Emerging atypical clinicopathological manifestations of immune-mediated necrotizing myopathy (IMNM).

Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy typically characterized by a subacute-onset, rapidly progressive proximal predominant weakness, markedly elevated creatine kinase (CK) levels, and myopathological features of necrotic and regenerating fibers with minimal or no lymphocytic infiltration. IMNM can be associated with anti-HMGCR and anti-SRP antibodies. Expediting a diagnosis and beginning treatment with immunotherapy is important as early treatment can improve patient symptoms and outcomes. Notably, recent evidence has revealed several atypical clinical and histopathologic phenotypes of IMNM, which can make recognizing this treatable disease challenging. There are reports of seropositive IMNM patients exhibiting a chronic and slowly progressive course of weakness, resembling limb-girdle muscular dystrophy, as well as isolated dysphagia, prominent oculobulbar involvement, or facioscapulohumeral muscular dystrophy-like phenotype. Some patients may present in presymptomatic stages with asymptomatic hyperCKemia. Myopathological findings of IMNM have also expanded to encompass features including tubular aggregates, myofibrillar pathology, mitochondrial myopathy, excessive lipid cumulation, and megaconial pathology. The aim of this review is to highlight these unusual clinical and histopathologic presentations of IMNM, as recognizing these atypical features of IMNM is crucial to expedite diagnosis, initiate appropriate immunotherapies, and improving prognosis in this treatable myopathy.