Rheumatoid Arthritis: Conaghan P

Emery P, Conaghan P, Quinn M. · No affiliation provided · J Rheumatol. · Pubmed #11409108 links to  free full text

This publication has no abstract.

Bird P, Conaghan P, Ejbjerg B, McQueen F, Lassere M, Peterfy C, Edmonds J, Shnier R, O'Connor P, Haavardsholm E, Emery P, Genant H, Østergaard M. · Department of Rheumatology, St. George Hospital, University of NSW, Sydney, Australia. · Ann Rheum Dis. · Pubmed #15647422 links to  free full text

Abstract: Based on a previously developed rheumatoid arthritis MRI scoring system (OMERACT 2002 RAMRIS), the development team agreed which joints, MRI features, MRI sequences, and image planes would best illustrate the scoring system in an atlas. After collecting representative examples for all grades for each abnormality (synovitis, bone oedema, and bone erosion), the team met for a three day period to review the images and choose by consensus the most illustrative set for each feature, site, and grade. A predefined subset of images (for example, for erosion--all coronal slices through the bone) was extracted. These images were then re-read by the group at a different time point to confirm the scores originally assigned. Finally, all selected images were photographed and formatted by one centre and distributed to all readers for final approval.

McQueen F, Lassere M, Edmonds J, Conaghan P, Peterfy C, Bird P, O'Connor P, Ejbjerg B, Klarlund M, Stewart N, Emery P, Shnier R, Genant H, Østergaard M. · Department of Rheumatology, Auckland Hospital, New Zealand. · J Rheumatol. · Pubmed #12784423 No free full text.

Abstract: Magnetic resonance image (MRI) scanning is a new method for imaging and quantifying joint inflammation and damage in rheumatoid arthritis (RA). Over the past 4 years, the OMERACT MR Imaging Group has been developing and testing the RA-MRI scoring system (RAMRIS) for use in RA. The OMERACT filter demands that an ideal outcome measure satisfy the elements of truth, discrimination, and feasibility. The RAMRIS as it currently stands incorporates measures of joint inflammation and damage including bone erosion, edema, and synovitis. Tendonitis has not been scored because of feasibility issues; joint space narrowing, reflecting cartilage damage, has also been excluded as reliability was low at the small joints of the hands. Anatomical coverage of the score is currently restricted to the wrists and hands but can provide a basis for a more comprehensive score. The MR measurement of synovitis correlates closely with histological evidence and work continues on validating MR erosions with reference to radiographic techniques. The RAMRIS has demonstrated good reliability for bone erosion and synovitis at the wrists and metacarpophalangeal joints subject to reader training, with slightly lower levels of reader agreement for bone edema. Reliability was less satisfactory in discriminating between 2 time points, and further work is required if the score is to be used to monitor change. Feasibility also needs to be considered for the practical application of the score, including the time taken for scanning and scoring, as well as cost and safety issues. The OMERACT RAMRIS provides a framework for scoring inflammation and damage in RA upon which further modifications can be built. It has been endorsed by the MRI working group and OMERACT 6 participants as useful for inclusion as an outcome measure in clinical trials.

Østergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, Shnier R, O'Connor P, Klarlund M, Emery P, Genant H, Lassere M, Edmonds J. · Danish Research Center of Magnetic Resonance and Department of Rheumatology at the Copenhagen University Hospital at Hvidovre, Denmark. · J Rheumatol. · Pubmed #12784422 No free full text.

Abstract: This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists, which was developed by an international MRI-OMERACT group. MRI definitions of important RA joint pathologies, and a "core set" of basic MRI sequences for use in RA are also suggested.

Peterfy C, Edmonds J, Lassere M, Conaghan P, Østergaard M, McQueen F, Genant H, Klarlund M, Ejbjerg B, Stewart N, Bird P, Shnier R, O'Connor P, Emery P. · Synarc Inc., San Francisco, California 94105, USA. · J Rheumatol. · Pubmed #12784418 No free full text.

Abstract: The rationale for an OMERACT Module on the use of magnetic resonance imaging (MRI) in the assessment of rheumatoid arthritis (RA) is outlined. This article also details the way in which the RA MRI Working Group developed and undertook a series of structured exercises to evaluate the reliability and sensitivity to change of the RA-MRI score (RAMRIS).

Conaghan P, Edmonds J, Emery P, Genant H, Gibbon W, Klarlund M, Lassere M, McGonagle D, McQueen F, O'Connor P, Peterfy C, Shnier R, Stewart N, Ostergaard M. · Rheumatology Research Unit, University of Leeds, UK. · J Rheumatol. · Pubmed #11361206 No free full text.

Abstract: Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

Quinn MA, Green MJ, Conaghan P, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, 36 Clarendon Road, Leeds, LS2 9JT, UK. · Best Pract Res Clin Rheumatol. · Pubmed #11358414 No free full text.

Abstract: There are difficulties in making an accurate diagnosis of rheumatoid arthritis in its early stages, a principal problem being the fact that its most defining feature is chronicity, which, by definition, takes time to identify. There is substantial evidence that patients with rheumatoid arthritis should be treated early, and the majority are now commenced on therapy when first diagnosed. A logical implication of the early therapy approach is that treatment before rheumatoid arthritis is fully developed may have even greater benefits. This requires patients who are likely to have a persistent, more severe disease to be identified and treated effectively in the very earliest stages. This requires a system of the early specialist referral of suitable patients and the use of effective predictors of patient outcome. This text discusses the early arthritis clinic approach and the current evidence base available for use in constructing management guidelines for such patients.

Ostergaard M, Klarlund M, Lassere M, Conaghan P, Peterfy C, McQueen F, O'Connor P, Shnier R, Stewart N, McGonagle D, Emery P, Genant H, Edmonds J. · Department of Rheumatology and Danish Research Centre of Magnetic Resonance, Hvidovre Hospital, University of Copenhagen. · J Rheumatol. · Pubmed #11361204 No free full text.

Abstract: Magnetic resonance imaging (MRI) allows direct visualization of inflammation and destruction in rheumatoid arthritis (RA) joints. However, MRI scoring methods have not yet been standardized or appropriately validated. Our aim was to examine interreader agreement for a simple system of scoring RA changes on MRI among 5 centers that had not undertaken intergroup calibration. MRI of RA wrist and metacarpophalangeal (MCP) joints were scored by experienced readers in 5 centers in different countries. In substudy 1, 5 sets of 2nd-5th MCP joints from UK [Technique A: 1.5 T, coronal and axial T1 and T2 spin-echo, -/+ fat saturation (FS), -/+ iv gadolinium (Gd)] were scored for synovitis (score 0-3) and bone lesions (0-3). In substudy 2, we evaluated 19 sets of 2nd-5th MCP joints [10 sets from UK (Technique A) and 9 sets from the US (Technique B: 1.5 T; coronal T1 spin-echo and T2* gradient-echo + FS, no Gd)] and 19 wrist joints [9 from the US (Technique B) and 10 from Denmark (Technique C: 1.0 T; coronal and axial T1 spin-echo, no FS, -/+ Gd)]. Synovitis (0-3), bone lesions (0-3), and joint space narrowing (JSN, 0-3) were scored in each MCP joint and in 3 different regions of the wrist. Bone erosions and lesions in each bone were scored 0-5. Substudy 1 served to test and redesign the score sheets. In substudy 2, the scores of synovitis and bone lesions by the 5 groups were the same or differed by only one grade in 73% and 85% of joints, respectively. On MRI that included 2 imaging planes and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa values were in the low to moderate range, generally lowest for JSN (< 0.20), better for synovitis and bone erosions, and best for bone lesions, being generally highest for MRI with 2 planes pre- and post-Gd and in MCPjoints compared with wrists. These preliminary results suggest that the basic interpretation of MRI changes in RA wrist and MCP joints is relatively consistent among readers from different countries and medical backgrounds, but that further training, calibration, and standardization of imaging protocols and grading schemes will be necessary to achieve acceptable intergroup reproducibility in assessing synovitis and bone destruction in RA multicenter studies.

Burgoyne CH, Field SL, Brown AK, Hensor EM, English A, Bingham SL, Verburg R, Fearon U, Lawson CA, Hamlin PJ, Straszynski L, Veale D, Conaghan P, Hull MA, van Laar JM, Tennant A, Emery P, Isaacs JD, Ponchel F. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #17644540 No free full text.

Abstract: OBJECTIVES: An abnormal CD4+ T cell subset related to inflammation exposure (inflammation-related cells, IRC) has been identified in rheumatoid arthritis (RA). Patients with inflammatory and non-inflammatory diseases were used to examine the relationship between inflammation and this T cell subset in vivo. METHODS: Blood was collected from healthy controls and patients with RA (active disease or in clinical remission), Crohn's disease and osteoarthritis. IRC and chemokine receptors were quantified by flow cytometry. Thymic activity and apoptotic factors were measured by real-time polymerase chain reaction. Circulating cytokines were measured by enzyme-linked immunosorbent assay. CXCR4 and SDF1 in synovial biopsies were measured using immunohistochemistry. RESULTS: IRC were identified in patients with RA (p<0.0001) and Crohn's disease (p = 0.005), but not in those with osteoarthritis. In RA in remission, IRC persisted (p<0.001). In remission, hyperproliferation of IRC was lost, chemokine receptor expression was significantly lowered (p<0.007), Bax expression dropped significantly (p<0.001) and was inversely correlated with IRC (rho = -0.755, p = 0.03). High IRC frequency in remission was associated with relapse within 18 months (OR = 6.4, p<0.001) and a regression model predicted 72% of relapse. CONCLUSIONS: These results suggest a model in which, despite the lack of systemic inflammation, IRC persist in remission, indicating that IRC are an acquired feature of RA. They have, however, lost their hyper-responsiveness, acquired a potential for survival, and no longer express chemokine receptors. IRC persistence in remission confirms their important role in chronic inflammation as circulating precursors of pathogenic cells. This was further demonstrated by much higher incidence of relapse in patients with high IRC frequency in remission.

McQueen F, Østergaard M, Peterfy C, Lassere M, Ejbjerg B, Bird P, O'Connor P, Genant H, Shnier R, Emery P, Edmonds J, Conaghan P. · Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand. · Ann Rheum Dis. · Pubmed #15647421 links to  free full text

Abstract: This paper outlines the most important pitfalls which are likely to be encountered in the assessment of magnetic resonance images of the wrist and metacarpophalangeal joints in patients with rheumatoid arthritis. Imaging artefacts and how these can be recognised using various sequences and views are discussed. Normal structures such as interosseous ligaments and nutrient foramina may appear prominent on certain images and need to be identified correctly. Pathological change in the rheumatoid hand involves many tissues and when substantial damage has occurred, it may be difficult to identify individual structures correctly. Bone erosion, bone oedema, synovitis, and tenosynovitis frequently occur together and in close proximity to each other, potentially leading to false positive scoring of any of these. Examples are given to illustrate the various dilemmas the user of this atlas may face when scoring the rheumatoid hand and suggestions are made to assist correct interpretation of what can be very complex images.

Østergaard M, Edmonds J, McQueen F, Peterfy C, Lassere M, Ejbjerg B, Bird P, Emery P, Genant H, Conaghan P. · Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Kettegaard alle 30, DK-2650 Hvidovre, Denmark. · Ann Rheum Dis. · Pubmed #15647420 links to  free full text

Abstract: This article gives a short overview of the development and characteristics of the OMERACT rheumatoid arthritis MRI scoring system (RAMRIS), followed by an introduction to the use of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. With this atlas, MRIs of wrist and metacarpophalangeal joints of patients with rheumatoid arthritis can be scored for synovitis, bone oedema, and bone erosion, guided by standard reference images.

Ejbjerg B, McQueen F, Lassere M, Haavardsholm E, Conaghan P, O'Connor P, Bird P, Peterfy C, Edmonds J, Szkudlarek M, Genant H, Emery P, Østergaard M. · Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Copenhagen, Denmark. · Ann Rheum Dis. · Pubmed #15647419 links to  free full text

Abstract: This paper presents the wrist joint MR images of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0-3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system--that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0-3 of bone oedema are illustrated, and for bone erosion, grades 0-3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system.

Conaghan P, Bird P, Ejbjerg B, O'Connor P, Peterfy C, McQueen F, Lassere M, Emery P, Shnier R, Edmonds J, Østergaard M. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #15647417 links to  free full text

Abstract: This paper presents the metacarpophalangeal (MCP) joint magnetic resonance images of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. The illustrations include synovitis in the MCP joints (OMERACT RA magnetic resonance imaging scoring system (RAMRIS), grades 0-3), bone oedema in the metacarpal head and the phalangeal base (grades 0-3), and bone erosion in the metacarpal head and the phalangeal base (grades 0-3, and examples of higher grades). The presented reference images can be used to guide scoring of MCP joints according to the OMERACT RA MRI scoring system.

Conaghan P, Lassere M, Østergaard M, Peterfy C, McQueen F, O'Connor P, Bird P, Ejbjerg B, Klarlund M, Shnier R, Genant H, Emery P, Edmonds J. · Academic Unit of Musculoskeletal and Rehabilitation Medicine, University of Leeds, UK. · J Rheumatol. · Pubmed #12784420 No free full text.

Abstract: The aim of this multireader, multicenter study was to assess the inter-reader reliability of the score in the assessment of disease status and progression. The exercise involved 10 sets of metacarpophalangeal (MCP, 2nd to 5th) joints and 10 sets of wrist magnetic resonance images that were scored by experienced readers from 5 international centers. Synovitis was scored for each site using a global score (0-3). Bone abnormalities were assessed at 8 MCP joint sites and 15 wrist sites according to proportion of bone volume (0-10 for erosions and defects and 0-3 for edema). Intraclass correlation coefficients (ICC) and smallest detectable differences for synovitis, erosions, and edema were acceptable, although better for status scores than progression scores. The agreement for MCP joints was better than wrists. Limited variation in the images for some findings resulted in low ICC. Bone defects had the poorest agreement and have been omitted from new scoring recommendations. Despite limited training, multicenter readers demonstrated acceptable levels of agreement.

Lassere M, McQueen F, Østergaard M, Conaghan P, Shnier R, Peterfy C, Klarlund M, Bird P, O'Connor P, Stewart N, Emery P, Genant H, Edmonds J. · Department of Rheumatology, St. George Hospital, University of New South Wales, Sydney, Australia. · J Rheumatol. · Pubmed #12784419 No free full text.

Abstract: We examined inter-reader agreement of the revised OMERACT 5 Rheumatoid Arthritis MRI Score (RAMRIS v3). Magnetic resonance (MR) images of 10 sets of metacarpophalangeal (MCP) joints 2-5 and 8 sets of rheumatoid arthritis (RA) wrists [1.5 T, coronal and axial T1 and T2 spin-echo, +/- fat saturation (FS), +/- intravenous gadolinium (Gd)] were scored for (1) synovitis using a global score (0-3) and a direct measurement of synovial thickness (mm) and (2) three bone lesions: erosions, defects and edema, (score 0-10 by the volume of the lesion as a proportion of the "assessed bone volume" by 10% increments). Six readers from 5 multinational centers performed all scoring. Three statistical methods were used to analyze the data: (1) single-measure fixed effects intraclass correlations (sICC) and average-measure fixed effects ICC (avICC), (2) percentage exact and close agreement, and (3) the smallest detectable difference (SDD). The sICC were moderate to good (between 0.60 and 0.91) for half of the joint sites for the 2 synovitis scoring methods, and for bone erosions and bone edema. After adjusting for 6 readers, the avICC was very good to excellent (0.80-0.98) for two-thirds of the joint sites by lesion, excluding bone defects that performed relatively poorly, primarily because few readers scored these lesions. The aggregated scores with the best reliability were those with a wide range of scores, high ICC, low SDD, and low percentage SDD (< 33%). The metacarpophalangeal (MCP) bone erosion (sICC 0.58, avICC 0.89, %SDD +/- 27), wrist bone erosion scores (0.72, 0.94, +/- 31%), the wrist synovitis global (0.74, 0.94, +/- 32%), and synovial maximal thickness (0.6, 0.94, +/- 32%) met these conditions. MCP joint synovitis global (0.76, 0.95, +/-35%), MCP joint bone edema (0.63, 0.91, +/- 34%), and wrist bone edema (0.78, 0.95, +/- 38%) performed marginally less well. Bone defects performed poorly (MCP joint 0.18, 0.46, +/- 56%; wrist 0.06, 0.24, +/- 55%). The revised OMERACT 5 RAMRIS has acceptable inter-reader reliability for measures of disease activity (synovitis global and bone edema scores) and damage (bone erosion score). Whether the score is sensitive to change will be determined by its performance in longitudinal and intervention studies.

Ponchel F, Morgan AW, Bingham SJ, Quinn M, Buch M, Verburg RJ, Henwood J, Douglas SH, Masurel A, Conaghan P, Gesinde M, Taylor J, Markham AF, Emery P, van Laar JM, Isaacs JD. · Molecular Medicine Unit, The University of Leeds, St James's University Hospital, United Kingdom. · Blood. · Pubmed #12393721 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4(+) T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RB(bright)CD45RA(+)CD62L(-) by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.

Green M, Marzo-Ortega H, McGonagle D, Wakefield R, Proudman S, Conaghan P, Gooi J, Emery P. · University of Leeds, UK. · Arthritis Rheum. · Pubmed #10524691 links to  free full text

Abstract: OBJECTIVE: To determine the factors that predict clinical outcome at 6 months for patients with mild, early inflammatory arthritis. METHODS: Sixty-three patients with mild, untreated, early arthritis were given a single dose of corticosteroids at presentation. Administration was intramuscular if disease was polyarticular (n = 53) or intraarticular if patients had <5 synovitic joints (n = 10). The primary outcome measure was clinical disease remission or persistence of arthritis at 6 months following injection. RESULTS: At 6 months following injection, 49 of the 63 patients (78%) had persistent inflammatory joint disease. The other 14 (22%) had clinical disease remission. Regression analysis showed that only disease duration was significantly associated with persistent arthritis (P < 0.05). The other significant factor (by chi-square test) was the presence of the shared epitope (SE). Of the patients fulfilling the American College of Rheumatology (ACR) criteria at presentation (51% of the total), 53% with disease duration of < or = 12 weeks at presentation had persistent disease 6 months later, compared with 94% of those who presented with disease duration of >12 weeks. CONCLUSION: The strongest predictor of persistent disease was a disease duration of >12 weeks. Rheumatoid factor and SE were also predictors to a lesser extent. Patients who both fulfilled the ACR classification criteria for rheumatoid arthritis (RA) and had a short disease duration included some with an excellent prognosis. Therefore, 12 weeks may be a more appropriate disease duration to use for the RA classification criteria. Administering a bolus of corticosteroids may be a useful diagnostic/therapeutic approach.