Rheumatoid Arthritis: Naredo E

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.

Naredo E, Möller I, Cruz A, Carmona L, Garrido J. · Hospital Severo Ochoa, Madrid, Spain. <> · Arthritis Rheum. · Pubmed #18668537 links to  free full text

Abstract: OBJECTIVE: To evaluate the validity, responsiveness, and predictive value of power Doppler ultrasonography (PDUS) monitoring of response to tumor necrosis factor (TNF) blocking agents in rheumatoid arthritis (RA). METHODS: Three hundred sixty-seven RA patients were prospectively recruited at 25 Spanish centers; complete clinical, laboratory, and PDUS data were obtained on 278 patients. The patients underwent clinical, laboratory, and PDUS assessment at baseline and after 1, 3, 6, and 12 months of anti-TNF treatment, and radiographic assessment of the hands and feet at baseline and 12 months. The Disease Activity Score in 28 joints (DAS28) was recorded at each visit. PDUS examination included 86 intraarticular and periarticular sites in 28 joints. US synovial fluid (SF), synovial hypertrophy (SH), and PD signal were scored in all synovial sites. US count and index for SF, SH, and PD signal were obtained. Sensitivity to change of the PDUS variables was assessed by estimating the smallest detectable difference (SDD) from the intraobserver variability. RESULTS: A significant parallel improvement in DAS28 and PDUS parameters was found at followup assessment (P < 0.0005 for within-subject between-visit changes). The SDD for PDUS parameters was lower than the mean changes throughout followup. Time-integrated values of US joint count for PD signal and rheumatoid factor (RF) showed predictive value in relation to progression of radiographic erosion (R = 0.64), and time-integrated values of US joint count for PD signal, RF, and erythrocyte sedimentation rate were predictors of progression of the total radiographic score (R = 0.59). CONCLUSION: These findings indicate that PDUS is a valid method for monitoring response to anti-TNF therapy in RA; results obtained by PDUS are reproducible and sensitive to change. PDUS findings may have predictive value in relation to radiologic outcome.

Naredo E, Collado P, Cruz A, Palop MJ, Cabero F, Richi P, Carmona L, Crespo M. · Hospital Severo Ochoa, Madrid, Spain. · Arthritis Rheum. · Pubmed #17266071 links to  free full text

Abstract: OBJECTIVE: To evaluate the sensitivity to change of power Doppler ultrasound (PDUS) assessment of joint inflammation and the predictive value of PDUS parameters in disease activity and radiologic outcome in patients with early rheumatoid arthritis (RA). METHODS: Forty-two patients with early RA who started therapy with disease-modifying antirheumatic drugs underwent blinded sequential clinical, laboratory, and ultrasound assessment at baseline, 3 months, 6 months, and 1 year and radiographic assessment at baseline and 1 year. For each patient, 28-joint Disease Activity Score (DAS28) was recorded at each visit. The presence of synovitis was investigated in 28 joints using gray-scale ultrasonography and intraarticular power Doppler signal. Active synovitis was defined as intraarticular synovitis detected with power Doppler signal. The ultrasound joint count for active synovitis and an overall joint index for power Doppler signal were calculated. Sensitivity to change of PDUS variables was assessed by estimating the smallest detectable difference (SDD) from the intraobserver variability. RESULTS: The SDD for ultrasound joint count for active synovitis and ultrasound joint index for power Doppler signal was lower than mean changes from baseline to 3 months, 6 months, and 1 year. Time-integrated values of PDUS parameters demonstrated a highly significant correlation with DAS28 after 1 year (r = 0.63, P < 0.001) and a stronger correlation with radiographic progression (r = 0.59-0.66, P < 0.001) than clinical and laboratory parameters (r < 0.5). CONCLUSION: PDUS is a sensitive and reliable method for longitudinal assessment of inflammatory activity in early RA. PDUS findings may have a predictive value in disease activity and radiographic outcome.

Naredo E, Gamero F, Bonilla G, Uson J, Carmona L, Laffon A. · Department of Rheumatology and Research Unit, Hospital de la Princesa, Madrid, Spain. · Clin Exp Rheumatol. · Pubmed #16396709 No free full text.

Abstract: OBJECTIVE: To investigate the validity of reduced joint counts for ultrasonographic (US) assessment of joint inflammatory activity in patients with rheumatoid arthritis (RA). METHODS: Ninety-four patients with RA were included. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were recorded for each patient. The presence of tenderness, swelling and a subjective swelling score from 0 to 3 were assessed by two rheumatologists who reached consensus in 60 joints examined in each patient. All patients underwent an US examination by a third blinded rheumatologist, using power Doppler (PD). US joint effusion, synovitis and PD signal were graded from 0 to 3 in the 60 joints. A 60-joint count and index for effusion, synovitis and PD signal were recorded. A 6-, 10-, 16-, 18-, and two 12-joint counts and indices for US parameters that included the most frequently US involved joints were calculated for each patient. RESULTS: A 12-joint assessment for effusion, synovitis and PD signal, including bilateral wrist, second and third MCP, second and third PIP of hands and knee joints highly correlated with corresponding 60-joint US counts and indices. This reduced-joint US evaluation showed a similar correlation with clinical and laboratory parameters of disease activity to corresponding 60-joint assessment. CONCLUSION: We propose that a 12-joint evaluation may be a useful tool for US assessment of overall joint inflammatory activity in RA.

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.

Naredo E, Rodríguez M, Campos C, Rodríguez-Heredia JM, Medina JA, Giner E, Martínez O, Toyos FJ, Ruíz T, Ros I, Pujol M, Miquel X, García L, Aznar JJ, Chamizo E, Páez M, Morales P, Rueda A, Tuneu R, Corominas H, de Agustín JJ, Moragues C, Mínguez D, Willisch A, González-Cruz I, Aragón A, Iglesias G, Armas C, Pablo Valdazo J, Vargas C, Calvo-Alén J, Juan-Mas A, Salvador G, Puigdollers A, Galíndez E, Garrido N, Salaberri J, Raya E, Salles M, Díaz C, Cuadra JL, Garrido J, Anonymous00163. · Hospital Severo Ochoa, Madrid, Spain. · Arthritis Rheum. · Pubmed #18383408 links to  free full text

Abstract: OBJECTIVE: To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. METHODS: A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. RESULTS: A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84-0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. CONCLUSION: A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.

Salaffi F, Filippucci E, Carotti M, Naredo E, Meenagh G, Ciapetti A, Savic V, Grassi W. · Department of Rheumatology, Università Politecnica delle Marche, Ancona, Italy. · Rheumatology (Oxford). · Pubmed #18037688 No free full text.

Abstract: OBJECTIVES: The aims of the present study were to assess the inter-observer agreement of standard joint count and to compare clinical examination with grey scale ultrasonography (US) findings in patients with early rheumatoid arthritis (RA). METHODS: The study was conducted on 44 RA patients with a disease duration of <2 yrs. Clinical evaluation was performed independently by two rheumatologists for detection of tenderness in 44 joints and swelling in 42 joints. All patients underwent US assessment by a rheumatologist experienced in this method and blinded to the clinical findings. Joint inflammation was detected by US when synovial fluid and/or synovial hypertrophy was identified using OMERACT preliminary definitions. The inter-observer reliability was calculated by overall agreement (percentage of observed exact agreement) and kappa (kappa)-statistics. The reliability of US was calculated in 12 RA patients. RESULTS: There was fair to moderate inter-observer agreement on individual joint counts for either tenderness or joint swelling apart from the glenohumeral joint. US detected a higher number of inflamed joints than did clinical examination. The mean (+/-S.D.) US joint count for joint inflammation was 19.1 (+/-4.1), while the mean (+/-S.D.) number of swollen joints was 12.6 (+/-3.6), with a significant difference of P = 0.01. CONCLUSIONS: Our results provide evidence in favour of the hypothesis that clinical examination is far from optimal for assessing joint inflammation in patients with early RA. Furthermore, this study suggests that US can considerably improve the detection of signs of joint inflammation both in terms of sensitivity and reliability.

Iagnocco A, Perella C, Naredo E, Meenagh G, Ceccarelli F, Tripodo E, Basili S, Valesini G. · Rheumatology Unit, University of Rome La Sapienza, Rome, Italy. · Clin Rheumatol. · Pubmed #17952483 No free full text.

Abstract: We evaluated clinically and sonographically the effects of etanercept therapy in patients with rheumatoid arthritis (RA) over 12 months of treatment. Eighteen patients affected by RA who were non-responders or partial responders to disease modifying therapy were commenced on Etanercept treatment. Before starting therapy (T0) and at 12 months (T1), the following parameters were evaluated: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS) for pain, number of painful and swollen joints, health assessment questionnaire (HAQ) and disease activity score in 28 joints (DAS 28). Musculoskeletal ultrasound (US) was performed in the following joints: second and fifth metacarpophalangeal, third interphalangeal, wrist and knee joints and a semiquantitative score (0-3) calculated and used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis, bursitis) and/or structural damage (bone erosion and cartilaginous change). An overall score was calculated based on the sum of the single scores to obtain a comprehensive score indicative of the global pathological change. The US global scores significantly reduced between T0 and T1 (p < 0.0001). The following laboratory and clinical parameters also significantly reduced: ESR (p < 0.0001), CRP (p < 0.02), VAS (p < 0.001), number of total swollen joints (p < 0.001), number of total painful joints (p < 0.01), HAQ scores (p < 0.05) and DAS 28 (p < 0.0001). A positive response to treatment with Etanercept was demonstrated both by US examination of several joints and by clinical evaluation of several parameters. US is a useful tool in the monitoring of biologic therapy in RA, assessing both inflammatory and destructive changes.

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.

Naredo E, Bonilla G, Gamero F, Uson J, Carmona L, Laffon A. · Department of Rhumatology, Hospital de la Princeca, Madrid, Spain. · Ann Rheum Dis. · Pubmed #15708891 links to  free full text

Abstract: OBJECTIVE: To compare the clinical assessment of overall inflammatory activity in patients with rheumatoid arthritis (RA) with grey scale and power Doppler (PD) ultrasonography (US). METHODS: Ninety four consecutive patients with RA were included. Demographic and clinical data, C reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were recorded for each patient. The presence of tenderness, swelling, and a subjective swelling score from 1 to 3 were independently assessed by two rheumatologists, who reached a consensus in 60 joints examined in each patient. All patients underwent a US examination by a third blinded rheumatologist, using PD. US joint effusion, synovitis, and PD signal were graded from 1 to 3 in the 60 joints. Joint count and joint index for effusion, synovitis, and PD signal were recorded. A 28 joint count for clinical and US variables was calculated. Interobserver reliability of the US examination was evaluated by a fourth blinded rheumatologist. RESULTS: US showed significantly more joints with effusion (mean 15.2) and synovitis (mean 14.6) than clinical examination (mean 11.5, p<0.05). A significant correlation was found between joint count and joint index for swelling, US effusion, synovitis, and PD signal. The 28 joint count for effusion, synovitis, and PD signal correlated highly with the corresponding 60 joint counts. US findings correlated better with CRP and ESR than clinical measures. Interobserver reliability was better for US findings than for clinical assessment. CONCLUSION: US is a sensitive method for assessing joint inflammatory activity in RA, complementary to clinical evaluation.

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

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