Seronegative Arthritis More than One Disease


Patients who start out being diagnosed with seronegative arthritis probably won’t end up with seropositive rheumatoid arthritis (RA), researchers find.



Patients who start out being diagnosed with seronegative arthritis probably won’t end up with seropositive rheumatoid arthritis (RA). That’s what a group of investigators in Finland found when they followed 435 patients with seronegative arthritis for 10 years to an extraordinarily broad range of outcomes, many of which follow a milder course than progressive RA.

Positive identification in serum of rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) represent early RA markers that are indicative of a more severe course of disease. Seropositive RA has been associated with poorer response to therapy and worsened radiographic outcomes compared to seronegative disease.

The results of the current study, published by Paalanen et al. in January in Clinical and Experimental Rheumatology, were so striking in the heterogeneity of outcomes that the authors suggested that seronegative arthritis should no longer be studied as a singular entity. Although more than 50 percent of the seronegative cohort met clinical criteria for RA according to the 1987 ACR guidelines at baseline, only 2.9 percent went on to convert to seropositive RA.

Reclassified Outcomes

Information accumulated during the 10-year follow-up led to reclassification of the patient base into multiple other separate disease categories, including:

  • Polymyalgia and giant cell arteritis (15.6%)

  • Psoriatic arthritis (10.6%)

  • Osteoarthritis (10.3%)

  • Spondyloathritis and ankylosing spondyloarthritis (8.7%)

  • Reactive arthritis (3.4%)

  • Crystal arthritis (2.3%)

  • Paraneoplastic arthritis (1.4%)

  • Juvenile arthritis (1.4%)

Additionally, individual patients were reclassified as has having vasculitis, colitis ulcerosa-related arthritis, and other disease entities. More importantly, a large minority (32.2%) of the patients continued to have symptoms that could not be reclassified into any specific disease group.

Once the group of 435 patients was re-categorized, specific group characteristics emerged: the crystal arthritis group was all male, while the osteoarthritis, reactive arthritis, juvenile arthritis and paraneoplastic arthritis groups were predominantly female.  The authors also identified a rare, aggressive form of seronegative RA in 4 of the patients that resulted in severe joint destruction.

Many patients did not have severe disease courses, leading the authors to challenge conventional treatment guidelines call for aggressive early management of seronegative disease. “If seronegative patients are treated according to the treatment guidelines of progressive RA, a substantial portion of patients is [sic] exposed to unnecessary long-term medication,” they wrote.


Paalanen K, Rannio K, Rannio T, et al. "Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observational study." Clinical and Experimental Rheumatology. 2019 Jan-Feb;37(1):37-43.

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