Musculoskeletal ultrasound characteristics of checkpoint inhibitor-associated inflammatory arthritis

Background: Cancer immunotherapy with checkpoint inhibition (ICI) has revolutionized the treatment of solid cancers; however, it is associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. Here we report our experience with the use of point-of-care musculoskeletal ultrasound (MSKUS) and provide a description of MSKUS findings in patients with definite musculoskeletal irAEs. Methods: Patients >= 18 years who received ICI at the Mass General Cancer Center from 2010-2019 were referred to rheumatology by oncology for evaluation of musculoskeletal symptoms following ICI therapy. Fifty-five patients with suspected MSK irAEs had MSKUS performed and interpreted by the same ultrasonographer. Findings were reviewed and confirmed by a blinded US reader. US findings in patients with definite de novo MSK irAEs were reviewed and correlated with the presence or absence of documented clinical synovitis and with available synovial fluid analysis. Results: Thirty-four out of fifty-five patients (62%) had definite de novo irAE. Seven patients were identified with alternative etiologies assisted by diagnostic MSKUS. Twenty patients with definite de novo irAE had clinical evidence of synovitis at the time of the initial MSKUS examination, while 14 did not. Among patients with clinically evident synovitis, MSKUS examination confirmed inflammatory pathology in all patients. The most common MSKUS features identified were grade 2 or higher synovial thickening (80 %), hyperemia measured by color power Doppler (CPD) signal (70 %), and tenosynovitis (60 %). Among the 14 patients without clinically evident synovitis, inflammatory features were identified in 10 patients (71 %); the most common features identified were > grade 1 synovial proliferation, hyperemia and tenosynovitis. Of 15 patients who underwent synovial fluid analysis, 7 patients had synovial fluid cell counts < 2000 cells/<mu>L considered traditionally within the 'non-inflammatory' range, and all 7 patients were noted to have inflammatory MSKUS findings. Conclusion: Point-of-care MSKUS is a valuable tool in the evaluation of potential MSK irAEs. Our data demonstrates its ability to expediate early identification of subclinical synovitis and/or tenosynovitis even when synovial fluid analysis is within the traditional non-inflammatory range.