Objective: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune related adverse event (irAEs), our objective was to identify and describe cases of ICI associated RS3PE (ICI-RS3PE) and compare to non ICI-RS3PE.

Methods: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed.

Results: We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was non-small cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICIRS3PE, 3 had partial response and 1 had complete response. All patients received glucocorticoids. Conventional synthetic DMARDs (cs-DMARD) were needed in 10 patients.

Conclusion: ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.


Rouhi A, Jamal S, Arreola LG, Moon D, Hudson M, Roberts J, Ladouceur A, Ye C. Immune Checkpoint Inhibitor associated Remitting Seronegative Symmetrical Synovitis with Pitting Edema (ICI-RS3PE): Description of a New Entity by CanRIO. J Rheumatol. 2024 Mar 1:jrheum.2023-0969. doi: 10.3899/jrheum.2023-0969. Epub ahead of print. PMID: 38428960.