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Inflammatory myopathies and overlap syndromes: Update on histological and serological profile

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Abstract

The term ‘inflammatory myopathies’ (IMs) comprise a group of muscle diseases formed by four main categories known as polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Due to the increasing evidence of IMs over the course of different autoimmune diseases, the overlap myositis (OM) has been recently recognized as a possible stand-alone entity. IMs are characterized by a wide spectrum of autoantibodies, and the panel of myositis-associated autoantibodies (MAA) has dramatically increased over the last years giving the clinicians a further crucial support to differentiate the different types of myositis. This study aims to collect the most relevant evidence published up to date on the most commonly described OM with a particular emphasis on their histological aspects and also serological features.

Introduction

Inflammatory muscle diseases comprise a heterogeneous group of myopathies that may be classified into four main categories based on clinical and histological features: polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). The overlap myositis (OM), wherein polyarthritis, Raynaud's phenomenon and interstitial lung disease (ILD) are more commonly observed, has been recently recognized as a possible stand-alone category of inflammatory myopathies (IMs). This study aims to update on the diagnostic and classification criteria currently used for myositis as well as to describe in detail both histological and serological features of OM. Thus, we focused on the description of the most common forms of OM in the presence of the following autoimmune diseases: systemic sclerosis (SS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SjS) and rheumatoid arthritis (RA).

Section snippets

Myositis classification criteria

In the past years, several classification and diagnostic criteria (Table 1, Table 2, Table 3a/b) for IMs have been proposed; however, to date, a unanimous consensus has not been achieved. Those proposed by Bohan and Peter [1] in 1975 still represent the most commonly used criteria for inclusion in clinical trials. However, those criteria have been criticized for different reasons. First, they do not mention IBM because they predate its recognition as a separate condition; second, a loose

Dermatomyositis

Patients affected by DM typically manifest a subacute onset of disease, and inflammatory muscle involvement clinically arises with a symmetrical proximal muscle weakness [3]. Adult as well as childhood onset is described, with more prevalent extra-muscular manifestations in the juvenile form [3]. Cutaneous manifestation may accompany muscular symptoms or sometimes precede the onset of disease [3]. The lesions are photosensitive and the main skin signs of disease include periorbital heliotrope

Polymiositis

PM usually affects adults rather than children and it is clinically characterized by the presence of weakness of the proximal muscles usually developing subacutely over weeks or months. Because of its similarities with other myopathies, it should be considered as a diagnosis of exclusion. PM may occur alone or in association with other systemic autoimmune disorders, as described later. IBM, as well as IMNM and other conditions including toxic and endocrine myopathies, DM sine dermatitis and

Inclusion body myositis

IBM is considered the most common myopathy occurring in people over 50 years old. Men are more commonly affected than women and, from a clinical point of view, IBM can be distinguished from the other myopathies because of the presence of asymmetric weakness involving both proximal and distal muscles, with possible atrophy of the quadriceps and forearms [8]. IBM onset and evolution are quite subacute and patients might present normal or slightly elevated serum levels of enzymes (up to 10 times

Immune-mediated necrotizing myopathy

Necrotizing myopathies, in general, can be distinguished into two main categories: the IMNM and the non-immune-mediated myopathy (NIMNM). Different from the IMNM, the NIMNM might appear following medications or toxic exposure, and immunohistochemical (IHC) abnormalities are not typically observed [12]. IMNM occurs more frequently than PM, and the estimated overall prevalence among IMs is around 19% [13]. This type of myopathy has been described as possibly occurring in patients treated with

Myositis-specific autoantibodies

Positivity for serum autoantibodies characterize >80% of patients with PM and DM; serum autoantibodies can be divided into two different categories: the myositis-specific antibodies (MSA) and the myositis-associated antibodies (MAA) [15]. The target of such antibodies is wide including the most classically recognized aminoacyl-tRNA synthetase (ARS), the Mi-2 helicase/histone deacetylase protein complex and the signal recognition particle (SRP). In the past years, new targets have been proposed

Miopathies: differential diagnosis

In the case of patients with muscle symptoms and increased serum levels of muscle enzymes, one of the main challenges for clinicians is to exclude other possible causes of muscular sufferance not related to inflammatory myopathies. Indeed, the shared clinical and laboratory features between IMs and non-inflammatory myopathies (NIMs) are the frequent cause of diagnostic confusion. The main NIMs can be classified as follows: myotonic disorders (such as myotonic dystrophy type 1/type 2 or myotonia

Systemic sclerosis

As suggested by Pailk JJ et al., scleroderma myopathy represents a heterogeneous group of muscle disorders [31]. According to the study and the different criteria used for identifying patients with myopathy, the estimated frequency of this complication in SS is quite variable and reported between 14% and 96%. In a more recent meta-analysis, the prevalence of myositis over SS course was likely ∼13% [32].

From a histological point of view, two different subsets of patients may be identified

Summary

The available data on muscle pathology on different autoimmune diseases provide key information that gives us a better understanding of the possible pathogenic mechanisms driving these complications. However, the cases describing in detail the histology are still few and frequently analysed according to different methodologies. These elements do not allow reaching a unanimous consensus and definite conclusions. Non-specific findings are commonly described in all of the different forms of OM,

Disclosure

None to declare.

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