Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey

https://doi.org/10.1016/j.jns.2011.03.004Get rights and content

Abstract

Objective

To clarify the prevalence and clinical characteristics of myasthenia gravis (MG) in Japan.

Methods

We performed a nationwide epidemiological survey of MG in Japan. The clinical features were compared among five groups of patients, divided according to onset age. A generalized additive model (GAM) was used to assess the linearity of these relationships.

Results

A total of 8542 patients were reported, and detailed data were analyzed for 3141 patients. The estimated number of MG patients in Japan was 15,100, giving a prevalence of 11.8 per 100,000. Elderly-onset MG (≥ 65 years) accounted for 7.3% in 1987 (adjusted for population in 2005), but this had increased to 16.8% in 2006. Infantile-onset MG (0–4 years) accounted for 10.1% in 1987, and was still as high as 7.0% in 2006. The rate of ocular MG was highest (80.6%) in infantile-onset and lowest (26.4%) in early-onset disease, but the rate rose again in the late-onset group. GAM analysis of the ocular form showed a U-shaped curve, with a dip in the 20s. Anti-acetylcholine receptor antibodies were positive in only 50% of infantile-onset, but nearly 90% of elderly-onset patients. GAM analyses assessing the concurrence of thymoma and hyperplasia both showed reversed U-shapes, with peaks in the 50s and 20s–40s, respectively.

Conclusions

Persistent high incidence of infantile-onset disease and clinical heterogeneity according to onset age are characteristic features of MG in Japan.

Introduction

Myasthenia gravis (MG) is an autoimmune disease that targets neuromuscular junctions [1]. The disease is characterized by ocular symptoms, bulbar signs, weakness of the extremities, and respiratory failure. The clinical aspects of MG have changed drastically over the past few decades, reflected in decreased mortality [2], along with the discovery of antibodies against muscle-specific tyrosine kinase (MuSK) [3], and the use of immunosuppressants and intravenous immunoglobulin therapy (IVIG).

Several reports have indicated the existence of racial variations in MG, e.g., between patients of Caucasian and African origins. African patients present with a lower positivity for anti-acetylcholine receptor (AChR) antibodies, a higher positivity for anti-MuSK antibodies, and a more severe form of disease, compared with Caucasians [4]. A high frequency of juvenile-onset MG has been described in Asian countries [5], [6], [7], [8]; in China, 39–50% of all MG patients were reportedly children (< 15 years) [6], [7]. A high frequency of the ocular form is also a characteristic feature of MG in Asia, ranging from 47–73% [5], [6], [7].

An increasing incidence of late-onset or elderly-onset MG has been reported recently [9], [10], [11], [12]. This is a worldwide phenomenon, and is not confined to regional areas of Japan. The increase in late-onset MG has not yet been evaluated at a national level. However, this trend is important, because elderly patients suffer from various complications such as hypertension, diabetes mellitus, hyperlipidemia, stroke, cancer and osteoporosis, and the choice of appropriate therapeutic options can be challenging.

An increased prevalence of autoimmune diseases has been reported in Western developed countries [13], [14], [15]. This increase has been considered to be a result of environmental changes and improved medical care. It is therefore important to assess the changes in prevalence and clinical features of MG in Asian countries, which have undergone rapid environmental alterations. Japan is the only country in Asia where repeated nationwide epidemiological surveys have been carried out. The previous surveys were performed in 1973 [16], [17] and in 1987 [18]. Because it had been approximately 20 years since the last nationwide survey, we performed a third survey to determine the current epidemiological and clinical traits of MG in Japan.

Section snippets

Survey procedures

A nationwide MG survey was conducted by the Research Committees of Neuroimmunological Diseases and of Epidemiology of Intractable Diseases, sponsored by the Ministry of Health, Labour and Welfare, Japan. The study was approved by the Kyushu University Ethics Committee. The survey was carried out in two steps. First, a preliminary survey was undertaken to determine the prevalence and the approximate number of patients with MG in Japan, and a second survey was then conducted using a questionnaire

Estimated number of patients and prevalence rate

A total of 3919 institutions (72.2%) responded to the initial survey, reporting 8542 patients with MG. In the second questionnaire, detailed data were collected for 3141 patients, excluding 15 duplicate cases (36.9% of the preliminary survey). There were no significant regional differences in response rates. The estimated number of patients with MG was 15,100 (95% CI: 13,900–16,300), and the estimated prevalence rate was 11.8 per 100,000 (95% CI: 10.9–12.7). The number of MG patients more than

Discussion

This study was limited by the relatively low response rate to the second questionnaire (36.9%); this may have been partly due to the intricate nature of the questionnaire. However, clinical information was collected for 3141 patients (excluding the duplicates), which represents the largest sample size among the series of nationwide surveys of MG in Japan.

The estimated number of MG patients is steadily increasing along with its prevalence, and it had more than doubled at this survey, compared

Acknowledgments

The authors thank Dr. Tetsuro Konishi for providing helpful advice. This work was supported in part by grants from the Neuroimmunological Disease Research Committee and the Epidemiology of Intractable Diseases Research Committee from the Ministry of Health, Labour and Welfare, Japan.

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