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Current Opinion in Rheumatology Nov 2021Necrotizing myopathy is a broad term. It includes patients with the recently described immune-mediated necrotizing myopathies (IMNM) who have specific antibodies, such... (Review)
Review
PURPOSE OF REVIEW
Necrotizing myopathy is a broad term. It includes patients with the recently described immune-mediated necrotizing myopathies (IMNM) who have specific antibodies, such as anti-hydroxy-3-methylglutaryl-CoA reductase or anti-signal recognition particle, seronegative phenotypes that can be associated with cancer, and other types of myositis and connective tissue diseases involving necrotic muscle fibers as a characteristic pathologic feature. Necrotizing myopathies that are not immune-mediated, such as those caused by drugs, dystrophies, infections, or even hypothyroidism are also included. The purpose of this review is to address the differential diagnosis of these disorders.
RECENT FINDINGS
New IMNM have been described over the last few years, some of them related with checkpoint inhibitors, drugs that are being increasingly used in cancer treatment. Necrotizing myopathy has also been reported in association with specific phenotypes and autoantibodies (e.g. anti-Mi2 dermatomyositis, antisynthetase syndrome, and myositis associated with antimitochondrial antibodies). Rarer cases associated with graft-versus-host disease and severe acute respiratory syndrome coronavirus 2 infection are also emerging.
SUMMARY
Differentiation between patients with IMNM and those without the superimposed autoimmune phenomena helps clinicians determine the best individualized approach to use and the appropriate immunosuppressive therapy, whenever needed.
Topics: Autoantibodies; Autoimmune Diseases; COVID-19; Diagnosis, Differential; Humans; Muscle, Skeletal; Muscular Diseases; Myositis; Necrosis; SARS-CoV-2
PubMed: 34482348
DOI: 10.1097/BOR.0000000000000836 -
Annual Review of Pathology Jan 2020Autophagy is an evolutionarily conserved catabolic process that targets different types of cytoplasmic cargo (such as bulk cytoplasm, damaged cellular organelles, and... (Review)
Review
Autophagy is an evolutionarily conserved catabolic process that targets different types of cytoplasmic cargo (such as bulk cytoplasm, damaged cellular organelles, and misfolded protein aggregates) for lysosomal degradation. Autophagy is activated in response to biological stress and also plays a critical role in the maintenance of normal cellular homeostasis; the latter function is particularly important for the integrity of postmitotic, metabolically active tissues, such as skeletal muscle. Through impairment of muscle homeostasis, autophagy dysfunction contributes to the pathogenesis of many different skeletal myopathies; the observed autophagy defects differ from disease to disease but have been shown to involve all steps of the autophagic cascade (from induction to lysosomal cargo degradation) and to impair both bulk and selective autophagy. To highlight the molecular and cellular mechanisms that are shared among different myopathies with deficient autophagy, these disorders are discussed based on the nature of the underlying autophagic defect rather than etiology or clinical presentation.
Topics: Animals; Autophagy; Humans; Lysosomes; Muscle, Skeletal; Muscular Diseases; Protein Aggregation, Pathological
PubMed: 31594457
DOI: 10.1146/annurev-pathmechdis-012419-032618 -
Current Opinion in Rheumatology Nov 2014This review discusses the spectrum of diseases associated with a necrotizing muscle biopsy. Although patients with toxic myopathies, endocrine dysfunction, and heritable... (Review)
Review
PURPOSE OF REVIEW
This review discusses the spectrum of diseases associated with a necrotizing muscle biopsy. Although patients with toxic myopathies, endocrine dysfunction, and heritable myopathies may have prominent necrosis on muscle biopsy, immune-mediated myopathies are emphasized here.
RECENT FINDINGS
A decade ago, immune-mediated necrotizing myopathy was recognized as a distinct form of myositis. Recent evidence now suggests that immune-mediated necrotizing myopathy is not one disease, but can be divided on the basis of the presence of distinct autoantibodies recognizing either the signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Anti-HMG-CoA reductase-positive patients can be further subdivided into those with and without statin exposure, the latter of which may be particularly refractory to immunosuppressive therapy.
SUMMARY
A significant number of patients with autoimmune myopathy have a predominantly necrotizing muscle biopsy with minimal lymphocytic infiltration. This biopsy finding occurs in various forms myositis, including the antisynthetase syndrome, scleroderma-associated myopathy, antisignal recognition particle-associated myopathy, statin-associated anti-HMG-CoA reductase-positive autoimmune myopathy, and statin-naïve anti-HMG-CoA reductase-positive myopathy. Future progress in elucidating pathogenic mechanisms and defining optimal treatment strategies may depend upon recognizing these distinct forms of myositis and analyzing them as separate entities.
Topics: Autoimmune Diseases; Humans; Muscle, Skeletal; Muscular Diseases
PubMed: 25203117
DOI: 10.1097/BOR.0000000000000106 -
Medecine Sciences : M/S Nov 2019
Review
Topics: Adult; Genetic Association Studies; Genetic Testing; Humans; Muscle, Skeletal; Muscular Diseases; Oxidative Stress; Oxidoreductases Acting on Sulfur Group Donors
PubMed: 31859631
DOI: 10.1051/medsci/2019183 -
The Veterinary Clinics of North... Apr 2024Boxelder and sycamore maple contain hypoglycin A (HGA), the toxic metabolite of which, MCPA-CoA, inhibits fatty acid β-oxidation, causing seasonal pasture myopathy... (Review)
Review
Boxelder and sycamore maple contain hypoglycin A (HGA), the toxic metabolite of which, MCPA-CoA, inhibits fatty acid β-oxidation, causing seasonal pasture myopathy (SPM) or atypical myopathy (AM), respectively. White snakeroot and rayless goldenrod contain multiple benzofuran ketones (BFKs). The identity/toxicity of BFKs appear variable, possibly involving interactions between toxins/toxic metabolites, but ultimately inhibit cellular energy metabolism. Unthrifty horses grazing sparse pastures during the fall appear predisposed to these plant-associated, frequently fatal, toxic myopathies. Toxidromes are characterized by varying degrees of rhabdomyolysis and cardiac myonecrosis, with plant toxins remaining toxic in hay and being excreted in milk.
Topics: Animals; Horses; Myotoxicity; Plant Poisoning; Horse Diseases; Plants, Toxic; Muscular Diseases
PubMed: 38151404
DOI: 10.1016/j.cveq.2023.11.001 -
Journal of Clinical Neuromuscular... Dec 2021This edition concentrates on inflammatory myopathies with reports of reclassification of polymyositis, cancer associations, evaluation of subclinical cardiac...
This edition concentrates on inflammatory myopathies with reports of reclassification of polymyositis, cancer associations, evaluation of subclinical cardiac involvement, myositis-specific and -associated antibodies, and immune checkpoint inhibitor myositis. A number of reports address sporadic late-onset nemaline myopathy and point out its diagnostic difficulty and the importance of identifying an associated monoclonal gammopathy that is likely of clinical significance and may warrant aggressive immunotherapy. Finally, treatment of nondystrophic channelopathies is addressed.
Topics: Humans; Immunologic Factors; Monoclonal Gammopathy of Undetermined Significance; Muscular Diseases; Myopathies, Nemaline; Myositis
PubMed: 34808649
DOI: 10.1097/CND.0000000000000387 -
Journal of Clinical Neuromuscular... Mar 2019We review the development of exon 51 skipping therapy with eteplirsen for Duchenne muscular dystrophy, including the recent report of long-term, sustained dystrophin... (Review)
Review
We review the development of exon 51 skipping therapy with eteplirsen for Duchenne muscular dystrophy, including the recent report of long-term, sustained dystrophin production. Studies of the late-life health profile of patients with Duchenne muscular dystrophy, early detection of left ventricular systolic dysfunction, and caregiver burden are also covered. A study of skeletal muscle magnetic resonance imaging in dysferlinopathies provides an extensive, detailed map of the involved muscles and consistency across phenotypes. Regarding the category of autoimmune myopathies, we discuss an article on the clinical and laboratory features associated with PM/Scl antibodies in comparison with other autoimmune myopathy subgroups. Finally, the overall increase in mortality in inflammatory myopathies is highlighted in a recent report from Sweden.
Topics: Autoantibodies; Humans; Medicine in Literature; Muscle, Skeletal; Muscular Diseases
PubMed: 30801483
DOI: 10.1097/CND.0000000000000226 -
Journal of Korean Medical Science Nov 2017
Topics: Arabinofuranosyluracil; Humans; Mitochondria; Mitochondrial Myopathies; Muscular Diseases
PubMed: 28960021
DOI: 10.3346/jkms.2017.32.11.1732 -
Practical Neurology Feb 2018Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle. Patients may present with indolent myopathic... (Review)
Review
Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle. Patients may present with indolent myopathic features, exercise intolerance or recurrent rhabdomyolysis. Diagnostic delays are common and clinicians need a high index of suspicion to recognise and differentiate metabolic myopathies from other conditions that present in a similar fashion. Standard laboratory tests may be normal or non-specific, particularly between symptomatic episodes. Targeted enzyme activity measurement and next-generation genetic sequencing are increasingly used. There are now specific enzyme replacement therapies available, and other metabolic strategies and gene therapies are undergoing clinical trials. Here, we discuss our approach to the adult patient with suspected metabolic myopathy. We outline key features in the history and examination and discuss some mimics of metabolic myopathies. We highlight some disorders of glycogen and fatty acid utilisation that present in adulthood and outline current recommendations on management.
Topics: Humans; Metabolic Diseases; Muscular Diseases
PubMed: 29223996
DOI: 10.1136/practneurol-2017-001708 -
Handbook of Clinical Neurology 2016Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle... (Review)
Review
Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle weakness, elevated muscle enzymes, myopathic findings on electromyography, and autoantibodies. DM patients are distinguished by their cutaneous manifestations. Characteristic features on muscle biopsy include the invasion of nonnecrotic muscle fibers by T cells in PM, perifascicular atrophy in DM, and myofiber necrosis without prominent inflammation in IMNM. Importantly, these are regarded as autoimmune diseases and most patients respond partially, if not completely, to immunosuppressive therapy. Patients with inclusion body myositis (IBM) usually present with the insidious onset of asymmetric weakness in distal muscles (e.g., wrist flexors, and distal finger flexors), often when more proximal muscle groups are relatively preserved. Although IBM muscle biopsies usually have focal invasion of myofibers by lymphocytes, the majority of IBM biopsies also include rimmed vacuoles. While most IBM patients do have autoantibodies, treatment with immunosuppressive agents does not improve their clinical course. Along with the presence of abnormally aggregated proteins on muscle biopsy, the refractory nature and relentless course of IBM suggest that the underlying pathophysiology may include a dominant myodegenerative component. This chapter will focus on the epidemiology, clinical presentation, and treatment of the autoimmune myopathies and IBM. An emphasis will be placed on recent advances, indicating that these are a diverse family of diseases and that each of more than a dozen myositis autoantibodies is associated with a distinct clinical phenotype.
Topics: Autoimmune Diseases; Humans; Immunosuppressive Agents; Muscular Diseases
PubMed: 27112692
DOI: 10.1016/B978-0-444-63432-0.00025-6