Abstract
This 10-year (1991 to 2000) prospective study of MG in the county of Osona (Barcelona, Spain) reveals an annual incidence rate of 21.27 cases per million inhabitants (95% CI 13.89 to 31.16). Incidence increased from 5.03 × 106 in the age group of 0 to 14 years to 14.68 × 106 in the age group of 15 to 64 years and to 63.38 × 106 in the older population. These results, the highest reported to date, may be explained by the population aging.
MG occurs at any age and in any sex and race, although it is classically accepted, as with other autoimmune diseases, that women around age 30 are the most commonly affected. The disease is considered infrequent over age 70.
According to studies performed during the last few years, when life expectancy has increased significantly, the incidence of MG has increased from 2 to 5 per million1,2⇓ to 9 to 14.7 per million inhabitants, specifically among patients with late-onset MG (older than 60 years).3-7⇓⇓⇓⇓
We performed a 10-year prospective population-based study to determine the incidence as well as the age distribution of current MG onset in a small county of Barcelona province, Spain. In this area, where the incidence of other neurologic diseases has been studied previously,8 life expectancy is 76 years for men and 82 years for women.
Methods.
We prospectively recruited the patients included in the census area of the county of Osona, in Barcelona province, Spain, whose MG symptoms began between January 1991 and December 2000. This area has a population of 122,923 inhabitants (60,358 men and 62,565 women) whose health care is covered mostly by the National Health System. For the recruitment and follow-up of the incident cases, all the neurologists (either public or private) in the area were involved as well as the neurologist from the hospitals of reference outside the area.
The diagnosis of MG was based on clinical features, neurologic examination, and pharmacologic test (Tensilon test), further corroborated by abnormal electrophysiologic examination (repetitive stimulation or single-fiber electromyogram study) or detection of serum anti-acetylcholine receptor (anti-AChR) antibodies. Six patients with probable MG were not included because although they fulfilled the clinical electrophysiologic criteria, the pharmacologic test did not show improvement of fatigability symptoms and the anti-AChR antibodies were negative.
For all patients, demographic data (sex, age at diagnosis), date of onset of disease and date of diagnosis, clinical presentation of MG, classification according to recommendations for clinical research standards,9 and presence of other autoimmune phenomena were recorded.
The occurrence of MG was calculated as the cumulative annual incidence during the 10-year fieldwork study. The number of inhabitants used for the denominators came from the census data of each year as the population in the area studied and the proportion of people older than 64 years increased progressively. The 95% CI for incidence rates and incidence ratios were calculated assuming that the observed number of cases was a sample drawn from a Poisson distribution and that the estimated incidence odds followed a binomial distribution. Test of significance for the comparison of incidence rates used approximate methods based on the normal distribution or the test for trend. Incidence rate ratios and 95% CI were calculated using the Mantel–Haenszel methods and tested adjusting for age. For the clinical description of incident cases, basic descriptive statistics were calculated and univariate statistical tests were applied, that is, Spearman correlation (r) or Kruskal–Wallis test for quantitative data and Fisher’s exact test for categorical data.
Results.
We found an annual incidence rate of 21.27 cases per million inhabitants (95% CI 13.89 to 31.16) as we detected 26 new MG cases over the 10-year study period. Sixteen patients were women and 10 were men, with an annual incidence rate of 25.74 (95% CI 9.14 to 25.98) × 106 women and 16.65 (4.80 to 18.39) × 106 men (table). The crude incidence ratio by sex was 1.55 (95% CI 0.66 to 3.81, p = 0.4). The age-specific incidence rate of MG increased markedly with each age group, from 5.03 × 106 in the age group of 0 to 14 years to 14.68 × 106 in the age group of 15 to 64 years and to 63.38 × 106 in the population of 65 or more years (p < 0.0001). This increase in the incidence by age was observed both in men and in women. At the same time, the incidence of MG was higher in women than in men for all age groups. The age-adjusted annual incidence rate ratio among women and men was 1.38 with a 95% CI of 0.63 to 3.04 (p = 0.5). The number of cases was too small to allow for a time trend analysis of the incidence rate.
Table 1 Number of cases and annual incidence rates of MG observed during 10-year (1991–2000) prospective study according to groups of sex and age
Anti-AChR antibodies were found in 61.5% of MG patients. Age at onset of MG ranged from 14 to 85 years with a median of 65 years, and there was a different distribution between sexes (figure). Median (range) age at onset for men was 66.5 (36 to 76) years, with 80% of cases occurring between the ages of 55 and 74 years. Women had a median age at onset of 58.5 (14 to 85) years (p = 0.4 for differences in relation to men) and presented a bimodal age distribution with 31.3% of cases occurring between 25 and 34 years and 50% of them from the age of 64 and older. Overall, 53.8% of all patients were older than 60 years, and 46.2% were 70 years or older.
Figure. Percentage distribution of the diagnosed cases of MG (from 1991 to 2000) by age group and sex. 
= men (n = 10); 
; = women (n = 16).
The interval of time between the onset of symptoms and the diagnosis of MG was <1 year in 65.4% of cases, 1 year in 23.1%, and 2 years in 7.7%; in only one male case, the diagnosis was delayed by 6 years. Early diagnosis, that is, within the year after the onset of symptoms, occurred in 75% of female cases but in 50% of male cases (p = 0.2). Patient age did not correlate with the time taken for diagnosis (r = −0.09, p = 0.8), either in men or in women. Maximum severity at the pretreatment state was distributed as follows: class I (n = 8) 30.8%, class IIA (IIa: n = 2; IIb: n = 3) 19.2%, class III (IIIa: n = 3; IIIb: n = 5) 30.8%, class IV (IVa: n = 1; IVb: n = 3) 15.4%, and class V (n = 1) 3.8%. There was no clear association between clinical classification and sex or age, nor there was a time pattern between the clinical classification and the year of diagnosis or the time to diagnosis.
Five patients (19.2%) presented other autoimmune phenomena. Vitiligo was found in four patients: alone in two patients, in combination with hypothyroidism in one patient, and combined with hypothyroidism and vitamin B12 deficit in another patient. One patient had hypothyroidism alone. These other autoimmune phenomena affected 18.8% of women and 20.0% of men. Patients with these other autoimmune phenomena had a median (range) age of 73.0 (32 to 85) years, whereas patients without these phenomena had a median age of 63.0 (14 to 81) years (p = 0.3). Thymoma was observed in one case.
Discussion.
We describe an annual incidence rate of MG of 21.27 per million, the highest reported to date. The study, performed prospectively over a period of 10 years on a relatively stable population of a small area in Barcelona province, Spain, indicates that the elderly contributed substantially to this incidence as 46.2% of the cases were patients over age 70.
Classically, studies have considered that <20% of patients experienced their first onset of the disease over age 60, and it has been considered exceptional over age 70.1,2⇓ However, more recent investigations have indicated a higher incidence of MG, due especially to an increase in late-onset cases, although their studies were performed either retrospectively or in larger populations, facts that make it difficult to estimate the real incidence in the population. For instance, retrospective studies4-6⇓⇓ found an annual incidence of 9.1 to 10.4 cases per million and a variation in the proportion of patients over the age of 60 from 36 to 59%. Finally, a prospective study in a large population found an incidence rate of 14.7 cases per million, with a 44.1% of patients over age 65, the highest incidence rate reported until now.7 Our results not only agree with the observation that MG increases markedly with increasing age but stresses the importance of the elderly in this incidence, as a considerable proportion of our patients experienced the initial disease onset over the age of 70 years. Our age-specific incidence rate in the elderly population reached 63.38 cases per million inhabitants per year compared with the 14.68 in the younger population. Although we applied a close surveillance of all possible incident cases of MG, the use of strict criteria to confirm the disease, the possibility of dropping patients cared for in distant health centers, and the need for some clinical course to suspect the disease made us discard an incidence overestimation. We also do not have arguments against an extrapolation of our results to other populations. Our high observed incidence rate of MG was not only of ocular forms of the disease, as 69.2% of our case series had generalized MG. Myasthenia type I reached 30.8%, whereas it varied from 20 to 46% in the cases described by other authors.5,7⇓
The percentage of patients with thymoma was low, as this diagnosis was made in only one case in this series. It is possible that the high frequency of elderly patients in our study contributed to this finding, as other series in which old patients were included also found a low incidence of thymoma.6
The group of patients with other autoimmune phenomena tended to have a median age higher than those patients without. In fact, three of the five patients with other autoimmune diseases were among the group of late-onset MG (over age 70). These results agree with the hypothesis of a paradoxical increase in autoimmunity in the elderly.10
Acknowledgments
Acknowledgment
The authors thank Drs. Arboix, J.M. Espadaler, J. Monells, and I. Royo for their contribution to the data, Drs. A. Pou–Serradell, J. Brugués, and J. Vilaró for their support during all the years of the study, and Dr. E. Thompson for her help in editing the earlier drafts.
- Received August 8, 2002.
- Accepted November 18, 2002.
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