Psoriatic arthritis (PsA) involves intricate immune-mediated pathways that extend beyond the well-characterized IL-23/IL-17 axis. Given that many patients show inadequate responses to current therapies, identifying novel immune drivers is essential. To clarify how specific immune cell populations influence PsA susceptibility, we performed a bidirectional two-sample Mendelian randomization (MR) study. We used genetic instruments for immune traits from a GWAS of 3,757 European individuals and PsA summary data from the IEU database (5,065 cases and 21,286 controls). Applying inverse variance weighting as our principal method. At a nominal significance level (P < 0.05), we detected 14 immune phenotypes linked to heightened risk and 12 associated with reduced risk. Among the risk-associated phenotypes, activated B cells-particularly those expressing CD25 and BAFF-R on IgD+CD24+ subsets-emerged as prominent markers, a finding that shifts focus toward humoral involvement alongside the conventional emphasis on T cells alone. We also identified pathogenic contributions from specific T cell subsets, notably CCR7+naïve CD4+T cells and CD127+CD45RA+CD4+T cells. Conversely, certain natural killer T cell phenotypes appeared protective, hinting at a regulatory role for these populations. Reverse MR indicated that PsA liability itself may drive changes in 23 immune phenotypes, including depletion of circulating plasmacytoid dendritic cells and alterations in myeloid compartments-patterns likely reflecting cellular migration into inflamed synovial tissue. Importantly, none of these associations survived false discovery rate correction, indicating that these findings are exploratory. Our findings map the genetic underpinnings of immune dysregulation in PsA and provide a hypothesis-generating resource for therapeutic strategies targeting B cell stimulation. The preliminary nature and uncertainty of these associations necessitates further investigation and validation in independent, larger cohorts alongside current cytokine-directed approaches.

Genetic susceptibility to psoriasis involves multiple loci, including TYK2 (Tyrosine Kinase 2), which is associated with various autoimmune diseases. However, its specific role and mechanisms in psoriasis remain unclear. This study aimed to identify psoriasis-associated proteins using Summary-based Mendelian Randomization (SMR) and to explore their regulatory mechanisms. SMR analysis integrating pQTL data was conducted to identify proteins linked to psoriasis, revealing ICAM1 (Intercellular Adhesion Molecule 1) as a potential pathogenic factor. A key SNP, rs34536443 (P1104A), located in TYK2, was found to regulate ICAM1. To assess its function, THP-1 cells carrying the TYK2-P1104A mutation were generated, and ICAM1 and cytokine expression were analyzed following LPS stimulation. The effect of the TYK2 inhibitor Deucravacitinib was tested in an imiquimod (IMQ)-induced psoriasis mouse model. SMR identified ICAM1 as a causal protein for psoriasis, regulated by the TYK2 SNP rs34536443. In TYK2-P1104A mutant THP-1 cells, LPS-induced ICAM1 expression was significantly reduced, with ICAM5 unaffected. The mutation also suppressed IL-1β, TNF-α, IL-6, and IL-18 expression, suggesting anti-inflammatory effects. Single-cell RNA-seq revealed enrichment of TYK2, ICAM1, and ICAM5 in dendritic cells and monocytes. In vivo, Deucravacitinib significantly downregulated ICAM1 in the IMQ-induced psoriasis model, with minimal effect on ICAM5. This study identifies ICAM1 as a key mediator in psoriasis via SMR analysis and implicates the TYK2 SNP rs34536443 in its regulation. The TYK2-P1104A variant attenuates ICAM1 and cytokine expression, and Deucravacitinib downregulates ICAM1 in vivo. These findings provide mechanistic insights into the TYK2-ICAM1 axis and support the therapeutic potential of TYK2 inhibitors for psoriasis.

The management of psoriasis has undergone substantial evolution; however, the long-term prescription trends remain ambiguous. This study utilised a comprehensive data set of psoriasis drug prescriptions in Germany from 2010 to 2022, with the objective of evaluating the evolution of treatment modalities over time. A retrospective longitudinal claims data analysis on systemic biologicals, non-biologicals, and topical treatments for psoriasis was conducted covering prescription rates, medical costs from the payer's perspective, and defined daily doses (DDDs). Psoriasis prevalence increased slightly from 2.6% in 2010 to 2.7% in 2022. During this period, the proportion of persons receiving prescriptions rose from 55.0% in 2010 to 57.4% in 2022. By 2022, 46.2% of these persons received topical treatments, 13.0% systemic glucocorticosteroids (SCS), 6.7% non-biologicals, and 6.2% biologicals. Compared to 2010, the use of biologicals increased by 449.8%, SCS by 12.6%, non-biologicals by 13.9%, while topical treatments decreased by 3.2%. The annual cost per person treated with a biologic decreased from €16,315 to €13,412, while non-biologic and topical therapy costs increased slightly. Adalimumab was the most frequently prescribed systemic drug, followed by ustekinumab and secukinumab. The highest mean costs per-person were for ustekinumab (€19,717) and risankizumab (€16,986). In more than a decade, the use of innovative systemic drugs, especially biologicals, in Germany has increased substantially. Despite their high cost, biologic expenses per person have slightly decreased over time.

Psoriasis significantly impacts patients' mental health and social relationships, often leading to feelings of stigmatization and shame due to the visibility of skin lesions. This study aimed to identify factors influencing the quality of life in patients with psoriasis. A cross-sectional study was conducted from November 2018 to December 2020, involving 100 patients treated for psoriasis. The research utilized the WHO Quality of Life Questionnaire (WHOQoL-Bref), the Psoriasis Area and Severity Index (PASI), the Acceptance of Illness Scale (AIS), the Hospital Anxiety and Depression Scale (HADS), and the Mini Nutritional Assessment (MNA). The analysis included demographic, clinical, and psychological variables to evaluate their impact on quality of life. The multivariate linear regression model revealed that significant independent predictors of quality of life included age (p=0.001), duration of disease (p=0.004), and nutritional status (p=0.002). In the physical domain, factors such as phototherapy (r=2.46) and anxiety levels assessed by the HADS anxiety subscale (r=-0.23) were particularly relevant. In the psychological domain, the presence of psoriatic arthritis (r=1.978), hand and foot psoriasis (r=2.34), and scores on the HADS anxiety (r=-0.212) and depression subscales (r=-0.226) were significant. Male gender (r=1.632) and depressive symptoms (r=-0.352) impacted the social domain. In the environmental domain, predictors included erythrodermic psoriasis (r=1.98), hand and foot psoriasis (r=2.312), phototherapy (r=1.877), PASI score (r=-0.04), and depression as measured by HADS (r=-0.228). The primary predictors of quality of life in patients with psoriasis are the type of psoriasis, the presence of anxiety and depressive disorders, and treatment with phototherapy. However, the study's single-center design and relatively small sample size may limit the generalizability of the findings. Further multi-center studies are needed to confirm these results and broaden their applicability.

Patients' treatment expectations significantly influence the effectiveness of medical and pharmacological treatments. This clinical proof-of-concept study aimed to enhance treatment outcomes by targeting positive treatment expectations of psoriasis patients beginning systemic anti-psoriatic therapy with secukinumab, an interleukin (IL)-17A antagonist. We randomly assigned patients to three groups: a treatment as usual (TAU) group receiving the standard 300mg dose of secukinumab, a dose-control (DC) group with 75% dose reduction and an experimental (EXP) group receiving the same reduced dose along with a "cover story" designed to positively influence treatment expectations. We evaluated skin symptoms using the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index (DLQI), perceived itch, mood and plasma IL-17A levels at baseline and at 1, 2, 3, 4, 8, 12, and 16weeks post intervention. The study included N = 120 patients (average age = 45.78 years, 34% female). A high baseline expectation level (8.1 of 10 points) was observed across all groups which could not be further increased by the EXP-group's "cover story". The EXP and DC groups did not differ with regard to reaching 75% improvement in PASI scores (PASI75), a DLQI score of 0 or 1 or at least 4 points improvement in itch. Over time, the EXP-group showed a faster decline in PASI scores and anxiety symptoms compared to the DC-group, but less improvement in quality of life. IL-17A levels significantly increased throughout the treatment, with no significant differences between groups despite the 75% dose reduction. This study demonstrates an attempt to modify patients' treatment expectations to enhance the effectiveness of pharmacological therapy with secukinumab in psoriasis patients. However, verbal suggestion alone did not significantly improve clinical outcomes, suggesting that future studies should explore alternative approaches to leverage placebo effects to the benefit of patients with psoriasis.

Psoriasis is a chronic, immunologically mediated disease of multifactorial origin, with genes playing a key role and environmental factors, such as infections, often triggering its onset or exacerbation. While acute streptococcal infections are commonly linked to guttate psoriasis, viral and fungal infections have also been associated with psoriasis flares. We report a case of severe psoriasis exacerbation during viral parotitis caused by paramyxovirus in a 49-year-old male patient with a long-standing psoriasis diagnosis. Following successful treatment with secukinumab, the patient experienced a flare-up coinciding with symptoms of mumps infection. Serological tests confirmed the presence of mumps virus RNA. Secukinumab was discontinued, and treatment with risankizumab resulted in rapid remission of psoriasis. While paramyxovirus infections are not typically associated with psoriasis flares, emerging evidence suggests that dysregulated antiviral immune responses may induce IL-23 production, possibly contributing to inflammation in psoriasis. This case highlights the need for further research on the role of antiviral immune responses in psoriasis exacerbations and the potential therapeutic implications of targeting the IL-23 pathway.

Acrodermatitis enteropathica (AE) can be caused by inherited or acquired zinc deficiency, among which site-specific skin lesions or even psoriasiform skin manifestations are present. Few cases exist in the literature involving the diagnosis and treatment of AE overlapped with psoriasiform lesions. In this case, we reported a teenage boy presented characteristic site-specific skin lesions of AE with low serum zinc level, subsequently progressed into generalized pustular psoriasiform manifestations under a genetic background, while a rapid recovery was observed after monotherapy of zinc supplementation. Since zinc malabsorption was suspend to be the trigger of both AE and psoriasiform lesions, simply maintaining balanced zinc homeostasis might be a safe and effective treatment for the overlapped manifestations.

Psoriasis is a chronic, inflammatory, immune-mediated skin disease that has significant impact on a patient's quality of life, yet it remains challenging for dermatologists to successfully identify and manage. Without effective screening, diagnosis and treatments, psoriasis can potentially progress to psoriatic arthritis. A descriptive, observational cross-sectional study of Saudi Arabian dermatologists and patients with psoriasis was conducted to explore dermatologist and patient perspectives of psoriasis, including diagnosis, management, disease course and unmet needs. This study involved a quantitative questionnaire administered to 31 dermatologists and 90 patients with psoriasis at eight medical centers and was analyzed using descriptive statistics. Dermatologists and patients perceived that psoriasis treatment was initiated promptly and that follow-up visits were sufficient. Their perspectives differed in the time to diagnosis and patient reaction, symptom severity, input into treatment goals and educational needs. The dermatologists' concerns about underdiagnosed psoriasis (13%) were primarily related to patient awareness (87%), physician awareness (58%), and the absence of a regular screening program (52%). Only 31% of patients with psoriasis were highly satisfied with their psoriasis treatment, with 78% experiencing unpleasant symptoms of pain or swelling in joints indicative of psoriatic arthritis. However, only 56% of these patients reported these symptoms to their physicians. When dermatologists were made aware of this difference, referrals to a rheumatologist increased. The study highlights the importance of strengthening psoriasis management by enhancing dermatologist referral and screening practices, adopting a multidisciplinary approach to care, and improving education and resources for physicians and patients. These results can help to inform the improvement of psoriasis screening, diagnosis and treatment strategies and ensure that expectations meet treatment outcomes. Further research exploring the dermatologist and patient perspectives of the disease pathway from psoriasis to psoriatic arthritis and tailor-made treatment approaches is recommended.

Psoriasis is a prevalent inflammatory skin disorder that is associated with a number of comorbidities including cardiovascular disease and metabolic syndrome. Exercise can influence the outcomes of chronic inflammatory diseases, and the presence of these diseases can also influence physical activity in afflicted patients. We reviewed the available literature published on exercise in psoriasis patients and aimed to explore physical activity levels, barriers to exercise, physical fitness, exercise as a prevention strategy as well as a treatment modality. Overall, patients with moderate to severe psoriasis are more sedentary than the general population and experience barriers to exercise secondary to their skin disease. Moderate to vigorous exercise may be an independent preventative factor in reducing the incident risk of developing psoriasis and the utilization of exercise as a weight loss strategy may improve disease severity especially in overweight patients. Expert panels agree that exercise can be beneficial as an adjunct treatment in patients with psoriasis who are overweight; however, more randomized clinical trials are needed to establish these links.

PurposeBoth brodalumab and guselkumab improve skin clearance in patients with moderate-to-severe plaque psoriasis after inadequate response to ustekinumab. In the absence of a direct head-to-head comparison, the relative efficacy of brodalumab and guselkumab in non-responders to ustekinumab were compared using a matching-adjusted indirect comparison (MAIC).Patients and MethodsIndividual patient data for brodalumab (n = 121) were pooled from the AMAGINE-2 and -3 trials and adjusted using a propensity score reweighting method, so that baseline and week 16 characteristics matched the aggregate published data of patients with an inadequate response to ustekinumab who switched to guselkumab (n = 135) in the NAVIGATE trial.ResultsAfter inadequate response to ustekinumab, brodalumab resulted in significantly higher psoriasis area and severity index (PASI) 90 rates versus guselkumab at post-treatment switch week 12 (62.7% vs 48.1%, relative difference 14.6% [95% confidence interval [CI] 5.3–23.9], p = 0.002 [number needed to treat [NNT] = 6.8]) and week 36 (63.7% vs 51.1%; relative difference 12.6% [95% CI 4.1–21.0]; p = 0.004 [NNT = 7.9]) and PASI 100 rate at week 36 (40.3% vs 20.0%; relative difference 20.3% [95% CI 11.8–28.7]; p < 0.001 [NNT = 4.9]).ConclusionIn this MAIC, brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab. Switching to brodalumab in such patients may be a more effective strategy than switching to guselkumab.