1.1. Epidemiology

Rheumatoid arthritis (RA) is an inflammatory process that may lead to disability as a result of joint destruction. The prevalence of RA is less than 1% in the general population and women are affected three times more as men but this sex difference weakens in the elderly. The onset of the disease is mostly during the fourth and fifth decades. Family studies have indicated a genetic predisposition with an increased frequency of the disease among the first-degree relatives and twins [1]. An association with human leukocyte antigen (HLA)-DR4 was shown in 70% of the Caucasian and Japanese patients compared to 28% of the controls [2, 3]. The discovery of rheumatoid factor (RF) in 1940s, led to hopes that blood tests could provide gold standard biomarkers in the recognition of the disease [4]. Approximately 70% of RA patients have a positive RF or anti-cyclic citrullinated peptide antibodies (ACPA) along with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) [5–7].

(b) soft-tissue swelling of three or more joints at least 6 weeks, (c) swelling of the proximal interphalangeal, metacarpophalangeal or wrist joints for at least 6 weeks, (d) symmetric joint swelling for at least 6 weeks, (e) rheumatoid nodules, (f) RF positive blood test and (g) radiographic changes like erosions or osteopenia in hand and wrist joints. These criteria are widely accepted for the diagnosis, but have a limitation in that they were derived for trying to discriminate patients with RA from those with a combination of other rheumatologic diagnosis. Early identification in the patients was not possible with the use of these criteria. In 2010, a joint working group of the ACR and the European League Against Rheumatism (EULAR) was formed to develop a new classification for RA. The newly developed criteria's were designed also as a referral tool for primary care physicians. The number of joints involved, small or large joints, serology (RF, negative or positive ACPA, CRP, ESR) and the duration of symptoms are noted. Every possibility has different points. If the patient has more than six points, the patient

The Rheumatoid Shoulder: Current Surgical Treatments http://dx.doi.org/10.5772/intechopen.71452 171

A. Joint Involvement Score 1 Large Joint 0 2–10. Large joints 1 1–3 Small Joints (with/without involvement of large joints) 2 4–10 Small joints (with/without involvement of large joints) 3 >10 Joints (at least one small joint) 5 B. Serology† Score Negative rheumatoid factor and negative anti-citrullinated protein antibody 0 Low-positive rheumatoid factor or low-positive anti-citrullinated protein antibody 2 High-positive rheumatoid factor or high-positive anti-citrullinated protein antibody 3 C. Acute-phase reactants† Score Normal C-reactive protein and normal sedimentation rate 0 Abnormal C-reactive protein or abnormal sedimentation rate 1 D. Duration of symptoms Score <6 weeks 0 ≥6 weeks 1

has a definitive RA [17] (Table 1).

Classification criteria for Rheumatoid Arthritis\*, \*\*

Score-based algorithm: add score of categories A–D.

At least one test is needed for classification.

rheumatoid arthritis [17].

\*\*A score of ≥6/10 is needed for classification of a patient as having definite rheumatoid arthritis.

Table 1. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for

1. Have at least one joint with definite clinical synovitis (swelling) 2. With the synovitis not better explained by another disease

Who should be tested? Target population

\*

†

New Genome-Wide Association Studies (GWAS) showed a total of 101 single nucleotide polymorphisms (SNPs) associated with immune dysregulation and inflammation. T-reg cells seem to be defective in RA patients [8]. Also, GWAS studies identified potential therapeutic targets. One study showed RA risk in a special pathway, which is called kappa B signaling pathway (NF-kB). Engagement of CD40 is one of the ways this pathway can be triggered and can be targeted for treatment [9]. Another new treatment method focuses on the Janus kinase (JAK) pathway [10]. This pathway is the main signaling mechanism in response to many cytokines involved in RA, including IL-6 [11]. Human leukocyte antigen (HLA) class II locus is associated less with the risk of developing ACPA and more ACPA-positivity to have RA [12]. In the recent years, environmental factors like smoking and pulmonary inflammation was shown to be associated with the emergence of the disease [13]. By using new methods that integrate genetic data with biochemical pathways and cell types involved in the disease, real progress has been made about RA pathophysiology like where and when immune tolerance is broken, which results in synovial inflammation and bone destruction [14]. Environmental factors needs to be recognized and their role in breaking RA tolerance should be investigated further [15].
