In this study, we systematically reviewed 21 patients diagnosed with MuSK-MG in our center, and the detailed clinical characteristics including therapy and disease progression time were recorded. We evaluated the treatment response and the severity of disease by MGFA grade. Considering the significance of the long-term study of MuSK-MG, the present study provides a better understanding of musk-mg disease and its clinical course. Previous reports of the age of onset of MuSK-MG have varied considerably between ethnic groups. The onset age of MuSK-MG in Caucasians reported in European and American countries is mostly younger than 40 years[4], whereas in Asian the age of onset is generally after 40 years[6, 9, 10]. The mean age of onset of MuSK-MG in the present study was 51.86 ± 16.16 years, which was consistent with previous studies in Asian[10]. In contrast to the differential age of onset, MuSK-MG patients showed a similar female predominance (M:F = 4:17). Previous studies indicates the functions of oestrogen on enhancing B-cell production and promoting antibody secretion may be related to the gender ratio[11].
The initial muscle symptoms and the progression of MuSK-MG patients have been reported differently. A US study found that only 36% of patients with MuSK-MG started with ocular muscle symptoms and developed frequent crises early in the course of the disease, all of which progressed to a generalised form within 5 years[4]. Other studies revealed that MuSK-MG rarely starts as simple extraocular muscle weakness, with symptoms concentrated in the throat muscles[12]. In the present study, 48% of patients with MuSK-MG started with extraocular muscle weakness, and 100% patients progressed to other muscle groups in 4.38 ± 2.54 months, further confirming the risk of early progression to the generalised condition of MuSK-MG[13]. In addition, 6/21 patients suffered from myasthenic crises, as previous reported the crisis rates ranged from 25–48% in America[14]. Notably, 67% (4/6) of these patients have mild onset symptoms with a MGFA class of I before deterioration.
In recent years, several centers reported the clinical characteristics of MuSK patients (Table 4). These studies have shown that long-term AChE-I treatment in patients with MuSK-MG is first-line treatment in improving symptoms, with an effectiveness rate of 16%-75% in patients with Caucasian MuSK-MG, however there are significant individual differences in these effects[15]. The current study reports suggested that the improvement of symptoms and prognosis in MuSK MG patients depend on early and aggressive treatment and long-term maintenance, and that the combination of drugs is effective in controlling progression and improving symptoms of respiratory muscle weakness[16, 17]. As the most commonly AChE-I agent, pyridostigmine bromide was used in 17/21 (81.0%) MuSK-MG patients in our study, with 10/17(58.8%) patients showing symptomatic improvement. In this study, 16 patients were treated with corticosteroids in combination with AChE-I in the early stages and 56.3% of patients achieved long-term symptomatic stability or remission according to MGFA post-intervention status. Although 2 patients died of their disease, our experience indicated that, the application of corticosteroids appeared a certain effect on the disease deterioration. Similar results were published by Zhang et al, but Lavrnic et al reported MuSK positive patients in their center were all treated with corticosteroid drugs with a response rate of 47%[6, 18]. Furthermore, according to the drug dose at the last follow-up, low doses of pyridostigmine bromide and corticosteroids seems to be sufficiently for the symptomatic maintaining in MuSK-MG patients.
Table 4
Summary of relevant studies that focused on the clinical features and treatment of MuSKAb-positive patients
References | Country | Date | Number | Pyridostigmine therapy | CS therapy | Therapy response evaluation | Thymectomy | Follow-up | Status at the end of observation period |
Sanders, D B et al.[21] | USA | 2003 | 12 | 75% | ༞41.7% | ND | 58.3% | ND | ND |
Evoli, Amelia et al.[22] | Italy | 2003 | 37 | most | 81.1% | MGFA classification | 40.5% | At least 1 year | 3 CSR;4 PR;4 MM; 21 improved; 3 unchanged;2 died |
Lavrnic, D et al.[18] | Serbia | 2005 | 17 | most | 100% | ND | 52.9% | Yes | 11.8%CSR;23.5%PR; 29.4%improved; 23.6%unchanged; 11.7%died |
Lee, Jee-Young et al.[9] | Korea | 2006 | 4 | ND | 100% | MGFA classification | 25% | ND | 100%improved |
Ohta, K et al.[6] | Japan | 2007 | 23 | ND | 52.2% | MGFA classification | 13.0% | ND | 3 PR;6 improved; 3 unchanged |
Guptill, Jeffrey T et al.[4] | USA | 2010 | 110 | 98% | 92% | MGFA classification | 36% | 11 years for the Rome patient; 5.3 years for the Duke patients | 7.3%CSR;6.4%PR;40.4%MM, 37.6%improved; 7.3%unchanged;0.9%Worse |
Li, Mingqiang et al.[8] | China | 2018 | 2 | 100% | 100% | ND | 50% | ND | 50%MM;50% improved |
Zhang, Zunwei et al.[10] | China | 2020 | 14 | 57.1% | 100% | MGFA classification | ND | 11.8 ± 11.0 months | 7.7%CSR;23.1%PR; 53.8%improved;15.4%unchanged |
CS, corticosteroids; ND, not described; CSR, complete stable remission; PR, pharmacologic remission; MM, minimal manifestations |
In addition, tacrolimus performed in 6 patients and 4/6 patients adopted the drug as a maintain therapy at the last follow up. In consideration of the price and health insurance in local area, no patients in this study received rituximab. Compared with conventional treatment for MG, especially in refractory patients, the efficacy and safety of rituximab showed a probability of a favorable outcome[19]. Interestingly, two patients with a mild onset symptom chose herbal medicine as a long-term maintain therapy during the disease process. One patient received corticosteroids in the progression period, then chose to take herbal medicine when the symptoms were stable. At the last follow up, this patient kept herbal medicine therapy with a minimal manifestations condition and another patient was in complete stable remission. Thymectomy was performed in some MuSK patients (Table 3) and the outcome analyses failed to prove the efficacy of thymectomy for these patients. And the multicenter cohort also indicated thymectomy was not associated with additional clinical improvement of MuSK patients[20]. Although the mediastinum CT scan was examined as a common practice in our center, thymectomy was not recommended.
Most (85.7%) patients in this study had a long term follow-up (range 306–3762 days) and the status at the end of observation period showed a good result compared with previous studied[4, 18]. Two patients were treated with IVIg or plasma exchange while experiencing a MG crisis and received satisfied clinical results, suggests the importance of timely and feasible treatment in an urgent condition. Jeffrey et al. confirmed the clinical improvement of IVIg and plasma exchange and recommended that, the effect of plasma exchange is rapid and dramatic for acute exacerbations, comparing to IVIg[4]. However, two patients died during the period, which reminds these reasons such as elder, combined underlying diseases or physical condition may be factors in their poor prognosis, and classic therapy only has an effect on prolong the prognosis to some extent. The 9.5% mortality reminds MuSK MG is still intractable for physicians. Patients with refractory symptoms and unsatisfied responsive to classical treatment need considerate care and further exploration of effective therapy is urgent.