Clinical History:
The patient is a 65-year-old male with progressive lower extremity weakness. Over time he developed weakness in his grip strength. Lab results include negative Jo-1, HMGCR, and cN1A autoantibodies.
What are these vacuoles in this disease state?
A. Abnormal nuclear membranes
B. Abnormal autophagosomes
C. Accumulation of abnormal mitochondria
D. Accumulation of abnormal sarcomeres
Answer:
B. Abnormal autophagosomes
The patient suffers from sporadic inclusion body myositis (sIBM). While the anti-cN1A test was negative the sensitivity of this test for sIBM ranges from 33-89% thus a negative result does not rule out sIBM as a diagnostic possibility. While specificity is noted to be closer to 80%, we note that the specificity improves when the patient has a high positive result. The classic rimmed vacuoles of sIBM are believed to arise from accumulation of autophagosomes that are unable to fuse appropriately with lysosomes leading to inability of the autophagolysosomes to degrade proteins effectively. This is then thought to lead to cellular debris and toxic lysosomal enzymes accumulating and causing cellular damage. While abnormal mitochondria can accumulate in sIBM they are not the reason for rimmed vacuoles but rather can lead to red ragged fibers. While frozen artefact of nuclear membranes can mimic rimmed vacuoles, they are not true vacuoles.
Reference(s) / Additional Reading:
- Nur Azizah Allameen, et al. Inclusion body myositis and immunosenescence: current evidence and future perspectives, Rheumatology, Volume 64, Issue 3, March 2025, Pages 952–961, https://doi.org/10.1093/rheumatology/keae614
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