Recurrent pseudogout after therapy with immune checkpoint inhibitors: a case report with immunoprofiling of synovial fluid at each flare

Abstract

Background Despite ground-breaking clinical success in the treatment of different cancers, immune checkpoint inhibitors can cause profound inflammatory and immune-related adverse events. Autoimmune inflammatory arthritis following immune checkpoint inhibitor treatment has been reported; however, to date, no cases of crystal arthritis following immune checkpoint inhibitors have been identified. Case presentation We report the first case of recurrent pseudogout, an inflammatory crystal arthritis, in a patient treated with nivolumab, a PD-1 inhibitor, for renal cell carcinoma. The patient had recurrent pseudogout flares about week to 10 days after each nivolumab infusion. After treatment with prophylactic colchicine, the patient well tolerated additional nivolumab infusions without adverse events. In parallel, we characterized immune cells of synovial fluid at each flare. Immunoprofiling of synovial fluid showed that the proportion of inflammatory IL-17-producing CD4 + T cells and amount of IL-17 were notably increased in synovial fluid with every recurrent flair, and correlated with the increase in number of synovial neutrophils, suggesting a potential role of T helper 17 (Th17) cells in neutrophil-driven inflammation during pseudogout arthritis. Conclusions This case suggests a potential influence of Th17 cells on the neutrophil recruitment and neutrophil-driven inflammatory events leading to pseudogout induced by immune checkpoint inhibitor therapy.

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

“… 79 The first observation of recurrent pseudogout flares 7 to 10 days after each nivolumab infusion has been recently reported. 80 …”

“…79 The first observation of recurrent pseudogout flares 7 to 10 days after each nivolumab infusion has been recently reported. 80 Several cases of myositis have been reported, with frequent limb-girdle myalgia and weakness that may mimic a PMR-like condition. [81][82][83] Because it represents a potentially life-threatening complication, the task force decided to formulate a dedicated recommendation on myositis (recommendation 8).…”

Immune checkpoint inhibitor treatment and atherosclerotic cardiovascular disease: an emerging clinical problem

“…63 Whether colchicine has the potential to reduce ICIassociated atherosclerosis is currently unknown, but it has been reported that colchicine prevented recurrent ICI-associated inflammatory arthritis in a patient who received the PD1 inhibitor nivolumab for renal cell carcinoma. 64 The well-known and favorable safety profile, oral availability and inexpensiveness may further increase the clinical applicability of this drug.…”

Expert Perspective: Immune Checkpoint Inhibitors and Rheumatologic Complications

“…There are reports of patients experiencing "activated OA," with more pain and swelling at joints previously affected by OA (11,18). Crystalline arthritis, particularly calcium pyrophosphate disease (19,20), was also reported in patients being treated with ICIs. We ask patients about all past musculoskeletal, inflammatory, and autoimmune diagnoses, with particular attention to prior injuries and surgeries, OA, and crystalline arthritis.…”