By Dora Leung, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: This is a population-based study of inclusion body myositis (IBM) patients from a region of Sweden over a 33-year period. IBM presents later in life and has an unusual pattern of weakness with finger flexion, quadriceps, and swallowing muscles affected. Although it is described as an inflammatory myopathy, it does not respond to any immune-suppressive medications. It is a progressive disorder that reduces lifespan.
SOURCE: Lindgren U, Pullerits R, Lindberg C, Oldfors A. Epidemiology, survival, and clinical characteristics of inclusion body myositis. Ann Neurol 2022;92:201-212.
Inclusion body myositis (IBM) is a late-onset, slowly progressive weakness first described in 1971 with a distinct pattern of weakness. The most affected regions are finger flexion and knee extension. In addition to appropriate clinical features, the diagnosis is supported by pathology on muscle biopsy, which classically shows rimmed vacuoles with inclusions staining for amyloid. Unlike patients with other types of inflammatory myositis, patients with IBM tend to have poor clinical response to immunomodulatory therapies, with slow clinical decline.
There have been few population-based studies to determine the prevalence of the disease, ranging from 0.68/million in Turkey, to 182/million in Minnesota, using a combination of clinical features and muscle pathology for diagnostic criteria. The effect of IBM on survival has not been studied extensively, with small case series concluding that there is no effect or slight reduction in survival.
The authors of this study collected data from the Västra Götaland region in western Sweden with a total population of > 1.7 million in 2017. In the Swedish national healthcare system, information on all patients with neurologic diseases and any associated pathology studies are collected and stored at regional neurology and pathology departments, ensuring that all patients with an IBM diagnosis are captured for analysis.
The goal of the study was to identify all patients with a diagnosis of IBM living in the region between Jan. 1, 1985, and Dec. 31, 2017. Records were reviewed and data were collected up to June 30, 2018, or date of death, to include at least six months of clinical progress post-diagnosis. A total of 128 patients fulfilled the diagnostic criteria of definite IBM based on clinical findings and muscle pathology, with mean follow-up time of 8.0 years for all patients post-diagnosis, and 7.7 years for patients alive at the end of the study period.
Results of the study showed the prevalence of IBM in the Västra Götaland region of Sweden was 31.9/million (19/million women, 45/million men), and the incidence of the disease during the study period was 2.5/million/year. The mean age of onset for the 128 patients (30% women) was 64.4 years and the mean age of diagnosis was similar in both sexes at 69.5 years. Of the 73 affected patients who died during the study period, the survival rate after diagnosis averaged 13.8 years, with mean age of death 79.7 years, without a significant difference between men and women. For the same time period in that region, the expected age of death was, on average, 82 years for men and 85 years for women. The decline in cumulative survival rate starts about three years after diagnosis for women and about 13 years after diagnosis for men.
Regarding the effect of presenting symptom location on survival, the group with dysphagia had the shortest survival at 12.4 years, the group with finger flexion weakness as the first symptom had the longest survival at 15.1 years, and those who presented with quadriceps weakness had 13 years mean survival duration from symptom onset. By the time of death, 77% of the 73 patients required wheelchairs, reflecting high functional morbidity in this disease.
This study confirms that symptom onset tends to occur in an older population, with the mean age 64.4 years. The most common symptoms were quadriceps weakness and dysphagia, with the latter symptom more common in women. Dysphagia developed eventually in 77% of patients, with severe symptoms in about 25%. Those with severe dysphagia needed invasive interventions, such as myotomy and percutaneous endoscopic gastrostomy. About 8% (n = 10) of patients required respiratory support in the form of continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP); of the six who required BiPAP, four died within a year of use, suggesting that respiratory compromise occurs late in the disease. Various immune-modulating therapies were tried in these patients; no treatment was identified as beneficial at the group level.
Unlike some inflammatory myopathies, such as dermatomyositis, IBM patients do not have an increased risk of cancer compared with the general population. There may be a higher association with autoimmune disorders (21%, excluding myositis), but the comparison group used was the Danish population, which has a 5% reported rate of autoimmune disorders. The most common autoimmune disorder in the IBM patient group is hypothyroidism. The presence of anti-cN1A antibody in the disease also supports autoimmune etiology, since it is highly specific for the disease, although of unclear clinical or etiologic significance. In this study, of the 50 patients who were tested for the antibody, 40% had positive results. However, there was no difference in the clinical characteristics between the antibody-positive patients and those who tested negative, including age of onset, presenting symptoms, and frequency of dysphagia.
COMMENTARY
IBM is a rare inflammatory myopathy, with few epidemiologic studies of the disease, including its effect on survival. This is a large population-based study in a defined geographic region in western Sweden, with 128 patients identified over a 33-year period, and an average follow-up period of almost eight years. Although the sample size is relatively small, quadriceps weakness is the more common presenting complaint in men and dysphagia is the more common presenting complaint in women, although the latter symptom becomes much more prevalent over the course of disease.
This study shows that IBM decreases survival in patients, although it is unclear why the cumulative survival rate declines much earlier after diagnosis for women than men. Otherwise, there is no significant difference in the age of symptom onset or diagnosis between men and women. However, that may be the result of a small sample size in the study, further complicated by the fact that women constituted only 30% of patients.
