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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
- 236 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
- 225 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
- 242 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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Although IL-17 inhibitors like Secukinumab and Ixekizumab have shown significant efficacy in psoriasis, the impact of early intervention with biologics to modify the disease course and achieve long-term remission remains unclear.Objectives
To examine the potential of early intervention with IL-17 inhibitors for disease modification in psoriasis.Methods
We conducted a multicenter retrospective cohort study on moderate-to-severe plaque psoriasis patients who received at least 4 weeks of treatment with Secukinumab or Ixekizumab between April 2019 and April 2023, taking the relapse rate one year after cessation of treatment as the primary endpoint.Results
Among 400 patients who discontinued treatment after achieving PASI90, the median relapse time was 3.29 months(approximately 14 weeks). Of 141 patients who discontinued treatment after achieving PASI90 for over a year, 24 (88.89%) in the ultra-short disease duration(USDD, psoriasis duration ≤ 1 year) group and 33 (82.5%) in the short disease duration(SDD, psoriasis duration ≤ 2 year) group achieved one year of drug-free remission.Limitations
The potential impact of early intervention on comorbidity development was not addressed in this study.Conclusion
Early intervention with IL-17 inhibitors leads to faster responses and may promote disease modification in psoriasis.Weiterlesen
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Residual confounding effects and disease severity are attributed to controversial results in studies of psoriatic disease (PsD) and mortality. We aimed to evaluate the risk of mortality in patients with incident PsD, compared to matched controls from the population.Methods
We used the nationwide, population-based insurance claim datasets in Taiwan from 2010 to 2018. Incident cases of PsD were identified by International Classification of Diseases (ICD) codes. A nonexposed cohort was established through propensity score matching (PSM). Deaths were identified via the National Mortality Database. We evaluated the risk of all-cause mortality in PsD compared to the PSM nonexposed individuals using Cox regression. The mortality risk was evaluated in patients with more severe disease stratified by systemic therapy use and having psoriatic arthritis (PsA).Results
There were 108,642 patients with incident PsD (40.2% women) and an equal number of PSM non-PsD individuals. Compared to the age- and sex-matched controls, there was a higher risk of mortality among patients with PsD (adjusted hazard ratio [aHR] 1.73, 95% CI 1.68-1.77, P < 0.001). After PSM, we found an attenuated but persistent higher risk of mortality in PsD compared to controls (aHR 1.20, 95% CI 1.16-1.24). There was a trend of higher mortality in patients exposed to biologic therapies, but not for PsA.Conclusion
There was an increased risk of all-cause mortality in individuals with PsD compared to individuals without PsD before and after both PSM and adjustment for comorbidities. The risk of mortality was higher in patients with psoriasis but not in patients with PsA as compared to controls.Weiterlesen
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To describe the psoriatic phenotype associated with psoriatic arthritis (PsA) METHODS: Based on the previously published PURE 4 validation study, this work aims to describe the sociodemographic and clinical characteristics, as well as the PURE-4 questionnaire outcomes, of psoriasis patients who completed the study. It compares those diagnosed with PsA during the study to those with only psoriasis . The variables compared were age, gender, time since diagnosis of psoriasis, psoriasis location, psoriasis treatment, Psoriasis Area and Severity Index (PASI), and Dermatology Life Quality Index (DLQI).Results
The study included 253 psoriasis patients, from whom 46 developed PsA (28 [60.9%] male; mean age 48.9 [11.1]) during the study. At baseline, patients who developed PsA had more involvement of psoriasis in the neck (13.0% vs. 3.4%, p<0.01), knees (71.4% vs. 50.0%, p=0.02), hands (40.0% 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 [5.6] vs. 6.8 [5.0], p=0.03) and DLQI (9.9 [6.9] vs. 7.6 [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% in Assessment I to 91.7% in Assessment II (91.7% vs. 45.4%, p<0.01).Conclusion
Greater psoriasis involvement in neck, knees, hands, and feet as well as high impact areas of patients who developed PsA suggests additional information on arthritogenic phenotype of psoriasis in our study population compared to locations generally linked to arthritis risk (nail or scalp).Weiterlesen
- 205 Aufrufe
Only limited data is available on the benefit of brodalumab 210 mg, an IL-17 receptor A antagonist, on patient-reported outcomes (PROs) in different psoriasis severity groups under real-world-evidence (RWE) conditions.Methods
LIBERO, a prospective, multicenter, 12- and 52-weeks (W) non-interventional study on brodalumab in adult patients with plaque-type psoriasis assessed its short- and long-term impact on PROs in mild, moderate and severe psoriasis defined by Psoriasis Area Severity Index (PASI).Results
200 (31.3%) patients with severe (PASI ≥ 20), 263 (41.2%) with moderate (PASI = 10-19) and 168 (26.3%) with mild (PASI < 10) psoriasis were analyzed. In all severity groups a rapid and sustained reduction of mean(m) PASI was observed as of W2. 76.7, 84.9 and 82.0% of patients assessed their psoriasis as being clear/almost clear in mild, moderate and severe subgroups and mean Dermatological Life Quality Index improved from 11.2, 14.3 and 17.1 to 3.2, 2.9 and 3.8. 73.7% of patients rated brodalumab as being quite/very beneficial (Patient Benefit Index, PBI) and were quite/very satisfied with the treatment (TSQM-9). Regaining disease control and reducing physical impairment achieved highest PBI-scores.Conclusion
LIBERO confirms the benefit of brodalumab on PROs including rapid and complete clearance of skin lesions, quality of life and individual patient benefits - irrespective of their disease severity.Weiterlesen
- 219 Aufrufe
Psoriasis is a chronic inflammatory disease associated with abnormalities in the immune system. Microsomal prostaglandin E synthase-1 (mPGES-1), a terminal enzyme for prostaglandin (PG) E2 biosynthesis, is highly expressed in the skin of psoriasis patients. However, the detailed role of mPGES-1 in psoriasis remains unclear. In the present study, we aimed to investigate the role of mPGES-1 in psoriasis-like skin inflammation induced by imiquimod (IMQ), a well-established model of psoriasis.Methods
Psoriasis was induced in mPGES-1-deficient (mPGES-1-/-) and wild-type (WT) mice by administering IMQ for 6 days. Psoriasis was evaluated based on the scores of the macroscopic symptoms, including skin scaling, thickness, and redness, and on the histological features. The skin expression of mPGES-1 was determined by real-time polymerase chain reaction and Western blotting. The impact of mPGES-1 deficiency on T-cell immunity was determined by flow cytometry and γδ T-cell depletion in vivo with anti-T-cell receptor (TCR) γδ antibody.Results
The inflamed skin of mPGES-1-/- mice showed severe symptoms after the administration of IMQ. Histological analysis further showed significant exacerbation of psoriasis in mPGES-1-/- mice. In WT mice, the mPGES-1 expression was highly induced at both mRNA and protein levels in the skin, and PGE2 increased significantly after IMQ administration, while the PGE2 production was largely abolished in mPGES-1-/- mice. These data indicate that mPGES-1 is the main enzyme responsible for PGE2 production in the skin. Furthermore, the lack of mPGES-1 increased the numbers of IL-17A-producing γδ T cells in the skin with IMQ-induced psoriasis, and γδ T-cell depletion resulted in a reduction of the facilitated psoriasis symptoms under the condition of mPGES-1 deficiency.Conclusions
Our study results demonstrate that mPGES-1 is the main enzyme responsible for skin PGE2 production, and that mPGES-1 deficiency facilitates the development of psoriasis by affecting the development of T-cell-mediated immunity. Therefore, mPGES-1 might impact both skin inflammation and T-cell-mediated immunity associated with psoriasis.Weiterlesen
- 216 Aufrufe