Richard J. Wakefield

Guidelines for musculoskeletal ultrasound in rheumatology

Within the past decade, musculoskeletal ultrasound (US) has become an established imaging technique for the diagnosis and follow up of patients with rheumatic diseases.1-5 This has been made possible through technological improvements, resulting in faster computers and higher frequency transducers. US is most commonly used in the assessment of soft tissue disease or detection of fluid collection and can also be used to visualise other structures, such as cartilage and bone surfaces.6 7 Owing to the better axial and lateral resolution of US, even minute bone surface abnormalities may be depicted. Thus destructive and/or reparative/hypertrophic changes on the bone surface may be seen before they are apparent on plain x rays or even magnetic resonance imaging.8 However, US wave frequencies cannot penetrate into bone, therefore imaging of intra-articular disease is usually not possible. The “real time” capability of US allows dynamic assessment of joint and tendon movements, which can often aid the detection of structural abnormalities. Advantages of US include its non-invasiveness, portability, relative inexpensiveness, lack of ionising radiation, and its ability to be repeated as often as necessary, making it particularly useful for the monitoring of treatment. US can also be used for guidance of aspiration, biopsy, and injection treatment.9 Most musculoskeletal work is performed using “grey scale”, which means images are produced in a black and white format; each white dot in the image represents a reflected sound wave. Sound waves travel in a similar way to light waves and therefore the denser a material is—for example, bone cortex, the more reflective it is and the whiter it appears on the screen. Water is the least reflective body material and therefore appears as black as the sound waves travel straight through it. Newer US techniques, which are currently being evaluated, include colour and power …

An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis

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.

2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

The objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.

THE RELATIONSHIP BETWEEN SYNOVITIS AND BONE CHANGES IN EARLY UNTREATED RHEUMATOID ARTHRITIS A Controlled Magnetic Resonance Imaging Study

OBJECTIVE The interrelationship between synovitis and bone damage in rheumatoid arthritis (RA) is a subject of controversy. Using magnetic resonance imaging (MRI), this study followed the bone changes in early RA and determined their relationship to synovitis. METHODS Thirty-one patients with early RA who had swelling of the metacarpophalangeal (MCP) joints and 31 healthy control subjects with no clinical evidence of arthritis underwent MRI of the second through fifth MCP joints of the dominant hand by use of a 1.5T scanner. Coronal T1-weighted and T2-fat suppressed (FS) sequences were performed to evaluate bone edema, and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) pulse sequences were obtained to evaluate synovitis. Bony abnormalities were described as bone edema (low signal on T1-weighted sequences and intermediate/high signal on T2 FS sequences adjacent to the bone cortex) or as bone cysts (circular juxtacortical abnormalities with low signal on T1-weighted images and with very high signal on T2 FS sequences). Contrast and noncontrast MRI films were scored in a blinded manner, and Fishers exact probability test was used to determine differences between groups. RESULTS Twenty-one of the 31 RA patients (68%) had bone edema, which was seen in 43 of 124 joints (35% of joints) and 3 of the 31 control subjects had bone edema seen in 3 of 124 joints (2% of joints) (P < 0.0001). Thirty RA patients (97%) had Gd-DTPA-confirmed MCP joint synovitis, and bone edema was seen in 40 of the 75 joints with Gd-DTPA-proven synovitis (53%), but in only 3 of 49 without (6%) (P < 0.0001). CONCLUSION MCP joint bone edema is present in the majority of patients with RA at presentation, but is seen only occasionally in normal control subjects. The fact that bone edema occurred rarely in the absence of synovitis in patients with RA suggests that bony changes in RA are secondary to synovitis.

Interobserver reliability of rheumatologists performing musculoskeletal ultrasonography: results from a EULAR “Train the trainers” course

Objective: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging “gold standard”. Methods: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. Results: Taking an agreement in US examination of 10 out of 14 experts into account, the overall κ for all examined joints was 0.76. Calculations for each joint region showed high κ values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). κ Values for bone lesions, bursitis, and tendon tears were high (κ = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). Conclusion: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: Prevalence of inflammation in osteoarthritis

Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. Methods: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity ⩾30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness ⩾4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth ⩾4 mm. Results: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade ⩾3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory “flare”, such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). Conclusion: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory “flare”.

Interobserver reliability in musculoskeletal ultrasonography: results from a “Teach the Teachers” rheumatologist course

Objective: To assess the interobserver reliability of the main periarticular and intra-articular ultrasonographic pathologies and to establish the principal disagreements on scanning technique and diagnostic criteria between a group of experts in musculoskeletal ultrasonography. Methods: The shoulder, wrist/hand, ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23 musculoskeletal ultrasound experts from different European countries randomly assigned to six groups. The participants did not reach consensus on scanning method or diagnostic criteria before the investigation. They were unaware of the patients’ clinical and imaging data. The experts from each group undertook a blinded ultrasound examination of the four anatomical regions. The ultrasound investigation included the presence/absence of joint effusion/synovitis, bony cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler signal. Afterwards they compared the ultrasound findings and re-examined the patients together while discussing their results. Results: Overall agreements were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power Doppler signal; κ values were good for the wrist/hand and knee (0.61 and 0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal differences in scanning method and diagnostic criteria between experts were related to dynamic examination, definition of tendon lesions, and pathological v physiological fluid within joints, tendon sheaths, and bursae. Conclusions: Musculoskeletal ultrasound has a moderate to good interobserver reliability. Further consensus on standardisation of scanning technique and diagnostic criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor, and the shared epitope.

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

The impact of ultrasonography on diagnosis and management of patients with musculoskeletal conditions

There is increasing interest in the use of ultrasonography (US) in rheumatology (1). Ultrasonography is noninvasive, safe (uses no ionizing radiation), and can be used repeatedly in an outpatient setting which provides immediate access for patients. Availability of US varies widely between hospitals, with most of the referrals being for specific conditions such as rotator cuff tears. This usually requires a separate visit to the radiology department and then a return visit to the referring physician. There is accumulating evidence that US is more accurate than clinical examination in the detection of synovitis and tenosynovitis in small joints (2,3), and its use in musculoskeletal conditions is becoming increasingly validated (4). There is, however, a paucity of data assessing its actual impact on patient management. This study evaluated the diagnostic and therapeutic impact of musculoskeletal US in rheumatology outpatient clinics. Of 520 consecutive rheumatology outpatients seen, 100 were referred for US, and were enrolled in the study following provision of informed consent. All patients underwent a routine assessment, including a detailed history and clinical examination by experienced physicians. The indication for US, the site of interest, and site-specific diagnosis (SSD; e.g., synovitis, tenosynovitis), which was diagnosed clinically by the attending physician, were documented. The overall diagnosis (OD; e.g., rheumatoid arthritis, gout) and management plan were also recorded. Patients had US performed during the same clinic visit (on the requested sites only) by a rheumatology research fellow experienced in US, using an on-site ATL HDI 3000 machine (Advanced Technology Laboratories, Bothel, Washington). A linear array 10-5 MHz “hockey stick” transducer was used to examine most joints and a curvilinear array 5-3 MHz transducer was used to examine the hip. The referring physician subsequently reviewed the US report for each patient in the same clinic, and any change in the diagnosis or management as a result of US was documented. Of the 100 patients referred for US, 73 were female and the mean age was 50 years (range 17–87 years). Sixty-four patients were referred to confirm a diagnosis alone, while 36 were referred for diagnosis and local corticosteroid injection. Twenty of these 36 patients (56%) had reported a poor response to a previous “blind” corticosteroid injection. A total of 121 sites were examined by US (Table 1). US was requested to confirm the presence or absence of synovitis in 86 of the 121 sites (71%), enthesitis in 11 of 121 sites (9%), and tenosynovitis in 9 of 121 sites (7%). Following review of the US findings, the SSD was changed in 53 of 100 patients (53%) and 60 of 121 sites (50%). In order of frequency, the changes in clinical SSD were synovitis in 43 of 60 sites (72%), tenosynovitis in 7 of 60 sites (12%), and enthesitis in 5 of 60 sites (8%). The frequency of SSD change, by site, is listed in Table 1. The OD was changed in 5 of 100 patients (5%). There were a further 8 of 100 patients (8%) in whom US helped confirm a provisional OD. The management plan was altered in 53 of 100 patients (53%) after US, of which 39 were due to a change in SSD and 14 were a result of US confirming a provisional SSD. The corticosteroid regimen was affected in 43 patients. Planned intraarticular corticosteroid injections were altered in 22 patients, and in 14 patients, a new injection was given after US. Parenteral corticosteroid therapy was affected in 7 patients. Only 14 (39%) of the 36 intended injections were given at the planned intraarticular site. Disease-modifying antirheumatic drug (DMARD) therapy was affected in 13 patients, of which 10 were due to the detection of extensive subclinical synovitis. This study suggests that US has a diagnostic and therapeutic impact in the majority of referred patients who attend rheumatology clinics. When these findings are applied in the context of all patients attending clinics during the study period, US has an impact on diagnosis and management in at least 10% (53 of 520) of all cases. Consistent with previous reports, this study demonstrates a poor correlation between US and clinical examination in the detection of synovitis; the changes to DMARD therapy were mainly a result of detection of subclinical synovitis by US. This would suggest patients with clinically stable disease are often undertreated, and may help explain the continued bone damage reported in this group of patients (5). Response to corticosteroid injections is known to vary considerably, and there is evidence that accurately placed injections result in improved patient outcome (6,7). Interestingly, as a consequence of US, less than half the referred patients received an injection at the preplanned site. The impact of US on corticosteroid injections therefore reflects the limitations of clinical assessment in accurately localizing pathologic sites and may explain, in part, the variation in response to conventionally placed injections. This study also documents the referral pattern when rheumatologists have direct access to US, with most patients referred for assessment of small-joint synovitis and guided injections. After initial capital expenditure, the only running costs Table 1. Sites examined by ultrasonography, with frequency of change in site-specific diagnosis (SSD)

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.