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Background: Psoriatic arthritis (PsA) significantly contributes to increased morbidity, reduced life expectancy, and higher healthcare costs due to the burden of comorbidities. This study assessed the prevalence of comorbidities in PsA patients in India and explored the influence of age and disease duration on these comorbidities. Methods: The prospective, multicenter observational study was conducted across seven centers in India, utilizing data from the Indian Rheumatology Association. Data were collected using expert-validated proformas, with comorbidities classified according to the ICD-10 Charlson Comorbidity Index. Participants were divided into two age groups: <40 years and ≥ 40 years. Results: The study included 533 participants (median age: 50 years, range: 17–81). Comorbidities were more common among older patients (median age: 54 years, range: 41–79). About 38% had at least one comorbidity, with hypertension (17.07%) and diabetes (15.19%) being most prevalent, followed by thyroid disorders (10.13%) and hyperlipidemia (3.94%). Comorbidities were significantly more common in patients ≥ 40 years (45.04%) compared to those < 40 years (18.57%) (P < 0.001). The older group also had higher rates of hyperlipidemia (4.83% vs. 0.71%, P = 0.035) and hypertension (22.14%). Logistic regression revealed a significant association between age and the prevalence of diabetes, hypertension, and thyroid disorders (P = 0.003). Among patients over 40, 44.27% had at least one comorbidity. Conclusion: The study underscores the significant association between age and the prevalence of comorbidities in PsA patients, particularly in those over 40 years. These findings highlight the importance of targeted screening and management in older PsA patients. [ABSTRACT FROM AUTHOR]

Systematic reviews and meta-analysis evaluating the prevalence, incidence, and psychological comorbidities of psoriatic arthritis (PsA) are increasing, so it's time to perform an overview of systematic reviews. To summarize the pooled prevalence, incidence, and psychological comorbidities rates of PsA, and to explore possible continent disparities. In this overview of systematic reviews the CINAHL, EMBASE, PsycINFO, and PubMed were searched to October 25, 2023. This overview included systematic reviews with meta-analysis of people with PsA, providing the pooled prevalence or incidence rates of PsA in general, or clinical populations and/or psychological comorbidities. The Preferred Reporting Items for Overviews of Reviews (PRIOR) statement was followed. AMSTAR-2 assessed the quality of reviews. The degree of overlap was calculated using the corrected covered area (CCA). Maps were developed using the location of where primary studies were conducted using DataWrapper App. The protocol was prospectively registered with Open Science Framework registry. Pooled prevalence and incidence rates of PsA or its associated psychological comorbidities in general or specific populations. We also collected locations from the primary studies of the included meta-analyses. Only the assessment of prevalence rates of PsA in people with psoriasis showed slight overlap (CCA = 3.3%). Items 2, 3, 4, 7, 8, 10, 12, and 13 were poorly reported in AMSTAR-2. The pooled prevalence of PsA ranged from 0.13 to 0.15% in the general population, and 15.5% to 19.7% in people with psoriasis. The pooled incidence of PsA ranged from 8.26 to 9.27 cases per 100,000 inhabitants to 0.87 cases in individuals with hidradenitis suppurativa. The pooled prevalence of psychological comorbidities was 11.9–20% for depression, 19–33% anxiety, 38% alexithymia, and 72.9% in poor sleep quality. Only the pooled incidence of depression was assessed with 21.3 per 1000-person year. PsA seems to be prevalent and incident not only in people with psoriasis, but also in general population. Depression and anxiety symptoms may be present in some patients with PsA. Finally, continent disparities exist, and methodological and clinical issues were found, which could be helpful in the future agenda of the epidemiology of PsA. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques (T1 and magnetization transfer [MT] modeling) for imaging of the Achilles tendons and entheses in patients with psoriatic arthritis (PsA) compared with asymptomatic volunteers. The heels of twenty-six PsA patients (age 59 ± 15 years, 41% female) and twenty-seven asymptomatic volunteers (age 33 ± 11 years, 47% female) were scanned in the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. UTE-T1 and macromolecular proton fraction (MMF; the main outcome of MT modeling) were calculated in the tensile portions of the Achilles tendon and at the enthesis (close to the calcaneus bone). Mann-Whitney-U tests were used to examine statistically significant differences between the two cohorts. UTE-T1 in the entheses was significantly higher for the PsA group compared with the asymptomatic group (967 ± 145 vs. 872 ± 133 ms, p

Patients with psoriatic arthritis commonly have abnormalities of their entheses, which are the connections between tendons and bone. There are shortcomings with the use of conventional magnetic resonance imaging (MRI) sequences for the evaluation of entheses and tendons, whereas ultrashort echo time (UTE) sequences are superior for the detection of high signals, and can also be used for non-invasive quantitative assessments of these structures. The combination of UTE-MRI with an adiabatic-T1ρ preparation (UTE-Adiab-T1ρ) allows for reliable assessment of entheses and tendons with decreased susceptibility to detrimental magic angle effects. This study aimed to investigate the relationship between quantitative UTE-MRI measures and the biomechanical properties of Achilles tendons and entheses. In total, 28 tendon-enthesis sections were harvested from 11 fresh-frozen human cadaveric foot-ankle specimens (52 ± years old). Tendon-enthesis sections were scanned using the UTE-Adiab-T1ρ and UTE-T1 sequences on a clinical 3 T scanner. MRI-based measures and indentation tests were performed on the enthesis, transitional, and tensile tendon zones of the specimens. Hayes' elastic modulus showed significant inverse correlations (Spearman's) with UTE-Adiab-T1ρ in all zones (R= - 0.46, - 0.54, and - 0.61 in enthesis, transition, and tensile tendon zones, respectively). Oliver-Pharr's elastic modulus showed significant inverse correlations with UTE-Adiab-T1ρ in transition (R= - 0.52) and tensile tendon zone (R=- 0.60). UTE-T1 did not show significant correlations with the elastic modulus. UTE-MRI and elastic modulus were significantly lower in the tensile tendon compared with the enthesis regions This study highlights the potential of the UTE-Adiab-T1ρ technique for the non-invasive evaluation of tendons and enthuses.

Abstract The ability of 18F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18F-FDG uptake compared to unaffected areas (median difference > 0.6, p 8.5, p

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

Objective This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA. Methods A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels. Results In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (β = 0.795, CI 95%, 0.196-1.395; P =.010), -SH/(-SH+-SS) (β = -0.475, CI 95%, 0.114-0.836; P =.010) and IMA (β = 3.932, CI 95%, 0.859-7.005; P =.013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI. Conclusion In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction (ED) is defined as an impairment in the vasodilatory, anti-thrombotic, and anti-inflammatory properties of the cells that make up the lining of blood vessels. ED is considered a key step in the development of atherosclerotic cardiovascular disease. The association between ED and systemic inflammatory diseases is well established. However, the prevalence and clinical significance of ED in psoriatic arthritis (PsA) have been investigated to a lesser extent. This review aims to explore the link between ED and PsA, including ED in macro- and microcirculation, as well as risk factors for its occurrence in PsA and its relationship with atherosclerosis in PsA. Furthermore, the ED in PsA was compared with that of rheumatoid arthritis (RA). Regarding ED in the microcirculation, the coronary flow reserve was found to be significantly reduced in individuals with PsA. The relationship between PsA and macrovascular ED is more pronounced, along with more advanced atherosclerosis detected in patients with PsA. These results are consistent with those obtained in RA studies. On the other hand, arterial stiffness and signs of vascular remodeling were found more frequently in RA than in PsA, with the potential role of efficient anti-TNF treatment in patients with PsA and psoriasis explaining this finding. The impact of ED on cardiovascular diseases and the burden of this risk caused independently by PsA have not yet been precisely established, however, this group of patients requires special attention with regard to cardiovascular events. [ABSTRACT FROM AUTHOR]

The article discusses research in which dermatologists screened patients with psoriatic arthritis (PsA) using a VSCAN air handheld ultrasound device. The study assessed the accuracy of visual analogue scale diagnosis of PsA, PsA sensitivity and specificity based GErman Psoriasis ARthritis Diagnostic questionnaire scores, and entheseal tenderness.

ObjectivesTo investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression.ResultsOf 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19.ConclusionOlder age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

IntroductionEmerging evidence suggests psoriatic arthritis (PsA) with axial involvement (axPsA) and radiographic axial spondyloarthritis (r-axSpA) may possibly represent distinct disorders, with some differing clinical manifestations, genetic associations, and radiographic findings. Moreover, axPsA and r-axSpA may respond differently to therapies: guselkumab (interleukin [IL]-23p19 subunit inhibitor [i]) and ustekinumab (IL-12/23p40i) demonstrated improvements in axial symptoms in patients with PsA; however, neither risankizumab (IL-23p19i) nor ustekinumab demonstrated efficacy versus placebo in patients with r-axSpA. Current analyses aim to further understand potential molecular distinctions between axPsA and r-axSpA and examine the pharmacodynamic effects of guselkumab in patients with axPsA and those with PsA without axial involvement (non-axPsA).MethodsPost hoc analyses utilized biomarker data from blood and serum samples collected from a subset of participants in phase 3 studies of ustekinumab in r-axSpA and guselkumab in PsA (DISCOVER-1 and DISCOVER-2). Participants with axPsA were identified by investigator-verified sacroiliitis (imaging-confirmed) and axial symptoms. HLA mapping, serum cytokine analysis, and whole-blood RNA sequencing were conducted.ResultsRelative to r-axSpA, patients with axPsA had a lower prevalence of HLA-B27, HLA-C01, and HLA-C02 alleles and a higher prevalence of HLA-B13, HLA-B38, HLA-B57, HLA-C06, and HLA-C12 alleles. Compared with r-axSpA, patients with axPsA had elevated baseline levels of serum IL-17A and IL-17F cytokines, enrichment of IL-17 and IL-10 pathway-associated genes, and neutrophil gene markers. Across axPsA and non-axPsA cohorts, reductions in cytokine levels and normalization of pathway-associated gene expression with guselkumab treatment were comparable.ConclusionThe differences in HLA genetic associations, serum cytokines, and enrichment scores support the concept that axPsA and r-axSpA may be distinct disorders. The comparable pharmacodynamic effects of guselkumab on cytokine levels and pathway-associated genes observed in patients with axPsA and non-axPsA are consistent with demonstrated clinical improvements across PsA cohorts. These findings contribute to the understanding of potential genetic and molecular distinctions between axPsA and r-axSpA.Trial registrationClinicalTrials.gov identifiers, NCT03162796, NCT0315828, NCT02437162, and NCT02438787.

This study aimed to investigate the duration of diagnostic delay in patients with psoriatic arthritis (PsA) and identify potential contributing factors using a comprehensive, population-based approach. Data were obtained from the Turkish League Against Rheumatism (TLAR)-Network, involving patients who met the CASPAR criteria. Diagnostic delay was defined as time interval from symptom onset to PsA diagnosis, categorized as ≤ 2 years and > 2 years. Temporal trends were assessed by grouping patients based on the year of diagnosis. Various factors including demographics, clinical characteristics, disease activity, quality of life, physical function, disability, fatigue, and well-being were examined. Logistic regression models were used to identify factors associated with diagnostic delay. Among 1,134 PsA patients, mean diagnostic delay was 35.1 months (median: 12). Approximately 39.15% were diagnosed within 3 months, and 67.02% were diagnosed within 24 months. Patients experiencing longer delays had higher scores in Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient's global assessment (PtGA) and physician's global assessment (PhGA). Diagnostic delay has decreased over time, with median delay falling from 60 to 24 months throughout pre-2010 and 2015–2019 terms. Several factors were identified as significant contributors to delayed diagnosis, including lower levels of education (OR = 2.63), arthritis symptoms preceding skin manifestations (OR = 1.72), low back pain at first visit (OR = 1.60), symptom onset age (OR = 0.96), and psoriasis subtype (OR = 0.25). Timely diagnosis of PsA is crucial for effective management and improved outcomes. Despite recent improvements, about one-third of PsA patients still experience delays exceeding 2 years. By identifying influential factors such as education level, arthritis symptoms preceding skin manifestations, initial visit symptoms, age of symptom onset, and psoriasis subtype, healthcare practitioners may create specific techniques to help in early detection and intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND/AIM: Craniocervical junction (CCJ) can be involved in inflammatory arthritis. We aimed to define types of CCJ involvement in rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) and compare them with patients without inflammatory arthritides. MATERIALS AND METHODS: In this retrospective analysis, cervical CT or MRIs of patients with RA, SpA, or PsA, taken for any reason between 2010 and 2020, according to ICD-10 codes, were scanned. Demographic data of the patients were recorded. CCJ involvements (atlantoaxial, vertical, or subaxial subluxation, odontoid process involvement) were reevaluated by an experienced radiologist. The control group consisted of consecutive patients without inflammatory arthritis. RESULTS: Exactly 459 patients (204 RA, 200 SpA, and 55 PsA) and 78 patients in the control group were included in the study. CCJ involvement was detected in 101 (49.5%) RA, 53 (26.5%) SpA, 10 (18.2%) PsA, and 4 patients (5.1%) in the control group (p < 0.001). The odontoid process was one of the main targets, especially in RA patients (69 (33.8%)), which was significantly higher than in the SpA, PsA, and control groups. Although vertical subluxation (VS) was numerically higher in the RA and SpA groups compared to the control group, VS-related brainstem compression was relatively uncommon: 6 (2.9%) in RA, 1 (0.5%) in AS, and none in the PsA and control groups. CONCLUSION: CCJ involvement can often be detected in patients with inflammatory arthritis, especially in RA and SpA patients. The odontoid process is the main target of inflammation.

OBJECTIVE: This study was undertaken to identify the mechanistic role of γδ T cells in the pathogenesis of experimental psoriatic arthritis (PsA). METHODS: In this study, we performed interleukin-23 (IL-23) gene transfer in wild-type (WT) and T cell receptor δ-deficient (TCRδ-/- ) mice and conducted tissue phenotyping in the joint, skin, and nails to characterize the inflammatory infiltrate. We further performed detailed flow cytometry, immunofluorescence staining, RNA sequencing, T cell repertoire analysis, and in vitro T cell polarization assays to identify regulatory mechanisms of γδ T cells. RESULTS: We demonstrated that γδ T cells support systemic granulopoiesis, which is critical for murine PsA-like pathology. Briefly, γδ T cell ablation inhibited the expression of neutrophil chemokines CXCL1 and CXCL2 and neutrophil CD11b+Ly6G+ accumulation in the aforementioned PsA-related tissues. Although significantly reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A was detected systemically in TCRδ-/- mice, no GM-CSF+/IL-17A+ γδ T cells were detected locally in the inflamed skin or bone marrow in WT mice. Our data showed that nonresident γδ T cells regulate the expansion of an CD11b+Ly6G+ neutrophil population and their recruitment to joint and skin tissues, where they develop hallmark pathologic features of human PsA. CONCLUSION: Our findings do not support the notion that tissue-resident γδ T cells initiate the disease but demonstrate a novel role of γδ T cells in neutrophil regulation that can be exploited therapeutically in PsA patients.

Objective. To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. Methods. Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. Results. The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. Conclusion. SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with psoriatic arthritis (PsA) experience reduced physical function and impaired quality of life. Better patient-reported functional outcomes are found when lower disease activity is achieved. Objectives To evaluate the variation of physical function by HAQ-DI over time in PsA patients treated with standard therapy in a real-life setting: to verify predictors of achieving a minimum clinically important difference (MCID) in function by HAQ-DI (ΔHAQ-DI ≤ − 0.35) and to measure the impact of achieving REM/LDA on long-term function by HAQ-DI. Methods This is a longitudinal analysis of a real-life retrospective cohort. Data from PsA patients with at least 4 years of follow-up in the PsA clinic from 2011 to 2019 were extracted from electronic medical records. The variations of physical function by HAQ-DI and disease activity by DAPSA over time were calculated. A multivariate hierarchical regression model was applied to verify predictors of MCID in HAQ-DI. A comparison of HAQ-DI variation between patients with DAPSA REM, LDA, moderate and high disease activity was made using the generalized estimating equation model (GEE), adjusted by Bonferroni test. The Spearman correlation method was applied to verify the correlation of ΔDAPSA and ΔHAQ-DI over time. Statistical analysis was performed in SPSS program version 21.0. Results Seventy-three patients were included in the analysis. Physical function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (p

Abstract Background Psoriasis is a protean disease associated with several comorbidities that may have increased levels of adiponectin such as resistin. This may affect the patients atherosclerotic risk. Objective To study resistin levels in a sample of Brazilian patients with psoriasis and its association with clinical profile, comorbidities, and carotid Intima-Media Thickness (cIMT). Methods This is a cross-sectional study of 119 individuals: 34 healthy controls and 85 patients with psoriasis, 42 of which with skin involvement only and 43 with psoriatic arthritis. Clinical and epidemiological data, measurement of PASI (Psoriasis Area Severity Index) and DAPSA (Disease Activity in Psoriatic Arthritis), lipid profile, cIMT by ultrasound were collected from medical records. Resistin serum levels were measured by ELISA. Results Patients with psoriasis had higher resistin levels (p = 0.009) and worse cIMT (p = 0.0002) than controls. In the psoriasis sample, no associations of resistin levels with epidemiological, clinical findings, and activity indexes were found. Resistin serum levels were associated with the presence of diabetes (p = 0.008) and metabolic syndrome (p = 0.01) and correlated with total cholesterol (r = 0.26) and triglycerides (r = 0.33) but not with cIMT. Study limitations This work is limited by its transversal design and by the limited number of patients included. Conclusion Resistin serum levels are elevated in psoriasis patients. In this sample, clinical, epidemiological, and activity indexes were not linked to resistin serum levels, but atherosclerotic risk factors were.

Purpose of reviewThis article discusses publications assessing the prevalence, efficacy, and safety of opioid analgesics in patients with rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis, and systemic sclerosis.Recent findingsRecent studies show long-term opioid use is common in patients with inflammatory rheumatic disease. We did not find any studies demonstrating improved function or pain control with long-term opioid use in people with rheumatic diseases. Some data shows potential adverse effects including increased risk for fractures and opioid poisoning hospitalizations. There is evidence demonstrating an association of opioid use with mental health disorders, fibromyalgia, obesity, and disability, although causative links have not been established. Only minimal reductions in opioid use were observed after initiation of biologic disease modifying antirheumatic drugs (DMARDs). Studies have shown delayed DMARD initiation and reduced DMARD use in patients on opioids, raising concerns that these analgesics may delay care or initially mask symptoms of active disease.SummaryAvailable literature highlights high levels of opioid use in people with rheumatic disease, without scientific evidence to support efficacy for chronic pain control and increasing evidence of adverse events. These findings strongly suggest that opioids do not have a routine role in the chronic management of inflammatory rheumatic diseases.

Background: Psoriatic arthritis (PsA) is a systemic auto-immune condition characterized by diverse and distinctive inflammation, affecting both musculoskeletal and extra-articular systems. This study aims to investigate the role of regulatory T-cells (Tregs), specifically the CD4+CD25+/high CD127-/low subset, in PsA pathogenesis, and their potential as biomarkers and therapeutic targets. Materials and Methods: In a case-control study involving 40 PsA patients and 25 healthy individuals, CD4+ CD25+/high CD127-/low Tregs were analyzed in peripheral blood mononuclear cells (PBMCs) using flow cytometry. Disease activity was assessed using the Disease Activity in Psoriatic Arthritis (DAPSA) score. Results: We observed a significant positive correlation between Treg levels and the DAPSA score (P = 0.02) in non-treated PsA patients. Additionally, patient age showed a significant positive correlation with erythrocyte sedimentation rate in the same group (P = 0.04), emphasizing the potential influence of Tregs on disease activity and age-related effects on inflammatory markers in PsA. Conclusion: While not revealing significant differences in Treg populations, our research underscores the importance of considering specific Treg subsets in PsA. These subsets may respond differently to disease micro-environments and treatments, affecting disease progression. This study contributes to the broader comprehension of immune dysregulation in auto-immune diseases and suggests that further investigation into Treg subsets’ function and count is warranted. Such insights may lead to more tailored therapeutic approaches for PsA patients.

Early diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts. Cell type-specific gene and protein expression differences between PSA, PSO, and healthy groups, along with 200 previously published genetic risk factors for PSA, were further used to perform machine learning classification, with the best models achieving AUROC ≥ 0.87 when either classifying subjects among the three groups or specifically distinguishing PSA from PSO. Our findings thus expand the repertoire of gene, protein, and cellular biomarkers relevant to PSA and demonstrate the utility of machine learning-based diagnostics for this disease.

BackgroundOxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers.MethodsConsecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1.ResultsTwenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without.ConclusionsThe AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients.

Given the impact of the coronavirus disease 2019 (COVID-19) on patients with psoriatic disease (PsD), a session was devoted at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting to discussing the current understanding of the risk of severe COVID-19 in patients with PsD. The effects of PsD and its treatment on prevention and treatment of COVID-19 with vaccinations, antiviral drugs, and monoclonal antibodies were discussed. The session concluded with a presentation on the perspectives of patient research partners about their experiences with COVID-19. [ABSTRACT FROM AUTHOR]

One of the highlights of the 2022 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting was the trainee symposium. Dermatology and rheumatology trainees presented their research related to psoriasis and psoriatic arthritis. This report briefly reviews 5 oral presentations and 15 posters that were selected for this annual meeting. Topics include basic/translational, clinical, and outcomes research reflecting the spectrum of GRAPPA's effort and influence nationally and internationally in the area of psoriatic diseases. [ABSTRACT FROM AUTHOR]

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting, the Collaborative Research Network (CRN) met to present updates on several projects. These included the GRAPPA-Industry biomarker projects, Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Axial Involvement in Psoriatic Arthritis Cohort (AXIS) study, and the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES). The meeting concluded with a discussion on pathways to further academia-industry collaboration. [ABSTRACT FROM AUTHOR]

Although psoriasis and psoriatic arthritis (PsA) have been classically considered to be diseases of the skin and joints, respectively, emerging evidence suggests that a combination of innate and environmental factors creates widespread immune dysfunction, affecting multiple organ systems. A greater understanding of the pathogenesis of psoriasis and the systemic effects of psoriatic inflammation has allowed for the development of new, more effective treatments. The second portion of this two-part review series examines the comorbidities associated with psoriasis and PsA as well as the most recent advances in targeted systemic therapies for these conditions.

ObjectiveAnkylosing spondylitis (AS) and psoriatic arthritis (PsA) often affect the hip and/or knee. If effective, treatments might reduce risk of total hip or total knee arthroplasty (THA/TKA). We evaluated risk of THA/TKA related to use of medical therapies in AS/PsA.MethodsWe conducted a nested case-control study using 1994-2018 data from the OptumLabs Data Warehouse, which includes deidentified medical and pharmacy claims, laboratory results, and enrollment records for commercial and Medicare Advantage enrollees. Among those with AS/PsA, THA/TKA cases were matched up to 4 controls by sex, age, AS/PsA diagnosis, diagnosis year, insurance type, obesity, and prior THA/TKA. We assessed AS/PsA treatment 6 months prior to THA/TKA, including disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibitors (TNFi), alone or in combination, stratified by nonsteroidal antiinflammatory drug (NSAID) use. We evaluated the relation of treatment to risk of THA/TKA using conditional logistical regression with adjustment for confounders.ResultsAmong 16,748 adults with AS, there were 444 THA/TKA cases and 1613 matched controls. Among 34,512 adults with PsA, there were 1003 cases and 3793 controls. Adjusted ORs for treatment category and THA/TKA ranged from 0.60 to 1.92; however, none were statistically significant. Results were similarly null in several sensitivity analyses.ConclusionOdds of THA/TKA were not reduced with any combinations of NSAIDs, DMARDs, or TNFi among persons with AS or PsA. Given current utilization patterns in this population of US adults with AS and PsA, these medical therapies did not appear to be associated with less end-stage peripheral joint damage.

We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.

This study aims to investigate the relationship between disease duration and psychological burden in PsA and to identify the risk factors associated with psychological distress. Patients with PsA who met CASPAR classification criteria enrolled by Turkish League Against Rheumatism (TLAR)-Network. Patients were categorized into three groups based on disease duration: early stage (< 5 years), middle stage (≥ 5, < 10 years), and late stage (≥ 10 years). All patients underwent clinical and laboratory assessment using standardized protocol and case report forms. The associations between psychological variables and clinical parameters were assessed by a multivariate analysis. Of the 1113 patients with PsA (63.9% female), 564 (%50.7) had high risk for depression and 263 (%23.6) for anxiety. The risk of psychological burden was similar across all PsA groups, and patients with a higher risk of depression and anxiety also experienced greater disease activity, poorer quality of life, and physical disability. Multivariate logistic regression revealed that female gender (OR = 1.52), PsAQoL (OR = 1.13), HAQ (OR = 1.99), FiRST score (OR = 1.14), unemployment/retired (OR = 1.48) and PASI head score (OR = 1.41) were factors that influenced the risk of depression, whereas the current or past enthesitis (OR = 1.45), PsAQoL (OR = 1.19), and FiRST score (OR = 1.26) were factors that influenced the risk of anxiety. PsA patients can experience a comparable level of psychological burden throughout the course of their disease. Several socio-demographic and disease-related factors may contribute to mental disorders in PsA. In the present era of personalized treatment for PsA, evaluating psychiatric distress can guide tailored interventions that improve overall well-being and reduce disease burden. [ABSTRACT FROM AUTHOR]

Patients with chronic inflammatory arthritis have a higher cardiovascular (CV) risk than the general population. Traditional CV risk factors are clearly implicated, while the impact of metabolic syndrome (MetS) is less defined. The aim of this study was to compare MetS prevalence and impact on the CV risk in psoriatic arthritis (PsA) versus rheumatoid arthritis (RA). A retrospective analysis of real-world data of PsA and RA patients referred to a rheumatology clinic was conducted. The following data were extracted and compared: demographic data; clinical data; presence of traditional CV risk factors and MetS. Univariate and multivariate models were used to compare the impact of MetS and its components in patients with PsA versus RA. Overall, 170 patients were included (PsA: 78; RA; 92). The two groups differed significantly in mean age, disease duration, and presence of MetS, while other variables were comparable. Univariate and multivariate analysis identified distinct predictors of MetS in PsA (hypertension) and RA (dyslipidemia). The history of CV events was similar in the two groups. Predictors of CV events were MetS and most of its components in PsA, while dyslipidemia was the strongest predictor in RA. These associations were stronger in PsA than in RA. In conclusion, the impact of MetS and its components is different in PsA and RA. The association of these risk factors with CV events is stronger in PsA than in RA. This suggests the implication of different mechanisms, which may require distinct strategies for the prevention of CV events in PsA and RA. [ABSTRACT FROM AUTHOR]

Psoriasis is a common multifactorial autoimmune disease of the skin, and in a large percentage of patients, immune responses involve nail and joint pathology, which develop psoriatic arthritis (PsA). Historically, T helper 1 (Th1)-derived-IFN-γ was abundantly detected in psoriatic skin and its correlation with development and severity of PsO, led to an early classification of psoriasis as a Th1-mediated disease. Investigations of the cellular and molecular mechanisms of PsO pathogenesis in recent years, together with impressive results of biologics against interleukin 17A (IL-17) have shifted focus on IL-17A. However, the contributions of IFN-γ in IL-17 induced pathology and its involvement in the development of PsA have been largely overshadowed. This review summarizes the current knowledge on IFN-γ and provides new insights on the contribution of IFN-γ to PsO and PsA disease pathogenesis and development.

Over the past few years, there have been several scientific advances related to the discovery of interleukin 23 (IL-23) and IL-17 which led to the development of new treatment options and overall improved clinical care of Psoriatic Arthritis (PsA) patients. Many of these efforts and milestones, alongside new developments, are captured in this Clinical Immunology special edition. We also take the opportunity to highlight the overall scientific progress in PsA research and also highlight some areas of concern that continue to represent barriers in the PsA arena that need to be addressed. These areas are 1) basic & translational research, 2) clinical diagnosis 3) treatment and 4) medical education and awareness.

OBJECTIVE: To add to data on adverse birth outcomes accounting for disease activity in women with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: Data were analyzed from women enrolled in the Organization of Teratology Information Specialists Autoimmune Disease Project from 2004 to 2018. Disease activity was measured according to the Health Assessment Questionnaire (HAQ) or Routine Assessment of Patient Index Data 3 (RAPID3) scores. Poisson regression was used to estimate adjusted risk ratios (ARRs) with 95% confidence intervals (95% CIs) for selected adverse pregnancy outcomes. RESULTS: Compared to healthy controls (n = 717), women with PsA (n = 117) were at increased risk for moderate preterm delivery (32-36 weeks gestation) (ARR 1.81, 95% CI 1.01-3.26), oligohydramnios (ARR 3.79, 95% CI 1.34-10.74), and cesarean delivery (ARR 1.63, 95% CI 1.26-2.12). Women with AS (n = 129) had an increased risk of delivering infants requiring intensive care (ARR 1.67, 95% CI 1.05-2.67). A high HAQ score at 32 weeks was associated with preterm delivery in women with PsA (ARR 3.82, 95% CI 1.51-9.67). In women with AS, a high RAPID3 score was associated with cesarean delivery (ARR 5.82, 95% 1.06-31.78), and second trimester glucocorticoid use was associated with preterm delivery (ARR 4.41, 95% CI 1.57-12.41). CONCLUSION: Women with PsA and AS have increased risk for selected adverse pregnancy outcomes. Active disease and use of glucocorticoids may increase the risk for some adverse pregnancy outcomes in women with these conditions.

ObjectivesCOVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease.MethodsCase series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed.ResultsA total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed.ConclusionsWe found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

ObjectiveTo add to data on adverse birth outcomes accounting for disease activity in women with psoriatic arthritis (PsA) and ankylosing spondylitis (AS).MethodsData were analyzed from women enrolled in the Organization of Teratology Information Specialists Autoimmune Disease Project from 2004 to 2018. Disease activity was measured according to the Health Assessment Questionnaire (HAQ) or Routine Assessment of Patient Index Data 3 (RAPID3) scores. Poisson regression was used to estimate adjusted risk ratios (ARRs) with 95% confidence intervals (95% CIs) for selected adverse pregnancy outcomes.ResultsCompared to healthy controls (n = 717), women with PsA (n = 117) were at increased risk for moderate preterm delivery (32-36 weeks' gestation) (ARR 1.81, 95% CI 1.01-3.26), oligohydramnios (ARR 3.79, 95% CI 1.34-10.74), and cesarean delivery (ARR 1.63, 95% CI 1.26-2.12). Women with AS (n = 129) had an increased risk of delivering infants requiring intensive care (ARR 1.67, 95% CI 1.05-2.67). A high HAQ score at 32 weeks was associated with preterm delivery in women with PsA (ARR 3.82, 95% CI 1.51-9.67). In women with AS, a high RAPID3 score was associated with cesarean delivery (ARR 5.82, 95% 1.06-31.78), and second trimester glucocorticoid use was associated with preterm delivery (ARR 4.41, 95% CI 1.57-12.41).ConclusionWomen with PsA and AS have increased risk for selected adverse pregnancy outcomes. Active disease and use of glucocorticoids may increase the risk for some adverse pregnancy outcomes in women with these conditions.

ObjectiveTo characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients.MethodsFecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n = 5) were analyzed for expression of IL-23/Th17-related cytokines, IL-25/IL-17E-producing cells, and type 2 innate lymphoid cells (ILC2s).ResultsThere were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (P < 0.05), compared to pre-IL-17i treatment levels.ConclusionIn a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20ZF7 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20ZF7 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner.

BACKGROUND:Psoriasis is the most common chronic inflammatory condition involving the T helper cell system. Population studies have demonstrated that patients with psoriasis and/or psoriatic arthritis have an increased risk of developing vascular risk factors, including diabetes, hypertension, and obesity, and increased risk of adverse vascular events, including myocardial infarction and stroke. Population studies have generally investigated the individual contributions of psoriasis and psoriatic arthritis to development of vascular risk factors; fewer studies have investigated the additive contribution of comorbid inflammatory disorders. We present a case of a woman with psoriasis, psoriatic arthritis, and comorbid vascular risk factors. CASE PRESENTATION:A 49 year-old Caucasian woman with a history of severe psoriasis and psoriatic arthritis since adolescence presented with bilateral lower extremity weakness. She was found to have acute bilateral watershed infarcts and multifocal subacute infarcts. Her evaluation revealed vascular risk factors and elevated non-specific systemic inflammatory markers; serum and cerebral spinal fluid did not reveal underlying infection, hypercoagulable state, or vasculitis. Over the course of days, she exhibited precipitous clinical deterioration related to multiple large vessel occlusions, including the bilateral anterior cerebral arteries and the left middle cerebral artery. Autopsy revealed acute thrombi and diffuse, severe atherosclerosis. CONCLUSION:Patients with early onset inflammatory disease activity or comorbid inflammatory disorders may have an even higher risk of developing metabolic syndrome and adverse vascular events compared to patients with late-onset disease activity or with a single inflammatory condition. The described case illustrates the complex relationship between inflammatory disorders and vascular risk factors. The degree of systemic inflammation, as measured by severity of disease activity, has been shown to have a dose-response relationship with comorbid vascular risk factors and vascular events. Dysregulation of the Th1 and Th17 system has been implicated in the development of atherosclerosis and may explain the severe atherosclerosis seen in such chronic inflammatory conditions. Further research will help refine screening and management guidelines to account for comorbid inflammatory disorders and related disease severity.

Purpose: Apremilast is a phosphodiesterase-4 inhibitor FDA approved for psoriatic arthritis and moderate to severe plaque psoriasis. In recent years, multiple studies have suggested other potential uses for apremilast in dermatology. A summary of these various studies will be a valuable aid to dermatologists considering apremilast for an alternative indication.Materials and methods: The PubMed/MEDLINE and ClinicalTrials.gov databases were queried with the term 'apremilast,' with results manually screened to identify published data on off-label uses of apremilast. The article was structured by the quality of evidence available.Results: Apremilast use in dermatology beyond plaque psoriasis and psoriatic arthritis is frequently described in the literature, with a mixture of positive and negative results. Randomized controlled data is available for Behçet's disease, hidradenitis suppurativa, nail/scalp/palmoplantar psoriasis, alopecia areata, and atopic dermatitis.Conclusion: The relatively safe adverse effect profile of apremilast and its broad immunomodulatory characteristics may make it a promising option in the future for patients with difficult to treat diseases in dermatology, refractory to first line therapies, but further studies will be necessary to clarify its role.

There are limited data regarding cycling between interleukin-17 (IL-17) inhibitors in psoriatic arthritis (PsA). We aimed to report the efficacy of an IL-17 inhibitor (ixekizumab—IXE) after inadequate response (IR) of another one (secukinumab—SEC) in patients with PsA. Case series of PsA patients who received IXE after SEC-IR in four rheumatology centers between 1/9/2021 and 1/9/2022 were included. Peripheral arthritis was assessed with disease activity in psoriatic arthritis score (DAPSA) and skin involvement with body surface area (BSA). Axial disease was defined as having both imaging and clinical features and its activity was measured with the ankylosing spondylitis disease activity score (ASDAS). Twenty-four patients (54.2% female, mean [SD] age: 51.6 [14.1]) who were SEC-IR and received IXE either immediately (n = 11) or after ≥ 1 interposed biologic disease modifying anti-rheumatic drug (bDMARD) (n = 13) were included. Patients were followed on IXE for a mean [SD] period of 9.6 [4.9] months. Among patients with peripheral arthritis (n = 24), the mean [SD] DAPSA decreased from 22.8 [8.6] to 13.6 [7.8] during follow-up (p = 0.0001) with 62.5% of patients showing improvement in the DAPSA disease activity categories. For patients with axial involvement (n = 16), a clinically meaningful improvement (Δ ≥ 1.1 in ASDAS) was noted in 50% (8/16), while dactylitis and enthesitis resolution was observed in 60% (3/5) and 83% (5/6) of patients, respectively. Regarding psoriasis, the mean [SD] BSA of involved skin decreased from 8.7 [8.7] to 2.4 [3.3] (p = 0.001). In this case series, treatment with IXE after inadequate response to another IL-17 inhibitor (SEC) was efficacious in a real-world setting in patients with PsA, including axial disease. [ABSTRACT FROM AUTHOR]

Young-GRAPPA (Y-GRAPPA) was introduced at the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting. Here we present the 1-year progress of Y-GRAPPA and future plans of this enthusiastic group of young clinicians and early career researchers interested in psoriasis and psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Psoriasis (PsO) is a chronic inflammatory skin disease with both local and systemic components. PsO-associated arthritis, known as psoriatic arthritis (PsA), develops in approximately 13%-25% of PsO patients. Various factors associated with both PsO and PsA indicate that these conditions are part of a single disease. Identification of novel targets for the development of drugs to treat both PsO and PsA is desirable to provide more patient-friendly treatment regimens. Such targets will likely represent 'common checkpoints' of inflammation, for example key components or transduction cascades of the signalling pathways involved. Emerging evidence supports involvement of the non-canonical Wnt signalling pathways in the development of both PsO and PsA, especially the Wnt5a-activated signalling cascades. These, together with interlinked factors, are crucial in the interactions among keratinocytes, immune cells and inflammatory factors in PsO, as well as among chondrocytes, osteoblasts and osteoclasts that trigger both subchondral bone remodelling and cartilage catabolism in PsA. This review focuses on the pathological role of Wnt5a signalling and its interaction with other interlinked pathways in both PsO and PsA, and also on the main challenges for future research, particularly with respect to molecules targeting Wnt signalling pathways for the treatment of PsO and PsA.

OBJECTIVE:Determine the contribution of joint and skin improvements to health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). METHODS:SPIRIT-P1 and SPIRIT-P2 are phase 3 trials investigating ixekizumab, an interleukin-17A antagonist, in the treatment of patients with active PsA. Patients were randomised to ixekizumab or placebo. Outcomes included the Disease Activity Index for Psoriatic Arthritis (DAPSA), the Psoriasis Area and Severity Index (PASI), the European Quality of Life-Five Dimensions (EQ-5D) Visual Analogue Score (VAS), the 36-Item Short-Form Health Survey (SF-36) and the Work Productivity and Activity Impairment (WPAI) Questionnaire. The contribution of joint and skin improvements to HRQoL was modelled using a smoothing spline method and depicted with response surface graphics. RESULTS:In this integrated analysis, 402 patients with PsA had baseline psoriasis of ≥3% of body surface area. We applied response surface modelling to this patient data set to investigate the relationship between DAPSA, PASI and HRQoL improvements at week 24. The greatest improvement in EQ-5D VAS was associated with the largest per cent improvements in both DAPSA and PASI together, rather than DAPSA or PASI alone. Similar observations were made in domains of SF-36 and WPAI. CONCLUSION:Optimal improvements in patients' HRQoL were dependent on successful treatment of both joint and skin symptoms.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis of unknown etiology, and currently the cellular and molecular interactions that dictate its pathogenesis remain elusive. A role of the interleukin-23 (IL-23)/IL-23R (IL-23 receptor) interaction in the development of psoriasis and PsA is well established. As IL-23 regulates the differentiation and activation of innate and adaptive immunity, it pertains to a very complex pathophysiology involving a plethora of effectors and transducers. In this review, we will discuss recent advances on the cellular and molecular pathophysiological mechanisms that regulate the initiation and progression of PsA as well as new therapeutic approaches for IL-23/IL-23R targeted therapeutics.

IntroductionTheoretical risks of biologic agents remain under study.ObjectiveThe aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials.MethodsPatients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]).ResultsAmong 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications.ConclusionsUstekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications.Trial registrationsClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355.