Abstract
Rheumatoid arthritis (RA) is being considered a multistep process. Certain genetic background along with environmental risk factors result to the break of immune tolerance and trigger autoimmune processes associated production of autoantibodies.
These are followed by first symptoms without any apparent arthritis and then first manifestation of clinically detectable arthritis - either undifferentiated or fulfilling criteria for definite RA. Despite joints being the typical site of manifestation of RA, the pathogenesis of the disease starts off far away of any joint structures.
It is suggested that first immunopathogetic processes start in the lungs or other mucous barrier such as periodont. This theory is supported by normal synovial tissue obtained from the joints of otherwise healthy carriers of anti-citrullinated protein antibodies (ACPA).
ACPA can be detected in blood months or even years before the first manifestation of RA. Combination of ACPA and rheumatoid factors are associated with 10x higher risk of developing RA in comparison with individuals lacking these autoantibodies.
Knowledge of the pathogenesis of RA brings the threshold for diagnosis, treatment or measures aiming for prevention of the development of RA to earlier stages even before the first manifestation of arthritis - pre-clinical stages of RA (pre-RA). The EULAR definition characterizing individuals considered at risk of progression to RA (clinically suspect arthralgia, CSA) unifies the clinical characteristics of these individuals and future patients.
At present, this definition is used for research purposes and clinical trials. This new perspective of looking at pre-RA is appreciated in ongoing clinical trials aiming for delay or even prevention from manifestation of RA using different treatment approach