Inclusion body myositis: Update on the diagnostic and therapeutic landscape

Abstract

Inclusion body myositis (IBM) is a progressive muscle disease affecting patients over the age of 40, with distinctive clinical and histopathological features. The typical clinical phenotype is characterized by prominent involvement of deep finger flexors and quadriceps muscles. Less common presentations include isolated dysphagia, asymptomatic hyper-CKemia, and axial or limb weakness beyond the typical pattern. IBM is associated with marked morbidity as majority of patients eventually become wheelchair dependent with limited use of their hands and marked dysphagia. Furthermore, IBM mildly affects longevity with aspiration pneumonia and respiratory complications being the most common cause of death. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. These histopathological features are reflective of the complexity of underlying disease mechanisms. No pharmacological treatment is yet available for IBM. Monitoring for swallowing and respiratory complications, exercise, and addressing mobility issues are the mainstay of management. Further research is needed to better understand disease pathogenesis and identify novel therapeutic targets.

Keywords: aging; idiopathic inflammatory myopathies; inclusion body myositis; individualized medicine; neurodegenerative diseases.

Figure 1

Clinical findings in patients with inclusion body myositis. (A) Patient attempting to make a fist, demonstrating bilateral finger flexion weakness most severely affecting flexion at the distal interphalangeal joint, worse on the left side. (B) Same patient as in (A). Effacement of finger wrinkling over the palmar aspect of the interphalangeal joints, more pronounced on the left side, most noticeable over the distal interphalangeal joints. (C) Patient attempting knee extension, demonstrating bilateral quadriceps weakness, more severe on the left side where there is more noticeable thigh and leg muscle atrophy.

Figure 2

Frozen muscle sections from patients with inclusion body myositis. (A) H&E stain: inflammatory cells surrounding, and focally invading (arrow) muscle fibers. One muscle fiber (star) is completely split apart by inflammatory cells. (B) H&E stain: 3 adjacent muscle fibers harboring multiple vacuoles rimmed by a membranous material (example: arrow). (C) Congo Red stain viewed under Rhodamine optics: several fibers display one or more congophilic (bright red) inclusions (example: arrow). (D) Cytochrome C oxidase reaction: several fibers are devoid of enzyme reactivity (example: star).

Figure 3

Imaging findings in inclusion body myositis. (A–D) MRI of the thighs from a patient with IBM. Axial T1 images (A,C) showing a proximal-to-distal gradient, with preservation of proximal segments (A) and fatty infiltration of the distal vastus medialis and lateralis bilaterally (C), more pronounced in the right lower limb, with relative sparing of the rectus femoris (arrow). Axial T2 images (B,D) demonstrating sparing of the proximal segments of the quadriceps muscles (B), and only mild T2 hyperintensity surrounding areas of fatty infiltration distally (D). (E) Barium swallow demonstrating a cricopharyngeal bar with severe (more than 75%) luminal narrowing (circle).