Is remitting seronegative symmetrical synovitis with pitting edema (RS3PE) a subset of rheumatoid arthritis?

Semin Arthritis Rheum. 2010 Aug;40(1):89-94. doi: 10.1016/j.semarthrit.2008.11.006. Epub 2009 Feb 13.


Objectives: To contrast and compare the spectrum of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) with rheumatoid arthritis (RA) using an illustrative case.

Methods: The relevant English literature of RS3PE was searched using the keywords "RS3PE" alone and in combination with terms such as neoplasia and rheumatic disease. Original and review articles were reviewed and the clinical setting was exemplified with a case report.

Results: RS3PE initially was reported to represent a form of RA. However, RS3PE has clinical features that are different from both early- and late-onset RA, such as lack of bony erosions and rheumatoid factor. RS3PE is thought to involve vascular endothelial growth factor, suggesting an infectious etiology, generally has an excellent prognosis, and is associated with neoplasia not commonly seen in RA, and the RA associated human leukocyte antigen (HLA) DRB1 genotype is absent.

Conclusions: Based on the clinical, laboratory, suspected infectious etiology, genetic differences, and types of associated malignancies, RS3PE appears to be a distinct entity rather than a subset of RA.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / diagnosis
  • Diagnosis, Differential
  • Edema* / diagnosis
  • Edema* / etiology
  • Edema* / immunology
  • Humans
  • Paraneoplastic Syndromes
  • Recurrence
  • Serologic Tests
  • Synovitis* / diagnosis
  • Synovitis* / etiology
  • Synovitis* / immunology
  • Vascular Endothelial Growth Factor A / immunology*


  • Vascular Endothelial Growth Factor A