been recognized as a damage-associated molecular pattern that can stimulate immune responses.ObjectiveThis study aimed to explore the potential association between circulating CIRP levels and the clinical as well as histological characteristics of psoriasis.MethodsSerum CIRP concentrations were analyzed in 67 individuals diagnosed with psoriasis and 20 healthy controls. Relationships between CIRP expression and various clinical and histological indices were also examined.ResultsPatients with psoriasis exhibited significantly elevated serum CIRP levels compared to healthy individuals. Although correlations were observed between CIRP and certain clinical and histological indicators, CIRP levels did not significantly differ based on disease severity (Psoriasis Area and Severity Index score), joint involvement, or nail changes.ConclusionOur findings support the notion that CIRP may be involved in the immunopathogenesis of psoriasis and could be considered a prospective target for therapeutic modulation.Weiterlesen
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Janus Kinase Inhibitors for Treatment of Palmoplantar Pustulosis, Generalized Pustular Psoriasis, and Palmoplantar Pustular Psoriasis: A Systematic Review of the Literature.
IntroductionPalmoplantar pustulosis (PPP) is a chronic, recurrent, inflammatory disease and assumed to be a subtype of psoriasis. Pustular psoriasis (PP) is a chronic inflammatory disease that is further subclassified into various entities with different presentations including generalized pustular psoriasis (GPP) and palmoplantar pustular psoriasis (PPPP). Given the central role of the JAK-STAT pathway in cytokine signaling, this systematic review evaluated the effectiveness and safety of Janus kinase inhibitors (JAK-I) in these PP subtypes.MethodsFollowing PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Scopus, Web of Science, and Embase up to November 13, 2025. Eligible studies included assessing JAK-I in PPP, GPP, or PPPP. Exclusion criteria were reviews, articles without full-text, SAPHO syndrome, and animal/in vitro studies. Risk of bias was assessed using the NHLBI quality assessment tool for clinical studies and Murad et al.'s checklist for case reports/series.ResultsThirty-seven studies were included (29 case reports, 4 case series, and 4 clinical studies), encompassing 157 patients (60.5% female; mean age 46.8 years). Treatments involved tofacitinib, upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib. In PPP, pooled meta-analysis demonstrated a PPPASI-50 response rate of 85.5% (95% CI, 71.3-93.3), with upadacitinib achieving 90.9% (95% CI, 81.7-95.7). Case reports and series showed 88.1% clearance or near-clearance within a mean of 2.5 months. GPP patients (n = 5) achieved rapid clearance or marked improvement within 2-12 weeks. Adverse events (18.7%) were generally mild, most commonly acneiform eruptions, headache, and transient liver enzyme elevations, with no severe events reported.ConclusionJAK-I demonstrate high response rates and rapid improvement with manageable safety profiles. However, the current evidence is limited by small sample sizes, short follow-up durations, and reliance on case-based data. They represent a promising therapeutic option and warrant further evaluation in larger controlled studies to establish long-term efficacy and safety.Weiterlesen
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Application of Trichoscopy and Novel Non-Invasive Imaging Techniques in the Diagnosis and Management of Patients with Scalp Psoriasis.
Scalp psoriasis affects up to 80% of patients with psoriasis and possesses a significant challenge as a difficult-to-treat area. A comprehensive literature search was conducted in PubMed using relevant keywords to identify recent studies focusing on scalp psoriasis diagnosis and treatment. The diagnosis is mainly based on clinical evaluation and trichoscopy. Other diagnostic tools, such as histopathology, optical coherence tomography, reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT) may offer valuable insights in doubtful cases. Topical therapies (glucocorticosteroids, a betamethasone-calcipotriol combination or calcineurin inhibitors) remain the first-line therapy for mild to moderate cases. Patients with severe scalp psoriasis and those who do not respond to topical treatment are candidates for systemic therapy, including targeted therapy (interleukin-17 inhibitors, interleukin-23 inhibitors, tumor necrosis alpha inhibitors) or classic treatment (methotrexate, cyclosporine) Recent studies have demonstrated promising outcomes with novel treatments including Janus kinase (JAK) inhibitors and other new small molecules. This review provides updated information focused on diagnostic methods and targeted treatment of scalp psoriasis with relevance to clinical management of patients.Weiterlesen
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Association of <i>PTPN22</i> and <i>NLRP3</i> Gene Polymorphisms with Psoriasis Susceptibility in a Han Chinese Population.
ObjectiveTo investigate the associations among protein tyrosine phosphatase (PTPN22), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and genetic susceptibility to psoriasis in the Jiujiang population.MethodsA total of 120 psoriasis patients and 90 healthy controls were enrolled. Polymerase chain reaction-based sequencing was performed to determine the distribution of PTPN22 rs1310182, rs2488457, and NLRP3 rs10754558 genotypes. Logistic regression analysis was conducted to evaluate the associations between the genotypes, alleles, and genetic models of these three loci and psoriasis susceptibility. The associations between these polymorphisms and disease subtypes or severity were also explored.ResultsWith respect to the PTPN22 rs2488457 locus, the GG genotype and G allele were identified as risk factors for psoriasis susceptibility (p = 0.026 and p = 0.004, respectively). In the dominant model, carriers of the GG genotype exhibited a significantly higher risk of psoriasis than did those with the GC+CC genotype (p = 0.016). No significant associations were observed between the rs1310182 or rs10754558 polymorphisms and psoriasis susceptibility (p > 0.05). In addition, none of the three loci were significantly correlated with the disease subtype or severity (p > 0.05).ConclusionsIn the Jiujiang population, the GG genotype and G allele of the PTPN22 rs2488457 locus may be key factors influencing psoriasis susceptibility.Weiterlesen
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Core Differentially Expressed Genes in Psoriasis Lesions: An Integrated Analysis of Four GEO Datasets.
PurposePsoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation, affecting approximately 2% of the global population.Patients and methodsThis study explored the role of specific molecular biomarkers in the pathogenesis of psoriasis through integrative bioinformatics analysis, aiming to improve diagnostic precision and uncover therapeutic targets. Four independent transcriptomic datasets (GSE34248, GSE41662, GSE50790, and GSE6710) were analyzed using bioinformatics tools to identify consistently dysregulated genes in psoriatic lesions. Subsequently, we constructed a protein-protein interaction (PPI) network using the STRING database and analyzed key gene modules and hub genes involved in disease pathways.ResultsThis integrative approach led to the identification of 32 genes consistently dysregulated across all four datasets. Pathway enrichment highlighted significant involvement in biological processes such as keratinization (p = 1.53 × 10-6) and cornified envelope formation (p = 1.93 × 10-5), which are central to the epidermal alterations observed in psoriasis. Several gene families implicated in skin homeostasis and inflammatory regulation were found to contribute to psoriasis pathogenesis.ConclusionThese findings underscore the relevance of these core genes and pathways in the molecular landscape of psoriasis and offer potential targets for future functional validation and therapeutic intervention.Weiterlesen
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Albendazole-loaded chitosan nanoparticle conjugated with hyaluronic acid for the treatment of psoriasis.
ObjectiveTo design and develop hyaluronic acid (HA) conjugated Albendazole (ABZ) loaded chitosan nanoparticles (HA-ABZ-CSNP) loaded hydrogel for the treatment of psoriasis.SignificanceAlbendazole (ABZ), a commonly used anti-parasitic drug, has garnered a lot of attention lately including anticancer and anti-psoriasis properties. Chitosan nanoparticle followed by conjugation with HA was formulated in hydrogel base making it an excellent strategy for targeting overexpressed CD44 receptor on psoriatic skin as well as alleviating the problems, such as dryness, itchiness associated with psoriasis.MethodsABZ-CSNP was formulated by ionic gelation technique followed by conjugation with hyaluronic acid (HA) and was evaluated for particle size, zeta potential, entrapment efficiency, respectively. Developed HA-ABZ-CSNP were incorporated into hydrogel base and were evaluated for in-vitro drug release. Ex-vivo studies were performed. In-vivo studies were performed on Balb/c mice and tests, such as Psoriasis Area Severity Index (PASI), Spleen weight assessment, and histopathological studies were conducted.ResultsOptimized HA-ABZ-CSNP showed a particle size of 170.1 ± 76.38 nm, zeta potential of 31.6 mV, and entrapment efficiency of 98.89%, respectively. Developed HA-ABZ-CSNP hydrogel showed a Korsemeyer and Peppas release model and an in-vitro release of 93.90 ± 32.50 % in around 24 h. Ex-vivo studies were conducted which showed 30.74 ± 13.65% in 24 h. In-vivo studies conducted on Balb/c mice showed reduced PASI, Spleen weight as well as reduced keratinocyte proliferation in histopathological studies.ConclusionsIn conclusion, developed novel formulation of ABZ reduced keratinocyte proliferation making it a possible effective strategy in the management of psoriasis.Weiterlesen
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Comparative Study Assessing Multiple Switches Between Biosimilar ABP 501 (adalimumab-atto) and Adalimumab Reference Product in Patients with Plaque Psoriasis.
IntroductionABP 501, now approved as AMJEVITA® (adalimumab-atto, USA)/AMGEVITA® (adalimumab, EU), is a biosimilar to adalimumab reference product (RP, Humira®) indicated for the treatment of various chronic inflammatory conditions. This multicenter, randomized, double-blind study aimed to investigate the impact of multiple switches between adalimumab RP and ABP 501 as compared with continued-use of adalimumab RP.MethodsThis study (NCT05073315) consisted of a 12-week lead-in period where adults with moderate-to-severe plaque psoriasis received adalimumab RP subcutaneously every 2 weeks (Q2W), followed by a double-blind, two-parallel arm period in which patients were randomized to either the continued-use group (adalimumab RP Q2W, weeks 12-28) or switching group (ABP 501, weeks 12 and 14; adalimumab RP, weeks 16 and 18; ABP 501 Q2W, weeks 20-28). The primary pharmacokinetic (PK) endpoints were area under the serum concentration-time curve (AUCtau) and maximum observed serum concentration (Cmax) between weeks 28 and 30. Secondary endpoints included additional PK assessments and measures of safety, immunogenicity, and efficacy.ResultsA total of 425 patients were enrolled across 85 centers. Adherence to dosing protocol and completion/discontinuation rates were similar between groups. The ratio of geometric least squares means (90% confidence interval; CI) between the continued-use group and switching group for AUCtau was 1.0516 (0.9010, 1.2273) and for Cmax was 1.0044 (0.8717, 1.1574); 90% CIs were contained within the prespecified similarity margin (0.8, 1.25). Secondary endpoints were comparable between groups. There were no new or concerning safety signals.ConclusionThis study demonstrates PK similarity in patients with plaque psoriasis who underwent three treatment switches between adalimumab RP and ABP 501 as compared with those who received continuous treatment with adalimumab RP. Safety, immunogenicity, and efficacy profiles were comparable. Overall, results support the interchangeability designation of ABP 501 with adalimumab RP, consistent with the US Food and Drug Administration (2019) guidelines.Trial registrationThis study was registered as NCT05073315.Weiterlesen
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The Impact of Targeted Therapies on the Bone-Vascular Axis in Psoriasis: A Narrative Review.
This narrative review elucidates the impact of biologics and small-molecule inhibitors on bone metabolism and cardiovascular risk in patients with psoriasis. Psoriasis is a systemic immune-mediated disorder characterized by a "Calcification Paradox"-the simultaneous occurrence of skeletal bone loss and vascular calcification. We explore the molecular mechanisms of the "Bone-Vascular Axis", highlighting how the IL-23/IL-17 axis disrupts the RANKL/OPG balance and drives the osteogenic transdifferentiation of vascular smooth muscle cells. We critically evaluate the therapeutic impact of targeted agents, noting that IL-23 and dual IL-17A/F inhibitors offer significant structural protection in psoriatic arthritis. Regarding oral therapies, while JAK inhibitors necessitate cardiovascular risk stratification, the novel TYK2 inhibitor deucravacitinib demonstrates a favorable cardiovascular safety profile based on long-term extension data, although large-scale, hard endpoint-driven cardiovascular outcome trials (CVOTs) remain necessary to confirm definitive long-term protection. We conclude that effective management must shift from skin-focused control to a comprehensive systemic strategy targeting the bone-vascular axis to mitigate long-term comorbidities.Weiterlesen