Rare, but Severe: Vasculitis and Checkpoint Inhibitors

In the last years, immunotherapy has become a mainstay of cancer treatment. Owing to its increasing application in clinical practice, novel and rare, but severe, immune-related adverse events such as vasculitis are now being described more frequently. Vasculitis occurs as part of a primary immune disorder but might be induced additionally by substances such as checkpoint inhibitors, which boost the immune system, and thus can also appear as an immune-related adverse event. Several lines of evidence indicate that checkpoint proteins such as programmed death-1 (PD-1) play a major role in the pathophysiology of vasculitis. Such immune checkpoints serve to prevent autoimmunity and to maintain tolerance. We present a case of pronounced vasculitis in a patient with metastatic urothelial carcinoma who received pembrolizumab, and discuss potential pathomechanisms regarding how checkpoint inhibitors can mediate immune-related vascular toxicity. PATIENT SUMMARY: In this report, we looked at potential interactions between checkpoint inhibitors and immune-associated vascular adverse events. Immunotherapy-induced changes of the immune status can favor the occurrence of vascular disease, being fatal in most cases. We conclude that the risk of progressive vascular damage and identification of patients with pre-existing vascular disease should always be borne in mind when treating patients with immunotherapy.