ペムブロリズマブ投与中に脈絡膜剝離とVogt-小柳-原田病様のぶどう膜炎を生じた1例

A case of Vogt-Koyanagi-Harada disease-like uveitis with choroidal detachment induced by pembrolizumab treatment

要約　目的：免疫チェックポイント阻害薬であるペムブロリズマブ投与中に脈絡膜剝離とVogt-小柳-原田病様のぶどう膜炎を生じた1例の報告。

症例：82歳，女性。右鼻腔悪性黒色腫に対しペムブロリズマブ5クール投与中に両眼痛と視力低下を自覚し，近医で眼内隆起性病変を指摘され当科を紹介受診した。初診時の視力は右（0.3），左（0.5），眼圧は右9mmHg，左11mmHg。両眼に硝子体混濁と脈絡膜剝離を認め，網膜光干渉断層計で漿液性網膜剝離と脈絡膜皺襞を認めた。フルオレセイン蛍光眼底造影検査で両眼の斑状蛍光漏出と視神経乳頭の過蛍光を，インドシアニングリーン蛍光眼底造影検査で両眼の低蛍光斑を認めた。同時期より耳鳴と難聴が出現し，髄液検査ではリンパ球優位の細胞増加がみられ，HLA-DR4は陽性であり，ペムブロリズマブの副作用によるVogt-小柳-原田病様のぶどう膜炎と診断した。同薬を中止し脈絡膜剝離は消失したが，両眼の低眼圧，球結膜充血，虹彩炎，豚脂様角膜後面沈着物が認められ，本人の希望により副腎皮質ステロイド全身投与は行わず，点眼とテノン囊下注射にて治療を開始した。その後ぶどう膜炎は消失し，初診より14週間後の視力は両眼（1.0）に改善し，眼圧も正常化した。

結論：ペムブロリズマブによる汎ぶどう膜炎の治療には副腎皮質ステロイド全身投与が推奨されているが，本症例のような脈絡膜剝離を伴う強い汎ぶどう膜炎であっても同薬の中止と局所投与にて寛解したため，局所治療が全身治療に代用できる可能性がある。

Abstract　Purpose：This report presents a case of Vogt-Koyanagi-Harada disease-like uveitis with choroidal detachment induced by treatment with pembrolizumab, an immune checkpoint inhibitor.

Case：An 82-year-old woman, who was receiving five terms of pembrolizumab for malignant melanoma of the right nasal cavity, complained of bilateral eye pain and blurred vision and was referred by her primary care physician, who pointed out an intraocular protuberant lesion. The patient's corrected visual acuity was 0.3 in the right eye and 0.5 in the left eye, and the intraocular pressure was 9mmHg in the right eye and 11mmHg in the left eye. Both eyes showed vitreous opacity and choroidal detachment, and retinal optical coherence tomography showed serous retinal detachment and choroidal wrinkling. Fluorescein angiography showed mottled fluorescence leakage and hyperfluorescence of the optic nerve papillae in both eyes, and indocyanine green fluorescence angiography showed hypofluorescent spots in both eyes. Simultaneously, tinnitus and hearing loss developed, and spinal fluid examination showed increased lymphocyte-dominant cells and HLA-DR4 positivity, leading to the diagnosis of Vogt-Koyanagi-Harada disease-like uveitis due to the side effects of pembrolizumab. After discontinuation of the drug, choroidal detachment disappeared, but hypotony, hyperemia of the conjunctiva, iritis, and mutton fat keratic precipitates were observed in both eyes. At the patient's request, treatment with eye drops and sub-Tenon's triamcinolone acetonide injection started instead of systemic corticosteroid administration. Uveitis disappeared, the corrected visual acuity improved to 1.0 in both eyes, and the intraocular pressure normalized 14 weeks after the first visit.

Conclusions：Although systemic corticosteroid administration is recommended for the treatment of panuveitis with pembrolizumab, even strong panuveitis with choroidal detachment, such as in this case, was remitted by discontinuation of the drug and topical administration, suggesting that topical treatment may be an alternative for systemic treatment.