Neue Studien: Europe PMC

RETRACTION: Mendelian Randomization Analysis of Psoriasis and Psoriatic Arthritis Associated With Risks of Ulcerative Colitis.

Tue, 14 Oct 2025 14:46:53 +0000

No abstract supplied.

Cardiovascular Risk in Autoimmune Diseases: Mechanisms, Management, and Emerging Evidence

Tue, 14 Oct 2025 14:46:53 +0000

No abstract supplied.

What drives patient cost variability in psoriasis care: a single centre study.

Tue, 14 Oct 2025 14:32:50 +0000

Background

Psoriasis a chronic inflammatory skin disease, poses a substantial economic burden on healthcare systems globally. This study examines psoriasis consultations from the provider's perspective within a dermatology department, aiming to generate detailed cost data to support value-based care. Specifically, it investigates the drivers of consultation-level cost variability, explores opportunities for efficiency, and also estimates one-year treatment costs to inform the development of bundled payment models. The goal is to highlight the importance of patient cost transparency and improving cost structures in chronic disease settings.

Methods

Using Time-Driven Activity-Based Costing (TD-ABC), treatment costs associated with nurses, doctors, and total visits for 127 patients with mild and moderate forms of psoriasis were measured. Financial data was collected in collaboration with the hospital's financial department. During consultations, nurses and physicians recorded time and patient-related information. Additional or missing details were retrieved from patient medical files. Descriptive analyses assessed mean costs and variability by patient and disease characteristics.

Independent variables

therapy type, patient status (new vs. returning), comorbidities, and treatment changes, were stratified to compare cost differences across groups.

Results

Mean consultation costs were €55, with a minimum and maximum of €25 and €110. New patients incurred 40% higher costs than returning ones, mainly due to longer interactions with nurses and physicians. Key cost drivers for a total consultation included patient status, personality traits, nurse experience, and therapy switches. Physician consultations were particularly impacted by treatment changes and patient engagement levels. Annual treatment costs varied substantially by medication type: topical treatments averaged €325 per year, systemic treatments €1,353, and biological therapies €11,920, highlighting the significant impact of medication choice on overall expenses.

Conclusions

This study highlighted substantial variability in consultation and yearly treatment costs for psoriasis patients. These findings emphasized the critical need for detailed cost data to optimise departmental workflows, support efficient resource allocation, and inform the design of equitable bundled payment models. Improving cost transparency was shown to strengthen clinical and financial decision-making. Future research was recommended to explore the cost implications of comorbidities and to extend benchmarking efforts across dermatology settings to guide system-wide improvements in care delivery and sustainability.

Dual-responsive gelatin-based amphiphilic celastrol prodrug polymer nanoassemblies for psoriasis treatment.

Tue, 14 Oct 2025 14:32:50 +0000

Celastrol(CE) has been investigated for its prophylactic and anti-inflammatory effects in various inflammatory and autoimmune diseases like psoriasis. However, poor water solubility, low bioavailability, and high toxicity, have limited its application The objective of this study is to design and synthesize a gelatin-based CE prodrug polymer which can self-assemble into nanoparticles, encapsulating CE to improve its aqueous solubility. Two gelatin derivatives with opposite charges were synthesized through a condensation reaction. CE prodrug nanoparticles were formed by coupling CE to these two gelatin derivatives using dynamic chemical bonding: C-S bonds and borate bonds. The resulting nanoparticles(G-C-G) had an average particle size of approximately 147.15 ± 8.25 nm, and a drug loading capacity (DL) of 1.52 ± 0.25%. The transdermal penetration of nanoparticles (G-C-G) was found to be improved compared to free CE in vitro. In a mouse model of psoriasis, nanoparticles G-C-G resulted in a reduction of erythema, scaly epidermal symptoms, spleen weight, and cytokine levels, including IL-17 and IL-23, indicating high therapeutic potential for psoriasis. In conclusion, CE prodrug nanoparticles (G-C-G) increase the water solubility and skin permeability of free CE, making it a potential therapeutic agent for psoriasis.

Serum SCCA as a biomarker for assessing severity and monitoring treatment response in psoriasis.

Tue, 14 Oct 2025 14:32:50 +0000

Background

While clinical examination remains the diagnostic cornerstone for psoriasis, there is a relative lack of objective, quantitative biomarkers to complement clinical assessment for tracking disease severity and monitoring therapeutic response. We evaluated serum SCCA's utility in identifying psoriasis and assessing its severity across demographic (gender, age) and clinical (comorbidity) subgroups, and its association with therapeutic responses.

Methods

A total of 181 adult (≥18 years old) patients with newly diagnosed psoriasis were included in the disease group; 385 patients with other skin-related diseases and 658 healthy adults were included as controls. Patients diagnosed with tumors or renal failure were excluded. Serum SCCA was determined using Roche Cobas e 801 analyzer (Roche, Basel, Switzerland). Dynamic analysis was performed to evaluate the significance of serum SCCA in monitoring psoriasis treatment response.

Results

Serum SCCA levels in psoriasis patients were mainly affected by gender and concomitant diseases. Notably, SCCA demonstrated high diagnostic accuracy (AUC: 0.89-0.90) in patients with comorbidities, with sex-specific cutoffs. The cutoff value of serum SCCA for identifying severe psoriasis was 2.64 ng/mL with an AUC greater than 0.9 and an NPV over 95 %. Serum SCCA levels were significantly correlated with the psoriasis area and severity index (PASI) and body surface area (BSA) both before and after treatment. The median decrease rate of serum SCCA was close to 50 % at >5 days post-treatment and 60 % at >10 days post-treatment.

Conclusions

Serum SCCA shows promise as a reliable, complementary biomarker for the severity assessment and treatment monitoring of psoriasis. Its application for identification purposes should be stratified by sex and comorbidities.

Response to Chen et al.'s "Risk of major adverse cardiovascular events and venous thromboembolic events between patients with psoriasis or psoriatic arthritis on tumor necrosis factor inhibitors, interleukin 17 inhibitors, interleukin 12/23 inhibitors, an

Tue, 14 Oct 2025 14:32:50 +0000

No abstract supplied.

Psoriatic Arthritis Linked to Pembrolizumab in a Lung Cancer Patient: From Oncologist to Rheumatologist

Tue, 14 Oct 2025 14:32:50 +0000

No abstract supplied.

Cuproptosis Facilitates Chronic Skin Inflammation by Regulating the α-Ketoglutarate/H3K4me3/Ferritin Heavy Chain 1 Signaling Pathway-Mediated Ferroptosis.

Tue, 14 Oct 2025 14:32:50 +0000

Dysregulated copper homeostasis is implicated in inflammatory skin diseases such as psoriasis and atopic dermatitis (AD), but the role of cuproptosis remains poorly defined. This study aimed to elucidate the role and mechanism of cuproptosis in inflammatory skin diseases. Transcriptome analysis of patient lesions revealed significant alterations in cuproptosis-related genes correlating with disease-specific pathological features. These cuproptosis-related gene expression signatures demonstrated strong clinical relevance to therapeutic efficacy in both psoriasis and AD cohorts. Functional validation using disease models showed that pharmacologically inhibiting cuproptosis with the copper chelator tetrathiomolybdate (TTM), or genetically knocking down the copper importer SLC31A1, effectively alleviated chronic skin inflammation and hallmark pathological changes induced by imiquimod (IMQ) or calcipotriol (MC903). Mechanistically, we uncovered that SLC31A1-mediated cuproptosis promotes intracellular α-ketoglutarate (α-KG) accumulation, driving activation of the lysine demethylase KDM5B. Activated KDM5B specifically demethylates H3K4me3 marks at the promoter of the ferroptosis regulator ferritin heavy chain 1 (FTH1), suppressing its transcription and consequently sensitizing keratinocytes to ferroptotic cell death, thereby amplifying inflammatory tissue damage. Our findings establish a fundamental pathogenic SLC31A1/KDM5B/FTH1 molecular axis linking dysregulated copper metabolism and cuproptosis to ferroptosis execution in psoriasis and AD, providing significant mechanistic insights and pinpointing promising therapeutic targets for these refractory skin disorders.

A Trial of Coach-Supported, Smartphone-Delivered Cognitive Behavioral Therapy for Psoriasis With Comorbid Depression

Tue, 14 Oct 2025 14:32:50 +0000

No abstract supplied.

Psoriasis and the risk of 26 cancers: pooled population-based cohort studies from Denmark, England, Israel, and Taiwan.

Tue, 14 Oct 2025 14:32:50 +0000

Background

Psoriasis is a chronic inflammatory skin disease, and the risk of developing cancer has been postulated due to the presence of several plausible underlying mechanisms. Understanding the association between psoriasis and cancer is imperative to the provision of optimal psoriasis care.

Objectives

To examine the risk of developing cancer in individuals with psoriasis.

Methods

Population-based cohort studies were conducted in Denmark, England, Israel, and Taiwan through the use of linked electronic health records. Individuals aged at least 18 years of age with a diagnosis of psoriasis in the country-specific study period were matched to up to 6 comparators with no record of psoriasis prior to index date. Country-specific hazard ratios for the risk of cancer development overall and for 26 site-specific cancers between individuals with and without psoriasis were calculated through Cox regression. Country-specific estimates were pooled using random effects modelling.

Results

We included 702,022 individuals with psoriasis and 4,185,342 matched comparators. In models implicitly controlled for age, sex and calendar time by matching, there was a small association between psoriasis and cancer overall (pooled HR [pHR]:1.08;95%CI, 1.04-1.13; I2= 92.4%). Adjustment for potential confounding factors resulted in a slight attenuation of risk (pHR:1.05; 95%CI, 1.01-1.09; I2=81.2%). When restricted to those with moderate-to-severe psoriasis, the risk of cancer overall was slightly higher (pHR:1.16;95%CI, 1.04-1.28; I2=92.8%) and confounder adjusted models (pHR: 1.09;95%CI, 1.03-1.15; I2=60.6%). Associations with psoriasis were present for oral cavity (pHR: 1.29; 95%CI, 1.12-1.47; I2=55.4%), pharynx (pHR:1.30;95%CI, 1.07-1.58; I2=58.4%), oesophagus (pHR:1.17;95%CI, 1.03-1.33; I2=56.6%), liver (pHR:1.53;95%CI, 1.33-1.77; I2=75.1%), pancreas (pHR:1.09;95%CI, 1.02-1.17; I2=0.0%), kidney (pHR:1.19;95%CI, 1.11-1.27; I2=0.0%), bladder (pHR: 1.13; 95%CI, 1.06-1.20; I2=28.7%), and keratinocyte cancers (pHR:1.37;95%CI, 1.16-1.63; I2=97.5%), Hodgkin lymphoma (pHR:1.56;95%CI, 1.16-2.11; I2=69.7%), non-Hodgkin lymphoma (pHR:1.16;95%CI, 1.07-1.26; I2=35.5%) and leukaemia (pHR:1.18; 95%CI, 1.08-1.29; I2=41.9%). Site-specific associations generally persisted, with slight risk exacerbations and additional associations for lung and ovarian cancers, when limited to people with moderate-to-severe psoriasis.

Conclusion

Psoriasis was associated with an increased risk of developing 14 of 26 investigated site-specific cancers, including cancers with poor prognosis, such as liver, lung, and oesophageal cancer. Our findings can be used to reinforce cancer prevention strategies in psoriasis care.

A Trial of Coach-Supported, Smartphone-Delivered Cognitive Behavioral Therapy for Psoriasis With Comorbid Depression.

Tue, 14 Oct 2025 14:32:50 +0000

Background

Psoriasis is associated with increased risk of depression. Although cognitive behavioral therapy (CBT) is an evidence-based treatment, access remains limited.

Objectives

To evaluate the feasibility, acceptability, and preliminary efficacy of a smartphone-delivered, coach-led CBT program for depression among individuals with psoriasis.

Methods

This single-arm, 8-week pilot study (Mindset trial, NCT06216691) enrolled adults with psoriasis and at least mild depressive symptoms (PHQ-9 ≥5). Participants engaged in a smartphone-based CBT program guided by bachelor's-level lay coaches. Primary outcomes were feasibility as evaluated by module completion and acceptability as evaluated by the Client Satisfaction Questionnaire-8 (CSQ-8]) and User Version of the Mobile Application Rating Scale (uMARS). Secondary outcomes included changes in the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Appearance Anxiety Inventory, Skindex-16, and Psoriasis Symptom Inventory.

Results

Of 30 participants, 63.3% completed ≥4/8 modules and 43.3% completed ≥6/8 modules. Mean CSQ-8 and uMARS scores were 27.2 (SD 4.5) and 4.0 (SD 0.7), respectively, supporting high satisfaction. Statistically and clinically significant improvements were observed in PHQ-9 (mean change -4.4; Cohen's d = 0.92), GAD-7 (-2.8; d = 0.63), and Skindex-16 symptoms (5.0; d = 0.78), emotions (10.0; d = 0.95), and functioning (6.4; Cohen's d = 0.71) subscales as well as the Psoriasis Symptom Inventory (3.1; d = 0.43).

Conclusions

This study supports the feasibility, acceptability, and preliminary efficacy of smartphone-delivered CBT for individuals with psoriasis and depressive symptoms. Given the scalability of this model, future randomized trials are warranted to assess broader effectiveness in dermatology care settings.

Toward precision in psoriatic arthritis: addressing the challenge of difficult-to-treat disease.

Tue, 14 Oct 2025 14:32:50 +0000

Introduction

Difficult-to-treat psoriatic arthritis (D2T-PsA) is increasingly recognized as a complex clinical entity characterized by persistent disease burden despite multiple targeted therapies. Its identification is essential to improve patient outcomes and to guide the development of new therapeutic strategies.

Areas covered

In this perspective article, we discuss the evolving concept of D2T-PsA, including its epidemiology, clinical characterization, and underlying pathophysiological mechanisms. We highlight the role of gender differences, psychosocial comorbidities, and central sensitization in shaping disease persistence and patient-reported impact. We also examine the limitations of current disease activity indices (DAPSA, PsAID, PASDAS) in capturing heterogeneity and the need for multidimensional frameworks. A structured literature search was conducted in PubMed/MEDLINE and Scopus databases (January 2020-June 2025), restricted to English-language publications, using combinations of the terms psoriatic arthritis, difficult-to-treat, refractory, and difficult-to-manage. Additional references were identified from conference abstracts and relevant bibliographies.

Expert opinion

Recognizing D2T-PsA as a distinct, multifactorial entity is critical to advancing personalized medicine. Future directions will involve harmonizing EULAR and GRAPPA frameworks, integrating biomarker discovery, digital tools, and adaptive trial designs, and embedding patient perspectives. This multidimensional approach is expected to transform treatment from empirical cycling toward precision care in psoriatic arthritis.

Efficacy and safety of gut microbiota-targeted therapy in patients with psoriasis: a systematic review and meta-analysis of randomized controlled trials.

Fri, 10 Oct 2025 06:15:28 +0000

No abstract supplied.

Preterm birth in women with psoriatic arthritis: what are the risks and risk factors? A collaborative cohort study from Sweden, Denmark and Norway.

Fri, 10 Oct 2025 06:15:28 +0000

Objective

To estimate risk and to identify risk factors for preterm birth in pregnant women with psoriatic arthritis (PsA) in relation to maternal characteristics, treatment and disease activity, both before and during pregnancy.

Methods

We linked clinical rheumatology registers to medical birth registers in Sweden, Denmark and Norway and identified PsA pregnancies and control pregnancies 2006-2021, matched 1:10 on age, parity, country and birth year. Adjusted ORs (aORs) for preterm birth in PsA pregnancies vs control pregnancies were calculated overall and stratified by maternal characteristics, antirheumatic treatment and disease load (9 months before and during pregnancy).

Results

We observed 54 preterm births among 688 PsA pregnancies (7.8%) versus 312 among 6880 control pregnancies (4.5%); aOR, 95% CI: 1.80, 1.29 to 2.51. The risk estimate was largely unaffected by parity, smoking and body mass index. PsA pregnancies exposed to a combination of biologic and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and/or glucocorticoids during pregnancy had a markedly increased risk of preterm birth compared with control pregnancies (4.44, 2.07 to 9.50), whereas exposure to biological DMARD (bDMARD) monotherapy (primarily tumour necrosis factor inhibitors) had not (0.73, 0.22 to 2.42). High disease load before pregnancy was associated with increased risk. The proportion of preterm birth was higher in those stopping bDMARD during the first trimester (21%) opposed to those continuing past the first trimester (10%) based on few events.

Conclusion

We identified an 80% increased risk of preterm birth in PsA pregnancies compared with control pregnancies. Antirheumatic combination therapy during and high disease load before pregnancy constituted risk factors. Discontinuing bDMARD treatment in early pregnancy further increased the risk. Our findings support that a subgroup of PsA pregnancies should be considered high-risk pregnancies.

Cost-effectiveness of deucravacitinib versus apremilast of moderate-to-severe plaque psoriasis in China.

Fri, 10 Oct 2025 06:15:28 +0000

Objectives

The study aimed to assess the cost-effectiveness of deucravacitinib versus apremilast for treating moderate-to-severe plaque psoriasis from the Chinese healthcare system's perspective.

Methods

The treatment efficacy of deucravacitinib was compared with apremilast using response rates derived from the head-to-head phase 3 clinical trials, POETYK PSO-1 and PSO-2. A decision-tree (first 24-week)/ Markov model (later period) was constructed to estimate the incremental cost per quality-adjusted life-year (QALY) gained over a lifetime horizon. The efficacy inputs were based on randomized controlled trials, while adverse event rates, discontinuation probabilities, costs, and utility data were obtained from relevant literature and Chinese sources. A 5% annual discount rate was used for the analysis of outcomes and costs. Model outcomes were characterized by quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probability sensitivity analysis (PSA) were performed to examine the robustness of the results.

Results

According to the assumed lifetime horizon and model, the ICER of deucravacitinib 6 mg once daily compared with apremilast 30 mg twice daily was 140,047 CNY per QALY. Deucravacitinib was more cost-effective than apremilast at the willingness-to-pay (WTP) threshold of 287,247 CNY per QALY. In the One-way sensitivity analysis, the cost of deucravacitinib was identified as the parameter exerting the greatest impact on the base-case results. The results of PSA showed the probability of deucravacitinib being cost-effective was 99.4%.

Conclusion

At the WTP threshold of 287,247 CNY, deucravacitinib 6 mg once daily was a cost-effective treatment strategy for moderate-to-severe plaque psoriasis compared with apremilast 30 mg twice daily from the Chinese healthcare system perspective over a lifetime horizon.

Psoriasis Increases the Risk of ANCA Associated Vasculitis: Insights from A Propensity Score-Matched Study.

Fri, 10 Oct 2025 06:15:28 +0000

Purpose

This study aimed to investigate the risk of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) among patients with psoriasis in a large population.

Patients and methods

In this population-based study using the collaborative electronic health record research network, the risk of developing AAVs (ie, eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA)) was analyzed in a cohort of patients diagnosed with psoriasis between 2006 and 2024. Non-psoriasis controls were selected in a 1:1 ratio using propensity score matching. Patients who were diagnosed with AAVs before the index date were excluded. Univariate Cox proportional hazard model and subgroup analyses were used to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for developing AAVs. The Kaplan-Meier method was used to plot the cumulative incidence curves. The risk of AAVs in psoriatic patients treated with biological agents was explored.

Results

After matching, 436,201 patients were included in each cohort. There were 281 incident cases of AAV during follow-up in the psoriasis cohort and 122 incident cases of AAV in the non-psoriasis cohort. The risk of developing AAVs in the psoriasis cohort was significantly higher than in the non-psoriasis cohort (HRs (95% CI) for AAVs, EGPA, and GPA were 2.01 (1.63 to 2.49), 1.84 (1.11 to 3.06), and 2.11 (1.65 to 2.71), respectively. Compared with psoriasis patients who did not receive biologics, those treated with biologics showed no statistically significant increase in AAVs risk (HR 1.31, 95% CI 0.65 to 2.66).

Conclusion

Patients with psoriasis have a higher risk of AAVs development. Treatment with biologic agents is not associated with an elevated risk of AAVs.

Serum SCCA as a biomarker for assessing severity and monitoring treatment response in psoriasis.

Fri, 10 Oct 2025 06:15:28 +0000

Background

Methods

A total of 181 adult (≥18 years old) patients with newly diagnosed psoriasis were included in the disease group; 385 patients with other skin-related diseases and 658 healthy adults were included as controls. Patients diagnosed with tumors or renal failure were excluded. Serum SCCA was determined using Roche Cobas e 801 analyzer (Roche, Basel, Switzerland). Dynamic analysis was performed to evaluate the significance of serum SCCA in monitoring psoriasis treatment response.

Results

Serum SCCA levels in psoriasis patients were mainly affected by gender and concomitant diseases. Notably, SCCA demonstrated high diagnostic accuracy (AUC: 0.89-0.90) in patients with comorbidities, with sex-specific cutoffs. The cutoff value of serum SCCA for identifying severe psoriasis was 2.64 ng/mL with an AUC greater than 0.9 and an NPV over 95 %. Serum SCCA levels were significantly correlated with the psoriasis area and severity index (PASI) and body surface area (BSA) both before and after treatment. The median decrease rate of serum SCCA was close to 50 % at >5 days post-treatment and 60 % at >10 days post-treatment.

Conclusions

Bimekizumab Efficacy in Psoriasis by Subgroups: Post Hoc Analysis of Phase 3/3b Clinical Trials.

Fri, 10 Oct 2025 06:15:28 +0000

Introduction

Patient demographics, disease characteristics, and treatment history can impact the efficacy of biologic treatments in patients with psoriasis. Understanding the efficacy of biologics, such as bimekizumab, across diverse patient subgroups is important for optimising treatment outcomes. Here, we assess whether high overall clinical responses observed in bimekizumab-treated patients with moderate to severe plaque psoriasis are consistent across subgroups, both versus comparators and with long-term treatment.

Methods

Data were analysed post hoc from the BE SURE, BE VIVID, and BE READY phase 3 trials, their open-label extension (OLE) BE BRIGHT, and the BE RADIANT phase 3b trial. Patients received either bimekizumab or adalimumab to week 24 (BE SURE), bimekizumab or ustekinumab to week 52 (BE VIVID), and bimekizumab or secukinumab to week 48 (BE RADIANT). In the 3-year pooled analysis (all trials), included patients received bimekizumab continuously from baseline into the OLE. Subgroups of patients with moderate to severe plaque psoriasis were defined by age, sex, weight, disease duration, disease severity, nail involvement (modified Nail Psoriasis Severity Index > 0), and prior biologic exposure, at baseline. The proportions of patients achieving complete skin clearance (PASI 100; 100% improvement from baseline in Psoriasis Area and Severity Index) in each subgroup are reported alongside 95% confidence intervals (CI). Modified non-responder imputation (mNRI) was used for missing data.

Results

Following comparator-controlled periods, the proportion of bimekizumab-treated patients who achieved PASI 100 was consistent across subgroups and numerically greater versus patients who received adalimumab (to week 24), ustekinumab (to week 52), and secukinumab (to week 48) in all subgroups. Among patients who received bimekizumab continuously for 3 years (N = 1107), PASI 100 response rates remained consistent across age (68.6% [40 to < 65 years]-73.7% [≥ 65 years]), sex (69.6% [male]-71.4% [female]), weight (63.4% [≥ 103.9 kg]-75.5% [< 74.3 kg]), disease duration (65.5% [≤ 5 years]-71.1% [> 20 years]), disease severity (67.7% [PASI 12 to < 15]-71.1% [PASI ≥ 20]), nail involvement (69.1% [yes]/71.3% [no]), and prior biologic exposure (71.7% [yes]/69.1% [no]; prior anti-TNF exposure 67.6% [yes]/70.6% [no]) subgroups; 95% CIs overlapped in all instances, indicating no meaningful differences between subgroups.

Conclusion

Bimekizumab demonstrated consistently high long-term efficacy in patients with psoriasis across diverse subgroups. Higher rates of PASI 100 were achieved with bimekizumab versus adalimumab, ustekinumab, and secukinumab, across all subgroups. These results highlight bimekizumab as an effective treatment for a broad range of people living with psoriasis.

Trial registration

NCT03412747, NCT03370133, NCT03410992, NCT03598790, NCT03536884.

Interleukin-1 Receptor Antagonist as a Potential Mediator Linking Psoriasis and Non-Alcoholic Fatty Liver Disease: Insights From Mendelian Randomization and Experimental Evidence.

Fri, 10 Oct 2025 06:15:28 +0000

Background

Epidemiological studies have revealed a close association between psoriasis and non-alcoholic fatty liver disease (NAFLD), but the causal relationship and underlying mechanisms remain unclear.

Materials and methods

In this study, we used genome-wide association study (GWAS) data from the MRC Integrative Epidemiology Unit (MRC-IEU) to investigate the causal relationship between psoriasis and NAFLD, as well as potential mediators. Two-sample and two-step MR analyses were conducted, followed by bulk and single-cell transcriptomic analyses to validate our MR findings. In vivo validation was performed using Enzyme-Linked Immunosorbent Assay (Sample of patients (n=10)), immunohistochemistry, and liver bulk transcriptomic analysis.

Results

The two-sample MR analysis revealed that genetically predicted psoriasis significantly increased the risk of NAFLD (OR = 1.07, 95% CI = 1.03-1.12, p = 0.001). Mediation analysis suggested that psoriasis was associated with elevated plasma Interleukin-1 receptor antagonist protein (IL-1RA) levels (OR = 1.02, 95% CI = 1.00-1.05, p = 0.031), which in turn raised the risk of NAFLD (OR = 1.15, 95% CI = 1.04-1.27, p = 0.006). In vivo experiments demonstrated elevated IL-1RA levels in the skin and plasma of psoriasis patients. Similarly, imiquimod (IMQ)-induced psoriasis mouse models exhibited increased IL-1RA levels in plasma and liver, accompanied by liver inflammation. MR and colocalization analysis indicated a positive correlation between IL-1RA, apolipoprotein B, and cholesterol.

Conclusion

Our study demonstrates that genetically predicted psoriasis increases the risk of NAFLD, and plasma IL-1RA may serve as a potential mediator between psoriasis and NAFLD.

Psoriasis and phenotypic age acceleration in relation to all-cause and cardiovascular disease mortality risks in US adults.

Fri, 10 Oct 2025 06:15:28 +0000

Background

Psoriasis is a chronic, immune-mediated inflammatory dermatosis associated with an elevated risk of cardiovascular disease (CVD) due to systemic inflammation and metabolic dysregulation. Phenotypic age acceleration (PhenoAge-accel) quantifies accelerated biological aging by comparing an individual's predicted 'phenotypic age' (based on immune/inflammatory markers and chronological age) to their actual age. Notably, both the onset and progression of psoriasis exhibit strong associations with biological aging process. The aim of this study was to investigate their combined effect on the risk of all-cause and CVD mortality.

Methods

This study included 11,443 participants from the National Health and Nutrition Examination Survey (NHANES) conducted during 2003-2006 and 2009-2010. Weighted multivariable logistic regression models were used to evaluate the association between PhenoAge-accel and psoriasis risk. PhenoAge-accel ≥ 0 was defined as PhenoAge-accel+. Furthermore, participants were stratified into four groups: psoriasis-/PhenoAge-accel-, psoriasis+/PhenoAge-accel-, psoriasis-/PhenoAge-accel+, and psoriasis+/PhenoAge-accel+. The Cox proportional hazards models were employed to investigate the joint effects of psoriasis and PhenoAge-accel on all-cause and CVD mortality risk.

Results

At baseline, 312 participants were diagnosed with psoriasis. After adjusting for covariates, compared to those with PhenoAge-accel < 0, the odds ratios (95% CI) for psoriasis in the PhenoAge-accel ≥ 0 group was 1.83 (1.36-2.45). During a median follow-up of 10.91 years (interquartile range: 9.83-14.75), 1059 deaths event occurred, including 306 caused by CVD. In the multivariable-adjusted model, compared with the reference group, the hazard ratios and 95% CIs for all-cause mortality in the psoriasis-/PhenoAge-accel+, psoriasis+/PhenoAge-accel-, and psoriasis+/PhenoAge-accel+ groups were 1.80 (1.54-2.10), 0.96 (0.56-1.65), and 2.70 (1.66-4.39), respectively. A similar trend was observed for CVD mortality.

Conclusions

PhenoAge-accel is positively associated with psoriasis risk. Furthermore, the coexistence of psoriasis and PhenoAge-accel are significantly associated with an increased risk of all-cause and CVD mortality.

Overexpression of miR-718 in Keratinocytes Affects the Psoriatic Inflammation via Targeting STAT1: In Vitro and In Vivo Evidence.

Fri, 10 Oct 2025 06:15:28 +0000

Psoriasis is a complex inflammatory autoimmune skin illness that causes epidermal keratinocyte hyperproliferation and dedifferentiation. In a previous study we did in the lab, we found that treating human keratinocytes (HaCaT) with PUVA increased the expression of hsa-miR-718 compared to control. In this study, an imiquimod (IMQ)-induced mouse model and HaCaT were used to look at how overexpressing miR-718 could help treat psoriasis and its causes. To gain more understanding, the in vivo study used the JAK1/3 inhibitor tofacitinib. We observed that miR-718 overexpression leads to the inhibition of JAK-STAT signalling, as evidenced by the reduced expression of STAT1, JAK proteins, and their phosphorylated forms, both in vitro and in vivo. Luciferase assay demonstrated the direct inhibition of STAT1 due to miR-718 overexpression. Additionally, in vitro experiments showed downregulation of STAT2 and STAT3. Inhibition of basal miR-718 in HaCaT overactivates JAK-STAT signalling proteins. In psoriatic mice, ectopic miR-718 reduces NF-kB, a key mediator of inflammation. IHC shows lower acanthosis and parakeratosis in IMQ-induced psoriatic mice. In the skin of mice that had been miR-718 transfected, there was less VEGF, MMP7 and MMP9. Understanding how miR-718 improves psoriasis not only provides new information but also inspires hope for its potential use as a psoriasis treatment.

SLPI controls neutrophil migration abilities and impacts neutrophil skin infiltration in experimental psoriasis

Fri, 10 Oct 2025 06:15:28 +0000

Skin infiltration by neutrophils is a hallmark of the chronic inflammatory skin disease psoriasis, yet the mechanisms underlying neutrophil recruitment and positioning in chronically inflamed skin remain poorly understood. In this study, we demonstrate the significant impact of a total genetic deficiency of secretory leukocyte protease inhibitor (SLPI) on neutrophil migration in mouse skin. Without SLPI, neutrophils displayed an unconventional migratory pattern, characterized by altered interactions with vessel walls and reduced efficiency in extravasating from blood vessels into skin tissue during the early stages of experimental psoriasis. This was associated with changes in tissue motility, positioning neutrophils farther from the skin entry vessels and closer to the skin surface. Neutrophil diapedesis was partially dependent on SLPI within the neutrophils themselves. The impact of SLPI on neutrophil movement was further supported by the increased migration of human neutrophils in the presence of neutrophil-penetrant recombinant SLPI. Additionally, our data suggest that neutrophils with varying capacities for vessel wall interaction are released from the bone marrow into circulation in an SLPI-dependent manner. These findings establish a role for SLPI in regulating the spatiotemporal infiltration of neutrophils into the skin in psoriasis, highlighting its relevance to psoriasis pathophysiology.

G-CSF Mediates Increased Renal Neutrophils and Kidney Damage in a Psoriasis Mouse Model.

Thu, 04 Sep 2025 18:54:24 +0000

Psoriasis is an autoimmune skin disease associated with increased incidence and severity of chronic kidney disease and hypertension. The mechanisms linking psoriasis skin inflammation with these comorbidities remain unclear. We used flow cytometry, radiotelemetric blood pressure measurements, and histological and ELISA-based assessments of renal damage in mice with experimental psoriasis induced by keratinocyte-specific overexpression of Tie2 (KC-Tie2) and their littermate controls. Compared with littermate controls, KC-Tie2 mice with chronic skin inflammation developed albuminuria, histological evidence of glomerulosclerosis, and elevated blood pressure. KC-Tie2 mice had a selective and marked increase in circulating and renal neutrophils, along with increased neutrophil extracellular trap formation in the kidneys by flow cytometry. KC-Tie2 mice also exhibited increased bone marrow granulopoiesis along with increases in cutaneous and systemic G-CSF (granulocyte colony-stimulating factor), the primary mediator of granulopoiesis. Finally, neutralization of G-CSF decreased renal neutrophils and kidney damage in KC-Tie2 mice. Our findings demonstrate G-CSF-dependent increases in renal neutrophil accumulation and renal damage in a mouse model of psoriasis. Results suggest a novel link between chronic psoriasiform skin inflammation and renal damage via G-CSF-mediated granulopoiesis, providing new insight into interorgan communication in psoriasis and a potential new therapeutic target for the treatment of psoriasis-related renal dysfunction.

Spleen granulopoiesis in psoriasis immune microenvironment aggravates psoriasis via IL-6/P-STAT3 signaling.

Thu, 04 Sep 2025 18:54:24 +0000

Background

Psoriasis is an immune-mediated chronic inflammatory condition characterized by significant neutrophil infiltration in the skin. Given that the spleen is the largest peripheral immune organ in the body, it is important to investigate whether it has any impact on skin inflammation in psoriasis.

Methods

To investigate this mechanism, a psoriatic mouse model was established by IMQ application. Flow cytometry and immunohistochemistry analyses were performed to determine the percentage of various immune cells in the spleen. The role of neutrophils was specifically assessed using the anti-Gr-1 antibody. Splenic granulopoiesis was evaluated using EdU labeling. To understand the spleen's role in skin inflammation, splenectomy was performed on the experimental mice. IL-6 levels were measured by ELISA, and P-STAT3 in neutrophils was detected via immunofluorescence. Further examination of IL-6's effects on neutrophil formation involved treating mice with IL-6 antibody. The severity of psoriasis was evaluated through histological staining and PASI scoring.

Results

Our study revealed that the spleens of psoriatic mice were enlarged compared to those of vehicle mice. Among immune cell populations, neutrophils showed the most significant changes, with marked increases in both spleen and skin of psoriatic mice and patients, contributing to disease progression. Post-splenectomy, neutrophil infiltration in the skin was reduced by approximately 60% in psoriatic mice. This indicates that the neutrophils in the skin were primarily derived from the spleen. Additionally, the spleen showed a notable capacity for granulopoiesis with elevated neutrophils. Moreover, we found elevated IL-6 levels in the skin, blood, and spleen in the model, which was decreased after splenectomy. Treatment with an IL-6 antibody reduced neutrophil formation in both the spleen and skin, which alleviated skin inflammation in psoriatic mice. Additionally, P-STAT3 signaling was decreased following IL-6 antibody treatment. The neutrophil infiltration in spleen and skin was decreased after injection with the inhibitor of P-STAT3, which also alleviated the inflammation of psoriatic model. Thus, IL-6 served as the dominant regulator of spleen granulopoiesis, a process potentially mediated by P-STAT3 signaling.

Conclusions

The spleen plays a crucial role in the immune microenvironment of psoriasis as a major site of granulopoiesis, influencing neutrophil infiltration in the skin of psoriatic mice. Additionally, IL-6 is a key regulator of neutrophil formation in the spleen of psoriatic mice, likely through P-STAT3-dependent mechanisms.

A systematic review of novel Phosphodiesterase-4 inhibitors in the treatment of psoriasis.

Thu, 04 Sep 2025 18:54:24 +0000

Background

Psoriasis is a chronic immune-mediated skin disease that significantly impacts patients' quality of life due to its physical, psychological, and systemic burden. Phosphodiesterase-4 (PDE-4) plays a pivotal role in the inflammatory cascade of the disease through the modulation of intracellular cyclic adenosine monophosphate (cAMP) levels. This systematic review evaluates current evidence on the clinical efficacy and safety of novel PDE-4 inhibitors in the treatment of psoriasis.

Methods

A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science databases through January 18th, 2025, to identify clinical studies evaluating PDE-4 inhibitors in patients with psoriasis. Methodological quality and risk of bias were assessed using the National Institutes of Health (NIH) quality assessment tool and the Murad et al.quality assessment tool.

Results

Out of 1,942 related studies, twelve studies with 642 patients met our inclusion criteria. Among oral PDE-4 inhibitors, oral roflumilast demonstrated consistent improvements in the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI), as well as patient-reported outcomes, in cases with moderate to severe plaque psoriasis. Gastrointestinal symptoms were the most common adverse events. Similarly, orismilast and ME3183 also demonstrated significant PASI reductions and favorable tolerability, while topical agents like crisaborole and PF-07038124 showed a rapid localized response in patients suffering from mild to moderate psoriasis, with minimal adverse effects in sensitive areas, including the face and intertriginous regions.

Conclusion

PDE-4 inhibitors, both oral and topical, demonstrate promising efficacy and acceptable safety profiles in the treatment of psoriasis. To confirm their long-term benefits and improve clinical use, larger-scale studies with longer follow-up and a wider range of patients are required.