Rheumatoid Arthritis: Wakefield RJ

Wakefield RJ, Gibbon WW, Emery P. · No affiliation provided · Rheumatology (Oxford). · Pubmed #10325656 links to  free full text

This publication has no abstract.

Keen HI, Lavie F, Wakefield RJ, D'Agostino MA, Hammer HB, Hensor E, Pendleton A, Kane D, Guerini H, Schueller-Weidekamm C, Kortekaas MC, Birrel F, Kloppenburg M, Stamm T, Watt I, Smolen JS, Maheu E, Dougados M, Conaghan PG. · Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #17704062 No free full text.

Abstract: OBJECTIVES: Painful osteoarthritis (OA) of the hand is common and a validated ultrasound (US) scoring system would be valuable for epidemiological and therapeutic outcome studies. US is increasingly used to assess peripheral joints, though most of the US focus in rheumatic diseases has been on rheumatoid arthritis. We aimed to develop a preliminary US hand OA scoring system, initially focusing on relevant pathological features with potentially high reliability. METHODS: A group of experts in the fields of OA, US and novel tool development agreed on domains and suggested scaling of the items to be used in US hand OA scoring systems. A multi-observer reliability exercise was then performed to evaluate the draft items. RESULTS: Synovitis (grey scale and Power Doppler) and osteophytes (representing activity and damage domains) were included and evaluated as the initial components of the scoring system. All three features were evaluated for their presence/absence and if present were scored using a 1-3 scale. The reliability exercise demonstrated intra-reader kappa values of 0.444-1.0, 0.211-1.0 and 0.087-1.0 for grey scale synovitis, power Doppler and osteophytes respectively. Inter-reader reliability kappa values were 0.398, 0.327 and 0.530 grey-scale synovitis, power Doppler and osteophytes respectively. Without extensive standardisation, both intra- and inter-reader reliability were moderately good. CONCLUSIONS: The draft scoring system demonstrated substantive to almost perfect percentage exact agreement on the presence/absence of the selected OA features and moderate to substantive percentage exact agreement on semi-quantitative grading. This preliminary process provides a good basis from which to further develop an US outcome tool for hand OA that has the potential to be utilised in multicentre clinical trials.

Joshua F, Lassere M, Bruyn GA, Szkudlarek M, Naredo E, Schmidt WA, Balint P, Filippucci E, Backhaus M, Iagnocco A, Scheel AK, Kane D, Grassi W, Conaghan PG, Wakefield RJ, D'Agostino MA. · Department of Rheumatology, St. George Hospital, University of NSW, Sydney, Australia. · J Rheumatol. · Pubmed #17407235 No free full text.

Abstract: This report presents the results of a recent systematic review performed by the OMERACT Ultrasound Group on the metric properties of ultrasound for the detection of synovitis in inflammatory arthritis. Reviews were conducted for the hand, wrist, elbow, shoulder, knee, ankle, and foot; most reports were related to the hand and knee, and the most common disease process was rheumatoid arthritis. The review highlights the current gaps in the literature, including a lack of reliability data with respect to intra-occasion and intra- and inter-reader reliability. Current work by our group is addressing these issues.

Keen HI, Brown AK, Wakefield RJ, Conaghan PG. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. · Rheum Dis Clin North Am. · Pubmed #16287592 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder primarily affecting the synovium and is characterized by destruction of bone and cartilage. Early diagnosis and treatment of RA can improve disease outcomes substantially. Magnetic resonance imaging and musculoskeletal ultrasonography may facilitate early diagnosis and aid the targeting of intensive therapy. Magnetic resonance imaging and musculoskeletal ultrasonography also are able to monitor temporal changes in disease activity (ie, synovitis) and damage (ie, erosions). These imaging modalities are likely to be increasingly used in the management of early rheumatoid arthritis to ensure the best patient outcomes, although more work is required to determine their optimal roles.

Brown AK, Wakefield RJ, Conaghan PG, Karim Z, O'Connor PJ, Emery P. · Academic Unit of Musculoskeletal Disease, Department of Rheumatology, University of Leeds, Leeds General Infirmary, UK. · Clin Exp Rheumatol. · Pubmed #15552510 No free full text.

Abstract: Imaging techniques such as musculoskeletal ultrasonography (MUS) and magnetic resonance imaging (MRI) are playing an increasingly important role in the assessment of patients with inflammatory arthritis. Such modalities are now used routinely in the evaluation of joint, tendon and soft tissue inflammation and bone damage in many early arthritis clinics. They have the ability to directly visualise, characterise and quantify the earliest inflammatory changes and have proved not only to be useful additional complimentary clinical tools to improve the speed and accuracy of diagnosis, direct appropriate treatment, monitor response to therapy, measure disease progression and outcome but also continue to contribute to our understanding of disease pathogenesis. These imaging methods may therefore offer a significant advantage as they endorse the principles of early diagnosis and optimal targeted therapy essential to providing the most favourable long term outcome for patients with inflammatory arthritis. This article reviews the current evidence supporting the role of MUS and MRI in the assessment of patients with inflammatory arthritis.

Wakefield RJ, Conaghan PG, Jarrett S, Emery P. · Academic Department of Musculoskeletal Medicine, Leeds General Infirmary, UK. · Curr Opin Rheumatol. · Pubmed #15201608 No free full text.

Abstract: New imaging techniques such as ultrasound and MRI are likely to play increasing roles in the future management of patients with inflammatory arthritis, particularly those with rheumatoid arthritis and spondyloarthropathies. Ultrasound has a number of distinct advantages including its ability to scan multiple joints, safety, and immediately availability in clinic. MRI, however, is more sensitive and has a greater field of view because of its tomographic nature. Both modalities have the added advantage over radiography in that they can image soft tissue as well as bone. Dual X-ray absorptiometry already has an established role to play in the assessment of osteoporosis, but new techniques such as digital radiogrametry, quantitative CT, and ultrasound potentially will have a more important role to play in the future.

Wakefield RJ, Kong KO, Conaghan PG, Brown AK, O'Connor PJ, Emery P. · Academic Department of Musculoskeletal Medicine, General Infirmary at Leeds, Leeds, United Kingdom. · Clin Exp Rheumatol. · Pubmed #14969049 No free full text.

Abstract: Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.

Gibbon WW, Wakefield RJ. · Department of Sports Medicine Leeds Metropolitan University, United Kingdom. · Radiol Clin North Am. · Pubmed #10442072 No free full text.

Abstract: US may be used effectively to diagnose and treat a wide range of musculoskeletal inflammatory conditions. It is likely that its usage will increase with regards to such conditions especially in the management of rheumatology clinic patients.

Wakefield RJ, Freeston JE, Hensor EM, Bryer D, Quinn MA, Emery P. · Chapel Allerton Hospital, Leeds, UK. · Arthritis Rheum. · Pubmed #18050231 links to  free full text

This publication has no abstract.

Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, Wakefield RJ, O'Connor PJ, Emery P. · Chapel Allerton Hospital, University of Leeds, Leeds, UK. · Arthritis Rheum. · Pubmed #17133543 links to  free full text

Abstract: OBJECTIVE: More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. METHODS: We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. RESULTS: Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. CONCLUSION: Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.

Conaghan PG, O'Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon WW, Quinn M, Karim Z, Green MJ, Proudman S, Isaacs J, Emery P. · University of Leeds and Leeds General Infirmary, Leeds, UK. · Arthritis Rheum. · Pubmed #12528105 links to  free full text

Abstract: OBJECTIVE: To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis (RA). METHODS: Forty patients with early, untreated RA underwent gadolinium-enhanced magnetic resonance imaging (MRI) of the second through fifth metacarpophalangeal joints of the dominant hand at presentation, 3 months, and 12 months. In the first phase (0-3 months), patients were randomized to receive either methotrexate alone (MTX) or MTX and intraarticular corticosteroids (MTX + IAST) into all joints with clinically active RA. The MTX-alone group received no further corticosteroids until the second phase (3-12 months), when both groups received standard therapy. RESULTS: In the first phase, MTX + IAST reduced synovitis scores more than MTX alone. There were significantly fewer joints with new erosions on MRI in the former group compared with the latter. During the second phase, the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI. In both phases, there was a close correlation between the degree of synovitis and the number of new erosions, with the area under the curve for MRI synovitis the only significant predictor of bone damage progression. In individual joints, there was a threshold effect on new bone damage related to the level of synovitis; no erosions occurred in joints without synovitis. CONCLUSION: In early RA, synovitis appears to be the primary abnormality, and bone damage occurs in proportion to the level of synovitis but not in its absence. In the treatment of patients with RA, outcome measures and therapies should focus on synovitis.

Proudman SM, Conaghan PG, Richardson C, Griffiths B, Green MJ, McGonagle D, Wakefield RJ, Reece RJ, Miles S, Adebajo A, Gough A, Helliwell P, Martin M, Huston G, Pease C, Veale DJ, Isaacs J, van der Heijde DM, Emery P. · University of Leeds, UK. · Arthritis Rheum. · Pubmed #10943871 links to  free full text

Abstract: OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Kiely PD, Brown AK, Edwards CJ, O'Reilly DT, Ostör AJ, Quinn M, Taggart A, Taylor PC, Wakefield RJ, Conaghan PG. · Department of Rheumatology, St Georges Healthcare NHS Trust, London, UK. · Rheumatology (Oxford). · Pubmed #19401359 No free full text.

Abstract: OBJECTIVE: RA has a substantial impact on both patients and healthcare systems. Our objective is to advance the understanding of modern management principles in light of recent evidence concerning the condition's diagnosis and treatment. METHODS: A group of practicing UK rheumatologists formulated contemporary management principles and clinical practice recommendations concerning both diagnosis and treatment. Areas of clinical uncertainty were documented, leading to research recommendations. RESULTS: A fundamental concept governing treatment of RA is minimization of cumulative inflammation, referred to as the inflammation-time area under the curve (AUC). To achieve this, four core principles of management were identified: (i) detect and refer patients early, even if the diagnosis is uncertain: patients should be referred at the first suspicion of persistent inflammatory polyarthritis and rheumatology departments should provide rapid access to a diagnostic and prognostic service; (ii) treat RA immediately: optimizing outcomes with conventional DMARDs and biologics requires that effective treatment be started early-ideally within 3 months of symptom onset; (iii) tight control of inflammation in RA improves outcome: frequent assessments and an objective protocol should be used to make treatment changes that maintain low-disease activity/remission at an agreed target; (iv) consider the risk-benefit ratio and tailor treatment to each patient: differing patient, disease and drug characteristics require long-term monitoring of risks and benefits with adaptations of treatments to suit individual circumstances. CONCLUSION: These principles focus on effective control of the inflammatory process in RA, but optimal uptake may require changes in service provision to accommodate appropriate care pathways.

Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, Hensor E, Wakefield RJ, O'Connor PJ, Emery P. · Leeds Institute of Molecular Medicine, University of Leeds, and Chapel Allerton Hospital, Leeds, UK. · Arthritis Rheum. · Pubmed #18821687 No free full text.

Abstract: OBJECTIVE: Achieving remission is the aim of treatment in rheumatoid arthritis (RA). This should represent minimal arthritis activity and ensure optimal disease outcome. However, we have previously demonstrated a high prevalence of imaging-detected synovial inflammation in RA patients who were in clinical remission. The purpose of this study was to evaluate the long-term significance of subclinical synovitis and its relationship to structural outcome. METHODS: We studied 102 RA patients receiving conventional treatment who had been judged by their consultant rheumatologist to be in remission, as well as 17 normal control subjects. Subjects underwent clinical, laboratory, functional, and quality of life assessments over 12 months. In addition to standard radiography of the hands and feet, imaging of the hands and wrists was performed with musculoskeletal ultrasonography (US) and conventional 1.5 T magnetic resonance imaging (MRI) at baseline and 12 months, using validated acquisition and scoring techniques. RESULTS: Despite their being in clinical remission, 19% of the patients displayed deterioration in radiographic joint damage over the study period. Scores on musculoskeletal US synovial hypertrophy, power Doppler (PD), and MRI synovitis assessments in individual joints at baseline were significantly associated with progressive radiographic damage (P=0.032, P<0.001, and P=0.002, respectively). Furthermore, there was a significant association between the musculoskeletal US PD score at baseline and structural progression over 12 months in totally asymptomatic metacarpophalangeal joints (P=0.004) and 12 times higher odds of deterioration in joints with increased PD signal (odds ratio 12.21, P<0.001). CONCLUSION: Subclinical joint inflammation detected by imaging techniques explains the structural deterioration in RA patients in clinical remission who are receiving conventional therapy. Our findings reinforce the utility of imaging for the accurate evaluation of disease status and the prediction of structural outcome.

Bruyn GA, Naredo E, Möller I, Moragues C, Garrido J, de Bock GH, d'Agostino MA, Filippucci E, Iagnocco A, Backhaus M, Swen WA, Balint P, Pineda C, Milutinovic S, Kane D, Kaeley G, Narvaez FJ, Wakefield RJ, Narvaez JA, de Augustin J, Schmidt WA. · Department of Rheumatology, Medisch Centrum Leeuwarden, 8934 AD Leeuwarden, Leeuwarden, The Netherlands. · Ann Rheum Dis. · Pubmed #18390570 No free full text.

Abstract: OBJECTIVE: To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI. METHODS: A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated. RESULTS: Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively. CONCLUSIONS: US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.

Wakefield RJ, Freeston JE, O'Connor P, Reay N, Budgen A, Hensor EM, Helliwell PS, Emery P, Woodburn J. · Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK. · Ann Rheum Dis. · Pubmed #18258710 No free full text.

Abstract: OBJECTIVES: The aim of this pilot study was to compare clinical examination (CE) and ultrasound (US) with high field MRI (as the reference standard) for the detection of rearfoot and midtarsal joint synovitis and secondly tenosynovitis of the ankle tendons in patients with established rheumatoid arthritis (RA). METHODS: Patients with RA (as determined by the modified American College of Rheumatology (ACR) criteria) with symptoms of midfoot and rearfoot disease were recruited. Demographic data were collected. All underwent CE, US and high field MRI (with intravenous gadolinium contrast) of their right foot. Percentage exact agreement (PEA), sensitivity and specificity were calculated for CE and US when compared to MRI. Inter-reader reliability for CE and US was also assessed. RESULTS: Compared to the gold standard of MRI, for CE (joint synovitis) the ranges for sensitivity, specificity and PEA were 55-83%, 23-46% and 46-60%, and for US were 64-89%, 60-80% and 64-78%, respectively. Compared to the gold standard of MRI, for CE (tenosynovitis) the ranges for sensitivity, specificity and PEA were 0-100%, 20-91% and 55-91%, and for US were 0-67%, 86-100% and 59-86%, respectively. CONCLUSION: CE was sensitive but US more specific in identifying hindfoot pathology in RA when compared to the reference standard of MRI. There was poor interobserver variability between ultrasonographers suggesting a need for standardisation of acquisition and interpretation of US images of the hindfoot.

Wakefield RJ, O'Connor PJ, Conaghan PG, McGonagle D, Hensor EM, Gibbon WW, Brown C, Emery P. · Chapel Allerton Hospital, Leeds, UK. · Arthritis Rheum. · Pubmed #17907233 links to  free full text

Abstract: OBJECTIVE: To investigate the frequency and distribution of finger tenosynovitis in patients with early, untreated rheumatoid arthritis (RA) using gray-scale ultrasound (US) and magnetic resonance imaging (MRI). METHODS: Fifty patients underwent US and MRI of metacarpophalangeal (MCP) joints 2-5. Twenty healthy controls underwent US only. Flexor and extensor involvement was documented for each joint. Intrareader reliability (IRR) was calculated by rereading static images. RESULTS: Flexor tenosynovitis was found in 57 (28.5%) of 200 joints in 24 (48%) of 50 patients on US compared with 128 (64%) of 200 joints in 41 (82%) of 50 patients on MRI. Periextensor tenosynovitis was found in 14 (7%) joints in 9 (18%) patients on US compared with 80 (40%) joints in 36 (72%) patients on MRI. No controls had imaging tenosynovitis. Using MRI as the gold standard, the sensitivity, specificity, and negative and positive predictive values for US were 0.44, 0.99, 0.49, and 0.98, respectively, for flexor tenosynovitis and 0.15, 0.98, 0.63, and 0.86 for extensor tenosynovitis, respectively. The IRR was 0.85 and 0.8 for US and MRI, respectively. The most frequently involved joints on US and MRI were the second and third MCP joints. CONCLUSION: This is the first study to compare US and MRI for the detection of tenosynovitis in the fingers of patients with early untreated RA. Tenosynovitis was found to be common using both modalities, with MRI being more sensitive. A negative US scan does not exclude inflammation and an MRI should be considered. Further work is recommended to standardize definitions and image acquisition for both US and MRI images.

Wakefield RJ, D'Agostino MA, Iagnocco A, Filippucci E, Backhaus M, Scheel AK, Joshua F, Naredo E, Schmidt WA, Grassi W, Moller I, Pineda C, Klauser A, Szkudlarek M, Terslev L, Balint P, Bruyn GA, Swen WA, Jousse-Joulin S, Kane D, Koski JM, O'Connor P, Milutinovic S, Conaghan PG, Anonymous00480. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #17407236 No free full text.

Abstract: Ultrasound (US) is a relatively new imaging modality in rheumatology that offers great potential as a diagnostic and management tool. In 2004, an OMERACT Ultrasound Special Interest Group was formed to address the metric qualities of US as a potential outcome measure. A preliminary systematic review highlighted the deficiencies in the literature, particularly with regard to the reliability of interpreting and acquiring images; as a consequence, a number of exercises were proposed to address these issues. This report describes a series of iterative studies that have resulted in improved intra- and inter-reader reliability for detecting and scoring synovitis from both static and real-time images of the hand joints of patients with rheumatoid arthritis. The reliability of acquiring images was also enhanced using standardized positions. Future studies will assess the value of US in clinical trials.

Karim Z, Quinn MA, Wakefield RJ, Brown AK, Green MJ, Hensor EM, Conaghan PG, Emery P. · Academic Unit of Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK. · Ann Rheum Dis. · Pubmed #17127687 No free full text.

Abstract: BACKGROUND: Hand pain with stiffness is a common clinical presentation to early arthritis clinics, with outcome varying from resolution to the development of rheumatoid arthritis. OBJECTIVE: To assess the response and predictors of response to intramuscular methylprednisolone (MP) and hydroxychloroquine (HCQ) using a standardised treatment protocol. METHODS: Patients with inflammatory hand pain (IHP), defined as predominantly hand pain and morning stiffness of at least 30 min duration, received a standardised assessment prior to receiving intramuscular MP. Response (primary outcome) at 4 weeks was a 50% improvement in symptoms as perceived by the patient; responders who relapsed received repeat intramuscular MP and HCQ. RESULTS: 102 patients were recruited, of which 21% were rheumatoid factor (RF) positive, 23% had clinical synovitis, 25% had raised C-reactive protein level and 55% had ultrasound-detected synovitis. 73% responded, with associated significant reductions in morning stiffness, Health Assessment Questionnaire, painful and tender joint counts, and visual analogue scores (p < or = 0.006 for all). Ultrasound-detected synovitis (p<0.001) and RF (p = 0.04), but not clinical synovitis (p = 0.74), were significantly associated with response to intramuscular MP. 86% who remained on HCQ long term reported a benefit. CONCLUSIONS: Patients with IHP have significant improvement in symptoms and function following intramuscular MP. Further placebo-controlled trials are required to assess the role of intramuscular MP and ultrasonography in managing this patient group.

Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D'Agostino MA, Sanchez EN, Iagnocco A, Schmidt WA, Bruyn GA, Bruyn G, Kane D, O'Connor PJ, Manger B, Joshua F, Koski J, Grassi W, Lassere MN, Swen N, Kainberger F, Klauser A, Ostergaard M, Brown AK, Machold KP, Conaghan PG, Anonymous00384. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #16331793 No free full text.

Abstract: Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis.

Haugeberg G, Green MJ, Quinn MA, Marzo-Ortega H, Proudman S, Karim Z, Wakefield RJ, Conaghan PG, Stewart S, Emery P. · Academic Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK. · Ann Rheum Dis. · Pubmed #16284095 links to  free full text

Abstract: OBJECTIVES: (1) To examine the change in regional bone mineral density (BMD), including the hands, and assess its role as a predictor of outcome in patients presenting with an early undifferentiated inflammatory arthritis; (2) to examine for associations with the changes in hand BMD. METHODS: 74 patients with undifferentiated hand arthritis of less than 12 months' duration were examined at baseline and then at three, six, and 12 months follow up, including BMD measurement of the femoral neck, spine (L2-4), and the whole hands using dual energy absorptiometry (DXA). RESULTS: During the study, 13 patients were diagnosed as having rheumatoid arthritis, 19 as having inflammatory non-rheumatoid joint disorders, and 42 as having non-inflammatory joint disorders. At the femoral neck and lumbar spine no significant bone loss was seen in any of the three subgroups. At the 12 months follow up the mean (95% confidence interval) hand BMD loss in the patients with rheumatoid arthritis was -4.27% (-1.41 to -7.13); in the inflammatory non-rheumatoid group, -0.49% (-1.33 to +0.35); and in the non-inflammatory joint disorder group, -0.87% (-1.51 to -0.23). In a multivariate linear regression model (including age, rheumatoid factor, mean C reactive protein, mean HAQ score, and cumulative glucocorticoid dose), only mean C reactive protein (p<0.001) and rheumatoid factor (p = 0.04) were independently associated with change in hand BMD during follow up. CONCLUSIONS: Hand DXA provides a very sensitive tool for measuring bone loss in early rheumatoid arthritis and may be useful in identifying patients at high risk of developing progressive disease. Further studies are needed to evaluate the role of hand bone loss as a prognostic factor and outcome measure in rheumatoid arthritis.

Quinn MA, Green MJ, Marzo-Ortega H, Proudman S, Karim Z, Wakefield RJ, Conaghan PG, Emery P. · Royal Adelaide Hospital, Adelaide, Australia. · Arthritis Rheum. · Pubmed #14613264 links to  free full text

Abstract: OBJECTIVE: Inflammatory arthritis of the hands is a frequent clinical presentation with a variable outcome. Patients not satisfying the classification criteria for recognized arthritides are described as having undifferentiated inflammatory arthritis, for which there are no accepted therapeutic algorithms. This study assessed the clinical outcome of patients with undifferentiated arthritis of the hands after use of a treatment algorithm, and evaluated the prognostic features in these patients. METHODS: One hundred consecutive patients with undifferentiated arthritis of the hands were assessed following use of a pragmatic treatment algorithm that was based on clinical presentation and response to treatment. The following standard step-up treatment protocol was used: 1) nonsteroidal antiinflammatory drugs (NSAIDs), 2) a single dose of corticosteroid administered by either intramuscular or intraarticular injection, and 3) disease-modifying antirheumatic drugs (DMARDs). Patients with specific rheumatologic diagnoses were excluded. The primary outcome was persistence of synovitis at 12 months. RESULTS: Seventy-eight percent of patients received NSAIDs, 72% received corticosteroids, and 30% received DMARD therapy. Among patients who had synovitis at 12 months, the prevalence of rheumatoid factor (RF) seropositivity, swollen joints, and synovitis at baseline was greater than in those without persistent synovitis. Logistic regression analysis showed baseline investigations to be poor predictors of subsequent DMARD use, with the best predictor being persistence of synovitis at 12 weeks. Rheumatoid arthritis (RA) developed in 14 patients. Logistic regression analysis showed that significant predictors of RA were RF seropositivity and the painful joint count at baseline. No patient who experienced resolution of synovitis by 12 weeks had persistent synovitis that subsequently required DMARD therapy. Only 13% of patients entered remission. Early resolution of synovitis was associated with an excellent prognosis. CONCLUSION: Undifferentiated arthritis of the hands is not a benign condition, with 30% of patients receiving DMARD therapy by 12 months and low remission rates. Results of the clinical assessment at 12 weeks is the single best predictor of future therapy. This study provides background data for use in determining future therapeutic interventions.

Woodburn J, Udupa JK, Hirsch BE, Wakefield RJ, Helliwell PS, Reay N, O'Connor P, Budgen A, Emery P. · Rheumatology & Rehabilitation Research Unit, University of Leeds, Leeds, UK. · Arthritis Rheum. · Pubmed #12483720 links to  free full text

Abstract: OBJECTIVE: To compare in vivo the 3-dimensional (3-D) geometric architecture of the subtalar and midtarsal joints in normal and rheumatoid arthritic (RA) feet, using magnetic resonance imaging (MRI) analysis. METHODS: MRI was performed on 23 patients with RA, all of whom had disease activity in the subtalar and/or midtarsal joints. Image processing techniques were used to create 3-D reconstructions of the calcaneus (C), cuboid (c), navicular (N), and talus (T) bones. Twenty-four standard architectural parameters were measured from the reconstructions and were compared with data from 10 normal subjects. These parameters defined both 3-D distance and angular relationships among the 4 bones studied. Pattern classification techniques were used to establish a geometric architecture foot profile for the RA patients. The degree of individual patient fit to the new RA foot profile and to profiles for normal, pes planus, and pes cavus foot types was derived. Logistic regression was used to examine the relationship of foot architecture to inflammatory disease characteristics and physical examination variables. RESULTS: Subtalar or midtarsal pain was reported by all 23 patients, and 22 of the 23 patients presented with >/=1 clinical feature of pes planovalgus deformity. In 21 patients, ultrasonography revealed synovitis at >/=1 tarsal joint or surrounding tendon. In the RA group, the normalized distances between the geometric centroids were significantly closer for bone pairs Cc and cT and significantly distracted for bone pair CN compared with the distances in normal subjects. In RA patients (versus normal subjects), the angles subtended at the bone centroids were significantly decreased in 3 bone groups (CNc, TCN, and TNc) and significantly increased in 3 bone groups (CcN, CcT, NTc). The angles formed between the major principal axes of bone pairs CT and cT were significantly increased in RA patients compared with those in normal subjects. Pattern classification defined 11 RA feet as having normal structure and 12 as having abnormal structure. However, the abnormal feet did not fit consistently with structures defined for RA, pes planus, or pes cavus foot types. Logistic regression demonstrated that subtalar joint synovitis was the only predictive factor for abnormal subtalar and midtarsal architecture (odds ratio 19.2, 95% confidence interval 1.77-200.0). CONCLUSION: This unique 3-D MRI-based technique successfully quantified the effects of RA on the geometric architecture of the foot and the patient-specific nature of these changes. This technique can be used to provide logical therapy for correction.

Wakefield RJ, Gibbon WW, Conaghan PG, O'Connor P, McGonagle D, Pease C, Green MJ, Veale DJ, Isaacs JD, Emery P. · University of Leeds, UK. · Arthritis Rheum. · Pubmed #11145034 links to  free full text

Abstract: OBJECTIVE: The ability to make an early, accurate diagnosis of rheumatoid arthritis (RA) has become increasingly important with the availability of new, expensive, and targeted therapies. However, plain radiography, the traditional method of detecting the characteristic bone erosions and an important adjunct in establishing a diagnosis of RA, is known to be insensitive. This study compared sonography, a modern imaging technique, with conventional radiography for the detection of erosions in the metacarpophalangeal (MCP) joints of patients with RA. METHODS: One hundred RA patients (including 40 with early disease) underwent posteroanterior radiography and sonography of the MCP joints of the dominant hand. Twenty asymptomatic control subjects also underwent sonography. Erosion sites were recorded and subsequently compared using each modality. Magnetic resonance imaging (MRI) was performed on the second MCP joint in 25 patients with early RA to confirm the pathologic specificity of sonographic erosions. Intraobserver reliability of sonography readings was assessed using video recordings of 55 MCP joint scans of RA patients, and interobserver reliability was assessed by comparing 160 MCP joint scans performed sequentially by 2 independent observers. RESULTS: Sonography detected 127 definite erosions in 56 of 100 RA patients, compared with radiographic detection of 32 erosions (26 [81%] of which coincided with sonographic erosions) in 17 of 100 patients (P < 0.0001). In early disease, sonography detected 6.5-fold more erosions than did radiography, in 7.5-fold the number of patients. In late disease, these differences were 3.4-fold and 2.7-fold, respectively. On MRI, all sonographic erosions not visible on radiography (n = 12) corresponded by site to MRI abnormalities. The Cohen-kappa values for intra- and interobserver reliability of sonography were 0.75 and 0.76, respectively. CONCLUSION: Sonography is a reliable technique that detects more erosions than radiography, especially in early RA. Sonographic erosions not seen on radiography corresponded to MRI bone abnormalities. This technology has potential in the management of patients with early RA/inflammatory arthritis and is likely to have major implications for the future practice of rheumatology.

Bruyn GA, Iagnocco A, Naredo E, Wakefield RJ, Schmidt WA. · No affiliation provided · Arthritis Rheum. · Pubmed #15457483 links to  free full text

This publication has no abstract.