Department of Medicine, Division of Immunology and Allergy, Lausanne University Hospital CHUV, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
Department of Neurology, Lausanne University Hospital CHUV, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.
J Immunother Cancer. 2018 Oct 22;6(1):110. doi: 10.1186/s40425-018-0429-4.
The prevalence of connective tissue disease (CTD) induced by immune checkpoint inhibitors (CPIs) in the absence of pre-existing autoimmunity is unknown.
We report the case of a melanoma patient treated for 8 months with pembrolizumab who developed a subacute ataxic sensory neuronopathy (SNN), including a right trigeminal neuropathy. Salivary gland biopsy showed inflammatory changes suggestive of Sjögren's syndrome, while brain MRI revealed enhancement of the right trigeminal ganglia. A high level of protein and pleocytosis was found in the cerebrospinal fluid, with negative cultures. Nerve conduction studies revealed the absence of sensory nerve action potentials in the upper and lower limbs and reduced motor responses in the upper limbs, fulfilling criteria for SNN. Blood tests revealed an important inflammatory syndrome, hemolytic anemia, elevation of total IgG levels and the presence of ANA autoantibodies specific to anti-SSA (52 and 60 kd). All these elements were absent before the initiation of the treatment with pembrolizumab. Initially, there was a clinical response following intravenous frontline methylprednisone, but the subacute relapse required the introduction of second-line treatment with intravenous immunoglobulins and then rituximab, which led to a quick clinical improvement.
Herein, we describe the first case of a patient who developed a typical SNN as a complication of severe neuro-Sjögren's syndrome induced by pembrolizumab treatment.
在没有自身免疫疾病的情况下，免疫检查点抑制剂（CPIs）引起的结缔组织病（CTD）的患病率尚不清楚。
我们报告了一例接受 pembrolizumab 治疗 8 个月的黑色素瘤患者发生亚急性共济失调感觉神经元病（SNN）的病例，包括右侧三叉神经神经病。唾液腺活检显示提示干燥综合征的炎症改变，而脑 MRI 显示右侧三叉神经节增强。脑脊液中蛋白和白细胞增多，培养阴性。神经传导研究显示上肢和下肢感觉神经动作电位缺失，上肢运动反应减弱，符合 SNN 的标准。血液检查显示存在严重的炎症综合征、溶血性贫血、总 IgG 水平升高和抗-SSA（52 和 60 kd）自身抗体阳性。所有这些元素在开始使用 pembrolizumab 治疗之前都不存在。最初，静脉注射一线甲基强的松龙后出现临床缓解，但亚急性复发需要引入二线治疗，包括静脉注射免疫球蛋白和利妥昔单抗，这导致了快速的临床改善。
在此，我们描述了首例患者在接受 pembrolizumab 治疗后发生严重神经干燥综合征引起的典型 SNN 的病例。
