Page 49 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk

HOW DOES ESTABLISHED RHEUMATOID ARTHRITIS DEVELOP
INTRODUCTION
The concept of “established rheumatoid arthritis” (RA) appears to be clear for the
clinician. The picture arises of a patient with a “longstanding disease” that has caused a 3 certain amount of joint and comorbid damage, and it remains in a fixed state with more
or less active disease. The counterpart is the concept of “early (rheumatoid) arthritis,”
a more fluid state of recent synovitis where everything is still possible, including spontaneous or induced complete remission. Although the contrasting states are
clear, the transition between them is gradual and less well-defined. It is reasonable to
expect that causative factors for RA also influence the course of the disease, in this case
the progression from early to established RA. For example, anti-citrullinated protein antibodies (ACPAs) are associated with both the risk of developing RA and the risk of a
severe, unremitting course of RA.
In this chapter, we review risk factors for the development of early RA and for the transition to established RA. The concept of undifferentiated arthritis (UA) as a separate entity in a continuum from health to RA is undergoing changes due to new definitions. Finally, we focus on efforts to prevent RA from occurring (primary prevention) or from progressing from UA to RA (secondary prevention).
Apart from the uncertainty over the transitions between the different phases of RA, there is also considerable uncertainty over the question whether rheumatoid arthritis (RA) is a modern or an ancient disease. The name RA first appears in the medical literature in 1876(1), and the first unequivocal description of RA dates from 1631(2). There is a scarcity of descriptions of the disease in Europe between 1700-1900(3). This, combined with the fact that evidence of erosions compatible with RA has been found in ancient skeletons in North America, but not in Europe or the Middle East(4), has led to the suggestion that RA may be a communicable disease brought to the Old World after contact with the New World(1). A good candidate factor for such an effect may be tobacco smoking, a habit imported from the New World that increased tremendously in the late 19th century followed by a decrease in the second half of the 20th century, roughly in parallel with changes in the incidence of RA.
RISK FACTORS FOR RA DEVELOPMENT
The risk of developing RA is determined by genetic susceptibility combined with environmental factors(5, 6). Certain environmental factors operate already early in life, and they may help to lay the foundation for autoimmunity. In a large part of those later developing seropositive RA, there is a phase of autoimmunity and subclinical inflammation, during which another transient cause of inflammation such as an infection is thought to trigger the onset of clinically apparent disease(7).
47