Psoriasis (Auckland, N.Z.)最新文献

Background: Psoriasis and substance abuse remains a serious healthcare burden. However, associations between substance abuse and psoriasis have not been elucidated.

Objective: To evaluate the bidirectional associations between substance abuse and psoriasis.

Methods and subjects: Based on the UK Biobank data, we conducted two prospective cohort studies to compare the risk of incident psoriasis in participants with versus without substance abuse (Cohort 1) and the risk of incident substance abuse in participants with versus without psoriasis (Cohort 2). Incident substance abuse (ICD: F10-F19) and psoriasis (ICD: L40) were primarily determined from hospital and primary care data, death registries and self-assessments.

Results: In Cohort 1, 4,097 of 454,245 developed psoriasis during follow-up. Baseline substance abuse was linked to an increased psoriasis risk (hazard ratio [HR]: 2.31, P<0.001), notably in alcohol and tobacco users (HRs: 2.29 and 2.33, P<0.001). Those with high genetic risk and substance abuse had the greatest psoriasis risk (HR: 5.19, P<0.001). In Cohort 2, 25,176 out of 451,547 were diagnosed with substance abuse during follow-up. A notable association between baseline psoriasis and subsequent substance abuse (HR: 1.28, P<0.001) was observed, slightly mediated by depression, anxiety, and sleep quality (1.7% to 3.4%; all P<0.001). Sensitivity analyses showed consistent results.

Conclusion: Our findings identify bidirectional positive associations of substance abuse with psoriasis. This association is especially pronounced in those with both high genetic risk and alcohol or tobacco abuse. It is suggested that clinicians should consider alcohol or tobacco abuse among psoriasis patients to improve their life quality.

Introduction: Psoriasis is a chronic inflammatory disease whose burden peaks in older age groups. Despite the increasing prevalence of elderly patients with moderate-to-severe psoriasis, real-world data on biologics in this population remain limited, particularly for anti-IL-23 agents like guselkumab. This study evaluates the long-term effectiveness and safety of guselkumab in patients aged ≥65 years.

Methods: This retrospective study included 66 patients aged ≥65 years with plaque psoriasis treated with guselkumab 100 mg between June 2019 and June 2024. PASI scores were recorded at baseline and during follow-up visits at weeks 4, 16, 24, 36, 52, 76, and 104. Effectiveness was assessed using PASI75/90/100 and PASI ≤ 2 responses. Multivariable logistic regression with Firth correction identified baseline predictors of PASI90 and PASI100 at weeks 16 and 52. Safety outcomes included treatment-emergent adverse events (TEAEs).

Results: Mean PASI improved from 13.3 at baseline to 1.0 at week 24 and remained stable through week 104. PASI90 and PASI100 were achieved by 83.9% and 71.0% at week 36 and maintained in 69.2% and 61.5% at week 104. Higher baseline PASI independently predicted PASI90 and PASI100 at week 16, while lower eosinophil-to-lymphocyte ratio (ELR) independently predicted PASI100. At week 52, chronic beta-blocker intake and PASI90 at week 16 predicted PASI90 response, while PASI100 was independently associated with low-dose aspirin use and positive family history of psoriasis. TEAEs occurred in 16.7% of patients, with treatment discontinued in 9.1%. Eczematous or urticarial AEs were associated with elevated baseline eosinophils and ELR.

Conclusion: Guselkumab is effective and well tolerated in older adults with psoriasis. Baseline ELR, early PASI response, and chronic use of beta-blockers or aspirin may influence long-term treatment outcomes. While limited by the small sample size (66 patients), our findings represent the longest real-world follow-up to date among older psoriatic patients treated with guselkumab and support its use as a valuable therapeutic option in this population.

Background: Psoriasis is a common chronic inflammatory skin disorder, and the global burden of psoriasis has not been fully disclosed.

Methods: We extracted prevalence, incidence and disability-adjusted life years (DALYs) for psoriasis from 1990 to 2021 in Global Burden of Disease (GBD) and predicted trends in the next 15 years though ARIMA model.

Results: Globally, age-standardized incidence rate (ASIR) of psoriasis increased from 57 cases/100,000 people (95% CI: 55.3~58.8) in 1990 to 62 cases/100,000 people (95% CI: 60.1~63.9) in 2021. Age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life year rate (ASDR) exhibited similar trends of increases. The global ASIR, ASPR, and ASDR for males were significantly higher than females. In 2021, ASIR peaked in the 55-69 ages, while ASPR and ASDR reached peaks between the ages of 65-74. Regionally, ASPR, ASIR, and ASDR in 2021 were highest in high Socio-demographic index (SDI) regions. The highest global regions and countries of ASPR, ASIR and ASDR were Western Europe and Germany, respectively. The East Asia region and Republic of Equatorial Guinea showed most significant growth in these psoriasis indicators since 1990. Furthermore, there was a significant increase in ASIR (8.06%), ASPR (8.14%), and ASDR (13.64%) of global psoriasis over the next 15 years.

Conclusions: Global burden of psoriasis is expected to continuously increase, and strengthening risk-factor management and prioritizing high-risk subgroups (males, elderly, high SDI regions and Western Europe, etc) will be essential for region-specific strategies and future healthcare planning.

Background: Psoriasis is a frequent and complex dermatosis of uncertain origin. A few years ago, a family of gasdermin proteins was implicated in psoriasis pathogenesis. Although the number of therapeutic options for psoriasis is growing, considering the burden of the disease, treatment personalization, and the possibility of side effects or loss of the drug's efficacy, it is important to seek new therapeutic targets.

Objective: The aim of this study was to assess the efficacy of antibodies against gasdermin E (GSDME) in the treatment of psoriatic lesions.

Methods: The study involved 30 male BALB/c mice, 8 weeks old. 5% imiquimod cream was applied topically on the skin to induce psoriatic lesions. The next day after the psoriatic lesions appeared, the antibodies were administered. Mice from the study group received the rabbit polyclonal anti-GSDME antibody intravenously or intraperitoneally. The control group was administered sterile 0.9% saline solution.

Results: The injection of anti-GSDME antibodies to mice with imiquimod-induced psoriasis resulted in the resolution of skin lesions, whereas the injection of saline to the control group did not result in significant changes.

Conclusion: Antibodies targeting GSDME seem to be promising therapeutic agents in psoriasis; however, their utility has to be confirmed in future studies.

Introduction: Psoriasis, characterized by dermatological manifestations, exhibits a systemic impact through its association with serious comorbidities, including inflammatory arthritis, cardiovascular and metabolic diseases, and psychiatric disorders. Current high-cost traditional therapies primarily involve antibodies against psoriasis-associated cytokines. Human antigen R (HuR), an RNA-binding protein that regulates the expression of upstream inflammatory cytokines, is overexpressed in immune disorders. Oligopeptide-based drugs that specifically interact with proteins to block downstream gene expression via structural interactions have garnered significant attention. In this study, we report a peptide-based polymer to target HuR and evaluated their efficacy in treating imiquimod (IMQ)-induced psoriasis-like dermatitis in mice ears.

Methods: Specifically, the HuR-inhibiting peptide (HIP) is PEGlated to obtain methoxypolyethylene glycol-block-poly(γ-benzyl glutamate) (mPEG-b-PBLG) amphiphilic block copolymer. The self-assembly of the mPEG-b-PBLG block copolymer facilitates the formation of polymeric nanoparticles (NPs) in aqueous solutions, resulting in the improvement of the stability and bioactivity of the oligopeptide.

Results: Macroscopic and histological analyses demonstrated that the oligopeptide significantly alleviates the symptoms in psoriasis model mice. Furthermore, the levels of the key cytokine IL-23 and the growth factor VEGF are downregulated. Notably, the HIP effectively targeted the ear skin and did not induce apparent organotoxicity.

Discussion: The promising results demonstrated in this proof-of-concept study provide strong evidence supporting the targeted inhibition of HuR via PEGylated peptide. The observed efficacy in mitigating key inflammatory markers (VEGF and IL-23) highlights the potential of this approach to offer superior specificity and reduced systemic side effects compared to current broad-spectrum immunosuppressants. This HuR-targeting strategy offers a potentially low-cost and effective therapeutic approach for psoriasis patients.

Purpose: Interleukin-17A (IL-17A) drives psoriasis and central nervous system neuroinflammation, but clinical research on whether IL-17A-targeted biotherapy modulates brain activity to improve neuropsychiatric outcomes in psoriasis is lacking. This study aims to investigate brain functional changes, cognitive impairment, and the effects of IL-17A monoclonal antibody therapy in psoriasis vulgaris.

Patients and methods: Regular secukinumab treatment. Meanwhile, 20 healthy controls (HCs) matched in age and gender were enrolled. The patients underwent functional magnetic resonance imaging (fMRI) before treatment and 48 weeks after treatment. The healthy controls also had fMRI scans. It assessed clinical data, cognition/neuropsych status (MoCA, SDS, SAS), disease severity/quality of Life (PASI/DLQI), and brain function via rs-fMRI (ALFF/ReHo).

Results: Compared to healthy controls, the psoriasis vulgaris patients showed increased ALFF in the frontal lobe, as well as increased frontal ReHo. The treatment group showed signal recovery in some brain regions. Patients before treatment had lower MoCA scores vs controls (P < 0.001)) and higher SAS/SDS scores (SAS, P < 0.0001; SDS, P < 0.05). Patients after treatment showed higher MoCA scores vs before treated (P < 0.05), similar to controls, with lower SAS scores (P < 0.0001) and reduced PASI/DLQI (P < 0.0001).

Conclusion: Psoriasis is associated with brain dysfunction and neuropsychiatric symptoms. IL-17A antibody therapy improves skin symptoms, restores brain function, and alleviates neuropsychiatric issues vs untreated patients, supporting multidimensional treatment.

Background: Psoriasis (PsO) is a prevalent chronic disease affecting millions, with biologic therapies like secukinumab showing efficacy. With the extensive and prolonged use of secukinumab, identifying strategies for successful dose tapering has emerged as a recent challenge.

Objective: This retrospective study aims to identify predictors of successful secukinumab dose tapering in patients with moderate-to-severe plaque psoriasis.

Methods: This retrospective study included patients who received secukinumab 300 mg weekly for 5 weeks, then every 4 weeks, achieving and maintaining Psoriasis Area and Severity Index (PASI) 90 for ≥6 months. Statistical analyses included the Mann-Whitney U-test, Friedman M test, and logistic regression (P<0.05).

Results: Among the 75 secukinumab-treated patients, 40 (53.33%) successfully tapered their dosage. BMI, dose tapering timing, and pre-tapering treatment duration were significant predictors of tapering success. Seasonal effects were observed, with autumn and winter attempts having an increased risk of failure. PASI 75 and PASI 90 rates dropped from week 6 to 12, with no serious adverse events.

Conclusion: Lower BMI, dose tapering initiation in spring and summer, and rapid PASI 90 achievements are associated with successful secukinumab dose tapering. These findings suggest that, under appropriate clinical conditions, dose tapering may be a feasible strategy to maintain disease control while potentially reducing treatment-related costs and minimizing the risk of adverse effects.

Background: 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.

Background: To identify new targets for protein-based treatments in psoriasis and evaluate the possible negative impacts of these druggable proteins.

Methods: We carried out an extensive analysis of the entire set of proteins in the blood (proteome-wide) to determine if there are causal links between certain blood proteins and the likelihood of developing psoriasis. The proteins were selected from the UK Biobank Pharma Proteomics Project (UKBPPP) database, which includes genetic data for 2,940 different blood proteins. We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome-wide association study (GWAS) of psoriasis.

Results: Our research discovered a strong genetic link between plasma APOF, ATP6V1G2, IFNLR1, CRELD1, PRSS8, and TNF proteins and a higher chance of having psoriasis. These proteins share genetic variations associated with psoriasis (PPH3+PPH4>0.8). The ROC curves derived from these protein quantity trait loci (pQTLs) demonstrate that they can distinguish between individuals with psoriasis and those without. The druggable gene analysis showed that simvastatin is related to TNF based on the Drug SIGnatures DataBase webtool.

Conclusion: Our study has explored the causal relationships between six blood proteins and psoriasis, offering a detailed insight into potential therapeutic targets. Among them, simvastatin might have an effect on psoriasis via TNF.

Introduction: Psoriasis is a chronic autoimmune skin disorder with a complex genetic basis. However, the codon usage patterns and nucleotide features of psoriasis-related genes remain unexplored, despite their potential to influence gene expression and disease progression.

Methods: We analyzed 79 psoriasis-associated genes to investigate codon usage bias (CUB) and nucleotide composition. Metrics included GC content, effective number of codons (ENC), and relative synonymous codon usage (RSCU). Evolutionary influences were assessed using correspondence analysis, parity rule 2 (PR2) plots, and neutrality plots.

Results: Functional enrichment analysis identified pathway involvement. Comparative genomic analysis evaluated differences in coding sequence and UTR lengths and GC content relative to the genome-wide background. Psoriasis-related genes showed high GC content (mean = 53.3 ± 9.3%) with a strong preference for GC-ending codons, especially at the third codon position (GC3 = 60.6 ± 16.1%). RSCU analysis revealed frequent use of GCC (alanine), CTG (leucine), and GTG (valine). While the mean ENC (46.2 ± 9.9) suggested moderate codon bias, several genes displayed strong bias (ENC < 30). Selection pressure accounted for 71% of codon usage variation, with mutation pressure contributing 29%. Functional enrichment showed significant involvement in IL-17 (FDR = 3.4×10^-3), JAK-STAT (FDR = 3.4×10^-3), and TNF (FDR = 8.0×10^-³) signaling pathways. These genes also tended to have shorter coding sequences and 5'UTRs and higher GC content compared to genome-wide averages.

Conclusion: In conclusion, this study reveals that psoriasis-related genes are under strong selective pressure, enriched in key inflammatory pathways, and exhibit codon and nucleotide features that may optimize expression in inflamed tissues. These insights have translational relevance for designing codon-optimized mRNAs, gene therapies, and diagnostic tools tailored to autoimmune diseases like psoriasis.