Case Presentation: A 72-year-old male with lung adenocarcinoma in PET-confirmed remission developed rapidly progressive, symmetric inflammatory polyarthritis five months after completing immune checkpoint inhibitor (ICI) therapy with pembrolizumab. He reported diffuse joint pain, morning stiffness, fatigue, and functional decline involving multiple large and small joints. Examination revealed bilateral wrist and metacarpophalangeal synovitis, restricted wrist motion, shoulder tenderness, and bilateral knee effusions. Synovial fluid from the right knee showed WBC 15 x103/µL (70% neutrophils) with a negative Gram stain, culture, and crystal analysis. Rheumatoid factor, CCP, ANA, dsDNA, and antiphospholipid antibodies were negative. ESR was 70 mm/h and CRP 39 mg/L. Imaging demonstrated degenerative changes without erosion. Findings supported delayed-onset immune checkpoint inhibitor-associated inflammatory arthritis. He received intra-articular corticosteroids, a short oral steroid taper, and methotrexate 20 mg weekly with folic acid. Given marked fatigue, screening for myocarditis, myositis, and myasthenia was performed and negative. The patient had partial improvement following steroid therapy, and rheumatology-oncology follow-up was arranged.
Discussion: Immune checkpoint inhibitors have transformed oncologic care, and hospitalists may increasingly encounter immunotherapy-related adverse events. Early recognition of ICI-induced arthritis prevents unnecessary infectious workups and accelerates multidisciplinary care. Occurring in 1–7% of patients, ICI-induced arthritis may develop during therapy or months later. [4,5] Though resembling seronegative rheumatoid arthritis, it reflects therapy-driven immune dysregulation. [3] This patient’s symmetric synovitis, seronegativity, elevated inflammatory markers, and non-erosive imaging are typical. Excluding mimicking diseases is essential. Management aims to control inflammation without compromising cancer therapy. [2] Corticosteroids remain first-line, methotrexate as steroid-sparing with reassuring oncologic safety [1], and biologics for refractory cases under oncology oversight. [6] Screening for concurrent ICI toxicities (myocarditis, myositis, myasthenia) is warranted when fatigue or weakness occurs.
Conclusions: Hospitalists should maintain a high index of suspicion for immune-related adverse events in patients with prior immunotherapy exposure as delayed-onset ICI-associated polyarthritis can mimic common rheumatologic conditions and lead to misdiagnosis. A structured diagnostic approach including serologies, synovial fluid analysis, imaging, and screening for concurrent ICI toxicities supports accurate diagnosis and timely intervention. Multidisciplinary collaboration between hospitalists, rheumatologists, and oncologists is essential to balance inflammation control with cancer therapy continuity. Corticosteroids remain first-line, while methotrexate offers effective steroid-sparing benefits while reassuring oncologic safety. Biologics may be considered for refractory disease but require oncology oversight. Ultimately, proactive identification and coordinated management can improve patient function, reduce morbidity, and maintain cancer remission without compromising therapeutic goals.