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Neue Studien
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BE SURE (NCT03412747), BE VIVID (NCT03370133), BE RADIANT (NCT03536884), BE READY (NCT03410992), BE BRIGHT (NCT03598790).Weiterlesen
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Psoriasis is a chronic inflammatory autoimmune disease that affects physical and mental health. Mental stress has been shown to exacerbate human psoriasis by unknown mechanism.Methods
Peripheral blood mononuclear cells (PBMCs) were collected from patients with psoriasis and mental stress-treated psoriatic mice. The expression levels of TLR9/MyD88/NF-κB pathway-related molecules were analyzed by qRT-PCR and western blotting. Histological examination of skin lesions was examined using hematoxylin-eosin staining. The ratios of Treg/CD4+T cells and Th17/Treg cells were determined by flow cytometry. The associations among mental stress, the TLR9/MyD88/NF-κB pathway, and psoriasis were explored using pharmacological inhibitors and lentiviral transfection.Results
Our findings demonstrated a significant upregulation of TLR9/MyD88/NF-κB pathway-associated molecules in the PBMCs of psoriasis patients, accompanied by elevated expression of inflammatory factors. These observations were validated using a mouse model of psoriasis. Notably, mental stress was shown to activate the TLR9/MyD88/NF-κB pathway and enhance inflammatory factor production, while simultaneously increasing the Th17/Treg ratio and decreasing the Treg/CD4+T ratio. Therapeutic interventions including antipsychotic sertraline, pathway-specific inhibitors, and lentiviral transfection significantly ameliorated inflammatory markers and improved psoriasis severity grading.Conclusion
The results of this study demonstrates that mental stress induces inflammation and immune dysregulation, exacerbating psoriasis progression. These findings provide valuable insights into the pathophysiological mechanisms underlying psoriasis progression, particularly the mental stress-mediated immunoregulatory axis.Weiterlesen
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Generalized pustular psoriasis (GPP) is rare, chronic, and associated with life-threatening complications. We investigated the burden of GPP in France.Methods
Using data from 2010 to 2021 in the Système National des Données de Santé database, healthcare resource utilization (HCRU), costs, comorbidities, mortality, and treatments were compared among GPP (N = 4351), plaque psoriasis (N = 12,945), and general population (N = 12,981) cohorts, matched for sex, age, Charlson Comorbidity Index (CCI) score, and region. GPP prevalence and incidence were also investigated.Results
Annually, there were 0.5-0.8 new GPP cases per 100,000 people. Across the cohorts, 54.5-54.7% of people were male, with mean age 58.7-59.5 years and mean CCI score 1.98-2.06. The GPP cohort incurred significantly greater HCRU and costs versus the plaque psoriasis and general population cohorts, including greater proportions of patients receiving emergency care (78% vs 63% and 55%) and intensive care (28% vs 17% and 14%), longer hospitalizations (mean 38.5 vs 26.2 and 22.4 days per patient), and higher medication costs (€4360 vs €1991 and €1543 per patient-year), respectively. Despite similar CCI scores, GPP was associated with more cardiometabolic and psychological comorbidities versus the plaque psoriasis and general population cohorts, e.g., hypertension (37% vs 21% and 20%), obesity (21% vs 9% and 6%), depression (13% vs 4% and 4%), alcohol abuse (16% vs 3% and 3%), and sleep disorders (8% vs 4% and 3%), respectively. Treatments in the GPP cohort were those used for plaque psoriasis, including topical steroids (77%), systemic steroids (50%), and biologics (23%). Twelve-month survival was 86.9% (GPP), 97.5% (plaque psoriasis), and 90.0% (the general population).Conclusion
HCRU, costs, and comorbidities with GPP were often double those for comparator cohorts, and mortality was higher. These findings highlight the need to use GPP-targeted treatments that improve patient outcomes and may reduce the burden on healthcare systems.Weiterlesen
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Systemic inflammation indices derived from complete blood counts (CBC) are accessible markers of inflammatory burden, but their relationship with circulating cytokines in psoriasis remains unclear. We investigated associations between CBC-derived indices and serum cytokines in psoriasis.Materials and methods
In this cross-sectional study, we included 28 patients with psoriasis and 23 healthy controls. Serum IL-17, IL-22, IL-23, IL-31, IL-33, IL-36, TNF-α, TGF-β, and IFNγ were quantified by ELISA. CBC-derived indices were computed (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). Case-control comparisons used the full sample. Cytokine-index associations were evaluated in psoriasis patients using bivariate correlations and multivariate GLM adjusted for age, smoking, and NAFLD. Multiplicity was controlled using Benjamini-Hochberg false discovery rate (BH-FDR); prespecified sensitivity analyses used log-transformed cytokines and Spearman correlations.Results
Psoriasis patients had higher levels of all cytokines (all p < 0.001) and higher SIRI versus controls (p < 0.001; q = 0.005). PIV showed a nominal case-control difference (p = 0.022) that did not remain significant after BH-FDR (q = 0.055), while NLR, PLR, and SII did not differ. In adjusted multivariate GLM, TGF-β showed a global association with the joint set of indices (Pillai's trace = 0.295; p = 0.039) that did not survive BH-FDR (q = 0.507) and was attenuated with log-transformation. Nominal univariate effects for TNF-α on SIRI (F = 4.600; p = 0.039) and PIV (F = 5.660; p = 0.023) did not remain significant after BH-FDR.Conclusions
SIRI was consistently elevated in psoriasis, whereas PIV showed a nominal difference versus controls. Across exploratory analyses, SIRI and PIV showed the most consistent directional co-variation with cytokines, but associations were modest. These findings are hypothesis-generating and support further validation in larger cohorts to determine whether CBC-derived indices can serve as scalable adjunct markers of inflammatory activity in psoriasis.Weiterlesen
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Given the proinflammatory cascade elicited by tumor necrosis factor-α (TNF-α) in psoriasis, multiple TNF-α-targeted biologics have been developed for psoriasis treatment. Although systemic macromolecular biologics are widely used, a crucial therapeutic gap remains for mild-to-moderate psoriasis, underscoring an unmet need for more effective topical drugs suppressing TNF-induced inflammatory signaling.Objective
To identify a novel potent natural small-molecule drug suppressing TNF-induced inflammatory signaling and elucidate its therapeutic mechanism in psoriasis.Methods
First, candidate small-molecule drugs were screened out through a high-throughput screening platform. Next, the therapeutic effect of Isolinderalactone was evaluated through topical application in the imiquimod (IMQ)-induced psoriasis-like mouse model. Subsequently, RNA sequencing (RNA-seq) analysis of TNF-α-stimulated HaCaT cells and epidermis of IMQ-treated mice identified key transcriptomic alterations induced by Isolinderalactone treatment. Finally, anti-psoriasis effects and underlying mechanisms of Isolinderalactone were verified in both in vivo and in vitro experiments.Results
Isolinderalactone was identified as a potent drug suppressing TNF-related signaling with low cytotoxicity. Topical application of Isolinderalactone significantly alleviated IMQ-induced psoriasis-like dermatitis. Conjoint analysis of RNA-seq for TNF-α-stimulated HaCaT cells and epidermis from lesions of IMQ-treated mice revealed Isolinderalactone downregulated the expression of TNF-α, interleukin-17 (IL-17) and S100-related inflammatory factors in epidermal keratinocytes. Mechanistically, Isolinderalactone significantly inhibited the TNF-α/STAT3 inflammatory pathways in epidermal keratinocytes and exerted an anti-inflammatory effect.Conclusion
Isolinderalactone exhibits anti-inflammatory activity through multiple mechanisms, highlighting the potential of topical Isolinderalactone therapy for mild-to-moderate psoriasis.Weiterlesen
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Psoriatic arthritis (PsA) is an inflammatory, chronic and progressive musculoskeletal disease associated with psoriasis. The validation of the Spanish version of the Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) questionnaire has been published previously. The present analysis studied the performance of the PURE-4 questionnaire for the early detection of PsA one year before its diagnosis.Materials and methods
This was an observational multicenter study, including two cross-sectional assessments, with primary data collection in routine clinical practice in Spain. Adult patients with psoriasis and confirmed not having PsA diagnosis during Assessment I completed Assessment II by the rheumatologist one year (±2 months) after answering the PURE-4 questionnaire. This work presents the results of Assessment II, to confirm/rule out the presence of PsA in patients with psoriasis one year after PURE-4 answering. The analysis, involving the results from Assessment II, will evaluate the performance of the PURE-4 questionnaire for the early detection of potential PsA in terms of sensitivity and specificity.Results
There were 219 evaluable patients, 56.2% male, and the mean (standard deviation [SD]) age was 46.8 (12.5) years. At one year, the PsA diagnosis was confirmed in 12 (5.5%) patients, representing 26.1% of the total number of patients with PsA diagnosed since the beginning of the study. The mean (SD) PURE-4 score was 2.4 (1.1) for patients with PsA and 1.2 (1.2) for patients without a diagnosis of PsA (p = 0.0016). The area under the receiver-operating characteristic (ROC) curve confirmed the good quality of the questionnaire (0.7618; 95% CI: 0.6530-0.8706; n = 217). PURE-4 showed a sensitivity of 75.0% and a specificity of 62.9%.Conclusions
The PURE-4 questionnaire offers good clinimetric capabilities for the early detection of PsA with a score ≥2. Of the total number of patients with PsA, one in four were detected one year after answering positively to the questionnaire, which would help to predict which patients are at high risk of developing PsA. The authors reinforce the recommendation to closely follow up with these patients.Weiterlesen
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Psoriatic disease has a complex effect on bone metabolism, resulting in both pathological bone formation and bone resorption. However, microstructural changes in cortical and trabecular compartments remain poorly understood. The aim of this study was to investigate the prevalence and determinants of bone microarchitectural damage in patients with psoriatic disease.Methods
We performed a cross-sectional study in patients with psoriasis (PsO), psoriatic arthritis (PsA) and age-matched healthy controls (HCs) recruited into the Department of Dermatology and Rheumatology of Verona centre. We conducted high-resolution peripheral quantitative CT of the radius and finger joints of the non-dominant hand. Bone microstructure parameters and finite element analysis (uFEA) were calculated.Results
51 patients with PsO and 39 patients with PsA were consecutively enrolled in the study. 24 age-matched HCs were enrolled. Distal radius total and cortical volumetric bone mineral density (Ct.BMD) levels were lower in patients with PsA and PsO compared with HC. On distal radius uFEA analysis, we found a significant reduction of stiffness in PsA compared with both HC and PsO. At the distal interphalangeal (DIP) joints, Ct.BMD and trabecular volumetric bone mineral density were lower in PsA and PsO compared with HC. Nail involvement in psoriatic disease was negatively associated with bone stiffness at the proximal and distal region of the DIPs.Conclusion
Psoriatic disease negatively impacted bone integrity. Patients with psoriatic disease seemed to have lower bone density and more microarchitectural alteration that impacted on biomechanics properties. Nail involvement was associated with decreased bone stiffness in psoriatic disease.Weiterlesen
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From skin clearance to psychological wellbeing: real-world outcomes of biologic therapy in psoriasis
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Skin is the largest organ of the human body. It continuously encounters environmental toxicants, including airborne pollutants, which may induce many skin disorders, such as psoriasis. However, evidence on the association between airborne pollutants and psoriasis prevalence in China remains limited.Methods
We used nationwide inpatient diagnostic data on psoriasis from 2021 to 2023, encompassing 149 744 cases across 31 provinces, municipalities, and autonomous regions in China, along with corresponding air pollution data. We analysed the spatial distribution and clustering patterns of psoriasis using the spatial autocorrelation analysis. We employed Pearson correlation analysis and Geodetector to explore the spatial heterogeneity of psoriasis and its association with airborne pollutants at the provincial level. We assessed the explanatory power of individual airborne pollutants and their combined effects on psoriasis prevalence.Results
Pearson correlation analysis revealed that PM10 (r = 0.604), PM2.5 (r = 0.429), air quality index (AQI) (r = 0.542), and NO2 (r = 0.476) have significant positive correlations with psoriasis prevalence. Psoriasis and its subtypes exhibited significant spatial heterogeneity and diverse clustering patterns across regions. Geodetector identified PM10 (q = 0.357; P = 0.000), AQI (q = 0.315; P = 0.000), and O3 (q = 0.264; P = 0.000) as key contributors to this spatial heterogeneity. Interactive detection analysis further revealed that the combined effects of specific pollutant pairs, including PM2.5 and SO2 (q = 0.790), PM10 and SO2 (q = 0.727), as well as O3 and SO2 (q = 0.704), played a pivotal role in explaining the prevalence of psoriasis. The other combinations also showed an important impact on psoriasis subtypes, including psoriasis vulgaris (PM2.5 and SO2) (q = 0.792), psoriasis erythematous (PM2.5 and SO2) (q = 0.852), psoriatic arthritis (PM10 and O3) (q = 0.840), and nail psoriasis (PM10 and O3) (q = 0.789).Conclusions
The airborne pollutants influence psoriasis prevalence and its subtypes. With the largest global study of the Asian population, we provide novel insights into the impact of air pollution on psoriasis, guiding future public health policies and clinical interventions.Weiterlesen
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Biologic therapies have transformed the management of moderate-to-severe psoriasis but are associated with long-term treatment burden and substantial healthcare costs. Dose spacing, defined as extending dosing intervals in patients with controlled disease, has emerged as a potential optimization strategy. However, data on real-world implementation and clinician perspectives remain limited.Methods
We conducted a national, cross-sectional survey among Portuguese dermatologists experienced in prescribing biologic therapies for psoriasis. An anonymous, web-based questionnaire assessed clinicians' perspectives and real-world practices regarding biologic dose spacing, including eligibility criteria, preferred biologic classes, implementation strategies, outcomes after loss of disease control, and limiting clinical factors.Results
Seventy-five dermatologists completed the survey (response rate 48.4%). All respondents considered dose spacing feasible. The most frequently cited eligibility criteria were absolute Psoriasis Area and Severity Index (PASI) ≤ 1, body surface area (BSA) ≤ 1%, and a 90% improvement in PASI (PASI 90). Interleukin-23 (IL-23) inhibitors were perceived as the most suitable class for dose spacing (93.3%). In routine practice, dose spacing was applied frequently by 30.7% of respondents and occasionally by 48.0%. Most clinicians (69.3%) required more than 12 months of sustained disease control before initiating dose spacing, predominantly using progressive extension of dosing intervals (96.0%). IL-23 inhibitors were the biologics most frequently dose-spaced in current practice. Following loss of disease control, 86.7% reported successful recapture of response after reintroduction of standard dosing. The main factors limiting dose spacing were a history of difficult-to-control psoriasis (77.3%) and concomitant psoriatic arthritis (72.0%).Conclusion
Biologic dose spacing is already integrated into clinical practice in Portugal. Further prospective studies are needed to establish standardized criteria and guide safe implementation.Weiterlesen
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To evaluate the long-term efficacy of interleukin (IL)-17A inhibition with secukinumab on structural bone changes and clinical outcomes in psoriatic arthritis (PsA).Methods
We conducted a phase-IV non-interventional study on adult patients with active PsA using high-resolution peripheral quantitative CT (HR-pQCT) and MRI of the hand over 48 months. All participants received secukinumab treatment and were followed up according to clinical practice, with repeated HR-pQCT and MRI. Number and volume of erosions, bone density, cortical and trabecular microarchitecture and bone biomechanical properties were assessed based on HR-pQCT scans. MRI synovitis, tenosynovitis, osteitis, periarticular inflammation, erosions and osteoproliferation were quantified by Psoriatic Arthritis MRI Score (PsAMRIS)-Outcome Measures in Rheumatology (OMERACT) score. Study outcomes included drug survival and changes from baseline in disease activity, functional status and imaging-detected inflammation and damage.Results
32 patients with PsA (40.6% female, mean age 56±7.5 years) were enrolled. Drug survival rate was 68.8% at 48 months. Secukinumab was highly effective in all PsA disease domains, with significant improvements in Disease Activity Score 28 (p<0.001), Leeds Enthesitis Index (p=0.027), Psoriasis Area and Severity Index (p=0.001), C reactive protein (p=0.09), Psoriatic Arthritis Impact of Disease (p<0.001) and pain (p<0.001). Functional status measured by the Health Assessment Questionnaire remained stable. On HR-pQCT, bone density, microarchitecture and biomechanics were preserved. There was no progression of bone erosions (all changes were not significant). On MRI, PsAMRIS erosion and osteoproliferation subitems increased marginally (+1.4 and +0.8, respectively), while inflammatory changes remained stably low. No major safety signals emerged.Conclusion
Multimodal imaging with HR-pQCT and MRI showed no relevant progression of structural bone damage over 48 months in patients with PsA treated with secukinumab, suggesting that anti-IL-17A therapy induces sustained osteoprotective effects in PsA.Weiterlesen
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Psoriasis is a persistent, chronic autoimmune skin disease that affects around 2% of the global population. Conventional therapies often exhibit limited efficacy, systemic side effects, and poor patient compliance due to long-term treatment needs.Materials & methods
This study focused to develop and optimize a sulfasalazine-loaded microemulsion (SSZ-ME) for topical delivery to enhance skin penetration and therapeutic efficacy in psoriasis. Pseudo-ternary phase diagrams were prepared to identify the optimal surfactant mixture, with Tween 80 and Polyethylene Glycol 400 selected in a 2:1 ratio. A 23 factorial design was used to optimize formulation parameters, focusing on oil and surfactant mixture effects on globule size and viscosity.Results and conclusions
The resulting microemulsions showed globule sizes between 60 ± 0.42 to 349 ± 0.13 nm, with optimal viscosity. In vitro release studies confirmed sustained drug release over 24 hours, following first-order kinetics. Skin permeation studies demonstrated enhanced drug penetration with SSZ-ME, while histopathological analysis revealed significant improvements in psoriatic symptoms in mice treated with 4% SSZ-ME compared to 2% SSZ-ME and marketed formulation. Blood analysis confirmed minimal systemic absorption and localized action. These results suggest that SSZ-ME offers a promising, patient-compliant, and effective topical therapy for psoriasis with improved therapeutic outcomes and minimal systemic exposure.Weiterlesen
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