Zhou Yufan, Chen Jialin, Li Zunbo, Tan Song, Yan Chong, Luo Sushan, Zhou Lei, Song Jie, Huan Xiao, Wang Ying, Zhao Chongbo, Zeng Wenshuang, Xi Jianying
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Huashan Rare Disease Center, Huashan Hospital, Fudan University, Shanghai, China.
Front Neurol. 2022 Apr 8;13:879261. doi: 10.3389/fneur.2022.879261. eCollection 2022.
Antibodies to MuSK identify a rare subtype of myasthenia gravis (MuSK-MG). In western countries, the onset age of MuSK-MG peaks in the late 30's while it is unknown in Chinese population.
In this retrospective multicenter study, we screened 69 MuSK-MG patients from 2042 MG patients in five tertiary referral centers in China from October 2016 to October 2021 and summarized the clinical features and treatment outcomes. Then we subgrouped the patients into early-onset (<50 years old), late-onset (50-64 years old), and very-late-onset (≥65 years old) MG and compared the differences in weakness distribution, disease progression and treatment outcomes among three subgroups.
The patients with MuSK-MG were female-dominant (55/69) and their mean age at onset was 44.70 ± 15.84 years old, with a broad range of 17-81 years old. At disease onset, 29/69 patients were classified as MGFA Type IIb and the frequency of bulbar and extraocular involvement was 53.6 and 69.6%, respectively. There was no difference in weakness distribution. Compared with early-onset MuSK-MG, very-late-onset patients had a higher proportion of limb muscle involvement (12/15 vs.16/40, = 0.022) 3 months after onset. Six months after onset, more patients with bulbar (14/15 vs. 26/39, = 0.044) and respiratory involvement (6/15 vs. 0/13, = 0.013) were seen in very-late-onset than in late-onset subgroup. The very-late-onset subgroup had the highest frequency of limb weakness (86.7%, < 0.001). One year after onset, very-late-onset patients demonstrated a higher frequency of respiratory involvement than early-onset patients (4/12 vs. 2/35, = 0.036). 39/64 patients reached MSE. Among 46 patients who received rituximab, very-late-onset patients started earlier than late-onset patients [6 (5.5-7.5) vs. 18 (12-65) months, = 0.039], but no difference in the time and rate to achieving MSE was identified.
MuSK-MG patients usually manifested as acute onset and predominant bulbar and respiratory involvement with female dominance. Very-late-onset patients displayed an early involvement of limb, bulbar and respiratory muscles in the disease course, which might prompt their earlier use of rituximab. The majority MuSK-MG patients can benefit from rituximab treatment regardless of age at onset.
抗肌肉特异性激酶（MuSK）抗体可识别重症肌无力（MuSK-MG）的一种罕见亚型。在西方国家，MuSK-MG的发病年龄高峰在30多岁后期，而中国人群中的情况尚不清楚。
在这项回顾性多中心研究中，我们从2016年10月至2021年10月在中国五个三级转诊中心的2042例重症肌无力患者中筛选出69例MuSK-MG患者，并总结其临床特征和治疗结果。然后我们将患者分为早发型（<50岁）、晚发型（50-64岁）和极晚发型（≥65岁）重症肌无力，并比较三个亚组在肌无力分布、疾病进展和治疗结果方面的差异。
MuSK-MG患者以女性为主（55/69），平均发病年龄为44.70±15.84岁，范围为17-81岁。发病时，29/69例患者被分类为MGFA IIb型，延髓和眼外肌受累频率分别为53.6%和69.6%。肌无力分布无差异。与早发型MuSK-MG相比，极晚发型患者发病3个月后肢体肌肉受累比例更高（12/15 vs.16/40，P=0.022）。发病6个月后，极晚发型亚组中延髓（14/15 vs. 26/39，P=0.044）和呼吸肌受累患者比晚发型亚组更多（6/15 vs. 0/13，P=0.013）。极晚发型亚组肢体无力频率最高（86.7%，P<0.001）。发病1年后，极晚发型患者呼吸肌受累频率高于早发型患者（4/12 vs. 2/35，P=0.036）。64/69例患者达到最小症状改善（MSE）。在46例接受利妥昔单抗治疗的患者中，极晚发型患者开始治疗的时间早于晚发型患者[6（5.5-7.5）个月 vs. 18（12-65）个月，P=0.039]，但在达到MSE的时间和速率方面未发现差异。
MuSK-MG患者通常表现为急性起病，以延髓和呼吸肌受累为主，女性占优势。极晚发型患者在病程中早期出现肢体、延髓和呼吸肌受累，这可能促使他们更早使用利妥昔单抗。大多数MuSK-MG患者无论发病年龄如何，均可从利妥昔单抗治疗中获益。
