UNASSIGNED: Psoriasis is a common autoimmune disease in clinical practice, and previous observational studies have suggested that PPARG agonists such as Pioglitazone may be potential therapeutic agents. However, due to interference from various confounding factors, different observational studies have not reached a unified conclusion. We aim to evaluate the potential use of PPARG agonists for treating psoriasis from a new perspective through drug-targeted Mendelian randomization (MR) analysis.
UNASSIGNED: This study includes data on 8,876 individuals for acute myocardial infarction from GWAS, and LDL cholesterol data from 343,621 Europeans. FinnGen contributed psoriasis vulgaris data for 403,972 individuals. The DrugBank10 databases function to identify genes encoding protein products targeted by active constituents of lipid-modifying targets. A two-sample MR analysis and summary-data-based MR (SMR) analysis estimated the associations between expressions of drug target genes and symptoms of psoriasis vulgaris. A multivariable MR study was further conducted to examine if the observed association was direct association.
UNASSIGNED: SMR analysis revealed that enhanced PPARG gene expression in the blood (equivalent to a one standard deviation increase) was a protective factor for psoriasis vulgaris (beta = -0.2017, se = 0.0723, p = 0.0053). Besides, there exists an MR association between LDL mediated by PPARG and psoriasis vulgaris outcomes (beta = -3.9169, se = 0.5676, p = 5.17E-12). These results indicate that PPARG is a therapeutic target for psoriasis, suggesting that psoriasis may be a potential indication for PPARG agonists.
UNASSIGNED: This study confirms that therapeutic activation of PPARG helps suppress the development of psoriasis. Psoriasis may be a new indication for PPARG agonists, such as Pioglitazone. In the future, new anti-psoriatic drugs could be developed targeting PPARG.

BACKGROUND: Prior research has explored the relationship between inflammatory skin disorders and breast cancer (BC), yet the causality of this association remains uncertain.
METHODS: Utilizing a bidirectional two-sample Mendelian randomization (MR) approach, this study aimed to elucidate the causal dynamics between various inflammatory skin conditions-namely acne, atopic dermatitis, psoriasis vulgaris, urticaria, and rosacea-and BC. Genetic variants implicated in these disorders were sourced from comprehensive genome-wide association studies representative of European ancestry. In the forward MR, BC was posited as the exposure, while the reverse MR treated each inflammatory skin disease as the exposure. A suite of analytical methodologies, including random effects inverse variance weighted (IVW), weighted median (WME), and MR-Egger, were employed to probe the causative links between inflammatory skin diseases and BC. Sensitivity analyses, alongside evaluations for heterogeneity and pleiotropy, were conducted to substantiate the findings.
RESULTS: The MR analysis revealed an increased risk of acne associated with BC (IVW: OR = 1.063, 95% CI = 1.011-1.117, p = 0.016), while noting a decreased risk of atopic dermatitis (AD) in BC patients (IVW: OR = 0.941, 95% CI = 0.886-0.999, p = 0.047). No significant associations were observed between BC and psoriasis vulgaris, urticaria, or rosacea. Conversely, reverse MR analyses detected no effect of BC on the incidence of inflammatory skin diseases. The absence of pleiotropy and the consistency of these outcomes strengthen the study\'s conclusions.
CONCLUSIONS: Findings indicate an elevated incidence of acne and a reduced incidence of AD in individuals with BC within the European population.

Psoriasis vulgaris (PV) is a disease characterized by skin manifestations and systemic inflammation. There are no published studies to date on vitamin K status assessed by extrahepatic vitamin K-dependent proteins [e.g., osteocalcin (OC) and matrix Gla protein (MGP)] in patients with PV, even if vitamin K was found to promote wound contraction and decrease the healing time of the skin. Metabolic syndrome (MS), a comorbidity of PV, was found to influence vitamin K status, and vitamin D was found to be involved in the pathogenesis of PV. Therefore, our aim was to assess the status of vitamins K and D in subjects with PV. We enrolled 44 patients with PV and 44 age- and sex-matched subjects as a control group (CG), of which individuals with MS were designated the CG with MS subgroup. Furthermore, the PV patients were stratified into two subgroups: those with MS (n = 20) and those without MS (n = 24). In addition to the quantification of vitamin D and MGP in all subjects, the uncarboxylated OC/carboxylated OC (ucOC/cOC) ratio was also assessed as an inversely proportional marker of vitamin K status. We found an increased ucOC/cOC ratio in the PV group compared to CG but also a greater ucOC/cOC ratio in the PV with MS subgroup than in the CG with MS subgroup. MGP was decreased in the PV with MS subgroup compared to CG with MS subgroup. There was no difference in the vitamin D concentration between the groups. This is the first study to report decreased vitamin K status in patients with PV, independent of the presence of MS.

UNASSIGNED: Biologics have revolutionized psoriasis treatment; however, relapse of psoriasis after discontinuation of biologics remains unresolved.
UNASSIGNED: To assess the impact of adjunctive Chinese medicine (CM) therapy on relapse of psoriasis vulgaris (PV) after discontinuation of biologics.
UNASSIGNED: We constructed a prospective cohort study through a psoriasis case registry platform that enrolled patients treated with biologics (in combination with or without CM). The endpoint event was relapse, defined as loss of psoriasis area and severity index (PASI) 75.
UNASSIGNED: A total of 391 patients completed the study and were included in the analysis, of whom 169 (43.2%) experienced relapse during follow-up. To minimize the bias, a 1:1 propensity score matching (PSM) was performed, generating matched cohorts of 156 individuals per group. Adjuvant CM therapy significantly associated with reduced incidence of relapse (HR =0.418, 95% CI = 0.289 ∼ 0.604, p < 0.001), and the protective effect of CM in the subgroup analysis was significant. In addition, PASI 90 response and disease duration were associated with relapse (p < 0.05).
UNASSIGNED: Adjunctive CM therapy is associated with reduced relapse incidence in PV after discontinuation of biologics.

BACKGROUND: Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence.
METHODS: Our analysis utilized 15 genome-wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two-sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p-values using the Benjamini-Hochberg method.
RESULTS: Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed-up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris.
CONCLUSIONS: Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed-up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.

BACKGROUND: Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are complex, multifactorial diseases significantly impacting health and quality of life. Predicting treatment response and disease progression is crucial for optimizing therapeutic interventions, yet challenging. Automated machine learning (AutoML) technology shows promise for rapidly creating accurate predictive models based on patient features and treatment data.
OBJECTIVE: This study aims to develop highly accurate machine learning (ML) models using AutoML to address key clinical questions for PsV and PsA patients, including predicting therapy changes, identifying reasons for therapy changes, and factors influencing skin lesion progression or an abnormal Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score.
METHODS: Clinical study data from 309 PsV and PsA patients were extensively prepared and analyzed using AutoML to build and select the most accurate predictive models for each variable of interest.
RESULTS: Therapy change at 24 weeks follow-up was modeled using the extreme gradient boosted trees classifier with early stopping (area under the receiver operating characteristic curve [AUC] of 0.9078 and logarithmic loss [LogLoss] of 0.3955 for the holdout partition). Key influencing factors included the initial systemic therapeutic agent, the Classification Criteria for Psoriatic Arthritis score at baseline, and changes in quality of life. An average blender incorporating three models (gradient boosted trees classifier, ExtraTrees classifier, and Eureqa generalized additive model classifier) with an AUC of 0.8750 and LogLoss of 0.4603 was used to predict therapy changes for 2 hypothetical patients, highlighting the significance of these factors. Treatments such as methotrexate or specific biologicals showed a lower propensity for change. An average blender of a random forest classifier, an extreme gradient boosted trees classifier, and a Eureqa classifier (AUC of 0.9241 and LogLoss of 0.4498) was used to estimate PASI (Psoriasis Area and Severity Index) change after 24 weeks. Primary predictors included the initial PASI score, change in pruritus levels, and change in therapy. A lower initial PASI score and consistently low pruritus were associated with better outcomes. BASDAI classification at onset was analyzed using an average blender of a Eureqa generalized additive model classifier, an extreme gradient boosted trees classifier with early stopping, and a dropout additive regression trees classifier with an AUC of 0.8274 and LogLoss of 0.5037. Influential factors included initial pain, disease activity, and Hospital Anxiety and Depression Scale scores for depression and anxiety. Increased pain, disease activity, and psychological distress generally led to higher BASDAI scores.
CONCLUSIONS: The practical implications of these models for clinical decision-making in PsV and PsA can guide early investigation and treatment, contributing to improved patient outcomes.

The association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown.
To investigate whether there is a causal effect between psoriasis vulgaris and BP.
Two-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and \"leave-one-out\" sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively.
Genetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, P= 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one-out sensitivity analysis.
Our results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted.

BACKGROUND: Several studies have reported the association between pure hypercholesterolemia (PH) and psoriasis, but the causal effect remains unclear.
METHODS: We explored the causal effect between PH and psoriasis using two-sample bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies. Single nucleotide polymorphisms related with exposures at the genome-wide significance level (p < 5×10-8 ) and less than the linkage disequilibrium level (r2  < 0.001) were chosen as instrumental variables. Subsequently, we used inverse variance weighting (IVW), MR-Egger and weighted median (WM) methods for causal inference. p < 0.05 was considered statistically significant. Heterogeneity was tested using Cochran\'s Q-test, and horizontal pleiotropy was examined using the MR-Egger intercept. Leave-one-out analyses were performed to assess the robustness and reliability of the results.
RESULTS: MR results showed a positive causal effect of PH on psoriasis [IVW: odds ratios (OR): 1.139, p = 0.032; MR-Egger: OR: 1.434, p = 0.035; WM: OR: 1.170, p = 0.045] and psoriatic arthritis (PsA) (IVW: OR: 1.210, p = 0.049; MR-Egger regression: OR: 1.796, p = 0.033; WM: OR: 1.317, p = 0.028). However, there is no causal relationship between PH and psoriasis vulgaris as well as other unspecified psoriasis. Inverse MR results suggested a negative causal relationship between PsA and PH (IVW: OR: 0.950, p = 0.037). No heterogeneity and horizontal pleiotropy exist, and these results were confirmed to be robust.
CONCLUSIONS: PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.

OBJECTIVE: Psoriasis is a chronic, non-contagious autoimmune condition marked by dry, itchy,erythematous and scaly plaques. From modest, localized plaques to total body coverage, the severity of psoriasis varies. Plaque, guttate, inverted, pustular, and erythrodermic psoriasis are the five primary kinds. About 90% of cases are of plaque psoriasis, commonly known as psoriasis vulgaris. Study aims to determine the impact of an rs2228570 (FokI) variant and an rs11568820 (CDX2) variant on serum vitamin D levels (SVD) in patients with psoriasis, and the correlation between the two variants and disease severity.
METHODS: A case-control study consisting of 95 psoriasis vulgaris patients and 84 healthy controls. The clinical investigation, molecular genetics analysis, and biochemical analysis were done for both groups.
RESULTS: SVD levels were significantly decreased in psoriasis patients group. FokI genotypes analysis, we found no significant variance between groups. CDX2 G/G genotype is more prevalent in patients than controls. Moderate psoriasis vulgaris patients with CDX2 G/G genotypes have higher SVD levels than CDX2 G/A, and CDX2 A/A p = 0.003.
CONCLUSIONS: The study found a difference in vitamin D levels between patients and healthy subjects, as well as a difference in vitamin D levels with different FoKI and CDX2 genotypes.

Of those patients diagnosed with generalized pustular psoriasis (GPP) in Japan, approximately 30% have a prior psoriasis vulgaris (PsV) diagnosis. Therefore, understanding factors associated with a GPP diagnosis is essential for early diagnosis of GPP in patients with PsV. This retrospective cohort study was conducted to identify associated factors for GPP diagnosis in patients with PsV. Eligible patients with two confirmed diagnoses of PsV with/without a confirmed GPP diagnosis (International Classification of Disease 10th revision codes L40.0 and L40.1, respectively) were identified from the Japanese Medical Data Center database (JMDC) (July 1, 2005-January 31, 2019). Weighted logistic regression was used to identify associated factors (based on recorded comorbidities) between the PsV only and PsV with GPP cohorts. Odds ratios (ORs) of ≥1.5, associated with a high probability of a GPP diagnosis, were reported for factors with ≥5 patients/cohort. The time from event to GPP diagnosis was evaluated. The highest associated factor for GPP diagnosis was psoriatic arthritis (OR 20.2, 95% confidence interval [CI] 17.06-23.92, P < 0.0001), which also had the shortest time from event to GPP diagnosis (median 119 days). Other comorbidities associated with GPP diagnosis were other psoriasis, tonsillitis, and sinusitis. Treatments associated with GPP diagnosis included systemic corticosteroids (OR 2.19, 95% CI 1.98-2.43, P < 0.0001; median time from treatment initiation to GPP diagnosis 180 days). Other associated treatments (other immunosuppressants, interleukin [IL]-17 or IL-23 inhibitors, and phototherapy) had a delay of ≥1 year from treatment initiation to GPP diagnosis. Back pain, headache, and fever were also identified as associated with a GPP diagnosis. Patients with PsV requiring systemic therapies are more likely to receive a GPP diagnosis than those not requiring systemic treatment. These data will help identify patients with PsV at high risk of developing GPP and potentially support early GPP diagnosis.