61 Prevention of rheumatoid arthritis Introduction Rheumatoid arthritis (RA) is an autoimmune disease that affects 0.5-1% of the population worldwide [1,2]. The onset can occur at any age, with a mean around 40-50 years. RA is characterized by symmetrical peripheral polyarthritis in the hands and/ or feet, usually accompanied by systemic inflammation and other clinical manifestations. In untreated or non-responsive patients the inflammatory process eventually results in joint destruction, in some cases resulting in severe disability [3,4]. RA is also associated with an increased risk of cardiovascular disease and interstitial lung disease [5,6]. RA has a big impact on both the individual and the society. While it is possible for some patients to reach remission, not all patients respond to treatment. In addition to the patients affliction this can result in loss of work productivity and impairment of social activities. Even those who do respond are subjected to life-long treatment with costly therapies. There are two major subtypes of RA, based on the presence or absence of autoantibodies against specific antigens, most notably IgM-rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA). In general, ACPA-positive patients have earlier onset of disease (i.e. at younger age) than ACPA-negative patients, and often display a more severe clinical disease [7]. In line with this, ACPA-positive patients also have lower remission rates after initiation of disease-modifying anti-rheumatic drug (DMARD) treatment and more joint damage, although clinical manifestations at diagnosis are often indistinguishable between ACPA-positive and ACPA-negative patients [8]. In the evolution from healthy to full-blown RA different disease phases can be discriminated: an initial at-risk period (with genetic and/or environmental risk factors), a phase of clinically silent autoimmunity (e.g. the presence of ACPA), followed by clinically suspicious arthralgia (CSA), undifferentiated arthritis (UA), early RA, and established RA [9,10]. However, some phases might not be seen in all the patients. Seropositive and seronegative patients have overlapping but distinct risk factors [11]. The preclinical at-risk phase of seropositive individuals is characterized by immune system activation, production of autoantibodies and non-specific musculoskeletal signs and symptoms, mostly arthralgia [12]. Moreover, individuals may experience fatigue, pain, and transient swelling of the joints [13]. Both circulating antibodies and high levels of C-reactive protein (CRP), indicating some level of systemic inflammation, can be found up to five years before RA onset and signify an elevated risk of developing RA [14,15]. 4
RkJQdWJsaXNoZXIy MTk4NDMw