Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Neurology School of Medicine, Fukushima Medical University, Fukushima City, 960-1295, Japan.
BMC Neurol. 2019 Aug 5;19(1):184. doi: 10.1186/s12883-019-1416-1.
Pembrolizumab is an immune-checkpoints inhibitor that enhances the immune response against cancer cells and therefore is useful for the treatment of several carcinomas. However, pembrolizumab sometimes perturbs the immune system resulting in various autoimmune neurological complications. In this situation, autoimmune myositis due to pembrolizumab is a rare but not-negligible complication. Here, we report two cases of autoimmune myositis due to pembrolizumab, with systemic myositis involving levator palpebrae superioris, extraocular and hindneck muscles.
Case 1 was a 78-year-old man with advanced urinary cancer referred to the neurological ward presenting with bilateral ptosis, restriction of eye movements, dropped head and weakness in the lower extremities after pembrolizumab administration. His blood examination showed elevated serum levels of creatine kinase with positive anti-PM-Scl 75 and anti-signal recognition particle antibodies. Needle electromyography and MRI suggested systemic inflammatory myopathy. There were no findings to indicate myocardial involvement on electrocardiogram or echocardiogram. Administration of intravenous methylprednisolone following plasma exchange ameliorated creatine kinase levels and inhibited the progression of clinical symptoms. Case 2 was a 72-year-old female with lung cancer and multiple metastasis, including lymph nodes and brain. She presented with back pain, right-sided ptosis, weakness of her neck extensors and flexors and elevated serum creatine kinase after receiving pembrolizumab. Although myositis specific autoantibodies were negative, needle electromyography and MRI suggested systemic inflammatory myopathy and muscle biopsy indicated necrotizing myopathy. There were no signs indicating heart dysfunction and her electrocardiogram was normal. Clinical symptoms and serum creatine kinase levels were ameliorated after the administration of intravenous methylprednisolone.
Both cases showed atypical extensive inflammatory myositis including levator palpebrae superioris, extraocular and hindneck muscles, resembling myasthenia gravis (MG), but they did not have MG-related antibodies. Edrophonium test was negative and showed no daily fluctuation. Two previously reported cases also presented with systemic necrotizing systemic myositis involving extraocular and facial muscles caused by pembrolizumab. Idiopathic inflammatory myositis evolving levator palpebrae superioris and ocular muscles is quite rare; however, myositis due to immune-checkpoint inhibitors may preferentially involve these muscles. This case report will alert physicians to the possibility of systemic inflammatory myopathy evolving levator palpebrae superioris, extraocular and hindneck muscles mimicking MG due to pembrolizumab.
帕博利珠单抗是一种免疫检查点抑制剂，可增强机体对癌细胞的免疫反应，因此可用于多种癌的治疗。然而，帕博利珠单抗有时会扰乱免疫系统，导致各种自身免疫性神经系统并发症。在这种情况下，帕博利珠单抗引起的自身免疫性肌炎是一种罕见但不可忽视的并发症。本文报道了 2 例由帕博利珠单抗引起的自身免疫性肌炎，伴有累及提上睑肌、眼外肌和颈后肌的全身肌炎。
病例 1 为 78 岁男性，患有晚期膀胱癌，因帕博利珠单抗治疗后出现双侧上睑下垂、眼球运动受限、抬头无力和下肢无力，转至神经内科病房。患者血液检查示肌酸激酶升高，抗 PM-Scl 75 抗体和抗信号识别颗粒抗体阳性。肌电图和 MRI 提示全身性炎症性肌病。心电图和超声心动图无心肌受累的表现。行血浆置换联合静脉注射甲基泼尼松龙治疗后，肌酸激酶水平降低，临床症状得到抑制。病例 2 为 72 岁女性，患有肺癌和多处转移，包括淋巴结和脑转移。患者因帕博利珠单抗治疗后出现背痛、右侧上睑下垂、颈伸肌和颈屈肌无力及肌酸激酶升高。尽管肌炎特异性自身抗体阴性，但肌电图和 MRI 提示全身性炎症性肌病，肌肉活检提示坏死性肌病。无心脏功能障碍的迹象，心电图正常。静脉注射甲基泼尼松龙治疗后，临床症状和肌酸激酶水平改善。
两例患者均表现为包括提上睑肌、眼外肌和颈后肌在内的非典型广泛炎症性肌炎，类似于重症肌无力（MG），但无 MG 相关抗体。依酚氯铵试验阴性，无每日波动。此前报道的两例病例也表现为累及眼外肌和面部肌肉的全身坏死性肌炎，由帕博利珠单抗引起。特发性炎症性肌炎引起的上睑提肌和眼外肌病变较为罕见，但免疫检查点抑制剂引起的肌炎可能更倾向于累及这些肌肉。本病例报告将提醒医生注意由帕博利珠单抗引起的、类似 MG 的、累及提上睑肌、眼外肌和颈后肌的全身性炎症性肌病的可能性。
