Brief Communication: Vogt-Koyanagi-Harada-like Syndrome Following CTLA-4 Inhibition with Ipilimumab for Metastatic Melanoma

摘要

Cytotoxic T-lymphocyte-associated antigen (CTLA-4) is a naturally occurring inhibitor of T-cell costimulation. Monoclonal antibody inhibition of CTLA-4 with ipilimumab blocks this negative regulator of costimulation, promoting T-cell activation and survival, and leads to melanoma regression. Findings of the Vogt-Koyanagi-Harada syndrome, an uveomeningitic syndrome that features neurologic, auditory, ophthalmologic, and cutaneous involvement due to autoimmune targeting of melanocytic antigen, have rarely been described in association with melanoma immunotherapy. We describe a case of Vogt-Koyanagi-Harada (VKH)-like syndrome in a 45-year-old HLA-A02-positive patient with metastatic melanoma treated with ipilimumab. Disruption of immune tolerance by ipilimumab led to melanoma remission while also inciting systemic and ophthalmic autoimmunity towards melanocytic antigen. These observations provide insight into the pathophysiology of the VKH syndrome, as well as the balance between tumor-associated tolerance and autoimmunity.