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High prevalence and distinct patterns of metabolic syndrome in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis: a population-based study.

INTRODUCTION: Metabolic syndrome (MetS) in inflammatory arthritis (IA) directly impacts its management and associated morbidity and mortality. MetS is a well-recognised comorbidity in PsA, but the epidemiology across IA is unclear. This study aimed to characterise the prevalence of MetS across rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) compared to controls. METHODS: We performed a cross-sectional analysis of half a million individuals from the UK Biobank, aged 40 to 69 years, who were collected between 2006 and 2010. Participants with RA, PsA, and axSpA were identified using ICD-10 codes and/or read codes. MetS was defined according to adapted National Cholesterol Education Program Adult Treatment Panel III criteria. Statistical analysis included ANOVA and chi-squared test for between-group difference and logistic regression for odds of MetS, adjusted for age, sex, CRP and smoking status. RESULTS: The prevalence of MetS was highest in RA (43.4%), followed by PsA (42.3%), axSpA (37.1%) and controls (31.8%). Hypertension was prevalent across all IAs (~&#x2009;80%), as was hypertriglyceridaemia. Elevated waist circumference and dysglycaemia were more prevalent in RA and PsA compared to axSpA. The adjusted odds of comorbid MetS were elevated in RA (OR 1.15; 95% CI 1.07, 1.24; p&#x2009;<&#x2009;0.001) and PsA (OR 1.31; 95% CI 1.13, 1.52; p&#x2009;<&#x2009;0.001) compared to controls, but decreased in axSpA (OR 0.82; 95% CI 0.70, 0.96; p&#x2009;=&#x2009;0.012). CONCLUSION: RA and PsA, but not axSpA, are associated with an increased odds of MetS. Holistic management strategies that address both IA and MetS are essential for improving mortality and morbidity.

Humans

Immunological studies on synovial joint membranes in psoriatic arthritis.

Psoriatic arthritis (PA) is included in the seronegative arthritis group, though it is now generally considered to represent a clinical entity. In PA, in contrast to psoriasis vulgaris and to other types of rheumatoid arthritis, only a few immunological studies have been reported. In the present report synovial joint membranes from patients with PA and control groups have been studied for the presence of (a) vascular changes, (b) fibrin, (c) immunoglobulins and complement factor C3.

Arthritis

The clinical spectrum of psoriatic arthritis.

Epidemiologic, clinical, radiologic and serologic evidence suggests that psoriatic arthritis is a specific entity and not the coincidental occurrence of 2 common diseases, psoriasis and rheumatoid arthritis. Psoriatic arthritis may be defined as psoriasis associated with inflammatory arthritis (peripheral arthritis or spondylitis or both) and usually a negative serologic test for rheumatoid factor. Clinical characteristics of the disease include: almost equal distribution between males and females; peripheral arthritis involving only a few small joints in asymmetical fashion; involvement of distal interphalangeal joints; sausage digits; arthritis mutilans; ankylosing spondylitis; goutlike onset; and higher frequency of nail involvement than occurs in uncomplicated psoriasis. The rash may present with arthritis, or, equally, may precede or succeed joint involvement. With regard to pain and disability, the prognosis in psoriatic arthritis is better than in rheumatoid arthritis.

Arthritis

Immunofluorescence studies for immunoglobulins and complement C3 in synovial joint membranes in psoriatic arthritis.

Synovial tissues from fifteen patients with psoriatic arthritis were investigated with direct immunofluorescence staining for immunoglobulins (IgG, IgA, and IgM) and from eigth patients for complement component C3. As control groups, there were synovial tissues from seven patients with seropositive rheumatoid arthritis and five patients with meniscal tears. In psoriatic arthritis, immunoglobulins were found in plasma cells in 93% of the cases, always with the presence of IgG (93%) but also with IgA (47%) and IgM (7%). C3 could not be demonstrated. In seropositive rheumatoid arthritis IgG was demonstrated in all patients (100%), often together with IgA (43%) and IgM (57%). C3 was found in all of these patients. In patients with meniscal tears neither immunoglobulins nor C3 could be found. The present findings indicate immunological activity in synovial membranes in psoriatic arthritis. The low amount of IgM and the lack of C3 suggest a difference compared to seropositive rheumatoid arthritis.

Arthritis

Uncovering metabolite-immune interactions in the pathogenesis of psoriatic arthritis: A 2-sample Mendelian randomization study.

PsA is a chronic inflammatory joint condition associated with psoriasis, and its underlying mechanisms are not fully elucidated. Serum metabolites, as direct reflections of metabolic status, may influence disease progression by regulating immune cell function; however, the causal relationships and specific pathways require further investigation. The present investigation utilized a 2-sample bidirectional MR methodology, leveraging extensive pooled GWAS data to thoroughly evaluate the causal relationships between 1440 serum metabolites and PsA. Additionally, mediation MR analysis was performed to explore the possible mediating effects of 731 immune cell characteristics. In the primary analysis, inverse-variance weighted was employed, and this was further supported by various sensitivity analyses to confirm the reliability of the findings. The genetic method to infer causality analysis revealed significant positive causal associations between 10 serum metabolites and PsA risk, with quinolinate levels demonstrating the most significant correlation (OR&#x2005;=&#x2005;1.56, 95% CI: 1.26-1.93); while 4 metabolites (e.g., citrate levels, OR&#x2005;=&#x2005;0.74, 95% CI: 0.61-0.89) exhibited protective effects. Regarding immune cells, 6 cellular features (e.g., CD20 on B cells) were positively correlated with disease risk, whereas 5 features (primarily HLA-DR expression on monocyte subsets) showed negative correlations. Mediation analysis identified 3 significant pathways,the percentage of the effect explained by the mediator: N6,N6,N6-trimethyllysine levels mediated via B cells (CD20 on IgD+ CD38br), with a proportion of 33.2%; 1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6) levels mediated through monocytes (HLA-DR on CD14- CD16-) with a 32.0% proportion; the unknown metabolite X-24736 also mediated 42.1% of the protective effect via the same monocyte phenotype. This study revealed that elevated amino acid-related metabolites and glycerophospholipids significantly increase PsA risk through immune cell effects. These are closely associated with PsA pathogenesis and may serve as potential biomarkers. The novel findings underscore metabolic-immune interactions as targets for biomarkers and therapies in PsA, advancing personalized medicine.

Humans

The nail dystrophy of psoriatic arthritis.

Nail abnormalities occur frequently in patients with psoriatic arthritis. This study of the finger nails of 46 patients with psoriatic arthritis, 100 nonpsoriatic rheumatism patients, and 100 nonpsoriatic general medical patients was designed to characterise these abnormalities with particular reference to the severity of nail pitting. The results of the study suggest: (1) Onycholysis alone in the absence of previous injury to the affected nail is in favour of a psoriatic origin for the nail dystrophy. (2) Two or all of onycholysis, horizontal ridging, and nail pitting in the same patient are in favour of a psoriatic origin for the nail dystrophy. (3) The presence or absence of nail pitting alone is a poor discriminator between psoriatic and other causes for nail dystrophy. (4) More than 20 finger nails pits per person is suggestive of a psoriatic cause for the dystrophy. (5) More than 60 pits per person is unlikely to be found in the absence of psoriasis.

Arthritis

Photochemotherapy and psoriatic arthritis. A prospective study.

We have studied the temporal relation between psoriasis and psoriatic arthritis in 27 patients receiving photochemotherapy for treatment of psoriasis. Patients were classified as either spondylitic or nonspondylitic. For spondylitic patients, psoriasis was difficult to control, arthritis did not improve, and skin and joint activity appeared to vary independently. In contrast, 67% of nonspondylitic patients receiving photochemotherapy treatment remained clear of psoriasis, with 49% mean improvement in articular index. There was an inverse relation between initial percentage of psoriasis and improvement in peripheral arthritis. These results suggest that aggressive management of psoriasis helps control synovitis in at least a subgroup of patients with psoriatic arthritis.

Arthritis

Differentiation between psoriatic arthritis and rheumatoid arthritis: a biochemical and statistical analysis of fingernail amino acids.

The differentiation between psoriatic arthritis and rheumatoid arthritis can be clinically difficult if there is no manifest psoriasis of skin or nail. In order to clarify this diagnostic problem, the amino acid patterns in seventy-five psoriatic and non-psoriatic nails have been studied. Using gas--liquid chromatographic techniques and discriminant analysis, a high degree of differentiation (96%) has been established between the normal looking nails of patients with psoriatic arthritis and those with rheumatoid arthritis. This biochemical/statistical approach to the fingernail enhances diagnosis in difficult clinical problems, particularly where there are no overt manifestations of psoriasis.

Amino Acids

Predominance of cells with T-markers in the lymphocytic infiltrates of synovial tissue in psoriatic arthritis.

Synovial tissue from 8 patients with psoriatic arthritis (PSA) were investigated by direct immunofluorescence technique with FITC-conjugated anti-F(ab')2 antiserum, and with a specific rabbit anti-human T-lymphocyte antiserum by indirect immunofluorescence method with FITC-conjugated goat-anti-rabbit Ig antiserum as the second layer. The majority of the lymphocytes in the tissue displayed membrane fluorescence with the anti-T antiserum. Staining with the conjugated anti-F(ab')2 antiserum revealed both intra- and extracellular immunoglobulins. These results indicate that the majority of the lymphocytes in the synovial tissue of PSA are T-lymphocytes, and that a minor number of the cells belong to the B-cell line.

Arthritis

[Psoriatic arthritis: analysis of 69 cases and review of the literature].

In a retrospective study 69 cases of psoriatic arthritis evaluated at the Centre hospitalier de l'université Laval (CHUL) between 1968 and 1977 were studied. Certain clinical and laboratory features (age, sex, nail involvement, date of onset of the cutaneous psoriasis, date of onset of the arthritis, and the presence or absence of rheumatoid factor and the HLA-B27 antigen) and the radiologic data were compared with findings previously described in the literature. With three exceptions the findings compared well: at CHUL (a) the frequency of the HLA-B27 antigen in patients with axial psoriatic arthritis was very low, (b) patients with synchronous psoriasis and arthritis were not more severely affected, and (c) certain radiologic signs that seem to be rare and have probably been overemphasized in the literature were not found.

Adult

Psoriatic arthritis and HLA antigens.

HLA groups including the characteristics of 25 antigens were determined in 108 patients suffering from psoriatic arthritis. These included 18 patients with central forms (pelvospondylitis), and 90 patients with peripheral forms (polyarthritis with or without sacroiliitis). Analysis of the results leads to the following conclusions: central psoriatic arthrisis is strongly associated with B27 and BW38, less closely with B13 and slightly with BW17. Peripheral psoriatic arthritis has the same relationship with the HLA system as has psoriasis without arthropathy.

Arthritis

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA na&#xef;ve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration &#x2265; 3 mg/L, and &#x2265; 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans

Pathogenesis of psoriasis and psoriatic arthritis: Insights from animal models and single-cell and spatial transcriptomic analyses of skin, synovium and entheses.

Psoriasis (PsO) and psoriatic arthritis (PsA) are immune-mediated diseases characterized by chronic systemic inflammation, including inflammation of the skin and joints. Recent advances in animal models, single-cell transcriptomics, spatial transcriptomics, and proteomics have greatly enhanced our understanding of disease pathogenesis. Mouse models exhibit key features of skin and joint inflammation, facilitating analysis of molecular pathways, and identification of therapeutic targets. Single-cell and spatial transcriptomic analyses have revealed cell-type-specific contributions to inflammation, highlighting interactions between keratinocytes, T cells, fibroblasts, and dendritic cells that drive psoriatic pathology. In psoriatic synovium, type 17 tissue-resident memory T cells, monocytes, and fibroblasts contribute to local inflammation and joint damage, whereas the roles of B cells and plasma cells are less clear. Proteomic and metabolomic profiling in patients with PsA has identified circulating protein signatures and metabolites associated with disease progression, sex-specific differences, and response to therapy. The integration of these multiomic approaches provides a detailed map of immune-stromal-epithelial crosstalk across skin, synovium, and entheses, uncovering mechanisms that were previously inaccessible. These insights have implications for predicting disease progression, identifying novel therapeutic targets, and optimizing treatment strategies. Collectively, advances in animal models and multiomic profiling are reshaping our understanding of PsO and PsA, providing a framework for future research, disease monitoring, and therapeutic development.

Animals

An Immunosenescent CD8+ T Cell Subset in Patients with Axial Spondyloarthritis and Psoriatic Arthritis Links Spontaneous Motility to Telomere Shortening and Dysfunction.

OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA). METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from patients with r-axSpA (n = 128), PsA (n = 60), and rheumatoid arthritis (RA) (n = 74) and healthy donors (HDs) (n = 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA sequencing analysis, whereas telomere length and dysfunction were measured by reverse transcriptase-polymerase chain reaction and immunofluorescence-fluorescence in situ hybridization, respectively. RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared with HDs and patients with RA. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (tumor necrosis factor), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response activation, telomere shortening, and dysfunction. CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in patients with SpA that represents a possible player in disease pathogenesis.

Humans

Psoriatic arthritis and anti-nuclear factor.

Positive tests for anti-nuclear factor were found in 7% of 101 patients with psoriatic arthritis. In only one case was this at a significantly high titre. The overall prevalence is that expected in the community, though there was a high prevalence in those with Sjögren's syndrome. This is a further differentiating feature from rheumatoid arthritis.

Adult

Deposition of fibrinogen (FR-antigen) in skin diseases. III. Synovial joint membranes in psoriatic arthritis.

Synovial joint membranes obtained by synovectomy in open bloodless fields were examined for FR-antigen (fibrinogen/fibrin-related antigen) in 15 patients with psoriatic arthritis (ps.a.) and in a control group of 5 patients with meniscal tears. All frozen and paraffin sections from ps.a. demonstrated FR-antigen at the synovial lining. In the tissue it was located at the surface and in cytoplasm of the superficial synovial cells. In the control group, FR-antigen was present in all frozen samples as a thin layer at the synovial lining surface, but absent in the paraffin sections. The presence of FR-antigen may contribute to the further development of the Inflammatory changes of the arthritis.

Antigens

Antinuclear antibodies in ankylosing spondylitis, psoriatic arthritis, and psoriasis.

Granulocyte-specific antinuclear antibodies (GS-ANA) were detected in the sera of 5 of 88 patients with ankylosing spondylitis (AS) and in 7 of 52 cases of psoriatic arthritis (PsA), but were not found in 91 patients with malignant or non-malignant chest disease nor in 25 cases of psoriasis. Organ non-specific ANA were present in serum from 6 cases of AS and 1 of PsA. None of the sera gave significant levels for soluble immune complexes as detected by a C1q-binding assay. The presence of antinuclear antibodies was not associated with clinical features or drug therapy in either AS or PsA.

Antibodies, Antinuclear