RS3PE Following Treatment With Combination of Hormonal Therapies Plus Ipilimumab in a Patient With Metastatic Prostate Cancer

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) are often associated with inflammatory toxicities known as immune-related adverse events (irAEs). Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is an atypical inflammatory arthritis. Herein, we report a case of RS3PE in a patient with metastatic prostate cancer who was receiving a combination of second-generation hormonal therapies plus ipilimumab.

Case presentation: A 59-year-old man with metastatic prostate cancer developed sudden onset of pain and swelling of the right hand after 15 weeks of treatment with second-generation hormonal therapies plus three cycles of ipilimumab. Symptoms alternated to the left hand. Physical examination showed tender, pitting edema of the left hand with tenderness on the right second through fifth metacarpal phalangeal joints, leading to the diagnosis of RS3PE. Ipilimumab was withheld, and the RS3PE self-resolved; however, 1 month later, the patient had another flare of RS3PE. A bone scan showed active inflammation on bilateral wrists and hands. Methotrexate was initiated, and his symptoms resolved over a few days. Methotrexate was discontinued 2 months later, and RS3PE has been in complete remission. His prostate cancer progressed, and radium-223 treatment was initiated.

Conclusion: To the best of our knowledge, this is the first reported case of RS3PE after the combined second-generation hormonal therapy plus ipilimumab. Both rheumatologists and oncologists should be aware that RS3PE can develop as an irAE. Understanding the mechanism of ICI therapy-associated RS3PE is critical to identify predictive biomarkers and develop optimal therapeutic strategies that do not sacrifice antitumor immunity.

Keywords: RS3PE; checkpoint inhibitors; immune-related adverse events; ipilimumab; prostate cancer.

Figure 1

Clinical presentation of remitting seronegative symmetrical synovitis with pitting edema induced by ipilimumab at the time of active symptoms (left) and 4 months after the completion of methotrexate therapy (right). Arrows and circles show swollen joints (arrows) and pitting edema (circles).

Figure 2

Technetium-99m MDP bone scan images before the development of remitting seronegative symmetrical synovitis with pitting edema (RS3PE; left), at the time of RS3PE flare (middle), and 4 months after completion of methotrexate therapy (right). Arrows show active synovitis of bilateral wrists and MCPs at the time of RS3PE flare. They also show sites of bone metastases in the right hemipelvis, both ischial tuberosities, and several left ribs. MCP: Metacarpophalangeal joint.

Figure 3

Posterior-anterior radiographs of bilateral hands and wrists at the time of remitting seronegative symmetrical synovitis with pitting edema flare, showing no bony erosive changes.