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Nomenclature for the Phases of the Development of Rheumatoid Arthritis


Raza K1, Holers VM2, Gerlag D3. Clin Ther. 2019 Jul;41(7):1279-1285. doi: 10.1016/j.clinthera.2019.04.013. Epub 2019 Jun 10.

Author Information

1 Institute of Inflammation and Ageing, Arthritis Research UK Rheumatoid Arthritis Centre of Excellence, Medical Research Council Arthritis Research UK Centre for Musculoskeletal Ageing, University of Birmingham, Birmingham, United Kingdom; Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom. Electronic address: k.raza@bham.ac.uk.

2 Division of Rheumatology, University of Colorado-Denver, Aurora, CO, USA.

3 RxCelerate, Cambridge, United Kingdom.


Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease. Research on RA is increasingly focused on the earliest stages of the disease, and has provided strong evidence that clinical signs and symptoms may be preceded by a preclinical phase during which evidence of systemic autoimmunity may be present. To facilitate research in this area, a number of international initiatives have proposed definitions of the phases of disease leading up to RA. The first of these initiatives was the European League Against Rheumatism's (EULAR) set of recommendations on terminology in persons at risk for RA, which suggested that the "at-risk phases" be described in terms of patients variably having: (A) genetic risk factors for RA; (B) environmental risk factors for RA; (C) systemic autoimmunity associated with RA; (D) symptoms without clinical arthritis; and (E) unclassified arthritis. The phrase clinically suspect arthralgia (CSA) is now widely used and can be regarded as describing a subgroup of patients in phase D. A definition of CSA was recently proposed by a EULAR taskforce, and primary research has begun to explore the full range of symptoms, as well as their sensitivity and specificity alone and in combination with other factors, that characterize this phase. Similarly, immune abnormalities at mucosal and others sites that precede and/or are associated with the onset of musculoskeletal symptoms are being increasingly studied and understood. Whether some of these at-risk phases, in particular CSA, represent entities meriting their own classification criteria is an essential area for consensus and will be discussed.