Wayne Gibbon

Classification of inflammatory arthritis by enthesitis

Imaging studies of early synovitis suggest that the first abnormality to appear in swollen joints associated with spondyloarthropathy is an enthesitis (inflammation at sites where ligaments, tendons, or joint capsules are attached to bone). We propose that the synovitis of spondyloarthropathy is secondary to liberation of proinflammatory mediators from the enthesis, whereas the synovitis of rheumatoid arthritis is primary. This suggestion allows a classification of arthritis as either primary synovial (rheumatoid-like) or entheseal (spondyloarthropathy-like) and allows differentiation of presentation of a polyarthritis with a good prognosis (spondyloarthropathy-like), from that with a bad prognosis (rheumatoid arthritis). Pathogenesis of spondyloarthropathy, in particular the part played by HLA-B27 and micro-organisms, should be assessed at the enthesis rather than in the synovium.

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.

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.

Enthesitis in spondyloarthropathy.

Inflammation at the insertions of ligaments, tendons, or joint capsules to bone, which is termed enthesitis, is a characteristic feature of spondyloarthropathy. Because of the relative inaccessibility of the enthesis, the inflammatory, microbiologic, and immunologic events at that site have been poorly defined. Recent magnetic resonance imaging studies have drawn attention to the ubiquitous nature of enthesitis in spondyloarthropathies, especially adjacent to synovial joints. This may have implications for the mechanisms of synovitis in spondyloarthropathies. Magnetic resonance imaging studies also suggest that enthesitis lesions may be extensive, which could explain the diffuse nature of bone changes seen in some patients with spondyloarthropathies. The importance of enthesitis as a skeletal phenomenon in spondyloarthropathies has gained further support from transgenic models in which either tumor necrosis factor-alpha or bone morphogenetic protein-6 overexpression result in entheseal-associated polyarthropathy.

ULTRASOUND IN INFLAMMATORY DISEASE

US may be used effectively to diagnose and treat a wide range of musculoskeletal inflammatory conditions. It is likely that its usage will increase with regards to such conditions especially in the management of rheumatology clinic patients.

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.

An anatomical explanation for good-prognosis rheumatoid arthritis

Although most patients with rheumatoid arthritis (RA) have persistent progressive disease there is a heterogeneity of outcome in early disease. An acute presentation of disease is one of the best predictors of a good outcome. On the basis of magnetic resonance imaging (MRI) studies, it has been suggested that there are two types of inflammatory joint disease, one with an intrasynovial location with a poor prognosis and one with an extrasynovial location which generally has a good prognosis. We wondered whether the good prognosis subset of RA was due to a different primary location of pathology. Untreated patients with RA were selected at presentation to the early arthritis clinic to represent the extremes of acute onset good-prognosis RA (GPRA) or insidious onset poor-prognosis RA (PPRA). 30 patients who fulfilled the American College of Rheumatology criteria for RA and 30 controls were studied by imaging; the latter group did not receive gaddiniumdiethylenetriamine penta-acetic acid contrast. RA patients were selected on the basis of their clinical presentation—22 patients with PPRA and eight patients with GPRA (onset of 24 h). MRI was done with a 1·5 T Gyroscan ACS NT (Philips Medical Systems) within 1 week of presentation to the clinic (table) with image acquisition by a surface coil. The clinicians responsible for patients’ care were unaware of the MRI findings at clinical follow-up. Coronal T1weighted spin echo coronal pulse sequences, T2-weighted turbo spin echo SPIR coronal pulse sequences (T2 fat suppressed), a single 10 mm thick single Spoiled Gradient Echo dynamic subtraction gadolinium-DTPA sequence, and a T1 SE post gadolinium-DTPA sequences of metacarpophalangeal joints 2–5 of the dominant hand were done. Films were scored under masked conditions independently by two musculoskeletal radiologists with consensus opinion in the event of disagreement. Soft tissue inflammation was scored as synovial where maximum in the

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.

Traumatic false aneurysm of a saphenous vein tributary in a cricketer.

The formation of a venous false aneurysm is an uncommon but well-recognized complication of trauma. Partial disruption of a vessel wall, after trauma, causes an outpouching of the traumatized portion of the vessel. Because of the blood flow from a feeder vein, this segment gradually expands, forming a false aneurysm. Patients with a venous false aneurysm may remain asymptomatic for a long period or report swelling over the area of recent injury. Alternatively, they may be seen with a complication of the false aneurysm, such as deep vein thrombosis, pulmonary embolism, rupture, or pain. Once a venous false aneurysm has been diagnosed, the management may vary from nonoperative treatment to surgical excision in symptomatic cases. A traumatic false aneurysm of the saphenous vein is a rare entity. We describe a case of a traumatic false aneurysm of a saphenous vein tributary, in which the patient, a cricketer, came in with swelling over the left medial malleolus. It is rare for a traumatic false aneurysm to occur in this area; nevertheless, this diagnosis should be among the differential diagnosis of a posttraumatic swelling.