Spotting the early warning signs of aggressive RA

Spotting the early warning signs of aggressive RA


ABSTRACT: Recent advances in drug therapies for rheumatoid arthritis (RA) have increased the importance of early intervention. Several serological testing and imaging techniques help facilitate early diagnosis. C-reactive protein level and erythrocyte sedimentation rate have limitations in predicting RA. Rheumatoid factor acts as a prognostic marker for later joint damage in patients with early RA. Antibodies against cyclic citrullinated peptide can predict more erosive disease. Radiography currently is the marker for structural damage in RA, but it cannot detect soft tissue changes or actual cartilage deterioration. MRI is the most sensitive imaging modality. Ultrasonography has been shown to be more sensitive than conventional radiography in detecting erosions. (J Musculoskel Med. 2008;25:110-115)


Rheumatoid arthritis (RA) often presents late, when irreversible damage has occurred. More than half of primary care consultations are for joint pain,1 but the average time from initial presentation with symptoms to confirmation of diagnosis of RA is 18 weeks.2

 Recent advances in drug therapies for RA have increased the importance of early intervention. Therefore, early diagnosis has never been more critical. Many diagnostic tests are available; physicians should select them carefully in an effort to improve the time to diagnosis.

 Serological testing and imaging techniques are becoming increasingly useful in facilitating early diagnosis of RA and appropriate disease monitoring in primary care practice. Because there are so many tests, however, gaining an understanding of the value and application of each technique is difficult. In this article, we provide an overview of serological testing and imaging techniques and how they are applied in the diagnosis and management of early RA.


A major goal in the treatment of patients with RA is the prevention of erosive joint disease and the irreversible functional disability that might result from it.3 Combinations of disease-modifying antirheumatic drugs and, more recently, biologic agents (eg, those blocking tumor necrosis factor α) are used in clinical practice to achieve this goal. Key to the prevention of joint damage is the ability to identify inflammatory disease at the earliest time, when disease activity is reversible. Such early recognition of inflammatory disease and subsequent aggressive treatment allow for prevention or modulation of erosive disease to a less severe phenotype.

Physicians should have a high index of suspicion when patients present with key clinical symptoms (Table 1). Appropriate diagnostic tests should be ordered, but first it is important to consider the aims of any rheumatologic investigation: to assist with diagnosis, to provide guidance for prognosis, and to assess disease activity. Serological markers, including those that indicate diagnosis and prognosis, as well as radiographic, ultrasonographic, and computerized imaging techniques, are used to determine outcome measures in clinical trials.




Acute phase reactants

C-reactive protein (CRP) and other acute phase reactants are proteins that the liver produces in higher quantities as part of the acute phase response to an inflammatory stimulus. Erythrocyte sedimentation rate (ESR) is also used frequently as a measure of the acute phase response. ESR provides an indirect measure of the amount of fibrinogen in the blood; production of fibrinogen is increased as part of the acute phase. An elevated acute phase response has been shown to correlate with bone damage,4 loss of bone mineral density (BMD),5 and functional impairment, especially when it is analyzed as the “area under the curve” (that is, when it is expressed as cumulative exposure of the patient to an elevated CRP level, reflecting continuing inflammation).


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