Inclusion body myositis with early onset: a population-based study

Abstract

Introduction: Inclusion body myositis (IBM), an inflammatory myopathy with progressive weakness without efficient treatment, typically presents after 45 years of age and younger patients are sparsely studied.

Methods: In a population-based study during a 33-year period, 142 patients with IBM were identified in western Sweden. Six patients fell outside the European Neuromuscular Centre 2011 criteria for IBM due to young age at symptom onset, verified by a muscle biopsy < 50 years of age. These were defined as early-onset IBM and included in this study. Medical records, muscle strength, comorbidities, muscle biopsies, and nuclear- and mitochondrial DNA were examined and compared with patients with IBM and age matched controls from the same population.

Results: The median age at symptom onset was 36 (range 34-45) years and at diagnosis 43 (range 38-58) years. Four patients were deceased at a median age of 59 (range 50-75) years. The median survival from diagnosis was 14 (range 10-18) years. The prevalence December 31 2017 was 1.2 per million inhabitants and the mean incidence 0.12 patients per million inhabitants and year. The mean decline in quadriceps strength ± 1 standard deviation was 1.21 ± 0.2 Newton or 0.91 ± 0.2% per month and correlated to time from diagnosis (p < 0.001). Five patients had swallowing difficulties. All patients displayed mitochondrial changes in muscle including cytochrome c oxidase deficiency and the mitochondrial DNA mutation load was high.

Conclusions: Early-onset IBM is a severe disease, causing progressive muscle weakness, high muscle mitochondrial DNA mutation load and a reduced cumulative survival in young and middle-aged individuals.

Keywords: Epidemiology; Inclusion body myositis; Inflammatory myopathy; Mitochondrial DNA; Muscular weakness.

Fig. 1

Survival in IBM. A Life table estimate of observed cumulative survival in early-onset IBM, clinicopathological IBM, and matched controls. The number above the x-axis shows the mean number of patients with early-onset IBM at risk per year. The number of controls for patients with early-onset IBM varied from 6081 to 11,406 depending on age and year. B Age at death in patients with early-onset IBM and clinicopathological IBM in VGR, Sweden. EO early-onset IBM, CLP clinicopathological IBM

Fig. 2

Development of knee extension weakness in individual patients over time from diagnosis. A Absolute strength in Newton (N) range ± 1SD − 0.11 ± 0.10 N to − 3.4 ± 0.31 N per month. B Strength as % of the first available measurement range ± 1SD − 0.32 ± 0.15% to − 1.6 ± 0.14% per month. EO early-onset IBM, SD standard deviation

Fig. 3

Morphological and mtDNA changes in early-onset IBM. A, B Hematoxylin and eosin staining shows inflammatory cell infiltrates (arrows), invasion of non-necrotic muscle fibers (arrowhead) and a fiber with rimmed vacuoles (asterisk). C, D There are numerous COX-deficient fibers, which appear blue (arrows) in cytochrome c oxidase/succinate dehydrogenase (COX/SDH) staining. E, F Circular map of muscular mtDNA in early-onset IBM with location of duplications (red) and deletions (blue). Higher color intensity relates to higher frequency of each rearrangement. Multiple rearrangements with different locations are present in the patients. Most deletions are located to the major arc between OH (origin of heavy strand replication) and OL (origin of light strand replication). A, C, E Muscle biopsy from the vastus lateralis muscle of patient EO1 at age 41 years, scale bar 250 μm. B, D, F Muscle biopsy from the vastus lateralis muscle of patient EO5 at age 53 years, scale bar 100 μm. G, H Mitochondrial DNA mutation load and mtDNA copy number in early-onset IBM, clinicopathological IBM and normal controls. The horizontal lines represent the median values. EO early-onset IBM, CLP clinicopathological IBM. **p = 0.0079, ***p = 0.0004, ****p < 0.0001