Systemic Sclerosis Induced by Immune Checkpoint Inhibitors from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO): A Case Series

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, improving outcomes in multiple advanced malignancies. Their use is often limited by immune-related adverse events (irAEs), including rare rheumatic irAEs, such as ICI-induced systemic sclerosis (ICI-SSc). Compared to idiopathic SSc, ICI-SSc typically presents with fewer extra-cutaneous manifestations and negative serologies, but data remains limited.[1] This case series describes the clinical presentation, management, and outcomes of patients with ICI-SSc to guide clinicians in balancing autoimmune toxicities with cancer control. A retrospective chart review was conducted on 7 adults diagnosed with systemic sclerosis following ICI exposure between March 2021 and August 2025. All patients were referred to a Canadian academic rheumatology clinic specializing in Immuno-Oncology during ICI therapy. Clinical data was abstracted from medical records, including patient demographics, malignancy type and stage, ICI type and duration, clinical features, serologies, treatment, and outcomes. Of the 7 patients identified, 5 (71.4%) were female and 2 (28.6%) were male, with a mean age (SD) of 63 (10.9) years. Malignancies included: metastatic melanoma (n=4), metastatic squamous cell carcinoma (n=1), breast cancer Stage IIA/IIB (n=1), and metastatic endometrial adenocarcinoma (n=1). ICIs used included: pembrolizumab (n=2), nivolumab (n=1), cemiplimab (n=1), and ipilimumab/nivolumab combination followed by nivolumab monotherapy (n=2), which were discontinued due to SSc symptoms within 1-13 months of initiation. Serologies showed ANA positivity in 4 patients (57.1%), with SSc-specific antibodies (anti-Scl-70) detected in 1 patient. Other antibodies detected included anti-RP-11, anti-RP-155, anti-Ro-52, anti-chromatin, and anti-OJ. 2 patients had negative serologies, 1 with elevated inflammatory markers. All patients had scleordactyl (diffuse 57.1%, limited 42.9%) and extra-cutaneous features, most commonly Raynaud’s phenomenon (71.4%). Other manifestations included inflammatory arthritis (42.9%), nailfold capillary changes (42.9%), esophageal dysmotility (28.6%), telangiectasia (14.3%), and sicca symptoms (14.3%). No patients developed interstitial lung disease, pulmonary arterial hypertension, or scleroderma renal crisis. Management included ICI cessation for all patients, prednisone (85.7%), disease-modifying antirheumatic drugs (mycophenolate mofetil 57.1%, methotrexate 28.6%, hydroxychloroquine 28.6%), infliximab and intravenous immunoglobulins, and vasodilatory therapies. All malignancies were stable at 6 months post-ICI therapy. ICI-SSc is a significant irAE primarily characterized by cutaneous manifestations but, in contrast to previous reports, this case series demonstrates that extra-cutaneous manifestations and seropositivity can occur. Along with ICI-cessation, immunosuppressive therapy was effective in symptom control without compromising cancer stability. This work may assist those involved in caring of patients with ICI-SSc to initiate immunosuppressive therapy and minimize the risk of end-organ complications. [1.] Cho LK. Rheum Dis Clin North Am 2024;50:301-12.