**Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis**

**Misako Higashida-Konishi 1,\*, Keisuke Izumi 1,2, Satoshi Hama 1, Hiroshi Takei 1, Hisaji Oshima <sup>1</sup> and Yutaka Okano <sup>1</sup>**


**Abstract:** In seronegative arthritis with extremity edema, it is difficult to differentiate between remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) and seronegative rheumatoid arthritis (SNRA). We compared the clinical characteristics of RS3PE and SNRA in patients with and without malignancies. We retrospectively examined patients diagnosed with RS3PE (McCarty criteria) and SNRA at our hospital in 2007–2020. Malignancy was diagnosed within 2 years before or after RS3PE or SNRA diagnosis. Overall, 24 RS3PE and 124 SNRA patients were enrolled. The median ages were 79.5 and 68.5 years, and men comprised 54.2% and 37.1% of RS3PE and SNRA patients, respectively. RS3PE patients had higher inflammation levels (*p* = 0.004) and more incidences of malignancy (*p* = 0.034). Matching for age and sex, RS3PE patients had higher inflammation levels (*p* = 0.021) and more incidences of malignancy (*p* = 0.005). Overall, odds ratios (ORs) for malignancy were higher for older age (OR 1.06, *p* = 0.037), male sex (OR 4.34, *p* = 0.007), RS3PE patients (OR 4.83, *p* = 0.034), and patients with extremity edema (OR 4.83, *p* = 0.034). Inflammation levels and associated factors of malignancy were higher in RS3PE patients than in SNRA patients. Patients who are older, male, with extremity edema, or had RS3PE should be screened for malignancies.

**Keywords:** rheumatoid arthritis; synovitis; neoplasms; edema; inflammation
