Clinical pearls and histopathological features help discriminate toxic rhabdomyolysis from immune-mediated necrotizing myopathy in statin-exposed patients

We have recently noted an increasing number of muscle biopsies performed to quickly rule out anti-HMGCR immune-mediated necrotizing myopathy (IMNM) in statin-treated patients with acute toxic rhabdomyolysis (TR). IMNM is a subacute to chronic progressive auto-immune myopathy diagnosed on clinical phenotype, serology and muscle biopsy, and TR is an acute potentially lethal condition usually diagnosed on clinical phenotype alone. Herein, we aimed to compare these muscle biopsies with a group of IMNM controls. Histopathological analysis of 36 biopsies from statin-exposed TR patients and 29 anti-HMGCR IMNM controls revealed overlapping morphologic patterns in 85 % of cases. Discriminating features highly suggestive of TR included predominance of 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 % TR and none of IMNM controls. Creatine kinase levels (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.