Rheumatoid Arthritis: Robinson E

McQueen FM, Benton N, Perry D, Crabbe J, Robinson E, Yeoman S, McLean L, Stewart N. · Auckland District Health Board and Auckland University, Auckland, New Zealand. · Arthritis Rheum. · Pubmed #12847674 links to  free full text

Abstract: OBJECTIVE: Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. METHODS: We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. RESULTS: At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44). CONCLUSION: MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease.

Dalbeth N, Smith T, Gray S, Doyle A, Antill P, Lobo M, Robinson E, King A, Cornish J, Shalley G, Gao A, McQueen FM. · Bone Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand. · Ann Rheum Dis. · Pubmed #18765428 No free full text.

Abstract: OBJECTIVES: Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. METHODS: Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. RESULTS: The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). CONCLUSIONS: The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone.

McQueen FM, Gao A, Ostergaard M, King A, Shalley G, Robinson E, Doyle A, Clark B, Dalbeth N. · Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, Park Rd, Private Bag 92019 Auckland, New Zealand. · Ann Rheum Dis. · Pubmed #17491098 No free full text.

Abstract: OBJECTIVES: MRI bone oedema has been observed in early and advanced RA and may represent a cellular infiltrate (osteitis) in subchondral bone. We studied MRI scans from RA patients undergoing surgery, seeking to identify regions of bone oedema and examine its histopathological equivalent in resected bone. METHODS: Preoperative contrast-enhanced MRI scans were obtained in 11 RA patients scheduled for orthopaedic surgery to the hands/wrists or feet. In 9, MRI scans were scored by 2 readers for bone oedema (RAMRIS system). Its distribution with respect to surgical site was investigated. In 4 patients, 7 bone samples were examined for a cellular infiltrate, and this was compared with MRI bone oedema, scored for spatial extent and intensity. RESULTS: Inter-reader intraclass correlation coefficients for bone oedema were 0.51 (all sites) and 0.98 (bone samples for histology). Bone oedema was observed at 60% of surgical sites vs 38% of non-surgical sites. High-grade bone oedema (score >/=50% maximum) was strongly associated with the surgical field (OR 9.3 (3.5 to 24.2), p<0.0001). Bone oedema scores correlated with pain (r = 0.67, p = 0.048) and CRP (r = 0.86, p = 0.01). In 4 of the 7 bone samples, there was concordance between bone oedema and subchondral osteitis. In 3, there was no MRI bone oedema, and osteitis was "slight". CONCLUSION: High-grade MRI bone oedema was common within the field of intended surgery and associated with pain. There was concordance between the presence and severity of MRI bone oedema and osteitis on histology, with an MRI threshold effect due to differences in image resolution.

Zheng S, Robinson E, Yeoman S, Stewart N, Crabbe J, Rouse J, McQueen FM. · Department of Molecular Medicine, Auckland School of Medicine, Auckland University, Private Bag 92019, Auckland, New Zealand. · Ann Rheum Dis. · Pubmed #16219706 links to  free full text

Abstract: OBJECTIVE: To investigate the role of early magnetic resonance imaging (MRI) of the wrist in predicting functional outcome in rheumatoid arthritis. METHODS: MRI scans of the dominant wrist were scored for synovitis, tendon inflammation, bone oedema, and erosion at first presentation (n = 42), at 1 year (n = 42), and at 6 years (n = 31). At 8 years, clinical reassessment (n = 28) was undertaken. Tendon function was graded 0-3 for movement, tendon sheath swelling, and pain on resistance at nine flexor and extensor tendons of the hand. Hand function was also assessed using the Sollerman grip test. The requirement for joint or tendon surgery by 8 years was determined by telephone survey in 39 of the original 42 patients. RESULTS: At 8 years, tendon function was highly correlated with hand function (Sollerman score, R = -0.51, p = 0.005) and global function (health assessment questionnaire score, R = 0.53, p = 0.004). Using a model incorporating baseline and 1 year MRI scores, the MRI bone oedema score was strongly predictive of tendon function at 8 years (chi(2)(2) = 15.3, p = 0.0005), as was the MRI bone erosion score (chi(2)(2) = 9.23, p = 0.01). Hand function was also predicted by the baseline MRI erosion score (p = 0.02). MRI variables did not predict the requirement for surgery, but patients who had surgery were more likely to show progression of MRI bone erosion scores between baseline and 1 year (p = 0.008). CONCLUSIONS: Extensive MRI bone oedema and erosions at the wrist in early rheumatoid arthritis predict tendon dysfunction and impaired hand function in the medium term but not the requirement for joint or tendon surgery.

McQueen F, Beckley V, Crabbe J, Robinson E, Yeoman S, Stewart N. · University of Auckland and Auckland District Health Board, Auckland, New Zealand. <> · Arthritis Rheum. · Pubmed #15751075 links to  free full text

Abstract: OBJECTIVE: To determine whether magnetic resonance imaging (MRI) evidence of tendinopathy in early rheumatoid arthritis (RA) could be used to predict the course of tendon involvement in later disease and specifically the risk of tendon rupture. METHODS: The occurrence, pattern, and progression of tendinopathy were studied prospectively over 6 years in a cohort of patients who had presented with RA. Of 42 patients enrolled, full MRI and clinical data were available for 31 at 6 years. MRI scans of the dominant wrist were scored for tendinopathy by 2 radiologists using a validated system. These data were compared with MRI synovitis, erosion scores, and disease activity measures. Prognostic factors for tendon inflammation and rupture were sought. RESULTS: Thirty-four patients (81%) had MRI evidence of tendinopathy at baseline, falling to 59% at 1 year and 68% at 6 years. The most commonly affected site was the extensor carpi ulnaris. MRI tendinopathy and synovitis scores were correlated at baseline (r = 0.37, P = 0.01) and 1 year (r = 0.45, P = 0.003) but not at 6 years (r = 0.11, P = 0.5). The strongest predictor of the 6-year tendinopathy score was the 1-year tendinopathy score (R(2) = 0.36, P = 0.0003 [beta = 1.28, SE = 0.31]). In 4 patients, extensor tendon rupture had occurred by 6 years. Their baseline and 1-year tendinopathy scores were higher than in the nonrupture group (medians 2.8 versus 1.0 [P = 0.04] and 4.3 versus 0.8 [P = 0.03], respectively), as were their Health Assessment Questionnaire scores (1.33 versus 0.54 [P = 0.02], 1.18 versus 0.25 [P = 0.03], and 0.98 versus 0.37 [P = 0.01] at 0, 1, and 6 years, respectively). For the group as a whole, the baseline tendinopathy score was predictive of rupture at 6 years (odds ratio [OR] 1.52, 95% confidence interval [95% CI] 1.02-2.32, P = 0.03), as was the 1-year score (OR 1.57, 95% CI 1.03-2.04, P = 0.02). CONCLUSION: MRI can be used to quantify tendinopathy at the wrist in RA patients. High scores in early disease were predictive of tendon rupture in a small group of patients, but further studies are required to determine whether this has clinical relevance.

Perry D, Stewart N, Benton N, Robinson E, Yeoman S, Crabbe J, McQueen F. · Departments of Rheumatology and Radiology, Auckland District Health Board, Auckland University, Auckland, New Zealand. · J Rheumatol. · Pubmed #15693085 No free full text.

Abstract: OBJECTIVE: To compare the detection and scoring of erosions in patients with rheumatoid arthritis (RA) using magnetic resonance (MR) and multidetector helical computerized tomographic (CT) scanning. METHODS: Comparative CT and MR scans of the dominant wrist were obtained from 9 patients with RA and clinical examination was performed to assess disease activity. MR and CT scans were scored for erosions and MR scans for bone edema by 2 radiologists using a validated system. Radiographs of the hands and feet were also scored for erosions using the modified Sharp score. RESULTS: In 117 of 135 (87%) sites there was concordance for erosions between MR and CT scans. At the remaining 18/135 sites (13%), erosions were identified by CT but not MR in 12/135 (9%) and by MR but not CT in 6/135 (4%). Partial volume artefacts on MR images and shifts in slice position were the most common reasons for erosion mismatch between MR and CT. The mean CT bone erosion score was significantly higher than the MR erosion score when individual bony sites were examined (p = 0.024), with the greatest difference being at the metacarpal bases. The total bone erosion score also tended to be higher on CT than MR [median scores of 20 (range 0-66) and 12 (0-51), respectively; p = 0.060]. MR and CT erosion scores correlated strongly with the total Sharp score (r = 0.93, p = 0.0002 and r = 0.94, p = 0.0002, respectively) and with the Disease Activity Score (MR: r = 0.77, p = 0.02; CT: r = 0.71, p = 0.03). CONCLUSION: Most erosions were detected using both modalities, but erosion scores were higher on CT than MR scans, especially at the metacarpal bases. It is possible that small erosions in some regions are more easily detected by CT because of its ability to clearly delineate cortical bony margins.

Benton N, Stewart N, Crabbe J, Robinson E, Yeoman S, McQueen FM. · Department of Rheumatology, Auckland Hospital, Aukland, New Zealand. · Ann Rheum Dis. · Pubmed #15082487 links to  free full text

Abstract: OBJECTIVES: To determine whether magnetic resonance (MR) scans of the dominant wrist of patients with early rheumatoid arthritis (RA) can be used to predict functional outcome at 6 years' follow up. METHODS: Dominant wrist MR scans were obtained in 42 patients with criteria for RA at first presentation. Patients were followed up prospectively for 6 years, and further scans obtained at 1 year (42 patients) and 6 years (31 patients). Two radiologists scored scans for synovitis, tendonitis, bone oedema, and erosions. The Stanford Health Assessment Questionnaire (HAQ) score, indicating functional outcome, and standard measures of disease activity were assessed at 0, 1, 2, and 6 years. The physical function component of the SF-36 score (PF-SF36) was also used as a functional outcome measure at 6 years. RESULTS: Baseline MR parameters, including bone oedema score and the total baseline MR score, were predictive of the PF-SF36 at 6 years (R2 = 0.22, p = 0.005 and R2 = 0.16, p = 0.02, respectively). The PF-SF36 score correlated strongly with the HAQ score at 6 years (rs = -0.725, p<0.0001); none of the baseline MR parameters predicted the 6 year HAQ score. The total MR score obtained at 1 year was predictive of the 6 year HAQ (R2 = 0.04, p = 0.01). Standard clinical and radiographic measures at baseline were not predictive of the 6 year PF-SF36, but when combined in a model with baseline MR oedema score, prediction increased from 0.09 to 0.23, or 23% of the 6 year variance. CONCLUSION: MR imaging of the wrist in patients with early RA can help to predict function at 6 years and could be used to plan aggressive management at an earlier stage.

McQueen FM, Benton N, Crabbe J, Robinson E, Yeoman S, McLean L, Stewart N. · Department of Molecular Medicine, Auckland School of Medicine, Auckland University, New Zealand. · Ann Rheum Dis. · Pubmed #11502613 links to  free full text

Abstract: OBJECTIVES: To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period. METHODS: Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of individual erosions over two years. RESULTS: The baseline MRI erosion score was predictive of x ray erosion score at two years (p=0.004). Patients with a "total MRI score" (erosion, bone oedema, synovitis, and tendonitis) > or =13 at baseline were significantly more likely to develop erosions on x ray at two years (odds ratio 13.4, 95% CI 2.65 to 60.5, p=0.002). Baseline wrist MRI has a sensitivity of 80%, a specificity of 76%, a positive predictive value of 67%, and a high negative predictive value of 86% for the prediction of wrist x ray erosions at two years. A lesion centred analysis, which included erosions scored by one or both radiologists, showed that 84% of baseline MRI erosions were still present at one year. When a more stringent analysis was used which required complete concordance between radiologists, all baseline lesions persisted at one year. The number of MRI erosion sites in each patient increased from 2.1 (SD 2.7) to 5.0 (4.6) (p<0.0001) over the first year of disease. When MRI erosion sites were tracked, 21% and 26% were observed on x ray, one and two years later. A high baseline MRI synovitis score, Ritchie score, and erythrocyte sedimentation rate were predictive of progression of MRI erosions to x ray erosions over one year (p=0.005, 0.01, and 0.03 respectively), but there was no association with the shared epitope. Progression of MRI erosions to x ray erosions was not seen in those with transient polyarthritis. CONCLUSIONS: MRI scans of the wrist, taken when patients first present with RA, can predict radiographic erosions at two years. MRI may have a role in the assessment of disease prognosis and selection of patients for more or less aggressive treatment. However, only one in four MRI erosions progresses to an x ray erosion over one year, possibly owing to healing, observer error, or technical limitations of radiography at the carpus. Progression of MRI erosions to x ray erosions is greatest in those with high baseline disease activity.

Huang J, Stewart N, Crabbe J, Robinson E, McLean L, Yeoman S, Tan PL, McQueen FM. · Department of Rheumatology, Auckland Hospital, Private Bag 92024, Auckland 1, New Zealand. · Rheumatology (Oxford). · Pubmed #10817774 links to  free full text

Abstract: OBJECTIVES: Dynamic magnetic resonance imaging (MRI) allows visualization of the synovial membrane and measurement of synovitis within the joint. A cohort of patients with early rheumatoid arthritis (RA) were studied using MRI of the dominant wrist and clinical assessments. Associations between synovitis and the shared epitope genotype (SE) were looked for and synovitis as a predictor of joint erosion was examined. METHODS: Gadolinium-enhanced MRI scans of the dominant wrist were performed in 42 early RA patients at baseline (median disease duration = 4 months) and after 1 yr. Images were obtained at 42-s intervals over the first 6 min after gadolinium-diethylenetriamine pentaacetic acid injection using six cuts in the coronal plane, 2 mm apart. The site of maximal synovial enhancement was selected as the region of interest (ROI). The rate of enhancement (E-rate) was calculated and compared with synovitis scores from static MRI scans, clinical disease activity scores and HLA-DRB1*04/01 genotyping [sequence-specific primer polymerase chain reaction (SSP-PCR) and DNA sequencing]. RESULTS: Reproducibility of the E-rate measurement was assessed by re-evaluating 10 randomly selected scans in a blinded fashion. Intra-observer reliability was high with an intraclass correlation coefficient of 0.91, 95% confidence interval (CI) 0.65-0.97. The E-rate correlated strongly at baseline with the maximum level of synovial enhancement (E-max) (r = 0.88, P < 0.0001) and the static MRI synovitis score (r = 0.52, P = 0.0004). There was also a weaker but significant correlation between E-rate and the pain score (r = 0.29, P = 0.04). The E-rate fell from baseline to 1 yr (P = 0.02) concordant with clinical improvement after treatment with standard therapies. E-rate scores were higher in SE+ than SE - patients (F(1,25) = 5.19, P = 0.03) and were predictive of MRI erosions at 1 yr [chi-square = 5.0 (1 d.f.), P = 0.03]. The baseline C-reactive protein (CRP) was also predictive of MRI erosions at 1 yr to a similar degree [chi-square = 4.7 (1 d.f. ), P = 0.03] but the mean static synovitis score at baseline was the strongest predictor [chi-square = 9.2 (1 d.f.), P = 0.003]. CONCLUSIONS: These results show that dynamic MRI can be used to score synovitis objectively in early RA patients. Synovitis was greater in SE+ patients, suggesting an early genetic influence on joint inflammation, and was predictive for the development of erosions at 1 yr.

McQueen FM, Stewart N, Crabbe J, Robinson E, Yeoman S, Tan PL, McLean L. · Department of Molecular Medicine, Auckland School of Medicine, Auckland University, New Zealand. · Ann Rheum Dis. · Pubmed #10364913 links to  free full text

Abstract: OBJECTIVES: To investigate the progression of joint damage in early rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of the wrist and determine whether this technique can be used to predict prognosis. METHODS: An inception cohort of 42 early patients has been followed up prospectively for one year. Gadolinium enhanced MRI scans of the dominant wrist were obtained at baseline and one year and scored for synovitis, tendonitis, bone marrow oedema, and erosions. Plain radiographs were performed concurrently and scored for erosions. Patients were assessed clinically for disease activity and HLA-DRB1 genotyping was performed. RESULTS: At one year, MRI erosions were found in 74% of patients (31 of 42) compared with 45% at baseline. Twelve patients (28.6%) had radiographic erosions at one year. The total MRI score and MRI erosion score increased significantly from baseline to one year despite falls in clinical measures of inflammation including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and swollen joint count (p < 0.01 for all). Baseline findings that predicted carpal MRI erosions at one year included a total MRI score of 6 or greater (sensitivity: 93.3%, specificity 81.8%, positive predictive value 93.3%, p = 0.000007), MRI bone oedema (OR = 6.47, p < 0.001), MRI synovitis (OR = 2.14, p = 0.003), and pain score (p = 0.01). Radiological erosions at one year were predicted by a total MRI score at baseline of greater than 13 (OR = 12.4, p = 0.002), the presence of MRI erosions (OR = 11.6, p = 0.005), and the ESR (p = 0.02). If MRI erosions were absent at baseline and the total MRI score was low, radiological erosions were highly unlikely to develop by one year (negative predictive value 0.91 and 0.92 respectively). No association was found between the shared epitope and erosions on MRI (p = 0.4) or radiography (p = 1.0) at one year. CONCLUSIONS: MRI scans of the dominant wrist are useful in predicting MRI and radiological erosions in early RA and may indicate the patients that should be managed aggressively. Discordance has been demonstrated between clinical improvement and progression of MRI erosion scores.

McQueen F, Robinson E. · No affiliation provided · Arthritis Rheum. · Pubmed #15529382 links to  free full text

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