Relapsing Polychondritis following PD-1 Blockade by an Immune Checkpoint Inhibitor

Immune-related adverse events (irAEs) mimicking rheumatic diseases are observed in 1.5%-22% of patients receiving cancer therapy with immune checkpoint inhibitors (ICIs). Relapsing polychondritis (RP) is a rare autoimmune disease mainly involving auricle, nose, and airway cartilage inflammation. However, knowledge regarding RP as an irAE is scarce. Pembrolizumab, a type of ICI that regulates the programmed cell death protein-1 (PD-1), is used in patients whose cancer cannot be cured with surgery or radiation therapy. We report the first case of pembrolizumab-induced RP with isolated auricular lesions resolved without immunosuppressants. A 49-year-old man with lower lip cancer underwent surgical resection followed by reconstruction. Histopathological investigation confirmed the diagnosis of squamous cell carcinoma. Since multiple metastases 6 months post-surgery rendered the carcinoma inoperative, pembrolizumab was initiated, improving lymph node involvement. However, 4 months later, the patient developed rapidly progressive swelling and pain in both auricles. While no pathogen was detected, C-reactive protein levels were elevated (11.21 mg/dL). Computed tomography (CT) showed swelling of the bilateral auricles; the biopsy of the right auricle revealed cartilage destruction by infiltration of surrounding granulation tissue. Since these characteristic findings were not observed before pembrolizumab was initiated, we clinically diagnosed the patient with RP induced by pembrolizumab. The swelling of the auricles resolved spontaneously 1 month after pembrolizumab discontinuation. (18)F-fluorodeoxyglucose ((18)F-FDG)-positron emission tomography/CT revealed no (18)F-FDG uptake in reduced auricular lesions. On re-administration of pembrolizumab to maintain antitumor immunity, both auricles swelled again, and pembrolizumab was switched to paclitaxel, considering the risk of tracheobronchial chondritis. Although no recurrence of auricular chondritis was observed, the patient died from cancer progression 8 months after paclitaxel administration. RP can occur as a rheumatic irAE in patients receiving anti-PD-1 therapy, and a literature review with retrospective analysis indicates that PD-1 inhibition-induced RP is unusual and atypical.