接受免疫检查点抑制剂治疗患者的肌炎和重症肌无力特征：一项多中心回顾性队列研究
Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study.
作者信息
Plomp Lotta, Chassepot Hortense, Psimaras Dimitri, Maisonobe Thierry, Mensi Eric, Leonard-Louis Sarah, Plu Isabelle, Rozes Antoine, Tubach Florence, Touat Mehdi, Anquetil Celine, Wesner Nadege, Champtiaux Nicolas, Rigolet Aude, Demeret Sophie, Weiss Nicolas, Alyanakian Marie-Alexandra, Le Panse Rozen, Truffault Frédérique, Dragon-Durey Marie-Agnès, Chatenoud Lucienne, Abbar Baptiste, Bretagne Marie-Claire, Procureur Adrien, Similowski Thomas, Morelot-Panzini Capucine, Dres Martin, Ederhy Stephane, Benveniste Olivier, Salem Joe-Elie, Allenbach Yves
机构信息
Sorbonne University - AP-HP, Pitié-Salpêtrière Hospital, Department of Clinical Immunology and Internal Medicine, INSERM U974, Paris, France.
University of Picardie Jules Vernes - Amiens Picardie University Hospital, Department of Clinical Immunology and Internal Medicine, Amiens, France.
出版信息
Lancet Reg Health Eur. 2025 Jan 14;50:101192. doi: 10.1016/j.lanepe.2024.101192. eCollection 2025 Mar.
BACKGROUND
Immune checkpoint inhibitors (ICIs) may induce overlapping myositis/myasthenia gravis (MG) features, sparking current debate about pathophysiology and management of this emerging disease entity. We aimed to clarify whether ICI-induced (ir-) myositis and ir-MG represent distinct diseases or exist concurrently.
METHODS
We performed a retrospective multicenter cohort study. Using the Paris University Hospitals database (n = 2,910,417), we screened all patients with International Classification of Diseases codes or free text related to myositis/MG signs and ICI (n = 620). 'Ir-MG signs' were defined by fatigability, repetitive nerve stimulation (RNS) decrement, and/or acetylcholine receptor antibodies (AChR Abs).
FINDINGS
Ir-MG signs were never observed in the absence of ir-myositis (pathological diagnosis (n = 12/14) or CK levels >8000 U/L (n = 2/14)). Among ir-myositis patients, fatigability (2%; n = 1/62) and RNS decrement (2%; n = 1/41) were demonstrated only in one patient with pre-existing MG. AChR Abs testing yielded positive results in 26% of ir-myositis patients (n = 14/53). We revealed that test results were already positive prior to ICI therapy (n = 8/9). Clinically, ir-myositis frequently presented with "MG-like" oculomotor disease (50%; n = 31/62), bulbar dysfunction affecting speech (29%; n = 18/62) and swallowing (42%; n = 26/62), and respiratory disorders (53%; n = 33/62). Extraocular and diaphragm muscles necropsies disclosed intense muscle inflammation (100%; n = 5/5).
INTERPRETATION
In our extensive database, we found no evidence of isolated ir-MG, nor of clear neuromuscular junction dysfunction in ir-myositis. These findings suggest that patients with ir-MG suspicion frequently have ir-myositis and ir-MG might be rare. "MG-like" symptoms may stem from ir-myositis-specific predilection for oculo-bulbo-respiratory musculature. Indeed, we revealed florid inflammatory infiltration of the oculomotor and respiratory muscles. Additional studies are needed to confirm these results and to elucidate the role of pre-existing AChR Abs in ir-myositis.
FUNDING
None.
背景
免疫检查点抑制剂（ICI）可能诱发重叠性肌炎/重症肌无力（MG）特征，引发了关于这一新兴疾病实体的病理生理学和管理的当前争论。我们旨在阐明ICI诱导的（ir-）肌炎和ir-MG是代表不同疾病还是同时存在。
方法
我们进行了一项回顾性多中心队列研究。利用巴黎大学医院数据库（n = 2,910,417），我们筛选了所有具有国际疾病分类代码或与肌炎/MG体征及ICI相关的自由文本的患者（n = 620）。“ir-MG体征”由疲劳性、重复神经电刺激（RNS）递减和/或乙酰胆碱受体抗体（AChR Abs）定义。
结果
在没有ir-肌炎的情况下从未观察到ir-MG体征（病理诊断（n = 12/14）或肌酸激酶水平>8000 U/L（n = 2/14））。在ir-肌炎患者中，仅在一名既往有MG的患者中出现了疲劳性（2%；n = 1/62）和RNS递减（2%；n = 1/41）。AChR Abs检测在26%的ir-肌炎患者中呈阳性结果（n = 14/53）。我们发现检测结果在ICI治疗前就已经呈阳性（n = 8/9）。临床上，ir-肌炎常表现为“MG样”动眼神经疾病（50%；n = 31/62）、影响言语的延髓功能障碍（29%；n = 18/62）和吞咽功能障碍（42%；n = 26/62）以及呼吸障碍（53%；n = 33/62）。眼外肌和膈肌尸检显示有强烈的肌肉炎症（100%；n = 5/5）。
解读
在我们的广泛数据库中，我们没有发现孤立的ir-MG的证据，也没有发现ir-肌炎中有明确的神经肌肉接头功能障碍的证据。这些发现表明，怀疑有ir-MG的患者通常患有ir-肌炎，ir-MG可能很罕见。“MG样”症状可能源于ir-肌炎对眼-延髓-呼吸肌群的特异性偏好。事实上，我们发现动眼神经和呼吸肌有明显的炎症浸润。需要进一步的研究来证实这些结果，并阐明既往存在的AChR Abs在ir-肌炎中的作用。
资金
无。
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