Ricerc@Sapienza

Immune-mediated necrotizing myopathies (IMNMs) have been identified as emerging and separate entities among the idiopathic inflammatory myopathies (IIMs) during the past years. Many studies detailed three main different sub-entities:1) anti-SRP, 2) anti-HMGCR and seronegative IMNMs.
IMNMs are characterized by subacute, rapidly progressive muscular weakness, CK elevation and peculiar findings at muscle biopsy. IMNMs, with respect to other IIMs, usually present a more severe muscle impairment, rapidly progressing to fibro-fatty replacement of muscles that leads to a permanent muscular deficit. IMNMs are frequently refractory to conventional immunotherapy and most of patients requires aggressive immunotherapy to obtain a significant clinical improvement. Delayed aggressive treatment is associated to a worse clinical outcome and residual disability. Because of that, an early and specific diagnosis of IMNM is needed to promptly start a treatment to achieve the best clinical outcome.
Diagnosis of IMNM is mainly based on histopathological findings at muscle biopsy, consisting of prominent necrosis and regeneration of muscle fibers, with minimal or absent inflammatory infiltrates, variable MHC-I expression and complement deposition on non-necrotic fibers. Despite that, these histopathological features are non-specific findings, possibly mimicking other non-inflammatory myopathies. Moreover, the serological test for anti-SRP or anti-HMGRC antibodies may require time and supports the diagnosis only in positive patients.
For these reasons, better-defined histopathological findings in IMNMs are warranted for an early and specific diagnosis in this important subgroup of IIM.
The aim of this study is to re-define the myopathological and immunohistochemical features in a large cohort of IMNM patients, in order to identify the most sensitive and specific findings for an early and reliable diagnosis of IMNM based on muscle biopsy.