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Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with psoriasis and characterised by heterogeneous clinical manifestations, including peripheral and axial arthritis, enthesitis and dactylitis. A subset of patients exhibits a 'difficult-to-treat' (D2T) phenotype, necessitating complex therapeutic strategies. Metabolic syndrome (MetS) is highly prevalent in PsA patients and has been implicated in increased disease activity.This study aimed to evaluate the impact of MetS on the development of D2T phenotype in PsA and its potential implications for disease management.Methods
A cross-sectional study was conducted on PsA patients recruited from the Rheumatology Clinic at Fondazione Policlinico Campus Bio-Medico of Rome. Patients fulfilling the Classification Criteria for Psoriatic Arthritis criteria were assessed for disease activity and the presence of MetS according to National Cholesterol Education Programme Adult Treatment Panel III criteria. D2T PsA was defined based on the Rheumatoid Arthritis European Alliance of Associations for Rheumatolog criteria revised for PsA by Perrotta et al. Statistical analyses, including logistic regression and path analysis, were performed to explore associations between MetS and D2T PsA.Results
Among 182 PsA patients, 42.94% met MetS criteria. The D2T subset (n=66) demonstrated a significantly higher prevalence of MetS (81.82% vs 29.37%, p<0.0001). Logistic regression revealed a strong association between MetS and D2T PsA (OR 7.56, 95% CI 2.53 to 22.56, p<0.0001), and path analysis confirmed MetS as an independent predictor of D2T phenotype.Conclusions
MetS is strongly associated with a D2T phenotype in PsA, suggesting that metabolic comorbidities contribute to disease severity and treatment resistance. Addressing metabolic dysfunction may be crucial in optimising therapeutic outcomes in PsA management.Weiterlesen
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The mechanism of action of treatment drugs for psoriasis is based on anti-inflammation and the inhibition of epidermal proliferation, and retinoids and vitamin D3 derivatives are first-line therapy drugs for psoriasis. This meta-analysis aimed to comprehensively evaluate the efficacy and safety of calcipotriol-acitretin combination therapy for psoriasis and investigate its effect on serum inflammatory factors.Methods
A systematic search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese biomedical literature service system (SinoMed), and Chinese Biomedical Journal Database (VIP), from the earliest record until Dec.13, 2024, was conducted. The outcomes were overall effective rate, Psoriasis Area and Severity Index (PASI) scores, inflammatory factor level and side effects.Results
A total of 13 studies with 1196 patients were included in this meta-analysis. The results of this study show that the calcipotriol-acitretin combination therapy could improve the total effective rate when compared with acitretin [RR = 1.25, 95% CI (1.18, 1.33)] or calcipotriol [RR = 1.36, 95% CI (1.20, 1.56)] monotherapy. The combined therapy could decrease the PASI score observably when compared with acitretin monotherapy [SMD = - 2.26, 95% CI (-3.24, -1.28)] or calcipotriol monotherapy [SMD = - 3.79, 95% CI (-5.78, -1.79)]. Calcipotriol-acitretin combination therapy remarkably reduced the levels of TNF-α, IL-23, IL-17, INF-γ and IL-6 in serum, while increasing the levels of IL-4 and IL-10 within the serum, compared to acitretin monotherapy. This combination therapy did not increase the risk of skin irritation & burning pain, dry skin and perioral dermatitis. Notably, the incidence of perioral dermatitis was lower in combination therapy than acitretin monotherapy [P = 0.04, RR = 0.24, 95% CI (0.06, 0.93)].Conclusions
The calcipotriol-acitretin combination therapy could be a safe and effective therapeutic strategy in the treatment of psoriasis. However, the lack of PROSPERO registration and the high heterogeneity in this study limited the conclusion, and more high-quality RCTs were needed for further evaluation.Weiterlesen
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Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood.Objective
To investigated the effectiveness of extracellular vesicles (EVs) derived from MSCs that were genetically modified to overexpress miR-146a, in a mouse model of psoriasis.Methods
To enhance miR-146a expression, MSCs were transfected, and their EVs were subsequently purified. Thirty mice were randomly assigned to three groups and induced with imiquimod cream to develop psoriasis-like skin lesions. The treatment groups included: (1) a control group administered PBS, (2) a group treated with EVs containing a control miRNA (miR-control EVs), and (3) a group receiving EVs enriched with miR-146a (miR-146a-EVs). EVs were administered intravenously and lesions were evaluated. Following intravenous administration of EVs, the severity of skin lesions was assessed. Concentrations of key cytokines, including IFN-γ, IL-17, TNF-α, IL-23, IL-6, IL-1β, TGF-β, IL-10, and IL-4, were quantified in both spleen and skin tissue lysates using ELISA and qRT-PCR techniques.Results
The experimental findings demonstrated that the administration of miR-146a-enriched EVs led to a significant improvement in clinical symptoms. There were substantial reductions observed in combined erythema, scaling, and skin thickness measurements compared to untreated controls. Additionally, levels of proinflammatory cytokines IFN-γ, IL-17, TNF-α, IL-23, IL-6, and IL-1β were significantly downregulated in the miR-146a-EV group, while anti-inflammatory TGF-β, IL-10 and IL-4 were upregulated. The same results were obtained in the spleens of mice.Conclusion
EVs derived from miR-146a-modified MSCs effectively reduced psoriasis-like inflammation by modulating cytokine expression. This novel cell-free therapy holds promise for the treatment of psoriasis.Weiterlesen
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Psoriatic arthritis (PsA) is an immune-inflammatory disease involving skin and synovial-entheseal compartments. The understanding of IL-17 biological function has revolutionized the understanding of PsA pathogenesis and, consequently, its therapeutic approach.Areas covered
In this review article, we have outlined the primary evidence regarding the biological functions of IL-17A in PsA, and summarized data from randomized controlled trials (RCTs) on PsA and psoriasis approved secukinumab, ixekizumab, bimekizumab, brodalumab, and emerging IL-17 inhibitors.Expert opinion
The biologic disease-modifying antirheumatic drugs (bDMARDs), secukinumab, and ixekizumab target interleukin-17A (IL-17A), and bimekizumab, which simultaneously neutralizes IL-17A and IL-17F, have demonstrated efficacy in treating both peripheral and axial articular manifestations of PsA, as well in improving skin involvement, enthesitis and dactylitis. Brodalumab, which inhibits the IL-17 receptor A (IL-17RA), represent an efficacious strategy for psoriasis.Continued research into the role of IL-17s in PsA pathogenesis is crucial for improving our understanding of the disease and developing more effective therapeutic strategies. Further research and advancements in biologic therapies will refine IL-17 inhibitory strategies, potentially improving outcomes for PsA patients, and other immune-mediated diseases.Weiterlesen
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Psoriasis is a chronic immune-mediated skin disease with known physical and mental health comorbidities, such as cardiovascular disease, depression, and anxiety. Psoriasis also has a significant impact on quality of life and sleep due to factors like itch and pain. This study aims to assess the relationship between sleep quality, mental health, and psoriasis, and specifically investigate the impact of poor sleep quality on mental health outcomes within participants with psoriasis.Methods
In this cross-sectional study, we enrolled 556 participants into two cohorts: 487 participants were enrolled into the psoriasis cohort, and 69 were enrolled into the healthy control cohort. The demographics, disease severity, family history, sleep quality (PROMIS 8a, PROMIS 8b, and Insomnia Severity Index), and mental health (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7) of participants were assessed. Descriptive analysis and logistic regression models were employed to examine sleep and mental health, adjusting for potential confounders like demographics and comorbidities.Results
A comparison of patients with psoriasis and healthy controls revealed worsened sleep and mental health outcomes in patients with psoriasis. Among participants with psoriasis, greater sleep impairment (Patient-Reported Outcomes Measurement Information System (PROMIS) 8a), sleep disturbance (PROMIS 8b), and insomnia were significantly associated with anxiety (ORa 1.22; 95% confidence interval (CI) 1.16, 1.30; ORa 1.26; 95% CI 1.16, 1.80; ORa 5.13; 95% CI 2.91, 9.33; respectively) and depression (ORa 1.42; 95% CI 1.32, 1.56; ORa 1.16; 95% CI 1.08, 1.26; ORa 7.04; 95% CI 4.01, 12.77; respectively).Conclusion
These findings underscore the importance of recognizing how psoriasis can impact mental health and sleep. Building a collaborative relationship between patients with psoriasis and their providers is essential to improve overall sleep and life quality.Weiterlesen
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The impact of traditional systemic drugs to treat psoriasis (ciclosporin, methotrexate, and acitretin) in a subsequent response to biologics has not been adequately addressed in the literature. In clinical practice, it is increasingly necessary to initiate, due to concomitant comorbidities, biologics in patients with psoriasis or psoriatic arthritis (PsA) who have not undergone prior treatment with systemics, i.e. full-naive.Objectives and methods
This study analyzed the possible impact of non-biological systemic therapies on the effectiveness and drug survival of first-line biologic drug up to 12 months in bio-naive psoriatic and PsA patients consecutively enrolled from January 2017 to March 2021.Results
Ninety-five patients with severe psoriasis (13.5%) were full-naive. Being full-naive and having or not having undergone methotrexate or cyclosporine therapy did not impact response to subsequent years of biologic therapy. Only acitretin promotes faster response to subsequent biologic drugs with 59.6% and 74.2% of patients achieving Psoriasis Area Severity Index (PASI) 90 at 16 and 28 week, respectively, vs. 50.5% and 65% (p = 0.034 and 0.026). In multivariate analysis, the advantage given by acitretin was lost.Conclusion
Previous systemic therapy in bio-naive patients does not appear to result in a differential response to biologics during the first year of treatment.Weiterlesen
- 187 Aufrufe
Psoriasis is a chronic skin disease affected by genetic and autoimmunity. The traditional Chinese medicine, Compound Qingdai Capsule (CQC), has shown potential benefits in treating psoriasis in clinical settings. Despite its efficacy, the molecular mechanisms underpinning its therapeutic action remain unclear.Purpose
This study aimed to unravel the molecular mechanism of Compound Qingdai Capsule for psoriasis based on the psoriasis pathogenic pathway network, integrating multi-omics analysis, systems pharmacology, machine learning modeling, and animal experimentation.Methods
Psoriasis pathogenic pathway network was constructed through employing bioinformatics analysis and psoriasis-related multi-omics data mining. The ingredients of CQC were detected by UPLC-MS/MS, and target prediction was performed by systems pharmacology. Machine learning, including Lasso regression, Random Forest, and Support Vector Machine (SVM), were utilized to screen core targets of psoriasis. Molecular docking was employed to evaluate the binding affinity between ingredients and core targets. The expression levels of core targets were determined using qRT-PCR and ELISA.Results
Psoriasis-related datasets GSE201827 and GSE174763 were comprehensively analyzed to obtain 635 psoriasis-related genes. These genes were further enriched to elucidate signaling pathways involved, leading to the construction of psoriasis pathogenic pathway network. Utilizing UPLC-MS/MS, 29 main ingredients of CQC were characterized. CQC ingredients-targets network was constructed using these ingredients and their targets. Screening of CQC anti-psoriasis core targets using machine learning algorithm. Molecular docking confirmed good binding affinity between these targets and ingredients. Imiquimod (IMQ) induced psoriasis-like rat validated the anti-psoriasis effect of CQC by alleviating symptoms, reducing spleen and thymus index, and modulating the expressions of core targets at mRNA and protein levels.Conclusion
CQC effectively modulates the expression levels of AURKB, CCNB1, CCNB2, CCNE1, CDK1, and JAK3 through various ingredients, such as astilbin, salvianolic acid A, and engeletin, via multiple pathways, thereby alleviating psoriasis-like symptoms.Weiterlesen
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Research findings show a substantial correlation between Crohn's disease and psoriasis. However, the exact cause or pathogenesis of the concurrent manifestations of these two conditions in the same individuals remains uncertain. This research aimed to scrutinize the important molecules and mechanisms responsible for the concomitance of Crohn's disease and Psoriasis by using quantitative bioinformatics utilizing a publicly available RNA sequencing repository.Methods
The database Gene Expression Omnibus were assessed, specifically for Crohn's disease (GSE95095) and psoriasis (GSE13355). The 'limma' library of the R programming syntax is employed to identify differentially expressed genes. The Search Tool for Interacting Genes dataset was utilized to study the interaction between proteins networks. The Cytoscape software was utilized to efficiently view and analyse these Protein-Protein Interaction networks. The ctoHubba Cytoscape plugin helps in the selection of hub genes. These hub genes have been confirmed using data from GSE102133 for Crohn's disease and GSE14905 for psoriasis. The ROC curves were utilized in this study to assess the diagnostic value of the hub genes. Moreover, new research involving gene-set enriched studies and the study of immunological surveillance associated with these specific genes is attainable.Results
Among the identified common DEGs, 40 genes were downregulated and 37 were upregulated, totaling 77 genes. Crohn's disease and Psoriasis had a higher concentration of pathways associated with inflammation. After validation, functionality of hub genes was confirmed for S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8. The hub genes showed an increase in expression in response to neutrophil infiltration. The expression of S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8 was found to be significantly linked to immune processes such as neutrophil activation, neutrophil chemotaxis, and neutrophil migration associated with Crohn's and Psoriasis disease.Conclusions
This bioinformatics study has elucidated S100A12, CXCL8, IL1RN, S100A9, CXCL10, MMP1, CXCL1, FPR1, CXCR2, and S100A8 as the central genes in the pathogenesis of CD and Psoriasis comorbidity. The significance of neutrophil infiltration in promoting inflammatory and immune-mediated dysfunction seems to be crucial in the etiology of concurrent Crohn's and Psoriasis, offering an avenue for diagnostic and therapeutic methods.Weiterlesen
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Palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition characterized by pustules on the palms and soles. Patients with PPP may be at an increased risk of developing psoriatic arthritis (PsA). The Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire is a tool designed to screen for PsA in at-risk populations. The objective of this study was to identify potential risk factors influencing PASE scores in patients with PPP.Methods
The EPPPIK study was a cross-sectional, multicenter, noninterventional study conducted at 20 sites in Korea, in which patients (≥ 19 years of age) with a confirmed PPP diagnosis were reviewed. In a post hoc analysis of EPPPIK data, PASE outcomes were evaluated for two groups of patients with PPP stratified on the basis of a cutoff score of 37 points.Results
In total, 375 patients with PPP (mean age, 51.3 years; 38.9% male) were included. At enrollment, 175 (46.7%) patients had a PASE score ≥ 37, and 200 (53.3%) patients had a PASE score < 37. Significant differences between the groups were demonstrated for sex, age of menarche, presence of arthritis or psoriatic arthropathy, Physician's Global Assessment score, Palmo-Plantar Pustulosis Area and Severity Index (PPPASI) score, and hand PPPASI score (p ≤ 0.05). Quality-of-life (QoL) measurements and patient-reported outcomes were significantly worse in patients with PASE ≥ 37 (p ≤ 0.05). Multivariable linear regression analysis revealed that a PASE score ≥ 37 was positively associated with female sex (β = 7.19; p < 0.001) and high hand PPPASI score (β = 0.22; p = 0.0243).Conclusions
In patients with PPP, PASE score ≥ 37 correlated with increased presence of any arthritis or psoriatic arthropathy, more severe PPP, worse QoL outcomes, female sex, and higher hand PPPASI scores. Therefore, PASE may serve as a useful tool for initial screening and appropriate treatment selection, management, and ongoing monitoring of patients with PPP.Weiterlesen
- 181 Aufrufe
Psoriasis is a common chronic inflammatory skin disease. Acupoint injection is reported to be used for the treatment of psoriasis, however its mechanism is not yet clear. The study aimed to investigate the efficiency of combined treatment including acupoint injection in the treatment of psoriasis.Patients and methods
Here, we compared the efficacy of multiple immune intervention therapy (MII, acupoint injection with BCG-PSN combined with thymosin enteric-coated tablets, levamisole, intramuscular injection with BCG-PSN) to NB-UVB and acitretin for psoriasis. One thousand two hundred patients with moderate-severe psoriasis vulgaris were randomly treated with MII, NB-UVB or acitretin. For another 53 patients treated with MII, the T cell subsets and TCR repertoire analysis were investigated with sequencing and flow cytometry.Results
The effective rate in MII treated group was similar to acitretin-treated group in 3 months (P > 0.05), though lower than in subjected treated with NB-UVB (P < 0.05). MII treatments maintained a longer remission of both PASI25 and PASI75 in comparison to the treatment with either NB-UVB or acitretin in following 5-year follow-up. Moreover, the relapse rate was lower in MII treatment than in either NB-UVB (P < 0.0001) or acitretin treatment (P < 0.0001), accompanied with longer remission duration (MII vs both NB-UVB and acitretin, P < 0.0001). Meanwhile, MII treatments markedly increased Treg cells (P = 0.04), while decreasing the number of both Th1 (P < 0.001) and Th17 cell (P = 0.01), along with decreased secretion of IFN-γ (P = 0.03) and IL-17 (P = 0.02). Multivariable Cox regression analysis demonstrated that MII significantly reduced psoriasis relapse risk versus NB-UVB (58.7% reduction; HR = 0.413, 95% CI: 0.329-0.517, P < 0.001) and acitretin (65.3% reduction; HR = 0.347, 95% CI: 0.276-0.435, P<0.001).Conclusion
Acupoint injection combined with BCG-PSN, thymosin enteric-coated tablets and levamisole treat psoriasis and prevent relapse of psoriasis, via modulation of Treg/Th1/Th17.Weiterlesen
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To describe the psoriatic phenotype associated with psoriatic arthritis (PsA).Methods
Based on the previously published 4-item Psoriatic Arthritis Uncluttered Screening Evaluation (PURE-4) validation study, this work aims to describe the sociodemographic and clinical characteristics, as well as the PURE-4 questionnaire outcomes, of patients with psoriasis (PsO) who completed the study. It compares those diagnosed with PsA during the study to those with PsO only. The variables compared were age, sex, time since diagnosis of PsO, PsO location, PsO treatment, Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI).Results
The study included 253 patients with PsO, from whom 46 developed PsA (28 [60.9%] male; mean age 48.9 [11.1] years) during the study. At baseline, patients who developed PsA had more involvement of PsO in the neck (13% vs 3.4%, P < 0.01), knees (71.4% vs 50%, P = 0.02), hands (40% vs 17.7%, P < 0.01), and feet (22.9% vs 9.8%, P = 0.03) as well as high-impact areas. PASI (8.7 [SD 5.6] vs 6.8 [SD 5.0], P = 0.03) and DLQI (9.9 [SD 6.9] vs 7.6 [SD 6.7], P = 0.09) values were higher among patients with PsA. Peripheral joint pain with swelling (item 4) was the most prevalent item of PURE-4 among patients with PsA, ranging from 67.6% (vs 47.1%; P = 0.03) in Assessment I to 91.7% (vs 45.4%; P < 0.01) in Assessment II.Conclusion
Greater PsO involvement in neck, knees, hands, and feet as well as in high-impact areas of patients who developed PsA provides additional information on the arthritogenic phenotype of PsO in our study population compared to locations generally linked to arthritis risk, such as the nails or scalp.Weiterlesen
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Psoriasis is a chronic, systemic inflammatory disease with significant physical and psychosocial burden. Advances in understanding the pathogenesis of psoriasis, particularly the role of interleukin (IL)23/Th17 axis, have led to the development of selective drugs targeting these cytokines. Among these, IL23 inhibitors (guselkumab, risankizumab, and tildrakizumab), represent the most recent class of biologic drugs approved for the management of moderate-to-severe plaque psoriasis. Since their approval, real-life data on the use of anti-IL23 have confirmed their high efficacy, durability, and favorable safety profile.Areas covered
This narrative review summarizes real-world data on the effectiveness, also in difficult-to-treat areas, safety, and drug survival of IL23 inhibitors in psoriasis.Expert opinion
Real-world evidence consistently confirms the strong efficacy, favorable safety profile, and long-term treatment durability of IL23 inhibitors across various patient subgroups, including those with comorbidities, prior biologic failures, and the involvement of difficult-to-treat areas. IL23 inhibitors have become key components of the therapeutic arsenal in psoriasis, and their performance in real-world settings continues to support their widespread adoption in clinical practice.Weiterlesen
- 190 Aufrufe
Psoriasis is frequently associated with metabolic syndrome and an increased cardiovascular risk. Tildrakizumab, an IL-23 inhibitor, may affect metabolic parameters in addition to improving skin severity.Aim of the study
To evaluate the impact of increasing tildrakizumab dosage on lipid and glucose levels in psoriasis patients with metabolic syndrome who showed a partial response to the standard 100 mg dose.Materials and methods
Twenty-five patients with psoriasis and metabolic syndrome were enrolled in a 52-week prospective study. After 16 weeks of treatment with 100 mg tildrakizumab, patients with an absolute PASI >2 were switched to 200 mg. Total cholesterol, LDL, and glucose were measured at baseline, week 16, week 40, alongside PASI and DLQI.Results
At baseline, mean total cholesterol, LDL, and glucose were 190.7, 120.1, and 99.4 mg/dL, respectively. The 100 mg dose did not result in significant metabolic changes at week 16. However, switching to 200 mg tildrakizumab led to significant reductions at week 40 in total cholesterol (178.3 mg/dL), LDL (110.1 mg/dL), and glucose (87.2 mg/dL) (all p < 0.05). Significant improvements in PASI (1.2) and DLQI (0.2) were also observed (p < 0.05).Conclusions
Increasing the tildrakizumab dose to 200 mg in partial responders with metabolic syndrome significantly improved both skin severity and metabolic profiles, lowering cholesterol, LDL, and glucose. These findings suggest a possible dose-dependent effect of tildrakizumab on metabolic parameters through enhanced IL-23 inhibition.Weiterlesen
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