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.
Only few case reports and case series reported partial information about muscle histopathology in IMNM. Systematic review of literature or focused research on this field is still lacking. Furthermore, no studies analysed subgroups of IMNM exist in literature. Nevertheless a better characterization of muscle pathology for differential diagnosis with mimicking diseases for a specific diagnosis of IMNM is warranted. An early aggressive immunotherapy has been associated to better clinical outcome and lower residual disability.
In this context, this study will provide, by literature revision and deep muscle biopsy analysis, the needed elements for an early and reliable clinico-pathological diagnosis of IMNM regardless of serological profile. This project will lead to a better understanding of pathophysiological mechanisms of IMNM though muscle pathology analysis and possibly will allow to understand whether or not myopathological could differentiate among IMNM subgroups (HMGCR, SRP or seronegative).
Moreover we expect that systematic analysis of muscle histopathology could provide useful information for treatment strategies, possibly opening to novel immunotherapeutic approaches, based on specific and targetable immunohistochemical profile.