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The Journal of Musculoskeletal Medicine.
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Modern serological tests and imaging may reduce the time to diagnosis 

Spotting the early warning signs of aggressive RA

By JANE FREESTON, MB BChir
ANNE-MAREE KEENAN
PAUL EMERY, MD, MB BChir | February 24, 2008
Dr Freeston is specialist registrar in rheumatology; Ms Keenan is a research fellow, academic unit of musculoskeletal disease; and Dr Emery is ARC professor of rheumatology and head, academic unit of musculoskeletal disease, in the Research School of Medicine, Chapel Allerton Hospital, the Leeds Teaching Hospitals, in Leeds,West Yorkshire, United Kingdom. For this article, the authors updated their discussion of early RA diagnosis first published in 2005 in The Journal of Musculoskeletal Medicine.

In addition, Raza and colleagues15 investigated the combination of RF and anti-CCP in patients with synovitis of 3 months’ duration. They showed that the combination had a high specificity and positive predictive value for the development of persistent RA.

IMAGING MODALITIES

Plain-film radiography

Because radiography is both relatively inexpensive and widely available, it is currently the marker for structural damage in RA. Hand and foot x-ray films are chosen because these anatomical areas are amenable to quantification and joint destruction is known to occur in them early in the disease course. The images now may be digitally recorded and retrieved; this allows for electronic transmission and standardized reading with reproducible scoring systems in the research setting.

Radiographs can detect many pathologic changes, such as erosions, joint-space narrowing, periarticular osteoporosis, and subluxation. However, in the earliest stages of RA, when the patient is pre-erosive, they are not helpful. In addition, they cannot detect soft tissue changes, such as the presence of synovitis. As a result, increasing interest has been directed toward use of MRI and musculoskeletal ultrasonography, which can identify such pathology at an earlier stage.

MRI

This is the most sensitive imaging modality, and its tomographic quality—including 3 orthogonal planes—helps provide a much greater field of view. MRI produces a highly detailed view of both the bony aspect of the joint and the surrounding soft tissues without exposing the patient to ionizing radiation—a considerable advantage over plain-film radiography, although disadvantages of MRI include high cost and lack of availability.

MRI is now available in several field strengths: the conventional high-field 1.5 Tesla magnet, the higher field 2 Tesla, and the new low-field 0.2 Tesla dedicated extremity. Sequences used in routine high-field MRI of musculoskeletal structures include T1-weighted images, which provide good anatomical detail; T2-weighted images, in which fluid/edema and fat produce a high signal; T2-weighted fat-suppressed images, in which bone edema is highlighted; short tau inversion recovery images; and T1 images obtained after intravenous injection of the contrast agent gadolinium. The gadolinium is preferentially taken up at sites of inflammation, such as synovitis; this allows for delineation from fluid collection and results in greater sensitivity in erosion detection.

Ostergaard and associates16 showed that MRI can identify most new bone erosions at least 1 year earlier than can conventional radiography. They found a significantly increased risk of progression of radiographic erosions in bones with baseline MRI erosions; this shows that MRI has value in prognosis of long-term radiographic outcome. In addition, MRI can identify pre-erosive features, such as synovitis and bone edema,17 and it allows for the identification of progressive erosive disease when clinical activity is suppressed.18

The Outcome Measures in Rheumatology Clinical Trials MRI collaborative subgroup was set up to address interobserver variability and other issues. The subgroup has produced acceptable definitions and a valid scoring system for MRI findings in RA.19,20 The issue of validation in MRI has been addressed extensively with use of arthroscopy and synovial biopsy and comparison of them with MRI synovial volume estimates. This has been performed mainly in knees, as well as by mini-arthroscopy, macroscopic evaluation, and histology in the metacarpophalangeal (MCP) joints. Ostendorf and coworkers21 found that synovial enhancement postgadolinium on MRI correlated with macroscopic signs of synovitis and that joint-space narrowing on MRI was significantly correlated with bony changes on arthroscopy.

More work needs to be done before it can be concluded that MRI shows an accurate representation of erosive change, synovitis, and bone edema—the changes of inflammatory arthritis. MRI is more validated than ultrasonography as a technique, but currently available data suggest that findings on ultrasonography are equal to those on MRI when peripheral joints are assessed in patients with RA.22 Currently, therefore, MRI remains a research tool with no specific guidelines for use in individual patients, and its exact role in clinical practice remains to be defined.

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