Background: Limb–girdle muscular dystrophy R2 (LGMD R2) is most frequently misdiagnosed as immune-mediated necrotizing myopathy (IMNM). This study aimed to compare the clinicopathological data of IMNM and LGMD R2 to find distinguishing features. Methods: We retrospectively reassessed the medical data of patients with IMNM (n = 41) and LGMD R2 (n = 8) treated at Tongji Hospital from January 2017 to December 2021. Results: In our cohort, patients with LGMD R2 had a longer interval of onset to first visit, mild muscle weakness with late upper limb involvement, less myalgia, no cervical muscle weakness or dysphagia, no extramuscular organs affected except cardiac involvement, and lack of various autoantibodies, such as antinuclear antibodies. These features were completely reversed in IMNM. Moreover, thigh MRIs showed that muscle edema prominently affecting the adductor magnus was a characteristic of IMNM, while extensive fatty replacement was more common in LGMD R2 (p = 0.0086). Necrotic myofibers presented in both entities (p = 0.1693), while features such as ring/whorled and splitting myofibers were more often found in LGMD R2 (p = 0.0112 and p < 0.0001, respectively). Conversely, sarcoplasmic p62 expression was more pronounced in IMNM (p < 0.05). There were 4 of 8 (50%) patients with LGMD R2 initially considered as seronegative IMNM, and therefore unnecessarily treated with immunosuppressive drugs. Insufficient recognition of the early clinical, imaging, and histopathological features of LGMD R2 is the main reason for misdiagnosis. Conclusions: These findings may help clinicians differentiate seronegative IMNM and LGMD R2, reducing early misdiagnosis and mismanagement. Particularly, prominent adductor magnus edema on MRI and abundant p62 staining seem to be good markers for IMNM, while the presence of splitting myofibers is a crucial clue to early hereditary myopathy, including LGMD R2.

BackgroundMuscle RING finger-1 (MuRF-1) plays a key role in the degradation of skeletal muscle proteins. We hypothesize the involvement of MuRF-1 in immune-mediated necrotizing myopathy (IMNM).MethodsMuscle biopsies from patients with IMNM (n = 37) were analyzed and compared to biopsies from patients with dermatomyositis (DM, n = 13), dysferlinopathy (n = 9) and controls (n = 7) using immunostaining.ResultsMuRF-1 staining could be observed in IMNM, DM and dysferlinopathy biopsies, whereas the percentage of MuRF-1 positive myofibers was significantly higher in IMNM than in dysferlinopathy (p = 0.0448), and positively correlated with muscle weakness and disease activity in IMNM and DM. Surprisingly, MuRF-1 staining predominantly presented in regenerating fibers but not in atrophic fibers. Moreover, MuRF-1-positive fibers tended to be distributed around necrotic myofibers and myofibers with sarcolemma membrane attack complex deposition. Abundant MuRF-1 expression in IMNM and DM was associated with rapid activation of myogenesis after muscle injury, whereas relatively low expression of MuRF-1 in dysferlinopathy may be attributed to damaged muscle regeneration.ConclusionsMuRF-1 accumulated in regenerating myofibers, which may contribute to muscle injury repair in IMNM and DM. MuRF-1 staining may help clinicians differentiate IMNM and dysferlinopathy.