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The concept of severity in psoriatic arthritis (PsA) remains inconsistently defined, often conflated with disease activity. This scoping review aimed to explore how severity has been defined in the PsA literature and to identify criteria used to characterize severe disease.Methods
A scoping review was conducted in April 2025 following PRISMA-ScR guidelines. PubMed was searched for English-language articles from the last 25 years, alongside abstracts from major rheumatology conferences. Eligible studies had to explicitly define or discuss PsA severity. Articles focusing solely on activity, isolated disease manifestations, or other conditions were excluded. Data were extracted on the type of article, definitions of severity, and criteria used.Results
Of 4,014 records screened, 32 studies met inclusion criteria. Definitions of severity varied widely and were categorized into imaging (e.g., erosions), clinical (e.g., dactylitis, joint counts), and functional (e.g., HAQ-DI scores) criteria. The most commonly used indicators were structural damage, polyarticular involvement, dactylitis, arthritis mutilans, and validated composite indices such as CPDAI. Only a few studies incorporated functional impairment or patient-reported outcomes. While some guidelines, including GRAPPA and ACR/NPF, proposed multidomain frameworks, a standardized definition remains lacking.Conclusion
The concept of PsA severity has evolved beyond mere disease activity to encompass long-term outcomes, radiographic damage and overall disease burden. However, considerable heterogeneity persists across studies, reflecting the complexity of PsA. A standardized, multidimensional definition of severity, distinct from disease activity, would enhance patient stratification, guide treatment decisions, and support clinical research.Weiterlesen
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Several studies have reported weight gain with tumor necrosis factor inhibitors (TNFi) in psoriatic disease. However, such analyses have not accounted for the natural propensity for weight gain over time. We aimed to investigate whether therapy with TNFi in psoriatic arthritis (PsA) patients is associated with a change in the rate of weight gain post-treatment initiation.Methods
We included patients with at least two weight measurements prior to, and after commencing TNFi and used change point analysis to assess the differences in the rate of weight gain based on the mean slope before and after TNFi initiation, adjusting for clinically relevant variables.Results
Of 234 patients eligible for inclusion, 62.8% were males. At the first clinic visit, the mean (standard deviation) age was 41.8 (12.2) years, while the mean disease duration was 5.1 (6.8) years. The mean weight immediately prior to TNFi use was 83.8 (17.2) kg, while that at the last available visit on TNFi was 86.4 (18.6) kg (p = 0.39), over an average period of 7.9 (5.8) years. The mean values of the pre- and post-TNFi slopes were 0.52 (95% confidence interval [CI] 0.18-0.87) and 0.28 (95% CI - 0.05-0.61), respectively (p = 0.09); thus, there was a trend towards lower rate of weight gain followed the initiation of TNFi therapy.Conclusions
TNFi treatment is not associated with an increase in weight above the expected gain in PsA. Prior trajectory of weight gain with age must be considered while studying the impact of treatment on weight.Key points
• TNFi are commonly used in the management of psoriatic disease and may influence body weight. • TNFi treatment is not associated with a significant increase in body weight when accounting for the trend of weight gain with time. • The trends in weight change may differ between etanercept and monoclonal antibody TNFi agents.Weiterlesen
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To investigate the distribution characteristics of peripheral blood lymphocyte subsets in elderly psoriasis patients and analyze the interactions between immunosenescence and psoriasis and their impact on immune cell subpopulations.Methods
This cross-sectional study enrolled 318 psoriasis patients and 167 healthy controls, stratified by age into elderly (≥ 65 years) and non-elderly (18-64 years) groups. Peripheral blood lymphocyte subsets, including CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and NK cells, were analyzed using four-color flow cytometry. Generalized linear models were employed to analyze associations between PASI scores and lymphocyte subsets, and correlation network analysis was constructed to evaluate interaction patterns among immune cell populations.Results
The elderly psoriasis group demonstrated significantly reduced CD8+ T cell percentage compared to controls (24.52% vs. 28.62%, P < 0.001), accompanied by an elevated Th/Ts ratio (1.57 vs. 1.27, P < 0.001) and significantly increased NK cell percentage and absolute count. Generalized linear modeling revealed a significant negative interaction effect between psoriasis and age on CD8+ T cell percentage (β = -3.979, P = 0.019), while the Th/Ts ratio exhibited a significant positive interaction effect (β = 0.230, P = 0.010). B cell absolute count showed a positive correlation with PASI score (r = 0.180, P = 0.001), with this correlation being more pronounced in elderly patients (r = 0.308, P = 0.014). Network analysis demonstrated reduced connectivity density among immune cell subpopulations in elderly patients.Conclusions
Elderly psoriasis patients exhibit age-related alterations in peripheral blood lymphocyte subset distribution, characterized by decreased CD8+ T cells, elevated Th/Ts ratio, and increased NK cells. B cells may serve as potential biomarkers for assessing disease severity in elderly psoriasis patients.Weiterlesen
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Psoriasis is a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. Objectives:
We aimed to identify circulating metabolites associated with psoriasis, including cutaneous activity, severity, and psoriatic arthritis. Further, we investigated whether the signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). Methods:
We performed a cross-sectional analysis of 270,848 White/European individuals from the UK Biobank (n=253,924) and HUNT (n=16,924). Both cohorts used nuclear magnetic resonance spectroscopy to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. Results:
The metabolomic profile of psoriasis was largely consistent across cohorts. In the model adjusted for age and sex, 116 metabolic measures were associated with psoriasis in both cohorts. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). Despite more substantial metabolic alterations in cutaneous-active psoriasis, GlycA was also elevated in HUNT participants reporting no active psoriasis rash (coefficient [95% CI]: 0.12 [0.04-0.20] in non-cutaneous-active and 0.11 [0.03-0.19] in cutaneous-active psoriasis). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both cohorts, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (coefficient [95% CI]: 0.41 [0.20-0.62] in UK Biobank and 0.47 [0.28-0.67] in HUNT). All IMIDs showed elevated GlycA and reduced albumin, with milder changes in atopic dermatitis. Psoriasis in the HUNT cohort exhibited a distinct lipoprotein profile compared to other IMIDs. Conclusions:
This large-scale, cross-cohort study confirms metabolic alterations in individuals with psoriasis and highlights elevated GlycA levels regardless of cutaneous activity. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis.Weiterlesen
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Psoriatic arthritis (PsA) and juvenile PsA (jPsA) are chronic inflammatory diseases with similar features that differ by age and sequence of symptom onset. PsA and psoriasis (PsO) share comparable pathology across ages, with interleukin (IL)-23 as a key mediator. Prior to the recent US FDA approval of guselkumab for treatment of pediatric plaque PsO and active jPsA, no approved pediatric treatment selectively targeted IL-23 signaling. Guselkumab (a fully human, dual-acting, IL-23p19 subunit inhibitor) was shown to be safe and effective in adult PsO and PsA, with consistent clinical benefits and safety in pediatric PsO. As jPsA shares features, including clinical characteristics and pathogenesis, with PsO and PsA, findings were extrapolated to jPsA using a similar approach previously applied to support ustekinumab and golimumab use in jPsA, which served as precedents for these analyses with guselkumab.Aims
The aim of this study was to demonstrate the similarity of serum guselkumab concentrations, clinical response, and safety among children and adults with PsO and/or PsA in guselkumab randomized controlled trials.Methods
One-year data from participants receiving guselkumab at Week (W)0, W4, then every 8 weeks in VOYAGE 1/2 (adult PsO; N = 1221), DISCOVER-1/-2 (adult PsA; N = 375), and PROTOSTAR (pediatric PsO; N = 92; n = 3 with concurrent jPsA) were included. Serum guselkumab concentrations, Investigator Global Assessment of clear/minimal (IGA 0/1) and Psoriasis Area and Severity Index (PASI) 75/90/100 response rates and safety outcomes were summarized.Results
Serum guselkumab concentrations over 1 year were similar between pediatric (max median: 3.2 µg/mL) and adult PsO (3.7 µg/mL), adult PsO and PsA (4.2 µg/mL), and pediatric PsO and adult PsA. IGA 0/1 response rates at W16 were approximately similar in guselkumab-treated participants with pediatric PsO (66%), adult PsO (84%), and adult PsA (77%). W16 PASI 75/90/100 response rates were comparable across guselkumab-treated participants with pediatric PsO without jPsA (PASI 75: 77%; PASI 90: 56%; PASI 100: 33%), pediatric PsO with jPsA (1 of 2 participants achieved all PASI improvement levels), and adult PsA (77%; 55%; 22%). Guselkumab safety outcomes were similar across ages and diseases.Conclusion
Comparable pharmacokinetic and clinical findings with guselkumab in children with PsO (3 with concurrent jPsA) and adults with PsO and PsA support the extrapolation of efficacy and safety data from adults to children with jPsA, supporting guselkumab use in jPsA.Clinical trials registration
The clinical trials included in this analysis are registered at www.Clinicaltrials
gov with the identifiers: NCT02207231 (VOYAGE 1), NCT02207244 (VOYAGE 2), NCT03162796 (DISCOVER-1), NCT03158285 (DISCOVER-2), and NCT03451851 (PROTOSTAR).Weiterlesen
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The pathogenesis of psoriasis is characterized by dysregulated post-translational modifications, with particular emphasis on fucosylation-a glycosylation process mediated by fucosyltransferases (FUTs). Keratin 17 (K17), overexpressed in psoriatic keratinocytes, drives inflammation and proliferation, but its interplay with fucosylation remains unclear. This study aimed to elucidate the role of fucosylation in psoriasis, specifically focusing on the regulation of K17 stability by FUT11.Methods
To investigate fucosylation dynamics, we employed single-cell RNA sequencing (scRNA-seq) to analyze N-glycan biosynthesis activity in psoriatic versus healthy keratinocytes. Fucosylation levels were assessed in human and murine psoriatic lesions, as well as in cytokine-stimulated keratinocytes, using Aleuria aurantia lectin (AAL). An imiquimod (IMQ)-induced psoriasis-like mouse model and primary keratinocytes treated with psoriasis-associated cytokines (Pso-Mix) (IL-17, TNF-α, IL-1α, OSM and IL-22) were utilized to evaluate the effects of 2-fluorofucose (2-FF) and FUT11 siRNA. We further explored the mechanisms regulating K17 stability through immunoprecipitation, ubiquitination assays, and cycloheximide chase experiments.Results
Our findings revealed that psoriatic keratinocytes exhibited elevated levels of fucosylation, which correlated with upregulation of FUT11. Administration of 2-FF or silencing FUT11 significantly attenuated IMQ-induced inflammation, as evidenced by reductions in epidermal thickness, immune cell infiltration, and the expression of pro-inflammatory mediators such as IL-17A and CCL20. We demonstrated that FUT11 mediates α-1,3-fucosylation of K17, stabilizing it through K63-linked ubiquitination facilitated. Notably, silencing FUT11 disrupted the interaction between ubiquitination and fucosylation, leading to accelerated K17 degradation and a subsequent decrease in keratinocyte proliferation.Conclusions
Our results indicate that FUT11-driven fucosylation is integral to the stabilization of K17 via K63 ubiquitination, thereby perpetuating psoriatic inflammation. Targeting FUT11 or inhibiting fucosylation with 2-FF presents a novel therapeutic strategy for psoriasis management. This study highlights the critical interplay between glycosylation and ubiquitination in the pathophysiology of psoriasis, positioning FUT11 and K17 as pivotal targets for intervention.Weiterlesen
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Psoriasis 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.Purpose
This 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.Methods
Our 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.Results
A 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.Conclusion
Disease 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
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Secukinumab, 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.Methods
In 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).Results
Both 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.Conclusion
Secukinumab treatment in psoriasis is accompanied by HPA axis activation. Further studies are needed to determine the duration, mechanisms, and magnitude of this activation.Weiterlesen
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As 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.Methods
Relevant 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.Results
Seven 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.Conclusion
All 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 number
CRD42023476983.Weiterlesen
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Inflammatory 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.Methods
Our 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.Results
The 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.Conclusion
This 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
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