Vogt-Koyanagi-Harada Disease-Like Uveitis during Nivolumab (Anti-PD-1 Antibody) Treatment for Metastatic Cutaneous Malignant Melanoma

Abstract

Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody that is used to treat metastatic cutaneous malignant melanoma. Although bilateral uveitis has been reported as a side effect of nivolumab administration, there are few reports of Vogt-Koyanagi-Harada disease (VKH)-like uveitis. We report such a case. A 63-year-old woman with metastatic cutaneous malignant melanoma experienced visual loss in both eyes 10 days after her second nivolumab injection. Her decimal best-corrected visual acuity (BCVA) was 0.7 in the right eye and 0.4 in the left eye. Examination revealed bilateral granulomatous keratic precipitates and posterior synechiae in the left eye. Optical coherence tomography showed multiple sites of serous retinal detachment (SRD) in the left eye and wavy retinal pigment epithelium in both eyes. Fluorescein angiography revealed multiple pinpoint-sized areas of leakage in both eyes and active leakage from the disc in her right eye. Indocyanine green angiography (IA) showed choroidal hyperfluorescence due to choroidal vascular leakage, with hypofluorescent dark spots during the late phase. These findings supported a diagnosis of VKH-like uveitis following nivolumab injections. Nivolumab was discontinued because of headache. Anterior chamber inflammation disappeared 3 weeks after starting topical corticosteroid treatment, and the SRD disappeared within 3 months. Her decimal BCVA recovered to 1.0 in the right eye and to 0.9 in the left eye. Also, the fluorescein angiography and IA findings had improved by 4 months. We concluded that careful follow-up is required after nivolumab treatment because VKH-like panuveitis might develop.

Vogt–Koyanagi–Harada disease-like uveitis following nivolumab administration treated with steroid pulse therapy: a case report

“…To the best of our knowledge, there have only been five published case reports from six NVKH patients until now [6][7][8][9][10] (Table 1).…”

Vogt-Koyanagi-Harada Disease (Uveomeningitic Syndrome)

“…Drug-induced VKH can occur as an ocular immune-related adverse event associated with immunotherapy for malignancy. These are predominantly monoclonal antibodies that activate T-cells by binding to inhibitory checkpoints, such as PD-1 (pembrolizumab, nivolumab), [42][43][44] PD-L1 (atezolizumab, avelumab, durvalumab), [44] and CTLA4 (ipilimumab), [44,45], but similar reactions have also been reported with melanoma-specific immunotherapy targeting BRAF (dabrafenib, etc.) and MEK (trametinib) [46,47].…”

“…and MEK (trametinib) [46,47]. Obata et al described that the clinical presentation of these reactions can include bilateral granulomatous keratic precipitates, multifocal serous retinal detachments, multiple pinpoint-sized areas of leakage with active leakage from the disc on FA, as well as patchy choroidal hyper-and hypo-fluorescence on indocyanine green angiography [42,44]. The diagnosis is supported by a thorough past medical history and medication review.…”

“…Newer biologic agents such as infliximab, adalimumab, rituximab, and interferon alpha for the treatment of VKH have been described in case reports only [62][63][64]. Interestingly interferon alpha (when used to treat hepatitis C) and other immunotherapies against specific targets cytotoxic t-lymphocyte-associated protein 4 (CTLA4), programmed cell death protein 1 (PD1) and IL2 activated T-cell treatments when used to treat melanoma or other malignancies may also induce VKH and therefore should be used with caution [42,43,45,64]. Due to the small sample size and retrospective nature of studies on biologic immunomodulatory therapy, currently, there is no formal guideline on their use in the treatment of VKH.…”

“…In those individuals with significant vitreous opacities or vitreous debris, a pars plana approach including vitrectomy and lensectomy may be required [19]. Table 2 Treatment options for VKH Treatment options Corticosteroids Oral prednisone, 1.0-1.5 mg kg À1 day À1 , in single or divided doses or intravenous methylprednisolone, 200 mg/day for 3 days or 1 g/day for 3 days, followed by oral prednisone taper over 6 months Immunosuppressive agents 10,42 Cyclosporine, 5 mg kg À1 day À1 Tacrolimus 0.1-0.15 mg kg À1 day À1 Cytotoxic agents 10,42 Methotrexate, 15-25 mg week À1 Azathioprine, 1-2.5 mg kg À1 day À1 Mycophenolate mofetil, 1-3 g/day Cyclophosphamide 1-2 mg kg À1 day À1 Chlorambucil 0.1 mg kg À1 day À1 with adjustment of dose every 3 weeks up to a maximum of 18 mg/day…”