Psoriatic arthritis: from pathogenesis to therapy.

Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis.

Exercise and manual physiotherapy arthritis research trial (EMPART): a multicentre randomised controlled trial.

Background: Osteoarthritis (OA) of the hip is a major cause of functional disability and reduced quality of life. Management options aim to reduce pain and improve or maintain physical functioning. Current evidence indicates that therapeutic exercise has a beneficial but short-term effect on pain and disability, with poor long-term benefit.

Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis.

We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis clinic. At the time of recruitment, all had clinical evidence of synovitis.

Biological biomarkers in psoriatic disease. A review.

Biomarkers are important in clinical practice because they allow quantitative assessment of diagnosis, disease processes, and treatment response. However, because development of biomarkers lags significantly behind that of drug development, absence of new and appropriate markers may slow the development of patient-tailored targeted therapies. At the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of the biomarker committee discussed the possible use of biomarkers in psoriasis and psoriatic arthritis and reviewed the results of several studies of biomarkers in the pathogenesis, diagnosis, and treatment of both the inflammatory and dermatologic aspects of psoriatic disease.

Clues to the pathogenesis of psoriasis and psoriatic arthritis from imaging: a literature review.

This article summarizes a presentation on imaging of skin and joints in patients with psoriasis and psoriatic arthritis (PsA) from the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Plain radiography provides valuable insights into the pathogenesis of PsA but is limited because only calcified tissue can be imaged. Newer techniques such as magnetic resonance imaging (MRI) and ultrasound (US) provide additional clues to the pathogenesis of this peripheral, axial, and dermatologic disease.

Measurement of periarticular bone mineral density in the hands of patients with early inflammatory arthritis using dual energy x-ray absorptiometry.

Hand bone densitometry is more sensitive than standard radiology in the measurement of disease-related bone damage in early arthritis. Most studies employing dual energy x-ray absorptiometry (DXA) have evaluated the whole hand. The aim of this study was to evaluate a method that quantified bone density in regions of interest that were confined to the juxta-articular areas of metacarpo-phalangeal (MCP) and proximal interphalangeal (PIP) joints.

Immunohistochemistry of the inflamed synovium.

The development in the techniques for obtaining synovial tissue biopsy, especially through arthroscopy, have resulted in greater access to high-quality synovial tissue. The use of immunohistochemistry in arthritis research has greatly furthered our understanding of the varied immunological and biochemical pathways involved in inflammatory arthropathopies such as rheumatoid and psoriatic arthritis. Immunohistochemistry provides a strikingly visual narrative of the essential elements involved in inflammatory arthritis, from the infiltrating inflammatory cells (e.

Early changes in serum type II collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy.

Objective: To investigate whether short-term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis.

Methods: Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (DeltaCOL) was calculated.

Increased expression of the orphan nuclear receptor NURR1 in psoriasis and modulation following TNF-alpha inhibition.

The orphan nuclear receptor NURR1 belongs to the NR4A subfamily of transcription factors which are emerging as important mediators of cytokine and growth factor signaling. The transcriptional function of these ligand-independent and constitutively active receptors is controlled at the level of expression and nuclear localization. This study examines the expression of NURR1 in psoriasis and biological effects on this receptor following inhibition of tumor necrosis factor-alpha (TNF-alpha) signaling.

Consensus on a core set of domains for psoriatic arthritis.

A psoriatic arthritis (PsA) module was convened at OMERACT 8 in order to achieve consensus on the core domains that should be included in randomized controlled trials and longitudinal observational cohorts of subjects with PsA. Following a plenary session at which current status of measures used to assess PsA were reviewed, and discussion at breakout groups, the group achieved consensus on 6 core domains: peripheral joint activity, skin activity, pain, patient global assessment, physical function, and health-related quality of life. In addition the following domains were considered important but not mandatory: spinal disease, dactylitis, enthesitis, fatigue, nail disease, radiography, physician global assessment, and acute-phase reactants.

Outcome measures in psoriatic arthritis.

Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor, has emerged as a more common and severe disease than previously appreciated. The disease is multifaceted. Thus the assessment of PsA requires attention to peripheral joint involvement, axial disease, dactylitis, and enthesitis, as well as the skin manifestations.

Filaggrin null alleles are not associated with psoriasis.

Psoriasis is a common skin disease with an etiology consistent with a multifactorial trait. Several psoriasis susceptibility loci are known, a number of which are also implicated in a predisposition to atopic dermatitis (AD), including the epidermal differentiation complex on chromosome 1q21. It has recently been shown in several replicate studies that prevalent null alleles for the filaggrin gene (FLG) on 1q21 are an important genetic factor in AD.

Synovial macrophages as a biomarker of response to therapeutic intervention in rheumatoid arthritis: standardization and consistency across centers.

Successive studies from one academic center (Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands) have consistently suggested that synovial tissue expression of sublining macrophages may be a biomarker of clinical response to therapeutic intervention in rheumatoid arthritis (RA) clinical trials. A proof-of-concept, randomized clinical trial was completed at a second academic center (St. Vincent's University Hospital, Dublin, Ireland), and the relationship between the change in disease activity and the change in sublining macrophages in distinct treatment cohorts was determined.

A role for type 1alpha corticotropin-releasing hormone receptors in mediating local changes in chronically inflamed tissue.

Peripheral corticotropin-releasing hormone (CRH) is an important regulator of localized inflammatory responses. The aim of this study is to define the pathological signaling pathways in which peripheral CRH receptor-mediated responses reside. We report that PECAM-1-expressing synovial membrane endothelial cells are the principal source of CRH receptor subtype 1alpha in chronically inflamed synovial tissue (ST).

Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures.

Objective: To investigate the role of oncostatin M (OSM) in cell adhesion, angiogenesis, and matrix degradation in rheumatoid arthritis (RA) synovial tissue and normal human cartilage.

Methods: Human dermal microvascular endothelial cell (HDMEC) and RA synovial fibroblast (RASF) proliferation and intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression were assessed by a bromodeoxyuridine proliferation assay and flow cytometry. HDMEC tubule formation and migration were assessed by Matrigel culture and migration assay.

Spondyloarthropathy: disease at the crossroads of immunity.

Up until recently, the prevailing paradigm relating to spondyloarthropathy (SpA) pathogenesis was that they were human leukocyte antigen (HLA)-associated, T-cell-driven autoimmune diseases. This view is now being questioned. Careful studies of well-characterised cohorts of patients with SpA, including detailed analysis of involved tissue, together with clinical trials of targeted treatments, in particular anti-tumour necrosis factor (TNF) therapies, have contributed enormously to both interest in and understanding of disease pathogenesis.

Psoriatic arthritis: one or more diseases?

Psoriatic arthritis (PsA) is a common, debilitating auto-immune disease with diverse clinical features. In this paper, published evidence is examined, which addresses the issues that (a) PsA exists; and (b) PsA can or cannot be viewed as a distinct rheumatic disease from other spondyloarthritides. Evidence derived from epidemiological, clinical, genetic and immunohistological studies is included.

Identification of synovial biomarkers of response to experimental treatment in early-phase clinical trials in spondylarthritis.

Objective: To identify biomarkers for effective treatment in early-phase clinical trials of spondylarthritis (SpA), by analyzing which synovial features can be reliably identified in patients with SpA.

Methods: Synovial biopsies were performed at weeks 0 and 12 in 20 SpA patients treated with infliximab, 20 treated with etanercept, and 12 who were not treated. Primary clinical outcome measures were patient and physician global assessment of disease activity.

Resolution of endothelial activation and down-regulation of Tie2 receptor in psoriatic skin after infliximab therapy.

Background: Psoriasis is a common dermatosis characterized by erythematous skin plaques and associated arthritis. Microvessels of the papillary dermis in psoriatic lesions are elongated, tortuous, and dilated, which contributes significantly to the proinflammatory response. Angiopoietin (Ang) 1 and 2 and their receptor, Tie2, are a family of growth factors recognized in inflammatory lesions to be critical for new blood vessel growth and maintenance, with recent studies suggesting tumor necrosis factor (TNF)-alpha-induced angiogenesis is in part mediated by the Tie2 receptor.

Acute-phase serum amyloid A stimulation of angiogenesis, leukocyte recruitment, and matrix degradation in rheumatoid arthritis through an NF-kappaB-dependent signal transduction pathway.

Objective: To examine the role of the acute-phase protein serum amyloid A (A-SAA) in regulating cell adhesion molecule expression, leukocyte recruitment, and angiogenesis in rheumatoid arthritis (RA).

Methods: Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and matrix metalloproteinase 1 (MMP-1) expression was examined in RA fibroblast-like synoviocytes (FLS) and human microvascular endothelial cells (HMVECs) using flow cytometry and enzyme-linked immunosorbent assay techniques. Peripheral blood mononuclear cell (PBMC) adhesion to FLS/HMVECs was determined by flow cytometry.

Synovial tissue analysis in clinical trials.

Synovial tissue analysis has considerable potential for future randomized controlled trials (RCT). The synovial membrane is the target tissue in treatment strategies of rheumatoid arthritis and other arthropathies. Effective modulation of synovitis is critical when attempting to control symptoms and signs, to prevent joint damage, and to maintain function.

Modulation of orphan nuclear receptor NURR1 expression by methotrexate in human inflammatory joint disease involves adenosine A2A receptor-mediated responses.

Modulation by proinflammatory mediators indicate that NURR1 induction represents a point of convergence of distinct signaling pathways, suggesting an important common role for this transcription factor in mediating multiple inflammatory signals. The present study identifies NURR1 as a molecular target of methotrexate (MTX) action in human inflammatory joint disease and examines the mechanism through which MTX modulates NURR1 expression. MTX significantly suppresses expression of NURR1 in vivo in patients with active psoriatic arthritis (n = 10; p < 0.

Psoriatic arthritis synovial histopathology: commentary on the article by Kruithof and colleagues.

The clinical features in psoriatic arthritis straddle the divide between rheumatoid arthritis on the one hand and spondyloarthropathy on the other. The paper by Kruithof and colleagues compares synovial immunohistologic features and clearly identifies psoriatic arthritis as being a member of the spondyloarthropathy family.