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BackgroundPsoriatic arthritis (PsA) is a complex immune-mediated heterogeneous inflammatory disease. Treatment decisions are challenging given the multisystem involvement. To further guide management strategies, we conducted a comparative analysis of the latest global guidelines highlighting the contrast in their approach to treat different PsA domains.MethodsMajor global guidelines for PsA management were reviewed, including American College of Rheumatology 2018 update, European Alliance of Associations for Rheumatology 2023 update, British Society of Rheumatology 2022, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2021, and Pan American League of Associations for Rheumatology 2024.ResultsThe guidelines unanimously recommend a treat-to-target strategy with a focus on active PsA. Divergence existed in treatment sequencing regarding the use of biologic and targeted disease-modifying antirheumatic drugs (DMARDs). Variations were also noted in the management of enthesitis and dactylitis. Addressing comorbidities and associated conditions is regarded to be a cornerstone for optimizing disease control and preventing flares.ConclusionThis review highlights the different management strategies among the global guidelines. Furthermore, we pointed at promising new therapeutic targets that are likely to be incorporated into future recommendations.Weiterlesen

BackgroundPolycyclic aromatic hydrocarbons (PAHs) are environmental pollutants with widespread human exposure and have been associated with adverse health outcomes. However, their potential relationship with psoriasis remains insufficiently explored.ObjectiveThe aim of this study is to investigate the association between PAH exposure and psoriasis.MethodsData were obtained from the National Health and Nutrition Examination Survey (NHANES) for the periods 2005-2006, 2009-2010, and 2011-2012. Weighted multivariate logistic regression analysis was performed to assess the association between individual PAH metabolites and psoriasis. Bayesian kernel machine regression (BKMR), quantile g-computation (qgcomp), and weighted quantile sum (WQS) regression were used to evaluate the relationship between mixed PAH exposure and psoriasis, as well as to determine the relative contributions of specific PAH metabolites. Stratified and sensitivity analyses were conducted to assess result stability.ResultsA total of 4,912 participants (mean age, 43.52 years; 95% CI, 42.65-44.39 years) were included, of whom 2,514 (51.18%) were female, and 141 (2.87%) were diagnosed with psoriasis. Multivariate logistic regression analysis identified significant positive associations between psoriasis and seven urinary PAH metabolites: 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 3-hydroxyphenanthrene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, and 1-hydroxypyrene. Analysis of mixed exposure PAH across all three models demonstrated significant positive associations between urinary PAH metabolites and psoriasis, with 2-hydroxyphenanthrene and 2-hydroxynaphthalene identified as primary contributors. Stratified and sensitivity analyses confirmed the robustness of these results, and the observed associations persisted among non-smokers.ConclusionBoth single and mixed exposure analyses demonstrated a positive association between PAH exposure and psoriasis. These findings suggest that reducing PAH exposure may help mitigate psoriasis risk.Weiterlesen

ContextEvidence regarding the relationship between serum trace element levels and immune-mediated inflammatory skin diseases (IMSDs) is inconsistent.ObjectiveIn this systematic review and meta-analysis we aimed to evaluate the association between selected serum trace element levels (zinc [Zn], copper [Cu], iron [Fe], selenium [Se], and calcium [Ca]) and IMSDs (psoriasis, vitiligo, atopic dermatitis [AD], alopecia areata [AA], hidradenitis suppurativa, and bullous diseases).Data sourcesWe conducted a comprehensive search on the PubMed, EMBASE, Scopus, China National Knowledge Infrastructure, and Web of Science databases from the database inception date to May 2, 2024. Studies measuring serum, plasma, or whole-blood levels of Zn, Cu, Fe, Se, or Ca in patients with IMSD compared to those in healthy controls were included.Data extractionThis study followed the guidelines of the Meta-analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Two authors (X.Y.S. and Y.O.) independently reviewed the titles and abstracts of the identified studies using a standardized collection form.Data analysisThe primary outcome was the standardized mean difference with a 95% CI in serum trace element levels (Zn, Cu, Fe, Se, and Ca) between patients with IMSDs and healthy controls. Overall, 113 studies involving 7014 patients with IMSD were included in the meta-analysis. Compared with those in the healthy control group, serum Zn levels decreased in patients with vitiligo, psoriasis, and AA; serum Cu levels increased in patients with psoriasis, AD, and AA; serum Se and Fe levels decreased in patients with psoriasis and AD.ConclusionSerum trace element levels showed more significant changes in patients with IMSDs than in healthy controls. These findings suggest that alterations in trace element levels may be associated with the occurrence, development, and prognosis of IMSDs.Weiterlesen

BackgroundPsoriasis is a chronic skin disease affecting millions of people, with obesity being a common comorbidity. Many studies suggest that obesity may influence the onset and treatment efficacy of psoriasis. Currently, increasing evidence indicates that abdominal obesity is associated with various metabolic diseases, but research on the relationship between abdominal obesity and psoriasis remains limited. This study uses advanced obesity indicators such as the conicity index and body roundness index to explore the association between abdominal obesity and psoriasis.MethodsThis study is a cross-sectional analysis that uses univariate regression analysis and weighted multivariable logistic regression to investigate the relationship between conicity index, android percent fat, body roundness index, and psoriasis. Additionally, restricted cubic spline analysis was performed to explore the nonlinear association between these indicators and psoriasis. Subgroup analysis and interaction tests were also conducted.ResultsA total of 4873 participants were included in this study. After adjusting for confounding variables, the results showed a positive correlation between conicity index, android percent fat, body roundness index, and the risk of psoriasis. When conicity index, android percent fat, and body roundness index were converted into quartiles (Q1-Q4), the risk of psoriasis in the Q4 group was significantly higher compared to the Q1 group (conicity index: p = 0.032, android percent fat: p = 0.020, body roundness index: p = 0.003). In the subgroup analysis and interaction tests, no significant interaction between the conicity index, body roundness index, and the association with psoriasis was found (p > 0.05). The results only suggest that the poverty income ratio (PIR), marital status, and alcohol consumption may influence the relationship between android percent fat and psoriasis. In addition, subgroup analysis based on age shows that the association between abdominal obesity and psoriasis is more significant in the population over 40 years old.ConclusionsAfter adjusting for covariates, the study found that three abdominal obesity indicators-conicity index, android percentage fat, and body roundness index-are positively correlated with psoriasis risk, suggesting that the association between abdominal obesity and psoriasis as a comorbidity is more likely to occur, emphasizing the clinical significance of this link.Level of evidenceLevel III, Evidence obtained from well-designed cohort or case-control analytic studies.Weiterlesen

Psoriatic disease encompasses psoriasis and psoriatic arthritis. It is a chronic, progressive condition and leads to irreversible joint destruction. Conventional treatments used are disease-modifying antirheumatic drugs and biologics. Janus kinase (JAK) signal transducers and activators of transcription (STAT) cell signaling protein inhibitors have shown promising results in psoriatic disease. However, JAK inhibitors have been associated with some concerning safety issues, such as cardiac risks, venous thrombotic episodes, malignancy, and infection. There are other developing molecules beyond JAK inhibitors, such as tyrosine kinase 2 (TYK2) inhibitors, RAR-related orphan receptor gamma (RORγ) inhibitors, mammalian target of rapamycin inhibitors, nerve growth factor inhibitors, and STAT kinase inhibitors. In this narrative review, we have discussed such molecular targets beyond JAK inhibitors to examine their role in the treatment of psoriatic disease. This review discusses the potential of these new options, particularly TYK2 inhibitors, which is already Food and Drug Administration approved for psoriasis. These advancements offer promising options for the management of psoriatic disease.Weiterlesen

Due to their similar clinical presentations, the scarcity of competent dermatologists, and the urgency of diagnosis, the accurate diagnosis of dermatological conditions such as Psoriasis and Lichen Planus is challenging. This study introduces a novel approach leveraging deep learning and numerical simulations of skin biomechanical properties to enhance diagnostic precision. By utilizing ABAQUS software, this study incorporates 1000 numerical simulations for data generation to combat the limitations of datasets in these ailments. Utilizing the ResNet-50 convolutional neural network (CNN), this research integrates data from finite element simulations based on variations in skin's biophysical parameters. The dataset comprises 1000 instances, evenly divided between Psoriasis and Lichen Planus, with attributes including displacement, humidity, age, and sex. The numerical data were converted into image data to optimize the ResNet-50 model's performance. The results were validated through 5-fold cross-validation, 3-fold cross-validation, and random splitting. The proposed methodology demonstrated remarkable diagnostic accuracy, achieving 99.8% using 5-fold cross-validation, surpassing previous investigations, and highlighting the potential of combining AI and biomechanical simulations for real-time skin disease diagnosis to assist physicians and dermatologists in classifying skin diseases.Weiterlesen

Psoriatic patients have shown higher levels of neutrophil extracellular traps (NETs) vs healthy controls. Psoriasis is often associated with other comorbidities such as cardiovascular disease. An increase in indirect markers of NETs has been found in patients with increased cardiovascular events in patients without psoriasis.We conducted a prospective observational study with psoriatic patients. A total of 39 of patients were included. Myeloperoxidase, neutrophil elastase and double-stranded DNA were significantly higher in patients with severe-to-moderate vs mild psoriasis. Myeloperoxidase was also significantly higher in patients of moderate high vs low cardiovascular risk (p = .01) in patients with mild psoriasis. Patients with psoriatic arthritis show higher myeloperoxidase levels higher vs those without arthritis (p = .048). Myeloperoxidase was also significantly correlated (p = .0375) with the patients' BMI.The detection of NETs through indirect markers (Myeloperoxidase, neutrophil elastase and double-stranded DNA) is associated with the severity of psoriasis. In addition, myeloperoxidase can be useful in psoriatic patients as biomarkers of comorbidities.Weiterlesen

Psoriasis is a chronic inflammatory autoimmune skin disease with enhanced skin cell turnover. Despite the therapies currently available, better and target-oriented therapies are needed. Fisetin is a flavonoid with antioxidant, anti-inflammatory, and immunomodulatory properties. It shows therapeutic potential, but its poor bioavailability and penetration into the skin cannot be used effectively to treat psoriasis. While fisetin-loaded nanoformulations in cancer and other diseases have been explored, their potential as a therapy for psoriasis is unexplored. Most reviews detail the biological activities of fisetin or nanoformulations for psoriasis therapy but not their combination. The review here compiles fisetin's chemical and pharmacological properties along with the problems with conventional drug delivery and fisetin-loaded nanoformulations such as polymeric nanoparticles, liposomes, solid lipid nanoparticles, nanogels, and micelles. It also discusses their mechanisms, preclinical results, and potential for the clinic. Preclinical studies demonstrate fisetin nanoformulations to enhance penetration into the skin, reduce inflammation, promote skin regeneration in psoriasis models, and alleviate symptoms of redness and scaling. Clinical trials are lacking, and studies are needed to assess safety and efficacy. Fisetin nanoformulations are a potential target-oriented psoriasis therapy with better drug delivery and fewer side effects than conventional therapies. Despite formulation stability, scalability, and regulatory issues, the potential for fisetin-loaded nanoformulations is excellent and needs further exploration for their safety and efficacy in patients.Weiterlesen

No abstract supplied.Weiterlesen

In der FASTLANE-Studie wurde untersucht, wie wirksam und sicher **Tofacitinib** bei Menschen mit früher, aktiver axialer Spondyloarthritis ist. Axiale Spondyloarthritis ist eine chronisch-entzündliche Erkrankung, die vor allem die Wirbelsäule und das Kreuz-Darmbein-Gelenk betrifft und zu Rückenschmerzen sowie Bewegungseinschränkungen führen kann. Die Studie richtete sich an Erwachsene im Alter von 18 bis 64 Jahren, deren Rückenschmerzen höchstens zwei Jahre bestanden und die auf mindestens ein nicht-steroidales Antirheumatikum (NSAID) nicht ausreichend angesprochen hatten. Die Teilnehmenden wurden zufällig entweder mit Tofacitinib oder einem Placebo behandelt – beide Gruppen erhielten zusätzlich Naproxen als Hintergrundtherapie. Ziel war es herauszufinden, wie viele Patientinnen und Patienten nach 16 Wochen eine Krankheitsremission erreichten (definiert über einen speziellen Aktivitätswert für Spondyloarthritis). Außerdem wurde per MRT gemessen, wie stark die Entzündung in den Gelenken zurückging. **Tofacitinib** ist ein sogenannter Januskinase-(JAK)-Inhibitor. Das bedeutet: Es hemmt gezielt bestimmte Signalwege im Immunsystem, die bei Entzündungsreaktionen eine Rolle spielen. Der Wirkstoff wird bereits zur Behandlung anderer entzündlicher Erkrankungen eingesetzt – etwa rheumatoider Arthritis oder Colitis ulcerosa – und liegt hier als Tablette vor. Originaltitel: Tofacitinib in early active axial spondyloarthritis: a prospective, randomized, double-blind, placebo-controlled multicentre study - FASTLANE Erkrankung: Axiale Spondyloarthritis Phase: IV Firma: Charité Universitätsmedizin Berlin KöR Art der Verabreichung: Tablette https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505050-18-00

Eine neue Studie zeigt, dass es einen **direkten Zusammenhang zwischen bestimmten Autoimmunerkrankungen und dem Risiko für Unfruchtbarkeit bei Frauen** gibt[1]. Die Forschenden haben dabei eine Methode namens Mendelsche Randomisierung genutzt. Das klingt kompliziert, heißt aber einfach, dass sie genetische Daten untersucht haben. Damit können sie ziemlich sicher sagen: Die Verbindung liegt nicht nur an Lebensstil oder Umwelt, sondern steckt tatsächlich in den Genen. Zum Beispiel fanden sie, dass Frauen mit **Zöliakie, Vitiligo oder Lupus** ein erhöhtes Risiko für eine sogenannte primäre Ovarialinsuffizienz haben. Das bedeutet, dass die Eierstöcke früh ihre Funktion einstellen, was zu Unfruchtbarkeit führen kann. Überraschend: Bei Frauen mit selektivem IgA-Mangel könnten die Gene sogar einen schützenden Effekt haben[1]. Das Wissen hilft, Frauen mit Autoimmunerkrankungen früher zu beraten, wenn es um Kinderwunsch geht. Originaltitel: Mendelian randomization analysis reveals causal associations between autoimmune diseases and female infertility risk Link zur Quelle

Einige Menschen mit Psoriasis-Arthritis können tatsächlich für längere Zeit ohne Medikamente wie DMARDs auskommen. Das zeigt eine neue Studie aus den Niederlanden. Dort wurden 451 Betroffene nach ihrer Diagnose mehrere Jahre lang beobachtet. Rund 22 Prozent schafften es, mindestens drei Monate nach dem Absetzen frei von Gelenkentzündungen zu bleiben. Doch wirklich dauerhaft, also länger als ein Jahr ohne Rückfall, schafften das nur etwa 9 Prozent. Diese Personen hatten oft von Anfang an eine eher milde Erkrankung und keine Biologika gebraucht[1][3]. Trotzdem: Bei den meisten kam die Krankheit nach dem Absetzen der Medikamente zurück, oft schon nach kurzer Zeit[2]. Wer seine Therapie beenden will, sollte das nur in Rücksprache mit dem Arzt tun und regelmäßig kontrollieren lassen. Originaltitel: Disease-modifying antirheumatic drug–free remission in psoriatic arthritis: is it attainable and sustainable? A large longitudinal study Link zur Quelle

Forscher haben untersucht, wie oft Autoimmunerkrankungen wie **Psoriasis** in verschiedenen Ländern vorkommen und ob das irgendwie mit der Durchschnittstemperatur zusammenhängt. Dabei zeigte sich: Es gibt tatsächlich einen deutlichen Zusammenhang zwischen Klima und Autoimmunerkrankungen wie Typ-1-Diabetes, Rheumatoider Arthritis, Psoriasis und chronisch-entzündlichen Darmerkrankungen. In Ländern mit anderen Temperaturen unterscheidet sich auch die Häufigkeit dieser Krankheiten[1]. Warum das so ist, wissen die Wissenschaftler noch nicht genau. Wahrscheinlich spielen nicht nur die Gene, sondern auch Umweltfaktoren wie die Temperatur und andere Klimaeinflüsse eine Rolle dabei, ob jemand eine Autoimmunerkrankung entwickelt. Das Ganze ist ziemlich komplex und es braucht noch mehr Forschung, um alle Zusammenhänge zu verstehen[1]. Klar ist: Klima und Temperatur können das Immunsystem beeinflussen – das gilt auch für Psoriasis. Originaltitel: Prevalence of autoimmune diseases is strongly associated with average annual temperatures: systematic review and linear regression analysis - BMC Rheumatology Link zur Quelle

Eine Studie hat untersucht, wie sich eine Schwangerschaft auf die Krankheitsaktivität bei rheumatoider Arthritis (RA) und Psoriasisarthritis (PsA) auswirkt. Dabei wurden Ultraschalluntersuchungen genutzt. Das Ergebnis: Bei schwangeren Frauen mit RA waren die Krankheitssymptome laut Testwerten und Ultraschall niedriger als bei nicht schwangeren Frauen mit RA. Bei schwangeren Frauen mit PsA wirkten die Testwerte zwar besser, doch im Ultraschall zeigte sich mehr Aktivität, besonders im späteren Verlauf der Schwangerschaft. Die betroffenen Schwangeren schätzten ihren Gesundheitszustand oft besser ein als nicht schwangere Patientinnen. Ultraschall kann helfen, die Krankheit in der Schwangerschaft genauer zu überwachen[1]. Originaltitel: Deciphering the influence of pregnancy on rheumatoid arthritis and psoriatic arthritis: insights from musculoskeletal ultrasound dynamics. Link zur Quelle

Menschen mit Psoriasis haben ein etwas erhöhtes Risiko für bestimmte Krebsarten. Die Behandlung von Psoriasis bei Betroffenen, die schon einmal Krebs hatten, ist schwierig, weil es kaum Daten gibt, wie sicher Biologika in diesem Fall sind. Aktuelle Studien zeigen: **IL-23-Inhibitoren** scheinen auch für Menschen mit einer Krebs-Vorgeschichte sicher zu sein[2]. In einer großen Untersuchung hatten Patienten, die solche Medikamente einnahmen, nur selten einen Rückfall, eine Verschlechterung oder eine neue Krebserkrankung[2]. Die Rate war nicht höher als bei anderen Patienten mit Psoriasis[2]. Auch andere Berichte bestätigen: **IL-23-Inhibitoren helfen gegen Psoriasis und scheinen das Krebsrisiko nicht zu erhöhen**[1][3]. Fachleute empfehlen deshalb, die Situation individuell mit dem Arzt zu besprechen. Noch größere Studien wären hilfreich, um die Sicherheit eindeutig zu belegen[2]. Originaltitel: Psoriasis vulgaris in patients with a recent history of neoplasia: safety of interleukin-23 inhibitors. A multicentre retrospective study | Clinical and Experimental Dermatology | Oxford Academic Link zur Quelle

In der Studie "EffisayilTM ON" wird untersucht, wie sicher und wirksam die Substanz **Spesolimab** bei Menschen mit generalisierter pustulöser Psoriasis (GPP) ist. GPP ist eine seltene, chronische Hautkrankheit, bei der es immer wieder zu schweren Schüben mit schmerzhaften, eitrigen Bläschen kommt. Diese Krankheit kann lebensbedrohlich sein und die Lebensqualität stark beeinträchtigen. **Spesolimab** ist ein sogenannter monoklonaler Antikörper – das heißt, es handelt sich um ein biotechnologisch hergestelltes Eiweißmolekül, das gezielt einen bestimmten Entzündungsweg im Körper blockiert. Konkret richtet sich Spesolimab gegen den Interleukin-36-Rezeptor (IL-36R), der eine zentrale Rolle bei den Entzündungsprozessen in GPP spielt. Durch diese Blockade kann die überschießende Immunreaktion gestoppt werden: Die Bildung von Eiterbläschen und weitere Symptome wie Fieber oder Schmerzen werden reduziert. Die bisherigen Studien zeigen bereits, dass Spesolimab sehr schnell wirkt und sowohl die Hautsymptome als auch das allgemeine Wohlbefinden verbessert. In dieser offenen Langzeitstudie wird nun weiter geprüft, wie gut das Medikament über einen längeren Zeitraum vertragen wird und ob es langfristig hilft, neue Krankheitsschübe zu verhindern. Originaltitel: EffisayilTM ON: An open-label, long term extension study to assess the safety and efficacy of spesolimab treatment in patients with Generalized Pustular Psoriasis (GPP) Erkrankung: Generalisierte pustulöse Psoriasis (GPP) Phase: Phase II (therapeutisch-exploratorisch) Firma: Boehringer Ingelheim International GmbH / Boehringer Ingelheim Espana S.A. Art der Verabreichung: Injektion https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-509216-28-00

Psoriasis is a chronic skin disease affecting millions of people, with obesity being a common comorbidity. Many studies suggest that obesity may influence the onset and treatment efficacy of psoriasis. Currently, increasing evidence indicates that abdominal obesity is associated with various metabolic diseases, but research on the relationship between abdominal obesity and psoriasis remains limited. This study uses advanced obesity indicators such as the conicity index and body roundness index to explore the association between abdominal obesity and psoriasis. This study is a cross-sectional analysis that uses univariate regression analysis and weighted multivariable logistic regression to investigate the relationship between conicity index, android percent fat, body roundness index, and psoriasis. Additionally, restricted cubic spline analysis was performed to explore the nonlinear association between these indicators and psoriasis. Subgroup analysis and interaction tests were also conducted. A total of 4873 participants were included in this study. After adjusting for confounding variables, the results showed a positive correlation between conicity index, android percent fat, body roundness index, and the risk of psoriasis. When conicity index, android percent fat, and body roundness index were converted into quartiles (Q1-Q4), the risk of psoriasis in the Q4 group was significantly higher compared to the Q1 group (conicity index: p = 0.032, android percent fat: p = 0.020, body roundness index: p = 0.003). In the subgroup analysis and interaction tests, no significant interaction between the conicity index, body roundness index, and the association with psoriasis was found (p > 0.05). The results only suggest that the poverty income ratio (PIR), marital status, and alcohol consumption may influence the relationship between android percent fat and psoriasis. In addition, subgroup analysis based on age shows that the association between abdominal obesity and psoriasis is more significant in the population over 40 years old. After adjusting for covariates, the study found that three abdominal obesity indicators-conicity index, android percentage fat, and body roundness index-are positively correlated with psoriasis risk, suggesting that the association between abdominal obesity and psoriasis as a comorbidity is more likely to occur, emphasizing the clinical significance of this link. Level III, Evidence obtained from well-designed cohort or case-control analytic studies.Weiterlesen

BackgroundPsoriasis patients frequently present with cardiovascular comorbidities, which maybe associated with abnormal epicardial adipose tissue (EAT). This study aimed to evaluate the predictive value of radiomics features derived from non-contrast chest CT (NCCT) combined with serological parameters for identifying abnormal EAT in psoriasis.MethodsIn this retrospective case-control study, we enrolled consecutive psoriasis patients who underwent chest NCCT between September 2021 and February 2024, along with a matched healthy control group. Psoriasis patients were stratified into mild-to-moderate (PASI ≤ 10) and severe (PASI > 10) groups based on the Psoriasis Area and Severity Index (PASI). Using TIMESlice, we extracted EAT volume, CT values, and 86 radiomics features. The cohort was randomly divided into a training (70%) and test (30%) set. LASSO regression selected radiomic features to calculate the Rad_Score. Serum uric acid (UA) and C-reactive protein (CRP) levels were collected. We compared EAT volume, CT values, Rad_Score, UA, and CRP between groups and developed three models: Model A (UA, CRP, EAT CT values), Model B (Rad_Score), and Model C (UA, CRP, EAT CT values, Rad_Score). Model accuracy was evaluated using ROC curves (P < 0.05).ResultsThe study included 77 psoriasis patients and 76 matched controls. Psoriasis patients had higher UA and CRP levels than controls (both P < 0.001). EAT CT value was higher in psoriasis (P = 0.020), with no volume difference. Eight radiomics features and Rad_Score significantly differed between groups (P < 0.001), and Rad_Score also higher in severe group than that in mild-to-moderate group (P < 0.001). Model C showed the highest AUC in both sets: training 0.947 and test 0.895, indicating superior predictive performance.ConclusionsCombining radiomics features, EAT CT values, UA, and CRP in a predictive model accurately predicts EAT abnormalities in psoriasis, potentially improving cardiovascular comorbidity diagnosis.Clinical trial numberNot applicable.Weiterlesen

IntroductionThe International Psoriasis Council (IPC) reclassified patients eligible for systemic therapy to include those with body surface area (BSA) > 10%, psoriasis lesions in high-impact areas, or failure of topical therapy. Risankizumab is an interleukin-23 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis. This retrospective study evaluated the real-world effectiveness of risankizumab in patients with BSA 3-10% and patients meeting IPC systemic therapy criteria, addressing existing gaps in knowledge regarding its effectiveness in these patient groups.MethodsBiologic-naïve adults with moderate-to-severe plaque psoriasis who initiated risankizumab between April 2019 and August 2023 and were treated for 12 (± 3) months were identified from the CorEvitas Psoriasis Registry and stratified by baseline BSA. At 12 months, skin clearance was assessed by achievement of Psoriasis Area Severity Index (PASI) 90, PASI 100, and National Psoriasis Foundation (NPF) treat-to-target goals. Patient-reported outcomes (PROs) included achievement of Dermatology Life Quality Index (DLQI) 0/1, improvements in psoriasis symptoms, and work and activity impairment.ResultsOf 272 patients analyzed, 123 had BSA 3-10% (78 had any high-impact area involvement and 105 had prior topical therapy experience) and 149 patients had BSA > 10%. Among those with BSA 3-10%, 77.9% achieved PASI 90 and 67.2% achieved PASI 100. NPF acceptable and target responses were met by 95.3% and 87.9%, respectively. Regarding PROs, 68.1% of patients with moderate skin involvement (BSA 3-10%) attained a DLQI score of 0/1. Significant improvements from baseline in psoriasis symptoms and reductions in work and life impairments were also reported (P < .001). Comparable positive outcomes were observed across all IPC systemic therapy eligible patient subgroups.ConclusionIn patients with BSA 3-10% and those systemic-eligible per IPC classification, continuous treatment with risankizumab for 12 months resulted in high levels of skin clearance and improvements in PROs.Weiterlesen

BackgroundPsoriasis is an inflammatory disorder characterized by scaly erythematous plaques and significant comorbidities. Recent studies have suggested that impaired mitophagy, the cellular mechanism for removing dysfunctional mitochondria, may contribute to the pathogenesis of psoriasis.MethodsIn this study, we analyzed bulk RNA sequencing data from 167 healthy individuals and 177 patients with psoriasis obtained from the Gene Expression Omnibus database (GSE30999 and GSE54456). Mitophagy-related genes were isolated using weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed and protein-protein interaction networks were constructed for the functional enrichment of genes associated with mitophagy. The correlations between genes associated with mitophagy, signaling pathways, and immune cell infiltration were analyzed. The potential diagnostic value of genes associated with mitophagy was evaluated using receiver operating characteristic (ROC) curves, which were validated in imiquimod-induced psoriatic skin lesions in mice.ResultsWe identified 3,839 differentially expressed genes between healthy individuals and patients with psoriasis, and 23 genes were selected as hub genes showing a high correlation with mitophagy in psoriasis. GO and KEGG analyses revealed that hub and associated genes were significantly correlated with skin functions, such as epidermal development and keratinocyte differentiation. In addition, mitophagy-related genes were negatively associated with pro-inflammatory and pro-proliferation pathways in psoriasis. Among the immune cells, CD4+ T cells were most significantly affected by mitophagy-related genes. ROC analysis demonstrated that mitophagy-related genes, especially ACER1, C1ORF68, CST6, FLG2, GJB3, GJB5, GPRIN2, KRT2, and SPRR4 were potential biomarkers of psoriasis for use in diagnosis or treatment.ConclusionsMitophagy-related genes play crucial roles in psoriasis and have potential use as biomarkers, providing insights into disease mechanisms and therapeutic targets. Further research may lead to the development of new strategies for psoriasis management.Weiterlesen

BackgroundPlacebo effects are a significant challenge in the conduct of clinical trials. We explored how global recruitment patterns influence the extent of placebo responses in randomized controlled trials of psoriatic arthritis and plaque psoriasis.MethodsWe conducted an analysis of 51 trials (6,843 patients; 52±5.7% female) in psoriatic arthritis, and 43 trials (5,671 patients; 32±7.1% female) in plaque psoriasis investigating biological and targeted synthetic therapeutics. We investigated to what extent global recruitment patterns are related to the extent of response rates in the placebo arms of these clinical trials by investigating underlying socioeconomic factors using the average per capita gross national income (GNI; weighted for recruiting study centers per country) as proxy of these patterns in linear mixed models.FindingsWe identified a negative association of GNI and placebo response rates on the primary endpoints across psoriatic arthritis trials (ACR20: β=-5.7% per 10,000 international Dollars; 95% CI: -7.8% to -3.5%; p<0.001) and plaque psoriasis trials (PASI75%: β=-1.1%; 95% CI: -2.0 to -0.3; p=0.011). Sensitivity analyses using other outcome measures and alternative economic metrics, such as the UN Human Development Index and WHO out-of-pocket health expenditures were confirmatory.InterpretationThe global expansion of trial recruitment to less affluent countries may increase placebo rates in studies of psoriatic arthritis and plaque psoriasis. These higher placebo rates may reflect the higher perceived benefit in these countries, leading to regression to the mean after patients have been successfully enrolled.Weiterlesen

ObjectivesConflicting data exist on TNF inhibitors' (TNFi) role in preventing psoriatic arthritis (PsA) in psoriasis. Using propensity score matching, we compared PsA incidence in severe psoriasis patients treated with TNFi versus narrow-band ultraviolet B (nbUVB) phototherapy over a decade of follow up.MethodsConsecutive adults with severe psoriasis prescribed TNFi or nbUVB phototherapy between September 2005 and September 2010 were enrolled. Of 946 patients, 497 received TNFi (median follow-up 9.6±2.6 years) and 449 underwent nbUVB (9.4±5.9 years). All had rheumatologist assessment before therapy and for PsA diagnosis. PS matching adjusted for factors linked to PsA, including arthralgia, family history, BMI, PASI, and psoriasis distribution, including nails.ResultsAfter propensity score matching, the TNFi cohort contributed 2705.5 person-years of follow-up (mean 9.1 ± 2.9 years), and the nbUVB cohort 2654.1 person-years (mean 8.9 ± 5.4 years). The PsA incidence rate per 100 patients was 1.18 (0.84-1.52) in the TNFi group and 2.48 (2.24-2.72) in the nbUVB group, yielding an incidence rate ratio of 2.1 (1.37-2.98, p = 0.0002). A time-dependent Cox model confirmed that TNFi treatment was associated with a significantly lower risk of PsA (HR = 0.32, p < 0.0001). Arthralgia (HR = 7.68, p < 0.0001), nail psoriasis (HR = 1.93, p = 0.0004), and higher PASI score (HR = 1.03 per point, p = 0.0096) were independent predictors of PsA.ConclusionThis PS-matched study shows a clear benefit of TNFi versus nbUVB in PsA reduction in severe psoriasis patients over nearly a decade of therapy.Weiterlesen

ObjectivePsoriatic arthritis (PsA) is a chronic immune-mediated inflammatory arthritis that develops in 30% of patients with psoriasis, leading to increased morbidity and mortality and reduced quality of life. MicroRNAs (miRNAs) modulate gene expression and have been associated with the pathogenesis of immune-mediated disorders. We aimed to identify miRNAs that can be used as biomarkers for the development of PsA in patients with psoriasis.MethodsmiRNA expression levels were assessed in serum samples from 28 patients with PsA, 35 patients with cutaneous psoriasis without arthritis (PsC), and 28 healthy controls through next-generation sequencing. Differential expression was assessed by linear modeling with empirical Bayes moderation corrected for sequencing batch, age, sex, and duration of psoriasis. For validation, we measured the expression of >191 genes predicted to be targeted by the dysregulated miRNAs using a custom NanoString probe panel in an independent cohort of 144 patients with PsA and 88 patients with PsC. The enrichment of specific pathways corresponding to the differentially expressed gene targets was examined using pathDIP.ResultsIn the discovery cohort, the miRNA miR-190a-5p was significantly down-regulated in patients with PsA compared to those with PsC (P< 0.05), and both miR-190a-5p and miR-26b-5p were down-regulated in patients with PsA versus healthy controls (P < 0.05). In the validation cohort, 26 gene targets of both of these miRNAs were differentially expressed. These genes were enriched in signaling pathways associated with bone formation and regeneration: Wnt and transforming growth factor β.ConclusionSerum expression levels of miR-190a-5p and miR-26b-5p can potentially serve as biomarkers for PsA development.Weiterlesen

Psoriasis is a chronic inflammatory skin disease with a high world-wide incidence. Rutin, a natural citrus flavonoid glycoside, has been shown to have anti-inflammatory and antioxidant properties. To investigate the protective effects of rutin in imiquimod (IMQ)-induced psoriasis model mice and its underlying molecular mechanism. IMQ was applied to mice to induce inflammatory skin that phenotypically mimics psoriasis. The Psoriasis Area Severity Index (PASI) score was used to evaluate the degree of erythema, scale and thickening of skin lesions. The inflammatory cytokines and oxidative stress factors were measured to evaluate the anti-inflammatory and antioxidant effects of rutin. Finally, experiments were performed using Nrf2-deficient mice to determine the underlying molecular mechanism of rutin in the treatment of psoriasis. Mice treated with rutin showed reduced erythema, scaling, and epidermal thickening compared to mice without treatment. In skin tissue, topical administration of rutin inhibited the IMQ-induced increases in reactive oxygen species, nitric oxide, and malondialdehyde, and significantly increased the IMQ-induced decreases in total antioxidant capacity, superoxide dismutase, and glutathione peroxidase. Additionally, the expression levels of the pro-inflammatory cytokines IL-6, IL-1β, IL-17A, and IL-23A were significantly increased in the IMQ-treated group compared to the control group, but were significantly reduced by rutin. Importantly, Nrf2-deficient mice exhibited aggravated psoriasis-like symptoms and reduced response to rutin treatment. Our data evidence that rutin ameliorated IMQ-induced psoriasis-like skin lesions by inhibiting oxidative stress injury and the inflammatory response via the Keap1/Nrf2 pathway, suggesting a potential therapeutic role for rutin in the psoriasis treatment.Weiterlesen

ObjectivesLittle is known about the ideal service delivery model and shortcomings in patient experiences in the NHS for patients with psoriatic arthritis (PsA). The objective of this work was to identify unmet needs perceived within the current health service delivery model for PsA from the UK Psoriatic Arthritis Priority Setting Partnership (PsA-PSP).MethodsAn online survey was conducted in 2020 and distributed to people with PsA, their carers and clinicians to identify research priorities in PsA. The participants were asked to submit three questions unanswered in PsA research. A proportion of submissions related to health service delivery were identified, which were deemed as out of scope for the main PsA-PSP but nevertheless important to report. Content analysis was used to analyse these submissions separately.ResultsWe reviewed 138 submissions that were not related to the James Lind PSP and research priorities in PsA. Among these, 118 (85.5%) were focused on health service delivery and were classified into five main themes: rheumatology service, primary care navigation, education, holistic care, and ethnicity, diversity and inclusion. Further analysis within the rheumatology service theme revealed additional sub-themes that emphasized integrating multidisciplinary services, improving access to advice lines and ensuring fair access to treatments.ConclusionThe five key themes provide valuable insights into the important areas of interest within health service delivery in the UK. By understanding these themes, policymakers, healthcare providers and researchers can better prioritize their efforts and address the specific care needs of people with PsA, their care providers and clinicians.Weiterlesen