ニボルマブ投与後に発症した筋炎合併重症筋無力症の1剖検例
症例は84歳女性．腎細胞癌に対しニボルマブが投与された13日後より複視，眼瞼下垂，四肢脱力，嚥下障害が出現し，高CK血症を伴った．塩酸エドロフォニウム試験及び反復刺激検査での漸減現象から重症筋無力症と診断した．抗アセチルコリン受容体抗体は陰性であった．IVIg及びステロイドの投与にてCK値は正常化したが，身体症状は改善せず，呼吸不全で死亡された．剖検にて，腸腰筋と横隔膜の筋線維周囲にCD8陽性T細胞を主とした炎症細胞の浸潤が認められ，少数のCD4陽性T細胞も観察された．心筋に炎症細胞の浸潤を認めなかった．ニボルマブ投与後の筋炎合併重症筋無力症の剖検例は報告されておらず，貴重な症例と考えられた．...
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| Published in | 臨床神経学 Vol. 59; no. 6; pp. 360 - 364 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本神経学会
2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0009-918X 1882-0654 |
| DOI | 10.5692/clinicalneurol.cn-001282 |
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| Abstract | 症例は84歳女性．腎細胞癌に対しニボルマブが投与された13日後より複視，眼瞼下垂，四肢脱力，嚥下障害が出現し，高CK血症を伴った．塩酸エドロフォニウム試験及び反復刺激検査での漸減現象から重症筋無力症と診断した．抗アセチルコリン受容体抗体は陰性であった．IVIg及びステロイドの投与にてCK値は正常化したが，身体症状は改善せず，呼吸不全で死亡された．剖検にて，腸腰筋と横隔膜の筋線維周囲にCD8陽性T細胞を主とした炎症細胞の浸潤が認められ，少数のCD4陽性T細胞も観察された．心筋に炎症細胞の浸潤を認めなかった．ニボルマブ投与後の筋炎合併重症筋無力症の剖検例は報告されておらず，貴重な症例と考えられた． |
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| AbstractList | 症例は84歳女性．腎細胞癌に対しニボルマブが投与された13日後より複視，眼瞼下垂，四肢脱力，嚥下障害が出現し，高CK血症を伴った．塩酸エドロフォニウム試験及び反復刺激検査での漸減現象から重症筋無力症と診断した．抗アセチルコリン受容体抗体は陰性であった．IVIg及びステロイドの投与にてCK値は正常化したが，身体症状は改善せず，呼吸不全で死亡された．剖検にて，腸腰筋と横隔膜の筋線維周囲にCD8陽性T細胞を主とした炎症細胞の浸潤が認められ，少数のCD4陽性T細胞も観察された．心筋に炎症細胞の浸潤を認めなかった．ニボルマブ投与後の筋炎合併重症筋無力症の剖検例は報告されておらず，貴重な症例と考えられた． |
| Author | 小川, 将司 荒若, 繁樹 澤井, 大樹 重清, 太郎 細川, 隆史 佐野, 恵理 |
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| References | 16) 此枝史恵，鈴木重明，西本祥仁ら．ニボルマブ投与後に筋炎合併重症筋無力症を発症した1例．臨床神経 2017;57:373-377. 4) Zimmer L, Goldinger SM, Hofmann L, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 2016;60:210-225. 13) Kimura T, Fukushima S, Miyashita A, et al. Myasthenic crisis and polymyositis induced by one dose of nivolumab. Cancer Sci 2016;107:1055-1058. 6) Maeda O, Yokota K, Atsuta N, et al. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis. Nagoya J Med Sci 2016;78:119-122. 15) Hasegawa Y, Kawai S, Ota T, et al. Myasthenia gravis induced by nivolumab in patients with non-small-cell lung cancer: a case report and literature review. Immunotherapy 2017;9:701-707. 9) Polat P, Donofrio PD. Myasthenia gravis induced by nivolumab therapy in a patient with non-small-cell lung cancer. Muscle Nerve 2016;54:507. 14) Touat M, Maisonobe T, Knauss S, et al. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology 2018;91:985-994. 11) Bourgeois-Vionnet J, Joubert B, Bernard E, et al. Nivolumab-induced myositis: a case report and a literature review. J Neurol Sci 2018;387:51-53. 8) Shirai T, Sano T, Kamijo F, et al. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma. Jpn J Clin Oncol 2016;46:86-88. 3) Cuzzubbo S, Javeri F, Tissier M, et al. Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer 2017;73:1-8. 5) Suzuki S, Ishikawa N, Konoeda F, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 2017;89:1127-1134. 2) Wang PF, Chen Y, Song SY, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol 2017;8:730. 7) Mitsune A, Yanagisawa S, Fukuhara T, et al. relapsed myasthenia gravis after nivolumab treatment. Intern Med 2018;57:1893-1897. 1) Hashem OA, Samaresh S, Rami A, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcom. Front Pharmacol 2017;8:561. 12) Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 2016;375:1749-1755. 10) Takamatsu K, Nakane S, Suzuki S, et al. Immune checkpoint inhibitors in the onset of myasthenia gravis with hyperCKemia. Ann Clin Transl Neurol 2018;5:1421-1427. |
| References_xml | – reference: 9) Polat P, Donofrio PD. Myasthenia gravis induced by nivolumab therapy in a patient with non-small-cell lung cancer. Muscle Nerve 2016;54:507. – reference: 14) Touat M, Maisonobe T, Knauss S, et al. Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer. Neurology 2018;91:985-994. – reference: 16) 此枝史恵，鈴木重明，西本祥仁ら．ニボルマブ投与後に筋炎合併重症筋無力症を発症した1例．臨床神経 2017;57:373-377. – reference: 11) Bourgeois-Vionnet J, Joubert B, Bernard E, et al. Nivolumab-induced myositis: a case report and a literature review. J Neurol Sci 2018;387:51-53. – reference: 12) Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 2016;375:1749-1755. – reference: 10) Takamatsu K, Nakane S, Suzuki S, et al. Immune checkpoint inhibitors in the onset of myasthenia gravis with hyperCKemia. Ann Clin Transl Neurol 2018;5:1421-1427. – reference: 15) Hasegawa Y, Kawai S, Ota T, et al. Myasthenia gravis induced by nivolumab in patients with non-small-cell lung cancer: a case report and literature review. Immunotherapy 2017;9:701-707. – reference: 6) Maeda O, Yokota K, Atsuta N, et al. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis. Nagoya J Med Sci 2016;78:119-122. – reference: 4) Zimmer L, Goldinger SM, Hofmann L, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 2016;60:210-225. – reference: 3) Cuzzubbo S, Javeri F, Tissier M, et al. Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer 2017;73:1-8. – reference: 8) Shirai T, Sano T, Kamijo F, et al. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma. Jpn J Clin Oncol 2016;46:86-88. – reference: 1) Hashem OA, Samaresh S, Rami A, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcom. Front Pharmacol 2017;8:561. – reference: 2) Wang PF, Chen Y, Song SY, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol 2017;8:730. – reference: 7) Mitsune A, Yanagisawa S, Fukuhara T, et al. relapsed myasthenia gravis after nivolumab treatment. Intern Med 2018;57:1893-1897. – reference: 5) Suzuki S, Ishikawa N, Konoeda F, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 2017;89:1127-1134. – reference: 13) Kimura T, Fukushima S, Miyashita A, et al. Myasthenic crisis and polymyositis induced by one dose of nivolumab. Cancer Sci 2016;107:1055-1058. |
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| Title | ニボルマブ投与後に発症した筋炎合併重症筋無力症の1剖検例 |
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