P O'Connor

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)

Histological assessment of the early enthesitis lesion in spondyloarthropathy

Objectives: To describe the histological changes in acute enthesopathy in early spondyloarthropathies (SpA). Methods: Clinically evident acute enthesopathy was confirmed by magnetic resonance imaging and ultrasonography in four cases of plantar fasciitis and one case of patellar tendon enthesitis. Ultrasound guided biopsy of insertional points was carried out with a Jamshedi needle. Control tissue was obtained from two subjects undergoing spinal grafting surgery. Standard histochemistry and immunohistochemistry analysis using the avidin-biotin immunoperoxidase complex method employing markers against CD3, CD8, CD34, and CD68 was used to determine cellular infiltrates at the insertion point. Results: The enthesis architecture was abnormal in the SpA group, with increased vascularity and cellular infiltration compared with normal subjects. The predominant infiltrating cell at the enthesis fibrocartilage was the macrophage, but there was a paucity of lymphocytes at the insertion point. Conclusion: These preliminary findings have implications for a better understanding of the pathology in early SpA.

The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint

This paper presents the wrist joint MR images of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0–3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system—that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0–3 of bone oedema are illustrated, and for bone erosion, grades 0–3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system.

The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI

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.

Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology

OBJECTIVES CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology. METHODS Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site. RESULTS 12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated. CONCLUSIONS SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.

Human immunodeficiency virus associated spondyloarthropathy: pathogenic insights based on imaging findings and response to highly active antiretroviral treatment

The pathogenesis of human immunodeficiency virus (HIV) associated spondyloarthropathy (SpA) is poorly understood. In this case report a patient is described with severe HIV associated reactive arthritis, who on magnetic resonance imaging and sonographic imaging of inflamed knees had extensive polyenthesitis and adjacent osteitis. The arthritis deteriorated despite conventional antirheumatic treatment, but improved dramatically after highly active antiretroviral treatment, which was accompanied by a significant rise in CD4 T lymphocyte counts. The implications of the localisation of pathology and effect of treatment for pathogenic models of SpA and rheumatoid arthritis in the setting of HIV infection are discussed.

Contrast-enhanced MRI of the subdeltoid, subacromial bursa in painful and painless rotator cuff tears

OBJECTIVE Although shoulder pain is often associated with rotator cuff tears, many tears are asymptomatic and are not the cause of the patients pain. This may explain the persistence of symptoms in some patients despite technically successful rotator cuff repair. It has been proposed that rotator cuff tears cause pain through subdeltoid/subacromial bursal inflammation. The aim of this study was to determine whether bursal inflammation seen on MRI is associated with pain in patients with rotator cuff tears of the shoulder. METHODS The shoulders of 255 patients were screened with ultrasound. 33 full-thickness rotator cuff tears (18 with shoulder pain and 15 without pain) were identified and subsequently studied using contrast-enhanced MRI of the shoulder. Enhancement of the subacromial bursa was scored independently by two musculoskeletal radiologists. Logistic regression was used to determine whether bursal enhancement was independently associated with pain. RESULTS There was a significant association between pain and age, with greater likelihood of pain in younger patients. Bursal enhancement was common in both painful and painless tears. No statistically significant link between pain and bursal enhancement was seen, even after accounting for age. CONCLUSION Although enhancement of the subdeltoid/subacromial bursa was common, no evidence was found to support the hypothesis that bursal enhancement is associated with pain in rotator cuff tears. It is therefore unlikely to determine reliably which patients would benefit from rotator cuff repair. Advances in knowledge Bursal enhancement and thickening does not reliably correlate with symptoms or presence of rotator cuff tear.

Subclinical vasculitis in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is an inflammatory condition of the aging population characterised by pain, stiffness, and symmetrical involvement of shoulder and pelvic girdles. It has been proposed that the primary site of disease may reside outside the synovial joint,1 2 but its aetiopathogenesis remains ill understood. There is good indirect evidence that vasculitis is important in the pathogenesis of PMR, based on observations from the closely related disease, giant cell arteritis (GCA).3 Many patients with GCA have PMR-like symptoms and the converse is also true. One of the characteristics of PMR is its dramatic response to moderate doses of corticosteroid treatment. However, a subset of patients responds inadequately to treatment or has difficulty with dose reduction, the basis for which is not well defined. We report here the case of a patient with PMR which was difficult to treat who was found to have underlying vasculitis on magnetic resonance imaging (MRI), a finding which explains the requirement for the …

Quantitative MRI measurements of the Achilles tendon in spondyloarthritis using ultrashort echo times.

OBJECTIVES Tendon involvement is common in spondyloarthritis. The MRI signal from the Achilles tendon has been used to quantify mechanical tendinopathy; however, conventional MRI is limited by the short T(2) of normal tendon. Short and ultrashort echo time (UTE) MRI have the potential to better measure signal intensity reflecting changes in T(2) or gadolinium enhancement. Furthermore, UTE images could be used for normalisation to reduce variability. The aim of this work was to investigate such techniques in patients with spondyloarthritis (SpA). METHODS The Achilles tendons of 14 healthy volunteers and 24 patients with symptomatic spondyloarthritis were studied. Combined UTE (TE=0.07 ms) and gradient echo (TE=4.9 ms) images were acquired before and after intravenous gadolinium together with pre-contrast gradient echo images (TE=2 ms). The signal intensity from a region of interest in the Achilles tendon above the calcaneus was measured. The relative enhancement at echo times of 0.07 ms (RE(0.1)) and 4.9 ms (RE(5)) were calculated. The ratios of the signal intensities from both 4.9 ms and 2 ms gradient echo images to the signal intensity from the UTE image were calculated (RTE(5) and RTE(2) respectively). RESULTS Interobserver intraclass correlation coefficients were excellent (≥0.97). The contrast-to-noise ratio was higher for enhancement on UTE images than on gradient echo images. RE(0.1), RTE(5) and RTE(2) were significantly higher in SpA patients than controls. CONCLUSION Signal intensity ratios using UTE images allow quantitative measurements to be made which are sensitive to tendon T(2) or contrast enhancement and which are increased in spondyloarthritis. They therefore have the potential for use as measures of tendon disease in spondyloarthritis.