Clinical-pathologic classification of anti-HMGCR-positive immune-mediated necrotizing myopathy

Anti-HMGCR-positive immune-mediated necrotizing myopathy (IMNM), also anti-HMGCR myopathy, was initially considered as an exclusively skeletal muscular disease, observed in elderly patients with an acute onset. However, there is an increasing number of patients presenting greater clinical diversity than previously recognized. The aim of this study is to establish a comprehensive clinical-pathological classification for these patients, capturing the spectrum of disease presentations including both typical and atypical cases. We conducted a retrospective analysis and follow-up study of the clinical features, pathological manifestations, and treatment outcomes of 18 anti-HMGCR myopathy patients from Nanfang Hospital, along with data from 61 patients reported before. We defined 31 patients who presented with extra-muscular symptoms as overlap patients, while those who had merely muscular symptoms as non-overlap patients. Overlap patients had higher MMT-score, less muscular symptoms, specifically muscle weakness, and more extra-muscular symptoms, including ILD, arthralgia, weight loss and mostly skin involvement. Based on clinical, pathological, and genetic criteria, 12 peculiar patients were classified as MD-like patients. These cases, with earlier onset and longer duration, hardly had myalgia and extra-muscular symptoms, particularly skin involvement. Our study highlights the clinical and pathological heterogeneity of anti-HMGCR-positive IMNM. We identified a distinct subgroup of overlap patients, as well as MD-like patients. The classification system we proposed offers a practical framework for distinguishing these subtypes.