Abstract 22
Category: Clinical Science
At the end of the session, participants will be able to:
- Recognize histopathological and clinical features that can help discriminate immune from non-immune statin-induced myotoxicity
COI Disclosure:
None to disclose.
Benjamin Ellezam 1, Yves Troyanov 2, Océane Landon-Cardinal 3
1 Division of Pathology, CHU Sainte-Justine, 2 Division of Rheumatology, Hôpital du Sacré-Cœur, 3 Division of Rheumatology, Centre hospitalier de l’Université de Montréal; Université de Montréal, Montréal, QC.
Presenter
Dr. Ellezam completed a neuroscience PhD, MD, and anatomic pathology residency at Université de Montréal, followed by a
neuropathology fellowship at MD Anderson Cancer Center/Methodist Hospital and Texas Children’s Hospital in Houston.
Since 2012, he has served as staff neuropathologist at Sainte-Justine Hospital and associate clinical professor in the
Department of Pathology and Cell Biology at Université de Montréal. His practice focuses on neuromuscular pathology, with
more than 200 adult and pediatric muscle biopsies reviewed annually, and his research centers on myositis in mixed connective
tissue disease.
He founded and directs the Sainte-Justine Biobank for Research on Diseases of the Nervous System, whose scope was
recently expanded to include neuromuscular disorders and expected to include over 1,000 muscle biopsy specimens.
Target Audience:
Pathologists, Residents
CanMEDS:
Medical Expert (the integrating role)
Histopathological and clinical features can discriminate immune from non-immune statin-induced myotoxicity
Abstract
Anti-HMGCR immune-mediated necrotizing myopathy (IMNM) is a subacute to chronic progressive auto-immune myositis diagnosed on clinical phenotype, serology and muscle biopsy, and non-immune toxic rhabdomyolysis (TR) is an acute potentially lethal condition usually diagnosed on clinical phenotype alone. However, muscle biopsies are sometimes still performed in TR patients on statins to rapidly rule out IMNM, particularly when there is no quick access to serology results. Our objective was to describe histopathological and clinical features of TR patients and compare them with a group of IMNM controls. Out of 924 muscle biopsies received between 2019 and 2024 at our referral center, 36 biopsies from statin-exposed TR patients and 29 anti-HMGCR IMNM controls were identified. Histopathologic analysis revealed overlapping morphology in 85% of cases. Discriminating features highly suggestive of TR included predominance of pale acute necrotic fibers (p<0.001), groups of 4+ adjacent necrotic fibers (p<0.01), regenerative basophilic cuffs (p<0.001), and lack of LC3+ granular staining in non-necrotic fibers (p<0.001). Review of clinical data revealed acute creatinine elevation in 94% of TR patients and none of IMNM controls (p<0.001). Peak creatine kinase levels (CKs) > 25,000 IU/L were seen in 44% of TR and none of IMNM (p<0.0001). CKs normalized on average in 12 days (range 8-21) in TR and in >30 days in all IMNM cases. Although pathology can be discriminating, TR should be confirmed by following CKs closely over a few days without immunosuppression and muscle biopsy only performed to confirm IMNM in patients with persistently elevated CKs.