Checkpoint inhibitor–associated cutaneous small vessel vasculitis

Under physiologic conditions, immune checkpoints provide negative signals to control T-cell activation and prevent inflammation-associated tissue destruction. Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), a principal negative regulator of T-cell activation, binds to CD80/CD86 on antigen-presenting cells, dampening the stimulatory signal of CD28 on T cells. Programmed cell death 1 receptor (PD-1) is another inhibitive co-regulator of the CD28/CTLA4 pathway. Excessive activity of either of these checkpoints is one of the underlying mechanisms for cancers, such as melanoma, to evade the immune system.