# Paraneoplastic Remitting Seronegative Symmetrical Synovitis With Pitting Edema: A Systematic Review of Case Reports and Observational Studies on Clinical Features, Treatment Response, and Outcomes

## TL;DR

This study reviews cases of a rare inflammatory condition called RS3PE that is linked to cancer, highlighting its symptoms, cancer associations, and treatment outcomes.

## Contribution

The paper systematically reviews clinical features and outcomes of paraneoplastic RS3PE, emphasizing its role as a cancer marker.

## Key findings

- RS3PE is strongly associated with malignancies like prostate, lung, and gastrointestinal cancers.
- Corticosteroid response rates vary by region, with higher remission rates in Japanese and U.S. cohorts.
- RS3PE often coincides with cancer diagnosis, suggesting it is a sentinel marker for malignancy.

## Abstract

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is an uncommon inflammatory disorder that may occur as a paraneoplastic manifestation. To clarify its clinical profile, we reviewed published cases and observational studies reporting paraneoplastic RS3PE. A total of 120 patients were identified, including 40 individual case reports and four observational cohorts. The mean age was 69 years, and men accounted for approximately 70-80% of patients. Associated malignancies were diverse, with prostate (22%), lung (18%), and gastrointestinal cancers (16%) being the most frequent among solid tumors, alongside hematologic malignancies such as lymphoma and leukemia (12%). The hallmark clinical presentation was symmetrical synovitis of the hands and feet with pitting edema. Systemic features were common, including fever (36%), weight loss (28%), and fatigue (21%). Corticosteroid responsiveness varied: pooled analysis demonstrated an overall response rate of 78.4%, but outcomes differed by region. For example, two Japanese and U.S. cohorts reported remission in over 85% of patients, whereas a Chinese cohort described only 42.8% achieving remission. Relapses were frequent and often paralleled cancer progression, reinforcing the link between RS3PE activity and malignancy status. In 59.5% of cases, RS3PE was diagnosed simultaneously with cancer, while in others it preceded (25%) or followed (15%) cancer diagnosis. These findings suggest that paraneoplastic RS3PE is a distinct clinical entity and a sentinel marker of malignancy. Comprehensive cancer screening should be prioritized in affected patients, particularly older men with systemic symptoms or inadequate steroid response. Further multicenter research is needed to establish biomarkers and optimize management strategies.