Sonographic Signatures of Immune Checkpoint Inhibitor-Associated Musculoskeletal Adverse Events.

Sonographic Signatures of Immune Checkpoint Inhibitor-Associated Musculoskeletal Adverse Events.

Publication date: Jul 15, 2025

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0-no signs of inflammatory arthropathy or tendinopathy, 1-potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2-active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making.

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Concepts Keywords
Arthritis diagnostic tool
Clinics immune-related adverse events
Seventeen immunotherapy
Sonographic melanoma
White musculoskeletal ultrasound

Semantics

Type Source Name
disease MESH cancer
disease MESH arthritis
disease MESH polymyalgia rheumatica
disease MESH syndromes
disease MESH arthropathy
disease MESH tendinopathy
disease MESH inflammation
disease MESH synovial hypertrophy
disease MESH Melanoma
pathway KEGG Melanoma
disease MESH osteoarthritis
disease MESH causes
drug DRUGBANK Ipilimumab
disease MESH death
drug DRUGBANK Tretamine
disease MESH rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
disease MESH tenosynovitis
drug DRUGBANK Coenzyme M
disease MESH musculoskeletal diseases
disease MESH musculoskeletal pains
disease MESH Rheumatism
disease MESH edema
disease MESH enthesopathy
disease MESH osteophytes
drug DRUGBANK Cysteamine
disease MESH renal cell carcinoma
pathway KEGG Renal cell carcinoma
disease MESH breast cancer
pathway KEGG Breast cancer
disease MESH carcinoma
disease MESH endometrial carcinoma
disease MESH neuroendocrine carcinoma
disease MESH Lung Cancers
disease MESH Carpal Tunnel Syndrome
disease MESH clinical course
drug DRUGBANK Rituximab
drug DRUGBANK Adalimumab
drug DRUGBANK Prednisone
drug DRUGBANK Tocilizumab
drug DRUGBANK Methotrexate
drug DRUGBANK Hydroxychloroquine
drug DRUGBANK Sulfasalazine
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH Spondylitis
disease MESH Sicca Syndrome
drug DRUGBANK Nivolumab
disease MESH Psoriatic Arthritis
disease MESH Spondyloarthropathy

Original Article

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