<scp>SONK</scp> ‐Like Subchondral Osteonecrosis Associated With Immune Checkpoint Inhibition

A 40-year-old woman with triple-negative breast cancer received combination immunotherapy with pembrolizumab, liposomal doxorubicin, and cyclophosphamide. During the third treatment cycle, she developed new-onset symmetrical polyarthritis involving both knees, shoulders, and elbows. An X-ray of the right knee showed only mild osteoarthritic changes (Figure 1A). However, magnetic resonance imaging (MRI) of the right knee revealed a focal lesion in the subchondral region of the medial femoral condyle and tibial plateau, with a characteristic double line sign on T2-weighted images (Figure 1B–D). What is the most likely diagnosis in this patient without corticosteroid use, trauma, or autoimmune disease? The MRI features were consistent with avascular necrosis, most likely representing spontaneous osteonecrosis of the knee (SONK)-like lesions. Although other potential causes such as steroid-induced osteonecrosis or metabolic risk factors were considered, these were ruled out based on the patient's history and laboratory data. While SONK is typically reported in elderly women and linked to mechanical overload or subchondral insufficiency fractures [1], this patient's presentation during immunotherapy raised the possibility of an immune-related vascular adverse event. Immune checkpoint inhibitors can promote endothelial inflammation by disrupting self-tolerance, leading to microvascular injury and local ischemia [2]. Notably, the MRI was obtained prior to corticosteroid therapy, which rapidly improved her polyarthritis. Similar vascular immune-related adverse events (irAEs) associated with immune checkpoint inhibitors have been previously reported in the literature [3, 4]. She had no known risk factors for osteonecrosis, including alcohol use, smoking, hyperlipidemia, or HIV infection [5]. This temporal relationship, together with the imaging findings, suggests a potential association between immune checkpoint inhibitor-induced endothelial dysfunction and localized ischemia in subchondral bone [3, 6, 7]. Conservative management was chosen, and no surgical intervention was required. Awareness of such bone-related immune adverse events is essential, particularly as immunotherapy becomes more common in oncology care. At six months follow-up, the patient's knee symptoms remained stable without progression on repeat imaging, and functional impact was minimal. Wan-Hao Tsai: data acquisition, image interpretation, and manuscript drafting. Ko-Jen Li: study conception, critical revision of the manuscript, and final approval. Both authors approved the final version and take responsibility for the integrity of the work. The authors thank the patient for her consent to share this case, and the medical staff involved in her care. The authors have nothing to report. Ethical approval was waived, as this is a single descriptive case report. The authors declare no conflicts of interest. The authors have nothing to report.