Vogt–koyanagi–harada Disease-Like Uveitis in a Patient With Advanced Melanoma Treated by Sequential Administration of Nivolumab and Dabrafenib/Trametinib Therapy

Abstract

Purpose: To describe a case of bilateral Vogt-Koyanagi-Harada (VKH)-like uveitis during treatment with dabrafenib and trametinib and three months after discontinuation of nivolumab for malignant melanoma, and discuss the possible (synergistic) role(s) of mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors in its pathophysiology.Methods: Retrospective case report with fluorescein angiography and optical coherence tomography.Results: A 55-year old patient with metastatic melanoma presented with a complaint of gradually worsening blurry vision in the right eye during treatment with dabrafenib and trametinib, three months after discontinuation of nivolumab. Based on the clinical examination, optical coherence tomography and fluorescein angiography findings, and a thorough laboratory work-up, he was diagnosed with a bilateral VKH-like uveitis without extraocular manifestations. The uveitis responded well to oral corticosteroids.Conclusion: Vogt-Koyanagi-Harada-like uveitis is a rare adverse effect of MAPK inhibitors and immune checkpoint inhibitors. Similar pathogenetic mechanisms including a drug-induced autoimmunity targeted against benign and malignant melanocytes may underlie MAPK inhibitor-induced and immune checkpoint inhibitors-induced VKH-like uveitis. In our report, the patient developed a VKH-like uveitis during MAPK inhibition therapy, four months after discontinuation of nivolumab. It is difficult to delineate whether MAPK inhibition alone was responsible for this adverse effect, or whether, on the contrary, potentiation occurred as a result of immune modulation by previous treatment with an immune checkpoint inhibitor. Further cases are needed to further clarify this latter hypothesis.

Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review

“…A study of individual case safety reports from the WHO international pharmacovigilance database found that ICIs and protein kinase inhibitors were the only drugs associated with druginduced VKH-like uveitis [68]. Our literature search yielded 24 retrospective studies, case reports, and case series analyzing VKH-like uveitis in the context of ICI therapy, totalling 41 patients [68][69][70][100][101][102][103][134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150]. Details of the included study data are found in Appendix B (Table A4).…”