Recommendations for rheumatology ultrasound training and practice in the UK.

OBJECTIVE: The aim of this paper is to present a UK-based consensus of principles and recommendations to guide rheumatology US training and practice. METHOD: A Delphi process was conducted involving 19 US experts representing each of the 14 regions of the UK. A working group of experienced British Society for Rheumatology Ultrasound Special Interest Group (BSRUSSIG) members made seven proposals that were presented to the whole group for further discussion. This resulted in minor modifications and seven preliminary recommendations. Members were then asked to anonymously agree or disagree with each recommendation using an electronic ballot. A threshold of 75% was used to determine consensus agreement. Results were collated by an independent chairperson and presented to the BSRUSSIG in a face to face meeting where agreement for each recommendation was ratified and an action plan agreed for dissemination of the results and future development work. RESULTS: Using a validated process, experts in rheumatology US have worked through an iterative process and have unanimously agreed seven recommendations for rheumatology training and practice. These cover a hierarchy of practice indications, education and training, including the need for practitioners to demonstrate lifelong learning, as well as a commitment to support mentors and trainers through the BSRUSSIG. CONCLUSION: These are the first specific education and practice recommendations for rheumatology US in the UK and have been developed and endorsed by the BSRUSSIG. We intend that these proposals will help to support and validate rheumatology US practice and inform the development of future rheumatology training curricula and education programmes.

OMERACT agreement and reliability study of ultrasonographic elementary lesions in osteoarthritis of the foot.

Objective: To evaluate the level of agreement on ultrasonographic (US) lesions among highly experienced sonographers as well as the intraobserver and interobserver reliability of inflammatory and structural US lesions in patients with osteoarthritis (OA) of the foot. Methods: After a systematic literature review, a Delphi survey was performed to test definitions of US lesions in OA of the foot, including inflammatory lesions (ie, synovial hypertrophy [SH], joint effusion [JE], power Doppler signal [PD]), and structural abnormalities (ie, cartilage damage [CD] and osteophytes). Subsequently, the reliability of US in assessing the aforementioned lesions was tested on static images as well as during a live exercise. Reliability was assessed by kappa analyses and prevalence-adjusted bias-adjusted kappa (PABAK) on a dichotomous and an ordinal scale. Results: Intraobserver and interobserver reliability for SH and JE evaluated by binary scoring was good for both components, while the intraobserver reliability for semiquantitative scoring of SH ranged from moderate in the web-based exercise (PABAK 0.49) to good (PABAK 0.8) in the live exercise. Reliability for CD and PD assessments were respectively good and excellent in all exercises (ranged from PABAK 0.61 to 0.79 for CD and 0.88 to 0.95 for PD). The interobserver reliability for the semiquantitative scoring of osteophytes was fair in the live exercise (PABAK 0.36) and moderate in the static exercise (PABAK 0.60). Conclusions: Consensual US definitions were found to be reliable for assessing inflammatory lesions in OA of the foot, while the use of US to assess structural damage requires further studies.

Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis.

OBJECTIVE: To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). METHODS: We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. RESULTS: Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). CONCLUSIONS: US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.

Reliability testing of tendon disease using two different scanning methods in patients with rheumatoid arthritis.

OBJECTIVE: To assess the intra- and interobserver reliability of musculoskeletal ultrasonography (US) in detecting inflammatory and destructive tendon abnormalities in patients with RA using two different scanning methods. METHODS: Thirteen observers examined nine patients with RA and one healthy individual in two rounds independently and blindly of each other. Each round consisted of two consecutive examinations, an anatomy-based examination and a free examination according to personal preferences. The following tendons were evaluated: wrist extensor compartments 2, 4 and 6, finger flexor tendons 3 and 4 at MCP level, tibialis posterior tendon and both peronei tendons. Overall, positive and negative agreements and κ-values for greyscale (GS) tenosynovitis, peritendinous power Doppler (PPD) signal, intratendinous power Doppler (IPD) signal and GS tendon damage were calculated. RESULTS: Intraobserver κ-value ranges were 0.53-0.55 (P < 0.0005) for GS tenosynovitis, 0.61-0.64 (P < 0.0005) for PPD signal, 0.65-0.66 (P < 0.0005) for IPD signal and 0.44-0.53 (P < 0.0005) for GS tendon damage. For interobserver reliability, substantial overall agreement ranged from 80 to 89% for GS tenosynovitis, 97 to 100% for PPD signal, 97 to 100% for IPD signal and 97 to 100% for GS tendon damage. Results were independent of scanning technique. CONCLUSION: Intraobserver reliability for tenosynovitis and tendon damage varied from moderate for GS to good for PD. Overall interobserver reliability for tenosynovitis and tendon damage was excellent both for GS and PD. This qualitative scoring system may serve as the first step to a semi-quantitative score for tendon pathology.

Can flare be predicted in DMARD treated RA patients in remission, and is it important? A cohort study.

OBJECTIVES: The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes. METHODS: RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy. RESULTS: 26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission. CONCLUSION: The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.

Should imaging be a component of rheumatoid arthritis remission criteria? A comparison between traditional and modified composite remission scores and imaging assessments.

OBJECTIVES: Patients can fulfil clinical criteria for remission, yet still have evidence of synovitis detectable clinically and by ultrasound, and this is associated with structural damage. Stricter remission criteria may more accurately reflect true remission (no synovitis). This hypothesis was examined by studying patients using more stringent thresholds for clinical remission and determining their levels of ultrasound synovitis. METHODS: Rheumatoid arthritis patients with a disease activity score in 28 joints (DAS28) ≤2.6 for at least 6 months were classified using standard and more stringent DAS28 and simplified disease activity index (SDAI) remission thresholds and the corresponding clinical and ultrasound imaging measures of synovitis recorded. RESULTS: 128 patients (all DAS28 <2.6, median DAS28 1.70) receiving either disease-modifying antirheumatic drugs alone (n=66) or with a tumour necrosis factor blocker (n=62) were recruited. Of the 640 imaged joints, 5% had moderate or severe power Doppler (PD) activity, 8% were clinically swollen and 1% tender. In patients fulfilling DAS28, American College of Rheumatology or SDAI remission criteria, moderate or severe PD activity was present in 21%, 15% and 19%, respectively. More stringent DAS28 and SDAI criteria reduced the mean number of swollen and tender joints (p<0.001) but not the percentage of patients with PD activity: 32 patients had a DAS28 <1.17 but eight (25%) had significant PD activity. CONCLUSION: Using more stringent remission criteria resulted in reduced signs and symptoms of inflammation, but the percentage of joints with PD activity was not reduced, even in those without signs or symptoms. These data suggest that clinical criteria are sufficiently insensitive to detect low but clinically relevant levels of inflammation accurately.

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease-modifying antirheumatic drugs: A clinical and imaging comparative study.

OBJECTIVE: For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis. METHODS: One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n = 50) or DMARDs (n = 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1-5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity. RESULTS: In patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P = 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission. CONCLUSION: In RA patients with disease in remission, imaging-detected synovitis persists, with power Doppler activity seen in >or=48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging-detected synovitis.

Response to intramuscular methyl prednisolone in inflammatory hand pain: evidence for a targeted clinical, ultrasonographic and therapeutic approach.

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.

Recommendations for musculoskeletal ultrasonography by rheumatologists: setting global standards for best practice by expert consensus.

OBJECTIVE: To establish an expert consensus of best practice for rheumatologists performing musculoskeletal ultrasonography (MUS). METHODS: A panel of worldwide experts in MUS was identified by literature review, membership of teaching faculty, and peer recommendation. They were invited to take part in a 4-stage Delphi process employing 2 iterative rounds to establish a consensus of specific indications, anatomic areas, and knowledge and skills required by rheumatologists performing MUS. RESULTS: Experts in MUS were identified (n = 57; 37 radiologists, 20 rheumatologists). Successive rounds of this rigorous Delphi exercise enabled group consensus to be achieved in 30 of the proposed 37 categories comprising 8 of 13 indications (inflammatory arthritis, tendon pathology, effusion, bursitis, monitoring disease activity, monitoring disease progression, guided aspiration, and injection), 8 of 10 anatomic areas (hand, wrist, elbow, shoulder, hip, knee, ankle and heel, and forefoot), and 14 categories of knowledge and skills (physics, anatomy, pathology, equipment, clinical application and relevance, indications and limitations, artifact, machine function and operation, patient and probe position, planes and system of examination, image optimization, dynamic assessment, color Doppler, and power Doppler). CONCLUSION: We have produced the first expert-derived, interdisciplinary consensus of recommendations for rheumatologists performing MUS. This represents a significant advance that will not only direct future rheumatology MUS practice, but will facilitate informed educational development. This is an important step towards the introduction of a specific training curriculum and assessment process to ensure competent rheumatologist ultrasonographers.

Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

Practice, training, and assessment among experts performing musculoskeletal ultrasonography: toward the development of an international consensus of educational standards for ultrasonography for rheumatologists.

OBJECTIVE: To evaluate the training and practice of specialist practitioners in musculoskeletal ultrasonography (MUS) with the aim of developing an expert-derived consensus of educational standards for rheumatologists performing MUS. METHODS: A panel of worldwide experts in MUS was identified by literature review, consultation with members of training committees, and peer recommendation. Using a postal questionnaire, information was obtained about personal experience, current practice, training regimen, and participation in competency assessment. RESULTS: International experts in MUS were identified (57 in total: 37 radiologists, 20 rheumatologists). Response rate was 70%. Radiologists had been performing MUS for longer than rheumatologists. Both rheumatologists and radiologists conducted the same number of MUS sessions per week, although radiologists examined more patients. More radiologists performed MUS for muscle and ligament injury, nerve lesions, soft tissue masses, and of the groin (P <0.01). The number of training hours was similar. Approaches to training varied, although attending a training course and scanning with an expert was more common among rheumatologists (P <0.001). More than two-thirds of the group had not undergone any form of competency assessment. CONCLUSION: This study highlights differences in training and practice between individual expert ultrasonographers and between specialty backgrounds. In particular, there appears to be no formal training regimen and competency assessment is uncommon. The establishment of a core set of internationally applicable educational standards for MUS training for rheumatologists is required.

Can early diagnosis and management of costochondritis reduce acute chest pain admissions?

OBJECTIVE: We identified patients presenting with chest pain diagnosed as costochondritis by a consultant rheumatologist. The time taken to diagnosis was determined and the influence of diagnosis on subsequent management was assessed. We then estimated any cost benefits that early diagnosis and treatment of costochondritis might confer. Finally, we evaluated our current experience of sulfasalazine as a treatment for recurrent costochondritis. METHODS: This was a retrospective observational study of 25 consecutive patients (17 female), mean age 50 years (range 26-75), with costochondritis who initially presented with acute chest pain. RESULTS: The mean time to diagnosis was 9.4 (0-57) months. The total number of chest pain admissions pre-review was 39 compared with 6 post-review (p < 0.0001). The number of minor investigations was 169 pre-review compared with 17 post-review (p < 0.0001), and major investigations 30 compared with 0 (p < 0.01). All 13 patients treated with corticosteroid injections reported symptomatic improvement, and 10 of the 11 whose symptoms recurred responded to sulfasalazine. CONCLUSION: Patients with costochondritis frequently present with acute chest pain, often resulting in multiple admissions and investigations. In this study admission and investigation rates were significantly reduced following rheumatological review. How much of this reduction is directly a result of rheumatological intervention is unclear, given the limitations of the study. The findings suggest early review may improve patient care and reduce expenditure; in recurrent cases of costochondritis, sulfasalazine may be of additional longterm benefit.

Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol.

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.

Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis.

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.