Onset Of Psoriasis Research Articles

The Role of Vitamin D3 Deficiency and Colonization of the Oral Mucosa by Candida Yeast-like Fungi in the Pathomechanism of Psoriasis

Psoriasis is a chronic inflammatory skin disease with complex pathogenesis and variable severity. Performed studies have indicated the impact of vitamin D3 deficiency on the pathogenesis of psoriasis and its severity. However, there is no clear evidence of the influence of the mucosal microbiome on the onset and progression of psoriasis. This review aims to present the current evidence on the role of vitamin D3 and colonization of the oral mucosa by Candida yeast-like fungi in the pathogenesis of psoriasis. Candida albicans is a common yeast that can colonize the skin and mucosal surfaces, particularly in individuals with weakened immune systems or compromised skin barriers. In psoriasis, the skin’s barrier function is disrupted, potentially making patients more susceptible to fungal infections such as Candida. Since patients with psoriasis are at increased risk of metabolic syndrome, they may experience the vicious circle effect in which chronic inflammation leads to obesity. Vitamin D3 deficiency is also associated with microbiological imbalance, which may promote excessive growth of Candida fungi. Under normal conditions, the intestinal and oral microflora support the immune system. Vitamin D3 deficiency, however, leads to disruption of this balance, which allows Candida to overgrow and develop infections.

Cell damage shifts the microRNA content of small extracellular vesicles into a Toll-like receptor 7-activating cargo capable to propagate inflammation and immunity

BackgroundThe physiological relevance of cell-to-cell communication mediated by small extracellular vesicle-encapsulated microRNAs (sEV-miRNAs) remains debated because of the limiting representativity of specific miRNAs within the extracellular pool. We hypothesize that sEV-miRNA non-canonical function consisting of the stimulation of Toll-like receptor 7 (TLR7) may rely on a global shift of the sEV cargo rather than on the induction of one or few specific miRNAs. Psoriasis represents an ideal model to test such hypothesis as it is driven by overt activation of TLR7-expressing plasmacytoid dendritic cells (pDCs) following keratinocyte damage.MethodsTo mimic the onset of psoriasis, keratinocytes were treated with a cocktail of psoriatic cytokines or UV-irradiated. SmallRNA sequencing was performed on sEVs released by healthy and UV-treated keratinocytes. sEV-miRNAs were analyzed for nucleotide composition as well as for the presence of putative TLR7-binding triplets. Primary human pDCs where stimulated with sEVs +/- inhibitors of TLR7 (Enpatoran), of sEV release (GW4869 + manumycin) and of TLR7-mediated pDC activation (anti-BDCA-2 antibody). Secretion of type I IFNs and activation of CD8+T cells were used as readouts. qPCR on psoriatic and healthy skin biopsies was conducted to identify induced miRNAs.ResultssEV-miRNAs released by damaged keratinocytes revealed a significantly higher content of TLR7-activating sequences than healthy cells. As expected, differential expression analysis confirmed the presence of miRNAs upregulated in psoriatic skin, including miR203a. More importantly, 76.5% of induced miRNAs possessed TLR7-binding features and among these we could detect several previously demonstrated TLR7 ligands. In accordance with this in silico analysis, sEVs from damaged keratinocytes recapitulated key events of psoriatic pathogenesis by triggering pDCs to release type I interferon and activate cytotoxic CD8+T cells in a TLR7- and sEV-dependent manner.DiscussionOur results demonstrate that miR203a is just one paradigmatic TLR7-activating miRNA among the hundreds released by UV-irradiated keratinocytes, which altogether trigger pDC activation in psoriatic conditions. This represents the first evidence that cell damage shifts the miRNA content of sEVs towards a TLR7-activating cargo capable to propagate inflammation and immunity, offering strong support to the physiological role of systemic miRNA-based cell-to-cell communication.

Association Between Non-HDL to HDL Cholesterol Ratio (NHHR) and Psoriasis in Adults: A Cross-Sectional Study Using 2009-2014 Data.

Because of its possible significance in metabolic diseases, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered attention as a novel and trustworthy lipid biomarker. Psoriasis may be linked to metabolic problems and obesity, according earlier research. Uncertainty surrounds the relationship between NHHR and the onset of psoriasis, though. The primary aim of this investigation was to examine the relationship between NHHR and psoriasis. This cross-sectional analysis used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2014. The association between psoriasis and NHHR was examined using multivariate logistic regression, and smoothed curve fitting was done to explore the non-linear relationship. Furthermore, Subgroup and sensitivity studies were performed in order to confirm the robustness of the findings. Psoriasis and NHHR were shown to be positively correlated in 15,951 adult individuals who were at least 20 years old. Psoriasis risk rose by 7% for each unit increase in NHHR [1.07 (1.01, 1.14)]. Individuals in the highest NHHR tertile were 39% more likely compared to those in the bottom tertile to have psoriasis [1.39 (1.09, 1.78)]. Across subgroups, this favorable connection remained consistent. Elevated NHHR levels are positively correlated with an upsurge chance of psoriasis in the adult population in the United States. The significance of NHHR as an indication for early psoriasis risk assessment is shown by this study.

MiR‑155 promotes an inflammatory response in HaCaT cells via the IRF2BP2/KLF2/NF‑κB pathway in psoriasis.

Psoriasis is a chronic inflammatory skin condition with numerous causes, including genetic, immunological and infectious factors. The course of psoriasis is long and recurrence is common; pathogenesis is not completely understood. However, there is an association between advancement of psoriasis and aberrant microRNA (miR or miRNA)‑155 expression. Through bioinformatics, the present study aimed to analyze the differentially expressed genes and miRNAs in psoriasis and its biological mechanism and function psoriatic inflammation. First of all, differentially expressed genes (DEGs) and miRNAs (DEMs) in patients with psoriasis were identified using GEO2R interactive web application. A psoriasis inflammatory model was established using lipopolysaccharide (LPS)‑treated HaCaT keratinocytes, which were transfected with miR‑155 mimic or inhibitor. Cell Counting Kit‑8 was used for the assessment of cell viability and proliferation, and changes in the cell cycle were examined using flow cytometry. ELISA and reverse transcription‑quantitative PCR (RT‑qPCR) were used to detect the expression levels of the inflammatory factors IL‑1β and IL‑6. The dual‑luciferase reporter assay was used to verify the targeting association between miR‑155‑5p and IFN regulatory factor 2 binding protein 2 (IRF2BP2). To verify the targeting association of miR‑155 and the IRF2BP2/kruppel‑like factor 2 (KLF2)/NF‑κB signaling pathway, expression levels of IRF2BP2, KLF2 and p65 were identified by RT‑qPCR and western blotting. IRF2BP2 levels were also confirmed by immunofluorescence, in conjunction with bioinformatics database analysis. Overexpression of miR‑155 inhibited proliferation of HaCaT cells and increased the number of cells in S phase and decreasing number of cells in G1 and G2 phase. In the LPS‑induced inflammatory state, miR‑155 overexpression heightened the inflammatory response of HaCaT cells while inhibition of miR‑155 lessened it. Suppression of inflammatory cytokine expression by miR‑155‑5p inhibitor was reversed by knockdown of IRF2BP2. miR‑155 was shown to interact with IRF2BP2 to negatively regulate its expression, leading to decreased KLF2 expression and increased p65 expression and secretion of inflammatory factors, intensifying the inflammatory response of HaCaT cells. Therefore, miR‑155 may contribute to development of psoriasis by inducing tissue and cell damage by increasing the inflammatory response of HaCaT cells via the IRF2BP2/KLF2/NF‑κB pathway. In conclusion, the results of the present study offer novel perspectives on the role of miR‑155 in the onset and progression of psoriasis.

Joint exposure to multiple air pollutants, genetic risk, and incident psoriasis: a large-scale prospective cohort study.

Air pollution and genetic risk have been found to contribute to both onset and development of psoriasis. However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of incident psoriasis remains unknown. Our study aimed to assess the association between joint exposure to multiple air pollutants and the risk of psoriasis and the modification by the genetic susceptibility. This prospective study included 451,064 participants with complete air pollution data and free of psoriasis at baseline from the UK Biobank. All participants were enrolled from 2006 to 2010 and followed up to 2022. The air pollution score (APS) was calculated to assess the joint exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 μm (PM2.5), between 2.5 and 10 μm (PM2.5-10), and ≤ 10 μm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). To evaluate the genetic risk, the polygenic risk score (PRS) for psoriasis was constructed. The Cox proportional hazard models were used to assess the association of air pollution and genetic susceptibility with the risk of psoriasis. Stratified analyses were conducted based on the individual characteristics. During a median follow-up of 13.79 years, 4414 psoriasis events were recorded. The hazard ratios (HRs) [95% confidence intervals (CIs)] for psoriasis were 1.036 (0.936-1.147), 1.091 (0.987-1.206), 1.159 (1.048-1.283), and 1.163 (1.052-1.286) in higher quintile groups compared with the lowest quintile of APS (P trend <0.05). When considering genetic susceptibility, participants with high PRS and high APS had the greatest risk of incident psoriasis [HR (95% CI): 1.962 (1.630-2.362)] than those with low PRS and low APS. The HRs (95% CIs) for PM2.5-10, NOx, PM2.5 absorbance, PM2.5, NO2, and PM10 in the group with high exposure level and genetic risk were 1.831 (1.537-2.181), 1.722 (1.431-2.073), 1.698 (1.416-2.037), 1.619 (1.353-1.938), 1.504 (1.252-1.806), and 1.425 (1.192-1.704), respectively. Long-term exposure to various air pollutants is positively associated with an increased risk of incident psoriasis, particularly in individuals with high genetic risk. More comprehensive measures are needed to reduce the air pollution levels for better prevention of psoriasis.

Demographics, Disease Characteristics, and Time to Effective Treatment of Patients with Psoriasis in the Ghent PsoPlus Cohort of 2021.

Psoriasis is a chronic immune-mediated skin disease with several comorbidities and a considerable influence on quality of life. Many patients with moderate-to-severe psoriasis are undertreated and have a substantial disease duration before effective treatment is started. This study analyzed patient and disease characteristics and time to effective treatment of patients with psoriasis who consulted PsoPlus. It also examined whether a treat-to-target (T2T) approach, which is implemented in PsoPlus, has an impact on treatment choice and disease progression. Through a single center, retrospective study, 170 patients in the PsoPlus dedicated clinic were compared at moment of enrollment in PsoPlus and at the last recorded consultation in 2021. Median disease duration at the first PsoPlus consultation was 16.0 (interquartile range (IQR) 19.0) years. There was a significant difference in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) between the first and the last recorded PsoPlus consultation (PASI 6.0 (IQR 6.4) vs. 0.6 (IQR 2.6); DLQI 11 (IQR 11) vs. 2 (IQR 6); p < 0.001). A weak positive Spearman correlation (rs) was found between disease duration and PASI at the first PsoPlus consultation (rs = 0.175; p = 0.034), while a weak negative correlation (rs = - 0.2; p = 0.013) was found at the last registered PsoPlus consultation. Patients with a disease duration of more than 20years had significantly more switches of treatment than those with a shorter disease duration (p < 0.001). Median time from psoriasis onset until PASI ≤ 2 was 16.0years. Median time from the first PsoPlus consultation until PASI ≤ 2 was 7.0months. The PsoPlus program with its T2T approach effectively improves clinical outcomes and quality of life for patients with psoriasis in a relatively short period, emphasizing the value of a structured, personalized treatment plan for long-term management.

Identification of psoriasis-associated immune marker G3BP2 through single-cell RNA sequencing and meta analysis.

Psoriasis is a chronic skin disease with an increasing prevalence each year. However, the mechanisms underlying its onset and progression remain unclear, and effective therapeutic targets are lacking. Therefore, we employs an innovative approach by combining single-cell RNA sequencing (scRNA-seq) with meta-analysis. This not only elucidates the potential mechanisms of psoriasis at the cellular level but also identifies immunoregulatory marker genes that play a statistically significant role in driving psoriasis progression through comprehensive analysis of multiple datasets. Skin tissue samples from 12 psoriasis patients underwent scRNA-seq, followed by quality control, filtering, PCA dimensionality reduction, and tSNE clustering analysis to identify T cell subtypes and differentially expressed genes (DEGs) in psoriatic skin tissue. Next, three psoriasis datasets were standardised and merged to identify differentially expressed genes (DEGs). Subsequently, weighted gene co-expression network analysis (WGCNA) was applied for clustering analysis of gene co-expression network modules and to assess the correlation between these modules and DEGs. Least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic (ROC) curve analyses were conducted to select disease-specific genes and evaluate their diagnostic value. Single-cell data revealed nine cell types in psoriatic skin tissue, with seven T cell subtypes identified. Intersection analysis identified ADAM8 and G3BP2 as key genes. Through the integration of scRNA-seq and Meta analysis, we identified the immunoregulatory marker gene G3BP2, which is associated with the onset and progression of psoriasis and holds clinical significance. G3BP2 is speculated to promote the development of psoriasis by increasing the proportion of CD8+ T cells.

Psoriatic nail involvement in Malaysia: A 14-year registry review (2007-2020)

Nail psoriasis affects 20% to 30% of psoriasis patients and is an early predictor of psoriatic arthritis (PsA). We evaluated the prevalence, clinical characteristics, and impact on quality of life of patients with nail psoriasis. We conducted a multicenter retrospective cohort study of patients registered with The Malaysian Psoriasis Registry from January 1, 2007 to December 31, 2020. Of the 24,147 patients, 13,081 (54.2%) had nail psoriasis. Patients with nail psoriasis had later onset of psoriasis (34.0 ± 16.6 years vs 32.9 ± 17.6 years, P < .001) and longer disease duration (11.4 ± 10.5 years vs 8.5 ± 9.4 years, P < .01), with a man-to-woman ratio of 1.2:1. They were more likely to have a family history of psoriasis, cardiometabolic diseases, smoking history, higher body mass index, severe disease, PsA, face and scalp involvement, and higher mean Dermatology Life Quality Index scores (9.36 ± 6.84 vs 8.87 ± 6.60). Systemic treatment and biologics were more commonly prescribed in this cohort (25.0% vs 13.2%, P < .001). Overall, 54.2% of the Malaysian Psoriasis Registry patients had nail involvement. Nail psoriasis was associated with longer duration of psoriasis, older age of onset, male sex, and a family history of psoriasis. It proved to be an important predictor for PsA, severe psoriasis, face and scalp involvement, increased cardiometabolic risk, and a greater impairment of quality of life.

Regional variations in psoriatic arthritis: Insights from a nationwide multicenter analysis in Türkiye.

The study aimed to investigate and compare clinical features, disease activity, and the overall disease burden among psoriatic arthritis (PsA) patients across seven distinct geographic regions in Türkiye. A multicenter cross-sectional study involving 1,134 PsA patients from 25 referral centers across seven regions was conducted. Demographic and clinical characteristics, comorbidities, joint involvement, extra-articular manifestations, and disease activity measures were evaluated across regions. A total of 1134 PsA patients from seven different geographic regions in Türkiye participated in this study. The highest number of participants was from the Marmara region (n=409), with subsequent representation from Central Anatolia (n=370), Aegean (n=139), Mediterranean (n=60), Black Sea (n=60), Eastern Anatolia (n=60), and Southeastern Anatolia (n=36) regions. There were significant variations in demographic profile, including age, body mass index, age of disease onset, educational status, comorbidities, and family history of both psoriasis and PsA. Clinical features, such as enthesitis, dactylitis, uveitis, and joint involvement, demonstrated significant variation across regions. Additionally, disease activity measures, including pain, patient and physician global assessments, acute phase reactants, disease activity indices, quality of life, and functional status, displayed considerable regional differences. This nationwide study revealed substantial regional diversity in demographic data, clinical characteristics, disease activity, and quality of life among PsA patients in Türkiye. These findings stress the need to customize treatment approaches to address regional needs and to conduct further research to uncover reasons for disparities. It is crucial to enhance region-specific approaches to improve patient care and outcomes for PsA.

Psoriasis pathogenesis: What’s new in angiogenesis and angiopoietins

Psoriasis is a common chronic inflammatory skin disorder primarily characterized by scaly, erythematous plaques. Microvascular abnormalities are a major pathogenic mechanism, with early histological changes including tortuous dilation of capillaries in the papillary dermis. Increased vascular permeability and angiogenesis nourish proliferative keratinocytes, facilitate inflammatory cell migration, and significantly contribute to the onset and persistence of psoriasis. Angiopoietins, a class of proangiogenic factors, play a significant role in regulating vascular stability, angiogenesis under physiological and pathological conditions, and inflammatory processes. This paper provides a comprehensive review of the advancements in our understanding of angiogenesis and the role of angiopoietins in the context of psoriasis.

Alcohol abuse and discretionary habits in psoriatic patients: impact on IL-17 and IL-23 inhibitor response.

Alcohol abuse is correlated with the onset and worsening of psoriasis, but its effects, as for smoking, on biological therapies are still poorly investigated. This study aimed to determine the prevalence of alcohol abuse and other discretionary habits (such as smoking and sedentary lifestyle) in patients with psoriasis treated with topicals, conventional systemic and biologic therapies. The second objective is to investigate the impact of discretionary habits, focusing on alcohol abuse, on the response to biological therapy. To identify alcohol dependence, the CAGE questionnaire was distributed among patients of our clinic. 305 patients were included with 18% at high risk of alcohol abuse. Clinically, guttate psoriasis and psoriatic arthritis were more common in patients at higher risk of alcohol abuse. Furthermore, patients with an alcohol problem who started biological therapy reported a higher PASI than those who drank less. None of the considered variables seemed to correlate with discontinuation of medication or with lower achievement of the analyzed outcomes (PASI100, PASI90, and PASI≤3). There was a stronger association between alcohol dependence and patients receiving conventional therapy than with patients receiving biologics. The efficacy of biologicals did not seem to be impacted by alcohol consumption, smoking, or sedentary lifestyle.

What Clinical Factors Affect Length of Transition to Psoriatic Arthritis in Patients With Psoriasis?

We aimed to identify clinical and demographic features associated with the interval between psoriasis (PsO) and psoriatic arthritis (PsA). We identified patients with PsO and PsA diagnoses from our tertiary care psoriatic disease biorepository: a longitudinal, real-world database including clinical information and patient-reported outcomes. We used a multivariable a zero-inflated negative binomial model to evaluate several clinical and demographic features that may be associated with the time between PsO and PsA onset. A total of 384 patients were included, of whom 52.2% were female. The mean age of PsO onset was 31.5 years. Advanced age at PsO onset was associated with a shorter interval between PsO and PsA. Based on our model, patients with PsO onset at age 42.6 years (upper end of the interquartile range [IQR]) had a 62% shorter expected interval compared with patients with PsO onset at age 18.9 years (lower end of IQR) (P < 0.001) and were more likely to have concurrent (onset within 6 months) diagnoses (odds ratio 4.56; 95% confidence interval 2.9-7.17). Patients with a body mass index (BMI) of 34 compared with a BMI of 26 had a 10% shorter interval between PsO and PsA, which trended toward statistical significance (P = 0.053). Our study demonstrated that patients with a diagnosis of PsO at an older age have a shorter interval between PsO and PsA diagnoses and are more likely to have concurrent diagnoses compared with patients with an onset of PsO at a younger age. These results suggest that patients with a later onset of PsO may benefit from earlier PsA screening.

Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development.

To assess the potential role of biological treatment for psoriasis (PsO) in reducing the likelihood of psoriatic arthritis (PsA), through a detailed analysis that considered the different historical phases in the PsA management, the different biologics classes, and the different patterns of articular involvement. A monocentric cohort of 1023 PsO patients underwent a rheumatologic assessment in which clinical and therapeutic data were recorded. Chi-squared test and multivariate logistic regression analysis (adjusted for the main PsA risk factors) were performed to compare the likelihood of PsA development in different treatment groups. The PsA prevalence in PsO patients treated at least once with biologics was significantly lower than in patients never treated with biologics (8.9% vs 26.1%, p< 0.001). In multivariate analysis, a significantly (p< 0.01) lower likelihood of PsA development in biologic-treated patients was confirmed in the whole cohort (adjOR 0.228), as well as in the subgroups of patients with PsO onset after 2005 (adjOR 0.264) and after 2014 (adjOR 0.179). Separately analysing the different biologics classes, both the TNF (adjOR 0.206), IL-17 (adjOR 0.051) and IL-23 or 12/23 (adjOR 0.167) inhibitors were significantly (p< 0.01) associated with a lower likelihood of PsA development. Finally, patients treated with biologics had a significantly (p< 0.04) lower prevalence of both pure peripheral PsA (adjOR 0.182) and peripheral PsA with axial involvement (adjOR 0.115). This study provides meaningful and concordant evidence supporting the significant role of different classes of biologics in reducing the likelihood of peripheral and axial PsA development.

Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden.

Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress. The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life. A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (n = 1,669,422). Stress resilience at conscription was estimated using standardized semi-structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new-onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis. Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26-1.36) and 1.23 (95% CI 1.15-1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63-1.98) and 1.53 (1.32-1.77), respectively. This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well-being in the management of psoriasis.

P36 Environmental triggers of psoriasis and relationship to disease severity: insights from the mySkin study

Abstract Introduction and aims Psoriasis is a common debilitating inflammatory skin condition with an established genetic basis. Despite a wealth of genetic research on psoriasis susceptibility, epidemiological studies characterizing environmental triggers of disease onset are limited. Our aim is to identify self-reported triggers of psoriasis onset, and investigate the relationship between triggers and subsequent disease severity. Methods Self-reported data from people with a clinician-confirmed diagnosis of psoriasis were collected through the online mySkin survey. mySkin was launched UK-wide in June 2023 and all surveys completed by 6 December 2023 were analysed. Measures of disease severity at the time of survey completion included Patient Global Assessment and Dermatology Life Quality Index. The association between triggers of psoriasis onset and disease severity was analysed using one-way Anova tests. Results Of 529 participants, 93.4% were of White ethnicity, 64.8% were female and their average age was 51.1 years. Overall, 49.9% reported a family history of psoriasis and 55% (n = 289) of participants reported at least 1 trigger of psoriasis onset. Of those who reported a trigger, the most commonly reported trigger was stress (n = 167, 57.8%), followed by infection (n = 85, 29.4%) and low mood (n = 23, 7.9%). For participants who selected multiple triggers, there was considerable coselection of stress, low mood, climate (pollution, weather) and lifestyle (weight gain, alcohol, smoking) factors. A greater proportion of participants with a family history of psoriasis reported climate and hormonal (pregnancy, childbirth, menopause) triggers of psoriasis onset, compared with those without a family history (73% vs. 26% and 69% vs. 31%, respectively). There was no significant association between triggers of psoriasis onset and disease severity (P = 0.76). Conclusions These self-reported data highlight the importance of stress in psoriasis onset. The co-occurrence of different triggers, including in those with vs. without a family history of psoriasis, underscores the complex aetiology of psoriasis. Further characterization of gene–environment interactions is warranted.

The impact of serum uric acid on psoriasis: NHANES 2005-2014 and Mendelian randomization.

Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, the exact relationship between uric acid levels and psoriasis remains unclear. This study aimed to explore the association between uric acid levels and psoriasis. Observational study participant data (≥16years, n = 23,489) from NHANES 2003-2014. We conducted analyses using a weighted multiple logistic regression model. Genetic data sets for uric acid levels and psoriasis were obtained from the IEU database. We selected genetically independent loci closely associated with serum uric acid levels as instrumental variables and performed Mendelian randomization analyses using five complementary methods: inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. After adjusting for other covariates, the results revealed no significant association between serum uric acid levels and psoriasis (b = 0.999, 95% CI: 0.998, 1.001, p = 0.275). Subgroup analyses stratified by gender and ethnicity showed no significant association between sUA and psoriasis in any of the subgroups. Furthermore, the MR analysis involved the selection of 227 SNPs that were associated with both sUA and psoriasis. IVW results demonstrated no causal relationship between sUA and psoriasis (OR = 0.282, 95% CI: -0.094-0.657, p = 0.142). Our study suggests that uric acid levels are not significantly causally related to psoriasis. This finding provides valuable insights for the treatment and prevention of psoriasis, indicating that merely reducing uric acid levels may not be an effective strategy to reduce the risk of psoriasis onset.

OA09 Significant association between disease duration in axial spondyloarthritis and the occurrence of uveitis and inflammatory bowel disease, with no such association found for psoriasis

Abstract Background/Aims Axial spondyloarthritis is a chronic inflammatory condition primarily impacting the spine and sacroiliac joints. In addition to spinal inflammation and peripheral symptoms, it frequently presents with extra-musculoskeletal manifestations such as inflammatory bowel disease, psoriasis, and anterior uveitis, collectively adding to the overall disease burden. Although existing research has explored the heightened risk of ophthalmological manifestations with prolonged disease duration, there is a paucity of literature examining the association between disease duration in axial spondyloarthritis and the onset of inflammatory bowel disease and psoriasis. Aim: To investigate the relationship between axial spondyloarthritis disease duration and the development of extra-musculoskeletal manifestations. Methods This is a retrospective cohort study with data obtained from the Ankylosing Spondylitis Registry of Ireland (ASRI), which is a large cross-sectional, multicentre cohort study. Using both univariate and multivariate regression analyses, we examined the relationship between axial spondyloarthritis disease duration and extra musculoskeletal manifestations. In the multivariate analysis, several covariates including gender, body mass index, smoking, and HLA-B27 status were considered to account for their potential influence on the observed associations. Results Demographic details were available for 912 patients included at the time of analysis. The median disease duration in years for our cohort was 16. Table 1 presents relevant general characteristics of the ASRI cohort and the results of our regression analysis. Uveitis exhibited a highly significant association (P &amp;lt; 0.001) with AxSpA duration in both univariate and multivariate analyses, even after accounting for covariates. Inflammatory bowel disease also showed a significant association with AxSpA duration in both univariate and multivariate analyses (P &amp;lt; 0.003). In our analysis, psoriasis showed no significant relationship with AxSpA disease duration in both univariate (P = 0.298) and multivariate analyses (P1 = 0.249). Conclusion Our study, using a large data set, reveals distinct patterns of association between axial spondyloarthritis disease duration and inflammatory bowel disease and uveitis. Conversely, psoriasis demonstrates no significant link to disease duration when considering confounding factors. Clinically, these insights are crucial for tailored management strategies, emphasising the need for improved diagnostic time and multidisciplinary care to address the diverse manifestations of AxSpA and optimise patient outcomes. Disclosure B. Dinneen: None. M. Kenyon: None. F. O'Shea: None.

Assessing causal relationships between gut microbiota and psoriasis: evidence from two sample Mendelian randomization analysis

Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001–1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1–1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.

Tobacco smoking negatively influences the achievement of greater than three-quarters reduction in psoriasis area and severity index after eight weeks of treatment among patients with psoriasis: Findings from a prospective study.

Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China. Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI75) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4. A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9-16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI75 at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI75 achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91-18.89), 14.14 (95% CI: 8.27-24.20), and 3.05 (95% CI: 1.20-7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI75 achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI75 achievement. Tobacco smoking was negatively associated with PASI75 achievement both in current and former smokers, and former smokers had higher PASI75 achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses.

PSORIASIS AND MENTAL HEALTH: A PSYCHODERMATOLOGICAL APPROACH WITH AN EMPHASIS ON PSYCHOTHERAPY.

Psoriasis is a multifactorial, inflammatory, chronic disease caused by the complex interaction of genetic and environmental factors, including psychosocial distress. This review reasons the importance of the biopsychosocial model and why it should be considered when treating patients with psoriasis. We aimed to provide current evidence for the psychological etiopathogenesis, psychosocial comorbidities, psychosocial assessment, and psychological therapeutic interventions in psoriasis. The main pathways linking stress to psoriasis involve the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, peripheral nervous system, and immune system. Fear of embarrassment and social stigma is reported to be one of the main stressful factors in the onset or worsening of psoriasis. Mental disorders are the most common comorbidity in psoriatic patients, but they are still often overlooked and undertreated. Previous research has shown increased rates of sleep disorders, depression, anxiety, borderline personality disorder, and alcohol use disorder. Biological treatment of psoriasis could reduce symptoms of depression, anxiety, and insomnia in patients with psoriasis. According to research, psoriasis patients may have certain psychological characteristics, including type D personality, alexithymia, high vulnerability to stress, and escape-avoidance coping strategy. Mental and social health should be part of psoriasis severity assessment, especially in patients who carry an increased risk of mental illness. Cognitive behavioral therapy, mindfulness-based cognitive therapy, and relaxation therapy could be used to decrease psoriasis severity and improve the quality of life of psoriasis patients. Psychoanalytic evaluation can contribute to dermatologic practice by typifying unconscious conflicts, detecting the defense mechanisms for stress coping, and choosing the treatment on unconscious preferences. The collaboration between the dermatologist, family medicine specialist, psychologist, and psychiatrist can help to break the psychosomatic and somatopsychic vicious circles.