The Diverse Fate of Seronegative Rheumatoid Arthritis Save

A Finnish Rheumatology Center followed 435 early, seronegative rheumatoid arthritis (RA) patients for 10-years and found that only 3% became erosive or seropositive RA. They also found that 32% could not be further reclassified, and that the remaining 65% evolve into another diagnosis, led by polymyalgia rheumatica (16%), psoriatic arthritis (11%), spondyloarthritis (9%), and osteoarthritis (10%).  

Between 1997-2005  they enrolled 1030 patients into the early RA clinic at the Jyväskylä Rheumatology Centre. They included 435 seronegative cases (42%), of whom 69% were women, and prospectively followed patients for a ten-year period.

Among the 435 seronegative cases, the 10-year outcomes revealed:

• 13 (3%) could be reclassified as seropositive or erosive RA
• 68 (16%) cases of polymyalgia rheumatica
• 46 (11%) psoriatic arthritis
• 47 (10.8%) seronegative spondyloarthritis 
• 45 (10%) osteoarthritis
• 38 (8.7%) spondyloarthritis
• 15 (3.4%) plausible reactive arthritis
• 10 (2.3%) gout
• 17 (3.9%) pseudogout
• 6 (1.4%) paraneoplastic arthritis
• 6 (1.4%) juvenile arthritis
• 2 (0.5%) haemochromatosis
• 3 (0.7%) ankylosing spondylitis
• 2 (0.5%) giant cell arteritis
• 8 miscellaneous diagnoses.
• 41 (9.4%) had transient arthritis
• 49 (11.2%) remained were not reclassifed.

After an initial diagnosis of seronegativity, prolonged follow-up revealed significant heterogeneity and reclassification of the inital diagnosis. Therefore seronegative arthritis should not be considered as a homogenous entity.

(Editor's note: This is a very interesting study. I'm amazed that only 14% kept a diagnosis of RA, but this may be a regional issue. While many Scandinavian cohorts such as these may have more seronegative spondyloarthritis patients manifesting as polyarthritis, the diversity of other subsequent diagnoses is interesting, if not humbling. One thing said by Dr. Ronan Kavanaugh on RheumNow some time ago was that "In seronegative patients in remission for years always consider withdrawing DMARD". I would add to that by saying you should always consider alternative diagnoses the longer you call someone "seronegative" RA.)