The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases (collectively known as myositis) affecting the skeletal muscles as well as other organ systems such as ...skin, lungs, and joints. The primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and immune-mediated necrotizing myopathy (IMNM). Patients with these diseases experience progressive proximal muscle weakness, have characteristic muscle biopsy findings, and produce autoantibodies that are associated with unique clinical features. One distinguishing feature of these patients is that they are also known to have an increased risk of cancer. Since the first description of the association in 1916, it has been extensively reported in the medical literature. However, there have been significant variations between the different studies with regard to the degree of cancer risk in patients with IIM. These discrepancies can, in part, be attributed to differences in the definition of malignancy-associated myositis used in different studies. In recent years, significant advances have been made in defining specific features of IIM that are associated with the development of malignancy. One of these has been myositis-specific antibodies (MSAs), which are linked to distinct clinical phenotypes and categorize patients into groups with more homogeneous features. Indeed, patients with certain MSAs seem to be at particularly increased risk of malignancy. This review attempts a systematic evaluation of research regarding the association between malignancy and myositis.
Dermatomyositis (DM) and polymyositis (PM) are autoimmune myopathies characterized clinically by proximal muscle weakness, muscle inflammation, extramuscular manifestations, and frequently, the ...presence of autoantibodies. Although there is some overlap, DM and PM are separate diseases with different pathophysiological mechanisms. Furthermore, unique clinical phenotypes are associated with each of the myositis-specific autoantibodies (MSAs) associated with these disorders. This review will focus on the clinical features, pathology, and immunogenetics of PM and DM with an emphasis on the importance of autoantibodies in defining unique phenotypes and, perhaps, as clues to help elucidate the mechanisms of disease.
ABSTRACT
Statins are among the most commonly prescribed medications that significantly reduce cardiovascular risk in selected individuals. However, these drugs can also be associated with muscle ...symptoms ranging from mild myalgias to severe rhabdomyolysis. Although statin myotoxicity is usually self‐limited, in some instances statin‐exposed subjects can develop an autoimmune myopathy typically characterized by progressive weakness, muscle enzyme elevations, a necrotizing myopathy on muscle biopsy, and autoantibodies that recognize 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR), the pharmacologic target of statins. These antibodies are also found in some autoimmune myopathy patients without statin exposure. Importantly, anti‐HMGCR antibodies are not found in the vast majority of statin‐exposed subjects without autoimmune myopathy, including those with self‐limited statin intolerance. Thus, testing for these antibodies may help differentiate those with self‐limited statin myopathy who recover after statin discontinuation from those with a progressive statin‐associated autoimmune myopathy who typically require immunosuppressive therapy. Muscle Nerve 48: 477–483, 2013
The different autoimmune myopathies-for example, dermatomyositis, polymyositis, and immune-mediated necrotizing myopathies (IMNM)-have unique muscle biopsy findings, but they also share specific ...clinical features, such as proximal muscle weakness and elevated serum levels of muscle enzymes. Furthermore, around 60% of patients with autoimmune myopathy have been shown to have a myositis-specific autoantibody, each of which is associated with a distinct clinical phenotype. The typical clinical presentations of the autoimmune myopathies are reviewed here, and the different myositis-specific autoantibodies, including the anti-synthetase antibodies, dermatomyositis-associated antibodies, and IMNM-associated antibodies, are discussed in detail. This Review also focuses on a newly recognized form of IMNM that is associated with statin use and the production of autoantibodies that recognize 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the pharmacological target of statins. The contribution of interferon signaling to the development of dermatomyositis and the potential link between malignancies and the initiation of autoimmune myopathies are also assessed.
Inflammatory myopathies, collectively known as myositis, are heterogeneous disorders characterised by muscle inflammation, and frequently accompanied by extramuscular manifestations that affect the ...skin, lung, and joints. Patients with inflammatory myopathies were previously classified as having dermatomyositis if characteristic rashes accompanied the muscle involvement, and as having polymyositis if no rashes were present. Five main types of inflammatory myopathies are now widely recognised: dermatomyositis, immune-mediated necrotising myopathy, sporadic inclusion-body myositis, overlap myositis (including antisynthetase syndrome), and polymyositis. The discovery of autoantibodies that are specifically associated with characteristic clinical phenotypes has been instrumental to the understanding of inflammatory myopathies. Treatment is still largely based on expert opinion, but several studies have shown effectiveness of different therapies in various subsets of inflammatory myopathies. These advances will undoubtedly improve the outcomes of patients with inflammatory myopathies.
Immune-Mediated Necrotizing Myopathy Pinal-Fernandez, Iago; Casal-Dominguez, Maria; Mammen, Andrew L.
Current rheumatology reports,
04/2018, Letnik:
20, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by relatively severe proximal weakness, myofiber necrosis with minimal inflammatory cell ...infiltrate on muscle biopsy, and infrequent extra-muscular involvement. Here, we will review the characteristics of patients with IMNM.
Recent Findings
Anti-signal recognition particle (SRP) and anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies are closely associated with IMNM and define unique subtypes of patients. Importantly, the new European Neuromuscular Centre criteria recognize anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM as three distinct subtypes of IMNM. Anti-SRP myopathy patients have more severe muscle involvement, have more common extra-muscular features, and may respond best to immunosuppressive regimens that include rituximab. In contrast, anti-HMGCR myopathy is often associated with statin exposure and intravenous immunoglobulin treatment may be an effective treatment, even as monotherapy. Both anti-SRP and anti-HMGCR myopathy tend to be most severe in younger patients. Furthermore, children with these forms of IMNM may present with dystrophy-like features which are potentially reversible with immunosuppressant treatment. IMNM patients with either autoantibody may experience fatty replacement of muscle soon after disease onset, suggesting that intense and early immunosuppressant therapy may provide the best chance to avoid long-term disability.
Summary
IMNM is composed of anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM. Both anti-SRP and anti-HMGCR myopathy can cause severe weakness, especially in younger patients. Anti-SRP myopathy patients tend to have the most severe weakness and most prevalent extra-muscular features. Autoantibody-negative IMNM remains poorly described.
Although statins are generally safe and well tolerated, some patients experience muscle complaints that can be attributed to their use. Those with muscle discomfort but no demonstrable muscle ...weakness or creatine kinase (CK) elevations may have statin-associated muscle symptoms. Individuals with elevated CK levels, with or without muscle discomfort or weakness, may have statin-associated myotoxicity. Rare patients have statin-associated autoimmune myopathy, a disease characterized by proximal muscle weakness, elevated CK levels, and autoantibodies recognizing hydroxy-methyl-glutaryl coenzyme A reductase. In this review, the author provides the clinician with a practical approach to diagnosing and managing patients with each of these statin side effects.
•Three distinct subtypes of immune-mediated necrotizing myopathies are defined.•New pathological criteria for immune-mediated necrotizing myopathies are defined.•Anti-HMGCR myopathy, anti-SRP ...myopathy and antibody negative IMNM are defined.•Therapeutic recommendations for anti-HMGCR myopathy, anti-SRP myopathy are given.
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