Classification, Diagnosis, and Management of Idiopathic Inflammatory Myopathies

Abstract

The detection and characterization of a large array of autoantibodies, including at least 8 different antisynthetase, anti-SRP, -200/100 (HMGCR), -Mi-2, -CADM-140 (MDA5), -SAE, -p155, -MJ (NXP-2), and -PMS1, frequently associated with distinct and well-defined clinicopathological features, allowed for significant improvement in the definition and diagnosis of idiopathic inflammatory myopathies (IIM). Classification remains difficult, with lingering divergence between the different specialties involved in IIM care, but several categories clearly stand out, including dermatomyositis (DM), overlap myositis (OM), polymyositis, necrotizing myositis, and sporadic inclusion body myositis (s-IBM). Biopsy and histological analysis remain crucial, particularly in the absence of autoantibodies, to accurately specify the diagnosis and rule out mimics such as muscular dystrophies and metabolic myopathies. Numerous infectious agents (in particular human immunodeficiency virus and human T cell lymphotrophic virus-1) and drugs (statins, tumor necrosis factor inhibitors, and proton pump inhibitors) can cause mimic IIM that must also be excluded. Pharmacological treatment, in addition to glucocorticoids and immunoglobulins, now includes mycophenolate mofetil and rituximab, which proved helpful in resistant cases, particularly rituximab in DM and OM. Exercise, initially seen as potentially deleterious, recently was shown to be efficacious and safe. IIM can thus be reasonably well controlled in most cases, although aggressive disease remains refractory to treatment, including some cases of necrotizing myopathy. Sporadic IBM still seems resistant to all medications tested to date.

Relevance of ultrasonography in assessing disease activity in patients with idiopathic inflammatory myopathies

“…1 The most frequent disorders in this group include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (s-IBM), overlap myositis (OM), necrotizing myositis and cancer-associated myositis (CAM). 1,2 Due to their low prevalence and wide variety of disease patterns, IIM are challenging to diagnose, treat and follow-up. 1,2 Several classification criteria of IIM have been developed over the years [3][4][5][6] but it remains difficult to create homogeneous criteria that fit all the group entities.…”

“…1,2 Due to their low prevalence and wide variety of disease patterns, IIM are challenging to diagnose, treat and follow-up. 1,2 Several classification criteria of IIM have been developed over the years [3][4][5][6] but it remains difficult to create homogeneous criteria that fit all the group entities. 2 Besides the problem in diagnosis, monitoring patients with IIM is also difficult as there is a lack of precise measures for assessing disease activity.…”

Interstitial lung disease in an adult patient with dermatomyositis and anti-NXP2 autoantibody

“…Some of these autoantibodies are frequently detected in patients with other connective diseases associated with myositis (especially systematic sclerosis) and are referred to as myositis-associated autoantibodies, whereas others are considered specific to IIMs and are referred to as myositis-specific antibodies (MSAs), including antibodies against aminoacyl transfer RNA (tRNA) synthetases, Mi-2 (a nuclear helicase) and the signal recognition particle [1,2]. MSAs, when present, contribute to the diagnosis of IIM, especially in patients with mild muscle involvement or with ILD pre-existing to the myositis, although other, nonspecific antibodies are associated with various frequencies of manifestations and distinct clinical phenotypes within the spectrum of IIM [1,2]. Novel targets of autoantibodies have recently been described in IIM patients without "classical" MSAs, including p155/140 (transcriptional intermediary factor (TIF)-1-γ), CADM-140 (melanoma differentiation-associated gene 5), small ubiquitin-like modifier activating enzyme (SAE)1 and SAE2, and nuclear matrix protein 2/MJ (NXP2) [3].…”

“…Accumulating evidence suggests an important contribution of autoimmune responses to the pathogenesis of these diseases. Autoantibodies are present in at least half of patients with IIMs [1]. Some of these autoantibodies are frequently detected in patients with other connective diseases associated with myositis (especially systematic sclerosis) and are referred to as myositis-associated autoantibodies, whereas others are considered specific to IIMs and are referred to as myositis-specific antibodies (MSAs), including antibodies against aminoacyl transfer RNA (tRNA) synthetases, Mi-2 (a nuclear helicase) and the signal recognition particle [1,2].…”

“…Autoantibodies are present in at least half of patients with IIMs [1]. Some of these autoantibodies are frequently detected in patients with other connective diseases associated with myositis (especially systematic sclerosis) and are referred to as myositis-associated autoantibodies, whereas others are considered specific to IIMs and are referred to as myositis-specific antibodies (MSAs), including antibodies against aminoacyl transfer RNA (tRNA) synthetases, Mi-2 (a nuclear helicase) and the signal recognition particle [1,2]. MSAs, when present, contribute to the diagnosis of IIM, especially in patients with mild muscle involvement or with ILD pre-existing to the myositis, although other, nonspecific antibodies are associated with various frequencies of manifestations and distinct clinical phenotypes within the spectrum of IIM [1,2].…”