Synovial Fluid in Checkpoint Inhibitor-Induced Inflammatory Arthritis

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of advanced malignancies, but they can cause a wide range of adverse effects, including inflammatory arthritis. Severe ICI-induced inflammatory arthritis (ICI-IA) is rare, and its distinguishing clinical features are not defined. We present a patient with metastatic urothelial carcinoma who developed severe, polyarticular inflammatory arthritis while being treated with an ICI. Arthrocentesis of native and prosthetic joints revealed a significantly elevated white blood cell (WBC) count with a neutrophil predominance. Antibiotics were discontinued when the extensive infectious workup remained negative, and the patient was diagnosed with ICI-IA. This presentation of ICI-IA had overlapping features with septic arthritis, resulting in high diagnostic uncertainty. We comprehensively reviewed all published literature on the clinical features of severe ICI-IA. In the literature, synovial fluid findings revealed variable WBC counts but consistently have a neutrophil predominance. Although severe cases are rare, 9 previously reported cases shared similarities, including polyarticular presentation, elevated inflammatory markers, and absence of other rheumatic disease. Severe ICI-IA appears to have significant clinical overlap with culture-negative septic arthritis. This case report and literature review emphasize that ICI-IA should not be ruled out based on the presence of synovial fluid with elevated WBC with a neutrophil predominance. Early steroid use should be considered. Keywords: checkpoint inhibitor, inflammatory arthritis, immune-related adverse effects.