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Idiopathic inflammatory myositis

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Abstract

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose.

A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings.

There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting.

Section snippets

Advances in diagnosis

The diagnosis of idiopathic inflammatory myopathy (IIM) has traditionally been based on a clinical presentation with skeletal muscle weakness, elevated serum levels of muscle enzymes including creatine kinase (CK) and the myopathic triad (fibrillations with sharp positive waves, polyphasic motor units with low amplitude and short duration and spontaneous high-frequency discharges) on electromyography together with characteristic histopathological changes on muscle biopsy. Antibodies, both

Antisynthetase antibodies

Aminoacyl transfer RNA (tRNA) synthetases (ARSs) are a group of cytoplasmic enzymes, each of which catalyse the binding of a specific amino acid to the cognate tRNA during protein synthesis. Antibodies directed to these enzymes (anti-ARS) interact with conformational epitopes in conserved regions of the enzyme to inhibit enzyme activity [2]. The anti-ARS are highly specific, can be detected preceding disease onset and are thus considered to be critical in disease pathogenesis [11].

Antibodies

cN1A antibody

Antibodies to cytoplasmic 5′-nucleotidase 1A (cN1A), a 43-kDa muscle autoantigen, have recently been identified in patients with IBM, supporting a role for B-cell-mediated humoral immunity in its pathogenesis [54], [55], ∗[56]. Anti-cN1A antibodies have high specificity for IBM, but they may also be found in patients with other autoimmune diseases, for example, systemic lupus erythematosus (SLE) or Sjögren's syndrome [54], ∗[56], [57], [58]. In a South Australian cohort of patients with

Myositis-associated antibodies

Antibodies to Ro52 are the most commonly detected MAAs [4], [39], and they have been found in the sera of 35/147 (23.8%) myositis patients from an Australian cohort [65], 30/155 (19%) patients from a French cohort [66], 30/100 (30%) Canadian patients [4] and 104/417 (25%) patients in a European cohort [39]. Importantly, when tested with Ro60 (SSA) by ELISA using a combination of the two antigens, up to 20% of anti-Ro52 antibodies are missed. As reactivity to Ro52 and Ro60 represents two

Muscle histopathology

A muscle biopsy is essential to confirming IIM, distinguishing between disease subsets and excluding other conditions. The cardinal histological feature common to DM, PM and IBM is mononuclear inflammatory cell infiltrate in skeletal muscle. These infiltrates consist of lymphocytes and macrophages within and/or around muscle fascicles and may invade muscle fibres [78]. Despite this unifying thread, distinct histopathological differences separate the subsets of IIM, reflecting underlying

Treatment of IIM

Therapeutic strategies for IIM have evolved over the years, particularly with the increasing availability of biologic agents, but they remain largely consensus driven rather than being based on randomised controlled trials. The rarity of these conditions, together with the varied classification criteria and outcome measures used, has made comparisons between trials difficult. More recent studies have incorporated better disease classification and IMACS core set measures.

The natural history and

Tools for research and future directions

IIM encompasses a heterogeneous group of disorders defined by clinical phenotype, serology and histology. The best approach to classifying IIM remains unclear. Universally accepted histopathological criteria are lacking, and a number of patients lack currently recognised MAA or MSA. Advances are being made in the development of clinico-serological and histologic classification, definitions of disease activity and damage and treatment strategies. As this occurs, longitudinal cohorts will be well

Summary

International collaborative efforts have made important advances in multiple facets of IIM. Increasing availability of testing for MSAs and MAAs have led to better definition of antibody profiles in patients with IIM and greater recognition of their clinical and prognostic significance. We now have a greater understanding of the correlations between MAAs and MSAs, histopathological findings and clinical subtypes. Moreover, there is increasing awareness of the association between antibody

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