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Stress in den ersten Lebensjahren, vor allem durch Veränderungen in der Familie wie Trennung, Scheidung oder neue Geschwister, kann das Risiko für Psoriasis später deutlich erhöhen[1][2][3][5]. Besonders Kinder, die im ersten Lebensjahr so einen Umbruch erleben, haben etwa ein drei- bis vierfach höheres Risiko als andere[2][3][5]. Die Forschenden erklären das damit, dass kleine Kinder auf Stress besonders sensibel reagieren. Ihr Körper schüttet dann mehr Stresshormone wie Cortisol aus, was das Immunsystem beeinflusst und die Entstehung von Autoimmunerkrankungen wie Psoriasis begünstigen kann[2][5]. Die Ergebnisse stammen aus einer großen schwedischen Studie. Auch wenn die Daten überwiegend aus Schweden kommen, zeigt die Studie: Ein sicheres und stabiles Umfeld ist für die gesunde Entwicklung der Kinderhaut sehr wichtig[2][5]. Originaltitel: Early childhood stress and the risk of developing psoriasis: a cohort study. Link zur Quelle

Forscher haben ein wichtiges Protein entdeckt, das eine spezielle Form von Psoriasis antreibt: SERPINB3. Dieses Protein spielt eine zentrale Rolle bei der "ekzematisierten Psoriasis", einer Unterform der Schuppenflechte. Bei dieser besonderen Variante reagiert das Immunsystem auf körpereigene Strukturen. Die Forscher fanden heraus, dass SERPINB3 besonders stark in den betroffenen Hautstellen vorkommt. Hautzellen produzieren dieses Protein vermehrt, wenn zwei verschiedene Entzündungssignale zusammenwirken. Im Tierversuch verstärkte das Protein die Entzündung und veränderte die Immunantwort. Bei Menschen mit ekzematisierter Psoriasis vermehrten sich die T-Zellen der Haut als Reaktion auf SERPINB3. Diese Reaktion trat weder bei klassischer Plaque-Psoriasis noch bei reinem Ekzem auf. SERPINB3 gehört zu einer Proteinfamilie, die bereits mit Autoimmunreaktionen bei Psoriasis in Verbindung gebracht wurde[1][2]. Aus SERPINB3 kann durch Spaltung das Protein Pso p27 entstehen, das Entzündungen verstärkt[2]. Diese Entdeckung könnte helfen, verschiedene Psoriasis-Formen besser zu unterscheiden und gezielter zu behandeln. Sie zeigt, dass ekzematisierte Psoriasis eine eigenständige Form mit besonderen Merkmalen ist. Originaltitel: Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis. Link zur Quelle

Die Behandlung von **Psoriasis-Arthritis** hat sich in den letzten Jahren stark verbessert[2][3]. Heute gibt es viele neue Medikamente, die gezielt gegen Entzündungen wirken und die Beschwerden lindern[3][4]. Biologika, also spezielle Eiweiß-Medikamente, gelten jetzt oft als erste Wahl, wenn du noch keine Therapie hattest[1][5]. Manche dieser Mittel sind Spritzen, andere sind Tabletten[3][4]. Weil Psoriasis-Arthritis oft mit anderen Krankheiten wie Herzproblemen oder Diabetes zusammen auftritt, achten Ärzte jetzt mehr auf begleitende Beschwerden[2]. Die Forschung sucht weiter nach Mitteln, die noch besser helfen und dabei weniger Nebenwirkungen haben[4]. Für dich bedeutet das, dass die Chancen steigen, ein Medikament zu finden, das zu deinem Alltag passt und deine Lebensqualität verbessert[1]. Am Welt-Psoriasis-Tag 2025 steht vor allem im Fokus, wie wichtig eine gute Rundum-Behandlung ist. Auch wenn schon viel erreicht wurde, gibt es noch offene Fragen zu den Ursachen der Krankheit. Darum bleibt die Suche nach neuen Therapien wichtig[2][6]. Originaltitel: Psoriatic arthritis: strategy shaping treatment Link zur Quelle

Golimumab zusammen mit Methotrexat und Kortison hilft bei früher, unbehandelter Psoriasis-Arthritis nicht besser als nur Methotrexat und Kortison. Beide Gruppen hatten nach 24 Wochen ähnliche Verbesserungen beim Krankheitsverlauf. Allerdings mussten Patienten ohne Golimumab öfter zusätzliches Kortison bekommen. Nach einem Jahr waren die Ergebnisse in beiden Gruppen weiterhin stabil. Es traten keine schweren oder überraschenden Nebenwirkungen auf[4]. Originaltitel: Effect of a treatment strategy utilising golimumab, methotrexate and corticosteroids versus methotrexate and corticosteroids in early, untreated psoriatic arthritis (GOLMePsA): a single-centre, double-blind, parallel-group, randomised controlled trial Link zur Quelle

Many biologic therapies are available for moderate-to-severe plaque psoriasis. A systematic literature review and network meta-analysis (NMA) was conducted to compare the efficacy of the interleukin (IL)-23 inhibitor, tildrakizumab, with other biologics at up to 28 weeks of treatment. The literature search was conducted on January 22, 2024, searching MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) investigating the comparative efficacy and safety of biologics in adult Asian patients with moderate-to-severe plaque psoriasis. NMAs were conducted for ≥ 75%, ≥ 90%, and 100% reduction in Psoriasis Area and Severity Index score (PASI 75, 90, and 100) and achieving a Physician Global Assessment (PGA) score of 0 or 1 after the induction period (12 and 16 weeks) and mid-term (28 weeks) follow-up. NMAs were conducted using the Bayesian framework outlined in the National Institute of Clinical Excellence guidelines. Nineteen RCTs conducted in China, Japan, Korea, and Taiwan with 11 different biologics were included. At Week 12, tildrakizumab had lower efficacy compared to other biologics. Between Weeks 12 and 28, the proportion of patients achieving PASI 75/90/100 with tildrakizumab increased from 60.77% to 81.84%, from 38.54% to 71.23%, and from 6.97% to 22.64%, respectively. At Week 28, tildrakizumab efficacy was comparable to other biologic therapies studied here, including tumor necrosis factor-alpha (TNFα), IL-17, IL-12/IL-23, and other IL-23 inhibitors. The efficacy of tildrakizumab improved over time, which underscores the importance of evaluating the sustained efficacy of tildrakizumab over the long term. Combined with low dosing frequency, tildrakizumab offers an effective treatment option for patients with moderate-to-severe plaque psoriasis.Weiterlesen

No abstract supplied.Weiterlesen

BackgroundPsoriasis is a chronic immune-mediated inflammatory disease. Systemic therapy is usually applicable to patients who have failed topical treatment or phototherapy, but the value of early systemic therapy remains unclear.PurposeThis study aimed to evaluate the impact of disease duration on the clinical efficacy and patients reported outcomes in moderate to severe psoriasis patients treated with systemic agents.MethodsOur research was based on the SPEECH, an observational, prospective, multicenter registry. Adult patients with moderate to severe psoriasis receiving systemic therapy (including biologics, methotrexate or acitretin) were divided into groups based on disease duration: <2 years, 2~10 years, and ≥10 years. The clinical efficacy was assessed using PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), PGA (Physician Global Assessment). The Dermatology Life Quality Index (DLQI), PtGA (Patient Global Assessment) and the Hospital Anxiety and Depression Scale (HADS) were used to assess the patients reported outcomes. The treatment outcomes were analyzed at 3 months and 6 months. Using multiple logistic regression to analyze the differences between patients with different disease duration, and conducting subgroup analysis and sensitivity analysis to test the robustness of the research results.ResultsA total of 1908 patients who met the criteria were included in the analysis. After 3 months of treatment, the PASI75 response rates for the three groups of patients (<2 years, 2-10 years, and ≥10 years) were 55%, 55% and 60%, respectively all p value >0.05. No significant differences were observed among the three groups in the rates of achieving BSA <1/3, PGA 0/1, DLQI 0/1, PtGA 0/1, HADS-A = 0, and HADS-D = 0. Notably, these outcomes still showed no significant differences at 6 months. Subgroup and sensitivity analyses also yielded consistent results.ConclusionDisease duration does not significantly affect clinical efficacy or patients reported outcomes in patients with moderate-to-severe psoriasis receiving systemic therapy. These results indicate that early systemic therapy does not improve treatment outcomes in real clinical settings, thereby supporting the continued efficacy of step-up treatment strategy and providing novel insights into clinical practice management.Weiterlesen

PurposeSecukinumab, an interleukin-17 A (IL-17 A) inhibitor, is an approved treatment for psoriasis, but effects on the hypothalamic pituitary adrenal (HPA) axis are unknown.MethodsIn a 16-week randomized controlled trial, 105 patients with psoriasis received secukinumab at either 300 or 75 mg. Plasma levels of IL-17 A, cortisol, adrenocorticotropic hormone, prolactin, dehydroepiandrosterone and perceived stress using Perceived Stress Scale (PSS-10) were measured at baseline and every four weeks. Treatment response was assessed using Psoriasis Area and Severity Index (PASI).ResultsBoth dosage groups showed significant increases in IL-17 A and cortisol, with no differences between groups. Cortisol increased by approximately 33 %, indicating activation of HPA axis. Changes in cortisol did not correlate with PASI. PSS-10 inversely correlated with cortisol at baseline, and shifted positive during follow-up.ConclusionSecukinumab treatment in psoriasis is accompanied by HPA axis activation. Further studies are needed to determine the duration, mechanisms, and magnitude of this activation.Weiterlesen

Several clinical trials on repurposing of roflumilast are in progress, majorly focused on the potential treatment for psoriasis and atopic dermatitis like inflammatory skin diseases. Therefore, the current research focuses on formulation and in vivo evaluation of repurposed drug roflumilast loaded nanoemulgel for topical management of psoriasis. The roflumilast loaded nanoemulsion was prepared by spontaneous nanoemulsification method. The optimized roflumilast nanoemulsion has shown droplet size of found to be 10.92 ± 0.15 nm, PDI < 0.3. The optimized nanoemulsion was further converted into gel referred as nanoemulgel. The prepared nanoemulgel has shown pseudoplastic shear thinning behaviour with pH value ranging between the skin pH while the content of roflumilast (%) was found >95%. Ex vivo permeation study of roflumilast nanoemulgel showed significantly higher skin retention of roflumilast (**p < 0.01) compared to free roflumilast gel. The antipsoriatic potential of roflumilast nanomulgel has been evaluated in psoriasis model of BALB/c mice. The levels of pro-inflammatory cytokines including IL-17, IL-22, IL-23 and TNF-α in skin homogenates of mice group treated with roflumilast nanoemulgel showed significant reduction compared to negative control. Furthermore, the histopathology of mice skin treated with topical roflumilast nanoemulgel showed reduced psoriatic lesions. The study findings clearly demonstrated the effectiveness roflumilast loaded nanoemulgel (0.1% w/w) for the topical management of psoriasis in mice.Weiterlesen

Secukinumab ist ein Medikament gegen Psoriasis, das gezielt IL-17A hemmt. Ein aktueller Test mit 105 Patienten zeigt: Wer Secukinumab bekommt, hat nach 16 Wochen deutlich mehr Cortisol im Blut, etwa ein Drittel mehr als vor der Therapie. Das bedeutet, die körpereigene Stressachse, die HPA-Achse, wird aktiviert. Interessant ist, dass die Cortisoländerungen nicht direkt mit dem Schweregrad der Schuppenflechte zusammenhängen. Die wahrgenommene Stressbelastung hat zu Beginn wenig mit dem Cortisolwert zu tun, später jedoch einen Zusammenhang. Ob und wie lange diese HPA-Aktivierung anhält, sollen weitere Studien klären[1]. Originaltitel: Hypothalamic pituitary adrenal axis hormone changes during IL-17A inhibition with secukinumab in patients with psoriasis. Link zur Quelle

Menschen mit Psoriasis oder Neurodermitis schämen sich oft für ihre Haut. Diese Scham ist nicht nur unangenehm, sie beeinflusst das Leben stärker als die eigentlichen Symptome der Krankheit[1][2]. Viele Betroffene fühlen sich wegen sichtbarer Flecken ausgegrenzt, falsch beurteilt oder sogar gemieden. Manche ziehen sich zurück, weil sie Angst vor Ablehnung haben[3][4]. Forscher haben herausgefunden, dass gerade Hautscham die Lebensqualität am meisten verschlechtert – noch mehr als Depressionen oder Angst[1][5]. Jüngere Menschen und Frauen erleben Scham besonders stark. Bei Psoriasis hilft es wenig, wie lange man die Krankheit hat – entscheidend ist, wie schlimm man die eigenen Symptome findet[1]. Wer sich für seine Haut schämt, verliert oft Selbstvertrauen, fühlt sich weniger attraktiv und meidet Kontakte. Deshalb fordern Experten mehr Aufmerksamkeit für das Thema Hautscham. Sie empfehlen Hilfe und Gespräche, damit Betroffene lernen, besser mit ihren Sorgen umzugehen und wieder mehr am Leben teilhaben können[4]. Originaltitel: Shame‐related disorders in patients with atopic dermatitis and psoriasis – An exploratory, cross‐sectional interview study on the prevalence and correlates of body dysmorphic disorder and social anxiety disorder Link zur Quelle

Background and objectiveAs biologic therapy is increasingly being utilized in the treatment of paediatric psoriasis, we aim to perform a systematic review and network meta-analysis to compare the efficacy and safety of available biologic treatments for moderate to severe paediatric plaque psoriasis.MethodsRelevant randomized controlled trials (RCTs) were searched for in PubMed, Embase, Cochrane CENTRAL and clinicaltrials.gov. We performed a fixed-effects frequentist network meta-analysis (NMA) with the surface under the cumulative ranking curve (SUCRA) calculated for and mean ranking calculated. The main outcomes of interest were a ≥75% improvement in PASI score (PASI75), ≥90% improvement in PASI score (PASI90), 100% improvement in PASI score (PASI100), CDLQI score of 0/1 (CDLQI 0/1) at weeks 12-16 and safety outcomes at 12-20 weeks. Point probabilities of response were also calculated, presented as absolute risk differences per 1000 patients with their 95% CIs compared to placebo.ResultsSeven RCTs comprising 1016 psoriasis patients were included. Compared to placebo, all biologic therapies exhibited a significantly higher PASI90 and PASI75 response. Based on the SUCRA, Ixekizumab ranked highest in achieving the PASI100 (SUCRA: 0.9, Mean Rank: 1.8) response. Secukinumab high dose ranked the best for PASI90 (SUCRA: 0.8, Mean Rank: 3.0). For the CDLQI 0/1 (SUCRA: 0.8, Mean Rank: 2.2) response and the PASI75 (SUCRA: 0.9, Mean Rank: 2.2) response, standard dose Ustekinumab exhibited superior performance.ConclusionAll biologic agents (not including non-biologic comparators methotrexate and FAEs) were significantly superior to placebo, with no significant difference between individual biologic therapies, for the treatment of moderate-to-severe paediatric plaque psoriasis. Ixekizumab and Secukinumab demonstrated a trend towards a higher PASI90 response, while Ustekinumab showed a trend towards increased CDLQI and PASI75 responses. These findings highlight the need for better-powered trials in this population to determine the optimal treatment modality.Prospero numberCRD42023476983.Weiterlesen

Psoriasis is a chronic inflammatory skin disease characterized by well-demarcated erythematous plaques with silvery scales that affects 2-3% of the global population. Beyond its dermatological manifestations, psoriasis has recently been recognised as a significant cardiovascular risk factor, patients with psoriasis have an approximately 50% increased relative risk of major cardiovascular events compared with the general population. This review examines the complex relationship between psoriasis and cardiovascular disease, exploring the epidemiological evidence, underlying pathophysiological mechanisms, clinical implications and therapeutic considerations. The inflammatory milieu characteristic of psoriasis, involving T cell activation, cytokine dysregulation and systemic inflammation, creates a pro-atherogenic environment that accelerates cardiovascular disease development. Understanding the mechanisms of cardiovascular risk is crucial for clinicians managing psoriatic patients, as it necessitates comprehensive risk assessment and preventive strategies beyond traditional dermatological care.Weiterlesen

BackgroundInflammatory skin diseases including acne, atopic dermatitis, psoriasis, and psoriatic arthritis, and have become a major global public health concern. Diet's impact on inflammatory skin diseases has attracted significant attention. This study utilised the Mendelian randomization (MR) method to investigate the relationship between popular diets, such as low-calorie, vegetarian, and gluten-free diets, and several common inflammatory skin diseases.MethodsOur study employed five MR methods, including the inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode. Sensitivity analysis was conducted to confirm the accuracy and reliability of the research findings.ResultsThe results revealed a positive causal relationship between low-calorie diets and the risk of psoriatic arthritis (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01-1.10; p = 0.008) but no significant association with other diseases. No significant association was observed between vegetarian or gluten-free diets and the diseases. The reliability of the conclusion was further validated through the MR-Egger regression, MR-PRESSO analysis.ConclusionThis study offers preliminary insights into the links between diet and inflammatory skin conditions, with future large-scale, multi-method research needed to validate these findings and inform dietary recommendations.Weiterlesen

ObjectivesTo determine which anatomical sites and which ultrasonographic entheseal lesions are best able to discriminate between spondyloarthritis (SpA) patients and healthy controls (HC).MethodsWe included patients with psoriatic arthritis (PsA) and axial SpA (axSpA), from six Swiss hospital outpatient clinics, as well as HC. Participants completed quality of life and physical activity questionnaires and underwent a clinical examination of both joints and entheses, followed by a detailed musculoskeletal ultrasound examination including nine entheseal sites bilaterally. Entheses were scored according to the Outcome Measures in Rheumatology criteria, with an additional evaluation of bursae and power Doppler (PD) in the 2-5 mm zone.ResultsOverall, 121 participants were included, including 41 with PsA (mean age in years (SD), percentage male: 54.5±11.0, 63.4%), 39 with axSpA (45.1±10.0, 51.3%) and 41 HC (43.9±10.9, 56.1%), with a total of 2178 entheses evaluated. The PsA and axSpA groups showed no significant differences regarding inflammatory markers or disease activity scores.In the univariable analysis, all ultrasonographic lesions at the enthesis showed a significant association with SpA vs HC. Only B-mode inflammatory lesions (OR=1.38, p=0.034) and active enthesitis (OR=4.45, p=0.030) retained this association in multivariable analyses. While 4/9 entheses were associated with SpA in univariable analyses, only the distal patellar ligament insertion remained significantly associated with SpA (OR=1.74, p=0.039) in multivariable analyses.ConclusionTo distinguish SpA patients from controls, the sonographic scoring system used should account not only for the presence of specific entheseal lesions (structural and inflammatory) but also for the individual site affected.Weiterlesen

In psoriasis, dendritic cells activate T cells, which then release excessive pro-inflammatory cytokines, leading to abnormal growth of keratinocytes in the epidermis. At the same time, anti-inflammatory cytokines attempt to restore balance. In reality, these immune processes are not immediate; they involve biological time gaps due to signal processing, cell communication, and cytokine feedback. Such immune-related delays may play a key role in triggering unstable or oscillatory behavior observed in psoriasis flare-ups. In this study, we present and analyze a mathematical model of psoriasis that explicitly includes two intracellular immune-mediated time delays to demonstrate their biological significance in disease progression. The model captures the interactions among T cells, dendritic cells, keratinocytes, and local mature stem cells. It features two cytokine-mediated feedback loops between T cells and dendritic cells, while stem cells attempt to regulate the immune response through anti-inflammatory signaling. A key challenge is identifying the critical time delays that modulate these interactions. To address this, we introduce two different delays in different interaction terms of the model system. We test the hypothesis that these delays can critically influence the onset and persistence of psoriatic pathology mathematically. Using stability analysis of the interior equilibrium, we determine parametric relations, their ranges, and delay thresholds that give rise to Hopf bifurcations, thereby linking delays to disease and deriving conditions of instability. Our analysis demonstrates that both immune-mediated delays critically influence system stability, with threshold values of [Formula: see text] and [Formula: see text] inducing oscillations through Hopf bifurcations. Further, we apply optimal control strategies on the delayed system using the effects of two biologic agents: TNF-α and IL-17 inhibitors. Incorporation of optimal controls effectively stabilizes the immune response. Numerical simulations support these analytical findings and show that biologic interventions can effectively reduce keratinocyte density. Inclusion of immune-related delays, based on both analytical and numerical results, provides a more realistic understanding of psoriasis dynamics and helps optimize therapeutic approaches for psoriasis management.Weiterlesen

Psoriasis is a chronic, recurrent, inflammatory disease that is affected by genetic, immunological, epigenetic, and environmental factors. With the development of biotechnology, research on the pathogenesis of psoriasis has deeply focused on the field of epigenetics, and great progress has been made. Epigenetics is the study of heritable changes in gene expression or cell phenotypes without altering the DNA sequence. DNA methylation (DNAm) alterations are the most common epigenetic phenomena and are widely studied. Many studies have shown that DNAm plays a key role in the pathogenesis of psoriasis, and some differentially methylated sites may be potential targets for the treatment of psoriasis. Here, we review and summarize the recent progress on DNAm in psoriasis.Weiterlesen

BackgroundPsoriasis is a chronic, immune-mediated, inflammatory skin disease characterized by abnormal keratinocyte proliferation, in which M1 macrophage polarization plays a critical role. However, the specific biomarkers and mechanisms underlying macrophage polarization in psoriasis remain unclear.MethodsWe analyzed the psoriasis dataset (GSE14905) to identify differentially expressed genes and applied weighted gene co-expression network analysis to identify key module genes. Macrophage polarization-related (MPR) genes were extracted from the Rummagene database, and MPR genes in psoriasis were identified through Venn analysis. Functional enrichment analysis (GO/KEGG) revealed associated pathways, while six CytoHubba algorithms determined hub genes, with diagnostic potential assessed via ROC curves. Single-gene GSEA further explored biological functions, and single-cell sequencing analysis was performed. Finally, the expression of hub genes and M1 macrophage markers (CD80/CD86) was experimentally validated in psoriasis mouse models.ResultsSix hub genes (ISG15, RSAD2, IFIT3, OASL, GBP1, and IFIT1) were identified through cytoHubba algorithms. Functional enrichment analysis revealed significant associations between psoriasis-associated macrophage polarization and the RIG-I-like receptor, NOD-like receptor, and cAMP signaling pathways. Experimental validation verified the increased expression of these hub genes and M1 macrophage markers in LPS-stimulated RAW264.7 murine macrophages and IMQ-induced psoriasis animal models.ConclusionOur findings suggest that six interferon-responsive genes (ISG15, RSAD2, IFIT3, OASL, GBP1, and IFIT1) could serve as potential biomarkers for M1 macrophage polarization in psoriasis. Targeting macrophage polarization through IFN pathway inhibition may offer novel therapeutic strategies, particularly for patients with prominent IFN signatures refractory to conventional treatments.Weiterlesen

BackgroundAlthough biologic and systemic therapies have advanced psoriasis management, real-world evidence guiding individualized treatment remains limited. In particular, the influence of body size and metabolic parameters on disease severity and treatment response is underexplored.ObjectiveTo investigate the associations of body mass index (BMI), basal metabolic rate (BMR), body surface area (BSA), and body weight with baseline psoriasis severity and therapeutic response across different treatment modalities.MethodsThis multicenter, prospective study included 1955 patients from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH) and 1663 patients for longitudinal follow-up. Multivariable regression models were used to examine the associations between body size/metabolic parameters and the baseline psoriasis area and severity index (PASI) scores, as well as PASI-based treatment responses at Week 12 and Week 20. Stratified analyses by treatment type and receiver operating characteristic curve analysis were conducted to assess predictive performance.ResultsAll four parameters were positively associated with baseline PASI scores (FDR-adjusted P < 0.05). Prospectively, elevated BMI, BMR, BSA, and body weight were significantly associated with reduced likelihood of achieving PASI 75/90/100, and lower percentage reduction in PASI score at both time points. These associations were particularly pronounced in patients receiving biologic therapies. In the ustekinumab subgroup, body composition showed enhanced predictive accuracy for high-level PASI responses.ConclusionElevated BMI, BSA, body weight, and BMR are associated with more severe psoriasis and diminished treatment efficacy, especially those treated with biologics. These findings underscore the need for personalized dosing strategies in biologic therapy, especially for fixed-dose agents like ustekinumab.Weiterlesen

No abstract supplied.Weiterlesen

BackgroundTo identify new targets for protein-based treatments in psoriasis and evaluate the possible negative impacts of these druggable proteins.MethodsWe carried out an extensive analysis of the entire set of proteins in the blood (proteome-wide) to determine if there are causal links between certain blood proteins and the likelihood of developing psoriasis. The proteins were selected from the UK Biobank Pharma Proteomics Project (UKBPPP) database, which includes genetic data for 2,940 different blood proteins. We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome-wide association study (GWAS) of psoriasis.ResultsOur research discovered a strong genetic link between plasma APOF, ATP6V1G2, IFNLR1, CRELD1, PRSS8, and TNF proteins and a higher chance of having psoriasis. These proteins share genetic variations associated with psoriasis (PPH3+PPH4>0.8). The ROC curves derived from these protein quantity trait loci (pQTLs) demonstrate that they can distinguish between individuals with psoriasis and those without. The druggable gene analysis showed that simvastatin is related to TNF based on the Drug SIGnatures DataBase webtool.ConclusionOur study has explored the causal relationships between six blood proteins and psoriasis, offering a detailed insight into potential therapeutic targets. Among them, simvastatin might have an effect on psoriasis via TNF.Weiterlesen

ObjectiveSecondary failure to biologic disease-modifying antirheumatic drugs (bDMARDs) is challenging and contributes to the complexity of managing psoriatic arthritis (PsA). We aimed to define the frequency and incidence of this phenomenon in PsA and identify the risk factors for its occurrence.MethodsWe retrieved data on patients with PsA from our single-center, specialized-care, prospective observational cohort who initiated and remained on bDMARDs for ≥ 1 year after clinic enrollment between 2000 and 2023. We defined response to therapy at the 1-year visit (baseline) as achievement of ≥ 40% reduction in the swollen joint count (SJC) and either ≥ 50% reduction in Psoriasis Area and Severity Index (PASI) or PASI ≤ 2. We defined secondary failure as the inability to maintain response criteria or as the clinician's judgment of loss of effectiveness. To examine factors associated with secondary failure, we fitted Cox regression models.ResultsOf 482 patients included in the study, 264 (54.8%) were responders at 1 year. Of these, 94 (35.6%) developed secondary failure at a median of 1.6 (IQR 0.7-3.8) years from response. In the multivariable model, higher SJC (hazard ratio [HR] 1.39, 95% CI 1.05-1.84) and PASI (HR 1.14, 95% CI 1.01-1.29) at baseline were associated with secondary failure. Tumor necrosis factor inhibitors (TNFi) vs other bDMARD use (HR 0.39, 95% CI 0.18-0.88), initiation as first-line bDMARD (HR 0.48, 95% CI 0.25-0.91), and treatment initiation during more recent calendar years (HR 0.34, 95% CI 0.12-0.98) were associated with less secondary failure.ConclusionSecondary failure to bDMARD is common in PsA and may be influenced by both disease- and therapy-related factors.Weiterlesen

Objectives: To estimate the prevalence of psoriatic arthritis (PsA) and associated fac-tors in patients with moderate-to-severe psoriasis. Methods: Retrospective, single-center study of a cohort of psoriasis patients in stand-ard follow-up in a dermatology department from July 2008 to January 2024. Patients ≥18 years with moderate-to-severe psoriasis were included and classified into 3 groups according to the treatment received: group 1, biologics or small molecules with or without conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs); group 2, only csDMARDS; and group 3, non-pharmacological treatments. Demographic and clinical variables were collected. The prevalence of PsA was estimated with its 95% confidence interval (CI). The cumulative incidence of PsA was analyzed across groups, and logistic regression models were built. Results: The study population comprised 308 patients (67.2%, 22.7%, 10% in groups 1, 2, and 3, respectively). Dif-ferences between the groups were observed in severity of psoriasis, weight, smoking status, and dyslipidemia (p< 0.05). The prevalence of PsA was 11.7% (95% CI, 8.1-15.3), with most patients in group 1. This group had a high-er risk of PsA following diagnosis of psoriasis or initiation of treatment. Belonging to groups 2 and 3 had a smaller effect than belonging to group 1 in the development of PsA; nail involvement and obstructive sleep apnea (OSA) were associated with development of PsA (p< 0.05). Conclusions: The prevalence estimate was lower than previous estimates, probably owing to the increased use of biologics. Not requiring biologics for disease control had less effect on development of PsA. Nail involvement and OSA were associated with PsA.Weiterlesen

Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases associated with obesity, cardiometabolic disease, and mortality. The glucagon-like peptide-1 (GLP1) pathway has emerged as a key factor in the development of obesity and cardiometabolic disease. GLP1 receptor agonists demonstrably improve insulin resistance, dyslipidemia, obesity, and mortality, with emerging evidence suggesting potential benefit for psoriasis. To evaluate whether GLP1 biology influences psoriatic disease risk, we conducted a Mendelian randomization study. A 22-variant cis-eQTL genetic instrument for GLP1R expression in whole blood from the eQTLGen consortium was generated as a proxy for GLP1R pathway activity (n=31,684). Genetic proxies of GLP1R expression were associated with a lower risk of psoriasis (OR=0.723, 95% CI 0.678-0.771, p=1.08×10 −22 ) and PsA (OR=0.483, 95% CI 0.402-0.580, p=5.33×10 −15 ) in European-ancestry GWAS meta-analyses. Effects persisted after adjustment for genetic proxies of central adiposity, HbA1c, LDL cholesterol, and triglycerides, consistent with potential pathway effects on psoriatic disease, independent of metabolic effects. To determine the specificity of the observed effect, we conducted analyses of seven additional immune-mediated diseases (IMIDs). No protective effects were observed for other IMIDs, including acne and atopic dermatitis. In contrast, risk-increasing effects were observed for Crohn’s disease (OR=1.242, 95% CI 1.107-1.395, p=2.35×10 −4 ) and rheumatoid arthritis (OR=1.502, 95% CI 1.350-1.672, p=1.36×10 −13 ). These findings provide genetic evidence of disease-specific, potentially direct immunomodulatory effects of GLP1R signaling on psoriasis and PsA risk, and support further mechanistic and therapeutic evaluation in randomized trials.Weiterlesen

Enthesitis represents a hallmark feature and central pathological process in psoriatic arthritis and has been proposed as a potential early indicator in patients with psoriasis prior to the onset of clinically apparent psoriatic arthritis. Given the risks associated with delayed diagnosis, there is growing interest in identifying at-risk patients early to enable timely interventions and personalized treatment approaches. In clinical practice, dermatologists are often the first to encounter these patients, highlighting the need for effective screening strategies in their setting. In recent years, efforts have been made to develop validated screening tools for the early detection of musculoskeletal symptoms in patients with psoriasis. Additionally, there has been a greater focus on improving assessments through imaging techniques such as ultrasound and magnetic resonance imaging. However, a universally accepted referral pathway has yet to be established, potentially creating gaps in care during the transition from psoriasis to psoriatic arthritis. This review synthesizes current evidence on the role of enthesitis in psoriatic disease, focusing on its underlying mechanisms, diagnostic approaches, and therapeutic strategies. Importantly, we propose a practical screening and referral pathway designed to support dermatologists in early recognition of at-risk patients, with the goal of facilitating timely rheumatology referral and multidisciplinary management. By emphasizing the complementary roles of questionnaires, clinical assessment, and targeted imaging, our approach aims to bridge existing gaps in care and optimize patient outcomes.Weiterlesen