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Despite observational studies suggesting a link between psoriatic disease (including psoriasis and psoriatic arthritis) and migraine, it is unclear whether there is a shared genetic etiology or a causal relationship between the two conditions. We aimed to reveal the genetic overlap and causality using the Mendelian randomization (MR) framework. The genetic analysis utilized summary data from the most extensive European genome-wide association study (GWAS) of migraine. Well-powered psoriatic disease GWAS data were obtained from two independent cohort studies, which served as discovery and validation datasets. Global and regional genetic correlations between psoriatic disease and migraine were assessed, and pleiotropic regions identified by pairwise GWAS analysis were further annotated. We further applied a two-sample MR multivariate MR to investigate the potential causal relationship between them. The global genetic correlation test indicated weak correlations between psoriatic disease and migraine, while regional correlation analyses delineated one significant shared locus between psoriasis and migraine. Pathway enrichment analysis revealed that shared genes were involved biological processes to the major histocompatibility and antigen processing and presentation. In terms of causality estimates, genetically predicted psoriasis (Pmeta = 0.003) and psoriatic arthritis (Pmeta = 0.028) were associated with an increased risk of migraine. Multivariate MR analysis indicated that psoriasis was an independent risk factor for migraine (P < 0.05). No significant associations were found in the reverse direction. Our study supported the causal role of psoriasis on migraine, and the central role for immunomodulatory etiology. These findings have significant implications for the management of migraine and clinical practice in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Psoriatic disease (PsD) is a chronic disease affecting skin (psoriasis) and joints (psoriatic arthritis, PsA) that has a significant impact on patients' quality of life (QOL). We report findings from the Japanese subgroup of patients included in Psoriasis and Beyond: The Global Psoriatic Disease Survey, a cross‐sectional, quantitative online survey of patients with self‐reported, healthcare professional (HCP)‐diagnosed, moderate‐to‐severe plaque psoriasis, with or without PsA. Eligible patients who were recruited online completed a 25‐min internet‐based survey in Japanese. We assessed patients' understanding of the systemic nature of PsD, disease burden, perception towards their HCPs, treatment expectations, and satisfaction with care. Of the 148 patients, 74% were females. In total, 65% of patients were aware of the systemic nature of their disease. A minority of patients (27%) were aware that PsA was related to their psoriasis, and 30% and 42% of patients were unaware of any manifestations and comorbidities, respectively, related to PsD. Overall, 21% of patients reported that their disease has a "very large" to "extremely large" impact on their QOL (assessed by Dermatology Life Quality Index score), while the majority (61%) reported a "small" effect or "no effect" at all on QOL. Patients experienced stigma and discrimination and had a negative impact on relationships due to PsD. More patients with psoriasis and concomitant PsA (66%) were satisfied with their current treatment than those with psoriasis alone (46%). Overall, 41% of patients were not involved in deciding their treatment goals. These results suggest that Japanese patients may not be fully aware of the systemic nature of PsD, its manifestations and comorbidities. While these patients were somewhat satisfied with their current treatment, they were only occasionally consulted in deciding treatment goals. Policy measures are required to address the stigma and discrimination experienced by patients. Increased patient participation in their care supports shared decision‐making and enhanced treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the psoriatic disease risk among patients with previous appendicitis. Methods: This study was a nationwide population‐based case–control study about the association between the psoriatic disease risk among patients with a history of appendicitis in Taiwan. The study population consisted of newly diagnosed psoriatic disease with at least two outpatient visits, and the control group included those patients without psoriatic disease at the same index date. Patients with a previous diagnosis of appendicitis or who underwent appendectomy surgery prior to their psoriatic disease diagnosis were recorded. The odds ratio of psoriatic disease diagnosis in the two groups with and without a history of appendicitis were analyzed and compared. Results: A total of 48 894 individuals diagnosed with psoriatic disease were matched with 292 656 controls by age and gender. Notably, the proportion of patients with a history of appendicitis or primary appendectomy was significantly elevated among those with psoriatic disease compared with the control cohort (both p <.05). On average, the occurrence of appendicitis preceded the index date by 3.3 ± 2.3 years. Multivariate analysis revealed a heightened incidence rate of psoriatic disease in patients previously diagnosed with appendicitis, periodontal disease, Charlson comorbidity index score (CCIS) ≧1, and ill‐defined intestinal infections. This association persisted after adjusting for confounding factors, such as periodontal disease, CCIS, Salmonella, and ill‐defined intestinal infections. The odds ratios for psoriatic disease in individuals with a history of appendicitis, periodontal disease, CCIS ≧1, and ill‐defined intestinal infections were 1.16, 1.008, 1.69, and 1.23, respectively, with corresponding 95% confidence intervals of 1.03–1.31, 1.05–1.11, 1.65–1.74, and 1.20–1.26. These findings underscore the independent association between appendicitis and subsequent development of psoriatic disease, even after adjusting for relevant comorbidities and potential confounders. Conclusion: Our research illustrates that appendicitis is associated with an increased likelihood of developing a psoriatic disease, despite several limitations. These limitations encompass variables such as dietary and smoking habits, alongside other potential confounding factors that were not fully considered. Moreover, inherent biases in utilizing national health insurance data, such as the absence of laboratory information, as well as the constraints inherent in a retrospective study design, should be acknowledged. [ABSTRACT FROM AUTHOR]

Psoriatic disease, encompassing both psoriasis (Pso) and psoriatic arthritis (PsA), is closely intertwined with a significantly elevated risk of developing cardiovascular diseases. This connection is further compounded by a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, obesity, insulin resistance, arterial hypertension, and dysregulated lipid profiles. These comorbidities exceed the rates seen in the general population and compound the potential for increased mortality among those living with this condition. Recognizing the heightened cardiometabolic risk inherent in psoriatic disease necessitates a fundamental shift in the treatment paradigm. It is no longer sufficient to focus solely on mitigating inflammation. Instead, there is an urgent need to address and effectively manage the metabolic parameters that have a substantial impact on cardiovascular health. Within this context, apremilast emerges as a pivotal treatment option for psoriatic disease. What sets apremilast apart is its dual-action potential, addressing not only inflammation but also the critical metabolic parameters. This comprehensive treatment approach opens up new opportunities to improve the well-being of people living with psoriatic disease. This review delves into the multifaceted aspects involved in the development of cardiovascular disease and its intricate association with psoriatic disease. We then provide an in-depth exploration of the pleiotropic effects of apremilast, highlighting its potential to simultaneously mitigate metabolic complications and inflammation in individuals affected by these conditions. [ABSTRACT FROM AUTHOR]

Introduction: Circulating T follicular helper (cTfh) cells and circulating T peripheral helper (cTph) cells (which share common characteristics with the cTfh population) are implicated in the pathogenesis of immune-mediated and autoimmune diseases such as psoriasis (Ps). Their close interplay with the interleukin 17 (IL-17) axis and the ex vivo effect of IL-17-targeting biologic agents used to treat Ps on them are elusive. This study aimed to investigate the effect of biologics targeting IL-17 on cTfh and cTph cell subpopulations isolated from the blood of patients with Ps. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with Ps at treatment initiation and three months later. Samples were also collected from controls. Cells were stained using monoclonal antibodies. Flow cytometry assessed the fraction of cTfh (CD3+CD4+CXCR5+) and cTph (CD3+CD4+CXCR5-PD-1hi) cells.. Results: Flow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS+ and ICOS+ PD-1+ expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS+ and ICOS+ PD-1+ sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics. Conclusion: Early anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations. [ABSTRACT FROM AUTHOR]

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38–0.43) and OR = 0.15 (95% CI, 0.11–0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12–0.15) and OR (for severe disease) = 0.02 (0.01–0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19–2.10), p = 0.001 and 1.25 (1.03–1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes. [ABSTRACT FROM AUTHOR]

Psoriatic disease, encompassing both psoriasis (Pso) and psoriatic arthritis (PsA), is closely intertwined with a significantly elevated risk of developing cardiovascular diseases. This connection is further compounded by a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, obesity, insulin resistance, arterial hypertension, and dysregulated lipid profiles. These comorbidities exceed the rates seen in the general population and compound the potential for increased mortality among those living with this condition. Recognizing the heightened cardiometabolic risk inherent in psoriatic disease necessitates a fundamental shift in the treatment paradigm. It is no longer sufficient to focus solely on mitigating inflammation. Instead, there is an urgent need to address and effectively manage the metabolic parameters that have a substantial impact on cardiovascular health. Within this context, apremilast emerges as a pivotal treatment option for psoriatic disease. What sets apremilast apart is its dual-action potential, addressing not only inflammation but also the critical metabolic parameters. This comprehensive treatment approach opens up new opportunities to improve the well-being of people living with psoriatic disease. This review delves into the multifaceted aspects involved in the development of cardiovascular disease and its intricate association with psoriatic disease. We then provide an in-depth exploration of the pleiotropic effects of apremilast, highlighting its potential to simultaneously mitigate metabolic complications and inflammation in individuals affected by these conditions.

Psoriatic disease (PD) and non-alcoholic fatty liver disease (NAFLD) potentially share disease pathways given the numerous inflammatory pathways involved in both diseases and a higher prevalence of NAFLD in PD patients.  Metabolic syndrome and obesity are a key link between the two diseases, but even when controlling for this, associations between both diseases are still seen. Therapeutics that impact metabolic or inflammatory pathways may be impactful in both PD and NAFLD. In this review, we describe common inflammatory pathways contributing to both PD and NAFLD and critically review the potential impact of treatments for and on both diseases.

Objectives. To assess autoimmune thyroiditis prevalence in subclinical and clinical psoriatic arthritis (PsA). Materials and methods. 45 female adult Egyptian patients with psoriatic disease were classified into 3 equal groups: PsA, subclinical PsA, and psoriasis. A full assessment was done including Health Assessment Questionnaire, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), PsA disease activity score (DAPSA), MAdrid Sonographic Enthesitis Index (MASEI), thyroid hormones (TSH, FT4, and FT3), thyroglobulin and thyroid peroxidase antibodies (Tg and TPO Abs), and thyroid ultrasound. Results. Thyroid abnormalities prevalence was: 33.3% with subclinical hypothyroidism, 80% with positive TPO Ab, and 46.7% with positive Tg Ab in PsA group, 26.7% with subclinical hypothyroidism, 60% with positive TPO Ab, and 33.3% with positive Tg Ab in subclinical PsA group and none in psoriasis group. PsA patients had higher TPO Ab levels compared to psoriasis patients with high statistical significant difference and lower FT3 levels compared to psoriasis patients with statistical significant difference. In subclinical PsA group, MASEI was positively correlated with TPO Ab with high statistical significance and with FT3 and Tg Ab with statistical significance, FT4 was negatively correlated with LEI with high statistical significance, and FT4 was correlated with PASI with statistical significance. In PsA group, TPO Ab was correlated with DAPSA with statistical significance. Conclusions. Autoimmune thyroiditis is more common in PsA than subclinical PsA patients. PsA patients are advised to be tested for TPO and Tg Abs. Musculoskeletal ultrasound is a screening tool to detect enthesitis in psoriasis patients.

Background: Psoriatic disease (PsD), including plaque psoriasis (PsO) and psoriatic arthritis (PsA), comprises a wide spectrum of manifestations and significantly impacts quality-of-life (QoL). Here, we assessed patients' understanding of PsO and PsA as a systemic disease, its impact on their physical and emotional well-being, and patients' experiences with healthcare professionals for shared treatment decision-making. Materials and Methods: The Global Psoriatic Disease and Beyond Survey was a cross-sectional, qualitative, online survey conducted on patients with moderate-to-severe PsO with/without concomitant PsA. This analysis reports findings from Indian patients. Results: Of the 261 surveyed patients, 27% with PsO reported concomitant PsA, of whom 89% reported PsA severity as moderately or highly active. Overall, 92% had heard the term "PsD," and 90% knew their condition was a systemic disease. Few were aware of PsD manifestations (palmoplantar psoriasis, 49%; nail psoriasis, 43%; axial symptoms, 40%; PsA, 34%) and comorbidities (cardiovascular disease, 33%; obesity, 30%; diabetes, 28%). Eighty-nine percent of patients indicated their skin problems had a "very-large" to "extreme-large" impact on QoL. Ninety-seven percent of patients experienced discrimination and stigmatization from others. Eighty-one percent of patients were not involved in deciding treatment goals. Few (PsO, 6%; PsA, 9%) patients were dissatisfied with current treatment; ≥50% patients reported incomplete relief of skin symptoms (PsO) and joint symptoms (PsA) as the reason for dissatisfaction. Conclusion: Lack of awareness of the manifestations and comorbidities associated with PsD and poor QoL highlights the need for patient education, shared treatment decision-making, and a multidimensional approach to PsD management in India. [ABSTRACT FROM AUTHOR]

Background: Psoriatic disease (PsD), including plaque psoriasis (PsO) and psoriatic arthritis (PsA), comprises a wide spectrum of manifestations and significantly impacts quality-of-life (QoL). Here, we assessed patients' understanding of PsO and PsA as a systemic disease, its impact on their physical and emotional well-being, and patients' experiences with healthcare professionals for shared treatment decision-making. Materials and Methods: The Global Psoriatic Disease and Beyond Survey was a cross-sectional, qualitative, online survey conducted on patients with moderate-to-severe PsO with/without concomitant PsA. This analysis reports findings from Indian patients. Results: Of the 261 surveyed patients, 27% with PsO reported concomitant PsA, of whom 89% reported PsA severity as moderately or highly active. Overall, 92% had heard the term “PsD,” and 90% knew their condition was a systemic disease. Few were aware of PsD manifestations (palmoplantar psoriasis, 49%; nail psoriasis, 43%; axial symptoms, 40%; PsA, 34%) and comorbidities (cardiovascular disease, 33%; obesity, 30%; diabetes, 28%). Eighty-nine percent of patients indicated their skin problems had a “very-large” to “extreme-large” impact on QoL. Ninety-seven percent of patients experienced discrimination and stigmatization from others. Eighty-one percent of patients were not involved in deciding treatment goals. Few (PsO, 6%; PsA, 9%) patients were dissatisfied with current treatment; ≥50% patients reported incomplete relief of skin symptoms (PsO) and joint symptoms (PsA) as the reason for dissatisfaction. Conclusion: Lack of awareness of the manifestations and comorbidities associated with PsD and poor QoL highlights the need for patient education, shared treatment decision-making, and a multidimensional approach to PsD management in India.

Background/Objectives: In recent years, a possible connection between HLA-Cw6 and a distinctive cardiometabolic (CM) profile in patients with psoriatic disease (PsD) has been proposed, although there is still little support for this. Our aim was to further investigate this possible association by studying a large population of PsD patients. Methods: For this study, three different cohorts of patients with PsD were analyzed: two with a majority of cutaneous psoriasis, pooled n: 600, and a third with only psoriatic arthritis—PsA—cases, n: 340. Potential relationships between HLA-Cw6 and the different CM risk factors (hypertension, diabetes, obesity, dyslipidemia) were analyzed using univariate and multivariate regression models, while the final net effect was assessed using fixed- or random-effects meta-analyses, as appropriate. Results: In the PsA cohort, no association was detected between HLA-Cw6 carriership and any of the CM comorbidity factors. In psoriasis cohorts, after correcting for age, sex, disease duration, and arthritis, HLA-Cw6 carriers had a reduced diabetes risk (OR 0.49, 95%CI: 0.26–0.91, p = 0.026). This latter effect was confirmed by a fixed-effects meta-analysis of the included cohorts (pooled OR: 0.50, 95%CI: 0.27–0.90). Conclusions: This work demonstrates a potential protective effect of the HLA-Cw6 allele on the risk of diabetes in PsD. Our findings together with those of others seem to confirm the existence of a novel HLA-Cw6-linked cardiometabolic endotype in this disease.

Objectives. To assess autoimmune thyroiditis prevalence in subclinical and clinical psoriatic arthritis (PsA). Materials and methods. 45 female adult Egyptian patients with psoriatic disease were classified into 3 equal groups: PsA, subclinical PsA, and psoriasis. A full assessment was done including Health Assessment Questionnaire, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), PsA disease activity score (DAPSA), MAdrid Sonographic Enthesitis Index (MASEI), thyroid hormones (TSH, FT4, and FT3), thyroglobulin and thyroid peroxidase antibodies (Tg and TPO Abs), and thyroid ultrasound. Results. Thyroid abnormalities prevalence was: 33.3% with subclinical hypothyroidism, 80% with positive TPO Ab, and 46.7% with positive Tg Ab in PsA group, 26.7% with subclinical hypothyroidism, 60% with positive TPO Ab, and 33.3% with positive Tg Ab in subclinical PsA group and none in psoriasis group. PsA patients had higher TPO Ab levels compared to psoriasis patients with high statistical significant difference and lower FT3 levels compared to psoriasis patients with statistical significant difference. In subclinical PsA group, MASEI was positively correlated with TPO Ab with high statistical significance and with FT3 and Tg Ab with statistical significance, FT4 was negatively correlated with LEI with high statistical significance, and FT4 was correlated with PASI with statistical significance. In PsA group, TPO Ab was correlated with DAPSA with statistical significance. Conclusions. Autoimmune thyroiditis is more common in PsA than subclinical PsA patients. PsA patients are advised to be tested for TPO and Tg Abs. Musculoskeletal ultrasound is a screening tool to detect enthesitis in psoriasis patients. [ABSTRACT FROM AUTHOR]

Abstract Objective To compare body composition between patients with psoriatic disease (PsD), including cutaneous psoriasis (PsO) and psoriatic arthritis (PsA), and controls, and to explore associations between disease activity and measures of function and metabolic derangement. Methods Body composition was assessed by air displacement plethysmography (ADP) and MRI-derived fat segmentation using an automated pipeline (FatSegNet). Function was assessed by Health Assessment Questionnaire (HAQ) and metabolic status by fasting lipid profile, insulin and adiponectin. Active and inactive PsO and PsA were defined by body surface area (BSA) and Psoriasis Area Severity Index (PASI) and minimal disease activity (MDA), respectively. Results Thirty patients (median disease duration 15 years; median age 52 years) and 30 BMI-matched controls were enrolled. Compared with controls, all MRI-derived body composition parameters—whole-body volume, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal adipose tissue (AAT), VAT/AAT and VAT/SAT—were higher in the PsD group, specifically, those with active disease. Body mass, body fat, whole-body volume and whole-body VAT were correlated with higher triglycerides, cholesterol:HDL (high-density lipoprotein), insulin resistance and lower adiponectin as well as higher HAQ and lower MDA. Conclusions In this pilot study, patients with PsD revealed excessive total adipose tissue and a greater volume of metabolically unfavourable ectopic fat, including VAT, compared with BMI-matched controls, which also correlated with HAQ, disease activity and overall dysmetabolism. We also provide the first evidence in patients with PsD for the clinical application of FatSegNet: a novel, automated and rapid deep learning pipeline for providing accurate MRI-based measurement of fat segmentation. Our findings suggest the need for a more integrated approach to the management of PsD, which considers both the metabolic and inflammatory burden of disease. More specifically, visceral fat is a surrogate marker of uncontrolled PsD and may be an important future target for both pharmacological and lifestyle interventions.

IntroductionPsoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory disease that negatively impacts patients’ quality of life. Patient-reported outcome measures (PROMs) are used to capture patient perspectives in disease assessment, and physicians use the Disease Activity Index for Psoriatic Arthritis (DAPSA) to evaluate disease activity in PsA. The study aimed to assess the relationship between PROMs and the DAPSA score in consecutive outpatients affected by PsA.Materials and methodsA cross-sectional study was conducted from March 2018 to October 2020 at the PsA clinic of the ARNAS Civico in Palermo (Italy), enrolling outpatients with PsA. Patients were assessed for their disease activity according to the DAPSA score, and PROMs, such as PHQ-9, HAQ, FACIT-F, and PsAID, were evaluated. Linear regression analysis evaluated the relationship between the DAPSA Score and the included PROMs.Results158 PsA consecutive peripheral subset psoriatic arthritis outpatients were recruited. The median years of illness was 10.6 (9.3–11.9), and the median DAPSA score was 19.02 (9–33.1). The regression analysis highlighted a strong relationship between the DAPSA score and the PsAID (adjR2 26%, p

Background: Patients' understanding of the systemic nature of psoriatic disease (PsD) remains insufficiently explored. Objectives: The objective of this study was to assess patients' understanding of PsD, associated comorbidities, disease burden, and relationships with healthcare professionals (HCPs). Methods: Psoriasis and Beyond was a cross-sectional, quantitative online survey conducted in patients with a self-reported, physician-given diagnosis of moderate to severe psoriasis (body surface area [BSA] >5% to <10%, affecting sensitive and/or prominent body parts or BSA ≥10%) at its worst, with/without psoriatic arthritis (PsA). Patients were recruited through online panels by the Institut de Publique Sondage d'Opinion Secteur (Ipsos SA) and patient advocacy groups. Results: Overall, 4,978 respondents with psoriasis completed the online survey from 20 countries across Australia, Asia, Europe, and the Americas; 30% of patients also reported having concomitant PsA. Overall, 69% of patients with psoriasis had heard that their disease was part of a systemic disease, and 60% had heard of the term "psoriatic disease." Despite this, recognition of common manifestations and comorbidities associated with PsD was low. Among psoriasis-only patients (n = 3,490), 38% screened positive using the Psoriasis Epidemiology Screening Tool (PEST), indicative of potential PsA. Overall, 48% of patients reported that their disease had a very large to extremely large effect on quality of life (QoL; Dermatology Life Quality Index [DLQI] score, 11–30); only 13% of patients reported no impact of the disease on QoL (DLQI, 0–1). Most patients had experienced stigma and discrimination (82%) and a negative impact on relationships (81%) in their lives. Overall, 59% of patients were not involved in deciding their treatment goals: 58% of all treated patients (n = 4,757) and 64% of treated patients with concomitant PsA (n = 1,409) were satisfied with their current treatment. Conclusions: These results highlight that patients may not fully understand the systemic nature of their disease, were frequently uninvolved in deciding treatment goals, and were often not satisfied with their current treatment. Increasing patients' participation in their care can facilitate shared decision-making between patients and HCPs, which may result in better treatment adherence and patient outcomes. Furthermore, these data indicate that policies should be implemented to protect against stigma and discrimination, which are commonly experienced by patients with psoriasis. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory condition characterized by psoriasis, synovitis, enthesitis, spondylitis, and the possible association with other extra-articular manifestations and comorbidities. It is a multifaceted and systemic disorder sustained by complex pathogenesis, combining aspects of autoinflammation and autoimmunity. Features of PsA autoinflammation include the role of biomechanical stress in the onset and/or exacerbation of the disease; the evidence of involvement of the innate immune response mediators in the skin, peripheral blood and synovial tissue; an equal gender distribution; the clinical course which may encounter periods of prolonged remission and overlapping features with autoinflammatory syndromes. Conversely, the role of autoimmunity is evoked by the association with class I major histocompatibility complex alleles, the polyarticular pattern of the disease which sometimes resembles rheumatoid arthritis and the presence of serum autoantibodies. Genetics also provide important insights into the pathogenesis of PsA, particularly related to class I HLA being associated with psoriasis and PsA. In this review, we provide a comprehensive review of the pathogenesis, genetics and clinical features of PsA that endorse the mixed nature of a disorder at the crossroads of autoinflammation and autoimmunity. [ABSTRACT FROM AUTHOR]

Approximately 25% of psoriasis patients have an inflammatory arthritis termed psoriatic arthritis (PsA). There is strong interest in identifying and validating biomarkers that can accurately and reliably predict conversion from psoriasis to PsA using novel technologies such as metabolomics. Lipids, in particular, are of key interest in psoriatic disease. We sought to develop a liquid chromatography-mass spectrometry (LC-MS) method to be used in conjunction with solid-phase microextraction (SPME) for analyzing fatty acids and similar molecules. A total of 25 chromatographic methods based on published lipid studies were tested on two LC columns. As a proof of concept, serum samples from psoriatic disease patients (n = 27 psoriasis and n = 26 PsA) were processed using SPME and run on the selected LC-MS method. The method that was best for analyzing fatty acids and fatty acid-like molecules was optimized and applied to serum samples. A total of 18 tentatively annotated features classified as fatty acids and other lipid compounds were statistically significant between psoriasis and PsA groups using both multivariate and univariate approaches. The SPME-LC-MS method developed and optimized was capable of detecting fatty acids and similar lipids that may aid in differentiating psoriasis and PsA patients. [ABSTRACT FROM AUTHOR]

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38–0.43) and OR = 0.15 (95% CI, 0.11–0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12–0.15) and OR (for severe disease) = 0.02 (0.01–0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19–2.10), p = 0.001 and 1.25 (1.03–1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes.

Background: The idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients. Methods: By multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30). Results: In 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others. Conclusion: Our findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients. [ABSTRACT FROM AUTHOR]

Background. Psoriasis (skin lesions and psoriatic arthritis PA) is a chronic inflammatory autoimmune disease that can be triggered by excessive activation of endosomal toll-like receptors (TLRs), mainly TLR9. Elevated TLR9 levels are observed in both PA and psoriasis. Therefore, studying the expression pattern of the TLR9 gene may help select therapies for patients with PA and psoriasis. Aim. To study the expression pattern of the TLR9 gene in blood mononuclear cells of PA and psoriasis patients without joint involvement for possible use in the transition to targeted therapy. Materials and methods. Mononuclear cells were isolated from the peripheral blood of 31 patients with psoriasis vulgaris without joint involvement, 45 patients with PA, and 20 healthy volunteers. TLR9 gene expression was analyzed by real-time polymerase chain reaction. Results. A comparison of expression levels in PA patients and healthy volunteers showed that the expression level of TLR9 in PA patients was 591 times higher than that in healthy volunteers. The expression level of TLR9 in psoriasis patients without joint involvement was also significantly (423-fold) higher than that in healthy subjects. Conclusion. TLR9 gene expression in mononuclear cells of psoriasis patients with severe skin lesions is similar to that in PA patients. High levels of TLR9 gene expression may be a marker of possible joint involvement in patients with psoriasis and indicate the need to reconsider the therapeutic approach to a particular patient.

BackgroundThe idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients.MethodsBy multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30).ResultsIn 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others.ConclusionOur findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients.

BackgroundSmoking is strongly associated with higher risk of psoriasis in several observational studies; however, whether this association is causal or can be explained by confounding or reverse causation is not fully understood. Randomized controlled trials are the gold standard when examining causality; however, when this method is not feasible, the Mendelian randomization design is an alternative. Herein genetic variants can be used as robust proxies for modifiable exposures and thereby avoiding confounding and reverse causation.In this study, we hypothesized that smoking is an independent and causal risk factor for psoriasis and tested this using a Mendelian randomization design.MethodsWe used data from the Copenhagen General Population Study including 105,912 individuals with full information on lifestyle factors, biochemistry, and genotype data. In total, 1,240 cases of moderate to severe psoriasis were included to investigate the association between smoking and psoriasis. To assess causality of the association, we used the genetic variant CHRNA3 rs1051730, where the T-allele is strongly associated with high lifelong cumulative smoking, as a proxy for smoking.ResultsIn observational analyses, the multivariable adjusted hazard ratio of developing moderate to severe psoriasis was 1.64 (95% confidence interval: 1.35-2.00) in ever smokers with ≤ 20 pack-years and 2.23 (1.82-2.73) in ever smokers with > 20 pack-years compared to never smokers. In genetic analyses, the odds ratio of developing moderate to severe psoriasis was 1.05 (0.95-1.16) per CHRNA3 rs10511730 T-allele in ever smokers.ConclusionSmoking was an independent risk factor for moderate to severe psoriasis in observational analyses. However, using a genetic variant as a robust proxy for smoking, we did not find this association to be causal.

Objectives: Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile. Methods: Forty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants. Results: Cytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFa production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1β, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFNγ and TNFα. Comparing each PsD subtype to HS, IL-1β and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1β and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA. Conclusion: PsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype. [ABSTRACT FROM AUTHOR]

Associations between cardiometabolic multimorbidity and response to therapy in psoriasis are unknown. Determine the associations of multimorbidity with response to biologic treatment in psoriasis patients. CorEvitas Psoriasis Registry participants who initiated biologic therapy and had 6-month follow-up were stratified by 0, 1, 2+ comorbidities (diabetes, hypertension, hyperlipidemia). Adjusted odds ratios (95% CIs) were calculated overall and separately by biologic class (TNFi, IL-17i, IL-12/23i + IL-23i), to assess the likelihood of achieving response for the 1 and 2+ groups vs. 0. Of 2,923 patients, 49.5%, 24.7% and 25.8% reported 0, 1 and 2+ comorbidities, respectively. Overall, likelihood of PASI75 was 18% (OR = 0.82; 95%CI: 0.67, 1.00) and 23% (OR = 0.77; 95%CI: 0.63, 0.96) lower in those with 1 and 2+ comorbidities, respectively, vs. 0. In those who initiated IL-17i, odds of PASI75 and PAS90 were 34% (OR = 0.66; 95%CI: 0.48-0.91) and 35% (OR = 0.65; 95%CI: 0.47-0.91) lower in the 2+ multimorbidity cohort. No significant associations were found among users of TNFi or IL-12/23i + IL-23i groups in the multimorbidity group. Patients may not be representative of all psoriasis patients. Multimorbidity in psoriasis may decrease the likelihood of achieving treatment response to biologic therapy and should be considered when discussing treatment expectations with patients. [ABSTRACT FROM AUTHOR]

Approximately 25% of psoriasis patients have an inflammatory arthritis termed psoriatic arthritis (PsA). There is strong interest in identifying and validating biomarkers that can accurately and reliably predict conversion from psoriasis to PsA using novel technologies such as metabolomics. Lipids, in particular, are of key interest in psoriatic disease. We sought to develop a liquid chromatography-mass spectrometry (LC-MS) method to be used in conjunction with solid-phase microextraction (SPME) for analyzing fatty acids and similar molecules. A total of 25 chromatographic methods based on published lipid studies were tested on two LC columns. As a proof of concept, serum samples from psoriatic disease patients (n = 27 psoriasis and n = 26 PsA) were processed using SPME and run on the selected LC-MS method. The method that was best for analyzing fatty acids and fatty acid-like molecules was optimized and applied to serum samples. A total of 18 tentatively annotated features classified as fatty acids and other lipid compounds were statistically significant between psoriasis and PsA groups using both multivariate and univariate approaches. The SPME-LC-MS method developed and optimized was capable of detecting fatty acids and similar lipids that may aid in differentiating psoriasis and PsA patients.

ObjectivesPsoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile.MethodsForty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants.ResultsCytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFα production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1β, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFN-γ and TNFα. Comparing each PsD subtype to HS, IL-1β and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1β and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA.ConclusionPsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype.

Background: Artificial intelligence (AI) has many applications in numerous medical fields, including dermatology. Although the majority of AI studies in dermatology focus on skin cancer, there is growing interest in the applicability of AI models in inflammatory diseases, such as psoriasis. Psoriatic disease is a chronic, inflammatory, immune-mediated systemic condition with multiple comorbidities and a significant impact on patients' quality of life. Advanced treatments, including biologics and small molecules, have transformed the management of psoriatic disease. Nevertheless, there are still considerable unmet needs. Globally, delays in the diagnosis of the disease and its severity are common due to poor access to health care systems. Moreover, despite the abundance of treatments, we are unable to predict which is the right medication for the right patient, especially in resource-limited settings. AI could be an additional tool to address those needs. In this way, we can improve rates of diagnosis, accurately assess severity, and predict outcomes of treatment., Objective: This study aims to provide an up-to-date literature review on the use of AI in psoriatic disease, including diagnostics and clinical management as well as addressing the limitations in applicability., Methods: We searched the databases MEDLINE, PubMed, and Embase using the keywords "AI AND psoriasis OR psoriatic arthritis OR psoriatic disease," "machine learning AND psoriasis OR psoriatic arthritis OR psoriatic disease," and "prognostic model AND psoriasis OR psoriatic arthritis OR psoriatic disease" until June 1, 2023. Reference lists of relevant papers were also cross-examined for other papers not detected in the initial search., Results: Our literature search yielded 38 relevant papers. AI has been identified as a key component in digital health technologies. Within this field, there is the potential to apply specific techniques such as machine learning and deep learning to address several aspects of managing psoriatic disease. This includes diagnosis, particularly useful for remote teledermatology via photographs taken by patients as well as monitoring and estimating severity. Similarly, AI can be used to synthesize the vast data sets already in place through patient registries which can help identify appropriate biologic treatments for future cohorts and those individuals most likely to develop complications., Conclusions: There are multiple advantageous uses for AI and digital health technologies in psoriatic disease. With wider implementation of AI, we need to be mindful of potential limitations, such as validation and standardization or generalizability of results in specific populations, such as patients with darker skin phototypes., (©Richard Barlow, Anthony Bewley, Maria Angeliki Gkini. Originally published in JMIR Dermatology (http://derma.jmir.org), 16.10.2024.)

Background/objectives: In recent years, a possible connection between HLA-Cw6 and a distinctive cardiometabolic (CM) profile in patients with psoriatic disease (PsD) has been proposed, although there is still little support for this. Our aim was to further investigate this possible association by studying a large population of PsD patients., Methods: For this study, three different cohorts of patients with PsD were analyzed: two with a majority of cutaneous psoriasis, pooled n: 600, and a third with only psoriatic arthritis-PsA-cases, n: 340. Potential relationships between HLA-Cw6 and the different CM risk factors (hypertension, diabetes, obesity, dyslipidemia) were analyzed using univariate and multivariate regression models, while the final net effect was assessed using fixed- or random-effects meta-analyses, as appropriate., Results: In the PsA cohort, no association was detected between HLA-Cw6 carriership and any of the CM comorbidity factors. In psoriasis cohorts, after correcting for age, sex, disease duration, and arthritis, HLA-Cw6 carriers had a reduced diabetes risk (OR 0.49, 95%CI: 0.26-0.91, p = 0.026). This latter effect was confirmed by a fixed-effects meta-analysis of the included cohorts (pooled OR: 0.50, 95%CI: 0.27-0.90)., Conclusions: This work demonstrates a potential protective effect of the HLA-Cw6 allele on the risk of diabetes in PsD. Our findings together with those of others seem to confirm the existence of a novel HLA-Cw6-linked cardiometabolic endotype in this disease.

Competing Interests: Conflicts of interest Dr Yap is a Principal Clinical Study Analyst at TriNetX, LLC. Dr Van Voorhees is a Consultant with Boehringer Ingelheim, BMS, and Eluciderm. Dr Enos has previously served as a consultant on an advisory board for UCB and Amgen, is an investigator for Amgen and Castle Biosciences, and has previously received research funding from the ASA/Arcutis Biotherapeutics.

Introduction: Psoriatic disease (PsD) is a chronic systemic disorder affecting numerous body areas, including skin and joints. Patients' perspectives regarding understanding their disease and dialogue with healthcare professionals (HCPs) on treatment strategies is becoming increasingly important in the holistic management of PsD. The study aim was to determine patients' understanding of the systemic nature of psoriasis and psoriatic arthritis (PsA) and the associated burden of living with these diseases. The relationship between patient and HCP was also evaluated. Methods: Psoriasis and Beyond: The Global Psoriatic Disease Survey was a cross-sectional, quantitative online survey, conducted in patients with moderate to severe plaque psoriasis with or without concomitant PsA. Here, we report interim analysis results. Results: A total of 1678 respondents from 11 countries were included. Overall, 31% of patients with psoriasis reported concomitant PsA, 80% of whom considered their PsA severity as moderately or highly active. In total, 63% of patients had heard the term "psoriatic disease". Few patients were aware of psoriasis manifestations (PsA, 29%; axial symptoms, 18%) or comorbidities (obesity, 21%; cardiovascular disease, 18%). Among patients with psoriasis and concomitant PsA, 70% reported swollen and tender joints, especially of the finger(s) and/or toe(s). Most patients (84%) experienced stigma and discrimination and reported a negative impact of their disease on work, emotions, and relationships. Overall, 42% of patients had never discussed treatment goals with their HCP. Patients who were dissatisfied with their current treatment (psoriasis, 15%; psoriasis with PsA, 14%) reported incomplete relief of skin symptoms (57%) and joint symptoms (45%) as primary reasons for dissatisfaction. Conclusions: Despite many patients having heard the term "psoriatic disease", the majority were unaware of the systemic nature and increased risk of comorbidities associated with PsD. This interim analysis highlights the need for patient education, productive patient–HCP dialogue, and shared decision-making in optimal disease management. [ABSTRACT FROM AUTHOR]

Objectives Studies have suggested phosphodiesterase 4 (PDE4) inhibition may be associated with weight loss and other cardiometabolic benefits. We evaluated the effect of the PDE4 inhibitor apremilast on body weight and composition, glucose homeostasis, lipid profiles and vascular function in psoriatic disease and whether weight change correlated with therapeutic response. Methods We conducted a prospective, open-label study (Immune Metabolic Associations in Psoriatic Arthritis) of adults receiving apremilast 30 mg as part of routine care for PsA and/or psoriasis. Cardiometabolic, anthropometric and disease activity assessments were performed at baseline (pre-apremilast) and at months 1, 3 and 6 of apremilast treatment in 60 patients. A subgroup underwent further assessment of endothelial function, body composition and adipocyte morphology. Results In patients (median age 54.5 years, 63% women, median BMI 33.2 kg/m2), apremilast was associated with a mean weight loss of 2.2 kg (95% CI 1.4, 3.0; P  < 0.001) and a mean BMI decrease of 0.8 kg/m2 (95% CI 0.5, 1.2; P  < 0.001) after 6 months of treatment. Body composition analysis demonstrated a reduction in total abdominal fat [mean decrease 0.52 L (95% CI 0.08, 0.96), P  = 0.022], principally subcutaneous adipose tissue [mean decrease 0.37 L (95% CI 0.05, 0.68), P  = 0.022]. There was no change in adipocyte diameter, haemoglobin A1c, lipid, glucagon-like peptide-1 or vascular function. Psoriatic disease activity improved with apremilast, although this was not correlated with weight change. Conclusion Following apremilast treatment, we observed weight loss, principally abdominal subcutaneous fat, and improvement in psoriatic disease activity. The latter was independent of weight change, suggesting apremilast likely acts through direct immunological mechanisms. [ABSTRACT FROM AUTHOR]

Objective: Psoriatic Disease (psoriasis - psoriatic arthritis) is an inflammatory systemic condition associated to obesity.Weight loss improves clinical severity. Mediterranean Diet (MD) has been considered a model of healthy and a very low-calorie ketogenic diet (VLCKD) is more effective for losing weight fast in obese. The study aims to determine the effectiveness of the MD and the VLCKD in the treatment of patients with inflammatory disease. Patients and Methods: Twenty patients were identified as overweight and obese from 1st to 3rd degree using Body Mass Index (BMI). MD has been proposed to overweight patients while obese patients could choose between MD and VLCKD, according to their attitudes. Then, they were divided into two study groups (MD group and KD group). Results: At baseline and after four weeks, we collected weight, BMI, waist circumference (WC) and body composition through bioimpedance analysis (BIA - Bioelectrical Impedance Analysis). At the end, both of dietary interventions were effective to improve all parameters, but we found a greater and significative reduction of BMI and WC, and more reduction of fat mass (FM) in KD group than MD group. Conclusions: Preliminary data show that KD could be proposed as a first dietary intervention to obtain a rapid weight loss and maintenance of lean mass.

Background: Psoriasis is associated with comorbid systemic metabolic disease.Objective: To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry.Methods: Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each.Results: Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group.Limitations: The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences.Conclusion: Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics. [ABSTRACT FROM AUTHOR]

Background: Psoriasis (Ps) is an inflammatory skin disease affecting over 8 million people in the USA and Canada. Approximately a quarter of patients with Ps have an inflammatory arthritis termed psoriatic arthritis (PsA). Psoriatic disease encompassing both Ps and PsA is regarded as an immune-mediated inflammatory disease, exhibiting both autoimmune and autoinflammatory features. Innate immune cell activation promotes inflammation and the cellular infiltrate in inflamed tissue is predominantly lymphocytic. Content: A narrative review of the current literature on the presence and clinical significance of autoantibodies found in psoriatic disease are presented. The frequency of several autoantibodies in Ps and PsA patients as well as their association with disease diagnosis, disease activity, and treatment response are reviewed. Summary: Despite historically described as a rheumatoid factor negative (seronegative) disease, an array of autoantibodies has been identified in patients with psoriatic disease. Many of the autoantibodies reviewed are elevated in Ps and PsA patients and are associated with disease activity, treatment response, and cardiovascular disease risk. The identification of autoantibodies in Ps and PsA patients points to an autoimmune component potentially playing a role in psoriatic disease; however, additional evidence is needed to determine the clinical utility of these autoantibodies and their contribution to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract Psoriatic disease (PsD) is a multisystem inflammatory disorder with a high prevalence of cardiovascular (CV) risk factors contributing to accelerated atherosclerosis and its sequelae. Imaging studies, notably with ultrasound, computed tomography, and positron emission tomography (PET) scanning have confirmed significant atherosclerotic change with plaque formation and vessel stenosis. Atherosclerosis is likely driven by a combination of traditional risk factors which occur more frequently in PsD and by systemic inflammation with associated pro-inflammatory cytokine production. While the mechanisms driving atherosclerosis in PsD are incompletely understood, it is now best practice to try to minimize the impact of CV risk factors by regular assessment, prevention, and treatment and also by ensuring that inflammatory musculoskeletal and cutaneous disease is adequately suppressed. Future studies need to focus on improving our understanding of the mechanisms driving atherosclerosis and, as a consequence, developing more rationale approaches to prevention and treatment.

Psoriatic disease (PsD) is a spectrum of diseases that affect both skin [cutaneous psoriasis (PsC)] and musculoskeletal features [psoriatic arthritis (PsA)]. A considerable number of patients with PsC have asymptomatic synovio-entheseal inflammations, and approximately one-third of those eventually progress to PsA with an enigmatic mechanism. Published studies have shown that early interventions to the very early-stage PsA would effectively prevent substantial bone destructions or deformities, suggesting an unmet goal for exploring early PsA biomarkers. The emergence of proteomics technologies brings a complete view of all involved proteins in PsA transitions, offers a unique chance to map all potential peptides, and allows a direct head-to-head comparison of interaction pathways in PsC and PsA. This review summarized the latest development of proteomics technologies, highlighted its application in PsA biomarker discovery, and discussed the possible clinical detectable PsA risk factors in patients with PsC.

Background: Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics.Methods: We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP—qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs.Results: We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δβ-values (p < 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-β signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-α pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients’ immune cells, characteristic of pro-inflammatory T lymphocytes.Conclusion: The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.

Psoriatic arthritis (PsA) is a chronic inflammatory disease primarily affecting peripheral and axial joints, with the possible presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease. Recently, the concept of psoriatic disease (PsD) has been proposed to define a systemic condition encompassing, in addition to joints and EAMs, some comorbidities (e.g., metabolic syndrome, type II diabetes, hypertension) that can affect the disease outcome and the achievement of remission. EAMs and comorbidities in PsA share common immunopathogenic pathways linked to the systemic inflammation of this disease; these involve a broad variety of immune cells and cytokines. Currently, various therapeutics are available targeting different cytokines and molecules implicated in the inflammatory response of this condition; however, despite an improvement in the management of PsA, comprehensive disease control is often not achievable. There is, therefore, a big gap to fill especially in terms of comorbidities and EAMs management. In this review, we summarize the clinical aspects of the main comorbidities and EAMs in PsA, and we focus on the immunopathologic features they share with the articular manifestations. Moreover, we discuss the effect of a diverse immunomodulation and the current unmet needs in PsD.

Patients with psoriasis are frequently obese and experience anxiety or suffer from depressive disorders. The immunopathogenesis of psoriasis and indeed psoriatic arthritis is largely based on the pivotal role of IL-17/IL-23 axis, to an extent that currently monoclonal antibodies selectively inhibiting IL-17 or IL-23 are routinely used for the treatment of psoriatic diseases. Emerging data, demonstrating a decisive role for IL-17 and IL-17 producing cell subsets, such as Th17 in the induction and progression of obesity and depression has led authors to suggest that psoriatic disease, obesity and anxiety/depression may indeed be interconnected manifestation of a state of immunedysregulation, the linked being IL-17 and its related cells. We discuss this hypothetical link in depth taking into account the beneficial effects anti-IL17 and anti-IL-17 receptor inhibitors in treating psoriatic disease and the on-going debate as to whether these biologics may exert a direct or indirect effect in ameliorating concomitant obesity and depressive disorders, which are frequently noted in the same patient. [ABSTRACT FROM AUTHOR]

Rosario Peluso,1 Francesco Caso,1 Marco Tasso,1 Vincenzo Sabbatino,1 Roberta Lupoli,2 Matteo Nicola Dario Di Minno,3 Francesco Ursini,4 Luisa Costa,1 Raffaele Scarpa1, On behalf of CaRRDs study group1Department of Clinical Medicine and Surgery, Rheumatology Research Unit, Federico II University, Naples, Italy; 2Department of Clinical Medicine and Surgery, Division of Internal Medicine, Federico II University, Naples, Italy; 3Department of Advanced Biomedical Sciences, Division of Cardiology, Federico II University, Naples, Italy; 4Internal Medicine Unit, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyBackground: Psoriatic arthritis (PsA) is a chronic immune-mediated disease. It is associated with an increase in cardiovascular risk factors (obesity, hypertension, diabetes, and dyslipidemia), giving a higher risk of major adverse cardiovascular events. Patients with PsA have an increased incidence of subclinical atherosclerosis and endothelial dysfunction. The aim of this study is to perform a review of the biomarkers of subclinical atherosclerosis in patients with PsA.Methods: A search was performed in the electronic databases (PubMed, Web of Science, Scopus, and Embase) up until July 2017. Studies were considered if they included data on biomarkers of subclinical atherosclerosis in PsA, and each article was then reviewed for quality and clinical relevance. After completing the literature search, all screened literature was summarized and discussed in our study group (CaRRDs study group).Results: The initial search produced 532 abstracts, which were limited to 258 potentially relevant articles by preliminary review of the titles and by excluding review articles and case reports (n=274). A further 102 articles were deemed ineligible after examining the abstracts. Full texts of the remaining 156 articles were retrieved. Most articles were excluded because they were not relevant to the biomarkers of subclinical atherosclerosis in psoriasis and/or PsA. In the end, 54 articles were deemed eligible for this review.Conclusion: Patients with PsA showed more severe atherosclerotic disease compared with patients with only psoriasis. This may have been due to the higher systemic inflammatory burden from the combination of both diseases. In patients with PsA some molecules may be considered as markers of atherosclerotic disease, and their detection may be a prognostic marker, in addition to imaging procedures, for the development of atherosclerotic disease, and could be suitable for the management of patients with PsA.Keywords: psoriatic disease, insulin resistance, lipid profile, serum uric acid, complement C3, primary and secondary hemostasis

Psoriatic arthritis is a chronic progressive systemic inflammatory disease of joints and spine, which leads to the development of erosive arthritis, bone resorbtion, multiple enthesitis and spondylitis. Severe clinical course, resistance to therapy, high prevalence of disability, increased mortality of patients determine a need for further study of the disease. Psoriatic arthritis is a multifactorial disease including immune pathogenic factors representing a complex process of interaction between cellular and humoral components of immune system. The most important way of activating epidermal cells and synovial membrane proliferation in psoriatic arthritis is an imbalance of proinflammatory and anti-inflammatory cytokines. It is noted that the features of clinical course in psoriasis are age-dependent. The study of immune response indices in different age groups allows to reveal distinct progression features of the psoriatic pathology.The purpose of this study was to compare concentrations of proinflammatory and anti-inflammatory cytokines, cellular and humoral immunity, and to conduct a comparative analysis in young and adult patients with psoriatic arthritis.The study included a group of patients with psoriatic arthritis (n = 101) who were divided by their age: group 1, from 18 to 44 years (n = 43); group 2, over 44 years (n = 58). The control groups (3 and 4) included virtually healthy people (n = 103) matched for sex and age with the patients. Populational and subpopulation profiling of blood lymphocytes was performed by flow-cytometry using monoclonal antibodies to CD3, CD4, CD8, CD16, CD19 (LLC “Sorbent”, Moscow, Russia). Phagocytic activity of peripheral blood neutrophils was assessed microscopically by uptake of latex particles. Concentrations of IgA, IgM, and IgG immunoglobulins, circulating immune complexes, cytokines (IL-4, IL-6, IL-10, TNFα) in blood serum was determined by enzyme-linked immunosorbent assay. Statistical evaluation of the results obtained was performed using applied “Statistica 6.0” software.In all the age subgroups of patients with psoriatic arthritis, we have revealedstatistically significant differences against controls, i.e., increased relative and absolute number of CD3-CD16+ lymphocytes in peripheral blood, higher concentration of CIC-C1q, with decreased concentrations of IgA, IgM, IgG in blood serum. The analysis of the main cellular and humoral indicators of immunity in psoriatic arthritis patients revealed a statistically significant differences for psoriatic arthritis in young and adulthood. E.g., the serum concentration of IL- 10 was statistically significantly lower in psoriatic arthritis at a young age in comparison with adult psoriatic arthritis. Phagocytic number and IgG concentration in serum were statistically significantly lower in adults with psoriatic arthritis adulthood than in young patients.In conclusion, The revealed changes in immunological indices in psoriatic arthritis in young and adult patients indicate to differences against healthy controls, as well as intergroup differences. Previous studies have not revealed statistically any significant differences in immunological parameters between young and adult patients with psoriatic arthritis in, thus suggesting a presence of immune disorders associated with psoriatic pathology, but not with the age of patients. However, changes of immunological reactivity are observed with increasing age of patients with psoriatic arthritis and development of severe clinical forms, and they can be considered as markers of psoriatic disease progression, such as increased concentrations of IL-10 and lower IgG amounts in blood serum, a decreased phagocytic number.

Introduction: Several new treatments have been developed for psoriatic disease, an inflammatory condition that involves skin and joints. Notwithstanding, few studies have made direct comparisons between treatments and therefore it is difficult to select the ideal treatment for an individual patient. The aim of this systematic review with network meta-analysis (NMA) was to analyze available and approved biologic therapies for each domain of psoriatic disease: skin, peripheral arthritis, axial arthritis, enthesitis, dactylitis, and nail involvement.Methods: Data from randomized clinical trials (RCTs) were included. A systematic review was performed using the MEDLINE database (July 2020) using PICO criteria. Bayesian NMA was conducted to compare the clinical efficacy of biological therapy in terms of the American College of Rheumatology criteria (ACR, 24 weeks) and Psoriasis Area and Severity Index (PASI, 10–16 weeks).Results: Fifty-four RCTs were included in the systematic review. Due to the design of the RCTs, namely, outcomes and time points, network meta-analysis was performed for skin and peripheral arthritis domains. For the skin domain, 30 studies reporting PASI100 were included. The peripheral arthritis domain was analyzed through ACR70 in 12 studies. From the therapies approved for both domains, secukinumab and ixekizumab were the ones with the highest probability of reaching the proposed outcomes. There is a lack of outcome uniformization in the dactylitis, enthesitis, and nail domains, and therefore, an objective comparison of the studies was not feasible. Nevertheless, secukinumab was the treatment with the best compromise between the number of studies in each domain and the results obtained in the different outcomes.Conclusion: Secukinumab and ixekizumab were the treatments with the highest probability of reaching both PASI100 and ACR70 outcomes. Due to the lack of a standard evaluation of outcomes of the other psoriatic disease domains, a network meta-analysis for all the domains was not possible to perform.

Psoriasis is a chronic disease, characterized by systemic inflammation with skin, joint and metabolic involvement. The most common tools to evaluate the severity of each disease is respectively the Psoriasis Area Severity Index (PASI) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). The association between psoriasis and obesity and the role of visceral fat in producing an inflammatory state have been demonstrated. The Mediterranean Diet (MD) has been recommended as a model of healthy diet on the basis of scientific evidence and considered as an adjuvant therapy for all patients affected by chronic inflammatory diseases. Our study evaluated the association between adherence to MD (assessed with the Predimed questionnaire) and psoriatic disease severity. 80 patients (40 with psoriasis and 40 with psoriatic arthritis) were evaluated for disease severity (PASI, DAPSA) and were assessed for Metabolic Syndrome according to the International Diabetes Federation (IDF) definition. To evaluate adherence to the MD, each patient was administered the Predimed questionnaire which includes 14 questions. Our study shows a correlation between low adherence to MD and a high expression of psoriasis, considering cutaneous, joint symptoms and the metabolic profile.

The chemokine receptor CCR4 has emerged as a skin-homing molecule important for the migration of T cells from the blood to the dermis. From our previous data on psoriasis patients, CCR4+ memory T cells emerged as a putative recirculating population between skin and blood. Here we focused our attention on the expression of CCR4 and skin-tropic molecules in the different stages of memory T cell differentiation. We analyzed the chemokine receptor profile in CD8+ and CD4+ CD45RA−CCR7+ (TCM) and CD45RA−CCR7− (TEM) cells. Subpopulations were further divided on the basis of CD62L expression, and the distribution among the subsets of the skin-homing molecule CLA (Cutaneous Lymphocyte Antigen) was evaluated. The characterization was performed on peripheral blood mononuclear cells isolated from 21 healthy subjects and 24 psoriasis patients. The results indicate that (i) the skin-homing CCR4 marker is mainly expressed in TCM cells, (ii) CCR4+ TCM cells also express high level of CLA and that (iii) the more differentiated phenotype TEM expresses CXCR3 and CCR5 but lower level of CCR4 and CLA. This indicates that progressive stages of memory T cell differentiation have profoundly different chemokine receptor patterns, with CD8+ TCM displaying a marked skin-tropic phenotype CLA+CCR4+. Differential skin-tropic phenotype between TCM and TEM cells was observed in both healthy subjects and psoriasis patients. However, patients showed an expanded circulating population of CD8+ TCM cells with phenotype CCR4+CXCR3+ that could play a role in the pathophysiology of psoriasis and possibly in disease recurrence.