on the Research Topic Risk factors for Rheumatoid Arthritis and pre-Rheumatoid Arthritis This Research Topic, entitled Risk factors for Rheumatoid Arthritis and pre-Rheumatoid Arthritis, is focused on understanding the myriad of etiological factors implied in the pathophysiology of RA, identifying possible preconditions of RA, as well as recognizing risk factors for the development of RA. Romão and Fonseca (a) and Romão and Fonseca (b), in two complementary reviews, highlight the fact that genetic factors account for a major proportion of disease risk, and are regulated by epigenetic mechanisms, which in turn can be modulated by environmental and hormonal factors. This means that, besides interfering via epigenetic mechanisms, hormonal and neuroendocrine factors along with comorbid conditions, further determine the host's disease susceptibility. In parallel, the at-risk subject constantly interacts with environmental factors such as airborne exposures, diet, microbiota, and infectious diseases. These interactions result in multiple pathophysiological changes that culminate in a loss of self-tolerance and subsequent autoimmunity and inflammation. This understanding allows not only the identification of a pre-clinical stage, but also the screening of subjects at high-risk of RA.Rheumatoid Arthritis (RA) disease progresses years before the onset of clinical arthritis (1). Undifferentiated arthritis (UA) was defined, retrospectively, as clinical arthritis (joint swelling observed upon physical examination), neither fulfilling the 1987 nor the 2010 RA criteria or any other clinical diagnosis. Symptoms such as pain in small joints and morning stiffness allow rheumatologists to identify patients at risk of developing RA and at this stage is defined as clinically suspect arthralgia or pre-RA. A study reported that 32% of people defined as pre-RA develop RA (2). C-reactive protein levels, ACPA-positivity, and subclinical MRI inflammation were Frontiers in Medicine frontiersin.org
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