Myasthenia Gravis: A Disease of the Very Old

To the Editor: Myasthenia gravis (MG) is an autoimmune disease that may be severe and life threatening. It has been thought that MG onset after the age of 70 was exceptional,1 but several studies2, 3 have shown a progressive increase of MG in individuals aged 65 and older. As was reported in 2003,4 the incidence of MG increases from individuals aged 15 to 64 to those aged 65 and older. The causes of this high incidence with increasing age is felt to be a consequence of aging of the MG population and greater awareness of the disease,5 although it has also been suggested that there has been an increase in cases with late-onset MG.6 The senescence of the immune system could explain the presence of different or more autoimmune diseases in elderly adults.7 To verify previous results,4 the incidence and age distribution of MG onset over the following 10-year period was studied. The clinical course and response to therapy of young and elderly adults was compared. All individuals in the Osona County census (Barcelona, Spain) in whom MG was diagnosed between January 2001 and December 2010 were prospectively recruited. This area had a population of 142,337 inhabitants in the middle of the observational period (2005). Diagnosis of MG was based on clinical features, pharmacological testing (edrophonium test), and further corroborated according to an abnormal electrophysiological examination or detection of serum antiacetylcholine receptor or anti-muscle-specific receptor tyrosine kinase antibodies. The presence of other autoimmune phenomena was recorded. Clinical presentation was determined according to Myasthenia Gravis Foundation of America classification.8 Information on treatment was also obtained, and clinical changes for each individual were recorded. The occurrence of MG was calculated as the annual cumulative incidence during the 10-year study. Forty new MG cases were diagnosed over the 10-year study period, which corresponds to an annual incidence rate of 28.0 cases per million habitants (95% confidence interval = 19.3–36.7). Age of onset of MG ranged from 28 to 89 (median 74.1), with no difference in distribution according to sex (P = .61, Mann–Whitney U test). Figure 1 shows the incidence stratified according to sex and age. In the group aged 65 and older, the incidence increased each decade (49.8 × 106 aged 65–74, 157.64 × 106 aged 75–84, 170.89 × 106 aged ≥85). Antiacetylcholine receptor or anti-muscle-specific receptor tyrosine kinase antibodies were found in 87.5% of individuals with MG (13/14 < 65, 22/26 ≥ 65). There were no pretreatment statistical differences between Myasthenia Gravis Foundation of America classification and sex (P = .58, chi-square test) or age group (P = .41, chi-square test). Twelve individuals (30%) presented with other autoimmune phenomena (2/14, 14.2% <65; 10/26, 38.4% ≥65). Ten of the 40 patients died: one during the onset of the disease (myasthenia crisis) and nine of comorbid diseases not related to MG. Response to therapy was good for the other 30, and all improved with immunosuppressive treatment, if required. The maintenance dose of prednisone was 10 to 20 mg on alternate days for five of 18 aged 65 and older and 30 to 40 mg on alternate days for five of 12 younger than 65. Additional immunosuppressive drugs were required in three of the 18 (16.6%) elderly adults and in five of 12 (41.6%) younger than 65. This study found one of the highest MG incidences reported to date and shows that MG is increasingly frequent with age, with a striking incidence in elderly adults. Individuals aged 65 and older were more likely (38.4%) to have other associated immune-mediated diseases than younger individuals (14.2%). Elderly adults required lower maintenance corticosteroid doses than younger individuals with MG to achieve a good outcome. These results should raise awareness of physicians to include the diagnosis of MG when suggested by clinical signs, especially in very old people. Symptoms of MG, including ocular and generalized muscle weakness, fatigue, recurrent falls, and dysarthria or dysphagia, have a broad differential diagnosis in elderly adults,9, 10 and individuals may be misdiagnosed, particularly with stroke. Awareness of this high incidence of MG in elderly adults should help to decrease the number of underdiagnosed individuals with this treatable disease. We thank Dr. A. Arboix, Dr. E. Bufill, Dr. J. Monells, and Dr. A. Munmany, neurologists practicing in Osona County, who helped to identify incident patients, to collect their clinical data, and to link these data with pre-registered data. Conflict of Interest: The authors did not receive payment or services from a third party for any aspect of the submitted work except Dr. Illa, who received a grant (money to her institution from Spanish Health Research Agency (FIS-ISCIII Health Department; Intrasalud 2009/1964)). None had relevant financial activities or financial relationships outside the submitted work. Author Contributions: Aragonès and Illa conceived the study. Pont-Lluelles and Xandri conducted the field work, did statistical analysis and obtained the results. Aragonès and Roura-Poch contributed equally to this article. Alonso, Bolibar and Illa reviewed early and final manuscript versions. Sponsor's Role: None.